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M Goldstein

Publications and source records attributed to M Goldstein.

At least 487 records · Page 27Linked to original sources

Transient expression of selected catecholaminergic traits in cranial sensory and dorsal root ganglia of the embryonic rat.

We describe the transient expression of catecholaminergic traits in cranial sensory and dorsal root ganglia of the embryonic rat in vivo. Isolated cells expressing tyrosine hydroxylase (T-OH) immunoreactivity were initially detected in trigeminal (V) ganglion anlages as early as gestational Day 10.5 (E10.5; 18-22 somites). Neurofilament (NF) protein was also evident in V at these early stages. By E11.5 (27-30 somites) clusters of T-OH-positive cells were visible in V. Many of these cells were bipolar; others sent processes into the primitive brainstem. In addition, cells expressing T-OH were apparent in primordia of sensory ganglia serving the glossopharyngeal (IX) and vagal (X) cranial nerves. By this stage (E11.5) all cranial sensory ganglia were rich in NF protein, but immunoreactivity was confined to cellular processes rather than perikarya. By E12 (35-37 somites), only a few, faintly positive T-OH-containing cells were evident in V. However, DBH- and T-OH-positive cells were visible within the more caudal nodose and petrosal ganglia. Furthermore, isolated bipolar cells expressing T-OH were detected in rostral dorsal root ganglia at this stage. Catecholamine fluorescence could not be detected in any sensory ganglia even after maternal treatment with inhibitors of monoamine oxidase. Catecholaminergic cells were not seen at any stage in anlages of the acousticovestibular nucleus. Immunoreactive T-OH was undetectable in all ganglia by E13.5 (46-48 somites). These findings highlight the fact that transient expression of the catecholamine phenotype during development is a widespread phenomenon, evident in a variety of cell types of diverse embryonic origin.

Age Factors↗

Glucocorticoid regulation of phenylethanolamine N-methyltransferase (PNMT) in organ culture of superior cervical ganglia.

Glucocorticoid regulation of the adrenergic enzyme, phenylethanolamine N-methyltransferase (PNMT) was studied in organ cultures of the superior cervical ganglion (SCG) from newborn rats. Although PNMT catalytic activity was present in control ganglia, enzyme levels were too low to allow visualization of PNMT immunofluorescent cells. Addition of dexamethasone (DEX) or corticosterone to the medium resulted in a large increase in PNMT activity and bright PNMT immunoreactive (PNMT-IR) staining in cells resembling small, intensely fluorescent (SIF) cells. Addition of non-glucocorticoid steroids was ineffective. Exposure to a brief, 2-hr pulse of DEX (10(-6) M) in vitro elicited the same increase in PNMT as continual exposure to DEX. Studies using metabolic inhibitors demonstrated that the steroid-dependent increase in PNMT activity required both protein and RNA synthesis. Furthermore, the increase was inhibited by cytochalasin B and by the glucocorticoid receptor antagonists, DEX 21-mesylate and cortisol 21-mesylate. These observations suggest that glucocorticoids increase PNMT protein in SIF cells by interacting with specific steroid receptors that undergo translocation to the nucleus.

Animals↗

Differential co-existence of neuropeptide Y (NPY)-like immunoreactivity with catecholamines in the central nervous system of the rat.

The distribution of neuropeptide Y immunoreactive cell bodies in relation to various types of catecholamine-containing cell bodies in the rat brain was analyzed immunohistochemically using antisera to tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase. Coexistence of the peptide in catecholamine cell bodies was established by using an elution-restaining procedure. Neuropeptide Y-like immunoreactivity was observed in most noradrenergic cell bodies of the Al/Cl cell groups in the ventro lateral medulla oblongata. Similarly this peptide immunoreactivity was also observed in the majority of the adrenergic cell bodies of the C2 group. In the dorsal and dorsal-lateral part of the nucleus of the solitary tract, where a group of small adrenergic cells is present, several small neuropeptide Y immunoreactive cells were also observed. The possibility of coexistence of adrenaline and neuropeptide Y in these cells remains to be established. The majority of the noradrenergic cell bodies of the A2 group, as well as the presumptive dopaminergic cells within its ventromedial part, seemed to lack neuropeptide Y-like immunoreactivity. Many noradrenergic cell bodies of the A6 group in the locus coeruleus proper were neuropeptide Y-immunoreactive, whereas the peptide could not be observed in the subcoeruleus group. Neither the A5 and A7 noradrenergic cells in the pons, nor any of the dopaminergic cell groups in the mesencephalon and forebrain (A8-A15) seemed to contain a neuropeptide Y-like peptide. The findings indicate that central catecholamine neurons can be subdivided into distinct sub-groups based upon the coexistence of a specific peptide.

Animals↗

Dopamine and cholecystokinin immunoreactive neurons in mesencephalic grafts reinnervating the neostriatum: evidence for selective growth regulation.

Pieces of embryonic mesencephalic tissue rich in dopamine and cholecystokinin immunoreactive neurones were grafted to the dorsal surface of the caudate-putamen of adult host rats subjected to unilateral dopamine depleting lesions. After 3 months, neuronal survival in the graft and fibre outgrowth into the host brain were studied by tyrosine hydroxylase and cholecystokinin immunohistochemistry, both in serial sections and by elution and restaining of the same sections. Both dopamine- and cholecystokinin-containing neurones as well as neurons containing both compounds survived the transplantation process. The ratio of neurones in which dopamine and cholecystokinin-like immunoreactivity occurred independently and in coexistence was similar in the grafts to that seen in the intact ventral mesencephalon. This suggests that the grafted cells maintain and express at least some of their normal chemical characteristics in the ectopic cortical location. Only those fibres which contained tyrosine hydroxylase but apparently lacked the cholecystokinin-like peptide showed extensive reinnervation of the host neostriatum. The cholecystokinin-positive fibres were found in a narrow zone immediately adjoining the graft. These results indicate that the dopaminergic reinnervation of the denervated neostriatum is preferentially carried out by the population of grafted mesencephalic dopamine neurones apparently lacking the cholecystokinin-like peptide. This suggests the presence of growth regulating mechanisms in the denervated neostriatum which selectively favour the ingrowth of fibres from the appropriate dopaminergic neuronal subset. The transplantation technique may therefore provide a powerful tool for the study of neurone-target interactions in the establishment of neuronal connections, and of the possible role of peptidergic coexistence in the development and organization of monoaminergic pathways and their innervation patterns.

Animals↗

Attempts to combine 2-deoxyglucose autoradiography and tyrosine hydroxylase immunohistochemistry.

The possibilities were analysed to combine the 2-deoxyglucose technique and indirect immunofluorescence histochemistry using tyrosine hydroxylase antiserum, with the aim to study functional activity in immunohistochemically characterized single neurons. Since the product measured with the 2-deoxyglucose method is water soluble and since immunohistochemistry requires that sections repeatedly run through aqueous media, the 2-deoxyglucose method was carried out before fixation and immunohistochemistry. The routine rapid thaw-mounting at + 60 degrees C of sections for 2-deoxyglucose autoradiography was found not to be compatible with immunohistochemistry. Instead a new mounting technique based on "gluing" the sections on to the object slide with a mixture of a standard mounting medium (Permount) and xylene was used to avoid diffusion at this stage. Two procedures were outlined, both starting with unfixed brains cut on a cryostat. In Method I autoradiographic sheet film was used. After autoradiographic exposure, the section was immersion-fixed in formalin, processed for immunohistochemistry, analysed and photographed in a fluorescence microscope and the results compared with the autoradiographic distribution patterns on the film. However, only the low resolution of the routine 2-deoxyglucose technique was obtained, which did not allow analysis of activity in single cells. In Method II, liquid emulsion applied by the loop technique was used. After exposure, autoradiographic developing and fixation, dehydration, mounting, analysis and photography of autoradiographs in the light microscope, the cover-slip was removed, the sections rehydrated and processed for indirect immunofluorescence histochemistry. With this procedure single autoradiographically labeled cells were observed, some of which contained tyrosine hydroxylase. Thus, with Method II it may in the future be possible to monitor functional activity in single immunohistochemically identified neuronal cell bodies. In order to obtain a useful and reliable method for this purpose, however, further extensive work with regard to, for example, quantification will be required.

Animals↗

Correction of adult penile curvature with a Nesbit operation.

Nesbit's technique of excising ellipses of tunica albuginea has been effective in correcting chordee in children. We have used this technique successfully in adults for the correction of 19 congenital and traumatic curvatures, as well as those resulting from stable Peyronie's disease. All patients retained potency and reported excellent correction of the deformities. We believe that Nesbit's operation is the procedure of choice for the correction of disabling adult penile curvature.

Adult↗

Should dopamine agonists be given early or late? A review of nine years experience with bromocriptine.

Experience with bromocriptine in 106 patients treated over nine years was reviewed. Most of the patients were already being treated with levodopa (combined with a peripheral decarboxylase inhibitor). These patients, after having initially achieved a good response to levodopa, were no longer responding satisfactorily. Most of the patients were also experiencing diurnal oscillations in performance: "wearing off" and "on-off" phenomena. In these patients previous attempts at changing the dose (increasing or decreasing) or changing the scheduling of levodopa had been unsuccessful. Bromocriptine was added to levodopa beginning at a dose of 5 mg/day, and each week was increased by another 5 mg/day. At a dose of bromocriptine of at least 25 mg/day, there was a decrease in disability in the majority of patients with a decrease in the severity of the diurnal oscillations in performance (especially "wearing off" phenomena). In most patients, the addition of bromocriptine resulted in an approximately 10% reduction in the dose of levodopa. The majority of patients sustained their improvement at least one year. In some patients improvement was sustained for up to five years. The therapeutic efficacy of bromocriptine was limited in many patients by the occurrence of adverse effects including mental changes, dyskinesias, orthostatic hypotension, and nausea. These adverse effects could often be minimized by reducing the dose of bromocriptine or levodopa. All adverse effects were reversible upon stopping the drug. We have found bromocriptine to be a valuable adjunct in the treatment of these patients.

Aged↗

A Ca2+-activated channel from Xenopus laevis oocyte membranes reconstituted into planar bilayers.

Plasma membrane fractions from Xenopus laevis oocytes were incorporated into planar lipid bilayers. We show the existence of numerous Ca2+-activated nonspecific channels that are more permeable to anions. These channels are activated by Ca2+ at micromolar concentration but not by Mg2+, Zn2+, or Mn2+, even at millimolar concentrations. Decreasing Ca2+ concentration to less than 1 microM decreases the time of channel opening until channels close completely in the absence of Ca2+ and in the presence of EGTA. I- and Br- are more permeable through this channel than Cl-. The time during which the channels remain open is also voltage-dependent, with the channels switching off at higher voltages in both polarities. Single-channel activity shows a conductance of 380 pS in 1 M NaCl and 1 mM CaCl2, with an average open lifetime of 1.5 s at 40 mV. Similar channels are found in different stages of oocyte maturation. These observations support the hypothesis that an increase in oocyte-free Ca2+ activates directly these channels, and the resultant Cl- efflux forms the ionic basis for the fertilization potential in X. laevis.

Animals↗

Calcium/phospholipid-dependent protein kinase (protein kinase C) phosphorylates and activates tyrosine hydroxylase.

Protein kinase C, purified to homogeneity, was found to phosphorylate and activate tyrosine hydroxylase that had been partially purified from pheochromocytoma PC 12 cells. These actions of protein kinase C required the presence of calcium and phospholipid. This phosphorylation of tyrosine hydroxylase reduced the Km for the cofactor 6-methyltetrahydropterine from 0.45 mM to 0.11 mM, increased the Ki for dopamine from 4.2 microM to 47.5 microM, and produced no change in the Km for tyrosine. Little or no change in apparent Vmax was observed. These kinetic changes are similar to those seen upon activation of tyrosine hydroxylase by cAMP-dependent protein kinase. Two-dimensional phosphopeptide maps of tyrosine hydroxylase were identical whether the phosphorylation was catalyzed by protein kinase C or by the catalytic subunit of cAMP-dependent protein kinase. Both protein kinases phosphorylated serine residues. The results suggest that protein kinase C and cAMP-dependent protein kinase phosphorylate the same site(s) on tyrosine hydroxylase and activate tyrosine hydroxylase by the same mechanism.

Animals↗

Solubilization and characterization of striatal dopamine receptors.

Dopamine receptor binding proteins were solubilized with the detergent 3-(3-cholamidopropyl) dimethylammonio-2-hydroxy-1-propanesulfonate (CHAPSO) from bovine and rat striatal membranes. The binding of the dopamine antagonist [3H]spiroperidol [( 3H]Spi) to the solubilized dopamine receptors was determined by the polyethyleneglycol method. The CHAPSO-solubilized dopamine receptor binding proteins remain in the supernatant fraction following centrifugation at 100,000 X g for 2 h. The CHAPSO-solubilized dopamine receptor proteins, as well as the prelabeled [3H]Spi-receptor protein complex, bind specifically to wheat germ agglutinin (WGA)-agarose columns, which is consistent with an identification as glycoproteins, HPLC analysis of the CHAPSO-solubilized, prelabeled [3H]Spi-receptor protein complex (CHAPSO preparation) reveals association with a high molecular weight form, indicating the formation of aggregates and/or micelles. Treatment of the WGA-agarose-bound [3H]Spi-receptor protein complex with digitonin (CHAPSO-digitonin preparation) results in dissociation of the high molecular weight form into lower molecular weight forms. The HPLC profile of the prelabeled [3H]Spi-receptor complex in the CHAPSO-digitonin preparation reveals two radioactive peaks. The major peak had a retention time of 16 min, corresponding to an apparent MW of 175,000, whereas the minor peak had a retention time of 21 min, corresponding to an apparent MW of 49,000. The CHAPSO-solubilized dopamine receptor binding proteins are sensitive to modulation by GTP, indicating that the association with the GTP binding component is preserved in the "soluble" state. The potencies of dopamine antagonists and agonists for inhibiting the binding of [3H]Spi to CHAPSO-solubilized dopamine receptor proteins are similar to those for membrane-bound proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Subcellular site of biosynthesis of the catecholamine biosynthetic enzymes in bovine adrenal medulla.

The subcellular site of biosynthesis of the catecholamine biosynthetic enzymes was examined. Free and membrane-bound polysomes were prepared from bovine adrenal medulla and mRNA was isolated from these polysomes. Both were active in directing cell-free translations. Immunoprecipitation of cell-free products with specific antisera localized the biosynthesis of the subunits of tyrosine hydroxylase (TH) (apparent Mr = 61,000) and of phenylethanolamine N-methyltransferase (PNMT) (apparent Mr = 32,000) on free polysomes, compared with biosynthesis of subunits of dopamine beta-hydroxylase (DBH) (apparent Mr = 67,000) on membrane-bound polysomes. Cross-reactivity between translation products was observed. Antibodies for DBH recognized a polypeptide with electrophoretic mobility identical to newly synthesized PNMT. However increasing concentrations of antibodies to DBH recognized at most 1/20 of the PNMT formed. The results of this study show the subcellular distribution of the catecholamine synthesizing enzymes is determined by their site of biosynthesis.

Adrenal Medulla↗

Coexistence of tyrosine hydroxylase-like and gamma-aminobutyric acid-like immunoreactivities in neurons of the arcuate nucleus.

The distribution of glutamic acid decarboxylase(GAD)- and tyrosine hydroxylase(TH)-like immunoreactivities in the hypothalamic arcuate nucleus of the rat was investigated using an indirect immunofluorescence technique. GAD-positive cell bodies were found in the arcuate nucleus, mainly clustered in its dorsomedial parts. A dense terminal plexus was observed in the lateral palisade zone of the median eminence. The apparent overlap of this distribution pattern with that for TH immunoreactivity was studied directly using an elution-restaining procedure. This revealed apparent coexistence of GAD- and TH-like immunoreactivities in a subpopulation of arcuate neurons. The relevance of this finding to the control of anterior pituitary secretion is discussed.

Animals↗

A new methodological approach for studying axonal transport: cytofluorometric scanning of nerves.

A new technique for studying axonal transport has been developed. The technique, which is based on histofluorescence techniques, enables the measurement of several different accumulated substances and parameters within a single nerve in relation to a nerve crush or local cooling. Any substance that can be made to fluoresce can be measured. The tissue is treated according to the formaldehyde-induced fluorescence method of Hillarp and Falck for visualization of monoamines, or according to the indirect immunofluorescence method. For immunofluorescence the nerve is cryostat-sectioned and various sections can be incubated with primary antisera against different antigens. After incubation and mounting the sections are placed in a cytofluorimeter (Leitz MPV II). They are passed under a measuring slit at a steady speed by a motor driven cross-table. The fluorescence intensity passing through the measuring slit is continuously registered by a recording unit with an integrator. This recorder produces a graphical nerve accumulation profile, and the area under the profile, relating to the fluorescence, is expressed in arbitrary units. This article presents data on the accumulation of noradrenaline, dopamine beta-hydroxylase, and tyrosine hydroxylase in crush-operated rat sciatic nerve. The time-course accumulations for noradrenaline (visualized by the Falck and Hillarp method) and dopamine beta-hydroxylase (visualized by immunofluorescence) demonstrated a striking similarity, which is to be expected since the two substances are stored in the same organelle. Tyrosine hydroxylase (visualized by immunofluorescence) showed a slower accumulation with time, but faster than would be expected had the enzyme been 100% soluble. Colchicine but not lumi-colchicine blocked the transport of noradrenaline organelles. With the new scanning technique we have the potential to study accumulation profiles of several different substances within a single nerve. Morphometric data, morphological observations, and photograph documentation of the same nerve section are also available.

Animals↗

An MMPI-based behavior descriptor/personality trait list.

Descriptive terms associated with elevated MMPI scales were abstracted from 10 MMPI reference works. Those corresponding to the 300-word Gough Adjective Check List were retained to construct a new behavior descriptor/personality trait list.

Journal Article↗

The luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6-Pro9-NEt]LHRH increased rather than lowered LH and alpha-subunit levels in a patient with an LH-secreting pituitary tumor.

Episodic secretion of LH, and the responses of serum LH, alpha-subunit, and testosterone concentrations to the acute administration of LHRH and the chronic administration of the LHRH agonist analog [D-Trp6-Pro9-NEt]LHRH (D-Trp6-Pro9) were evaluated in a 33-yr-old man previously reported to have an LH-secreting pituitary tumor unaccompanied by FSH hypersecretion. Basal serum LH and alpha-subunit concentrations were elevated [57 +/- 0.7 (SEM) mIU/ml (range, 45-71) and 26 ng/ml, respectively]. Frequent sampling revealed six LH secretory spikes over a 24-h period with increments above basal levels varying from 23-40% and interspike intervals ranging from 1.5-5 h. The concentrations of LH or alpha-subunit after iv administration of 150 micrograms LHRH did not increase above these intrinsic LH secretory increments (delta LH: 23%; delta alpha-subunit: 21%). The low basal serum FSH concentrations (3.5 mIU/ml) and elevated basal serum testosterone levels (1480 ng/dl) were unchanged after LHRH. Administration of clomiphene citrate produced no increase in serum LH, FSH, or testosterone concentrations. An attempt was made to decrease LH secretion in this patient using D-Trp6-Pro9. Administration of 200 micrograms daily sc of this LHRH analog for 21 days was associated with increases in serum LH and alpha-subunit concentrations. Mean serum LH and alpha-subunit levels for the 21 days of analog administration were 110 +/- 5.4 (SEM) mIU/ml (range, 70-170) and 64 +/- 3 (SEM) ng/ml (range, 32-84), respectively. During the 9-day period after discontinuance of the LHRH analog, levels of both serum LH and alpha-subunit declined precipitously and mean serum LH and alpha-subunit levels were 58 +/- 7 (SEM) mIU/ml (range, 18-90) and 22 +/- 3 (SEM) ng/ml (range, 12-44), respectively. We conclude that this patient's pituitary tumor has diminished responsiveness to acute LHRH administration and that the effect of chronic D-Trp6-Pro9 is stimulatory rather than inhibitory, as occurs after chronic administration of this analog to normal subjects. The blunted responsiveness to LHRH administration and the lack of response to clomiphene citrate suggest tumor autonomy. The presence of modest paradoxical responsiveness of serum LH and alpha-subunit concentrations during the course of daily D-Trp6-Pro9 administration suggests that central regulatory mechanisms, if present, are abnormal.

Adenoma↗

Long-term treatment with pergolide: decreased efficacy with time.

We studied the effect of pergolide (combined with levodopa) in 17 patients with Parkinson's disease, including 15 with "wearing off" or on-off phenomena, who had been taking pergolide for at least 2 years. Mean duration of the study was 27.8 months. All 17 patients improved initially, but the improvement later faded. Mean disability score, which decreased initially by 60% (significant), was decreased only by 20% after 2 years (not significant). Wearing off and on-off phenomena, which improved initially, became prominent again. Four patients lost all the improvement, nine patients lost much of the improvement, and four maintained much of the improvement. Mean dose of pergolide was 2.2 mg (range, 0.8 to 5.0 mg).

Aged↗