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Biomedical subjects

K Asano

Publications and source records attributed to K Asano.

At least 199 records · Page 11Linked to original sources
PubMed1996

Cardiac adrenergic receptor effects of carvedilol.

Carvedilol is an adrenoceptor antagonist which modulates the activity not only of beta 1 and beta 2 but also of alpha 1 adrenergic receptors present on the cell surface membrane of the human cardiac myocyte. In the heart, carvedilol has approximately 7 times higher potency for beta 1 and beta 2 adrenoceptors, but in the doses 50-100 mg . day-1 used in clinical practice, it is essentially non-selective. In human myocardial preparations and in cultured heart cells, carvedilol has no intrinsic sympathomimetic activity but is able to identify high affinity agonist-binding receptors whose pharmacological signature is reduction in binding by incubation with guanine nucleotides (guanine nucleotide-modulatable binding). This property is more prominent for the human beta 2 than for the beta 1 adrenoceptor. The property of gaunine nucleotide-modulatable binding for carvedilol and structurally related bucindolol correlates with their ability to directly down-regulate beta 1-like receptors present in cultured chick myocytes, and with a lack of reversal of down-regulation of cardiac beta-receptors in patients with heart failure. Carvedilol does not exhibit high levels of inverse agonist activity, which may contribute to its good tolerability in subjects with heart failure. These data indicate that carvedilol produces a high degree of adrenergic receptor blockade in the failing human heart, and does not re-sensitize the beta-receptor pathway to stimulation by adrenergic agonists.

Adrenergic beta-Antagonists↗
PubMed1996

Prostaglandin G/H synthase-2 is the constitutive and dominant isoform in cultured human lung epithelial cells.

Two isoforms of prostaglandin G/H synthase (PGHS; prostaglandin endoperoxide synthase, cyclooxygenase) have been identified; PGHS-1 is expressed constitutively in most tissues, whereas PGHS-2 is thought to be induced by various proinflammatory cytokines and growth factors. In this study, we determined which isoform of PGHS mRNA, protein, and activity was present constitutively in A549 (a human lung adenocarcinoma cell line) and in untransformed (normal human bronchial epithelial or NHBE) and transformed (16HBE4o-) human bronchial epithelial cells. Two PGHS-2-specific inhibitors, NS-398 and L-745, 337, blocked the release of prostaglandin E2 from A549 cells with mean inhibitory concentrations of 5 and 18 nM, respectively, but did not inhibit its release from human bronchial smooth muscle cells (BSMC) at a concentration of 10 microM. Northern and immunoblot analysis demonstrated that BSMC expressed PGHS-1 mRNA and protein constitutively, whereas epithelial cells expressed PGHS-2 mRNA and protein constitutively with either undetectable (A549, 16HBE4o-) or very low levels (NHBE) of PGHS-1. We conclude that PGHS-2 is the dominant PGHS isoform in unstimulated and stimulated lung epithelial cells in culture.

Base Sequence↗
PubMed1996

Cytokine concentrations in sputum of asthmatic patients.

To examine whether levels of inflammatory cytokines and eosinophil cationic protein (ECP) in the sputum reflect the severity of bronchial asthma, we measured their levels in the sputum of symptomatic and asymptomatic asthmatics. Interleukin (IL)-1 beta, IL-5, IL-6, IL-8, RANTES, tumor necrosis factor-alpha and ECP concentrations in the sputum of symptomatic patients were significantly higher than in asymptomatic subjects. These findings suggest that these inflammatory cytokines are involved in the exacerbation of asthma.

Adult↗
PubMed1996

Modulation of hypoxic pulmonary vasoconstriction by antioxidant enzymes in red blood cells.

To determine whether antioxidant mechanisms within red blood cells (RBCs) significantly contribute to preserving hypoxic pulmonary vasoconstriction (HPV) in both the absence and the presence of oxidative stress, we investigated HPV changes in isolated rabbit lungs perfused with solutions containing RBCs treated with various inhibitors of superoxide dismutase (SOD), anion channels, catalase (CAT), or glutathione peroxidase (GSH-Px). Perfusion was maintained at a constant flow rate of 70 ml/min, and lung temperature at 37 to 38 degrees C. Hematocrit was adjusted to 7%. In the absence of overt oxidative stress, HPV was significantly enhanced in the perfusate containing control RBCs (untreated RBCs) as compared with that in Krebs-Henseleit buffer. Inhibition of SOD, CAT, and GSH-Px within RBCs, as well as anion channels located on the RBC membrane, had little influence on HPV. Neither exogenous SOD nor CAT altered HPV. In the presence of high levels of reactive oxygen species (ROS), generated by addition of xanthine (100 microM) and xanthine oxidase (10 mU/ml) to the reservoir, HPV was considerably suppressed in the perfusate containing only buffer but was restored in the perfusate with control RBCs. Inhibition of CAT or GSH-Px in RBCs preserved the HPV, whereas inhibition of SOD or anion channels failed to preserve HPV obtained during exposure to high ROS levels. Addition of exogenous SOD, but not CAT, to the perfusate containing RBCs in which endogenous SOD had been inhibited restored HPV under high ROS conditions. In conclusion, (1) although RBCs augment HPV in the absence of ROS, this finding is not attributable to the antioxidants in RBCs. (2) RBCs restore HPV upon exposure to high ROS. This finding may well be explained by antioxidant mechanisms operating within RBCs, especially those of endogenous SOD.

Animals↗
PubMed1996

Effect of endurance training under hypoxic condition on oxidative enzyme activity in rat skeletal muscle.

The adaptive response of oxidative enzyme activity in the skeletal muscle to training in normoxic and in normobaric hypoxic training was studied. Forty male Wistar rats were divided into 4 groups: normoxia + sedentary (NS, n = 10); hypoxia + sedentary (HS, n = 10); normoxia + training (NT, n = 10); and hypoxia + training (HT, n = 10). Rats in the NT group ran on a treadmill for 30 min a day at 20-30 m.min-1, 4 days a week for 10 weeks in normoxia. Rats in the HT group performed the same training protocol as NT in an ambient FIO2 decreased to 12%. HS rats were exposed to hypoxia in the same degree, duration and frequency as HT without exercise. After the training period, the soleus and the plantaris muscles were removed, and the activities of mitochondrial enzymes, malate dehydrogenase (MDH) and 3-hydroxyacyl-CoA dehydrogenase (HAD) were measured by a spectrophotometer. The normoxic training did not increase MDH or HAD activities, in either the soleus or the plantaris. This absence of change in mitochondrial enzyme activities is considered to be the results of inadequate stimulus of training, including a relatively low amount of exercise. On the other hand, the hypoxic training enhanced the MDH activity in the soleus by 17.5% compared with NS (P < 0.01) and by 20.5% compared with HS (P < 0.01). Also in the plantaris, the MDH activity in HT was higher than that in HS (15.7%, P < 0.05). These findings suggest that even moderate training by which enzyme activity is not increased under normoxic conditions can enhance the oxidative capacity in the skeletal muscle when the training is performed in a hypoxic environment.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1996

Changes in aerobic capacity and coronary risk factors during long-term exercise training in women with ischemic heart disease: a 36-month follow-up.

We evaluated the time course of alteration in aerobic capacity and coronary risk factors associated with a 36-month exercise program in women with ischemic heart disease (IHD). Twenty-one patients participated in supervised exercise and home-based exercise programs for 36 months. However, of all patients, 11 patients completed the entire program. Oxygen uptake corresponding to lactate threshold (VO2LT), peak oxygen uptake (VO2peak), percent of body fat (%BF), systolic (BPs) and diastolic (BPd) blood pressure, total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC) and triglycerides (TG) were assessed before and 4, 8, 12, 24, and 36 months after exercise. The intensity of exercise was set at individually determined LT, i.e., 60 to 70% VO2peak. The daily amount of exercise during 36 months averaged 24.0 +/- 11.4 minutes per day. During the course of exercise program, VO2LT, VO2peak, BPs, BPd, and TG improved significantly at month 4. Although %BF decreased significantly at month 8 to 12, it tended to return to the initial level at month 36. On the other hand, a significant increase in HDLC was found at month 24 and improved state of HDLC remained unchanged thereafter. No changes were found in TC and LDLC. These results suggest that most of the beneficial effects of exercise on aerobic capacity and coronary risk factors in women with IHD are obtained within 4-8 months, with some further improvement seen with continued exercise up to 24 months.

Blood Pressure↗
PubMed1996

[Determination of 5-FU tissue concentrations after oral UFT administration in tumors of the head and neck].

We determined the 5-FU concentrations in the tumor tissue, normal tissue surrounding the tumor, metastatic lymph nodes, normal lymph nodes, and serum after oral UFT administration to 26 patients with primary squamous cell carcinoma in the head and neck. The 5-FU concentration was mean 0.20 +/- 0.13 micrograms/g in the tumor tissue and mean 0.14 +/- 0.08 micrograms/g in the metastatic lymph nodes. The 5-FU concentrations in the tumor tissue and metastatic lymph nodes were significantly higher than in the corresponding normal tissue surrounding the tumor and normal lymph nodes. In addition, the 5-FU concentration was significantly higher in the tumor tissue than in the metastatic lymph nodes. No significant differences were observed in the 5-FU concentration according to the sites of the primary tumor. However, the difference in the 5-FU concentration between the tumor and normal tissues was smaller in tongue cancer than in pharyngeal cancer.

Administration, Oral↗
PubMed1996

[The relationship between cell proliferation activity and secretory activity in pituitary adenoma--a review of 63 cases].

Determination of the cell proliferation activity of neoplasm is useful in making a prognosis. Immunohistochemical detection using MIB-1 monoclonal antibody has recently allowed us to assess tumor cell proliferation easily, because it can be performed on paraffin-embedded specimens and the results have been demonstrated to be positively correlated with the results of PCNA staining. In this study, surgical specimens of 63 pituitary adenomas were examined by immunohistochemical staining with MIB-1 monoclonal antibody. Twenty-nine cases were non-functioning pituitary adenomas, 20 were prolactin (PRL)-producing pituitary adenomas, and 14 were growth hormone (GH)-producing pituitary adenomas. The MIB-1 positive rates of the pituitary adenomas ranged from 0% to 6.46%. In the non-functioning pituitary adenomas, the MIB-1 positive rates ranged from 0% to 4.55% (mean : 0.76%), in the PRL-producing pituitary adenomas the MIB-1 positive rates ranged 0% to 6.46% (mean : 0.91%), and in the GH-producing pituitary adenomas the MIB-1 positive rates ranged 0% to 1.28% (mean: 0.58%). There were no significant differences between these values according to the results of the Wilcoxon signed-rank test. Although the size of the non-functioning pituitary adenomas was not correlated with their MIB-1 positive rate, tumor size was closely correlated with the interval between the onset of the initial symptoms and the date of surgery. In the PRL-producing pituitary adenomas, the MIB-1 positive rate was not correlated with serum PRL levels as an index of secretory activity, but was correlated with the PRL staining positive rate. Preoperative bromocriptine therapy proved effective in reducing tumor size and serum PRL levels, but had no effect on the MIB-1 positive rate. In the GH-producing pituitary adenomas, the MIB-1 positive rate was not correlated with serum GH levels as an index of secretory activity, but was closely correlated with the GH staining positive rate. All three groups included both invasive and noninvasive tumor types, but there were no close statistical correlations between the three tumor types.

Adenoma↗
PubMed1996

[A case of one stage operation for primary lung cancer and abdominal aortic aneurysm].

A 75-year-old male patient of primary lung cancer associated with abdominal aortic aneurysm was operated successfully in one stage. Right S2, S3 lung cancer was resected first and then aortic aneurysm was replaced with a Dacron graft. Both disease should be operated upon as early as possible. Low dose heparin usage did not disturb the operation. This case is the third reported case of one stage operation in Japan.

Adenocarcinoma↗
PubMed1996

[A case of invasive thymoma made resectable by preoperative chemotherapy].

A 25-year-old male patient of invasive thymoma was referred to our institute on March'95. He had night coughs and on the annual chest X ray exam a large tumor was found in antero-superior mediastinum. At first his tumor was too large to be resected and left brachiocephalic vein was completely occluded. By needle biopsy it was proved to be thymoma, therefore, preoperative chemotherapy was planned. The tumor responded well to the two courses of ADOC (ADM, CDDP, VCR, CAP) therapy and the tumor seemed to become resectable. In June operation was performed and the tumor was resected completely. It appears that in case of stage Ill invasive thymoma, preoperative chemotherapy is one of the choices although it seems unresectable.

Adult↗
PubMed1996

[A clinico-pathological study of cystic spinal Schwannomas].

It is not rare for a spinal Schwannoma to have cystic formations, but there are various opinions about the mechanism. Since the installation of MRI in our institution in 1989, we have experienced 4 cases of cystic spinal Schwannoma. The diagnosis of such lesions was based on identifying cystic formations histopathologically. Among these cases, tiny hemorrhages were noted microscopically in three of them along with hemosiderin depositions and phagocytes containing hemosiderin. Besides, there are also a lot of sinusoidal vessels with thin endothelium. Perhaps in these three cases, it is the tiny hemorrhages that resulted in degenerative changes which in turn caused the formation of microcysts. But in addition to the above findings, a lot of hyalinized vessels were also demonstrated in the angiomatous components of two cases. Therefore, it is also possible that the microcyst formation is secondary to the degenerative changes caused by ischemia within the tumors. On the other hand, in the only case without hemorrhage, neither phagocytes containing hemosiderin nor abnormal sinusoidal vessels could be found. In stead, a lot of clear foamy cells with positive lipid staining were seen. There may be some factors underlying the xanthomatous change of these tumors that cause their vacuolar formation from degenerated of the foamy cells. It is possible that all three factors mentioned above may act alone or in combination to contribute to the formation of cysts. At its late stage, a spinal Schwannoma may have various findings which can not be classified into either Antoni A or Antoni B type. In conclusion, a spinal Schwannoma can occasionally have cystic formations. Its mechanisms can be a hemorrhagic or an ischemic process occurring within the tumor.

Adult↗
PubMed1996

[Clinical effects of beni-koji in mild essential hypertension--a multi-center double-blind comparison with placebo].

Antihypertensive effects of beni-koji were studied using 29 outpatients with mild hypertension in a placebo-controlled double-blind comparative fashion. After a 4-week vehicle (apple juice) run-in period, 13 patients were assigned to receive beni-koji aqueous extracts containing juice once daily (27 g of beni-koji eq. per day) for 8 weeks and 16 were assigned to vehicle. Two patients assigned to the vehicle group did not complete the study. In addition to casual blood pressure, 24-hr non-invasive ambulatory blood pressure (ABP) was monitored in 6 patients given the beni-koji drink and 5 patients given the vehicle. 1) In the beni-koji group, both casual systolic and diastolic pressure decreased significantly during the treatment period (from 150 +/- 10/96 +/- 6 mmHg to 140 +/- 10/89 +/- 10 mmHg, p < 0.01). The averages of the 24-hr blood pressure recorded in ABP (24-BP) also significantly decreased (from 141 +/- 17/95 +/- 13 mmHg to 132 +/- 21/86 +/- 10 mmHg, p < 0.05) when compared with those of the control period. Casual pressure normalized (less than 140/90 mmHg) in 4 patients who received beni-koji. Circadian variation of the blood pressure by ABP showed a significant decrease during the daytime. 2) In the vehicle group, casual systolic pressure did not change significantly (from 155 +/- 8 mmHg to 151 +/- 12 mmHg), but diastolic pressure decreased significantly (98 +/- 7 mmHg to 93 +/- 6 mmHg). Casual blood pressure did not normalize in any of the patients and 24-BP did not change significantly. 3) Summative evaluation of safety showed that no problems appeared in the beni-koji group. In conclusion, beni-koji appears to be an effective and safe food material for mild essential hypertension. The mechanism of the antihypertensive effect of beni-koji still remains to be investigated.

Antihypertensive Agents↗
PubMed1995

Tumorigenicity and gene amplification potentials of cyclin D1-overexpressing NIH3T3 cells.

Cyclin D1 is a key regulator of the G1-S transition in cell cycle, and its gene is amplified and overexpressed in many cancers. To address the gene amplification potential of the cells in which the cyclin D1 gene expression is deregulated, we have established NIH3T3 clones with various levels of cyclin D1 transgene message. Those transfectants showed anchorage independent growth and tumorigenicity without in vitro morphological transformation. The degree of the transformed phenotype apparently correlated with the cyclin D1 expression level. Upon selection by N-(phosphonoacetyl)-L-aspartate (PALA), the cyclin D1-transfected NIH3T3 cells showed a higher ability to develop PALA-resistant colonies by amplifying the CAD gene, as compared to the parental NIH3T3 cells.

3T3 Cells↗
PubMed1995

An essential role of prostaglandin E on mouse mast cell induction.

We previously established a system for induction of mucosal-type mast cells from mouse spleen cells by long term culture without exogenous IL-3. FCS was important and was able to be divided into mast cell-inducible and non-mast cell-inducible sera. LPS contaminated in FCS was responsible for the mast cell induction. However, we unexpectedly found that both supernatants recovered from the cultures with mast cell-inducible and non-mast cell-inducible sera contained endogenous IL-3. Furthermore, addition of rIL-3 to the cultures with non-mast cell-inducible sera had no effect or induced only a small number of mast cells. This indicates that IL-3 alone is not enough for mast cell induction and that some inflammatory factor(s) induced by LPS is also essential. Prostaglandin E1 (PGE1) and PGE2 induced mast cells in a dose-dependent manner when added into the cultures. The activity of LPS for mast cell induction was inhibited by indomethacin. However, indomethacin failed to inhibit the mast cell induction by exogenous PGE. Exogenous PGE antagonized the indomethacin-induced inhibition of mast cell induction by LPS. Cholera toxin and dibutyryl cyclic AMP (cAMP) also induced mast cells. The A and B subunits of cholera toxin, PGF2 alpha, PGD2, and dibutyryl cGMP failed to induce mast cells. Furthermore, mast cell induction by PGE was dose-dependently suppressed by inhibitors for cAMP-dependent A kinase. The above results show that for mast cell induction, IL-3 needs the cooperation of PGE or other stimulants that can elevate the production of the second messenger cAMP in mast cell precursors.

Animals↗
PubMed1995

[A rare case of a diabetic patient with small cell lung cancer, initially diagnosed as pyogenic vertebral osteomyelitis].

A rare case of a patient with non-insulin-dependent diabetes mellitus (NIDDM) with small cell lung cancer, initially diagnosed as pyogenic vertebral osteomyelitis, was reported. A 40-year-old male patient was diagnosed with NIDDM about 3 years earlier, but he did not receive any treatment. Then, a two-month history of high fever, persistent cough and back pain developed. Chest X-ray film showed a lung infiltrate with a small cavity in the upper portion of the left lung. Computed tomography and magnetic resonance imaging of the chest revealed a tumor mass shadow with osteoclasia along the bodies of the 6th and 7th thoracic vertebral bone. Staphylococcus aureus infection was confirmed by arterial blood culture. Administration of antibiotics resulted in the disappearance of the left lung infiltrate and a slight reduction of the tumor mass in the thoracic vertebral bone, suggesting pyogenic vertebral osteomyelitis as an unusual complication of NIDDM. However, as the tumor mass still remained, needle biopsy for the mass lesion was performed, resulting in the diagnosis of metastasis of small cell carcinoma from the left lung. Gene aberration in this lung disease has been reported recently, and its correlation with NIDDM which may also be induced by genetic abnormality is an interesting question that remains to be resolved.

Adult↗
PubMed1995

The function of 5-HT3 receptors on colonic transit in rats.

The function of serotonin (5-HT)3 receptors on colonic transit was investigated in unanesthetized rats. The colonic transit was accelerated by 5-HT (10 mg/kg, s.c.), 2-methyl-5-HT (30 mg/kg, s.c.), neostigmine (0.03-0.1 mg/kg, s.c.), corticotropin releasing factor (CRF; 1 microgram intracerebroventricular administration) and restraint stress (for 45 minutes). A potent and selective 5-HT3 receptor antagonist, azasetron (+/-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro- 4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide monohydrochloride ; 0.01-10 mg/kg, p.o. inhibited the 5-HT-, CRF- and stress-accelerated colonic transit in a dose-dependent manner. Ondansetron (10 mg/kg, p.o.) and granisetron (1 mg/kg, p.o) also inhibited the stress-accelerated colonic transit, but azasetron was more effective than these two drugs. Atropine methylbromide (0.1 mg/kg, s.c.) and tetrodotoxin (0.01 mg/kg, s.c.) inhibited the accelerated colonic transit under stress conditions, but methysergide (10 mg/kg, s.c.), SDZ205-557 (10 mg/kg, s.c.), domperidone (30 mg/kg, p.o.), trimebutine (300 mg/kg, p.o.), did not. Azasetron (10 micrograms) administered intracerebroventricularly did not inhibit the stress-induced acceleration. These results suggest that endogenous 5-HT which is released through stress accelerates the colonic transit via the 5-HT3 receptors and finally a cholinergic mechanism. It is considered that azasetron inhibits colonic transit particularly under stress conditions through the blockade of the peripheral 5-HT3 receptors. Azasetron may improve bowel function in stress-related colonic dysfunction like irritable bowel syndrome.

Animals↗
PubMed1995

A petrous bone destructive acoustic neurinoma: a tumor of far-lateral origin?

We report a case of an acoustic neurinoma that recurred more than 11 years after "total" tumor removal through the posterior cranial fossa. Recurrent tumor had obliterated the petrous bone, filled the middle ear, and was visible grossly at the external auditory meatus. The unique behavior of this tumor implied that the site of origin was within the labyrinth, beyond the fundus of the internal auditory canal and far lateral to the usual site of acoustic neurinoma origin. We offer an hypothesis as to why these tumors occasionally recur, even after clinical "total" removal.

Brain Stem↗