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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Preoperative immunosuppression: its relationship with high morbidity and mortality in patients receiving thoracic esophagectomy.

The operative procedure for thoracic esophageal cancer, including thoracotomy, laparotomy, and three-field lymph node dissection, is a particularly stressful surgery that is characterized by high morbidity and mortality. The aim of this study was to evaluate the immunologic and nutritional states of patients to determine possible predictive factors of morbidity and mortality in patients receiving thoracic esophagectomy. Patients receiving thoracic esophagectomy were retrospectively divided into two groups. One group had postoperative infectious complications (group C+, n = 27), and the other had no complications (group C-, n = 76). They were treated with total parenteral nutrition or enteral nutrition providing 35-40 kcal. kg(-1). d(-1) of energy and 1.3-1.5 kcal. kg(-1). d(-1) of amino acids throughout the study period. The phytohemagglutinin (PHA)- and concanavalin A (Con A)-induced proliferation of peripheral blood mononuclear cells (PBMC) from the patients were measured before and at days 7 and 21 after the operation. Serum albumin, prealbumin, transferrin, the retinol binding protein, and the C-reactive protein were also evaluated. Three patients out of 27 in group C+ died because of severe infectious complications, whereas none of patients was fatal in group C-. PHA- and Con A-induced proliferation of PBMC was significantly low before the operation and remained suppressed on the 21st postoperative day in group C+. No significant difference was observed in nutritional status during the perioperative days between the two groups. Our results indicate that esophageal cancer patients with preoperative suppression of the cell-mediated immunity can be identified as a higher risk population in the postoperative period. When adequate nutrition is received, however, the correlation between nutritional status and mortality disappears.

Blood Proteins↗
PubMed2001

Congestion of superior mesenteric veins and small bowel mucosal injury after endoscopic treatment of esophageal varices in patients with portal hypertension.

We investigated treatment-induced changes in venous return from the small bowel and small bowel intestinal mucosal injury induced by the treatment of esophageal varices in patients with portal hypertension. A total of 14 patients (age 59.8+/-9.5 years, five women and 9 men) who received prophylactic treatment of esophageal varices between December 1998 and March 1999 were investigated. Diamine oxidase (DAO) activity was measured before and after treatment. Changes in blood flow of the portal and superior mesenteric veins were investigated by Doppler ultrasonography in six patients. A significant decrease in DAO activity was observed three days after treatment (11.5+/-1.6 units/liter prior to treatment versus 8.6+/-1.6 units/liter three days after treatment; P < 0.001). Decreases in superior mesenteric and portal venous flow velocity were observed in four and three patients, respectively. In two patients with an increase in the cross-sectional area of the superior mesenteric vein with delayed venous return, a marked decrease in DAO activity was observed three days after treatment. In patients with portal hypertension, rapid reduction of pooling of portal flow caused by the treatment of esophageal varices can induce transient congestion of the mesenteric venous system which can produce some small bowel mucosal injury.

Amine Oxidase (Copper-Containing)↗
PubMed2001

Differential effect of phosphodiesterase inhibitors on IL-13 release from peripheral blood mononuclear cells.

Increased cyclic AMP (cAMP)-phosphodiesterase (PDE) activity in peripheral blood leucocytes is associated with the immunological inflammation that characterizes allergic diseases, such as atopic dermatitis and allergic rhinitis. Recently, it has been found that IL-13 has similar biological functions to IL-4. The aim of this study was to investigate the possible involvement of cAMP-PDE activity on IL-13 release from peripheral blood mononuclears cells (PBMC) from atopic asthma patients. Phytohaemagglutinin (PHA)-induced IL-13 release from PBMC was concentration-dependently inhibited by rolipram, a type 4 PDE inhibitor, as well as by dibutyryl cAMP, a membrane-permeant cAMP analogue. However, theophylline, a non-specific PDE inhibitor, and cilostazol, a type 3 PDE inhibitor, failed to inhibit IL-13 release. The inhibitory effect of rolipram was enhanced by the addition of forskolin (10(-4) m), an adenylyl cyclase stimulator. PHA itself did not alter the intracellular cAMP level. Rolipram concentration-dependently increased cAMP level in PHA-stimulated PBMC, and this increase was synergistically facilitated by the addition of forskolin (10(-4) m). These results suggest that type 4 PDE inhibitors, alone or synergistically in combination with forskolin, inhibit PHA-induced IL-13 release from PBMC of atopic asthma patients by elevating intracellular cAMP concentrations. These inhibitors have the potential to exert an anti-inflammatory effect by inhibiting IL-13 production in allergic diseases such as atopic asthma.

Adult↗
PubMed2001

New pathway of amine oxidation respiratory chain of Paracoccus denitrificans IFO 12442.

The physiological electron acceptor of quinohemoprotein amine dehydrogenase (QH-AmDH) from Paracoccus denitrificans IFO 12442 was identified by biochemical and electrochemical methods. Of three types of heme c-containing proteins purified together with QH-AmDH from the periplasm of n-butylamine-grown cells, only constitutive cytochrome c-550 was reduced by the addition of QH-AmDH and n-butylamine. Reconstitution of the respiratory chain revealed that cytochrome c-550 mediates the electron transfer from QH-AmDH to the terminal oxidase. This is a new pathway of the amine oxidation respiratory chain of P. denitrificans.

Amines↗
PubMed2001

Osteochondritis dissecans of the lateral femoral condyle following total resection of the discoid lateral meniscus.

PURPOSE: The purpose of this study was to describe the clinical presentation of 6 athletically active children with symptomatic osteochondritis dissecans (OCD) of the lateral femoral condyle following total resection for a torn discoid lateral meniscus and to discuss its cause. TYPE OF STUDY: Case series. METHODS: Six patients in whom OCD affecting the lateral femoral condyle developed after total resection of the discoid lateral meniscus participated in a detailed clinical, radiologic, and arthroscopic review. The average age at the time of meniscectomy was 9 years (range, 6 to 12 years). At a mean of 50 months (range, 36 to 65 months) after surgery they developed recurrent pain in the treated knee; all had radiologic abnormalities at the lateral femoral condyle consistent with OCD. Before the recurrence of pain, all patients had been continuously engaged in sports activity. Radiologic and arthroscopic findings of the OCD lesions were assessed. Clinical outcomes of surgical treatment for OCD were also documented. RESULTS: The radiographic evaluation showed all lesions to be in the central portion of the lateral femoral condyle on the anteroposterior views and posteriorly next to a line extending distally from the posterior femoral cortex on the lateral views. Arthroscopic evaluation revealed softening in 2 knees, a separated fragment in 2 knees, and a completely loose fragment in 2 knees. All lesions were treated surgically, including 2 drillings of the lesion, 2 fixations of separated fragment, and 2 excisions of loose bodies with drilling. At an average follow-up period of 51 months (range, 22 to 77 months), all patients but 1 were asymptomatic. CONCLUSIONS: Repeated impaction in sports activities on the immature osteochondral structures under altered mechanical force transmission after total resection of the discoid meniscus might be a predisposing factor in the development of OCD in the lateral femoral condyle.

Adolescent↗
PubMed2001

The implication of repeated versus continuous strain on nerve function in a rat forelimb model.

We studied the effect of repeated and continuous nerve strain using a rat forelimb model to investigate whether an innocuous level of strain applied continuously affects nerve function when applied repeatedly. We used the rat medial cord of the brachial plexus and assessed the effects of strain by studying nerve histology (blood-nerve barrier), function (grasping strength), and electrophysiology. Continuous stretching was applied to the rat forelimb for 1 hour at 2 N. After this strain neither histologic analysis, grasping strength, nor electrophysiologic analysis revealed any effect. We then applied repeated strain at both 60 and 120 times per hour; after the latter strain abnormalities in histology, grasping strength, and nerve conduction were identified. There results suggest that a small nerve strain applied repeatedly results in nerve dysfunction. Our data may help explain the cause of nonspecific neural symptoms in the upper extremities of patients with no objective findings.

Animals↗
PubMed2001

Effects of a hydroxyl radical scavenger, EPC-K1, and neutrophil depletion on reperfusion injury in rat skeletal muscle.

Oxygen free radicals (OFR) and neutrophils are potent sources of reperfusion injury. We compared the effect of EPC-K1, a new OFR scavenger, and neutrophil depletion on the reperfusion injury in skeletal muscle, using an ischemic revascularized hindlimb model in rats. Warm ischemia, produced by vascular pedicle clamping, was sustained for 4 h. After 24 h of reperfusion, muscle function and damage were evaluated in 4 groups: a sham operation group, a control study group, a group treated by EPC-K1 (EPC group), and a group that received nitrogen mustard to induce neutropenia (NM group). Both the EPC and NM groups had limited muscle damage compared to the control group. The EPC group preserved muscle function significantly better than the control group and the mean isometric tetanic tension in the EPC group appeared to be higher than that in the NM group. Furthermore, levels of lipid peroxides in muscle and serum, and muscle edema in the EPC group, were significantly lower than in the NM group. Histological examinations supported these results. These findings suggest that limiting OFR generation by EPC-K1 in the early phase of reoxygenation is more potent than depletion of neutrophils in reducing reperfusion injury.

Animals↗
PubMed2001

Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in sputum from patients with bronchial asthma.

To examine a possibility that matrix metalloproteinases (MMPs) participate in the pathogenesis of asthma and/or the development of asthma attack, we measured the concentrations of MMP-2, MMP-9, and their respective tissue inhibitors of metalloproteinases (TIMP)-2 and TIMP-1, in induced sputa collected from 28 patients with moderate to severe bronchial asthma. Specimens were collected during both the attack and the remission from 15 age- and sex-matched healthy control subjects. The concentration of MMP-9 was significantly (p < 0.05) higher in the patients, even during the remission, as compared to that in healthy controls. The concentrations of MMP-9 (p < 0.05) and its specific inhibitor TIMP-1 (p < 0.01), and MMP-2 (p < 0.01) in these patients during the attack were significantly higher than those in healthy controls. In these patients, the MMP-9 concentration was significantly higher (p < 0.05) during the attack than during the remission. These results suggest that MMPs and TIMPs may be involved in the pathogenesis of bronchial asthma, and that the increased MMP-9 might be involved in the development of attack in patients with chronic asthma.

Adolescent↗
PubMed2001

Effects of theophylline withdrawal in well-controlled asthmatics treated with inhaled corticosteroid.

We examined effects of theophylline withdrawal in 17 adult asthmatics whose symptoms were well controlled under a treatment of a combination of theophylline and inhaled beclomethasone dipropionate (iBDP). We measured daily symptoms, daily peak flow values, spirometry, peripheral blood eosinophil count (EOS), and serum eosinophil cationic protein (sECP) at intervals of 1-3 weeks for 3 months after theophylline withdrawal. Twelve patients experienced exacerbation of asthma (exacerbation group), whereas the remaining 5 patients exhibited no symptoms (stationary group). In the exacerbation group, forced expiratory volume in 1 sec (FEV1) and percent vital capacity (% VC) gradually decreased until exacerbation of asthma, and the extent of these decreases within the first week after the withdrawal was greater compared with that at later than the third week. V25/HT decreased in both the exacerbation and stationary groups. In particular, the extent of the velocity of expiratory flow at 25% of the vital capacity/height (V25/HT) decrease in the exacerbation group was much greater than that of FEV1 or % VC in this group. Neither EOS nor sECP changed significantly during the clinical course in any patient. The rapid decrease in FEV1 and % VC after the withdrawal suggests that under treatment with iBDP, theophylline causes direct bronchodilating effects on smooth muscle, rather than anti-inflammatory effects. These results also suggest the importance of theophylline on peripheral as well as central airways.

Adult↗
PubMed2001

Cardiac functional and structural alterations induced by endotoxin in rats: importance of platelet-activating factor.

OBJECTIVE: In this study, we evaluated the time course of the alterations in left ventricular (LV) dimensions, LV wall thickness, and LV systolic function in rats with endotoxemia by using echocardiography as well as myocardial histopathologic assessments. Our second goal was to examine whether pretreatment with a platelet-activating factor (PAF) antagonist would ameliorate the lipopolysaccharide (LPS)-induced cardiovascular collapse during the early phase. DESIGN: A prospective, controlled, in vivo animal laboratory study. SETTING: Research laboratory at a university. SUBJECTS: Male, Wistar rats (8-9 wks old; n = 83). INTERVENTIONS: In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein also was catheterized for the administration of drugs. LPS (2 mg/kg) derived from Klebsiella pneumoniae or physiologic saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with an 8- to 13-MHz transducer. MEASUREMENTS AND MAIN RESULTS: LPS administration immediately induced progressive hypotension. The maximal hypotensive response was observed at 10 mins after LPS infusion with mean arterial pressure decreasing from 119 +/- 2 to 56 +/- 3 mm Hg (p < .001). LV end-diastolic internal dimensions decreased from 6.4 +/- 0.1 to 3.1 +/- 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced compared with control rats. LV end-systolic dimensions also decreased dramatically from 3.5 +/- 0.2 to 0.5 +/- 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45 +/- 1% to 84 +/- 2% (p < .001) at 30 mins after LPS and remained elevated compared with control rats. LV wall thickness increased strikingly from 15 mins until 2 hrs after LPS infusion. Pathologic studies demonstrated marked congestion of capillaries and mild edema in the LV myocardium. The hematocrit increased after the administration of LPS. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma concentrations of epinephrine and norepinephrine. There was no elevation of concentrations of nitrite and nitrate. Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated LV functional and structural changes. TCV-309 administration reduced the LPS-induced adrenergic activation and hemoconcentration. CONCLUSIONS: The hypotension that occurred during the initial phase of LPS-induced shock was accompanied by LV functional and structural alterations. The marked increase in LV wall thickness can be ascribed to the congestion of capillaries and edema in the LV myocardium. Pretreatment with a PAF antagonist reduced LPS-induced alterations. PAF may play a pivotal role during the initial phase of LPS-induced cardiovascular responses.

Animals↗
PubMed2001

[Murine typhus infected in Oku-etsu area, Fukui Prefecture].

A 15-year-old girl, high school student, became febrile (38-39 degrees C) with chills, sore throat and cough on April 20, 1994. Until the onset, she was healthy and she had been camping with her classmates in a wooded mountainous area in Oku-etsu, Fukui Prefecture. She consulted a local clinic on April 21 and bacampicillin was initially administered and then changed to cefaclor on April 23. However, high body temperature continued and a maclopapular rash appeared on her face on April 24 and gradually spread to her anterior chest and back. Blood examination showed a WBC count of 2,200/microliter, and she was admitted to our hospital on April 25. On admission, peripheral blood data showed leukocytopenia (WBC 2,300/microliter) with 5% atypical lymphocytes. Titers of anti-Rickettsia typhi serum antibodies (IgM, -G) were elevated (1:80, 1:640) and she was diagnosed as having murine typhus. On the second hospital day, 200 mg of minocycline (MINO) was administered per os and her body temperature fell to within the normal limits on the third hospital day. On the 7th hospital day, the skin rash disappeared and she was discharged. Altogether, 320 high school students went camping with this patient. Among them, approximately 30 students had similar symptoms and signs as this case and had been diagnosed suspected viral infection. Twelve students of the 30 were admitted to other hospitals. It was considered that this case was part of an outbreak of murine typhus in the Oku-etsu area, Fukui Prefecture, but no further investigation was performed. Murine typhus is usually a benign disease that is controllable by the administration of MINO. In rare cases, infection can worsen to multiorganic failure, severe complications have been reported in 1-4% of cases, and death has been reported in less than 3%. Recently, it has also been reported that MINO not only has an antibiotic effect, but also play acts as a cytokine modulator in patients with rickettsial infection. Thus, in febrile patients in whom uncommon Rickettsia infection is suspected, serological test for murine typhus should be examined and the immediate administration of MINO is important.

Adolescent↗
PubMed2001

Effect of endotoxin on P-glycoprotein-mediated biliary and renal excretion of rhodamine-123 in rats.

The effects of Klebsiella pneumoniae endotoxin on the biliary excretion and renal handling of rhodamine-123 were investigated in rats at different times after intraperitoneal injection (1 mg/kg of body weight). The typical substrates for P glycoprotein, i.e., cyclosporine, colchicine, and erythromycin, inhibited the biliary clearance of rhodamine-123, whereas a substrate for organic cation transporter, cimetidine, did not inhibit clearance, suggesting that rhodamine-123 is transported mainly by P glycoprotein. The biliary, renal, and tubular secretory clearances of rhodamine-123 and the glomerular filtration rate significantly decreased 6 h after injection of endotoxin but returned to control levels by 24 h. These results suggest that endotoxin-induced decreases in P-glycoprotein-mediated biliary excretion and renal handling of rhodamine-123 were probably due to impairment of P-glycoprotein-mediated transport ability. Pretreatment with pentoxifylline (50 mg/kg) significantly inhibited endotoxin-induced increases in tumor necrosis factor alpha (TNF-alpha) levels in plasma, which ameliorated the endotoxin-induced reduction of the biliary excretion of rhodamine-123. It is likely that endotoxin-induced impairment of the transport of rhodamine-123 is caused, in part, by overproduction of TNF-alpha. The effect of endotoxin on the expression of P-glycoprotein mRNA in liver and kidneys of rats was investigated by using a reverse transcriptase PCR. The expression of Mdr1a mRNA in both liver and kidney decreased 6 h after endotoxin injection and returned to control levels after 24 h, whereas the expression of Mdr1b mRNA in liver increased at both times and that in kidney decreased at 24 h. These findings suggest that K. pneumoniae endotoxin dramatically decreases P-glycoprotein-mediated biliary and renal excretion of rhodamine-123 probably by decreasing the expression of Mdr1a, which is likely due to increased plasma TNF-alpha levels.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Post-ischemic administration of DY-9760e, a novel calmodulin antagonist, reduced infarct volume in the permanent focal ischemia model of spontaneously hypertensive rat.

We assessed the effect of a novel calmodulin antagonist, DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate) in a spontaneously hypertensive rat (SHR) permanent focal cerebral ischemia. In experiment I, the left middle cerebral artery was permanently occluded in 62 SHRs. DY-9760e (0.5 mg kg(-1) h(-1)) or vehicle alone were administered continuously i.v. for 6 h, beginning 0, 30, or 60 min after the arterial occlusion. The infarct volume was measured 24 h of ischemia. In experiment II, the effect of DY-9760e on CBF was assessed in 10 SHRs. Administration without a delay resulted in a mean infarct volume of 166.7 +/- 21.0 mm3 (vehicle; n = 10) and 125.1 +/- 31.8 mm3 (DY-9760e; n = 9). Administration with a 30 min delay resulted in a mean infarct volume of 173.2 +/- 32.4 mm3 (vehicle; n = 12) and 143.3 +/- 35.3 mm3 (DY-9760e; n = 11). Dy-9760e significantly reduced the infarct under these conditions (p < 0.05). The administration with a 60 min delay failed to reduce the infarct. DY-9760e had no effect on the CBF. Continuous i.v. administration of DY-9760e reduced infarct volume in a SHR permanent focal ischemia without affecting ischemic CBF.

Animals↗
PubMed2001

Induction of histamine release from rat peritoneal mast cells by histatins.

Human salivary histatins (Hsts), which belong to a salivary polypeptide family, have potent antifungal activity against Candida albicans and Cryptococcus neoformans, and are expected to be useful as therapeutic reagents against Candida species. However, little is known about the effect of Hsts on host immune systems. Thus we conducted a series of in vitro experiments with rat mast cells to determine whether histatin 5 (Hst 5) or histatin 8 (Hst 8) has a histamine-releasing effect on mast cells. Both Hst 5 and Hst 8 induced histamine release from rat peritoneal mast cells in a dose-dependent manner (10(-9) to 10(-5) M). Hst 5 had a stronger releasing effect than Hst 8. The histamine release induced by Hst 5 (10(-6) M) was increased by the presence of 0.5 mM Ca2+, but decreased by 2mM Ca2+. Alternatively, the histamine release induced by Hst 8 (10(-6) M) was inhibited by the presence of Ca2+ (0.5 to 2 mM). These results suggest that Hsts have limited usefulness as therapeutic agents due to induction of histamine release from mast cells.

Animals↗
PubMed2001

Characterization of microsphere embolism-induced impairment of learning and memory function and the cholinergic system.

The impairments of learning and memory function and of the cholinergic system were examined in rats with microsphere embolism. Microsphere embolism was induced by injection of 900 microspheres with a diameter of 48 microm into the right internal carotid artery. The retention latency of a passive avoidance test was shortened and the escape latency of a water maze test was prolonged, when the animals were tested on the 5th to 10th day after the embolism, suggesting learning and memory dysfunction. Cholinergic parameters of the striatum and hippocampus, such as acetylcholine (ACh) content (67 and 60% decrease, respectively), choline acetyltransferase (ChAT) activity (45 and 56% decrease, respectively), and Bmax of muscarinic acetylcholine M1-receptor (43 and 37% decrease, respectively), were reduced on the 11th day after the embolism, suggesting attenuation of ACh synthesis and a decrease in the number of muscarinic acetylcholine M1-receptors mainly in the striatum and hippocampus. Areas not stained with triphenyltetrazolium chloride, an indication of infarction, were detected mainly in the striatum and hippocampus and partly in the frontal cortex on the 11th day after the embolism. The results suggest that an animal with microsphere embolism may be a good ischemic model with relatively sustained impairments of learning and memory function and of the striatal and hippocampal cholinergic system.

Animals↗
PubMed2001

Proteasomes are involved in the constitutive degradation of growth hormone receptors.

In the mouse Ba/F3-hGHR cell line, which stably expresses human growth hormone receptors (hGHRs), the hGHRs were rapidly degraded in the absence of the ligand. Human growth hormone-binding protein (hGH-BP), a soluble form of hGHR, was released from Ba/F3-hGHR cells, but the hGH-BP release was less than 1% of total hGHRs in the cells. Therefore, the hGH-BP release does not markedly contribute to hGHR degradation in Ba/F3-hGHR cells. The constitutive degradation of hGHRs was inhibited by the proteasome inhibitors MG-132 and clasto-lactacystin beta-lactone, or the vacuolar H+-ATPase inhibitor, bafilomycin A1. hGH-enhanced degradation of hGHRs was also inhibited by MG-132. Moreover, MG-132 inhibited the internalization of hGHRs as assessed by 125I-hGH binding to the cell surfaces. Ubiquitinated hGHRs were detected in the cell lysate and increased by hGH-treatment. Furthermore, MG-132 accumulated the ubiquitinated hGHRs induced by hGH. However, the ratio of ubiquitinated hGHRs to unubiquitinated hGHRs was very small, even with treatment involving both hGH and MG-132. In the hGH-untreated cells, the ubiquitinated hGHRs were weakly detected. However, the ubiquitination of hGHR was not enhanced by MG-132 as a result of immunoblotting. Thus, the ubiquitination of hGHR is unlikely to be involved, at least in the constitutive degradation. Taken together, both the proteasome pathway and endosome/lysosome pathway are involved in the constitutive degradation of hGHRs. Our results also suggest that ubiquitination of the hGHR itself is unlikely to be the trigger of the proteasome-dependent degradation.

Animals↗