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Biomedical subjects

J King

Publications and source records attributed to J King.

At least 307 records · Page 17Linked to original sources

Total protection from hypoxic liver damage by fructose.

The purpose of these experiments was to evaluate the effect of carbohydrates on hypoxic cell death in the perfused rat liver. Lactate dehydrogenase (LDH) was released maximally at rates up to 300 U/g/h after 40 to 60 min of hypoxia in control livers from fasted rats or in livers perfused with glucose (20 mM). Fructose (20 mM) prevented the release of LDH completely. Rates of anaerobic glycolysis indexed by release of lactate were around 150 mumol/g/h in livers perfused with fructose but were undetectable in livers perfused with glucose. The results demonstrate that fructose prevents hypoxic damage in the liver presumably by providing glycolytic ATP in the absence of oxygen.

Anaerobiosis↗

Identification of the 9-aminoacridine/DNA complex responsible for photodynamic inactivation of P22.

Acridine dyes bound to the condensed DNA within phage particles sensitize them to inactivation by visible light. The mechanism involves absorption of photons by an acridine/DNA complex, generating singlet oxygen, which covalently damages nearby proteins needed for DNA injection [Bryant, J., & King, J. (1985) J. Mol. Biol. 180, 837-863]. Acridines and related dyes interact with double-stranded DNA through a number of binding modes. To determine in condensed phage DNA the binding mode responsible for this inactivation, we have studied the formation of the DNA/acridine target complexes for photoinactivation. Analysis of the kinetics of 9-aminoacridine binding to Salmonella phage P22 particles revealed the formation of two binding species, one of which appeared more rapidly and was apparently an intermediate in the formation of the second. The rapidly forming species represented DNA sites with intercalated acridines, while the more slowly forming species represented the subsequent binding of additional acridine molecules to the DNA backbone of sites already containing intercalated dye. The rates of photoinactivation correlated with the rate of binding of 9-aminoacridine to the DNA backbone. This suggests that the most effective species for sensitizing phage to light-induced damage has acridine molecules stacked alongside the backbone of a region with intercalated molecules.

Aminacrine↗

Rapid degradation of steroid sulfatase in multiple sulfatase deficiency.

Pulse labeling followed by SDS-PAGE electrophoresis of immunoprecipitated [35S]methionine-labeled steroid sulfatase (STS) gave a single band of molecular weight 65,000 daltons. After a chase period of 18 hours the material appeared as molecular weight approximately 64,000. No labeled STS could be detected in fibroblasts from individuals with STS deficient X-linked ichthyosis. Pulse-chase labeling of normal and multiple sulfatase deficiency (MSD) fibroblasts showed a normal rate of synthesis of STS in MSD during a 3 hour pulse but during the chase the STS of MSD cells disappeared with a half-life of 4 to 6 hours until approximately 25% of the material remained after 24 hr. STS of normal cells had a half-life of 6 days. The material produced in MSD cells had the same molecular size as normal and had the same amount of endoglycosidase sensitive carbohydrate as normal. The defect in MSD thus seems to result in degradation after the addition of N-linked oligosaccharides.

Acetylglucosaminidase↗

The nucleotide sequence of the Escherichia coli K12 dnaJ+ gene. A gene that encodes a heat shock protein.

The Escherichia coli dnaJ gene product is required for bacteriophage lambda DNA replication at all temperatures. It is also essential for bacterial viability in at least some conditions, since mutations in it result in temperature-sensitive bacterial growth. We have previously cloned the dnaJ gene and shown that its product migrates as a Mr 37,000 polypeptide under denaturing conditions. Here we present the primary DNA sequence of the dnaJ gene. It codes for a processed basic protein (63 basic and 51 acidic amino acids) composed of 375 amino acids totaling Mr 40,973. The predicted NH2-terminal amino acid sequence, overall amino acid composition, and isoelectric point agree well with those of the purified protein. We present evidence that the rate of expression of the dnaJ protein is increased by heat shock under the control of the htpR (rpoH) gene product.

Amino Acid Sequence↗

Kunjin virus encephalomyelitis.

Kunjin virus encephalomyelitis is described in a 49-year-old man who presented with an episode of acute encephalitis. He developed profound bulbar, truncal and proximal muscle weakness suggestive of damage to cranial motor nuclei and anterior horn cells. This resolved very slowly. A marked rise in antibody titres to Kunjin virus was shown by haemagglutination inhibition tests. Specific IgM antibodies were detected only against Kunjin virus.

Antibodies, Viral↗

What happens to wild animals with broken bones?

Orthopaedic teaching suggests that long-bone fractures in wild animals are not uncommon and that they can heal naturally. This paper investigates this statement. The unsystematic collection of specimens for museums has perpetuated the idea that these fractures are not uncommon. Many fractures in adult skeletons seem to have occurred while the animal was still young. A review of the original skeletons in two museums does not support the view that major long-bone fractures in adult wild animals heal well. Contemporary observations on primates in the wild over long periods show that fractures of long bones in adult wild primates are rare and usually fatal, while falls which might be associated with juvenile fractures are much more common and may well be the source of the many well-healed fractures found in museum collections.

Age Factors↗

Blood flow in the ascending and descending aorta in term newborn infants.

The combination of 2-dimensional real-time and pulsed Doppler echocardiography provides a noninvasive method of measuring blood flow and has been used to study blood flow at the lower thoracic level in the descending aorta of the human fetus. Using these techniques, we evaluated the proportion of cardiac output distributed through the descending aorta in 20 healthy term newborn infants at 1-6 days of age. Blood flow in the ascending aorta was 759 +/- 135 ml/min (mean +/- S.D.) and in the descending aorta 482 +/- 92 ml/min indicating that 63.8% of the left ventricular output is distributed through the descending aorta. Peak systolic and mean blood flow velocities were comparable at the two sites, whereas the diameter of the descending aorta was 19% smaller than that of the ascending aorta. The changes in aortic blood flow were correlated with the changes in aortic diameter.

Aorta↗

Imipramine in adolescent major depression: plasma level and clinical response.

Thirty-four adolescents with mean age 14.25 years who met RDC criteria for major depressive disorder as assessed with the K-SADS, were treated for 6 weeks on a fixed schedule of imipramine hydrochloride titrated to a dosage of 5.0 mg/kg/day except as limited by side effects. Mean dose was 246 mg/day (4.5 mg/kg/day). In spite of good indications of compliance with treatment only 44% of the adolescents improved to the level of no or only slight depressed mood or anhedonia, though most had less depressive symptomatology at the end of treatment. There was neither a linear nor curvilinear relationship between total plasma level of IMI plus DMI and clinical response, despite a wide range of both plasma level (77 ng/ml to 986 ng/ml) and outcome. Adolescents with associated separation anxiety had significantly poorer response to treatment of their depressive disorder than those with major depression alone. Poor response was also weakly associated with being female, having endogenous subtype of depression, and having higher plasma IMI (but not DMI) level. In the context of similar studies of IMI on depression in other age groups, it is hypothesized that high levels of sex hormones during adolescence and young adulthood may interfere with IMI's antidepressant effects. It is concluded that other types of antidepressants should be tested in adolescents with major depression.

Adolescent↗

Echocardiographic measurements in normal preterm and term neonates.

To the purpose of better defining normative data on intracardiac dimensions and systolic time intervals in very low birth weight infants, we collected M-mode echocardiograms from 210 healthy preterm and term neonates with birth weights between 780 and 5,350 g and gestational ages ranging from 26 to 43 weeks. Fifty-nine neonates were less than 24 h, 62 were 25-48 h, and 89 were 48-144 h of age. Diastolic and systolic left ventricular dimensions increased gradually with advancing birth weight (r = +0.84 and 0.78). Left atrial and aortic root dimensions tended to show a parabolic relationship with birth weight, increments were reduced at higher birth weights (r = +0.92 and 0.85). The shortening fraction of the left ventricle (mean +/- SD 33.8 +/- 4.9%) and the left atrial/aortic ratio (1.16 +/- 0.10) were constant throughout all weight subgroups. Pre-ejection periods and ejection times of both ventricles were reduced in preterm infants due to their higher heart rates, but left and right ventricular PEP/ET ratios in preterm and term infants were comparable. Septal thickness in diastole and in systole tended to increase slowly with advancing birth weight, but correlation coefficients were low. This information is currently used as data base for a computer program to interpret M-mode echocardiograms performed in our nursery.

Birth Weight↗

Normal values of aortic root measurements in neonates.

Aortic root diameter measurements were obtained during the first week of life by M-mode echocardiography using leading edge methodology during early diastole in 172 preterm and 228 term neonates. At least 40 newborns were included in each 500-g birth-weight subgroup from 750 to 4750 g. The aortic root diameter increased linearly from 0.63 +/- 0.04 cm in newborns with birth weights of 750-1249 g to 1.06 +/- 0.06 cm in newborns of 4250-4750 g.

Aorta↗

A late gene product of phage P22 affecting virus infectivity.

Gene 14 is a recently discovered late gene of phage P22, mapping between the DNA injection and head completion genes (P. Youderian and M. Susskind (1980), Virology 107, 258-269). The gene 14 product has not been detected in phage particles. We have studied the defective phenotype of amber mutants in gene 14 to determine the role of gp14. The yield of physical particles from 14- infections is normal, but the infectivity of those particles is reduced by 60-80%. The noninfectious particles adsorb to but do not kill the host cell, as if they were defective in DNA injection. No differences in morphology, DNA composition, DNA permutation, or protein composition have been detected between 14- and wild-type particles. Procapsids, the capsid precursor to DNA packaging, exhibit a similar reduction in viability when isolated from 14- infected cells, assayed by in vitro DNA packaging. This is consistent with the gene 14 product functioning in the assembly or maturation of the procapsid. The three DNA injection proteins, encoded by genes 7, 16, and 20, are assembled into the particle at the procapsid stage. The defect in 14- particles may arise from improper organization or modification of one or more of the three proteins needed for DNA injection.

Crosses, Genetic↗

Cardiac output in infants of insulin-dependent diabetic mothers.

The purpose of our study was to quantitate left ventricular outflow obstruction in the infant of the diabetic mother (IDM) through estimation of cardiac output by pulsed Doppler ultrasound. We evaluated 42 IDMs (White class B, C, or D) and compared them with two control groups, one similar in birth weight and the other similar in gestational age. Ventricular septal hypertrophy was found in 18 (43%) of 42 of the IDMs, but in none of the control infants. Morbidity increased with advancing septal thickness. None had hyaline membrane disease. Twenty-nine IDMs were asymptomatic, 11 of whom had septal hypertrophy. Thirteen IDMs developed congestive heart failure, seven of whom had septal hypertrophy. Cardiac output per kilogram diminished linearly with increasing septal thickness (r = -0.78, P less than 0.001) secondary to reduced stroke volumes at comparable heart rates. The IDMs had higher left atrial/aortic ratios and greater right ventricular systolic time intervals than the control infants. We conclude that cardiac output is significantly reduced in IDMs with septal hypertrophy. This reduction is secondary to reduced stroke volume and is directly related to the degree of septal hypertrophy.

Birth Weight↗

Guinea pig striatum as a model of human dopamine deamination: the role of monoamine oxidase isozyme ratio, localization, and affinity for substrate in synaptic dopamine metabolism.

The kinetic properties of type A and type B monoamine oxidase (MAO) were examined in guinea pig striatum, rat striatum, and autopsied human caudate nucleus using 3,4-dihydroxyphenylethylamine (dopamine, DA) as the substrate. MAO isozyme ratio in guinea pig striatum (28% type A/72% type B) was similar to that in human caudate nucleus (25% type A/75% type B) but different from that in rat striatum (76% type A/24% type B). Additional similarities between guinea pig striatum and human caudate nucleus were demonstrated for the affinity constants (Km) of each MAO) isozyme toward DA. Endogenous concentrations of DA, 3-methoxytyramine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were also measured in guinea pig and rat striatum following selective type A (clorgyline-treated) and type B (deprenyl-treated) MAO inhibition. In guinea pig, DA metabolism was equally but only partially affected by clorgyline or deprenyl alone. Combined treatment with clorgyline and deprenyl was required for maximal alterations in DA metabolism. By contrast, DA metabolism in rat striatum was extensively altered by clorgyline but unaffected by deprenyl alone. Finally, the deamination of DA in synaptosomes from guinea pig striatum was examined following selective MAO isozyme inhibition. Neither clorgyline nor deprenyl alone reduced synaptosomal DA deamination. However, clorgyline and deprenyl together reduced DA deamination by 94%. These results suggest that the isozyme localization and/or isozyme affinity for DA, rather than the absolute isozyme content, determines the relative importance of type A and type B MAO in synaptic DA deamination. Moreover, based on the enzyme kinetic properties of each MAO isozyme, guinea pig striatum may serve as a suitable model of human DA deamination.

Animals↗