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Biomedical subjects

J D Brown

Publications and source records attributed to J D Brown.

At least 19 recordsLinked to original sources
PubMed1992

Intravitreal sustained-release ganciclovir.

Current treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome involves frequent intravenous administration of sodium ganciclovir that often results in unacceptable side effects. We have developed devices that release ganciclovir at rates of 2 micrograms/h and 5 micrograms/h in vitro. When implanted into the vitreous of rabbit eyes, mean intravitreal ganciclovir levels of 9 mg/L and 16 mg/L were maintained for more than 80 and 42 days, respectively. Devices were well tolerated, with no toxic effects attributable to the polymers used in the devices. This investigation indicates that these devices can maintain therapeutic levels of drug for extended periods and are well tolerated in the rabbit eye. They may prove useful in the clinical management of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

Animals↗
PubMed1992

Roles of PRP8 protein in the assembly of splicing complexes.

Three different approaches have been used to investigate the roles of the yeast U5 snRNP protein PRP8 in spliceosome assembly: genetic depletion of PRP8 protein in vivo, heat inactivation of temperature-sensitive prp8 protein in protoplasts and inhibition of PRP8 function with antibodies in vitro. In each case, U5 and U4/U6 snRNPs failed to assemble into the forming spliceosomes. In addition, extract prepared from PRP8-depleted cells and extract containing inactivated PRP8 protein had substantially reduced amounts of U4/U6.U5 triple snRNP complexes. Thus, functional PRP8 protein is required for the stable formation of U4/U6.U5 complexes without which spliceosomes fail to form. As spliceosome formation was also blocked by anti-PRP8 antibodies that apparently do not disrupt triple snRNPs, PRP8 protein may play a separate role in the assembly of triple snRNPs into spliceosomes. As a consequence of PRP8 depletion the levels of the U4, U5 and U6 snRNAs declined dramatically. We discuss this in the context of the known genetic interactions between PRP8 and putative RNA helicase (DEAD box protein) genes and propose that PRP8 protein plays a role in regulating dynamic RNA-RNA interactions in spliceosome assembly, possibly ensuring the correct directionality of these events.

Base Sequence↗
PubMed1992

The genetics of nuclear pre-mRNA splicing: a complex story.

The occurrence of introns in nuclear precursor RNAs (pre-mRNAs) is widespread in eukaryotes, and the splicing process that removes them is basically the same in yeasts as it is in higher eukaryotes. Splicing takes place in a very large, multi-component complex, the splicesome, and biochemical studies have been complicated by the large number of splicing factors involved. This review describes how genetic approaches used to study RNA splicing in Saccharomyces cerevisiae have complemented the biochemical studies and led to rapid advances in the field.

RNA Precursors↗
PubMed1992

Intravitreal ganciclovir pharmacokinetics in rabbits and man.

Cytomegalovirus (CMV) retinitis occurs in immunocompromised patients and can be treated by repeated intravenous or intravitreal injections of ganciclovir (GCV) or foscarnet. Due to toxicity and complications these modalities are not ideal. The development of alternative administration routes is hindered by a lack of pharmacokinetic data. Devices giving pseudo zero order release of GCV were implanted intravitreally first in rabbits and then in patients with AIDS associated CMV retinitis as part of a Phase I clinical trial. Steady state intravitreal GCV levels were obtained immediately after death and the elimination rate constants were calculated assuming first order pharmacokinetics. Normalizing for retinal surface area, distribution volume and anatomic volume, the retinal elimination rate constants were calculated. These were found to be 0.017 cm-2hr-1 in rabbits and 0.015 cm-2hr-1 in man. This indicates that the rabbit eye is a good model for studying intravitreal pharmacokinetics of ganciclovir and suggests a common elimination mechanism which may be trans-retinal.

Animals↗
PubMed1992

Elevated short chain fatty acid concentrations in anaerobic small bowel contamination.

Viable bacteria were identified and counted, and short chain fatty acid concentrations measured in small intestinal fluid from 74 fasting children. In nine children with anaerobic small bowel contamination, individual and total short chain fatty acid concentrations were significantly higher than the remainder of the group (p less than 0.01). Using 100 mumol/l as the upper reference limit for total short chain fatty acid concentration, the sensitivity and specificity as a test for anaerobic small bowel contamination was 89% and 98%, respectively. Measuring luminal short chain fatty acid concentrations in proximal small intestinal fluid is an accurate method for detecting anaerobic small bowel contamination in children.

Adolescent↗
PubMed1992

Subconjunctival sustained release 5-fluorouracil.

The authors have developed a sustained release device for 5-fluorouracil (5-FU) made up of a 12 mg pellet of drug coated in a mixture of permeable and impermeable polymers. When implanted subconjunctivally in rabbits, these devices released 5-FU at approximately 1 mg/d for over 10 days. Devices were implanted into four cynomolgus monkey eyes after posterior lip sclerotomy. One eye (treatment) received a device that contained 12 mg 5-FU and the other eye (control) received a placebo device that contained no drug. In control eyes, intraocular pressures returned to normal within 1 wk. In treatment eyes, pressures remained significantly lower throughout the experimental period (3 mo). There was no indication of impaired wound healing, corneal toxicity, inflammation, or damage to the ciliary body in rabbits or monkeys.

Animals↗
PubMed1991

Efficacy trial of a parenteral gonococcal pilus vaccine in men.

A randomized, placebo-controlled, double-blind efficacy trial of a purified gonococcal pilus vaccine composed of a single pilus type was tested in 3123 men and 127 women volunteers. Either 100 micrograms of vaccine or a placebo was given intradermally on day 1 and day 14. Each group was evenly matched with respect to age, sex, prior history of a sexually transmitted disease, sexual exposure during the study and attrition from the study. None of the women volunteers acquired gonorrhoea during the trial. In the male volunteers, 108 vaccine and 102 placebo recipients acquired gonorrhoea 15 days or later after the initial immunization. Vaccines developed a sustained ELISA antibody response to homologous and heterologous pili, but the latter titres were approximately 40% as high as the homologous pilus antibody rises. There were, however, no increases in inhibition of attachment antibody (IEA) titres. Local antibodies (semen) against homologous and heterologous strains were also elicited (ELISA). The vaccine was safe and did not alter the clinical expression of disease. This gonococcal pilus vaccine composed of a single pilus type failed to protect men against gonococcal urethritis.

Adult↗
PubMed1991

Group therapy in a forensic setting.

Mentally ill offenders are especially difficult patients to rehabilitate. Although group therapy is a universal method of treating these patients, their ability to benefit from group therapy has not been proven. The authors studied a group of patients held on Warrants of the Lieutenant Governor to assess their personality characteristics and their ability to develop group dynamics which are beneficial in other patient populations. The findings were that forensic patients have personality characteristics which preclude the development of these therapeutic dynamics.

Activities of Daily Living↗
PubMed1991

Television viewing and adolescents' sexual behavior.

Over the past two decades the sexual content on television has increased in frequency and explicitness but has seldom included depiction of the use of contraceptives. Concurrently, the age of initiation of heterosexual intercourse has decreased and the number of teenaged pregnancies has remained high. Are these trends related? This survey of 391 adolescents found that those who chose heavier diets of sexy television shows were more likely than those who viewed a smaller proportion of sexual content on television to have had sexual intercourse. This relationship held regardless of perceived peer encouragement to engage in sex and across race and gender groups. While causal direction is not clear from these data, the relationship suggests that either sexual activity results in increased interest in sexual content in the media and/or that viewing such content leads to sexual activity. In either case, the finding points to the need for further research and increased discussion and portrayal of the use of contraceptives on television.

Adolescent↗
PubMed1979

High resolution microchemical analysis using soft X-ray lithographic techniques.

High resolution x-ray lithographic studies of cells from chick embryo hearts dried by the CO2 critical point method have been made with soft x-ray radiation of different wavelengths. A marked difference in the relief replica in polymethyl methacrylate (PMMA) resulting from the differential absorption by the dried cells of carbon K alpha radiation at 4.48 nm and broad band synchrotron radiation (SR) with lambda is greater than 1.5 nm demonstrates the potential usefulness of the technique in making high resolution (approximately or equal to 10 nm) chemical identification of the constitutents which make up the various parts of the cell.

Animals↗
PubMed1978

Pituitary pigmentary hormones. Relationship of melanocyte-stimulating hormone to lipotropic hormone.

Pituitary control of pigmentation has known for more than 60 years. Since 1969, beta-melanocyte-stimulating hormone (beta-MSH) has been accepted as the main pituitary pigmentary hormone in man. Its "constant companionship" with adrenocorticotrophic hormone (ACTH) has also been repeatedly demonstrated. Current investigations challenge both of these concepts. Human beta-MSH immunoreactivity has been shown to be actually due to beta-lipotropic hormone (beta-LPH), a larger molecule that within itself contains the entire amino acid sequence of beta-MSH. Human beta-MSH does not exist in vivo; it is merely an extraction artifact formed by enzymatic degradation of beta-LPH. It would appear likely that beta-LPH, not beta-MSH, is the constant companion of ACTH.

Adrenocorticotropic Hormone↗