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Biomedical subjects

M Rubinstein

Publications and source records attributed to M Rubinstein.

At least 163 records · Page 9Linked to original sources

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↗

Different roles of D-1 and D-2 dopamine receptors involved in locomotor activity of supersensitive mice.

Simultaneous stimulation of both D-1 and D-2 receptors is necessary to reverse reserpine-induced akinesia in mice. The effect of supersensitivity on locomotor function was studied in mice after treatment with reserpine for five days. The response of these animals to a mixed D-1/D-2 agonist, pergolide, or to a presynaptic dopamine (DA) releaser, amphetamine, was increased 3-fold, indicating behavioural supersensitivity. Under these conditions, both selective D-1 and D-2 dopamine receptor agonist (SKF 38393 and LY 171555, respectively), given separately, induced locomotor activity. The D-1 antagonist, SCH 23390, inhibited the effect of both SKF 38393 and LY 171555, whereas the DA synthesis inhibitor, alpha-methyl-p-tyrosine (AMPT), and the D-2 antagonist, sulpiride, only abolished the effect of LY 171555. Moreover, AMPT increased the response to SKF 38393 by 80%. The amphetamine-mediated responses were abolished by SCH 23390 whereas sulpiride did not block them. Thus, stimulation of the D-1 receptor seems crucial in supersensitive animals. In another set of experiments, AMPT was administered to mice pretreated with reserpine for five days in order to fully deplete DA stores. Low doses of LY 171555 reduced the response of these animals to SKF 38393 by 60% whereas higher doses potentiated it. This bimodal effect of LY 171555 was blocked by sulpiride. Since amphetamine was unable to reverse the reserpine-induced akinesia in these mice, we can conclude that the inhibitory effect of LY 171555 is not related to presynaptic inhibition of DA release.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Two molecular forms of the human interferon-gamma receptor. Ligand binding, internalization, and down-regulation.

The receptors for human interferon-gamma (IFN-gamma) on peripheral blood monocytes and various cells of nonhematopoietic origin were thoroughly characterized and compared. The receptors of all cell types exhibited a similar affinity for IFN-gamma (Kd approximately 1 x 10(-10) M), and in all cases receptor-mediated endocytosis and ligand degradation were demonstrated. However, the receptors differed in their molecular weights (95,000 in HeLa cells and 140,000 in monocytes, assuming a 1:1 ligand to receptor ratio) as concluded from experiments of cross-linking to 125I-IFN-gamma. Lower molecular weight species were obtained as well, particularly in monocytes. Such species could represent either degradation products or subunit structures. The monocyte and HeLa receptor responded differently to an excess of ligand. A significant receptor down-regulation was observed when monocytes were incubated with an excess of 125I-IFN-gamma, whereas no such down-regulation was observed in HeLa cells or in normal fibroblasts. This differential response was observed both in the presence or in the absence of a protein synthesis inhibitor. The receptor on monocytes was found to be acid-labile whereas that on HeLa cells was resistant to acid treatment. These and additional experiments indicate that the monocyte receptor is inactivated following internalization, whereas the HeLa receptor retains its structure and recycles back to the cell surface. The difference in the properties and fate of these two receptor subtypes is probably related to the differential functions of IFN-gamma in various cell types.

Binding Sites↗

Postsynaptic bimodal effect of sulpiride on locomotor activity induced by pergolide in catecholamine-depleted mice.

In reserpinized (5 mg/kg, s.c.) mice treated with alpha-methyl-p-tyrosine (200 + 100 mg/kg, i.p.), increasing doses of the D-2 antagonist sulpiride had varying effects on locomotor activity induced by the mixed D-1/D-2 agonist pergolide (2 mg/kg, s.c.). Low doses of sulpiride (1 mg/kg, i.p.) significantly enhanced this activity whereas at higher doses (50 mg/kg) an inhibitory effect was observed. Amphetamine (3 mg/kg, i.p.) failed to reverse akinesia in this animal model, precluding the possibility of a presynaptically mediated phenomenon; in contrast, mice receiving reserpine alone showed a high degree of locomotor activity when challenged with amphetamine. The bimodal effect of sulpiride is thought to be mediated either by two different D-2 receptors located on the same cell or by the same receptor with different topographical localization on postsynaptic neurons mediating opposite functions.

Animals↗

The protective effect of interferon against natural killing activity is not mediated via the expression of class I MHC antigens.

Natural-killer cell mediated cytotoxicity (NK-CMC) is modulated by interferons both at the effector cell and at the target cell levels. Pretreatment of effector cells with interferon increases their cytotoxicity while pretreatment of target cells with interferons decreases their sensitivity to NK-CMC. Interferons are inducers of several genes including those of the major histocompatibility complex (MHC) and several earlier studies have established a circumstantial correlation between induction of class I MHC gene products and induction of resistance to NK-CMC. In the present study we demonstrate that interferon-alpha renders Daudi cells resistant to NK-CMC without inducing the surface expression of class I MHC antigens. Therefore we suggest that these two phenomena are independent responses to interferon treatment.

Cytotoxicity, Immunologic↗

Chronic labyrinthine ischemia.

The purpose of the present study was to describe the audiological and vestibular deficit in patients presumed to suffer from chronic impairment of the blood supply to the labyrinth. Thirty-nine subjects affected by various pathologies often impairing systemic blood circulation, which also presented labyrinthine damage of unclear origin, were evaluated for a possible relationship between these two conditions. At the time of this study 80 per cent of the subjects showed also a certain degree of increased blood viscosity. The most common finding in the group was slow and progressive bilateral sensorineural loss of hearing. In most of the subjects the labyrinthine damage began with high-tone loss which, in time, became a flat curve. Less common, but still found in many patients, was a fluctuation in threshold. Short periods of spontaneous subjective improvement in hearing were accompanied by a better result in the Pure Tone Audiogram and Speech Reception Threshold. The discrimination scores remained generally lower than expected. Vestibular examination revealed pathological results for all the subjects in at least some of the tests. The mild subjective complaints concerning equilibrium could be explained by a central nervous system compensation.

Aged↗

Single photon emission computed tomography in seizure disorders.

Fourteen children with various seizure disorders were studied using a cerebral blood flow tracer, 123I iodoamphetamine (0.05 mCi/kg), and single photon emission computed tomography (SPECT). In the five patients with radiological lesions, SPECT showed congruent or more extensive abnormalities. Five of the nine children with a normal scan on computed tomography had abnormal SPECT studies consisting of focal hypoperfusion, diffuse hemispheric hypoperfusion, multifocal and bilateral hypoperfusion, or focal hyperperfusion. A focal lesion seen on SPECT has been found in children with tonic-clonic seizures suggesting secondarily generalised seizures. Moreover the pattern seen on SPECT seemed to be related to the clinical status. An extensive impairment found on SPECT was associated with a poor evolution in terms of intellectual performance and seizure frequency. Conversely all children with a normal result on SPECT had less than two seizures per year and normal neurological and intellectual development.

Amphetamines↗

Cochlear hypoxia and the compound action potentials.

A relatively restricted area, including the ear, was perfused in guinea pigs with hypoxic blood having a pO2 of 10, 20, and 30 mm Hg, respectively. The changes induced to the cochlear action potentials were analyzed and the results compared with those obtained in a previous study in which the guinea pigs were rendered hypoxemic by ventilating them with air entrapped in a closed circuit from which the CO2 was continuously absorbed. The changes induced to the cochlear action potentials by both methods were very similar. However, while using the territorial model for inducing hypoxia, 75% of the animals showed a threshold shift at a blood pO2 of 20 mm Hg and with the general model all the animals showed a threshold shift at 25 mm Hg blood pO2. In other words, if the hypoxic condition affected the whole body, other factors such as a slight, but continuous tendency to acidosis with significant increase in blood lactic acid concentration could join the oxygen deficit in affecting cochlear function.

Action Potentials↗

The myeloid blood cell differentiation-inducing protein MGI-2A is interleukin-6.

The mouse myeloid blood cell differentiation-inducing protein, macrophage and granulocyte inducer, type 2A (MGI-2A), was purified, and the amino acid sequence of a CNBr cleavage peptide (22 residues) was determined. This amino acid sequence is identical to the sequence found in positions 73 to 94 of mouse interleukin-6 (IL-6). Recombinant mouse IL-6 protein induces differentiation of mouse myeloid leukemic cells that are induced to differentiation by MGI-2, and monoclonal antimouse-MGI-2 antibody, which neutralizes MGI-2, also completely neutralizes this IL-6-induced differentiation. These results show that the major type of mouse myeloid differentiation-inducing protein (MGI-2A) and IL-6 are very similar and most likely identical proteins. Recombinant human IL-6 (also called interferon-beta 2 or B-cell differentiation factor), which shows only a 41% similarity to mouse IL-6, has 11 identical amino acid residues out of the 22 in the mouse MGI-2A peptide and also induces differentiation of the same myeloid leukemic cells.

Amino Acid Sequence↗

Results after knee replacement with a posterior cruciate-substituting prosthesis.

From 1979 to 1984, eighty patients (119 knees) were arbitrarily selected for treatment with knee arthroplasty in which a posterior cruciate-substituting replacement was used. The average age of the forty-nine women and thirty-one men was 66.9 years (range, twenty-two to eighty-four years). Sixty-one right and fifty-eight left knees were operated on, and bilateral replacement was performed in thirty-nine of the eighty patients. The diagnosis was osteoarthritis in fifty-eight patients (eighty-eight knees), rheumatoid arthritis in fourteen patients (twenty-two knees), osteonecrosis in three patients (four knees), and traumatic arthritis secondary to a fracture of the tibia or femur in five patients (five knees). The average preoperative score on The Hospital for Special Surgery knee-rating scale was 47.5 points, and the average range of motion preoperatively was 88 degrees (range, 30 to 140 degrees). Of the 119 knees, eighty-seven had a varus alignment (maximum, 35 degrees) before knee replacement. After follow-up of two to eight years, the average score on The Hospital for Special Surgery scale was 90 points, and the average range of motion was 107 degrees. Of the 119 knees, 83 per cent were rated as excellent; 15 per cent, as good; none, as fair; and 2 per cent, as poor. Radiolucencies of one millimeter were present in 76 per cent of the knees; of two millimeters, in 7 per cent; and of three millimeters, in 3 per cent. No statistically significant correlation between radiolucencies and the clinical result was found. The results in knees of patients who had rheumatoid arthritis were not as good as those in knees of patients who had other diagnoses (F = 11.44). Our experience suggested that the posterior cruciate-substituting design provides more motion than do the cruciate-sacrificing surface-replacement designs, with no deleterious effects. The rate of infection (1.6 per cent) after these procedures, which were carried out in a standard operating theater with vertical airflow, was equivalent to that in other published series in which rooms with laminar airflow were used. Patients who had a bilateral procedure did as well as those who had a unilateral replacement, but they required approximately 3.5 more units of blood.

Adult↗

The human interferon-gamma receptor. Purification, characterization, and preparation of antibodies.

The receptor for human interferon-gamma (IFN-gamma) was purified from foreskin fibroblasts. Triton X-100 extracts obtained from either intact cells or membrane preparations were passed through an immobilized interferon-gamma column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of eluted fractions revealed a major band of Mr = 95,000 and minor bands of Mr = 80,000 and 60,000. Further purification was obtained by steric exclusion and by lectin chromatography. The purified receptor retained the ability to bind 125I-IFN-gamma with a Kd of 2.2 X 10(-10) M, a value close to that obtained with intact fibroblasts (5 X 10(-10) M). A complex of Mr = 105,000-125,000 was visualized by immunoprecipitation of 125I-IFN-gamma cross-linked to the purified receptor followed by SDS-PAGE and autoradiography. A similar complex was obtained when 125I-IFN-gamma was cross-linked to intact cells. Immunization of mice with the excised SDS-PAGE band of Mr = 95,000 elicited antibodies that blocked the antiviral activity of IFN-gamma and immunoprecipitated the cross-linked complex of 125I-IFN-gamma and its receptor.

Antibodies↗