Measles and Other Virus-specific Immunoglobulins in Multiple Sclerosis

Immunoglobulins M and G specific for meales, herpes simplex, and rubella viruses were assayed by the fluorescent antibody method in sera and cerebrospinal fluids (C.S.F.) obtained simultaneously from 30 patients with multiple sclerosis, 30 patients with other neurological diseases, and 30 “normal” control subjects. Sera of 11 out of 30 patients with multiple sclerosis had IgM which reacted specifically with measles virus-infected cells, compared with 2 out of 30 of the patients with other neurological diseases and none of the 30 normal controls. Virus-specific IgM was not found in C.S.F. by this method.The geometric mean titre of measles virus-specific IgG in serum was significantly higher in the multiple sclerosis group than in either control group, and while IgG specific for all three viruses was found in C.S.F., suggesting transfer across the blood-brain barrier, measles IgG predominated.     

Measles Virus-Specific IgG in Cerebrospinal Fluid in Multiple Sclerosis

The prevalence of measles virus-specific IgG in cerebrospinal fluid (C.S.F.) of patients with multiple sclerosis (M.S.) has been compared with that in fluids from patients with other neurological diseases and from normal control subjects. The prevalence in the three groups was 58·1%, 24·1%, and 0% respectively. Fivefold concentration of the specimens increased the prevalence in the first two groups to 80·6% and 34·5% respectively, while measles IgG was not detected in any fluids of the normal control group, even after concentration.     

Measles Virus Antibody in Cerebrospinal Fluids from Patients with Multiple Sclerosis

A strong measles-specific gel precipitation reaction was found in the cerebrospinal fluid (C.S.F.) of two patients with multiple sclerosis (M.S.) (total of 15 tested). The serum and C.S.F. specimens from these two patients were tested for measles antibody by six assay methods. The results were compared with those obtained from serum and C.S.F. specimens of a patient with subacute sclerosing panencephalitis (S.S.P.E.). The gel precipitation line produced by the C.S.F. from the M.S. patients was identical with one of the three lines produced by the C.S.F. from the S.S.P.E. patient. The main antigenic component responsible for measles antibody appearing in the C.S.F. of the S.S.P.E. patient and the M.S. patients was also electrophoretically similar, and the corresponding antibody was associated with IgG. The serum/C.S.F. antibody titre ratios with the various assay methods used suggest that the C.S.F. antibodies are mainly to other than envelope components of measles virus. No complement-fixing antibody against 27 other viruses or Mycoplasma pneumoniae was found in the C.S.F. of the two M.S. patients.     

Immunoglobulin M. Specific for Measles and Mumps in Multiple Sclerosis

Sera from 43 patients with multiple sclerosis were tested by immunofluorescence. Sera from patients with active multiple sclerosis included four with measles virus-specific immunoglobulin M (measles IgM) and two with mumps virus-specific IgM (mumps IgM). In one case each mumps IgM and measles IgM seem to have persisted for two and a half years and three years respectively. In a comparable group of 43 patients with other nervous diseases measles IgM was found in only one serum, and among 43 normal patients no measles or mumps IgM was found.Herpes simplex virus-specific IgM (herpes simplex IgM) was distributed among all three groups. Anticellular IgM was also found, predominantly in active multiple sclerosis, and persisted in two sera for two and a half years.     

Specific Laboratory Test for Diagnosis of Multiple Sclerosis

Lymphocytes from patients with multiple sclerosis are much more susceptible to the inhibitory activity of linoleic acid (0·08 mg/ml) when tested for sensitization to thyroid by the macrophage electrophoretic mobility test (91% inhibition) than are those from normal subjects (57% inhibition). Cells from patients with a variety of other neurological diseases give 47% inhibition with linoleic acid. These differences are specific for multiple sclerosis and can be used as an in-vitro diagnostic test for the disease. Nearly 43% of clinically normal near relatives of patients with multiple sclerosis show an “anomalous” figure of about 77%; in the remainder the figure is the same as in the general population (57%). An anomalous result is compatible with lifelong freedom from M.S. Possibly a congenital anomalous handling of unsaturated fatty acids is a constant feature of the disease.     

剪切应力诱导血小板聚集

剪切应力诱导血小板聚集（shear-induced platelet aggregation, SIPA）是指在高剪切流场诱导下血小板表面的膜糖蛋白（GPⅠb/Ⅸ/Ⅴ和GPⅡb/Ⅲa）与血浆中的von Willebrand因子（vWF）相结合,介导血小板的活化、黏附和聚集,是动脉血栓的重要成因.SIPA还需要Ca2+,ADP/ATP等生化因素的参与,因而SIPA现象是生化因素和力学因素偶合作用的结果.细胞外Ca2+是高剪切应力诱导血小板发生聚集的必需条件,Ca2+的跨膜内流引起细胞骨架结构的改变和GPⅡb/Ⅲa的活化.近来对ADP/ATP位于血小板膜上的P2受体的研究表明,P2受体与细胞内Ca2+协同作用通过多种生化途径调控血小板的活化过程在SIPA的信号传导中起着关键的作用.从力学环境与生化反应的偶合关系入手研究SIPA现象的触发机制,深入研究SIPA现象中的信号转导通路是今后的研究热点之一.     

Non-specificity of Laboratory Test for Diagnosis of Multiple Sclerosis

It has been claimed that the inhibiting effect of linoleic acid on the macrophage electrophoretic mobility test provides a specific laboratory method for the diagnosis of multiple sclerosis (M.S.) and may also enable susceptible relatives of M.S. patients to be identified. Three trials of the method under double-blind conditions have failed to confirm that the test is diagnostically useful.     

Poor Sleep in Patients with Multiple Sclerosis

Background

Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). Sleep may be influenced by MS-related symptoms and adverse effects from immunotherapy and symptomatic medications. We aimed to study the prevalence of poor sleep and the influence of socio-demographic and clinical factors on sleep quality in MS- patients.

Methods

A total of 90 MS patients and 108 sex-and age- matched controls were included in a questionnaire survey. Sleep complaints were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a global PSQI score was used to separate good sleepers (≤5) from poor sleepers (>5). Excessive daytime sleepiness, the use of immunotherapy and antidepressant drugs, symptoms of pain, depression, fatigue and MS-specific health related quality of life were registered. Results were compared between patients and controls and between good and poor sleepers among MS patients.

Results

MS patients reported a higher mean global PSQI score than controls (8.6 vs. 6.3, p = 0.001), and 67.1% of the MS patients compared to 43.9% of the controls (p = 0.002) were poor sleepers. Pain (p = 0.02), fatigue (p = 0.001), depression (p = 0.01) and female gender (p = 0.04) were associated with sleep disturbance. Multivariate analyses showed that female gender (p = 0.02), use of immunotherapy (p = 005) and a high psychological burden of MS (p = 0.001) were associated with poor sleep among MS patients.

Conclusions

Poor sleep is common in patients with MS. Early identification and treatment of modifiable risk factors may improve sleep and quality of life in MS.     

Lymphocyte Sensitization to Carcinoembryonic Antigen (Gold) With Special Reference to Multiple Sclerosis

Lymphocytes from patients with multiple sclerosis are sensitized to carcinoembryonic antigen (C.E.A.) in almost the same degree as are those from subjects with cancer. During pregnancy and the early puerperium there is an even higher degree of cellular sensitization to C.E.A. Patients with neurological diseases other than multiple sclerosis also show significant sensitization to C.E.A. though of less degree than do those with multiple sclerosis. Sensitization to C.E.A. is thus not specifically characteristic of cancer. The unexpected sensitization in multiple sclerosis may be associated with the pronounced degree of gliosis found in that condition.     

Circadian Variations in Blood Coagulation Parameters, Alpha-Antitrypsin Antigen and Platelet Aggregation and Retention in Clinically Healthy Subjects

Ten clinically healthy subjects (5 men and 5 women), 31 11 yrs of age, were studied at six timepoints (0800, 1200, 1600, 2000, 0000, 0400) distributed over a 1-week span. Circadian rhythms in platelet aggregation in response to adenosine diphosphate (ADP) and adrenalin (A), platelet adhesiveness measured as retention in a glass bead column, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, Factor VIII activity and alpha-1-antitrypsin antigen showed circadian rhythms. The plasma concentrations of plasminogen, alpha-2-macroglobulin, and antithrombin III (AT III) antigen, Factor V and fibrinogen degradation products showed no circadian rhythm by ANOVA or cosinor analysis. The phase relations of the rhythms of different coagulation parameters are of interest in the physiology and pathobiology of the coagulation-fibrinolytic system. The extent of the circadian rhythm (range of change) described is not of a magnitude to lead to diagnostic problems in the clinical laboratory. The timing of these rhythms, however, may determine transient risk states for thromboembolic phenomena, including myocardial infarction and stroke. Several but not all coagulation parameters suggest a transient state of hypercoagulability during the morning hours. The recognition of these rhythmic, and thus in the time of the occurrence predictable temporary risk states for thromboembolic phenomena, may lead to timed treatment and/or effective prevention.     

Coumarin Therapy and Platelet Aggregation

Platelet aggregation has been related to blood coagulation studies in patients on nicoumalone, a coumarin anticoagulant. Aggregation studies were performed by means of Chandler''s tube and the adenosine diphosphate (A.D.P.)-induced optical density method. Platelet aggregation in Chandler''s tube has been shown to be quite different from A.D.P. aggregation and to be dependent on the “intrinsic” (blood) clotting system. When the intrinsic system was depressed by coumarin anticoagulant, aggregation was delayed in Chandler''s tube, but patients with a predominantly “extrinsic” (tissue) system defect gave normal results even when their prothrombin time was excessively prolonged. In contrast there was an increased response to A.D.P. in the anticoagulated patients.The study emphasizes the different mechanisms of platelet aggregation, which we have referred to as coagulation-induced and A.D.P.-induced aggregation. It also shows the limitations of routine control of oral anticoagulants by prothrombin time alone, as the coagulation-induced platelet aggregation appears to be quantitatively related to the overall level of clotting factors in the intrinsic system and independent of the extrinsic system.     

Cigarette Smoking and Platelet Aggregation

The influence of cigarette smoking on platelet aggregation was studied in habitual and non-habitual smokers. The results indicate that habitual smokers have a greater tendency to platelet aggregation than do non-habitual smokers. Acute effects of cigarette smoking were, however, not significant. The nucleotide content and the serotonin content of the platelets were analyzed. The adenosine nucleotide and serotonin contents were similar in smokers and non-smokers in the control state and neither showed significant changes on cigarette smoking. There were significant correlations between the control concentrations of the various nucleotides in both groups and there were even higher correlations after smoking. Platelet aggregation bore no demonstrable relationship to the nucleotide or serotonin contents of the platelet. We conclude that the long-term effect of smoking is probably more important than the acute effect.     

Immunoperoxidase Stain of Measles Antigen in Tissue Culture

A specific electron microscopy staining technique for measles antigen has been developed by using Vero cells infected with a subacute sclerosing panencephalitis (SSPE) measles virus strain and fixed in glutaraldehyde or formaldehyde. Peroxidase-labeled antibody was prepared according to the method of Avrameas (4). Sera from SSPE patients with high measles antibody titer as well as normal human sera with and without measles antibody were used. With both fixatives, specific labeling was obtained on the surface of infected cells, on the budding site, and on complete viral particles. The cell membrane staining sometimes had a patchy distribution in that the reaction was most intense on the surface projections in front of each nucleocapsid. This suggests modification of the cell membrane in association with the nucleocapsids. In contrast, no label was detected on the membranes of the cells during the latent period from penetration through maturation of the virus. In formaldehyde-fixed cultures, cytoplasmic inclusions were stained, and this label was located on the "fuzzy" material around the nucleocapsids. The smooth type of nucleocapsids, mainly seen in the nucleus, were never labeled. These findings suggest that the antigenic nature of the "fuzzy" nucleocapsids in the cytoplasm may be different from that of the "smooth" nucleocapsids. The immunoperoxidase method gives good resolution of viral antigenic sites at high magnifications under electron microscopy and may be of value in studies on the immunopathogenesis of SSPE and other chronic viral infections.     

Nutrition Facts in Multiple Sclerosis

The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.     

Tumefactive Multiple Sclerosis in Taiwan

Background

Multiple sclerosis (MS) is less common in Asia, including Taiwan, and some characteristics of MS in Asians differ from those of Caucasians. Tumefactive brain lesion is even rarer in MS patients.

Objective

To review patients with tumefactive MS and compare them with those in other studies investigating tumefactive demyelinating lesions and our Taiwanese typical MS patients.

Methods

Twelve patients (6.3%) from the 190 MS patients visiting Taipei Veterans General Hospital from 1985 to 2010 were enrolled. They all fulfilled the McDonald or Poser criteria for MS and had at least one brain lesion larger than 2 centimeters with or without a mass effect.

Results

Eleven patients (91.7%) were female and presented tumefactive brain lesions during the first attack. The clinical course of all patients was relapsing-remitting with a second attack within 2 years. Their initial extended disability status score was higher, but the prognosis was better after more than 2 years of follow-up, than in other studies. Moreover, our patients did not have optic or spinal involvement as well as positive neuromyelitis optica immunoglobulin or aquaporin-4 antibody, which is very common in Taiwanese MS patients.

Conclusion

Tumefactive MS is not common in Taiwan. Although the tumefactive demyelinating lesions seem to be terrible initially, their prognosis is relatively more favorable than expected.