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Biomedical subjects

R Strong

Publications and source records attributed to R Strong.

At least 37 records · Page 2Linked to original sources
PubMed1989

Phosphorylation of ferredoxin and regulation of renal mitochondrial 25-hydroxyvitamin D-1 alpha-hydroxylase activity in vitro.

The kidney is the principal physiologic site of production of biologically active 1,25-dihydroxyvitamin D. The 25-hydroxyvitamin D-1 alpha-hydroxylase (1-OHase) activity found in renal mitochondria is under tight hormonal control. Parathyroid hormone stimulates the renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D in young animals, which is accompanied by dephosphorylation of ferredoxin (Fx), a component of the mitochondrial 1-OHase enzyme complex (Siegel, N., Wongsurawat, N., and Armbrecht, H. J. (1986) J. Biol. Chem. 261, 16998-17003). The present study investigates the capacity of Fx to be phosphorylated in vitro and to modulate the 1-OHase activity of a reconstituted system. Fx was phosphorylated by renal mitochondrial type II protein kinase. Phosphorylation did not alter Fx mobility on sodium dodecyl sulfate gels but did decrease the pI as measured by isoelectric focusing. Amino acid analysis demonstrated that 1 mol of serine and 1 mol of threonine were phosphorylated per mol of Fx. Peptide mapping of phosphorylated Fx was consistent with phosphorylation of serine 88 and threonine 85 or 97. Fx was selectively dephosphorylated by rabbit skeletal muscle protein phosphatase C2 but not C1. Phosphorylation of Fx significantly inhibited the 1-OHase activity of a reconstituted system consisting of Fx reductase, Fx, and renal mitochondrial cytochrome P-450. These findings suggest that phosphorylation/dephosphorylation of Fx may play a role in modulating renal 1,25-dihydroxyvitamin D production.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1989

The effect of aging and dietary restriction on DNA repair.

DNA repair was studied as a function of age in cells isolated from both the liver and the kidney of male Fischer F344 rats. DNA repair was measured by quantifying unscheduled DNA synthesis induced by UV irradiation. Unscheduled DNA synthesis decreased approximately 50% between the ages of 5 and 30 months in both hepatocytes and kidney cells. The age-related decline in unscheduled DNA synthesis in cells isolated from the liver and kidney was compared in rats fed ad libitum and rats fed a calorie-restricted diet; calorie restriction has been shown to increase the survival of rodents. The level of unscheduled DNA synthesis was significantly higher in hepatocytes and kidney cells isolated from the rats fed the restricted diet. Thus, calorie restriction appears to retard the age-related decline in DNA repair.

Aging↗
PubMed1989

Immunohistochemical determination of calcium-calmodulin binding predicts neuronal damage after global ischemia.

Since ionic Ca2+ binds with intracellular calmodulin (CaM) before activating proteases, kinases, and phospholipases, demonstration of persistent Ca2+-CaM binding in neurons destined to show ischemic cellular injury would support the concept that elevated intracellular Ca2+ plays a causative role in ischemic neuronal damage. In order to characterize Ca2+-CaM binding, we used a sheep anti-CaM antibody (CaM-Ab) which recognizes CaM that is not bound to Ca2+ or brain target proteins. Therefore, immunohistochemical staining of brain sections by labeled CaM-Ab represented only unbound CaM. Six normal rats were compared to 15 animals rendered ischemic for 30 min by a modification of the four-vessel occlusion model. Animals were killed immediately after ischemia, and after 2 and 24 h of reperfusion. Brain sections through hippocampus were incubated in CaM-Ab, and a diaminobenzadiene labeled anti-sheep secondary antibody was added to stain the CaM-Ab. Staining in the endal limb of dentate, dorsal CA1, lateral CA3, and parietal cortex was graded on a 4-point scale. All normal animals had grade 4 staining indicating the presence of unbound CaM in all four brain regions. Ischemic animals demonstrated reduced (grade 0 to 2) staining in the CA1 and CA3 regions immediately and 2 and 24 h after ischemia (p less than 0.01 for both regions at all three time intervals) indicating persistent binding of CaM with Ca2+ and target proteins in these regions. Staining decreased in dentate and cortex up to 2 h after ischemia (p = 0.02 for both regions) but returned toward normal by 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Expression of calbindin-D decreases with age in intestine and kidney.

The calbindins are Ca-binding proteins whose expression is regulated by 1,25-dihydroxyvitamin D3, the active metabolite of vitamin D3. The calbindins are found in high amounts in the proximal intestine (calbindin-D-9k) and the kidney (calbindin-D-28k), and they are thought to play a role in Ca transport by these tissues. Ca absorption by the intestine and perhaps the kidney declines with age, and this could be due to decreased expression of calbindin. Therefore, the expression of calbindins-D-9k and -D-28k was measured in F344 rats aged 2, 6, 13, and 24 months. mRNA levels were measured by dot blot hybridization to synthetic cDNA oligonucleotide probes, and protein levels were measured by enzyme-linked immunosorbent assay using specific antisera. Intestinal calbindin-D-9k mRNA decreased markedly between 2 and 6 months of age, but it then increased significantly between 13 and 24 months. Calbindin-D-9k protein paralleled the decrease in mRNA between 2 and 6 months, but continued to decline at 13 and 24 months despite the rise in mRNA. In the kidney, calbindin-D-28k mRNA declined between 2 and 13 months and then plateaued. Calbindin-D-28k protein followed a similar pattern. In the same studies expression of calmodulin by the intestine and kidney did not change with age. Plasma 1,25-dihydroxyvitamin-D3 correlated well with the expression of calbindin-D-9k in the intestine at 2 and 6 months of age and with the expression of calbindin-D-28k in the kidney at all ages. Decreased expression of calbindin-D with age may contribute to the age-related decrease in Ca transport in intestine and kidney.

Aging↗
PubMed1988

Evidence for retrograde degeneration of epinephrine neurons in Alzheimer's disease.

Alzheimer's disease (AD) is associated with a progressive loss of locus ceruleus neurons. These noradrenergic neurons receive a major afferent projection from epinephrine neurons in epinephrine cell groups in the brainstem. The epinephrine neurons have a specific enzymatic marker, phenylethanolamine N-methyltransferase (PNMT), which allows them to be identified chemically and immunohistochemically. We have previously reported a decrease in PNMT in brains of patients with AD. We now report that the decrease in PNMT activity in projections to the locus ceruleus is not due to the loss of epinephrine neurons, although up to 33% of these neurons are atrophic. The decrease in presynaptic PNMT does, however, correlate with the loss of postsynaptic locus ceruleus neurons in brains from AD patients. The percentage of degenerating neurons in the epinephrine nuclei also correlates significantly with the amount of loss of locus ceruleus neurons in AD. In addition, there is a 55% decrease in mitogen activity, a nonspecific measure of growth or maintenance factors, in dialysed locus ceruleus extracts from the AD patients compared to those from control subjects. The mitogen activity in the locus ceruleus was significantly correlated with PNMT activity and with the density of locus ceruleus neurons in all cases examined. These findings provide evidence for the hypothesis that retrograde degeneration is a mechanism of neuronal degeneration in AD and suggest that trophic factors may play a role in this process.

Aged↗
PubMed1988

Modulation of age-related changes in serum 1,25-dihydroxyvitamin D and parathyroid hormone by dietary restriction of Fischer 344 rats.

The purpose of this study was to determine the effect of food restriction on age-related changes in serum 1,25-dihydroxyvitamin D and PTH, two important regulators of Ca metabolism. Starting at 6 wk, male F344 rats were fed a purified diet either ad libitum (non-restricted) or 60% of ad libitum (restricted). Rats from each group were killed at 5, 13, 22 and 28 mo of age. Dietary restriction increased the median lifespan from 24 to 31 mo. It delayed the rapid decrease in serum 1,25-dihydroxyvitamin D from 1.5-5.0 mo in the non-restricted group to 5-13 mo in the restricted group. It also completely suppressed the marked rise in serum PTH which occurred at 22 and 28 mo in the non-restricted group. Dietary restriction had these effects even though both groups of animals consumed the same amount of Ca per gram body weight. Diet had no effect on serum Ca and P, except at 28 mo. These effects of dietary restriction on serum 1,25-dihydroxyvitamin D and PTH may result in altered Ca metabolism in dietary restricted F344 rats.

Aging↗
PubMed1988

Regionally selective manifestations of neostriatal aging.

Presynaptic and postsynaptic markers of the cholinergic and dopaminergic systems have characteristic topographical distributions within the striatum. Aside from the dopaminergic afferents, several other afferent systems exhibit a heterogeneous distribution in the striatum. The net result is that each part of the striatum receives a specific and unique combination of afferents. Moreover, the intrinsic striatal systems also have unique distributions, so each part of the striatum consists of a unique combination of afferent and intrinsic neurotransmitter systems. In view of these points, one may expect that the striatum is functionally very complex, integrating information from a wide variety of brain areas. One may also assume from these facts that the striatum is a functionally heterogeneous structure. Consistent with that conclusion, behavioral and pharmacological studies show that interruption of neurotransmission in localized regions of the striatum produces very specific behavioral and physiological effects. Age-related neurochemical changes are also confined to specific striatal regions. Which regions are affected will depend on a variety of factors, including the neurochemical parameter studied and the species or strain of animal. However, we still do not know what factors make a particular striatal area vulnerable to the effects of aging or disease. Moreover, a question that remains to be answered is whether the regions that are affected by neurodegenerative diseases are the same ones affected during normal aging. If so, then this may provide a clue as to why neurodegenerative diseases of the basal ganglia increase in frequency with advancing age. Nevertheless, discrete regional neurochemical alterations may underlie specific symptoms of these diseases. Further study of this relationship may provide the basis for treatments that better target the source of the symptoms. Not only would this increase the effectiveness of the treatment, it would help reduce potential side effects. This may be particularly important, for example, with respect to the use of tissue explants in the treatment of diseases of the basal ganglia.

Aging↗
PubMed1988

Effect of flow on O2 consumption during progressive hypoxemia.

Rabbit hindlimb preparations perfused with blood from donor rabbits were used to determine whether O2 consumption (VO2) during hypoxemia is limited by total O2 transport (TO2) or by capillary O2 driving pressure, as reflected by the venous PO2 (PVO2). The preparations were randomized into two groups: low flow (LF) and high flow (HF), perfused at 18 and 32 ml.min-1.kg of preparation wt-1, respectively. After a 1-h base-line period with arterial PO2 (PaO2) greater than 100 Torr, both groups were exposed to progressive decrements in PaO2 to less than 10 Torr. Sequential sets of arterial and venous blood gases were obtained, and VO2, TO2, and O2 extraction ratio (ERO2) were calculated. A plot of PVO2 vs. TO2 showed higher levels of PVO2 (P less than 0.05) in LF than HF, when compared at similar levels of TO2. Therefore the experimental protocol allowed the comparison of the separate effects of TO2 or PVO2 on VO2. Plotting VO2 as a function of TO2 revealed two distinct curves (P less than 0.05), with LF having a greater VO2 than HF at a given TO2. Conversely, a plot of VO2 as a function of PVO2 did not show a difference between the groups. The ERO2 of LF was greater than HF when compared at similar levels of TO2 (P less than 0.05). We conclude from these data that during progressive hypoxemia VO2 appears to be primarily limited by factors that determine capillary O2 diffusion. This conclusion supports the Kroghian theory of capillary O2 exchange.

Animals↗
PubMed1988

Bioenergetics of rabbit skeletal muscle during hypoxemia and ischemia.

A blood-perfused rabbit hindlimb preparation was exposed to total ischemia (n = 4) or to severe hypoxemia (n = 4) where arterial PO2 was 5 +/- 2 (SE) Torr. O2 consumption (VO2), O2 transport (TO2), venous PO2 (PVO2), venous lactate concentration, and venous glucose concentration were measured. The relative concentration of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH (pHi) were monitored with 31P magnetic resonance spectroscopy. PCr/Pi decreased with the onset of ischemia or hypoxemia. The preparation was reoxygenated and allowed to recover for 30 min once PCr/Pi was less than 1.0. The periods of hypoxemia and ischemia lasted 56.0 +/- 10.0 and 63.8 +/- 2.5 min, respectively (NS). During ischemia PCr decreased and Pi increased compared with control (P less than 0.05) but returned to control with reperfusion. With hypoxemia PCr also decreased and Pi increased with respect to control (P less than 0.01) but did not recover with reoxygenation. VO2 and PVO2 in both groups returned to control during recovery. ATP did not change with ischemia but decreased with hypoxemia (P less than 0.05). Venous lactate concentration did not change with ischemia but increased with hypoxemia (P less than 0.05) and continued to rise during recovery. During recovery pHi decreased in the hypoxemic group (P less than 0.05) but not in the ischemic group. These data show that, under the conditions tested, rabbit skeletal muscle does not resynthesize PCr after a severe hypoxemic episode. Furthermore it appears that VO2 and PVO2 fail to portray the true state of cellular bioenergetics after a severe hypotemic insult.

Adenosine Triphosphate↗
PubMed1988

A new method of segmental orthotopic liver transplantation in children.

Orthotopic liver transplantation requires matching of the donor and recipient for size. The rarity of suitable pediatric and infant donors in many countries has resulted in the acceptance of the principle of a reduced-sized adult liver graft for children. A new method of segmental orthotopic liver transplant is described. This method involves resecting the recipient liver off the inferior vena cava, which is left in situ, and the donor hepatic vein is anastomosed end to side to the inferior vena cava. The technique allows orthotopic liver transplantation with widely mismatched sizes from adults to infants.

Anastomosis, Surgical↗
PubMed1987

Foramen of Winslow hernia.

Two cases of caecal herniation through the foramen of Winslow are presented. The diagnosis was made at laparotomy, but could have been suspected from the clinical features and plain abdominal X-rays. Early operative intervention is the key to avoiding strangulation and the high mortality associated with this uncommon internal hernia.

Adult↗
PubMed1987

Smooth muscle tumours of the upper gastrointestinal tract.

Forty-six patients with smooth muscle tumours of the stomach and small intestine were treated surgically at the Princess Alexandra Hospital between 1970 and 1986. Leiomyomas were three times more common than leiomyosarcomas, but malignant tumours occurred more frequently in the small intestine than in the stomach. Gastric tumours tended to present with gastrointestinal bleeding, in contrast to intestinal lesions which presented predominantly with abdominal pain. Although leiomyomas tend to be smaller at operation than leiomyosarcomas, the size of a smooth muscle tumour is not reliable in discriminating between benign and malignant lesions. Therefore all smooth muscle tumours of the upper gastrointestinal tract should be excised as widely as possible, including local lymphatics in the dissection where practicable, so as to maximize the likelihood of radical extirpation of malignant lesions. Approximately one-third of patients with leiomyosarcomas have metastases at the time of surgery; the 5 year survival rate after surgical treatment of leiomyosarcomas of the upper gastrointestinal tract is less than 50%.

Adolescent↗
PubMed1987

In vitro effects of ethanol on erythrocyte membrane fluidity of alcoholic patients: an electron spin resonance study.

Chronic ethanol consumption has been shown to affect physical properties of membranes from animals as measured by electron spin resonance (ESR). This study compared for the first time the physical properties of erythrocyte membranes of alcoholic patients and control subjects using ESR procedures. Membrane fluidity was determined in the presence and absence of ethanol using the 5-doxyl stearic acid spin-label. Temperature-dependent phase transition also was determined, as were comparisons between ESR parameters, at the 1st and 5th week after alcohol withdrawal. Ethanol-induced fluidity was significantly greater in membranes of control subjects compared with alcoholic patients. Baseline fluidity did not differ and the temperature at which the phase transition occurred was not significantly different between the two groups. The resistance of membranes of alcoholic patients to fluidization by ethanol was unchanged after 5 weeks of withdrawal. Comparisons between ethanol-induced fluidization at the 1st and 5th week after withdrawal were not significantly different. These studies demonstrate differences in ethanol-induced fluidization between alcoholic patients and control subjects that are consistent with earlier ESR studies using an animal model.

Adult↗
PubMed1987

Effects of ethanol on acetylcholine and GABA release: differences in the role of potassium.

Ethanol inhibited electrically stimulated [3H]ACh release from cortical brain slices, but not when release was stimulated by high potassium. In contrast, ethanol was ineffective on electrically stimulated release of [14]GABA from cortical brain slices, but inhibited potassium-induced release. Ethanol also significantly inhibited potassium-stimulated [14C]GABA release from cortical synaptosomes. These data suggest that ethanol selectively inhibits GABA release from neurons by a specific effect on potassium conductance, and inhibits ACh release by a selective effect on Na+ conductance.

Acetylcholine↗
PubMed1987

Chronic ethanol effect on the acidic phospholipids of synaptosomes isolated from cerebral cortex of C57BL/6NNIA mice--a comparison with age.

A total of six groups of C57BL/6NNIA male mice at 6, 18 and 28 months of age were administered a liquid diet containing either ethanol (8 g/kg body wt/day) or an isocaloric amount of glucose for three weeks. Sixteen hours after the last ethanol feeding, homogenates of cerebral cortices were prepared for isolation of the synaptosome-mitochondrial fraction. Phospholipids were separated by two-dimensional tlc and the level of individual phospholipids was determined by assaying the lipid phosphorus content. Based on protein content, there was a decrease (18%) in the level of phosphatidylserines between samples from 6 and 28 month-old mice; no age difference was observed in other phospholipids. Ethanol consumption resulted in a three-fold increase in poly-phosphoinositide level in the 6 month-old group, but the difference diminished considerably with age. The increase in poly-phosphoinositide level suggests a link between chronic ethanol administration and the receptor-mediated signal transduction mechanism involving phosphoinositide turnover. Results further indicate that animals in the younger age group are more readily influenced by the chronic effect of ethanol than those in the older age group.

Aging↗
PubMed1986

Fluidizing effects of centrophenoxine in vitro on brain and liver membranes from different age groups of mice.

This study examined the effects of different concentrations of centrophenoxine on physical properties of synaptic plasma membranes and liver microsomes using electron spin resonance procedures. Membranes of different age groups of mice were labeled with the 5-doxyl stearic acid spin-label and membrane fluidity determined in the presence and absence of different concentrations of centrophenoxine. Centrophenoxine had a direct effect on membranes as shown by a significant increase in membrane fluidity. This effect was greatest in liver microsomes as compared to synaptic plasma membranes. Age differences were not observed in centrophenoxine-induced fluidization. Effects of centrophenoxine in vivo may be due in part to the drug acting directly on the physical properties of the membrane lipid environment.

Aging↗