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Biomedical subjects

E Melamed

Publications and source records attributed to E Melamed.

At least 109 records · Page 6Linked to original sources
PubMed1995

IL-3-LA production by mononuclear cells of patients with multiple sclerosis: effect of treatment with intravenous immunoglobulins.

IL-3-like activity (IL-3-LA) is a growth factor that stimulates stem cell maturation. We examined the production of IL-3-LA by peripheral blood mononuclear cells of 10 patients with relapsing-remitting multiple sclerosis (MS) following one year of treatment with intravenous immunoglobulins (IVIG). The results were compared with those obtained in 13 age- and sex-matched untreated patients with relapsing-remitting MS and in 14 healthy controls. IL-3-LA was assayed using the IL-3-dependent 32-D-cl-23 murine cell line. IL-3-LA production was 60% higher in untreated MS patients than in healthy controls (134 +/- 19 u/ml and 78.7 +/- 15.9 u/ml, respectively; p < 0.01), and lower in patients treated with IVIG than in untreated patients (101.4 +/- 4.9 u/ml; p < 0.02). IL-3-LA production also decreased after incubation of mononuclear cells with IVIG of both untreated MS patients and controls. This study indicates a possible beneficial effect of IVIG on the immunological status of MS patients.

Adolescent↗
PubMed1995

Does treatment with dopamine agonists affect utilization of exogenous levodopa in the parkinsonian striatum?

When the nigrostriatal projection is partially destroyed in Parkinson's disease, remaining neurons fire more rapidly and accelerate synthesis and release of dopamine (DA) from endogenous tyrosine and levodopa. It was suggested that such surviving hyperactive nigral neurons can also enhance the utilization of exogenous levodopa and generate adequate amounts of functional dopamine molecules to correct the reduced nigrostriatal neurotransmission. DA agonists stimulate presynaptic DA receptors and suppress nigrostriatal firing rates. Many parkinsonians are treated with a combination of DA agonists and levodopa. This could theoretically suppress both discharge of surviving dopaminergic neurons and their ability to convert exogenous levodopa to dopamine. To test this possibility, rats were injected i.p. with lisuride, bromocriptine or apomorphine alone or one hour after levodopa and decapitated one hour later. The DA agonists suppressed striatal DOPAC and DOPAC/DA ratios indicating attenuation of basic DA turnover. DA agonists given with levodopa did not decrease the levodopa-induced elevations in striatal levodopa, DA and DOPAC. Findings suggest that agonists do not affect entry of levodopa from the circulation into brain and do not alter striatal generation of DA from exogenous levodopa despite inhibition of nigrostriatal firing. Therefore, utilization of levodopa does not seem to depend on the state of discharge rates of nigral neurons and effect of levodopa and DA agonists in Parkinson's disease is additive.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons--a possible novel pathogenetic mechanism in Parkinson's disease.

We report that exposure of cultured, postmitotic chick-embryo sympathetic neurons, to physiological concentrations of dopamine (0.1-1 mM) for 24 h initiates a cellular death process characteristic of apoptosis (= programmed-cell-death, PCD). Dopamine caused marked morphological alterations, mainly axonal disintegration and severe shrinkage and condensation of cell bodies. Flow-cytometric analysis of propidium-iodide-stained cell nuclei revealed the characteristic apoptotic nuclear fragmentation: increase in nuclear granularity and emergence of a large, distinct population of nuclei with reduced DNA content (subdiploid, apoptotic peak). These alterations were similar to changes induced by nerve growth factor (NGF) deprivation, a model of sympathetic neuronal PCD. Alterations were inhibited by the anti-oxidative agent DTT. Inappropriate, dopamine-induced activation of PCD might have a role in nigral neuronal degeneration in Parkinson's disease.

Animals↗
PubMed1994

Can nimodipine affect progression of motor neuron disease? A double-blind pilot study.

Recently, there has been some evidence suggesting that exposure to neuroexcitotoxic amino acids, culminating in excessive neuronal calcium influx, may cause nerve cell destruction in motor neuron disease (MND). We therefore hypothesized that central calcium channel blockade with nimodipine might slow-down progression of MND. Two patients with sporadic MND were treated in a double-blind placebo controlled cross-over study with oral nimodipine (120 mg/day) for 5 months. Disease progression was assessed by repeated computerized measurements of isometric force from 20 muscle groups, and calculation of global force score. Global force deterioration slopes during the 5-month periods of nimodipine or placebo therapy were highly linear and almost identical. Nimodipine therefore does not seem to be effective in changing the course of MND. The observed remarkable linearity of disease course also confirms that cross-over methodology and serial measurements of muscle force are constructive tools in the clinical evaluation of novel therapeutic strategies for this devastating disease.

Administration, Oral↗
PubMed1994

Intravenous gammaglobulin treatment in multiple sclerosis and experimental autoimmune encephalomyelitis: delineation of usage and mode of action.

Multiple sclerosis (MS) is a central nervous system demyelinating disease of implicated autoimmune aetiology. The effect was evaluated of intravenous gammaglobulin (IVIg), a successful therapy in various autoimmune diseases, in relapsing-remitting MS patients treated for three years. IVIg treatment significantly reduced the number and severity of acute exacerbations and resulted in a lesser neurological disability. There were no significant short or long-term adverse effects to IVIg treatment. To clarify the putative therapeutic effects of IVIg, this treatment was examined in the animal model of experimental autoimmune encephalomyelitis (EAE) in the rat. IVIg suppressed active EAE in relation to disease severity and duration, despite the presence of T-cell reactivity to specific antigens, while the treatment had no effect on passive EAE induced by adoptive transfer of myelin basic protein specific CD4 + T-cells. It is concluded that IVIg treatment may be a promising treatment in relapsing-remitting MS as it can alter the natural course of the disease.

Adult↗
PubMed1994

Intravenous immunoglobulin treatment of experimental T cell-mediated autoimmune disease. Upregulation of T cell proliferation and downregulation of tumor necrosis factor alpha secretion.

It has been reported previously that intravenous administration of normal human immunoglobulins (IVIg) to human patients can suppress the clinical signs of certain autoimmune diseases. However, the mechanism(s) by which normal Ig interferes with the various disorders and the scheduling of treatment have been poorly delineated. To study these questions, we examined IVIg treatment of two experimentally induced T cell autoimmune diseases in rats: experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA). We now report that IVIg treatment (0.4 g/kg) inhibited the active induction of both EAE and AA, and that this treatment did not affect the acquisition of resistance to reinduction of EAE. The importance of the site of administration and schedule of treatment were studied in the AA model. Ig was effective when given intravenously, but not when administrated subcutaneously or intraperitoneally. IVIg treatment was effective when given daily from immunization to outbreak of disease; but it was also effective when given once at the time of immunization or once 2 wk after induction of AA, just at the clinical outbreak of disease. Administration of IVIg between immunization and outbreak of AA was less effective. Prevention of disease by IVIg occurred despite the presence of T cell reactivity to the specific antigens in the disease. In fact, IVIg administrated to naive rats activated T cell reactivity to some self-antigens. Nevertheless, IVIg treatment led to decreased production of the inflammatory cytokine TNF alpha. Thus, IVIg treatment may exert its therapeutic power not by inhibiting T cell recognition of self-antigens, but by inhibiting the biological consequences of T cell recognition.

Animals↗
PubMed1994

Machado-Joseph (Azorean) disease in a Yemenite Jewish family in Israel.

Machado-Joseph disease (MJD), an autosomal dominant, progressive, multisystem degeneration with cerebellar ataxia as the cardinal manifestation, usually affects individuals of Portuguese ancestry from the Azorean Islands. Cases have been reported in families from Japan, India, China, Brazil, and Australia. We report the first Israeli Jewish family with MJD, originating from a remote village near Ta'izz in Yemen.

Adult↗
PubMed1994

Body position does not affect the hemodynamic response to venous air embolism in dogs.

Current therapy for massive venous air embolism (VAE) includes the use of the left lateral recumbent (LLR) position. This recommendation is based on animal studies, conducted 50 yr ago, which looked primarily at survival. Little is known, however, about the concomitant hemodynamic response after VAE in various body positions. The purpose of this study was to investigate the hemodynamic and cardiovascular changes in various body positions after VAE. Twenty-two mechanically ventilated supine mongrel dogs received a venous air infusion of 2.5 mL/kg at a rate of 5 mL/s. One minute after the infusion, 100% oxygen ventilation was commenced and the body position of the dogs was changed to either the LLR (n = 6), the LLR with the head 10 degrees down (LLR-10 degrees; n = 6) or the right lateral recumbent (RLR; n = 5) position. Five dogs were maintained in the supine position (SUP; n = 5). One dog died in every group except in the SUP group, where all the dogs recovered. There were no significant differences among the various body positions in terms of heart rate, mean arterial pressure, pulmonary artery pressure, central venous pressure, left ventricular end-diastolic pressure, or cardiac output. The acute hemodynamic changes occurring during the first 5-15 min after VAE recovered to 80% of control within 60 min. Our data suggest that body repositioning does not influence the cardiovascular response to VAE. Specifically, our data do not support the recommendation of repositioning into the LLR position for the treatment of VAE.

Animals↗
PubMed1993

Detection and measurement of an endogenous clonidine-displacing substance in human cerebrospinal fluid.

Clonidine-displacing substance (CDS) is a novel endogenous ligand for clonidine receptors previously detected in bovine brain and human serum. We examined for the first time whether CDS can be detected and measured in human cerebrospinal fluid (CSF). Using the [3H]clonidine displacement assay, we found that CDS could be identified and quantified in each of the CSF samples obtained from 81 patients with various neurological disorders. Mean level of CDS in CSF was 4.66 units/ml. Exceedingly high levels were observed in the CSF of patients with neoplastic meningitis (mean, 36.75 units/ml) and stroke (mean, 19.5 units/ml) (P < 0.0001). No correlation was found between CDS levels in CSF and age, gender, CSF protein or number of cells. CDS levels in CSF were higher than those in the serum (P < 0.01). We conclude that CDS is present and can be measured in human CSF. High CDS levels in CSF from patients with leptomeningeal metastases may serve as a tumor marker for malignant infiltration of the meninges. Additional studies in stroke patients will determine whether this endogenous ligand plays a role in the pathogenesis of cerebral ischemia.

Adolescent↗
PubMed1993

Spastic paraparesis associated with human T-lymphotropic virus type I: a clinical, serological, and genomic study in Iranian-born Mashhadi Jews.

The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intrafamilial marriage among its members. A high risk of infection by human T-lymphotropic virus type I (HTLV-I) and of adult T-cell leukemia associated with such infection was found in this population. HTLV-I is also associated with a syndrome of progressive spastic paraparesis. We therefore evaluated the occurrence of HTLV-I infection and spastic paraparesis in Mashhadi-born Iranian Jews who immigrated to Israel. We examined 83 Mashhadi-born subjects (52 women, 31 men; mean age, 61 +/- 15.5 years) and 73 age-matched non-Mashhadi Iranian-born Jews. Blood samples were tested for HTLV-I antibodies by particle agglutination test. The polymerase chain reaction (PCR) was used to detect HTLV-I proviral DNA sequences from peripheral blood mononuclear cells. Fifteen Mashhadi-born Jews (18%) were both seropositive and PCR-positive for HTLV-I. Four HTLV-I-seronegative subjects were found to be positive for HTLV-I proviral DNA by PCR. Of the 19 HTLV-I-infected subjects (11 women, 8 men; mean age, 59 +/- 16 years), 13 (68%) had spastic paraparesis of varying severity. There were no signs of myelopathy in the Mashhadi-born subjects who were negative for HTLV-I proviral DNA by PCR. None of the non-Mashhadi Iranian Jews was seropositive or PCR-positive for HTLV-I proviral DNA, or had clinical signs of spastic paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Primary progressive freezing gait.

Freezing gait is an incapacitating symptom often observed in patients with Parkinson's disease. It has been less frequently described in association with multi-infarct state, multisystem atrophies, and normotensive hydrocephalus. In our movement disorder clinic, we have diagnosed (and followed up to 3 years; median, 16 months), 18 patients in whom progressive freezing gait was the sole neurological dysfunction. These 15 men and 3 women (aged 60-82 years; 74 +/- 6) were subjected to an extensive neurological workup that included clinical evaluation, videotaping for grading of gait disability, comprehensive blood and cerebrospinal fluid (CSF) analysis, and brain computed tomography (CT) and magnetic resonance imaging (MRI). Mean disease duration was 2.5 +/- 1.9 years (range, 0.5-6). Neurological examination disclosed freezing gait, often associated with varying degrees of postural instability. The degree of freezing gait ranged from sudden motor blocks only when confronted with obstacles to severe disability with total inability to start walking requiring a walker, massive assistance, or a wheelchair. However, patients could mimic gait movements with absolutely no freezing when seated or lying prone, and most of them could overcome arrests by the "walking-over-lines" maneuver. Otherwise, neurological examination was normal with no signs of bradykinesia, rigidity, or tremor. Blood chemistry and CSF analysis were normal. Brain CT and MRI were normal or showed mild cortical atrophy in 12 and putative lacunes in 6 patients. Therapy with levodopa or dopamine agonists was ineffective. During the follow-up period, a gradual progression of the freezing gait was observed. However, it remained unaccompanied by any other neurological findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Short-term beneficial effect of deprenyl monotherapy in early Parkinson's disease: a quantitative assessment.

It was recently shown that early treatment with deprenyl in patients with Parkinson's disease can delay the need for initiation of levodopa therapy. It was therefore suggested that deprenyl may slow down disease progression. Alternatively, the observed stabilization of clinical disability may merely reflect drug-induced symptomatic benefit. We therefore examined a possible short-term beneficial effect of deprenyl (10 mg/day) as the first and only drug in 15 consecutive de novo patients. Bradykinesia was quantitatively assessed by computerized analysis of isometric force/time curves of biceps and triceps bilaterally and by calculation of simple reaction time (RT) and maximal muscle contraction rate (MMCR). We also measured maximal muscle force, evaluated clinical status by the Unified Parkinson's Disease Rating Scale (UPDRS) motor score, and recorded patients' subjective reports. All tests were carried out before and at 1 and 2 months of treatment. Only one patient reported a beneficial effect. No significant changes in the UPDRS or score or muscle force were observed. In contrast, MMCR and RT improved at 1 month by an average of 12.1 and 7.2%, respectively (p < 0.01, paired t test). This improvement persisted after 2 months of treatment. Study shows that deprenyl monotherapy exerts a short-term beneficial effect in de novo parkinsonian patients. This effect, however, appears to be small, subclinical, and probably cannot account for the observed delay in the need to start levodopa therapy.

Aged↗