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Biomedical subjects

K Kawashima

Publications and source records attributed to K Kawashima.

At least 73 records · Page 4Linked to original sources
PubMed2000

Experience with 24 cases of reconstructive anterior skull base surgery: classification and evaluation of postoperative facial appearance.

This article details our experience with 24 cases of anterior skull base reconstruction after tumor resection. They were classified into four types according to the resected region. In 11 cases of type I resection, the orbital part of frontal bone and/or cribriform plate of ethmoid bone were resected. In two cases of type II resection, the orbital contents and partial orbital bone were resected with the addition of type I. In five cases of type III resection, the maxillary bone was resected with the addition of type II. In six cases of type IV resection, the zygomatic bone and/or facial skin were resected with the addition of type III. The tumor originating from intracranial region was 25% of this series and all of them belonged to type I. The tumor originating from extracranial region tumor was 75% and its resected region was more extensive. In type I and II resections, the cranial flap, radial forearm free flap, or a combination of the two was used for reconstruction. The rectus abdominis myocutaneous/muscle free flap was used for reconstruction of massive defects in type III and IV defects. Total incidence of postoperative complications was 16.7%. Donor site deformity of the cranial flap at the frontal and temporal region in types I and II resections and facial contour deformity in zygomatic region and defect of upper and/or lower palpebra in type IV resection were major problems with postoperative facial appearance. Although use of the rectus abdominis myocutaneous free flap combined with costal cartilages improved the midfacial contour, palpebral reconstruction remained an unsolved problem in reconstructive skull base surgery. The reconstructive goals in skull base surgery are not only to obtain safe and reliable skull base reconstruction but also to restore the facial appearance postoperatively.

Journal Article↗
PubMed2000

Effect of bicozamycin on the eradication of Shiga toxin-producing Escherichia coli in calves.

Fifty-nine calves, aged 11 days to 9 months, from three farms breeding Japanese Black beef cattle in Miyazaki Prefecture, Japan, were examined for the presence of Shiga toxin-producing Escherichia coli (STEC). A high prevalence of STEC was detected among calves, with 45 (76.3%) animals carrying STEC including different serogroups (O26, O74, O111, O114, O119, O127, O153, O157, and ONT) and toxin types. The number of STEC in the feces was estimated by a combined method involving enumeration of colony-forming units by a plate-most-probable-number (plate-MPN) technique and polymerase chain reaction for the detection of Shiga toxin genes. Fecal shedding ranged from 10(1) to 10(10) MPN/g feces. To evaluate the safety and efficacy of bicozamycin (BCM: previously named as bicyclomycin) in eradicating STEC, 30 calves carrying STEC with or without diarrhea were examined. Fifteen calves were treated orally with BCM (10 mg/kg/day) once daily for 5 days, and the other 15 were untreated. Twenty-four hours after the last dose, fecal specimens were collected from both groups to compare the number of coliforms and STEC with those before treatment. BCM-treated animals had a significantly lower number of coliforms and STEC compared to the untreated calves. The STEC eradication rate was 86.6% (13/15) in the BCM-treated group, compared to 0% (0/15) in the control group. The corresponding cure rates for diarrhea were 87.5 (7/8) and 0% (0/3), respectively. No adverse reactions were observed in the calves during treatment. It is concluded that BCM is an effective agent for the eradication of STEC in calves with or without diarrhea.

Animals↗
PubMed2000

Bidirectional effects of hypergravity on the cell growth and differentiated functions of osteoblast-like ROS17/2.8 cells.

A low level of hypergravity (1.5-2.0 G) stimulated the proliferation of ROS17/2.8 cells, whereas it inhibited the differentiated functions of alkaline phosphatase activity and osteocalcin synthesis. These results were just the opposite of our results obtained when the cells were exposed to a high level of hypergravity (40-80 G): inhibition of cell growth and the stimulation of the differentiated functions. The direction of change in the cAMP contents of the cells was also reversed, with a low level of hypergravity causing a decrease in the cAMP content and a high level of hypergravity an increase in it. Therefore, bidirectional effects of hypergravity on the growth and differentiated functions exist in ROS17/2.8 cells according to the magnitude of the hypergravity.

Alkaline Phosphatase↗
PubMed2000

Species differences in oral bioavailability of methotrexate between rats and monkeys.

The contributions of incomplete absorption and a first-pass effect to the low bioavailability (BA) of methotrexate (MTX) were evaluated pharmacokinetically in rats and monkeys which respectively have a lower and higher aldehyde oxidase (AO) activity than humans. Plasma concentration profiles of MTX in rats showed linear and nonlinear pharmacokinetics respectively after intravenous (i.v.) and oral dosing of 0.1, 0.5 or 2.5 mg/kg MTX. In rats, most of the dose was excreted as the parent compound into bile and urine after i.v. dosing of 0.5 mg/kg MTX, while the radioactivity was largely eliminated in expired air after oral dosing of 0.5 mg/kg 14C-MTX. Elimination in expired air fell markedly following antibiotics treatment. 7-Hydroxymethotrexate (7-OH-MTX), formed from MTX by AO, was detected in monkey plasma after i.v. and oral dosing of 0.5 mg/kg MTX, but not in rat plasma. The ratio of the cumulative urinary excretion of 7-OH-MTX to MTX in monkeys was higher after oral dosing than after i.v. dosing. The low BA in rats (10% at 0.5 mg/kg) was shown to be mainly due to incomplete absorption, including limited absorption and degradation to 2,4-diamino-N10-methylpteroic acid (DAMPA) and glutamic acid (Glu) by the carboxypeptidase of intestinal bacteria. The low BA in monkeys (5% at 0.5 mg/kg) was shown to be mainly due to the extensive first-pass effect, including metabolism to 7-OH-MTX.

Animals↗
PubMed2000

Pharmacological properties of traditional medicines. XXVI. Effects of Sansohnin-to on pentobarbital sleep in stressed mice.

We investigated the effect of Sansohnin-to (SAT) on changes of duration in sodium pentobarbital (PB)-induced sleeping time caused by five types of stress. SAT reversed shortened PB sleep in repeated cold stress or 45 min-restraint stress tests and the prolonged PB sleep in 120 min-restraint stress. SAT did not reverse the shortened PB sleep in the specific stress state caused by an alternating rhythm in temperature stress or social isolation stress. In addition, SAT influenced both shortened PB sleep in 45 min-restraint stress and prolonged PB sleep in 120 min-restraint stress. SAT had no effect on PB sleep in unstressed control mice. These findings suggest that SAT has unusual activity, different from synthetic narcoleptics such as benzodiazepine. This is because SAT had no effect on PB sleep in unstressed mice, and it reverses stress-induced decrease and/or increase in PB sleep by improving stress-induced functional changes in the central nervous system, rather than by acting like a synthetic hypnotic on the gamma-aminobutyric acidA (GABA(A)) receptor.

Administration, Oral↗
PubMed2000

Calcium signaling and c-Fos gene expression via M3 muscarinic acetylcholine receptors in human T- and B-cells.

We previously showed that blood acetylcholine (ACh) originates mainly from T-lymphocytes, and that stimulation of muscarinic ACh receptors (mAChRs) induces Ca2+ oscillations and up-regulates c-fos gene expression in both T- and B-lymphocytes. In the present study, we investigated which mAChR subtypes are involved in Ca2+ signaling and c-fos gene expression in human T- (CEM) and B- (Daudi) cells. Stimulation of mAChRs with 100 microM oxotremorine-M, an M1/M3 agonist, increased levels of intracellular free Ca2+ ([Ca2+]i) and c-fos mRNA expression in both cell lines. 4-DAMP, an M3 antagonist, more effectively blocked the oxotremorine-M-induced increase in [Ca2+]i than pirenzepine and telenzepine, M1-receptor antagonists; AF-DX 116, an M2 antagonist; hexahydrosiladifenidol, a weak M3 antagonist; or hexamethonium and d-tubocurarine, nicotinic receptor antagonists. McN-A-343 (100 microM), a partial M1-receptor agonist, had no apparent effect on [Ca2+]i in either cell line. The oxotremorine-M-induced up-regulation of c-fos transcription was inhibited by 4-DAMP, but not by pirenzepine or AF-DX 116. Our findings thus suggest that ACh released from T-lymphocytes acts as an autocrine/paracrine factor, transmitting a Ca2+-dependent signal to the nuclei of T- and B-lymphocytes via M3 receptors.

Analysis of Variance↗
PubMed2000

Comparative immunohistopathology in pigs infected with highly virulent or less virulent strains of hog cholera virus.

Eight pigs were inoculated subcutaneously with a highly virulent hog cholera virus (HCV) strain ALD. The infected pigs developed severe illness and became moribund on postinoculation day (PID) 7 or PID 10. Histologic lesions were characterized by severe generalized vasculitis, necrosis of lymphocytes, and encephalitis. HCV antigen was detected in crypt tonsilar epithelial cells, macrophages, and reticular endothelial cells of lymphoid tissues. Antigen localization corresponded well with histologic lesions. Five pigs were inoculated with less virulent HCV Kanagawa/74 strain and were euthanatized on PID 30. All five infected pigs recovered from the illness but became stunted. They also had a slight follicular depletion of lymphocytes, histiocytic hyperplasia, and hematopoiesis in the spleen. Less virulent HCV antigen was observed in the tonsils, kidneys, pancreas, adrenal glands, and lungs. Although antigen localization was less associated with histologic lesions, immunoreactivity was stronger than that in the pigs infected with the ALD strain of HCV. An almost complete loss of B lymphocytes was recognized in pigs infected with the ALD strain and was correlated with follicular necrosis in lymphoid tissues. Loss of B lymphocytes was not prominent in the pigs infected with Kanagawa/74 strain. The number of CD4+ and CD8+ T lymphocytes was significantly higher than that in the noninfected control pigs.

Animals↗
PubMed2000

Involvement of phosphoinositide-3-kinase and p70 S6 kinase in regulation of proliferation of rat lactotrophs in culture.

Phosphoinositide-3-kinase (PI-3K) and p70 S6 kinase (p70S6k) are suggested as important molecules for mediating mitogenic actions of growth factors and cytokines in a variety of cell types. The purpose of the present study was to investigate whether these kinases were involved in mediation of the mitogenic actions of not only the growth factor insulin but also cyclic adenosine monophosphate (cAMP) and estrogen on rat cultured lactotrophs. Treatment with wortmannin or LY294002, a PI-3K inhibitor, or rapamycin, a p70S6k inhibitor, decreased basal levels of 5-bromo-2-deoxyuridine (BrdU)-labeling indices of lactotrophs in a dose-dependent manner. These inhibitors were effective in blocking an increase in BrdU-labeling indices induced by insulin. LY294002 and rapamycin also suppressed an increase in BrdU-labeling indices induced by forskolin, an adenylate cyclase activator, or dibutyryl cAMP, a membrane-permeable cAMP analog, as well as that induced by estradiol, a physiologic extracellular activator of lactotroph proliferation. However, the dibutyryl cAMP-, but not insulin-induced proliferation, acquired a resistance to LY294002 and rapamycin by pretreatment with bromocriptine, a dopaminergic agonist that is able to suppress lactotroph proliferation. These results suggest that the mitogenic actions of cAMP and estradiol on rat lactotrophs are mediated by PI-3K and p70S6k, and that dopaminergic inhibition modifies the PI-3K and p70S6k dependence of the regulation of lactotroph proliferation.

Adenylyl Cyclases↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats--overview of the studies.

The National Institute of Health Sciences and 28 member companies of the Japan Pharmaceutical Manufacturers Association (JPMA) have conducted a validation study intended to examine whether or not lesions in the male reproductive organs noted in 4-week treatment studies can also be detected after 2-week treatment. In this study, lesions in the male reproductive organs after 2-week treatment were, therefore, compared with those after 4-week treatment. A total of 24 test substances was evaluated, these being nucleic acid modulators, cell division inhibitors, central hormonal modulators, hormonal drugs and their antagonists, other drugs and general chemicals. Among these substances, theophylline did not cause any appreciable lesions in the male reproductive organs even after 4-week treatment in the preliminary studies. With busulfan, data reported in the literature was not reproduced in the preliminary study and all animals died. Therefore, detailed examinations were not conducted for busulfan and theophylline. The remaining 22 test substances, when given to animals for 2 weeks at doses equal to or higher than for 4-week treatment, caused lesions similar to those noted after 4 weeks. It is evident from these findings that effects of pharmaceuticals on the male reproductive organs can be detected in most cases with 2-week treatment.

Animals↗
PubMed2000

[Autologous blood transfusion in surgery of urologic malignant tumor].

BACKGROUND: Autologous blood transfusion has been widely endorsed, because of the adverse effects attributed to homologous blood transfusion. So we employed autologous blood transfusion to avoid homologous blood transfusion in operation of urological malignant patients. We reviewed our experience with autologous blood transfusion in 48 patients. METHODS: A total of 48 patients underwent operation with 400 to 1,200 ml preoperative autologous blood donation, in 41 patients with administration of erythropoietin and 7 patients without erythropoietin. The details of operations are radical nephrectomy in 18 cases (2 cases were bilateral), radical nephro-ureterectomy in 2 cases, retroperitoneal lymph node dissection (RPLND) in 2 cases, radical prostatectomy in 12 cases and radical cystectomy in 14 cases. RESULTS: The volume of surgical blood loss were 381 +/- 522 ml in nephrectomy (1,158 +/- 202 ml in bilateral case), 517 +/- 5 ml in radical nephro-ureterectomy 636 +/- 574 ml in RPLND, 665 +/- 291 ml in radical prostatectomy and 1,123 +/- 417 ml in radical cystectomy. Only three cases needed homologous blood transfusion. CONCLUSION: We can avoid homologous blood transfusion in 94% of patients. Autologous blood transfusion is recommended as safe and convenient.

Adult↗
PubMed2000

[Efficacy of combined chemoendocrine therapy with doxifluridine, cyclophosphamide, and fadrozole hydrochloride hydrate in a case of stage T4N3M1 breast cancer].

A 66-year-old female presented with a swollen lump in the left breast. She was diagnosed as having advanced breast cancer of stage T4N3 (supraclavicular lymph node) M1 (bone). The administration of CEF and TAM failed to improve her condition. After the treatment regimen was changed to combined chemoendocrine therapy with CPA, EPI, 5'-DFUR, and MPA, the areas of bone metastases were reduced. However, MPA caused side-effects (acute obstruction of the lower limb), and thus the treatment was discontinued after 4 months. Subsequently, the treatment combination was changed to CPA, EPI, 5'-DFUR, and fadrozole hydrochloride hydrate. After one year of the treatment, a complete response (CR) was obtained with the disappearance of the supraclavicular lymph node and bone metastases. After EPI reached the maximum administration amount, the remaining CPA, 5'-DFUR and fadrozole hydrochloride hydrate oral administrations were continued. As of 3 years and 10 months after the onset of the chemoendocrine therapy, CR has been maintained with suppression of the primary and metastatic lesions, without degrading the patient's quality of life.

Administration, Oral↗
PubMed2000

Enhancement of hippocampal cholinergic neurotransmission through 5-HT1A receptor-mediated pathways by repeated lithium treatment in rats.

Hippocampal cholinergic neuronal activity is reported to be regulated, at least partly, through serotonin1A (5-HT1A) receptors. Chronic lithium treatment has been shown to alter both behavioral and neurochemical responses mediated by postsynaptic 5-HT1A receptors. We investigated whether long-term lithium treatment affects central cholinergic neurotransmission through 5-HT1A receptor-mediated pathways. Changes in acetylcholine (ACh) release induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, in the rat hippocampus were measured using a microdialysis technique and a radioimmunoassay for ACh. Administration of lithium for 21 days resulted in a serum lithium concentration of 1.03 mM and caused little change in density or affinity of [3H]8-OH-DPAT binding sites in the hippocampus. The local application of 8-OH-DPAT into the hippocampus of lithium treated rats increased the ACh efflux in both the absence and the presence of physostigmine, a cholinesterase (ChE) inhibitor, in the perfusion fluid. The basal ACh efflux of lithium treated rats was not different from that of the control rats under normal conditions, but was significantly higher than that of the controls when ChE was inhibited. These results demonstrate that chronic lithium treatment increases spontaneous ACh release in the hippocampus under conditions of ChE inhibition, but not under normal conditions, and enhances cholinergic neurotransmission through 5-HT1A receptor-mediated pathways, and suggest that activation of 5-HT1A receptor function by lithium is related to the enhancement of hippocampal cholinergic neurotransmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

[Clinical features of multiple primary cancers including prostate cancer].

We analyzed the clinical features of multiple primary cancers (MPCs) that included prostate cancer. MPCs were observed in 93 (15.2%) of the patients suffering from prostate cancer. In the MPC group, the organ most commonly involved was the stomach, followed by bladder, colon and lungs. The median age at diagnosis of the first, second and third cancers was 72, 74, and 75 years old, respectively, and the duration between the first and second cancers (median: 20 months) was longer than that between the second and third cancers (median: 8 months). In the 37 MPC patients whose cause of death was obvious, 29 (78.4%) died of a cancer; prostate cancer was not so common (6 patients) as the cause of death. Age at diagnosis and grade distribution of prostate cancer were not significantly different between the MPC and single primary cancer (SPC) groups. However, the proportion of earlier stage was significantly (p < 0.01) higher in the MPC group than in the SPC group, and this trend was more obvious in patients whose prostate cancer was diagnosed as the second cancer. The prostate cancer-specific survival rates were significantly higher in the patients with MPC, and this trend was more obvious in the patients with stage D or moderately differentiated cancer. It is important in the follow up of prostate cancer patients to be aware of the possibility of the occurrence of a second cancer.

Age Factors↗
PubMed1999

Toluene inhalation induced epididymal sperm dysfunction in rats.

Toluene is a widely abused inhaled solvent. This study was designed to determine whether toluene abuse affects the reproductive functions or general health of males. Seven-week-old male Sprague-Dawley rats were exposed to toluene vapor inhalation (0, 4000, or 6000 ppm; 2 h/day) daily for 5 weeks. Exposure-related suppression of body weight gain and food consumption were observed. Salivation and lacrimation were observed during exposure periods and intensified with repeated exposure. Rats exposed to 6000 ppm toluene had decreased spleen and thymus weights, as well as suppressed lymphocyte counts. In 6000 ppm group, the epididymal sperm counts, sperm motility, sperm quality and in vitro penetrating ability to zona-free hamster eggs were significantly reduced, while no exposure-related changes in the testes weight or spermatogenesis within testes were detected. Tail-less sperm heads were seen within zona-free eggs incubated with sperm from rats exposed to 6000 ppm toluene, but not control rats. No significant changes were observed in serum luteinizing hormone, follicle-stimulating hormone, or testosterone levels following 1 month of exposure to 6000 ppm toluene. These results indicate that high concentrations of toluene may directly target sperm in the epididymis and disrupt sperm maturation.

Animals↗
PubMed1999

Changes in macrophage and lymphocyte subpopulations of lymphoid tissues from pigs infected with the porcine reproductive and respiratory syndrome virus (PRRSV).

We used an immunohistochemical method to investigate changes in macrophage and lymphocyte subpopulations in various lymphoid tissues of pigs in the acute phase of porcine reproductive and respiratory syndrome virus (PRRSV) infection. The numbers of CD8+ cells and B-cells varied among lymphoid tissues after PRRSV infection. In the infected pigs, numbers of CD8+ cells increased in systemic lymphoid tissues whereas numbers of B-cells increased in mucosa-associated lymphoid tissues. There was no difference in the distribution of virus-infected cells and macrophages between lymphoid tissues of the infected pigs. These changes may be associated with the establishment of virus persistence or the emergence of concurrent infection in mucosal organs.

Animals↗
PubMed1999

Nardosinone, a novel enhancer of nerve growth factor in neurite outgrowth from PC12D cells.

We isolated nardosinone as a neuritogenic substance from Nardostachys chinensis. Nardosinone did not exhibit the neurotrophic activity but caused a marked enhancement of the nerve growth factor (NGF)-mediated neurite outgrowth from PC12D cells. Nardosinone-induced enhancement of the NGF-action was completely blocked by PD98059, a representative mitogen activated protein kinase (MAPK) kinase inhibitor. The microscopic observations indicated that the neurites in response to nardosinone and NGF were quite long and were generally extended to the neighboring cells. These results suggest that nardosinone enhances the NGF-induced neurite outgrowth from PC12D cells probably by amplifying an up-stream step of MAPK kinase in the NGF receptor-mediated intracellular signaling pathway.

Animals↗
PubMed1999

Establishment of permanent cell lines exhibiting vitamin D-dependent expression of beta-galactosidase activity.

The active hormonal form of vitamin D3, 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), has been described as a principal mediator of skeletal homeostasis. Treatment of rat osteosarcoma (ROS)17/2.8, an osteoblast-like cell line, with 1alpha,25(OH)2D3 results in a ligand-dependent increase in transcription of the bone-specific osteocalcin gene. We isolated permanent cell lines that were established by transfecting ROS 17/2.8 cells with plasmids consisting of the human osteocalcin gene promoter containing the vitamin D responsive element linked to a bacterial beta-galactosidase gene. In one of many cell lines, especially in clone NK-31, 1alpha,25(OH)2D3 strongly stimulated beta-galactosidase activity. Reverse transcription-polymerase chain reaction analysis also showed endogenous osteocalcin gene expression and beta-galactosidase gene expression in clone NK-31 cells, which paralleled the increase in beta-galactosidase activity. Using a synthetic analogue of 1alpha,25(OH)2D3, 24,24-difluoro-1alpha,25-dihydroxyvitamin D3, we found that the levels of this activity and these gene expressions were nearly parallel to those of 1alpha,25(OH)2D3. 24R,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 at high doses (concentration: 10(-7) M) also induced beta-galactosidase activity in clone NK-31. These cell lines, harboring the plasmid-carrying beta-galactosidase gene under the control of the osteocalcin gene promoter, may contribute to studies on the regulation by 1alpha,25(OH)2D3 or to the development of synthetic analogues of 1alpha,25(OH)2D3.

Animals↗