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Biomedical subjects

J Downey

Publications and source records attributed to J Downey.

At least 55 records · Page 3Linked to original sources

A simple technique for studying struvite crystal growth in vitro.

Struvite urolithiasis forms as a consequence of a urinary tract infection by urease-producing species of bacteria such as Proteus mirabilis. Ammonia, produced by the enzymatic hydrolysis of urea, elevates urine pH causing a supersaturation and precipitation of Mg++ as struvite (NH4MgPO4). Calcium often precipitates as well, forming the mineral carbonate-apatite (Ca10(PO4)6CO3). We have developed a procedure based on direct observation by light microscopy whereby struvite crystal growth can be quickly monitored in response to chemical changes in urine. As struvite crystals assume a characteristic shape or crystal habit based on their growth rate, the effect of urine chemistry and the action of various crystallization or urease inhibitors on struvite formation can be quickly shown. In addition preliminary effects of alkaline pH, or the presence of toxic compounds on bacteria can also be shown through their loss of motility.

Crystallization↗

Influence of chondroitin sulfate, heparin sulfate, and citrate on Proteus mirabilis-induced struvite crystallization in vitro.

Struvite crystals were produced by Proteus mirabilis growth in artificial urine, in the presence of a number of naturally occurring crystallization inhibitors. The use of phase contrast light microscopy enabled the effects of added chondroitin sulfate A, chondroitin sulfate C, heparin sulfate, or sodium citrate, on struvite crystal growth rates to be rapidly monitored as changes in crystal habit. Struvite crystals formed as a consequence of the urease activity of P. mirabilis under all chemical conditions. In the absence of inhibitor, early crystal development was marked by large quantities of amorphous precipitate, followed immediately by the appearance of rapidly growing X-shaped or planar crystals. Addition of the glycosaminoglycans, chondroitin sulfate A, chondroitin sulfate C, or heparin sulfate to the artificial urine mixture had no effect on the rate of crystal growth or appearance. When sodium citrate was present in elevated concentrations, crystal appearance was generally slowed, and the crystals assumed an octahedral, slow growing appearance. None of the added compounds had any influence on bacterial viability, pH, or urease activity. It is therefore likely that the inhibitory activity displayed by sodium citrate might be related to its ability to complex magnesium or to interfere with the crystal structure during struvite formation. From these experiments it would appear that citrate may be a factor in the natural resistance of whole urine to struvite crystallization.

Chondroitin Sulfates↗

Mood disorders, psychiatric symptoms, and distress in women presenting for infertility evaluation.

Women who undergo treatment for infertility frequently report depression, but it is crucial to distinguish between subjective distress, symptoms, and clinical depressive disorders. In the initial assessment of a prospective, longitudinal study, 59 women presenting for infertility treatment were compared with 35 women presenting for routine gynecological care. Infertility patients and controls were not significantly different on self-report measures of partner satisfaction, sexual functioning, or self-esteem. There was also no difference in psychiatric symptomatology, or in the percentage of subjects who were currently experiencing or had ever experienced a major depressive episode. However, the infertility patients perceived themselves to have been already quite affected by their inability to conceive. For instance, 49.2% reported changes in their sexual functioning and 74.6% reported changes in their mood.

Adolescent↗

Psychopathology and social functioning in women with Turner syndrome.

Turner syndrome (TUS) in women is associated with sex chromosome abnormalities, ovarian dysgenesis with estrogen deficiency, and short stature. The goal of this study was to assess the long-term effects of these sex chromosome and hormonal anomalies on psychopathology and social functioning. We report interview and questionnaire data concerning lifetime history of mental disorders and current psychiatric symptoms. Also reported are data from questionnaires and interviews evaluating social functioning as measured by education, occupation, personal resources, and sexual behavior. Twenty-three TUS women were studied and compared with 23 closely matched women with constitutional short stature (CSS) and with 10 normal sisters of the TUS women. TUS women reported generally less mental disorder and comparable rates of psychiatric symptoms. On the other hand, they had lower overall functioning on a measure of global psychological health and had more impairment in social functioning as measured by achievement of adult milestones. We conclude that TUS women display less mental illness by positive symptom-oriented criteria but also less mental health when day-to-day functioning is considered. Our data suggest that differences in TUS women cannot be explained solely by short stature and may be related to other psychosocial, genetic, endocrine, or CNS effects of the syndrome.

Achievement↗

Sex hormones in lesbian and heterosexual women.

The authors measured plasma testosterone (T), androstenedione (A), and cortisol (C) levels in seven lesbian and seven heterosexual women matched for age and socioeconomic status. In addition, psychiatric symptoms, physical activity levels, depression, subjective sense of stress, and sexual behavior variables were assessed. There were no significant differences in sex hormone levels between the two groups of women, who were also comparable in psychiatric symptom levels, depression, and self-perceived stress. Lesbian women reported significantly more current physical activity relative to peers. Other than the sexual orientation difference which was a prerequisite for entry into the study, there were virtually no significant differences in sexual behavior although lesbian women tended to have achieved psychosexual milestones at a younger age. We were not able to corroborate the finding of Gartrell, Loriaux, and Chase (1977) that lesbian women have higher T levels, possibly due to the fact that the two groups were closely matched on several behavioral variables potentially affecting testosterone levels.

Adult↗

Magnesium deficiency and myocardial infarct size in the dog.

Although epidemiologic data suggest a relation between myocardial infarction death rates and dietary intake of magnesium, there are no experimental studies reflecting such a phenomenon. It is now reported that beagle dogs kept on a severely magnesium-deficient diet for 100 days develop a larger infarct than do control animals. Control animals were either kept on the same diet as experimental animals with supplementary magnesium, or were fed standard dog chow. The control groups were indistinguishable and were therefore pooled. Infarction was produced by occlusion of the left anterior descending coronary artery for 1 hour followed by 4 hours of reperfusion. Slices of ventricular myocardium, 5 mm thick, were made from the apex to the base. Ischemic muscle, considered to be the muscle at risk, was delineated by a microsphere-autoradiographic method, and necrotic muscle was delineated by tetrazolium stain. Involved areas were measured by planimetry, and these integrated to produce the volume. The volumes of muscle made ischemic were similar in the experimental and control groups. The volumes of necrotic muscle, however, were less in the control than in the experimental animals. The ratio of necrotic muscle volume to the volume of muscle at risk was greater in the experimental animals than in the control animals by a factor of almost two (p less than 0.004). These experiments indicate that, under the conditions used here, animals fed a magnesium-deficient diet develop a larger infarct than do control animals. This could occur either through decreased postocclusion collateral flow or increased vulnerability of the ischemic muscle in magnesium-deficient animals. Although these experiments cannot rule out an effect on postocclusion collateral flow, they do suggest that electrolyte abnormalities related to magnesium deficiency are of such a character as to increase myocardial vulnerability to injury.

Animals↗

Rat prostatic acid phosphatase: androgenic control of isoelectric focusing patterns.

To further characterize the androgen dependence of prostatic acid phosphatase (AP), the isoelectric focusing patterns of enzyme activity have been examined for normal and castrated adult rats and for rats receiving androgen injections. Isoelectric focusing was performed in polyacrylamide gels over the pH range 4-8. Naphthyl phosphate was used as substrate for staining. For normal rats there was a single lysosomal band (isoelectric point(pI) = 7.35 +/- 0.04), four closely migrating secretory bands (pI = 5.96-5.63), and an androgen-dependent band (pI = 6.37 +/- 0.05) which as yet has not been identified as either lysosomal or secretory. Following castration the secretory bands decreased significantly in staining intensity, the androgen-dependent band disappeared, and two new lysosomal bands (pI's = 7.13 +/- 0.03 and 7.00 +/- 0.03) appeared. With androgen replacement the latter two bands disappeared, the androgen-dependent band reappeared, and the secretory bands increased in staining intensity but with the most anodic of the four appearing before the others. This suggests that it could be a precursor to the others. The isoelectric focusing patterns of AP activity appear to be a better method of assessing the androgen status of the prostate than are the previously used parameters, namely, enzyme specific activity, degree of inhibition by tartrate, and polyacrylamide gel electrophoretic pattern.

Acid Phosphatase↗

A microcomputer-based drop counter.

A microcomputer-based drop counter is described that allows the accurate measurement of fluid flows up to about 5 ml/min. Detailed construction information is included. Unlike most previously described drop counters, it displays flow directly in ml/min and calculates a confidence limit for the measurement.

Blood Flow Velocity↗

Regulatory properties of the ADPglucose pyrophosphorylase from Rhodopseudomonas sphaeroides and from Rhodopseudomonas gelatinosa.

The ADPglucose pyrophosphorylases from Rhodopseudomonas sphaeroides and Rhodopseudomonas gelatinosa are activated by fructose-6-phosphate, pyruvate and fructose-1,6 biophosphate-P2. The effects of the activators are to increase significantly the Vmax of ADPglucose synthesis and to lower the S0.5 values (concentration of substrates giving 50% maximal velocity) for ATP and MgCl2. The R. sphaeroides enzyme is inhibited by Pi while the R. gelatinosa enzyme is inhibited by AMP as well as by Pi. The interaction between inhibitor and activator is complex. At very low concentrations of activator the enzyme is more sensitized to inhibition. However, at higher concentrations of activator there is a decrease in the sensitivity of the enzyme towards inhibition. The findings are discussed with respect to glycogen synthesis in these microorganisms and may be related to findings that indicate that Rhodopseudomonads have the ability to degrade sugars via the Entner-Duodoroff or Embden-Meyerhoff pathways.

Adenosine Diphosphate Glucose↗

Contribution of myocardial contractility to myocardial perfusion.

Myocardial contractility in open-chest anesthetized (sodium pentobarbital) dogs was varied while ventricular pressure, coronary perfusion pressure, and coronary tone were held constant. Under those conditions, changes in regional blood flow should reflect changes only in intramyocardial compression related to the altered inotropic state. Increasing contractility with isoproterenol caused flow to decrease in the outer myocardial layers without change at the subendocardium. When contractility was decreased with pentobarbital, flow at the subendocardium was increased with little change in the outer layers. By manipulating perfusion pressure in the latter experiments it was demonstrated that subendocardial compression was falling from a starting value that was somewhat above peak ventricular pressure.

Animals↗

Accumulation of technetium-99m stannous pyrophosphate in contused myocardium.

The uptake of technetium-99m stannous pyrophosphate in contused myocardium was measured as a function of time from the insult. The free wall of the dog's left ventricle was surgically exposed and struck with a spring-loaded paddle. Pyrophosphate was injected intravenously from 1 1/2 to 47 1/2 hr after the injury. After 1/2 hr of incubation the hearts were removed and the Tc-99m content of contused and noncontused myocardium was measured. Pyrophosphate was concentrated in contused myocardium at all of the time periods tested. Contused-to-normal ratios for pyrophosphate uptake ranged from 8.1 (8 hr) to 41.9 (48 hr).

Animals↗

Kinetic properties of Serratia marcescens adenosine 5'-diphosphate glucose pyrophosphorylase.

The regulatory properties of partially purified adenosine 5'-diphosphate-(ADP) glucose pyrophosphorylase from two Serratia marcescens strains (ATCC 274 and ATCC 15365) have been studied. Slight or negligible activation by fructose-P2, pyridoxal-phosphate, or reduced nicotinamide adenine dinucleotide phosphate (NADPH) was observed. These compounds were previously shown to be potent activators of the ADPglucose pyrophosphorylases from the enterics, Salmonella typhimurium, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Escherichia aurescens, Shigella dysenteriae, and Escherichia coli. Phosphoenolpyruvate stimulated the rate of ADPglucose synthesis catalyzed by Serratia ADPglucose pyrophosphorylase about 1.5- to 2-fold but did not affect the S0.5 values (concentration of substrate required for 50% maximal stimulation) of the substrates, alpha-glucose-1-phosphate, and adenosine 5'-triphosphate. Adenosine 5'-monophosphate (AMP), a potent inhibitor of the enteric ADPglucose pyrophosphorylase, is an effective inhibitor of the S. marcescens enzyme. ADP also inhibits but is not as effective as AMP. Activators of the enteric enzyme counteract the inhibition caused by AMP. This is in contrast to what is observed for the S. marcescens enzyme. Neither phosphoenolpyruvate, fructose-diphosphate, pyridoxal-phosphate, NADPH, 3-phosphoglycerate, fructose-6-phosphate, nor pyruvate effect the inhibition caused by AMP. The properties of the S. marcescens HY strain and Serratia liquefaciens ADPglucose pyrophosphorylase were found to be similar to the above two S. marcescens enzymes with respect to activation and inhibition. These observations provide another example where the properties of an enzyme found in the genus Serratia have been found to be different from the properties of the same enzyme present in the enteric genera Escherichia, Salmonella, Shigella, Citrobacter, and Enterobacter.

1,4-alpha-Glucan Branching Enzyme↗

Compression of the coronary arteries by the fibrillating canine heart.

We performed experiments to test whether the subendocardial ischemia which reportedly accompanies elective ventricular fibrillation (VF) during cardiopulmonary bypass might be the result of mechanical compression of the coronary vessels. The left coronary artery of the open-chest, anesthetized dog was cannulated and perfused with arterial blood through an extracorporeal circuit. Coronary inflow rate was held constant with a pump and the coronary vessels were dilated maximally by infusing adenosine. Any change in perfusion pressure or the transmural distribution of flow in these hearts would have been due to changes in compression. When the hearts were stopped in diastole by vagal stimulation, infusion of microspheres 15 mum in diameter revealed a subendocardial to subepicardial (inner to outer) flow ratio (I/O) of 1.2. When the same hearts were caused to fibrillate spontaneously (not electrically maintained) the I/O fell to 0.9. Little change in coronary perfusion pressure occurred between arrest and VF. When the contractile activity during VF was attenuated by intracoronary sodium pentobarbital (120 mg) the I/O rose toward that seen during arrest. However, augmentation of muscle activity by infusion of isoproterenol during VF failed to change the I/O. Finally the I/O fell in proportion to the degree of distention in the fibrillating ventricle. The results that we observed indicate that muscular contraction during VF preferentially inhibits subendocardial flow through vascular compression.

Adenosine↗