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Biomedical subjects

M B Murray

Publications and source records attributed to M B Murray.

At least 19 recordsLinked to original sources
PubMed2006

Frequency and implications of pyrazinamide resistance in managing previously treated tuberculosis patients.

OBJECTIVE: To determine the extent of pyrazinamide (PZA) resistance in isolates from previously treated patients from the Western Cape, South Africa. DESIGN: Drug-resistant isolates, isolates resistant to one or more drugs other than PZA (PZA resistance is not routinely determined) (n = 127), and drug-susceptible (n = 47) clinical isolates of Mycobacterium tuberculosis from previously treated patients from the Western Cape were phenotypically (BACTEC MGIT 960) and genotypically (pncA gene sequencing) analysed for PZA resistance. RESULTS: MGIT analysis found that 68 of the 127 drug-resistant isolates were PZA-resistant. Nearly all (63/68) PZA-resistant isolates had diverse nucleotide changes scattered throughout the pncA gene, and five PZA-resistant isolates had no pncA mutations. Of the 47 phenotypically susceptible isolates, 46 were susceptible to PZA, while one isolate was PZA-monoresistant (OR = 53.0, 95% CI = 7.1-396.5). A pncA polymorphism (Thr114Met) that did not confer PZA resistance was also identified. PZA resistance was strongly associated with multidrug-resistant tuberculosis (MDR-TB). CONCLUSION: An alarmingly high proportion of South African drug-resistant M. tuberculosis isolates are PZA-resistant, indicating that PZA should not be relied upon in managing patients with MDR-TB in the Western Cape. A method for the rapid detection of PZA resistance would be beneficial in managing patients with suspected drug resistance.

Antitubercular Agents↗
PubMed2006

Causes of death during tuberculosis treatment in Tomsk Oblast, Russia.

SETTING: Tuberculosis (TB) incidence and mortality in Russia have risen dramatically over the past 15 years. OBJECTIVE: To identify risk factors and causes of death among TB patients in Russia. DESIGN: A retrospective study conducted to determine the risk factors and causes of death in patients receiving TB therapy in Tomsk, Siberia. RESULTS: Of 1916 patients who initiated treatment between 1 January 2002 and 31 December 2003, 183 (9.6%) died during treatment, 38 (21%) in the first week of therapy. Twenty-five per cent of deaths were not directly attributable to TB. Risk factors for death included older age, previous treatment for TB, multidrug resistance and alcoholism. CONCLUSIONS: The high death rate during TB treatment observed in this cohort likely reflects an increased risk of dying not only from TB, but also from comorbid conditions, such as alcoholism and cardiovascular disease. Overall, alcoholism and late presentation both contributed substantially to the mortality in this cohort.

Adult↗
PubMed2002

Lignification in beech (Fagus sylvatica) grown at elevated CO2 concentrations: interaction with nutrient availability and leaf maturation.

Beech (Fagus sylvatica L.) seedlings were grown in an ambient or elevated CO2 concentration ([CO2]) either in small stands in microcosms for three to four seasons or individually in pots fertilized at different nutrient supply rates. Leaves at different stages of development, as well as stems and roots at the end of the growing season, were used for analysis of structural biomass and lignin. In elevated [CO2], lignification of leaves was slightly retarded compared with structural biomass production and showed a strong correlation with the activities of ionically, cell-wall-bound peroxidases but not with total soluble peroxidases or covalently wall-bound peroxidases. The effect of elevated [CO2] on lignin concentration of mature tissues was dependent on nutrient supply rate. In leaves and roots, elevated [CO2] increased the lignin concentration in dry mass in N-limited plants. In seedlings grown with high nutrient supply, the lignin concentration in dry mass was unaffected or diminished by elevated [CO2]. Because elevated [CO2] enhanced seedling growth in the high nutrient supply treatments, the total amount of lignin produced per seedling was higher in these treatments. We predict that long-term sequestration of carbon will increase as long as biomass production is stimulated by elevated [CO2] and that tissue quality will change depending on developmental stage and nutrient availability.

Biomass↗
PubMed1998

Structure-function studies of ligand-induced epidermal growth factor receptor dimerization.

We present a novel 96-well assay which we have applied to a structure-function study of epidermal growth factor receptor dimerization. The basis of the assay lies in the increased probability of EGFRs being captured as dimers by a bivalent antibody when they are immobilized in the presence of a cognate ligand. Once immobilized, the antibody acts as a tether, retaining the receptor in its dimeric state with a resultant 5-7-fold increase in binding of a radiolabeled ligand probe. When the assay was applied to members of the EGF ligand family, murine EGF, transforming growth factor alpha, and heparin-binding EGF-like growth factor were comparable with human EGF (EC50 = 2nM); betacellulin, which has a broader receptor specificity, was slightly less effective. In contrast, amphiregulin (AR1-84), which has a truncated C-tail and lacks a conserved leucine residue, was ineffective unless used at >1 microM. We further probed the involvement of the C-tail and the conserved leucine residue in receptor dimerization by comparing the activities of two genetically modified EGFs (the chimera mEGF/TGFalpha44-50 and the EGF point mutant L47A) and a C-terminally extended form of AR (AR1-90) with those of two other unrelated EGF mutants (I23T and L15A). The potency of these ligands was in the order EGF > I23T > mEGF/TGFalpha44-50 > L47A = L15A >> AR1-90 > AR1-84. Although AR was much worse than predicted from its affinity, this defect could be partially rectified by co-localization of the immobilizing antibody with heparin. Thus, it seems likely that AR cannot dimerize the EGFR unless other accessory molecules are present to stabilize its functional association with the EGFR.

Cell Line↗
PubMed1998

Structure-function analysis of a conserved aromatic cluster in the N-terminal domain of human epidermal growth factor.

The importance of a cluster of conserved aromatic residues of human epidermal growth factor (hEGF) to the receptor binding epitope is suggested by the interaction of His10 and Tyr13 of the A-loop with Tyr22 and Tyr29 of the N-terminal beta-sheet to form a hydrophobic surface on the hEGF protein. Indeed, Tyr13 has previously been shown to contribute a hydrophobic determinant to receptor binding. The roles of His10, Tyr22 and Tyr29 were investigated by structure-function analysis of hEGF mutant analogues containing individual replacements of each residue. Substitutions with aromatic residues or a leucine at position 10 retained receptor affinities and agonist activities similar to wild-type indicating that an aromatic residue is not essential. Variants with polar, charged or aliphatic substitutions altered in size and/or hydrophobicity exhibited reduced binding and agonist activities. 1-Dimensional 1H NMR spectra of high, moderate and low-affinity analogues at position 10 suggested only minor alterations in hEGF native structure. In contrast, a variety of replacements were tolerated at position 22 or 29 indicating that neither aromaticity nor hydrophobicity of Tyr22 and Tyr29 is required for receptor binding. CD spectra of mutant analogues at position 22 or 29 indicated a correlation between loss of receptor affinity and alterations in hEGF structure. The results indicate that similar to Tyr13, His10 of hEGF contributes hydrophobicity to the receptor binding epitope, whereas Tyr22 and Tyr29 do not appear to be directly involved in receptor interactions. The latter conclusion, together with previous studies, suggests that hydrophobic residues on only one face of the N-terminal beta-sheet of hEGF are important in receptor recognition.

Circular Dichroism↗
PubMed1995

Infections during severe primary undernutrition and subsequent refeeding: paradoxical findings.

BACKGROUND: Our earlier uncontrolled observations during primary famine and subsequent refeeding did not suggest that severe undernutrition inevitably increases vulnerability to infection. Some infections appeared suppressed by famine but reactivated by refeeding. AIMS: To examine prospectively the occurrence of infections in a large cohort of primary famine victims before and during refeeding. METHODS: From 1973 to 1993, 4382 famine victims aged 14 or more with an estimated weight loss greater than 25% were weighed and examined for infection before and after one, two, three and four weeks of refeeding. In 137, serum C-reactive protein was measured in an effort to detect latent asymptomatic infections before and after two weeks of refeeding. Refeeding diets included wheat, sorghum, millet, ghee and milk powder. RESULTS: Mean weight loss +/- SD was 28.7 +/- 2.3%. Before refeeding overt infections were found in 4.9%, an incidence rising to 29.1% at two weeks of refeeding and declining after four. Those developing infections gained more weight at two weeks, 4.6 3 +/- 0.81 kg, than those never infected, 3.94 +/- 0.76 (p = < 0.001 t test). C-reactive protein levels confirmed the presence of latent infections before refeeding. CONCLUSIONS: Severe undernutrition can suppress certain infections, mostly those due to intracellular pathogens and especially P. falciparum. Refeeding reactivates suppressed infection and can increase vulnerability to certain new infections especially of viral origin. Those gaining weight the most rapidly may be at greatest risk. Refeeding with foods alien to local culture could play a role in reactivating latent infections. Our findings may be limited to severe undernutrition and not apply to lesser forms or secondary undernutrition in hospital patients. These studies were done during charitable provision of medical care to famine victims.

Adolescent↗
PubMed1993

The impact of constituent ions of acid mist on assimilation and stomatal conductance of Norway spruce prior and post mid-winter freezing.

Norway spruce seedlings were sprayed twice weekly with one of a range of artificial mists at either pH 2.5, 3.0 or 5.6, for three months. The mists consisted of either (NH4)2SO4 (pH 5.6), NH4NO3 (pH 5.6), water (pH 5.6), HNO3 (pH 2.5), H2SO4 (pH 2.5). In late December 1988 and early January 1989 the light response of assimilation and stomatal conductance were assessed in the laboratory following a 4-day equilibration period at 12 degrees C. The intact trees were then subjected to a mild (-10 degrees C), brief (3 h) frost in the dark and the recovery of light saturated assimilation (Amax) was followed during the subsequent light period. The same trees were then subjected to a second 3 h (-18 degrees C) frost. The recovery of Amax during the next day was followed. All ion-containing mists stimulated Amax and apparent quantum yield relative to control trees, irrespective of pH. The mists containing SO4 made stomatal conductance unresponsive to light flux density and caused the stomata to lock open. Frosts of -10 degrees C and -18 degrees C did not inhibit the Amax of control trees for longer than 200 min into the light period. In contrast, the ion-containing mists exerted a significant inhibitory effect upon the recovery of Amax. Nitric acid inhibited Amax to 35% of the pre-frost value, whilst the remaining treatments inhibited Amax between 15% and 40% of the pre-frost value. It is concluded that SO4 causes increased mid-winter frost sensitivity and NO3 ameliortes this effect. The results are discussed in relation to forest decline.

Journal Article↗
PubMed1992

Leadership attributes identified by practicing occupational health nurses.

This study examined which theoretical approaches to leadership occupational health nurses perceive as most desirable. The trait approach dominates in North American research literature, with occupational health nurses favoring the more traditional leadership attributes of "visionary," "intellectually creative," and "strong linguistic ability." Australian occupational health nurses identified the managerial character traits of "being well informed," "good communication skills," and "objective decision maker" as most appropriate traits of good leaders. Occupational health nurses need to develop alternative leadership approaches to acquire effective political and organizational strategies in today's competitive environment.

Attitude of Health Personnel↗
PubMed1991

HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies.

We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study. To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles. Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p less than 0.005). A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls). HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p less than 0.005; relative risk, 6.1; etiologic fraction, 0.22). We identified the combined DR4-DQw4 haplotype in five of 41 Caucasian IDC patients (12%) and none of 53 controls (p less than 0.007). A comparison of specific antigen frequencies between the preliminary and validation studies did not reveal significant differences; therefore, the data from the two studies were examined in combination. For the combined studies, DR4 was elevated (51% versus 27% in controls, p less than 0.001), and DRw6 was decreased (9% versus 24% in controls, p less than 0.01). The relative risk for DR4 was 2.8, and the etiologic fraction was 0.33.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Dilated↗
PubMed1990

Identification of multiple thyroid hormone response elements located far upstream from the rat S14 promoter.

Expression of the rat gene designated S14 is rapidly and markedly induced by 3,3',5-triiodo-L-thyronine (T3) in the liver. We have used nuclear run-on assays and transfection studies to explore the basis of this regulation. These studies indicate that T3 induction of hepatic S14 mRNA is due primarily, if not exclusively, to changes in the rate of gene transcription. Both alpha and beta forms of the thyroid hormone receptor (c-erbA) can activate S14 promoter activity in a co-transfection assay. This activation occurs in a dose-dependent manner and requires the expression of the T3 receptor from transfected cDNA in either COS-1 cells or primary rat hepatocytes. Delineation of sequences essential for control of S14 promoter activity indicates that multiple thyroid hormone response elements (TREs) are involved. These TREs have been localized in the far upstream 5'-flanking region of the S14 gene, approximately 2.7 kilobases from the S14 transcriptional initiation site. DNA-binding studies with in vitro translated c-erbA indicate that each of the S14 TREs contains a specific binding site for the receptor. The location of the S14 TREs far upstream from the promoter site may necessitate the presence of multiple TREs for hormonal responsiveness.

Animals↗
PubMed1989

Identification of nuclear factors that enhance binding of the thyroid hormone receptor to a thyroid hormone response element.

Using a gel shift assay, we analyzed the binding of in vitro translated alpha- and beta-thyroid hormone (T3) receptors to a T3-response element (TRE) derived from the rat GH gene. No receptor-TRE complexes were observed when translated receptor alone was incubated with the TRE. However, addition of a nuclear extract from liver to the translational products resulted in the formation of two receptor-DNA complexes for both the alpha- and beta-receptors. These complexes were shown to contain translated receptor by comigration of 32P-labeled TRE and 35S-labeled receptor in the gel shift assay. A competition experiment demonstrated that formation of the complexes was sequence specific. Preincubation of the liver nuclear extract at 60 C abolished formation of both complexes indicating that receptor-TRE binding required a heat-labile nuclear factor. Phosphocellulose chromatography of the nuclear extract resulted in separation of the activities required for formation of the two complexes. Analysis of nuclear extracts from different tissues revealed that one complex formed in the presence of all extracts, whereas the second complex appeared predominantly with a nuclear extract from liver. Addition of T3 to the binding reaction had no effect on receptor-TRE complex formation. We suggest that nuclear factors interact with the T3 receptor to enhance hormone-independent binding to a TRE.

Binding, Competitive↗
PubMed1988

Isolation and characterization of rat cDNA clones for two distinct thyroid hormone receptors.

Two distinct v-erbA-related cDNA clones representing the products of different genes were isolated from a rat liver cDNA library. The first, rc-erbA-alpha, was 82% identical to v-erbA and encoded a polypeptide with a calculated molecular mass of 45,000 daltons. This cDNA clone arises from the same gene product as a v-erbA-related cDNA isolated from rat brain by Thompson et al. (Thompson, C. C., Weinberger, C., Lebo, R., and Evans, R. (1987) Science 237, 1610-1614). The second cDNA clone, rc-erbA-beta, was 76% identical to v-erbA and encoded a polypeptide with a calculated molecular mass of 52,000 daltons. Both rc-erbA-alpha and rc-erbA-beta translational products bound 3,5,3'-triiodo-L-thyronine with affinities equal to each other (Kd approximately equal to 0.4 nM) and comparable to the nuclear thyroid hormone receptor extracted from rat liver. The relative affinities of a series of thyroid hormone analogs for both translational products were also identical. In various tissues and cell lines, the relative levels of rc-erbA-beta RNA, but not rc-erbA-alpha RNA, correlated with measurements of nuclear 3,5,3'-triiodo-L-thyronine binding sites. Based on this correlation, we suggest that rc-erbA-beta may encode the "classical" nuclear thyroid hormone receptor, whereas rc-erbA-alpha may encode an isoreceptor species with differing functional properties.

Amino Acid Sequence↗
PubMed1988

Diameters and dry weights of tree shoots: effects of Young's modulus, taper, deflection and angle.

The structural theory for cantilever beams was used to calculate the diameters and dry weights of wood that unbranched shoots must produce to support their own weights. The study was done on Picea sitchensis (Bong.) Carr., Pinus contorta Dougl., Larix decidua Mill. and Betula pendula Roth. syn. verrucosa Ehrh. The weights of wood increased in a non-linear fashion with increase in shoot length. A large investment in wood (as measured by diameter and dry weight) was required to maintain a small endpoint deflection (1-5% of the length). By contrast, the degree of linear taper had only a small effect on support costs, as did the Young's modulus of the wood (over the range 1-4 GPa) and the angle of the shoot from the horizontal (over the range 0-45 degrees ). Current year's shoots on young trees of P. sitchensis and P. contorta incur a high support cost in order to maintain small (1-5%) deflections throughout the year: similar shoots of L. decidua and B. pendula have smaller support costs because they deflect by about 20% after leaf expansion in spring.

Journal Article↗
PubMed1980

Molluscum contagiosum and herpes simplex in Maasai pastoralists; refeeding activation of virus infection following famine?

An epidemic of molluscum contagiosum and oro-genital herpes simplex was observed in Maasai pastoralists of the Rift Valley. It coincided with a period of refeeding following famine, when the relief diet was different from normal milk fare. We propose that refeeding may be an important mechanism for activation of certain viral infections previously suppressed by famine.

Adolescent↗
PubMed1978

The adverse effect of iron repletion on the course of certain infections.

The incidence of infections was studied in 137 iron-deficient Somali nomads, 67 of whom were treated with placebo and 71 with iron. Seven episodes of infection occurred in the placebo group and 36 in the group treated with iron; these 36 episodes included activation of pre-existing malaria, brucellosis, and tuberculosis. This difference suggested that host defence against these infections was better during iron deficiency than during iron repletion. Iron deficiency among Somali nomads may be part of an ecological compromise, permitting optimum co-survival of host and infecting agent.

Adolescent↗
PubMed1978

Serum cholesterol, triglycerides and heart disease of nomadic and sedentary tribesmen consuming isoenergetic diets of high and low fat content.

1. The effects were examined of two approximately isoenergetic diets differing widely in saturated fat content on the levels of serum cholesterol and triglycerides of nomads and non-nomads in eastern Niger. Each person was also examined for clinical and electrocardiographic evidence of heart disease. 2. No significant differences could be found between serum cholesterol and triglyceride levels of 297 Anagamba nomad men consuming 73% energy as fat and 303 Kanouri sedentary men consuming 9% energy as fat. 3. Rheumatic heart disease was common in nomads and four possible cases of ischaemic heart disease were found in sedentary men only.

Adolescent↗
PubMed1978

The effect of iron status of Nigerien mothers on that of their infants at birth and 6 months, and on the concentration of Fe in breast milk.

1. Within the limits of this study, neither maternal iron deficiency nor Fe-overload as measured at term appeared to affect the complement of Fe received by the foetus. 2. Infants feeding entirely on breast milk appeared to have normal Fe status 6 months postpartum regardless of the Fe status of the mother. 3. No relationship could be demonstrated between the Fe content of breast milk and the Fe status of the mother.

Anemia, Hypochromic↗