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Biomedical subjects

J D Matthew

Publications and source records attributed to J D Matthew.

11 recordsLinked to original sources
PubMed2000

Contractile properties and proteins of smooth muscles of a calponin knockout mouse.

The role of h1-calponin in regulating the contractile properties of smooth muscle was investigated in bladder and vas deferens of mice carrying a targeted mutation in both alleles designed to inactivate the basic calponin gene. These calponin knockout (KO) mice displayed no detectable h1-calponin in their smooth muscles. The amplitudes of Ca2+ sensitization, force and Ca2+ sensitivity were not significantly different in permeabilized smooth muscle of KO compared with wild-type (WT) mice, nor were the delays in onset and half-times of Ca2+ sensitization, initiated by flash photolysis of caged GTPgammaS, different. The unloaded shortening velocity (Vus) of thiophosphorylated fibres was significantly (P<0.05) faster in the smooth muscle of KO than WT animals, but could be slowed by exogenous calponin to approximate WT levels; the concentration dependence of exogenous calponin slowing of Vus was proportional to its actomyosin binding in situ. Actin expression was reduced by 25-50%, relative to that of myosin heavy chain, in smooth muscle of KO mice, without any change in the relative distribution of the actin isoforms. We conclude that the faster Vus of smooth muscle of the KO mouse is consistent with, but does not prove without further study, physiological regulation of the crossbridge cycle by calponin. Our results show no detectable role of calponin in the signal transduction of the Ca2+-sensitization pathways in smooth muscle.

Animals↗
PubMed1998

Myosin essential light chain isoforms modulate the velocity of shortening propelled by nonphosphorylated cross-bridges.

The differential effects of essential light chain isoforms (LC17a and LC17b) on the mechanical properties of smooth muscle were determined by exchanging recombinant for endogenous LC17 in permeabilized smooth muscle treated with trifluoperazine (TFP). Co-precipitation with endogenous myosin heavy chain verified that 40-60% of endogenous LC17a could be exchanged for recombinant LC17a or LC17b. Upon addition of MgATP in Ca2+-free solution, recombinant LC17 exchange induced slow contractions unaccompanied by regulatory light chain (RLC) phosphorylation only in TFP-treated, but not in untreated, permeabilized smooth muscle; the shortening velocity and rate of force development were approximately 1.5 and 2 times faster, respectively, in response to LC17a than LC17b. Additional incubation with recombinant, thiophosphorylated RLC increased the shortening velocity, independent of the LC17 isoform exchanged. The LC17-induced contractions of TFP-treated muscles were abolished by prior addition of nonphosphorylated RLC. We suggest that LC17 stiffens the lever arm of myosin and, in the absence of regulation by RLC, permits cross-bridge cycling without requiring RLC phosphorylation. Our results are compatible with nonphosphorylated RLC acting as a repressor and with LC17 isoforms modulating the MgADP affinity and, consequently, rate of cooperative cycling of nonphosphorylated cross-bridges.

Adenosine Triphosphate↗
PubMed1998

Regulation of the cross-bridge cycle: the effects of MgADP, LC17 isoforms and telokin.

This review summarizes the role of MgADP in force maintenance by dephosphorylated cross-bridges in smooth muscle and a potential physiological role for telokin. In tonic, compared with phasic, smooth muscles the affinity of cross-bridges in approximately 5 times higher for MgADP and the apparent second-order rate constant for MgATP is approximately 3 times lower. This gives rise to a large population of dephosphorylated cross-bridges in tonic smooth muscle. Such cross-bridges are thought to be major determinants of the different relaxation kinetics of the two types of smooth muscle and contribute to force maintenance at low levels of MLC20 phosphorylation, termed 'catch-like state' (Somlyo & Somlyo 1967) or 'latch' (Dillon et al. 1981). The molecular basis of the different affinities for MgADP and MgATP between tonic and phasic smooth muscle myosin was explored by exchange of essential myosin light chain (LC17) isoforms. In phasic bladder smooth muscle the exchange of LC17b for LC17a caused a significant decrease in the unloaded shortening velocity of non-phosphorylated, slowly cycling cross-bridges, suggesting that the LC17 isoforms contribute to the nucleotide affinity of latch bridges. The role of telokin in Ca(2+)-desensitization in phasic smooth muscle is reviewed. Telokin, the independently expressed C-terminus of myosin light chain kinase, is extensively phosphorylated during forskolin- and 8-br-cGMP-induced relaxation in situ. Telokin accelerated dephosphorylation of the regulatory myosin light chain and relaxed rabbit ileum smooth muscle. The results suggest that telokin contributes to cAMP and/or cGMP kinase-mediated Ca(2+)-desensitization of phasic smooth muscles.

Adenosine Diphosphate↗
PubMed1997

The role of nitric oxide in inhibitory neurotransmission in the middle cerebral artery of the sheep.

1. The involvement of nitric oxide (NO) as a mediator of inhibitory neurotransmission and its potential release mechanism in sheep isolated middle cerebral artery rings was investigated using NO synthase inhibitors, haemolysate, superoxide dismutase (SOD) and omega-conotoxin GVIA. In the presence of guanethidine (5 microM) and atropine (2 microM), transmural nerve stimulation of precontracted artery rings elicited an endothelium-independent vasodilator response that could be abolished by tetrodotoxin. 2. The magnitude of the vasodilator response was virtually abolished by NG-nitro-L-arginine-p-nitroanilide (L-NAPNA; 100-500 microM) and significantly reduced by NG-nitro-L-arginine (50 microM) or haemolysate (1 microliter ml-1). NG-nitro-D-arginine (50 microM) had no effect. In the presence of the NO synthase inhibitors, addition of L-arginine (300 microM) produced either no effect or a partial, transient restoration of inhibitor responses following electrical field stimulation (EFS). L-NAPNA (100 microM) did not affect the relaxant response to the NO donor SIN-1. These results suggest that NO is involved in the relaxation elicited by transmural nerve stimulation. 3. Superoxide dismutase (SOD; 150 Uml-1) did not produce any significant changes in the magnitude of the EFS-induced vasodilation. Thus, superoxide anions appear not to be a limiting factor for NO-mediated neurogenic vasodilation in sheep MCA. 4. omega-Conotoxin GVIA (100 nM) caused an almost immediate abolition of the EFS-induced vasoconstrictor response at resting tension, but had no effect on the vasodilator response at all frequencies of stimulation (0.5-8 Hz) tested. Thus, the neurotransmission process mediating this vasodilator response does not appear to involve Ca2+ entry via N-type Ca2+ channels.

Anilides↗
PubMed1997

Inhibition of vasodilator neurotransmission in the sheep middle cerebral artery by VIP antiserum.

1. Middle cerebral artery rings from the sheep were relaxed by vasoactive intestinal peptide (VIP) (20-200 nM) or by stimulation of the vasodilator nerves, electrical field stimulation (EFS). 2. VIP antiserum 1:256 inhibited the relaxation produced by both exogenous VIP (from 70 +/- 5 to 32 +/- 9% of 5-HT-induced tone at 200 nM VIP) and by EFS (from 43 +/- 5 to 26 +/- 6% of 5-HT-induced tone after 20 min), while pre-immune serum was inactive. 3. Capsaicin (1 microM) produced a transient relaxation but did not alter the response to EFS which was subsequently inhibited by addition of L-NOArg (100 microM). VIP-induced relaxation was antagonized by L-NOArg (50 microM) (from 68 +/- 5 to 46 +/- 2% relaxation of 5-HT-induced tone) but not by D-NOArg. 4. Exogenous VIP produced an approximately 2.4-fold increase in cyclic GMP content which was prevented by preincubation with L-NOArg (100 microM) but not D-NOArg. 5. VIP and neuronal NOS immunoreactivity was co-localized to the same adventitial nerve fibres in the sheep middle cerebral artery. 6. These results provide evidence that neurogenic relaxation in the sheep middle cerebral artery is, at least in part, mediated by VIP, involving activation of NO synthase.

Animals↗
PubMed1993

Zinc supplementation in very-low-birth-weight infants.

Inadequate zinc intake may lead to poor growth and developmental outcome in very-low-birth-weight (VLBW; < 1,500 g) infants. Fifty-two infants (mean birth weight, 1,117 +/- 287 g; mean gestational age, 29 +/- 2.9 weeks) were randomly allocated to two groups. SUPP infants received a regular term formula plus zinc supplements (4.4 mg/L; final content, 11 mg/L); PLAC infants received the same formula plus placebo (final content, 6.7 mg/L). Infants started their formula at 1,853 +/- 109 g and consumed the formula for 6 months. All subjects were evaluated at 3, 6, 9, and 12 +/- 0.75 months corrected-for-gestational-age. At each evaluation, weight, length, and head circumference were measured, a Griffiths developmental assessment was performed, and a blood sample was taken. Higher plasma zinc levels (p < 0.05) were found in the SUPP group at 1 and 3 months, and improved linear growth velocity was found in the SUPP group over the study period for the whole group as well as for girls alone. Maximum motor development scores were higher (p = 0.018) in the SUPP (98 +/- 10) than the PLAC (90 +/- 8) group, indicating that increased zinc intake in early infancy may be beneficial to VLBW infants.

Double-Blind Method↗
PubMed1990

Iron status of very-low-birth-weight infants during the first 15 months of infancy.

The adequacy of iron stores in infants of very low birth weight (defined as less than 1500 g) in Canada is unknown. We monitored the iron status of 81 such infants at 3, 6, 9, 12 and 15 months of age. All of the infants were fed formula fortified with iron (13 mg/L) for at least 6 months, starting at 2 months of age. The plasma ferritin level decreased after the formula was no longer used. Although 90% of the infants were given cereal fortified with iron (30 mg of iron per 100 g) by 9 months of age, the plasma ferritin level continued to decrease. The level was less than 10 micrograms/L in 54% of the infants at 12 months of age and in 74% at 15 months; this indicated depleted iron stores. Because of delayed development very-low-birth-weight infants eat small amounts of cereal and therefore require iron-fortified formula throughout infancy.

Aging↗
PubMed1989

Trace elements in meconium from preterm and full-term infants.

Meconium samples from 23 preterm infants (birth weight = 1,097 +/- 359 g; gestational age 29 +/- 3 weeks, mean +/- SD) and 27 full-term infants (3,453 +/- 476 g; 39.5 +/- 1 weeks) were analyzed for zinc, copper, manganese, chromium and iron by atomic absorption spectrometry. Compared to meconium from preterm infants, full-term infants had an elevated (p less than 0.05) total excretion (microgram) of zinc (957 +/- 545 vs. 503 +/- 506), copper (245 +/- 256 vs. 128 +/- 94) and manganese (62 +/- 55 vs. 29 +/- 29), but not iron (190 +/- 147 vs. 332 +/- 532) or chromium (0.4 +/- 0.19 vs. 0.75 +/- 1.0). Two preterm infants had high losses (1.5 and 2 mg) of iron in their meconium. Zinc, copper and manganese losses into meconium appear to increase with gestation, whereas iron and chromium losses occur early in gestation and may be reabsorbed by term.

Chromium↗
PubMed1978

Neonatal transport: a controlled study of skilled assistance. Mortality and morbidity of neonates less than 1.5 kg birth weight.

To attempt to demonstrate the need for skilled care of sick neonates in transport, a modified randomized controlled study of infants being transported to this institution was carried out. Although special equipment was used, ambulances were not modified. Results of the first phase reported here show that infants weighing less than 1.5 kg at birth, transported by a trained physician and nurse, were significantly warmer, less hypotensive, and less acidotic on admission to the NICU. Mortality was significantly reduced, first week morbidity somewhat lessened, and duration of stay in hospital reduced by more than one third (P less than 0.01).

Ambulances↗
PubMedDate not supplied

Intravenous iron administration to very-low-birth-weight newborns receiving total and partial parenteral nutrition.

BACKGROUND: Intravenous iron supplements are not routinely administered to very-low-birth-weight newborns receiving total parenteral nutrition because of the possible increased risk of infection and because iron needs may be met with blood transfusions. METHODS: To assess the benefits of a prudent IV iron supplement (200 to 250 micrograms/kg/d), 26 very-low-birth-weight newborns (birth weight, 1005 +/- 302 g; gestational age, 28 +/- 2.3 weeks; mean +/- SD) were randomly allocated to receive total parenteral nutrition without iron (No-Iron) or with iron supplied as iron dextran (Iron). These newborns were followed at baseline (2 to 3 days after birth) and at weeks 1 to 4 thereafter. At each sampling time, urine samples, fecal samples (rarely), unused total parenteral nutrition solutions, blood products, and a blood sample (1 mL) were collected. RESULTS: There were no differences between the two groups in anthropometric measurements, hematologic or biochemical parameters, number or amount of blood transfusions (2.3 +/- 1.9), amount of blood removed for diagnostic purposes (44 +/- 16 mL), or number of septic events (n = 16). There was no difference between the groups for the total iron excreted; however, the Iron group retained more iron. Iron balance was negative for all but 10 newborns (No-Iron, 3; Iron, 7) throughout the study. CONCLUSIONS: A total iron intake of 400 micrograms/kg/d, half of which was provided by IV iron, is not sufficient to maintain iron balance or to meet fetal accretion rates (1000 micrograms/kg/d) in very-low-birth-weight newborns receiving total parenteral nutrition. Furthermore, endogenous iron from blood transfusions does not provide an adequate supply of iron.

Anthropometry↗