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Biomedical subjects

R Hunter

Publications and source records attributed to R Hunter.

At least 73 records · Page 4Linked to original sources
PubMed1989

Free sphingosine formation from endogenous substrates by a liver plasma membrane system with a divalent cation dependence and a neutral pH optimum.

Long-chain (sphingoid) bases may serve as another category of "lipid second messenger" because they inhibit protein kinase C and affect multiple cellular functions. Free sphingosine has been found in rat liver (Merrill, A. H., Jr., Wang, E., Mullins, R. E., Jamison, W. C. L., Nimkar, S., and Liotta, D. C. (1988) Anal. Biochem. 171, 373-381); hence, this study determined if liver plasma membranes contain free long-chain bases and have the ability to form them from endogenous enzymes and substrates. Isolated plasma membranes contained 0.45 nmol of sphingosine/mg of protein which, based on the recovery of the membranes, was equivalent to 3.5 +/- 1.2 nmol/g of liver and at least half of the total free sphingosine in liver. When the membranes were incubated at 37 degrees C, the amount increased at an initial rate of 5-25 pmol/min/mg, resulting in a 2-3-fold increase over an hour. Sphingosine formation required divalent cations, was optimal at neutral to alkaline pH, and was temperature-dependent. Activities with these characteristics were not identified in microsomes or lysosomes (lysosomal activities with acidic pH optima were detected, however); hence, they appear to reflect a separate plasma membrane system. Sphingosine formation was stimulated by ceramides either added exogenously or formed endogenously by treating the membranes with sphingomyelinase (but not endoglycoceramidase). Sphingomyelin hydrolysis to ceramide was also observed during incubation of the plasma membranes alone. Some of the properties of this system resembled the neutral sphingomyelinase and ceramidase activities of liver. While the physiological significance of this endogenous sphingosine is not known, this system has the appropriate subcellular location to provide sphingosine as a participant in signal transduction.

Animals↗
PubMed1989

Structural requirements for long-chain (sphingoid) base inhibition of protein kinase C in vitro and for the cellular effects of these compounds.

Sphingosine, sphinganine, and other long-chain (sphingoid) bases inhibit protein kinase C in vitro and block cellular responses to agonists that are thought to act via this enzyme. To gain further insight into the mechanism of this inhibition, a series of long-chain analogues differing in alkyl chain length (11-20 carbon atoms), stereochemistry, and headgroup were examined for (a) inhibition of protein kinase C activity in vitro, (b) the neutrophil respiratory burst in response to phorbol myristate acetate (PMA), (c) the PMA-induced differentiation of HL-60 cells, and (d) the growth of Chinese hamster ovary cells. In every instance, the effects were maximal with the 18-carbon homologues, which are the same length as the predominant naturally occurring long-chain base (sphingosine). The lower potency of the shorter chain homologues was partially due to decreased uptake by cells. Small differences were obtained with the four stereoisomers of sphingosine (i.e., D and L forms of erythro- and threo-sphingosine), with N-methyl derivatives of the different sphingosine homologues, and with simpler alkylamines (e.g., stearylamine). The potency of the different headgroup analogues may be affected by the degree of protonation at the assay pH. The pKa of sphingosine was measured to be 6.7; the pKa varied among the analogues. These findings establish that the major structural features required for inhibition of protein kinase C and cellular processes dependent on this enzyme are the presence of a free amino group and an aliphatic side chain and that other groups have more subtle effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A new subgroup 2 bovine adenovirus proposed as the prototype strain 10.

A slowly growing subgroup 2 bovine adenovirus (BAV) strain designated Ruakura 78-5371 was isolated from a yearling heifer with systemic adenovirus infection. Cross neutralization tests and restriction endonuclease analysis of the viral DNA showed the virus to be distinct from the other 9 recognised types of BAV. It is proposed that this strain should be regarded as the prototype strain of the new type BAV-10.

Adenoviridae↗
PubMed1989

The pattern of function-related regional cerebral blood flow investigated by single photon emission tomography with 99mTc-HMPAO in patients with presenile Alzheimer's disease and Korsakoff's psychosis.

Single photon emission tomography (SPET) with the lipophilic blood flow marker 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) has been used to determine regional uptake of radiolabel into brain regions of patients with presenile Alzheimer's disease and Korsakoff's psychosis, and age-matched controls. Using occipital cortical uptake as reference area, the pattern of relative regional cerebral blood flow (rCBF) was determined in other cortical areas and basal ganglia. In Alzheimer's disease, reduction in rCBF occurred most strikingly in posterior temporal and parietal areas. By contrast, in Korsakoff's psychosis, posterior temporal rCBF was maintained, although there was a trend to reduced tracer uptake in other cortical areas. These impairments of flow were correlated with impairments of neuropsychological function. In Alzheimer's disease, left posterior temporal and left parietal regions in particular showed rCBF to be strongly correlated with most aspects of cognitive function. In Korsakoff's psychosis, however, impaired flow in frontal regions was correlated with impaired performance on tests of memory and orientation. The findings in Alzheimer's disease show quantitative parallels with those from studies using Positron Emission Tomography (PET), and extend our understanding of the relationship between cognition and regional brain function in dementia. The findings in Korsakoff's psychosis offer the first direct evidence linking frontal lobe dysfunction with the cognitive impairment seen in the disorder.

Adult↗
PubMed1989

Luteinizing hormone responses to luteinizing hormone releasing hormone (LHRH) in acute mania and the effects of lithium on LHRH and thyrotrophin releasing hormone tests in volunteers.

The endocrine responses to Luteinizing Hormone Releasing Hormone (LHRH) of eight drug-free males with mania were determined. Basal levels of Luteinizing Hormone (LH) and the plasma levels following injection of LHRH were elevated in patients compared with controls; Follicle Stimulating Hormone (FSH) and testosterone were not different. Elevated levels of LH have been described previously in recovered manic patients and have been suggested to be state-independent features of mania. In order to clarify the status of this finding, the effects of lithium administration upon hormone responses to LHRH in six male volunteers were also investigated, together with the effects upon Thyrotrophin Releasing Hormone (TRH) stimulation of Thyroid Stimulating Hormone (TSH) and prolactin release. Lithium increased the basal levels of LH and levels after injection of LHRH without effect upon FSH and testosterone. Lithium also increased basal and TRH stimulated release of TSH and basal prolactin levels. Lithium was without effect upon prolactin responses to TRH. The results are discussed in relation to current information on the mechanism of lithium's action. The implications for neuroendocrine work on recovered patients taking lithium are also explored.

Adult↗
PubMed1989

Blood-lead levels and children's behaviour--results from the Edinburgh Lead Study.

The effect of blood-lead on children's behaviour was investigated in a sub-sample of 501 boys and girls aged 6-9 years from 18 primary schools within a defined area of central Edinburgh. Behaviour ratings of the children were made by teachers and parents using the Rutter behaviour scales. An extensive home interview with a parent was also carried out. Multiple regression analyses showed a significant relationship between log blood-lead and teachers' ratings on the total Rutter score and the aggressive/anti-social and hyperactive sub-scores, but not the neurotic sub-score when 30 possible confounding variables were taken into account. There was a dose-response relationship between blood-lead and behaviour ratings, with no evidence of a threshold.

Aggression↗
PubMed1989

Cerebral vascular transit time in Alzheimer's disease and Korsakoff's psychosis and its relation to cognitive function.

The cerebral vascular transit time of 17 patients with pre-senile dementia of the Alzheimer type (ATD), nine abstinent patients with alcoholic Korsakoff's psychosis (KOR), and ten age-matched controls was determined by the bolus intravenous injection of pertechnetate. A gamma camera was used to estimate the median transit time (MTT) of the radioactive bolus in a planar (non-tomographic) projection normal to the vertex. The spread of the bolus arriving at the aortic arch was measured independently by a single external detector over the chest, and correction made for the transit time of this input function in calculating the net MTT for the head. Both ATD and KOR groups showed lengthened net MTTs, compatible with reduced cerebral blood flow, and which were correlated with reduced cognitive function. It is concluded that the method employed gives a simple, inexpensive estimate of function-related blood flow to the brain in pre-senile dementia.

Aged↗
PubMed1988

Factors influencing lead concentrations in shed deciduous teeth.

Data collected for the Edinburgh Lead Study have been used to investigate lead concentrations in children's naturally shed deciduous teeth. A within-child multiple-regression analysis has shown that the upper jaw has a higher concentration of lead than the lower, and that there is a gradient of decreasing concentration from the front to the back of the mouth. Even after the effects of jaw and tooth type have been allowed for, the concentration is still found to be negatively correlated with the weight of the tooth and with the age at which the tooth was shed. No statistically significant effects could be attributed to caries, fillings, or the incomplete resorption of roots. A single-valued index of tooth lead has been derived for each child, taking into account the fact that children gave different types of teeth.

Age Factors↗
PubMed1988

Fertility and hormonal responses to temporary relief of heat stress in lactating dairy cows.

The influence of temporary cooling on pregnancy rate and ovarian secretion of cortisol, estradiol and progesterone in Holstein cows was evaluated during the months of June to September. Cows were randomly assigned to one of five treatment groups: 1) evaporative cooling, 8 d; 2) evaporative cooling, 16 d; 3) refrigerated air conditioning, 8 d; 4) refrigerated air conditioning, 16 d and 5) controls maintained outdoors with access to shade. Estrus was synchronized by giving two injections of prostaglandin (25 mg). Cows in the cooled groups were placed in box stalls at the time of the second prostaglandin injection, allowing them to be cooled for approximately 3 d prior to breeding. Blood samples were taken on days 0, 5, 10, 15, 20 and 25 postbreeding and serum was analyzed for estradiol, cortisol, progesterone and a pregnancy-specific protein. Pregnancy rates as determined by palpation per rectum at 40 to 60 d post breeding were not different between cows in cooled treatments, regardless of duration or type of cooling. Pregnancy rate was higher (P<0.05) in cooled as compared to control cows. Serum progesterone concentrations were higher on Day 15 in cooled cows as compared to control cows. No differences in serum estradiol or cortisol concentrations were observed between cooled and control cows. Pregnancy-specific protein determinations indicated that 50% of both cooled and control cows conceived. Results indicate that temporary cooling increased pregnancy rates by increasing embryonic survival rates.

Journal Article↗
PubMed1988

Steady-state pharmacokinetics of lithium carbonate in healthy subjects.

1. The pharmacokinetics of lithium in six healthy volunteers stabilised on lithium were investigated and appropriate pharmacokinetic parameters calculated. 2. The results illustrate important differences in single and multiple dose lithium pharmacokinetics; the implications for minimising lithium-induced renal damage are discussed.

Adult↗
PubMed1988

Rescreening of a group at high risk for colorectal neoplasia using immunochemical tests for faecal occult blood.

The results of a screening programme for colorectal neoplasia in a high risk group using an immunochemical test for blood has been reported recently. This test is known as the faecal human haemoglobin (FHH) test. This paper reports the results of rescreening this group after an interval of 1-2 years. The FHH test was compared with a paper disc method. All individuals with positive tests were investigated and those with negative tests were offered investigation. The results confirm the value of the FHH test in screening a high risk group: 19 individuals in 1,153 participants were found to have a significant neoplasm (1.6%). The predictive value of the test for a significant neoplasm was 42%. A false negative rate of 2.6% was found, all lesions being benign. It appears to be more reliable than the paper disc method but the differences do not reach statistical significance. The FHH test is recommended for screening the general population over the age of 40 years, with rescreening annually.

Australia↗
PubMed1988

Hormonal alterations in the lactating dairy cow in response to thermal stress.

The influence of acute exposure to thermal stress on the secretion of progesterone, estradiol, cortisol, and LH was monitored in 14 lactating Holstein cows. Eight cows were maintained throughout the summer in a refrigerated air-conditioned tie stall barn. An additional eight cows were maintained in outdoor corrals with access only to shade. Rectal temperatures and respiration rates of cows under heat stress conditions were elevated above the cows maintained under air conditioning. Cows in both environments exhibited similar serum concentrations of progesterone and estradiol throughout the estrous cycle. Serum cortisol concentrations were higher in heat-stressed cows compared to cows maintained under cooling. The number of LH pulses on d 5 of the estrous cycle was greatly reduced in the heat-stressed cows compared to the cows under cooling. No differences in the number of pulses of LH were observed on d 12 of the estrous cycle between cows in the two environments. Data suggest that heat stress can suppress anterior pituitary release of LH without having a measurable influence on ovarian steroid hormone secretion.

Animals↗
PubMed1988

Controlling anterior tibial displacement under static load: a comparison of two braces.

This article presents data comparing the restraining effect of the Lenox Hill and the CTi brace to static loading using the KT-1000 Knee Ligament Arthrometer. Testing was performed at 25 degrees and 90 degrees in 15 patients with documented single ligament injuries involving the anterior cruciate. The opposite knee was determined to be normal by subjective and objective testing and was used as the control. Results showed that the anterior drawer tests, both the Lenox Hill and the CTi brace improved the ACL deficient knee significantly. With 15 lb of passive loading, both the Lenox Hill and the CTi brace improved the drawer to within normal limits. However, only the CTi brace was able to return the drawer to within the normal range at the 20 lb force level. Neither brace improved the drawer to normal when subjected to the higher loads created by an active drawer test. At 90 degrees, 15 lb of passive loading could not discriminate between the braced and the unbraced knee or between the normal and ACL deficient knee. When 20 lb of force was applied, only the CTi brace improved the drawer significantly, which placed the drawer into the normal range. Under static testing condition, the CTi brace proved to be better than the Lenox Hill in controlling the anterior drawer in flexion and at 20 lb of passive loads; however, when higher loading forces were used in the active anterior drawer test, neither brace was effective in controlling anterior tibial translation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Patient biodistribution of intraperitoneally administered yttrium-90-labeled antibody.

Although 90Y is one of the best radionuclides for radioimmunotherapeutic applications, the lack of gamma rays in its decay complicates the estimation of radiation dose since its biodistribution cannot be accurately determined by external imaging. A limited clinical trial has been conducted with tracer doses (1 mCi) of 90Y in five patients who then received second-look surgery such that tissue samples were obtained for accurate radioactivity quantitation by in vitro counting. The anti-ovarian antibody OC-125 as the F(ab')2 fragment was coupled with diethylenetriaminepentaacetic acid, radiolabeled with 90Y and administered intraperitoneally to patients with suspected or documented ovarian cancer. Size exclusion and ion exchange high performance liquid chromatography analysis of patient ascitic fluid and serum samples showed no evidence of radiolabel instability although a high molecular weight species (presumably immune complex) was observed in three patients. Total urinary excretion of radioactivity prior to surgery averaged 7% of the administered radioactivity while at surgery the mean organ accumulation was 8% of the administered radioactivity in serum, 10% in liver, 7% in bone marrow, and 19% in bone with large patient to patient variation. The mean tumor/normal tissue radioactivity ratio varied between 3 and 25. On the assumption that the above radioactivity levels were achieved immediately following administration, that the radioactivity remained in situ until decayed and that the dimensions of tumor were sufficient to completely attenuate the emissions of 90Y, the dose to tumor for a 1-mCi administration would be approximately 50 rad with normal tissues receiving approximately 8 rad.

Animals↗
PubMed1987

Influence of blood lead on the ability and attainment of children in Edinburgh.

The effect of blood-lead on children's ability and attainment was investigated in a sample of 855 boys and girls aged 6-9 years from eighteen primary schools within a defined area of central Edinburgh. The geometric mean blood-lead value was 10.4 micrograms/dl. In a stratified subsample, 501 children completed individual tests of cognitive ability and educational attainment from the British Ability Scales (BAS). An extensive home interview with a parent was also done. Multiple regression analyses showed a significant negative relation between log blood-lead and BAS combined score, number skills, and word reading when thirty-three possible confounding variables were taken into account. There was a dose-response relation between blood-lead and test scores, with no evidence of a threshold. The size of the effect was small compared with that of other factors. Lead at low levels of exposure probably has a small harmful effect on the performance of children in ability and attainment tests.

Achievement↗