Biomedical subjects
Publications and source records attributed to M Shimada.
It was found that 2,4-di(tert-butyl)-4-(methoxycarbonylmethyl)-2-buten-4-ol ide (II) was formed as an aromatic ring cleavage product of a phenolic lignin model compound, 4,6-di(tert-butyl)guaiacol (I), by laccase of Coriolus versicolor. Based on isotopic experiments with 18O2 and H2 18O, the mechanism of formation of II from I is discussed.
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By the treatment of newborn male rats with monosodium glutamate (MSG), microsomal benzo[a]pyrene hydroxylation, propoxycoumarin O-depropylation, and testosterone (T) 6 beta- and 2 beta-hydroxylations in the adult rats were decreased significantly, while microsomal aniline and T 7 alpha-hydroxylations were increased. However, the treatment of newborn female rats did not significantly alter any of the drug-metabolizing activities examined, except that T 6 beta-hydroxylation and androstenedione formation were slightly increased. The hepatic contents of male-specific cyt. P-450, P-450-male and P-4506 beta, which show high catalytic activities on respective T 16 alpha/2 alpha-, and T 6 beta/2 beta-hydroxylations, decreased in MSG-treated male rats. The level of the female specific enzyme, P-450-female, slightly decreased in the MSG-treated female rats, whereas higher phenobarbital (PB)-induction of PB-inducible isozymes, P-450b and P-450e, was observed in MSG-treated than in control female rats. These results are consistent with the idea that disruption of a pulsatile secretion of growth hormone, which is induced by the neonatal MSG treatment, leads to changes in drug metabolizing activities through the alteration of the levels of sex-specific cyt. P-450s, but also indicate that MSG-treated rats are not an animal model equivalent to hypophysectomized rats.
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The congenital absence of the corpus callosum, a brain anomaly frequently noted in humans, has been recently found to occur in some mice of the ddN strain in our laboratory. In the brains of these mice, the Probst's longitudinal bundle is always present on both cerebral hemispheres. In this research, the neuroanatomical features of the constituent fibers of this bundle were studied by iontophoretical injections of horseradish peroxidase into different loci in the neocortex of acallosal mouse brains. The results revealed that (1) certain cortical fibers of the Probst's bundle terminate in the ipsilateral neocortex; (2) some commissural fibers in the longitudinal bundle originate from the cells in the wide neocortical regions, and project to the opposite hemisphere in homotopic as well as heterotopic regions over the ventral hippocampal commissure; (3) the fibers from different cortical regions are arranged in a topographic manner within this bundle. The present data clearly demonstrate that a good portion of fibers in the Probst's longitudinal bundle seen in the congenitally acallosal mouse brain are corticocortical in nature, which indicates that this bundle has an ipsilateral neocortical association function.
The effect of diethylcarbamazine (DEC) on infective larvae and immature worms of Brugia pahangi was studied in vitro. The in vitro culture of larvae was done using the technique of Mak et al. (1983). In control cultures, most larvae remained alive for 14 days; over 50% survived until day 22 of cultivation. The addition of DEC did not affect the life span of the larvae. Among those which survived for 22 days in control cultures, 77.8% reached the fourth stage, their length being 2908.2 +/- 453.2 microns. When DEC was added to a final concentration of 0.1 mg/ml, the percentage of larvae attaining the fourth stage was reduced (42.9%) and their growth retarded; the length of the fourth-stage larvae was 2548.4 +/- 414.0 microns. The addition of 1.0 mg/ml DEC completely arrested the growth and development of the larvae.
The hemizygote of the macular mutant mice, which is clinically and neuropathologically considered to be a model of Menkes kinky hair disease (MKHD), were injected intraperitoneally four times with 10, 20, 20 and 30 micrograms of cupric chloride on days 4, 6, 8 and 10 after birth, respectively. Their cerebral and cerebellar cortices were chronologically examined by electron microscopy. In the cerebral cortex, only a few abnormal mitochondria with electron-lucent matrix and short peripherally located cristae were scattered in the neurons on day 14, and these had almost entirely vanished after day 21. In the cerebellar cortex, abnormal mitochondria were frequently found on day 14 in the dendrites of the Purkinje cells, whereas they were only occasionally observed in their cytoplasm. Those in the dendrites had decreased in number on day 30, and only a few of them were seen in the cerebellum after day 45. These results show that the copper therapy reduced ultrastructural abnormalities in the hemizygote of this mutant mouse.
This study was undertaken to elucidate the clinical and neuropathological effects of copper administration on the macular mutant mouse. Its hemizygote, which is considered to be a model of Menkes kinky hair disease (MKHD), was injected intraperitoneally four times with 10, 20, 20 and 30 micrograms of cupric chloride on days 4, 6, 8 and 10, respectively. The hemizygote's curly whiskers gradually straightened and the frequent tonic seizures and ataxia disappeared after the injections. The body weight also gradually increased. In the cerebral cortex, the dendritic arborization of the pyramidal neurons in both the normal littermate and the treated hemizygote developed with time and reached the maximum around day 60. In the treated hemizygote, however, the arborization of the dendrites was significantly poor in comparison with that in the normal littermate from day 20 to 90. In the cerebellum of the treated hemizygote, the abnormal Purkinje cells with the few somal sprouts, thick stem dendrite and/or poor arborization, which were seen in the non-treated hemizygote, were improved by day 30, while their focal dendritic swellings remained even on day 60. These results indicate that the copper therapy improves not only the clinical manifestations but also the neuropathological changes, especially in the cerebellum.
The wet weights, contents of DNA, RNA and protein and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) activities were examined in the cerebrum, brain stem and cerebellum from macular mutant mouse, as a model animal for Menkes' kinky hair disease (MKHD). The DNA, RNA and protein contents in the cerebellum from macular hemizygous males (Ml/y) were affected to a much greater extent than those in the cerebrum and the brain stem. This suggests that the main affected part of the brain in Ml/y mouse is the cerebellum. CNP activities in the Ml/y mouse showed a significant decrease in every part of the brain after day 10. This finding may coincide with the changes in myelination in human MKHD.
Characteristics of a typical male-dominant reaction, dealkylation of n-propoxycoumarin, in rat livers were studied in relation to microsomal testosterone 6 beta-hydroxylase. The depropylation was more than 10-fold higher in the liver of male than female adult rats, but the sex-related difference was eliminated by neonatal castration. Hypophysectomy of adult male rats, which decreased the rates of male-specific P-450-male-dependent reactions, increased the depropylation of propoxycoumarin, while the rate was decreased by either intermittent injection or continuous infusion of human growth hormone to hypophysectomized rats. With regard to age-related difference, microsomal depropylation was detectable at neonate and reached a maximal level at 14 to 20 d of age, but was abruptly diminished only in female rats at puberty. These changes are in good agreement with those of testosterone 6 beta-hydroxylation and the content of a male-specific P-450(6)beta-1/PB-1. In reconstituted systems using extracted microsomal lipids, P-450(6)beta-1/PB-1 and P-450-male catalyzed the depropylation of propoxycoumarin. However, the microsomal depropylation was inhibited by antibodies which recognize P-450(6)beta-1/PB-1, but not P-450-male. These results indicate that microsomal depropylation of propoxycoumarin is catalyzed mainly by a male-specific P-450(6)beta-1/PB-1 in livers of untreated rats.
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Phospholipids in high density lipoproteins (HDL) is being used as a negative risk indicator of atherosclerosis. Phospholipids in HDL may not demonstrate the actual level of HDL-phospholipids when determined by the precipitation or ultracentrifugal methods, because HDL fractions contain very high density lipoproteins (VHDL) and albumin. In the present study, the true level of phospholipids in HDL was estimated using high performance liquid chromatography (HPLC), and it was compared with the level of phospholipids in HDL determined by the precipitation method. Sera from 18 healthy subjects were used as materials. In the HPLC method, the HDL fraction was extracted making sure that it contained no free albumin, which is albumin not bound to phospholipids. The HDL fraction was separated into subfractions. It was found that phospholipids in the VHDL fraction make a 20.2 +/- 7.3% (mean +/- S.D.) part of the total HDL-phospholipids. A large part of the VHDL fraction was constituted of albumin-bound phospholipids. A significant correlation was observed between HDL-phospholipids determined by the precipitation method, which contain albumin, and the actual HDL fraction phospholipids determined by HPLC, which do not contain VHDL (r = 0.903, p less than 0.01). These results suggest that HDL-phospholipids values determined by the precipitation method give useful clinical data.
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From June 1982 to May 1986 in a small village in Kwale, Kenya, we studied seasonal fluctuations in populations of Bulinus globosus, prevalence of Schistosoma haematobium infection in this snail, and effects of chemotherapy and piped water supply on infection rate of snails. In the perennially-flowing Pemba River, relatively small numbers of snails were collected; they were found only during the hot dry season (December to March). In a tributary stream, the Kadingo River, whose flow ceased at the end of both the cool and hot dry seasons, snail numbers peaked at the end of the cool dry season (October to November) and at the beginning of the hot dry season (January). Large numbers of infected snails were found in the Kadingo River from November to January (short rainy season and beginning of dry season). Selective mass chemotherapy with metrifonate and provision of piped water were begun in February and March 1984. These control measures achieved a significant reduction in the infection rate of snails (P less than 0.001); the annual infection rate for the 2 years before treatment was 9.3% and 13.1%, and for the 2 years after treatment was 3.5% and 3.4%.
In a community in Kwale district, Kenya, selective mass chemotherapy with metrifonate caused a marked reduction in the intensity of Schistosoma haematobium infection from 46.5 to 9.4 eggs/hr and a sharp fall in prevalence of gross hematuria from 18.3% to 5.1%, although overall prevalence was reduced only slightly from 67.4% to 54%. The effect of metrifonate on cure rate and reduction of infection intensity was limited by both age and pretreatment infection intensity. Rate of improvement from gross hematuria was similar in all ages and in all classes of intensity of infection. Two doses of metrifonate reduced the prevalence of gross hematuria as much as 3 doses did, while the effect of a single dose on morbidity remains to be clarified.
The control of intra- and postoperative hemorrhage is as significant a problem following prostatectomy as postoperative urinary tract infection. We made a trial use of a solution of thrombin in continuous bladder lavage to control postoperative hemorrhage. A group of 21 patients with benign prostatic hyperplasia were treated by the thrombin lavage, with a group of 20 similar patients as controls. The treated group comprised 5 patients operated on by suprapubic, 11 by retropubic and 6 by transurethral prostatectomy, and the control group consisted of 6 patients operated on by suprapubic, 8 by retropubic, and 6 by transurethral prostatectomy. The thrombin lavage was, as a general rule, performed by lavaging the bladder with a solution of thrombin in physiological saline containing 100 units in each ml through an indwelling 3-way Foly catheter continuously for 24 hours following operation. There was no significant difference in the duration of macroscopic hematuria following operation by any operating technic between the control and the treated grove. The duration of microscopic hematuria was significantly shorter in the patients operated on by suprapubic prostatectomy and treated with thrombin than in the control group similarly operated on, and also tended to be reduced in the patients operated on by retropubic prostatectomy and treated with thrombin, compared with the controls similarly operated on. There was no significant difference in the duration between the patients operated on by transurethral technic. No particular adverse reactions to the thrombin lavage were observed.
The possibility of involvement of calcium ions in the hatching of Schistosoma mansoni eggs in water is described. The hatching of S. mansoni eggs under low osmotic pressure was partially inhibited by EGTA (5 mM), lanthanum chloride (1-5 mM), and ruthenium red (0.1-1 mM). The reagents used in these experiments were not toxic to the eggs however, because miracidia hatched normally when the reagents were removed.
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