[Wilm's tumor in multilocular cysts of both kidneys].
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Biomedical subjects
Publications and source records attributed to T Toda.
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The effects of trans-fatty acid-rich and saturated acid-rich diets on the fatty acid composition and morphology of swine arterial tissues were studied. Three groups of two-month-old swine were fed either a basal diet or a basal diet containing 8.3% margarine or butter for 4 months. The most significant change observed in the fatty acid pattern was the accumulation of 18 : 2 omega 6 and the suppression of both 20 : 4 omega 6 and 22 : 4 omega 6 acids in the aortic tissues of swine fed either butter or margarine as compared to swine fed the basal diet. Also, omega 6 metabolites were significantly decreased in swine fed diets containing butter or margarine, as compared to those fed a basal diet. The group of swine which were fed either butter or margarine containing diets suffered a significant increase in intimal thickening of the coronary artery compared to those fed the basal diet. These thickened intima were characterized by the presence of modified smooth muscle cells, lipid containing cells, and degenerated cells without stainable lipids. However, there was no significant difference in the incidence and extent of intimal thickening of the coronary arteries between swine fed either of the two fat containing diets.
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Thirteen recessive cold sensitive nuclear division arrest mutants were isolated from the fission yeast Schizosaccharomyces pombe. Twelve unlinked genes were defined; six in chromosome I, three in chromosome II and two in chromosome III. The map positions of three nuclear division arrest genes (nda1, nda2 and nda3) in chromosome II were determined precisely. Together with the previously obtained temperature-sensitive cell division cycle mutations, at least 20 genes appear to control the nuclear division of the fission yeast. Physiological studies indicated that most cold sensitive nda mutants incubated previously at 22 degrees C proceeded with a synchronously normal cell-cycle after temperature shift-up. The morphology of the nuclei and nuclear chromatin region was studied by the 4',6-diamidino-2-phenylindole staining method and by electron microscopy. Each mutant exhibited characteristic nuclear morphology at 22 degrees C, showing the specific blockages. The nda genes seem to control a pathway of structural alterations in the nuclear chromatin region with the order hemisphere, condensed ellipsoid, segregating U-form and separating hemispheres. Two genes, nda2 and nda3, pleiotropically control nuclear division, nuclear location and cell shape. The terminal phenotype of nda2-KM52 is characterized by the nuclear displacement, the absence of a spindle and abnormal locations of spindle pole bodies. The cells of nda3-KM311 were aberrant in shape and contained a partially separated chromatin region with a long spindle. Together with the results of the accompanying paper, we conclude that nda2 and nda3 genes control nuclear and cytoplasmic microtubular organization.
Two genes, nda2 and nda3, previously defined by cold sensitive nuclear division arrest (nda) mutations in the fission yeast Schizosaccharomyces pombe were studied. A mutant nda2-KM52 was found to be supersensitive (at the permissive temperature) to the tubulin-binding drugs such as thiabendazole, methylbenzimidazol-2yl carbamate and nocodazole. A single mutation in nda2 appears to cause both drug supersensitivity and cold sensitivity. The defective phenotypes of nda2-KM52 with a low concentration of the drugs were characterized by nuclear displacement and anomalously situated spindle pole bodies. The allele of the other mutant, nda3-KM311, was sh216 to be linked closely to the ben1 locus, which determines resistance to the drug. The identity of ben1 and nda3 genes was proved by a newly isolated mutant ben1-TB1005; it manifests ben1 resistance and the cold sensitive nda3 phenotype. At 22 degrees C, ben1-TB1005 showed cell branching and deformation characteristic of nda3-KM311. Eleven mutants supersensitive to thiabendazole were newly isolated by replica plating. Four strains were mapped in nda2, while the other four were in nda3. Most of the isolated mutants were blocked at nuclear division in the presence of a low concentration of the drug. Thus, the products of genes nda2 and nda3 (ben1) interact directly or indirectly with the drugs and control, in different ways, microtubular organization in the cells of S. pombe.
We studied serum acute phase reactant (APR) levels in 45 pediatric surgical patients. Alpha 1-acid glycoprotein (alpha 1-AG) showed a peak value on day 3 postoperatively (P.O.) and alpha 1-antitrypsin (alpha 1-AT) showed a high value on days 3-5 P.O. These glycoproteins returned to normal levels by day 21 P.O., but the level of haptoglobin (Hp) remained high until day 21 P.O. The postoperative changes of alpha 1-AG and alpha 1-AT correlated with the process of recovery from inflammatory conditions, but C-reactive protein (CRP) reached a peak on days 1-2 P.O. and returned to normal limits by day 14 P.O. In patients with infection, CRP returned to the normal level rapidly before recovery from infection. Of the 3 glycoproteins, alpha 1-AG seemed to be a valuable indicator of the pathological conditions. Postoperative changes in APR levels should be useful for early detection of postoperative complications. Persistent ileus led to an increase in APR levels, as a consequence of an inflammatory reaction due to breakdown of the intestinal mucosal barrier.
Fibromuscular intimal thickening was seen in the ascending and thoracic aorta of the swine fed 62,500 IU of vitamin D3/kg of diet for three months duration; and after 3 months of vitamin D3 withdrawal, atherosclerotic lesions were found. In rabbits, pronounced aortic smooth muscle cell necrosis developed with the forced feeding of 10,000 IU vitamin D3 dissolved in corn oil/kg body weight/day for 14 days. Serum analyses indicated that blood calcium did not differ from that of animals fed corn oil alone, but that the level of serum 25-hydroxy-vitamin D3 measured by HPLC was 30 times that in the control animals. These data suggest that choleclaciferol (the oxidized sterol with vitamin D3 activity) has a very destructive influence on the integrity of arterial wall, and that smooth muscle cell necrosis could be caused by enhanced membrane permeability to Ca2+ following 25-hydroxy-vitamin D3 incorporation into smooth muscle cell membranes.
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The major ovarian hormones (estradiol and progesterone), the major testicular hormone (testosterone), and the major precursor to steroid hormones (cholesterol) were fed ad libitum in various combinations for either 2 weeks or 2 months (56 days) to 5-day-old female chicks; the effects of these treatments on liver lipids and plasma lipoproteins were measured. After two weeks, chicks fed basal diet supplemented with 0.05% estradiol had significant increases in plasma total cholesterol, triglycerides, and phospholipids (P less than .01). The combined supplementation of 0.05% estradiol plus 1% cholesterol produced an additive increase in plasma total cholesterol resulting in levels higher than obtained by either treatment alone (P less than .01). The addition of 0.2% progesterone to the 1% cholesterol diet inhibited the accumulation of plasma cholesterol (P less than .05), liver cholesterol (P less than .01), and liver triglycerides (P less than .01), which were found in comparable animals fed only 1% cholesterol. Likewise, the addition of 0.2% progesterone to diet containing 0.05% estradiol inhibited (P less than .01) accumulations in all of the plasma lipid classes which were found in comparable birds fed only 0.05% estradiol. After 2 months feeding, 0.1% testosterone had no effect on plasma or liver lipids. The combination of 0.05% estradiol plus 0.1% testosterone for 2 months was not very effective in reducing the hyperlipidemia caused by estradiol alone, but this treatment did result in a peculiar dwarf chicken. The results demonstrate strong steroid sex hormone interactions which produce major changes in chick plasma and liver lipid metabolism.
The effects of levamisole used in combination with Mitomycin C and Tegafur in patients with resectable stomach cancer were investigated in 10 cooperative institutes. The patients were randomly allocated to the treatment with either control or levamisole by envelope method. Levamisole group was treated with Mitomycin C (day 0, 20 mg, day 1, 10 mg, one shot i.v.), Tegafur (600 mg/day, p.o.) and levamisole (150 mg/day, p.o.). Levamisole was administered 3 consecutive days prior to surgery, and 3 consecutive days every fortnight after surgery. The control group was administered Mitomycin C and Tegafur. The both drugs were administered by the same method as above. Two hundred and twenty-two patients were entered in this trial. However, with the exclusion of 67 patients, the eligible patients were 155, consisting of 77 in the control group and 78 in the levamisole group. In stage III patients, the disease-free interval and survival time were significantly prolonged in the levamisole group compared to the control group (generalized Wilcoxon test p less than 0.05). The side effects were observed a little more frequently in the levamisole group. However, there was no significant difference. From this result, it can be considered that levamisole is effective in delaying recurrence and in prolonging survival time of the patients when used in combination with adjuvant chemotherapy after resection of stomach cancer.
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Degenerative changes in endothelial and smooth muscle cells from fetal, 2-month-, and 6-month-old swine ductus vasculature were observed. In fetal ductus, a discontinuous internal elastic lamina and increased extracellular mucopolysaccharide deposition were initially noted. At 2 months of age, there was widespread fibromuscular intimal thickening, the appearance of modified smooth muscle cells, increased medial fibrosis, and the occurrence of cell debris and nuclear pyknosis. Early modification of smooth muscle cells was marked by increased occurrence of lysosomes, widely dilated rough endoplasmic reticulum, and Golgi bodies. Abundant aggregates of Weibel-Palade bodies occurred in early endothelial cell degeneration. At 6 months of age, after complete anatomical closure, there was abundant lipid vacuole production by degenerated medial smooth muscle cells. This study demonstrates that at various stages of occlusion, endothelial and smooth muscle cells from ductus vasculature exhibit morphological changes which are qualitatively similar to atherosclerosis.
Five-day-old female chicks were fed diets containing testosterone, estradiol, and cholesterol for 2 months. Cholesterol supplementation of 1 per cent. resulted in production of lipid vacuoles in the interlamellar connective tissue cells and to a lesser extent in the smooth muscle cells in the aorta; cholesterol had no effect on the coronary artery. The vasculo-toxic nature of estrogen was indicated when 0.05 per cent. dietary estradiol produced more accumulations of lipid vacuoles in smooth muscle cells, more extracellular lipid, and more smooth muscle cell death than cholesterol feeding. A dietary combination of cholesterol plus estradiol produced severe lipid deposition throughout the entire thickness of ascending aorta, and degenerative atherosclerotic changes in the coronary artery. Combined testosterone and estradiol supplementation resulted in peculiar dwarf chickens which exhibited increased vascular smooth muscle cell mitosis and degeneration.
The clinical and pathological features of congenital multicystic dysplasia of the kidney are reviewed and we report of a patient with bilateral dysplasia who lived longer than do most such patients. When multicystic disease of the kidney is bilateral, it is commonly confused with polycystic disease. Despite the fatal prognosis, differentiation is essential for appropriate genetic counselling since multicystic disease is not a familial occurrence.
The pharmacokinetics of lisuride hydrogen maleate (LHM) were investigated in rat, rabbit and rhesus monkey. Experiments were designed to meet not only the requirements of drug registration but also to serve other preclinical disciplines (toxicology, pharmacology). LHM is absorbed almost completely at a dose level of 100-250 micrograms/kg. During absorption and first liver passage (FPE) LHM is metabolized. The FPE was highest in the rhesus monkey and lowest in the rat. Calculated on bioavailability during chronic tolerance studies, in the highest dose group rats were burdened with 180-fold and rhesus monkeys with 70-fold the highest human dose (parkinsonism). Total clearance values indicated the presence of extrahepatic metabolism in all animal species. Terminal half-lives of unchanged drug in plasma were in the range of a few hours. Therefore, no accumulation of unchanged drug was expected to occur following daily repeated administration in the animal species investigated. Elimination of 14C-radioactivity proceeded mainly via the liver in rat and rabbit. The rhesus monkey excreted most of the dose administered in the urine. Enterohepatic circulation of 14C-material was demonstrated in the rat. In the rat but not in the other two species a small part of the dose (about 2%) accumulated in blood cells in the form of metabolites. Unchanged lisuride is able to cross membranes very rapidly, this was shown in distribution studies (whole-body autoradiography of rat, direct measurements in rat and rabbit). Transfer of lisuride into fetuses and brain is governed by its concentration in plasma. Drug level decrease in fetuses and brain was shown to somewhat slower than in plasma. Detailed evaluation of the distribution pattern in the brain of rat and rabbit showed a high affinity of lisuride for its preferential target tissue, the pituitary.
Video-connected fluorescence microscopy was introduced to study the yeast nuclear chromatin region. It was defined as the nuclear area where a DNA-binding fluorescent probe 4',6-diamidino-2-phenylindole specifically bound and fluoresced. The 3-dimensional feature of the mitotic chromatin region was deduced by analysing the successive video images of a cell viewed at different angles. By investigating synchronous culture of the wild-type fission yeast Schizosaccharomyces pombe, we found sequential structural alterations in the chromatin region during mitosis. The steps found include the compaction of the chromatin region from the regular hemispherical form, the formation of a U-shaped intermediate and the rapid segregation into 2 daughter hemispherical forms. Six cs cdc mutants, apparently blocked in mitosis, were observed by fluorescence microscopy. Under the restrictive conditions their chromatin regions exhibited either hemispherical, compact, disk-like, U-shaped or partially segregated chromatin regions. Two mutants showed anomalous nuclear locations. The results of the temperature shift-up experiments of the highly reversible KM52 and KM108 strains supported the above scheme of sequential alterations in the chromatin region.
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