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D Jacobowitz

Publications and source records attributed to D Jacobowitz.

At least 19 recordsLinked to original sources
PubMed1998

Physiologic studies of spinal inhibitory circuits in patients with stiff-person syndrome.

OBJECTIVE: To test inhibitory spinal circuits in patients with stiff-person syndrome (SPS). BACKGROUND: Patients with SPS have fluctuating muscle stiffness and spasms, and most have antibodies against GABAergic neurons. We predicted they would also have abnormalities of spinal GABAergic circuits. DESIGN/METHODS: Physiologic methods using H-reflexes were used to test reciprocal inhibition in the forearm and thigh, vibration-induced inhibition of flexor carpi radialis and soleus H-reflexes, recurrent inhibition, and nonreciprocal (1b) inhibition of soleus H-reflexes. RESULTS: Vibration-induced inhibition of H-reflexes was diminished in eight of nine patients tested, but the presynaptic period of reciprocal inhibition was normal in most patients. Both circuits are presumed to involve presynaptic inhibition and GABAergic interneurons. Presumed glycinergic circuits, including the first period of reciprocal inhibition and nonreciprocal (1b) inhibition, showed occasional abnormalities. Recurrent inhibition was normal in all five patients tested. CONCLUSION: Differences between the two presumptive GABAergic circuits may indicate that not all populations of GABAergic neurons are uniformly affected in SPS. The involvement of presumptive glycinergic circuits in some patients could point to impairment of nonGABAergic neurons, unrecognized involvement of GABAergic neurons in these inhibitory circuits, or, more likely, alterations of supraspinal systems that exert descending control over spinal circuits.

Adult↗
PubMed1992

Poliovirus induces indoleamine-2,3-dioxygenase and quinolinic acid synthesis in macaque brain.

Accumulation of the neurotoxin quinolinic acid within the brain occurs in a broad spectrum of patients with inflammatory neurologic disease and may be of neuropathologic significance. The production of quinolinic acid was postulated to reflect local induction of indoleamine 2,3-dioxygenase by cytokines in reactive cells and inflammatory cell infiltrates within the central nervous system. To test this hypothesis, macaques received an intraspinal injection of poliovirus as a model of localized inflammatory neurologic disease. Seventeen days later, spinal cord indoleamine 2,3-dioxygenase activity and quinolinic acid concentrations in spinal cord and cerebrospinal fluid were both increased in proportion to the degree of inflammatory responses and neurologic damage in the spinal cord, as well as the severity of motor paralysis. The absolute concentrations of quinolinic acid achieved in spinal cord and cerebrospinal fluid exceeded levels reported to kill spinal cord neurons in vitro. Smaller increases in indoleamine 2,3-dioxygenase activity and quinolinic acid concentrations also occurred in parietal cortex, a poliovirus target area. In frontal cortex, which is not a target for poliovirus, indoleamine 2,3-dioxygenase was not affected. A monoclonal antibody to human indoleamine 2,3-dioxygenase was used to visualize indoleamine 2,3-dioxygenase predominantly in grey matter of poliovirus-infected spinal cord, in conjunction with local inflammatory lesions. Macrophage/monocytes in vitro synthesized [13C6]quinolinic acid from [13C6]L-tryptophan, particularly when stimulated by interferon-gamma. Spinal cord slices from poliovirus-inoculated macaques in vitro also converted [13C6]L-tryptophan to [13C6]quinolinic acid. We conclude that local synthesis of quinolinic acid from L-tryptophan within the central nervous system follows the induction of indoleamine-2,3-dioxygenase, particularly within macrophage/microglia. In view of this link between immune stimulation and the synthesis of neurotoxic amounts of quinolinic acid, we propose that attenuation of local inflammation, strategies to reduce the synthesis of neuroactive kynurenine pathway metabolites, or drugs that interfere with the neurotoxicity of quinolinic acid offer new approaches to therapy in inflammatory neurologic disease.

Animals↗
PubMed1983

S-100-mediated inhibition of brain protein phosphorylation.

The effects of the glial-specific, calcium-binding, S-100 protein on brain membrane and supernatant protein phosphorylation were assessed. S-100 concentrations as low as 5 micrograms/ml caused a marked inhibition of the phosphorylation of a soluble brain protein having a molecular weight of 73,000 daltons (73K). This protein was designated the S-100 protein-modulated phosphoprotein (SMP). Half-maximal inhibition of the phosphorylation of SMP by S-100 was obtained at concentrations of 12 micrograms/ml (0.57 microM). The inhibition of SMP phosphorylation by S-100 was calcium-dependent, with a calculated calcium Ka of 2.0 +/- 0.3 microM. SMP phosphorylation was also inhibited by calmodulin, but only partially and with a much lower potency. The inhibition of SMP phosphorylation by S-100 was not inhibited by fluphenazine, whereas the effect of calmodulin was. SMP was found in many brain areas, with the highest levels seen in the corpus callosum. Various peripheral tissues, such as kidney; liver; and pineal, pituitary, and adrenal glands, did not contain detectable SMP levels. At higher S-100 concentrations, greater than 10 micrograms/ml, the phosphorylation of several other soluble proteins was markedly inhibited. These proteins have molecular weights of 56K, 50K, and 47K. The phosphorylation of these proteins was enhanced by calmodulin. These data suggest that the S-100 protein may function to modulate the phosphorylation of brain proteins in a manner analogous to (although in a reciprocal fashion) that of calmodulin.

Animals↗
PubMed1981

Autonomic innervation of rabbit urinary bladder following estrogen administration.

The effects of estrogen administration on the autonomic innervation of the rabbit urinary bladder were studied. Immature female white rabbits were injected twice daily with estrogen (150 microgram./Kg.) for four consecutive days. Control animals received injections of vehicle alone. The adrenergic innervation was identified using the glyoxalic acid method of catecholamine histofluorescence. The cholinergic innervation was visualized utilizing specific acetylcholinesterase staining. Additionally, the effect of estrogen administration on the response of smooth muscle strips of urinary bladder to specific autonomic agonists was determined. Estrogen administration induced a moderate increase in the adrenergic innervation of the rabbit bladder detrusor, whereas no change could be observed in the cholinergic innervation. It should be noted, however, that whereas the adrenergic innervation in the bladder of the control animal was sparse, the cholinergic innervation in the bladder body was quite dense. Estrogen induced a marked increase in the response to alpha-adrenergic (methoxamine) and muscarinic cholinergic (bethanechol) agonists. No alterations were noted in the response to beta-adrenergic agonists (isoproterenol). These findings indicate that the urinary bladder responds as a target organ for estrogen-induced alterations in autonomic innervation.

Animals↗
PubMed1981

The ontogeny of the autonomic innervation and contractile response of the rabbit urinary bladder.

Although there has been considerable research on urinary bladder innervation, physiology and response to pharmacological agent, very little information is available concerning the ontogeny of bladder innervation and the contractile response to autonomic agents. The developmental aspects of urinary bladder innervation and function have been studied in the rabbit utilizing the following techniques: histochemical methodology to demonstrate autonomic innervation; in vitro responses to autonomic agents to demonstrate contractile responses; and ratio-ligand binding assays to determine specific receptor densities. The results of these studies can be summarized as follows: 1) at birth, the density of adrenergic fibers in the rabbit urinary bladder is very sparse, whereas there is a dense cholinergic innervation present. Over the first 6 weeks of postnatal development, there is a rapid progressive increase in the density of adrenergic fibers, whereas there is no significant change in the cholinergic innervation; 2) at birth, isolated strips of bladder respond poorly to methoxamine (alpha adrenergic agonist) and isoproterenol (beta-adrenergic agonist), but well to bethanechol (muscarinic cholinergic) and ATP (purinergic); 3) at birth, the density of adrenergic alpha and beta receptors is low; over the first 6 weeks of postnatal development, the density increases progressively to adult levels. The muscarinic receptor density is high at birth and does not change significantly over the first 6 weeks of postnatal development.

Animals↗
PubMed1979

Lack of evidence for adrenergic innervation of the external urethral sphincter.

Catecholamine histofluorescence studies of the external urethral sphincter in 11 normal dogs, 4 dogs treated with tranylcypromine and 4 humans have demonstrated that this striated muscle does not possess adrenergic innervation. This finding suggests that the sympathetic nervous system affects outlet resistance only through its influence on the smooth musculature of the bladder neck and urethra.

Animals↗
PubMed1976

Adrenergic innervation and stimulation of canine urethra.

Sympathetic nervous innervation of the canine urethra was studied using catecholamine histofluorescent straining and the in vitro muscle bath. Morphologically, adrenergic nerves were found terminating on the urethral smooth muscle. Pharmacologically, urethral strips responded like muscle strips from the bladder base to adrenergic stimulation. This evidence supports the concept that the sympathetic nervous system supplies and modulates the function of the smooth muscle stimulation of the rich periurethral vasculature nerve supply.

Animals↗
PubMed1976

NIH conference. Dopamine- -hydroxylase. Basic and clinical studies.

Dopamine-beta-hydroxylase, the enzyme responsible for conversion of dopamine to norepinephrine, is released along with catecholamines from the adrenal medulla and from sympathetic nerve endings. The properties and mechanisms of the enzyme's action are discussed and its distribution described. Dopamine-beta-hydroxylase is a valuable indicator of exocytosis as a mechanism for neurotransmitter release. The enzyme is present in plasma, but its levels vary widely between individuals. This variation seems to be related more to genetic factors than to sympathetic nerve activity. Abnormally high or low plasma levels are associated with several diseases. However, the relation of these levels to disease pathogenesis rather than to genetic determinants is unclear. Levels of the enzyme are elevated in patients with pheochromocytoma and decline after removal of the tumor. Dopamine-beta-hydroxylase levels seem to be normal in hypertensive patients. Inhibition of dopamine-beta-hydroxylase provides a useful pharmacologic approach to evaluating the role of norepinephrine in psychiatric disorders.

Adolescent↗
PubMed1975

Effect of long-term chemical sympathectomy on function of canine urinary tract.

Destruction of the adrenergic terminals in the ureter, bladder, and urethra was produced and maintained in 4 dogs for periods up to twelve months by biweekly intraperitoneal injections of 6-hydroxydopamine. The effects on urine transport, storage, and elimination were studied. The results are discussed in the light of current knowledge regarding the sympathetic innervation of these organs and its function.

Animals↗
PubMed1975

The acute and chronic effects of alcohol on the human immune system.

The immunologic status of 24 male patients admitted for acute alcoholic detoxification was evaluated by in vivo and in vitro parameters. In vivo reactivity, as measured by skin testing with a denovo antigen, dinitrochlorobenzene, as well as a recall antigen, tuberculin, was inact. However, both qualitative and quantitative defects were seen in vitro in the thymus-derived lymphocyte population. These defects were not seen in recovered alcoholics, that is, they appear reversible. The defects seen in the cell-mediated immunity of alcoholics may, in part, be responsible for the high incidence of head and neck cancer observed in this patient population.

Adult↗