Search PubMed⌕ Search

Biomedical subjects

M Lombard

Publications and source records attributed to M Lombard.

At least 73 records · Page 4Linked to original sources
PubMed1991

High serum levels of CD8 antigen in primary biliary cirrhosis: a possible cause of suppressor cell dysfunction?

Reduced suppressor cell number and function have been described in a number of autoimmune diseases and this may contribute to pathogenesis. Suppressor cell function depends upon the interaction of the CD8 antigen expressed on suppressor cells with other limbs of the immune system. Recently, soluble membrane antigens including CD8 have been identified in serum and it is possible that the loss of such antigens from viable cells could result in functional deficit. In order to examine whether the decreased suppressor cell function reported in autoimmune type of chronic liver disease is associated with soluble serum CD8 levels, sera from 23 patients with primary biliary cirrhosis (PBC), 12 with autoimmune chronic active hepatitis (AI-CAH) and 21 healthy controls were tested using a commercially available enzyme immunoassay. The proportion of cells expressing the CD8 antigen and the intensity of its display were also determined using an immunofluorescent technique and an ELISA, respectively, for 12 PBC and 10 healthy controls. The soluble serum CD8 levels were significantly higher in PBC (mean U/ml +/- s.d., 777 +/- 331), and AI-CAH (575 +/- 291) than controls (322 +/- 115) (P less than 0.001 and P = 0.004, respectively). While the intensity of CD8 antigen expression on suppressor/cytotoxic populations was not significantly different in PBC (347 +/- 125 per 10(4) cells) compared with controls (441 +/- 206), the mean proportion of CD8 positive cells was significantly less in PBC (14.1 +/- 6.8%) than controls (20 +/- 4.7%) (P less than 0.05). These data suggest that the apparent reduction in suppressor cell number found for patients with PBC and AI-CAH may be a consequence of the shedding or secretion of CD8 antigen from cell membrane of CD8 positive lymphocyte. It is also possible that the loss of this antigen is responsible for the reduced suppressor cell function seen in these conditions.

Adult↗
PubMed1991

Improving biliary-enteric drainage in primary sclerosing cholangitis: experience with endoscopic methods.

Six jaundiced patients with primary sclerosing cholangitis and a dominant biliary stricture were managed by endoscopic placement of endoprostheses. Five showed considerable improvement within weeks of stenting: their serum bilirubin concentration fell from mean (range) 266 mumol/l (63-681) to 65 mumol/l (10-280) after one month. One patient required a liver transplant at five months because of continued deterioration in hepatic function. Follow up of 12-49 months in the remaining five patients shows sustained biochemical improvement, with repeat cholangiograms indicating doubling of the minimum calibre of the extrahepatic bile duct in four patients and considerable shortening of stricture length in three. Three patients developed sepsis at the time of the initial endoprosthesis insertion: surgical drainage was necessary in one. Endoscopic methods of improving biliary-enteric drainage in jaundiced patients with primary sclerosing cholangitis may be preferable to surgical and percutaneous methods, which may complicate subsequent liver transplantation.

Adult↗
PubMed1990

[Should fragments of stone expelled after extracorporeal lithotripsy always be analyzed?].

The morphological and constitutional analysis of renal stone fragments expelled after extracorporeal shock wave lithotripsy enables the structure and morphological type of stones to be reconstructed in 92.8 per cent of the cases as regards surface and section and in 74.5 per cent of the cases down to the core. A study of the molecular and crystalline composition of such fragments demonstrated the preponderance of whewellite in both sexes (men 85.4 per cent; women 72.4 per cent). The frequency of weddellite was 1.6 times higher in men (73.8 per cent) than in women (44.8 per cent), and the frequencies of struvite and ammonium urate were 2.8 and 2.6 times respectively higher in women than in men, despite a significant fall in frequency as compared to a previous series. Correlations between morphological type of stone and biochemical data (when available) could be established in 84 per cent of the cases. This made it possible to initiate treatments aimed at preventing recurrences, the cost of these treatments in the long term being lower than that of the curative urological treatments, including extracorporeal shock wave lithotripsy.

Adult↗
PubMed1990

Differential expression of transferrin receptor in duodenal mucosa in iron overload. Evidence for a site-specific defect in genetic hemochromatosis.

In genetic hemochromatosis, metabolic studies have demonstrated inappropriately increased iron absorption by cells of the duodenal mucosa. It is not clear whether this reflects an intrinsic abnormality of iron homeostasis at this site or is a consequence of a more generalized defect in cellular iron metabolism particularly involving the liver. We have previously used the expression of iron-related proteins as markers of iron homeostasis and have demonstrated normal regulation of the transferrin receptor and ferritin in the liver in this condition. In the present study we used immunohistochemical techniques to study transferrin-receptor expression in the gastrointestinal epithelium in normal subjects and patients with iron overload. In untreated genetic hemochromatosis and normal subjects, villus epithelial cells expressed receptor in the basolateral, subnuclear region. In contrast, in patients with secondary iron overload, receptor staining was absent in villus epithelial cells. The cells in the duodenal crypts showed intense staining for the transferrin receptor in all subjects investigated, a finding consistent with the known behavior of this receptor in proliferating cells. Given that body iron stores in both types of iron overload were comparable, these findings indicating a failure of down-regulation of the villus enterocyte transferrin receptor in genetic hemochromatosis may reflect the presence of a regulatory defect associated with the inability to control iron absorption in this condition.

Adult↗
PubMed1990

Circulating osteocalcin in primary biliary cirrhosis following liver transplantation and during treatment with ciclosporin.

Circulating osteocalcin, a non-collagen bone protein is considered a useful indirect index of turnover. Osteocalcin levels were measured by radioimmunoassay in 57 female patients with primary biliary cirrhosis (PBC) from two centres, 52 normal female controls, 11 female patients following liver transplantation for PBC and seven female patients with PBC treated with Ciclosporin. Serum levels were significantly less in the PBC group (median 10 ng/ml) compared to normals (median 15 ng/ml: p less than 0.001). Patients with PBC treated with Ciclosporin had significantly higher levels than untreated patients (median 23 ng/ml: p less than 0.001). Levels also increased significantly following transplantation when all patients were receiving Ciclosporin (median 40 ng/ml: p less than 0.001). The results suggest that the abnormal bone metabolism of PBC is significantly altered by Ciclosporin and liver transplantation.

Adrenal Cortex Hormones↗
PubMed1990

[Carcinosarcoma and spindle cell carcinoma of the bladder. A comparison of 2 cases with an immunohistochemical study].

These two cases of bladder tumours with an unusual histological appearance were observed at Hôpital Saint-Louis in 1988. They contained two cellular components: the usual epithelial type and a spindle cell type. Immunohistochemistry performed in order to identify the various cell contingents established the diagnoses of carcinosarcoma and spindle cell carcinoma and emphasised the differences and similarities between these two entities, which we believe can be differentiated.

Aged↗
PubMed1990

Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine.

Iron-withholding by the chelating agent desferrioxamine abrogates the proliferative response of human peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA). The present study investigated whether desferrioxamine operates late in the activation process or, as recently suggested, at an early stage, by inhibiting the appearance of the interleukin-2 (IL-2) receptor. Human PBMC were stimulated with PHA (10 micrograms/ml) and [3H]thymidine ([3H]TdR) incorporation determined after 66 hr of culture. Greater than 90% inhibition was achieved by concentrations of desferrioxamine as low as 5 mumol/l present throughout culture, while IL-2 receptor expression (anti-Tac), analysed by FACS, was maintained at up to 75% of control levels. 300 mumol/l desferrioxamine present throughout culture abrogated [3H]TdR incorporation and additionally suppressed IL-2 receptor to 10-15% of control levels. In contrast, the same high dose of desferrioxamine when added for 2 hr to cells previously cultured for 66 hr produced 80% inhibition of [3H]TdR incorporation but failed to inhibit expression of the IL-2 receptor. Desferrioxamine rapidly achieved equilibrium across the cell membrane (within 60 min) and chelated 59Fe delivered to activated cells by the transferrin endocytic cycle. These results indicate that desferrioxamine can inhibit T-cell activation either early or late in the process by chelating iron and independently of an effect on the IL-2 receptor. In support of a dual effect of the drug is the finding that at 50 mumol/l, desferrioxamine-enhanced expression of the transferrin receptor occurred, an adaptive response made to intracellular iron depletion, while IL-2 receptor expression was inhibited.

Cell Division↗
PubMed1989

Cytogenetic study on eleven cutaneous neoplasms and two pre-tumoral lesions from Xeroderma pigmentosum patients.

Eleven independent tumors (5 basa-cell carcinomas, 5 squamous-cell carcinomas and 1 malignant melanoma), 2 pretumoral lesions and one common nevus, developing in the skin of 10 unrelated XP patients were cytogenetically analyzed. No specific chromosomal changes were observed. Two features were relevant, however: emergence of several independent clones and over-involvement of telomeric and centromeric regions in the formation of chromosomal rearrangements. Jumping translocations were observed in 2 squamous-cell carcinomas involving telomeric and centromeric regions.

Adolescent↗
PubMed1989

Regulation of the hepatic transferrin receptor in hereditary hemochromatosis.

The liver is the main site of iron accumulation and pathologic sequelae in hereditary hemochromatosis. Whether this is a result solely of inappropriately increased absorption of iron by the gastrointestinal tract or a more generalized regulatory failure of iron balance is unknown. Using immunohistochemical techniques, we have examined the effects of therapeutic changes in liver iron stores on the expression of the hepatic transferrin receptor in hereditary hemochromatosis. Ten patients with untreated hereditary hemochromatosis had no detectable staining for transferrin receptor in their liver biopsies. All had increased hepatic ferritin (mean = 19.9 micrograms per mg protein, range = 1 to 31.7 micrograms per mg protein) and hepatic iron levels (mean = 36.2 micrograms per mg protein, range = 3.6 to 69.9 micrograms per mg protein). In contrast, hepatocyte transferrin receptor was detected in seven patients in whom hepatic iron stores were markedly depleted by venesection (hepatic ferritin mean = 0.32 microgram per mg protein, range = 0.16 to 0.53 microgram per mg protein; hepatic iron mean = 0.98 microgram per mg protein, range = 0.3 to 2.1 micrograms per mg protein). Sequential data from one patient confirmed the reexpression of receptor in response to therapeutic iron depletion, whereas data from another patient studied during treatment illustrated a reciprocal relationship between liver tissue distribution of iron and expression of transferrin receptor. The finding that appropriate physiologic regulation of the hepatic transferrin receptor operates in hereditary hemochromatosis does not support the concept of a generalized defect in receptor-mediated uptake of transferrin-bound iron.

Antibodies, Monoclonal↗
PubMed1989

Optimizing the immunohistochemical signal from the transferrin receptor in liver tissue.

Cellular expression of the transferrin receptor is determined by the proliferative state and iron requirements of the cell. Previous immunohistochemical studies using a number of anti-(transferrin receptor) monoclonal antibodies confirmed the biochemical evidence that hepatocytes express the receptor, although the distribution shown was patchy with only a small number of cells showing positive staining. In the present study, a number of techniques have been compared to optimize detection of the immunohistochemical signal from the transferrin receptor in human liver tissue. Using an alkaline phosphatase detection system, widespread expression of this receptor with both cytoplasmic and membrane staining was found in all parenchymal and non-parenchymal cells.

Alkaline Phosphatase↗
PubMed1989

Autoreactivity to hepatocellular antigens in primary biliary cirrhosis and primary sclerosing cholangitis.

To investigate the possible involvement of autoimmune reactions in the periportal hepatocellular damage that is often seen in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), sera from 35 patients with PBC and 31 with PSC were tested for autoantibodies against the liver-specific lipoprotein preparation, LSP, and against one of its liver-specific constituents, the asialoglycoprotein receptor (ASGP-R), and compared with results in 24 untreated patients with autoimmune chronic active hepatitis (AI-CAH). Anti-LSP antibodies were found in 48.5% of the PBC and 10% of the PSC patients, vs. 100% of those with AI-CAH, while anti-ASGP-R was found in 23% of PBC, 10% of PSC and 96% of AI-CAH patients. In PBC (but not in PSC) these antibodies correlated with severity of periportal inflammation and piecemeal necrosis but tended to be associated with the later stages of the diseases and both seropositivity for, and titres of, anti-LSP and anti-ASGP-R were significantly influenced by the presence of HLA DR3 (positively) and DR2 (negatively) in these patients. DR3 was also associated with significantly higher, and DR2 with lower, serum IgG concentrations in PBC. The findings suggest that, in PBC, DR2 and DR3 may be associated, respectively, with one or more genes that code for down-regulation or for elevation of overall immunoresponsiveness and that autoreactivity to hepatocellular antigens in PBC is more likely to be a consequence than a cause of hepatocellular injury. Periportal liver damage in PSC seems to involve different mechanisms.

Asialoglycoprotein Receptor↗
PubMed1989

[Ureteral flushing].

Flushing back stones of the lumbar or iliac ureter towards the renal cavities by means of a catheter is now part of everyday practice. The ureteric flush-back technique is often easily performed when the appropriate equipment is used wisely. We used a 23 Ch cystoscope with a 5 degrees lens to work in the axis of the ureter and a 7 Ch catheter with a single orifice is advanced as far as the stone. In 30% of cases, the stone immediately ascends as far as the renal cavities due to ureteric distension. In the case of failure, rapid injections of physiological saline with a syringe are successful in 40% of cases. In 10% of cases, success depends on progressive hydraulic distension of the ureter above the stone following injection of physiological saline.

Cystoscopy↗
PubMed1988

Chromosome imbalance in endometrial adenocarcinoma.

The results of karyotypic analysis by R-banding after short-term culture of eight new cases of endometrial adenocarcinomas are presented and compared to previously published data. Among a total of 25 cases reported that had a diploid or near-diploid chromosome number, 72% contained a trisomy or tetrasomy 1q, often as the only abnormality. An excess of the long arm of chromosome 1 is, therefore, shown to be the predominant feature of endometrial adenocarcinoma. Trisomies 10, 2, 7, and 12 were, in decreasing order, the most frequently associated abnormalities, but trisomy 10, found in 40% of the cases, can also exist as the only imbalance. Because breakpoints in chromosome 1 are generally centromeric, a position effect with oncogene activation seems unlikely. It is suggested that the observed chromosome imbalances are secondary and are the result of the adaptation of the cancer cell to disturbed metabolic pathways.

Adenocarcinoma↗