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S Kamimura

Publications and source records attributed to S Kamimura.

At least 55 records · Page 3Linked to original sources

Cytokine gene expression by Kupffer cells in experimental alcoholic liver disease.

Kupffer cell-derived cytokines are believed to play pivotal paracrine roles in the pathogenesis of alcoholic liver disease (ALD). To evaluate this hypothesis, Kupffer cell gene expression of tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-6, and transforming growth factor-beta 1 (TGF beta 1) were directly examined in the rat model of ALD. Kupffer cells were isolated from the model after 10 and 17 weeks of intragastric ethanol infusion. These two durations resulted in focal hepatocellular injury and liver fibrogenesis, respectively. Oxidative stress as assessed by the hepatic level of thiobarbituric acid reacting substances, was evident at 10 weeks but more pronounced at 17 weeks. The steady state messenger RNA (mRNA) levels of the cytokines were examined by Northern blot analysis using RNA samples from freshly isolated Kupffer cells, and the release of the cytokines was quantitated ex vivo using a 3-day culture. The mRNA levels of TNF alpha and TGF beta 1 were significantly increased by 183% and 204% at 10 weeks and 231% and 295% at 17 weeks in the ethanol-fed rats, respectively. Ex vivo release of TNF activity by control Kupffer cells was undetectable or very low (< 2U/10(5) cells/18 hours) at both time points, but the cells from the ethanol-fed animals secreted appreciably more TNF (27.8 +/- 7.6 U at 10 weeks and 40.4 +/- 10.3 U at 17 weeks). The release of the latent TGF beta 1 protein was also coordinately increased by 143% at 10 weeks and 238% at 17 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Nanometer scale vibration in mutant axonemes of Chlamydomonas.

Flagellar axonemes of sea urchin sperm display high frequency (200-400 Hz) vibration with nanometer scale amplitudes in the presence of ATP [Kamimura and Kamiya, 1992: J. Cell Biol. 116:1443-1454]. To investigate how various axonemal components affect the vibration, we examined vibration in wild-type and mutant axonemes of Chlamydomonas. At 1 mM ATP, wild-type axonemes underwent vibration at 100-650 Hz with amplitudes of 4-40 nm. This vibration was similar to, but less regular than, that in sea urchin sperm. Axonemes of the mutants ida1 and ida4 lacking part of the inner arm dynein underwent vibrations indistinguishable from that of wild-type. The mutant oda1 lacking the entire outer arm underwent vibration at about half the wild-type frequency. Unexpectedly, the paralyzed mutants pf18 lacking the central pair and pf14 lacking the radial spokes displayed vibration with significantly higher frequencies and smaller amplitudes than those in the wild-type vibration. These results indicate that the high-frequency vibration is common to many kinds of mutant axonemes that lack various axonemal substructures, but that its manner is sensitive to the presence of outer arm dynein and the central pair/radial spoke system. Simultaneous measurements of amplitude and frequency in wild-type and mutant axonemes suggest that the velocity of microtubule sliding in vibrating axonemes is lower than the velocity of sliding under load-free conditions. The velocity is particularly low in pf18.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A Globosus amorphus from an in vitro fertilized embryo transferred to a Japanese black cow.

A Globosus amorphus along with a living calf was encountered following the transfer of blastocysts obtained by in vitro fertilization of in vitro-matured follicular oocytes in Japanese black cattle. Two embryos obtained 9 days after in vitro fertilization developed into either a hatched blastocyst with distinct inner cell mass or an expanded blastocyst with indistinct inner cell mass. The embryos were loaded into a 0.25-ml plastic straw and were nonsurgically transferred to the uterus of a heifer on Day 8 (Day 0 = estrus). On Day 75, a twin pregnancy was ultrasonically diagnosed in the right uterine horn, in which a live fetus with distinct limbs and a concomitant ovoid mass were detected. On Day 287, the dam developed parturient paralysis with dropsy of the fetal membranes. By palpation per rectum an ovoid mass was detected in the body of the uterus [corpus uteri] and a larger live fetus was in the uterine horn. A cesarean section was performed to extract a live fetus and a Globosus amorphus. The live fetus was female with the 60, XX female complements.

Journal Article↗

Differential catabolism of 22-oxacalcitriol and 1,25-dihydroxyvitamin D3 by normal human peripheral monocytes.

22-Oxacalcitriol [1,25-(OH)2-22oxa-D3] mimics the action of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in a variety of target tissues, including the systemic control of calcitriol metabolism. Similar to 1,25-(OH)2D3, 1,25-(OH)2-22oxa-D3 decreases the rate of 1,25-(OH)2D3 synthesis and accelerates its metabolic clearance rate. We have previously shown that in normal human monocytes, physiological concentrations of 1,25-(OH)2D3 and 1,25-(OH)2-22oxa-D3 determine identical suppression of 1,25-(OH)2D3 synthesis. Moreover, both sterols have a similar potency to induce vitamin D degradation through stimulation of the C24-hydroxylation pathway. In this study, we examined the ability of normal human monocytes to metabolize 1,25-(OH)2-22oxa-D3 and whether the enzymes involved are the same as those that catabolize 1,25-(OH)2D3. Time-course experiments demonstrated no detectable basal catabolic activity. However, exogenous 1,25-(OH)2D3 at physiological concentrations induced 1,25-(OH)2-22oxa-D3 degradation by normal human monocytes. Competition experiments showed that a 10-fold molar excess of unlabeled 1,25-(OH)2D3 inhibited tritiated-1,25-(OH)2-22oxa-D3 catabolism by 85%, whereas a 10-fold excess of unlabeled 1,25-(OH)2-22oxa-D3 reduced tritiated-1,25-(OH)2-22oxa-D3 catabolism by 33%. In contrast, although a 10-fold excess of unlabeled 1,25-(OH)2D3 reduced tritiated 1,25-(OH)2D3 catabolism by 60%, a 1000-fold excess of 1,25-(OH)2-22oxa-D3 was required to reduce tritiated 1,25-(OH)2D3 catabolism to this degree. The apparent Km for 1,25-(OH)2-22oxa-D3 was significantly higher than that of 1,25-(OH)2D3 (2.0 +/- 0.8 0.9 +/- 0.2 nM, respectively; P < 0.001) for the catabolic pathway induced by physiological concentrations of 1,25-(OH)2D3. Moreover, the presence of 0.65 nM 1,25-(OH)2D3 caused an additional increase in the Km for 1,25-(OH)2-22oxa-D3 (3.2 +/- 0.8 nM). These data suggest that 1,25-(OH)2-22oxa-D3 may be less accessible than 1,25-(OH)2D3 to the hydroxylases involved in vitamin D catabolism. The resulting prolonged biological half-life of the analog in certain target tissues may be involved in its selectivity.

Binding, Competitive↗

Monitoring bovine embryo viability with early pregnancy factor.

The viability of the bovine embryo was monitored by measuring the early pregnancy factor (EPF). The EPF activity was measured by the rosette inhibition test before and after artificial insemination (AI) at natural estrus (n = 14), and after superovulatory treatment followed by embryo removal on day 7 after AI (n = 5). In the cows inseminated artificially at natural estrus, there were significant differences (p < 0.01) in the rosette inhibition titer (RIT) between pregnant and non-pregnant cows on day 13-16 and day 20-25 after AI. In the 8 pregnant cows, the RIT remained more than 5 from day 6-9 after AI. In the 6 non-pregnant cows, two patterns were observed. In one pattern, RIT rose transiently to more than 5 and decreased to less than 4 thereafter. In the other pattern, RIT remained less than 4 throughout the experimental period. The former pattern suggested early embryonic death, while the latter suggested that fertilization had not taken place or that early embryonic death had occurred before the first blood collection on day 6-9 after AI. In the cows superovulated followed by embryo removal on day 7 after AI, the RIT values were all less than 4 on the day of AI (day 0), rose to more than 5 on day 3 and thereafter then until the day of embryo removal on day 7. In 4 cows, the RIT decreased to less than 4 by 3 days after embryo removal, and in the remaining one cow, the RIT decreased to less than 4 by 7 days after embryo removal. These findings suggest that the measurement of EPF activity is useful for monitoring the viability of bovine embryos.

Animals↗

Postpartum resumption of ovarian activity and uterine involution monitored by ultrasonography in Holstein cows.

Postpartum resumption of ovarian activity in 40 Holstein cows was monitored by ultrasonography twice weekly until artificial insemination. The accuracy of ultrasonography for assessments of ovarian structures was examined by comparing results of in vivo ultrasonography with macroscopic findings of the same ovaries after slaughter. Correlation coefficients were 0.71 and 0.85 for number of follicles 10-14 mm and > or = 15 mm, and 0.99 for diameters of the largest follicle. Follicular profiles prior to first ovulation were characterized by single dominant follicle (DF > or = 10 mm) in 25 cows, two in 10, three in 4, and four in one, respectively. However, after first ovulation, two waves of DF prevailed. The total number of DF (7.2) or time of ovulation (3.6) before conception was positively correlated with postpartum intervals to conception (74.0 days). Profiles of the volume of corpus luteum estimated by ultrasonography paralleled with the variations of plasma progesterone levels. The volume of corpus luteum and the peak progesterone level were smaller after the first ovulation as compared with after the second or third ovulations. In the ultrasound images of uterus, two elliptical lines indicated cross section of endometrium and stratum vascularis. Uterine involution assessed by reaching the nadir of endometrium was completed by 41.5 days postpartum. Results indicated that the number of DF before the first ovulation and the volume of corpus luteum after the ovulation were smaller compared with those of the second and third ovulations.

Animals↗

Immunohistochemical demonstration of ethanol-inducible P450 2E1 in rat brain.

The microsomal ethanol-oxidizing system (MEOS) is a P450-dependent pathway for ethanol oxidation in hepatic microsomes. The bulk of MEOS activity is catalyzed by P450 2E1 (an ethanol-inducible isozyme of P450) in animal livers treated with ethanol. Rat brains also metabolize certain drugs, and it is theorized that a mechanism for drug metabolism exists within the brain which acts on P450. We compared immunohistochemical localization of P450 2E1 between ethanol-treated rats and pair-fed control rats. In control rats, immunoreactive P450 2E1 was detected in minute amounts in both basal ganglia and cerebellar cortices. After ethanol treatment, the content of P450 2E1 increased in the basal ganglia, and the enzyme was also induced in the cerebellar cortices, substantia nigra and hippocampus. We speculate that the rat brain metabolizes ethanol by P450 2E1.

Alcoholism↗

Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: association of lipid peroxidation with liver fibrogenesis.

The precise role of lipid peroxidation in the pathogenesis of alcoholic liver disease is still being debated. To explore the issue, this study was undertaken to investigate the status of lipid peroxidation, antioxidants and prooxidants at two discrete stages of experimental alcoholic liver disease. Male Wistar rats were intragastrically fed a high-fat diet plus ethanol for 5 or 16 wk (the duration that resulted in initiation of centrilobular liver necrosis or liver fibrosis, respectively). Lipid peroxidation was assessed in isolated microsomes and mitochondria with three parameters: malondialdehyde equivalents as determined by thiobarbituric acid assay, conjugated diene formation and 4-hydroxynonenal as a 2,4-dinitrophenylhydrazone derivative. To assess antioxidant systems, hepatic concentrations of glutathione, methionine and alpha-tocopherol were determined. The concentration of nonheme iron, a known prooxidant, was also measured. At wk 5, centrilobular liver necrosis was already evident in the ethanol-fed animals, with two- or threefold increases in plasma AST and ALT levels. At this stage, neither malondialdehyde equivalents nor conjugated diene values were elevated, and the 4-hydroxynonemal level was below 0.2 nmol/mg protein. Hepatic concentrations of methionine and alpha-tocopherol in these animals were increased two- and threefold, respectively, whereas the reduced glutathione level remained unchanged. When alcoholic liver disease had progressed to perivenular or bridging fibrosis at wk 16, all three parameters of lipid peroxidation showed consistent increases that were accompanied by significant reductions in the hepatic glutathione and methionine levels. Interestingly, the control animals pair-fed with the high-fat diet also had significantly elevated 4-hydroxynonenal levels at wk 16 compared to the wk 5 level.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes↗

Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron-dependent microsomal lipid peroxidation.

This study investigated the role of cytochrome P-450 2E1 in enhanced microsomal lipid peroxidation in experimental alcoholic liver disease. We also examined the contribution of this isoform to the increased microsomal injury in alcoholic liver disease caused by carbon tetrachloride-induced or iron-induced oxidant stress. Adult male Wistar rats were intragastrically infused with a high-fat diet and ethanol or glucose for 16 wk; this resulted in hepatic lipid peroxidation and fibrogenesis in the ethanol-fed animals. Microsomes were isolated by differential centrifugation in the presence of 100 mumol/L deferoxamine, washed twice in buffer without deferoxamine and incubated in the absence or presence of ethanol (50 mmol/L), carbon tetrachloride (150 mumol/L), ferric citrate (50 mumol/L) or ferric citrate plus ethanol at 37 degrees C for 30 min in an NADPH-generating system. The basal rate of lipid peroxidation in microsomes isolated from ethanol-fed rats was increased by 52% compared with that in microsomes from controls. Carbon tetrachloride-induced and ferric citrate-induced lipid peroxidation were also accentuated in microsomes from ethanol-fed rats, by 76% and 108%, respectively. Ethanol added in vitro significantly reduced basal (-58%) and ferric citrate-induced (-48%) lipid peroxidation in microsomes from ethanol-fed rats, whereas it had an insignificant effect on that in control microsomes. In fact, this protective effect of ethanol on microsomes from ethanol-fed rats resulted in attenuation of the difference in the level of microsomal lipid peroxidation between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hepatic mitochondrial glutathione depletion and progression of experimental alcoholic liver disease in rats.

Long-term ethanol feeding has been shown to selectively reduce hepatic mitochondrial glutathione content by impairing mitochondrial uptake of this thiol. In this study, we assessed the role of this defect in evolution of alcoholic liver disease by examining the mitochondrial glutathione pool and lipid peroxidation during progression of experimental alcoholic liver disease to centrilobular liver necrosis and fibrosis. Male Wistar rats were intragastrically infused with a high-fat diet plus ethanol for 3, 6 or 16 wk (the duration that resulted in induction of liver steatosis, necrosis and fibrosis, respectively). During this feeding period, the cytosolic pool of glutathione remained unchanged in the ethanol-fed animals compared with that in pair-fed controls. In contrast, the mitochondrial pool of glutathione selectively and progressively decreased in rats infused with ethanol for 3, 6 or 16 wk, by 39%, 61% and 85%, respectively. Renal mitochondrial glutathione level remained unaffected throughout the experiment. Serum ALT levels increased significantly in the ethanol-fed rats at 6 wk and remained elevated at 16 wk. In the mitochondria with severely depleted glutathione levels at 16 wk, enhanced lipid peroxidation was evidenced by increased malondialdehyde levels. Thus a progressive and selective depletion of mitochondrial glutathione is demonstrated in the liver in this experimental model of alcoholic liver disease and associated with mitochondrial lipid peroxidation and progression of liver damage.

Alanine Transaminase↗

High-frequency vibration in flagellar axonemes with amplitudes reflecting the size of tubulin.

Flagellar axonemes of sea urchin sperm display high-frequency (approximately 300 Hz) vibration with nanometer-scale amplitudes in the presence of ATP (Kamimura, S., and R. Kamiya. 1989. Nature (Lond.). 340:476-478). The vibration appears to represent normal mechanochemical interaction between dynein and microtubules because the dependence of the frequency on MgATP concentration is similar to that of the axonemal motility, and because it is inhibited by micromolar concentrations of vanadate. In this study a two-dimensional photo-sensor was used to characterize this phenomenon in detail. Several new features were revealed. First, the vibration was found to be due to a back-and-forth movement of the doublet microtubules along the axonemal length. Two beads attached to different parts of the same axoneme vibrated in unison, i.e., synchronized exactly in phase. This suggested that the outer doublet can be regarded as a stiff rod in vibrating axonemes. Second, evidence was obtained that the amplitude of the vibration reflected the number of active dynein arms. Third, under certain conditions, the vibration amplitude took stepwise values of 8 x N + 4 nm (N = 0, 1, 2, 3, or 4), indicating that the amplitude of microtubule sliding was limited by the size of tubulin dimer (8 nm) or monomer (4 nm). To explain this phenomenon, a model is presented based on an assumption that the force production by dynein is turned off when dynein is subjected to tensile force; i.e., dynein is assumed to be equipped with a feedback mechanism necessary for oscillation.

Adenosine Triphosphate↗

Tubulin protofilaments and kinesin-dependent motility.

Microtubules are built of tubulin subunits assembled into hollow cylinders which consist of parallel protofilaments. Thus, motor molecules interacting with a microtubule could do so either with one or several tubulin subunits. This makes it difficult to determine the structural requirements for the interaction. One way to approach the problem is to alter the surface lattice. This can be done in several ways. Proto-filaments can be exposed on their inside (C-tubules or "sheets"), they can be made antiparallel (zinc sheets), or they can be rolled up (duplex tubules). We have exploited this polymorphism to study how the motor protein kinesin attached to a glass surface interacts and moves the various tubulin assemblies. Microtubules glide over the surface along straight paths and with uniform velocities. In the case of C-tubules, approximately 40% glide similarly to microtubules, but a major fraction do not glide at all. This indicates (a) that a full cylindrical closure is not necessary for movement, and (b) that the inside surface of microtubules does not support gliding. With zinc sheets, up to 70% of the polymers move, but the movement is discontinuous, has a reduced speed, and follows along a curved path. Since zinc sheets have protofilaments alternating in orientation and polarity, this result suggests that in principle a single protofilament can produce movement, even when its neighbors cannot. Duplex microtubules do not move because they are covered with protofilaments coiled inside out, thus preventing the interaction with kinesin. The data can be explained by assuming that the outside of one protofilament represents the minimal track for kinesin, but smooth gliding requires several parallel protofilaments. Finally, we followed the motion of kinesin-coated microbeads on sea-urchin sperm flagella, from the flagellar outer doublet microtubules to the singlet microtubule tips extending from the A-tubules. No change in behavior was detected during the transition. This indicates that even if these microtubules differ in surface lattice, this does not affect the motility.

Animals↗

Long duration of erythrocyte hypoplasia after bone marrow transplantation.

Bone marrow transplantation was performed on a 15 year old girl with chronic myelogenous leukemia. The bone marrow was obtained from her younger sister, who was human leukocyte antigen haplo-identical but major ABO incompatible. As a result, the condition of pure red cell aplasia (PRCA) persisted over a long period of time. In order to overcome major ABO incompatibility, erythrocytes were eliminated from the bone marrow graft before transplantation, and methotrexate and cyclosporine (CsA) were used to prevent graft-versus-host disease (GVHD). Administration of erythropoietin proved ineffective. B19 parvovirus infection could not be detected during that time. Agglutinin titers decreased to less than fourfold in parallel with the recovery of erythrocytes. Reports on similar PRCA have been limited to cases of transplantation with ABO incompatibility and cases where CsA was administered to prevent GVHD. This suggests that ABO incompatibility and CsA might be related to the development of PRCA.

ABO Blood-Group System↗

The effect of 22-oxacalcitriol on serum calcitriol.

1,25-Dihydroxyvitamin D3 (1,25D) regulates its own levels in circulation by affecting its rates of synthesis and degradation, 22-Oxacalcitriol (OCT), a vitamin D analog with low calcemic activity, decreases circulating PTH levels, one of the regulators of renal 1 alpha-hydroxylase, and stimulates vitamin D degradation in vitro. The purpose of this study was to examine the effects of OCT administration on serum levels of 1,25D. In normal rats, OCT administration (4-200 ng, ip, daily for 5 days) caused a dose-dependent reduction in serum calcitriol levels. At a dose of 200 ng, OCT reduced serum 1,25D from 34.5 +/- 2.7 to 10.9 +/- 0.7 pg/ml (P less than or equal to 0.01) without significant changes in ionized Ca or phosphorus levels. The contribution of the suppression of PTH by OCT to the reduction of serum 1,25D was examined by administering OCT to parathyroidectomized (PTX) rats. Two hundred nanograms of OCT, ip, daily for 5 days significantly reduced serum calcitriol from 29.7 +/- 7.6 to 9.1 +/- 0.5 pg/ml (P less than or equal to 0.01) in rats fed a normal calcium diet. Because OCT increased total calcium (TCa) in this group from 7.4 +/- 0.1 to 9.5 +/- 0.3 mg/dl, similar doses of OCT were given to PTX rats fed a calcium-deficient diet. OCT decreased 1,25D from 58.9 +/- 8.9 to 10.3 +/- 0.4 pg/ml and increased TCa from 4.8 +/- 0.2 to 7.4 +/- 0.1 mg/dl. Comparison of serum 1,25D for identical TCa levels in PTX rats (normal calcium diet controls vs. calcium-deficient diet, OCT-treated) clearly indicates that OCT per se reduced serum 1,25D. Further support for a direct effect of OCT was provided by studies in PTX rats fed a low phosphorus diet. OCT decreased serum 1,25D from 125.8 +/- 15.6 to 10.9 +/- 0.6 pg/ml without significant changes in TCa. To further characterize the mechanisms involved in this effect, similar studies were performed in six normal dogs. Intravenous administration of 0.75 micrograms OCT every other day for 1 week decreased serum calcitriol from 25.4 +/- 3.2 to 12.2 +/- 1.3 pg/ml (P less than or equal to 0.002). Ionized Ca and phosphorus remained unchanged. Despite the short half-life of OCT in the circulation, 1,25D levels returned to basal concentrations 96 h after the last dose of OCT.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Changes in plasma human atrial natriuretic peptide (hANP) level in normal pregnancy and pregnancy induced hypertension.

We determined plasma human atrial natriuretic peptide (hANP) levels in normal pregnancy and pregnancy induced hypertension (PIH). The plasma hANP levels slightly decreased in the first trimester of normal pregnancy and tended to recover as pregnancy advanced, although these changes were slight. However, the plasma hANP level in puerperium was higher than that in the third trimester of normal pregnancy. The plasma hANP level in mild PIH was not significantly higher than that in the third trimester of normal pregnancy. In contrast, the plasma hANP level in three cases of severe PIH was approximately 200% higher than those in the normal third trimester and mild PIH.

Atrial Natriuretic Factor↗

[Tryptophan and its metabolite concentrations in human plasma during the perinatal period].

The concentration of tryptophan (free and protein bound) and its metabolites in the plasma of the maternal vein and in the umbilical vein, umbilical artery and neonatal vein were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in the umbilical vein and artery were significantly higher than those in the maternal vein. Especially the 3-OHAA level in umbilical blood was approximately 50 times as high as that in maternal blood. The concentration of total tryptophan in the plasma of the neonatal vein showed a marked decrease at one day after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in the plasma of the neonatal vein. In the blood, ratios of free to total tryptophan and kynurenine were kept at a constant level throughout the perinatal period. In conclusion, the present study suggests that tryptophan metabolism may play an important role in fetal development.

Chromatography, High Pressure Liquid↗

Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period.

Concentrations of tryptophan (free and protein bound) and its metabolites in plasma of maternal vein at delivery, umbilical vein, umbilical artery, neonatal vein and breast milk were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in umbilical vein and artery were significantly higher than those in maternal vein. The concentration of total tryptophan in plasma of neonatal vein showed marked decrease at 24 h after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in plasma of neonatal vein. The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. In the blood, ratios of free to total of tryptophan and kynurenine were kept at constant level throughout the perinatal period.

Chromatography, High Pressure Liquid↗