Biomedical subjects

B J Quade

Publications and source records attributed to B J Quade.

26 records · Page 2Linked to original sources

PubMed1997

Disseminated peritoneal leiomyomatosis. Clonality analysis by X chromosome inactivation and cytogenetics of a clinically benign smooth muscle proliferation.

Disseminated peritoneal leiomyomatosis (DPL, leiomyomatosis peritonealis disseminata) is a rare condition in which multiple histologically benign smooth muscle tumorlets diffusely stud peritoneal and omental surfaces in females, predominantly of reproductive age. Although the distribution of these lesions suggests a metastatic process, DPL generally has a benign clinical course and has been regarded as a metaplastic process. We assessed clonality of 42 tumorlets and 15 normal tissues from four females with DPL by analyzing X chromosome inactivation as indicated by the methylation status of the androgen receptor gene (HUMARA). In each of the four patients, the same parental X chromosome was nonrandomly inactivated in all tumorlets, consistent with a metastatic unicentric neoplasm, or alternatively, selection for an X-linked allele in clonal multicentric lesions. Anomalous demethylation of the marker for X inactivation (HUMARA) was associated with loss of heterozygosity for markers spanning the X chromosome, or monosomy X, in part of one leiomyomatous lesion. Biallelic demethylation of the HUMARA microsatellite polymorphism was also found in one intramural leiomyoma. Two of six DPL lesions karyotyped had cytogenetic abnormalities involving chromosomes 7, 12, and 18, suggesting a pathogenesis in common with uterine leiomyomas.

Adult↗

PubMed1995

Pathology, cytogenetics and molecular biology of uterine leiomyomas and other smooth muscle lesions.

Uterine smooth muscle tumors are common and pose a significant public health problem for women of reproductive age. Although most uterine smooth muscle tumors are benign, pathologic diagnosis of the infrequent malignant leiomyosarcoma is important for clinical management and prediction of clinical outcome. Pathologic criteria for diagnosing malignancy in uterine smooth muscle tumors and studies of their validity are reviewed. Advances in the cytogenetic and molecular biologic study of uterine leiomyomas and their variants are being made which may ultimately change our understanding of their pathobiology, diagnosis, and potentially, their treatment.

Chromosome Aberrations↗

PubMed1993

Meningeal carcinomatosis from transitional cell carcinoma of the bladder.

Response rates of over 50% can be achieved in patients with metastatic transitional cell carcinoma of the bladder treated with cisplatin-based chemotherapy. With prolonged survival, intraparenchymal brain metastases may occur in as many as 12% of patients who received methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy. Meningeal carcinomatosis from urothelial cancer is rare, however. A 71-year-old man, with metastatic, transitional cell carcinoma of the bladder, attained an excellent partial response to M-VAC chemotherapy. He subsequently presented with an acute confusional state 6 months after diagnosis. Head computed tomographic studies were nondiagnostic. Gadolinium-enhanced magnetic resonance images (MRI), however, demonstrated multifocal 1-cm nodules in the brain parenchyma and enhancement of the meninges. Meningeal carcinomatosis was confirmed by lumbar puncture. Records of 40 patients with advanced transitional cell carcinoma of the bladder treated with chemotherapy between 1977 and 1992 at a cancer center were reviewed retrospectively for the occurrence of documented meningeal carcinomatosis, intraparenchymal brain metastases, or both. Among 13 responders, only 1 other patient, a 64-year-old man, was identified who had minimal metastatic disease and attained a complete response to methotrexate and cisplatin. The patient relapsed 2 years after response, with cerebellar metastases and meningeal carcinomatosis. Central nervous system (CNS) metastases in patients with transitional cell carcinoma of the bladder are unusual. Although parenchymal brain metastases may be more common after prolonged remissions induced by combination chemotherapy, meningeal carcinomatosis remains uncommon. MRI may be a useful adjunct in the diagnosis of CNS metastases. A high index of clinical suspicion for the occurrence of CNS metastases from transitional cell carcinoma is encouraged.

Aged↗

PubMed1992

Prenatal sonography in trisomy 9.

Two cases of trisomy 9 are presented with the description of the prenatal sonographic findings prompting prenatal cytogenetics evaluation. The characteristic sonographic abnormalities included structural heart defects; limb, renal, and facial anomalies; and intrauterine growth retardation. The clinical course and cytogenetic and autopsy finding are described.

Adult↗

PubMed1991

Cell surface molecules that bind fibronectin's matrix assembly domain.

The assembly of fibronectin into disulfide cross-linked extracellular matrices requires the interaction of mesenchymal cells with two distinct sites on fibronectin, the Arg-Gly-Asp cell adhesive site and an amino-terminal site contained within the first five type I homologous repeats (Quade, B. J., and McDonald, J. A. (1988) J. Biol. Chem. 263, 19602-19609). Proteolytically derived 29-kDa fragments of fibronectin (29kDa) containing these repeats bind to monolayers of cultured fibroblasts and inhibit fibronectin matrix assembly. The cell surface molecules interacting with fibronectin's 29-kDa matrix assembly domain have resisted purification using conventional methods such as affinity chromatography. Accordingly, in order to identify molecules which bind this fragment, 125I-labeled 29kDa was allowed to bind to fibroblast monolayers and chemically cross-linked to the cell surface with bis(sulfosuccinimidyl) suberate. Extraction of the cross-linked cell layer yielded radiolabeled complexes of 56, 150, and 280 kDa. Formation of these cross-linked complexes was specifically inhibited by the addition of excess unlabeled 29kDa but was unaffected by the presence of fibronectin fragments containing other type I repeats outside of the 29kDa matrix assembly domain. The cross-linked complexes were insoluble in nondenaturing detergents but soluble when denatured and reduced, suggesting that 29kDa may be cross-linked to components of the pericellular matrix. Immunoprecipitation of cross-linked cell extracts with a polyclonal antibody to fibronectin that does not recognize the amino terminus demonstrate that the 280-kDa band contains 29kDa cross-linked to fibronectin present on the cell surface. Formation of the 150-kDa complex was inhibited by EDTA, suggesting that divalent cations are required for its formation. Although the molecular mass and divalent cation requirement suggest that the 150-kDa complex may be related to an integrin, this complex was not immunoprecipitated by polyclonal antibodies generated to the alpha 5 beta 1 integrin fibronectin receptor.

Animals↗

PubMed1988

Fibronectin's amino-terminal matrix assembly site is located within the 29-kDa amino-terminal domain containing five type I repeats.

Fibronectin is organized into disulfide cross-linked, insoluble pericellular matrix fibrils by fibroblasts in vitro. Two sites, the Arg-Gly-Asp-Ser-containing cell attachment domain and a site located in the first 70 kDa of fibronectin, are required for matrix assembly. The first 70 kDa of fibronectin contain two structural motifs termed type I and type II homologies, which are repeated nine and two times, respectively. Previous work has implicated the amino-terminal region and the carboxyl terminus containing three type I repeats in matrix assembly, suggesting that type I repeats possess binding activity essential for fibronectin matrix assembly. To test this hypothesis, we developed a sensitive capture immunoassay to quantify insoluble matrix fibronectin and tested a panel of fibronectin fragments, containing all of the type I repeats found in the intact protein, for their ability to inhibit matrix assembly. Only fragments containing the first five type I repeats inhibited fibronectin matrix assembly, although sequences carboxyl-terminal to this domain enhanced this activity. Additional evidence for the specific recognition of the amino-terminal type I repeats by matrix assembling cells was found when the reversible, detergent-sensitive binding of a 125I-labeled fragment containing the first five type I repeats (29 kDa) to cell monolayers was studied. Only monolayers of cell lines that incorporate fibronectin into a fibrillar matrix specifically bound 125I-labeled 29 kDa. Binding of the radiolabeled amino-terminal fragment to matrix-forming cells was inhibited by unlabeled fragments containing the first five type I repeats but not by unlabeled fragments containing the remaining seven type I repeats. Matrix assembly is therefore not a generalized property of type I repeats. Rather, a critical site is located within the first 29 kDa of fibronectin.

Amino Acid Sequence↗

PubMed1987

Fibronectin's cell-adhesive domain and an amino-terminal matrix assembly domain participate in its assembly into fibroblast pericellular matrix.

Fibroblasts organize the modular cell-adhesive glycoprotein fibronectin into a highly structured pericellular matrix by poorly understood mechanisms. Previous studies implicated an amino-terminal domain in matrix assembly and suggested that fibronectin's cell-adhesive domain and the corresponding fibroblast receptor were not involved in this process. To further elucidate the fibronectin region(s) involved in matrix assembly, we mapped a library of proteolytic fragments and antibodies to various fibronectin domains. The fragments and antibodies were used to probe the role of fibronectin's amino-terminal and cell-adhesive domains in a fibroblast matrix assembly assay. We found that fibronectin fragments including the first 25-kDa sequence of fibronectin and antibodies to amino-terminal domains inhibited pericellular matrix assembly. Polyclonal antibodies to the 40-kDa collagen binding domain following the 25-kDa amino-terminal domain also inhibited matrix assembly. However, collagen binding is not required for matrix assembly as neither monoclonals blocking collagen binding nor purified collagen binding domains themselves inhibited matrix assembly. Therefore, the amino-terminal region of fibronectin contains a site important in matrix assembly, and most activity is present in the first 25-kDa of fibronectin. Fibronectin's cell-adhesive domain and the fibroblast receptor binding to this domain also play an important role in fibronectin matrix assembly. Apart from a monoclonal antibody to the amino-terminal domain, only monoclonal antibodies binding to fibronectin's cell-adhesive domain and inhibiting cell adhesion also inhibited matrix assembly. In addition a 105-kDa fragment containing the cell-adhesive domain inhibited matrix assembly. We conclude that at least two discrete and widely separated sites in fibronectin with different binding properties--the carboxyl-terminal fibroblast cell-adhesive domain and an amino-terminal matrix assembly domain localized primarily within the first 25 kDa--are required for fibronectin pericellular matrix assembly by fibroblasts. Fibronectin's cell-adhesive domain and its cell surface-receptor complex appear to be involved in the matrix assembly process prior to a step involving the amino-terminal domain. We believe that this step is likely to be the initiation of cell-associated fibronectin fibril formation by the fibronectin-adhesive-receptor complex.

Amino Acid Sequence↗

PubMedDate not supplied

Adenomyosis demonstrates increased expression of the basic fibroblast growth factor receptor/ligand system compared with autologous endometrium.

OBJECTIVES: Basic fibroblast growth factor (bFGF) is an angiogenic growth factor present in human endometrium and myometrium. Women with leiomyoma-related abnormal uterine bleeding have local dysregulation of bFGF and its type 1 receptor (FGF-R). This study was designed to evaluate if adenomyosis expresses bFGF and FGF-R, and if present, to compare bFGF and FGF-R expression in adenomyosis and autologous endometrium. DESIGN: Menopausal uteri containing endometrium and adenomyosis were analyzed using immunohistochemistry with monoclonal antibodies specific for bFGF, FGF-R, and proliferating cell nuclear antigen (PCNA), a marker of cellular proliferation. The expression and intensity of staining for bFGF, FGF-R, and PCNA were evaluated in the glandular epithelium and stroma of adenomyosis and endometrium. RESULTS: Glandular epithelial staining was significantly greater in adenomyosis compared with autologous endometrium for bFGF and FGF-R. Stromal staining for bFGF and PCNA was significantly increased in adenomyosis compared with autologous endometrium. CONCLUSIONS: Upregulation of the bFGF receptor/ligand system and increased cellular proliferation in adenomyosis may contribute to the pathogenesis of abnormal uterine bleeding associated with adenomyosis.

Aged↗