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Biomedical subjects

J West

Publications and source records attributed to J West.

At least 163 records · Page 9Linked to original sources

Tubulin is phosphorylated at tyrosine by pp60c-src in nerve growth cone membranes.

We show here that tubulin is the major in vivo substrate of the tyrosine-specific protein kinase pp60c-src in nerve growth cone membranes. Phosphotyrosine antibodies were used to demonstrate phosphotyrosyl residues in a subpopulation of alpha- and beta-tubulin that was highly enriched in a subcellular fraction of growth cone membranes from fetal rat brain. The presence of phosphotyrosine-modified isoforms of alpha- and beta-tubulin in vivo was confirmed by 32p labeling of rat cortical neurons in culture. Tubulin in growth cone membranes was phosphorylated at tyrosine in endogenous membrane phosphorylation reactions (0.068 mol phosphotyrosine/mol alpha-tubulin and 0.045 mol phosphotyrosine/mol beta-tubulin), and phosphorylation was specifically inhibited by antibodies directed against pp60c-src, which is localized in the growth cone membranes. pp60c-src was capable of directly phosphorylating tubulin as shown in immune complex kinase assays with purified brain tubulin. Phosphopeptide mapping revealed a limited number of sites of tyrosine phosphorylation in alpha- and beta-tubulin, with similar phosphopeptides observed in vivo and in vitro. These results reveal a novel posttranslational modification of tubulin that could regulate microtubule dynamics at the growth cone.

Animals↗

Topical timolol and serum lipoproteins.

Oral timolol taken for the treatment of systemic hypertension has been shown to affect adversely serum lipoprotein levels. In a 15-week study on 19 patients topical timolol therapy for raised intraocular pressure was found to have no significant adverse effect on serum lipoprotein levels. This is reassuring in view of the large number of patients on this form of long term therapy, and selection of the type of beta blocker to use should not be influenced by lipid changes associated with the oral form of the drug.

Administration, Topical↗

Loss of vision in one eye following scoliosis surgery.

A 50-year-old woman developed left sided total external ophthalmoplegia and complete visual loss, with evidence of choroidal non-perfusion, immediately following scoliosis surgery. The ocular movements recovered, but the eye remained blind. It is suggested that these lesions may have resulted from pressure on the orbital contents during surgery.

Blindness↗

A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' capsules) in the treatment of rheumatoid arthritis.

A multi-centre, double-blind, crossover study was carried out in 80 patients with rheumatoid arthritis to compare the efficacy and side-effect profiles of two formulations of indomethacin. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times a day for a period of 4 weeks before being crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by both investigator and patient indicated that controlled-release indomethacin tablets, 75 mg given at night, was as efficacous as immediate-release indomethacin capsules given 3-times daily. However, the controlled-release formulation had a superior side-effect profile with a reduced incidence of abdominal/epigastric pain compared to the immediate-release preparation.

Administration, Oral↗

A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' capsules) in the treatment of osteoarthritis.

The efficacy and side-effect profiles of two formulations of indomethacin were compared in a multi-centre, double-blind, crossover study in 77 patients with osteoarthritis. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times daily for a period of 4 weeks, after which patients were crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by the investigator and patient indicate that controlled-release indomethacin tablets, 75 mg given at night, were as efficacious as immediate-release indomethacin capsules, 25 mg given 3-times daily, in the treatment of osteoarthritis. The side-effect profiles of the two formulations were similar.

Administration, Oral↗

Differential activation of cytokine genes in normal CD4-bearing T cells is stimulus dependent.

Studies of cloned CD4+ T cell lines have shown that they can be separated into two distinct subsets with distinctions in their functional capabilities and by the differential release of either interleukin 2 (IL 2) (TH1/inflammatory type) or IL 4 (TH2/helper type) upon activation. To establish if in vivo-derived CD4+ T cells can exhibit distinct subsets we have investigated whether normal CD4+ T cells demonstrate differential expression of IL 2 and IL 4 mRNA, and secretion of IL 2 and IL 4 after primary stimulation in vitro. Utilizing the technique of in situ hybridization IL 2 and IL 4 gene expression in individual CD4+ T cells was readily detectable after concanavalin A (Con A) phytohemagglutinin (PHA) or pokeweed mitogen (PWM)-mediated activation. The frequencies of activated T cells producing IL 2 and IL 4 mRNA after Con A or PHA activation were approximately equivalent (30-40% of cells); however, after PWM activation the number of CD4+ T cells expressing IL 4 mRNA (78%) was more than twofold greater than the number of cells producing IL 2 mRNA (30%). Maximal levels of IL 2 gene expression occurred 24 h after mitogen activation whereas the highest levels of IL 4 mRNA were not detected until 48 h after mitogen activation. Similar distinctions in the kinetics of IL 2 and IL 4 secretion after mitogen activation were also found demonstrating good concordance in the observed expression of IL 2 and IL 4 mRNA and the levels of secreted lymphokines detected by bioassay. Most importantly, we have shown by in situ hybridization analysis that the majority of individual CD4+ T cells produce only IL 2 or IL 4 mRNA, and not both, after primary activation in vitro. By contrast, most CD4+ T cells activated in the presence of PMA and ionophore express both IL 2 and IL 4 mRNA. Our studies demonstrate that in normal, non-clonal populations of CD4+ T cells, the production of IL 2 and IL 4 is independently regulated in the majority of cells and appears to be stimulus dependent.

Animals↗

A monoclonal antibody to murine CD45R distinguishes CD4 T cell populations that produce different cytokines.

CD4 T cell clones have been shown to be functionally heterogeneous in the mouse. However, it is not known if normal CD4 T cells are also functionally heterogeneous, or whether functional specialization is a result of cloning and long-term culture. To approach this question, a monoclonal antibody reacting with a subset of CD4 T cells has been prepared by immunization of rats with different cloned T cell lines all sharing the same functional activity. This monoclonal antibody reacts with a subset of CD45 (T200) molecules by binding to a determinant requiring the expression of the second variable exon of the CD45 molecule. Some CD4 T cells bear high levels of this marker, while others react only weakly. This antibody was used to separate CD4 T cells into two subpopulations. The brightly staining population was found to produce interleukin (IL) 2 and not IL 4, while the weakly staining population produced IL 4 and not IL 2. These data demonstrate that CD4 T cells in normal mice are already functionally committed, and that they differentially express forms of CD45 that contain the second variable exon.

Animals↗

The eye of the hooded seal, Cystophora cristata, in air and water.

Multiple refractive state measurements were made on a male and female hooded seal (Cystophora cristata) when the eyes were exposed to air and to water. The measures, made by conventional retinoscopy and by photorefraction, show that the seals are moderately hyperopic (2-3 diopters) in water and moderately myopic (2-4 diopters) in air. No significant astigmatism was noted in either medium. The absence of refractive state variation over time suggests that an accommodative mechanism is insignificant or absent, although histological study indicates that the ciliary muscle is well developed. Photokeratoscopy, carried out on two animals with two keratoscopic instruments, show that the cornea is relatively flat (30 mm, or about one-half the diameter of the eye). Furthermore the cornea is only slightly astigmatic (less than 1 diopter). The refractive power of the external corneal surface (in air), calculated from a measurement of corneal refractive index of 1.378, amounts to only 10 or 11 diopters. As in the typical fish eye, hooded seal lenses are spherical or nearly spherical in shape (24-23 mm), and have short focal lengths (30-32 mm). Focal measures for rays at varying distances from the lens center indicate that spherical aberration is well corrected. There is no indication in this seal species, of a previously reported adaptation involving a highly astigmatic cornea which together with a slit pupil can minimize the optical effect of movement from water to air.

Air↗

Single-breath breath-holding estimate of pulmonary blood flow in man: comparison with direct Fick cardiac output.

1. Resting pulmonary blood flow (Q), using the uptake of the soluble inert gas Freon-22 and an indirect estimate of lung tissue volume, has been estimated during breath-holding (Qc) and compared with direct Fick cardiac output (Qf) in 16 patients with various cardiac disorders. 2. The effect of breath-hold time was investigated by comparing Qc estimated using 6 and 10 s of breath-holding in 17 patients. Repeatability was assessed by duplicate measurements of Qc in the patients and in six normal subjects. 3. Qc tended to overestimate Qf, the bias and error being 0.09 l/min and 0.59, respectively. The coefficient of repeatability for Qc in the patients was 0.75 l/min and in the normal subjects was 0.66 l/min. For Qf it was 0.72 l/min. There was no significant difference in Qc measured at the two breath-hold times. 4. The technique is simple to perform, and provides a rapid estimate of Q, monitoring acute and chronic changes in cardiac output in normal subjects and patients with cardiac disease.

Adult↗

Nurse-initiated health promotion prompting system in an internal medicine residents' clinic.

Although cure of many diseases depends on early detection, screening schemes have been difficult to implement in busy clinic environments. We describe the testing of a nurse-initiated prompting system for six health promotion and disease prevention procedures in an internal medicine residents' clinic at a university-affiliated community program. Maneuvers investigated were breast examination, pelvic examination and Pap smear, rectal examination in men, mammogram, stool guaiac test, and blood glucose determination. A nurse reviewed the charts and used a list in the front of each chart to prompt residents in the experimental group. Residents in the control group were not prompted. A significant improvement (P less than .05) in performance was seen in the prompted group. Performance of rectal examination and mammograms improved most, increasing from 41% to 93% and 18% to 64%, respectively. There were no significant changes in the control group. This simple nurse-initiated prompting system improved the performance of health promotion and disease prevention maneuvers.

Adult↗

Public opinion, public policy, and HIV infection.

An analysis of the interplay between public opinion and public policy in terms of HIV infection yielded a four-stage framework for considering the development of public policy in relation to a highly charged issue. The phases are denial, irrationality, acceptance, and the development of a rational response. As we move into Phase 4 in relation to HIV infection, we should take a lesson from the history of the development of public policy for persons with disabilities and promote strong federal leadership and a federal antidiscrimination policy that includes persons with HIV infection as a part of the group of persons with disabilities.

HIV Infections↗

Doing well with AIDS: three case illustrations.

This report focuses on the abilities of three people diagnosed with acquired immune deficiency syndrome (AIDS) to maximize their state of well-being. The purpose of this ongoing investigation is to identify factors that may help enhance AIDS patients' states of well-being, ultimately achieving the provision of holistic and life-giving nursing care. A naturalistic approach was used to generate an understanding of the concept, "doing well." Five themes regarding "doing well" with AIDS emerged from the interview data. These themes include: autonomy/mastery over the disease; existential/spiritual journey toward understanding; self-acceptance; staying active and involved; and positive thinking. Nursing implications of these themes are discussed.

Acquired Immunodeficiency Syndrome↗

Automated sequence reading and analysis.

We report on a system developed by Bio-Rad Laboratories, Inc. which combines automated reading of DNA sequencing autoradiograms with comprehensive software for shotgun overlapping of the readings, analysis of the sequences derived and searching of databases. Reading is accomplished using a high speed optical scanner and pattern recognition software operating on a personal computer. Overlapping, analysis and database searching software each incorporate significant advances over prior systems.

Algorithms↗

Direct Fick cardiac output: are assumed values of oxygen consumption acceptable?

The use of assumed values of oxygen consumption has become an accepted practice in the calculation of direct Fick cardiac output. A survey showed that the assumed values in common use were derived from basal metabolic rate studies on normal subjects, a use which may not be valid. We have compared previous assumed values based on basal metabolic rate or cardiac catheterization studies with those obtained by direct measurement in 80 patients (age range 38-78 years) with various cardiac disorders. Comparison of the assumed and directly measured values of indexed oxygen consumption and the cardiac index showed large discrepancies, with over half the values differing by more than +/- 10% and many by more than +/- 25% from the measured value. Assumed values of oxygen consumption should be used with caution when calculating cardiac output during cardiac catheterization procedures, because large errors can result. The equations of LaFarge and Miettinen gave the closest approximation to the measured data and their use is recommended in preference to values predicted from basal metabolic rate studies.

Adult↗