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Biomedical subjects

R Harris

Publications and source records attributed to R Harris.

At least 379 records · Page 21Linked to original sources

Clinical and immunogenetic studies in multicase rheumatoid families.

We have studied HLA haplotypes, autoimmune diseases and circulating autoantibodies in 23 families with multiple cases of rheumatoid arthritis; 76 per cent of rheumatoid arthritis and 70 per cent of non-rheumatoid individuals were positive for HLA-DR4. The haplotypes Bw44-Bf*S-DR4; B40-Bf*S-DR4; and B15-Bf*S-DR4 were found in 13, 9 and 7 per cent of probands respectively and the B15-Bf*S-DR4 haplotype was found between four and five times more frequently in DR4-positive rheumatoid arthritis than in DR4 positive, non-rheumatoid arthritis families. Rheumatoid arthritis segregated with a DR4 positive haplotype in 13 families and with a DR4 negative haplotype in seven. Analysis of HLA haplotype sharing showed greater than random sharing by affected siblings which is in keeping with genes within the MHS influencing susceptibility to rheumatoid arthritis. Autoimmune thyroid disorders were seen in 8 per cent of family members investigated. They were significantly more frequent in those families in which rheumatoid arthritis segregated with a non-DR4 bearing HLA haplotype. This suggests that genes for autoimmune thyroid disease might predispose to rheumatoid arthritis independently of DR4. These genes are probably not HLA-linked, as there was no trend for HLA haplotype sharing to be increased in sibling pairs with either rheumatoid arthritis and thyroid disease or rheumatoid arthritis and thyroid autoantibodies respectively.

Adolescent↗

Enterobronchial fistula.

Enterobronchial fistula is a rare condition. The authors describe a 47-year-old man who had a fistula between the small bowel and tracheobronchial tree, 8 years after resection of an adrenal carcinoma. The report illustrates the difficulties in diagnosis and the surgical treatment. In particular, the use of hyperosmolar, water-soluble contrast medium in radiologic investigations is to be avoided and the use of a double-lumen endotracheal tube is mandatory if a general anesthetic must be given. Despite its rarity, enterobronchial fistula can be diagnosed through a carefully taken history, confirmed safely by roentgenography and cured surgically.

Bronchial Fistula↗

The complete nucleotide sequence of the major adult beta globin gene of Xenopus laevis.

We present the complete nucleotide sequence of the major beta globin gene of Xenopus laevis with 127 nucleotides of sequence upstream of the gene and 212 nucleotides downstream. The start point of transcription was determined by S1 mapping and primer extension and the site of polyadenylation by comparison with the mRNA sequence determined from a cDNA clone. Comparison of the X. laevis sequence with other genes transcribed by RNA polymerase II reveals conserved features in the 5' flanking, 5' noncoding, intron/exon boundary, and 3' noncoding regions.

Amino Acid Sequence↗

Investigation of the organisation of the major proteins in bovine myelin membranes. Use of chemical probes and bifunctional crosslinking reagents.

Bovine myelin was incubated with a variety of bifunctional reagents and chemical probes. The use of a photosensitive hydrophobic compound, 1-azido-[125I]iodobenzene, led to the suggestion that the proteolipid protein is deeply intercalated into the hydrophobic milieu of the membrane, but did not support the contention that regions of the basic protein behave in a similar fashion. Crosslinking studies indicated that both polypeptides may be present in the membrane as homodimers and these dimers may be part of much larger assemblies. These results give rise to a somewhat different model for the structural organisation of myelin to that proposed earlier.

Animals↗

The nucleotide sequence of the mRNA encoding a tadpole beta-globin polypeptide of Xenopus laevis.

We have determined the nucleotide sequence of a cloned cDNA derived from the mRNA encoding an abundant Xenopus laevis tadpole beta-globin polypeptide. The cloned sequence contains the entire coding region of the mRNA as well as most of its 5'- and 3' -noncoding regions. The complete amino acid sequence of the protein has been deduced. Comparison of this sequence with that of the major adult beta-globin polypeptide of X. laevis shows that the two gene products are highly diverged from each other, the tadpole sequence actually displaying a somewhat greater homology to the human beta-like globin sequences than to the adult frog sequence. An unusual feature of the predicted tadpole beta-globin polypeptide is the presence of a phenylalanine residue at its carboxyl terminus. All known amphibian, avian, and mammalian beta-globin polypeptides have a COOH-terminal histidine residue, and this amino acid is known to play a major role in the alkaline Bohr effect. This observation suggests that, as has been found for two fish hemoglobins which also have a COOH-terminal phenylalanine residue, the tadpole hemoglobin of X. laevis will display a much reduced alkaline Bohr effect.

Amino Acid Sequence↗

Further experience of vitamin supplementation for prevention of neural tube defect recurrences.

In accordance with a previous protocol, a second cohort of 254 mothers with a history of previous neural tube defect (NTD) births was before a subsequent conception and continued until the time of the second missed menstrual period. There were 2 NTD recurrences (0.9% of 234 infants/fetuses examined), which is significantly fewer than the 11 NTD recurrences (5.1% of 215 infants/fetuses examined) born to 219 unsupplemented (US) mothers in the same centres over the same period. When the data for the two cohorts were combined, the overall recurrence rates were 0.7% for 454 fully supplemented (FS) mothers and 4.7% for 519 US mothers. The recurrence rates after 1 previous NTD were 0.5% for FS and 4.2% for US mothers: after 2 or more previous NTDs, 2.3% for FS and 9.6% for US. There were no recurrences among the offspring of a further 114 mothers whose duration of supplementation fell short of the full regimen (partially supplemented, PS).

Female↗

Simplified preparation of rabbit Fab fragments.

Papain attached to solid-phase CH-Sepharose 4B was used to digest rabbit IgG. Protein A-Sepharose CL-4B was used to remove undigested IgG and Fc fragments. Pure Fab fragments free of IgG, Fc fragments and papain were readily obtained by this procedure with a yield of about 75%. Polyacrylamide gel electrophoresis of the Fab in the presence of sodium dodecyl sulphate gave a single band under both reducing and non-reducing conditions. The molecular weight of the Fab determined by sedimentation equilibrium was 49,200. Unlike the IgG, the Fab obtained did not form precipitin lines when used in immunoelectrophoresis.

Animals↗

Complete nucleotide sequence of a cloned cDNA derived from the major adult alpha-globin mRNA of X. laevis.

The complete sequence of a cloned cDNA derived from the major adult alpha-globin mRNA of Xenopus laevis (the South African Clawed Toad) is presented. The sequence contains the complete coding and 3' non-coding regions of the mRNA and part of the 5' non-coding region. The amino acid sequence of the encoded alpha-globin polypeptide has been deduced and is compared to other alpha-globin polypeptides. We find that the sequence is equally diverged from a bullfrog tadpole alpha-globin polypeptide and human alpha-globin polypeptide suggesting that these three sequences may have diverged from a common ancestral sequence several hundred million years ago.

Amino Acid Sequence↗

Ocular Candida with pale-centered hemorrhages.

A 54-year-old man with severe thermal burns had Candida corneal ulcers and Candida septicemia develop, and he died 39 days after admission to the hospital. At autopsy examination, fungi were noted in the cornea to extend across the intact Descemet's membrane and were also found within foci of retinitis and choroiditis. Also, hemorrhages (some of which had pale centers) were present in both retinas. Histopathologic examination of these hemorrhages disclosed that the pale centers were comprised of a disrupted small blood vessel surrounded by an acellular material that most likely represented fibrin-platelet aggregates.

Candida↗

An HLA-DR negative acute leukaemia which stimulates MLC and CMC responses.

We describe an acute myelomonocytic leukaemia (E72) devoid of cell-surface HLA-DR antigens, but capable of inducing cellular responses. Leukaemia E72 induced proliferation of normal lymphocytes in primary mixed lymphocyte culture (MLC), which was only weakly inhibited by anti-DR sera. Depletion of a small percentage (congruent to 4%) of DR+ cells on a cell-sorter failed to abrogate the capacity of E72 to stimulate MLC and cell-mediated cytotoxicity (CMC) responses. We found that normal lymphocytes primed with E72 responded in secondary MLC to lymphocytes and leukaemias, suggesting that the lymphocyte-activating determinant (LAD) on E72 is not leukaemia-specific. In addition, E72 induced CMC responses to both leukaemias and lymphocytes. We suggest that E72 may express a novel HLA or non-HLA LAD.

Aged↗

Clearance rates and systemic effects of intravenously administered interleukin 2 (IL-2) containing preparations in human subjects.

The present study was designed to examine the feasibility of in vivo administration of interleukin 2 (IL-2) to induce cytotoxic cell activity against tumours in human subjects. IL-2 was prepared from blood leukocytes stimulated with phytohaemagglutinin (PHA) and partially purified by membrane chromatography to exclude PHA. Administration of different amounts of IL-2 in vivo to 2 patients with melanoma revealed that the initial level of IL-2 in the circulation was related to the dose given and had a half-life of approximately 22.5 minutes. The initial and subsequent levels of IL-2 were lower than that expected to occur from equilibration in plasma and extracellular fluid. This was not apparently due to inactivation by serum factors because fresh human serum had little effect in vitro on the induction of mitogenic or cytotoxic activity by IL-2. Spontaneous division of lymphocytes was increased following IL-2 administration and it is suggested that clearance of IL-2 in vivo may reflect, in part, absorption by activated lymphocytes in the circulation. Side effects noted shortly after administration of the partially-purified IL-2 preparations included transient pyrexia, hypoglycaemia, increased cortisol levels, lymphocytopenia and signs of mild intravascular coagulation. No long-term effects were noted. These initial results suggest that systemic injection of purified preparations of II-2 may be a feasible approach to induce cytotoxic T cells in vivo.

Adult↗

Distribution and turnover rate of acetylcholine receptors throughout the junction folds at a vertebrate neuromuscular junction.

The distribution and turnover rate of acetylcholine receptors labeled with 125I-alpha-bungarotoxin were examined in innervated mouse sternomastoid muscle by electron microscope autoradiography using the "mask" analysis procedure. We compared the total population of receptors with receptors newly inserted at the junction 2 d after inactivation with nonradioactive alpha-bungarotoxin, both at the top (thickened) region of the postjunctional folds (pjm) and the nonthickened bottom folds. We found that the receptor site density was approximately 10 times greater on the thickened pjm than on the nonthickened bottom folds for both total and newly inserted receptors. This ratio does not change significantly during a 6-d period after labeling the new receptors. Furthermore, calculated values for turnover time of receptors show that both total and newly inserted receptors at both regions of the junctional folds have half-lives for degradation within the range given in the literature for slow junctional receptors. These data exclude a simple migration model whereby receptors are preferentially inserted in the nonthickened region of the junctional folds and then migrate into the thickened membrane at a rate equal to the turnover rate of the receptors.

Animals↗

Isolation and growth of a Pseudomonas species that utilizes cyanide as a source of nitrogen.

A simple method of isolating bacteria that utilize cyanide as a source of nitrogen for growth has been developed. This involved supplying hydrogen cyanide as a vapour to glucose-containing minimal-salts agar plates. The bacteria isolated were Gram-negative, oxidase-positive rods producing a fluorescent green pigment and were tentatively identified as strains of Pseudomonas fluorescens. Three organisms were studied further and shown to be P. fluorescens biotype II. One of these (NCIB 11764) was grown in a glucose-containing fed-batch culture with either NH4Cl or KCN as the limiting nutrient. Cyanide-grown bacteria produced stoichiometric amounts of ammonia from cyanide when pulsed with cyanide under aerobic conditions. Stimulation of oxygen uptake was seen on addition of cyanide to suspensions of cyanide-grown but not ammonia-grown bacteria.

Ammonium Chloride↗