Biomedical subjects

E Sabo

Publications and source records attributed to E Sabo.

At least 19 recordsLinked to original sources

PubMed2006

Global analysis of the human gastric epithelial transcriptome altered by Helicobacter pylori eradication in vivo.

OBJECTIVE: The transcriptional profile of gastric epithelial cell lines cocultured with Helicobacter pylori and the global gene expression of whole gastric mucosa has been described previously. We aimed to overcome limitations of previous studies by determining the effects of H pylori eradication on the transcriptome of purified human gastric epithelium using each patient as their own control. DESIGN: Laser capture microdissection (LCM) was used to extract mRNA from paraffin-embedded antral epithelium from 10 patients with peptic ulcer disease, before and after H pylori eradication. mRNA was reverse transcribed and applied on to Affymetrix cDNA microarray chips customised for formalin-fixed tissue. Differentially expressed genes were identified and a subset validated by real-time polymerase chain reaction (PCR). RESULTS: A total of 13 817 transcripts decreased and 9680 increased after H pylori eradication. Applying cut-off criteria (p<0.02, fold-change threshold 2.5) reduced the sample to 98 differentially expressed genes. Genes detected included those previously implicated in H pylori pathophysiology such as interleukin 8, chemokine ligand 3, beta defensin and somatostatin, as well as novel genes such as GDDR (TFIZ1), chemokine receptors 7 and 8, and gastrokine. CONCLUSIONS: LCM of archival specimens has enabled the identification of gastric epithelial genes whose expression is considerably altered after H pylori eradication. This study has confirmed the presence of genes previously implicated in the pathogenesis of H pylori, as well as highlighted novel candidates for further investigation.

Adult↗

PubMed2005

Correlation between levels of tumour necrosis factor-alpha and levels of pH, glucose, and lactate dehydrogenase in parapneumonic effusions.

OBJECTIVES: This study was undertaken to investigate the correlation, which has not been previously investigated, between levels of tumour necrosis factor-alpha (TNF) and levels of pH, glucose, and lactate dehydrogenase (LDH) in pleural fluid of patients with uncomplicated parapneumonic effusion (UCPPE), and patients with complicated parapneumonic effusion (CPPE). METHODS: Using a commercially-available high sensitivity ELISA kit, levels of TNF were measured in pleural fluid of patients with UCPPE (n = 23), and CPPE (n = 15), and were compared with levels of pH, glucose, and LDH in these two groups. RESULTS: The mean +/- SD values of pleural fluid TNF, pH, glucose, and LDH in the UCPPE group were 11.05 +/- 7.65 pg/ml, 7.41 +/- 0.08, 125 +/- 48 mg/dl, and 306 +/- 182 IU/l, respectively. In the CPPE group the values were 56.07 +/- 28.5 pg/ml, 6.82 +/- 0.25, 42 +/- 36 mg/dl, and 2096 +/- 1916 IU/l, respectively. The only significant correlation, which was negative, was found between levels of TNF and pH in the CPPE group (r = -0.62, P = 0.01). Levels of pleural fluid TNF and LDH were significantly higher, and levels of glucose were significantly lower in the CPPE group than in the UCPPE group (P < 0.0001). CONCLUSIONS: This study demonstrates, for the first time that TNF levels correlate inversely with levels of pH in pleural fluid of patients with CPPE but not of patients with UCPPE. This correlation may, in part, explain the pathophysiology of the pleural complications which occur in the presence of CPPE.

Adult↗

PubMed2005

Increased plasma levels of matrix metalloproteinase-9 are associated with the severity of chronic urticaria.

BACKGROUND: Matrix metalloproteinase (MMP)-9 is produced by many inflammatory cells such as macrophages, neutrophils, mast cells, eosinophils and T lymphocytes. Activated T cells are capable, through cell-cell contact, of inducing MMP-9 expression in human mast cells. OBJECTIVE: To investigate the activation status of peripheral CD4+ T cells and the level of MMP-9 in the plasma of patients with chronic urticaria (CU), and whether MMP-9 levels are in association with CU severity. METHODS: Study subjects included 29 patients with CU and 30 healthy control subjects. At the time of assessment, patients were divided into subgroups according to urticarial severity. Plasma levels of total MMP-9 (free pro-MMP-9 and free MMP-9) were determined by ELISA. CD4+ lymphocytes were positively selected with magnetic microbeads. After 48 h of activation, CD4+ T cells were assayed for both nuclear factor-kappa B (NF-kappa B) expression and proliferation. RESULTS: Plasma levels of MMP-9 were found to be significantly higher in 29 CU patients compared with 18 healthy controls (186 +/- 174 vs. 31 +/- 21 ng/mL, P<0.0001). We also found a significant correlation between MMP-9 levels and urticarial severity (r = 0.92, P<0.001). In addition, CD4+ T cells from CU patients expressed higher levels of NF-kappa B than CD4+ T cells from healthy controls (82 +/- 30 vs. 69 +/- 20 optical density, P = 0.007). Finally, as compared with seven healthy individuals, DNA synthesis in CD4+ T cells from seven CU patients was found to be significantly elevated (1000 +/- 240 vs. 751 +/- 166 counts per minute, P = 0.01). CONCLUSION: Increased levels of MMP-9 are found in CU patients, and particularly among those with severe disease. We also demonstrated that CD4+ T cells from such patients are highly activated.

Adolescent↗

PubMed2004

Decreased level of the cell cycle regulator p27 and increased level of its ubiquitin ligase Skp2 in endometrial carcinoma but not in normal secretory or in hyperstimulated endometrium.

p27 is a cyclin-dependent kinase (CDK) inhibitor whose specific late G(1) destruction allows progression of the cell across the G(1)/S boundary. The protein is ubiquitinated by S-phase kinase-interacting protein-2 (Skp2) following its specific phosphorylation, and is subsequently degraded by the 26s proteasome. There is a direct relationship between low level of p27 and rapid proliferation occurring in several benign states and in many malignancies. In the glandular cells of the normal endometrium, the level of p27 is exceedingly low during the proliferative phase, whereas it is markedly increased during the secretory phase. The expression of p27 in endometrial carcinoma is very low but has been found to increase following treatment with progesterone. However, estrogen exposure is considered as a major risk factor in developing endometrial cancer. The implications of the high dose of estrogen and progesterone induced during IVF treatment are still unknown. We have examined the expression of p27 and Skp2 as well as of Ki67 proliferation marker by using endometrial extracts and cells from normal endometrium, from ovarian hyperstimulated patients, and from endometrial carcinoma patients. The expression of p27, Skp2 and Ki67 was found to be similar in both normal secretory endometrium and endometrium from ovarian hyperstimulated patients. In striking contrast, p27 is significantly lower while Skp2 and Ki67 are significantly higher in the endometrial carcinoma and in endometrium from the proliferative phase compared with their normal secretory counterpart tissue.

Biopsy↗

PubMed2004

Patterns of cardiovascular reactivity in disease diagnosis.

BACKGROUND: Aberrations of cardiovascular reactivity (CVR), an expression of autonomic function, occur in a number of clinical conditions, but lack specificity for a particular disorder. Recently, a CVR pattern particular to chronic fatigue syndrome was observed. AIM: To assess whether specific CVR patterns can be described for other clinical conditions. METHODS: Six groups of patients, matched for age and gender, were evaluated with a shortened head-up tilt test: patients with chronic fatigue syndrome (CFS) (n = 20), non-CFS fatigue (F) (n = 15), neurally-mediated syncope (SY) (n = 21), familial Mediterranean fever (FMF) (n = 17), psoriatic arthritis (PSOR) (n = 19) and healthy subjects (H) (n = 20). A 10-min supine phase was followed by recording 600 cardiac cycles on tilt (5-10 min). Beat-to-beat heart rate (HR) and pulse transit time (PTT) were measured. Results were analysed using conventional statistics, recurrence plot analysis and fractal analysis. RESULTS: Multivariate analysis evaluated independent predictors of the CVR in each patient group vs. all other groups. Based on these predictors, equations were determined for a linear discriminant score (DS) for each group. The best sensitivities and specificities of the DS, consistent with disease-related phenotypes of CVR, were noted in the following groups: CFS, 90.0% and 60%; SY, 93.3% and 62.5%; FMF, 90.1% and 75.4%, respectively. DISCUSSION: Pathological disturbances may alter cardiovascular reactivity. Our data support the existence of disease-related CVR phenotypes, with implications for pathogenesis and differential diagnosis.

Adult↗

PubMed2004

Clinical and laboratory parameters in predicting chronic urticaria duration: a prospective study of 139 patients.

BACKGROUND: Despite the disabling nature of chronic urticaria (CU), little is known about the disease's duration or the efficacy of adopting aggressive therapeutic regimens such as cyclosporine A. OBJECTIVES: The aim of this study was to evaluate whether parameters such as angioedema, autologous serum test, anti-thyroid antibodies, and total IgE could predict both CU duration and severity. PATIENTS AND METHODS: One hundred and thirty-nine patients suffering from CU were prospectively followed over a 5-year period for disease duration, severity and the presence of angioedema. Also investigated was the association between these clinical parameters and the subsequent detection of autologous serum test, anti-thyroid antibodies, and total IgE. RESULTS: CU lasted over 1 year in more than 70% of cases and in 14% it still existed after 5 years. Angioedema co-existed or appeared during the course of CU in 40% of patients and was associated with disease duration. Autologous serum test and anti-thyroid antibodies were found positive in 28 and 12% of patients, respectively, compared to none of normal individuals, P = 0.001. CU duration was associated with the presence of both autologous serum test and anti-thyroid antibodies; however, autologous serum test and not anti-thyroid antibodies was found in association with CU severity. CONCLUSION: We demonstrate for the first time that CU duration is associated with clinical parameters such as severity and angioedema, and with laboratory parameters such as autologous serum test and anti-thyroid antibodies. The ability to predict CU duration may facilitate decisions regarding the possible early initiation of cyclosporine A as a means by which to reduce disease severity and duration.

Adolescent↗

PubMed2004

Serum levels of tumor necrosis factor-alpha correlate with severity of hepatic encephalopathy due to chronic liver failure.

BACKGROUND: Several studies have shown that serum levels of tumor necrosis factor-alpha (TNF) are significantly elevated in patients with acute and chronic liver diseases, where these elevations are independent of the etiology of the underlying disease. Serum levels of TNF are significantly higher in patients with cirrhosis than in those without cirrhosis, reaching the highest levels in decompensated cirrhosis. It has also been shown that plasma levels of TNF correlate with the severity of hepatic encephalopathy (HE) in fulminant hepatic failure. However, still there are no published data regarding the relationship between blood levels of TNF and the presence or severity of HE in patients with chronic liver failure. AIM: The aim of this study is to determine the relationship between serum levels of TNF and clinical grades of HE in patients with liver cirrhosis. METHODS: Using a commercially available high-sensitivity enzyme-linked immunosorbent assay kit, serum levels of TNF were measured in 74 patients with liver cirrhosis in various clinical grades of HE (grades 0-4). RESULTS: The mean+/-SEM values of serum levels of TNF at presentation in patients with grade 0 of HE (n=23), grade 1 (n=12), grade 2 (n=14), grade 3 (n=16), and grade 4 (n=9) were 4.50+/-0.46, 9.10+/-1.0, 12.98+/-1.22, 21.51+/-2.63, and 58.26+/-19.7 pg/ml, respectively. A significant positive correlation was found between serum levels of TNF and the severity of HE (P<0.0001). CONCLUSION: Serum levels of TNF correlate positively with the severity of HE in patients with chronic liver failure.

Aged↗

PubMed2003

Assessment of cardiovascular reactivity by fractal and recurrence quantification analysis of heart rate and pulse transit time.

Methods used for the assessment of cardiovascular reactivity are flawed by nonlinear dynamics of the cardiovascular responses to stimuli. In an attempt to address this issue, we utilized a short postural challenge, recorded beat-to-beat heart rate (HR) and pulse transit time (PTT), assessed the data by fractal and recurrence quantification analysis, and processed the obtained variables by multivariate statistics. A 10-min supine phase of the head-up tilt test was followed by recording 600 cardiac cycles on tilt, that is, 5-10 min. Three groups of patients were studied, each including 20 subjects matched for age and gender--healthy subjects, patients with essential hypertension (HT), and patients with chronic fatigue syndrome (CFS). The latter group was studied on account of the well-known dysautonomia of CFS patients, which served as contrast against the cardiovascular reactivity of the healthy population. A total of 52 variables of the HR and PTT were determined in each subject. The multivariate model identified the best predictors for the assessment of reactivity of healthy subjects vs CFS. Based on these predictors, the "Fractal & Recurrence Analysis-based Score" (FRAS) was calculated: FRAS=76.2+0.04*HR-supine-DET -12.9*HR-tilt-R/L -0.31*HR-tilt-s.d. -19.27*PTT-tilt-R/L -9.42*PTT-tilt-WAVE. The median values and IQR of FRAS in the groups were: healthy=-1.85 (IQR 1.89), hypertensives=+0.52 (IQR 5.78), and CFS=-24.2 (5.34) (HT vs healthy subjects: P=0.0036; HT vs CFS: P<0.0001). Since the FRAS differed significantly between the three groups, it appears likely that the FRAS may recognize phenotypes of cardiovascular reactivity.

Adult↗

PubMed2003

The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome.

BACKGROUND: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a 'haemodynamic instability score' (HIS). AIM: To assess HIS sensitivity and specificity in the diagnosis of CFS. DESIGN: Prospective controlled study. METHODS: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT. RESULTS: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%. DISCUSSION: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician's diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.

Adult↗

PubMed2003

Quinacrine added to ongoing therapeutic regimens attenuates anticardiolipin antibody production in SLE.

The benefit of combining quinacrine (Qn) with hydroxychloroquine (HCQ) in the treatment of systemic lupus erythematosus (SLE) was previously re-evaluated by us. In our current study we observed that, in 11 active SLE patients (SLEDAI score 5-12), the addition of Qn (100 mg/day) to their existing ongoing therapeutic regimens resulted in a significant attenuation of their previously persistent anticardiolipin antibody (aCL) response. This was in comparison with a matched non-Qn treated control group composed of 14 randomly chosen aCL-positive SLE patients with a similar SLEDAI score 6-10. Prior to Qn treatment the therapeutic regimens of 12 months' duration, included in all cases HCQ (400 mg/day), in many cases prednisone (P, 10-20 mg/day) and in some additional cases immunosuppressive drugs. SLEDAI scores and aCL levels were monitored during the entire follow-up period which totaled 24 months in the study group and 15-18 months in the controls. Along with the beneficial effect of the added Qn on SLEDAI scores, aCL disappearance was documented in eight of 11 patients and remained negative during 8-12 months of follow-up (P = 0.004), compared with such a change in only three of 14 non-Qn treated aCL-positive patients (P = 0.18). We conclude that the added Qn treatment to former established therapeutic protocols may eliminate aCL response in SLE patients. Whether this agent's effect is permanent needs further elucidation.

Adult↗

PubMed2002

Lipopolysaccharide endotoxemia reduces cell proliferation and decreases enterocyte apopotosis during intestinal adaptation in a rat model of short-bowel syndrome.

Sepsis is frequently associated with or complicates short-bowel syndrome (SBS). To investigate the effects of lipopolysaccharide (LPS) endotoxemia on enterocyte proliferation and death via apoptosis in a rat model of SBS, adult male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis; SBS rats underwent 75% small-bowel resection; and SBS-LPS rats underwent 75% bowel resection and were given intraperitoneal injections of LPS 10 mg/kg. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth), enterocyte proliferation, and death via apoptosis were determined on day 15 after the operation. Statistical analysis was determined by Student's and ANOVA tests with a P less than 0.05 considered significant. SBS-LPS animals demonstrated a significant decrease (vs SBS rats) in duodenal (20%), jejunal (30%), and ileal (15%) overall weight, duodenal (20%), jejunal (27%), and ileal (18%) mucosal weight, jejunal (20%) and ileal (30%) mucosal DNA, jejunal (29%) and ileal (31%) villus height, and jejunal (14%) and ileal (29%) crypt depth. LPS endotoxemia led to reduced cell proliferation and enterocyte apoptosis compared to untreated SBS animals. Thus, in a rat model of SBS, LPS endotoxemia inhibits intestinal adaptation. A possible mechanism may be decreased cell proliferation. Decreased enterocyte loss via apoptosis may reflect a reduced number of enterocytes. Other mechanisms (necrosis) may be mainly responsible for cell death following LPS injection.

Adaptation, Physiological↗

PubMed2002

Correlation between polymorphonuclear leukocyte counts and levels of tumor necrosis factor-a in pleural fluid of patients with parapneumonic effusion.

High concentrations of tumor necrosis factor-a (TNF), as well as excess of polymorphonuclear leukocytes (PMNs), are present in pleural fluid of patients with complicated parapneumonic effusion (CPPE). Several studies have shown that PMNs are capable of secreting TNF. However, the correlation between levels of TNF and PMN counts in pleural fluid of patients with parapneumonic effusion has not been previously evaluated. This study was undertaken to evaluate this correlation. Using a commercially available high sensitivity ELISA kit, levels of TNF were measured in pleural fluid of patients with UCPPE (n = 22), and CPPE (n = 14), and were compared with PMN count in pleural fluid of these patients. The mean +/- SD values of pleural fluid TNF and PMN count in the UCPPE group the group were 10.15 +/- 6.48 pg/mL and 3,452 +/- 2,878 cells/mm3, respectively, and in the CPPE group the values were 55.51 +/- 29.49 pg/mL and 25,261 +/- 11,733 cells/mm3, respectively. Levels of pleural fluid TNF and PMN counts in the CPPE group were significantly higher than in the UCPPE group (p <0.0001). A significant correlation was found between levels of pleural fluid TNF and PMN counts in the CPPE group (r = 0.57, p = 0.03) and also in the UCPPE group (r = 0.44, p = 0.04). The results of this study indicate that in pleural fluid of patients with UCPPE or CPPE, levels of TNF correlate positively with PMN counts, and PMNs might be an important source of TNF production in pleural fluid of these patients, particularly in those with CPPE.

Adult↗

PubMed2002

Second trimester abortion by laminaria followed by vaginal misoprostol or intrauterine prostaglandin F2alpha: a randomized trial.

Intra-amniotic injection, as well as intravaginal application of prostaglandins, have been used to terminate second trimester pregnancies. There is as yet no consensus as to the most efficient protocol of such late abortions. Our goal was to compare the efficacy of intra-amniotic injection of prostaglandin F2 alpha (PGF2alpha) and intravaginal application of misoprostol in terminating second trimester pregnancies after pretreatment with intracervical laminaria. Women with live fetuses and requesting second trimester abortions were randomized into two groups. Eighteen hours following the insertion of intracervical laminaria, women were treated with either intra-amniotic injection of 40 mg PGF2alpha, or 12 hourly doses (to a maximum of 4 doses) of 200 mcg misoprostol. Fifty women were randomly assigned to each group. Failure to abort within 24 h of initiation of treatment occurred in 6 patients (12%) in the misoprostol group and 14 (28%) of the PGF2alpha group (p = 0.04). Mean time of induction of pharmacologic treatment to abortion was 13.6 h in the misoprostol group and 10.7 h in the PGF2alpha group (p = 0.03). The mean number of analgesic injections given were 0.8 in the misoprostol group and 1.6 in the PGF2alpha group (p = 0.0001). Only the method of abortion was predictive of abortion success and not other variables such as patient age, gestational age, gravidity, or parity. Following intracervical laminaria, vaginal misoprostol has been found to be more effective and less painful, compared with intra-amniotic PGF2alpha, for the termination of second trimester pregnancies with live fetuses.

Abortifacient Agents, Nonsteroidal↗

PubMed2002

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation evolving to an overt lymphoma. Recently, CD81 was identified as an HCV receptor on B-lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. In addition, expansion of CD5+ B lymphocytes was described to be associated with various non-HCV related autoimmune disorders. Therefore, we studied the possible role of peripheral B cells CD81 and CD5 over-expression in the development of HCV-related autoimmunity and their association with disease severity in chronic HCV infection. Peripheral B cells CD5 expression and mean fluorescence intensity (MFI) of CD81 were determined in 30 HCV-infected patients, 30 healthy controls and 15 patients with hepatitis B virus infection using fluorescence-activated cell scan (FACS). We have also investigated the association between peripheral CD5 and CD81 B-cell over-expression and markers of autoimmunity and disease severity in patients chronically infected by HCV. CD5+ B-cells were increased in chronic HCV infection (23.2 +/- 7.2%) compared with those of healthy controls (15 +/- 5.5%) (P < 0.0001) and chronic HBV infection (19 +/- 3.7%) (P = 0.08). CD81 MFI was significantly higher in HCV-infected compared to HBV-infected patients and healthy controls. Both increased CD81 MFI and CD5+ B-cell expansion were associated with the production of rheumatoid factor and mixed cryoglobulins and positively correlated with HCV viral load and histological activity index. The overexpression of CD81 and the expansion of CD5+ peripheral B-cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.

Adult↗

PubMed2002

Ki67 antigen and PCNA proliferation markers predict survival in anorectal malignant melanoma.

AIMS: To find a possible correlation of Ki67 antigen and proliferating cell nuclear antigen (PCNA) with prognosis in anorectal malignant melanoma. METHODS AND RESULTS: Thirty patients with anorectal malignant melanoma were studied. The percentage of tumour cells stained for Ki67 and PCNA in paraffin sections was assessed. Mode of treatment (local excision or abdominoperineal resection), depth of tumour invasion, attempt at cure as defined by complete tumour excision and absence of distant metastases at presentation, tumour blood vessel invasion, and tumour necrosis, as well as Ki67 and PCNA, were all correlated with survival. By univariate analysis, PCNA, Ki67, attempt at cure, local excision (and not abdominoperineal resection), and depth of invasion were all significantly associated with longer survival. By multivariate analysis, only PCNA was significantly associated with survival, while Ki67 showed a significant positive correlation with PCNA. With a cut-off point of 40%, patients with lower Ki67 scores showed survival advantage over those with higher Ki67 scores (P=0.0004). With a cut-off point of 80%, patients with lower PCNA scores showed survival advantage over those with higher PCNA scores (P=0.0001). The staining for proliferation markers was also associated with depth of tumour invasion. CONCLUSIONS: Ki67 and PCNA immunostaining in paraffin sections may be useful for the prediction of survival in patients with anorectal malignant melanoma. Larger studies are needed to confirm our results.

Aged↗

PubMed2002

Cytotoxic phenotype of intra-epithelial lymphocytes in normal and cryptorchid human testicular excurrent ducts.

BACKGROUND: Most testicular and epididymal lymphocytes express T-cell markers, but their cytotoxic potential and activation status have not been reported. In this study, distribution of the cytotoxic cells was compared between normal and cryptorchid testes stratified into two groups: the first with complete absence of germ cells [Sertoli cell-only (SCO)] and the second with arrested spermatogenesis (SCA). METHODS: Immunohistochemistry for the T-lymphocyte marker CD3 and cytotoxic markers CD8, TIA-1 and granzyme B was performed on paraffin-embedded sections. RESULTS: The number of CD8+ and CD3+ intra-epithelial lymphocytes (IELs) increased distally throughout the normal epididymis. TIA-1 immunostaining revealed that a significant proportion of IELs exhibited cytotoxic potential, whereas granzyme B staining disclosed a subpopulation of activated cytotoxic lymphocytes (CTLs). TIA-1/CD8 and granzyme B/CD8 double immunostaining revealed that the vast majority of TIA-1+ and granzyme B+ cells were CD8+. The proportion of activated granzyme B+ lymphocytes increased distally throughout the normal epididymis. The number of TIA-1+ and granzyme B+ intra-epithelial and stromal lymphocytes was significantly increased in the normal as opposed to the SCO cryptorchid epididymis and proximal vas deferens. CONCLUSIONS: These results suggest that exposure of the testicular excurrent ducts to spermatozoa or immature germ cells triggers the activation and recruitment of CTLs. Cytotoxic granule effector mechanisms may contribute to the immunological barrier preventing the immune response to spermatozoa in testicular ducts.

Adolescent↗

PubMed2001

Neuroendocrine cells along the digestive tract express neuropilin-2.

Neuropilin-2 (np-2) is a receptor for semaphorin-3F (sema-3F) and semaphorin-3C (sema-3C). These semaphorins repel tips of growing axons that express np-2. In addition, np-2 functions as a receptor for heparin binding forms of the angiogenic factor vascular endothelial growth factor (VEGF) such as VEGF145 and VEGF165. We report that np-2 is strongly expressed in neuroendocrine cells located all along the human digestive tract. Confocal fluorescent microscopy revealed that np-2 is concentrated in vesicle-like structures located near the nucleus at the basolateral side of these cells. In the colon, the np-2-expressing subpopulation of neuroendocrine cell is almost identical with the serotonin-producing subpopulation of neuroendocrine cells. Gastrointestinal carcinoid tumors are digestive tract tumors that develop from neuroendocrine cells. Interestingly, most of the carcinoid tumors derived from the colon and the appendix did not contain np-2-producing cells. However, some carcinoid tumors derived from the small intestine and stomach did express low levels of np-2 in isolated foci of cells. By contrast, strong serotonin and chromogranin-A expression was observed in all of the carcinoid tumors that were examined. These results suggest that loss of np-2 expression may accompany tumor progression in carcinoid tumors.

Carcinoid Tumor↗

PubMed2001

The effect of antiviral therapy on t(14;18) translocation and immunoglobulin gene rearrangement in patients with chronic hepatitis C virus infection.

The mechanism of lymphomagenesis of hepatitis C virus (HCV)-related B-cell lymphoma is unknown. Recently, it has been suggested that HCV may induce B-cell clonal proliferation and t(14;18) translocation in patients chronically infected with the virus. Thus, this study investigated the effect of antiviral treatment on immunoglobulin heavy-chain gene (IgH) rearrangement and t(14;18) translocation in HCV infected patients. Twenty-nine patients with chronic HCV infection were studied in whom IgH rearrangement and/or t(14;18) translocation were previously detected. The IgH rearrangement (FR3/JH) and t(14;18) translocation (MBR bcl2-JH) were detected in peripheral blood mononuclear cells by polymerase chain reaction. Fifteen of 29 patients (8 with IgH rearrangement, 6 with t(14;18) translocation, and 1 with both) were treated with either interferon-alpha or by combination therapy with interferon and ribavirin for 6 to 12 months. IgH rearrangement became negative in 7 of 9 treated patients compared with only 1 of 8 of nontreated patients (P <.02). The t(14;18) translocation became negative in 6 of 7 treated patients compared with 1 of 6 nontreated patients (P =.03). Disappearance of IgH rearrangement or t(14;18) translocation was strongly associated with virologic response to treatment. Two t(14;18)+ patients developed B-cell lymphoma during follow-up. Antiviral treatment appears to be effective in eliminating the clonal proliferation of B cells in patients with chronic HCV infection and may prevent the subsequent development of lymphoma. The mechanism can be related to a direct effect of interferon-alpha on the proliferating clone or to an indirect effect by eradicating the antigenic stimulus.

Adult↗