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Biomedical subjects

Y Eshel

Publications and source records attributed to Y Eshel.

At least 37 records · Page 2Linked to original sources

Neurological and functional outcome in patients with supratentorial hemorrhages. A prospective study.

BACKGROUND AND PURPOSE: A prospective study was performed to evaluate neurological and functional outcome after spontaneous supratentorial bleeding. The aim of the study was to determine whether clinical or neuroradiological parameters could predict the outcome of these patients during the first hours of hospitalization. METHODS: Two hundred seventy-nine patients--52 with thalamic, 87 with putaminal, and 140 with lobar hemorrhages--were followed prospectively and examined on admission and at 2 weeks, 3 months, and 6 months after onset. The patients underwent clinical (according to the Glasgow Coma Scale) and neuroradiological examinations on admission and were scored clinically and functionally (according to Stroke Severity score and Barthel Index) on the follow-up periods. Risk factors and the correlation between findings on admission and the latest clinical and functional results were calculated with the chi 2 test, Pearson correlation test, and Student's t test. Multivariate analysis was calculated with the stepwise regression test. RESULTS: In all of the bleeding locations, lethal outcome was significantly correlated with size of the hematoma (P < .001) and Glasgow Coma Scale score on admission (P < .001). Intraventricular blood expansion was found to have a better prognosis in thalamic bleeding (P < .007) and a worse prognosis in lobar hemorrhage (P < .01). The functional outcome after 6 months was directly correlated with the size of the bleeding area in lobar and putaminal hemorrhages. No correlation was found in thalamic bleeding. A worse functional outcome was found in putaminocapsular bleeding (P = .004) and in patients with ischemic heart disease. A limited better recovery prognosis was found in patients with lobar hematoma in the temporal lobe (P = .052). CONCLUSIONS: The probability of lethal outcome can be calculated on admission in all patients with supratentorial bleeding and in correlation with the location and size of the bleeding area and level of consciousness. Intraventricular expansion of blood is a better prognostic factor in thalamic bleeding and a worse one in lobar hematoma. Functional outcome is correlated with size of the bleeding area and level of consciousness on admission in putaminal and lobar hemorrhages but has no correlation to thalamic hemorrhage.

Age Factors↗

Numerical calculation of the potential distribution due to dipole sources in a spherical model of the head.

A three-dimensional spherical model of the head was investigated numerically. The model consists of four conductive layers representing the scalp, the skull, the cerebrospinal fluid, and the cortex with a dipole current source. The potential created by the dipole was calculated using quasistatic formulation and a linear medium. The volume conduction equation was discretized by the finite volume method to ensure the conservation of fluxes and efficient solution method. The large set of algebraic equations for the electric potential was solved iteratively by the successive over relaxation method. The new formulation of the volume conduction problem was validated by comparing the numerical results with two analytical solutions. The first test-case considers a homogeneous spherical model with a dipole in the center. The potential on the outer surface, as well as within the volume conductor, was calculated and very good agreement was obtained with the analytical solution. In the second test-case, the scalp potential due to a radially oriented eccentric dipole in a four concentric spheres model was compared with an analytic solution. It was found that a grid of 90 x 90 x 90 volume elements yielded accurate results on the scalp surface with errors on the order of 1%. The present numerical model can be extended to general cases with any volume conductor shape or with any distribution or orientation of the current dipoles. Compared to other numerical methods, this approach offers enhanced accuracy for given computational resources (both in CPU time and memory). The gain might be more than one order of magnitude, allowing simulation with considerably larger meshes.

Body Surface Area↗

Calmodulin-binding peptides interfere with melanocyte-stimulating hormone receptor activity and stimulate adenosine 3',5'-monophosphate production in M2R mouse melanoma cells.

The MSH receptor belongs to a unique class of G-protein-coupled receptors, in which calcium ions control the binding affinity of MSH by a yet unknown mechanism. Possible involvement of a calcium-binding protein [e.g. calmodulin (CaM)] in the regulation of MSH receptor activity has been studied in the M2R mouse melanoma cell line. In this study, we tested the inhibitory effects of a group of calmodulin-binding peptides (CBPs) on MSH receptor activities in intact M2R cells and membrane preparations derived from them. We also report here on stimulatory effects of CBPs on cAMP production in M2R cells that could not be produced in other cell lines lacking MSH receptors. This group of CBPs includes synthetic peptides comprising the CaM-binding domains of Ca2+/CaM-dependent enzymes, cytotoxic venom peptides, and peptide hormones that have been reported to directly interact with CaM. The results show that CBPs, at micromolar concentrations, inhibit MSH binding and consequent adenylate cyclase stimulation in a specific and concentration-dependent manner, but have no effect on adenylate cyclase stimulation by prostaglandin E1. On the other hand, when MSH was omitted and forskolin (0.5-1 microM) was added instead, CBPs had the opposite effect on cAMP production, stimulating it in M2R cells, but not in other cell types tested. Thus, these peptides can be considered as antagonists of MSH receptor and partial agonists of M2R adenylate cyclase. In contrast to MSH, the stimulatory effects of CBPs were unaffected by EGTA, suggesting a Ca(2+)-independent action of these peptides. Using phospholipid vesicles and M2R cells, we recently showed that CBP activity in M2R cells may include direct partition into the lipid bilayer of the cell membrane, permitting interaction with hydrophobic lipid-inserted domains of components of the signal transducing machinery. Based on these findings, we suggest that the mechanism of action of CBPs in the M2R cells includes two major components: 1) interaction with the cell surface membrane and penetration into the lipid milieu, and 2) interaction with exposed or lipid-embedded protein epitopes intrinsically associated with the MSH-receptor system, thereby affecting the MSH receptor cascade.

Animals↗

Synthetic peptides corresponding to the calmodulin-binding domains of skeletal muscle myosin light chain kinase and human erythrocyte Ca2+ pump interact with and permeabilize liposomes and cell membranes.

Synthetic calmodulin-binding (CaM-binding) peptides (CBPs) representing CaM-binding domains of Ca2+/CaM-dependent enzymes have been reported to interfere with the activity of the melanocyte-stimulating hormone (MSH) receptor function in melanoma cells [Gerst, J. E., & Salomon, Y. (1988) J. Biol. Chem. 263, 7073-7078]. We postulated that membrane lipids may play an important role in the mode of action of CBPs on cells. We therefore tested the ability of CBPs to interact with membrane bilayers. Using artificial phospholipid vesicles, or M2R melanoma cells and cell membranes derived therefrom, as models, we report here that synthetic peptides representing the CaM-binding domains of skeletal muscle myosin light chain kinase (M5) and the human erythrocyte calcium pump (C28W), as well as other CBPs, interact with lipid bilayers and cell membranes. Significant interactions of CBPs with the lipid bilayer were detected in both model systems. M5 and C28W were found to partition into the lipid bilayer of melanoma cell membranes and soybean lecithin vesicles, and surface partition constants obtained (for the liposome model) were in the range 10(3)-10(4) M-1. In addition, C28W and its N-modified NBD derivative were found to inhibit [125I]iodo-[Nle4,D-Phe7]alpha MSH binding to cultured M2R melanoma cells. These and other CBPs were also found to induce the release of cations and calcein from liposomes, suggesting that the interaction of CBPs with the lipid bilayer increases membrane permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Signaling mechanisms controlled by melanocortins in melanoma, lacrimal, and brain astroglial cells.

Melanocortins appear to be involved as regulators in an ever growing number of physiological processes in cells and tissues of diverse functions. While such trends are apparent also in the case of other peptide hormones, it appears that melanocortin receptors can be regarded as unique among G-protein-linked receptors due to their special need for extracellular Ca2+ which may relate to some, yet undetermined selectivity of their actions. The physiological role that Ca2+ may be playing and the diverse signaling mechanisms regulated, as well as the nature of the cell-specific responses elicited in melanocortin-sensitive cells/tissues, have yet to be elucidated. Likewise, it will be of interest to establish the relationship of melanocortins to processes like growth and differentiation of cells, as well as to higher, more complex processes such as those regulated in the CNS.

Adenosine Triphosphate↗

Giant axonal neuropathy with predominant central nervous system manifestations.

The authors describe a 25-year-old woman with giant axonal neuropathy (GAN) and severe CNS involvement. She had been admitted to hospital with generalized seizures, and had gait disturbances followed by progressive mental deterioration since childhood. Neurological examination revealed mental retardation, scanning speech, cerebellar dysfunction, pyramidal signs, mainly in the lower extremities, and peripheral sensory neuropathy. Sensory nerve conduction velocity was decreased; brain CT and MRI showed diffuse demyelination. Sural nerve biopsy revealed characteristic signs of GAN. The patient's older sister had died at the age of 23, after having had similar neurological disturbances since childhood. This case illustrates an unfamiliar presentation of GAN, characterized by mild sensory neuropathy and serve CNS involvement, including seizures.

Adult↗

Weight gain, increased appetite, and excessive food intake induced by carbamazepine.

Four young patients who developed weight gain induced by carbamazepine therapy are described. The patients received the carbamazepine as anticonvulsant treatment, and soon after starting the drug, abruptly developed an increase in appetite with a concomitant increase in food intake. During a period of 2 months the patients' weights rose by between 7 and 15 kg. Dietary restriction during the carbamazepine treatment was ineffective in promoting weight loss, and loss of the excess weight was achieved only when the drug was discontinued. These patients demonstrate an as yet unpublished adverse effect of carbamazepine. In carbamazepine-induced weight gain, overeating and fat deposition must be taken into consideration as a differential diagnosis to the hitherto described water retention and edema.

Adolescent↗

Autosplenectomy complicating pneumococcal meningitis in an adult.

We present a rare complication of pneumococcal meningitis. A 56-year-old female patient with pneumococcal meningitis developed acute hyposplenism. Left-sided hypochondriacal pain accompanied by a marked thrombocytosis developed during the convalescent period. Abdominal radionuclide and computed tomographic scans demonstrated damage to the spleen. The findings were compatible with autosplenectomy.

Female↗

Alkaline phosphatase level in CSF in various brain tumors and pulmonary carcinomatous meningitis.

Twenty-six patients with various brain tumors or carcinomatous meningitis were examined for alkaline phosphatase (ALP) in the cerebrospinal fluid. ALP enzyme levels were compared with the respective levels in control groups of 75 patients with epilepsy, stroke, bacterial and viral meningitis and intervertebral disc prolapse. Extremely high ALP levels in CSF (9516 mu/l, 1425 mu/l, and 871 mu/l) were found in patients with pulmonary carcinomatous meningitis. Among all other patients with brain tumors, ALP levels in CSF were in the normal range. Examination of ALP in serum yielded normal results in all patients. In patients with pulmonary carcinomatous meningitis, the enzyme level in CSF was examined during various stages of radiotherapy and chemotherapy. Decreased ALP enzyme level was found during treatment followed by recurring rising levels a month after the treatment coinciding with clinical relapse. No correlation was found between the level of ALP enzyme and the biochemical and cellular content of the CSF during the various stages of treatment.

Adolescent↗

Glioblastoma multiforme with bone metastase and cauda equina syndrome.

Remote metastases, leptomeningeal dissemination and spreading of the tumor by infiltration are rare complications of glioblastoma multiforme. The existence of different forms of spreading simultaneously is very rare. We present a case of a young patient with glioblastoma multiforme who was operated and subsequently received radiation therapy and cytotoxic treatment. Eight months following the operation, the patient developed cauda equina syndrome. Bone metastases of vertebrae and ribs, and direct infiltration of the recurrent tumor mass into the ethmoidal and frontal sinuses were found. The described patient demonstrates a very rare combination of all forms of spreading metastases in glioblastoma multiforme. The infiltration of the tumor mass into the sinuses and the direct permeation of the meningeal and dural venous system and of the leptomeninges, may explain the mechanism of the development of distant metastases and leptomeningeal dissemination in glioblastoma multiforme.

Adult↗

Chloral hydrate in intractable status epilepticus.

Five adult patients were admitted to the neurological department in a state of status epilepticus. All were treated unsuccessfully with IV diazepam and diphenylhydantoin. Administration of sodium valporate or phenobarbital also was ineffective. However, after treatment with intrarectal chloral hydrate, all seizures ceased. The excellent effect of this drug was proved both clinically and electrodiagnostically. Discussed is the possibility of using chloral hydrate to treat patients with status epilepticus in whom conventional treatment has failed.

Administration, Rectal↗

Individualised instruction, congruent authority structure and student outcomes.

Measures of formal and informal authority structure were employed in order to assess academic and non-academic outcomes of individualised instruction. A sample of 386 fourth and fifth-grade elementary school children studying in nine individualised and 10 traditional classes was employed. Thus academic outcomes of either method of instruction were found to be contingent on the congruence between formal and informal authority structure: higher achievement scores were obtained when individualisation as school policy was accompanied by teacher sharing of authority with pupils at the informal classroom level. Achievement in less individualised classes was higher when teacher did not extend decision-making opportunities to pupils. Non-academic pupil outcomes were generally unrelated to either formal or informal authority structure. Similarities and differences between these results and former findings are discussed in light of cross-cultural differences in classroom individualisation.

Achievement↗

LDH isoenzymes in cerebrospinal fluid in various brain tumours.

This study examined the isoenzymatic pattern of LDH in the cerebrospinal fluid (CSF) as well as the ratio between the five fractions of LDH among patients with various brain tumours, carcinomatous meningitis and control groups. LDH 1/LDH 2 less than 1 was found significant for carcinomatous meningitis (p less than 0.001) and brain metastases (p less than 0.001). LDH 1/LDH 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases (p less than 0.05). No LDH 1/LDH 2 ratios smaller than 1 were found in the other groups. The LDH 1/LDH 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges. Examination of LDH 1/LDH 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage.

Biomarkers, Tumor↗

Cerebrospinal fluid lactate dehydrogenase levels in early stroke and transient ischemic attacks.

We examined the concentrations of lactate dehydrogenase in the cerebrospinal fluid of 25 patients with strokes and 15 patients with transient ischemic attacks less than or equal to 8 hours after the onset of the vascular event and in a control group of 21 patients. We found significantly higher concentrations in the stroke patients (40.9 +/- 14.5 units/l) than in the transient ischemic attack patients (11.8 +/- 2.9 units/l, p less than 0.001) and the controls (11.2 +/- 6.7 units/l, p less than 0.001). Among the stroke patients, we found a significantly higher lactate dehydrogenase concentration in those with cortical strokes (n = 12, 50 +/- 12.3 units/l) than in those with lacunar white matter infarcts (n = 5, 26.4 +/- 6.5 units/l; p less than 0.001) and those with basal ganglia infarcts (n = 8, 36.37 +/- 11.7 units/l; p less than 0.05). Our study offers a supplementary examination for diagnosing cortical or subcortical infarction during the early stage of the event, with the possibility of distinguishing precisely stroke from transient ischemic attack during the first hours after onset of the event.

Acute Disease↗

Characterization of the binding of alpha-bungarotoxin to bacterially expressed cholinergic binding sites.

Bacterially expressed cDNA fragments of the alpha-subunit of the nicotinic acetylcholine receptor previously have been shown to bind alpha-bungarotoxin (Gershoni, J. M. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 4318-4321). Here, a novel system has been developed in which totally synthetic alpha-bungarotoxin binding sites are expressed in Escherichia coli transformants. The amino acid sequences, alpha 184-200 and alpha 184-196 of the Torpedo californica alpha-subunit of the nicotinic acetylcholine receptor were expressed as trpE fusion proteins via the expression vector pATH2 and a method for the enrichment of these fusion proteins is described. Quantitative analysis of toxin binding to the recombinant binding sites demonstrates that they bind toxin with affinities of KD = 2.5 X 10(-7) and 4.7 X 10(-6) M, respectively. Furthermore, the pharmacological profile of alpha 184-200 qualitatively reflects that of the intact receptor. These data not only indicate that the area of alpha 184-200 is an essential element of the cholinergic binding site but that residues alpha 197-200 contribute a point of contact between the receptor and alpha-bungarotoxin.

Amino Acid Sequence↗