Vitamin D-dependent rickets (VDDR) type 1: case series of two siblings with a CYP27B1 mutation and review of the literature / Raquitismo dependente de vitamina D: tipo 1: série de casos de dois irmãos com mutação CYP27B1 e revisão da literatura

Abstract Two siblings presented with clinical and biochemical features of rickets, initially suspected as hypophosphatemic rickets. There was no improvement initially, hence the siblings were reinvestigated and later diagnosed as having vitamin D-dependent rickets (VDDR) type 1 due to a rare mutation in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. Both siblings improved with calcitriol supplementation. The initial presentation of VDDR is often confusing and algorithmic evaluation helps in diagnosis. We also present a brief review of the literature, including genetics.

Resumo Dois irmãos apresentaram características clínicas e bioquímicas do raquitismo, com suspeita clínica inicial de raquitismo hipofosfatêmico. Não houve melhora no início, portanto os irmãos foram reavaliados e, posteriormente, diagnosticados com raquitismo dependente de vitamina D (VDDR) tipo 1 devido a uma rara mutação no gene CYP27B1, que codifica a enzima 1a-hidroxilase. Ambos os irmãos melhoraram com a suplementação de calcitriol. A apresentação inicial do VDDR geralmente é confusa e a avaliação algorítmica ajuda no diagnóstico. Também apresentamos uma breve revisão da literatura, incluindo genética.

Prostate specific antigen ratio: for diagnosis and assessment of aggressiveness of malignancy of prostate.

The search for a perfect tumour marker, which would be able to distinguish benign from malignant enlargement of prostate accurately, is still not complete. Total Prostate Specific Antigen (TPSA), a good test, has it's own inadequacies but Free Prostate Specific Antigen (FPSA) to TPSA ratio is emerging as a better adjuvant to it. This prospective study was done to verify the utility of FPSA to TPSA ratio in diagnosis of malignancy of prostate and its relationship to Gleason grading (indicating the aggressiveness) of adenocarcinoma of prostate. 100 patients with urinary symptoms, who were above fifty years of age and had prostatic enlargement, formed the study group. TPSA and FPSA were assayed by ELISA method and FPSA to TPSA ratio was calculated. Prostatic biopsy of all the cases was obtained and diagnostic histopathology and Gleason grading (in cases where adenocarcinoma was diagnosed) was done. Sensitivity, specificity, predictive value of positive test and predictive value of negative test for TPSA and FPSA to TPSA ratio were calculated. They were found to be 100%, 76.7%, 74.1% and 100% for TPSA and 82%, 100%, 100%, 89% for FPSA/TPSA ratio. Thus making it very obvious that FPSA to TPSA ratio is an excellent adjuvant to TPSA for diagnosis of malignancy of prostate increasing the specificity and predictive value for positive test. An inverse correlation (correlation coefficient = -0.95) was also found between PSA ratio and aggressiveness of prostate cancer, pointing towards its capability to predict the histological (Gleason) grade of the tumour.

Characterization and utilization of monoclonal antibodies reactive to Yersinia pseudotuberculosis.

The 3 murine monoclonal antibodies, Yps1, Yps2 and Yps3 reactive to Y. pseudotuberculosis can be stabilized and all were found to be of IgG type. Monoclonal antibody, Yps1, recognized a glycoprotein antigen of the organism with reactivity at the 55-75 kDa region, while Yps2 and Yps3 recognized protein antigens of Y. pseudotuberculosis 65 kDa and 26-28 kDa molecular weight regions, respectively. The specificity of monoclonal antibodies was tested using dot ELISA and Western blotting with whole cell organisms or whole cell sonicated soluble antigens of different Yersinia species, Salmonella typhi, Klebsiella pnemoniae, Streptococcus abortus-equi and Escherichia coli. Monoclonal antibody, Yps1 exhibited cross-reactivity with soluble antigens and whole cell preparations of Y. pestis. Yps2 cross-reacted to soluble antigens of all the tested bacteria. Reactivity of monoclonal antibody, Yps3 was restricted to Y. pseudotuberculosis and Y. pestis with soluble antigen preparations. No reaction was observed with Yps2 and Yps3 to whole cell organism preparations from tested bacteria including Y. pseudotuberculosis. The co-agglutination reagent prepared by sensitizing staphylococcal cells with Yps1 monoclonal antibody produced a positive agglutination with all the 4 Y. pseudotuberculosis isolates and the 3 Y. pestis strains tested. Sandwich dot ELISA using monospecific antisera as a capture antibody and a monoclonal antibody, and Yps3 as a revealing antibody had a high level of specificity in detecting Y. pseudotuberculosis antigens.