bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of allogeneic and xenogeneic in vitro T‐cell proliferative responses in sensitized patients awaiting kidney transplantation
Authors: Oostingh Gertie J. , Davies Hugh F. S. , Andrew Bradley J. , Taylor Craig J.
Published: October 2003

Abstract:  Highly sensitized patients awaiting kidney transplantation may be potential candidates for future clinical trials using pig organ donors. Because of crossreactivity between human leucocyte antigens (HLA) and swine leucocyte antigens (SLA), such patients might have heightened T‐cell responses to porcine xenoantigens. We determined whether lymphocytes from allo‐sensitized patients displayed secondary (cyclosporine resistant) T‐cell proliferative responses against porcine xenoantigens. Lymphocytes from six non‐sensitized, seven sensitized [immunoglobulin G (IgG) panel reactive antibodies (PRA) 11 to 84%], 14 highly sensitized patients (IgG PRA > 84%) and 12 healthy individuals were tested [in the presence and absence of Cyclosporin A (CsA)] to determine their proliferative response to human (allogeneic) and to porcine (xenogeneic) stimulator cells. Lymphocytes from all study groups showed a strong proliferative response to allogeneic and xenogeneic stimulator cells with no significant difference between non‐sensitized and sensitized individuals. Addition of CsA (100 and 500 ng/ml) inhibited (>90%) proliferation of lymphocytes from all non‐sensitized patients to both allogeneic and xenogeneic stimulators. CsA was less effective at inhibiting proliferation of lymphocytes from sensitized patients and highly sensitized patients to allogeneic stimulators [29% (n = 21) and 50% (n = 42) respectively were resistant to CsA inhibition (100 ng/ml)]. In contrast, cyclosporine inhibited proliferation of lymphocytes from the majority of sensitized and highly sensitized patients to xenogeneic stimulator cells [14% (n = 21) and 14% (n = 42) respectively were resistant to CsA inhibition (100 ng/ml)]. HLA sensitized patients awaiting renal transplantation display cyclosporine resistant proliferative T‐cell responses to allogeneic stimulators but proliferative responses to xenogeneic stimulators are more amenable to suppression by CsA. This finding suggests that humoral sensitisation to HLA antigens is not necessarily indicative of a heightened in vitro T‐cell response to SLA antigens.
Subsyndromal symptoms assessed in longitudinal, prospective follow‐up of a cohort of patients with bipolar disorder
Authors: MacQueen Glenda M , Marriott Michael , Begin Helen , Robb Janine , Joffe Russell T , Young L Trevor
Published: October 2003

Background: Many patients with bipolar disorder (BD) do not regain full function following an acute illness episode, but the extent to which this impairment is the result of persistent symptoms has not been well established. This study examined factors associated with persistent subsyndromal symptoms in a well characterized group of BD patients who were prospectively followed for an average of 3 years.

Methods: Detailed life charting data from 138 patients with BD were reviewed. Patients were categorized into euthymic, subsyndromal or syndromal groups according to the clinical state during their most recent year of follow‐up. The three groups were then examined with respect to comorbidity, function and treatment received.

Results: Patients with subsyndromal symptoms had high rates of comorbid anxiety disorders, and were more likely to have increased rates of eating disorders as well. Patients with subsyndromal symptoms had lower global assessment of function (GAF) scores than euthymic patients, and had as many clinic contacts and medication trials as patients with full episodes of illness.

Conclusions: Persistent subsyndromal symptoms in BD patients are associated with high rates of comorbidity that is important to recognize and treat in order to optimize mood and functioning.
Thyrotoxicosis after complete or partial lithium withdrawal in two patients with bipolar affective disorder
Authors: Carmaciu CD , Anderson CS , Lawton CA
Published: October 2003

Objectives: To highlight and discuss thyrotoxicosis after lithium withdrawal as a potential complication of lithium therapy for bipolar disorder.

Case Reports: Both patients presented developed thyrotoxicosis, the first patient after stopping the lithium completely, and the second patient after a reduction in the lithium dose.

Conclusions: Clinicians should be alert to the possibility of thyrotoxicosis emerging when lithium is being completely or partially withdrawn. Such withdrawal could unmask a latent hyperthyroidism.
Intracerebroventricular administration of ouabain as a model of mania in rats
Authors: El‐Mallakh Rif S , Adnan El‐Masri M , Huff Mary O'Malley , Li Xiao‐Ping , Decker Sarah , Levy Robert S
Published: October 2003

Background: Human bipolar illness is characterized by mood state‐ and diagnosis‐associated abnormalities of cellular cation distribution and transport. These include reduced sodium pump activity and expression and increased intracellular sodium. If these alterations are related to the pathophysiology of the disease, rather than secondary or ancillary abnormalities, then one would expect that modeling of these changes in vivo would produce lithium‐preventable behavioral abnormalities.

Methods: Ouabain, a potent inhibitor of the sodium pump, was administered intracerebroventricularly to male rats previously fed lithium‐containing food or plain rat chow. Locomotion was then quantified in an open field.

Results: Ouabain increased locomotion 300% over baseline. Lithium pretreatment prevented the ouabain‐induced hyperlocomotion response.

Conclusion: Inhibition of central nervous system sodium pump with ouabain produces a plausible animal model of mania. This model may be useful for preclinical screening of potential mood stabilizers.
An Australian validation study of the temperament and character inventory
Authors: Parker G. , Hadzi‐Pavlovic D. , Parker K. , Malhi G. , Mitchell P. , Wilhelm K. , Austin M‐P.
Published: October 2003

Objective: To assess the validity of the temperament and character inventory (TCI) measure in an Australian sample.

Method: A sample of depressed subjects completed the TCI and a measure assessing personality disorder constructs (PDCs), while family members and psychiatrists also returned PDC ratings.

Results: Factor analyses generally supported the TCI constructs, when the temperament and character scales were analysed separately. Self‐reported PDC scores were validated against corroborative witness ratings and used to assess the TCIs concurrent validity. Validation analyses supported all TCI temperament scales, but the Self‐transcendence Character scale was unassociated with PDC scores. The remaining two character scales (i.e. cooperativeness and self‐directedness) were non‐specifically associated with all PDC scores.

Conclusion: Study results support the validity of the TCI scales, but question the best model for conceptualizing the TCI. It is suggested that two character scales quantify disordered functioning, while temperament scales quantify style, constructs that may be inter‐related or independent in individual subjects.
Properties of the temperament and character inventory in a Chinese sample
Authors: Parker G. , Cheah Y‐C , Parker K.
Published: October 2003

Objective: To determine the influence of language and culture on the temperament and character (TCI) measure in a Chinese sample.

Method: We translated the TCI into Mandarin and had a non‐psychiatric sample of Malaysian Chinese subjects complete the TCI at baseline and at a 1‐month retest, with subsets completing English or Mandarin versions alternatively or on both occasions. Analyses examine the TCI factor structure and any impact of language and culture on TCI scoring.

Results: We identified age, gender, occupation and language effects on TCI scale scores. Test–retest reliability was high and not compromised by language. Scale internal consistency was also high. Factor analyses of separate sets of TCI scales corresponded strongly to the structure identified in the TCI development studies.

Conclusion: The results indicate that TCI is likely to have applicability to Chinese subjects, and argue against properties being constrained by the English language or by western culture.
Gray matter features of schizotypal disorder patients exhibiting the schizophrenia‐related code types of the Minnesota Multiphasic Personality Inventory
Authors: Yoneyama E. , Matsui M. , Kawasaki Y. , Nohara S. , Takahashi T. , Hagino H. , Suzuki M. , Seto H. , Kurachi M.
Published: October 2003

Objective: Previous studies have suggested that several code types of the Minnesota Multiphasic Personality Inventory (MMPI) are useful markers for identifying schizophrenia. We hypothesized that schizotypal disorder (STD) patients with such schizophrenia‐related code types have the morphological brain abnormalities associated with schizophrenia.

Method: Voxel‐based morphometric analysis with statistical parametric mapping (SPM) 99 software was used to investigate the differences in brain morphology between 14 STD patients with the schizophrenia‐related code types of the MMPI and 28 normal individuals.

Results: The STD patients showed significantly decreased gray matter volume in the insular regions bilaterally and in the left entorhinal cortex, compared with the controls.

Conclusion: Our findings suggest that STD patients with the schizophrenia‐related code types have volume reductions in these regions as an endophenotype that overlaps with schizophrenia.
Schizophrenia and weight management: a systematic review of interventions to control weight
Authors: Faulkner G. , Soundy A. A. , Lloyd K.
Published: October 2003

Objective: Weight gain is a frequent side effect of antipsychotic medication which has serious implications for a patient's health and well being. This study systematically reviews the literature on the effectiveness of interventions designed to control weight gain in schizophrenia.

Method: A systematic search strategy was conducted of major databases in addition to citation searches. Study quality was rated.

Results: Sixteen studies met the inclusion criteria. Five of eight pharmacological intervention studies reported small reductions in weight (<5% baseline body weight). All behavioural (including diet and/or exercise) interventions reported small reductions in, or maintenance of, weight.

Conclusion: Weight loss may be difficult but it is not impossible. Given the inconsistent results, the widespread use of pharmacological interventions cannot be recommended. Both dietary and exercise counselling set within a behavioural modification programme is necessary for sustained weight control.
Quantitative cell and matrix changes in human humeral head osteoarthritic cartilage
Authors: Mori RYUJI , Ochi MITSUO , Sakai YASUO , Maniwa SOKICHI , Kawasaki KENZO
Published: October 2003

A new quantitative method was devised both to establish an objective standard for morphometric diagnosis and to determine the extent of degeneration in osteoarthritic cartilage. Eight normal and forty‐eight osteoarthritic humeral heads, subsequently confirmed by light microscopy, were obtained at necropsy. The articular cartilage was observed in situ with a laser scanning confocal microscope (LSCM) and morphometric measurements determined cell density (cells/mm), cell volume fraction (%) and mean cell volume (μ3). The osteoarthritic cartilages were classified according to the following four characteristics: increase in thickness, increase in cell volume fraction, decrease in cell volume fraction, and fibrous pannus. Deviations in cell density and cell volume fraction from normal means were calculated as extent of degeneration. Our present approach aims to provide valuable clues, such as objective stereological information and a unique reference for biochemical and traditional morphlogical analyses, that clinicians will be able to use in combination with other methods in order to establish a reliable diagnosis.
Sudden unexpected death as a consequence of indinavir‐induced nephropathy
Authors: Rajs JOVAN , Blaxhult ANDERS , Sundelin BIRGITTA
Published: October 2003

A 60‐year‐old male had tested in 1986, at age 46, positive for human immunodeficiency virus (HIV). In mid‐1996 he was started on a protease inhibitor regimen, which included indinavir, lamivudine and stavudine, and remained on this therapy until his death. In April 1999 he was hospitalized after a fainting episode. Although examination focusing on cardiac disease did not disclose any remarkable findings, he died suddenly one week after being discharged from hospital. At autopsy the kidneys were enlarged, with a total weight of 500 g, patchy pale gray and pinkish. Microscopy showed leukocytic cell casts in many of the tubules and collecting ducts. In many of these casts there were clefts left by crystals. In the interstitium, both in the cortex and the medulla, there was focal inflammation and fibrosis. Death was attributed to sudden cardiac dysfunction, probably ventricular fibrillation as a consequence of severe nephropathy with electrolyte disturbances. It is likely that kidney damage developed secondary to the indinavir treatment as indinavir can cause not only nephrolithiasis but also crystal‐induced acute renal failure.
V3 sequence analysis and biological characterization of HTV‐1 isolates from asymptomatic and early symptomatic Tanzanian individuals
Authors: Holm‐Hansen CAROL , Stern BEATE , Rustad SIREN , Shao JOHN , ÅSjÖ BIRGITTA
Published: October 2003

The aim of this study was to determine HIV‐1 V3 sequences, in vitro biological characteristics and co‐receptor usage of virus isolates from Tanzania. Virus was isolated from 14 of 17 samples investigated. Four of the isolates induced syncytia in MT‐2 cells and used the CXCR4 co‐receptor, while the remaining 10 isolates used the CCR5 co‐receptor characteristic of non‐MT‐2 tropic viruses. One of the four MT‐2 tropic isolates also used the CCR5 and CCR3 co‐receptors. Proviral DNA was detected in all 14 isolates and PCR products were subjected to DNA sequencing. Unambiguous V3 amino acid sequences were obtained from 11 amplificates. Phylogenetic analysis indicated that these sequences were divergent and clustered in HIV‐1 subtypes A, C or D. Sequences from the viruses that induced syncytia in MT‐2 cells presented characteristic V3 phenotype‐associated amino acids. Results of co‐receptor analysis are in concordance with the isolate phenotype as determined by replication and induction of syncytia in MT‐2 cells. The considerable diversity illustrated by a limited number of isolates from Tanzania is in accordance with reports from other regions of Africa.
Extrapleural solitary fibrous tumor: clinicopathologic study of 17 cases and molecular analysis of the p53 pathway
Authors: Morimitsu YOSUKE , Nakajima MASAYOSHI , Hisaoka MASANORI , Hashimoto HIROSHI
Published: October 2003

Solitary fibrous tumor (SFT) occurring at various extrapleural sites is sometimes difficult to diagnose because of its histologic variability. Although a solitary fibrous tumor is usually a slow‐growing tumor with favorable prognosis, a small number of malignant cases have been reported. In the present study, we examined the clinical behavior, histologic, immunohistochemical and molecular features of 17 cases of extrapleural SFT. Four tumors were located in the pelvic cavity, two in the nasal cavity, two were confined to the pulmonary parenchyma, and there was one each in the meninges, kidney, mediastinum, retroperitoneum, temporal region, neck, groin, buttock and thigh. Histologically, all the tumors were characterized by the presence of areas consisting of a proliferation of bland spindle cells with variable amounts of thick, often hyalinized or keloid‐like intercellular collagen bundles. Highly cellular areas were observed in three tumors, frequent mitoses in two, and cellular pleomorph‐ism and tumor necrosis in one each. All 17 tumors showed immunoreactivity to CD34 and 15 (88%) to bcl‐2 protein. The labeling indices of p53, mdm2 protein and Ki‐67 were generally low. PCR‐SSCP and a subsequent sequence analysis of the p53 gene disclosed point mutation at codon 161 in exon 5 in one of the 13 cases analyzed. According to follow‐up information, none of the patients had developed local recurrence or distant metastasis. Our results suggest that most extrapleural SFTs behave in a benign fashion even in a higher histologic grade group, and it is difficult to predict their clinical outcome. Complete surgical excision in order to obtain clear margins and long‐term follow‐up is advisable for patients with an extrapleural SFT.
Expression and localisation of IGF‐binding protein mRNAs in regenerating rat skeletal muscle
Authors: Jennische EVA , Hall CHRISTINA M.
Published: October 2003

The expression of the insulin‐like growth factor‐binding proteins (IGFBP) ‐3, ‐4, ‐5 and ‐6 was investigated in neonatal, in normal adult and in regenerating rat skeletal muscle. Semi‐quantification was done by densitometric scannings of Northern blots. The expression of all investigated IGFBPs, with the exception of IGFBP‐5, was higher in neonatal than in adult muscle. During postischaemic regeneration the expression of all IGFBPs increased, but with different time schedules. IGFBP‐3 increased transiently during the early phase of regeneration, while IGFBP‐4, ‐5 and ‐6 increased during the later phase of regeneration. In situ hybridisation on regenerating muscle showed that the expression of the various IGFBPs was cell specific; thus, IGFBP 3 was mainly expressed in macrophages, IGFBP‐4 in connective tissue, IGFBP‐5 in regenerating muscle cells, and IGFBP‐6 in muscle cells, connective tissue and endothelium. Ligand blotting, using 125I‐IGF‐I as the ligand, showed a number of bands ranging between 24 and 44 kDa. Samples from neonatal and regenerating muscle contained much higher levels of all IGFBPs than those from normal adult muscle. An ordered and cell‐specific expression of IGFBPs, allowing a strict regulation of IGF actions, is probably necessary to ensure an optimal regeneration process.
Autoantibody activity of the immunoglobulin secreted by a follicular B‐cell lymphoma
Authors: Barrios Y. , Plaza A. , Cabrera R. , DÍAz‐Espada F.
Published: October 2003

In patients with B‐cell lymphoma, only in rare cases a secreted paraprotein is found, and in very few of them an associated autoantibody activity has been demonstrated. Here we report the case of a patient with a low‐grade B‐cell lymphoma with a serum biclonal paraprotein (G,M)Λ. and severe erythroblastopenia. Indirect immunofluorescence studies of total serum revealed cytoplasmic (Hep‐2 cells) and extracellular matrix (rat tissue sections) staining, suggestive of a new specificity. After gel filtration of serum samples, only the IgM‐containing fraction showed the same pattern of staining. Tumor‐derived hybridomas expressed an unmutated V3–11 gene identical to that found in tumor samples and secreted an IgM immunoglobulin endowed with the same reactivity, which confirms the tumoral origin of the tissue‐reactive protein. The results suggest a link between the autoimmune condition in this patient and the novel specificity displayed by the tumor‐derived immunoglobulin.
Structural evidence for counter‐current flow in proximal tubules versus peritubular capillaries in the rat kidney
Authors: Faarup P. , Holstein‐Rathlou N. H. , HegedÜS V.
Published: October 2003

Background. In spite of the very high exchange of water and solutes between the proximal tubules and the peritubular capillaries, very little is known about flow directions in these two interrelated structures. We therefore developed a morphological technique suitable for the quantitative evaluation of a counter‐current system between the proximal convoluted tubules and the peritubular capillaries in rat renal cortex. Methods. In male pentothal‐anesthetized Wistar rats (body weight 200–250 g), India ink was injected into the aorta above the renal arteries, followed by instant freezing of the right kidney in isopentane at ‐165°C, and subsequent freeze‐substitution in alcohol. In microscopic slides from kidneys in which only 20–55% of the cortical peritubular capillary loops was filled with ink ‐ representing the arterial end of the capillaries ‐ and in which the proximal tubular segmentation could be identified in PAS‐stained sections, the segments of the convoluted proximal tubules were quantitatively compared with regard to the presence of ink‐stained and unstained peritubular capillaries in nephrons from the whole renal cortex. Results. In the microscopic specimens of the five animals used both the loops from the first segment (PI) of the proximal convoluted tubule and those of the second segment (P2) were systematically packed closely together, the transitional segment (P1–2) being interposed between the groups. Around the loops of P1, 8%±2% of the capillaries was stained with India ink. In contrast, surrounding the P2 loops 67%±5% of the capillaries contained ink, significantly exceeding that for P1 (p<0.01). Conclusion. Throughout the rat renal cortex, the most proximal fraction of the peritubular capillaries surrounds the second segments of the proximal convoluted tubules, while the first tubular segments are surrounded by the more distal fraction of the peritubular capillaries. Consequently, the flows in the peritubular capillaries and in the proximal convoluted tubules in the rat renal cortex are systematically arranged as a counter‐current system. This feature was previously identified only in superficial nephrons.
MAP2 and neurogranin as markers for dendritic lesions in CNS injury. An immunohistochemical study in the rat
Authors: Li Gui Lin , Farooque Mohammad , Lewen Anders , Lennmyr Fredrik , Holtz Anders , Olsson Yngve
Published: October 2003

We compared two staining methods for the demonstration of dendrites under normal and pathological conditions of the rat central nervous system. MAP2‐ and neurogranin immunohistochemistry was applied to samples from normal tissue, spinal cord subjected to graded compression trauma, cerebral cortex following contusion trauma, and brains with focal ischemic lesions induced by occlusion of the middle cerebral artery (MCAO). Normal rats showed MAP2 immunoreactivity in nerve cell bodies and dendrites of brain and spinal cord. However, neurogranin staining was present only in nerve cell bodies and dendrites of the normal brain, and not in the spinal cord.

Reduction of MAP2 immunoreactivity was seen in lesions of spinal cords subjected to compression trauma. Neurogranin staining was of no value in this experimental condition since it was not present under normal conditions. The brain contusions showed loss of both MAP2‐ and neurogranin immunoreactivity at the site of the lesion. MCAO resulted in an extensive loss of MAP2‐ and neurogranin staining in the ipsilateral hemisphere.

In conclusion, our study shows that MAP2 immunostaining is a sensitive method for identifying dendritic lesions of various CNS injuries in the rat. Neurogranin immunostaining is an alternative method for investigations of dendritic pathology in the brain but not in the spinal cord.
An in vivo replica study of microbial colonization in «rapid» and «slow» dental plaque formers
Authors: Zee Kwan‐Yat , Samaranayake Lakshman P. , Attström Rolf
Published: October 2003

The aim of the present study was to investigate the morphological features of supragingival plaque development in «rapid» and «slow» plaque formers using the replica technique. Forty‐nine healthy volunteers were screened for their plaque formation rate after 3 days of oral hygiene abstinence using the plaque index (PI). Five subjects with the highest mean PI and six with the lowest mean PI were selected as «rapid» and «slow» plaque formers, respectively. After a series of thorough prophylaxis and oral hygiene instruction, all subjects went through a 14‐day period of no oral hygiene to allow undisturbed plaque formation. Light body silicone elastomeric impressions were taken for the upper right central incisor of each subject on day‐0, 1, 3, 7, and 14. Positive replicas were then poured from the impressions using epoxy resin and observed under a scanning electron microscope. A more complex supragingival plaque structure was seen in the day‐1 and day‐3 replicas of the «rapid» group compared to the «slow» group. From day‐7 to day‐14, during the maturation period of supragingival plaque, no discernible differences were noted between the two groups. Quantitatively, the percentage of plaque coverage on the tooth surfaces was higher in the «rapid» group than in the «slow» group in day‐1 and day‐3 replicas. These observations indicate that the morphological and topographical features of supragingival plaque in «slow» and «rapid» plaque formers differ, especially in the early developmental phase.
The resistance of human monocyte‐derived macrophages to Chlamydia pneumoniae infection is enhanced by interferon‐gamma
Authors: Airenne Sari , Surcel Heljä‐Marja , Bloigu Aini , Laitinen Kirsi , Saikku Pekka , Laurila Aino
Published: October 2003

Chlamydia pneumoniae is an intracellular bacterium which commonly causes respiratory infections. Chronic infections have been associated with atherosclerosis and the organism has been detected in macrophages in the disease lesions. Growth of chlamydiae in different epithelial cell lines is restricted by interferon‐gamma (IFN‐γ), a monocyte activator produced by T cells. We have studied the influence of IFN‐γ on the growth and infectivity of C. pneumoniae in HL‐cells and human monocyte‐derived macrophages. Low concentrations of the cytokine significantly restricted the growth and productivity of C. pneumoniae in epithelial cells in vitro. In macrophages, however, no effect on the growth of the bacteria in infected cells was found, but high doses clearly restricted the production of infectious progeny. The results suggest that IFN‐γ participates in the resistance to C. pneumoniae. The bacterium is, however, still capable of infecting macrophages that are important in the pathogenesis of atherosclerosis and it may thus participate in the inflammatory process associated with the disease.
Septic arthritis caused by a gram‐negative bacterium representing a new species related to the Bordetella‐Alcaligenes complex
Authors: Kronvall Göran , Hanson Hanna‐Stina , Von Stedingk Lars Victor , Törnqvist Eva , Falsen Enevold
Published: October 2003

A knee‐joint exudate culture yielded on two occasions a gram‐negative bacterium. Regular methods for speciation did not provide an identification. The infection was successfully treated with ciprofloxacin. The unknown isolate, CCUG 36768, was subjected to further investigation, including 16S rDNA sequencing, protein profiling, cellular fatty acid analysis, and various biochemical tests, in order to produce a species identification. The 1469 bp‐long 16S rDNA sequence did not reveal identity with any known species sequence. CCUG 36768 clustered in a group of species, including Alcaligenes defragrans, Denitrobacter permanens, Taylorella equigenitalis, Alcaligenes faecalis, and four strains of Alcaligenes species without a specific species name. Bordetella species also showed a high degree of similarity with CCUG 36768. Protein profiling, cellular fatty acid analysis and computer‐assisted analysis of biochemical profiles indicated similarity with Bordetella‐Alcaligenes species, often close to B. holmesii and B. avium. API 20 NE indicated the profile of Moraxella species of poor identity. It is concluded that CCUG 36768 represents a new bacterial species of pathogenic potential in humans. It is related to the Bordetella‐Alcaligenes group. Powerful new methods for speciation are available and it is recommended that unknown isolates from normally sterile sites be submitted for further analysis. Several isolates are required for the definition of new species.
Human cytomegalovirus induces apoptosis in the hematopoietic cell line MO7e
Authors: Sindre Hilde , Rollag Halvor , Olafsen Mette KløVstad , Degre Miklos , Hestdal Kjetil
Published: October 2003

Several studies have shown that human cytomegalovirus (HCMV) induces growth suppression of hematopoietic progenitors. In vitro studies have demonstrated that the HCMV‐induced suppression is independent of viral protein production. Previous studies have indicated a link between HCMV infection and apoptosis in human cells. The purpose of our study was to investigate whether the observed inhibitory effect of HCMV on the human myeloid progenitors could be connected to the induction of apoptosis. The growth and cell death of the hematopoietic cell line MO7e was investigated following infection with HCMV virions and dense bodies. Both virions and dense bodies inhibited the growth of MO7e cells, and induced cell death measured by trypan blue staining. In addition, both HCMV virions and dense bodies caused an increased amount of apoptosis‐characteristic DNA fragmentation in the MO7e cells compared to mock‐treated cells. The HCMV virions were also able to induce an increased expression of phosphatidylserine on the cell surface, which is an early event in the initiation of apoptosis in most cell types. In conclusion, HCMV and HCMV dense bodies are able to induce apoptosis in the myeloid progenitor cell line MO7e
Serum gastrin and gastrin‐immunoreactive cells in the antral mucosa of patients with alcoholic liver disease
Authors: Cortez‐Pinto Helena , Ferra Maria Amelia , Baptista Amelia , De Moura Miguel Carneiro , Portela‐Gomes Guida Maria
Published: October 2003

Backgroundl Aims. Hypergastrinaemia has been reported in liver cirrhosis; meanwhile, it is unclear whether it is associated with an increase in gastrin cell function. The serum gastrin concentration and the number of gastrin cells in antral biopsies were studied in patients with alcoholic liver disease. Methods. Immunocytochemical and quantification techniques were used to localize and determine the number of gastrin cells. Results. Slight non‐significantly higher serum gastrin values were observed in the alcoholic liver disease patients compared with controls, but the individual variation within the groups was considerable. The frequency of gastrin cells did not differ between groups. However, the size of the gastrin cell nuclei was larger in patients with liver disease than in controls, indicating increased cellular activity. Conclusions. Alcoholic liver disease, with a disturbed liver function, influences the gastrin cells. The observed alterations may reflect the effect of alcohol and/or malnutrition, or may be secondary to the influence of liver disease on other regulatory peptides.
Comparison of screening methods for detection of extended‐spectrum β‐lactamases and their prevalence among Escherichia coli and Klebsiella species in Hong Kong
Authors: Ho P. L. , Tsang D. N. C. , Que T. L. , Ho M. , Yuen K. Y.
Published: October 2003

Three tests, the disk diffusion test, the double‐disc synergy test and the inhibitor‐potentiated disc diffusion test, were compared for their abilities to detect production of extended‐spectrum β‐lactamases (ESBL) in 702 Escherichia coli and 472 Klebsiella spp. strains from four hospitals. Eleven percent E. coli and 13%Klebsiella spp. were found to produce ESBL. As an indicator of ESBL activity, the sensitivities of the five extended‐spectrum β‐lactams were as follows: cefotaxime (100%), cefpodoxime (99.3%), ceftriaxone (98.6%), aztreonam (93%) and ceftazidime (57.7%) when interpreted using the National Committee for Clinical Laboratory Standards criteria. Their positive predictive values ranged from 67.8–83.8%. Both the inhibitor‐potentiated disc diffusion test and the double‐disc synergy test (at three inter‐disc widths of 20, 25 and 30 mm) were capable of identifying all the ESBL‐producers. However, at a single inter‐disc width of 30 mm, the double‐disc synergy test has limited sensitivity (83.8%). As a second test for confirming ESBL activity in strains with reduced susceptibility to β‐lactams, the inhibitor‐potentiated disc diffusion test is therefore a simple and reliable option.
Sequence analysis of the hemagglutinin gene of measles virus isolates in Denmark 1997–1998: no evidence of persistent circulation of measles virus in Denmark
Authors: Dahl Lotte , Christensen Laurids Siig , Schöeller Susanne , Westh Henrik , Plesner Anne‐Marie
Published: October 2003

The hemagglutinin‐coding region of 17 virus samples from 12 measles cases in Denmark during 1997–1998 was analysed by partial nucleotide sequencing. The cases appeared as three sporadic cases and two epidemics, both with a limited time course and geographical distribution. The measles strains identified from the three sporadic cases and two epidemics could be allocated to five different previously well‐defined sequence groups consistent with the assumption that cases of measles in Denmark are due to repeated introduction from abroad rather than persistent circulation of strains in the population.
Histopathological evidence of North American blastomycosis in Italy: report of two cases
Authors: Rivasi Francesco , Nanetti Anna , Cesinaro Anna Maria , Mazzoni Aldo
Published: October 2003

No clinical reports of blastomycosis in Italy have been published until now. We here report two cases of histologically diagnosed, unexpected cutaneous involvement in patients, aged 78 and 52 years, living in North Italy and never having been abroad. The histological differential diagnosis between blastomycosis and other fungal pathogens is discussed. Even in the absence of culture the present cases can confidently be considered as genuine examples of Blastomyces dermatitidis infection in Italy.
Vacuolating cytotoxic activity of 40 Helicobacter pylori strains isolated from Turkish patients
Authors: Özsan M. , Tekeli A. , Özden A. , Akyön Y. , Özkul A. , Gerceker D. , Cetinkaya H.
Published: October 2003

In this study we examined the in vitro vacuolating cytotoxic activity of Helicobacter pylori, which is a gram‐negative microaerophilic curved bacterium and a causative agent of gastritis, peptic ulcer and gastric ulcer. A vacuolating cytotoxin assay was performed to assess the vacuolating activity of 40 strains (20 gastritis, 11 gastric ulcer, and 9 duodenal ulcer), which were obtained from patients undergoing upper gastrointestinal endoscopy. The Vero cell line was used in the cytotoxic assay. Of the 40 isolates, 24 (12 gastritis, 6 gastric ulcer, 6 duodenal ulcer) were cytotoxic for the Vero cell line at 1:4 and 1:8 dilutions. Thus, vacuolating cytotoxin of H. pylori affects the Vero cell line, but it seems there is no correlation between the positivity of the strains and the risk of any particular H. pylori disease.
Outbreak of ampicillin‐resistant Enterococcus faecium– risk factors for faecal colonisation
Authors: Mohn S.C , Harthug S. , Langeland N.
Published: October 2003

Since January 1995 there has been a nosocomial outbreak at Haukeland University Hospital involving more than 330 patients with clinical infections caused by ampicillin‐resistant Enterococcus faecium (ARE) (minimum inhibitory concentration ≥32 mg/l). Rectal carriage of ARE was initially observed on two medical wards only. Here the ARE colonisation rate has remained high. To assess risk factors for ARE colonisation we performed a case‐control study including 37 rectal carriers of ARE and 83 non‐carriers on these wards. Significant differences were found between cases and controls with respect to the mean number of days on antimicrobial treatment (13.3 for carriers, 5.5 for non‐carriers, p<0.001), mean number of different antibiotics prescribed (2.8 for carriers, 2.1 for non‐carriers, p=0.008) and mean number of days in hospital (18.4 vs 10.2, p=0.001). Unadjusted statistical analysis showed that several antibiotics were risk factors for ARE carriage. Logistic regression analysis showed that fluoroquinolone prescription (OR=3.5, p=0.01) and more than 10 days of antibiotic use (OR=3.3, p=0.01) were significant risk factors. An additional follow‐up screening of previous carriers revealed no colonisation 8 to 36 (median 9) months after discharge from hospital (n=17). Prolonged antimicrobial therapy and broad‐spectrum antibiotics seem to facilitate nosocomial ARE colonisation.
Expression and activity of matrix metalloproteinase‐2 and ‐9 in experimental granulation tissue
Authors: Inkinen Kaija , Turakainen Hilkka , Wolff Henrik , Ravanti Laura , Kähäri Veli‐Matti , Ahonen Juhani
Published: October 2003

The restoration of functional connective tissue is a major goal of the wound healing process which is probably affected by matrix‐modifying enzymes. To evaluate the spatial and temporal expression of matrix metalloproteinases (MMP) MMP‐2 and MMP‐9 and to study the regulation of MMP‐2 in wound healing, subcutaneously implanted viscose cellulose sponges in rats were used to induce granulation tissue formation for up to 3 months. MMP‐2 mRNA expression was seen throughout the experiment and it was highest after 2 months. MMP‐9 gene expression was low between days 8–21 and increased after 4 weeks of granulation tissue formation. Membrane‐type 1 MMP (MT1‐MMP) mRNA was upregulated early and tissue inhibitor 2 of MMP (TIMP‐2) mRNA later during wound healing. In in situ hybridization the expression of MMP‐2 mRNA was seen mostly in fibroblast‐like cells and MMP‐9 mRNA in macrophage‐like cells. MMP‐9 immunoreactivity was detected in the polymorphonuclear leukocytes and macrophage‐like cells on days 3–8. MMP‐9 proteolytic activity was observed only on days 3–8. The active form of the MMP‐2 increased up to day 14, whereafter it remained at a constant level, whereas latent MMP‐2 did not show any apparent changes during the experimental period. We conclude that MMP‐2 is important during the prolonged remodelling phase, whereas the gelatinolytic activity of MMP‐9 was demonstrated only in early wound healing, and the MMP‐9 gene is upregulated when the granulation tissue matures.
The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type
Authors: Moser Claus , Kjaergaard Susanne , Pressler Tacjana , Kharazmi Arsalan , Koch Christian , Høiby Niels
Published: October 2003

Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection have a persistent acute type lung inflammation dominated by polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P. aeruginosa. We speculated whether this immune response in CF is of the Th2 type and whether a change to a Th1 type immune response could improve the prognosis. Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF –P) chronic P. aeruginosa lung infection. The specific production of interferon‐gamma (IFN‐γ) and interleukin‐4 (IL‐4) by peripheral blood mononuclear cells was determined. Cells from CF +P patients had lower IFN‐γ (p<0.05) and higher IL‐4 (p<0.005) production as compared to cells from CF ‐P patients. Furthermore, a positive correlation between IFN‐γ production and lung function was found (FVC: Rho=0.637; p<0.03; FEV1: Rho=0.524; p<0.07). We conclude that a Th2 type immune response is most frequent in CF patients with chronic P. aeruginosa lung infection, and the patients with a Th1‐dominated immune response had the best lung function. The clinical implication is that a change to a Th1 type immune response might improve the prognosis in these patients.
Enhancement of humoral and protective immune response induced by live‐attenuated Salmonella typhi by ampicillin
Authors: Woo P.C.Y , Tsoi H.W. , Leung H.C.H , Yuen K.Y.
Published: October 2003

Efficacy of live‐attenuated Salmonella vaccines delivered by the mucosal route is limited by the dose and interference from mucosal flora of the alimentary tract. In a mouse model, the total antibody response towards lipopolysaccharide of S. typhi was significantly enhanced at day 21 post‐immunization with live‐attenuated S. typhi (Ty2la) when ampicillin was concomitantly administered (p<0.005), and the lethal dose 50 of mice in the ampicillin and control groups immunized with Ty21a after wild‐type S. typhi challenge on day 24 was 4X107 and 1X107, respectively. The faecal bacterial counts of the ampicillin group at days 1 and 3 were significantly lower than those of the control group (p<0.01 and <0.05). On day 1, the number of mice with ≥10 Ty21a colonies isolated from the spleen was significantly higher in the ampicillin group than the control group (p<0.05). Furthermore, on the same day, Ty21a was isolated from the faeces of three mice from the ampicillin group, but only one from the control group. We conclude that ampicillin may have enhanced the humoral and protective immune responses by giving the Ty21a a selective advantage over the normal bacterial flora. This concept of antibiotic enhancement of immunization could have important implications for other live‐attenuated vaccines, as well as the delivery of microbial antigens and DNA vaccines by live‐attenuated Salmonella carriers.
Detection of vancomycin resistance genes combined with typing of Enterococci by means of multiplex PCR amplification and multiple primer DNA sequencing
Authors: Monstein Hans‐Jürg , Johansson Yvonne , Jonasson Jon
Published: October 2003

A multiplex PCR assay for the detection of vancomycin resistance (van) genes in enterococci was established. Primers targeting the 16S rRNA gene were included in the reaction mixture. Multipleprimer DNA sequencing of the PCR products provided species identification through partial nucleotide sequences of 16S rRNA genes, as well as confirmation of the correct identification of vanA, vanB, vanC‐1, and vanC‐2/3 genotypes. Thirty‐nine enterococcal clinical isolates and type strains were examined for the presence of vancomycin resistance determinants. Twelve other isolates from a clinical reference collection (some of them having vanA, vanB, vanC‐1, or vanC‐2/3 genotypes) were used as controls. Hybridization and partial DNA sequence analysis of multiplex PCR products revealed that none of the clinical isolates had a vanA genotype and only one had a vanB genotype. vanC‐1 was found in three clinical isolates, and vanC‐2/3 in one. Results obtained with the reference and type strains were in agreement with earlier results.
Expression of stanniocalcin in zona glomerulosa and medulla of normal human adrenal glands, and some adrenal tumors and cell lines
Authors: Miura Wakako , Mizunashi Kazutoshi , Kimura Noriko , Koide Yoshio , Noshiro Takao , Miura Yukio , Furukawa Yohtaro , NagurA Hiroshi
Published: October 2003

Stanniocalcin (STC) is a calcium (Ca)‐regulating hormone that was originally discovered in the fish Stannius body, which is a unique endocrine organ. Hypercalcemia increases STC secretion, which inhibits Ca uptake by the gills and normalizes serum Ca level. In this study we investigated the STC expression in human normal and abnormal adrenal cells. Immunohistochemistry using monoclonal antibody against STC revealed specific staining in zona glomerulosa and medulla of normal human adrenal glands. STC was also detected in human adrenal tumors, such as pheochromocytoma, differentiated neuroblastoma, and aldosterone‐producing adenoma, and cultured adrenal tumor cells (rat pheochromocytoma PC‐12 cells and human neuroblastoma NB‐1 cells). However, undifferentiated human adrenal neuroblastoma was negative for STC staining. Reverse transcription polymerase chain reaction demonstrated STC mRNA expression in cultured PC‐12 cells and NB‐1 cells. Following several studies indicating that zona glomerulosa cells of adrenal glands express neuroendocrine properties, STC expression in normal and abnormal adrenal cells provides additional evidence to support the neuroendocrine differentiation of these cells. In conclusion, STC may be useful as a new cell marker of adrenal glands under physiological and pathological conditions.
Interobserver variation in diagnosing coeliac disease, A joint study by Danish and Swedish pathologists
Authors: Weile Birgitte , Hansen Birgit Fischer , Hägerstrand Inga , Hansen Jens Peder Hart , Krasilnikoff P. A.
Published: October 2003

There is an almost 40‐fold difference in incidence rates of symptomatic coeliac disease between Denmark and Sweden. In an attempt to explain this difference, the present study focused on the interobserver agreement when pathologists were assessing small intestinal biopsy specimens from children suspected of suffering from coeliac disease. The study was performed on 90 biopsy specimens from 73 children. Most of the biopsies came from children who turned out not to suffer from coeliac disease after a clinical evaluation including small intestinal biopsy. Using the kappa methodology, the interobserver agreement between two Danish pathologists and one Swedish pathologist, all of whom were experienced, was “moderate” to “substantial” or 0.57–0.75. Kappa indices when the pathologists evaluated selected histological elements were in the interval from 0.24 to 0.67. A comparison of a previous routine diagnostic assessment of the 90 biopsies (14 pathologists) with the results of the experienced pathologists in the present study gave kappa indices of from 0.53 to 0.57. The study could prove no major differences in the histopathological assessment of small intestinal biopsy specimens made by Danish and Swedish pathologists. The difference in clinical presentation of coeliac disease in Denmark and Sweden does not relate to differences in the histopathological assessment of small intestinal biopsies.
Detection and identification of fungi in blood using broad‐range 28S rDNA PCR amplification and species‐specific hybridisation
Authors: Evertsson U. , Monstein H.J , Johansson A.G.
Published: October 2003

The aim of the present study was to develop a PCR‐based method to detect and identify fungi directly from human venous blood. We used broad‐range PCR primers that targeted a part of the large subunit 28S rRNA genes. To obtain species‐specific hybridisation probes, type strains of Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis and Cryptococcus neoformans were PCR amplified, and the amplicons were analysed by gene sequencing. Based on the sequence analysis, species‐specific probes that targeted variable regions were designed and used in hybridisation analyses. Between 2 to 10 fungal cells/ml of spiked blood samples could be detected and correctly identified to species. We applied the technique to blood samples obtained from two patients with or two patients without verified candidaemia. The three samples of candidaemia patients were correctly identified to species level, and those of the negative patients remained negative. This method is a potential tool for diagnosis of systemic invasive candidiasis.
Absence of latent Epstein‐Barr virus in thymic epithelial tumors as demonstrated by Epstein‐Barr‐encoded RNA (EBER) in situ hybridization
Authors: Engel Peter J. H.
Published: October 2003

Background:Several studies have established that Epstein‐Barr virus (EBV) is associated with lymphoproliferative disorders such as Burkitt's lymphoma and Hodgkin's disease. EBV is also present in undifferentiated nasopharyngeal carcinomas and in tumors of similar morphology (lymphoepithelioma‐like carcinomas) arising in a variety of organs, predominantly in stomach, salivary gland and thymus. As reports of EBV‐positive thymic epithelial tumors (TET) have been divergent and as different methods have been used to detect EBV, the aim of this study was to investigate the possible role of EBV in TET of Danish patients.Material and methods:Archival material of 157 cases of TET (105 thymomas and 52 thymic carcinomas, including 4 lymphoepithelioma‐like thymic carcinomas (LELTC)) was analyzed for EBV by applying a sensitive and specific method for detecting latently EBV‐infected cells (in situ hybridization for EBV‐encoded RNA (EBER)).Results:All investigated cases were EBER negative.Conclusions:EBV does not seem to be implicated in the pathogenesis of TET. However, a review of the literature showed that 28% of LELTC were EBER ISH positive. As they occurred in young people (mean 18 years), at an age when the patients were susceptible to infection by EBV, it is suggested that EBV merely acts as an innocent bystander.