Search PubMed⌕ Search

Biomedical subjects

L Lazarus

Publications and source records attributed to L Lazarus.

At least 55 records · Page 3Linked to original sources
PubMed1984

Growth hormone binding to cultured human breast cancer cells.

The role of pituitary hormones in the pathogenesis of human breast cancer is unclear, although hypophysectomy is of therapeutic benefit in some patients with advanced breast cancer. Agents that lower serum PRL are of little value in the treatment of breast cancer, suggesting that other pituitary hormones may be important in the control of the growth of human breast cancer in vivo. Since human (h) GH is lactogenic in rodents, we investigated the binding of [125I]hGH and [125I]hPRL to the cultured human breast cancer cell lines T-47D and MCF-7. Both [125I]hGH and [125I]hPRL bound to a saturable binding site with high affinity (Ka = 0.94-1.70 X 10(9) M-1) and low capacity (4140-6560 sites/cells) in the two cell types. hGH and hPRL were mutually competitive, indicating that both hormones bound to the same receptor site. After binding of [125I]hGH to cell monolayers, the hormone was rapidly internalized in a time-, temperature-, and energy-dependent fashion. Lysosomotropic agents inhibited degradation of [125I]hGH and enhanced specific binding. Preincubation of MCF-7 cells with either hGH or hPRL resulted in loss of hGH/hPRL-binding sites, although hGH was consistently more potent in inducing down-regulation of the receptor. On the basis of these observations we suggest that hGH is a potent ligand for the lactogenic receptor in human breast cancer cells in vitro and may be important in the pathogenesis, growth, and metastasis of human breast cancer.

Aged↗
PubMed1984

Correlation of lactogenic receptor concentration in human breast cancer with estrogen receptor concentration.

The presence of receptors for lactogenic hormones in human breast cancer tissue has been documented previously, but the relationship between the expression of these receptors and estrogen receptor (ER) status has not been adequately studied. In this report, the specificity of 125I-human growth hormone (HGH) binding in both cultured human breast cancer cell lines and tumor biopsies was studied to establish that HGH was a suitable ligand for investigating lactogenic receptor concentration in these tissues. In addition, the relationship between specific binding of 125I-HGH and ER concentration in human breast cancer was investigated. Specific 125I-HGH binding to 14 breast cancer cell lines in long term culture and to membrane preparations (microsomal and plasma membrane fractions) from 31 breast cancer biopsy specimens was examined. Human prolactin and HGH were approximately equipotent in inhibiting binding of 125I-HGH to both cultured breast cancer cell lines and to membrane preparations from breast cancer biopsy specimens. Competitive inhibition experiments using lactogenic and somatogenic hormones established that the specificity of 125I-HGH binding to breast cancer biopsy material was similar to that of cultured breast cancer cell lines and similar to that reported for subprimate lactogenic receptors. Saturable, high-affinity (Ka = 0.53 to 2.33 nM-1), low-capacity (330 to 6560 sites/cell) growth hormone binding sites were found on each of the ER-positive cell lines, whereas no specific 125I-HGH binding to ER-negative cell monolayers was detected. When all cell lines were considered, a significant linear correlation (r = 0.745, p less than 0.001) between ER and lactogenic receptor concentrations was found. Significant specific 125I-HGH binding, greater than 1% of the total radioactivity added, was detected in 20 of 31 (65%) breast tumor biopsy specimens. The mean affinity and capacity of the lactogenic receptor as measured in 8 separate membrane preparations were Ka = 0.52 +/- 0.09 (S.E.) nM-1 and 255 +/- 85 fmol/mg protein. Membrane preparations from ER-negative tumors (less than 3 fmol ER/mg cytosol protein) bound significantly less 125I-HGH than did membrane preparations from ER-positive tumor biopsies (1.22 +/- 0.44 versus 3.21 +/- 0.56%, p less than 0.05). A significant linear correlation between specifically bound 125I-HGH and ER concentration (r = 0.412, p less than 0.02) was demonstrated in the 31 breast cancer biopsy specimens studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Binding, Competitive↗
PubMed1983

Failure of insulin infusion during euglycemia to influence endogenous basal insulin secretion.

Despite some evidence of self-regulation of insulin secretion, it is unclear whether endogenous insulin influences insulin secretion independently of blood glucose. The aim of the present study was to examine this question in humans. Seven healthy fasting man were given two-hour porcine insulin infusions (40 mU/min) with and without maintenance of euglycemia (glucose clamp). Intravenous glucose required to maintain basal blood glucose levels (4.2 +/- 0.1 mmole/liter) during insulin infusion was 34.3 +/- 3.0 gm with a mean rate of 273 +/- 29 mg/min in the second hour of insulin infusion. During the glucose clamp, mean C-peptide levels were not significantly altered from fasting levels of 1.91 +/- 0.24 ng/ml, but when blood glucose levels fell by approximately 1 mmole/liter, C-peptide fell to 0.37 +/- 0.07 ng/ml. Plateau insulin levels were significantly higher during euglycemia than during mild hypoglycemia (53.2 +/- 5.6 mU/liter versus 38.5 +/- 3.6 mU/liter, P less than 0.01). Plasma nonesterified fatty acids were suppressed equally in the two studies. However, a rise in plasma glucagon seen during mild hypoglycemia was absent when euglycemia was maintained. We conclude that insulin self-regulation (either direct of neurally mediated) is not physiologically important in the basal state in normal humans and that the blood glucose-insulin feedback loop dominates in the short-term control of basal insulin secretion.

Adult↗
PubMed1983

Comparison of potency of porcine insulin and semisynthetic human insulin at 3 dose levels using the euglycaemic clamp.

The relative potency of porcine insulin and semisynthetic human insulin has been examined in humans using the euglycaemic glucose clamp technique. Three 90 minute consecutive infusions at 2.4, 4.8 and 7.2 units/hr were administered to 7 normal subjects. The rate of glucose infusion (mg/min, mean +/- SEM) required to maintain euglycaemia during the last 40 minutes of each insulin infusion for porcine (P) and human (H) insulin was not significantly different. However, when the glucose infusion rate was expressed as a function of the mean serum insulin level (mU/l) over the same period of time the values for P and H at 4.8 and 7.2 U/hr were not significantly different but H was greater than P (13.6 +/- 1.9, v 10.8 +/- 1.9, p less than .05) at 2.4 U/hr. Mean serum insulin levels did not differ significantly for human or porcine insulin infusion. This study confirms the similarity in potency between human and porcine insulin in the human. However, delivery at 2.4 U/hr, which would predominantly affect hepatic glucose output, suggests that semisynthetic human insulin is more potent than porcine insulin with respect to the liver.

Adult↗
PubMed1983

Characterization of specific growth hormone binding sites in mouse fibroblasts.

The demonstration that mouse embryo mesenchymal cells produce somatomedin-like immunoreactivity suggests that fibroblasts may be a target tissue for GH action. The aim of this study was to investigate the interaction of GH with mouse fibroblasts. Specific binding sites for GH in mouse fibroblasts (BALB/c and Swiss 3T3) have been characterized. Binding of [125I]iodo-human GH (hGH) was rapid, reversible, and time and temperature dependent. Maximal binding was achieved within 2 h at 30 C and was rapidly dissociable at this temperature with or without excess unlabeled hormone. Specific binding of [125I]iodo-hGH was similar over the pH range 6.6-8.2. Half-maximal inhibition of specific binding was obtained with 10 ng/ml hGH. A linear relationship between specific binding and cell number was found and negligible degradation of [125I]iodo-hGH occurred during the binding studies. Somatogenic hormones from various species, including mouse GH, rat GH, porcine GH, and bovine GH competed for binding with [125I]iodo-hGH. Lactogenic hormones did not displace [125I]iodo-hGH at low concentrations. Scatchard analysis revealed curvilinear plots suggesting that [125I]iodo-hGH was binding to two sites. The affinity constants and capacities of these binding sites on BALB/c 3T3 cells were 7.46 X 10(9) M-1 and 4,000 sites per cell and 0.26 X 10(9) M-1 and 67,000 sites per cell. Using [125I]iodo-bovine GH and [125I]iodo-human placental lactogen as labeled ligands two distinct binding sites were found with affinity constants of 6.1 X 10(9) M-1 and 1.1 X 10(9) M-1, respectively. These data are consistent with the presence of cell surface somatogenic and lactogenic receptors in mouse fibroblasts and suggest GH receptors may be present on many cell types not previously considered to be target tissues for GH action. The mouse fibroblast GH receptor may provide a useful model for somatogenic receptors, particularly if it is coupled to somatomedin production as appears to be the case with human fibroblasts.

Animals↗
PubMed1983

Identification and characterization of specific growth hormone receptors in cultured human fibroblasts.

A significant impediment to studies of growth disorders in man has been the lack of an easily accessible target tissue for studies of GH action. As human fibroblasts have been shown to produce a somatomedin-C-like peptide in culture, the aim of this study was to investigate the interaction of GH with cultured fibroblasts. GH binding to human skin fibroblasts and to lung fibroblasts was examined. Specific binding of [125I]iodo human GH [( 125I]iodo hGH) was rapid, reversible, and time and temperature dependent. Maximal binding was achieved within 2 h at 30 C and specifically bound [125I]iodo-hGH was rapidly dissociable at this temperature. A linear relationship between specific binding of [125I]iodo-hGH and cell number was found and negligible degradation of labeled hormone occurred during the binding studies. Half-maximal inhibition of specific binding occurred at 30 ng/ml hGH. Lactogenic and nonprimate somatogenic hormones did not displace [125I]iodo-hGH at the concentrations tested. Scatchard analysis of [125I]iodo-hGH binding to human skin fibroblasts demonstrated a single class of binding sites with an affinity constant of 1.07 +/- 0.07 (SEM, n = 5) X 10(9) M-1 and a capacity of 8355 +/- 1880 site per cell. Similar GH-receptor characteristics were found on each of the fibroblast cell lines examined irrespective of the site of origin (skin or lung) or age of donor. These findings demonstrate for the first time specific GH receptors in cultured human fibroblast cell lines. The demonstration of GH receptors in human fibroblasts should encourage the search for similar receptors in tissues not previously considered to be target tissues for GH action. On the basis of these studies we suggest that cultured skin fibroblasts may be a suitable tissue for the study of GH-receptor status in patients with disorders of growth.

Adult↗
PubMed1979

Acute effects of lithium on central dopamine and serotonin activity reflected by inhibition of prolactin and growth hormone secretion in the rat.

The acute administration of lithium chloride significantly inhibits both prolactin and growth hormone secretion in the rat. In terms of known neuroendocrine relationships this finding indicates that lithium administration alters both dopamine (DA) and serotonin (5-HT) activity in the hypothalamus. The data suggest that DA activity is increased (inhibiting prolactin release) and 5-HT activity is decreased (reducing growth hormone stimulation). The data are in agreement with fluorescent histological studies on the effects of chronic lithium administration and suggest that endocrine parameters may be used to provide neuropharmacological information about compounds which alter brain monoamine activity.

Animals↗
PubMed1979

A simple procedure for the assay of brain biogenic amines by selected-ion monitoring: its application to the elucidation of the mechanism of prolactin release induced by 3-iodo-L-tyrosine.

A simple method for the assay of brain biogenic amines by selected-ion monitoring was applied to examination of the effects of 3-iodo-L-tyrosine on the hypothalamic-median eminence concentrations of dopamine, noradrenaline and serotonin in the rat. Thirty minutes after its administration iodotyrosine (50 mg/kg) caused a highly significant (P less than 0.0005) rise in serum prolactin and a highly significant (P less than 0.0025) fall in the concentration of dopamine in the hypothalamus and median eminence where the levels reached 50% of control levels. Less marked but significant falls were also observed in the hypothalamic (P less than 0.05) and median eminence (P less than 0.0025) concentrations of noradrenaline after iodotyrosine administration. Serotonin concentration was significantly reduced (P less than 0.025) in the median eminence but not in the hypothalamus after iodotyrosine administration. These findings suggest that iodotyrosine exerts its prolactin stimulating effect by blockage of dopamine synthesis rather than by receptor blockade.

Animals↗
PubMed1979

Acromegaly.

Explore the source record for details and available documents.

Acromegaly↗
PubMed1979

Immune complexes in diabetes mellitus.

Sera from 86 well controlled diabetics were examined for the presence of immune complexes. Thirty-six patients were receiving standard insulins, 19 monocomponent preparations, 24 oral hypoglycaemic agents and seven dietary restriction alone. Three methods were used to detect complexes: measurement of complement components, a Clq binding assay (BA) and the Raji cell radioimmunoassay (RIA). Complement components were normal in all patients. Eleven (31%) of the group on standard insulins had a positive Raji cell RIA; none had an abnormal Clq-BA. One patient on monocomponent therapy had a mildly positive Raji cell RIA; Clq-BA was negative in each patient of this group. Thirteen (54%) of the patients on oral hypoglycaemic agents were positive on one or both assays while one patient on diet alone was abnormal on both assays. These data show that immune complex production is common in both insulin-requiring and non-insulin-requiring diabetics and that this phenomenon is strikingly less frequent in patients on monocomponent insulins. Such observations could bear relevance to the pathogenesis of microvascular complications in diabetes.

Adolescent↗
PubMed1979

Release of secretin--plasma levels reproduced by exogenous infusion.

Infusion of 0.1 M HCl (0.5 mmol/kg/hr over 20 minutes) into the duodenum of each of seven normal subjects led to a significant rise (P less than 0.05) in mean plasma secretion levels from 3.0 +/- 2.2 (SE) to 15 +/- 4.0 pmol/l. Intravenous infusion of secretin at a rate of 6.6 pmol/kg/hr (0.08 clinical units/kg/hr) reproduced the peak plasma levels of secretin observed during duodenal acidification. However, there was no detectable (2.5 pmol/l) change in plasma secretin after oral protein or glucose.

Duodenum↗