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Biomedical subjects

C Mason

Publications and source records attributed to C Mason.

At least 19 recordsLinked to original sources
PubMed1992

Naturally acquired CD8+ cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.

In rodent malaria model systems, protective immunity induced by immunization with irradiated sporozoites is eliminated by in vivo depletion of CD8+ T cells, and adoptive transfer of CTL clones against the circumsporozoite protein protects against malaria. We recently demonstrated that volunteers immunized with irradiated Plasmodium falciparum sporozoites produce CTL against peptide 368-390 of the P. falciparum circumsporozoite protein. To determine whether natural exposure to malaria induced similar CTL, we studied 11 adult, male, life-long residents of a highly malarious area of Kenya, who were selected because their lymphocytes had been shown to proliferate after stimulation with peptides 361-380, 371-390, or 368-390 and because nine had been resistant to malaria in previous studies. In four of the 11 individuals there was peptide-specific, genetically restricted, CTL activity. In all four individuals, this activity was unaffected by depletion of CD4+ T cells. In three volunteers the activity was eliminated or reduced by depletion of CD8+ T cells; in the fourth volunteer the CD8+ T cell depletion was uninterpretable. This first demonstration of CD8+ T cell, genetically restricted, Ag-specific CTL against a malaria protein among individuals exposed to endemic malaria provides a foundation for studying the relationship between circulating CTL and resistance to malaria infection.

Amino Acid Sequence↗
PubMed1992

Non-attendance at out-patient clinics: a case study.

Non-attendance at out-patient clinics is a persistent, worldwide problem. In contrast with previous research, a qualitative approach was used in this study to examine reasons for non-attendance at out-patient clinics in one Belfast hospital, by exploring perspectives of general practitioners (GPs), hospital staff and defaulters. Findings revealed conflicts of opinion between GPs and hospital staff on appropriate management of certain medical and postnatal patients. Patients' reasons for defaulting were wide-ranging; however, 32% of those interviewed did not attend, or were recorded as non-attenders, for reasons relating to inefficient hospital administration. It is concluded that the causes of non-attendance were multifactorial, and non-attenders could not be stereotyped as irresponsible. Suggested measures to alleviate the problem include discussion between groups of professionals on responsibility for care of medical and postnatal patients, increased negotiation between patients and physicians in order to develop agreed programmes of care, and, where possible, a shifting of the onus of responsibility for making and cancelling appointments onto patients.

Conflict, Psychological↗
PubMed1992

Carbon monoxide exposure in blast furnace workers.

This study investigated the occupational exposure to carbon monoxide (CO) of a group of blast furnace workers from an integrated steelworks, compared to a control group having no significant occupational CO exposure from other areas in the same works. The study was undertaken in 1984 at Port Kembla, New South Wales. Carboxyhaemoglobin (COHb) levels before and after an eight-hour work shift were measured in 98 male steelworkers: 52 from two CO-exposed iron blast furnaces and 46 controls from production areas in the same steelworks. The sample was stratified by smoking habits. Environmental air CO levels had been found to be consistently higher on one furnace than on the other. Absorption of CO from the working environment occurred in workers on the blast furnace with higher CO levels, regardless of smoking habits. On this blast furnace, some readings of COHb levels after a workshift in nonsmokers approached the proposed Australian occupational limit of 5 per cent COHb saturation. Overall, workers with the highest occupational exposure who smoked most heavily had the highest absorption of CO over a work shift. Biological monitoring gives an accurate measure of individual worker 'dose' of CO from all sources. Both environmental monitoring and biological monitoring need to be included as part of a program for controlling occupational CO exposure.

Breath Tests↗
PubMed1991

Triazolobenzo- and triazolothienodiazepines as potent antagonists of platelet activating factor.

A series of [1,2,4]triazolo[4,3-alpha][1,4]benzodiazepines bearing an ethynyl functionality at the 8-position and the isosteric thieno[3,2-f][1,2,4]triazolo[4,3-alpha][1,4]diazepines were prepared and evaluated as antagonists of platelet activating factor. The effects of substitution were explored in in vitro and in vivo test systems designed to measured PAF-antagonistic activity. Results are discussed and compared with previously published data. Many of the compounds had activity superior to WEB 2086, compound 1. In general, the thieno analogues exhibited better oral activity than the corresponding benzodiazepines. The duration of activity upon oral administration was modulated by the substitution on the acetylenic side chain. Compounds 71 and 81 were selected for further pharmacological evaluation as a result of their good oral potency and exceptionally long duration of action.

Animals↗
PubMed1991

Thienotriazolodiazepines as platelet-activating factor antagonists. Steric limitations for the substituent in position 2.

The preparations of thienotriazolodiazepines bearing a substituted ethynyl group at the 2-position, and the corresponding cis-olefins and fully saturated analogues are described. The compounds were evaluated as potential antagonists of platelet-activating factor (PAF) in in vitro and in vitro test models. The new thienotriazolodiazepines are compared with known related compounds such as WEB 2086 (compound 6) and the phenylethyl derivatives 27 and 28.

Animals↗
PubMed1991

Epstein-Barr virus infection acquired from a cadaveric renal transplant.

A 42-year-old man, seronegative for Epstein-Barr virus (EBV), received a cadaveric renal transplant. Serology from the 27-year-old male donor indicated an active EBV infection. Following treatment for acute rejection with OKT3 the recipient developed a severe systemic illness. Clinical features strongly suggested an acute EBV infection and serology showed seroconversion for EBV. The patient died and autopsy histology revealed widespread polymorphic lymphocyte infiltration in lymph nodes and solid organs. To our knowledge this is the first report of a kidney being transplanted from a donor who was subsequently shown to have had EBV infection at the time of organ retrieval. The EBV status of an organ donor should be considered more frequently.

Adult↗
PubMed1991

Project 2000: a critical review.

Project 2000 forms an example of nurses bringing about change proactively to make nurse education appropriate to the social, technological and medical advances of the second part of the twentieth century. Unexpected problems, however, are emerging as Project 2000 is implemented. It is argued in this article that these problems arise from a failure on the part of the United Kingdom Central Council in 1983 to anticipate the enormous changes that the health service is currently undergoing and a failure, therefore, to make connections between these changes and the educational and organisational changes involved in the implementation of Project 2000.

Education, Nursing↗
PubMed1990

Women as mothers in northern Ireland and Jamaica: a critique of the transcultural nursing movement.

Participant observation and structured interviews with selected groups of mothers in Northern Ireland and Jamaica revealed a variety of individual experiences that highlighted contrasts between the two cultures, and differences within each culture. The findings are used to illustrate the danger of cultural stereotyping, and the implications for the transcultural nursing movement are discussed.

Adolescent↗
PubMed1990

Analysis of the fowlpox virus genome region corresponding to the vaccinia virus D6 to A1 region: location of, and variation in, non-essential genes in poxviruses.

The DNA sequence of the fowlpox virus genome corresponding to the vaccinia virus D6 to A1 region has been determined. Translation of this sequence reveals fowlpoxvirus gene homologues corresponding to the D6, D7, D9, D10, D11, D12, D13 and A1 genes of vaccinia virus. In contrast, no gene homologue for the non-essential vaccinia virus D8 gene was present in fowlpox virus. Instead, a gene transcribed from the opposite strand to the vaccinia virus D8 gene showing no homology to any previously sequenced poxvirus gene was present. The amino terminus of the fowlpox virus D9 homologue had undergone substantial changes, including frameshifts which would be predicted to inactivate the gene. Insertion of a gene cartridge composed of the vaccinia virus p7.5 promoter and the lacZ gene into the fowlpox virus D8, D9 and D10 genes in vitro, followed by recombination into fowlpox virus, was carried out. Stable insertion mutants with the correct genotype were obtained for D8 and D9 which, when tested in chickens did not appear to have been attenuated. No stable insertion mutants were obtained for D10, indicating that this gene probably encodes a function which is essential for virus replication. The D8 and D9 genes of fowlpox virus represent useful insertion sites for the construction of recombinant fowlpox virus vaccines.

Amino Acid Sequence↗
PubMed1990

A 39,000 Mr immunodominant protein of fowlpox virus contains multiple copies of a 12 amino acid repeat sequence.

The nucleotide sequence of an unusual fowlpox virus gene which maps immediately upstream from the fowlpox virus 4b gene has been determined. The 34,000 Mr protein predicted to be encoded by the gene contains 11 copies of a 12 amino acid serine-rich repeat sequence. The seven amino-terminal copies of the repeat sequence are perfectly conserved but variation exists in the four carboxy-terminal copies. Three peptides were synthesized which contained either one copy of the repeat sequence, two copies of the repeat sequence or a hydrophilic amino-terminal region of the protein. All three peptides when injected with adjuvant into rabbits gave rise to antibodies which reacted strongly on Western blots of purified fowlpox virus proteins with a 39,000 Mr protein. When directly compared in Western blots the antipeptide sera were shown to recognize a protein comigrating with one of the two immunodominant proteins recognized by chicken anti-fowlpox virus sera taken 2 weeks post-infection. The virion protein is removed by treatment with sodium deoxycholate suggesting that it is located at or near the surface of the virus.

Amino Acid Sequence↗
PubMed1990

Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission.

Eighty-seven consecutive children and young adults with acute nonlymphocytic leukemia (ANLL) were treated uniformly with induction chemotherapy based on daunorubicin and cytarabine (ara-C), with the addition of etoposide (VP-16) and azacytidine (5-Az) for refractory patients. Of the 65 patients who entered complete remission, 42 were eligible for assessment of response to intensive chemotherapy consisting of four pairs of drugs administered in sequential fashion. Nineteen others with available histocompatibility locus antigen (HLA)-compatible donors were assigned to receive allogeneic bone marrow transplants within 16 weeks from their dates of complete remission. Durations of continuous complete remission (CCR) in the two groups were not significantly different at a median follow-up time of 6 years (P = .30 by log-rank analysis). Kaplan-Meier estimates of CCR probabilities (+/- SE) at 6 years were 43% +/- 13% (transplantation) and 31% +/- 7% (sequential chemotherapy). Postremission failures in the sequential chemotherapy group resulted from bone marrow relapse in 23 of 29 patients (79%), whereas in the transplantation group, failures were equally divided between marrow relapse and transplantation-related complications of graft-versus-host disease (GVHD) or infection due to the immunosuppressive effects of ablative chemotherapy. Comparison of hematologic remission curves indicated a significant advantage for marrow transplantation in terms of systemic leukemia control (P = .06). Thus, in programs of intensive chemotherapy of the type described here, allogeneic marrow transplantation should be seriously considered as alternative therapy for patients in first remission who have an HLA-matched sibling donor, provided that effective methods for control of transplant-related complications are available.

Adolescent↗
PubMed1989

Human lymphocyte proliferative response to a sporozoite T cell epitope correlates with resistance to falciparum malaria.

To identify vaccine relevant T cell epitopes on the circumsporozoite (CS) protein of Plasmodium falciparum, the lymphocyte proliferative responses to 10 CS protein derived peptides were studied in 28 adult Kenyans, and correlated with resistance to malaria. Eight peptides, six of which were not overlapping, induced proliferation of lymphocytes from one to five volunteers, suggesting either genetic restriction of response to each of the T epitopes, or dominance of some T sites on the immunizing sporozoites. The 28 volunteers were radically cured of malaria and during the next 126 days 25 of the 28 were reinfected. Resistance to malaria was not correlated with antibodies to malaria Ag, but was significantly correlated with lymphocyte responses to CS protein residues 361-380 and 371-390. Among the 25 volunteers who became re-infected with malaria, lymphocytes from only two responded to a peptide including residues 361-380 of the P. falciparum CS protein, and only one to peptide 371-390. In contrast, lymphocytes from all three volunteers who did not become infected responded to peptide 361-380 (p = 0.003), and lymphocytes from two of the three responded to peptide 371-390 (p = 0.023). The significant correlation between proliferation to peptides 361-380 and 371-390 and resistance to malaria suggests that at least one epitope within these overlapping peptides is involved in a protective cellular immune response. The data support inclusion of these residues in future CS protein vaccines.

Adult↗
PubMed1989

Effective reinduction therapy for childhood acute nonlymphoid leukemia using simultaneous continuous infusions of teniposide and amsacrine.

The combination of teniposide (VM-26) and amsacrine (AMSA) was evaluated in a dose-finding and efficacy study in 58 patients with relapsed or refractory acute leukemia. Both agents were given as simultaneous continuous infusions for 72 h through separate i.v. lines. All patients were evaluable for toxicity and 57 were evaluable for response; only 2 of 20 with acute lymphoblastic leukemia (ALL), acute mixed-lineage leukemia, or chronic myelogenous leukemia in blast crisis achieved a complete remission (CR). More encouraging was a second-remission rate of 43% (13 complete and 3 partial) in the 37 patients with acute nonlymphoid leukemia (ANLL). Responses occurred only in patients who received VM-26 doses of greater than or equal to 200 mg/m2 per day and AMSA doses of greater than or equal to 100 mg/m2 per day. Thus, the CR rate for relapsed ANLL patients who received the higher doses of both agents was 40% (13 of 33). All responders had previously received epipodophyllotoxin therapy and 40% had also received AMSA. All but one patient had severe leukopenia (less than 2.0 x 10(9) leukocytes/l) and thrombocytopenia (less than 50.0 x 10(9) platelets/l) as a results of therapy. Severe mucositis (grade 3 or 4) was the dose-limiting toxicity. Our results indicate that VM-26 plus AMSA, given by continuous infusion, is effective in the treatment of ANLL. Further phase II studies should consider using VM-26 at 200 mg/m2 per day and AMSA at 100 mg/m2 per day, but the best administration schedule remains unclear.

Adolescent↗
PubMed1989

Hereditary white sponge naevus.

The authors report two cases of white sponge naevus in the same family, where the condition had clearly been inherited by the daughter from her mother. The positive family history aided correct diagnosis of this entirely benign lesion.

Adult↗