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Biomedical subjects

J L Johnston

Publications and source records attributed to J L Johnston.

At least 19 recordsLinked to original sources

Paresis of contralateral smooth pursuit and normal vestibular smooth eye movements after unilateral brainstem lesions.

Pursuit and vestibular smooth eye movements were measured in patients with lesions of the caudal brainstem tegmentum identified by magnetic resonance imaging (MRI) and computed tomography (CT), with neuropathological correlation in 1 patient. Contralateral smooth pursuit gain was significantly lower than ipsilateral gain in each patient. Ipsilateral smooth pursuit gain was also subnormal in patients with unilateral pontine damage that caused slowing of ipsilateral saccades. Horizontal vestibulo-ocular reflex gain and phase were normal. These quantitative correlations indicate that lesions of the pontine tegmentum that paralyze ipsilateral saccades can spare the vestibulo-ocular reflex, and that smooth pursuit movement and the vestibulo-ocular reflex can be impaired independently by pontine or medullary lesions. In contrast to lesions at other sites, unilateral lesions of the pontine or medullary tegmentum impair contralateral smooth pursuit more than ipsilateral pursuit movements. These findings provide evidence that a double decussating pathway mediates smooth pursuit; the first decussation is from the pons to the cerebellum, and the second decussation is from the vestibular nucleus to the contralateral abducens nucleus.

Brain Diseases

Spasm of fixation: a quantitative study.

Spasm of fixation, consisting of impaired initiation of saccades in the presence of fixation target, but normal initiation in the absence of a fixation target, was measured in a patient with cerebral hemispheric damage. When a central target was constantly present, the patient made horizontal saccades to the sudden appearance of a second target at very prolonged latencies (mean 369 ms). In the absence of a central fixation target, saccadic latency decreased to normal (197 ms). Extinction of a target for a gap interval elicited very short latency movements (122 ms), termed express saccades. The intervals between self-paced horizontal refixation saccades with the head immobile were prolonged, whereas voluntary refixation saccades with the head free to move occurred at shorter intervals. We postulate that cerebral hemispheric damage may cause spasm of visual fixation by disinhibiting the substantia nigra pars reticulata, thereby inhibiting the superior colliculus.

Adult

Third World aid.

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Developing Countries

Effects of energy restriction on norepinephrine turnover and serum glucose and fatty acids in lean mice.

Norepinephrine (NE) turnover rate was determined in several tissues of 5-week-old female mice fed a high carbohydrate diet (58% of energy as carbohydrate, 30% fat) either ad lib or restricted to 34 or 24 kJ/day (36 to 50% restriction) presented as 1 or 2 daily meals. When the restricted intakes were divided into 2 equal meals, daily NE turnover did not differ from that of ad lib-fed mice. When the above restricted amounts were provided as a single daily meal at the beginning of the dark period, NE turnover was 38% and 46% lower, respectively, in the heart only compared to ad lib-fed controls. Serum glucose and total free fatty acids were affected by dietary conditions known to produce sympathetic activation (high carbohydrate and high fat diets) and suppression (high protein diet and energy restriction as a single meal), but the changes were unrelated to fractional NE turnover. Thus, the lower NE turnover seen when food intake is restricted is due to the prolonged overnight fast and not due to the lower energy intake per se, and is not associated with serum concentration of glucose or total free fatty acids.

Animals

Psoriatic arthritis and myopathy.

We describe a patient with psoriatic arthritis and a myopathy. The myopathy did not follow the time course of topical steroid treatment, nor did the patient display any features of hypercorticolism or local steroid excess. No evidence was found to support the diagnosis of polymyositis. Psoriatic myopathy is an uncommonly described condition. Steroid induced myopathy shares some nonspecific features with psoriatic myopathy, but can be differentiated by the clinical response to cessation of steroid therapy. Myalgia and 24 h urine creatine elevation are 2 features not previously described in association with psoriatic myopathy. The latter appears to correlate with muscle weakness and may be useful in following the course of this disease.

Administration, Topical

Hypothalamic norepinephrine synthesis rate in overfed, underfed and fasted mice.

Hypothalamic norepinephrine (NE) synthesis rate during acute (1-day and 3-day) and chronic (11-day) overfeeding (14 kcal/day) and underfeeding (7 kcal/day) and 24 hr food deprivation was determined in four-week-old female mice. Mice were fed ad lib quantity or 51% of ad lib in a meal-feeding paradigm, a 60% fat diet providing constant protein intake across groups. NE synthesis rate, during the thermic effect of a meal, was calculated from the rate of NE accumulation after monoamine oxidase inhibition by pargyline and clorgyline. Acute and chronic underfeeding versus overfeeding had no effect on NE synthesis rate in the hypothalamus or in the rest of brain, or chronically in hypothalamic nuclei. In mice deprived of food for 24 hr, NE synthesis rate in the paraventricular nucleus only was five-fold higher than in fed mice. Thus, NE synthesis rate within the hypothalamus appears to be more related to short-term food intake regulation than to the thermic effect of eating or body fat content.

Animals

Antimicrobial resistance in nosocomial isolates of Staphylococcus haemolyticus.

Staphylococcus haemolyticus is frequently cultured from hospitalized patients and is characterized by resistance to multiple antimicrobial agents. We found that S. haemolyticus represented 70 of 524 (13%) coagulase-negative staphylococcal isolates identified by the clinical microbiology laboratories of two hospitals over 2 months. S. haemolyticus isolates were recovered from wounds (44%), urine (26%), blood (10%), and other sources (20%). All S. haemolyticus isolates were tested for susceptibility to six antimicrobial agents; 77% were resistant to three or more agents, and 41% were resistant to five or six agents. In addition, among 47 multiply resistant isolates, high MICs (greater than or equal to 6.25 micrograms/ml) of vancomycin (62% of isolates) and teicoplanin (91% of isolates) were found. DNA probes which were derived from S. epidermidis or S. aureus and which contained sequences associated with resistance to antimicrobial agents were used to detect specific genes in the total cellular and plasmid DNAs of 10 resistant S. haemolyticus isolates. Resistance gene probes and the numbers of resistant isolates hybridizing were as follows: methicillin, 10 of 10; gentamicin, 9 of 10; erythromycin, 7 of 10; and trimethoprim, 0 of 10. Genes for resistance to methicillin were found only in chromosomal locations, genes for resistance to gentamicin were found in both chromosomal and plasmid locations, and genes for resistance to erythromycin were found in plasmid locations only. With the exception of trimethoprim resistance determinants, similar genes were found among concurrently isolated multiply resistant S. epidermidis isolates from our hospitals. S. haemolyticus is a potentially important nosocomial species which readily acquires antimicrobial resistance genes and which shares, to some extent, in a common gene pool with S. epidermidis.

Anti-Bacterial Agents

Internuclear ophthalmoplegia in giant cell arteritis.

Ophthalmoplegia from ischemia to peripheral ocular motor nerves or muscles may complicate the course of giant cell arteritis (GCA). Although brainstem ischemia is known to occur in GCA, internuclear ophthalmoplegia has not been described. Two cases of biopsy-proven GCA are described in which internuclear ophthalmoplegia resulted from brainstem ischemia. Embolization from thrombosed extradural segments of inflammed vertebral arteries, or arteritis of brainstem perforating vessels may account for brainstem infarction. Rapid tapering of steroids was temporally related to brainstem infarction in both cases.

Aged

Short-term changes in energy intake and serum insulin, neutral amino acids, and urinary catecholamine excretion in women.

The effect of short-term undereating (4.2 MJ [1000 kcal] for 4 d) followed by overeating (12.6 MJ [3000 kcal] for 2 d) on fasting and 2-h postprandial serum glucose, insulin, and neutral amino acids and on urinary free and total norepinephrine and dopamine excretion was studied in 12 normal women. Protein and sodium intake was constant throughout the study. Serum glucose concentration was not affected by diet but the serum total neutral amino acids (ie, sum of valine, leucine, isoleucine, and phenylalanine) tended to increase during undereating and decrease during overeating. Serum tryptophan concentration, relative to the remaining neutral amino acids, was consequently lower during undereating than overeating. The postprandial increase in serum insulin level was greater during overeating than undereating. Urinary free norepinephrine and total dopamine levels were also increased during overeating, suggesting both sympathetic and dopaminergic activation during overeating after undereating.

Adult

Body fat assessed from body density and estimated from skinfold thickness in normal children and children with cystic fibrosis.

Body density and skinfold thickness at four sites were measured in 140 normal boys, 168 normal girls, and 6 boys and 7 girls with cystic fibrosis, all aged 8-14 y. Prediction equations for the normal boys and girls for the estimation of body-fat content from skinfold measurements were derived from linear regression of body density vs the log of the sum of the skinfold thickness. The relationship between body density and the log of the sum of the skinfold measurements differed from normal for the boys and girls with cystic fibrosis because of their high body density even though their large residual volume was corrected for. However the sum of skinfold measurements in the children with cystic fibrosis did not differ from normal. Thus body fat percent of these children with cystic fibrosis was underestimated when calculated from body density and invalid when calculated from skinfold thickness.

Adipose Tissue

In-vitro activity of LY146032 against Staphylococcus aureus and S. epidermidis.

The antibacterial activity of LY146032, a new cyclic polypeptide, was compared with that of vancomycin against 163 isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus and S. epidermidis. The MICs of LY146032 and vancomycin for 90% of the isolates were 1.0 mg/l and 2.0-4.0 mg/l, respectively. Interpretative guidelines for 15 micrograms and 30 micrograms LY146032 discs could not be established because all isolates tested were susceptible to LY146032, on the basis of achievable serum levels. With one exception, MBC to MIC ratios of LY146032 and vancomycin were less than or equal to 2. Inoculum size had minimal effect on ratios. In time-kill studies, both drugs were 99.9% bactericidal at 6 h for four isolates at concentrations four times the MBC or less. No change in LY146032 activity was observed between isogenic pairs that were resistant to other antibiotics. Thus, LY146032 was very active in vitro against all staphylococcal isolates.

Anti-Bacterial Agents

Effects of dietary protein, energy and tyrosine on central and peripheral norepinephrine turnover in mice.

Norepinephrine (NE) turnover rate and tyrosine concentrations were assessed in several tissues of 5-wk-old female lean mice that were fed diets of 20% protein (1.2% tyrosine), 40% protein (2.4% tyrosine) or tyrosine-supplemented diets of 40% protein with 4 or 8% tyrosine or 20% protein with 4% tyrosine for 4 d. Mice fed the 40% protein diet had significantly lower NE turnover rates in interscapular brown adipose tissue, heart and kidney (66, 64 and 49%, respectively) and nonsignificantly lower (84%) turnover rate in brain than did mice fed the 20% protein diet, but plasma and tissue tyrosine concentrations did not differ. When energy intake of the 20% protein-fed mice was restricted to 92% of the 40% protein-fed mice, tyrosine concentration in plasma and tissues was lower by half, but NE turnover rate did not differ between the two groups. Supplementation of the 40 or 20% diets with tyrosine, resulting in twofold higher plasma and tissue tyrosine concentrations, had no effect on NE turnover rate in any organ examined. We conclude that both energy intake and dietary protein concentration affect sympathetic nervous system activity in young mice. Tyrosine does not mediate or alter these changes.

Adipose Tissue

Molecular epidemiology of trimethoprim resistance among coagulase-negative staphylococci.

A 42% (70 of 167 isolates) incidence of resistance to 20 micrograms of trimethoprim per ml was found among clinical isolates of coagulase-negative staphylococci from two hospitals. A specific trimethoprim resistance gene probe from a conjugative Staphylococcus aereus plasmid was used to investigate the location of the trimethoprim resistance gene among 29 isolates. In 14 trimethoprim-resistant isolates, the probe hybridized with only chromosomal DNA, in 9 it hybridized with only plasmid DNA, and in 1 isolate both plasmid and chromosomal sequences showed hybridization. In five isolates there was no hybridization of the probe with either chromosomal or plasmid DNA. Four of these five nonhybridizing isolates were Staphylococcus haemolyticus. In contrast, all 22 Staphylococcus epidermidis isolates tested hybridized with the probe. The presence of the trimethoprim resistance gene in a chromosomal location was correlated with a lower MIC (median, 80 micrograms/ml) than when it was plasmid encoded (median, 1,250 micrograms/ml). Restriction endonuclease mapping as well as DNA hybridization of cloned plasmid and chromosomal DNA showed that there were 2.7 kilobases of common DNA in the two loci. This included the 500 base pairs of DNA mediating trimethoprim resistance and a total of 2.2 kilobases of 3'- and 5'-flanking sequences. The presence of the same gene and flanking sequences in chromosomal and plasmid locations suggests that the trimethoprim resistance determinant is translocated among different genetic loci.

Chromosome Mapping