Milk fat globule epidermal growth factor 8 (MFG-E8): a novel protein in the mammalian endometrium with putative roles in implantation and placentation.

OBJECTIVES: MFG-E8 is a novel endometrial protein with conserved functions in tissue remodeling and angiogenesis in non-uterine tissues. Our aims were: 1. To examine the presence of MFG-E8 protein in the human endometrium during the window of implantation, in human endometrial cell lines, in human placental tissue at different gestational ages, and in murine implantation sites during early gestation; and 2. To study the regulation of MFG-E8 mRNA expression in mice implantation sites. STUDY DESIGN: MFG-E8 protein and its receptor integrin αvß3 were detected by immunostaining in human endometrial biopsies obtained from normal volunteers, in human endometrial cell lines (epithelial: Ishikawa and HEC-1A, stromal: HESC, and endothelial: HEEC), in human products of conception from all trimesters of gestation, and in murine implantation and inter-implantation sites dissected on days 5 and 8 post-coitus. MFG-E8 gene expression was assessed by RT-PCR. MAIN OUTCOME MEASURES: Immunohistochemical determination of MFG-E8 in endometrium and products of conception as well as relative MFG-E8 mRNA expression in mice implantation sites. RESULTS: MFG-E8 protein was present almost exclusively in the epithelial compartment of human endometrium. It was also expressed in the cytotrophoblasts and syncytiotrophoblasts outlining chorionic villi of the human placenta at all trimesters of gestation, and in murine implantation sites. MFG-E8 mRNA was significantly up-regulated in murine implantation sites and with increased gestational age. CONCLUSIONS: MFG-E8 expression in the endometrial epithelium as well as in chorionic villi suggests its possible role in endometrial reorganization during the receptive phase and in events related to normal pregnancy in mammals.

A novel mechanism for chaperone-mediated telomerase regulation during prostate cancer progression.

Telomerase activity has been detected in >85% of all malignant human cancers, including 90% of prostate carcinomas. Using a well-characterized experimental prostate cancer system, we have found that telomerase activity is notably increased (>10-fold) during tumorigenic conversion. Expression profiles of the telomerase components (hTR and hTERT) revealed no substantive changes, which suggests a nontranscriptional mechanism for increased activity. Because the hsp90 chaperone complex functionally associates with telomerase, we investigated that relationship and found that along with telomerase activity, a number of hsp90-related chaperones are markedly elevated during transformation, as well as in advanced prostate carcinomas. Using the nontumorigenic cell protein extract as the source of telomerase, addition of purified chaperone components enhanced reconstitution of telomerase activity, which suggests a novel mechanism of increased telomerase assembly via a hsp90 chaperoning process during prostate cancer progression.

Pediatric hematuria and thin basement membrane nephropathy: what is it and what does it mean?

Hematuria is seen frequently in the pediatric population and may signal either benign or serious renal patholosis. A significant proportion of children with asymptomatic hematuria will have thin basement membrane nephropathy (TBMN), a benign disorder, yet there is little information about this entity outside the nephrology literature. This article is designed to provide an information base for pediatric practitioners to assist them in making appropriate decisions regarding diagnosis and care. A review of experience over a decade with 9 children with biopsy-proven TBMN, including follow-up to the present; is presented. In addition, review of literature regarding TBMN, Alport's and Berger's syndromes, which comprise the major clinical entities associated with asymptomatic pediatric hematuria, is presented. Each patient was evaluated for asymptomatic, documented and persistent hematuria. Renal biopsy was performed after clinical evaluation and follow-up. TBMN and Berger's disease (IgA nephropathy) are separable only by renal biopsy results; TBMN is benign and IgA nephropathy may be progressive, mandating referral to a nephrologist. The prognosis of TBMN is excellent.

Primary T-cell-rich B-cell lymphoma masquerading as a meningioma.

Primary dural lymphoma is rare, and few of the small number of cases reported to date have been classified using immunohistochemical techniques. To our knowledge, we report the first case of T-cell-rich B-cell lymphoma (diffuse mixed small cell and large cell) presenting as a solitary intracranial dural mass. Cytologic and frozen sections prepared during intraoperative consultation revealed a polymorphic population of lymphocytes suspicious for an inflammatory process. Permanent sections of the dura showed a diffusely infiltrating mass composed of mature lymphocytes peppered with large atypical lymphocytes. Immunohistochemical stains identified the small lymphocytes as T cells (CD3 and CD43) and the large atypical lymphocytes as B cells (CD20). Evidence of rearranged immunoglobulin heavy-chain genes demonstrated B-cell monoclonality. Differentiating between inflammatory and neoplastic lymphocytic masses of the dura obviously has important therapeutic and prognostic significance and may require immunohistochemical and molecular techniques.

Asymptomatic gross hematuria followed by persistent microhematuria.

A case of a previously healthy, 13-year-old male with IgA nephropathy is presented in order to illustrate clinical onset and differential diagnosis of this rather common clinical entity. The laboratory and histopathological diagnosis is illustrated and discussed, as well, together with a brief discussion of possible pathogenesis. In this disorder, in which approximately 11% of affected patients experience spontaneous remission, future development of molecular probes to determine prognosis is of great importance.

Central nervous system leiomyosarcoma in patients with acquired immunodeficiency syndrome. Report of two cases.

Leiomyosarcomas (LMSs) of the central nervous system are extremely rare; however, they are becoming more prevalent in immunocompromised patients. The authors present the cases of two patients with acquired immunodeficiency syndrome: one with LMS of the thoracic vertebral body and the other with LMS originating from the region of the cavernous sinus. The epidemiological and histological characteristics of LMS and its association with latent Epstein-Barr virus are discussed, as well as the treatments for this neoplasm.

Intracranial extension of an eccrine porocarcinoma. Case report and review of the literature.

Eccrine porocarcinoma is a rare malignant tumor of the true sweat gland. It commonly presents in the lower extremities with lymphatic metastasis. The authors describe the clinical presentation, radiographic evidence, operative discoveries, and pathological findings in a patient with an eccrine porocarcinoma involving the soft tissue of the occiput, which had eroded through the cranium. A review of the literature failed to reveal any other such case. The discussion includes the epidemiology, pathogenesis, treatment, and outcome of eccrine porocarcinomas. The six reported cases of scalp eccrine tumors are reviewed.

Molecular detection of JC virus in embalmed, formalin-fixed, paraffin-embedded brain tissue.

Embalmed tissues are adequate for the detection of JC virus in lesions of progressive multifocal leukoencephalopathy (PML) by immunohistologic and molecular methods. JC virus was readily detected in embalmed brain tissue using immunohistochemistry (IHC), in situ hybridization (ISH), and the polymerase chain reaction (PCR). Two brains were removed from bodies that had been embalmed at least 24 h prior to autopsy. They were subsequently post fixed in 10% buffered formalin for 10-14 days before dissection and molecular studies were performed. Though these techniques are not novel, their use in embalmed tissues is. Routine embalming should not eliminate these diagnostic procedures from consideration.