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Biomedical subjects

R Nagarajan

Publications and source records attributed to R Nagarajan.

At least 19 recordsLinked to original sources
PubMed2001

Paris-Trousseau syndrome platelets in a child with Jacobsen's syndrome.

The thrombocytopenia in an infant with clinical features of Jacobsen's syndrome characterized by multiple congenital anomalies, cardiac defects, psychomotor retardation, and deletion of chromosome 11 at 11q23.3 has been evaluated. Study of his platelets in the electron microscope revealed giant alpha granules in his cells identical in appearance to those reported in the family with Paris-Trousseau syndrome. As a result, the Paris-Trousseau syndrome appears to be a variant of the Jacobsen syndrome, and the thrombocytopenia observed in all cases of chromosome 11q23.3 deletion due to dysmegakaryopoieses. Giant alpha granules are frequently observed in normal platelets during long-term storage and may form in Jacobsen and Paris-Trousseau platelets during prolonged residence in the bone marrow.

Abnormalities, Multiple↗
PubMed2001

EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression.

The identification of EGR2 mutations in patients with neuropathies and the phenotype Egr2/Krox20(-/-) have demonstrated that the Egr2 transcription factor is critical for peripheral nerve myelination. However, the mechanism by which these mutations cause disease remains unclear, as most patients present with disease in the heterozygous state, whereas Egr2(+/-) mice are phenotypically normal. To understand the effect of aberrant Egr2 activity on Schwann cell gene expression, we performed microarray expression profiling to identify genes regulated by Egr2 in Schwann cells. These include genes encoding myelin proteins and enzymes required for synthesis of normal myelin lipids. Using these newly identified targets, we have shown that neuropathy-associated EGR2 mutants dominant-negatively inhibit wild-type Egr2-mediated expression of essential myelin genes to levels sufficiently low to result in the abnormal myelination observed in these patients.

Animals↗
PubMed2000

Functional compensation by Egr4 in Egr1-dependent luteinizing hormone regulation and Leydig cell steroidogenesis.

The Egr family of zinc finger transcription factors, whose members are encoded by Egr1 (NGFI-A), Egr2 (Krox20), Egr3, and Egr4 (NGFI-C) regulate critical genetic programs involved in cellular growth, differentiation, and function. Egr1 regulates luteinizing hormone beta subunit (LHbeta) gene expression in the pituitary gland. Due to decreased levels of LHbeta, female Egr1-deficient mice are anovulatory, have low levels of progesterone, and are infertile. By contrast, male mutant mice show no identifiable defects in spermatogenesis, testosterone synthesis, or fertility. Here, we have shown that serum LH levels in male Egr1-deficient mice are adequate for maintenance of Leydig cell steroidogenesis and fertility because of partial functional redundancy with the closely related transcription factor Egr4. Egr4-Egr1 double mutant male mice had low steady-state levels of serum LH, physiologically low serum levels of testosterone, and atrophy of androgen-dependent organs that were not present in either Egr1- or Egr4-deficient males. In double mutant male mice, atrophic androgen-dependent organs and Leydig cell steroidogenesis were fully restored by administration of exogenous testosterone or human chorionic gonadotropin (an LH receptor agonist), respectively. Moreover, a normal distribution of gonadotropin-releasing hormone-containing neurons and normal innervation of the median eminence in the hypothalamus, as well as decreased levels of LH gene expression in Egr4-Egr1-relative to Egr1-deficient male mice, indicates a defect of LH regulation in pituitary gonadotropes. These results elucidate a novel level of redundancy between Egr4 and Egr1 in regulating LH production in male mice.

Animals↗
PubMed1999

Preparation and activity of some novel organo-metallic complexes against Helicobacter pylori.

Some novel organo-metallic complexes were prepared by complexing the antibiotics erythromycin (CAS 114-07-8), doxycycline (CAS 564-25-0), ciprofloxacin (CAS 85721-33-1) and amoxicillin (CAS 26787-78-0) with bismuth citrate and their antibacterial activity against Helicobacter pylori and other micro-organisms were investigated. Amoxicillin-bismuth citrate had the strongest activity against H. pylori with a lowest minimum inhibitory concentration of 0.007 mg/l. The complexes exhibited moderate activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Bacillus subtilis. The findings suggest that the activity of these organo-metallic complexes might be specifically directed against H. pylori.

Anti-Bacterial Agents↗
PubMed1999

Infertility associated with incomplete spermatogenic arrest and oligozoospermia in Egr4-deficient mice.

Male fertility is complex and depends upon endocrine/paracrine regulatory mechanisms and morphogenetic processes occurring during testicular development, spermatogenesis (mitosis and meiosis) and spermiogenesis (spermatid maturation). Egr4 (NGFI-C, pAT133), a member of the Egr family of zinc-finger transcription factors, is thought to be involved in cellular growth and differentiation, but its specific function has been previously unknown. We derived Egr4 null mice through targeted mutagenesis and found that they were phenotypically normal with the exception that males, but not females, were infertile. Egr4 is expressed at low levels within male germ cells during meiosis and is critical for germ cell maturation during the early-mid pachytene stage. While most Egr4 null male germ cells undergo apoptosis during early-mid pachytene, some are capable of maturing beyond an apparent Egr4-dependent developmental restriction point. Consequently, a limited degree of spermiogenesis occurs but this is accompanied by markedly abnormal spermatozoon morphology and severe oligozoospermia. Egr4 appears to regulate critical genes involved in early stages of meiosis and has a singularly important role in male murine fertility. These data raise the possibility that Egr4 may contribute to some forms of human idiopathic male infertility.

Animals↗
PubMed1999

Optic disc size in ocular hypertension.

PURPOSE: To study the optic disc size in eyes with ocular hypertension (OHT) in comparison to primary open-angle glaucoma (POAG) and normals. METHODS: Optic disc photographs obtained with the Nidek 3dx NM camera were digitized (Nikon coolscan) and disc area calculated using Littmann correction in a randomly chosen eye of 28 OHT, 42 POAG and 30 normal subjects. OHT was defined as increased intraocular pressure with no disc or field changes suggestive of glaucoma with open angles. RESULTS: The optic disc area in OHT was 9.47 +/- 1.09 mm2; 12.27 +/- 2.87 mm2 in POAG; and 12.11 +/- 2.83 mm2 in normal individuals. CONCLUSION: Using magnification corrected morphometry and the criteria for OHT diagnosis, the optic disc area in OHT was significantly smaller (p < 0.0001) in POAG and normals.

Glaucoma, Open-Angle↗
PubMed1998

Biconical Bob Oscillatory Interfacial Rheometer.

This paper describes a biconical bob oscillatory interfacial rheometer designed to measure the dynamic viscoelastic response of a liquid-liquid interface subjected to a small amplitude oscillatory shear stress. This instrument is used to examine the rheological behavior of interfaces in the presence of surfactants, especially macromolecular types. Rheological parameters are calculated from a hydrodynamic analysis incorporating a linear viscoelastic interfacial rheological model. The general response of this instrument is compared with the oscillatory deep channel interfacial rheometer which is also capable of similar measurements. Measurements of interfacial viscoelasticity for the same liquid-liquid system with the two rheometers, the biconical bob and the deep channel rheometers, are shown to be comparable. This study demonstrates the intrinsic nature and, therefore, the instrument independence of these dynamic interfacial rheological properties. Accurate measurements of interfacial shear viscoelasticity can be carried out over a wide range of systems by combining measurements with the oscillatory interfacial rheometers. The limitations and regime of usefulness of these instruments are discussed. Copyright 1998 Academic Press.

Journal Article↗
PubMed1996

Comparison of Solubilization of Hydrocarbons in (PEO-PPO) Diblock versus (PEO-PPO-PEO) Triblock Copolymer Micelles

The solubilization of hydrocarbons by micelles formed of diblock and symmetric triblock copolymers in water are compared in the framework of a mean-field theory of solubilization. The block copolymers contain poly(ethylene oxide) as the hydrophilic block and poly(propylene oxide) as the hydrophobic block and are designated as EXPYEX or EWPZ (where E and P denote ethylene and propylene oxides and the subscripts denote the number of segments). In the presence of a variety of aromatic and aliphatic hydrocarbon solubilizates, the core radius, corona thickness, and aggregation number of the micelle and also the volume fraction of the hydrocarbon solubilized in the core are predicted. The calculations show that for identical molecular weights and block compositions, the diblock (E200P64) copolymer micelles have a much larger core radius, corona thickness, aggregation number, and volume fraction of the hydrocarbon solubilized in the core compared with the symmetric triblock (E100P64E100) copolymer micelles. In contrast, the diblock copolymer (E100P32), having the same block composition but half the molecular weight of the symmetric triblock copolymer (E100P64E100), gives rise to micelles having the same core radius, corona thickness, and volume fraction of the hydrocarbon solubilized as the micelles formed of the triblock copolymer, and an aggregation number twice that of the triblock copolymer micelle.

Journal Article↗
PubMed1996

A novel catecholamine, arbutamine, for a pharmacological cardiac stress agent.

Arbutamine, developed for use as a cardiac stress agent, was compared with isoproterenol and dobutamine in anesthetized dogs for cardiovascular actions prior to and after beta-adrenergic blockade with propranolol. The efficacy and safety of arbutamine were also evaluated in a canine model of myocardial ischemia obtained by partially occluding the left anterior descending coronary artery. Comparison of hemodynamic variables in normal dogs showed that arbutamine was approximately equipotent to isoproterenol in increasing heart rate and cardiac contractility, and in decreasing total peripheral vascular resistance and mean arterial blood pressure. Arbutamine was 210 times more potent than dobutamine in increasing cardiac contractility by 70%; however, at this dose dobutamine exhibited a negative chronotropic response. Beta-adrenergic blockade with propranolol shifted the agonist's dose-response curves for heart rate and contractility to the right; however, low doses of dobutamine exhibited a negative chronotropic effect and increased the total peripheral vascular resistance. In dogs subjected to partial left anterior descending coronary artery occlusion, arbutamine produced significant ST-segment deflections, beginning at a dose of 0.1 nmol/kg/min. Impairment of segment shortening, reflecting cardiac wall motion abnormality, was evident at a dose of 0.3 nmol/kg/min. Isoproterenol did not cause significant changes in these parameters. These results show that arbutamine is capable of producing graded increments in cardiac contractility and rate before and after beta-adrenergic blockage in normal dogs. In dogs subjected to coronary artery occlusion, it is capable of provoking myocardial ischemia at dose levels devoid of toxicity.

Animals↗
PubMed1996

Characterization of the adrenergic activity of arbutamine, a novel agent for pharmacological stress testing.

In this study, we characterized the interactions of arbutamine, a novel catecholamine developed for use as a cardiac stress testing agent, with different adrenergic receptor subtypes in vitro. These effects were compared with those of isoproterenol. In the electrically stimulated left atria of rats, arbutamine increased contractile force. The pD2 values (- log of the dose that produces 50% of the maximal responses) for arbutamine and isoproterenol were 8.45 +/- 0.15 and 8.55 +/- 0.02, respectively. Metoprolol shifted the concentration-effect curves for both isoproterenol and arbutamine to the right with a pA2 value (- log of the dose of the antagonist that reduces the maximal responses of an agonist to 50%) of 7.22-7.5. Both arbutamine and isoproterenol increased the rate of spontaneously beating rat right atria with pD2 values of 9.0 +/- 0.19 and 8.82 +/- 0.18, respectively. The affinity constants (KA) of arbutamine and isoproterenol for cardiac beta1-adrenergic receptors, as determined by competition binding assays, were found to be 7.32 and 6.04, respectively. In guinea pig trachea, arbutamine and isoproterenol produced a concentration-dependent relaxation that was blocked by propranolol. Their pD2 values were 7.9 +/- 0.1 and 8.2 +/- 0.1, respectively. Arbutamine contracted isolated rat aortic rings with a maximal increase of 38.1 +/- 6.7% that of 10 microM of norepinephrine. In rat white adipocytes, arbutamine, isoproterenol, and BRL-37344 stimulated glycerol release, with the order of potency being BRL-37344 > arbutamine > isoproterenol. In hamster brown adipocytes, the order was arbutamine > isoproterenol > BRL-37344. Moreover, arbutamine stimulated beta3-adrenergic receptors in guinea pig ileum. In conclusion, arbutamine is a novel catecholamine with similar potency and efficacy to that of isoproterenol. It stimulates cardiac beta1-, tracheal beta2-, and adiopocyte beta3-adrenergic receptors. Arbutamine does not stimulate alpha-adrenergic receptors at concentrations that were high enough to maximally activate the beta-adrenergic receptors.

Adipocytes↗