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Biomedical subjects

J Kawada

Publications and source records attributed to J Kawada.

At least 37 records · Page 2Linked to original sources
PubMed1992

A binding profile of manganese to the nucleus of rat liver cells, and manganese-induced aberrations in thyroid hormone content and RNA synthesis in the nucleus.

Manganese (Mn) is accumulated in the nuclear and mitochondrial fractions when excess Mn is administered. However, little is known with respect to the behaviors of Mn in nuclei. In the present study, rats were given excess Mn and the nuclei were purified from liver cells by differential and sucrose gradient centrifugations. Being subjected to equilibrium dialysis with a radioactive 54Mn, the binding capacity of Mn in nuclei from the control rat was five-fold higher than BSA, which was used as a reference protein; and the capacity of 54Mn-binding rose in the nuclei from the Mn-treated animals in comparison with those from the control. On the analyses of nuclear materials with partial solubilization, sepharose column chromatography and HPLC, there were two major fractions which associated with a lot of Mn; one fraction was of large molecules of DNA, and the other fraction seemed to be peptides with small molecular weights. Therefore, Mn may open up a superhelical structure of DNA to provide more negatively charged phosphate moiety as a binding-site for a positively charged Mn. The results also disclosed a possible aberration in biological functions due to excess Mn in nuclei; the apparent association constant of triiodothyronine, a physiologically active thyroid hormone, to the nucleus was reduced by 75% and the uptake of 14C-labelled orotic acid to a newly synthesized RNA in the liver was severely inhibited.

Animals↗
PubMed1991

Upbeat nystagmus: clinicopathological and pathophysiological considerations.

We describe an electro-oculographic study of upbeat nystagmus in 4 patients, with neuropathological correlation in one. All patients had lesions in the pontine tegmentum. The electro-oculographic data may be explained by imbalanced vertical vestibular or smooth pursuit eye movement control. The nystagmus stopped or reversed direction during convergence or in supine head positions. We propose that changes in the intensity or direction of upbeat nystagmus that are induced by convergence or changes in head position, are caused by vertical imbalance in the otolithic-ocular reflex, when superimposed on an imbalanced vestibulo-ocular reflex (VOR). Imbalance of the otolithic-ocular reflex and the vertical VOR are caused by damage in the pontomedullary tegmentum.

Adult↗
PubMed1991

Effect of bupivacaine on muscle tissues and new bone formation induced by demineralized bone matrix gelatin.

Heterotopic bone formation induced by demineralized bone matrix gelatin (BMG) in bupivacaine-HCl-treated skeletal muscle was examined histologically. BMG was obtained by dehydrating diaphyseal shafts of femora and tibiae of male, 4-week-old Sprague-Dawley (SD) rats, cutting it into chips, and demineralizing and extracting the chips with various solutions. The BMG was implanted into the rectus abdominis muscle of male, 5-week-old SD rats, bupivacaine-HCl was injected at the same site, and the resulting plaques of tissues were examined histologically on days 5, 10, 15 and 20 after BMG implantation. Heterotopic bone formation occurred in all animals. The bupivacaine-treated group had more degenerated and injured muscle fibers, and more osteocytes than the control group. Electron microscopy showed that the basement membrane of muscle fibers was discontinuous and that many mononucleated cells resembling activated satellite cells were present on day 5. Many fibroblasts, undifferentiated mesenchymal cells and myogenic cells were seen in the area around the BMG. In new bones there were few osteocytes on day 10, but their numbers were increased on days 15 and 20 after implantation, especially in the bupivacaine-treated group. The population of osteocytes that increased rapidly may have included mononucleated cells similar to activated satellite cells.

Abdominal Muscles↗
PubMed1991

Differential effects on fatty acid compositions in the liver microsomes of thyroidectomized or streptozocin induced diabetic rats.

The purpose of the present study was to locate a controversial site and to make generalizations about the effects of thyroidectomy (Tx) and streptozocin (STZ) on the distribution pattern of an individual fatty acid in microsomal fractions of the animals thus treated. The results obtained were compared with the reported data. The effects of Tx on C18:1, C18:2, and all detectable C20 and C22 species harmonized well within each species; however the effects of Tx on C16 species and C18:0 varied within each species. Meanwhile, all the effects of STZ were identical within the species, but were often in opposite directions between two adjacent species; e.g. C18:0 and C18:1. These findings strongly indicate that desaturation and elongation sites were independently affected by either Tx or STZ. The comparison suggested that controversial effects appeared in the distribution proper to species C18. Therefore, delta 9-desaturase activity in the microsomal fractions was measured, using stearoyl coenzyme A (CoA) as substrate, resulting in some partial reduction in Tx, but complete suppression in STZ-treated animals. The total contents of phospholipid and cholesterol in the microsomes were also measured. Results showed a significant increase in microsomes within the STZ-group, but almost no change in the Tx-group, indicating that the changes in an individual fatty acid component and in the total fatty acids do not always take place in parallel.

Animals↗
PubMed1991

Uptake of nicotinamide by rat pancreatic beta cells with regard to streptozotocin action.

Exposure of rat pancreatic beta cells in monolayer culture to 2 mmol streptozotocin (STZ)/l for 1 h followed by thorough washing inhibited their uptake of [14C]nicotinamide and [3H]2-deoxyglucose [( 3H]2-DG) to about 50% and also reduced the intracellular ATP concentration to 50% of that in control cells. These changes were not due to a lethal cytotoxic effect of STZ, because cell viability, as estimated by succinic dehydrogenase activity, was 90% of that of control cells. Oligomycin and carbonylcyanide-m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, caused a dose-dependent decrease in intracellular ATP concentration while maintaining high cell viability. These ATP-depleted cells showed a decrease in insulin release and an inhibition of the uptake of [14C]nicotinamide and [3H]2-DG in a dose-dependent manner. Therefore oligomycin and CCCP reproduced the same effects as those found in beta cells treated with STZ. These results suggest that the uptake of nicotinamide and 2-DG by beta cells might be regulated by their intracellular ATP concentration. The decreased uptake of nicotinamide in ATP-depleted beta cells caused by STZ might explain the lack of protective effect of nicotinamide against STZ cytotoxicity when administered after the latter. Furthermore, the radiotracer experiments demonstrated that the transport of nicotinamide by intact beta cells was inhibited in a dose-dependent manner by 2-DG and vice versa, i.e. the transport of 2-DG was inhibited by nicotinamide. These findings suggest the existence of a common transport mechanism in beta cells responsible for the uptake of nicotinamide and 2-DG, the transport of which is known to occur by facilitated diffusion.

Adenosine Triphosphate↗
PubMed1991

The ultrastructure of cartilage formation from neonatal skeletal muscle in vitro.

Histological changes in cultured neonatal skeletal muscle tissue at the early stage of cartilage induction by syngeneic insoluble bone matrix gelatin (BMG) containing bone morphogenetic protein were examined by light and electron microscopy. Minced skeletal muscle was cultured on hemicylindrical pieces of BMG for 14 days. Chondroblasts first appeared in the crevices of the BMG on Day 7 of the culture, and cartilage tissue was seen to fill the crevices completely by Day 10. The main findings in this work are as follows: 1) the activation of satellite cells and necrosis of myonuclei; 2) the migration of satellite cells from the basement membrane; 3) fibroblasts with increased numbers of organelles between degenerated muscle fibers closely resembling the migratory satellite cells; 4) the migration of the spindle-shaped cells into the crevices of the BMG; and 5) change of the spindle-shaped cells to chondroblasts. These findings suggest that neonatal skeletal muscles, which appear more mature than embryonic muscles, also have a chondrogenetic potential when grown on BMG, and that chondroblasts originate from the spindle-shaped cells which are thought to result from migratory satellite cells as well as fibroblasts.

Animals↗
PubMed1991

Primary position upbeat nystagmus. Clinicopathologic study of four patients.

We report an electro-oculographic study (EOG) of upbeat nystagmus and neuroradiological correlations in 4 patients and neuropathological findings in 1 patient. All 4 patients revealed responsible lesions in the lower pontine tegmentum. The EOG data suggest that our patients had a deficit in vertical smooth eye movement balance. The nystagmus stopped or reversed direction during convergence or changes of head position. These EOG findings might be caused by vertical imbalance in the otolithic ocular reflex, superimposed on an imbalanced vestibulo-ocular reflex (VOR), secondary to a damage to the pontomedullary tegmentum.

Adult↗
PubMed1991

Architecture of implanted bone matrix gelatin influences heterotopic calcification and new bone formation.

Heterotopic bone formation in skeletal muscle induced by compacted demineralized bone matrix gelatin (BMG) was studied histologically and biochemically. BMG was obtained by dehydrating diaphyseal shafts of femora and tibiae of 4-week-old male Sprague-Dawley rats, cutting the bone into chips, and demineralizing and extracting the chips with various solutions. The BMG was treated with 4 M guanidine-HCl, and compacted BMG was prepared by centrifugation. The compacted BMG was implanted into the rectus abdominis muscle of 5-week-old male Sprague-Dawley rats. The resulting specimens were examined histologically, and their alkaline phosphatase activity and the calcium content of the tissues were measured 3, 5, 7, 10, and 15 days after implantation. The BMG (separated BMG) with 75- to 500-microns particle sizes were implanted into control rats. The results showed that calcification, alkaline phosphatase activity, and bone formation were suppressed by implantation of the compacted BMG and that scarcely any vascularization occurred. Calcification, vascularization, and alkaline phosphatase activity were related and were indispensable for bone formation. In the control group, bone formation was observed at sites of high activity of alkaline phosphatase and well-developed vascularization. These results suggested that compacting of BMG suppressed vascularization, decreased calcification, and consequently reduced the induction of bone formation.

Alkaline Phosphatase↗
PubMed1991

Changes in stainability observed by light microscopy in the brains of ataxial mice subjected to three generations of manganese administration.

Two neonates of mice which manifested abnormal motions in their gait in the third generation litter, following the start of manganese (Mn) administration, were selected. One was severely affected by Mn and the other was only moderately affected. Various regions in the brains of the neonates were subjected to histochemical examination under a light microscopy. The losses of stainability in granular cells in the external layer of the cerebral cortex, and Purkinje cells in the cerebellar cortex, and the increase in stainability of the nerve fibers in the cerebellar medulla were in parallel to the degree of abnormal movement in the gait; the greater loss or gain in stainability, varying according to the regions, was associated with the more severe damages to motion. Meanwhile, the changes in the stainabilities of nerve cell nuclei in the lamellar structure of cerebral motor areas and the Nissl bodies in the cerebral medulla were already maximal in the moderately affected neonate. These results indicate that the Mn effect covers a broad area of the extrapyramidal tract even though there are some differences in the sensitivity to Mn in different regions.

Animals↗
PubMed1991

Synergistic and antagonistic effects on fatty acid composition in the liver mitochondria of rats by thyroidectomy and streptozotocin-administration.

The content of individual fatty acid component in mitochondria of livers from thyroidectomized (Tx) and streptozotocin (STZ)-induced diabetic rats was measured to investigate how different hormones are interrelated to control the amount of a particular fatty acid in mitochondria. The results showed (1) diabetes, in general, affected fatty acid contents more severely than hypothyroidism, regardless of the direction of the changes; (2) Hypothyroidism and diabetes affected antagonistically the contents of C16 species and C18:1, which belong to a de novo synthesis (oleate series). However, the two pathological conditions affected synergistically those of higher unsaturated species, eg. C18:2, C20:3 and C20:4, which belong to a dietary-dependent synthesis (linoleate series). These results strongly indicated that each desaturation site and elongation site is affected in a preferential order by either thyroid hormone or insulin, and that hypothyroidism and diabetes have their effects differently on the process of de novo synthesis and the pathways initiated from an essential fatty acid in mitochondria.

Animals↗
PubMed1991

Changes in mouse brain monoamine oxidase activity in the first, second and fourth generations after manganese administration.

The present study was conducted to explore whether or not manganese effect on brain monoamine oxidase (EC 1.4.3.4) is subject to hereditary genetic amplification. Mice of both sexes were given manganese through four generations, and the enzyme activity was measured in the cerebral cortex, cerebellum, hypothalamus and hippocampus of each of the generations except for the third, whose activity we were not in a position to measure. Intrinsic enzyme activity was highest in the cerebellum, and was followed by those in the cerebral cortex and hypothalamus. The activity in the hippocampus was the lowest. Manganese administration greatly stimulated the activity in the cerebellum. However, as generation succeeded, the level of susceptibility to manganese gradually declined. Manganese concentration in pooled suborgan fractions proved to be, in every case, higher in the cerebral cortex, cerebellum and hippocampus and lower in the hypothalamus. No indication was found that the manganese effect is genetically inherited.

Activation Analysis↗
PubMed1991

Muscle tissue reactions to implantation of bone matrix gelatin.

Histologic changes of muscle tissue in the early stage of heterotopic osteogenesis induced by syngeneic insoluble bone matrix gelatin (BMG) with bone morphogenetic protein in rats was observed by light and electron microscopy. BMG induced cartilage in muscle tissue by Day 7 after its implantation, woven bone by Day 10, and lamellar bone with bone marrow by Day 14. The new findings in this work include (1) the disappearance of the basement membrane of muscle fibers; (2) the activation of the satellite cells of muscle fibers; (3) the appearance of fibroblastlike cells that closely resembled activated satellite cells among the degenerated muscle fibers or on the surface of the BMG; and (4) the change of fibroblastlike cells to chondroblasts or osteoblasts. These findings suggest that intramuscular implantation of BMG caused the conspicuous disappearance of the basement membrane of the muscle fiber and may play a part in osteogenesis induced by BMG.

Animals↗
PubMed1991

Subperiosteal implantation of bone morphogenetic protein adsorbed to hydroxyapatite.

Bone development was induced by bone morphogenetic protein (BMP) adsorbed to hydroxyapatite (HAP) under the periosteum of rat parietal bone. The BMP was isolated by Sephacryl-S200 column chromatography after passage through a membrane filter system. The yield of the fraction with BMP activity was 20 times greater than yields obtained by conventional methods. BMP was adsorbed to HAP in vacuo. HAP alone was implanted as a control. The formation of cartilage and bone was observed seven days after the implantation of BMP-HAP, and the newly formed bone fused with the host calvaria after 28 days. In control rats, no bone formation was seen within 56 days after implantation. The BMP-HAP complex was more effective in induced periosteal bone formation than HAP only.

Adsorption↗
PubMed1990

Acute effects of anticonvulsants on brain-stem auditory evoked potentials in rats.

Acute effects of various anticonvulsants on brain-stem auditory evoked potentials (BAEPs) in rats were tested. A high dose of phenytoin abolished all BAEP waves. Carbamazepine increased all 4 wave latencies. Phenobarbital and clonazepam increased the latencies of waves IV and III. Therefore, if BAEPs are to be used as an ancillary test for brain death, the possibility of significant effects of high dosages of anticonvulsants on BAEPs must be considered.

Acoustic Stimulation↗
PubMed1990

Allopurinol protects pancreatic beta cells from the cytotoxic effect of streptozotocin: in vitro study.

Isolated rat pancreatic beta cells in monolayer culture were shown to be protected from the cytotoxic effect of streptozotocin (STZ) by allopurinol. Pretreatment with allopurinol for 2 h caused dose-dependent inhibition of the decreased secretion of insulin by the cells induced by STZ (2 mM, for 1 h), 500 microM allopurinol causing complete inhibition of this effect of STZ. Pretreatment with allopurinol (250 microM) also prevented the rapid decrease in intracellular adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide concentrations in beta cells induced by treatment with STZ. High performance liquid chromatography revealed that the intracellular concentration of uric acid in STZ-treated cells was about 3 fold that of control cells. This finding suggests that the reaction of xanthine oxidase is facilitated in the cells exposed to STZ probably due to an increased supply of substrate resulting from decrease in intracellular ATP. Based on these results, a possible mechanism of the effect of allopurinol on the cytotoxic effect of STZ via xanthine oxidase is discussed.

Adenosine Triphosphate↗
PubMed1990

Direct evidence for the presence of methylmercury bound in the thyroid and other organs obtained from mice given methylmercury; differentiation of free and bound methylmercuries in biological materials determined by volatility of methylmercury.

Peroxidase in mouse thyroid was inhibited by mercuric chloride but not by methylmercury in in vivo and in vitro systems (Nishida, et al., J. Histochem. Cytochem., 37, 723 (1989)). To identify the reason for the difference, the present study was conducted to examine whether methylmercury is indeed bound within cells or tissues. Mice were given radioactive methylmercury by intubation for 18 d and the tissues were dissected out and vacuum-dried. With this procedure, free methylmercury was evaporated off and the bound mercury remained. The thyroid, liver, kidney and fats examined showed no loss of radioactivity under the vacuum, indicating that the mercury was bound to the thyroid, as well as the other tissues. Radioactive mercuric chloride was nonvolatile regardless of the presence or absence of the tissues. The preferential affinity of methylmercury for SH-containing materials was re-confirmed by this method.

Animals↗