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Biomedical subjects

S Rajagopalan

Publications and source records attributed to S Rajagopalan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Spontaneous coronary artery dissection in a pregnant woman.

BACKGROUND: Spontaneous coronary dissection is a rare condition occurring more often in women, with a higher frequency during the peripartum period. No specific etiology has been defined to describe this uncommon, yet often fatal phenomenon. CASE: A young woman presented at 36 weeks of a noncomplicated pregnancy with recent onset of diaphoresis, dyspnea, and tingling substernal chest discomfort. Upon evaluation, she developed cardiovascular collapse and ventricular fibrillation requiring aggressive resuscitative measures, eventually leading to extracorporeal membrane oxygenation. Right coronary artery dissection was ultimately diagnosed and treated with intracoronary angioplasty and stent placement. CONCLUSION: Spontaneous coronary dissection must be considered when evaluating a patient with a similar clinical presentation, given its overall mortality of more than 50% at presentation, particularly in the peripartum period.

Adult↗
PubMed2001

Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158).

The killer cell immunoglobulin-like receptor (KIR) family includes receptors that bind to HLA class I molecules on target cells and inhibit natural killer (NK)-cell cytotoxicity, and receptors such as KIR3DL7 with no known ligand and function. Inhibitory KIR recruit the tyrosine phosphatase SHP-1 to block signals transduced by any one of a number of activation receptors. Inhibition of overall protein tyrosine phosphorylation by SHP-1 during binding of KIR to MHC class I on target cells is selective, suggesting that a limited number of substrates are dephosphorylated by SHP-1. We have chosen to study KIR inhibition as it occurs during binding of KIR to MHC class I on target cells, despite the technical limitations inherent to studies of processes regulated by cell contact. KIR binding to MHC class I on target cells inhibits tyrosine phosphorylation of the activation receptor 2B4 (CD244) and disrupts adhesion of NK cells to target cells. Inhibition of proximal events in NK activation may increase the availability of NK cells by liberating them from non-productive interactions with resistant target cells. As the receptors and the signaling pathways that induce NK cytotoxicity are not fully characterized, elucidation of the inhibitory mechanism employed by KIR may provide insight into NK activation.

Amino Acid Sequence↗
PubMed2000

Selecting a longitudinal pathway: Robo receptors specify the lateral position of axons in the Drosophila CNS.

On each side of the midline of the Drosophila CNS, axons are organized into a series of parallel pathways. Here we show that the midline repellent Slit, previously identified as a short-range signal that regulates midline crossing, also functions at long range to pattern these longitudinal pathways. In this long-range function, Slit signals through the receptors Robo2 and Robo3. Axons expressing neither, one, or both of these receptors project in one of three discrete lateral zones, each successively further from the midline. Loss of robo2 or robo3 function repositions axons closer to the midline, while gain of robo2 or robo3 function shifts axons further from the midline. Local cues further refine the lateral position. Together, these long- and short-range guidance cues allow growth cones to select with precision a specific longitudinal pathway.

Animals↗
PubMed2000

Tuberculosis in the elderly.

Tuberculosis (TB) today remains one of the world's most lethal infectious diseases. An estimated one-third of the world's population is infected with the tubercle bacillus-Mycobacterium tuberculosis (Mtb), and 7 to 8 million people develop TB disease each year (27). For purpose of clarity, TB infection (latent TB) is defined as harboring Mtb without evidence of active infection, and TB disease is active infection without Mtb based on clinical and laboratory findings. Recognizing that TB has been one of the most neglected international health problems and that the TB epidemic is rampant in many parts of the world, the World Health Organization (WHO) declared TB to be a global health emergency in 1993 (23). Despite the steady decline in TB cases since this time resulting from the overall implementation of more effective infection control practices, directly observed therapy (DOT), and efforts to control the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) epidemic, preventive and control strategies among other high-risk populations such as the elderly evidently remain a clinical and epidemiological challenge. The geriatric population among all ethnic groups and both genders, represent the largest reservoir of TB infection, particularly in developed nations (9). Clinical features of TB in older adults may be atypical, non-specific, and confused with concomitant age-related diseases (28). Underlying acute or chronic diseases, malnutrition, and the biological changes with aging, can disrupt integumental barriers, impair microbial clearance mechanisms, and contribute to the expected age-associated decline in cellular immune responses to infecting agents such as Mtb. Diagnosis of TB can be difficult and consequently overlooked; this treatable infection may unfortunately be recognized only at autopsy. Furthermore, therapy of TB in the elderly is challenging because of the increased incidence of adverse drug reactions. Optimal treatment of associated chronic diseases, minimization of invasive procedures, limitation of polypharmacy, and adequate nutritional support are essential for this vulnerable population. The institutionalized elderly in addition are especially at high risk for reactivation of latent TB as well as susceptible to new TB infection. This article will discuss the global epidemiology, pathogenesis and immunologic aspects, unique clinical consideration, treatment and prevention of TB, briefly inclusive of the recent published guidelines for targeted tuberculin testing and treatment of latent TB infection as it pertains to the elderly.

Aged↗
PubMed2000

Carotid artery vasoreactivity in response to sympathetic stress correlates with coronary disease risk and is independent of wall thickness.

OBJECTIVES: We designed a study to determine the carotid artery (CA) response to sympathetic activity and to determine whether the response correlates with coronary risk and is independent of wall thickness (IMT). BACKGROUND: Brachial artery reactivity in response to wall stress correlates with coronary risk and coronary disease (CAD). The reactivity of the CA, which is susceptible to atherosclerosis, has not been evaluated. METHODS: The change in diameter of the CA (deltaCAdiam) during a cold pressor test and after nitroglycerin and IMT were measured with ultrasound in 93 men and women at average risk, high risk and with CAD. RESULTS: At 90 s during a cold pressor test average-risk subjects increased CAdiam by 7.9+/-3.3%, which was significantly less in the high-risk group (1.5+/-1.8%), and vasoconstriction occurred in the group of subjects with CAD (-6.9+/-2.7%) (p < 0.01 for comparisons). There were no differences in response to nitroglycerin. Coronary risk was an independent predictor of the %deltaCAdiam (p < 0.0001). Wall thickness, age, systolic pressure and triglycerides each correlated negatively, and high-density lipoprotein cholesterol correlated positively with %deltaCAdiam. The major variable associated with the %deltaCAdiam, was group (p = 0.0001). After adjusting for smoking, age and high-density lipoprotein cholesterol, there was no association between the %deltaCAdiam, and IMT and %deltaCAdiam, but not IMT, was predictive of groups. CONCLUSIONS: The CA response to a sympathetic stimulus is altered in the presence of coronary risk factors and CAD and appears to reflect endothelial function independent of IMT. Carotid artery reactivity may be a valuable adjunctive noninvasive method to assess coronary risk.

Adult↗
PubMed2000

Crossing the midline: roles and regulation of Robo receptors.

In the Drosophila CNS, the midline repellent Slit acts at short range through its receptor Robo to control midline crossing. Longitudinal axons express high levels of Robo and avoid the midline; commissural axons that cross the midline express only low levels of Robo. Robo levels are in turn regulated by Comm. Here, we show that the Slit receptors Robo2 and Robo3 ensure the fidelity of this crossing decision: rare crossing errors occur in both robo2 and robo3 single mutants. In addition, low levels of either Robo or Robo2 are required to drive commissural axons through the midline: only in robo,robo2 double mutants do axons linger at the midline as they do in slit mutants. Robo2 and Robo3 levels are also tightly regulated, most likely by a mechanism similar to but distinct from the regulation of Robo by Comm.

Animals↗
PubMed2000

Tuberculosis in long-term-care facilities.

The geriatric population represents the largest reservoir of Mycobacterium tuberculosis infection in developed nations, including the United States. Tuberculosis (TB) case rates in the United States are highest for this age group compared with other age categories. The subtle clinical manifestations of TB in the elderly often can pose potential diagnostic dilemmas and therapeutic challenges, resulting in increased morbidity and mortality in this age group; this treatable infection unfortunately often is detected only at autopsy. Compared with their community-dwelling counterparts, the institutionalized elderly are at a greater risk both for reactivation of latent TB and for the acquisition of new TB infection. Prevention and control of TB in facilities providing long-term care to the elderly thus cannot be overemphasized.

Aged↗
PubMed1999

S. pombe Pbh1p: an inhibitor of apoptosis domain containing protein is essential for chromosome segregation.

Proteins containing the baculovirus inhibitor of apoptosis repeats (BIR domains) have been identified in a wide range of species. BIR domain containing proteins are thought to inhibit caspases and thereby cause inhibition of apoptosis. A BIR domain containing protein has been recently identified by the Schizosaccharomyces pombe genome sequencing project. However, caspase-like proteins have not been found in yeasts, suggesting that the BIR domain containing proteins might play a fundamental role in cell regulation, in addition to their well-characterized role in inhibition of apoptosis. In this study, we have characterized Pbh1p, an S. pombe BIR domain containing protein. Construction and analysis of a null mutant in pbh1+ revealed that pbh1+ is essential for cell viability. Moreover, cells devoid of Pbh1p are defective in chromosome condensation and chromosome segregation. Thus, proper chromosome segregation requires the function of Pbh1p. Over-production of Pbh1p led to abnormalities in mitosis and cytokinesis, suggesting that the levels of Pbh1p are important for regulation of mitosis and cytokinesis.

Amino Acid Sequence↗
PubMed1999

A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells.

Human natural killer (NK) cells express several killer cell immunoglobulin (Ig)-like receptors (KIRs) that inhibit their cytotoxicity upon recognition of human histocompatibility leukocyte antigen (HLA) class I molecules on target cells. Additional members of the KIR family, including some that deliver activation signals, have unknown ligand specificity and function. One such KIR, denoted KIR2DL4, is structurally divergent from other KIRs in the configuration of its two extracellular Ig domains and of its transmembrane and cytoplasmic domains. Here we show that recombinant soluble KIR2DL4 binds to cells expressing HLA-G but not to cells expressing other HLA class I molecules. Unlike other HLA class I-specific KIRs, which are clonally distributed on NK cells, KIR2DL4 is expressed at the surface of all NK cells. Furthermore, functional transfer of KIR2DL4 into the cell line NK-92 resulted in inhibition of lysis of target cells that express HLA-G, but not target cells that express other class I molecules including HLA-E. Therefore, given that HLA-G expression is restricted to fetal trophoblast cells, KIR2DL4 may provide important signals to maternal NK decidual cells that interact with trophoblast cells at the maternal-fetal interface during pregnancy.

Cell Membrane↗
PubMed1999

Membrane anchoring of calnexin facilitates its interaction with its targets.

Calnexin, a chaperone that resides in the endoplasmic reticulum, participates in the quality control function of this compartment. Many glycoproteins in the process of folding associate transiently with this chaperone via interactions involving the recognition of their mono-glucosylated glycans. Some misfolded proteins which are retained in the endoplasmic reticulum exhibit prolonged association with calnexin. We have examined whether the transmembrane and cytoplasmic domains of calnexin influence the association of this chaperone with its targets. Interactions of wild type and truncated calnexin with a glycoprotein that is retained in the endoplasmic reticulum (the lymphocyte tyrosine kinase, Ltk), with membrane IgM heavy chains, and with the MHC class I heavy chain protein were investigated. A soluble calnexin molecule lacking the transmembrane domain and cytoplasmic tail does not associate with any of these proteins. When a heterologous transmembrane domain is fused to the lumenal portion of calnexin, this membrane-bound protein can bind Ltk, IgM heavy chains, and MHC class I heavy chain proteins. These results suggest that calnexin must be membrane-anchored in order to recognize its substrates.

Animals↗
PubMed1999

Practice guidelines and late-life depression assessment in long-term care.

To determine how well nursing home physicians believe they can detect and treat depression, we conducted a national survey, eliciting a 63% response rate. More than 75% of respondents believed they detected and treated depression well. Excellent depression training (vs "good," "fair," "poor/none") was associated with better self-reported recognition (odds ratio [OR] 14.25; 95% confidence interval [CI] 1.81, 111.93) and treatment skills (OR 6.72; 95% CI 1. 91, 23.64). Screening tool use predicted greater self-assessed detection (OR 1.89; 95% CI 0.92, 3.87) and treatment competency (OR 2.00; 95% CI 1.14, 3.50). Practice guideline awareness was associated with greater self-reported treatment competency (OR 2.47; 95% CI 1.56, 3.91).

Chi-Square Distribution↗
PubMed1998

Zinc bound to the killer cell-inhibitory receptor modulates the negative signal in human NK cells.

The lysis of target cells by human NK cells is inhibited by several kinds of receptors with varying specificities for the MHC class I molecules of target cells. The requirements for complete inhibition of NK cytotoxicity appear to be complex and not well defined. The HLA-C-specific members of the killer cell-inhibitory receptor (KIR) family, carrying two Ig domains (KIR2D), are unusual among Ig superfamily members in their ability to bind zinc. A role for the zinc-binding site in KIR-mediated inhibition was demonstrated in this study using a functional reconstitution system in NK cells. Replacement of six histidines by alanine residues in putative zinc binding sites of a KIR2D ablated zinc binding and markedly impaired its inhibitory function, but left intact its ability to bind HLA-C and to transduce a positive signal through an immunoreceptor tyrosine-based activation motif grafted onto its cytoplasmic tail. Thus, zinc modulates specifically the negative signal transmitted by this KIR molecule. Mutation of an exposed amino-terminal zinc-binding motif alone was sufficient to impair the inhibitory function of KIR. The data suggest that complete inhibition of HLA-C-specific NK cells requires a zinc-dependent protein-protein interaction via the amino-terminal end of KIR2D.

Binding Sites↗
PubMed1997

The direct binding of a p58 killer cell inhibitory receptor to human histocompatibility leukocyte antigen (HLA)-Cw4 exhibits peptide selectivity.

Natural killer (NK) cells in mice and humans express a number of structurally diverse receptors that inhibit target cell lysis upon recognition of major histocompatibility complex (MHC) class I molecules expressed on targets. The contribution of peptide to the structural features of class I required for NK cell inhibition appears to vary depending on the type of receptor engaged. Thus, while there is no peptide specificity in NK inhibition mediated by Ly-49A in the mouse, human histocompatibility antigen (HLA)-B*2705-specific NK clones displayed selectivity for peptides. In this report, we examine the role of peptide in the recognition of HLA-C by the defined killer cell inhibitory receptor (KIR) cl42 with established specificity for HLA-Cw4. Binding of soluble KIR cl42 molecules to HLA-Cw4 expressed on transporter associated with antigen presentation (TAP)-deficient RMA-S cells occurred only upon exogenous peptide loading. Moreover, there was peptide selectivity in that certain substitutions at positions 7 and 8 of the nonamer peptide QYDDAVYKL abolished Cw4 interaction with KIR cl42 despite similar surface expression of HLA-C. The specificity of this direct interaction between peptide-loaded HLA-Cw4 on RMA-S cells and soluble KIR cl42 correlated with recognition by NK clones in that they were inhibited only by HLA-Cw4 loaded with the appropriate peptides.

Amino Acid Sequence↗
PubMed1997

Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension.

BACKGROUND: The major source of superoxide (.O2-) in vascular tissues is an NADH/NADPH-dependent, membrane-bound oxidase. We have previously shown that this oxidase is activated in angiotensin II-but not norepinephrine-induced hypertension. We hypothesized that hypertension associated with chronically elevated angiotensin II might be caused in part by vascular .O2- production. METHODS AND RESULTS: We produced hypertension in rats by a 5-day infusion of angiotensin II or norepinephrine. Rats were also treated with liposome-encapsulated superoxide dismutase (SOD) or empty liposomes. Arterial pressure was measured in conscious rats under baseline conditions and during bolus injections of either acetylcholine or nitroprusside. Vascular .O2- production was assessed by lucigenin chemiluminescence. In vitro vascular relaxations were examined in organ chambers. Norepinephrine infusion increased blood pressure to a similar extent as angiotensin II infusion (179 +/- 5 and 189 +/- 4 mm Hg, respectively). In contrast, angiotensin II-induced hypertension was associated with increased vascular .O2- production, whereas norepinephrine-induced hypertension was not. Treatment with liposome-encapsulated SOD reduced blood pressure by 50 mm Hg in angiotensin II-infused rats while having no effect on blood pressure in control rats or rats with norepinephrine-induced hypertension. Similarly, liposome-encapsulated SOD enhanced in vivo hypotensive responses to acetylcholine and in vitro responses to endothelium-dependent vasodilators in angiotensin II-treated rats. CONCLUSIONS: Hypertension caused by chronically elevated angiotensin II is mediated in part by .O2-, likely via degradation of endothelium-derived NO. Increased vascular .O2- may contribute to vascular disease in high renin/angiotensin II states.

Acetylcholine↗
PubMed1997

Prospective analysis of genital ulcer disease in Brooklyn, New York.

We prospectively studied 82 men and women with first episodes of genital ulceration. By using newer diagnostic techniques, a definite microbial etiology of 84 infections in 65 of the 82 patients evaluated was found. There were 33 cases of definite primary syphilis, 27 of definite chancroid, and 24 of definite genital herpes simplex. Conclusive evidence of more than one microbial etiology was found for 19 (23%) of the patients. Simultaneous primary syphilis and chancroid was the third most common ulcer infection. This finding underscores the need for both clinical suspicion of multiple infections in patients with genital ulcers and comprehensive testing for all suspicious etiologies.

Adolescent↗