A monoclonal antibody that induces neuronal apoptosis binds a metastasis marker.

The cell surface molecules controlling apoptosis in cortical neurons are largely unknown. A monoclonal antibody was derived that induces cultured neocortical neurons to undergo apoptosis. A Fab fragment of the antibody, however, lacked the ability to induce cell death. The antigen was purified, and characterized by compositional analysis, fast atom bombardment (FAB) mass spectrometry, sequential exoglycosidase treatments, methylation analysis, and (1)H-nuclear magnetic resonance spectroscopy, proving to be isoglobotetraosylceramide (IsoGb4). IsoGb4 has been shown previously to be a metastasis marker, antibodies against which block metastases in a mammary adenocarcinoma model (S. A. Carlsen et al., Cancer Res., 53: 2906-2911, 1993). Addition of the purified antigen to cells lacking this glycolipid demonstrated that it is capable of functioning as a portable apoptosis-transducing molecule. Intracellular ceramide levels were increased after the treatment with the apoptosis-inducing antibody, but the membrane sphingomyelin level remained unchanged. Fumonisin B1 inhibited both the ceramide increase and the apoptosis induced via IsoGb4, which indicated that the ceramide synthase pathway is likely to be involved in apoptosis induction by IsoGb4.

[Relationship between platelet hyperactivation and dyslipoproteinemia in diabetic nephropathy]. / A diabeteses nephropathiát kísérö dyslipoproteinaemia és a thrombocyta aktiváció összefüggése.

The relationship between the secundaer hyperlipidaemia and pathological platelet activation was examined in 40 insulin-treated diabetic patients without nephropathy and 21 with nephropathy. Diabetic nephropathy was recorded with the measurements of serum creatinine, serum beta 2-microglobulin, and urine albumin excretion. Haemostasis and lipoprotein metabolism were characterized with determination of platelet aggregation, plasma beta thromboglobulin, thromboxane-B2, serum triglyceride, HDL and LDL cholesterol concentration, respectively. In the normalbuminuric group serum triglyceride and thromboxane-B2 positively correlated. In the nephropathic group serum cholesterol and beta thromboglobulin, as well as LDL and beta thromboglobulin, finally, LDL and thromboxane-B2 showed significant positive correlation. In diabetic patients without nephropathy platelet aggregate ratio was in positive correlation with the serum triglyceride, while the ED50-S elevated with the increase of serum cholesterol and LDL. The nephropathic group exhibited no such parallelisms. However, there were significant correlations of LDL with serum creatinine in both groups of diabetic patients. Our results seem to indicate that the increase of LDL could be associated with the change of LDL structure. Interactions of modified LDL and the platelet membrane might contribute to the platelet hyperactivation both in the nephropathy-free and nephropathic cases.

[Plasma and urine beta-thromboglobulin determination in the detection of thrombocyte hyperactivation in diabetic nephropathies]. / A plasma és a vizelet béta-thromboglobulin meghatározás a diabeteses nephropathiát kísérö thrombocyta hyperaktiváció kimutatásában.

Serum creatinine, immunoreactive serum and urine beta-2-microglobulin, plasma and urine thromboglobulin, plasma thromboxane-B2 levels and daily protein excretion were determinated in 61 insulin treated diabetic patients, comparing the different patient groups (complication free, nephropathy without azotaemia and nephropathy with azotaemia) with the control subjects. In the groups of all diabetic patients plasma and urine beta-thromboglobulin and plasma thromboxane-B2 levels were higher that in the controls. There was a positive significant correlation between urine beta-thromboglobulin and beta-2-microglobulin in the group without complication, and between the plasma beta thromboglobulin and beta-2-microglobulin, and plasma beta thromboglobulin and thromboxane levels in the diabetic group with azotaemia. In contradiction to some previous assumptions, the increased level of plasma beta-thromboglobulin reflects a real platelet hyperactivation also in patients with diabetic nephropathy. At the same time urine beta-thromboglobulin also increases. Determination of urine beta-thromboglobulin is more simple with less possibility of methodological error.

The possible role of tear fluid thyroxine in keratoconus development.

The normal thyroxine level in tears was found to be two orders of magnitude lower than in serum. In thyroxine function tests, keratoconus patients were found to be hypothyreotic, euthyreotic or hyperthyreotic. However, independently of their thyroid function, the tear thyroxine levels of keratoconus patients were 2-50 times higher than that of subjects free of ocular pathology. Tear thyroxine levels were higher during the progression of keratoconus and declined once corneal curvature reached a new steady value.

Late effect of tobanum and tobanum + furosemide therapy on the glucose tolerance of patients and on the insulin response to oral glucose doses.

The authors examined the effect of beta-blocker monotherapy (Tobanum tab = 5 mg cloranololum hydrochloricum) and beta-blocker + diuretic (Tobanum + Furosemide) combination therapy on glucose tolerance and insulin secretion in response to oral glucose doses in hypertensive non-diabetic patients. Twenty-six patients were examined (13 men, 13 women). The patients were followed up for 28 weeks after a 2-week drug-free period. The hypotensive dose was adjusted individually within 4 weeks. Oral glucose tolerance test and immuno-reactive insulin determination were performed concurrently before starting hypotensive therapy and on weeks 6, 14, and 28 of therapy. The results of the examinations were evaluated separately in two patient groups. Fifteen patients were given daily 10-20 mg Tobanum (Group I) while 11 patients received daily 10-20 mg Tobanum + 40-80 mg Furosemide (Group II). The glucose area of patients on Tobanum monotherapy did not change, insulin secretion decreased gradually (from 804 to 495 pmol/l). The decrease was significant (p less than 0.05). The glucose area of Tobanum + Furosemide-treated patients increased from 13.2 +/- 3.2 mmol/l to 16.1 + 4.9, the insulin secretion decreased from 1039 + 339 to 706 + 411 pmol/l during therapy (p less than 0.02 and p less than 0.05, resp.). When evaluating the results the decrease of insulin secretion is attributed to Tobanum effect while the deterioration of glucose tolerance may be correlated to the action of Furosemide on extrapancreatic metabolism.

Basal and insulin-stimulated glucose metabolism of isolated human fat cells.

Glucose-U-14C-activity added to the incubation medium of isolated human fat cells was studied for its conversion to CO2 and its incorporation into fat cell triglyceride. In view of the wide scatter of the figures found under basal conditions as well as in the presence of 100 muU/ml of insulin, the correlations of fat cell glucose metabolism to ponderal index, total body fat mass weight, mean fat cell diameter, fat cell TG-content and age were analysed. The activity of glucose metabolism in obese individuals was found to be inversely related to the degree of obesity under basal conditions as well as under the effect of insulin. According to partial regression analysis, of all these parameters it was the ponderal index which showed the most significant inverse correlation to the activity of fat cell glucose metabolism. No appreciable relationship was found between the production of CO2 from glucose and age. Incorporation of 14C-activity into fat cell triglyceride showed a slight age-related increase under basal conditions as well as on insulin stimulation. It is concluded that at the cellular level it is the triglyceride saturation of fat cells which constitutes the endogenous regulatory factor responsible for the impaired biological action exerted by insulin on the enlarged fat cells in obesity.

Carbohydrate metabolism in various types of hyperlipoproteinaemia.

Insulin secretion has been studied after an oral glucose load in 81 patients with primary hyperlipoproteinaemia and 15 control sugjects. Glucose tolerance was reduced mainly in Type IV, and to a lesser extent in Type IIB hyperlipoproteinaemia. Insulin secretory response to glucose was reduced in Type V and heterogeneous in Type IV hyperlipoproteinaemia. No correlation was found between the triglyceride level and the rate of insulin secretion.

Effect of methandrostenolone on serum triglyceride and cholesterol levels in diabetic patients.

Eighteen adult diabetic patients were treated with methandrostenolone in daily doses of 15 mg for 3 weeks. Serum triglyceride and cholesterol levels and lipoprotein lipase activity were determined before and after treatment. In patients with intense hypertriglyceridaemia, triglyceride concentration decreased and, with the exception of a single patient, lipoprotein lipase activity returned to normal. Cholesterol concentration did not change characteristically.