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Biomedical subjects

M Hussain

Publications and source records attributed to M Hussain.

At least 19 recordsLinked to original sources

Enterococcus faecalis GP1764 induces an early differential gene expression in the intestine on key pathways related to cellular immune response and gut barrier function in chickens.

The aim of the present study was to elucidate the mode of action of Enterococcus faecalis GP1764 in improving performance traits during the starter phase by analyzing genome-wide gene expression and its interaction with microbial populations in the intestine of chickens challenged with an NSP-rich diet. At day 7, microbiota populations from ileal and cecal contents and transcriptomics from jejunal and cecal mucosa were analyzed between Control (Ctrl) and Enterococcus faecalis GP1764 (EntF) groups. Results from microbiota analysis demonstrated that EntF shifted β-diversity indices in ileum (neutral (p= 0.006) and phylogenetic (p= 0.006)) and caecum (phylogenetic (p= 0.017)). Transcriptomics revealed 43 differentially expressed genes for EntF vs. Ctrl in the jejunal mucosa. Of these, MHCY-36 (MHC-I-Related), RAG2 and MUC19-like genes were upregulated in EntF vs. Ctrl, protein-coding genes with immunomodulatory capacities as supported by GSEA and Cytoscape-ClueGo pathway analyses. Results suggest an intestinal immunomodulation induced through presentation of B vitamins metabolites, synthetized by EntF, to an undescribed subset of innate-like unconventional T lymphocytes in chickens, similar to MAIT cells in mammals. These cells could contribute to antibacterial responses and repair of damaged barrier tissue after inflammatory processes. The upregulation of the MUC19-like gene expression observed in the jejunal mucosa can protect gut integrity via the promotion of mucus production by goblet cells. Finally, RAG2, involved in V(D)J coding segments recombination in B- and T-cells may provide a greater recognition of foreign invaders, allowing the animals to efficiently fight against pathogenic infections. Collectively, these results suggest an important role of EntF in promoting the capacity of animals to rapidly act against pathogenic challenges, herein, inducing resilience towards dietary ingredients with anti-nutritional activity that impart moderate inflammation in chickens.

Enterococcus faecalis↗

Greater antiarrhythmic activity of acute 17beta-estradiol in female than male anaesthetized rats: correlation with Ca2+ channel blockade.

BACKGROUND AND PURPOSE: Female sex hormones may protect pre-menopausal women from sudden cardiac death. We therefore investigated the effects of the main female sex hormone, 17beta-estradiol, on ischaemia-induced cardiac arrhythmias and on the L-type Ca2+ current (ICaL). EXPERIMENTAL APPROACH: In vivo experiments were performed in pentobarbital-anaesthetized rats subjected to acute coronary artery occlusion. ICaL was measured by the whole-cell patch-clamp technique, in rat isolated ventricular myocytes. KEY RESULTS: Acute intravenous administration of 17beta-estradiol as a bolus dose followed by a continuous infusion, commencing 10 min before coronary artery occlusion, had dose-dependent antiarrhythmic activity. In female rats 300 ng kg(-1) + 30 ng kg(-1) min(-1) 17beta-estradiol significantly reduced the number of ventricular premature beats (VPBs) and the incidence of ventricular fibrillation (VF). A ten fold higher dose of 17beta-estradiol was required to cause similar effects in male rats. In vitro 17beta-estradiol reduced peak ICaL in a concentration-dependent manner. The EC50 was ten-fold higher in male myocytes (0.66 microM) than in females (0.06 microM). CONCLUSIONS AND IMPLICATIONS: These results indicate that 17beta-estradiol has marked dose-dependent antiarrhythmic activity that is greater in female rats than in males. A similar differential potency in blocking ICaL in myocytes from female and male rats can account for this effect. This provides an explanation for the antiarrhythmic activity of 17beta-estradiol and gender-selective protection against sudden cardiac death.

Anesthesia↗

Mobilisation into cotton and spread of a recombinant cotton leaf curl disease satellite.

Analysis of a DNA beta satellite associated with a recently identified cotton leaf curl disease (CLCuD) strain indicated it to be recombinant, with most of the molecule originating from CLCuD DNA beta but with some sequence from a satellite isolated from tomato. Analysis of both archival (pre 2001) and recent cotton samples, shows the recombinant satellite is confined to a small area but was not present in cotton prior to 2001. This indicates that the recombinant DNA beta was recently mobilized into cotton, likely from tomato, and that recombination plays a role in the evolution of these satellites.

Base Sequence↗

A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting.

A 10-month longitudinal household study of pre-school children and their families was undertaken with monthly visits collecting epidemiological data and nasopharyngeal swabs in Hertfordshire, England from 2001 to 2002. Pneumococcal culture was with standard methods. In total, 121 families (489 individuals) took part. Mean prevalence of carriage ranged from 52% for age groups 0-2 years, 45% for 3-4 years, 21% for 5-17 years and 8% for >or=18 years. Carriage occurred more than once in 86% of children aged 0-2 years compared to 36% of those aged >or=18 years. The most prevalent serotypes in the 0-2 years age group were 6B followed by 19F, 23F, 6A and 14. Young children were responsible for the majority of introductions of new serotypes into a household. Erythromycin resistance (alone or in combination) occurred in 10% of samples and penicillin non-susceptibility in 3.7%. Overall the recently licensed 7-valent conjugate vaccine (PCV) would protect against 64% of serotypes with no intra-serogroup cross protection and 82% with such protection. Nasopharyngeal carriage of S. pneumoniae is common in a UK setting in the pre-conjugate vaccine era. PCV would protect against a large proportion of carriage isolates. However, the impact of vaccination on non-vaccine serotypes will need to be monitored.

Adolescent↗

Squamous cell carcinoma and basal cell carcinoma arising in a naevus sebaceous of Jadassohn: case report and literature review.

The development of a basal cell carcinoma within a naevus sebaceous of Jadassohn (NSJ) has commonly been reported. However, the development of a squamous cell carcinoma (SCC) is rare. There have been several reports of SCC arising within a NSJ but many contain little or ambiguous clinical information. A thorough review of the current English language literature has identified only three other well documented cases of SCC arising in a NSJ. Of these only one was a case of simultaneous occurrence of squamous and basal cell carcinoma. We report the second case of both malignancies arising within the same NSJ.

Adult↗

Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States.

The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection.

Adult↗

Serotonin syndrome:case report and current concepts.

Selective serotonin reuptake inhibitors (SSRI's) are increasingly being used as the first line therapeutic agent for the depression. It is therefore not unusual to see a case of overdose with these agents. More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. The clinical picture of serotonin syndrome (SS) is non-specific and there is no confirmatory test. SS may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.

Adolescent↗

Improving kidney and live donation rates in Asia: living donation.

Organ transplantation started with organs donated by living subjects. Increasing demands brought cadaveric organ donation. The brain-death law, mandatory for this procedure, is prevalent in all countries involved in organ transplantation except Pakistan. Spain is the leading country in cadaveric organ donation (32.5 pmp). Despite the sources of living and cadaveric organs, both heart-beating and non-heart-beating, the gap between the demand and supply has widened. An example is the United States, where the numbers of patients on the waiting list for kidney transplantation have risen from 30,000 in 1988 to more than 116,000 in 2001. This has caused a resurgence in living donors all over the world. These can be related, unrelated, spousal, marginal, or ABO-incompatible donors. Family apprehensions, medical care costs, and nonexistent social security can be barriers to this form of organ donation. Unrelated organ donation can open the doors to commercialism. To make this process more successful, transplantation should be made reachable by all sectors of the population. This is possible when transplantation is taken to the public sector institutions and financed jointly by the government and community. To increase living organ donation especially in Asian countries, which face barriers of low literacy rates, ignorance, and cultural and religious beliefs, more efforts are needed. Public awareness and education play an important role. Appreciation and supporting the donors is necessary and justified. It is a noble act and should be recognized by offering job security, health insurance, and free education for the donor's children.

Cadaver↗

Recent advances in detrusor muscle function.

Contractile activation of detrusor smooth muscle is initiated by the release of transmitters from motor nerves. Acetylcholine is a ubiquitous transmitter, as also is adenosine triphosphate (ATP) in many animal bladders and in people from several patient groups with pathological bladder function. In recent years there has been progress in explaining several cellular mechanisms that link transmitter release to contraction and these will be considered. The lifetime of ATP in the neuromuscular junction is finite and broken down ultimately to adenosine, which can exert modulatory control of contractile activation. Adenosine depresses nerve-mediated contractions and two sites of action have been proposed: an action on the motor nerves via A receptors to depress further transmitter release and a less well-defined depressant effect on the detrusor muscle. The Ca2+ ions that activate the contractile proteins are derived from intracellular stores, which releases their content via IP receptor activation and Ca2+-induced Ca2+ release. Filling of the stores in the rest interval is mediated via transmembrane flux of Ca2+through Ca2+ channels. Activation of the channels is regulated by the level of the intracellular [Ca2+], via activation and inactivation of Ca2+-sensitive K channels. Thus, Ca2+ store filling is regulated by intracellular [Ca2+] via a negative feedback process. The presence and physiological function of spontaneous contractions in detrusor remain contentious and little is known about their origin. One possibility is that they originate from random Ca2+ sparks, i.e. localized transient increases of [Ca2+] that may eventually progress to generate a cellular Ca2+ transient. Observations by confocal microscopy have revealed the presence of such sparks, especially near the cell membrane, and thus provide a cellular basis for spontaneous contractions. Finally, the questions arises as to whether detrusor smooth muscle is a functional syncitium. The demonstration of small gap junctions by electron microscopy and the demonstration of the gap junction protein connexin45 indicate that the muscle mass may indeed be functionally connected. The implications regarding the spread of excitation are discussed.

Animals↗

Estimation of spilled hydrocarbon volume--the state-of-the-art.

With the increase in the environmental awareness and reorganization of the need for its protection, the study of soil and groundwater contamination and its remediation have become the focus of numerous researchers. Intentional and unintentional release of hydrocarbon into soil and subsurface pose a great threat to the biosphere environment. The quantification of spilled volume has primary importance for carrying out the remediation work and is considered a first step in the remediation hierarchy. Different investigators approached the problem from many viewpoints, and the resulting achievements are so extensive and scattered that it seems essential to inventory the completed works. This paper presents a systematic study of the available experimental and theoretical works. A complete picture of the present status of the problem is also provided. Issues that remain unresolved and obscure by the current day investigators are pointed out to facilitate future research directions and more comprehensive analyses of the quantification of spilled hydrocarbon volumes.

Environmental Monitoring↗

Stomal complications of ileal conduits are significantly higher when formed in women with intractable urinary incontinence.

PURPOSE: The ileal conduit is held to be the safest and simplest form of urinary diversion. There are few reports about long-term problems after ileal conduit formation, especially intractable urinary incontinence in females. We reviewed long-term stomal complications in patients with an ileal conduit. MATERIALS AND METHODS: Notes on 93 consecutive patients in whom an ileal conduit was created were reviewed. Information was collected on patient demographics, indications for an ileal conduit and long-term complications, in particular parastomal and incisional hernias, stomal retraction, stenosis or prolapse and the development of a redundant loop. Mean followup available was 63.4 months (range 1 to 434). RESULTS: A total of 33 males with a mean age of 60.1 years (range 2 to 78) and 60 females with a mean age of 48.2 years (range 4 to 79) underwent ileal conduit diversion. The main indications for an ileal conduit were intractable incontinence in 44 patients (47%), cancer in 31 (33%) and interstitial cystitis in 8 (9%). In male, continent female and incontinent female patients A parastomal hernia developed in 3 (9%), 2 (9.5%) and 12 (31%), an incisional hernia developed in 1 (3%), 1 (4.8%) and 2 (5%), stomal retraction developed in 0, 2 (9.5%) and 12 (31%), stomal stenosis developed in 0 (0%), 1 (4.8%) and 6 (15.4%), and a redundant loop developed in 0 (0%), 2 (9.5%) and 5 (12.8%), respectively. A total of 23 patients (24.7%) required further surgery for stomal problems with 13 (57%) requiring more than 1 reoperation, of whom 9 were incontinent females. CONCLUSIONS: An ileal conduit is associated with a stomal complication rate of 34.4% (61% in incontinent females and 18% in other patients) and a 4.3% incisional hernia rate. Reoperation is required for stomal complications in 24.7% of cases. Stomal complication rates and reoperation rates vary by sex and the indication for ileal conduit, and they are significantly higher for those performed for intractable urinary incontinence in females.

Adolescent↗

Sustained response after a 2-year course of lamivudine treatment of hepatitis B e antigen-negative chronic hepatitis B.

Lamivudine has demonstrated efficacy for the treatment of hepatitis B e antigen-negative chronic hepatitis B (e-CHB). However, treatment withdrawal after 1 year has been associated with a high rate of relapse while long-term treatment is associated with increasing risks of drug resistance. We report our treatment experience of 50 Chinese-Canadian patients with e-CHB. All patients received lamivudine for 2 years. Treatment was withdrawn at month 24 in patients who had undetectable hepatitis B virus (HBV) DNA by PCR and normal aminotransferases during the second year of therapy. All patients had HBV genotype B or C. Biochemical response at months 6, 12 and 24 was 74%, 71% and 66%, respectively. HBV DNA was undetectable at months 6, 12 and 24 by hybrid capture and PCR assays in 100%, 92% and 86%; and 94%, 88% and 74% patients, respectively. The cumulative rates of genotypic resistance (GR) after 1 and 2 years were 15% and 25%, respectively. Four (44%) patients with GR experienced a hepatitis flare. The probability of clinical and virological relapse 6, 12, and 18 months after treatment withdrawal were 12% and 30%, 18% and 50%, and 30% and 50%, respectively. Reinstitution of lamivudine resulted in prompt virological and biochemical responses. Our study demonstrates that a sustained response can be achieved after a 2-year course of lamivudine in a subset of patients with e-CHB.

Adult↗

Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family.

The improved understanding of the molecular biology of urothelial malignancies is helping to define the role of new targets and prognostic indices that can direct the most appropriate choice of treatment for advanced disease. Many human tumors express high levels of growth factors and their receptors that can be used as potential therapeutical targets. Tyrosine-kinase receptors, including many growth factor receptors such the receptors for epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and Her2/neu, have been found overexpressed in urothelial tumors. For many of these growth factor receptors, the degree of expression has been associated with the progression of cancer and a poor prognosis. Among the best studied growth factor receptors are the two members of EGF receptor familiy EGFr (ErbB-1), and Her2/neu (ErbB-2). Several preclinical studies in bladder cancer models, have confirmed that systemic administration of growth factor inhibitors inhibits the growth and metastasis of human transitional cell carcinoma established in the bladder wall of athymic nude mice. Additional studies indicate that therapy with EGFR inhibitors enhances the activity of conventional cytoreductive chemotherapeutic agents, in part by inhibiting tumor cell proliferation, angiogenesis, and inducing apoptosis. Novel targeted therapy hold promise to improve the current results of bladder cancer treatment. Based on the success seen with anti-HER2 monoclonal antibodies (Herceptin) and the promising results with EGFR targeted agents (IMC-C225 Cetuximab, ZD1389 Iressa, OSI-774 Tarceva, GW 57016) in other tumor types, and based on the results obtained in preclinical models, there is a great interest in assessing these agents in patients with bladder cancer. Several trials are now ongoing testing these new agents alone or in combination with chemotherapy in bladder cancer patients. The integration of these newer biologic agents, probably to supplement rather than to supplant chemotherapeutic drugs, should be a primary direction of research with the objective to interfere with multiple aspects of bladder cancer progression. However, the value of integration of biologically targeted agents into combined modality treatment for patients with bladder cancer has still to be proven.

Animals↗