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Biomedical subjects

J Holmes

Publications and source records attributed to J Holmes.

At least 91 records · Page 5Linked to original sources

Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice.

Antigens and infectious agents that stimulate interferon alpha(IFN-alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN-alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells.

Animals↗

Extended longitudinal study of uterine activity among low-risk women.

Eighty-nine black women without major medical risks for preterm labor participated in this longitudinal, prospective study for the evaluation of usual prelabor uterine activity and for the assessment of how gestational age, time of day, maternal weight, age, and parity affected contraction frequency. Participants wore an ambulatory tocodynamometer for 72 consecutive hours at three points in gestation during the second and early third trimesters while engaged in usual home and work activity. Data obtained from the 81 women with uncomplicated term pregnancies demonstrated a significant increase in contraction frequency with advancing gestational age between 22 and 33 weeks. After 26 weeks, significantly more uterine activity occurred at night. Perhaps because of detection difficulties, contraction frequency was inversely related to maternal weight in women weighing greater than 112% ideal weight. Maternal age and parity did not affect contraction frequency. Contraction characteristics of eight women experiencing preterm labor or medically indicated preterm delivery are described.

Adolescent↗

Use of the Home Ovarian Monitor in pregnancy avoidance.

The application of the Home Ovarian Hormone Monitor to the avoidance of pregnancy by periodic abstinence has been explored. No woman had difficulty with the daily urine testing, and their results consistently identified the distinctive hormone pattern of the ovulatory cycle and the day of ovulation and correlated closely with the mucus symptoms. The tests gave 4 days or more warning of ovulation in 99% of cycles and allowed intercourse to be resumed 1 to 3 days after ovulation in 88%, giving a mean period of abstinence of 7 days. No pregnancy occurred from intercourse during the late safe days defined by the Monitor, but some early-day pregnancies occurred through long sperm survivals of 6 to 8 days, mostly during the return of fertility after breastfeeding. Rules for the avoidance of pregnancy, with the minimum of testing on the basis of these results, are given.

Adult↗

Factors influencing choice of specialty and location of residency.

Students recently graduating from the University of Oklahoma College of Medicine are leaving the state for their postgraduate training and entering nonprimary care fields in increasing numbers. This study identifies the major determinants for training location as having to do with the anticipated quality of the program, and for specialty as having to do with positive experiences on clerkship and the perceived characteristics of the field, including potential controllability of practice. Other factors of significance include lifestyle, standard of living and opinions of others. A striking finding was the negative view of Oklahoma held by our graduates.

Adult↗

Glutathione-s-transferase pi expression in leukaemia: a comparative analysis with mdr-1 data.

Drug resistance in haemopoietic cells may be partly related to the expression of the glutathione-s-transferase (GST) pi and mdr-1 genes. We have used RNA slot blotting techniques to investigate the expression of GST pi in peripheral blood and bone marrow of eleven normal subjects, nine patients with myelodysplastic syndrome (MDS), eighteen patients with acute myeloblastic leukaemia (AML), and thirty-two patients with chronic lymphocyte leukaemia (CLL). We found increased expression of GST pi in 8 of 9 MDS, (7 peripheral blood, 1 bone marrow) 12 of 18 AML (5 peripheral blood, 7 bone marrow; 4 of 5 untreated, 1 of 5 secondary, 7 of 11 relapse or refractory) and in the peripheral blood of 24 of 32 CLL (3 of 7 untreated, 21 of 25 treated) relative to normal controls. Increased expression of GST pi can occur at any stage of disease and shows no clear relation to mdr-1 expression except, possibly, in CLL. In 3 AML patients GST pi transcript levels were the same or lower on relapse compared to presentation. Upregulation of the GST pi gene could not be demonstrated in 2 CLL patients in response to treatment with intermittent chlorambucil.

Adult↗

Strand-specific mismatch correction in nuclear extracts of human and Drosophila melanogaster cell lines.

Nuclear extracts derived from HeLa and Drosophila melanogaster KC cell lines have been found to correct single base-base mispairs within open circular DNA heteroduplexes containing a strand-specific, site-specific incision located 808 base pairs from the mismatch. Correction in both extract systems is strand specific, being highly biased to the incised DNA strand. Different mispairs within a homologous set of heteroduplexes were processed with different efficiencies (G.T greater than G.G approximately equal to A.C greater than C.C), and correction was accompanied by mismatch-dependent DNA synthesis localized to the region spanning the mispair and the strand break, thus demonstrating that mismatch recognition is associated with the repair reaction. Correction of each of these heteroduplexes was abolished by aphidicolin but was relatively insensitive to the presence of high concentrations of ddTTP, indicating probable involvement of alpha and/or delta class DNA polymerase(s). These findings suggest that higher eukaryotic cells possess a general, strand-specific mismatch repair system analogous to the Escherichia coli mutHLS and the Streptococcus pneumoniae hexAB pathways, systems that contribute in a major way to the genetic stability of these bacterial species.

Animals↗

Traumatic hyphaema in a haemophiliac.

A case is presented of a 9-year-old haemophiliac boy who sustained a traumatic hyphaema with secondary haemorrhage. Conservative management was successful in preventing complications, and normal vision was retained.

Child↗

A family study of congenital X linked sideroblastic anaemia.

We report on the cytogenetic findings in a family study of pyridoxine responsive, X linked sideroblastic anaemia. An increase in the number of X chromosomes was observed in a small proportion of metaphases prepared from five female members, but these findings did not strictly correlate with the carrier status of the condition. No consistent cytogenetic abnormality could be identified or associated with this rare familial condition. The diagnosis and counselling of carriers of this condition is discussed.

Adolescent↗

Lymphokine control of in vivo immunoglobulin isotype selection.

Several specific conclusions can be drawn from these studies: 1. IL-4 is required for the generation of both primary polyclonal and secondary antigen-specific IgE responses in vivo. 2. IL-4 is required to maintain established, ongoing, antigen-specific and polyclonal IgE responses. 3. Most, but not all, polyclonal IgE production during a secondary immune response is IL-4-dependent. Memory B cells that have already switched to IgE at the DNA level may no longer require stimulation with IL-4 to be induced to secrete IgE. 4. The generation of a secondary IgE response is not dependent upon the presence of IL-4 during primary immunization. However, if IL-4 is not present during primary immunization, it is required during secondary immunization for the generation of an IgE response. 5. IL-4 does not appear to be required for the generation of in vivo IgG1 responses, and in at least some instances, does not contribute significantly to the generation of IgG1 responses in vivo. 6. A late-acting form of T-cell help other than IL-4 appears to be required for the generation of an IgE, but not an IgG1 response. 7. An antibody that inhibits IL-4 binding to IL-4 receptors affects Ig isotype selection in the same way as an antibody that neutralizes IL-4. 8. IFN-gamma can act in both spontaneous and induced immune responses to suppress IgE production. 9. IFN-gamma can also suppress IgG1 production and stimulate IgG2a production. However, IFN-gamma appears to suppress polyclonal IgG1 responses more than antigen-specific IgG1 responses, and it enhances, but is not required for, the generation of IgG2a responses. 10. IFN-alpha appears to resemble IFN-gamma in its ability to inhibit IgE and enhance IgG2a responses in GaM delta-injected mice, but it requires the presence of IFN-gamma to suppress IgG1 production in these mice. 11. Both IFN-alpha and IFN-gamma appear to be able to decrease IgE production in some human patients. 12. There is no direct evidence that IL-5 contributes to the generation of in vivo antibody responses. Two general conclusions may also be drawn.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Driving safety after brain damage: follow-up of twenty-two patients with matched controls.

Driving after brain damage is a vital issue, considering the large number of patients who suffer from cerebrovascular and traumatic encephalopathy. The ability to operate a motor vehicle is an integral part of independence for most adults and so should be preserved whenever possible. The physician may estimate a patient's ability to drive safely based on his own examination, the evaluation of a neuropsychologist, and a comprehensive driving evaluation--testing, driving simulation, behind-the-wheel observation--with a driving specialist. This study sought to evaluate the ability of brain-damaged individuals to operate a motor vehicle safely at follow-up. These patients had been evaluated (by a physician, a neuropsychologist, and a driving specialist) and were judged able to operate a motor vehicle safely after their cognitive insult. Twenty-two brain-damaged patients who were evaluated at our institution were successfully followed up to five years (mean interval of 2.67 years). Patients were interviewed by telephone. Their driving safely was compared with a control group consisting of a close friend or spouse of each patient. Statistical analysis revealed no difference between patient and control groups in the type of driving, the incidence of speeding tickets, near accidents, and accidents, and the cost of vehicle damage when accidents occurred. The patient group was further divided into those who had, and those who had not experienced driving difficulties so that initial neuropsychologic testing could be compared. No significant differences were noted in any aspect of the neuropsychologic test battery. We conclude that selected brain-damaged patients who have passed a comprehensive driving assessment as outlined were as fit to drive as were their normal matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic↗

T help requirements for the generation of an in vivo IgE response: a late acting form of T cell help other than IL-4 is required for IgE but not for IgG1 production.

To further define requirements for T cell help in the stimulation of an in vivo IgE response, we studied a system in which the injection of mice with a goat antibody to mouse IgD (GaMD) stimulates large polyclonal IgG1 and IgE responses. In this system, both responses are blocked by anti-CD4 antibody, but only the IgE response is blocked by (anti-IL-4) antibody. Anti-CD4 antibody, if injected 5 days after GaMD, was found to inhibit the GaMD-induced IgE response to a much greater extent than the IgG1 response, even though both responses occur simultaneously and are inhibited to an equal extent by optimal or suboptimal doses of anti-CD4 antibody administered 2 days after GaMD. Even a suboptimal, 50-micrograms dose of anti-CD4 antibody, when injected 5 days after GaMD, inhibited the IgE response to a much greater extent than did an optimal 10-mg dose of anti-IL-4 antibody injected at the same time, even though 10 mg of anti-IL-4 antibody more completely inhibited GaMD-induced IgE production than did 50 micrograms of anti-CD4 antibody when injected 2 days after GaMD. These observations provide evidence that a late acting form of T cell help other than IL-4 is important for the generation of an IgE response but not an IgG1 response in GaMD-immunized mice.

Animals↗

Changes in seasonal mortalities with improvement in home heating in England and Wales from 1964 to 1984.

Changes in summer (July-September) and winter (January-March) mortalities of people aged 70-74 in England and Wales from 1964 to 1984 were compared with possible causal factors. Summer mortalities were little affected by annual temperature or influenza epidemics and fell from 1972-1975 for all causes, coronary and respiratory causes, while cerebrovascular mortality fell more rapidly from that time. Cigarette consumption also fell from 1972-1975; falling consumptions of total fat from 1970 and saturated fat from 1972-1975 probably also contributed to the fall in arterial deaths, and likewise falls in prescription rates for tranquillisers and sedatives from 1976-1978 to the fall in respiratory deaths. From 1964 to 1984 use of central heating increased from 13% to 69% of households, domestic fuel consumption increased, and excess mortality in winter from respiratory disease declined by 69%, even relative to summer mortality and when adjusted for varying coldness of winters. The improvement was partly explained by a decline in influenza epidemics. By contrast, excess mortalities in winter from coronary and cerebrovascular disease, although rising in some early influenza epidemics, did not fall significantly as home heating improved. These thrombotic deaths together accounted for 56% of the total excess winter mortality by 1984. The findings support other indications that most of the excess mortality from arterial thrombosis in winter in England and Wales is due to brief excursions outdoors rather than to low indoor temperatures.

Aged↗