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Biomedical subjects

J C Rose

Publications and source records attributed to J C Rose.

At least 91 records · Page 5Linked to original sources

Cortical bone maintenance in an historic Afro-American cemetery sample from Cedar Grove, Arkansas.

The relocation and analysis of 80 skeletons from the Cedar Grove Cemetery, located in southwest Arkansas, provides an opportunity to examine the level of health and nutrition experienced by Afro-Americans in the post-Reconstruction South (1878-1930). The demographic profile lends support to the interpretation that Cedar Grove participated in the nationwide decline in Afro-American health. The high frequencies of skeletal lesions indicative of dietary deficiencies and infectious disease demonstrate that this was a highly stressed population. For this analysis, adult femoral thin sections (15 females and 14 males) are examined histologically. These data provide support to the assertion that the Cedar Grove population experienced poor health. Measures taken from the sections include cortical thickness, percent cortical area, and mean number of resorption spaces and forming osteons per square millimeter of bone. As a group, they demonstrate low percent cortical area compared with well-nourished normals. They also show high rates of resorption to formation, thereby disrupting the balance necessary for normal cortical bone maintenance. The pattern established for bone porosity in this group is not a function of age but rather is due to other factors, most likely nutrition and disease stress. What may be unique about this group is that males, as well as females, experienced problems with calcium homeostasis and normal maintenance and repair of bone. Taken together, these data support the interpretation that diet and health were substandard in the post-Reconstruction South.

Black or African American↗

Changes in cyclic adenosine monophosphate-phosphodiesterase activity in nonpregnant and pregnant human myometrium.

Cyclic adenosine monophosphate-phosphodiesterase is the enzyme responsible for cyclic adenosine monophosphate degradation. We investigated the kinetic behavior of this enzyme in the myometrium of women who were nonpregnant, pregnant at term not in labor, and pregnant at term in active labor. Phosphodiesterase activity was measured in the 100,000 g supernatant by the two-step isotopic procedure. The Km (Michaelis constant) value remains essentially unchanged from the nonpregnant to the pregnant state and subsequent labor in both the low and the high affinity enzymes. During pregnancy the V max (maximum velocity) is 75% less than in the nonpregnant state (p less than 0.005) and remains unchanged during labor. This is true for both the high and the low affinity enzymes. These changes in the kinetic characteristics of the cyclic adenosine monophosphate-phosphodiesterase are indicative of noncompetitive inhibition. We conclude that this inhibition may be interpreted as part of the mechanism for uterine smooth muscle relaxation and pregnancy maintenance.

3',5'-Cyclic-AMP Phosphodiesterases↗

Vasopressin-induced bradycardia in fetal and adult sheep is not dependent on an increase in blood pressure.

Other investigators have reported that intravenous infusion of synthetic arginine vasopressin into fetal lambs increases mean arterial pressure and decreases heart rate. To determine if the bradycardia produced by arginine vasopressin is a reflex response to the increase in blood pressure, we studied the effect of arginine vasopressin infusion on heart rate with and without blocking the increase in blood pressure. We performed 34 experiments in 12 chronically cannulated fetal lambs between 103 and 137 days' gestation. All animals had normal blood gas and pH values. Infusion of arginine vasopressin increased mean arterial pressure 10.1 +/- 1.1 mm Hg and decreased heart rate 50 +/- 8 bpm. Fetal heart rate decreased similarly when arginine vasopressin was infused and the hypertensive response was blocked with nitroprusside or a selective vasoconstrictor antagonist. [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 2-(O-methyl)tyrosine] arginine vasopressin. For comparison we also studied five adult nonpregnant ewes. Bradycardia was observed in the adults after infusion of arginine vasopressin alone and when the hypertensive response was blocked with the vasoconstrictor antagonist. We conclude that arginine vasopressin infusion causes a fall in heart rate independent of any increase in blood pressure in both the fetal lamb and the adult sheep.

Animals↗

Human fetal breathing response to intravenous glucose is directly related to gestational age.

This prospective longitudinal study examined human fetal breathing activity over the second half of pregnancy both in the fasting state and after intravenous glucose administration. There was a linear relationship between gestational age and percent time spent breathing after glucose between 19 and 38 weeks' gestation. However, no such correlation could be demonstrated between gestational age and fetal breathing activity in the fasting state.

Embryonic and Fetal Development↗

Epidural clonidine produces antinociception, but not hypotension, in sheep.

Intrathecally administered clonidine produces analgesia, but also produces hypotension. To assess the effects of epidural administration, the authors inserted lumbar epidural catheters in seven nonpregnant ewes, and injected, on separate days, clonidine (50-750 mcg), morphine (5-10 mg), and a clonidine-morphine combination (clonidine 150 mcg + morphine 5 mg). Clonidine produced dose-dependent antinociception and sedation, with the lowest maximally effective antinociceptive dose being 300 mcg. Morphine produced less intense antinociception than clonidine, and did not potentiate clonidine's effect. Antinociception, but not sedation, following clonidine injection was reversed by epidural injection of the alpha 2-adrenergic antagonist, idazoxan. Epidurally administered naloxone and prazosin did not reverse clonidine's antinociceptive effect, nor did intravenously administered idazoxan. Epidurally administered clonidine did not decrease blood pressure or heart rate or affect arterial blood gas tensions or spinal cord histology. These data suggest that epidurally administered clonidine produces analgesia by a local, alpha 2-adrenergic mechanism. In sheep, epidurally administered clonidine does not produce hypotension.

Analgesia↗

Responses to converting-enzyme inhibition and hemorrhage in newborn lambs and adult sheep.

We compared the cardiovascular and hormonal responses to angiotensin converting enzyme inhibition and hemorrhage of 20% of blood volume in chronically instrumented unanesthetized newborn lambs and adult sheep. Administration of the nonsulfhydryl-containing converting-enzyme inhibitor enalapril reduced mean arterial pressure in the newborn but not in the adult animals. Blood pressure fell in both age groups after hemorrhage, and the hemorrhage-induced fall in blood pressure, integrated over the period of hypovolemia, was more pronounced when converting-enzyme inhibition was present in the lambs. This was not observed in the adults. Cardiac output fell following hemorrhage in both age groups, and the fall was greater when enalapril was present in the lambs, but this was not the case in the adults. Hemorrhage increased plasma renin activity in both groups, and enalapril augmented this increase. Plasma concentrations of vasopressin and catecholamines increased following hemorrhage within and between groups. Taken together these data suggest that the renin-angiotensin system plays a more important role in the maintenance of cardiovascular homeostasis in newborn lambs than it does in adult sheep, and catecholamine and vasopressin responses to volume loss can occur in the presence of blockade of the renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗

Cardiovascular and endocrine response to hemorrhage after alpha 1-blockade in lambs and ewes.

To evaluate the role of the alpha 1-adrenergic system in the response to hemorrhage during development, lambs and adult sheep were chronically catheterized and hemorrhaged after pretreatment with prazosin or vehicle. The adults became markedly more hypotensive after alpha 1-blockade and hemorrhage than after vehicle and hemorrhage (26.1 +/- 4 vs. 10.7 +/- 2%, P less than 0.0001), whereas the lambs were no more hypotensive when hemorrhaged after prazosin (21.5 +/- 3.2 vs. 23.1 +/- 4.4%, P greater than 0.05). In the adults and the lambs, hemorrhage produced elevations in plasma renin activity and arginine vasopressin. However, after prazosin, the adults had a far greater increase in arginine vasopressin levels than after vehicle treatment (1,970 +/- 820 vs. 320 +/- 273%).

Adrenergic alpha-Antagonists↗

Effects of intracellular and extracellular calcium blockers on the pulmonary vascular responses to PGF2 alpha and U46619.

In this study, TMB-8, an intracellular calcium antagonist, and verapamil, an extracellular calcium antagonist, were used simultaneously to elucidate the role of calcium in the pulmonary vasopressor response induced by PGF2 alpha and U46619. The pulmonary vasoconstrictor action of these two agonists was evaluated in the canine isolated lung lobe preparation. Lobar arterial pressure was constantly monitored and changes in arterial pressure were recorded as a percentage from baseline. Control responses to PGF2 alpha (42.0 +/- 8.2%) and U46619 (47.2 +/- 7.0%) were obtained prior to the administration of TMB-8 and verapamil. After administration of TMB-8 and verapamil, the PGF2 alpha (7.4 +/- 3.1%) and U46619 (28.8 +/- 6.2%) responses were significantly attenuated. We conclude that the PGF2 alpha pressor response is dependent on a TMB-8-sensitive intracellular calcium pool and a verapamil-sensitive slow-channel calcium influx. In contrast, the degree of attenuation of the U46619 response was similar to the vasopressor response in the presence of verapamil alone, as described previously. This indicates a direct dependence on extracellular calcium. An additional source of calcium insensitive to verapamil and TMB-8 may also be activated and contribute to the pulmonary vasoconstrictor action. These results suggest that each agonist possesses a mechanism of action distinctly different from the other.

Animals↗

UNRWA and the health of Palestinian refugees. United Nations Relief and Works Agency.

The United Nations Relief and Works Agency for Palestine refugees (UNRWA) has provided health, education, and welfare services since 1949. A team of physicians from Georgetown University visited UNRWA Health Centers and refugee camps in Jordan, Lebanon, the West Bank, and the Gaza Strip, as well as some affiliated hospitals. Living conditions of refugees vary widely. In Jordan and the West Bank, fewer than one third live in camps, whereas in the Gaza Strip and Lebanon, conditions are more crowded. Effective programs for health education, maternal and child health, and immunization have markedly improved the health of the refugees over the years of UNRWA's operation. The general health of the population is good, primarily as a result of wise emphasis on public health and preventive medicine measures.

Child↗

Temporal and receptor correlates of the estrogen response in sheep.

Uterine blood flow and uterine cytosol and nuclear estrogen receptors were measured at critical times during estradiol-induced vasodilatation in acute anesthetized and chronic conscious sheep preparations at estradiol bolus injection frequencies from 1 to 24 hours. During acute experiments, the uterine blood flow response was muted and cytosol estrogen receptor replenishment did not occur whereas full replenishment occurred in 12 hours in conscious ewes. In ewes treated with daily estradiol that had a stable daily uterine blood flow response, the uterine blood flow response 24 hours after uterine biopsy was similar to the preoperative one. Analysis of the duration of peak uterine blood flow levels and the rate of uterine blood flow descent from peak levels showed that an interval of 18 hours between estradiol injections was necessary for the uterine blood flow response to approximate that observed after 24 hours. These observations suggest: (1) that uterine vascular receptor replenishment is delayed compared with that of the total uterus; (2) that operative stress compromises cytosol estrogen receptor metabolism and possibly nuclear estrogen receptor function; (3) that the delayed maximum uterine blood flow response to estradiol in ewes previously untreated with estradiol is due to a trophic uterine effect of daily estradiol stimulation.

Animals↗

Characterization of opioid receptor binding in adult and fetal sheep brain regions.

Opioid receptor binding was studied in 3 brain regions from maternal and fetal sheep at various gestational ages. [3H]dihydromorphine [( 3H]DHM) and [3H]D-Ala2,D-Leu5-enkephalin ([3H]DADLE) were employed as radioligands to characterize mu- and delta-opioid receptor binding sites, respectively. [3H]DHM binding was found to be highest in maternal cerebellum, intermediate in frontal cortex, and lowest in hippocampus. [3H]DADLE binding was highest in frontal cortex, intermediate in hippocampus and lowest in cerebellum. Cerebellum was the only tissue studied which contained more [3H]DHM than [3H]DADLE binding sites. Dissociation constants for [3H]DHM binding were similar in all 3 brain regions from both maternal and fetal sheep, while the dissociation constant for [3H]DADLE binding was significantly higher in cerebellum than in frontal cortex or hippocampus. Binding of both mu- and delta-receptor-selective ligands was 70% of maternal values in fetal cerebellum at 97-101 days of gestation and gradually increased over the remainder of the gestational period studied. Levels of [3H]DHM binding in frontal cortex and hippocampus were also similar to maternal levels at all timepoints studied. In contrast, [3H]DADLE binding was only 40-45% of maternal levels in fetal frontal cortex and hippocampus prior to 110 days of gestation, followed by a rapid increase in binding in both brain regions.

Aging↗

Effects of halothane on the intramyocardial pressure of the canine left ventricle.

In the intact canine heart a gradient of systolic intramyocardial pressure from a minimum at the epicardial region to a maximum at the endocardial region is well established. No information is, however, available regarding the effects of various anaesthetic agents on this gradient. In the present study the effects of halothane on intramyocardial pressure recorded from subendocardial and subepicardial layers of the canine left ventricular free wall were assessed. Experiments were performed on seven anaesthetised mongrel dogs ventilated with 100% oxygen. Intramyocardial pressure was recorded simultaneously from the inner and outer regions of the myocardium using two Mikro-tip pressure transducers. Halothane concentration in the inspired gas varied from 0% to 2%. In the pentobarbital anaesthetised dog halothane does not significantly change the heart rate. With increasing concentrations of halothane in inspired gas systolic intramyocardial pressure at both endocardium and epicardium decreased significantly from control values. As the halothane concentration increased, the normal differential between systolic left ventricular pressure and endocardial intramyocardial pressure was abolished. The intramyocardial pressure gradient from endocardium to epicardium, however, persisted during systole. During diastole the pressure gradient was reversed, becoming maximum in the epicardial region and minimum in the endocardial region in both control and halothane treated animals. Over the range of 0-2% halothane concentration there was no significant effect on the diastolic intramyocardial pressure gradient. These results suggest that halothane affects the myocardial tissue pressure non-uniformly across the left ventricular free wall and therefore influence sth e transmural distribution of coronary blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

By 95 days of gestation CRF increases plasma ACTH and cortisol in ovine fetuses.

Plasma adrenocorticotropin (ACTH) and cortisol (F) responses to 15-min intravenous infusions of synthetic ovine corticotropin-releasing factor (CRF) were measured by radioimmunoassay in three groups of chronically cannulated ovine fetuses. Fetuses (n = 7) in group I were 107 +/- 2 days gestation (0.72 G) and fetuses (n = 7) in group II were 126 +/- 2 days gestation (0.86 G). Group III fetuses (n = 5) were studied at 5-day intervals during the last 2 wk of gestation. Resting fetal plasma ACTH levels were not significantly different among the three experimental groups. Infusions of CRF (50 ng X kg-1 X min-1) provided similar, significant increases in fetal plasma ACTH concentrations in the three groups. In the young fetuses (group I) the ACTH responses to 500 ng X kg-1 X min-1 infusions of CRF were greater than responses to 50 ng X kg-1 X min-1 infusions P less than 0.001. In group II both doses of CRF produced equivalent increases in ACTH that were comparable with the responses to 50 ng X kg-1 X min-1 infusions in Group I. This suggests that fetal ACTH responsiveness to large doses of CRF decreases between 0.72 and 0.86 G. Resting fetal plasma F levels increased during gestation (P less than 0.01). There was an F response (P less than 0.001) to CRF in all groups with greater responses observed in the older fetuses. This suggests that fetal adrenal responsiveness to ACTH or other peptides released by CRF increases during gestation.

Adrenocorticotropic Hormone↗

Regional release of cyclooxygenase products after radiation exposure of the rat.

The present study evaluated the regional release of cyclooxygenase products 4 h following 20 Gy gamma irradiation. Thoracic shielding reduced the radiation-induced increase in immunoreactive thromboxane B2 (iTxB2) excretion to control levels while abdominal shielding partially attenuated the altered excretion of this cyclooxygenase product. To assess the role the kidneys play in the radiation-induced increase in iTxB2 excretion, an in situ isolated perfused rat kidney model was developed. The excretion rate of iTxB2 from irradiated isolated perfused kidneys was not significantly different from sham-irradiated perfused kidneys. Radiation exposure did alter renal cyclooxygenase product release in that the excretion of immunoreactive prostaglandin E2 (iPG2) and immunoreactive 6-keto-PGF1 alpha was significantly increased (P less than 0.05) in irradiated isolated perfused kidneys. These data show that radiation-induced increases in iTxB2 excretion are primarily due to altered extrarenal synthesis and/or metabolism of this arachidonate metabolite.

6-Ketoprostaglandin F1 alpha↗

Fetal plasma insulin and thyroid hormone levels during acute in utero ethanol exposure in a maternal-fetal sheep model.

The effects of acute in utero ethanol (ETOH) treatment on basal and stimulated thyroid and insulin levels in fetal plasma were studied in chronically cannulated fetal sheep. In test situations, pregnant ewes (0.78-0.88 gestation) which were chronically cannulated received 2 g/kg ETOH [25% (vol/vol) in isotonic saline] for 2 h; this was followed by a maintenance iv infusion of 0.13 g/kg ETOH. Control animals received isovolemic infusions of isotonic saline. Fetal arterial plasma samples were obtained after the 2-h infusion, and basal levels of T3, T4, glucose, and insulin were measured. The 2-h ETOH infusion did not influence fetal basal plasma T3, T4, insulin, or glucose. Fetal thyroid responses to an intraarterial injection of 0.01, 0.10, 1.00, or 10.00 micrograms/kg TRH or of 5 mU/kg TSH through the fetal catheters were studied in the presence or absence of high plasma ETOH concentrations. Fetal T4 or T3 levels during the 4 h following any of these stimuli were not significantly different in ethanol-treated and control animals. The effects of acute ETOH exposure on insulin responses to a glucose challenge were studied in six chronically cannulated ewes and their fetuses using a cross-over experimental design. After the 2-h ETOH infusion, ewes received a bolus injection of 600 mg/kg 50% glucose, followed by a 1-h infusion of 624 mg/kg 50% glucose and 0.13 g/kg ETOH. In control situations, ewes received saline plus glucose. Acute ETOH treatment did not influence maternal or fetal plasma glucose levels at any time, but enhanced both maternal and fetal insulin responses to glucose. Total insulin release, as measured by the area under the insulin response curve, was greater during ETOH exposure in both mother (ETOH, 4740 +/- 1475 microU/ml X min; control, 2807 +/- 766 microU/ml X min; P = 0.05) and fetus (ETOH, 562 +/- 94 microU/ml X min; control, 363 +/- 46 microU/ml X min; P less than 0.05). Thus acute in utero ETOH exposure does not diminish plasma levels of either thyroid hormones or insulin, two important hormones for fetal growth and development. However, ethanol exposure enhances the insulin response to increases in blood glucose in both mother and fetus.

Animals↗