Biomedical subjects
Publications and source records attributed to J Kleinebrecht.
81 embryos from spontaneous abortions were analyzed histologically. In 35 of these cytogenetic analysis was successful and showed 16 embryos with chromosomal aberrations. These cases are described in detail.
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Pregnant mice (C57B1/6JFfm) were treated with BUdR on day 9 of gestation. For doses ranging from 300 to 1,200 mg/kg b.w. of BUdR the teratogenic effect in near-term fetuses was analyzed. The findings confirm the phase and dose dependency of the induced malformations found by other authors. They also demonstrate, however, a BUdR-specific induction of special malformations. For a dose of 1,200 mg/kg of BUdR the effect on mitotic rates and the induction of chromosomal aberrations were investigated. Mitotic rates were counted in single organs as well as in total homogenized embryos. The methods are equally useful. The embryos were analyzed 3, 6, 12, and 24 hours after BUdR treatment either after homogenization or in serial sections. Decrease of mitotic rates has been found to be most remarkable at 3 and 12 hours after treatment. At 24 hours only the neural tissue showed a slight decrease of the mitotic rate. Chromosomal aberrations are induced at all times, but the highest rates are seen at 3 and 12 hours after treatment. The aberrations are of the chromatid type.
Homozygotes of the mouse mutant limb-deformity (ld) reveal a reduced fertility and a high mortality of newborns. Unilateral and bilateral aplasia of kidneys is very common. In unilateral aplasia the right side is affected most, with no sex preference. All extremities show aplasias and synostoses, with 22 malformation types in the forelimbs and 8 types in the hindlimbs. Primary and secondary fusions of limb elements are found.
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Treating mice of strain C57BL/6Ffm on day 9 of gestation with 10 mg/kg of 5-fluoro-2'-deoxycytidine (FCdR) resulted in malformations of the thoracic vertebral column (ThVC) in 98% of near-term fetuses (Degenhardt et al., 1968). The spectrum of malformations was broad: fusion, dysplasia, cleft, aplasia and hypoplasia were all produced. Fusions of two or more segments represented more than half of all malformations (Bosse, 1978). The alterations in embryonic precartilage and cartilage after FCdR-treatment were followed from day 11 to day 15 in a biochemical and histological study. Biochemically, the 35S-uptake into embryonic mucopolysaccharides (MPS) and the content of total MPS and seven fractions of MPS in embryos or isolated ThVCs were analyzed. The histological variables studied were the types and incidence of malformations of the ThVC, 35S-autoradiography of the ThVC, and the amount of alcian blue-stained cartilaginous matrix. The results showed that on day 11 the synthesis of embryonic MPS was not affected, on day 12 the synthesis of MPS was greatly reduced, on day 13 the synthesis of MPS was slightly reduced while the MPS-content was not affected. On day 13 aplasias were seen in the same percentage as at term, but no fusions were detected. By day 14 the MPS-content was greatly reduced; hyaluronate, condroitin 4-sulfate, and chondroitin 6-sulfate being principally involved; the first fusions were seen. On day 15 the MPS-content was slightly reduced (chondroitin 6-sulfate and heparan sulfate were involved), fusions were complete. The results are discussed in terms of disturbance of structure and function of the notochord and intervertebral discs with the production of fusions, the main type of vertebral malformation in these experiments.
In a study of spontaneous abortions the correlations between karyotype (166 cases), anamnestic data, and macroscopic and histologic findings in placentas (107 cases) and embryos (73 cases) were analyzed. The main results were: 1. The rate of chromosomal aberrations was 39%. Trisomies predominated (60%), followed by monosomy X (20%), triploidies (14%), and structural aberrations (6%). 2. In trisomies a clear prevalence of female sex constitution (2:1) was observed. In normal karyotypes a slight prevalence of females was seen (1.2:1). 3. With increasing maternal age, more trisomies were found in the abortions. 4. Women whose index abortion had a normal karyotype had a history of fewer births but more abortions. 5. Trisomies of acrocentric chromosomes were mainly chorionic sacs with an embryo, while trisomies of the other autosomes resulted in intact empty sacs. 6. The average developmental stage of the embryos was 5 weeks, with a mean gestational age of 14 weeks. Gross malformations were found in 58% of the embryos.
We report almost identical tetramelic monodactyly in two brothers. On the hands and on the feet, only the 5th fingers and the 5th toes were present. Aplastic and hypoplastic defects were found to some degree in the remaining skeletal parts of the hands and feet. All observed deformities were symmetrical. No other defects of either the upper or the lower extremities were found. Both brothers had no other malformation or dysplasias and were apparently of normal intelligence. There were no further cases in the ancestry.
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Three spontaneous abortions with trisomy 2 were analyzed histologically. In one of these, beside chorionic membranes and villi, yolk sac, yolk stalk, body stalk and an embryo are described. Concerning the development stage there seems to be an order; villi and body stalk (16 days), embryo (end of 3rd week to beginning of 4th week) and yolk sac with yolk stalk (2nd half of 4th week).
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