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Biomedical subjects

K Kawashima

Publications and source records attributed to K Kawashima.

At least 163 records · Page 9Linked to original sources
PubMed1996

An anatomic study of the latissimus dorsi-rib flap: an extension of the subscapular combined flap.

The anatomy of the vascular perforators between the latissimus branch of the thoracodorsal vessels and the lateral branch of the dorsal rami of the intercostal vessels was studied in a series of 10 dissections in 5 preserved cadavers to develop the latissimus dorsi myocutaneous flap combined with a vascularized rib. The distances between the communicating perforators and the spinous process and the iliac crest, which become a good guide for design of the rib flap, were measured. An extension of the combined flap including the scapular osteocutaneous flap, latissimus dorsi myocutaneous flap, and vascularized eleventh and twelfth ribs that is nourished by a "single" subscapular vascular system was demonstrated. This technique, which provides a large amount of skin, muscle, and bone, is very effective for reconstruction of an extended composite maxillary and mandibular defect.

Aged↗
PubMed1996

Failure to detect mutations in the retinoblastoma protein-binding domain of the transcription factor E2F-1 in human cancers.

The functions of the transcription factor E2F-1 are regulated by the RB protein through the RB-binding domain of E2F-1 and this factor is considered to be an important molecule that functions downstream of the RB protein. In order to determine whether E2F-1 that cannot bind to RB might be associated with various human cancers, we searched for mutations in the RB-binding domain of E2F-1 using samples of DNA from various clinical specimens obtained from 406 cancer patients (with lung, pancreatic, stomach, colon, esophageal, and hepatic cancers) by analysis of polymerase chain reaction-mediated single-strand conformational polymorphism. No mutations or deletions were detected in genes for E2F-1 from any of the tumor tissues examined. These results suggest that a mutation or deletion in E2F-1 that might affect binding of the RB protein is not involved in human cancers.

Base Sequence↗
PubMed1996

Determination of acetylcholine concentration in cerebrospinal fluid of patients with neurologic diseases.

INTRODUCTION: Acetylcholine (ACh) is a well known neurotransmitter in the central nervous system, but determining its level in cerebrospinal fluid (CSF) is very difficult and the origin of CSF ACh is still unknown. In this study, we attempted to measure CSF ACh by a specific and sensitive radioimmunoassay (RIA) from patients with neurologic diseases. MATERIAL AND METHODS: Patients with cerebral infarction (n = 7), Parkinson's disease (n = 6), spinocerebellar degeneration (n = 6), Alzheimer's disease (n = 3), amyotrophic lateral sclerosis (n = 3) and disc herniation with no central nervous involvement (n = 8) participated to determine the CSF ACh levels. RESULTS: Of these 33 patients, the mean ACh level in CSF was 282.2 +/- 61.7 fmol/ml (mean +/- SE, range 20-1505.8 fmol/ml). The mean ACh level of spinocerebellar degeneration group was lower than others, but not statistically significant. CONCLUSION: We conclude that an amount of ACh detectable by RIA is certainly present in CSF.

Acetylcholine↗
PubMed1996

Indonesian medicinal plants. XV. Chemical structures of five new resin-glycosides, merremosides a, b, c, d, and e, from the tuber of Merremia mammosa (Convolvulaceae).

Five new resin-glycosides, named merremosides a (1), b (2), c (3), d (4), and e (5), were isolated from the tuber of Merremia mammosa (LOUR.) HALLIER f. (Convolvulaceae), an Indonesian medicinal plant. The structures of 1, 2, 3, 4, and 5 have been elucidated on the basis of chemical and physiochemical evidence, including syntheses of (11S)-(+)- and (11R)-(--)-jalapinolic acid (16b and 18b) and the glycosidic acid designated as merremoside i (6).

Carbohydrate Sequence↗
PubMed1996

Effect of TA-0910, a novel thyrotropin-releasing hormone analog, on in vivo acetylcholine release and turnover in rat brain.

To examine the action of a novel thyrotropin-releasing hormone (TRH) analog, TA-0910 ((-)-N-[(S)-hexahydro-1-methyl-2,6-dioxo-4-pyrimidinylcarbonyl]-L- histidyl-L-prolinamide tetrahydrate), on the cerebral cholinergic systems, the release of acetylcholine (ACh) and choline in freely-moving rats and ACh accumulation in gamma-butyrolactone (GBL, a nerve impulse flow blocker)- and physostigmine-treated rats were examined. TA-0910 (0.1-1 mg/kg, i.p.) caused a marked dose-dependent increase in extracellular ACh levels and a decrease in choline levels in the hippocampus of freely moving rats. These effects were significantly stronger and longer-lasting than similar effects of TRH. TA-0910 (1, 3 mg/kg, i.p.) depressed the ACh accumulation in the cerebral cortex and hippocampus of GBL (1000 mg/kg, i.p.)-treated rats. Moreover, this analog (1, 3 mg/kg, i.p.) increased the accumulation rate of ACh in these regions in physostigmine (1 mg/kg, i.p.)-treated rats. TRH (30 mg/kg, i.p.) affected the ACh accumulation only in the hippocampus of the GBL-treated rats. These results suggest that TA-0910 not only enhances the release of ACh, but also accelerates the ACh turnover, i.e., ACh release and synthesis, at the cholinergic neuronal terminals in normal rats.

4-Butyrolactone↗
PubMed1996

Boromycin, an anti-HIV antibiotic.

The polyether-macrolide antibiotic, boromycin, was isolated as a potent anti-human immunodeficiency virus (HIV) antibiotic from a fermentation broth of Streptomyces sp. A-3376. Boromycin was found to strongly inhibit the replication of the clinically isolated HIV-1 strain as well as the cultured strain in in vitro laboratory experiments. The mechanism for the anti-HIV activity of boromycin is suggested to involve blocking the later stage of HIV infection, and probably the maturity step for replication of the HIV molecule.

1-Deoxynojirimycin↗
PubMed1996

Pathologic changes in closed porcine intestinal loops inoculated with Aujeszky's disease virus.

Development of enteric lesions in closed jejunal and ileal loops inoculated with Aujeszky's disease virus (ADV) was examined in four 6-week-old SPF pigs. A large number of ADV antigens were detected first in necrotic foci in the subepithelial areas, and subsequently in the epithelial cells, lymphoid follicles in Peyer's patches and neuronal cells of Meissner's and Auerbach's plexuses.

Animals↗
PubMed1996

Reproductive and developmental toxicity studies of toluene. II. Effects of inhalation exposure on fertility in rats.

Male and female Sprague-Dawley rats were exposed to toluene vapor at 600 and 2000 ppm for 6 h/day, and effects on their fertility were investigated. Females were exposed from 14 days before mating until day 7 of gestation. Males were exposed for a total of 90 days, including the mating period; treatment was begun 60 days before pairing, and toxicity with respect to testicular and reproductive functions was examined. In females of the 2000 ppm-treated group, salivation and lacrimation that may have been caused by CNS depression were observed starting 20 days after exposure. Although no abnormalities were seen in mating behavior or fertility, fetal mortality and the number of dams with dead fetuses increased in the 2000 ppm group. In the males exposed to 2000 ppm toluene for 90 days, an increase in kidney weights and a decrease in thymus weights were observed. Basophilic changes and necrosis of kidney tubules were greater at the higher exposure level. Additionally, decreases in the weights of the epididymides and spermatic count were observed, indicating toxicity of toluene to the male reproductive system in vivo for the first time. In conclusion, embryo-fetal toxic effects were apparent in female rats exposed to toluene before and during the early stage of pregnancy. Subacute exposure to a high level (2000 ppm) of toluene vapor elicited mild toxic changes in the kidneys, thymus, and reproductive organs of males. Toxic effects on fertility and reproduction were thus demonstrated not only in females but also in males exposed to toluene vapor in the present study.

Administration, Inhalation↗
PubMed1995

Species differences in the concentration of acetylcholine, a neurotransmitter, in whole blood and plasma.

Various concentrations of acetylcholine (ACh) were detected in samples of bovine, goat, horse, porcine, rat and sheep blood and plasma using a specific, sensitive radioimmunoassay. The ACh levels in whole blood in bovine and horse samples were about 40- and ten-fold higher, respectively, than in humans, but levels comparable to those in humans were measured in porcine samples. Goat, rat and sheep samples had lower whole blood ACh concentrations than those of humans. When plasma samples were assayed, the ACh contents of bovine and porcine plasma were found to be about two- to five-fold those of human. On the other hand, levels in horse, goat, rat and sheep samples were much lower than in humans. The ratio of the ACh contents of plasma to whole blood was high in porcine and rat samples, indicating that porcine and rat blood ACh is distributed mostly in the plasma, while in the other species tested most of the ACh is present in the blood cells. These results demonstrate that variable levels of ACh are present in the blood of different species, and that the distribution of ACh in the blood constituents varies according to species.

Acetylcholine↗
PubMed1995

Transfected mutant p53 gene increases X-ray-induced cell killing and mutation in human fibroblasts immortalized with 4-nitroquinoline 1-oxide but does not induce neoplastic transformation of the cells.

We introduced the mutant p53 gene (codon 273Arg-His) into human fibroblasts (SUSM-I cells) previously immortalized with 4-nitroquinoline I-oxide (4NQO) and obtained 2 clonal cell lines (SUSM-i/p53-1 and SUSM-1/p53-6) expressing the mutant p53. Since the genetic background of SUSM-1/p53 is the same as that of SUSM-1 except for the presence of the mutant p53, we expected to obtain more information on the mechanisms of p53 functions without the influence of other genetic differences by comparing cellular characteristics of both cell lines. SUSM-1/p53 cells became about twice as sensitive to the cytotoxic effects of X-rays as their parent SUSM-1 cells. Mutation frequency was determined by the appearance of hypoxanthine guanine phosphoribosyl transferase deficient (6-thioguanine resistant) cells. As a result, the mutation frequency of SUSM-1/p53 cells was about 5 times that of SUSM-1 cells transfected with or without the vector plasmid alone. Furthermore, when the SUSM-1/p53 cells were exposed to X-rays, the mutation frequency increased to about twice that of the non-irradiated SUSM-1/p53 cells. However, SUSM-1/p53 cells showed neither anchorage-independent growth in soft agar nor tumorigenicity in nude mice. These results indicate that the mutant p53 gene itself, which generally works in a dominant-negative way on cellular carcinogenesis, is not sufficient for neoplastic transformation of immortalized human cells, and that additional genetic change(s) may be necessary for transformation.

4-Nitroquinoline-1-oxide↗
PubMed1995

C-type natriuretic peptide inhibits intimal thickening after vascular injury.

Recently we have found that C-type natriuretic peptide (CNP) inhibits proliferation of cultured rat vascular smooth muscle cells through an elevation of cGMP. We have now tested whether administration of CNP inhibits the development of intimal lesions induced by air-drying injury in rat common carotid arteries in vivo. CNP treatment (1 microgram/kg per min, iv infusion) for either 14 or 5 days resulted in 70% or 60% reduction, respectively, of intimal cross-section area 14 days after injury as compared with control rats. We also found that CNP potently stimulated cGMP production in injured carotid arteries with intimal thickening, but not in intact ones. These results indicate that GC-B, CNP specific receptor/guanylyl cyclase, is expressed at the sites of vascular injury, and that CNP might be efficacious in the prevention of restenosis caused by intimal thickening following coronary angioplasty.

Animals↗
PubMed1995

Tetraploids of the lung fluke Paragonimus westermani found in China.

Two groups of Paragonimus westermani (Tematoda: Platyhelminthes) exist in nature: diploids and triploids. Generally, these two groups live allopatrically, but in Kuandian, Liaoning Province, in the Republic of China, they live sympatrically. In our Chinese experiment on Paragonimus we used metacercariae of P. westermani, which we collected in Kuandian, Xigutai, and performed a cytological analysis. The results were as follows: (1) the P. westermani in Xigutai lived sympatrically as diploids and triploids; (2) all of the small metacercariae were diploids; (3) the large metacercariae were in large proportion triploids; (4) we found one tetraploid specimen in both the medium and the large metacercariae--this was the first time tetraploid lung flukes were discovered; (5) the somatic chromosomes of the tetraploids were different in numbers (4n = 44), but we could not find any difference in the karyotype of haploid sets and that of the diploids and the triploids; (6) unlike the triploids, during their meiosis the tetraploids produced a chromosome pairing, and we found a tendency of the large chromosomes to become quadrivalent; and (7) also unlike the triploids, a great number of spermatids were found in the tetraploid testes. Because of these findings, we can consider tetraploids to be autotetraploids, and these are probably produced by the fertilization of diploids and triploids. We also think that the gametes of tetraploids have a fertilization capability.

Animals↗
PubMed1995

Induction of apoptosis in cultured retinoblastoma cells by the protein phosphatase inhibitor, okadaic acid.

The induction of apoptosis in cultured retinoblastoma cells by diverse drugs was examined by analyzing DNA fragmentation, a hallmark of apoptosis. First, the ability of six retinoblastoma cell lines to undergo apoptosis was surveyed using etoposide (30 micrograms/ml, 20 h exposure). The NCC-RbC-60 cell line, established in this laboratory showed DNA fragmentation clearly, whereas the other cell lines tested, including the representative retinoblastoma cell line, Y-79, did not show distinct DNA fragmentation. Biochemical modulators, such as A23187, forskolin, retinoic acid, phorbol 12-myristate 13-acetate and okadaic acid, were examined to ascertain whether they could induce apoptosis in NCC-RbC-60 and Y-79 cells after exposure for 20 h. Only okadaic acid induced DNA fragmentation in all the retinoblastoma cell lines tested and it induced DNA fragmentation in Y-79 cells in a time- and concentration-dependent manner. Flow-cytometric analysis and microscopic examination revealed that Y-79 cells treated with okadaic acid for 24-48 h accumulated at the G2/M, especially M, phases, before undergoing DNA fragmentation. Other mitotic poisons, nocodazole, colcemid and taxol, also induced apoptosis in Y-79 cells. In the K1034 cell line, established from non-malignant retinal pigmented epithelium, okadaic acid failed to induce both G2/M arrest and DNA fragmentation. These findings suggest that okadaic-acid-induced apoptosis occurs as a result of metaphase arrest.

Apoptosis↗
PubMed1995

Prostacyclin analogue TTC-909 reduces memory impairment in rats with cerebral embolism.

The effects of the stable prostacyclin analogue TTC-909 on memory impairment in the water maze task and on neuronal damage were studied in rats with cerebral embolism induced by injecting polyvinyl acetate (PVA) into the right internal carotid artery and the ensuing embolism extending out into the right middle cerebral artery. Areas supplied by the lenticulostriate artery were most markedly damaged. In the water maze test, the PVA-embolized rats took longer to reach the platform than did the nontreated control rats. To some extent, repeated administrations of TTC-909 (200 ng/kg, IV) overcame this impairment in water maze learning in the rats. We assume that the vasodilating effects of TTC-909 maintain this blood supply to the ischemic area and that TTC-909 prevents the development of thrombosis around the PVA particles in the arterial capillaries, as a result of antiplatelet aggregative effects. These two mechanisms are likely to be involved in memory improvement. TTC-909 may prove effective for treating subjects with stroke and other cerebrovascular disorders.

Animals↗
PubMed1995

Production and characterization of monoclonal antibodies against human natriuretic peptide receptor-A or -B.

Monoclonal antibodies (mAbs) against human natriuretic peptide receptor-A (NPR-A) or NPR-B were produced using NPR-expressing Chinese hamster ovary (CHO) cells and soluble chimeric NPRs consisting of the extracellular domain of each receptor fused to Fc region of human IgG. Three anti-NPR-A mAbs, designated as A144, A397 and A416, bound to human NPR-A but not to NPR-B, while an anti-NPR-B mAb B136 reacted with human NPR-B but not with NPR-A. Competition analysis with the anti-NPR-A mAbs revealed that two mAbs, A144 and A416, recognize an identical or the adjacent site of the receptor and that A397 is directed against another epitope. No anti-NPR-A mAb affected binding of atrial natriuretic peptide (ANP) to NPR-A, while the anti-NPR-B mAb B136 inhibited binding of C-type natriuretic peptide (CNP) to NPR-B. Inhibition of the ligand-binding by B136 is specific in that the mAb showed no effect on the binding of ANP to NPR-A. B136 also blocked CNP-mediated intracellular cGMP accumulation in NPR-B-expressing cells. These results suggest that the region recognized by B136 may be related to the ligand-binding region of NPR-B. NPR-A- and NPR-B-expressing cells were selectively detected by immunostaining using the mAbs. These findings demonstrate that the mAbs will be useful to elucidate the role of the natriuretic peptides and their receptors in normal and disease states in humans [correction of human].

Animals↗
PubMed1995

Role of nitric oxide in the control of blood pressure in young and adult spontaneously hypertensive rats.

1. The depressor response to sodium nitroprusside (SNP) and the pressor response to Nomega-nitro-L-arginine methyl ester (L-NAME) were investigated in anaesthetized and ganglion-blocked 6 week old (young) and 20 week old (adult) spontaneously hypertensive rats (SHR), and the results were compared with those in age-matched normotensive Wistar-Kyoto (WKY) rats. 2. SNP produced a dose-dependent decrease of the mean blood pressure (BP) in both strains, and no differences in vascular sensitivity to SNP were observed between the strains. 3. L-NAME caused dose-dependent pressor responses in both strains. The sensitivity and the maximal response to L-NAME in SHR were significantly greater than those in age-matched WKY (P< 0.05 or 0.01; t-test, 13 d.f. in both ages). However, there were no significant differences in the responses between ages in each strain. 4. Acute reduction of BP induced by 7-O-ethylfangchinoline did not affect the responses to SNP and L-NAME in the adult SHR. 5. These results indicate that a greater amount of NO is tonically released in SHR and that its contribution to BP control is greater in SHR than in WKY, whereas vascular sensitivity to NO does not differ between the strains. In addition, acute changes in BP do not affect the degree of dependency on NO for BP control.

Aging↗
PubMed1995

Antihypertensive effects, determined by a telemetry method, of trichloromethiazide and 7-O-ethylfangchinoline, a derivative of tetrandrine, in spontaneously hypertensive rats.

1. The antihypertensive effects of 10 mg/kg trichloromethiazide (TCM), 10 mg/kg 7-O-ethylfangchinoline (7-O-EFC) and the combination of these drugs given orally once daily for 2 weeks were investigated by measuring the blood pressure (BP), heart rate (HR) and activity in conscious, freely moving spontaneously hypertensive rats (SHR) fitted with a telemetry device. 2. Clear diurnal rhythms of the HR and activity in synchrony with the light/dark cycle were observed during therapy, whereas the BP rhythm was obscure. 3. Alone, TCM and 7-O-EFC produced slight and insignificant reductions of 24h mean BP, whereas in combination they produced an additive and significant BP reduction, compared with the vehicle-treated controls, from the third day of therapy. The BP reduction induced by the combination of these drugs during the dark phase was more marked than that during the light phase. 4. None of the drug therapies affected the HR and activity diurnal rhythms. 5. The results of the present study demonstrate that the telemetry method is useful for monitoring the antihypertensive effects of drugs in SHR under physiological conditions with minimal stress.

Alkaloids↗