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Biomedical subjects

R J Brown

Publications and source records attributed to R J Brown.

At least 19 recordsLinked to original sources
PubMed1995

Diurnal variation in tardive dyskinesia.

Tardive dyskinesia (TD) is a common movement disorder that is associated with chronic neuroleptic exposure. To better characterize the clinical aspects of TD, we investigated the diurnal pattern of involuntary movements by blindly rating videotaped examinations of patients from the morning shortly after awakening and later in the same afternoon. In 10 patients, average TD ratings were worse in the afternoon than in the morning, especially in the case of limb-trunk dyskinesias. These findings suggest that it is important to rate patients at the same time of day in TD studies. Moreover, patients should be evaluated at least several hours after awakening.

Adult↗
PubMed1995

Structure-activity relationships of new heterocycle-containing bisphosphonates as inhibitors of bone resorption and as inhibitors of growth of Dictyostelium discoideum amoebae.

The mechanisms by which bisphosphonate drugs inhibit osteoclast-mediated bone resorption are unclear. Effects of bisphosphonates on cellular enzymes, metabolic pathways, and osteoclast morphology have previously been described and could culminate in a generalized cytotoxic effect or a decreased capacity of osteoclasts to resorb bone. Recent studies of the structure-activity relationship for the bisphosphonate side chain indicate, however, that at least the newer generations of nitrogen-containing bisphosphonates probably act by binding to a specific target at a site that is complementary in structure to the bisphosphonate side chain. We have previously proposed that such a target for bisphosphonates is also present in amoebae of the cellular slime mold Dictyostelium discoideum, because growth of this microorganism is inhibited by a wide range of bisphosphonates in a manner that closely reflects the antiresorptive potencies of the bisphosphonates in vivo. We have added support for this view by examining the potency towards Dictyostelium of bisphosphonates in which slight changes in the structure of the side chain or conformational restrictions to the side chain have marked effects on antiresorptive potency. The changes in the side chain that affected the in vivo antiresorptive potency of the bisphosphonates consistently affected in a similar manner the potency of the bisphosphonates as inhibitors of the growth of Dictyostelium amoebae. These observations confirm that bisphosphonate drugs have a molecular target that is common to both Dictyostelium amoebae and osteoclasts.

Animals↗
PubMed1992

Proteolytic activity of proteinases on macropeptide isolated from kappa-casein.

Proteolytic activities of chymosin, bovine pepsin, Mucor miehei rennet, Cryphonectria parasitica (formerly Endothia parasitica) rennet, trypsin, and chymotrypsin on kappa-casein macropeptide were measured. Macropeptide solutions (10 mg/ml of .05 M, pH 6.6 phosphate buffer) were incubated with the enzymes at 37 degrees C for various times, and their reactions were stopped by adding .025 ml of pepstatin (1 mg/ml of methanol). Peptides released from kappa-casein macropeptide were then fractionated using reverse-phase HPLC. At the pH of milk (pH 6.6), kappa-casein macropeptide was resistant to enzymic action by chymosin, bovine pepsin, and M. miehei and C. parasitica rennets. Bovine pepsin hydrolyzed kappa-casein macropeptide at pH 3. kappa-Casein macropeptide was readily hydrolyzed at pH 6.6 by trypsin and chymotrypsin. Possible physiological functions of the kappa-casein macropeptide are discussed in light of these findings.

Carbohydrate Sequence↗
PubMed1991

Separation of beta-casein A1, A2, and B using cation-exchange fast protein liquid chromatography.

beta-Casein genetic variants A1, A2, and B were separated using cation-exchange fast protein liquid chromatography. beta-Casein from a herd bulk casein sample eluted as a series of three peaks. Casein samples from individual cows containing known combinations of beta-casein A1, A2, and B were used to confirm that the three peaks were beta-casein genetic variants. An acid-PAGE gel confirmed the identity of the peaks that eluted from the column.

Animals↗
PubMed1991

Casein interference in bovine plasmin assays using a synthetic substrate.

Bovine plasmin (EC 3.4.21.7) activity on H-D-valyl-L-leucyl-L-lysyl-4-nitroanilide was measured by determining the change in absorbance at 405 nm. Initial rates of reactions were estimated at all combinations of the following substrate concentrations [.4, 4, and 40 times the substrate concentration at one-half maximum velocity (Vmax) (Km)] and casein concentrations [.068, .68, and 6.8 times the inhibitor constant for competitive inhibition (KI)]. By nonlinear least squares fitting of the data to an equation that described reversible enzyme kinetics, steady state kinetic parameters, maximum velocity (Vmax), substrate concentration at one-half maximum velocity (Vmax) (Km), inhibitor constant for competitive inhibition (KI), and inhibitor constant for uncompetitive inhibition (KI) were estimated. Casein fit the equation as a competitive inhibitor of bovine plasmin. This enzyme has a catalytic constant (Kcat) of .0158 change in absorbance at 405 nm/min per nM, substrate concentration at one-half maximum velocity (Vmax) (Km) of .107 mM substrate, and inhibitor constant for competitive inhibition (KI) of .86 mg/ml of casein. Bovine plasmin activity can be measured directly in bovine milk without interference from casein.

Animals↗
PubMed1987

Explorations of a crisis intervention service.

Descriptive studies of a crisis intervention service replicated previous findings of relationships between staff members' attitudes towards treatment and their 'personal styles'. The attitudes and personal styles of crisis team members and non-members differed, largely because of differences in the professions making up these groups. While all staff groups shared the same concept of crisis, they differed in their discrimination of crisis cases from 'furores'. Initial crisis intervention interviews exhibited more confrontation and less exploration by therapists than did initial psychiatric out-patient clinic interviews. Patients referred to the crisis team differed from significant other people in their lives, and from control patients referred to the ordinary out-patient clinic, in aspects of their perception of problems.

Attitude of Health Personnel↗
PubMed1986

Immobilization-associated osteoporosis in primates.

The progressive osteopenic changes in tibial compact bone in adult male monkeys (Macaca nemestrina) were examined histologically during chronic studies of immobilization. The animals were restrained in a semirecumbent position, which reduces normally occurring stresses in the lower extremities and results in bone mass loss. The longest immobilization studies were of 7 months duration. Losses of haversian bone tended to occur predominantly in the proximal tibia and were characterized by increased activation with excessive depth of penetration of osteoclastic activity. There was no apparent regulation of the size and orientation of resorption cavities. Rapid bone loss seen during 10 weeks of immobilization appeared to be due to unrestrained osteoclastic activity without controls and regulation, which are characteristic of adaptive systems. The general pattern of loss persisted throughout 7 months of immobilization. Clear-cut evidence of a formation phase in haversian bone was seen only after 2 months of reambulation. During this period osteoblasts accumulated within resorption cavities, and there was matrix apposition. Within 6 months of recovery there was increased bone turnover, and resorption cavities with diameters of 500-1500 micron were filled partially with new bone; the mean wall thickness of new bone was 2 to 3 times larger than normal. In addition there were numerous remodeling sites that were of normal size and orientation. Trabecular bone was lost during immobilization, and it is probable that losses of large trabecular plates are not replaced, and consequently original bone volume in the cross section is not recovered. In this immobilization model we observed bone resorption occurring for long periods without apparent interruption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of pH, calcium chloride, and chymosin concentration on coagulation properties of abnormal and normal milk.

Individual Holstein cow milk samples were selected for good and poor chymosin-coagulation characteristics. The effect of pH adjustment, addition of .02% calcium chloride, and variation in chymosin concentration on coagulation properties of good and poor coagulating samples was evaluated. Pooling 50% good and 50% poor coagulating samples did not improve the average coagulation properties of the poor samples. Reducing milk pH to 6.3 caused a significant decrease in coagulation time but a less marked increase in curd firmness. The greatest increase in curd firmness was obtained by a combination of reducing milk pH, addition of .02% calcium chloride, and reducing chymosin concentration. High-chymosin concentration at reduced pH decreased coagulation time without substantially increasing curd firmness. Curd disintegration was more apparent at high-chymosin concentration in the poor coagulating samples.

Animals↗
PubMed1984

Bilateral dislocation of the shoulders.

Ninety cases of bilateral dislocation of the shoulders, including seven previously unreported cases are discussed. Forty-nine per cent were due to convulsive seizures or electrocution, 23 per cent were traumatic and 36 per cent were atraumatic. This paper indicates that many attributed to trauma were probably due to unrecognized seizure, and neurological examination is indicated in all cases. Dislocations as a result of seizures or electrocution were often diagnosed late.

Adult↗
PubMed1984

Pharmacokinetics of cefpimizole in normal humans after single- and multiple-dose intravenous infusions.

The pharmacokinetics of cefpimizole (free acid equivalents of cefpimizole sodium), a broad-spectrum cephalosporin antibiotic, were determined after single- and multiple-dose 20-min intravenous infusions of 1, 2, and 4 g. The kinetics of single-dose administration of cefpimizole correspond to a two-compartment model with an average apparent volume of distribution of 20.0 +/- 3.5 liters, a distribution rate constant of 2.24 +/- 1.00 h-1, and a terminal rate constant of 0.358 +/- 0.036 h-1 (half-life, 1.9 h). The total body clearance was 118.6 +/- 20.2 ml/min. The primary route of elimination for cefpimizole was the renal route, with approximately 80% of the administered dose excreted as the parent compound. The elimination rate constant, as calculated from urinary excretion data, was 0.339 +/- 0.043 h-1, which is in close agreement with the terminal rate constant for plasma. Renal clearance of cefpimizole was 96.2 +/- 17.3 ml/min. Dose proportionality over the three dose levels was obtained from area under the plasma curve and cumulative urinary excretion data. The results of the multiple-dose study indicated that no apparent change in the distribution or elimination kinetics of cefpimizole occurred after the administration of 1-, 2-, and 4-g doses for 7 days, three times a day. The kinetics from the multiple-dose study were in close agreement with those from the single-dose study. No accumulation of cefpimizole occurred, and nondetectable levels was observed 24 h after administration of the last dose. Peaks that could be attributed to metabolites of cefpimizole were not observed during high-pressure liquid chromatographic analysis of either plasma or urine specimens.

Adult↗
PubMed1983

Immunoglobulin allotype markers in gluten-sensitive enteropathy.

Immunoglobulin allotype markers and HLA-A, HLA-B, and HLA-DR locus antigens were determined in 30 White patients with gluten-sensitive enteropathy and 30 controls matched for age, ethnic background, and geographic origin. All patients lacking HLA-B8 and HLA-DR3 had the IgG (Gm) immunoglobulin heavy-chain phenotype Gm (f;n;b). Thus, in addition to major histocompatibility locus genes, it appears that genes linked to the immunoglobulin heavy-chain allotype locus on chromosome 14 may influence susceptibility in gluten-sensitive enteropathy.

Adolescent↗
PubMed1983

Association between Crohn's disease and immunoglobulin heavy chain (Gm) allotypes.

Immunoglobulin allotype markers on immunoglobulin G (Gm markers), immunoglobulin A (A2m markers), and kappa light chains (Km markers) were determined in 68 Crohn's disease patients, 39 ulcerative colitis patients, and 1027 healthy controls. Patients and controls were all Caucasians of Northern European origin and not Jewish. The distribution of immunoglobulin heavy-chain (Gm) allotypes differed markedly between Crohn's disease patients and controls. Crohn's disease patients had a significant increase in the frequency of the phenotype Gm(a,x,f;b,g) and the haplotype Gma,x;g. The frequency of Gm phenotypes and haplotypes did not differ significantly between ulcerative colitis patients and controls. Further, there was no significant association between Km markers or A2m markers and inflammatory bowel disease.

Colitis, Ulcerative↗