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Biomedical subjects

A K Dewan

Publications and source records attributed to A K Dewan.

5 recordsLinked to original sources

Redefinition of dystrophin isoform distribution in mouse tissue by RT-PCR implies role in nonmuscle manifestations of duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is caused by a defect in a 427-kDa membrane-associated protein: dystrophin. The DMD gene also encodes several shorter isoforms which are believed to participate in nonmuscle manifestations of DMD, including abnormal retinal electrophysiology, dilated cardiomyopathy, mental retardation, and hearing defects. The purpose of this work was to determine the normal tissue expression of full-length dystrophin (Dp427) and the dystrophin isoforms Dp260, Dp140, Dp116, and Dp71, to aid in understanding what roles these isoforms might play in DMD nonmuscle manifestations. RT-PCR was performed on mRNA isolated from wild-type C57BL/6J mouse tissues, including brain, cardiac muscle, eye, intestine, kidney, liver, lung, skeletal muscle, spleen, stomach, testis, thymus, and uterus. RT-PCR amplification demonstrated that the isoforms were in a number of tissues which had not been revealed by previous Western and Northern blot analyses. Dp427 was expressed at equal levels in all tissues. Dp260 and Dp140 were present in all tissues tested, but the levels of expression varied. Dp116 was expressed in a subset of tissues and levels of expression varied. Dp71 was constitutively expressed in all tissues, suggesting that this isoform plays a basic role in normal tissue function. The expanded tissue distribution supports the hypothesis that dystrophin isoforms serve essential and unique functions, necessitating further investigation into their potential roles in DMD nonmuscle manifestations.

Actins↗

Role of steroid hormone and growth factor receptors and proto-oncogenes in the behavior of human mammary epithelial cancer cells in vitro.

The cultivation of cells from primary breast cancers is very unpredictable. The majority of breast-cancer-derived cell lines are of metastatic origin. To define the characteristics of tumor cells which govern their ability to grow in vitro as primary cultures as well as continuous or established culture cell lineages, human mammary epithelial cancer (HMEC) cells from 18 cases of unselected primary breast cancer were propagated in culture. Propagation of HMEC cells in vitro as monolayers in primary culture was successful in 10 out of 18 (55.5%) cases, which showed continous proliferation of tumor cells only up to 6-8 passages before they reached senescence. An investigation of the effects of phenotypic expression of estrogen receptors (ER), the progesterone receptors, c-erbB-2 oncoprotein and epidermal growth factor receptors (EGFR) on the capacity of HMEC cells to grow in vitro as monolayers showed that expression of ER and EGFR is required for controlling tumor proliferative activity in vitro. Expression of ER protein made the growth of HMEC cells more difficult, while expression of EGFR protein made their growth in vitro easier. Phenotypic characteristics of floating HMEC cells were found to be different from those grown on cover slips as adherent cultures, suggesting a selective growth of HMEC cells of a specific phenotype in culture. Cultured HMEC cells in subsequent passages showed a decrease in their proliferative capacity, alterations in phenotypic characteristics and development of morphologic features of terminal differentiation, resulting in senescence.

Biomarkers, Tumor↗

Transverse colon conduit urinary diversion in patients treated with very high dose pelvic irradiation.

OBJECTIVE: To study the results of transverse colon conduit urinary diversion in patients receiving very high dose pelvic irradiation (> or = 65 Gy). PATIENTS AND METHODS: Records were reviewed for 30 such patients who underwent transverse colon conduit as a primary form of urinary diversion between January 1986 and June 1992. Most of the conduits were constructed using refluxing ureterocolic anastomoses with stents. RESULTS: There was no operative mortality. Although the procedure was associated with a complication rate of 37% and a re-operation rate of 20%, there were no bowel or urinary anastomotic leaks. The operation could be safely performed on patients with renal failure, with 83% of such patients showing normal or improved serum creatinine levels post-operatively. CONCLUSION: The advantages of transverse colon conduit urinary diversion are the use of non-irradiated bowel and ureters for diversion. We recommend it as a primary form of urinary diversion in these high risk cases.

Adult↗

Intravesical formalin for hemorrhagic cystitis following irradiation of cancer of the cervix.

OBJECTIVE: To determine the effectiveness of intravesical formalin instillation in hemorrhagic cystitis following irradiation of cancer of the cervix. METHOD: Records were reviewed for 35 patients with hemorrhagic radiation cystitis who underwent treatment with 1% (n = 22), 2% (n = 10), and 4% formalin (n = 4), using Fair's technique. RESULT: Complete response was seen in 31 patients (89%) and partial response in 3 patients (8%) after a single instillation. Minor complications were seen in 19 patients (54%). Major complications occurred in 11 patients (31%), with 5 cases requiring subsequent urinary diversion. One patient died of persistent bleeding and probable formalin toxicity. Hematuria recurred in 7 patients achieving complete response at a mean period of 8 months after treatment. A 1% solution was as effective in controlling hematuria as higher concentrations and was associated with significantly less morbidity. CONCLUSION: Intravesical instillation of 1% formalin is an effective treatment for intractable hematuria secondary to radiation cystitis.

Administration, Intravesical↗