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Biomedical subjects

I Khan

Publications and source records attributed to I Khan.

At least 91 records · Page 5Linked to original sources
PubMed1995

Structure-activity relationships of the antimalarial agent artemisinin. 2. Effect of heteroatom substitution at O-11: synthesis and bioassay of N-alkyl-11-aza-9-desmethylartemisinins.

A novel class of artemisinin analogs, N-alkyl-11-aza-9-desmethylartemisinins 17-29, were synthesized via ozonolysis and acid-catalyzed cyclization of precursor amides 5-16. These amides were prepared through condensation of an activated ester of the known intermediate acid 2 with the corresponding primary amine. The analogs were tested in vitro against W-2 and D-6 strains of Plasmodium falciparum and found in some cases to be more active than artemisinin. A comparison of the in vitro testing methods of Milhous and Makler was conducted and gave similar relative antimalarial activities for these artemisinin analogs. Log P values were determined for most of the compounds, but no apparent correlation between log P and in vitro activity was found.

Animals↗
PubMed1995

Kininogen present in rat reproductive tissues is apparently synthesized by the liver, not by the reproductive system.

OBJECTIVE: The purpose of this study was to determine the source(s) of the reproductive tract kininogen and to assess whether kininogen transcription is influenced by reproductive conditions. STUDY DESIGN: Rats in various reproductive states (immature, mature, ovulatory, luteal phase, pregnancy, parturition, postpartum) were used to obtain reproductive tissues (follicles, corpora lutea, oviduct, uterus, testes) and liver. Complementary deoxyribonucleic acid probes for rat prekininogens were used to quantify kininogen messenger ribonucleic acid synthesis. RESULTS: The T-prekininogen complementary deoxyribonucleic acid probe detected a single 1.6 kb message, whereas the k-prekininogen complementary deoxyribonucleic acid probe identified two messages, an abundantly expressed 1.6 kb band and a 2.2 kb band. The source of all the three prekininogen messages appears to be the liver. Naturally occurring reproductive conditions such as ovulation, implantation, and parturition, did not turn on prekininogen message transcription in the rat gonad or genital tract. Only decidualization of the uterus was associated with the induction of kininogen transcription in the liver. CONCLUSION: There appears to be little, if any, contribution of local gene expression to the kininogen present in the reproductive tissues. Apparently, the reproductive tract increases uptake of kininogen from plasma as needed.

Animals↗
PubMed1995

Interleukin 1 beta induces the expression of interleukin 6 in rat intestinal smooth muscle cells.

BACKGROUND/AIMS: The increased expression of several cytokines, including interleukin 6 (IL-6), has recently been reported in a study of the longitudinal muscle and myenteric plexus layers of rat intestine following Trichinella spiralis infection. However, the putative cellular sources and the mechanism underlying the induction of IL-6 in these tissues are presently unknown. The aim of this study was to examine the ability of cultured smooth muscle cells from rat jejunum to produce IL-6 messenger RNA and protein and to investigate the underlying mechanism. METHODS: Cultured smooth muscle cells were treated with human recombinant interleukin 1 beta (HrIL-1 beta). The level of IL-6 messenger RNA was estimated by polymerase chain reaction, and the released IL-6 protein was estimated by bioassay. RESULTS: HrIL-1 beta induced IL-6 messenger RNA expression in the smooth muscle cells in a time- and concentration-dependent manner. This was accompanied by the secretion of IL-6 protein into the medium. The effect of HrIL-1 beta was blocked by the IL-1 receptor antagonist, by actinomycin D, or by prior boiling of the cytokine. CONCLUSIONS: These findings show that HrIL-1 beta interacts with its receptor on smooth muscle cells to induce transcription of the IL-6 gene and to cause the secretion of IL-6. These results indicate that intestinal smooth muscle cells are not only targets for but also a source of cytokine.

Animals↗
PubMed1995

Catastrophic anti-phospholipid syndrome in the absence of IgG anti-cardiolipin antibodies.

The Catastrophic Anti-phospholipid Syndrome (CAPS) is a rare acute clinical syndrome associated with serum anti-phospholipid antibodies (aPL). It is rarely preceded by a precipitating event. It may occur as a primary event or be associated with auto-immune diseases. We report a fatal case occurring post-endoscopic retrograde cholangio-pancreatography (ERCP) in a patient with Systemic Lupus Erythematosus (SLE), positive lupus anticoagulant and negative IgG with positive IgM anti-cardiolipin titres. The diagnostic and therapeutic difficulties of such cases is addressed.

Adult↗
PubMed1995

Messenger RNAs for neurokinin and histamine receptor subtypes in isolated canine colonic crypts.

Functional subtyping of neurokinin and histamine receptors on the canine proximal colon suggested that different receptors were involved in mediating the neural and non-neural effects on ion transport. If the non-neural effects involved direct stimulation of the transporting epithelial cells, mRNA for specific receptor subtypes should be present in colonic crypt cells. Pharmacological data predicted that RNA from such cells would include mRNAs for neurokinin (NK-1) and histamine (H1 and H2) receptors but not for NK-2 or NK-3 receptors. Using published sequences for the above receptors and reverse-transcription polymerase chain reaction, we have noted that isolated canine colonic crypts had mRNA for NK-1 and NK-2 receptors but not for NK-3 receptors. Messenger RNAs for both H1 and H2 receptors were present. The muscularis mucosa and submucosal plexuses had mRNAs for NK-1, NK-3, H1 and H2 receptors but not for NK-2 receptors. The circular and longitudinal muscles expressed mRNA for all three neurokinin and both histamine receptors. Messenger RNA levels for the alpha-1 isoform of the catalytic subunit of the sodium pump were higher in crypts and lower in muscularis mucosa and muscle preparation. Thus these observations provide further evidence for the existence of different receptor subtypes in the canine colon.

Animals↗
PubMed1995

Lead poisoning--a hazard of traffic and industries in Pakistan.

We measured blood lead level, hemoglobin, and urinary amino-levulinic acid (ALA) in industrial workers and in individuals exposed to vehicle smoke. Industrial workers and people exposed to traffic smoke had comparatively higher blood lead levels than the controls (p < 0.0001). Similarly, urinary ALA was 3.82 mg/dL in industrial subjects, 3.68 mg/dL in traffic-exposed people, and 0.8 mg/dL in control subjects (p < 0.001). The hemoglobin level was lower in the industrial group and in the traffic exposure group compared with the control group (p < 0.01). Traffic smoke-exposed persons, such as traffic police staff, had higher blood lead level than those handling lead material, Government Transport Service (GTS) workshop staff. The length of exposure showed no relationship with the lead levels. However, a positive correlation was observed between the duration of exposure and urinary ALA in both sample groups. The major signs and symptoms of the population studied included headache, generalized body pain, hypertension, and depression.

Adult↗
PubMed1994

Fourth isoform of preprotachykinin messenger RNA encoding for substance P in the rat intestine.

Three different isoforms of preprotachykinin mRNA (PPT mRNA) encode for substance P and related neuropeptides (1). Here we report a fourth isoform of PPT mRNA which is generated by alternative exclusion of exon-7 and exon-6 from the PPT mRNA. It was present mainly in ileal smooth muscle and mucosa, colon, heart and brain and low level of this mRNA was detected in the jejunal smooth muscle and mucosa. This was not detected in the kidney or uterus. The level of this PPT mRNA was enhanced significantly by 60% during colitis in rat induced by trinitro benzene sulphonic acid.

Alternative Splicing↗
PubMed1994

Expression of cytokines in the longitudinal muscle myenteric plexus of the inflamed intestine of rat.

BACKGROUND/AIMS: Trichinella spiralis infection in the rat produces mucosal injury and inflammation and causes changes in muscle function and neurotransmitter release in the longitudinal muscle myenteric plexus (LMMP). Whether these changes in LMMP reflect the production of inflammatory mediators in the LMMP remains unknown. The objective of this study was to investigate the profile of interleukins (IL) 1-alpha, 1-beta, and 6 and tumor necrosis factor (TNF) alpha in the LMMP of infected rats. Because muscle changes are T-cell dependent, we also studied the cytokine profile in infected athymic rats. METHODS: Cytokine messenger RNA (mRNA) was examined using semiquantitative polymerase chain reaction, and protein was measured by enzyme-linked immunosorbent assay, radioimmunoassay, or bioassay. RESULTS: There was increased expression of IL1-alpha and -beta, IL-6, and TNF-alpha mRNA and protein in the LMMP of both euthymic and athymic infected rats. Increased expression of each cytokine was observed by 24 hours postinfection and, in the case of IL1-beta and TNF-alpha, remained elevated by day 6 postinfection. CONCLUSIONS: Mucosal injury following T. spiralis infection is accompanied by enhanced expression of proinflammatory cytokines in the LMMP. The expression of IL1-, IL-6, and TNF-alpha in infected athymic rats suggests that these cytokines do not contribute to the changes in muscle growth or contraction but may mediate the previously described changes in neurotransmitter release in this model.

Animals↗
PubMed1994

Differential c-jun gene expression with tonically administered steroids in rat ovary and uterus.

OBJECTIVE: The purpose of this study was to evaluate the induction of the early regulatory gene c-jun in response to tonic exposure to estradiol and progesterone in rat ovary, uterus, and adrenal tissues. STUDY DESIGN: Pellets containing estradiol-17 beta, progesterone, and estradiol-17 beta plus progesterone were placed subcutaneously in immature female Sprague-Dawley rats (N = 24). The ovary, uterus, and the adrenal were evaluated for c-jun expression by Northern analysis at 24 and 48 hours. RESULTS: The c-jun messenger ribonucleic acid expression in the ovary and adrenal gland was inhibited with high, nonphysiologic doses of estradiol in progesterone and was induced with physiologic levels of estradiol. Physiologic levels of progesterone do not appear to influence the expression of c-jun in the ovary or adrenal gland. Uterine c-jun expression to estradiol and progesterone is generally the opposite of that observed in the ovary. CONCLUSION: These findings suggest that there is both tissue and dose specificity of c-jun gene expression in steroidogenic and steroid-responsive tissues when steroid hormones are tonically administered.

Adrenal Glands↗
PubMed1994

Impairment of the cellular immune response in acute murine toxoplasmosis: regulation of interleukin 2 production and macrophage-mediated inhibitory effects.

Depression of the cellular immune response to Toxoplasma gondii has been reported in both mice and humans. The present study was undertaken to determine the kinetics and mechanism of the observed downregulation of interleukin 2 (IL-2) production during experimental murine toxoplasmosis. For these investigations, the cell-mediated immune response to the wild type (PTg) was compared with that to the less-virulent mutant parasite (PTgB), which is deficient in the major surface antigen, p30 (SAG-1). Spleen cells from infected A/J mice failed to proliferate in response to Toxoplasma antigens during the first week of infection. Both PTg- and PTgB-infected A/J mice exhibited a significant reduction in the concanavalin A (Con A)-induced lymphoproliferative response. Further, the response of splenocytes from mice infected with the wild-type parasite was significantly diminished compared with that of mice infected with PTgB. The lymphoproliferative response to Con A reached its nadir at day 7 and remained below control levels for at least 14 days postinfection. By day 21 postinfection, the response to Con A and to Toxoplasma antigens was restored to the level observed prior to day 7. Con A-stimulated culture supernatants of spleen cells from mice on day 7 postinfection contained significantly less IL-2 than normal mice. There was no significant difference in the numbers of binding sites or capacity of high-affinity IL-2 receptors between infected and normal mouse splenocytes as determined by Scatchard analysis. Exogenous IL-2 at different concentrations failed to restore the proliferative response of lymphocytes from infected mice to Con A. Adherent macrophages from 7-day-infected mice were able to suppress IL-2 production by normal splenocytes following stimulation with Con A. The inhibitory activity mediated by infected cells was reversed by the antibody to IL-10 but not transforming growth factor beta. There were insignificant levels of nitric oxide production in both infected and normal splenocytes. These results indicate that during acute murine toxoplasmosis, there is a well-defined period (day 7) during which both the T-cell mitogen and parasite antigen-associated lymphoproliferative response are reduced. Further, there is a reduction in the production of IL-2 and an increase in IL-10, which appear to mediate, in part, the observed downregulation of immunity to T. gondii.

Acute Disease↗
PubMed1994

Review: scheduling drugs and national legal controls the need for research.

The system of scheduling narcotic drugs and psychotropic substances under national legislation does not always correspond to the system of scheduling under the international drug control treaties. Even though many drugs have been scheduled under the international drug control treaties, few studies have been done to identify what happens when drugs are scheduled at the national level. Preliminary studies seem to indicate that non-availability and higher prices are two problems which are associated with the scheduling process at the national level. Further research is needed to have a better understanding of the dynamics of the scheduling process and the impact of national controls.

Journal Article↗
PubMed1993

Localization of immunoreactive epidermal growth factor receptor in neonatal and adult rat hippocampus.

The regional and developmental expression of epidermal growth factor (EGF) receptor in rat hippocampus was investigated utilizing immunocytochemical techniques at the light and electron microscopic levels. EGF receptor immunoreactivity in adult hippocampus was compared to that found at postnatal day 7 (P7). While the receptor was observed in P7 hippocampus, immunostaining was more prominent in the adult hippocampus, especially in the pyramidal CA2 field. Ultrastructural analysis of this region revealed that the receptor was localized to the cell bodies of both P7 and adult neurons rather than the axons or dendrites. The expression of EGF receptor in selected regions of the adult brain was verified by Western blotting. These results demonstrate the presence of EGF receptor in rat hippocampus as early as P7, localize the receptor to the pyramidal cell body, and establish the hippocampal formation, particularly CA2, as a major site of EGF receptor expression in rat brain.

Aging↗
PubMed1993

In situ hybridization and immunocytochemical localization of SERCA2 encoded Ca2+ pump in rabbit heart and stomach.

Heart tissue contains large amounts of the protein encoded by the Ca2+ pump gene SERCA2. The SERCA2 RNA can be spliced alternatively to produce mRNA encoding the proteins SERCA2a and SERCA2b which differ in their C-terminal sequences. In this study we report the tissue distribution of SERCA2a and SERCA2b isoforms by in situ hybridization to rabbit heart and stomach. The expression of SERCA2 mRNA was high in myocardial cells, being the highest in the atrial region. In contrast, there was more SERCA2 protein in Western blots in ventricles than in atria. Myocardial cells expressed predominantly the mRNA for the isoform SERCA2a. Whereas the stomach smooth muscle and the neuronal plexus expressed SERCA2 at levels much lower than myocardial cells, the expression was very high in the stomach mucosa. Mucosa contained mainly the mRNA for SERCA2b. From immunocytochemistry it was concluded that the anti-heart SR Ca2+ pump antibody IID8 reacted much better with heart and surface mucosal cells in the stomach than with the stomach smooth muscle, and that IID8 reactivity was intracellular. In contrast PM4A2B, an antibody against the plasma membrane Ca2+ pump, reacted well with heart and stomach smooth muscle, plexus and mucosa, and its localization appeared to be in the plasma membrane. Thus, stomach smooth muscle expressed SERCA2b mRNA and protein at low levels, mucosa expressed SERCA2b mRNA and protein at high levels, atria and ventricle expressed SERCA2a mRNA and protein at high levels, mRNA being more in atria, but protein being more in ventricles.

Animals↗
PubMed1993

Separation of glucooligosaccharides and polysaccharide hydrolysates by gradient elution hydrophilic interaction chromatography with pulsed amperometric detection.

Commercial glucooligosaccharide mixtures (Polycose) and polysaccharide hydrolysates (acid and enzymatic) were fractionated by hydrophilic interaction chromatography and observed by pulsed amperometric detection. Seven peaks were observed when 625 ng of glucose oligomers in Polycose were fractionated. The between-run precision of retention times (n = 10, 100 micrograms, 15 peaks) ranged from a relative standard deviation (R.S.D.) of 0.09 to 0.40%; between-run precision of peak areas (n = 10) for the same separations had values that ranged from 2.66 to 14.4%. Injection-to-injection time was 48 min. When polysaccharide hydrolysates were fractionated using a gradient program capable of resolving all of the oligosaccharide species, dextran-derived alpha-(1-->6)-glucooligosaccharides were retained to a greater degree than amylose-derived alpha-(1-->4)-glucooligosaccharides, which were retained to a greater degree than beta-(2-->1)-fructooligosaccharides derived from inulin. Excluding the peaks that eluted before glucose or fructose, 25 to 35 peaks were observed after fractionation of the hydrolysates. Differences in elution profiles were observed between acid and enzymatic hydrolysis products of the same polysaccharide as well as between hydrolysis products of different polysaccharides. In conjunction with high-performance size-exclusion chromatography, the method demonstrated the effect of preheating starch before hydrolysis with isoamylase.

Chromatography, Liquid↗
PubMed1993

Differential induction of c-jun expression by PGF2-alpha in rat ovary, uterus and adrenal.

The influence of PGF2 alpha on c-jun gene expression in ovary, uterus and adrenal was examined. Three and seven day postovulatory PMSG primed immature rats received 500 ug PGF2 alpha by two subcutaneous injections 8 hours apart. Control rats received saline. Animals were sacrificed 30 minutes after the second injection of PGF2 alpha. Tissues were obtained and frozen in liquid nitrogen. RNA extracted from ovary, uterus and adrenal was analyzed by Northern and slot blot. c-jun was expressed differentially in these organs. An increase in c-jun expression by PGF2 alpha treatment occurred in the ovary but not in the adrenal and uterus. The effect of PGF2 alpha on c-jun was stronger in older compared to younger corpora lutea. These results indicate differential regulation of c-jun by PGF2 alpha in steroidogenic and steroid responsive tissues and that c-jun might be linked to the mode of action of PGF2 alpha in luteolysis.

Adrenal Glands↗
PubMed1993

Abundance of heteronuclear and messenger RNA for internal Ca pump in stomach smooth muscle and myocardium.

The sarcoplasmic reticulum Ca pump gene SERCA2 is alternatively spliced to express mRNA encoding the protein SERCA2a in heart and SERCA2b in stomach smooth muscle. The expression of SERCA2 protein in heart is 70 +/- 10 fold that in stomach smooth muscle. To understand the mechanism underlying this tissue difference in the expression level, a comparison is made of their mRNA and heteronuclear RNA (hn-RNA) contents. A 72 bp intron present in the gene encoding SERCA2a/b was cloned and sequenced. By reverse transcription of total RNA followed by PCR using primers based on the sequence of this intron and the cDNA sequences flanking it, a value of 0.37 +/- 0.03 was obtained for the ratio heart hn-RNA/mRNA:stomach hn-RNA/mRNA. Similarly, a ratio of 3.4 +/- 0.5 was obtained for heart:stomach mRNA/28S values. This value was slightly lower but statistically similar to a value of 5.7 +/- 1.8 obtained for the heart:stomach mRNA/poly A+ RNA obtained by Northern blot analysis using a conserved region SERCA2 cDNA probe. Based on mRNA/28S ratio of 3.4 +/- 0.5 and hn/mRNA ratio of 0.37 +/- 0.03, the ratio of heart:stomach for hn-RNA/28S was 1.2 +/- 0.2. Thus, heart which expresses SERCA2a contains 70 +/- 10 times more protein, 3.4 +/- 0.5 times more mRNA and only 1.2 +/- 0.2 times more hn-RNA for this message than the stomach smooth muscle which expresses SERCA2b.

Animals↗
PubMed1993

Expression of the internal calcium pump in pregnant rat uterus.

Uterine contraction to agents such as oxytocin during labour may utilize Ca2+ sequestered by Ca2+ pump into the sarcoplasmic reticulum (SR). Uterus expresses the SR Ca2+ pump gene SERCA2 as the mRNA splice which encodes the protein SERCA2b. The expression of SERCA2 mRNA and protein was monitored in uteri of day 15 pregnant and delivering rats. The ratio of SERCA2 mRNA to 28S RNA increased by 20% from day 15 to delivery. SERCA2 protein examined by two antibodies increased by 54-55%. Ca2+ dependent acylphosphate intermediate of 115 kD corresponding to SERCA2 also increased 72% during this period. Thus, there is an increase in the SERCA2 expression from day 15 to delivery.

Acylation↗