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Biomedical subjects

L J Goodman

Publications and source records attributed to L J Goodman.

At least 19 recordsLinked to original sources
PubMed1992

Differential transport and processing of variant mouse mammary tumor virus glycoproteins.

The transport and proteolytic processing of two individual gene isolates of the mouse mammary tumor virus (MMTV) glycoprotein were compared in transfected rat HTC hepatoma cells. Plasmids were constructed such that the MMTV glycoprotein genes were constitutively expressed from the promoter within the Rous Sarcoma Virus 5' Long Terminal Repeat in the absence of other MMTV proteins. An isolate of the GR strain MMTV glycoprotein was efficiently transported and processed resulting in the localization of MMTV glycoproteins at the cell surface and in the extracellular environment. Moreover, the kinetics of acquisition of endoglycosidase H resistant oligosaccharide side chains and the rate of endoproteolytic cleavage of the glycosylated polyprotein expressed in transfected cells were virtually identical to that observed in viral-infected rat hepatoma cells. In contrast, a natural variant of the C3H strain MMTV glycoprotein expressed in transfected cells was retained in an intracellular compartment by a heavy chain binding protein (BiP)-independent pathway in an endoglycosidase H sensitive and uncleaved form. This MMTV glycoprotein isolate was retained early in the exocytic pathway and displayed a half-life of approximately 45 min in transfected cells. Only a minor fraction of the expressed C3H variant glycoprotein was detected at the cell surface but was not externalized. Our results suggest that the variant C3H MMTV glycoprotein contains one or more mutations that preclude its efficient transport through the exocytic pathway.

Animals↗
PubMed1992

High-level quinolone resistance in clinical isolates of Campylobacter jejuni.

During a recent clinical trial of ciprofloxacin in the therapy of acute diarrhea, two subjects infected with Campylobacter jejuni who received ciprofloxacin failed microbiologically and one also failed clinically. Although both pretreatment isolates were susceptible to ciprofloxacin, the posttreatment isolates were resistant to ciprofloxacin (MIC = 32 micrograms/ml) and to other quinolones. The posttreatment isolates remained susceptible to nonquinolone antimicrobials. DNA gyrase holoenzyme was isolated from one of the resistant posttreatment isolates and was 8- to 16-fold less sensitive to inhibition by ciprofloxacin than was the gyrase from the paired pretreatment susceptible isolate. Ciprofloxacin accumulation was diminished in the two resistant posttreatment isolates. These results show that mutation in C. jejuni can occur in vivo and is associated with clinically significant resistance to the newer quinolones.

Anti-Infective Agents↗
PubMed1992

Using a database to analyze core basic science content in a problem-based curriculum.

As medical schools critically reevaluate their methods of instruction and as the number of innovative programs increases, the content delivered across disciplines must be carefully reviewed. However, few methods of content analysis have been applied to problem-based programs. In 1989-90 and 1990-91, the authors analyzed the distribution of basic science content in the 53 cases in the problem-based curriculum of Rush Medical College of Rush University. They developed a content vocabulary and created a database using a widely available computer software program. The content areas specific to each case were identified by faculty using the content vocabulary. To determine whether these content areas were actually identified by the students participating in the problem-solving sessions, the authors surveyed the 36 student participants in the classes of 1993 and 1994 and also interviewed the 15 faculty facilitators of the sessions. The surveys and interviews demonstrated that over 90% of the content areas identified by the faculty were actually covered by the students. The authors conclude that the database assists in their review of the curriculum for omission and redundancy. Other uses and limitations of this method are also discussed.

Biological Science Disciplines↗
PubMed1991

An experiment in medical education. A critical analysis using traditional criteria.

In 1984, in addition to its standard traditional curriculum, Rush Medical College (Chicago, Ill) developed a Socratic problem-based method of teaching basic science material called the alternative curriculum. As part of an evaluation of this new curriculum, students in the two curricula were compared using three traditional measurements: (1) test scores from the National Board of Medical Examiners, Part I; (2) test scores from the National Board of Medical Examiners, Part II; and (3) performance on an oral examination. Alternative curriculum students did not differ significantly from their traditional curriculum classmates on National Board of Medical Examiners, Part I and Part II total scores, although their subset scores on Part I did tend to be lower, reaching significance in one subset area. Differences in performance favoring the traditional curriculum were primarily seen in the early years of the program. Alternative curriculum students in the class matriculated in 1987 scored significantly higher in three of five categories on the oral examination.

Adult↗
PubMed1991

Altered effects of glucocorticoids on the trafficking and processing of mouse mammary tumor virus glycoproteins constitutively expressed in rat hepatoma cells in the absence of nonglycosylated viral components.

We have documented previously that glucocorticoid hormones modulate the posttranslational localization of cell surface mouse mammary tumor virus (MMTV) glycoproteins in the viral-infected M1.54 rat HTC hepatoma cell line. To determine whether glucocorticoids affect the trafficking of individually synthesized MMTV glycoproteins, HTC cells were transfected with a constitutively expressed MMTV glycoprotein gene lacking the viral phosphoprotein and polymerase genes. This construct also allows equivalent levels of MMTV glycoproteins to be compared in the presence or absence of glucocorticoids. Indirect immunofluorescence and immunoprecipitation of radiolabeled cells revealed that in transfected cells the transmembrane MMTV glycoproteins are efficiently expressed, transported to the cell surface, and proteolytically cleaved in the presence or in the absence of the synthetic glucocorticoid dexamethasone. Cell surface immunoprecipitation of [35S]methionine-labeled cells showed that the level of plasma membrane gp78 appeared to be stimulated 2-fold after dexamethasone treatment, even though fluorescence-activated cell sorting revealed no discernible change in the total concentration of cell surface MMTV glycoproteins. Analysis of oligosaccharide side chain maturation through a pulse-chase radiolabeling revealed that the rate of rough endoplasmic reticulum-Golgi transport was essentially identical in dexamethasone-treated and untreated transfected cells and was similar to that observed in dexamethasone-treated M1.54 cells. Thus, in contrast to viral-infected hepatoma cells, mostly constitutive cellular machinery mediates the trafficking and maturation of cell surface MMTV glycoproteins expressed outside of the proviral context. Taken together, our results suggest that the glucocorticoid-stimulated synthesis of nonglycosylated viral components may contribute to or be responsible for the regulated trafficking of MMTV glycoproteins observed in viral-infected rat hepatoma cells.

Amino Acid Sequence↗
PubMed1991

Evidence for a protein-trafficking gene that rescues the defective glucocorticoid-regulated transport and Golgi retention of mouse mammary tumor virus glycoproteins in a rat hepatoma cell-sorting variant.

Glucocorticoids regulate the trafficking of cell surface mouse mammary tumor virus (MMTV) glycoproteins in the virus-infected rat hepatoma cell line M1.54. The CR4 rat hepatoma sorting variant, which is derived from M1.54 cells by immunoselection, is uniquely defective in the glucocorticoid-regulated transport of MMTV glycoproteins. Indirect immunofluorescence of fixed permeabilized cells and subcellular fractionation of isolated microsomes revealed that variant CR4 cells retain the MMTV glycoproteins in Golgi-like membranes after glucocorticoid treatment. The variant CR4 phenotype can be complemented by interspecies cell fusions with human HepG2 hepatoma cells and by DNA rescue with genomic fragments isolated from either human or rat hepatoma cells. Transfected wild-type genomic fragments rescue the sorting defect in CR4 at a frequency consistant with a single genetic locus, whereas homologous transfection with CR4 genomic DNA has no effect. Thus, complementation of a rat hepatoma cell-sorting variant supports the existence of a novel protein-trafficking activity encoded by the human or rat genomes that acts in trans in the Golgi to selectively mediate the sorting of cell surface MMTV glycoproteins in glucocorticoid-treated cells.

Animals↗
PubMed1990

Empiric antimicrobial therapy of domestically acquired acute diarrhea in urban adults.

From June 1985 to September 1987, 202 adults were enrolled in a randomized, double-blinded study comparing ciprofloxacin (500 mg) with sulfamethoxazole and trimethoprim (160 mg/800 mg) or placebo for adults with acute diarrhea. All patients were treated on the day of presentation and received medication on a twice-daily schedule (every 12 hours) for 5 days. Bacterial isolates from these patients included 35 Campylobacter, 18 Shigella, and 15 Salmonella. Treatment at the time of presentation with ciprofloxacin compared with placebo shortened the duration of diarrhea (2.4 vs 3.4 days), and increased the percentage of patients cured or improved by treatment days 1, 3, 4, and 5. Similar significant differences for sulfamethoxazole and trimethoprim compared with placebo were not seen.

Adult↗
PubMed1989

In vitro activities of lomefloxacin and temafloxacin against pathogens causing diarrhea.

The in vitro activities of temafloxacin (A63004) and lomefloxacin (SC-47111; NY-198) were compared with those of seven other antibiotics against 146 isolates of bacterial enteric pathogens, including Campylobacter jejuni and Campylobacter coli. Ciprofloxacin was the most active drug against the Salmonella, Shigella, Yersinia, and Vibrio spp. tested. Lomefloxacin, temafloxacin, and difloxacin were the most active drugs tested against Campylobacter spp. (MIC for 90% of strains, 0.125 to 0.25 micrograms/ml).

4-Quinolones↗
PubMed1989

Glucocorticoid-regulated and constitutive trafficking of proteolytically processed cell surface-associated glycoproteins in wild type and variant rat hepatoma cells.

Glucocorticoids regulate the trafficking of mouse mammary tumor virus (MMTV) glycoproteins to the cell surface in the rat hepatoma cell line M1.54, but not in the immunoselected sorting variant CR4. To compare the localization of MMTV glycoproteins to another proteolytically processed glycoprotein, both wild type M1.54 cells and variant CR4 cells were transfected with a human insulin receptor (hIR) expression vector, pRSVhIR. The production of cell surface hIR was monitored in dexamethasone-treated and -untreated wild type M1.54 and variant CR4 cells by indirect immunofluorescence, direct plasma membrane immunoprecipitation, and by [125I] insulin binding. In both wild type and variant rat hepatoma cells, hIR were localized at the cell surface in the presence or in the absence of 1 microM dexamethasone. In contrast, the glucocorticoid-regulated trafficking of cell surface MMTV glycoproteins occurred only in wild type M1.54 cells. We conclude that the hIR, which undergoes posttranslational processing reactions similar to MMTV glycoproteins, does not require glucocorticoids to be transported to the plasma membrane and is representative of a subset of cell surface glycoproteins whose trafficking is constitutive in rat hepatoma cells. Thus, MMTV glycoproteins and hIR provide specific cell surface markers to characterize the glucocorticoid-regulated and constitutive sorting pathways.

Animals↗
PubMed1989

Medicare recoupment: a legal and legislative update.

In 1987, the Texas Medical Association and 20 other plaintiffs filed suit against the US Department of Health and Human Services (HHS) over the federal government's effort to recoup $14 million from physicians and patients for alleged overpayments during July 1985 through March 31, 1986. A federal district court judge granted a preliminary injunction that halted the recoupment pending a full hearing on the merits of the case and a decision. In June 1989 the Court of Appeals overturned the district court's decision, and TMA turned to the US Congress for relief. This article summarizes recent judicial and legislative progress in halting the recoupment.

Medicare↗