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Biomedical subjects

R Shahin

Publications and source records attributed to R Shahin.

At least 19 recordsLinked to original sources
PubMed1999

Comparison of the effects of dopaminergic and serotonergic activity in the CNS on the activity of the immune system.

This work demonstrates that the natural killing function of the innate immune system is affected in psychiatric disorders related primarily to serotonergic pathways in the CNS rather than to psychiatric disorders which involve mainly dopaminergic pathways. Only depressive patients demonstrated low natural killer (NK) cell activity, which is inversely correlated to the intensity of depression and could be reversed by serotonin selective re-uptake inhibitors concomitant with clinical improvement. This phenomenon is absent in Parkinson's and schizophrenic patients, in whom no reduction in NK activity was observed. Also, no effect on NK activity could be demonstrated following the specific respective treatments by dopamine (D2) blockers or agonists.

Adolescent↗
PubMed1999

Methicillin-resistant Staphylococcus aureus carriage in a child care center following a case of disease. Toronto Child Care Center Study Group.

OBJECTIVES: To study the prevalence of methicillin sodium-resistant and methicillin-sensitive Staphylococcus aureus colonization in a child care center following the diagnosis of community-acquired methicillin-resistant S. aureus (MRSA) disease in a previously well 2 1/2-year-old attendee and to determine the optimal site of detection of S. aureus. DESIGN: Point prevalence survey and questionnaire administration. SETTING: A Toronto, Ontario, child care center. INTERVENTIONS: Parents were provided with general information. Consenting parents completed a questionnaire and permitted screening of their child at 1 or more of throat, nose, and perianal sites. Families of children who were culture positive for MRSA were offered screening and suppressive therapy. Nasal and perianal swabs were obtained from child care center staff and screened. RESULTS: Of 201 children, 164 (81.6%) had completed questionnaires and had undergone screening at 1 or more sites; 38 staff members (100%) completed questionnaires and were screened. A 26-month-old classroom contact with chronic dermatitis had MRSA detected only on perianal swab. Of 3 adult household contacts of the index case and 2 adult and 1 child contacts of the classroom contact, only the 7-year-old sibling of the classroom contact was positive for MRSA. By pulse-field gel electrophoresis, these isolates were identical and not related to any of the common strains circulating in regional health care institutions. Of 40 children with S. aureus (24.4%), 33 had cultures at 3 sites, of which the throat was more sensitive (22 [67%]) than the nostrils (15 [46%]) or perianal sites (8 [24%]). There was a tendency for higher carriage of S. aureus in children with certain risk factors, including personal hospitalization (prevalence ratio, 2.9; 95% confidence interval, 0.6-12.1), family member hospitalization (prevalence ratio, 2.0; 95% confidence interval, 0.6-6.6), and visiting the hospital emergency department (prevalence ratio, 3.2; 95% confidence interval, 0.7-14.5), all in the previous 6 months. CONCLUSIONS: To our knowledge, this is one of the first recognized cases of MRSA disease and apparent transmission in a child care center. Throat and perianal site screenings have a higher sensitivity in identifying children colonized with S. aureus than nasal culturing. Infection with MRSA should be suspected in disease unresponsive to standard antibiotic therapy.

Adolescent↗
PubMed1998

Contribution of regulation by the bvg locus to respiratory infection of mice by Bordetella pertussis.

Whooping cough is an acute respiratory disease caused by the small, gram-negative bacterium Bordetella pertussis. B. pertussis expresses several factors that contribute to its ability to cause disease. These factors include surface-associated molecules, which are involved in the adherence of the organism to respiratory epithelial cells, as well as several extracellular toxins that inhibit host defenses and induce damage to host tissues. The expression of virulence factors in B. pertussis is dependent upon the bvg locus, which consists of three genes: bvgA, bvgS, and bvgR. The bvgAS genes encode a two-component regulatory system consisting of a sensor protein, BvgS, and a transcriptional activator, BvgA. Upon modification by BvgS, BvgA binds to the promoter regions of the bvg-activated genes and activates transcription. One of the bvg-activated genes, bvgR, is responsible for the regulation of the bvg-repressed genes, the functions of which are unknown. The fact that these genes are regulated by the bvg locus suggests that they play a role in the pathogenesis of the bacterium. In order to evaluate the contribution of bvg-mediated regulation to the virulence of B. pertussis and determine if expression of the bvg-repressed genes is required for the virulence of B. pertussis, we examined the ability of B. pertussis mutants, defective in their ability to regulate the expression of the bvg-activated and/or the bvg-repressed genes, to cause disease in the mouse aerosol challenge model. Our results indicate that the bvgR-mediated regulation of gene expression contributes to respiratory infection of mice.

Adhesins, Bacterial↗
PubMed1997

Bilateral brachial plexopathy after E. coli sepsis.

A 67-year old patient, operated for closure of ileostomy 3 days before, developed E. coli sepsis with suspected peritonitis. Two days later, pain and weakness in the shoulder girdle, scapula and proximal upper limb muscle appeared simultaneously, followed by marked atrophy. Electromyography (EMG) examination manifested bilateral active denervation of upper brachial plexus. Any trial to isolate a pathogenic factor other than the E. coli failed. Due to the bilateral proximal upper limb's paralysis, grooming and upper-body dressing obliged the patient to ask for complete assistance. In other daily living activities he was partially independent.

Activities of Daily Living↗
PubMed1997

[Suprascapular nerve entrapment in a basketball player].

A basketball player was shown to have a suprascapular nerve lesion without any history of shoulder girdle trauma. This acute neuropathy, never previously described in basketball players, is a result of repeated micro-trauma, due to nerve traction over the coracoid notch during violent movement ("dunking" most probably). Clinically, he was unable to abduct his arm and had some difficulty in external rotation. He developed atrophy in both the supra- and the infraspinatus muscles. Nerve conduction latency to the supraspinatus muscle was 8.0 ms, and to the infraspinatus, 8.5 ms. The compound muscle action potential registered in the supraspinatus was 1.224 mV, and in the infraspinatus, 1.237 mV. After 3 weeks of inactivity, recovery was spontaneous and practically complete.

Adult↗
PubMed1995

Adjuvanticity and protective immunity elicited by Bordetella pertussis antigens encapsulated in poly(DL-lactide-co-glycolide) microspheres.

Purified Bordetella pertussis antigens, encapsulated in biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) microspheres, were evaluated for their immunogenicity and ability to elicit a protective immune response against B. pertussis respiratory infection. Microencapsulated pertussis toxoid, filamentous hemagglutinin, and pertactin all retained their immunogenicity when administered parenterally. Intranasal immunization with a low dose (1 micrograms) of encapsulated filamentous hemagglutinin, pertussis toxoid, or pertactin elicited strong specific immunoglobulin G and immunoglobulin A antibody responses in respiratory secretions that were greater in magnitude than the responses elicited by the same doses of unencapsulated antigen. Intranasal immunization with as little as 1 micrograms of encapsulated pertussis antigen prior to infection reduced the bacterial recovery by 3 log10 CFU. However, intranasal immunization with the same low doses of unencapsulated antigens did not reduce infection. Intranasal administration of a combination of 1 micrograms of each of the microencapsulated pertussis antigens was more effective in reducing bacterial infection than administration of any single microencapsulated antigen. Intranasal administration of microencapsulated B. pertussis antigens elicits high levels of specific antibody coinciding with protection against infection when these microspheres are administered to the respiratory tract. These data provide evidence of the respiratory adjuvanticity of three different DL-PLC microsphere preparations, each of which contains a unique B. pertussis antigen.

Adjuvants, Immunologic↗
PubMed1992

A vir-repressed gene of Bordetella pertussis is required for virulence.

Coordinate regulation of gene expression in Bordetella pertussis is controlled by the products of the vir locus, BvgA and BvgS. In the presence of modulating signals such as MgSO4 and nicotinic acid, expression of vir-activated genes (vag) is reduced, while expression of vir-repressed genes (vrg) is maximal. We have cloned one of these vir-repressed genes, vrg-6, in Escherichia coli. DNA sequencing has shown that vrg-6 is contained on a single EcoRI restriction endonuclease fragment and is predicted to code for a protein of 105 amino acids with a molecular weight of 11,441. The predicted protein product appears to have two domains, one consisting of seven hydrophobic proline-rich pentameric repeats and the other consisting of five alkaline trimeric repeats. Southern blot analysis has revealed vrg-6-homologous sequences in the chromosomes of Bordetella bronchiseptica and Bordetella parapertussis, but, unlike Bordetella pertussis, these species do not express vrg-6-homologous RNA when grown under modulating conditions. In order to assess the role of vrg gene products in B. pertussis pathogenesis, two 18323 derivatives which harbor TnphoA insertions in vrg genes were analyzed in a mouse model of respiratory infection. Strain SK6, which carries a vrg-6::TnphoA mutation, failed to induce lymphocytosis and was significantly less able to colonize lungs and trachea than its parent strain 18323 or than SK18, which harbors a TnphoA fusion in the vrg-18 locus. This is the first evidence that a vir-repressed gene may play an important role in the virulence of B. pertussis and the pathogenesis of whooping cough.

Amino Acid Sequence↗
PubMed1991

Characterization of vir-activated TnphoA gene fusions in Bordetella pertussis.

The expression of many of the known virulence determinants of Bordetella pertussis is coordinately regulated by the vir regulatory locus and reduced in response to environmental signals called modulators. We have previously identified eight TnphoA gene fusions in B. pertussis in which the expression of alkaline phosphatase was maximal in the absence of the modulators nicotinic acid and MgSO4. We have termed the genes identified by these fusions vir-activated genes. Here we report the characterization of these TnphoA mutant strains. Four fusion strains were defective in known virulence determinants. For one of these, fusion strain SK39, Southern blot hybridization demonstrated that TnphoA was inserted in the S1 subunit gene of pertussis toxin. Hemagglutination assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblots identified three fusions strains, SK16, SK75, and SK91, that were defective in filamentous hemagglutinin. Whereas all three filamentous hemagglutinin-defective mutants showed either normal or enhanced colonization, the pertussis toxin-defective mutant showed a marked defect in pulmonary persistence. Of the four other fusion strains, two were deficient in outer membrane proteins. One of these, strain SK8, was defective in a major outer membrane protein of 95 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This strain colonized mouse lungs less well and did not induce lymphocytosis after aerosol challenge. The other strain, SK34, was defective in four outer membrane proteins, three of which were detectable only on a Western blot with polyclonal sera against B. pertussis. Two of our gene fusion strains did not show any defect in identifiable vir-regulated proteins.

Animals↗
PubMed1991

Acute inflammatory demyelinating polyneuropathy following bone marrow transplantation.

Acute inflammatory demyelinating polyneuropathy (AIDP) appeared in two patients following allogeneic bone marrow transplantation (BMT). In one transplanted patient (but not in the donor) T cells were sensitized against peripheral nervous system myelin. This could reflect a change in the T cell repertoire in a different milieu. In this context, AIDP might be part of graft-versus-host disease or another associated autoimmune disorder following BMT.

Adolescent↗
PubMed1988

Host resistance to mucosal gram-negative infection. Susceptibility of lipopolysaccharide nonresponder mice.

The effect of Lps on the resistance of mice to gram-negative infection was compared in two genetically different backgrounds; C3H and C57BL. To mimic the natural sequence of pathogenetic events, infection was induced via a mucosal surface (intravesically), with Escherichia coli which remained at the mucosal site and Salmonella typhimurium which invaded to e.g., livers and spleens. Susceptibility was assessed as the bacterial persistence in kidneys, bladders, livers, and spleens at various times after infection. The initial clearance of both bacterial species from the mucosal site was significantly impaired in Lpsd mice both in the C3H and C57BL backgrounds. In the C57BL mice, additional unknown determinants conferred increased resistance to mucosal infection compared to the C3H mouse. For S. typhimurium, these resistance factors and alleles at the Lps locus dominated over Ity as determinants of resistance to mucosal infection. The Itys genotype conferred a significant increase in the susceptibility only to systemic infection, especially in the Lpsd, Itys mice. These results demonstrate an important difference between the genetic determinants of host resistance at mucosal and systemic sites, and emphasize the role of LPS induced host defense mechanisms for bacterial clearance from mucosal surfaces.

Animals↗
PubMed1985

Interferon modulates the leukotriene C4-induced non-adherence properties of leukocytes: acquisition of an asthmatic phenotype.

We have previously shown that peripheral blood leukocytes (PBL) of asthmatic patients acquire non-adherence properties after challenge with leukotriene C4 (LTC4), whereas PBL of normal individuals do not. Hence the use of the LTC4-induced leukocyte-adherence-inhibition (LAI) assay enables one to recognise an asthmatic phenotype on the basis of the ability of PBL to respond in vitro to LTC4. To examine the possibility that alpha interferon (IFN alpha) may have relevance to the pathogenesis of bronchial asthma, various concentrations of IFN were incubated with normal PBL and the acquisition of non-adhering properties was measured. We found that following 24 h incubation with 500 U/ml IFN, normal PBL were induced to respond to a standard dose of LTC4, and this reaction was abrogated by FPL 55712 and cyclohexamide.

Adult↗
PubMedDate not supplied

The first reported cluster of food-borne cyclosporiasis in Canada.

INTRODUCTION: Prior to 1996, sporadic cases of cyclosporiasis in Canada were most often associated with foreign travel and outbreaks throughout the world were associated with contaminated drinking water. In May 1996, the North York Public Health Department was notified of three laboratory-confirmed cases of cyclosporiasis among persons who attended a luncheon at a religious institution. A ceremonial bath (mikvah) was initially identified as a possible source of exposure to contaminated water. METHODS: Guests of a luncheon were interviewed regarding food, beverage and water exposure. The institution kitchen and water sources were inspected and environmental testing was performed. RESULTS: Eating strawberry flan, decorated with rasberries and blueberries, was associated with developing illness (relative risk = 2.13, p = 0.02). There was no evidence that water exposure was associated with illness. DISCUSSION: This event was the index Canadian cluster of a widespread North American outbreak associated with imported Guatemalan raspberries. The local investigation highlights the role of public health departments in multijurisdictional food-borne outbreaks of emerging pathogens.

Adolescent↗