Bio

Publications


2013

Gathara, D;, Irimu G;, Kihara H;, Maina C;, Mbori-Ngacha DA;, Mwangi J;, Allen E;, English M.  2013.  Hospital outcomes for paediatric pneumonia and diarrhoea patients admitted in a tertiary hospital on weekdays versus weekends: a retrospective study. Abstract

Background: Quality of patient care in hospitals has been shown to be inconsistent during weekends and night- time hours, and is often associated with reduced patient monitoring, poor antibiotic prescription practices and poor patient outcomes. Poorer care and outcomes are commonly attributed to decreased levels of staffing, supervision and expertise and poorer access to diagnostics. However, there are few studies examining this issue in low resource settings where mortality from common childhood illnesses is high and health care systems are weak. Methods: This study uses data from a retrospective cross-sectional study aimed at “ evaluating the uptake of best practice clinical guidelines in a tertiary hospital ” with a pre and post intervention approach that spanned the period 2005 to 2009. We evaluated a primary hypothesis that mortality for children with pneumonia and/or dehydration aged 2 – 59 months admitted on weekends differed from those admitted on weekdays. A secondary hypothesis that poor quality of care could be a mechanism for higher mortality was also explored. Logistic regression was used to examine the association between mortality and the independent predictors of mortality. Results: Our analysis indicates that there is no difference in mortality on weekends compared to weekdays even after adjusting for the significant predictors of mortality (OR = 1.15; 95% CI 0.90 -1.45; p = 0.27). There were similarly no significant differences between weekends and weekdays for the quality of care indicators, however, there was an overall improvement in mortality and quality of care through the period of study. Conclusion: Mortality and the quality of care does not differ by the day of admission in a Kenyan tertiary hospital, however mortality remains high suggesting that continued efforts to improve care are warranted

2012

Irimu, GW, Gathara D, Zurovac D, Kihara H, Maina C, Mwangi J, Mbori-Ngacha D, Todd J, Greene A, English M.  2012.  Performance of health workers in the management of seriously sick children at a Kenyan tertiary hospital: before and after a training intervention., 2012. PloS one. 7(7):e39964. Abstract

Implementation of WHO case management guidelines for serious common childhood illnesses remains a challenge in hospitals in low-income countries. The impact of locally adapted clinical practice guidelines (CPGs) on the quality-of-care of patients in tertiary hospitals has rarely been evaluated.

2011

Irimu, GW.  2011.  Uptake of best-practice recommendations for management of acutely ill children admitted in Kenyatta National Hospital: a longitudinal study employing participatory action research in a complex environment. Abstract

The need for improving practice in low-income settings has been demonstrated in recent research assessing the quality of hospital care. Consequently, the Ministry of Health developed clinical practice guidelines and an evidenced-based programme for their dissemination. This thesis explored what factors influence the uptake of the best-practice recommendations in a university teaching hospital. This thesis used a mixed methods research approach that utilized a before and after design and participatory action research. This approach recognizes that health recommendations are compiled for universal use, but that their successful implementation requires particular attention to the individual and complex socio-political contexts of each setting, both at the micro and -macro level, which in this case was the Kenyatta National Hospital (KNH). This thesis is supported by eighteen months of participant observation, based on ethnographic research methodology and action research. Patients' care was largely inconsistent with best-practice recommendations, with nine of the 17 key indicators having performance of below 10% in the pre-intervention period. The intervention had an absolute effect size of over 20% in eight of the 17 key indicators; three of which had an effect size of over 50%. The indicators that required collective efficacy achieved performance of less than 10% in the post-intervention period. The activities during the action research component failed to predict the trend in practitioners' performance, illustrating the difficulty of gaining a holistic understanding of the quantitative results using component parts of the qualitative results as the lens. The notion of professionalism provided an overarching understanding of the implementation process. There were clear gaps between the stated values espoused in the ideal of professionalism and the observed actions of professionals in KNH. Gaps spanned knowledge management, expertise and skills, teamwork, conscientiousness and patient centeredness. I attributed the gaps in professionalism to complexity of professional development.

English, M, Wamae A, Nyamai R, Bevins B, Grace Irimu, R W Nduati.  2011.  Implementing locally appropriate guidelines and training to improve care of serious illness in Kenyan hospitals: a story of scaling-up (and down and left and right)., 2011 Mar. Archives of disease in childhood. 96(3):285-90.
Opondo, C, Ayieko P, Ntoburi S, Wagai J, Opiyo N, Grace Irimu, R W Nduati, Allen E, Carpenter J, English M.  2011.  Effect of a multi-faceted quality improvement intervention on inappropriate antibiotic use in children with non-bloody diarrhoea admitted to district hospitals in Kenya., 2011. BMC pediatrics. 11:109. Abstract

There are few reports of interventions to reduce the common but irrational use of antibiotics for acute non-bloody diarrhoea amongst hospitalised children in low-income settings. We undertook a secondary analysis of data from an intervention comprising training of health workers, facilitation, supervision and face-to-face feedback, to assess whether it reduced inappropriate use of antibiotics in children with non-bloody diarrhoea and no co-morbidities requiring antibiotics, compared to a partial intervention comprising didactic training and written feedback only. This outcome was not a pre-specified end-point of the main trial.

English, M, Nzinga J, Mbindyo P, Ayieko P, Grace Irimu, R W Nduati, Mbaabu L.  2011.  Explaining the effects of a multifaceted intervention to improve inpatient care in rural Kenyan hospitals--interpretation based on retrospective examination of data from participant observation, quantitative and qualitative studies., 2011. Implementation science : IS. 6:124. Abstract

We have reported the results of a cluster randomized trial of rural Kenyan hospitals evaluating the effects of an intervention to introduce care based on best-practice guidelines. In parallel work we described the context of the study, explored the process and perceptions of the intervention, and undertook a discrete study on health worker motivation because this was felt likely to be an important contributor to poor performance in Kenyan public sector hospitals. Here, we use data from these multiple studies and insights gained from being participants in and observers of the intervention process to provide our explanation of how intervention effects were achieved as part of an effort to better understand implementation in low-income hospital settings.

2010

Senga, J, Ndiritu M, Osundwa J, Grace Irimu, R W Nduati, English M.  2010.  Computer aided learning to link evidence to paediatric learning and practice: a pilot in a medical school in a low income setting. AbstractWebsite

Bridging the gap between research evidence and practice is problematic in low income settings. Wereport medical students' experience with a pilot computer aided learning (CAL) program developed to enable students to explore research evidence supporting national guidelines. We asked 50 students to enter data from pre-set clinical scenarios, diagnose the severity of pneumonia/asthma and suggest treatment and then compare their diagnosis and treatment with that suggested by a computer algorithm based on the guidelines. Links to evidence supporting the guideline-suggested diagnosis and treatment were provided. Brief evidence summaries and video clips were accessed by 92% of students and full text articles by 86%. The majority of the students showed an interest in the CAL approach and suggested the scope of the approach be expanded to other illnesses. Such a system might provide one means to help students understand the link between research and policy and ultimately influence practice.

2009

Nzioki, C, Grace Irimu, R W Nduati, Musoke R, English M.  2009.  AUDIT OF CARE FOR CHILDREN AGED 6 TO 59 MONTHS ADMITTED WITH SEVERE MALNUTRITION AT KENYATTA NATIONAL HOSPITAL, KENYA., 2009 Sep. International health. 1(1):91-96. Abstract

We conducted a prospective audit of 101 children with severe malnutrition aged 6 to 59 months admitted to Kenyatta National Hospital, Kenya's largest tertiary level health facility, from February-April 2008. A structured tool was prepared to capture data to allow assessment of implementation of the WHO guidelines steps 1-8. Overall, 58% of children had marasmus and 47% of children were younger than one year old. Common co-morbidities at admission were diarrhoea (70.3%) and pneumonia (51.4%). The highest degree of implementation was observed for Step 5, treatment of potentially severe infections (90%, (95% CI 85.1-96.9)). Only 55% of the patients had F75 prescribed although this starter formula was available in this hospital. There was a delay in initiating feeds with a median time of 14.7 hours from the time of admission. There was modest implementation of Step 2, ensuring warmth (46.5%, 36.8-56.2), Step 3, treat dehydration (54.9%, 43.3-66.5) and Step 4, correct electrolyte imbalance, (45.5%, 35.6-55.8%). There was least implementation of Step 8, transition to catch-up feeding (23.8%, 13.6-34.0). We conclude that quality of care for children admitted with severe malnutrition at KNH is inadequate and often does not follow the WHO guidelines. Improving care will require a holistic and not simply medical approach.

1988

Calva, E, Puente JL, Calva JJ.  1988.  Research opportunities in typhoid fever: epidemiology and molecular biology., 1988 Nov. BioEssays : news and reviews in molecular, cellular and developmental biology. 9(5):173-7.
Kumar, S, Mehta D, Singh S, Garg ML, Mangal PC, Trehan PN.  1988.  Biokinetics of lead in various mouse organs/tissues using radiotracer technique., 1988 Nov. Indian journal of experimental biology. 26(11):860-5.
Hubbard, WC, Alley MC, McLemore TL, Boyd MR.  1988.  Profiles of prostaglandin biosynthesis in sixteen established cell lines derived from human lung, colon, prostate, and ovarian tumors., 1988 Sep 1. Cancer research. 48(17):4770-5. Abstract

The profiles of prostanoid biosynthesis from endogenous arachidonic acid in 16 established cell lines derived from 4 histological classes of human carcinomas were determined by capillary gas chromatography-mass spectrometry. Detectable quantities of prostanoids were isolated from the culture medium of cell lines representative of the different histological classes of human tumors: colorectal adenocarcinomas (one of three cell lines); ovarian adenocarcinomas (one of three cell lines); prostate adenocarcinomas (zero of two cell lines); non-small cell carcinomas of the lung (four of five cell lines); and small cell carcinomas of the lung (zero of three cell lines). Prostaglandins E2 and F2 alpha were the only prostanoids synthesized in detectable quantities. Prostaglandin E2 biosynthesis (mean +/- SD), pmol/10(6) cells, n = 4) in cell lines exhibiting positive prostaglandin H synthase activity was: LoVo (colorectal adenocarcinoma, 0.4 +/- 0.1); A2780 (ovarian adenocarcinoma, 1.3 +/- 0.3); NCI-H322 (bronchioloalveolar cell carcinoma, 8.4 +/- 3.1); NCI-H358 (bronchioloalveolar cell carcinoma, 7.8 +/- 2.4); EKVX (adenocarcinoma of the lung, 21.3 +/- 5.5); and A427 (large cell undifferentiated carcinoma of the lung, 12.6 +/- 2.8). Prostaglandin F2 alpha production (pmol/10(6) cells +/- SD) was: LoVo (0.3 +/- 0.1); NCI-H322 (0.6 +/- 0.2); NCI-H358 (0.4 +/- 0.1); EKVX (1.8 +/- 0.4); and A427 (11.1 +/- 3.1). These findings suggest that within certain limitations cultured tumor cells provide simplified experimental systems for determination of prostaglandin biosynthetic characteristics of human tumors and that prostanoid biosynthesis may be particularly characteristic of certain non-small cell carcinomas of the lung.

1987

Miller, LH, Sakai RK, Romans P, Gwadz RW, Kantoff P, Coon HG.  1987.  Stable integration and expression of a bacterial gene in the mosquito Anopheles gambiae., 1987 Aug 14. Science (New York, N.Y.). 237(4816):779-81. Abstract

Foreign DNA was successfully introduced into the germline of the African mosquito vector of malaria Anopheles gambiae. Stable integration of genes into the germlines of insects had been achieved previously only in Drosophila melanogaster and related species and required the use of the P element transposon. In these experiments with Anopheles gambiae, the plasmid pUChsneo was used, which contains the selectable marker neo gene flanked by P element inverted repeats. Mosquitoes injected with this plasmid were screened for resistance to the neomycin analog G-418. A single event of plasmid insertion was recovered. Integration appears to be stable and, thus far, resistance to G-418 has been expressed for eight generations. The transformation event appears to be independent of P.

Woo, PT.  1987.  Cryptobia and cryptobiosis in fishes., 1987. Advances in parasitology. 26:199-237.

1979

Cavaillon, JM, Udupa TN, Chou CT, Cinader B, Haeffner-Cavaillon N, Dubiski S.  1979.  Rabbit B spleen lymphocytes and T helper cells. I. Responsiveness to mitogens of B cell subpopulations of different sedimentation velocities and subpopulations bearing or lacking Fcgamma receptors., 1979 Nov. Journal of immunology (Baltimore, Md. : 1950). 123(5):2231-8. Abstract

The response to anti-allotype (anti-Ab4), Nocardia Water Soluble Mitogen (NWSM), pneumococcal polysaccharide type III (SSS III), and human Fc fragments of various purified and unfractionated rabbit spleen cell populations was determined in terms of 3H-thymidine up-take. B cells were isolated either from untreated suspensions of spleen cells or from suspensions from which adherent and phagocytic cells were removed. The purification factor was greater than the enhancement of 3H-thymidine uptake by anti-Ab4, NWSM, and SSS III as compared with the response of unfractionated spleen cells. It thus appears that a helper cell was involved: the mitogen response of purified B cells was enhanced by the addition of T cells. B subpopulations were separated by sedimentation or by rosetting, which allowed us to separate Fcgamma receptor-bearing cells from cells that did not possess this receptor. There were differences between cells responding to B mitogens not only in sedimentation velocity but also in the absolute number of cells. B cells bearing the Fcgamma receptor were less responsive to anti-Ab4 and more responsive to SSS III, NWSM, and human Fc than were B cells lacking the Fcgamma receptor.

1976

Roseleur, OJ, van Gent CM.  1976.  Alkaline and enzymatic hydrolysis of conjugated bile acids., 1976 Jan 16. Clinica chimica acta; international journal of clinical chemistry. 66(2):269-72.
Raffle, A, Gray J, MacDonald HR.  1976.  Letter: First-aid treatment of poisoning., 1976 Jan 10. British medical journal. 1(6001):93.
Mosin, VI, Radbil' OS.  1976.  [Cyclic nucleotides and intestinal function]., 1976 Oct. Klinicheskaia meditsina. 54(10):23-8.
Zegers, PV, Harmet KH, Hanzely L.  1976.  Inhibition of IAA-induced elongation in Avena coleoptile segments by lead: a physiological and an electron microscopic study., 1976. Cytobios. 15(57):23-35. Abstract

A high resolution growth measuring apparatus was used to demonstrate the inhibition of auxin-induced cell elongation in oat coleoptile segments (Avena sativa L. var Holden) by lead at concentrations ranging from 2 x 10-6 M to 2 x 10-3 M. The inhibition was immediate, having no measurable lag period. Electron micrographs of lead-treated and control segments revealed that in the treated material, lead became localized as electron-dense granules in the cell walls and in vesicles associated with dictyosomes. These granules were found to be lead hydroxide phosphate by electron diffraction techniques. The possible significance of this localization and identification with regard to phosphatase activity is discussed.

Silverstein, E, Friedland J, Lyons HA, Gourin A.  1976.  Markedly elevated angiotensin converting enzyme in lymph nodes containing non-necrotizing granulomas in sarcoidosis., 1976 Jun. Proceedings of the National Academy of Sciences of the United States of America. 73(6):2137-41. Abstract

Sarcoidosis is a disease of unknown etiology that is characterized by the generalized formation of granulomas and is accompanied by elevation in the serum in less than half the patients of angiotensin converting enzyme, a dipeptidyl carboxypeptidase that catalyzes the conversion of the decapeptide, angiotensin I, to the pressor octapeptide, angiotensin II, and L-histidyl-L-leucine. Mean activity of angiotensin converting enzyme was elevated generally more than 10-fold in granuloma-containing lymph nodes, but not in lung in which normally it is abundant, in 19 of 20 patients with sarcoidosis. Angiotensin converting enzyme in lymph nodes from subjects with sarcoidosis was similar to the enzyme from normal lung and lymph node with respect to activity as a function of pH, inhibition of activity by EDTA and o-phenanthroline, gel filtration on Sephadex G-200, and requirement for chloride for activity, but appeared to be more heat labile. The data suggest that the granulomas in sarcoidosis may be the source of the elevated serum enzyme and that cells of the granulomas, particularly the epitheloid cells which appear by electron microscopy to have active protein biosynthesis, may be actively synthesizing the enzyme.

Mayes, KR, Holdich DM.  1976.  The water content of muscle and cuticle of the woodlouse Oniscus asellus in conditions of hydration and desiccation., 1976. Comparative biochemistry and physiology. A, Comparative physiology. 53(3):253-8.
Berg, CP, Rodden FA.  1976.  Purification of D-amino oxidase from Trigonopsis variabilis., 1976 Mar. Analytical biochemistry. 71(1):214-22.
Belaich, A, Belaich JP.  1976.  Microcalorimetric study of the anaerobic growth of Escherichia coli: growth thermograms in a synthetic medium., 1976 Jan. Journal of bacteriology. 125(1):14-8. Abstract

A microcalorimetric technique was used for studying the growth of Escherichia coli during anaerobiosis. The growth thermograms obtained are complex and the shape of curves is dependent on the hydrogen lyase activity of the cells. Fermentation balances are given for different culture conditions, and simple growth thermograms are obtained when the hydrogen lyase activity is inhibitied.

1975

Heap, RB.  1975.  Prostaglandins in pyometrial fluid from the cow, bitch and ferret., 1975 Dec. British journal of pharmacology. 55(4):515-8. Abstract

1 Pyometra is a disorder of the uterus usually associated with bacterial infection plus obstruction. 2 Large quantities of fluid often collect in the uterus during this condition. 3 Pyometrial fluid obtained from three species was found to contain prostaglandin F2alpha, usually in large quantities. 4 Prostaglandin E2 was present in smaller quantities in five of the six samples. 5 These findings are discussed in relation to the known occurrence of prostaglandins in inflammatory fluid, and to the problem of infertility.

Höhndorf, H.  1975.  [The accident-injured foot in occupational life]., 1975 Feb. Beiträge zur Orthopädie und Traumatologie. 22(2):104-6.
Smith, RC, Stricker CM.  1975.  Nucleosides and nucleotides of the cold acid-soluble portion of the blood of steers., 1975 Dec. Journal of animal science. 41(6):1674-8.
Sinelnikova, EM, Dvoretskova TV, Kagan ZS.  1975.  [Intermediate plateaux in kinetics of the reaction catalyzed by biodegradative L-threonine dehydratase from Escherichia coli]., 1975 May-Jun. Biokhimii͡a (Moscow, Russia). 40(3):645-51. Abstract

It has been shown that for the reaction catalyzed by "biodegradative" L-threonine dehydratase from E. coli strains K-12 and 980 in 0.5 M phosphate-carbonate buffer, pH 8.4 and pH 9.5, the plots of initial reaction rate (v) versus the initial substrate concentration ([S]0 are characterized by several inflection points, i. e. an intermediate plateau. The plot of v versus the allosteric activator (AMP) concentration have very complicated shapes: there are several inflection points, and also the maximum at L-threonine concentration equal to 3-10(2) and 5-10(-2) M. High AMP concentrations inhibit the enzyme at high substrate concentrations. The reduced glutathion dose not influence the enzyme and does not alter the activating effect of AMP. On the basis of the data obtained it is proposed that the substrate and AMP shift the equilibrium between multiple oligomeric enzyme forms differing in catalytic activity and kinetic manifestations of allosteric interactions between the active and allosteric AMP-binding sites towards polymerization. Thus, the functioning the enzyme under study is discussed in the frames of the model of dissociating regulatory enzymes with multiple intermediate oligomeric forms.

Elgart, ES, Gusovsky T, Rosenberg MD.  1975.  Preparation and characterization of an enzymatically active immobilized derivative of myosin., 1975 Nov 20. Biochimica et biophysica acta. 410(1):178-92. Abstract

Purified skeletal muscle myosin (EC 3.6.1.3) has been covalently bound to Sepharose 4B by the cyanogen bromide procedure. The resulting complex, Sepharose-Myosin, possesses adenosine triphosphatase activity and is relatively stable for long periods of time. Under optimal binding conditions, approximately 33% of the specific ATPase activity of the bound myosin is retained. Polyacrylamide gel electrophoresis of polypeptides released from denatured Sepharose-Myosin indicates that 85% of the myosin is attached to the agarose beads through the heavy chains and the remainder through the light chains, in agreement with predictions of binding and release based upon either the lysine contents or molecular weights of themyosin subunits. The adenosine triphosphatase of the immobilized myosin has been investigated under conditions of varying pH, ionic strength, and cation concentration. The ATPase profiles of immobilized myosin are quite similar to those for free myosin, however subtle differences are found. The Sepharose-Myosin ATPase is not as sensitive as myosin to alterations in salt concentration and the apparent KM is approximately two-fold higher than that of myosin. These differences are probably due to chemical modification in the region of the attachment site(s) to the agarose beads and hydration and diffusion limitations imposed by the polymeric agarose matrix.

Nieto, M, Muñoz E, Carreira J, Andreu JM.  1975.  Conformational and molecular responses to pH variation of the purified membrane adenosine triphosphatase of Micrococcus lysodeikticus., 1975 Dec 16. Biochimica et biophysica acta. 413(3):394-414. Abstract

A preparation of ATPase from the membranes of Micrococcus lysodeikticus, solubilized and more than 95% pure, showed two main bands in analytical polyacrylamide gel electrophoresis. They did not correspond to isoenzymes because one band could be converted into the other by exposure to a mildly alkaline pH value. The conversion was paralleled by changes in molecular weight, circular dichroism and catalytic properties. Denaturation by pH at 25 degrees C was followed by means of circular dichroism, ultracentrifugation and polyacrylamide gel electrophoresis. A large conformational transition took place in the acid range with midpoints at about pH = 3.6 (I = 10(-4) M), 4.3 (I = 0.03 M) and 5.3 (I = 0.1 M). The transition was irreversible. Strong aggregation of the protein occurred in this range of pH. The final product was largely random coil, but even at pH 1.5 dissociation into individual subunits was not complete. However, partial dissociation took place at pH 5 (I = 0.028 M). At this pH value the enzyme was inactive, but 20-30% of the activity could be recovered when the pH was returned to 7.5. In the alkaline region the midpoint of the transition occurred near pH = 11 (I = 0.028 M). The pK of most of the tyrosine residues of the protein was about 10.9. The unfolding was irreversible and the protein was soon converted into peptide species with molecular weights lower than those determined for the subunits by gel electrophoresis in the presence of sodium dodecyl sulphate. Conventional proteolysis did not account for the transformation.

Shanmugam, KT, Chan I, Morandi C.  1975.  Regulation of nitrogen fixation. Nitrogenase-derepressed mutants of Klebsiella pneumoniae., 1975 Nov 11. Biochimica et biophysica acta. 408(2):101-11. Abstract

1. A new procedure is described for selecting nitrogenase-derepressed mutants based on the method of Brenchley et al. (Brenchley, J.E., Prival, M.J. and Magasanik, B. (1973) J. Biol. Chem. 248, 6122-6128) for isolating histidase-constitutive mutants of a non-N2-fixing bacterium. 2. Nitrogenase levels of the new mutants in the presence of NH4+ were as high as 100% of the nitrogenase activity detected in the absence of NH4+. 3. Biochemical characterization of these nitrogen fixation (nif) derepressed mutants reveals that they fall into three classes. Three mutants (strains SK-24, 28 and 29), requiring glutamate for growth, synthesize nitrogenase and glutamine synthetase constitutively (in the presence of NH4+). A second class of mutants (strains SK-27 and 37) requiring glutamine for growth produces derepressed levels of nitrogenase activity and synthesized catalytically inactive glutamine synthetase protein, as determined immunologically. A third class of glutamine-requiring, nitrogenase-derepressed mutants (strain SK-25 and 26) synthesizes neither a catalytically active glutamine synthetase enzyme nor an immunologically cross-reactive glutamine synthetase protein. 4. F-prime complementation analysis reveals that the mutant strains SK-25, 26, 27, 37 map in a segment of the Klebsiella chromosome corresponding to the region coding for glutamine synthetase. Since the mutant strains SK-27 and SK-37 produce inactive glutamine synthetase protein, it is concluded that these mutations map within the glutamine synthetase structural gene.

Kimelberg, HK.  1975.  Alterations in phospholipid-dependent (Na+ +K+)-ATPase activity due to lipid fluidity. Effects of cholesterol and Mg2+., 1975 Nov 17. Biochimica et biophysica acta. 413(1):143-56. Abstract

The (Na+ +K+)-activated, Mg2+-dependent ATPase from rabbit kidney outer medulla was prepared in a partially inactivated, soluble form depleted of endogenous phospholipids, using deoxycholate. This preparation was reactivated 10 to 50-fold by sonicated liposomes of phosphatidylserine, but not by non-sonicated phosphatidylserine liposomes or sonicated phosphatidylcholine liposomes. The reconstituted enzyme resembled native membrane preparations of (Na+ +K+)-ATPase in its pH optimum being around 7.0, showing optimal activity at Mg2+:ATP mol ratios of approximately 1 and a Km value for ATP of 0.4 mM. Arrhenius plots of this reactivated activity at a constant pH of 7.0 and an Mg2+: ATP mol ratio of 1:1 showed a discontinuity (sharp change of slope) at 17 degrees C, with activation energy (Ea) values of 13-15 kcal/mol above this temperature and 30-35 kcal below it. A further discontinuity was also found at 8.0 degrees C and the Ea below this was very high (greater than 100 kcal/mol). Increased Mg2+ concentrations at Mg2+:ATP ratios in excess of 1:1 inhibited the (Na+ +K+)-ATPase activity and also abolished the discontinuities in the Arrhenius plots. The addition of cholesterol to phosphatidylserine at a 1:1 mol ratio partially inhibited (Na+ +K+)-ATPase reactivation. Arrhenius plots under these conditions showed a single discontinuity at 20 degrees C and Ea values of 22 and 68 kcal/mol above and below this temperature respectively. The ouabain-insensitive Mg2+-ATPase normally showed a linear Arrhenius plot with an Ea of 8 kcal/mol. The cholesterol-phosphatidylserine mixed liposomes stimulated the Mg2+-ATPase activity, which now also showed a discontinuity at 20 degrees C with, however, an increased value of 14 kcal/mol above this temperature and 6 kcal/mol below. Kinetic studies showed that cholesterol had no significant effect on the Km values for ATP. Since both cholesterol and Mg2+ are known to alter the effects of temperature on the fluidity of phospholipids, the above results are discussed in this context.

Zemek, J, Bílik V, Zákutná L.  1975.  Effect of some aldoses on growth of Saccharomyces cerevisiae inhibited with molybdenum., 1975. Folia microbiologica. 20(6):467-9. Abstract

The inhibitory effect of molybdenum ions on growth of yeasts at pH 5.5 was found to be decreased by aldoses in the following order: D-talose greater than L-mannose greater than L-ribose greater than D-lyxose greater than L-galactose greater than L-arabinose greater than L-glucose greater than L-xylose. Increased concentrations of molybdenum brought about morphological changes of yeast cells. Cells grown under these conditions were smaller, had thicker walls and formed clusters.

Nitta, K, Yoneyama M.  1975.  Polymer concentration dependence of the helix to random coil transition of a charged polypeptide in aqueous salt solution., 1975 Oct. Biophysical chemistry. 3(4):323-9. Abstract

The helix to coil transition of poly(L-glutamic acid) was investigated in 0.05 and 0.005 M aqueous potassium chloride solutions by use of potentiometric titration and circular dichroism measurement. Polymer concentration dependence of the transition was observed in the range from 0.006 to 0.04 monomol/e in 0.005 M KG1 solution. The polymer concentration dependence can be interpreted by current theories of the transition of charged polypeptides and of titration curves of linear weak polyelectrolytes taking the effect of polymer concentration into consideration.

Thompson, RJ.  1975.  The formation of CDP-diglyceride by isolated neuronal nuclei., 1975 Dec. Journal of neurochemistry. 25(6):811-23.
Greenwood, RD.  1975.  Digitalis as treatment for pulmonary comsumption, 1799., 1975 Nov. IMJ. Illinois medical journal. 148(5):531.
Dawson, RM.  1975.  The reaction of choline and 3,3-dimethyl-1-butanol with the acetylenzyme from acetylcholinesterase., 1975 Dec. Journal of neurochemistry. 25(6):783-7.
Coscia, L, Causa P, Giuliani E, Nunziata A.  1975.  Pharmacological properties of new neuroleptic compounds., 1975 Sep. Arzneimittel-Forschung. 25(9):1436-42. Abstract

RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level.

Mitchell, B, Haigis E, Steinmann B, Gitzelmann R.  1975.  Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture., 1975 Dec. Proceedings of the National Academy of Sciences of the United States of America. 72(12):5026-30. Abstract

Stimulation with phytohemagglutinin of the leukocytes from six of the seven known individuals with UDP-galactose 4-epimerase (= UDP-glucose 4-epimerase; EC 5.1.3.2) deficiency consistently resulted in the appearance of epimerase activity in the cultured cells. A long-term lymphoblast culture derived from one proband also contained an active epimerase enzyme. A comparison of the properties of this enzyme with those of epimerase produced by control lymphoblast lines revealed comparable Km values for UDP-galactose and NAD and identical behavior on polyacrylamide electrophoresis. However, a difference in the NAD requirement for heat stability at 40 degree provided some evidence for a structural defect in this enzyme. Possible explanations for the appearance of UDP-galactose 4-epimerase activity in stimulated lymphocytes include an increased rate of synthesis of a mutant enzyme and a derepression of an epimerase locus during lymphocyte transformation.

Lorkin, PA, Stephens AD, Beard ME, Wrigley PF, Adams L, Lehmann H.  1975.  Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia., 1975 Oct 25. British medical journal. 4(5990):200-2. Abstract

A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident.

UoN Websites Search