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Biomedical subjects

S Jain

Publications and source records attributed to S Jain.

At least 379 records · Page 21Linked to original sources
PubMed1997

Molecular characterization of the murine Hif-1 alpha locus.

Hypoxia inducible factor 1 alpha (HIF-1 alpha) is a basic helix-loop-helix-PAS (bHLH-PAS) transcription factor that mediates certain cellular responses to low oxygen tension, iron chelators, Co2+, Ni2+, Mg2+, and low intracellular glucose concentration. Upon exposure to the above conditions, HIF-1 alpha is upregulated and heterodimerizes with the Ah receptor nuclear translocator (ARNT, also known as HIF-1 beta), the heterodimeric complex binds TACGTG-containing genomic enhancer elements, and activates transcription of target genes. As a first step in developing genetic models to study the biology related to cellular hypoxia, we have cloned the murine HIF-1 alpha cDNA, determined the tissue-specific expression of its mRNA, functionally analyzed its protein product, and characterized its promoter and its genomic structure. A comparison between the murine and human HIF-1 alpha protein sequence reveals 95%, 99%, and 83% identity in the bHLH, PAS, and variable domains, respectively. RNAse protection assays demonstrate that in adult mice, the mHIF-1 alpha mRNA is expressed at high levels in kidney, heart, brain, thymus, and placenta, with moderate expression in liver, spleen, testis, and lung and much lower expression in skeletal muscle testis. Northern blot analysis indicates that the mRNA of the murine HIF-1 alpha is transcribed in two forms, a major 4-kb species and a minor 5-kb species; both are present in all tissues examined. The Hif-1 alpha promoter is GC rich, does not have a TATA element near its transcriptional start site, and does not respond to hypoxia or Co2+. The mHIF-1 alpha structural gene is composed of 15 exons. The splice junction sites within the bHLH and the PAS domains of HIF-1 alpha gene are highly conserved with respect to a number of previously characterized members of the bHLH-PAS superfamily. However, unlike other bHLH-PAS genes, where the variable domain is encoded by 2 exons, the variable region of the mHIF-1 alpha gene is encoded by 7 exons. Furthermore, most of these splice junction sites in the variable region are conserved with that of HIF-2 alpha, a recently cloned hypoxia-responsive bHLH-PAS protein (also known as MOP2, EPAS1, and HLF). These data suggest that HIF-1 alpha, along with HIF-2 alpha, represents a new subclass of the bHLH-PAS superfamily.

Amino Acid Sequence↗
PubMed1997

Postoperative pain management.

Postoperative pain management is essential and must be approached as an integral part of the perioperative care. It should be systematic and based on sound physiologic and pharmacologic principles. The intra-operative management of pain is crucial, as there is perhaps an important role for preemptive analgesia. Because of its unique nature, pain is difficult to assess, but for good results adequate and repeated assessment are vital. The literature also points to the detrimental effects of inadequate pain control. There are a variety of methods available for pain management. In choosing a method, various factors need to be considered including physician skill, knowledge of analgesics and routes of administration, patient-related and clinical circumstances, the availability of an environment supportive of effective pain management, and the knowledge and skill of staff to assess and monitor patients. These need to be considered along with the risks and benefits and cost-benefit of the various drugs and techniques. The cornerstone of therapy is opioids, which can be administered by a variety of routes. The use of TEA with opioids and local anesthetics is highly beneficial, especially in high-risk patients. The aim should be to provide all patients a balanced analgesic regimen based on the identification of multiple mechanisms involved in postoperative pain.

Aged↗
PubMed1996

Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia and bipolar affective disorder.

A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close to the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tractlengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus.

Africa↗
PubMed1996

Peripheral kappa 1-opioid receptor-mediated analgesia in mice.

When injected directly into the tail, U50,488H is a potent analgesic in the tailflick assay (ED50 3.1 micrograms). The analgesic activity is lost if the radiant heat is focused 1 cm away from the site of injection. The kappa 1-opioid receptor antagonist nor-binaltorphimine given systemically reverses the local analgesic response of U50,488H, but the antagonist is 100-fold more potent when injected directly into the tail. Intrathecal antisense treatment with a probe targeting the mRNA encoding the kappa 1-opioid receptor blocks the local analgesic actions of U50,488H in the tail, suggesting that U50,488H is acting on dorsal ganglia neurons.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Analysis of thirteen trinucleotide repeat loci as candidate genes for schizophrenia and bipolar affective disorder.

A group of diseases are due to abnormal expansions of trinucleotide repeats. These diseases all affect the nervous system. In addition, they manifest the phenomenon of anticipation, in which the disease tends to present at an earlier age or with greater severity in successive generations. Many additional genes with trinucleotide repeats are believed to be expressed in the human brain. As anticipation has been reported in schizophrenia and bipolar affective disorder, we have examined allele distributions of 13 trinucleotide repeat-containing genes, many novel and all expressed in the brain, in genomic DNA from schizophrenic (n = 20-97) and bipolar affective disorder patients (23-30) and controls (n = 43-146). No evidence was obtained to implicate expanded alleles in these 13 genes as causal factors in these diseases.

Base Sequence↗
PubMed1996

Differential scanning calorimetric studies on the effect of ammonium and tetraalkylammonium halides on the stability of lysozyme.

The thermal denaturation of lysozyme was studied at pH 2.50 and 6.00 in aqueous solutions of ammonium (NH4Cl and NH4Br) and tetraalkylammonium halides (Me4NCl, Me4NBr, Et4NBr, Pr4NBr, Bu4NBr) using high-sensitivity differential scanning calorimetry. The transition temperature, heat capacity, enthalpy, entropy and free energy of denaturation have been determined by a least-squares fit of the excess heat capacity data to the two-state model. Ammonium and tetraalkylammonium halides (except Me4NCl and NH4Cl at high concentrations at pH 6.00) are found to destabilize lysozyme and the destabilization increases with increasing concentration and alkyl chain length. However, NH4Cl and Me4NCl act as stabilizers at high concentrations at pH 6.00. Results are discussed in terms of electrostatic and hydrophobic interactions. The stabilization of lysozyme by NH4Cl and Me4NCl can be attributed to the charge on the quaternary nitrogen atom while destabilization in tetraalkylammonium halides solution is due to the interaction between hydrophobic molecules of the medium and the hydrophobic parts of the protein.

Animals↗
PubMed1996

Modulation of opioid analgesia by agmatine.

Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, agmatine enhances morphine analgesia in a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater effect is observed when morphine is given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to the potentiation of morphine analgesia, agmatine (10 mg/kg) has no effect on morphine's inhibition of gastrointestinal transit. delta-Opioid receptor-mediated analgesia also is potentiated by agmatine, but kappa1-receptor-mediated (U50,488H; trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetemide) and kappa3-opioid receptor-mediated (naloxone benzoylhydrazone) analgesia is not significantly enhanced by any dose of agmatine tested in this acute model. In chronic studies, agmatine at a low dose (0.1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days. A higher agmatine dose (10 mg/kg) has a similar effect. Agmatine also blocks tolerance to the delta-opioid receptor ligand [D-Pen2,D-Pen5]enkephalin given intrathecally, but not to the kappa3-opioid receptor agonist naloxone benzoylhydrazone. Despite its inactivity on kappa1-opioid analgesia in the acute model, agmatine prevents kappa1-opioid receptor-mediated tolerance. These studies demonstrate the dramatic interactions between agmatine and opioid analgesia and tolerance.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Production, purification, and characterization of recombinant human hemoglobin rainier expressed in Saccharomyces cerevisiae.

Hemoglobin Rainier is a naturally occurring hemoglobin variant in which the beta 145 tyrosine is substituted with cysteine. The alpha and beta Rainier globin cDNAs were cloned in a high copy number vector and expressed in Saccharomyces cerevisiae under the control of galactose-regulated hybrid promoters. Using this system, we have expressed individual alpha and beta Rainier globin chains. Coexpression of both alpha and beta Rainier cDNAs resulted in the production of a functional hemoglobin molecule. Purification of the recombinant protein was accomplished by ion exchange chromatography. The N-termini of the alpha and beta chains were correctly processed, and the molecular mass, as determined by mass spectrometry, indicated amino acid composition identical to that of natural hemoglobin Rainier. The chromatographic properties of the recombinant hemoglobin Rainier were similar to human-derived hemoglobin A0. The purified recombinant hemoglobin molecule was shown to have an elevated oxygen affinity and a reduced cooperativity as previously reported for natural hemoglobin Rainier. Production of recombinant hemoglobin and especially hemoglobin variants like hemoglobin Rainier has the potential to facilitate use of hemoglobin as a blood substitute as well as in specific applications, such as for use as a therapeutic agent in the treatment of hypotension associated with septic shock.

Chromosome Mapping↗
PubMed1996

Morphometric analysis of the right gastroepiploic artery and the internal mammary artery.

BACKGROUND: The internal mammary artery (IMA) and the right gastroepiploic artery (RGEA) are frequently used as conduits for coronary artery bypass grafting. METHODS: Morphometric measurements and histologic characteristics of the RGEA and the IMA were studied in 25 patients undergoing coronary artery bypass grafting. RESULTS: External radius was found to be more in the IMA (range, 18 to 56 microns; mean, 39.56 microns) in comparison with the RGEA (range, 24 to 51 microns; mean, 32.52 microns; p < 0.01). There was no significant difference between the vessels in intimal thickness (IMA: 0.0 to 0.25 micron; mean, 0.05 micron; RGEA: 0.0 to 0.28 micron; mean, 0.09 micron), internal radius (IMA: 5 to 47 microns; mean, 28.40 microns; RGEA: 16 to 42 microns; mean, 23.56 microns), area of media (IMA: 1,690 to 3,476 microns2; mean, 2,777.52 microns2; RGEA: 1,659 to 3,600; mean, 3,012.44 microns2), intimal thickening index (IMA: 0.0 to 0.02; mean, 0.01; RGEA: 0.0 to 0.13; mean, 0.01), and medial index (IMA: 0.14 to 0.60; mean, 0.36; RGEA: 0.18 to 0.63; mean, 0.39). Histologic examination of the RGEA showed more defects in continuity of internal elastic lamina and rich smooth muscle cells in the media. CONCLUSIONS: There was no difference in the morphometric measurements of the IMA and the RGEA except external radius, which was greater for the IMA. The histologic differences found in the RGEA may indicate an increased propensity for atherosclerosis of the RGEA as compared with the IMA. Some concern regarding the long-term patency of the RGEA in myocardial revascularization is warranted.

Adult↗
PubMed1996

Cold swim stress leads to enhanced splenocyte responsiveness to concanavalin A, decreased serum testosterone, and increased serum corticosterone, glucose, and protein.

This study extends previous observations of the conditions under which enhancement of lymphocyte activity occurs following cold swim stress and presents a possible explanation for the enhancement observed. Eight- to twelve-week old male Sprague-Dawley rats swam for 10 minutes daily for one, three, or five days in cold water at 15 degrees C and were killed 0, 30, or 240 minutes following the last swim. Apparatus control animals were placed into an empty swim tank for 10 minutes and then returned to their home cages. Home cage control animals were not manipulated experimentally at all. Splenocyte but not thymocyte responses to concanavalim A were significantly enhanced after one, three, and five days of stress. This enhancement was seen after 0, 30, and 240 minutes of recovery and also in the apparatus controls! The number of splenocytes did not change significantly, but thymocyte number declined following the swims. The blood displayed no changes in leukocyte percents. Serum corticosterone levels were significantly higher and serum testosterone levels were significantly lower after one, three, and five days of stress. The drop in testosterone levels may have released the lymphocytes from inhibition by this hormone, resulting in increased responsiveness. There were significant elevations in levels of blood glucose and protein following one, three, and five days of stress sessions, correlated with the increases in serum corticosterone.

Animals↗
PubMed1996

Rehabilitation in limb deficiency. 2. The pediatric amputee.

This self-directed learning module highlights advances in the evaluation and management of the pediatric amputee. It is part of the chapter on rehabilitation in limb deficiency in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article discusses the etiology and terminology of childhood limb deficiency. Developmental milestones are used as a guide to prescribing prosthetic devices for children, and tables suggesting such guidelines are included. Specific clinical examples are provided to illustrate management issues. Advances that are covered include limb-sparing procedures in the management of lower extremity malignancy.

Adolescent↗
PubMed1996

Objective measurement of corneal light scattering after excimer laser keratectomy.

PURPOSE: To obtain objective measurements of corneal light scattering after excimer laser keratectomy, and to evaluate the relation of light scattering to clinical haze grading and visual acuity. METHODS: The authors measured best-corrected visual acuity, subjective clinical haze grade, and corneal light-scattering index in patients undergoing photorefractive keratectomy (PRK) (n=26), and phototherapeutic keratectomy (n=8), preoperatively and postoperatively at 1,3,6,9, and 12 months or later. Corneal light scattering was correlated with visual acuity and clinical haze grade. RESULTS: Corneal light scattering increased after PRK and was reduced after phototherapeutic keratectomy. Corneal light scattering index showed a stronger positive correlation with logMAR visual acuity (r=0.57) than clinical haze grading (r=0.34). Corneal light-scattering index (P<0.05 at 1 and 3 months) and clinical haze grading (P<0.05 at 6, 9, and 12 months) were significantly higher in eyes undergoing PRK with ablation depths of more than 80 microns. CONCLUSIONS: Excimer laser surgery affects corneal light scattering. Ablations with depths greater than 80 microns produce significantly higher levels of haze than those less than 80 microns. Objective measurement of corneal light scattering may be useful in monitoring the outcome of excimer keratectomy.

Cornea↗
PubMed1996

Direct role of HLA-B5 in influencing susceptibility to Takayasu aortoarteritis.

To investigate genetic factors involved in the pathogenesis of Takayasu arteritis (TA), North Indian patients belonging to the states of Punjab, Haryana, Uttar Pradesh and Delhi were examined for HLA-class I and class II antigens and the data compared with healthy controls from the same ethnic group. Additionally, DNA typing was performed using polymerase chain reaction/sequence specific oligonucleotide probe (PCR-SSOP) technique to evaluate the distribution of molecular alleles in the healthy Indian population as compared to orientals and Western caucasoids. The frequency of HLA-B5 was significantly increased in patients as compared to controls (chi 2 = 32.5, corrected P value, Pc = 3 x 10(-6), relative risk = 4.3). Serological splitting of B5 into B51 and B52 did not reveal an association with any of the two subtypes. Weak association was also noticed with DR8 in the patient group (chi 2 = 8.2, Pc = 0.05). Distribution of the molecular subtypes of various HLA-B and DR alleles indicated that although the Indian population is essentially caucasoid, it comprises of an admixture of both caucasoid as well as oriental alleles/haplotypes. The observations clearly suggest that (a) HLA-linked genes are involved in the development of Takayasu arteritis, and (b) rather than a subtype of B5, the whole molecule or its closely linked gene(s) influence susceptibility to TA.

Adolescent↗
PubMed1996

Current status of Takayasu arteritis in India.

The clinical features of 106 patients of Takayasu arteritis (TA) seen over a period of 16 years are documented (65 females and 41 males). The mean age was 27.3 +/- 9.2 years. Hypertension was the commonest mode of presentation (51.3%) and was detected in 82 patients (77.4%) at the time of presentation. Vascular bruits were heard in 72 patients (67.9%) and 13 patients (12.3%) were in congestive heart failure. Aortography was performed in 95 patients. Based on the extent of involvement, Type I (branches of aortic arch) was seen in 7 (6.6%) patients, Type II (aortic arch, its branches and descending thoracic aorta) in 7 (6.6%) patients, Type III (descending thoracic aorta and abdominal aorta) in 4 (3.8%) patients, Type IV (abdominal aorta only) in 29 (27.3%) patients and Type V (aortic arch, descending thoracic aorta and abdominal aorta) in 59 (55.7%) patients. Therapeutic modalities included antihypertensive drug therapy in 81 patients, antitubercular drugs in 8 patients, steroids in 16 patients and cyclophosphamide in one patient. Response to steroids was satisfactory in 5 of these 16 patients while the lesions of vasculitis healed in the patient who was treated with cyclophosphamide. Surgical interventions included nephrectomy and autotransplantation of kidney in 3 patients each and revascularization in 4 patients and angioplasty in 4 patients. In the area of pathogenesis of this disease, a high activity of protein kinase C(PKC), an increased intracellular calcium and inositol 1,4,5 triphosphate in both unstimulated and stimulated T cells of TA was observed. These findings suggest an activation of PKC-calcium pathway in TA.

Adolescent↗