An atypical responder to clozapine.
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Adult↗
Biomedical subjects
M Rubinstein
Publications and source records attributed to M Rubinstein.
Perilymphatic fistula in the guinea pig.
Clinical reports on perilymphatic fistulae (PLF) of the round window membrane (RWM) have shown different degrees of hearing loss. However, the hearing can also be entirely unaffected. Experimentally induced PLF of the RWM in animals showed results similar to those of the clinical reports, although some researchers have concluded that perforation of the RWM per se does not necessarily induce significant hearing loss. The purpose of the present study was to clarify if, and how, PLF of RWM in the guinea pig actually affects the auditory action potentials. During 1 h of observation following perforation of the RWM, the immediate and continuous effect of the PLF was evaluated. In more than 50% of the animals, different amounts of threshold shift were obtained. In another group of guinea pigs an attempt was made to clarify the findings by reducing the cerebrospinal fluid pressure before perforating the RWM.
Animals↗
Adaptive mechanisms of striatal D1 and D2 dopamine receptors in response to a prolonged reserpine treatment in mice.
Mice receiving reserpine (1 mg/kg/day) during 5 days develop behavioral supersensitivity. To study the possible molecular correlates of these adaptive changes we compared binding parameters of D1 and D2 receptors and adenylate cyclase activity in striata from normal and reserpinized mice. Saturation curves using [3H]SCH 23390 showed no changes in maximum binding capacity (Bmax) or Kd of striatal D1 receptors taken from control or 5 days reserpine-treated mice. However, [3H]spiperone saturation curves showed a 31% increase in D2 receptors Bmax with no changes in Kd. Dopamine competition of [3H]SCH 23390 and [3H]spiperone binding in mouse striatum was also performed. Analysis of data by LIGAND showed that dopamine recognizes two subpopulations for D1 and for D2 receptors. The proportion of receptors in the high affinity state (D1high and D2high) were increased in reserpine-treated animals. The addition of 100 microM GTP produced a complete conversion of D1high and D2high receptors into their low-affinity states in striata from control and reserpinized mice. Five days of reserpine treatment increased basal adenylate cyclase activity of mouse striatum in the presence of Mn++ or Mg++ ions. Concentration curves with dopamine, NaF or forskolin revealed shifts to the left and higher maximum responses without changes in EC50 values in striata from reserpinized mice. Thus, a prolonged reserpine treatment produces marked changes in D1 and D2 receptors increasing the proportion of high affinity state subpopulations and the total Bmax of D2 receptors. Also, dopamine function may be enhanced through an increment of the catalytic component of striatal adenylate cyclase.
Adenylyl Cyclases↗
Neurochemical and behavioral correlates of unilateral striatal acetylcholinesterase inhibition by fasciculin in rats.
Fasciculin 2 (FAS) an anticholinesterase peptide isolated from the venom of the Green mamba (Dendroaspis angusticeps) was injected into the right striatum of albino rats (1.5 micrograms total amount). The inhibition of acetylcholinesterase (AChE) activity was 86 and 60% 24 h and 7 days after FAS injection, respectively. The treatment with apomorphine (APO) (2 mg/kg s.c.) 24 h after FAS provoked a moderate circling towards the lesioned side that was reverted by atropine (30 mg/kg i.p.). The same dose of APO 7 days after FAS, provoked an inconstant contralateral circling. Neither dopamine nor serotonin nor their metabolites were significantly affected 24 h or 7 days after FAS injection. Radioligand binding assays of dopamine, muscarinic and benzodiazepine receptors only showed a decrease of the density of the muscarinic ones 7 days after FAS. These results are interpreted as showing that the changes provoked by FAS would be compensated but the system would remain in an unsteady state only demonstrable after pharmacological challenge. The chronic down-regulation of muscarinic receptors would compensate the increased cholinergic activity and would therefore block its behavioral expression.
Acetylcholinesterase↗
Soluble cytokine receptors are present in normal human urine.
Affinity chromatography of crude human urinary proteins on either human rIL-6, human rIFN-gamma, or anti-IFN-gamma-R mAb yielded the two respective soluble receptors in significant quantities. A single sequence of 30 amino acid residues was obtained by NH2-terminal microsequencing of the protein peak purified in tandem by affinity chromatography on an IL-6 column and reversed-phase HPLC. This sequence was identical to the predicted NH2-terminal sequence of IL-6-R as previously reported. Analysis of the eluted proteins from both IFN-gamma and anti-IFN-gamma-R columns by inhibition of solid phase RIA, ELISA, SDS-PAGE, and Western blotting proved the existence of soluble IFN-gamma-R in normal urine. Our finding, together with the already known presence of urinary TNF binding proteins and a soluble IL-2-R both in plasma and in urine, indicates that release of soluble cytokine receptors into body fluids is a general phenomenon that occurs under normal physiological conditions.
Amino Acid Sequence↗
A tumor necrosis factor-binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity.
Unfractionated preparations of the proteins of human urine provided protection against the in vitro cytocidal effect of tumor necrosis factor (TNF). In certain cells, the proteins decreased expression of the receptors for TNF in a temperature-dependent way. In all cells examined, the proteins were found to interfere also with the binding of both TNF and interleukin-1 when applied directly into the binding assays. That effect could be observed in the cold, suggesting that it was independent of cellular metabolism. A protein which protects cells against the cytotoxicity of TNF was purified from human urine by chromatography on CM-Sepharose followed by high performance liquid chromatography on Mono Q and Mono S columns and reversed phase high performance liquid chromatography. This protein is a very minor constituent of normal urine, with an apparent molecular weight of about 27,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. Homogeneity of the purified protein was confirmed by microsequence analysis which revealed a single N-terminal sequence: Asp-Ser-Val-Cys-Pro-. The protein protected cells from TNF toxicity at concentrations of a few nanograms per ml and interfered with the binding of both TNF-alpha and TNF-beta to cells, when applied simultaneously with the cytokines. However, unlike crude preparations of the urinary proteins, the purified protein did not induce in cells a decrease in ability to bind TNF nor did it interfere with the binding of interleukin-1 to its receptor. Direct, specific binding to the protein of TNF-alpha and, to a lesser extent, also TNF-beta, but not of interleukin-1 nor interferon-gamma could be demonstrated. It is suggested that this protein blocks the function of TNF by competing for TNF with the TNF receptor and not by interacting with the target cell.
Binding, Competitive↗
Analysis of multiscaling structure in diffusion-limited aggregation: A kinetic renormalization-group approach.
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Journal Article↗
Positive interaction between alpha-1 adrenergic and dopamine-2 receptors in locomotor activity of normo and supersensitive mice.
In normosensitive mice either the D1 antagonist SCH 23390 or the D2 antagonist sulpiride inhibited the reversion of reserpine-induced akinesia elicited by the mixed D1/D2 agonist pergolide. In mice rendered supersensitive by a five days' reserpine treatment, sulpiride did not prevent the pergolide-induced reversal of akinesia while SCH 23390 disclosed two subpopulations of mice. One population responded to pergolide with marked locomotor activity whereas in the other subpopulation this response was absent. However, all mice challenged with pergolide failed to reverse reserpine-akinesia after alpha-methyl-p-tyrosine (AMPT) pretreatment. The alpha 1/alpha 2 agonist clonidine restored the ability of pergolide to overcome reserpine akinesia in supersensitive mice pretreated with SCH 23390. Clonidine reversed the akinesia in supersensitive mice but in normal animals it did not. However, in these last conditions, the combined use of clonidine plus the D2 agonist LY 171555 was effective to induce locomotion. Neither AMPT nor SCH 23390 inhibited this response whereas the alpha-adrenergic antagonists prazosin and yohimbine did prevent it. The alpha 2 agonist B-HT 920 failed to induce locomotor responses when given together with LY 171555. The same occurred with the D1 agonist SKF 38393 when given together with clonidine. The combined use of SCH 23390 plus prazosin in chronic reserpinized mice prevented pergolide-induced locomotion. Adrenergic stimulation, acting on alpha 1 receptors, could be an alternative to D1 stimulation as a necessary factor to obtain D2-induced motor responses under normo and supersensitive conditions.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Validity of tympanometry in cases of confirmed otosclerosis.
The otoadmittence or impedance measurements are common procedures in the diagnosis of middle ear pathologies. The present study was undertaken for the purpose of studying the clinical validity of static admittance values in 42 confirmed otosclerotic ears. For both 220 Hz and 660 Hz probe tones only one third of the otosclrotic ears had low admittance values, as expected. The remainder showed admittance values in the normal or high ranges. No significant correlation was found between air bone gap (ABG) and the admittance values.
Acoustic Impedance Tests↗
Auditory and vestibular findings in Waardenburg's type II syndrome.
A group of 33 patients with the autosomal dominant form of Waardenburg Type II syndrome underwent hearing and vestibular examination. A bilateral, symmetrical, sensorineural hearing loss was found in 51 per cent of the tested subjects. The severity of hearing loss varied from mild to severe. Strong evidence indicated the possible progressive nature of the hearing loss. Concerning the frequency of vestibular findings, the study highlights the frequent divergence between cochlear and vestibular involvement.
Abnormalities, Multiple↗
Monoclonal antibodies to the human interferon-gamma receptor: blocking of the biological activities of interferon-gamma and purification of the receptor.
Monoclonal antibodies against the human interferon-gamma (IFN-gamma) receptor were developed by injecting mice with a preparation of receptor that was purified from solubilized placental membranes by ligand affinity chromatography. Three antibodies were identified by their ability to block the binding of 125I-labeled IFN-gamma to its receptor on HeLa cells at 4 degrees C. One of these antibodies blocked several biological activities of IFN-gamma, including its antiviral activity, its ability to induce HLA-DR surface antigens, and its ability to protect cells from NK cell-mediated cytotoxicity. This antibody exhibited higher binding capacity to cells at 37 degrees C and was significantly less displaceable by an excess of IFN-gamma as compared with the other two antibodies. Immunoaffinity chromatography of solubilized crude placental membrane preparation yielded a purified receptor that exhibited a molecular weight of 88,000. The purified receptor retained its ability to bind 125I-labeled IFN-gamma in solution.
Animals↗
Functional imaging of brain maturation in humans using iodine-123 iodoamphetamine and SPECT.
The application of regional cerebral blood flow (rCBF) study by means of lipophilic radiotracers and single photon emission computed (SPECT) devices in very young infants is hampered by the considerable changes of rCBF pattern as a result of the cerebral maturation process. In an attempt to determine the normal evolution of [123I]IMP SPECT pattern as a function of age, we retrospectively selected the studies of 30 babies with normal clinical examination, EEG and CT or ultrasound scans at time of SPECT. There was a marked predominance of the thalamic perfusion over cortical areas until the end of the second month. The distribution of regional cortical activity followed a strict sequence. The perfusion of both parietal and occipital areas was well-visualized around the 40th week of gestational age and thereafter rapidly rose, always, however, with a slight predominance of the parietal activity. At the opposite, frontal activity which remained scarcely recognizable up to the second month tremendously rose to present the adult-like pattern at the beginning of the second year. The rCBF changes described above are well in agreement with the behavioral evolution occurring during prime infancy.
Amphetamines↗
Biological activities of recombinant human IFN-beta 2/IL-6 (E. coli).
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Base Sequence↗
Mechanisms which take part in regulation of the response to tumor necrosis factor.
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Animals↗
Low frequency air-bone gap in Menière's disease without middle ear pathology. A preliminary report.
The audiograms of some patients suffering from Meniere's disease show an unexplained conductive component, or air-bone gap (ABG), predominantly in the low frequencies. Neither the history nor physical findings support poor eustachian tube function, ossicular chain abnormalities, chronic ear disease, physical trauma, or otosclerosis as a cause of this audiometric finding. In the present study, 40 patients diagnosed as suffering from classical Meniere's disease were evaluated audiometrically. Thirteen (32.5%) of these patients demonstrated a low frequency ABG. An otologic evaluation was performed on each patient who exhibited the abnormal finding, but no middle ear pathology was discovered. An otherwise unexplained low frequency ABG in patients with Meniere's disease suggests the possibility of an "inner ear" conductive hearing loss. This conductive component may result from endolymphatic hydrops or perilymphatic hypertension (i.e., an inner ear hyperpressure exerted against the medial surface of the stapedial footplate) rather than from middle ear pathology. "Inner ear" conductive hearing loss is thought to be caused by an increase in inner ear fluid volume (endolymphatic hydrops) and pressure (endolymphatic or perilymphatic hypertension), which dampens footplate mobility medially and which is directly related to a relative inner ear or labyrinthine hyperpressure. Since the footplate mobility is only dampened and not fixed, a stapedial reflex may still be elicited.
Adolescent↗
Brain single photon emission computed tomography in neonates.
This study was designed to rate the clinical value of [123I]iodoamphetamine (IMP) or [99mTc] hexamethyl propylene amine oxyme (HM-PAO) brain single photon emission computed tomography (SPECT) in neonates, especially in those likely to develop cerebral palsy. The results showed that SPECT abnormalities were congruent in most cases with structural lesions demonstrated by ultrasonography. However, mild bilateral ventricular dilatation and bilateral subependymal porencephalic cysts diagnosed by ultrasound were not associated with an abnormal SPECT finding. In contrast, some cortical periventricular and sylvian lesions and all the parasagittal lesions well visualized in SPECT studies were not diagnosed by ultrasound scans. In neonates with subependymal and/or intraventricular hemorrhage the existence of a parenchymal abnormality was only diagnosed by SPECT. These results indicate that [123I]IMP or [99mTc]HM-PAO brain SPECT shows a potential clinical value as the neurodevelopmental outcome is clearly related to the site, the extent, and the number of cerebral lesions. Long-term clinical follow-up is, however, mandatory in order to define which SPECT abnormality is associated with neurologic deficit.
Amphetamines↗
Recombinant interferon-beta 2 (interleukin-6) induces myeloid differentiation.
Human IFN-beta 2 cytokine produced in E. coli was purified to homogeneity by immunoaffinity and ion-exchange chromatography. The cytokine inhibits the growth of myeloleukemic M1 cells and induces their morphological and functional differentiation into macrophages. Differentiation was also observed in the histiocytic lymphoma U937 cells. The effect on U937 was synergized by IFN-gamma and under these conditions IFN-beta 2 produced the induction of (2'-5') oligo(A) synthetase typical to IFN action and to differentiation.
2',5'-Oligoadenylate Synthetase↗