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Biomedical subjects

B Veress

Publications and source records attributed to B Veress.

At least 19 recordsLinked to original sources
PubMed2006

Combined costimulation blockade prevents rejection of allogeneic islets in mice.

There is a need for immunosuppressive protocols in islet transplantation that are neither nephrotoxic nor diabetogenic. We have examined blockade of the CD28-B7, CD40-CD40L and ICAM-LFA-1 pathways in a model of allogeneic islet transplantation in mice to determine the efficacy of this blockade in prolongation of graft survival. Histological evidences of inflammation and function were evaluated in grafts that had been functioning for 100 days. Treatment with a combination of all three drugs, or with CTLA4Ig and anti-CD40L, administered four times during the first six postoperative days, resulted in an excellent graft survival. All animals had a graft survival of >100 days (i.e. indefinitely). Mice treated with CTLA4Ig and anti-CD40L all showed well-preserved islets without signs of degeneration or destruction. There were no signs of rejection, as evidenced by the absence of infiltrating lymphocytes. This group had the least amount of rejection/inflammation changes according to ranking of all grafts. In conclusion, a short induction treatment with anti-CD40L and CTLA4Ig totally prevents rejection and preserves the allogeneic islets transplanted to mice. The addition of anti-LFA-1 did not confer any benefit.

Abatacept↗
PubMed2005

Differential expression of tissue factor (TF) in calcineurin inhibitor-induced nephrotoxicity and rejection--implications for development of a possible diagnostic marker.

Deposition of fibrin in the form of fibrinoid necrosis is a common feature of severe acute renal allograft rejection. The role of the coagulation system and its initiator tissue factor (TF) during this process is, however, still poorly understood. In this study, we analyzed the expression of TF in 88 renal transplants afflicted with different forms of rejection and calcineurin inhibitor-induced nephrotoxicity, to see whether there was differential expression of this protein. TF immunoreactivity was evaluated semiquantitatively in six different renal structures: the podocytes, Bowman epithelium, the endothelium of the glomeruli, the brush border of tubular cells, the thin ascending loop of Henle, and small arteries/arterioles. The TF expression of normal renal tissue (n=6) was restricted to the glomerular podocytes and Bowman epithelium, and to some extent the ascending loop of Henle. Renal allografts undergoing acute rejection (AR) of grades I-III, (n=13, n=17 and n=12, respectively) did not show any altered TF expression in the glomeruli or vascular endothelium. In the ascending loop of Henle, a reduced expression could be seen (ARI, p=0.015; and ARII, p=0.043). TF staining of the brush border of renal transplants undergoing acute cyclosporin A (CsA) nephrotoxicity (n=18) was significantly higher than in normal kidneys (p=0.0003), as well as in transplants undergoing various degrees of acute rejection (ARI, p=0.027; ARII, p=0.0012; and ARIII, p=0.0001). Tubular brush border-expressed TF was also evident in 10 of 15 allografts suffering from chronic CsA nephrotoxicity, compared to 4 out of 13 cases with chronic allograft vasculopathy (CAV), but the increase was not statistically significant relative to normal kidneys. The majority of the grafts afflicted with either of the two chronic conditions displayed a TF-positive arterial endothelium (CAV, p=0.0034; and chronic CsA nephrotoxicity, p=0.0026) relative to controls. In conclusion, these results indicate that vascular TF expression is not altered during acute rejection, but may be of importance in chronic allograft nephropathy. Furthermore, TF immunoreactivity in the tubular brush border may be specific to acute CsA nephrotoxicity and might be used as a biomarker for this condition. Further studies are required to evaluate the possible role of brush border-expressed TF in the pathogenesis of CsA nephrotoxicity.

Acute Disease↗
PubMed2005

Ki67 and p53 immunohistochemistry reduces interobserver variation in assessment of Barrett's oesophagus.

AIMS: To devise clinically applicable methods for assessing p53 and Ki67 immunohistochemical (IHC) reactivity in Barrett's oesophagus (BE) and to compare the interobserver agreement between these methods and routine haematoxylin and eosin (H&E) evaluation. METHODS AND RESULTS: One hundred and fifteen biopsies diagnosed as BE, selected from the files of the University Hospital MAS, Malmo, were re-evaluated for dysplasia by three pathologists. For IHC analysis areas with the most prominent positivity were evaluated. The mean of p53+ epithelial nuclei/high-power field (HPF) was obtained by counting between 1 and 5 HPFs/biopsy. A proliferation quotient (PQ) was obtained by dividing the number of Ki67+ epithelial nuclei in the upper half by the lower half of the mucosa, using two HPFs. Mean kappa values were 0.24, 0.71 and 0.52 for H&E, p53 and Ki67 evaluations, respectively. There was a correlation between increasing severity of dysplasia, IHC measurable overexpression of p53 and shift of the mucosal proliferation zone towards the surface, measured as PQ. CONCLUSIONS: The described methods for p53 and Ki67 evaluation are more reproducible than routine H&E evaluation of BE. Furthermore, the IHC methods correlate with the severity of dysplasia and are useful supplementary prognostic markers.

Barrett Esophagus↗
PubMed2004

Duodenal intraepithelial lymphocyte-count revisited.

BACKGROUND: The number of intraepithelial lymphocytes in the duodenum was determined 30 years ago, the suggested normal upper limit being 40 lymphocytes per 100 epithelial cells. METHODS: Duodenal mucosa was analysed from 18 healthy individuals and 56 consecutive patients biopsied because of epigastralgia (17 cases), diarrhoea (10 cases), oesophagitis (10 cases), iron-deficiency (9 cases) and B12-deficiency (10 cases) showing normal histology, along with 10 cases of active coeliac disease. The biopsies were fixed in 4% formalin overnight and embedded in paraffin. Three micrometre thick sections were stained with haematoxylin and eosin and CD3. At least 300 epithelial cells were counted, the number of intraepithelial lymphocytes was given as the mean/100 epithelial cells. Extensive statistical analyses were performed. RESULTS: In the healthy individuals the mean number (s) of intraepithelial lymphocytes/100 epithelial cells was 10.8 (2.6) and 13.2 (3.8) in H&E and CD3 stained sections, respectively. The upper limit of the confidence interval for CD3 staining was 29. There was no significant difference between normal individuals and the clinical groups, with the exception of coeliac disease. CONCLUSION: Two-step analysis of intraepithelial lymphocyte-determination is suggested: (a) semi-quantitative estimate on H&E-stained sections (normal ratio of 1:5 between lymphocytes and enterocytes; upper normal limit 20 lymphocytes) and (b) CD3-staining and counting if intraepithelial lymphocytosis is suspected. The upper normal range of intraepithelial lymphocytes is set at 25 CD3+ lymphocytes/100 epithelial cells. Values between 25 and 29 are regarded as 'borderline' and 30 or more represent pathologic intraepithelial lymphocytosis in the duodenum.

Adolescent↗
PubMed2004

Deranged smooth muscle alpha-actin as a biomarker of intestinal pseudo-obstruction: a controlled multinational case series.

BACKGROUND AND AIMS: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a severe motility disorder associated with significant morbidity. Several histopathological (neuropathic and myopathic) phenotypes have been described but only a single adult with jejunal smooth (circular) muscle alpha-actin deficiency. We present a prospective multinational case series investigating smooth muscle alpha-actin deficiency as a biomarker of this disease. METHODS: A total of 115 fully clinically and physiologically (including prolonged (24 hour) ambulatory jejunal manometry) characterised CIIP patients from three European centres were studied. Immunohistochemical localisation of actins and other cytoskeletal proteins were performed on laparoscopic full thickness jejunal biopsies and compared with adult controls. Distribution of alpha-actin was also characterised in other gut regions and in the developing human alimentary tract. RESULTS: Twenty eight of 115 (24%) CIIP patient biopsies had absent (n = 22) or partial (n = 6) jejunal smooth muscle alpha-actin immunostaining in the circular muscle layer. In contrast, smooth muscle alpha-actin staining was preserved in the longitudinal muscle and in adult jejunal controls (n = 20). Comparative study of other adult alimentary tract regions and fetal small intestine, suggested significant spatial and temporal variations in smooth muscle alpha-actin expression. CONCLUSIONS: The ability to modulate alpha-smooth muscle actin expression, evident in development, is maintained in adult life and may be influenced by disease, rendering it a valuable biomarker even in the absence of other structural abnormalities.

Actins↗
PubMed2003

Can contrast-enhanced MR imaging predict survival in breast cancer?

PURPOSE: To investigate the value of pre-operative contrast-enhanced MR imaging (CE-MRI) in predicting the disease-free and overall survival in breast cancer. MATERIAL AND METHODS: The study population consisted of 50 consecutive patients with histopathologically verified primary breast cancer who pre-operatively underwent CE-MRI examination between 1992 and 1993. A three-time point MR examination was performed where the enhancement rates (C1 and C2), signal enhancement ratio (SER=C1/C2) and washout (W=C1-C2) were calculated. The relation of these MR parameters to disease-free and overall survival was investigated. The median follow-up for surviving patients was 95 months. Univariate and multivariate statistical analyses were performed to evaluate the impact of different factors on prediction of survival. RESULTS: Of the MR parameters examined at univariate analysis, increased C1 (p=0.029), W (p=0.0081) and SER values (p=0.0081) were significantly associated with shorter disease-free survival, and only C1 (p=0.016) was related significantly to overall survival. Multivariate analysis for disease-free survival showed that the SER (p=0.014) and tumor size (p=0.001) were significant and independent predictors. Age (p=0.003), lymph node status (p=0.014), tumor size (p=0.039) and proliferating cell nuclear antigen index (p=0.053) remained independently associated with overall survival at multivariate analysis. C1 was not confirmed as an independent predictor of overall survival. CONCLUSION: Our findings support the presumption that CE-MRI is useful in predicting the disease-free survival in patients with breast cancer.

Breast Neoplasms↗
PubMed2002

Flat and depressed colorectal tumours in a southern Swedish population: a prospective chromoendoscopic and histopathological study.

BACKGROUND: Flat and depressed colorectal tumours are common in Japan but are very rare or non-existent in Western countries. AIMS: To study the occurrence of flat colorectal tumours in a southern Swedish population. METHODS: In this prospective study, 371 consecutive European patients were examined by high resolution video colonoscopy combined with chromoendoscopy. The nature of the lesions was determined by histopathological examination. RESULTS: A total of 973 tumours were found; 907 (93.2%) were protruding and 66 (6.8%) were flat or depressed. Of the flat/depressed tumours, five (7.7%) were early adenocarcinomas infiltrating the submucosa. Eleven carcinomas (1.2%) were found among protruding tumours. High grade dysplasia was observed in 18% (n=11) of flat/depressed adenomas in contrast with 7.3% (n=65) of protruding adenomas, and occurred in smaller flat/depressed tumours compared with protruding ones (mean diameter 8 mm v 23 mm, respectively). Furthermore, high grade dysplasia was significantly more common in flat elevated tumours with central depression or in depressed adenomas (35.7%; 5/14) than in flat elevated adenomas (12.8%; 6/47). CONCLUSION: Flat and depressed tumours exist in a Western population. Future studies should address whether or not chromoendoscopy with video colonoscopy is necessary in the search for flat colorectal neoplasms.

Adenoma↗
PubMed2001

Initial inhibition of tissue factor signalling reduces chronic vascular changes in isogenic rat aortic transplants.

Vascular changes are considered the major histopathological indicator of chronic allograft dysfunction. These changes are characterized by intimal thickening caused by accumulation of primarily smooth muscle cells. Contributing factors may be of both immunological and nonimmunological origin. Cold ischemia has been shown to trigger intimal proliferation in the absence of alloantigen in an isogenic rat aortic transplant model. We have used this model to investigate the impact of inhibition of tissue factor (TF) signalling on the progression of intimal thickening. Group 1 was treated with recombinant FVIIa inhibited in its active site (rFVIIai), and group 2 served as untreated controls. At 8 weeks the intimal area was measured with image analysis. Medial areas and the proportion of medial necrosis were determined. Animals treated with rFVIIai showed significantly less intimal thickening compared with controls: median 0.147 vs. 0.256 mm2, respectively (p = 0.008). A positive correlation between intimal hyperplasia and medial necrosis (r(s) = 0.79, p = 0.01), as well as adventitial inflammation (r(s) = 0.83, p = 0.009), was found. TF mRNA was not detected in the neointima at 8 weeks, as determined by in situ hybridization. We conclude that active site inhibited FVIIa (rFVIIai) given prior to and directly after implantation of aortic transplants significantly reduces intimal hyperplasia caused by nonimmunological factors in this model.

Animals↗
PubMed2001

GB virus C/hepatitis G virus infection in patients investigated for chronic liver disease and in the general population in southern Sweden.

Serum samples from patients referred for liver biopsy for investigation of suspected chronic liver disease (n = 286) and from healthy middle-aged volunteers (n = 445) were analyzed for markers of exposure to GB virus C/hepatitis G virus (GBV-C/HGV), hepatitis B virus and hepatitis C virus. GBV-C/HGV analyses included GBV-C/HGV PCR for detection of viremia and GBV-C/HGV enzyme-linked immunosorbent assay for anti-GBV-C/HGV E2 antibodies. Liver biopsies were re-evaluated by a hepatopathologist. GBV-C/HGV markers were detected in 97/286 (34%) patients (GBV-C/HGV RNA = 26; anti-GBV-C/HGV E2 antibodies = 74) compared to 86/445 (19%; p < 0.0001) controls (GBV-C/HGV RNA = 7, anti-GBB-C/HGV E2 antibodies = 79). A significantly higher proportion of GBV-C/HGV-exposed subjects in the patient group were viremic compared to controls (27% vs. 8.1%; p = 0.0015). GBV-C/HGV markers were more commonly found in patients with chronic hepatitis B and C. In patients with GBV-C/HGV viremia, a higher occurrence of bile duct degeneration was detected than in non-viremic patients. Markers of GBV-C/HGV infection were over-represented among patients investigated for chronic liver disease, and ongoing GBV-C/HGV viremia was more common in this group than in controls. Apart from a higher prevalence of bile duct degeneration in viremic patients, infection with GBV-C/HGV did not confer any specific histological characteristics.

Biomarkers↗
PubMed2000

Generalized potential of adult neural stem cells.

The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

Animals↗
PubMed2000

Increased presence of eosinophilic granulocytes expressing transforming growth factor-beta1 in collagenous colitis.

BACKGROUND: Collagenous colitis is a disease characterized by chronic watery diarrhea, and on microscopic examination of colonic tissue, a typical thickening of the subepithelial collagen layer is seen. The etiology and pathophysiology behind this disease state are largely unknown. METHODS: We have used in situ hybridization and immunohistochemistry to study the expression of transforming growth factor (TGF) -beta1, a growth factor with the capacity to cause accumulation of collagen in tissues, in collagenous colitis. Colonic pinch biopsy specimens from a total of 34 patients were investigated: 17 patients with collagenous colitis and 17 controls. RESULTS: In patients with collagenous colitis there was increased expression of the TGF-beta1 gene compared with controls, as visualized by in situ hybridization. The vast majority of the TGF-beta1-expressing cells were eosinophils, both in collagenous colitis and controls, but there were also scattered fibroblastic and histiocytic stromal cells. Immunohistochemistry showed the presence of TGF-beta1, mainly in eosinophils, in the colonic mucosa. Morphometric quantification showed 603 +/- 192 eosinophils/mm2, (mean +/- standard error of the mean) in the colonic mucosa of patients with collagenous colitis compared with 30 +/- 7 eosinophils/mm2 in the controls. CONCLUSIONS: The present results suggest that eosinophils expressing TGF-beta1 may be of pathophysiologic importance in the connective tissue remodeling seen in collagenous colitis.

Adult↗
PubMed2000

Increased presence of cells containing transforming growth factor alpha (TGF-alpha) in ulcerative colitis, both during active inflammation and in remission.

OBJECTIVE: Patients with extensive and long-standing ulcerative colitis have an increased risk of developing colorectal cancer and sub-epithelial fibrosis. The polypeptide transforming growth factor alpha (TGF-alpha) has mitogenic effects and it is believed that local overproduction may result in tumour formation and fibrosis. DESIGN: In the present study, we correlated the presence of TGF-alpha in ulcerative colitis with the degree of inflammation and with dysplasia. METHODS: Sixty two patients were investigated, 46 with ulcerative colitis (16 with active inflammation and 20 in remission, 10 with dysplasia of the colon), and 16 controls with normal colonoscopy and without a history of colitis. There were no overlaps between the subgroups. Tissue sections from colonic biopsies were examined and TGF-alpha was detected by immunohistochemistry. TGF-alpha-containing cells were characterized by double-staining with antibodies to eosinophil cationic protein (ECP). An antibody (EG2) recognizing eosinophils with an activated phenotype was also used. RESULTS: The median number of TGF-alpha-containing cells in the mucosa was 24 per mm2 (inter-quartile range 10-51) in controls, 186 per mm2 (73-245) in ulcerative colitis with active inflammation, 76 per mm2 (52-198) in remission, and 130 per mm2 (66-203) in areas of dysplasia. Double-staining for TGF-alpha and ECP revealed that most of the TGF-alpha-containing cells were eosinophils, and most had an activated phenotype as judged by staining with EG2. CONCLUSIONS: The presence of TGF-alpha-containing cells in colonic mucosa is increased both in active inflammation and during remission in ulcerative colitis. Dysplasia is not associated with any significant increase in TGF-alpha-containing cells. The majority of TGF-alpha-containing cells are eosinophils with an activated phenotype. TGF-alpha released from these cells could be important for the development of complications seen in ulcerative colitis, such as cancer and fibrosis.

Adult↗
PubMed2000

Assessment of liver disease and biochemical and immunological markers in Swedish blood donors with isolated GB virus C/hepatitis G virus viremia.

OBJECTIVE: To investigate signs of liver disease, and biochemical and immunological markers in blood donors with isolated GBV-C/HGV viremia. METHODS: Eighteen donors with isolated GBV-C/HGV viremia were followed up 3-5 years after initial identification. Testing for GBV-C/HGV RNA, GBV-C/HGV-E2 antibodies and a range of biochemical and immunological tests was performed. Thirteen donors consented to liver biopsy. RESULTS: Twelve donors remained GBV-C/HGV viremic at follow-up. Five donors had developed E2 antibodies. Liver biopsies revealed mild portal inflammatory lesions in 6/11 individuals with persistent viremia, and steatosis in 10/13 biopsied donors. CONCLUSION: Steatosis and mild portal inflammatory lesions were found in liver biopsies from several blood donors with isolated GBV-C/HGV viremia.

Adult↗
PubMed1999

Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major.

In this study skin biopsies and peripheral blood samples were obtained from patients with cutaneous leishmaniasis caused by Leishmania major. Samples were obtained at diagnosis and during healing when the lesions had regressed to half the original size. At diagnosis most of the cells expressed HLA-DR. The numbers of CD8+ cells in the lesions were higher at diagnosis than during healing. By contrast, a lower percentage of PBMC expressed CD8+ cells at diagnosis probably due to sequestration in the lesion. In the lesion, in situ staining for IFN-gamma, IL-10, and IL-4 showed marked variation between all patients in the number of positive cells for a particular cytokine. The proliferative response of PBMC to leishmanial antigens and IFN-gamma production tended to increase during healing. Cytokine patterns in the PBMC in response to Leishmania antigen was more specific than in the lesion and correlated better with the clinical manifestations. Possible reasons for this are discussed.

Animals↗
PubMed1999

Interferon gamma (IFN-gamma) deficiency in generalized Epstein-Barr virus infection with interstitial lymphoid and granulomatous pneumonia, focal cerebral lesions, and genital ulcers: remission following IFN-gamma substitution therapy.

A 26-year-old previously healthy woman developed granulomatous pneumonitis, encephalitis, and genital ulceration during primary Epstein-Barr virus (EBV) infection. EBV DNA was demonstrated by polymerase chain reaction analysis of serum, lung tissue, and genital ulcer specimens. Serology verified primary EBV infection. The patient lacked lymphocytes cytotoxic to autologous EBV-transformed B lymphocytes. No spontaneous or in vitro EBV-induced interferon gamma (IFN-gamma) production was evident in peripheral blood. The cells had normal IFN-gamma production when stimulated with Staphylococcus aureus exotoxin A. In the bone marrow and peripheral blood, the number of large granular CD56+ lymphocytes (natural killer cells) increased 39%-55%, but no CD4 or CD8 cell lymphocytosis was initially found. A partial clinical response was achieved with treatment with acyclovir, corticosteroids, and intravenous gamma-globulin. Because of persistent granulomatous central nervous system and lung involvement, subcutaneous IFN-gamma therapy was started but was discontinued after 3 months because of development of fever, pancytopenia, and hepatitis. This therapy initiated a complete clinical recovery, which occurred parallel to development of EBV-specific cytotoxic CD8+ T lymphocytes and normalization of natural killer cell lymphocytosis. These findings provide evidence for an EBV-induced lymphoproliferative disorder due to a T lymphocyte dysfunction associated with a selective lack of IFN-gamma synthesis.

Adult↗
PubMed1998

[Alendronate-induced severe esophagitis. A rare and severe reversible side-effect illustrated by three case reports].

The bisphosphonate, alendronate sodium (e.g. Fosamax), a bone resorption inhibitor used to treat osteoporosis, has occasionally been reported to cause severe oesophagitis. The characteristic endoscopy findings include oesophageal ulceration with discoloured exudate, a narrowed lumen and denuded, haemorrhagic mucosa. The oesophagitis heals on discontinuation of alendronate medication, and the institution of gastric acid suppression treatment. The article consists in discussion of such adverse reactions, illustrated by three case reports. As many of the patients selected for alendronate treatment are elderly and handicapped, to minimise the risk of serious side-effects it is important not only to give detailed instructions regarding medication, but also to ensure that they are properly understood. As a history of swallowing problems was a feature of all three cases reported, caution is recommended before treating such patients with alendronate sodium.

Aged↗