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Biomedical subjects

S Kawano

Publications and source records attributed to S Kawano.

At least 253 records · Page 14Linked to original sources
PubMed1994

[Reproductive and developmental toxicity studies of paclitaxel. (I)--Intravenous administration to rats prior to and in the early stages of pregnancy].

Paclitaxel, an antineoplastic agent, was administered intravenously to Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.1, 0.3 and 1.0 mg/kg for 63 days prior to mating and during the mating period in males, and for 14 days prior to mating and during the mating period as well as day 0 to day 7 of gestation in females. Results were as follows: 1. Body weight gains were shown a tendency to hasten in vehicle-treated male rats associated with the increased food consumption. However, the vehicle-treated group had no effect in the other parameters that were measured in this study when compared to the saline-treated group. 2. 1.0 mg/kg paclitaxel caused suppression of the body weight gains accompanied by the decreased food consumption in either male or female rats. 3. Adrenal and ovarian weights were decreased in 1.0 mg/kg dams at term. 4. The fertility indices in both sexes of 1.0 mg/kg were lower than the saline-treated group. However, the copulation indices in both sexes in 1.0 mg/kg rats were comparable to those of the saline-treated group. 5. Decreases in the number of corpora lutea, implantations and live fetuses or increases in the number of empty implantation sites and total embryo-fetal deaths were observed in 1.0 mg/kg dams. However, the fetal weights, crown-rump distances and tail lengths in live fetuses were not affected by paclitaxel treatment. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 0.3 mg/kg/day for parent animals and their fetuses.

Adrenal Glands↗
PubMed1994

[Reproductive and developmental toxicity studies of paclitaxel. (II)--Intravenous administration to rats during the fetal organogenesis].

Paclitaxel, an antineoplastic agent, was administered intravenously to pregnant Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.15, 0.3 and 0.6 mg/kg from day 7 to day 17 of gestation. Results were as follows: 1. The ossification of hyoid bodies was retarded in F1 fetuses by the vehicle. However, the vehicle-treated group had no effect in the other parameters that were measured in this study when compared to the saline-treated group. 2. Body weight gains and food consumption in F0 dams were not affected by paclitaxel during the gestation and lactation periods. 3. Paclitaxel failed to affect the organ weights in F0 dams. 4. Paclitaxel did not alter the prenatal development in F1 fetuses. 5. External, internal and skeletal malformations were not induced by paclitaxel. Further, paclitaxel did not affect the skeletal variations and ossification processes. 6. Paclitaxel did not alter the delivery status of F0 dams or viability and weaning indices in F1 pups. 7. The day required for presence of hair was significantly delayed in 0.6 mg/kg F1 pups at paclitaxel. However, the days required for pinnae detachment, incisor eruption, eye opening, testicular descent and vaginal opening were not affected by paclitaxel. 8. No effects on body weight gains or food consumption were observed in both male and female F1 rats. 9. Paclitaxel did not alter the developmental behavior, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 10. The reproductive performance in both male and female F1 rats were not affected by paclitaxel. 11. Paclitaxel did not alter the organ weights in both male and female F1 rats. 12. No influence on prenatal development was observed for F2 fetuses even at the highest dose level of paclitaxel. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 0.6 mg/kg/day and 0.3 mg/kg/day for dams (F0) and their offspring (F1), respectively.

Animals↗
PubMed1994

[Reproductive and developmental toxicity studies of paclitaxel. (III)--Intravenous administration to rats during the perinatal and lactation periods].

Paclitaxel, an antineoplastic agent, was administered intravenously to pregnant Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.1, 0.3 and 1.0 mg/kg from day 17 of gestation to postpartum day 21. Results were as follows: 1. The vehicle-treated group had no effect in any of the parameters that were measured in this study when compared to the saline-treated group. 2. 1.0 mg/kg paclitaxel caused suppression of the body weight gains associated with the decreased food consumption in F0 dams during the lactation period. 3. Thymic, heart and uterine weights were reduced in 1.0 mg/kg F0 dams at completion of the lactation period. In addition, thymic atrophy was observed for 1.0 mg/kg F0 dams macroscopically. 4. Paclitaxel did not alter the delivery status of F0 dams or birth, viability and weaning indices in F1 pups. 5. The days required for presence of hair, incisor eruption and testicular descent were statistically delayed in 1.0 mg/kg F1 rats. 6. The latency time for olfactory orientation was prolonged in 1.0 mg/kg F1 rats on postnatal day 15. Further, the positive response rates for air righting were reduced in 1.0 mg/kg F1 rats from postnatal day 17 to day 20. 7. 1.0 mg/kg paclitaxel caused suppression of the body weight gains in male F1 rats from postnatal week 1 to week 12. Though body weight gains were decreased in 1.0 mg/kg female F1 rats from postnatal week 1 to week 7, there were no significant differences between dosed animals and saline-treated animals regarding the body weight gains and food consumption during the gestation period. 8. Paclitaxel did not affect the learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 9. The reproductive performance in both male and female F1 rats were not affected by paclitaxel. 10. Splenic weights were reduced in 1.0 mg/kg male and female F1 rats at weaning. Furthermore, liver weights were decreased in 1.0 mg/kg male F1 rats after mating. 11. No influence on prenatal development was observed for F2 fetuses even at the highest dose level of paclitaxel. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 1.0 mg/kg/day and 0.3 mg/kg/day for dams (F0) and their offspring (F1), respectively.

Animals↗
PubMed1994

Adrenocortical response to tail-suspension in young and old rats.

We recently showed that increased glucocorticoid secretion aggravates disuse atrophy when induced by skeletal unloading. Disuse atrophy in the elderly is becoming a serious problem in many developed countries. In this study we attempted to examine how aging affects the glucocorticoid response to skeletal unloading. Three groups of rats (aged 5 weeks, 12 months and 18 months) were subjected to 7 days of hind limb unloading by tail-suspension. Urinary excretion of corticosterone over a 24-hr period were monitored every other day. Corticosterone excretion in the control group of 5-week-old rats was initially 87.4 +/- 12.8 ng/day and did not change throughout the experiment. Tail-suspension experiments yielded a significant increase (more than 3 fold) in excretion on days 1 and 3 of the suspension before returning to control levels. In the 12-month-old rats, a marked increase in the basal corticosterone level was observed in the control rats throughout the experiment, while the increase by tail-suspension was attenuated with a transient, significant increase on day 5. In 18-month-old rats, a further increase in the basal level was observed in the control group, although excretions tended to increase steadily from day 1 to day 3 and remained high until day 7. Urinary excretion of corticosterone among the 18-month-old suspension group was similar to those observed in the control group. These results indicate that the younger (5-week-old) rats adapted the stress load caused either by tail-suspension or manipulation alone faster than the older rats did (12 or 18 months old). The observation that basal corticosterone excretion increases with age suggests, alterations in the hypothalamic-pituitary-adrenal axis among the aged rats which might aggravates disuse atrophy induced by skeletal unloading.

Adaptation, Physiological↗
PubMed1994

Changes in serum 1,25-dihydroxyvitamin D3 and mRNAs for osteocalcin and alkaline phosphatase in femur unloaded by tail suspension in rats.

To elucidate the mechanism involved in the development of disuse atrophy of bone by skeletal unloading, changes in osteocalcin and alkaline phosphatase mRNAs, markers for bone formation, were studied in the hind limb bones of tail-suspended rats. Tail suspension for 8 and 14 days resulted in a significant decrease in osteocalcin mRNA in the femur when compared with age-matched non-suspended controls. Serum 1,25-dihydroxyvitamin D3 decreased to 60% of the control level after 8 days of skeletal unloading but regained almost normal levels over the next 7 days. Since it is known that vitamin D3 up regulates and glucocorticoid down regulates transcription of the osteocalcin gene, the endocrine response evoked by tail suspension may have aggravated the disuse atrophy caused by skeletal unloading in this study.

Alkaline Phosphatase↗
PubMed1994

Serum gamma-glutamyl transferase level in predicting hypertension among male drinkers.

In a 10 year prospective study, we investigated the utility of the level of serum gamma-glutamyl transferase (GGT), a biological marker of alcohol consumption, in predicting the development of hypertension in Japanese male drinkers, all of whom lived in a rural community. The study included 77 men, aged 30-69 years, who were normotensive (SBP < or = 140 mmHg and DBP < or = 90 mmHg) and who had no prior history of antihypertensive treatment at baseline (1979-80). Hypertension was defined as SBP of > 140 mmHg and/or DBP of > 90 mmHg and/or starting antihypertensive medication. The age-adjusted relative risk for subjects with a serum GGT level of 20 U/l or higher compared with those with a level of < 10 U/l was 4.18 (95% confidence interval, 1.59-11.01, P = 0.004). The relative risk remained significant after adjustment for baseline BP level and the amount of alcohol consumption. These results suggest that the serum GGT levels may predict the future development of hypertension among drinkers.

Adult↗
PubMed1994

Protective effect of ebselen on constrictive hepatic vasculature: prevention of alcohol-induced effects on portal pressure in perfused livers.

The effect of an organoselenium compound, ebselen [2-phenyl-1,2-benzisoselenazol-3-(2H)-one], on ethanol-induced liver damage through perturbation of microcirculation was investigated in perfused livers from fed rats. Infusion of ethanol at concentrations > or = 25 mM into the portal vein increased portal pressure in a concentration-dependent manner. Release of lactate dehydrogenase (LDH) into the effluent perfusate was minimal at 30 min; thereafter LDH release began to increase gradually until the end of the experiment (60 min after the onset of ethanol infusion) and was dependent on ethanol concentration. Simultaneous infusion of ebselen at a concentration of 10 or 30 microM with ethanol reduced significantly this ethanol-induced increase in portal pressure by 50 to 75% (P < .05) and LDH release by 70% (P < .05). When endothelin-1 or phenylephrine was infused into the liver, portal pressure was increased, reaching maximal levels (50 +/- 17 and 46 +/- 7 mm of H2O, respectively) and then decreasing gradually. Ebselen reduced the maximal increase in portal pressure induced by endothelin-1 (18 +/- 2 mm of H2O) by 64% (P < .05). In addition, ebselen decreased the maximal levels of portal pressure induced by phenylephrine (8 +/- 1 mm of H2O) by 83% (P < .05). These data indicate that ebselen has a vasodilative effect on constriction of hepatic vasculature and diminishes ethanol-induced hepatic damage by offsetting ethanol-induced increase in portal pressure. Thus, ebselen may prove useful for treatment of alcoholic liver injury via improvement of microcirculatory disturbances.

Animals↗
PubMed1994

[Clinical effects and safety of granisetron administration against CDDP chemotherapy in lung cancer. Lung Cancer Study Group].

Granisetron (3 mg/body) was administered immediately before single CDDP administration (80 mg/m2 or more) to 53 patients with lung cancer. This chemotherapy was performed a total of 73 times. Concerning Grade 2 or 3 nausea and vomiting, good conditions were observed on day 1 (day of treatment), most marked aggravation on day 2, and initiation of improvement on day 4. Vomiting was slight on day 1, most aggravated on day 2, but began to improve on day 3; good results were generally observed thereafter. Decreased appetite was slight on day 1, but was most aggravated on day 3 and 4; its recovery was delayed even until day 7. In the treatment for delayed emesis, comparison was made among the group treated with granisetron alone who did not require treatment for delayed emesis, the group with delayed emesis treated with granisetron, and the group with delayed emesis treated with drugs other than granisetron. Slightly better results were observed in terms of nausea, vomiting, and the frequency of vomiting in the group treated with granisetron alone on days 2 and 3. However, no significant difference was observed in decreased appetite among the 3 groups. Granisetron had no side effects and was safe. It inhibited vomiting, but measures to improve decreased appetite are needed.

Adult↗
PubMed1994

Behavior of mitochondria, chloroplasts and their nuclei during the mitotic cycle in the ultramicroalga Cyanidioschyzon merolae.

The behavior of cell nuclei, mitochondria and chloroplasts was followed during the mitotic cycle in the primitive unicellular red alga Cyanidioschyzon merolae by epifluorescence microscopy after staining with 4',6-diamidino-2-phenylindole (DAPI) or 3,3'-dihexyloxacarbocyanine iodide (DIOC6), by fluorimetry using a video-intensified microscope photon-counting system (VIMPCS), and by electron microscopy. The cells were classified into five types based on differences in the shape, size, and distribution of organelles in each cell: type I, II, III, IV, and V. Types II, III, IV, and V appear in that order concomitant with a decrease in type I after the cells are subjected to darkness during synchronous culture, suggesting that the organelles divide in the following sequence: chloroplast, mitochondrion, and cell nucleus. The mitochondrial DNA (mt-DNA) and the chloroplast DNA (cp-DNA) are synthesized during stage I, while the cell-nuclear DNA (cn-DNA) is duplicated in stage II. The mitochondria- and chloroplast-nuclear divisions are completed in stage IV. The mitochondrial and chloroplast divisions begin simultaneously in stage II, and chloroplast division finishes just prior to mitochondrial division. The end result is that C. merolae multiplies by binary fission. Electron microscopic examination of serial thin sections of the chloroplast clearly show that the chloroplasts in types II and III are divided by a chloroplast dividing ring (CD-ring), which is located on the cytoplasmic side of the outer envelope at the equatorial region between the daughter chloroplasts. The CD-ring may be involved in chloroplast division throughout the plant kingdom in primitive unicellular algae and higher plants.

Cell Nucleus↗
PubMed1994

Role of nitric oxide in ethanol-induced perturbation of hepatic microcirculation in rat liver.

Microcirculatory disturbance is one of the main pathogenetic features of alcoholic liver damage. We have demonstrated that ethanol increased portal pressure, leading to hepatic hypoxia and hepatocellular necrosis. In this ethanol-induced hepatic vasoconstriction, nitric oxide, an endothelial derived relaxing factor, dilated constrictive hepatic vasculature and reduced liver injury by improving the microcirculatory disturbance.

Animals↗
PubMed1994

Alcohol and endogenous nitric oxide in hepatic microcirculation.

This study investigated the role of endogenous nitric oxide in the regulation of hepatic vascular tone in the presence of ethanol. In the perfused rat liver, upon the initiation of ethanol infusion into the liver, portal pressure was increased in a dose-dependent manner, reaching maximal levels in 2-5 min, then decreasing gradually. Simultaneous infusion of N(G)-monomethy 1-L-arginine, a nitric oxide synthesis inhibitor, enhanced this ethanol-induced increase in portal pressure. This enhancement was reversed by simultaneous infusion of a precursor of nitric oxide, L-arginine. These results suggest that endogenous nitric oxide acts as a vasodilator which reduces ethanol-induced vasoconstriction, thus improving the perturbation of hepatic microcirculation by ethanol.

Animals↗
PubMed1993

Human recombination activating gene-1 in leukemia/lymphoma cells: expression depends on stage of lymphoid differentiation defined by phenotype and genotype.

The recombination activating gene, RAG-1, which is supposed to encode a molecule regulating V(D)J recombination, has been isolated. In the current study, the distribution of RAG-1 expression in human neoplastic hematopoietic cells was compared with the phenotypic and genotypic status of differentiation. Thirty-one hematopoietic cell lines (16 B-lineage, 9 T-lineage, 2 Hodgkin's disease, and 4 nonlymphoid cell lines) were investigated for the expression of human RAG-1 using the reverse-transcriptase polymerase chain reaction (RT-PCR). RAG-1 was not expressed in nonlymphoid, Hodgkin's disease, or mature-stage lymphoid cell lines, but was present in some acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) cell lines. The investigation was extended to 45 cases of fresh ALL/LBL cells. The patterns of RAG-1 expression found in the cell lines and fresh ALL/LBL cells were similar. In B-lineage cells, the product of RAG-1 RT-PCR was detected in CD19+ CD10- CD20- CD5- stage (stage II, Nadler's classification) and was at the highest level in CD19+ CD10+ CD20- CD5- stage (stage III), but was absent or limited in CD19+ CD10+ CD20-+ CD5- (stage IV) or CD19+ CD10+ (or CD10-) CD5+. In stage II, monoclonal gene rearrangements of only the immunoglobulin heavy chain (IgH) were found, whereas monoclonal gene rearrangements of both IgH and T-cell receptor (TCR)-beta chain were frequently noted in stages III and IV. The expression of CD20 or CD5 antigen apparently correlated with the decline of RAG-1 expression. In T-lineage cells, RAG-1 was highly expressed in CD3- CD4+ CD8+/CD3+ CD4+ CD8+ thymic stages, but was negative or only weakly expressed in the CD3- CD4- CD8- prothymic or early thymic stage, in which the TCR-beta gene was often germline, or the CD3+ CD4+ CD8- mature thymic stage. The relative levels of RAG-1 mRNA give an additional delineating frame to the schemes of lymphoid differentiation based on phenotypic and genotypic status. RAG-1 is exhibited by cells of the thymic stage capable of synthesizing TCR or expressing it on the cell surface. The weak or absent expression of RAG-1 in the prothymic or early thymic stage suggests that the contribution of RAG-1 to the gene rearrangement may differ quantitatively between TCR-delta/TCR-gamma and TCR-beta.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗
PubMed1993

Isolation and characterization of novel genes which are expressed during the very early stage of zygote formation in Chlamydomonas reinhardtii.

We have obtained five cDNA clones which are complementary to transcripts that accumulate specifically during the early stage of zygote formation in Chlamydomonas reinhardtii. Based on the time-course of transcript accumulation of their corresponding genes, these clones were classified into two groups: an early expression group (three clones; pZS102-1, pZS102-69, pZS1802) and a late expression group (two clones; pZS1860 and pZS1886). The levels of transcripts in the former group reached a maximum 30 min after the onset of mating, whereas those in the latter group peaked at 3 h. The addition of 10 micrograms/ml of cycloheximide reduced the decline in the levels of transcripts, except in the transcript corresponding to pZS102-69. Two clones, pZS102-1 and pZS102-69, contained highly-homologous predicted open-reading frames, and were judged to be cDNAs for two members of a novel gene family. These genes were referred to as zys1A and zys1B, respectively.

Amino Acid Sequence↗
PubMed1993

Cell kinetics of mucosal atrophy in rat stomach induced by long-term administration of ammonia.

BACKGROUND: Helicobacter pylori produces ammonia in the stomach from urea. The present study was undertaken to clarify whether ammonia has an etiological role in H. pylori-associated gastric mucosal atrophy. METHODS: Ammonia at 0.01% was administered as drinking water for 8 weeks and mucosal cell migration rate and cell proliferation were investigated in rat stomach. RESULTS: Long-term administration of 0.01% ammonia for 4-8 weeks decreased mucosal thickness in the antrum but not in the body. Acceleration of cell migration preceded the occurrence of mucosal atrophy. Labeling indices in both antral and body mucosa significantly increased in all ammonia-treated groups, compared with those of the control group. In the antrum, the proliferative zone was significantly enlarged as mucosal atrophy developed, whereas, in body mucosa, enlargement of the proliferative zone occurred despite the absence of mucosal atrophy. CONCLUSION: Ammonia at 0.01% accelerates epithelial migration, especially in the antrum, leading to mucosal atrophy. Acceleration of epithelial proliferation occurs during the development of mucosal atrophy.

Ammonia↗
PubMed1993

Lateral preoptic neurons inhibit thirst in the rat.

Kainic acid (KA) and muscimol were injected into the lateral preoptic area (LPO) of the rat to study their effects on drinking behavior. A low dose (5 ng) of KA, which stimulates neurons, decreased the amount of water intake induced by hypertonic saline (IP) and angiotensin II (SC). Injection of 2 ng muscimol, a potent GABAA receptor agonist that suppresses neurons, facilitated drinking responses induced by hypertonic saline, but did not affect angiotensin II-induced drinking. Rats injected with a high dose (150 ng) of KA, which destroys neurons, showed marked polydipsia accompanied by increased urination. One week after the KA lesion, drinking and urine output recovered to normal. During the polydipsia, a small volume of concentrated urine could be excreted if water intake was restricted. After recovery, excessive drinking responses followed water deprivation and hypertonic saline load. The rats normally drank water in response to angiotensin II and to polyethylene glycol solution. The results show that activation of LPO neurons inhibits water intake, and that suppression of LPO neurons facilitates osmotically induced water intake. Therefore, LPO neurons are probably involved in the inhibition of thirst.

Animals↗