Dandy-Walker variant in Coffin-Siris syndrome

We describe a five-month-old male infant with Coffin-Siris syndrome, the so-called Dandy-Walker variant (hypoplasia of the cerebellar vermis with cystic dilatation of the fourth ventricle, but without enlargement of the posterior fossa), and partial agenesis of the corpus callosum. Dandy-Walker malformation and mega cisterna magna, but not Dandy-Walker variant, have been reported in Coffin-Siris syndrome. The presence of Dandy-Walker variant in the infant we described confirms that the full continuum of the Dandy-Walker complex can occur in Coffin-Siris syndrome. The yet unidentified gene(s) for the syndrome may be related to the development of the hindbrain.     

Densitometric determination of human papillomavirus DNA quantities by chromato-scanning in the fluorescence mode.

The quantitation of human papillomavirus DNA isolated from warts by chromato-scanning (fluorescence mode) photographs of ethidium bromide-stained agarose gels is described. Excitation at 200 nm (with a cutoff filter at 400 nm) generates fluorescence from the white portion of the printing paper. The fluorescent intensity correlated with the quantities of DNA in the band of interest. The amounts of DNA were determined using calibration curves of approximately the same size as lambda phage DNA fragments. This general method of quantification is applicable to photographs of other types of polynucleotides capable of being separated and stained in a gel medium.     

Suppressor activity in the supernatant of T cell clones derived from chimeric mouse spleen cells

The supernatant from cultures of T cell clones derived from (BALB/c----C3H/He) chimeras suppresses BALB/c anti-C3H/He or BALB/c anti-C57BL/6 MLRs. When we studied the alloantigen specificity of the suppressor activity in culture supernatant, we observed three types of the suppressor activity (i.e., the suppressor activity against BALB/c anti-C3H/He MLR, against BALB/c anti-C57BL/6 MLR, and against both MLRs) on day 3 after stimulation of the T cell clones with 20% crude IL2 and feeder cells. Since the alloantigen specificity fluctuated somewhat with time, we considered that a time-course study was needed to determine it correctly. We thought it unlikely that any IFN-gamma or PGE2 in the culture supernatant of the T cell clones would have mediated the suppression. Our results suggest that alloantigen specific and non-specific suppressor T cells exist in bone marrow chimeras. The former appears to play an important role in inducing and maintaining transplantation tolerance, while the latter seems to have a rather harmful effect upon chimeras.     

The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals

Free radicals are involved in the pathogenesis and/or progression of Parkinson's disease (PD). Several ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and to show a neuroprotective effect in vivo. We investigated the in vitro free radical scavenging and antioxidant activities of cabergoline, a long-acting ergot DA agonist, as well as its ability to activate glutathione (GSH), catalase (Cat) and superoxide dismutase (SOD) activating effects and its in vivo neuroprotective properties against 6-hydroxydopamine (6-OHDA) intracerebroventricularly (i.c.v.) in mice. The striatal DA turnover induced by i.c.v. injection of 6-OHDA was completely normalized by pretreatment with cabergoline. Moreover, cabergoline scavenged free radicals in vitro and significantly reduced lipid peroxidation in vitro and in vivo. Furthermore, daily administration of cabergoline to mice significantly increased striatal GSH levels by activation of RNA expressions of GSH-related enzymes, although striatal Cat and SOD activities did not change. In addition, our present results suggest that repeated administration of cabergoline attenuates both 6-OHDA-induced nigrostriatal DAergic dysfunction and DA neuronal cell death, since cabergoline also had a neuroprotective effect in the immunohistochemical experiment. In conclusion, our findings indicate that the multiple antioxidant mechanisms of cabergoline, such as activation of the GSH system and the direct free radical scavenging activity, may explain the neuroprotective effect of this ergot DA agonist.     

Three-dimensional ultrasonography in the first trimester of human pregnancy

Our purpose was to visualize normal embryonal and fetal surface anatomical structures in the first trimester of human pregnancy by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. Four embryos and 31 fetuses of 8-13 weeks gestation were studied with a specially-developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and can also generate, within seconds, high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. The percentage of surface anatomical structures visualized at each gestational age interval using two-dimensional and three-dimensional ultrasonography is presented. Head and trunk were depicted in all cases. The number and the clarity of visualization of face, upper and lower extremities, hand, and foot increased with advancing gestation. The free loop of the umbilical cord was depicted in most cases. The number of depictions of abdominal cord insertion, midgut herniation, and yolk sac decreased with the increase of gestation. Genitals could not be identified in the first trimester. The ability to view some surface anatomical structures (face, hand, and foot) was better with three-dimensional ultrasonography than with two-dimensional ultrasonography. Three-dimensional ultrasonography provides a novel means for visualization of surface anatomical structures of the embryo and early fetus. These results suggest that three-dimensional ultrasonography can become an important modality in future embryological and early fetal research and in detection of embryonic and fetal developmental disorders in the first trimester of pregnancy.      

Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor receptor-associated periodic syndrome and with systemic lupus erythematosus in Japanese

Molecular defects of TNFRSF1A was investigated in members of a family presenting with typical phenotypes of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and in patients with the autoimmune disorders, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Genomic DNA from the members of a family with typical TRAPS, as well as from 100 patients with SLE, 100 patients with RA and 100 healthy individuals, was studied for mutations in exons 2, 3 and 4 of the TNFRSF1A gene. All individuals were Japanese. Three novel missense mutations were identified in the TNFRSF1A. The C70G mutation was identified in family members with typical TRAPS, which was the second case in eastern Asian population. In addition, the T61I and R104Q mutations were each identified in 2 of the 100 SLE patients. The T61I mutation was identified in one of the 100 healthy individuals. No mutations were identified in the 100 RA patients. Functional analysis revealed that PMA-induced shedding of TNFRSF1A from PBMCs was impaired in a patient carrying T61I. A larger scale of study will clarify whether these two mutations, T61I and R104Q, are associated with chronic inflammatory disorders, such as SLE, or not.     

Characterization of T-cell tolerance to hepatitis B virus (HBV) antigen in transgenic mice.

We made three different lines of hepatitis B virus (HBV) transgenic mice which express different amounts of hepatitis B e antigen (HBeAg) and/or hepatitis B core antigen (HBcAg) to analyse the cellular mechanisms of HBcAg specific T-cell tolerance. BS10 (official designation, 1.2HB-BS10) transgenic mice, which contain the whole HBV genome, express relatively high amounts of HBeAg in the serum and HBcAg in the liver. SPC mice, which contain hepatitis B virus core and precore gene, express small amounts of HBeAg in the serum but not HBcAg in the liver. SC33 mice, which contain only hepatitis B core gene, do not express HBeAg in the serum but express HBcAg in the liver. BS10 mice showed a very low anti-HBc antibody response after primary and secondary immunizations with recombinant HBcAg compared to transgenic host C57BL/6 (B6) mice. SPC mice showed an almost equal level of anti-HBc antibody response compared to B6 mice. SC33 mice contained anti-HBc antibody even before immunization and showed high titres of anti-HBc antibody response after immunization with HBcAg. Analysis of cellular site(s) of low responsiveness of BS10 mice revealed that proliferating and helper T cells are specifically tolerant to HBcAg. B cells and antigen-presenting cells in BS10 mice were not defective. SC33, SPC and BS10 mice differ a little in their developmental expression of HBc/HBeAg. Our results suggest critical roles of the nature (circulating versus non-circulating) as well as the time of expression of self-antigens in T-cell tolerance.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.