bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiallergic and Anti-Inflammatory Effects of a Novel IκB Kinase β Inhibitor, IMD-0354, in a Mouse Model of Allergic Inflammation
Authors: Sugita Akemi , Ogawa Hirohisa , Azuma Masahiko , Muto Susumu , Honjo Akifumi , Yanagawa Hiroaki , Nishioka Yasuhiko , Tani Kenji , Itai Akiko , Sone Saburo
Published: October 2008

Background: Nuclear factor (NF)-κB is a transcription factor known to regulate allergy-associated cytokine and chemokine production related to the induction of inflammation. IκB kinase β (IKKβ), which is responsible for activation of the NF-κB pathway, may be an ideal molecular target to inhibit this process. IMD-0354 [N-(3,5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide] is an attractive novel IKKβ inhibitor that prevents the production of inflammatory cytokines in various diseases, although it is not known if IMD-0354 is effective against allergic inflammation. This study aimed to elucidate the antiallergic effects of a newly synthesized IKKβ inhibitor, IMD-0354, in a mouse model of allergic inflammation. Methods: We generated ovalbumin (OVA)-sensitized mice which were then challenged with OVA. IMD-0354 was administered intraperitoneally to therapeutic groups. Lung histopathology and the concentrations of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and supernatants of lung homogenates were determined. Results: Administration of IMD-0354 ameliorated airway hyperresponsiveness and reduced the numbers of bronchial eosinophils and mucus-producing cells in OVA-sensitized mice. The total numbers of cells and eosinophils in BALF were also reduced by treatment with IMD-0354. Treatment with IMD-0354 inhibited the production of Th2 cytokines such as interleukin (IL)-5 and IL-13 and eotaxin in the airways and/or lungs of OVA-sensitized mice, but it did not affect the restoration of Th1 cytokines such as IL-12 and interferon-γ under the same experimental conditions. IgE production was also inhibited by IMD-0354. Conclusion: A specific IKKβ inhibitor, IMD-0354, improved allergic airway inflammation and hyperresponsiveness in mice. IMD-0354 may have therapeutic potential for bronchial asthma.
Serum Leptin Levels in Patients with Pollen-Induced Allergic Rhinitis
Authors: Ciprandi Giorgio , Filaci Gilberto , Negrini Simone , De Amici Mara , Fenoglio Daniela , Marseglia Gianluigi
Published: October 2008

Background: Several studies have outlined a possible relationship between an increased body mass index (BMI) and respiratory allergic diseases, such as asthma and rhinitis. The aim of the study was to evaluate the serum leptin levels in a cohort of patients with pollen-induced allergic rhinitis, enrolled outside the pollen season, and in a group of healthy controls. Methods: The study included 75 subjects: 41 patients with moderate–severe persistent allergic rhinitis due to a pollen allergy and 34 normal subjects. All subjects were prospectively and consecutively evaluated. A skin prick test and blood sampling for assessing serum leptin levels, eosinophils, specific IgE, and nasal challenge were performed in all subjects. Results: After analyzing genders separately, female allergic patients showed significantly higher levels than normal females (p = 0.031), whereas the comparison between allergic and normal males was not significant (p = 0.9651). Leptin serum levels were significantly related with age in normal (p = 0.0059) and allergic (p = 0.0042) females. In addition, BMI and leptin levels were significantly correlated (p = 0.01) in all allergic patients; there were other significant relationships between leptin levels and symptom severity in females (p = 0063, r = 0.68), peripheral eosinophils in males (p = 0.023, r = 0.49), and allergen threshold dose at nasal challenge in both genders (males: p = 0.0001, r = –0.85; females: p = 0.0001, r = –0.95). Conclusions: This preliminary study provides the first evidence of significantly higher leptin serum levels in female patients with pollen-induced allergic rhinitis outside the pollen season.
Immunoglobulin E-Dependent Regulation of the CCR3 Chemokine Receptor by Interferon-Gamma in Atopic Asthmatics
Authors: García-Vega Yanelda , Rodríguez-Perez Judith , Bermúdez-Badell Cimara , Blanco-Garcés Elizabeth , Valenzuela-Silva Carmen , López-Saura Pedro , Bello-Rivero Iraldo
Published: October 2008

Background: The chemokine receptor CCR3 mediates the migration of cells that play an important role in the pathogenesis of asthma to inflammatory foci. Interferon (IFN)-γ is known to downregulate the expression of some chemokine receptors. Therefore, we decided to analyze the regulation of CCR3 by IFN-γ in asthmatics and to characterize the dependence of this process on immunoglobulin E (IgE) levels. Methods: Atopic asthmatics were treated with IFN-γ or placebo, and the IgE concentration in the blood was measured using an ultra-micro-ELISA for total IgE. Mononuclear cells from patients and controls were isolated by Ficoll-Hypaque gradient and incubated in the absence or presence of IFN-γ for different periods of time. After incubation, the cells were washed and lysed for RT-PCR analysis, which was performed using a Perkin-Elmer kit. Results: IFN-γ treatment apparently improved the evaluated clinical variables; however, the differences were not significant compared to the placebo group. We found that IFN-γ downregulated CCR3 mRNA expression ex vivo and in vivo in those patients with IgE levels higher than 500 IU/ml, whereas IFN-γ upregulated CCR3 mRNA expression in patients with IgE levels lower than 500 IU/ml. Correspondence between ex vivo and in vivo results was observed using this approach. There was found to be a direct correlation between total serum IgE and CCR3 mRNA expression. Conclusions: In those asthmatic patients with high levels of IgE, who are thus susceptible to downregulation of CCR3 by IFN-γ, a significant therapeutic effect with systemic IFN-γ might be expected.
Analysis of Polymorphisms in Olive Pollen Allergy: IL13, IL4RA, IL5 and ADRB2 Genes
Authors: Llanes Elena , Quiralte Joaquín , López Esther , Sastre Beatriz , Chacártegui Marina , del Pozo Victoria , Palomino Pilar , Lahoz Carlos , Cárdaba Blanca
Published: October 2008

Background: Previous results demonstrated that sensitization to specific olive pollen allergens could be related with a different clinical pattern (asthma and/or rhinitis), and that specific patterns of sensitization are regulated by different HLA class II antigens. The authors analyze the possible implication of 7 genetic polymorphisms described as asthma susceptibility genes: IL13 (C–1112T and R130Q), IL4RA (I50V, Q551R), IL5 (C–746T) and ADRB2 (Q27E and R16G) in specific olive pollen allergic sensitization. Methods: The authors genotyped seven polymorphisms of the IL13, IL4RA, IL5 and ADRB2 genes in 146 patients allergic to olive pollen with seasonal rhinitis/asthma and 50 controls using the polymerase chain reaction-restriction fragment length polymorphism and real-time polymerase chain reaction techniques. Results: Two polymorphisms of IL13 were associated with allergy to olive pollen: the TT genotype of IL13 C–1112T was decreased (odds ratio, OR = 0.35, p = 0.006) whereas the RQ heterozygous genotype of IL13 R130Q increased in patients allergic to olive pollen (OR = 3.12, p = 0.009). The combined analysis of two IL4RA single nucleotide polymorphisms (SNPs) (I50V and Q551R) showed an association with asthma: IL4RA V50/Q551 was associated with risk (OR = 2.48, p = 0.007) whereas the IL4RA V50R551 haplotype was associated with protection (OR = 0.31, p = 0.003). Conclusions: The IL13 polymorphisms under study were associated with specific allergy to olive pollen: the IL13 C–1112T polymorphism as a protective factor and the IL13 R130Q polymorphism as a risk factor. Interestingly, although single polymorphisms of IL4RA are not associated with any phenotype analyzed, the interaction between IL4RA I50V/Q551R was strongly associated with the asthma phenotype. IL13 and IL4RA could be relevant markers for allergy to olive pollen and asthma development.
Molecular Events in Human T Cells Treated with Diesel Exhaust Particles or Formaldehyde that Underlie Their Diminished Interferon-γ and Interleukin-10 Production
Authors: Sasaki Yoshinori , Ohtani Tomoyuki , Ito Yumiko , Mizuashi Masato , Nakagawa Satoshi , Furukawa Toru , Horii Akira , Aiba Setsuya
Published: October 2008

Background: A series of epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) and formaldehyde (FA) may help trigger T helper type 2 (Th2)-mediated allergic responses. Methods: To identify the molecular events by which DEP and FA induce a Th2-skewed immune response, we stimulated T cells from healthy subjects with anti-CD3/anti-CD28 monoclonal antibodies and examined the effect of pretreatment with DEP or FA on mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB by Western blotting and colorimetric NF-κB assays. We also examined the mRNA expression profiles of the T cells by microarray and real-time PCR analyses. Results:FA selectively suppressed interferon (IFN)-γ and interleukin-10 mRNA expression and protein production in stimulated T cells, as we previously reported with DEP. In the present study, we found that both DEP and FA suppressed NF-κB signaling and activated MAPKs. Both also significantly suppressed the mRNA expression of T-bet, Txk and c-Maf. Microarrays revealed significant augmentation of the expression of 2 FoxO3a-dependent genes, namely glucocorticoid-induced leucine zipper and growth arrest and DNA damage-inducible gene 45α (Gadd45a), which are known to modulate T cell immune responses. Treatment with N-acetylcysteine reversed the augmented Gadd45a mRNA response and caused the suppressed IFN-γ mRNA response to recover. Conclusions:DEP and FA have similar transcriptional and nontranscriptional effects on T cell signaling that together promote a Th2-skewed immune response.
Safety and Immunogenicity of a Cluster Specific Immunotherapy in Children with Bronchial Asthma and Mite Allergy
Authors: Schubert R. , Eickmeier O. , Garn H. , Baer P.C. , Mueller T. , Schulze J. , Rose M.A. , Rosewich M. , Renz H. , Zielen S.
Published: October 2008

Background: Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy. Methods: A total of 34 children (6–18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgGMite and IgG4Mite, by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3. Results: There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgGMite (p < 0.001) and specific IgG4Mite (p < 0.001) significantly increased after 8 weeks, while it took 12 weeks in the classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups. Conclusion: Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients.
Asymptomatic Sensitization to Hymenoptera Venom Is Related to Total Immunoglobulin E Levels
Authors: Sturm Gunter J. , Schuster Christian , Kranzelbinder Bettina , Wiednig Michaela , Groselj-Strele Andrea , Aberer Werner
Published: October 2008

Background: The detection of specific serum immunoglobulin E (sIgE) to Hymenoptera venoms is an established diagnostic tool to diagnose insect venom hypersensitivity. However, the specificity of sIgE detection is a debated issue. Methods: In 145 subjects, total IgE (tIgE) and sIgE to Hymenoptera venoms as well as sIgE to rapeseed as a marker of cross-reactive carbohydrate determinants were measured. In addition, an atopy score was determined for each patient. We looked for a possible association between tIgE and the presence of sIgE in subjects with a negative history of large local or systemic reactions to insect stings. Results: Fifteen of 65 subjects (23.1%) with low levels of tIgE (<50 kU/l) had sIgE for bee or wasp venom, and 23 of 47 subjects (48.9%) with a tIgE from 50 to 250 kU/l showed sIgE. The highest rate of asymptomatic sensitization (22 of 33; 66.7%) was found in patients with tIgE levels higher than 250 kU/l. Median sIgE was approximately 4.8 times higher in subjects with tIgE levels above 250 kU/l than in those with tIgE levels <50 kU/l. Interestingly, a significant difference in median tIgE was recorded between individuals with and without sIgE to rapeseed [776.5 kU/l (25, 75% percentiles: 252.5, 2,000.0) vs. 50.5 kU/l (20.1, 172.0), respectively; p < 0001]. Conclusion: Specific antibodies are frequently seen in individuals with high tIgE, but appear to be largely irrelevant in clinical terms. This might lead to misdiagnosis in persons with an inconclusive sting history.
Alcohol Exposure and Cognitive Development: An Example of Why We Need a Contextualized, Dynamic Life Course Approach to Cognitive Ageing – A Mini-Review
Authors: Anstey Kaarin J.
Published: October 2008

Background: A substantial literature exists that demonstrates associations between putative risk factors and cognitive decline in late life. However, there is a need to integrate this broad literature within a framework that incorporates the interaction of behavioral and ecological influences with cognitive development. Such a framework is required for developing a range of personal and environmental interventions to optimize cognitive development in the population, and to reduce the risk of cognitive impairment in late life. Objective: This review aims to identify the key considerations for developing a life course model of the various factors that influence cognitive development and cognitive decline. A contextualized, dynamic approach to life course epidemiology is proposed. Methods: A theoretical evaluation of key methodological and interpretational issues relating to how risk factors influence cognitive development and cognitive impairment was conducted. This focused on the example of alcohol consumption as a risk factor for cognitive decline and dementia. Results: This review identified dimensions that need to be accounted for in life course theories of cognitive development and cognitive impairment. These include: (a) intergenerational influences; (b) methodological and interpretational issues; (c) individual differences (personal factors); (d) contextual factors (environmental or ecological factors), and (e) cognitive ability as determinant. The methodological and interpretational factors included measurement of exposure and outcome variables; the important distinction between level of ability versus change over time; nonlinear relationships among exposures and outcomes, and outcomes and age; the distinction between association and cause, and between short-term effects and long-term change. Conclusion: A contextualized, dynamic approach to life course epidemiology accounts for the complex range of influences over the life course that interact to determine normal and pathological cognitive ageing. This approach provides a framework for the development of interventions to maximize cognitive gains in early life, and minimize cognitive loss in late life.
lin– Sca-1+ Cells and Age-Dependent Changes of Their Proliferation Potential Are Reliant on Mesenchymal Stromal Cells and Are Leukemia Inhibitory Factor Dependent
Authors: Schraml Elisabeth , Fehrer Christine , Brunauer Regina , Lepperdinger Günter , Chesnokova Vera , Schauenstein Konrad
Published: October 2008

Aging as a process is paralleled by a variety of hematological alterations. Characteristic features are a diminished homeostatic control of blood cell production and a decline in immune functions. It is generally accepted that stromal cells play a basal role in hematopoiesis by providing survival and differentiation signals, by secreting cytokines, or through direct contact with hematopoietic stem cells, thereby supporting the generation and replenishment of hematopoi- etic progenitor cells (HPC). Here we demonstrated that HPC-related colony formation is positively influenced by mesenchymal stromal cells (MSCs) when grown in co-culture, in particular regarding the number of primary granulocyte/macrophage colony-forming units as well as with respect to the average size of the formed colonies. These effects were more pronounced when the MSCs originated from young donors than from old ones. Because leukemia inhibitory factor (LIF) plays an important role during hematopoiesis, properties of lin– Sca-1+ cells and MSCs derived from LIF-deficient mice (LIF–/–) were determined both ex vivo and in vitro. LIF–/– animals contain a significantly reduced number of lin– Sca-1+ cells, nevertheless the replating capacity of LIF–/– HPCs was found to be generally unchanged when compared to those from LIF+/+ animals. However, when cocultured with MSCs, LIF–/– lin– Sca-1+ cells exhibited comparable characteristics to HPCs derived from old wild-type animals.
Efficacy of ER-α Polymorphisms and the Intrafollicular IGF System for Predicting Pregnancy in IVF-ET Patients
Authors: Choi Young Sik , Kim Seok Hyun , Ku Seung-Yup , Jee Byung Chul , Suh Chang Suk , Choi Young Min , Kim Jung Gu , Moon Shin Yong
Published: October 2008

Aims: To evaluate the efficacies of the estrogen receptor-α (ER-α) gene polymorphisms and of the intrafollicular insulin-like growth factor (IGF) system for predicting pregnancy in in vitro fertilization and embryo transfer (IVF-ET) patients. Methods: A total of 96 patients undergoing IVF-ET were included in this study. Genotyping for the ER-α gene PvuII and XbaI polymorphisms was performed using polymerase-chain reaction and single base extension method. Follicular fluid (FF) IGF-I, IGF-II, and IGFBP-3 concentrations were measured by RIA, and IGFBP-4 by ELISA. We compared, between pregnant (n = 28) and non-pregnant groups (n = 68), the allele frequency, genotype distribution and haplotype distribution of PvuII and XbaI polymorphisms, and then FF IGF-I, IGF-II, IGFBP-3, IGFBP-4 concentrations and their ratios. Results: No significant differences were found between the two groups in terms of allele, genotype or haplotype distributions of the ER-α gene PvuII and XbaI polymorphisms between the two groups. The mean FF IGF-I/IGFBP-3 ratio was significantly higher in the pregnant group (5.9 ± 1.5 vs. 4.8 ± 1.5 ×10–2). Conclusions: The intrafollicular IGF-I/IGFBP-3 ratio of the FF of the dominant follicle during oocyte retrieval appears to be related to the establishment of pregnancy in IVF-ET patients, whereas the ER-α gene PvuII and XbaI polymorphisms do not.
Association of the Apolipoprotein E Gene, Its Promoter Polymorphisms and Haplotypes with Depressive Symptoms
Authors: Elovainio Marko , Puttonen Sampsa , Pulkki-Råback Laura , Kivimäki Mika , Viiri Leena E. , Lehtimäki Terho , Karhunen Pekka , Viikari Jorma , Raitakari Olli T. , Keltikangas-Järvinen Liisa
Published: October 2008

Objectives: Evidence on apolipoprotein E (APOE) gene as a vulnerability factor for depression is mixed. Polymorphisms of the APOE gene regulatory region may serve as additional explanatory factors, as they help in explaining variation of depressive symptoms within the APOE Ε2/Ε3/Ε4 genotype groups. In this study, the associations of the APOE gene promoter polymorphisms –219G/T and +113G/C and their haplotypes with depressive symptoms were examined. Methods: The data is from a subpopulation of 660 young adults (24–39 years old) of the ongoing population-based Cardiovascular Risk in Young Finns Study. Depressive symptoms were assessed by a revised version of Beck’s Depression Inventory. Clinical screening assessed lipid levels and other known physiological and behavioral risk factors for depressive symptoms. Results: The APOE Ε4 allele was not related to depressive symptoms. Similarly, no statistically significant associations were found between the APOE gene promoter –219G/T and +113G/C polymorphisms and depressive symptoms. Within theAPOE Ε3/Ε3 genotype subgroup (n = 373), carriers of both –219G/+113C and –219T/+113G haplotypes (GC/TG) had higher depressive symptoms compared to noncarriers of these haplotypes (2.52 vs. 1.98; p = 0.002). This relationship persisted after separate adjustments for various risk factors including sex, age, LDL cholesterol, HDL cholesterol, triglycerides, total cholesterol, C-reactive protein, systolic blood pressure, body mass index and alcohol consumption. Conclusions: Our results suggest that the APOE gene does not predispose carriers to depressive symptoms among healthy young adults. However, the promoter haplotype GC/TG may elevate the risk of depressive symptoms.
Brain-Derived Neurotrophic Factor Val/Met Polymorphism and Bipolar Disorder
Authors: Kim Byungsu , Kim Chang Yoon , Hong Jin Pyo , Kim Seong Yoon , Lee Chul , Joo Yeon Ho
Published: October 2008

Background/Aims: The substitution of valine by methionine in the brain-derived neurotrophic factor (BDNF Val/Met) gene alters the intracellular trafficking and regulated secretion of BDNF. This study tested whether the BDNF Val/Met polymorphism is associated with bipolar disorder in Korean subjects, and whether clinical features vary according to genotype. Methods: The allelic and genotypic distributions of BDNF Val/Met were determined in a population of 169 bipolar patients and 251 normal controls. Between-genotype comparisons of clinical features were performed without a priori knowledge of the genotype of individual patients. Results: Allelic distributions did not differ significantly between bipolar patients and controls (χ2 = 0.400, p = 0.821). However, the rate of suicide attempts among the Val/Val (11.3%), Val/Met (28.8%) and Met/Met (38.9%) genotype groups were significantly different (χ2 = 9.879, p = 0.007). Relative to patients with the Val/Val genotype, those with the Met/Met genotype had a 4.9-fold higher risk of suicide attempts (95% CI, 1.7–14.7). Conclusions: These findings suggest that BDNF Val/Met is related to the suicidal behavior of bipolar patients, and may have clinical relevance as a biological indicator of bipolar patients at risk of suicide.
Cells Involved in the Immune Response
Authors: Haasz R. , Richter M.
Published: October 2008

It has been shown that extirpation of the thymus, the spleen, and the SAPP organs (appendix, sacculus rotundus and Peyer’s patches) in the normal adult rabbit does not affect the capacity of the rabbit to mount a humoral immune response to either particulate (SRBC or HRBC) or soluble protein (HSA or BGG or OA) antigens. Since it has previously been shown that the bone marrow does not constitute the organ capable of providing the host with the antibody-forming cells (AFC), it is concluded that no single lymphoid organ in the immunologically mature rabbit at the time of immunization constitutes the source of virgin AFC or serves as a necessary site of maturation of the AFC. Furthermore, the spleen, thymus and SAPP organs do not appear to possess any hormonal function with respect to the maintenance of immunocompetent cells. It is assumed that no single lymph node or the unorganized lymphoid cell accumulations or infiltrations would possess this unique role. It is, therefore, postulated that either all the lymphoid organs in the mature, adult rabbit possess virgin AFC or that the AFC represents a transient stage of morphological development of a potentially immunocompetent population of lymphocytes. Evidence has been presented that these cells, ontogenetically, probably arise in the gut-associated (SAPP) lymphoid organs and disseminate and infiltrate the other lymphoid organs either prenatally or in the early postnatal period.
Demonstration by Electron Microscopy of Viruses in Cells Found by Light Microscopy to Contain Inclusion Bodies
Authors: Rossi G.L. , Pauli B. , Luginbühl H. , Probst D.
Published: October 2008

Recently, a method was developed in this laboratory by means of which inclusion bodies found in cells during examination of histological sections might be processed for electron microscopy and by which the presence or absence of viruses in these bodies would be determined. The results of applying this method to the inclusion bodies of psittacosis, canine infectious hepatitis, equine viral rhinopneumonitis, bovine rabies and canine distemper are described. These demonstrate that definitive diagnosis can be established by this method.
L’atteinte du tissu cellulo-adipeux dans la tuberculose expérimentale de la souris
Authors: Mauss H. , Levy F.M.
Published: October 2008

The intravenous injection of tubercle bacilli in mice results in the deposition of many bacilli in adipose tissue. This implantation occurs earlier in brown fat than in white fat. It does not follow immediately after the injection, but results from the redistribution of some of the bacilli which are, at first, stopped in the lungs. The bacillary multiplication leads to the formation of scattered lesions, which consist of local mesenchymal and adipose cells, joined by macrophages of circulatory origin. The nodular picture appears similar to the pulmonary one, but progresses more slowly. The effects of immunity after a previous immunization are especially noteworthy-, limited bacillary multiplication, delayed necrosis and extensive cellular metaplasia. The involvement of cellular adipose tissue, and in general of mesenchymal tissue, until now little known, doubtlessly plays an important part in the evolution of experimental tuberculosis.
Comparison of Complement – Fixation and Immunodiffusion Tests for the Detection of Hepatitis-Associated Antigen
Authors: Papaevangelou G.J. , Tsoukas S.
Published: October 2008

Hepatitis-associated antigen (HAA) was detected by immunodiffusion (ID) or complement-fixation (CF) test in 141 (47.3%) of 298 viral hepatitis patients. 35 cases were positive by the CF test only, while 2 cases by ID test only. However, CF test failed to detect HAA in a greater number of sera from 60 studied leprosy patients. CF HAA titers were highly correlated, but 15–25 times higher than ID titers. The increased sensitivity of the CF test especially in cases with low HAA titers may be the reason for the observed greater decline of the relative frequency of HAA, in relation to time of collection of sera after onset of jaundice, when sera were examined by ID rather than by CF test. In 39 (28.1%) cases, positive by the CF test, prozone reactions were observed at dilutions of 1 : 16 or higher, which stresses the necessity to examine a wide range of serum dilutions. The presence of anticomple-mentary activity had no diagnostic value and did not interfere substantially with the detection of HAA.
Intracellular Antigens of Streptococcus pyogenes
Authors: Havlíček J. , Havlíčková Helena
Published: October 2008

Five antigens were identified in intracellular material from Streptococcus pyogenes cells. The antigens were isolated by trypsin treatment and subsequent gel filtration on Sephadex G-200. They were then purified by chromatography on DEAE Sephadex A-50.
Schistosome Ova Deposits in the Appendix
Authors: Schmid H.
Published: October 2008

A histopathological analysis is given of 20 appendices harbouring schistosome ova. 6 showed frank schistosome-specific lesions permitting the diagnosis of bilharzial appendictis. Within the group of 10 cases with chronic specific bilharzial reactions, one-half, coupled with pyogenic inflammation, differed from the frankly specific chronic group in the pattern of ovidistribution and specific inflammatory reaction. The significance of these findings is discussed in the light of possible chronic endogenous desensitization. Specific and non-specific pathogenic mechanisms are demonstrated as contributing influences to this form of appendicitis, which is primarily of a parasitical nature.
Loss of Protective Activity of BALB/c Spleen Homogenate against Cell-Free Transmission of HIPA-Plasmacytoma by Pretreatment with Mineral Oil of Spleen-Donor Mice
Authors: Pedio G. , Rüttner J.R. , Odermatt B.F.
Published: October 2008

A significant loss of protective activity of BALB/c spleen homogenate against cell-free transmission of HIPA plasmacytoma was noted by pretreatment with mineral oil of spleen donor mice. No decrease of protection was found in ICR mice, when they received intraperitoneally spleen homogenate from oil-pre-treated BALB/c mice. A strain specific immunosuppression, combined with virus activation, could be the mechanism of this effect.
Latent Adenosine Deaminase Activity in Rat Brain
Authors: Mustafa S.J.
Published: October 2008

Treatment of whole rat brain homogenate with Triton-X-100 resulted in a significant increase in adenosine deaminase activity. These studies point towards the existence of latent form of adenosine deaminase in rat brain mitochondria.
Neurosecretory System Function of Guinea Pigs under Influence of Staphylococcal Alpha Toxin
Authors: Kwarecki K. , Szmigielski S. , Jeljaszewicz J.
Published: October 2008

The experiments were performed on guinea pigs injected intraperitoneally with 20 µg/kg of purified staphylococcal alpha toxin. Fifteen minutes later, the animals received tritiated uridine or methionine in the dose of 1 µCi/kg and were killed 2,24 and 72 h after injection. The hypothalamus, with the supraoctical nucleus region, and the hypophysis were taken for histological procedure. Slices were covered with radioautographic Kodak AR-10 stripping film and exposed in darkness for a few weeks. The number of labeled cells and the number of silver grains above nuclei and cytoplasma were counted. Only a slight increase in incorporation of uridine was found in the experimental animals as compared to the control group, while a markedly higher number of silver grains was found in the animals treated with methionine. This increase of grains in the methionine-treated animals was followed by much quicker lowering of labeling at 72 h, compared to the control group. The obtained results suggest stimulation of the neurosecretory system under influence of staphylococcal alpha toxin.
Articular Aging and Osteoarthrosis in Dwarf Mice
Authors: Silberberg Ruth
Published: October 2008

In aging hypopituitary dwarf mice (dwdw), articular chondrocytes are poorly supplied with organelles; aggregation of collagen in the cartilaginous matrix is decreased, and aging of the articular cartilage is retarded as compared to non-dwarf mice (Dwdw or DwDw) of the same strain. Osteoarthrosis developing in 58% of male and in 22 % of female non-dwarfs was not observed in dwarfs regardless of sex. The unusually long life span of dwarf mice suggests that in hypopituitarism aging of non-skeletal tissues is likewise retarded.
Über eine Methode zur schnellen Bestimmung plaquebildender Einheiten von Parainfluenzaviren der Typen 2 und 3
Authors: Döhner L. , Herrmann R.
Published: October 2008

A plaque test for parainfluenza viruses types 2 and 3 is described which yields results within 4 and 2 days, respectively. Infectious centers forming under a semisolid layer of agarose are developed by hemadsorption followed by a benzidine reaction.
Comparative Study of CNS Lesions Induced by Tick-Borne Encephalitis Virus in Normal and X-Irradiated White Mice
Authors: Vince V. , Grčević N. , Stanković V.
Published: October 2008

Two dose levels of a tick-borne encephalitis virus were injected into normal and sublethally X-irradiated (450 r) mice. Radiation exposure resulted in marked changes in all parameters observed: (1) duration of sickness was prolonged so that irradiated mice also survived longer, although they were considerably less resistant to the lethal effect of injected virus suspensions; (2) antiviral antibodies were absent in blood of irradiated mice until the latest phase of sickness, when they occurred in a few animals only; (3) histological changes in the brains of irradiated animals showed absence of cellular reactivity and of other features of classical encephalitic process and were characterized by a diffuse encephalopathic picture. Slight appearance of microfocal inflammatory lesions was observed only in the late stages of the disease, or at the time of spontaneous death. The full classical picture of meningoencephalitis, which occurred in nonirradiated groups of animals, was never found in X-irradiated mice. Since it is, therefore, very probable that the observed changes were induced by immunosuppressive effects of X-rays, we assume that the development of the classical picture of encephalitis is a result of immunologic reaction of the host to the virus in the central nervous system.
Fibronectin Distribution Pattern and the Three-Dimensional Growth Behavior of Mammalian Cells under Anchorage-Independent Conditions
Authors: Rajaraman R. , Lonergan K.
Published: October 2008

Several types of normal diploid cells, established ‘normal’ cells, and transformed cells of human and rodent origin have been studied with reference to cell surface fibronectin distribution and their anchorage-independent growth behavior. All cell types that showed intercellular and fibrillar surface fibronectin were anchorage-dependent for growth. Lack of surface fibrillar fibronectin in spontaneously or virus-transformed cells and cells of neoplastic origin was accompanied by anchorage-independent growth potential. The degree of three-dimensional organization of cells under anchorage-independent growth conditions was dependent on the amount of intercellular fibronectin. The significance of these observations to in vivo tumor growth is discussed.
Studies on a Human Melanoma X Hamster Hybrid Line Selected by Metastasis
Authors: Watkins J.F. , Burns G.B. , Steplewski Z.
Published: October 2008

A highly metastatic hybrid line of human melanoma and tumourigenic, poorly metastatic hamster cells (BHK-21) was selected by pulmonary metastasis after injection of a fusion mixture into a Syrian hamster. The in vivo growth properties, karyotype, and plasminogen activator production of the line are reported. Monoclonal antibodies against the line indicated that it was expressing at least 8 human antigens although no melanoma-specific antigens were detected.
Natural Cytotoxicity against Chemically Induced Neurogenic Rat Tumors
Authors: De Bernardo E.
Published: October 2008

The 51Cr cytotoxicity assay was modified for ethylnitrosourea (ENU) and methylnitrosourea (MNU) induced rat neurogenic tumor cell lines. Investigations on ‘immune’ lymphoid cytotoxicity showed little cytotoxicity above normal. Alteration in the level of lymphocytotoxicity was seen immediately after injection of a highly immunogenic tumor (EA-528). Natural cytotoxicity (NC) was present against all neurogenic tumor cell lines tested and xenogenic cell lines. The level of NC activity was dependent on age, specific tumor cell line and could be increased by isolating the nylon wool non-adherent ‘T’ cell population. Allogenic WFu rat lymphocytes were tested for NC activity in vitro against CDF tumor cells. NC activity has potential use against these tumors in vivo.
An Unusual Arrangement of Smooth Membranes in the Root Meristem Cells of Allium cepa L. following Exposure to Colchicine
Authors: Witkus R. , Herold L. , Vernon G.M.
Published: October 2008

The unusual membranes in the root meristem cells of Allium cepa after exposure to colchicine are arranged in a closed multilayered structure consisting of a pair of double unit membranes enclosing a ground substance which consists essentially of ribosomes. The spaces between the unit membranes and between the pairs of unit membranes are uniform throughout the entire organelle. There is some indication of the association of this organelle with mitochondria.
Tumor-Promoting Diterpene Esters Prevent Macrophage Activation and Suppress Macrophage Tumoricidal Capacity
Authors: Keller R. , Keist R. , Adolf W. , Opferkuch H.J. , Schmidt R. , Hecker E.
Published: October 2008

The efficacy of varied diterpene ester type tumor promoters in suppressing the acquisition as well as the manifestation of cytolytic activity by macrophages was investigated. These mechanisms, believed to be basic to natural antitumor resistance, were markedly suppressed not only by the phorbol ester, TPA, but also by several other tumor promoters of the polyfunctional diterpene ester type covering tigliane, ingenane, and daphnane derivatives. The promoters were particularly effective in preventing the lymphokine-induced enhancement of natural cytolytic activity in resting macrophages. Moreover, the same promoters suppressed the manifestation of cytotoxicity by previously activated macrophages. Their influence on the effector phase was less pronounced than on the activation phase. In sharp contrast, typical solitary carcinogens of the polycyclic aromatic hydrocarbon type exerted little or no activity in the macrophage test systems. Since TPA had already been shown to suppress the natural killer activity in vitro and to abrogate host tumor resistance in vivo, the present findings lend further support to the interpretation that tumor promoters, apart from directly stimulating the outgrowth of transformed cells, may function via interference with natural antitumor effector systems.
Histopathologic Changes in the Peripheral Lymphoid Organs of Athymic Nude Mice Transplanted with Human Tumor
Authors: Kyriazis Andreas P. , Kyriazis Aikaterini A.
Published: October 2008

Lymph nodes of tumor-bearing nude mice were evaluated histologically and were found to differ significantly from those of nontumor-bearing control animals. Microscopically, the observed changes were classified into three patterns, namely histiocytosis, plasmacytosis and formation of germinal centers. The majority of tumor-bearing (63%) showed marked histiocytosis which was either diffuse or nodular involving primarily lymph nodes draining the site of the tumor. Plasmacytosis, affecting lymph nodes at various anatomical sites, was evident in 43% of mice, and in 37% of animals formation of germinal centers was observed. Germinal center formation was always associated with plasmacytosis and markedly increased IgG, IgM and IgA serum levels. There was no repopulation of the thymus-dependent areas by lymphocytes and graft-versus-host reaction was absent.
Transplantation and Metastasis of NB Rat Prostate Neoplasia in Congenitally Athymic (Nude) Mice, Nude Mice Treated with Antilymphocyte Sera and Congenitally Athymic Rats
Authors: Gershwin M.E. , Ruebner B.H. , Ikeda R.M.
Published: October 2008

The androgen-dependent NB rat prostate adenocarcinoma 2PR 129 and the autonomous tumor 102PR were transplanted into groups of both male and female nude mice, nude rats, and NB rats. Significant growth of the 2PR 129 tumor at the site of transplantation was noted in male but not female nude mice, nude rats or NB rats. Indeed, successful transplantation of 2PR 129 was not achieved in female nude mice even with usage of antilymphocyte sera. In contrast, the autonomous tumor 102PR grew at a significant rate at the local site of transplantation in mice and rats of both sexes. Although significant tumor masses were found at the injection site of male nude mice transplanted with 2PR 129 and in both male and female nude mice injected with 102PR, metastasis was not found. Further, antilymphocyte sera increased the rate of growth of both tumors in nude mice but did not change the apparent metastatic potential. Nonetheless, metastasis was readily observed in male nude rats transplanted with 2PR 129 and nude rats of both sexes transplanted with 102PR. Such metastatic lesions of nude rats were found in lung, liver and kidney with a similar frequency and histologic profile as NB rats. These results suggest that the nude rat, at least for this rat tumor system, is a more versatile and biologically relevant system than nude mice and further cautions against use of xenotransplants as models of tumor natural history. Moreoever, it suggests the possible relationship between host recognition of species-determined genetic loci and metastatic potential.
Inhibitory Effect of Cytochalasin H on Cell Reaggregation of the Fresh Water Sponge, Ephydatia meyeni Carter
Authors: Ghaskadbi Surendra , Mulherkar Leela
Published: October 2008

Cytochalasin H (CH) has been shown to inhibit the reaggregation of dissociated cells of a fresh water sponge. The effect is dose-dependent and reversible. Even after 24 h of CH treatment, the cells show the formation of pseudopodia suggesting that the effect of CH may not be due to arrested cell motility. Exogenously added α-D-glucosamine, a precursor of complex carbohydrates, brings about reaggregation of CH-treated cells. Fluorescent Con A binding, both patching and capping, is shown by untreated as well as CH-treated cells. It is likely that CH, like cytochalasin B, may interfere with the production, release or binding of carbohydrate-containing macromolecules important in cell aggregation.
Changes in Energy Metabolism during the Early Development of Xenopus laevis
Authors: Løvtrup-Rein H. , Nelson L.
Published: October 2008

Xenopus embryos at various developmental stages were incubated in the presence of labelled substrates and the 14CO2 production determined. From the rates of oxidation of glucose labelled in positions 1 and 6 and from that of radioactive acetate, pyruvate and glutamate, it was concluded that the Embden-Meyerhof pathway and the Krebs cycle are functional during early embryogenesis, but that their relative participation in the metabolic processes is limited and increases from gastrulation onwards. Early development is characterized by the predominance of the pentose cycle and the glutamate-aspartate cycle. Furthermore, it was shown that glutamate may be the main energy source up to gastrulation.
The Role of Cell Surface Proteins in the Induction of Histogenetic Differentiative Responses by Some Human Breast Tumours and Hamster Tumours Implanted into Chick Embryos
Authors: Lakshmi M.S. , Latner A.L. , Sherbet G.V.
Published: October 2008

Cells of human breast tumours and fibrocystic hyperplasia grown in culture, and three hamster tumours were implanted between the cell layers of 18-hour-old chick blastoderm. Their ability to induce histogenetic responses in the ectodermal and endodermal embryonic tissues was investigated. The surface proteins of these tumour cells were labelled by lactoperoxidase-catalysed radioiodination. It is shown that the ability to induce the histogenetic effects may be related to the expression of 265K (K= 103 daltons) and 233K proteins on the surface of human tumour cells and of 115K proteins on the hamster tumour cells. The antiproteinase, aprotinin, inhibits the induction of the histogenetic responses by and apparently also prevents the deletion of 115K proteins from the hamster tumour cells. It is therefore suggested that cell surface proteins are involved in the complex processes of interaction between embryonic and tumour cells and in the recognition by the embryonic cells of the tumour cells implanted into their midst.
Monoclonal Antibodies to Human Cytokeratins: Application to Various Epithelial and Mesothelial Cells
Authors: Lang Alois B. , Odermatt Bernhard F. , Ruettner Jacques R.
Published: October 2008

Immunohistological analysis of human tissue using monoclonal antibodies against cytokeratins, which are confined to cells of epithelial origin, is a valuable technique. Using human epidermal keratins as antigen, we prepared monoclonal antibodies against cytokeratins (ZK1, ZK7, ZK61 and ZK99) and against a desmosomal protein (ZK31). Immuno-histochemical staining of human skin sections using these antibodies showed a specific reaction with the epidermis: ZK1 stained the entire epidermis, ZK7 only the basal layer, ZK61 and ZK99 the suprabasal layers, and ZK31 the cellular interfaces. In order to test for antibody specificity, immunoblots with human epidermal and amnion epithelial cytokeratin polypeptides, as well as immunofluorescence microscopy of simple epithelia (glandular and simple columnar epithelia) were performed. ZK1, ZK61 and ZK99 reacted preferentially with cytokeratin polypeptides of stratified squamous epithelia and ZK7 recognized cytokeratins of stratified and simple epithelia. When the ZK antibodies were tested on mesothelial cells in pleural effusions, only ZK7 reacted with these cells. Biochemical analysis of cytokeratin accumulation in cells of primary and long-term cultures indicated that the cytokeratin pattern of mesothelial cells was quite unstable, while that of amnion epithelial cells showed only minor quantitative changes. The use of these antibodies to determine the epithelial origin of cells present in pleural effusions is proposed.
Cytoskeletal Proteins as Tissue-Specific Markers in Cytopathology
Authors: Puts J.J.G. , Vooijs G.P. , Huysmans A. , van Aspert A. , Ramaekers F.C.S.
Published: October 2008

Antibodies to intermediate filament proteins react in a tissue-specific manner and can be used to characterize tumor cells present in thin-needle aspirates from solid tumors, from palpable lymph nodes and cells present in samples from peritoneal and pleural effusions. From our studies so far the following conclusions can be drawn: (a) Polyclonal antisera to cytokeratins can identify carcinoma metastases in thin-needle aspirates from palpable lymph nodes and distinguish them from malignant lymphomas and nonmalignant lesions such as chronic lymphadenitis, which show only vimentin-positive cells, (b) Monoclonal antibodies to specific cytokeratin polypeptides are able to distinguish between different types of epithelial tumor metastases, i.e. metastases from adenocarcinomas and metastases from squamous cell carcinomas, (c) Cells present in peritoneal and pleural effusions can be partly characterized using intermediate filament antisera. We have found that metastatic adenocarcinoma cells from breast, ovary, endometrium, cervix, colon and stomach, as well as squamous cell carcinomas and malignant mesothelioma stain specifically with antibodies to cytokeratin while mesenchymally derived tumors such as malignant lymphomas, malignant melanomas, and fibrosarcomas, are positive for vimentin only, (d) Metastatic tumor cells of epithelial origin present in aspirates from human serous body cavity fluids may coexpress vimentin next to their original cytokeratin intermediate filaments. Benign mesothelial cells present in body cavity fluids frequently coexpress cytokeratins and vimentin. (e) Tumor cells present in thin-needle aspirates from solid tumors such as pleomorphic adenomas of the parotid gland can be identified as such because of their typical patterns of intermediate filament (co-)expression. Antibodies to the different components of the intermediate filament cytoskeleton can thus be helpful in cytopathologic diagnosis where a definitive diagnosis cannot be made on the basis of conventional cytologic features.
Loss and Reappearance of Transferrin Receptors in Human Leukemic Cell Lines
Authors: Petraki Hellen , Ioannides Constantin G. , Filli Stella , Papamichail Michail
Published: October 2008

Serum transferrin (the iron binding protein) exerts its iron carrier function at the cell surface after binding to the appropriate receptor (TrR). In this work it is demonstrated that differentiating agents induce loss of TrR from the surface of three leukemic cell lines (Molt-3, HL-60 and K-562). Loss of TrR correlates with change in morphology and induction of phenotypic markers of the differentiated cells. Removal of the differentiating agent from the culture is followed by reexpression of TrR on the cell surface. The data presented in this paper suggest that TrR may play a regulatory role in cell differentiation and malignant transformation.