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Biomedical subjects

K Kodama

Publications and source records attributed to K Kodama.

At least 55 records · Page 3Linked to original sources

Medical and socioenvironmental predictors of hospital readmission in patients with congestive heart failure.

BACKGROUND: Patients with chronic congestive heart failure (CHF) require frequent rehospitalization because of the exacerbation of CHF. It is of clinical importance to determine predicting factors for readmission to reduce this likelihood. Previous studies have focused primarily on the demographic and medical characteristics in selected subsets of patients. Therefore, within a broad cohort of consecutively hospitalized patients, we sought to identify not only demographic and medical predictors but also socioenvironmental factors associated with readmission. METHODS: We assessed demographic (age, sex), medical (etiology of CHF, New York Heart Association functional class, left ventricular ejection fraction, previous admission for CHF, length of hospital stay, comorbidity, and medications), and socioenvironmental variables (occupation, financial resources, living alone, and follow-up visits) in 230 patients discharged with a diagnosis of CHF and recorded hospital readmission. RESULTS: Within 1 year after discharge, 81 patients (35%) were readmitted. Five variables, including poor follow-up visits (odds ratio [OR] 4.9, 95% CI 2.0-11.8), previous admission for CHF (OR 3.3, 95% CI 1.8-6.1), no occupation (OR 2.6, 95% CI 1.2-5.5), longer hospital stay (OR 3.2, 95% CI 1.2-8.5), and hypertension (OR 2.0, 95% CI 1.1-3.7), were identified as significant independent predictors for readmission by multivariate logistic regression analysis. CONCLUSIONS: Our independent predictors of readmission support the importance of medical and socioenvironmental factors in the deterioration of CHF. Therefore interventions to decrease readmission should also target social management in all hospitalized patients.

Acute Disease↗

Examination of in vitro chemosensitivity test using collagen gel droplet culture method with colorimetric endpoint quantification.

To develop a simpler method of performing the collagen gel droplet-embedded culture drug sensitivity test (CD-DST), we examined the introduction of colorimetric quantitative determination of images for evaluation of anticancer effect against cancer cells alone in the presence of fibroblasts, based on differences in proliferative morphology and stainability with neutral red of cells within collagen gel drops determined using a video-microscope and NIH Image software. In examinations using a human cancer cell line and a fibroblast cell line, a high degree of linearity between number of cancer cells and image-optical density was found within the range of 10(2) - 10( 6) cells / droplet (r (2) = 0.933). Using NIH Image, fibroblast cells could be eliminated at a cut-off value of 128, and an immunocytochemical method demonstrated that the cells eliminated from the image were indeed fibroblasts, and those remaining were cancer cells. CD-DST was carried out with mixtures of cancer cells with fibroblasts at various ratios, and the feasibility of evaluating anticancer activity in cancer cells alone with no effect of fibroblasts at any mixing ratio was confirmed. In addition, for CD-DST of primary cell cultures of human lung cancers collected at the time of surgery, a high correlation between results obtained with the volume supplementation method, a current cell quantification method, and those with the imaging colorimetric quantification method was obtained (r = 0.933). These results indicate that introduction of imaging colorimetric quantification utilizing NIH Image makes CD-DST a quick and simple method that should be highly useful for clinical chemosensitivity testing using primary cell cultures of human cancers.

Antineoplastic Agents↗

Treatable subsets in cancer of unknown primary origin.

The purpose of this study was to investigate the treatable subsets in cancer of unknown primary origin (CUP). Fifty patients (27 males and 23 females; median age, 53 years) with CUP diagnosed between April 1992 and June 1999 were analyzed retrospectively. Of the 50 patients, 39 received chemotherapy: platinum-based in 31, non-platinum-based in 4, and clinical trials of new agents in 4. Of the 39 patients, 13 (33.3%; 95% confidence interval: 19.1 - 50.2%) showed objective responses, with 4 complete responders. Patients with poorly differentiated carcinomas in whom beta-subunit of human chorionic gonadotropin (beta-HCG) was elevated more than 10 mIU / ml and female patients with peritoneal adenocarcinomatosis achieved high response rates (83.3% and 80%, respectively) with platinum-based chemotherapy, as compared with only a 15.3% response rate in the remaining patients. Platinum-based chemotherapy provided promising results in patients with poorly differentiated carcinomas and in female patients with peritoneal adenocarcinomatosis. Significantly elevated serum levels of beta-HCG in patients with poorly differentiated carcinoma might predict a better response to platinum-based chemotherapy. However, the investigation of novel chemotherapeutic approaches is warranted for other groups of patients with CUP.

Adenocarcinoma↗

T-cell responses to mitogens in atomic bomb survivors: a decreased capacity to produce interleukin 2 characterizes the T cells of heavily irradiated individuals.

Significant decreases in the fraction of lymphocytes that are CD4(+) and increases in serum levels of some classes of immunoglobulin have been reported to occur in atomic bomb (A-bomb) survivors and in victims of the Chernobyl nuclear plant accident. To investigate the long-term effects of nuclear radiation on cellular immunity in more detail, we used limiting dilution assays with peripheral blood mononuclear cell preparations to analyze the T-cell responses of 251 A-bomb survivors exposed to less than 0.005 Gy and 159 survivors exposed to more than 1.5 Gy. The percentages of CD2-positive cells that were capable of proliferating in response to phytohemagglutinin (PHA) in the presence of exogenous interleukin 2 (IL2) did not differ substantially between distally exposed and more heavily exposed survivors. The heavily exposed survivors appeared to possess fewer T cells that were capable of proliferating in response to concanavalin A (Con A) or of producing interleukin 2. Assuming that CD4 T cells were the ones primarily responsible for producing IL2 in response to Con A, we were able to estimate how many cells in any given CD4 T-cell population were actually producing IL2. The results indicated that peripheral blood samples from heavily exposed survivors contained significantly fewer IL2-producing CD4 T cells than did similar samples from distally exposed survivors, indicating that significant exposure to A-bomb radiation may have a long-lasting negative effect on the capacity of CD4 T-cell populations to produce IL2.

Adult↗

Organ doses from radiation therapy in atomic bomb survivors.

Previous surveys of radiation therapy among the Life Span Study (LSS) population at the Radiation Effects Research Foundation (RERF) revealed that 1,670 (1.4%) of the LSS participants received radiation treatments before 1984. The data on therapeutic radiation doses are indispensable for studying the relationship between radiation treatments and subsequent cancer occurrences. In this study, the radiation treatments were reproduced experimentally to determine the scattered radiation doses. The experiments were conducted using a female human phantom and various radiation sources, including a medium-voltage X-ray machine and a (60)Co gamma-ray source. Doses were measured using thermoluminescence dosimetry and ionization chambers. Radiation doses were determined for the salivary glands, thyroid gland, breast, lung, stomach, colon, ovary and active bone marrow. The results have been used for documenting the organ doses received by patients in previous surveys. The contribution of therapeutic irradiation to the occurrence of chromosome aberrations was studied using data on doses to active bone marrow from both radiation treatments and atomic bomb exposures in 26 RERF Adult Health Study participants. The results suggest that radiation treatments contributed to a large part of their frequencies of stable-type chromosome aberrations. The therapeutic radiation doses determined in the present study are available for investigating the effects of therapeutic irradiation on the subsequent primary cancers among atomic bomb survivors who received radiation treatments.

Chromosome Aberrations↗

Peripheral blood stem cell transplantation in patients over 65 years old with malignant lymphoma--possibility of early completion of chemotherapy and improvement of performance status.

OBJECTIVE: After the initial clinical application of peripheral blood stem cell transplantation (PBSCT) in the latter half of the 1980s, the frequency of PBSCT for non-Hodgkin's lymphoma (NHL) has been gradually increasing. At present, PBSCT is an important procedure for treating young patients with NHL. This procedure is now being increasingly used as a part of the chemotherapy regimen for elderly patients. We evaluated the feasibility of PBSCT in elderly patients with malignant lymphoma. PATIENTS AND METHODS: We performed PBSCT on four older patients over 65 years old (median age 71, range 66-78) with aggressive non-Hodgkin's lymphoma. Patients were initially treated with the THP-COP [cyclophosphamide, THP-doxorubicin (pirarubicin), vincristine, prednisolone] regimen as first-line chemotherapy. As second-line chemotherapy, in partial response (PR) cases, we performed PBSCT. Conditioning therapy was the MCVC [ranimustine (MCNU), carboplatin, etoposide (VP-16), cyclophosphamide] protocol. RESULTS: PBSC collection and transplantation were possible in all patients. We observed no severe toxicity. Two of the four patients attained complete remission (CR). Tumor size was clearly diminished in two PR patients. Performance status (PS) was improved in three of the four patients after transplantation. CONCLUSION: Despite the small number of cases, this procedure is beneficial for completing chemotherapy earlier and promoting a good quality of life.

Age Factors↗

Elevated serum IP-10 levels observed in type 1 diabetes.

OBJECTIVE: Although most patients with type 1 diabetes are considered to have T-cell-mediated autoimmune disease, a method of measuring of pancreatic beta-cell-specific T-cell function in cases of type 1 diabetes has yet to be established. Here, we focused on interferon-inducible protein-10 (IP-10), a chemokine that promotes the migration of activated T-helper 1 (Th1) cells and measured serum IP-10 levels in patients with human type 1 diabetes, which is regarded as a Th1-mediated disease. RESEARCH DESIGN AND METHODS: Serum samples were obtained from diabetic patients, and the levels of autoantibodies (GAD and insulinoma-associated protein-2 [IA-2]) and IP-10 were measured. Diabetic patients positive for either or both of the autoantibodies were classified as Ab+ type 1, and those negative for both were classified as Ab type 1. To evaluate islet antigen-specific responses, peripheral blood from patients stimulated with or without GAD was used, and intracellular cytokine staining for flowcytometry was performed. RESULTS: The Ab+ and Ab- type 1 groups both showed a significantly higher serum IP-10 level than the healthy subjects (P < 0.001 and P < 0.05, respectively), and the IP-10 level in the recent-onset Ab+ subgroup was significantly higher than that in the established (longstanding) Ab+ subgroup (P < 0.002). Furthermore, there was a significant positive correlation between the serum IP-10 level and the number of GAD-reactive gamma-interferon-producing CD4+ cells in the Ab+ type 1 group (P < 0.007). CONCLUSIONS: Our findings demonstrate that measurement of serum IP-10 concentrations is useful in patients with type 1 diabetes.

Adult↗

[Binge-eating in simple obesity].

Binge eating in simple obesity has recently been recognized as a serious clinical problem. In the obese population with binge eating, distinct characteristics have been found by many researchers, such as an early onset of obesity and diet, frequent body weight fluctuation, the amount of time spent dieting, extreme restriction of food intake and an unrealistic ideal of diet. Obese binge eaters also exhibit more psychiatric symptomatology such as distortion of body image, low self-esteem, low self-efficacy, a high level of depression, strong perfectionism, high impulsivity and comorbidity of personality disorders, especially a borderline personality disorder. Cognitive-behavioral therapy and interpersonal psychotherapy are promising for treatment of obese binge eaters. Supportive psychotherapy will add some help by ameliorating psychological distress.

Adult↗

Expression of neural plasticity related gene in the pontine tegmental area of rats with overactive bladder after cerebral infarction.

PURPOSE: We investigated the expression of the neural plasticity related genes c-fos, zif268, c-jun, brain-derived neurotrophic factor and tissue plasminogen activator in the pontine tegmental area in rats with overactive bladder induced by cerebral infarction. MATERIALS AND METHODS: Cerebral infarction was induced by left middle cerebral artery occlusion in female Sprague-Dawley rats. Bladder activity was monitored by continuous infusion cystometrography in awake rats. Specimens were obtained from the pontine tegmental area 1, 3, 5, 12 and 24 hours after cerebral infarction or sham operation. The effect of 0.1 mg./kg. intravenously of the N-methyl-d-aspartate glutamatergic receptor antagonist MK-801 on bladder activity, and c-fos and zif268 expression after middle cerebral artery occlusion were studied. Real-time reverse transcriptase-polymerase chain reaction was performed with the LightCycler system (Roche Diagnostics, Mannheim, Germany) to evaluate cerebral infarction influences on gene expression in the pontine tegmental area. RESULTS: Bladder capacity in cerebral infarcted rats was significantly reduced 1 to 24 hours after middle cerebral artery occlusion compared with that of sham operated rats (p <0.05 to 0.01). One hour after occlusion mean c-fos messenger (m)RNA expression plus or minus standard error had significantly increased to 18.9 +/- 4.0 in terms of its density relative to the outer control in a sample obtained immediately after occlusion compared with that in sham operated rats (p <0.05). It returned to the control level within 3 hours after occlusion. Mean zif268 mRNA expression significantly increased to a relative density of 3.2 +/- 1.4 3 hours after middle cerebral artery occlusion (p <0.01) and returned to the control level within 5 hours after occlusion. The expressions of c-jun, brain-derived neurotrophic factor and tissue plasminogen activator was not influenced by occlusion. Pretreatment with MK-801 inhibited bladder overactivity and significantly reduced the expression of c-fos and zif268 mRNA in the pontine tegmental area. CONCLUSIONS: These results indicate that the development of bladder overactivity after middle cerebral artery occlusion is mediated by activation of an N-methyl-d-aspartate receptor and accompanied by an increase in c-fos and zif268 mRNA expression in the pontine tegmental area.

Animals↗

4-(3-Chloro-4-methoxybenzyl)aminophthalazines: synthesis and inhibitory activity toward phosphodiesterase 5.

We synthesized various 4-(3-chloro-4-methoxybenzyl)aminophthalazines substituted at the 1- and 6-positions and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) and their vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F2alpha (10(-5) M). The preferred substituents at the 1-position of the phthalazine were 4-hydroxypiperidino, 4-hydroxymethylpiperidino, 4-(2-hydroxyethyl)piperidino, and 4-oxopiperidino. Among these compounds, [4-(3-chloro-4-methoxybenzyl)amino-1-(4-hydroxy)piperidino]-6-phthala zinecarbonitrile monohydrochloride (13) exhibited potent PDE5 inhibitory activity (IC(50) = 0.56 nM) with >1700-fold high selectivity over other PDE isozymes (PDE1-4). Compound 13 exhibited the most potent vasorelaxant action (EC(50) = 13 nM) in this series of compounds. Compound 13 reduced mean pulmonary arterial pressure by 29.9 +/- 3.1% when administered intravenously at 30 microg/kg to the chronically hypoxic rats and had an apparent oral bioavailability of about 19.5% in rats and was selected for further biological evaluation.

3',5'-Cyclic-GMP Phosphodiesterases↗

Direct evidence for the localized single-triplet excitations and the dispersive multitriplet excitations in SrCu2(BO3)2.

We performed inelastic neutron scattering on the 2D Shastry-Sutherland system SrCu2(11BO3)2 with an exact dimer ground state. Three energy levels at around 3, 5, and 9 meV were observed at 1.7 K. The lowest excitation at 3.0 meV is almost dispersionless with a bandwidth of 0.2 meV at most, showing a significant constraint on a single-triplet hopping owing to the orthogonality of the neighboring dimers. In contrast, the correlated two-triplet excitations at 5 meV exhibit a more dispersive behavior.

Journal Article↗

Vasorelaxant effect of a phosphodiesterase 3 inhibitor, olprinone, on isolated human radial artery.

The radial artery is currently used as a viable arterial conduit for myocardial revascularization. The aims of this study were to identify phosphodiesterase 3 isoenzyme in the human radial artery isolated for coronary artery bypass grafting, and to examine the vasorelaxant effect of a cardiotonic and vasodilating phosphodiesterase 3 inhibitor, 1, 2-dihydro-6-methyl-2-oxo-5-(imidazo[1,2-a]pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate (olprinone). The phosphodiesterase 3 isoenzyme was separated from the radial artery by DEAE-Sepharose chromatography. Olprinone inhibited the phosphodiesterase 3 activity with an IC(50) value of 1.25 microM. Olprinone relaxed the phenylephrine-induced contractions of endothelium-denuded arterial strips with an EC(50) value of 0. 107+/-0.029 microM (n=5). These findings indicate that the human radial artery possesses phosphodiesterase 3 isoenzyme activity and olprinone causes potent relaxation of the arterial strip in vitro through inhibition of phosphodiesterase 3 isozyme activity.

Endothelium, Vascular↗

Familial frontotemporal dementia with a P301L tau mutation in Japan.

We have reported the family line with frontotemporal dementia (FTD) in Japan. This family line has so far included four patients. Patient II-1 (man) had a 10 year history of slowly progressive personality and behavioral changes and died at the age of 56. His neuropathological examination showed severe atrophy of the bilateral frontal and temporal cortices with neuronal loss, gliosis and superficial spongiosis. Pick bodies were not found. The neuropathological diagnosis was atypical Pick's disease without Pick bodies or Pick-type in FTD. Patient III-2 is patient II-1's oldest daughter and was taken ill with personality change at the age of 52. She died at the age of 68. Patient III-4 is patient II-1's second daughter. Her onset with strange speech and behavior was at the age of 59. Patient III-5 is patient II-1's oldest son. He also had onset with personality change at the age of 54 and had the P301L mutation in tau. In all III generation cases CT/MRI revealed circumscribed frontotemporal atrophy. Patient III-5's PET/SPECT showed signs of hypoperfusion or hypometabolism in the bilateral frontotemporal areas. This is the first report of familial FTD with the P301L mutation in Japan.

DNA Mutational Analysis↗