THE SPIROCHETE AND MULTIPLE SCLEROSIS

Cultures on anaerobic medium were made of the spinal fluids of 27 patients with multiple sclerosis and 13 controls after the method described recently by Ichelson. Where Ichelson found organisms resembling spirochetes in 78 per cent of patients with multiple sclerosis, we found some form of what appeared to be a living micro-organism in 18.5 per cent. The control fluids were all sterile. The work requires confirmation and amplification.     

HISTAMINE TREATMENT OF MULTIPLE SCLEROSIS

Histamine was administered intravenously or by iontophoresis to 19 patients with clearly established diagnosis of multiple sclerosis. In each of the three classifications of the disease (stationary, progressive, acute), no significant difference in improvement between treated and control groups was observed. (Controls were recorded cases in which treatment was identical except for histamine therapy.)In four of seven cases of progressive disease further deterioration occurred despite histamine therapy. Of the other three patients one died a year later and another returned to hospital in three months with severe symptoms which were not relieved on further histamine treatment.In two patients with remittent disease new symptoms (presumably caused by new lesions of the central nervous system) developed while histamine therapy was in progress.In cases of stationary disease histamine treatment was of no benefit.Reports are given of six typical cases in which histamine treatment was used.     

THE ALLERGIC ASPECTS OF MULTIPLE SCLEROSIS

For the past ten years there has been an increasing acceptance of the theory that allergenic reaction is a causative factor in multiple sclerosis. In the study of a series of patients the author traced many attacks directly to allergenic insults. When the offending substances were removed, a quiescent period often ensued. The severest symptoms of multiple sclerosis were most often associated with food allergens, the moderately severe with molds and fungi and the least severe with pollens and chemical offenders.The earlier the diagnosis and the beginning of treatment, the better the chance of arresting the disease and preventing serious crippling conditions. In cases of longer duration where the patient has become crippled or bedridden, physical therapy with relaxing medication is of great value.     

sICAM-1在多发性硬化症发病机制中的作用探讨

目的：探讨可溶性粘附分子－1（sICAM-1）在多发性硬化症发病机制中的作用。方法：用ELISA（双抗体夹心法）检测15例未经治疗的多发性硬化症患者血清中sICAM-1的水平,以15例正常人作对照。结果：患者血清中sICAM-1水平显著高于正常对照组（P＜0．01）;复发期患者sICAM-1水平显著高于缓解期。结论：sICAM-1可能是中枢神经系统急性炎症的标志之一;血清中sICAM-1水平的测定对临床诊断,预测复发具有一定意义。     

A THIOL PROTEINASE HIGHLY ELEVATED IN AND AROUND THE PLAQUES OF MULTIPLE SCLEROSIS

A thiol dependent proteolytic enzyme (tentatively identified as carboxypeptidase B) which liberates phenylalanine from CBZ-glutamyl-phenylalanine at pH 5.3 was shown, by a sensitive micromethod, to be greatly increased in activity in and around MS plaques. These increases exceeded those of other hydrolases previously measured. Plaque tissue, on the basis of lipid-free dry weight, is up to 3-fold richer in this enzyme than control white matter, and most samples of apparently uninvolved MS white matter already show elevated activities. The enzyme is highly dependent on the presence of dithiothreitol. It is unaffected by diisopropyl fluorophosphate and pepstatin, but inhibited by iodoacetate and leupeptin. Macrophages or lymphocytic infiltrations in the tissue do not appear to be the main source of the enzyme. In conjunction with measurements of DNA, reflecting gliosis, invasion by hematogenom cells and proliferation of phagocytes as well as oligodendrocyte loss, and acid lipase-esterase, indicative of the survival or degeneration of oligodendrocytes, these results are interpreted as probably reflecting predominantly the activity of astrocytes. The incidental finding that most samples of unaffected white matter from MS patients contain more DNA per unit lipid free dry weight than average control white matter is considered significant in pointing to more widespread tissue changes independent of or preceding plaque formation.     

ALLERGIC ENCEPHALOMYELITIS AS AN EXPERIMENTAL MODEL FOR MULTIPLE SCLEROSIS

Proteins isolated from bovine spinal cord exhibit encephalitogenic activity. One of these proteins, of collagen type, was found to be homogeneous. This protein, however, is not considered to be the main encephalitogenic agent; other proteins with different physicochemical characteristics were found to possess higher activity.The use of these proteins will make it possible to study the allergic nature of the experimental disease and may lead to disclosure of the underlying mechanism of the pathological process not only in allergic encephalomyelitis but in multiple sclerosis.     

Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin: IMPLICATIONS FOR REMYELINATION IN MULTIPLE SCLEROSIS*

Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor, and the mechanisms by which CNTF expression could be increased in the brain are poorly understood. Acetylsalicylic acid (aspirin) is one of the most widely used analgesics. Interestingly, aspirin increased mRNA and protein expression of CNTF in primary mouse and human astrocytes in a dose- and time-dependent manner. Aspirin induced the activation of protein kinase A (PKA) but not protein kinase C (PKC). H-89, an inhibitor of PKA, abrogated aspirin-induced expression of CNTF. The activation of cAMP-response element-binding protein (CREB), but not NF-κB, by aspirin, the abrogation of aspirin-induced expression of CNTF by siRNA knockdown of CREB, the presence of a consensus cAMP-response element in the promoter of CNTF, and the recruitment of CREB and CREB-binding protein to the CNTF promoter by aspirin suggest that aspirin increases the expression of the Cntf gene via the activation of CREB. Furthermore, we demonstrate that aspirin-induced astroglial CNTF was also functionally active and that supernatants of aspirin-treated astrocytes of wild type, but not Cntf null, mice increased myelin-associated proteins in oligodendrocytes and protected oligodendrocytes from TNF-α insult. These results highlight a new and novel myelinogenic property of aspirin, which may be of benefit for multiple sclerosis and other demyelinating disorders.     

LOCALIZATION, SOLUBILIZATION AND PROPERTIES GANGLIOSIDE TRANSFERASES IN RAT BRAIN OF N-ACETYLGALACTOSAMINYL AND GALACTOSYL GANGLIOSIDE TRANSFERASES IN RAT BRAIN

Abstract— The subcellular distributions of UDP-N-acetylgalactosamine: G_M3 N-acetyl-galactosaminyl transferase and UDP-galactose: G_M2 galactosyl transferase, two enzymes involved in the biosynthesis of gangliosides, were determined in the 7-day-old rat brain by means of synaptosomal fractionation techniques. The enzymes were located on the synaptic membranes and appeared to be closely associated with gangliosides and acetylcholinesterase. Solubilization of the transferase enzymes from the microsomal particles was achieved and differed from the solubilization of acetylcholinesterase and of the total membrane protein. Competition studies suggest that the ^N-acetylgalactosaminyl transferase involved in the formation of G_M2 from G_M3 is different from the N-acetylgalactosaminyl transferase involved in the formation of GalNAoGal-Glc-ceramide from Gal-Glc-ceramide, whereas in contrast, both the formation of G_M1 from G_M2 and of Gal-GalNAc-Gal-Glcceramide from GalNAc-Gal-Glc-ceramide appear to be catalysed by the same galactosyl transferase.     

PROTEOLYTIC ACTIVITY AND BASIC PROTEIN LOSS IN AND AROUND MULTIPLE SCLEROSIS PLAQUES: COMBINED BIOCHEMICAL AND EIISTOCHEMICAL OBSERVATIONS

Abstract— This combined histochemical and biochemical study has shown that acid proteinase activity (PH 3.5) is increased around histologically-defined active plaques of multiple sclerosis (MS). Biochemical estimation showed that the enzyme is more active in most samples of 'normal' white matter in MS than in controls. A gradient of enzyme activity was observed: control white matter-white matter distant from plaqueclose white matter-edgsplaque. Both electrophoretic and histochemical techniques revealed a reduction or absence of basic (encephalitogenic) protein in the plaques. Electrophoresis showed a diminution of encephalitogenic protein outside some plaques. Phospholipids that remain on the base-line of thin-layer chromatoplates were shown to be predominantly phosphoinositides combined with encephalitogenic protein     

ABNORMALITIES OF SCROTAL CONTENTS IN CHILDREN

Disorders of the scrotal contents in infancy and childhood parallel fairly closely those found in adults and deserve equal consideration. Hydroceles, epididymitis, hernia and cryptorchism are the more common conditions, but injuries, torsion of the spermatic cord and malignant tumors also occur in this age group.Early, accurate diagnosis and definitive treatment increase the prospect for children with testicular disease to develop into healthy, fertile adults.     

THE ACTIVITY OF GANGLIOSIDE SIALIDASE IN THE DEVELOPING HUMAN BRAIN

—The development of ganglioside sialidase and of four different p-nitrophenyl glycosidases in human brain was investigated including both prenatal and postnatal periods. The developmental curve for sialidase was different from that of the other glycosidases. While p-nitrophenyl glycosidases showed high activities at an early stage of development (21 foetal weeks), and remained at about the same level, ganglioside sialidase was not detected before the foetal age of 15-20 weeks. The sialidase activity at term reached about half the adult level and there was a possible decrease in activity during the first year. The sialidase activity then increased, approaching the adult level at about the age of 5 years. The development of the ganglioside sialidase activity in human brain can be related to changes in the concentration of individual brain ganglioside components. The late maturation of the sialidase system in relation to other glycohydrolases is also discussed as a possible protective mechanism for sialic acid-containing compounds during the early period of development.     

AMYOTROPHIC LATERAL SCLEROSIS AMONG GUAMANIANS IN CALIFORNIA

Amyotrophic lateral sclerosis is known to be prevalent among the Chamorros or natives of Guam and the other Mariana Islands. In a survey of adult Chamorros who had been residing in California it was found that the prevalence was equally high among that group.Guamanians residing in California were found to eat diets similar to those of other Californians and to be living in housing which was similar to that of the other California populations of the same income status. A few native articles of food which were received occasionally by some of the Guamanians were not believed to be of etiologic significance in ALS.The data on the prevalence of ALS among the Guamanians in California suggested that change of environment from Guam to California does not prevent the disease in persons predisposed to it. The data support the view that ALS is due to a genetic mechanism.     

GANGLIOSIDE COMPOSITION AND BIOSYNTHESIS IN CULTURED CELLS DERIVED FROM CNS

Abstract— Cultured mouse neuroblastoma cells (clone N18) contained a homologous series of gangliosides, G_M3, G_M2, G_M1 and G_D1a; the total lipid bound sialic acid (LBSA) was 3.3 nmol per mg of protein, of which G_D1a comprised two-thirds. In contrast, neonatal hamster astrocytes (clone NN) and human glioblastoma cells (Cox clone) contained mainly G_M3, which represented 95% of the 2 nmol of LBSA per mg protein in these cells. When the cells were grown in the presence of [¹⁴C]galactose, label was incorporated into all of the gangliosides isolated from the cells. The labeling pattern corresponded to the ganglioside composition of the cell lines; G_D1a was more extensively labeled in N18 cells and G_M3 was the major labeled ganglioside extracted from glial cells. In addition to in rivo biosynthesis, in vitro synthesis of gangliosides was also determined. The activities of five glycosyltransferases of the ganglioside biosynthetic pathway were measured in homogenates of the three cell lines. The neuroblastoma cells contained all five enzyme activities whereas the two glial cell lines were deficient in UDP- N -acetylgalactosamine: G_M3 N -acetylgalactosaminyltransferase activity, which catalyzes the synthesis of G_M2 from G_M3. The results indicated that cells of neuronal origin contain the more complex gangliosides associated with CNS and the requisite biosynthetic enzymes and that cells of glial origin are missing these complex gangliosides and the key glycosyltransferase required for their synthesis.     

HISTOCHEMISTRY OF MYELIN. XIII DIGESTION OF BASIC PROTEIN OUTSIDE ACUTE PLAQUES OF MULTIPLE SCLEROSIS

Abstract— Plaques of multiple sclerosis from a patient with a short clinical history were investigated by qualitative and quantitative histochemical methods. One of three plaques examined showed perivenous lymphocytic infiltration; this plaque was regarded as a particularly early acute lesion. In this plaque a relatively wide zone of diminished staining for basic protein extended outwards around the edge of the lesion. A narrower and irregular zone of diminished cerebroside staining was also seen around the plaque. Staining for phosphoglycerides and cholesterol was relatively normal up to the edge of the lesion; no zone of reduced staining for these lipids was seen outside the plaque. Proteolytic activity was increased throughout the lesion (pH 3.5 > 7.4). The two less acute plaques showed no obvious loss of basic protein and cerebroside outside the plaque. Addendum: Two further acute plaques of multiple sclerosis obtained recently, showed a similar loss of basic protein outside of lesion.