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Biomedical subjects

R Cote

Publications and source records attributed to R Cote.

34 records · Page 2Linked to original sources

Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.

To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: "suspension transduction" and "stromal growth factor transduction." However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Two molecular pathways to transitional cell carcinoma of the bladder.

Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.

Alleles↗

Expression of c-kit and kit ligand proteins in normal human tissues.

The c-kit receptor and its cognate ligand, KL, play a critical role in melanogenesis, gametogenesis, and hematopoiesis. Studies on the expression of c-kit and KL have been primarily focused on mouse development. We undertook the present study to characterize the pattern of expression of these molecules in normal adult human tissues. Using immunohistochemistry and consecutive tissue sections from the same block, we evaluated a variety of well-preserved normal tissues for c-kit and KL microanatomic distribution. c-kit protein was identified in tissue mast cells, melanocytes, glandular epithelial cells of breast, parotid, dermal sweat, and esophageal glands. Scattered c-kit immunoreactivity was also observed for testicular and ovarian interstitial cells. A striking regional distribution of c-kit was detected in the central nervous system, particularly in the cerebellum, hippocampus, and dorsal horn of the spinal cord. KL protein was identified in cells complementary to staining for the receptor, such as glandular myoepithelium of breast and sweat glands. Intense KL immunoreactivity was observed in smooth muscle cells of the bladder, cervix, uterus, and gastrointestinal tract, as well as in striated and cardiac muscle. Strong KL staining was also detected in prostate fibromuscular stroma cells. In the central nervous system, KL expression was confined to Golgi and Purkinje cells in the cerebellum. These results suggest a role for this receptor and its ligand in the maintenance of a variety of fully differentiated tissues.

Brain Chemistry↗

[Quantitative scales for measuring neurological deficit in cerebrovascular diseases].

The development of quantitative scales for the measurement of neurological deficit is a complex process involving the assessment of both validity and reliability. The steps required in the validation and reliability assessment are outlined in this paper. Each component of the process is illustrated using the results of the validation of the Canadian Stroke Scale (CNS).

Cerebrovascular Disorders↗

A comparison of motility: autogenous dermis-fat vs synthetic spherical implants.

The socket and prosthesis motility and the forniceal depths in a group of 47 patients who had undergone enucleation and implantation of synthetic spherical implants were compared with those in a group of 34 patients who had undergone enucleation and implantation of autogenous dermis-fat orbital implants. The primary autogenous dermis-fat orbital implants provided greater socket movement and deeper fornices than the synthetic spherical implants. Prosthesis motility, however, was the same in the two groups.

Adipose Tissue↗

Dietary potassium and heavy exercise: effects on muscle water and electrolytes.

Eight men were studied during two 4-day exercise-dietary regimens, once under a control diet (80 mEq K+/day) and again with a diet low in K+ (25 mEq/day). Muscle K+ increased 5 to 6% as a result of the two exercise-dietary regimens, while no change was observed for muscle Na+ or Mg++. Plasma volume increased throughout the 4 days of each exercise-diet sequence, with the low K+ regimen resulting in the largest plasma volume gain (+15%) and a marked reduction in urinary K+ excretion. Despite the losses of K+ in sweat and the low K+ intake, there was a relatively small decrease in total body K+ content (less than 2% of body content). Based on these measurements of extracellular (plasma) and tissue (muscle) water and electrolytes, we have concluded that in combination with 4 days of heavy exercise and sweating, a low K+ diet will not significantly diminish the total body K+ content.

Adult↗

Urodynamics studies in benign prostatic hypertrophy.

A study of patients with benign prostatic hypertrophy indicates that flow rates may well be useful in evaluating the degree of obstruction and the results of therapy. Electromyography and cytometry studies, while demonstrating certain tendencies in benign prostatic hypertrophy, do not give statistically significant data for evaluation and prognostication either by themselves or when correlated with radiographic changes and flow rates.

Humans↗

Isolation and characterization of rifampin-resistant and streptolydigin-resistant mutants of Bacillus subtilis with altered sporulation properties.

Mutants of Bacillus subtilis with altered deoxyribonucleic-dependent ribonucleic acid polymerase activity have been isolated and characterized. These mutants, selected as strains resistant to rifampin or streptolydigin, demonstrate drug-resistant in vitro ribonucleic acid synthesis. Sporeforming ability and support of phage infection are altered in many of the mutants. Mutations to rifampin and streptolydigin resistance have been located on the B. subtilis chromosome and ordered relative to the markers cysA14 and str.

Alkanesulfonates↗

Significance of carotid restenosis following endarterectomy.

BACKGROUND AND PURPOSE: The clinical significance of restenosis after carotid endarterectomy as detected by duplex ultrasound has not been clearly established. To address this problem, we retrospectively evaluated the experience at two university-affiliated hospitals. METHODS: All charts of patients with carotid endarterectomies between June 1987 and April 1995 were reviewed. Inclusion required neurological assessment and postoperative duplex ultrasound. Exclusion was based on a known source of cardioembolic disease, or recent (<6 months) myocardial infarction. Primary clinical endpoints were ipsilateral transient ischemic attack (TIA) or ischemic stroke. Contributing vascular risk factors were also identified. The effect of restenosis on event-free survival was analyzed using life tables and Gehan-Wilcoxon rank sum tet. Logistic regression was used to identify independent risk factors for restenosis and vascular events. RESULTS: One hundred and eighty-seven patients were identified who underwent a total of 207 endarterectomies. Mean follow-up was 30.4 +/- 20.9 months during which a total of 64 vascular events, including 42 TIAs, 18 strokes, and 4 vascular deaths occurred. Of these 21 TIAs and 8 strokes were ipsilateral to the side of endarterectomy. Event rates were compared for patients with ipsilateral high- (>/=50%) and low-grade (<50%) restenosis. These two groups were comparable in terms of baseline risk factors. There was no significant difference in vascular event rates (for either ipsilateral events or events in any vascular territory) between the group with high- and low-grade restenosis. Nor was any such difference in event rates shown for patients who showed ipsilateral progression of carotid disease on serial ultrasound. However, patients operated for symptomatic carotid disease had a significantly higher risk of neurological events (p = 0.035). Logistic regression failed to disclose any other risk factors that were independently predictive of either restenosis or vascular events during follow-up. CONCLUSION: This study does not show a difference in vascular event rates for higher grades of carotid restenosis after carotid endarterectomy. Routine surveillance with carotid ultrasound does not appear to identify patients at higher risk for postoperative cerebrovascular events.

Carotid Artery, Internal↗

Internal carotid occlusion: a prospective study.

Forty-seven patients with ICA occlusion and who presented either without any or only a mild neurological deficit were prospectively followed for an average of 34.4 months. During this period of time, 11 patients (23.5%) suffered a cerebral infarction of which two-thirds were ipsilateral to the occluded artery. The stroke rate distal to an occluded ICA artery was 5% per year. Twenty-four patients (51%) continued to experience TIA's in the territory of the occluded artery. The mortality rate was low (8.5%) during follow-up. Whether extracranial-intracranial bypass surgery will decrease the risk of cerebral infarction in this subgroup of patients is unknown. The International EC/IC Collaborative Trial may elucidate this point because this subgroup represents one of the randomization strata of that study.

Adult↗

Cytotoxic effects of MGI 114 are independent of tumor p53 or p21 expression.

MGI 114, an analog of illudin S, shows potent activity against a broad range of human tumors in vitro and in vivo, including drug resistant tumors. In this study we examined cytotoxicity of MGI 114 against human tumor cell lines (MCF7, MDA.MB.468, EJ1, J82, SCaBER, KG-1, HL60, and IMR-90) with differing expression of p53 and/or p21 (WAF1) tumor suppressor genes. Only MCF7 and IMR-90 express the wild type p53, WAF1 is present in high levels in MCF7 and SCaBER. WAF1 expression can be induced in KG-1, HL60, and IMR-90. The cells were treated with MGI 114 at 0.1, 1.0 and 10 micrograms/ml in 1 h exposure and with 0.01, 0.1 and 1.0 microgram/ml MGI 114 in a continuous exposure. Cell numbers were measured at days 2, 4, and 7. MGI 114 suppressed growth in all cell lines at day 2 after 1 h exposure at the two highest concentrations and at all concentrations in a continuous exposure. Some cells partly recovered from the inhibition by day 4. Expression of WAF1 had no apparent effect on growth suppression by MGI 114, however, cells with inducible WAF1 showed slower recovery from MGI 114 inhibition in comparison with the cells under non-permissive conditions. Overall, MGI 114 effectively inhibited growth of human cancer cells regardless of their p53 and WAF1 status.

Antineoplastic Agents↗