Adhesion protein studies provide new clue to metastasis.
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Biomedical subjects
Publications and source records attributed to P Kahn.
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A total of 92 patients underwent continent urinary diversion with an extended, detubularized right colonic segment as the urinary reservoir and the distal ileum as a continent catheterizable efferent system. In this series 65 patients were followed for 6 to 46 months (average 17 months). Our reservoir allows the accommodation of a large volume of urine; urodynamic studies in 28 patients demonstrated a maximum reservoir capacity varying between 550 and 1,200 cc (average 747 cc). Maximal reservoir pressures ranged from 10 to 58 cm. water (average 35 cm. water). Of the 127 ureterocolonic reimplantations 4 ureters were initially reimplanted with a modified Le Duc procedure, 26 ureters were managed subsequently with the Goodwin transcolonic approach and 91 reimplantations were done with a direct (nontunneled) mucosa-to-mucosa anastomosis. The overall success rates with each of the 3 techniques (absence of reflux and obstruction) were 75, 88.6 and 90.1%, respectively. Six megaureters underwent imbrication and direct reimplantation, and 3 of these (50%) became obstructed. Two converted ileal conduits were opened at the antimesenteric edge and were patched to the reservoir while the ureteroileal anastomosis was left undisturbed. One patient (1.5%) died of pulmonary embolism. Medical and surgical complications occurred only in the group who underwent simultaneous cystectomy and the over-all rate of complication was comparable to previous series with ileal conduits. The double row plication of the distal ileum and ileocecal valve allows for easy catheterization every 4 to 6 hours and 63 patients (97%) remain continent between catheterization. Four patients (6%) required reoperation for correction of incontinence or other complications. Our satisfactory experience with these patients makes this technique an excellent approach to achieving continent urinary diversion.
Large bowel obstruction constitutes an emergency abdominal condition and necessitates prompt surgical treatment. The optimal approach is still controversial as to whether to perform a diverting colostomy only or a tumor resection with or without primary anastomosis. Seventy-one elderly and high-risk patients were treated by proximal diverting colostomy through a right upper abdominal incision. The operative mortality was 8.5%, with an additional morbidity of 20.5%. Stomal complications appeared in 6.1% of the survivors. Seventy-five percent of surviving patients underwent successful resection and closure of colostomy within 3 months without additional mortality. Others were not operated because of metastatic disease or severe concomitant disease. We conclude that although primary resection should be attempted in good risk patients, for those patients who are elderly and at high risk, a simple life-saving procedure, such as fecal diversion, could alleviate obstructions with relatively low morbidity and mortality and improve the patient's prospects for subsequent definitive surgery.
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Previous work has established that the v-erbA oncogene inhibits the temperature-induced differentiation of chick erythroblasts transformed with temperature-sensitive oncogene mutants. Here we demonstrate that v-erbA in differentiating erythroblasts specifically arrests expression of the erythrocyte anion transporter (band 3) gene at the transcriptional level. The v-erbA-induced differentiation block can be overcome by inducing cells to differentiate at alkaline pH. Under these conditions, which possibly impair biological activity of v-erbA, the maturing cells now express the anion transporter gene at high levels. However, its transcription is specifically and rapidly suppressed if v-erbA activity is restored by culturing the cells at neutral pH. Similar but less pronounced inhibition of gene expression by v-erbA was observed for the delta-amino-levulinic acid synthase gene. Additional evidence obtained with an inhibitor of band 3 activity suggests that the v-erbA-induced inhibition of band 3 gene expression is at least partly responsible for the differentiation block caused by this oncogene.
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Neutral endopeptidase (EC 3.4.24.11) is a major constituent of kidney brush border membranes. It is also present in the brain where it has been shown to be involved in the inactivation of opioid peptides, methionine- and leucine-enkephalins. For this reason this enzyme is often called 'enkephalinase'. In order to characterize the primary structure of the enzyme, oligonucleotide probes were designed from partial amino acid sequences and used to isolate clones from kidney cDNA libraries. Sequencing of the cDNA inserts revealed the complete primary structure of the enzyme. Neutral endopeptidase consists of 750 amino acids. It contains a short N-terminal cytoplasmic domain (27 amino acids), a single membrane-spanning segment (23 amino acids) and an extracellular domain that comprises most of the protein mass. The comparison of the primary structure of neutral endopeptidase with that of thermolysin, a bacterial Zn-metallopeptidase, indicates that most of the amino acid residues involved in Zn coordination and catalytic activity in thermolysin are found within highly honmologous sequences in neutral endopeptidase.
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The v-erbB, v-src, v-fps, v-sea, and v-Ha-ras oncogenes induce avian erythroid progenitor cells to self-renew in an erythropoietin-independent manner. These transformed erythroblasts retain both their capacity to differentiate into erythrocytes and their requirement for complex growth media. However, previous studies showed that erythroblasts transformed by v-erbB plus v-erbA (which by itself is not oncogenic) are blocked in differentiation and grow in standard media. Here we show that the introduction of v-erbA into erythroblasts transformed with v-src, v-fps, v-sea, or v-Ha-ras likewise induces a fully transformed phenotype. It also reduces the capacity of ts sea- and ts erbB-transformed erythroblasts to differentiate terminally in an erythropoietin-dependent manner after a temperature shift. Cooperativity involving v-erbA also occurs in vivo since chicks infected with a retroviral construct encoding v-erbA and v-src develop both acute erythroblastosis and sarcomas.
The v-erb B oncogene, as well as other oncogenes of the src-gene family transform immature erythroid cells from chick bone marrow in vivo and in vitro. The erb B-transformed erythroid cells differ from normal late erythroid precursors (CFU-E) in that they have acquired the capacity to undergo self-renewal as well as to differentiate terminally. They also do not require the normal erythroid differentiation hormone, erythropoietin, for either process. Cooperation of v-erb B with a second oncogene, v-erb A, results in a differentiation arrest of the transformed cells, which now only use the self-renewal pathway. Studies with conditional and non-conditional mutants in both v-erb B and v-erb A will be presented to elucidate further how the transforming proteins encoded by these oncogenes, gp74erb B and gp75gag-erb A, affect the differentiation programme of the infected erythroid precursor with the outcome of hormone-independent leukaemic cells arrested at an early stage of erythroid differentiation.
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Fibronectin (FN; also called large external transformation-sensitive [LETS] protein or cell-surface protein [CSP]) is a large cell-surface glycoprotein that is frequently observed to be either absent or greatly reduced on the surfaces of malignant cells grown in vitro. Because FN may be a useful molecular marker of cellular malignancy, we have carried out an extensive screening to test the specific association among the degree of expression of FN, anchorage-independent growth, and tumorigenicity in the athymic nude mouse. A variety of diploid cell strains and established cell lines were tested for the expression of surface FN by indirect immunofluorescence using rabbit antisera against human cold insoluble globulin, rodent plasma FN, or chicken cell-surface FN. Concomitantly, the cells were assayed for tumor formation in nude mice and for the ability to form colonies in methylcellulose. Tumorigenic cells often showed very low surface fluorescence, confirming earlier reports. However, many highly tumorigenic fibroblast lines from several species stained strongly with all three antisera. In contrast, the anchorage-independent phenotype was nearly always associated with tumorigenicity in approximately 35 cell lines examined in this study. In another series of experiments, FN-positive but anchorage-independent cells were grown as tumors in nude mice and then reintroduced into culture. In five of the six tumor-derived cell lines, cell-surface FN was not significantly reduced; one such cell line showed very little surface FN. Our data thus indicate that the loss of cell-surface FN is not a necessary step in the process of malignant transformation and that the growth of FN-positive cells as tumors does not require a prior selection in vivo for FN-negative subpopulations.
Follow-up scintigraphies with 99m Tc pyrophosphate 3--4 weeks and 6--12 months after a myocardial infarction revealed the possibility of persisting a myocardial tracer activity in cases in which reinfarction can be excluded. There was a relation between the persistence of the tracer activity and the pressure in the pulmonary artery under stress conditions. The diastolic pulmonary pressure was regular in those patients whose scintiphotos showed no tracer activity in the myocardial area in the follow-up scintigraphy. Patients who showed a persisting tracer activity in the infarcted areal had elevated pressures in the pulmonary artery under stress conditions or even at rest. The elevation of the diastolic pulmonary pressure is a sign of an elevated enddiastolic pressure in the left ventricle caused by a limited left ventricular function. This could be proved by left ventriculography. The results in follow-up scintigraphy 3--4 weeks and 6--12 months after the infarction were quite similar. Therefore we believe that the results of a follow-up scintigraphy 3--4 weeks after an infarction allows to draw prognostic inferences about the further course of the disease.
In Austria primary carcinoma of the liver (plc) is no rare malignancy. From 1973 and 1979, in our department, 188 patients with plc had been registered. By separate evaluation of the results of alpha-1-fetoprotein (AFP)-determination and 67-gallium-liverscintigraphy, a diagnostic accuracy of 81.6%, resp. 78. % could be demonstrated. By combination of both methods, a correct diagnosis of plc was obtained in 95%. Based on the promising results of lobectomies performed in patients with plc, therapeutic nihilism is not longer justifiable.
A distinction can be made between invasive and non-invasive methods in myocardial scintigraphy. Myocardial perfusion scintigraphy as an invasive procedure always requires catherization of the coronary arteries and can be performed only in conjunction with coronary arteririography. The technique of this type of myocardial scintigraphy is described in detail and an explanation given of the normal scintigram and the results obtainable by this method in cases of coronary heart disease. In particular, the possibilities of "doulbe-radionuclide" scintigraphy are discussed. The non-invasive methods serve either to image the still-viable myocardium (cold-spot technique) or for direct visualization of recently-infarcted myocardial tissue (hot-spot technique). The diagnostic importance of these procedures is stressed, especially dual radionuclide investigation of recent myocardial infarct with technetium and thallium.