Establishment of tyrosinase sequence database in normally pigmented Indians and Japanese for rapid determination of novel mutations

BACKGROUND: Many mutations of the tyrosinase gene have been reported in oculocutaneous albinism type I (OCA1) patient. In the future, a greater number of novel mutations will be found as the search for pathological mutations in the tyrosinase genes of OCA patients from various ethnic origins. For rapid determination in future whether an observed mutation is a polymorphism or a novel pathological one, sequence databases of the gene of various ethnic people are needed. OBJECTIVE: We established a sequence database of the tyrosinase gene of Japanese as well as Indian people. METHOD: We collected DNA from 109 Japanese and 103 Indians with normal pigmentation and analyzed their tyrosinase gene using a direct sequencing method. RESULT: The database shows an apparent difference between the two ethnic groups in polymorphisms of the tyrosinase gene namely, Q402 allele, Y192 allele and IV2+24 insT were found in the Indian population, but not in the Japanese. On the other hand, some Japanese had IV2-21 insT but none of the Indians did. The database supports the notion that the tyrosinase gene evolved and extended separately in the two ethnic groups. And the developing database confirmed that the reported mutations causing Indian and Japanese OCA were not among the polymorphisms in the database, which conversely gives genetical proof of the "genuine" pathological mutations. CONCLUSION: Eventually, the sequence database we established will contribute to demonstrating novel mutations of albinism in Indians and Japanese.     

Tuberculosis verrucosa cutis of the scrotum

A 13-year-old boy had asymptomatic slowly progressive warty growth on the scrotum for 4 years. Examination revealed a 4 cm x 2 cm keratotic, nontender, indurated plaque on the right side of the scrotum. Histopathological examination of the lesion showed epithelioid cell granuloma with giant cells and lymphocytes in the dermis. Mantoux test was 15 mm x 20 mm. A diagnosis of tuberculosis verrucosa cutis of the scrotum was made. Six months of therapy with INH 150 mg and rifampicin 300 mg daily resulted in complete clearance of the lesion.     

Efficacy of H, antihistamine, corticosteroids and cyclophosphamide in the treatment of chronic dermographic urticaria

H, antihistamines relieve urticaria by blocking the action of histamine on the target tissue, while demonstration of autoantibodies in the sera of a proportion of the patients having chronic idiopathic urticaria, use of immunosuppressive drugs for the treatment of these patients has acquired the greater rationality. We evaluated the role of corticosteroids and cyclophosphamide in the treatment of chronic dermographic urticaria. Twenty-five patients, 13 males and 12 females, between 18-53 years in age, having chronic dermographic urticaria were taken up for this study. The patients were divided into three groups. Group I patients (n=9) were treated with cetirizine hydrochloride 10 mg per day orally, group II patients (n=7) were treated with betamethasone 2 mg along with cyclophosphamide 50 mg along with cetirizine 10 mg per day for a total period of 4 weeks. The patients were evaluated every week to record the therapeutic response and side effects, and then followed up without treatment for a period of 6 months to look for recurrence of the urticaria, if any. Six patients in group I and all the patients in group II and group III had complete remission while the remaining patients in group I had partial relief. The side effects included drowsiness in 4 patients. All the patients in group II had weight gain, 4 patients had acne and 2 patients developed cushingoid features. Majority of the patients relapsed within 3 days after stopping the treatment. Supplementation of the treatment with oral corticosteroids or cyclophosphamide was more effective in controlling the symptoms as compared to cetirizine alone. But a four weeks supplementation was not adequate for preventing the relapses when the drugs were withdrawn.     

Chronic pain. Sources of late-life pain and risk factors for disability

The prevalence of pain peaks in middle age and decreases thereafter, according to most epidemiologic studies of complaints of pain. However, this apparent decrease in pain in older adults may be a statistical artifact. Eighty to 85% of persons experience a significant health problem that predisposes them to pain at some time after age 65. With aging, patients experience less frequent head, abdominal, and chest pain and more frequent joint pain. Women are more likely to report musculoskeletal pain and multiple pain sites than men, but there are no gender differences for reports of chest and abdominal pain. Many patients with chronic pain have clinically significant depressive symptoms and low self-reported quality-of-life scores.     

Is 30-Day Mortality after Admission for Heart Failure an Appropriate Metric for Quality?

Background

The Centers for Medicare and Medicaid Services (CMS) model for publicly reporting national 30-day-risk-adjusted mortality rates for patients admitted with heart failure fails to include clinical variables known to impact total mortality or take into consideration the culture of end-of-life care. We sought to determine if those variables were related to the 30-day mortality of heart failure patients at Geisinger Medical Center.

Development of OMP based indirect ELISA to gauge the antibody titers in bovines against Pasteurella multocida

Pasteurella multocida (P. multocida) is an important pathogen of various domestic animals. The outer membrane proteins (OMPs) play a major role in pathogenesis and immunogenicity of P. multocida. The aim of the study was to develop indirect enzyme linked immuno sorbant assay (ELISA) based on OMPs to ascertain the antibody titers in animals post-infection or to gauge the potency of vaccine. The OMPs were extracted and purified from P. multocida P:52 (vaccine strain) and P. multocida B:2 isolated from natural outbreak of Haemorrhagic septicaemia (HS) and analyzed on SDS PAGE and through western blot. The OMPs profile of the vaccine strain and the isolate from the natural outbreak of HS were found to be similar. Optimization of various components viz. coating antigens, anti-species conjugate, etc. were carried out against both anti-P. multocida hyper immune and pre immune serum. Validation of OMP based indirect ELISA assay to measure immune response against P. multocida in bovine revealed 91% diagnostic sensitivity (DSN) and about 100% diagnostic specificity (DSP) at 25% cut off. OMP based indirect ELISA was found to be more specific, but less sensitive as compared to WCL based assay.Key Words: Diagnostic sensitivity, Diagnostic specificity, Indirect ELISA, Outer membrane proteins, Pasteurella multocida     

Cells with Fc gamma receptors from normal donors suppress granulocytic macrophage colony formation

We investigated the role of normal human marrow cells with Fc receptors for IgG (Fc gamma+) on autologous granulocyte-macrophage colony (GM- CFC) formation. It was found that Fc gamma+ normal human marrow cells, both with (E+) or without receptors for sheep erythrocytes suppressed GM-CFC at as low a concentration as 0.25 X 10(5) cells/ml of culture. A similar effect was observed with E- Fc gamma+ but not E+ Fc gamma+ peripheral blood cells. Suppression by Fc gamma+ cells did not require mitogen activation and was not inactivated by irradiation (2000 R). This report presents a new in vitro regulatory mechanism for GM-CFC growth in normal donors.