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Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 127 records · Page 7Linked to original sources

Coexpression of cancer-associated carbohydrate antigens, Tn and sialyl Tn.

The expression of cancer-associated antigens, Tn and sialyl Tn, was examined using monoclonal antibodies, MLS 128 and MLS 102, recognizing these two antigens, respectively. A cell lysate from a human carcinoma cell line, LS 180 cells, was analysed by Western blotting using these two antibodies. Three glycoprotein bands were discernible with each antibody, of which two, corresponding to 250 and 210 kDa, were reactive with both the antibodies. LS 180 cells were metabolically labelled with 3H-glucosamine and then the lysate from these cells was applied to two immunoaffinity columns. Sixty-five per cent of the Tn antigenic glycoproteins, based on radioactivity, bound to the MLS 102 affinity column. On the other hand, 45% of the sialyl Tn antigenic glycoproteins bound to the MLS 128 affinity column. These results indicate that some Tn and sialyl Tn antigens were expressed on the same polypeptide chains. The presence of non-sialylated GalNAc residues on the polypeptide chain with many Sia-GalNAc residues appears to be due to the incapability of three consecutive moieties of GalNAc-Ser/Thr to accept sialic acid.

Antigens, Tumor-Associated, Carbohydrate

Expression of sialosyl-Tn antigen (monoclonal antibody MLS102 reactive) in normal tissues and malignant tumors of the digestive tract.

Oncogenic transformation is often associated with changes in the glycosylation state of malignant cells. We investigated the immunohistochemical localization of sialosyl-Tn antigen [O-linked NeuAc(alpha 2-->6)GAINAc] using a novel monoclonal antibody MLS102 in normal and malignant digestive-tract tissues. In normal tissues, weak MLS102 immunoreactivity was observed in the epithelium of the esophagus, stomach and colon. However, MLS102 immunoreactivity was strong in the goblet cells of the duodenum, but not in the Brunner glands. In carcinomas of the esophagus, stomach, colon, pancreas and biliary tract, positive staining was detected with a high frequency (80%-100%). In mucinous carcinomas and signet-ring cell carcinomas, malignant cells themselves and the mucins they secreted were strongly positive for sialosyl-Tn antigen. There was no significant correlation between the frequency of expression of sialosyl-Tn antigen and the degree of differentiation (grade). However, in the case of well-differentiated adenocarcinomas, sialosyl-Tn antigen was found mainly in the supranuclear areas (Golgi area), on the apical surface and in the adjacent cytoplasm. In poorly differentiated adenocarcinomas, the antigen was often detected in the whole plasma membrane and cytoplasm. Therefore, monoclonal antibody MLS102 may be useful in further elucidating the characteristics of digestive-tract cancers, and possibly in their treatment.

Antibodies, Monoclonal

Multiple pulmonary hamartomas: report of a case.

Among lung tumors, multiple hamartomas are uncommon while multiple chondromatous hamartomas are extremely rare, with only 12 cases having been previously reported. A case of multiple pulmonary chondromatous hamartomas in a 58-year-old Japanese man who has been followed up for 28 years is herein presented.

Follow-Up Studies

Dynamic aspects of glutathione metabolism in obstructive jaundice.

The dynamic aspects of glutathione metabolism during obstructive jaundice were analyzed in rats. Plasma bilirubin levels increased after ligation of the bile duct, with a concomitant increase in hepatorenal glutathione levels. When the bile duct was recanalized, plasma bilirubin levels rapidly decreased, with a concomitant decrease in hepatorenal glutathione levels. The half-life of hepatic glutathione turnover increased markedly after bile duct obstruction, returning to normal after recanalization of the bile duct. Intravenous administration of a loading dose of bilirubin inhibited the biliary secretion of glutathione in a dose-dependent manner. On the other hand, renal glutathione efflux increased markedly after bile duct obstruction. These observations suggest that glutathione status is significantly affected in obstructive jaundice, predominantly due to the inhibition of hepatic secretion by increased bilirubin.

Animals

Progression and regression of atherosclerotic findings in the descending thoracic aorta detected by enhanced computed tomography.

Reports evaluating the progression and regression of atherosclerosis by non-invasive procedure are still limited. We investigated the progression and regression of atherosclerotic intimal thickening of the descending thoracic aorta non-invasively measured by enhanced computed tomography in 83 patients (average age 51.0 years) at the beginning and end of a 2.5 year period. The patients were not taking anti-hypertensive, lipid-lowering or hypoglycemic drugs and therefore we consider them as a natural history cohort. At entry, the extent of aortic intimal thickening was 35.2% of the circumference of the cross-section of the wall, which increased to 39.7% after 2.5 years. Spontaneous progression was associated directly with age, elevated levels of total cholesterol, LDL-cholesterol, LDL/HDL cholesterol ratio, diastolic blood pressure, and inversely to HDL-cholesterol. There was little correlation with triglycerides, systolic blood pressure, fasting glucose or body mass index. In 65 of the patients, aortic atherosclerosis progressed, while in 9 patients it remained unchanged, and in a further 9 it regressed. The levels of lipid variables, apart from HDL-cholesterol, and diastolic blood pressure in the patients with spontaneous progression were significantly higher than in the unchanged and spontaneous regression. Thus, this study verified the natural history of aortic atherosclerosis non-invasively measured by enhanced CT.

Adult

Lysine deficient diet and lysine replacement affect food directed operant behavior.

As a test for specific hunger for amino acids with the goal of identifying brain regions which might mediate motivation to alleviate L-lysine (Lys) deficiency, rats were trained to lever press to receive complete diet. Rats were given Lys deficient (Lys-def) diet ad lib. Intraperitoneal (IP) injection of Lys, 2 h before the test session, inhibited lever pressing. Lys injected animals pressed at nearly the same low rate as did animals fed ad lib complete diet, although the response of saline injected animals was also partially decreased. Next, osmotic minipumps were implanted IP and animals given Lys-def diet ad lib. Chronic Lys infusion also strongly inhibited lever pressing. Rats allowed ad lib access to Lys to drink drank significantly more Lys than when given complete diet. Lys chronically infused by minipump into the lateral hypothalamus, also inhibited pressing by rats given Lys-def diet. Therefore, animals lacking Lys in the diet will work to receive complete diet, but replacement of Lys by drinking, chronic IP infusion, or directly into the lateral hypothalamic area inhibits bar pressing behavior.

Animals

Effects of the neuroleptanalgesic fentanyl-fluanisone (Hypnorm) on spike-wave discharges in epileptic rats.

Effects of fentanyl-fluanisone (Hypnorm), a combination often used as a neuroleptanalgesic and anaesthetic, were investigated on spike-wave discharges of epileptic WAG/Rij rats. Fentanyl-fluanisone has stimulating effects on the amount of spike-wave discharges, but not in a dose-dependent manner. A low dose of 0.01 mg/kg fentanyl with 0.5 mg/kg fluanisone causes a large increase in epileptic activity. This effect is larger than with a middle dose of 0.1 mg/kg fentanyl and 5 mg/kg fluanisone and much larger than with a high dose of 0.2 mg/kg fentanyl with 10 mg/kg fluanisone. The last two doses cause a prolonged anaesthetic state in rats. The frequency of the spikes in the spike-wave discharges was decreased by the mixture of fentanyl-fluanisone; this decrease was dose-dependent. Administration of fentanyl alone in the same doses as in the combination abolishes spike-wave activity during the anaesthetic phase but causes a moderate increase after this phase. It also causes a lowering in spike frequency, which is of the same order as with fentanyl-fluanisone. The mechanisms of action of fentanyl are not completely clear, but the opposite effects of mu- and kappa-opioid receptors on spike-wave discharges may play a role in this biphasic effect. Fluanisone alone in the same doses as in the mixture induces a large dose-dependent increase in spike-wave activity, with only a small effect on spike frequency. This might be caused by the antagonistic action of this drug at dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of successful angioplasty following thrombolysis on infarct size and left ventricular function.

The role of the angioplasty following thrombolysis in acute myocardial infarction has been discussed in several studies, however the effect of successful angioplasty on infarct size and left ventricular function has not been properly evaluated. Successful reperfusion was achieved in 79 out of 104 patients with primary anterior acute myocardial infarction. These patients were classified as follows, according to the type of intervention during the acute phase: 50 patients in which thrombolysis was successful (the thrombolysis group); 12 patients who underwent successful immediate angioplasty following successful thrombolysis (the immediate angioplasty group); and 17 patients in which rescue angioplasty was successful (the rescue angioplasty group). The 25 patients whose infarct-related vessels were not reperfused after intervention were classified as the non-reperfused group. Infarct size, evaluated as defect volume by T1-201 SPECT, 1 month after the onset, was 840 +/- 154 units (mean +/- S.D.) in the immediate angioplasty group and was similar to that in the thrombolysis group (948 +/- 88 units), but significantly smaller than in the non-reperfused group (1759 +/- 108 units). There were no significant differences in left ventricular function in the immediate angioplasty group and the thrombolysis group. Successful rescue angioplasty did not have any beneficial effect on left ventricular functions or infarct size, when compared with the failed thrombolytic group (1105 +/- 169 units vs. 1617 +/- 169 units). End-diastolic volume (52 +/- 3 ml/m2) in the successful rescue angioplasty group, however, was significantly smaller than in the failed thrombolysis group (67 +/- 3 ml/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The effect of prostaglandin E1.alpha CD on vibratory threshold determined with the SMV-5 vibrometer in patients with diabetic neuropathy.

We studied the effect of prostaglandin E1.alpha CD (PGE1) on diabetic peripheral neuropathy by evaluating subjective symptoms and vibration sensation using a new vibrometer (SMV-5). Patients with diabetic neuropathy (n = 38) were divided into three groups; group A received no drugs (control), group B was treated with 1500 micrograms/day of oral methyl vitamin B12 (VB12) for four weeks, and group C received 1.2 micrograms/kg/day PGE1 intravenously for four weeks. There was a close relationship between symptom scores and vibratory threshold (VT). The effect of PGE1 on subjective symptoms and VT were compared with those in groups A and B. Patients who received PGE1 showed a significant improvement rate in pain and hypesthesia compared to patients in groups A and B, and in numbness compared to group A. During the study period, there was no significant change in VT in groups A and B, whereas VT was significantly improved at styloid process (P < 0.05) and at medial malleolus (P < 0.001) in group C. Our results confirmed that PGE1 significantly improved both subjective symptoms and VT, indicating that PGE1 therapy may be useful in diabetic neuropathy.

Administration, Oral

Recombinant human granulocyte colony-stimulating factor augments cytotoxicity of OK-432-induced polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMNs) recovered from the peritoneal cavity of mice treated with the streptococcal preparation OK-432, exhibited strong cytotoxicity after the in vitro addition of Nocardia rubra cell wall skeleton (N-CWS). In this study, we investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could augment the cytotoxicity of OK-432-induced PMNs after the addition of N-CWS in vitro. PMNs recovered from the peritoneal cavity of 8- to 10-week-old, male C3H/He mice induced by intraperitoneal (i.p.) injection of 50 KE/kg (1 KE = 0.1 mg) of OK-432 were used in a 51Cr release assay against MM46 mammary carcinoma cells. While addition of rhG-CSF in vitro did not augment the cytotoxicity of OK-432-induced PMNs, marked augmentation of the cytotoxicity of OK-432-induced PMNs was observed following a single subcutaneous (s.c.) or i.p. injection of 125 micrograms/kg of rhG-CSF. The effect of in vivo administered rhG-CSF was dependent on the timing of the injection with respect to OK-432 administration and differed from s.c. or i.p. injections. Interestingly, the cytotoxicity of OK-432-induced PMNs was rather weak following consecutive s.c. or i.p. administration of rhG-CSF for 7-14 days. H2O2 is likely involved in mediating the cytotoxicity of OK-432-induced PMNs since activity was significantly reduced by the in vitro addition of low concentration of catalase. Generation of H2O2 by the PMNs correlated with cytotoxicity. These results suggest that in vivo administration of rhG-CSF augments the cytotoxicity of OK-432-induced PMNs in a time dependent fashion and that H2O2 plays an important role in mediating their cytotoxicity.

Animals

A new nonionic macrocyclic gadolinium(III) chelate as a potential magnetic-resonance-imaging contrast agent.

A new GdIII complex of a 17-membered macrocycle with three pendant carboxymethyl groups has been synthesized; the ligand has been obtained in a single step from diethylenetriaminepentaacetic dianhydride (pentetic dianhydride) and 1,4-butanediamine (putrescine). An X-ray crystal analysis has shown that the complex is a nonionic metal chelate with a coordinated water molecule. The near-zero electrical conductivity, 1 omega-1 cm2 mol-1, of a 1 mM solution indicated that the metal chelate is essentially undissociated. The NMR T1 relaxivity is 2.5 s-1 mM-1 at a resonance field of 64 MHz, and 3.4 s-1 mM-1 at 250 MHz. This new GdIII complex is a potentially important magnetic resonance imaging contrast agent.

Chelating Agents

Progressive decreases in coronary vein flow during reperfusion in acute myocardial infarction: clinical documentation of the no reflow phenomenon after successful thrombolysis.

OBJECTIVES: This study was undertaken to examine the effects of coronary flow dynamics after thrombolysis on infarct size limitation. BACKGROUND: It has been commonly accepted that early thrombolysis does not necessarily salvage infarcted myocardium. Plausible causes for myocardial necrosis include such factors as elapsed time to reperfusion, residual stenosis, collateral vessels, hemodynamic loads, preconditioning and reperfusion injury. Recently, the no reflow phenomenon has been elucidated to be associated with infarct extension in clinical studies employing contrast echocardiography or thallium scintigraphy. METHODS: Nineteen patients with early reperfusion in acute anterior myocardial infarction and comparable clinical background were studied. The patients were classified into two groups on the basis of pattern of thermodilution measurements of great cardiac vein flow after reperfusion: group A, 9 patients with a progressive decrease in great cardiac vein flow during the 1st 24 h of the onset of infarction; and group B, 10 patients without this observation. Left ventricular ejection fraction and thallium perfusion defect were compared between the two groups at follow-up. RESULTS: There were no significant differences in systemic hemodynamic variables between groups A and B, and neither group had recurrent ischemic events suggesting reocclusion or restenosis during the study. In group A, both great cardiac vein flow (mean +/- SD 44 +/- 17% reduction) and oxygen extraction (38 +/- 15% reduction) were progressively decreased after the onset of reperfusion. Compared with group B, this group showed a lower left ventricular ejection fraction (36 +/- 7% vs. 63 +/- 15%, p < 0.01) and a larger thallium-201 defect severity index (1,091 +/- 366 U vs. 247 +/- 261 U, p < 0.01) at follow-up. Although other patient characteristics were comparable between the two groups, antecedent angina occurred in 90% of group B patients in contrast to only 33% of group A patients. CONCLUSIONS: Salvage of myocardium from infarction by successful thrombolysis was not observed in the patients demonstrating progressive decreases in great cardiac vein flow (group A). In those patients, inadequate myocardial reperfusion on a microvascular basis might be associated with a much larger myocardial infarction. Antecedent angina may protect against a progressive decrease in coronary flow and may have beneficial effects on infarct size limitation.

Adult

Analysis of transmural trend of myocardial integrated ultrasound backscatter for differentiation of hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension.

OBJECTIVES: This study was undertaken to differentiate hypertrophic cardiomyopathy from hypertensive hypertrophy using a newly developed M-mode format integrated backscatter imaging system capable of calibrating myocardial integrated backscatter with the power of Doppler signals from the blood. BACKGROUND: Myocardial integrated ultrasound backscatter changes in patients with hypertrophic cardiomyopathy; however, it is unknown whether ultrasound myocardial tissue characterization may be useful in differentiating hypertrophic cardiomyopathy from hypertensive hypertrophy. METHODS: Calibrated myocardial integrated backscatter and its transmural gradient were measured in the septum and posterior wall in 31 normal subjects, 13 patients with hypertensive hypertrophy and 22 patients with hypertrophic cardiomyopathy. The gradient in integrated backscatter was determined as the ratio of calibrated integrated backscatter in the endocardial half to that in the epicardial half of the myocardium. RESULTS: Cyclic variation of integrated backscatter was smaller and calibrated myocardial integrated backscatter higher in patients with hypertrophied hearts than in normal subjects, but there were no significant differences in either integrated backscatter measure between patients with hypertensive hypertrophy and those with hypertrophic cardiomyopathy. Transmural gradient in myocardial integrated backscatter was present only in patients with hypertrophic cardiomyopathy (5.0 +/- 1.8 dB [mean +/- SD] for the septum; 1.2 +/- 1.6 dB for the posterior wall). CONCLUSIONS: Hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension can be differentiated on the basis of quantitative analysis of the transmural gradient in integrated backscatter.

Acoustics

Case-control studies: matched controls or all available controls?

In order to realize the variation in the estimate of the odds ratio from case-control studies, results from individually matched sampling were compared with those from the analysis based on a large number of controls. The subjects were selected from those who visited Aichi Cancer Center Hospital from 1988 to 1990. Cases consisted of 251 male lung cancer patients aged 40-79 years. Age and year of visit matched controls were sampled independently 100 times and 5000 times from non-cancer male outpatients (cases to controls ratio: 1:1, 1:2, 1:3, and 1:4). As unmatched controls, all male non-cancer outpatients aged 40-79 years (4100 patients) were used. The smoking habit was adopted as an exposure variable. As logically expected, analysis based on 4100 male controls gave a steadier estimate than the matched analyses examined here, indicating that a matched sampling is not recommended when a large number of controls are available.

Adult

Malignant schwannoma in a case of type 1 neurofibromatosis with decreased immunoreactivity of smooth muscle alpha-actin in tumor vessels.

A malignant schwannoma in the left calf of a 37-year-old man with type 1 neurofibromatosis is herein reported. Since it is known that capillaries in benign neurofibromas are accompanied by hypertrophic pericytes expressing an abundant amount of smooth muscle alpha-actin (SMAA), we examined the immunohistochemical reactivity of SMAA within this malignant tumor and then compared it with that in surrounding benign areas. In the nests of malignant cells, decreased SMAA staining was found in the capillary walls. In the benign tissues around the malignant tumor, various extents of SMAA could be visualized in the vessels and myofibroblasts. Platelet-derived growth factor (PDGF) was also detected in the tumor, suggesting that cytokines secreted by malignant cells may have an influence on the expression of SMAA as well as on the alteration of the structure of blood vessels.

Actins

Immunohistochemical demonstration of tenascin and fibronectin in odontogenic tumours and human fetal tooth germs.

The distribution of tenascin and fibronectin (plasma fibronectin) was studied immunohistochemically in ameloblastomas, ameloblastic fibromas and ameloblastic carcinomas, as well as in tooth germs using monoclonal antibodies. Tenascin is an extracellular matrix molecule that was shown to be enriched in the embryonic mesenchyme surrounding the budding epithelium in various organs, including the tooth. Tenascin was strongly expressed in the basement membrane zone of the ameloblastomas and in the early tooth germ and the dental lamina, but not in the dental follicle. The expression of tenascin in the ameloblastic fibroma was seen in the basement membrane of the epithelial islands throughout the stromal tissues. There were clear differences in fibronectin expression in the follicular ameloblastoma and ameloblastic carcinoma. The results suggest that tenascin and fibronectin are involved in epithelial mesenchymal interactions of the tooth germ and in odontogenic tumours.

Ameloblastoma