[When one does not have the blues, then one has some spirit].
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Biomedical subjects
Publications and source records attributed to R Henry.
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The light-harvesting chlorophyll a/b protein (LHCP) is an integral thylakoid membrane protein. It is made in the cytosol as a precursor (pLHCP), imported into chloroplasts, and subsequently integrated into thylakoids. Integration of pLHCP into thylakoids requires a stromal protein factor that functions in part to maintain the solubility and integration competence of pLHCP. Recently, it was reported that unfolded pLHCP was sufficient for integration and that the stromal factor, identified as the plastid Hsp70, was required only to prevent pLHCP refolding [Yalovsky, S., Paulsen, H., Michaeli, D., Chitnis, P. R. & Nechushtai, R. (1992) Proc. Natl. Acad. Sci. USA 89, 5616-5619]. Our studies, using more rigorous criteria for integration, show that unfolded pLHCP is not sufficient; stromal factor is an absolute requirement for integration. Furthermore, experiments with purified Hsp70 as well as Hsp70-depleted stromal extract demonstrate that Hsp70 is not the stromal factor. These results plus the finding that pLHCP diluted out of urea is relatively stable as a substrate for integration point to an additional role for the stromal factor in targeting and/or membrane translocation.
OBJECTIVE: To determine whether the availability of beta 2 agonist inhalers without prescription leads to undertreatment of asthma. DESIGN: Cross sectional study of adequacy of treatment in asthmatic subjects who purchased beta 2 agonist inhalers and subjects who obtained inhalers by prescription. SETTING: Community pharmacies in New South Wales, Australia. SUBJECTS: 403 eligible consecutive asthmatic subjects aged 13 to 55 purchasing salbutamol metered dose inhalers over the counter or by prescription; 197 attended for follow up and spirometry and 139 returned 14 day symptom, peak flow, and medication diaries. MAIN OUTCOME MEASURES: Severity of asthma assessed on frequency of day time and night time wheezing, frequency of inhaler use, and peak expiratory flow rates. Adequacy of treatment according to published guidelines. RESULTS: Of the 139 patients who completed the diary 83, (60%) purchased their inhalers without prescription and 83 were undertreated. The characteristics of patients in the prescription and purchasing groups were similar. Multiple logistic regression analysis identified use of non-prescribed salbutamol as being associated with a 2.9-fold increase in the odds of undertreatment (95% confidence interval 1.3 to 6.8). Smoking increased the odds of undertreatment (3.3, 1.2 to 9.5) and use of a peak flow meter reduced the odds (0.11, 0.04 to 0.34). Adjustment for frequency of consultation made use of non-prescription salbutamol insignificant (1.4, 0.55 to 3.8). Attitudes to services provided by doctors and pharmacists were favourable and not associated with undertreatment. CONCLUSION: Over the counter purchase of salbutamol is associated with infrequent consultation with doctors and undertreatment of asthma.
Many thylakoid proteins are cytosolically synthesized and have to cross the two chloroplast envelope membranes as well as the thylakoid membrane en route to their functional locations. In order to investigate the localization pathways of these proteins, we over-expressed precursor proteins in Escherichia coli and used them in competition studies. Competition was conducted for import into the chloroplast and for transport into or across isolated thylakoids. We also developed a novel in organello method whereby competition for thylakoid transport occurred within intact chloroplasts. Import of all precursors into chloroplasts was similarly inhibited by saturating concentrations of the precursor to the OE23 protein. In contrast, competition for thylakoid transport revealed three distinct precursor specificity groups. Lumen-resident proteins OE23 and OE17 constitute one group, lumenal proteins plastocyanin and OE33 a second, and the membrane protein LHCP a third. The specificity determined by competition correlates with previously determined protein-specific energy requirements for thylakoid transport. Taken together, these results suggest that thylakoid precursor proteins are imported into chloroplasts on a common import apparatus, whereupon they enter one of several precursor-specific thylakoid transport pathways.
The management of acute bronchiolitis is mainly supportive, but infants require minimal handling. Of those who are hospitalized, less than 3% require intensive care and ventilation but in these children the condition is life threatening. Oxygen, fluid replacement and careful observation remain the cornerstones of management. Bronchodilators should be avoided in young infants and antiviral therapy should only be considered in critically ill infants who have an underlying cardiopulmonary condition.
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The purpose of this paper is to demonstrate the use of some statistical methods for examining trends in ambient ozone air quality downwind of major urban areas. To this end, daily maximum 1-hr ozone concentrations measured over New Jersey, metropolitan New York City and Connecticut for the period 1980 to 1989 were assembled and analyzed. This paper discusses the application of the bootstrap method, extreme value statistics and a nonparametric test for evaluating trends in urban ozone air quality. The results indicate that although there is an improvement in ozone air quality downwind of New York City, there has been little change in ozone levels upwind of New York City during this ten-year period.
Increasing the number of faculty with expertise in addiction medicine is one of the challenges facing the medical community in the 1990s. To meet this challenge, the Society of Teachers of Family Medicine created a faculty development course to increase the expertise of family practice faculty involved in teaching residents. The authors describe the development, implementation, and consequences of the five-day intensive course that was taught to 165 participants at ten sites in 1990. The participants' self-reporting before and three months after the course showed significant increases in the numbers of participants who taught addiction medicine in eight of 11 clinical situations. The authors conclude that the course represents a model of faculty development in addiction medicine that is applicable to other specialties and health professions.
The management of croup relies upon the traditional clinical skills of observation and examination. Parental involvement is essential and the appropriate reassurance of the patient is important. Endotracheal intubation is required only in a small percentage of children whose airway is compromised to such a degree as to produce fatigue and/or near occlusion.
European patients with human immunodeficiency virus type 1 (HIV-1) infection have been reported to have lower titers of anti-p24 antibody than Central African HIV seropositive patients. Recently, black HIV positive patients in the United States were reported to be more likely to have detectable anti-p24 antibodies, less p24 antigenemia, and higher combined serum immunoglobulins than white HIV positive patients. We measured individual total serum immunoglobulins in 853 HIV positive patients (94% male; 58% white and 42% black) on their initial medical evaluation and compared them with CD4+ T-cell counts. Blacks had notably higher IgG levels (p = 0.001) across the entire spectrum of CD4+ T-cell counts. Serum IgM levels were slightly higher in blacks. IgA levels were not significantly different between the races, although the trend (p = 0.006) was toward higher levels in whites. We also measured these three serum immunoglobulins in 60 HIV seronegative, healthy blood donors (30 black and 30 white). In this control group, blacks had statistically higher IgG and IgA levels than whites. A review of the literature prior to the HIV/acquired immune deficiency syndrome epidemic also supports the view that racial differences in IgG levels are not specific for HIV infection. We speculate that racial differences in humoral immunity, independent of geography or strain of HIV, may account for differences in anti-HIV antibody levels and HIV antigenemia.
The analysis of hydrogenated cyclic fatty acid monomers isolated from heated linseed and sunflower oils is achieved by gas chromatography-tandem mass spectrometry of their pentafluorobenzyl esters. Collisionally activated dissociation of the carboxylate anions produced by electron-capture ionization shows remote charge-site fragmentation that allows location of cyclopentane and cyclohexane rings by examining the resulting mass-analysed ion kinetic energy spectra. Oxidative ozonolysis of the methyl esters of the unsaturated cyclic fatty acid monomers allows location of some double bonds. However, preliminary results obtained with remote charge fragmentation of synthetic unsaturated models make this approach an alternative for double bond location in the cyclic fatty acid monomers isolated from heated fats.
Addressed both the psychological frailness and strength in an AIDS-affected community. The gay community in Sydney, Australia, was represented by men who were seropositive (n = 60) and voluntary caregivers (n = 60). They were compared with two samples of men outside the gay community, who were ill with non-AIDS-related medical conditions (n = 30), and well (n = 30). Their psychological frailness and strength were measured by content analysis scales. Both the seropositive men and the caregivers showed the frailness of anxiety, indirectly expressed anger and helplessness, but also the compensating strength of greater personal competence and good feeling relative to the other men. The men who were seropositive or had other illnesses showed the predicted frailness of anxiety and depression but neither indirectly expressed anger nor helplessness. The seropositive men and caregivers of the gay community differed from each other only in the high levels of depression of the former.
The high-performance liquid chromatographic separation and quantitation of conjugated bile salts from pig bile is reported. Synthetic standards and bile samples were chromatographed on a C18 reversed phase column using acetonitrile/water/tetrabutyl ammonium phosphate as an isocratic mobile phase at a flow rate of 1 mL/min. Detection of the ion-pairs was at 214 nm. The method permits efficient separation of all conjugated pig biliary bile salts without prior modification or treatment of the samples. Analysis of 12 pig biles showed that 85% of the bile salts are conjugated to glycine. The three main conjugated bile salts were glyco-3 alpha,6 alpha,7 alpha-trihydroxy-5 beta-cholanoic acid (GHC), glyco-3 alpha,7 alpha-dihydroxy-5 beta-cholanoic acid (GCDC), and glyco-3 alpha,6 alpha-dihydroxy-5 beta-cholanoic acid (GHDC). Glyco-3 alpha-hydroxy-6-oxo-5 beta-cholanoic acid (G3 alpha 6oxo), tauro-3 alpha,7 alpha-dihydroxy-5 beta-cholanoic acid (TCDC), tauro-3 alpha,6 alpha,7 alpha-trihydroxy-5 beta-cholanoic acid (THC), and tauro-3 alpha,6 alpha-dihydroxy-5 beta-cholanoic acid (THDC) were found to contribute each for 4 to 5% to the total. An excellent correlation was found between the sum of conjugated bile salts quantitated by high-performance liquid chromatography (HPLC) and values obtained by conventional enzymatic assay. Simplicity, efficiency and relative rapidity of the method render it suitable for routine analyses.
Covalent linkage of the A chain of ricin to the LICR-LOND-Fib75 monoclonal antibody produced an immunotoxin, Fib75-SS-ricin A, which demonstrated immunospecific toxicity to human bladder carcinoma cells in tissue culture (Forrester et al., 1984). The present studies have shown that ricin B chain potentiates the toxicity of the immunotoxin by two orders of magnitude and also significantly increases the rate of protein synthesis inhibition. Using immunoelectron microscopy, the receptor-mediated endocytosis and intracellular routing of the immunotoxin was studied with and without ricin B chain treatment after immunolocalisation of the conjugate. Fib75-SS-ricin A was internalised by the EJ cells predominantly in uncoated pits and vesicles and directed to the endosomes. Some degradation of the complex appeared to take place in multivesicular endosomes at early timepoints and 24 h after internalisation, most of the immunotoxin was found in lysosomes. Some ricin A chain epitopes were detected in Golgi vesicles. Cells treated with immunotoxin and ricin B chain endocytosed the complex predominantly in coated pits and coated vesicles. Using pre-embedding immunoperoxidase techniques, ricin chains were found in the whole Golgi complex and most of the conjugate escaped lysosomal degradation. Internalised immunotoxin was recycled back to the plasma membrane in an active form associated with vesicles which appeared to be derived predominantly from multivesicular endosomes. A similar mode of recycling has recently been reported (McIntosh et al., 1990) for ricin holotoxin in the same cell line. These observations may explain the potentiating effect of toxin B chains in the antibody-directed targeting of toxin A chains.
In June 1990 a meeting of Paediatric Respiratory Physicians was held near Adelaide. The guidelines for assessing and treating asthma as prepared by the Thoracic Society of Australia and New Zealand for the management of patients with asthma was considered. Although not explicitly stated, these guidelines were designed for adult asthmatics. There was complete agreement that a companion statement was needed to take into account differences between the management of children and adults. This document fulfils that role. Further recommendations are found in a statement prepared by Australian and New Zealand respiratory paediatricians following a workshop in June 1989. This present statement should be read in association with the previous documents.
These are case reports of two children with structurally normal hearts and with normal coronary arteries, who survived myocardial infarction in the early neonatal period. They are only the third and fourth reported survivors of neonatal myocardial infarction and the first in which hypercholesterolemia is postulated to have played an important role. The most likely cause of the myocardial infarction was thrombosis or thromboembolism. Changes in hemostatic function associated with hypercholesterolemia may be relevant.