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Biomedical subjects

M Griffiths

Publications and source records attributed to M Griffiths.

At least 19 recordsLinked to original sources
PubMed1996

Characterization of the antigenic structure of human type II collagen.

A series of 101 peptides each 20 amino acids in length (10-residue overlap) spanning the helical portion of the mature alpha-chain of human type II collagen (CII) was synthesized. DBA/1 (H-2q) mice were immunized with individual peptides, and draining lymph node cells were challenged in vitro. Strong responses were measured to three peptides: peptide I (residues 74-93), peptide 14 (residues 254-273), and peptide 81 (residues 924-943). B10.Q (H-2q) mice were responsive to peptides I and 81 but not to peptide 14. B10.RIII (H-2r) mice, which are resistant to arthritis induction following immunization with human CII, were unresponsive to peptides I, 14, and 81. Using single amino acid truncated peptides, we determined minimal immunostimulatory lengths for peptides I and 81. Residues critical to antigenicity were identified by introducing alanine and glycine substitutions into minimal length immunostimulatory peptides. The determinants within peptides I and 81 are 100% homologous to mouse CII and are autoantigens. Peptide 81 has homology to viral proteins. Peptide 14 is 90% homologous to mouse CII and has homology to heat shock proteins.

Adjuvants, Immunologic↗
PubMed1996

Molecular biology of APO E alleles in Alzheimer's and non-Alzheimer's dementias.

Current research into the aetiology of the dementias is focused upon genetic factors which give rise to the disease process. Recently the Apolipoprotein E gene (APO E) and in particular the epsilon 4 allele has been shown to be a risk factor for late onset Alzheimer's disease (AD) where there is an increased frequency of the epsilon 4 allele. The epsilon 4 allele has also been shown to reduce the age at onset of dementia in AD in a dose dependent manner, with the epsilon 2 allele having an opposing effect. We have genotyped a large series of clinically and neuropathologically confirmed cases of AD and found the expected increase in the Apolipoprotein epsilon 4 allele frequency when compared to a control population. Similarly, in Lewy Body Dementia (LBD) an increased epsilon 4 frequency is also found though a normal epsilon 2 frequency exists, unlike in AD where the epsilon 2 frequency is reduced. No changes in APO E allele frequencies were found in presenile AD, Parkinson's disease with or without dementia, or in Down's syndrome. No association was found between any of the APO E alleles and the histopathological indices of AD, cortical senile plaques and neurofibrillary tangles, in any disease category. Neurochemical indicators of AD, loss of choline acetyltransferase activity was also unaffected by APO E genotype. Whilst their appears to be a strong association between the APO E allele and AD and also in LBD, other related neurodegenerative disorders associated with dementia do not show such a linkage. Changes in the epsilon 2 allele frequency may indicate a genetic difference between AD and LBD. The epsilon 4 allele does not appear to influence the burden of AD type pathology and this is particularly relevant given the relative lack of NFT in LBD indicating that factors other than SP or NFT may govern the onset of dementia.

Alleles↗
PubMed1995

The role of the cholinergic system in the development of the human cerebellum.

High affinity (-)nicotine ([3H]nicotine), alpha-bungarotoxin ([125I]alpha-bungarotoxin) and muscarinic binding ([3H]N-methyl scopolamine) in the human cerebellum were compared between the foetal period (23-39 weeks gestation) and young adulthood (14-34 years) in an autoradiographic study. To estimate proportions of muscarinic receptor subtypes variable wash times and displacement with pirenzepine were employed. [3H]Nicotine binding and total muscarinic binding in foetuses exceeded that in young adults by a factor of 6 and 2 respectively in the dentate nucleus, and by a factor of 3 in white matter. [3H]Nicotine and muscarinic binding was also higher in the foetal external granule cell layer than in the internal granule cell layer of adult, [125I]alpha-Bungarotoxin binding was raised in the dentate nucleus of the foetus compared with the adult. The M2 subtype appeared to be the predominant muscarinic receptor in the cerebellum, however it tended to represent a lower proportion of the muscarinic binding in the foetus than the adult. All 3 receptor types were highest in the foetal brainstem where the M3 + M4 muscarinic subtypes appeared to predominate. The p75 nerve growth factor receptor, measured by immunocytochemistry, in common with cholinergic receptors, paralleled choline acetyltransferase activity which has previously been reported to be high in the cerebellum during late foetal development and to fall in adulthood.

Acetylcholine↗
PubMed1995

Glomerulonephritis after human parvovirus infection in homozygous sickle-cell disease.

Glomerulonephritis with proteinuria of sufficient degree to manifest the nephrotic syndrome followed aplastic crises induced by human parvovirus (B19) in seven patients with homozygous sickle-cell disease, within 7 days in five patients and 6-7 weeks in two. Segmental proliferative glomerulonephritis was found in all four patients who underwent acute renal biopsies and focal segmental glomerulosclerosis was found in the fifth patient who had a biopsy 4 months later. One patient recovered completely, one died in chronic renal failure after 3 months, and the others had impaired creatinine clearance, four with continuing proteinuria.

Adolescent↗
PubMed1995

A microprocessor based photoplethysmograph for use in clinical practice.

A microprocessor-based system of photoplethysmography and its use in measuring skin blood flow is described. The system was designed specifically for use over long periods and for the analysis of the output to be handled by a personal computer. The photoplethysmograph described in this paper is shown to be a qualitative method for assessment of changes in peripheral skin blood flow. There is potential for use of this instrument in a variety of clinical conditions.

Adult↗
PubMed1995

Diurnal variation of sex hormone binding globulin and insulin-like growth factor binding protein-1 in women with polycystic ovary syndrome.

OBJECTIVES: The aim of this study was to examine (1) the diurnal variation in SHBG and (2) the inter-relationships of insulin, IGF-I, SHBG and IGFBP-1 over 24 hours in 10 women with anovulatory PCOS and compare them with weight-matched ovulatory controls. PATIENTS AND METHODS: The two groups comprised 10 anovulatory women with PCOS (as defined by clinical, ultrasound and biochemical criteria) and 10 weight matched controls. Serum samples were taken at two-hourly intervals for 24 hours and stored for measurement of SHBG, IGFBP-1, insulin and IGF-I. Differences between the groups were compared using the Wilcoxon ranked paired tests of the individual peak and trough concentrations in each group. The variation in insulin, IGFBP-1 and SHBG concentrations over 24 hours was tested using two-way analysis of variance with the factors time and subject. Spearman's correlation coefficient was calculated from the subjects' median value over 24 hours. RESULTS: The median (interquartile range) body mass index (BMI) was 25.2 (22.2-29.3) in the PCOS group and 24.3 (23.2-25.7) kg/m2 in the control group. Serum testosterone (T) and LH levels were significantly raised in the PCOS group compared to the control group; T 3.8 (2.9-5.6) vs 1.9 (1.9-2.5) nmol/l (P < 0.007) and LH 12 (10-15) vs 4.1 (3.6-4.5) IU/I (P < 0.005) respectively. There was no diurnal variation in SHBG. The median (interquartile ranges) of the peak SHBG concentrations was lower in the PCOS group: 29.4 (14.9-39.4) vs 52.1 (39.4-61) nmol/l in the control group (P < 0.01). The fasting levels of insulin at 0600 h (median (interquartile ranges)) were not significantly different between the groups; 6.6 (5.4-9.8) and 6.2 (1.9-7.6) mU/l, respectively, although the peak median concentrations were significantly different; PCOS 66.1 (50.9-129.2) vs 40 (36.1-74.2) mU/l (P < 0.05). Two-way analysis of variance showed a diurnal variation in insulin concentrations in the control group (P = 0.001) but not in the PCOS group (P = 0.1). The diurnal variation in IGFBP-1 was similar in the two groups but the peak median levels were lower in the women with PCOS 54.9 (22.3-79.2) vs 71.5 (60.5-99.3) micrograms/l (P < 0.03). The decline in IGFBP-1 concentrations correlated with the increase in insulin concentrations. The IGF-I concentrations were similar in the two groups. There was a significant negative correlation between SHBG and insulin (P < 0.05) and between insulin and IGFBP-1 (P < 0.01). CONCLUSION: This study demonstrates that there is no diurnal variation in SHBG concentrations and confirms the finding of a marked diurnal variation in the concentration of IGFBP-1. Women with PCOS who are anovulatory have an abnormal pattern of insulin secretion with an absence of diurnal variation compared to weight matched controls. This provides further evidence of the relative insulin resistance which is independent of weight found in women with anovulatory PCOS. The inverse correlations of insulin concentrations with SHBG and IGFBP-1 support the role of insulin as a possible regulator of the circulating levels of these binding proteins although the difference in the time course of their response makes it unlikely that they are co-regulated.

Circadian Rhythm↗
PubMed1995

Sexual knowledge interview schedule: reliability.

The Sexual Knowledge Interview Schedule (SKIS) is a 46-item interview schedule with an abuse scale and knowledge scale. The knowledge scale includes feelings, body parts identification, body parts function and general sexual knowledge. The reliability of the SKIS is reported. Internal consistency for scales/subscales ranges from 0.78 to 0.96. Inter-rater reliability was 95.3% agreement and test-retest reliability was 70.1%.

Adolescent↗