Biomedical subjects

J N Eble

Publications and source records attributed to J N Eble.

At least 73 records · Page 4Linked to original sources

PubMed1991

Tiazofurin down-regulates expression of c-Ki-ras oncogene in a leukemic patient.

The increased activity in cancer cells of inosine 5'-monophosphate dehydrogenase (IMP DH, EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, was suggested as a sensitive target for chemotherapy. Tiazofurin (NSC 286193), through its conversion to the active metabolite, thiazole-4-carboxamide adenine dinucleotide (TAD), is a strong inhibitor of IMP DH. In our clinical trial, tiazofurin caused return to the chronic phase in patients with chronic granulocytic leukemia in blast crisis (Tricot, G.; Jayaram, H.N.; Weber, G.; Hoffman, R. Tiazofurin: Biological effects and clinical uses. Int. J. Cell Cloning 8:161-170; 1990). In K562 human leukemic cells, tiazofurin down-regulated the expression of c-Ki-ras and c-myc oncogenes, which was followed by induced differentiation. We now report down-regulation by tiazofurin of the c-Ki-ras oncogene in a patient with chronic granulocytic leukemia in blast crisis. A single tiazofurin infusion (2,200 mg/m2) on days one and two decreased IMP dehydrogenase activity (the apparent t1/2 was 30 min), GTP concentration (the apparent t1/2 was 6 hr), and expression of ras (the apparent t1/2 was 8 hr) and c-myc (the apparent t1/2 was 38.5 hr) oncogenes in the leukemic cells. No further tiazofurin was given, because on days three and four the chemotherapeutic impact became evident in a tumor-lysis syndrome and the blast cells were cleared from the periphery by day five. The decrease in IMP DH activity, GTP concentration, and expression of c-Ki-ras oncogene were early markers of the successful chemotherapeutic impact of tiazofurin in a patient with chronic granulocytic leukemia in blast crisis.

Adenine Nucleotides↗

PubMed1991

Prostatic stromal hyperplasia with bizarre nuclei.

Prostatic stromal hyperplasia with bizarre nuclei is an uncommon variant of nodular hyperplasia that may be confused with mesenchymal malignancy but that can usually be distinguished by the degenerative character of the nuclear changes, absent to negligible mitotic rate, and relatively sparse cellularity. We report a case in a 73-year-old man and review six other cases, which, to our knowledge, are the only ones that have been reported previously.

Aged↗

PubMed1990

Post-surgical necrobiotic granulomas of urinary bladder.

Palisading necrobiotic granulomas of the prostate are an uncommon but well-recognized sequela of transurethral surgery. Similar granulomas occurring in 3 patients after transurethral surgery of the urinary bladder are reported. In each case, the lesions were discovered as a result of biopsies done subsequent to transurethral resections of bladder tumors. An idiosyncratic hypersensitivity reaction to a diathermically induced change in the antigenicity of the subepithelial connective tissue is suggested as the cause of these granulomas.

Aged↗

PubMed1989

Spermatozoa-containing simple cysts of the rete testis.

Simple cysts of the testis are rare benign lesions of uncertain etiology. We report 2 spermatozoa-containing cysts of the rete testis found incidentally in the left testicle of a 56-year-old man evaluated by ultrasound for hydrocele. The presence of spermatozoa in the cyst fluid has not been observed previously and confirms the connection of the cysts with the seminiferous tubular system.

Cysts↗

PubMed1989

Monoclonal antibody L/1C2 reactive with a human carcinoma associated antigen.

A murine IgG3 monoclonal antibody which defines a human carcinoma associated antigen is described. The antibody, designated L/1C2, was made against a human lung squamous cell carcinoma line designated USCLS-1. It reacts with the surface of 15 of 16 viable human carcinoma cell lines and was detected in 70 of 78 frozen sections of human carcinomas. Melanoma cell lines and frozen sections of melanomas and a lymphoma were unreactive. Normal tissue reactivity included vessels, plus some ducts, glandular structures, and epithelial surfaces. Similar normal tissue reactivity patterns were seen with Rhesus monkey tissue samples. Immunoprecipitation studies indicate that L/1C2 reacts with a glycoprotein doublet which migrates in the range of 110,000 to 140,000 Mr under reducing conditions. Fluorescence analysis suggests this antigen is internalized following reaction with the L/1C2 antibody. Using in vitro human tumor cell growth inhibition assays, it was possible to achieve significant growth inhibition with L/1C2, while another target cell-reactive antibody in the same assay had no inhibitory effect.

Adenocarcinoma↗

PubMed1989

Endoluminal radio-frequency electrocautery for permanent ureteral occlusion in swine.

An animal experiment was undertaken to assess the feasibility of using radio-frequency current-mediated thermal injury of the ureter to produce ureteral occlusion by means of an endoluminal approach. Through open pyelotomies, balloon angioplasty catheters coated with gold bipolar electrodes were introduced into the ureters. Doses (at 650 kHz) were delivered for specific energy totals in 13 of 15 ureters in eight pigs. Two ureters served as controls (balloon inflation without current application). In six experimental animals not killed immediately after the procedure, postoperative ureteral manometric studies and nephrostography were performed and nephrostomy drainage was maintained until death (1-8 weeks). Treatment with 200-400 J produced safe, reliable occlusion by 4 weeks. At histopathologic study at 4 and 8 weeks, necrotic muscularis propria had been replaced by fibrous tissue. Cardiac rhythm was not affected during treatment.

Angioplasty, Balloon↗

PubMed1989

Benign and low-grade papillary lesions of the urinary bladder: a review of the papilloma-papillary carcinoma controversy, and a report of five typical papillomas.

The controversial topic concerning the most appropriate nomenclature for low-grade papillary lesions of the urinary bladder is reviewed on the basis of the literature and the authors' experiences. This undertaking was prompted by a recent report in which use of the designation "papilloma" was advocated for lesions that generally had been diagnosed as grade 1 papillary urothelial carcinoma. The literature indicates that 10% to 20% of patients with a noninvasive low-grade papillary tumor of the bladder will later have invasive bladder cancer. This significant outcome in a minority of such patients warrants very careful follow-up for the group as a whole, irrespective of the terminology used. The authors contrast the features of papillary urothelial carcinoma with a series of five cases, which they interpret as true papillomas. They believe that these low-grade papillary lesions can be distinguished from true papillomas and do not favor a change in terminology. Some of the problems in the evaluation of inverted papilloma and inverting urothelial carcinoma are briefly reviewed as are other selected papillary lesions of the urinary bladder.

Adult↗

PubMed1988

Relation of proliferative activity to survival in patients with advanced germ cell cancer.

Patients with advanced disseminated germ cell tumors of the testis, retroperitoneum, and mediastinum have impaired survival compared to other patients with disseminated germ cell tumors having less bulky metastatic disease. Among patients with advanced disseminated germ cell tumors, we currently lack adequate predictors of long-term survival. Flow cytometric analysis of the paraffin-embedded, formalin-fixed tumor blocks of 50 of these patients suggests that proliferative activity is significantly correlated with survival (p less than 0.001) in multivariate analysis. Log (beta-human chorionic gonadotropin) is the only other useful predictor of long-term survival in multivariate analysis of prognostic factors in this group of patients. Flow cytometric DNA analysis may be useful in predicting survival in patients with advanced disseminated germ cell tumors.

Cell Cycle↗

PubMed1988

In vivo antitumor activity demonstrated with squamous carcinoma reactive monoclonal antibody-Vinca immunoconjugates.

An immunoconjugate (PF1/D-DAVLBHYD), made with the squamous carcinoma reactive monoclonal antibody PF1/D and a derivative of vinblastine, DAVLBHYD, was shown to suppress established T222 human tumor nude mouse xenografts using a multidose protocol. Treatments of xenograft-bearing mice with free drug, free antibody, or a mixture of the two, were unsuccessful at achieving suppression without associated toxicity, using otherwise identical protocols. A Vinca conjugate with a related squamous carcinoma reactive monoclonal antibody, PF1/B, was shown to have similar tumor suppressive activity. In a dual immunoconjugate therapy protocol, PF1/D-DAVLBHYD and PF1/B-DAVLBHYD had additive antitumor effects which were consistent with their complementary tumor reactivity.

Animals↗

PubMed1988

Simple cyst of the rete testis.

We report a case of a simple cyst in the upper pole and connected to the mediastinum testis at the rete testis. The cyst appeared to arise from a dilated rete duct, and it was spherical, smooth-walled and filled with clear fluid. The epithelium was lined with a single layer of cuboidal or flattened cells, with no evidence of squamous differentiation.

Aged↗

PubMed1988

Enzymic imbalance in serine metabolism in human colon carcinoma and rat sarcoma.

The activities of 3-phosphoglycerate dehydrogenase, an enzyme of serine biosynthesis, and serine hydroxymethyltransferase, serine dehydratase and serine aminotransferase, which are competing enzymes of serine utilization, were assayed in human colon carcinomas from patients and in transplantable rat sarcomas. Serine dehydratase and serine aminotransferase activities were absent, whereas 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase activities were markedly increased in both tumour types. Serine hydroxymethyltransferase catalyses the formation of glycine and methylene tetrahydrofolate which are important precursors for nucleotide biosynthesis. The observed enzymic imbalance in these tumours ensures that an increased capacity for the synthesis of serine is coupled to its utilisation for nucleotide biosynthesis as a part of the biochemical commitment to cellular replication in cancer cells. That this pattern is found in sarcomas and carcinomas, and in tumours of human and rodent origin, signifies its universal importance for the biochemistry of the cancer cell and singles it out as a potential target site for anti-cancer chemotherapy.

Aged↗

PubMed1988

Increased thymidylate synthase (EC 2.1.1.45) activity in normal and neoplastic proliferation.

Thymidylate (dTMP) synthase (EC 2.1.1.45) activity was measured in 100,000 x g supernatant fluid with a sensitive, rapid radio assay. The activity in normal rat liver was low (0.098-0.204 nmol/hr/mg protein). dTMP synthase specific activities in rat thymus, spleen, bone marrow, testis, lung, heart, brain, kidney, and small intestine were 6297, 1842, 1500, 788, 215, 76, 61, 39 and 24%, respectively, of that of the liver. The activity in 5-day-old rat liver was 16-fold higher than in adult. dTMP synthase activity increased in rat hepatomas to 7- to 125-fold of that of normal rat liver. There was a significant correlation between the increase in synthase activity and the proliferation rates of the hepatomas. In 8 human colon carcinomas, dTMP synthase activity increased to 2.9- to 8-fold of that of normal human colon mucosa. In leukemic leukocytes from 3 leukemia patients, activity was 8- to 10-fold higher than in normal leukocytes.

Aging↗

PubMed1988

Glycoconjugate expression in human renal oncocytomas. A lectin histochemical study.

A panel of lectins chosen for its specificity for segments of the nephron was used in an avidin-biotin-peroxidase reaction to stain 13 human renal oncocytomas and a specimen of oncocytomatosis. The lectins were derived from Lotus tetragonolobus, Glycine max, Dolichos biflorus, and Arachis hypogaea. Two patterns predominated: one of staining with the lectins of D biflorus and G max, suggesting distal tubular or collecting-duct differentiation, and one of staining with the lectin of L tetragonolobus, suggesting proximal tubular differentiation.

Adenoma↗

PubMed1987

Flow cytometry derived DNA content of the primary lesions of advanced germ cell tumours.

We currently lack good prognostic indicators for patients with advanced disseminated germ cell tumours (GCT). An analysis of archival tumour samples of forty-nine patients with advanced GCT for flow cytometry derived DNA content suggests an inverse relationship between tumour proliferative activity and patient survival. The great majority of patients with advanced GCT have aneuploid tumour subpopulations. This analysis suggests that the survival of patients with advanced GCT may depend in part on kinetic variables present in the primary tumour.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

Glycogen-rich clear cell carcinoma of the urethra: an ultrastructural study.

A 49-year-old black woman developed a urethral glycogen-rich clear cell carcinoma. She was treated with anterior pelvic exenteration. The resected lymph nodes, vagina, uterine cervix, endometrium, ovaries, and urinary bladder were free of neoplasm. Histologically the neoplasm consisted of clear cells growing in sheets and occasional papillary structures. In some areas, hobnail cells were present. Ultrastructurally, the cells had apical caps, short microvilli, and complex cell bases, and contained abundant glycogen. These features were identified in one, but not the other of two previously reported cases. Because glycogen-rich clear cell carcinomas of the lower urinary tract do not resemble ultrastructurally mesonephric remnants or carcinomas known to arise from them, these glycogen-rich clear cell carcinomas should not be called "mesonephromas" as has been the practice.

Adenocarcinoma↗

PubMed1986

Cellular deoxyribonucleic acid content of renal oncocytomas: flow cytometric analysis of paraffin-embedded tissues from eight tumors.

Formalin-fixed, paraffin-embedded tissues from eight renal oncocytomas were analyzed using a Coulter Epics V cell sorter. Samples were processed using Hedley's method modified by including centrifugation through sucrose, RNAse digestion, and propidium iodide staining. The nuclei were excited using 200 mw of laser power at 488 nm. The tissues were all from surgical specimens acquired between 1972 and 1983, and the neoplasms met stringent light and electron microscopic criteria for the diagnosis. Sixteen samples were analyzed from the eight tumors; the coefficients of variation on the interpretable G1 peaks ranged from 3.95 per cent to 7.62 per cent with a mean of 5.46 per cent. One of the tumors had been frozen and yielded uninterpretably wide peaks. Control samples of non-neoplastic kidney from six of the specimens had coefficients of variation in a similar range. All of the oncocytomas with acceptable histograms had single, sharp G1 peaks with no evidence of aneuploidy. Proliferative indices were calculated and ranged from 0.02 to 0.18 for the oncocytomas and from 0.01 to 0.03 for renal cortex. The mean of the ratios of proliferative indices between the oncocytomas and the corresponding renal cortical samples was 4.5. These data support the concept that renal oncocytomas are euploid neoplasms with significant growth rates and are consistent with their benign biologic behavior and propensity to grow locally to large size.

Adenoma↗

PubMed1986

Villous adenoma of the urachus with mucusuria: a light and electron microscopic study.

After 2 years of mucusuria a villous adenoma of the urachus was resected from a woman by partial cystectomy and excision of the entire urachus. Convalescence was uneventful and the patient was well 12 months later. Urachal adenomas are rare, this being the sixteenth case reported. Generally, they are multilocular cystic tumors lined by columnar epithelium with a population of mucous goblet cells. Often, there is a striking resemblance to gut epithelium. Ultrastructurally, by transmission and scanning electron microscopy, the tissue resembles gut mucosa. Urinary mucus is a common and relatively specific symptom for adenomas of the lower urachus, occurring in 7 of 11 cases. Resection alone is effective therapy but care must be exercised to avoid spilling adenoma cells in the peritoneum.

Adenoma↗

PubMed1986

Etiology of pure tricuspid regurgitation based on anular circumference and leaflet area: analysis of 45 necropsy patients with clinical and morphologic evidence of pure tricuspid regurgitation.

Despite recent renewed interest in the detection of tricuspid valve regurgitation by echocardiographic and Doppler techniques, little morphologic information is available on dysfunctioning tricuspid valves. This report describes 45 necropsy patients with clinical and morphologic evidence of pure (no element of stenosis) tricuspid regurgitation and provides morphometric observations (anular circumference, leaflet area) of the tricuspid valve useful in determining the etiology of pure tricuspid regurgitation. Of 45 patients, 24 (53%) had pure tricuspid regurgitation resulting from an anatomically abnormal valve (prolapse in 7, papillary muscle dysfunction in 6, rheumatic disease in 5, Ebstein's anomaly in 3, infective endocarditis in 2, carcinoid tumor in 1), and 21 (47%) had an anatomically normal valve with systolic pulmonary artery hypertension (cor pulmonale in 12, mitral stenosis in 9). Anular circumference was dilated (greater than 12 cm) in patients with various causes of pulmonary hypertension, floppy valve and Ebstein's tricuspid anomaly. Leaflet area was increased in floppy valve and Ebstein's anomaly. Of the 45 patients, 24 had pulmonary systolic artery pressure measurements available for correlation with tricuspid valve morphology. Pulmonary artery pressures accurately predicted morphologically normal from abnormal valves in 16 patients (89%). Morphologic overlap occurred in six patients with pulmonary pressures of 41 to 54 mm Hg. Of these six, the additional knowledge of normal or dilated anular circumference correctly separated valves with normal and abnormal leaflets.

Adolescent↗