Personality traits and psychophysiological reactions to a stressful interview in twins with varying degrees of coronary heart disease.

A series of male twin pairs aged 51–74 (mean 62), the majority of whom were discordant with regard to coronary heart disease (CHD), 17 monozygotic and 13 dizygotic pairs, were subjected to psychologic and psychophysiologic evaluation. None of a number of CHD-related psychologic measures differentiated significantly the “more healthy” from the “less healthy” partners. Two measures of Type A behavior as well as “muscular tension” and “impulsivitiy” showed evidence of genetic influence. A likely genetic influence was also demonstrated over peripheral vasoconstriction, blood pressure (systolic and diastolic) as well as plasma growth hormone level during and after a stressful interview but not during rest. Heart rate was demonstrated to be under genetic influence both at rest and during interview.     

Immunoglobulin-producing cells in CSF and blood from patients with multiple sclerosis and other inflammatory neurological diseases enumerated by Protein-A plaque assay

Using the Protein-A plaque assay, numbers of IgG + IgA + IgM producing cells determined in patients with multiple sclerosis (MS) were 0.1–5% in CSF and 0.1–0.7% in peripheral blood; interestingly, 7 of 11 MS patients had IgM producing cells in CSF. In patients with aseptic meningitis (AM), the corresponding values were 0.04–7.5% in CSF and 0.4–2.4% in peripheral blood. There were more Ig producing cells in peripheral blood from patients with AM and MS than in healthy subjects. cocorrelation between numbers of IgG producing cells in CSF and the concentrations of intrathecally produced IgG (CSF IgG index) was registered in patients with AM: the same was true for IgA. The Protein-A plaque method, adopted for 20 × 10³ lymphocytes, makes possible enumeration of Ig-producing cells in CSF and discrimination among cells secreting different Ig classes, thereby being a powerful tool for studying immune reactions in the CNS-CSF compartment.     

IgM and IgG responses during chronic relapsing experimental allergic encephalomyelitis (r-EAE)

During chronic relapsing experimental allergic encephalomyelitis (r-EAE) in guinea pigs, serum IgM and IgG concentrations increased markedly early in disease. Serum IgM and IgG increased similarly in control animals immunized with Freund's incomplete adjuvant (FIA) and Mycobacterium tuberculosis (MT). In the chronic phase of r-EAE but not in control animals, elevated IgM was also found in central nervous system (CNS) extracts, suggesting intrathecal IgM synthesis. IgG antibodies against myelin and myelin basic protein (MBP) were regularly detected in r-EAE sera from day 21 post inoculation (p.i.), reaching maximum levels in the early chronic phase. IgG antibodies against galactocerebroside (GC) and galactose appeared in some r-EAE sera. Oligoclonal IgG bands were demonstrated in all r-EAE guinea pig sera 21-26 days p.i. The bands in serum decreased in number and strength in the chronic phase. They could be traced to antibodies against MT in 4 of 10 animals, but not to antibodies against myelin, MBP, GC or galactose. Oligoclonal IgG bands were also regularly visualized in r-EAE CNS 124 days p.i., suggesting persistent intrathecal IgG synthesis. They varied in number and migration between different regions of individual CNS. Oligoclonal CNS IgG was related to antibodies against MT in only one of 7 animals, and in no case to antibodies against myelin.     

Cerebrospinal fluid specific proteins in multiinfarct and senile dementia

Cerebrospinal fluid (CSF) from patients suffering from senile dementia (SD) and multiinfarct dementia (MID) was fractionated into CSF-specific and antigenically serum-like proteins, using affinity chromatography with antihuman serum antibodies. The samples were isoelectric focused. Protein patterns were compared to similarly treated CSF from patients suffering from transient ischemic attacks (TIA), or normal volunteers. Characteristic changes were found in the CSF-specific protein pattern from SD patients.     

Virus-induced demyelination in herpes simplex virus-infected mice

Herpes simplex virus (HSV) infection of the mouse trigeminal ganglia and the brain stem is associated with demyelination of axons in the central part of the trigeminal root and inflammatory cell infiltration and perivascular demyelination in the brain stem. Cyclophosphamide (CPA) treatment prior to or soon after HSV inoculation caused increased axonal spread of infective virus from the peripheral site of inoculation, more widespread and severe demyelination and increased mortality, suggesting that by CPA the virus invasion of the CNS was facilitated. A direct cytocidal effect of HSV on myelinating cells seemed one plausible explanation for the demyelination. Influence on demyelination at late stages of infection by cytotoxic immune reactions are not excluded by the results reported but seemed not to dominate the picture. Schwann cells from the peripheral part of the nerve root invaded demyelinated areas in the brain stem and remyelinated the axons.     

Sarcoplasmic bodies in distal myopathy compared with nemaline rods

Sarcoplasmic bodies in a late onset distal myopathy and rods in nemaline myopathy have been investigated by electron probe X-ray microanalysis correlated to light microscopy. Sarcoplasmic bodies were glassy, drop-shaped structures up to 10 microns of length and easily distinguished in the scanning mode of electron microscopy performed on thick freeze-dried cryosections. They were found to be source of X-ray spectra characterized by a high sulfur peak. On semithin epoxy sections the sarcoplasmic bodies were observed in the scanning transmission mode as electron-dense structures which, according to X-ray microanalysis, exhibited a high sulphur and osmium content, possibly indicating the presence of sulphydryl groups. The nemaline rods were of 3 different types as judged by their light-microscopical appearance. They were, however, not visible in the scanning mode of electron microscopy performed on freeze-dried unstained cryosections. There were small differences in the elemental composition between different rods within the same biopsy but these were not systematically related to the differences in morphological appearance.     

Ontogenesis and functional mechanisms of peripheral synapses: (Proceedings of the international meeting held in Paris, 26–28 September, 1979), by J. Taxi (ed.), xiv + 396 pages,Elsevier/North-Holland Biomedical Press,Amsterdam, 1980, US$ 59.00, Dfl 121.00

Following our earlier observations on increased plasma concentrations of lead in amyotrophic lateral sclerosis (ALS), the erythrocyte uptake of lead from plasma has been studied in vitro. Whole-blood from ALS patients and controls was incubated after the addition of lead (0.6 μmol/l whole-blood) and plasma lead concentrations were repeatedly determined. Incubation was continued until haemolysis developed. Fairly stable plasma lead concentrations were established at, on the average, 0.5–0.6 μmol/l after 10–30 min and persisted throughout the incubation with no significant difference between ALS- and control samples. Unexpectedly, it was also observed that haemolysis occurred significantly earlier in the ALS- than in the control samples. Plateau levels in plasma lead concentration of the same order as in the present experiments have been observed both in ALS- and control samples in previous experiments with the same technique, where the lead dose added was twice as high, and these plateau levels were about 10 times higher than those observed in vivo in ALS patients and controls. It is therefore suggested that the final plasma lead concentrations in vivo is established by factors other than the erythrocyte uptake and it is improbable that the differences between ALS patients and controls in plasma lead concentration are associated with differences in the degree of lead uptake by the red cells. The increased plasma lead concentrations in ALS patients may instead be caused by increased fragility of the erythrocytes, as manifested by the earlier occurrence of haemolysis in the present experiments. The observation of increased red cell fragility is, however, also of interest as a possible manifestation of a generalized membrane defect.     

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.     

Different types of antibrain antibodies in multiple sclerosis: Studies employing myelin-deficient mutants of mice

The presence of complement fixing IgG class antibrain antibodies is a distinctive feature of multiple sclerosis (MS). Only two of the several specificities of these antibodies are yet identified. Testing a number of MS sera and CSF samples against homogenates of brain from two myelin-deficient mouse mutants, Jimpy and Quaking, and their littermate controls confirmed the occurrence of antibrain antibodies directed against both myelin-associated and non-myelin antigens.     

Cardiovascular and electrodermal adjustments during a vigilance task in patients with borderline and established hypertension

We studied cardiovascular and noncardiovascular sympathetic nervous system (SNS) responses to a vigilance task in patients with borderline (BT) or established hypertension (HT). Twelve patients in each group and twelve normotensive controls (NT) were subjected to a signalled reaction-time (RT) task which included the presentation of a noxious 110 dB white noise contingent upon RT-performance at the end of a 30 sec foreperiod. During this foreperiod recordings were made of: systolic and diastolic blood pressures, heart rate, skin- and muscle-blood flows. Skin and muscle vascular resistances were calculated from mean blood pressure and regional blood flows. Skin conductance level, fluctuations and responses were recorded as noncardiovascular SNS-responses. Compared to NT both HT and BT had higher resting blood pressures, heart rate, skin- and muscle-vascular resistances. BT showed higher resting skin conductance levels than HT and NT who were not different from one another. During stimulation HT and BT evidenced pressor hyperreactivity compared to NT. The electrodermal effects did not parallel the cardiovascular ones. Skin conductance and cardiovascular variables were more closely related in NT than HT or BT. The presence of cardiovascular hyperreactivity together with the absence of noncardiovascular hyperreactivity in HT indicates heightened SNS-activity specific to the cardiovascular system and not part of generalized SNS-arousal. The similarity between HT and BT is consistent with the notion that the differences between BT and HT are quantitative rather than qualitative.     

Immunoglobulin elution from multiple sclerosis brain

Immunoglobulin (Ig) was eluted from multiple sclerosis (MS) brain tissue. Razor thin slices of white matter from 10 g of MS and control brains were washed with 5 liters of phosphate-buffered saline (PBS), then treated for 90 sec with acetic acid, pH 2.5, containing Pepstatin and epsilon-aminocaproic acid. The protein concentrations of the PBS washes and neutralized acid eluates were determined, and the eluates were assayed for Ig by competitive microradioimmunoassay using rabbit anti-human F(ab1)2. Successive PBS washes reduced extracellular protein to a very low level. Equivalent quantities of protein were recovered from 7 MS and 6 non-MS brain samples after PBS washing and acetic acid elution. However, the amount of protein needed for 50% inhibition of [125I]IgG binding to anti-human F(ab1)2 was significantly less in MS brain than in non-MS brain (P less 0.05). The Ig in brain eluates was present in the void volume of a DEAE cellulose column. The techniques described above facilitate the isolation and characterization of cell-surface Ig in MS brain.     

Differences between lymphocyte subsets of the cerebrospinal fluid in subacute sclerosing panencephalitis and acute aseptic meningitis

In CSF of patients with acute aseptic meningitis (AAM) an increase in the percentage of total and active T lymphocytes was observed, whereas in SSPE a decrease in T cells was noted. In SSPE there was the increase in the relative number of lymphocytes bearing "avid" FcIgG receptor and decrease in alpha-naphthyl nonspecific esterase-positive cells, but in AAM the cell proportions were not disturbed. The changes in the peripheral blood lymphocytes subsets were less evident. The results seem to suggest that in AAM there is a strong T response in CSF with well preserved proportions of T-cell subsets, while in SSPE a low T-cell level may be accompanied by disturbances in T-cell function.     

Postnatal emotional balance in women with and without antenatal fear of childbirth

Women in the later stages of pregnancy were identified as ‘suffering’ or ‘not suffering’ from fear of childbirth by means of a special questionnaire. The two samples were interviewed two months after delivery. Women with antenatal fear of childbirth were found to run an increased risk of sustaining severe emotional imbalance postnatally with possible implications on their relationship to the child.     

Axoplasmic transport in vagal afferent fibres in normal and alloxan-diabetic rabbits

Fast and slow components of anterograde axoplasmic transport have been studied in the sensory fibres of the vagus nerve of alloxan-diabetic rabbits and age-matched controls by incorporation of tritiated leucine into nodose ganglion cells. The diabetic rabbits were maintained for 2 months with blood glucose levels in the range 20--40 mmol/l. They showed growth retardation and one third developed cataracts. No alteration of either fast or slow axoplasmic transport was detected in the diabetic animals. These results are discussed in the light of the present understanding of the role of axoplasmic transport, of the findings in other axoplasmic transport studies, and of other data available on the pathogenesis of human and experimental diabetic neuropathy.     

Enzyme release from isolated erythrocytes and lymphocytes in Duchenne muscular dystrophy

The release of lactate dehydrogenase (LDH) was studied in erythrocytes and lymphocytes from patients with Duchenne muscular dystrophy. Erythrocytes were incubated in Krebs-Ringer with or without 30 mM adenosine and in autologous plasma. There was little release of enzyme in Krebs-Ringer solutions up to 24 h or in autologous plasma up to 48 h, with no statistical difference between Duchenne patients and controls. Addition of 30 mM adenosine reduced the release of LDH in Duchenne erythrocytes at 48 h from 32.4 ± 5.66% (SE) to 6.2 ± 1.76% (P < 0.05) and in controls from 38.1 ± 5.93% to 23.5 ± 4.63% (n.s.). Lymphocytes incubated in Krebs-Ringer containing 33 mM glucose released LDH faster than Duchenne patients and controls. The adenosine effect could be due to abnormal adenosine uptake (because of a generalized membrane defect) or indicate intrinsic differences in the adenine nucleotide metabolism.     

Factor VIII related antigen, antithrombin III, spontaneous platelet aggregation and plasminogen activator in ischemic cerebrovascular disease: a study of stroke before 55.

In 52 patients under the age of 55 with verified ischemic cerebrovascular disease parameters of blood coagulation, platelet function and fibrinolysis were measured at a stage after the onset of disease when the acute phase reactions are presumed to have elapsed. The total material was compared to a control material of healthy men and women of corresponding age.Factor VIII related antigen was normal whereas antithrombin III was elevated. Subdivision of 36 of the patients on the basis of atherosclerotic evidence at angiography revealed that factor VIII related antigen and antithrombin III was elevated in the atherosclerotic group which probably reflects endothelial damage but possibly could have pathogenetic relevance.Platelet function was normal but showed a trend towards diminished activity in the atherosclerotic group. Our study gives support to the view that the platelet hyperreactivity reported by several investigators is an acute phase finding only, without pathogenetic relevance.Fibrinolytic insufficiency was recognized in 70% of the patients (independently of atheromatosis) which supports earlier investigations. The cause is probably an abnormality in the release of plasminogen activator from the endothelium as 7 of 8 abnormal cases tested by a histochemical method showed a normal content of activator in the vessel wall. Long term prospective studies are urgently needed.     

Lymphocyte subpopulations in multiple sclerosis: serial studies and clinical correlations.

Total lymphocyte counts and T and SIg+ cell numbers in peripheral blood were determined in 74 healthy controls and 44 MS patients. Twenty-five patients were studied in relapse and at two intervals after ACTH. Nineteen had not relapsed for 6 months but most had progressed clinically. MS patients showed significantly lower total lymphocyte counts which were not correlated with disease activity. Subpopulation analyses showed the MS patients to have significantly lower T cell numbers and significantly elevated SIg+ cell numbers and percentages. Although T cell numbers were low in all phases, both T and SIg+ cell abnormalities were maximal in progressive disease or in the recovery phase after relapse and a significant fall in T cell percentage and rise in SIg+ cell number was confirmed in serial studies of 16 patients followed from relapse to recovery. SIg+ cell numbers correlated negatively with relapse rate and correlated positively with the ratio of disability to number of relapses. The incidence in MS patients of HLA A3 was significantly increased and of HLA B12 and HLA BW40 significantly decreased but no correlation was seen between HLA phenotype and T, SIg+ or total lymphocyte counts. It is suggested that the peripheral blood SIg+ cell abnormalities and some of the T cell abnormalities are secondary to the pathological process, perhaps due to antigenic stimulation and particularly in non-relapsing progressive disease. Their possible role in influencing recovery or progression is discussed.     

Computerized tomography of brain and optic nerve in multiple sclerosis: Observations in 100 patients,including serial studies in 16

Computerized tomography (CT) of the brain was carried out in 100 patients with established or suspected multiple sclerosis (MS). The optic nerves were also examined in 53 of these patients. Areas compatible with demyelinating lesions were found in the cerebral hemisphere white matter and less frequently in the brain stem in 47% of cases. The hemisphere lesions were commonly multiple, typically situated in the deep white matter and periventricular regions, and were often asymptomatic. Small areas with unduly low attenuation coefficients were found in one or both optic nerves in 52% of patients in whom the optic nerves were examined. While these areas may represent demyelinating lesions their significance remains uncertain in view of poor correlation with clinical and electrophysiological parameters of optic nerve damage. Cerebral cortical atrophy and/or ventricular dilatation was found in 44% of cases, the frequency and severity of atrophy increasing with age and duration of disease.Serial studies after intervals of up to 21 months were performed in 16 patients, providing the opportunity to study the natural history of the cerebral lesions. While in some cases no significant change occurred, in others white matter lesions underwent an increase, or a reduction in size, and in some cases new lesions appeared. In some patients minor degrees of atrophy became apparent over the period of the study.The value of CT in the investigation of patients with suspected MS and as a means of studying the natural history of the disease is discussed.     

Viral antibodies in oligoclonal and polyclonal IgG synthesized within the central nervous system over the course of mumps meningitis

The occurrence of viral antibodies in relation to IgG separated by thin-layer polyacrylamide gel isoelectric focusing was studied in CSF and serum from 24 patients with mumps meningitis by immunofixation with viral antigens and autoradiography. Eleven of the patients displayed on the autoradiograms evidence of locally in the central nervous system synthesized mumps virus antibodies which were related to oligoclonal IgG bands in all 5 patients who displayed this CSF abnormality, otherwise to polyclonal IgG bands. Local synthesis of mumps virus antibodies was detectable in 43% of specimens obtained 1–13 days after onset, and in 75% obtained 27–47 days after onset. Only one patient displayed local synthesis of antibodies to other viruses (measles and herpes simplex) which could then be traced to polyclonal IgG bands.     

Functional inhibition and release: unilateral tachistoscopic performance and stereoelectroencephalographic activity in a case with left limbic status epilepticus

During prolonged nonconvulsive unilateral left limbic status epilepticus, a natural model of functional hemispheric inhibition, we performed two tachistoscopic experiments, a lexical decision task associated with a RVF (left hemisphere) superiority and a facial matching task associated with a LVF (right hemisphere) superiority. We found that epileptic activity in the left hemisphere, especially rhythmic high-frequency "tonic" discharges, inhibited performance on the lexical task but not on the facial matching task. This suggests that only cognitive activity in the discharging hemisphere is inhibited. Strikingly, the best performance of the right hemisphere was obtained while the left hemisphere was most inhibited, suggesting a functional balance of inhibition and release.