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Biomedical subjects

V Pezzino

Publications and source records attributed to V Pezzino.

14 recordsLinked to original sources

Identification and initial characterization of insulin receptor-like immunoreactivity in human plasma.

With a two-step purification procedure employing sequential affinity chromatography with insulin receptor monoclonal antibody followed by wheat germ agglutinin, we isolated from the plasma of two healthy individuals a material that reacted in a specific RIA for insulin receptors. This material produced dilution curves that were parallel to a human placental insulin receptor standard. This material also bound [125I]insulin; competition-inhibition curves revealed an ED50 of 0.3 nM, a value similar to that obtained with placental insulin receptors. The material purified from plasma was then labeled with [125I] Bolton-Hunter reagent, followed by polyacrylamide gel electrophoresis under reducing conditions and autoradiography. A band at 135 kilodaltons (kDa) was observed, corresponding to the alpha-subunit of the insulin receptor. Several bands ranging from 82-46 kDa were also detected. One or more of these fragments had intrinsic autophosphorylation activity, but only the 82-kDa band activity was responsive to insulin. In addition, employing the synthetic substrate poly(Glu4:Tyr1), no insulin-sensitive tyrosine kinase activity was present. These studies demonstrate, therefore, that insulin receptor-derived material is present in human plasma. This material retains high affinity insulin binding, but has an altered beta-subunit that is devoid of insulin-responsive tyrosine kinase activity.

Humans

Insulin and glucagon receptors in Morris hepatomas of varying growth rates.

The binding of both insulin and glucagon to receptors in plasma membranes from five hepatomas of varying growth rates was diminished when compared to plasma membranes from normal liver. Scatchard analyses of the binding data suggested that the decrease in glucagon binding was due to a decrease in binding capacity, whereas the decrease in insulin binding was due either to a decrease in binding affinity or to site-site interactions. The decreased binding of insulin, but not of glucagon, showed a significant correlation with increasing growth rate of the tumors. These data suggest, therefore, that decreased binding of insulin to receptors could be a feature of increasing growth rate in hepatomas.

Adenosine Triphosphatases

Increased serum thyroglobulin levels in patients with nontoxic goiter.

Thyroglobulin (Tg) levels were found to be elevated in 30 to 35 patients with euthyroid sporadic goiter and in 15 of 37 patients with euthyroid endemic goiter. The elevated Tg levels in the goitrous patients did not correlate with either goiter size, TSH levels, or urinary iodine excretion, but did correlate with the triiodothyronine to thyroxine ratio. It was concluded, therefore, that in both sporadic and endemic euthyroid goiters, factors other than goiter size and TSH, such as hypoiodination of Tg may be responsible for the elevated Tg secretion.

Adult

A radioimmunoassay for human thyroglobulin: methodology and clinical applications.

A specific double-antibody radioimmunoassay with a sensitivity of 2.5 ng/ml has been developed for measuring thyroglobulin (Tg) in human serum. As endogenous anti-Tg antibodies in serum interfere in the assay, only sera with a negative tanned red cell (TRC) test are suitable for analysis. Tg was detectable in 84.7% of the euthyroid subjects, with a mean value of 6.1 (values ranging from nondetectable to 43.0 ng/ml). Values were significantly higher in women than in men. Tg release by the thyroid appears to be under pituitary control, as suggested by TSH stimulation and T3 suppression tests. Elevated Tg levels were found in hyperthyroidism, simple goitre, and differentiated thyroid carcinoma. The significance of circulating Tg and the possible application of the Tg RIA are discussed.

Adolescent

Thyrotropin and prolactin response to intraspinal TRH administration in man.

The effect of intraspinal (i.s.) TRH administration of Prolactin (Prl) and thyrotropin stimulating hormone (TSH) serum levels was studied in order to verify the existence of a ventricular route in man for releasing factor delivery to the anterior pituitary, which has been previously reported in rats. Ten young male subjects were given 200 microgram thyrotropin releasing hormone (TRH) i.s. injections and Prl and TSH were measured by radioimmunoassay (RIA) before and at various times after TRH administration. In the same subjects, an i.v. TRH test was also performed. After i.s. TRH, a prompt Prl increase (peak values at 10-30 min and return to baseline within 150 min) and a delayed increase (3-5 h following TRH injection) were observed in 7 and 5 subjects respectively, while an early elevation in serum TSH occurred in 6 subjects and a late one in other 6. In two subjects, a biphasic response of both tropins was present. Prl and TSH response to i.v. TRH was within the normal range in all cases; no late rise of the 2 hormones was observed. A kinetic experiment with 125I-TRH was also carried out to elucidate the mode of i.s. vs i.v. TRH action. These results confirm in man data reported in animals which suggest that TRH can be transported from the cerebrospinal fluid (CSF) to the portal system and the hypophysis.

Humans

Decrease of prolactin by methysergide in amenorrheic hyperprolactinemic women.

The effect of methysergide (MES), a serotoninergic antagonist on prolactin (PRL) blood levels was studied in five hyperprolactinemic amenorrheic women. The drug was administered for five days at a daily dosage of 11.2 mg. MES decreased significantly the PRL blood levels in all subjects (p less than 0.01). Since the MES has been shown to have antiserotoninergic effects and since serotonin has been thought to be involved in the control of PRL release, the effects of MES in lowering PRL might be due to a decrease of serotonin tone.

Adolescent

Growth hormone levels in diabetes. Correlation with the clinical control of the disease.

We carried out contemporaneous daytime blood sugar and growth hormone (HGH) determinations in eight juvenile and six middle-aged diabetics under both poor and good metabolic control. A continuous blood sampling technic was used. The following results were obtained: 1. HGH values in poorly controlled diabetics were higher and more fluctuating than in normals of a corresponding age. 2. After good control was reached, a significant HGH decrease was observed in all patients but one. In this condition HGH levels were normalized in middle-aged diabetics but not in juvenile ones. In the latter group HGH values, even if decreased, were persistently higher than in controls of the same age. 3. No difference was observed between newly diagnosed diabetics and patients known to have had diabetes for some years. Our data support the suggestion that HGH abnormalities in diabetes are a consequence of the metabolic disturbance.

Adolescent

Effect of dexamethasone on thyroid hormone response to TSH.

The effect of short-term dexamethasone administration (8 mg daily for 3 days) on thyroid hormone response to exogenous TSH (bovine TSH, 5 IU i.m.) was studied in 16 euthyroid volunteers. Serum T3 and T4 concentrations were measured by radio-immunoassay prior to and 2, 6, 12, 24, and 49 hr after bTSH injection, both under basal conditions and during dexamethasone treatment. In all subjects bTSH administration raised both T3 and T4 concentrations significantly. Dexamethasone treatment induced a slight depression of endogenous TSH (m +/- SEM = 2.0 +/- 0.4 versus 1.6 +/- 0.3 muU/ml) and T4 (6.8 +/- 0.4 versus 6.1 +/- 0.2 mug/100 ml) basal values and a significant decrease in T3 value (1.16 +/- 0.09 versus 0.64 +/- 0.06 ng/ml, p = 0.005). The mean increment of both T3 and T4 after bTSH injection was percentually unchanged during dexamethasone treatment but, due to lowered basal value, T3 levels at each time interval after TSH + dexamethasone were significantly lower than the corresponding values observed after TSH alone. The present data show that high dexamethasone doses decrease T3 serum levels significantly without inhibiting T3 response to TSH stimulation. Only a slight lowering was observed in T4 levels.

Adolescent

Spontaneous fluctuations of human placental lactogen during normal pregnancy.

Six women in the 3rd trimester of normal pregnancy had measurements of circulating placental lactogen (hPL) levels using a continuous blood sampling technique for 10-15 h. In addition, in 3 pregnant women hPL was assayed at 10-min intervals for 60-90 min. Both these procedures showed that hPL serum levels fluctuate irregularly during normal pregnancy. The magnitude and frequency of these fluctuations make the significance of a single hPL determination less reliable as a test of placental function.

Adult

The effect of short-term triiodothyronine administration on thyroxine response to exogenous TSH in man.

In order to examine whether thyroid hormone concentration interfere with the thyroid gland responsivity to TSH, paired studies on the effect of short-term T3 treatment on T4 response to exogenous TSH ( 5 I.U. i.m.) were carried out in 10 euthyroid volunteers. During T3 administration ( 120 mcg/day for 4 days starting 48 hr before TSH injection) a significant decrease in T4 concentrations was observed both prior to and after TSH, with an inhibition of the T4 response ranging from 36-77% as calculated from the area under the response curve. The present data are in agreement with the existence of a "short-loop" thyroid-thyroid regulatory mechanism in man. In fact, the decreased percent rise of T4 after TSH suggests an inhibitory effect of T4 release following TSH, even though a modification of T4 kinetic parameters during T3 administration may account for a portion of the lowering of T4 blood concentrations.

Adult