A population-based study of dementia in 85-year-olds.
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Aged↗
Biomedical subjects
M Goldstein
Publications and source records attributed to M Goldstein.
Argon laser gonioplasty in the treatment of angle-closure glaucoma.
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Glaucoma, Angle-Closure↗
Induction of c-fos immunoreactivity in tyrosine hydroxylase and phenylethanolamine-N-methyltransferase immunoreactive neurons of the medulla oblongata of the rat after phosphate-buffered saline load in the urethane-anaesthetized rat.
We have studied the induction of c-fos immunoreactivity (c-fos IR) in catecholaminergic and vasopressinergic immunoreactive neurons after repeated phosphate-buffered saline (PBS) loading or after repeated elicitation of the baroreceptor reflex via repeated infusion of the vasoconstrictor agent L-phenylephrine. About 75% and 30%, respectively, of the tyrosine-hydroxylase immunoreactive (IR) cell bodies of the ventral noradrenaline (NA) A1/adrenaline (A) C1 and dorsal NA A2/A C2 areas and 60% and 30%, respectively, of the phenylethanolamine N-methyltransferase IR nerve cells of the adrenaline C1 and C2 areas and 25% of the vasopressin (VP) IR neurons of the supraoptic (SO) nucleus developed nuclear c-fos IR after repeated PBS loading. This phenomenon remained unaltered by the repeated elicitation of the baroreceptor reflex. These results suggest that the activation of volume receptors promotes homeostatic responses via activation of early genes in subsets of central medullary noradrenaline and adrenaline neurons and SO VP neurons of the urethane-anaesthetized rat.
Amino Acid Sequence↗
The vigilance-promoting drug modafinil counteracts the reduction of tyrosine hydroxylase immunoreactivity and of dopamine stores in nigrostriatal dopamine neurons in the male rat after a partial transection of the dopamine pathway.
We studied the ability of the vigilance-promoting drug modafinil to modulate the anterograde and retrograde changes in tyrosine hydroxylase (TH) immunoreactivity and in dopamine (DA) stores in the nigro-neostriatal DA neurons, following a partial hemitransection of this ascending DA system, using a combined morphometrical, biochemical and behavioural analysis. Modafinil was given daily i.p. in doses of 10-100 mg/kg, starting 15 min after the lesion, and the partially hemitransected rats were killed 2 weeks later. Changes in TH-immunoreactive nerve cell bodies and nerve terminals induced by the partial hemitransection were studied in the substantia nigra and neostriatum in combination with image analysis. The substantia nigra and neostriatum were also subjected to biochemical analysis of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Modafinil treatment dose-dependently (10-100 mg/kg) counteracted the hemitransection-induced disappearance of nigral TH-immunoreactive nerve cell body profiles and neostriatal TH-immunoreactive nerve terminal profiles. A 2-week treatment with 100 mg/kg of modafinil also counteracted the hemitransection-induced depletion of DA stores in the neostriatum and the ventral midbrain. Moreover, the repeated daily treatment with modafinil (100 mg/kg) protected against the hemitransection-induced disappearance of striatal 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and noradrenaline levels. Striatal DA function was analysed by studying apomorphine-induced (1 mg/kg, s.c.) ipsilateral rotational behaviour 4 and 11 days after the operation. A marked dose-dependent reduction of ipsilateral rotational behaviour was demonstrated after the daily modafinil treatment in the partially hemitransected rats. In another model involving unilateral nigral microinjections of 6-hydroxydopamine, acute (one single dose) modafinil (100 mg/kg) did not affect the contralateral rotational behaviour induced by apomorphine (0.05 mg/kg s.c.), when given 30 min before the apomorphine. Taken together, morphological, neurochemical and behavioural evidence has been obtained that anterograde and retrograde changes induced in the DA stores and TH immunoreactivity of the nigro-neostriatal DA neurons by a partial hemistransection are counteracted by modafinil in a dose dependent way with 100 mg/kg producing a significant protective action against impairment of DA transmission. The results of this study open up the possibility that modafinil may protect against the anterograde and retrograde degeneration of nigrostriatal DA neurons seen after mechanically induced injury.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Protective actions of human recombinant basic fibroblast growth factor on MPTP-lesioned nigrostriatal dopamine neurons after intraventricular infusion.
Basic fibroblast growth factor (bFGF, FGF-2) is a trophic factor for neurons and astrocytes and has recently been demonstrated in the vast majority of dopamine (DA) neurons of the ventral midbrain of the rat. Potential neuroprotective actions of FGF-2 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model have also been reported. The actions of the FGF-2 have now been further analyzed in a combined morphological and behavioural analysis in the MPTP model of the adult black mouse, using a continuous human recombinant FGF-2 (hrFGF-2) intraventricular (i.v.t.) administration in a heparin-containing (10 IU heparin/ml) mock cerebrospinal fluid (CSF) solution. Tyrosine hydroxylase (TH) immunocytochemistry in combination with computer assisted microdensitometry demonstrated a counteraction of the MPTP-induced disappearance of neostriatal TH-immunoreactive (ir) nerve terminals following the FGF-2 treatment. Unbiased estimates of the total number of nigral TH ir neurons, using stereological methods involving the optical disector (Olympus), showed that the MPTP-induced reduction in the number of nigral TH ir nerve cell bodies counterstained with cresyl violet (CV; by 56%) was partially counteracted by the FGF-2 treatment (by 26%). The behavioral analysis demonstrated an almost full recovery of the MPTP-induced reduction of the locomotor activity after FGF-2 treatment. This action was maintained also 1 week after cessation of treatment. The hrFGF-2 produced an astroglial reaction as determined in the lateral neostriatum and in the substantia nigra (SN) far from the site of the infusion, indicating that the growth factor may have reached these regions by diffusion to activate the astroglia. Immunocytochemistry revealed FGF-2 immunoreactivity (IR) in the nuclei of the astroglia cell population in the dorsomedial striatum and the microdensitometric and morphometric evaluation demonstrated an increase in the number, but not in the intensity, of these profiles on the cannulated side, suggesting the possibility that hrFGF-2 stimulates FGF-2 synthesis in astroglial cells with low endogenous FGF-2 IR. These results indicate that hrFGF-2, directly and/or indirectly via astroglia, upon i.v.t. infusion exerts trophic effects on the nigrostriatal DA system and may increase survival of nigrostriatal DA nerve cells exposed to the MPTP neurotoxin
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
The postnatal development of tyrosine hydroxylase immunoreactive nerves in rat atrium, studied with immunofluorescence and confocal laser scanning microscopy.
The developmental pattern and distribution of tyrosine hydroxylase (TH) immunoreactive nerves in the rat heart has been studied by indirect immunofluorescence. Anti-TH and monoclonal antibodies against the synaptic vesicle antigen SV2 were applied to whole-mount stretch preparations of the right atria from hearts of newborn to 40-day-old animals. Immunofluorescence was studied with confocal laser scanning microscopy (CFLM). Nerve fibres with TH-like immunoreactivity (TH-LI) were present throughout the atria already at birth, with the highest density around the sino-atrial (SA) node, colocalized in most nerve terminal arborizations with the synaptic vesicle marker SV2. Also, TH-positive ganglion cells were present around the openings of the caval veins. In comparison with TH-positive fibres, SV2-positive nerve terminal fibres were more delicate, and the number of fibres larger in all areas studied. In axon bundles, TH-LI was very prominent, while the SV2-LI was weak. A gradual increase in the density of innervation was observed up to the age of 40 days. The density of innervation decreased from the epicardium to the endocardium, confirmed in cross-sections of the cardiac wall. The relative density of TH-positive nerve terminals was estimated in the CFLM from the area around the SA node. At birth, about 600 white (strongly fluorescent) pixels were registered per scanned field, with the pixel number increasing gradually up to 20,000 pixels per frame in 18- and 40-day-old animals. The results show that TH-positive, possibly adrenergic, nerve fibres are present at birth, and that the pattern is qualitatively similar to that observed in adults, with the expression of synaptic vesicle antigen being present some days before the development of noradrenaline neuroeffector maturation, as shown in a number of physiological and pharmacological studies.
Animals↗
Effects of antibodies against acetylcholinesterase on the expression of peptides and catecholamine synthesizing enzymes in the rat adrenal gland.
In the rat, systemic administration of murine monoclonal antibodies against acetylcholinesterase caused rapid piloerection and ptosis (within 30-60 min after the injection). Using indirect immunohistochemistry the effect of these antibodies on peptides and enzyme expression was studied in the rat adrenal gland. Four days after antibody administration a total disappearance of acetylcholinesterase-immunoreactive fibers was observed. However, groups of acetylcholinesterase-immunoreactive chromaffin cells and intramedullary ganglion cells, both cell types showing acetylcholinesterase immunoreactivity also in the control adrenal medulla, expressed increased immunoreactivity. Analysis revealed that the acetylcholinesterase-immunoreactive chromaffin cell groups lacked phenylethanolamine-N-methyltransferase staining both in controls and treated rats. Antibody administration also affected levels of several peptides present in nerve fibers and chromaffin cells. Thus, the number of cells expressing enkephalin, calcitonin gene-related peptide and galanin was dramatically increased compared to the very few cells observed containing these three peptides in the normal gland. The majority of cells expressing enkephalin after antibody treatment also showed phenylethanolamine-N-methyltransferase immunoreactivity. In contrast, the few chromaffin cells expressing strong enkephalin-like immunoreactivity in controls were phenylethanolamine-N-methyltransferase negative. The sparse networks of calcitonin gene-related peptide- and galanin-positive fibers found in control adrenals were unchanged after the antibody treatment. However, the dense network of enkephalin varicose fibers totally disappeared after the antibody injection. A few substance P- and somatostatin-immunoreactive cells, not present in the normal gland, appeared after administration of the antibodies, whereas no changes were encountered with regard to immunoreactive nerve fibers. No clear differences between normal and treated animals could be observed in chromaffin cells with regard to immunoreactivity for neuropeptide Y or any of the four catecholamine-synthesizing enzymes, tyrosine hydroxylase, aromatic 1-amino acid decarboxylase, dopamine beta-hydroxylase or phenylethanolamine-N-methyltransferase. The present findings demonstrating a disappearance of acetylcholinesterase- and enkephalin-immunoreactive nerve fibers in the adrenal gland after intravenous injection of acetylcholinesterase antibodies support earlier reports showing that these antibodies cause degeneration of preganglionic fibers, and that neuronal decentralization of the adrenal gland induces marked increases in the levels of several peptides in chromaffin cells.
Acetylcholinesterase↗
Microsurgical vasoepididymostomy: refinements and results.
We describe 110 consecutive evaluable vasoepididymostomy procedures performed on 107 azoospermic men who had either bilateral epididymal obstruction, or unilateral obstruction with an absent or nonfunctional contralateral testis. End-to-end procedures were performed in 93 cases and end-to-side anastomoses were done in 17. Previously described surgical techniques were modified to perform the second layer anastomosis between the vasal sheath and the epididymal tunic, instead of using the muscular layer of the vas. Although patency and pregnancy rates were similar after both types of procedures, 40% of the men again became azoospermic after an end-to-side anastomosis, whereas the stricture rate was only 13% after vasoepididymostomy using an end-to-end anastomosis. Of the 107 men 91 have been followed for at least 1 year postoperatively or have achieved a pregnancy with their partner, and 64 (70%) had sperm in the ejaculate postoperatively. Ten men had partners with female factor infertility and none of these couples achieved pregnancy. The overall pregnancy rate was 25 of 81 couples (31%) without female factor infertility. Of the 64 men with patent anastomoses 25 (39%) contributed to a pregnancy postoperatively. Excluding the 7 men with patent anastomoses but definite female factor infertility, the pregnancy rate was 25 of 57 (44%).
Anastomosis, Surgical↗
Relationship between varicocele size and response to varicocelectomy.
We studied the relationship between varicocele size and response to surgery in 86 men with a unilateral left varicocele who reported either infertility (83), pain (1) or pain and testicular atrophy (2). Varicoceles were graded according to size: grade 1--small (22 patients), grade 2--medium (44) and grade 3--large (20). Sperm count, per cent motility, per cent tapered forms and fertility index (sperm count times per cent motility) were measured preoperatively and postoperatively. Preoperatively, men with grade 3 varicocele had lower sperm counts and poorer fertility indexes compared to men with grades 1 and 2 varicocele. Sperm concentration improved significantly in men with grade 2 (33 +/- 5 million per cc preoperatively to 41 +/- 6 million postoperatively, p < 0.04) and grade 3 (18 +/- 5 million preoperatively to 32 +/- 7 million postoperatively) varicocele after microsurgical ligation of the varicocele. Motility improved significantly in men with grade 3 varicocele. Decrease in per cent tapered forms was significant in all groups. A comparison of per cent change in fertility index among the groups revealed that men with grade 3 varicocele improved to a greater degree (128%) than men with grade 1 (27%) or grade 2 (21%) varicocele. Pregnancy rates 2 years postoperatively were 40% for grade 1, 46% for grade 2 and 37% for grade 3 varicocele patients. The difference in pregnancy rates among the groups was not statistically significant. In conclusion, infertile men with a large varicocele have poorer preoperative semen quality but repair of the large varicocele in those men results in greater improvement than repair of a small or medium sized varicocele.
Adult↗
Surgical therapy of male infertility.
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Constriction, Pathologic↗
Acrosome reaction inducing activity in follicular fluid correlates with progesterone concentration but not with oocyte maturity or fertilizability.
Follicular fluid is a potent mediator of sperm acrosome reaction (AR) in vitro. The aim of this study was to investigate whether individual follicular fluids vary quantitatively in their ability to stimulate an AR, and whether such variability relates to fertilizability of the corresponding egg, its maturational level and/or progesterone content. Individual follicular fluids were obtained from 24 women undergoing in-vitro fertilization and assayed for their ability to induce an AR in normal human spermatozoa. After incubation in capacitation medium for 18 h, spermatozoa were challenged with the individual follicular fluids for 30 min. AR was detected by immunofluorescence, using fluorescein-labelled Pisum sativum lectin. We found that individual follicular fluids varied markedly in their ability to induce AR. Acrosome reaction correlated linearly with progesterone concentration (Spearman's r = 0.735, P = 0.01) at constant protein level, but no correlation was found between AR and protein concentration at constant progesterone level. Progesterone concentrations were not only higher (ANOVA, P = 0.002) in fluids from mature oocytes compared to those from less mature or post-mature eggs but also in fluids from fertilized compared to unfertilized eggs (ANOVA, P = 0.015, n = 13 patients with both fertilized and unfertilized eggs). In contrast, AR-inducing ability of individual follicular fluids did not differ for fertilized and unfertilized eggs. While AR-inducing ability appeared to increase with maturational stage of the egg, this trend was not statistically significant, probably due to small sample size. Our data suggest that progesterone rather than protein is the principal mediator of acrosome reaction induced by follicular fluid in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Acrosome↗
Administration of nebivolol after coronary artery bypass in patients with altered left ventricular function.
This prospective, double-blind study used invasive monitoring and echo-Doppler techniques to compare the hemodynamic effects of nebivolol, a new beta 1-selective beta-blocking agent with those of atenolol in patients recovering from coronary artery bypass grafting surgery. Five milligrams nebivolol and 50 mg atenolol equally decreased heart rate (HR) and blood pressure (BP) but, nebivolol, in contrast to atenolol, caused no decrease in stroke index (SI), cardiac index (CI), and right ventricular ejection fraction (RVEF). These differences appeared to be related in part to different peripheral effects of the two agents because nebivolol administration was associated with a reduction in systemic vascular resistance (SVR). After < or = 10 days of treatment, acceleration of aortic flow velocity increased and isovolumic relaxation time decreased with nebivolol but not with atenolol treatment. Both drugs were equally well tolerated. Therefore, nebivolol shares most of its effects with classical beta 1-blockers but is devoid of the potentially harmful effects on cardiac output (CO) and peripheral resistance.
Adrenergic beta-1 Receptor Antagonists↗
Decade of the brain: National Institute of Neurological Disorders and Stroke.
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Animals↗
Effects of verapamil and diltiazem on dopamine release in the central nervous system of spontaneously hypertensive rats.
1. The purpose of the present study was to investigate the effects of Ca(2+)-antagonists (verapamil and diltiazem) on dopamine release in the central nervous system in hypertension. 2. Striatal slices obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were prelabelled with [3H]-dopamine, and superfused with Krebs-Ringer solution in vitro. The slices were stimulated electrically at a frequency of 1 Hz. 3. Stimulation-evoked release of [3H]-dopamine from striatal slices was significantly decreased in SHR compared with WKY rats. 4. Exposure of slices to verapamil and diltiazem significantly increased the stimulation-evoked [3H]-dopamine release. The facilitatory effects of the Ca(2+)-antagonists on dopamine release were significantly greater in SHR than in WKY rats. 5. Because central nervous system dopaminergic mechanisms appear to be depressor, the results suggest that the pronounced effects of verapamil and diltiazem on dopamine release in SHR might be involved in the central hypotensive mechanisms of the Ca(2+)-antagonists.
Animals↗
Effects of bradykinin on [3H]-norepinephrine release in rat hypothalamus.
1. We examined the regulatory actions of bradykinin on norepinephrine release in the hypothalamus of rats. 2. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices of Sprague-Dawley rats in a dose-dependent manner (1 Hz: S2/S1 ratio, mean +/- s.e.m., control 0.868 +/- 0.016, n = 6; bradykinin 1 x 10(-6) mol/L 1.039 +/- 0.018, n = 6, P < 0.05; bradykinin 3.3 x 10(-6) mol/L 1.130 +/- 0.064, n = 6, P < 0.05). The basal release of [3H]-norepinephrine was not affected by the peptide. 3. Bay K 8644, a dihydropyridine-sensitive calcium channel agonist, significantly potentiated the facilitatory effect of bradykinin on norepinephrine release, although Bay K 8644 by itself had no significant effect. By contrast, nicardipine, a dihydropyridine-sensitive calcium channel blocker, reversed the increase in norepinephrine release induced by bradykinin and Bay K 8644. 4. These results indicate that bradykinin may increase norepinephrine release in rat hypothalamus, partially mediated by interactions with dihydropyridine-sensitive calcium channels.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Amaurosis fugax in young adults.
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Adult↗
A novel method for rapid enrichment of lactotrophs from dispersed anterior pituitary cells of the rat.
A polyclonal antibody to the rat D2 dopamine (DA) receptor was rapidly and covalently attached to surface-activated polystyrene cultureware (MicroCEL-Lector plates). Addition of a suspension of dispersed rat anterior pituitary cells resulted in the rapid (within 1 h) selection of cells possessing D2 DA receptors (i.e. lactotrophs). Four-fold enrichment (from about 20% in the suspension to about 80%) was routinely obtained, as judged by prolactin (PRL) immunostaining. The enriched cells were virtually free of fibroblasts and were much more homogeneous in appearance than untreated cells after 3 days in culture. Lactotroph-enriched cell cultures displayed similar functional characteristics as untreated cells when assessed by determining dose-response curves for inhibition of PRL secretion by the DA agonist N-propylnorapomorphine. This method may be generally applicable for the selective enrichment and purification of desired cell types from heterogeneous mixtures in tissue dispersions.
Amino Acid Sequence↗
The influence of spring and summer New England meteorologic conditions on the respiratory status of patients with chronic lung disease.
To determine whether meteorologic conditions affect the respiratory status of individuals with chronic lung disease, we asked 14 patients who had completed outpatient pulmonary rehabilitation to record the following information daily during the spring and summer of 1991: (1) dyspnea on arising (morning dyspnea); (2) dyspnea throughout the day (daytime dyspnea); (3) peak expiratory flow rate (PEFR); (4) mood; and (5) the presence of lower respiratory tract infection (LRI). The effect of local meteorologic conditions and LRI frequency on morning and daytime dyspnea, PEFR, and mood were analyzed for spring and summer seasons using a linear regression technique that controlled for first-order autocorrelation. The LRI frequency and the preceding day's respiratory status were the most significant predictors of either season's daily variation in respiratory status. During spring, the only meteorologic condition associated with respiratory status was precipitation: rainfall was directly related to increased morning and daytime dyspnea. Meteorologic conditions were not related to changes in PEFR or mood. During summer, the combination of higher temperature, rise in barometric pressure, and increased LRI frequency best predicted increased morning dyspnea, while the combination of higher temperature and rise in barometric pressure best predicted reduced PEFR. Meteorologic conditions were not related to changes in daytime dyspnea or mood. Precipitation in spring and a combination of high temperature and rise in barometric pressure in summer best predicted deterioration in the respiratory status of this group of patients with chronic lung disease.
Aged↗