Flurbiprofen warning.
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Biomedical subjects
Publications and source records attributed to D Bennett.
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The genetic diversity between the t12 and tw5 haplotype chromosomes was studied by analyzing the molecular organization of the H-2K region. Twenty-one cosmid clones spanning over 150 kb of the H-2K region of both t-haplotypes were defined, and high resolution restriction maps were determined. Detailed comparison of the t12 and tw5 restriction maps revealed the following. (i) The H-2K regions of both t-haplotypes retain a very similar molecular organization to that reported for B10, BALB/c and AKR. The nucleotide sequence diversity estimated from restriction site polymorphism is 0.68% between the t12 and tw5 haplotypes; these two t-haplotypes are no more similar to one another than BALB/c is to AKR. (ii) Genetic recombination is strongly implicated in generating H-2 polymorphism. (iii) Genetic polymorphisms, defined as small restriction fragment size differences, are observed at multiple sites along the H-2K region. An Alu-like B2 sequence and BAM5-R homologous sequence were identified as the inserted/deleted DNA segments of two of these sites, suggesting that insertion/deletion of mobile elements is a general mechanism for generating genetic diversity.
Plasma colloid osmotic pressure (COP) has been calculated from both serum albumin concentration and plasma total protein concentration. These values have been compared to those measured directly using a membrane-transducer oncometer in a group of normal subjects, in a group of critically-ill patients with a variety of primary diagnoses and in a group of hypovolaemic patients before and after plasma volume replacement with 6% hydroxyethyl starch solution. In the normal samples, COP calculated from albumin (COPalb) underestimated the measured COP (COPm) by mean of 2.0 mmHg (p less than 0.002), with correlation coefficient r = 0.39(n/s). Similarly, the COPalb underestimated COPm by a mean of 5.7 mmHg (p less than 0.001) in the critically ill patient group; r = 0.38 (p less than 0.02). Furthermore, in the patients receiving plasma volume replacement serum albumin concentration fell by 13.1% (p less than 0.001) whilst COPm increased by 11.5% (p less than 0.002). In the normal subjects COP calculated from total protein concentration (COPtp) underestimated the COPm by 1.5 mmHg (p less than 0.02) with r = 0.65 (p less than 0.01). Conversely, in the patient samples, mean COPtp overestimated COPm by 3.5 mmHg (p less than 0.001) with r = 0.73 (p less than 0.002). We conclude that COPalb is an inadequate estimate of COPm particularly in patients where its use may have important clinical consequences. COPtp provides a reasonable estimate of COPm in normal subjects but in patients samples, where albumin: globulin ratio is low COPtp overestimates substantially in many cases. We advocate the direct measurement of COP in critically-ill patients.
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An indirect immunofluorescence test with sections of rat liver as a substrate, proved useful in detecting antinuclear antibodies (ANA) in the dog. A specific anti-canine IgG reagent conjugated with fluorescein isothiocyanate was used. A proportion of normal dogs gave positive reactions at low titres. The presence of ANA was one of the criteria used to diagnose canine systemic lupus erythematosus. Some dogs within a general hospital population were also positive for the auto-antibody. The indirect immunofluorescence test with Trypanosoma brucei as a substrate was insensitive. The LE-cell test was laborious and insensitive. A commercial latex slide agglutination test used for detecting ANA in man gave false positive and false negative results in the dog. A commercial radioimmunoassay used in man gave many false positive results. A similar assay with synthetic DNA gave encouraging results and is worthy of further study.
A modified Rose-Waaler test with sheep red blood cells coated with canine IgG was found satisfactory for detecting rheumatoid (antiglobulin) factor (RF) in dog serum. Low titres of RF were found in some normal dogs. Most dogs with rheumatoid arthritis were positive for RF at titres of 1 in 40 or greater. A small proportion of dogs with diseases other than polyarthritis were also positive for RF. A commercial slide agglutination test used for detecting human RF was unsatisfactory for the dog, giving false positive and negative reactions. A latex tube agglutination test with latex particles coated with dog IgG was developed but non-specific agglutination was a constant technical problem.
A field experiment was carried out to investigate the fate and the extent to which food chain transfer of a PCB congener (2,5,4'-trichlorobiphenyl; 3-CB) could affect its potential for bioaccumulation. Three 35-m3 ponds were each stocked with 25 rainbow trout (a carnivore) and 20 grass carp (a herbivore). 3-CB was supplied to each pond at a nominal concentration of 14 micrograms liter-1. Samples of water, sediment, grass carp, rainbow trout, aquatic plants, and invertebrates were removed at intervals from 0 to 28 days after treatment and residues of 3-CB were determined using gas-liquid chromatography with electron-capture detection. The fate of 3-CB in the ponds was determined by transport rather than degradation processes. Evaporation accounted for 86-87% loss and sorption onto sediment and biota for 11-12% loss of 3-CB from the pond water after 28 days. The kinetics of transport between water, air, sediment, and biota were studied after fitting the data to a three-compartment model. This model was used to calculate rates of evaporation (ke) and sorption. The calculated value for ke was in good agreement with predictions based on fundamental relationships between Henry's constant, windspeed, and ke. Residues of 3-CB in rainbow trout accumulated to a significantly greater extent (P less than 0.05) than in grass carp. This difference could not be explained by differences in growth rates, distribution of lipids, or by a difference in rates of metabolism. The most plausible explanation is that there was a difference in accumulation of 3-CB residues via the food chain. This experimental work supports the conclusion, suggested by a modeling approach of other workers, that food chain accumulation of PCBs can be an important route for uptake when environmental concentrations are very low.
This experiment assessed the transfer effect of Pavlovian conditioning with d-amphetamine sulfate (1 mg/kg) on morphine's activity effects. Prior experience with amphetamine resulted in higher levels of activity when challenged with morphine (10 and 20 mg/kg). This interactive effect of amphetamine, however, was present only in those animals who had experienced amphetamine paired with the activity test situation. Animals who had received equivalent doses of amphetamine unpaired with the testing environment did not differ from drug-naive control animals. Analysis of predrug activity levels revealed a conditioned activity response in paired animals compared to the controls. These findings suggest that the response interaction between drug conditioned responses and drug unconditioned responses is an important determinant of cross-drug effects between drugs of different pharmacological classes.
Restriction fragment polymorphisms were used to order the alpha A-crystallin locus (Crya-1) relative to other genes in mouse t-chromatin and to investigate the relatedness of alpha-A-crystallin sequences among different t-haplotypes. Analysis of DNA from t-recombinant mice mapped Crya-1 to the K end of the H-2 complex and within the distal inverted region characteristic of t-haplotypes. Hybridization with Crya-1 cDNA revealed three distinct phenotypic groups among the 17 different t-haplotypes studied. A majority (9 of 17) of the t-haplotypes were classified into a novel group (Crya-1t) characterized by restriction fragments apparently unique to t-chromosomes and therefore thought to contain alpha A-crystallin sequences descended from the original t-chromosome. A second group of t-haplotypes had restriction fragment patterns indistinguishable from those observed among many common inbred strains of mice of the Crya-1a type, and a third restriction fragment pattern, observed only in the tw121 haplotype, was indistinguishable from the fragment pattern for C3H/DiSn (Crya-1b) and several other inbred strains of mice. Thus, with respect to sequences around the Crya-1 locus, different t-haplotypes show restriction fragment polymorphisms, some of which are comparable to those found in wild-type chromosomes and provide further evidence for genetic heterogeneity in DNA from the distal region of t-haplotypes.
A new recessive mutation affecting tail length is described. It is unlinked to the T/t-complex on chromosome 17 and yet it shows cumulative phenotypic effects with several t-complex mutations: T, TCu, tct and Fuki. It does not interact with five different nonchromosome 17 mutations that affect tail length. Thus, t-int is a tail modifier with surprisingly specific interactions.
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Previous research has suggested that dyslexics treated with piracetam have shown improvements in reading skills, verbal memory and verbal conceptualizing ability, feature analysis, and processing of letter-like stimuli. Two hundred twenty-five dyslexic children between the ages of 7 years 6 months and 12 years 11 months whose reading skills were significantly below their intellectual capacity were enrolled in a multicenter, 36-week, double-blind, placebo-controlled study. Children of below average intelligence, with abnormal findings on audiologic, ophthalmologic, neurologic, psychiatric, and physical examinations, who were emotionally disturbed or educationally deprived and who had recently been treated with psychoactive medication were excluded from the trial. Piracetam was well tolerated, with no serious adverse clinical or laboratory effects reported. Piracetam-treated children showed significant improvements in reading ability (Gray Oral Reading Test) and reading comprehension (Gilmore Oral Reading Test). Treatment effects were evident after 12 weeks and were sustained for the total period (36 weeks).
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Serum concentrations of C-reactive protein (CRP) in dogs with various diseases or undergoing various procedures were measured by specific immunoassay. In 20 healthy dogs from various sources, values were all less than 5 mg/L, but in 22 healthy dogs from a single source, values ranged from less than 5 mg/L in 14 dogs and from 8 to 67 mg/L in 8 dogs. Increased concentrations of serum CRP were attained 24 hours after injection of casein (n = 9; median 188 mg/L), ovariohysterectomy (n = 11; median, 144 mg/L), or elective, nonacute orthopedic surgery (n = 10; median, 83 mg/L). After inoculation of Leptospira interrogans serovar canicola (n = 5), the behavior of serum CRP as an acute-phase reactant provided a sensitive and precise objective reflection of in vivo response. The CRP concentration in random single-serum samples from 73 dogs with other inflammatory and noninflammatory disorders ranged from normal (less than 5 mg/L) to 246 mg/L and generally correlated with the extent and activity of disease.
Left ventricular (LV) function was assessed by Doppler ultrasound measurement of ascending aortic blood velocity and maximal acceleration in 165 patients 3 to 4 weeks after acute myocardial infarction (AMI); all were undergoing routine 12-lead electrocardiogram exercise stress testing. Patients were grouped according to electrocardiographic stress test response; a positive response was defined as at least 1 mm of ST-segment depression in any lead. The Doppler velocity signal yielded 3 variables of interest: peak velocity, maximal acceleration (an index of inotropic state) and the systolic velocity integral (an index of stroke volume). All 3 Doppler ejection variables were significantly lower at peak exercise in patients with a positive electrocardiographic stress test response than in those with negative response, with maximal acceleration showing the most significance (p less than or equal to 0.001). Coronary angiography was performed in 63 of the 67 patients with positive responses, and patients were separated into 2 groups according to extent of coronary artery disease (CAD): 1- and 2-vessel or 3-vessel CAD. Peak velocity and maximal acceleration were significantly lower in patients with 3-vessel CAD than in those with 1- and 2-vessel CAD (p less than or equal to 0.01 and p less than or equal to 0.01). Discriminant analysis showed maximal acceleration and peak velocity values at peak exercise to be 65% predictive of 3-vessel CAD, onset time to ST-segment depression was 74% predictive and the combination of Doppler and electrocardiographic variables increased 3-vessel CAD predictive value to 80%.(ABSTRACT TRUNCATED AT 250 WORDS)
The extent to which immune processes contribute to senescence-related neurological/behavioral impairment was examined using an adoptive transfer procedure. C57BL/6 mice aged 22 to 24 months showed impaired ability for acquisition of an active avoidance response when compared with younger mice aged 3 months. An immunofluorescence assay of the sera of these mice indicated that only sera from the senescent mice reacted with brain antigen. When tested three months following irradiation and receipt of bone marrow/spleen cell suspensions from senescent mice, young mice showed senescence-like serum-brain reactivity and declines in their abilities to acquire learning. Young control mice receiving cell suspensions from age-matched donors showed no evidence of serum-brain reactivity or learning deficits, suggesting that impaired learning was related to acquisition of aged immunity and not a nonspecific effect of the transfer procedure. These findings indicate that immune processes may be involved in the etiology of senescence-related neurological/behavioral dysfunctions.
Increased levels of amidase acting on a tissue-kallikrein selective substrate, Val.Leu.Arg.pNA, with an activity optimum at pH9, were detected in blood-free inflamed tissues from adjuvant arthritic rats (p less than 0.01). The component of this activity resistant to inhibition by soybean trypsin inhibitor (SBTI) also greatly increased (p less than 0.05). Both the SBTI-sensitive and SBTI-resistant components were inhibited by aprotinin (93% and 72% respectively). Kallikrein-like amidase also increased in inflamed synovia from seropositive rheumatoid, and osteoarthritic dogs when compared with healthy canine synovia. This increase was parallelled by an increase in kinin-forming enzyme which was also measured in rheumatoid and healthy animals and this activity was inhibited 72% by aprotinin. Total kallikrein-like amidase also increased 989% (p less than 0.05) in synovia from seropositive rheumatoid human patients, compared with healthy synovial tissue. Evidence is presented indicating that the origin of this enzymic activity may be plasma kallikrein.