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Biomedical subjects

A S Khan

Publications and source records attributed to A S Khan.

At least 19 recordsLinked to original sources
PubMed2006

Plasmid-mediated growth hormone-releasing hormone efficacy in reducing disease associated with Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus infection.

The purpose of this study was to determine the effects of plasmid-mediated growth hormone releasing hormone (GHRH) supplementation on the clinical outcomes of pigs vaccinated against and challenged with either Mycoplasma hyopneumonia (M. hyo) and/or with porcine reproductive and respiratory syndrome (PRRS) virus. Before the first vaccination, pigs received a single i.m. injection of 0.625 mg of a porcine GHRH-expressing plasmid followed by electroporation of the injection site. Pigs were vaccinated at 2-wk intervals, challenged with either M. hyo and/or PRRS virus 2-wk after the second vaccination, and necropsied at 17 and 36 d after challenge. Clinical parameters associated with M. hyo challenge were improved with the GHRH treatment. Average daily gain between challenge and necropsy was improved (P = 0.04). Respiratory scores for M. hyo-challenged pigs tended to be lower in GHRH-treated animals compared to controls, and coughing scores were improved by the treatment (P = 0.01). Macroscopic lesions associated with M. hyo infection pneumonia were fewer in the group that received the GHRH-expressing plasmid. No differences between treatment groups in the macroscopic pneumonia associated with PRRS virus were observed. No differences in serum antibodies to M. hyo or PRRS virus were observed with GHRH treatment. Nevertheless, IgG in the bronchioalveolar lavage was increased by the GHRH treatment in M. hyo-challenged animals (P < 0.03). The results of this study suggest that GHRH supplementation before vaccination may enhance the protection against M. hyo-induced pneumonia and that a single dose of GHRH-expressing plasmid was sufficient to elicit an improved clinical outcome in this disease challenge model.

Animals↗
PubMed2005

Controlled cortical impact injury affects dopaminergic transmission in the rat striatum.

The therapeutic benefits of dopamine (DA) agonists after traumatic brain injury (TBI) imply a role for DA systems in mediating functional deficits post-TBI. We investigated how experimental TBI affects striatal dopamine systems using fast scan cyclic voltammetry (FSCV), western blot, and d-amphetamine-induced rotational behavior. Adult male Sprague-Dawley rats were injured by a controlled cortical impact (CCI) delivered unilaterally to the parietal cortex, or were naïve controls. Amphetamine-induced rotational behavior was assessed 10 days post-CCI. Fourteen days post-CCI, animals were anesthetized and underwent FSCV with bilateral striatal carbon fiber microelectrode placement and stimulating electrode placement in the medial forebrain bundle (MFB). Evoked DA overflow was assessed in the striatum as the MFB was electrically stimulated at 60 Hz for 10 s. In 23% of injured animals, but no naïve animals, rotation was observed with amphetamine administration. Compared with naïves, striatal evoked DA overflow was lower for injured animals in the striatum ipsilateral to injury (p < 0.05). Injured animals exhibited a decrease in V(max) (52% of naïve, p < 0.05) for DA clearance in the hemisphere ipsilateral to injury compared with naïves. Dopamine transporter (DAT) expression was proportionally decreased in the striatum ipsilateral to injury compared with naïve animals (60% of naïve, p < 0.05), despite no injury-related changes in vesicular monoamine transporter or D2 receptor expression (DRD2) in this region. Collectively, these data appear to confirm that the clinical efficacy of dopamine agonists in the treatment of TBI may be related to disruptions in the activity of subcortical dopamine systems.

Animals↗
PubMed2004

Genomics and microarray for detection and diagnostics.

Genomics provided biomedical scientists an inventory of all genes and sequences present in a living being. This provides an unique opportunity to the scientists to predict and study biological functions of these genes. The changes in the gene expression regulated by genomic sequences therefore reflect changes in the molecular processes working in a cell or tissue in response to external factors including exposure to toxic compounds and pathogens. Microarray offers a biotechnological revolution with the help of DNA chemistry, silicon chip technology and optics to be used to monitor gene expression for thousands of genes in one single experiment. Briefly, 20,000 to 100,000 unique DNA molecules get applied by a robot to the surface of silicon wafers (approximately the size of a microscope slide). Using a single microarray experiment, the expression level of 20,000 to 100,000 genes will be examined in one single experiment. Genomics and microarray have a significant role and impact on the design and development of modern detection and diagnostic tools in several different ways. Microarray tools are now used on regular basis for monitoring gene expression of large number of genes and also frequently applied to DNA sequence analysis, immunology, genotyping, and molecular diagnosing. For diagnostics, these tools can be used to distinguish and differentiate between different DNA fragments that differ by as little as a single nucleotide polymorphism (SNP). These microarrays can be divided based on the gene density spots that will be high density (>10,000 spots) per slide, medium (< 1000 > 100) and low density (< 100). High-density arrays have proven to be very useful in disease diagnosis especially in diagnosis and classification of different types of cancers. These microarray tools hold tremendous potential for pathogen detection, which will be comprised, of unique sets of genes (also referred to as "signatures") able to unambiguously identify the species and strain of pathogens of interest.

Drug Design↗
PubMed2003

Effects of plasmid-mediated growth hormone releasing hormone supplementation in young, healthy Beagle dogs.

Our study focused on the evaluation of the pharmacological and toxicological effects of plasmid-mediated GHRH supplementation with electroporation in normal adult dogs over a 180-d period. Twenty-eight dogs (< 2 yr of age) were randomized to four groups. Three groups (four dogs/sex for each group) were treated with ascending doses of GHRH-expressing plasmid: 0.2, 0.6, and 1 mg. One group (two dogs of each sex) served as the control. Clinical observations and body weights were recorded. Hematological, serum biochemical, and urine analyses were performed. Serum IGF-I, ACTH, and insulin were determined. Necropsies were performed on d 93 and 180; organs were weighed and tissues were fixed and processed for light microscopy. Selected tissues were used to assess plasmid biodistribution on d 93. At all doses, plasmid GHRH caused increased weight gain (P < 0.001), without organomegaly. Serum glucose and insulin in fasted dogs remained within normal ranges at all time points. Adrenocorticotropic hormone was normal in all groups. Significant increases in number of red blood cells, hematocrit, and hemoglobin (P < 0.01) were observed. In conclusion, our study shows that plasmid-mediated GHRH supplementation is safe in electroporated doses up to 1.0 mg in young healthy dogs.

Adrenocorticotropic Hormone↗
PubMed2003

Hantaviruses: a tale of two hemispheres.

Infectious febrile nephropathies, initially described as epidemics during military campaigns in Europe and Asia at the turn of the 20(th) century, were eventually all unified under the rubric of hemorrhagic fever with renal syndrome (HFRS) and ascribed to infection from rodent-borne hantaviruses. At the end of the century, hantavirus pulmonary syndrome (HPS) was described throughout the Americas as a consequence of infection with the New World hantaviruses. The epidemiology and clinical manifestations of these diseases are linked to the ecology of their associated rodent hosts. Murine rodents (Old World mice and rats) are associated with the severe forms of HFRS in Asia and the Balkans due to Hantaan, Dobrava, and Seoul viruses. Hantaan virus causes an estimated 50-100,000 infections a year in China alone. Arvicoline rodents (voles) are associated with a mild form of HFRS in Europe called nephropathia epidemica due to Puumala virus. Sigmodontine rodents (New World rats and mice) are associated with approximately 200 HPS cases per year throughout the Americas caused by over a dozen viruses. The viruses are mainly transmitted as small-particle aerosols of rodent excreta, and the subsequent infections share cardiovascular shock as a prominent feature, although HFRS causes predominantly renal disease, while HPS causes a predominantly non-cardiogenic pulmonary edema - hemorrhage involvement varies in the syndromes on the basis of virus subtypes. Efforts are underway to refine prevention strategies, understand the pathogenesis of the shock, and identify therapeutic modalities.

Animals↗
PubMed2002

Superstitions regarding health problems in different ethnic groups in Karachi.

OBJECTIVE: To find out the superstitions regarding health problems in different ethnic groups, their implications over the socio-economic development of that group and to what extent can those superstitions be related to their level of literacy. METHODS: The study was a questionnaire-based survey, 20 subjects from each ethnic group were selected by cluster sampling of residential areas where that particular group has its highest concentration, making a total of 100 subjects. RESULTS: It was found that most people (73%) do have some superstitious beliefs. Fifty percent of people believe in them as a part of culture and tradition, another 25% got them from their elders. No significant difference was found between different racial groups (p value = 0.9). According to literacy rate, 73.5% of literate community and 94.1% illiterate community were found to have superstitions. The occupation of the breadwinner of family didn't have a significant impact over the belief in superstitions (p value = 0.6). CONCLUSION: Majority of our population believes in superstitions, which are more common in illiterates. These superstitions not only predict health seeking behaviour of a person but also play a major role in shaping the response of a community to any health intervention program. Without the knowledge of these superstitions, effective community participation cannot be achieved.

Adolescent↗
PubMed2002

Prevalence of depression in patients with coronary artery disease in a tertiary care hospital in Pakistan.

OBJECTIVE: To determine the prevalence of depression in patients with coronary artery disease (CAD) in a tertiary care hospital setting in Pakistan. METHODS: One hundred and fifty four patients of CAD (115 males and 39 females) were randomly selected from the outpatient department and wards of the National Institute of Cardiovascular Diseases, Karachi and were scored for depression via the Hospital Anxiety and Depression Scale. Basic demographic data and disease variables were also collected. RESULTS: The point prevalence of depression in the sample was 37% (31.3% males and 53.8% females). Female sex, income level below Rs. 5000 per month, low education level, outpatient, single earning family member and hypertension were few variables associated positively with depression (p < 0.05). Only one patient was receiving treatment for depression by his cardiologist. CONCLUSION: Depression is prevalent in CAD patients in Pakistan. Economic conditions may pose an additional threat on these patients. Treating physicians (especially cardiologists) need to be aware of this co-morbidity so as to be able to diagnose and adequately manage such patients.

Adult↗
PubMed2001

Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome.

To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups.

Antiviral Agents↗
PubMed2001

Early detection of endogenous retroviruses in chemically induced mouse cells.

Endogenous retroviral sequences are present as an integral part of eukaryotic genomes. Although the majority of these sequences are defective, a few can produce infectious virus, either spontaneously upon long-term culture or by treatment with various chemical or other agents. Early, extensive studies of retrovirus induction were done in mouse cells; however, similar studies have not been done using state-of-the-art virus detection assays and with cells of other mammalian species. To investigate induction and detection of occult retroviruses in cells of different species, especially primate cells that are used in production of biologics, we have initially determined the optimum conditions for retrovirus induction in chemically treated K-BALB mouse cells using highly sensitive product-enhanced reverse transcriptase (PERT) assays as well as transmission electron microscopy (TEM). Retrovirus induction was detected at day 1 post-drug treatment under all test conditions but was optimum using 30 microg ml(-1) of 5-iododeoxyuridine (IdU) for 24 h. Additionally, the combination of IdU and 5-azacytidine specifically enhanced activation of type C particles. RT activity was detected by PERT assays in one microliter equivalent of test sample and retroviral particle production was seen by TEM analysis. The induction of infectious murine leukemia retroviruses was confirmed by infectivity assays and correlated with PERT activity. These results indicate that strategies for detection of occult viral agents should include optimization of induction conditions using multiple viral detection assays to evaluate virus activation.

3T3 Cells↗
PubMed2001

IL-15-induced conversion of monocytes to mature dendritic cells.

IL-15 is produced by a wide variety of tissues in response to inflammatory stimuli. We examined the effect of IL-15 in supporting the maturation of monocytes to dendritic cells in ex vivo culture. IL-15 transformed CD14(+) monocytes to mature dendritic cells. These dendritic cells were similar to those obtained from monocyte cultures treated with a combination of the cytokines GM-CSF, IL-4 and TNF-alpha. The effects of IL-15 did not depend on endogenously produced GM-CSF. The IL-15-induced dendritic cells also expressed chemokines and stimulated strong allo-responses that were characteristic of mature dendritic cells. These data indicate that CD14(+) monocytes respond to IL-15 by undergoing morphological transformation and acquiring characteristic dendritic cell features that facilitate antigen-specific responses of T cells. Thus, the release of IL-15 by inflammatory stimuli may induce the conversion of monocytes to immuno-stimulatory dendritic cells to support primary immune responses against pathogens.

Antigens, CD↗
PubMed2001

Hantavirus pulmonary syndrome in the State of São Paulo, Brazil, 1993-1998.

Between 1993 and 1998, 10 cases of clinical hantavirus infection were diagnosed in Brazil. Hantavirus-specific IgM, or positive immunohistochemical analysis for hantavirus antigen, or positive reverse transcription-polymerase chain reaction results for hantavirus RNA were used to confirm nine of these cases; eight were hantavirus pulmonary syndrome (HPS), and one was mild hantavirus disease. The remaining clinical case of hantavirus infection was fatal, and no tissue was available to confirm the diagnosis. During the first 7 months of 1998, five fatal HPS cases caused by a Sin Nombre-like virus were reported from three different regions in the State of São Paulo, Brazil: two in March (Presidente Prudente Region), two in May (Ribeirão Preto Region), and one in July (Itapecerica da Serra Region). Epidemiologic, ecologic, and serologic surveys were conducted among case contacts, area residents, and captured rodents in five locations within the State of São Paulo in June of 1998. Six (4.8%) of 125 case contacts and six (5.2%) of 116 area residents had IgG antibody to Sin Nombre virus (SNV) antigen. No case contacts had a history of HPS-compatible illness, and only one area resident reported a previous acute respiratory illness. A total of 403 rodents were captured during 9 nights of trapping (1969 trap nights). All 27 rodents that were found to be positive for IgG antibody to SNV antigen were captured in crop border and extensively deforested agricultural areas where four of the 1998 HPS case-patients had recently worked. The IgG antibody prevalence data for rodents suggest that Bolomys lasiurus and perhaps Akodon sp. are potential hantavirus reservoirs in this state of Brazil.

Adolescent↗
PubMed2001

Growth hormone increases regional coronary blood flow and capillary density in aged rats.

In this study, we examined the effects of age and growth hormone replacement on both coronary blood flow and capillary density. Blood flow was measured by using [(14)C]-iodoantipyrine in three groups of anesthetized Brown Norway x Fischer 344 rats: young vehicle-treated animals (6 months; n = 13), old vehicle treated animals (30 months; n = 9), and old animals treated with bovine growth hormone (200 microg/kg) twice a day for 30 days (30 months; n = 7). Capillary density was measured by color segmentation analysis of sections stained for platelet endothelial cell adhesion molecule-1. In all regions examined, coronary blood flow decreased with age, and growth hormone administration resulted in an increase in flow compared to vehicle-treated animals. Capillary density decreased with age in the apex and the left ventricular middle segment. In response to growth hormone administration, capillary density increased significantly in the apex but not in other regions of the heart. Our results demonstrate that growth hormone enhances regional myocardial blood flow in the aged heart and suggest that part of this effect could be due to an increase in capillary density.

Aging↗
PubMed2001

Hantavirus pulmonary syndrome: at the crossroads.

The initial identification in 1993 of hantavirus pulmonary syndrome as a novel, highly fatal respiratory illness among American Indians in the southwestern USA in 1993 opened the window to the recognition of a well-established pan-American zoonosis with a myriad of causative viruses and rodent vectors, although all are New World hantaviruses among New World sigmodontine rodents. The clinical spectrum of symptoms has also been expanded to include asymptomatic infection through to fulminant hemorrhagic fever. Although the use of ribavirin, an antiviral drug, was disappointing in an early, open-labeled trial, early detection and supportive care is much better refined. However, much work remains in probing the pathogenesis of this syndrome to help define and explore therapeutic options and the mechanism of person-to-person transmission with Andes virus, one of the viruses that cause hantavirus pulmonary syndrome. Current remote sensing efforts and longitudinal ecologic investigations need to be expanded in order to focus prevention efforts better.

Animals↗
PubMed2001

Novel type of fimbriae encoded by the large plasmid of sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H(-).

Sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:H(-) have emerged as important causes of diarrheal diseases and the hemolytic-uremic syndrome in Germany. In this study, we characterized a 32-kb fragment of the plasmid of SF EHEC O157:H(-), pSFO157, which differs markedly from plasmid pO157 of classical non-sorbitol-fermenting EHEC O157:H7. We found a cluster of six genes, termed sfpA, sfpH, sfpC, sfpD, sfpJ, and sfpG, which mediate mannose-resistant hemagglutination and the expression of fimbriae. sfp genes are similar to the pap genes, encoding P-fimbriae of uropathogenic E. coli, but the sfp cluster lacks homologues of genes encoding subunits of a tip fibrillum as well as regulatory genes. The major pilin, SfpA, despite its similarity to PapA, does not cluster together with known PapA alleles in a phylogenetic tree but is structurally related to the PmpA pilin of Proteus mirabilis. The putative adhesin gene sfpG, responsible for the hemagglutination phenotype, shows significant homology neither to papG nor to other known sequences. Sfp fimbriae are 3 to 5 nm in diameter, in contrast to P-fimbriae, which are 7 nm in diameter. PCR analyses showed that the sfp gene cluster is a characteristic of SF EHEC O157:H(-) strains and is not present in other EHEC isolates, diarrheagenic E. coli, or other Enterobacteriaceae. The sfp gene cluster is flanked by two blocks of insertion sequences and an origin of plasmid replication, indicating that horizontal gene transfer may have contributed to the presence of Sfp fimbriae in SF EHEC O157:H(-).

Amino Acid Sequence↗
PubMed2001

No evidence of infectious retroviruses in measles virus vaccines produced in chicken embryo cell cultures.

All vaccines that are prepared in chicken embryo fibroblasts (CEFs) contain a low level of particle-associated reverse transcriptase (RT) activity, which is produced from the avian cell substrate. The RNAs present in the particles have sequence homology to viral DNAs belonging to the ancient endogenous avian virus (EAV) family or to the avian sarcoma-leukosis virus (ALV)-related subgroup E endogenous virus loci. Although no replication-competent retrovirus has been associated with the RT activity produced from CEFs, there have been some theoretical safety concerns regarding potential consequences of integration of EAV and ALV sequences in human DNA, which may result from nonproductive infection with replication-defective particles or infection with EAV and ALV pseudotypes bearing measles virus envelopes. To address these possibilities, we have analyzed EAV and ALV particles in a measles virus vaccine equivalent (MVVE) preparation, obtained from a U.S. manufacturer, for integration and for replication in human peripheral blood mononuclear cells (PBMCs). The results show the absence of EAV and ALV integrants in DNA prepared from MVVE-inoculated human cells by direct DNA PCR and Alu PCR assays and no propagation of retrovirus in 18-day cultures of MVVE-inoculated human PBMCs by a highly sensitive PCR-based RT assay. These results provide further confidence regarding the safety of chicken RT activity in live viral vaccines and support the continued use of chick-cell-derived vaccines in humans.

Alpharetrovirus↗
PubMed2001

Growth hormone reverses age-related cardiac myofilament dysfunction in rats.

We tested the hypotheses that aging is associated with a reduction in overall cardiac contractility and myofilament force generation that could be reversed with growth hormone (GH) replacement. Three groups of male Brown-Norway rats were studied: young (Y(SAL): 8 mo old, n = 13), old (O(SAL): 28 mo old, n = 13), and old GH-treated (O(GH): 28 mo old, n = 12; 300 microg bovine GH, twice a day for 30 days). The left ventricular (LV) pressure-volume relation was derived in isolated hearts, after which isolated trabecular muscles from these hearts were permeabilized and maximal myofilament force generation (Fmax) was measured. LV developed pressures at a LV volume of 0.3 ml were significantly depressed with age: 84 +/- 6 vs. 71 +/- 6 mmHg (Y(SAL) vs. O(SAL), respectively, P = 0.001) and not restored by GH (69 +/- 4 mmHg). Fmax was reduced in the aged hearts: 47.5 +/- 3.12 vs. 35.9 +/- 3.03 mN/mm2 (Y(SAL) vs. O(SAL), respectively, P = 0.014) but was restored with GH replacement to 46.7 +/- 3.12 mN/mm2 (O(SAL) vs. O(GH), P = 0.021). Our results suggest that cellular myofilament contractility is reduced with aging and restored with GH replacement.

Aging↗
PubMed2001

Pert analysis of endogenous retroviruses induced from K-BALB mouse cells treated with 5-iododeoxyuridine: a potential strategy for detection of inducible retroviruses from vaccine cell substrates.

The activation of an endogenous, infectious retrovirus in a cell substrate that is used for the production of biologics is an important safety concern, especially in the case of live, viral vaccines, where there are minimal purification and inactivation steps in order to preserve high vaccine potency. Extensive analysis has been done to evaluate various chemical agents for the induction of endogenous retroviruses in murine and avian cells; however, similar studies have not been done with cells of other species, especially human and non-human primates, that are used in vaccine production. To develop a strategy for optimal induction and sensitive detection of endogenous, infectious retroviruses in currently used or potential vaccine cell substrates, we have initially investigated the use of a state-of-the-art, highly-sensitive, product-enhanced reverse transcriptase (PERT) assay for evaluating the kinetics of retrovirus induction and replication in 5-iododeoxyuridine (IdU)-treated K-BALB mouse cells, where endogenous retrovirus activation has previously been described. In general, the overall kinetics of virus production were similar to those of previous studies in that two peaks of RT activity were seen on long-term culture of IdU-treated K-BALB cells; however, retrovirus activation was detected earlier under our induction conditions and with greater sensitivity using the PERT assay, where 1-10 virions were detected in 1 microl equivalent of the test sample, without concentration. Furthermore, the PERT activity corresponded to the presence of infectious, murine leukaemia viruses (MuLVs) induced from K-BALB cells. Based upon these results, a strategy is proposed using the PERT assay for detection of inducible, endogenous retroviruses in vaccine cell substrates.

3T3 Cells↗