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Biomedical subjects

J Wortsman

Publications and source records attributed to J Wortsman.

At least 19 recordsLinked to original sources
PubMed1992

T-lymphocyte activation in adult-onset idiopathic hypoparathyroidism.

PURPOSE: Patients with adult-onset idiopathic hypoparathyroidism (AOIH) often have antibodies against the parathyroid glands and other tissues, suggestive of immune activation. The purpose of this study was to determine whether T-cell activation is also a component of the endocrine disease. PATIENTS AND METHODS: We identified eight patients with idiopathic hypoparathyroidism diagnosed after the age of 30 years at two tertiary care centers and evaluated peripheral blood lymphocyte subset phenotype frequencies using monoclonal antibodies and flow cytometry. Control subjects were 13 patients with Graves' disease (five thyrotoxic and eight euthyroid) and 110 healthy volunteers. In two of the patients with AOIH, we also determined the mitogenic response to parathyroid cell membranes in peripheral lymphocytes. RESULTS: Patients with AOIH had higher than normal frequencies of the following phenotypes (p less than 0.05 versus controls, one-way analysis of variance): CD4, helper T cells; CD29/CD4, inducer of helper T cells; CD16 and CD56, natural killer cells; and CD3/DR, activated T cells coexpressing DR. Patients with Graves' disease had significantly higher than control frequencies of CD25 (T cells bearing the interleukin-2 receptor), CD3/DR, and CD26 (also a marker of T-cell activation); whereas the frequency of CD29/CD4 was significantly less than the control frequency. Neither of the two AOIH patients tested showed lymphocyte proliferation in response to parathyroid or thyroid cell membrane fractions. CONCLUSIONS: Generalized T-cell activation represents a novel feature associated with AOIH. Although we could not demonstrate parathyroid-specific lymphocyte clonal expansion, these data are suggestive of a generalized immune disturbance possibly related to autoimmunity, in which one of the manifestations is hypoparathyroidism.

Adult↗
PubMed1992

Melanotropic activity of gamma MSH peptides in melanoma cells.

We studied the pigmentary activity of the peptides gamma 1, gamma 2 and gamma 3 melanocyte stimulating hormone (MSH), which differ in the structure of their C-termini, using hamster and mouse melanoma cell lines responsive to beta-MSH by increasing tyrosinase activity. Gamma 1-MSH alone or in combination with beta-MSH had no effect on either cell line. Gamma 2-MSH alone was biologically inactive but potentiated beta-MSH stimulation of tyrosinase activity. Gamma 3-MSH at high concentration (10 microM) induced tyrosinase activity and dendrite formation in the hamster melanoma line. When added together with beta-MSH, gamma 3-MSH partially inhibited the tyrosinase activity response to beta-MSH. Thus, gamma-MSH peptides have low intrinsic melanotropic activity in mammalian melanoma cells; the specific pigmentary responses appear to be affected by the structure of the C-terminal portion.

Amino Acid Sequence↗
PubMed1992

Elevation of blood vitamin D2 levels does not impede the release of vitamin D3 from the skin.

The mechanism for the transfer of fat-soluble vitamin D3 from the avascular basal cellular layers of the epidermis to dermal capillaries and peripheral circulation is unknown, although vitamin D-binding protein (DBP) is thought to mediate this process. To evaluate the effect of increased occupancy of vitamin D carrier(s) on vitamin D3 removal from the skin, serial serum vitamin D2 and D3 concentrations were determined in three groups of six healthy volunteers given combinations of an oral dose of vitamin D2 (50,000 IU) and a fixed dose of UVB radiation (27 mJ/cm2). Serum vitamin D3 levels increased significantly following UVB (time effect, P < .01 by ANOVA), but the response remained unchanged after pretreatment with vitamin D2, increasing from 3 +/- 1 to 14 +/- 5 ng/mL (mean +/- SEM), versus UVB alone, 5 +/- 1 to 16 +/- 5 ng/mL. Elevation of serum vitamin D2 levels was also similar in the groups given vitamin D2 alone (< 1 to 64 +/- 8 ng/mL) and vitamin D2 + UVB (< 1 to 45 +/- 8 ng/mL). There was no time or treatment effect for changes in serum levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or (DBP) levels (P > .1). We conclude that vitamin D3 egress from the skin is not affected by elevated circulating vitamin D concentrations; thus, the cutaneous release of vitamin D is probably mediated by a protein such as DBP with a high carrying capacity for the vitamin.

Administration, Oral↗
PubMed1992

Clothing prevents ultraviolet-B radiation-dependent photosynthesis of vitamin D3.

Photoprotection of the skin is mainly a function of clothing, although the effectiveness of the latter against UV-B solar radiation (wavelengths 290-320 nm) has not been measured in vivo. Since UV-B mediates the cutaneous formation of vitamin D3, we examined the attenuation of that photosynthetic reaction by the commonly used fabrics cotton, wool, and polyester in black and white colors. Direct transmission of UV-B was attenuated the most by black wool (98.6% of incident irradiance) and the least by white cotton (47.7%). None of the fabrics allowed the photoproduction of previtamin D3 from 7-dehydrocholesterol irradiated in vitro with up to 40 min of simulated sunlight or the elevation of serum vitamin D3 after irradiation with approximately one minimal erythema dose (MED) of UV-B in volunteers wearing jogging garments made of these fabrics. Increasing the whole body irradiation dose to six MEDs still failed to produce a serum vitamin D3 response in garment-clad subjects. Regular (seasonal) street clothing also prevented an elevation of the vitamin D3 in response to UV-B radiation. We conclude that clothing prevents or significantly impairs the formation of vitamin D3 after photostimulation with up to six MEDs of UV-B.

Adult↗
PubMed1991

The effect of standard- and high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation.

We studied the effect of standard and high doses of epinephrine on coronary perfusion pressure during cardiopulmonary resuscitation in 32 patients whose cardiac arrest was refractory to advanced cardiac life support. Simultaneous aortic and right atrial pressures were measured and plasma epinephrine levels were sampled. Patients remaining in cardiac arrest after multiple 1-mg doses of epinephrine received a high dose of 0.2 mg/kg. The increase in the coronary perfusion pressures was 3.7 +/- 5.0 mm Hg following a standard dose, not a statistically significant change. The increase after a high dose was 11.3 +/- 10.0 mm Hg; this was both statistically different than before administration and larger than after a standard dose. High-dose epinephrine was more likely to raise the coronary perfusion pressure above the previously demonstrated critical value of 15 mm Hg. The highest arterial plasma epinephrine level after a standard dose was 152 +/- 162 ng/mL, and after a high dose, 393 +/- 289 ng/mL. Because coronary perfusion pressure is a good predictor of outcome in cardiac arrest, the increase after high-dose epinephrine may improve rates of return of spontaneous circulation.

Aorta↗
PubMed1991

Plasma chromogranin A as a marker of sympathochromaffin activity in humans.

The extent to which the sympathochromaffin system compared with other endocrine/neuroendocrine tissues contributes to the plasma chromogranin A pool has not been defined. To test the hypothesis that the sympathochromaffin system is the major source of circulating chromogranin A only when that system is activated markedly, we measured chromogranin A concentrations in 200 human plasma samples known to have a broad range of norepinephrine and epinephrine concentrations, reflecting therefore a broad range of sympathochromaffin activity at the time of sampling. Plasma chromogranin A and norepinephrine concentrations were highly correlated when the sympathochromaffin system was activated markedly (cardiac arrest samples, n = 13, r = 0.8392, P less than 0.0005) and when there was release of large amounts of norepinephrine from tumors (pheochromocytoma samples, n = 17, r = 0.8132, P less than 0.001). However, when the sympathochromaffin system was activated less markedly, resulting in plasma catecholamine concentrations that spanned the physiological and lower pathophysiological range (nonpheochromocytoma noncardiac arrest samples, n = 170), correlations between plasma chromogranin A and norepinephrine (r = 0.2877, P less than 0.0001) and epinephrine (r = 0.3814, P less than 0.0001) levels were relatively weak, although still statistically significant. Thus, at basal through moderate stress levels, norepinephrine and epinephrine concentrations accounted for only approximately 10-15% of the variance in plasma chromogranin A levels. We conclude that, although plasma chromogranin A concentrations are a valid marker of sympathochromaffin activity in humans, they are not a sensitive marker under physiological conditions.

Adrenal Gland Neoplasms↗
PubMed1991

Cutaneous vitamin D3 formation in progressive systemic sclerosis.

Progressive systemic sclerosis (PSS) is a predominantly dermal disorder which may be associated with epidermal atrophy. We investigated epidermal function in 8 patients with PSS and their healthy controls matched for age, sex and racial group. We measured the vitamin D3 photosynthetic response to whole body irradiation with ultraviolet light B (UVB). There were no significant differences in basal serum vitamin D3 levels (mean +/- SEM: PSS 1.2 +/- 0.2 ng/ml; controls 0.8 +/- 0.1 ng/ml; p greater than 0.1) or post UVB blood values (PSS 5.2 +/- 1.4 ng/ml; controls 6.9 +/- 1.1 ng/ml; p greater than 0.1); although the increases post-UVB were significant in both groups (p less than 0.01). In an additional group of 19 patients with PSS and their corresponding matched healthy controls, we performed determination of random levels of the active vitamin D metabolites, 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D [1,25-(OH)2-D]. Similar levels were observed in both groups: 25-OH-D PSS 28 +/- 3 ng/ml, controls 29 +/- 3 ng/ml; 1,25-(OH)2-D PSS 27 +/- 2 pg/ml, controls 31 +/- 2 pg/ml (p greater than 0.1). None of the correlations between skin area involved and vitamin D3 formation or active circulating metabolites reached statistical significance (p greater than 0.1). We conclude that global epidermal synthesis of vitamin D is retained in PSS and, that the hepatic and renal vitamin D hydroxylating mechanisms function normally in that condition.

Adult↗
PubMed1991

Gestational diabetes and neonatal macrosomia in the polycystic ovary syndrome.

Since patients with polycystic ovary syndrome (PCOS) commonly have insulin resistance, albeit with normal glucose tolerance, we evaluated glucose tolerance in PCOS patients exposed to the diabetogenic effect of pregnancy. The clinical material was obtained from two centers, in Springfield, Illinois (22 patients), and New York, New York (31 patients), and the results were compared with a control population with 2,306 consecutive general pregnancies. There were no differences between PCOS patients from the two centers in regard to age or ponderal index (P greater than .1). A review of the medical records showed that the incidence of gestational diabetes in the PCOS patients was 7.5%, similar (P greater than .1) to the 6.6% frequency of gestational diabetes in the controls. The overall incidence of neonatal macrosomia (birth weight greater than 4,000 g) was 7% (4 of 57) among infants born to PCOS women. That was similar to the 12.4% incidence of neonatal macrosomia among infants born to women with normal glucose tolerance and to the 14.5% incidence among infants born to women with gestational diabetes. Preexisting PCOS does not appear to increase the risk of developing gestational diabetes or neonatal macrosomia.

Adult↗
PubMed1991

Racial pigmentation and the cutaneous synthesis of vitamin D.

The varying epidermal melanin content that produces racial pigmentation determines the number of photons that reach the lower (malpighian) cellular layers, where vitamin D3 synthesis takes place. We investigated the effect of racial pigmentation on vitamin D3 formation, stimulating the process with a fixed dose of UVB radiation (wavelengths, 290 to 320 nm). Vitamin D nutritional status was further assessed measuring serum 25-hydroxyvitamin D and the most active serum metabolite, 1,25-dihydroxyvitamin D. Experimental subjects were young (third decade of life) and healthy, representing the white, Oriental (East Asian), Indian (South Asian), and black races. Basal serum vitamin D3 levels were similar among groups, ranging from 2.3 +/- 0.6 nmol/L (mean +/- SEM) for blacks to 3.4 +/- 1.0 nmol/L for Indians. Following whole-body exposure to 27 mJ/cm2 of UVB, there was a significant racial group effect on serum vitamin D3 levels. Post-UVB levels were significantly higher in whites (31.4 +/- 4.4 nmol/L) than in Indians or blacks (12.8 +/- 2.9 and 9.1 +/- 2.1 nmol/L, respectively), while the levels in Orientals (27.8 +/- 4.4 nmol/L) differed significantly from those in blacks and Indians but not in whites. Race had only a marginal effect on serum 25-hydroxyvitamin D, with higher levels in whites than in blacks (69.9 +/- 12.7 vs 29.7 +/- 6.2 nmol/L). Serum 1,25-dihydroxyvitamin D and vitamin D binding protein levels were similar in all groups. We conclude that while racial pigmentation has a photoprotective effect, it does not prevent the generation of normal levels of active vitamin D metabolites.

Adult↗
PubMed1991

Elastase inhibitory activity in serum of patients with thyroid dysfunction.

Dermal elastic fiber fragmentation and decreased fiber density are characteristic cutaneous abnormalities in myxedema. We therefore evaluated elastase inhibitory activity in serum in thyroid dysfunctional states by measuring the protease inhibitor alpha 1-antitrypsin (A-1-AT), as well as by directly determining the inhibition of porcine pancreatic elastase activity. Overall there was a strong correlation between A-1-AT concentration and elastase inhibitory activity in serum (r = 0.95, P less than 0.001). Mean (+/- SE) A-1-AT concentrations were greatest in hyperthyroidism (39 +/- 3 mumol/L, n = 13), followed by normal controls (29 +/- 1, n = 11), subclinical hypothyroidism (27 +/- 2, n = 7), and hypothyroidism (25 +/- 1, n = 12). Concentrations of both A-1-AT and porcine pancreatic elastase inhibitory activity were significantly greater in subjects with hyperthyroidism than in the other groups (P less than 0.01). The correlations (r) between the overall free thyroxin (T4) index and A-1-AT and elastase inhibitory activity were 0.68 and 0.61, respectively (P less than 0.01), implying that free T4 variations account for 46% of the variance in A-1-AT concentrations and 37% of the variance in elastase inhibitory activity. We conclude that serum elastase inhibitory activity is increased in hyperthyroid patients.

Adult↗
PubMed1991

Clinical significance of the solitary functioning adrenal gland.

To assess the compensatory functional and anatomic changes in the remaining adrenal cortex after unilateral adrenalectomy or in the unaffected adrenal in patients with unilateral adrenal destruction by neoplasm, 17 patients with a single, functioning adrenal gland and normal indices of adrenocortical function, nine after adrenalectomy and eight with a unilateral, destructive adrenal lesion were studied with 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy and computed tomography. Adrenal masses with a mean (+/- s.d.) diameter of 2.8 +/- 1.0 cm; (range 1-4 cm; 95% confidence interval (Cl), 2.5-3.1 cm) were identified by computed tomography in seven of nine patients in the remaining adrenal cortex at variable times (6.1 +/- 5.9 y; range 0.5-19 y) after unilateral adrenalectomy. Mean (+/- s.e.m.) NP-59 uptake was elevated (p less than 0.01) in both adrenalectomy and adrenal destruction groups, mean uptake (+/- s.e.m.) was 0.32% +/- 0.04% administered dose (95% Cl, 0.24%-0.4% administered dose) as compared to normal (0.16% +/- 0.05% administered dose, 95% Cl, 0.06%-0.26% administered dose). The remaining adrenal cortex may be anatomically abnormal after unilateral adrenalectomy and demonstrate compensatory, increased NP-59 uptake in the presence of overall, normal adrenocortical function.

Adosterol↗
PubMed1979

Cyproheptadine in the management of the galactorrhea-amenorrhea syndrome.

We evaluated long-term treatment with the antiserotonergic agent cyproheptadine in the management of the galactorrhea-amenorrhea syndrome. Fifteen women with a mean initial serum prolactin of 37 +/- 7 ng/mL received 16 to 24 mg of cyproheptadine daily; they had a significant decrease in prolactin concentration at 8 and at 16 weeks (P less than 0.01). Gonadotropin responses were variable, but no significant changes were recorded during treatment. Ten of the 15 women had menstrual bleeding while receiving cyproheptadine, seven had decreased galactorrhea, and two had cessation of galactorrhea. The side effects of treatment were transient drowsiness and weight gain. We conclude that long-term treatment of the galactorrhea-amenorrhea syndrome with cyproheptadine is effective in lowering serum prolactin in patients with mildly elevated or normal levels. Its effect on fertility remains to be ascertained.

Adult↗
PubMed1979

Clinical resistance to vasopressin. Detection of antibody by hemagglutination.

We describe a patient with hypothalamic diabetes insipidus who after 20 years became refractory to the effect of commercial vasopressin injection. Vasopressin antibodies were measured using a sensitive hemagglutination technique. Resistance was associated with a high titer of antibodies that disappeared once vasopressin therapy was withdrawn and the diabetes insipidus was controlled with chlorpropamide. Antibodies were also measured in four additional patients with diabetes insipidus while they were or were not receiving vasopressin. A patient who had received the drug for only two years already had a substantial titer of antibodies to vasopressin, but in this case the response to the hormone was not impaired.

Adolescent↗