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Biomedical subjects

D Barzilai

Publications and source records attributed to D Barzilai.

At least 19 recordsLinked to original sources

Bone turnover in cortical and trabecular bone in normal women and in women with osteoporosis.

UNLABELLED: This study is based on the assumption that is bone turnover, shown by the uptake of 99mTc-MDP, indicates a high rate of bone loss in patients with osteoporosis, it could potentially predict bone loss in patients at risk before significant bone loss has occurred. METHODS: Quantitative bone SPECT (QBS) using 99mTc-MDP, expressed as the %ID/cc x 10(-3), was performed in 71 women who had osteoporosis in the lumbar vertebrae, the femoral neck or both, and in 54 age-matched normal female controls. Of the women with osteoporosis, 42 had postmenopausal osteoporosis and 29 had primary hyperparathyroidism (HPT) and osteoporosis. RESULTS: QBS increased with age in the cortical bone and decreased in the trabecular bone of the normal women. Quantitative bone SPECT in the femoral neck was 3.18 +/- 1.20 and was 2.73 +/- 1.06 in the femoral shaft in 20 women with postmenopausal osteoporosis of the femoral neck. In 19 women with HPT and osteoporosis of the femoral neck, the QBS value in the femoral neck was 3.57 +/- 0.92 and in the femoral shaft 3.38 +/- 1.12. These values were also significantly higher for the femoral neck and for the femoral shaft than those of normals. Although QBS values were higher in the lumbar region in 39 women with postmenopausal osteoporosis (4.59 +/- 1.45) and in 27 women with HPT (4.30 +/- 1.52), as compared with the normal group (4.28 +/- 1.61), the difference was not statistically significant. CONCLUSION: This study shows that bone turnover is significantly higher in the cortical bone of women with osteoporosis than in normal women.

Bone Density

Correlation between glucose disposal and amino acids levels in hyperthyroidism.

Insulin is known to decrease plasma levels of both glucose and amino acids. We have designed a study to examine whether in hyperthyroidism, where insulin sensitivity is changed, correlation between glucose disposal and amino acids levels is maintained. We studied 5 normal (N) and 5 hyperthyroid (HTD) subjects, and measured glucose disposal rate and serum levels of plasma amino acids before and during insulin infusion utilizing the euglycemic hyperinsulinemic clamp technique. Insulin was effective in decreasing the levels of all amino acids in the plasma of all subjects. The mean amino acid decrease in response to insulin infusion rate of 10 mu/kg/min was 35 +/- 3% in N and 50 +/- 3% in HTD. The half maximally effective dose of insulin on glucose disposal was 43 +/- 3 and 69 +/- 9 uU/ml in N and HTD respectively (p < 0.05). The half maximally effective dose of insulin on decreasing plasma amino acids was 37 +/- 7 and 75 +/- 5 uU/ml in N and HTD respectively (p < 0.01). The concentration of insulin giving a half maximal effect on serum amino acids correlated with the half-maximally effective dose on glucose disposal rate (r = 0.72, p < 0.01). The maximal effect on total amino acid levels correlated with maximal glucose disposal (r = 0.76, p < 0.001). Similar results were observed with branched chain amino acids. We conclude that in hyperthyroidism glucose disposal and decrease in amino acids levels are closely correlated as in healthy subjects. This also confirms the association between glucose disposal and amino acids levels in a variety of insulin sensitive and resistant states.

Adult

Frequent induction of insulin autoantibodies by D-penicillamine in patients with rheumatoid arthritis.

D-Penicillamine is a drug known to induce various immunological abnormalities. We used a competitive radiobinding assay, to evaluate the presence of insulin autoantibodies in 42 patients with rheumatoid arthritis (RA), under various treatment modalities. In 11/42 (26.2%) patients, the levels of insulin autoantibodies (range 59-1970 nU/ml) exceeded our upper limit of normal range (50 nU/ml). Nine of these 11 (81.8%) insulin autoantibodies positive patients had been treated with D-penicillamine. Out of 21 D-penicillamine treated patients, 9 (42.9%) were insulin autoantibodies positive (range 80 to 1970 nU/ml). An inverse correlation was found between the concentration of insulin autoantibodies and the time interval since the last drug administration, R = -0.58 (p < 0.05). No correlation was found between the autoantibodies levels and age, or duration of D-penicillamine treatment. In summary, elevated concentration of serum insulin autoantibodies are most probably induced by D-penicillamine therapy in patients with RA and tend to decrease after the drug withdrawal.

Adult

Effect of wheat germ agglutinin and concanavalin A on insulin binding and response by Madin-Darby canine kidney cells.

In Madin-Darby canine kidney (MDCK) cells, specific plasma membrane binding of [125I]insulin was undetectable. Correspondingly, neither insulin-stimulated incorporation of [14C]glucose into glycogen nor insulin-induced uptake of radiolabeled alpha-aminoisobutyrate ([ 3H]AIB) could be demonstrated. These results suggested that MDCK cells lack specific cell surface insulin receptors. To further examine this question intact MDCK cells were preincubated with antireceptor serum and subsequently labeled with [125I]protein A; however, insulin receptors were not detected. Control H4 hepatoma cells bound insulin, responded with increased glycogen synthesis and amino acid uptake, and possessed immunologically recognizable insulin receptor components. The insulin-associated response of stimulated [3H]AIB uptake was induced in MDCK cells by the insulinomimetic lectins concanavalin A (130-140% of basal value at concentrations of 10-40 micrograms/ml) and wheat germ agglutinin (140-160% of basal value at concentrations of 10-30 micrograms/ml). This stimulation was abolished by the respective lectin-specific monosaccharides D-mannose and N-acetyl-D-glucosamine. Together, these data indicate that the insulin-like activity of concanavalin A and wheat germ agglutinin can be elicited in MDCK cells even in the apparent absence of specific plasma membrane insulin-binding sites.

Aminoisobutyric Acids

Digoxin-like immunoreactive factor(s) in human gonadotropin stimulated follicular fluid.

Plasma digoxin-like immunoreactive factor(s) (DLIF) have been reported in various pathophysiological conditions associated with volume expansion and linked to the regulation of blood volume and pressure. We hypothesized that DLIF might be present in rapidly expanding gonadotropin-stimulated ovarian follicles. The mean total and free DLIF concentrations in the follicles (n = 9) studied were 4925 nmol/L and 1885 nmol/L, respectively. These concentrations were substantially higher than the plasma total and free DLIF levels in these women: 1216 nmol/L and 158 nmol/L, respectively (p less than 0.0001). The plasma DLIF levels in the gonadotropin-treated women were comparable to those in term pregnant women, which are known to be higher than those in non-pregnant women. The ovary thus may be a source of DLIF in the plasma of gonadotropin-treated women, and DLIF may have a role in ovarian follicular fluid homeostasis.

Blood Proteins

Difficult preoperative diagnosis of a patient with sclerosing splenic hemangioma.

We present a young asymptomatic woman with splenomegaly and a large isolated splenic mass demonstrated by ultrasonography, 99mTc sulfur colloid, and gallium scintigraphy studies. Computerized tomography (CT) and three-phase 99mTc-labeled red blood cell imaging suggested a malignant lesion. Repeated sonographically guided fine needle aspiration (FNA) obtained only blood, suggesting the possible vascular nature of the tumor. Splenectomy established the diagnosis of splenic hemangioma (SH) with marked sclerotic changes. We conclude from this case that 1) the sclerotic and cystic changes in the SH and the abdominal lymphadenopathy could explain why the three-phase red blood cell and CT scanning, respectively, suggested that the lesion was malignant rather than benign; 2) guided FNA of a splenic mass suspected to be hemangioma may be an additional safe and useful diagnostic procedure. Multiple aspirations yielding blood alone suggest hemangioma and may prevent an unnecessary operation. To the best of our knowledge, this is the first reported case in the literature of FNA of splenic hemangioma.

Adult

Talcosis presenting as pulmonary infiltrates in an HIV-positive heroin addict.

A case of an HIV-positive young drug addict presenting with fever, respiratory distress, and pulmonary infiltrates is reported. Pulmonary talcosis was diagnosed by transbronchial biopsy. The differential diagnosis of pulmonary infiltrates in HIV-positive patients is reviewed and the predisposition of drug addicts to develop both HIV infection, as well as pulmonary talcosis, is discussed. Pulmonary talcosis must be considered in the differential diagnosis of pulmonary infiltrates of HIV-positive drug addicts.

Adult

Calmodulin inhibitors and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate do not prevent the inhibitory effect of prostaglandin F2 alpha on cyclic AMP production in isolated rat corpora lutea.

In the rat corpus luteum, prostaglandin F2 alpha (PGF2 alpha) rapidly inhibits LH-induced cyclic AMP (cAMP) production when given in vivo or to isolated corpora lutea, but not to broken-cell preparations. The suggestion that increased cytosolic calcium concentration mediates PGF2 alpha action was investigated in corpora lutea of pseudopregnancy induced in immature rats by administration of pregnant mare serum gonadotrophin (15 i.u.). Isolated 10-day-old corpora lutea were incubated for 90 min with LH (5 micrograms/ml), PGF2 alpha (10 mumol/l) and other additions, and cAMP concentration in the tissue was estimated. The putative inhibitor of intracellular calcium release or action, 8-(n,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8; 30 or 150 mumol/l), did not abolish the effect of PGF2 alpha. Similarly ineffective was the combination of TMB-8 (150 mumol/l) and calcium-depleted medium (free ionized calcium concentration, 30 nmol/l). Calmodulin inhibitors of three different chemical structures were then tested. The phenothiazine trifluoperazine, at 300 as well as 30 mumol/l, did not interfere with the inhibitory effect of PGF2 alpha on cAMP, while suppressing (at 300 mumol/l) progesterone secretion in LH-treated tissue. Furthermore, inhibition by PGF2 alpha was not impaired by pimozide, a diphenylbutylpiperidine (25 and 50 mumol/l) nor by N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7; 15 and 45 mumol/l). In the presence of LH alone, W-7 (45 mumol/l) inhibited and TMB-8 (30 mumol/l augmented cAMP accumulation, indicating that the luteal tissue was effectively exposed to these compounds. Thus, drugs known to inhibit calcium- and calmodulin-dependent processes in a variety of tissues did not abolish the inhibitory action of PGF2 alpha on luteal cAMP production.

Animals

Inhibition by vanadate of cyclic AMP production in rat corpora lutea incubated in vitro.

Vanadate, a normal constituent of cells, has been reported to affect a variety of enzymes involved in phosphate transfer; the findings regarding adenylate cycle vary with the tissue and experimental system. In the corpus luteum, cyclic AMP (cAMP) stimulates steroidogenesis; and prostaglandin F2 alpha, which induces luteal regression, inhibits luteinizing hormone (LH)-induced cAMP accumulation. We examined the influence of orthovanadate on cAMP concentration in isolated corpora lutea from pseudopregnant rats. With 2 mM vanadate, basal cAMP level was unaffected, but LH-induced cAMP accumulation was inhibited by 45-68%. Lower doses of vanadate (0.2-1 mM) were almost as effective. When added simultaneously with LH, vanadate was inhibitory within 25 min, but no inhibition occurred when vanadate was added for 30 min to tissue pretreated with LH for 60 min. The decrease in cAMP accumulation was observed also when corpora lutea were exposed to vanadate in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM), indicating that vanadate inhibits cAMP synthesis. Vanadate may increase cytosolic calcium by inhibiting ion pumps in cell membranes. Thus, we examined the effect of vanadate in corpora lutea incubated in calcium-depleted medium and found that vanadate still inhibited cAMP formation. Vanadyl sulfate (0.4 and 2 mM) reduced the LH-induced cAMP accumulation as effectively as vanadate. Thus, the use of vanadate as a tool for exploring physiological regulators of luteal adenylate cyclase should be considered.

1-Methyl-3-isobutylxanthine

Natural killer cell activity in post-necrotic cirrhotic patients as related to hepatitis-B virus infection and plasma zinc levels.

In view of the suggested physiological role of natural killer (NK) cells in immunosurveillance and defence against viral infections, we have investigated the relationship between hepatitis B virus (HBV) infection and NK activity against K-562 cells in patients with post-necrotic cirrhosis. Overall, the NK activity in cirrhotic patients did not differ from age- and sex-matched controls. However, cirrhotic males with evidence of HBV infection with or without HBs antigenemia tend to have lower NK activity than controls. Cirrhotic males without evidence of HBV infection do not differ from controls. Such a trend was not observed in the female cirrhotic patients examined. In addition significantly reduced NK activity was observed in cirrhotic patients with low plasma zinc levels. This relationship is of interest because of the known association between zinc deficiency and various immunodeficiencies.

Adolescent

Primary therapy for Cushing's disease with metyrapone.

A 13-year-old boy was diagnosed as suffering from pituitary-dependent Cushing's syndrome. He was treated with 2.0 g of metyrapone daily as the sole treatment for four years. All clinical and biochemical stigmata of Cushing's disease disappeared within a few months. The patient grew 23.0 cm in four years and regained normal health. No significant side effects of metyrapone were noticed. Administering the medication at 2 PM and 8 PM allowed higher cortisol levels in the morning and noon hours than in the evening and night, approximating the normal diurnal variation in cortisol production. We conclude that metyrapone may be considered the sole treatment in patients with Cushing's disease.

Adolescent

The dual effect of calcium on aromatization by cultured human trophoblast.

To study the effect of calcium ion on aromatization of an androgenic precursor to estradiol by the placenta, cultured term trophoblasts were used as a model system. Secretion of estradiol into the culture medium was regarded as indicating aromatization, since cells cultured with no androgenic precursors produced only insignificant amounts of estradiol. EGTA, verapamil and ionophore A23187 inhibited aromatization, while trifluoperazine, an inhibitor of the calcium-calmodulin complex, interfered with the stimulatory effect of cyclic AMP on aromatization. We conclude that calcium ion has an essential role in the aromatization of 4-androstene-3,17-dione to estradiol. The calcium-calmodulin complex is required for activation of aromatase by cyclic AMP. However, when flooded with calcium by ionophore A23187, the trophoblast is unable to effectively buffer calcium, and aromatization is inhibited.

Androstenedione

Correlation between insulin clearance and insulin responsiveness: studies in normal, obese, hyperthyroid, and Cushing's syndrome patients.

Insulin clearance and secretion determine the plasma insulin concentration. To elucidate the significance of these parameters in man, we employed the euglycemic insulin clamp technique to measure insulin sensitivity, insulin responsiveness, and insulin clearance, and we calculated the basal insulin delivery rate. In 27 patients (six normal, six obese, ten hyperthyroid, and five with Cushing's syndrome), insulin was infused at rates of 0.3, 1, 3, or 10 mU/Kg/min, and insulin concentration and glucose utilization were measured. C-peptide concentrations were measured before and during insulin infusion and decreased significantly, indicating a reduction of endogenous insulin secretion to 62% of basal in normals and a similar reduction in the other groups. Maximal responsiveness to insulin was a glucose utilization rate of 450 +/- 20 mg/min/m2 in normals, unchanged in obese, 42% increased in hyperthyroid, and 34% decreased in Cushing's syndrome patients. Sensitivity to insulin was decreased in all three abnormal groups. Insulin clearance rates were 1,050 +/- 80 mL/min/m2 for normals, not significantly changed in obese, 45% increased in hyperthyroid, and 33% decreased in Cushing's syndrome patients. All three abnormal groups showed hyperinsulinemia compared to normal. The basal insulin delivery rates were calculated as 7.0 +/- 0.3 mU/min/m2, with a threefold increase in obese and in hyperthyroid and no significant change in Cushing's syndrome patients. Insulin clearance correlated well with insulin responsiveness (r = .65, P less than 0.001), but poorly with insulin sensitivity (r = .36).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult