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Biomedical subjects

Y Manor

Publications and source records attributed to Y Manor.

At least 19 recordsLinked to original sources

Synaptic depression mediates bistability in neuronal networks with recurrent inhibitory connectivity.

When depressing synapses are embedded in a circuit composed of a pacemaker neuron and a neuron with no autorhythmic properties, the network can show two modes of oscillation. In one mode the synapses are mostly depressed, and the oscillations are dominated by the properties of the oscillating neuron. In the other mode, the synapses recover from depression, and the oscillations are primarily controlled by the synapses. We demonstrate the two modes of oscillation in a hybrid circuit consisting of a biological pacemaker and a model neuron, reciprocally coupled via model depressing synapses. We show that across a wide range of parameter values this network shows robust bistability of the oscillation mode and that it is possible to switch the network from one mode to the other by injection of a brief current pulse in either neuron. The underlying mechanism for bistability may be present in many types of circuits with reciprocal connections and synaptic depression.

Animals↗

The influence of cytogenetic aberrations on gene replication in chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in humans, with the major cytogenetic aberrations of trisomy 12 and deletion of 13q14. This study examined the influence of these aberrations on general gene replication. The study group included three subgroups: (1) 15 CLL patients, (2) 4 CLL patients with trisomy 12, (3) 3 CLL patients with deletions in 13q14. Five healthy individuals served as a control group. Monocolor fluorescence in situ hybridization (FISH) with probes for c-myc, HER-2/neu, and p53 was applied to lymphocyte nuclei for the evaluation of replication timing. Asynchronous replication (SD) rate was significantly higher in all CLL patients (P < 0.01) when compared to the control group and was even higher in the group of CLL patients with trisomy 12 and 13q14 deletion (P < 0.01). The asynchrony rate was significantly higher in cells with trisomy 12 for all three probes analyzed, compared to "healthy" cells in the same patients (P < 0.001). To conclude, in CLL patients with a chromosomal aberration such as trisomy 12 and 13q14 deletion we were able to demonstrate a high rate of asynchrony of replication. The high correlation between cells with trisomy 12 and SD pattern could reflect direct influence of the aberration on gene replication and cell cycle control.

Aged↗

Dental extractions in patients maintained on oral anticoagulant therapy: comparison of INR value with occurrence of postoperative bleeding.

The purpose of this study was to evaluate the incidence of postoperative bleeding in patients treated with oral anticoagulant medication who underwent dental extractions without interruption of the treatment and to analyze the incidence of postoperative bleeding according to the International Normalized Ratio (INR) value. The 249 patients who underwent 543 dental extractions were divided into five groups: Group 1 with INRs of 1.5-1.99, Group 2 with INRs of 2-2.49, Group 3 with INRs of 2.5-2.99, Group 4 with INRs of 3-3.49 and Group 5 with INRs>3.5. The INR was measured on the day of the procedure. Local haemostasis was carried out with gelatin sponge and multiple silk sutures. Of the 249 patients, 30 presented with postoperative bleeding (12%): Group 1, three patients presented with bleeding (5%), Group 2, 10 patients (12.8%), Group 3, nine patients (15.2%), Group 4, five patients (16.6%) and Group 5, three patients (13%). The incidence of postoperative bleeding was not significantly different among the five groups. The value of the INR at the therapeutic dose did not significantly influence the incidence of postoperative bleeding. Thus, dental extractions can be performed without modification of oral anticoagulant treatment. Local haemostasis with gelatin sponge and sutures appears to be sufficient to prevent postoperative bleeding.

Administration, Oral↗

Secondary wastewater disposal for crop irrigation with minimal risks.

A critical objective for any wastewater reuse program is to close the gap between supply of and demand for water and to minimize health and environmental hazards. Thus, the effects of treated effluent on crops, soils and community health must be considered carefully. When applying wastewater to soil-plant systems, it is to be noted that the passage of water through the soil reduces considerably the number of microorganisms carried out by the reclaimed wastewater. Nevertheless, there is a need to study the real rate of organism decay subject to water quality, soil and vegetable characteristics, and irrigation method. The aim of this work is to determine the fate of the fecal coliforms, coliphages F+ and CN13, and helminth eggs survival during the application of reclaimed wastewater in a vineyard orchard near the City of Arad (Israel) via onsurface and subsurface drip irrigation systems. Wastewater obtained from a stabilization pond, and soil samples were tested and an important decrease of microorganisms was reached in both cases, with the better values obtained with the sub-surface drip irrigation system.

Agriculture↗

Multiple myeloma: monoallelic deletions of the tumor suppressor genes TP53 and RB1 in long-term follow-up.

Recently, a working-model of a stepwise malignant transformation in the molecular pathogenesis of multiple myeloma (MM) was proposed, involving the tumor suppressor gene TP53 and retinoblastoma gene (RB1) as prominent components of cell cycle control. To further define the role of TP53 and RB1 in disease progression, we retrospectively analyzed by fluorescence in situ hybridization (FISH) cytological material from 16 patients who underwent sequential bone marrow biopsies during the course of their disease. For TP53, no deletions were detected at presentation or during follow-up. It is possible that the patients reported here represent a subset with relatively long survival, and therefore did not demonstrate the TP53 deletions that had been reported in patients with a very poor prognosis. For RB1, monoallelic deletion was demonstrated in nine patients. In each case, the deletion appeared already in the first biopsy analyzed. The presence of a deletion did not affect the rate of tumor progression or the length of follow-up, and thus prognosis. Monoallelic deletions of RB1 appear to be a frequent and early event in the pathogenesis of MM, without obvious relevance for disease progression.

Aged↗

The role of short-term synaptic dynamics in motor control.

During the past few years, much attention has been given to the role of short-term synaptic plasticity, in particular depression and facilitation, in sculpting network activity. A recent study shows that synaptic depression in rhythmic motor networks could switch the control of network frequency from intrinsic neuronal properties to the synaptic dynamics. Short-term synaptic plasticity is also involved in the stabilization and reconfiguration of motor circuits and in the initiation, maintenance and modulation of motor programs.

Animals↗

Neurological complications of essential thrombocytosis (ET).

OBJECTIVE: To evaluate the prevalence of neurological abnormalities in patients with ET and attempt to identify risk factors for neurological complications. METHOD: Ninety-five patient charts were reviewed from January 1983-July 1999. Seventy patients fulfilled the Polycythemia Vera Study Group criteria for diagnosing ET. RESULTS: Eighteen patients (25.7%) had episodes of neurological impairment, 52 (74.3%) had none. Neurological features-- occlusive cerebrovascular event-9; chronic headache-3 and dizziness-3, mononeuritis multiplex, sinus vein thrombosis and epilepsy-1 each. The interval between diagnosis of ET and occurrence of neurological events ranged from time of presentation (10 patients) to 13 years (1 patient) with a high predominance of females, 88.8% and 55%, respectively. CONCLUSIONS: Neurological complications occurred at presentation or during follow-up in approximately 25% of patients with ET. Our observation suggests that further investigation focusing on the possible mechanisms for neurological deficits in females with ET should be considered.

Adult↗

Risk factors contributing to symptomatic plate removal in maxillofacial trauma patients.

This study analyzed the fate of plates used to correct maxillofacial injuries and defined risk factors that eventually resulted in plate removal. The outpatient clinic files of 108 patients treated with rigid internal fixation after maxillofacial trauma were reviewed. Study variables included age, sex, trauma circumstances, diagnosis, type of fracture, approach to the facial skeleton, presence of teeth in the line of fracture, plate material, site of plates, and reasons for plate removal. Of 204 plates used for fixation, 44 plates (22 percent) were removed. When all factors were considered together, only fracture diagnosis (mandibular body and angle) and plate location (mandibular body and angle) were statistically significant. Only when each factor was considered separately, the approach to the facial skeleton (intraoral) and the type of fracture (comminuted and compound fractures) were statistically associated with plate removal. Selection of favorable plate location, the extraoral approach, and vigilant infection control may reduce plate removal in patients with maxillofacial injuries. Special attention should be given to compound and comminuted fractures of the mandibular body and angle.

Adolescent↗

Molecular and antigenic characterization of a highly evolved derivative of the type 2 oral poliovaccine strain isolated from sewage in Israel.

An unusual, highly diverged derivative of the Sabin type 2 oral poliovaccine (OPV) strain was recovered from environmental samples during routine screening for wild polioviruses. Virus was cultivated in L20B cells and then passaged on BGM cells at 40 degrees C (RCT [reproductive capacity at supraoptimal temperature]-positive marker) to select against most OPV strains. All but 1 of 25 RCT-positive OPV-derived environmental isolates were antigenically and genetically (>99.5% VP1 sequence match) similar to the respective Sabin strains. However, isolate PV2/4568-1/ISR98 (referred to below as 4568-1) escaped neutralization with Sabin 2-specific monoclonal antibodies and cross-adsorbed sera, and had multiple nucleotide substitutions (220 of 2,646; 8.3%) in the P1 capsid region. Fourteen of the 44 associated amino acid substitutions in the capsid mapped to neutralizing antigenic sites. Neutralizing titers in the sera of 50 Israeli children 15 years old were significantly lower to 4568-1 (geometric mean titer [GMT], 47) than to Sabin 2 (GMT, 162) or to the prototype wild strain, PV2/MEF-1/EGY42 (GMT, 108). Two key attenuating sites had also reverted in 4568-1 (A(481) to G in the 5' untranslated region and the VP1 amino acid I(143) to T), and the isolate was highly neurovirulent for transgenic mice expressing the poliovirus receptor (PVR-Tg21 mice). The extensive genetic divergence of 4568-1 from the parental Sabin 2 strain suggested that the virus had replicated in one or more people for approximately 6 years. The presence in the environment of a highly evolved, neurovirulent OPV-derived poliovirus in the absence of polio cases has important implications for strategies for the cessation of immunization with OPV following global polio eradication.

5' Untranslated Regions↗

Risk factors and management of patients with upper limb deep vein thrombosis.

STUDY OBJECTIVES: To determine the prevalence of endogenous and exogenous risk factors for venous thrombosis in patients with upper limb deep vein thrombosis (DVT), and to evaluate the risk of clinically detectable pulmonary embolus, recurrent DVT, and postphlebitic symptoms in these patients. DESIGN: A combined prospective and retrospective descriptive analysis of a cohort of patients with upper limb DVT compared with age- and sex-matched patients with lower limb DVT. SETTING: Internal medicine departments, and hematology and vascular surgery outpatient clinics at a tertiary-care university hospital. PATIENTS: Consecutive patients with "spontaneous" upper limb DVT diagnosed between 1989 and 1997 were studied. Twenty age- and sex-matched patients with lower limb DVT admitted to the hospital via the emergency department served as control patients. RESULTS: Eighteen patients with upper limb DVT were studied. An endogenous risk factor (thrombophilia) was present in 11 of 18 patients vs 8 of 20 control patients (p = not significant). In the upper limb group, nine patients had activated protein C resistance, four patients had anticardiolipin antibodies, and two patients had both forms of thrombophilia. Furthermore, 14 of the upper limb DVT patients were found to have an exogenous risk factor for thrombosis compared with 7 of the patients with lower limb DVT (p = 0.01), and 66.6% of patients with upper limb DVT had both an exogenous and an endogenous risk factor for thrombosis vs 15% of patients with lower limb DVT (p < 0.002). No clinically detectable pulmonary emboli occurred among the upper limb DVT patients. Three patients have minor postphlebitic symptoms. Two patients experienced recurrent DVT. CONCLUSION: In the majority of patients with upper limb DVT that we studied in this relatively small study, exogenous (environmental) or endogenous risk factors for venous thrombosis, or a combination of both, were found. Furthermore, in our patients, these thromboses had a low propensity to cause clinically significant pulmonary embolus and did not cause significant postphlebitic symptoms. Finally, we suggest that anticoagulant therapy for these thromboses may be adequate and that thrombolytic agents and surgical intervention are not routinely indicated.

Activated Protein C Resistance↗

Primary antiphospholipid syndrome associated with pernicious anaemia.

AIM: To determine whether there is an association between pernicious anaemia and antiphospholipid antibody syndrome. METHODS: Fifteen patients with pernicious anaemia and 11 patients with iron deficiency anaemia (controls) were evaluated for clinical parameters of thrombosis and/or the presence of antiphospholipid antibodies, antinuclear antibodies or lupus anticoagulant. RESULTS: One asymptomatic patient with pernicious anaemia had laboratory features suggestive of the antiphospholipid syndrome. An additional three patients in each group had slightly elevated antiphospholipid antibody concentrations, within one standard deviation of the normal range. CONCLUSION: The association between pernicious anaemia and antiphospholipid antibody syndrome is rare and evaluation should be guided by clinical indications.

Adult↗

Coordination of fast and slow rhythmic neuronal circuits.

Interactions among rhythmically active neuronal circuits that oscillate at different frequencies are important for generating complex behaviors, yet little is known about the underlying cellular mechanisms. We addressed this issue in the crab stomatogastric ganglion (STG), which contains two distinct but interacting circuits. These circuits generate the gastric mill rhythm (cycle period, approximately 10 sec) and the pyloric rhythm (cycle period, approximately 1 sec). When the identified modulatory projection neuron named modulatory commissural neuron 1 (MCN1) is activated, the gastric mill motor pattern is generated by interactions among MCN1 and two STG neurons [the lateral gastric (LG) neuron and interneuron 1]. We show that, during MCN1 stimulation, an identified synapse from the pyloric circuit onto the gastric mill circuit is pivotal for determining the gastric mill cycle period and the gastric-pyloric rhythm coordination. To examine the role of this intercircuit synapse, we replaced it with a computational equivalent via the dynamic-clamp technique. This enabled us to manipulate better the timing and strength of this synapse. We found this synapse to be necessary for production of the normal gastric mill cycle period. The synapse acts, during each LG neuron interburst, to boost rhythmically the influence of the modulatory input from MCN1 to LG and thereby to hasten LG neuron burst onset. The two rhythms become coordinated because LG burst onset occurs with a constant latency after the onset of the triggering pyloric input. These results indicate that intercircuit synapses can enable an oscillatory circuit to control the speed of a slower oscillatory circuit, as well as provide a mechanism for intercircuit coordination.

Animals↗

Synaptic depression creates a switch that controls the frequency of an oscillatory circuit.

Synaptic depression is a form of short-term plasticity exhibited by many synapses. Nonetheless, the functional significance of synaptic depression in oscillatory networks is not well understood. We show that, in a recurrent inhibitory network that includes an intrinsic oscillator, synaptic depression can give rise to two distinct modes of network operation. When the maximal conductance of the depressing synapse is small, the oscillation period is determined by the oscillator component. Increasing the maximal conductance beyond a threshold value activates a positive-feedback mechanism that greatly enhances the synaptic strength. In this mode, the oscillation period is determined by the strength and dynamics of the depressing synapse. Because of the regenerative nature of the feedback mechanism, the circuit can be switched from one mode of operation to another by a very small change in the maximal conductance of the depressing synapse. Our model was inspired by experimental work on the pyloric network of the lobster. The pyloric network produces a simple motor rhythm generated by a pacemaker neuron that receives feedback inhibition from a depressing synapse. In some preparations, elimination of the synapse had no effect on the period of the rhythm, whereas in other preparations, there was a significant decrease in the period. We propose that the pyloric network can operate in either of the two modes suggested by the model, depending on the maximal conductance of the depressing synapse.

Action Potentials↗

Deletion of 6q27 in chronic lymphocytic leukemia and multiple myeloma detected by fluorescence in situ hybridization.

Nonrandom deletions of the long arm of chromosome 6 (6q) are associated with various lymphoid malignancies. It has been suggested that deletions of 6q25-27, 6q21, and 6q23 typically occur in intermediate-grade, high-grade, and low-grade lymphomas, respectively. We used fluorescence in situ hybridization (FISH) to evaluate the occurrence of 6q27 deletion in chronic lymphatic leukemia (CLL) and multiple myeloma (MM). 6q27 deletion was detected in 21% of patients with CLL and in 28% of patients with MM. The percentage of cells containing deletions ranged between 25-49. Two patients with MM had progressive disease and the aberration was detected in both. We conclude that FISH is a sensitive method to detect 6q27 deletion in lymphoproliferative disorders. Also, this deletion is not specific to intermediate-grade lymphomas, but occurs also in CLL and MM.

Aged↗

Network oscillations generated by balancing graded asymmetric reciprocal inhibition in passive neurons.

We describe a novel mechanism by which network oscillations can arise from reciprocal inhibitory connections between two entirely passive neurons. The model was inspired by the activation of the gastric mill rhythm in the crab stomatogastric ganglion by the modulatory commissural ganglion neuron 1 (MCN1), but it is studied here in general terms. One model neuron has a linear current-voltage (I-V) curve with a low (L) resting potential, and the second model neuron has a linear current-voltage curve with a high (H) resting potential. The inhibitory connections between them are graded. There is an extrinsic modulatory excitatory input to the L neuron, and the L neuron presynaptically inhibits the modulatory neuron. Activation of the extrinsic modulatory neuron elicits stable network oscillations in which the L and H neurons are active in alternation. The oscillations arise because the graded reciprocal synapses create the equivalent of a negative-slope conductance region in the I-V curves for the cells. Geometrical methods are used to analyze the properties of and the mechanism underlying these network oscillations.

Animals↗

Replication pattern in cancer: asynchronous replication in multiple myeloma and in monoclonal gammopathy.

In this study we evaluated the replication pattern and cell-cycle dynamics of cells from patients considered to have a premalignant condition (monoclonal gammopathy, or MGUS) and patients with multiple myeloma (MM), as well as healthy controls. We applied the fluorescence in situ hybridization (FISH) technique with the TP53, RB-1 and 21q22 loci on the patient's cells. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronic replication was significantly higher in the cells from MM patients, with intermediate value in the cells from MGUS, while the lowest rate was in cells from controls. We suggest that these results may reflect the changes in gene replication and cell-cycle progression that occur in premalignant and malignant cells.

Aged↗