Makoto Higurashi

In vitro chromosomal radiosensitivity in “chromosomal breakage syndromes”

Peripheral blood samples from 11 children with “the chromosomal breakage syndromes,” ataxia‐telangiectasia, Blooms syndrome, and Fanconis anemia, and from 4 normal children were irradiated with 10 and 100 rads. Non‐irradiated duplicate cultures were used to determine the pre‐irradiation breakage. All cultures were harvested at 52 hours. Radiation‐break frequencies were calculated by subtracting figures for non‐irradiated samples from those for irradiated samples. The number of chromosome‐type breaks per cell per rad was: 0.0017 ± 0.0012 in controls, in ataxia‐telagiectasia 0.0062 ± 0.0019, in Blooms syndrome 0.0061 ± 0.0019, and in Fanconis anemia 0.0085 ± 0.0023. The number of dicentrics and rings per cell after 100 rads was significantly greater in samples from chromosomal breakage syndromes than in controls. We concluded that, in vitro, chromosomes of cells from children with chromosomal breakage syndromes were significantly more radiosensitive than those of controls.

In-vitro chromosomal radiosensitivity in Fanconi's anemia

Peripheral blood samples and fibroblast cultures from 5 children with Fanconis anemia and 5 contorl were irradiated with 10 and 100 rads; other controls were non-irradiated with 10 and 100 rads; other controls were non-irradiated duplicate cultures. Blood cultures were harvested at 52 and 72 hours. Fibroblast cultures were irradiated 24 hours before fixation. Radiation break frequencies were calcultaed by subtracting figures for non-irradiated samples from those fro irradiated samples. The number of chromosome-type breaks per cell per rad in irradiated controls was 0.0025 ± 0.0005 (52 hour cultures) and 0.0017 ± 0.005 (72 hours cultures) in lymphocytes, and 0.0059 ± 0.0016 in fibroblasts, and in irradiated cells from Fanconis anemia was 0.0103 ± 0.0016 (52 hour cultures) and 0.0074 ± 0.0036 (72 hour cultures) in lymphocytes, and 0.0103 ± 0.0034 in fibroblasts. The number of dicentrics and rings per cell was significantly greater in the Fanconis anemia samples than controls at 100 rads. We concluded that, in-vitro, chromosomes of cells from children with Fanconis anemia were significantly more radiosensitive than those of controls (P < 0.01).

Incidence of major chromosome aberrations in 12,319 newborn infants in Tokyo

SummaryIn order to ascertain the frequency of chromosome aberrations among newborn infants in Japan, a chromosome survey of a large number of newborn infants is in progress. A consecutive series of 12,319 newborn babies, 6382 male and 5937 female, have been screened for clinical manifestations of autosomal aberrations and for sex chromatin and sex chromosome aberrations. Chromosome studies were carried out on 694 infants with suspected chromosome aberrations. The clinically abnormal infants were screened by conventional staining, and banding techniques have been used in the part of the study performed since 1974. Of the clincally abnormal infants, 25 had abnormal karyotypes, including two males with a 47,XXY complement, one female with a 45,X complement, three male infants with a 47,XYY complement, two with trisomy 13 syndrome, three with trisomy 18 (including one case of mosaicism), eleven with Downs syndrome (including one case of mosaicism), one with B5p partial trisomy, one with cri-du-chat syndrome, and one with Y/D translocation. The overall results are comparable to those of previous population cytogenetic studies only in the autosomal trisomies and sex chromosome abnormalities and in that the observed frequencies were comparable to those found in studies in Caucasians.

In vitro chromosomal radiosensitivity in patients and in carriers with abnormal non-Down's syndrome karyotypes.

Extract: This paper reports in vitro tests of chromosomal radiosensitivity in five children and three adults with normal karyotypes as control subjects, in seven patients (children) with chromosomal abnormalities, and in six translocation carriers (adults). Peripheral blood samples from each individual and skin fibroblast cultures from four children in the control group, five patients with chromosomal abnormalities, and one translocation carrier were irradiated with 10 and 100 rads. Nonirradiated duplicate cultures were used as controls. Blood cultures were harvested after 52 hr of incubation and fibroblast cultures were harvested 24 hr after irradiation. The frequency of chromosomal breakage caused by irradiation was calculated by subtracting the values for nonirradiated samples from those for irradiated samples. In normal control subjects, the number of chromosome-type breaks per cell per rad was 0.0024 ± 0.0009 and 0.0020 ± 0.0009 in lymphocytes of children and adults, respectively, and 0.0049 ± 0.0021 in fibroblasts of children. The number of breaks per cell per rad was 0.0055 ± 0.0017 in lymphocytes and 0.00:82 ± 0.0013 in fibroblasts of patients, and 0.0040 ± 0.0018 in lymphocytes and 0.0063 ± 0.0017 in fibroblasts of carriers. In comparison with age-matched controls, significantly elevated frequencies of breaks per cell per rad were observed in cultured lymphocytes and fibroblasts of patients, and in cultured lymphocytes of translocation carriers (Table II). After irradiation with 100 rads, the number of dicentrics and rings per cell was significantly greater in both patients and carriers of chromosomal abnormalities than in control subjects (Tables I and III). Therefore, chromosomes of cells of patients with chromosomal abnormalities and of translocation carriers were significantly more radiosensitive in vitro than those of control subjects.Speculation: Patients with chromosomal abnormalities and carriers with a translocated chromosome show greater chromosomal changes after irradiation in all age groups than do normal control subjects. These individuals, therefore, should be subjected to as little x-ray examination as possible.

Retrocaval Ureter with Recurrent Pyelonephritis

A case of retrocaval ureter with recurrent pyelonephritis is presented with discussion of these clinical entities. An excretory urogram and retrograde ureterogram disclosed pronounced hydronephrosis as well as a dilated proximal part and reversed J-shaped appearance of the right ureter. The compressed retrocaval portion of the ureter was resected and an end-to-end anastomosis was performed anterior to the vena cava. Due to the progressive kidney damage leading to severe hydronephrosis, a rapid radiological diagnosis should be made to replace the retropositioned ureter.

The transition in frequency of Y chromatin in males during the neonatal period.

SummaryThe frequency of Y chromatin, visualized as fluorescent bodies in cell nuclei from lymphocytes in blood smears, was signficantly less in newborn males than in three-month-old male infants and adults. The frequency of Y chromatin-positive cells on day 0 was 36.16±9.11% and then increased daily. At one month after birth the frequency was 55.07±9.29%, which was not significantly different from that in adult males (57.08±5.97%).

A Seroimmunological Analysis of Down Syndrome

Down syndrome (DS) was studied in terms of immunological function and serological aspects. It was found that antibody levels against rubella and pertussis in the sera from 36 institutionalized DS patients were comparable with those of healthy controls while low antibody levels were detected against mumps and measles. Six tumor markers were also assayed in the serum from DS patients and the serum concentration of alpha-1-acid glycoprotein (alpha 1-AGP) and immunosuppressive acidic protein, an analogous glycoprotein of alpha 1-AGP, were significantly higher than those of the control group. Multivariate discriminant function was constructed based on the concentration of tumor markers. The function could discriminate between the two groups at a sensitivity of 92.3%. Flow-cytometrical analysis has revealed that helper T level of DS patients sera was lower than that of the control group.

Quinacrine and acridine-R banding without a fluorescence microscope.

SummaryA technique is described in which a standard fluorescence microscope equipped with a high-pressure mercury lamp is replaced with an ordinary laboratory microscope fitted with a quartz-iodine lamp. A dark field condenser and a set of three filters, including an FITC interference filter, complete a ‘fluorescence’ microscope.The microscope has proved itself satisfactory in the study of Y-chromatin, chromosome Q-bands including Q-polymorphism, and acridine-R band. It is very easy to operate and does not emit ultraviolet light, which might harm operators. Total cost of the quartz-iodine lamps outfit, filters, and a dark-field condenser is much less than that of a standard fluorescence microscope. The cost is especially low when a laboratory microscope with a quartz-iodine lamp is already at hand. Spectrofluorometric studies of QM and Q indicate that the present system will show even better performance if an interference filter with a transmission range of about 400 to 440–450 nm is designed and used in combination with a 455–475 nm barrier filter.

Ethics and fetal medicine

SummaryEthical issues in the clinical practice of fetal medicine are discussed, largely from the point of view of early prenatal medicine. The discussion concentrates on several aspects including the time when human life begins, the pros and cons of fetal medicine, and ethical guidelines for fetal medicine. The emphasis is placed on the importance of informed consent and an increase in genetical knowledge amongst the general public.