'Use of general anaesthesia and sedation in the GDS in East Anglia'.
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Biomedical subjects
Publications and source records attributed to M Griffiths.
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Labial biopsy specimens from eight patients with primary Sjögren's syndrome (SS), 10 patients with secondary SS, and three healthy controls were studied with monoclonal antibodies identifying HLA class I and class II antigens; interferon-alpha, beta, and gamma; interleukin 2 (IL2); and the IL2 receptor (Tac) among others. In the normal biopsy specimens there was evidence of HLA class I and, to a lesser extent, class II antigens in both ducts and acini, though this was much less marked than in the Sjögren's biopsy specimens. Interferon-gamma staining, but not interferon-alpha or beta, was also considerably enhanced in the biopsy specimens from the patients with Sjögren's syndrome. These data support the view that in Sjögren's syndrome the release of interferon-gamma may be involved in the induction of class II determinants. Our observations were broadly similar in both primary and secondary Sjögren's syndrome except that patients with primary Sjögren's syndrome tended to have more diffusely scattered T lymphocytes.
This study compared 7-d energy intakes of 37 young children at low (Group N) and high (Group O) risk of subsequent obesity, as judged from parental obesity. The energy intake of Group O was 16 per cent lower than Group N (P = 0.02). Although the intakes of all the children considered together and also Group N children alone showed the usual wide variability and absence of correlation with body size, the intakes of Group O children were significantly correlated with their weight and height (r = 0.5). The results confirm a previous study and suggest that, since basal metabolic rate and body weight are known to be correlated, attention should be focused on differences in expenditure in investigations of the aetiology of childhood obesity.
The MES-1 element was previously isolated from restricted total mouse cellular DNA by "expression selection"--the ability to reactivate expression of a test gene devoid of its 5' enhancer sequences. Mes-1 has been tested in long-term transformation and short-term CAT expression assays. In both assays MES-1 is active independent of orientation and at a distance when placed 5' to the test gene. The element is active with heterologous promoters and functions efficiently in both rat and mouse cells. MES-1 activates expression by increasing transcription from the test gene's own start (cap) site. Thus the expression selection technique can be used for the isolation of DNA sequences with enhancer-like properties from total cellular DNA.
Seventy-one lung carcinomas from 66 different patients were stained with a panel of monoclonal antibodies. Twenty-nine were small cell lung carcinoma (SCLC), 15 adenocarcinomas, 17 squamous carcinomas and 10 large cell carcinomas. Three of the monoclonal antibodies recognize different cytokeratins, three recognize other epithelial antigens and one recognizes a neural antigen. Both formalin-fixed and cryopreserved tumours were studied using an indirect immunoperoxidase method. 23/29 SCLC reacted with all but one of the antibodies which recognize epithelial antigens. This staining was similar to that seen in non small cell lung carcinomas (NSCLC) and provides further evidence that SCLC are true epithelial tumours. All but one of the SCLC stained with the antibody recognizing a neural antigen. This antibody did not stain squamous or adenocarcinomas. However, four of the large cell carcinomas stained well with this antibody, suggesting that SCLC and some large cell carcinomas share a common pathway of differentiation. There were variations of staining seen both within and between tumours. This has obvious implications if immunotargetting with monoclonal antibodies is to be used diagnostically or therapeutically.
The Smith strain of mouse cytomegalovirus (MCMV) was infectious for infant and mature DA strain laboratory rats as judged by development of neutralizing antibodies and specific spleen cell proliferation on stimulation with MCMV antigen. An i.p. inoculum of 10(6) PFU of MCMV was fatal for more than two-thirds of infant mice (1-7 days of age), and disseminated viral infection was documented by isolation of virus from body organs. In contrast, weanling and adult rats did not become ill as a result of infection with a larger inoculum of 10(7) PFU. However, these older MCMV infected rats did show transient reversals of T helper/suppressor cell ratios and alterations of immune cell function as detected by in vitro spleen cell proliferation assays. Seven days after MCMV infection, there was a generalized increase in 3H-thymidine incorporation by spleen cells in both resting (unstimulated) cultures and cultures exposed to mitogens (Con A, PHA, LPS) and to MCMV antigen. At 14 days, the spleen cell proliferation in the unstimulated cultures returned to normal but was depressed compared to controls in response to Con A. These observations show that laboratory rats are susceptible to MCMV infection and that asymptomatic infection may occur and cause transient alterations in lymphocyte subsets and in their reactivity to mitogens.
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The presence of autoimmune diseases and autoantibodies has been studied in 237 individuals from 17 families with two or more members affected by rheumatoid arthritis (RA). Hyperthyroidism occurred significantly more frequently than in a local control population (p less than 0.05), but if the RA cases were excluded this significance was lost. Thyroid cytoplasmic and microsomal antibodies were significantly more common (p less than 0.001), and this remained true if RA sufferers were excluded (p less than 0.01). The prevalence of both clinical thyroid disease and circulating thyroid autoantibodies was similar in the families where RA was associated with HLA-DR4 and in those where no DR4 association was observed. RA and immune thyroid disease may, therefore, share a common inherited factor, but this is unlikely to be at the HLA-DR locus. Antinuclear factor (ANF) was found in association with RA and with HLA-DR3 within the RA group (p less than 0.02). Relatives of RA sufferers did not show any excess of ANF positivity. The prevalence of pernicious anaemia (PA) and gastric parietal cell antibody did not differ from the expected.
A patient with Klinefelter's syndrome and diabetes mellitus was diagnosed as having myelodysplasia. Cytogenetic analysis of the peripheral blood and the bone marrow cells confirmed the presence of a constitutional 47,XXY chromosome complement. In addition, complex karyotypic abnormalities were present.
The major chlamydial infections are conjunctivitis and pneumonia in infants and urethritis, cervicitis, salpingitis and ocular infection in adults. Tetracyclines are usually the drugs of choice for the treatment of chlamydial infections. Erythromycin therapy is preferred for pregnant women and for neonates with conjunctivitis. Follow-up examination and treatment of sexual partners are required for the control of chlamydial infections.
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Estimation of milk intake in the sucklings of three captive echnidnas, Tachyglossus aculeatus, and in one living in its natural habitat were made by determination of sodium turnover rate and sodium content of the milk. The mean rate of sodium influx of the sucklings was 2.48 +/- 1.31 mmol/kg X day. The daily rates of milk consumption and growth rates were variable with a mean weight increment of 0.41 +/- 0.10 g for each ml of milk consumed. There is a wide disparity in growth rates of echidna young that is related to differences in the body weights of the mothers.
We have attempted to isolate and identify cellular expression sequences from F9 teratocarcinoma DNA by utilizing their ability to reactivate a selectable gene devoid of its own expression sequences (expression selection). Restriction nuclease-digested F9 cellular DNA was ligated to a polyoma virus (Py) DNA fragment which contains an intact transforming region but is incapable of inducing transformation because it lacks the viral 5' enhancer sequence. The ligation mixture was used to transfect Rat-1 cells and a transformed cell line, 3B, was isolated. The 3B cell line contained a single type of Py DNA insert, which was molecularly cloned as an 18-kilobase BglII fragment. A weak cellular enhancer was identified in a 4.7-kilobase BamHI fragment upstream from the Py sequences. Both the Py DNA and the enhancer sequences were found to be present in an inverted duplication in the 3B clone. The presence of this structure in 3B genomic DNA was confirmed by the analysis of selectively isolated inverted duplicated sequences, and the structure was found to be at least 22 kilobases long. In the 3B cell line, the inverted duplicated sequences containing the Py and enhancer sequences are quite stable and are amplified 20- to 40-fold. The strongly transformed phenotype of the 3B cells may be a result of this amplification. The formation of inverted duplications as a part of the amplification mechanism as well as a general strategy for the cloning of inverted duplicated (amplified) sequences is discussed.
A study of HLA association with rheumatoid arthritis (RA) in multicase families has been performed in north east England. Two hundred and nineteen individuals from 13 families were assessed for the presence of RA, and all were HLA typed. Thirty-nine were found to have classical or definite RA by American Rheumatism Association (ARA) criteria. Thirty-five (90%) of these possess HLA-DR4, confirming the previously reported association of RA with DR4. A further 19 individuals were found to have probable RA or gave a convincing history of previous inflammatory polyarthritis. Thirteen (68%) of these possess HLA-DR4, and this is not significantly different from non-affected family members of whom 63% possess DR4. These results suggest that HLA-DR4 is associated only with the more severe forms of RA. Homozygosity for HLA-DR4 was not associated with either earlier onset or more severe disease when compared with heterozygous DR4. Possession of the haplotype most commonly inherited with the RA in individual families was not associated with earlier onset but may be associated with more severe disease. The severity of RA appears to be influenced by the major histocompatibility complex (MHC) in these families.
The contribution of electron microscopy to the diagnosis of tumours in a general hospital has been investigated. During a three year period 235 cases were examined, of which 66 (28%) were diagnostic problems by light microscopy. In 42 (64%) of the problem cases a contribution towards diagnosis was made by ultrastructural examination, which was most useful for anaplastic polygonal cell tumours, of some value for spindle cell neoplasms, and least helpful in the further categorisation of metastatic carcinoma.
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An anthropometric survey of approximately 2350 boys aged 1-8 years was conducted as part of a study of pre-school child growth. It was shown that there was no close relationship between obesity measured as fatness from the triceps skinfold and the development of heaviness as judged by weight-for-height. It is suggested that the study of obesity in children should involve classification into sub-groups identifiable as the heavy but not fat, the fat but not heavy and those who are both heavy and fat. This may help in understanding the nature of obesity and its implications in future disease.