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Biomedical subjects

L A Collins

Publications and source records attributed to L A Collins.

33 records · Page 2Linked to original sources
PubMed1994

Risk factors for invasive fungal infections complicating orthotopic liver transplantation.

Risk factors for invasive fungal infection in patients undergoing orthotopic liver transplantation were examined. Thirty-four of 168 transplants were complicated within 100 days after transplantation by documented invasive fungal infection (Candida species, 28 patients; mycelial fungi, 5; both Candida and Aspergillus species, 1). In the multivariate Cox proportional hazards model, three baseline and two posttransplant variables were independently significant risk factors for infection: level of creatinine (hazard ratio = 1.4), length of transplant operation (HR = 1.2), retransplantation (HR = 3.2), abdominal or intrathoracic reoperations (HR = 2.5), and cytomegalovirus infection (HR = 8.5). Four predictors (creatinine of > 3.0 mg/dL, operative time of > or = 11 h, retransplantation, and early colonization) assessable at the time of transplantation or shortly thereafter were incorporated into a simple predictive model for risk stratification. The risk of invasive fungal infection ranged from 1% in patients with no predictors to 67% in patients with two or more predictors. Strategies to prevent invasive fungal infections after liver transplantation should be targeted to these high-risk groups.

Adrenal Cortex Hormones↗
PubMed1993

Combined antiproliferative activity of 5-fluorouracil and mitomycin-C against primary human ovarian tumors and cell lines in a clonogenic assay.

Ovarian tumors from 389 patients were successfully grown in a human tumor clonogenic assay (HTCA). Specimens from patients with or without prior chemotherapy showed similar chemosensitivity patterns. Excluding drugs commonly used for first-line chemotherapy, 5-fluorouracil (5-FU) and mitomycin-C (MMC) are among the active second-line agents, based upon HCTA data. Using this in vitro information from primary tumor specimens, two human ovarian cancer cell lines were used to study in detail the interactions of combined 5-FU and MMC. Drug scheduling which maximized combined antitumor activity was studied. Combined 5-FU and MMC revealed positive drug interactions most consistently when both drugs were used simultaneously with long-term exposure. Pulse treatment with MMC (1 hr) followed by continuous 5-FU exposure resulted in slightly less additive interaction than simultaneous long-term exposure. Pretreatment with 5-FU followed by a continuous exposure to MMC was as effective as the simultaneous method, as long as MMC was added within an 8-hr interval. Drug schedule dependency was examined, revealing that MMC, as a single agent, is both dose and schedule dependent. The results of these in vitro studies suggest that: (1) exposure to prior chemotherapy does not induce demonstrable pleiotropic drug resistance in these ovarian cancers tested; and (2) combined 5-FU and MMC show positive interactions against ovarian cancer cell lines, with optimal scheduling seeming to be long-term simultaneous exposure to both MMC and 5-FU.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

In vitro activity of RP59500, an injectable streptogramin antibiotic, against vancomycin-resistant gram-positive organisms.

The in vitro activity of RP59500, a streptogramin antibiotic, against 146 clinical isolates of vancomycin-resistant gram-positive bacteria was examined. Five strains of the species Enterococcus casseliflavus and Enterococcus gallinarum, for which the MIC of vancomycin was 8 micrograms/ml, were also studied. Twenty-eight vancomycin-susceptible strains of Enterococcus faecalis and Enterococcus faecium were included for comparison. The drug was highly active against Leuconostoc spp., Lactobacillus spp., and Pediococcus spp. (MICs, < or = 2 micrograms/ml). RP59500 was more active against vancomycin-susceptible strains of E. faecium than E. faecalis (MICs for 90% of the strains [MIC90s], 1.0 versus 32 micrograms/ml). Vancomycin-resistant strains of E. faecalis were as resistant to RP59500 as vancomycin-susceptible strains (MIC90, 32 micrograms/ml), but some vancomycin-resistant E. faecium strains were relatively more resistant to the new agent (MIC90, 16; MIC range, 0.5 to 32 micrograms/ml) than were vancomycin-susceptible organisms of this species.

Drug Resistance, Microbial↗
PubMed1993

In vitro activity of ramoplanin against vancomycin-resistant gram-positive organisms.

In vitro activity of ramoplanin, a cyclic lipoglycopeptide, against 92 vancomycin-resistant gram-positive organisms was evaluated. Ramoplanin demonstrated potent activity against many highly vancomycin-resistant organisms including enterococci (MICs for 90% of strains tested of 0.5 micrograms/ml) and against Lactobacillus spp., Leuconostoc spp., and Pediococcus spp., all of which were inhibited at concentrations of < or = 0.25 micrograms/ml. This drug or a derivative compound merits further investigation as a potential therapeutic agent for infections due to vancomycin-resistant enterococci.

Anti-Bacterial Agents↗
PubMed1993

Renal angiotensin receptor mapping in obese spontaneously hypertensive rats.

Obese spontaneously hypertensive rats (SHR) develop nephropathy with severe proteinuria, but lean littermates do not develop renal disease. Intrarenal angiotensin has been suggested to contribute to nephropathy in other experimental models. We examined the regulation of angiotensin receptors as a reflection of target tissue response to possible changes in the renin-angiotensin system. We visualized angiotensin receptors in kidneys of 6-8-month-old obese SHR and their lean littermates. Both obese and lean rats were hypertensive as determined by tail-cuff or by direct measurement. Histologic studies showed early glomerular sclerosis in obese but not lean rats. Autoradiographic visualization of angiotensin receptor binding sites in both obese and lean SHR showed glomeruli and medullary rays having the highest levels of binding with additional diffuse labeling in cortex and outer medulla. In obese rats, binding was reduced relative to lean littermates, particularly in the medulla, while intense binding in glomeruli was preserved. Loss of receptors did not reflect tissue damage, since the medulla showed no pathological changes. Biochemical assays of the binding of subtype-selective antagonists to 125I-angiotensin sites in intact sections showed that both losartan-sensitive and PD 123319-sensitive sites were decreased in nephrotic obese rats. We conclude that specific binding sites for angiotensin are decreased in obese SHR with early glomerular sclerosis, suggesting that angiotensin receptors may be regulated by pathogenic processes in this model of renal disease.

Angiotensin II↗
PubMed1992

In vivo requirement of integration host factor for nar (nitrate reductase) operon expression in Escherichia coli K-12.

The nitrate reductase operon (narGHJI) of Escherichia coli encodes an anaerobic respiratory enzyme. Previous work has identified two cis-acting sites in the nar operon control region: a proximal site required for anaerobic induction mediated by the activator Fnr and a remote upstream site required for nitrate induction mediated by the activator NarL [Li, S. & DeMoss, J. A. (1988) J. Biol. Chem. 263, 13700-13705]. Our search for nar regulatory mutants yielded one strain with a mutation in himD, the structural gene for one of the subunits of integration host factor (IHF). Strains carrying null alleles of the IHF structural genes, himD and himA, had severe defects in nitrate induction of the nar operon but were normal for nitrate induction of the coordinately regulated fdn operon. Anaerobic expression of both operons was normal in him mutants. Gel-mobility-shift and DNase I protection experiments revealed a single IHF binding site in the nar operon control region, located midway between the upstream activation site and the promoter. We conclude that an IHF-mediated DNA bend is essential for efficient nitrate induction of the sigma 70-dependent nar operon promoter. This requirement of IHF for transcriptional activation had been noted for several sigma 54-dependent promoters.

Bacterial Proteins↗
PubMed1992

An in vitro thymidine incorporation assay for human cancers: technical details revisited.

Among the choices of laboratory methods for in vitro testing of human tumor chemosensitivity, a thymidine incorporation assay (TIA) has been described. Advantages of a TIA over a colony-forming assay include greater probability of tumor growth, requirement for fewer tumor cells, less dependence on an absolute single-cell suspension, shorter time to completion, and the ability to measure up to three logs cell-kill. Specific technical details which are reported in the literature for performing a TIA are incomplete and/or conflicting between one laboratory and another. This paper reports details of methods designed to remove unbound 3[H]-thymidine from the agarose, standardize background counts, and determine optimal cell-plating densities, labeling time, optimal concentration of 3[H]-thymidine, and the best day after seeding cultures to add the 3[H]-thymidine. Care has been taken to compare the end point of drug sensitivity determinations following these methodologic changes, both among serial TIAs as well as with colony-forming assays.

Cisplatin↗
PubMed1992

Mutational analysis reveals functional similarity between NARX, a nitrate sensor in Escherichia coli K-12, and the methyl-accepting chemotaxis proteins.

During anaerobic growth, nitrate induces synthesis of the anaerobic respiratory enzymes formate dehydrogenase-N and nitrate reductase. This induction is mediated by a transcription activator, the narL gene product. The narX gene product may be involved in sensing nitrate and phosphorylating NARL. We isolated narX mutants, designated narX*, that caused nitrate-independent expression of the formate dehydrogenase-N and nitrate reductase structural genes. We used lambda narX specialized transducing phage to genetically analyze these lesions in single copy. Two previously isolated narX* mutations, narX32 and narX71, were also constructed by site-specific mutagenesis. We found that each of these alleles caused nitrate-independent synthesis of formate dehydrogenase-N and nitrate reductase, and each was recessive to narX+. The narX* mutations lie in a region of similarity with the methyl-accepting chemotaxis protein Tsr. We suggest that the narX* proteins have lost a transmembrane signalling function such that phosphoprotein phosphatase activity is reduced relative to protein kinase activity.

Amino Acid Sequence↗
PubMed1991

Proliferative glomerulopathy following extracorporeal shock wave lithotripsy in the pig.

Histopathologic changes after extracorporeal shock wave lithotripsy (ESWL) were studied in kidneys from four groups of nine pigs treated with an EDAP LT-01 (five pigs/group) or Dornier HM3 (four pigs/group) lithotripter, and sacrificed at time zero, 48 hours, one week and one month. Treatment dosages increased consistently within each group. Samples from primary treatment area and opposite control kidney were processed routinely for light, immunofluorescence, and electron microscopy. Tubulointerstitial changes included hemorrhages at zero and 48 hours and scars at one week and one month with both lithotripters. Glomerular mesangial cell proliferation started by 48 hours and increased over one month in treated and control samples. Electron microscopy showed mesangial deposits and phagolysosomes. Immunofluorescence showed trace IgG, zero IgM, and 1-2+ C3. The conclusions were: 1) Mesangial cell proliferation associated with deposits of C3 and phagocytosis of cellular debris starts by 48 hours post ESWL and increases thereafter, with both Dornier and EDAP lithotripters. 2) The pathogenesis appears to involve phagocytosis of circulating cellular debris and red blood cell fragments presumed to derive from breakdown of the hematoma caused by the lithotripsy.

Animals↗
PubMed1989

Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors.

The potential significant therapeutic and prognostic roles for the sex steroid receptors in ovarian cancer are recognized. The authors present in detail the biochemical, morphologic, cytogenetic, and growth characteristics of an ovarian carcinoma cell line, BG-1, which has functional estrogen and progesterone receptors (23 and 300 fmol/mg protein, respectively) in clinically significant levels. In particular, BG-1 has a DNA index of 1.14, a stable karyotype with specific translocations, and produces and secretes CA 125 into the media.

Adenocarcinoma↗
PubMed1989

Initial EDAP LT-01 lithotripsy group experience in the United States.

The initial United States cooperative experience with the EDAP LT-01 second generation piezoelectric extracorporeal shock wave lithotriptor using ultrasonic guidance is presented. Particular to the machine are lack of radiation exposure, no need for anesthesia, a purely outpatient procedure, no electrocardiographic problems, a high degree of safety and a paucity of complications. The equipment is described briefly. The same machine currently is being used to destroy renal and biliary stones. The results are encouraging and highly comparable to the initial experience with the earlier machines. Fragmentation rates are approximately 86%, with destruction rates of 63.4% over-all. Ultrasound localization and monitoring proved surprisingly easy to learn and were increasingly less of a problem as experience was gained. No serious complications were observed, and there were no renal losses and no deaths. Only 3 cases of steinstrasse were noted among 461 with 633 stones targeted during 595 treatments.

Adolescent↗
PubMed1988

Food-associated intoxicants.

The association of toxic substances with human foods has long been recognized. While intrinsic compounds appear during storage as a result of spoilage by chemical processes or by contamination with micro-organisms. In the numerous stages of food production from source to table there are many opportunities for contamination. This article reviews the wide spectrum of food-associated toxicants, outlining the mechanisms by which these substances reach the food products. To illustrate the diversity of these mechanisms, some notable examples of mass contamination of food are quoted. The presence of toxic substances in human food is, and will continue to be, a challenge for toxicologists, and a source of concern for the public, for industry, and for the scientific community.

Animals↗
PubMed1985

PMA induces the ligand-independent internalization of CR1 on human neutrophils.

Phorbol myristate acetate (PMA) has been reported to confer on the C3b receptor (CR1) of neutrophils a capacity for phagocytosis of particles bearing C3b without the involvement of other membrane receptors. In the present study, we employed a monoclonal antibody, YZ-1, that is specific for CR1 to assess the effect of PMA on plasma membrane expression of CR1, total cellular CR1, and internalization of CR1 by neutrophils. PMA had a biphasic effect on the membrane expression of CR1 by purified neutrophils, with 4 ng/ml inducing a 60% increment in receptor expression, and higher concentrations causing up to a 70% decrement. PMA-dependent increases in CR1 expression were not accompanied by corresponding changes in total cellular CR1 and were preempted by treatment of cells with formyl-methionyl-leucyl-phenylalanine (FMLP). PMA-induced decreases in CR1 expression by neutrophils, as measured by binding of indirectly fluoresceinated or radiolabeled YZ-1, or of 125I-labeled dimeric C3b, were maximal with 20 to 30 ng/ml PMA, and occurred within 30 min of incubation at 37 degrees C. The PMA-dependent down-regulation of CR1 by neutrophils was not associated with a comparable decrease in total cellular CR1, and this response was observed to occur also with monocytes but not with peripheral blood lymphocytes. By tagging neutrophil CR1 with 125I-YZ-1 Fab and monitoring accessibility to Protease, intracellular CR1 (inaccessible) was discriminated from receptor on plasma membrane (accessible). Internalization of CR1 occurred within 5 min after addition of PMA to neutrophils, was dose dependent, and involved up to two-thirds of the tagged receptors. Therefore, PMA caused internalization of CR1 by neutrophils in the absence of ligand, indicating that this response was independent of a transmembrane signal generated by a C3b-CR1 interaction.

Animals↗
PubMed1978

Ultrastructure of the foveal glands of the ticks, Dermacentor andersoni Stiles and D. variabilis (Say).

The foveal glands of Dermacentor variabilis appear to consist of 2 cell types. The outer cells (Type I) are active, with large areas of abundant finely granular material, apparently precursors of the mature secretory granules. The inner cells (Type II) are apparently storage cells. They are highly vacuolated and contain coarsely granular material as well as presumably mature secretory granules. The foveal glands of D. andersoni contain only Type II cells with extensive accumulations of presumably mature secretory granules.

Animals↗