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Biomedical subjects

K Iizuka

Publications and source records attributed to K Iizuka.

At least 91 records · Page 5Linked to original sources
PubMed1994

[The effect of induction chemotherapy with CBDCA, 5-FU and UFT in head and neck cancer].

Induction chemotherapy of low-dose CBDCA, 120-hour continuous infusion 5-FU and UFT was applied to 22 patients with untreated head and neck cancer. CBDCA 75 mg/m2 was given on day 1 and, subsequently, 5-FU 1,500 mg/m2/day for 120-hour continuous infusion was started. UFT was administered every day orally at 400-600 mg/day as biochemical modulation. If tumors were reduced and side effects were mild, these schedules were repeated after two weeks. Three patients (14%) achieved a CR and 11 (50%) a PR, for an overall response rate of 64%. Anorexia, nausea, vomiting and stomatitis were the predominant toxicities. They were mild and well tolerable, although severe diarrhea was observed in one case. Good general conditions of patients were kept because of low grade of toxicities. They were important factors for the tolerance of subsequent radiotherapy and surgery. Based on these results, we conclude that the combination of low-dose CBDCA, 5-FU and UFT as biochemical modulation is effective in head and neck cancer.

Administration, Oral↗
PubMed1993

Increased calcium release from sarcoplasmic reticulum stimulated by inositol trisphosphate in spontaneously hypertensive rat heart cells.

It is known that inositol (1, 4, 5)-trisphosphate (IP3) stimulates Ca2+ release from sarcoplasmic reticulum (SR) in several tissues, but in cardiac myocytes this phenomenon has not been confirmed. The purpose of the present study was to confirm the effect of (1, 4, 5)-IP3 on Ca2+ release from SR in cardiac myocytes. The effect of IP3 on Ca2+ release from SR in hypertrophic cardiac cells was also determined. We examined the effects of IP3 on Ca2+ release from cardiac myocyte SR by the digital-image method in a single cell. We also determined the effect of IP3 on calcium release from isolated SR. SR was prepared from spontaneous hypertensive rat hearts and Wistar kyoto rat hearts. The SR was prelabeled with 45Ca2+, and then incubated with the indicated concentrations of IP3 for 1 min at 37 degrees C. In cardiac myocytes treated with saponin, Ca2+ release stimulated by 10 microM (1, 4, 5)-IP3 was detected by fura-2. In 45Ca2+ prelabeled SR, the maximal Ca2+ release was achieved at 10 microM IP3 incubated for 1 min. The release of Ca2+ was higher in SR of SHR than in the SR of WKY. IP3 stimulates Ca2-release from cardiac SR, and this release is greater in SHR than in WKY. However, it is uncertain whether this phenomenon plays a role in cardiac hypertrophy.

Animals↗
PubMed1993

Effects of thiol protease inhibitors on fodrin degradation during hypoxia in cultured myocytes.

The effects of thiol protease inhibitors on fodrin (a cell membrane nonerythroid spectrum-like protein) degradation were studied during hypoxia in cultured myocytes. Cardiac myocytes, isolated from neonatal rat hearts, were incubated under hypoxic conditions for 6 h. Cell membrane proteins, including fodrin, prepared from hypoxic myocytes were examined with electroblots stained for fodrin by the peroxidase method. Cell death during hypoxia rose to 80% after 6 h. Intracellular protease activity was also elevated in hypoxia. This intracellular protease activity was markedly inhibited by the cysteine protease inhibitor E-64 and calpain inhibitor 1. Hypoxic cell death was also suppressed by E-64 and calpain inhibitor 1. A 125 kDa immunoreactive degradation product of fodrin was found in hypoxic conditions. Treatment with E-64 and calpain inhibitor 1 decreased both the appearance of this band and the degradation of fodrin. These observations indicate that intracellular thiol proteases, including calpains, are activated during hypoxia and that these are related to cell membrane protein degradation, especially of fodrin. The data also suggest that protease inhibitor E-64 treatment may be beneficial in protection against hypoxic myocyte injury.

Animals↗
PubMed1993

Urinary epidermal growth factor levels in patients with acute renal failure.

To investigate the importance of epidermal growth factor (EGF) in patients with renal dysfunction, urinary human EGF (hEGF) levels were determined by radioimmunoassay in 16 patients with acute renal failure (ARF) and in 12 healthy controls. Seven patients with chronic renal failure also were studied. Urinary hEGF levels, corrected for urine creatinine concentrations, were significantly decreased in patients with ARF in the acute phase compared with normal control subjects (0.98 +/- 0.20 v 13.74 +/- 1.18 ng/mg creatinine, P < 0.001), and subsequently increased during the recovery phase (6.10 +/- 0.73 ng/mg creatinine, P < 0.001 v acute phase). A significant positive correlation existed between urinary hEGF levels and creatinine clearance in patients with ARF (r = 0.66, P < 0.001). Serum hEGF levels also were significantly lower in patients with ARF compared with normal control subjects (0.10 +/- 0.01 v 0.30 +/- 0.03 ng/mL, P < 0.001). No significant correlation was found between hEGF concentrations in serum and urine. In conclusion, measurement of urinary hEGF may be useful in the diagnosis of ARF and for following the recovery of the kidney after severe tubular injury.

Acute Kidney Injury↗
PubMed1993

Phosphatidylinositol metabolism in hypertrophic rat heart.

The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during cellular response to norepinephrine in pressure-overloaded hypertrophic rat heart. After stimulation with norepinephrine, the accumulations of IP3 and diacylglyceride significantly increased in isolated myocytes from stroke-prone spontaneously hypertensive rat (SHRSP) heart, indicating phosphatidylinositol-specific phospholipase C activity increased in SHRSP heart cells. Protein kinase C activity was also enhanced in SHRSP, with a marked increase in particulate activity. We determined the intracellular calcium concentration and found it to be higher in SHRSP than in Wistar-Kyoto (WKY) rats at 30-40 weeks of age. Ca2+ influx was also elevated in SHRSP stimulated by norepinephrine. In SHRSP heart, cytosolic Ca2+ concentration may rise quickly in response to some stimuli, such as alpha 1-adrenergic stimulation, which is shown to be one of the pathways that increases cytosolic Ca2+ levels in hypertrophied rat heart. These data suggest that a part of the phosphatidylinositol-turnover pathway, such as the phosphatidylinositol 4,5-bisphosphate-IP3-Ca2+ pathway or the diacylglyceride-protein kinase C pathway, may play an important role in the development of hypertrophy in SHRSP heart.

Animals↗
PubMed1993

Pharmacological profile of KSG-504, a new cholecystokinin-A-receptor antagonist.

Pharmacological effects of KSG-504, a newly synthetized compound, on the response induced by exogenous CCK-8 were investigated. KSG-504 inhibited 125I-CCK-8 binding to both rat pancreas and cerebral cortex with IC50 values of 2.0 x 10(-7) M and 8.0 x 10(-5) M, respectively. The selectivity ratio of KSG-504 for pancreatic CCK receptor (CCK-A) was estimated as 400. In the isolated pancreatic acini of rats, KSG-504 caused a parallel rightward shift of the concentration-response curve for CCK-8-stimulated amylase release with no change in its maximal response, indicating a competitive antagonism of the drug for the CCK-A receptor (Schild plot analysis; slope = 0.927, pA2 = 6.9). In addition, KSG-504 produced a significant inhibition of CCK-8-induced pancreatic amylase secretion when administered intravenously or intraduodenally to rats (ED50: 52 micrograms/kg/min by the i.v. route and 12.1 mg/kg by the i.d. route). KSG-504 had equipotent inhibitory effects on both CCK-8-stimulated pancreatic secretion and gallbladder contraction in dogs with ED50 values of 0.98 and 0.84 mg/kg, respectively. KSG-504 also inhibited the CCK-8-induced contraction of isolated guinea pig ileum in a concentration-dependent manner (IC50 = 3.0 x 10(-6) M). These results demonstrate that KSG-504 is a competitive and selective CCK-A-receptor antagonist that is effective in vivo after oral administration.

Amylases↗
PubMed1993

[Immunohistochemical localization of epidermal growth factor in proximal tubules of rats with acute renal failure].

Increasing evidence supports the hypothesis that epidermal growth factor (EGF) may have a role in the repair of tubular injury on acute renal failure (ARF). On the other hand, platelet-depletion reduces the renal damage in experimental ARF rats. We investigated the expression of EGF in the renal tissues of mercuric-chloride (HgCl2, 2mg/kg)-induced ARF rats with (group-1) or without (group-2) platelet depletion for clarification of the role of EGF in the recovery of the renal tubules after ARF. Platelet-depletion was accomplished by the injection of anti-rat platelet serum (APS) 24 hours prior to the induction of ARF. The tubular necrosis and deterioration of renal function were significantly suppressed in group-1 compared with group-2 24 hours after HgCl2 injection (S-Cr 0.60 +/- 0.17 mg/dl, Ccr 0.58 +/- 0.11 ml/min in group-1 and 1.45 +/- 0.10 mg/dl, 0.20 +/- 0.02 ml/min in group-2, p < 0.05) but were in the same range between both groups 12 hours after (S-Cr 0.75 +/- 0.03 mg/dl, Ccr 0.49 +/- 0.02 ml/min in group-1 and 0.60 +/- 0.05 mg/dl, 0.67 +/- 0.08 ml/min in group-2). By immunohistochemistry, EGF was localized in the ascending limbs of Henle and distal convoluted tubules in normal rats. However, in both ARF rats, EGF was stained on the proximal tubules, including the necrotic area as well as the ascending limbs of Henle and distal convoluted tubules, both 12 and 24 hours after ARF induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Evaluation of airway smooth muscle contractions in vitro by high-frequency ultrasonic imaging.

To visualize ASM contraction in vitro, we measured changes in cross-sectional area and inner circumference of isolated porcine and human bronchi in response to acetylcholine or carbamylcholine chloride (Carbachol) using high-frequency ultrasound. A mechanical ultrasonic catheter (20 MHz; diameter, 1.7 mm; echo element, 1 mm2) demonstrated three histologic layers (mucosa, cartilage and adventitia) and allowed measurement of dose-dependent contraction of porcine bronchi over time. Acetylcholine (10(-4)M) significantly decreased the cross-sectional area by 17 +/- 2.85 percent but did not change the circumference. The mean initial value for area was 0.6 +/- 0.08 cm2 and for circumference was 3.0 +/- 0.24 cm (n = 5). The EC50 of acetylcholine was 1.5 x 10(-8) M. Carbachol (10(-4)M)-induced contractions of human bronchi were also observed under the same conditions. In conclusion, high-frequency ultrasonic imaging can be used to study the morphology of ASM contractions in vitro, providing valuable information on the natural dynamics of ASM.

Acetylcholine↗
PubMed1992

The role of calcium activated neutral protease on myocardial cell injury in hypoxia.

The aim of this study was to investigate the correlation between hypoxic myocardial cell injury and intracellular protease activity. Cardiac myocytes were isolated from neonatal rat hearts and cultured in Eagle's modified minimum essential medium. Myocytes were incubated in hypoxic conditions for 6 hours. The cell death rate during hypoxia rose to 80% after 6 hours. Extracellular protease activity was elevated to 4 units during hypoxia, much higher than the 0.7 units in aerobic states at 6 hours. This extracellular protease activity in hypoxic conditions was markedly inhibited by leupeptin and EDTA, and weakly inhibited by the cysteine protease inhibitor, NCO-700, but phenylmethyl sulfonyl fluoride did not inhibit the protease activity. To identify the protease activated during hypoxia, calpain-specific inhibitors were added to the incubation mixture. Calpain inhibitor 1 and calpastatin, an endogenous selective calpain inhibitor, markedly inhibited extracellular protease activity during hypoxia. NCO-700 also inhibited intracellular protease activity. NCO-700 reduced hypoxic cell death to 30% after 6 hours of hypoxygenation. These observations indicate that calpain is activated during hypoxia and leads to irreversible cell membrane degradation after 6 hours of hypoxygenation.

Animals↗
PubMed1992

[Hemispheric differences in letter matching of hiragana and katakana].

The purpose of the present study was to examine the hemispheric differences in letter matching of hiragana and katakana. The stimuli with a pair of each one letter of hiragana and katakana were presented unilaterally to the right or left visual hemifield with a tachistoscope. The subjects were 40 male right handers. They were required to judge whether a pair of letters had the same name or different one. A significant right visual hemifield superiority was observed for both the accuracy of recognition and reaction time. The results suggest that the callosal relay model of Zaidel may be applied to the name matching task.

Brain↗
PubMed1992

[Deep neck infection following endotracheal intubation].

A 71-year-old woman was transferred to Kushiro City General Hospital because of fever, sore throat, diffuse neck swelling and dyspnea. She had received right mastectomy for breast cancer under general anesthesia 6 days before the admission. The lateral X-ray film of the neck revealed abscess in the retropharyngeal space and the retroesophageal space. CT scan revealed mediastinitis. Next day she received neck dissection for drainage of the abscess under general anesthesia. Although the posterior pharyngeal wall was swollen, endo-tracheal intubation was not difficult. Brown tinged and purplish pus was aspirated from the interspace of carotid sheath and trachea, the retropharyngeal space, and the superior mediastinal space. The infected site was irrigated with a lot of peroxide and saline and draining tubes were placed in each interspace. Tracheostomy was not done but the patient was admitted to the ICU with her trachea intubated. The day after operation, she was extubated. Three days after the operation chest X-ray revealed pyothorax and chest tube was inserted for drainage. Seven days after the operation she was transferred to the ENT ward. Thereafter her recovery course was uneventful. It seems that the deep neck infection was probably caused by the injury on endotracheal intubation at the first operation in this case. Although this patient was cured of mediastinitis following deep neck infection, which is still lethal, early diagnosis and surgical drainage of the abscess are necessary.

Abscess↗
PubMed1992

[Depth perception and amplitude of VEPs for variations of dot density in static random dot stereograms].

Relative changes in depth perception and amplitude of VEPs were compared when the dot density in static random dot stereograms was altered. The maximum amplitudes of negative potentials evoked by either stereogram or uncorrelogram were recorded from the occipital region of human scalp. The peak latency was in the range of 160 to 260 msec, averaging 197 msec in 18 subjects. The amplitude of negative potentials evoked by either stereogram or uncorrelogram was always larger than that evoked by correlogram. The amplitudes on either stereograms, uncorrelograms or correlograms did not significantly increase when the dot density was increased, and there was no significant difference in amplitude on either stereogram or uncorrelogram. Depth perception did not closely correlate with the dot density nor with the amplitude of negative potentials. These results suggest that the amplitude of negative potentials may represent activities of disparity-sensitive neurons elicited in a trigger feature manner, but it does not reflect activities of the higher order process of depth perception.

Adult↗
PubMed1992

[Changes of urinary human epidermal growth factor excretion in 16 patients with acute renal failure].

In order to evaluate the clinical significance of urinary human epidermal growth factor (hEGF) in patients with acute renal failure (ARF), urinary hEGF levels were determined by radioimmunoassay, and were corrected for creatinine (creat.) concentrations in 16 patients with ARF and 12 healthy controls. The urinary hEGF levels significantly decreased in patients with ARF in acute phase compared with normal control subjects (0.98 +/- 0.20 vs 13.74 +/- 1.18 ng/mg creat. p less than 0.01), and it subsequently increased during recovery phase (6.10 +/- 0.73 ng/mg creat. p less than 0.01 vs acute phase). A significant correlation between the urinary hEGF levels and creatinine clearance (r = 0.712, p less than 0.001) and an inverse correlation between urinary hEGF levels and fractional excretion of sodium (r = -0.406, p less than 0.05) was demonstrated. The remarkable decrease of urinary hEGF excretion preceded the increase of urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase levels. Our data suggests that urinary hEGF originates from renal tissues in humans and measurement of urinary hEGF is useful for diagnosing renal damage and recovery of renal tissues from severe tubular injury.

Acetylglucosaminidase↗
PubMed1991

Phospholipid metabolism and prostacyclin synthesis in hypoxic myocytes.

We observed that in hypoxic myocardial cells prostacyclin and arachidonic acid release increased and that during hypoxia phospholipid degradation also occurred. In order to clarify the mechanism of phospholipid degradation, we determined the activity of phospholipases A2 and C. We found that phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were markedly decreased and that lysophosphatidylcholine and lysophosphatidylethanolamine were increased. In contrast, there was only slight phosphatidylinositol degradation and no lysophosphatidylinositol elevation was observed. These results show that phospholipase A2 was activated in hypoxic myocytes and had substrate specificity towards PC and PE. To study phospholipase C activity, membrane phospholipids were labeled with [3H]choline, [3H]inositol or [3H]ethanolamine. The release of inositol was observed, but neither choline nor ethanolamine was released. In hypoxia, myocardial-cell phospholipase C has high substrate specificity towards phosphatidylinositol. The activation of phospholipases is closely related to the intracellular Ca2+ concentration; it is though that inositol polyphosphatides may regulate intracellular Ca2+. We determined how Ca2+ influx occurs in hypoxia. beta-Adrenergic blockade and Ca2+ antagonists markedly suppressed Ca2+ influx, phospholipase A2 activity, phospholipase C activity and cell death. However, the alpha 1-adrenergic blockade was less effective in suppressing these phenomena. These results suggest that in hypoxic myocardial cells Ca2+ influx mediated by beta-adrenergic stimulation activates phospholipases A2 and C, and that phospholipid degradation and prostacyclin release then occur.

Adenylyl Cyclases↗
PubMed1991

The leakage of fatty acid binding protein from cultured myocardial cells during hypoxia.

Fatty-acid binding protein (FABP) is thought to play an important role as a carrier protein of fatty acids in cells. It may leak from damaged cells, because its molecular weight is low (mol wt 14000) and it accounts for several percent of soluble protein. In this experiment we attempted to use FABP as a marker of cell injury under hypoxia in cultured myocytes. Newborn-rat myocytes were incubated under hypoxic treatment for 6 hours, and then the releases of FABP and CPK were measured. The cell-death ratio during hypoxygenation increased from 4 hours and rose to 80% at 6 hours, but it was only 8% under aerobic conditions. FABP in medium was detected at 1 hour, and rapidly increased and reached a plateau at 4 hours. On the other hand, CPK in medium was negligible during the 3 hours, then slightly increased. Ca antagonists and a beta 1-adrenergic blocking agent inhibited the release of FABP and prevented cell death. But the alpha 1-adrenergic blocking agent had little effect on preventing FABP leakage and cell death. These results show that FABP is of use as a marker of myocardial cell injury and revealed that the Ca antagonist and beta 1-adrenergic blocking agent are useful drugs for the protection of myocardial cell injury in hypoxia.

Adrenergic alpha-Antagonists↗
PubMed1991

Platelet aggregation induced by platelet-activating factor is suppressed by cystine protease inhibitor.

The effect of NCO-700, a cystine protease inhibitor, on platelet-activating factor-induced platelet aggregation was determined. A newly synthesized cystine protease inhibitor (calcium-activated neutral protease and cathepsin B inhibitor), NCO-700 (bis[ethyl (2R, 3R)-3-[(S)-methyl-1-[4-(2,3,4- trimethoxyphenylmethyl) piperazine-1-ylcarbonyl]butylcarbonyl]oxiran-2-carboxy late]sulfate), inhibited platelet-activating factor-induced platelet aggregation. The inhibition was dependent on the preincubation time with NCO-700 and on the concentration of the inhibitor. The release of serotonin was also inhibited almost completely by the 20-min preincubation with 10(-4) M NCO-700. Leupeptin also inhibited platelet-activating factor-induced platelet aggregation. But calcium-activated neutral protease inhibitor did not inhibit it. These observations suggest that NCO-700-sensitive protease(s) such as cystine protease may contribute to platelet aggregation induced by platelet-activating factor.

Animals↗
PubMed1991

Calpain is activated during hypoxic myocardial cell injury.

Cell death during hypoxia rose to 80% after 6 h. Calpain activity increased to 4 units during hypoxia, much higher than the 0.7 units seen in aerobic condition at 6 h. This activity was markedly inhibited by calpain-specific inhibitor I (n-acetyl-leucyle-leucyle-norleucinal). beta-Adrenergic blocking agents and calcium antagonists suppressed the calpain activity and decreased cell death during hypoxia. On the other hand, alpha-adrenergic blocking agents did not affect calpain activity and cell death under hypoxic conditions. These results prove that beta-adrenergic blocking agents and calcium antagonists prevent protein degradation during hypoxic cell injury.

Amino Acid Sequence↗