PubMed Health⌕ Search

Biomedical subjects

J M Greene

Publications and source records attributed to J M Greene.

At least 19 recordsLinked to original sources
PubMed1992

Immunosuppression induced by attenuated Salmonella: effect of LPS responsiveness on development of suppression.

A live, avirulent strain of Salmonella typhimurium, SL3235, was previously shown to afford protection against virulent Salmonella challenge in three mouse strains of the C3H lineage, C3H/HeJ, C3HeB/FeJ, and C3H/HeNCrlBR, which differ in their innate susceptibility to Salmonella infection, as well as in their responsiveness to lipopolysaccharide (LPS). Concurrent with protection, however, SL3235 was found to induce greater than 90% reduction in proliferative responses of splenocytes from immunized mice to a panel of B and T cell mitogens. Suppression appeared to be independent of susceptibility to Salmonella infection, since the mitogenic responses of hypersusceptible C3H/HeJ and C3HeB/FeJ, as well as resistant C3H/HeNCrlBR mice, were suppressed. The suppressor cell population in immunized C3HeB/FeJ mice was recently shown to be of monocytic lineage. Using transwell plates, co-culture studies indicated that suppression was mediated by soluble factors. In the present study, the effect of LPS responsiveness on susceptibility to SL3235-induced suppression was evaluated in C3H mice by studying their ability to mount plaque-forming cell (PFC) responses to sheep red blood cells (SRBC) and in vivo antibody responses to tetanus toxoid. Comparison of PFC responses as a function of SL3235 dose in C3HeB/FeJ and C3H/HeJ mice, revealed that the latter strain was markedly more resistant to the development of suppression, as evidenced by the significantly higher (10-35-fold) SL3235 doses needed to achieve comparable suppression to those seen in C3HeB/FeJ mice. In contrast to C3HeB/FeJ mice, suppression in C3H/HeJ mice required direct cell-cell contact. In both mouse strains, suppression was alleviated by pre-treatment of immune splenocytes with either mitomycin C or x-irradiation, indicating that actively proliferating cells are required for suppressor function. Resistance of C3H/HeJ mice to SL3235-induced suppression was not due to a lesser bacterial load in vivo, since a higher number of SL3235 organisms were seen in C3H/HeJ spleens compared to C3HeB/FeJ mice. Rather, resistance of C3H/HeJ mice correlated with their reduced ability to recruit macrophages and other inflammatory cells into the spleen, as evidenced by the significantly smaller degree of splenomegaly induced in these mice following immunization with SL3235.

Animals↗
PubMed1992

Vitamin A in hypercholesterolemia.

This study evaluated the relationship between plasma vitamin A and cholesterol in 48 patients with hypercholesterolemia studied before and after treatment with a cholesterol-lowering diet, with or without lipid-lowering medication. Plasma vitamin A levels were higher in hypercholesterolemic subjects than in healthy controls (2.58 +/- 0.15 vs. 1.82 +/- 0.14 mmol/L, p = 0.025) despite similar values for retinol binding protein (RBP). Successful cholesterol lowering, defined as greater than 25% reduction in low density lipoprotein cholesterol, was achieved in 16 patients. In this subset, plasma vitamin A declined from 3.00 +/- 0.32 (pretreatment) to 2.34 +/- 0.15 mmol/L (post treatment; p = 0.018). A nonsignificant increase in RBP was observed, resulting in a significant decrease in the molar ratio of vitamin A to RBP (1.05 +/- 0.06 vs. 0.80 +/- 0.05, p = 0.013). These data suggest an interaction between vitamin A and cholesterol that is independent of the transport mechanisms for vitamin A in association with chylomicrons (post absorptive) and with RBP. Further examinations of the form or forms of vitamin A (retinol, retinyl ester), its distribution within the plasma lipoproteins, and the mechanisms of origin and removal are warranted to explain these findings.

Anticholesteremic Agents↗
PubMed1992

Cost-conscious prescribing of nonsteroidal anti-inflammatory drugs for adults with arthritis. A review and suggestions.

Salicylates and nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of painful disorders. This article reviews the efficacy, side effects, and costs of these agents and proposes a practical approach to using them in a cost-effective manner. Although there may be some differences in efficacy among available drugs, these do not appear sufficient to justify using the more expensive agents in most cases. Adverse effects, especially gastrointestinal (GI), add to the cost of using these drugs. Aspirin and all nonsalicylate NSAIDs share a risk of causing gastric ulcer, upper GI bleeding, and GI perforation. Prostaglandin inhibition by these agents may lead to reduced glomerular filtration rate and renal failure. There may be modest differences in GI and renal risks with the different agents, but these are minimal. Prophylaxis against gastric ulceration with anti-ulcer drugs has been recommended, and one agent, misoprostol, is approved for use in the United States for this purpose. Whether use of prophylaxis will increase or decrease the costs associated with NSAID therapy remains to be determined. Nonacetylated salicylates may cause less GI adverse effects and may be somewhat "renal sparing." Strategies that would reduce the cost of care for painful musculoskeletal disorders without compromising quality of care include using acetaminophen instead of an NSAID for noninflammatory disorders, trying nonacetylated salicylates as less expensive and safer alternatives to NSAIDs, using one agent at a time, allowing sufficient time to evaluate the therapeutic effect before changing agents, returning to the least expensive and/or safest drug if a trial of several in succession fails to find one that is clearly better, and reserving prophylactic use of antiulcer agents for patients who are at especially high risk and for whom anti-inflammatory effects are clearly needed.

Adult↗
PubMed1992

Physician's and dietitian's role in obese care.

In the Surgeon General's Report on Nutrition and Health, of the ten leading causes of death in the United States, five are nutrition related. Instead of nutritional deficiencies as seen in the 1940s, the national diet has shifted to dietary excesses and imbalances. Dietary excesses and imbalances are reflected in obesity, a major health problem affecting approximately 30% of the United States' population. Unfortunately, the diet industry is not regulated and, hence, patients have many avenues from which to choose. Many of these leave patients lost and confused as to why they have failed in maintaining their weight loss. It is well documented that the recidivism rate in the obese is high with only 5% maintaining their weight loss after one year. The following is a review of the physician's and dietitian's roles in long-term weight maintenance.

Dietetics↗
PubMed1991

Retrospective analysis of the incidence of pulmonary disease in hypogammaglobulinemia.

To determine the best predictors of chronic pulmonary disease in patients with hypogammaglobulinemia, we evaluated the clinical records, chest x-ray films, and pulmonary function tests of 10 patients with X-linked agammaglobulinemia (XLA) followed for a mean of 12.5 years, and 12 patients with common variable immunodeficiency (CVID) followed for a mean of 10.5 years. These patients, most of whom were treated with intramuscular gamma globulin and long-term oral antibiotics, had very few pneumonias after diagnosis. The patients with XLA had 0.10 pneumonias per treatment year, and the patients with CVID had 0.18 pneumonias per treatment year. Seven of the 10 patients with XLA had normal chest x-ray films 8 to 15 years after diagnosis, and none had bronchiectasis. Pulmonary disease was more common and more severe in the group with CVID, but five patients in this group also had normal chest x-ray films after long follow-up. In the entire group of 22 patients, nine of the 10 patients with abnormal chest x-ray films on most recent evaluation already had pulmonary disease at the initial visit (p = 0.00002). These studies indicate that the best predictors of good pulmonary function in patients with hypogammaglobulinemia are early diagnosis and good compliance with gamma globulin replacement therapy and oral antibiotics.

Agammaglobulinemia↗
PubMed1991

Physician's office guide to a lipid-lowering diet.

To properly treat patients with hyperlipidemia, the physician should have a general knowledge of lipid-lowering diets. The basic principles of these diets, as well as practical application, are discussed.

Behavior Therapy↗
PubMed1991

Synthesis and antimicrobial evaluation of dirithromycin (AS-E 136; LY237216), a new macrolide antibiotic derived from erythromycin.

Dirithromycin is a 9-N-11-O-oxazine derivative which is formed by condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)acetaldehyde. Dirithromycin is hydrolyzed, either under acidic conditions or in vivo, to its major active metabolite, 9(S)-erythromycylamine. The antimicrobial spectrum of dirithromycin is similar to that of erythromycin; both antibiotics are active against gram-positive bacteria, Legionella spp., Helicobacter pylori, and Chlamydia trachomatis. Comparable results were obtained for each antibiotic in MIC and MBC determinations and in the potential development of resistance in vitro. The effects of human serum, bacterial growth media, test methodology, and inoculum size on MICs were similar for each antibiotic. In standard mouse protection studies, dirithromycin was more efficacious than erythromycin against experimental infections after subcutaneous administration of antibiotic. These results were consistent with pharmacokinetic studies in rodents, which showed that dirithromycin gave more persistent concentrations of antibiotic in serum and tissues than were achieved with erythromycin. These studies indicate that dirithromycin possesses antimicrobial activity comparable to that of erythromycin in vitro but is more active than erythromycin in vivo, which may be attributable to the persistence of antimicrobial activity in the tissue(s) of the test animals.

Animals↗
PubMed1990

Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine.

A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine.

Alkylation↗
PubMed1990

TATA-dependent and TATA-independent function of the basal and heat shock elements of a human hsp70 promoter.

We have characterized the interactions between the TATA element and other sequence elements of a human heat shock protein 70 (hsp70) promoter by a mutational approach. Expression of a distal element of this promoter requires an intact TATA element in human cell lines. The hsp70 TATA element can be functionally replaced for this interaction by TATA elements from the simian virus 40 early and adenovirus EIIa promoters. The TATA element in this promoter therefore both determines the appropriate start site and determines strength by allowing function of the distal element. In contrast, three proximal upstream elements necessary for basal and heat-regulated transcription have no requirement either for a TATA element or for any other proximal element. The behavior of promoters multiply mutant in these proximal elements implies that these elements function independently. We examined the interaction between the heat shock element (HSE) and the TATA element as the distance between the two factor-binding sites was increased. It was necessary to create a mutant HSE with an extended consensus sequence in order for the HSE to function at a distance. Moving this extended HSE 500 bases upstream did not increase its dependence on the TATA element, suggesting that the TATA independence of this element is intrinsic to its function and is not determined by distance from the promoter.

Animals↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1985

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↗
PubMed1983

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↗
PubMed1980

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↗