Self-mutilation in Lesch-Nyhan disease is caused by dopaminergic denervation.
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Adolescent↗
Biomedical subjects
M Goldstein
Publications and source records attributed to M Goldstein.
Transformation of myeloma into Ph1-negative CML with plasma cell antigens.
We report a patient in whom Ph1-negative chronic myelogenous leukemia (CML) developed 15 years after the diagnosis of myeloma. Combined staining of morphologically myeloid elements in the peripheral blood for myeloid and plasmacytoid antigens revealed double-marker expression, suggesting that the two neoplasms arose from a common originator cell.
Antibodies, Monoclonal↗
Dual-ended, multifunction tools for microsurgery.
A new concept in microsurgical instrumentation is herein described and the rationale for its design presented in the context of surgical efficiency. This new concept employs bipolarity or dual-endedness as a means to enable the microsurgeon to have access to various instruments without the need to exchange tools. The elimination of instrument exchange has increased the speed with which a microsurgeon can perform a variety of procedures as well as decrease fatigue associated with continuous visual reaccommodation between the microscope and surrounding operating room. Following considerable modification through several prototypical stages and long periods of laboratory testing, these instruments boast ideal balance in the hands of the surgeon, and the capacity for modification by the user, allowing a variety of instrument combinations. Hence, personal preference can dictate the ultimate tool configuration, thereby allowing customization of the instruments to the procedure as well as the surgeon, by virtue of an interlocking mechanism between instrument components. The resulting economy of movement and reduced instrument handling engendered by the use of these instruments reduces operating time and often eliminates the need for a highly trained surgical assistant. These instruments can be fitted with a removable extension allowing unipolar use or extended instrument length. Simplicity of design makes these instruments conducive to standard cleaning and sterilization procedures.
Humans↗
Induction and reversal of dopamine dyskinesia in rat, cat, and monkey.
Abnormal involuntary movements (AIMs, stereotyped or dyskinetic movements) were induced with different dopamine mimetics in rat, cat, and monkey. In the rat only stereotyped movements were observed, whereas in the cat dopamine agonists (apomorphine) preferentially induced dyskinesia but dopamine/noradrenaline uptake inhibitors (d-amphetamine, nomifensine) induced predominantly stereotypes; L-dopa induced an equal, low, number of both kinds of movements in the cat. In the monkey with bilateral lesions of the nigrostriatal dopamine pathways the AIMs could be divided into type 1 dyskinesia (behavioral), type 2 dyskinesia (oral and psychomotor), and chorea. GABA agonists (progabide, muscimol) had a biphasic action on apomorphine stereotypes in the rat, slightly (10%-20%) augmenting these movements at low doses and antagonizing (greater than 50%) them at higher doses. As these latter doses of progabide also antagonize apomorphine-induced circling in rats with a unilateral lesion of the substantia nigra, it is likely that this action is exerted at or beyond the dopamine target cell. In cats the dyskinetic movements induced by apomorphine were abolished by progabide. In contrast, L-dopa-induced stereotypies were resistant to the antidyskinetic action of progabide, and at low doses of L-dopa an increased incidence of stereotypies was noted. In the monkey, the type 1 dyskinesia following L-dopa and piribedil were also relatively resistant to progabide administration, whereas the type 2 dyskinesia and chorea were abolished by progabide. These studies are parallel to and support the clinical observations that dyskinetic movements following a direct action at the dopamine receptor (tardive dyskinesia) may be reversed by progabide whereas those associated with dopamine neuron activity, perhaps together with noradrenergic activation (L-dopa dyskinesia), are resistant to the antidyskinetic action of progabide.
Animals↗
Immunohistochemical and biochemical study on the development of the noradrenaline- and adrenaline-storing cells of the adrenal medulla of the rat.
The pre- and postnatal development of the adrenal medulla was examined in the rat by immunohistochemistry and by assay of catecholamines. Immunohistochemistry involved the use of antibodies to noradrenaline (NA), adrenaline (A) and the biosynthesizing enzymes dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). Adrenal glands were obtained from animals from the 16th day of gestation to the 7th postnatal day at daily intervals, and at the 14th postnatal day, and from adult rats. Tissues were fixed in ice-cold, 4% paraformaldehyde, buffered at pH 7.3. Cryostat sections (7 microns) were stained with the indirect immunofluorescence technique. Adrenals from the same developmental stages were assayed for the presence of DA (dopamine), NA and A by ion-pair reversed-phase liquid chromatography with electrochemical detection. In adult adrenals the majority of the medullary cells (approximately 80%) were highly immunoreactive to A and moderately immunoreactive to NA. They also showed immunoreactivity to both DBH and PNMT, i.e., they are synthesizing and storing A. The remaining cell clusters were only stained by antibodies to DBH and NA (NA-synthesizing and -storing cells). These findings correlate well with the relative concentrations of A and NA as determined by assay. Three developmental phases could be distinguished. In the first phase, the 16th and 17th prenatal day, medullary cells were only immunoreactive to DBH and NA, and only very small amounts of A as compared to NA were found. During the second period, from the 18th prenatal day to 2 or 3 days after birth, all medullary cells were immunoreactive to DBH, NA, PNMT and A, and during this phase the adrenaline concentration increased daily and became the predominant amine on the 20th day of gestation. Adrenaline represented 75% of total catecholamine on the 1st to 3rd day after birth. The third phase started at the 2nd or 3rd postnatal day and was characterized by the presence of an increasing number of medullary cells solely immunoreactive to DBH and NA, hence synthesizing and storing NA. The remaining cells were immunoreactive to DBH, NA, PNMT and A. Postnatally, the relative concentration of A continued to rise reaching 79% by the 4th postnatal day. These results indicate that initially the adrenal medullary cells are synthesizing and storing almost exclusively NA.(ABSTRACT TRUNCATED AT 400 WORDS)
Adrenal Medulla↗
Neuropeptide Y (NPY)-like immunoreactivity in guinea pig uterus is reduced during pregnancy in parallel with noradrenergic nerves.
Neuropeptide Y (NPY) is a recently discovered neuropeptide with vasoconstrictor effects when given in vivo. It occurs in many sympathetic neurons, where it appears to coexist with noradrenaline (NA). It is wellknown that profound changes in the levels of uterine NA occur in many species during pregnancy. Therefore we have investigated the distribution of catecholamine neurons and NPY by immunohistochemistry in the pregnant and nonpregnant guinea pig uterus. In the virgin uterus NPY-like immunoreactivity was present in nerve fibres and terminals in the smooth muscle layers of the uterine horns and around blood vessels. The distribution of NPY fibres was very similar to that of noradrenergic nerves visualized with antibodies against the catecholamine synthesizing enzyme tyrosine hydroxylase (TH). In the pregnant uterus, NPY- and TH-like immunoreactivity disappeared almost completely. In the cervix, a slight decrease of immunoreactivity was observed, whereas in the ovaries no changes were noted between the pregnant and nonpregnant condition. The results indicate that NPY and catecholamines coexists in the adrenergic neurons of the guinea pig uterus, cervix and ovary and that they vary together in the myometrium during pregnancy. We suggest that NPY may be of functional importance for the pregnant uterus.
Adrenergic Fibers↗
Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons.
The effects of 6-hydroxydopamine (6-OHDA) and reserpine pretreatment on peripheral neuropeptide Y (NPY)- and noradrenaline (NA)-containing neurons were studied in guinea-pigs. Ten days after 6-OHDA pretreatment, a 60-80% reduction of the NA content was observed in the right atrium of the heart, stellate ganglion and spleen. The content of NPY-like immunoreactivity (LI) was reduced by about 50% in the heart, not changed in the spleen while it increased to 200% of control in the stellate ganglion. Immunohistochemistry showed a pronounced loss of NPY- and tyrosinehydroxylase (TH)-immunoreactive (IR) nerves in the heart but not in the spleen. Increased NPY-IR was seen in axons and cell bodies of the stellate ganglion. Reserpine pretreatment (thereshold dose 0.5 mg X kg-1) caused a dose- and time-dependent reduction of the content of NPY-LI in the heart. A maximal depletion of NPY-LI (about 80%) was observed 5 days after reserpine. Reserpine pretreatment also reduced the content of NPY-LI in the spleen, while no significant change was observed in the adrenal gland or vas deferens. The levels of NPY-LI increased in the stellate ganglion to about 180% of control 5 days after reserpine. Immunohistochemical analysis revealed an almost total loss of NPY-IR nerve fibres in the heart as well as around blood vessels in the lung and skeletal muscle. No detectable changes were observed in perivascular NPY-IR nerves in the spleen, vas deferens or kidney. TH-IR nerves remained unchanged after reserpine, thus indicating that the observed loss of NPY-IR nerves was due to a depletion of NPY and not a degeneration. No change in the levels of substance P-LI was observed in the right atrium 5 days after reserpine. NA was, in contrast to NPY, markedly depleted in all tissues investigated after reserpine treatment. The depletion of NA was more extensive, and occurred more rapidly and at much lower doses as compared to the effects on NPY-LI. Ligations of the sciatic nerve revealed that NPY-LI was transported axonally with a rapid rate (3 mm/h). Reserpine pretreatment significantly increased the amount of accumulated NPY-IR above the ligation, suggesting an increase in axonal transport. High performance liquid chromatography revealed that the NPY-LI consisted of two major peaks in the stellate ganglia, while only one peak closely corresponding to porcine NPY was seen in the right atrium. In conclusion, 6-OHDA pretreatment depletes NPY-LI in certain terminal regions and increases NPY-LI in ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Selective expression of high-affinity uptake of catecholamines by transiently catecholaminergic cells of the rat embryo: studies in vivo and in vitro.
Transient expression of catecholaminergic phenotypic traits is a widespread phenomenon during embryonic development in mammals, occurring in cells of the embryonic gut mesenchyme, in ventrolateral portions of the neural tube, cells of cranial sensory and dorsal root ganglia, and in the embryonic pancreas. In the current study the manifestation of the catecholamine (CA) phenotype in these populations has been further defined. Specifically, the existence of the high-affinity uptake process for CAs in these populations has been investigated. By combining the techniques of radioautography following accumulation of [3H]norepinephrine (3H-NE) and [3H]dopamine (3H-DA) with immunohistochemical detection of tyrosine hydroxylase (T-OH), it has been possible to demonstrate simultaneously CA accumulation by T-OH-positive gut cells. Uptake of 3H-NE was first detected in T-OH-positive cells of the gut on gestational day 12.5 (E12.5). By contrast, T-OH immunoreactivity was first detected on E11.5. By E13.5 virtually every T-OH-positive cell oral to the umbilical flexure was radioautographically labeled. Uptake at E13.5 displayed Michaelis-Menten saturation kinetics, had a Vmax of 35 fmole/gut/min, a Km of 1.45 microM, was blocked by desmethylimipramine (DMI), and by incubation at 4 degrees C. On subsequent gestational days, silver grains marking areas of amine concentration were found increasingly over T-OH-negative cells. A similar pattern of uptake was found in guts which had been grown in organotypic tissue culture for the purpose of eliminating extrinsic sympathetic innervation. T-OH-positive gut cells also accumulated 3H-DA. Concentration of 3H-DA was blocked by both benztropine and DMI suggesting that accumulation had properties common to both NE and DA systems. By contrast to cells of the gut, accumulation of CAs was not a property of transiently T-OH-positive cells in other locations. Therefore, specific, high-affinity uptake and retention of CAs is an additional property of transiently catecholaminergic gut cells. Appearance of CA synthetic enzymes precedes the appearance of the CA storage process in cells of the gut. Persistence of the uptake process after the loss of detectable T-OH suggests continued viability of the population. The absence of CA accumulation by other T-OH-positive cells suggests basic molecular differences among the various populations.
Animals↗
Skin testing in chymopapain anaphylaxis.
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Adult↗
Plasmacytoid blast crisis in B-cell chronic lymphocytic leukemia: effect of estradiol on growth and differentiation in vitro.
Evolution of a case of chronic lymphocytic leukemia (CLL) into blast crisis was found to be characterized by three unusual features (1) the phenotype of the emerging blast cells was that of pre-plasmacytoid cells as shown by plasma cell morphology and an immunological phenotype corresponding partially with CLL- or intermediate B-cells, partially with plasma cells (terminal transferase-, common acute lymphocytic leukemia antigen-, Ia+, surface immunoglobulin heavy chains-, surface kappa light chains+, intracytoplasmic immunoglobulin A+ and G+, BA-1+, polyclonal gammaglobulin production); (2) cytogenetic analysis of spontaneous metaphases revealed that in addition to the typical CLL abnormality, trisomy 12, in all of the cells, an additional translocation between chromosomes 14 and 17 was present in 40% with a presumptive breakpoint on chromosome 14 (q12-3) never described before (commonly q32) and (3) the progression of the disease was associated with a striking increase in the expression by the transformed cells of specific binding sites for estradiol (E2) due to an actual increase in total cellular receptor proteins and not to a change in receptor affinity for E2. The functional status of the steroid receptors was confirmed by nuclear transfer of the cytoplasmic hormone-receptor complex upon temperature activation. Since the rise in E2-receptor display paralleled a large increase in the proliferative activity of the cells as well as a change in their maturation status the question was raised as to whether the E2-receptor should be considered as a physiological marker of growth rate or of cellular differentiation. Exposure of the patient's blast cells to E2 in vitro resulted in cessation of cell growth following at least one mitosis after addition of the inducer as seen from the replacement of the large blasts by small CLL-like cells without definite signs of alteration of the differentiation status. This suggests the association of E2-receptor expression with control of growth rather than cell maturation.
Aged↗
Differential ontogeny of three putative catecholamine cell types in the postnatal rat retina.
The development of tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) in the rat retina was investigated using the indirect immunofluorescence technique. Two types of TH-positive cells were found. The first appeared at postnatal day 2, in the vitreal half of the inner nuclear layer (INL). Single fibres from these neurones, bifurcating in and innervating layer 3 of the inner plexiform layer (IPL) were seen at day 4. This first type of TH-positive cell was most numerous at day 15, but thereafter disappeared before adulthood. At day 5, a more intensely staining TH-immunoreactive neurone became visible, occupying a more proximal part of the INL, and projecting multiple fibres to layer 1 of the IPL. In contrast, PNMT-positive cells, in the vitreal half of the INL and in the ganglion cell layer (GCL), sending single varicose axons to layer 3 of the IPL, were first apparent only at day 10, achieving a disposition similar to that of the adult by days 15-16 postnatal. Analysis of adjacent sections stained with antibodies to TH and PNMT revealed that neither type of TH-positive neurone also contained PNMT-like immunoreactivity. It is concluded that although both of the rate-limiting enzymes of the catecholamine synthetic pathway are present in the developing rat retina, they occur in 3 mutually exclusive populations of neurones.
Animals↗
Substance K and substance P differentially modulate mesolimbic and mesocortical systems.
The newly discovered peptide substance K (SK) is an aliphatic tachykinin structurally related to the aromatic tachykinin substance P (SP). Immunohistochemical examination showed a close association between SK afferents and dopamine (DA) cell bodies. Examination of the possible role of SK in modulating midbrain DA systems revealed that SP, but not SK, is associated with the stress response of the mesocortical system. Ventral tegmental area injections of SK effected locomotor hyperactivity, a mesolimbic-mediated behavior. Ventral tegmental injections of SP, but not SK, activated DA metabolism in the prefrontal cortex, while SK injections altered DA metabolism in the nucleus accumbens, but not the cortical site. These data suggest that SK and SP may differentially modulate the mesolimbic and mesocortical systems.
Animals↗
Microspike approximator for vasovasostomy.
Stabilization of the ends of the vas deferens facilitates accurate microsurgical vasovasostomy. Commercially available approximating clamps are prone to slippage. We have modified our approximating clamps by folding stainless steel wire over the tips of the clamp blades and soldering them in place. The wire is trimmed to allow a short length to protrude into the grasping surface of the clamp, which provides microspikes that grasp securely only the adventitia of the vas deferens. We have used this clamp for more than 200 anastomoses without slippage. Its use often has obviated the necessity for inguinal extension of the scrotal incision. The microspike approximator provides a permanent solution to a vexing problem. This modification may be applied to approximating clamps of any design.
Humans↗
Aperistalsis of the vas deferens corrected with administration of ephedrine.
An infertile patient with azoospermia, normal spermatogenesis on a testis biopsy and no sperm seen on a post-ejaculate urinalysis underwent bilateral scrotal exploration. Normal anatomy was found at exploration and bilateral vasograms demonstrated the absence of obstruction. After subsequent therapy with ephedrine semen analysis showed a total sperm count of 72 million.
Adult↗
The use of pergolide and lisuride, two experimental dopamine agonists, in patients with advanced Parkinson disease.
Pergolide, an experimental dopamine agonist, was administered to 56 patients with advanced Parkinson disease who were no longer satisfactorily responding to levodopa, including 45 patients with diurnal oscillations in performance: "on-off" phenomena. Lisuride, an experimental dopamine agonist was administered to 63 patients with advanced Parkinson disease. Pergolide or lisuride, when added to levodopa, resulted in a significant decrease in disability in both the "on" and the "off" period, and an increase in the number of hours in which patients were "on". Forty-one of 56 patients (73%) improved on Pergolide. Thirty-seven of 63 patients (59%) improved on lisuride. Mean dose of pergolide was 2.5 mg. (range 0.2 to 10.0 mg.). Mean dose of lisuride was 2.6 mg. (range 0.2 to 5.0 mg.). Pergolide was discontinued in 18 patients because of adverse effects, including an organic confusional syndrome (six patients), dyskinesias (four patients) and cardiovascular abnormalities (three patients). Lisuride was discontinued in 26 patients because of adverse effects, including an organic confusional syndrome (15 patients), dyskinesias (five patients) and vasospasm (two patients). Pergolide was discontinued in nine patients and lisuride in 12 because of a lack of effect or a declining effect. Both drugs are equally useful in patients with advanced Parkinson disease.
Adult↗
Effects of lesions and ganglioside GM1 treatment on striatal polyamine levels and nigral DA neurons. A role of putrescine in the neurotropic activity of gangliosides.
The effects of a partial hemitransection at the meso-diencephalic level, with or without chronic ganglioside GMI treatment, have been evaluated on striatal polyamine levels, 7, 14 and 21 days after lesion, as well as on the ability of the polyamine synthesis inhibitor alpha-difluoromethylornithine (alpha-DFMO) to modulate the protective effects of chronic ganglioside GMI treatment against retrograde degeneration of the nigral dopamine (DA) nerve cell bodies (14 day time interval). The striatal polyamine levels were measured by high pressure liquid chromatography after dansylation of the polyamines. The nigral DA nerve cells were studied by means of tyrosine hydroxylase (TH) immunocytochemistry using the indirect immunoperoxidase technique. Quantitation was performed by means of morphometrical evaluation of the TH immunoreactive area of the substantia nigra. Seven days after partial hemitransection there is a marked increase (above 350%) in striatal putrescine levels, which is not modulated by chronic GMI treatment. This marked increase could, to a large extent, be counteracted by simultaneous treatment with alpha-DFMO, which blocks mainly the synthesis of putrescine. Twenty-one days after lesion chronic GMI treatment could produce an increase in striatal putrescine levels on the intact side and also after this time-interval prevent the reduction of striatal spermine levels. It was also found that simultaneous treatment with alpha-DFMO prevents the development of the protective action of chronic ganglioside GMI treatment against retrograde degeneration of the nigral DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Growth hormone releasing factor (GRF) and dopamine coexist in hypothalamic arcuate neurons.
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Animals↗
Cholecystokinin neuron systems and their interactions with the presynaptic features of the dopamine neuron systems. A morphometric and neurochemical analysis involving studies on the action of cholecystokinin-8 and cholecystokinin-58.
A unique role for CCK-58 compared to that for CCK-8 has been demonstrated in the modulation of central catecholaminergic mechanisms and neuroendocrine functions. It is of paramount importance to localize CCK-58 immunoreactivity within the brain in order to establish if separate CCK-58- and CCK-8-immunoreactive neuron systems exist. The two most significant actions of CCK-58 are a marked lowering of TSH secretion and a selective increase of DA turnover in DA-CCK co-existing synapses in the nucleus accumbens and tuberculum olfactorium.
Animals↗