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Biomedical subjects

H Moser

Publications and source records attributed to H Moser.

At least 127 records · Page 7Linked to original sources

The quantification of the haemagglutinin content of influenza whole virus and Tween-ether split vaccines.

Monovalent whole virus and Tween-ether split vaccines prepared from influenza A/Bangkok, A/Brazil and B/Singapore were assayed for haemagglutinin content using single radial immunodiffusion (SRID), quantitative sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunization of guinea pigs. When SRID was performed with split vaccines, haemagglutinin values were consistently recorded which were in the range of 50 to 25% of the values obtained before disruption of virions. When, however, disruption was conducted in the presence of excess detergent, thus preventing aggregate formation of solubilized haemagglutinin, test values comparable with those of whole virus vaccines were obtained. In agreement with these results, immunization experiments revealed that whole virus and corresponding split vaccines exhibited comparable immunogenicity in guinea pigs. Additionally it could be calculated from SDS-PAGE and densitometer tracings, obtained by scanning the gels after staining with either Coomassie blue or FITC-Con A, that 90 to 95% of whole virus HA2 was recovered in Tween-ether split vaccines. On the basis of these findings we conclude that precise quantification of Tween-ether split vaccines is not possible by the SRID test alone. As aggregate formation of solubilized haemagglutinin occurs, we suggest that either a physico-chemical method including a disaggregation procedure, such as SDS treatment, or immunological evaluation of the original whole virus preparation before disruption of virions should be applied as an additional criterion for quantification of influenza Tween-ether split vaccines.

Animals↗

Comparison of effects of adjuvants on efficacy of virion envelope herpes simplex virus vaccine against labial infection of BALB/c mice.

A subunit virion envelope vaccine of herpes simplex virus type 1 was evaluated for its ability to protect labially infected mice from development of the primary herpetic lesion, encephalitic death, and latent virus infection in the trigeminal ganglion. Several adjuvants, including aluminum hydroxide and polyriboinosinic acid-polyribocytidylic acid complexed with poly-L-lysine and carboxymethyl cellulose were investigated for their ability to enhance protection of the subunit vaccine and were compared in effectiveness with complete Freund adjuvant. The subunit vaccine was demonstrated to be immunogenic, as shown by development of antibody detectable by an enzyme-linked immunosorbent assay. The humoral immune response was correlated with protection from herpetic encephalitis and, at a lower degree, with prevention of the appearance of primary herpetic lesions and acceleration of lesion resolution. The efficacy of the vaccine was most apparent in protecting mice from encephalitic death. To reduce or prevent the development of latent infection was most difficult, but was achieved with some vaccine regimens. Repeated administrations of vaccine with adjuvant were required for this protection. The most effective adjuvant was complete Freund adjuvant, but several synthetic adjuvants were effective, particularly aluminum hydroxide and the polyriboinosinic-polyribocytidylic acid-poly-L-lysine-carboxymethyl cellulose immunoadjuvant.

Adjuvants, Immunologic↗

A comparative study of digoxin levels by radioimmunoassay micromethod in capillary and venous blood samples in children.

In a group of 30 digitalized children, we compared the digoxin levels in capillary and venous plasma samples, both of which were obtained simultaneously from each child. We statistically concluded that the venous plasma samples could surely be replaced by capillary plasma samples for measurements of plasma digoxin levels without any significant difference. Additionally, we showed that storing the capillary plasma samples at room temperature for 3 days did not lead to any significant change in digoxin levels. This is an important point for the hospitals and practitioners who do not have their own possibilities for digoxin determination.

Blood Preservation↗

Congenital nephrotic syndrome: clinico-pathological heterogeneity and prenatal diagnosis.

During the last five years, we have observed four families in which siblings were affected with the congenital nephrotic syndrome (CN). Clinically, all patients, with one exception, could barely be differentiated from classical examples of CN of the Finnish Type (CNF). Morphologically, however, each family showed a different type of CN, although the appearance in siblings was identical. This morphological heterogeneity, makes it likely that CN in a population outside Finland is the result of an unknown number of autosomal recessive mutations at different gene loci. In an attempt to diagnose CN prenatally by means of measurements of the concentration of alpha-fetoprotein in amniotic fluid, we found two false normal results, one in a patient with histologically confirmed CNF, another in a patient with CN, histologically non Finnish Type. Thus the results of prenatal diagnostic procedures for these disorders have to be reevaluated.

Child, Preschool↗

Herpes simplex virus subunit vaccine: characterization of the virus strain used and testing of the vaccine.

Herpes simplex virus type 1 (HSV-1) used for vaccine production was isolated from a nasal recurrent infection and propagated over a limited number of passages in human diploid cells only. It was designated as HSV-1 BW3 and has been characterized by neutralizing antibodies as a typical HSV type 1 strain. In vitro transformation studies performed with this isolate in mouse or hamster cells revealed only very low, if any, transforming capacity. A preparation of HSV-1 BW3 which can be used as seed lot for vaccine production has been proven to be free of any adventitious agents such as bacteria, fungi mycoplasma or viruses other than HSV-1 BW3. An envelope antigen (EAG) preparation was obtained from purified HSV-1 particles. It was free of detectable viral DNA and could be proven to be efficacious in mouse models against challenge infections with either HSV-1 or HSV-2. The potency of the vaccine was greatly enhanced by the addition of poly-inosinic-poly-cytidylic acid complexed with poly L-lysine and carboxymethylcellulose (PICLC) as adjuvant. A single vaccine dose was sufficient to protect mice from morbidity and the fatal outcome of HSV infection, but not from the establishment of latency. Persistent ganglionic infections could be, however, significantly reduced by repeated administration of the vaccine before primary infection.

Adult↗

Incomplete trisomy 22. I. Familial 11/22 translocation with 3:1 meiotic disjunction. Delineation of a common clinical picture and report of nine new cases from six families.

A syndrome due to 3:1 meiotic segregation of balanced 11/22 translocation is defined from nine personally observed patients and 22 cases from the literature with apparently the same aberration. Frequent findings include a characteristic face with deep-set eyes, flat nose, prominent upper lip, receding mandible and preauricular pits or tags, male genital hypoplasia, anal atresia or other anomalies of the anus, cleft palate, and congenital heart defect. Less frequent are severe reduction of the auricles, an additional pair of ribs, and hypoplasia of the diaphragm. Perinatal mortality is high. Growth is usually and psychomotor development is invariably and severely delayed. Balanced 11/22 translocations are apparently disproportionally frequent; as the balanced rearrangement is not easy to detect, it is important to be aware of it at the family investigation of cases with extra chromosomes similar to a No. 22 or 22q-. The unbalanced products are most probably trisomic for both a segment of 22 (22q-) and a distal segment of 11q; the exact determination of the breakpoints is not possible at present due to the similar banding characteristics of the two segments involved in the translocation.

Abnormalities, Multiple↗

Efficacy of a virion envelope herpes simplex virus vaccine against experimental skin infections in hairless mice.

Hairless mice were immunized with herpes simplex virus type 1 (HSV-1) envelope antigen (EAG), EAG in association with polyriboinosinic . polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose (PICLC), and inactivated purified HSV-1 (VAG). After 2 weeks the mice were challenged by a percutaneous HSV-1 infection in the orofacial (OF) or lumbosacral (LS) skin area. Following immunization a consistent cell-mediated immune response was observed in all immunized mice, although the humoral immune response was very low, or not detectable. After challenge, a marked secondary humoral and cell-mediated immune response developed in all immunized mice, and the animals were protected against the development of skin lesions and the fatal outcome of infection. However, the establishment of latent infections in the sensory ganglia was not prevented by the immunization procedure.

Animals↗

Protectivity of herpes simplex virus antigens: studies in mice on the adjuvant effect of PICLC and on the dependence of protection on T cell competence.

The efficacy of a herpes simplex virus type 1 (HSV-1) envelope antigen (EAG) preparation against HSV infection was studied in T cell competent and T cell deficient mice. Immuno-competent mice were successfully protected against herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) infection when immunized 2 weeks prior to this infection with a heat-inactivated whole virus preparation or a HSV-1 envelope antigen (HSV-1 EAG) preparation. Since HSV-1 EAG was considerably less effective than the whole virus preparation, a poly.riboinosinic-poly.ribocytidylic acid complex with poly-L-lysine and carboxymethylcellulose (PICLC) was used as adjuvant. Immunization with HSV-1 EAG plus PICLC resulted in a pronounced increase of this protection rate as compared with that obtained after immunization solely with HSV-1 EAG. PICLC alone, however, offered no protection when given 2 weeks before challenge. In T cell deficient nu/nu mice no protection was achieved with HSV-1 EAG while their T cell competent, heterozygous littermates were protected. From these results it may be concluded that T cell competence is a prerequisite for establishing a protective immunity against HSV infection after immunization with HSV-1 EAG.

Adjuvants, Immunologic↗

Correlation of herpes simplex virus antibody titers and specific lymphocyte stimulation in adult blood donors.

Antibody titers to herpes simplex virus type 1 in sera from healthy adult donors were assayed by complement fixation, microneutralization, and an enzyme immunoassay (ELISA). This last test proved to be the most sensitive method for antibody detection. It was estimated that ELISA antibody titers were up to 40-fold higher than neutralizing antibody titers and up to 100-fold higher than complement fixation antibody titers. Due to the higher sensitivity of ELISA, only 3 of 36 blood donors tested in this assay were shown to be seronegative, whereas 6 additional persons of the same group were termed seronegative by the microneutralization assay. Furthermore, four of the latter also did not respond in the complement fixation test. In vitro stimulation of peripheral lymphocytes by using a partially purified herpes simplex virus type 1 particle antigen was achieved for all seropositive blood donors. Only those three donors who were ELISA negative reacted negatively in this stimulation assay. From these results it may be concluded that ELISA is an appropriate method not only for rapid and sensitive antibody determination but also for selecting herpes simplex virus-negative patients.

Adult↗

Abnormal growth kinetics and 5'-nucleotidase activities in cultured skin fibroblasts from patients with Duchenne muscular dystrophy.

The experiments reported herein compare growth kinetics and biochemical properties of cultured skin fibroblasts from patients with Duchenne muscular dystrophy (DMD) and matched normal controls. On day 7 after plating (6000 cells/cm2) cell number and DNA per dish are significantly reduced (P less than 0.0001) in the cultures from DMD patients (n = 14), compared to those from controls (n = 10). Moreover DMD cells contain less lipids and proteins per dish but more per cell than normal fibroblasts (not significant). Variations of media (McCoy's medium instead of Eagle's minimum essential medium) resulted in the same differences between DMD and control cells. Cell kinetic experiments (plating density: 2000 cells/cm2) show increased doubling times of DMD fibroblasts (P less than 0.001; nDMD = 5; ncontrols = 4) whereas plating efficiency is equal for both DMD and controls. On day 7 activity of the membrane bound enzyme 5'-nucleotidase either per mg protein or per microgram DNA is significantly elevated in cells from DMD patients (P less than 0.0005; nDMD = 8; ncontrols = 9) independent of cell density. Thus all findings in cultured DMD fibroblasts: increased doubling time, tendency to more voluminous cells, and elevated 5'-nucleotidase activity per cell suggest, that the DMD cells behave similar to prematurely aging cells. Until now we were not able to check whether any alterations of the plasma membrane are inducing early senescence or, reversely, premature aging is the cause of the postulated membrane alterations. If these findings were to be confirmed in cultured amniotic cells from DMD fetuses, thay could serve as a potential prenatal diagnosis of the disease.

Adolescent↗

[Twin pregnancy with operative removaL of one fetus with chromosomal mosaicism 46,XX/45,XO and term delivery of a healthy baby].

During antenatal amniocentesis in a case of twin pregnancy, a healthy child 46,XY and a Turner-mosaic 46,XX/45, XO are diagnosed. The parents wish for an abortion, with an attempt to save the healthy child. the affected child is removed by sectio parva in the 22nd week of pregnancy, and the other child is delivered by caesarean section in the 39th week. Our experiences with regard to the management of dizygotic twins where antenatal morbidity of one of the fetuses occurs are compared and discussed with two similar cases from the literature.

Abortion, Induced↗

Distribution of cytoskeletal elements in cultured skin fibroblasts of patients with Duchenne's muscular dystrophy.

Cultured fibroblasts from patients suffering from Duchenne's Muscular Dystrophy were examined by indirect immunofluorescent techniques using antibodies against actin, myosin, tubulin, and intermediate-sized filaments. The cells display normal patterns of microfilamentous bundles (stress fibres), microtubules, and intermediate-sized filaments suggesting a normal organization of these cytoskeletal structures.

Actins↗

Intra- and extravascular volume changes in the human forearm after static hand grip exercise.

Studies have been conducted to evaluate intra- and extravascular volume changes and blood flow in the exercising human forearm by means of (1) combining plethysmographic and scintigraphic methods, (2) an indirect procedure using the relationship of blood flow and volume change from reactive hyperemia. A static hand grip exercise of 60% maximal voluntary contraction and 30 s duration increased the forearm volume by 3.03 +/- 0.65 ml/100 ml soft tissue, involving both the intra- and extravascular volume components. There is a quantitative and qualitative difference in the time course of change in these components, showing an extravascular part of about 50% for the 2-min post-exercise value and a substantially slower rate of recovery. Experiments involving muscle work at intervals (50% maximal voluntary contraction, 30 s duration, 2-min intervals) caused a further increase in extravascular volume. Furthermore, the study suggests that the flow-volume relationship from reactive hyperemia may be considered to be available for the determination of local blood volume changes in exercise hyperemia. The results are discussed in connection with the influence of anaerobic muscle metabolism and conclusions referring to this are drawn about the use of plethysmographic methods.

Adult↗