PubMed Health⌕ Search

Biomedical subjects

D A Simmons

Publications and source records attributed to D A Simmons.

At least 19 recordsLinked to original sources
PubMed1992

Mechanisms in rabbit aorta for hyperglycaemia-induced alterations in angiotensin II and norepinephrine effects.

The (Na+,K+)-ATPase activity operative in rabbit aortic intima-media incubated with normal plasma levels of glucose and myo-inositol (70 mumol/l) is decreased when the glucose content of the medium is raised from 5 to 10 mmol/l or higher; this effect is prevented by aldose reductase inhibitors and by raising the myo-inositol content of the medium to 500 mumol/l. The decrease in (Na+,K+)-ATPase activity results from the loss of a component normally regulated (stimulated) by endogenously released adenosine through a receptor that stimulates phosphatidylinositol turnover in a discrete pool. The replenishment of this phosphatidylinositol pool selectively requires myo-inositol transport and is inhibited when increased polyol pathway activity impairs myo-inositol transport at a normal plasma level. Adenosine is a vasodilator, some endothelium-released vasodilators modulate the responses to vasoconstrictors by stimulating an increase in (Na+,K+)-ATPase activity in vascular smooth muscle. Whether adenosine mediates this effect in angiotensin II or norepinephrine-stimulated aorta was examined. Angiotensin II (100 nmol/l) and norepinephrine (1 mumol/l) evoked marked increases in (Na+,K+)-ATPase activity in aortic intima-media incubated with 5 mmol/l glucose and 70 mumol/l myo-inositol, which were inhibited when adenosine deaminase was added or the medium myo-inositol omitted to inhibit myo-inositol transport. Raising the medium glucose to 30 mmol/l inhibited the angiotensin II and norepinephrine-evoked increases in (Na+,K+)-ATPase activity, and this was prevented when tolrestat (10 mumol/l) was added or the myo-inositol content of the medium was raised from 70 to 500 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Elevated extracellular glucose inhibits an adenosine-(Na+,K+)-ATPase regulatory system in rabbit aortic wall.

The mechanism by which hyperglycaemia causes decreased (Na+,K+)-ATPase activity preventable by aldose reductase inhibitors and by raising plasma myo-inositol in specific tissues can be activated in vitro in normal rabbit aortic wall; it selectively inhibits a component of resting (Na+,K+)-ATPase activity maintained by a novel regulatory system through rapid basal phosphatidylinositol turnover (hydrolysis) in a discrete pool, which is replenished by a fraction of phosphatidylinositol synthesis that selectively requires myo-inositol transport. A role for endogenously released adenosine in this regulatory system was examined. Adding adenosine deaminase or 8-phenyltheophylline, an adenosine receptor antagonist, selectively inhibited the component of (Na+,K+)-ATPase activity maintained by the regulatory system; when inhibited with adenosine deaminase this component was restored by 2-chloroadenosine, 5'-N-ethylcarbox-amidoadenosine, and 1-oleoyl-2-acetylglycerol, but not by forskolin (which also did not inhibit this component). Adenosine deaminase inhibited the rapid basal turnover of the discrete phosphatidylinositol pool, and 2-chloroadenosine then stimulated its turnover. Raising medium glucose from 5 to 10-30 mmol/l inhibits the regulatory system by making myo-inositol transport at a normal plasma level inadequate to maintain the replenishment of the discrete phosphatidylinositol pool. 2-Chloroadenosine stimulation of the "adenosine-sensitive" component of (Na+,K+)-ATPase activity was inhibited in tissue incubated with 30 mmol/l glucose and myo-inositol in a normal plasma level, but this effect was demonstrable when the medium myo-inositol was raised seven-fold. Hyperglycaemia-induced decreased (Na+,K+)-ATPase activity that is preventable by aldose reductase inhibitors and by raising plasma myo-inositol results from the inhibition of a novel adenosine-(Na+,K+)-ATPase regulatory system.

2-Chloroadenosine↗
PubMed1991

Protein expression in relation to the cell cycle of exponentially growing human prostatic epithelial cells.

This report concerns the study of the relationship between protein expression and the cell cycle in exponentially proliferating benign and malignant human prostate epithelial cells in short-term cultures. Multiparameter flow cytometric measurements were performed to correlate the expression of prostate-specific acid phosphatase, epithelial membrane antigen and epitectin with cell cycle progression. The expression of the three proteins was heterogeneous in G1 cells. The early post-mitotic cells exhibited the lowest levels when compared with late G1 cells, wherein the expression was many times greater. There was no further increase as the cells progressed through S and G2 + M. These findings, corroborating prior observations in other systems, suggest the possibility that the levels of the proteins studied increase during the G1 phase of the cell cycle and drop during or immediately after cytokinesis. As an alternate explanation, the heterogeneity of protein expression characteristic of G1 cells may be due, at least in part, to an asymmetric apportionment of cell constituents at mitosis.

Acid Phosphatase↗
PubMed1991

Effect of myo-inositol on cell proliferation and collagen transcription and secretion in proximal tubule cells cultured in elevated glucose.

Tubulointerstitial lesions often develop in the kidneys of patients and experimental animals with diabetes mellitus. In an in vitro model of diabetic renal disease, it has been previously demonstrated in this laboratory that elevated glucose levels stimulate procollagen transcription and secretion in proximal tubule cells in culture while inducing cellular hypertrophy and reducing cellular proliferation. Previous experiments in other tissues have suggested that myo-inositol supplementation, probably by reversing a disturbance in cell myo-inositol metabolism related to increased activity of the polyol pathway, reverses the effects of glucose on cell function. We tested the effect of myo-inositol supplementation on proximal tubule cells in culture in the presence of elevated medium glucose level. Incubation in 450 mg/dL of glucose media reduced cell proliferation; 450 mg/dL of glucose plus myo-inositol (800 microM) increased proliferation, returning the value to that seen in cells incubated in 100 mg/dL of glucose. Incubation in 450 mg/dL of glucose media increased type IV and type I procollagen mRNA levels and peptide secretion rates compared with those seen in cells incubated in medium containing 100 mg/dL of glucose. This glucose-induced stimulation of procollagen mRNA levels and procollagen secretion was not observed when the elevated glucose medium was supplemented with 800 microM myo-inositol. On the other hand, myo-inositol supplementation did not prevent the glucose-induced cellular hypertrophy: there was no reduction in the increased leucine incorporation and cellular protein content. Cell incubation in 450 mg/dL of glucose media did not lead to a measurable decrease in total cellular myo-inositol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of polyol-pathway inhibition and dietary myo-inositol on glomerular hemodynamic function in experimental diabetes mellitus in rats.

Early functional disturbances in nerve, retina, and lens in diabetes mellitus appear to result from a common mechanism involving increased polyol-pathway activity with an associated effect on tissue myo-inositol metabolism. We tested the role of increased polyol-pathway activity in the early glomerular hemodynamic abnormalities in experimental diabetes in rats with dietary myo-inositol supplementation or the administration of sorbinil, an aldose reductase inhibitor. Each maneuver prevented the glomerular hyperfiltration of early streptozocin-induced diabetes and reversed the hyperfiltration of established diabetes of 10 days' duration. We also found that the abnormal response to captopril in diabetic rats was improved by dietary myo-inositol supplementation or sorbinil administration. Although nonhypotensive doses of captopril lowered glomerular filtration rate (GFR) in diabetic rats on a 0.01% myo-inositol diet, GFR increased substantially after captopril infusion in diabetic rats treated with sorbinil or myo-inositol supplementation. These data suggest that normalization of tissue myo-inositol metabolism restores normal responsiveness to angiotensin II; this may contribute to the reduction in GFR with the two experimental maneuvers. We also tested the interaction between polyol-pathway activation and high dietary protein intake. Aldose reductase inhibition and dietary myo-inositol supplementation had no effect on the component of increased GFR due to 50% dietary protein intake but specifically inhibited the hyperfiltration attributable to diabetes. These results suggest that hyperglycemia acts through increased polyol-pathway activity and its effects on tissue myo-inositol metabolism to play a fundamental role in the pathogenesis of the glomerular hyperfiltration characteristic of early diabetes.

Animals↗
PubMed1989

Predictive value of DNA measurements in bladder washings. Comparison of flow cytometry, image cytophotometry, and cytology in patients with a past history of urothelial tumors.

Comparative DNA ploidy measurements were carried out by flow cytometry and by image analysis on cells in 71 bladder washing specimens from 50 patients with past histories of bladder tumors. Among the specimens classified as diploid or questionable by flow cytometry, 14 showed the presence of aneuploid DNA values documented by image analysis. In 18 of the 50 patients, recurrent tumors were observed during a relatively brief period of follow-up. In 15 of them the DNA pattern was aneuploid and in three it was questionable. In nine of the 15 patients, both methods of DNA analysis disclosed aneuploidy, but in six patients aneuploidy was detected by image analysis only. A combination of DNA aneuploidy, whether observed by flow cytometry, image analysis, or both, and of positive or suspicious urine cytology is highly predictive of recurrence of high grade bladder tumors. Image analysis of DNA content in bladder washings adds information of clinical value above and beyond that obtained by flow cytometry.

Aged↗
PubMed1989

Mechanism of glucose-induced (Na+, K+)-ATPase inhibition in aortic wall of rabbits.

Hyperglycaemia decreases (Na+, K+)-ATPase activity in specific tissues by a mechanism whose effects are prevented by aldose reductase inhibitors and by raising plasma myo-inositol. This mechanism was activated and studied in vitro in normal rabbit aortic intima-media. Raising medium glucose to 10 mmol/l for 60 min inhibited a major component of (Na+, K+)-ATPase-mediated 86Rb+/K+ uptake normally operative in resting aortic intima-media in medium containing normal plasma levels of glucose (5 mmol/l) and myo-inositol (70 mumol/l); 20 or 30 mmol/l glucose had no greater effect. This effect occurred under conditions in which the aortic intima-media's normal myo-inositol content is not detectably decreased. The inhibition was prevented by sorbinil (10 mumol/l) and by raising medium myo-inositol from 70 to 500 mumol/l, which had no effect on (Na+, K+)-ATPase activity when the medium glucose remained at 5 mmol/l. Raising medium glucose selectively inhibited a component of (Na+, K+)-ATPase activity that requires medium myo-inositol, because it is maintained by a regulatory system through rapid basal phosphatidylinositol turnover in a discrete pool, which is replenished by a fraction of basal de novo phosphatidylinositol synthesis that is selectively dependent on myo-inositol uptake. Medium myo-inositol at a normal plasma level became inadequate to maintain this fraction of basal de novo phosphatidylinositol synthesis [( 1,3-14C]glycerol incorporation) when the medium glucose was raised. When sorbinil was added raising medium glucose did not alter the ability of 70 mumol/l medium myoinositol to maintain the (Na+, K+)-ATPase activity that requires medium myo-inositol.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1989

A selective mapping algorithm for computer analysis of voided urine cell images.

One of the fundamental targets of the automated image analysis of cytologic preparations is the reduction of computer classification errors due to cells or other objects that do not lend themselves to image segmentation or that have morphologic features that may mislead the cell classification schemes. In prior work from this laboratory, the achievement of this goal was attempted by hierarchical analysis of sequential microscopic objects at high resolution. This paper reports on the successful development and implementation of an automated "selective mapping algorithm" that selects cells at low power for further analysis and eliminates a large proportion of unwanted "objects." The algorithm classifies the objects and extracts appropriate features from a 256 X 240 digital image obtained via a 10 X planachromatic objective. The five-node binary tree classifier used in this triage is described. The algorithm was trained and tested initially on 501 visually classified microscopic "objects," resulting in a correct acceptance rate of 61.3% and correct rejection rate of 81.3%. The selective mapping algorithm was subsequently integrated into the video-based image analysis system constructed at the Montefiore Medical Center for the diagnostic evaluation of sediments of voided urine. The algorithm was then tested on ten cytocentrifuge preparations for a preliminary evaluation of its performance. Up to 100 "objects" per case were selected by the algorithm for further classification by the computer at high power. Of the 810 "objects" selected by the selective mapping algorithm, 344 (42.5%) were classified by the computer at high resolution as cells of diagnostic value ("WELL" cells) and 466 were rejected.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1987

Hospital management of a patient with factitial dermatitis.

A 64-year-old male with a 40-year history of dermatologic disorders is presented. The patient carries diagnoses of neurodermatitis and suspected myosis fungoides on which has been superimposed a factitial dermatitis requiring increasingly extended hospitalizations. Given a very disturbed home life and personality style, the patient showed no incentive for change, and his family and caregivers became increasingly frustrated and distraught. An operant behavioral approach proved helpful to staff in standardizing care and setting realistic expectations. This led to a reversal of a downward course and to a coordinated discharge.

Behavior Therapy↗
PubMed1986

Basal phosphatidylinositol turnover controls aortic Na+/K+ ATPase activity.

To determine whether basal phosphoinositide turnover plays a role in metabolic regulation in resting rabbit aortic intima-media incubated under steady state conditions, we used deprivation of extracellular myo-inositol as a potential means of inhibiting basal phosphatidylinositol (PI) synthesis at restricted sites and of depleting small phosphoinositide pools with a rapid basal turnover. Medium myo-inositol in a normal plasma level was required to prevent inhibition of a specific component of basal de novo PI synthesis that is necessary to demonstrate a discrete rapidly turning-over [1,3-14C]glycerol-labeled PI pool. Medium myo-inositol was also required to label the discrete PI pool with [1-14C]arachidonic acid (AA). The rapid basal turnover of this PI pool, when labeled with glycerol or AA, was not attributable to its utilization for polyphosphoinositide formation, and it seems to reflect basal PI hydrolysis. Depleting endogenous free AA with medium defatted albumin selectively inhibits the component of basal de novo PI synthesis that replenishes the rapidly turning-over PI pool. A component of normal resting energy utilization in aortic intima-media also specifically requires medium myo-inositol in a normal plasma level and a free AA pool; its magnitude is unaltered by indomethacin, nordihydroguaiaretic acid, or Ca2+-free medium. This energy utilization results primarily from Na+/K+ ATPase activity (ouabain-inhibitable O2 consumption), and in Ca2+-free medium deprivation of medium myo-inositol or of free AA inhibits resting Na+/K+ ATPase activity to a similar degree (60%, 52%). In aortic intima-media basal PI turnover controls a major fraction of resting Na+/K+ ATPase activity.

Animals↗
PubMed1986

Subungual tumors in incontinentia pigmenti.

A 22-year-old woman presented with intermittently painful subungual keratotic tumors of the hands as a late manifestation of incontinentia pigmenti. Scalloped bony deformities of the distal phalanges of both hands were noted on roentgenograms. The origin of these lytic deformities is uncertain; they may be secondary pressure phenomena or, alternatively, they may be an intrinsic manifestation of incontinentia pigmenti. These subungual tumors clinically resemble verrucae, keratoacanthomas, squamous cell carcinomas, or subungual fibromas. Therefore, it is important to recognize that subungual keratotic tumors may be a late manifestation of incontinentia pigmenti.

Adult↗
PubMed1982

Significance of tissue myo-inositol concentrations in metabolic regulation in nerve.

Approximately 25 percent of resting energy utilization in isolated nerve endoneurium is inhibited by medium containing defatted albumin and selectively restored by arachidonic acid but is unaffected by indomethacin or nordihydroguaiaretic acid. The same component of energy utilization is inhibited by small decreases in endoneurial myo-inositol, which decrease incorporation of carbon-14-labeled arachidonic acid into phosphatidylinositol. The fraction of the resting oxygen uptake inhibited by ouabain is decreased 40 to 50 percent by a reduced tissue myo-inositol concentration or by defatted albumin. Metabolic regulation by rapid, basal phosphatidylinositol turnover is dependent on the maintenance of normal tissue myoinositol concentrations.

Albumins↗