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Biomedical subjects

J M Greene

Publications and source records attributed to J M Greene.

At least 55 records · Page 3Linked to original sources

Creation of a regional medical-nutrition education network.

The Southeastern Regional Medical-Nutrition Education Network (SER-MEN) was developed to coordinate and improve nutrition education in a consortium of the medical schools in Alabama, Florida, Georgia, and South Carolina. SERMEN's central office is at the Medical College of Georgia with the testing office at the University of Alabama at Birmingham. Students, faculty, and consultants in nutrition, education, and computer networking work together on projects on each campus that are coordinated and planned through semiannual meetings. A standardized examination was developed with the Nutrition Test-Item Bank to assess nutrition knowledge at various years of medical students from network schools. Each SERMEN school is connected to a microcomputer system at the central office that provides access to a data base of nutrition education and resources on each campus for developing curricula and syllabi. Funding has been provided by societies, foundations, and government agencies.

Computer Communication Networks↗

Activation and repression of mammalian gene expression by the c-myc protein.

One mechanism by which nuclear-localized oncogenes might transform cells is through an ability to regulate gene expression. We show that the c-myc protein stimulates the level of appropriately initiated expression from the human heat shock protein 70 (hsp70) promoter. Sequences required for full activation lie upstream of the transcription initiation site and are distinct from sequences necessary for basal expression. These sequences also appear distinct from promoter sequences necessary for heat induction, serum induction, and induction by the papovavirus T antigens. The c-myc protein inhibits appropriately initiated expression from the mouse metallothionein I (MT-I) promoter. A mutation that removes 138 amino acids of exon 2 produces a c-myc gene product that is capable of activating the hsp70 promoter but is no longer capable of inhibiting MT-I expression, suggesting that these two properties reside in different domains of the c-myc protein. Expression from the adenovirus EII promoter is slightly inhibited, while expression from the SV40 early promoter is minimally affected by the c-myc protein. Both the spectrum of promoters regulated by the c-myc protein and the sequence requirements for that regulation differ from those of previously characterized viral trans-activating proteins. The data suggest that the c-myc protein can both stimulate and inhibit transcription from mammalian promoters in a novel manner.

Animals↗

Multiple basal elements of a human hsp70 promoter function differently in human and rodent cell lines.

The human heat shock protein 70 (hsp70) gene is expressed constitutively in a wide variety of cells. Two separate promoter domains determine this basal level of hsp70 expression. The proximal domain is contained within 84 bases of the transcription initiation site and consists of three elements which appear to interact with the TATA factor(s) and CCAAT-box-binding transcription factor and SP1, respectively. The proximal domain is sufficient for near-maximal basal expression to rodent cell lines. The distal promoter domain consists of sequences upstream of -84 and is necessary in conjunction with the proximal domain for full basal expression in human cell lines. Although in BALB/c 3T3 cells the distal promoter domain plays little role in basal expression, it is functional as evidenced by the ability to compensate efficiently for mutations in the proximal CCAATC homology. The distal domain does not compensate as efficiently for proximal-domain mutations in HeLa cells. Basal expression of this human hsp70 promoter is, therefore, determined by multiple elements. Fewer elements are required for basal expression in rodent cell lines than in human cell lines, suggesting that there are significant differences between the rodent and human transcription apparatuses.

Animals↗

Cryptic branch point activation allows accurate in vitro splicing of human beta-globin intron mutants.

The excised introns of pre-mRNAs and intron-containing splicing intermediates are in a lariat configuration in which the 5' end of the intron is linked by a 2'-5' phosphodiester bond (RNA branch) to a single adenosine residue near the 3' end of the intron. To determine the role of the specific sequence surrounding the RNA branch, we have mutated the branch point sequence of the human beta-globin IVS1. Pre-mRNAs lacking the authentic branch point sequence are accurately spliced in vitro; processing of the mutant pre-mRNAs generates RNA lariats due to the activation of cryptic branch points within IVS1. The cryptic branch points always occur at adenosine residues, but the sequences surrounding the branched nucleotide vary. Regardless of the type of mutation or the sequences remaining within IVS1, the cryptic branch points are 22 to 37 nucleotides upstream of the 3' splice site. These results suggest that RNA branch point selection is primarily based on a mechanism that measures the distance from the 3' splice site.

Adenosine↗

Distribution of membrane cholesterol of adrenal cortical cells after corticotropin stimulation.

Membrane cholesterol in adrenal cortical cells is enriched in the plasma membrane. Stimulation of isolated adrenal cortical cells with corticotropin leads to the production of corticosterone. At high levels of corticotropin, cholesterol for corticosterone synthesis arises by hydrolysis of cellular cholesteryl ester, whereas at lower levels of corticotropin cholesteryl ester levels are unchanged from control values and there is a decrease in plasma-membrane cholesterol levels.

Adrenal Cortex↗

Measles virus panniculitis subsequent to vaccine administration.

A severe illness developed gradually in a healthy boy following administration of live measles vaccine at age 14 years. Killed measles vaccine had been given at age 2. Panniculitis began near the site of live vaccine injection, extended contiguously to involve the entire upper arm, and then began to appear in distant subcutaneous sites. He was febrile, leukopenic, anemic, and lost weight rapidly. Evidence of a cause-and-effect relationship between the lesions and the measles vaccine included biopsy findings of particles closely resembling measles nucleocapsids and complete virions by electron microscopy, positive fluorescence after staining with two anti-measles nucleocapsid sera, and immunologic aberrations. The lesions regressed after various treatments and completely remitted on two occasions, but recurred. He became severely malnourished and finally died 29 months after the measles vaccination. At autopsy, pannicultitis was found in the subcutis and mesentery, without evidence of involvement of the brain or other vital organs.

Adipose Tissue↗

Cephalosporanic acids: a new look at reactions at the C-3' position.

Nucleophilic displacement of the acetoxy group of cephalosporanic acids by thiols in aqueous solution at neutral pH provides 3-thiomethyl-substituted compounds with a broad spectrum of antibiotic activity. The aqueous displacement reaction is often destructive of much of the cephalosporanic acid, and products generally require extensive purification. Displacements at a lower pH are complicated by unwanted lactone formation. However, reactions conducted under acid conditions in a variety of anhydrous organic solvents give 3-thiomethyl-substituted compounds in very high yield and quality; no lactone formation is observed. The kinetics of the reaction support an SN1 mechanism. Protonation of the departing acetoxy group appears therefore critical; the more basic solvents, e.g. dimethylsulphoxide and N,N-dimethylformamide, significantly retard the rate of reaction.

Acids↗

Amniotic fluid phosphatidylglycerol in diabetic pregnancies.

Despite L/S ratios indicating fetal lung maturity, respiratory distress continues to occur more frequently in infants of diabetic mothers. Amniotic fluid pulmonary phospholipids were studied in an attempt to understand the occurrence of false-positive L/S ratios in preterm diabetic pregnancies. Qualitative chromatography assays of surfactant phosphatides revealed reduced or absent phosphatidylglycerol in diabetic amniotic fluid specimens between 34 and 37 weeks' gestation. Mean phosphatidylglycerol in 15 nondiabetic and 29 diabetic specimens was 16 and 4 per cent of total extracted pulmonary phospholipids (P less than 0.001). Non-insulin-dependent diabetic pregnancies had lowest mean per cent phosphatidylglycerol. Respiratory distress occurred in six infants of diabetic mothers delivered preterm with L/S ratios of 2:1 or greater; phosphatidylglycerol was absent in five. The inclusion of phosphatidylglycerol in amniotic fluid phospholipid assessment may be an adjunctive index for fetal lung maturation in diabetic pregnancies.

Amniotic Fluid↗

Effect of bacterial endotoxin and inhibitors on tryptophan oxygenase induction in mouse liver slices.

Tryptophan oxygenase activity in mouse liver slices maintained in cluture medium, in Krebs-Ringer bicarbonate solution, or in homologous whole blood declined within 3 hr to about one-half the original level. Actinomycin D and puromycin accelerated the rate of decline, but endotoxin did not. Direct addition of tryptophan to the medium resulted in a higher than normal tryptophan oxygenase activity within 1 hr, and this was maintained well above that of control liver slices up to 6 hr. Triamcinolone, at a dose that doubles tryptophan oxygenase activity in vivo, had no effect on the enzyme in liver slices. Actinomycin and endotoxin did not alter the substrate induction of tryptophan oxygenase; however, puromycin did, but to a limited extent. Liver slices prepared from mice 4 hr after an injection of cortisone had a greater tryptophan oxygenase activity than those of controls. Either endotoxin or actinomycin D resulted in a more rapid decline of the enzyme when added to the slices than was observed in the controls.

Animals↗