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Biomedical subjects

S Jain

Publications and source records attributed to S Jain.

At least 343 records · Page 19Linked to original sources

Isolated right ventricular hypertrophic obstructive cardiomyopathy.

Two cases of isolated hypertrophic cardiomyopathy of right ventricle without any involvement of interventricular septum or left ventricle are reported. Two cases reported in literature are also reviewed. In these cases symptoms are those of left ventricular hypertrophic obstructive cardiomyopathy. Right ventricular dominance on clinical examination and electrocardiogram and inspiratory increase in intensity of murmur are helpful clues. 2-Dimensional echocardiography with Doppler evaluation can confirm the diagnosis noninvasively.

Adult↗

Lack of morphine and enkephalin tolerance in 129/SvEv mice: evidence for a NMDA receptor defect.

In contrast to the rapid development of tolerance to morphine in CD-1 mice, tolerance is not seen in 129/SvEv mice implanted with morphine pellets or given daily morphine injections for 5 days. Similarly, the progressive and complete loss of analgesia in CD-1 mice seen with repeated dosing of the delta ligand [D-Pen2, D-Pen5]enkephalin is not observed in 129/SvEv mice. In contrast, tolerance develops normally to both the kappa1 drug U50,488H and the kappa3 agent naloxone benzoylhdrazone. N-methyl-D-aspartate (NMDA) given alone attenuates morphine analgesia in CD-1 mice and accelerates the development of tolerance in CD-1 mice when given daily with morphine. In contrast, NMDA has no significant effect in the 129/SvEv mice in either paradigm. Activation of NMDA receptors can lead to the production of nitric oxide, which also is involved with morphine tolerance. Sodium nitroprusside and L-arginine increase nitric oxide levels and decrease morphine analgesia in both the control CD-1 and 129/SvEv mice. Thus, the defect in the NMDA/nitric oxide cascade responsible for the loss of morphine tolerance in the 129/SvEv mice rests at the level of the NMDA receptor itself or in the steps up to the activation of nitric oxide synthase.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Knowledge, attitudes and practice of epilepsy: experience at a comprehensive rural health services project.

Beliefs regarding cause and preference of the treatment modality are important factors influencing any epilepsy programme. Patients own attitudes towards the on-going treatment are equally important in ensuring success of any such programme. The study involved interviews of 80 patients with epilepsy attending a comprehensive rural health services project, and was conducted according to a structured questionnaire. The majority of the patients were well informed regarding the cause of epilepsy, but more than half had tried alternative treatment methods. Many patients had misconceptions regarding the goal of the treatment and the consequences of missing a prescribed drug dose. Surprisingly few patients avoided taking medicines on days of religious fast. It was also noted that most patients depended on free medical supplies from the clinic dispensary, and a small number of patients would stop the medicines if these were not given free of cost. We stress the need to understand patients' concepts about the cause and the treatment of epilepsy, the need to educate them and their families regarding principles of modern medical treatment of epilepsy and most importantly, the need to maintain a regular, uninterrupted supply of free medicines, to improve the effectiveness of similar epilepsy management programmes in the setting of rural India and other developing countries.

Adaptation, Psychological↗

Preventive health services and access to care for male veterans compared with their spouses.

The Veterans Health Administration is exploring ways to reform the current Veterans Affairs (VA) system in accordance with the changing health care environment of managed care. One proposal is for the VA to enlarge its patient base by expanding eligibility to include spouses of veterans. To compare reported preventive health care services received by male veterans and their spouses and to measure whether spouses would choose to receive their medical care through a VA medical center, we randomly selected 230 married male veterans and mailed self-administered questionnaires to be completed by them and their spouses; 170 (74%) eligible subjects completed the questionnaire. The mean age of the veterans and spouses was 73.6 and 67.4 years, respectively. Veterans reported significantly higher rates of receipt of recommended preventive services than their spouses in all 5 areas assessed, including blood pressure measurement; influenza, pneumococcal, and tetanus vaccinations; and serum cholesterol measurement. Veterans were significantly more satisfied than their spouses with their current health care. Finally, 83% (95% confidence interval, 77% to 89%) of spouses reported that they would choose to receive their medical care at the VA medical center is allowed to do so. These findings suggest that spouses of male veterans represent a sizable group that could be incorporated in the VA system, especially given their strong desire to do so.

Aged↗

Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor.

In an attempt to identify cofactors that could possibly influence the transcriptional activity of peroxisome proliferator-activated receptors (PPARs), we used a yeast two-hybrid system with Gal4-PPARgamma as bait to screen a mouse liver cDNA library and have identified steroid receptor coactivator-1 (SRC-1) as a PPAR transcriptional coactivator. We now report the isolation of a cDNA encoding a 165-kDa PPARgamma-binding protein, designated PBP which also serves as a coactivator. PBP also binds to PPARalpha, RARalpha, RXR, and TRbeta1, and this binding is increased in the presence of specific ligands. Deletion of the last 12 amino acids from the carboxyl terminus of PPARgamma results in the abolition of interaction between PBP and PPARgamma. PBP modestly increased the transcriptional activity of PPARgamma, and a truncated form of PBP (amino acids 487-735) acted as a dominant-negative repressor, suggesting that PBP is a genuine coactivator for PPAR. In addition, PBP contains two LXXLL signature motifs considered necessary and sufficient for the binding of several coactivators to nuclear receptors. In situ hybridization and Northern analysis showed that PBP is expressed in many tissues of adult mice, including the germinal epithelium of testis, where it appeared most abundant, and during ontogeny, suggesting a possible role for this cofactor in cellular proliferation and differentiation.

Amino Acid Sequence↗

Functionally differentiating two neuronal nitric oxide synthase isoforms through antisense mapping: evidence for opposing NO actions on morphine analgesia and tolerance.

Several isoforms of neuronal nitric oxide synthase (nNOS) have been identified. Antisense approaches have been developed which can selectively down-regulate nNOS-1, which corresponds to the full-length nNOS originally cloned from the brain, and nNOS-2, a truncated form lacking two exons which is generated by alternative splicing, as demonstrated by decreases in mRNA levels. Antisense treatment also lowers nNOS enzymatic activity. Down-regulation of nNOS-1 prevents the development of morphine tolerance. Whereas morphine analgesia is lost in control and mismatch-treated mice given daily morphine injections for 5 days, mice treated with antisense probes targeting nNOS-1 show no decrease in their morphine sensitivity over the same time period. Conversely, an antisense probe selectively targeting nNOS-2 blocks morphine analgesia, shifting the morphine dose-response curve over 2-fold to the right. Both systems are active at the spinal and the supraspinal levels. An antisense targeting inducible NOS is inactive. Studies with NG-nitro-L-arginine, which does not distinguish among NOS isoforms, indicate that the facilitating nNOS-2 system predominates at the spinal level while the inhibitory nNOS-1 system is the major supraspinal nNOS system. Thus, antisense mapping distinguishes at the functional level two isoforms of nNOS with opposing actions on morphine actions. The ability to selectively down-regulate splice variants opens many areas in the study of nNOS and other proteins.

Analgesia↗

Construction of shuttle vectors for genetic manipulation and molecular analysis of mycobacteria.

Two novel shuttle vectors for mycobacteria are described which have been derived from the expression system pSD5 developed in our laboratory. Plasmid pSD5B is a promoter-selection vector containing a promoterless lacZ gene and allows the identification of mycobacterial promoters by the blue colour of the colonies on solid media containing XGal. Moreover, the chronological order of appearance of blue colonies and intensity of colour provide a qualitative index of transcriptional strengths of the cloned promoters. Plasmid pSD5C has been designed to construct mycobacterial genomic libraries and express the cloned DNA inserts as fusion proteins with maltose binding protein in mycobacteria. Libraries in pSD5C provide feasibility for their screening with either DNA probes or specific antisera for identifying the genes of interest and for isolation of specific genetic loci by complementation of Escherichia coli and mycobacterial mutants. These vectors combine the ease of working in E. coli with the advantage of directly propagating them in mycobacteria without further manipulations. Finally, we demonstrate that these vectors function efficiently both in fast growing Mycobacterium smegmatis and slow growing mycobacteria including Mycobacterium tuberculosis and Mycobacterium bovis BCG.

BCG Vaccine↗

A Theoretical Study on Gas-Phase Coating of Aerosol Particles

In situ coating of aerosol particles by gas-phase and surface reaction in a flow reactor is modeled accounting for scavenging (capture of small particles by large particles) and simultaneous surface reaction along with the finite sintering rate of the scavenged particles. A log-normal size distribution is assumed for the host and coating particles to describe coagulation and a monodisperse size distribution is used for the coating particles to describe sintering. As an example, coating of titania particles with silica in a continuous flow hot-wall reactor was modeled. High temperatures, low reactant concentrations, and large host particle surface areas favored smoother coatings in the parameter range: temperature 1700-1800 K, host particle number concentration 1 x 10(5)-1 x 10(7) #/cm3, average host particle size 1 &mgr;m, inlet coating reactant concentration (SiCl4) 2 x 10(-7)-2 x 10(-10) mol/cm3, and various surface reaction rates. The fraction of silica deposited on the TiO2 particles decreased by more than seven times with a hundredfold increase in SiCl4 inlet concentration because of the resulted increase in the average SiO2 particle size under the assumed coating conditions. Increasing the TiO2 particle number concentration resulted in higher scavenging efficiency of SiO2. In the TiO2/SiO2 system it is likely that surface reaction as well as scavenging play important roles in the coating process. The results agree qualitatively with experimental observations of TiO2 particles coated in situ with silica.

Journal Article↗

Blockade of morphine-induced hindlimb myoclonic seizures in mice by ketamine.

Morphine administration can lead to a variety of side-effects, including myoclonus. In an animal model, high morphine doses given intrathecally elicit hindlimb myoclonic seizures which are not influenced by traditional opioid receptor antagonists, such as naloxone. Ketamine prevents this seizure-like activity in a dose-dependent manner. The response is stereoselective, with S-ketamine far more potent than R-ketamine. A competitive NMDA antagonist, NPC17742, also prevents the seizures, although less potently than ketamine. Dextromethorphan has limited activity in this model, while haloperidol and pentothal are without any effect.

Amino Acids↗

Dilute topical proparacaine for pain relief after photorefractive keratectomy.

PURPOSE: The purpose of the study is to determine whether there is a nonanesthetic and nontoxic concentration of topical proparacaine that can be applied repeatedly to the cornea to reduce pain after photorefractive keratectomy (PRK). METHODS: Part I: To determine a nonanesthetic concentration, the corneal sensitivity of 50 healthy volunteers was assessed using aesthesiometry before and after a drop of either 0.01%, 0.025%, 0.05%, 0.1%, or 0.2% topical proparacaine. Ten volunteers similarly were tested with multiple doses of 0.05% proparacaine. To evaluate toxicity, ten healthy volunteers self-administered 0.05% proparacaine to one eye and placebo to the other eye every 15 minutes for 12 hours on day 1 and every hour for 12 hours on days 2 through 7. Subjects were assessed throughout the week using visual acuity, slitlamp examination, aesthesiometry, and ultrasonic pachometry. Part II: In a prospective, double-masked study, 34 patients who underwent PRK (48 eyes) self-administered either topical 0.05% proparacaine or placebo for 1 week after PRK as needed to reduce pain. Patients recorded their pain score before and after drop use and answered a pain-relief questionnaire. RESULTS: Part I: Proparacaine concentrations greater than or equal to 0.1% eliminated sensation from some corneas; concentrations of less than or equal to 0.05% were never fully anesthetic. No corneal toxicity was observed except for some minimal punctate staining in both treatment and placebo eyes. Part II: Patients in the treatment group had significantly more pain relief (P < 0.001) for a longer period (P < 0.001) than did patients in the control group. Average change in pain score was significantly greater in the treatment group (P < 0.002). No significant difference in the number of days needed to reach complete epithelial healing was found between the two groups (P < 0.18). CONCLUSIONS: Dilute (0.05%) topical proparacaine is nonanesthetic and nontoxic, and can be used safely for at least 1 week to reduce pain after PRK.

Administration, Topical↗