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Biomedical subjects

R Rosenfeld

Publications and source records attributed to R Rosenfeld.

At least 91 records · Page 5Linked to original sources

Glomus vagale tumors.

Eighteen patients with glomus vagale tumors treated by surgical resection are reviewed. Computed tomography and magnetic resonance imaging are diagnostic. Arteriography is used to determine multicentric tumors. The incidence of multicentric tumors in this series was 40%. Adequate surgical exposure is necessary for removal of the tumor without injury to the carotid artery. Vagal paralysis was present in all cases postoperatively and resulted in dysphagia and aspiration. Cricopharyngeal myotomy and Teflon injection aided in rehabilitation of deglutition. Curability with surgery is high, but radiation therapy is recommended in selected patients.

Adult↗

Evidence that type II insulin-like growth factor receptor is coupled to calcium gating system.

In competent Balb/c 3T3 cells primed with epidermal growth factor (primed competent cells), insulin-like growth factor-II (IGF-II) stimulated calcium influx in a concentration dependent manner with the ED50 of 450 pM. When receptor-bound [125I]IGF-II was cross-linked by use of disuccinimidyl suberate, a 240 K-Da protein was radiolabeled. Excess amount of unlabeled IGF-II inhibited the affinity-labeling of the 240 K-Da protein. To further examine whether IGF-II stimulates calcium influx by acting on the type II IGF receptor, we employed polyclonal antibody raised against rat type II IGF receptor, R-II-PABl. This antibody immunoprecipitated the type II IGF receptor and inhibited IGF-II binding in Balb/c 3T3 cell membrane without affecting IGF-I binding. In primed competent cells, R-II-PABl elicited an agonistic action in stimulating [3H]thymidine incorporation. Under the same condition, R-II-PABl elicited a marked stimulation of calcium influx. These results suggest that, in Balb/c 3T3 cells, 1) relatively low concentrations of IGF-II act mainly on the type II IGF receptor; 2) the type II IGF receptor is coupled to a calcium gating system; and 3) binding of a ligand to the type II IGF receptor leads to the stimulation of DNA synthesis.

Animals↗

Enzymes of the contact phase of blood coagulation: kinetics with various chromogenic substrates and a two-substrate assay for the joint estimation of plasma prekallikrein and factor XI.

Kinetic constants (Km and kcat) of kallikrein and factor XIa for the chromogenic substrates H-D-L-prolyl-L-phenylanyl-L-arginine-p-nitroanilide (S-2302) and L-pyroglutamyl-L-propyl-L-arginine-p-nitroanilide (S-2366) were determined. The determined constants allow the use of S-2302 and S-2366 in an assay that leads to the joint estimation of factor XI and prekallikrein in activated plasma. The assay reports approximately 3.1 micrograms/ml factor XIa and 34.5 micrograms/ml kallikrein in kaolin-activated plasma (kaolin content 2 mg/ml). The dual-substrate amidolytic assay shows good correlation with the coagulant assay of both factors (0.92 with the prekallikrein assay and 0.98 with the factor XI assay). It is capable, through the joint estimation of factor XI and prekallikrein levels, of differentiating among plasma samples deficient in components of the contact phase of blood coagulation. Kinetic constants of factor beta-XIIa (factor XII fragment) for these substrates and for N-benzol-L-isoleusyl-L-glutamyl-glycyl-L-arginine-P-nitro ani lide (S-2222) were determined, and they allowed the assessment of the contribution of this factor to this assay and its estimation in the activated phase.

Blood Coagulation↗

Effects of chemical modifications on the surface- and protein-binding properties of the light chain of human high molecular weight kininogen.

The light chain of kallikrein-cleaved human high molecular weight kininogen is solely responsible for its cofactor activity in blood clotting. Sequencing of the NH2-terminal region of the light chain reported herein identified the third kallikrein cleavage site of high molecular weight kininogen as Arg-437. The co-factor activity of high molecular weight kininogen consists of the capacity to bind to negatively charged surfaces and to factor XI or prekallikrein. Chemical modification of the histidines by either photooxidation or ethoxyformic anhydride affected the equivalent of 14-16 of 23 histidines available and resulted in over 90% loss in procoagulant activity. The modified protein had drastically reduced surface- and zinc-binding capacity, but it bound successfully to either factor XI or prekallikrein. In contrast, modification of two carboxyl groups, which led to approximately 80-90% loss of procoagulant activity, seriously compromised protein binding but left surface binding unaffected. All 3 tryptophans were modified at pH 4.0 with N-bromosuccinimide with a 70% reduction in procoagulant activity, but only 1 tryptophan was available for reaction at pH 7.35, resulting in a 50% loss in activity. Tryptophan modification at acidic pH affected protein binding but did not modify surface or zinc binding. Modification of both available tyrosine and 9 of 18 available lysine residues did not have a significant effect on the procoagulant activity of the light chain. These studies indicate that histidines participate in surface binding and that free carboxyl groups and tryptophan side chains are involved in binding of high molecular weight kininogen to other clotting factors.

Amino Acid Sequence↗

Fluvoxamine treatment of obsessive-compulsive disorder.

Sixteen outpatients who met DSM-III criteria for obsessive-compulsive disorder completed a 20-week double-blind, crossover trial with fluvoxamine and placebo. Thirteen (81%) improved with fluvoxamine, while three (19%) improved with placebo. Fluvoxamine treatment was associated with significant improvement on measures of obsessive-compulsive symptoms, anxiety, and depression. Depressed subjects' improvement on obsessive-compulsive measures correlated with improvement in symptoms of depression. Nondepressed subjects also showed improvement on measures of obsessive-compulsive symptoms. In this trial, fluvoxamine was an effective and safe treatment for obsessive-compulsive disorder.

Adolescent↗

Adjusting for baseline measurements in the two-period crossover study: a cautionary note.

It is intuitively appealing in planning a two-period crossover study to have each patient measured on the response variable at the beginning as well as at the end of both periods, and to take the change from the value at the start of the period to the value at the end as the measure of the patient's response to the treatment given during that period. This apparently innocuous procedure may, contrary to one's intuition, produce bias in the analysis of the data for a difference between the residual effects and a difference between the direct treatment effects.

Epidemiologic Methods↗

Smith-Lemli-Opitz syndrome in two 46,XY infants with female external genitalia.

Two infants with features of the Smith-Lemli-Opitz (SLO) syndrome were found to have a 46,XY karyotype and female external genitalia. Autopsies showed normal testes for age with normal Wolffian duct structures and without Müllerian duct derivatives. This failure of masculinization of the external genitalia is an unusual finding and may represent the extreme of a spectrum of the genital anomalies commonly seen in males with this autosomal recessive syndrome. An endocrine evaluation on one of these infants at 3 months suggested unusually low testosterone production and meagre response to stimulation with human chorionic gonadotropin (hCG). The failure of complete masculinization of external genitalia in some cases of SLO syndrome may be due to inadequate testosterone production in utero.

Abnormalities, Multiple↗

Chlorpromazine excretion by the neonate following chronic in utero exposure.

The pharmacokinetics of chlorpromazine in the newborn have not been reported. We studied the kinetics of removal of chlorpromazine from plasma in an infant whose mother was treated with high doses of chlorpromazine and lithium throughout the last trimester of pregnancy. The infant exhibited symptoms of severe neurologic depression that slowly abated over the first 9 days of life. The kinetics of plasma chlorpromazine removal were described with a two-compartment model, exhibiting a rapid half-life of 1.46 days and a slow half-life of 3.19 days. Both half-lives are considerably longer than the rapid and slow half-lives described in adults. Caution in exposing the fetus or newborn to chlorpromazine is warranted. Further information on the distribution and excretion of chlorpromazine by the newborn is needed.

Adult↗

Factors related to orthostatic hypotension associated with tricyclic antidepressants.

A group of 45 depressed patients treated with imipramine hydrochloride were examined in an attempt to identify factors that might influence the risk of developing orthostatic hypotension. Although the literature suggests that age and/or heart disease influences the occurrence of orthostatic hypotension, these conclusions are controversial. To pursue this issue, a sample of older depressed patients, many with severe cardiovascular disease, was chosen. The incidence of orthostatic hypotension rose dramatically among those with severe heart disease. There was a significant association between symptomatic orthostatic hypotension and cardiac medication (p less than .01), and trends between orthostatic hypotension and both ejection fraction (p = .11) and baseline forearm resistance (p = .16). The sample is too small to permit determination of the relative independent importance of these variables or the contribution of specific cardiovascular drugs among these sicker cardiac patients.

Aged↗

Sacrococcygeal tumour in infancy.

A newborn infant delivered after 33 1/2 weeks' gestation was operated on for sacrococcygeal teratoma. This tumour contained an unusual intra-abdominal cystic component that caused pulmonary problems. Amniography and echography were useful for diagnosing this lesion in utero.

Adult↗

Geographic constraints on women's careers in academia.

Male and female academics have very different residence patterns. Women are more concentrated in our largest urban centers; also, wherever they reside, women are less likely than men to change communities when changing institutions. Much of this sex difference is attributable to the constraints under which married academic women must manage their careers, in particular the requirements of two-career households. The authors argue that the status difference between men and women in academia is attributable, in part, to the geographic limitations on the locations of married women, as these prevent making strategic job changes to advance career prospects.

Career Mobility↗