Expression of B7 molecules in the eye during experimental autoimmune anterior uveitis (EAAU)

PURPOSE: We have reported that CTLA4-Fc, a fusion protein that binds B7, prevents the induction of EAAU and reduces the severity of disease in Lewis rats. Since B7.1 and B7.2 have distinctive roles in other autoimmune diseases, we investigated their roles in the development of EAAU. METHODS: Lewis rats were immunized with melanin associated antigen (MAA). Eyes were collected at different stages of EAAU and the expression of B7 on iris and ciliary body (ICB) cell suspensions determined by flow cytometry analysis. The incidence of EAAU after treatment with anti B7, and the requirement of B7.1 and B7.2 for proliferation and cytokine production of lymphoid cells to MAA were also studied. RESULTS: B7.2 is up-regulated in resident ICB cells or bone-marrow derived cells which have infiltrated the ICB by day 10 and remains elevated during the acute phase of disease. B7.1 is expressed later during the acute phase. Both B7.1 and B7.2 are down-regulated during remission, with low levels of B7.2 and no detectable B7.1. The incidence of EAAU was reduced by anti-B7.2 treatment and completely inhibited by a combination of both B7.1 and B7.2 antibodies. Neither anti-B7.1 nor anti-B7.2 alone affected proliferation or cytokine production. However, administration of both anti-B7.1 and B7.2 completely inhibited proliferation as well as IL-2 and TNF-alpha production. CONCLUSIONS: B7.1 and B7.2 are expressed in the eye at different times during EAAU. Both B7 molecules are required for the induction of EAAU, although they probably have different roles.     

A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family

Bipolar affective disorder (BPAD) is a complex neuropsychiatric disease characterized by extreme mood swings. Genetic influences affect the disease susceptibility substantially, yet the underlying mechanisms are unknown. We previously described a pedigree in which all five individuals with BPAD and one individual with recurrent major depression were carriers of a reciprocal chromosomal translocation t(9;11)(p24;q23). Gene content analyses of the breakpoint junctions revealed disruption of a gene (DIBD1) at 11q23, a genomic region that has also been implicated in schizophrenia and Tourette syndrome. DIBD1 is predicted to encode a mannosyltransferase similar to Saccaromyces cerevisiae Alg9p of the protein N-glycosylation pathway. The inborn errors of protein N-glycosylation cause congenital disorders of glycosylation in humans. DIBD1 shows uniform expression in the tested subregions of the brain by Northern analysis. Sequence analysis revealed four intra-genic single nucleotide polymorphisms. The valine residue at V289I was conserved in other eukaryotic species, whereas its frequency was approximately 65% in humans. We performed linkage and linkage disequilibrium analyses in two NIMH bipolar pedigree series using four tightly linked simple tandem repeat polymorphisms (STRPs) and the V289I. These analyses overall failed to support a role for DIBD1 in disease susceptibility. The most-significant finding was a lod score of 1.18 (P=0.0098), obtained by an intronic STRP D11S5025, in the subset of 22 multiplex pedigrees. In conclusion, we found that a mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint co-segregating with BPAD in a family. However, its role in the disease susceptibility remains unconfirmed. Electronic Publication     

A survey on community perceptions of jaundice in east Delhi: implications for the prevention and control of viral hepatitis

Using senior health professionals as interviewers, a 30-cluster sampling survey was carried out to investigate community perceptions of pilia (the local word for jaundice) in east Delhi (India). Of 416 persons (mostly mothers of children aged < 2 years) interviewed, 339 (81%) were aware of pilia as an illness. Only 322 (77%), 164 (39%), 73 (18%) and 71 (17%) people knew about correct symptoms, dangers, causes and prevention of pilia. Most of the correct responses were related to the faeco-orally transmitted viral hepatitis. Literate respondents were significantly more aware of pilia (chi 2 52.81, P < 0.0001), its symptoms (chi 2 48.88, P < 0.0001), causes (chi 2 39.34, P < 0.0001), dangers (chi 2 19.3, P = 0.0007), and prevention (chi 2 60.8, P < 0.0001). However, age of the respondents had no significant bearing (P > or = 0.05) on the correctness of responses. About 293 (70%) subjects considered pilia as a treatable illness; of them, 193 (66%) and 77 (26%) respectively expressed their preference for the 'modern' and indigenous systems of medicine for its treatment. In contrast, 110 (38%) respondents said that they would prefer faith healers for the treatment of pilia. Although only 31 (7%) persons were aware of a vaccine against pilia (hepatitis B vaccine), virtually all agreed to have their children immunized if such a vaccine were made available. The study underscores the usefulness of pilia in lay-reporting of viral hepatitis and epidemiological studies on jaundice-associated illnesses and the need for educating the community about its causes and prevention to increase people's participation in controlling viral hepatitis and other diseases that mainly manifest as jaundice.     

Predictive value of the international prostate symptom score for positive prostate needle biopsy in the low-intermediate prostate-specific antigen range

PURPOSE: Serum prostate-specific antigen (PSA) has a restricted predictive value for prostate cancer in the low-intermediate PSA range (2.5-10 ng/ml). Our aim was to determine the predictive value of the International Prostate Symptom Score (IPSS) for positive prostate needle biopsy (PNB) in patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy with a low-intermediate PSA level. PATIENTS AND METHODS: Between 2001 and 2004, the data of 389 consecutive patients applying for any urologic complaint to our department and who underwent TRUS-guided prostate biopsy due to an elevated serum PSA and/or abnormal digital rectal examination (DRE) were retrospectively analyzed. A total of 158 eligible patients with a low-intermediate PSA level were included in the study. The patient's age, PSA, free PSA, free/total PSA, prostate volume, PSA density (PSAD), pre-biopsy IPSS were compared in the positive and negative biopsy groups. RESULTS: Fifty-eight of 158 patients (37%) who underwent TRUS-guided prostate biopsy had positive PNBs. Forty-eight patients (30%) had abnormal DREs. In the positive PNB group, the mean age was older and PSAD was higher, but the means of the prostate volumes and total IPSS were lower (p<0.05). Multivariate analysis demonstrated that age and IPSS were independent predictors of a positive PNB (p<0.05). The odds ratio of mild IPSS for positive PNB controlled for age was 3.0 (95% CI 1.5-6.7). Receiver-operating characteristics analysis revealed a mild IPSS (AUC=0.640) and was a considerable predictor for positive PNB as well as PSAD (AUC=0.648). The sensitivity and specificity of IPSS with a cutoff value of 7.5 points were 31 and 87% for prediction of prostate cancer detection. CONCLUSION: In the low-intermediate PSA range, mild IPSS may be a predictive factor for positive PNB with a similar specificity of PSAD.     

An unusual case of monosomy 18p: minor malformations with speech delay

An unusual case of monosomy 18p with molecular cytogenetic characterization of 18;21 whole arm translocation who had mild speech delay and normal motor development is presented. A 3.5-year-old boy with complaints of speech delay, open mouth and drooling saliva was the child of a 33-year-old healthy mother and 35-year-old nonconsangineous father with unremarkable prenatal history. Beside delayed speech, hyperactive movements, flat nasal bridge, prominent ears, micrognathia, hypotonia, and overriding of left 3rd the on 2nd toe were present. Cytogenetic studies revealed de novo 45,XY del (18) t(18;21)-21 karyotype, which was confirmed by fluorescence in situ hybridization (FISH).     

Deletion analysis and clinical correlations in patients with Xp21 linked muscular dystrophy

We carried out molecular deletion analysis on 142 patients with Duchenne/Becker muscular dystrophy which covered 25 exons of the dystrophin gene. We also evaluated the results by comparing with the clinical findings and examples in the literature. A deletion ratio of 63.7% was achieved. Exon 46 was the most frequently affected region. Interestingly we also observed four cases with muscle promoter (Mp) region deletions which have been rarely reported in the literature.     

Resistive index in febrile urinary tract infections: predictive value of renal outcome

In the absence of specific symptomatology in children, the early diagnosis of acute pyelonephritis is a challenge, particularly during infancy. In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured intrarenal resistive index (RI). We evaluated its ability to predict renal involvement as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. In total 157 patients admitted to the pediatric department of the ili Etfal Hospital with clinical signs of febrile UTI were included in the study. The children were divided into groups according to their age at the time of ultrasonography (US). RI was measured from the renal arteries with Doppler US in the first 72 h in all 157 children. Renal involvement was assessed by ^99mTc-DMSA scintigraphy in the first 7 days after admission. The examination was repeated at least 6 months later if the first result was abnormal. All available patients with an abnormal scintigraphy underwent voiding cystourethrography 4–6 weeks after the acute infection. All patients with vesicoureteral reflux and scarred kidneys were excluded from the study. DMSA scintigraphy demonstrated abnormal changes in 114 of 157 children and was normal in the remaining 43 children. Of these 114 children, 104 underwent repeat scintigraphy, of whom 77 showed partially or totally reversible lesion(s). Of these 77 children, 17 children (22%) with vesicoureteral reflux were excluded. Thus, we compared the 43 children with lower UTI with the 60 children with definite acute pyelonephritis at admission. Kidneys with changes of acute pyelonephritis had a mean RI of 0.744±0.06 in infants, 0.745±0.03 in preschool children, and 0.733±0.09 in patients of school age with upper UTI. However, the mean RI was 0.703±0.06 in infants, 0.696±0.1 in preschool children, and 0.671±0.09 in school-aged patients with lower UTI. The mean RI values were significantly higher in patients with upper UTI (P<0.001). There was a highly significant correlation between RI values and the severity of the renal lesion as ranked by DMSA scintigraphy (P<0.001). When the cut-off RI value was 0.715, there was an 80% sensitivity and a 89% specificity for diagnosing upper UTI. Refluxing kidneys and scarred kidneys also had higher RI values. In conclusion, RI values were increased significantly in children with febrile UTI when renal parenchymal involvement (assessed by DMSA scintigraphy) was present. Our results also support the view that the children with high RI values are at a high risk of reflux, scarring, or both, which was frequently observed in febrile UTI. This might allow identification of patients at risk for severe renal lesions that require more aggressive therapy, investigation, and follow-up than those with lower UTI.An erratum to this article can be found at