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Biomedical subjects

B Jain

Publications and source records attributed to B Jain.

15 recordsLinked to original sources

Hydrogen bonding properties of Coumarin 151, 500, and 35: the effect of substitution at the 7-amino position.

The steady-state spectral properties (absorption and emission) of three structurally similar Coumarin dyes, C151, C500, and C35 were investigated in 13 different solvents. A Kamlet-Taft (KT) analysis of the spectral peak frequencies reveals that, in addition to polarity, hydrogen bonding between the carbonyl oxygen and a protic solvent in the excited state imparts maximum stabilization for C151 and minimum for C35, while that for C500 lies in between. The spectral properties of the three dyes in two solvents, chloroform and THF, which have similar polarity in the KT scale but have only hydrogen-bond donor (chloroform) and hydrogen-bond acceptor (THF) properties, are seen to be sensitive to the substitution pattern at the 7-amino position. In addition, a slow emission spectral relaxation is observed for C151 and C500 having a time constant of approximately 500 ps in chloroform. For C35 this was too fast to be detected by the time resolution of our setup. The exact reason for this slow spectral relaxation in chloroform is unclear at present, and further studies are needed to understand clearly the structural effects on the hydrogen bonding dynamics of these dyes.

Chloroform↗

Statistics of Dark Matter Halos from Gravitational Lensing.

We present a new approach to measure the mass function of dark matter halos and to discriminate models with differing values of Omega through weak gravitational lensing. We measure the distribution of peaks from simulated lensing surveys and show that the lensing signal due to dark matter halos can be detected for a wide range of peak heights. Even when the signal-to-noise ratio is well below the limit for detection of individual halos, projected halo statistics can be constrained for halo masses spanning galactic to cluster halos. The use of peak statistics relies on an analytical model of the noise due to the intrinsic ellipticities of source galaxies. The noise model has been shown to accurately describe simulated data for a variety of input ellipticity distributions. We show that the measured peak distribution has distinct signatures of gravitational lensing, and its non-Gaussian shape can be used to distinguish models with different values of Omega. The use of peak statistics is complementary to the measurement of field statistics, such as the ellipticity correlation function, and is possibly not susceptible to the same systematic errors.

Journal Article↗

An oxaloacetate decarboxylase homologue protein influences the intracellular survival of Legionella pneumophila.

Legionella pneumophila is a facultative intracellular parasite which is able to survive in various eukaryotic cells. We characterised a Tn5-mutant of the L. pneumophila Corby strain and were able to identify the insertion site of the transposon. It is localised within an open reading frame which shows high homology to the alpha-subunit of the oxaloacetate decarboxylase (OadA) of Klebsiella pneumoniae. The OadA homologous protein of L. pneumophila was detected in the wild-type strain by Western blotting. Since the intracellular multiplication of the oadA- mutant strain is reduced in guinea pig alveolar macrophages and human monocytes, it is concluded that the oadA gene product has an effect on the intracellular survival of L. pneumophila.

Animals↗

A cyclophilin-like peptidyl-prolyl cis/trans isomerase from Legionella pneumophila--characterization, molecular cloning and overexpression.

Legionella pneumophila is the causative agent of a severe form of pneumonia in humans (Legionnaires' disease). A major virulence factor, the Mip protein (FK506-binding protein, FKBP25mem), belongs to the enzyme family of peptidyl-prolyl cis/trans isomerases (PPlases). Here we show that L. pneumophila Philadelphia I possesses an additional cytoplasmic PPlase at a level of enzyme activity comparable to that of FKBP25mem. The N-terminal amino acid sequence of the purified protein was obtained by Edman degradation and showed that the protein is a member of the cyclophilin family of PPlases. The Icy gene (Legionella cyclophilin) was cloned and sequenced. It encodes a putative 164-amino-acid protein with a molecular mass of 17968 Da called L. pneumophila cyclophilin 18 (L.p.Cyp18). Amino acid sequence comparison displays considerable similarity to the cytoplasmic and the periplasmic cyclophilins of Escherichia coli with 60.5% and 51.5% identity, respectively. The substrate specificity and inhibition by cyclosporin A revealed a pattern that is typically found for other bacterial cyclophilins. An L. pneumophila Cyp18 derivative with a 19-amino-acid polypeptide extension including a 6-histidine tag and an enterokinase cleavage site exhibits PPlase activity when produced at high levels in E. coli K-12. After removal of the extension by enterokinase, the properties of the recombinant Cyp18 were indistinguishable from those of the authentic enzyme. In order to investigate the influence of Cyp18 on intracellular survival of L. pneumophila an Icy-negative L. pneumophila strain was constructed. Compared with the wild-type strain, the mutant did not exhibit a significant phenotype but was 10-fold less invasive for Acanthamoeba castellanii. Like human cyclophilin, the L. p. Cyp18 exhibits nuclease activity, but this enzymatic activity does not appear to be linked with the native structure of the protein.

Amino Acid Isomerases↗

Study on in vitro stability of polymerized liposomes.

We studied the stability of liposomes composed of polymerized phospholipid, 1,2-bis-(octadeca-2,4-dienoyl)-sn-glycero-3-phosphocholine (DENPC), to pH changes and the presence of bile salts, monitoring the leakage of 3H-sucrose entrapped in liposomes. The stability of polymerized DENPC-liposomes to acidic media (pH 3.3 and 2), and the presence of bile salts (20 mM), was much higher than that of nonpolymerized DENPC-liposomes and liposomes composed of conventional phospholipids. The stability of polymerized DENPC-liposomes was increased in the presence of carboxymethyl chitin (CM-chitin).

Bile Acids and Salts↗

Cardiopulmonary function and autologous bone marrow transplantation: results and predictive value for respiratory failure and mortality. The University of Nebraska Medical Center Bone Marrow Transplantation Pulmonary Study Group.

Cardiopulmonary complications are a major cause of morbidity and mortality in patients undergoing high-dose therapy with stem cell transplant support. Since exercise tolerance testing (ETT) assesses the cardiopulmonary reserve of an individual, we hypothesized that ETT performed prior to transplant would predict respiratory failure and mortality and would be a superior predictor over resting cardiopulmonary function tests. We performed a retrospective study of 191 lymphoma patients who underwent ETT prior to transplant between 1 June 1990 and 31 December 1992 and compared the results of ETT with resting pulmonary function tests (PFT) and resting cardiac ejection fraction (EF). ETT revealed that cardiac, pulmonary and combined cardiopulmonary limitation were observed in 31, 20 and 16% of the patients, respectively, with a gas diffusion-type limitation being the most common exercise limitation. Resting PFT were abnormal in 58% of patients with a diffusion defect being the most common abnormality. Low EF was observed in 6.8% of patients. Twelve patients eventually required mechanical ventilation post-transplant with only the resting diffusion PFT predictive of this complication. There were five early deaths that were attributable to respiratory failure and neither resting nor ETT studies were predictive of these deaths. ETT and EF performed prior to transplant in lymphoma patients undergoing autologous transplant do not predict for either respiratory failure or short-term mortality. Our findings may be due to the rather low incidence of respiratory failure (6.3%) and low early mortality from cardiopulmonary complications (2.6%) seen in our patient population.

Adolescent↗

TNF-alpha and IL-1 beta upregulate nitric oxide-dependent ciliary motility in bovine airway epithelium.

Airway epithelial cells can be modulated by cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta that are released from inflammatory cells. Since ciliary motility is an important host defense function of airway epithelium, we hypothesized that cytokines, released from lung macrophages, upregulate ciliary motility. To test this hypothesis, ciliary beat frequency (CBF) was measured by video microscopy in cultured ciliated bovine bronchial epithelial cells (BBECs) incubated for 24 h with bovine alveolar macrophage-conditioned medium (AM-CM). Exposure to AM-CM resulted in a delayed (> or = 2 h) increase in CBF that was maximal after 24 h exposure (13.70 +/- 0.43 for AM-CM vs. 9.44 +/- 0.24 Hz for medium; P < 0.0001) and which was largely blocked by either anti-TNF-alpha or anti-IL-1 beta antibodies. rTNF-alpha or rIL-1 beta similarly increased CBF, which could be blocked by preincubation with either anti-rTNF-alpha or anti-rIL-1 beta antibodies. Preincubation of BBECs with actinomycin D or dexamethasone also blocked rTNF-alpha- and rIL-1 beta-induced cilia stimulation, suggesting that new protein synthesis is required for cytokine-induced upregulation of CBF. Since NO is known to upregulate ciliary motility and cytokines can induce NO synthase (NOS), we hypothesized that TNF-alpha and IL-1 beta increase CBF by inducing NOS in BBECs. The cilia stimulatory effects of TNF-alpha or IL-1 beta were inhibited by NG-monomethyl-L-arginine, a competitive NOS inhibitor, and restored by the addition of either L-arginine, an NOS substrate, or sodium nitroprusside, an NO donor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

An assessment of short-acting hypnotics.

Insomnia, the experience of poor quality or quantity of sleep, is a very common complaint. Approximately 65 million adults (36% of the American population) complain of poor sleep, and of this group, 25% have insomnia on a chronic basis. These chronic insomniacs not only report higher rates of difficulty with concentration, memory and the ability to cope with minor irritations but also have 2.5 times more fatigue-related automobile accidents than do good sleepers. Despite its ubiquity, insomnia is often either untreated or inadequately treated. Short-acting hypnotics are advocated for transient insomnia, which lasts less than 3 weeks, and in patients with chronic insomnia as an adjunctive treatment where nonpharmacological treatment is not sufficient to alleviate insomnia and the related daytime detrimental effects. The putative adverse effects of hypnotics must be weighted against the severe health effects caused by continued sleep impairment. If hypnotic agents are used, they should be taken nightly only for brief use, or intermittently in longer term use. Benzodiazepines, zolpidem and zopiclone (in countries where the latter is available) remain the recommended hypnotic agents, although in the past few years there has been much criticism in lay magazines and on television about the use of benzodiazepines. However, this review of the efficacy and tolerability data of the short-acting hypnotics suggests that triazolam is comparable with other short-acting hypnotics at equipotent doses while taking into consideration that for every hypnotic, different study populations display different degrees of efficacy. In addition, contrary to previous suggestions that such adverse effects are rebound insomnia and anterograde amnesia are unique to triazolam, hypnotically equivalent doses of tirazolam have not been shown to produce these effects more frequently than other short-acting hypnotics. The newer nonbenzodiazepine hypnotics seem to be equally efficacious as the short-acting benzodiazepines; whether they will truly have a better adverse effect profile will be determined as more clinical experience accumulates. Despite the availability, relative safety and efficacy of these newer hypnotic agents, they should not be perceived as the sole treatment for insomnia and should be used in conjunction with nonpharmacological techniques (such as adherence to good sleep hygiene, sleep restriction, stimulus control and biofeedback therapy).

Adult↗

Modulation of airway epithelial cell ciliary beat frequency by nitric oxide.

NOS activity has been recently described in airway epithelial cells. Because these cells are often ciliated we hypothesized that NO modulates airway ciliary beating. CBF was measured in cultured BBECs using video microscopy. L-NMMA, a NOS inhibitor, caused a 40% decrease in CBF following pre-stimulation with isoproterenol (8.5 +/- 0.3 Hz vs 14.6 +/- 0.2 Hz; p < 0.0001) which lasted approximately 60 minutes. Similar attenuation in CBF after isoproterenol pre-treatment was observed with another NOS inhibitor, L-NAME. NOS inhibitor-induced CBF slowing was also observed when cells were pre-stimulated with either bradykinin or substance P and was completely reversed by L-arginine or SNP but not by D-arginine. These observations demonstrate a novel NO-dependent mechanism that upregulates ciliary motility in response to stimulation.

Amino Acid Oxidoreductases↗

A simple, modified technique for direct chromosome preparation from chorionic villi.

Chorionic villus sampling (CVS) has proved to be an elegant and safe technique for prenatal diagnosis of genetic diseases during the first trimester of pregnancy. Despite a number of obvious advantages, the wide application of direct cytogenetic analysis of CVS has been hampered by serious technical problems involving large numbers of incomplete metaphases and poor chromosome morphology. A chromosome preparation technique direct from CVS has been devised which involves modifications in the hypotonic and dissociation stages. It yielded satisfactory results in fifteen samples within 24 h of sampling. It is suggested that this simple, modified technique can provide complete chromosomal analysis within a short time for prenatal diagnosis of genetic diseases, and may be used as a routine method in cytogenetic laboratories.

Adult↗

Ampicillin tolerance of Legionella pneumophila for counter-selection of transconjugants in heterospecific matings with Escherichia coli donors.

Legionella pneumophila, the causative agent of Legionnaires' disease is sensitive to ampicillin. However, the slowly growing bacteria are not killed even by high doses of this antibiotic. This natural tolerance was used for counter-selection of trans-conjugants in heterospecific matings with Escherichia coli as donor. This approach is useful for gentic manipulations in Legionella, as it avoids the use of antibiotic-resistant variants, which have to be tested for full virulence before use.

Ampicillin↗

Crossed renal ectopia with pelvic lipomatosis: a new syndrome involving chromosome 1.

An 18-year-old male patient is described who possesses both kidneys on one side (crossed renal ectopia), together with pelvic lipomatosis. In general, lipomatosis is benign, but here the tissue shows the rare feature of malignancy. Chromosomally, the patient is typically characterised by somatic translocations involving chromosome 1 (37% metaphases); these almost always exhibit a whole chromosome translocation with chromosome 6 (35%), although involvement of chromosome 1 with chromosome 8 is present in 2% of metaphases. Other chromosomal features encountered in Giemsa-stained and G-banded preparations from lymphocyte cultures include the prevalence of a small Y chromosome in 25% of metaphases, the presence of marker dots in 20%, and acrocentric associations in 8%-10% of metaphases. However, more than 50% of metaphases have a normal 46XY karyotype with a normal-sized Y-chromosome. Crossed renal ectopia with pelvic lipomatosis can therefore be assigned to a new syndrome characterised by a whole-chromosome translocation involving chromosomes 1 and 6.

Adolescent↗