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Biomedical subjects

J Wortsman

Publications and source records attributed to J Wortsman.

At least 55 records · Page 3Linked to original sources
PubMed1996

Celiac disease and hypoparathyroidism: cross-reaction of endomysial antibodies with parathyroid tissue.

Celiac disease (CD) is a gluten-sensitive enteropathy characterized by the presence of serum antibodies to endomysial reticulin and gliadin antigens. CD has been associated with various autoimmune endocrine disorders, such as diabetes. We report a rare case of idiopathic hypoparathyroidism with coexistent CD characterized by the presence of serum autoantibodies. Studies were conducted to determine the specificities of these autoantibodies and to localize the antibody binding sites by indirect immunofluorescence and immunoelectron microscopy. Sera from a patient with idiopathic hypoparathyroidism and CD and from two patients with CD alone were tested by indirect immunofluorescence for autoantibodies to parathyroid and endomysial antigens. The specificities of the antibody reactions were determined by testing the sera before and after absorption with monkey stomach tissue. In addition, immunoelectron microscopic studies were performed to determine the localization of the endomysial antigen. Indirect-immunofluorescence studies on the patient's serum were positive with the parathyroid as well as the endomysial substrate. Similar reactions were also observed with the sera of endomysial antibody-positive patients with CD. Absorption of the sera with monkey stomach powder, which is known to have the endomysial antigen, abolished the antibody activities on both the endomysial substrate and the parathyroid tissue. Immunoelectron microscopic studies showed that endomysial antibody activity was associated with antigens localized on the myocyte plasma membrane and in the intercellular spaces. Thus, reactions of the patient's serum with the parathyroid tissue were due to endomysial antibodies and were not parathyroid specific as in patients with idiopathic hypoparathyroidism who did not have coexistent CD. In conclusion, indirect-immunofluorescence tests on parathyroid tissue detect not only tissue-specific antibodies but also cross-reactive antibodies, and this should be taken into consideration when these tests are performed.

Autoantibodies↗
PubMed1995

Inhibin in normal and abnormal pregnancy: maternal serum concentration and partial characterization.

OBJECTIVE: This study evaluated maternal serum inhibin concentration and molecular distribution in normal and abnormal pregnancies. STUDY DESIGN: Serum inhibin levels were measured by radioimmunoassay in 33 abnormal pregnancies (23 singleton and 10 multiple gestations) and 33 matched controls and were compared with pregnancy variables. RESULTS: In the controls serum inhibin concentrations rose with gestational age (correlation coefficient 0.358, p < 0.01) and were higher in mothers with female fetuses (p < 0.05). Inhibin levels were higher in the abnormal singleton pregnancies (2.69 +/- 1.41 ng/ml) than in controls (1.26 +/- 0.32 ng/ml, p < 0.0001) and increased more rapidly with gestational age in multiple pregnancies (p < 0.05). Gel filtration chromatographic analysis of immunoreactive inhibin revealed three peaks with the major form having an apparent molecular weight of 55 to 60 kd. CONCLUSION: Maternal serum inhibin concentrations are affected by gestational age, fetal gender, and complications of pregnancy. Most of the immunoreactive inhibin in maternal circulation is a large-molecular-weight form.

Case-Control Studies↗
PubMed1995

Thyroids from siblings with Pendred's syndrome contain thyroglobulin messenger ribonucleic acid variants.

We studied thyroid tissue from two siblings with Pendred's syndrome (familial goiter and congenital deafness), both with the Mondini-type inner ear malformation, goiter, and hypothyroidism. Iodine trapping and peroxidase levels were grossly normal. Thyroglobulin (Tg), the only iodoprotein found, had a normal monomer size (330 kilodaltons), but low content of hormone and iodine. Tg's expected N-terminal peptides of 26 and 18 kilodaltons, usually formed in association with iodination and thyroid hormone synthesis, were absent, but appeared after iodination in vitro. Reverse transcription of ribonucleic acid from Pendred thyroid tissue and amplification by polymerase chain reaction of specific regions encoding the most important hormonogenic sites of Tg revealed a normal complementary DNA sequence corresponding to the first 100 amino acid residues in Tg's N-terminus. However, 3 of 35 clones of the 3'-region corresponding to the Tg C-terminus exhibited a deletion of nucleotides 7860-7994; this deletion was not present in any of the 150 clones from 7 other thyroids we examined. Four Pendred clones had a 2-nucleotide deletion at positions 7870-7871, a change that would result in a premature stop codon and was found in thyroids from several other subjects as well. We conclude that the messenger ribonucleic acid encoding the 3'-region of Tg can be abnormal in Pendred's syndrome. Some, but not all, of these changes also occur in other human thyroids. Further work is necessary to show if and how these alterations relate to defective hormone synthesis and goiter.

Adult↗
PubMed1995

Compensation for the interracial variance in the cutaneous synthesis of vitamin D.

We investigated the homeostatic compensation for the lower cutaneous synthesis of vitamin D in heavily melanized persons. Vitamin D2 (50,000 IU) was administered in a single oral dose to 24 young adults, 12 blacks and 12 whites, matched for age, gender, and socioeconomic status. We also included a group of eight healthy elderly white adults as representatives of a population with a nonracial mechanism for decreased cutaneous vitamin D synthesis. Plasma determinants were performed under basal conditions and at 6, 10, and 24 hours after vitamin D intake. Basal 25-hydroxyvitamin D (25-OH-D) levels were significantly lower in blacks (12.5 +/- 2.2 ng/ml (mean +/- SEM)) and in elderly whites (19.2 +/- 1.9 ng/ml), compared with young whites (30.2 +/- 3.0 ng/ml (p < 0.0001)); levels of basal 1,25-dihydroxyvitamin D (1,25(OH)2 -D) did not differ between groups. The vitamin D blood curve was similar between groups after the oral vitamin D2 load. Increases in 25-OH-D were 91.7 +/- 15.9% in blacks, 18.8 +/- 5.2% in young whites, and 28.6 +/- 6.9 in elderly whites; 1,25(OH)2-D levels increased slightly and did not differ between groups, although in blacks the change over time was significant (p < 0.05). As a whole, the study populations exhibited a strong relation between basal and peak 25-OH-D (r = -0.80; p < 0.001). Levels of intact parathyroid hormone and serum calcium of blacks and young whites did not differ within or between groups throughout the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Case report: idiopathic hypoparathyroidism co-existing with celiac disease: immunologic studies.

Idiopathic hypoparathyroidism (IH) is often an isolated disorder in adults, but in children it is usually a component of the autoimmune polyendocrinopathy syndrome. The authors describe a patient diagnosed with isolated IH at age 57 and celiac disease at age 64. Testing of patients' serum show antibodies of the immunoglobulin A isotype against endomysium, reticulin, and gliadin antigens, as well as immunoglobulin G against gliadin. The circulating immunoglobulins reacted with bovine parathyroid tissue, specifically smooth muscle of the blood vessels and glandular cells, as detected by indirect immunofluorescence. Testing of celiac disease positive sera showed similar parathyroid reactivity. When the patient was placed on a gluten-free diet, endomysial, reticulin, and gliadin antibodies decreased to undetectable levels, which was parallel with disappearance of the parathyroid immunoreactivity. The gluten-free diet also produced severe hypercalcemia that responded to calcitriol withdrawal, and ultimately required a reduction by half of the original calcitriol dose. It is possible that in this case the same antibody or antibodies may have caused both hypoparathyroidism and celiac disease. We conclude that, as in the case of childhood-onset IH variants, patients with late-onset isolated IH should be monitored for additional endocrine and extra-endocrine autoimmune disorders.

Celiac Disease↗
PubMed1994

High atrial natriuretic peptide concentrations blunt the pressor response during cardiopulmonary resuscitation in humans.

OBJECTIVE: To determine the relationship of circulating atrial natriuretic peptide concentrations to the pressor response to high-dose epinephrine in patients undergoing cardiopulmonary resuscitation (CPR) for cardiac arrest. DESIGN: Prospective study. PATIENTS: Fourteen normothermic, adult, prehospital and emergency department patients suffering unexpected cardiac arrest. INTERVENTION: Patients received high-dose epinephrine (0.2 mg/kg) i.v. when standard advanced cardiac life support (including multiple 1-mg dosages of epinephrine) failed to result in return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: Cardiac arrest patients were separated into those patients with and without detectable serum atrial natriuretic peptide concentrations, and were termed the "low atrial natriuretic peptide" and "high atrial natriuretic peptide" groups, respectively. Their aortic pressure response to high-dose (0.02 mg/kg) epinephrine was compared. The proportion with positive assays was compared with a group of healthy control subjects. Fourteen patients were studied. Eight patients had low serum atrial natriuretic peptide concentrations and six patients had high circulating atrial natriuretic peptide concentrations. The mean concentration in the high atrial natriuretic peptide group was 151 +/- 82 pg/mL. The proportion with positive assays (six of 14 patients) was greater than in the group in spontaneous circulation (three of 29 patients) (p = .002). The maximal increase in the aortic relaxation-phase pressures after high-dose epinephrine was 9 +/- 7 torr (1.2 +/- 0.9 kPa) in the low atrial natriuretic peptide group and 0 +/- 5 torr (0 +/- 0.7 kPa) in the high atrial natriuretic peptide group (p = .03). The maximal increase in the aortic compression pressures after high-dose epinephrine was 17 +/- 13 torr (2.3 +/- 1.7 kPa) in the low atrial natriuretic peptide group and 2 +/- 10 torr (0.3 +/- 1.3 kPa) in the high atrial natriuretic peptide group (p = .03). Thus, pressor responses after high-dose epinephrine administration were observed in patients in the low atrial natriuretic peptide group, but this response was absent in patients in the high atrial natriuretic peptide group. CONCLUSIONS: Cardiac arrest patients receiving CPR have higher circulating atrial natriuretic peptide concentrations than healthy subjects. High serum atrial natriuretic peptide concentrations may antagonize the vasopressor response to epinephrine. Blocking this effect of atrial natriuretic peptide may improve outcomes in patients suffering cardiac arrest.

Adult↗
PubMed1994

The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period.

BACKGROUND: Studies evaluating the dose of epinephrine required to optimize return of spontaneous circulation and survival after CPR have shown that doses greater than recommended by advanced cardiac life support (ACLS) improve coronary perfusion pressure and short-term resuscitation rates. Since survival has not improved, it is possible that higher doses of epinephrine may be physiologically detrimental in the postresuscitation period. OBJECTIVE: The object of this study is to measure the effect of the total cumulative dose of epinephrine given during ACLS on the hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. DESIGN: A prospective nonrandomized control trial of inception cohorts. SETTING: A large urban emergency department and intensive care unit. PATIENTS: Forty-nine successfully resuscitated witnessed, normothermic, nontraumatic, out-of-hospital patients, who had suffered cardiac arrests. INTERVENTIONS: All patients were treated according to ACLS guidelines; however, the epinephrine dose (0.01 to 0.2 mg/kg or 1 to 14 mg) was selected at the clinician's discretion and given through central venous access every 3 to 5 min. Hemodynamic, oxygen transport, and utilization variables were measured on a return of spontaneous circulation, and at least every 30 min thereafter under a standardized postresuscitation protocol. MAIN OUTCOME MEASURES: Hemodynamic, oxygen transport/utilization variables, and mortality in patients resuscitated from cardiac arrest. The total cumulative dose of epinephrine given during ACLS until a return of spontaneous circulation was recorded. RESULTS: A total cumulative epinephrine dose of 15 mg was found to best predict 24-h mortality. Of the 49 patients, 20 received less than 15 mg (group 1) and 29 received greater than 15 mg (group 2). Age, premorbid health status, sex, presenting rhythm, and duration of cardiac arrest were similar in both groups. The 24-h survival was 17 of 20 (85%) and 12 of 29 (41%) in group 1 and 2, respectively (p < 0.002). Over the first 6 h of the postresuscitation period, both groups had similar mean arterial pressure (MAP), mixed venous oxygen saturation, and systemic oxygen extraction ratio (all p > 0.1). Group 2, however, had a significantly lower cardiac index (CI), systemic oxygen consumption (VO2), and systemic oxygen delivery (DO2) (all p < 0.01). Systemic vascular resistance index (SVRI), initial and 6-h lactic acid levels were significantly higher in group 2 (all p < 0.03). CONCLUSIONS: The administration of all doses of epinephrine during the resuscitation of out-of-hospital cardiac arrest is associated with impairment of DO2 and VO2 in the postresuscitation period. Both duration and severity of these impairments correlate with the total cumulative epinephrine dose given during the resuscitation. Thus, inadvertent catecholamine toxicity represents a further complicating factor in the production of postresuscitation disease. Diagnostic and therapeutic interventions addressed toward mitigating these potentially reversible adverse effects may impact morbidity and mortality in out-of-hospital cardiac arrests.

Adult↗
PubMed1994

Effect of obesity on the clinical and hormonal characteristics of the polycystic ovary syndrome.

The polycystic ovary (PCO) syndrome is frequently associated with obesity. That subset of women reportedly shows a much higher incidence of hirsutism and menstrual irregularities than do nonobese women with PCO syndrome. We evaluated the clinical features and hormonal profiles of 56 women with PCO syndrome and correlated them with the presence or absence of obesity. Thirty-eight (67.8%) of these women were obese (body mass index > or = 25 kg/m2). While presenting with the classic manifestations of PCO, they did not differ significantly from the manifestations of nonobese women with PCO syndrome. Although obese women with PCO had a lower incidence of oligomenorrhea as compared to nonobese women with PCO (57.9% vs. 83.3%, respectively) and amenorrhea was more frequent in the former group (42.1% vs. 16.6%, respectively), these findings are not statistically significant. The incidences of hirsutism and anovulatory infertility in the obese group as compared to the nonobese group were 81.6% vs. 77.8% and 28.9% vs. 27.8%, respectively (not statistically significantly different). The mean (+/- SE) serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH ratios, prolactin and testosterone were not statistically significantly different among the two groups. The present study found that obesity is common in PCO syndrome but that there are no significant differences in the clinical and hormonal characteristics of obese and nonobese women with it. Further studies are warranted to clarify the impact of obesity on clinical, metabolic and hormonal changes in PCO syndrome.

Adult↗
PubMed1993

Kinetic and thermodynamic studies of the conversion of previtamin D3 to vitamin D3 in human skin.

The thermoisomerization of previtamin D3 to vitamin D3 is the last step in the synthesis of vitamin D3 in human skin. Kinetic and thermodynamic studies of this reaction in human skin and an organic solvent revealed that not only the equilibrium of the reaction was shifted in favor of vitamin D3 formation in human skin (equilibrium constant K at 37 degrees C = 11.44) compared to hexane (K = 6.15), but also the rate of the reaction was increased by more than 10-fold in human skin (T1/2 at 37 degrees C = 2.5 h) when compared to hexane (T1/2 = 30 30 h). This extraordinarily fast reaction rate was also confirmed in vitro in chicken skin and in vivo in human subjects. The enthalpy change for the reaction determined by the van't Hoff plot was delta H degree = -21.58 kJ mol-1 in human skin and delta H degree = -15.60 kJ mol-1 in hexane. Arrhenius plots showed that the activation energies for both the forward and the reverse reactions were lower in human skin (Ea1 = 71.05 kJ mol-1 and Ea2 = 92.63 kJ mol-1) than in hexane (Ea1 = 84.90 kJ mol-1 and Ea2 = 100.5 kJ mol-1). Activation parameters for the reaction in human skin and in hexane were also reported. Subcellular fractionation of human epidermal tissue revealed that most epidermal 7-dehydrocholesterol and previtamin D3 were in the membrane fraction, while only 20% were in the cytosol. The interaction of previtamin D3 with intracellular lipids and/or proteins in skin may be responsible for the increased vitamin D3 formation rate in the skin.

Adult↗
PubMed1993

On the potential role of proopiomelanocortin in skin physiology and pathology.

Pro-opiomelanocortin (POMC) is the precursor of ACTH, alpha-MSH and beta-endorphin, neuropeptides with multiple regulatory functions. Both the pituitary gland and peripheral tissues such as mammalian skin are capable of generating POMC-derived neuropeptides. Mammalian skin is also a target for POMC products; their possible roles in skin physiology and pathology are discussed in this communication.

Amino Acid Sequence↗
PubMed1993

Functional responses to extremely high plasma epinephrine concentrations in cardiac arrest.

OBJECTIVE: To evaluate the action of high-dose epinephrine by measuring simultaneously its vasopressor and norepinephrine releasing effects in humans during cardiac arrest. DESIGN: A prospective study on consecutive patients admitted with cardiac arrest. SETTING: Emergency Department in a large, urban hospital. PATIENTS: Eighteen patients with out-of-hospital cardiac arrest undergoing cardiopulmonary resuscitation (CPR). INTERVENTIONS: Catheterization of both the aorta and right atrium for the recording of pressure and collection of blood samples. Throughout the study period (12.5 mins), 18 patients received epinephrine at both the standard dose (1 mg, approximately 0.015 mg/kg) and high dose (0.2 mg/kg). Blood samples were drawn five times, every 2.5 mins. MEASUREMENTS AND MAIN RESULTS: Plasma epinephrine and norepinephrine concentrations; aorta, right atrial, and coronary perfusion pressures. Epinephrine concentrations (normal at rest = 160 +/- 10 [SEM] pmol/L) were increased at the time of the first sample (2.5 mins) by approximately 3,000-fold (to approximately 0.5 mumol/L), and, increased further to 12,000-fold (approximately 2.0 mumol/L) during the study. Aortic pressure increased from 20 +/- 3 to 28 +/- 3 mm Hg (p < .001), and coronary perfusion pressure increased from 4 +/- 3 to 10 +/- 3 mm Hg (p < .001). Simultaneous plasma norepinephrine concentrations were 30-fold higher than the normal resting value of 1.30 +/- 0.04 nmol/L, and increased by 90-fold during the study (p < .001). The spectral distributions of the individual correlations between plasma epinephrine and norepinephrine concentrations were segregated into high correlations (r > .83) in 12 of 18 patients and low r values (r = .29 to .79) in the remaining six patients. The distribution of the correlations was nonuniform by the Kolmogorov-Smirnov goodness-of-fit test with p < .001; this profile suggests that norepinephrine responsiveness to epinephrine can separate two populations, one of which (r > .83) would have preserved viability of the corresponding epinephrine receptors. The correlations between plasma epinephrine concentrations and coronary perfusion pressures were distributed more evenly, also in a nonuniform pattern (p < .02 by Kolmogorov-Smirnov goodness-of-fit test) and the relationship between the two sets of correlations was not significant. CONCLUSIONS: Despite the very high prevailing plasma epinephrine concentrations during cardiac arrest, further epinephrine increases still elicit biological responses. The present work provides physiologic support for the use of large doses of epinephrine during the course of CPR.

Adult↗
PubMed1993

A characterization of hypothalamic-pituitary-adrenal axis function during and after human cardiac arrest.

OBJECTIVE: This study characterizes hypothalamic-pituitary-adrenal axis function during cardiopulmonary arrest and after return of spontaneous circulation. DESIGN: Prospective case series. SETTING: A large urban emergency department and intensive care unit over an 8-month period. PATIENTS: Two hundred five adult patients presenting in cardiopulmonary arrest to an urban emergency department. Three patients known to be taking corticosteroids were excluded from the study. MEASUREMENTS AND MAIN RESULTS: Cortisol concentrations were measured before and after advanced cardiac life support and for five consecutive hours after return of spontaneous circulation. Adrenocorticotropic hormone (ACTH) concentrations were measured before advanced cardiac life support and when the cosyntropin stimulation tests were performed 6 and 24 hrs after the return of spontaneous circulation. The mean initial serum cortisol concentration was 32.0 +/- 33.1 micrograms/dL (882.9 +/- 913.2 nmol/L). Fifty-three percent of patients had cortisol concentrations of < 20 micrograms/dL (< 552 nmol/L) at the end of cardiac arrest. Among 44 patients who achieved return of spontaneous circulation, 98% had initial cortisol concentrations of > 10 micrograms/dL (> 276 nmol/L) and 73% of patients had initial cortisol concentrations of > 20 micrograms/dL (> 552 nmol/L). Mean serum cortisol concentrations increased significantly (p = .0001) from 1 to 6 hrs after return of spontaneous circulation and decreased significantly (p = .03) from 6 to 24 hrs. A serum cortisol concentration of < 30 micrograms/dL (< 828 nmol/L) was associated with a 96% and 100% mortality rate at 6 and 24 hrs, respectively. Mean ACTH concentrations were increased without a significant difference between the initial and 6-hr concentrations. Mean ACTH concentrations decreased between 6 and 24 hrs (p = .06). There were no significant responses to the cosyntropin stimulation at 6 and 24 hrs. CONCLUSIONS: Cortisol concentrations after out-of-hospital cardiac arrest are lower than those concentrations reported in other stress states. There is an association between cortisol concentrations and short-term survival after cardiac arrest. Survivors have a significantly greater increase in serum cortisol concentrations than nonsurvivors during the first 24 hrs. Lower than expected cortisol concentrations for the extreme stress of cardiac arrest may have pathologic significance in the hemodynamic instability seen after return of spontaneous circulation. The etiology of the low cortisol concentrations may be primary adrenal dysfunction.

Adrenocorticotropic Hormone↗
PubMed1993

Human plasma transport of vitamin D after its endogenous synthesis.

Transport of vitamin D3 from its sites of cutaneous synthesis into the circulation has been assumed to be via the plasma vitamin D binding protein (DBP). We studied vitamin D transport from the skin in seven healthy volunteers who received whole body irradiation with 27 mJ/cm2 dosage of ultraviolet B light (290-320 nm). Samples of venous blood were collected serially in EDTA and immediately chilled. In KBr, plasma samples were ultracentrifuged to provide a rapid separation of proteins of density < and > 1.3 g/ml. Upper and lower phases and serial fractions were analyzed for vitamin D3 (extraction, HPLC), cholesterol (enzyme assay), and human DBP (hDBP) (radial immunodiffusion). Total plasma vitamin D (basal level < 1 ng/ml) increased by 10 h and peaked at 24 h (9 +/- 1 ng/ml). 98% of the D3 remained at the density > 1.3 layers for up to 7 d, whereas cholesterol (> 85%) was detected at density < 1.3 and all of the hDBP was at density > 1.3. In three volunteers who each ingested 1.25 mg of vitamin D2, the total plasma D2 increased to 90 +/- 32 ng/ml by 4 h, and the D2 was evenly distributed between the upper and lower layers at 4, 8, and 24 h after the dose, indicating a continuing association of the vitamin with chylomicrons and lipoproteins, as well as with hDBP. Actin affinity chromatography removed D3 from plasma of irradiated subjects, indicating the association of the D3 with DBP. These findings indicate that endogenously synthesized vitamin D3 travels in plasma almost exclusively on DBP, providing for a slower hepatic delivery of the vitamin D and the more sustained increase in plasma 25-hydroxycholecalciferol observed after depot, parenteral administration of vitamin D. In contrast, the association of orally administered vitamin D with chylomicrons and lipoproteins allows for receptor-mediated, rapid hepatic delivery of vitamin D, and the reported rapid but less-sustained increases in plasma 25-hydroxycholecalciferol.

Adult↗
PubMed1993

Detection of proopiomelanocortin-derived antigens in normal and pathologic human skin.

We investigated the presence of proopiomelanocortin (POMC) products in sections of skin from normal subjects and patients with neoplastic and non-neoplastic cutaneous disorders. Antibodies specific against adrenocorticotropin, beta-melanotropin, and beta-endorphin were used for detection and characterization of cell types bearing POMC peptides. POMC products were not observed in sections of normal skin from the corporal (non-scalp) areas (six cases), whereas the hair follicles of scalp skin exhibited positive immunostains that were readily apparent (four cases). POMC products were frequently detected in corporal skin affected by diseases (13 of 26 cases), for example, psoriatic keratinocytes, the inflammatory infiltrate in scarring alopecia, nevocytes, the epithelial cell nests of basal cell carcinoma, and melanoma cells. Further tests were performed in keloids, a primary reactive skin disorder, to evaluate whether POMC accumulation represented a disease-related phenomenon or an expression of normal cutaneous reactivity. POMC products were consistently detected (10 of 11 cases) in the keratinocytes and mononuclear cells at keloid lesions. Thus these observations indicate that POMC products may accumulate locally in lesional skin representing, presumably, a novel cutaneous response to injury. The broad spectrum of POMC products detected suggests that these arise from production in situ (expression of the POMC gene itself) by human skin.

Adrenocorticotropic Hormone↗
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↗