Makoto Ninomiya

EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) with a balanced reciprocal translocation between 7q11.21 and 9p12 (or 7p11.2 and 9q12) in three generations

Familial cases (a grandfather, a father and a daughter) of the EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) are reported. All of them have a balanced reciprocal translocation (46,XY or XX, t(7;9) (q11.21;p12) or (46,XY or XX, t(7;9) (p11.2;q12)), but no other members of the family have either the EEC syndrome or chromosome abnormalities. This indicates that one of the chromosome sites 7q11.21, 9p12, 7p11.2 and 9q12 is a candidate for gene locus of the EEC syndrome.

The Production of Cardiovascular Malformations with Combined Use of Antisera to Kidney and Fetal Heart

ABSTRACT: Wistar rats were administered rabbit anti‐fetal‐rat‐heart serum (AFHS) alone on day 9 of gestation or in combination with sub‐teratogenic doses of rabbit anti‐rat‐kidney serum (AKS).

Epidemiologic Survey of Children with End‐Stage Renal Disease

We performed an epidemiologic study on the basis of a questionnaire survey of 162 children with end‐stage renal disease (ESRD). Sixty‐nine (43%) of our 162 children, including 25 detected at mass screening of urine, were found by chance hematuria and/or proteinuria. The three major causes of ESRD in our children were chronic glomerulonephritis (CGN) in 56, congenital anomalies of the urinary tract in 30, and nephrotic syndrome (NS) in 27. The renal pathology in 39 children with CGN or NS was focal glomerular sclerosis in 15, diffuse mesangial GN in 7, IgA GN in 5, membranoproliferative GN in 3, membranous GN in 3, and unclassified in 6. Forms of dialysis initiated were hemodialysis in 91 children, continuous ambulatory peritoneal dialysis (PD) in 66, and intermittent PD in 5. Renal transplantation was performed on 38 children, and the graft and the patient survival rates were 76% and 89%, respectively. The survival rate of our 162 children for a mean follow‐up of 8.1 years was 77%. In conclusion, an integrated program of maintenance dialysis and transplantation provides a favorable life for children with ESRD.

The Production of Cardiovascular Malformations by Use of Antikidney and Antiheart Sera

Cardiovascular malformations were produced in 46.7% of Wistar rats by injecting a sub‐ teratogenic dose of rabbit anti‐rat‐kidney serum and 0.90ml per 100g of rabbit anti‐rat‐heart serum. Ventricular septal defects and aortic arch anomalies were the most common cardiovascular malformations observed. Antikidney serum was found to be very teratogenic, but the 0.10ml per 100g dosage was considered to be sub‐teratogenic. The results suggest that antiheart serum alone is not teratogenic, but when combined with a sub‐teratogenic dose of antikidney serum the combination proved to be teratogenic and resulted in an increase in cardiovascular malformations when compared to the effect of antikidney serum alone.

The Production of Cardiovascular Malformations with Combined Use of Trypan Blue and Anti-Heart Serum in the Rat

Small doses of trypan blue (TB) and anti‐heart serum (AHS) were intraperi‐toneally injected into pregnant Wistar rats to produce in the offspring cardiovascular malformations, which in our previous studies had been induced by the combined use of anti‐sera to two tissues. The results showed that TB could produce a high incidence of malformations, though a dose of 10 mg/kg was subteratogenic in rats. AHS alone was not teratogenic even if 9 ml/kg were administered. Combined use of 10 mg/kg of TB (on day 9 of gestation) and 9 ml/kg of AHS (on day 10) produced a statistically significant increase of malformations (p<0.001). The total incidence of malformations and the incidence of those of the cardiovascular system were 91.5% and 83.1%, respectively. Ventricular septal defects and aortic arch anomalies were the main cardiovascular malformations. Localization of TB in both the yolk sac and the developing embryo was comfirmed, though deposition of AHS was not detected. In this study, the incidence of cardiovascular malformations was higher than that achieved in our previous study, which utilized a combination of small doses of anti‐kidney serum and AHS.

Effects of presensitization of antiheart serum on the rat embryonic heart

SummaryAfter sensitization by rabbit anti-rat-heart serum (AHS), Wistar rats were injected with 9 ml/kg of AHS on day 9 of gestation. The incidence of malformations was 31.5% and that of cardiovascular malformations was 21.8%. The main malformations were microphthalmia, ventricular septal defect, pulmonary stenosis, and general edema. No antinuclear antibody was detected in the maternal sera by the fluorescent antibody technique. No complete heart block was found in the fetuses by electrocardiography. The fluorescent antibody technique demonstrated localization of rat IgG and rat C3 on the maternal myocardium, but a light-microscopic study revealed no myocarditis or endocarditis in either the maternal or the fetal heart. The types of malformation were similar to those observed after a single administration of antikidney serum, which presumably involves yolk sac dysfunction. These results show that both the existence of the immune complexes of antibodies against AHS and the administration of AHS on day 9 are necessary to cause yolk sac dysfunction or other teratogenic changes.

Cardiovascular Anomalies Induced by Anti‐Tissue Sera and Immunological Cross‐Reaction

Wistar rats were administered rabbit anti‐tissue serum alone or in combination with sub‐teratogenic doses of anti‐kidney serum (AKS) on day 9 of gestation. The results showed that the incidence of cardiovascular malformations was highest (46.7%) when a small dose (1 ml/kg) of AKS given on day 9 was followed by 9 ml/kg of anti‐heart serum (AHS) on day 10. The most common cardiovascular malformations were ventricular septal defects associated with aortic arch anomalies. The spectrum of malformations did not vary with the injected sera. Immunodiffusion studies indicated that the kidney, umbilical cord and yolk sac tissues have at least one common antigen. Between the AHS and the kidney antigen, a slight precipitin band was also demonstrated. These results suggest that the synergistic effects of antisera depend on the degree of immunological cross‐reaction with the yolk sac, and that the mechanisms of teratogenicity by the combined administration is caused mainly by yolk sac dysfunction.

The Effects of M-protein Fraction of Hemolytic Streptococci on Embryonic Development in the Rat

ABSTRACT  Wistar rats were administered M‐protein fraction (MP) of group A type 12 hemolytic streptococci or rabbit anti‐MP serum (AMPS) on day 9 of gestation. The incidence of malformations was 11.8% when 9 mg/kg of MP was administered and 12.0% when 9 ml/kg of AMPS was injected. The main malformations observed in both groups were ventricular septal defect, microphthalmia, anophthalmia, and hydrocephaly. Light and electron microscopic studies revealed no myocarditis nor endocarditis in either the maternal or fetal heart. Fluorescent antibody technique demonstrated no localization of anti‐MP antibodies on the maternal heart. The results suggest that MP and AMPS are slightly teratogenic in the rat, and that the teratogenesis is not caused by an autoimmune mechanism.

The production of cardiovascular malformations using fetal rat heart antiserum

Pregnant Wistar rats received antiserum to fetal rat heart on the ninth day of gestation (plug day = 0 day) in doses ranging from 0.3 to 0.9 ml per 100 g. The incidence of cardiovascular malformation produced by this antiserum (0.90 ml/100 g) was 5.2 per cent. But, the same antiserum, when injected into pregnant rats on day 10 in dose of 0.9 ml per 100 g after the injection of subteratogenic dose (0.10 m1/100 g) of antikidney serum, resulted in a significant increase in the incidence (46.3%) of cardiovascular malformation (see the Table). The malformation mainly observed included ventricular septa1 defect, aortic arch anomalies, and double outlet right ventricle. These results were similar to those obtained in our previous study using adult rat heart antiserum. The results suggest that the fetal rat heart antiserum alone should not be teratogenic, but when given with subteratogenic dose of anti-kidney serum it will become teratogenic, and there will be an organ-specific activity to the fetal rat heart antiserum, similarly the adult rat heart antiserum.