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Biomedical subjects

I Khan

Publications and source records attributed to I Khan.

At least 109 records · Page 6Linked to original sources
PubMed1993

The effect of naloxone on cerebral blood flow and glucose metabolism in patients with complex partial seizures.

We used positron emission tomography with [15O]water and [18F]fluoro-2-deoxyglucose (FDG) to study the effect of naloxone on cerebral blood flow (CBF) and glucose metabolism (LCMRglc) in patients with complex partial seizures. There was no effect on glucose metabolism, but blood flow was reduced 7-12% 45-60 min after infusion of 1 mg/kg naloxone, as was the degree of lateral temporal CBF asymmetry in patients with > 10% baseline hypoperfusion. Endogenous opiates are involved in regulation of human CBF, and possibly in hypoperfusion in epileptic foci. Since [18F]FDG PET measures mean LCMRglc over the tracer uptake and scanning periods, it is inferior to [15O]H2O PET for detecting drug effects which may be time dependent.

Brain↗
PubMed1993

Altered expression of sodium pump isoforms in the inflamed intestine of Trichinella spiralis-infected rats.

We used polymerase chain reaction (PCR) and Northern analysis to examine the effect of Trichinella spiralis infection on mRNA expression of sodium pump isoforms in rat intestine. 28S RNA was coamplified as an internal standard, and the abundance of the isoformic mRNA was expressed relative to 28S RNA. As assessed by PCR and Northern analysis, the alpha 1- and beta 1-subunits were expressed in the jejunum and ileum of noninfected control rats. However, in the jejunum the levels were suppressed after 24 h of infection. The suppression became maximal by day 6 and was reversed to normal by day 23 postinfection (PI). In contrast, no suppression was observed in the noninflamed ileum of infected rats. Further analysis revealed that alpha 1-mRNA was suppressed in jejunal mucosa by 89% and in longitudinal muscle-myenteric plexus by 62% but was not suppressed in circular muscle. Western blot analysis revealed a 61% decrease in the alpha 1-subunit protein in the mucosa and a 62% decrease in longitudinal muscle, whereas there was no change in the alpha 1-protein in circular muscle on day 6 PI. In contrast, marked (89%) suppression of beta 1-mRNA was observed only in the mucosa; there was no change in either circular or longitudinal muscle on day 6 PI. These results indicate that T. spiralis infection in the rat is accompanied by a significant decrease in the alpha 1-subunit of the sodium pump in longitudinal muscle. This reduction could result from altered regulation involving pretranslational changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Polymerase chain reaction assay of mRNA using 28S rRNA as internal standard.

A method is developed for PCR assay of mRNA using 28S rRNA as internal standard and its applicability is reported for 4 types of mRNA. It consists of reverse transcription of total RNA using primers selective for 28S rRNA and the message of interest. Routinely the 28S reaction mix is diluted 20,000-fold and the dilution error is minimized by adding 10 microCi of 3H2O before the dilution and determining the level of 3H before and after the dilution. Aliquots from the diluted 28S mix and the undiluted reverse transcripts are co-amplified by PCR in the presence of 32P-dATP. The samples are analyzed by electrophoresis, bands detected by autoradiography and in each lane the ratio is determined between cpm in the band of interest and cpm in the 28S band. The ratio is a measure of the level of mRNA in the sample and can be used to monitor changes in mRNA during treatments, development and pathogenesis.

Animals↗
PubMed1992

Calcium pump isoforms: diversity, selectivity and plasticity. Review article.

Ca2+ pumps are essential for removing cytosolic Ca2+ either across the plasma membrane (PM) or into internal organelles such as the sarcoplasmic reticulum (SR). Four genes (PMCA1, PMCA2, PMCA3 and PMCA4) have been reported to encode the PM Ca2+ pumps and three (SERCA1, SERCA2 and SERCA3) to encode the SR Ca2+ pumps. The PM Ca2+ pumps are stimulated by calmodulin, the SR Ca2+ pumps encoded by SERCA1 and SERCA2 are stimulated by phospholamban while the product of SERCA3 may be regulated directly by cAMP-dependent protein kinase. Alternative splicing of the primary transcripts of several of these genes has been reported to occur in a tissue selective manner and for others to alter during ontogeny. For the PM Ca2+ pump, alternative RNA splicing may result in isoforms with altered cyclic nucleotide dependent protein kinase sensitivity. The diversity in distribution of Ca2+ pump isoforms and their regulatory factors when coupled with different Ca2+ entry mechanisms allows for tissue selectivity and plasticity in stimulus-response coupling. The roles of various Ca2+ pump isoforms, the rationale behind their tissue selective expression and the plasticity in this expression are among the new challenges to researchers in this field.

Animals↗
PubMed1992

International regulation of benzodiazepines.

1. The UN Convention 1971 on Psychotic substances requires the World Health Organization to recommend psychotropic substances for international control. 2. This convention is based on evaluating the benefit and risk ratio, in particular on the public health and social problems associated with its use. 3. The UN Commission on Narcotic Drugs takes a final decision on these recommendations and is then binding in countries which are party to the convention. 4. Presently 34 commercially available benzodiazepines are under international control at minimum level, schedule IV of the 1971 convention, to be available on the physicians' prescription and not over the counter.

Anti-Anxiety Agents↗
PubMed1992

Urine transparency as an index of absence of infection.

A visual assessment of the clarity of urine was used as an exclusion test to indicate the absence of infection; verified by dipslide culture, it was applied to 363 urine samples collected from patients attending 2 adult nephrology clinics over a period of 6 months. The crimped aluminium bowl used for collection of samples assisted the assessment of clarity. The sensitivity of the method compared with dipslide culture was 73%, with specificity and efficiecy both 58%. The predictive value of a negative test (clarity) was 97% with a false negative rate of 3%, enabling this simple examination to be used as an exclusion test for further testing. In simple terms, a clear urine is unlikely to be infected. It is also an advantage to have an immediate indicator of the absence of infection available at the clinic. Analysis of only those urines assessed as cloudy could result in financial savings and, from the clinics, a 56% reduction in workload.

Adolescent↗
PubMed1992

Effect of inflammation of enteric nerves. Cytokine-induced changes in neurotransmitter content and release.

The results of our previously published work provide evidence of inflammation-induced functional disturbances in the enteric nervous system. Data presented in this paper describe our preliminary results indicating that the altered function in enteric nerves in the nematode-infected rat model of intestinal inflammation is mediated by interleukin-1. This is based on the ability of the exogenous cytokine to mimic changes observed in the model, and on the ability of a specific IL-1 antagonist to attenuate these changes. In addition, we have identified mechanisms underlying the actions of IL-1 in the myenteric plexus. Our data are consistent with a direct interaction between the cytokine and neural membranes. In addition, the delayed effect of IL-1 beta on neurotransmitter release appears to be due to the release of endogenous IL-1, most likely from macrophage-like cells in the myenteric plexus (Fig. 3). If such cells possess receptors for neuropeptides, as has been found with macrophages elsewhere in the gut, a neuroimmune axis would exist in the myenteric plexus. Thus, the finding of a source of IL-1 in the plexus of the noninflamed intestine invites speculation on a neuromodulatory role of the cytokine within the enteric nervous system.

Animals↗
PubMed1992

P450(17 alpha) and P450SCC gene expression and regulation in the rat placenta.

To examine the developmental expression and regulation of P450SCC and P450(17 alpha) in the rat placenta, trophoblast and decidual tissue were removed by dissection from conceptuses obtained from rats on selected days of pregnancy. Total cellular and poly(A)+ RNA and microsomal and mitochondrial fractions were isolated and analyzed for the presence of P450(17) alpha and P450SCC messenger RNA (mRNA) and protein by Northern and Western blot analysis. P450(17) alpha and P450SCC mRNA were detected in the trophoblast but not in the decidual tissue. Western blot studies demonstrated that the immunoreactive P450(17) alpha in the rat placenta is a 79-kilodalton protein, having a slower mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than has been reported for other tissue. Antiserum preabsorbed with pure P450(17) alpha was unable to detect this protein, and immunoprecipitation indicated that it is associated with enzyme activity. Development studies have revealed that the two steroidogenic enzymes are differentially expressed during the progression of pregnancy. Whereas P450SCC mRNA and protein increase abruptly between days 10-12 of pregnancy, decline thereafter, and remain low, those of P450(17) alpha increase slowly and progressively, peaking on day 18 and declining just before parturition. It is the changes in P450(17) alpha and not that of P450SCC which appear to be intimately linked to the previously reported changes in placental production of androgen. To examine whether P450(17) alpha and/or P450SCC became expressed from midpregnancy because of the rapid decline in LH that occurs at this stage, pregnant rats were treated with low but sustained levels of human CG (hCG) in order to prevent the drop in LH activity. hCG treatment caused a remarkable down regulation in the expression of both P450SCC and P450(17) alpha message and protein. In summary, the results of this investigation have established, for the first time, the presence of messages for both P450(17) alpha and P450SCC in the trophoblast tissue forming the rat placenta. The results have revealed that these two enzymes are differentially expressed during the progression of pregnancy and that the expression of their genes is down-regulated by LH/hCG.

Androgens↗
PubMed1992

Hormonal and immunological characterization of the 32 kilodalton ovarian-specific protein.

Recent studies from this laboratory have shown that the large luteal cell of the pregnant rat contains an abundant 32 kilodalton (32K) phosphoprotein which is up-regulated by estradiol. In order to assess the potential importance of this protein and to more fully understand its function, a specific polyclonal antibody was produced against the 32K and was used to examine its intraovarian localization, its tissue specificity, and its developmental regulation. Immunocytochemical localization of the 32K in the ovary of the pregnant rat found this protein to be selectively and abundantly expressed in the corpus luteum. Immunofluorescence study of small and large luteal cell populations clearly revealed an extensive localization of the 32K in the large luteal cells. Western blot analysis revealed that the 32K was absent from all steroidogenic and nonsteroidogenic tissues. Whereas this protein was absent from all other tissues examined in the rat, it was clearly expressed in corpora lutea of different animal species, including the mouse, hamster, cow, human, and pig. Although undetectable by immunohistochemistry, Western blot analysis showed this protein to be present in the follicle but at levels markedly lower than in the corpus luteum. Analysis of theca and granulosa cells revealed the presence of the 32K in both cell types. To further examine the developmental expression of this protein throughout gestation, Western blot analysis of microsomal fractions isolated from rat corpora lutea on days 3-21 of pregnancy was performed. The 32K was detected at low levels in early pregnancy, increased markedly on day 11, reached a peak on days 14-15, and remained elevated through day 21. Treatment with estradiol and PRL increased the content of the 32K in the corpus luteum. Human CG, known to cause follicular development to the preovulatory stage and to enhance luteal estradiol synthesis, also increased levels of the 32K in the corpus luteum, while it concomitantly decreased this protein in the follicle. In summary, the presence of a unique ovarian-specific 32 kilodalton protein has been established. This protein, which is present in low abundance in theca and granulosa cells, is localized to the large luteal cell and becomes abundantly expressed during midpregnancy, a time when there is a remarkable increase in luteal cell size and activity. Results of this study also demonstrate a multihormonal regulation of the 32K by tropic hormones. Thus, because of its apparent uniqueness and its timely and highly regionalized expression, the 32K may play a central role in the regulation of corpus luteum growth and function.

Animals↗
PubMed1992

Ca pump messenger RNA expression in pregnant rat uterus.

Rat uterus expresses transcripts for the plasma membrane Ca pump PMCA1 and for the sarcoplasmic reticulum Ca pump SERCA2. Uterus contains two mRNA isoforms for PMCA1, one encoding a cyclic nucleotide insensitive Ca pump (PMCA1a) and the other encoding a cyclic nucleotide sensitive pump (PMCA1b). The relative ratio of mRNA to 28S RNA for PMCA1a or PMCA1b and the amount of poly A+ RNA per microgram total RNA obtained from uteri of rats pregnant for 15 days and for parturient rats was similar but the ratio of SERCA2 mRNA to 28S RNA was significantly higher in the parturient rats.

Animals↗
PubMed1991

Expression of cyclic-nucleotide-sensitive and -insensitive isoforms of the plasma membrane Ca2+ pump in smooth muscle and other tissues.

cDNA clones encoding the plasma membrane Ca2+ pump isoform PMCA1 were obtained from rabbit stomach smooth muscle. The PMCA1 gene has a 154 base exon which can be alternatively spliced. In splices containing 0, 87 or 114 bases of this exon, the mRNA downstream from this position encodes a protein containing the peptide sequence Lys-Arg-Asn-Ser-Ser (KRNSS), which can be phosphorylated by cyclic-nucleotide-sensitive protein kinase. However, in those splices containing 154 bases, the mRNA encodes a protein that does not contain this sequence. The cDNA clone obtained in this study did not contain the latter exon, and thus it coded for KRNSS. The presence of the various splices of PMCA1 was determined in stomach smooth muscle and other tissues by reverse transcription followed by a polymerase chain reaction. Percentage of transcripts encoding the potentially cyclic-nucleotide-sensitive isoform in various tissues were as follows: liver, 100%; stomach mucosa, 100%; heart, 100%; stomach smooth muscle, 86%; aorta, 83%; brain, 55%. Thus brain was the only tissue which expressed a very high proportion of the isoform of PMCA1 that is insensitive to cyclic-nucleotide-dependent protein kinases.

Amino Acid Sequence↗
PubMed1991

Inhibition and stimulation of rat luteal protein phosphorylation by protein kinase effectors.

Estradiol-17 beta (E2) predetermined protein phosphorylation systems have been identified recently in midpregnant rat corpus luteum. Major type protein kinase activities in these systems were explored here using as probes protein kinase inhibitors. Luteal nuclear, mitochondrial, microsomal and cytosolic fractions were obtained from rats hysterectomized and hypophysectomized on day 12 of pregnancy and then treated for 72 h with E2. In vitro phosphate transfer from [gamma-32P]ATP was monitored by SDS-PAGE followed by autoradiography. Polymyxin B (PMB), 1-200 microM, a PKC inhibitor, completely blocked, in a dose dependent manner, the Ca2+ phospholipid (PL) stimulated radiolabeling of nuclear fraction Mr 79,000 substrate(s) as expected. Similarly, the calmodulin (CaM) antagonist compound 48/80, 1-20 micrograms/ml, inhibited the Ca2+/CaM-dependent phosphorylation of the microsomal fraction Mr 60,000 and Mr 56,000 proteins. The Ca2+ PL-enhanced labeling of mitochondrial fraction Mr 76,000 substrate(s) was only partially susceptible to inhibition by PMB or compound 48/80. Studies of microsomal fraction phosphoprotein bands not stimulated by added cofactors indicated that the radiolabeling of Mr 75,000 protein(s) was partially blocked by compound 48/80 but not by PMB. Phosphate transfer to Mr 41,000 protein(s) was inhibited by the cAMP-dependent kinase protein inhibitor (PKI), while the phosphorylation of Mr 31,000 protein(s) was refractory to all inhibitors employed here. Surprisingly, regardless of hormonal pretreatment, PMB and compound 48/80 activated in every subcellular fraction the cofactor independent appearance of at least one phosphoprotein band, between Mr 87,000-99,000. This novel observation should be instrumental in understanding the actions of these compounds towards living cells.

Animals↗
PubMed1991

Expression of isoforms of internal Ca2+ pump in cardiac, smooth muscle and non-muscle tissues.

Smooth muscle and several non-muscle tissues contain mRNA for an alternative splice of the mRNA for the cardiac sarcoplasmic reticulum (SR) Ca,Mg-ATPase. Based on amino acid composition deduced from cDNA sequences the cardiac isoform (Ic) is 110 kDa while the smooth muscle and the non-muscle isoform (Is) is 115 kDa. This prediction in their molecular masses was tested at the protein level in rabbit stomach, aorta, uterus and vas deferens smooth muscles; stomach mucosa, brain, liver, kidney and heart. The major species of the acylphosphates formed in the presence of Ca2+ and electrophoresed in acid SDS-acrylamide gels were 5 kDa smaller for the heart (Ic) than those for all the other tissues (Is). The size difference was also confirmed in Western blots using a monoclonal antibody which binds to both Is and Ic. Thus consistent with the mRNA splices for the internal Ca2+ pumps previously reported to be present in these tissues, rabbit heart expresses predominantly the Ca2+ pump protein Ic and the various smooth muscle, mucosa, brain, liver and kidney express mainly the isoform Is.

Animals↗