K. B. Fraser

Increased tendency to spontaneous in-vitro lymphocyte transformation in clinically active multiple sclerosis.

Lymphocytes from 8 of 10 patients with clinically active multiple sclerosis (MS) but from only 3 of 18 patients with quiescent MS and 4 of 20 healthy donors transformed spontaneously on in-vitro culture. The transformed cells from all donors had the characteristics of B lymphocytes (surface and intracytoplasmic immunoglobulin and complement receptors) and carried antigens of Epstein-Barr virus. It is suggested that these results are further evidence that immunoregulation in active MS is abnormal.

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.

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.

Virus specific antibodies in multiple sclerosis.

The prevalence of the (8-thalassaemia trait was high in the sample examined. With a prevalence of 17-3% the birth ratz of homozygous /8-thalassaemia can be estimated to be 08%. A relative birth rate of 0-6% was also found among Cypriots in London.5 Considering the severity of thalassaemia major these figures demonstrate its seriousness as a public health problem in Cyprus. Since at present there is no other way of reducing the birth rate of patients with thalassaemia major except by genetic counselling, it is suggested that the whole population at risk should be screened for the thalassaemia trait and careful genetic counselling provided to all prospective couples wh2never both the prospective father and mother are heterozygous. On the other hand, the prevalance of clinical manifestations associated with G-6PD deficiency, namely, favism and severe neonatal jaundice, seems to be higher than that expected on the basis of the rather low prevalence of G-6-PD deficiency (5-2%).6 It should be noted in this respect that in addition to G-6-PD deficiency other unknown factors, probably genetic, may be responsible for precipitating clinical manifestations in sensitive individuals. Interestingly we found a relatively high prevalence of atypical ACAH; this is generally believed to be geographically distributed rather homogeneously with a prevalence of about 4%.7 The higher prevalence observed in this study (6-9%) may partly explain why a number of the first cases of suxamethonium apnoeas and some of the rare abnormal ACAH genotypes were described in Cypriots residing in England.We are, etc., CHRISTOS KATTAMIS STAVROS HAIDAS ANNA METAXOTOU-MAVROMATI NICOLAS MATSANIOTIS

Mycoplasmas in cell cultures from rheumatoid synovial membranes

Ten strains of myocoplasmas were recovered from cultures of synovium or cultures inoculated with synovial fragments from rheumatoid arthritis and one from osteo-arthritis. The source of the organisms is not known. Patients with rheumatoid arthritis had no complement-fixing antibody and no fluorescent staining antibody against the mycoplasmas isolated and no mycoplasma antigen was detected by immunofluorescence in sections of synovia and in synovial fluids.The strains isolated were of two main serological types and could be distinguished by direct fluorescent antibody staining from standard types of human commensals and the common tissue-culture contaminants. One may be Mycoplasma laidlawii.

Immunoelectron microscopic studies on haemagglutinin and haemolysin of measles virus in infected HEp2 cells.

The antigenic determinants of the haemagglutinin and haemolysin antigens of measles virus were located at the surface of HEp2 cells infected with measles virus and on measles virions released from these cells, using immunoelectron microscopy. Antisera specific for haemagglutinin or haemolysin antigen and peroxidase-conjugated antiglobulin were used. Treatment of the infected cells with trypsin removed the virus spikes and prevented binding by the anti-haemagglutinin serum, while the reaction with anti-haemolysin serum was unaltered. This suggests that the antigenic determinants for measles haemagglutinin reside on the spike, while the antigenic determinants for haemolysin reside on, or are close to, the virus membrane.

The Sensitivity of Measles Virus Haemolysin to Acetone and the Preparation of Mono-specific Human Anti-Haemolysin by Absorption

The haemolysin of measles virus, either in the virion or in infected cells, is functionally and antigenically sensitive to acetone. Absorption of human sera with acetone-treated, measles virus-infected cells removes antibodies to all measles virus structural antigens except haemolysin. The antibody titres of absorbed sera give good correlation in HLI, neutralization and fluorescent antibody staining on unfixed infected cells.

Recognition of host-membrane antigens in the envelope of measles virions

Trypsin- and acetone-treated virions from either of two strains of measles virus grown in Vero cells stimulated the production in guinea pigs of (i) virus-specific antibodies to polypeptide (P) of molecular weight 70,000 (70K) and to the portion of the HA spike embedded in the viral envelope, but not to M protein, and (ii) antibodies to two host cell membrane antigens which were identified as glycoproteins with molecular weights of 108K and 104K. These host cell antigens were present in increased amounts in infected cells and were intimately associated with the virus. Untreated measles virions grown in Vero cells also stimulated the production of antibody to the 108K glycoprotein. The host polypeptides were less antigenic in virus derived from HEp2 cells, which apparently contained less of these antigens.

Enzyme Treatment of Unfixed Cell Cultures as a Means of Determining Different Specificities .of Immunoglobulin-M in Multiple Sclerosis and Measles *

Treatment of measles virus-infected cells with phospholipase C or with proteases alters the fluorescent staining pattern subsequently produced by IgM from measles patients (measles-IgM) and by IgM from multiple sclerosis patients (MS-IgM).Receptors for measles-IgM appear to be more resistant to phospholipase C and less resistant to proteases than are these from MS-IgM. Specific attachment of both types of IgM is abolished by mild periodate treatment.The cell membrane becomes permeable to IgG and IgM when treated with phospholipases A, C or D or with lysolecithin. Such treatment and mild treatment with certain organic solvents produce aggregates which have an afrinity for IgM of undetermined specificity.

Herpes simplex and temporal lobe epilepsy.

The prevalence of the (8-thalassaemia trait was high in the sample examined. With a prevalence of 17-3% the birth ratz of homozygous /8-thalassaemia can be estimated to be 08%. A relative birth rate of 0-6% was also found among Cypriots in London.5 Considering the severity of thalassaemia major these figures demonstrate its seriousness as a public health problem in Cyprus. Since at present there is no other way of reducing the birth rate of patients with thalassaemia major except by genetic counselling, it is suggested that the whole population at risk should be screened for the thalassaemia trait and careful genetic counselling provided to all prospective couples wh2never both the prospective father and mother are heterozygous. On the other hand, the prevalance of clinical manifestations associated with G-6PD deficiency, namely, favism and severe neonatal jaundice, seems to be higher than that expected on the basis of the rather low prevalence of G-6-PD deficiency (5-2%).6 It should be noted in this respect that in addition to G-6-PD deficiency other unknown factors, probably genetic, may be responsible for precipitating clinical manifestations in sensitive individuals. Interestingly we found a relatively high prevalence of atypical ACAH; this is generally believed to be geographically distributed rather homogeneously with a prevalence of about 4%.7 The higher prevalence observed in this study (6-9%) may partly explain why a number of the first cases of suxamethonium apnoeas and some of the rare abnormal ACAH genotypes were described in Cypriots residing in England.We are, etc., CHRISTOS KATTAMIS STAVROS HAIDAS ANNA METAXOTOU-MAVROMATI NICOLAS MATSANIOTIS