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Biomedical subjects

D Goldfarb

Publications and source records attributed to D Goldfarb.

At least 55 records · Page 3Linked to original sources
PubMed1993

A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells.

Permissiveness of the host cell to productive infection by oncoretroviruses is cell-cycle dependent, and nuclear localization of viral nucleoprotein preintegration complexes will occur only after cells have passed through mitosis. In contrast, establishment of an integrated provirus after infection by the lentivirus HIV-1 is independent of host cell proliferation. The ability of HIV-1 to replicate in non-dividing cells is partly accounted for by the karyophilic properties of the viral preintegration complex which, after virus infection, is actively transported to the host cell nucleus. Here we report that the gag matrix protein of HIV-1 contains a nuclear localization sequence which, when conjugated to a heterologous protein, directs its nuclear import. In addition, HIV-1 mutants containing amino-acid substitutions in this nuclear localization signal integrate and replicate within dividing but not growth-arrested cells, and thus display a phenotype more representative of an oncoretrovirus.

Amino Acid Sequence↗
PubMed1993

Regulation of RNA processing and transport by a nuclear guanine nucleotide release protein and members of the Ras superfamily.

The RCC1 gene of mammals encodes a guanine nucleotide release protein (GNRP). RCC1 and a homolog in Saccharomyces cerevisiae (MTR1/PRP20/SRM1) have previously been implicated in control of mRNA metabolism and export from the nucleus. We here demonstrate that a temperature-sensitive fission yeast mutant which has a mutation in a homologous gene, and two of three additional (mtr1/prp20/srm1) mutants accumulate nuclear poly(A)+ RNA at 37 degrees C. In S.cerevisiae, maturation of rRNA and tRNA is also inhibited at 37 degrees C. Nevertheless, studies with the corresponding BHK-21 cell mutant indicate that protein import into the nucleus continues. MTR1 homologs regulate RNA processing at a point which is distinct from their regulation of chromosome condensation since: (i) poly(A)+ RNA accumulation in the fission yeast mutant precedes chromosome condensation, and (ii) unlike chromosome condensation, accumulation of nuclear poly(A)+ RNA does not require p34cdc28 kinase activation or protein synthesis. Moreover, experiments involving inhibition of DNA synthesis indicate that the S.cerevisiae homolog does not govern cell cycle checkpoint control. Since RCC1p acts as GNRP for Ran, a small nuclear GTPase of the ras superfamily, we have identified two homologs of Ran in S.cerevisiae (CNR1 and CNR2). Only CNR1 is essential, but both code for proteins extremely similar to Ran and can suppress mtr1 mutations in allele-specific fashion. Thus, MTR1 and its homologs appear to act as GNRPs for a family of conserved GTPases in controlling RNA metabolism and transport. Their role in governing checkpoint control appears to be restricted to higher eukaryotes.

Amino Acid Sequence↗
PubMed1993

Efficacy of herbal tea preparation in infantile colic.

We evaluated the effect of an herbal tea preparation on infantile colic in a prospective double-blind study. The use of tea eliminated the colic in 19 (57%) of 33 infants, whereas placebo was helpful in only 9 (26%) of 35 (p < 0.01). The mean colic score was significantly improved in tea-treated infants. No significant differences were noted between groups regarding number of night wakings.

Beverages↗
PubMed1992

Microinjected U snRNAs are imported to oocyte nuclei via the nuclear pore complex by three distinguishable targeting pathways.

The inhibitory effects of wheat germ agglutinin and mAb 414 on the nuclear import of all types of U snRNAs indicate that they cross the nuclear envelope through the nuclear pore complex. However, the import of different U snRNAs occurs by kinetically distinct targeting pathways that can be distinguished from one another by the competitive effects of free trimethylguanosine cap dinucleotide (m3GpppG) and P(Lys)-BSA, an efficient synthetic karyophile based on the nuclear localization signal of SV40 large T antigen. The import of U snRNAs that contain 5' m3GpppN caps and are complexed by Sm proteins (U1, U2, U4, and U5) is competed by coinjection with free m3GpppG, indicating a shared transport factor, but not by P(Lys)-BSA. The import of U6 snRNA, which lacks a m3GpppN cap and is not complexed by the Sm proteins, is competed by P(Lys)-BSA but not by free m3GpppG. Thus, by the criterion of kinetic competition, U6 snRNA import is identical to that of the karyophilic proteins P(Lys)-BSA and nucleoplasmin. Uniquely, the import of U3 snRNA, which contains a m3GpppN cap but does not bind Sm proteins is not competed by either free m3GpppG or P(Lys)-BSA. Thus, U3 snRNA appears to be imported by a novel third kinetic pathway.

Amino Acid Sequence↗
PubMed1991

[Anemia in children: hemoglobin changes in mild, acute infections].

Anemia is commonly discovered in children when a complete blood count is routinely performed during acute and febrile illnesses. In this study-recovery of hemoglobin levels in children after acute infections was evaluated. Hemoglobin levels were measured in capillary blood of 70 patients who visited a community primary pediatric clinic with an acute infectious illness (37 boys, 33 girls; mean age 22 months, mode 18; 58 had fever of 38 degrees or higher). The most frequent diagnoses were upper respiratory tract infection, acute otitis media and pharyngitis. Follow-up hemoglobin measurements were performed after at least 3 days without fever and when the children were considered well by their parents. The average time between the 2 measurements was 12 +/- 9 days.

Acute Disease↗
PubMed1991

Pathways for the nuclear transport of proteins and RNAs.

The nuclear pore complex catalyses the import and export of both proteins and RNAs. The molecular mechanisms of RNA and protein translocation through the nuclear pore are likely to be similar; however, their signals and targeting apparatus may differ. Recent insights into RNA transport have come from studies of kinetic control mechanisms and the preconditions for translocation that include processing, RNP assembly, and a targeting function for 5' caps.

Journal Article↗
PubMed1990

[Intracranial hemorrhage complicating acute disseminated staphylococcal disease in a child].

Acute disseminated staphylococcal disease may develop in previously healthy children below the age of 15 years. It progresses rapidly and may cause death in a significant number. The diagnostic criteria are infection in 2 or more anatomical sites and isolation of a coagulase-positive Staphylococcus aureus from the blood or from a site of infection. We present an 11.5-year-old boy with disseminated staphylococcal disease with evidence of cellulitis, osteomyelitis and endocarditis. He developed intracranial hemorrhage as a complication and survived, but with mild residual hemiparesis. Nervous system involvement, such as meningitis and brain abscess, have been described in this particularly severe disease. This is the only known report of intracranial hemorrhage as a complication of the disease.

Acute Disease↗
PubMed1990

Outer ear canal shape and its relation to the effectiveness of sound attenuating earplugs.

This investigation was undertaken to explore the relationship between the level of sound attenuation achieved by the wearing of hearing protectors, and the shape of the external ear canal. Bilateral molds of the outer portion of the external ear canal were made in 93 males and females with normal hearing, who had participated in a previous study on the effect of gender on sound attenuation, measured for a variety of insert type devices. The ear canal molds were analyzed in terms of tortuosity, caliber, and degree of funneling. The results showed that individuals with straight canals achieved significantly higher attenuation scores than those with twisted canals. With regard to caliber, the more important of the two parameters reviewed was the cross-sectional area of the canal measured at the cartilaginous-bony junction (IA). The relationship between IA and attenuation depended on both gender and the type of earplug tested. Funneling, measured by the ratio of concheomeatal and cartilaginous-bony cross-sectional areas, had the opposite effect of that for IA. These findings underscore the need for more controlled prescription and fitting procedures for the insert type of hearing protectors commonly used in the industrial setting.

Ear Canal↗
PubMed1987

Asymmetric affinity of Na+-H+ antiporter for Na+ at the cytoplasmic versus external transport site.

The affinity for Na+ of the cytoplasmic vs. external transport site of the amiloride-sensitive Na+-H+ antiporter was studied in confluent cultures of MDCK cells. Na+-H+ antiport activity was fluorometrically determined by monitoring changes in intracellular pH (pHi) using the pH-sensitive fluorescent probe, BCECF. Na+-dependent H+ fluxes were studied both in the functionally operative (H+ efflux/Na+ influx) and reverse (H+ influx/Na+ efflux) mode of antiport activity, under pH equilibrium, but Na+-gradient conditions. Thus the driving force for antiport activity was solely dependent on the transmembrane Na+ gradient. Independent experiments established that pHi and intracellular Na+ [Na+i] had been set at the desired values before the initiation of a particular experiment. Under conditions of pHi = pHo = 7.0, [Na+i] = 0 mM and varying extracellular Na+ concentration [Na+o], the apparent affinity for Na+ (KtNa) for the external transport site was 24 +/- 3 mM. When antiport activity was measured in the reverse mode of operation, but under identical pH conditions, KtNa at the internal site was 7 +/- 1 mM. When ambient pH was elevated to 7.5, KtNa at the internal site was 14 +/- 1 mM. Maximum H+ flux (JmaxH+) for the antiporter under all three conditions was not significantly different. In summary, the Na+-H+ antiporter displays asymmetric affinity for Na+ at the internal vs. external transport site. Under pH equilibrium conditions, the affinity of the Na+-H+ antiporter for Na+ is three- to four-fold greater at the internal vs. external locus, and the affinity for Na+ at the internal site is enhanced by lower pHi. The close similarity between values for KtNa (inside) and reported values for intracellular Na+ concentration suggests that regulation of the Na+-H+ antiporter may be affected by changes in intracellular Na+ concentration.

Animals↗
PubMed1987

Relationship between plasma renin activity and distal nephron sodium delivery and reabsorption in man.

The relationship between plasma renin activity and distal tubular sodium delivery and reabsorption was examined in man. Distal sodium delivery and reabsorption were measured during hypotonic volume expansion by the free water clearance method, or during hydropenia or isotonic volume expansion by the lithium clearance method. The maximal water diuresis method and the lithium clearance method both showed a negative correlation between plasma renin activity and distal sodium delivery and reabsorption. Only with the lithium clearance method, however, was it possible to measure plasma renin activity, distal sodium delivery and reabsorption in hydropenia without disturbances of water and electrolyte balance and plasma renin activity level. In hydropenia the plasma renin activity was higher and the fractional distal sodium delivery and reabsorption lower than during volume expansion. Our results support the idea that sodium chloride reabsorption at the macula densa region is negatively correlated to the plasma renin activity in man.

Absorption↗
PubMed1986

Characteristics of the Na+-H+ antiporter in the intact renal proximal tubular cell.

The characteristics of the proximal tubular Na+-H+ antiporter were determined in isolated proximal tubular cells to ascertain whether the features of this transport system in intact cells are comparable with those previously described for isolated brush-border membrane vesicles. A method is described for the rapid isolation of a purified preparation of cells that demonstrate morphological and functional characteristics of the renal proximal tubule. The cells maintain their polarity while in suspension, and adenylate cyclase activity is enhanced by parathyroid hormone but not by arginine vasopressin. The cells display gluconeogenic function and Na+-dependent alpha-methyl-D-glucose and organic phosphate cotransport, processes that confirm their proximal tubule origin. O2 consumption rates and cytosolic adenosine triphosphate levels indicate functional integrity. Na+-H+ antiport activity was defined in these cells by measuring amiloride-sensitive Na+ uptake. At intracellular pH = 6.4 vs. extracellular pH = 7.4, KtNa was 10.1 +/- 2.8 mM, and maximal sodium flux was 0.89 +/- 0.13 nmol X 10(6) cells-1 X K0.5 for amiloride and ethyl-isopropyl amiloride, measured at an external Na+ concentration of 1 mM, was observed at 2.5 X 10(-5) M and 2.9 X 10(-6) M, respectively. The external and internal loci of the exchanger displayed asymmetric affinity for the hydrogen ion: the apparent pK for the external site was 7.20-7.26 vs. less than 6.5 for the internal site. The internal site demonstrated features of positive cooperativity. In summary, the Na+-H+ antiporter present in the luminal membrane of the renal proximal tubule has been characterized in the intact cell and displays functional and kinetic parameters closely resembling those described in isolated brush-border membrane vesicles.

Adenylyl Cyclases↗
PubMed1985

Anorexia nervosa, laxative abuse, hypopotassemia and distal renal tubular acidosis.

A case of anorexia nervosa in a 28-year-old woman with laxative abuse, hypopotassemia and severe metabolic acidosis, is described. The diagnosis of classical renal tubular acidosis, Type I, was confirmed by our inability to decrease urinary pH beyond 5.5 and to increase ammonia excretion during an ammonium chloride loading test. A bicarbonate loading test and normal plasma aldosterone with high renin activity excluded proximal renal tubular acidosis, hyporeninemic-hypoaldosteronemic renal tubular acidosis and Bartter's syndrome. The inability to increase ammonium excretion during severe metabolic acidosis following ammonium chloride loading did not favor the possibility of a transient physiological adaptation of ammoniagenesis at the tubular cell level, related to potassium depletion. Although mental disorder, laxative abuse, abstinence from food intake and severe potassium depletion intermingled in a vicious cycle, we assume that one of the following possibilities may explain the clinical presentation in our patient: either two separated and unrelated disorders, or laxative abuse as the cause of renal tubular acidification impairment.

Acidosis, Renal Tubular↗
PubMed1984

Attenuation of injury due to unilateral renal ischemia: delayed effects of contralateral nephrectomy.

The functional abnormalities associated with unilateral postischemic acute renal failure in the rat, as produced by 60 min of complete renal artery occlusion, are influenced by the presence or absence of the contralateral kidney. When the contralateral kidney is removed prior to the ischemia, reflow of blood to the postischemic kidney is more complete. To determine whether this maneuver influenced the ultimate severity of the injury and, if so, to investigate the mechanism by which this occurred, studies were performed conjointly at Tel-Hashomer, Israel, and Chapel Hill, N.C., in uninephrectomized (UNx) and sham-operated (Sh) rats. At Tel-Hashomer, V from UNx rats was nearly double that found in Sh rats at 1 to 3, 3 to 5, and 24 hr after ischemia. By 24 hr, CCr was substantially greater in UNx rats and was similar to that from the nonischemic kidney of Sh rats. Differences in tubular function were also noted. In UNx rats, FENa at 24 hr was significantly less and TCH2O was significantly greater than the corresponding values determined in Sh rats. At Chapel Hill, by 24 hr, RBF and PGCe in UNx rats were significantly greater than the corresponding values in Sh rats, although both were less than values obtained in nonischemic kidneys. In UNx rats, RT and RPG were considerably less than the corresponding values in Sh rats and similar to the values obtained in nonischemic kidneys. Microscopic examination at 24 hr revealed widespread tubular epithelial cell necrosis in Sh rats. In contrast, tubular epithelial cell structures were preserved in UNx rats. These data indicate that substantive differences exist in the response to temporary unilateral renal ischemia, which depend in part on the absence of the contralateral kidney and which result in less severe reduction in RBF and CCr and the preservation of tubular epithelial structure and function.

Acute Kidney Injury↗
PubMed1984

Calcium-entry blockade and pressor effect of angiotensin II in normal and nephrectomized rats.

The pressor effect of intravascular boli of 1.5 micrograms/kg angiotensin II was studied in untreated and in verapamil-pretreated intact rats and in rats 24 h after bilateral nephrectomy. An initial i.v. dose of 250 micrograms/kg verapamil was followed by a continuous infusion of 7 micrograms/min per kg. This resulted, within 2 min, in an average decrease in mean arterial pressure of 19 +/- 3 (SE) mm Hg and 18 +/- 3 (SE) mm Hg in intact and bilaterally nephrectomized rats, respectively. This continuous dose of verapamil did not significantly prevent the pressor effect of angiotensin II. When the continuous infusion of verapamil was increased to 50 micrograms/min per kg, the rise in blood pressure following angiotensin II administration was significantly lower than in the untreated rats: 21 +/- 2 (SE) mm Hg in intact rats, compared with 39 +/- 3 (SE) mm Hg (P less than 0.001) in the untreated animals and 31 +/- 3 (SE) mm Hg in rats in the renoprival state, compared with 47 +/- 6 (SE) mm Hg (P less than 0.01) in the corresponding untreated group. The present study suggests that verapamil can be used as a calcium blocker to reduce blood pressure associated with, or caused by, an increased renin-angiotensin system activity.

Angiotensin II↗