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Biomedical subjects

J Holmes

Publications and source records attributed to J Holmes.

At least 109 records · Page 6Linked to original sources
PubMed1989

Multidrug resistance in haemopoietic cell lines, myelodysplastic syndromes and acute myeloblastic leukaemia.

Resistance to cytotoxic agents is a common clinical problem encountered in the treatment of human myelodysplastic syndromes (MDS) and acute myeloblastic leukaemia (AML). Cellular acquisition of the multidrug resistance (MDR) phenotype confers loss of sensitivity to a wide range of structurally dissimilar anti-neoplastic agents. This state can arise through increased expression of the mdrl (P-glycoprotein) gene. We have used the mdrl gene probe to investigate adriamycin resistant (HL60/AR) and vinblastine resistant (CEM/VLB100) human leukaemic cell lines. In addition, peripheral blood or bone marrow cells from 66 patients with MDS and AML have been screened for gene amplification and 40 cases for increased mRNA expression. P-glycoprotein gene amplification was observed only in the (CEM/VLB100) and not in the HL60/AR on any other leukaemic cell line. Gene amplification was not found in any patient's cells. Eighteen out of 40 patients showed an increase (2----20) of mdrl mRNA expression. These results are not only of significance in understanding the biology of human drug resistance but have practical importance in the design of anti-leukaemic therapy.

Blotting, Southern↗
PubMed1988

IL-4 is required to generate and sustain in vivo IgE responses.

Antibodies of the IgE isotype play a predominant role in immediate hypersensitivity reactions. IL-4, a T cell-derived lymphokine that stimulates increased Ia expression by resting B cells and increased IgG1 secretion by LPS-activated B cells in vitro, has also been shown to regulate in vitro and in vivo polyclonal IgE responses. We report that large quantities of a purified anti-IL-4 mAb inhibit primary in vivo polyclonal IgE responses by 99% in mice infected with Nippostrongylus brasiliensis or injected with anti-IgD antibodies, and totally inhibit secondary Ag-specific IgE responses to TNP-keyhole limpet hemocyanin without effect on either IgG1 or IgG2a responses to these stimuli. The lack of effect of anti-IL-4 antibody on IgG1 secretion cannot be explained simply by inadequate neutralization of IL-4, inasmuch as the doses of anti-IL-4 antibody used blocked an N. brasiliensis-induced increase in B cell Ia expression by more than 85%, whereas in vitro studies indicate that enhancement of B cell Ia expression requires less IL-4 than induction of IgG1 secretion. In addition to demonstrating that IL-4 plays a necessary role in the generation of an in vivo IgE response, we show that IL-4 has an important role in sustaining established IgE responses, because anti-IL-4 antibody, when given at the peak of an N. brasiliensis- or TNP-keyhole limpet hemocyanin-induced IgE response, accelerates the declines in total serum IgE and in IgE anti-TNP antibody levels, respectively. These observations suggest that the effects of IL-4 on in vivo immune responses may be more specific than might have been predicted from in vitro observations, and that regulation of IL-4 production or action may be useful for the prevention or therapy of immediate hypersensitivity disorders.

Animals↗
PubMed1988

Supportive analytical psychotherapy. An account of two cases.

Supportive psychotherapy is much practiced, but little described. An account is given of an approach that combines supportive and dynamic elements, is suitable for 'difficult' patients, and may be cost-effective. Two illustrative causes are presented.

Adult↗
PubMed1988

Fresh terrain for medical record practitioners.

This article describes hospital bill audits and their purpose, what information is needed, when and where the audits are carried out, and the roles medical record practitioners can perform in this process.

Accounting↗
PubMed1987

Natural family planning.

It is now well accepted that a woman can conceive from an act of intercourse for a maximum of only about 7 days of her menstrual cycle. The reliability of natural family planning depends on identifying this window of fertility without ambiguity. Several symptomatic markers, cervical mucus and basal body temperature, have been used extensively and with considerable success in most women but failures occur. Ovarian and pituitary hormone production show characteristic patterns during the cycle. Urinary estrogen and pregnanediol measurements yield reliable information concerning the beginning, peak, and end of the fertile period, provided that the assays are accurate and performed on timed specimens of urine. We have developed such enzyme immunoassays for urinary estrogen and pregnanediol glucuronides that can be performed at home. In the early versions of the assays, enzyme reaction rates were measured by eye, but more recently, a simple photoelectronic rate meter has been used. The final problem to be solved is not technologic but whether women are sufficiently motivated to expend the same time and effort each day for 10 days a month, with less cost, on fertility awareness as they spend on making a cup of tea.

Adult↗
PubMed1986

Long-term follow-up in London Transplant Group recipients of cadaver renal allografts. The influence of HLA matching on transplant outcome.

The London Transplant Group followed 1341 patients with cadaver renal transplants, none of whom received cyclosporine, for six months to 14 years to determine the effect on graft survival of matching donor and recipient for HLA Class I antigens (HLA-A, -B, and -C) and Class II antigens (HLA-DR, -MT, and -DQ). Long-term graft survival was greatly improved by matching for HLA Class I antigens, especially HLA-B. Transplants that could not be matched for both B-locus antigens but were completely matched for Bw4/Bw6 also did very well. In addition, since 1978, excellent results have been obtained with HLA-DR and -DRw52/53 (HLA-MT) matching, but not with HLA-DQ matching. Multivariate analysis using the Cox regression model confirmed that combination Class I and Class II matching produced significant improvements in graft survival. Thus, transplants matched for HLA-DR plus HLA-B and those matched for HLA-MT plus HLA-B had excellent results--even better than those reported with cyclosporine treatment. Double HLA-MT incompatibilities yielded the poorest results. We conclude that this approach of combining the broad and narrow specificities of Class I and II is extremely practical and that appropriate matching of tissue types is clinically important.

Antibodies↗
PubMed1986

Teaching the psychotherapeutic method: some literary parallels.

There is a need for a theoretical account of the psychotherapeutic process or method, as distinct from psychotherapeutic or psychoanalytic theory itself. A four-stage model is presented which attempts to delineate the elements of the psychotherapeutic method: structure, space, discovery and description. This account puts discovery as the central theme in psychotherapy. The psychotherapeutic method as described is compared first with Medawar's account of the scientific method, and then with two literary versions of creativity. The conditions under which psychotherapeutic discovery occurs, scientific hypotheses arise and artistic activity takes place are structurally similar. The implications of this for teaching psychotherapy are discussed, especially in relation to the establishment and recognition of transferential experience.

Art↗
PubMed1986

Inability of rheumatologists to describe their true policies for assessing rheumatoid arthritis.

Eighty nine British and Australian rheumatologists took part in a study to discover how accurately they could describe their procedures for measuring disease severity in rheumatoid arthritis. The relative importance they attached to different clinical and laboratory variables showed a very wide variation, and these stated policies were generally poor at predicting their actual judgments when assessing 'paper patients' (r2 = 39%). Policies based on equal weighting of all variables, while also poor predictors (r2 = 41%), were nevertheless superior to their stated policies for 49 respondents. Policies calculated by judgment (linear regression) analysis were much more successful predictors (R2 = 73%). Unhurried, detailed interviews with four experienced rheumatologists provided carefully considered statements of assessment policy, but these also were poor predictors of routine assessments of outpatients (r2 = 34%) compared with policies calculated by clinical judgment analysis, even when these were applied to new data (R2 = 88%).

Arthritis, Rheumatoid↗