Five genetic markers in the interleukin 1 family in relation to inflammatory bowel disease

Background—An imbalance between theproinflammatory cytokine interleukin 1β (IL-1β) and theanti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) has beenpostulated as a pathogenic factor in inflammatory bowel disease (IBD).
Aims—To study allelic frequenciesof novel polymorphisms in the genes for IL-1β and IL-1ra in patientswith IBD and to assess the relation between ex vivo cytokine productionand allelic variants of the IL-1β and IL-1ra genes.
Subjects—Two hundred and seventyhealthy controls, 74 patients with ulcerative colitis (UC), 72 withCrohn's disease (CD), 40 with primary sclerosing cholangitis for theallelic frequencies, and 60 healthy individuals for the ex vivostimulation test.
Methods—Genotyping was performed bypolymerase chain reaction and subsequent cleavage with specificendonucleases (Mwo1, MspAI1, Alu1, Taq1, BsoF1) for five novelrestriction fragment length polymorphisms (RFLPs) in the genes forIL-1ra and IL-1β.
Results—No significant differences were found inthe allelic frequencies or allele carriage rates of the markers in theIL-1β and IL-1ra genes between CD, UC, and healthy controls. Noassociation between the genetic markers and cytokine production levelswas observed. Patients with UC carried the combination of both the infrequent allele of the Taq1 RFLP and the Mwo1 RFLP significantly morefrequently (35.2% in UC versus 71.1% in controls).
Conclusions—UC is associatedwith carriage of both infrequent alleles of the Taq1 and Mwo1 RFLPs.However, it could not be confirmed whether the association reflects apathogenic mechanism underlying UC.

     

Imported rickettsioses: think of murine typhus

van der Kleij FGH, Gansevoort RT, Kreeftenberg HG, Reitsma WD (University Hospital Groningen, the Netherlands). Imported Rickettsioses: think of murine typhus (case report). J Intern Med 1998; 243 :177–79. Murine typhus is a disease still prevalent in many parts of the world. Because the incidence in the US and Europe has declined rapidly, physicians in these continents have become unfamiliar with the clinical picture. Murine typhus is associated with significant morbidity and fatalities do occur, especially in the elderly and when late recognized. We present a patient with murine typhus that illustrates the wide variety of symptoms in this disease, which makes diagnosis difficult. However, if one keeps the possibility of murine typhus in mind, it is easily diagnosed and treated.     

The role of torovirus in nosocomial viral gastroenteritis at a large tertiary pediatric centre

OBJECTIVE:

To describe the viral etiology and epidemiology of nosocomial viral gastroenteritis (NVG) at a tertiary care pediatric hospital and identify any changes over the past two decades.

METHODS:

Retrospective review of all patients with laboratory-confirmed NVG at The Hospital for Sick Children (Toronto, Ontario), from January 1, 2004, to December 31, 2005.

RESULTS:

One hundred forty-two episodes of NVG were found among 133 patients, occurring in 0.48 of 100 admissions. The median age was two years; 42% were <1 year of age and 41% were immunocompromised. The most commonly detected pathogen was torovirus (67% of episodes), followed by rotavirus (19%) and adenovirus (9%). Seventy-five cases (53%) were epidemiologically linked in 32 separate clusters (median cluster size two, range two to four). The NVG rate fell from 0.63 of 100 to 0.22 of 100 admissions after March 2005 (P<0.001) when enhanced infection control precautions were instituted in response to an outbreak of vancomycin-resistant Enterococcus.

CONCLUSIONS:

Torovirus remains the most commonly identified cause of NVG at The Hospital for Sick Children. Most NVG cases were epidemiologically linked, and a significant reduction in cases occurred after the institution of enhanced infection control practices following an outbreak of vancomycin-resistant Enterococcus. Improved education and surveillance for NVG should lead to further reduction in this problem.     

Alternatively spliced tissue factor promotes breast cancer growth in a β1 integrin-dependent manner

Full-length tissue factor (flTF), the coagulation initiator, is overexpressed in breast cancer (BrCa), but associations between flTF expression and clinical outcome remain controversial. It is currently not known whether the soluble alternatively spliced TF form (asTF) is expressed in BrCa or impacts BrCa progression. We are unique in reporting that asTF, but not flTF, strongly associates with both tumor size and grade, and induces BrCa cell proliferation by binding to β1 integrins. asTF promotes oncogenic gene expression, anchorage-independent growth, and strongly up-regulates tumor expansion in a luminal BrCa model. In basal BrCa cells that constitutively express both TF isoforms, asTF blockade reduces tumor growth and proliferation in vivo. We propose that asTF plays a major role in BrCa progression acting as an autocrine factor that promotes tumor progression. Targeting asTF may comprise a previously unexplored therapeutic strategy in BrCa that stems tumor growth, yet does not impair normal hemostasis.     

HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis.

BACKGROUND: Susceptibility to inflammatory bowel disease (IBD) is partially genetically determined and the HLA class II genes are candidates for a role in genetic susceptibility to IBD, because their products play a central role in the immune response. Multiple studies have reported associations between HLA-DR or -DQ phenotypes and either ulcerative colitis or Crohn's disease, but much of the data are still controversial. AIMS: To estimate overall associations between HLA class II phenotypes and IBD, and to establish the relative risk conferred by HLA-DR and -DQ phenotypes by meta-analysis. METHODS: Medline was searched for publications reporting on the relation between IBD and HLA class II phenotypes. Raw data were extracted by recalculating the number of phenotypes or the number of alleles of the main antigens. Odds ratios and confidence intervals were calculated according to the Mantel-Haenszel method. RESULTS: DR2, DR9, and DRB1*0103 were positively associated with ulcerative colitis, and a negative association was found for DR4 and ulcerative colitis. For Crohn's disease a positive association was found with DR7, DRB3*0301, and DQ4 and a negative association with DR2 and DR3. CONCLUSIONS: Both ulcerative colitis and Crohn's disease are associated with specific HLA class II phenotypes. Further analysis of these phenotypes and subgroup analysis may elucidate how these alleles contribute to susceptibility to IBD.     

Cardiovascular disease in the Netherlands, 1975 to 1995: decline in mortality, but increasing numbers of patients with chronic conditions

OBJECTIVE: To examine the relation between trends over time in mortality and hospital morbidity caused by various cardiovascular diseases in the Netherlands. DESIGN: Trend analysis by Poisson regression of national data on mortality and hospital admissions from 1975 to 1995. SUBJECTS: The Dutch population. RESULTS: All cardiovascular diseases combined were responsible for 39% of all deaths and 16% of all hospital admissions in 1995. From 1975 to 1995, age adjusted cardiovascular mortality declined by an annual change of -2.0% (95% confidence intervals (CI) -2.1% to -1.9%), while in the same period age adjusted discharge rates increased annually by 1. 3% (95% CI 1.1% to 1.5%). Around 60% of the gain in life expectancy in this period was related to lower cardiovascular mortality. For mortality, major reductions were seen in coronary heart disease (annual change -2.9%) and in stroke (-2.1%), whereas the increase in hospital admissions was mainly caused by chronic manifestations of coronary heart disease (5.1%), heart failure (2.1%), and diseases of the arteries (1.8%). In recent years, the gap between men and women at risk of dying from coronary heart disease became smaller for those aged 相似文献   

Partial plasma exchange using albumin replacement: removal and recovery of normal plasma constituents

Using albumin and crystalloid as the only replacement fluids, the effect of partial plasma exchange on the removal and recovery of normal plasma constituents was studied. The results of 30 procedures on 10 individuals were evaluated. Four patterns of removal are described: reduction in the concentration of fibrinogen and C3 were greater than would be expected based upon the extent of the exchange, while IgG, IgM, cholesterol, alkaline phosphatase and SGPT were removed as expected. Reduction of serum glutamicoxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), amylase, and creatine phosphokinase (CPK) averaged 17% less, and uric acid, calcium and K+ averaged 53% less than expected. Concentrations of HCO-3 and glucose did not change. The mean recovery for all constituents except fibrinogen, C3, cholesterol. IgG and IgM was near 100% at 48-72 hr postpheresis. The 72-hr recovery of fibrinogen and complement was 66% and 60%, respectively. Cholesterol recovery was also slow, requiring a minimum of 1 wk to reach prepheresis levels. Measured at a time when quantitative IgM levels were still reduced, alloantibody agglutinating activity (anti-A and anti-B) in a postpheresis sample exceeded prepheresis agglutinating activity. These data demonstrated that, depending upon quantity and frequency of pheresis, partial plasma exchange using albumin replacement may cause progressive marked reduction in concentrations of immunoglobulin, complement, fibrinogen, and cholesterol. Furthermore, newly synthesized antibody may have increased biologic activity.     

Priming of human neutrophils with N-formyl-methionyl-leucyl- phenylalanine by a calcium-independent, pertussis toxin-insensitive pathway

Resting neutrophils may be "primed" to augmented effector function, eg, superoxide (O2-) production in the respiratory burst, upon a second stimulation with a variety of soluble agonists including formylated methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA). At priming concentrations of FMLP (5 x 10(-9) mol/L) that did not initiate O2- generation, two metabolic activities were noted: (1) approximately a threefold increase in the baseline intracellular calcium (Ca++i) level, that was not dependent on extracellular Ca++, and (2) a rapid rise in intracellular pH that was blocked by 5-(N,N- dimethyl) amiloride (DA), that had no effect on the Ca++i response to priming. Furthermore, there were no significant increases in inositol metabolites in cells primed and stimulated with FMLP compared with cells receiving the stimulating dose of FMLP alone and pretreatment with pertussis toxin (PT) (before the addition of the priming -5 x 10(- 9) mol/L dose of FMLP), whereas abolishing the response to FMLP during the second stage of stimulation, had (1) no effect on FMLP-primed cells subsequently stimulated with PMA, and (2) only partially ablated the rise in Ca++i initiated with FMLP. That FMLP priming involved distinctive processes to those of the well characterized FMLP-coupled Ca++-dependent activation cascade was shown by the full priming effect attained in a Ca++-free buffer, which did not sustain an O2- response to a second-stage FMLP stimulation, but sustained a primed response to PMA. These data demonstrate that FMLP primes human neutrophils by a Ca++-independent and PT-insensitive pathway, offering a functional model for studying heterogeneous FMLP receptor-coupled reactions.     

Epidemiology of reflex syncope

Clinical Autonomic Research - Cost-effective diagnostic approaches to reflex syncope require knowledge of its frequency and causes in different age groups. For this purpose we reviewed the...