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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 487 records · Page 27Linked to original sources
PubMed1992

Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen.

To characterize the autoantigen of Goodpasture's (anti-glomerular basement membrane) disease, a molecule of 26-kD reactive with autoantibodies from patients' sera was purified from collagenase digests of sheep glomerular basement membrane. Short internal amino acid sequences were obtained after tryptic or cyanogen bromide cleavage, and used to deduce redundant oligonucleotides for use in the polymerase chain reaction on cDNA derived from sheep renal cortex. Molecules of 175 bp were amplified and found to come from two cDNA sequences. One was identical to that of a type IV collagen chain (alpha 5) cloned from human placenta and shown to be expressed in human kidney. The other was from a type IV collagen chain with close similarities to alpha 1 and alpha 5 chains, and was used to obtain human cDNA sequences by cDNA library screening and by further polymerase chain reaction amplifications. The correspondence of the derived amino acid sequence of the new chain with published protein and cDNA sequences shows it to be the alpha 3 chain of type IV collagen. Its gene, COL4A3, maps to 2q36-2q37. The primary sequence and other characteristics of this chain confirm that it carries the Goodpasture antigen.

Amino Acid Sequence↗
PubMed1992

Preparation and characterization of diaspirin cross-linked hemoglobin solutions for preclinical studies.

During 1990 and 1991 the capability for repetitive, consecutive production of DCLHb solution to meet a rigorous and complete set of product criteria was demonstrated. In addition, through periodic monitoring of product stored under controlled conditions, the stability of all lots of DCLHb solution during frozen storage was demonstrated for more than a year. In this way, assurance was provided that the DCLHb solution used in preclinical testing met all product criteria throughout the biological testing period.

Aspirin↗
PubMed1992

How the elderly fare in HMOs: outcomes from the Medicare competition demonstrations.

Because of concern about the effects of prepaid care on outcomes for elderly enrollees in health maintenance organizations (HMOs), a prospective study of access to care and functional outcomes was performed. HMOs with Medicare risk contracts in January 1985 (N = 17) were selected from ten communities and were matched for comparison with ten similar communities where no Medicare HMOs were in operation. Random samples of HMO enrollees (N = 2,098) and fee-for-service (FFS) nonenrollees (N = 1,059) were assessed at baseline and at follow-up one year later (HMO = 1,873, FFS = 916) to observe access to care and functional outcomes. At baseline, nonenrollees had more bed days and poorer functional status than HMO enrollees. While fewer HMO enrollees experienced declines in functional status between baseline and follow-up (e.g., patient's ability to function declined in one or more activities of daily living: HMOs at 5.3 percent versus FFS at 8.5 percent, p < .01), after controlling for other factors with logistic regression, enrollment status was not significantly associated with functional decline. Self-rated health, history of hospitalization, age of 80 or older and baseline functional status were predictive of decline in function. After controlling for baseline differences, HMO disenrollees also experienced similar functional declines at follow-up compared to continuously enrolled beneficiaries. These findings suggest that Medicare beneficiaries who belong to HMOs experience comparable rates of functional decline to those experienced by beneficiaries in the FFS sector with similar initial levels of function and health status. Together with results showing no significant difference in medical visits according to various symptoms, we conclude that access and quality of care delivered by HMOs is comparable to that provided in FFS settings.

Activities of Daily Living↗
PubMed1992

MailMinder: taming DHCP's mailman interface.

While the Department of Veteran's Affairs Decentralized Hospital Computer Program (DHCP) is one of the most widely disseminated and successful hospital information systems in existence, it currently is accessed through a user interface which is not as mature as the rest of the system. This interface is a VT-100 compatible, character oriented interface using menus accessed by typed commands for feature access. This project demonstrated that a mature graphical user interface (MailMinder) can be successfully used as a "front-end" to DHCP. MailMinder is completely compatible with the existing unmodified DHCP electronic mail program, Mailman. MailMinder allows the user to be more efficient than the current interface and offers additional features over the current mail system. The program has undergone evaluation and limited deployment at five separate sites. The feature set of this program and its operation will be shown at this demonstration. The demonstration has implications for all current hospital information systems.

Computer Graphics↗
PubMed1992

The relaxant properties in guinea pig airways of S-nitrosothiols.

Several cellular constituents of the lung have the capacity to synthesize a factor capable of relaxing smooth muscle which has the physicochemical properties of nitric oxide (NO). In other systems, it has been shown that NO may be stabilized in the plasma and cellular milieu by reduced thiol in the form of an S-nitrosothiol (RS-NO). These compounds have half-lives that are significantly greater than that of NO, and also retain the vasorelaxant activity of NO, which is mediated by activating guanylate cyclase and raising cyclic GMP levels. The effects of RS-NO and their potential mechanism of action on airways, however, have not been previously investigated. In this study, we have examined the smooth muscle relaxant properties of several biological and synthetic RS-NO on guinea pig trachea. Our data reveal that RS-NO are generally potent airway smooth muscle relaxants with at least a partial effect through stimulation of cyclic GMP. Relaxations were attenuated significantly by the guanylate cyclase inhibitor methylene blue (P less than .05), and RS-NO-induced increases in cyclic GMP were demonstrated (P less than .0005). The IC50 values for S-nitroso-glutathione, S-nitroso-cysteine, S-nitroso-homocysteine, S-nitroso-N-acetylcysteine, S-nitroso-penicillamine and S-nitroso-captopril were 0.99 +/- 0.09, 3.2 +/- 0.2, 2.1 +/- 0.3, 2.1 +/- 0.8, 1.8 +/- 0.8 and 20 +/- 0.7 microM (mean +/- S.E.M.), respectively. In this system isoproterenol has an IC50 of 0.016 microM and theophylline an IC50 of 74 microM, making the relaxant properties of these NO derivatives of potential pharmacological and physiological relevance.

Animals↗
PubMed1992

Self-evaluations and intergroup attitudes in children aged three to nine.

The effects of individual and group performance on children's evaluations of themselves and in- and out-group were examined. 128 girls and boys aged 3, 5, 7, and 9 years were randomly assigned to alleged "fast" or "slow" teams and asked to make various self, interpersonal, and intergroup evaluations. These showed strong developmental changes. Intergroup comparisons were made as early as 3 years, and this age group was sensitive to the relative standing of their team. However, the 5-year-old children showed markedly high self-evaluations, very strong in group bias in their evaluations of the 2 teams, and a high level of group cohesion irrespective of their own team's alleged performance. Gender differences were observed in self-evaluations after team assignment (boys responding more than girls to their team's alleged performance). The implications of these findings for recent work based on cognitive-developmental and social identity theories are discussed.

Attitude↗
PubMed1992

An integrated approach to rehabilitation engineering education: the development of a new masters programme at Brunel University.

We report on a new multidisciplinary course at Master's Level; a joint venture between the Department of Design at Brunel University. U.K. and Brunel Institute for Bioengineering. The Bachelor of Science degree in Industrial Design at Brunel includes an important proportion of technological courses such as mechanics and electronics. The MSc course, which is modular, continues to embrace a wide range of disciplines but it also seeks to bring together graduates from traditional engineering backgrounds in addition to those from arts based design courses. Appropriate elements are offered in order to allow access into unfamiliar disciplines. One novel and valuable aspect of the course is the way in which graduates from diverse backgrounds, having complementary experience and skills will be studying and developing projects alongside one another. Although much of the academic content will be through the department of Design and the Faculty of Technology, the Brunel Institute for Bioengineering will play a major role in the provision of modules in Rehabilitation Studies and in the generation and supervision of projects. This project work will therefore be carried out within the Rehabilitation Engineering Unit at Brunel Institute for Bioengineering. The course to be discussed has been developed at Brunel University in the department of Design in conjunction with The Brunel institute for Bioengineering.

Curriculum↗
PubMed1991

Single step selection of cis-diamminedichloroplatinum(II) resistant mutants from a human ovarian carcinoma cell line.

We have shown that cis diamminedichloroplatinum-(II) (DDP) resistant mutants can be isolated from the human ovarian carcinoma cell line A2780 using a single-step selection protocol with DDP. DDP resistant colonies were calculated to be present at a frequency of 1.7 x 10(-6)/viable cell using a fluctuation analysis. The mutational origin of these surviving colonies is inferred by the fact that their frequency is increased by treatment of the A2780 cells with the chemical mutagen ethyl methane-sulfonate, with a maximum frequency observed after a 3-day expression time. Independently isolated clones maintain, in the absence of selection, a DDP resistant phenotype up to 7-fold more resistant than the parental A2780 cells. The resistance modifiers aphidicolin and buthionine sulfoximine have no effect on the frequency of DDP resistant mutants. Therefore neither of these drugs appears to have an effect on increasing the sensitivity of DDP resistant mutants existing in a cell population prior to DDP exposure.

Aphidicolin↗
PubMed1991

Molteno implants and operating microscope-induced retinal phototoxicity. A clinicopathologic report.

The right eye of a 75-year-old man with a history of cataract extraction, three penetrating keratoplasties, laser trabeculoplasty, two Molteno implants, and an operating microscope-induced retinal phototoxic lesion was studied post mortem. Histopathologic examination of the anterior segment showed evidence of penetrating keratoplasty, cataract surgery, and two Molteno implants with minimal associated tissue response. Ultrastructural examination showed a loose collagenous matrix surrounding the Molteno reservoirs, suggesting aqueous percolation from the reservoirs into the conjunctiva. Posteriorly, in the area of the phototoxic operating microscope-induced lesion, a nodule of retinal pigment epithelial hyperplasia with overlying atrophy of the photoreceptor cell layer of the neurosensory retina was noted. The retina also contained cystoid macular edema and an extensive preretinal membrane that was clinically unexpected.

Aged↗
PubMed1991

Analytical and micropreparative capillary electrophoresis of the peptides from calcitonin.

The capillary electrophoresis (CE) of peptide fragments from the tryptic digest of salmon calcitonin and elcatonin has been carried out in H2O- and D2O-based buffer solutions. Analysis in heavy water was found to be superior to that in H2O especially at a pH or pD of 7.93. From a single CE run on elcatonin digest we were also able to harvest three pure cleavage peptides in sufficient quantity to determine each amino acid residue by protein sequencing. The order of elution from CE agreed with that predicted on the basis of net charge calculated for each peptide.

Amino Acid Sequence↗
PubMed1991

Suppression of splenic macrophage interleukin-1 secretion following intracerebroventricular injection of interleukin-1 beta: evidence for pituitary-adrenal and sympathetic control.

Intracerebroventricular (ICV) injections of interleukin-1 beta (IL-1 beta) produced a dose-dependent increase in plasma corticosterone and adrenocorticotropic hormone (ACTH) within 2 hr of injection and then declined over the next 24 hr. Using a potent steroidogenic dose of IL-1 beta (5 ng), ICV injection resulted in suppression of splenic macrophage IL-1 secretion following stimulation by LPS in vitro. Macrophage TGF-beta secretion was not affected, indicating a differential action of ICV IL-1 beta on macrophage cytokine production. Following adrenalectomy (ADX), the suppressive effect of ICV IL-1 beta was reversed and resulted in stimulation of macrophage IL-1 secretion, indicating that the suppression was mediated by adrenocorticol activation. However, surgical interruption of the splenic nerve to eliminate autonomic innervation of the spleen also prevented the macrophage suppressive signal in rats given ICV IL-1 beta. Furthermore, the combination of ADX and splenic nerve section resulted in a potent stimulatory effect of ICV IL-1 beta on splenic macrophage IL-1 secretion which was greater than either ADX or splenic nerve section alone. These results support the concept of a negative feedback on macrophage IL-1 secretion by the central action of IL-1 beta and indicate that both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system mediate this effect.

Adrenalectomy↗
PubMed1991

Conditioned taste aversion but not adrenal activity develops to ICV administration of interleukin-1 in rats.

In a previous investigation with mice, the paired presentation of either odor or taste cues with the peripheral (IP) administration of the immunoactive peptide interleukin-1 (IL-1) led to the conditioned enhancement of glucocorticoid production. The present study found that an initial central infusion of IL-1 in the presence of saccharin cues produced a robust taste aversion but not a conditioned elevation of either ACTH or corticosterone production. These results indicate that the glucocorticoid response induced by centrally administered IL-1 in rats is independent of the behaviorally aversive properties of this cytokine which are conditionable. The differential effects of IP versus ICV administration of IL-1 on glucocorticoid conditioning requires a clearer specification of the respective signaling mechanisms and pathways activated by these two routes of administration.

Adrenocorticotropic Hormone↗
PubMed1991

Modulation of body temperature through taste aversion conditioning.

Injection of rats with bacterial lipopolysaccharide (LPS) results in an initial fall in body temperature followed by a fever. Lithium chloride (LiCl) injection induces a fall in body temperature without subsequent fever production. When these substances were incorporated as unconditioned stimuli in a taste aversion conditioning paradigm, using saccharin flavour as the conditioning stimulus, these differential effects on body temperature were reenlisted on reexposure to saccharin alone 7 days after conditioning. The changes in body temperature on reexposure were similar in direction and kinetics as on the conditioning day although reduced in magnitude. The finding of a true conditioned effect in these studies is in contrast to the paradoxical or compensatory conditioned body temperature responses described elsewhere using different conditioning models. This apparent conflict may be explained on the basis of different unconditioned stimuli acting on efferent versus afferent arms of a negative feedback system. Since body temperature changes often occur in association with immune responses, these findings may have implications to behavioural conditioning of immunity, the outcome of which may reflect the indirect effects on immunity of inadvertent conditioning of thermoregulatory changes.

Animals↗
PubMed1991

The effect on minimum tumor dose of restricting target-dose inhomogeneity in optimized three-dimensional treatment of lung cancer.

An examination was made of the effect upon the minimum tumor dose of a limit placed on the variation of dose across target. If the required level of target dose uniformity is slightly relaxed, a substantial improvement in the minimum tumor dose might appear. It was conjectured that this effect could be seen with treatments optimally planned and evaluated in three-dimensions. A model of advanced carcinoma of the lung treated with a computer controlled accelerator was used to test this hypothesis. A mathematical program for optimizing beam weights was used to determine the largest minimum tumor dose possible. In the six cases tested, a minimum tumor dose of greater than 80 Gy could be delivered if a 20% inhomogeneity limit was accepted. The minimum tumor dose fell to the range 44-64 Gy when the inhomogeneity limit was tightened to 13-17%. The results imply a need to examine the choice of a required level of dose uniformity from the range of values suggested in the 2-dimensional planning literature. If a strict bound-on-dose uniformity is preserved, mechanisms--such as formal optimization--which can reduce target dose inhomogeneity will be valuable.

Dose-Response Relationship, Radiation↗