[Significance of erythrocyte antigen K of Kell's system for blood transfusion. Discussion and conclusion to preceding contribution].
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Biomedical subjects
Publications and source records attributed to H Fiedler.
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Chickens were injected posthatching with cyclophosphamide in three different doses (total 8, 10, 11 mg). Histomorphological analysis of bursal tissue was performed up to 11 weeks of age. A probable biphasic recovery was observed in the majority of the chickens. The first phase of recovery is characterized by the appearance of solitary thioninophilic cells in reticuloepithelial follicles, followed in a few follicles by a redevelopment similar to embryonal follicular genesis. The late phase of recovery starts from week 7 on by infiltration of reticuloepithelial follicles with mature plasma cells in the manner of a peripheral lymphoid organ followed by thioninophilic lymphoid cells. The latter cells populate the follicles successively. Different transitions to normal follicles then take place. These investigations confirm observations of a reconstitution of bursal compartments starting some weeks later than the recovery of thymus, which takes place 2 weeks after cyclophosphamide treatment.
The present study was done to characterize the hormone secretion and content of isolated rat islets in organ culture dependent on the glucose concentration and the number of cultivated islets per culture bottle (10 or 30). For the calculation of the recovery rate the glucagon and insulin breakdown in the culture medium containing 10% calf serum was assayed. The glucagon recovery after incubation for 24 h at 37 degrees C varied from 2 to 92% and that of insulin from 75--105% depending on the serum batches. The cultivated islet responded to 16 mmol glucose by a significant enhancement of insulin release, whereas the glucagon release was not influenced. The glucagon release fell progressively with the duration of cultivation. 2 mmol dibutyryl cyclic AMP augmented insulin and glucagon release in the presence of 5 and 16 mmol glucose and significantly enhanced the glucagon content in the cultivated islets.
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The effect of various inhibitors of insulin secretion such as mannoheptulose (20 mM), atropine (1 mM), diphenylhydantoin (20 microng/ml), high concentration of Mg++ (5.3 mM) in the presence of 20 mM glucose (control) on insulin content and secretion from collagenase-isolated rat pancreatic islets was studied in vitro by cultivation of islets up to 5 or 9 days in glass Petri dishes without attachment. In a following short-term incubation for 60 min the glucose-induced insulin release without and with theophylline (5 mM) was investigated. Islets cultivated at 5 mM glucose and at 20 mM glucose with the inhibitors mannoheptulose or atropine lost the responsiveness to glucose and theophylline whereas such islets cultivated at 20 mM glucose alone or with diphenylhydantoin (DPH) or 5.3 mg Mg++ showed a stimulation of insulin secretion by glucose and theophylline. Compared, however, with freshly isolated islets all cultivated islets were restricted in their maximal glucose response and this defect was not evoked alone by quantitative changes in islet insulin content. Nevertheless, culture conditions which facilitate a net increase of insulin (content and release) during cultivation influenced also positively the glucose-induced insulin release without and with 5 mM theophylline in the following short-term experiments.
By feeding a regular laboratory chow, sand rats (Psammomys obesus) from our breeding colony gained different body weights, though they received approximately the same quantity of calories. Sand rats, reaching a body weight above 160 g (group B) showed significantly increased blood glucose values in contrast to the animals with a body weight under 160 g (group A). Isolated pancreatic islets of these two groups of sand rats were incubated with [3H]-leucine to study the incorporation of this amino acid into proinsulin and insulin. The incorporation into proteins of pancreatic islets of sand rats of group B was stimulated by 0.45 mg and 3.0 mg/ml glucose. In group A there was no further stimulation from 0.45 mg to 3.0 mg/ml glucose. Insulin secretion could be stimulated by glucose in both groups, but the stimulation was stronger in group B than in group A.
Colony-bred sand rats were fed with rat pellet chow in restricted quantities or ad libitum for 8--10 or 28--31 weeks after weaning. The changes of glucose metabolism were characterized by an intraperitoneal glucose tolerance test. The daily food intake and the average weight gain differed only in the first 5--7 weeks of pellet nutrition. In the impaired glucose tolerance tests of all sand rats the high basal plasma IRI levels were not significantly increased by the grossly enhanced blood glucose concentrations. The insulin secretion of either acutely incubated or for 8 days cultivated isolated pancreatic islets, however, was stimulated already by low (1.7 and 5 mM) glucose concentrations in all diet groups. Otherwise the glucagon secretion of isolated islets was not suppressed by high glucose concentrations. No changes of insulin or glucagon contents of islets were found in the different diet groups. The adipocytes of all animals revealed a complete ineffectiveness of insulin on the glucose utilization to CO2 and triglycerides. The basal glucose conversion to CO2 and glycogen in skeletal muscle and the stimulatory potency of insulin was low and not distinctly different in all groups. In liver glycogen and triglyceride contents as well as gluconeogenic enzyme activities were not influenced by feeding of different quantities of pellet diet at the investigated time points. The time course of the metabolic and clinical alterations demonstrates that the peripheral organs become insensitive to insulin in the first weeks after weaning.
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No diabetic angiolopathy was found in the retinas, kidneys and skeletal muscles of protodiabetic and overtly diabetic sand rats. The terminal blood vessels were investigated using histological, enzyme histochemical, immunofluorescence microscopic, autoradiographic and electron microscopic methods. There seems to be little or no connection in sand rats between the diabetic metabolism syndrome and the metabolic process leading to angiolopathy.
Sand rats, captured in Egypt and fed with a low caloric vegetable diet during adaptation, were investigated before and after 2.5 and 8 weeks diet treatment (30 and 40 kcal/100 g body weight daily). In hexobarbital anaesthesia the sand rats were loaded with 1 g glucose/kg body weight in a single dose intravenously. After a rapid increase the content of glucose in blood remained at a level of about 600 mg glucose/100 ml blood. The insulin immunoreactivity in blood did not change uniformly after application of glucose and remained in a physiologic range. In the islets of Langerhans a degranulation was found during diet treatment. The sensitivity of the epididymal adipose tissue towards insulin in vitro decreased to a nearly complete resistance in the course of diet treatment. A diminution of insulin sensitivity was also found in the m. soleus in vitro. The content of glucose-6-phosphate in the m. semimembranosus was found enhanced after the preparation of the animal. It was found progressively increased up to the five-fold at the end of diet treatment. In the corresponding muscle the glucose distribution volume was increased to about double the extracellular volume. An accumulation of free glucose within the muscle cell must be taken into account. In conclusion the treatment of sand rats with a diabetogenic diet results very quickly in a loss of insulin sensitivity of adipose tissue. The progressively increased stress-mediated accumulation of glucose-6-phosphate and free glucose refers to an inhibition of glucose utilization in the phosphorylation step of glucose in skeletal muscle.
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In the period between 1965-1974 564 patients with gastrointestinal hemorrhages were admitted in the medical clinic of the District Hospital St. Georg Leipzig. Of them 112 patients (20%) were at once or after failure of a conservative therapy admitted in the surgical clinic for operation. 82 patients died (18%) of the conservatively treated patients). The most frequent sources of haemorrhage duodenal ulcers with 32%, ventricular ulcers with 25% and carcinomas of the stomach with 19%. In 13% of the patients haemorrhages induced by drugs could be assumed. In 13% the case were recidivation haemorrhages. Severe gastrointestinal haemorrhages were observed only in 4% of the patients and consequently were less important in our patients. A further improvement of the diagnostic exactness is possible by perfection of the early diagnosis (emergency gastroscopy and angiography), which may be important with regard to a surgical intervention.
The demonstration of monomeric complexes of fibrin in the blood is regarded as a secure sign of an increased consumption of coagulation factors in the sense of a consumption coagulopathy. As a simple and sensitive method for the demonstration of these intermediate products of the coagulation the protamine sulphate test proved its worth in clinical practice. The subjective judgment of this test-tube test frequently becomes difficult in the borderline region between normal and pathologic. On the basis of own comparative investigations it could, however, be demonstrated that by means of photometric measurements an objective and exact evidence about the result of the protamine sulphate test can be made. It is referred to the advantages in the judgment of the course of a consumption coagulopathy during the treatment.
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The secretion of insulin and glucagon was investigated in pancreatic islets from diabetic and nondiabetic sand rats of similar age and weight. The metabolic characterization was based on an intraperitoneal glucose tolerance test. Compared to nondiabetic animals diabetic sand rats had a diminished insulin content in their islets and a decreased insulin secretory response to glucose, glyceraldehyde and theophylline. Diazoxide inhibited insulin release in diabetic as well as in nondiabetic sand rats whereas mannoheptulose was effective only in the nondiabetic rats. There was no significant difference in glucagon content between the two groups. The glucagon secretion by pancreatic islets of diabetic animals was not suppressed by glucose, as in nondiabetic sand rats islets, but by glyceraldehyde. This indicates that the sensitivity to glucose rather than the suppressibility of glucagon release was altered.
In Egyptian sand rats (Psammomys obesus) fed with native food and a low caloric vegetable diet after capture it was possible to study endocrinologic and metabolic changes of the early stages during the progression to diabetes. According to body weight gain and fasting blood glucose the animals were differentiated into two groups classified as basic and protodiabetic group, respectively. Isolated pancreatic islets as well as the perfused pancreases of sand rats responded to low concentrations of glucose with high insulin release during early stages of the development to diabetes. Changes in the insulin content of the islets could not be detected at this time although in the B-cells of the protodiabetic animals a degranulation was visible. During these early stages of the development to diabetes the in vitro insulin action on glucose utilization in soleus muscle and especially in epididymal fat pads as well as the basal glucose metabolism in adipose tissue were low. This strikingly reduced utilization of glucose by adipose and muscle tissues may be a factor which challenges the B-cell.
Sand rats develop a diabetes-like syndrome, connected with temporary hyperinsulinism, when fed a rat laboratory chow diet. The conversion of proinsulin to insulin is not disturbed in these animals. Sand rat islets do not secrete newly synthesized (pro) insulin preferentially. Time course and glucose response of [3H]-leucine incorporation are different between islets of sand rats and Wistar rats.
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