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M Kodama

Publications and source records attributed to M Kodama.

At least 325 records · Page 18Linked to original sources

Induction of antitumor activities in spleen cells from mice and rats activated with lipopolysaccharide immobilized on beads.

Lipopolysaccharides (LPS) were coupled to polystyrene beads in order to apply the LPS without toxicity. The antitumor activity of the LPS-immobilizing beads was studied in experiments in vitro and in vivo. In vitro studies showed that spleen cells from C3H/HeN mice stimulated by beads immobilizing LPS from Escherichia coli produced cytolytic activity as strong as that of lymphokine-activated killer (LAK) cells. Spleen cells from Sprague-Dawley rats stimulated by beads immobilizing LPS from Salmonella minnesota produced cytolytic activity stronger than that of LAK cells. However, spleen cells stimulated by beads immobilizing each component of the LPS separately could not induce cytolysis. Contact stimulation, even for a brief period, sufficed for cytolytic activity, and was enhanced by culture for 48-72 h. Through in vivo studies, the suppression of tumor growth and a prolongation of the survival time were observed in tumor-bearing mice injected with spleen cells activated by beads immobilizing LPS from E. coli, and in mice injected with LAK cells. The effect of the activated spleen cells was stronger than that of the LAK cells. In rats bearing metastatic tumors, spleen cells activated by beads immobilizing LPS from S. minnesota suppressed lung metastases more strongly than did LAK cells. These findings indicate that LPS immobilized by beads induced killer cells more strongly than interleukin-2. Ex vivo immunomodulation with LPS-immobilizing beads can be applied usefully as an anticancer treatment.

Animals↗

An immunosuppressant compound, FK-506, prevents the progression of autoimmune myocarditis in rats.

A new immunosuppressive compound, FK-506, is a macrolide produced by Streptomyces tsukubaensis. It is reported that FK-506 prolongs the viability of allogenic grafts of the heart and kidney in vivo and inhibits the development of autoimmune diseases. Furthermore, immunosuppressive therapy of myocarditis in humans has been given special attention by various observers; however, it is controversial. This study investigates the effects of FK-506 on experimental autoimmune myocarditis in rats. We performed two experiments. In Experiment 1, FK-506 was given intramuscularly on Days 11-20 after the first immunization. The rats were immunized twice (on Day 0 and Day 7). They were injected subcutaneously in the footpads with 1.0 mg of human cardiac myosin in equal volumes of complete Freund's adjuvant supplemented with Mycobacterium tuberculosis. They were divided into four groups: Control (six rats, saline), group 1 (six rats, FK-506: 0.1 mg/kg/day), group 2 (seven rats, FK-506: 0.32 mg/kg/day), and group 3 (six rats, FK-506: 1.0 mg/kg/day). To investigate the histologic extent of myocarditis, we formulated a histologic score (0-3). Histologic scores were: Control, 1.90 +/- 0.14; group 1, 0.97 +/- 0.46; group 2, 0.03 +/- 0.05; and group 3, 0 +/- 0. The indices of heart weight/body weight were: Control, 0.74 +/- 0.10%; group 1, 0.45 +/- 0.05%; group 2, 0.35 +/- 0.03%; and group 3, 0.35 +/- 0.03%. In Experiment 2, FK-506 was given on Days 1-10 after the first immunization, earlier than in Experiment 1. The rats were similarly divided into four groups. Each group was given the same dose of FK-506 as in Experiment 1. Histologic scores were: Control 1.49 +/- 0.24; group 1, 1.60 +/- 0.22; group 2, 0.29 +/- 0.41; and group 3, 0.03 +/- 0.03. The indices of heart weight/body weight were: Control, 0.69 +/- 0.15%; group 1, 0.76 +/- 0.09%; group 2, 0.42 +/- 0.08%; and group 3, 0.37 +/- 0.03%. Accordingly, in Experiments 1 and 2, the effects of FK-506 on autoimmune myocarditis were dose-dependent. On the other hand, in Experiments 1 and 2, not only in the control group but also in all treated groups, the titers of anti-myosin IgG were high. In conclusion, even if it is administered just before the onset of myocarditis, FK-506 is extremely effective at suppressing autoimmune myocarditis, despite a high titer of anti-myosin IgG.

Animals↗

Study of blood compatible polymers. II. poly(N,N-disubstituted) acrylamides.

Poly(N,N-disubstituted) acrylamides with both hydrophilic and hydrophobic groups as substituents were synthesized. Different degrees of hydrophilicity were achieved by varying the bulk of the hydrophobic substituent. N-alkyl, N-(2-hydroxyethyl) acrylamides with alkyl substituents propyl (PROPAAm), octyl (OCTAAm) and benzyl (BENAAm) were synthesized. The swelling capacity of the polymers decreased with increase in bulk of the hydrophobic substituent. In vitro studies showed that the surfaces of these polymers did not induce platelet aggregation. Cell compatibility of these polymers was assessed by following the growth of human umbilical cord fibroblast cells. Pronounced cell growth and spreading was observed on the surfaces of polyOCTAAm and polyBENAAm. The relatively low cell growth on polyPROPAAm was ascribed to its high water content.

Acrylamides↗

Comparison of imaging methods for localization of parathyroid tumors.

Preoperative localization of parathyroid tumors by computed tomography (CT), thallium-201/technetium-99m pertechnetate subtraction scintigraphy (Tl-201/Tc-99m), ultrasonography (US), and magnetic resonance imaging (MRI) was compared in patients with hyperparathyroidism (HPT) to examine the characteristics of each method. A total of 87 patients with HPT were divided into two groups according to the time when they were examined. Patients in group I were examined before MRI had been introduced in our hospital, and a 2.5-MHz transducer probe was used for US. Those in group II were examined by MRI and US using a 7.5-MHz transducer probe. Group I included 45 patients (36 with primary hyperparathyroidism [PHPT] and 9 with secondary hyperparathyroidism [SHPT]), and group II included 42 patients (15 with PHPT and 27 with SHPT). In both PHPT and SHPT and SHPT of group I and PHPT of group II, there was no significant difference in detection rates between all diagnostic methods. In patients with SHPT in group II, the detection rate was significantly higher for CT than for Tl-201/Tc-99m and MRI (both p less than 0.01), and for US than for Tl-201/Tc-99m (p less than 0.01). In both groups I and II, the detection rate of each study method was significantly higher in patients with PHPT than in those with SHPT (all p less than 0.01). Compared with group I, the rate was significantly improved in group II, in both types of patients. Regarding the location of the parathyroid tumor, the detection rate of CT was significantly higher for upper parathyroid glands than for lower glands, whereas that of US and Tl-201/Tc-99m was significantly higher for lower glands. The detection rate sharply increased when the tumor weight reached 250 mg (CT, US) or 1,000 mg (Tl-201/Tc-99m, MRI).

Adult↗

Assessment of upper and lower extremity movements in hemiplegic children.

Upper and lower extremity movements were assessed in 26 children with spastic hemiplegia according to the modified Brunnstrom method. Of the upper extremity movements, supinating the forearm was most difficult, followed in order by pronating the forearm, flexing the shoulder to 90 degrees, flexing the shoulder to 180 degrees, abducting the shoulder to 90 degrees or putting the hand on the lumbar spine, putting the hand behind the ipsilateral ear (flexor synergy), and putting the hand on the contralateral knee (extensor synergy). The extensor and flexor synergies were easier than the other movements in the hemiplegic children as well as in hemiplegic adults, but the order of difficulty in the other movements in children was not the same as in adults. The difficulty in the lower extremity movements was uniform in the subjects. None of the children could dorsi-flex the ankles and many could not rotate the hips internally. A small number of the children could not flex the knees or perform straight leg raising. All children could flex the hips and knees, extend the hips and knees, and abduct the hips. The difficulty in isolated hip abduction and flexion was less prominent in the hemiplegic children, compared to in hemiplegic adults.

Adolescent↗

Immunohistochemical characterization of infiltrating mononuclear cells in the rat heart with experimental autoimmune giant cell myocarditis.

The pathogenesis of giant cell myocarditis remains unclear. Subsets of inflammatory infiltrating cells may reflect the pathogenesis and etiology of the disease. Therefore, we examined subsets of infiltrating mononuclear cells in the heart of the rat with experimental giant cell myocarditis. Lewis rats were immunized with cardiac myosin in Freund's complete adjuvant (FCA). Severe myocarditis characterized by congestive heart failure and multinucleated giant cells were elicited. The lesions were composed of predominant mononuclear cells, polymorphonuclear neutrophils and fragments of degenerated myocardial fibres. The subsets of infiltrating mononuclear cells were investigated using MoAbs against rat CD4+ T cell (W3/25), CD8+ T cell (CX8), B cell (OX33) and macrophage (OX42). By serial examination, bound immunoglobulin could only be found on degenerated myocardial fibres. In this model, most infiltrating mononuclear cells were composed of macrophages and CD4+ T cells. The frequencies of macrophages and CD4+ T cells were 73.7% and 13.8%, respectively. CD8+ T cells were scarce and B cells were rare in the lesions. The frequencies of CD8+ T cells and B cells were 4.5% and 0.4%, respectively. The dominance of macrophages and CD4+ T cells was the constant finding among the sites of the lesions and throughout the course of the disease. These characteristic subsets of infiltrating cells were in contrast to those of murine viral myocarditis which were mainly composed of natural killer (NK) cells and CD8+ T cells. Clarifying the subsets of infiltrating cells in myocarditis may contribute to differential diagnosis of myocarditis between viral and autoimmune types. From this study, the pathogenesis of experimental autoimmune giant cell myocarditis seemed to be closely related to CD4+ T cells and macrophages.

Animals↗

Efficacy of nafamostat mesilate as a regional anticoagulant in experimental direct hemoperfusion and in plasma exchange on humans.

As an anticoagulant, we compared Nafamostat mesilate (FUT) to heparin in experimental direct hemoperfusion (DHP) and studied the efficacy of FUT in clinical plasma exchange (PE). In in vitro study, FUT (5 micrograms/ml) inhibited the activation of C4 more strongly than heparin (100 U/h), and larger dose of FUT (50 micrograms/ml) inhibited the activation of C3. Experimental DHP with FUT on jaundiced dogs was safely performed, but not with heparin. Clinical PE with FUT was safely performed and the hemostatic condition was not aggravated either during or after PE in patients with bleeding.

Animals↗

On-line cell manipulation for cancer treatment.

We hypothesized that the host immune system is directly stimulated by contact between blood and the materials used in blood purification systems. This concept has never been applied in therapeutic plasmapheresis. Two new materials have been invented since 1983. One of those is lipopolysaccharide (LPS)-immobilized beads, which are chemically bonded bacterial LPS (LPS-B). Another is immobilized pokeweed mitogen (PWM-B). We studied these two materials for their anti-tumor cell activity in vitro and in vivo. Their efficacy on tumor cells was demonstrated to be much stronger than that of lymphocyte activated killer (LAK) cells. Our new concept was proven to be correct.

Animals↗

SPECT findings in Parkinson's disease associated with dementia.

Dementia in Parkinson's disease is thought to be attributable not only to subcortical lesions but also to cortical alterations, especially frontal lobe dysfunction. To evaluate cortical function, the regional cerebral blood flow (rCBF) was estimated of 13 demented and 13 non-demented age matched patients with Parkinson's disease compared with that of 10 age matched controls using I-123 iodoamphetamine single photon emission tomography (IMP-SPECT). The rCBF of the nondemented Parkinson's patients showed no significant differences from that of the control subjects. In the demented patients, the bilateral frontal and parietal and left temporal regional blood flow was significantly less than in the controls. Four demented patients showed isolated frontal hypoperfusion, 8 showed fronto-parietal hypoperfusion, and 1 showed isolated parietal hypoperfusion. Frontal hypoperfusion was therefore present in 12 of the 13 demented patients, and this finding agrees with the frontal lobe dysfunction hypothesis. Parietal rCBF had a significant positive correlation with cortical functions such as calculation and language ability in the MMSE scores. The parietal and temporal reduction in rCBF probably reflects the presence of Alzheimer pathology, cortical Lewy body disease, or both.

Aged↗

Influence of morphologic factors on calcium-containing stone formation.

Pathogenesis of urolithiasis cannot be explained only by metabolic disorder. In the present study, morphologic differences of the renal pelvic-caliceal system (PCS) were examined on both the stone and normal sides in calcium-containing stone formers. The results indicated that as compared to the normal side, the urine flow in the PCS was stagnant or not straight on the stone side even in the same individual, showing unfavorable conditions for stone formation. It is therefore considered that morphologic disorders of the urinary tract may be one of the causes for stone formation.

Adult↗

In vivo lymphocyte-mediated myocardial injuries demonstrated by adoptive transfer of experimental autoimmune myocarditis.

BACKGROUND: To elucidate the mechanisms of immune-related myocardial injuries, we examined whether autoimmune myocarditis was passively transferable by use of humoral or cellular factors. METHODS AND RESULTS: Active myocarditis was elicited in Lewis rats by immunization with human cardiac myosin fraction in complete Freund's adjuvant. This experimental myocarditis was characterized by macroscopic features such as pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac surface. Histologically, extensive myocardial necrosis and numerous inflammatory cell infiltrations were observed. Interestingly, multinucleated giant cells were frequently observed in the lesions. Transfer of the disease by the humoral factor was examined by use of fresh sera and immunoglobulin fraction of pooled sera from rats with severe myocarditis, and transfer by the cellular factor was tested by use of spleen cells and lymph node cells from the diseased rats. When naive Lewis rats were given 15.75 mg of immunoglobulin fraction, no particular change was observed in the hearts. Fresh sera also could not elicit myocarditis in recipient rats. In contrast, intravenous injection of spleen cells or lymph node cells that were cultured for 3 days in the presence of 1 microgram/ml of concanavalin A elicited severe myocarditis. The macroscopic and microscopic findings of passively transferred myocarditis are essentially the same as those found in actively induced myocarditis. Multinucleated giant cells were also observed in the lesions of transferred myocarditis. CONCLUSIONS: This study demonstrates direct evidence for in vivo lymphocyte-mediated myocardial injuries.

Animals↗

Structures of americanol A and isoamericanol A having a neurotrophic property from the seeds of Phytolacca americana.

The structures of new neo-lignans, isoamericanol A (1) and americanol A (2) isolated from the seeds of Phytolacca americana have been elucidated on the basis of spectroscopic data and then confirmed by chemical correlation with the previously known isoamericanin A (3) and americanin A (4). Isoamericanol A, americanol A, and americanin A have been found to enhance choline acetyltransferase activity at 10(-5) M in a cultured neuronal cell system derived from fetal rat hemisphere.

Animals↗

A child with pituitary gigantism and precocious adrenarche: does GH and/or PRL advance the onset of adrenarche?

We describe a female child with pituitary gigantism and precocious adrenarche. From two years of age she showed unusual overgrowth, and at 5 years old she was 133.5 cm (+ 5.5 SD) tall and weighed 40.5 kg. Her precocious manifestations were public hair, acne vulgaris, hirsutism, and advanced bone age. Endocrinological examination revealed markedly increased serum growth hormone (GH) and prolactin (PRL), which responded paradoxically to a TRH test. In addition, the concentrations of serum dehydroepiandrosterone (DHA) and its sulfate (DHAS) were increased to adult levels, moving in accordance with changes in ACTH, which suggested that these androgens were secreted from the adrenal glands functionally. These androgens seemed to be responsible for her partial precocity. Prior reports have suggested that GH and/or PRL overproduction might have played a role in the induction of adrenarche. Also, in previous reports of 9 gigantism patients under 10 years old, the manifestation of precocious adrenarche was suggested in 8. Further investigation of the influence of GH and PRL on adrenal androgen production in children with pituitary gigantism is required. On the other hand, in short children with normal GH secretion, attention should be paid to whether or not the GH therapy in early childhood induces precocious adrenarche.

Adenoma↗

Endocrinological evaluation of GH deficient patient with acromegaloidism showing excessive growth.

In this report we describe the first case of a girl with acromegaloidism in Japan. She had large and coarse facial features with acral enlargement accompanying height overgrowth; these resemble the manifestations of acromegaly and gigantism due to growth hormone (GH) overproduction. However, pituitary function studies revealed a dysfunction of her GH secretion. Moreover, markedly decreased serum somatomedin C (SM-C) levels also indicated impairment of GH secretion. Therefore, GH and SM-C cannot have been responsible for promoting somatic growth. However, serum alkaline-phosphatase (Al-P) and osteocalcin, were increased, indicating that stimulation of bone metabolism was increased without GH and SM-C effects. The patient is a typical case showing growth without GH, and these data suggest the existence of an unidentified growth promoting factor that is independent of GH and SM-C.

Acromegaly↗

Acute hemodynamics of pimobendan in chronic heart failure. A comparative crossover study of captopril and pimobendan.

Acute hemodynamics of pimobendan were compared to captopril in a crossover trial in patients with chronic heart failure (NYHA II-III). Heart failure had been stabilized by conventional therapy with diuretics and digitalis for more than 2 weeks. Patients receiving vasodilators were excluded. The hemodynamics were analyzed using a Swan-Ganz catheter at the bedside during drug administration. Following an intravenous injection of 2.5 mg of pimobendan, there was a significant increase in heart rate and decrease in mean pulmonary artery pressure, total pulmonary resistance, mean arterial pressure, systemic vascular resistance and mean right atrial pressure 2 hours after the injection. Captopril (12.5 mg, orally) significantly decreased mean arterial pressure, systemic vascular resistance and double product 2 hours after administration. In this study, the inotropic effect was evaluated through the relation between the stroke volume index and diastolic pulmonary artery pressure, and also between the stroke volume index and mean arterial pressure. Although decreases of diastolic pulmonary artery pressure and mean arterial pressure were seen with both drugs, the differences in stroke volume index were not significant. In comparison with captopril, the acute hemodynamics of pimobendan are characterized as follows: 1) the systemic arteriovasodilating effects of the two drugs were equal, 2) the pulmonary arteriovasodilating effect of pimobendan was marked, 3) a venodilating effect, documented through a decrease of mean right atrial pressure, was seen only with pimobendan. This study concluded that pimobendan is a stronger arterio-venodilator than captopril.

Aged↗

Tumor necrosis factor-beta and hypercalcemia.

Hypercalcemia in hematological malignancy is frequently encountered in lymphoid malignancies such as adult T-cell leukemia (ATL) and multiple myeloma and is difficult to manage. As a causative agent of hypercalcemia in ATL, tumor necrosis factor-beta (TNF-beta), previously known as lymphotoxin, has been carefully studied and reviewed here. Bone resorption studies showed the presence of activity in culture supernatants of HTLV-I infected cells. Enzyme linked immunosorbent assays (ELISA) for TNF-beta detected elevated TNF-beta in the sera of ATL patients with hypercalcemia. Immunostaining by monoclonal anti-TNF-beta antibody demonstrated the presence of TNF-beta in both HTLV-I infected cell lines and freshly isolated ATL cells. Furthermore biological TNF-beta activity assay including inhibition of anti-TNF-beta antibody confirmed the conventional documentation of TNF-beta activity in the sera and culture supernatants of HTLV-I infected cell lines. These studies showed that the TNF-beta secreted from ATL cells might be one of the factors contributing to the hypercalcemia in patients with ATL functioning as an osteoclast activating factor (OAF).

Animals↗

Endotoxin removed from hemoglobin solution using polymyxin-B immobilized fibre (PMX-F) followed by a new turbidometric endotoxin assay.

Endotoxin contamination in modified hemoglobin can result in side effects. Accurate measurement and effective elimination of endotoxin are important in producing safe hemoglobin preparation. A new turbidometric endotoxin assay (Toxinometer) was studied, in which absorbance of wavelength was applied at 660 nm. This method is not affected by the presence of hemoglobin in solution. This way, toxinometer can accurately measure endotoxin concentration in hemoglobin solution. For the elimination of endotoxin, polymyxin-B immobilized fiber (PMX-F) was studied in-vitro and compared with commercial materials. The PMX-F was found to be a convenient and less expensive approach.

Animals↗