Search PubMed⌕ Search

Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 541 records · Page 30Linked to original sources
PubMed1992

Monoclonal antibody AP-282 recognizes a marker for human polymorphonuclear granules.

Hybridoma AP-282 was produced by fusing mouse plasmacytoma cells with splenocytes of mice immunized against purified human polymorphonuclear cells. The secreted monoclonal antibody (MAb), AP-282, a mouse IgG1, was found to react strongly with all neutrophilic granulocytes, their bone marrow precursors, weakly with blood monocytes and not with eosinophils. The antigen was resistant to formalin fixation but was destroyed by exposure to fixatives containing acetic acid. Using the APAAP technique, antibody AP-282 strongly labelled neutrophils on sections of frozen cut or paraffin embedded tissues. No staining was seen of non hematopoietic tissues. AP-282 recognized an internal antigen associated to cytoplasmic granules. Chemical investigations on dot blots of whole or of purified cellular extracts indicated that the antigen idenfied by MAb AP-282 was different from those recognized by usual antigranulocyte antibodies, i.e. myeloperoxidase, elastase, cathepsin G and lactoferrin. Thus, antibody AP-282 constitutes a new cytoplasmic marker of neutrophils.

Animals↗
PubMed1992

T cells and human autoimmune thyroid disease: emerging data show lack of need to invoke suppressor T cell problems.

Human T cells recognize self and foreign antigens when such antigens are processed into small peptides and bound to molecules coded for by genes of the HLA region on chromosome 6. The part of the T-cell surface which is responsible for such recognition is a set of molecules coded for by a variety of genes and known as the T-cell-receptor complex. In animal models, T cells are able to transfer autoimmune thyroiditis and T cells have, therefore, long been implicated in the etiology of human autoimmune thyroid disease (AITD). Information gained from the study of intrathyroidal T cells and thyroid antigen-specific T-cell clones has shown that in patients with Graves' disease, mainly helper T-cell clones have been obtained, whereas in autoimmune (Hashimoto's) thyroiditis cytolytic T-cell clones may be predominant. Such thyroid antigen-specific T cells have now been shown to recognize one or other of the three major thyroid-specific antigens; thyroglobulin, thyroid peroxidase, or the TSH receptor and efforts are currently in progress to characterize the T-cell epitopes of these major thyroid autoantigens. Recent findings of restricted T-cell receptor V gene use amongst intrathyroidal T cells confirm the primary role of T cells in human thyroid autoimmune processes leading to AITD. However, the mechanisms whereby such autoreactive T cells escape deletion and anergy, and how they become activated, remain uncertain. There is compelling evidence that the thyroid cell itself, by expressing HLA molecules, and presenting antigen directly to the T cells, may initiate disease, perhaps after an external insult.

Amino Acid Sequence↗
PubMed1992

A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

Adult↗
PubMed1992

A phase II trial of continuous infusion cisplatin and 5-fluorouracil with oral calcium leucovorin in colorectal carcinoma.

Twenty previously untreated patients with advanced colorectal adenocarcinoma were entered on a Phase II trial of 3-day continuous infusion cisplatin (25 mg/m2/day) and 5-fluorouracil (800 mg/M2/day) with oral calcium leucovorin (30 mg/dose) every 6 hours. There were four partial responses (20%) and two complete responses (10%) for a total response rate of 30% (95% confidence limits +/- 20%). Patients received a median of 4.5 cycles of therapy (range 2-9 cycles). Three patients experienced neutropenia; one had a life-threatening infection. One developed neuropathy at 375 mg/M2 cumulative dose. Four patients developed mucositis. Treatment was stopped for one patient with stable disease after 5 cycles because of anorexia and nausea and vomiting; treatment was stopped for four patients because of excessive fatigue. The median duration of responses was 4 months (range 3-6 months). Although this regimen is active, the response rate, cumulative nature of the toxicity, and the requirement for hospitalization led us to conclude that this regimen does not warrant Phase III testing but might be a basis for further Phase II therapeutic trials.

Administration, Oral↗
PubMed1992

Characteristics of long-term human thyroid peroxidase autoantibody secretion in scid mice transplanted with lymphocytes from patients with autoimmune thyroiditis.

We have explored scid mice as an in vivo model to study lymphocyte function and autoantibody production in patients with autoimmune thyroiditis and thyroid peroxidase (hTPO) autoantibodies. Patient's peripheral blood mononuclear cells (PBMC) were transplanted into scid mice via intraperitoneal injections and human immunoglobulin G (hIgG) and thyroid autoantibody levels in the murine sera were monitored for a minimum of 3 months after transplantation. Human IgG reached maximum serum levels of > 3,000 micrograms/ml (mean +/- SEM = 1,199 +/- 354 micrograms/ml) after an average of 6.5 weeks. In reconstituted mice (hereafter named At-Scid-hu) substantial titers of anti-hTPO of up to 0.51 (ELISA index, normal range < 0.02) were observed over a period of 1-2 months, followed by a gradual decline. Immunization of AT-Scid-hu mice with immunogenic, recombinant human hTPO (rec-hTPO) failed to enhance hTPO-Ab levels. Furthermore, there was no correlation between the magnitude of human IgG in the murine serum and concomitant levels of anti-hTPO. Murine thyroid function was unaffected by the transplantation of PBMC, as evidenced by normal serum thyroxine (T4) levels, and lack of specific pathologic changes in the thyroid. These data indicate, for the first time, the potential for longer-term human thyroid autoantibody secretion in the scid mouse reconstitution model allowing for further investigation of the regulatory factors inpinging on the human B cells surviving in the murine environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Evidence for selective accumulation of intrathyroidal T lymphocytes in human autoimmune thyroid disease based on T cell receptor V gene usage.

We have investigated the T cell receptor V alpha and V beta gene family usage by T lymphocytes infiltrating affected thyroids in patients with autoimmune thyroid disease. We show that the intrathyroidal T lymphocytes from patients (n = 6) with autoimmune thyroid disease display a widespread usage of V beta gene families with an average of 14.4/19 V beta gene families similar to the peripheral T lymphocytes of the same patients. Because we recently reported that the utilization of V alpha gene families is markedly reduced within these mitogen-stimulated intrathyroidal T cell populations, as well as within intact tissue from similar patients (n = 4) (overall mean of 4.0/18 families detected), these results indicate that in thyroids of patients with autoimmune thyroid disease the lymphocytes are selectively accumulating based on their V alpha rather than V beta elements. This preferential hTcR V alpha and widespread V beta gene usage was not mimicked in most 7-d autologous mixed lymphocyte reactions using non-T cell stimulators (n = 6) or EB-virus immortalized autologous B cell lines (n = 3). Hence, the selective V gene utilization by intrathyroidal T cells is likely to be secondary to multiepitopic thyroidal autoantigens activating thyroid infiltrating T cells or to the presence of a superantigenlike thyroidal self-antigen, capable of determining a selective infiltration or activation of a variety of T lymphocytes on the basis of their V alpha gene usage.

Autoantibodies↗
PubMed1992

Progressive slowing of reaction time and increasing cerebrospinal fluid concentrations of quinolinic acid in HIV-infected individuals.

Neuropsychological functioning and cerebrospinal fluid concentrations of an endogenous neurotoxin, quinolinic acid (QUIN) were evaluated in 52 HIV-positive individuals (71% without constitutional symptoms) and 33 HIV-seronegative controls (including 15 psychiatric patients with adjustment disorders). Although the HIV-positive subjects did not differ from controls on standard neuropsychological tests, simple and choice reactions times (RT) were slow at initial evaluation (P less than 0.01) and became progressively slower at 6-month re-evaluation (P less than 0.05). Cerebrospinal fluid (CSF) QUIN was elevated at initial evaluation and increased during the 6-month interval (P less than 0.05). Moreover, during this 6-month interval, progressive slowing of RT was highly correlated with increasing levels of CSF QUIN (r = 0.85, df = 15, P less than 0.0001) but not with changes in mood, constitutional symptoms, or CD4 cell count. These findings suggest that RT may provide a sensitive behavioral measure of relatively early central nervous system involvement in HIV-infected individuals and that QUIN may play an important role in the pathogenesis of HIV-related neurological dysfunction.

AIDS Dementia Complex↗
PubMed1992

Phosphatidate phosphohydrolases in liver, heart and adipose tissue of the JCR:LA corpulent rat and the lean genotypes: implications for glycerolipid synthesis and signal transduction.

The activities of two distinct phosphatidate phosphohydrolases (PAP) were measured in livers, hearts and adipose tissues of the JCR:LA corpulent rat which is hyperphagic, hypertriglyceridaemic and insulin resistant. The specific activity of PAP-1, which requires Mg2+, was similar in the livers of lean and corpulent female rats and in male corpulent rats, but these activities were about 1.6-fold higher than in lean males. There was a correlation between the specific activity of PAP-1 and the concentrations of hepatic and serum triacylglycerols in the males, but not in the females. Chronic treatment of the corpulent rats with ethanol did not significantly alter the hepatic activity of PAP-1, or the concentrations of hepatic or serum triacylglycerols. Specific activities of PAP-1 in the heart were higher in the lean compared to the corpulent males. There was no significant difference for the females. Specific activities of PAP-1 were over 5-fold higher in the subcutaneous adipose tissue of the corpulent males and females compared to the lean genotypes. The differences were smaller (1.6-1.9-fold) in the gonadal adipose tissue of both sexes and in the peri-renal depot for the males. PAP-1 activity in the peri-renal depots of corpulent females was 23% lower than in lean females. PAP-2 activity was insensitive to N-ethylmaleimide and did not require Mg2+ for activity. Its activity was 1.5-2.0-fold higher in the livers and hearts of the lean male and female rats than in the corpulent genotypes. Chronic treatment with ethanol increased the activity of PAP-2 in the hearts of the corpulent males, but had no effect in the corpulent females. The specific activity of PAP-2 was higher in subcutaneous, gonadal and peri-renal adipose depots in the females and in the peri-renal depot of the corpulent males compared with the lean genotypes. Lean males had higher specific activities in all three depots compared to lean females. The tissue specificity and the sex differences in the specific activities of PAP-1 and PAP-2 are discussed in terms of their proposed functions in glycerolipid biosynthesis and signal transduction. It is proposed that a decreased activity of PAP-2 could be involved in the insulin insensitivity in the corpulent rats.

Adipose Tissue↗
PubMed1992

Antigliadin antibody classes in chronic liver disease.

Antigliadin antibody (AGA) subtypes (IgG and IgA class) were tested in sera from 67 patients with chronic liver disease of different aetiology (29 with primary biliary cirrhosis (PBC), 31 with chronic non-A non-B hepatitis, and 7 with autoimmune chronic active hepatitis (CAH) compared with 23 subjects with inflammatory bowel disease (IBD). Nineteen patients with coeliac disease served as positive controls. IgA-AGA alone were found in 3.4% of patients with primary biliary cirrhosis and in 3.2% of non-A, non-B CAH. IgG-AGA alone were found in 1.3% of patients with IBD, in 6.8% of primary biliary cirrhosis and in 14.2% of autoimmune CAH. IgA-AGA and IgG-AGA together were found in 6.8% of PBC and in 1 patient with autoimmune CAH. Jejunal biopsy, performed in 7 out of the 2 patients with both IgA and IgG-AGA, showed the characteristic features of coeliac disease in one subject with autoimmune CAH. The same patient had the highest titre of AGA. In conclusion, these results indicate that AGA (either IgG and IgA) can be present at low titre in chronic liver disease and their presence may be secondary to the liver damage per sè. High titres of AGA in chronic liver disease may suggest a real association with coeliac disease.

Adult↗
PubMed1992

Production of interleukin-1-like cytokine by cultured rat glomerular macrophages.

Resident glomerular macrophages from normal rats were isolated and grown through long-term cultures in order to obtain confluent cell monolayers. These cells have a secretory function as revealed by the production of a cytokine with a molecular weight similar to interleukin-1 (IL-1). The demonstration that rat glomerular macrophages secrete an IL-1-like cytokine emphasizes the role of these cells in a number of glomerular secretory functions, including some which have been commonly attributed only to mesangial contractile cells.

Animals↗
PubMed1992

Do knowledge and attitudes about influenza and its immunization affect the likelihood of obtaining immunization?

A telephone survey was conducted on 190 patients in Barcelona, Spain, at high-risk for influenza to evaluate the relationship between their knowledge and attitudes toward influenza and influenza immunization and whether they received the immunization. A discriminant function correlates (r = 0.86) with the immunization behavior and predicts the behavior before flu immunization in 84% of cases if we know the previous immunization behavior and adequately classifies the behavior in 82% if we don't know it (r = 0.75). Modifiable factors that predict immunization are self-identification as high-risk, belief that the immunization will not cause discomfort, intention to be immunized, and physician assigned. Those not immunized had a prevalent feeling that the shot is not effective, that they are not susceptible to the illness, and that the health center does not offer satisfactory organization to provide immunization. Furthermore, they felt that they had received controversial information through the mass media. We therefore believe that health education activities regarding influenza immunization should be specifically directed to increasing awareness of those who belong to a high-risk group, as well as to emphasizing susceptibility to the illness and the innocuousness of the immunization.

Aged↗
PubMed1991

Participation of an endogenous inhibitor of fucosyltransferase activities in the developmental regulation of intestinal fucosylation processes.

During the rat weaning period (about day 19 after birth) the intestinal maturation is accompanied by a drastic increase in the fucose content of mucosal glycoconjugates, concomitant with an increase in fucosyltransferase activities. The regulation of this fucosylation process appears to be a rather complex phenomenon, which involves several systems controlling fucosyltransferase activity or substrate availability. An endogenous protein inhibitor of the fucosyltransferase activities displays an opposite developmental pattern to that of fucosyltransferase activities, since its activity is high before weaning and is decreased 5-fold after weaning. Similarly, the GDP-fucose pyrophosphatase activity markedly decreases at weaning. The transformation of GDP-mannose into GDP-fucose increases early, at day 18, preceding the increase in fucosyltransferase activities. Before weaning, and especially at days 14 and 18, high levels of GDP-4-dehydro-6-deoxymannose, the product of the GDP-mannose 4,6-dehydratase activity, are produced during the transformation of GDP-mannose into GDP-fucose, even in excess of reduced coenzyme. This fact indicates that the second step of the transformation (epimerase-reductase reaction) could be a limiting factor for GDP-fucose availability before weaning, but not after weaning. The inverse relationship between the mucosal fucose content (or the fucosyltransferase activity) and the endogenous protein inhibitor during normal postnatal development supports the hypothesis of a physiological role for this inhibitor.

Animals↗
PubMed1991

[Preservation of the bladder in transitional cell tumors infiltrating the lamina propria].

Thirty-two patients with transitional cell cancer of the bladder infiltrating the lamina propria were treated with intravesical BCG. Seventy-five percent of these patients could keep their bladder at the cost of regular BCG treatment and strict endoscopic monitoring. A better evaluation of prognostic criteria, including malignancy grade, total amount of vesical muscle removed during the initial resection and investigation for lymphatic system emboli, should help in a better selection of patients, separating those who might have recurrent infiltrative tumours from those who would benefit from a conservative treatment and offering the former a more aggressive therapy.

Aged↗
PubMed1991

Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease.

BACKGROUND: Patients with autoimmune thyroid diseases, including Graves' disease and Hashimoto's disease, have marked lymphocytic infiltration in their thyroid glands. We examined the gene for the variable regions of the alpha-chain of the human T-cell receptor (the V alpha gene) in intrathyroidal T cells to determine whether the infiltration is a secondary heterogeneous immune response or a more restricted, and therefore primary and presumably pathogenetic, reaction to thyroid autoantigens. METHODS: We used the polymerase chain reaction to detect small numbers of T cells expressing the variable region of the V alpha gene. Different oligonucleotides were used to amplify complementary DNA for the 18 known families of the V alpha gene in intrathyroidal T cells from 9 patients with autoimmune thyroid disease. We compared the findings with the results in patients with nonautoimmune thyroid disease as well as those in normal subjects. RESULTS: We found marked restriction in the expression of T-cell-receptor V alpha genes by T cells from the thyroid tissue of patients with autoimmune thyroid disease. An average of only 5 of the 18 V alpha genes were expressed in such samples, as compared with 17 V alpha genes expressed in peripheral-blood T cells from the same patients. No such restriction was found in thyroid tissue from patients with nonautoimmune thyroid disease. The predominantly expressed V alpha genes differed from patient to patient, however, with no clear association with the type of disease. CONCLUSIONS: Intrathyroidal T-cell accumulation in autoimmune thyroid disease is highly restricted and points to the primacy of T cells in causing thyroid disorders. These results present the possibility of using antibodies to the T-cell receptor for the specific inhibition of abnormal T-cell function in autoimmune thyroid disease.

Antigens, CD↗