Biomedical subjects

Donald J McCrann

Publications and source records attributed to Donald J McCrann.

4 recordsLinked to original sources

PubMed2007

Alphav beta6 integrin regulates renal fibrosis and inflammation in Alport mouse.

The transforming growth factor (TGF)-beta-inducible integrin alpha v beta6 is preferentially expressed at sites of epithelial remodeling and has been shown to bind and activate latent precursor TGF-beta. Herein, we show that alpha v beta6 is overexpressed in human kidney epithelium in membranous glomerulonephritis, diabetes mellitus, IgA nephropathy, Goodpasture's syndrome, and Alport syndrome renal epithelium. To assess the potential regulatory role of alpha v beta6 in renal disease, we studied the effects of function-blocking alpha v beta6 monoclonal antibodies (mAbs) and genetic ablation of the beta6 subunit on kidney fibrosis in Col4A3-/- mice, a mouse model of Alport syndrome. Expression of alpha v beta6 in Alport mouse kidneys was observed primarily in cortical tubular epithelial cells and in correlation with the progression of fibrosis. Treatment with alpha v beta6-blocking mAbs inhibited accumulation of activated fibroblasts and deposition of interstitial collagen matrix. Similar inhibition of renal fibrosis was observed in beta6-deficient Alport mice. Transcript profiling of kidney tissues showed that alpha v beta6-blocking mAbs significantly inhibited disease-associated changes in expression of fibrotic and inflammatory mediators. Similar patterns of transcript modulation were produced with recombinant soluble TGF-beta RII treatment, suggesting shared regulatory functions of alpha v beta6 and TGF-beta. These findings demonstrate that alpha v beta6 can contribute to the regulation of renal fibrosis and suggest this integrin as a potential therapeutic target.

Animals↗

PubMed2005

Vascular smooth muscle cell polyploidization involves changes in chromosome passenger proteins and an endomitotic cell cycle.

Vascular smooth muscle cell polyploidization occurs during normal development and is enhanced under physiologic stress, but the mechanism of this cell cycle has not been explored. We show via time-lapse video imaging and immunofluorescence analyses that primary vascular smooth muscle cells (VSMC) undergo an endomitotic-type cell cycle, including a normal progression through part of mitosis. Mononuclear polyploid cells are generated by defects in sister chromatid separation and/or segregation, and cellular binucleation occurs by reversal of cytokinesis. To obtain further leads to regulators involved, we examined the chromosomal passenger proteins, Aurora B, inner centromere protein and Survivin, and concluded that Aurora B and inner centromere protein are normally colocalized in centromeres, the midzone, and the midbody during mitosis. Survivin, however, is dim and diffused; it does not colocalize with either Aurora B or inner centromere protein in VSMC, which could account for defects in sister chromatid separation and/or segregation and reversal of cytokinesis. In accordance with the reported dependency of Aurora B activity on Survivin, the Aurora B substrate, vimentin, is not phosphorylated during cytokinesis. Finally, the data show that ectopically expressed Survivin inhibits polyploidization in vascular smooth muscle cells. Hence, aberrant chromosome passenger protein activity and endomitosis are associated with VSMC polyploidization.

Animals↗

PubMed2003

Culture-based group B streptococcal screening. Adherence to current guidelines.

OBJECTIVE: To examine the ability of a universal screening strategy to identify and treat group B Streptococcus-positive women with intrapartum antibiotics. STUDY DESIGN: Charts were reviewed on all patients delivering at > or = 36 weeks of gestation as to the presence of culture results, whether or not antibiotics were ordered and when they were given relative to the time of delivery. RESULTS: Approximately 95% of patients presenting at > or = 36 weeks had group B Streptococcus results available. Overall, 84% of culture-positive patients received chemoprophylaxis. Removal of the elective cesareans from the study population increased the percentage of positive patients receiving antibiotics to 94%. Ideal chemoprophylaxis, defined as delivering > or = 2 hours after receiving the recommended antibiotics, occurred 87% of the time. Failure to order appropriate antibiotics was the most frequent reason for not receiving chemoprophylaxis. CONCLUSION: Successful universal culturing followed by intrapartum chemoprophylaxis can be accomplished in a majority of cases. Failure to treat can occur (6%), and chemoprophylaxis may be less than ideal (13%) due to rapid labor and human error.

Adult↗

PubMed2002

Nonbilharzial bladder carcinoma complicating pregnancy: review of the literature.

UNLABELLED: The purpose of this review is to evaluate tumor presentation and characteristics, and maternal-fetal outcomes of pregnancies complicated by nonbilharzial bladder carcinoma. The mean age of the patients was 29.5 years (range = 18-40). Symptoms and diagnosis occurred after the first trimester in 20 (83%) and 22 (92%) cases, respectively. Presenting complaints included painless gross hematuria [N = 12 (50%)], vaginal bleeding [N = 7 (29%)], dysuria [N = 2 (8.4%)], abdominal pain [N = 2 (8.4%)], and 1 instance each of urgency, frequency, recurrent cystitis, and no symptoms. Tumors were initially identified by ultrasound [N = 12 (50%)], cystoscopy [N = 11 (46%)], and intravenous urography [N = 1 (4.5%)]. Transitional cell carcinoma was found in 17 (74%), adenocarcinoma in 5 (22%), and squamous cell carcinoma in 1 (4.5%) patient. Tumors did not favor a specific bladder location, tended to be low grade [8 (40%) = grade 1, 7 (35%) = grade 2; 5 (21%) = grade 3], and noninvasive [N = 19 (79%)]. Treatment was typically by transurethral resection (N = 18), but 3 women required radical cystectomy, 2 received radiation, 1 received chemotherapy, and 1 underwent partial cystectomy. Three (14%) women died of their disease and 3 (14%) fetuses were lost because of complications of cancer or its treatment. Bladder carcinoma in pregnancy can mimic cystitis or obstetric hemorrhage and should be considered when evaluations for these conditions are negative. Routine ultrasound evaluation of the bladder in these patients may improve the diagnostic yield. Pregnancy is not a contraindication to treating most forms of bladder cancer. TARGET AUDIENCE: Obstetricians and Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to list the various types of bladder cancers, to describe the presenting symptoms in a patient with a bladder cancer, and to outline the work up and treatment strategies for bladder cancer.

Carcinoma, Transitional Cell↗