Neutralizing antibodies to canine distemper and measles virus in multiple sclerosis.

Serum neutralizing antibody to canine distemper virus (CDV) was measured in 142 patients with multiple sclerosis (MS), an equal number of age and sex-matched normal controls, and 75 patients with other neurological disorders. An elevated antibody titer was found in the MS population compared to controls. Measles-neutralizing antibody was also found to be elevated in 128 patients with MS. The mean ratio of measles to CDV antibody was similar in the control and MS groups, but a wide range of measles to CDV ratios was found in individual patients and controls. No significant correlation was found between IgG levels and neutralizing antibody titers in MS sera. While the increased titer of measles and CDV antibody may represent a non-specific immunological response, these findings are also consistent with the hypothesis that CDV or a closely related measles virus may stimulate the increased level of measles and CDV antibodies found in MS sera.     

The use of neurotoxins to characterize the rates and subcellular distributions of axonally transported dopamine-beta-hydroxylase, tyrosine hydroxylase and norepinephrine in the rat brain.

The effect of 6-hydroxydopamine (6-OHDA), colchicine and cytochalasin B on the transport and subcellular distribution of proteins, tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) were studied in the noradrenergic neurons of the rat locus coeruleus (LC). Four waves of transported 3H-labeled proteins and glycoproteins, defined by previous studies, as well as hypothalamic levels of TH, DBH and NE, were examined after injection of each neurotoxin into the ascending dorsal noradrenergic bundle. Blockade of subcellular components of TH, DBH and NE was compared to their endogenous hypothalamic distributions. 6-Hydroxydopamine variably blocked transport of all 4 waves of 3H protein and bilateral injections decreased hypothalamic levels of TH, DBH and NE by 58.2, 56.9 and 52.2% of controls, respectively. Cytochalasin B blocked transport of protein waves I (72--192 mn/day) and III (13--20 mm/day) and decreased hypothalamic levels of TH to 60.1% of control after bilateral injections. Colchicine blocked transport of waves I, II (24--48 mm/day) and V (1.4--2.9 mm/day) and blocked [3H]NE transport, while decreasing hypothalamic levels of DBH and NE to 56.6 and 69.3% of control after bilateral injections. Colchicine and 6-OHDA, but not cytochalasin B, caused a backup of DBH immunofluorescence proximal to the injection site. DBH and NE appeared to be transported primarily in particulate form, while TH transport was predominantly soluble in distribution. None of the toxins differentially affected the transport of one particular subcellular component of TH, DBH or NE. Based on the differential blocking effects of these toxins, DBH and NE appeared to be associated with wave II, and TH with wave III, travelling at 24--48 mm/day and 13--20 mm/day respectively.     

Lymphoid cell infection by measles virus in newborn hamsters : Role for monocytes in virus spread to distant sites

Following intraperitoneal inoculation of measles (HBS) virus into newborn hamsters widespread but variable productive lymphoid tissue infection was detected by a sensitive viral isolation technique. Peritoneal wash cells and spleen were the most common sites of infection. Virus was frequently isolated from the bone marrow and was commonly found in multiple lymph nodes. Thymic infection was only rarely demonstrated. A mononuclear cell associated viremia was demonstrated by Ficoll-hypaque fractionation of peripheral blood from animals receiving both high- and low-dose virus. Infection was present in both plastic adherent and non-adherent fractions of the blood mononuclear cells. The infected cell population in the spleen had both nylon wool and plastic adherent characteristics and infection was therefore thought to be macrophage-associated. The possible relevance of such macrophage associated infection is discussed with regard to the pathogenesis of natural measles infection and the immunosuppression observed in measles-infected hosts.     

The regulation of regional blood flow in the brain by visual input

The blood supply to several regions of the chick brain is rapidly decreased following reduction of visual input by monocular eyelid Suture. This decrease is not confined to the primary visual area (the optic lobe) contralateral to and innervated by the sutured eye but is also apparent in the indirectly innervated cerebral hemispheres contralateral to the treated eye.After periods of bilateral eyelid suture, exposure of a single eye to patterned light by suture removal results in a rapid increase of blood flow through contralateral cerebral regions directly or secondarily innervated by the exposed eye. This response appears to be more closely related to the intensity rather than to the information content of incident light.The ability to regulate regional cerebral blood flow is lost following reduction of brain catecholamine levels with reserpine. However, cerebral blood flow is still responsive to afferent sensory input, in the presence of a concentration of carbon dioxide sufficient to cause near maximal dilation of cerebral blood vessels. This suggests that variations of vascular supply to specific brain regions may in part be effected by direct autonomic nervous mechanisms regulating the diameter of blood vessels within the brain.     

Species cross-reactivities of antisera reacting with myelin basic peptide 43–88 : Applications for the detection of peptide in rabbit plasma

Previous investigations have demonstrated that the detection and measurement of peptides of myelin basic protein (BP) by immunochemical procedures are heavily dependent on the conformation of BP peptides and the specificities of antisera to these peptides. In the present study a double antibody-radioimmunoassay was used to assess the species specificity of antisera from 4 rabbits and 2 sheep against myelin basic protein (BP) peptide 43-88. Although some antisera showed broad reactivity, others were selective for species of BP used in the immunogen. By optimizing the reaction of one of the sheep anti-human peptide 43-88 for detection of rabbit BP peptide 43-88, it was possible to detect immunoreactive BP peptide 43-88 in the plasma of rabbits previously injected with bovine BP peptide 43-88 and complete Freund's adjuvant (CFA). Peptide could be detected in plasma for 1-2 days immediately after subcutaneous injection and again between days 20 and 50. Plasma antibody to rabbit BP peptide 43-88 also appeared 15-20 days after immunization and persisted often in an oscillatory pattern reciprocal for the peptide level. Neither peptide nor antibody was detected in the plasma of normal rabbits or of rabbits injected with bovine spinal cord homogenate-CFA, bovine renal homogenate-CFA or CFA alone. There was no relationship of the level of immunoreactive BP peptide 43-88, antibody to this peptide or their patterns to clinical or neuropathological changes in the animals. Quantitation and analysis of BP peptides in body fluids of animals with diseases affecting central nervous system myelin may provide information relevant to human demyelinating diseases.     

Antibodies to viral and non-viral antigens in subacute sclerosing panencephalitis and multiple sclerosis demonstrated by thin-layer polyacrylamide gel isoelectric focusing,antigen immunofixation and autoradiography

Antibody activity in IgG zones separated by thin-layer polyacrylamide gel isoelectric focusing (PAGIEF) was determined in 3 patients with subacute sclerosing panencephalitis (SSPE), 4 patients with multiple sclerosis (MS) and 4 subjects with psychosomatic disorders, using antigen immunofixation and autoradiography. Viral (measles, herpes simplex type 1, mumps) and non-viral (purified bovine myelin, bovine myelin basic protein, bovine oligodendrocytes, MS and normal human brain extract) were used as antigens. All oligoclonal and some of the polyclonal CSF IgG zones in the patients with SSPE contained measles virus antibodies, as did some of the oligoclonal and polyclonal CSF IgG zones in 3 of the patients with MS. No antibodies were detectable in CSF or serum IgG zones against any of the non-viral antigens tested.     

Axonal transport of [H]fucosyl glycoproteins in noradrenergic neurons in the rat brain

The transport of [³H]fucosyl glycoproteins has been investigated in the noradrenergic pathway from the locus coeruleus (LC) to the hypothalamus in the rat brain by use of local injection ofl-[6-³H]fucose into the LC. Two discrete waves of³H-glycoprotein pass through the hypothalamus in a caudorostral direction traveling at 4 mm/h (96 mm/day) and 2 mm/h (48 mm/day) respectively. Both waves appear to originate from the LC at approximately 2 h after the injection of [³H]fucose, a time when incorporation into glycoprotein has not yet peaked in the LC. Lesioning the LC-hypothalamic pathway with 6-OHDA, but not carrier solution, blocks both waves of³H-glycoprotein demonstrating that transport occurs exclusively in the catecholamine axons within the pathway. DEAE-Sephadex chromatography combined with 6-OHDA lesions demonstrates clear differences in the character of³H-glycoproteins in the two waves undergoing transport. The relative lack of labelling of hypothalamic glycoproteins in the interval before and after these waves suggests that relatively few rapidly transported glycoproteins contribute to the non-terminal axon membrane and are probably primarily transported to the nerve terminal. No evidence for slow axoplasmic transport of [³H]fucosyl glycoproteins is found.     

Differential lateralization for positive and negative emotion in the human brain: EEG spectral analysis

The present experiment utilized EEG spectral analysis to investigate lateralization for emotional processes in the human brain. In frontal zones, a differential lateralization for positive and negative emotion was observed, with relative left-hemispheric activation (as measured by decreases in alpha abundance) for positive emotions and relative right-hemispheric activation for negative emotions. In parietal zones, a differential lateralization for verbal and spatial processes was observed, with relative left-hemispheric activation for verbal questions and relative right-hemispheric activation for spatial questions. Examination of EEG bands other than alpha (i.e. delta, theta, beta, and total power) suggested that emotional and cognitive processes are further distinguished by different EEG spectral patterns.     

Laterality and sex differences for visual recognition of emotional and non-emotional words

Clinical and experimental evidence indicate that the right hemisphere possesses a special capacity for emotional non-verbal material. The possibility that this ability would extend to language was tested with a lexical decision paradigm using tachistoscopic double simultaneous presentation of emotional and non-emotional words. Male subjects showed an overall right visual field superiority with the predicted effect of emotional words in the left visual field. In contrast, the field advantages for females were more variable and showed evidence of a larger effect of emotional words in the right visual field. The imageability potential of words also appeared to influence the female performance.     

Central nervous system vasculitis in cytomegalovirus infection

A 51-year-old man received cyclophosphamide, vincristine, procarbazine and prednisone in the treatment of a small-cell undifferentiated lymphoma. Two years later, he developed a rapidly progressive neurological syndrome characterized by a decline in alertness, deafness, blindness and paraplegia. Examination of his eyes revealed severe hemorrhagic chorioretinitis. Leg weakness was thought to be due to transverse myelopathy at a thoracic level. He had a grand mal convulsion and died from terminal bronchopneumonia.Autopsy examination of the eyes revealed sweeping destruction of the retina due to inclusion body chorioretinitis. The brain and spinal cord showed multiple small infarcts accounting for the deafness and paraplegia. The lesions were due to occlusive arteritis in gray and white matter. Veins were also involved.Tissue surrounding the foci of necrosis contained cells with intranuclear and intracytoplasmic inclusion bodies. Some of the Cowdry type A inclusion bodies were large, measuring 30 μm in diameter and were located in enlarged cells.Electron microscopy of retina and brain tissue disclosed virus particles compatible with cytomegalovirus.The subject of cerebral and ocular angiitis due to herpes virus infections is reviewed.     

In vitro cellular responsiveness in multiple sclerosis patients to a purified measles virus nuclear core and to other viral antigens

The Clausen modification of the peripheral blood buffy coat leukocyte migration test was used to test patients with multiple sclerosis, normal subjects and patients with other neurologic diseases for cell-mediated immunity to commercial measles virus, purified nuclear core material from a human neurotropic strain of measles virus, as well as to commercial preparations of rubella, mumps and parainfluenza HA₂. Leukocytes of multiple sclerosis patients showed significantly less mean inhibition of migration in the presence of both measles antigens, mumps and parainfluenza but no difference from controls when incubated with rubella. No correlation could be found between the degree of migration inhibition and concomitant serum anti-measles neutralization antibody titers to the same strain of virus. The use of purified viral antigens might result in more meaningful studies of the status of cell-mediated immunity to viral antigens in multiple sclerosis. The relationship of our findings to other studies in this area and to the pathogenesis of multiple sclerosis is discussed.     

Progesterone metabolism in the pineal, brain stem, thalamus and corpus callosum of the female rat

Specific brain regions, namely, thalamus, tectum, tegmentum, cerebellum, medulla and pineal, from five proestrous rats were incubated for 30 min with [3H]progesterone. After reverse isotopic dilution analysis, the following metabolites were identified in all incubations by purification to constant specific activity, derivative formation and/or gas liquid chromatography trapping: [3H]5alpha-pregnane-3, 20-dione (10-20% of the starting substrate except pineal -- 0.7%), [3H]3alpha-hydroxy-5alpha-pregnan-20-one (1.6-3.8% except for pineal -- 0.5%) and [3H]20alpha-hydroxy-4-pregnen-3-one (0.05-0.11%). Preliminary results from the corpus collosum incubation indicated the presence of the same metabolites. Although some apparent constant specific activities were obtained for 20alpha-hydroxy-5alpha-pregnan-3-one and 5beta-pregnane-3, 20-dione, the low levels of 3H associated with these steroids did not permit a definitive identification. The results indicate the presence of at least delta1-steroid 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase and 20alpha-hydroxysteroid dehydrogenase activities with progesterone as substrate in the brain regions examined.     

Attitudinal and behavioral correlates of coronary heart disease

The recognition of an association between coronary heart disease (CHD) and coronary prone behavior (CPB) has raised the question of whether behavior may directly affect coronary atherosclerosis. The relationship of coronary occlusion measured by arteriography and angina pectoris to questionnaire responses selected as consistent with the attitudes and behavior of CPB were examined retrospectively in 2215 employed male patients.

Nonbehavioral factors such as serum cholesterol and triglycerides were highly related to occlusion but not to angina. By comparison, most subjective attitudes and some quantitative behaviors consistent with CPB were overrepresented in angina but not in occlusion. Certain neurotic behaviors were also disproportionately represented in angina but not in occlusion.

These results indicate that attitudinal and behavioral aspects of CPB contribute to angina pectoris and perhaps indirectly to atherosclerosis. This association was greatest in patients older than 50 years, but comparable to some standard risk factors in younger patients also.     

A test of delayed recovery following stressful stimulation in four psychosomatic disorders

Sternbach proposed a three component model to account for the emergence of psychosomatic symptoms. He hypothesized that if an individual exhibited (1) marked response stereotypy, and (2) inadequate homeostatic restraints, then (3) exposure to activating situations would result in psychosomatic episodes. The main purpose of the present study was to examine the second component of the Sternbach model, homeostatic inadequacy, as indicated by impaired rate of recovery from stressful stimulation. In addition, the presence of response stereotypy was investigated in this study.

Ten subjects from each of 5 diagnostic groups (rheumatoid arthritis, essential hypertension, migraine headache, tension headache, and healthy controls) were observed under conditions of unstructured relaxation, easement (exposure to stimuli intended to enhance relaxation), mild stress, and recovery from stress. Forearm and forehead muscle potential, peripheral temperature, electrodermal response, heart rate and systolic and diastolic blood pressure were monitored during these sessions.

Although evidence of symptom specific response stereotypy was regularly observed, slowness of recovery did not emerge as a robust phenomenon in the four psychosomatic disorders investigated. The phenomenon was consistently observed in the arthritic subjects, absent in hypertensives and tension headache subjects, and ambiguous for migraine subjects.     

Morphology and distribution of cytoplasmic inclusions in adrenoleukodystrophy

We report some additional observations on the pathognomonic cytoplasmic inclusions in a typical case of adrenoleukodystrophy (ALD). Study of the linear inclusions by means of tilt-stage electron microscopy indicated that they represent trilaminar sheet-like structures distinct from materials seen in various other storage disorders. This study emphasizes that the inclusions in the adrenal and testicular parenchymal cells morphologically differ from those in the brain macrophages. In the latter they occur as membrane-bound discrete structures while in the parenchymal cells they are always seen lying free in the cytoplasm and associated with cleft-like spaces. This morphologic variation of the inclusions is noteworthy and probably reflects a biochemical difference in the storage materials in these two most severely affected organs. In addition, this study demonstrates the presence of linear inclusions within macrophages in otherwise normal-appearing liver, spleen, thymus and also in the renal tubular cells. These findings suggest that the abnormal materials containing very long chain fatty acids enter the blood stream and become sequestered in the reticuloendothelial system and possibly are also excreted in the urine. Detection of these abnormal fatty acids in blood and urine may simplify diagnosis of ALD.     

Multiple sclerosis. Electrofocused "bands" of oligoclonal CSF IgG do not carry antibody activity against measles, varicella-zoster or rotaviruses

Electrofocused serum and cerebrospinal fluid (CSF) specimens from patients with multiple sclerosis (MS) were analysed for immunoglobulins (Ig) and for antibodies to measles, varicella-zoster and rotaviruses by an imprint immunofixation method. Patterns of intrathecally synthesized antibodies to the 3 viruses differed from patterns of oligoclonal IgG in the CSF. A variable proportion of virus antibody bands (average 19% for measles antibodies, 8% for varicella-zoster antibodies, 31% for rotavirus antibodies) displayed isoelectric points identical to bands of IgG, but absorption with measles, varicella-zoster and rotavirus antigens produced no change in the bands of IgG and no quantifiable decrease of the CSF IgG. The results confirm previous evidence that the intrathecally synthesized viral antibodies so far demonstrated in MS are not carried by the oligoclonal bands of CSF IgG and account for only a minor fraction of the CSF IgG.     

The anterograde and retrograde retrieval ability of a patient with amnesia due to encephalitis

A patient with amnesia due to encephalitis was previously described in 1976 as having normal short-term memory and an intact ability to perform semantic analysis. Despite this ability, his retention beyond the limits of short-term memory was nearly nil. The present investigation sought to evaluate more completely the nature of this patient's retrieval deficit using a series of paradigms developed subsequent to his initial testing. Once again it was discovered that while his intact analytic abilities allowed retention of material in working memory, as soon as that working capacity was exceeded, retrieval of information became nearly impossible. It became apparent that the patient could not discriminate between a cue's most recently analyzed associate and the strongest existing associate to that cue in his semantic hierarchy. An analysis of his retrograde memory ability showed that he could retrieve almost no real episodes of either a public or private nature from his past. Instead, he seemed to rely on generalizations from his semantic memory to reconstruct “probable” events.     

A central processor for hierarchically-structured material: Evidence from broca's aphasia

Adults with localized cerebral insult were asked to construct non-linguistic, hierarchical tree structures which were analogues of syntactic trees thought to underlie sentences. It was found that only the Broca's aphasics had not remembered that the visuo-spatial material was organized heirarchically, although they had recalled the trees' symmetrical properties. Further, the Broca's aphasics tended to employ a chain-like constructional strategy in the creation of their trees. These findings suggest that the Broca's aphasics' constructions of non-linguistic, hierarchically-structured material may mirror their deficits in appreciating the hierarchical properties of sentential structures.     

Diagnostic accuracy of clinical data, quantitative electromyography and histochemistry in neuromuscular disease. A study of 105 cases

One hundred and five (105) cases of muscle weakness were reviewed in order to evaluate the reliability of clinical diagnosis, quantitative EMG, and muscle histochemistry in neuromuscular disorders. Patients were grouped into 3 categories: group I, disorders which could be diagnosed by clinical observation alone (38 patients); group II, disorders in which the EMG and biopsy were necessary for delineation (63 patients); disorders in which it was not possible to make a diagnosis because the clinical and laboratory studies were contradictory (4 patients). In group I, only one patient showed an inconsistency between clinical and laboratory data. In group II, the EMG and biopsy were concordant in all but 4 cases of Kugelberg-Welander syndrome with neuropathic EMG and myopathic biopsy. In group III, 4 patients had a myopathic EMG and neuropathic biopsy.The overall concordance of EMG and histochemistry was greater than 90%. The laboratory studies also discerned 2 different categories of disease, “neuropathic” and “myopathic”. The consistency in EMG and histochemistry correlation suggests that a true division between neuropathic and myopathic disorders exists.     

Interaction between phonological and semantic factors in auditory comprehension

This study compared Wernicke's and Broca's aphasic patients as to the influence of phonological vs semantic factors in their ability to make phonemic discriminations. Eight subjects of each diagnostic type participated in three experiments in which semantic processing played an increasing role. Experiment I was an auditory-auditory same-different match, Experiment II was an auditory-visual same-different match and Experiment III was an auditory vs visual multiple choice, introducing the possibility of either semantically or phonologically based errors. Wernicke's aphasics were more impaired than Broca's at all levels, but their performance was disproportionately impaired as semantic mediation was introduced. Semantically based errors outnumbered phonologically based errors in Experiment III, which showed that just as semantic processing demand increases the risk of phonological error, so does phonological difficulty increase the risk of semantic error.