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Biomedical subjects

R Steinberg

Publications and source records attributed to R Steinberg.

At least 19 recordsLinked to original sources

Measurement of gamma-enolase release, a new method for selective quantification of neurotoxicity independently from glial lysis.

We have developed a sensitive enzymatic-immunoassay to quantify the level of gamma-enolase (a specific neuronal enzyme) which is released from cultured cells after exposure to various toxins. We show that this method can estimate selectively neuronal cell death without significantly interfering with glial cell death. Indeed, no gamma-enolase is released when glial cells are killed with free-radical producing agents. Experiments comparing the levels of neuronal cell death induced by NMDA or free-radical producing drugs, performed either by measuring gamma-enolase release or using the classical fluorescein diacetate method, yielded similar results. In addition to selectively follow neuronal death in a mixed population of neurons and glial cells, this method provides a way of determining the cell death kinetics from a single culture dish, since enolase can be measured on small samples taken from the culture medium. Finally, we propose these two methods as being complementary and useful neuronal and other cellular death indexes and also to understand the complex problem of glial influence on neuronal survival or death.

Animals

Calcium homeostasis, bone metabolism and safety aspects during long-term treatment with a GnRH agonist.

Thirty-five women with symptomatic fibroids were treated with monthly injections of 3.2 mg microcapsulated D-Trp-6-LHRH for 6 months. During treatment serum 17 beta-oestradiol levels decreased, falling to castration levels associated with a reduction in the volume of the fibroids. In 16 patients a complete calcium homeostasis and bone metabolism work-up was carried out during treatment and subsequently for a 6-month follow-up period. Bone mineral content (BMC) and Compton bone densitometry readings remained unchanged. There were significant increases in serum calcium phosphate and alkaline phosphatase concentrations. A slight although not significant increase was observed in osteocalcin and parathyroid hormone (PTH) serum levels. Serum 1,25(OH)2D3 values decreased significantly after 3 months of treatment. Urinary hydroxyproline/creatinine and calcium/creatinine ratios as well as 24-h urinary calcium values increased significantly during the treatment period but decreased rapidly to pretreatment values after 3 months in the follow-up period. The endocrine changes induced by the GnRH-agonist treatment were associated with reversible biochemical signs of increased bone turnover and no significant changes in bone mass, suggesting that the treatment can be administered safely for a period of 6 months in patients with oestrogen-dependent diseases.

Adult

The topography of microthrombi in ischemic brain infarct.

Following cerebral ischemia a tendency to increased coagulation can be detected. Vascular occlusion may develop either as a result of local thrombus formation or from emboli caused by circulating platelet aggregates. We studied the localization of microthrombi and their effects on tissue in double-hemisphere sections. Fresh brain infarcts showed a large number of microthrombi limited to the ischemic region. In more advanced infarcts they were found mainly at the border of the necrosis and diffusely distributed over both hemispheres. Older, subsiding infarcts showed only isolated microthrombi limited to the area of the necrosis. This indicates that great importance must be attached to microthrombi in infarct progression.

Aged

Music psychopathology. V. Objective features of instrumental performance and psychopathology.

Mental disease systematically impairs musical expression according to nosologic classification. This was demonstrated with a polarity profile of the instrumental performances of 60 inpatients and 14 controls matched for musical aptitude. Objective performance characteristics such as irregularities and playing faults were analyzed too. No meaningful correlation between these features and psychopathology resulted. This indicates that even in severe psychopathologic alterations performance features, which depend mainly on education and actual training, are not altered in a systematic manner, in contrast to expressive qualities.

Adult

Music psychopathology. VI. The course objective instrumental performance characteristics with psychiatric inpatients.

The impairment of musical expression due to mental disease is reversible with growing remission. This finding resulted from follow-up examinations of instrumental playings assessed by means of a polarity profile with 60 psychiatric inpatients and 14 controls. A follow-up comparison of objective performance characteristics as defined by careful analysis of the recordings did not reveal a meaningful variation. This is taken as a strong indication that even in severe psychopathologic alterations, learned motor patterns of music performance are fairly stable. A simple reduction in playing irregularities cannot explain the systematic influence of psychopathology on musical expression.

Adult

Brain dysfunction in psychiatric patients during music perception measured by EEG mapping: relation to motor dysfunction and influence of neuroleptic drugs.

We report here our findings on music perception obtained as a companion study to the investigation with 16-channel EEG mapping in psychiatric patients during motor activation, published recently elsewhere. We decided to add on a study of this functional circuit, since there is evidence that it is disturbed in various psychiatric patient groups (another "functio laesa"). Involved in the study were 23 male and 25 female schizophrenics, 11 male and 18 female non-endogenously depressed patients (not presently under medication, i.e. drug-naive or wash-out period from 1 week to 17 years), 26 male and 37 female endogenously depressed patients (medicated with tri- or tetracyclic antidepressants and/or benzodiazepines; no lithium), and 22 male and 17 female control subjects (i.e. n = 179). We compared resting conditions after a special relaxation procedure with three music perception tasks: (1) a standardised rumba rhythm generated by a keyboard and delivered binaurally by earphones, (2) the same as an arpeggio in D major, and (3) the same as an arpeggio with a tonic-subdominant-dominant cadence. Major results were obtained in the delta and alpha frequency bands, yielding signs of "diffuse hyperactivation", most prominent in schizophrenic males, and not observed to a similar extent in any other patient group or in normal controls. Interestingly, there were major sex differences, yielding a more diffuse EEG activation pattern in normal females than in males and thus possibly obscuring signs of brain function diffusion in female patients. Viewing our broader evidence of similar brain dysfunction when examining motor functional circuits, especially in schizophrenics, these findings provide further evidence of a brain disorganization with lack of laterality/diffusion which may be found in subgroups of these patients and not in other psychiatric disorders. In schizophrenic patients, these EEG signs of "diffuse hyperactivation" on simple motor and/or music stimulation were reduced to nearly normal by neuroleptic medication. The latter finding may contribute to possible clinical applications of EEG mapping, considering the EEG's unique suitability for long-term brain function monitoring. Other neuroimaging methods like SPECT and PET should be used for additional "external validation".

Adolescent

Music psychopathology. IV. The course of musical expression during music therapy with psychiatric inpatients.

The music therapeutic productions of 67 psychiatric inpatients were analyzed concerning a systematic variation in the course of therapy. The impairment of performance was not as regular as with customary music, nevertheless with growing remission it was reversible in all diagnostic subgroups. The change for the better of rhythmic and motor skills of endogenous-depressed patients was seen to the same extent as with traditional music. The polarity profile developed for the assessment of music proved meaningful in the characterization of music therapeutic utterances.

Adult

Calcium and potassium changes in extracellular microenvironment of cat cerebellar cortex.

1. Local stimulus-evoked changes in concentration of extracellular calcium ions, [Ca2+]0, and potassium ions, [K+[0, were measured in the cerebellar cortex of the cat using paired ion-selected micropipettes. 2. Repetitive stimulation of 30 s duration decreased [Ca2+]0 from a base line of 1.2 mM to as low as 0.8 mM and increased [K+]0 from 3 mM to as much as 8 mM. The magnitude of the changes was directly related to stimulus frequency. Laminar analysis showed that the greatest ion changes occurred at the level of maximum parallel fiber-Purkinje cell dendrite stimulation, but that the [Ca2+]0 changes were more localized than the [K+]0 changes. 3. Combining real-time current-source density measurement with [K+]0 determination and local manganese application, showed that the Mn blocked parallel fiber-Purkinje cell synaptic transmission, but that much of the [K+]0 changes persisted. Thus, a large part of the [K+]0 flux most probably originated in the parallel fibers. In contrast, [Ca2+]0 changes were abolished by the Mn, indicating that the decrease in this ion was probably associated with synaptic transmission or dendritic events. 4. In a few cases, spreading depression occurred in the cat cerebellar cortex. This could be accompanied by decreases in [Ca2+]0 to as low as 0.12 mM and increases in [K+]0 in excess of 48 mM. 5. These results show that significant changes in [Ca2+]0 and [K+]0 occur during cerebellar stimulation and indicate possible origins of the ion fluxes in terms of neuronal elements. This work also shows that the cerebellar cortex of the cat can support spreading depression. The present results, together with those of earlier studies on [Ca2+]0 and [K+]0 changes in the presence of aminopyridine in the cat cerebellum, suggest that synaptic or dendritic electroresponsive properties may play a role in the observed [Ca2+]0 and [K+]0 changes.

Animals

Red nucleus cell activity in awake cats during a placing reaction.

It is known that the discharges of the posterior red nucleus (RN) cells are modulated during locomation (Orlovsky, 1972). The aims of the present investigation were to look for a possible relationship between the unitary activity of RN cells and movements as well as postural reactions of the forelimbs. In the experimental arrangement used, the cat stood on four transducers which recorded to forces on each limb. The animal was restrained by a hammock supporting a part of the total body weight. A horizontally moving plate touched one forepaw and pushed it backwards until a placing mavement was induced. During the first part of the sequence, the mechanically stimulated limb was actively unloaded just prior to the placing movement, while the contralateral forelimb simultaneously presented a loading postural reaction. The results can be summarized and interpreted in the following way: 1. The RN cells exhibit large variations of discharge frequencies during phasic muscular activities linked to movement and to postural adjustments, but no correlations can be established between tonic cell activity and static postural forces exerted by the limb. 2. During the swing phase, the neuronal activity of some RN cells is maximal during flexion, while for others the maximum is during extension. 3. When there is a modification in frequency at the onset of the placing reaction relative to activity during the unloading reaction, the beginning of this change occurs after the onset of the movement as recorded by a potentiometer placed at the elbow joint. 4. The increases of frequency are higher during reciprocal muscle activation (during the movement) than during coactivation of antagonistic muscles (during the postural loading reaction). 5. During the loading reaction (with mostly extensor activation) the frequency of firing of those neurones discharging during the flexion phase. Thus the data may indicate that the RN is included in a feed-back loop which is linked not to muscle activities but rather to phasic spinal reflexes.

Action Potentials

Calcium modulation in brain extracellular microenvironment demonstrated with ion-selective micropipette.

Changes in extracellular Ca2+ concentration were directly measured in the rat cerebellum, using an ion-selective micropipette. Extracellular K+ was measured simultaneously with a second ion-selective micropipette. The potential reference barrels of the ion electrodes also provided fast field and slow potentials. During repetitive stimulation of the parallel fiber--Purkinje cell cerebellar circuit, extracellular Ca2+ fell to about 80% of base line concentration. During the spreading depression of Leão, extracellular Ca2+ fell to about 10% of base line; decreases of this magnitude also occurred during terminal anoxia. In all cases extracellular K+ increased substantially. These results show that extracellular Ca2+ is modulated during neuronal activity in the central nervous system and that under some conditions the Ca2+ change can be extreme. Given the well-established and antagonistic effects of reduce extracellular Ca2+ on axonal excitability and synaptic transmission, these results suggest that Ca2+ modulation in the brain cell microenvironment may be a significant parameter in the behavior of neuronal ensembles.

Animals

Osteoporosis in patients with fractured femoral neck in Jerusalem.

In an epidemiological survey on fractures of the femur in Jerusalem, the highest incidence occurred in Oriental males and the next highest in European females. In the same series of patients the frequency of senile osteoporosis was noted to be higher in the Oriental group (both male and female) as compared with that in the European group. Similarly in a randomly chosen sample of the population, osteoporosis in the Oriental sector was twice as high as in the European sector. Osteoporosis was also seen to be three to four times more common in each age group when the fracture series was compared with the randomly chosen sample. No evidence of osteomalacia was noted in these patients.

Activities of Daily Living

Effects of glutamate, aspartate, and two-presumed antagonists on feline rubrospinal neurones.

The actions of dicarboxyl amino acids (GLUT, ASP, DLH) and of presumed amino acid antagonists (GDEE, HA 966) were studied in rubrospinal neurones with microelectrophoretic techniques. ASP and GLUT depolarized reversibly the cell membrane and increased its conductance. ASP had slightly stronger actions than GLUT. DLH had strong depolarizing actions without a clearcut change in membrane conductance; this may be due to the fact that DLH effects do not involve synaptic receptors. A specific action as antagonists for GLUT could not be shown for GDEE or HA 966. HA 966 effects were often accompanied by apparent postsynaptic actions. GDEE antagonized DLH effects sometimes even stronger than GLUT effects. The effects of GLUT and ASP are in principal agreement with a function as excitatory transmitters. The demonstration of a role as transmitter substances in excitatory (e.g. corticorubral or interpositorubral) pathways, however, still awaits the specific pharmacological antagonist.

Animals

Effects of GABA, glycine, picrotoxin and bicuculline methochloride on rubrospinal neurones in cats.

A microelectrophoretic study was performed of the actions of GABA and glycine, and of their antagonists on rubrospinal neurones. GABA and glycine depressed antidromic and synaptic potentials, hyperpolarized the cell membrane and increased the membrane conductance. GABA was more effective than glycine. Corticorubral IPSPs and the GABA-induced membrane hyperpolarization could be reversed by intracellular application of hyperpolarizing currents. Picrotoxin and bicuculline methochloride antagonized inhibitory GABA actions and the corticorubral IPSP or the corresponding extracellular positive field potential. The results support the hypothesis that GABA is the transmitter of the corticorubral inhibition in the cat.

Aminobutyrates

Osteoporosis and fractures of the neck of the femur: some epidemiologic considerations.

The prevalence of osteoporosis in Jerusalem during the years 1967-71 was studied in a general population sample and in patients with fractures of the neck of the femur. Osteoporosis was determined by qualitative examination of lateral X-ray films of the lumbar spine. The prevalence of definite osteoporosis in a random population sample was 8.6%, and was higher in females (14.5%) than in males (2.9%). The prevalence of definite osteoporosis among 389 patients with fractures of the neck of the femur was 32.2%--37.8% in females and 17.4% in males. The results of this survey support the conclusion that osteoporosis plays an important role in the pathogenesis of fractures of the neck of the femur.

Female