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Biomedical subjects

M Löhr

Publications and source records attributed to M Löhr.

At least 19 recordsLinked to original sources
PubMed1992

Human cytomegalovirus in the pancreas of patients with type 2 diabetes: is there a relation to clinical features, mRNA and protein expression of insulin, somatostatin, and MHC class II?

Human cytomegalovirus (HCMV) was recently demonstrated in the pancreas of about half the patients with type 2 diabetes mellitus in the absence of mumps, rubella or Coxsackie B virus. The present study addresses the question as to whether type 2 diabetes with an HCMV-positive pancreas differs from those with HCMV-negative pancreases with respect to age, sex, treatment, duration of disease, volume densities of B-cells and D-cells, mRNA levels of insulin and somatostatin, islet amyloid peptide deposits and major histocompatibility complex (MHC) class I and class II gene transcription, and protein expression. HCMV-positive type 2 diabetic patients showed a tendency towards a shorter duration of disease and significantly increased levels of MHC class II on RNA. In addition, expression of MHC class II product (HLA-DR) was identified in duct epithelial cells and/or islet cells in 9 diabetic pancreases and in 2 non-diabetic glands. No MHC class I expression could be detected. No other clinical differences between HCMV-positive and HCMV-negative glands were found. All 10 HCMV-positive diabetics showed a strong expression of MHC class II mRNA in the pancreas. By immunocytochemistry, 4 of 10 demonstrated expression on the islets; three of ten also expressed MHC DR beta on ductal cells. This finding might be related to the viral infection, as only 2 of the 9 HCMV-negative patients were HLA-DR beta positive and none of the non-diabetic controls showed increased levels of MHC class II mRNA. These data suggest that HCMV infection in the pancreas is associated with type 2 diabetes. However, no conclusions as to a role of this virus in the aetiopathology of type 2 diabetes can be drawn at present.

Aged↗
PubMed1991

[Parameters of connective tissue metabolism as markers in acute and chronic pancreatitis. A retrospective study with a cohort of normal subjects].

It is suggested that during active phases of acute and chronic pancreatitis (aP and cP) a major breakdown of extracellular matrix occurs. Since our group previously established that serum levels of the precollagen-III-peptide (P-III-P) are good markers for changes in the extracellular matrix in liver disease (e.g. fibrosis and cirrhosis), we investigated whether this would also serve as a possible marker for pancreatitis. A total of 52 patients with pancreatitis were studied (aP = 17; cP = 35) and compared to 194 controls. Diagnosis of pancreatitis was done on the basis of established classifications. Concomitant diseases, e.g. of the liver, were excluded. Serum levels of P-III-P (three assays with polyclonal and monoclonal antibodies and Fab-Fragments), hyaluronic acid (HA) and laminin (LAM) were measured by RIA or IRMA. Patients with pancreatitis displayed elevated levels in all groups, when compared with the controls. Since the P-III-P-Fab RIA measures the Col1-fragment by 50%, which is considered to be a degradation product of P-III-P, this could mean that neogenesis of collagen is paralleled by degradation during the initial course of an acute episode of pancreatitis. The ratio (quotient) of P-III-P-Fab and P-III-PMoAb (nl = 127.3 +/- 27) is changed in patients with pancreatitis towards P-III-P-Fab (aP: 115.4 +/- 84.7*, cP: 94.9 +/- 21.8*, cP-I: 89.3 +/- 9.2*; * = p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity.

Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E1 analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days. At toxic doses of cyclosporin (10 and 20 mg/kg b.wt), the B-cells showed severe hydropic degeneration of the endoplasmatic reticulum and slight degranulation of the B-cells. Accordingly, the insulin secretion was markedly impaired. Administration of rioprostil ameliorated the insulin secretion significantly, but not the ultrastructural changes. At therapeutic levels of cyclosporin (5 mg/kg b.wt), the hydropic degeneration and the drop in insulin secretion were completely prevented by rioprostil. This observation might have therapeutic implications in the treatment of patients, in particular those undergoing pancreatic transplantation.

Animals↗
PubMed1989

Cystic fibrosis associated islet changes may provide a basis for diabetes. An immunocytochemical and morphometrical study.

The pancreases of 23 patients (mean age 10.5 years, range 5-22) years dying of cystic fibrosis (CF) were evaluated at autopsy by routine histology and immunostaining for changes in their endocrine cell compartment. The severely altered pancreatic tissues showed end stage CF, with either a fibrotic pattern (CF-FIB, n = 14) or a lipoatrophic pattern (CF-LIP, n = 9) prevailing. In all specimens, irrespective of the dominating pattern, the islet system was affected by marked periinsular and intrainsular sclerosis. Quantitatively, the volume densities (relative tissue components) of the parenchymal, fibrotic, fatty and total endocrine compartments as well as the four islet cell types (B, A, D, PP) were determined by point counting. Compared with controls, the CF patients (including two patients with overt diabetes and glucose intolerance, respectively) had a significantly decreased insulin (B)-cell ratio (from 64.4 to 34%) with a concomitant rise in non-B-cells (A-cells: 23.2 to 35%; D-cells: 10.4 to 22%; PP-cells; 2 to 9%). Comparison of endocrine cell ratios in CF-FIB pancreases with CF-LIP pancreases revealed no significant differences. The reduction of approximately 50% of insulin cells in CF patients with advanced disease supports the concept that destruction of exocrine tissue with concomitant fibrous disorganization of islets gradually changes the proportional distribution of the endocrine cells in favor of the noninsulin cells. This slowly ongoing process probably provides the basis for islet dysfunction, i.e. diabetes, increasingly observed in final stage CF.

Adolescent↗
PubMed1989

Increase in B-cells in the pancreatic remnant after partial pancreatectomy in pigs. An immunocytochemical and functional study.

The regenerative and functional capacity of B-cells in the remaining pancreatic tissue after surgical removal of 40%, 60% and 80% of the pancreas was examined in 7 month old pigs (three animals in each group). Prior to resection and 1, 3 and 6 weeks after surgery, basal and glucose-stimulated levels of insulin and blood glucose were determined and compared with the preoperative data and that of sham-operated controls. For quantitative morphology, the volume of the resected specimen and the residual pancreatic tissue, 6 weeks after surgery, was determined and sections evaluated by immunocytochemistry (insulin, glucagon, somatostatin, pancreatic polypeptide) combined with morphometry. In the remaining pancreas, the volume density of the B-cells was increased by 19% (1.57-1.92 after 60% resection; p less than 0.02) and 56% (1.57-2.38 after 80% resection; p less than 0.02) 6 weeks after surgery, compared with the respective resected portion of the pancreas and the controls (n = 12). The non-B-cells gained between 0-10% (PP-cells), 10-20% (D-cells) and 30-40% (A-cells) in the different resection groups. As the number of B-cells per given islet area remained unchanged (mean 4.12 cells/0.25 mm2), the increased volume density was due to an increase in cell number rather than cell size. Insulin secretion (integrated values, 0-120 min), was not significantly impaired after 40% and 60% resection (2711 +/- 250 all preoperative samples; 3215 +/- 474 40% at 6 week intravenous glucose tolerance test (IV-GTT); 1677 +/- 109 60% at 6 week IV-GTT), although the glucose levels (integrated values) were increased during the IV-GTT. The 80% resected animals showed a significant decrease in the insulin response only 1 week after surgery (integrated values: 2711 +/- 250 all preoperative samples, compared with 1250 +/- 508 1 week IV-GTT; p less than 0.05), while the integrated glucose values during IV-GTT (0-120 min) were significantly elevated throughout the observation period. These results suggest a B-cell hyperplasia in the residual pancreas after resection, which may cope with a normal functional demand, but disclose functional abnormalities when challenged with an increased glucose load.

Animals↗
PubMed1989

Nesidioblastosis of the pancreas in an adult with persistent hyperinsulinemic hypoglycemia.

The rare finding of pancreatic nesidioblastosis in an adult is described. A 43-year-old woman presented with a two-year history of hypoglycemic hyperinsulinism. Extensive diagnostic procedures revealed no insulinoma. Subtotal (75%) pancreatectomy relieved her symptoms; she has normal insulin levels 2.5 years after surgery. The pancreatic specimen revealed only discrete islet cell abnormalities, namely B-cells budding off ductular epithelium, islets in apposition to ducts, slight islet cell hypertrophy, and islet enlargement. Immunohistochemistry showed normal total endocrine cell content as well as normal proportions of islet cell subpopulations. Review of 20 cases in the literature and the authors' experience led to subtotal (75-90%) pancreatectomy as the treatment of choice. The authors conclude that the pediatric disease of nesidioblastosis may rarely occur in adults and that the paucity of histologic findings makes the exclusion of an insulinoma mandatory.

Adult↗
PubMed1989

Insulitis and diabetes are preceded by a decrease in beta cell volume in diabetes-prone BB rats.

Immunocytochemistry combined with morphometry was used to test the hypothesis that insulitis and diabetes are preceded by quantitative changes in the pancreas of diabetes-prone BB (DPBB) rats. Diabetes-resistant BB (DRBB) rats of the w-subline served as controls. In the first part of the study rats aged 15, 30, 45, and 60 days were studied. At 60 days preceding both insulitis and onset of diabetes, the DPBB rats demonstrated lower volumes of the entire pancreas, the parenchyma, the endocrine pancreas, and beta, A, and D cells. Body weights of the DPBB rats were lower than the DRBB rats from 15 days of age on. In the second part of the study, DP and DRBB rats were coreared by a foster mother to obtain weight-matched animals. Morphometric analysis at 70 days of age revealed a reduction in both the beta cell volume density and volume whereas no differences were seen in other pancreatic parameters. These results indicate that the appearance of insulitis and the later onset of insulin-dependent diabetes are preceded by a reduction in beta cell volume.

Animals↗
PubMed1989

Rioprostil, a new prostaglandin E1, prevents cyclosporin A-induced damage to endocrine and exocrine pancreas.

The possibility that rioprostil can prevent cyclosporin A-induced damage to the pancreas is investigated. Cyclosporin A is given to rats once daily intragastrically in doses of 5, 10 and 20 mg/kg body weight. These doses cause dose dependent significant reduction of insulin release and enzyme secretion from the arterially perfused isolated pancreas. The subcutaneous injection of rioprostil, 15 micrograms/kg twice daily, could completely prevent the effects of 5 mg/kg cyclosporin A on insulin release and could completely prevent the effects of 5 mg/kg cyclosporin A on insulin release and could completely prevent the effects of 5 mg/kg cyclosporin A on insulin release and could also afford significant protection from the effects of 10 and 20 mg/kg cyclosporin A on both insulin release and enzyme secretion. The cytoprotective action of rioprostil on the pancreas may have therapeutic implications.

Animals↗
PubMed1988

Differential sensitivity of rat exocrine and endocrine pancreas to cyclosporine.

The effect of 5, 10, and 20 mg/kg bw cyclosporine on rat endocrine and exocrine pancreatic function was studied. Glucose-dependent insulin secretion from the endocrine pancreas was shown to be significantly impaired 8 days after cyclosporine was given once daily at a dose as low as 5 mg/kg. CCK-8-stimulated amylase and lipase secretion were less sensitive to the noxious effect of cyclosporine being impaired at a dose of 10 mg/kg. Trypsin secretion was shown to be impaired at 20 mg/kg cyclosporine only. Our results demonstrate that cyclosporine causes dose-dependent impairment of both pancreatic endocrine and exocrine functions: the endocrine pancreas being more sensitive to the noxious action than the exocrine pancreas.

Amylases↗
PubMed1988

Prevention of toxic effects of cyclosporin on pancreatic B-cells of rats by Rioprostil, a new prostaglandin analogue.

Cyclosporin 5, 10, and 20 mg/kg bw was given to rats once daily intragastrically and caused a dose dependent, significant decrease of glucose dependent insulin release from the arterially perfused isolated pancreas, without affecting animal behaviour, weight gain, microscopic appearances of the pancreas, or kidney function. Subcutaneous injection of a new synthetic prostaglandin analogue Rioprostil 7.5 micrograms/kg bw twice daily completely prevented the effect of cyclosporin 5 mg/kg bw and protected significantly against the effects of cyclosporin 10 and 20 mg/kg bw.

Animals↗
PubMed1987

Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy.

The relationship of residual insulin positivity in chronic Type 1 (insulin-dependent) diabetes and atrophy of the exocrine pancreas to duration of diabetes, age at onset and microangiopathy was studied in 26 patients (disease duration 2 to 54 years, mean 26 years). Islets containing insulin cells were found in 13/26 pancreata. In 5/13 pancreata insulin positive cells were detected in only one lobule, while in 8/13 insulin positivity was multifocal. All patients with diabetes duration less than 11 years had residual insulin cells; whereas, the rate of insulin positivity was near 40% with diabetes duration of more than 11 and 21 years, respectively. Survival of insulin cells was not clearly related to age at onset. HLA-DR expression on insulin cells was seen in one case. Insulitis was lacking. Pancreatic volume determined in 18 patients ranged from 14-110 ml (age adjusted mean 56.3 ml) and was significantly less than that of control subjects (age adjusted, mean 89.9 ml, p less than 0.0001). Computerized morphometry of the exocrine pancreas revealed severe acinar atrophy due to a reduction in size of acinar cells. Acinar atrophy correlated neither with the degree of insulin positivity, disease duration nor severity of microangiopathy. The findings suggest that in about 40% of patients with Type 1 diabetes a small population of insulin cells may escape autoimmune destruction, irrespective of disease duration or age at onset. Though exocrine atrophy and insulin deficiency are associated, the variable extent of pancreatic atrophy could not be related to such factors as amount of surviving insulin cells, duration of diabetes or microangiopathy.

Aging↗
PubMed1987

Morphometry and immunocytochemistry.

The use of morphometry (and stereology), especially in conjunction with immunocytochemistry, in surgical and experimental pathology is reviewed. The combined use of morphometry and immunocytochemistry permits the study of secretory products and the distinction between cells that produce them, e.g., as in the pancreas. Several examples to illustrate the application of immunocytochemical techniques in morphometry are presented. For example, using this approach on the pancreas, it was shown that not only B cells, but also A and D cells, seem to undergo pathologic changes in a prediabetic organism. Since morphologic alterations may be distributional as well as quantitative, a model for the assessment and statistical evaluation of the distribution of objects within an area is discussed. Similar procedures were used to analyze the distribution of cytochrome P-450 molecules along intracellular membranes; however, special labeling techniques were necessary for this quantification in the electron microscope. Immunoenzyme cytochemically stained secretions can also be studied morphometrically, and microdensitometry and microfluorometry can also be used to quantify immunocytochemical reactions, as is shown in the analysis of the intralobular distribution of NADPH-cytochrome P-450 reductase in the rat liver. Finally, the BIVAS semiautomatic system for morphometric measurements, developed at the Department of Pathology of the University of Basel, is briefly described.

Animals↗