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Biomedical subjects

E Mills

Publications and source records attributed to E Mills.

At least 19 recordsLinked to original sources

Influence of postnatal maternal stress on blood pressure and heart rate of juvenile and adult rat offspring.

UNLABELLED: Autonomic control of blood pressure (BP) and heart rate (HR) was tested in offspring of rat dams that were unmanipulated (controls) or exposed repeatedly to either (1) Postnatal restraint, (2) Postnatal s.c. injections of alkaline saline, or (3) Prenatal s.c. alkaline saline. Under urethane anesthesia, BP was higher than control in 20-day-old offspring of restrained dams and lower at 80 days. The magnitude of the BP response to autonomic ganglionic blockade (chlorisondamine) changed in parallel; the control HR accelerator response was reversed at 20 days and enhanced at 80 days. Postnatal maternal injections increased BP in 20-day-old offspring and lowered it at 80 days. The BP response to blockade was unchanged; HR acceleration was attenuated at 20 days and increased at 80 days. No influence of Prenatal maternal injections was seen in adult offspring. CONCLUSION: Post--not prenatal maternal stress disrupts BP and HR control in rat offspring; disruption is greater after restraint than injection. There is sympathetic hyperactivity in preweanlings and hypoactivity in adults.

Animals

Central serotonergic mechanisms in cardiovascular regulation.

This paper reviews the role of central serotonin-containing neurons in the control of blood pressure. Central serotonin nerves have their cell bodies in the brainstem in a number of discrete collections, from where they ascend to ramify throughout the brain, descend to terminate in the spinal cord, or send shorter projections terminating in medulla, pons, and midbrain. Activation of one important ascending serotonin pathway innervating the preoptic region of the hypothalamus causes an increase in blood pressure. Activation of a bulbospinal serotonin projection descending from the ventrolateral medulla (the B3 cell group) to terminate in the intermediolateral cell column (IML) also evokes a pressor response. This pressor response is independent of that elicited by stimulation of the ventrolateral medulla in the adjacent but separate area containing the C1 adrenaline cell group. The pressor action appears to depend on increased release of serotonin, as detected by microdialysis in the area of the IML, and to be mediated by serotonin receptors of the 5HT1 subclass, probably located on sympathetic preganglionic neurons. It is possible that neuroactive excitatory amino acids, such as glutamate or aspartate, and neuropeptides such as substance P, also play a part in the pressor response evoked by stimulation of the ventrolateral medulla in the area of the lateral B3 serotonin cells. This descending serotonin pathway also appears important in mediating the hypotensive action of the antihypertensive drugs methyldopa and clonidine.

Animals

Prenatal nicotine exposure impairs beta-adrenergic function: persistent chronotropic subsensitivity despite recovery from deficits in receptor binding.

Gestational exposure to nicotine has been shown to interfere with biochemical markers of development of central and peripheral noradrenergic activity. The current study examines the development and function of cardiac beta-adrenergic receptors in the offspring of pregnant rats given nicotine infusions of 6 mg/kg/day from gestational days 4 through 20, administered by subcutaneously implanted osmotic minipumps. Prenatal nicotine exposure delayed the development of beta-adrenergic receptor binding capabilities, as assessed with [125I]pindolol in membrane preparations from heart and kidney. The deficits in receptor binding were associated with marked subsensitivity of chronotropic responses to administration of a beta-adrenergic agonist, isoproterenol. Although the effects on receptor binding resolved after weaning, functional deficiencies in responsiveness to isoproterenol or to preganglionic electrical stimulation of sympathetic nerves to the heart persisted into adulthood. These results indicate that prenatal exposure to nicotine produces long-term alterations in adrenergic responsiveness of sympathetic target tissues.

Aging

Effect of intrathecal amino acid receptor antagonists on basal blood pressure and pressor responses to brainstem stimulation in normotensive and hypertensive rats.

The importance of spinal cord amino acid receptors in the regulation of blood pressure was investigated in normotensive (Wistar Kyoto, WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive (SPR) rats. Also investigated was the possible role of these spinal cord receptors in mediating pressor changes evoked by electrical stimulation of two separate areas of the rostral ventrolateral medulla (RVLM) containing different neuronal populations, either the adrenaline-containing C1 area or the serotonin-containing B3 area. Intrathecal administration of the amino acid receptor antagonist kynurenate (KYN), or the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2APV), reduced basal blood pressure in anesthetized SHR and SPR in a dose-dependent manner, but were ineffective or elicited only small decreases in WKY. In all three strains, electrical stimulation in RVLM, in either the C1 or B3 area, evoked frequency-dependent pressor responses. Administration of 2APV or KYN was effective in attenuating these pressor responses in all three strains of rats. The effects of stimulation in the RVLM-B3 area were virtually abolished by administration of 2APV followed by the serotonin receptor antagonist methysergide. The results suggest that spinal cord excitatory amino acid receptors are important in blood pressure regulation in rats. Amino acid receptors, perhaps of the NMDA subtype, appeared to mediate pressor responses to stimulation of the RVLM-C1 and RVLM-B3 regions in both normotensive and hypertensive animals. On the other hand, excitatory amino acid receptor antagonists reduced basal blood pressure only in the hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate

Evaluation of selective liver denervation methods.

This study compares four methods of hepatic denervation and defines the rate and physiological significance of reinnervation. Five groups of rats were prepared: 10 underwent orthotopic liver transplantation. In nine rats a 90% aqueous phenol solution was applied circumferentially to the portal vein. Thirteen rats underwent microsurgical denervation; 28 received different doses of 6-hydroxydopamine (6-HODA) administered as a single intraportal injection [50 (n = 10), 75 (n = 6), and 100 mg/kg (n = 6)]. Twelve rats were studied as controls. Rats were killed 1, 4, and 8 wk after surgery to determine liver tissue content of norepinephrine (NE). Changes in mean arterial pressure (MAP) in response to hepatic nerve stimulation, which was supramaximum in intensity and frequency, were measured before rats were killed. NE content in controls ranged from 121 to 204 ng/g and MAP increased by 30-38 mmHg after electrical stimulation. At 1, 4, and 8 wk after treatment the liver NE content was less than 1, 2.3, and 20.2 ng/g in the transplant group; less than 1, 2.7, 4.1 ng/g in the phenol group; and 17.2, less than 1, and 3 ng/g in the surgically denervated group. In the 6-HODA group, values were 18.9, 47, and 61.5 ng/g (50 mg/kg); 5.7, 20.2, and 15 ng/g (75 mg/kg); and 7.7, 2.5, and 17.5 ng/g (100 mg/kg). When the level of NE was undetectable, MAP increase after stimulation was 0-18% that of controls. When NE content was 15-23% of normal, MAP increased 49-62% regardless of the denervation technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Cerebral venous oxygen content as a measure of brain energy metabolism with increased intracranial pressure and hyperventilation.

In order to test the hypothesis that the cerebral arteriovenous oxygen difference (AVDO2) and venous oxygen content (VO2) could be used to monitor brain energy metabolism in the setting of increased intracranial pressure (ICP). 12 cats were studied with 31P-magnetic resonance spectroscopy. six cats were subjected to intracranial hypertension by cisternal infusion of saline. Energy failure occurred at an average AVDO2 of 8.4 +/- 3.2 vol% (+/- standard deviation) (range 4.7 to 14.7 vol%). The VO2 at the point of metabolic failure averaged 1.45 +/- 0.6 vol% and extended over a narrower range (1.0 to 2.9 vol%). In an additional six cats, ICP was raised to the threshold of metabolic failure and hyperventilation was then instituted (pCO2 10 to 18 torr). Five of the six cats experienced a drop in VO2 with hyperventilation. In two of these animals, hyperventilation resulted in a VO2 of 1.1 vol% or less and in metabolic failure as evidenced by a fall in phosphocreatine. It is concluded that a VO2 of less than 2 vol% is correlated with brain ischemia and that the safety of hyperventilation in the setting of increased ICP can be monitored by the use of VO2.

Animals

Development of the sympathetic nervous system response to endotoxicosis in the rat: importance of non-baroreflex mechanisms in pre-weanlings and adults.

The sympathetic nervous system response to endotoxicosis was studied in the rat at ages before (11-12 days) and after (19-20 days) maturation of the baroreflex and in adults by recording preganglionic impulses during i.v. infusions of endotoxin (S. enteriditis). At all ages, the discharge rate increased before there was any decrease in arterial blood pressure. The magnitude of the increase (65%) was the same in 11-12 days-old and adult rats while 19-20 days-old rats were hyperactive (278% increase). Subsequently, in the hypotensive phase of the endotoxicosis (diastolic pressure decrease 50-60%) there was an additional increase in discharge in the 19-20 days- old rats (43% and in adults (70%) but not in 11-12 days-old rats. The hypotensive discharge rate of the 11-12 days-old rat reached only 20% of the maximum; it reached 80% in the hyperactive 19-20 days-old rat and 65% in adults. At all ages, the elevated hypotensive discharge rate persisted after steady state blood pressure was raised by infusing dextran. The discharge rate was diminished transiently during pressor responses to accelerated infusion or bolus injections of dextran. The conclusions are: (i) endotoxic stimulation of sympathetic outflow is initiated by a non-baroreflex mechanism in adult as well as in pre-weaning rats; (ii) there is added stimulation during hypotension after the baroreflex is mature, but (iii) the non-baroreflex stimulation continues to excite the preganglionic neurons and obtunds baroreflex feedback inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Vectors, promoters, and expression of genes in chick embryos.

Transgenic chickens were produced by injecting the Day-1 egg with 10(5) infectious particles of a replication-competent virus based on the Schmidt-Ruppin A strain of Rous sarcoma virus. The chickens were resistant to transforming subgroup A virus containing the src gene but not the corresponding subgroup B virus. Transgenic chickens producing bovine growth hormone (bGH) were generated using a modified virus containing the Bryan high titre polymerase gene. The virus was constructed with the bGH gene and the mouse metallothionein promoter in the reverse orientation relative to the viral structural genes. Two male chickens produced serum concentrations of approximately 100 ng bGH/ml; the birds were larger than controls and matured more rapidly. Transgenic mice required for the analysis of skeletal muscle-specific expression in vivo were produced using 5'-flanking regions of the chicken alpha-skeletal actin promoter linked to a luciferase reporter gene to determine the region essential for tissue-specific expression. The defined promoter sequences are to be used in experiments designed to direct expression of growth-promoting genes in skeletal muscle of chickens.

Animals

Malignant fibrous histiocytoma (malignant fibrous xanthoma: xanthosarcoma) of bone.

Seven cases of malignant fibrous histiocytoma of bone are documented. In addition to typical histologic features such as the presence of a storiform pattern, histiocytic and fibrocytic cell types and severe cellular atypism, in five cases there were areas in which osteoclast-type giant cells were prominent and the lesion resembled a giant cell tumor. Three of the seven patients developed pulmonary metastases within two years of amputation, one developed extensive local recurrence including soft tissue and vascular invasion, and the other three are without evidence of disease but have been followed for only short periods.

Adolescent

Central depression of carotid baroreceptor pressor response, arterial pressure and heart rate by 5-hydroxytryptophan: influence of supracollicular areas of the brain.

5-Hydroxytryptophan (5-htp) administered into the fourth cerebral ventricle of cats decreased resting arterial blood pressure, preganglionic sympathetic nerve activity and heart rate in both intact brain and midcollicular decerebrate preparations. The increases in sympathetic nerve discharge and blood pressure in response to bilateral carotid occlusion were reduced after 5-HTP administration when the brain was intact but not in midcollicular decerebrate preparations. Resting arterial pressure, heart rate and bilateral carotid occlusion response were not affected when the distribution of 5-HTP was confined to neural structures rostral to the midcollicular level by injection into the third or lateral cerebral ventricle with the cerebral aqueduct cannulated for drainage. Prior intracerebroventricular administration of an L-amino acid decarboxylase inhibitor (Ro 4-4602) prevented the effects of 5-HTP, indicating that depression is mediated via conversion to serotonin. These results suggest that serotenergic stimulation in the caudal brainstem or spinal cord produces depression of sympathetic outflow and decreases arterial blood pressure and heart rate. The bilateral carotid occlusion response is depressed by the brainstem serotonergic mechanisms which require the integrity of neural pathways connecting sub- and supracollicular areas of the brain. The possibility of reciprocal influence by the central serotonergic and adrenergic systems in cardiovascular control is discussed.

5-Hydroxytryptophan

Nurse clinician productivity using a relative value scale.

The use of relative value units to measure the productivity of nurse clinicians in four primary care practices is described. Relative value points and equivalent dollar values assigned to services provided by professionals yielded a different assessment of productivity than that provided by a count of patient visits. The physician-nurse clinician teams studied were only 6 percent more productive than the physician-nurse teams when productivity was measured by the number of patient visits processed during an 8-hour period but were 26 percent more productive in terms of the value of services they produced per day.

Efficiency