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Biomedical subjects

D J Goldstein

Publications and source records attributed to D J Goldstein.

At least 127 records · Page 7Linked to original sources
PubMed1992

Beneficial health effects of modest weight loss.

The medical effects of modest weight reduction (approximately 10% or less) in patients with obesity-associated medical complications were reviewed. The National Library of Medicine MEDLINE database and the Derwent RINGDOC database were searched to identify English language studies that examined the effects of weight loss in obese patients with serious medical complications commonly associated with obesity (non-insulin dependent diabetes mellitus (NIDDM or type II), hypertension, hyperlipidemia, hypercholesterolemia, and cardiovascular disease). Studies in which patients experienced approximately 10% or less weight reduction were selected for review. Studies indicated that, for obese patients with NIDDM, hypertension or hyperlipidemia, modest weight reduction appeared to improve glycemic control, reduce blood pressure, and reduce cholesterol levels, respectively. Modest weight reduction also appeared to increase longevity in obese individuals. In conclusion, a large proportion of obese individuals with NIDDM, hypertension, and hyperlipidemia experienced positive health benefits with modest weight loss. For patients who are unable to attain and maintain substantial weight reduction, modest weight loss should be recommended; even a small amount of weight loss appears to benefit a substantial subset of obese patients.

Cardiovascular Diseases↗
PubMed1991

Bovine papillomavirus E5 oncoprotein binds to the 16K component of vacuolar H(+)-ATPases.

The major transforming protein of bovine papillomavirus type 1, E5, is mainly associated with endomembranes, specifically binding to a cellular protein of relative molecular mass 16,000 (16K). At the same time as transformation, E5 causes the phosphorylation of tyrosine residues in epidermal and platelet-derived growth factor receptors. We show here that the 16K protein associated with E5 is the 16K component of vacuolar ATPases. This protein is known to be an integral membrane protein in endosomes, bovine chromaffin granules, synaptic vesicles, fungal and plant vacuoles and clathrin-coated vesicles, as well as a component of gap-junction-like membrane complexes. Because proton pumps are critical for the function of cellular compartments that process growth-factor receptors, the interaction of E5 with the 16K protein could explain the pleiomorphic features of cells transformed by E5.

Adenosine Triphosphatases↗
PubMed1991

A genomic sequence of the Schizosaccharomyces pombe 16 kDa vacuolar H(+)-ATPase.

We have isolated the gene encoding the 16 kDa vacuolar H(+)-ATPase from Schizosaccharomyces pombe. On the basis of RNA splicing signals and amino acid sequence homology with other 16 kDa H(+)-ATPases, the genomic DNA sequence indicated the 16 kDa protein is encoded by five exons. The C-terminal 50 amino acids has more than 90% homology with vacuolar H(+)-ATPases of mammalian cells.

Amino Acid Sequence↗
PubMed1991

Changes in cellular dry mass during macrophage development.

Measurements of dry mass were made on developing human macrophages in suspension culture using a scanning and integrating microinterferometer. The mean dry mass (+/- SEM) of day 0 monocytes of 19 healthy individuals was 53.6 +/- 2.4 pg. There was a significant increase in cellular dry mass over the period of culture, mean values at 2, 4 and 6 days being 61.1, 79.8 and 110.4 pg, respectively. A comparison of the results with those obtained previously by ultrastructural morphometry inferred that there is a disproportionate increase in the water content of macrophages during development. The technique may have potential for investigating changes in mononuclear phagocytes in clinical states.

Adult↗
PubMed1991

Opiate receptors: opioid agonist-antagonist effects.

Two concepts are especially important in understanding the action of agonist-antagonist opioid analgesics. First, knowing to which receptor classes an agonist-antagonist binds permits prediction of its pharmacodynamics. For instance, psychotomimetic effects occur with binding to specific opiate (kappa) and nonopiate (sigma) receptors. Second, to have limited agonist activity despite increasing dose ceiling effect, the antagonist effect usually is of the same receptor class as the agonist effect.

Humans↗
PubMed1990

The E5 oncoprotein of bovine papillomavirus binds to a 16 kd cellular protein.

The E5 oncoprotein of bovine papillomavirus type 1 is the smallest known viral transforming protein. It is a 44 amino acid polypeptide asymmetrically oriented in Golgi and plasma membranes which appears to modify (either directly or indirectly) the internalization and phosphorylation of at least two growth factor receptors: EGF and CSF-1. To identify cellular proteins associated with E5, we have constructed two E5 fusion proteins, each of which contains a well-characterized epitope at the E5 amino terminus. These E5-epitope fusion proteins are biologically active, localize normally to cellular membranes and form dimers. Both monoclonal and polyclonal antibodies against the inserted epitopes specifically co-precipitate E5 and an associated 16 kd cellular protein. A transformation-defective E5 mutant containing a substitution within the hydrophobic portion of E5 is defective in its ability to bind the 16 kd protein. These findings suggest a role for E5/16 kd binding in the process of cellular transformation.

Animals↗
PubMed1990

Interaction of angiotensin II with the cholinergic and noradrenergic systems in the rat pineal gland: regulation of indole metabolism.

The pineal gland, angiotensin, and noradrenergic and cholinergic systems are involved in the regulation of tissue indole metabolism. Angiotensin II increased noradrenaline release and the production of hydroxy- and methoxyindoles by pineal slices. Electrical field stimulation (EFS) of pineal slices released angiotensin II and reproduced many of the actions of exogenous angiotensin II on serotonin and melatonin biosynthesis and release. Both sarcosine-isoleucine-angiotensin II ([Sar, Ile]-ANG II) and atropine blocked, and nadolol increased, the effect of EFS and exogenous angiotensin II on serotonin production. Nadolol blocked both the EFS-induced and the angiotensin II-induced production of melatonin. Atropine and [Sar, Ile]-ANG II did not modify melatonin biosynthesis in electrically stimulated slices, but the muscarinic receptor antagonist increased the stimulatory effect of angiotensin II. These data showed that EFS released angiotensin II and noradrenaline from pineal slices and that a close functional connection exists between the peptide and acetylcholine. The stimulation of serotonin biosynthesis and release by these two neurotransmitters was negatively regulated by noradrenaline acting through beta-adrenergic receptors.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1989

A herpes simplex virus ribonucleotide reductase deletion mutant is defective for productive acute and reactivatable latent infections of mice and for replication in mouse cells.

Herpes simplex virus encodes a ribonucleotide reductase that is not essential for virus growth in dividing cells at 37 degrees. This enzyme has been proposed as a target for antiviral drugs; its utility in this regard could depend upon its importance in vivo. To test the requirement of viral ribonucleotide reductase in a mammalian host, we tested a mutant virus, lacking most of the gene encoding the ribonucleotide reductase large subunit, in a mouse eye model of pathogenesis and latency where the wild-type virus establishes reactivatable latent infections in trigeminal ganglia following corneal inoculation. The deletion mutant was severely impaired in its ability to replicate acutely in the eye and in the trigeminal ganglion and failed to establish reactivatable latent infections. In contrast, a recombinant virus in which the deleted sequences were restored was competent for both acute and latent infections. The defects of the deletion mutant in the mouse may be related to its severely impaired growth at 38 degrees in mouse cells relative to its growth in Vero cells. These results indicate that ribonucleotide reductase is critical for productive acute and reactivatable latent infections in mice and replication in mouse cells at 38 degrees and suggest that caution be exercised in extrapolating from studies conducted in mice to human infections when judging the utility of this enzyme as a target for antiviral chemotherapy.

Acute Disease↗
PubMed1989

Herpes simplex virus ribonucleotide reductase mutants are hypersensitive to acyclovir.

Two mutants defective in herpes simplex virus-encoded ribonucleotide reductase activity exhibited the novel phenotype of hypersensitivity to acyclovir, aphidicolin, and to a lesser extent, phosphonoacetic acid. These results have implications for acyclovir resistance and the development of drugs that potentiate acyclovir action by inhibition of viral ribonucleotide reductase.

Acyclovir↗
PubMed1989

Concurrent validity of the Gardner Test of Visual-Motor Skills.

Scores on the Test of Visual-motor Skills, Developmental Test of Visual-motor Integration, and Bender-Gestalt test were compared for a sample of 44 elementary school children referred for evaluation of learning disorders. While the tests shared common variance, the mean standard score on the Test of Visual-motor Skills was significantly lower than the means of the other two tests, suggesting caution in the clinical use of the new scale.

Bender-Gestalt Test↗
PubMed1988

Overgrowth, congenital hypotonia, nystagmus, strabismus, and mental retardation: variant of dominantly inherited Sotos sequence?

We report on 2 patients with macrocephaly, strabismus, esotropia, nystagmus, hypotonia, developmental delay, excessive size, unusual facial appearance, and improvement with age. Many of these abnormalities are present in Sotos sequence. The mothers of both patients share some characteristics with their children. These patients may represent an autosomal dominant form of Sotos sequence.

Female↗
PubMed1988

Nager acrofacial dysostosis: evidence for apparent heterogeneity.

Nager acrofacial dysostosis is characterized by malar, mandibular, and maxillary hypoplasia, macrostomia, abnormal ears, and radial defects. The lower limbs are usually normal. Two patients were reported with many of these manifestations, in addition to severe facial clefts and limb deficiency. These more severely affected patients were thought to have a severe form of Nager acrofacial dysostosis or a new syndrome. We report on a patient with limb findings of intermediate severity. This patient also had hydrocephalus, micropolygyria, and tetralogy of Fallot. This may indicate apparent heterogeneity or a single condition with widely variable expression.

Craniofacial Dysostosis↗
PubMed1988

Factor(s) present in herpes simplex virus type 1-infected cells can compensate for the loss of the large subunit of the viral ribonucleotide reductase: characterization of an ICP6 deletion mutant.

Herpes simplex virus type 1 encodes a ribonucleotide reductase (RR) consisting of two subunits (140 and 38 kDa) whose genes map to coordinates 0.56 to 0.60 on the viral genome. We previously reported the isolation and characterization of a mutant with a lacZ insertion into the large subunit (ICP6) gene (Goldstein and Weller, 1988). Studies with this blue-plaque mutant, hrR3, showed that the viral RR activity is not essential in dividing cells in culture. This mutant, however, synthesizes the N-terminal one-third (434 amino acids) of ICP6 which may have an additional, required function. To test this possibility, a deletion of the ICP6 gene was created by introducing a deleted ICP6 gene into infectious hrR3 DNA and screening for white plaques from a background of blue plaques. Studies with this mutant, ICP6 delta, demonstrated that ICP6 is not required for virus growth and DNA synthesis in dividing cells in culture. However, we show that the ability of ICP6 delta to grow and induce viral DNA synthesis is dependent on the state of the infected cells; ICP6 delta is severely compromised in nondividing cells or in cells at 39.5 degrees. We propose that an alternate pathway(s) for obtaining deoxyribonucleotides is operating in infected cells and can compensate for defects in viral RR. In addition, our experiments suggest that these alternate sources are not available either in nondividing cells or in cells at 39.5 degrees.

Animals↗
PubMed1988

Expression and localization of myelin basic protein in oligodendrocytes and transfected fibroblasts.

Myelin basic protein (MBP) is a major structural component of myelin. It is expressed exclusively in myelinating glia (oligodendrocytes in the CNS and Schwann cells in the PNS) and is localized to the cytoplasmic surface of the plasma membrane and myelin membrane produced by these cells. The work described here concerns the mechanism of plasma membrane localization of MBP in myelinating glial cells and whether it involves differentiated functions specific to these cells or general functions of plasma membrane assembly common to all cells. To this end, the subcellular localization of endogenous MBP in mouse oligodendrocytes was compared with that of transiently expressed MBP in monkey fibroblasts (Cos-1 cells) transfected with an MBP expression vector containing cDNA for rat 14K MBP. The steady-state levels of MBP-specific RNA and of MBP polypeptide expressed in the transfected fibroblasts were comparable to the levels expressed in oligodendrocytes in primary culture. MBP localization was analyzed in whole cells by immunofluorescence and in specific intracellular compartments by subcellular fractionation. The results show that MBP expressed in wild-type oligodendrocytes is localized to the plasma membrane. In contrast, MBP expressed in transfected fibroblasts appears dispersed in the cytoplasm and is distributed uniformly among the various subcellular fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Herpes simplex virus type 1-induced ribonucleotide reductase activity is dispensable for virus growth and DNA synthesis: isolation and characterization of an ICP6 lacZ insertion mutant.

Herpes simplex virus (HSV) encodes a ribonucleotide reductase consisting of two subunits (140 and 38 kilodaltons) whose genes map to coordinates 0.56 to 0.60 on the viral genome. Host cell lines containing the HpaI F fragment which includes the reductase subunit genes of HSV type 1 strain KOS (coordinates 0.535 to 0.620) were generated. Transfection of these cells with a plasmid containing the immediate-early ICP0 gene resulted in the expression of ICP6; interestingly, ICP4 plasmids failed to induce expression, indicating an unusual pattern of ICP6 regulation. One such cell line (D14) was used to isolate a mutant with the structural gene of lacZ inserted into the ICP6 gene such that the lacZ gene is read in frame with the N-terminal region of ICP6. This mutant generated a protein containing 434 amino acids (38%) of the N terminus of ICP6 fused to beta-galactosidase under control of the endogenous ICP6 promoter. Screening for virus recombinants was greatly facilitated by staining virus plaques with 5-bromo-4-chloro-3-indoyl-beta-D-galactoside (X-gal). Enzyme assays of infected BHK cells indicated that the mutant is incapable of inducing viral ribonucleotide reductase activity. Surprisingly, although plaque size was greatly reduced, mutant virus yield was reduced only four- to fivefold compared with that of the wild type grown in exponentially growing Vero cells. Mutant virus plaque size, yields, and ability to synthesize viral DNA were more severely compromised in serum-starved cells as compared with the wild type grown under the same condition. Although our evidence suggests that the HSV type 1 ribonucleotide reductase is not required for virus growth and DNA replication in dividing cells, it may be required for growth in nondividing cells.

Cell Line↗
PubMed1988

An ICP6::lacZ insertional mutagen is used to demonstrate that the UL52 gene of herpes simplex virus type 1 is required for virus growth and DNA synthesis.

An insertional mutagen was developed which consists of the lacZ gene of Escherichia coli under the control of the regulatory elements of the large subunit of ribonucleotide reductase (ICP6). This ICP6::lacZ cassette was used to create a mutation in a gene designated UL52 (D. J. McGeoch, M. A. Dalrymple, A. Dolan, D. McNab, L. J. Perry, P. Taylor, and M. D. Challberg, J. Virol. 62:444-453, 1988), which is predicted to encode a 114,000-molecular-weight protein. To isolate and propagate this mutant, we generated a cell line, BL-1, by cotransfection of Vero cells with pSV2neo and a plasmid containing the herpes simplex virus type 1 KOS strain BamHI L fragment (coordinates 0.708 to 0.745). An ICP6::lacZ insertion mutant, hr114, was capable of growing in BL-1 cells but not in normal Vero cells. In addition, hr114 was defective in the synthesis of viral DNA and late proteins; however, this mutant appeared to exhibit normal early gene expression. Thus, the results presented in this report show that the UL52 gene product is required for viral DNA synthesis. Furthermore, our studies indicate that the ICP6::lacZ cassette will provide a useful tool for obtaining mutants of other herpes simplex virus genes.

Animals↗