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     

Effect of caffeic acid phenethyl ester on cartilage in experimental osteoarthritis

Systemic lupus erythematosus (SLE) is characterized by the presence of various autoantibodies and the deposition of immune complex, which is cleared by Fcgamma receptors. Genotype analysis was done to investigate whether the FcgammaRIIIA-176F/V polymorphism is a risk factor for SLE in Koreans. We genotyped 145 Korean SLE patients and 75 control subjects for FcgammaRIIIA-176F/ V. After amplifying a 1.7-kb fragment containing the Fcgamma/RIIIA-176F/V polymorphic site using two FcgammaRIIIA gene-specific primers, we performed a nested polymerase chain reaction (PCR) for allele-specific genotyping at position 559 in FcgammaRIIIA. FcgammaRIIIA genotype or allele distribution was not significantly different between lupus patients and controls, and also between lupus nephritis patients and healthy controls. Neither creatinine clearance, 24 h urine proteinuria, number of American College of Rheumatology (ACR) criteria, nor the Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index was different according to the genotype. In conclusion, FcgammaRIIIA-176F/V polymorphism is not associated with SLE in Koreans.     

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.     

Deaf child--a general practitioner's responsibility

The power of a child's speaking language never develops if he is deaf. Deafness persists if it is not detected early. Childhood deafness is either congenital or acquired. At birth, doctors or attendants can detect deafness by arousing the baby with sudden loud noise. At 4 months onwards mothers and doctors can detect deafness. The baby at this age can turn its head or eyes towards the source of the sound. By 12 months to 2 years of age it is very difficult to detect deafness. By the age of 3 years children again become co-operative and it becomes easier to detect deafness. Children should always be screened for deafness while being admitted to nursery classes. In school going age ie, 5 years onwards loss of tests can be employed to detect deafness. If a child is suspected be deaf, a general practitioner's responsibility is to refer him to an ENT specialist earlier. Any child whose mother believes her child is deaf should be given due attention. Otitis media with effusion, enlarged adenoid, chronic suppurative otitis media, recurrent otitis media are some diseases to be carefully looked into by the general practitioners. Now-a-days cochlear implantation surgery is gaining popularity to give hearing to deaf child. Moreover regular screening for deafness should be included school heath programme.     

Laryngeal reconstruction by platysma myofascial flap after vertical partial laryngectomy

BACKGROUND: Many methods of glottic reconstruction have been described for patients undergoing vertical partial laryngectomy to reestablish the glottic integrity. METHODS: Fifteen patients with T2 squamous cell carcinoma of the glottis were included in this prospective clinical trial. All patients were treated by vertical partial laryngectomy with laryngeal reconstruction by platysma myofascial flap. The surgical procedure and flap design were described. Vocal function was assessed by videolaryngostroboscopy and subjective and objective voice analysis before and after surgery. RESULTS: Complete neoglottic closure and acceptable voice quality were obtained by platysma myofascial flap in all cases. No statistically significant difference was found between the preoperative and postoperative acoustic parameters. CONCLUSIONS: Platysma myofascial flap provides the basic requirements for laryngeal reconstruction with its own favorable characteristics and also allows complete glottic closure without interfering with respiration and deglutition. This technique may be an effective alternative achieving an acceptable quality of voice.