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Biomedical subjects

K Hayakawa

Publications and source records attributed to K Hayakawa.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effects of beta-adrenergic stimulation on the acutely obstructed ureter in dogs.

The objective of the present study was to evaluate the effects of a selective beta(3)-adrenoceptor agonist, (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1, 3-benzodioxole-2,2-dicarboxylate (CL 316243), on the acutely obstructed ureter in anesthetized dogs. After a complete ureteral obstruction produced by the inflation of a balloon catheter placed within the left lower ureter, the intraluminal ureteral pressure gradually rose to reach a plateau of approximately 52.5 mm Hg. Intravenous administration of isoproterenol (a nonselective beta-adrenoceptor agonist; 10 microg/kg) and CL 316243 (1 microg/kg) significantly decreased this elevated ureteral pressure (by 74.1 and 77.2%, respectively), with the reduction more sustained with CL 316243 than with isoproterenol. In addition, under both isoproterenol and CL 316243, urine flow (which had been interrupted by the balloon) was resumed, resulting in further sustained decreases in ureteral pressure. The mean blood pressure decreased and heart rate increased after the administration of both drugs, but these changes were greater in the isoproterenol group than in the CL 316243 group. In contrast, i.v. administration of butylscopolamine (an anticholinergic agent; 1000 microg/kg) had no evident effects on ureteral pressure or on urine flow. The increase in left kidney weight seen after ureteral obstruction was suppressed by CL 316243. We conclude that the selective beta(3)-adrenoceptor agonist tested appears to be more useful than isoproterenol for reducing ureteral pressure above the obstructed site and for promoting ureteral relaxation and increasing urine flow around the point of obstruction in dogs.

Adrenergic beta-Agonists↗
PubMed2000

[Clinical results of selective laser trabeculoplasty].

PURPOSE: Selective laser trabeculoplasty (SLT) is a new technique aimed to developed to impact pigmented trabecular cells selectively. Compared with ordinary argon laser trabeculoplasty, it is expected to have fewer complications with more efficacy for open-angle glaucoma. In this study we performed SLT on 17 eyes of 10 patients with primary open-angle glaucoma and 1 eye with capsular glaucoma. METHODS: Follow-up period was up to 10 months. Average energy irrachieted was 28.14 mJ (0.47 mJ x 59 spots) against pigmented trabecular band over the half circumference of anterior chamber angle. RESULTS: Preoperative mean intraocular pressure (IOP) was 22.8 mmHg and postoperative mean IOP was decreased significantly to 8.6, 17.3, and 16.1 mmHg at 1, 3, and 6 months after treatment, respectively. The average maximum IOP reduction was 8.8 (3-18) mmHg after SLT. Among 11 eyes showing transient IOP elevation, 6 eyes had an elevation of more than 5 mmHg. No remarkable postoperative complications were noted. CONCLUSION: SLT is a safe and effective modality for the treatment of open-angle glaucoma such as primary open-angle glaucoma (POAG) and capsular glaucoma.

Adult↗
PubMed2000

[Recent advances of radiation therapy for non-small cell lung cancer].

Radiation therapy(RT) has been frequently used for patients with inoperable or unresectable non-small cell lung cancer(NSCLC). In our series of NSCLC patients without progression of disease at the end of two years after RT, the majority of squamous cell carcinoma patients were alive well after 5 years from RT. On the other hand, half of adenocarcinoma patients had distant failures later. The recent data have indicated that the prognosis for selected favorable patients with unresectable disease will be improved by systemic chemotherapy combined with RT. Furthermore recent innovations in RT have shown promise in the treatment of NSCLC, especially squamous cell carcinoma. For future improvement of the treatment results of NSCLC, it is important that the role of RT be established.

Brachytherapy↗
PubMed2000

B-cell commitment, development and selection.

Here we review three areas in B-cell development in the mouse, with a focus on relevance to B-1/CD5+ B cells. Multiparameter flow cytometry has allowed the dissection of intermediate stages of developing B cells, both in fetal liver and bone marrow. In the first area, we present recent work that has delineated a fraction of pre-pro-B cells, committed to the B lineage, but lacking any immunoglobulin rearrangements. Next, the role of the pre-B-cell receptor in B-cell repertoire selection has become clear in the past few years, but we present work suggesting that the action of this process during fetal life is different, resulting in selection of a very distinct repertoire compared with adult. Finally, we describe a new VH3609 antithymocyte Ig transgenic mouse model system that has provided the first definitive evidence for the role of self-antigen in development and maintenance of natural autoreactive B cells.

Animals↗
PubMed2000

Immunohistochemical expression of glutathione transferase-pi in untreated primary non-small-cell lung cancer.

Patients with unresectable non-small-cell lung cancer (NSCLC) usually have undergone chemotherapy; however, such problems as resistance to chemotherapeutic agents occur during the treatments. Recent studies have indicated that glutathione S-transferase-pi (GST-pi) may play an important role in the resistance of cancer cells to alkylating agents, including cisplatin compounds. We examined a possible relationship between immunohistochemical expression of GST-pi and the response to cisplatin plus etoposide chemotherapy in patients with untreated and unresectable primary NSCLC. Of the 89 patients, 50 (56.2%) were GST-pi-positive and 39 (43.8%) were GST-pi-negative. For the patients with negative GST-pi expression, the response rate was 66.7% (26 of 39 patients). In the patients with positive GST-pi expression, the response rate was 26% (13 of 50 patients). This difference was statistically significant (P = .0019). The results suggest that GST-pi expression in NSCLC tissues is related to response to cisplatin plus etoposide chemotherapy and may be useful as a predictor of chemotherapy response.

Adenocarcinoma↗
PubMed2000

Existence of a beta3-adrenoceptro and its functional role in the human ureter.

PURPOSE: We tried to determine the beta-adrenoceptor (AR) subtypes distributed in the human ureter and to clarify their functional role in ureteral relaxation. MATERIALS AND METHODS: 1) Effects of beta-AR agonists on either spontaneous or KCl-induced contractions of the human ureter and the antagonism by beta-AR antagonists on isoprenaline (a non-selective beta-AR agonist)-induced effects were evaluated in vitro. 2) Displacement by beta-AR antagonists of [3H]-dihydroalprenolol binding to a membrane preparation derived from human ureteral smooth muscle was evaluated. 3) A reverse transcription polymerase chain reaction assay was performed to determine the expression of the mRNA for beta1-, beta2- and beta3-ARs in human ureteral smooth muscle. RESULTS: 1) Isoprenaline and procaterol (a beta2-AR agonist) concentration-dependently suppressed both spontaneous and KCl-induced contractions of the human ureter. The beta3-AR agonists, CGP-12177A and CL-316243, also suppressed these ureteral contractions, but dobutamine (a beta1-AR agonist) had little relaxing effect. The rank order of relaxing potency for the catecholamines was isoprenaline > adrenaline > noradrenaline. ICI-118,551 (a beta2-AR antagonist) only partially antagonized the isoprenaline-induced relaxation. 2) Propranolol (a non-selective beta-AR antagonist) and ICI-118,551 concentration-dependently displaced [3H]-dihydroalprenolol binding to the membrane with Ki values of 1.5 x 10-9 M and 6.3 x 10-9 M, respectively, while metoprolol (a beta1-AR antagonist) was less effective in this assay. 3) beta1-, beta2- and beta3-AR mRNAs were all expressed in human ureteral smooth muscle. CONCLUSION: The present results provide the first evidence that the beta3-AR subtype is distributed in human ureteral smooth muscle and that it, and beta2-AR, mediate the ureteral relaxation induced by adrenergic stimulation.

Adult↗
PubMed2000

[A case of idiopathic subglottic stenosis successfully treated with endoscopic laser treatment].

A 24-year-old woman presented with an abnormal sound in her neck. She had no history of previous surgery, endotracheal intubation or neck trauma. She had been aware of this abnormal sound since she was 12 years old, but paid no attention to it. She had been recommended to visit a hospital for a neck examination. Stridor was heared in the neck ["coming from the throat"?]. Peak flow was markedly suppressed in pulmonary function tests, and the flow volume loop indicated upper airway stenosis. Bronchoscopy revealed subglottic tracheal stenosis, and magnetic resonance imaging showed that the cricoid cartilage was normal. Nd-YAG laser treatment was performed in Mitsui Memorial Hospital and her symptoms were improved. Biopsy of the stenotic area of the trachea showed dense fibrous tissue proliferation in the submucosa. Neither granuloma nor vasculitis was found in the biopsy specimen. No systemic disease capable of inducing tracheal stenosis was found on systemic examination. From these clinical and pathological findings, we diagnosed idiopathic subglottic stenosis.

Adult↗
PubMed2000

Parotid gland papillary cystadenocarcinoma in a Fischer 344 rat.

A spontaneous parotid gland tumor with histomorphologic features characteristic of cystic and papillary growth was found in a 72-week-old F344 rat. The tumor had a prominent cystic appearance and invasive growth into the dermis beyond the muscular layer of the skin. The cyst walls were lined by a single layer of cuboidal to tall columnar epithelium with prominent papillary projections continuous with the cyst lining. The tumor cells had mucoid, pale cytoplasm and medium to large nuclei. The myoepithelium did not appear to be associated with the tumor cysts and the papillae. Atrophic parotid gland tissues were seen between cysts and in the periphery of the cystic lesions. In light of these findings, the tumor was diagnosed as papillary cystadenocarcinoma of parotid gland; this is the first description of a salivary gland papillary cystadenocarcinoma in a rat.

Animals↗
PubMed1999

Peripheral CD4+ T cell maturation recognized by increased expression of Thy-1/CD90 bearing the 6C10 carbohydrate epitope.

The SM6C10 IgM autoantibody recognizes a surface determinant, 6C10, that is highly expressed on all immature thymocytes. In contrast, its expression on peripheral T cells appears developmentally regulated, i.e., absent from most naive T cells in spleen of neonatal mice, but expressed on 40-80% of naive CD4+ T cells in adult. In this paper, we demonstrate that SM6C10 recognizes a carbohydrate epitope on the Thy-1 glycoprotein using immunoprecipitation analysis, by binding to affinity-purified Thy-1 in an ELISA, and by sensitivity to N-glycosidase-F treatment. Retroviral Thy-1 gene transduction experiments into Thy-1- variant T cell lines and a pro-B cell line provide evidence that 6C10 glycosylated Thy-1 expression is not restricted to T cells but depends on the recipient cell. Therefore, differences in 6C10 levels among Thy-1+ T cells in mice likely reflect developmental regulation of posttranslational modification of the Thy-1 glycoprotein. The ability of naive CD4+ T cells to respond to anti-Thy-1 stimulation increases from neonate to adult, and 6C10- naive cells from adult mice respond poorly compared with 6C10+ cells, similar to the cells in neonatal mice. These results suggest that there is functional maturation by peripheral CD4+ T cells that coincides with 6C10 glycosylated Thy-1 up-regulation, and natural autoantibody recognizes this 6C10 carbohydrate epitope.

Animals↗
PubMed1999

Nerve growth factor prevention of aged-rat sympathetic neuron injury by cisplatin, vincristine and taxol--in vitro explant study.

We examined the preventive effects of nerve growth factor (NGF) against neurotoxicity induced in aged rats by anticancer drugs such as cisplatin, vincristine and taxol using a superior cervical ganglion explant culture system. The inhibition of neurite outgrowth by cisplatin, vincristine and taxol was markedly prevented by co-treatment with NGF. The neurite and nerve cell populations were well preserved in vincristine and taxol, whereas cisplatin reduced these populations as compared with control even when treated with NGF. These results indicate that, just as in young adult rats, NGF prevents toxic sympathetic nerve injury induced by vincristine and taxol even in aged rats, but does not protect against cisplatin-induced nerve cell injury.

Aging↗
PubMed1999

Distinct in vivo and in vitro cytokine profiles of draining lymph node cells in acute and chronic phases of contact hypersensitivity: importance of a type 2 cytokine-rich cutaneous milieu for the development of an early-type response in the chronic phase.

Although regional lymph nodes (LN) have been extensively studied as rich sources of effector T cells in contact hypersensitivity (CH), it remains unknown whether T cell responses in the LN reflect those in effector skin sites. We previously showed that repeated elicitation of CH results in a shift in the time course of Ag-specific CH from a delayed-type hypersensitivity response to an early-type response, a reflection of a shift in cutaneous cytokine expression from a type 1 to a type 2 profile. To investigate whether repeated elicitation of CH could also drive T cell development to the type 2 phenotype in the regional draining LN, sequential cytokine gene expression after hapten application was assessed during both the acute and the chronic phase of CH. In the draining LN the shift to type 2 cytokine production was also observed, but more mixed patterns of responses were induced than in the corresponding skin sites. The chronic LN cells (LNC), when stimulated in vitro, produced markedly lower levels of type 1 cytokines and higher levels of type 2 cytokines than the acute LNC. A successful passive transfer of an early-type response by the LNC was only induced in the recipient mice when the skin sites chronically treated with hapten were elicited. These results indicate that an early-type response by regional LNC would take place only in a milieu with sufficient levels of type 2 cytokines.

Acute Disease↗
PubMed1999

Positive selection of natural autoreactive B cells.

Lymphocyte development is critically influenced by self-antigens. T cells are subject to both positive and negative selection, depending on their degree of self-reactivity. Although B cells are subject to negative selection, it has been difficult to test whether self-antigen plays any positive role in B cell development. A murine model system of naturally generated autoreactive B cells with a germ line gene-encoded specificity for the Thy-1 (CD90) glycoprotein was developed, in which the presence of self-antigen promotes B cell accumulation and serum autoantibody secretion. Thus, B cells can be subject to positive selection, generated, and maintained on the basis of their autoreactivity.

Aging↗
PubMed1999

Characterization of the myosin light chain kinase from smooth muscle as an actin-binding protein that assembles actin filaments in vitro.

In addition to its kinase activity, myosin light chain kinase has an actin-binding activity, which results in bundling of actin filaments [Hayakawa et al., Biochem. Biophys. Res. Commun. 199, 786-791, 1994]. There are two actin-binding sites on the kinase: calcium- and calmodulin-sensitive and insensitive sites [Ye et al., J. Biol. Chem. 272, 32182-32189, 1997]. The calcium/calmodulin-sensitive, actin-binding site is located at Asp2-Pro41 and the insensitive site is at Ser138-Met213. The cyanogen bromide fragment, consisting of Asp2-Met213, is furnished with both sites and is the actin-binding core of myosin light chain kinase. Cross-linking between the two sites assembles actin filaments into bundles. Breaking of actin-binding at the calcium/calmodulin-sensitive site by calcium/calmodulin disassembles the bundles.

Actin Cytoskeleton↗
PubMed1999

Increased expression of phospholipase D1 mRNA during cAMP- or NGF-induced differentiation in PC12 cells.

The rat pheochromocytoma PC12 cells have been employed as a useful model to study neuronal differentiation. To gain insight into the molecular events involved in extension of neurites, the differential expression of phospholipase D (PLD) isozymes were examined in cyclic AMP- or nerve growth factor (NGF)-treated PC12 cells. When the cells were incubated with dibutyryl cyclic AMP (dbcAMP), almost all the cells displayed prominent neurite outgrowth at 24 h. The neurites developed in NGF-treated cells at 24 h were shorter than those in the cells treated with dbcAMP. However, most of the NGF-treated cells extended long neurites at day 5. The rPLD1b mRNA increased within 6 h following dbcAMP treatment and maintained a high level up to 24 h. In contrast, the levels of rPLD1a and rPLD2 mRNAs were rather consistent throughout the time course examined. However, when the cells were treated with NGF, rPLD1a and rPLD1b mRNAs, but not rPLD2 mRNA, increased within 2 days and remained elevated up to 5 days. These results suggest the possible implication of PLD1 in PC12 cell differentiation.

Animals↗
PubMed1999

High-performance liquid chromatography study on effects of permanent wave, dye and decolorant treatments on methamphetamine and amphetamine in hair.

Black hairs that had been removed from a methamphetamine (MA) addict were treated with permanent wave, dye or decolorant liquids, and MA and amphetamine (AP) were quantified by a high-performance liquid chromatography/chemiluminescence detection method. The concentrations of MA and AP in the hair decreased significantly in all cases. Both MA and AP were stable in the permanent wave treatments, but not stable in the dye or decolorant treatments. As possible reasons for the decrease, the elution of MA and AP from hair in the permanent wave treatment, and the degradation of MA and AP in the dye or decolorant treatments might be considered. These results suggested that treatments of hair with permanent wave, dye or decolorant liquids interfered with determination of MA and AP in hair.

Adult↗
PubMed1999

A new orally active antitumor 1R,2R-cyclohexanediamine-platinum(IV) complex: trans-(n-valerato)chloro(1R,2R-cyclohexanediamine) (oxalato)platinum(IV).

PURPOSE: The authors have previously reported that trans-bis(n-valerato)(1R,2R-cyclohexanediamine) (oxalato)platinum(IV) (C5-OHP), an oxaliplatin derivative, is an orally active antitumor agent in an intraperitoneal (i.p.) L1210 murine leukemia model. In this study, several oxaliplatin derivatives of the general formula trans-(carboxylato)chloro(1R,2R-cyclohexanediamine)(oxala to)platinum(IV) were synthesized in order to find new derivatives with greater oral activity than C5-OHP in a clinically predictive tumor model. In the formula, the carboxylate and chloride ligands are situated in axial positions. METHOD: Four complexes with the axial carboxylate ligands n-butyrate, n-valerate, n-caproate or n-heptanoate were synthesized and designated C4-OHP-Cl, C5-OHP-Cl, C6-OHP-Cl and C7-OHP-Cl, respectively. The oral antitumor activity of the complexes was evaluated against the murine reticulosarcoma M5076 implanted subcutaneoulsy (s.c.) in to male BDF1 mice. The complexes were administered orally daily for 5 days in two cycles initiated on days 5 and 12 postimplantation. The physicochemical properties were examined by measuring the concentrations of the complexes in test solutions at intervals by HPLC. The pharmacokinetic behaviors of C5-OHP-Cl, C6-OHP-Cl and C5-OHP following a single oral administration were studied in non-tumor-bearing male BDFl mice. RESULTS: Of the complexes synthesized in this study, C5-OHP-Cl, which exhibited high activity in the i.p. L1210 model, was found to be orally active in the s.c. M5076 model while C5-OHP was not. The in vitro reduction of the complexes by ascorbate was much more rapid than that of C5-OHP, while the complexes were more stable than C5-OHP in HCl-acidic and alkaline solutions. Pharmacokinetic study showed that Cmax and AUC0 24h values of plasma total and filterable platinum of C5-OHP-Cl were four to six times greater than those of C5-OHP, indicating that C5-OHP-Cl was absorbed more than C5-OHP. CONCLUSION: C5-OHP-Cl was found to be a superior 1-OHP derivative C5-OHP, exhibiting significant oral antitumor activity in the s.c. M5076 model. The enhanced activity of C5-OHP-Cl was considered to be due in part to increased susceptibility to reduction and increased gastrointestinal absorption. C5-OHP-Cl is a suitable candidate for further study as an oral cancer chemotherapy agent.

Administration, Oral↗
PubMed1999

Role of hemolysis in potassium release by iodinated contrast medium.

It has been demonstrated that an iodinated contrast medium (CM) causes release of potassium into blood vessel lumina, resulting in an increase in serum potassium. The purpose of the present study was to assess whether this potassium release is due to hemolysis. Fresh human blood was mixed in vitro with CM at a ratio of 10:2. Potassium release rates were determined, and serum haptoglobin and free hemoglobin were measured after 30 min of exposure to CM. To compare the potassium release curve between CM exposure and true hemolysis induced by distilled water, fresh human blood was also mixed with distilled water. The level of serum haptoglobin decreased due to hemodilution. Changes in haptoglobin were not correlated with potassium release rates. The serum free hemoglobin level did not increase significantly, and there was no correlation between changes in the free hemoglobin level and the rate of potassium release. Hemolysis caused by water occurred instantaneously, whereas potassium release caused by CM was a slow response, which was linearly correlated with exposure time. Potassium release from blood cannot be explained by hemolysis.

Aged↗