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Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 199 records · Page 11Linked to original sources
PubMed1989

Functional evidence for the recognition of endogenous peptides by autoreactive T cell clones.

The fine specificity of two human T cell clones responding to autologous HLA-DR1 expressing antigen-presenting cells (APC) in the absence of nominal antigen has been investigated using Epstein-Barr virus-transformed B cells (BCL) of known DR beta 1 domain sequence. It was found that responsiveness was markedly affected by changes in a limited number of residues in this domain. Substitution of the DR1 beta sequence at one residue, position 74, even conservatively, was found to be particularly significant. Located on the beta 1 domain alpha-helix, this residue is predicted to point into the antigen-binding groove and is therefore unlikely to make contact with the T cell receptor. This finding suggests that these T cells are specific for a bound endogenous peptide within the autologous major histocompatibility (MHC) binding groove. The autospecific T cell clones also responded to murine L cell transfectants expressing DR alpha DR1 beta as well as to transfectants expressing the mouse/human hybrid MHC molecule I-E alpha DR1 beta but not to the reciprocal combination DR alpha I-E beta, thus confirming the importance of the beta 1 domain to T cell recognition. In contrast to the autocytotoxicity observed with BCL, cytolysis of the murine L cells expressing the HLA-DR1 molecule was slight and only found at high effector-target ratios. In addition, although fixation enhanced the recognition of BCL, capacity of the murine L cells bearing the HLA-DR1 molecule to stimulate T cell clone proliferation was markedly reduced by aldehyde fixation. When taken together, these results suggest that the endogenous peptides recognized by these autoreactive T cells are of human origin.

Amino Acid Sequence↗
PubMed1989

Partial zona dissection of human oocytes when failure of zona pellucida penetration is anticipated.

Partial zona dissection (PZD) of human oocytes facilitates sperm penetration through mechanically made holes in the zona pellucida. Only 1 of 69 eggs was damaged when sucrose was used to shrink the ooplasm during micromanipulation. The fertilization rate of micromanipulated oocytes in 18 couples with male factor infertility was 68% (34/50), which compared favourably with insemination of non-micromanipulated controls (21/45, 47%). PZD was advantageous in oligozoospermic patients, but not in cases of asthenozoospermia, combined semen problems or immunological infertility. Three twin and two singleton pregnancies resulted following replacement of 23 micromanipulated and eight control embryos in 14 patients. No differences in embryo morphology and development rates were found between the micromanipulated and control groups. The incidence of polyspermy in couples with abnormal semen analyses was relatively low (less than 20%) possibly due to partial activation of the oocytes following exposure to sucrose. Polyspermy was high (57%) in normozoospermic patients with either immunological infertility (n = 3) or failure of fertilization in previous cycles (n = 4). In the three immunological patients, nine of 11 hyaluronidase and sucrose-exposed control embryos fertilized and six implanted, possibly indicating that cumulus and corona cells are contributing factors inhibiting fertilization in such cases.

Embryo Transfer↗
PubMed1989

Does 99Tcm human serum albumin alter the characteristics of nebulized pentamidine isethionate?

Nebulized pentamidine has been used as therapy for Pneumocystis carinii pneumonia. The lung dose delivered using different nebulizer systems and doses of pentamidine from 50-600 mg is unknown. To measure this a marker which does not alter the characteristics of the nebulized pentamidine solution must be found. We have assessed the aerosol characteristics of four jet nebulizers (System 22, System 22 Mizer, Optimist, Respigard II) and one ultrasonic device (Pulmosonic) using two concentrations of pentamidine isethionate (50 mg and 300 mg) in 3 ml of solution. The jet nebulizers were operated at a flow rate of 6 l min-1, a rate suitable for home use. These measurements were repeated with 99Tcm labelled human serum albumin (HSA) added to the solutions. A linear relationship between 99Tcm-HSA activity and pentamidine concentration was demonstrated by using a nine stage cascade impactor. The Respigard II and Optimist produced the best results in terms of particle size (96% less than 5 microns), but the addition of the tracer to the latter led to a smaller particle size range and a reduction in the amount of aerosol present at the mouthpiece. The Mizer system had 52% of particles less than 5 microns, the Pulmosonic 46%. The Respigard II had a total output of 8.7 mg for the 50 mg concentration and 30.9 mg for the 300 mg concentration. The System 22 produced corresponding outputs of 18.0 mg and 67.1 mg with 54% of the aerosol particles less than 5 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1989

First trimester maternal serum lysosomal enzymes: implications for carrier testing and prenatal diagnosis.

Carrier detection for lysosomal storage diseases is sometimes possible by evaluating maternal serum levels of specific enzymes. However, lysosomal enzymes (LE) can be modified by maternal hormonal changes in pregnancy or embryonic contributions. Maternal serum was obtained prospectively in the follicular phase and at 2-5 and 7-11 weeks after conception from 13 infertility patients with precisely known ovulation dates. Eleven enzyme activities were determined fluorimetrically using 4-methylumbelliferyl substrates. Using repeated measures ANOVA, alpha-N-acetyl-glucosaminidase (p less than 0.05), hexosaminidase A (p less than 0.005) and hexosaminidase A and B (p less than 0.005) increased during the first trimester, and 8 enzymes did not change significantly. Our data show differing patterns of LE in the first trimester. These may be explained by: (1) variability of maternal reaction to hormonal changes of pregnancy, or (2) variable embryonic contributions suggesting differential ontogeny and placental transfer of these enzymes. The increase in levels of the 3 specific LE in maternal serum may interfere with the accuracy of carrier testing in early pregnancy, but pregnancy should not interfere with the other 8.

Adult↗
PubMed1989

Diurnal variation in TSH and free thyroid hormones in patients on thyroxine replacement.

Eleven patients with treated hypothyroidism were investigated to examine the effects of time on their thyroid function tests. Each patient was clinically and biochemically euthyroid on once daily thyroxine replacement therapy, taken in the morning. TSH followed a diurnal rhythm with a peak level at 23.30 h and a trough level at 14.30 h. Four subjects had TSH trough levels within the normal range, but with peak levels outside this range. FT4 and FT3 levels fell from their highest levels some three hours after ingestion to the lowest levels just prior to the next dose. This study shows that there are significant time-related variabilities in TSH and thyroid hormone levels in treated hypothyroid patients. This should be taken into account when interpreting results of their thyroid function tests.

Aged↗
PubMed1989

Streptococcus faecalis arthritis.

Septic arthritis due to Streptococcus faecalis is rare. We describe a case in which synovial biopsy was required for diagnosis and a new longterm antibiotic combination using ciprofloxacin and amoxicillin was successful in treating the infection. Comparison is made with previous reported cases and the usual poor outcome in this condition.

Amoxicillin↗
PubMed1988

Selection of medical students--effect on class composition of using non-academic criteria.

The attributes of 2,304 applicants for admission to the University of the Witwatersrand Medical School were analysed. Those measured by previous academic performance, biographical history and assessment at interview were significantly different. Inclusion of non-academic criteria in admission decisions broadens the personal attributes of the class, and alters the ethnic and gender composition, without affecting subsequent failure rate.

Educational Measurement↗
PubMed1988

Radiation sensitivity and DNA repair in Caenorhabditis elegans strains with different mean life spans.

The sensitivities to three DNA damaging agents (UV and gamma-radiation, methyl methanesulfonate) were measured in four recombinant inbred (RI) strains of Caenorhabditis elegans with mean life spans ranging from 13 to 30.9 days, as well as in the wild-type strains used to derive these RI's. Sensitivities at several stages in the developmental cycle were tested. There were no significant correlations between mean life span and the lethal effects of these 3 agents. Excision of two UV-radiation-induced DNA photoproducts was also measured. Long-lived strains were no more repair competent than shorter-lived strains. These data indicate that DNA repair plays at best a minor role in the aging process of C. elegans.

Animals↗
PubMed1988

Hepatic stores of retinol and retinyl esters in elderly people.

Post-mortem concentrations of hepatic retinol and retinyl esters were determined in 40 subjects aged over 65 years to assess the effects of disease and malnutrition on vitamin A reserves. Three groups of patients (mean age 79.6 years) were studied: (1) previously healthy, (2) chronically ill, (3) chronically ill and wasted. There was no significant difference in height or age between the groups, but group 3 was lighter than both group 1 (P less than 0.001) and group 2 (P less than 0.05). Free retinol and retinyl esters were measured by high pressure liquid chromatography, and the total hepatic retinol calculated. Analysis of variance showed that the three groups differed significantly (P less than 0.02) with regard to total retinol, retinyl palmitate and total retinyl ester content.

Aged↗
PubMed1988

Effects of tracheostomy breathing on brain and body temperatures in hyperthermic sheep.

1. We measured rectal and hypothalamic temperature in sheep breathing nasally and via a tracheostomy, during hyperthermia resulting from exposure to a hot environment, exercise and fever. 2. In normothermic and hyperthermic sheep hypothalamic temperature was up to 1.0 degree C lower than rectal temperature when the sheep breathed nasally. Tracheostomy breathing abolished the rectal-hypothalamic temperature difference. 3. In sheep breathing via the tracheostomy and exposed to a dry-bulb temperature of 45-50 degrees C for 2 h, hypothalamic temperature exceeded rectal temperature by about 0.4 degrees C, and was significantly higher than that in sheep breathing nasally in the same environment. 4. During exercise on a treadmill and in the post-exercise period, the difference between hypothalamic and rectal temperature was abolished in the sheep while breathing through the tracheostomy, and rectal temperature rose to higher levels compared to those evident in the same activity while breathing nasally. 5. After an I.V. injection of 0.4 micrograms/kg lipopolysaccharide (LPS), the difference between hypothalamic and rectal temperature again was abolished in the sheep when breathing through the tracheostomy, but rectal temperature rose significantly less compared to when breathing nasally. 6. Our results indicate that selective brain cooling depends on upper respiratory tract cooling in normo- and hyperthermic states in sheep.

Animals↗
PubMed1988

Sodium aurothiomalate does not block interleukin 1 production in rabbits.

Gold salts may attenuate inflammatory processes by inhibiting interleukin 1 production. It is shown that sodium aurothiomalate does not act as an antipyretic after intravenous injection of two pyrogens into rabbits. Consequently, it cannot suppress interleukin 1 production, a conclusion confirmed by an in vitro lymphocyte activating factor assay. Chronic sodium aurothiomalate treatment, however, did depress the blood leucocyte count significantly.

Animals↗