Search PubMed⌕ Search

Biomedical subjects

K Kodama

Publications and source records attributed to K Kodama.

At least 541 records · Page 30Linked to original sources

[Local chemo-hyperthermotherapy of recurrent rectal cancer].

Local radiofrequency hyperthermia combined with chemotherapy was performed on five patients with pelvic recurrence of rectal cancer. Relief of pain was obtained in all four patients with uncontrolled pelvic pain due to recurrent rectal cancer. In some patients, CEA levels of peripheral blood were decreased and tumor necrosis was proved histologically. These results suggest that this combined therapy may be useful for patients with pelvic recurrence of rectal cancer.

Adenocarcinoma↗

Antithrombin III binding to surface immobilized heparin and its relation to F Xa inhibition.

The mode of F Xa inhibition was investigated on a thromboresistant surface with end-point attached partially depolymerized heparin of an approximate molecular weight of 8000. Affinity chromatography revealed that one fourth of the heparin used in surface coating had high affinity for antithrombin III (AT). The heparin surface adsorbed AT from both human plasma and solutions of purified AT. By increasing the ionic strength in the AT solution the existence of high and low affinity sites could be shown. The uptake of AT was measured and the density of available high and low affinity sites was found to be in the range of 5 and 11 picomoles/cm2, respectively. Thus the estimated density of biologically active high and low affinity heparin respectively would be 40 and 90 ng/cm2. The heparin coating did not take up or exert F Xa inhibition by itself. With AT adsorbed on both high and low affinity heparin the surface had the capacity to inhibit several consecutive aliquots of F Xa exposed to the surface. When mainly high affinity sites were saturated with AT the inhibition capacity was considerably lower. It was demonstrated that the density of AT on both high and low affinity heparin determines the F Xa inhibition capacity whereas the amount of AT on high affinity sites limits the rate of the reaction. This implies that during the inhibition of F Xa there is a continuous surface-diffusion of AT from sites of a lower class to the high affinity sites where the F Xa/AT complex is formed and leaves the surface. The ability of the immobilized heparin to catalyze inhibition of F Xa is likely to be an important component for the thromboresistant properties of a heparin coating with non-compromised AT binding sequences.

Animals↗

Contribution of arterial redox potential measurement to the care of critically ill patients.

175 arterial and 122 urinary samples from 20 patients admitted in ICU for organ system failure (OSF) were analysed. Besides arterial blood gases and lactate, electrolyte concentrations, pH, rH2 and specific resistance (R) in blood and urine were measured. Redox potential (E) and base excess were calculated from these data. Patients were defined as having MOSF if their organ systems met failure criteria during their ICU stay. Data were classified with corresponding number of OSF developed in the patients when samples were obtained. Acid-base balance or base excess alone could not be used to predict the severity of illness as assessed by increasing number of organ system failures. Significant elevations in blood lactate concentrations were observed only in patients with four, five or six OSF. A lack of correlation between blood lactate and severity of OSF indicates that blood lactate is not valid as a guide to ultimate outcome of the patients. Arterial redox potentials progressively decreased with increasing number of OSF, therefore, it can be stated that the serial measurements of arterial redox potential are useful in assessing the patient's status or predicting their ultimate outcome.

Journal Article↗

Atrial natriuretic polypeptide (ANP) in the development of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP).

In order to investigate the pathophysiological role of atrial natriuretic polypeptide (ANP) in genetic hypertensive rats, the atrial content and plasma concentration of ANP were measured by a sensitive radioimmunoassay (RIA) for rat ANP in 5-, 10- and 20-week-old spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared to age-matched Wistar Kyoto rats (WKY). Atrial content of immunoreactive ANP (ir-ANP) tended to be higher in SHR and was already significantly higher in SHRSP than in WKY at 5 weeks of age. Atrial content in the hypertensive strains became significantly higher than in WKY when hypertension developed at 10 and 20 weeks. On the other hand, plasma ir-ANP in SHR was significantly lower than in WKY at 5 weeks, however, it became significantly higher in both SHR and SHRSP than in WKY at 10 and 20 weeks. These findings suggest that ANP release may increase to compensate for the elevation of blood pressure in SHR and SHRSP and that biosynthesis of ANP may be concomitantly stimulated, resulting in an increase in atrial ANP.

Aging↗

Nucleotide sequence comparison of the predicted first exonic region of goldfish ras gene between normal and neoplastic tissues.

The first exonic and its flanking regions of a ras-related gene in cultured erythrophoroma cells and normal liver of goldfish (Carassius auratus) were sequenced and their sequences compared. The two samples demonstrated identical sequences for the Alu I fragment of 245 nucleotides, of which 70 nucleotides might correspond to the 5'-upstream segment and 64 to the first intervening sequence, indicating that the predicted exonic region encodes from the 1st to the 37th amino acids from the N-terminal of mammalian ras protein. The length of the predicted first exon of goldfish was the same as that of mammals. There was a 5 nucleotide difference in this exonic region (length 111 nucleotides) from another previously determined ras-related sequence of normal goldfish. This difference was much smaller than that between any two of the three mammalian ras genes. Enhanced expression of ras gene was observed in erythrophoroma cells, although it was uncertain which ras gene was responsible for generation of the observed RNA.

Animals↗

Effect of aortocoronary bypass surgery on coronary circulation and myocardial metabolism during atrial pacing.

Eleven patients with coronary heart disease, in whom at least one of several bypass grafts to the left coronary artery was patent, were selected for the study. The hemodynamics, coronary sinus blood flow, myocardial oxygen consumption, and myocardial lactate metabolism were evaluated at rest and during atrial pacing stress test before and after surgery. There were no significant improvements in the cardiac index, pulmonary arterial end-diastolic pressure, and left ventricular ejection fraction after aortocoronary bypass surgery. However, significant improvement of coronary sinus blood flow, myocardial oxygen consumption, and myocardial lactate extraction and consumption were found during postoperative atrial pacing compared with the preoperative findings. These results suggest that successful bypass grafting may improve myocardial lactate metabolism in ischemic lesions and contribute to the postoperative relief of angina.

Cardiac Pacing, Artificial↗

A multicenter study of a new inotropic agent, piperanometozine (OPC-8212) in congestive heart failure: clinical improvement during short-term treatment.

Piperanometozine (OPC-8212) is a new, orally effective inotropic agent. To evaluate the efficacy of this agent on systemic hemodynamics and clinical symptoms in patients with congestive heart failure, a multicenter study was performed. Thirty four patients with New York Heart Association (NYHA) functional classes II to IV and initially treated with digitalis were enrolled from ten centers. After a washout period of one or two weeks (placebo period), digitalis was replaced by piperanometozine (30 or 60 mg/day) for four weeks, while other drugs were continued. Clinical symptoms, routine physical findings, electrocardiogram, chest roentgenogram, echocardiogram, exercise tolerance time, and routine laboratory data were obtained in 34 patients. Four patients were withdrawn from the study before completion. After the withdrawal of digitalis, heart rate was increased and ejection fraction was decreased. Exercise tolerance time was increased while other parameters were unchanged. At the end of the treatment period with piperanometozine, ejection fraction significantly (p less than 0.05) increased with a decrease in LV end-systolic volume (p less than 0.05), whereas heart rate and blood pressure remained unchanged. Systolic blood pressure/LV end-systolic volume (P/V index) tended to decrease after the withdrawal of digitalis and increase during piperanometozine therapy. Exercise tolerance time was further increased (p less than 0.01) and NYHA functional class was improved in 11 patients, whereas it worsened in only one patient. No major adverse effects were observed. These results indicate that a short-term therapy of oral piperanometozine restored the depressed cardiac performance of the heart and improved clinical symptoms in patients with congestive heart failure. Thus, this promising agent deserves further clinical study in long-term trials.

Aged↗

Expression of HLA-DR antigens on colonic epithelium in ulcerative colitis.

Although the expression of HLA-DR antigens on colonic epithelium in ulcerative colitis has been observed by several groups, the results of the expression in remission have been conflicting and there has been virtually no study concerning the expression in non-inflamed area in active ulcerative colitis. We studied systematically HLA-DR expression on colonic epithelium in 37 patients with ulcerative colitis chronologically, namely in remission as well as in the active stage and inflamed and non-inflamed areas simultaneously in the active stage. HLA-DR antigens were detected by indirect peroxidase staining using anti-HLA-DR monoclonal antibody. We confirmed the previous observation that epithelium from control colon does not express HLA-DR antigens, while epithelium from ulcerative colitis expresses the antigens with high frequency (83.3 percent). In addition, we demonstrated that HLA-DR expression on colonic epithelium in active ulcerative colitis disappeared in remission. Our new finding was that there is no HLA-DR expression on colonic epithelium in non-inflamed mucosa in active ulcerative colitis. Namely HLA-DR antigens were expressed only on inflamed epithelium of ulcerative colitis. These results lead to the conclusion that the expression of HLA-DR antigens on colonic epithelium in ulcerative colitis is closely related to the inflammation of mucosa.

Colitis, Ulcerative↗

Efficient cleavage by alpha-thrombin of a recombinant fused protein which contains insulin-like growth factor I.

The gene for insulin-like growth factor I (IGF-I) was constructed from chemically synthesized deoxyoligonucleotides and expressed in Escherichia coli, under the control of a trp promoter, as a set of fusion proteins which were connected with a portion of human growth hormone through the recognition sequence for a sequence-specific protease, either blood coagulation factor Xa or alpha-thrombin. Upon induction with 3-indoleacrylic acid, fusion proteins accumulated with a yield of 10-30% of the total protein. A fusion protein connected through a tetradecapeptide (Asp-Asp-Pro-Pro-Thr-Val-Glu-Leu-Gln-Gly-Leu-Val-Pro-Arg) was efficiently and correctly cleaved by alpha-thrombin, and the purified IGF-I possessed somatomedin-like activity, as determined by the enhancement of sulfation of glycosaminoglycans in cultured costal chondrocytes from rabbits.

Biological Assay↗

Establishment and characterization of a T-cell line specific for Rickettsia tsutsugamushi.

To study the immunological protective system against rickettsial infection, a T-cell line specific for Rickettsia tsutsugamushi antigen was established by long-term culture of splenocytes from mice immunized with live Gilliam strain R. tsutsugamushi and then propagated in the presence of homologous rickettsial antigen and syngeneic filler cells. The characteristics of the T-cell line and its capacity to induce antirickettsial protection in vivo were studied. Flow cytometric analysis demonstrated that the T-cell line showed the phenotype Thy-1.2+ L3T4+ Lyt-2-, suggestive of helper T cells. In a lymphocyte proliferation assay, this cell line showed a specific response to Gilliam antigen, partial cross-reactivity to Karp antigen, but no response to Kato antigen. The proliferative response of this T-cell line was filler cell dependent, and genetic restriction was observed between the T-cell line and filler cells. The T-cell line produced gamma interferon, one of the macrophage-activating factors, in cultures with specific antigen and was able to adoptively mediate antirickettsial protection in vivo. The data presented here suggest that antigen-specific helper T cells play an important role in protection against rickettsial infection.

Animals↗

Effects of antiserum against alpha-rat atrial natriuretic peptide in anesthetized rats.

Although synthetic atrial natriuretic peptide is known to increase urinary volume and sodium excretion and to reduce arterial blood pressure, the physiological role of endogenous atrial natriuretic peptide is still unclear. We investigated the effects of specific rabbit antiserum against alpha-rat atrial natriuretic peptide on hemodynamics, diuresis, and natriuresis in anesthetized rats. A significant rise in mean blood pressure lasted for about 60 minutes after intravenous administration of the antiserum, with the maximal increment being approximately 7%. Similarly, a significant increase in cardiac output was obtained 20 minutes after injection at an increment of approximately 11%. Heart rate, however, remained unchanged. On the other hand, significant reductions in urine output and urinary sodium and potassium excretion lasted for about 20 minutes after administration of the antiserum, with maximal decrements being 63%, 63%, and 60%, respectively. No significant effects on hemodynamics, diuresis, and natriuresis were observed following injection of normal rabbit serum. These results indicate that endogenous atrial natriuretic peptide has an important physiological role in the regulation of hemodynamics and water-electrolyte balance.

Anesthesia↗

Randomized double-blind trial of intracoronary urokinase for acute myocardial infarction: multicenter study.

The efficacy of intracoronary urokinase (UK) in an acute myocardial infarction has not been firmly established in a randomized fashion. Two hundred and ten patients were randomized to UK therapy (107 patients) and placebo (103 patients). Successful recanalization was achieved in 74% of the UK group vs 17% in the placebo group (p less than 0.01). The success rate was dose dependent up to 960,000 I.U. Clinical course was favorable and left ventricular enddiastolic pressure was reduced significantly in the UK group compared with the placebo group (p less than 0.05). Ejection fraction one month after the study was better in the reopened group than in the occluded group. Thus, early administration of UK can establish coronary reflow in a high proportion of patients and appears to favor the clinical course.

Aged↗

Mechanism of luminal enlargement in PTCA and restenosis: a histopathological study of necropsied coronary arteries collected from various centers in Japan.

Necropsy studies of coronary arteries were made in 14 patients who died after percutaneous transluminal coronary angioplasty (PTCA). Eight patients died shortly after PTCA, while the other six patients died some considerable time later. A total of 9,920 serial step sections of necropsied coronary arteries at the site of PTCA were prepared and examined histopathologically by light microscope to determine the mechanism of luminal enlargement in PTCA, as well as the occurrence of restenosis. Of the eight patients who died shortly after PTCA, two had disruption of the intima and the media in the arterial wall located opposite the site that had atheroma, in spite of the fact that the former wall is more normal than the latter. Dissection of the media was camed out in four patients and intimal desquamation performed in six. All the patients revealed fresh thrombus formation. Of the six patients who survived for a long time after PTCA was performed, two had disruption of the intima and the media located opposite the site with atheroma. In one, the media was dissected and in another, intimal desquamation was camed out. In one patient, release of atheroma into the lumen was suspected. Proliferation of intimal cells was revealed in three patients indicating that restenosis had occurred. No compression of the atheroma was observed in any of the 14 patients. The above findings led to the conclusion that the mechanisms of luminal enlargement in PTCA are: 1) intimal and medial disruption in the arterial wall located opposite the atheroma; 2) medial dissection; 3) intimal desquamation; 4) release of atheroma into the lumen; and 5) any combination of 1) -4).

Adult↗

Acute electrocardiographic changes associated with successful coronary thrombolysis in acute myocardial infarction.

In this study ECG changes were analyzed to assess the acute effects of antegrade blood flow on the ECG in patients with AMI. The study population consisted of 22 patients with MI in whom the totally occluded left anterior descending artery (LAD) or right coronary artery (RCA) was recanalized by intracoronary urokinase infusion (recanalized group) and 14 patients in whom the occluded coronary artery was not successfully recanalized (control group). No significant difference was found in the sum of ST segment elevation (V2-V4 leads for the LAD-occluded group, II, III and aVF leads for the RCA-occluded group) before urokinase infusion. In the recanalized group sigma ST abruptly increased in 5 min after recanalization in 13 of 16 LAD-occluded patients from 1.49 +/- 0.89 mV to 2.44 +/- 1.67 mV (p less than 0.005), and in 4 of 6 RCA-occluded patients from 0.66 +/- 0.12 mV to 1.42 +/- 0.52 mV (p less than 0.01). However increased sigma ST in the recanalized group was reduced to the control value existing before recanalization within 30 min after recanalization and continued to decline more rapidly than in the control group. These transient ST segment elevations were not correlated with long-term angiographic determinants of left ventricular function. We conclude that ST segment shows abrupt augmentation after successful thrombolysis and that continuous ST segment monitoring is useful for assessing thrombolysis in AMI.

Adult↗

Thromboxane A2 as an enhancing factor of coronary vasospasticity in variant angina.

To clarify the role of thromboxane A2 (TXA2) in evoking coronary spasm, we compared coronary arterial spasticity induced by ergonovine maleate (EM) with coronary sinus thromboxane B2 (TXB2: a stable catabolite of TXA2) in 34 patients with documented variant angina and 11 patients with chest pain syndrome (CPS). We also examined the effect of OKY-1581 (8 mg/kg, i.v.), a TXA2 synthetase inhibitor, on the coronary arterial spasticity of these patients. When blood samples were taken from coronary sinus just before EM test, all patients with variant angina exhibiting markedly augmented TXB2 levels (424 +/- 138 pg/ml), had positive EM test results, while CPS exhibiting lower TXB2 levels (223 +/- 38 pg/ml), had negative EM test. We found that the amounts of EM needed to induce coronary spasm were inversely correlated with TXB2 levels in coronary sinus. In 7 out of these 8 patients, OKY-1581 was found to attenuate the increased spasticity with reduction of coronary sinus TXB2 levels. In 3 patients, an EM rechallenge at symptomatically quiescent stage resulted in negative test with augmented TXB2 levels being markedly decreased. These findings indicate that increased TXA2 in circulating plasma is closely correlated with the hypersensitivity of coronary arteries to EM in patients with variant angina, suggesting a possible role of augmented TXA2 production in the enhancement of coronary vascular spasticity.

Adult↗