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Biomedical subjects

R Garg

Publications and source records attributed to R Garg.

At least 73 records · Page 4Linked to original sources
PubMed1999

Increased IkappaB expression and diminished nuclear NF-kappaB in human mononuclear cells following hydrocortisone injection.

We have recently demonstrated that hydrocortisone and other glucocorticoids inhibit reactive oxygen species (ROS) generation by mononuclear (MNC) and polymorphonuclear leucocytes (PMNL). Since NF-kappaB/IkappaB system regulates the transcription of proinflammatory genes, including those responsible for ROS generation, we tested the hypothesis that hydrocortisone may stimulate IkappaB production thus inhibiting NF-kappaB translocation from the cytosol into the nucleus in MNC, in vivo. One hundred milligram of hydrocortisone was injected intravenously into 4 normal subjects. Blood samples were obtained prior to the injection and at 1, 2, 4, 8 and 24 hr after the injection. Nuclear extracts and total cell lysates were prepared from MNC by standard techniques. IkappaB levels in MNC homogenates increased at 1 hr, peaked at 2-4 hr, started to decrease at 8 hr, and returned to baseline levels at 24 hr. NF-kappaB in MNC nuclear extracts decreased at 1 hr, reached a nadir at 4 hr, gradually increased at 8 hr and returned back to baseline levels at 24 hr. The total protein content of NF-kappaB subunit (P65) in MNC lysates also showed a decrease following hydrocortisone injection. This decrease was observed at 2 hr, reached a nadir at 4 hr, and returned to baseline levels at 24 hr. ROS generation inhibition paralleled NF-kappaB levels in the nucleus. It was inhibited at 1 hr, reached a nadir at 2-4 hr, started to increase at 8 hr, and returned to basal levels at 24 hr. Our data demonstrate that hydrocortisone induces IkappaB and suppresses NF-kappaB expression in MNC in parallel. IkappaB further reduces the translocation of NF-kappaB into the nucleus thus preventing the expression of proinflammatory genes.

Adult↗
PubMed1998

Quantitative structure-activity relationships (QSAR) for 9-anilinoacridines: a comparative analysis.

A new analysis of the quantitative structure-activity relationship (QSAR) of the antitumor activity of anilinoacridines against L1210 leukemia in mice and mouse toxicity is reported. QSAR have also been derived for the inhibitory activity of the anilinoacridines with tumor cells and their binding to DNA. These results are compared with reactivity with simple nucleophiles. The comparative analysis shows the importance of electron releasing substituents (in general negative coefficients with the Hammett parameter sigma+) throughout the various systems and the complete lack of hydrophobic interactions from DNA to cells to mice. The presence of steric terms suggests that a protein receptor is involved. The study shows that QSAR has an important role to play in improving the efficiency in the design of bioactive compounds and that care must be taken in the design of a set of congeners so that the necessary parameters are available to do the QSAR analysis. Our study illustrates the value of comparative QSAR in generalizing our understanding of chemical-biological interactions.

Amsacrine↗
PubMed1998

Temporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995.

BACKGROUND: Evidence from clinical trials in the past decade has consistently shown that angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with congestive heart failure (CHF). The extent to which clinical practice has adopted ACE inhibitor therapy is unknown. METHODS: The Cardiovascular Health Study is a prospective observational study of 5201 community-dwelling adults aged 65 years and older. Prevalent CHF cases were identified on study entry (from June 10, 1989, through May 31, 1990) and incident CHF cases were identified throughout 5 years of follow-up. Medication data were collected from annual medication inventories. The percentage of patients with CHF using ACE inhibitors was calculated at each annual examination. Temporal trends in CHF treatment with ACE inhibitors between June 10, 1989, through May 31, 1990, and June 1, 1994, through May 31, 1995, were analyzed. RESULTS: Use of ACE inhibitors to treat CHF increased slightly over time among prevalent cases at each annual examination: 26% of prevalent CHF cases were treated in 1989-1990 compared with 36% of prevalent cases in 1994-1995. This 10% increase was statistically significant (P<.01). Participants with low ejection fractions were 2 times more likely to be treated with ACE inhibitors than were those with normal ejection fraction and this tendency did not change over time. Among cases newly diagnosed in the year before the 1990-1991 examination, 42% were using ACE inhibitors; among those newly diagnosed in the year before 1994-1995, 40% were using ACE inhibitors. This 2% decrease was not statistically significant (P=.68). CONCLUSION: These findings suggest that, while the medical management of CHF with ACE inhibitors has increased modestly over time in prevalent cases, these drugs may still be underused, especially among incident cases.

Aged↗
PubMed1998

The relationship between cardiothoracic ratio and left ventricular ejection fraction in congestive heart failure. Digitalis Investigation Group.

BACKGROUND: Left ventricular ejection fraction (EF) is a valuable prognostic index in patients with congestive heart failure (CHF). Although EF can be readily measured, many clinicians use roentgenographic heart size as a clue to differentiate systolic from diastolic dysfunction, even in the absence of solid supportive data. OBJECTIVE: To test the hypothesis that the cardiothoracic ratio (CTR) measured from the chest roentgenogram can be used to estimate left ventricular EF in individuals with CHF. METHODS: To answer this question, the database of the Digitalis Investigation Group trial was used. The CTR, determined using the Danzer method, and quantitative EF, measured locally using angiographic, radionuclide, or 2-dimensional echocardiographic techniques, were compared in 7476 patients with clinical CHF (New York Heart Association functional classes I-IV) due to acquired left-sided cardiac disease of ischemic, hypertensive, idiopathic, and alcohol-related causes. RESULTS: Mean (+/-SD) CTR for the cohort was 0.53+/-.07. Mean (+/-SD) EF was 31.7%+/-12.2%. A weak, negative correlation between CTR and EF was observed (r=-0.176). Similar findings were obtained when the results were stratified by cause of CHF, presence of clinically defined right ventricular dysfunction, and method of EF measurement. Categorical analysis failed to yield a CTR cutoff point that facilitated useful segregation of individuals with an EF greater than 35% or 35% and below; greater than 40% or 40% and below; and greater than 45% or 45% and below in any patient group. CONCLUSIONS: Although a weak, negative correlation exists between CTR and EF, this relationship does not allow for accurate determination of systolic function in individual patients with CHF. Considering the morbidity and mortality associated with CHF, and the clinical implications of systolic function in this syndrome, direct measurement of EF is recommended.

Aged↗
PubMed1998

Regulation of TNF-alpha-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells.

We have investigated the role of the small guanosine-trisphosphate (GTP)-binding proteins, Rho, Rac, and Cdc42, in the early responses of human umbilical vein endothelial cells (HUVECs) to TNF-alpha (tumor necrosis factor-alpha). Quiescent confluent HUVECs incubated with TNF-alpha for 5-30 min showed an increased formation of membrane ruffles, filopodia, and actin stress fibres followed by cell retraction and formation of intercellular gaps. This process was accompanied by the dispersion of cadherin-5 from intercellular junctions. TNF-alpha also induced a transient increase in polymerized F-actin, as determined both by measuring G-actin content and by quantifying fluorescent emission from fluorescein isothiocyanate (FITC)-phalloidin-labelled F-actin. Microinjection of cells with activated RhoA protein led to an increase in polymerized actin, formation of stress fibres, cell retraction as well as dispersion of cadherin-5. The proteins Cdc42 and Rac induced qualitatively similar effects to Rho, although not as dramatic and in addition induced formation of filopodia and lamellipodia. Microinjection of cells with a Rho inhibitor, C3 transferase, prevented gap formation caused by TNF-alpha. Similar effects were observed in cells microinjected with the dominant inhibitory proteins N17Cdc42 and N17Rac1. Cell retraction and gap formation were also prevented by inhibitors of myosin light chain kinase (MLCK). Our data suggest that Cdc42, Rac, and Rho are activated in a hierarchical cascade following stimulation with TNF-alpha leading to actomyosin-mediated cell retraction and formation of intercellular gaps.

ADP Ribose Transferases↗
PubMed1998

Quantitative structure-activity relationship studies on cyclic urea-based HIV protease inhibitors.

A quantitative structure-activity relationship (QSAR) study is described on some cyclic ureas that inhibit the enzyme HIV-1 protease (HIV-1-PR) and exhibit antiviral potency. Both the enzyme inhibition activity and the antiviral potency were found to be primarily governed by the hydrophobic property of the substituents at the nitrogens (N2/N2') of the urea. Adjacent to the nitrogens, the C1/C1'-substituents are, however, found to affect the activity (inhibition) by their molecular size. The essential binding of the ureas with the receptor is, however, through multiple hydrogen bonding, where the substituents, too, can participate in such binding if they are capable of doing so. A schematic diagram of the overall interaction of the inhibitors with the receptor is presented.

HIV Protease Inhibitors↗
PubMed1997

Perceived risks to independent living: the views of older, community-dwelling adults.

The purpose of the present study was to gather the perceptions of older, community-dwelling adults about factors they considered essential for them to remain living within the community. In-depth interviews were conducted with 103 men and women over the age of 65 years who were living in their own home or apartment, within an urban center. Factors such as finances, health, family support, a sense of identity, and a feeling of independence were perceived by older adults to contribute to their ability to remain living in the community. Importantly, older adults viewed threats to this continued independent living as both (a) factors connected to losses and maintenance of capability, but also (b) as impediments to further growth of their personal well-being.

Activities of Daily Living↗
PubMed1997

Adenosine deaminase activity in nephrotic syndrome.

Cell-mediated immunity (CMI) was evaluated in 40 children with idiopathic nephrotic syndrome and 20 healthy controls. The significantly decreased response to purified protein derivative (PPD)(P < 0.001), absolute lymphocyte count (ALC) (P < 0.02), T-lymphocytes percentage (P < 0.001) and elevated serum adenosine daminase (ADA) activity (P < 0.001) were observed in patients with active nephrotic syndrome (ANS) in comparison to controls. The overall mean values of T-lymphocytes percentage and ADA activity in ANS patients were 73.7 and 213.7 per cent of normal mean, respectively. A significant negative correlation was observed between the two parameters (r = -0.5649, P < 0.001). In remission, the ALC and T-lymphocytes percentage showed significant increase in levels in comparison to their corresponding ANS values (P < 0.05 and P < 0.001, respectively), but the latter remained significantly lower when compared with controls (P < 0.001). The ADA activity did not differ significantly in comparison to corresponding ANS level. Thus, impaired CMI was observed both in active, as well as in remission stage of the disease and ADA activity demonstrated a more pronounced change than other parameters.

Adenosine Deaminase↗
PubMed1997

Immunoglobulins and circulating immune complexes in nephrotic syndrome.

Serum immunoglobulin (IgG, IgA and IgM) levels were measured in 40 children with idiopathic nephrotic syndrome and 20 healthy controls. Significantly decreased IgG (P < 0.001), normal IgA and increased IgM (P < 0.05), averaging 92 per cent, 99 per cent and 104 per cent of normal mean, respectively, were observed in active nephrotic syndrome (ANS). The mean immunoglobulin levels did not differ significantly among different subgroups of ANS cases. In remission, a significant increase in IgG (P < 0.01), a decrease in IgA (P < 0.05) and in IgM (P < 0.01) levels were found in comparison to their corresponding ANS values. Their concentrations were significantly abnormal also when compared with controls. The circulating immune complexes (CIC), detected by polyethylene glycol (PEG) per cent index, demonstrated that overall mean serum level was significantly higher (P < 0.01, 168 per cent of normal) in ANS patients. Among different subgroups, the mean level was significantly elevated (P < 0.001, 205 per cent of normal) only in relapsing nephrotic syndrome cases. Thus, the abnormal levels of immunoglobulins were found both in active as well as in remission stage of the disease, while elevated levels of CIC were seen only in patients with relapse.

Antigen-Antibody Complex↗
PubMed1997

Quantitative structure-activity relationship studies on some viral reverse transcriptase inhibitors acting as anti-HIV-1 agents.

The anti-HIV-1 and cytotoxic activities of some viral reverse transcriptase inhibitors, namely the analogues of [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranosyl]]-3'-spiro-5" -[4"-amino-1",2"-oxathiole 2",2"-dioxide] (TSAO) pyrimidine and pyrimidine modified-nucleotides, are analysed in relation to their physicochemical and molecular properties. The antiviral activities of the compounds are found to be significantly correlated with hydrophobic and electronic properties of the molecules, but no physicochemical parameters were found to be correlated with the cytotoxic effects of the compounds. This difference is exploited to improve the selectivity of the compounds. It is observed that TSAO can provide potent anti-HIV-1 drugs with a disubstituted thymine ring, in which a substituent may be at the N3-position. The disubstitution reduces the cytotoxicity, and substituents' hydrophobicity and electron donating character enhance the antiviral activity.

Anti-HIV Agents↗
PubMed1997

Quantitative structure-activity relationship studies on some anti-human-immunodeficiency-virus-1 (anti-HIV-1) drugs: viral reverse transcriptase inhibitors.

The anti-HIV-1 activity of some 3-[(benzoxazol-2-ylmethyl)amino]-, 3-[(benzoxazol-2-yl)ethyl]-, 3-[N-(phthalimidomethyl)amino]- and 3-[N-(phthalimido)ethyl]-5-ethyl-6-methyl pyridin-2(1H)-one derivatives, that have been found to elicit their action through the allosteric inhibition of the enzyme viral reverse transcriptase (VRT), have been analysed in relation to the physicochemical properties of the molecules. Significant correlations were obtained between the activity and the hydrophobic and electronic constants of substituents and van der Waals' volume of the linker chain. Based on these findings the mechanism of action of these drugs is discussed.

Anti-HIV Agents↗
PubMed1996

Etiology and characteristics of congestive heart failure in blacks.

In this study of 301 black patients with congestive heart failure (CHF), systemic hypertension is the most common cause of CHF and is the primary etiology of CHF in 61%. Left ventricular hypertrophy is highly prevalent and is seen in 63% of the patients who had an echocardiogram.

Aged↗
PubMed1996

Production and secretion of transforming growth factor beta (TGF-beta) by the human lacrimal gland.

PURPOSE: Transforming growth factor beta (TGF-beta) isoforms 1 and 2 have recently been detected in stimulated human tear fluid. The purpose of this study was to determine if these TGF-sbeta are produced and secreted by the lacrimal gland. METHODS: To accomplish this, reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect expression of TGF-beta1 and TGF-beta2 mRNAs in normal human and rabbit lacrimal gland biopsies. Northern blot analyses were used for comparing the relative levels of expression of these TGF-beta mRNAs in rabbit lacrimal glands. Human lacrimal gland biopsies were evaluated by immunohistochemistry for production of TGF-beta1, TGF-beta1 latency associated peptide (LAP), and TGF-beta2 proteins. Supernatants of unstimulated and carbachol-stimulated human lacrimal gland explant cultures were evaluated for secretion of TGF-beta1 and TGF-beta2 by ELISA: RESULTS: TGF-beta1 and TGF-beta2 mRNA expression was found in all human and rabbit lacrimal gland specimens by RT-PCR. A greater level of expression of TGF-beta1 than TGF-beta2 mRNA in the rabbit lacrimal gland was noted by Northern blot. In human lacrimal gland biopsies, TGF-beta1 and TGF-beta1 LAP were detected in acinar and ductal epithelia by immunohistochemistry. TGF-beta2 specific antibodies stained a small percentage of acinar and ductal epithelia, as well as material within the lumens of tubulo-acinar complexes in one-third of these glands. TGF-beta1 was detected in supernatants of human lacrimal gland explants, and the concentration of TGF-beta1 increased by an average of 280% after carbachol-stimulation (p = 0.004). TGF-beta2 could not be detected in unstimulated or stimulated human lacrimal gland supernatants. CONCLUSIONS: The results of these experiments indicate that TGF-beta1 and TGF-beta2 are produced by and TGF-beta1 is secreted by the human lacrimal gland. They also suggest that the lacrimal gland may be one source of TGF-beta in human tear fluid.

Adolescent↗
PubMed1996

Quantitative structure-activity relationship studies on anti-HIV-1 TIBO derivatives as inhibitors of viral reverse transcriptase.

The anti-human-immunodeficiency-virus (HIV-1) activity of the derivatives of 4,5,6,7-tetrahydro-5-methylimidazo [4,5,1-jk] [1,4] benzodiazepin-2(1H)-one (TIBO) that have been found to elicit their action through the allosteric inhibition of the enzyme viral reverse transcriptase (VRT) is analysed in relation to the physicochemical properties of the molecules. Significant correlations are obtained between the activity and the hydrophobic constant and some dummy parameters of substituents. Based on these findings, the mechanism of action of these anti-HIV drugs is discussed.

Anti-HIV Agents↗
PubMed1995

Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials.

OBJECTIVE: To evaluate the effect of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients with symptomatic congestive heart failure. DATA SOURCE AND STUDY SELECTION: Data were obtained for all completed, published or unpublished, randomized, placebo-controlled trials of ACE inhibitors that were at least 8 weeks in duration and had determined total mortality by intention to treat, regardless of sample size. Trials were identified based on literature review and correspondence with investigators and pharmaceutical firms. DATA EXTRACTION: Using standard tables, data were extracted by one author and confirmed where necessary by the other author or the principal investigator of the trial. Unpublished data were obtained by direct correspondence with the principal investigator of each study or pharmaceutical firm. DATA SYNTHESIS: The data for each outcome were combined using the Yusuf-Peto adaptation of the Mantel-Haenszel method. Overall, there was a statistically significant reduction in total mortality (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.67 to 0.88; P < .001) and in the combined endpoint of mortality or hospitalization for congestive heart failure (OR, 0.65; 95% CI, 0.57 to 0.74; P < .001). Similar benefits were observed with several different ACE inhibitors, although the data were largely based on enalapril maleate, captopril, ramipril, quinapril hydrochloride, and lisinopril. Reductions for total mortality and the combined endpoint were similar for various subgroups examined (age, sex, etiology, and New York Heart Association class). However, patients with the lowest ejection fraction appeared to have the greatest benefit. The greatest effect was seen during the first 3 months, but additional benefit was observed during further treatment. The reduction in mortality was primarily due to fewer deaths from progressive heart failure (OR, 0.69; 95% CI, 0.58 to 0.83); point estimates for effects on sudden or presumed arrhythmic deaths (OR, 0.91; 95% CI, 0.73 to 1.12) and fatal myocardial infarction (OR, 0.82; 95% CI, 0.60 to 1.11) were less than 1 but were not significant. CONCLUSIONS: Total mortality and hospitalization for congestive heart failure are significantly reduced by ACE inhibitors with consistent effects in a broad range of patients.

Aged↗
PubMed1995

Ascitic fluid cholesterol in malignant and tubercular ascites.

Cholesterol was estimated in ascitic fluid of 44 patients (29 malignant and 15 tubercular). Mean ascitic cholesterol level was significantly higher in malignant ascites (89.52 mg/dl) as compared to tubercular ascites (35.07 mg/dl). At a cut off value of 54.5 mg/dl (mean in tubercular ascites + 2SD), the sensitivity, specificity, positive and negative predictive value and overall diagnostic accuracy for differentiating malignant from tubercular ascites was found to be 89.65%, 100%, 100%, 83.33% and 93.18% respectively. Ascitic fluid cholesterol estimation is a reliable and simple test for differentiating malignant ascites from tubercular ascites.

Adult↗