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Biomedical subjects

R E Goldstein

Publications and source records attributed to R E Goldstein.

At least 37 records · Page 2Linked to original sources
PubMed1999

Insulin- and glucagon-independent effects of calcitonin gene-related peptide in the conscious dog.

Calcitonin gene-related peptide (CGRP) causes vasodilation in many vascular beds, resulting in hypotension and tachycardia. The current studies were conducted in overnight-fasted conscious dogs to determine the effect of different CGRP dosages on carbohydrate metabolism and catecholamine release resulting from hemodynamic changes. During a pancreatic clamp, dogs received intraportal infusions of CGRP at 13, 26, and 52 (n = 3) or 52, 105, and 210 pmol x kg(-1) x min(-1) (n = 4; 60 minutes at each rate). Blood pressure decreased (P < .05) and the heart rate and hepatic blood flow (HBF) increased a maximum of 100% and 30%, respectively (P < .05). For the five CGRP infusion rates, arterial plasma epinephrine increased approximately 1.3-, 2.4-, 7.4-, 12-fold, and eightfold basal, respectively; norepinephrine increased about 2.3-, 3.3-, 4.1-, 4.6-, and 4.8-fold basal, respectively; and cortisol increased about twofold, 3.4-fold, fivefold, sixfold, and 6.2-fold basal, respectively. At CGRP infusion rates of 52 pmol x kg(-1) x min(-1) or higher, increases (P < .05) occurred for plasma glucose, endogenous glucose production (EndoRa), and net hepatic uptake of gluconeogenic substrates (maximum change, 24 mg/dL, 1.3 mg x kg(-1) x min(-1), and 9.9 micromol x kg(-1) x min(-1), respectively). Arterial blood glycerol concentrations increased only a maximum of 30%. At the two highest CGRP infusion rates, glycerol returned to basal concentrations and arterial plasma nonesterified fatty acids (NEFAs) decreased. The increased net hepatic uptake of gluconeogenic substrates during CGRP infusion was sufficient to account for 49% to 58% of the increase in EndoRa. CGRP has no apparent direct effects on hepatic carbohydrate metabolism, but the catecholamines, at levels similar to those observed during CGRP infusion, stimulate hepatic glycogenolysis. Therefore, some factor(s) other than CGRP, probably an increase in circulating catecholamine concentrations, would appear to be responsible for at least 42% to 51% of the increase in EndoRa.

Alanine↗
PubMed1999

Clinical experience over 48 years with pheochromocytoma.

OBJECTIVE: To analyze the presentation, localization, surgical management, pathology, and long-term outcome of a large series of patients with pheochromocytomas. SUMMARY BACKGROUND DATA: There are several areas of controversy pertaining to pheochromocytomas. Although many studies report a higher rate of malignancy for extraadrenal pheochromocytomas than for adrenal pheochromocytomas, the number of patients with the former tumor are small and statistical analysis is lacking. There has also been recent debate as to whether microscopic features of the tumor may be predictive of future behavior. METHODS: From 1950 to 1998, the authors observed 108 pheochromocytomas in 104 patients. The outcome of these patients has been followed prospectively. The medical records of these patients were reviewed for data on the presentation, localization, surgical management, pathology, and outcome. Patient survival was analyzed using Kaplan-Meier survival distributions. RESULTS: This study included 66 female patients and 38 male patients. The average age at surgery was 42.3 years. Sporadic cases accounted for 84% of the patients; the other 16% had multiple endocrine neoplasia type 2, von Recklinghausen's disease, von Hippel-Lindau disease, or Carney's syndrome. Of 64 adrenal tumors, 55 were initially considered benign, 6 had microscopic malignant features, and 3 had malignant disease. Mean patient follow-up was 12.6 years. To date, in five additional patients (none with microscopic disease) malignant disease developed (13% overall rate of malignancy). Recurrence occurred as late as 15 years after resection. Of 26 extraadrenal pheochromocytomas, 14 were initially considered benign, 8 had microscopic malignant features, and 4 had malignant disease. Thus, 46% of patients had either malignant disease or tumors with malignant features. Mean patient follow-up was 11.5 years. In one patient with benign disease and in one patient with malignant features, malignant disease developed (23% overall rate of malignancy). The difference in the rate of malignancy was not statistically significant between adrenal and extraadrenal pheochromocytomas. Patients with adrenal and extraadrenal pheochromocytomas also had similar rates of survival (p = NS). CONCLUSIONS: The data suggest that patients with extraadrenal pheochromocytomas have the same risk of malignancy and the same overall survival as patients with adrenal pheochromocytomas. Lifelong follow-up of these patients is mandatory.

Adolescent↗
PubMed1999

Huckebein repressor activity in Drosophila terminal patterning is mediated by Groucho.

The Groucho corepressor mediates negative transcriptional regulation in association with various DNA-binding proteins in diverse developmental contexts. We have previously implicated Groucho in Drosophila embryonic terminal patterning, showing that it is required to confine tailless and huckebein terminal gap gene expression to the pole regions of the embryo. Here we reveal an additional requirement for Groucho in this developmental process by establishing that Groucho mediates repressor activity of the Huckebein protein. Putative Huckebein target genes are derepressed in embryos lacking maternal groucho activity and biochemical experiments demonstrate that Huckebein physically interacts with Groucho. Using an in vivo repression assay, we identify a functional repressor domain in Huckebein that contains an FRPW tetrapeptide, similar to the WRPW Groucho-recruitment domain found in Hairy-related repressor proteins. Mutations in Huckebein's FRPW motif abolish Groucho binding and in vivo repression activity, indicating that binding of Groucho through the FRPW motif is required for the repressor function of Huckebein. Taken together with our earlier results, these findings show that Groucho-repression regulates sequential aspects of terminal patterning in Drosophila.

Amino Acid Motifs↗
PubMed1999

The current status of vital tooth whitening techniques.

Tooth whitening of vital teeth continues to have a major impact on the practice of dentistry. The growing public interest in having whiter, brighter teeth is clearly evident in the advertisements from toothpaste manufacturers on "whitening" formulations of their products and by the number of individuals seeking whitening procedures from their dentists. In addition, new over-the-counter whitening products continue to emerge in a marketplace that cannot seem to get teeth white enough, bright enough, fast enough. What new products and procedures have evolved over the past decade to whiten teeth? Are they better, safer, faster, and more effective now? Are dentists meeting public demand for whiter teeth and is this quest having a positive or negative impact on the practice of dentistry or the patient's dental health? I posed these questions to a group of experts on whitening procedures to get their opinions and recommendations.

Anti-Bacterial Agents↗
PubMed1999

Plasma amino acid profiles in cats with naturally acquired chronic renal failure.

OBJECTIVE: To characterize potential changes in preprandial plasma amino acid concentrations in cats with naturally acquired chronic renal failure (CRF), compared with healthy cats, and to assess potential effects of the severity of renal failure on plasma amino acid concentrations in these cats. ANIMALS: 62 adult cats. PROCEDURE: Preprandial plasma amino acid concentrations were evaluated in 38 cats with mild, moderate, or severe CRF and in 24 apparently healthy cats. Effects of severity of renal failure, amount of dietary protein, degree of weight loss, appetite, and body condition on plasma amino acid profiles were evaluated. RESULTS: Cats with various stages of CRF had significantly (P< 0.05) decreased plasma concentrations of o-hydroxyproline, glutamate, proline, glycine, alanine, tyrosine, tryptophan, and arginine, and significantly increased plasma concentrations of asparagine, citrulline, ornithine, 1-methylhistidine, and 3-methylhistidine. Significant (P < 0.05) alterations in amino acid concentrations also were identified when cats with CRF were grouped by appetite or severity of renal disease. Amount of dietary protein, body condition, or degree of weight loss had no significant effect on plasma amino acid concentrations. CONCLUSIONS: Compared with those in healthy cats, preprandial plasma amino acid profiles in cats with mild, moderate, or severe CRF are abnormal. CLINICAL RELEVANCE: Despite frequency of altered plasma amino acid concentrations in cats with CRF, the magnitude of these changes is mild and of little clinical relevance. Short-term use of a commercial protein-restricted diet has no deleterious effects on plasma amino acid concentrations.

Amino Acids↗
PubMed1998

Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.

The mammalian AML/CBFalpha runt domain (RD) transcription factors regulate hematopoiesis and osteoblast differentiation. Like their Drosophila counterparts, most mammalian RD proteins terminate in a common pentapeptide, VWRPY, which serves to recruit the corepressor Groucho (Gro). Using a yeast two-hybrid assay, in vitro association and pull-down experiments, we demonstrate that Gro and its mammalian homolog TLE1 specifically interact with AML1 and AML2. In addition to the VWRPY motif, other C-terminal sequences are required for these interactions with Gro/TLE1. TLE1 inhibits AML1-dependent transactivation of the T cell receptor (TCR) enhancers alpha and beta, which contain functional AML binding sites, in transfected Jurkat T cells. LEF-1 is an additional transcription factor that mediates transactivation of TCR enhancers. LEF-1 and its Drosophila homolog Pangolin (Pan) are involved in the Wnt/Wg signaling pathway through interactions with the coactivator beta-catenin and its highly conserved fly homolog Armadillo (Arm). We show that TLE/Gro interacts with LEF-1 and Pan, and inhibits LEF-1:beta-catenin-dependent transcription. These data indicate that, in addition to their activity as transcriptional activators, AML1 and LEF-1 can act, through recruitment of the corepressor TLE1, as transcriptional repressors in TCR regulation and Wnt/Wg signaling.

Amino Acid Sequence↗
PubMed1998

Gastrin concentrations in plasma of cats with chronic renal failure.

OBJECTIVE: To determine the prevalence of hypergastrinemia in cats with naturally developing chronic renal failure (CRF) and the correlation between gastrin concentration in plasma and severity of CRF. DESIGN: Cohort study. ANIMALS: 30 cats with naturally developing CRF and 12 clinically normal control cats. PROCEDURE: Gastrin concentrations in plasma were determined by double-antibody radioimmunoassay of blood samples obtained from cats after food was withheld 8 hours. Concentrations were compared, using a nonparametric Kruskal-Wallis ANOVA. RESULTS: 18 cats with CRF had high gastrin concentrations (median, 45 pg/ml; range, < 18 to > 1,333 pg/ml), compared with those for control cats (< 18 pg/ml). Prevalence of hypergastrinemia increased with severity of renal insufficiency. Three of 9 cats with mild CRF, 6 of 11 cats with moderate CRF, and 9 of 10 cats with severe CRF had high gastrin concentrations. Gastrin concentrations were significantly different between control cats and cats with CRF, regardless of disease severity. CLINICAL IMPLICATIONS: The potential role of high concentrations of gastrin on gastric hyperacidity, uremic gastritis, bleeding from the gastrointestinal tract, and associated clinical signs of hypergastrinemia (e.g., anorexia and vomiting) may justify use of histamine2-receptor antagonists or proton pump inhibitors to suppress gastric acid secretion in cats with CRF that have these clinical signs.

Animals↗
PubMed1998

Trapping and wiggling: elastohydrodynamics of driven microfilaments.

We present an analysis of the planar motion of single semiflexible filaments subject to viscous drag or point forcing. These are the relevant forces in dynamic experiments designed to measure biopolymer bending moduli. By analogy with the "Stokes problems" in hydrodynamics (motion of a viscous fluid induced by that of a wall bounding the fluid), we consider the motion of a polymer, one end of which is moved in an impulsive or oscillatory way. Analytical solutions for the time-dependent shapes of such moving polymers are obtained within an analysis applicable to small-amplitude deformations. In the case of oscillatory driving, particular attention is paid to a characteristic length determined by the frequency of oscillation, the polymer persistence length, and the viscous drag coefficient. Experiments on actin filaments manipulated with optical traps confirm the scaling law predicted by the analysis and provide a new technique for measuring the elastic bending modulus. Exploiting this model, we also present a reanalysis of several published experiments on microtubules.

Actin Cytoskeleton↗
PubMed1998

Protein turnover and energy expenditure increase during exogenous nutrient availability in sickle cell disease.

In the present study, energy expenditure (EE) and rates of whole-body protein, glucose, and lipid metabolism were assessed in 8 African American sickle cell disease (SCD) patients and in 6 healthy African American control subjects during the infusion of amino acids, glucose, and lipid. Whole-body protein, glucose, and lipid kinetics were estimated by using L-[1-(13)C]leucine, D-[6,6-(2)H2]glucose, and [(2)H5]glycerol, respectively. After a 2-h tracer equilibration period and a 0.5-h basal period, nutrients were administered intravenously for 3 h with 16% of the energy as protein, 52% as carbohydrate, and 32% as fat. Breath and blood were collected during the last 30 min of nutrient infusion and EE was measured by indirect calorimetry. EE was 14% greater (P < or = 0.05) in SCD patients [145.0 +/- 3.5 kJ x kg fat-free mass (FFM)(-1) x d(-1)] than in control subjects (126.8 +/- 3.8 kJ x kg FFM(-1) x d(-1)). Whole-body protein breakdown (4.4 +/- 0.4 compared with 3.1 +/- 0.1 mg x kg FFM(-1) x min(-1), P < or = 0.05) and protein synthesis (4.6 +/- 0.4 compared with 3.2 +/- 0.1 g x kg FFM(-1) x min(-1), P < or = 0.05) were 42% and 44% greater, respectively, in the SCD patients than in control subjects, but whole-body amino acid oxidation (0.90 +/- 0.05 compared with 1.03 +/- 0.09 mg x kg FFM(-1) x min(-1)) was not significantly different between the 2 groups. Whole-body glucose and lipid kinetics did not differ significantly between the groups. EE increased in SCD patients during exogenous nutrient availability, and the additional energy required for the accelerated rates of whole-body protein breakdown and synthesis made a significant contribution to the increase in EE. These metabolic aberrations may increase the dietary energy and protein requirements of SCD patients.

Adult↗
PubMed1998

Issues in esthetic dentistry for older adults.

Esthetic dentistry offers a myriad of opportunities for older adults wishing to improve their smile, oral function, and self-esteem. The challenge for dental professionals is to maintain oral health throughout the patient's lifetime, even through periods of dependence that may include residence in a nursing home. Dental professionals will have increasing opportunities to share their knowledge and expertise about the relation between oral health and overall health, with a variety of health professionals who care for the aging population.

Aged↗
PubMed1998

Alterations in basal nutrient metabolism increase resting energy expenditure in sickle cell disease.

Basal rates of whole body protein, glucose, and lipid metabolism and resting energy expenditure (REE) were measured in eight African-American sickle cell disease (SCD) patients and in six African-American controls. Catheters were placed 1) in an antecubital vein for stable isotope infusion and 2) in a heated hand vein for arterialized venous blood. Breath and blood were collected during the last 30 min of the 2.5-h study, and REE was measured by indirect calorimetry. REE [128 +/- 5 vs. 111 +/- 1 kJ.kg fat-free mass (FFM)-1.day-1; P < 0.05 vs. controls] was 15% greater in the SCD patients. Whole body protein breakdown (5.0 +/- 0.3 vs. 3.8 +/- 0.2 mg.kg FFM-1.min-1; P < 0.05 vs. controls) and protein synthesis (4.4 +/- 0.3 vs. 3.2 +/- 0.2 mg.kg FFM-1.min-1; P < 0.05 vs. controls) were 32 and 38% greater, respectively, in the SCD patients, but whole body amino acid oxidation was similar (0.58 +/- 0.03 vs. 0.66 +/- 0.03 mg.kg FFM-1.min-1). Measures of whole body glucose and lipid metabolism were not significantly different between the groups. The additional energy required for the greater rates of whole body protein breakdown and synthesis caused by SCD contributes significantly to the observed increase in REE, suggesting that dietary energy and protein requirements are enhanced in SCD patients.

Adolescent↗
PubMed1997

Selection for spiral waves in the social amoebae Dictyostelium.

Starving Dictyostelium amoebae emit pulses of the chemoattractant cAMP that are relayed from cell to cell as circular and spiral waves. We have recently modeled spiral wave formation in Dictyostelium. Our model suggests that a secreted protein inhibitor of an extracellular cAMP phosphodiesterase selects for spirals. Herein we test the essential features of this prediction by comparing wave propagation in wild type and inhibitor mutants. We find that mutants rarely form spirals. The territory size of mutant strains is approximately 50 times smaller than wild type, and the mature fruiting bodies are smaller but otherwise normal. These results identify a mechanism for selecting one wave symmetry over another in an excitable system and suggest that the phosphodiesterase inhibitor may be under selection because it helps regulate territory size.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Clinical implications of silent versus symptomatic exercise-induced myocardial ischemia in patients with stable coronary disease.

OBJECTIVES: This study was undertaken to better understand the functional and prognostic significance of silent relative to symptomatic ischemia. BACKGROUND: Previous studies have reached conflicting conclusions as to whether painless ischemia identified during noninvasive cardiac testing is related to a lesser extent of myocardial ischemia or a different prognosis than ischemia accompanied by angina, or both. METHODS: Nine hundred thirty-six clinically stable patients 1 to 6 months after an acute coronary event, either myocardial infarction or unstable angina, underwent ambulatory monitoring, exercise treadmill testing and stress thallium-201 scintigraphy. They were then followed up prospectively for a mean of 23 months for recurrent cardiac events (cardiac death, nonfatal myocardial infarction or unstable angina). RESULTS: Compared with patients with symptomatic ischemia during testing (n = 125), those with silent ischemia (n = 378) demonstrated less severe and extensive reversible defects on stress thallium scintigraphy (p = 0.0008), less functional impairment during treadmill testing manifested by longer exercise duration (640 +/- 173 vs. 529 +/- 190 s, p = 0.002) and longer time to ST segment depression (530 +/- 215 vs. 419 +/- 205 s, p = 0.0001) and less frequent ST segment depression during ambulatory monitoring (9% vs. 19%, p = 0.005). Patients with symptomatic ischemia had a significantly (p = 0.004) increased number of subsequent recurrent cardiac events (28.8%) versus those with silent (18.0%) or no (17.3%) ischemia. Adverse outcomes were especially concentrated in the subgroup with symptomatic ischemia and poor exercise tolerance. The difference in cardiac event rates between patients with silent versus symptomatic ischemia persisted after adjustment for baseline clinical characteristics by Cox regression analysis. CONCLUSIONS: Patients with painless ischemia during exercise testing 1 to 6 months after recovery from a coronary event have less jeopardized ischemic myocardium and fewer recurrent cardiac events than patients with symptomatic ischemia.

Adult↗
PubMed1997

Laparoscopic adrenalectomy. A new standard of care.

OBJECTIVE: The authors review their experience with laparoscopic adrenalectomy in patients with benign adrenal neoplasms. Efficacy, safety, and cost effectiveness of the procedure are examined. BACKGROUND: Laparoscopic adrenalectomy is replacing open adrenalectomy in some medical centers as the standard surgical approach for uncomplicated tumors. However, laparoscopic adrenalectomy often is considered more difficult and more expensive than traditional "open" surgery. METHODS: Perioperative and postoperative records as well as hospital charges from the first 19 patients undergoing laparoscopic unilateral adrenalectomies at the authors' medical institutions were examined and compared with 19 patients who underwent open unilateral adrenalectomies. RESULTS: None of the 19 patients undergoing unilateral laparoscopic adrenalectomy required conversion to open adrenalectomy. Mean operative times as well as total hospital charges were similar in those patients undergoing either laparoscopic or open adrenalectomy. However, the morbidity and postoperative length of hospital stay were significantly less in those patients undergoing laparoscopic adrenalectomy. CONCLUSIONS: Laparoscopic adrenalectomy can be performed safety and with the benefits associated with minimally invasive surgery. In addition, the procedure is cost effective. These factors suggest that laparoscopic adrenalectomy should be the preferential surgical technique for benign adrenal disease.

Adrenal Gland Neoplasms↗
PubMed1997

In-office bleaching: where we came from, where we are today.

Discolored teeth are the primary aesthetic concern among dental patients. While many seek professional advice and treatment, an alarming number opt for non-professional quick-fix solutions. The in-office bleaching modality often is overlooked in favor of at-home vital bleaching. But this option has been proven to be effective, quick and safe-either alone or in combination with other aesthetic treatments-as a method of brightening and enhancing a patient's smile.

Anti-Bacterial Agents↗