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Biomedical subjects

J E Clark

Publications and source records attributed to J E Clark.

At least 19 recordsLinked to original sources
PubMed1992

Cloned, expressed rat cerebellar nitric oxide synthase contains stoichiometric amounts of heme, which binds carbon monoxide.

The endogenous formation of nitric oxide (NO) has become an area of intense interest as evidence for its biological functions has been obtained in three distinct tissues: circulating macrophages, in which it exerts cytotoxic effects; blood vessels, in which it has been identified as endothelium-derived relaxing factor; and neuronal cells, in which it functions as a neurotransmitter. The formation of NO in brain extracts has been shown to be catalyzed by an enzyme, termed NO synthase, which generates the NO responsible for stimulation of cGMP formation, the highest levels of which occur in the cerebellum. NO synthase catalyzes the formation of citrulline from arginine with the coincident production of NO and has been shown to be a flavoprotein, containing 1 mol each of FAD and FMN, tetrahydrobiopterin, and iron. It is also reported to contain an alpha-helical, calmodulin-binding consensus sequence consistent with its stimulation by calmodulin in the presence of Ca2+. The formation of NO requires incorporation of one of the atoms of molecular oxygen into one of the guanidinium nitrogen atoms of arginine with the coincident formation of citrulline. This communication reports that rat cerebellar NO synthase, cloned and stably expressed in human kidney 293 cells, contains heme in amounts stoichiometric with the flavins FAD and FMN as evidenced by the appearance of a pyridine hemochrome and a reduced CO difference spectrum with an absorbance maximum at approximately 445 nm. The finding of a CO-binding heme moiety explains the presence of iron in the enzyme and suggests a role for prosthetic heme as an oxygenase reaction center. This report also presents evidence for incorporation of delta-[14C]aminolevulinate specifically into immunoprecipitable NO synthase in stably transfected human kidney 293 cells but not in nontransfected cells. Simultaneously, K. A. White and M. A. Marletta [(1992) Biochemistry 31, 6627-6631] have demonstrated a CO-binding heme prosthetic group in purified murine macrophage NO synthase and have suggested the identity of these reaction centers in both the constitutive (cerebellar) and inducible (macrophage) forms of NO synthase.

Amino Acid Oxidoreductases↗
PubMed1991

Bilateral renal hemangiopericytoma.

The first reported case of bilateral renal hemangiopericytoma is presented. The 19 previous renal hemangiopericytomas that have been reported in the world literature are reviewed. This lesion has afflicted patients ranging in age from sixteen to sixty-eight years (mean 41 years) with an equal sex distribution. Mortality from hemangiopericytoma of the kidney has been 50 percent, and the primary mode of therapy remains surgical.

Adult↗
PubMed1991

Development of categorical identification of native and non-native bilabial stops: infants, children and adults.

Using an infant speech identification (ISI) procedure, English language environment infants, two- and six-year-old children, and adults were tested for their identification of sounds on a native (voiced/voiceless bilabial stop) and a non-native (prevoiced/voiced bilabial stop) speech continuum. Categorical perception of the two contrasts diverged as a function of age, increasing for the native contrast and decreasing for the non-native between two and six years. In Experiment 2, subjects of the same four ages were tested for their identification of a continuum of harmonic tones varying in pitch. Comparison of the results of Experiment 1 with the essentially continuous perception of this pitch continuum supports the view that the perception of the native contrast becomes more categorical with age, while perception of the non-native contrast becomes less categorical, especially at six years. Experiment 3, in which adults were tested on the three continua with a multi-trial open set procedure, demonstrated that results with the ISI procedure in Experiments 1 and 2 are comparable to results with more traditional methods. The results of the three experiments are discussed in terms of the role of specific linguistic experience in the development of categorical speech perception.

Adult↗
PubMed1991

Effects of 12-HETE on isolated dog renal arcuate arteries.

12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) is one of the major noncyclooxygenase eicosanoids formed in vascular tissue. The vasoactive effects of the cytochrome P-450 product, 12(R)-HETE and the lipoxygenase product, 12(S)-HETE, on isolated, perfused renal arcuate arteries of the dog were investigated using videomicroscopy. R and S refer to stereoconfiguration of the hydroxy group at the twelfth position of this fatty acid structure. Cumulative doses of 12(R)-HETE produced a concentration-dependent vasoconstriction (n = 9) with a threshold dose of 10(-9) M. At a concentration of 3 x 10(-7) M, 12(R)-HETE reduced vascular diameter by 63 +/- 8 microns (from 306 +/- 17 microns), which was 37 +/- 6% of the maximal vasoconstrictor response to norepinephrine (10(-6) M). The effects of 12(R)-HETE were not altered by indomethacin (10(-6) M, n = 8). The vasoconstrictor response was associated with depolarization of vascular smooth muscle from -47 +/- 1 (15 cells) to -32 +/- 1 mV (12 cells). 12(S)-HETE was also a vasoconstrictor (n = 6), but the threshold concentration for vasoconstriction was 10(-8) M. Small renal arteries obtained from ischemic-injured, but not normal, kidneys produced a metabolite when incubated with arachidonic acid, which coeluted with a 12-HETE standard using reverse-phase high-pressure liquid chromatography. The rate of synthesis of this 12-HETE-like metabolite by renal arteries obtained from ischemic-injured and normal kidneys averaged 1.2 +/- 0.4 (n = 9) and 0.1 +/- 0.1 (n = 7) pmol.h-1.mg tissue-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

Inhibitors of cytochrome P-450 attenuate the myogenic response of dog renal arcuate arteries.

The role of cytochrome P-450 in the myogenic response of isolated, perfused renal arcuate arteries of dogs to elevations in transmural pressure was examined. The phospholipase A2 inhibitor oleyloxyethylphosphorylcholine (1 and 10 microM) inhibited the greater than threefold increase in active wall tension in these arteries after an elevation in perfusion pressure from 80 to 160 mm Hg. Inhibition of cyclooxygenase activity with indomethacin (1 or 10 microM) had no effect on this response. The cytochrome P-450 inhibitors ketoconazole (10 and 100 microM) and beta-diethyl-aminoethyldiphenylpropylacetate (SKF 525A, 10 and 100 microM) also inhibited the myogenic response. At a pressure of 160 mm Hg, SKF 525A (10 microM) and ketoconazole (100 microM) reduced active wall tension in renal arteries by approximately 70%. Partial inhibition of the myogenic response was obtained after perfusion of the vessels with mechanism-based inhibitors of P-450, 1-aminobenzotriazole (75 microM) and 12-hydroxy-16-heptadecynoic acid (20 microM). The thromboxane receptor antagonist SQ 29,548 (1 or 10 microM) had no effect on the pressure-induced increase in active wall tension in renal arteries. Arachidonic acid (50 microM) constricted isolated perfused renal arteries and potentiated the myogenic response in the presence of indomethacin. This response was completely reversed by ketoconazole (100 microM) or SKF 525A (100 microM). Microsomes (1 mg/ml) prepared from small renal arteries (200-500 microns) and incubated with [1-14C]arachidonic acid (0.5 mu Ci, 50 microM) produced a metabolite that coeluted with 20-hydroxyeicosatetraenoic acid (20-HETE) during reversed-phase high-performance liquid chromatography. The formation of this product was inhibited by both ketoconazole and SKF 525A at concentrations of 10 and 100 microM. These results are consistent with the involvement of the vasoconstrictor 20-HETE and other cytochrome P-450 metabolites of endogenous fatty acids in the myogenic response.

Animals↗
PubMed1991

Apophyseal fracture of the lumbar spine in adolescence.

A case of adolescent lumbar disc herniation with apophyseal fracture is reported. The patient, a 12-year-old boy, experienced sudden onset of pain during athletic activity. Examination revealed tenderness on palpation of the L-5 and S-1 spinous processes, straightening of the lumbar spine, and exquisite pain on 10 degrees of hyperextension. Straight leg raising, Lasègue's, and bowstring tests were all positive. Magnetic resonance imaging and computed tomography confirmed the diagnosis. Treatment included exercise, ibuprofen administration, and limitation of sports activity. At 23 months, the patient is symptom-free. A literature review of 20 cases with computed tomographic or myelographic diagnosis is presented, and conservative and surgical treatment programs are outlined.

Basketball↗
PubMed1990

Cloning and expression of three rabbit kidney cDNAs encoding lauric acid omega-hydroxylases.

cDNAs encoding three cytochrome P-450 enzymes were cloned from a rabbit kidney cDNA library. These three cDNAs exhibit greater than 90% nucleotide sequence identity across the coding region. This degree of sequence identity is also seen with P450IVA4, an enzyme that catalyzes the omega-hydroxylation of prostaglandins and that is elevated during pregnancy and induced by progesterone in rabbit lung. The 3' untranslated regions of the three cDNAs display very little sequence identity, suggesting that they are the products of distinct genes. The predicted amino acid sequences derived from each cDNA and for P450IVA4 exhibit about 85% identity. Each cDNA was inserted into an expression vector for transient transfection of COS-1 cells. The transfected cells each expressed a protein recognized by antibodies to P450IVA4. Microsomes isolated from the cells transfected with each cDNA efficiently catalyzed the omega-hydroxylation of lauric acid with rates that greatly exceed that catalyzed by microsomes isolated from the host cell line. One of the cDNAs encodes an enzyme that omega-hydroxylates prostaglandin A1; however, the specific activity was 2 orders of magnitude lower than that for lauric acid. Our results indicate that the substrate selectivity of the kidney P-450s encoded by these cDNAs is distinct from that of the lung P450IVA4 and that multiple enzymes comprise P-450 class IVA in the rabbit.

Amino Acid Sequence↗
PubMed1989

Viscoelastic shoe insoles: their use in aerobic dancing.

To determine whether use of viscoelastic insoles would significantly decrease the frequency of musculoskeletal overuse injury in aerobic dancers, 139 high-level aerobic dancers were divided randomly into two groups. The control group received placebo foam insoles and test subjects were fitted with viscoelastic insoles. Subjects used these insoles during dance class for 15 weeks. Injury rates were low in both groups and no statistical difference was found. Pain syndromes were fewer in the group using viscoelastic insoles, but the difference was not statistically significant. About a third of dancers fitted with viscoelastic insoles and a tenth of placebo insert wearers found that the insoles made their shoes too tight to be comfortable. No conclusion can be drawn on whether shock-absorbing insoles decrease injuries from aerobic dancing, but use of viscoelastic insoles may improve comfort and provide pain relief for some high-level aerobic dancers if proper fit is achieved.

Adult↗
PubMed1988

Human interlimb coordination: the first 6 months of independent walking.

The organization of interlimb coordination was studied in newly walking infants with and without support and in infants who had been walking 0.5, 1, 3, and 6 months. Analysis of the temporal and distance phase relationships between the limbs revealed that newly walking infants exhibit interlimb coordination similar to that of mature walkers. The coupling between the limbs, however, is loosely constrained, approaching adult-like consistency after 3 months of walking. Providing support for the newly walking infant afforded a more consistent, mature coordination suggesting that neuromuscular development is in advance of its ability to function in the physical world.

Child Development↗
PubMed1988

Rhabdomyolysis associated with cocaine intoxication.

A case of a patient who had an acutely toxic reaction to cocaine ingestion and later developed acute renal failure secondary to rhabdomyolysis is described. Evidence of rhabdomyolysis was noted by the combination of myalgia, urine discoloration, and elevated serum concentrations of muscle enzymes. Although the mechanism of the rhabdomyolysis is unknown, the clinical presentation resembled that of a norepinephrine-induced vasoconstrictive effect that alters the metabolic demands of the muscle in such a way that the muscle is damaged.

Adult↗
PubMed1988

Irreversible opiate agonists and antagonists. IV. Analgesic actions of 14-hydroxydihydromorphinone hydrazones.

Several phenylhydrazone derivatives of oxymorphone [phenylhydrazone and p-nitrophenylhydrazone (OxyPNPH)] as well as oxymorphonazine produce a wash-resistant inhibition of radiolabeled opioid binding, suggesting nonequilibrium binding to opiate receptors. All are agonists and, in an effort to correlate their prolonged inhibition of binding with their pharmacology, we examined their analgesic actions in vivo. Dose-response curves at 1 hr revealed similar potencies of oxymorphone and the derivatives, with the exception of OxyPNPH which was significantly less potent. After 10 hr, oxymorphone at doses up to 50 mg/kg did not demonstrate any effect. In contrast, OxyPNPH at 25 mg/kg elevated tail-flick latencies from 2 to over 8 sec after 10 hr. The 50-mg/kg dose elevated latencies to approximately 5 sec after 24 hr. Oxymorphonazine and oxymorphone phenylhydrazone also produced a prolonged analgesia, although not as effectively as OxyPNPH. The prolonged analgesic actions of OxyPNPH were highly dependent upon a critical period of 2 to 3 h immediately after injection. Blockade of receptors during this period with naloxone prevented analgesia at all time points examined. If the long duration of action of OxyPNPH resulted simply from a long half-life and persistent-free compound within the brain, analgesia should have returned by 8 hr, at which time naloxone has been eliminated. The absence of analgesia 8 hr after both OxyPNPH and naloxone argues against simple pharmacokinetic mechanisms for the prolonged analgesia and is consistent with persistent receptor occupation. OxyPNPH (25 mg/kg) administered in vivo lowered radiolabeled opioid binding effectively in brain membranes despite extensive washing. OxyPNPH lowered mu1 binding by approximately 60% and mu2 binding by 35% whereas delta binding was not lowered significantly.

Analgesia↗
PubMed1987

Polyphosphate kinase from Propionibacterium shermanii. Demonstration that polyphosphates are primers and determination of the size of the synthesized polyphosphate.

Polyphosphate kinase from Propionibacterium shermanii was purified to 70% homogeneity and shown to be a monomeric enzyme of molecular weight 83,000 +/- 3,000. It was demonstrated that short chains of polyphosphate serve as primers by using [32P]polyphosphate, 6-80 residues in length for synthesis of long-chain polyphosphate glucokinase, the radiolabel was found to be at the end of the polymer, proving that the mechanism of elongation of polyphosphate by polyphosphate kinase is strictly processive. Only 1 out of 3-8 of the polyphosphate chains contained the primer, indicating that there is a second unknown pathway of initiation which does not involve the polyphosphate primer. The termination of polyphosphate synthesis was investigated. With polyphosphate as a primer, the majority of the synthesized polyphosphate was 750 residues in length. With phosphate, in place of the polyphosphate primer, the major portion was about 2,000 residues in length but there was a large span of chain lengths down to 300. Termination is influenced by pH, temperature, and the concentration of the polyphosphate primer, with the chain length decreasing as either the temperature or the concentration of primer is increased.

Adenosine Triphosphate↗
PubMed1987

Preparation of standards and determination of sizes of long-chain polyphosphates by gel electrophoresis.

Procedures are presented for isolating fractions of long-chain polyphosphates which have a narrow range of sizes and for determining their chain lengths. The polyphosphates are isolated by elution from preparative polyacrylamide gels. Then, the lengths of these polymers are determined by a method of successive approximations of length from data obtained by electrophoresis on several different gels of varying polyacrylamide concentrations. Once sized, these isolated polyphosphates may be used as electrophoresis standards, making it possible to rapidly and accurately ascertain the size of other samples having unknown chain lengths. By comparison with two other procedures for sizing polyphosphates, it is shown that the method is definitely valid to a length of 450 and most likely to a length of at least 900. This electrophoresis procedure allows, for the first time, the determination of the range of sizes present and the average chain length with only 2-20 micrograms of polyphosphate.

DNA↗
PubMed1987

The effects of videogame playing on the response selection processing of elderly adults.

Within an information processing framework, age-related declines in speeded responding are attributed to one or more stages of processing. It was the purpose of this experiment to demonstrate the potential reversibility of this decline in at least one processing stage, response selection. Two groups of elderly participants (57 to 83 years) were pretested on a two-choice reaction time (RT) task under two levels of spatial stimulus-response (S-R) compatibility, a task demand shown to affect response selection. Following the pretest, one group participated in 7 weeks of videogame play, whereas a second group did not. All participants were posttested on the same two-choice RT task. The results of the analysis of covariance revealed that those elderly individuals who played videogames were faster than the control participants under both levels of S-R compatibility. The effect of videogame play, however, was greater for low compatibility. These results are taken as support for a potential to improve response selection through videogame play.

Aged↗