Biomedical subjects
E Shapiro
Publications and source records attributed to E Shapiro.
Uroplakin and androgen receptor expression in the human fetal genital tract: insights into the development of the vagina.
PURPOSE: Although a dual origin of the vagina has been popularized, other theories support a müllerian or wolffian duct origin or various combinations of these structures and the urogenital sinus. Uroplakins are specialized membrane proteins of the urothelial plaque, constituting the asymmetrical unit membrane of the bladder, and represent specific molecular markers of urothelial differentiation. We hypothesize that the epithelium of the dorsal wall of the urogenital sinus is involved in the formation of the sinovaginal bulbs and will express uroplakins. In addition, localization of the androgen receptor and its temporal expression during development may in part explain the varied effects of androgens on the lower female genital tract in congenital adrenal hyperplasia. MATERIALS AND METHODS: Lower genitourinary tracts from 4 human female fetuses (9 to 18 weeks) were serially sagittally sectioned. Representative sections were stained with hematoxylin and eosin, rabbit antibodies against panuroplakin and antibodies to the androgen receptor. RESULTS: At 9 weeks of gestation the urogenital sinus showed evidence of evagination and the formation of the sinovaginal bulbs. The urothelium of the entire urogenital sinus expressed uroplakins including the region of the dorsal wall involved in evagination and formation of the sinovaginal bulbs. The müllerian ducts were in direct contact with the area of urogenital sinus evagination but were not in continuity with the sinus. Androgen receptors were expressed in the epithelium and the stroma of the urogenital sinus, sinovaginal bulbs, and müllerian and wolffian ducts. By 14 weeks androgen receptor expression was almost absent in the urothelium of the urogenital sinus, and the epithelium and surrounding stroma of the lower vagina and müllerian ducts. CONCLUSIONS: The area of evagination of the urogenital sinus expresses uroplakins, is involved in the formation of the sinovaginal bulbs and further substantiates the urogenital sinus origin of the lower vagina. Since testosterone inhibits formation of the lower vagina, the timing of exposure to systemic testosterone in congenital adrenal hyperplasia will determine the phenotypic appearance of the external genitalia and effect of testosterone on the development of the lower genital tract. If exposure to testosterone occurs after 12 weeks only clitoromegaly occurs. Androgen receptor is absent in the urogenital sinus urothelium, vaginal epithelium and müllerian ducts by 14 weeks, suggesting that these tissues become androgen insensitive and vaginal development will proceed normally after that critical time.
Viral strain identification in varicella vaccinees with disseminated rashes.
BACKGROUND: Approximately 15% of recipients of live attenuated varicella vaccine may develop mild breakthrough varicella months to years after immunization. Although some vaccinees will develop zoster, it is less common in recipients of vaccine than in those who have had natural varicella. OBJECTIVE: To determine the varicella-zoster virus (VZV) strain responsible for breakthrough varicella and zoster in recipients of varicella vaccine. METHODS: A PCR assay capable of distinguishing wild-type from vaccine strain VZV was performed on samples from skin lesions from vaccinees with breakthrough varicella and zoster. RESULTS: All of 57 vaccinees with breakthrough varicella, clinically diagnosed on the basis of a generalized maculopapular or vesicular rash, in which there was amplifiable DNA [corrected], had wild-type VZV infection based on analysis of viral DNA. The Oka vaccine strain of VZV was not identified in any of these cases. In contrast, in 32 patients with zosteriform rashes, the vaccine strain was identified in 22 samples, and the wild-type strain was identified in 10 samples. CONCLUSIONS: Wild-type virus was identified in all generalized rashes occurring after the immediate 6-week postvaccination period. When reactivation of vaccine strain occurred, it presented as typical zoster. We find no evidence that reactivation of vaccine virus occurs with the clinical picture of generalized rash.
Office laboratory procedures, office economics, parenting and parent education, and urinary tract infection.
We again review four areas of interest to office-based pediatricians: office laboratory procedures, office economics, parenting and patient education, and urinary tract infections. Sean Elliott provides an update on the Clinical Laboratories Improvement Amendments (CLIA) and their impact of office practice. Eve Shapiro reviews office economics, focusing on measuring quality of care, use of performance data, costs of new technologies, and the impact of managed care on the medical marketplace. John Walter offers an update on parenting and parent education, with approaches to counseling families about overuse of antibiotics, teen pregnancy, hyperactivity, violence, and asthma. Richard Wahl reviews the recent research on urinary tract infection, with special attention paid to office diagnosis and management, longitudinal studies of children with urinary tract infections, and the controversy surrounding the American Academy of Pediatrics Task Force on Circumcision report.
Immunohistochemical localization of cyclooxygenase-1 and cyclooxygenase-2 in the human fetal and adult male reproductive tracts.
The first rate-limiting step in the conversion of arachidonic acid to PGs is catalyzed by cyclooxygenase (Cox). Two isoforms of Cox have been identified, Cox-1 (constitutively expressed) and Cox-2 (inducible form), which are the products of two different genes. In this study we describe the immunohistochemical localization of Cox-1 and -2 in the human male fetal and adult reproductive tracts. There was no Cox-1 expression in fetal samples (prostate, seminal vesicles, or ejaculatory ducts), and only minimal expression in adult tissues. There was no expression of Cox-2 in the fetal prostate. In a prepubertal prostate there was some Cox-2 expression that localized exclusively to the smooth muscle cells of the transition zone. In adult hyperplastic prostates, Cox-2 was strongly expressed in smooth muscle cells, with no expression in the luminal epithelial cells. Cox-2 was strongly expressed in epithelial cells of both fetal and adult seminal vesicles and ejaculatory ducts. The Cox-2 staining intensity in the fetal ejaculatory ducts during various times of gestation correlated with previously reported testosterone production rates by the fetal testis. These data indicate that Cox-2 is the predominant isoform expressed in the fetal male reproductive tract, and its expression may be regulated by androgens. The distinct cell type-specific expression patterns of Cox-2 in the prostate (smooth muscle) vs. the seminal vesicles and ejaculatory ducts (epithelium) may reflect the different roles of PGs in these tissues.
Reaching a federal/provincial consensus on home care.
This commentary agrees with Dr. MacAdam that the time has come to implement a national home-care program based on principles similar to those that underpin the Canada Health Act. It also agrees with the general thrust of the proposed vision. However, it disputes some of the grounds on which Dr. MacAdam's vision is based and offers alternative perspectives on key aspects of home care. It concludes with a discussion of the issues that will influence the prospects of reaching a federal/provincial consensus on a Canadian home-care program.
Comment on the article "can immunization precipitate connective tissue disease? Report of 5 cases of systemic lupus erythematosus and review of the literature".
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Community and long-term facility care in Canada.
By 1969, federal/provincial agreements had resulted in universally-insured access to hospital and medical services for all Canadians. In the absence of similar agreements for community and long-term care, each province has designed, implemented, and modified its own policies and programs during the last three decades. However, the communal values and the universal access to hospital and medical services which underpinned the national health plan influenced these policies and programs. Over time, the provincial programs have become more similar to each other but significant differences remain. However, all the provincial programs combine the assessment and delivery of short- and long-term community care and almost all combine the assessment of need for community care with that for long-term facility care placement. This article examines the development and changes in the community care and long-term facility care sectors in Canada over the recent past. Despite financial constraints which have resulted in the downsizing of hospitals and reductions in the ratio of long-term beds to the population aged 75 and over, community care budgets have increased substantially during this time. The article also discusses the major issues now confronting Canadian policy-makers and planning in regards to these programs and explores the potential impact of factors such as changes in funding and the organization and delivery of other health care services on long-term care.
Prenatal hydronephrosis-are voiding cystourethrograms necessary?
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Strategies for the Management of Exstrophy, Nonpalpable Testis, Hydronephrosis: Highlights From the Annual Meeting of the American Academy of Pediatrics Section on Urology October 9-12, 1999, Washington, DC.
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Update on fetal surgery: highlights from the society for pediatric urology 49th annual meeting april 29, 2000, atlanta.
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Cryptorchidism and overactive bladder.
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Urothelium-specific expression of an oncogene in transgenic mice induced the formation of carcinoma in situ and invasive transitional cell carcinoma.
Although many genetic alterations are known to be associated with human transitional cell carcinoma (TCC) of the urinary bladder, relatively little is known about the roles of these molecular defects, singular or in combination, in bladder tumorigenesis. We have developed a transgenic mouse model of bladder tumorigenesis using a 3.6-kb promoter of uroplakin II gene to drive the urotheliums-specific expression of oncogenes. In this study, we demonstrate that transgenic mice bearing a low copy number of SV40T transgene developed bladder carcinoma in situ (CIS), whereas those bearing high copies developed CIS as well as invasive and metastatic TCCs. These results indicate that the SV40T inactivation of p53 and retinoblastoma gene products, defects frequently found in human bladder CIS and invasive TCCs, can cause the aggressive form of TCC. Our results also provide experimental proof that CIS is a precursor of invasive TCCs, thus supporting the concept of two distinct pathways of bladder tumorigenesis (papillary versus CIS/invasive TCC). This transgenic system can be used for the systematic dissection of the roles of individual or combinations of specific molecular events in bladder tumorigenesis.
New concepts on the normal and abnormal developing bladder.
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New concepts of histological changes in experimental augmentation cystoplasty: insights into the development of neoplastic transformation at the enterovesical and gastrovesical anastomosis.
PURPOSE: To our knowledge the pathogenesis of malignancy associated with ileal cystoplasty, ureterosigmoidostomy and ileal conduits is currently unknown. To gain further insights into the mechanism of neoplastic transformation we studied histological changes in a canine augmentation cystoplasty model. MATERIALS AND METHODS: Enterocystoplasty and gastrocystoplasty were performed using a 5 to 7 cm. patch of ileum in 8 dogs and gastric antrum in 6. Specimens were harvested 4 months postoperatively. Representative 3 microm sections of the enterovesical and gastrovesical junctions were stained with hematoxylin and eosin. Uroplakin expression was assessed using an indirect peroxidase method subjected to double staining with alcian blue and periodic acid-Schiffreagent. RESULTS: The bladder portion of the augmentation cystoplasty had 3 to 4 stratified cell layers covered with a distinctive umbrella cell layer. Strong uroplakin staining was visible in all cell layers except the basal layer. At the enterovesical and gastrovesical junctions 6 to 10 layers of hyperplastic, urothelial appearing cells covered the glandular epithelium of the ileal and gastric segments. These cells expressed uroplakins. At this junction zone there was a marked decrease of underlying enteric glands, which had atrophied in proportion to the degree of urothelial hyperplasia. Double staining of uroplakin stained sections with alcian blue and periodic acid-Schiff reagent revealed mucosubstances in hyperplastic urothelial cells covering the enteral segments, indicating that the cells co-expressed uroplakins and mucins. CONCLUSIONS: Histological changes in this experimental canine model of augmentation cystoplasty indicated that the overgrowth of hyperplastic transitional epithelium develops at the enterovesical and gastrovesical junctions. These cells express not only uroplakins, but also mucosubstances. Our results suggest that the migrated hyperplastic urothelial cells have undergone changes characteristic of the enteric and gastric epithelium, which may have important implications in the pathogenesis of malignancy in bladder augmentations.
Revisiting the Manitoba Centre for Health Policy and Evaluation and its population-based health information system.
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From research to policy: what have we learned?
The Manitoba Centre for Health Policy and Evaluation has now had eight years of experience as an academic research unit interfacing with policymakers. Most of our research has focused on the determinants of health and on the delivery of health care from a population perspective. Each project that we have undertaken has made its own contribution and reinforced or built on the contribution of others. By communicating closely with policymakers at all levels, while maintaining an arm's-length relationship and the right of publication, MCHPE acts as a knowledgeable non-stakeholder with a commitment to inform the broader public.
Unusual case of diarrhea in a 19-month-old girl.
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