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Biomedical subjects

T Kodama

Publications and source records attributed to T Kodama.

At least 37 records · Page 2Linked to original sources
PubMed2004

Fluctuations of the initial conditions and the continuous emission in the hydrodynamical description of two-pion interferometry.

Within the hydrodynamical approach, we study the Bose-Einstein correlation of identical pions by taking into account both event-by-event fluctuating initial conditions and continuous pion emission during the whole development of the hot and dense matter formed in high-energy collisions. Important deviations occur, compared to the usual hydrocalculations with smooth initial conditions and a sudden freeze-out on a well defined hypersurface. Comparison with data at the BNL Relativistic Heavy Ion Collider (RHIC) shows that, despite the rather rough approximation we used here, this description can account for the m(T) dependence of R(L) and R(s), and produces a significant improvement for R(o) with respect to the usual version.

Journal Article↗
PubMed2004

Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer.

Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.

Adult↗
PubMed2004

A nonsense mutation (R220X) in the alpha-galactosidase A gene causes typical Fabry disease in both genders.

BACKGROUND: Fabry disease is an X-linked recessive disorder resulting from a deficiency of lysosomal alpha-galactosidase A (alpha-Gal A). Chronic renal failure is an important cause of death in patients with Fabry disease. We report on patients with Fabry disease (a hemizygous male and his mother) due to a nonsense mutation (R220X) in the alpha-Gal A gene. METHODS: The proband, a 41-year-old man, and his 71-year-old mother presented with renal and cardiac manifestations of Fabry disease. Histological examination and molecular analysis of the alpha-Gal A gene were performed. RESULTS: Typical histological findings of Fabry disease were observed in a renal biopsy specimen from the proband and in renal and myocardial necropsy specimens from the mother. Sequencing of a full-length alpha-Gal A cDNA from the proband indicated a C-T transition at codon 220, resulting in substitution of the predictable termination for arginine (R220X). Examination of genomic alpha-Gal A DNA revealed that the proband was a hemizygote and the mother was a heterozygous carrier for the mutation. CONCLUSION: This is the first detailed report of family members with Fabry disease due to a nonsense mutation (R220X) in the alpha-Gal A gene. Our study indicates that this mutation causes the typical disease in both genders.

Adult↗
PubMed2004

[Lung metastasis with a 12 years disease free interval from the first surgery of synovial sarcoma; report of a case].

A 48-year-old woman was admitted for surgery on a lung tumor found incidentally. Her medical history showed a synovial sarcoma of left inguinal region which was resected 12 years ago. We performed segmentectomy of left S4 + 5 to removed the metastatic tumor. Histological examination revealed that the tumor was metastatic synovial sarcoma. Synovial sarcoma can metastasize to lung frequently but such a long disease free interval as 12 years is quite uncommon.

Disease-Free Survival↗
PubMed2003

Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507.

Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.

Adult↗
PubMed2003

State-dependent activity of neurons in the perifornical hypothalamic area during sleep and waking.

Neurons containing orexins are located in the perifornical hypothalamic area and are considered to have a role in sleep-wake regulation. To examine how this area is involved in the regulation of sleep and wakefulness, we recorded neuronal activity in undrugged, head-restrained rats across sleep-waking cycles. Recordings were made in the perifornical hypothalamic area where orexin-immunoreactive neurons are distributed (PFH), and in the area dorsal to the PFH, including the zona incerta and subincertal nucleus (collectively referred to as ZI). The 40 neurons recorded from in the PFH were divided into five groups: (1) neurons most active during paradoxical sleep (PS, n=14, 35%), (2) neurons active during both waking (W) and PS (n=12, 30%), (3) neurons most active during W (n=7, 18%), (4) neurons most active during slow-wave sleep (SWS, n=3, 7.5%), and (5) neurons whose activity had no correlation with sleep-waking states (n=4, 10%). Of 30 neurons recorded from in the ZI, the corresponding numbers were 13 (43%), seven (23%), six (20%), three (10%), and one (3.3%). In both areas, neuronal activity fluctuated more during PS than during W. Waking-specific neurons (group 3) in the PFH generated action potentials with longer durations than those produced by other types of neurons. About half of the neurons in the PFH that were classified in groups 1, 2, and 3 increased their firing rate after the transition from one state to another, while higher percentages of neurons of groups 1 and 2 in the ZI than those in the PFH increased their firing rate prior to the state shift from SWS to PS. In these ZI neurons, however, the firing rate varied considerably at the state shift. These results suggest that the PFH and ZI are involved in the regulation of PS or W, especially the regulation of phasic events during PS or the maintenance of W. The ZI appears to be more closely involved than the PFH in the induction of PS or some phasic phenomena associated with PS.

Action Potentials↗
PubMed2003

Role of interleukin-12 in the regulation of CD4+ T cell apoptosis in a mouse model of asthma.

Allergic asthma, a chronic inflammatory disease of the airways, is characterized by the presence of T helper 2 cells and eosinophils in sputum, bronchoalveolar lavage, and mucosal biopsy specimens. Although the T helper 1-promoting cytokine, interleukin-12, is capable of inhibiting the T helper 2-driven asthma symptoms and bronchial responsiveness, the specific mechanisms underlying these interleukin-12 actions are unclear. The anti-allergic response to interleukin-12 is only partially dependent on interferon-gamma, which induces apoptosis by enhancing expression of Fas antigen. We therefore investigated in vivo whether the anti-allergic action of interleukin-12 is mediated through induction of apoptosis. C57BL/6 mice immunized to ovalbumin by intraperitoneal injection were challenged three times with an ovalbumin aerosol every second day for 7 days. Recombinant interleukin-12 was administered intravenously after the final challenge. After the last ovalbumin challenge, mice were examined for effects of interleukin-12 on inflammatory cell infiltration and apoptosis in the lung as detected by terminal deoxynucleotidyl transferase-mediated deoxyribonucleoside triphosphate nick end-labelling. Administration of interleukin-12 reduced ovalbumin-induced pulmonary eosinophilia (P < 0.01) and CD4+ T cell infiltration (P < 0.01). Moreover, treatment with interleukin-12 shortly after ovalbumin inhalation resulted in both increased interferon-gamma production (P < 0.01) and enhanced apoptosis of CD4+ T cells in allergic airway infiltrates (P < 0.05). These results suggest that the beneficial effects of interleukin-12 in asthma may include enhancement of apoptosis of CD4+ T cells in airways.

Animals↗
PubMed2003

Clinicopathological analysis of 143 primary malignant lymphomas in the small and large intestines based on the new WHO classification.

AIM: To study the clinicopathological and immunohistochemical features of 143 cases of primary small and large intestinal non-Hodgkin's lymphoma (NHL) in Japanese patients who presented between 1981 and 2000. METHODS AND RESULTS: The new World Health Organization (WHO) classification was used to classify NHL. The patients included 109 males and 34 females, with an average age of 54.1 years. Tumour sites were as follows: ileocaecal (n = 51, 35.7%), ileum (n = 29, 20.3%), rectum (n = 13, 9.1%), and duodenum (n = 11, 7.7%). Macroscopically, 124 cases (86.7%) were classified as tumorous type, 12 (8.4%) as diffuse infiltration type (erosion, superficial ulceration), five (3.5%) as polyposis type, and only two cases (1.4%) as ulceration type. Immunohistochemically, 122 lesions (85.3%) were of B-cell phenotype and 21 lesions (14.7%) were of T-cell phenotype. According to the WHO classification, of the B-cell lymphomas, 84 cases (68.9%) were large cell, 16 (13.1%) were Burkitt, 10 (8.2%) were marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT), and seven (5.7%) were mantle cell tumours. Among the T-cell lymphomas, 15 (71.4%) were of unspecified type, two (9.5%) were natural killer type, two were anaplastic large-cell lymphomas, one was lymphoblastic, and one was an adult T-cell leukaemia lymphoma. The survival rate for T-cell lymphomas was poorer than for B-cell lymphomas. Among the B-cell lymphomas, mantle cell lymphoma tended to have a poorer prognosis, whereas MALT lymphomas had a better prognosis than other B-cell tumour types. CONCLUSIONS: Our retrospective study of patients with primary malignant lymphomas in the small and large intestines has illustrated the clinical features and outcomes of patients with this disease.

Adolescent↗
PubMed2003

Feasibility study using a new small electronic pancreatoscope: description of findings in chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Numerous images characteristic of chronic pancreatitis have been obtained with fiberoptic peroral pancreatoscopy systems. However, the resolution of these images is inferior to that obtained with peroral electronic pancreatoscopy (PEPS). Clearer images of the pancreatic duct with chronic pancreatitis have now been documented, in some cases using PEPS alone. The significance of this finding is reported here. PATIENTS AND METHODS: A total of 42 PEPS procedures were carried out in 36 patients with chronic pancreatitis, without sphincterotomy or balloon dilation of the papilla of Vater. Using endoscopic retrograde pancreatography, the patients were classified as having equivocal (n=5), mild (n=5), moderate (n=15), or marked (n=11) degrees of chronic pancreatitis. The insertion rate with PEPS was 90 % (38 of 42 procedures), and it was ultimately possible to examine five, three, 13, and 11 patients in each group, respectively. RESULTS: Images of turbid pancreatic juice, protein plugs of various shapes, pancreatic calculi, indistinct vascular markings, whitish mucosa, local redness, scattered redness, disappearance of the fold, deformation of the fold, irregularly dilated lumen, and stenosis were found to be characteristic of chronic pancreatitis. These images were obtained using PEPS. CONCLUSIONS: PEPS proved to be a feasible new technique for diagnosing chronic pancreatitis, and it was able to detect abnormal findings more clearly than other imaging methods.

Aged↗
PubMed2003

Distant failure after treatment of postoperative locoregional recurrence of non-small cell lung cancer.

BACKGROUND: The standard treatment for patients with locoregional recurrence of non-small cell lung cancer (NSCLC) after complete resection has not been established. The aim of this study was to evaluate clinicopathologic characteristics, type of locoregional recurrence, pattern of subsequent failure, and survival after the recurrence. METHODS: Of 743 patients undergoing pulmonary resection for NSCLC in the National Cancer Center Hospital between 1990 and 1995, we retrospectively reviewed the medical charts of the 43 patients (5.8 %) found to have locoregional recurrence without distant metastasis or pleural or pericardial involvement. RESULTS: The median time to locoregional recurrence was 13.6 months (range: 1.6 - 85.8 months). The most frequent site of recurrence was the mediastinal nodes in 21 of 43 patients (49 %). 33 patients (77 %) received further treatment for the recurrence: thoracic irradiation in 26, surgery in two, systemic chemotherapy in two, and a combination of the above in 3 patients. Subsequent distant failure was detected in 26 (68 %) of the 38 patients assessable for the analysis of failure pattern: lung in 11, brain in 6, bone in 5, and others in 13. The median interval from the recurrence to distant failure was 8.4 months (range: 1.7-56.4 months). The median survival time after diagnosis of the locoregional recurrence was 10.5 months (range: 0-74.0 months). A multivariate analysis showed that local therapy for the locoregional recurrence had no significant impact on postrecurrent survival or distant failure-free survival. CONCLUSIONS: Many patients with postoperative locoregional recurrence developed distant metastases early after the first recurrence. Systemic chemotherapy in addition to local therapy may be of benefit in this population.

Adult↗
PubMed2002

Effects of post-inhalation treatment with interleukin-12 on airway hyper-reactivity, eosinophilia and interleukin-18 receptor expression in a mouse model of asthma.

BACKGROUND: Correcting Th1/Th2 imbalance with administration of IL-12 before and during antigen challenge holds therapeutic promise in asthma. However, the effects of IL-12 on the established asthmatic responses have not fully been examined. OBJECTIVE: We investigated whether IL-12 administered after antigen challenge could diminish airway hyper-reactivity (AHR) and eosinophilia in mice actively sensitized to ovalbumin. We also have investigated the ability of administered IL-12 to induce IL-18 receptor (IL-18R) expression that may lead possible synergic action of IL-12 with endogenous IL-18. METHODS: C57BL/6 mice immunized to ovalbumin (OVA) by intraperitoneal (i.p.) injection, were challenged three times with an aerosol of OVA every second day for 8 days. Recombinant IL-12 (500 ng) was intravenously administered on a single occasion 1 h after the final challenge of mice. Mice were analysed for effects of IL-12 on AHR, inflammatory cell infiltration and cytokine levels in lung tissue as well as serum immunoglobulin (Ig) E levels. Immunohistochemistry for IL-18R was performed using rat monoclonal antibody specific for murine IL-18Ralpha (IL-1 receptor related protein; IL-1Rrp). RESULTS: An intravenous IL-12 administration diminished AHR, pulmonary eosinophilia and T lymphocyte infiltration, serum IgE, IL-4 and IL-13 in lung tissue. Expression of IL-18R was induced in the mononuclear cells in the lung of mice exposed to OVA. IL-12 administration enhanced the IL-18R expression compared with the control. CONCLUSION: These data indicate that IL-12 can attenuate established antigen-induced AHR and inflammation. In this mechanism it would be interpreted as follows: IL-12 administration in OVA-challenged mice decreased IL-4 production and IgE production thereafter through direct effect on inhibiting the activation of established Th2 cells response and also combined effect with up-regulation of IL-18R expression by inflammatory cells in the lung.

Administration, Inhalation↗
PubMed2002

Interferon retreatment reduces or delays the incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

Inhibition of hepatocarcinogenesis is a crucial issue in treating chronic hepatitis C patients, especially those who do not respond completely to interferon therapy. Interferon has been reported to reduce the incidence of hepatocellular carcinoma (HCC) not only in sustained virological responders but also in transient biochemical responders. However, the incidence of HCC increases in 5 years or more after interferon therapy in transient biochemical responders. The aim of this study is to assess whether interferon retreatment reduces the incidence of HCC in chronic hepatitis C patients in whom hepatitis C virus was not eradicated during initial interferon therapy. We enrolled 309 patients who were not sustained virological responders after initial interferon treatment consisting of a total dose of more than 250 megaunits of interferon and were followed for more than 2 years after treatment. Ninety-nine patients received interferon retreatment and 210 did not. Two courses of interferon therapy were administered in 84, three courses in 14 and five courses in one. The incidence of HCC was compared between patients with retreatment and those without. In the clinical characteristics, retreated patients were younger and followed up for a longer time period. The cumulative incidence of HCC was significantly lower in retreated patients. In multivariate analysis, patients' age (P=0.018) and the number of courses of interferon therapy (P=0.022) were independently associated with HCC incidence. These results suggest that interferon retreatment reduces or delays the incidence of HCC in chronic hepatitis C patients who did not completely respond to initial therapy.

Adult↗
PubMed2002

Analysis of glucose tolerance in twin gestations using an oral glucose load.

The effect of twin gestation on carbohydrate metabolism was evaluated using a 75 g oral glucose tolerance test (75 g OGTT). A 75 g OGTT was performed in 63 twin gestations and 3 791 singleton gestations during the third trimester. Plasma glucose concentrations were measured in the pregnant women under fasting conditions as well as 30 min, 1 h, and 2 h after ingestion of glucose (75 g oral load), and serum insulin concentrations were measured in fasting and 30 min post-ingestion samples. Women with twin gestations showed significantly lower plasma glucose concentrations during fasting and 30 min after the glucose load in the samples taken than those with singleton gestations. No significant difference in serum glucose concentrations was found in the other specimens. There were no cases of gestational diabetes mellitus in our study. Although women with twin gestations demonstrated lower plasma glucose concentrations than women with singleton gestations, the difference observed was subtle. We could not find any significant differences in these plasma glucose values as used to define a pathologic OGTT between twin and singleton pregnancies, with the exception of the fasting value.

Adult↗
PubMed2002

Relationship between objective responses in phase I trials and potential efficacy of non-specific cytotoxic investigational new drugs.

BACKGROUND: Although the evaluation of new investigational drugs in phase I, II and III trials requires considerable time and patient resources, only a few of these drugs are ultimately established as anticancer drugs. MATERIALS AND METHODS: We collected papers of phase I trials by a Medline search using the key words 'Neoplasms/Drug Therapy in MeSH' and 'Phase I' for the period from 1976 to 1993. A drug was defined as 'effective' if a regimen including the drug produced positive results in at least one phase III trial. We analyzed the relationship between objective (complete and partial) responses in phase I trials and the effectiveness of agents in phase III trials. RESULTS: A total of 399 single-agent phase I trials of cytotoxic agents in adult patients with solid tumors were obtained. Further clinical investigation was not recommended in 36 trials (9%) because of severe toxicity. In the remaining 363 trials, 174 drugs were evaluated and the median number of trials for each drug was two (range one to nine). Objective responses were observed in 495 (4.1%) of 12 076 patients, 178 (49%) of 363 trials, and 115 (66%) of 174 drugs. Of the 174 drugs, 48 (28%) were considered to be effective. Percentages of effective drugs rose as the number of responders in phase I trials increased. Logistic regression analyses showed the number of responders to be significantly associated with drug effectiveness [odds ratio = 1.16 (1.06-1.27), P = 0.001 for 174 drugs; odds ratio = 1.16 (1.05-1.28), P = 0.0038 for 363 trials]. Although 10 active drugs failed to produce an objective response in phase I trials, seven of them produced a tumor regression of <50%, and three reportedly produced objective responses in phase I trials conducted before 1975. The numbers of responders among patients with lung, ovarian, breast or colorectal cancer, but not those among patients with lymphoma, melanoma, sarcoma or renal-cell carcinoma, were associated significantly with drug effectiveness against the respective tumors. CONCLUSIONS: Objective responses observed in phase I trials are important for determining the future development of an anticancer drug.

Antineoplastic Agents↗
PubMed2001

Changes in monoamine release in the ventral horn and hypoglossal nucleus linked to pontine inhibition of muscle tone: an in vivo microdialysis study.

A complete suppression of muscle tone in the postural muscles and a reduction of muscle tone in the respiratory related musculature occur in rapid eye movement (REM) sleep. Previous studies have emphasized the role of glycine in generating these changes. Because the activity of norepinephrine- and serotonin-containing neurons is known to decrease in REM sleep, we hypothesized that a decrease in release in one or both of these transmitters might be detected at the motoneuronal level during muscle tone suppression elicited by brainstem stimulation in the decerebrate animal. We compared release in the ventral horn with that in the hypoglossal nucleus to determine whether the mechanism of muscle tone suppression differs in these nuclei as has been hypothesized. Electrical stimulation and cholinergic agonist injection into the mesopontine reticular formation produced a suppression of tone in the postural and respiratory muscles and simultaneously caused a significant reduction of norepinephrine and serotonin release of similar magnitude in both hypoglossal nucleus and spinal cord. Norepinephrine and serotonin release in the motoneuron pools was unchanged when the stimulation was applied to brainstem areas that did not generate bilateral suppression. No change in dopamine release in the motoneuron pools was seen during mesopontine stimulation-induced atonia. We hypothesize that the reduction of monoamine release that we observe exerts a disfacilitatory effect on both ventral horn and hypoglossal motoneurons and that this disfacilitatory mechanism contributes to the muscle atonia elicited in the decerebrate animal and in the intact animal during REM sleep.

Animals↗