Biomedical subjects
D A Goldstein
Publications and source records attributed to D A Goldstein.
Psychoneuroimmunology and HIV-1.
Recent psychoneuroimmunologic findings have suggested that it may be useful to evaluate the influence of behavioral factors on immune functioning and disease progression among human immunodeficiency virus-Type 1 (HIV-1) infected individuals. Behavioral interventions with immunomodulatory capabilities may help restore competence and thereby arrest HIV-1 disease promotion at the earliest stages of the infectious continuum. Evidence describing benefits of behavioral interventions such as aerobic exercise training on both psychological and immunological functioning among high-risk HIV-1 seronegative and very early stage seropositive gay men is presented. The HIV-1 infection is cast as a chronic disease for which early immunomodulatory behavioral interventions may have important physical and psychological impact.
Cardiovascular and neurohumoral responses to behavioral challenge as a function of race and sex.
Cardiovascular and hormonal responses to a structured interview, an electronic video game, a cold pressor test, and exercise on a bicycle ergometer were assessed in eighty-three 25- to 44-year-old normotensive Black and White men and women. Blacks showed significantly greater diastolic blood pressure (DBP) responses than Whites during the cold pressor test, which were not accounted for by an increase in plasma catecholamines. Exercise produced reliably greater systolic blood pressure (SBP) increases in Black women than in Black men or White women. Men showed significantly greater SBP and DBP changes than women during the video game. These findings suggest that the pattern of physiological reactivity elicited by challenge is related to the race and sex of the subjects.
Protein comparison and classification: a differential geometric approach.
A method is proposed for rapidly, quantitatively comparing protein structures of arbitrary sizes, based on the differential geometric representation. The method is applied to a group of 22 protein x-ray structures, and the resulting network of closest relationships is delineated. Several well-known fold types are automatically detected as groupings of related structures, even when the constituent proteins are of different lengths. A complete gradation of types is shown to be detected, ranging from all-helical to all-beta-structure proteins. A relationship among functionally similar proteins is shown in several cases, even where their three-dimensional structures differ. It is suggested that the positions of proteins within the network of relationships correspond with their folding mechanisms.
Birth defects following maternal exposure to ergotamine, beta blockers, and caffeine.
Ergotamine exposure during pregnancy has been suggested to cause birth defects which have a vascular disruptive aetiology. The present case provides additional support for the possible adverse fetal effects of exposure to ergotamine, caffeine, and propranolol during the first four months of pregnancy. At birth the infant showed evidence of early arrested cerebral maturation and paraplegia. The nature of these defects suggests a primary vascular disruptive aetiology. We hypothesise that ergotamine, acting either alone or in synergy with propranolol and caffeine, produced fetal vasoconstriction resulting in tissue ischaemia and subsequent malformation. This case raises the possibility that fetal malformation may result from concomitant use of multiple vasoconstrictive agents during pregnancy.
Hyperparathyroidism and hypotestosteronemia of acute renal failure.
Acute and chronic renal failure are associated with a marked reduction in the serum levels of testosterone. The mechanisms underlying this abnormality are unknown. Certain data have implicated the high blood levels of parathyroid hormone (PTH) of uremia in the genesis of the hypotestosteronemia. The effects of 3 days of acute uremia in dogs with intact parathyroid glands and in thyroparathyroidectomized animals on serum testosterone levels and on the calcium content of the hypothalamus, pituitary gland, and the testes were examined. Similar studies were performed in normal dogs treated with parathyroid extract for 3 days. The serum levels of testosterone were significantly (p less than 0.01) reduced, and the calcium levels of hypothalamus, pituitary gland, and testes were significantly (p less than 0.01) increased in the acutely uremic dogs with intact parathyroid glands and in the normal dogs treated with parathyroid extract. Prior parathyroidectomy in the acutely uremic dogs prevented these abnormalities. The results of our study assign an important role for the excess blood levels of PTH in uremia in the genesis of the hypotestosteronemia. The data suggest that the effect of excess PTH on serum testosterone levels may be mediated through the accumulation of calcium in the organs which participate in synthesis and/or release of testosterone.
Acute tricresylphosphate intoxication in childhood.
Tricresylphosphates (TCP) have been responsible for a large number of epidemic and individual intoxications since the recognition, in 1899, that phospho-creosote was the cause of paralysis in patients being treated for tuberculosis. Although children are mentioned as being among the victims of epidemic intoxication, no well documented reports of acute tricresylphosphate ingestion in childhood are available in the literature. We report a case of severe intoxication in a 4 1/2-year-old child following ingestion of a lubricant containing TCP. Clinical findings in this child were typical of previously reported acute ingestions in adults: acute gastro-intestinal symptoms, delayed cholinergic crisis and neurological toxicity. Previous literature is reviewed briefly and discussed.
Volume of distribution of phenytoin not altered in storage disease.
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Differential geometry and protein conformation. V. Medium-range conformational influence of the individual amino acids.
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Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers.
Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml X min-1 X 1.73 m-2. Peak plasma concentrations of 10-20 ng X ml-1 were obtained 1-3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
VDTs: is there a danger of radiation?
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Prognostic significance of short umbilical cord.
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Rhabdomyolysis and pancytopenia in a young man.
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The role of the student ward in the medical clerkships.
The authors describe the structure and the development of an internal medicine clerkship designed to promote proficiency in the process of clinical reasoning. The clerkship is centered around a "student ward" in which the student assumes the role of primary physician. The environment provides not only close supervision and counsel but also allows a great deal of autonomy as students embark on their first clinical medicine rotation. The student ward offers a structured environment where the emphasis is on in-depth clinical exposure and the acquisition of clinical knowledge in a manner consistent with the principles of problem-based learning. Breadth of clinical exposure is accomplished through a variety of educational approaches.
Role of parathyroid hormone in the glucose intolerance of chronic renal failure.
Evidence has accumulated suggesting that the state of secondary hyperparathyroidism and the elevated blood levels of parathyroid hormone (PTH) in uremia participate in the genesis of many uremic manifestations. The present study examined the role of PTH in glucose intolerance of chronic renal failure (CRF). Intravenous glucose tolerance tests (IVGTT) and euglycemic and hyperglycemic clamp studies were performed in dogs with CRF with (NPX) and without parathyroid glands (NPX-PTX). There were no significant differences among the plasma concentrations of electrolytes, degree of CRF, and its duration. The serum levels of PTH were elevated in NPX and undetectable in NPX-PTX. The NPX dogs displayed glucose intolerance after CRF and blood glucose concentrations during IVGTT were significantly (P less than 0.01) higher than corresponding values before CRF. In contrast, blood glucose levels after IVGTT in NPX-PTX before and after CRF were not different. K-g rate fell after CRF from 2.86 +/- 0.48 to 1.23 +/- 0.18%/min (P less than 0.01) in NPX but remained unchanged in NPX-PTX (from 2.41 +/- 0.43 to 2.86 +/- 0.86%/min) dogs. Blood insulin levels after IVGTT in NPX-PTX were more than twice higher than in NPX animals (P less than 0.01) and for any given level of blood glucose concentration, the insulin levels were higher in NPX-PTX than NPX dogs. Clamp studies showed that the total amount of glucose utilized was significantly lower (P less than 0.025) in NPX (6.64 +/- 1.13 mg/kg X min) than in NPX-PTX (10.74 +/- 1.1 mg/kg X min) dogs. The early, late, and total insulin responses were significantly (P less than 0.025) greater in the NPX-PTX than NPX animals. The values for the total response were 143 +/- 28 vs. 71 +/- 10 microU/ml, P less than 0.01. There was no significant difference in the ratio of glucose metabolized to the total insulin response, a measure of tissue sensitivity to insulin, between the two groups. The glucose metabolized to total insulin response ratio in NPX (5.12 +/- 0.76 mg/kg X min per microU/ml) and NPX-PTX (5.18 +/- 0.57 mg/kg X min per microU/ml) dogs was not different but significantly (P less than 0.01) lower than in normal animals (9.98 +/- 1.26 mg/kg X min per microU/ml). The metabolic clearance rate of insulin was significantly (P less than 0.02) reduced in both NPX (12.1 +/- 0.7 ml/kg X min) and NPX-PTX (12.1 +/- 0.9 ml/kg X min) dogs, as compared with normal animals (17.4 +/- 1.8 ml/kg X min). The basal hepatic glucose production was similar in both groups of animals and nor different from normal dogs; both the time course and the magnitude of suppression of hepatic glucose production by insulin were similar in both in groups. There were no differences in the binding affinity, binding sites concentration, and binding capacity of monocytes to insulin among NPX, NPX-PTX, and normal dogs. The data show that (a) glucose intolerance does not develop with CRF in the absence of PTH, (b) PTH does not affect metabolic clearance of insulin or tissue resistance to insulin in CRF, and (c) the normalization of metabolism in CRF in the absence of PTH is due to increased insulin secretion. The results indicate that excess PTH in CRF interferes with the ability of the beta-cells to augment insulin secretion appropriately in response to the insulin-resistant state.
Anaphylactic response to hydrocortisone in childhood: a case report.
Anaphylactic reactions to hydrocortisone have been well described in adults, but have not been reported in children. We wish to report such a reaction in a 6-year-old girl who had a positive intradermal reaction to methylprednisolone. Control subjects were non-reactive. Previous literature is briefly reviewed and discussed.
On the redox conformational change in cytochrome c.
The relationship between the crystal structures of oxidized and reduced tuna cytochrome c has been reexamined by a superposition method motivated by recent studies of the cytochrome c-cytochrome c peroxidase complex. It is shown that the observed structural changes precisely reflect the binding face suggested by chemical modification studies. It is further suggested that the large observed motion of lysine-27 and a smaller overall motion of the two binding edges constitute a redox binding-affinity switch and that the driving force for the conformational change of the protein is provided by the internal conformational change and charge redistribution of the heme, which cause it to tilt, under the influence of covalent and nonbonded interactions, within its protein envelope. A picture is presented of the molecule as an electron storage/transfer machine with three elements--a binding module, an electron storage module, and a conformational energy-storage module.
Production and partial purification of rat fibroblast-derived interferon induced in a newly established cell line.
Interferon (IFN) production induced by either Newcastle disease virus (NDV) or Sendai virus was compared in 10 different rat cell lines. Although there was variation in the IFN titers produced, NDV proved to be the best inducer in each cell line with optimum IFN yields occurring with a multiplicity of infection (MOI) of 1.0. A new continuous rat fibroblast cell line (CD) produced high titers of IFN similar to those reported for other high producers; while Ratec cells were shown to be the most sensitive to the antiviral activity of rat IFN. Partial purification and characterization of IFN produced in CD cells was accomplished by column chromatography. Four sorbents with varying modes of action for binding the IFN (Affi-Gel 202, Poly(U)-Sepharose 4B, CM-Sepharose CL-6B, and Phenyl-Sepharose CL-4B) were compared. The Phenyl-Sepharose CL-4B matrix proved to be the most successful for purification of rat IFN; one passage through this column, increased the specific activity more than 100-fold, with a concomitant recovery of 90%-95% biologic activity. The binding characteristics of rat IFN on each of the column matrices, however, demonstrated differences between the physicochemical nature of CD rat IFN and murine and hamster IFNs.