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Biomedical subjects

J H Helderman

Publications and source records attributed to J H Helderman.

At least 73 records · Page 4Linked to original sources
PubMed1988

Antecedent chronic hyperglycaemia blocks phlorizin-induced insulin resistance in the dog.

Hyperglycaemia may enhance insulin resistance typical of non-insulin dependent diabetes mellitus, as well as insulin dependent diabetes mellitus, and thus initiate a vicious pathogenetic cycle. We sought to test the hypothesis that reduction in chronic hyperglycaemia in the diabetic dog by methods that do not employ insulin may improve insulin resistance. We used the glucuretic agent phlorizin in dogs rendered chronically hyperglycaemic and diabetic by alloxan treatment. To analyse glucose disposition the euglycaemic clamp was performed. To minimize the role of counterregulatory influences that might be at play when glucose is reduced, the hyperglycaemic clamp with continuous somatostatin infusion was performed. Although phlorizin normalised plasma glucose in the diabetic dog and reduced plasma glucose in normal, non-diabetic dogs, insulin dependent glucose disposition rate did not improve. While phlorizin itself was associated with insulin resistance in the normal animals, the insulin resistance of diabetes mellitus was not further augmented. We conclude that phlorizin is associated with insulin resistance perhaps by a common pathway shared by chronic hyperglycaemia. Care must be taken when phlorizin is used as an agent to study glucose disposition.

Animals↗
PubMed1988

Relationship between lipoprotein levels and in vivo insulin action in normal young white men.

In epidemiologic studies, hyperinsulinemia has been found to be an independent risk factor for coronary heart disease (CHD). However, the mechanisms responsible for its role in atherogenesis remain unclear. We studied the relationship of in vivo insulin action and plasma lipids and lipoproteins in 44 normotriglyceridemic white men (aged 18 to 34 years). The euglycemic, hyperinsulinemic glucose clamp technique was used to quantitate insulin-mediated glucose disposal (M/I value) at a plasma insulin concentration of approximately 100 microU/mL. The M/I value correlated negatively with plasma triglycerides (r = -0.553, P less than .0001), as well as with fasting plasma insulin levels (r = -0.483, P less than .001), independent of age, body mass index, and fasting plasma glucose levels. A negative correlation of the M/I value was also observed with very low density lipoprotein (VLDL)-cholesterol (r = -0.347, P less than .05), VLDL-triglycerides (r = -0.474, P less than 0.005), and total cholesterol/high density lipoprotein (HDL)-cholesterol ratio (r = -0.431, P less than .01). The relationship between the M/I value and the total cholesterol/HDL-cholesterol ratio was independent of VLDL-cholesterol and VLDL-triglycerides, however, not independent of plasma triglycerides. No relationship was observed between insulin-mediated glucose uptake and total cholesterol, low density lipoprotein (LDL)-cholesterol, and HDL-cholesterol values. Individual differences in plasma triglycerides, fasting insulin concentration, and the total cholesterol/HDL-cholesterol ratio accounted for about half the variance observed in the M/I value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Enhancement of allo-responsiveness of human lymphocytes by acemannan (Carrisyn).

Healing powers have been imputed as being a feature of the gel from the aloe vera plant for centuries. The recent isolation of the active ingredient, acemannan, has made testing of this drug important. Since the drug appears to enhance monocyte function in other experiments, these studies were designed to test the capacity of acemannan to enhance immune response to alloantigen and to test whether the potential enhancement is a monocyte driven phenomenon. Acemannan did not enhance lymphocyte response to syngeneic antigens in the mixed lymphocyte culture (MLC) but importantly increased alloantigenic response in a dose-response fashion (2.6 x 10(-7) - 2.6 x 10(-9)M). This effect of acemannan was shown to be a specific response and to concur with concentrations of in vitro acemannan achievable in vivo. A separate series of mixing experiments demonstrated that acemannan incubation with monocytes permitted monocyte driven signals to enhance T-cell response to lectin. It is concluded that acemannan, the active ingredient of the aloe vera plant, is an important immunoenhancer in that it increases lymphocyte response to alloantigen. It is suggested that the mechanism involves enhancement of monocyte release of IL-I under the aegis of alloantigen. This mechanism may explain in part the recently observed capacity of acemannan to abrogate viral infections in animal and man.

Adjuvants, Immunologic↗
PubMed1988

The use of monoclonal antibodies in fine needle aspiration biopsy of the renal transplant.

This report deals with the clinical application of monoclonal antibody techniques to fine needle aspiration biopsy (FNAB) of the renal transplant. The technique was deemed to be quite helpful in corroborating cell type analysis made by classical cytochemistry (Giemsa staining), and determination of the nature of the lymphoid subset at play in rejection. The role of activation marker analysis and class 2 alloantigen analysis in particular for rejection was also discussed.

Antibodies, Monoclonal↗
PubMed1988

Confirmation of the utility of fine needle aspiration biopsy of the renal allograft.

Allograft immunobiologic theory would predict that analysis of immunocompetent cells infiltrating the renal transplant would be most instructive. Recently a new aspiration biopsy technique has been developed to permit such analysis in patients which can be safely and repetitively performed. The clinical utility of such a technique has been tested utilizing a randomized prospective trial in which an aspirate was obtained every other day from the third post-operative day until discharge. Analysis included examination of adequacy criteria and the capacity of pathologic diagnosis to corroborate clinical diagnosis from coded specimens. Ninety-six aspirates from 21 consenting transplant recipients were obtained and analyzed. In 94 instances a clinical diagnosis could be made; 80 aspirates fulfilled adequacy criteria. We found the technique to be highly sensitive (greater than or equal to 90%) and highly specific (greater than or equal to 90%) for the clinical diagnoses of acute allograft rejection, post-operative acute renal failure, cyclosporine toxicity, and normal function. We conclude that the fine needle aspiration technique is an important adjunct to analysis of clinical renal transplantation and offers a major advantage to the clinical scholar in understanding transplant biology.

Acute Kidney Injury↗
PubMed1988

Severe diabetes induced in subtotally depancreatized dogs by sustained hyperglycemia.

Chronic clamping of plasma glucose levels at greater than or equal to 250 mg/dl in four partially depancreatized but previously nondiabetic dogs was followed within 2 wk by persistent hyperglycemia and glycosuria of less than or equal to 500 g/day, ketonuria, and weight loss. Three of the four dogs required daily insulin injections to control these catabolic manifestations. There was no evidence of spontaneous improvement of the severe diabetic state during the 39-69 days of observation after discontinuation of intravenous glucose infusion. Impairment of intravenous glucose tolerance, loss of the insulin response to glucose and arginine, fasting hyperglucagonemia, exaggerated glucagon responsiveness to arginine, and a significant reduction in sensitivity to insulin were characteristic of all diabetic dogs. Morphometric analysis of the endocrine pancreas revealed a profound reduction in the number and size of identifiable islets of the hyperglycemic dogs compared with islets from their own pancreases resected months earlier and with those from pancreatic remnants of eight subtotally depancreatized control dogs that had not been subjected to chronic hyperglycemic clamping. The reduction in number and size of islets of the hyperglycemic dogs was largely the consequence of depletion of insulin-containing cells and was similar to that of dogs with long-standing alloxan-induced diabetes. In the eight control dogs, clinical evidence of diabetes did not develop during a follow-up period of 193-296 days. In this group, there was no evidence of diminution of intravenous glucose tolerance, of the insulin response to glucose or arginine, or of insulin sensitivity as determined by an acute hyperinsulinemic hyperglycemic clamp. The number and size of islets and number of beta-cells in pancreatic remnants from these dogs did not differ morphometrically from those of the pancreatic segment that had been resected. We conclude that in subtotally depancreatized but nondiabetic dogs, maintenance of constant hyperglycemia of greater than or equal to 250 mg/dl by means of intravenous glucose infusion causes a severe, persistent, and often insulin-requiring diabetic state that does not occur in the absence of the hyperglycemia.

Animals↗
PubMed1987

Kidney transplant recipients with long incubation-positive antiglobulin-negative T cell crossmatches.

Low-affinity, cold-reactive antibodies easily removed by washing were not detected by the antiglobulin technique but killed T lymphocytes when washing was omitted, incubation was prolonged, and cytotoxic tests were incubated at room temperature or at 4 degrees C. These antibodies were present in approximately 25% of sera from dialysis patients. Only a subset of such sera (22%) reacted with autologous lymphocytes. The majority (86%) appeared to detect non-HLA antigens. A small number (14%) detected class I HLA antigens. Two patients transplanted with antiglobulin-negative, T-warm-negative crossmatch results, but positive cytotoxicity after a 2-hr incubation without washing, rapidly lost their grafts (less than 1 month) due to rejection. Their sera contained antibodies against non-HLA alloantigens expressed on lymphocytes and platelets, but not on granulocytes or erythrocytes. Two other patients with positive autoantibody tests exhibiting similar crossmatches with the current serum were transplanted recently. Both of them retain their grafts with good function at one month. In two other cases, the recipients were unreactive against the donor in current serum but displayed an antiglobulin-negative, 2-hr cytotoxicity-positive pattern in a previously drawn serum specimen. One patient continues to have stable renal function after 10 months. The other patient lost the transplant as a result of renal artery thrombus thought not to be immunologic in origin. Work is continuing to define the specificity and determine the clinical relevance of such cold-reactive antibodies.

Autoantibodies↗
PubMed1987

Monocyte-T lymphocyte interaction for regulation of insulin receptors of the activated T lymphocyte.

During activation the lymphocyte attains functional insulin receptors with precise regulation, a consequence of insulin concentration manipulations. These studies test the hypothesis that insulin receptor (+) monocytes monitor insulin concentrations, so instructing the T lymphocytes. Monocyte-enriched populations were incubated with insulin (0-10(-6) M) followed by co-culture with T lymphocytes and an activating stimulus. A dose-related fall in T lymphocyte insulin receptor binding was observed that was specific for the monocyte as the signalling cell and for insulin as the signal received. Monocytes from normal volunteers during a euglycemic, hyperinsulinemic clamp were cultured with T lymphocytes and an activating stimulus. A decline in specific insulin receptor binding on T lymphocytes was observed, which Scatchard analysis demonstrated to be a consequence of reduction in receptor numbers. These studies demonstrate that the receptor (+) monocyte perceives the concentration of insulin and passes this information to T lymphocytes regulating the number of activation-induced insulin receptors. The interplay between the monocyte and T lymphocyte parallels the interaction of these cell types for recognition of antigen.

Animals↗
PubMed1986

Chronic sclerosing glomerulopathy (heroin-associated nephropathy) in intravenous T's and Blues abusers.

The intravenous (IV) use of pentazocine (Talwin) and tripelennamine (pyribenzamine) has become a major form of drug abuse seen in the midwestern United States. Complications of this abuse have included psychotic reactions, acute pulmonary insufficiency, convulsions, and various infections. We have observed three patients in whom the IV use of these agents was associated with the nephrotic syndrome and renal histopathologic findings similar to that reported in heroin addicts with the so-called "heroin-associated nephropathy." Percutaneous renal biopsy demonstrated focal to diffuse segmental or global glomerulosclerosis by light microscopy. Electron microscopy revealed glomerular visceral epithelial cell foot process effacement and microvillus formation. Immunofluorescent studies were negative in the two patients studied. One patient presented in renal failure, and two others progressed to renal failure within 3 years of diagnosis. We suggest the term opiate nephropathy for this lesion in narcotics users, indicating its potential occurrence in non-heroin-using drug addicts.

Adult↗
PubMed1986

Simulation of the normal glucopenia-induced decline in insulin partially restores the glucagon response to glucopenia in isolated perfused pancreata of streptozotocin-diabetic rats.

To determine if the loss of the glucagon response to glucopenia that follows destruction of beta cells is at least in part a consequence of the absence of the normal glucopenia-induced decline in insulin secretion, pancreata from insulin-requiring streptozotocin-diabetic rats were studied. In the absence of insulin, a reduction in perfusate glucose concentration from 150 to 25 mg/dl failed to elicit a rise in glucagon concentration. When insulin was co-perfused at 30 mU/ml, the estimated within-islet concentration of insulin under these circumstances, but discontinued during the glucopenic interval, reducing the insulin concentration in the pancreatic venous effluent from approximately 26 mU/ml to less than 100 microU/ml, a prompt and significant rise in glucagon was observed until glucose and insulin levels were raised to their original concentrations. The rise in glucagon, which was approximately 25% of the normal response, did not occur when insulin concentration in the perfusate was maintained at 30 mU/ml during the glucopenic period. Nor did it occur when insulin was perfused at 360 microU/ml and discontinued during the glucopenic period, thereby lowering insulin in the venous effluent from 300 microU/ml to 5 microU/ml. It is concluded that the decline in insulin from its normal concentrations within the islets makes a modest but significant contribution to the rise in glucagon that occurs during glucopenia.

Animals↗
PubMed1985

A controlled study of cellular immune function in affective disorders before and during somatic therapy.

Lymphocyte blastogenesis induced by lectins (PHA, Con A, and PWM) was assessed in 27 drug-free patients with unipolar (n = 21) or bipolar (n = 5) depression and 13 normal controls. Fifteen patients were restudied after clinical remission. Symptomatic patients did not differ from controls nor did endogenous and nonendogenous depressions differ in their lymphocyte blastogenesis response to any of the three lectins. However, a significant reduction in lymphocyte blastogenesis with both PHA and Con A stimulation was found following somatic treatment. Cellular immune function appears to be normal in depressed patients, although the somatic therapies are associated with a reduction in this function.

Adult↗
PubMed1985

Disturbances in mineral metabolism after successful renal transplantation.

Abnormalities of mineral metabolism remain a clinical problem after successful renal transplantation. These disturbances may be the result of derangements in divalent ion, parathyroid hormone (PTH) and/or vitamin D metabolism. We therefore measured serum Ca, phosphorus, PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels and fractional intestinal Ca absorption (alpha) in 6 patients before and after successful transplantation (early, less than or equal to 6 months). 3 were reexamined later (late, greater than or equal to 24 months after transplantation). The patients exhibited decreased serum levels of 1,25(OH)2D and alpha before the renal transplantation. In the early stages, renal transplantation reduced serum phosphorus from 5.55 +/- (SD)1.96 to 2.96 +/- 0.95 mg/dl (p less than 0.02); this was accompanied by a rise in serum 1,25(OH)2D from 8.7 +/- 1.5 to 26.3 +/- 8.4 pg/ml (p less than 0.005). The calcemic response to PTH infusion became normal, since the increment in serum Ca rose from 0.45 +/- 0.21 mg/dl before transplantation to 1.03 +/- 0.18 mg/dl early after transplantation. Although the mean value for alpha increase significantly from 0.263 +/- 0.048 to 0.402 +/- 0.175 (p less than 0.05), alpha was subnormal in 3 patients (alpha less than 0.37). Urinary Ca was high in 3 patients, and it exceeded absorbed Ca (from intestines) in 4 patients (indicative of negative Ca balance). Serum PTH fell significantly but remained above normal. It was hoped that late after transplantation, when patients were maintained on smaller doses of oral glucocorticoids, these abnormalities would be ameliorated. However, hypercalciuria was found in 2 of 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗