A new mutant gene that causes preaxial polydactyly in the hindlimbs was found in the strain of rats with fused pulmonary lobes (fpl). Genetic analysis has revealed that the new mutation is inherited as an autosomal recessive trait and is not closely linked with the fpl gene. Since homozygous mutants die within the first 2 days after birth, the mutant gene was named polydactyly lethal, gene symbol pl. A test for allelism between the pl gene and another gene, pd, which also causes preaxial duplication anomalies, showed no allelism between these two genes. Skeletal examination revealed that all pl/pl newborns had thickening and/or bifurcation of tarsal I and metatarsal I, as well as duplication of the proximal and distal phalanges of digit I in the hindlimbs. In some cases, phalangeal duplication or bifurcation in digit I with thickening of metacarpal I was also found in the forelimbs, although extra forelimb digits were not detected externally. The pl/pl newborns showed hunchback-like abnormal posture externally and had several associated vertebral abnormalities in varying degrees, i.e., kyphosis, scoliosis, splitting of the thoracic vertebral bodies, and fusion of the lumbar vertebral bodies. No major malformations were seen in the visceral organs. The cause of neonatal deaths has not yet been determined.
A 67-year-old male was admitted to our hospital because of lung cancer and interstitial pneumonia. Cisplatin, vindesie and mitomycin C were administered for treatment of lung cancer. The leucocyte-counts declined to 1700/μl on the eighth day after the chemotherapy. Though granulocyte colony-stimulating factor was administered, pain in the right thigh and high grade fever developed. Because Staphylococcus aureus was isolated from the blood specimen, piperacillin was administered. But the high grade fever continued and the pain was expanded to the right hip, left hip, thigh and leg. Because a computed tomograph of the lower limbs showed low density areas in bilateral gluteus maximus muscle right adductor magnus muscle, left biceps femoris muscle and left soleus muscle and the culture of an aspirate from abscess of right leg detected S. aureus, multiple muscular abscesses of the lower limbs was confirmed. We changed the antibiotics from PIPC to imipenem/cilastatin and minocycline on nineteenth day after the chemotherapy. His symptoms improved after the change of antibacterial agents. But he died of acute exacerbation of interstitial pneumonia, after about two months of the chemotherapy. Muscular abscesses of the limbs are very rare in Japan. Only four cases with muscular abscess of the limbs were reported in Japan, since 1988. This case suggests that a muscular abscess must be considered in the differential diagnosis of fever in patients with neutropenia.
Teratogenic potential of ethylenethiourea (ETU) was investigated in SLC-ICR mice after its reaction with sodium nitrite. ETU was given orally in doses of 400 mg/kg on various days of pregnancy in combination with 200 mg/kg NaNO2 at varied intervals. When NaNO2 was given to females immediately after their treatment with ETU on day 6 or 8 of pregnancy, fetal survival was significantly decreased. Various types of malformations were observed in the living fetuses from mothers treated on day 6, 8, or 10 of pregnancy, but not on day 12. The teratogenicity disappeared when NaNO2 was given 2 h after the treatment with ETU.
PD strain male rats that carry an autosomal recessive gene, preaxial duplication (gene symbol: pd), are sterile in the homozygous condition (pd/pd) due to a spermatogenic breakdown in the process of spermatogenesis at the spermatocyte and/or spermatid stage(s), although heterozygotes (pd/+) are normal. In this study, pd/pd males were examined for the presence of abnormal association of the sex chromosomes that might lead to spermatogenic breakdown. Light and electron microscopic observations of the chromosomes at meiotic prophase and metaphase in primary spermatocytes revealed several types of abnormal X-Y association and configurations in pd/pd males. However, the incidences of the abnormal configuration were comparable to those in pd/+ males. These results suggest that abnormal X-Y chromosome association in the germ cells is not a significant cause of spermatogenic breakdown in pd/pd males.
ABSTRACT The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of p, p '‐DDT in general accordance with the improved Japanese MAFF guidelines (12‐Nousan‐No. 8147,2–1–18, 2000). p, p '‐DDT suspended in 1% aqueous solution of CMC was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,5, 25, or 100 mg/kg/day and to pregnant KbI: JW rabbits on GD 6–27 at a dose of 0,5,20, or 80 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs. Adverse effects on maternal animals were found only at the highest dose in both species; i.e. , clonic convulsion (2/24 in rats, 5/22 in rabbits), mortality (1/24 in rats), abortion or premature delivery (4/22 in rabbits), and reduced body weight gains and food consumption. However, the control and treated groups showed comparable values for the numbers of corpora lutea and implants, percent preimplantation losses, number of live fetuses, percent resorptions and fetal deaths, sex ratio, fetal body weights, and placental weights in both species, and anogenital distance and testicular histology in rats. Although fetal examination revealed slightly increased incidence of 27 presacral vertebrae in the highest dose group in rats, there was no treatment‐related increase in the incidence of malformations in any of the species. Based on these results, it is concluded that p, p '‐DDT causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in an increased incidence of skeletal variations in rats at a maternally toxic dose.
Ethylenethiourea (ETU) is a specific neuroteratogen that induces communicating hydrocephalus ex vacuo at oral doses far lower than those that cause any observable toxic sign or 50% death (LD50) in the rat dam. The teratogenic activity appears to be related to ETU itself and not to its metabolites. It is dependent upon the presence of an imidazolidine ring with a specific molecular location of sulfur atom. It is unlikely that ETU-induced alterations in thyroid function or thyroxine levels in the maternal rat are involved in teratogenic activity. The initial target following maternal dosing with ETU is the primitive neuroblast that undergoes necrosis, but the subsequent changes leading to the development of hydrocephalus are not clear. Teratogenicity studies in hamsters, mice, guinea pigs, rabbits, and rats revealed that ETU either required extremely high doses to produce malformations or was ineffective. The results of various distribution studies are summarized. Further, investigations dealing with exposure to ETU in the general population and in exposed workers in the rubber industry as well as those involved in the manufacture and spraying of fungicides are discussed briefly with reference to reducing the exposure levels.
