Antibodies to different isoforms of the heavy neurofilament protein (NF-H) in normal aging and Alzheimer's disease.

Sera of normal controls and of patients with neurological diseases contain antineurofilament antibodies. Recent studies suggest that biochemically and immunologically distinct subclasses of neurofilaments occur in different types of neurons. Alzheimer's disease (AD), the major cause of dementia, is associated with a marked degeneration of brain cholinergic neurons. In the present work we characterized the repertoire and age dependence of antineurofilament antibodies in normal sera and examined whether the degeneration of cholinergic neurons in AD is associated with serum antibodies directed specifically against the neurofilaments of mammalian cholinergic neurons. This was performed by immunoblot assays utilizing neurofilaments from the purely cholinergic bovine ventral root neurons and from the chemically heterogeneous bovine dorsal root neurons. Antibodies to the heavy neurofilament protein NF-H were detected in normal control sera. Their levels were significantly higher in older (aged 70-79) than in younger (aged 40-59) subjects. These antibodies bound similarly to bovine ventral root and dorsal root NF-H and their NF-H specificity was unchanged during aging. In contrast, the levels of IgG in AD sera that are directed against ventral root cholinergic NF-H were higher than those directed against the chemically heterogeneous dorsal root NF-H. Immunoblot experiments utilizing dephosphorylated ventral root and dorsal root NF-H and chymotryptic fragments of these molecules revealed that AD sera contain a repertoire of antimamalian NF-H IgG. A subpopulation of these antibodies binds to phosphorylated epitopes that are specifically enriched in ventral root cholinergic NF-H and that are located on the carboxy terminal domain of this molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of experimental allergic encephalomyelitis by anterior hypothalamic lesion in rats.

Bilateral electrical lesions were performed in the anterior hypothalamus (AH) and hippocampus (HC) of female Lewis rats. AH but not HC lesions were found to inhibit the appearance of clinical signs typical of experimental allergic encephalomyelitis (EAE). The incidence of EAE was 17.2% and the duration was 1.33 +/- 0.07 days after AH lesions compared with an incidence of 85% and duration of 4.81 +/- 0.6 days in the controls. Destruction of the AH was followed by decreased levels of antibodies to myelin basic protein and increased reactivity of splenic lymphocytes to concanavalin A, but did not affect the extent of mononuclear cell infiltration within the brain and spinal cord.

Disruption of automatic speech following a right basal ganglia lesion.

Following a right basal ganglia lesion, a right-handed man, age 75, was unable to recite familiar verses. Serial automatic speech, singing, recitation of rhymes, and swearing were impaired, and only idioms and social greetings were preserved. Speech no longer contained overused phrases and he could comprehend automatic speech. In contrast, propositional speech was preserved in both French and Hebrew. Right basal ganglia lesions may impair production but not comprehension of automatic speech.

Antibodies from Down's syndrome patients bind to the same cholinergic neurofilament protein recognized by Alzheimer's disease antibodies.

Down's syndrome (DS) patients who survive beyond the third decade develop brain lesions characteristic of Alzheimer's disease (AD). Sera of AD patients contain antibodies that bind specifically to the heavy neurofilament protein (NF-H) of Torpedo cholinergic neurons. In the present report, we examined whether the AD-like pathologic changes in DS are associated with the existence of such antibodies. Our findings show that IgG of older DS patients (greater than 30 years) binds to Torpedo cholinergic NF-H more readily than does that of young DS patients (less than 30 years) and age-matched normal controls. In contrast, the extent of binding of IgG from the young and older DS groups to Torpedo and bovine spinal cords NF-H is similar and equal to that of normal controls. These findings suggest that older DS patients, like AD patients, contain anti-NF-H IgG that binds specifically to epitopes highly enriched in Torpedo cholinergic NF-H.

Contributions of the parietal and frontal lobes to sustained attention and habituation.

The parietal cortex may be important in sustaining attention toward visual stimuli in peripheral space whereas the frontal cortex may mediate selective attention through habituation to peripheral stimuli. To test this hypothesis, patients with focal lesions of either the parietal or frontal cortex or both and normal controls were studied using a paradigm known as Troxler fading. Accordingly, if one fixates on a centrally located stimulus and attends to a stationary stimulus in peripheral vision, the peripheral stimulus quickly fades from awareness (i.e. Troxler fading: Troxler [Verschwinden, unseres, Opthal, Vol. 2, pp. 51-53. Fromann, Jena, 1804]). Movement of the peripheral stimulus on the retina normally prevents Troxler fading. Results indicated that patients with parietal lesions not only reported accelerated Troxler fading but also reported fading of moving peripheral stimuli contralateral to their brain lesion. In contrast, patients with frontal lesions rarely reported Troxler fading. In one patient with a left parietal and a right frontal lobe lesion fading was hemi-spatially dissociated, being accelerated in right hemispace but absent in left hemispace. These observations suggest that the parietal and frontal cortices play complementary roles in attentional processing.

Effect of hypothalamic lesions on experimental autoimmune diseases in rats.

The development of experimental autoimmune encephalomyelitis (EAE) was prevented in rats immunized with encephalitogenic antigen two weeks, but not twelve weeks, after stereotaxic electrolytic destruction of the anterior hypothalamus. Serum antibody level to the antigen myelin basic protein was decreased, and in vitro lymphocyte transformation response to a mitogen was increased. On the other hand, incidence and intensity of chronic experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor immunization were higher in rats with anterior hypothalamic lesion. In addition, expression of EAE in rats was inhibited when dopamine and norepinephrine in brain were depleted due to intraventricular injection of 6-hydroxydopamine or subcutaneous injection of reserpine. The study indicates hypothalamic modulatory effects on autoimmune response as well as possible involvement of neurotransmitters in this kind of neuroimmunomodulation.

An association between multiple sclerosis and type I diabetes mellitus.

We report five patients who had multiple sclerosis (MS) associated with type I diabetes mellitus (TODM). Examination of the Israeli National Neurological Disease Register revealed the prevalence of TODM among 334 MS patients under the age of 30 years to be 8.98 per 1,000. This is significantly higher than the prevalence of TODM in the general population of Israel for the same age group, which is 0.095 per 1,000. MS and TODM share clinical, epidemiological and immunological features, and both diseases have a target site that is neuroectodermal in origin. The association between these two putative autoimmune diseases may suggest a similar pathogenetic mechanism.

Antibodies to ganglioside GM1 in patients with Alzheimer's disease.

Gangliosides are thought to have a role in neuronal development and regeneration while anti-ganglioside antibodies have been shown to impair these processes. In the present work we examined whether the neuronal degeneration in Alzheimer's disease is associated with the presence of anti-ganglioside antibodies. A significant level of antibodies specific to ganglioside GM1 but not to other gangliosides (GD1a, GD1b, GT1b and GQ1b) was found in patients with Alzheimer's disease as compared to normal age matched controls. A high level of antibodies to GM1 was also found in patients with multi-infarct dementia and Parkinson's disease with dementia but not in non-demented patients with other neurodegenerative diseases. These results may reflect a specific change in ganglioside metabolism which is associated with the neurodegenerative processes underlying Alzheimer's disease and other causes of dementia.

The neglected page.

Normal subjects bisect vertical lines above the true midpoint. We posited that the portion of the page farthest from the line or the page's geometric center, though not the focus of attention, would still engage attention. Therefore, subjects should make bisection errors in the direction of the distant portion or geometric center. We expected the greatest superior bisection errors to be made when lines were placed at the bottom of the page and the smallest errors to be made when the lines were placed at the top of the page. Ten young, normal subjects bisected vertical lines placed in 1 of 3 positions on a page (top, center, bottom) with the page located in 1 of 3 spatial locations (superior, middle, inferior). The results of our study were consistent with our predictions. Thus, although the page on which a line is bisected is often ignored, it is not neglected.

Cortical second messengers after NBM damage: no change in responses to cholinergic agonists.

Damage to the nucleus basalis of Meynert (NBM) decreases acetylcholine (ACh) innervation of cortex. We explored transmission of cholinergic messages in cortex 2-3 weeks after such damage. The NBM damage was unilateral and the ipsilateral denervated cortex was compared to the contralateral nondenervated cortex. The response to carbachol, a muscarinic ACh receptor-agonist, was measured by inhibition of forskolin-induced cAMP accumulation in cortical membranes and by formation of inositol phosphate (IP) in cortical slices. No difference was found in the carbachol effects between ipsi- and contralateral cortices. Thus, we find no evidence of either receptor loss or receptor supersensitivity. There was, however, a significant decrease in K(+)-stimulated IP formation in the cortex ipsilateral to the damage which probably reflected loss of cholinergic terminals. When comparing the cortex contralateral to NBM damage with the cortex contralateral to sham damage in control rats, no difference was found in any of the above parameters. When severe cognitive deficits are observed, 2-3 weeks after NBM damage, loss of presynaptic ACh is the main change in cortical cholinergic transmission.

Passive listening and task related P300 measurement for the evaluation of dementia and pseudodementia.

The late evoked potential P300 was tested in three groups of subjects. These consisted of 25 patients suffering from dementia (Group I), 14 patients suffering from pseudodementia due to severe depressive disease (Group II), and 24 age-matched normal controls (Group III). Since patients suffering from dementia frequently have difficulties in counting targets in the "oddball" paradigm, we evaluated the usefulness of a Passive Listening condition. With the classical "oddball" paradigm, 78% of the subjects were correctly related to one of the three groups examined. The "P300-like" wave form produced in the Passive Listening condition was not found to be sensitive enough to allow such a distinction.

Limited fluctuations in T lymphocyte parameters in the human as a marker of aging.

Analysis of T lymphocytes was performed on SENIEUR protocol selected young and old individuals. Parameters examined were phenotype and reactivity to phytohemagglutinin (PHA) measured under standard and limiting dilution conditions. Blood samples were drawn twice, at an interval of one month, to establish the stability of values measured. The results showed no statistically significant difference as in proportion of CD4(+) and CD8(+) cells between the young and old peripheral blood samples. Standard proliferative responses to PHA were reduced in the old. Limiting dilution analyses revealed a reproducible, pronounced decrease in the frequency of precursors of PHA-reactive T lymphocytes in the old. Twice repeated determinations showed fluctuations in the above parameters in the young, whereas in the old the values were lower and less fluctuating. This observation was not associated with any change in the clinical status of the elderly subjects during the one-year follow up period.

Folk, traditional and conventional medicine among elderly Yemenite immigrants in Israel.

BACKGROUND: Migration leads to changes in almost all areas of life including health. But how far are health beliefs also preserved, and how far are they affected by the process of acculturation to the host society? OBJECTIVES: To examine the difference between behavior and attitudes towards conventional and traditional medicine among elderly Yemenite immigrants. METHODS: A community-based study was conducted in the Yemenite neighborhoods in the city of Rehovot. All inhabitants of Yemenite origin over the age of 70 were identified from the population register, excluding those who were institutionalized or demented. Social work students interviewed them at home. The questionnaire inquired after health problems in the preceding month. For each of these problems, the respondent was asked whether any mode of treatment had been employed--Yemenite folk remedies, conventional medical care, or other. Their attitudes towards Yemenite folk medicine and conventional medicine were recorded. Socioeconomic data included their current age, age at immigration, year of immigration, marital status, gender, religiosity, and education. RESULTS: A total of 326 elderly people were identified who fulfilled the selection criteria, of whom 304 (93%) agreed to be interviewed. Of these, 276 (91%) reported at least one health problem in the preceding month, providing 515 problems of which 349 (68%) were reported to a conventional medical doctor while 144 (28%) were treated by popular folk remedies. Fifty-nine problems (11.5%) were treated by specifically Yemenite traditional remedies, mostly by the respondents themselves (38/59) rather than by a traditional healer. Immigrants who arrived in Israel over the age of 30 years, as compared to respondents who immigrated at an earlier age and grew up in Israel, were more likely to use traditional Yemenite remedies (24.4% vs. 8.2%, P < 0.005). CONCLUSION: Aged Yemenite Jews in Israel prefer modern medicine. The earlier the immigrant arrived in Israel, the more positive the attitude towards modern medicine and the less use made of traditional Yemenite healing.

Physical and psychosocial benefits of modified judo practice for blind, mentally retarded children: a pilot study.

A modified form of judo training was practiced by a class of 7 blind, mentally retarded children with associated neuropsychiatric disturbances. The biweekly training program lasted for 6 months. Analysis indicated improvements in physical fitness, motor skills, and psychosocial attitude. The authors concluded that a modified form of judo can be used as a therapeutic, educational, and recreational tool for multiply handicapped children.

Chronic inflammatory demyelinating polyradiculoneuropathy: features and prognostic factors with corticosteroid therapy.

Of a series of 16 cases with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 14 patients were treated with high-dose steroid therapy (HDST, 1.0-1.5 mg/kg/day of prednisone). The average functional disability score (FDS) before treatment was 3.06 +/- 0.11 (maximum FDS = 4). There was a significant improvement under this treatment (FDS = 1.43 +/- 1.12, p less than 0.001). Maximal improvement appeared in 10 patients after 4 weeks of HDST. Following improvement, repeated attempts were made to taper off HDST in 9 patients, 8 of them developed 26 relapses. In most of the patients medium-dose steroid therapy (MDST) with 0.5-0.75 mg/kg/day of prednisone was continued, sometimes with addition of other immunosuppressive medication. The duration of HDST + MDST was between 0.5 and 6.0 years (average 2.6). The following factors were found to correlate with better response to HDST: shorter duration of CIDP, milder neurological deficit, milder decrease of nerve conduction velocity, younger age and being female. Global distribution of weakness, muscle atrophy and a positive Babinski sign were predictive of poor prognosis. Involvement of cranial nerves and level of protein in the cerebrospinal fluid did not correlate with the results of HDST. The risk of relapse was higher with shorter periods of HDST and with more rapid tapering off of HDST. The results indicate that treatment with HDST should be initiated as early as possible, a period of stability of remission is needed before tapering off, and lowering of HDST must be very gradual.

Neglect of near peripersonal space. Evidence for multidirectional attentional systems in humans.

Neglect is most commonly observed and studied in the horizontal spatial dimension. Vertical neglect has been described in a few studies. We now report on a patient with near radial space neglect following bilateral posterior parietal lobe lesions. Our patient also had neglect of inferior vertical and left horizontal space. These spatial deficits appear primarily attentional. Our findings compliment other studies that demonstrate neglect may occur in multiple spatial dimensions and provide evidence for a three-dimensional attentional system in humans. Whereas neglect of inferior vertical space may be associated with bilateral parietal lobe lesions, neglect of superior vertical and far radial space has been associated with bilateral inferior temporo-occipital lesions.

Iron accumulation in the rat basal ganglia after excitatory amino acid injections--dissociation from neuronal loss.

The current study examines in an animal model the relation of excessive iron accumulation in the basal ganglia to the pathology of Parkinsonism and Hallervoden-Spatz disease. Following a unilateral microinjection of excitatory amino acids, kainate, or quinolinate to the anterior olfactory nucleus/ventral striatal region, an increase in histochemical iron concentration was observed in the ipsilateral ventral pallidum, the islands of calleja, the globus pallidus, the entopeduncular nucleus, the ventral thalamus, and the substantia nigra pars reticulata. The iron was observed both in glia and as intensification of patches in the neuropil. In a second group of rats, after microinjection of ibotenate or quisqualate to the nucleus basalis of Meynert, iron accumulated in the ipsilateral entopeduncular nucleus and pars reticulata of substantia nigra. Increased iron accumulation, compared to that in the contralateral side, was stable for months after a single microinjection. In the basal ganglia distal from the site of EAA injection, no gross morphological changes were associated with the increased iron accumulation. The implications of these findings to the pathology of Parkinson's and Hallervorden-Spatz diseases are discussed.