Association of HLA-DQA1*03011-DQB1*0301 haplotype with the development of respiratory scleroma.

OBJECTIVE: Respiratory scleroma (RS) is a progressive, chronic, granulomatous disease caused by Klebsiella rhinoscleromatis. There is only one report of RS association with HLA-DQ3. In this study, molecular association of HLA class II and RS was determined. STUDY DESIGN AND SETTING: Nine RS patients and 163 healthy controls were compared. DQA1, DQB1, and DRB1 loci were typed. RESULTS: Statistical analysis demonstrated association between DQB1*0301 and susceptibility to RS (P(c) = 0.004). Haplotype analysis showed an association of DQA1*03011-DQB1*0301 (P = 1.21E-19) and DRB1*0407-DQA1*03011-DQB1*0301 (P = 0.0002). CONCLUSIONS: Results established that DQA1*03011-DQB1*0301 haplotype is a strong risk factor for development of RS.     

No more Hiroshimas

Dyer reports on the ninth World Congress of International Physicians for the Prevention of Nuclear War (IPPNW), held in Hiroshima, Japan, in October 1989. Taking as their theme "No more Hiroshimas," IPPNW participants visited the sites of the only acts of nuclear war -- the 1945 U.S. bombings of Hiroshima and Nagasaki that ended World War II. Scientific sessions updated information on the health effects of radiation. The congress issued an appeal for "a new agenda of moral priorities" that urges the implementation of five measures: the immediate cessation of all nuclear testing; a halt to the production of bomb-grade fissile material; conversion of secret weapons laboratories to open scientific institutes addressing environmental issues; reallocation of 50% of military spending to health and environmental projects; and the establishment of a U.N. Peace Research Centre at Hiroshima and a scholarship program to educate future world leaders about nuclear war.     

Hyperthermic modulation of macrophage-tumor cell interactions

Hyperthermia in the febrile (41° C) or tumor therapeutic (42° C) ranges is known to alter tumor-host interactions: there are reports of either inhibitory or enhancing effects on tumor metastasis and various host defense mechanisms. Historically, this has been an area of conflicting and often anecdotal reports, and there are still significant gaps in our knowledge of the effects of temperature on tumor-host interactions. However, we believe that the tools are now available to further our understanding of the complex relationships between febrile episodes or therapeutically applied heat and various tumor-host cytotoxic mechanisms, and that potentially important and exploitable relationships can be defined. In this review we give an overview of the current status of this field and the factors that have shaped it. We also describe our recent experimental work with macrophages and their monokines, primarily tumor necrosis factor (TNF), which we feel offers new scientific and clinical opportunities for future studies.     

Tuberculous vertebral osteomyelitis in the new millennium: still a diagnostic and therapeutic challenge

In order to determine the clinical features and current prognosis of tuberculous vertebral osteomyelitis, the charts of all patients diagnosed with definite or probable tuberculous vertebral osteomyelitis from January 1983 to June 2002 (n=78) were reviewed. The mean delay to diagnosis was 6.1 months. Sixty-five (83.3%) patients had inflammatory spinal pain, 35 (44.9%) had some neurological deficit, and only 27 (34.6%) had fever. Paravertebral, epidural, and psoas abscesses were detected in 73.1, 65.4, and 24.4% of the cases, respectively. Culture was positive in 48% of the percutaneous biospies and in 61.7% of the open biopsies. After histological findings were included, the diagnostic yield of percutaneous biopsies was 68%. Fifty-five (70.5%) patients required surgical treatment at some stage of the disease. Although no deaths were directly attributable to tuberculous vertebral osteomyelitis and only 5.1% of patients relapsed, the mean overall hospital stay was 69.1±36.9 days, and 30 (38.5%) patients had severe functional sequelae. In conclusion, diagnosis of tuberculous vertebral osteomyelitis requires a high degree of suspicion. Percutaneous biopsy should be undertaken as soon as possible in any patient with compatible symptoms or radiological images in order to initiate suitable therapy.     

Soluble class I histocompatibility antigens (s-HLA) and beta 2-microglobulin at delivery

In this work we have quantified soluble class I histocompatibility antigens (s-HLA) and beta 2-microglobulin (beta 2 m) in sera of HIV+ or HIV- mothers at delivery and in cord blood sera of their newborn children. The results obtained for beta 2 m show that cord blood sera of newborn children have higher concentrations than their mothers, implying that most of the beta 2 m in the newborn is self-produced as described previously. s-HLA serum concentrations in the newborn children are significantly lower than in their mothers or in age-matched controls. Moreover, HIV+ mothers have significantly higher serum concentrations than HIV- mothers or an age-matched control group. These results suggest that s-HLA does not cross the placental barrier.     

Multiple dimensions of familial psychopathology affect risk of mood disorder in children of bipolar parents.

The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participated in the study. Lifetime DSM-IV diagnoses of the bipolar offspring were assessed with the Schedule for Affective Disorders and Schizophrenia for School Age Children Kiddie-SADS-Present and Lifetime Version (SADS-PL). Parents were interviewed using the Family History Research Diagnostic Criteria (FH-RDC) which were used to calculate a continuous familial loading score (FL) for unipolar disorder, bipolar disorder, and for substance use disorder in first- and second-degree relatives of the adolescents. FL for unipolar disorder and substance use disorder were strong and independent predictors for lifetime mood disorders in the adolescents. The gender adjusted hazard ratios for mood disorders in the children were 1.5 (95% confidence interval (CI) = 1.2-2.0) for FL of unipolar disorder and 1.8 (95% CI = 1.3-2.4) for FL of substance use disorder. Expression of mood disorders in children of bipolar parents varies with the degree of additional FL of unipolar disorder and substance use disorder in the extended family.     

A genomic analysis of chicken cytokines and chemokines.

As most mechanisms of adaptive immunity evolved during the divergence of vertebrates, the immune systems of extant vertebrates represent different successful variations on the themes initiated in their earliest common ancestors. The genes involved in elaborating these mechanisms have been subject to exceptional selective pressures in an arms race with highly adaptable pathogens, resulting in highly divergent sequences of orthologous genes and the gain and loss of members of gene families as different species find different solutions to the challenge of infection. Consequently, it has been difficult to transfer to the chicken detailed knowledge of the molecular mechanisms of the mammalian immune system and, thus, to enhance the already significant contribution of chickens toward understanding the evolution of immunity. The availability of the chicken genome sequence provides the opportunity to resolve outstanding questions concerning which molecular components of the immune system are shared between mammals and birds and which represent their unique evolutionary solutions. We have integrated genome data with existing knowledge to make a new comparative census of members of cytokine and chemokine gene families, distinguishing the core set of molecules likely to be common to all higher vertebrates from those particular to these 300 million-year-old lineages. Some differences can be explained by the different architectures of the mammalian and avian immune systems. Chickens lack lymph nodes and also the genes for the lymphotoxins and lymphotoxin receptors. The lack of functional eosinophils correlates with the absence of the eotaxin genes and our previously reported observation that interleukin- 5 (IL-5) is a pseudogene. To summarize, in the chicken genome, we can identify the genes for 23 ILs, 8 type I interferons (IFNs), IFN-gamma, 1 colony-stimulating factor (GM-CSF), 2 of the 3 known transforming growth factors (TGFs), 24 chemokines (1 XCL, 14 CCL, 8 CXCL, and 1 CX3CL), and 10 tumor necrosis factor superfamily (TNFSF) members. Receptor genes present in the genome suggest the likely presence of 2 other ILs, 1 other CSF, and 2 other TNFSF members.     

Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men

Differences in the presence of nine urovirulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men have been studied. Hemolysin and necrotizing factor type 1 occur significantly more frequently among isolates causing prostatitis than among those causing cystitis (P < 0.0001) or pyelonephritis (P < 0.005). Moreover, the papGIII gene occurred more frequently in E. coli isolates associated with prostatitis (27%) than in those associated with pyelonephritis (9%) (P < 0.05). Genes encoding aerobactin and PapC occurred significantly less frequently in isolates causing cystitis than in those causing prostatitis (P < 0.01 and P < 0.0001, respectively) and pyelonephritis (P < 0.01 and P < 0.0001, respectively). No differences in the presence of Sat or type 1 fimbriae were found. Finally, AAFII and Bfp fimbriae are no longer considered uropathogenic virulence factors since they were not found in any of the strains analyzed. Overall, the results showed that clinical isolates producing prostatitis need greater virulence than isolates producing pyelonephritis in women or, in particular, cystitis in women (P < 0.05). Overall, the results suggest that clinical isolates producing prostatitis are more virulent that those producing pyelonephritis or cystitis in women.