Biomedical subjects

A Andersson

Publications and source records attributed to A Andersson.

At least 19 recordsLinked to original sources

PubMed1992

Effects of EGF-dextran-tyrosine-131I conjugates on the clonogenic survival of cultured glioma cells.

Epidermal growth factor, EGF, and 131I or 125I-labelled tyrosine were conjugated to the sugar polymer dextran. The conjugates bound to EGF-receptor rich human glioma cells in culture and the binding was mainly receptor specific because cells presaturated with nonradioactive EGF gave strongly reduced binding. The 131I labelled conjugates were used in tests on cellular retention and therapeutical effects. 131I activity delivered to the cells as EGF-dextran-tyrosine-131I remained cell-associated for much longer periods of time than 131I activity delivered by only EGF. The amount of cell-associated 131I activity was nearly constant for up to 25 hours. The 131I labelled conjugate gave, after a one hour incubation period for binding followed by a 25 hour incubation in nonradioactive medium, a good therapeutical effect. This effect, which corresponded to about 3.0 Gy of external 60Co radiation, was due to the specifically bound 131I. The comparatively small effects of nonbound 131I in the culture medium, present only during the first incubation hour, were measured in control experiments with presaturated receptors and were corrected for in the evaluation of the EGF-receptor mediated effects. Control experiments showed that neither nonradioactive EGF nor non-radioactive EGF-dextran conjugates gave measurable effects on clonogenic growth. The results obtained were promising and the possibilities to use EGF-dextran conjugates for therapy should be further examined.

Brain Neoplasms↗

PubMed1992

Expression of the 64 kDa/glutamic acid decarboxylase rat islet cell autoantigen is influenced by the rate of insulin secretion.

This study examined the relationship between insulin secretion and expression of the 64 kDa/glutamic acid decarboxylase autoantigen in pancreatic islets. Islets isolated from Wistar rats were cultured for 3 days under different conditions: in 5.5 mmol/l glucose with or without alpha-ketoisocaproic acid or glipizide and in 28 mmol/l glucose with or without diazoxide. The 64 kDa/glutamic acid decarboxylase autoantigen was precipitated from lysates of [35S]-methionine-labelled islets with sera from patients with Type 1 (insulin-dependent) diabetes mellitus and identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and fluorography. In parallel, insulin contents of the islets and the media were determined as well as the rates of glucose-stimulated (pro)insulin biosynthesis. alpha-Ketoisocaproic acid and glipizide were found to stimulate the expression of the 64 kDa/glutamic acid decarboxylase autoantigen and also the rate of insulin secretion. Diazoxide on the other hand reduced the rate of the 64 kDa/glutamic acid decarboxylase autoantigen synthesis in parallel with an inhibition of glucose-stimulated insulin release. Under most of the conditions employed, (pro)insulin biosynthesis was not affected. The correlation found between the rate of insulin release and expression of the 64 kDa/glutamic acid decarboxylase autoantigen might provide an explanation for the earlier observed relationship between the functional demands on the Beta cells and their rate of destruction which may result in diabetes.

Animals↗

PubMed1992

Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma.

The mechanism by which oral oestrogen-containing contraceptives in women and oestrogen treatment of prostatic carcinoma in men increases the risk of vascular disease is unclear. These agents decrease serum concentrations of vitamin B12, pyridoxal 5-phosphate, and folate, all of which are essential for the metabolism of the atherogenic amino acid homocysteine. We found serum vitamin B12 concentrations to be lower in 17 women using oral contraceptives (219 +/- 84 pmol l-1) than in 13 age-matched female controls (385 +/- 129, p less than 0.001), but similar values were obtained in the two groups both for fasting plasma homocysteine concentrations (9.1 +/- 2.4 vs 9.2 +/- 3.6 mumol l-1) and for the increase in these concentrations after methionine loading (19.2 +/- 7.5 vs 17.8 +/- 5.2 mumol l-1). In five men with prostatic carcinoma, high-dose oestrogen treatment decreased serum vitamin B12 concentrations by a mean of 30% (p less than 0.05) within 4 weeks, during which fasting plasma homocysteine concentrations decreased (13.8 +/- 4.5 vs 10.5 +/- 2.8 mumol l-1) and response to methionine loading increased (12.4 +/- 3.4 vs 17.3 +/- 5.1 mumol l-1), though the latter changes were non-significant. Our findings do not support the hypothesis that hyperhomocysteinemia explains cardiovascular risk in women using oral oestrogen-containing contraceptives, or in oestrogen-treated men with prostatic carcinoma.

Adolescent↗

PubMed1992

Injection of xenogeneic endocrine pancreatic tissue into the portal vein--effects on coagulation, liver function, and hepatic hemodynamics. A study in the pig-to-dog model.

The safety of injecting discordant xenogeneic fetal endocrine pancreatic tissue into the portal vein was studied in a pig-to-dog system. It was found that minced fetal porcine pancreas and fetal porcine isletlike cell clusters prepared by collagenase digestion and culture could be injected with only minor or no hepatic hemodynamic disturbances. Coagulation studies revealed a small increase in plasma fibrinopeptide A, but this increase could be prevented by heparinization of the recipient. There was no consumption of fibrinogen or platelets. In contrast, injection of minced adult porcine pancreas caused pronounced hepatic hemodynamic changes and marked coagulation abnormalities, indicating consumption coagulopathy. The present finding that fetal porcine pancreas can be injected intraportally without deleterious effects in dogs provides a foundation for the eventual clinical use of such material as treatment for insulin-dependent diabetes mellitus.

Animals↗

PubMed1992

Pancreatic islet blood flow after syngeneic pancreaticoduodenal transplantation in rats. Differences between the blood perfusion of the native and the transplanted gland.

Inbred male Sprague-Dawley rats were transplanted with syngeneic pancreaticoduodenal grafts. Diabetes was induced in some of the recipient animals by an i.v. injection of streptozotocin one week before transplantation, while the remaining control rats were untreated, and thus had both an intact native and a transplanted pancreas. The left kidney of the recipient was removed and its blood vessels were used for the graft vascular anastomosis. The graft duodenum was sutured end-to-side to the ileum of the recipient. Two weeks after transplantation the rates of blood flow through both the native and transplanted pancreas and duodenum were measured. The blood perfusion of the whole pancreas and the islets was higher in the tx than in the native gland, although no difference was seen with regard to the duodenum. Administration of glucose to control animals had no effect on either native or tx whole pancreatic or intestinal blood flow. However, the islet blood flow through the native pancreas was increased in response to glucose, while that of the tx gland remained unchanged. The combined data show that the blood flow of a tx pancreas is slightly higher than that of the native organ, and that the response of the islet blood perfusion to glucose administration differs between the native and tx pancreas. This suggests that islets in the tx pancreas 14 days after transplantation are not subject to the same blood flow regulatory mechanisms as native islets.

Animals↗

PubMed1992

Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status.

Homocysteine is a probably atherogenic amino acid, the fasting and post-methionine load serum concentrations of which have been reported to be much lower in premenopausal women than in men and postmenopausal women. This difference has been proposed to explain the reduced proneness of premenopausal women to vascular disease. We measured both free and total plasma homocysteine concentrations both fasting and post-methionine load, in 169 healthy subjects. Twelve subjects (7%) had distinctly abnormal plasma homocysteine values. Among the remaining 157 subjects, neither fasting nor post-load values of free or total homocysteine were lower in premenopausal women (n = 46) than in men of similar age (n = 41) or postmenopausal women (n = 37). Fasting but not post-load values were lower in postmenopausal women than in men of similar age (n = 33), and lower among the women as a whole (n = 83) than among the men (n = 74). In men, fasting values increased with age, and paralleled age-related decreases in the concentrations of homocysteine metabolism cofactors (serum vitamin B12, blood folate, and plasma pyridoxal 5-phosphate). Both in men and in women, fasting total plasma homocysteine values were significantly and negatively correlated to serum vitamin B12 and blood folate concentrations. Whether the small differences in plasma homocysteine values between the present men and women may be a contributory factor vis-à-vis their different proneness to vascular disease has yet to be settled.

Adult↗

PubMed1992

Age stability of human brain 5-HT terminals studied with [3H]paroxetine binding.

The effect of age on serotonin uptake sites labeled with [3H]paroxetine was studied in two sets of brains. The first set included 28 subjects (19 males and 9 females) between the ages 0 and 100 years. The cortex of cingulate gyrus and the amygdala were studied. No age-related changes in binding capacity (Bmax) or binding affinity (Kd) were noted. In the second set, the frontal cortex and hypothalamus from 22 subjects (18 males and 4 females) between 16 and 75 years were studied. No age-related changes in the binding were observed. The interval between death and freezing of the tissue did not influence the binding. Regarding the [3H]paroxetine binding as an indirect marker for 5-HT terminals, the data suggest a stability of 5-HT terminals with increasing age in the human brain.

Adolescent↗

PubMed1992

Glucose regulation of the autoantigen GAD65 in human pancreatic islets.

Recent data suggest that the enzyme glutamic acid decarboxylase (GAD) may be a primary beta-cell antigen involved in the autoimmune response leading to insulin dependent diabetes mellitus (IDDM). Following three days culture of human islets at different glucose concentrations (5.6, 11 or 28 mM), there was a single 65 kDa/GAD band in the islet extracts, as assessed by immunoprecipitation both with serum from a newly diagnosed IDDM patient and a sheep anti-GAD serum. The synthesis of GAD was strongly stimulated at the higher glucose concentrations. Likewise, Western blot analysis indicated a glucose-induced increase of GAD in the islets. The data suggest that an enhanced function of human islet cells increases expression of GAD65. Possibly, this could exacerbate the autoimmune assault in the early stages of IDDM, and be of practical importance in attempts to ameliorate the autoimmune response towards the beta-cells in IDDM.

Autoantigens↗

PubMed1992

Reinnervation of syngeneic mouse pancreatic islets transplanted into renal subcapsular space.

A syngeneic transplantation of 150 islets into the subcapsular renal space was performed on normoglycemic or alloxan-induced diabetic male C57BL/6 mice. Six, 8, 14, or 20-21 wk after transplantation, the graft-bearing kidney was removed and processed for microscopical examinations with indirect immunofluorescence for neuropeptides and tyrosine hydroxylase, and with acetylcholinesterase staining to visualize nerve fibers within the graft. Six weeks after implantation, only a few scattered nerve fibers were observed within the grafts. A progressive increase in the number of nerves was observed until 14 wk after transplantation, after which, a stable level was reached. Alloxan-induced diabetic mice showed quantitatively and qualitatively similar reinnervation to normoglycemic mice 20 wk after transplantation. The findings demonstrate the presence of sympathetic nerve fibers (containing tyrosine hydroxylase and neuropeptide Y), mainly accompanying ingrowing blood vessels; parasympathetic nerve fibers (containing acetylcholinesterase and vasoactive intestinal peptide), possibly reaching the graft from the adjacent renal capsule; and afferent nerve fibers (containing substance P and calcitonin gene-related peptide), which were less numerous. The data suggest that transplanted islets become reinnervated by ingrowth of nerve fibers from the implantation organ and that several types of nerves are present.

Animals↗

PubMed1992

Decreased serum homocysteine in pregnancy.

Total serum homocysteine was found to be significantly decreased in the first trimester of pregnancy, became maximal in the second trimester (about 50% compared with non-pregnant women), whereafter the concentration remained stable throughout the remainder of pregnancy. A return to normal concentrations was seen within 2-4 days post partum. Possible reasons for the decrease of serum homocysteine in pregnancy could be haemodilution and increased remethylation of homocysteine due to increased demands for methionine by the foetus.

Adult↗

PubMed1992