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Biomedical subjects

J M Greene

Publications and source records attributed to J M Greene.

At least 37 records · Page 2Linked to original sources
PubMed1995

Antimicrobial characterization and interrelationships of dirithromycin and epidirithromycin.

Dirithromycin is the 9-N,11-O-oxazine adduct formed from 9(S)-erythromycylamine and 2-(2-methoxyethoxy)acetaldehyde in which the methoxyethoxymethyl substituent on the oxazine ring possesses the R configuration. Epidirithromycin is its isomer in which the methoxyethoxymethyl substituent has the opposite (S) configuration. Both compounds readily epimerize in solution, reaching an equilibrium ratio of 85:15 in favor of dirithromycin, given sufficient time. The rate of interconversion is dependent upon pH, temperature, and solvent. An enriched sample of epidirithromycin (95% purity) was synthesized by condensing erythromycylamine and 2-(2-methoxyethoxy)acetaldehyde in diethyl ether as the reaction solvent, and the product was fully characterized by nuclear magnetic resonance spectroscopy and high-pressure liquid chromatographic (HPLC) analysis. Both oxazine derivatives readily hydrolyze to erythromycylamine, so all three compounds exhibit the same antibiotic activity in vitro. In order to determine whether dirithromycin itself possesses significant antimicrobial activity without initial hydrolysis to erythromycylmine, inhibition of cell-free ribosomal protein synthesis was measured under conditions which were adapted to minimize hydrolysis, as measured by analytical HPLC in parallel experiments. Under these particular conditions, inhibition of ribosomal protein synthesis by dirithromycin was < 10% of the value measured for erythromycylamine.

Anti-Bacterial Agents↗
PubMed1994

Autoimmune hemolytic anemia in chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis is an immunodeficiency disease characterized by T-cell dysregulation and chronic superficial candidal infections. We report on three patients with chronic mucocutaneous candidiasis who developed autoantibodies to erythrocytes. Our first patient, a 19-year-old female, developed autoimmune hemolytic anemia (AIHA) that required multiple courses of treatment, including corticosteroids, intravenous immunoglobulin, and danazol. During the last exacerbation of AIHA, intensive treatment with corticosteroids and intravenous immunoglobulin failed and yet the patient responded to plasmapheresis. Our second patient, a 21-year-old male, developed AIHA which responded to oral corticosteroid therapy. Our third patient, a 6-year-old female without evidence of hemolysis, was found to have erythrocyte autoantibodies on routine screening. These three patients had positive direct antiglobulin tests, and the first patient had both immunoglobulin G (IgG) and IgM erythrocyte autoantibodies, while the remaining two patients had only IgG autoantibody. This is the first report of the association of AIHA with chronic mucocutaneous candidiasis. We suggest that all patients with chronic mucocutaneous candidiasis be screened periodically for erythrocyte autoantibodies. Plasmapheresis, a safe ancillary procedure in the management of AIHA, may be life-saving in some cases. The occurrence of erythrocyte autoantibodies in mucocutaneous candidiasis may be related to immunoregulatory disorders in this disease.

Adolescent↗
PubMed1993

Intragastric nitrosation of nicotine is not a significant contributor to nitrosamine exposure.

To determine the potential for intragastric nicotine nitrosation, we carried out a kinetic study of the reaction of nicotine with nitrous acid in aqueous solution. The reaction of nicotine with nitrous acid resulted in the formation of three products, NNA, NNN, and NNK. The three parallel reactions were first order of 10-6 L/mol/s. The optimum pH range for formation of NNA, NNN, and NNK was 2.4 to 3.1. Thiocyanate (100 mM) slightly increased the rate of formation of NNN and NNK but tripled the rate of formation of NNA at pH 3.5 at 37 degrees C. We have also studied the nitrosation of pseudooxynicotine, a bacterial and fungal metabolite of nicotine. This secondary amine nitrosated rapidly to produce NNK. Our proposed mechanism for the conversion of nicotine to NNK includes nine kinetically distinct steps and is in agreement with our experimental results. The rate limiting step involves the formation of nicotine-1',2'-iminium ion. This ion hydrolyzes to form pseudooxynicotine which undergoes rapid, irreversible nitrosation to NNK. Given the very slow rate of nicotine nitrosation, it is unlikely that nicotine itself contributes to exposure to nitroso compounds due to chemically mediated intragastric nitrosation.

Butanones↗
PubMed1993

A novel family of retrotransposon-like elements in Xenopus laevis with a transcript inducible by two growth factors.

A cDNA clone named 1A11 was isolated in a screen for genes that are activated by both mesoderm inducing factors FGF and activin in animal explants of Xenopus laevis embryos. In undisturbed embryos, 1A11 is expressed during the gastrula stage in the entire marginal zone where mesoderm originates, and later in the somites, the tailbud, and at much lower levels in lateral mesoderm. The 1A11 sequence of 4.5 Kb has a 220 bp repeat at its ends, indicative of a retrotransposon-like structure. A long open reading frame encodes a predicted protein with only short homologies to the gag and protease regions of retroviruses and retrotransposons. Multiple copies of 1A11-related sequences were found in the Xenopus genome, constituting solo LTRs (long terminal repeats) of 1267 bp, and unique region copies (i.e., sequences internal to the repeats in the cDNA). Inverted repeats of 5 bp and apparent target site duplications of 5 bp surround the sequenced solo LTR. Thus, 1A11 is a new retrotransposon-like element in Xenopus laevis.

Activins↗
PubMed1993

Outpatient management with oral corticosteroid therapy for obstructive conditions in chronic granulomatous disease.

We report the outpatient management of three patients with X-linked chronic granulomatous disease, two of whom had episodes of gastric outlet obstruction and another, urinary bladder obstruction. These obstructive conditions were successfully treated with 2-week courses of orally administered corticosteroids with or without the addition of orally administered clindamycin. There were no infectious or other adverse reactions.

Administration, Oral↗
PubMed1993

Plasma ascorbic acid concentrations relate inversely to blood pressure in human subjects.

This study relates antioxidant status and blood pressure (BP) in 168 healthy residents of Augusta, GA, following usual diets. BP ranges were systolic (S) 84-152, mean 112 +/- 1 mm Hg, and diastolic (D) 52-96, mean 72 +/- 1 mm Hg. Plasma concentrations of ascorbic acid (AA) were significantly inversely related to SBP (r = -0.18, P < 0.05) and DBP (r = -0.20, P < 0.01); with regression equations SBP vs AA = -0.083C + 116 and DBP = -0.077C + 76. Highest and lowest quintiles of AA differed significantly in mean SBP (108 +/- 2, 113 +/- 2 mm Hg) and DBP (69 +/- 1, 74 +/- 2), P < 0.05. Plasma AA concentrations were significantly lower in the smokers. By deleting smokers, the inverse relations of SBP and DBP with plasma AA and the slopes of the equation were enhanced. Plasma selenium, alpha-tocopherol, alpha-tocopherol:cholesterol ratio, retinol and taurine were not related to BP; whereas male gender, body mass index, body fat distribution, plasma cholesterol, low density lipoprotein cholesterol, and triglycerides correlated.

Adipose Tissue↗
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↗