Bladder carcinoma surgical pathology report adequacy.
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Biopsy↗
Biomedical subjects
J N Eble
Publications and source records attributed to J N Eble.
A symposium on controversies in the pathology of transitional cell carcinomas of the urinary bladder. Part I.
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Carcinoma, Transitional Cell↗
Differential cellular and subcellular expression of the human multifunctional apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme.
The multifunctional mammalian apurinic/apyrimidinic endonuclease (APE) is responsible for the repair of apurinic/apyrimidinic sites in DNA. In addition, this enzyme has been shown to function as a redox factor facilitating the DNA-binding capability of JUN and FOS, as well as numerous other transcription factors through the alteration of the transcription factor redox state. Biochemical studies of organ homogenates have shown that APE is present in the different tissues studied at similar concentrations. The present study examines the immunohistochemical distribution of APE in several organs and demonstrates new and unexpected patterns of cellular and subcellular localization of this enzyme. In the hippocampus, the APE protein was highly expressed in neurons of the dentate gyrus and regions CA3 and CA4, and unexpectedly, the staining was primarily cytoplasmic. AP endonuclease immunoreactivity in the cerebellum was found in the granule and Purkinje cells, both cytoplasmic and nuclear. APE staining of the hypoglossal nucleus of the brainstem, where motor neurons that control tongue movement reside, showed reactivity in the cytoplasmic Nissl substance. Skin, liver, and duodenum demonstrated nuclear staining; however, in the duodenum, only the enterocyte nuclei of the proximal villus and the crypts of Lieberkuhn were stained, with no staining of the distal villus. These results suggest that APE has different regulatory and functional roles in different cells and organs of the body. This study shows the importance of correlating in vitro findings in tissue culture cells with the organism as a whole. The cytoplasmic staining seen in parts of the brain and in liver suggests that there may be additional functions for the APE yet to be described.
Autopsy↗
Differential cellular expression of the human MSH2 repair enzyme in small and large intestine.
The human MSH2 (hMSH2) protein is responsible for the initial recognition of mismatched nucleotides during the postreplication mismatch repair process. Loss of hMSH2 function has been demonstrated to lead to the accumulation of replication errors, resulting in a mutator phenotype, which may be responsible for the multiple mutations required for multi-stage carcinogenesis. Alterations of the hMSH2 gene has been linked to approximately 60% of hereditary nonpolyposis colon cancer cases. Colon tumors in hereditary nonpolyposis colon cancer patients originate within benign preneoplastic adenomas and display replication errors in the form of microsatellite instability. The aim of this study was to investigate the cellular expression of the hMSH2 protein in cells of the large and small intestines. Using antibody specific for hMSH2, we have determined that this protein is highly expressed in cells of the crypts of Lieberkühn that are undergoing rapid renewal in both the ileum and colon. Proliferative perifibroblasts in the colon also showed significant presence of the hMSH2 protein. These results confirm the hypothesis that hMSH2 is expressed in highly proliferative cells of the gut, and mutations in this gene could, therefore, be expected to expedite the progression of adenoma to carcinoma in this tissue.
Animals↗
Radiofrequency catheter ablation of the atria reduces inducibility and duration of atrial fibrillation in dogs.
BACKGROUND: The purpose of this study was to prevent induction of sustained atrial fibrillation (AF) by radiofrequency catheter ablation (RFCA) of the atria in an open-chest canine model. METHODS AND RESULTS: In dogs randomized to acute studies, RFCA of the atria was performed after reproducible induction of sustained AF (lasting > 30 minutes) with burst stimulation or premature atrial pacing and perpetuation by low level cervical vagal stimulation or IV infusion of methacholine. Additionally, in four dogs, the long-term effectiveness of RFCA was assessed 7 to 21 days after ablation. Continuous discrete transmural lesions were produced with radiofrequency energy pulses (20 to 40 W for 60 seconds) delivered to five atrial epicardial sites and endovascularly to the coronary sinus wall. RFCA electrically isolated regions of the atria that became dissociated from the nonisolated parts. Atrial RFCA markedly attenuated vagally induced shortening of effective refractory period (ERP) at both isolated and nonisolated test sites located in the left and right atria (P < .001, n = 5). RFCA rendered noninducible sustained AF maintained by cervical vagal stimulation. The dose-response curve relating the dose of methacholine required to maintain AF was shifted down and to the right. AF was only inducible with high doses of methacholine. Atrial RFCA reduced the maximal sinus rate and prolonged the corrected sinus-node recovery time (P < .001, n = 6). However, RFCA did not affect atrial contractile function, AV-nodal ERP, or AV-nodal or His-Purkinje conduction times. In dogs in the chronic group, normal sinus rhythm and normal AV conduction were preserved and AF was only inducible with a high dose of methacholine. No atrial perforations resulted. CONCLUSIONS: RFCA in open-chest dogs produces partial vagal denervation and reduces the inducibility of AF.
Animals↗
Cost analysis of point-of-care laboratory testing in a community hospital.
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Clinical Laboratory Techniques↗
Spermatocytic seminoma.
Spermatocytic seminoma is a rare testicular neoplasm that occurs only in adults (range, 25 to 87 years; mean, 54). It has no ovarian homologue and is found only in descended testes. It is not associated with other types of germ cell neoplasia. Orchiectomy is curative in virtually all cases; of more than 200 known cases, only one has metastasized. In a dozen cases sarcomas have arisen in the testes in association with spermatocytic seminoma; most of these patients have died of metastatic sarcoma after short intervals. The gross appearance is characteristically edematous or gelatinous and more than half the tumors have been more than 5 cm in diameter. Microscopically, they are composed of sheets of small, medium, and large cells with spherical nuclei. The chromatin is dense in the small cells and filamentous in the medium and large ones. The cytoplasm is eosinophilic to amphophilic and lacks glycogen. It is not associated with intratubular germ cell neoplasia of the undifferentiated type. Analyses of DNA content have failed to show haploid populations and the lectin binding does not show maturation toward spermatocytes. Differing from seminoma in essentially all characteristics, it is not a variant of seminoma.
Adult↗
prostatic xanthoma: a mimic of prostatic adenocarcinoma.
Xanthoma is a localized collection of cholesterol-laden histiocytes that is usually idiopathic, but may be seen in patients with hyperlipidemia. We report seven cases of xanthoma involving the prostate, including one arising in a patient with mild hyperlipidemia. Prostatic xanthoma appeared as a solitary microscopic lesion in the peripheral zone (six cases) or transition zone (one case). One needle biopsy specimen with xanthoma was initially interpreted as well-differentiated adenocarcinoma with a clear cell (hypernephroid) pattern, but immunohistochemical studies revealed the histiocytic nature of the proliferation. Five cases (three needle biopsy specimens and two retropubic prostatectomy specimens) contained a solitary xanthoma adjacent to foci of adenocarcinoma. Another xanthoma was present in a transurethral resection specimen with nodular hyperplasia. Although unusual, xanthoma should be considered in the differential diagnosis of clear cell adenocarcinoma and other clear cell proliferations of the prostate, particularly in limited tissue samples, such as from needle biopsies and transurethral resections.
Adenocarcinoma↗
Spermatocytic seminoma: an immunohistochemical study.
Spermatocytic seminoma (SS) is an unusual germ cell tumor that behaves in an indolent fashion. Because orchiectomy alone in adequate treatment, it is important to distinguish SS from classic seminoma and other germ cell tumors. Light microscopic distinction usually is possible; however, occasional cases of SS exhibit atypical features, including the presence of a lymphoid infiltrate or microcystic change, which simulate classic seminoma and yolk sac tumor, respectively. Immunohistochemistry might aid in this differential diagnosis, but the immunohistochemical profile of SS is not well reported in the literature. We examined seven SS cases (six men and one non-human primate) with a panel of 14 antibodies directed against placental-like alkaline phosphatase (PLAP), keratins (CAM 5.2, AE1/AE3), vimentin, human chorionic gonadotropin, alpha-fetoprotein, muscle-specific actin, carcinoembryonic antigen, S-100 protein, epithelial membrane antigen, desmin, leukocyte-common antigen, neuron-specific enolase, and human placental lactogen. A previously unreported finding was the presence of focal cytoplasmic staining for low molecular weight cytokeratin (CAM 5.2) in three cases. All other antibodies produced essentially negative results, including anti-PLAP. The PLAP and neuron-specific enolase negativity of SS are in contrast to the positivity of classic seminoma for these markers. A simplified panel of antibodies is recommended to assist in the differentiation of SS from other forms of germ cell neoplasia.
Adult↗
Retroperitoneal xanthogranuloma in a patient with Erdheim-Chester disease.
A case of Erdheim-Chester disease with retroperitoneal and renal sinus xanthogranuloma that occurred in a 50-year-old woman is presented. The 12 previously reported cases of Erdheim-Chester disease associated with retroperitoneal xanthogranuloma are reviewed and compared with 13 sporadic cases of retroperitoneal xanthogranuloma. Retroperitoneal xanthogranuloma is distinguished from inflammatory malignant fibrous histiocytoma by its lack of neutrophils, inconspicuous vascularity, lack of nuclear atypia, and abundant collagen. It is distinguished from inflammatory fibrosarcoma by its numerous foamy histiocytes, relative lack of plasma cells, and lack of nuclear atypia; it is distinguished from retroperitoneal fibrosis principally by its many foamy histiocytes, lack of plasma cells, and lack of vasculitis.
Bone Diseases↗
The correlation of P53 protein expression with proliferative activity and occult metastases in clinical stage I non-seminomatous germ cell tumors of the testis.
Sixty-nine cases of clinical Stage I non-seminomatous germ cell tumors (NSGCT) of the testis were immunostained for the protein product of the p53 tumor suppressor gene using a microwave-based antigen retrieval method. It was assumed that the immunohistochemical detection of the p53 protein corresponded to a point mutation in the p53 gene, the wild-type p53 protein turning over too rapidly to be detected by routine immunohistochemical techniques. The results of p53 staining were then compared with the results, on the same paraffin tissue blocks, of S-phase analysis, as determined by flow cytometry, and the percentage of neoplastic cells exhibiting immunohistochemical positivity for proliferating cell nuclear antigen (PCNA). Thirty-four of 69 (49%) of the clinical Stage I NSGCT exhibited p53-positivity as strong, but focal, intranuclear positivity. Both the mean total S-phase and the mean percentage of PCNA-positive neoplastic cells were significantly higher in the p53-positive cases (27.8% and 89.6%, respectively) compared with the p53-negative cases (17.6% and 66.1%, respectively). Stratification of cases into high (> or = 76%) and low categories for PCNA values correlated significantly (P < 0.0005) with p53-positivity and negativity, respectively, by chi 2 analysis. The positive association of p53 protein expression with higher proliferative indices in NSGCT of the testis is consistent with the observation of p53 mutations correlating with markers of increased tumor aggressiveness in other types of neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)
DNA, Neoplasm↗
Platelet-derived growth factor induces proliferation of hyperplastic human prostatic stromal cells.
Prostatic hyperplasia (BPH) is a very common disease in elderly men and is characterized by abnormal proliferation of the stromal and epithelial cells of the prostate. The observation that BPH often occurs in association with chronic inflammation has led to the examination of the possibility that platelet-derived growth factor (PDGF), which is released in response to inflammation, may be an etiological factor in the genesis of the disease. It has been shown that cultured cells derived from human prostatic tissue express high affinity PDGF-beta receptors based on receptor binding and cross-linking studies with [125I]-PDGF-BB. The experiments presented below demonstrate that PDGF receptors are activated in response to the growth factor and that mitogenesis is induced. PDGF-BB treatment of cultured human prostate cells derived from patients with BPH activates the signal transduction pathway of the PDGF receptor as shown by the presence of several phosphoproteins in antiphosphotyrosine immunoprecipitates, including autophosphorylation of the PDGF receptor. Phosphatidylinositol (PI) 3-kinase activity is also increased in cells stimulated with PDGF. The addition of PDGF-BB to the medium causes of variable but dose-dependent increase in [3H]-thymidine incorporation. This paper describes the first demonstration that PDGF is a potent mitogen for human cells derived from patients exhibiting prostatic hyperplasia, and also demonstrates that the cellular response to PDGF-BB is heterogenous in a manner that is consistent with the varying degree of hyperplasia and inflammation clinically and histologically in the tissue specimens.
Aged↗
Platelet derived growth factor (PDGF), androgens and inflammation: possible etiologic factors in the development of prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is characterized by varying degrees of epithelial and stromal hyperplasia in association with inflammation. Although androgens are known to be important for the growth and function of the prostate, their role in the development of BPH is unclear. The release of platelet-derived growth factor (PDGF) in response to inflammation suggests that PDGF may participate in the development of BPH. Cultured prostate cells derived from patients with BPH were examined for the presence of functional PDGF and androgen receptors. The cells expressed PDGF receptors and responded to PDGF stimulation by the activation of the PDGF signal transduction pathway and a dose-dependent stimulation of cell proliferation. Even though the cells expressed androgen receptors, dihydrotestosterone failed to elicit a mitogenic response. While the role of androgens in BPH remains unclear, these results suggest that inflammation and, specifically, PDGF may be important etiologic factors in the development of BPH.
Aged↗
The roles of fine needle aspiration and needle core biopsies in the diagnosis of primary prostatic cancer.
For more than 50 years, needle core and aspiration biopsy techniques have been used to detect carcinoma of the prostate. Each has had vigorous proponents and many technical innovations have been made to improve the techniques. This report summarizes the developmental history of the techniques, examines their individual merits, reviews studies comparing the methods, and discusses the complications associated with each. Presently, in patients with abnormal rectal examinations, small-gauge transrectal core biopsy and transrectal aspiration biopsy offer similar detection and false-negative rates with very low frequencies of complications.
Biopsy, Needle↗
Inhibition by tiazofurin of inosine 5'-phosphate dehydrogenase (IMP DH) activity in extracts of ovarian carcinomas.
Cancer cells have an increased ability to synthesize GTP (guanosine triphosphate) because of increased activity of IMP DH (inosine 5'-phosphate dehydrogenase, EC 1.1.1.205). Because IMP DH activity is rate limiting for de novo biosynthesis of GTP, this enzyme was suggested as a sensitive target for chemotherapy. Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) is converted in the cells into the active metabolite, TAD, (thiazole-4-carboxamide adenine dinucleotide) which potently inhibits IMP DH activity. By adding TAD to tissue extracts one can determine the extent of inhibition of IMP DH. We applied the IMP DH assay method to extracts of normal ovaries (N = 11) and epithelial ovarian carcinomas (N = 10). The IMP DH activity (mean +/- SE) in ovarian carcinoma was 21.1 +/- 5.8 which was markedly higher than that observed in normal ovaries (2.9 +/- 0.7 nmol/hr/mg protein) (P < 0.05%). The inhibition by TAD of IMP DH activity in ovarian carcinomas (N = 4) was 81%. The results indicate that IMP DH activity is elevated sevenfold in ovarian carcinomas as compared to normal ovary and can be inhibited by exposure to tiazofurin (TAD). Similar high IMP DH activity and inhibition of the activity by TAD was observed in patients with chronic granulocytic leukemia in blast crisis among whom 70 to 80% remissions were reported. Since there is increased IMP DH activity in human ovarian carcinomas and in OVCAR-5 cells and tiazofurin and TAD inhibit IMP DH activity of these cells and the proliferation of human ovarian carcinoma xenografts in the mouse, tiazofurin may merit serious consideration for a Phase II trial for patients with recurrent/refractory epithelial ovarian carcinoma.
Adenocarcinoma↗
Unusual forms of carcinoma of the urinary bladder.
Carcinomas of the urinary bladder, which differ histologically from the usual transitional cell carcinoma of the bladder, are reviewed. These tumors, which account for approximately 15% of all bladder carcinomas, have diverse microscopic appearances. They fall into four major categories: variant forms of urothelial (transitional cell) carcinoma, squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. In the first category, the most common are carcinomas with glandular or squamous differentiation. Less common, but more troublesome diagnostically, are variants in which the cells are spindle shaped (sarcomatoid carcinoma), form small cysts (microcystic carcinoma), or differentiate toward trophoblast. In other variants, the stroma has unusual features that may lead to diagnostic difficulty. These are carcinomas with pseudosarcomatous stroma, osseous or cartilaginous metaplasia, or osteoclast-type giant cells. Also reviewed are squamous cell carcinoma and its variant, verrucous carcinoma. Vesical adenocarcinoma has several variants, including signet-ring cell and clear cell types. Finally, the category of undifferentiated carcinoma, including small cell carcinoma, giant cell carcinoma, and lymphoepithelioma-like carcinoma, is discussed.
Adenocarcinoma↗
Regulation of de novo and salvage pathways in chemotherapy.
An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT-29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment.
Antimetabolites, Antineoplastic↗
Stromal osseous metaplasia in carcinoma of the bladder.
Osseous metaplasia of the stroma of carcinomas of the bladder is a rare finding that must be distinguished from osteosarcoma and carcinosarcoma. We report a case of multifocal osseous metaplasia in a high grade urothelial carcinoma with extensive glandular differentiation, arising in the base of the bladder of an 84-year-old man. Reports of 11 other cases of stromal osseous metaplasia in primary bladder carcinomas and of 5 cases of stromal osseous metaplasia in metastases of bladder carcinoma are reviewed.
Aged↗