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Biomedical subjects

W R Hiatt

Publications and source records attributed to W R Hiatt.

At least 109 records · Page 6Linked to original sources
PubMed1988

Reduction of polygalacturonase activity in tomato fruit by antisense RNA.

Polygalacturonase [PG; poly(1,4-alpha-D-galacturonide) glycanhydrolase; EC 3.2.1.15] is expressed in tomato only during the ripening stage of fruit development. PG becomes abundant during ripening and has a major role in cell wall degradation and fruit softening. Tomato plants were transformed to produce antisense RNA from a gene construct containing the cauliflower mosaic virus 35S promoter and a full-length PG cDNA in reverse orientation. The construct was integrated into the tomato genome by Agrobacterium-mediated transformation. The constitutive synthesis of PG antisense RNA in transgenic plants resulted in a substantial reduction in the levels of PG mRNA and enzymatic activity in ripening fruit. The steady-state levels of PG antisense RNA in green fruit of transgenic plants were lower than the levels of PG mRNA normally attained during ripening. However, analysis of transcription in isolated nuclei demonstrated that the antisense RNA construct was transcribed at a higher rate than the tomato PG gene(s). Analysis of fruit from transgenic plants demonstrated a reduction in PG mRNA and enzymatic activity of 70-90%. The reduction in PG activity did not prevent the accumulation of the red pigment lycopene.

Journal Article↗
PubMed1987

Preformed hydroxylapatite blocks for palatal grafting in orthognathic surgery.

Hydroxylapatite has been used as a bone substitute for ridge augmentation, ridge maintenance and periodontal defects for many years. This is a preliminary report of the use of hydroxylapatite blocks as a grafting material in midpalatal splits in orthognathic surgery. With the advent of hydroxylapatite blocks, the need for autogenous bone grafting will, in most cases, be obviated.

Durapatite↗
PubMed1987

The balance between vascular alpha- and beta-adrenoceptors is not changed in the elderly.

It has been suggested that beta-adrenoceptor-mediated functions are diminished with aging and that these responses are reduced to a greater extent than are alpha-adrenoceptor-mediated responses. The resulting imbalance in the elderly may produce an increased vascular resistance from the unopposed alpha-adrenoceptor stimulation in the peripheral vasculature. To evaluate this hypothesis, we studied 12 healthy elderly and 12 healthy young subjects during a graded infusion of epinephrine and compared blood pressure response, vascular resistance, and calf blood flow as determined by venous occlusion plethysmography. In both groups, heart rate increased, blood flow to the leg increased, and vascular resistance fell in response to epinephrine infusion, but in the elderly the systolic blood pressure failed to rise as it did in the young subjects. From these data we conclude that the overall vascular response to epinephrine does not change with age and that the balance between beta-adrenoceptor-mediated vasodilation and alpha-adrenoceptor-mediated vasoconstriction is therefore unchanged in the elderly.

Adult↗
PubMed1987

Carnitine metabolism during exercise in patients with peripheral vascular disease.

The distribution between carnitine and the acyl derivatives of carnitine reflects changes in the metabolic state of a variety of tissues. Patients with peripheral vascular disease (PVD) develop skeletal muscle ischemia with exertion. This impairment in oxidative metabolism during exercise may result in the generation of acylcarnitines. To test this hypothesis, 11 patients with PVD and 7 age-matched control subjects were evaluated with graded treadmill exercise. Subjects with PVD walked to maximal claudication pain at a peak O2 consumption (VO2) of 19.9 +/- 1.3 ml X kg-1 X min-1 (mean +/- SE). Control subjects were taken to a near-maximal work load at a VO2 of 31.3 +/- 1.0 ml X kg-1 X min-1. In patients with PVD, the plasma concentration of total acid-soluble, long-chain acylcarnitine and total carnitine was increased at peak exercise compared with resting values. Four minutes postexercise, the plasma short-chain acylcarnitine concentration was also increased. In control subjects taken to the higher work load, only the long-chain acylcarnitine concentration was increased at peak exercise. In patients with PVD, plasma short-chain acylcarnitine concentration at rest was negatively correlated with subsequent maximal walking time (r = -0.51, P less than 0.05). In conclusion, acylcarnitines increased in patients with PVD who walked to maximal claudication pain, whereas control subjects did not show equivalent changes even when taken to a higher work load. The relationship between short-chain acylcarnitine concentration at rest and subsequent exercise performance suggests that repeated episodes of ischemia may cause chronic accumulation of short-chain acylcarnitine in plasma in proportion to the severity of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1987

Multiple oral petechiae and ecchymoses in a patient with osteoarthritis.

Ibuprofen is a frequently used medication, and possible drug reactions should be familiar to the clinician. Because oral manifestations of thrombocytopenia are often the initial finding and possibly represent the only clinical evidence of this disease, the dentist should be able to recognize the significance of these lesions and refer the patient for appropriate evaluation and therapy.

Aged↗
PubMed1986

Use of preformed hydroxylapatite blocks for grafting in genioplasty procedures.

Dense hydroxylapatite is a synthetic, biocompatible, immunologically inert material that can establish a chemical union with bone when placed in intimate contact in histologic studies. The following is a preliminary report of the use of preformed dense, non-resorbable hydroxylapatite blocks as a grafting material for use in advancement and vertical lengthening of the bony chin associated with orthognathic surgical procedures. In rare instances where an autogenous bone graft would be required for vertical lengthening without any advancement of bony pogonion, the need is obviated by utilization of the hydroxylapatite solid block.

Chin↗
PubMed1986

Identification of epsilon-N-mono-, epsilon-N-di-, and epsilon-N-trimethyllysine by high-performance liquid chromatography.

Dansyl derivatives of epsilon-N-mono-, epsilon-N-di-, and epsilon-N-trimethyllysine were resolved from other amino acids in proteins by the use of high-performance liquid chromatography. The system was tested with amino acid standard combinations as well as with acid-hydrolyzed proteins known to contain methylated residues. In all cases the methylated lysines were well resolved.

Chromatography, High Pressure Liquid↗
PubMed1986

Effects of selective and nonselective beta-adrenergic blockade on mechanisms of exercise conditioning.

Exercise conditioning involves adaptations in the heart, peripheral circulation, and trained skeletal muscle that result in improved exercise capacity. Since the specific influence of beta-adrenergic stimulation on these various adaptations has not been clear, we studied the effect of beta 1-selective and nonselective beta-adrenergic blockade on the exercise conditioning response of 24 healthy, sedentary men after an intensive 6 week aerobic training program. Subjects randomly assigned to receive placebo, 50 mg bid atenolol, or 40 mg bid nadolol were tested before and after training both on and off drugs. Comparable reductions in maximal exercise heart rate occurred with atenolol and nadolol, indicating equivalent beta 1-adrenergic blockade. Vascular beta 2-adrenergic selectivity was maintained with atenolol as determined by calf plethysmography during intravenous infusion of epinephrine. All subjects trained at greater than 85% of maximal heart rate and 80% of VO2 max determined on drug. VO2 max increased after training 16 +/- 2% (p less than .05) in the placebo group and 6 +/- 2% (p less than .05) in the atenolol group, while there was no change in the nadolol group. At maximal exercise, subjects receiving placebo increased their exercise duration and oxygen pulse significantly greater than those receiving atenolol or nadolol. During submaximal exercise there were reductions in heart rate and heart rate-blood pressure product in all three groups, but these reductions were greater with placebo than with either drug. Leg blood flow during submaximal exercise decreased 24 +/- 2% (p less than .01) in the placebo group but was unchanged in the atenolol and nadolol groups. Lactates in arterialized blood during submaximal exercise were reduced equivalently in all three groups after training. Capillary/fiber ratio in vastus lateralis muscle biopsy specimens increased 31 +/- 6% in the placebo group and 21 +/- 6% in the atenolol group (both p less than .05) and tended to increase in the nadolol group. Succinic dehydrogenase and cytochrome oxidase activities in muscle biopsy specimens increased equivalently in all three groups, especially during submaximal exercise, these changes were less marked than that with placebo. While beta-adrenergic blockade attenuated the exercise conditioning response, skeletal muscle adaptations including increases in oxidative enzymes, capillary supply, and decreases in exercise blood lactates were unaffected. Cardiac and peripheral vascular adaptations do appear to be affected by beta-adrenergic blockade during training. Cardioselectivity does not seem to be important in modifying these effects.

Adrenergic beta-Antagonists↗
PubMed1985

A single amino acid substitution in the enzyme 5-enolpyruvylshikimate-3-phosphate synthase confers resistance to the herbicide glyphosate.

The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EC 2.5.1.19), encoded by the aroA locus, is a target site of glyphosate inhibition in bacteria. A glyphosate-resistant aroA allele has been cloned in Escherichia coli from a mutagenized strain of Salmonella typhimurium. Subcloning of this mutant aroA allele shows the gene to reside on a 1.3-kilobase segment of S. typhimurium DNA. Nucleotide sequence analysis of this mutant gene indicates a protein-coding region 427 amino acids in length. Comparison of the mutant and wild type aroA gene sequences reveals a single base pair change resulting in a Pro to Ser amino acid substitution at the 101st codon of the protein. A hybrid gene fusion between mutant and wild type aroA gene sequences was constructed. 5-Enolpyruvylshikimate-3-phosphate synthase was prepared from E. coli cells harboring this construct. The glyphosate-resistant phenotype is shown to be associated with the single amino acid substitution described above.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1985

beta-2 Adrenergic blockade evaluated with epinephrine after placebo, atenolol, and nadolol.

Vascular beta 2-adrenergic blocking effects of the water-soluble drugs atenolol (beta 1-selective) and nadolol (nonselective) were evaluated. Twenty-four healthy young men were studied in three dosing groups (eight subjects per group) before and after 1 wk on placebo, atenolol (50 mg twice a day), or nadolol (40 mg twice a day). Maximal treadmill exercise heart rates were reduced to a similar degree by atenolol (-48 +/- 3 bpm) and nadolol (-48 +/- 4 bpm) but were not affected by placebo. Trough blood levels were 226 +/- 9 ng/ml for atenolol and 43 +/- 9 ng/ml for nadolol. Calf blood flow was measured with a plethysmograph and calf vascular resistance was calculated from blood pressure and flow. beta 2-Adrenergic blockade was determined at rest with epinephrine infused intravenously in graded doses from 0.001 to 0.032 micrograms/kg/min. Mean arterial pressure and calf vascular resistance rose markedly after nadolol but not after atenolol or placebo. Marked bradycardia developed after nadolol, probably by baroreceptor stimulation. Thus at an equivalent, substantial degree of beta 1-adrenergic blockade, nadolol blocks vascular beta 2-adrenergic receptors and atenolol does not. Measurement of the peripheral vascular response to epinephrine infusion is an effective means of assessing the impact of beta-adrenergic blockers on vascular beta 2-adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed1985

Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease.

Beta-Adrenergic blockers have not been widely used in patients with peripheral vascular disease because these drugs have been reported to worsen the symptoms of intermittent claudication. To test this assumption we studied the effects of a beta 1-selective and a nonselective beta-adrenergic blocker on postexercise calf blood flow and symptoms of claudication in 19 patients with mild-to-moderate peripheral vascular disease. Subjects received placebo for 3 weeks, and then were randomized to 120 mg/day propranolol or 150 mg/day metoprolol with the use of a crossover design. Blood flow in the calf was measured by strain-gauge plethysmography at rest and immediately after exercise on a bicycle ergometer at a low and a high workload. The symptoms of claudication were monitored during bicycle exercise and by patient diaries maintained between visits. Maximal exercise heart rate was reduced an equivalent amount by metoprolol (19 beats/min) and propranolol (16 beats/min). Mean arterial pressure was reduced by propranolol at rest and by both drugs with exercise. Calf blood flow was not affected by either drug compared with placebo at rest or at either workload. In addition, the symptoms of claudication were not worsened by either drug. We conclude that despite evidence of beta 1-adrenergic blockade and a lowering of arterial pressure, neither beta-adrenergic blocker adversely affected the peripheral circulation.

Adrenergic beta-Antagonists↗
PubMed1985

The effect of platelet protein and DNA on the measurement of human lymphocyte beta adrenergic receptor number.

Considerable variation exists in human lymphocyte beta adrenergic receptor measurements when the data are reported as fmole/mg protein. To investigate potential sources of measurement errors, human lymphocytes were prepared as follows: With the standard method (M1), lymphocytes were removed from heparinized whole blood by centrifugation on a ficoll gradient. The modified method (M2) was identical, except for an initial centrifugation to remove platelet-rich plasma. Beta adrenergic receptors were measured by the binding of [125I] pindolol with the results analyzed by the method of Scatchard. The M1 receptor number was 11.9 +/- 1.8 fmole/mg protein compared to 26.7 +/- 4.1 fmole/mg for M2 (p1/40.01). Since platelet-rich M1 had 71.9 micrograms protein/100 microL of sample and platelet-poor M2 and 23.8 micrograms/100 microL the difference in receptor number is a calculation artifact due to platelet protein. Similar results were obtained when data were expressed as fmole/mg DNA, because platelets also contain nucleic acids. However, when expressed as the number of binding sites/cell, neither platelet protein nor platelet-DNA affected receptor quantitation. We conclude that results are most accurately reported as sites/cell.

Adult↗
PubMed1984

Effect of aerobic conditioning on the peripheral circulation during chronic beta-adrenergic blockade.

The relation of peripheral circulatory adjustments to exercise training during long-term beta-adrenergic blockade has not been investigated. In 12 healthy men aged 22 to 34 years, blood flow in the calf was evaluated with submaximal exercise before and after a 6 week aerobic conditioning program. During conditioning, six subjects received no drug and six received propranolol, 80 to 120 mg/day in divided doses. Treated and control subjects were studied on entry and at the conclusion of a conditioning program, 72 hours after drug withdrawal in subjects given propranolol. The training was intensive and equivalent in both groups. Control subjects increased maximal oxygen uptake from 47.5 +/- 1.1 to 51.4 +/- 0.4 ml/kg per min (p less than 0.05), whereas those on propranolol did not improve. Immediately after exercise, blood flow in the calf was measured with strain gauge plethysmography after 3 minutes of supine exertion on a cycle ergometer. In control subjects, flow decreased from 15.7 +/- 1.6 to 14.0 +/- 1.4 ml/100 ml per min at 300 kg-m/min of exertion (p less than 0.05) and from 26.5 +/- 3.8 to 21.8 +/- 2.3 ml/100 ml per min at 700 kg-m/min (p less than 0.05). Vascular resistance was unchanged in these subjects at 300 kg-m/min (6.1 +/- 0.8 to 6.7 +/- 1.0 pru) (p = NS), but increased at 700 kg-m/min (4.2 +/- 0.8 to 4.8 +/- 0.7 pru) (p less than 0.05). In subjects given propranolol, no change in flow or resistance occurred after training at either work load.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Selective and nonselective beta-blockade of the peripheral circulation.

The effects of selective beta 1- as compared to nonselective beta-adrenergic blocking drugs on the peripheral circulation have not been adequately investigated. Ten healthy subjects received placebo for 1 wk followed by 4 wk of either propranolol or metoprolol in equivalent but increasing doses each week. Subjects then crossed over to the other sequence of placebo and drug. Measurements of calf blood flow, mean blood pressure, and calculation of calf vascular resistance were obtained at rest, after three loads of supine exercise on a bicycle ergometer, and during isoproterenol infusion testing. At the doses chosen, both beta-adrenergic blocking drugs induced equivalent decreases in exercise heart rate. Metoprolol lowered resting and exercise mean blood pressure at most doses, whereas propranolol had less of an effect on this variable. Neither drug altered resting or exercise calf blood flow or vascular resistance. More isoproterenol was required to increase the heart rate and decrease the vascular resistance during treatment with propranolol than with metoprolol. We conclude that in normotensive subjects metoprolol is somewhat more effective than propranolol in lowering mean arterial pressure during exercise when the drugs are given at doses equivalent in effects on exercise heart rate. Neither drug has a deleterious effect on calf blood flow or vascular resistance. Despite this, a marked separation between the vascular beta 2-adrenergic-blocking effects of these drugs can be demonstrated with an isoproterenol infusion indicating beta 2-adrenergic-receptor sparing by metoprolol.

Adult↗