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Biomedical subjects

M J Hamilton

Publications and source records attributed to M J Hamilton.

At least 55 records · Page 3Linked to original sources
PubMed1992

Bovine mononuclear leukocyte subpopulations in peripheral blood and mammary gland secretions during lactation.

Florescence flow cytometry and monoclonal antibodies were used to analyze the composition of leukocytes from peripheral blood and mammary gland secretions. Samples were obtained from Holstein dairy cows, free of IMI, at six time points during the lactation cycle. The percentage of monocytes in peripheral blood mononuclear cells varied from 15 to 31%; the lowest percentage occurred at the early nonlactation period. The percentage of T lymphocytes from mammary gland secretions varied from 16% during the periparturient period to 62% at late lactation. The B lymphocytes varied from 7% at late lactation to 25% during the periparturient period. Macrophages varied from 21 to 69%; the highest percentage occurred during the periparturient period. The mean ratio of CD4+:CD8+ T lymphocytes in the peripheral blood and mammary gland secretions was 1.53 and .85, respectively. A subpopulation of activated CD8+ T lymphocytes present in mammary gland secretions throughout the lactation cycle coexpressed a new activation molecule, ACT2. Increases in the proportion of CD8+ T lymphocytes were associated with an increase in the percentage of CD8+, ACT2+ T lymphocytes. Activated CD8+ T lymphocytes may play an important role in the regulation and expression of the local immune response to pathogens.

Animals↗
PubMed1990

Intragenomic movement, sequence amplification and concerted evolution in satellite DNA in harvest mice, Reithrodontomys: evidence from in situ hybridization.

Three DNA probes isolated from three species of Reithrodontomys (R. montanus, R. megalotis, R. fulvescens) were used to examine within and among species variation in the chromosomal location of satellite DNA and constitutive heterochromatin. These probes hybridized to the centromeric regions on all chromosomes in six species of the subgenus Reithrodontomys. Additionally, nearly all extra-centromeric C-band positive regions (with the exception of some heterochromatic material on the X and Y) hybridized to these probes. Within the subgenus Reithrodontomys both the chromosomal distribution and organization of satellite DNA has changed throughout evolution. The evolutionary transition has been from a totally centromeric position in R. fulvescens to centromeric and non-centromeric regions in other species that have undergone extensive chromosomal rearrangements from the primitive karyotype for peromyscine rodents. In addition, the monomer repeat of the satellite sequence differs between R. fulvescens (monomer defined by PstI) and the remaining species in the subgenus Reithrodontomys (monomer defined by EcoRI). These results suggest at least two amplification events for this satellite DNA sequence. Models and mechanisms concerned with the homogenization and spread of satellite sequences in complex genomes are evaluated in light of the Reithrodontomys data. From a phylogenetic standpoint, the satellite sequences composing heterochromatic regions were restricted to the subgenus Reithrodontomys, which supports morphological differences used to recognize two subgenera, Reithrodontomys and Aporodon. Probes failed to hybridize to any part of the karyotype of R. mexicanus (subgenus Aporodon) or to seven species from other closely related genera (Baiomys, Neotoma, Nyctomys, Ochrotomys, Onychomys, Peromyscus, Xenomys), some of which are considered as potential sister taxa for Reithrodontomys.

Animals↗
PubMed1990

Identification and characterization of monoclonal antibodies reactive with bovine, caprine and ovine T-lymphocyte determinants by flow microfluorimetry.

Comparative flow microfluorimetric (FMF) analysis was used to identify and characterize 27 monoclonal antibodies (MoAbs) reactive with bovine T-lymphocytes. Determinants present on all circulating T-lymphocytes were recognized by 11 MoAbs, 8 of which blocked E rosette formation. Determinants present on only the BoCD4+ T-lymphocyte subset were detected by 9 MoAbs, while determinants restricted to the BoCD8+ T-lymphocyte subset were recognized by 7 MoAbs. Competitive labeling experiments demonstrated that determinants recognized by subset-specific MoAbs were present on BoCD4 or BoCD8 molecules. Comparative studies revealed that some determinants, both pan-T specific and subset-specific, were conserved on homologous (orthologous) molecules expressed on leukocytes from other species of ruminants. Polymorphism was evident with several determinants.

Animals↗
PubMed1990

Characterization of monoclonal antibodies to feline T lymphocytes and their use in the analysis of lymphocyte tissue distribution in the cat.

We describe the development of three monoclonal antibodies to feline T lymphocytes. Antibody 1.572 stains 93% of feline thymocytes, 49% of lymph node, and 65% of spleen lymphocytes. Two-color analysis shows 1.572 does not stain Ig-bearing cells, and 1.572-positive lymphocytes plus Ig-positive lymphocytes make up approximately 90% of peripheral blood lymphocytes (PBL), suggesting that 1.572 is a pan-T cell marker. The other two monoclonal antibodies, 3.357 and CAT30A, stain a smaller population of thymocytes (59%) of which 40% express both antigens. The 3.357 antigen is found on 23% of lymph node and 47% of spleen lymphocytes, while the CAT30A antigen is found on 29% of lymph node and 19% of spleen lymphocytes. Two-color analysis shows that 3.357 and CAT30A stain mutually exclusive subpopulations of 1.572-positive cells. Using thymocytes as an antigen source, antibody 3.357 precipitated a molecule of 66,000 molecular weight (Mw) under nonreducing conditions and a heterodimer of 32,000 and 34,000 under reducing conditions, suggesting that 3.357 recognizes the feline CD8 homologue. Antibody CAT30A precipitated a molecule of 55,000 Mw under both reducing and nonreducing conditions, which suggests it recognizes the feline CD4 homologue. Analysis of PBL profiles of 35 normal cats using the three monoclonal antibodies indicates that the distribution of feline PBL subpopulations is similar to man, including the CAT30A:3.357 ratio (1.74), which is identical to reported CD4:CD8 ratios in man. Based on these data, the feline CD4 and CD8 homologues are similar to those reported in other species.

Animals↗
PubMed1990

A randomised double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy.

The efficacy of lamotrigine (LTG), a new antiepileptic drug (AED) chemically unrelated to drugs in current use, was evaluated in 21 in-patients (18 males, 3 females; mean age 34.6; range 23-42 years) with severe refractory epilepsy. An add-on double-blind placebo-controlled crossover design was used, with 12 week treatment periods, and a 6 week washout period. Subjects were allocated to 1 of 2 dosing schedules according to their concomitant AEDs. Doses were increased according to clinical response. Although there was no significant reduction in total seizure count during the lamotrigine treatment period compared to placebo, there appears to be a drug effect as there was a marked reduction in generalized tonic-clonic seizures in favour of lamotrigine in the last 4 weeks of the treatment period. There was no significant difference in volunteered adverse experiences during active and placebo treatment. Concomitant serum AED concentrations, biochemical and haematological parameters were unaffected by lamotrigine treatment.

Adult↗
PubMed1987

Genetic differentiation among cottontails from isolated playa basins.

Protein variation in 182 Sylvilagus floridanus from 19 playa basins in Castro Co., Texas was examined using starch-gel electrophoresis. Heterozygote deficiencies were noted for all populations. This heterozygote deficiency may be due to differential selection against heterozygous individuals over the winter months. Results of F-statistics indicated a significant degree of population differentiation at six loci. Nei's genetic distance between populations ranged from 0.20 to 0.388 and a significant association between genetic distance and linear geographic distance among playas was found. These results suggest that genetic exchange and long-distance dispersal may be hindered by expanses of unsuitable habitat.

Animals↗
PubMed1987

The effects of acrivastine (BW825C), diphenhydramine and terfenadine in combination with alcohol on human CNS performance.

Two studies were performed to measure the effects of acrivastine (BW825C), an antihistamine, in combination with alcohol on the central nervous system. In one study acrivastine 8 mg, diphenhydramine 50 mg and alcohol 32 ml were administered alone and in combination and compared with placebo. In a second study terfenadine 60 and 120 mg and acrivastine 4 and 8 mg combined with alcohol 32 ml were compared with placebo and alcohol alone. Each study was a double-blind, randomised cross-over design using twelve healthy volunteers. Adaptive tracking, reaction time, body sway, eye movements and subjective effects were measured at intervals after treatments. Acrivastine 8 mg alone did not affect any of these measures in contrast with diphenhydramine. Acrivastine in combination with alcohol caused significantly more impairment of some of the tests than placebo or alcohol alone, but significantly less than diphenhydramine/alcohol, which also affected more tests. In the second study no significant differences were seen between the effects of alcohol alone and combinations of either terfenadine or acrivastine with alcohol. It was concluded that acrivastine 8 mg alone did not impair CNS performance in the tests used. In combination with alcohol significant impairment was seen, but this was less pronounced than after diphenhydramine/alcohol. The second study failed to demonstrate differences between drug/alcohol combinations and alcohol alone confirming that the effect of acrivastine in combination with alcohol is small.

Adolescent↗
PubMed1987

Lamotrigine: single-dose pharmacokinetics and initial 1 week experience in refractory epilepsy.

Twenty-three residential patients on chronic antiepileptic drugs (AEDs) were entered into an open study of 4 weeks duration. Baseline variables and seizure frequency were determined in the first week. All patients received a single dose of lamotrigine in the second week to determine single-dose pharmacokinetic parameters. Twenty patients then received daily or twice daily lamotrigine for a week. Post-treatment seizure frequency was observed for a further week. Patients taking liver enzyme inducing antiepileptic drugs showed a mean lamotrigine plasma elimination half-life (T1/2) of 14 h (+/- 7) (T1/2 of normal volunteers = 24 h) and those taking sodium valproate and an inducing AED showed a mean lamotrigine T1/2 of 30 h (+/- 10). The plasma concentrations of co-administered sodium valproate, phenytoin, carbamazepine, phenobarbitone and primidone were not altered by 1 week lamotrigine dosing. There was a significant reduction in complex partial seizures in the treatment week compared with baseline. Some patients showed a marked increase in seizure frequency on stopping lamotrigine. There was an increase in reports of drowsiness during lamotrigine administration, but there were no clinically significant changes in any safety measure.

Adolescent↗
PubMed1987

Problems in using Robertsonian rearrangements in determining monophyly: examples from the genera Tatera and Gerbillurus.

Chromosomal banding data on three species of Tatera from Kenya significantly alter the previous hypothesis of relationships between and within the genera Tatera and Gerbillurus based on cladistic analyses and the rule of parsimony (Qumsiyeh, 1986b). Of the many possible hypothetical relationships, the most parsimonious tree showed three homoplasies and allowed the genus Gerbillurus to be paraphyletic. The alternative trees, depicting larger number of homoplasies but with homoplasies restricted to fusion or fission events, were compatible with the morphological data in supporting the monophyly of Gerbillurus. To choose between the hypothesis based on the most parsimonious chromosomal tree and those supported by both morphology and slightly less parsimonious chromosomal trees, we performed an electrophoretic study on this group of gerbils. The conclusions are that the genus Gerbillurus is monophyletic and represents a branch that is closely related to the T. robusta group of Taterillini. The study documents that fissions and fusions must have occurred frequently and that in some cases the same fusions were acquired in two independent lineages in numbers exceeding those that are predicted by strict parsimony. The results raise questions about the validity of systematic conclusions based solely on fusion/fission data and utilizing the parsimony criterion.

Animals↗
PubMed1985

Pharmacodynamic and pharmacokinetics of BW 825C: a new antihistamine.

The new H1-receptor antagonist BW 825C and triprolidine (2.5 and 5 mg) were administered to 12 healthy male volunteers in a double blind placebo controlled, balanced, crossover design. Histamine antagonism was measured by assessment of flare and weal areas after intradermal injection of histamine. The 2 compounds were approximately equipotent in blocking the flare and weal response to intradermal histamine and had a similar duration of action. Triprolidine impaired performance of vigilance and reaction time (p less than 0.05) compared with placebo while BW 825C did not. Drowsiness measured using visual analogue scales followed both triprolidine treatments, but not BW 825C. BW 825C had a plasma half-life (t1/2) of 1.7 +/- 0.2 h and triprolidine of 4.6 +/- 4.3 h. The peak plasma level of BW 825C was approximately 6 times that of triprolidine. It was concluded that BW 825C might be a clinically active H1-antagonist with reduced sedative side-effects.

Adult↗
PubMed1985

Pharmacokinetics and Pharmacodynamics of procyclidine in man.

The pharmacokinetics and pharmacodynamics of procyclidine (10 mg) after oral and intravenous administration were studied in six healthy volunteers. Treatment order was randomised and the study was placebo-controlled and conducted blind. After oral dosing the mean peak plasma concentration was 116 ng/ml and mean bioavailability was 75%. After both oral and intravenous dosing the mean values for the volume of distribution, total body clearance and plasma elimination half-life of procyclidine were in the order of 1 l/kg, 68 ml/min and 12 h respectively. Autonomic effects were maximal within 0.5 h of intravenous administration and at about 1-2 h after oral dosing. Significant effects on pupil diameter, visual near point, salivary secretion and heart rate occurred after intravenous treatment and similar but less marked effects occurred after the oral dose. Significant autonomic effects were still detectable 12 h after both forms of treatment.

Administration, Oral↗
PubMed1985

Sources of proteins in human bile.

The proteins of 46 human bile specimens, collected by several different routes have been studied by crossed immunoelectrophoresis, by rocket immunoelectrophoresis and by radioimmunoassay. The results were analysed by plotting the variation in the bile: plasma ratio of particular proteins against molecular weight and by examination of the correlation between the concentrations of different proteins in the biles of different patients. Our results show that the majority of human bile proteins derive from plasma although bile specific proteins are always present. The majority of plasma proteins appear to enter bile by a 'sieving' mechanism which results in an inverse relationship between the bile: plasma ratio and the molecular weight. In addition there was a very high degree of correlation between the biliary concentrations of alpha 2-macroglobulin, IgG, haptoglobin, haemopexin, albumin, prealbumin, and orosomucoid. A number of other proteins namely thyroxine binding globulin, GC globulin and alpha 2HS-glycoprotein appeared in bile at concentrations greater than those expected if entry is by the sieving mechanism. These three proteins, however, are of rather low molecular weight and the reason for the lack of correlation appears to be individual variation in the 'pore size', presumably reflecting variation in the porosity of tight junction between hepatocytes. Although the majority of human bile proteins would appear to enter bile by a molecular weight-dependent pathway, four proteins, namely secretory IgA, IgM, haemoglobin and caeruloplasmin, showed significant deviation from the predicted relationship and probably enter bile at least partly by transport across cells. The concentration of beta 2-glycoprotein I was also much greater than expected from its molecular weight. The reason for this is not yet clear but may well reflect a very efficient and specific transport mechanism.

Bile↗
PubMed1984

Serum testosterone levels in young normal horses.

Serum testosterone levels were measured in normal young male horses (29 to 34 weeks old). No differences were found between gelded and intact males. The values for all the horses were low. On the basis of their testosterone levels, all the horses were prepubertal.

Journal Article↗
PubMed1984

Estimation of the stereoscopic threshold utilizing perceived depth.

Recent reports in the literature indicate that a random-dot style of stereoscopic test is the most accurate method of assessing stereoscopic threshold [Cooper, J., Feldman, J. and Medlin, D. (1979) J. Am. optom. Ass. 50, 821-825]. While this is undoubtedly true for those who can respond to the test, it is less so for very young, infirm or other patients who do not or cannot have the requisite attention span. This experiment finds that the amount of perceived depth seen on a test like the Titmus fly correlates very accurately with the measured stereoscopic threshold and can therefore be used as a measure of the threshold without having to employ the entire testing procedure of the random dot tests. The regression equation derived from the data is presented, as well as a table that allows a practitioner to estimate the stereoscopic threshold from the amount of perceived depth on a common stereo test: the Titmus fly.

Adult↗
PubMed1984

The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man.

The effects of bupropion and ethanol were examined alone and in combination in a placebo controlled, double-blind, crossover study in 12 healthy volunteers. Results were subjected to analysis of variance and differences of p less than 0.05 taken as significant. In the main study using the Wilkinson auditory vigilance test, no active treatment or combination of treatments produced significant change compared with placebo. However, when compared with bupropion 100 mg, vigilance was significantly impaired by 32 ml alcohol alone though not when combined with bupropion. No significant changes in reaction time or short term memory occurred. Visual analogue scales indicated that the subjects were mentally slower after alcohol 32 ml than after placebo. Combination of bupropion 100 mg with alcohol 32 ml abolished this difference. A similar pattern occurred with group ratings indicating mental sedation. Subjects were clearly able to differentiate between the 16 ml and 32 ml doses of alcohol when assessing their degree of inebriation. Combination of bupropion with alcohol made no difference to the ratings of inebriation. The top dose of alcohol tended to increase energy in the low frequency EEG bands. Combination of the top alcohol dose with bupropion, however, produced a significant reversal with lowered energy in the 4-7.5 Hz band. Combination of bupropion with alcohol failed to change the blood alcohol concentration achieved.

Adult↗
PubMed1983

Effects of bupropion, nomifensine and dexamphetamine on performance, subjective feelings, autonomic variables and electroencephalogram in healthy volunteers.

Bupropion, a novel antidepressant, has been compared with nomifensine and dexamphetamine in a controlled double blind trial in 12 healthy volunteers. Signals detected in an auditory vigilance test were increased by dexamphetamine 5 and 10 mg when compared with lactose dummy, but unaffected by bupropion 100 and 200 mg and nomifensine 100 mg. Auditory reaction time was decreased by dexamphetamine but unaffected by bupropion and nomifensine. Heart rate was increased after all active treatments but the largest rise followed dexamphetamine 10 mg which differed from both lactose dummy and all other active treatments. Systolic blood pressure was higher after dexamphetamine 10 mg than all other treatments, none of which differed from lactose. No changes occurred in diastolic blood pressure. Pupil size increased after dexamphetamine 10 mg but no changes followed other treatments. Visual analogue scales showed that subjects were more alert, attentive, proficient, excited, interested and elated after dexamphetamine but no changes followed bupropion or nomifensine. Subjects were able to recognise that they had received an active drug only after dexamphetamine 10 mg. Increased activity was seen in the 7.5-13.5 Hz and 13.5-26 Hz frequency bands of the electroencephalogram after dexamphetamine 10 mg but not after bupropion or nomifensine. These findings in man suggest that neither of these two, non-sedative antidepressants possess amphetamine-like stimulant activity, and are discussed in relation to the animal pharmacology of the drugs.

Adult↗
PubMed1983

A controlled trial of cinromide.

A double-blind controlled trial of cinromide in 25 adult subjects with refractory epilepsy using the maximum tolerated dose showed that it possessed no significant antiepileptic properties.

Adolescent↗