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Biomedical subjects

M Richardson

Publications and source records attributed to M Richardson.

At least 163 records · Page 9Linked to original sources

Proteoglycan alterations in the aortic intima-media of alloxan-diabetic rabbits: an ultrastructural and biochemical study.

Proteoglycans and glycosaminoglycans in the aortic intima of diabetic rabbits and age-matched controls were examined at 2 weeks and 3, 6, and 12 months after alloxan (or saline) treatment. Measurements were made by morphometric analysis of ruthenium red-stained large proteoglycan granules (LPG) in electron micrographs and by analysis of 35S-labeled glycosaminoglycans, extracted and purified from the intima-media of aortas of rabbits which had been injected with 35S-sulfate 18 hr before exsanguination. There was a progressive increase in the area of the aortic intima with time which was greater in diabetic than in control rabbits. The concentration of proteoglycan (LPG/microns 2) and the concentration of the 35S-glycosaminoglycans in diabetic intima-media were similar to respective values of control intima-media throughout the 12 months. However, the specific radioactivity of the [35S]glycosaminoglycan pool from intima-media of diabetic rabbits was significantly less than that from controls (P < 0.001) at 6 and 12 months. In addition, the staining intensity of LPG of the diabetic compared to control extracellular matrix was decreased at these times. The profile and electrophoretic mobility of the glycosaminoglycan types were similar in diabetic and control intima-media. We conclude that the onset of diabetes in the rabbit has altered the metabolic turnover but not the concentration, sulfate content or profile of aortic intima-media proteoglycan and glycosaminoglycans.

Alloxan↗

Refinement of the X-linked cleft palate and ankyloglossia (CPX) localisation by genetic mapping in an Icelandic kindred.

The gene responsible for X-linked cleft palate and ankyloglossia (CPX) has previously been localized to the proximal region of the q arm of the X chromosome in both Icelandic and North American Indian kindreds. In this study, further linkage analysis has been performed on the Icelandic family and has resulted in a significant reduction in the size of the interval containing the mutated gene. A new polymorphism at DXS95, together with DXS1002 and DXS349, defines the proximal boundary of the CPX interval, whereas DXYS1X defines the distal boundary. Multipoint analysis supports this localisation with a peak lod score of 12.7, more than 2 lod score units higher than the next most likely position. In order to assess the physical size of the CPX interval prior to initiating yeast artificial chromosome cloning, metaphase fluorescence in situ hybridisation analysis was performed with the closest flanking markers. The size of the interval between DXS95 and DXYS1X was estimated to be approximately 2-3 Mb.

Chromosome Mapping↗

Purification and amino acid sequence of the insecticidal neurotoxin Tx4(6-1) from the venom of the 'armed' spider Phoneutria nigriventer (Keys).

An insecticidal peptide referred to as Tx4(6-1) was purified from the venom of the spider Phoneutria nigriventer by a combination of gel filtration, reverse-phase fast liquid chromatography on Pep-RPC, reverse-phase high performance liquid chromatography (HPLC) on Vydac C18 and ion-exchange HPLC on cationic columns. Tx4(6-1) is highly toxic to house flies. At levels of 0.5 ng/house fly it caused excitatory symptoms immediately after intrathoracical injection. However, in mice injections of 0.03 mg of the toxin intracerebroventricularly resulted in no apparent symptoms of intoxication. These results demonstrate that Tx4(6-1) of P. nigriventer has no toxicity for mice, and suggest that it is a specific anti-insect toxin. The mol. wt (5244.6) and purity of the toxin were determined by desorption mass spectroscopy. The complete amino acid sequence of this toxin was established by direct automated Edman degradation and manual 4-N,N'-dimethylaminoazobenzene-4'isothiocyanate/phenyl-isothiocyanate microsequence analyses of peptides obtained from digests with various proteases. The protein contains 48 amino acids including 10 Cys and 6 Lys. The N-terminal and C-terminal residues were Cys. The Tx4(6-1) sequence differs from that of previously characterized neurotoxins found in the same and other venom spiders, but exhibited sequence similarities in the location of the Cys residues.

Amino Acid Sequence↗

Intravenous propofol vs thiamylal-isoflurane for caesarean section, comparative maternal and neonatal effects.

Several studies on propofol (Diprivan) for induction of anaesthesia during caesarean section have demonstrated its safety, however, it safety during maintenance of anaesthesia is not yet fully evaluated. The present study was undertaken to compare the maternal and neonatal effects of propofol or isoflurane in 74 term parturients undergoing primary or repeat caesarean section. Patients were randomly assigned to two groups, propofol group (n = 37) received propofol 1.5-2.5 mg.kg-1 for induction followed by a continuous infusion of propofol of 0.05-0.2 mg.kg-1.min-1. The isoflurane group (n = 37) received thiamylal 3-4mg.kg-1 for induction followed by isoflurane 0.25-0.75% for maintenance. All patients had rapid sequence induction using succinylcholine and endotracheal intubation, 50% N2O and O2 were used in all patients until delivery. After delivery N2O concentration was increased to 67% and intravenous butorphanol (Stadol) was given as needed. Patients in the propofol group had less hypertension after intubation (P < 0.05) and this was also of shorter duration compared to patients in the isoflurane group (5 min vs 10 min respectively). Maternal blood loss as well as intraoperative awareness and recovery time did not differ significantly between the two groups. Neonatal status as ascertained by Apgar scores, cord acid base status and the neurological and adaptive capacity scores (NACS) was equally good in both groups. It is concluded that propofol used for induction and maintenance of anaesthesia is a safe alternative to thiamylal/isoflurane for patients undergoing caesarean section and is associated with less hypertensive response during laryngoscopy and intubation.

Acid-Base Equilibrium↗

Desflurane: a new volatile anesthetic for cesarean section. Maternal and neonatal effects.

Desflurane, a new volatile anesthetic agent with low blood/gas solubility, has recently been studied in clinical and animal trials but its use in obstetrics has not been adequately evaluated. This prospective study was undertaken to evaluate the maternal and neonatal effects of desflurane in obstetrical patients. Seventy-five healthy parturients undergoing primary or repeat cesarean section were randomly assigned to one of three groups of 25 each, end-tidal 3% desflurane, 6% desflurane or 0.6% enflurane, combined with 50% N2O and O2. All patients had rapid sequence induction of anesthesia with thiopentone sodium followed by succinylcholine for tracheal intubation. After delivery, anesthesia was maintained with reduced concentration of desflurane or enflurane with 67% N2O in O2, supplemented by butorphanol tartrate. Maternal hemodynamic parameters, blood loss and maternal awareness during surgery were monitored. Neonatal outcome was evaluated by Apgar scores, neurological and adaptive capacity scores (NACS), cord blood gas and acid-base status, and time to sustained respiration (TSR). Maternal blood loss did not differ significantly between the three groups and none of the patients developed intraoperative awareness. All three groups responded to psychomotor performance equally fast. Patients in all three groups developed transient hypertension and tachycardia during induction of anesthesia which returned to baseline values in approximately 5 min. Neonatal outcome was equally good in the three groups. More neonates in the 6% desflurane group had TSR > 90 s compared to the 3% desflurane group (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Obstetrical↗

A review of intestinal injury from blunt abdominal trauma.

Eighty-five patients who suffered blunt trauma to the small intestine and/or to the colon were treated at either the Royal Brisbane Hospital (RBH), Brisbane, Queensland or the Flinders Medical Centre (FMC), Adelaide, South Australia, between 1980 and 1991. Data were collected by retrospective review of case notes from the medical records departments of both hospitals and analysed with respect to the cause, the anatomical distribution, the diagnostic methods and the mortality of these injuries. There were 129 intestinal injuries (44 colonic and 85 small bowel). Five (5.9%) deaths were recorded. Seventy-two patients (84.7%) were injured in vehicular accidents. Fifty-three patients (62.4%) underwent laparotomy based on clinical findings alone. Diagnostic peritoneal lavage (DPL) was used in 24 cases and was positive in 22 (91.7%). The most common small bowel injury was ¿blowout' perforation on the antimesenteric border of the bowel (55.5%). The most common colonic injury was a serosal tear/bruise (62.2%).

Abdominal Injuries↗

Injuries to the ulnar carpometacarpal region: are they being underdiagnosed?

Thirteen cases with radiographic evidence of injury to the ulnar side of the hand are reviewed. These injuries included intraarticular fractures and/or dislocations of the fourth and fifth carpometacarpal joints and associated bones collectively discussed here as the ulnar carpometacarpal region. In nine the extent of the injury was not appreciated on first presentation. Injuries to this region are often difficult to assess clinically and radiographically even in experienced hands. In our experience computerized tomography (CT) scans in the longitudinal and longitudinal oblique axis best display the ulnar carpometacarpal joint surfaces and their relationship to each other. We recommend CT of the ulnar carpometacarpal region where clinical evidence of an injury to this region is not in keeping with the plain radiographic findings, and when planning surgery on a complex injury in this region.

Adolescent↗

Infection control and human immunodeficiency virus: perceptions of risk among nurses and hospital domestic workers.

In December 1993 the first case of patient-to-patient transmission of human immunodeficiency virus (HIV), at a doctor's surgery in New South Wales, was documented. In an environment of heightened anxiety about HIV transmission and the adequacy of infection-control measures taken by health providers, it is important to explore perceptions of occupational risk of exposure to infection among hospital workers, reasons why hospital domestic workers sometimes depart from standard procedure in infection control, and how they regard the patients who have infectious diseases. In this study, at an infectious diseases hospital where there is an acute awareness of such issues, nurses had accurate knowledge about control of infection, including HIV, but had limited trust of that knowledge. They gave rationales for why they sometimes departed from infection-control procedures. They had low levels of fear of homosexuals and of acquired immune deficiency syndrome. The hospital domestic workers had lower levels of accurate knowledge about infection control, including HIV, and less trust of that knowledge and of protection by health provider from occupational exposure to infection. They had low levels of fear of homosexuals and HIV. Both groups sought regular, small-group, interactive education programs on infection control and HIV to allow them to discuss their concerns. Participatory education of workers should include eliciting concerns of participants, and should discuss concerns regarding administrators' and educators' interests in their safety and wellbeing.

Adult↗

Comparative metabolism of plasminogen glycoforms I and II in the alloxan-diabetic rabbit.

The metabolism of plasminogen glycoforms I and II was measured in alloxan-induced diabetic and in age-matched control rabbits. Radiolabeled plasminogen I and II were degraded significantly more slowly in diabetic compared with control rabbits; plasminogen II [half-time (T1/2), 1.31 days] was degraded faster than plasminogen I (T1/2), 1.86 days) in diabetic rabbits and in control rabbits (T1/2, 1.18 and 1.58 days, respectively). From the catabolic rates and relative quantities in plasma, we calculated that approximately four molecules of plasminogen II were degraded for one molecule of plasminogen I in the diabetic and control rabbits. To verify this later observation, plasminogen I and II production by diabetic rabbit livers was compared with that by the control livers in vitro. During perfusion with [3H]leucine, 3H-labeled protein was released more slowly from diabetic than from control livers, but no quantitative difference in total plasminogen yield between diabetic and control livers was found. Nevertheless, plasminogen II was produced 0.7 +/- 0.4 and 4.3 +/- 0.3 times faster than plasminogen I by diabetic and control livers, respectively. Plasminogen metabolism in the diabetic rabbit did not differ qualitatively from that in the control rabbit except that catabolism was slowed.

Animals↗

'CO2-ligated' cytochrome c oxidase: characterization and comparison with the Cl- -ligated enzyme.

A form of fully oxidized bovine heart cytochrome c oxidase that is induced by CO2/HCO3- is described. The ligand-binding properties of this form are similar to those of Cl(-)-ligated oxidase [Moody, Cooper and Rich (1991) Biochim. Biophys. Acta 1059, 189-207]. Both bind cyanide at a rate (0.2 M-1.s-1 at pH 6.5) intermediate between the rate of binding to the fast and slow forms of the enzyme, and binding of formate to both is almost undetectable. They are also similar in showing poor reactivity with H2O2, or with CO in the presence of O2, which, with fast oxidase, induce the formation of the 'ferryl' and 'peroxy' states respectively. However, there is a clear difference in the near-u.v./visible absorption spectra of the two forms; that induced by CO2/HCO3- has a Soret maximum at 427 nm whereas Cl(-)-ligated oxidase has a Soret maximum similar to that of fast oxidase at about 424 nm. It appears that both CO2/HCO3- and Cl- are members of a class of ligands that lowers the reactivity of the binuclear centre but does not impede intramolecular electron transfer from haem a to the binuclear centre, unlike the putative endogenous ligand responsible for slow oxidase.

Animals↗

A unique interhelical insertion in plasminogen activator inhibitor-2 contains three glutamines, Gln83, Gln84, Gln86, essential for transglutaminase-mediated cross-linking.

Plasminogen activator inhibitor type 2 (PAI-2) prevents fibrinolysis by blocking plasminogen activators. It is expressed principally by trophoblast cells and macrophages. PAI-2 in trophoblast membranes has been found cross-linked to large complexes apparently catalyzed by trophoblast transglutaminase (Jensen, P. H., Lorand, L., Ebbesen, P., and Gliemann, J. (1993) Eur. J. Biochem. 214, 141-146). Recombinant human PAI-2 was labeled with [14C]putrescine catalyzed by guinea pig liver transglutaminase. The [14C]putrescine-labeled PAI-2 was digested with cyanogen bromide and trypsin, and the peptides were purified by reverse-phase high performance chromatography. Amino acid sequencing and plasma desorption mass spectrometry of the labeled peptides revealed [14C]putrescine incorporation at Gln83, Gln84, and Gln86. These residues are present in a PAI-2-specific region of 33 amino acids that is inserted between helices C and D and which probably represents a unique solvent-exposed domain. A PAI-2 mutant lacking this insertion was determined not to be a substrate for transglutaminase by [14C]putrescine incorporation and could not form transglutaminase-catalyzed polymers. Thus, the unique PAI-2 insertion represents a functional domain that, by virtue of its transglutaminase acceptor sites, allows participation in binding reactions without affecting the inhibitory function of PAI-2.

Amino Acid Sequence↗

Pea (Pisum sativum L.) seed isolectins 1 and 2 and pea root lectin result from carboxypeptidase-like processing of a single gene product.

The complete amino acid sequences of the alpha-subunits of pea (Pisum sativum L.) seed and root lectin, the C-terminal amino acids of the beta-subunits of pea seed lectin, and most of the sequence of the beta-subunit of pea root lectin were determined. In contrast to earlier reports it was shown that the beta-subunits of both seed isolectins end at Asn-181. The alpha 1 subunits end at Gln-241 (major fraction) or Lys-240 (minor fraction), whereas the alpha 2 subunits end at Ser-239, Ser-238, Ser-237 or Thr-236. psl cDNA clones from seed are identical to psl cDNA clones from root, and root PSL is identical to seed PSL2, ending at Ser-239, Ser-238 or Ser-237. It seems that the presence of Lys-240 is the sole determinant of the charge difference between pea isolectins. PSL1 can be converted into PSL2 by carboxypeptidase P from Penicillium janthinellum. These results confirm that PSL from roots is encoded by the same gene as PSL from seeds. Thus, it seems that, next to an Asn-X specific protease responsible for the processing at positions 181/182 and 187/188, a carboxypeptidase is responsible for the conversion of PSL1 and PSL2, which is probably the final processing product.

Amino Acid Sequence↗

Homology between the seed cytolysin enterolobin and bacterial aerolysins.

Enterolobin, a 55-kDa cytolytic, inflammatory, and insecticidal protein isolated from seeds of the Brazilian tree Enterolobium contortisiliquum (Leguminosae-Mimosoideae) has been further purified and partially sequenced by using both manual and automated methods. A computational search of enterolobin partial amino acid sequence against the PIR database revealed possible sequence similarities with aerolysins, cytolytic proteins from Aeromonas species. An alignment of enterolobin partial sequence to the amino acid sequences of A. hydrophila and A. sobria aerolysins showed several similar regions with many residue identities. The seed protein enterolobin and the bacterial aerolysins may be homologous proteins despite the distant phylogenetic relationship.

Amino Acid Sequence↗

Early lesion development in the aortas of rabbits fed low-fat, cholesterol-free, semipurified casein diet.

The initial endothelial morphological alterations and the development of raised, lipid-containing lesions in rabbit aortas were examined after 1 and 3 months on a casein-enriched, semipurified, cholesterol-free diet. The alterations were compared with those in rabbits fed soy-protein in the place of casein and with age-matched, chow-fed, control animals. Using immunohistochemistry macrophages, T-lymphocytes, and smooth muscle cells were identified in the lesions, and an expression of leukocyte adhesion molecules, VCAM-1, ICAM-1 and, occasionally, E-selectin was seen in sections of the aortas of casein-fed rabbits. The initial alterations in the endothelium appear to include evidence of endothelial injury and white blood cell adhesion. No evidence of extracellular liposome formation was observed. This model of atherogenesis is consistent with endothelial injury being an important component of diet-induced atherogenesis and has similarities to human atherosclerosis.

Animals↗

A new technique for surgical correction of bronchial stenosis.

Bronchial stenosis in children presents an even more challenging reconstructive procedure than does tracheal stenosis because of the smaller luminal diameter of the bronchus. Multiple techniques have been used, with varying success. Pericardium is readily available and can be used as a bronchial patch; however, it is floppy and tends to collapse, resulting in luminal narrowing and eventual scarring leading to restenosis. We devised a technique that uses glutaraldehyde-soaked pericardium with a rib cartilage stent to reconstruct the bronchus in two children who had main-stem bronchial stenosis.

Bioprosthesis↗