A cytogenetic study of nonpolymalformed patients with mental retardation of clinically undefined etiology: application of a high resolution banding technique.

We performed a cytogenetic study on 140 nonpolymalformed patients with mental retardation of clinically undefined origin, using a high resolution banding technique, to determine how much chromosome abnormalities contribute to the etiology of this condition. A total of 15 patients (10.7%) were found to have autosomal or sex chromosomal abnormalities. Autosomal abnormalities included partial monosomy (5 cases), reciprocal translocation (one case), 13/14 robertsonian translocation (3 cases), unbalanced translocation (one case), inverted duplication of 15q (one case) and mosaic trisomy 21 (one case). Sex chromosomal abnormalities comprised structural rearrangement of the short arm of the X chromosome (one case) and 47, XXY in a pure or mosaic form (two cases). It should be noted that four out of the 5 cases of partial monosomy had subtle interstitial deletions, which might have been unidentified by the conventional G-banding method alone. In one case of the robertsonian translocation 46,XY,t(13;14)/45,XY,t(13;14), a small deletion was thought to have occurred in the cells with a chromosome number of 45. Comparison of clinical features of the 15 chromosomally abnormal patients with those of patients with normal karyotypes did not show any clinical parameter indicative of chromosome imbalance. These results suggest that a subtle chromosomal deletion is specific to mental retardation associated with few malformations. We believe that diagnostic evaluation of mentally retarded patients, even if nonmalformed, should include chromosome analysis using a high resolution banding technique.</p

Turbid intrusion below the thermal staircase in the seasonal thermocline of Lake Biwa

Thermal 'staircase', a layer of constant temperature between the sheets of the steep gradients, was formed in the seasonal thermocline, which was 2.5 m above the bottom at a point of 18 m deep on the boundary slope in Lake Biwa. Following a sediment resuspension event when a moderate onshore wind blew, bed materials should be suspended up to the thermocline, then settled down forming a staircase above the turbid intrusion. Comparing the observed downward hear flux with the settling flux of sediment, it was found that double-diffusive convection would play an important role on the formation of the whole structure consisting of the staircase and turbid intrusion along with chemical anomalies and dense population of phytoplankters, which were fed by nutrients supplied from the bottom sediment under a typical condition of drought. Laboratory experiments were conducted to demonstrate the thermal and sediment processes in the stratified lake. Resuspension process due to surface and internal waves was examined using a tank with a sloping bottom, while the settling process was investigated by using a deep, diffusive tank. Formative process and scales of the staircase and intrusion were discussed relating with the intensity of resuspension and the buoyancy fluxes

SF-10 induces cell-mediated immunity

We reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific IgA in nasal and lung washes and IgG in sera with their neutralizing activities. Since CD8+ T cell-mediated protection is an important requirement for adaptive immunity, we investigated in this study the effects of SF-10 with antigen on local and systemic cell-mediated immunity. Nasal instillation of ovalbumin, a model antigen, combined with SF-10 efficiently delivered antigen to mucosal dendritic and epithelial cells and promoted cross-presentation in antigen presenting cells, yielding a high percentage of ovalbumin-specific cytotoxic T lymphocytes in the nasal mucosa, compared with ovalbumin alone. Nasal immunization of HAv-SF-10 also induced HAv-specific cytotoxic T lymphocytes and upregulated granzyme B expression in splenic CD8+ T cells with their high cytotoxicity against target cells pulsed with HA peptide. Furthermore, nasal vaccination of HAv-SF-10 significantly induced higher cytotoxic T lymphocytes-mediated cytotoxicity in the lungs and cervical lymph nodes in the early phase of influenza virus infection compared with HAv alone. Protective immunity induced by HAv-SF-10 against lethal influenza virus infection was partially and predominantly suppressed after depletion of CD8+ and CD4+ T cells (induced by intraperitoneal injection of the corresponding antibodies), respectively, suggesting that CD4+ T cells predominantly and CD8+ T cells partially contribute to the protective immunity in the advanced stage of influenza virus infection. These results suggest that SF-10 promotes effective antigen delivery to antigen presenting cells, activates CD8+ T cells via cross-presentation, and induces cell-mediated immune responses against antigen

Oral vaccination with influenza hemagglutinin combined with human pulmonary surfactant-mimicking synthetic adjuvant SF-10 induces efficient local and systemic immunity compared with nasal and subcutaneous vaccination and provides protective immunity in mice

We reported previously that a synthetic mucosal adjuvant SF-10, which mimics human pulmonary surfactant, delivers antigen to mucosal dendritic cells in the nasal cavity and promotes induction of humoral and cellular immunity. The aim of the present study was to determine the effects of oral administration of antigen combined with SF-10 (antigen-SF-10) on systemic and local immunity. Oral administration of ovalbumin, a model antigen, combined with SF-10 enhanced ovalbumin uptake into intestinal antigen presenting MHC II+CD11c+ cells and their CD11b+CD103+ and CD11b+CD103- subtype dendritic cells, which are the major antigen presenting subsets of the intestinal tract, more efficiently compared to without SF-10. Oral vaccination with influenza hemagglutinin vaccine (HAv)-SF-10 induced HAv-specific IgA and IgG in the serum, and HAv-specific secretory IgA and IgG in bronchoalveolar lavage fluid, nasal washes, gastric extracts and fecal material; their levels were significantly higher than those induced by subcutaneous HAv or intranasal HAv and HAv-SF-10 vaccinations. Enzyme-linked immunospot assay showed high numbers of HAv-specific IgA and IgG antibody secreting cells in the gastrointestinal and respiratory mucosal lymphoid tissues after oral vaccination with HAv-SF-10, but no or very low induction following oral vaccination with HAv alone. Oral vaccination with HAv-SF-10 provided protective immunity against severe influenza A virus infection, which was significantly higher than that induced by HAv combined with cholera toxin. Oral vaccination with HAv-SF-10 was associated with unique cytokine production patterns in the spleen after HAv stimulation; including marked induction of HAv-responsive Th17 cytokines (e.g., IL-17A and IL-22), high induction of Th1 cytokines (e.g., IL-2 and IFN-γ) and moderate induction of Th2 cytokines (e.g., IL-4 and IL-5). These results indicate that oral vaccination with HAv-SF-10 induces more efficient systemic and local immunity than nasal or subcutaneous vaccination with characteristically high levels of secretory HAv-specific IgA in various mucosal organs and protective immunity

Induction of systemic and mucosal immunity and maintenance of its memory against influenza A virus by nasal vaccination using a new mucosal adjuvant SF-10 derived from pulmonary surfactant in young cynomolgus monkeys

Induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant SF-10 derived from pulmonary surfactant constituents. Split-product of influenza virus A/California/7/2009(H1N1)pdm hemagglutinin vaccine (HAv) at 15 μg with or without SF-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. SF-10-adjuvanted HAv (SF-10-HAv) elicited significantly higher HAv-specific IgG and hemagglutinin inhibition (HI) titers in serum and HAv-specific secretory IgA and its neutralizing activities in nasal washes compared with HAv antigen and SF-10 alone. Significant cross-neutralizing activities of nasal washes after the third vaccination to several other H1N1 and H3N2 strains were observed. HI titers in serum and neutralizing activities in nasal washes reached peak levels at 6 weeks after initial vaccination, then gradually decreased after 10 weeks and returned to the baseline levels at 36 weeks. A single intranasal revaccination of SF-10-HAv at 36 weeks rapidly and significantly increased both immunity in serum and nasal washes compared with naïve monkeys. Revaccination by one or two doses achieved almost maximal immunity at 2 or 4 weeks after instillation. Statistically significant adverse effects (e.g., body weight loss, elevated body temperature, nasal discharge, change in peripheral blood leukocyte and platelet counts) were not observed for 2 weeks after vaccination of SF-10-HAv, HAv or SF-10 and also during the experimental period. These results in young monkey model suggest the potential of clinical use SF-10 for intranasal flu vaccine

Multivariate analysis of dermatoglyphics of severe mental retardates: an application of the constellation graphical method for discriminant analysis.

We studied the dermatoglyphics of 353 severe mental retardates (excluding those with chromosomal abnormalities and major limb malformations), using multivariate analysis, to determine how early intrauterine factors are related to the etiology of mental retardation. First, dermatoglyphics were compared between 140 individuals with undefined prenatal factors and 700 normal controls. After 6 and 9 dermatoglyphic traits were chosen as discriminative variables for males and females, respectively, the data were subjected separately for each sex to the constellation graphical method for discriminant analysis. The same formula as obtained in the idiopathic group was subsequently applied to data from cases in other etiological categories. When the misclassification rate was 0.03, the rates of correct classification of the male patients into the etiological categories of undefined prenatal, defined prenatal, perinatal, postnatal and unknown (no anamnestic data available) categories were 19.7% (13/66), 20.0% (3/15), 8.8% (5/57), 5.0% (1/20) and 7.7% (2/26), while the correct classification rates of females were 24.3% (18/74), 42.1% (8/19), 18.9% (7/37), 5.1% (1/16) and 13.0% (3/23), respectively. The results suggest that early intrauterine factors such as those producing dermatoglyphic deviations may contribute to the pathogenesis of severe mental retardation not only in patients with undefined prenatal etiological factors but also in those with perinatal factors, especially those of the female sex.</p

Farber's disease (disseminated lipogranulomatosis): the first case reported in Japan.

We report the first case in Japan, i.e., the first case among oriental subject of Farber's disease. This is a rare disorder of lipid metabolism in infancy subsequent to a genetically-determined defect in ceramide degradation. Main features are characterized clinically by hoarseness, joint swelling, subcutaneous nodules and retarded psychomotor development. Lipid analysis and pathological investigation on the material obtained from a subcutaneous nodule confirmed clearly the presence of ceramide and intracytoplasmic inclusion bodies characteristic for Farber's disease. In this case, we experienced also corneal opacity and striking abnormalities in electroencephalogram, which have apparently not been noticed in the 17 cases hitherto reported.</p

Detection of hepatitis B surface antigen subtype adr in an epidemic of papular acrodermatitis of childhood (Gianotti's disease).

Papular acrodermatitis of childhood (PAC) has recently been reported to be associated with hepatitis B surface antigen (HBsAg) subtype ayw. Between September, 1978, and June, 1979, we saw 14 patients with PAC in a small epidemic occurring in Iwakuni City, Japan. HBsAg was detected in sera from all patients. Subtyping of HBsAg in 11 patients showed that 8 had a determinant adr and 3 had no detectable determinant because of low antigen titers. The result suggests that factors other than the specific HBsAg subtype contribute to the development of PAC.</p