Half-day release for FMP: a curriculum.
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Curriculum↗
Biomedical subjects
C L Jackson
Publications and source records attributed to C L Jackson.
Transforming growth factor-alpha acts as an autocrine growth factor in ovarian carcinoma cell lines.
The potential of transforming growth factor-alpha (TGF-alpha) to function as an autocrine growth factor was evaluated in numerous ovarian carcinoma cell lines. All 17 lines which were examined expressed the epidermal growth factor receptor and 16 cell lines, in addition, concomitantly secreted TGF-alpha. Radioimmunoassay of processed serum-free-conditioned medium indicated TGF-alpha concentrations ranging from 16 to 197 pg/ml, or 1.5 to 95 ng/10(8) cells. 125I-TGF-alpha bound to a single class of high-affinity-binding sites on the surface of the cells. The dissociation constant for the 125I-TGF-alpha/epidermal growth factor receptor complex ranged from 0.21 to 5.3 nM with receptor numbers from 3,500 to 96,000/cell, depending upon the cell line. The growth of 8 ovarian cell lines was stimulated in a dose-dependent manner when grown in the presence of exogenous TGF-alpha. Growth in 4 of 5 cell lines capable of serum-free propagation was inhibited from 28 to 56% when cultured in medium containing a TGF-alpha-neutralizing monoclonal antibody. These results support the view that TGF-alpha is an autocrine growth factor for cell lines derived from ovarian cancers of epithelial origin and suggest a potential role for TGF-alpha in the pathogenesis or progression of the disease.
Cell Division↗
Generation and characterization of a human chromosome 9 cosmid library.
A cosmid library has been constructed from the hamster-human hybrid cell line PK-87-9, which contains chromosome 9 as its sole known human component. Ten thousand colonies were produced, of which approximately 200, or 2%, contain human material. Fifty of these 200 were regionally mapped by an Alu-primed PCR product hybridization procedure. These cosmids were localized to all regions of chromosome 9, but were especially concentrated in the distal portion of 9q. The map location derived by the Alu-primed PCR product hybridization procedure was compared to the map location derived by fluorescent in situ hybridization. Assignment of chromosomal location by the two methods was correspondent in all but a few cases. The presumptive presence of HTF islands was investigated for 130 cosmids by digestion with the restriction enzyme NotI. Twenty percent of cosmids contained at least one NotI site. A number of simple sequence repeat polymorphisms identified from the cosmid set were characterized and will provide a link between the genetic and physical maps for this chromosome.
Animals↗
Construction and characterization of radiation hybrids for chromosome 9, and their use in mapping cosmid probes on the chromosome.
Radiation hybrids were produced from a monochromosomal microcell hybrid (PK87-9) which contains only human chromosome 9 with an inserted marker on 9p. Doses of radiation ranging from 1000 to 8000 rads were used to produce a series of hybrids with different size fragments of human chromosome 9. The inserted dominant selectable marker was used to select for hybrids that preferentially maintain fragments of 9p. A panel of 53 radiation hybrids were characterized for 17 chromosome 9 markers. In addition, 17 hybrids were analyzed by fluorescent in situ hybridization (FISH). Hybrids were produced with breaks on both 9p and 9q, many of which appear to contain a single fragment of human chromosome 9. These hybrid cell lines were used to regionally localize 31 cosmids isolated from a chromosome 9 cosmid library. Six cosmids were mapped to intervals on 9p, six cosmids mapped to the centromeric region of the chromosome, and 19 mapped to 9q.
Animals↗
Laparoscopic surgical technique for internal drainage of pelvic lymphocele.
A previously unreported technique of internal drainage of a pelvic lymphocele is described using a laparoscopic approach to create the peritoneal window for drainage in 2 patients. The technique avoids a larger incision and permits a shorter recovery period.
Aged↗
Pharmacology of smooth muscle cell replication.
The suggestion that smooth muscle cell proliferation contributes to hypertension, atherosclerosis, and restenosis after angioplasty has led to a growing interest in the use of drugs to inhibit this process. This review summarizes pharmacological studies of smooth muscle cell proliferation in vitro and in vivo and identifies specific mediators of proliferation that are implicated by drugs binding with high affinity to enzymes or receptors.
Animals↗
Heparin inhibits the expression of tissue-type plasminogen activator by smooth muscle cells in injured rat carotid artery.
Smooth muscle cells (SMCs) in balloon-injured rat carotid artery express tissue-type plasminogen activator (t-PA) at a time when they are migrating from the media to the intima. Since heparin inhibits SMC migration and intimal thickening, we have examined the possibility that heparin might also inhibit t-PA expression. Heparin (nonanticoagulant fraction; molecular weight, approximately 6,000) was administered by continuous intravenous infusion (1.0 mg/kg per hour) to Sprague-Dawley rats subjected to balloon injury of the left common carotid artery. At various times up to 14 days after injury, plasminogen activator expression was analyzed by zymography, plasmin generation, enzyme-linked immunosorbent assay, Northern blotting, and in situ hybridization. This dose of heparin inhibited SMC accumulation at 14 days by 60%. Both urokinase plasminogen activator (u-PA) and t-PA activity increased in injured arteries and reached a maximum at 7 days. Heparin treatment decreased t-PA, but not u-PA, activity. Total t-PA protein was decreased by treatment with heparin but not chondroitin sulfate, and the decrease in t-PA protein was associated with decreased t-PA mRNA in the media. These results in the injured rat carotid artery agree with our earlier observations that heparin inhibits t-PA gene expression in cultured baboon aortic SMCs. They also provide support for the hypothesis that heparin interferes with the expression of certain proteases required for SMC migration and proliferation.
Animals↗
S. cerevisiae alpha pheromone receptors activate a novel signal transduction pathway for mating partner discrimination.
Wild-type S. cerevisiae cells of both mating types prefer partners producing high levels of pheromone and mate very infrequently to cells producing no pheromone. However, some mutants that are supersensitive to pheromone lack this ability to discriminate. In this study, we provide evidence for a novel role of alpha pheromone receptors in mating partner discrimination that is independent of the known G protein-mediated signal transduction pathway. Furthermore, in response to pheromone, receptors become localized to the emerging region of morphogenesis that is positioned adjacent to the nucleus, suggesting that receptor localization may be involved in mating partner discrimination. Actin, myosin 2, and clathrin heavy chain are involved in mating partner discrimination, since strains carrying mutations in the genes encoding these proteins result in a small but significant defect in mating partner discrimination.
Actins↗
Comparison between electric toothbrushing and manual toothbrushing, with and without oral irrigation, for oral hygiene of orthodontic patients.
This study evaluated the effectiveness of one electric toothbrush and oral irrigation system in comparison with manual toothbrushing in 20 orthodontic patients. Twenty patients performed four oral hygiene routines for at least 4 weeks each. The routines included manual toothbrushing alone, electric toothbrushing alone, manual toothbrushing plus irrigation, and electric toothbrushing plus irrigation. Baseline plaque and gingival scores were recorded, and both indices were again recorded after each routine. The index used to evaluate gingival health was a slight modification of the Silness and Löe gingival index, while the plaque index was similar to the patient hygiene performance (PHP) index developed by Podshadley and Haley. The average overall scores for plaque and gingival condition for all patients who used each of the four oral hygiene routines were compared with a repeated-measures, analysis-of-variance statistical evaluation. The values obtained from the analysis showed that there were no significant differences between the means for plaque and gingival health in each group. The probabilities that these conclusions are incorrect are 18% for plaque and 2% for gingival health. Testing for validity of the data was done by more than one researcher, with consistent results.
Adolescent↗
Courtship in S. cerevisiae: both cell types choose mating partners by responding to the strongest pheromone signal.
We demonstrate that during the courtship stage of conjugation, S. cerevisiae a cells choose the alpha cell producing the highest level of pheromone from among potential mating partners. From this result and that for alpha cells we conclude that both a and alpha cells act as signaling cells during courtship, that both cell types respond by discriminating different levels of signal, and that the signals are the mating pheromones. Responding cells that are supersensitive to signal fail to discriminate pheromone-producing from nonproducing cells to an extent that depends on their degree of supersensitivity. We propose that partner selection in S. cerevisiae results from polarized morphogenesis of a responding cell in the direction of highest pheromone concentration and that cells defective in discriminating this gradient execute a default pathway in which an adjacent cell is selected at random.
Conjugation, Genetic↗
Applications of multinuclear NMR in the solid state to structural and dynamical problems in macromolecular chemistry.
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Biopolymers↗
The role of renal autotransplantation in complex urological reconstruction.
From 1972 to 1988, 108 patients underwent renal autotransplantation for renal artery disease (67), ureteral replacement (27), or renal cell carcinoma present bilaterally or in a solitary kidney (14). The most common indication for renal autotransplantation was to allow extracorporeal repair of complex branch renal artery lesions. Of the 54 patients in this group technically satisfactory branch renal arterial reconstruction and a successful clinical outcome were achieved in 52 (96%). Renal autotransplantation is the treatment of choice in these patients and also in selected children with main renal artery disease. Renal autotransplantation provided excellent results in 25 of 27 patients (92%) who required replacement of all or a major portion of the ureter. Over-all renal function was well preserved in these patients and only 1 has experienced chronic bacteriuria. Renal autotransplantation is a useful alternative to ileal interposition in this setting. Extracorporeal partial nephrectomy and renal autotransplantation were successful in 12 of 14 patients (85%) undergoing a nephron-sparing operation for renal cell carcinoma. In situ techniques are associated with less morbidity and currently are preferred in this group.
Adolescent↗
Courtship in Saccharomyces cerevisiae: an early cell-cell interaction during mating.
During conjugation in Saccharomyces cerevisiae, two cells of opposite mating type (MATa and MAT alpha) fuse to form a diploid zygote. Conjugation requires that each cell locate an appropriate mating partner. To investigate how yeast cells select a mating partner, we developed a competition mating assay in which wild-type MAT alpha cells have a choice of two MATa cell mating partners. We first demonstrated that sterile MAT alpha 1 cells (expressing no a- or alpha-specific gene products) do not compete with fertile MATa cells in the assay; hence, wild-type MATa and MAT alpha cells can efficiently locate an appropriate mating partner. Second, we showed that a MATa strain need not be fertile to compete with a fertile MATa strain in the assay. This result defines an early step in conjugation, which we term courtship. We showed that the ability to agglutinate is not necessary in MATa cells for courtship but that production of a-pheromone and response to alpha-pheromone are necessary. Thus, MATa cells must not only transmit but must also receive and then respond to information for effective courtship; hence, there is a "conversation" between the courting cells. We showed that the only alpha-pheromone-induced response necessary in MATa cells for courtship is production of a-pheromone. In all cases tested, a strain producing a higher level of a-pheromone was more proficient in courtship than one producing a lower level. We propose that during courtship, a MAT alpha cell selects the adjacent MATa cell producing the highest level of a-pheromone.
Blotting, Northern↗
Factors controlling growth of arterial cells following injury.
The proliferation of vascular smooth muscle cells is a key event in the development of arterial lesions. In experimental models, loss of arterial endothelium followed by platelet adherence does not necessarily stimulate smooth muscle cell proliferation. Furthermore, using animals deficient in platelets, smooth muscle cell proliferation was induced to an equal extent as in control animals following injury with a balloon catheter. Modulation of the smooth muscle response, however, was achieved by totally denuding arteries with a technique which did not traumatize medial cells. These data suggested that injury and cell death might induce proliferation of cells by release of endogenous mitogen. Basic FGF is present in the arterial wall and addition of this mitogen to denuded arteries was found to cause a highly significant increase in smooth muscle cell proliferation. These studies suggest that smooth muscle cell proliferation could be induced by factors present in the arterial wall and does not require exogenous factors. Smooth muscle cell proliferation following balloon catheter injury is significantly reduced by administration of calcium antagonists. Repeated administration of nifedipine caused a significant reduction in intimal lesion size induced by injury. The anti-proliferative effect was not observed in other tissues. Influx of Ca++ ions into medial smooth muscle cells may therefore be an obligatory step for replication.
Animals↗
Carbon-13 NMR of glycogen: hydration response studied by using solids methods.
The carbon-13 NMR spectra of glycogen are reported by using the methods of magic-angle sample spinning and high-power proton decoupling to provide a dynamic report on the glucose monomer behavior as a function of hydration. Although the glycogen behaves as a typical polymer in the dry state, addition of water makes a significant difference in the spectral appearance. Water addition decreases the carbon spin-lattice relaxation times by 2 orders of magnitude over the range from 7% to 70% water by weight. The proton-carbon dipole-dipole coupling, which broadens the carbon spectrum and permits cross-polarization spectroscopy, is lost with increasing hydration over this range. By 60% water by weight, scalar decoupling methods are sufficient to achieve a reasonably high-resolution spectrum. Further, at this concentration, the carbon spin-lattice relaxation times are near their minimum values at a resonance frequency of 50.3 MHz, making acquisition of carbon spectra relatively insensitive to intensity distortions associated with saturation effects. Though motional averaging places the spectrum in the solution phase limit, the static spectrum shows a residual broader component that would not necessarily be detected readily by using high-resolution liquid-state experiments.
Glycogen↗
Mechanism of antiatherogenic action of calcium antagonists.
Analysis of literature reports on the actions of calcium antagonists on the progression of experimental arterial disease has revealed a significant association between efficacy and time of commencement of administration. In the majority of studies where commencement of administration of calcium antagonists preceded or coincided with initiation of atherogenesis, suppression of atherosclerotic changes has been observed. Where administration commenced after initiation of atherogenesis, suppression of atherosclerotic changes has rarely been seen. This distribution of results strongly suggests that calcium antagonists inhibit a process occurring early in atherogenesis. We have previously shown that calcium antagonists selectively inhibit the proliferation of smooth muscle cells that occurs in response to balloon catheter injury. We report here further investigations into this effect, using nifedipine. In the rat there is a 'time window' for the antiproliferative action of nifedipine, between 8 and 30 h after balloon injury. In the rabbit, delaying nifedipine administration so that it commenced 7 days after balloon catheterisation abolished its antiproliferative effect. These results show that nifedipine inhibits smooth muscle cell proliferation at an early stage, probably during the G0/G1 phase of the cell cycle, and that after this time smooth muscle cells are refractory to its antiproliferative action. We conclude that the antiatherogenic actions of calcium antagonists in experimental models of arterial disease are the result of early inhibition of smooth muscle cell proliferation.
Animals↗
Recent results of cadaver kidney retransplantation.
The results of secondary cadaver renal transplantation in 42 patients treated from 1980 to 1986 have been reviewed. The initial graft was from a cadaver donor in all cases. All patients were managed with a maintenance immunosuppressive regimen, including either antilymphoblast globulin and/or cyclosporine. The over-all 1 and 2-year patient survival rates were 97 and 94 per cent, respectively. The over-all 1 and 2-year graft survival rates were 69 and 63 per cent, respectively. Graft success was not influenced by patient age greater than 50 years, diabetes, initial graft removal, interval between initial graft removal and retransplantation, duration of initial graft function, level of presensitization or HLA-Dr antigen matching. Currently, cadaver renal retransplantation can be performed safely and with an improved opportunity for graft success. Patients who return to dialysis after losing an allograft should be encouraged to consider another transplant for the same reasons that prompted initial transplantation.
Adolescent↗
Endoscopic correction of vesicoureteral reflux in the renal transplant candidate.
High grade vesicoureteral reflux is a well recognized risk factor for post-transplant infection that has been managed commonly with native nephrectomy. Recent reports have described the successful correction of vesicoureteral reflux by the subtrigonal injection of polytetrafluoroethylene (Teflon) paste. We treated 5 transplant candidates with vesicoureteral reflux with this technique. Ureteral reflux was corrected in 80 per cent of the treated ureters with 6 months of followup. Of the patients 3 have undergone successful renal transplantation without complication. This procedure is well suited to the end stage renal disease patient preparing for renal transplantation, since it avoids an open operation on the pre-transplant bladder and preserves the native kidney, thus, facilitating pretransplant dialysis.
Endoscopy↗