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Biomedical subjects

R Hill

Publications and source records attributed to R Hill.

At least 19 recordsLinked to original sources
PubMed1992

Karyotypic and phenotypic changes during in vitro aging of human endothelial cells.

Karyotypic and phenotypic changes were found in human adult endothelial cells (EC) during aging in vitro. A trisomy of chromosome 11 was found in 11 out of 12 EC cultures examined, derived from 9 cell lines from 8 donors. The incidence of this trisomy in some cell lines increased over time from 0% to as much as 100% near the end of their in vitro life span. A number of oncogenes and other important genes are on chromosome 11. These genes might play a role in the changes observed. An increase in the percentage of polyploid cells was also found near the end of the in vitro life span in 6 lines. The cellular levels of two gene products characteristic of the EC, von Willebrand factor (vWF) or Factor VIII, and angiotensin converting enzyme (ACE) were also monitored. vWf was studied in 2 lines and was decreased in both with serial passage. ACE decreased in three out of the four lines examined. These chromosomal and phenotypic changes which occur with increasing age in vitro make the endothelial cell a suitable model to study in vitro culture-related changes, senescence, cardiovascular disease, and tumorigenesis.

Adult↗
PubMed1992

Synaptic potentials and transfer functions of lamprey spinal neurons.

1. Electrotonic and chemical synaptic potentials were measured as a function of frequency of presynaptic action potentials. Over the frequency range from 0.02 to 10 Hz, the electrotonic synaptic potential was constant, while the chemical synaptic potential decreased in magnitude. Above 10 Hz, both synaptic events decreased in magnitude consistent with filtering by the dendritic structures. 2. Electrotonic synaptic transfer functions from 0.5 to 100 Hz were measured for the I1 reticulospinal Müller axon to spinal neuron electrotonic synaptic junction of the lamprey spinal cord using paired recordings from the pre-synaptic terminals and the post-synaptic neurons. In addition to this two-point synaptic transfer function, individual single point impedance functions of both the post-synaptic soma and the pre-synaptic axon terminal were measured. 3. The measured functions were interpreted with a computational model based on a three dimensional reconstruction of a Lucifer yellow filled motoneuron. Simulations of the model for a synaptic location of the I1 synapse were consistent with the measured synaptic transfer functions. 4. Synaptic potentials were simulated for inputs on dendrites near the I1 axon as well as distal dendritic regions. The high frequency filtering increased as the synaptic location was moved from the soma to the periphery, but the potential response on distal dendrites was larger than would have been predicted from the end of the equivalent cylinder of a Rall model that was used to fit soma impedance functions. 5. Electrotonic post-synaptic potentials were enhanced by the activation of a TTX-sensitive negative conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Evaluation in mental health services: some quality assurance models.

This paper examines the context in which a concern for evaluation in mental health services has emerged. Quality assurance activities are seen as the main method of evaluating such services at the present time. A distinction is made between internal and external approaches to quality assurance and an example of each method is examined for its strengths and weaknesses. Successful quality assurance programmes are seen as being dependent on an amalgamation of these two approaches and two generic systems which adopt this method, "QUARTZ" and "Psychiatric Monitor" are considered for their strengths and weaknesses. It is suggested that evaluation strategies should be assessed for their capacity to promote organizational change. The increasing influence of the User movement is discussed.

Humans↗
PubMed1992

Apamin blocks the slow AHP in lamprey and delays termination of locomotor bursts.

The effects of apamin on the slow afterhyperpolarization (sAHP) in spinal neurones and on the frequency of rhythmic bursting during fictive locomotion were investigated in the lamprey spinal cord in vitro. Apamin, which is a selective blocker of a small conductance KCa channel responsible for the sAHP in many types of neurones, was also found to reduce the sAHP in lamprey neurones. The summation of the sAHP is considered to be an important burst terminating factor in the spinal locomotor network and thereby to regulate the frequency of fictive locomotion. In support of this view, apamin was found to reduce the frequency of rhythmic bursting during fictive locomotion induced by kainate and NMDA. Serotonin, which has previously been shown to reduce the sAHP and slow the rate of rhythmic bursting, may therefore act, at least in part, on apamin-sensitive KCa channels.

Action Potentials↗
PubMed1992

Expression of a missense mutation in the messenger RNA for beta-myosin heavy chain in myocardial tissue in hypertrophic cardiomyopathy.

We have determined that a missense mutation in exon 13 of the beta-myosin heavy chain (beta MHC) gene is expressed in the messenger RNA (mRNA) isolated from a right ventricular endomyocardial biopsy obtained from the proband of a family with hypertrophic cardiomyopathy. The mutation is the result of a substitution of an adenine for a guanine residue in one allele of the beta MHC gene and creates a second recognition site for the restriction endonuclease Ddel in exon 13. The mutation is inherited in a Mendelian fashion and co-segregates with hypertrophic cardiomyopathy in this family. Complementary DNAs synthesized from RNA isolated from the endomyocardial biopsy were cloned into a plasmid vector and sequenced to confirm the expression of both the normal and mutant allele in mRNA of myocardial tissue. This is the first report of the transcription of a mutant beta MHC gene allele into mRNA of the myocardium.

Base Sequence↗
PubMed1992

Detection of a new mutation in the beta-myosin heavy chain gene in an individual with hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant disease affecting primarily the myocardium. The gene responsible for FHCM has been localized to chromosome 14 in some families and several mutations have been described in the beta-myosin heavy chain (beta MHC), a candidate gene for the disease. We recently identified a family with HCM in whom we did not detect any of the known mutations in the beta MHC gene (the alpha/beta MHC hybrid gene and the missense mutation in exons 13 and 9). However, we did observe a novel 9.5-kb BamHI restriction fragment length polymorphism detected by a beta MHC probe on Southern blots of DNA from the proband of this family. Similarly, a novel 3.8-kb TaqI polymorphism and a novel 4.3-kb HindIII polymorphism were detected on Southern blots of DNA from the same proband. Polymerase chain reaction (PCR) was used to amplify the segment of the beta MHC that was detected by pSC14 probe. PCR amplification of the distal 3'-end of the beta MHC gene yielded an additional product in the DNA template from the proband which was subsequently cloned and sequenced. The sequence analysis showed a 2.4-kb nucleotide deletion involving one allele of the beta MHC gene. The deletion includes part of the intron 39, exon 40 including the 3'-untranslated region and the polyadenylation signal, and part of the beta-alpha MHC intergenic region. This deletion was inherited in Mendelian fashion in an additional three members of this small family of which only the proband has developed clinically diagnosed HCM at a very late onset (age 59 yr), the other three family members are younger and have not developed the disease at the ages of 10, 32, and 33 yr.

Aged↗
PubMed1991

Can morbidity associated with untreated asthma in primary school children be reduced?: a controlled intervention study.

OBJECTIVE: To determine whether an intervention programme based on existing school and community resources can reduce school absence and improve participation in games lessons and sport in children with unrecognised or undertreated asthma. DESIGN: Parallel group controlled intervention study. SETTING: 102 primary schools in Nottingham: 49 were randomised to receive the intervention and 53 to be control schools. SUBJECTS: All children aged 5 to 10 years with parent reported absence from school because of wheezing in the previous year and taking no treatment or beta agonists only. INTERVENTIONS: Children with asthma were referred to their general practitioner for assessment of symptoms and treatment. Teachers were given education on asthma by the school nurse in 44 of the 49 intervention schools. MAIN OUTCOME MEASURES: Changes in school absence and missed games and swimming lessons because of wheezing, and schools' policy towards management of asthma in school. RESULTS: Of 17,432 children screened, 451 met the entry criteria--228 in intervention schools and 223 in control schools. 152 (67%) children in intervention schools visited their general practitioner, of whom 39 (26%) were given a new diagnosis of asthma and 58 (38%) had treatment for asthma increased or changed. Over the next academic year mean (SE) parent reported school absence due to wheezing fell significantly, but to a similar extent, in both intervention and control schools (0.82 (0.11) and 1.09 (0.21) weeks respectively). There was little change in school recorded absence or participation in games lessons and swimming lessons in either group. At the end of the study intervention schools were more likely to have improved aspects of management of asthma in school. CONCLUSION: The intervention resulted in a majority of children being assessed by their general practitioner and improved teachers' understanding and management of asthma, but it did not result in any appreciable reduction in morbidity.

Absenteeism↗
PubMed1991

Nucleotide sequence analysis of three cDNAs coding for Poa p IX isoallergens of Kentucky bluegrass pollen.

Grass pollen allergens are one of the major causes of type I allergic reactions (allergic rhinoconjunctivitis, allergic bronchial asthma, and hayfever) in temperate climates afflicting 15-20% of a genetically predisposed population. Workers have found considerable physico- and immunochemical heterogeneity within the grass pollen allergens which has made them difficult to purify for both therapeutic uses and further biochemical study. We recently reported the construction of a cDNA library in lambda gt11 using mRNA extracted from dehydrated Kentucky bluegrass (KBG, Poa pratensis). Here, we present the nucleotide and deduced amino acid sequences for three KBG pollen allergen cDNA clones, KBG 41, 60, and 31, which were isolated from the above library using a pool of six sera from grass pollen allergic patients. These clones exhibit an exceptionally high degree of sequence similarity to one another, only minor similarity to other known allergens, and no homologies to other known proteins or genes. The predicted molecular mass for the cloned proteins range from 28.3 to 37.8 kDa with pI values of 9.6-10.2. All three clones appear to possess leader peptides and lack asparagine sequons required for N-glycosylation. Therefore, the molecular mass of the post-translationally modified proteins were calculated to be 28.4-34.9 kDa, which is consistent with the size of the polypeptides revealed in Western blots of pollen proteins using an antiserum to a recombinant peptide encoded by the partial cDNA clone KBG 8.3. Northern blotting analysis indicates that expression of the genes corresponding to these clones is confined to pollen tissue. The results suggest that the clones code for a group of proteins that represent a new and previously uncharacterized group of grass pollen isoallergens, which have been hereby designated as Poa p IX.

Allergens↗
PubMed1991

Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.

We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays. Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale. Plaque density contributed only 26% of that strength.

Aged↗
PubMed1991

Clinical improvement in parkinsonian patients undergoing adrenal to caudate transplantation is not reflected by chromogranin A or basic fibroblast growth factor in ventricular fluid.

Fifteen patients with Parkinson's disease underwent open transplantation of autologous adrenal medulla to the caudate nucleus. Motor function was evaluated before and after surgery and was found to be significantly improved at 5-9 months following surgery. Cerebrospinal fluid was taken from the ventricle adjacent to the implant site at the beginning of the operation and at 1 week, 3 months, and 5-9 months following surgery. The cerebrospinal fluid was assayed for chromogranin A (CgA), the major soluble protein in chromaffin granules, and basic fibroblast growth factor (bFGF), a neurotrophic growth factor found in normal brain and adrenal medulla. CgA levels did not increase following surgery, suggesting that a significant number of chromaffin cells did not survive or that surviving chromaffin cells did not secrete a significant amount of CgA. Basic fibroblast growth factor was undetectable in the ventricular cerebrospinal fluid.

Adrenal Medulla↗
PubMed1991

Glass ceramic approach to controlling the properties of a glass-ionomer bone cement.

Glass-ionomer dental cements have potential as bone cements in joint replacement surgery. However, commercially available glasses used in dental cements suffer from the loss of fluorine during the melting procedure and from phase separation of the glass upon quenching, giving rise to inter- and intra-batch variation. A model glass was examined in which minimal loss of fluorine is observed. This results in a glass whose composition is reproducible between batches. This glass will crystallize both above and below the glass transition temperature following heat treatments. Cements can be produced whose properties vary with the degree of crystallinity of the glass-ceramic. A commercial glass was also examined and was found to crystallize to an apatite phase.

Bone Cements↗
PubMed1991

The effect of malnutrition on vaccination against Dermatophilus congolensis infection in ruminants.

Vaccination against Dermatophilus congolensis was carried out in groups of lambs raised on optimal or energy deficient diets. The groups differed significantly in weight, body condition score and plasma total protein and albumin. All animals were then challenged with D. congolensis in a dose response infection model. The vaccine was effective in the well nourished animals, reducing the number of affected lambs in the vaccinated group and the severity of the lesions and increasing the minimum dose required to cause infection. In contrast, all of the vaccinated energy-deficient lambs developed lesions. There was some evidence of vaccine effect in these animals but this was not as marked as that seen in the well nourished lambs. The malnourished lambs, vaccinated and non-vaccinated, took longer to heal than the well nourished groups. Resistance to challenge was not associated with serum antibodies or skin test reactivity to D. congolensis antigens.

Actinomycetales↗
PubMed1991

Hetergeneous tumour response to photodynamic therapy assessed by in vivo localised 31P NMR spectroscopy.

Photodynamic therapy (PDT) is efficacious in the treatment of small malignant lesions when all cells in the tumour receive sufficient drug, oxygen and light to induce a photodynamic effect capable of complete cytotoxicity. In large tumours, only partial effectiveness is observed presumably because of insufficient light penetration into the tissue. The heterogeneity of the metabolic response in mammary tumours following PDT has been followed in vivo using localised phosphorus NMR spectroscopy. Alterations in nucleoside triphosphates (NTP), inorganic phosphate (Pi) and pH within localised regions of the tumour were monitored over 24-48 h following PDT irradiation of the tumour. Reduction of NTP and increases in Pi were observed at 4-6 h after PDT irradiation in all regions of treated tumours. The uppermost regions of the tumours (those nearest the skin surface and exposed to the greatest light fluence) displayed the greatest and most prolonged reduction of NTP and concomitant increase in Pi resulting in necrosis. The metabolite concentrations in tumour regions located towards the base of the tumour returned a near pre-treatment levels by 24-48 h after irradiation. The ability to follow heterogeneous metabolic responses in situ provides one means to assess the degree of metabolic inhibition which subsequently leads to tumour necrosis.

Animals↗