Biomedical subjects
Publications and source records attributed to A Shahar.
Acute liver failure occurred in a 59-year-old man with congestive heart failure within 4 days of oral loading with amiodarone. Hepatic toxicity of amiodarone leads to 2 histologic pictures: pseudo-alcoholic hepatitis and phospholipoidosis. Immune mechanisms are possible in amiodarone hepatotoxicity.
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We describe here a culture system for long-term growth of organotypic slices of spinal cord, with attached dorsal root ganglia (DRG) derived from 13-14 day mouse fetuses. This is a unique in vitro tool in which both central and peripheral nervous tissue grow and differentiate in culture to become heavily myelinated. During cultivation the slices and the ganglia become flattened so as to allow microscopical and immunocytochemical staining. When both central and peripheral myelin had been formed (usually around the third week of cultivation), cultures were infected with 5 x 10(6) PFU of West Nile Virus (WNV). Progeny virions appeared first in about 10% of the neurons and were subsequently observed between lamellae in the central myelin sheath of several axons. Such viral arrangement in relation to myelin membranes, might provide a novel concept for a possible mechanism underlying slow viral infection.
In two patients with carotid artery stenosis and anemia, neurological deficits appeared whenever the hemoglobin level fell below a critical level of 5-6 g/dl and resolved with correction of the anemia. Profound anemia should be considered as a cause of focal neurological deficit, especially if there is evidence of cerebral atherosclerosis.
The microscopic features of a spontaneous uterine granular cell tumour in a Fischer 344 rat are described. The location of the tumour is novel for the rat. The neoplasm is characterized by the presence of cells with cytoplasmic granules which were PAS positive and diastase resistant. Electron microscopy and immunohistochemistry results are presented and the origin of the tumour is discussed.
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The pathogenicity of two encephalitic Togaviruses, Sindbis virus (SV), an alphavirus, and West Nile virus (WNV), a flavivirus, was studied in organotypic cultures of fetal mouse spinal cord slices grown in roller tubes. After about 3 weeks in vitro, during which time the cultures became abundantly myelinated, they were infected either by 5 X 10(5) PFU SV or by 5 X 10(6) PFU WNV per culture. The viruses caused different patterns of cytopathogenicity: SV induced severe cytotoxicity in all glia cells and neurons with concomitant demyelination within 48 hr. In contrast, WNV, even 4 days after infection, caused only mild cytopathic effects mainly to neurons and astrocytes and a slight degree of damage to the myelin sheath. A most remarkable finding was the entrapment of WNV particles in the interperiod lines of the myelin sheaths. Treatment of cultures with mouse alpha and beta interferon prior to their infection with either virus protected the cultures from any viral damage. Long-term exposure of non-infected control organotypic cultures of fetal spinal cord slices to mouse interferons had no significant effect on neuronal and glial differentiation, and myelin formation.
The effect of prenatal irradiation was studied in organotypic cultures of hippocampus, prepared from newborn rats that had been exposed to whole-body irradiation of 1 Gy from a 60Co-source at day 13 of pregnancy. Light and electron microscopic observations showed remarkable damage to neuronal mitochondria accompanied by extensive swelling, vacuolation of the Golgi complex, and formation of multilamellar bodies and vesicles of the lysosomal type. In contrast to neuronal alterations, no delay in synaptogenesis or onset of myelination was observed based upon the absence of significant morphological changes in synapses and myelin sheaths. Using this tissue culture model it could be confirmed that prenatal exposure to irradiation, even at low doses, induces specific morphological changes in the brain.
Organotypic spinal cord cultures infected with West Nile Virus (WNV) exhibited a remarkable arrangement of virions among lamellae of the myelin sheath. Virions were first observed in neurons and only at day 4 after infection appeared within the myelin lamellae. Virions were observed only in the central myelin, aligned along the interperiod lines and therefore attached to the outer side of the oligodendrocyte membrane. In spite of this peculiar location of the virions, their presence was not associated with severe damage to the axon or to the myelin sheath. The causes of the formation of this viral pattern, its morphological features, and the role which it might have in viral infection in vivo are considered.
In stationary cultures of dissociated brain and spinal cord grown on microcarriers (MCs), the neuronal and ependymal cells attached to the MCs forming floating aggregates in which they grow in a three-dimensional pattern. The glial and meningeal elements on the contrary, tend to dissociate from the aggregates and adhere to the plastic dish where they divide to form a monolayer. This different behavior of CNS components is not observed in rotating cultures in which all CNS cells remain attached to the MCs and develop into mature floating structures. This cell separation in stationary MC-cultures which is documented here by SEM and immunocytochemistry, may be useful for analysis and evaluation of the metabolic biochemical events of each of the cellular components derived from the same culture.
Rats were exposed for 2 h either to 115 dB SPL noise, to 5% oxygen in nitrogen (hypoxia) or to both hypoxia and noise. Auditory nerve-brainstem evoked responses (ABR) to 80 dB HL clicks and threshold were recorded prior to exposure, immediately (5-10 min) after the exposure, 2 h after and 2 weeks after the exposure. The findings in each experimental animal were compared to those in the control (non-exposed) group and to those in the other groups. Thresholds were elevated in each of the experimental groups, but these were temporary threshold shifts, since 2 weeks following the exposure, threshold had returned to normal. Latencies (wave I and the IV-I interpeak latency difference- (IPLD] were prolonged in the groups exposed to hypoxia (hypoxia alone and hypoxia + noise). These results are discussed in view of possible mechanisms of these noise and hypoxia induced temporary threshold shifts.
Symptoms of vocal attrition were surveyed with a questionnaire in 130 Israeli women army instructors, a high-risk group for vocal attrition, and in 386 Israeli women recruits, presumably a low-risk group. Results showed 1. a high prevalence of symptoms in both groups, but a significantly higher prevalence among the instructors; 2. significant correlation between number of symptoms and rapid, excessive, and loud speech habits in both groups; and 3. significant correlation between number of symptoms and difficulties in performing instructional duties. These findings suggest that 1. vocal attrition is related to both external demands on the voice and idiosyncratic speech habits; and 2. vocal attrition has a significant impact on performance and work-efficiency.
Extended high-frequency (HF) audiometry and auditory-nerve brain-stem-evoked responses (ABR) were carried out on two groups of subjects with normal hearing sensitivity. The experimental group comprised 17 subjects with tinnitus, while the control group consisted of age- and sex-matched subjects, not suffering from tinnitus. The aim of the study was to determine whether extended HF audiometry or ABR might reveal significant differences between these two groups of subjects with normal hearing sensitivity. In addition, the characteristics of tinnitus in subjects with normal audiograms were discussed. The results of extended HF audiometry showed no significant differences between the subjects with and without tinnitus. The ABR parameters considered were also within normal limits bilaterally. Based on the methods employed in this study, tinnitus in normal listeners does not appear to reflect appreciable damage in the cochlea or in the brain-stem auditory pathways. The authors present some suggestions for future research.
The efficacy of self-hypnosis (SH) on tinnitus relief was compared with two control procedures: 1) presentation of a brief auditory stimulus (BAS) to the ear with tinnitus; 2) waiting list (WL), i.e. patients receiving no formal treatment. The results have shown that 73% of SH subjects reported disappearance of tinnitus during treatment sessions, as compared with only 24% in the BAS group. Moreover, the short-term (1 week) and long-term (2 months) symptom profiles of only SH subjects revealed a significant improvement. Thus, SH may well be a beneficial method for the relief of tinnitus.
Exposure to noise is unfortunately inevitable in military training. The incidence of hearing loss due to basic training was examined in a sample of 1000 recruits before enlistment and after 4 months of basic training. Audiometric tests and personal questionnaires revealed that after basic training 33.7% had developed hearing loss in the high frequency range (6-8 KHz), 3% had noise-induced hearing loss (2-5 KHz), while 60% still had normal hearing and 3.5% had hearing impairment due to various other causes. The left ear was more often affected and there was a tendency towards greater damage to hearing in lightly pigmented subjects. An initial hearing loss at 6-8 KHz may be related to individual susceptibility to noise-induced hearing loss.
A diversity of pathogenic effects was observed in two complementary culture systems following their exposure to the anesthetic agents. Thiopental sodium and ketamine hydrochloride. The cytotoxic effects of both agents in these two culture types were reversible and dose-related. In organotypic spinal cord slice cultures, thiopental sodium caused general toxicity but no demyelination, while ketamine hydrochloride induced, to a varied extent, damage of the myelin sheath and degeneration of mitochondria into multilamellar bodies. In autologous nerve-muscle co-cultures both anaesthetic agents caused the arrest of muscle contractions. However, when added to skeletal muscle cultures, the drugs differed in their effect. Thiopental sodium did not inhibit spontaneous muscle contractions indicating, as in the case of Tubocurarine, a direct effect of the drug on the neuromuscular junction. Ketamine hydrochloride, in contrast, arrested spontaneous muscle contractions, implying that it did not directly affect the neuromuscular synapse.
Reports on a potential relationship between noise-induced hearing loss (NIHL) and cardiovascular as well as biochemical measures are controversial. This study compares the means of certain cardiovascular and biochemical measures in subjects with NIHL with those in subjects exposed to similar occupational noise, but demonstrating normal hearing. This might indicate certain predisposing factors for NIHL. Eight hundred noise-exposed subjects were divided into two age-matched hearing groups (NIHL and normal hearing). The results showed that the mean values of all the variables examined in both hearing groups were within the normal range. No significant differences were found between the two groups in terms of the distribution of subjects for the indices measured.