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S Stone

Publications and source records attributed to S Stone.

At least 127 records · Page 7Linked to original sources
PubMed1995

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Journal Article↗
PubMed1995

Complex structure and regulation of the P16 (MTS1) locus.

The p16 gene (P16, MTS1, CDKN2) encodes a negative regulator of the cell cycle. Molecular genetic techniques have been used to explore the role of p16 in normal development and cancer. Two transcripts derived from the p16 gene with distinct protein coding potentials are described. The previously undescribed transcript form has the same exons 2 and 3 as the p16-encoding mRNA but contains a different exon 1. The human p16 transcripts are detected in various tissues, and the ratio of the transcripts is regulated in both a tissue-specific and cell cycle-specific manner. The P16-derived mRNAs are probably generated from separate promoters, and transcription from one of the promoters appears to be regulated, at least in part, by the retinoblastoma gene product.

Base Sequence↗
PubMed1995

Prolactin induced expression of glial fibrillary acidic protein and tumor necrosis factor-alpha at a wound site in the rat brain.

To determine if PRL stimulates astrocyte proliferation and cytokine expression in vivo, we examined the effect of PRL on the wound-induced increase in the expression of glial fibrillary acid protein (GFAP) and tumor necrosis factor-alpha (TNF-alpha) in the CNS. Low levels of GFAP detected by Western blot analysis were identified in the non-wounded controls. Five days after the infliction of the wound, the relative abundance of GFAP in the tissue surrounding the wound site was greater than those of intact controls. Injection of PRL into the wound site markedly increased GFAP expression in the hypothalamus. Western blot analysis failed to detect TNF-alpha in the hypothalamus of non-wounded animals. In contrast, TNF-alpha was easily detected in the hypothalamus of wounded rats, and was markedly increased in PRL injected animals. To confirm the PRL-induced increase in TNF-alpha levels, TNF-alpha levels in hypothalamic extracts were measured by bioassay. In non-wounded controls, low but detectable TNF-alpha levels were found in the hypothalamus by bioassay (0.13 +/- 0.02 ng/mg protein). Infliction of a hypothalamic wound markedly increased TNF-alpha levels to 1.4 +/- 0.3 ng/mg protein. Injection of PRL into the wound site resulted in a further increase in TNF-alpha levels to 11.4 +/- 2.6 ng/mg protein. Further, infliction of the hypothalamic wound increased hypothalamic PRL content and PRL mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Prolactin induced expression of interleukin-1 alpha, tumor necrosis factor-alpha, and transforming growth factor-alpha in cultured astrocytes.

Prolactin (PRL) is a potent mitogen in cultured astrocytes. Because one of the major effects of astrocyte proliferation is the expression of inflammatory cytokines, we examined the effect of PRL-induced mitogenesis on the expression of interleukin-1 (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-alpha (TGF-alpha) in cultured astrocytes. Astrocytes were stimulated with PRL or growth hormone (GH), and the expression of cytokines was determined by immunohistochemistry and Western blot analysis. Following incubation of astrocytes with 1 nM PRL for 6 h, strong positive staining of IL-1 alpha and TNF-alpha, but not TGF-alpha, was found. No detectable staining for the above cytokines was found in vehicle, or GH treated astrocytes. When astrocytes were incubated in the presence of 1 nM PRL for 18 h, strong positive staining for IL-1 alpha and TGF-alpha was found. Immunocytochemical analysis of the expression of TNF-alpha and IL-1 alpha in PRL stimulated astrocytes suggested that the expression of IL-1 alpha preceded the expression of TNF-alpha. To confirm this observation, Western blot analyses were performed on extracts from astrocytes incubated with 1 nM PRL in unstimulated astrocytes, IL-1 alpha levels were not detectable. In astrocytes stimulated with 1 nM PRL, expression of IL-1 alpha was clearly detected after 1 h of incubation, and IL-1 alpha levels continued to increase during the course of the experiment (6 h). In contrast, in astrocytes stimulated with 1 nM PRL, an increase in the expression of TNF-alpha was first apparent after 2 h of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Comparative analysis of Homo sapiens and Mus musculus cyclin-dependent kinase (CDK) inhibitor genes p16 (MTS1) and p15 (MTS2).

Cyclin-dependent kinase inhibitors are a growing family of molecules that regulate important transitions in the cell cycle. At least one of these molecules, p16, has been implicated in human tumorigenesis while its close homolog, p15, is induced by cell contact and transforming growth factor-beta (TGF-beta). To investigate the evolutionary and functional features of p15 and p16, we have isolated mouse (Mus musculus) homologs of each gene. Comparative analysis of these sequences provides evidence that the genes have similar functions in mouse and human. In addition, the comparison suggests that a gene conversion event is part of the evolution of the human p15 and p16 genes.

Amino Acid Sequence↗
PubMed1995

Monitoring the efficacy of hybrid selection during positional cloning: the search for BRCA1.

Positional cloning often requires isolation of candidate genes from a large, genetically defined region. Hybrid selection (direct cDNA selection, solution hybrid capture) is a rapid, simple procedure that has been used to identify expressed sequence tags (ESTs) from cloned genomic DNA. We used hybrid selection to screen a 600-kb region that includes the BRCA1 gene. From a set of 931 sequenced clones, we obtained 118 nonoverlapping candidate ESTs from ovary and lymphocyte cDNA. We analyzed the results of our hybrid selection experiments with particular attention to the overall completeness, efficiency, and background noise of the experiment. We introduce simple parameters that serve as measures of important aspects of the hybrid selection process in the context of positional cloning.

BRCA1 Protein↗
PubMed1995

BET3 encodes a novel hydrophilic protein that acts in conjunction with yeast SNAREs.

Here we report the identification of BET3, a new member of a group of interacting genes whose products have been implicated in the targeting and fusion of endoplasmic reticulum (ER) to Golgi transport vesicles with their acceptor compartment. A temperature-sensitive mutant in bet3-1 was isolated in a synthetic lethal screen designed to identify new genes whose products may interact with BET1, a type II integral membrane protein that is required for ER to Golgi transport. At 37 degrees C, bet3-1 fails to transport invertase, alpha-factor, and carboxypeptidase Y from the ER to the Golgi complex. As a consequence, this mutant accumulates dilated ER and small vesicles. The SNARE complex, a docking/fusion complex, fails to form in this mutant. Furthermore, BET3 encodes an essential 22-kDa hydrophilic protein that is conserved in evolution, which is not a component of this complex. These findings support the hypothesis that Bet3p may act before the assembly of the SNARE complex.

Amino Acid Sequence↗
PubMed1995

Corrected transposition of the great arteries without associated defects in adult patients: clinical profile and follow up.

OBJECTIVE: To assess the clinical course of adult patients with corrected transposition of the great arteries without associated anomalies. DESIGN: All patients with corrected transposition of the great arteries without associated anomalies were reviewed with complete clinical and echocardiographic assessment. The complications were evaluated in each decade. SETTING: Tertiary centre with a specific unit dealing with "grown-up" adolescent and adult congenital heart disease, designated as a quaternary centre and a general hospital with a referral centre for "grown-up" congenital heart disease. PATIENTS: 18 patients (nine male and nine female) aged 16-61 years followed for 1-30 years (mean 10 years). RESULTS: There were no deaths. Six patients had a worsening ability index during follow up. Complications were: (a) complete heart block in seven, three of whom required pacemaker insertion; (b) significant left atrioventricular valve regurgitation in 50%, appearing only in the third decade (12%), with increasing frequency thereafter. Infective endocarditis was responsible for increasing left atrioventricular valve regurgitation in only one patient; (c) supraventricular arrhythmia appeared in the fifth decade, and occurred in all patients over the age of 60 years. One patient aged 61 had recurrent sustained ventricular tachycardia; and (d) congestive heart failure developed only after 50 years in 66%. One patient had severe left atrioventricular valve regurgitation; the function of the systemic ventricle was only moderately reduced in the other three. Three of the nine women had seven uneventful pregnancies. CONCLUSIONS: Patients with corrected transposition of the great arteries without associated defects may remain undiagnosed until adult life. Symptoms occur rarely before the fourth and fifth decades, when rhythm disturbance, left atrioventricular valve regurgitation, and moderately impaired systemic ventricular function cause congestive cardiac failure. The role of pacemaker insertion or surgery for left atrioventricular valve regurgitation needs further assessment.

Adolescent↗
PubMed1994

Ypt1p implicated in v-SNARE activation.

Synaptobrevin-like membrane proteins that reside on transport vesicles, called the vesicle SNARE (v-SNARE), play a key role in ensuring that a vesicle targets and fuses with its correct acceptor compartment. Here we show that Bos1p, the v-SNARE of yeast endoplasmic reticulum-to-Golgi transport vesicles, pairs with another integral membrane protein of similar topology (Sec22p) on vesicles. This pairing, which appears to require functional Ypt1p (Rab in mammalian cells), may aid the activity of Bos1p on this compartment. These findings suggest that Rabs regulate the specificity of membrane fusion by selectively activating the v-SNARE on carrier vesicles. Because the v-SNARE resides on more than one membrane, such a regulated activation step may be necessary to prevent the premature fusion of donor and acceptor compartments.

Biological Transport↗