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Biomedical subjects

J Fleming

Publications and source records attributed to J Fleming.

At least 145 records · Page 8Linked to original sources

Effect of aminophylline on fatigue of the sternomastoid muscle in man.

The effect of intravenous aminophylline on the contractility of the sternomastoid muscle was measured in the fresh state and after the induction of significant fatigue in five normal subjects. Fatigue was produced by repetitive isometric neck flexion, for two seconds every four seconds at 70% of the maximum voluntary contractile force, continued until exhaustion. Each subject performed three experiments, one to two weeks apart, in random order. In experiment 1 fatiguing exercise and recovery were completed without aminophylline; in experiment 2 intravenous aminophylline was started 30 minutes before exercise and continued throughout the 60 minute recovery period; and in experiment 3 intravenous aminophylline was started immediately after the end of exercise. Aminophylline did not influence the frequency-force relationships, relaxation rate, or maximum voluntary contractile force in the fresh muscle. After fatiguing exercise there was a relatively selective reduction in force response to stimulation frequencies of less than 30 Hz, with little alteration in forces at higher frequencies--that is, low frequency fatigue--and this effect was present for the entire one hour study period. Aminophylline given before or immediately after fatigue did not influence the recovery of either low frequency fatigue or maximum voluntary contractile force. Aminophylline at therapeutic concentrations had no significant effect on the contractility or fatiguability of the normal human sternomastoid muscle.

Adult↗

Interaction between canine platelets and adult heartworms: platelet recognition of heartworm surfaces.

An interaction between blood platelets and adult heartworms was examined in vitro. Surfaces of glutaraldehyde-fixed heartworms, which were taken from infected dogs washed, and incubated in platelet-rich plasma (PRP), were evaluated by scanning electron microscopy. Adherence of platelets to heartworms occurred only with PRP from infected dogs. Aggregation to epinephrine and adenosine diphosphate of PRP incubated with heartworms was monitored. Seemingly, platelet activation to heartworm membranes occurs in dogs with heartworm disease. The increased platelet reactivity was also observed in dogs with occult heartworm disease, indicating that the presence of circulating microfilaria was not important for this process. The ability to transfer the reactivity to heartworm-negative platelets by suspending them in heartworm-positive plasma indicated that this reactivity resided in the plasma. The processes leading to platelet activation may be responsible for the platelet-associated vascular disorders of canine heartworm disease.

Adenosine Diphosphate↗

The amino acid sequence of the zinc-requiring beta-lactamase II from the bacterium Bacillus cereus 569.

The amino acid sequence of the zinc-requiring beta-lactamase II from Bacillus cereus strain 569 has been determined. It consists of a single polypeptide chain of 227 residues. It is the only example so far fully characterized of a class B beta-lactamase, and is structurally and mechanistically distinct from both the widely distributed class A beta-lactamases (such as the Escherichia coli RTEM enzyme) and from the chromosomally encoded class C enzymes from Gram-negative bacteria.

Amino Acid Sequence↗

Analysis of chromatin changes associated with the expression of globin and non-globin genes in cell hybrids between erythroid and other cells.

Red blood cell differentiation involves the coordinate expression of a set of polypeptides some of which are erythroid-specific (the abundant globins as well as minor species such as glycophorin, carbonic anhydrase I and the RBC lipoxygenase) whereas others are found also in a subset of other cells, e.g. beta spectrin and a 19 kd polypeptide (ep 19) found in adult liver and kidney as well as erythroid cells. To investigate the genetic mechanisms involved in the regulation of these classes of genes, the expression of lipoxygenase, ep 19 and beta globin mRNAs was investigated in cell hybrids between mouse erythroid (Friend) cells and mouse T-lymphoma or neuroblastoma cells. All three mRNAs are expressed or repressed together in cell hybrids between the Friend cell and lymphoma or neuroblastoma cells respectively. Moreover, studies of the chromatin structure surrounding the genes reveal that erythroid cell-specific DNaseI hypersensitive sites within the ep 19 and beta major globin genes are lost in the Friend cell X neuroblastoma hybrids whereas they are retained in the Friend cell X lymphoma cell hybrids. This implies that the trans-acting mechanism responsible for regulating the RBC phenotype in these cell hybrids acts at the level of the early chromatin changes thought to reflect a pre-activation stage in gene expression.

Animals↗

Insulin or increased concentration of zinc in liver, kidney or muscle does not alter the phosphoglucomutase activity in vivo.

Injection of insulin into mice and rabbit has been reported to convert the latent form of phosphoglucomutase (E X Zn) to an active form (E X Mg) without any net increase in the protein associated with this enzyme (Hashimoto et al., Biochem. Biophys. Res. Commun., 27 (1967) 369 and Peck et al., J. Biol. Chem. 242 (1971) 1160). Because the injection of Cd in rats causes a 2-fold increase in Zn concentration in the liver, it appeared that such treatment in mice would increase the concentration of the latent enzyme and thereby enhance the insulin induced activation of the enzyme. The results however show that insulin or Cd treatment, alone or in combination do not alter the concentrations of the 2 forms of enzyme in liver, kidney or muscle of normal or fasted mice. In all instances the conversion of the latent enzyme to its activated form required preincubation with a chelating agent. Fractionation of the tissue homogenates showed that upon Cd injection the concentration of Zn in the fractions of Mr less and 1000 increased 6-fold in liver and 3-fold in kidney, that in muscle remained unchanged.

Animals↗

Phage pilH alpha: a phage which adsorbs to IncHI and IncHII plasmid-coded pili.

Phage pilH alpha was specific for bacterial strains, of various genera, harbouring plasmids of the HI and HII incompatibility groups. Plaque formation was temperature sensitive in that plaques formed at 26 degrees C but not at 37 degrees C. Plaques were fairly clear, irregular in outline and varied from pin point to about 2 mm in diameter on all hosts where plaques were detected. The phage had an isometric hexagonal outline with a diameter of 25 nm. It contained RNA but differed from all but one other plasmid-dependent RNA phage by being sensitive to chloroform. It adsorbed along the length of the shafts of IncHI and HII plasmid-coded pili.

Adsorption↗

Plasmodium falciparum takes up iron from transferrin.

Plasmodium falciparum, cultured in vitro, is inhibited by desferrioxamine, a specific iron chelating agent, despite the abundant haem iron which surrounds the parasite. In this report we show that the intraerythrocytic parasite obtains iron from transferrin. The parasite may therefore be freed of a requirement to catabolize haem to obtain iron thus minimizing haem toxicity.

Animals↗

Identification of polypeptides on two-dimensional electrophoresis gels by amino acid composition.

We present a method that can, in principle, provide tentative identification of a substantial proportion of the polypeptides resolvable on a given two-dimensional electrophoresis gel. Computerized microdensitometry of autoradiograms from 20 gels labeled in turn with each of the 20 common amino acids provides the data for simultaneously measuring the amino acid composition of all polypeptides of interest on the gel. These compositions are then compared with computer data bases of known protein compositions. Similarity between a known and an unknown polypeptide with comparable molecular mass indicates a potential identification, which can then be confirmed with conventional techniques. We illustrate this technique by applying it to the identification of proteins in a transformed human cell line (HuT-14).

Amino Acids↗

Fetal oxygen consumption, umbilical circulation and electrocortical activity transitions in fetal lambs.

Chronically instrumented fetal lambs were employed to test the hypothesis that the high voltage electrocortical activity phase is a state of low fetal oxygen consumption compared with the low voltage electrocortical activity phase. Measurements of umbilical flow (electromagnetic flowmeter) together with oxygen saturations and haemoglobin concentration of umbilical venous and arterial blood were used to calculate oxygen consumption. Significant depression of umbilical flow occurred at the transition from low voltage electrocortical activity to high voltage electrocortical activity; the maximum change averaged 14% 2 min after the onset of the high voltage phase. Significant depressions of oxygen saturation in umbilical venous and arterial blood were found within 5 min of the onset of high voltage electrocortical activity, averaging 2.2% and 5.2% respectively. No depression of oxygen consumption was found during these transient changes in early high voltage electrocortical activity, as the venous-arterial oxygen content difference widened significantly as a consequence of a greater fall in umbilical arterial oxygen content (0.7 ml/dl) than in umbilical venous oxygen content (0.3 ml/dl). Overall, we detected no significant depression of oxygen consumption in high voltage electrocortical activity. However a small but significant depression of oxygen consumption (6%) was found late in the high voltage electrocortical activity phase when the level of oxygen consumption in low voltage electrocortical activity was greater than 7 ml/min per kg. We conclude that the high voltage electrocortical activity in fetal lambs is not associated with a marked depression of oxygen consumption, despite significant transient depressions of umbilical flow and oxygen levels in umbilical venous and arterial blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A monoclonal antibody against erythrocyte spectrin reacts with both alpha- and beta-subunits and detects spectrin-like molecules in non-erythroid cells.

A panel of nine monoclonal antibodies against the characteristic erythrocyte membrane protein spectrin has been isolated. One antibody reacts with both the 240 000 and 220 000 D alpha- and beta-subunits of spectrin after denaturation. The same antibody reacts with a 240 000 D protein present in various hemopoietic and other cell lines, as well as some smaller polypeptides, as established by western blotting and immunoautoradiography. These results indicate that the alpha- and beta-subunits of spectrin, a polypeptide of 240 000, and some smaller polypeptides present in non-erythroid cell types possess a considerable region of sequence homology, but it is not yet clear just how extensively the spectrin-like molecules and other polypeptides are related.

Amino Acid Sequence↗

The dexamethasone suppression and thyrotropin-releasing hormone tests in depressed borderline patients.

Borderline patients can be both a diagnostic and a therapeutic enigma. We investigated a group of 24 depressed women with borderline personality disorder or strong borderline features by DSM III criteria for the presence of either an abnormal dexamethasone suppression test (DST) or a blunted TSH response to TRH, abnormalities which have been reported in major depression. Thirteen of the 24 borderlines failed to suppress on the DST, compared with one of 14 normal women (p less than 0.01). Nine of the 24 borderlines had a blunted TSH response to TRH, compared with one of 11 normal women. Neuroendocrine abnormalities were found in a total of 75% of the borderline women, independent of whether or not they met DSM III criteria for major depressive disorder. The results of this study support the notion that many borderline patients with depression have a genuine affective component to their illness, perhaps biologically similar to major depression in non-borderlines.

Adolescent↗

Bacteriophage M: an incompatibility group M plasmid-specific phage.

Phage M was specific for bacterial strains, of various genera, harbouring plasmids of the M incompatibility group. It formed turbid plaques which varied from pin point to more than 2 mm in diameter on all hosts where plaques were detected. The phage had an hexagonal outline with a diameter of 27 nm. It contained RNA but differed from other plasmid-dependent RNA phages in being sensitive to chloroform. It adsorbed along the length of shafts of M pili.

Escherichia coli↗

Antioxidants, metabolic rate and aging in Drosophila.

In line with the (metabolic) rate-of-living theory of aging, previous work from this laboratory showed that the life-prolonging effect of the antioxidant thiazolidine carboxylic acid (TCA) in Drosophila was paralleled by a similar reduction of the oxygen consumption rate of the flies. To assess the generality of this phenomenon, several life-prolonging antioxidants were dietarily administered to the flies (in standard medium with 1% w/v of tocopherol-stripped corn oil) and their effects on metabolic rate and life span were determined. Respiration rate of groups of continuously agitated flies was measured in the Gilson respirometer. The studied antioxidants were as follows: (the numbers in parentheses are consecutively the antioxidant concentration in the medium in % wt/vol.; mean life span in days; and metabolic rate in microliter O2/mg fly per 24 h): vitamin E (0.4; 46.3; 58.5); 2,4-dinitrophenol (0.1; 45.7; 66.2); nordihydroguaiaretic acid (0.5; 45.6; 69.1); thiazolidine carboxylic acid (0.3; 53.1; 55.8); and control with no antioxidant added (0; 40.7; 73.3). All of these antioxidants at the tested concentrations reduced oxygen consumption rate and increased mean life span; there was a significant negative linear correlation (r = -0.87) between mean life span and metabolic rate. These data suggest that some antioxidants may inhibit respiration rate in addition to their protective effect against free radical-induced cellular damage.

2,4-Dinitrophenol↗

Effects of simulated increased gravity on the rate of aging of rats: implications for the rate of living theory of aging.

Ever since Pearl proposed the rate of living theory of aging numerous studies have demonstrated its validity in poikilotherms. In mammals, however, satisfactory experimental demonstration is still lacking because an externally imposed increase of basal metabolic rate of these animals (e.g. by placement in the cold) is usually accompanied by general homeostatic disturbance and stress. The present study was based on the finding that rats exposed to slightly increased gravity are able to adapt with little chronic stress but at a higher level of basal metabolic expenditure (increased 'rate of living'). The rate of aging of 17-mth-old rats that had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 mth was larger than of controls as shown by apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration (reduced 'efficiency': 20% larger ADP: 0 ratio, P less than 0.01; reduced 'speed': 8% lower respiratory control ratio, P less than 0.05). On the other hand, steady-state food intake per day per kg body weight, which is presumably proportional to 'rate of living' or specific basal metabolic expenditure, was about 18% higher than in controls (P less than 0.01) after an initial 2-mth adaptation period. Finally, though half of the centrifuged animals lived only a little shorter than controls (average about 343 vs. 364 days on the centrifuge, difference statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for controls, computed from onset of centrifugation, or 11% shorter (P less than 0.01). Therefore, these results show that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.

Aging↗

The head retraction reflex--its specificity in Parkinson's disease.

The head retraction reflex consists of a brief, involuntary extension of the neck on tapping the upper lip. This reflex was found to be present in 17.2% of patients with Parkinson's disease, but in only 4.9% of normal controls and 8% of cases of senile dementia. In addition there was a correlation between the severity of the Parkinson's disease and the presence of the reflex. This suggests that the reflex is specifically related to the Parkinson's disease process rather than to aging or the presence of dementia.

Aged↗