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Biomedical subjects

J Baldwin

Publications and source records attributed to J Baldwin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pelvic limb musculature in the emu Dromaius novaehollandiae (Aves: Struthioniformes: Dromaiidae): adaptations to high-speed running.

Emus provide an excellent opportunity for studying sustained high-speed running by a bird. Their pelvic limb musculature is described in detail and morphological features characteristic of a cursorial lifestyle are identified. Several anatomical features of the pelvic limb reflect the emus' ability for sustained running at high speeds: (1) emus have a reduced number of toes and associated muscles, (2) emus are unique among birds in having a M. gastrocnemius, the most powerful muscle in the shank, that has four muscle bellies, not the usual three, and (3) contribution to total body mass of the pelvic limb muscles of emus is similar to that of the flight muscles of flying birds, whereas the pelvic limb muscles of flying birds constitute a much smaller proportion of total body mass. Generally, the pelvic limb musculature of emus resembles that of other ratites with the notable exception of M. gastrocnemius. The presence and arrangement of four muscle bellies may increase the effectiveness of M. gastrocnemius and other muscles during cursorial locomotion by moving the limb in a cranio-caudal rather than a latero-medial plane.

Animals↗
PubMed1998

Coexistence of macular corneal dystrophy types I and II in a single sibship.

BACKGROUND: Macular corneal dystrophy (MCD) is an inherited autosomal recessive disorder that has been subdivided into two primary immunophenotypes, MCD types I and II. The MCD type I gene has been localised previously to chromosome 16q22 and suggestive evidence provided that MCD type II gene is also linked to this region. Here an unusual family is reported where both MCD types I and II are found in a single sibship. METHODS: Immunoreactivity to an anti-keratan sulphate monoclonal antibody (5-D-4) was evaluated in patients' serum and in corneal tissue obtained at keratoplasty. Chromosomal haplotypes were constructed using microsatellite repeat markers spanning the region of the MCD type I locus. RESULTS: Immunological studies demonstrated that two of the affected siblings have MCD type II while one has MCD type I. Haplotype analysis suggests that all three affected sibs inherited one identical parental haplotype. However, the two MCD types differ in their alternative chromosome with both MCD type II children sharing an identical haplotype, different from their MCD type I sibling. CONCLUSION: The findings in this study support the hypothesis that the genes for MCD types I and II co-localise to the same region of chromosome 16 and are likely to be due to allelic manifestations of the same abnormal gene.

Aged↗
PubMed1998

Cloning of the Nocardia corallina polyhydroxyalkanoate synthase gene and production of poly-(3-hydroxybutyrate-co-3-hydroxyhexanoate) and poly-(3-hydroxyvalerate-co-3-hydroxyheptanoate).

The polyhydroxyalkanoate (PHA) synthase gene (phaCNc) from Nocardia corallina was identified in a lambda library on a 6-kb BamHI fragment. A 2.8-kb XhoII subfragment was found to contain the intact PHA synthase. This 2.8-kb fragment was subjected to DNA sequencing and was found to contain the coding region for the PHA synthase and a small downstream open reading frame of unknown function. On the basis of DNA sequence, phaCNc is closest in homology to the PHA synthases (phaCPaI and phaCPaII) of Pseudomonas aeruginosa (approximately 41% identity and 55% similarity). The 2.8-kb XhoII fragment containing phaCNc was subcloned into broad host range mobilizable plasmids and transferred into Escherichia coli, Klebsiella aerogenes (both containing a plasmid bearing phaA and phaB from Ralstonia eutropha), and PHA-negative strains of R. eutropha and Pseudomonas putida. The recombinant strains were grown on various carbon sources and the resulting polymers were analyzed. In these strains, the PHA synthase from N. corallina was able to mediate the production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) containing high levels of 3-hydroxyhexanoate when grown on hexanoate and larger even-chain fatty acids and poly(3-hydroxyvalerate-co-3-hydroxyheptanoate) containing high levels of 3-hydroxyheptanoate when grown on heptanoate or larger odd-chain fatty acids.

Acyltransferases↗
PubMed1997

Effects of urea on M4-lactate dehydrogenase from elasmobranchs and urea-accumulating Australian desert frogs.

We measured the effect of urea on M4-lactate dehydrogenase (M4-LDH) from elasmobranchs and Australian desert frogs (urea accumulators) and from two animals that do not accumulate urea, the axolotl and the rabbit. An analysis of the effect of urea on the Kd(NADH), V, V/K(m(prr)) and V/K(m(NADH)) shows that in all cases the major effect of urea was on the binding of pyruvate, which fits with data in the literature that show that urea acts as a competitive inhibitor of LDH. The characteristics of the elasmobranch enzymes are consistent with a proposed adaptation model, but the situation for the enzymes from the aestivating frogs is equivocal. Urea (400 mM) had less effect on the K(m(prr)) of M4-LDH from the urea accumulators than it did on the non-accumulators, suggesting a general adaptation and that the enzyme produced by the aestivating frogs (urea accumulators) is kinetically different from that of non-aestivating frogs (non-accumulators). A new approach is used to characterize the overall pattern of adaptation to urea. The pattern is similar in an enzyme from an elasmobranch and an aestivating frog despite the temporary presence of urea in the latter and the phylogenetic difference between these animals.

Ambystoma↗
PubMed1996

A three-year clinical trial using a glass ionomer cement for the bonding of orthodontic brackets.

Recent clinical studies measuring orthodontic bracket failure, when using glass ionomer cement as an adhesive, have reported a wide range of percentages of bracket failure. The present study recorded bracket failure over a 3-year period, longer than had been previously measured. Seventeen participants were randomly assigned to one of two treatment groups, either using glass ionomer cement or composite resin for bonding. In each group, brackets were bonded to incisors, canines, and premolars. Bracket failure was measured over the duration of comprehensive orthodontic treatment for all participants. Brackets bonded with the glass ionomer cement were more likely to fail (log-rank test; P < or = 0.022). This difference was clinically significant. At the present time, the disadvantage of extra bracket failures appears to outweigh potential advantages when considering glass ionomer cement for the routine bonding of orthodontic brackets.

Adhesives↗
PubMed1996

Peroxynitrite modification of glutathione reductase: modeling studies and kinetic evidence suggest the modification of tyrosines at the glutathione disulfide binding site.

The catalytic properties of glutathione reductase for its substrate, glutathione disulfide, were altered following a 60 s exposure to a 100-fold molar excess of peroxynitrite; the K(M) value was increased by approximately 2.5-fold and the V(max) value was decreased by approximately 1.7-fold. The kinetic alterations are thought to result from nitrotyrosine formation as the intrinsic Tyr fluorescence is diminished. The UV-visible spectrum of glutathione reductase exhibited absorbance at approximately 423 nm, characteristic of nitrotyrosine. In addition, the presence of nitrotyrosine has been detected by Western immunoblots with an anti-nitrotyrosine antibody. The peroxynitrite-induced inactivation is not observed in the presence of excess glutathione disulfide. However, excess NADPH offered no protection against peroxynitrite-induced inactivation. These observations suggest that the modification of approximately 1.8 Tyr per subunit, at or near the glutathione disulfide binding domain, probably results in the observed catalytic alterations. To test this hypothesis, the two tyrosines closest to the glutathione disulfide binding domain (Tyr114 and Tyr106), as indicated by the X-ray crystallographic data [Karplus and Schulz (1989) J. Biol. Chem., 210, 163-180], were each converted to nitrotyrosines by molecular modeling and the structure energy was minimized. These theoretical calculations indicate that the bond lengths between Tyr114-O and the Gly-N and Cys II-N of glutathione disulfide bound to glutathione reductase (Karplus and Schulz, 1989) increased by 3.0 and 4.3 A, respectively, upon nitration. In the case of Tyr106 the 0-Cys II-N distance also increases by approximately 1.6 A. The loss of these hydrogen bonding contacts is likely to result in the observed catalytic alterations upon reaction with peroxynitrite.

Animals↗
PubMed1994

Metabolic development of the sheep diaphragm during fetal and newborn life.

Several parameters indicative of whole muscle aerobic and anaerobic metabolism were compared in heart, diaphragm and two locomotory muscles of sheep (Ovis aries) ranging from 90 days gestation to adult animals. Aerobic metabolism was assessed from myoglobin content, anaerobic metabolism from the pH buffering capacity and the balance between the two from the properties of the lactate dehydrogenase isozymes. We expected the diaphragm and heart, as the two vital pumps of the body, to have substantial aerobic capacity at birth. For the left ventricular myocardium this appears to be true, with the myoglobin level at birth averaging 69% of the adult value. However, the diaphragm had only 15% of the adult myoglobin level, a level similar to that in vastus lateralis and medial gastrocnemius muscles. In the first 18 days postnatally, myoglobin levels in the diaphragm did not change. Anaerobic capacity, as indicated by pH buffering capacity, increased in all four muscles during fetal life, reaching from 69-96% of adult values on day 1 after birth. A rapid increase in pH buffering capacity occurred in all four muscles in the first 6 days postnatally suggesting that anaerobic glycolysis is important to the newborn. We conclude that the work done by the fetal heart leads to the development of a high aerobic capacity by birth, but the activity of the fetal diaphragm does not have this effect.

Aerobiosis↗
PubMed1994

Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds.

Synthesis of influenza virus mRNA is primed by capped and methylated (cap 1, m7GpppXm) RNAs which the virus derives by endonucleolytic cleavage from RNA polymerase II transcripts in host cells. The conserved nature of the endonucleolytic processing provides a unique target for the development of antiviral agents for influenza viruses. A series of 4-substituted 2,4-dioxobutanoic acid compounds has been identified as selective inhibitors of this activity in both influenza A and B viruses. These inhibitors exhibited 50% inhibitory concentrations in the range of 0.2 to 29.0 microM for cap-dependent influenza virus transcription and had no effect on the activity of other viral and cellular polymerases when tested at 100- to 500-fold higher concentrations. The compounds did not inhibit the initiation or elongation of influenza virus mRNA synthesis but specifically inhibited the cleavage of capped RNAs by the influenza virus endonuclease and were not inhibitory to the activities of other nucleases. Additionally, the compounds specifically inhibited replication of influenza A and B viruses in cell culture with potencies comparable to the 50% inhibitory concentrations obtained for transcription.

Animals↗
PubMed1994

OXYGEN TRANSPORT IN MARINE GREEN TURTLE (CHELONIA MYDAS) HATCHLINGS: BLOOD VISCOSITY AND CONTROL OF HEMOGLOBIN OXYGEN-AFFINITY

Erythrocytes from green turtle hatchlings contain a single embryonic component, unlike those from other cleidoic eggs, in which adult hemoglobin (Hb) constitutes a significant fraction of total Hb at hatching. The functional properties of the isolated and purified green turtle hatchling Hb that distinguish it from adult Hb are a high affinity for oxygen and marked sensitivity to organic phosphate modulators. Hatchling erythrocytes also contain higher concentrations of ATP and 2,3-diphosphoglyceric acid, but their oxygen affinity is indistinguishable from that of adult erythrocytes. Hatchling erythrocyte mean cell volume is approximately half of the adult value, but hematocrit, blood hemoglobin concentration and blood viscosity of hatchlings and adults are similar. Oxygen-carrying capacity in green turtles, unlike that of other diving vertebrates, corresponds with a theoretically derived optimum. The possibility of allosteric control of Hb oxygen-binding in hatchlings may relate not to the challenge of exercise during the dispersal phase but to conditions in the late embryo in the nest.

Journal Article↗
PubMed1994

Pre-eclampsia. II: Investigative procedures.

Pre-eclampsia is a potential hazard to both mother and fetus. Clinical features alone give a poor indication of the significance or severity of the condition. Investigations which indicate the extent of multisystem maternal changes help to distinguish pre-eclampsia from other hypertensive disorders and help to assess the need for, and timing of intervention. Serial assessments of sensitive indicators such as proteinuria, platelet counts and serum urate are more helpful than single measurements. Full ultrasound biophysical profiles of the fetus are desirable in the presence of severe pre-eclampsia, but when this sophisticated examination is not available much can be learned from ultrasound estimates of fetal growth, liquor volume and from cardiotocography.

Female↗
PubMed1994

How to gain ethical committee approval.

Research involving NHS patients or premises must have approval of the local research ethical committee (LREC). Allow plenty of time for your application to be processed--find out about dates for submitting applications and the time taken to reach a decision. Follow any written LREC guidelines closely and complete any local forms in full. When making your application, put yourself in the place of your subjects; would you be willing to do what you are asking of them? Make sure that all the relevant questionnaires, letters and other documents accompany your application. If you are asked to attend a meeting, find out in advance what is expected of you.

Ethics Committees↗
PubMed1994

Now we're talking.

Explore the source record for details and available documents.

Attitude to Health↗
PubMed1993

COS-7 cells stably transfected to express the human ETB receptor provide a useful screen for endothelin receptor antagonists.

Endothelin acts via specific membrane-bound receptors through signal transduction pathways that include increases in intracellular free calcium and inositol triphosphate generation. Two endothelin receptors have been cloned. The ETA receptor is ET-1 selective, and the ETB receptor is isopeptide nonselective. Both receptor subtypes are widely distributed throughout the body, although ETA receptors predominate in vascular smooth muscle, whereas ETB receptors predominate in the brain. The presence of mixed receptor subtypes makes functional screening of subtype-specific analogues difficult. A eukaryotic expression vector was constructed by inserting the cloned coding region of the human ETB receptor downstream from the Rous sarcoma promoter. COS-7 cells were transfected with this construct, and cell lines were isolated with stably integrated copies of the relevant gene. One line, 1C7, was shown to specifically bind 125I-ET-1. Scatchard analysis indicated a Kd value of 8.8 pM and a Bmax value of 1.02 pM/mg. ET-1 stimulated phosphoinositide hydrolysis in a dose-dependent manner, as did ET-3, sarafotoxin 6c, and [1,3,13,15Ala]ET-1, whereas BQ123, a selective ETA receptor antagonist, did not inhibit the action of ET-1. The transfected receptor stimulates phosphoinositide (PI) hydrolysis via a pertussis-sensitive pathway. Pretreatment of the membrane from 1C7 cells with dithio-bis-nitrobenzoic acid (DTNB) a negatively charged, nonpenetrating agent capable of oxidizing sulfhydryl groups, and N-ethyl-maleimide (NEM), a penetrating agent that causes irreversible alkylation of sulfhydryl groups, significantly reduces Bmax but has no effect on Kd. In whole cells, DTNB pretreatment abolishes the ability of ET-1 to stimulate PI hydrolysis.

Avian Sarcoma Viruses↗
PubMed1993

Effect of dietary carbohydrate and phenotype on sucrase, maltase, lactase, and alkaline phosphatase specific activity in SHR/N-cp rat.

The obese spontaneous hypertensive rat/NIH-corpulent (SHR/N-cp) rat exhibits some of the metabolic and pathologic alterations associated with non-insulin-dependent diabetes mellitus and hypertension. The current study was conducted to investigate the influence of phenotype (ob versus In) and source of dietary carbohydrate (sucrose versus starch) on intestinal sucrase, maltase, lactase, and alkaline phosphatase activity in SHR/N-cp rats. For 3 months, lean and obese male SHR/N-cp rats were fed isocaloric diets containing as the sole source of carbohydrate either 54% cooked corn starch or sucrose. Serum and urine markers for diabetes were observed in obese rats. Wet weight and length of intestines were significantly increased in obese rats compared with lean littermates. Among the intestinal enzymes measured, statistical tests confirmed that sucrase activity was significantly increased (P < 0.01) by both phenotype (ob > In) and feeding a sucrose diet. Diet alone (sucrose > starch) significantly increased (P < 0.05) maltase activity in obese rats, but had no effect on lean rats. Lactase activity was significantly higher (P < 0.05) in obese sucrose-fed rats compared with obese starch-fed and/or lean littermates. Statistical tests revealed that intestinal alkaline phosphatase activity was significantly altered (P < 0.05) by both phenotype and diet. Intestinal alkaline phosphatase was higher in starch-fed lean rats compared with lean littermates fed sucrose and to starch or sucrose-fed obese rats. These results are not indicative of a simple, nonspecific increase in intestinal enzyme activity, since the effects observed in intestinal alkaline phosphatase contrast the effects observed in intestinal sucrase, maltase, and lactase activity. These results indicate that both phenotype and diet alter structural and enzymatic intestinal activities of SHR/N-cp rats. Distinct variations in the observed intestinal enzymatic activities suggest that these enzymes are under the control of genetic, hormonal, and dietary factors. Rationale for these differences are discussed.

Alkaline Phosphatase↗