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Biomedical subjects

C Hawkins

Publications and source records attributed to C Hawkins.

At least 19 recordsLinked to original sources
PubMed1991

The effect of a chimeric mouse-human CD7 antibody on human T, natural killer, and lymphokine-activated killer cell activity in vitro.

A chimeric CD7 antibody has been constructed with mouse variable and human constant regions and is currently being assessed in the prophylaxis of renal graft rejection. In this study we have investigated if this antibody or its murine parental form inhibits the function of a number of immune effector mechanisms involved in host defense against infection and/or malignancy. Most memory T cells and all natural killer cells express the CD7 antigen and could therefore be affected by CD7 antibody. Murine and chimeric CD7 antibodies significantly inhibit the alloproliferation of naive (65 +/- 4% and 66 +/- 8%, respectively) but not memory T cells (86 +/- 2% and 98 +/- 4%, respectively) in a primary mixed lymphocyte reaction relative to the negative control CD10 antibody (P less than 0.001). The memory T cell proliferative response to recall antigen is also largely unaffected by murine and chimeric CD7 antibodies relative to the negative control antibody (91 +/- 12% and 103 +/- 10%, respectively). The CD7 antigen is almost completely modulated from the surface of NK cells after incubation for 24 hr with either the murine or chimeric CD7, but not the CD10, negative control. The modulation of CD7 antigen by antibody, however, does not affect the cytotoxic function of either the NK or lymphokine-activated killer cells significantly. Preincubation with the chimeric antibody however, consistently showed a small inhibition relative to the negative control of 75-80% in NK assays and to 80-90% in LAK assays. These data suggest that both murine and chimeric CD7 antibodies may have a selective effect on alloproliferation but may largely spare a major component of the host's innate immunity as well as memory T cell proliferation to previously encountered antigens.

Antibodies↗
PubMed1990

The bistratenes: new cytotoxic marine macrolides which induce some properties indicative of differentiation in HL-60 cells.

The biological effects of cytotoxic macrolide polyethers, the bistratenes, isolated from the ascidian Lissoclinum bistratum, have been examined. Bistratene A was toxic to HL-60 human promyelocytic leukemia cells with an IC50 value of 424 nM. At lower concentrations (10-100 nM), bistratene A induced the incomplete differentiation of these cells along the monocyte/macrophage pathway. These effects were not due to inhibition of DNA synthesis. Bistratene B had similar effects to bistratene A. At micromolar concentrations these compounds enhance the phospholipid-dependent activity of type II protein kinase C from bovine spleen. The bistratenes provide new probes for studying the molecular mechanisms governing cell growth and differentiation.

Acetamides↗
PubMed1989

Measles outbreak among unvaccinated preschool-aged children: opportunities missed by health care providers to administer measles vaccine.

A measles outbreak in an inner-city area primarily involved preschool-aged children younger than 5 years of age. The reasons why 31 unvaccinated preschool children with measles disease had not been vaccinated were investigated. For some patients, health care providers missed opportunities to vaccinate eligible patients against measles. Of the 26 patients whose full immunization status was known, ten (38%) were vaccinated with diphtheria and tetanus toxoids and pertussis vaccine and/or oral poliovirus vaccine at a time when they could have received measles vaccine simultaneously, according to recommendations of the Immunization Practices Advisory Committee and the American Academy of Pediatrics. In addition, five of ten health care providers interviewed missed at least one opportunity to administer measles vaccine because of a minor illness that was not a contraindication to vaccination. Unvaccinated patients were more likely to receive health care in the public sector, have single mothers, and have parents who had no knowledge of existing vaccines; they were less likely to be age-appropriately immunized with other antigens. If measles immunization levels among preschool children in the United States are to be increased, education of both health care providers and parents, coupled with innovative strategies targeted to preschool children, particularly of low socioeconomic groups in inner cities, are needed.

Adolescent↗
PubMed1988

A "back door" approach to analysis of ethanol-associated risks and behavior.

Ethanol has been detected in the majority of medical examiner cases involving nonnatural death and in a substantial number of natural deaths. The higher the serum alcohol concentration (SAC), the greater were the odds that death was due to external (traumatic) causes. We identified 149 medical examiner cases that were positive for ethanol and negative for 11 major drug of abuse groups, and studied those cases to further clarify ethanol-related risk factors and behaviors. Based on terms of frequency of occurrence, the data identify SACs of 201 mg% to 300 mg% as a particularly high risk factor for sudden, unexpected, traumatic death. Traumatic deaths associated with SACs below 100 mg% were infrequent, and attendant opinions concerning the contributory role of ethanol must be made with circumspection. SACs below 150 mg% could not be used to predict whether or not the decedents had been engaged in active or sedentary behavior prior to death because both situations occurred with equal frequency. At SACs between 151 mg% and 350 mg%, active situations were observed three times as often as sedentary situations. When SACs were 350 mg%, sedentary situations were observed twice as often as active situations. Suicide victims and driver fatalities rarely showed SACs above 350 mg%; therefore finding such SACs in apparent suicidal or driver fatality situations should prompt a thorough investigation to rule out other possibilities.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗
PubMed1987

Medicolegal audit in the West Midlands region: analysis of 100 cases.

One hundred medicolegal cases were analysed to obtain quantitative data about diagnoses and the causes of litigation that affect hospital doctors in the National Health Service. Sixteen actions concerned minor problems that are an unavoidable risk of treatment, and 39 were due to natural causes. In other cases it was debatable whether a medical accident or negligence was responsible. At the end of three years 73 actions had been withdrawn, 12 settled out of court, and one lost in court by the plaintiff, and 14 were pending. Of these 14, nine were likely to reach court on charges of negligence. Contributory causes were failure of communication in 27 and matters connected with the patient's attitude or personality in 20. Because much time and money are spent on cases that should never have started a doctor should sit on the legal aid panel to give advice for medical cases. Also, solicitors should obtain an independent medical opinion when a complaint is first received from a patient. Consent forms should be more informative and give details of what can reasonably be expected from treatment and its possible risks.

England↗
PubMed1987

Inhibited drinking and pica in rats following 2-deoxy-D-glucose.

A sequence of studies sought to determine if 2-deoxy-D-glucose (2DG) produces malaise as a side effect. Drug treatment at dosages at least as low as 250 mg/kg triggered an immediate inhibition of fluid intake. In nondeprived animals, 750 mg/kg but not lower dosages of 2DG evoked a delayed but statistically significant level of pica as measured by kaolin consumption. Twenty-four hour food deprivation failed to produce pica, and previous claims that kaolin intake is a specific index of gastrointestinal distress therefore received additional support. Thirsty rats injected with 750 mg/kg 2DG displayed a delayed pattern of pica largely similar to that previously observed with undeprived subjects; although, under optimal circumstances, significant increases in kaolin consumption may be evident as soon as one hour post-injection. In general, these data indicated that malaise may be an important influence of 2DG; but dosage and time course parameters associated with post-drug reductions in drinking suggested that a separable consummatory inhibition effect may also occur.

Animals↗
PubMed1987

Genetic variation in mitochondrial DNA from some aboriginal Australians.

Mitochondrial (mt) DNAs from 17 aboriginal Australians, predominantly from the coastal region of the Northern Territory were isolated and digested with four four-base restriction endonucleases, two of which revealed variation between samples. The observed fragment patterns were used directly in parsimony analyses of phylogenetic relationships between the samples, and were also converted to estimates of the number of substitutions per nucleotide position between samples (delta), which estimates were then used in distance analyses of phylogeny. The inferred fragment patterns of the completely sequenced 'Cambridge' human mtDNA were also included in these analyses. No strong evidence of geographic variation was found, consistent with previous findings of Australian aborigines and other humans generally, although the most divergent sample was one of two from Sydney, indicating that further work is desirable. The estimate of mean difference between samples (diversity), 0.0017 +/- 0.0003 (mean +/- 95% confidence interval), is significantly lower than that reported previously for humans generally.

Australia↗
PubMed1986

Response variability of human brain tumors to AZQ in tissue culture.

In a series of 28 glioma-derived cell cultures and 6 non-gliomatous CNS tumors, AZQ has been found to have varying degrees of growth inhibiting or cytotoxic activity in nearly all lines tested at doses greater than 100 mcg/ml. At dose levels comparable to the clinically achieved levels (1 mcg/ml), AZQ was found to have a cytotoxic effect in 8 of 28 glioma-derived and 2 of 6 non-gliomatous cell lines tested. These findings suggest that AZQ has activity against certain glioma-derived cells in culture at a response ratio similar to that seen in vivo. There, appear to be significant differences in the degree of responsiveness in different patients' tumor cells which can be detected in vitro prior to clinical treatment.

Antineoplastic Agents↗
PubMed1986

Intake of a liquid diet after 2-deoxy-D-glucose injections in rats.

The effects of a liquid diet after 2-deoxy-D-glucose (2DG) were examined following water deprivation, after food deprivation, and at longer post-injection intervals when animals reportedly are hypophagic as a function of drug treatment. Water deprived rats were unable to increase their post-drug feeding when ingesting the liquid diet; and in food deprived subjects, intake patterns of liquid diet and of lab chow pellets were essentially identical after 2DG. The tendency of a 750 mg/kg dosage to produce a longer-term hypophagic reaction was more evident in animals given pellets instead of the liquid diet. While previous studies have found the liquid diet to promote 2DG-induced feeding in lesioned subjects, the present data demonstrate that such facilitation effects do not invariably occur during post-drug conditions in which animals are inhibited in their intake.

Animals↗