Expression of CD133 as a cancer stem cell marker in invasive gastric carcinoma.

INTRODUCTION: Gastric cancer is considered to be the fourth most common malignancy worldwide and the second cause of cancer deaths. Regarding the cancer stem cells (CSCs) theory, they are a small group of tumor cells with unrestricted self-renewal and differentiation abilities that help tumor formation. There is an interest in the utility of CD133 as a promising marker to detect the tumor stem cell population for a variety of solid malignancies including gastric cancer. Tumors that express stem cell markers such as CD133 are found to be more aggressive tumors with poor prognosis and high liability for recurrence. This study aimed to evaluate the immunohistochemical expression of CD133 in invasive gastric carcinoma and study the relation between CD133 immunohistochemical expression and different clinicopathological parameters. MATERIAL AND METHODS: 77 cases of gastric carcinoma were collected from the surgical pathology unit at the Gastroenterology Center, Mansoura University, Egypt. CD133 expression in tumor tissue was evaluated by immunohistochemistry. RESULTS: CD133 expression positively correlated with tumor metastasis and recurrence. Multivariate analysis revealed CD133 positivity to be an independent prognostic factor for tumor recurrence (P = 0.03). CONCLUSION: CD133 is a good marker that can predict tumor recurrence and metastasis in gastric carcinoma. Even though, studies regarding CSCs are still in their initial stages especially those related to CD133 in gastric cancer.

Toll-like receptor 7 gene single nucleotide polymorphisms and the risk for systemic lupus erythematosus: a case-control study.

BACKGROUND: Toll-like receptors (TLRs) are a family of pattern-recognition receptors which play a role in eliciting innate/adaptive immune responses and developing chronic inflammation. So, the aim of this study was to analyze the effect of TLR7 gene single nucleotide polymorphisms (SNPs) rs3853839 and rs179019 on systemic lupus erythematosus (SLE) susceptibility and to assess their relations with various clinical and laboratory data of the patients. METHODS: This is a case-control study including 50 SLE female patients and 50 healthy controls. TLR7 rs3853839 and rs179019 genotyping was performed using real-time polymerase chain reaction (PCR) TaqMan-based allelic discrimination assay. RESULTS: Regarding rs3853839, there was a statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.009). A significant association was detected between TLR7 genotypes (rs385389) and lupus nephritis (p = 0.021). Regarding rs179019, there was no statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.271) CONCLUSION: This study revealed the plausible role of TLR7 rs3853839 SNP in SLE in Egyptian women.

Serum IL-17 in patients with erythema multiforme or Stevens-Johnson syndrome/toxic epidermal necrolysis drug reaction, and correlation with disease severity.

BACKGROUND: There is strong evidence that drug-induced cutaneous eruptions have an immunological component. Interleukin (IL)-17, a proinflammatory cytokine that is predominantly produced by T helper 17 cells, has been linked to various autoimmune and inflammatory diseases. AIM: To measure serum IL-17 levels in patients with cutaneous drug reactions [erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)] in order to study the associations between IL-17 and disease severity. METHODS: In total, 32 patients (13 with EM and 19 with SJS/TEN) and 15 age- and sex-matched healthy controls (HCs) were enrolled. Patients with SJS/TEN were assessed clinically using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Serum IL-17 levels were determined by ELISA. RESULTS: Serum IL-17 levels were significantly higher compared with HCs (16.46 ± 5.21 pg/mL) in the EM (35.1 ± 23.89 pg/mL, P < 0.02) and SJS/TEN (68.19 ± 35.42 pg/mL, P = 0.001) groups. IL-17 levels were also significantly higher in the SJS/TEN group than in the EM group (P = 0.004). Mean affected body surface area percentage was 0.9 ± 0.21 in the EM group and 22.8 ± 10.67 in the SJS/TEN group. The SJS/TEN SCORTEN ranged from 1 to 5, with a mean of 2.5 ± 1. Serum IL-17 level correlated positively with both percentage surface area of detached skin and SCORTEN. CONCLUSIONS: Serum IL-17 levels may have prognostic and diagnostic value in patients with EM or SJS/TEN reactions, and can provide a valuable approach in managment.

Cuticular protein and transcription factor genes expressed during prepupal-pupal transition and by ecdysone pulse treatment in wing discs of Bombyx mori.

We aimed to understand the underlying mechanism that regulates successively expressed cuticular protein (CP) genes around pupation in Bombyx mori. Quantitative PCR was conducted to clarify the expression profile of CP genes and ecdysone-responsive transcription factor (ERTF) genes around pupation. Ecdysone pulse treatment was also conducted to compare the developmental profiles and the ecdysone induction of the CP and ERTF genes. Fifty-two CP genes (RR-1 13, RR-2 18, CPG 8, CPT 3, CPFL 2, CPH 8) in wing discs of B. mori were examined. Different expression profiles were found, which suggests the existence of a mechanism that regulates CP genes. We divided the genes into five groups according to their peak stages of expression. RR-2 genes were expressed until the day of pupation and RR-1 genes were expressed before and after pupation and for longer than RR-2 genes; this suggests different construction of exo- and endocuticular layers. CPG, CPT, CPFL and CPH genes were expressed before and after pupation, which implies their involvement in both cuticular layers. Expression profiles of ERTFs corresponded with previous reports. Ecdysone pulse treatment showed that the induction of CP and ERTF genes in vitro reflected developmental expression, from which we speculated that ERTFs regulate CP gene expression around pupation.

Evaluation of angiotensin converting enzyme gene polymorphism and susceptibility to bronchial asthma among Egyptians.

BACKGROUND: Angiotensin converting enzyme (ACE) is expressed at high levels in the lungs and plays a role in the metabolism of the endogenous peptides involved in asthma pathogenesis. ACE gene polymorphisms have been reported to be linked to asthma. However, the results are conflicting, with no reported studies on Egyptian asthmatics. We aimed to assess ACE gene polymorphism among Egyptian asthmatics, and to determine its possible association with asthma severity. METHODS: This case-control study was conducted on 30 adult asthmatic patients, and 30 healthy controls with no history of asthma or atopy. Atopic status among asthmatics was determined by skin prick test (SPT). Lung functions were assessed by spirometry. Determination of ACE genotypes was performed for all subjects. Total serum IgE levels were measured by ELISA. RESULTS: The frequencies of the DD, ID and II genotypes were 46.7%, 40%, and 13.3%, respectively among the cases, and 33.3%, 40%, and 26.7%, respectively among the controls. No significant differences in ACE genotype distribution were observed between cases and controls (p=0.37). Genotype distribution did not differ according to age of onset or severity of asthma, total serum IgE levels, SPT positivity, or number of positive SPT reactions. Furthermore, ACE polymorphism was not statistically different between asthmatic patients without any associated atopic disease and those with an associated atopic disease. CONCLUSION: The results of our study indicate that ACE gene polymorphism is not significantly associated with bronchial asthma or with its severity among Egyptian adults.

Oxidative stress in lichen planus.

BACKGROUND: Increased reactive oxygen species (ROS) and lipid peroxides have been implicated in the pathogenesis of atopic dermatitis, psoriasis, vitiligo, and lichen planus (LP). We therefore evaluated the status of oxidative stress and the antioxidant defense system in Egyptian patients with LP. METHODS: This study included 45 Egyptian LP patients and 45 healthy volunteers as controls that were age- and sex-matched with the patients. Serum levels of nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), and erythrocyte catalase (CAT) were measured. RESULTS: There was an increase in the serum levels of NO, SOD and the lipid peroxidation product MDA (p = 0, p = 0.009 and p = 0.005, respectively) and a decrease in CAT levels in LP patients compared to controls (p = 0), leading to an imbalance in the antioxidant defense system in our study. Oxidative stress was greater in men than in women because MDA levels were increased (p = 0.045) and erythrocyte CAT levels were decreased (p = 0). In addition, there was also a positive correlation between NO, MDA, and SOD and a negative correlation between erythrocyte CAT and the duration of LP. No relation between the four parameters and the clinical types of LP was noted. CONCLUSION: Our findings point to an increase in oxidative stress and an imbalance in the antioxidant defense mechanisms in LP. This may play a role in the pathogenesis of LP.

Survey of infection control procedures at manicure and pedicure establishments in North York.

OBJECTIVE: To describe infection control practices used by technicians doing manicures and pedicures in an urban setting in Ontario. METHODS: A random sample of 120 establishments was selected from a sampling frame. A survey was designed and administered to technicians through face-to-face interviews. RESULTS: Technicians in 72 establishments were interviewed, representing a 60% response rate. Twenty-nine (40%) of these technicians indicated that they had been immunized against hepatitis B. Technicians re-used almost all instruments even if this was not the intent of the manufacturer. Isopropyl alcohol was the most commonly used disinfectant. Many technicians did not wear gloves while performing procedures. Most did not follow universal precautions when asked how they would react to incidental cuts on either the client or themselves. CONCLUSION: There is a need for the development of infection control protocols for manicure and pedicure establishments since the potential for transmission of infectious diseases does exist.

Protective immunity to Bordetella pertussis requires both B cells and CD4(+) T cells for key functions other than specific antibody production.

To investigate the fundamental nature of protective immunity to Bordetella pertussis, we studied intranasal immunization of adult mice with formalin-fixed B. pertussis (FFBP), followed by aerosol B. pertussis challenge. Mice given two doses of FFBP intranasally completely cleared a subsequent pertussis aerosol challenge from tracheae and lungs (defined as protection), but there was no correlation between levels of specific antibody and clearance of bacteria. Further, transfer of immune serum before aerosol challenge had minimal effects on bacterial burdens. However, pertussis-specific T cells producing interferon gamma but not interleukin 4 or interleukin 10 were detected in draining lymph nodes of FFBP-immunized mice. Significantly, repeated immunization of B cell knockout (BKO) mice resulted in partial protection, and complete protection was reconstituted by transfer of pertussis-immune B cells; reconstituted BKO mice had little if any detectable antipertussis antibodies. Immunization of mice lacking all T cells or lacking CD4(+) T cells did not lead to protection; in contrast, CD8(-) mice were protected. Mice depleted of CD4(+) T cells after immunization but before aerosol challenge, which thus had normal amounts of specific antibodies, were not optimally protected. Taken together, these data indicate that protective immunity to pertussis is dependent on both CD4(+) T cells and B cells, and both cell types provide significant functions other than specific antibody production.

An outbreak of cyclosporiasis in 1996 associated with consumption of fresh berries- Ontario.

BACKGROUND: A large foodborne outbreak of cyclosporiasis occurred in North America in 1996. An index cluster of cases associated with a catered event on May 11, 1996, in Ontario sparked the recognition of this outbreak in Canada. OBJECTIVES: To describe the Ontario experience with the North American outbreak of cyclosporiasis in 1996. PATIENTS AND METHODS: Public health units investigated the index and subsequent event-associated clusters. Investigations included retrospective cohort studies of clusters, traceback of suspect foods and a case-control study of sporadic cases. These activities, coordinated with those in the United States, were part of an international investigation. RESULTS: In Ontario, 232 cases of cyclosporiasis (20 laboratory-confirmed and 72 clinically defined cases associated with seven events plus 140 additional laboratory-confirmed sporadic cases) were identified between May 1 and July 30, 1996. For the index cluster, a strawberry flan with raspberries and blueberries was the only significant exposure (relative risk 2.16, P=0.02). Fresh berries were served at all seven events associated with clusters of cases. Raspberries were definitely served at three events, possibly served at three events, and not served at one event. Only imported berries were available in Ontario in May 1996, when initial clusters and sporadic cases were identified. The raspberries served at the two events with well documented traceback data came from Guatemala. Univariate analyses of the matched case-control study demonstrated that illness was associated with consumption of raspberries (matched odds ratio 21.0, 95% CI 3.48 to 448) and strawberries (matched odds ratio 28.5, 95% CI 4.02 to 478). Further evidence amassed by the international investigation compellingly implicated Guatemalan raspberries as the vehicle of the outbreak. CONCLUSION: Cyclosporiasis may be acquired domestically from the consumption of contaminated produce. The scope and vehicle of this international foodborne outbreak were recognized through a coordinated public health response.

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.

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.

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.

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.

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.

Role of gamma interferon in natural clearance of Bordetella pertussis infection.

Using a mouse model of Bordetella pertussis infection, we have analyzed the role of gamma interferon (IFN-gamma) in bacterial clearance from the respiratory tract. Adult BALB/c mice began to clear a respiratory infection within 3 weeks postinfection, with complete resolution of infection 6 to 8 weeks postinfection. In contrast, neither adult SCID mice (which lack mature B and T lymphocytes) nor adult nude mice (which lack mature T lymphocytes) controlled B. pertussis infection, and both strains died within 3 to 5 weeks postinfection. Short-term T-cell lines generated from the draining lymph nodes of the lungs of infected BALB/c mice were found to be CD4+ and produced IFN-gamma but no detectable interleukin-4. Analyses of IFN-gamma mRNA induction in the lungs of mice following B. pertussis infection showed that in both BALB/c and C57BL/6 mice, IFN-gamma mRNA levels increased sharply by 1 week postinfection and then subsequently declined. Further exploration of a potential role for IFN-gamma demonstrated that infection of adult BALB/c mice depleted of IFN-gamma in vivo with anti-IFN-gamma monoclonal antibodies resulted in greater numbers of bacteria recovered from the lungs than in infected, control BALB/c mice, although IFN-gamma-depleted mice could subsequently clear the infection. Infection of mice which have a disrupted IFN-gamma gene resulted in bacterial clearance with a time course similar to those seen with IFN-gamma-depleted mice. These results indicate that IFN-gamma plays a role in controlling B. pertussis infection.

[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.

Pertussis antigens that abrogate bacterial adherence and elicit immunity.

Infectious disease processes follow the initial steps of adherence of the organism to host tissues and subsequent colonization of the target tissues that can occur through specific adhesion-receptor systems. Bordetella pertussis, the human pathogen that causes whooping cough, has evolved a genetically controlled system whereby adhesins are expressed when they enter the human host. Two adhesins, filamentous hemagglutinin (FHA) and pertactin, mediate the adherence of the bacterium to eukaryotic cells through varied attachment mechanisms, including lectin-like binding sites that interact with sulfated sugars on cell surface glycoconjugates and the ARG-GLY-ASP binding sequence, which recognizes a family of integrins found on the cell surface. The differential expression of relevant receptors by various eukaryotic cells likely plays a role in the pathogenesis and immune response to the bacterium by the host, directing the organism to specific cell types and to specific tissue sites. Substantial evidence exists that the B. pertussis adhesins, FHA and pertactin, elicit immune responses that are protective in animal models for the disease, including serum antibody production and local immune responses in the respiratory tract following nasal administration of encapsulated antigens. Both of these adhesins are components of new acellular pertussis vaccines that have proven safe and highly effective for prevention of serious disease in infants.