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Biomedical subjects

K Koga

Publications and source records attributed to K Koga.

At least 163 records · Page 9Linked to original sources
PubMed1995

Differential effects of OPC-18790, amrinone and dobutamine on cardiac function and energy metabolism in the guinea-pig isolated ischaemic heart.

1. The effects of OPC-18790, a novel positive inotropic agent, on cardiac function and myocardial energy metabolism in the guinea-pig isolated heart with ischaemia were studied by 31P-magnetic resonance spectroscopy (MRS) and compared with those of amrinone and dobutamine. 2. Cardiac ischaemia was induced by intracoronary infusion of 15 microns microspheres to reduce coronary perfusion flow (CPF) by 50%. Microsphere embolisation caused a 40% decrease in left ventricular systolic pressure (LVSP), cardiac contractility measured by peak of ventricular pressure development (LVdP/dt) and slightly reduced heart rate. There was also a decrease in ATP and creatine phosphate (PCr) by 20%, an increase in inorganic phosphate (Pi) by 25% and an acidic shift of intracellular pH in the ischaemic heart. 3. In the ischaemic heart, OPC-18790, amrinone and dobutamine were applied at concentrations which increased LVdP/dt by about 60%. These compounds increased LVP by 15% to 30% and increased CPF by about 10%. Amrinone and dobutamine but not OPC-18790 increased heart rate. When these drugs produced the haemodynamic changes described above, amrinone and dobutamine reduced ATP and PCr, increased Pi and produced further intracellular acidosis, whereas, OPC-18790 did not change these parameters. 4. Cardiac pacing at 285 beats min-1 produced decreases in LVP, LVdP/dt and CPF by about 30%, 20%, 5%, respectively and an increase in Pi, decreases in PCr and ATP, and intracellular acidosis. 5. These results suggest that degradation of high energy phosphate compounds closely relates to increase in heart rate in the ischaemic heart. Positive inotropic agents without chronotropic action seem to be beneficial in support of the ischaemic heart.

Adenosine Triphosphate↗
PubMed1995

Antitumour effects and pharmacokinetics of combination of vinblastine with a staurosporine derivative, NA-382, in P388/ADR-bearing mice.

The effects of a staurosporine derivative, N-ethoxycarbonyl-7-oxostaurosporine (NA-382), on the pharmacokinetics of vinblastine were evaluated, compared with those of verapamil, in multidrug-resistant P388/ADR-bearing mice. At first, the in-vitro experiments indicated that NA-382 permeated into the cells better and were more effective in combined cytotoxicity with vinblastine and on accumulation of vinblastine than with verapamil in P388/ADR cells. In combined intraperitoneal injection with vinblastine (200 micrograms kg-1) into P388/ADR-bearing mice, NA-382 in a suspension form (10 mg kg-1) prolonged the life-span of the mice near to that of P388/S-bearing mice treated with vinblastine alone, but verapamil even at the maximum tolerated dosage (30 mg kg-1) barely affected the in-vivo antitumour effect of vinblastine. When simultaneously administered with vinblastine to P388/ADR-bearing mice, NA-382 maintained significantly higher vinblastine levels in the tumour cells for 24 h and gave a larger area under the time-intracellular vinblastine concentration curve (0 to 24 h) than those receiving vinblastine alone, with long retention of the agent in ascitic fluid. Verapamil increased the cellular vinblastine content for only 6 h, accompanying a rapid elimination of the agent from the ascitic fluid. This study indicates that NA-382 is more effective against multidrug-resistance than verapamil, and its suspension is also advantageous for cancer chemotherapy of multidrug-resistant tumours.

Alkaloids↗
PubMed1995

Transient adenosine infusion before ischemia and reperfusion protects against metabolic damage in pig hearts.

We investigated whether transient adenosine (Ado) infusion before ischemia had the same effect on myocardial metabolism and function as ischemic preconditioning (IP). The control (C) group underwent 15 min of coronary artery occlusion followed by 120 min of reperfusion. The Ado group received a 15-min infusion of Ado (200 micrograms.kg-1.min-1) into the left atrium starting 20 min before ischemia. IP was elicited by two cycles of 5-min ischemia and 5-min reperfusion. In the area at risk, tissue levels of ATP, creatine phosphate (CP), and intracellular pH (pHi) were serially measured by 31P-nuclear magnetic resonance spectroscopy in 10 pigs from each group, and percent segment shortening (%SS) was measured in 7 pigs from each group. ATP and pHi were preserved after 15 min of ischemia in both Ado and IP groups [ATP = 64 +/- 7, 76 +/- 6, and 74 +/- 9% of baseline; pHi = 6.35 +/- 0.19, 6.54 +/- 0.11, and 6.64 +/- 0.11 in C, Ado, and IP groups, respectively (P < 0.05, Ado and IP vs. C)]. During reperfusion, ATP was restored progressively in both groups [71 +/- 7, 90 +/- 8, and 91 +/- 9% of baseline at 120 min of reperfusion in C, Ado, and IP groups, respectively (P < 0.05, Ado and IP vs. C)]. However, in contrast to the IP group, CP was not preserved during 15-min ischemia nor did it show persistent overshoot during reperfusion in the Ado group. There were no significant differences in %SS during ischemia and reperfusion among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1995

Effects of OPC-18790, a new positive inotropic agent, on energetics in the ischaemic canine heart: a 31P-MRS study.

OBJECTIVE: Effects of OPC-18790, a novel positive inotropic agent, on cardiohaemodynamics and cardiac energetics were assessed simultaneously in dogs with cardiac ischaemia using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) and compared with those of amrinone, a pure cGMP-inhibited PDE inhibitor. METHODS: Cardiac ischaemia was produced by partial stenosis of the coronary artery. Dogs with cardiac ischaemia were instrumented for the determination of regional coronary blood flow (non-radioactive coloured microsphere method), regional contractile function (sonomicrometry), and haemodynamics. Myocardial phosphate compounds were measured simultaneously by 31P-MRS. RESULTS: Coronary stenosis produced regional dyskinesis, a slight decrease in cardiac output (CO), intracellular acidosis, an increase in the inorganic phosphate (Pi)/creatine phosphate (PCr) ratio concomitantly with a decrease in regional coronary blood flow (CBF) in the ischaemic region. OPC-18790 dose-dependently produced an increase in contractility (measured by peak LVdP/dt) and CO, with only slight changes in heart rate (HR) and mean blood pressure (mBP). OPC-18790 did not change regional dyskinesis, but improved the Pi/PCr ratio at the high dose compared with ischaemic values (before drug administration). Amrinone produced an increase in CO comparable to that of OPC-18790; however, the increase in peak LVdP/dt was smaller while the increase in HR and decrease in mBP were larger than those seen with OPC-18790. Amrinone worsened the Pi/PCr ratio and intracellular acidosis only at the high dose. CONCLUSION: These observed differences in energy metabolism between OPC-18790 and amrinone at the high dose may be due to the ability of OPC-18790 to increase CBF in the ischaemic region and which may attributed to its differing effect on overall haemodynamics. Thus, OPC-18790 may be useful in the management of ischaemic heart failure.

Amrinone↗
PubMed1994

Isolation and characterization of cDNA and genomic promoter region for a heat shock protein 30 from Aspergillus nidulans.

A cDNA encoding for a heat shock protein 30 (HSP30) of Aspergillus nidulans and the promoter region of its gene were analyzed for their primary structures. The promoter region had no heat shock element but possessed three inverted repeat sequences. Northern blot hybridization indicated that the expression of the HSP30 gene was high at a normal temperature and was slightly accelerated at elevated temperatures in A. nidulans cells. Although the deduced amino acid sequence of the A. nidulans HSP30 had a domain highly conserved among other small HSPs from different species, it showed a sequence homology of only 42% even in comparison with the most closely related molecular species, Neurospora crassa HSP30. These findings suggest that the present HSP30 belongs to a novel subfamily of low-molecular-weight HSPs.

Amino Acid Sequence↗
PubMed1994

Ketamine suppresses endotoxin-induced tumor necrosis factor alpha production in mice.

BACKGROUND: The cytokines play important roles in the pathophysiologic alterations associated with sepsis, but there are no reports about the effect of anesthetics on their production. Therefore, the authors examined the effect of ketamine on lipopolysaccharide (LPS)-induced and calcium ionophore A23187-induced tumor necrosis factor alpha (TNF-alpha) production in thioglycolate (TGC)-elicited peritoneal macrophages (MPs) in ddY mice. METHODS: Ketamine was added to TGC-elicited MPs at various times after the stimulation with LPS or A23187. After the MPs were stimulated by LPS or A23187 and incubated, TNF-alpha activities in the supernatant of MPs were determined by an L929 cytotoxic assay. In vivo, the ddY mice were injected intraperitoneally with TGC. Four days later, they were injected subcutaneously with ketamine and then injected intravenously with LPS. Two hours after the LPS challenge, TNF-alpha activities of the sera were determined. RESULTS: Ketamine suppressed both LPS-induced and A23187-induced TNF-alpha production in a dose-dependent manner. The simultaneous addition of ketamine to LPS-stimulated and A23187-stimulated MPs resulted in a 50% inhibition of TNF-alpha production at 20 micrograms/ml and 12.5 micrograms/ml, respectively. Ketamine also caused a significant suppression of TNF-alpha production even when added to the MPs 2 h after the LPS challenge. There was a significant decrease in A23187-induced TNF-alpha production in TGC-elicited MPs in a calcium-depleted medium when compared with that in a calcium-containing medium. Conversely, LPS-induced TNF-alpha production did not cause such a result. In addition, ketamine could suppress LPS-induced TNF-alpha production in TGC-pretreated mice in vivo. CONCLUSIONS: Ketamine suppresses LPS-induced TNF-alpha production in both TGC-elicited MPs and TGC-pretreated mice.

Animals↗
PubMed1994

Thymic carcinoma: proposal for pathological TNM and staging.

Recently, Yamakawa et al. following Masaoka's clinical staging of thymic epithelial tumors, proposed a TNM classification and staging system for thymic epithelial tumors including thymoma and thymic carcinoma. The present authors consider that division of thymomas into circumscribed types (either encapsulated or non-encapsulated but confined to within the thymus) and those invasive to adjacent organs or structures is sufficiently practical, and that a staging system is applicable to thymic carcinoma, carcinoid tumors and germ cell tumors of the anterior mediastinum, which are more malignant than thymoma. Therefore, the utility of the Yamakawa/Masaoka TNM and staging system was evaluated and a modification proposed based on experience with 16 thymic carcinomas. Although there were no cases at stage II, the survival curves obtained using the proposed modified system were more clearly separated between stages I and III or IV and between stages III and IV than the curves obtained using the Yamakawa/Masaoka system. However, the differences were not significant because of the small number of cases included. A statistically significant difference was noted between the survival curves for patients who underwent complete and incomplete surgical resection of the tumor. The utility of this proposed TNM and staging system must be evaluated by other investigators, since no cases of small cell carcinoma, lymphoepithelioma-like carcinoma, sarcomatoid carcinoma and clear cell carcinoma were included in this series, all of which are considered to have high-grade histology. An evaluation of carcinoid tumor and germ cell tumor of the anterior mediastinum must also be made.

Adult↗
PubMed1994

A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma.

A clinicopathological study of surgically resected thymomas was performed using Masaoka's staging and modified Masaoka's staging systems, and the utility of these two staging systems was compared. The modification enabled adjustment for the disproportion in the number of cases between Stage I and Stage II. Analysis of survival rates, according to the tumor stage, indicated that the old classification should be reappraised, that is, division into non-invasive and invasive thymomas, although staging may contribute to the indication for postoperative radiotherapy, especially for Stage II disease. Analysis of the cases showed a wide spectrum of aggressiveness, varying from cases showing slow progression with a relatively favorable prognosis, such as the spindle cell type, to cases with rapid progression leading to tumor death in a relatively short time, such as the epithelial cell predominant and polygonal cell type. The pathological stage at the time of first surgical resection would reflect the degree of aggressiveness of thymoma in many instances. Therefore, not only staging the tumor extent but also grading of its aggressiveness are needed in order to predict the prognosis of patients with thymoma. For the latter, histology and cytopathology are helpful.

Adolescent↗
PubMed1994

Effect of peripheral benzodiazepine receptor ligands on lipopolysaccharide-induced tumor necrosis factor activity in thioglycolate-treated mice.

To investigate the effect of peripheral and central benzodiazepine receptor ligands on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) activity in mouse macrophages, three types of ligands, 4'-chlorodiazepam (pure peripheral), midazolam (mixed), and clonazepam (pure central), were compared. Midazolam and 4'-chlorodiazepam significantly suppressed LPS (1-microgram/ml)-induced TNF activity in thioglycolate-elicited mouse macrophages. In every concentration examined (0.001 to 100 microM), 4'-chlorodiazepam was the most effective agent, clonazepam was the least effective agent, and midazolam had an effect intermediate between those of the other two ligands. The peripheral benzodiazepine receptor ligands had a dose-dependent suppressive effect, and the 50% inhibitory concentrations were 0.01 microM for 4'-chlorodiazepam and 5 microM for midazolam. Concomitant use of PK 11195 (10 microM), an antagonist of the peripheral benzodiazepine receptor, reversed this suppressive effect with 4'-chlorodiazepam (10 microM) or midazolam (10 microM). PK 11195 showed this antagonistic effect in a dose-dependent manner. Intravenous 4'-chlorodiazepam (5 mg/kg of body weight) significantly suppressed LPS (100-micrograms)-induced TNF activity of sera (2 h postchallenge with LPS) from thioglycolate-treated mice. The present findings suggest that the peripheral benzodiazepine receptor plays an important role in modulating LPS-induced TNF activity in mouse macrophages.

Animals↗
PubMed1994

Choanal atresia and congenital pharyngeal stenosis.

From 1980 to 1992, 8 patients with choanal atresia were treated in our facility. The female to male ratio was 5:3. One patient, a girl, had unilateral osseous obstruction with membranous closure of the opposite naris while the other 7 had bilateral osseous obstruction. Seven of the 8 had other congenital anomalies, CHARGE association (2 cases), Apert's syndrome (1 case), meningocele and banded fingers (1 case), omphalocele (1 case), subdural hematoma (1 case), and nasal fistula (1 case). Of the 7 patients who underwent endonasal surgical repair, 3 (40%) experienced reclosure. The remaining one patient, whose obstruction was of the bilateral osseous type, was successfully operated on via a transpalatal approach. Surgical correction is particularly difficult in those with craniofacial abnormalities, e.g. Apert's syndrome and maxillary hypoplasia. We treated 5 congenital pharyneal stenosis cases (CPS). Our CPS cases were divided into Types 1, 2 and 3, the latter being a new type not previously reported on. We consider Type 3 to be the result of fetal tissue remnants. We performed uvula splitting surgery in 4 cases and obtained good results in 3.

Abnormalities, Multiple↗
PubMed1994

Idiopathic deafness or hearing loss of unknown etiology following discharge from the NICU.

The clinical course, treatment and respiratory management of 6 infants who developed profound hearing loss (n = 5) or high tone hearing loss (n = 1) some months after discharge from the NICU are presented. All 6 infants had congenital and/or perinatal diseases causing hypoxia, and all were treated with gentamycin. All were nearly normal at discharge but later rose to 80-90 dB, or 60 dB in the case with high tone hearing loss. The hearing impairment was thought to be due to hypoxia, in combination with medications and invasive procedures. Follow-up audiologic testing is recommended after NICU discharge.

Child, Preschool↗
PubMed1994

[Hearing loss following discharge from the NICU].

We experienced 10 pediatric cases born between November of 1988 and November of 1992, whose ABR were normal at the time of discharge from the NICU, who subsequently developed hearing impairment. These children underwent thorough evaluations and the causes of their hearing loss are discussed herein. All 10 were born at full term, birth weights ranged from 2500g to 3826g, and all had severe cardiovascular and/or pulmonary disorders. Eight of the 10 had persistent pulmonary hypertension of the newborn (PPHN). During the four year period in which these 10 infants were born, a total of 25 PPHN cases were diagnosed in our NICU, i.e. the rate of hearing loss in PPHN infants was 32% (8/25). All 10 infants were intubated and maintained on mechanical ventilation for an average of 30 days. Five cases also required high frequency oscillation and six received extracorporeal membrane oxygenation (ECMO). During the same time period there were only eight surviving ECMO cases such that the rate of hearing loss was 75% (6/8). All 10 were treated with an aminoglycoside, furosemide and a muscle relaxant. As These infants are at very high risk for hearing impairment, follow-up at 6 and 12 months of age is essential.

Evoked Potentials, Auditory, Brain Stem↗
PubMed1994

Ketamine suppresses tumor necrosis factor-alpha activity and mortality in carrageenan-sensitized endotoxin shock model.

We have reported that an intravenous anesthetic, ketamine, has a potent suppressive effect on lipopolysaccharide (LPS)-induced TNF-alpha production in vitro [Takenaka et al., Anesthesiology 80:402-408, 1994]. The purpose of the present study was to investigate the overall effects of ketamine on hemodynamics, serum TNF-alpha level, arterial blood gases (ABGs), blood glucose level, liver function, and lethality in carrageenan (CAR)-sensitized endotoxemic models. All animals were pretreated intraperitoneally with CAR (150 mg/kg) 16 hr before LPS stimulation. The control rats were injected LPS with 0.5 mg/kg intravenously (i.v.). The ketamine-treated rats were injected with 100 mg/kg of ketamine intramuscularly 30 min before LPS (0.5 mg/kg) i.v. injection, followed by an i.v. infusion at 0, 5, or 10 mg/kg/hr. Serum TNF-alpha, ABGs, blood glucose, and hematological studies were determined at 0, 2, and 6 hr after the LPS challenge. Serum hepatocellular enzyme levels were measured at 6 hr after the injection. In CAR-sensitized rats, serum TNF-alpha activity remarkably increased in accordance with the mild decrease of mean arterial pressure (MAP) at 2 hr after LPS stimulation. In addition, severe metabolic acidosis, hypoglycemia as well as severe hepatic injury were induced at 6 hr after the LPS challenge. By contrast, ketamine treatment significantly attenuated the decrease in MAP and LPS-induced TNF-alpha activity. Ketamine also significantly improved arterial oxygen tension (PaO2), metabolic acidosis and hypoglycemia, and attenuated endotoxin-induced hepatic injury in a dose-dependent fashion. In addition, ketamine treatment significantly improved LPS-induced lethality in CAR-sensitized mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1993

Preliminary report: suspicion of hearing-loss at age 0-1 years by TV viewing attitude.

To determine any difference of TV viewing attitude between normal and hearing-loss children, 14 normal and 8 sensory impaired infants/toddlers were observed separately in a playroom with a TV set showing a 12-min videotape. All children enjoyed TV and showed clear differences in TV viewing behavior between hearing-loss and auditory normal children. At the beginning of their favorite programs or changes in programs, normal infants/toddlers were quickly aware of the TV sound and turned toward the TV set, where as hearing-loss children remained unaware. Our observation proved the intact hearing of two clients who had not responded to regular infant auditory tests. Moreover, we surveyed 65 hearing-loss children. Only 21% of them began to watch TV at 0 year of age, 50% at 1 year. They did it apparently later than normal infants who began to watch TV mostly before 1 year of age in the Japanese general population. From fitting with a hearing aid, however, most of them began to enjoy TV, watch it longer, have their favorite programs (music, songs, etc.) and turn to face the TV whenever a favorite program began. This suggests hearing acuity is important to enjoy TV. Since TV is already familiar and attractive to most any children, it is a useful and sensitive tool for early detection of hearing-loss children at 6-18 months of age.

Child Behavior↗
PubMed1993

Comparative studies on the metabolism of new fluorinated pyrimidine drugs in the liver by in vivo 19F magnetic resonance spectroscopic observation.

1-Ethoxymethyl-5-fluorouracil (EM-FU) is a fluorinated pyrimidine derived from 5-FU, and 3-cyano-2,6-dihydroxypyridine (CNDP) is a chemical modulator which suppresses the catabolism of 5-FU by inhibiting dihydrouracil dehydrogenase in the liver. In this study, the metabolism of EM-FU and the suppression of 5-FU catabolism by CNDP were observed by in vivo 19F magnetic resonance spectroscopy in comparison with other similar drugs, because it is considered that the most effective mode of therapy using 5-FU is to suppress the catabolism of 5-FU in the liver and so to maintain for longer an effective blood level of 5-FU. The metabolism of EM-FU was very slow and the production of fluoro-beta-alanine was very low as compared to the case of tegafur. The catabolic suppression by CNDP was much stronger than that of uracil. Therefore co-administration of EM-FU and CNDP should suppress catabolism and maintain an effective blood level of 5-FU for a long period of time.

Alanine↗
PubMed1993

An antagonist of platelet-activating factor suppresses endotoxin-induced tumor necrosis factor and mortality in mice pretreated with carrageenan.

We found that carrageenan (CAR), that is, sulfated polygalactose, can enhance both lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production and the rate of lethality in mice (M. Ogata, S. Yoshida, M. Kamochi, A. Shigematsu, and Y. Mizuguchi, Infect. Immun. 59:679-683, 1991). It has been reported that platelet-activating factor (PAF) antagonists reduce the rate of mortality from endotoxin shock. However, there are few reports regarding the effect of PAF antagonists on TNF production. The aim of the present study is to examine the effect of TCV-309, a new PAF antagonist, on LPS-induced TNF production and mortality in mice pretreated with CAR. ddY mice (6 to 7 weeks old) were injected intraperitoneally with CAR (5 mg per mouse) and were then divided into two groups: mice treated with a PAF antagonist (TCV-309; Takeda Pharmaceutical Co.) and control mice. The mice treated with PAF antagonist received indicated doses of TCV-309 subcutaneously (s.c.) at 30 min before LPS injection, while the control mice received 1 ml of saline s.c. at the same time. All mice were stimulated by intravenous injection of LPS (50 micrograms per mouse) at 24 h after pretreatment with CAR. At intervals after injection of LPS, serum samples were obtained for a TNF assay in which cytotoxicity to L929 cells was measured. TCV-309 both significantly suppressed LPS-induced TNF production and reduced mortality in a dose-dependent manner. When TCV-309 was administered at 30 min before injection of LPS, the effect of TCV-309 on the suppression of TNF activity was at its peak. Treatment with TCV-309 (990 micrograms per mouse) s.c. significantly improved the survival rate after challenge with LPS compared with the survival rate of control mice. Although the 50% lethal dose of LPS was 15 micrograms per mouse for control mice, it increased to 102 micrograms per mouse for mice that were treated s.c. with TCV-309 (990 micrograms per mouse). Even in vitro, TCV-309 also inhibited LPS-induced TNF production in thioglycolate-elicited macrophages. It was concluded that PAF plays an important role in endotoxin-induced TNF production and mortality.

Animals↗