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S Spinella

Publications and source records attributed to S Spinella.

At least 19 recordsLinked to original sources
PubMed1998

Expression of the hepatocyte growth factor and c-met in normal thyroid, non-neoplastic, and neoplastic nodules.

We have examined the coexpression of hepatocyte growth factor (HGF) and its receptor (HGF-R or c-met) in an archival series of 63 paraffin-embedded thyroid specimens plus one lymph node metastasis. By immunocytochemistry, we found undetectable expression of both the ligand and the receptor in 10 normal thyroids and 9 nonpapillary malignant nodules [5 follicular carcinomas, 1 poorly differentiated (insular) carcinoma, 3 undifferentiated (anaplastic) carcinomas]. Of 10 non-neoplastic nodules (colloid nodules) and 17 benign neoplastic nodules, 3 of 10 colloid nodules, 2 of 10 follicular adenomas, and 2 of 7 oncocytic adenomas showed a weak but distinct staining (1+ score in a scale from 0 to 4+) of both HGF and c-met in a modest proportion of cells (1% to 3%). In these 7 cases, expression of HGF was always stromal and expression of c-met limited to the membrane of the follicular cells. Of 3 malignant nodules derived from aberrant growth of the parafollicular C cells (medullary thyroid cancer or MTC), 2 were positive (6% of cells). In these 2 cases, the expression of HGF (3+) was not stromal, but in both the membrane and cytoplasm of the parafollicular cells, while that of c-met (3+) was restricted to the membrane. In contrast to all of the above, of 14 papillary carcinomas (PTC) encompassing 5 histological variants (conventional; follicular; oncocytic; with foci of solid growth; diffuse sclerosing) plus 1 neck lymph node metastasis of 1 conventional PTC, 12 (86%) expressed HGF, and 13 (93%) expressed c-met. With the exception of 2 negative cases, HGF was detected in 15% to 46% of the cells. The highest percentage (46%) pertained to conventional PTC cases with abundant peritumoral lymphocyte infiltration, indicating that some lymphokine(s) may recruit PTC cells for HGF expression in a paracrine fashion. With the exception of one negative case, c-met was found in 43% to 80% of the cells, both at levels from intense (3+) to very intense (4+). The immunostaining for HGF was stromal in 25%, membranous in 8%, cytoplasmic in 8%, and both membranous and cytoplasmic in 59% of the PTC-positive cases. The immunostaining for c-met was membranous in 43% and both membranous and cytoplasmic in 57% of the PTC-positive cases. In the lymph node metastasis and in the diffuse sclerosing variant of PTC (the most aggressive variant), the coexpression of HGF/c-met was lost, in that only c-met was expressed on membranes in both cases. We conclude that the HGF/c-met system is activated (by overexpression of both components) in the vast majority of PTC. In most PTC the interaction of HGF and its receptor (c-met) is autocrine, not paracrine.

Carcinoma↗
PubMed1996

Long-term symptom patterns in duodenal ulcer: psychosocial factors.

Seventy-five patients with recent-onset dyspepsia and endoscopically visible duodenal ulcer underwent psychological evaluation. Following ranitidine treatment, they were reinterviewed periodically for 12 to 76 months (mean 38.6). Ulcer symptoms were present during a mean of 14.9% of follow-up months. Patients did significantly worse if they had a low-status occupation, low education, depression, stressful life events, or abnormal Minnesota Multiphasic Personality Inventory at baseline. Of patients recalling premorbid life stress, those with a normal MMPI had a particularly benign course, whereas those with an abnormal MMPI did particularly poorly (6% versus 29% of months symptomatic: p < 0.04). Age, gender, smoking, drinking, antiinflammatory drugs, pepsinogen, Helicobacter pylori titers, and initial healing had no prognostic effect. Low socioeconomic status, life stress, depression, and psychopathology each predict a relatively poor symptom outcome for duodenal ulcer treated with antisecretory therapy, but psychologically stable individuals who develop an ulcer under stress have an excellent long-term prognosis.

Adolescent↗
PubMed1996

Psychologic predictors of duodenal ulcer healing.

We investigated psychologic influences on duodenal ulcer by examining the effect of personality, stress, and mood, measured at diagnosis, on subsequent ulcer healing. Stressful life events, psychopathology (assessed using the Minnesota Multiphasic Personality Inventory), anxiety, depression, smoking, alcohol consumption, nonsteroidal antiinflammatory drug use, and serum pepsinogen I levels were determined immediately after endoscopy showed duodenal ulcer craters in 70 patients with recent onset of symptoms. Endoscopy was repeated following 6 weeks of ranitidine therapy. Six ulcers (8.6%) persisted, and the duodenum remained inflamed in an additional five cases, for a total of 16% with incomplete healing. The only baseline characteristic significantly associated with poor healing was anxiety (p = 0.03 for ulcer persistence, p = 0.02 for incomplete healing). Being in the highest anxiety tertile was associated with a more than fourfold elevation in the risk of incomplete healing (p = 0.02). The association between anxiety and poor healing was not changed by modification of the anxiety score to eliminate gastrointestinal symptom items or by adjustment for serum pepsinogen, sex, or cigarette smoking. Anxiety inhibits the healing of duodenal ulcers treated with adequate antisecretory therapy.

Adolescent↗
PubMed1995

Bile ductopenia following therapy with sulpiride.

We report a case of ductopenia associated with cholestatic hepatitis in a 59-year-old woman treated for 41 years for temporal epilepsy. The patient developed jaundice, without any clinical or biochemical features of hypersensitivity, 10 months after the beginning of treatment with sulpiride. Liver biopsy showed ballooning and acidophilic degeneration of the hepatocytes, macrophages packed with lipofuscin, biliary pigment in Kupffer cells, some biliary plugs, confluent necrosis and absence of biliary ducts in all the portal tracts. These features and the presence of foci of cholangiolitis suggest a destructive cholangitis as the pathogenetic mechanism causing ductopenia. Other causes of ductopenia were excluded. Sulpiride is known to produce severe cholestatic jaundice, which we believe is due to ductopenia. The absence of hypersensitivity and the 10-month latency suggest that sulpiride may cause liver damage through a toxic mechanism in genetically susceptible subjects.

Adult↗
PubMed1995

Hepatitis B E antigen detection in formalin-fixed liver biopsy specimens. A tool to investigate wild-type and E-minus variant HBV infection.

The aim of this study is to investigate whether hepatitis B e antigen (HBeAg) reactivity can be detected on formalin-fixed, paraffin-embedded liver tissue, and whether immunohistochemical detection of intrahepatic HBeAg may help to distinguish between "wild-type" and "eminus" hepatitis B virus (HBV) infection. Liver biopsy specimens were analyzed from 27 patients with chronic type B hepatitis: 12 patients had serum HBeAg (group A), and 15 patients were anti-HBe positive (group B). Part of each biopsy fragment was processed for histologic and immunohistochemical studies, and a part was used for HBV-DNA analysis. Dewaxed sections from each specimen were tested with a specific monoclonal anti-HBe antibody; then a Biotin-Streptavidin kit was used as detection system. HBeAg was revealed in 10 of 12 cases of group A and in 6 of the 15 cases of group B. Pre-core region of HBV genomes, isolated from each biopsy specimen, was analyzed by direct sequencing: 10 cases of group A were found to be infected by wild-type HBV alone and 2 cases by both wild and e-minus HBV types. In group B, all the 6 cases with intrahepatic HBeAg reactivity were found to be infected by mixed viral population, whereas the 9 cases negative for such reactivity were found to be infected by e-minus HBV alone. These results show that HBeAg can be detected in formalin-fixed, paraffin-embedded liver specimens, and the method is sensitive and specific. Because the presence of HBeAg in the liver indicates a wild-type HBV infection, and the lack of detection of such antigen in the hepatocytes of anti-HBe positive subjects correlates with unmixed e-minus HBV infection, the authors conclude that this technique is a useful tool for recognizing the viral strains that infect patients with chronic type B hepatitis.

Adolescent↗
PubMed1995

Patterns of biologic and psychologic risk factors in duodenal ulcer patients.

To clarify whether and how psychologic factors might contribute to peptic ulcer, in this study we addressed the relations between psychologic characteristics and known biologic risk factors among ulcer patients. In 75 patients with recent-onset, symptomatic duodenal ulcer, an index of three potential psychologic risk factors (stressful life events, abnormal Minnesota Multiphasic Personality Inventory, mood disturbance) was examined in relation to historical risk factors (sex, age, seasonality, family history, smoking, alcohol use, coffee consumption, nonsteroidal antiinflammatory drug use), and to blood type, serum pepsinogen I, and Helicobacter pylori antibody titers. The more risk factors in a patient's history, the less likely he or she was to have psychopathology or stress (r = -0.45, p = 0.0007). The mean number of conventional risk factors was 2.7 in patients with all three psychologic risk factors and 4.4 in patients with none; conversely, the mean number of psychologic factors was 0.9 among patients with five or more biologic risk factors and 2.1 among patients with fewer than three risk factors. This negative association was strongest among patients with no previous ulcer history. The psychologic factors also tended to vary inversely with H. pylori antibody titers but not with blood type O or pepsinogen. Duodenal ulcer patients who are atypical in terms of their conventional risk factors are likely to be emotionally fragile, under stress, or both, especially at the time of their first ulcer symptoms. A clinician diagnosing an ulcer in an individual who does not match the usual patient profile should be on the lookout for psychologic factors.

Adolescent↗
PubMed1995

Chronic hepatitis in patients with active hepatitis B virus and hepatitis C virus combined infections: a histological study.

OBJECTIVES: To evaluate whether peculiar histological changes are present in liver tissue of patients with chronic hepatitis by hepatitis B and hepatitis C (HBV and HCV) virus combined infections. METHODS: We studied liver biopsy specimens from 14 HB surface antigen/anti-HCV-positive patients consecutively admitted to hospital because of chronic liver disease from 1987 to 1992. Alcohol abusers, drug addicts, hepatitis delta virus- and HIV-infected subjects were excluded from the study. All of them were positive for serum HBV-DNA and/or intrahepatic HB core antigen and for serum HCV-RNA. Histological examination showed mild or moderate chronic hepatitis in nine cases and severe chronic hepatitis with cirrhosis in five cases. Two additional sets of liver biopsy specimens were also included in the study, consisting of liver samples from 14 patients with chronic liver disease due to active HBV infection alone (group B) and from 14 patients with active HCV infection alone (group C). Cases from group B and C matched for age, sex, and histological diagnosis with those from group B + C. Histological patterns of all the liver specimens of the three groups were re-examined by two authors who scored the found features using a scale from 0 to 3. RESULTS: No peculiar histological pattern was revealed in group B + C, and most of the detected microscopic features were similarly present in all three groups. Bile duct lesions and well defined lymphoid follicles were found only in liver samples of patients from groups C and B + C. Ground-glass hepatocytes were observed only in cases from the groups B and B + C. CONCLUSIONS: Histological examination of liver tissue from patients with chronic HBV and HCV combined infection does not show either typical patterns or evidence that this subgroup of chronic viral hepatitis is a more severe form of liver disease than that caused by a single virus infection. The observation in liver samples of peculiar lesions by HBV or HCV infection does not exclude a combined infection by both viruses.

Adult↗
PubMed1994

5-ASA enema versus oral sulphasalazine in maintaining remission in ulcerative colitis.

This prospective trial in patients with left-sided ulcerative colitis evaluated the efficacy and acceptability of biweekly high-dose 5-aminosalicylic acid (5-ASA) enemas (4g/100ml) in maintaining a remission recently induced using daily 5-ASA enemas. Thirty-one patients were randomly assigned, 16 to 5-ASA and 15 to oral sulphasalazine (2g/day), and examined monthly. Sigmoidoscopy was performed "blind" at six months or at clinical relapse. Twelve patients on 5-ASA (75%) and nine on sulphasalazine (60%) remained in clinical and endoscopic remission throughout the study (NS), and the survival curve for 5-ASA was better at all points (NS). No patient stopped therapy due to side effects, and all those on 5-ASA chose to continue rectal maintenance therapy after the study. It was concluded that biweekly 5-ASA enemas is at least as effective as oral sulphasalazine in maintaining remission in unselected patients whose remission has been achieve using local therapy.

Administration, Oral↗
PubMed1992

Trypanosoma cruzi: predominance of IgG2a in nonspecific humoral response during experimental Chagas' disease.

The kinetic and isotypic pattern of hypergammaglobulinemia has been investigated in C3H/HeJ infected with Trypanosoma cruzi. Hypergammaglobulinemia appeared 14 days postinfection, increased until Day 28 postinfection, and persisted throughout the chronic phase (greater than 60 days of infection). The main isotype secreted was IgG2a, reaching 10-fold the control level. High titers of autoantibodies were found of IgM and IgG subclasses. Isotypic characterization of antibodies against myosin, myelin, and keratin, was performed and determined to be IgG2a subclass in the chronic stage of infection. Specific responses against T. cruzi took place 2 weeks postinfection when the parasitemia was high. Interestingly, parasite-specific response was maximal after 4 weeks of infection and plateaued during the chronic phase when parasites were rare. In contrast to the humoral polyclonal response in the chronic stage, showing a preferential IgG2a pattern, the anti-T. cruzi response consisted of all the different isotypes: IgM, IgG1, IgG3, IgG2a, and IgG2b, throughout the infection. Identical patterns of parasite antigens were recognized by IgG2a and IgG2b antibodies. Few different antigens were identified by the IgG3. Some antigens were recognized by several isotypes, others by only one isotype. With regard to the existence of antigenic cross-reactivities between host and parasite, we designed absorption experiments on parasite-specific immunoadsorbent showing that specific antibodies eluted from the column failed to recognize the natural antigens. These studies suggest that nonspecific and antiparasite-specific responses may be maintained by different regulatory pathways.

Animals↗
PubMed1992

Plasmodium chabaudi and Trypanosoma cruzi infections can reverse IgG2ab chronic suppression in mice.

The effects of infections with Plasmodium chabaudi or Trypanosoma cruzi on chronic CD8+ T cell dependent IgG2ab suppression were analyzed in homozygous Ighb/b adult mice. These parasites are known to induce a CD4+ T cell dependent polyclonal activation characterized in particular by a considerable increase in IgG2a expression. We report here that infection with either parasite reversed the IgG2ab suppression in 18 out of 32 mice. However, in mice treated with anti-CD4 mAb in parallel to the parasite infection, the polyclonal activation was largely reduced and the suppression of IgG2ab expression was always maintained. The parasite induced escape from suppression could result from increased helper T cell activation stimulating some of the Ig production. A weakening of the CD8+ T cell activity which is specific of IgG2ab could also contribute to the IgG2ab production. Both effects would shift the previous equilibrium which was in favour of suppression to a new balance allowing expression of the IgG2ab allotype.

Animals↗
PubMed1992

Life events, personality, and physical risk factors in recent-onset duodenal ulcer. A preliminary study.

To clarify the interactions between stressful life events and other risk factors in the development of duodenal ulcer disease, we studied 33 patients with active ulcer, symptomatic for less than or equal to 6 months and untreated during the previous year, using the Paykel Interview for stressful life events, the Minnesota Multiphasic Personality Inventory (MMPI), and Zung's Anxiety and Depression scales. MMPIs were abnormal in 64% of the patients, and 61% showed some degree of depression. The 16 patients whose symptoms had been preceded by severe stress and more pathological MMPIs, especially on paranoia and dependency scales; were more depressed; and had used less nonsteroidal anti-inflammatory drugs than those without (p less than 0.05). They were somewhat more likely to be single, to be of low social class, and to have recently increased use of cigarettes, alcohol, or coffee (though their absolute level of alcohol consumption was low). Anxiety levels did not differ between stress and nonstress groups. Correspondence analysis yielded four clusters of patients, characterized by (a) alcohol/cigarette use, personality disorder, chronicity; (b) early onset, neurosis; (c) depression, life events; (d) late onset, psychosocial stability. The analysis changed little according to whether life events were or were not considered in cluster formation. We conclude that ulcer patients who become ill under stress from a distinct subgroup, that depressed mood and stress-related increases in use of alcohol and cigarettes may mediate between stress and ulcer formation, and that life events are a quantitatively minor factor in ulcerogenesis.

Adult↗
PubMed1991

Xid immunodeficiency imparts increased parasite clearance and resistance to pathology in experimental Chagas' disease.

Infection of several mouse strains with Trypanosoma cruzi stimulates high levels of T and B lymphocyte activities which persist during the chronic phase and is followed by specific immunosuppression and severe autoimmune pathology. Infected BALB.Xid mice carrying an X-linked mutation and lacking CD5 B cells, display poor B cell responses to T. cruzi infection, accompanied by low levels of specific and non-specific immunoglobulins in the serum. However, these animals control parasitemia, do not show the wasting observed in BALB/c mice, and develop almost no pathology early in the chronic phase. The infection of (BALB.Xid female x BALB/c male) F1 animals shows that immunodefective males behave like Xid animals in contrast to females which respond as normal BALB/c mice. These results indicate that the Xid locus controls lymphocyte responses, parasite clearance and pathology in experimental Chagas' disease.

Animals↗
PubMed1990

A CD4+ TH2 cell line isolated from mice chronically infected with Trypanosoma cruzi induces IgG2 polyclonal response in vivo.

In our study we describe further characteristics of a CD4+ T cell line (G-05) isolated from lymph nodes of C3H/HeJ mice chronically infected with Trypanosoma cruzi. This T cell line secreted lymphokines such as interleukin (IL) 4 and IL 5 and could be defined as a TH2 type of helper T cells. By passive transfer into naive mice, the G-05 line was able to induce a polyclonal B cell activation in the spleen. This splenic B cell activation was quite similar to that seen in chronically T. cruzi-infected animals, where the isotypic pattern presents a large increase of IgG2a and IgG2b isotypes. Moreover, it was possible to reproduce this kind of polyclonal B cell activation in vivo, with the supernatant of G-05 T cells cultured in the presence of T. cruzi extract, accessory cells and exogenous IL 2. Analysis of this supernatant showed the presence of large amounts of IL 4, IL 5, IL 3 and IL 6 but not of interferon-gamma, and residual IL 2 activity was not significant. These results suggest that the G-05 T cells considered as TH2 cells on the basis of their lymphokine production are involved in the development of the in vivo polyclonal B cell activation in T. cruzi infection.

Animals↗
PubMed1989

Anti-Ia treatment modulates specific and polyclonal antibody responses in Trypanosoma cruzi-infected mice.

Experimental Chagas' disease--infection of mice with the protozoan parasite Trypanosoma cruzi--has been shown to increase the number of Ia-bearing cells in the spleen and the lymph nodes. The majority of these Ia-positive cells were Ig+ and included in the large cell fraction of lymphoid organs from T. cruzi-infected animals indicating that they were activated B cells. These data are consistent with the polyclonal B-cell activation occurring during acute and chronic T. cruzi infection. The levels of secreted natural antibodies, of both IgM and IgG isotypes, were significantly increased in the sera of the infected animals. The present communication demonstrates that in vivo anti-Ia treatment of C3H/HeJ mice infected with the CL strain of T. cruzi suppressed the polyclonal B-cell activation, affecting all the isotypes studied, including IgM, IgG2a and IgG2b, whose levels are predominantly increased during T. cruzi infection. In contrast to the decreased secretion of IgG autoantibodies, the levels of IgM autoantibodies were much less affected. The anti-Ia treatment totally abolished the specific anti-parasite response despite the fact that a pool of Ia-Ig positive cells remained after treatment.

Animals↗
PubMed1988

Genetics and strain distribution of concanavalin A-reactive Ly-2-, L3T4- peripheral precursors of autoreactive T cells.

Cytotoxic treatment of BALB/c cells from different peripheral lymphoid tissues by a cocktail of monoclonal antibodies against Thy-1, Ly-1, L3T4 and Ly-2 differentiation markers (anti-T cocktail) plus complement eliminates all mature T lymphocytes. Yet a population of dull Thy-1+, Ly-1-, L3T4-, Ly-2-, corresponding to about 1% of the initial population, can be detected by flow cytometry which proliferate under concanavalin A stimulation. These anti-T killing-resistant cells (TKR) were previously shown to be capable of differentiating in culture into class II-restricted autoreactive T helper cells. We demonstrate here that such cells can be detected in mice of BALB/c and DBA/2 genetic background but are absent in C57BL/6 and B10 animals. The presence of TKR cells is dominant in (BALB/c x C57BL/6)F1 hybrids and genetically controlled by two genes which are neither H-2 nor Igh linked. TKR cells are also detected in young NZB mice but disappear with the development of the systemic autoimmune disease in old animals. Thy-1+, L3T4-, Ly-2- cells from MRL lpr/lpr mice also respond to concanavalin A but are removed by the anti-T treatment. Altogether, arguments are presented suggesting that TKR cells represent a particular subset of double-negative peripheral T cells which may correspond to autoreactive T cell recursors that would escape the thymic selection. We postulate that these cells are present in all mouse strains but their susceptibility to killing by anti-Thy-1 antibodies differs depending on background genes.

Animals↗
PubMed1986

Origin of autoreactive T helper cells. I. Characterization of Thy-1+, Lyt-, L3T4- precursors in the spleen of normal mice.

A new population of dull Thy-1+, Ly-1-, Lyt-2-, L3T4- PNA- cells, resistant to a double cytotoxic treatment by monoclonal antibodies to these T cell markers plus complement, has been isolated from the spleen of normal adult BALB/c and DBA/2 mice (Tkr cells). These cells exhibit no spontaneous autoreactivity or alloreactivity but can be activated with concanavalin A (Con A). Once activated, they differentiate into bright Thy-1+, Ly-1+, Lyt-2-, L3T4+ PNA- T lymphocytes. Con A-activated Tkr cells also strongly proliferate in the presence of allogeneic or syngeneic dendritic cells in secondary cultures. Moreover, contrary to other Con A-stimulated T cell populations, they induce B lymphocytes to proliferate and to differentiate into Ig-secreting cells at a very high level. Con A-activated Tkr cells are therefore very potent polyclonal B cell activators. Restimulated of Tkr cells by syngeneic dendritic cells can be inhibited by anti-L3T4 or anti-class II monoclonal antibodies. The results suggest that Tkr cells are the precursors of class II-specific autoreactive T helper cells. Tkr cells are absent in the spleen of B6 animals. This indicates that their expression might be genetically controlled. It also suggests that Tkr cells may not be the unique splenic precursors of autoreactive T cells. Con A activation of Tkr cells in Click's medium is 2-mercaptoethanol dependent and highly sensitive to pCO2, like the response of thymocytes. Tkr cells are also absent in the spleen of nude mice. We conclude that Tkr cells represent splenic precursors of autoreactive T helper cells equivalent to Thy-1+, Ly-2-, L3T4- PNA- cortical thymocytes.

Animals↗