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Biomedical subjects

A Khan

Publications and source records attributed to A Khan.

At least 37 records · Page 2Linked to original sources

Improved human islet isolation using nicotinamide.

We investigated the effects of nicotinamide (NA) supplementation of the processing medium during islet isolation. One hundred and two human pancreata were processed for clinical transplantation after preservation either in the University of Wisconsin (UW) or using the two-layer method (TLM). Pancreata were then divided into four groups and retrospectively analyzed. Group I: UW preservation followed by processing without NA, Group II: UW preservation and processing with NA, Group III: TLM preservation without NA, Group IV: TLM preservation with NA. We observed a significant increase in islet yield in Group II (4343+/-348 IEQ/g) [mean+/-SEM], compared to Group I (2789+/-348 IEQ/g) (p=0.005). Similarly, a significant increase in islet yield was observed when NA was used in the processing of organs preserved with TLM (Group IV: 5538+/-413 vs. Group III: 3500+/-629; p=0.02). Furthermore islet yield was higher in Group IV than in Group II (p<0.05). The percentages of preparations that qualified for transplantation were 25, 47, 45, 69% in Groups I, II, III, IV, respectively. Addition of NA to the processing medium significantly improved islet yields in both the UW and TLM preservation protocols, allowing for a higher percentage of islet preparations to qualify for clinical transplantation.

Adenosine↗

Search for T, CP, and CPT violation in B0-B0 mixing with inclusive dilepton events.

We report the results of a search for T, CP, CPT, and violation in B0-B0 mixing using an inclusive dilepton sample collected by the BABAR experiment at the PEP-II factory. Using a sample of 232 x 10(6) BB pairs, we measure the T and CP violation parameter |q/p| - 1 = (-0.8 +/- 2.7(stat) +/- 1.9(syst) x 10(-3), and the CPT and CP parameters Imz = (13.9 +/- 7.3(stat) +/- 3.2(syst)) x 10(-3) and Delta Gamma x Rez = (7.1 +/- 3.9(stat) +/- 2.0(stat)) x 10(-3) ps(-1). The statistical correlation between the measurements of Imz and Delta Gamma x Rez is 76%.

Journal Article↗

Search for the rare decay B0-->tau+tau- at BABAR.

We present the results of a search for the decay B0-->tau+tau- in a data sample of (232+/-3)x10(6) Upsilon(4S)-->BB decays using the BABAR detector. Certain extensions of the standard model predict measurable levels of this otherwise rare decay. We reconstruct fully one neutral B meson and seek evidence for the signal decay in the rest of the event. We find no evidence for signal events and obtain Beta(B0->tau+tau-)<4.1x10(-3) at the 90% confidence level.

Journal Article↗

Observation of Upsilon(4S) decays to pi(+)pi(-)Upsilon(1S) and pi(+)pi(-)Upsilon(2S).

Observation of Upsilon(4S) decays to pi(+)pi(-)C and pi(+)pi(-)Upsilon(2S)We present the first measurement of Upsilon(4S) decays to pi(+)pi(-)Upsilon(1S) based on a sample of 230 x 106(4S) mesons collected with the BABAR detector. We measure the product branching fractions Beta(Upsilon(4S) --> pi(+)pi(-)Upsilon(1S)) x BetaUpsilon(1S) --> mu(+)mu(-) = (2.23 +/- 0.25(stat) +/- 0.27(syst))x 10(-6) and Beta(Upsilon(4S) --> pi(+)pi(-)Upsilon(2S) x Beta(Upsilon(2S) --> mu(+)mu(-))=(1.69 +/-0.26(stat) +/- 0.20(syst)) x 10(-)6, from which we derive the partial widths Gamma(Upsilon(4S) --> pi(+)pi(-)Upsilon(1S))=(1.8 +/-0.4) keV and Gamma(Upsilon(4S) --> pi(+)pi(-)Upsilon(2S))=(2.7 +/- 0.8) keV.

Journal Article↗

Determinations of from inclusive semileptonic decays with reduced model dependence.

We report two novel determinations of /|Vub/ with reduced model dependence, based on measurements of the mass distribution of the hadronic system in semileptonic B decays. Events are selected by fully reconstructing the decay of one B meson and identifying a charged lepton from the decay of the other B meson from Upsilon(4S)-->BB events. In one approach, we combine the inclusive B-->Xulambdav rate, integrated up to a maximum hadronic mass mX<1.67 GeV/c2, with a measurement of the inclusive B-->Xsgamma photon energy spectrum. We obtain /Vub/=(4.43+/-0.38stat+/-0.25syst+/-0.29theo) x 10-3. In another approach we measure the total B-->Xulambdav rate over the full phase space and find /Vub/=(3.84+/-0.70stat+/-0.30syst+/-0.10theo) x 10-3.

Journal Article↗

Role of fusogenic non-PC liposomes in elicitation of protective immune response against experimental murine salmonellosis.

Earlier we have demonstrated that novel fusogenic liposomes made up of lipid from Escherichia coli (escheriosomes) have strong tendency to fuse with the plasma membrane of target cells and thereby delivering the entrapped contents into their cytosol. The delivery of entrapped antigen in cytosol of the target cells ensues its processing and presentation along with MHC class I pathway that eventually elicit antigen specific cytotoxic T cells. The result of the present study revealed that immunization of BALB/c mice with escheriosome-encapsulated Salmonella typhimurium (S. typhimurium) cytosolic antigens resulted in the augmentation of antigen specific cytotoxic T cell lymphocyte as well as IgG responses. In contrast, free or conventional liposome (PC liposome) encapsulated antigen failed to induce CD8+ CTLs in the immunized animals. Further, immunization with escheriosome-encapsulated antigen resulted in significant enhancement in the release of IFN-gamma and IgG2a in the experimental animals. Interestingly, the immunization with escheriosome-encapsulated antigen resulted in upregulation of CD80 and CD86 on the surface of antigen presenting cells (APCs) as well. Finally, the results of the present study reveal that immunization of animals with escheriosomes encapsulated antigen protected them against virulent S. typhimurium infection. This was evident by increased survival, and reduced bacterial burden in vital organs of the immunized animals. The data of the present study suggest that escheriosomes can emerge as an effective vehicle for intracellular delivery of antigen and thus hold promise in development of liposome based vaccine against Salmonella and other intracellular pathogens.

Adjuvants, Immunologic↗

Protection capability of recombinant plasmid DNA vaccine containing VP2 gene of very virulent infectious bursal disease virus in chickens adjuvanted with CpG oligodeoxynucleotide.

In the present study the efficacy of recombinant plasmids DNA vaccine encoding VP2 gene of very virulent strain of infectious bursal disease virus (vvIBDV) isolated from Pakistan was investigated with or without coadministration of cytocine-phosphate-guanine oligodeoxynucleotide (CpG ODN) to protect the chickens against the disease. VP2 gene of vvIBDV was successfully amplified by reverse transcription-polymerase chain reaction (RT-PCR) and was cloned into eukaryotic expression plasmid vector, which consisted of human cytomegalovirus (HCMV) immediate early enhancer and promoter, adenopartite leader sequences and SV-40 polyadenylation signal, and this was designated as pRc-VP2. Seven-day-old maternal antibodies free chickens were intramuscularly injected with 500 microg of pRc-VP2 with or without CpG ODN twice at 1-week interval. At the age of 21 days the broiler chickens were challenged with 10(5) EID(50) of homologous strain of IBDV and observed for 14 days post-challenge. Immunization with pRc-VP2 plus CpG ODN conferred protection in 93% of the chickens as evidenced by the absence of clinical signs, atrophy of bursa of Fabricius (BF) and mortality followed by the group vaccinated with attenuated IBD vaccine and boosted with killed oil based IBDV vaccine, which conferred 90% protection. The protection of chickens injected with pRc-VP2 alone was 67% where as only 20% of the chickens in the negative control group were protected. However, enzyme-linked immunosorbent assay (ELISA) antibody titre in the group vaccinated with pRc-VP2 plus CpG ODN were significantly higher (P<0.05) than the group vaccinated with pRc-VP2 alone as well as the group vaccinated with commercial attenuated IBDV vaccine boosted with commercial oil adjuvanted killed IBDV vaccine. Responsiveness to a mitogenic lectin, phytoheamagglutinin-P was significantly reduced in group immunized with conventional vaccines (live boosted with killed) as compared to all the other groups (P<0.05). The results revealed that co-administration of recombinant plasmids with CpG ODN could protect chickens efficiently from IBDV challenge.

Adjuvants, Immunologic↗

Measurements of the absolute branching fractions of B+/- --> K+/-X(cc).

We study the two-body decays of B+/- mesons to K+/- and a charmonium state X(cc) in a sample of 210.5 fb(-1) of data from the BABAR experiment. We perform measurements of absolute branching fractions beta(B+/- --> K+/-X(cc)) using a missing mass technique, and report several new or improved results. In particular, the upper limit beta(B+/- --> K+/- X(3872)) < 3.2 x 10(-4) at 90% C.L. and the inferred lower limit beta(X(3872)J/psipi+ pi-) > 4.2% will help in understanding the nature of the recently discovered X(3872).

Journal Article↗

Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver.

AIMS/HYPOTHESIS: We used oestrogen receptor-alpha (ERalpha) knockout (ERKO) and receptor-beta (ERbeta) knockout (BERKO) mice to investigate the mechanism(s) behind the effects of oestrogens on glucose homeostasis. METHODS: Endogenous glucose production (EGP) was measured in ERKO mice using a euglycaemic-hyperinsulinaemic clamp. Insulin secretion was determined from isolated islets. In isolated muscles, glucose uptake was assayed by using radiolabelled isotopes. Genome-wide expression profiles were analysed by high-density oligonucleotide microarray assay, and the expression of the genes encoding steroyl-CoA desaturase and the Leptin receptor (Scd1 and Lepr, respectively) was confirmed by RT-PCR. RESULTS: ERKO mice had higher fasting blood glucose, plasma insulin levels and IGT. The plasma leptin level was increased, while the adiponectin concentration was decreased in ERKO mice. Levels of both glucose- and arginine-induced insulin secretion from isolated islets were similar in ERKO and wild-type mice. The euglycaemic-hyperinsulinaemic clamp revealed that suppression of EGP by increased insulin levels was blunted in ERKO mice, which suggests a pronounced hepatic insulin resistance. Microarray analysis revealed that in ERKO mice, the genes involved in hepatic lipid biosynthesis were upregulated, while genes involved in lipid transport were downregulated. Notably, hepatic Lepr expression was decreased in ERKO mice. In vitro studies showed a modest decrease in insulin-mediated glucose uptake in soleus and extensor digitorum longus (EDL) muscles of ERKO mice. BERKO mice demonstrated normal glucose tolerance and insulin release. CONCLUSIONS/INTERPRETATION: We conclude that oestrogens, acting via ERalpha, regulate glucose homeostasis mainly by modulating hepatic insulin sensitivity, which can be due to the upregulation of lipogenic genes via the suppression of Lepr expression.

Adiponectin↗

Search for lepton flavor violation in the decay tau+/--->e+/-gamma.

A search for the nonconservation of lepton flavor in the decay tau+/--->e+/-gamma has been performed with 2.07x10(8) e+e--->tau+tau- events collected by the BABAR detector at the SLAC PEP II storage ring at a center-of-mass energy near 10.58 GeV. We find no evidence for a signal and set an upper limit on the branching ratio of Beta(tau+/--->e+/-gamma)<1.1x10(-7) at 90% confidence level.

Journal Article↗

Measurement of branching fractions and resonance contributions for B0 --> D0K+pi- and search for B0 --> D0K+pi- decays.

Using 226 x 10(6) gamma(4S) --> BB events collected with the BABAR detector at the PEP-II e+e- storage ring at the Stanford Linear Accelerator Center, we measure the branching fraction for B0 --> D0K+pi-, excluding B0 --> D*-K+, to be beta(B0 --> D0K+pi-) = (88 +/- 15 +/- 9) x 10(-6). We observe B0 --> D0K*(892)0 and B0 --> D2*(2460)-K+ contributions. The ratio of branching fractions beta(B0 --> D*-K+)/beta(B0 --> D*-pi+) = (7.76 +/- 0.34+/-0.29)% is measured separately. The branching fraction for the suppressed mode B0 --> D0K+pi- is beta(B0 --> D0K+pi-) < 19 x 10(-6) at the 90% confidence level.

Journal Article↗

Presence of calcium antagonist activity explains the use of Syzygium samarangense in diarrhoea.

Syzygium samarangense (Family; Myrtaceae) or 'makopa', as it is commonly known, is native to Malaysia, some islands of Indonesia and to Far East in general. This study was undertaken to rationalize the use of this plant in hypermotility states of the gut. The hexane extract of S. samarangense (Ss.Hex) was found to dose-dependently (10-3000 microg/mL) relax the spontaneously contracting isolated rabbit jejunum. When tested for a possible calcium channel blocking (CCB) activity, the extract (10-1000 microg/mL) relaxed the high K+-induced contractions and also decreased the Ca++ dose-response curves in a dose-dependent manner (30-100 microg/mL), confirming the CCB activity. Four flavonoids isolated from the hexane extract were tested for a possible spasmolytic activity. All flavonoids, identified as: 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (SS1), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (SS2), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (SS3) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (SS4), showed dose-dependent (10-1000 microg/mL) spasmolytic activity with SS2 being the most potent. These results indicate that the presence of compounds with spasmolytic and calcium antagonist activity may be responsible for the medicinal use of the plant in diarrhoea.

Animals↗

Acute appendicitis in a kidney-pancreas transplant recipient: report of a case.

The prompt diagnosis and management of acute surgical conditions in immunocompromised solid organ transplant recipients are of critical importance. These conditions may or may not be related or to the transplanted allograft(s). This is a case report of a 41-year-old woman who received a simultaneous pancreas-kidney transplant. Nine years after the transplant, she developed acute appendicitis with a periappendiceal abscess and a fecalith, and she was treated with percutaneous drainage of the abscess and eventual semielective appendectomy. This is the first known report of acute appendicitis in a pancreas allograft recipient in the English literature.

Adult↗

Expression of glucose-6-phosphatase system genes in murine cortex and hypothalamus.

The glucose-6-phosphatase (G6Pase) system participates in the regulation of glucose homeostasis by converting glucose-6-phosphate (G6P) into glucose and inorganic phosphates. We have used an RT-PCR-based cloning and sequencing approach to study the expression of components of the G6Pase system in the hypothalamus and cortex tissues of the ob/ob mouse. We observed the expression of hepatic G6Pase catalytic subunit, G6PC, in both tissues, although increased template inputs were required for its detection. Conversely, expression of both the mouse homologue of the previously-described brain-specific G6P translocase T1 (G6PT1) variant and of the hepatic G6PT1 isoform was easily detectable in hypothalamus and cortex tissues. Of the proposed G6Pase catalytic subunit homologues, the expression of murine ubiquitous G6Pase catalytic subunit-related protein (UGRP, G6PC3) was also easily detectable in both tissues. However, islet-specific G6Pase catalytic subunit-related protein (IGRP, G6PC2) was expressed in a tissue-specific manner, and was detectable only in hypothalamus tissue at increased template inputs. We conclude that cells within ob/ob mouse hypothalamus and cortex tissues express genes with either established or proposed roles in G6P hydrolysis.

Animals↗

Urinary sex steroids during sexual development in female mice and in proximate novel males.

The experiments described here were designed to determine whether males' capacity to accelerate female pubertal development is reflected in females' urinary steroid levels in mice, and whether steroids in males' urine are influenced by exposure to developing females. In the first experiment, measures from urine collected daily from female mice aged 31-59 days showed a gradual rise in 17beta-estradiol levels and a distinct linear rise in progesterone levels. In a second experiment, daily steroids were measured in females aged 30-42 days while they were either housed alone or underneath two novel outbred males. Females exposed to males showed accelerated development at day 43 in uterine weight, and to a lesser extent in ovarian and whole-body weights. Average steroid levels did not significantly differ between conditions, but intra-individual variance in estradiol measures was greater in male-exposed than in isolated females. Creatinine levels were higher in isolated females. Males exposed to developing females excreted higher levels of estradiol in their urine compared to isolated males. These data suggest that excreted steroids can reflect general pubertal development, but may not fully reflect substantial morphological impacts of exposure to novel males. Elevations of estrogen levels in males exposed to developing females could help to account for precocious puberty in such females.

Aging↗

Effects of formalin feeding or administering into the crops of white leghorn cockerels on hematological and biochemical parameters.

Formalin administered (15 and 20 mL) into the crops of White Leghorn cockerels resulted in behavioral alterations, included depression, dullness, staggering, somnolence, anorexia, and decreased frequency of crowing. A significant decrease was observed in red blood cell counts, hemoglobin concentration, packed cell volume, and leukocyte counts in birds fed higher levels of formalin. Decreasing and increasing trends in concentrations of serum proteins and enzymes, respectively, were observed with increases in formalin doses. Significantly lower blood glucose and testosterone levels and significantly (P < 0.05) higher blood urea and creatinine concentrations were observed in birds fed higher formalin levels. No gross or microscopic lesions were observed in the birds fed different levels of formalin mixed in feed. These changes suggested that the formalin mixed in feed might have evaporated, and, hence, the amount ingested might have been too low to induce pathological changes. It was concluded from the present study that formalin mixed up to 5 mL/kg of feed, corresponding to 10 mL/bird of 3% formalin in drinking water by crop tube had no adverse effects on the health of White Leghorn cockerels.

Administration, Oral↗

Modulation of immune responses and suppression of experimental autoimmune myasthenia gravis by surgical denervation of the spleen.

Critical interactions between the nervous system and the immune system during experimental autoimmune myasthenia gravis (EAMG) were examined in an animal model for human MG after immunization of adult female Lewis rats with Torpedo acetylcholine receptor (AChR) and complete Freund's adjuvant. Immunized rats depicted marked clinical severity of the disease. Using enzyme-linked immunospot (ELISPOT) assay and in situ hybridization techniques, immune responses in these animals were examined and showed elevated numbers of anti-AChR IgG secreting B cells and AChR reactive interferon (IFN)-gamma-secreting cells, enhanced mRNA expression of the proinflammatory cytokines IFN-gamma and tumour necrosis factor (TNF)-alpha as Th1 subset and the anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as a Th2 subset, and transforming growth factor (TGF)-beta as a Th3 cytokine. Corticosterone and prostaglandin E(2) (PGE(2)) levels were measured by radioimmunoassay and illustrated increased production after immunization. Surgical denervation of the spleen reduced significantly the clinical severity of the disease, suppressed the numbers of IgG and IFN-gamma-secreting cells, down-regulated the mRNA expression for cytokines and reduced corticosterone and PGE(2) production. As controls, sham-operated rats were used and showed results as the EAMG non-denervated control rats. The data present herein, and for the first time, substantial effects of the nervous system on immune responses that may influence the outcome of EAMG. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. IL-10 and TGF-beta, the two potent immunosuppressive cytokines, were also suppressed, indicating a general suppression by splenic denervation. More investigations are initiated at our laboratories to understand the evident neural control over the immune system during challenges leading to the break of tolerance and development of autoimmunity, which may assist in innovative therapeutic approaches.

Animals↗