Search PubMed⌕ Search

Biomedical subjects

M Goldstein

Publications and source records attributed to M Goldstein.

At least 361 records · Page 20Linked to original sources
PubMed1988

Failure of gonadotropin therapy secondary to chorionic gonadotropin-induced antibodies.

Seventeen years after first receiving treatment with hCG (at age 8 yr), a man with hypogonadotropic hypogonadism no longer responded to gonadotropin therapy. He had received hCG for 6 months when he was 8 yr old, from age 18-21 yr and from age 21-25 yr, when the resistance developed. Anti-hCG antibodies were found in his serum. Three sequential treatment regimens were tried to obviate the effect of these antibodies. 1) hCG treatment (2000 IU, three times per week) concomitant with weekly plasmapheresis (since the patient's response to an hCG challenge test was improved after a reduction of antibody titer by plasmapheresis) resulted in only a temporary increase in testosterone production. 2) Treatment with human (h) LH (400 IU/week) and hFSH (25 IU/week) was used because of the low cross-reaction of the antibodies with hLH and a response to a hLH-challenge test. This treatment maintained serum testosterone levels within the normal range for long periods, but had to be discontinued when the supply of hLH was exhausted. 3) Pulsatile LHRH administration (25 ng/kg, sc, every 2 h) for 2 months did not induce the release of pituitary gonadotropins. These results indicated that 1) conventional hCG treatment was impaired by antibody-induced changes in the kinetics of hCG after its im administration; 2) hLH was an effective substitute for hCG, and the combined hLH-hFSH administration initiated a moderate amount of spermatogenesis; and 3) the patient differs from most individuals with hypogonadotropin hypogonadism in that he did not have normal responses to repetitive LHRH administration.

Antibodies↗
PubMed1988

Prorenin secretion from human testis: no evidence for secretion of active renin or angiotensinogen.

To determine if the testis secretes active renin and prorenin, we collected internal spermatic venous blood from 29 young men undergoing varicocelectomy and measured plasma prorenin and active renin together with angiotensinogen and testosterone. Prorenin was higher in internal spermatic venous plasma than in peripheral plasma (+5.3 +/- 1.2 (+/- SE) ng/mL.h [+1.21 ng/(L.s)]; P less than 0.001) as was testosterone [+344 +/- 32 ng/mL [(+1193 nmol/L; P less than 0.001], but there was no significant difference in either active renin (-0.74 +/- 0.45 ng/mL.h [-0.17 ng/(L.s)] or angiotensinogen [+12 +/- 24 ng/mL (+0.01 mumol/L)]. These results demonstrate that the testis secretes prorenin, but not active renin or angiotensinogen, into the general circulation. They support the hypothesis that extrarenal renin systems cannot process prorenin to renin.

Adult↗
PubMed1987

Chronic haloperidol affects striatal D2-dopamine receptor reappearance after irreversible receptor blockade.

The time course of recovery of [3H]spiperone binding in the rat striatum after administration of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was studied in chronically haloperidol-treated rats (0.5 mg/kg, i.p., twice a day for two weeks). Chronic neuroleptic treatment significantly enhanced the [3H]spiperone Bmax value. EEDQ (6.0 mg/kg, i.p.) produced a similar profound decrease of [3H]spiperone binding site density in both saline- and haloperidol-treated rats. However, the receptor degradation rate constant in the haloperidol-treated animals (k = 0.0051 h-1) and the receptor production rate (r = 1.6 fmol/mg prot/h) were lower than in the saline-treated rats (k = 0.0074 h-1; r = 1.8 fmol/mg prot/h). These results are different from what is found in 6-OH-dopamine lesioned rats. D2-receptor recovery after EEDQ administration is enhanced in chronically (4-5 weeks) denervated striatum (Brain Research, 329 (1985) 225-231) while the degradation rate constant is unchanged. Thus, the present results indicate that chronic haloperidol treatment reduces both the degradation and production rates of striatal D2-receptors.

Animals↗
PubMed1987

The innervation of intraocular spinal cord transplants by cografts of locus ceruleus and substantia nigra neurons.

The nucleus locus ceruleus and the substantia nigra were sequentially cografted with spinal cord in the anterior chamber of the eye of adult rats. The double grafts were allowed to mature in oculo. After a survival time of 2 months, half of the number of rats were sacrificed, the grafts were dissected out and prepared for tyrosine hydroxylase immunohistochemistry and Falck-Hillarp monoamine histochemistry. The remaining animals were sacrificed after 12-14 months and processed according to the same protocol. No ingrowth from the sympathetic ground plexus in the host iris was seen in single spinal cord grafts at any of the survival times. At the shorter survival time there were no or very few catecholaminergic nerve fibers from the locus ceruleus or substantia nigra that were innervating the spinal cord cograft. In double grafts that were allowed to remain in oculo for 12-14 months, the entire spinal cord graft was innervated with varicose, catecholamine-containing nerve fibers. The locus grafts were able to innervate the spinal cord cografts much more densely than the substantia nigra grafts. In conclusion, the results demonstrate that isolated intraocular spinal cord grafts can be innervated by adjacent central catecholamine neurons. However, this is done in a delayed manner as compared to other models. The isolated replicas of descending adrenergic pathways to the spinal cord thus formed should provide useful information about the function of descending spinal catecholamine pathways.

Animals↗
PubMed1987

The effect of neuropeptide Y (NPY) on stimulation-evoked release of [3H]norepinephrine (NE) from rat hypothalamic and cerebral cortical slices.

The effects of neuropeptide Y (NPY) on stimulation-evoked release of [3H]norepinephrine ([3H]NE) in rat hypothalamic and cerebral cortical slices were investigated. NPY inhibits the stimulation-evoked release of [3H]NE from hypothalamic, but not from cerebral cortical slices. NPY potentiates the inhibition of [3H]NE release by the alpha 2-agonist UK 14,304 in the hypothalamic slices. The blockade of alpha 2-adrenoceptors by RX 781094 diminishes the inhibitory effects of NPY. These results suggest that in the hypothalamic slices the action of NPY might be in part mediated by the alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1987

Evidence for a fast receptor turnover of D1 dopamine receptors in various forebrain regions of the rat.

The time course for recovery of binding of the D1 dopamine receptor antagonist radioligand [3H]SCH 23390, after administration of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), was studied in the neostriatum, nucleus accumbens, tuberculum olfactorium and claustrum of the rat by means of quantitative receptor autoradiography. The results showed that the receptor degradation rate constant (k) ranged from 0.0163 to 0.0315 h-1 and that the receptor production rate (r) ranged from 8.52 to 24.96 fmol/mg protein/h. These results indicate that the D1 receptor has a considerably faster turnover than the D2 receptor, which suggests that the D1 receptor may require a dynamic regulation including also changes in receptor production and degradation rates.

Animals↗
PubMed1987

Localization of tyrosine hydroxylase-immunoreactive neurons in the cat hypothalamus, with special reference to fluorescence histochemistry.

The present study examines the distribution and morphological characteristics of neurons containing immunoreactivity of tyrosine hydroxylase in the cat hypothalamus. We used the indirect immunoperoxidase technique on vibratome sections. Tyrosine hydroxylase-immunoreactive cell bodies were widely distributed in discrete regions of the cat hypothalamus. Several principal cell groups were identified. They were seen in the posterior and dorsal hypothalamic areas, zona incerta, dorsomedial and lateral hypothalamic areas, arcuate nucleus, periventricular nucleus, paraventricular nucleus, and an area of the tuber cinereum and preoptic area. These cells presented two different morphological characteristics; small with two to three short processes and medium to large, multipolar with three to five long dendritic trees. The atlas is presented in twelve cross-sectional drawings of the cat hypothalamus from the level A8.5 to A15 of the Horsley-Clarke stereotaxic planes. We also examined the distribution of hypothalamic catecholamine fluorescent neurons by using the aqueous aldehyde method in combination with glyoxylic acid applied to vibratome sectioned tissues, which improves sensitivity. Comments are made on the relative localizations of the tyrosine hydroxylase-immunoreactive and aldehyde-induced histofluorescent cells, as well as on species differences between the cat, rat, and mouse.

Animals↗
PubMed1987

Determination of monoamines by use of liquid chromatography with electrochemical detection in the study of selective monoamine neurotoxins.

Determination of regional monoamine levels in the CNS in the study of the effects of selective monoaminergic neurotoxins is a reliable method with which to study the morphological changes in denervated as well as re- or hyperinnervated regions as evidenced by comparisons with several other methods. In the acute stage, the changes in monoamine levels reflect both the beginning of the degeneration and the acute pharmacological effects exerted by several monoaminergic neurotoxins. The only exception to this seems to be the MPTP-induced chronic decrease of DA in the nucleus accumbens and the tuberculum olfactorium where no morphologic changes have been found so far.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Cell-free detection and characterization of a novel nerve growth factor-activated protein kinase in PC12 cells.

We have developed a cell-free assay to detect and characterize nerve growth factor (NGF)-activated protein kinase activity. Cultured PC12 cells were briefly exposed to NGF, and extracts of these were assayed for phosphorylating activity using exogenously added tyrosine hydroxylase as substrate. Tyrosine hydroxylase was employed since it is an endogenous substrate of NGF-regulated kinase activity and is activated by phosphorylation. In the cell-free assay, extracts prepared from NGF-treated cells yielded a 2-3-fold greater incorporation of phosphate into tyrosine hydroxylase as compared with extracts of control, NGF-untreated cells. Activation did not occur, however, if NGF was added directly to cell extracts. The NGF-stimulated phosphorylating activity appeared to be due to regulation of a protein kinase rather than of a phosphoprotein phosphatase. Characterization of the kinase (designated as kinase N) showed that it is soluble, is detectably activated within 1-3 min after cells are exposed to NGF and maximally activated by 10 min, is half-maximally activated with 0.5 nM NGF and maximally activated with 1 nM NGF, is detectable in the presence of either Mg2+ or Mn2+ but does not require Ca2+, does not require nonmacromolecular cofactors, can use histone H1 as a substrate, and exhibits a 2-fold increase in apparent Vmax in response to NGF but does not undergo a significant change in apparent Km for either ATP or GTP. A number of characteristics of kinase N were assessed including susceptibility to inhibitors, substrate specificity, cofactor requirements, ATP dependence, and lack of down-regulation by prolonged expose to a phorbol ester. These studies indicated that it lacks tyrosine kinase activity and is distinct from a variety of well-characterized protein kinases including cAMP-dependent protein kinase, protein kinase C (Ca2+/phospholipid-dependent enzyme), Ca2+/calmodulin-dependent kinase, and casein kinase II. Preliminary purification data show that the kinase has a basic pI and that it has an apparent Mr of 22,000-25,000. The only amino acid in tyrosine hydroxylase found to be phosphorylated by the semipurified kinase is serine.

Adrenal Gland Neoplasms↗
PubMed1987

Evidence for an inhibitory effect of the peptide galanin on dopamine release from the rat median eminence.

The role of the neuropeptide galanin (GAL) in rat hypothalamus has been studied in different experimental models. Thus, the effect of GAL on potassium-induced dopamine release was analyzed in vitro, and the localization of GAL and GAL binding sites was studied with immunohistochemistry and receptor autoradiography, respectively. In the median eminence GAL and presumably dopamine were found to coexist in nerve endings and this area contained a high density of 125I-GAL binding sites. In vitro experiments revealed that GAL inhibited the release of [3H]dopamine in a dose-dependent manner (IC50 = 7-10 nM), possibly via a presynaptic receptor.

Animals↗
PubMed1987

Dopaminergic cells in the caudal A13 cell group express somatostatin-like immunoreactivity.

The caudal extension of the hypothalamic A13 dopamine cell group (A13c) was studied in the rat brain with immunohistochemical techniques using antibodies raised against the dopamine synthesizing enzymes tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). Adjacent sections revealed that the TH- and AADC-staining patterns exhibited a clear overlap with that for somatostatin (SOM). Employing a double-labelling method with SOM- and AADC-antisera and subsequent elution and restaining of the same section with TH-antiserum, it was found that all immunoreactivities occurred in the same cell bodies. This study gives the first evidence for the presence of SOM-immunoreactivity in dopamine neurons.

Animals↗
PubMed1987

The synthesis of NPY and DBH is independently regulated in adrenergic nerves after reserpine.

A newly developed cytofluorimetric scanning technique was applied in a pharmacological study to investigate the influence of reserpine (10 mg/kg) on the axonal transport of norepinephrine (NE), dopamine-beta-hydroxylase (DBH), tyrosine hydroxylase (TH), and neuropeptide Y (NPY)-like immunoreactivities (LI) in the adrenergic axons of the sciatic nerve of rat. Early after reserpine (18 hr and 24 hr after the reserpine injection) the amounts of NE accumulated proximal to a 12-hr crush were nil or very low, as observed in earlier studies. DBH-LI, TH-LI, and NPY-LI accumulations were also depressed but only to about 50% of control accumulations. This decrease in amounts of transported substances was probably caused by a decrease in protein synthesis and also a lowered velocity of fast axonal transport initially after reserpine, when body temperature is low. The amounts of accumulated NE, DBH-LI, TH-LI, and NPY-LI were normalized around day 2 after reserpine, but on day 4 NE, DBH-LI, and in some rats also TH-LI accumulated in supra-normal amounts. However, NPY-LI accumulations were normal, indicating that DBH, but not NPY, was trans- synaptically induced in rat sympathetic neurons, and that the biochemical composition of axonally transported organelles is altered for some days after reserpine.

Adrenergic Fibers↗
PubMed1987

The characterization of the dopaminergic profile of EMD 23,448, and indolyl-3-butylamine: selective actions on presynaptic and supersensitive postsynaptic DA receptor populations.

The effects of the dopamine (DA) agonist EMD 23,448 on central normosensitive and supersensitive DA receptors were investigated. EMD 23,448 only slightly inhibits rat striatal DOPA synthesis in vivo and does not inhibit the enhanced striatal DOPA synthesis elicited by acute administration of haloperidol. Also unlike other DA agonists it does not increase striatal acetylcholine levels. However, it inhibits striatal DOPA synthesis in rats with DA receptors rendered supersensitive by chronic treatment with haloperidol. EMD 23,448 also effectively inhibits the enhanced striatal DOPA synthesis elicited by administration of GBL. Furthermore, EMD 23,448 selectively reduces, in a dose-dependant way, DA utilization in nerve terminals of the central caudate and in dotted terminals of the ventral striatum but DA utilization in the substantia nigra is unaffected. The most marked reduction of DA utilization was induced in the anteromedial frontal cortex. These results indicate that EMD 23,448 selectively stimulates presynaptic DA receptors and supersensitive postsynaptic DA receptors. Behavioral experiments in animals with normosensitive and supersensitive DA receptors also indicate that EMD 23,448 effectively stimulates presynaptic and supersensitive postsynaptic DA receptors. Receptor binding studies have shown that EMD 23,448 has a high affinity for the D2 DA receptors, but it ineffectively promotes the coupling of the DA receptors with the guanine nucleotide regulatory protein. However, at supersensitive striatal DA receptors the coupling is shown to be enhanced by EMD 23,448. The selectivity of EMD 23,448 for presynaptic DA receptors might, at least in part, be related to the presence of DA receptor reserves which are sensitive to EMD 23,448. With regard to the selectivity of EMD 23,448 for supersensitive postsynaptic DA receptors an increase in the efficiency of the coupling mechanism upon activation by EMD 23,448 is probably involved.

Acetylcholine↗
PubMed1987

Correlation between intracavernous papaverine injection and Doppler analysis in impotent men.

One hundred impotent men were evaluated with Doppler pulse-wave analysis and intracavernous papaverine. Fifty-four men with normal Doppler study response had abnormal responses to papaverine. A normal Doppler study response failed to predict the inability of papaverine to induce an erection in 54 per cent of cases. Twenty-seven patients had abnormal Doppler study responses, and only 2 of these men had a normal response to papaverine. An abnormal Doppler study response was highly predictive of a vascular abnormality.

Erectile Dysfunction↗
PubMed1987

D-1 and D-2 agonists in Parkinson's disease.

We have evaluated 5 DA agonists-bromocriptine, lergotrile, lisuride, pergolide, and mesulergine in studies encompassing 278 patients with advanced PD. In most of our patients the DA agonist was added to levodopa. Most of our patients were no longer satisfactorily responding to levodopa. Previous attempts at managing these patients by changing the dose of levodopa (increasing or decreasing it), the treatment schedule, or the ratio of levodopa to carbidopa or by temporarily discontinuing levodopa [drug holiday] were unsuccessful. The majority of our patients had diurnal fluctuations in performance, either "wearing off" or "on-off" phenomena. The addition of a DA agonist resulted in a decrease in parkinsonian disability in most patients and a decrease in the severity of the diurnal fluctuations in performance. Improvement in many patients was maintained for at least 2 years. Adverse effects included mental changes, dyskinesias, orthostatic hypotension, and nausea. All of the adverse effects were reversible when the agonist was decreased or discontinued. As a group the agonists behaved similarly but individual patients often responded better to one agonist than another. The main role of agonists is in combination with levodopa in the treatment of patients with early PD who have not yet developed dyskinesias or diurnal fluctuations in performance.

Aged↗
PubMed1987

Evidence for discrete alterations in central cardiovascular catecholamine and neuropeptide Y immunoreactive neurons in aged male rats and in genetically hypertensive male rats of the Lyon strain.

A computer-assisted morphometrical and microdensitometrical analysis has been performed on cardiovascular noradrenaline (NA), adrenaline (A) and neuropeptide (Y (NPY) neurons in adult and 24-month-old male rats and on hypotensive (LL), normotensive (LN) and hypertensive (LH) male rats of the Lyon strain using the indirect immunoperoxidase procedures. It was found that in NPY/phenylethanolamine-N-methyltransferase (PNMT) costoring neurons of the CI area of the rostral medulla oblongata NPY-like immunoreactivity showed a more marked reduction than the PNMT immunoreactivity. Furthermore, within the parvocellular part of the paraventricular hypothalamic nucleus. NPY immunoreactive nerve terminal profiles were much more affected than the PNMT immunoreactive profiles during aging as revealed by a marked reduction in the number of profiles and by a marked reduction of absorbency values in the microdensitometrical analysis. Thus, in the NPY/PNMT costoring neurons of the A C1 group of the ventrolateral medulla projecting, for example, to the hypothalamus, the peptide transmission line may have a special vulnerability to the aging processes which may contribute to the development of hypertension in old people in view of a vasodepressor role of many central NPY/PNMT neurons. An extensive morphometrical and microdensitometrical analysis of the various catecholamine (CA) cell groups of the medulla oblongata of the LL, LN and LH rats of the Lyon strain was performed. In a comparison between LL and LH rats the A2 cell group of the LH strain showed a trend for an increase in the mean tyrosine hydroxylase (TH) immunoreactive cell body area and the C3 group showed a significant increase in the number of PNMT immunoreactive profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗