title: Hemostatic Disorders in Feline Immunodeficiency Virus‐Seropositive Cats

text: The hemostatic function of 40 feline immunodeficiency virus (FlV) seropositive and 8 FIV and feline leukemia virus (FeLV) seropositive cats was evaluated and compared with reference values from 30 clinically healthy cats. The FIVpositive cats were divided into 3 groups: group I included asymptomatic carriers; group II comprised sick FIV‐infected cats with illnesses not likely to influence the hemostatic system; and group III included FIV‐positive cats with diseases potentially associated with coagulopathies. Platelet counts in FIV/FeLV‐infected cats were significantly lower than in healthy cats (P < .003), whereas the differences in the 3 groups of FIV‐positive cats were variable (group I, P= .009; II, P= .05; III, P= .09). Thrombocytopenia (< 145,000 platelets/μL) was present in 4 FIV‐positive and 3 FIV/FeLV‐positive cats. Platelet aggregation induced by collagen (0.5 and 0.25 μg/mL), adenosine diphosphate (ADP) (1 and 0.6 μmol/L), and thrombin (0.4 and 0.25 IU/mL) was not significantly different from that of healthy cats. The plasma coagulation system was evaluated by measuring one‐stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration, coagulation factor assays, fibrinogen and fibrin degradation products (FDP), and plasma exchange test. The OSPT was similar in FlV‐seropositive cats and in the healthy control group. Cats with FIV infection, however, had markedly shorter clotting times than healthy cats when using a modified test system (P < .05). In all groups of FIV‐infected cats and in those with FIV/FeLV infection, APTT measured with 2 different commercially available tests, and a modified plasma assay was markedly prolonged compared with healthy cats (APTT1 and 2:3 modification: P < .01; APTT2: P < .05 except group III). In 22 of 40 cats with FIV and in 5 of 8 cats with FIV/FeLV infection, plasma samples were beyond the reference range. The thrombin time was also significantly prolonged in cats with FIV and FIV/FeLV infection (P < .01); values in 17 of 40 FIV‐positive cats were above reference range. The mean fibrinogen concentration of cats with FIV and FIV/FeLV infection was higher than in the healthy control group (P < .001). Factor VIII activity of 4 cats with FIV infection was 1.5 times higher than that of healthy cats. Factor XII activity of 3 cats from a group of 20 cats with prolonged APTT was between 20% and 35%. Factor IX and XI activities ranged between 70% and 120%. The markedly prolonged APTT in 2 FIV‐positive cats could be shortened considerably in a plasma exchange test using 20% feline pooled plasma. The alterations in the coagulogram of FIV‐seropositive cats were not related to a clinical stage or concurrent diseases. A definite explanation of the distinct disorder within the intrinsic plasma coagulation system in FIV‐infected cats was not found.


title: Expression and distribution of cystic fibrosis transmembrane conductance regulator in neurons of the spinal cord

text: To verify the hypothesis that cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in neurons of the human spinal cord, we investigated the presence and distribution of CFTR protein and mRNA in different segments of the human spinal cord obtained from autopsies. The techniques employed included reverse transcriptase‐polymerase chain reaction (RT‐PCR) to detect CFTR gene expression, in situ hybridization to detect mRNA distribution, and immunohistochemistry to detect protein distribution. The specificity of these experiments was established with extensive controls. We found widespread and abundant expression of CFTR in neurons of the human spinal cord. CFTR protein and mRNA are localized to the cytoplasm of neurons in all segments of the spinal cord but not to glial fibrillary acidic protein (GFAP)‐positive cells. CFTR is a very important molecule, acting as a chloride channel and regulating many physiological functions, including salt transport, fluid flow, and intracellular ion concentrations. Its mutation causes cystic fibrosis. Our finding of abundant CFTR in the spinal cord suggests that this molecule may be significant in the normal function and pathology of the spinal cord. © 2009 Wiley‐Liss, Inc.


title: CD13 mediates phagocytosis in human monocytic cells

text: CD13 is a membrane‐bound ectopeptidase, highly expressed on monocytes, macrophages, and dendritic cells. CD13 is involved in diverse functions, including degradation of peptide mediators, cellular adhesion, migration, viral endocytosis, signaling, and positive modulation of phagocytosis mediated by FcγRs and other phagocytic receptors. In this work, we explored whether besides acting as an accessory receptor, CD13 by itself is a primary phagocytic receptor. We found that hCD13 mediates efficient phagocytosis of large particles (erythrocytes) modified so as to interact with the cell only through CD13 in human macrophages and THP‐1 monocytic cells. The extent of this phagocytosis is comparable with the phagocytosis mediated through the canonical phagocytic receptor FcγRI. Furthermore, we demonstrated that hCD13 expression in the nonphagocytic cell line HEK293 is sufficient to enable these cells to internalize particles bound through hCD13. CD13‐mediated phagocytosis is independent of other phagocytic receptors, as it occurs in the absence of FcγRs, CR3, and most phagocytic receptors. Phagocytosis through CD13 is independent of its enzymatic activity but is dependent on actin rearrangement and activation of PI3K and is partially dependent on Syk activation. Moreover, the cross‐linking of CD13 with antibodies rapidly induced pSyk in human macrophages. Finally, we observed that antibody‐mediated cross‐linking of hCD13, expressed in the murine macrophage‐like J774 cell line, induces production of ROS. These results demonstrate that CD13 is a fully competent phagocytic receptor capable of mediating internalization of large particles.


Acute Tubulointerstitial Nephritis With Eosinophiluria in a Dog


title: H(v)1 Proton Channels in Dinoflagellates: Not Just for Bioluminescence?

text: Bioluminescence in dinoflagellates is controlled by H(V)1 proton channels. Database searches of dinoflagellate transcriptomes and genomes yielded hits with sequence features diagnostic of all confirmed H(V)1, and show that H(V)1 is widely distributed in the dinoflagellate phylogeny including the basal species Oxyrrhis marina. Multiple sequence alignments followed by phylogenetic analysis revealed three major subfamilies of H(V)1 that do not correlate with presence of theca, autotrophy, geographic location, or bioluminescence. These data suggest that most dinoflagellates express a H(V)1 which has a function separate from bioluminescence. Sequence evidence also suggests that dinoflagellates can contain more than one H(V)1 gene.


European College of Veterinary Internal Medicine‐Companion Animals: Oral Research Communications of the 18th ECVIM‐CA Congress Ghent, Belgium, 4th to 6th September 2008


Speakers Abstracts


title: Detection of Human Rhinoviruses and Their Molecular Relationship Using cDNA Probes

text: We describe here a cDNA: RNA hybridization system for the study of human rhinoviruses. We have constructed an M13 probe from the 5′ end of the genome of rhinovirus 14 (HRV‐14) and used this to detect directly viral RNA. Of the 56 human rhinoviruses so far investigated 54 or 96.4% gave clearly positive hybridization signals. However, the strength of this signal depended very much on the molecular relationship of these viruses. Thus, HRV‐3, 4, 17, 72, and, to a slightly lesser extent, HRV‐2, 6, 9, 13, 19, 31, 42, 49, 64, and 69 appear to be closely related to HRV‐14 whereas HRV‐5, 7, 8, 16, 32, 40, 45, 55, 56, 63, 80, 82, and 85 appear to be relatively divergent. Further, evidence is provided in this study that indicates that it would be feasible to use cDNA probes to detect human rhinoviruses in nasal washings. However, the sensitivity of detection was clearly affected by both the inclusion of inhibitors of endogenous RNase activity in the RNA extraction mixture and also in the method of extracting the viral RNA. From reconstruction experiments in nasal washings and under optimal conditions, we can detect virus at 10(2.8) TCID(50)/ml.


The safety of Bacillus species as insect vector control agents


title: Introducing a Senior Course on Catastrophe Preparedness into the Dental School Curriculum

text: This article describes an integrated fourth‐year course in catastrophe preparedness for students at the New York University College of Dentistry (NYUCD). The curriculum is built around the competencies proposed in “Predoctoral Dental School Curriculum for Catastrophe Preparedness,” published in the August 2004 Journal of Dental Education. We highlight our experience developing the program and offer suggestions to other dental schools considering adding bioterrorism studies to their curriculum.


title: Serotonin turnover rate in raphe and cortex of mice infected with Venezuelan equine encephalomyelitis virus

text: The turnover of serotonin (5HT) was determined in the raphe area and cortex of mice infected with Pixuna, a strain of intermediate virulence of Venezuelan equine encephalomyelitis virus (VEEV). NMRI‐mice, 24 days old, were inoculated intracerebrally (ic) with 300 LDS0 of the virus. The animals were sacrificed 4, 7, 15, 21, 30, and 60 days postinoculation. 5HT and 5‐hydrodryindolacetic acid (SHIAA) in raphe and cortex were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Turnover rate of 5HT was determined by the administration of pargyline, p‐chlorophenylalanine, and probenecid. The content of 5HT or SHIAA and 5HT/5HIAA ratios were not significantly different in infected compared with control mice. However, a decrease of 5HT turnover rate, determined after pargyline treatment, was observed in the raphe and not in the cortex of infected mice at 4 and 7 days after the inoculation. The turnover rate/(5HT)(0) in raphe is decreased in infected mice with signs of illness, suggesting a lower density of 5HT innervation in this brain area. The administration of p‐chlorophenylalanine and probenecid showed that the cortex is also affected, but the synthesis is less modified than metabolism or elimination. Cell bodies of 5HT neurons seem to be more susceptible than projections to infection by Pixuna strain of VEEV.


COMPILED BY THE VACCINATION GUIDELINES GROUP (VGG) OF THE WORLD SMALL ANIMAL VETERINARY ASSOCIATION (WSAVA)


title: Attitudes Toward People Living With HIV/AIDS: A Model of Attitudes to Illness

text: This study examined attitudes toward people living with HIV/AIDS within a sample of 220 young men and women. As predicted, a multiple regression analysis revealed that the fear of contracting HIV/AIDS through casual contact was a significant predictor of both men's and women's willingness to interact with people living with HIV/AIDS. Attitudes toward homosexuality were also a significant predictor of attitudes toward people living with HIV/AIDS among women, who generally have a low risk of contracting the disease in Western societies. These results indicate that attitudes toward people with a serious illness may be strongly related to the perceived risk of contracting the disease.


title: Blastogenesis of Large Granular Lymphocytes in Nonlymphoid Organs

text: High numbers of large granular lymphocytes (LGL) accumulate in the livers and peritoneal cavities of mice during the course of viral infection. Accumulation of natural killer (NK) cells at day 3 postinfection (p.i.) was shown to be radiation‐sensitive, implying that proliferation was required for this response. Accumulation occurred in splenectomized mice, indicating that the spleen, known to be an organ for mature NK cell proliferation, was not the major source for liver and peritoneal NK/LGL. Significant percentages (> 25%) of the LGL found in the liver and peritoneal cavity following viral infection or interferon induction with poly‐inosinic:pory‐cytidylic acid were defined morphologically as blasts (large cells with prominent nucleoli and intensely basophilic cytoplasms containing azurophilic granules). Most blast LGL at day 3 p.i. were sensitive to administration of anti‐asialo GM(1) serum in vivo, were Lyt‐2(‐), and were enriched in populations that lysed NK cell‐sensitive targets in vitro, indicating that these were NK/LGL. At day 3 p.i., leukocytes from the liver and peritoneal cavity incorporated (3)H‐thymidine and bound to and killed NK cell‐sensitive targets in single‐cell cytotoxicity assays. These data suggest that NK/LGL undergo at least one round of division in the liver and peritoneal cavity during viral infection. In contrast, blast LGL at day 7 p.i. were resistant to in vivo treatments with anti‐asialo GM(1) serum, were Lyt‐2(+), and were enriched in populations of cells that killed virus‐infected histocompatible targets, indicating that they were cytotoxic T lymphocytes (CTL). These results suggest that both NK/LGL and CTL/LGL are capable of blastogenesis and presumed proliferation at sites of virus infection, providing a means for the in situ augmentation of a host's cell‐mediated antiviral defenses.


title: Effect of persistent mouse hepatitis virus infection on MHC Class I expression in murine astrocytes

text: Neurotropic strains of mouse hepatitis virus (MHV) have been used extensively for the study of viral pathogenesis in the central nervous system (CNS), serving as models for human neurological diseases such as multiple sclerosis (MS). MHV strains A59 and JHMV both cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. In acute disease, CNS damage is most likely the result of lytic infection in neurons and oligodendrocytes, and death can be prevented by the adoptive transfer of Class I‐restricted CD8+ T cells. However, in later stages of the disease induced by some MHV strains, virus tends to be restricted to astrocytes in a nonlytic infection, and the immune response appears to contribute to CNS damage. These data lead us to suggest that the astrocyte may play a central role in the neuropathogenesis of MHV infection. Consistent with this possibility, A59 has been reported to induce the expression of Class I molecules of the major histocompatibility complex (MHC) in glial cells following infection in vivo and in vitro. In this communication, we have examined the influence of persistent infection by both A59 and JHMV on MHC Class I expression in primary murine astrocytes. Persistence was characterized by the presence of intracellular viral antigen and mRNA in the absence of detectable infectious virus particles. Under these conditions, JHMV, but not A59, inhibited constitutive expression of the H‐2 K(b) molecule, with the magnitude of inhibition increasing with postinfection time. A59 was not able to induce Class I during persistence, presumably due to the lack of infectious virus particles. Class I expression was restored by the addition of gamma‐interferon (IFN‐γ) to astrocytes persistently infected with either A59 or JHMV. Thus, Class I inhibition is not a permanent consequence of JHMV persistence, and persistence does not interfere with normal signalling pathways for Class I induction. © 1995 Wiley‐Liss, Inc.


title: The biogeographical assignment of a west Kenyan rain forest remnant: further evidence from analysis of its reptile fauna

text: Aim The Kakamega Forest, western Kenya, has been biogeographically assigned to both lowland and montane forest biomes, or has even been considered to be unique. Most frequently it has been linked with the Guineo‐Congolian rain forest block. The present paper aims to test six alternative hypotheses of the zoogeographical relationships between this forest remnant and other African forests using reptiles as a model group. Reptiles are relatively slow dispersers, compared with flying organisms (Aves and Odonata) on which former hypotheses have been based, and may thus result in a more conservative biogeographical analysis. Location Kakamega Forest, Kenya, Sub‐Saharan Africa. Methods The reptile diversity of Kakamega Forest was evaluated by field surveys and data from literature resources. Faunal comparisons of Kakamega Forest with 16 other African forests were conducted by the use of the ‘coefficient of biogeographic resemblance’ using the reptile communities as zoogeographic indicators. Parsimony Analysis of Endemism and Neighbour Joining Analysis of Endemism were used to generate relationship trees based on an occurrence matrix with paup*. Results The analysis clearly supports the hypothesis that the Kakamega Forest is the easternmost fragment of the Guineo‐Congolian rain forest belt, and thus more closely related to the forests of that Central–West African complex than to any forest further east, such as the Kenyan coastal forests. Many Kenyan reptile species occur exclusively in the Kakamega Forest and its associated forest fragments. Main conclusions The Kakamega Forest is the only remnant of the Guineo‐Congolian rain forest in the general area. We assume that the low degree of resemblance identified for the Guineo‐Congolian forest and the East African coastal forest reflect the long history of isolation of the two forest types from each other. Kenyan coastal forests may have been historically connected through forest ‘bridges’ of the southern highlands with the Congo forest belt, allowing reptile species to migrate between them. The probability of a second ‘bridge’ located in the region of southern Tanzanian inselbergs is discussed. Although not particularly rich in reptile species, the area should be considered of high national priority for conservation measures.


title: Mixed viral infections of the respiratory tract; an epidemiological study during consecutive winter seasons

text: The current study aimed to describe the molecular epidemiology of mixed respiratory viral infections during consecutive winter seasons in a tertiary care hospital. Patients with symptoms of respiratory tract infection were evaluated during the 2009‐2011 and 2013‐15 winter seasons. A clinical microarray technique was used for viral detection. Clinical and epidemiological data were correlated with mixed viral detection and the need for hospitalization. In 332 out of 604 (54.4%) evaluated patients (17.6% children) a respiratory virus was identified. Mixed viral infections were diagnosed in 68/332 (20.5%) patients with virus detection (66.2% mixed Influenza‐RSV infections). Mixed viral infections were more commonly detected in children (OR 3.7; 95%CI 1.9‐5.6, P < 0.01) and patients with comorbidities. In logistic regression analyses, mixed viral infections were associated with younger age (mean age 30.4 years vs. 41.8 years, P ≤ 0.001) and increased rates of fever (OR: 2.7; 95%CI 1.04‐7.2, P < 0.05) but no adverse outcomes or increased rates of hospitalization. High rates of mixed viral infections were noted during all winter seasons (especially Influenza and RSV) and were more common in younger patients. The clinical significance of mixed respiratory viral infection needs further elucidation.


title: Pancreatic surgical biopsy in 24 dogs and 19 cats: postoperative complications and clinical relevance of histological findings

text: OBJECTIVE: To assess the immediate postoperative complications associated with pancreatic biopsy in dogs and cats and review the clinical relevance of biopsy findings. METHODS: Retrospective review of clinical records from two referral institutions for cases undergoing pancreatic biopsy between 2000 and 2013. RESULTS: Twenty‐four dogs and 19 cats that had surgical pancreatic biopsy had sufficient detail in their clinical records and fulfilled the inclusion criteria. Postoperative complications were seen in 10 cases of which 5 were suggestive of post‐surgical pancreatitis. Two patients were euthanased within 10 days of surgery because of the underlying disease; neither suffered postoperative complications. Pancreatic pathology was found in 19 cases, 7 cases showed no change other than benign pancreatic nodular hyperplasia, and no abnormalities were seen in 18 cases. CLINICAL SIGNIFICANCE: Complications may be encountered following surgical pancreatic biopsy, although the risk should be minimal with good surgical technique. Pancreatic biopsy may provide a useful contribution to case management but it is not clear whether a negative pancreatic biopsy should be used to rule out pancreatic disease. Dogs were more likely to have no significant pathology found on pancreatic biopsy than cats, where chronic pancreatitis was the most common finding.


Published Only


title: Viral infections in the acquired immunodeficiency syndrome

text: The following communication is a tripartite synopsis of the role of viral infection in the acquired immunodeficiency syndrome (AIDS). The first section describes the impact of viral opportunistic infection in AIDS; for each virus, clinical presentation and diagnosis, laboratory diagnostic approaches (with emphasis on electron microscopy), and therapeutic interventions attempted to date are discussed. The second segment explores current theories on the pathogenesis of AIDS, and describes diagnostic and therapeutic approaches to the syndrome itself. The final section catalogues ultrastructural anomalies in the cells of AIDS patients, many of which have been mistakenly identified as etiologic agents.


title: Myelin‐ and microbe‐specific antibodies in guillain‐barré syndrome

text: We surveyed the frequency of reported infections and target autoantigens in 56 Guillain Barré syndrome (GBS) patients by detecting antibodies to myelin and microbes. Sulfatide (43%), cardiolipin (48%), GD(1a) (15%), SGPG (11%), and GM(3) (11%) antibodies were the most frequently detected heterogenous autoantibodies. A wide spectrum of antimicrobial IgG and IgM antibodies were also detected; mumps‐specific IgG (66%), adenovirus‐specific IgG (52%), varicella‐zoster virus‐specific IgG (46%), and S. pneumoniae serotype 7‐specific IgG (45%) were the most prevalent. Our results indicate that polyclonal expansion of physiologic and pathologic antibodies and/or molecular mimicry likely occurs following infection and is related to other autoimmune factors in the etiology of GBS. Although no single definitive myelin‐specific autoantibody was identified, our results suggest a unique pattern of reactivity against autoantigens.


title: Rotavirus and other viruses in the stool of premature babies

text: In a 12‐month study, 363 stools of 199 premature babies nursed in a separate ward of a paediatric clinic were examined by electron microscopy and on cell culture to detect virus. Twenty‐four (6.6%) were positive for rotavirus, in one winter epidemy. From four stools Echo 22 was isolated, and in six cases virus‐like particles were detected by electron microscopy. These virus infections are not a major problem in newborns, requiring special care, as they are mostly symptomless or mild.


Editor’s Perspectives – May 2020


Development of an Efficient Bioprocess for Poultry Vaccines Using High‐density Insect Cell Culture


title: Long‐term morbidity of respiratory viral infections during chemotherapy in children with leukaemia

text: BACKGROUND: Respiratory viruses are a common cause of infection in immunosuppressed children undergoing cancer therapy. Pulmonary sequelae have been documented following respiratory viral infections (RVIs) in hematopoietic stem cell transplant (HSCT) recipients; however potential late effects in children undergoing nonmyeloablative chemotherapy have not been investigated. AIM: To evaluate the long‐term pulmonary morbidity of respiratory viral infections during chemotherapy in children with acute lymphoblastic leukemia (ALL). METHODS: Childhood ALL survivors, aged 7 to 18 years, greater than 6 months posttreatment were recruited. Exclusion criteria included HSCT or proven bacterial/fungal respiratory infection during treatment. Subjects were classified into “viral” or “control” groups according to retrospective medical records that documented the presence of laboratory‐proven RVIs during chemotherapy. Symptom questionnaires (Liverpool, ISAAC) and lung function testing (spirometry, plethysmography, diffusing capacity, forced oscillation technique to ATS/ERS standards) were then performed cross‐sectionally at the time of recruitment. RESULTS: Fifty‐four patients (31 viral, 23 control) were recruited: median (range) age 11.2 (7.2‐18.1) years, and at 4.9 (0.5‐13) years posttherapy. Abnormalities were detected in 17 (31%) individuals (8 viral, 9 control), with the most common being DLCO impairment (3 viral, 4 control) and reduced respiratory reactance at 5 Hz (5 viral, 6 control). Children with RVIs during chemotherapy reported more current respiratory symptoms, particularly wheeze (odds ratio [OR], 3.0; 95% confidence interval [CI]: 0.9‐10.0; P = .09) and cough (OR, 2.7; 95% CI: 0.8‐9.5; P = .11). No differences in lung function tests were observed between the two groups. CONCLUSIONS: Our study found children with RVIs during chemotherapy developed more long‐term respiratory symptoms than controls; however, differences did not reach statistical significance. No differences in static lung function were found between the two groups. Overall, pulmonary abnormalities and/or significant ongoing respiratory symptoms were detected in nearly a third of ALL survivors treated without HSCT. Larger, prospective studies are warranted to evaluate the etiology and clinical significance of these findings.


Conference Report


Pharyngotonsillitis


title: Flavor and odour characteristics of species of Allium in relation to their capacity to stimulate germination of sclerotia of Sclerotium cepivorum

text: Of many species or cultivars of Allium tested only six ornamental species showed little or no capacity to stimulate germination of sclerotia of Sclerotium cepivorum. All six species had S‐methyl‐L‐cysteine sulphoxide as their principal flavour and odour precursor and their overall flavour and odour levels were low. All other species and cultivars were highly stimulatory, contained considerahle amounts of S‐1 or S‐2‐propenyl‐L‐cysteine sulphoxide as flavour and odour precursors and, with a few exceptions, they possessed high overall flavour and odour levels. These included several species which are thought to be related to cultivated edible forms. With the possible exception of A. caeruleum and A. cyaneum no evidence of resistance to infection by S. cepivorum was detected.


title: Molecular profiling of oral microbiota in jawbone samples of bisphosphonate‐related osteonecrosis of the jaw

text: Oral Diseases (2012) 18, 602–612 Objective: Infection has been hypothesized as a contributing factor to bisphosphonate (BP)‐related osteonecrosis of the jaw (BRONJ). The objective of this study was to determine the bacterial colonization of jawbone and identify the bacterial phylotypes associated with BRONJ. Materials and methods: Culture‐independent 16S rRNA gene‐based molecular techniques were used to determine and compare the total bacterial diversity in bone samples collected from 12 patients with cancer (six, BRONJ with history of BP; six, controls without BRONJ, no history of BP but have infection). Results: Denaturing gradient gel electrophoresis profile and Dice coefficient displayed a statistically significant clustering of profiles, indicating different bacterial population in BRONJ subjects and control. The top three genera ranked among the BRONJ group were Streptococcus (29%), Eubacterium (9%), and Pseudoramibacter (8%), while in the control group were Parvimonas (17%), Streptococcus (15%), and Fusobacterium (15%). H&E sections of BRONJ bone revealed layers of bacteria along the surfaces and often are packed into the scalloped edges of the bone. Conclusion: This study using limited sample size indicated that the jawbone associated with BRONJ was heavily colonized by specific oral bacteria and there were apparent differences between the microbiota of BRONJ and controls.


title: Innovationen verbessern Lebensqualität von Patienten mit Hämophilie A

text: Die Hämophilie gehört zu den am längsten bekannten Erbkrankheiten. Erst in den 60er Jahren ist es jedoch gelungen, Gerinnungskonzentrate aus Blutplasma herzustellen und damit eine Behandlung einzuführen, die Patienten vor schweren Blutungen und Verkrüppelungen bewahrt.


title: Role of chronic stress and depression in periodontal diseases

text: An extensive body of experimental and clinical evidence documents the negative impact of chronic psychological stress and depression on the immune system and health. Chronic stress and depression can result in general dysregulation of the immune system, of both cellular and humoral pathways, which may contribute to pathogenic infection and concomitant periodontal tissue destruction. In general, the evidence is consistent with the hypothesis that stress can modify the host defense and progression of periodontal infections in patients susceptible to periodontitis. However, substantial evidence also indicates that these conditions can mediate risk for disease, including periodontitis, through changes in health‐related behaviors, such as oral hygiene, smoking and diet. The unequivocal interpretation of studies has also been hampered, in part, by issues related to conceptualization of stress and depression, as well as commonly associated comorbidities, such as diabetes, that can modify the onset and progression of periodontal disease. In addition, stress and depression appear to fall into a spectrum, ranging from mild to severe, involving a complex interaction of genetic background, coping strategies and environment. Differences in the conceptualization of stress and depression are probably important in assessing associations with other biologic and clinical measures. Future studies are necessary to clarify the complex interactions of chronic stress and depression in periodontal diseases.


title: Cost‐Effective Antibiotic Prescribing

text: Antibiotics are often misused, resulting in a high frequency of adverse effects, emergence of drug‐resistant organisms, and excessive costs. The high cost of antibiotics is currently receiving the greatest attention. Considerable cost savings can be achieved by appropriate prescribing of antibiotics for patients receiving these drugs prophylactically as well as for those with established infections. This article cites specific examples of how cost‐effective antibiotic prescribing practices can realize substantial cost savings without any diminished quality in patient care.


title: Zytostatika aus dem Meer

text: Bodenbakterien aus der Gruppe der Actinomyceten sind seit langem Lieferanten für hoch wirksame Antibiotika. Dagegen sind Sekundärmetaboliten aus Actinomyceten des marinen Sediments noch eher selten.


title: Plasticity for colour adaptation in vertebrates explained by the evolution of the genes pomc, pmch and pmchl

text: Different camouflages work best with some background matching colour. Our understanding of the evolution of skin colour is based mainly on the genetics of pigmentation (“background matching”), with little known about the evolution of the neuroendocrine systems that facilitate “background adaptation” through colour phenotypic plasticity. To address the latter, we studied the evolution in vertebrates of three genes, pomc, pmch and pmchl, that code for α‐MSH and two melanin‐concentrating hormones (MCH and MCHL). These hormones induce either dispersion/aggregation or the synthesis of pigments. We find that α‐MSH is highly conserved during evolution, as is its role in dispersing/synthesizing pigments. Also conserved is the three‐exon pmch gene that encodes MCH, which participates in feeding behaviours. In contrast, pmchl (known previously as pmch), is a teleost‐specific intron‐less gene. Our data indicate that in zebrafish, pmchl‐expressing neurons extend axons to the pituitary, supportive of an MCHL hormonal role, whereas zebrafish and Xenopus pmch+ neurons send axons dorsally in the brain. The evolution of these genes and acquisition of hormonal status for MCHL explain different mechanisms used by vertebrates to background‐adapt.


Use of Plant Viruses for Delivery of Vaccine Epitopes


title: Temperature Dependence of Activation Energy in Stage II Recovery in Deformed Aluminium

text: The activation energy of recovery in 99.999% aluminium deformed at 4.2 K is investigated at temperatures between 50 to 180 K by means of the change of slope method. The activation energy varies from 0.15 to 0.60 eV with raising temperature. This behaviour is simulated by considering an overlapping of several first order processes within stage II. It is supposed that the variation of activation energy in stage II is due to recovery of vacancies and their small clusters by pipe diffusion mechanism.


Poster session abstracts


Lessons learned


title: An indicator‐based problem reduction scheme for coupled reactive transport models

text: A number of effective models have been developed for simulating chemical transport in porous media; however, when a reactive chemical problem comprises multiple species within a substantial domain for a long period of time, the computational cost can become prohibitively expensive. This issue is addressed here by proposing a new numerical procedure to reduce the number of transport equations to be solved. This new problem reduction scheme (PRS) uses a predictor‐corrector approach, which “predicts” the transport of a set of non‐indicator species using results from a set of indicator species before “correcting” the non‐indicator concentrations using a mass balance error measure. The full chemical transport model is described along with experimental validation. The PRS is then presented together with an investigation, based on a 16‐species reaction‐advection‐diffusion problem, which determines the range of applicability of different orders of the PRS. The results of a further study are presented, in which a set of PRS simulations is compared with those from full model predictions. The application of the scheme to the intermediate‐sized problems considered in the present study showed reductions of up to 82% in CPU time, with good levels of accuracy maintained.


Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction 2014 Winter Meeting February 25–March 1, 2014 Doral Golf Resort & Spa Miami, Florida


title: Systematik und Biologie der Hepatitis‐Viren. Ähnliche Erkrankung – unterschiedliche Viren

text: Hepatitis‐Viren wurden und werden dadurch gefunden und letztlich auch benannt, dass man die infektiösen Agenzien – meist in Form ihrer Nukleinsäuren – im Blut von Patienten mit Leberentzündungen nachweist. Die Nomenklatur folgt dann dem Alphabet. So ist es leicht nachvollziehbar, dass durchaus sehr unterschiedliche Virustypen gefunden wurden, die strukturell keine oder nur wenig Gemeinsamkeiten aufweisen. Umso interessanter ist es, sich die Biologie der verschiedenen Hepatitis‐Viren genauer anzusehen.


title: A comparative study of sex pheromone reception in the Hadeninae (Lepidoptera: Noctuidae)

text: Abstract A comparative study of the olfactory responses to pheromone compounds was performed in twenty‐four species of Hadeninae. Electroantennograms (EAG) were recorded on male moths in response to thirty compounds and the response profiles of each species were analysed by factorial correspondence analysis. A limited number of molecules were found active and the most effective stimuli were Z9 tetradecenes and Z11 hexadecenes. The species of the Mythimna genus were most sensitive to aldehydes. Tholera decimalis did not respond to any of the molecules tested. The species belonging to the Mamestra and the Orthosia genera responded to a variety of molecules and no simple correlation was found between the genus and the EAG sensibility. Pheromone reception is discussed in relation to the taxonomy and the evolution of olfactory communication in Hadeninae.


docid: kjbktnri

title: Symposium Summaries


title: A novel glucuronosyltransferase has an unprecedented ability to catalyse continuous two‐step glucuronosylation of glycyrrhetinic acid to yield glycyrrhizin

text: Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world‐wide. However, the key UDP‐dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown. To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay. Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two‐step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site‐directed mutagenesis revealed that Gln‐352 may be important for the initial step of glucuronosylation, and His‐22, Trp‐370, Glu‐375 and Gln‐392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two‐step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products. Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin.


II. Topic Sessions


Veranstaltungskalender der DPhG


title: Peramivir for Influenza A and B Viral Infections: A Pharmacokinetic Case Series

text: OBJECTIVE: To describe the peramivir (PRV) pharmacokinetics in critically ill children treated for influenza A or B viral infections. DESIGN: Retrospective electronic medical record review of prospectively collected data from critically ill children receiving peramivir for influenza A or B viral infections in the pediatric intensive care unit (PICU). SETTING: A 189‐bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA. PATIENTS: Critically ill children admitted to the PICU who were infected with influenza between January 1, 2016 and March 31, 2018. INTERVENTIONS: None. RESULTS: Eleven patients, two females (18%) and nine males (82%), accounted for 24 peramivir samples for therapeutic drug management. The median age was 5 years (interquartile range 1.5–6.5 yrs) with a median weight of 16.4 kg (interquartile range 14–24 kg). Ten (91%) patients demonstrated a larger volume of distribution, 11 (100%) patients demonstrated an increase in clearance, and 11 (100%) patients demonstrated a shorter half‐life estimate as compared with the package insert and previous pediatric trial data for peramivir. Eight (73%) patients tested positive for a strain of influenza A and 3 (27%) patients tested positive for influenza B; 4 of 11 (36%) patients tested positive for multiple viruses. All patients had adjustments made to their dosing interval to a more frequent interval. Ten (91%) patients were adjusted to an every‐12‐hour regimen and 1 (9%) patient was adjusted to an every‐8‐hour regimen. No adverse events were associated with peramivir treatment. CONCLUSION: The pharmacokinetics of PRV demonstrated in this PICU cohort differs in comparison to healthy pediatric and adult patients, and alterations to dosing regimens may be needed in PICU patients to achieve pharmacodynamic exposures. Additional investigations in the PICU population are needed to confirm these findings.


title: Transforming growth factor‐beta 1 in humidifier disinfectant‐associated children's interstitial lung disease

text: BACKGROUND: Humidifier disinfectant‐associated children's interstitial lung disease has an unpredictable clinical course with a high morbidity and mortality. OBJECTIVES: To evaluate the differences in clinical findings between survivors and non‐survivors of humidifier disinfectant‐associated children's interstitial lung disease. To evaluate dynamic changes in serum cytokines related to inflammation and fibrosis in lung injury, and to determine whether these changes are predictive of survival in this disease. METHODS: We evaluated 17 children with humidifier disinfectant‐associated children's interstitial lung disease, from whom serum samples were obtained weekly during hospitalization. The severity of chest tomographic and lung pathologic findings was scored. Levels of several cytokines were measured in the serial serum samples. RESULTS: Seven of the 17 children were survivors. Compared to survivors, non‐survivors had greater ground‐glass attenuation on follow‐up chest tomography, higher admission neutrophil counts, and more macrophages on pathologic findings. Transforming growth factor‐beta 1 persisted at an elevated level (1,000–1,500 pg/ml) in survivors, whereas it decreased abruptly in non‐survivors. At the time of this decrease, non‐survivors had clinical worsening of their respiratory failure. Transforming growth factor‐beta 1 was positively correlated with PaO(2)/FiO(2) (r = 0.481, P < 0.0001). CONCLUSIONS: Non‐survivors exhibited more inflammatory clinical findings than survivors. Transforming growth factor‐beta 1 remained elevated in survivors, suggesting that it affected the clinical course of humidifier disinfectant‐associated children's interstitial lung disease. The prognosis of this lung disease may depend more on controlling excessive inflammation and repairing damaged lung than on fibrosis, and transforming growth factor‐beta 1 may play a key role in this process. Pediatr Pulmonol. 2016;51:173–182. © 2015 Wiley Periodicals, Inc.


SIOP ABSTRACTS


Is SARS China's Chernobyl?


title: Pediatric heart transplant from an incompletely treated influenza A‐positive donor

text: There is a shortage of pediatric donor hearts for waitlisted children, and yet nearly 50% of organs offered are not transplanted. Donor quality is often cited as a reason for declining organs offered from donors infected with influenza, presumably due to concern about disease transmission at transplant leading to severe disease. We previously described an excellent outcome after heart transplant from a donor infected with influenza B that had been treated with a complete course of oseltamivir. In this report, we describe a similar outcome after transplantation of an organ from an influenza A‐positive donor with symptomatic disease incompletely treated with oseltamivir. Due to the availability of effective antiviral treatment, we suggest that influenza A is also a manageable donor infection that need not preclude heart placement.


title: Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions

text: Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol‐induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta‐1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.


title: Disulfide conformation and design at helix N‐termini

text: To understand structural and thermodynamic features of disulfides within an α‐helix, a non‐redundant dataset comprising of 5025 polypeptide chains containing 2311 disulfides was examined. Thirty‐five examples were found of intrahelical disulfides involving a CXXC motif between the N‐Cap and third helical positions. GLY and PRO were the most common amino acids at positions 1 and 2, respectively. The N‐Cap residue for disulfide bonded CXXC motifs had average (ϕ,ψ) values of (−112 ± 25.2°, 106 ± 25.4°). To further explore conformational requirements for intrahelical disulfides, CYS pairs were introduced at positions N‐Cap‐3; 1,4; 7,10 in two helices of an Escherichia coli thioredoxin mutant lacking its active site disulfide (nSS Trx). In both helices, disulfides formed spontaneously during purification only at positions N‐Cap‐3. Mutant stabilities were characterized by chemical denaturation studies (in both oxidized and reduced states) and differential scanning calorimetry (oxidized state only). All oxidized as well as reduced mutants were destabilized relative to nSS Trx. All mutants were redox active, but showed decreased activity relative to wild‐type thioredoxin. Such engineered disulfides can be used to probe helix start sites in proteins of unknown structure and to introduce redox activity into proteins. Conversely, a protein with CYS residues at positions N‐Cap and 3 of an α‐helix is likely to have redox activity. Proteins 2010. © 2009 Wiley‐Liss, Inc.


Fragebogen zur PharmuZ “Arzneimittel gegen Tropenkrankheiten II”


title: Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds

text: The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components. Copyright © 2008 John Wiley & Sons, Ltd.


Meeting Report


title: A Review of the Magnetic Relaxation and Its Application to the Study of Atomic Defects in α‐Iron and Its Diluted Alloys

text: This review presents a comprehensive survey on intensive studies performed during the last decades on point defect reactions on α‐iron (α‐Fe) and its diluted alloys. Our intention is to give an actual account of the knowledge accumulated on this subject, as it has been obtained predominantly by means of the magnetic after‐effect (MAE) spectroscopy. After a concise introduction into the theoretical and experimental fundamentals of this technique, the main concern is focused on the presentation and detailed discussion of the MAE spectra arising — after low‐temperature electron (e(–))‐ or neutron(n)‐irradiation and subsequent annealing — in: (i) high‐purity α‐Fe and α‐Fe doped with (ii) substitutional solutes (like Ni, V, Al, Cu, Ti, Be, Si, Mn, …) or (iii) interstitial solutes (like O, H, C, N). During the course of systematic annealing treatments, these respective spectra undergo dramatic variations at specific temperatures thereby revealing in great detail the underlying intrinsic reactions of the radiation‐induced defects, i.e., reorientation, migration, clustering, dissolution and finally annihilation. In alloyed Fe systems the corresponding reaction sequences are even multiplied due to additional interactions between defects and solute atoms. Most valuable information concerning formation‐, dissociation‐ and binding enthalpies of small, mixed clusters (of the type C(i)V(k), N(i)V(k); i, k ≥ 1) has been obtained in high‐purity α‐Fe base material which, after charging with C or N, had been e(–)‐irradiated. Concerning the basic recovery mechanisms in α‐Fe, two complementary results are obtained from the analysis of the various systems: (i) in high‐purity and substitutionally alloyed α‐Fe the recovery in Stage‐III (200 K) is governed by a three‐dimensionally migrating (H (M) (I) = 0.56 eV) stable interstitial (dumb‐bell); (ii) following the formation and dissociation kinetics of small clusters (C(1)V(k), N(1)V(k)) in interstitially alloyed α‐Fe the migration enthalpy of the monovacancy must hold the following relation H (M) (N) (0.76 eV) < H (M) (C) (0.84 eV) < H (M) (V1). These results are in clear agreement with the so‐called two‐interstitial model (2IM) in α‐Fe – a conclusion being further substantiated by a systematic comparison with the results obtained from nonrelaxational techniques, like i.e. positron annihilation (PA), which by their authors are preferentially interpreted in terms of the one‐interstitial model (1IM).


Scientific Content P1–P85


title: Factors Influencing the Size Structure of Brook Trout and Brown Trout in Southeastern Wyoming Mountain Streams

text: We used discriminant models to identify relations among size structures of stocks of brook trout Salvelinus fontinalis and brown trout Salmo trutta and features of their habitats in small mountain streams (2,377–2,975 m above mean sea level) in the Medicine Bow National Forest, Wyoming. Size structure was predicted from position of the study reach in the watershed, from channel gradient, and from composition of the salmonid community. Brook trout were predominantly small in high‐elevation, moderate‐gradient, forested reaches with allopatric populations; they were larger in mid‐elevation, low‐gradient, meadow reaches that contained some brown trout. Brown trout were mostly small in mid‐elevation, moderate‐gradient, forested reaches; however, more large brown trout occurred lower in the watersheds, in meadow or rangeland stream reaches that had low gradients and that supported allopatric populations.


docid: foymxwoe

title: 2016 ASPHO ABSTRACTS


title: Multi‐season analyses of causative pathogens in children hospitalized with asthma exacerbation

text: BACKGROUND: Respiratory viral and mycoplasma infections are associated with childhood asthma exacerbations. Here, we explored epidemiologic profile of causative pathogens and possible factors for exacerbation in a single center over a three‐year period. METHODS: Hospitalized asthmatic children with attack aged 6 months‐17 years were recruited between 2012 and 2015 (n = 216). Nasopharyngeal mucosa cell samples were collected from the participants and examined by reverse transcription‐polymerase chain reaction to detect rhinovirus (RV), respiratory syncytial virus (RSV), enterovirus (EV), parainfluenza virus (PIV), Mycoplasma pneumoniae, and others. Clinical features, laboratory data, asthma exacerbation intensity, and asthma severity were compared among participants. Epidemiologic profile of causative pathogens and possible factors for exacerbation were explored. RESULTS: Viruses and/or Mycoplasma pneumoniae were detected in 75% of the participants. Rhinovirus (48%) was the most commonly detected virus in the participants with single infection, followed by RSV (6%). The median age at admission in the RV group was significantly higher than that in the RSV group. Insufficient asthma control and allergen sensitization were significantly related to RV‐associated asthma exacerbation. There was no seasonality of pathogen types associated with asthma exacerbation although a sporadic prevalence of EV‐D68 was observehinovirud. Rhinovirus were repeatedly detected in multiple admission cases. CONCLUSION: Our three‐year analysis revealed that patients with RV infection were significantly prone to repeated RV infection in the subsequent exacerbation and good asthma control could prevent RV‐associated asthma development and exacerbation. Multiple‐year monitoring allowed us to comprehend the profile of virus‐ and/or mycoplasma‐induced asthma exacerbation.


title: THE FINE STRUCTURE OF THE CNS IN MULTIPLE SCLEROSIS. I. INTERPRETATION OF CYTOPLASMIC PAPOVAVIRUS‐LIKE AND PARAMYXOVIRUS‐LIKE INCLUSIONS

text: During an electron microscopic study of the white matter in multiple sclerosis (MS), spheroidal reticular particles were found both in MS and in control brains. These particles have previously been described in the brain in MS and in brain‐derived cell cultures in subacute sclerosing panencephalitis. In both cases they were interpreted as papovaviruses, but in size, morphology and distribution they are identical to the reticulosomes and related particles which occur as proteinaceous artefacts in a variety of tissues and in subcellular fractions. Inclusions in endothelial cell cytoplasm, previously reported from the CNS in MS as paramyxovirus similar to measles, have also been found in the present study. They were present both in MS and in control brains and are identified as ‘rod‐shaped tubular bodies’, normally occurring organelles of endothelial cells. The necessity for a cautious interpretation of virus‐like inclusions is emphasized.


2018 ASPHO ABSTRACTS


title: Urinary club cell protein 16 (CC16): Utility of its assay during acute bronchiolitis

text: Acute bronchiolitis is responsible for high morbidity in infants. Club cell protein 16 kDa (CC16) is a major pneumoprotein secreted by club cells of the bronchial epithelium and eliminated by the renal pathway. CC16 seems to be a biomarker of epithelial damage in asthma. However, its value as a marker of acute bronchiolitis severity and later recurrent wheezing are uncertain, especially the value of its urinary assay for this purpose. A prospective, observational, analytical study was conducted at Clermont‐Ferrand University Hospital to correlate serum CC16 level with clinical severity of bronchiolitis in hospitalized infants aged less than 1 year. We analyzed correlations between serum and urinary CC16, CC16 levels and Wainwright score, immediate morbidity due to bronchiolitis, causal viruses, and recurrent wheezing 1 year after inclusion. In 166 infants, serum CC16 did not correlate with acute bronchiolitis severity (P = .49), but urinary CC16 did (P < .001). In multivariate analysis, urinary CC16 correlated mainly with urinary retinol binding protein (RBP; r = 0.70; P < .001). The logCC16u/logRBPu ratio correlated significantly with severity (P = .02). CC16 levels were not correlated with recurrent wheezing at 1 year. Urinary CC16 could be a useful biomarker in acute bronchiolitis for specific indications. This noninvasive assay would be particularly useful in the young infant population. Several factors must be taken into account in its interpretation, mainly tubular function. Further studies are needed to assess these factors.


title: Lipid transfer proteins from Brassica campestris and mung bean surpass mung bean chitinase in exploitability

text: Antifungal peptides with a molecular mass of 9 kDa and an N‐terminal sequence demonstrating remarkable similarity to those of nonspecific lipid transfer proteins (nsLTPs) were isolated from seeds of the vegetable Brassica campestris and the mung bean. The purified peptides exerted an inhibitory action on mycelial growth in various fungal species. The antifungal activity of Brassica and mung bean nsLTPs were thermostable, pH‐stable, and stable after treatment with pepsin and trypsin. In contrast, the antifungal activity of mung bean chitinase was much less stable to changes in pH and temperature. Brassica LTP inhibited proliferation of hepatoma Hep G2 cells and breast cancer MCF 7 cells with an IC(50) of 5.8 and 1.6 µm, respectively, and the activity of HIV‐1 reverse transcriptase with an IC(50) of 4 µm. However, mung bean LTP and chitinase were devoid of antiproliferative and HIV‐1 reverse transcriptase inhibitory activities. In contrast to the mung bean LTP, which exhibited antibacterial activity, Brassica LTP was inactive. All three antifungal peptides lacked mitogenic activity toward splenocytes. These results indicate that the two LTPs have more desirable activities than the chitinase and that there is a dissociation between the antifungal and other activities of these antifungal proteins. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.


title: Anti‐HIV, Anti‐Poxvirus, and Anti‐SARS Activity of a Nontoxic, Acidic Plant Extract from the Trifollium Species Secomet‐V/anti‐Vac Suggests That It Contains a Novel Broad‐Spectrum Antiviral

text: Enveloped animal viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, human papillomavirus, Marburg, and influenza are major public health concerns around the world. The prohibitive cost of antiretroviral (ARV) drugs for most HIV‐infected patients in sub‐Saharan Africa and the serious side effects in those who have access to ARV drugs make a compelling case for the study of complementary and alternative therapies. Such therapies should have scientifically proved antiviral activity and minimal toxic effects. A plant extract, Secomet‐V, with an anecdotal indication in humans for promise as an anti‐HIV treatment, was investigated. Using a previously described attenuated vaccinia virus vGK5, we established the antiviral activity of Secomet‐V. Chemical analysis showed that it has an acidic pH, nontoxic traces of iron (<10 ppm), and almost undetectable levels of arsenic (<1.0 ppm). The color varies from colorless to pale yellow to dark brown. The active agent is heat stable at least up to sterilizing temperature of 121°C. The crude plant extract is a mixture of several small molecules separable by high‐pressure liquid chromatography. The HIV viral loads were significantly reduced over several months in a few patients monitored after treatment with Secomet‐V. Secomet‐V was also found to have antiviral activity against the SARS virus but not against the West Nile virus. Secomet‐V, therefore, is a broad‐spectrum antiviral, which possibly works by neutralizing viral infectivity, resulting in the prevention of viral attachment.


Mechanisms of Virus‐Induced Demyelination and Remyelination


Specific RNA Drug Therapy of Hepatitis Viruses


title: Mold contamination in schools with either high or low prevelance of asthma

text: BACKGROUND: Mold exposures have been linked to the development and exacerbation of asthma. The purpose of this study was to determine whether the Environmental Relative Moldiness Index (ERMI) metric, developed to quantify mold exposures in homes, might be applied to evaluating the mold contamination in schools. METHODS: Settled dust samples (n = 10) were collected on each level of a water‐damaged school in Springfield, Massachusetts and two samples per level in five Idaho schools. Each dust sample was analyzed for the 36 molds that make up the ERMI. The concentration of 2.5‐μm particulate matter (PM (2.5)) was measured in each school at two locations during the spring of 2013. RESULTS: The average ERMI value in the Springfield school, 15.51, was significantly greater (p < 0.001) than the average ERMI value, −2.87, in the Idaho schools. Ten of the twenty‐six Group 1 molds, which are associated with water‐damaged environments, were in significantly greater concentrations in the Springfield school. The populations of Group 2 molds, which are common indoors even without water damage, were essentially the same in Springfield and Idaho schools. The average PM (2.5) concentration in the Springfield and Idaho schools was 11.6 and 3.4 μg/m(3), respectively. CONCLUSIONS: The ERMI scale might be useful in comparing the relative mold contamination in schools.


COMPARISON OF THE DEVELOPMENT OF RESISTANT STRAINS OF TYPE 1 HERPES SIMPLEX VIRUS TO IN VITRO ANTIVIRAL ACTIVITY OF 5‐IODO‐2‐ DEOXYURIDINE OR RIBAVIRIN.


title: Label‐free detection techniques for protein microarrays: Prospects, merits and challenges

text: Protein microarrays, on which thousands of discrete proteins are printed, provide a valuable platform for functional analysis of the proteome. They have been widely used for biomarker discovery and to study protein–protein interactions. The accomplishments of DNA microarray technology, which had enabled massive parallel studies of gene expression, sparked great interest for the development of protein microarrays to achieve similar success at the protein level. Protein microarray detection techniques are often classified as being label‐based and label‐free. Most of the microarray applications have employed labelled detection such as fluorescent, chemiluminescent and radioactive labelling. These labelling strategies have synthetic challenges, multiple label issues and may exhibit interference with the binding site. Therefore, development of sensitive, reliable, high‐throughput, label‐free detection techniques are now attracting significant attention. Label‐free detection techniques monitor biomolecular interactions and simplify the bioassays by eliminating the need for secondary reactants. Moreover, they provide quantitative information for the binding kinetics. In this article, we will review several label‐free techniques, which offer promising applications for the protein microarrays, and discuss their prospects, merits and challenges.


Influence of viral and bacterial respiratory infections on exacerbations and symptom severity in childhood asthma


title: Hochkontagiöse Erkrankungen. Sind wir vorbereitet?

text: Hochkontagiöse, gemeingefährliche, lebensbedrohliche Erkrankungen kommen in Deutschland bislang extrem selten vor, bergen aber ein hohes Gefahrenpotential für Patienten, Gesundheitspersonal und die allgemeine Bevölkerung. Sie können als importierte Infektionen, bei Laborunfällen oder im Rahmen bioterroristischer Anschläge vorkommen. Besondere Bedeutung haben die Mensch zu Mensch übertragbaren viralen hämorrhagischen Fieber (vor allem Ebola, Marburg, Lassa, Krim‐Kongo hämorrhagisches Fieber), Pockenerkrankungen und die Lungenpest. Anamnese und klinisches Bild erlauben Fachleuten, einen “begründeten Verdacht” auszusprechen, was eine Reihe spezifischer Maßnahmen nach sich ziehen muss. Diese sollten in Alarmplänen vorbereitet sein, deren Umsetzung ein enges Zusammenspiel zwischen Klinikern, Öffentlichem Gesundheitsdienst und Experten voraussetzt. Deutschland ist durch das Netzwerk der StAKoB im internationalen Vergleich sehr gut aufgestellt.


Arzt und Apotheker – vertrauensvolle Partner oder feindliche Brüder?


title: Poly(N‐acylethylenimine) copolymers containing pendant pentamethyldisiloxanyl groups. I. Synthesis

text: 10‐(Pentamethyl disiloxanyl) decyl oxazoline (Si) was synthesized. It was copolymerized with either undecyl (U) or nonyl (N) oxazolines using methyl 4‐nitrobenzenesulfonate as initiator. Two series of random poly(N‐acylethylenimine) copolymers, U/Si and N/Si, were synthesized over the whole composition range of Si monomer with a total degree of polymerization of about 100. Narrow molecular weight distributions were obtained. At a monomer to initator ratio of about 1060, the final degree of polymerization was 374 with a polydispersity index of 1.93. This shows the effect of chain transfer in this system.


title: Quantitative proteomic analysis of A549 cells infected with human respiratory syncytial virus subgroup B using SILAC coupled to LC‐MS/MS

text: Human respiratory syncytial virus (HRSV) is a leading cause of serious lower respiratory tract infections in infants. The virus has two subgroups A and B, which differ in prevalence and (nucleotide) sequence. The interaction of subgroup A viruses with the host cell is relatively well characterized, whereas for subgroup B viruses it is not. Therefore quantitative proteomics was used to investigate the interaction of subgroup B viruses with A549 cells, a respiratory cell line. Changes in the cellular proteome and potential canonical pathways were determined using SILAC coupled to LC‐MS/MS and Ingenuity Pathway Analysis. To reduce sample complexity and investigate potential trafficking both nuclear and cytoplasmic fractions were analyzed. A total of 904 cellular and six viral proteins were identified and quantified, of which 112 cellular proteins showed a twofold or more change in HRSV‐infected cells. Data sets were validated using indirect immunofluorescence confocal microscopy on independent samples. Major changes were observed in constituents of mitochondria including components of the electron transport chain complexes and channels, as well as increases in the abundance of the products of interferon‐stimulated genes. This is the first quantitative proteomic analysis of cells infected with HRSV‐subgroup B.


title: High incidence of ubiquitin‐like domains in human ubiquitin‐specific proteases

text: Ubiquitin‐specific proteases (USPs) emerge as key regulators of numerous cellular processes and account for the bulk of human deubiquitinating enzymes (DUBs). Their modular structure, mostly annotated by sequence homology, is believed to determine substrate recognition and subcellular localization. Currently, a large proportion of known human USP sequences are not annotated either structurally or functionally, including regions both within and flanking their catalytic cores. To extend the current understanding of human USPs, we applied consensus fold recognition to the unannotated content of the human USP family. The most interesting discovery was the marked presence of reliably predicted ubiquitin‐like (UBL) domains in this family of enzymes. The UBL domain thus appears to be the most frequently occurring domain in the human USP family, after the characteristic catalytic domain. The presence of multiple UBL domains per USP protein, as well as of UBL domains embedded in the USP catalytic core, add to the structural complexity currently recognized for many DUBs. Possible functional roles of the newly uncovered UBL domains of human USPs, including proteasome binding, and substrate and protein target specificities, are discussed. Proteins 2007. © 2007 Wiley‐Liss, Inc.


title: Optimizing Economic Outcomes in Acute Exacerbations of Chronic Bronchitis

text: The treatment of community‐acquired respiratory tract infections, such as acute exacerbations of chronic bronchitis (AECB), constitutes a huge socioeconomic burden. In most cases, an antimicrobial agent is advocated to lessen morbidity and prevent serious clinical sequelae. Use of antimicrobial agents for AECB, however, is controversial, as it is difficult to distinguish between bacterial and nonbacterial AECB, and only marginal benefits have been reported. Antimicrobial agents, however, have reduced relapse rates, prolonged the time between exacerbations, shortened the duration of symptoms, and reduced the need for hospitalization. Microbiologic resistance and individual patient characteristics play important roles in determining the most appropriate antimicrobial agent for patients with AECB. More research on the effect of resistant bacteria on antimicrobial response rates will enable physicians to prescribe economically rational antimicrobial therapy for this common infection.


Measles Virus Infection Causes Expression of Class I and Class II MHC Antigens in Rat Brain


EFFECT OF RIBAVIRIN ON VIRAL HEPATITIS IN LABORATORY ANIMALS


Transfection of COS Cells with Human Cystatin cDNA and Its Effect on HSV‐1 Replication


title: CAN VIRAL ENVELOPE GLYCOLIPIDS PRODUCE AUTO‐IMMUNITY, WITH REFERENCE TO THE CNS AND MULTIPLE SCLEROSIS?

text: Many viruses, with lipid envelopes derived from the host cell membranes, have been implicated in the aetiology of multiple sclerosis (MS), and epidemiological studies support an infectious agent. Alternatively the disease is thought by other workers to be auto‐immune in nature, and recently much attention has been focused on immunological sensitivity to glycolipids in MS patients. In this paper it is proposed that CNS demyelination could arise in susceptible individuals (HLA type) from an immune response to glycolipids, triggered by the carrier effect of one or more enveloped neurotropic viruses.


Cell‐Mediated Immunity in Virus Infections of the Central Nervous System


title: New insights into pediatric community‐acquired pneumonia gained from untargeted metabolomics: A preliminary study

text: BACKGROUND: Available diagnostics often fail to distinguish viral from bacterial causes of pediatric community‐acquired pneumonia (pCAP). Metabolomics, which aims at characterizing diseases based on their metabolic signatures, has been applied to expand pathophysiological understanding of many diseases. In this exploratory study, we used the untargeted metabolomic analysis to shed new light on the etiology of pCAP. METHODS: Liquid chromatography coupled with mass spectrometry was used to quantify the metabolite content of urine samples collected from children hospitalized for CAP of pneumococcal or viral etiology, ascertained using a conservative algorithm combining microbiological and biochemical data. RESULTS: Fifty‐nine children with CAP were enrolled over 16 months. Pneumococcal and viral cases were distinguished by means of a multivariate model based on 93 metabolites, 20 of which were identified and considered as putative biomarkers. Among these, six metabolites belonged to the adrenal steroid synthesis and degradation pathway. CONCLUSIONS: This preliminary study suggests that viral and pneumococcal pneumonia differently affect the systemic metabolome, with a stronger disruption of the adrenal steroid pathway in pneumococcal pneumonia. This finding may lead to the discovery of novel diagnostic biomarkers and bring us closer to personalized therapy for pCAP.


title: Konzepte für die Hämophilie‐Behandlung. Gerinnungsfaktoren in der Therapie

text: Angeborene Blutungsleiden sind überwiegend durch genetische Defekte der im Blutplasma vorkommenden Gerinnungsfaktoren (I‐XIII) bedingt (Koagulopathien). Ursächlich kommen auch angeborene Störungen der Thrombozytenfunktion und extrem selten solche der Gefäßwand infrage.


docid: yskxbzer

title: Is an infectious trigger always required for primary hemophagocytic lymphohistiocytosis? Lessons from in utero and neonatal disease

text: In this report, we evaluate the hypothesis that hemophagocytic lymphohistiocytosis in patients with defects of lymphocyte cytotoxicity is usually triggered by infections. We show that in the majority of patients, extensive virus PCR panels performed in addition to routine microbiological investigations remain negative and summarize 25 patients with onset of hemophagocytic lymphohistiocytosis in utero or within the first 10 days of life, in none of which an associated bacterial or viral infection was reported. These observations, even though preliminary, invite to consider a key role of lymphocyte cytotoxicity in controlling T‐cell homeostasis also in the absence of apparent infectious stimuli.


title: Tight junction‐related human diseases

text: Tight junctions are intercellular junctions adjacent to the apical ends of paracellular spaces. They have two classical functions, the barrier function and the fence function. The former regulates the passage of ions, water and various molecules through paracellular spaces, and is thus related to edema, jaundice, diarrhea and blood‐borne metastasis. The latter function maintains cell polarity by forming a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell properties in terms of loss of cell polarity. Recently, two novel aspects of tight junctions have been reported. One is their involvement in signal transduction. The other is that fact that tight junctions are considered to be a crucial component of innate immunity. In addition, since some proteins comprising tight junctions work as receptors for viruses and extracellular stimuli, pathogenic bacteria and viruses target and affect the tight junction functions, leading to diseases. In this review, the relationship between tight junctions and human diseases will be described.


Negative Staining and Immune Electron Microscopy as Techniques for Rapid Diagnosis of Viral Agents


title: Severe, persistent, and fatal T‐cell immunodeficiency following therapy for infantile leukemia

text: We describe five cases of children who completed chemotherapy for infantile acute lymphoblastic leukemia (ALL) and soon after were diagnosed with severe T‐cell, non‐HIV immunodeficiency, with varying B‐cell and NK‐cell depletion. There was near absence of CD3(+), CD4(+), and CD8(+) cells. All patients developed multiple, primarily opportunistic infections. Unfortunately, four patients died, although one was successfully treated by hematopoietic stem cell transplantation. These immunodeficiencies appeared to be secondary to intensive infant ALL chemotherapy. Our report highlights the importance of the early consideration of this life‐threatening immune complication in patients who received chemotherapy for infantile ALL.


title: Microsensor Arrays for Saliva Diagnostics

text: abstract: Optical fiber microarrays have been used to screen saliva from patients with end‐stage renal disease (ESRD) to ascertain the efficacy of dialysis. We have successfully identified markers in saliva that correlate with kidney disease. Standard assay chemistries for these markers have been converted to disposable test strips such that patients may one day be able to monitor their clinical status at home. Details of these developments are described. In addition, saliva from asthma and chronic obstructive pulmonary disease (COPD) patients is being screened for useful diagnostic markers. Our goal is to develop a multiplexed assay for these protein and nucleic acid biomarkers for diagnosing the cause and severity of pulmonary exacerbations, enabling more effective treatment to be administered. These results are reported in the second part of this article.


title: Trends in der Impfstoffentwicklung. DNA‐ und zellbasierte Impfstoffe

text: Für eine Reihe von Infektionskrankheiten sowohl bakterieller, parasitärer als auch viraler Genese wurde vor allem im 20. Jahrhundert eine Vielzahl von Impfstoffen entwickelt, die Impflinge erfolgreich schützen konnten. Dies führte zu einer drastisch verminderten Krankheitslast in der Bevölkerung, zu einer deutlich verringerten Säuglingssterblichkeit und zu einer Erhöhung der Lebenserwartung. Aktuell werden die globalen Bemühungen intensiviert, das Poliomyelitis‐ und das Masern‐Virus auszurotten.


Academy News – April 2020 PM&R


Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland


46(th) Congress of the International Society of Paediatric Oncology (SIOP) 2014: Toronto, Canada 22(nd)–25(th) October, 2014 SIOP abstracts


title: Neither insects nor wind: ambophily in dioecious Chamaedorea palms (Arecaceae)

text: Pollination of Neotropical dioecious trees is commonly related to generalist insects. Similar data for non‐tree species with separated genders are inconclusive. Recent studies on pollination of dioecious Chamaedorea palms (Arecaceae) suggest that species are either insect‐ or wind‐pollinated. However, the wide variety of inflorescence and floral attributes within the genus suggests mixed pollination mode involving entomophily and anemophily. To evaluate this hypothesis, we studied the pollination of Chamaedorea costaricana,C. macrospadix,C. pinnatifrons and C. tepejilote in two montane forests in Costa Rica. A complementary morphological analysis of floral traits was carried out to distinguish species groups within the genus according to their most probable pollination mechanism. We conducted pollinator exclusion experiments, field observations on visitors to pistillate and staminate inflorescences, and trapped airborne pollen. A cluster analysis using 18 floral traits selected for their association with wind and insect pollination syndromes was carried out using 52 Chamaedorea species. Exclusion experiments showed that both wind and insects, mostly thrips (Thysanoptera), pollinated the studied species. Thrips used staminate inflorescences as brood sites and pollinated pistillate flowers by deception. Insects caught on pistillate inflorescences transported pollen, while traps proved that pollen is wind‐borne. Our empirical findings clearly suggest that pollination of dioecious Chamaedorea palms is likely to involve both insects and wind. A cluster analysis showed that the majority of studied species have a combination of floral traits that allow for both pollination modes. Our pollination experiments and morphological analysis both suggest that while some species may be completely entomophilous or anemophilous, ambophily might be a common condition within Chamaedorea. Our results propose a higher diversity of pollination mechanisms of Neotropical dioecious species than previously suggested.


title: Characterization of Bovine Parainfluenza Virus Type 3

text: Bovine parainfluenza virus type 3 (PIV‐3) has a buoyant density of 1.197. The RNA of PIV‐3, like that of Sendai virus, is a single continuous chain which lacks polyadenylic acid sequences and tends to self‐anneal to a marked extent. It has a sedimentation coefficient of 42S and a molecular weight of 4.5 × 10(6), being slightly smaller than Sendai virus RNA (47S, 5.3 × 10(6)). PIV‐3 has 5 main structural proteins, of which 2 are glycoproteins. The molecular weights of protein(1), protein(2), protein(3), glycoprotein(1), and glycoprotein(2) were estimated to be 79,000, 68,000, 35,000, 69,000, and 55,000, respectively. Protein(2) was suggested to be nucleocapsid protein.


title: Comparison of Three Electron Microscopy Techniques for the Detection of Human Rotaviruses

text: Rotavirus detection by direct electron microscopy was compared with direct and indirect immune electron microscopy techniques. The latter two approaches permitted the enumeration of 25 and 103 times more rotaviruses respectively, than direct electron microscopy. Also, 70% and 90% of the virus particles were aggregated by direct and indirect immune electron microscopy techniques respectively, thus facilitating their detection.


title: Characterization of Small Plaque Mutants of Mouse Hepatitis Virus, JHM Strain

text: Two small plaque mutants designated as 1a and 2c were isolated from DBT cells persistently infected with the JHM strain of mouse hepatitis virus. Unlike the wild type JHM, these two mutant viruses grew more slowly with no prominent cell fusion. The buoyant densities of the mutants were slightly lower and 2c was revealed to have fewer peplomers than JHM by electron microscopy. The purified JHM contained five polypeptides with molecular weights (M.W.) of 260,000, 105,000 (GP105), 65,000, 60,000 (P60), and 23,000 (GP23). In addition to two polypeptides, P60 and GP23, which were common to JHM and the mutants, 1a was found to contain three other specific polypeptides with M.W. of 180,000 (GP160), 110,000, and 95,000 (GP95), while 2c had GP180, GP105, GP95, and one with a M.W. of 175,000. All of these polypeptides were shown to be glycosylated except for P60. After bromelain treatment, all these viruses lost the peplomers and contained P60 and another new 18,000 dalton polypeptide.


title: Flavivirus induces MHC antigen on human myoblasts: A model of autoimmune myositis?

text: Infection of human embryonic myoblasts by West Nile virus (WNV), a flavivirus, caused significant upregulation of class I and II MHC expression as determined by flow cytometry. After 48 hours at a multiplicity of infection of 5 pfu/cell, a sixfold increase in MHC class I expression was induced from initially low levels of expression. In contrast, MHC class II was induced de novo to five times the control fluorescence level. At least 70% of the cells were infected as determined using fluorescence microscopy and anti‐WNV antibody labeling. Myoblasts were > 90% pure as shown by anti–Leu‐19 labeling. MHC class I (but not class II) was increased threefold after exposure to virus‐inactivated supernatant from 48‐hour–infected cells, indicating the presence of factor(s) contributing to the MHC class I increase. These findings may be important in establishing a link between viral infection of human cells and induction of inflammatory autoimmune disease. We discuss the possibility of using WNV as an in vivo model. © 1992 John Wiley & Sons, Inc.


Tea and Health – Interview with Yukihiko Hara, Mitsui Norin Co., Ltd.


docid: asjxwlrn

title: Retracted: Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue

text: Retraction statement: ‘Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue’ by Yan Liu, Junmei Zhou, Zhizhun Yu, Danyun Fang, Chunyun Fu, Xun Zhu, Zhenjian He, Huijun Yan, Wenquan Liu, Yunxia Tang, Mengfeng Li and Lifang Jiang. The above article in Microbiology and Immunology (doi: 10.1111/1348‐0421.12179), published online on 15 July 2014 in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the authors, the journal Editors‐in‐Chief, Akio Nakane, Takaji Wakita, Yasunobu Yoshikai, and Wiley Publishing Asia Pty Ltd. The retraction has been agreed as the article was submitted by Dr. Liu Y. without agreement of all co‐authors, including two listed corresponding authors.


title: Treatment of idiopathic spasmodic torticollis with botulinum‐A toxin: a pilot study of 19 patients

text: Nineteen patients with spasmodic torticollis, unresponsive to standard therapy, were administered local injections of botulinum‐A toxin into the affected muscles. During an average follow‐up period of 11.5 months, a more than 25% improvement was noted in 14 of 19 patients. All those with purely focal dystonia and 9 of 10 patients with a disease history of less than three years benefited from treatment. Side effects were insignificant and transient. Botulinum toxin is a very effective and safe method of treatment for spasmodic torticollis.


title: Canine distemper virus in the Serengeti ecosystem: molecular adaptation to different carnivore species

text: Was the 1993/1994 fatal canine distemper virus (CDV) epidemic in lions and spotted hyaenas in the Serengeti ecosystem caused by the recent spillover of a virulent domestic dog strain or one well adapted to these noncanids? We examine this question using sequence data from 13 ‘Serengeti’ strains including five complete genomes obtained between 1993 and 2011. Phylogenetic and haplotype network analyses reveal that strains from noncanids during the epidemic were more closely related to each other than to those from domestic or wild canids. All noncanid ‘Serengeti’ strains during the epidemic encoded: (1) one novel substitution G134S in the CDV‐V protein; and (2) the rare amino acid combination 519I/549H at two sites under positive selection in the region of the CDV‐H protein that binds to SLAM (CD 150) host cell receptors. Worldwide, only a few noncanid strains in the America II lineage encode CDV‐H 519I/549H. All canid ‘Serengeti’ strains during the epidemic coded CDV‐V 134G, and CDV‐H 519R/549Y, or 519R/549H. A functional assay of cell entry revealed the highest performance by CDV‐H proteins encoding 519I/549H in cells expressing lion SLAM receptors, and the highest performance by proteins encoding 519R/549Y, typical of dog strains worldwide, in cells expressing dog SLAM receptors. Our findings are consistent with an epidemic in lions and hyaenas caused by CDV variants better adapted to noncanids than canids, but not with the recent spillover of a dog strain. Our study reveals a greater complexity of CDV molecular epidemiology in multihost environments than previously thought.


title: A high frequency of allopolyploid speciation in the gymnospermous genus Ephedra and its possible association with some biological and ecological features

text: The origin and evolution of polyploids have been studied extensively in angiosperms and ferns but very rarely in gymnosperms. With the exception of three species of conifers, all natural polyploid species of gymnosperms belong to Ephedra, in which more than half of the species show polyploid cytotypes. Here, we investigated the origin and evolution of polyploids of Ephedra distributed in the Qinghai–Tibetan Plateau (QTP) and neighbouring areas. Flow cytometry (FCM) was used to measure the ploidy levels of the sampled species that are represented by multiple individuals from different populations, and then, two single‐copy nuclear genes (LFY and DDB2) and two chloroplast DNA fragments were used to unravel the possible origins and maternal donors of the polyploids. The results indicate that the studied polyploid species are allopolyploids, and suggest that allotetraploidy is a dominant mode of speciation in Ephedra. The high percentage of polyploids in the genus could be related to some of its biological attributes such as vegetative propagation, a relatively high rate of unreduced gamete formation, and a small genome size relative to most other gymnosperms. Significant ecological divergences between allotetraploids and their putative progenitors were detected by PCAs and anova and Tukey's tests, with the exception of E. saxatilis. The overlap of geographical distributions and ecological niches of some diploid species could have provided opportunities for interspecific hybridization and allopolyploid speciation.


title: Distribution of split DnaE inteins in cyanobacteria

text: Inteins are genetic elements found inside the coding regions of different host proteins and are translated in frame with them. The intein‐encoded protein region is removed by an autocatalytic protein‐splicing reaction that ligates the host protein flanks with a peptide bond. This reaction can also occur in trans with the intein and host protein split in two. After translation of the two genes, the two intein parts ligate their flanking protein parts to each other, producing the mature protein. Naturally split inteins are only known in the DNA polymerase III alpha subunit (polC or dnaE gene) of a few cyanobacteria. Analysing the phylogenetic distribution and probable genetic propagation mode of these split inteins, we conclude that they are genetically fixed in several large cyanobacterial lineages. To test our hypothesis, we sequenced parts of the dnaE genes from five diverse cyanobacteria and found all species to have the same type of split intein. Our results suggest the occurrence of a genetic rearrangement in the ancestor of a large division of cyanobacteria. This event fixed the dnaE gene in a unique two‐genes one‐protein configuration in the progenitor of many cyanobacteria. Our hypothesis, findings and the cloning procedure that we established allow the identification and acquisition of many naturally split inteins. Having a large and diverse repertoire of these unique inteins will enable studies of their distinct activity and enhance their use in biotechnology.


title: Could preventive intranasal interferon lower the morbidity in children prone to respiratory illness?

text: Recent studies have demonstrated that rhinovirus infections can be prevented in the family setting through use of intranasal interferon sprays which are commenced when another family member develops a cold. One hundred and twenty‐seven children aged 4–9 years who had been hospitalized during their first year of life for severe infections caused by respiratory syncytial virus were studied virologically and epidemiologically during a seven‐month period which included the winter months. The hypothesis was that a significant part of their respiratory morbidity would be preventable by a contact prophylaxis approach using intranasal interferon. However, the findings suggest that a preventive approach of this kind would not substantially reduce the burden of respiratory illness in these children because: the target children themselves more often introduced illness into the family than did other household members; rhinovirus infections preventable by interferon were associated with little lower respiratory morbidity; and rhinoviruses were minor contributors to the total respiratory illness burden in these respiratory illness‐prone children.


title: Use of Protein A in the Serum‐in‐Agar Diffusion Method in Immune Electron Microscopy for Detection of Virus Particles in Cell Culture

text: A modified technique using protein A in the serum‐in‐agar (SIA) method for immune electron microscopy (IEM) was presented. Grids coated with staphylococcal protein A were floated on samples mounted on agar containing 2% antiserum and incubated at 37 C, for 60 min. After washing and staining, the grids were observed in an electron microscope. The effects of protein A on virus detection were evaluated using poliovirus and bovine rotavirus infected cell culture fluids. The results showed that the technique using protein A (PA‐SIA) had at least 10‐fold higher sensitivity for virus detection than the original SIA. The optimal concentration of protein A was 1 to 10 μg/ml for coating the grids to trap virus particles. The PA‐SIA method was also compared with immunosorbent electron microscopy (ISEM). The former showed higher or at least the same sensitivity and some advantages in detecting antigen‐antibody reaction than the latter method. These results indicate that our PA‐SIA method may be superior to other IEM techniques presented previously for the detection and identification of viruses.


title: The integral membrane protein from a virulent isolate of transmissible gastroenteritis virus: molecular characterization, sequence and expression in Escherichia coli

text: Subgenomic mRNA from a virulent isolate of porcine transmissible gastroenteritis virus (TGEV) was used to produce cDNA clones. Part of a new clone and a previously reported clone were sequenced and used to construct the viral gene for integral membrane protein. A single open reading frame (ORF) encoding a polypeptide of 262 amino acids, relative molecular mass (M(r)) 29459, was identified. The positive identification of the polypeptide as the integral membrane protein was demonstrated by the production in E. coli of a chimaeric protein comprising most of the ORF encoding the M(r) 29459 polypeptide and β‐galactosidase. The chimaeric protein reacted with a specific monoclonal antibody to viral integral membrane protein and antibodies raised against the chimaeric protein immune precipitated the viral protein. Comparison with the sequence of an avirulent isolate indicates amino acid residues that may be important in pathogenicity.


Looking Forward to Serving SID


title: Differential Expression of the Major Histocompatibility Antigen Complex (MHC) on a Series of Burkitt's Lymphoma Lines

text: We compared the expressions of class I and class II major histocompatibility antigen complex (MHC) on the surface of Jijoye and P3HR‐1 cells of Burkitt's lymphoma sublines. Jijoye cells had a large amount of class I and class II MHC antigens, whereas these antigens were less expressed on P3HR‐1 cells. On a subline of P3HR‐1 K cells the expression of class I antigen markedly diminished and class II antigen was undetectable. On the other hand, Jijoye, P3HR‐1, and P3HR‐1 K cell lines were confirmed to be Epstein‐Barr virus (EBV) nonproducer, low producer, and high producer, respectively. The chemical activation of EBV genome by treating P3HR‐1 cells with 12‐O‐tetradecanyl phorbol‐13 acetate (TPA) and n‐butyrate resulted in inhibition of the expression of class I and II antigens, while the addition of retinoic acid, an inhibitor of virus replication, blocked the decrease in the MHC antigen expression. These findings suggested that there might be an inverse correlation between the virus production and the expression of class I and II MHC antigens.


Australia was indeed the “lucky country” in the recent worldwide SARS epidemic


title: Sequence of the nucleoprotein gene from a virulent British field isolate of transmissible gastroenteritis virus and its expression in Saccharomyces cerevisiae

text: Subgenomic mRNA from a virulent isolate of porcine transmissible gastroenteritis virus (TGEV) was used to produce cDNA which was sequenced. Two non‐overlapping open reading frames (ORFs) were identified. The largest, encoding a polypeptide of 382 amino acids (relative molecular mass (M(r)) 43 483), was shown to be the viral nucleoprotein gene. The second ORF, found 3’to the larger ORF, encodes a polypeptide of 78 amino acids (M(r) 9068) which has yet to be assigned to a viral product. The nucleoprotein gene was expressed in yeast cells under the control of two types of yeast promoters: the constitutive PGK promoter, and the inducible GAL1 promoter. Yeast cells containing recombinant plasmids, with the nucleoprotein gene in the correct orientation, produced a polypeptide of M, 47000, identical to the viral product, that reacted with a specific monoclonal antibody.


title: Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2003–2004

text: This review is the third update of the original review, published in 1999, on the application of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings the topic to the end of 2004. Both fundamental studies and applications are covered. The main topics include methodological developments, matrices, fragmentation of carbohydrates and applications to large polymeric carbohydrates from plants, glycans from glycoproteins and those from various glycolipids. Other topics include the use of MALDI MS to study enzymes related to carbohydrate biosynthesis and degradation, its use in industrial processes, particularly biopharmaceuticals and its use to monitor products of chemical synthesis where glycodendrimers and carbohydrate–protein complexes are highlighted. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:273–361, 2009


title: The dual role of thymidine phosphorylase in cancer development and chemotherapy

text: Thymidine phosphorylase (TP), also known as “platelet‐derived endothelial cell growth factor” (PD‐ECGF), is an enzyme, which is upregulated in a wide variety of solid tumors including breast and colorectal cancers. TP promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis. Elevated levels of TP are associated with tumor aggressiveness and poor prognosis. Therefore, TP inhibitors are synthesized in an attempt to prevent tumor angiogenesis and metastasis. TP is also indispensable for the activation of the extensively used 5‐fluorouracil prodrug capecitabine, which is clinically used for the treatment of colon and breast cancer. Clinical trials that combine capecitabine with TP‐inducing therapies (such as taxanes or radiotherapy) suggest that increasing TP expression is an adequate strategy to enhance the antitumoral efficacy of capecitabine. Thus, TP plays a dual role in cancer development and therapy: on the one hand, TP inhibitors can abrogate the tumorigenic and metastatic properties of TP; on the other, TP activity is necessary for the activation of several chemotherapeutic drugs. This duality illustrates the complexity of the role of TP in tumor progression and in the clinical response to fluoropyrimidine‐based chemotherapy. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 6, 903–953, 2009


title: Hydrocephalus in Suckling Rats Infected Intracerebrally with Mouse Hepatitis Virus, MHV‐A59

text: After intracerebral inoculation of mouse hepatitis virus, MHV‐A59 strain, into 3‐ to 5‐day‐old Wistar rats, some survivors at 14 days postinoculation (p.i.) were found to lack the cerebral cortex and to have an accumulation of a considerable amount of cerebrospinal fluid. The virus titer in the brain increased exponentially after inoculation, reaching a maximum 4 to 6 days p.i. when immunofluorescence revealed virus‐specific antigen within neurons in the cerebral cortex. A small amount of infectious virus was also detectable 14 days p.i. when the cerebral anomaly was evident. This brain malformation causing hydrocephalus was due to cerebral damage by viral infection.


title: Ancestral acquisitions, gene flow and multiple evolutionary trajectories of the type three secretion system and effectors in Xanthomonas plant pathogens

text: Deciphering the evolutionary history and transmission patterns of virulence determinants is necessary to understand the emergence of novel pathogens. The main virulence determinant of most pathogenic proteobacteria is the type three secretion system (T3SS). The Xanthomonas genus includes bacteria responsible for numerous epidemics in agroecosystems worldwide and represents a major threat to plant health. The main virulence factor of Xanthomonas is the Hrp2 family T3SS; however, this system is not conserved in all strains and it has not been previously determined whether the distribution of T3SS in this bacterial genus has resulted from losses or independent acquisitions. Based on comparative genomics of 82 genome sequences representing the diversity of the genus, we have inferred three ancestral acquisitions of the Hrp2 cluster during Xanthomonas evolution followed by subsequent losses in some commensal strains and re‐acquisition in some species. While mutation was the main force driving polymorphism at the gene level, interspecies homologous recombination of large fragments expanding through several genes shaped Hrp2 cluster polymorphism. Horizontal gene transfer of the entire Hrp2 cluster also occurred. A reduced core effectome composed of xopF1, xopM, avrBs2 and xopR was identified that may allow commensal strains overcoming plant basal immunity. In contrast, stepwise accumulation of numerous type 3 effector genes was shown in successful pathogens responsible for epidemics. Our data suggest that capacity to intimately interact with plants through T3SS would be an ancestral trait of xanthomonads. Since its acquisition, T3SS has experienced a highly dynamic evolutionary history characterized by intense gene flux between species that may reflect its role in host adaptation.


Preventing local transmission of SARS: lessons from Singapore


SARS and its effect on medical education in Hong Kong