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Biomedical subjects

K Misawa

Publications and source records attributed to K Misawa.

At least 73 records · Page 4Linked to original sources

[Problem of the long-term arterial infusion therapy with implantable reservoir for unresectable hepatocellular carcinoma].

Arterial infusion therapy with implantable reservoir was performed for forty-seven cases with unresectable hepatocellular carcinoma since 1986-1991. The one-year survival rate of cases of arterial infusion therapy with implantable reservoir was 50.6% and the 2-year survival rate was 37.8%. The survival rate was 51.4% and 32.2%, respectively, in the TAE cases for the same period. Considering the kinds of reservoirs used for HCC, the survival curve of 23 cases with double lumen reservoir showed a significantly better pattern than that of 24 cases with the usual single lumen reservoir (p less than 0.05). Cumulative usable rate of reservoir was 78.6% at one year, and 42.4% at two years (Kaplan-Meier method). Therapy after the reservoir was unusable, particularly with arterial obstruction by catheter, was restricted because arterial infusion therapy was impossible. It is considered very important to retain the hepatic artery because arterial infusion therapy is mainly for unresectable hepatocellular carcinoma.

Antineoplastic Agents↗

[A case of small cell undifferentiated carcinoma (SCUC) of the rectum treated with etoposide, cis-platinum and radiotherapy].

A 29-year-old-woman with recurrent cancer of rectum was treated with Etoposide, cis-platinum and external irradiation. Previous postoperative chemotherapies consisted of MMC, CPA, VCR and HCFU. Histologically, the tumor invaded in sheets and nests, and consisted of round to ovoid malignant cells with high nuclear/cytoplasmic and hyperchromatic nuclei with a coarse, clumped, or stippled chromatin pattern. Most cells demonstrated a positive reaction by Grimelius and NSE staining. Eight months after surgery, we switched to Etoposide cis-platinum and external irradiation, because of local recurrence. Etoposide (total 725 mg) and cis-platinum (total 100 mg) were injected into bilateral iliac artery and 60 Gy radiotherapy was performed. The patient showed a good response, and a complete response (CR) was evident for the following 42 months. Thus, Etoposide, Cis-platinum and radiotherapy are considered an effective combination therapy for a patient with small cell undifferentiated carcinoma.

Adult↗

[Coronary artery spasm immediately after the long-standing operation for cancer of the tongue].

A 72-year-old male underwent radical operation for cancer of the tongue. Anesthesia was maintained with the combination of enflurane-N2O-vecuronium and cervical epidural block. Five minutes after the cessation of the longstanding operation, VT and circulatory collapse occurred. After administration of lidocaine and ephedrine, VPC and ST elevation were noted, followed by VT and Vf. Cardioversion successfully restored sinus rhythm with no ST change, suggesting an episode of coronary artery spasm. The possible inducing factors in this case were hypotension and acute imbalance in autonomic nervous systems caused by hypovolemia, hypothermia, insufficient anesthetic depth, loss of surgical stress, neostigmine and epidural block. The authors reviewed case reports on coronary spasm, especially looking for possible inducing factors of coronary artery spasm during anesthesia.

Aged↗

Characterization of antibodies to advanced glycosylation end products on protein.

Antibodies directed against advanced glycosylation end products (AGEs) formed during a Maillard reaction have been generated and characterized. Since protein-bound AGEs recognized by the antibodies were labile to acid hydrolysis, the antibodies were further characterized by using the AGE-alpha-acetyl-L-lysine methyl ester (AGE-ALME) with a brown and fluorescent property as well as the AGE-proteins. The antibodies reacted with fluorescent compounds, rather than brown pigment compounds, in the AGE-ALME. The fluorescent compounds in the AGE-ALME were separated into four fluorescent compounds by reversed-phase thin layer chromatography (TLC). Of the fluorescent compounds tested, compound 3 (Rf = 0.63), as designated on a TLC plate, showed the highest affinity for the antibodies. In addition, the antibody recognition to the cross-linked oligomers with fluorescence in the AGE-protein was investigated by using bovine pancreatic ribonuclease A (RNase), which is known as a model protein for studying AGE-induced cross-linking. Fluorescence in the AGE-RNase existed in both of the oligomers and the monomer. The cross-linked oligomers exhibited higher affinity to the antibodies than did the monomer, which has a similar degree of fluorescent intensity. These results indicate that our antibodies against cross-linked protein-bound AGEs may serve as a useful tool to elucidate pathophysiological roles of advanced Maillard reaction in diabetic complications and aging processes.

Antibodies↗

Radioimmunoassay for the determination of glycated haemoglobin.

A competitive radioimmunoassay for the quantitative determination of glycated haemoglobin was developed. The antiserum, obtained by immunizing guinea pigs with reduced glycated human albumin, was capable of identifying and quantitating the glucitollysine residues of glycated Hb after reduction with sodium borohydride. To simplify the sample preparation we introduced trichloroacetic acid precipitation to remove unreacted sodium borohydride instead of using dialysis or gel filtration. Using this procedure, our radioimmunoassay became relatively simple and provided satisfactory within- and between-run (1.3-2.8% and 1.9-5.4% coefficient of variation, respectively). The radioimmunoassay method was compared to the measurement of HbAlc by high performance liquid chromatography which is the most widely used method for quantitating glycated Hb. For this purpose glycated Hb was measured in normal glucose tolerance, impaired glucose tolerance, and diabetes mellitus groups based on WHO criteria. Both assays were able to discriminate between the normal and diabetic groups. In addition, while the determination of glycated Hb by the radioimmunoassay method was able to clearly discriminate between the normal and impaired glucose tolerance groups, the determination of HbAlc by the high performance liquid chromatography method failed to discriminate between these two groups. Moreover, 15 of the 20 impaired glucose tolerance patients exceeded the upper normal range (mean normal values + 2 SD) in radioimmunoassay. But all 20 patients with impaired glucose tolerance were within the upper normal range in HbAlc values. These results demonstrate that the measurement of glycated Hb by radioimmunoassay is more sensitive than the measurement of HbAlc by high performance liquid chromatography since it can discriminate between the normal and impaired glucose tolerance groups.

Adult↗

Guanine levels in house dust as a means of estimating the mite population.

House dust has recently been incriminated as an important causative allergen in bronchial asthma and allergic rhinitis. In particular attention is being focused on the mites contained in house dust. Previously, the number of mites contained in house dust was determined by counting under a microscope. This method is not appropriate, however, for epidemiological investigations which require large numbers of specimens, as it is time-consuming and labor intensive. Guanine makes up about 0.3% of the body weight of mites and is present in large amounts in mite excrement, and by using an improved method for quantifying guanine in house dust we obtained a correlation coefficient of 0.776 between the number of mites and amount of guanine. In addition, because virtually no guanine is contained in human nails and hair, thus eliminating possible sources of error, it became clear that the amount of guanine in house dust can be used to estimate the total amount of mite allergen resulting from the bodies and excrement of the acarids.

Animals↗

Production and characterization of antibodies to advanced glycation products on proteins.

Antibodies directed against advanced glycation products formed during Maillard reaction have been generated and characterized. These antibodies reacted specifically with advanced glycation products in common among proteins incubated with glucose, but not early-stage compounds such as a Schiff base adduct and Amadori rearrangement products. Incubation of bovine serum albumin with glucose caused a time-related increase in immunoreactivity and a concomitant increase in fluorescence intensity. These antibodies may serve as a useful tool to elucidate pathophysiological roles of advanced Maillard reaction in diabetic complications and aging processes.

Antibodies↗

Radioimmunoassay for non-enzymatically glycated serum proteins.

We have developed a radioimmunoassay (RIA) for nonenzymatically glycated serum proteins. The polyclonal antibodies prepared against reduced glycated human albumin were specific for the glucitollysine residues of serum proteins. Serum proteins from diabetic patients (n = 25) contained 5.3 +/- 2.8 nmoles of glucitollysine/mg protein, compared to 2.0 +/- 0.2 in controls (n = 20). The intra- and inter-assay variables were 3.2-6.2% and 4.4-8.6%, respectively. Results from this assay procedure correlated well with those from the boronate affinity chromatography procedure (r = 0.94; P less than 0.001). The data suggested that diabetic serum proteins contained at least 2.5 times as much immunochemically detectable glucitollysine residures as normal serum proteins after reduction of the proteins with sodium borohydride.

Adult↗

[An epidemiological study on the relationships among HDL-cholesterol, smoking and obesity].

The relationships among high-density lipoprotein cholesterol (HDL-C) and other serum lipid items, and active smoking, passive smoking, obesity, alcohol drinking and working status were investigated. This study was performed both in healthy adults and in schoolchildren. The adult group was sampled at random from those who were diagnosed to be healthy by medical examination at the Automated Multiphasic Health Testing and Services Center in Tokai University Hospital, and the schoolchildren group was selected with regular health examinations in a primary school in Tokyo. In the case of adults, it was found that the greater the value of triglyceride (TG), the greater the number of cigarettes smoked. On the other hand, HDL-C decreased with increasing cigarette smoking. Obesity level increased with increasing values of TG, total cholesterol (TC) and low density lipoprotein (LDL-C) but in the case of HDL-C, the value decreased. Alcohol drinking made the HDL-C level increase. Although the HDL-C level increased slightly with obesity, the relationship between HDL-C and passive smoking was not clear in the case of schoolchildren.

Adult↗

Resistance oscillation of a Millipore DOPH model membrane accompanying structural changes.

A Millipore DOPH model membrane is composed of a Millipore filter whose pores are filled with dioleylphosphate (DOPH), and its electric resistance increases by a factor of 10(4) when Ca2+ ions are combined with it. The concentration of CaCl2 which increases the membrane resistance depends on the density of DOPH adsorbed in the filter and the initial KCl concentration. The surface structure of the membrane changes at the same time as the membrane resistance increases. The structural changes can be directly observed by a stereoscopic microscope: a considerable decrease of the hydrophilic regions of the membrane is caused by the Ca2+ ions. The membrane resistance which become higher with Ca2+ ions oscillates while a constant current and a static pressure stimuli are applied to the membrane. The frequency is dependent of these stimuli. These stimuli change the local membrane surface structure to make the hydrophilic areas. It is conceivable that the structural changes are caused by replacing Ca2+ ions with K+ ions in the hydrophilic bases of DOPH molecules.

Calcium↗

Calcium ion concentration detected by structural changes of a Millipore DOPH artificial membrane.

The surface structure of an artificial membrane composed of a Millipore filter and a synthetic lipid analogue, dioleylphosphate (DOPH), immersed in KCl solution changes when the CaCl2 concentration reaches a critical value. Using a photomultiplier mounted on the eyepiece of a stereoscopic microscope the structural change can be measured quantitatively as an intensity variation of reflected light of the membrane surface. Calcium ions decreased the intensity to about 50% of the original hydrophilic state whose solution was only KCl. However, the degree of structure change was dependent on adsorbed DOPH density, solution temperature and pH value. On the other hand, using the light reflectance curves obtained from the structural observations, an unknown CaCl2 concentration in a KCl solution can be determined. Since the reflectance curve shifts widely with various densities of DOPH adsorbed in the Millipore filter, it is possible to measure the CaCl2 concentration over a wide range. The detection range was from 0.1 to 50 mM CaCl2.

Adsorption↗

The effect of abstinence from smoking on urinary excretion of hydroxyproline.

The effect of abstinence from smoking on the urinary hydroxyproline to creatinine ratio (HOP ratio) was assessed in 49 smokers who participated in an anti-smoking course. Urine samples were collected at the beginning of the course and weekly during the subsequent 14 weeks in 1985. The subjects were divided into five groups depending on the number of cigarettes smoked daily before abstinence: 1-10, 11-20, 21-30, 31-40 and greater than 40 cigarettes. The urinary HOP ratio immediately after abstinence from smoking was proportional to the mean daily number of cigarettes smoked in the past. All groups showed decreasing HOP ratios with a longer period of abstinence. Half of the total decrease observed in the HOP ratios after 14 weeks was reached within 5 or 6 weeks. When using the Brinkman index to adjust for the number of smoking years, half of the maximum decrease in all groups was reached within 4 weeks. In an exponential decay model fitted to the data, the half-life time taken to reach the non-smokers' level was 9-10 weeks for all groups. The HOP level of smokers who smoked less than 41 cigarettes before cessation approached the HOP level of the control group after 61-74 weeks. The results suggested that the urinary HOP ratio was useful as a biochemical marker for short-term breakdown of lung collagen and lung elastin.

Biomarkers↗

[Reservoir implanted arterial infusion therapy in liver cancer with replaced right hepatic artery].

Seven cases of liver cancer with replaced right hepatic artery were treated with arterial infusion therapy using implanted reservoir. The reservoir was surgically implanted in all cases. In 5 cases, right hepatic artery ligation was done simultaneously. TAE via right hepatic artery and ligation of middle and left hepatic artery was done in 2 other cases. ADM, CDDP, MMC, 5-FU and Lentinan were used. As the result, decrease in tumor size or necrosis of tumor was found in 3 cases of hepatomas, necrosis of tumor was found in 1 of three cases of metastatic liver cancer and remarkable decrease in tumor size and normalization of CEA level were found in another case. Arterial infusion therapy using implanted reservoir for the cases with variation would be effective with the combination of hepatic ligation or TAE.

Aged↗

[Study on the pharmacokinetics of UFT in patients with hepatocellular carcinoma associated with cirrhosis].

UFT was administered preoperatively in 20 cases of primary hepatocellular carcinoma, and tegafur, 5-fluorouracil (5-FU), uracil, total thymidylate synthase (TS) and free TS in blood and liver tissue were determined. The results were as follows. 1. Tegafur level was significantly high in blood, while the levels of 5-FU and uracil were high in the liver tissue. The 5-FU level in the cancerous area was 0.099 micrograms/g, higher than the effective level regardless of the presence or not of complication with liver cirrhosis. 2. Total TS, FdUMP (computed as total TS-free TS) and TS inhibition rate [(computed as (TS-free TS)/TS x 100 (%)] were significantly higher in the cancerous liver tissue than in the non-cancerous area. In the cases where determination was made simultaneously for the cancerous liver and non-cancerous liver tissues, the FdUMP level and TS inhibition rate in the cancerous liver tissue were high in 14 out of 17 cases (82.4%) and 13 out of 17 cases (76.5%) respectively. Therefore, UFT seems to have selective toxicity. 3. No correlation was found between 5-FU level, total TS, FdUMP in the liver tissue on the one hand and TS inhibition rate on the other. 4. UFT yielded sufficient 5-FU levels in the cancerous area regardless of the presence or not of complication with cirrhosis and therefore is expected to inhibit DNA synthesis selectively in the cancerous tissue.

Adult↗

[Studies on the absorption kinetics of subcutaneously administered insulin].

This study was designed to evaluate, using compartmental model analysis, the effects of jet injection, changes in injected dosage, and mixture of short- and intermediate-acting insulin preparations on the absorption kinetics of human insulin (HI) mainly in rabbits. The following results were obtained. (1) It was found that a split-pool model was adequate for the evaluation of the absorption kinetics of insulin. (2) Jet injection resulted in more rapid absorption of insulin than needle injection. Since parameter K12 (inter-pool rate constant) of jet injection was three times as large as that of needle injection, the accelerated absorption by jet injector could result from the rapid movement of insulin from the injection site to the absorption site. (3) A negative correlation between insulin dosage and Kd (degradation rate constant) was observed, suggesting that the process of subcutaneous absorption of insulin includes a nonlinear component. (4) The prompt injection of Actrapid HI mixed with Monotard HI in a single syringe caused a delayed absorption of Actrapid HI. In contrast, there was no prolonged absorption after the injection of regular HI mixed with NPH-HI in a single syringe. There was a significant positive correlation between the percent change of K12 (in separate injection and mixed injection) in vivo and the recovery rate of short-acting insulin when mixed with intermediate-acting insulin in vitro. In clinical studies of diabetic subjects, higher serum free insulin levels before noon and higher K12 values were observed after the mixed injection of regular HI and NPH-HI, compared with that of Actrapid HI and Monotard HI. These results suggest that the application of compartmental model analysis is useful to studying the absorption kinetics of subcutaneously injected insulin.

Adult↗

A radioimmunoassay for an advanced glycosylation endproduct.

A competitive radioimmunoassay for an advanced glycosylation endproduct, 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI) was developed. The immunogen was prepared by coupling of 4-furanyl-2-furoyl-1H-imidazole-1-hexanoic acid to keyhole limpet hemocyanin. The antiserum obtained by immunizing guinea pigs with the immunogen exhibited high affinity binding to FFI, but no cross-reactivity was observed for structurally related compounds containing an imidazole ring or furan ring(s). By using the radioimmunoassay, the levels of FFI in bovine serum albumin incubated with glucose for varying lengths of time were measured. A time-dependent increase was obtained in the amount of acid-liberated FFI and fluorescence. The radioimmunoassay described here had satisfactory reproducibility as judged by the intra-assay precision of 3.4-6.4% and the interassay precision of 7.3-8.9%. The method allows to quantitate FFI on the modified proteins that have been implicated in the complications of diabetes and in normal aging as well.

Animals↗

[Fabrication and clinical application of intrahepatic arterial catheter facilitating repeated infusion therapy and experience].

Balloon occluded arterial infusion (BOAI) is an ideal and widely accepted method for augmentation of the intrahepatic tissue level of anticancer drugs. But this method nakes repeated infusion very difficult because the Seldinger method is needed to cannulate into the hepatic artery. Recently, we made an intrahepatic artery catheter attached with an implantable reservoir, consisting of an intra-arterial catheter, reservoir and cylinder-like device which has a small balloon on its inner part. The cannulation is done at laparotomy. With this method, five cases of nonresectable hepatocellular carcinoma, one metastatic liver cancer and one noncurative hepatocellular carcinoma were treated. Intrahepatic vessels were quite visible by DSA using CO2 gas. Serum concentration level of adriamycin was lower and undetectable at 120 minutes after infusion. No side effects nor catheter complications were observed. Intra-arterial infusion therapy using this device will be a most useful routine method for cancer control in the outpatient clinic.

Aged↗