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Biomedical subjects

S Stone

Publications and source records attributed to S Stone.

At least 109 records · Page 6Linked to original sources
PubMed1998

A survey of patient education postdischarge.

Through a telephone survey, the Discharge Call Service (DCS) was instituted with 206 patients discharged from two medical-surgical nursing units. The purposes of the survey were to (1) improve patient outcomes by assessing patient perceptions of their recuperation progress after discharge, (2) assess the patient's post discharge educational needs, (3) provide additional information concerning diagnosis, treatment, or medications requested by the patient, and (4) direct patients to the appropriate medical center or community resource as needed for further assistance or education. In general, patients believed their medical status was progressing as expected; nevertheless almost half of the patients surveyed needed additional information or specific directions concerning their self-care. Findings suggest the DCS is an effective strategy to enhance the patient's ability for self-care after discharge. The DCS is also an easily implemented and cost-effective enhancement of hospital patient education and health promotion activities.

Cross-Sectional Studies↗
PubMed1998

Increased expression of tumor necrosis factor-alpha and decreased expression of thyroglobulin and thyroid peroxidase mRNA levels in the thyroids of iodide-treated BB/Wor rats.

Several lines of evidence suggest that tumor necrosis factor-alpha (TNFalpha) may contribute to the pathogenesis of autoimmune thyroid disease. It is not known, however, whether increased thyroidal TNFalpha levels are associated with changes in thyroid function. The purpose of the present study was to utilize in situ hybridization histochemistry and immunohistochemistry to determine if the expression of TNF-alpha in the thyroid is associated with a decrease in thyroglobulin (Tg) and thyroid peroxidase (TPO) mRNA levels. Lymphocytic thyroiditis was induced in BB/Wor rats by iodide administration, and thyroidal Tg and TPO mRNA levels were assessed by Northern blot analysis and in situ hybridization, and TNFalpha expression by Northern blot analysis and immunohistochemistry. Thyroids were obtained before and 1 and 2 months after iodide administration. Hematoxylin and eosin staining revealed that there was a progressive increase in mononuclear cells in the thyroids of BB/Wor rats ingesting iodide for 1 and 2 months. Northern blot analysis revealed that during the same time course there was a progressive increase in TNFalpha mRNA levels and a progressive decrease in Tg and TPO mRNA levels in the thyroids. In situ hybridization histochemistry was performed to determine if the decrease in Tg and TPO mRNA levels was associated with thyroid follicular cells in contact with infiltrating mononuclear cells. In rats treated with iodide for 1 month, there was a modest decrease in Tg and TPO mRNA levels in follicular cells in contact with infiltrating mononuclear cells. After 2 months of iodide treatment there was clearly a localized decrease in Tg and TPO mRNA levels in follicular cells in contact with infiltrating mononuclear cells. Immunohistochemical analysis did not detect TNFalpha in the thyroids from control rats or from rats treated with iodide for 1 month. In contrast, after 2 months of treatment, TNFalpha was easily detected in infiltrating mononuclear cells and in some thyroid follicular cells. Together, these results suggest that the suppression of Tg and TPO mRNA levels was associated with the expression of TNFalpha and thus are in agreement with in vitro studies demonstrating that TNFalpha inhibits thyroid cell function.

Animals↗
PubMed1997

Pulmonary autograft procedure for aortic valve disease: long-term results of the pioneer series.

BACKGROUND: Pulmonary autograft replacement of the diseased aortic valve has not been widely practiced due to concerns regarding late autograft competence and the consequences of creating pulmonary valve disease. To investigate this, the fate of the pioneering series of patients has been determined. METHODS AND RESULTS: The 131 hospital survivors of the pulmonary autograft operation at the National Heart Hospital from 1967 to 1984 were identified and their outcomes determined to 1994. Age at operation was 11 to 52 years, and 109 patients were male. Autograft implantation was orthotopic subcoronary (107), free-standing root (20), or Dacron mounted (2). In 113 patients, homografts replaced the native pulmonary valve. Ten and 20 years after operation, survival was 85% and 61%, freedom from autograft replacement was 88% and 75%, and freedom from replacement of pulmonary position homografts was 89% and 80%, respectively. Causes of deaths (53) included chronic heart failure (13), complications of reoperation (12), and endocarditis (7). Autograft regurgitation, the most common indication for reoperation, appeared primarily technical in nature, usually due to cusp prolapse. Degeneration was found in only 3 of 30 explanted autografts, and the young patients showed no increase in late valve failure. Homografts outperformed other valve replacements in the pulmonary position, but patients with orthotopic subcoronary and root autografts survived similarly. CONCLUSIONS: The pulmonary autograft offers low rates of degeneration, endocarditis, and thromboembolism for a period lasting >20 years, particularly in the young, with reoperation mainly required for malpositioning of the autograft cusps. The capacity of the autograft to maintain viability with minimal degeneration is not matched by any other biological valve replacement.

Adolescent↗
PubMed1997

Cardiac surgery for grown-up congenital heart patients: survey of 307 consecutive operations from 1991 to 1994.

The cardiac surgery performed from 1991 to 1994 in a unit dedicated specifically for grown-up congenital heart (GUCH) patients was reviewed to determine the frequency of various procedures, incidence of first and reoperations, early mortality, and its determinants. The 295 patients, aged 16 to 77 years (31 +/- 13), had 307 operations. First operations (n = 128, 42%) were most commonly for closure of atrial septal defect (n = 40), aortic valve replacement (n = 31) or repair of aortic coarctation (n = 14). Reoperations were more frequent (n = 179, 58%) and divided among first corrective repair (n = 49), reoperation after corrective repair (n = 115), and further palliation (n = 15). First corrective surgery was mainly for aortic valve disease (n = 17), Fallot (n = 7), and lesions needing a Fontan procedure (n = 5). Reoperations after corrective repair were needed for aortic valve disease (n = 43), right-sided conduit (n = 30), or recoarctation (n = 11). Early mortality was influenced by presence of central cyanosis (9 of 49, 18% in cyanotic patients; 12 of 258, 5% in acyanotic; p <0.001), increased number of previous operations (0 = 4%, 1 = 7%, 2 = 11%, >2 = 13%; p = 0.003), and increasing age of patients. Cyanotic patients had more serious postoperative complications: pleural and pericardial effusions, severe bleeding, renal insufficiency, and sepsis, and their hospital stay was longer compared with acyanotic patients (20 +/- 17 vs 11 +/- 8 days; p <0.001). In GUCH patients, reoperations cause the largest demand on cardiac surgical services. Increased survival of patients with complex cardiovascular malformations brings difficult challenges not only to cardiologists but also to cardiovascular surgeons. There is a need to provide continued highly specialized care. Resources, patients, and funding should be concentrated in a few designated centers.

Adolescent↗
PubMed1997

The synaptobrevin-related domains of Bos1p and Sec22p bind to the syntaxin-like region of Sed5p.

SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors) are cytoplasmically oriented membrane proteins that reside on vesicular carriers (v-SNARE) and target organelles (t-SNARE). The pairing of a stage-specific v-SNARE with its cognate t-SNARE may mediate the specificity of membrane traffic. In the yeast Saccharomyces cerevisiae transport between the endoplasmic reticulum and Golgi complex employs two v-SNAREs, Bos1p and Sec22p, each containing a domain that is related to the neuronal v-SNARE synaptobrevin. Sed5p, which is homologous to syntaxin, is the t-SNARE that functions at this stage of the secretory pathway. Here we report that regions of Bos1p and Sec22p, which are homologous to synaptobrevin, bind to the syntaxin-like domain of Sed5p. Furthermore, we demonstrate that efficient v-SNARE/t-SNARE interactions require the participation of both v-SNAREs, indicating that, unlike post-Golgi membrane traffic, the active form of the endoplasmic reticulum to Golgi v-SNARE is a heteromeric complex.

Binding Sites↗
PubMed1997

Bet1p activates the v-SNARE Bos1p.

Bet1p is a type II membrane protein that is required for vesicular transport between the endoplasmic reticulum and Golgi complex in the yeast Saccharomyces cerevisiae. A domain of Bet1p, that shows potential to be involved in a coiled-coil interaction, is homologous to a region of the neuronal protein SNAP-25. Here, we used in vitro binding studies to demonstrate that Bet1p plays a role in potentiating soluble NSF attachment protein receptor (SNARE) interactions. Mutational analysis points to the coiled-coil region as necessary for Bet1p function, and circular dichroism experiments support this theory. In vitro binding studies were also used to demonstrate that a direct interaction between Bet1p and Bos1p is required for the efficient interaction of the vesicle SNARE with its SNARE target. Genetic studies suggest that the interactions of Bet1p with Bos1p are regulated by the small GTP-binding protein Ypt1p.

Amino Acid Sequence↗
PubMed1997

Low concentrations of ethanol inhibits prolactin-induced mitogenesis and cytokine expression in cultured astrocytes.

Whereas the immunosuppressive effects of chronic alcohol use have been well documented, little is known about the effect of ethanol on the neuroimmune response. We previously demonstrated that PRL is a potent mitogen and induces the expression of several inflammatory cytokines, including tumor necrosis factor-alpha (TNF alpha) in cultured rat astrocytes. The aim of this study was to examine the effects of ethanol on PRL-induced mitogenesis and TNF alpha expression in cultured rat astrocytes. We found that low concentrations of ethanol blocked PRL-induced increases in [3H]thymidine incorporation and TNF alpha levels. In contrast, ethanol had no effect on platelet-derived growth factor- or fibroblast growth factor-induced increases in [3H]thymidine incorporation. Radioligand binding analysis revealed that ethanol did not effect PRL receptor binding. We also examined the effect of prenatal alcohol exposure (PAE) on PRL-induced mitogenesis and cytokine expression. PAE during the last 5 days of gestation blunted the PRL-induced increase in [3H]thymidine incorporation and TNF alpha levels in cells grown in the absence of ethanol in the culture medium. Addition of ethanol to primary PAE astrocyte cultures resulted in a modest increase in basal [3H]thymidine incorporation, but completely blocked the PRL-induced increase in [3H]thymidine incorporation and TNF alpha levels. In contrast, platelet-derived growth factor- and serum (10%)-induced increases in [3H]thymidine incorporation remained intact. Together, these data indicate that ethanol blocks PRL-induced mitogenesis and the expression of TNF alpha in cultured rat astrocytes and are consistent with the possible inhibition of the astrocytic response by ethanol in vivo.

Animals↗
PubMed1996

Reversible, p16-mediated cell cycle arrest as protection from chemotherapy.

A model system has been developed to explore the relationship between cell cycle arrest and chemotherapeutic toxicity. An isopropyl-1-thio-beta-D-galactopyranoside-inducible P16 construct was introduced stably into a melanoma cell line and used to promote G0-G1 arrest in the recipient cells. The state of arrest was reversible and did not compromise cell viability over a period of at least 7 days. Isopropyl-1-thio-beta-D-galactopyranoside-treated, arrested cells were significantly more resistant to the chemotherapeutic agents methotrexate (approximately 50 times), vinblastine (>100 times), and cisplatin (approximately 10 times) compared to controls. This strategy of protection from chemotherapy exploits one of the basic genotypic differences between normal cells and tumor cells: the integrity of genetic pathways that regulate growth.

Antineoplastic Agents↗
PubMed1996

Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence.

p16CDKN2 specifically binds to and inhibits the cyclin-dependent kinases CDK4 and CDK6, which function as regulators of cell cycle progression in G1 by contributing to the phosphorylation of the retinoblastoma protein (pRB). Human cell lines lacking functional pRB contain high levels of p16 RNA and protein, suggesting a negative feedback loop by which pRB might regulate p16 expression in late G1. By a combination of nuclear run-on assays and promoter analyses in human fibroblasts expressing a temperature-sensitive simian virus 40 T antigen, we show that p16 transcription is affected by the status of pRB and define a region in the p16 promoter that is required for this response. However, the effect is not sufficient to account for the differences in p16 RNA levels between pRB-positive and -negative cells. Moreover, p16 RNA is extremely stable, and the levels do not change appreciably during the cell cycle. Primary human fibroblasts express very low levels of p16, but the RNA and protein accumulate in late-passage, senescent cells. The apparent overexpression of p16 in pRB-negative cell lines is therefore caused by at least two factors: loss of repression by pRB and an increase in the number of population doublings.

Base Sequence↗
PubMed1996

Effects of ceramide and protein kinase C on the regulation of type I 5'-deiodinase in FRTL-5 rat thyroid cells.

Tumor necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine that is involved in the regulation of thyroid growth and differentiated functions. The cellular and molecular mechanisms involved in mediating the effects of TNF alpha on thyroid function, however, are unknown. In a number of cell types, TNF alpha receptor binding results in the activation of specific signal transduction cascades, including protein kinase C (PKC) and the hydrolysis of sphingomyelin to ceramide. In the present study, we examined the possible role of PKC and the hydrolysis of sphingomyelin to ceramide in the regulation of TSH-induced increases in 5'-deiodinase (5'D-I) activity and 5'D-I messenger RNA (mRNA) levels in FRTL-5 cells. Further, we have recently shown that TNF alpha and interferon-gamma (IFN gamma) act synergistically to block TSH-induced increases in type I 5'D-I activity and 5'D-I gene expression in FRTL-5 rat thyroid cells. Thus, we tested the hypothesis that the activation of one or both pathways is involved in synergistic effect of TNF alpha and IFN gamma on thyroid function. In TSH-stimulated FRTL-5 cells, the addition of 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of PKC, inhibited TSH-induced increases in 5'D-I activity and 5'D-I mRNA levels in a dose-dependent manner. Incubation of FRTL-5 cells with TPA and a minimal effective concentration of IFN gamma (12.5 U/ml) in combination, however, failed to result in a synergistic inhibition of the TSH-induced increase in 5'D-I activity or 5'D-I mRNA levels. Similarly, incubation of FRTL-5 cells with sphingomyelinase (SMase), which converts sphingomyelin to ceramide, inhibited TSH-induced increases in 5'D-I activity and 5'D-I mRNA levels in a dose-dependent manner. Coincubation of FRTL-5 cells with SMase and IFN gamma failed to show a synergistic inhibition of the TSH-induced increase in 5'D-I activity or 5'D-I mRNA levels. Further, incubation of FRTL-5 cells with TPA plus SMase in the presence of IFN gamma failed to result in the synergistic inhibition of TSH-induced increases in 5'D-I activity or 5'D-I mRNA levels. The effect of TPA and SMase on TSH-induced cAMP production was examined. Low concentrations of TPA, which inhibit TSH-induced 5'D-I activity, failed to inhibit TSH-induced cAMP production or the cAMP-induced increase in 5'D-I activity. In contrast, SMase inhibited TSH-induced cAMP production in a dose-dependent manner. In the presence of IFN gamma, however, activation of either or both pathways is not sufficient to result in a synergistic inhibition of 5'D-I activity or 5'D-I gene expression. Together, our results suggest that TNF alpha-induced activation of PKC and hydrolysis of sphingomyelin can inhibit thyroid cell function. The activation of additional signal transduction pathways, however, by TNF alpha is required for the synergistic inhibition of thyroid function by TNF alpha and IFN gamma.

Analysis of Variance↗
PubMed1996

Involvement of tyrosine phosphorylation in the regulation of 5'-deiodinases in FRTL-5 rat thyroid cells and rat astrocytes.

Recent studies suggest that protein tyrosine phosphorylation may play a role in the regulation of thyroid growth and function. In the present study, we used genistein, a specific inhibitor of tyrosine phosphorylation, to determine if tyrosine phosphorylation is involved in the regulation of type I 5'-deiodinase (5'D-I) expression in FRTL-5 cells and type II 5'-deiodinase (5'D-II) in rat astrocytes. Incubation of FRTL-5 cells with genistein (100 microM) for 3 days had no effect on cell viability as assessed by trypan blue exclusion. In TSH-deprived cells, incubation of FRTL-5 cells with genistein (100 microM) resulted in a modest, but not significant, decrease in 5'D-I activity. Incubation of FRTL-5 cells with TSH (100 microU/ml), Bu2cAMP (0.5 mM) or forskolin (1 microM) resulted in marked increases in 5'D-I activity. In the presence of genistein (100 microns), however, the TSH, Bu2cAMP and forskolin-induced increases in 5'D-I activity were completely inhibited. In Bu2cAMP-stimulated FRTL-5 cells, incubation with genistein (1, 10, and 100 microM) resulted in a dose-dependent decrease in 5'D-I activity, with 100 microns genistein completely blocking the Bu2cAMP-induced increase in 5'D-I activity. Similarly, we found that in FRTL-5 cells, genistein (100 microns) completely blocked the Bu2cAMP-induced increase in 5'D-I messenger RNA (mRNA) levels, DNA synthesis as assessed by [3H]thymidine incorporation, and the T3-induced increase in 5'D-I activity. To determine if addition of genistein to FRTL-5 cells resulted in a general inhibition of Bu2cAMP-induced responses, we examined its effect on the Bu2cAMP-induced increase in c-fos mRNA levels. Bu2cAMP-induced c-fos mRNA levels were not affected by the treatment of cells with genistein (100 microM). We then examined the effect of genistein on the Bu2cAMP and hydrocortisone-induced 5'D-II activity in cultured rat astrocytes. Genistein (100 microM) had no effect on cell viability as assessed by trypan blue exclusion. In serum deprived astrocytes, addition of Bu2cAMP (1 mM) and hydrocortisone (100 nM) resulted in a 110-fold increase in 5'D-II activity. Addition of genistein (100 microM) to stimulated astrocytes completely blocked the Bu2cAMP and hydrocortisone-induced increase in 5'D-II activity. The present data suggest that tyrosine phosphorylation-dephosphorylation may play an important role in the regulation of thyroid hormone deiodination and action in the thyroid and brain.

Animals↗
PubMed1995

Regulation of prolactin receptor expression by estradiol in the female rat brain.

Prolactin (PRL) receptors have been identified in many tissues, including the brain, but little is known about their distribution and regulation. In the female rat brain, ovariectomy significantly (p < 0.05) decreased PRL binding capacity, but not the affinity, in the hypothalamus and pons-medulla. Using reverse transcription and polymerase chain reaction (RT-PCR) amplification and Western blot analyses we found both the long and short forms of the PRL receptor mRNAs and proteins in the hypothalamus, pons-medulla and cortex in the female rat. Ovariectomy decreased the expression of short, but not the long form of the PRL receptor in the hypothalamus and pons-medulla, but not the cortex. Administration of estradiol (1.0 mg per 100 g b.w.) restored the PRL binding capacity, protein and mRNA levels of the short form of the receptor back to control levels. These results suggest that the expression and distribution of PRL receptors in the brain are differentially regulated in specific brain regions.

Animals↗
PubMed1995

Homozygous loss of the p15INK4B gene (and not the p16INK4 gene) during tumor progression in a sporadic melanoma patient.

Homozygous deletions of 9p21, including the cyclin-dependent kinase inhibitor genes p16INK4 and p15INK4B, have been reported frequently in melanoma (as well as other tumor) cell lines. Germline mutations within the p16INK4 gene have also been described in a proportion of familial melanoma kindreds, suggesting that p16INK4 is the 9p21 "melanoma" gene. We have previously concluded that deletion of this chromosomal region can occur early (before metastasis) and in vivo in sporadic melanoma due to the identification of identical hemizygous losses on 9p21 in six autologous melanoma cell lines established from an individual patient (DX). These related cell lines have now been used to evaluate the timing of deletion/mutation of the p16INK4 and p15INK4B genes during tumor progression in melanoma. Surprisingly, homozygous deletions of a < or = 200-kb region surrounding p15INK4B, but not p16INK4, were detected in all six cell lines. Furthermore, single strand conformation polymorphism and sequencing analysis of the remaining p16INK4 allele in each case revealed only one intragenic mutation (in DX-6), whereas Western analysis provided evidence that p16INK4 protein was expressed in all six instances. These findings, taken together with those generated on other unrelated melanoma tumors and cell lines, suggest that hemizygous loss (or haplo-insufficiency) of the p16INK4 gene may be enough to place a melanocyte on a tumor pathway, and/or that the p16INK4 gene is not the sole 9p21 locus targeted in sporadic melanoma.

Carrier Proteins↗
PubMed1995

Genomic structure, expression and mutational analysis of the P15 (MTS2) gene.

The P15 gene (MTS2) encodes a cyclin-dependent kinase (CDK) inhibitor with considerable sequence identity and biochemical similarity to the CDK inhibitor p16. It is closely linked to the P16 gene (MTS1) and is homozygously deleted in many tumor cell lines. These features suggest that p15 may be a tumor suppressor. We have determined the genomic structure of P15 and examined its pattern of mRNA expression. In addition, we have shown that ectopic expression of p15 inhibits growth of tumor-derived cell lines. We have also searched for P15 mutations in tumor cell lines and in 9p21-linked melanoma kindreds. Other than the previously described homozygous deletions, no mutations of P15 were found. Collectively, these observations suggest a role for p15 in growth regulation, but a limited role for p15 in tumor progression.

Base Sequence↗