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Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

At least 163 records · Page 9Linked to original sources
PubMed1998

Extracorporeal endotoxin removal by polymyxin B immobilized fiber cartridge: designing and antiendotoxin efficacy in the clinical application.

We have developed an extracorporeal hemoadsorption cartridge, the PMX cartridge, to eliminate endotoxin from peripheral blood circulation. As an adsorbent, a polymyxin B covalently immobilized fiber (PMX-F) was developed. After the optimization of the condition of immobilization, fixed polymyxin B maintained its ability to adsorb endotoxin and its bactericidal activity. PMX-F could detoxify many kinds of endotoxin in vitro. Fixed polymyxin B was estimated to interact with the lipid A portion of endotoxin. Utilization of fibrous adsorbents enabled us to design the PMX cartridge with a large surface area and low blood pressure drop in the blood flow compartment and to apply it safely to the direct hemoperfusion procedure. In Japan, the PMX cartridge is now being clinically applied as one of the therapeutical interventions for sepsis, septic shock, and septic multiple organ failure. In multicenter clinical studies, the blood endotoxin level has been significantly decreased. Accompanied with elimination of endotoxin, hemodynamic abnormalities such as low blood pressure and low systemic vascular resistance were significantly improved. In more recent multicenter studies, the average number of failed organs; severity of illness score, such as Goris score; and vasopressor dosage were significantly decreased. The PMX cartridge is expected to be effective in the intervention for the treatment of septic shock. Endotoxin may be one of the therapeutical targets for the treatment of sepsis.

Adolescent↗
PubMed1998

Blood purification therapy in cancer treatment.

It is well known that cancer patients have specific and nonspecific immunosuppressive substances in their sera that depress cellular immunity. Plasma exchanges have been attempted to remove these immunosuppressive factors and improve the immunity to cancer. Double infiltration plasmapheresis has also been attempted and has been found to remove the immunosuppressive substances efficiently without a large volume substitution. Using these methods, an improvement in performance status and clinical symptoms and reduction of tumor size have been observed. Cancer chemotherapy has several severe side effects. Double filtration plasmapheresis is also clinically applied as a surplus carcinostatic drug adsorption method to alleviate systemic adverse reactions.

Adsorption↗
PubMed1998

S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1.

S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two-to three-drug combination therapy for HIV infection.

Animals↗
PubMed1998

Recovery from complete atrioventricular block caused by idiopathic giant cell myocarditis after corticosteroid therapy.

Giant cell myocarditis (GCM) is a rapidly progressive disease that leads to ventricular tachycardia or high-grade atrioventricular (A-V) block, frequently requiring a pacemaker. A 64-year-old woman developed syncope as a result of idiopathic GCM with A-V block. She required both a temporary and a permanent pacemaker. Two-dimensional echocardiography showed severely reduced wall motion. There was no histologic or clinical evidence to suggest sarcoidosis. Despite treatment with diuretics and an angiotensin-converting enzyme inhibitor, exertional dyspnea persisted. She received prednisolone 4 months after the onset of complete A-V block in the late phase of GCM. Prednisolone improved A-V nodal conduction in spite of the fact that there was no influence from LV wall motion, and sinus rhythm has continued for more than 2 years. In this patient, prednisolone was effective in the treatment of GCM.

Anti-Inflammatory Agents↗
PubMed1998

Hypertrophic cardiomyopathy with type I CD36 deficiency.

CD36 is a multifunctional membrane-type receptor glycoprotein that reacts with oxidized low-density lipoprotein and long-chain fatty acid (LCFA). A patient presented with hereditary hypertrophic cardiomyopathy (HCM) and type I CD36 deficiency (neither platelets nor monocytes expressed CD36) but showed no myocardial LCFA accumulation. CD36 was expressed in the capillary endothelial cells of the cardiac muscle of a control subject, while the patient's myocardial capillary endothelial cells were completely CD36-negative. These results suggest that type I CD36 deficiency is closely related to hereditary HCM and lack of myocardial LCFA accumulation.

CD36 Antigens↗
PubMed1998

A new scoring system to predict the efficacy of steroid therapy for patients with active myocarditis--a retrospective study.

The efficacy of steroid therapy for active myocarditis is controversial, so a new scoring system was constructed based on 6 clinical parameters: (1) the mode of onset of the disease; (2) complications of immune-related systemic disorders; (3) evidence of viral infection; (4) the population of infiltrating inflammatory cells; (5) the appearance of multinucleated giant cells in endomyocardial biopsy specimens; and (6) the duration of active myocarditis. Points from -2 to +2 were assigned to each parameter and the total score was calculated from the 6 parameters. Twenty-one patients with clinically suspected myocarditis, who had been admitted to hospital from 1987, were retrospectively analyzed by this scoring system. Sixteen patients were treated without corticosteroids at presentation, and 5 patients were treated by conventional methods with adjunctive use of corticosteroids. In 10 patients of the non-steroid group myocarditis improved and their mean score was -4.8 at presentation. In 6 patients of the non-steroid group, myocarditis and cardiac symptoms persisted after initial therapy, and their score at presentation was -0.8. In 2 patients of the steroid group myocarditis improved after initial therapy and their score was +2. In 2 other patients of the steroid group, myocarditis and cardiac symptoms persisted and their score was +3. Another patient of the steroid group died from congestive heart failure and his score was -5 at presentation. In 8 of 9 patients with persistent myocarditis, the secondary phase therapy was challenged. Seven patients were treated with corticosteroids and 6 patients improved. Their score at the secondary phase was +2.5. Overall, non-steroid conventional treatment was successful in patients with the scores from -5 to -4, and steroid therapy succeeded in patients with scores from 0 to +6. Although this is a retrospective study, this scoring system is able to predict the efficacy of steroid therapy in patients with clinically suspected active myocarditis.

Acute Disease↗
PubMed1998

Comparative epidemiology of cancers of the testis, lung, bladder and stomach with special reference to the possible implication of environmental hormones in the recent risk changes of the 4 neoplasia types.

The purpose of this study is to extract common features of an environmental hormone-oriented neoplasia by comparatively investigating the epidemiological characteristics of testicular cancer in Denmark with those of other cancers, of which the age-adjusted incidence rates (AAIRs) underwent remarkable increase or decrease in the time range of early 1960's to mid 1980's. Practically, the log-transformed (log) AAIRs and the corresponding log ASIRs (age-specific incidence rates) were used in parallel to investigate the dynamic aspect of cancer risk changes in time and space. The present study includes cancers of the testis, lung, bladder and stomach as study subjects, and followed the chronological transition of cancer risk for each tumor type and for each population unit from early 1960's to mid 1980's. In space, the present study includes the data for 6 population units as follows: Denmark, Birmingham-England, the State of New York less New York city, Miyagi-Japan, Puerto Rico and Cali-Colombia. Since 3 neoplasias other than testicular cancer were associated with male predominance of cancer risk, 1st order regression analysis was applied to a set of 5 chronologically consecutive data of log AAIRs for a given tumor to comparatively investigate the sex discrimination of cancer risk for each of 3 neoplasia types. Results obtained are as follows: a) the ASIR profile of testicular cancer in Denmark (a high-risk country) was a composite of an adult type surge and an infant type surge (a product of in utero carcinogenic insult). Consistent ascension of both the adult type surge and the infant type surge of the ASIR profile was observed in parallel with the straight line increase of log AAIR of testicular cancer in Denmark. b) The ASIR profiles of testicular cancer for Miyagi-Japan (a low-risk country with steady increase of log AAIR) experienced new emergence of the infant type surge that was detectable in the profile for the years 1968-1971 and 1983-1987, but not in the profile for the years 1959-1960. c) The ASIR profiles of testicular cancer for Cali-Colombia (a low-risk country with no sign of risk increase) was free of the infant type surge throughout the study period. d) Temporary emergence of the infant type surge was experienced in cancers of the lung and bladder in early 1970's. In space, the infant type surge had preference of occurrence for a high-risk country to a low-risk country, and for a male population to a female population. e) Another feature of environmental hormone-oriented tumor was found in the recent risk decrease of gastric cancer of which the rate of risk decrease was distinct in Western countries and Japan, but not in Cali-Colombia. Puerto Rico was ranked as an in-between existence--a violation to the rules of Westernization effect for cancer risk. f) The relation between the male log AAIR and the male log AAIR less female log AAIR for a given tumor type was found to have a good fitness to the equilibrium model of which the members are destined to interact with each other under the law of mass action. The above mathematical strictness was found to be valid with all of cancers of the liver, skin, lung, bladder, stomach and esophagus--a finding to indicate that the relation between the changes of male cancer risk and that of female cancer risk in time and space is defined by the law of mass action regardless of the presence or absence of environmental hormone impact, and that no marker is available to detect possible implication of the environmental hormones with this system. g) The significance of the last finding in cancer etiology was discussed in the light of the steroid criminal hypothesis of human carcinogenesis in general. In conclusion, the recent risk changes of cancers of all the testis, lung, bladder and stomach in high-risk areas are in part to be explained in terms of the environmental hormone impact.

Denmark↗
PubMed1998

Treatment of superficial cancer of the esophagus: a summary of responses to a questionnaire on superficial cancer of the esophagus in Japan.

BACKGROUND: Histopathologic characteristics and optimal treatment modality for superficial esophageal cancer were reevaluated on the basis of 2418 patients from 143 institutions through a nationwide questionnaire to the members of the Japanese Society for Esophageal Diseases. METHODS: A questionnaire was designed for patients with preoperatively untreated superficial cancer of the esophagus who had undergone either surgical or endoscopic treatment between January 1, 1990, and December 30, 1994. Mucosal cancer and submucosal cancer were divided into three subclasses according to the criteria formulated by the Society. RESULTS: The incidence of positive lymphatic invasion or lymph node metastases tended to increase markedly as cancer infiltrates reached the lamina muscularis mucosa. The majority of the cases with 0-I or 0-III components were submucosal cancer. The indication of endoscopic mucosal resection (EMR) was limited to mucosal 1 and mucosal 2 superficial cancer in 76% of the institutions surveyed. Tumors measuring 2 cm or more in diameter were resected piecemeal in 94% of patients. Complications of EMR, including perforation, stenosis, and hemorrhage, were observed in approximately 6.8% of patients. Almost all patients with mucosal 1 or mucosal 2 cancer are still alive. There was no significant difference in prognosis between mucosal 3 cancer and mucosal 1 or mucosal 2 cancer, but submucosal 1 cancer showed worse prognosis than mucosal cancer. CONCLUSIONS: Local resection of cancer lesions is regarded as the treatment of choice against the superficial esophageal cancers limited to the lamina propria mucosae. Further study is advocated to define the treatment strategy against mucosal 3 or submucosal 1 cancer.

Aged↗
PubMed1998

Relationship between area under the concentration versus time curve of cyclosporin A, creatinine clearance, hematocrit value, and other clinical factors in Japanese renal transplant patients.

We evaluated the relationship between the area under the concentration versus time curve (AUC) of cyclosporin A (CsA) and several other clinical factors, because the clinical utility of AUC monitoring has been ambiguous. Fifty-four clinical time courses from 14 Japanese renal transplant patients during hospitalization, in the period from April 1990 to March 1997, were examined. In a bivariate regression analysis there was no correlation between the AUC and the daily dose of CsA (mg/kg/day) when the individual data or total series data were analyzed. In a chi-square test, the donor type of kidney (chi(2) = 25.254, df = 1, p = 0.0000) and renal function-related episodes, i.e. acute tubular necrosis, hemodialysis, hypertension, nephrotoxicity, or rejection (chi(2) = 13.982, df = 1, p = 0.0002) directly affected posttransplant renal function assessed by creatinine clearance, while episodes of hepatic function as assessed by the glutamate-pyruvate transaminase (GPT) activity level had no correlation with the posttransplant renal function evaluated according to creatinine clearance. In contrast, the renal function-related episodes significantly affected the AUC after renal transplantation (chi(2) = 4.934, df = 1, p = 0.0263), while hepatic function assessed by GPT did not. In a multivariate analysis, the creatinine clearance and obesity had significant positive correlations with the AUC, whereas the hematocrit had a significant negative correlation with the AUC. From these observations, we concluded that the dosage adjustment of CsA cannot be performed using the linear relationship between the daily oral dose and the AUC, and that renal function, obesity, and the CsA blood distribution properties affect the CsA pharmacokinetics after renal transplantation. Posttransplant renal function as well as obesity and CsA blood distribution properties are important factors to be considered when therapeutic monitoring is performed.

Adult↗
PubMed1998

[Sepsis and organ failure--its pathogenesis and treatment].

Sepsis, septic shock, and multiple organ dysfunction are heterogeneous and sophisticated clinical syndromes which result from the interplay of mediators of cellular function and inflammation. Secondary mediators such as lipids (prostaglandin, thromboxane, platelet-activating factor), peptides (bradykinin, vasoactive intestinal peptide), amines (histamine, serotonin) and complements are key mediators which lead to the state of shock in human sepsis. Endotoxin may also cause multiple organ dysfunction syndrome (MODS). New antiendotoxin treatment and the strategy for sepsis including endotoxemia are reviewed. Monoclonal antibodies directed at core epitopes and lipid A (E5, HA1-A) could not reproduce the beneficial effects. Bactericidal/permeability increasing protein (BPI)). Endotoxin neutralizing protein (ENP)) and E5531 may have potential in the treatment of sepsis. Another treatment using extracorporeal endotoxin removal is reported. Polymyxin B immobilized fiber (PMX), commercialized as Toraymyxin, is now widely used in Japan for severe sepsis and septic MODS. PMX treatment improves the symptoms related to the septic state, a hemodynamic disorders, and cytokine levels including tumor mecrosis factor, interleukin (IL)-6, and IL-10, with a decrease in endotoxin levels. Phase II, III, and IV clinical trials with extracorporeal endotoxin removal by PMX revealed that endotoxin removal is helpful in the treatment of septic patients.

Humans↗
PubMed1998

Colonial growth and differentiation of epithelial cells derived from abattoir adult porcine livers.

The parenchymal cell fraction was isolated from abattoir adult porcine livers and cultured in Dulbecco's Modified Eagles' medium/Ham's F12 medium (DMEM/F12; 1:1) medium supplemented with 5% foetal calf serum, 10 ng/mL glucagon, 10 microg/mL insulin, 60 ng/mL hydrocortisone and eight other factors (NAIR-1 medium). The fraction contained a number of epithelial cells other than hepatocytes, some of which attached to the culture plates as cell clusters and began to grow after 3 days in culture. These epithelial cells growing as colonies were found to express cytokeratin 18 by immunocytochemistry. After 7-8 days, duct-like structures emerged in the central parts of the colonies. The cells constituting the duct-like structures and some cells located outside the structures were positive for cytokeratin 19 and gamma-glutamyltransferase (GGT). The albumin-positive cells were located in the outer parts of the colonies rather than their central parts. Albumin was also detectable in the cells surrounded by the duct-like structures. Moreover, cytochrome P450 IA1 was induced by 3-methylcholanthrene (3-MC) on day 16. These results suggest that porcine liver epithelial cell clusters may contain stem-like cells which can differentiate into mature hepatocytes or bile duct epithelial cells.

Albumins↗
PubMed1997

The PU.1 binding site is a cis-element that regulates pro-B/pre-B specificity of Vkappa-Jkappa joining.

We have previously shown that the PU.1 binding motif (GAG GAA) in the 3'-enhancer region in the Ig kappa gene is responsible for the negative regulation of tissue (B/T)-specific Vkappa-Jkappa joining. Here we report that the PU.1 binding site also regulates the stage (pro-B/pre-B) specificity of Vkappa-Jkappa joining. In the substrate with base substitutions in the PU.1 binding motif, recombination took place in both pro-B (B220dull/CD43+) and pre-B (B220dull/CD43-) cells. In the transcriptional regulation, the PU.1 motif acts in a positive manner cooperatively with the nuclear factor-EM5 (or PIP) motif (GAAAAC), which is located 2 bp downstream from the PU.1 motif. Interestingly, base substitutions in the nuclear factor EM5 (PIP) motif did not affect the pro-B/pre-B specificity of Vkappa-Jkappa joining. Thus, the PU.1 motif regulates both temporal and tissue-specific rearrangements, while nuclear factor-EM5 is not involved in the regulation of Ig kappa recombination.

Animals↗
PubMed1997

Interlamellar waters in dimyristoylphosphatidylethanolamine-water system as studied by calorimetry and X-ray diffraction.

The number of water molecules incorporated into the interlamellar region in a gel phase of dimyristoylphosphatidylethanolamine (DMPE)-water system containing up to about 40 g% water was estimated by techniques of calorimetry and X-ray diffraction. The calorimetric estimation based upon enthalpy changes of deconvoluted ice-melting peaks revealed that bulk water existing outside lipid bilayers begins to appear although the gel phase is not fully hydrated. The gel phase showed a linear depression of its transition temperature proportional to the amount of freezable waters interposed between bilayers. For a fully hydrated gel phase, the numbers of non-freezable and freezable interlamellar waters estimated by calorimetric analysis were about 2.3 and 3.7 molecules per lipid, respectively. The limiting, total number of interlamellar waters, 6 H2O/lipid, agreed with that estimated from both the X-ray diffraction data and the absolute specific volume for a DMPE molecule. Furthermore, the analysis for the lamellar intensity data is also consistent with the result of calorimetric analysis.

Calorimetry, Differential Scanning↗
PubMed1997

Alterations of calmodulin and its mRNA in rat brain after acute and chronic administration of methamphetamine.

The effect of acute and chronic administration of methamphetamine (METH) on the levels of calmodulin (CaM) and its mRNAs has been investigated in rat brain using antisense oligonucleotides to three distinct rat CaM genes (CaM I, CaM II, CaM III). CaM I mRNA was reduced in the striatum and nucleus accumbens within 2 h of acute administration of 4 mg/kg METH, but returned to the control level by 6 h. The CaM content in both the cytosolic and membrane fractions of the striatum was reduced 0.5, 2, and 6 h after acute administration of METH. In the chronic experiments, rats were treated with either 4 mg/kg METH or saline once daily for 14 days. This was followed by a withdrawal period of 28 days, and thereafter, the animals were challenged with either METH (4 mg/kg, i.p.) or saline. All the animals were decapitated 6 h after this injection. There were four treatment groups: METH-METH (MM); METH-saline (MS); saline-METH (SM); and saline-saline (SS). There was a significant decrease in the mRNA for CaM I and CaM II in the striatum, and CaM II and CaM III in the nucleus accumbens in the MS group and the MS and MM groups, respectively, when compared to the SS group. The CaM content in the striatal membrane fraction decreased in both the SM and MS groups but not in the MM group. In contrast, the CaM content in the membrane fraction of the mesolimbic area showed a significant increase in the MM group. The CaM content in the cytosolic fraction of these brain areas decreased in both the SM and MM groups. The total CaM decreased significantly in the SM and MM groups of the striatum, but increased significantly in the MM group of the mesolimbic area. The mRNA for CaM I and CaM III decreased significantly in the MM group, and in the SM and MM groups, in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA), respectively. The CaM content in both the cytosolic and membrane fractions and total CaM content of the SN/VTA decreased significantly in the SM, MS and MM group as compared with the SS group. In the medial prefrontal cortex and hippocampus the significant increase of CaM content in the membrane fraction of the MM group was also found, but neither the CaM content in the cytosol fraction nor total CaM content changed. These results suggest that chronic METH administration leads to a translocation of CaM from the cytosolic to membrane fractions; these may underlie METH-induced behavioral sensitization.

Animals↗
PubMed1997

Cellular localization of urokinase-type plasminogen activator, its inhibitors, and their mRNAs in breast cancer tissues.

The plasminogen activation (PA) system may participate in cancer invasion and metastasis. A series of breast cancer tissue specimens was analysed using in situ hybridization and immunohistochemistry. Urokinase-type plasminogen activator (u-PA) mRNA was detected in cancer cells and fibroblasts adjacent to them and its expression was found to be more intense in invasive than in intraductal regions. In invasive but not in intraductal regions, especially those with abundant stroma, plasminogen activator inhibitor-1 (PAI-1) mRNA was observed in cancer cells, fibroblasts, macrophages, and endothelial cells, and PAI-2 mRNA was present in cancer cells, and fibroblasts, macrophages, and lymphocytes around them. These PAI-1- and PAI-2-positive cancer cells were localized at the periphery of the invasive front. Immunohistochemistry yielded basically similar results. A retrospective study of surgically resected breast cancers from 73 patients revealed significant clinical differences associated with u-PA and PAI-2 expression in cancer cells, associated with a poor and a good prognosis, respectively. These findings indicate that breast cancer cells and fibroblasts express u-PA initially and then its inhibitors, and that this process is related to invasion. Expression of u-PA and PAI-2 in cancer cells themselves may serve to up-regulate and limit PA-mediated invasion and metastasis, respectively.

Adult↗