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Biomedical subjects

S Myers

Publications and source records attributed to S Myers.

At least 91 records · Page 5Linked to original sources

An efficient strategy for gene mapping using multipoint linkage analysis: exclusion of the multiple endocrine neoplasia 2A (MEN2A) locus from chromosome 13.

Members of four families in which multiple endocrine neoplasia type 2A (MEN-2A) is segregating were typed for seven DNA markers and one red cell enzyme marker on chromosome 13. Close linkage was excluded between the MEN2A locus and each marker locus tested. By means of multipoint analysis and the genetic map of chromosome 13 developed by Leppert et al., MEN2A was excluded from any position between the most proximal marker locus (D13S6) and the most distal marker locus (D13S3) and from within 12 cMorgans outside these two loci, respectively. However, the support of exclusion within an interval was diminished under the assumption of a substantially larger genetic map in females. The strategy of multipoint analysis, which excluded between 1.5 and 2.0 times more chromosome 13 than did two-point analysis, demonstrates the utility of linkage maps in mapping disease genes.

Chromosome Mapping↗

Decrease in rat striatal dopamine synthesis and metabolism in vivo by metabolically stable adenosine receptor agonists.

The administration of the stable adenosine analog (R)-N-(1-methyl-2-phenylethyl)adenosine (R-PIA) caused a dose-dependent decrease in the accumulation of striatal dihydroxyphenylalanine (DOPA) levels following DOPA decarboxylase inhibition, with the minimum effective dose being 0.2 mg/kg, i.p.; 5'-deoxy-5'-(ethylamino)-5'-oxoadenosine (NECA) at 0.5 mg/kg, i.p., was also active indicating that in vivo R-PIA and NECA were decreasing striatal dopamine (DA) synthesis. Both R-PIA and NECA also decreased striatal levels of the DA metabolite 3-methoxytyramine (3-MT), indicating a decreased release of DA which was consistent with their effects on DA synthesis. N-Cyclohexyladenosine (CHA) also decreased 3-MT levels. The S-isomer of PIA at an equipotent dose did not affect either DA synthesis or release. R-PIA (3 mg/kg, i.p.) antagonized the pargyline-induced increase in striatal 3-MT levels as did gamma-butyrolactone, further confirming a decreased release of striatal DA. The adenosine receptor antagonist 8-cyclopentyltheophylline antagonized the R-PIA induced-decrease in striatal DA synthesis, suggesting that the latter was mediated via adenosine receptors. It is concluded that the stable adenosine analogs R-PIA and NECA, at behaviorally active doses, are decreasing in vivo the rate of DA synthesis and release from rat striatal DA nerve terminals by an adenosine receptor-mediated effect.

Adenosine↗

Effect of urapidil on rat brain catecholamine synthesis.

The effects of urapidil, a clinically effective antihypertensive drug, on the in-vivo rate of synthesis of rat brain noradrenaline (NA) and dopamine (DA) was determined. A significant dose-dependent increase in dopa concentration by urapidil after dopa decarboxylase inhibition by NSD 1015 was observed in brain stem (3-30 mg kg-1 i.p.) and striatum (10-30 mg kg-1 i.p.), indicating increased NA and DA turnover, respectively, most probably a result of central blockade of brainstem alpha 1-adrenergic and striatal DA receptors. These results indicate that urapidil may possibly exert its central hypotensive action in part by a reduced influence on brain stem NA, thus reducing central sympathetic outflow.

Animals↗

Effects of antioxidants and hyperbaric oxygen in ameliorating experimental doxorubicin skin toxicity in the rat.

Doxorubicin, an antineoplastic drug, can cause severe ulceration if extravasated when iv injected. In this study, the effects of hyperbaric oxygenation (HBO) and the antioxidants butylated hydroxytoluene (BHT) and beta-carotene were tested on such ulcers using female Sprague-Dawley rats. It was found that HBO and vitamin A did not greatly ameliorate the ulcers produced by doxorubicin, but BHT prefed for 1 week before doxorubicin was injected was able to significantly reduce lesion size (P less than 0.05). Doxorubicin with HBO was a lethal combination, with an 87% mortality among the animals by the fourth week after injection. This was probably due to doxorubicin and HBO both promoting the formation of free radicals which are highly destructive to cells. BHT, when prefed (and to a lesser extent, beta-carotene), demonstrated a protective effect by lowering the death rate (P less than 0.05), probably due to their ability to scavenge free radicals. This experiment also tested more conventionally recommended treatments such as sodium bicarbonate (NaHCO3), hydrocortisone, and ice. NaHCO3 and hydrocortisone decreased lesion size although only at a significance of P less than 0.10. Ice did not aid in the healing of the doxorubicin-induced ulcers and even proved deleterious. Multiple injections of hydrocortisone or NaHCO3 appeared to deepen ulceration. Of all the treatments tested, free radical scavengers appear to most significantly reduce skin toxicity of doxorubicin.

Animals↗

A simple radial immunodiffusion method for assay of beta 2-microglobulin in serum.

In this method for clinical measurement of beta 2-microglobulin, a 10 g/L agarose gel containing anti-beta 2-microglobulin is used, with subsequent staining with Coomassie Blue. Although the method is slow (requiring 30 h), it is inexpensive, reliable, and accurate over the range of 1 to 10 mg/L, and is useful in the determination of beta 2-microglobulin in serum and cerebrospinal fluid. A modified procedure in which staining with silver is used may be sufficiently sensitive for the clinical assay of urine.

Humans↗

Factors affecting radioactive microsphere measurement of blood flow in pregnant guinea pigs.

Comparative blood flow studies were performed in pregnant guinea pigs using radioactive microspheres to test the effects of different sphere sizes on blood flow measurements and the relationship between flows obtained intraoperatively and those performed after 5 days of recovery from anesthesia and surgery. We observed that 1.5% of the cardiac output was shunted through the microcirculation of the carcass, gut, skin and endomyometrium when 15 mu microspheres were used. Intraoperative measurements of heart rate, cardiac output and placental blood flow are significantly lower than measurements made after 5 days recovery. These reductions were ameliorated with the addition of a continuous infusion of isoproterenol and the deletion of atropine from the anesthetic.

Animals↗

Rat intestinal acyl coenzyme A: cholesterol acyl transferase properties and location.

Microsomal acyl coenzyme A:cholesterol acyltransferase activity of rat intestinal mucosa was measured as the incorporation of [1-14C]oleic acid into cholesterol esters. Exogenous cholesterol and sterol carrier protein singly and together extended the time over which the reaction rate was linear. Cholesterol esterification was suppressed by 2-monooleoyl glyceryl ether a 2-monoglyceride analog and potential substrate, but was unaltered by alpha-glycerophosphate or lysolecithin. Esterifying activity was lowest in microsomes from the intestinal segment 0-15 cm distal to the pylorus and highest in microsomes from the 30- to 45-cm segment. The total and specific activities of acyl coenzyme A:cholesterol acyltransferase were highest in cells isolated from the crypt zones. The location and level of activity were unaffected by diversion of either pancreatic juice or pancreatic juice and bile from the intestinal lumen. These findings question the physiological significance of acyl coenzyme A:cholesterol acyl transferase in the regulation of the absorption of exogenous cholesterol.

Acyltransferases↗

Cholesterol absorption in rat intestine: role of cholesterol esterase and acyl coenzyme A:cholesterol acyltransferase.

Cholesterol esterase of pancreatic juice origin and acyl coenzyme A:cholesterol acyltransferase, both associated with the intestinal mucosa, are implicated in the extensive esterification of exogenous cholesterol during absorption. To assess the role of each enzyme, [4-14C]cholesterol absorption into mesenteric lymph of rats with normal mucosal levels of both esterification enzymes was compared with that of rats with normal acyl coenzyme A:cholesterol acyltransferase activity but deficient cholesterol esterase activity. The cholesterol esterase deficiency was accomplished by either surgical diversion of the pancreatic juice from the intestinal lumen or removal by specific immunoprecipitation of cholesterol esterase from the otherwise complete pancreatic juice. In the rats that were transferase-complete and esterase-deficient, cholesterol absorption into lymph and esterase activity in the mucosa were decreased an average of 83% and 75%, respectively, compared with rats complete with both esterification enzymes. Of the absorbed [4-14C]cholesterol in all rats, 82-90% was esterified and the mucosal levels of cholesterol esterase, even in the esterase-deficient rats, could readily account for this esterification. Because transferase activity was normal in rat intestine in which cholesterol esterase was deficient and cholesterol absorption was inhibited, transferase alone does not support the absorption of exogenous cholesterol in the absence of esterase. These results reconfirm the importance of esterification in the absorption of exogenous cholesterol and demonstrate that cholesterol esterase plays an essential role in the regulation of the absorption process.

Acyltransferases↗

Combined doppler and phased-array echocardiographic estimation of cardiac output.

The capability of a pulsed Doppler flowmeter combined with a phased-array imaging system to measure volume flow was tested in vitro and in patients undergoing cardiac catheterization. The Doppler-phased-array system (DPA) was used to determine vessel diameter and a superimposed cursor was used to locate the range and angle of the Doppler sample volume. DPA estimates of continuous flow through tubing in a water tank correlated strongly (r = 0.99) with measured flow corresponding to physiologic ranges from 3-12 l/min. For pulsatile flow in a water tank, a correlation of r = 0.86 with measured flow was obtained, whereas DPA estimates of cardiac outputs compared with Fick estimates in the 11 patients produced a correlation of r = 0.83. These data indicate that estimates of cardiac output are possible using the DPA approach.

Adult↗

Contrast M-mode ultrasonography of the inferior vena cava.

Contrast M-mode and two-dimensional ultrasonography of the inferior vena cava were performed in 65 patients with various acquired and congenital cardiac disorders. After saline was injected into a peripheral arm vein, the inferior vena cava was visualized by both methods in 60 patients (92%). The M-mode approach was better for correlating the appearance of contrast within the inferior vena cava with the ECG. This precise correlation served as the basis for differentiating patients with tricuspid insufficiency (visualization of contrast after the QRS) from those with impaired right ventricular filling (visualization of contrast before the QRS) or arrhythmia. Results with the M-mode approach suggest that conditions other than tricuspid insufficiency may cause the appearance of contrast within the inferior vena cava. M-mode echocardiography should be used to further investigate patients with impaired right ventricular filling.

Arrhythmias, Cardiac↗

Diastolic vibration of the interventricular septum in aortic insufficiency.

The echocardiograms of 46 patients with aortic insufficiency which manifested typical high frequency vibrations of the anterior mitral valve leaflet were reviewed. All patients had overt clinical evidence of aortic insufficiency which was confirmed by angiography in 17 cases. In 17 cases (eight of whom underwent catheterization and angiography), high frequency diastolic vibrations of the interventricular septum of similar frequency to those on the anterior mitral leaflet were observed. This finding was not seen in 100 control echocardiograms from patients without clinical evidence of aortic insufficiency, and represents a previously undescribed echocardiographic manifestation of this lesion.

Adolescent↗