Malakoplakia of urinary bladder.
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Biomedical subjects
Publications and source records attributed to P Seth.
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Daily urinary creatinine excretion and creatinine coefficient of eighty-four healthy medical students have been studied for three consecutive days. Daily creatinine excretion has been observed to be higher in the male subjects compared to the female counterparts. Creatinine excretion has been observed to be dependent on body weight of the subjects. The variability from subject to subject was higher than observed by most other workers. Day to day consistency within the same subject was rather low. Creatinine coefficient was computed per kg of body weight as well as per kg of lean body weight. In both the cases, it has been found to be higher in the males than in the females. Though an important factor, yet body weight of a subject alone could not explain satisfactorily wide variability of creatinine excretion in the present study. The possible influencing factors have been discussed along with clinical implications.
Deep inspiration shifted the mean frontal plane axis of P, QRS and T waves to the right in all the cases. Greater degree of shift in AP and AQRS was observed in cases where the resting axis had been 0 degrees to +30 degrees and minimum shift was observed where the resting axis was between +61 degrees to +90 degrees. Axis of the T wave though shifted to the right with deep inspiration in all the cases but there had been no statistically significant difference in the degree of shift in the three groups. In none of the case, axis changed from normal to abnormal degree.
In this work we have explored the use of adenoviral vectors for the purging of cancer cells from hematopoietic stem cell (HSC) autografts. We showed that a recombinant adenovirus expressing the herpes simplex-1 thymidine kinase gene (AD-tk) plus ganciclovir (GCV) killed HELA cells more effectively than did GCV alone. HELA cells were then mixed with human HSCs and exposed to AD-tk/GCV. AD-tk/GCV reduced the number of HELA colonies to 4% of control values, with no detectable reduction in the hematopoietic progenitor, colony forming unit-granulocyte/monocyte (CFU-GM). Similar studies of the JB6 non-Hodgkins lymphoma cell line showed a reduction to 5% of controls; studies of MCF-7, a breast carcinoma cell line, showed a reduction to 30% of controls, with no CFU-GM toxicity. Thus, AD-tk mediated selective killing of contaminating tumor cells. We also evaluated a recombinant adenovirus encoding the tumor suppressor gene p53 (AD-p53). AD-p53 was able to selectively kill all three cell lines (reducing tumor colonies approximately 100-fold) without any toxicity to CFU-GM. Although both AD-tk/GCV and AD-p53 were effective in these experiments, AD-p53 seemed to be more potent. Adenoviral vectors show promise for selectively targeting cancer cells that contaminate HSC autografts.
A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 cells infected with AdCD were 1000-fold more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus. Cell mixing experiments indicated that only 10% of AdCD-infected cells in a population were needed to induce complete cytotoxicity of noninfectious cells exposed to 5-FC. This suggests that bystander effects play an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into human breast MDA-MB-231-derived tumors grown as xenografts in nude mice, followed by daily intraperitoneal injection 5-FC was sufficient to inhibit tumor growth. These results suggest that in vivo gene therapy for breast cancer using AdCD is feasible.
The cytotoxicity of a recombinant adenovirus expressing the wild type tumor suppressor gene p53 (AdWTp53) was studied in two human breast cancer MCF-7 sublines selected for resistance to adriamycin (MCF-Adr) and mitoxantrone (MCF-Mito). Although the levels of wild type p53 protein following infection with AdWTp53 are comparable in all cell lines, the two drug-resistant MCF-7 sublines were 300- and 18-fold more sensitive to killing by AdWTp53 compared with the drug-sensitive parental MCF-7 cell lines. In each cell line, AdWTp53 infection led to cell cycle arrest, and reduction of Cdk2 and cyclin B1-Cdc2 activity. Nucleosomal DNA fragmentation analysis (as a function of apoptosis) following AdWTp53 infection revealed that, while the parental MCF-7 cells failed to undergo apoptosis, both drug-resistant cell lines showed distinct DNA laddering. In MCF-Adr cells, a combination treatment of AdWTp53 and adriamycin was much more toxic than either of the reagents used individually. Finally, exposure of a mixed population of MCF-Adr and CD34+ cells to AdWTp53 selectively prevented MCF-Adr cell colony formation, while there was no inhibition of CFU-GM colony formation from CD34+ cells. These findings suggest that some drug-resistant human breast cancers may be effectively treated with adenovirus expressing wild type p53.
The role of wild-type human p53 protein in enhancing camptothecin cytotoxicity was examined by infecting human prostate PC3 cells with adenovirus expressing human wild-type p53 gene (Adwtp53). The prostate PC3 cells are null for p53 gene. Infection induced the synthesis of both wtp53, and WAF1 (p21) proteins, resulting in growth arrest of PC3 cells. In the presence of camptothecin, an inhibitor of topoisomerase 1, significant increases in both p53 and p21 proteins were detected in Adwtp53-infected PC3 cells. While Adwtp53 and camptothecin, as single agents, caused apoptosis and cell death, combinations of camptothecin and Adwtp53 were better in inducing apoptosis and cell death in PC3 cells. In contrast, cisplatin neither stabilized p53 and p21 proteins nor enhanced DNA fragmentation when combined with Adwtp53 in PC3 cells, indicating specificity for camptothecin. These observations suggest that introduction of wild-type p53 gene with topoisomerase I inhibitors may offer a clinical advantage for the treatment of prostate tumors containing mut53 or null for p53 gene.
Polymerase chain reaction (PCR) has been found to be a sensitive and rapid method to confirm a clinical diagnosis of tuberculosis. We evaluated PCR for M. tuberculosis complex specific MPB64 gene for the diagnosis of pulmonary tuberculosis, in a double blind study. One hundred and eighty-two clinical samples (sputum, bronchioalveolar lavage and pleural fluid) from patients with a clinical diagnosis of pulmonary tuberculosis and 72 samples from patients with non-tubercular pulmonary lesions and normal healthy individuals were included. The samples were coded and clinical details were concealed from the laboratory, where conventional diagnostic methods and PCR were carried out independent of each other. On decoding and analysing the data, PCR was positive in 59% of single sputum samples from clinically diagnosed pulmonary tuberculosis, while M. tuberculosis could be grown in 18% of the samples. PCR could identify M. tuberculosis in 81.8% of the culture positive sputum samples. PCR was also positive in 71.4% of bronchioalveolar lavage (BAL) fluid and 60.7% pleural fluid samples from clinically suspected cases, which were mostly culture negative. On comparison with response to treatment, PCR was positive in 79.5% of patients who improved on anti-tuberculosis treatment, with a positive predictive value of 92%. PCR for MPB64 gene provides a useful alternative for the diagnosis of pulmonary tuberculosis from sputum and paucibacillary samples like BAL and pleural fluid in which conventional methods show low sensitivity, especially in areas from which strains show a low copy number of other PCR targets like the IS 6110 insertion sequence.
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