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Biomedical subjects

J N Eble

Publications and source records attributed to J N Eble.

At least 91 records · Page 5Linked to original sources

Inactivation by acivicin of carbamoyl-phosphate synthetase II of human colon carcinoma.

The effect of the anti-tumor, anti-glutamine drug acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, was determined on the activity of the rate-limiting enzyme of de novo pyrimidine biosynthesis, carbamoyl-phosphate synthetase II (glutamine-hydrolyzing) (EC 6.3.5.5), in human colon carcinoma. The synthetase II activity in human colon carcinoma was elevated 2- to 3-fold over values of the normal colon mucosa, and the substrate kinetic constants were similar for the enzyme in normal and neoplastic colon. The Km for glutamine was 17 microM (colon carcinoma) and 23 microM (normal mucosa), whereas the Km for ATP was 2.1 and 1.7 mM in tumor and mucosa respectively. The synthetase II activity in colon carcinoma was inhibited to a similar extent by UMP, UDP and UTP (36-41%). The three uracil nucleotides were also equally effective in inhibiting the enzyme from normal mucosa (39-46%). Both enzymes were activated by PRPP (63 and 57%) in mucosa and carcinoma respectively. Acivicin in vitro selectively inactivated the glutamine-dependent synthetase II from human colon carcinoma, and it did not affect the ammonia-dependent activity. The acivicin inactivation constant (Kinact) was 100 microM, and the minimum inactivation half-time (T) was 0.7 min. Acivicin most likely exerts its effect against human colon synthetase II by acting as an active site directed affinity analogue of L-glutamine.

Antibiotics, Antineoplastic↗

A, B and H antigens in normal urothelium: an immunohistochemical study using monoclonal antibodies with the avidin-biotin complex technique.

Immunohistochemical staining for the A, B and H blood group antigens was studied in 61 normal human ureters using monoclonal antibodies with avidin-biotin complex application. Thirty-seven of these were archival material, and 24 were processed prospectively. In 100 per cent of the prospectively processed ureters, A, B and H antigens were demonstrated corresponding to the blood type of the source. Archival material stained for A, B and H 65 per cent, 50 per cent and 100 per cent of the time, respectively. Serial sampling of prospectively processed ureters showed diminution of staining with prolongation of immersion in formalin. A characteristic staining pattern was found in ureters from patients with type B blood.

ABO Blood-Group System↗

Laryngeal blastoma. A light and electron microscopic study of a novel entity analogous to pulmonary blastoma.

A neoplasm morphologically analogous to pulmonary blastoma, but arising in the pyriform fossa of the larynx, is described and illustrated. The patient, a 65-year-old white man, was treated with laryngectomy and is alive and free of disease 13 months later. Grossly polypoid on a broad stalk, the neoplasm consisted of a mixture of blastematous, mesenchymal, and epithelial elements. Ultrastructural examination showed that the spindle and stellate cells were truly mesenchymal. The name "laryngeal blastoma" is proposed for this novel entity.

Aged↗

Purine enzymology of human colon carcinomas.

The purpose of this study was to elucidate the purine enzymic programs of human primary colorectal carcinomas. Marked alteration in the enzymology of the human colon neoplasm clearly distinguished it from that of the normal colon mucosa. In the human colon mucosa, the activities of ribonucleotide reductase, inosine phosphate dehydrogenase, formylglycinamidine ribonucleotide synthetase, guanosine phosphate synthetase, and amidophosphoribosyltransferase were 0.042, 5.2, 5.6, 8.2 and 36.0 nmol/h/mg protein, respectively, and in the colon carcinomas the activities increased to 755, 575, 295, 280, and 294% of the normal values. The activities of the salvage enzymes, adenine and hypoxanthine-guanine phosphoribosyltransferases, were 310, 249, and 602 nmol/h/mg protein, respectively, whereas in the tumors, only the activity of adenine phosphoribosyltransferase was increased (2-fold). The markedly higher absolute enzymic capacity for salvage in the tumors accounts, in part at least, for the lack of chemotherapeutic success of inhibitors of enzymes of de novo synthesis that have been used in the clinical treatment of colorectal carcinomas. Combinations of inhibitors of de novo biosynthesis and blockers of the salvage enzymes or of salvage transport (e.g., dipyridamole) should improve the chemotherapy of colon neoplasms. Since in the colon carcinoma the activities of glutamine-utilizing enzymes (guanosine phosphate and formylglycinamidine ribonucleotide synthetase and amidophosphoribosyltransferase) were markedly increased, and the glutamine concentration was decreased (50%), treatment with an antiglutamine agent (e.g., acivicin) should be of relevance. Since the activity of ribonucleotide reductase, the rate-limiting enzyme of nucleic acid biosynthesis, was markedly increased in the colon neoplasms, combination chemotherapy might include drugs against this enzyme.

Colon↗

Malignant sex cord-stromal tumor of testis.

We report a case of sex cord-stromal tumor in the testis, which metastasized to the retroperitoneal space, resulting in death 13 months after orchiectomy. The primary lesion consisted of granulosa cells, theca cells, Sertoli cells and undifferentiated gonadal stroma. Biopsy of the retroperitoneal metastasis showed predominance of the Sertoli cell component.

Adult↗

Morphologic features of renal oncocytoma: a light and electron microscopic study.

Five renal oncocytomas were studied by light and electron microscopy. Five glutaraldehyde-fixed blocks from each tumor were examined. Scarce short, blunt microvilli, plasmalemmal interdigitations, basement membrane protuberances, and round or oval mitochondrial profiles were found, suggesting that these neoplasms arise from the epithelium of the distal tubule. Morphologic criteria for the diagnosis of renal oncocytoma, including ultrastructural demonstration of cytoplasmic filling by mitochondria, are presented.

Adenoma↗

Extrapulmonary oat-cell carcinoma of the tongue: an electron-microscopic study.

An extrapulmonary oat-cell carcinoma arose in the tongue of a 62-year-old man who had a long history of cigarette smoking and ethanol ingestion. At presentation, he had the primary tongue lesion and cervical lymph-node metastases only, and search for a pulmonary primary was negative. Ten months later he died with metastases to liver, cerebrum, ribs, vertebrae, calvarium, and clavicle. Electron microscopy demonstrated cells with cytoplasmic processes and many dense-core neurosecretory granules that had a tendency to concentrate in the processes. Cells were linked by desmosomes. Electron microscopy is necessary for definitive diagnosis of extrapulmonary oat-cell carcinomas.

Carcinoma, Small Cell↗

Fetal rhabdomyomatous nephroblastoma.

A case of fetal rhabdomyomatous nephroblastoma is reported. The neoplasm distended the renal pelvis, resembling a sarcoma botryoides. The patient died postoperatively of pneumonia and an autopsy showed no residual neoplasm.

Child, Preschool↗

Transitional cell carcinoma of the fossa navicularis of the male urethra.

We report a case of transitional cell carcinoma arising in the fossa navicularis, a portion of the male urethra ordinarily lined by squamous epithelium. This is the third reported case of transitional cell carcinoma of the distal urethra. The neoplasm metastasized to superficial inguinal lymph nodes.

Carcinoma, Transitional Cell↗

Cerebral histoplasmoma. Case report.

A 55-year-old man presented with dementia and seizures of recent onset. A computerized tomography scan revealed a ring-like lesion in the left occipital lobe, which on resection was found to be a histoplasmoma. Cerebral histoplasmoma is rare and simulates a metastatic brain tumor. Only eight cases of this entity have been reported.

Brain Diseases↗

Ultrastructure of Buschke-Loewenstein tumor.

A 44-year-old man suffered a Buschke-Loewenstein tumor that was treated by distal penectomy. Ultrastructurally, this tumor showed widened intercellular spaces, prominent microvilli, decreased numbers of and incompletely developed desmosomes, decreased tonofilaments, cytoplasmic dense bodies, enlarged nucleoli and annular nuclear bodies. These ultrastructural features are quite similar to those of squamous carcinoma but are dissimilar to those of condyloma acuminatum and, to a lesser extent, verrucous carcinoma. These data suggest that electron microscopy may be useful in differentiating the neoplastic Buschke-Loewenstein tumor from large condyloma acuminatum.

Adult↗