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Biomedical subjects

S R Brown

Publications and source records attributed to S R Brown.

At least 19 recordsLinked to original sources
PubMed1991

Temporal trends in the incidence of cutaneous malignant melanoma among Caucasians in the San Francisco-Oakland MSA.

Temporal changes in the incidence of cutaneous malignant melanoma (CMM) were examined in the San Francisco-Oakland (California, United States) Metropolitan Statistical Area (MSA) between 1976 and 1987, using data from the population-based cancer registry. This analysis was conducted after the completion of a project designed to eliminate bias in the reporting of CMM due to changes in medical practice. The incidence of CMM is higher in the San Francisco-Oakland MSA than nationally. From 1976 through 1987, the incidence of invasive CMM increased from 9.8 +/- 0.9 to 16.5 +/- 1.1 per 100,000 (P = 0.0001) among men and from 9.3 +/- 0.8 to 12.7 +/- 0.9 per 100,000 (P = 0.001) among women. Age-specific, histologic-specific, and anatomic site-specific trends were also evaluated. The temporal patterns of CMM suggest that the recent increases are not accounted for solely by ascertainment bias due to reporting practices. The observed trends are consistent with early detection efforts and with changes in the prevalence of risk factors.

Bias↗
PubMed1991

Is rectosigmoid response to food modulated by proximal colon stimulation?

Rectosigmoid motor activity and postprandial breath hydrogen levels were monitored in eight healthy males under basal conditions and for 3 1/2 hr after a meal (beefburger and breadroll and ice cream incorporating 20 g lactulose). Within minutes of ingestion there was a significant increase in motility index (P less than 0.05) and also an initial temporary rise in breath hydrogen. A late increase in motor activity occurred in seven of eight subjects 123 +/- 19 min after the meal and was temporally related to the beginning of a second, much larger rise in breath hydrogen (r = 0.99; P less than 0.01). The close association between the timing of the rises in breath hydrogen and rectosigmoid motor activity would support the possibility that the latter may be generated by chemical or mechanical stimulation of the proximal colon.

Adult↗
PubMed1991

Recent trends in the incidence of salivary gland cancer.

Beginning in 1985, a sudden and sustained doubling of salivary gland cancer incidence, among men only, is observed in the San Francisco-Oakland Metropolitan Statistical Area. Registry data are examined to determine the nature of this increase and its possible association with the AIDS epidemic. Changes in patient characteristics are assessed by comparing their distribution among recently diagnosed cases (1985-1988) to an expectation based on population growth and the age-specific incidence among patients diagnosed earlier (1973-1984). Based on the observed patterns, it is unlikely that the temporal increase in these tumours is a direct result of the AIDS epidemic or solely the result of a shift in the prevalence of established risk factors. The increase is predominantly seen in men over the age of 75 at diagnosis (O/E = 2.3, p = 0.02) and is observed among both those with and without a prior cancer (O/E = 2.7, p = 0.02 and O/E = 1.5, p = 0.06, respectively). Radiation for the prior cancer was not associated with increased occurrence. Military exposure is crudely approximated by examining birth cohorts. However, the cohort data do not support a hypothesis of military exposure.

Aged↗
PubMed1991

A novel subgroup of exogenous avian leukosis virus in chickens.

An avian leukosis virus with a wide host range belonging to a new subgroup for chickens was isolated from meat-type chicken lines. The virus, of which HPRS-103 strain is the prototype, was of low oncogenicity in chickens but appeared to behave like an exogenous leukosis virus. Neutralizing antibodies to the virus were found in three of five meat-type chicken lines, but not in seven layer lines. The virus and its Rous sarcoma virus pseudotype did not replicate in, or transform, mammalian cells.

Animals↗
PubMed1991

Bringing the medical library to the office desktop.

This demonstration illustrates LRC Remote Computer Services- a dual operating system, multi-protocol system for delivering medical library services to the medical professional's desktop. A working model draws resources from CD-ROM and magnetic media file services, Novell and AppleTalk network protocol suites and gating, LAN and asynchronous (dial-in) access strategies, commercial applications for MS-DOS and Macintosh workstations and custom user interfaces. The demonstration includes a discussion of issues relevant to the delivery of said services, particularly with respect to maintenance, security, training/support, staffing, software licensing and costs.

CD-ROM↗
PubMed1990

Open access gastroscopy: too much to swallow?

OBJECTIVES: To ascertain the proportion of endoscopic examinations with normal findings in patients referred for gastroscopy through hospital medical staff or directly by their general practitioner and to assess the likely effect of targeting endoscopy in older patients. DESIGN: Retrospective audit of the gastroscopy practice of one consultant from 1986 to 1988 from information recorded on a standard form completed at the time of the examination, which contained details of patients, their endoscopic findings, and mode of referral (open access or clinic). SETTING: One district general hospital. PATIENTS: 1545 Consecutive patients from primary catchment area attending for their first gastroscopy; 454 were referred through the outpatient clinic or by hospital colleagues (clinic group) and 1091 were accepted for endoscopy solely on their general practitioner's clinical diagnosis (open access group). RESULTS: Similar numbers (about 40%) of examinations with normal findings were performed in each group, although in patients aged over 40 the proportion with normal findings was significantly higher in the clinic group (p less than 0.03). Endoscopic evidence of gastro-oesophageal reflux disease, peptic ulceration, and gastroduodenal inflammation was equally common in each group; upper gastrointestinal malignancy, however, was significantly more common in patients referred through hospital doctors (5%, 23/454 v 2%, 22/1091 respectively; p less than 0.005) (although many of these patients had already been extensively investigated). IMPLICATIONS: Open access gastroscopy does not increase the number of unnecessary examinations and should become more widely available. Targeting this service to patients aged over 40 would reduce the number of requests but increase the diagnostic yield.

Adolescent↗
PubMed1990

Effect of coffee on distal colon function.

Ninety nine healthy young volunteers (58 men, 34 women, aged 17-27 years) answered a questionnaire concerning their bowel habit with particular reference to the effects of beverages. Twenty nine per cent (63% women) claimed that coffee induced a desire to defecate. The rectosigmoid motor responses to black, unsweetened coffee were then investigated by multiport manometry in 14 healthy-subjects (12 men, two women, eight of whom claimed coffee caused a desire to defecate (responders). Results revealed an increase in motility index within four minutes after ingestion of both regular and decaffeinated coffee (p less than 0.05) in the eight responders, but not in the six non-responders. The increase in rectosigmoid motility induced by coffee lasted at least 30 minutes. There was no increase in the motility index in any subject after a drink of hot water. These results suggest that drinking coffee can stimulate a motor response of the distal colon in some normal people.

Adolescent↗
PubMed1987

Opioid receptor regulation of the release of norepinephrine in brain.

The ability of opioids to inhibit the release of norepinephrine (NE) from slice preparations of brain has been tested. Slices of brain were preincubated with [3H]NE allowing uptake of the [3H]NE into intraneuronal stores of NE. After rinsing, the tissues were incubated at 37 degrees C in Krebs buffer containing 5mM K+, for estimation of baseline release and then in 20 mM K+ to stimulate release. The [3H]NE released into the incubation medium was increased by blockade of neuronal re-uptake with desipramine and by blockade of alpha 2-adrenoceptors with yohimbine. These agents were used routinely in subsequent incubations. Release was also Ca2+ dependent. Stimulated release of [3H]NE from slices of cortex of the guinea pig and rat was inhibited by the mu opioid receptor agonist, Tyr-D-Ala2-Gly-NMePhe-Gly-ol (DAGO) in a naloxone-reversible manner, although naloxone itself produced a measurable inhibitory effect in the absence of opioid agonist. Stimulated release of [3H]NE from slices of guinea pig cortex was also inhibited by the delta receptor selective peptide, [D-Pen2, D-Pen5] enkephalin (DPDPE), and the kappa receptor selective agent, U50,488H. The inhibitory effect of both agents was reversed by naloxone. In rat cortex, DAGO induced a similar inhibition of release to that seen in guinea pig cortex, but DPDPE and U50,488H were much less effective, producing only weak inhibition even in large doses. Similar results were obtained when effects of opioids on [3H]NE release from hippocampus and cerebellum of the guinea pig and rat were compared. In guinea pig tissues, agonists acting preferentially through mu, delta and kappa receptors were all active in inhibiting stimulated release of [3H]NE, but in hippocampus and cerebellum of the rat, only DAGO inhibited release while DPDPE and U50,488H either had no effect or potentiated the stimulated release. These results suggest that in the rat only mu type opioid receptors mediate an inhibitory regulation of NE release from the cortex, hippocampus and cerebellum terminal projections of locus coeruleus noradrenergic neurons. In the guinea pig, stimulated release of [3H]NE was subject to inhibitory regulation by mu, delta and kappa opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Opioid ligand binding sites in the spinal cord of the guinea-pig.

The properties of opioid binding sites in membranes from the spinal cord of the guinea-pig were analyzed in experiments employing radiolabeled opioid ligands, selective or partially selective for mu, delta and kappa-type binding sites. Incubation was conducted at 37 degrees C in a quasi-physiological modified Krebs medium, containing sodium and magnesium. The types of binding sites were discriminated on the basis of their affinities for [3H-D-Ala2-MePhe4-Gly5-ol]enkephalin ([3H]DAGO), [3H-D-Ala2-D-Leu5]enkephalin, and [3H]ethylketocyclazocine and the relative potencies of the displacing ligands, DAGO, [D-Ser2-Leu5]enkephalyl-Thr and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide methanesulfonate hydrate (U50488H), which are selective for mu, delta and kappa type binding sites respectively. In membranes from whole spinal cord, kappa type sites comprised about 60%, mu about 30% and delta about 10% of the total of mu, delta and kappa binding sites. Binding sites of the mu type were also found in the lumbo-sacral region of guinea-pig spinal cord, in contrast to earlier reports of their absence from this tissue. Morphine showed a better than 500-fold selectivity for mu over kappa sites in spinal cord, while nalbuphine and (-)1-cyclopentyl-5-(1,2,3,4,5,6-hexahydro-8-hydroxy-3,6,11- trimethyl-2,6-methano-3-benzazocin-11-yl)3-pentanone methanesulfonate (WIN 44441-3) showed about a 10-fold selectivity for mu sites. The drug U50488H had about a 150-fold greater affinity for kappa than mu-type binding sites.

Animals↗
PubMed1986

Effects of prior exposure to morphine on the opioid inhibition of the stimulated release of [3H]norepinephrine from guinea pig cortex slices.

The potassium stimulated release of [3H]norepinephrine ([3H]NE) from terminal fields of locus coeruleus projections can be inhibited in a dose-dependent manner by mu and kappa selective opioids. Chronic exposure to morphine for six days decreases the maximum achievable depression by the mu selective agonist Tyr-D-Ala2-Gly-Me(Phe)-Gly-ol (DAGO), but has no effect on the degree of inhibition produced by the kappa selective opioid U50,488H.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Sodium regulation of agonist binding at opioid receptors. I. Effects of sodium replacement on binding at mu- and delta-type receptors in 7315c and NG108-15 cells and cell membranes.

The effects of varying the sodium concentration (at constant ionic strength) on opioid binding at mu- and delta-opioid receptors in 7315c and NG108-15 cells has been examined. The binding of [3H]etorphine to mu-receptors on 7315c cells was increased by replacing the sodium in the incubation medium with potassium or N-methyl-D-glucamine. This effect was shown to be attributable to an increase in affinity, with no change in the maximum number of binding sites, both in cell membrane suspensions and in intact 7315c cells. Replacement of sodium with potassium or N-methyl-D-glucamine in NG108-15 membrane or intact cell suspensions also resulted in an increase in [3H]etorphine binding, but in these cells the effect was associated with an increase in the number of binding sites measurable under these experimental conditions. The effects of sodium on opioid inhibition of adenylate cyclase in membrane preparations from 7315c and NG108-15 cells also differed. Sodium reduced apparent agonist affinity in 7315c membranes. In NG108-15 cell membranes, sodium was essential for the demonstration of opioid inhibition of cyclase activity. Increasing the sodium concentration above 0.5 mM resulted in an increase in the fraction of total enzyme activity inhibited by opioid, but the opioid IC50 did not change. In the companion paper, it is shown that the effects of sodium removal on mu- and delta-receptor binding in guinea pig brain neural membranes were similar to those observed in the cell preparations. An increase in intracellular sodium concentration without change in extracellular concentration was effected by incubation of 7315c and NG108-15 cells with the sodium-selective ionophore, monensin. When sodium was present in the extracellular medium, monensin reduced [3H]etorphine binding by 50% or more, both at mu-receptors in 7315c cells and at delta-receptors in NG108-15 cells. In the absence of sodium, however, monensin treatment produced only a small inhibition of binding. These results suggest that sodium acts at an intracellular site to regulate opioid agonist binding at both mu- and delta-receptors, but that the mode of regulation is not identical at each site. Since a reduction in intracellular sodium concentration by removal of extracellular sodium increases agonist binding, and an increase in intracellular sodium following monensin treatment reduces agonist binding, it is probable that the intracellular sodium concentration is a critical regulator of opioid agonist binding in intact cells.

Adenylyl Cyclase Inhibitors↗
PubMed1986

Sodium regulation of agonist binding at opioid receptors. II. Effects of sodium replacement on opioid binding in guinea pig cortical membranes.

We have examined the effects of sodium on the binding of opioid agonists to mu-, delta-, and kappa-receptors in guinea pig cortical membranes. Concentration curves for sodium indicated that maximal inhibition of mu binding by this cation was about 60% and maximal inhibition for delta binding was about 70%, whereas that for kappa binding was only about 20%. The concentration of sodium required for half-maximal inhibition of binding to all three sites was about 10-30 mM, corresponding to the intracellular sodium concentration. The nature of the sodium effect was further characterized by saturation analysis of binding to each of the three receptor types by comparing results obtained in the presence of 120 mM sodium with those obtained with equimolar replacement of sodium by another cation. Two radiolabeled agonists with different structural characteristics were tested for each binding site. In the presence of sodium, the affinity of the labeled agonists for mu sites was approximately 2-3-fold less than in its absence, but the density of binding sites was not changed. At kappa sites, sodium reduced agonist affinity slightly but, again, did not alter the number of binding sites. In contrast, sodium reduced the apparent density of delta-binding sites while leaving the agonist affinity unchanged. Competition against antagonist binding to delta sites indicated that, in the presence of sodium, a higher proportion of sites was in a lower affinity state, as reflected by the biphasic nature of the agonist displacement curve. In contrast, the effect of sodium on displacement of antagonist from mu sites was to of sodium on displacement of antagonist from mu sites was to lower the affinity of the agonist. Competition against antagonist binding to kappa sites also showed a reduction in agonist affinity by sodium, but no change in number of receptors. The results indicate that sodium may differentially regulate agonist binding to opioid receptor types and that this regulation may occur at an intracellular site. The kappa site appears to be less sensitive to sodium than the mu and delta sites.

Animals↗
PubMed1985

Opioid binding to rat and guinea-pig neural membranes in the presence of physiological cations at 37 degrees C.

We have identified mu, delta and kappa opioid binding sites in four types of neural membranes under conditions which include physiological concentrations of ions and an incubation temperature of 37 degrees C. We hypothesize that binding parameters determined under these conditions should be more directly comparable with physiological experiments than parameters obtained under conditions of low ionic concentration and at low temperature. By using either a radioligand which is selective for a single type of opioid binding site or a relatively nonselective radioligand in the presence of an unlabeled selective ligand, we have isolated binding to single populations of sites. Saturation and displacement data were analyzed with the aid of a computerized nonlinear curve fitting program. [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol bound to a single population of sites with the characteristics of mu receptors, as determined by saturation and displacement analysis. Binding to the mu site represented 70% of the total specific opioid binding in rat brain, but only 20 to 30% in guinea-pig tissues. [3H][D-Ala2-D-Leu5]enkephalin bound almost equally well to mu and delta sites, but the delta site could be examined by the inclusion of unlabeled Tyr-D-Ala-Gly-(Me)Phe-Gly-ol in the incubations. [3H]Ethylketocyclazocine bound mu and kappa sites, and Tyr-D-Ala-Gly-(Me)Phe-Gly-ol was also used to block the mu component in experiments in which we studied kappa binding. Binding to kappa sites represented 50 to 60% of the total in guinea-pig tissues, but less than 20% in rat brain.

Animals↗