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Biomedical subjects

J Shah

Publications and source records attributed to J Shah.

At least 199 records · Page 11Linked to original sources
PubMed1991

Effect of cadmium on Ca2+ transport in brain microsomes.

The effect of Cd2+ on Ca2+ transport properties (uptake/release) in rat brain microsomes is examined by the tracer method using 45Ca2+. Cadmium ion (Cd2+) shows a dose-dependent inhibition of Ca(2+)-ATPase activity and consequently, exhibits a reduction in ATP-dependent Ca2+ uptake. In addition to this, Cd2+ also stimulates a rapid release of Ca2+ (t1/2 = 0.5 min) from the microsomes in a dose-dependent manner. The effect of Cd2+ is reversible by 1 mM cysteine or dithiothreitol (DTT). It is suggested that Cd2+ plays an important role in regulating the transmembrane flux of the cations in the microsomes. This effect is dramatically modulated by DTT suggesting a role of sulfhydryl groups in Ca(2+)-transport.

Animals↗
PubMed1991

Synthesis and expression of genes encoding tuna, pigeon, and horse cytochromes c in the yeast Saccharomyces cerevisiae.

Genes encoding tuna, pigeon, and horse cytochromes c were constructed with synthetic oligodeoxyribonucleotides having preferred codons and portions of the iso-1-cytochrome c-encoding gene from the yeast Saccharomyces cerevisiae. The genes were ligated into an expression vector, which contains the normal 5'- and 3'-untranslated regions of the yeast iso-1-cytochrome c gene, and were integrated in single copy into the chromosome. Yeast strains were also constructed with multiple integrated copies of the pigeon gene. The heterologous and normal mRNA levels of the single-copy strains were equivalent. Although the N-terminal methionines were completely cleaved in the heterospecific proteins, the levels of trimethylation of Lys72 and acetylation of N-terminal glycines ranged from 39-78% and 10-70%, respectively. Horse cytochrome c was produced at a nearly normal level, whereas the pigeon and tuna cytochromes c were produced at approx. 40% of the normal levels. The levels of the cytochromes c and growth of the mutant yeast strains indicated that the heterospecific cytochromes c had approx. 50% specific activity in vivo.

Acetylation↗
PubMed1991

Polymerase chain reaction-mediated gene synthesis: synthesis of a gene coding for isozyme c of horseradish peroxidase.

The synthesis of a gene coding for horseradish peroxidase (HRP, isozyme c; EC 1.11.1.7) is described using a polymerase chain reaction (PCR)-mediated gene synthesis approach developed in our laboratory. In this approach, all the oligonucleotides making up the gene are ligated in a single step by using the two outer oligonucleotides as PCR primers and the crude ligation mixture as the target. The PCR facilitates synthesis and purification of the gene simultaneously. The gene for HRP was synthesized by ligating all 40 oligonucleotides in a single step followed by PCR amplification. The gene was also synthesized from its fragments by using an overlap extension method similar to the procedure as described [Horton, R. M., Hunt, H. D., Ho, S. N., Pullen, J. K. & Pease, L. R. (1989) Gene 77, 61-68]. A method for combining different DNA fragments, in-frame, by using the PCR was also developed and used to synthesize the HRP gene from its gene fragments. This method is applicable to the synthesis of even larger genes and to combine any DNA fragments in-frame. After the synthesis, preliminary characterization of the HRP gene was also carried out by the PCR to confirm the arrangement of oligonucleotides in the gene. This was done by carrying out the PCR with several sets of primers along the gene and comparing the product sizes with the expected sizes. The gene and the fragments generated by PCR were cloned in Escherichia coli and the sequence was confirmed by manual and automated DNA sequencing.

Base Sequence↗
PubMed1991

A dose-ranging study of the pharmacokinetics of codeine phosphate following intravenous administration to rats.

The linearity of the pharmacokinetics of codeine was examined in male Sprague-Dawley rats given iv bolus doses of 1, 1.5, 3, and 4 mg/kg of codeine phosphate. Codeine and morphine were determined in serial blood samples utilizing HPLC with electrochemical detection. Codeine exhibits characteristics consistent with a two-compartment pharmacokinetic model. The kinetics of codeine are linear in the iv dose range 1-4 mg/kg. The ratio AUCmorphine:AUCcodeine increases disproportionately with increasing doses of codeine.

Animals↗
PubMed1991

Role of Na+,K(+)-ATPase in the centrally mediated hypotensive effects of potassium in anaesthetized rats.

Several investigators have demonstrated the antihypertensive properties of potassium in various models of hypertension. The present studies were conducted to determine whether central mechanisms contribute to these salutary effects of potassium. In Inactin-anaesthetized rats, intracerebroventricular administration of KCl solutions (0.375, 0.75 and 1.25 mumol/5 microliters) produced concentration-dependent reductions in arterial pressure and heart rate. These effects were significantly attenuated by prior central administration of ouabain, a selective inhibitor of the sodium pump. In a separate series of experiments, prior central administration of alpha 1- and alpha 2-antagonist phentolamine, or the dopamine receptor (DA1 and DA2) antagonist RS-sulpiride, was also effective in inhibiting the hypotensive and bradycardiac effects of intracerebroventricular administration of potassium. Thus, these data suggest that activation of Na+,K(+)-ATPase and central noradrenergic and dopaminergic mechanisms are involved in the central actions of potassium and these central mechanisms may contribute to the salutary effects of a potassium-rich diet in hypertensive subjects. The present studies demonstrate a potentially important relationship between Na+,K(+)-ATPase activity in the central nervous system and neural regulation of arterial blood pressure.

Anesthesia, General↗
PubMed1991

Phylogenetic analysis of the genus Listeria based on reverse transcriptase sequencing of 16S rRNA.

The phylogenetic interrelationships of members of the genus Listeria were investigated by using reverse transcriptase sequencing of 16S rRNA. The sequence data indicate that at the intrageneric level the genus Listeria consists of the following two closely related but distinct lines of descent: (i) the Listeria monocytogenes group of species (including Listeria innocua, Listeria ivanovii, Listeria seeligeri, and Listeria welshimeri) and (ii) the species Listeria grayi and Listeria murrayi. At the intergeneric level a specific phylogenetic relationship between the genera Listeria and Brochothrix was evident. The sequence data clearly demonstrated that the genus Listeria is phylogenetically remote from the genus Lactobacillus and should not be included in an extended family Lactobacillaceae.

Base Sequence↗
PubMed1991

Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer.

Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists.

Adult↗
PubMed1991

Studies on the role(s) of cerebrospinal fluid osmolality and chloride ion in the centrally mediated pressor responses of sodium chloride.

These studies were designed to investigate whether the centrally mediated pressor effects of hypertonic sodium chloride (NaCl) solutions are triggered in response to changes in the cerebrospinal fluid (CSF) osmolality and whether the chloride ion plays a role in these effects. In Inactin anesthetized, vagotomized rats, alterations in the arterial pressure to cerebroventricular administration (i.c.v.) of various concentrations of NaCl, sodium nitrate (NaNO3), glycerol, creatinine, lithium chloride (LiCl), lithium nitrate (LiNO3) and choline chloride were evaluated. The pressor effects of NaCl were significantly greater than those produced by either glycerol, creatinine and/or NaNO3 solutions. Central effects of NaCl were identical to that of LiCl; likewise, NaNO3 and LiNO3 produced essentially similar increases in the blood pressure. In other words, the two chloride salts produced significantly greater increases in the arterial pressure than the nitrate salts. Choline chloride also produced significant increases in the blood pressure both before and after pretreatment with hemicholinum (i.c.v.). In a separate series of experiments, pretreatment of rats with a vasopressin antagonist (i.v.), significantly attenuated the pressor effects of NaCl, NaNO3 and that of choline chloride whereas after autonomic ganglionic blockade with chlorisondamine, pressor responses of only NaCl, but not those of NaNO3 or choline chloride were significantly inhibited. These data indicate that elevation of either Na+ or Cl- in the CSF facilitates vasopressin secretion and that Na+ and Cl- ions function synergistically in the central nervous system (C.N.S.) to enhance sympathetic activity. The present studies demonstrate that the circumventricular structures in the C.N.S. that participate in the regulation of blood pressure are more responsive to changes in concentrations of Na+ and Cl- rather than to net changes in the CSF osmolality. The data further suggest that the chloride ion contributes to the central pressor effects of NaCl and may play a role in the pathophysiology of salt-dependent hypertension.

Angiotensin Receptor Antagonists↗
PubMed1991

Tension pneumocephalus: treatment with controlled decompression via a closed water-seal drainage system. Case report.

The successful treatment of a patient with tension pneumocephalus by controlled decompression via external drainage is described. The advantage of the technique includes the immediate release of high pressure and the capability of maintaining constant low pressure to enable and facilitate sealing of dural tears. The method has been used in three other patients, leading to resolution of the tension pneumocephalus without recurrence or other complications.

Cerebrospinal Fluid Shunts↗
PubMed1991

Single and multiple dose pharmacokinetics of ticlopidine in young and elderly subjects.

The pharmacokinetics of orally administered ticlopidine hydrochloride, a novel inhibitor of platelet aggregation, were determined both after a single dose and after 21 days of twice daily dosing in 12 young (mean 28.6 years) and 13 elderly (mean 69.5 years) subjects. Concentrations of unchanged ticlopidine in plasma were measured by g.l.c. After a single 250 mg dose of ticlopidine, the mean area under the curve, AUC (0-12 h) was 1.11 micrograms ml-1 h in young subjects and 2.04 micrograms ml-1 h in old subjects (P = 0.002). Mean values of t1/2,z in young and elderly subjects were 7.9 h and 12.6 h, respectively (P = 0.01). Steady state plasma drug concentrations were attained after 14 days of dosing with ticlopidine. After the final dose on day 21, AUC values in elderly subjects were 2-3 times those in young subjects (P less than 0.001). The plasma t1/2,z averaged 4.0 days for young subjects and 3.8 days for elderly subjects (P = 0.7). The longer t1/2,z and higher AUC values after multiple dosing probably reflect an increase in bioavailability of ticlopidine after repeated dosing, saturation of metabolism or insufficient analytical sensitivity to characterize the terminal elimination phase after single dose.

Administration, Oral↗
PubMed1991

Comparison of four different ovarian stimulation protocols in an in vitro fertilisation & embryo transfer programme.

Four different ovarian stimulation protocols were evaluated in an in vitro fertilisation and embryo transfer programme in 208 women (228 treatment cycles). In the rigid protocol (RP), 100 mg of clomiphene citrate (CC) was given from day 3 to day 7 of the menstrual cycle and 300 IU of human menopausal gonadotropin (hMG) was given from day 5 of the menstrual cycle. In the individualised protocol (IP) the same drugs and doses were used as in RP, but the day of initiation of CC depended on the length of the individual's menstrual cycle and hMG was administered from the last day of CC. In the programmed protocol (PP), ovarian function was suppressed with oral contraceptive pills (ethinyl estradiol 30 micrograms and norethisterone 1 mg) started on day 5 of the menstrual cycle for 45 to 70 days. Considering the last day of pill intake as day 0, CC was given for 5 days from day 5 and hMG (300 IU) from day 7. In the alternate day protocol (ADP), 100 mg of CC was administered from day 2 to day 6 and hMG (300 IU) was given on alternate days from day 2 to day 8 or day 10 of the cycle. In all the women, hCG (5000 IU) was administered when the diameter of at least 2 follicles was greater than or equal to 16 mm and estradiol levels were 300 pg/ml/dominant follicle. Patients not showing such a response were not treated further. The cardinal events of IVF-ET such as number of good responders, incidence of oocytes harvested, fertilised and embryos transferred per cycle were compared and it was concluded that the pregnancy rates were highest in women treated by the PP.

Adult↗
PubMed1991

Endometrium--an extragonadal source of inhibin.

Using polyclonal antibodies generated against human seminal plasma inhibin (10.5 KDa), immunocytochemical localization was carried out in paraffin embedded tissue sections of human endometrial biopsies obtained at various phases of the menstrual cycle. A positive reaction which indicated the presence of inhibin was characterized by the presence of golden yellow or brown colour in the cytoplasm of epithelial cells that formed the glands as well as the luminal lining. The stromal cells however, showed negative staining. In early proliferative phase, the endometrial glands exhibited weak positive staining for inhibin which gradually increased and was intense in late follicular and early secretory phases. The intensity of the staining although was not diminished in the glandular epithelium in the mid as well as late secretory phases, the number of cells showing positive staining appeared to be reduced. Incubation of endometrial biopsies in vitro with labelled amino acid and immunoprecipitation of newly synthesized protein with specific antibodies to inhibin indicated that endometrium is capable of de novo synthesizing inhibin. The above results suggest that endometrium is an extra ovarian source of inhibin and the possible role of endometrial peptide in sperm fertilizing capabilities as well as in pre and post implantation events is suggested.

Adolescent↗