PubMed Health⌕ Search

Biomedical subjects

S S Solomon

Publications and source records attributed to S S Solomon.

At least 19 recordsLinked to original sources
PubMed2006

Trends in HIV-related morbidity among patients admitted to a South Indian tertiary hospital between 1997 and 2003.

This paper describes trends in HIV-related morbidity among people living with HIV/AIDS (PLWHA) admitted to a tertiary hospital in Chennai, South India, between 1997 and 2003. Patients comprised HIV-infected men, women and children who had been admitted at least once to YR Gaitonde Centre for AIDS Research and Education (YRGCARE). A non-parametric trends analysis was conducted to observe trends in clinical and demographic parameters and diagnoses at admission over the seven-year period. Among clinical and demographic parameters, we identified a significantly increasing time trend in the use of antiretroviral therapy (p<0.001) and a significant decrease in the mean hemoglobin level (p=0.01). Among diagnoses at admission, we identified a decreasing time trend for admissions due to pulmonary tuberculosis (p<0.001) and increasing trends for admissions due to extra pulmonary tuberculosis (p<0.01), toxoplasmosis (p<0.01), Pneumocystis carinii pneumonia (p=0.02) and anemia (p<0.001). The results indicate a changing pattern among the clinical conditions requiring admission. With increasing proportions of patients initiating highly active antiretroviral therapy (HAART), it is probable that adverse events due to HAART will account for larger proportions of admissions in the years to come, as is being seen in the industrialized countries.

Adult↗
PubMed2006

AIDS in India.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed2004

Dried blood spots are an acceptable and useful HIV surveillance tool in a remote developing world setting.

Enzyme-linked immunosorbent assay and Western blot analysis of dried blood spots (DBS) on filter paper have been shown to be as sensitive and specific as analysis of serum, and therefore may be a cost-effective and culturally appropriate HIV seroprevalence tool in remote areas. This study examines the acceptability of DBS in a tropical, rural population from an outpatient clinic in Andhra Pradesh, India, where participation was offered to every fifth patient seeking general medical care between March and April 2001. All 1413 patients approached for the study agreed to participate and provide a DBS for examination. The overall HIV seroprevalence in this sample was 2.8%. Of the participants, 51.7% were male, 93.2% were between the ages of 18 and 40, 85.3% were married, 29.7% were employed, 47.6% had no education and 73.1% resided in a rural setting. In the univariate analysis, history of genital warts (P = 0.01), sexually transmitted disease (P = 0.001), premarital sexual intercourse (P = 0.002), sexual contact with a commercial sex worker (P = 0.003), being employed (P = 0.011) and having more than 10 injections for medical purposes (P = 0.006) all correlated with being HIV-infected. Given the uniform willingness of these clinic attendees to be tested, we conclude that DBS is a useful, cost-effective tool in HIV serosurveillance in a rural, tropical setting.

Adolescent↗
PubMed2001

Mechanisms involved in tumor necrosis factor-alpha induction of insulin resistance and its reversal by thiazolidinedione(s).

Insulin resistance (IR) remains one of the major pathogenic mechanisms for non-insulin-dependent type 2 diabetes mellitus. We have previously modelled IR in H-411E liver cells in culture. In past experiments, we used both labeled glucose uptake, lipogenesis, and stimulation of calmodulin gene expression to quantify the ability of the antidiabetic drugs (pioglitazone and metformin) to reverse tumor necrosis factor-alpha (TNF-alpha)-induced IR in these insulin-treated cells. In these current experiments, H-411E liver cells were rendered IR by a combination of TNF-alpha and insulin. In other experiments, the ability of C2 ceramide (Cer) to inhibit insulin action and induce IR was assessed as well as the phospholipase C inhibitor D609 to reverse IR induced by these TNF-alpha-like agents. C2 Cer, like TNF-alpha, inhibited insulin action. D609 reversed TNF-alpha induced--and to a lesser extent, C2 Cer-induced--IR. At selected times, the cells were also treated with troglitazone (TRG) in 2 groups: (1) 1-time exposure and (2) chronic exposure followed by acute exposure. TRG concentrations ranged from 0.015 to 15.0 micromol/L. Our data demonstrate a powerful effect of TRG in reducing IR and restoring insulin sensitivity in TNF-alpha-treated H-411E cells. Furthermore, pretreatment with TRG, reflecting chronic exposure, as in human clinical use, was more potent than 1-time acute exposure. These data support the efficacy of using thiazolidinediones (TRG) in human type 2 diabetes, and support the use of this cell culture model to further study the effects of thiazolidinediones on TNF-alpha-induced insulin resistance.

Animals↗
PubMed2001

Insulin deprivation leads to deficiency of Sp1 transcription factor in H-411E hepatoma cells and in streptozotocin-induced diabetic ketoacidosis in the rat.

Members of the family of Sp transcription factors include Sp1, Sp3, and Sp4 and are important regulators of eukaryotic gene expression. We previously reported that Sp1 mediated stimulation of rat calmodulin I gene expression in response to insulin. To test whether other members of the Sp family are direct targets of insulin action, we compared the levels of Sp1 and Sp3 proteins from nuclear extracts obtained from both insulin-treated and untreated rat hepatoma (H-411E) cells. We demonstrated by Western blot analysis that levels of Sp1 and Sp3 proteins were increased more than 2-fold in the insulin-treated group. Additionally, the up-regulation of both Sp1 and Sp3 transcription factors by insulin was antagonized by tumor necrosis factor-alpha, a known inhibitor of insulin action. Immunohistochemical analysis demonstrated that H-411E cells treated with insulin (10,000 microU/ml) had a marked increase in demonstrable Sp1 in the nucleus compared with cells incubated in insulin-free medium. We extended these in vitro observations to in vivo studies in the streptozotocin-diabetic rat model. We demonstrated in rat liver tissue by both Western blot and immunohistochemical staining with anti-Sp1 antibody that 1) livers of fully diabetic streptozotocin rats have low levels of Sp1 transcription factor; and 2) insulin treatment of the diabetic rat rapidly reversed this process by markedly stimulating accumulation of Sp1 in rat liver. Studies of the signal transduction mechanisms involved in insulin's effect on Sp1 demonstrate a facilitating role for phosphoinositol 3-kinase and an inhibitory role for cyclic nucleotides. In summary, insulin stimulates Sp1 protein, a transcription factor that is shown to regulate calmodulin gene expression and most likely other, as yet untested, genes.

Animals↗
PubMed2000

Members of the Sp transcription factor family regulate rat calmodulin gene expression.

We have previously demonstrated that insulin positively regulates transcription of the rat calmodulin (CaM) I gene and that both basal and insulin stimulation of this gene are critically dependent on Sp1. Furthermore, a 392 bp CaM promoter was stimulated by insulin equal to the full promoter but lost activity with deletion of any of the three Sp1 sites (Solomon SS, Palazzolo MR, Takahashi T, Raghow R. Endocrinology 1997;138:5052-5054). Herein we document that Sp1 preferentially binds to the upstream sites Sp1(2) and Sp1(3) but not Sp1(1). Furthermore, gel-mobility super-shift assays demonstrate that both Sp1 and Sp3 protein are found in these complexes. When pPac-Spl, pPac-Sp3, pPac-USp3, and pPac-Sp4 were cotransfected with rCaM 1-392 promoter into Drosophila SL2 cells and challenged with 10,000 microU/mL insulin, we discovered that (1) Sp1 enhanced both basal and insulin-stimulated CaM I gene expression; (2) USp3, a "long" form of the Sp3 molecule, had a stimulatory effect on CaM I gene expression; (3) Sp1 or USp3 is involved in mediating insulin-stimulation of the CaM I gene in SL2 cells; and (4) Sp3, a "short" form of the Sp3 molecule, and Sp4 inhibited Spl-stimulated and insulin-stimulated Sp1-mediated CaM I gene expression. Together these data corroborate and extend our previous observations on Sp1 and elucidate that other members of the Sp family of transcription factors may also be involved in regulating the activity of the CaM promoter.

Animals↗
PubMed1997

Identification of specific sites in the TNF-alpha molecule promoting insulin resistance in H-411E cells.

Data from a number of laboratories support a potential role for tumor necrosis factor-alpha (TNF-alpha) in the loss of insulin sensitivity and the pathogenesis of insulin resistance (IR) in diabetic animal models and human patients. We designed experiments to establish a dose-response relationship for TNF-alpha and IR in H-411E cells in culture. IR was measured by inhibition of the ability of graded amounts of insulin to stimulate expression of calmodulin (CaM) mRNA in these cells. This was assessed by autoradiographs of Northern blot(s) of CaM mRNA probed with labeled oligonucleotide cDNA for rat CaM. We found that TNF-alpha at 0.1, 1.0, and 10.0 ng/ml opposed 10,000 microU/ml insulin (i.e., %IR = 20%, 67%, and 88%, respectively). At 1.0 ng/ml TNF-alpha, insulin at the concentration of 1000 microU/ml (0.006 micromol/L) stimulated CaM mRNA at a 41% level and at 10,000 microU/ml (0.06 micromol/L) at a 63% level. Furthermore, oligopeptide TNF-alpha homologs (at 1000 x the molar concentration of TNF-alpha) TNF-alpha 69-100 and TNF-alpha 133-157 conferred 66% and 101% IR, respectively, while all other peptide fragments of TNF-alpha were essentially without effect. Studies done with both monoclonal and polyclonal antibodies to the TNF-alpha receptor demonstrated blocking activity by polyclonal but not by monoclonal anti TNF-alpha receptor antibody. This supports the concept that the activity of the peptide fragments occurs through the TNF-alpha receptor and not through nonspecific translocation across the plasma membrane. These data suggest that the epitopes on TNF-alpha that mediate IR reside in two regions of the molecule spanning amino acid residues 69-100 and 133-157.

Amino Acid Sequence↗
PubMed1997

Pioglitazone and metformin reverse insulin resistance induced by tumor necrosis factor-alpha in liver cells.

Tumor necrosis factor-alpha (TNF-alpha) has recently been implicated as a cause of insulin resistance (IR) in obesity and non-insulin dependent diabetes mellitus (NIDDM). To examine mechanisms involved, we induced IR induced IR in H-411 E cells with graded doses of TNF-alpha and measured the ability of insulin (INS) to stimulate both calmodulin (CaM) mRNA and glucose utilization. With TNF-alpha concentration at 1 ng/ml and 10(4) muU/ml INS, metformin 10 microM and pioglitazone 1.5 microM, reversed the IR induced by TNF-alpha restoring biologic response to 100% of INS effect alone. Furthermore, comparable results were obtained with glucose utilization/oxidation experiments in the H-411 E cells using glucose U-14C, trapping 14CO2 release in a hyamine filter and extracting 14C labelled lipids with Dole's reagent. In condusion, these data add scientific support for the use of both metformin and pioglitazone in treatment of IR in NIDDM patients and support a rationale for use of use of these drugs alone, and in conjuction with oral agents and/or INS treatment.

Animals↗
PubMed1997

Transcription factor Sp1 is necessary for basal calmodulin gene transcription and for its selective stimulation by insulin.

Insulin positively regulates transcription of rat calmodulin (CaM) I gene and activates the low Km cyclic AMP (cAMP) phosphodiesterase (PDE). To elucidate the mechanism of transcriptional regulation, rat hepatoma (H-411E) cells were transfected with DNA constructs containing the putative CaM promoters coupled to a luciferase reporter and challenged with insulin. Activation of the full length 1835 bp rat CaM I promoter containing all three Sp1 sites or truncated promoters with combinations of one to three of the Sp1 sites was studied in Sp1 deficient Drosophilia SL2 cells and in SL2 cells co-transfected with an Sp1 expression vector and re-challenged with insulin. Our results demonstrate that Sp1 is obligatory for basal activation of the CaM promoter. The maximal insulin stimulation of CaM promoter is elicited only if it contains at least two Sp1 sites.

Animals↗
PubMed1997

Insulin stimulates rat calmodulin I gene transcription through activation of Sp1.

We have shown previously that insulin positively regulates transcription of the rat calmodulin (CaM) I gene. This activation occurs concomitantly with the activation of the low-Km adenosine 3':5'-cyclic phosphate phosphodiesterase (PDE), which appears to be coregulated with CaM. Rat hepatoma H-411E cells were transfected with plasmids containing various lengths of the putative CaM promoter coupled to a luciferease reporter and were challenged with insulin. We demonstrate that insulin-stimulated transcription of CaM I gene is mediated by a 392-bp 5'-flanking region of the CaM I gene, encompassing 185 bp downstream and 207 bp upstream of the start site of transcription. The CaM I promoter contains three potential Sp1 sites, located at -114 through -109 [(3), +], -77 through -72 [(2), -] and at +53 through +58 [(1), +]. The gel mobility shift assays demonstrated that nuclear protein(s) associate with all three sp1 sites. We present data demonstrating the relative importance of the three Sp1 sites for the insulin effect: prCaM I 1835, 3.8x, delta 1081; prCaM I 392, 5.3x, delta 1055; prCaM I 180, 3.7x, delta 462; prCaM I 237, 1.6x, delta 478; prCaM I 139, 2.6x, delta 182; prCaM I 130, 2.1x, delta 194; and prCaM I 1463, negligible activity. In summary, the maximal insulin stimulation of CaM gene expression is seen when the promoter region contains at least two Sp1 sites.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Calmodulin-dependent cyclic AMP phosphodiesterase in liver plasma membranes: stimulated by insulin.

In vivo insulin consistently stimulates the plasma membrane, high-affinity (low Km) cyclic AMP phosphodiesterase (PDE) from diabetic rat liver or adipose tissue. In vitro stimulation of membrane PDE by insulin has been reported to be inconsistent. Also, the involvement of calmodulin (CaM) in insulin stimulation of PDE has been controversial. In this report, conditions for the isolation of rat liver plasma membranes containing PDE that is sensitive to in vitro insulin stimulation and the involvement of CaM in insulin stimulation of PDE were investigated. In vitro insulin raised the Vmax of the enzyme without altering its apparent Km and was dose dependent. Insulin stimulation was lost after freezing, sonication, solubilization with detergents, or storage of the membranes at 4 degrees C for 4 h after isolation. Insulin stimulation was completely blocked by the CaM antagonist compound 48/80, EGTA, or trifluoperazine. Two isoforms of membrane-bound PDE were separated by ion-exchange chromatography following solubilization of the plasma membranes. The activities of both isoforms were stimulated by exogenous CaM. Plasma membrane PDE eluted after the application of exogenous CaM plus Ca2+. The data support the concept of a critical involvement of CaM in insulin activation of liver membrane PDE.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Insulin-stimulated calmodulin gene expression in rat H-411E cells can be selectively blocked by antisense oligonucleotides.

Reduced expression of calmodulin (CaM) and decreased activity of low Km cyclic AMP (cAMP) phosphodiesterase (PDE) are associated with uncontrolled diabetes. This condition can be readily mimicked in hepatocytes cultivated in insulin-depleted medium (Solomon, et al J. Lab. Clin. Med. in press, 1994). To investigate the relationship between CaM and low Km cAMP PDE gene expression in response to insulin, we specifically blocked expression of the three CaM genes by antisense oligonucleotides under insulin-deficient and -sufficient conditions in a rat hepatoma cell line, H-411E. We observed that both the low Km cAMP PDE activity and the steady state levels of CaM mRNA were increased in response to insulin by 50 and 100%, respectively. When antisense oligonucleotide to CaM I, II or III was added to the cultures, only CaM I antisense oligonucleotide blocked insulin stimulation of both CaM I mRNA and protein with concommittant marked inhibition of insulin's expected stimulation of low Km cAMP PDE. Furthermore, in another experiment utilizing both antisense and oligonucleotide probes specific for CaM I, II, or III together, only CaM I mRNA expression was blocked. We conclude that H-411E cells respond to insulin by appropriate increases in CaM transcripts. Furthermore, the stimulatory effect of insulin on both CaM synthesis and activation of low Km cAMP PDE could be blocked by antisense to CaM I, but not II or III genes. Therefore, in addition to the above conclusions, H-411E hepatoma cells appear to be an excellent in vitro system to explore the molecular mechanisms by which CaM and low Km cAMP PDE genes are regulated in the diabetic state.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Regulation of calmodulin gene expression by insulin is both transcriptional and post-transcriptional.

Previously we demonstrated that in streptozotocin-induced or spontaneously diabetic BB rats (BB-SDR), low-Km cyclic AMP (cAMP), phosphodiesterase (PDE), and calmodulin (CaM) are decreased. Isolated fat cells of diabetic animals synthesized less CaM and contained reduced levels of CaM transcripts (Solomon SS, Palazzolo MR, Green SA, Raghow R. Biochem Biophys Res Commun 1990; 168: 1007-12). Treatment of diabetic animals with insulin restores CaM transcripts to normal. RNA was extracted from isolated hepatocytes from BB-SDR rats in primary tissue culture treated with insulin (from 2.8 x 10(4) to 1.4 x 10(6) microU/ml) for 48 hours, was immobilized on nitrocellulose, and was sequentially hybridized with radiolabeled probes for CaM, actin, and tubulin. Insulin stimulates steady state levels of mRNA for calmodulin > actin > tubulin. Furthermore, decreased steady state levels of CaM mRNA in hepatocytes from diabetic animals are restored to normal levels with in vitro insulin incubation. Data from nuclear transcription run-on assays demonstrate that insulin stimulates transcription of mRNA CaM by 80%. In addition, we observed RNA degradation in the untreated diabetic but not insulin-treated liver. These data support transcriptional as well as post-transcriptional effects of insulin on CaM mRNA. We postulate that in uncontrolled diabetes, elevations in levels of cAMP in tissue result in part from decreased activity of the apparently co-regulated PDE and CaM and that PDE inactivation in diabetes results from both insulin insufficiency and CaM down-regulation.

Actins↗
PubMed1993

Alteration of tissue vanadium content in diabetes.

A great deal of interest in the element vanadium has been generated recently because of its potential as a therapeutic agent for diabetes mellitus. Vanadium's insulin-mimetic properties and its requirement for proper growth and development suggest that it may be involved in insulin's mechanism of action. We have therefore examined vanadium levels in kidney, muscle, and liver tissues from normal and diabetic BB Wistar rats. Our results indicate that diabetes mellitus can decrease the tissue vanadium content of liver, suggesting that the trace element vanadium may be important in insulin action.

Animals↗
PubMed1992

In vivo growth hormone treatment stimulates secretion of very low density lipoprotein by the isolated perfused rat liver.

We have previously demonstrated in hepatocyte suspensions prepared after in vivo GH deprivation [hypophysectomy (hypox)] that rates of esterification of [1-14C]oleic acid into triglyceride (TG) and phospholipid (PL) were diminished, and that these esterification rates were correspondingly restored by repletion with recombinant GH. The current studies were designed to determine if GH exerts a similar effect on the secretion of very low density lipoprotein (VLDL), the primary plasma carrier of TG. We assessed rates of secretion of VLDL lipid and apoprotein by perfused livers prepared from cortisol/T3-replaced hypox female rats in the presence and absence of recombinant human (h) GH infusion. We also determined rates of synthesis and secretion of VLDL TG from infused [1-14C]oleic acid. After hypox, rates of secretion of VLDL lipid (TG, PL, and cholesterol) and apoprotein (total) were significantly decreased. In addition, VLDL secreted under these conditions was depleted of PL, relative to the other lipid components. Secretion of newly synthesized VLDL TG from [1-14C]oleic acid was also decreased; however, neither intracellular accumulation of labeled TG nor absolute tissue levels of TG were significantly changed. Conversely, GH treatment of hypox rats effectively restored rates of secretion of VLDL TG, PL, cholesterol (C) and apoprotein to control levels. These findings support the putative role of GH in regulating VLDL secretion in vivo by demonstrating that alterations in plasma GH are accompanied by changes in VLDL secretion. The findings further suggest that GH may regulate VLDL secretion by altering the amount of PL and/or apoprotein available for formation of the VLDL particle.

Animals↗
PubMed1991

Effects of sequence and timing of hormonal additions on adipose tissue: activation of low-Km cyclic adenosine monophosphate phosphodiesterase.

Epinephrine (EPI) is lipolytic and insulin (INS) antilipolytic in the isolated fat cell (IFC). We have previously demonstrated that in a perifusion system the antilipolytic action of INS is more powerful when IFC are exposed to INS before EPI. In contrast to their opposite effects on lipolysis, both INS and EPI stimulate low-Km cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) in adipose tissue. In view of these observations, we decided to determine the effects of sequential addition of EPI and INS on stimulation of PDE from rat adipose tissue. Using previously published methods, the effects of INS and EPI on PDE were assessed alone, together with INS followed by EPI, and then with EPI followed by INS. The resulting data demonstrate that EPI and INS individually both stimulate PDE (P less than .001); EPI plus INS together stimulate PDE minimally compared with EPI or INS alone (P less than .001); when adipose tissue is included with INS first, then followed by EPI, activation of PDE is much less than INS or EPI alone (P less than .001); and when adipose tissue is stimulated by EPI then INS, there is no activation of PDE, different from EPI or INS alone (P less than .001). In conclusion, in perifused IFC, INS and EPI always oppose each other. In studies using activation of PDE, EPI and INS each stimulate PDE, but INS opposes EPI when incubated simultaneously. When adipose tissue is incubated first with INS followed by EPI, PDE is activated. In contrast, when the reverse order is applied, no activation of PDE is observed.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗