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Biomedical subjects

M Malek

Publications and source records attributed to M Malek.

At least 19 recordsLinked to original sources

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗

Effect of social deprivation on mortality and the duration of hospital stay after a stroke.

BACKGROUND: We aim to assess whether social deprivation independently predicts case fatality after a stroke patient has been admitted to hospital, and to assess whether social deprivation affected duration of hospital stay. METHODS: Cohort study in a tertiary teaching hospital included consecutive patients admitted to hospital within 48 h of their stroke between 1988 and 1994. Outcome measures were case fatality at 1 year and length of hospital stay. The socioeconomic category was derived from the postcode sector of residence for the patients (Carstairs index). Cause of death was determined by data linkage to the Registrar General data for Scotland. RESULTS: 2,042 stroke patients were included. A significant age difference existed between the deprivation categories (76.0 +/- 10.9 years in the affluent cohort vs. 71.4 +/- 10.7 years in the deprived cohort). Smoking was more common in the deprived group. ECG findings and neurological score on admission were similar between the groups. No difference existed between groups for length of hospital stay (p = 0.793), and in the proportions remaining alive at 1 year (p = 0.416). When entered into a multivariate Cox regression analysis, the deprivation categories did not predict mortality. Age, sex, Philadelphia Geriatric Center Instrumental Activities of Daily Living (IADL) Scale Score, Orgogozo neurological score on admission, and ECG abnormalities were the significant predictors. CONCLUSIONS: Stroke patients living in more socially deprived areas had their strokes at an earlier age but were not at a greater risk of dying or longer hospital stay once they had been admitted to hospital.

Aged↗

[Acute hepatitis due to kava-kava and St John's Wort: an immune-mediated mechanism?].

HISTORY AND CLINICAL FINDINGS: In an otherwise healthy 48-year-old female patient, acute hepatitis with transaminase increase (GOT up to 613 U/l, GPT up to 752 U/l), inconspicuous hepatitis serology findings, negative autoantibody status and negative virus serology was observed after a 10-week long intake of kava-kava (1-3 x 200 mg/day) and St John's Wort (1 x 425 mg/day). Biopsy of the liver showed lobular and portal necroinflammatory activity without indication of cirrhosis. DIAGNOSIS: Due to these findings with proven T-cell activity (lymphocyte typing, neopterin determination) as well as the aetiopathology, this form of hepatitis with histological characteristics of a nutritive/medicinal toxic origin was classified as induced immunologic idiosyncratic hepatitis, possibly in terms of an antibody-negative autoimmune hepatitis. TREATMENT AND CLINICAL COURSE: Discontinuation of the existing medication and simultaneous onset of immunosuppressive combination therapy of cortisone, azathioprine and ursodeoxycholic acid resulted in normalisation of the liver parameters within a period of two months. CONCLUSION: On the one hand, it appears that simultaneous intake of St John's Wort possibly potentiates the toxicity of kavapyrones. On the other hand, an immune-mediated mechanism, induced by kava-kava, cannot be completely excluded in the present case. It must be stressed that in patients with autoimmune hepatitis, precise history of medication intake should also be available.

Alanine Transaminase↗

Radiation hybrid mapping of 18 positional and physiological candidate genes for arthrogryposis multiplex congenita on porcine chromosome 5.

We report the chromosomal assignment of 18 porcine genes to human homologues using the INRA-Minnesota swine radiation hybrid panel (IMpRH). These genes (CACNA1C, COL2A1, CPNE8, C3F, C12ORF4, DDX11, GDF11, HOXC8, KCNA1, MDS028, TMEM106C, NR4A1, PHB2, PRICKLE1, Q6ZUQ4, SCN8A, TUBA8 and USP18) are located on porcine chromosome 5 (SSC5) and represent positional and functional candidates for arthrogryposis multiplex congenita (AMC), which maps to SSC5. CPNE8, PRICKLE1, Q6ZUQ4 and TUBA8 were mapped to the interval for pig AMC between microsatellites SW152 and SW904. Three SNPs in TUBA8 co-segregated with the AMC phenotype in 230 pigs of our research population without recombination and could be used as a genetic marker test for AMC. In addition, we provide evidence that a small chromosomal region of HSA22q11.2 evolutionarily corresponds to SSC5q12-q22 (and contains the human homologues of porcine SW152, Q6ZUQ4, TUBA8 and USP18), while the regions flanking HSA22q11.2 on SSC5 correspond to HSA12p13 and HSA12q12. We identified seven distinct chromosomal blocks, further supporting extensive rearrangements between genes on HSA12 and HSA22 in the AMC region on SSC5.

Animals↗

Association of Helicobacter pylori infection with cardiac syndrome X.

INTRODUCTION: Cardiac syndrome X (CSX) includes chest pain, positive exercise stress test and/or radionuclide test for ischaemia and normal coronary angiography. There is no obvious aetiology for this syndrome. Some mechanisms such as endothelial dysfunction and oestrogen deficiency have been invoked. In this study, we surveyed the association of Helicobacter pylori (HP) infection with cardiac syndrome X. METHODS: HP infection was detected by urea breath test (UBT) in patients with cardiac syndrome X, and compared with a sex- and age-matched control group. Patients with dyspepsia and coronary spasm were excluded. Statistical analysis was carried out using chi-square test. RESULTS: 40 patients (29 females and 11 males) with cardiac syndrome X aged between 30 and 65 years (mean 45.51 +/- 5.03 years) were compared with a control group (28 females and 12 males) aged between 31 and 64 years old (mean 44.93 +/- 5.16 years). 95 percent of patients were HP infected, while only 47.5 percent of members of the control group were infected (p-value is less than 0.001). CONCLUSION: Considering the high prevalence of HP infection in patients with CSX in our sample and probable causative effect of chronic infection in vascular diseases, we believe that there is a probable role for HP infection in the pathogenesis of CSX.

Adult↗

Application of bovine microsatellite markers for genetic diversity analysis of Swiss yak (Poephagus grunniens).

In order to assess the applicability of bovine microsatellite markers for population genetic studies in Swiss yak, 131 bovine microsatellite markers were tested on a panel of 10 animals. Efficient amplification was observed for 124 markers (94.6%) with a total of 476 alleles, of which 117 markers (94.3%) were polymorphic. The number of alleles per locus among the polymorphic markers ranged from two to nine. Seven loci (ILSTS005, BMS424B, BMS1825, BMS672, BM1314, ETH123 and BM6017) failed to amplify yak genomic DNA. Two cattle Y-chromosome specific microsatellite markers (INRA126 and BM861) amplified genomic DNA from both male and female yaks. However, two additional markers on cattle Y-chromosome (INRA124 and INRA189) amplified DNA from only males. Of the polymorphic markers, 24 microsatellites proposed by CaDBase for within- and cross-species comparisons and two additional highly polymorphic markers (MHCII and TGLA73) were used to investigate the genetic variability and the population structure of a Swiss yak herd that included 51 additional animals. The polymorphic information content ranged from 0.355 to 0.752, while observed heterozygosity (HO) ranged from 0.348 to 0.823. Furthermore, a set of 13 markers, organized into three multiplex polymerase chain reactions, was evaluated for routine parentage testing. This set provided an exclusion probability in a family of four yaks (both parents and two offspring) of 0.995. These microsatellites serve as useful tools for genetic characterization of the yak, which continues to be an important domestic livestock species.

Animals↗

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗

Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.

A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)</=(3.6x10(-10))micro(B) at 90% C.L. by fitting to the Super-Kamiokande day-night spectra. The fitting took into account the effect of neutrino oscillation on the shapes of energy spectra. With additional information from other solar neutrino and KamLAND experiments constraining the oscillation region, a limit of micro(nu)</=(1.1x10(-10))micro(B) at 90% C.L. was obtained.

Journal Article↗

Analysis of chicken TLR4, CD28, MIF, MD-2, and LITAF genes in a Salmonella enteritidis resource population.

Salmonella enteritidis is a foodborne pathogen that negatively affects both animal and human health. Genetic variations in response to pathogenic SE colonization or to SE vaccination were measured in a chicken resource population. Outbred broiler sires and 3 diverse, highly inbred dam lines produced 508 F1 progeny that were evaluated for either bacterial colonization after pathogenic SE inoculation or circulating antibody level after SE vaccination. Five candidate genes were selected for study, based on their biological function as possibly affecting response to SE: toll-like receptor 4 (TLR4), T-cell specific surface protein (CD28), macrophage migration inhibitory factor (MIF), MD-2, and lipopolysaccharide-induced tumor necrosis factor (TNF)-alpha factor (LITAF). Gene fragments were sequenced from the founder lines of the resource population. The LITAF and MIF genes were homozygous for all sires. Single nucleotide polymorphisms (SNP) were identified in 3 genes (TLR4, CD28, and MD-2) and were used to test for associations of sire SNP with SE response. Linear mixed models were used for statistical analyses. The CD28 broiler sire SNP was associated with both bacterial load in the cecum (P < 0.003) and vaccine antibody response (P < 0.05). The MD-2 SNP was associated (P < 0.04) with the bacterial load in the spleen. The use of these SNP in these genes in marker-assisted selection may result in enhancement of disease resistance.

Animals↗

Genetics of osteochondral disease and its relationship with meat quality and quantity, growth, and feed conversion traits in pigs.

The main objective of this research was to estimate heritabilities of seven osteochondrosis (OC) lesions in station-tested pigs and their genetic and phenotypic correlations with four meat quality (MQ) traits, the percentage of premium cuts (PPC), daily weight gain (DWG), and feed conversion ratio (FCR). Observed OC lesions were on the head of humerus (HK), condylus medialis humeri (CMH), condylus lateralis humeri (CLH), radius and ulna proximal (RUP), distal epiphyseal cartilage of ulna (DEU), head of femur (FK), and condylus medialis femoris (CMF). Meat quality traits were i.m. fat (IMF), muscle pH at 1 h after slaughter (pH1), muscle pH at 30 h after slaughter (pH30), and light reflectance on muscle (H30). The data set comprised 2,710 animals, of which 1,291 animals had OC records. All traits were analyzed by multiple-trait linear mixed model, with the animal's genetic and common litter effects as random. Fixed effects in the model varied between traits. Each OC lesion was further analyzed by a univariate generalized linear mixed model or, equivalently, "threshold models," assuming logistic, probit (normal), and Poisson distributions of the underlying "liability" to the disease. For OC lesions, estimates of heritability were low on the original "incidence" scale (0.06 for HK to 0.16 for CLH) and moderate to high on the liability scale (0.08 to 0.42). Genetic correlations (r(g)) between OC lesions and most MQ traits and PPC were generally unfavorable. Significant r(g) were -0.44 for DWG-CMH, 0.31 for DWG-CMF, 0.40 for FCR-HK, 0.21 for PPC-CLH, 0.32 for PPC-RUP, 0.30 for PPC-CMF, -0.54 for pH1-CLH, 0.47 for pH1-DEU, -0.34 for pH30-CMH, 0.58 for pH30-DEU, -0.50 for H30-HK, -0.31 for H30-DEU, and 0.31 for H30-CMF. Genetic susceptibilities to some OC lesions within the front leg were positively related to each other (r(g) range = 0.57 to 0.69), but r(g) between front and hind leg OC lesions were mostly negative (range = -0.21 to -0.40). Estimated h2 was 0.60 for PPC, and ranged from 0.12 to 0.66 for MQ traits, 0.28 for DWG, and 0.42 for FCR. Genetic correlations among meat quality and quantity traits ranged from -0.66 to 0.37. This is the first study to report genetic and phenotypic correlations between OC lesions and several meat quality and quantity traits in pigs. These findings will be useful to pig industry, especially in designing breeding programs for robust pigs.

Aging↗

Characterization of quantitative trait loci for growth and meat quality in a cross between commercial breeds of swine.

A three-generation resource family was created by crossing two Berkshire grandsires with nine Yorkshire granddams to identify QTL affecting growth, body composition, and meat quality. A total of 512 F2 offspring were evaluated for 11 traits related to growth and body composition and 28 traits related to meat quality. All animals were initially genotyped for 125 markers across the genome. The objectives of this advanced phase of the project were to further identify and characterize QTL after genotyping for another 33 markers in special regions of interest, and to develop and apply methods for detecting QTL with parent-of-origin effects. New marker linkage maps were derived and used in QTL analysis based on line-cross least squares regression-interval mapping. A decision tree for identifying QTL with parent-of-origin effects was developed based on tests against the Mendelian mode of expression. Empirical significance thresholds were derived at chromosomewise and genomewise levels using specialized permutation strategies to create data under the null hypothesis appropriate for each test. Significance thresholds derived by the permutation tests were validated based on simulation of a pedigree and data structure similar to the Berkshire-Yorkshire population. The addition of 33 markers resulted in the discovery of 29 new QTL at the 5% chromosomewise level using the Mendelian model of analysis. Thirteen of the original QTL were no longer significant at the 5% chromosomewise level. A total of 33 QTL with parent-of-origin effects were identified, including QTL with paternal expression for backfat and loin muscle area on chromosome 2, near IGF2, and QTL with maternal expression for drip loss and reflectance on chromosome 9. Tests for imprinting against Mendelian expression identified much fewer QTL with parent-of-origin effects than tests based on significance of paternal and maternal alleles, which have been used in other studies. The detected QTL and their identified mode of expression will allow further research in these QTL regions and their utilization in marker-assisted improvement of meat quality.

Adipose Tissue↗

Search for nu(e) from the sun at Super-Kamiokande-I.

We present the results of a search for low energy nu(e) from the Sun using 1496 days of data from Super-Kamiokande-I. We observe no significant excess of events and set an upper limit for the conversion probability to nu(e) of the 8B solar neutrino. This conversion limit is 0.8% (90% C.L.) of the standard solar model's neutrino flux for total energy=8-20 MeV. We also set a flux limit for monochromatic nu(e) for E(nu(e))=10-17 MeV.

Journal Article↗

Amifostine plus erythropoietin in a patient with low-risk myelodysplastic syndrome.

Increasingly, the therapeutic use of hematopoietic growth factors and immunomodulatory agents is under investigation in patients with low-risk myelodysplastic syndrome (MDS). Studies on amifostine therapy-alone or in combination with erythropoietin (EPO)-indicate that long-term treatment is possibly a decisive factor for therapy success. Therefore, we treated an 81-year-old female, transfusion-dependent patient with MDS and refractory anemia (RA) with amifostine and EPO over a period of 2 years. Following a 4-week induction phase of 5 x 500 mg amifostine plus 3 x 10000 IU EPO per week and maintenance therapy of 1 x 500 mg amifostine plus 3 x 10000 IU EPO per week, normal hemoglobin values were reached in week 14. A long-lasting erythroid response could be observed with a reduction of EPO to 2 x 10000 IU and 1 x 10000 IU and, at present, once a week application of amifostine alone (1 x 500 mg). Apart from the 1st week, the treatment was carried out at the outpatient department and was well tolerated by the patient. The patient experienced a good general clinical condition without further need for hospitalization or blood transfusions.

Aged↗

Search for supernova relic neutrinos at Super-Kamiokande.

A search for the relic neutrinos from all past core-collapse supernovae was conducted using 1496 days of data from the Super-Kamiokande detector. This analysis looked for electron-type antineutrinos that had produced a positron with an energy greater than 18 MeV. In the absence of a signal, 90% C.L. upper limits on the total flux were set for several theoretical models; these limits ranged from 20 to 130 macro nu(e) cm(-2) s(-1). Additionally, an upper bound of 1.2 macro nu(e) cm(-2) s(-1) was set for the supernova relic neutrino flux in the energy region E(nu)>19.3 MeV.

Journal Article↗

Association of twelve candidate gene polymorphisms and response to challenge with Salmonella enteritidis in poultry.

Breeding for disease resistance to Salmonella enteritidis (SE) could be an effective approach to control Salmonella in poultry. The candidate gene approach is a useful method to investigate genes that are involved in genetic resistance. In this study, 12 candidate genes that are involved in the pathogenesis of Salmonella infection were investigated using five different genetic groups of meat-type chicken. The genes were natural resistance associated macrophage protein 1 (SLC11A1, previously known as NRAMP1), inhibitor of apoptosis protein 1 (IAP1), prosaposin (PSAP), Caspase-1 (CASP1), inducible nitric oxide production (iNOS), interferon-gamma (IFNG), interleukin-2 (IL2), immunoglobulin light chain (IGL), ZOV3, and transforming growth factors B2, B3 and B4 (TGFB2, B3 and B4). In total, 117 birds of all groups were challenged with SE at the age of 3 weeks. In all birds at 7-day post-infection SE load in caecum content, spleen and liver were quantified. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays were used to genotype all animals for each gene. Overall we found the most significant associations with caecum content, nine of 12 genes showed a significant association (SLC11A1, IAP1, PSAP, CASP1, iNOS, IL2, IGL, TGFB2 and TGFB4). For liver, five genes (SLC11A1, CASP1, IL2, IGL, and TGFB4) and for spleen, only one gene (TGFB3) showed a significant association with SE load. By showing associations of 12 PCR-RFLP assays with SE load after a pathogen challenge, this study confirmed the polygenic nature of disease resistance to SE.

Animals↗

[Severe exacerbation of chronic hepatitis B during therapy with corticosteroids and lamivudine therapy and successful short-term combination therapy with interferon-beta and interferon-gamma].

Following an acute episode of undifferentiated collagenosis/autoimmune disease with joint pain, a 50-year-old female patient with known long-standing chronic hepatitis B was treated orally with corticosteroids (30 mg prednisolone in decreasing doses over a period of six months). During this treatment, exacerbation of hepatitis B and massive flare-up under simultaneous treatment with lamivudine occurred (GOT 530 U/L, GPT 791 U/L). Serology was positive for HBs-Ag and anti-HBc-lgM. HBV-DNA titer was > 400,000 copies/ml in polymerase chain reaction. Considering the increased risk of reactivation of autoimmune phenomena during a six months therapy with interferon-alpha, an intensive combination therapy with interferon-beta and -gamma (2 weeks: 1 x 3 MIU nIFN-beta Fiblaferon i.v.; 3 weeks: 1 x 3 MIU nIFN-beta i.v. plus 1 x 50 microg rIFN-gamma Imukine) was carried out over five weeks. After two months this resulted in a complete viral and biochemical response. During an observation period of twelve months no reactivation of the autoimmune disease occurred.

Anti-Inflammatory Agents↗

Intrapericardial instillation of mitoxantrone in palliative therapy of malignant pericardial effusion.

BACKGROUND: Pericardial effusions occurring with pericardial or myocardial metastases often cause serious complications, necessitating temporary or emergency relief by percutaneous pericardiocentesis. However, this often results in recurrences. For long-term therapy success, the intrapericardial instillation of anti-neoplastic agents is an alternative to surgical methods, which are stressful for the patient. Following our positive experiences with mitoxantrone in the treatment of malignant pleural effusions, we applied this substance for the therapy of malignant pericardial effusions. PATIENTS AND METHODS: 16 patients with cytologically verified malignant pericardial effusions (8 with bronchial carcinoma, 7 with carcinoma of the breast, 1 with adenocarcinoma of the stomach) received an intrapericardial instillation of mitoxantrone 1-3 x10-20 mg. Responses were evaluated by echocardiography 30 days after completion of therapy. RESULTS: 12 of 16 patients showed complete remission (no recurrence of a detectable effusion). 3 patients showed a partial remission (recurrence of non-drainage-dependent effusion) (CR + PR = 94%). Within the mean follow-up period of 189 days no recurrences occurred. The rate of side effects was low. CONCLUSION: Intrapericardial instillation of mitoxantrone is a feasible and effective palliative method for the control of malignant pericardial effusions with little strain on the patients, short duration of hospital stay, cytotoxic characteristics of the substance with a correspondingly high rate of response and low side effects.

Adult↗

Improving the sensitivity of the time trade-off method: results of an experiment using chained TTO questions.

We test a chained time trade-off (TTO) approach to estimating health gains from interventions by asking respondents to directly compare the "before" and "after" intervention health states in the TTO framework. Respondents with experience of both health states were used, thus minimising biases stemming from confusion surrounding health descriptions. We found that responses to these direct comparisons were much more likely to capture a perceived change in health status than the conventional approach to TTO estimation. This is an important finding because the TTO method is preferred by practitioners to many other direct generic methods of health status valuation both on empirical grounds and because it is based on the notion of opportunity cost, which is central to consumer theory, requiring respondents to express their preferences in terms of foregoing some of one good in exchange for more of another (unlike a rating scale).

Health Services Research↗