Biomedical subjects
Publications and source records attributed to J Rahier.
We report a case of gastric enterochromaffin-like carcinoid tumour associated with fundic chronic atrophic gastritis and hypergastrinaemia of antral origin. The clinical and pathological features of this association are reviewed. The probable causal relationship between these argyrophil carcinoids and hypergastrinaemia is also discussed.
Nonhistone nucleoproteins associated with the nucleolar organizer regions (NORs), the genes coding for the ribosomal RNA precursor, can be visualized by silver staining. The black dots (AgNORs) appearing on the nuclei are thought to reflect cell differentiation. In this study, AgNORs were counted and their area was measured and compared with the area of the nuclei in normal and carcinomatous cells of the uterine cervix. The number of AgNORs per nucleus was significantly higher in the endocervical than in the basal exocervical epithelium (p less than 0.005) and in the carcinomatous epithelium, either in situ or invasive, than in both normal epithelia (p less than 0.002). Individual AgNORs were significantly smaller in carcinoma in situ than in endocervical epithelium (p less than 0.05) or in invasive carcinoma (p less than 0.01). Significant differences were also found in the total AgNORs area per nucleus between the following groups: basal exocervical versus endocervical epithelium (p less than 0.01), basal exocervical and endocervical epithelium versus invasive carcinoma (p less than 0.001), and in-situ versus invasive carcinoma (p = 0.02). The conclusions are that the number and the total area of AgNORs per nucleus increase with the differentiation of the cell or with its carcinomatous transformation, but no prognostic significance can be drawn so far from our measurements.
There is a general agreement on the cell specificity of gastrin processing. In order to investigate this processing in Zollinger-Ellison (ZE) patients, we have studied in two primary gastrinoma cultures (one from a pancreatic tumor, the other from a liver metastasis) the proportion of progastrin fragments using immunochemical and immunohistological methods. In tumor extracts as well as in sera, the predominant gastrin form differed between the two patients (i.e. being G17 and G34, respectively). In the two gastrinoma cultures, RIA determinations and electron microscopic observations indicated that the proportion of progastrin increased with time while that of G17 and G34 decreased. On the other hand, as the culture time extended, an increasing proportion of nonimmunostained secretory granules was observed suggesting the presence of other gastrin precursors (e.g. Gly-extended progastrin). From these findings, we suggest that gastrinoma culture cells could be a valuable tool in the biochemical approach to gastrin processing in ZE tumors.
In the present study, we investigated whether the analysis of cells and proteins collected by bronchoalveolar lavage (BAL) could accurately reflect the degree of functional impairment in pulmonary sarcoidosis. Eighteen patients with biopsy-proven sarcoidosis were prospectively evaluated. An inverse relationship was demonstrated between BAL coefficient of excretion relative to albumin (RCE) values of IgG and IgA and diffusion for carbon monoxide (Dco). A similar negative correlation existed with PaO2 at the end of a maximal exercise. Steroid therapy in five patients lowered concomitantly BAL RCE of IgA and IgG while Dco values increased. Immunoperoxidase studies in three lung biopsies revealed numerous Ig-containing cells within the lung parenchyma. We suggest that these BAL Ig values reflected the mononuclear cell infiltration of the bronchiolovascular sheaths and lung interstitium. This cellular infiltration likely induces a distortion of the capillary bed and may affect the gas exchanges in a reversible way.
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The characterization of the tumors and their metastasis in patients with the Zollinger-Ellison syndrome is currently based on the immunohistochemical identification of gastrin cells. However, sometimes tumoral cells fail to react with common C-terminal gastrin antibodies. In order to clarify this failure, we carried out morphologic, morphometric and immunocytochemical analyses performed on light and electron microscope levels of 6 pancreatic and 1 metastatic gastrinomas, using antibodies raised against various sequences of human progastrin. On the basis, in light microscopy, of qualitative analysis of immunostaining within cells and of immunostained cell numbers, gastrin 34 residue seemed to be the prominent form in 2 of the tumor tissues, G-17 in 1 tumor which was not responsive with C terminus progastrin and N terminus G-34 antisera, and progastrin in the metastatic tissue that did not contain typical gastrin (G-like) cells. Two tumors failed to react with all antisera used. At the electron microscope level, immunogold staining revealed that progastrin was present only in the progranules and gastrin 34 in both progranules and intermediate granules. Quantitative studies performed on 3 tumors showed that, within a given tumoral cell, about 25 percent of progranules contained progastrin while 75 percent contained gastrin 34. We concluded that different forms of gastrin can be immunodetected in a gastrinoma tissue, depending on the regions, and that the distribution of progastrin fragments is variable from tumor to tumor. So, specific antibodies to different fragments of progastrin may help to the characterization of gastrinomas.
The children's liver transplantation program at the University of Louvain Medical School in Brussels has been organized with a multidisciplinary pediatric approach. The age distribution of the first 139 patients transplanted between March 1984 and June 1989 is characterized by the distinct preponderance of infants and small children (62.5% younger than 3 years, 16 younger than 1 year). Biliary atresia unalleviated by the Kasai portoenterostomy or its modifications was the single most frequent indication (101 cases) followed by the heterogenous group of metabolic diseases (17 cases). Two children underwent combined liver and kidney transplantation. A prominent feature of this series is the routine use of the reduced-size liver (40% of the 171 grafts) to alleviate the shortage of size-matched pediatric donors. The actuarial survival rate of the 139 children was 75.8% at 1 year and 72.4% at 2 years and thereafter. For patients who received 1 graft electively, the 1-year survival rates were 85.2% and 92.5% for those who received a full-size or a reduced-size liver with the same proportion (83%) of long-term surviving patients having normal liver tests. Long-term survival rates were not influenced by age, except for infants younger than 1 year with 62.4% surviving at 1-year posttransplantation. This latter group included a vast majority (14 of 16) of severely debilitated biliary atresia cases in preterminal condition. Graft loss from rejection was kept at a low rate of 5.2% (acute in 5-2.9% and chronic in 4-2.3%).
Our aim was to determine whether density of immunolabeling can be used to estimate the amount of an antigen in a tissue. The biological model was the pancreatic insulin-containing B cell. The insulin content of the pancreas of Wistar rats was decreased by five injections of glibenclamide (0.5, 1, or 2 mg/kg) every 12 hours. After resection of the whole pancreas specimens were taken for insulin extraction and measurement by radioimmunoassay and for immunocytochemistry. The sections were treated either by a polyclonal anti-insulin serum at 1/500 or 1/3000 and peroxidase-antiperoxidase complex or by a monoclonal anti-insulin serum at 1/500 and indirect immunoperoxidase. Peroxidase was revealed by diaminobenzidine. The density of immunostained B cells was determined with an automatic image analyzer (Ibas 2000, Kontron, FRG). Compared with controls, pancreatic insulin concentration was decreased by about 40, 60, and 85% in rats treated by the three doses of glibenclamide. A strong correlation was found between the insulin concentration and the optical density of islets under certain conditions: with the monoclonal anti-insulin serum (r = 0.90) and with the polyclonal anti-insulin serum at a high dilution (r = 0.95) but not at a low dilution (r = 0.13). With the latter, the optical density was high even in islets with reduced insulin content. In conclusion, a low dilution of antiserum should be used to detect cells with a small amount of antigen, whereas a higher dilution makes it possible to estimate the antigen concentration in the tissue. Thus, under appropriate conditions, a linear relationship exists between the optical density of the immunostained material and the concentration of immunoassayable antigen. This technique may thus prove useful in evaluating the functional state of cells, in particular secretory cells, under normal or pathological conditions.
A literature review was conducted in relation to a case of chronic diarrhea associated with a VIP (vasoactive intestinal polypeptide) producing ganglioneuroblastoma (GNB), in an 18-month old female baby. This is a rare entity characterized by premonitory, persisting diarrhea, causing fluid and electrolyte changes typical of the WDHA syndrome, associating watery diarrhea, hypokalemia, and achlorhydia. Elevated VIP plasma levels are an indication for an echographic and/or CT-scan search for the causal secreting tumor. Although the prognosis of this condition seems favorable, the recommended treatment is surgery. The VIP substance represents an excellent biological monitoring marker. Ganglioneuroblastomas are tumors of the sympathetic nervous system, which, according to Pearse's cell and embryologic theory (1966), have to be linked to the APUD system tumors (paraneuromas). VIP-producing forms are rare in children, and only 29 case studies have been compiled in the literature since 1970, when the VIP substance was discovered. The case reported in this study illustrates the diagnostic problems raised by such lesions, and allows us to confirm VIP's imputability for the occurrence of the chronic diarrhea condition in this child.
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A 52-year-old man, having been treated for 4 months with chlorpropamide for diabetes mellitus type II, developed severe cholestatic hepatitis following a short course of erythromycin ethylsuccinate. Despite prompt withdrawal of both drugs, the cholestatic picture worsened and was associated with morphological evidence of disappearing interlobular bile ducts. After a 2-year course of profound cholestasis complicated by steatorrhea and striking hyperlipidemia, the patient died of ischemic cardiomyopathy. It is believed that this is the first published case of irreversible cholestasis with disappearance of ducts potentially related to a metabolic interaction between erythromycin ethylsuccinate and chlorpropamide.
During pregnancy in mice, three groups of corpora lutea (CL) originating from 4 successive ovulatory cycles could be distinguished taking into account their size, cellular structure and stain affinity. Type I CL originated at the onset of pregnancy, type II CL originated during the 2 previous estrous cycles and type III CL were produced during a cycle preceding the two others. CL volume of type I increased 10-fold between day 0 and day 18.5, a 2.5-fold increase in volume occurred in type II CL between day 0 and day 3, although they derived from cycles preceding pregnancy. The volume of type III remained unchanged. This fact suggested that types I and II CL probably play a functional role in the ongoing pregnancy. After day 10 of pregnancy a high correlation coefficient (r = 0.933) is observed between type I CL and the number of embryos in the corresponding uterine horn.
Pediatric liver transplantation in Europe has expanded rapidly during the last four years. The survival rate of the 254 children less than 15 years recorded in the European Registry on December 31, 1987 was 68% at one year and 61% at three years; nineteen centers have contributed to this activity, of which 11 had performed less than 5 cases each while two thirds of the experience was concentrated in three centers (Brussels, Cambridge, Hannover). The results obtained in the first 100 children (65% were younger than 3 years) who received a liver graft at the University of Louvain Medical Center in Brussels between March 1, 1984 and July 31, 1988 are reported. The survival rates (79% at one year and 73% at three year) which do not differ with regard to the age, the indication of the technical modalities (whole liver or reduced size livers) are strongly influenced by the clinical condition (84% vs 50% at one year in elective and emergency transplantations respectively). One third of the 122 grafts transplanted by the authors were reduced livers harvested from older and often adult donors. This technique provides results of equal quality and does not entail an increased rate of technical complications; on the contrary, the incidence of arterial thrombosis has been significantly reduced. Transplantation of a reduced size liver is safe and should be recommended even in elective conditions, in view of the dire shortage of small pediatric donors.
Polymorphonuclear leukocytes may participate in reperfusion injury. Whether leukocytes affect viable or only irreversibly injured tissue is not known. Therefore, we assessed the accumulation of 111In-labeled leukocytes in tissue samples characterized as either ischemic but viable or necrotic by metabolic, histochemical, and ultrastructural criteria. Six open-chest dogs received left anterior descending coronary occlusion for 2 hr followed by 4 hr reperfusion. Myocardial blood flow was determined by microspheres and autologous 111In-labeled leukocytes were injected intravenously. Fluorine-18-2-deoxyglucose, a tracer of exogenous glucose utilization, was injected 3 hr after reperfusion. The dogs were killed 4 hr after reperfusion. The risk and the necrotic regions were assessed following in vivo dye injection and postmortem tetrazolium staining. Myocardial samples were obtained in the ischemic but viable, necrotic and normal zones, and counted for 111In and 18F activity. Compared to normal, leukocytes were entrapped in necrotic regions (111In activity: 207 +/- 73%) where glucose uptake was decreased (26 +/- 15%). A persistent glucose uptake, marker of viability, was mainly seen in risk region (135 +/- 85%) where leukocytes accumulation was moderate in comparison to normal zone (146 +/- 44%). Thus, the glucose uptake observed in viable tissue is mainly related to myocytes metabolism and not to leukocytes metabolism.
We report five cases of asymptomatic patients with persistently abnormal liver function tests in whom copper metabolism abnormalities resulted in a misleading suspicion of Wilson's disease. Ceruloplasmin levels assessed by nephelometric immunoassay, single radial immunodiffusion and the enzymatic method averaged 53.8, 61 and 52.8% of the mean value obtained in age- and sex-matched controls (p less than 0.001). Twenty-four-hour urinary copper excretion was higher than the normal range in three instances. Four patients exhibited hypertriglyceridemia. Liver histology showed fatty change with or without sinusoidal fibrosis. Electron microscopic examination unexpectedly disclosed mitochondrial and lysosomal changes identical to those described in Wilson's disease. The present observations indicate that biochemical and ultrastructural changes suggestive for Wilson's disease may be observed in the absence of increased liver copper content. Whether such cases represent isolated cases of heterozygosity for the Wilson's disease gene remains to be elucidated.
Insulin, glucagon, somatostatin and pancreatic polypeptide cells were quantified after immunoperoxidase staining in sections of pancreases obtained from nine control subjects and seven diabetic patients with primary or secondary iron overload. One was normoglycaemic, two had glucose intolerance and four presented insulin-requiring diabetes. The whole pancreas was studied, taking into account the heterogeneous distribution of the endocrine cells. In the diabetic patients, the weight of the pancreas tended to be lower. Iron overload predominated in the exocrine tissue, whereas in islets iron concentration was quite variable from case to case. At the Haemalun-Eosine staining the histological appearance of the islets was normal, their shape and size being unchanged; amyloid deposits were absent, as were atrophic islets. Immunoperoxidase staining revealed a severe reduction in the number of immunoreactive B cells in the four diabetic patients. The mass of immunoreactive B cells was calculated from their volume density and from the weight of each lobe of the pancreas. It averaged 950 mg in control subjects, 1580 mg in the normoglycaemic patient, 1010 mg in patients with glucose intolerance and 180 mg in insulin-requiring diabetic patients. The electron microscopic examination, performed in four cases, revealed that the iron deposits were restricted to B cells and associated with progressive loss of their endocrine granules. The study shows that the pancreatic islet abnormalities in iron overloaded diabetic patients are completely different from those of Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients. This constitutes a further argument for a specific role of iron in the pathogeny of diabetes in haemochromatotic patients.
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