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Biomedical subjects

M Griffiths

Publications and source records attributed to M Griffiths.

At least 73 records · Page 4Linked to original sources

Mouse cytomegalovirus is infectious for rats and alters lymphocyte subsets and spleen cell proliferation.

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.

Animals

Occurrence of autoimmune diseases and autoantibodies in multicase rheumatoid arthritis families.

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.

Arthritis, Rheumatoid

Diagnosis and treatment of chlamydial infections.

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.

Adult

Intake of milk by suckling echidnas (Tachyglossus aculeatus).

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.

Aging

Isolation of a gene enhancer within an amplified inverted duplication after "expression selection".

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.

Animals

Association of MHC antigens with susceptibility to and severity of rheumatoid arthritis in multicase families.

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.

Adult

An assessment of the value of electron microscopy in tumour diagnosis.

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.

Humans

Obesity in boys: the distinction between fatness and heaviness.

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.

Age Factors

An immunohistological study of secondary Sjögren's syndrome.

The labial biopsies from 13 patients with secondary Sjögren's syndrome (SS) and four disease controls were examined with a panel of monoclonal antibodies to human leucocyte antigens. Large numbers of T cells were found in most of the biopsies. In seven SS patients the T helper/inducer subset was found to be predominant. Antibody to HLA class I antigens consistently stained leucocytes, but other cell types stained more variably. Although the staining with antibody to HLA class II antigen was often weak, approximately as many cells stained with this antibody as with an antileucocyte antibody, implying that the T cells were activated. Anti-IgD revealed membrane staining of a corona of IgD-positive cells in structures resembling germinal centres. Isolated cells throughout the sections also showed strong cytoplasmic staining with anti-IgD. These results suggest a role for T-cell-dependent local antibody synthesis in the pathogenesis of the disease.

Adult

Carbohydrates of the milk of the platypus.

Twelve samples of milk of the platypus, Ornithorhynchus anatinus, had a mean content of 3 X 3% hexose. Of this, almost half was L-fucose. Of the total monosaccharides present in acid hydrolysates of the water-soluble carbohydrates, L-fucose constituted 33%, D-galactose 29%, glucosamine 20%, D-glucose 11% and sialic acid 7%. Free lactose was found in only trace amounts. In all samples, the major oligosaccharide was difucosyllactose, which represented 39-52% of the total hexose. Five higher neutral oligosaccharides (from penta- to nonasaccharides) were isolated and their monosaccharide compositions determined. Each contained one or more residues of fucose, glucosamine and galactose and one residue of glucose. The presence in the milk of 4-O-acetyl-N-acetylneuraminlactose was detected by thin-layer chromatography. All milk samples examined contained protein material (probably glycoprotein), which was not precipitated by chloroform-methanol extraction. No evidence was obtained for quantitative or qualitative changes in carbohydrates during the course of the lactation season except for a small decline in total hexose towards the end of the season.

Animals

Intestinal glycosidase activities in one adult and two suckling echidnas: absence of a neutral lactase (beta-D-galactosidase).

The activities of various glycosidases in homogenates of the small-intestinal mucosa of one adult and two suckling echidnas, Tachyglossus aculeatus, were investigated. The activities of lactase (beta-D-galactosidase), beta-N-acetylglucosaminidase, neuraminidase and alpha-L-fucosidase were higher in the sucklings than in the adult animal. Maltase and isomaltase activities were lower. Sucrase and cellobiase activities were absent or present in trace amounts only. The lactase activity had a pH optimum of 4.0-4.5, was predominantly in the soluble fraction following ultracentrifugation and was inhibited by p-chloromercuribenzene sulfonate, suggesting that it was due to a lysosomal acid beta-galactosidase and not a brush-border neutral lactase. The maltase activity of the sucklings also had the characteristics predominantly of a lysosomal acid hydrolase. It is proposed that in suckling echidnas, the oligosaccharides (mainly neuraminyllactose and fucosyllactose) of the mother's milk are digested intracellularly by lysosomal enzymes, rather than at the brush border, of the epithelial cells of the small-intestinal mucosa.

Animals

Qualitative and quantitative changes in milk fat during lactation in the tammar wallaby (Macropus eugenii).

There are major quantitative and qualitative changes in the milk lipids during lactation in the tammar wallaby, Macropus eugenii. The crude lipid content of the milk is relatively low during the first 10 weeks of lactation; between 10 and 26 weeks post partum the lipid content increases gradually but after that it increases rapidly. The triglyceride fraction of the lipid at early stages of lactation contains a large amount of palmitic acid and relatively little oleic acid whereas mature milk exhibits little palmitic and much oleic acid. In the early stages of lactation fat represents 15% of the total solids and carbohydrate 55%; around 26-30 weeks post partum the carbohydrate moiety falls sharply to a level less than 2% of the solids while lipids increase to c. 60% of the solids. These changes coincide with increases in milk solids, emergence of the young from the pouch, ingestion of herbage, and fermentation of cellulose in the stomach.

Animals

Isolation of cellular DNA sequences that allow expression of adjacent genes.

We have employed a strategy for the isolation and identification of cellular control (expression) sequences dependent on their ability to confer expression on a selectable gene devoid of its own expression sequences. The polyoma virus (Py) Hae II-BamHI DNA fragment, which comprises 84% of the intact viral DNA and contains the Py transforming region but lacks Py 5' expression sequences, was decreased markedly in its transformation of rat cells. Hae II-cleaved mouse cellular DNA was ligated to the Py Hae II-BamHI fragment. A transformed colony (H1) isolated after transfection of the ligated DNA onto rat cells was found to contain multiple inserts of Py DNA, most of which were biologically inactive. A transformed colony (H2) isolated after transfection of rat cells with total H1 DNA was found to contain a single insert of Py DNA. The H2 cells are highly tumorigenic and synthesize the three Py tumor antigens. Initiation of transcription of the Py early mRNAs in H2 cells occurs at the same Py nucleotides as in complete Py DNA. The viral and adjacent cellular DNA sequences were cloned from H2 cellular DNA. The transforming efficiency of the cloned Py transforming region and adjacent H2 cellular DNA was 20-40% of that of the viral DNA containing Py expression sequences. By BAL-31 deletion mapping it was observed that the first 58 base pairs of H2 cellular DNA were sufficient for the expression of the Py-transforming region. The sequence of the first 149 base pairs of the H2 cellular DNA was determined and does not show any striking similarities to upstream 5' sequences of a number of viral and host structural genes. Features of the H2 cellular sequence are discussed.

Base Sequence