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Biomedical subjects

N Alexander

Publications and source records attributed to N Alexander.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of chronic sinoaortic denervation on central vasopressin and catecholamine systems.

The objective of this study was to determine whether chronic arterial baroreceptor deficit induces time-related changes in central vasopressin (AVP) and catecholamine systems. Groups of sinoaortic-denervated (SAD) and sham-operated (SO) rats were studied 1, 3, 4, 7, and 14 days after surgery. Supraoptic (SON), paraventricular (PVN) and arcuate (ARC) nuclei, median eminence (ME) region, and A1 region of medulla were obtained by micropunch from frozen brain sections and assayed for AVP, tyrosine hydroxylase (TH) activity, catecholamines, and their metabolites, dihydroxyphenylethyleneglycol (DOPEG) and 2,5-dihydroxyphenylacetic acid (DOPAC). AVP concentration in SON and PVN was increased in 1-day-SAD rats, reduced in 3- and 4-day-SAD rats, equal and above control values in 7- and 14-day-SAD rats, respectively. TH activity was increased in SON and reduced in ME and ARC of 1- and 7-day-SAD rats. In SON, DOPEG was increased, whereas in ME all catecholamines and DOPEG and DOPAC were reduced in 1-day-SAD rats. ME catecholamines returned toward control levels in 3- to 4-day-SAD rats. These studies show that the chronic absence of arterial baroreceptor input produces time-related, regionally specific central changes of vasopressin and regionally associated catecholamines.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Norfenefrine in the treatment of female stress incontinence. A double-blind controlled trial.

Forty-four consecutive patients with genuine stress incontinence were treated with norfenefrine 15-30 mg t.i.d. in a 6-week, double-blind and parallel, placebo-controlled study. Subjectively, 52% were improved and 26% became continent during norfenefrine treatment. Objectively (stress test), 30% became continent and the maximum urethral closure pressure increased 10% which was statistically significant. These results, however, were not statistically different from those of placebo treatment. Simultaneously, subjective and objective improvement was seen more often in patients given norfenefrine compared to placebo (p less than 0.1). In patients with most severe incontinence according to urodynamic criteria the effect of norfenefrine was statistically significantly better than placebo. A low incidence of side effects was observed and no differences between norfenefrine and placebo were found. It is concluded that norfenefrine may be of value in the treatment of female stress incontinence.

2-Hydroxyphenethylamine↗
PubMed1988

Baroreceptor influences on plasma atrial natriuretic peptide (ANP): sinoaortic denervation reduces basal levels and the response to an osmotic challenge.

The objective of these studies was to investigate baroreceptor/osmotic interactions by determining the effect of sinoaortic denervation (SAD) on the ANP response to a hypertonic saline challenge in conscious rats. A time course study showed that there was a rapid increase in plasma ANP in response to iv hypertonic saline. The peak effect was at 5 min, a 3-fold increase (P less than .01). Baroreceptor denervation produced significant decreases in basal ANP levels and osmotic induced release (P less than 0.01). Plasma ANP increased from 25 +/- 3.2 to 136.8 +/- 28 in the sham-operated rats and from 11.8 +/- 2.6 to 30.8 +/- 4.6 in the SAD. Plasma sodium was the same in the 2 groups, and there was no change in atrial ANP content. Blood pressure was elevated in the denervated animals; however, the pressor response to the hypertonic challenge was not different from the controls. These results suggest that the baroreceptor system may have important influences on cardiovascular/hormonal regulation.

Animals↗
PubMed1987

Thyroperoxidase, an auto-antigen with a mosaic structure made of nuclear and mitochondrial gene modules.

A lambda gt11 cDNA library was constructed from a normal human thyroid and screened with a rabbit anti-porcine thyroperoxidase antibody. A series of thyroperoxidase (TPO) clones were obtained which allowed determination of the complete primary structure of the protein. The library was also screened with serum from a patient with Hashimoto's thyroiditis, an autoimmune disease characterized by the presence in the serum of high titers of autoantibodies directed against the 'microsomal antigen' (McAg). Comparison of the cDNA sequences from TPO clones and McAg clones provides definite proof that the McAg is TPO. A short segment of TPO was characterized as bearing a major epitope involved in autoimmunity. The primary structure of TPO was 42% homologous to myeloperoxidase (MPO). It contains, in addition, a C-terminal extension with a membrane anchor region contiguous to two domains encoded by modules belonging to the EGF and C4b gene families. The existence in TPO of still another domain presenting a significant homology with a putative heme-binding region of cytochrome C oxidase polypeptide I raises the possibility that a mitochondrial gene module has contributed a piece to the evolution of a typical nuclear mosaic gene.

Amino Acid Sequence↗
PubMed1987

Suppressed serum prolactin in sinoaortic-denervated rats.

We investigated the effect of arterial baroreceptor deafferentation on serum and pituitary prolactin (PRL) and on catecholamines in median eminence (ME) and anterior and posterior pituitaries. Male Wistar rats were sinoaortic denervated (SAD) or sham operated (SO). Three days after surgery serum prolactin, measured by radioimmunoassay, was suppressed in SAD rats (-54%, P less than 0.05), and dopamine (DA) and norepinephrine (NE) concentrations, measured by radioenzymatic or high-performance liquid chromatography electron capture methods, were significantly reduced in ME of SAD rats (NE, -54% P less than 0.005 and DA, -56% P less than 0.001). Simultaneously, anterior pituitary of SAD rats had significant increases in both catecholamines, whereas posterior pituitary showed no changes. Four hours after surgery serum PRL was also reduced (-40%, P less than 0.05) in SAD rats, but no changes in ME catecholamines were found. Mean arterial pressure (MAP) and heart rate were measured before and after injection of bromocriptine (0.5 mg/kg ip) in SAD and SO rats 3 days after surgery. Bromocriptine markedly suppressed serum PRL in both groups and reduced MAP from 144 +/- 10 to 84 +/- 5 and from 116 +/- 2 to 99 +/- 3 in SAD and SO rats, respectively; heart rate was reduced in SAD rats. We conclude that the SAD rat is a model of hypertension with suppressed serum PRL and that interruption of arterial baroreceptor nerves suppresses PRL secretion probably by modulating tuberoinfundibular turnover of catecholamines.

Animals↗
PubMed1986

Sympathetic activity, lipids accumulation, and arterial wall morphology in rabbits at high altitude.

The purpose of this study was to investigate the effect of increased sympathetic nervous activity on arterial wall viability as reflected by its response to elevated plasma lipids. Our previous finding that vascular wall viability was reduced by low sympathetic nervous activity indicated that chronically enhanced sympathetic activity should have the opposite effect. In this study rabbits were divided into two groups, both of which received 1% cholesterol in the diet. One group was born and raised at high altitude to induce chronic activation of sympathetic activity, and the other was raised at sea level. Aorta of high-altitude rabbits exhibited significantly less lipid accumulation than aortas of sea-level rabbits. This difference in lipid accumulation was accompanied by elevated norepinephrine turnover and decreased sensitivity to exogenous norepinephrine of high-altitude rabbit arteries. Vascular smooth muscle cells of high-altitude rabbits demonstrated striated increased relative volume density of mitochondria and decreased nucleocytoplasmic ratio, reflecting lower mitotic rate. These results are suggestive that enhanced chronic activity of vascular sympathetic innervation protects smooth muscle from lipid accumulation and exerts a positive effect on vascular viability.

Altitude↗
PubMed1986

Increased plasma vasopressin in sinoaortic denervated rats.

The main purpose of this study was to evaluate changes in plasma arginine vasopressin (AVP) associated with arterial baroreceptor deafferentation. Food and water intake of sham-operated (SO) rats was matched to that of sinoaortic denervated (SAD) rats, and blood samples were collected from groups of SAD and SO rats 15 min, 1-4 h, 24 h and 4-7 days after operation. Plasma AVP was 2-4 times higher in SAD than SO rats at each of the times studied during the 1st week (p less than 0.001); at those times no significant differences in hematocrit, plasma sodium or osmolality were found. Three weeks after surgery, plasma AVP was similar in both groups of rats. Mean arterial pressure, measured in additional groups of rats, was approximately 35 mm Hg higher in SAD than SO rats for the first 4 postsurgical hours, remaining about 20 mm Hg higher at the later times. Administration of an AVP pressor antagonist to SAD rats caused a small (8-11%), statistically significant reduction in the elevated pressure of SAD rats during the first 4 postsurgical days. Thus, AVP contributes modestly to the elevation of arterial pressure caused mainly by neurogenic mechanisms in SAD rats during the early postoperative period. Ingestive behavior was monitored in additional SO and SAD rats. SAD rats had significantly reduced food and water intake for 5 days after surgery, however, by day 6 intake was comparable to that of SO rats. Preoperative body weight was not regained until 2 weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Calcium-regulating hormones across the menstrual cycle.

Midcycle elevations of serum PTH, calcitonin (CT), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] in women have been reported. To examine the effects of cyclic changes in ovarian steroid secretion on calcitropic hormone concentrations, we used a cytoreceptor assay for 1,25-(OH)2D and homologous RIAs for PTH and CT to measure these hormones in daily blood samples obtained from six women throughout the menstrual cycle. Significant changes in serum PTH, CT, 1,25-(OH)2D, calcium, and phosphorus concentrations during the cycle were not found; transverse means (+/- SE) were 101 +/- 3.5 pg/ml for PTH, 30.8 +/- 1.8 pg/ml for CT, and 40.1 +/- 1.7 pg/ml for 1,25-(OH)2D. In addition, CT reserve was assessed by calcium infusion (3 mg/kg, iv, in 10 min) during the early and late follicular and midluteal phases of the cycle. Although serum CT increased significantly (P less than 0.01) after calcium infusion, the mean (+/- SE) increment (23.2 +/- 2.2 pg/ml) did not significantly differ in the three phases of the cycle (early follicular, 23.8 +/- 4.0; late follicular, 23.3 +/- 3.4; midluteal, 22.5 +/- 4.1). Our data do not support previous reports of midcycle elevations in serum PTH, CT, and 1,25-(OH)2D concentrations, and we conclude that serum concentrations of the calcitropic hormones do not significantly vary during the menstrual cycle.

Adult↗
PubMed1986

Angiotensin II receptors in adrenal gland, pituitary gland and brain of sino-aortic denervated rats.

Angiotensin II (ANG II) binding sites were quantified in individual adrenal and pituitary glands and brain nuclei of sino-aortic denervated (neurogenically hypertensive) and sham-operated rats by incubation of 16-microns tissue sections with 125I-[Sar1] Ang II, autoradiography, computerized microdensitometry and comparison with 125I-standards. In the anterior pituitary, the number of ANG II binding sites (Bmax) was increased in sino-aortic denervated rats, 764 +/- 39 versus 2025 +/- 340 fmol/mg protein in sham-operated versus sino-aortic denervated. In the adrenal medulla the Bmax was decreased in sino-aortic denervated rats, 3313 +/- 71 versus 2736 +/- 181 fmol/mg protein in sham-operated versus sino-aortic denervated. There were no significant changes in adrenal zona glomerulosa ANG II binding capacity. In the nucleus of the solitary tract the Bmax was decreased, from 1422 +/- 22 fmol/mg protein in sham-operated to 370 +/- 52 fmol/mg protein in sino-aortic denervated rats. These results indicate that changes in ANG II binding occur in peripheral tissues and brain of neurogenic hypertensive rats. Our findings suggest that both peripheral and central ANG II may be associated with the pathophysiology of neurogenic hypertension.

Adrenal Glands↗
PubMed1985

Pulmonary edema and death induced by sinoaortic denervation in fastigial nucleus-lesioned rats.

When adult male rats with lesions of the cerebellar fastigial nucleus were subjected to sinoaortic denervation and instrumented for aortic pressure recording, their elevated mean arterial pressure was found to rise no higher than that of rats with sinoaortic denervation alone; however all of the doubly operated rats died or became moribund within 4 days. Pulmonary edema and gastric ulcers were frequently seen. When the order of operations was reversed, all animals survived. The possible mechanism and involvement of other brain nuclei, catecholamines and vasopressin in these pathological changes is discussed.

Animals↗
PubMed1985

Catecholamines in plasma and erythrocytes of rats with transplantable pheochromocytoma.

Accumulation of catecholamines in erythrocytes (RBC) was compared to rising plasma levels of catecholamines at weekly intervals following transplantation of pheochromocytoma (line P-259) in the New England Deaconess Hospital rat strain. Additionally changes were investigated during a 12 hour interval after tumor was established in PHEO rats. Starting 2 weeks after tumor implant, the concentrations of norepinephrine (NE) and dopamine (DA) in RBC paralleled and correlated strongly with rising levels of plasma NE and DA which were maximum by 4 weeks. Four to 6 weeks after implant, the RBC to plasma (L/P) concentration ratio of NE was 30% higher in PHEO rats than controls (p less than 0.05) indicating a shift in distribution of NE between the 2 circulating pools. Three measurements, 6 hours apart, showed that mean arterial pressure, plasma and RBC NE and DA concentrations were highest in AM in both PHEO and control groups. Shifts in DA were smaller and did not rise in PM as did NE suggesting DA may reflect tumor secretion and NE, tumor secretion plus sympathetic neuronal activity.

Adrenal Gland Neoplasms↗
PubMed1985

Antibodies to spermatozoa and seminal plasma antigens detected by various enzyme-linked immunosorbent (ELISA) assays.

Various ELISA methods have been applied by different research centers to test the efficiency of this approach for the diagnosis of sperm-immune infertility cases. The antigens used were either whole spermatozoa or solubilized spermatozoal membrane preparations and were immobilized on microtiter plates, except in one case where plastic beads were employed. Polyvalent second antibodies or protein-A labelled with enzymes served as tracers. A high frequency of positive sera was found in all groups including fertile controls with tests using whole spermatozoa as antigen. The methods using solubilized antigen preparations showed fewer positives on the whole and correlated better with the various clinical categories of the WHO sera. Whilst there was some agreement in the results between the various laboratories on a few sera, most of the positive sera found by one laboratory were reported as negative by others. More investigative work is needed to improve reproducibility between different laboratories and to reduce non-specific reactions with normal controls. A more precise definition of the proper cut-off levels for positives and negatives is also needed. Despite these short-comings, the development of an ELISA for the diagnosis of sperm-immune infertility cases seems to be justified in the long term.

Antibodies↗
PubMed1985

Comparison of admission and discharge medications in two geriatric populations.

Drug usage patterns were determined from a chart review of two groups of the elderly upon admission to and discharge from the hospital. A comparison was made between a United States group (N = 60) and a Scotland group (N = 60). The most common drugs noted in both groups were cardiovascular drugs (primarily diuretics) and vitamins and minerals. The mean number of drugs per patient in both groups was approximately four, with minimal change in number between admission and discharge. The number of drugs decreased with male sex and increasing age in the United States group and increased with male sex and increasing age in the Scotland group. The Scotland group was on more short-acting benzodiazepines, more bowel medications, more antidepressants, more antiparkinson agents, and fewer respiratory drugs than the United States group. Although both groups tended to have certain drugs deleted, Scotland patients were more likely to have narcotics discontinued and bowel medications added before discharge. These drug usage patterns demonstrate substantial polypharmacy in the elderly and the importance of selecting appropriate drugs in the elderly.

Age Factors↗
PubMed1984

Conjugated normetanephrine in human and rat plasma and erythrocytes.

Enzymatic hydrolysis was applied to the deconjugation of normetanephrine (NMN) in plasma and red blood cell lysate. By this procedure, in human plasma 77% of total NMN circulated in sulfate-conjugated form, while in rat plasma 63% was in glucuronidated form. Total NMN in human lysate was significantly higher than in plasma (P less than 0.001) and was mostly in the free form, indicating that red blood cells may play an important role in metabolism of norepinephrine. Enzymatic hydrolysis is superior to the standard method by acid hydrolysis plus heat since: (1) more conjugated NMN is hydrolyzed in human plasma and (2) a smaller sample is needed for hydrolysis.

Adult↗
PubMed1984

Reduced tyrosine hydroxylase activity in nigrostriatal system of sinoaortic-denervated rats.

Tyrosine hydroxylase activity was measured in the caudate nucleus and substantia nigra (pars compacta) of sinoaortic-denervated (SAD) and sham-operated (SO) rats 3 days after operation. The SAD groups had approximately a 50%, statistically significant, reduction of enzyme activity in both regions and also a significant reduction of dopamine in caudate nucleus. These results suggest a probable link between cortico-somatomotor integration and neural input from arterial baroreceptor neural pathways.

Animals↗
PubMed1984

Plasma levels of free and total catecholamines and two deaminated metabolites in man--rapid deconjugation by heat in acid.

We have described a procedure for deconjugation of plasma catecholamines, norepinephrine (NE), epinephrine (E) and dopamine (DA) and two catecholamine metabolites 3,4-dihydroxymandelic acid (DOMA) and 3,4-dihydroxyphenylglycol (DOPEG). Heat at 100 degrees C of the acidified specimen, pH 0.8, produced complete deconjugation of catecholamines in 7 minutes and of metabolites in 5-7 minutes. Subsequently all five products were simultaneously measured with a radioenzymatic assay. However, hydrolysis for 7 minutes produced approximately a loss of 5% in DA and E, 15% in NE and 50% in the metabolites. The percent of free compound in the plasma of 11 normotensive and healthy subjects was 23 +/- 16 for NE, 20 +/- 8 E, 0.8 +/- 1 DA, 20 +/- 7 DOMA and 42 +/- 12 for DOPEG. Similar results were obtained in a random specimen of six patients with primary hypertension. In a group of four patients with pheochromocytoma free levels of NE, DOPEG and DOMA were significantly greater than in the other two groups, whereas conjugates were not. The intravenous administration of NE or the activation of sympathetic nervous system by standing combined with exercise for 15 minutes did not produce a change in the levels of plasma conjugates. These findings suggest that short changes in plasma catecholamines are better reflected in the free than the conjugated part.

Catecholamines↗