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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 181 records · Page 10Linked to original sources

2-Alkynyl-8-aryl-9-methyladenines as novel adenosine receptor antagonists: their synthesis and structure-activity relationships toward hepatic glucose production induced via agonism of the A(2B) receptor.

Novel adenosine antagonists, 2-alkynyl-8-aryl-9-methyladenine derivatives, were synthesized as candidate hypoglycemic agents. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. In general, aromatic moieties at the 8-position and alkynyl groups at the 2-position had significantly increased activity compared to unsubstituted compounds. The preferred substituents at the 8-position of adenine were the 2-furyl and 3-fluorophenyl groups. In modifying the alkynyl side chain, change of the ring size, cleavage of the ring, and removal of the hydroxyl group were well tolerated. The order of the stimulatory effects of adenosine agonists on rat hepatocytes was NECA > CPA > CGS21680, which is consistent with involvement of the A(2B) receptor. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, one of the compounds potent in hepatocytes, 15o (IC(50) = 0.42 microM), antagonized NECA-induced stimulation of cyclic AMP production (IC(50) = 0.063 microM). This inhibitory effect was much more potent than those of FK453, KF17837, and L249313 which have been reported to be respectively A(1), A(2A), and A(3) selective antagonists. These findings agree very well with the result that, compared to 15o, these selective antagonists for each receptor subtype showed only marginal effects in rat hepatocytes. These results suggest that adenosine agonist-induced glucose production in rat hepatocytes is mediated through the A(2B) receptor. Furthermore, 15o showed hypoglycemic activity in an animal model of noninsulin-dependent diabetes mellitus, the KK-A(y) mice. It is possible that inhibition of hepatic glucose production via the A(2B) receptor could be at least one of the mechanisms by which 15o exerts its in vivo effects. Further elaboration of this group of compounds may afford novel antidiabetic agents.

Adenine↗

Dietary restriction impairs neutrophil exudation by reducing CD11b/CD18 expression and chemokine production.

HYPOTHESIS: Patients with malnutrition are susceptible to infection. Polymorphonuclear neutrophils (PMNs) are the major effector of the nonspecific immune response in host resistance to infection. Dietary restriction may impair PMN-mediated immunity in the peritoneal cavity by reducing PMN exudation, adhesion molecule expression on PMNs, and chemokine production. DESIGN: Randomized study of murine glycogen-induced peritonitis with dietary restriction. SETTING: University research laboratory. MATERIALS: Male C57BL/6J mice. INTERVENTIONS: Mice (N = 204) were assigned to ad libitum, moderate, and severe diet-restricted groups receiving mouse chow ad libitum (132 g/kg, 66 g/kg, and 33 g/kg daily for 7 days, respectively). After dietary restriction with or without 1 day of refeeding, mice were administered glycogen intraperitoneally to induce cell exudation. MAIN OUTCOME MEASURES: CD11b, CD18, and CD62L expressions on circulating PMNs, phagocytosis, and reactive oxygen intermediate production by exudative PMNs were measured after glycogen installation. The levels of PMN-specific chemokine, macrophage inflammatory protein 2 (MIP-2), in peritoneal lavage fluid were also measured. These parameters were measured after glycogen installation in the refeeding experiment. RESULTS: Seven days of dietary restriction decreased CD11b/CD18 expression on circulating PMNs, MIP-2 levels in peritoneal lavage fluid, and subsequent PMN exudation into the peritoneal cavity early in peritonitis. Both CD11b and CD18 expression on circulating PMNs and MIP-2 levels correlated significantly with numbers of exudative PMNs. Seven days of dietary restriction also impaired phagocytosis, while up-regulating reactive oxygen intermediate production by exudative PMNs. Only 1 day of ad libitum refeeding normalized CD11b/CD18 expression with PMN exudation into the peritoneal cavity. CONCLUSIONS: Short-term dietary restriction impairs PMN exudation into local inflammatory sites in murine peritonitis by reducing CD11b/CD18 expression and MIP-2 production. Even brief nutritional replenishment in diet-restricted patients may improve host defense via restoring these PMN functions and chemokine production at local inflammatory sites.

Animals↗

Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: outcomes of late effects on pituitary function and growth in long-term survivors.

It is well known that prophylactic cranial irradiation is highly effective in preventing central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL). Nevertheless, there have been very few reports on the late effects, especially pituitary function and growth, in long-term survivors who were treated with 18 Gy cranial irradiation in childhood. The subjects consisted of 35 children with ALL who were treated with prophylactic 18 Gy cranial irradiation at Kanagawa Children's Medical Center between October 1981 and February 1995. All patients received cranial irradiation after first attaining complete remission with induction chemotherapy, according to the treatment protocols prescribed by the Tokyo Children's Leukemia Study Group (TCLSG) and Tokyo Children's Cancer Study Group (TCCSG). Their ages at the time of cranial irradiation ranged from 2.2-15.0 years (mean 6.8). We evaluated their pituitary functions by measuring their pituitary hormone values 0.7-11.3 years (mean 6.0) after cranial irradiation and their growth by analyzing their height standard deviation score (SDS) at diagnosis of ALL and their final height SDS at the mean follow-up period of 8.2 years after cranial irradiation. Height SDS is defined as the difference between the patient's height and the mean height of their age and sex, divided by the standard deviation of their age and sex. Eight of 35 patients had ALL relapse, involving the bone marrow in seven patients and the CNS in only one. Six of the eight patients with relapse died 1.5-6.6 years after cranial irradiation and the other two patients were salvaged by further intensive therapies. The remaining 27 relapse-free patients have survived for 1.4-15.8 years (mean 10.1) after cranial irradiation. Twenty-six of the 29 survivors are long-term survivors of more than 5 years. Although there was one patient with an abnormal result in each value of growth hormone (GH), adrenocorticotropic hormone (ACTH), and prolactin (PRL), and two patients with abnormal results in thyroid-stimulating hormone (TSH) values, none of the patients had clinical symptoms of pituitary hormone abnormality and none required hormone supplements. The final height SDS decreased significantly compared with the height SDS at diagnosis of ALL in the long-term survivors (P = 0.001) and the height SDS of the patients who had received cranial irradiation at a young age tended to decrease gradually (P = 0.019). However, no patient showed severe growth failure. It is considered that prophylactic 18 Gy cranial irradiation plus chemotherapy for ALL in childhood can effectively prevent CNS relapse and is unlikely to produce clinically significant late effects, although it may cause slight pituitary hormone abnormality.

Adolescent↗

Gene transfer into cultured mammalian embryos by electroporation.

To gain a better understanding of mammalian development at the molecular level, technology is needed that allows the transfer of exogenous genes into desired embryonic regions at defined stages of development. Our strategy has been to use electroporation (EP) of plasmid DNA following whole-embryo culture (WEC). In our gene transfer system, postimplantation rodent embryos are taken out of the uterus and a purified DNA solution of mammalian expression plasmid constructs is injected into the neural tube. A square-pulse current is delivered using an electroporator with an optimizer. Electroporated embryos are allowed to develop in the WEC system for 24--48 h. Within the targeted area, the proportion of transfected cells varied from 10% to approximately 100% depending on the test conditions (e.g., DNA concentration, voltage, duration of EP, and pulse number). The EP--WEC system has several advantages including rapid gene expression, minimal laboratory work, precisely targeted regions, and no risk for human beings. Application of the method is useful in improving our understanding of early neural development (E7--E12 in mice), e.g., alteration of gene function via ectopic expression, interference with dominant negative proteins, and fate mapping with marker genes. In addition, EP can complement genetic approaches such as the generation of knockout and transgenic mice.

Animals↗

Right ventricular dynamic cardiomyoplasty for the univentricular heart with pulmonary hypertension.

OBJECTIVES: We conducted an acute experimental study to test the feasibility of dynamic cardiomyoplasty in a setting of modified Fontan procedure for univentricular heart with pulmonary hypertension to obtain a possible proxy for high-risk Fontan candidates. METHODS: After electrical preconditioning of the left latissimuss dorsi for 6 weeks in 8 dogs, the right ventricular cavity was totally obliterated with concomittent closure of the tricuspid valve and right pulmonary artery. Modified Fontan circulation was established with the aortic homograft anastomosed between the right atrium and pulmonary trunk, incorporated with a pericardial pouch as a compression chamber (neoright ventricle) fixed onto the epicardial surface of the ventricle. After cardiopulmonary bypass termination, a latissimus dorsi was applied to wrap the pericardial pouch and ventricle clockwise and stimulated with a trained-pulse (25 Hz) at 1:1 synchronization ratio with cardiac beats. RESULTS: Profound right heart failure was noted during Fontan circulation in increased pulmonary vascular resistance (11 +/- 3.2 Wood units), whereas graft pacing showed significant augmentation of systolic pulmonary pressure by 54 +/- 12%, the mean pulmonary flow by 68 +/- 23%, and aortic pressure by 23 +/- 5% at a physiological range of central venous pressure (13.2 +/- 0.7 mmHg). Right heart function curve analysis confirmed marked augmentation of right heart performance, restoring almost normal pulmonary circulation. These functional benefits were sustained up to 4 hours in 4 animals until experiments were terminated. CONCLUSIONS: Dynamic cardiomyoplasty in a modified Fontan procedure is a viable surgical option for univentricular heart, not a Fontan candidate.

Animals↗

Acquired storage-pool disorders occurring late after allogeneic bone marrow transplantation: partial activation of platelets in asymptomatic patients.

Bone marrow transplantation (BMT) may be complicated by coagulation abnormalities. The present study evaluated whether platelets might be activated in patients who had undergone BMT without significant coagulopathy. The patients selected had received allogeneic BMTs a median of 39 months before the study (range, 11-124 months) and had not received cyclosporine, FK506 (tacrolimus), or other medication affecting cyclo-oxygenase for at least 3 months prior to the collection of blood samples. Furthermore, patients had platelet counts greater than 100 x 10(9) cells/L and normal serum creatinine levels. Twenty-five healthy volunteers acted as controls. Platelet aggregation studies and a mepacrine assay of platelets showed abnormal aggregation and decreased staining in some patients. The platelet storage-pool adenosine 5'-triphosphate (ATP) level in 15 patients after BMT was 0.45+/-0.24 micromol per 10(11) platelets, whereas the level in 18 controls was 1.03+/-0.36 micromol per 10(11) platelets (P = .00078). The total ATP levels of platelets in patients and controls were 4.33+/-1.14 and 5.63+/-1.51 micromol per 10(11) platelets, respectively (P = .016). With the exception of 1 patient, plasma levels of thrombomodulin and von Willebrand factor were all within the normal range. The average plasma level of 11-dehydrothromboxane B2 was significantly increased in 15 patients after BMT compared with controls, 20.6+/-8.2 and 10.3+/-1.2 pg/mL, respectively (P = .0004). These findings suggest a long-term process of platelet activation in patients after BMT and, following the cessation of cyclosporine, development of acquired storage-pool disorder of platelets.

Adenosine Triphosphate↗

A basic study on lesion detectability for hot spot imaging of positron emitters with dedicated PET and positron coincidence gamma camera.

The aim of this study was to explore the correlations of detectability and the semi-quantification for hot spot imaging with positron emitters in positron emission tomography (PET) and with a positron coincidence detection system (PCD). Phantom study results for the measurement of the lesion-to-background (L/B) ratio ranged from 2.0 to 30.3, and detectability for hot spot lesion of PET and PCD were performed to correspond to clinical conditions. The detectability and semi-quantitative evaluation of hot spots from 4.4 mm to 36.9 mm in diameter were performed from the PET and PCD images. There were strong correlations between the L/B ratios derived from PET and PCD hot spot images and actual L/B ratios; but the L/B ratio derived from PET was higher than that from PCD with a significant difference of 10% to 54.8%. The detectability of hot spot imaging of PCD was lower than that of PET at 64.8% (PCD) versus 77.8% (PET). Even the actual L/B ratio was 8.0, hot spots more than 10.6 mm in diameter could be clearly identified with PCD imaging. The same identification could be achieved with PET imaging even when the actual L/B ratio was 4.0. This detailed investigation indicated that FDG PCD yielded results comparable to FDG PET on visual analysis and semi-quantitative analysis in detecting hot spots in phantoms, but semi-quantitative analysis of the L/B ratio with FDG PCD was inferior to that with FDG PET and the detectability of PCD in smaller hot spots was significantly poor.

Gamma Cameras↗

Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy.

Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p < 0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p < 0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r = 0.80, p < 0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclist's heart.

3-Iodobenzylguanidine↗

The usefulness of brain perfusion SPECT in an infant with focal convulsions associated with hemophilus influenzae central nervous system infection.

Left hemiconvulsions occurred in a 13-month-old girl with Hemophilus influenzae (H. influenzae) central nervous system (CNS) infection. Tc-99m HMPAO brain SPECT showed a focal hyperperfusion area in the right frontal lobe. The patient recovered without complications, and follow-up SPECT revealed markedly improved findings. Tc-99m HMPAO brain SPECT is useful for evaluating focal convulsions associated with H. influenzae CNS infection.

Brain↗

The role of whole-body FDG-PET in preoperative assessment of tumor staging in oral cancers.

OBJECTIVE: The aim of this study is to clarify the clinical utility of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) in determining the TNM classification in patients with oral cancer. METHODS: Twenty-five consecutive patients (14 male and 11 female; age range, 40 yr to 86 yr) with oral cancer were included in this study. The diagnostic accuracy for detecting cervical lymph nodes was investigated by comparing the results of CT and/or MRI and physical findings. For the semi-quantitative analysis, the tumor standardized uptake value (SUV) and tumor to background SUV ratio (T/B ratio) were assessed in primary tumors and cervical lymph nodes. RESULTS: All primary lesions were visualized on FDG-PET images. Even though artifacts from dental materials near the lesion hampered the delineation of primary tumors on CT/MRI, the extent of primary tumors was accurately assessed by FDG-PET. The SUV and T/B ratio in the primary tumor classified in higher T grade (T3 and T4) was significantly higher than that in lower T grade (T1 and T2) (mean +/- SD of SUV; 8.32 +/- 2.99 vs. 5.15 +/- 3.77, p < 0.01, mean +/- SD of T/B ratio; 6.96 +/- 3.23 vs. 3.61 +/- 2.76, p < 0.01). The SUV and T/B ratio of metastatic lymph nodes were also significantly higher than those of normal lymph nodes (mean +/- SD of SUV; 3.39 +/- 1.69 vs. 1.55 +/- 0.57, p < 0.001, mean +/- SD of T/B ratio; 2.46 +/- 1.08 vs. 1.03 +/- 0.22, p < 0.001). Among these three methods, FDG-PET in conjunction with CT/MRI showed the highest accuracy of 92%, but there were no significant differences in diagnostic accuracy among the three methods. For the semi-quantitative analysis, a threshold SUV of 2.0 provided 100% sensitivity, 82% specificity, and 88% accuracy. Furthermore, a threshold T/B ratio of 1.5 provided 100% sensitivity, 100% specificity, and 100% accuracy. Regarding the detection of distant metastasis, there was one positive result in FDG-PET showing distant pulmonary metastasis. CONCLUSIONS: Whole-body FDG-PET is an effective and convenient diagnostic tool for the evaluation of tumor staging in patients with oral cancer. Tumor staging by whole-body FDG-PET may, in fact, supplement the conventional staging by means of CT/MRI and physical findings.

Adult↗

Usefulness of dual-head coincidence gamma camera with thick NaI crystals for nuclear oncology: comparison with dedicated PET camera and conventional gamma camera with thin NaI crystals.

AIM: A comparative study of the images obtained with a dual-head coincidence gamma camera with thick NaI crystals (19 mm), a dedicated PET camera with BGO crystals and a conventional gamma camera with thin NaI crystals (9.5 mm) was conducted to clarify the clinical feasibility of a dual-head coincidence gamma camera with thick NaI crystals. METHODS: FDG images of 27 patients with malignant tumors were obtained by means of a dual-head coincidence gamma camera with thick NaI crystal and a dedicated PET camera with BGO crystals. The images of bone scintigraphy in 10 cancer patients obtained with the dual-head coincidence gamma camera were compared with those taken by a conventional dual-head gamma camera with thin NaI crystals. RESULTS: Patient-basis sensitivity in 27 patients with neoplasms and lesion-basis sensitivity of the dual-head coincidence gamma camera and the dedicated PET camera were 74.1% and 85.2% (n.s.), 66.7% and 72.2% (n.s.), respectively. The tumor to background FDG uptake ratio derived from the coincidence gamma camera was significantly lower than that derived from the dedicated PET camera (mean +/- s.d.; 3.48 +/- 3.77 vs. 8.12 +/- 8.92, p < 0.0001), but the tumor to background FDG uptake ratio obtained with both methods correlated well (r = 0.84, p < 0.001). Similar whole body bone scans were obtained with the dual-head coincidence gamma camera and the conventional dual-head gamma camera in all 10 patients. CONCLUSION: These results suggest that the dual-head coincidence gamma camera with thick NaI crystals has potentially high clinical applicability for community hospitals.

Adult↗

Central neurocytoma with unusually intense FDG uptake: case report.

Central neurocytoma is a benign neuronal tumor with a favorable prognosis. This tumor is typically characterized by decreased uptake of 18F-fluorodeoxy glucose (FDG) and any increased uptake of FDG in patients suffering from this tumor would be highly unusual. A case of central neurocytoma with an intense FDG uptake, combined with atypical histopathological features and a high proliferation index is reported in this paper. A 45-year-old male had a two months' history of right hemiweakness. Magnetic resonance (MR) imaging showed a large tumor in the right lateral ventricle. Positron emission tomography (PET) with FDG revealed high glucose metabolism in the tumor. The histological diagnosis was central neurocytoma with atypical features characterized by microvascular proliferation. The MIB-1 labeling index, ordinarily smaller than 2.0%, was 7.0%. Conventional radiotherapy, with a total dose of 50 Gy, was administered after the surgical treatment. The patient returned to his normal daily activities after the cessation of radiation therapy.

Cerebral Ventricle Neoplasms↗

Epidural anesthesia with lidocaine reduces propofol injection pain.

PURPOSE: To determine whether epidural lidocaine reduces the severity of propofol injection pain compared with iv lidocaine. METHODS: A prospective, randomized double-blind clinical study was conducted in 120 female patients scheduled for elective gynecological laparotomy. A lumbar epidural catheter and an iv catheter placed in the cephalic vein of the non-dominant hand were used in all patients. Patients of the control group (Group C) were given epidural normal saline followed by iv normal saline then iv propofol. Patients of Group E were given epidural 2% lidocaine (0.08 mL.cm(-1)) followed by iv normal saline and then propofol. Patients of Group V were given epidural normal saline followed by iv 2% lidocaine (0.05 mL.kg(-1)) then propofol. Pain was scored as no pain=0, minimal pain=1, moderate pain=2, severe pain=3. RESULTS: The pain scores, in group E; 1 (0-2) and group V; 2 (0-2), were significantly lower than in group C; 2 (1-3); median (25th-75th percentile) (P <0.001). There was no difference in pain score between groups E and V The plasma lidocaine concentration 15 min after epidural lidocaine was 2.74 +/- 0.54 microg.ml(-1), compared with 1.54 +/- 0.31 microg.mL(-1) at three minutes after iv lidocaine. CONCLUSION: Epidural and iv lidocaine equally reduced the severity of propofol injection pain despite higher lidocaine plasma concentrations in epidurally administered lidocaine.

Adult↗

Transgene expression of thioredoxin (TRX/ADF) protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hematotoxicity.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has a variety of toxic effects on a number of organs, including the hematopoietic system. The importance of TCDD-induced oxidative stress has been evaluated in several target organs. However, its role in hematotoxicity remains poorly understood, although bone marrow is known to produce reactive oxygen species. The aim of this study is to evaluate not only the contribution of oxidative stress to TCDD-induced hematotoxicity but also the protective function of TRX/ADF, a known anti-oxidative stress agent, on the hematotoxicity of TCDD in ADF wild-type (WT) and transgenic (Tg) mice. WT and Tg mice received a single intraperitoneal injection of 20 microg TCDD/kg. One day after the treatment, blood and bone marrow cellularity was measured and bone marrow levels of granulotyce/macrophage colony-forming units were determined in the in vitro colony assay. The expression of human TRX transgene by their bone marrow cells was analyzed by Western blot electrophoresis. Our results showed that overexpression of TRX/ADF protects against TCDD-induced hematotoxicity, indicating that induction of oxidative stress that results in disruption of redox regulation may be an important mechanism in TCDD-induced bone marrow toxicity. Moreover, we detected a significant decrease of AhR mRNA levels in bone marrow cells of Tg mice following TCDD treatment, suggesting a biological role of TRX/ADF in the AhR-mediated pathway through which TCDD induces oxidative stress.

Animals↗

Reproducibility of the brain perfusion index for measuring cerebral blood flow using technetium-99m compounds.

We previously developed an alternative method for estimating the brain perfusion index (BPI) using technetium-99m compounds and spectral analysis (SA) for quantification of cerebral blood flow (CBF). In this study, we investigated the reproducibility of the BPI values obtained by SA (BPIS) using a double injection of technetium-99m ethyl cysteinate dimer without any intervention, and compared it with that of the BPI values obtained by graphical analysis (BPIG). The BPIS values in the first (x) and second sessions (y) correlated closely (y=0.921x+0.036; r=0.962; n=64; s.e.e.=0.058 min-1). Although the BPIG values in the first (x) and second sessions (y) also correlated (y=0.942x+0.040; r=0.916; n=64; s.e.e.=0.061 min-1), the correlation coefficient for BPIS was significantly higher than that for BPIG. The reproducibility was dependent on the injection dose ratio of the second session to the first (R). The difference in BPI between the first and second sessions tended to be smaller when 1.5<R<2.5 than when 0<R<1.5 or 2.5<R. These results suggest that the reproducibility of BPIS is satisfactory and that it can be applied to two sequential measurements of CBF using a double injection of 99mTc compounds. When applying our method to such measurements, it is recommended that R is taken as approximately 2.0.

Aged↗

Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging.

The purpose of this study was to assess the clinical potential of methyl-11C-choline (11C-choline) in the diagnosis of brain tumours. To this end, the results of 11C-choline positron emission tomography (PET) in 22 patients suspected of having brain tumours were compared with the findings of contrast-enhanced magnetic resonance (MR) imaging and fluorine-18 fluorodeoxyglucose PET. A histopathological diagnosis was made for each patient during open surgery. The standardised uptake values of brain tumours and the tumour-to-white matter count (T/W) ratios were determined. The degree of 11C-choline accumulation noted in PET images was compared with the gadolinium-enhanced areas of MR images. The mean T/W ratio of 11C-choline in high-grade gliomas was found to be higher than that in low-grade gliomas. This difference was statistically significant (mean+/-SD: 8.7+/-6.2, n=9 versus 1.5+/-0.7, n=5, P<0.03) when data pertaining to the prominent uptake of 11C-choline in a patient with a pilocytic astrocytoma were excluded. 11C-choline PET failed to detect non-neoplastic lesions in two patients. Areas of 11C-choline accumulation in PET scans were larger than areas enhanced on MR images in five cases involving high-grade gliomas. 11C-choline PET differentiated between low-grade gliomas and high-grade gliomas, but did not differentiate between low-grade gliomas and non-neoplastic lesions. The combination of 11C-choline PET and MR imaging may provide investigators with an accurate means by which to identify high-grade gliomas.

Adolescent↗

Virus-associated hemophagocytic syndrome due to rubella virus and varicella-zoster virus dual infection in patient with adult idiopathic thrombocytopenic purpura.

A 26-year-old woman with idiopathic thrombocytopenic purpura (ITP) was admitted to our hospital because of fever and rash. Blood tests revealed thrombocytopenia, liver dysfunction, coagulopathy, and hyperferritinemia. Bone marrow examination revealed many atypical lymphocytes and some histiocytes with hemophagocytosis. On admission she was diagnosed with rubella virus-associated hemophagocytic syndrome (VHAS), but on laboratory examination, she was seropositive for varicella-zoster virus (VZV)-IgM as well as rubella virus-IgM. She was therefore diagnosed with dual infection by rubella virus and VZV. Her simultaneous rubella virus and VZV infection may have been related to the VAHS pathogenesis. She was treated with prednisolone and gamma globulin therapy and recovered completely.

Adult↗

The new antirheumatic drug KE-298 suppresses monocyte chemoattractant protein (MCP)-1 and RANTES production in rats with adjuvant-induced arthritis and in IL-1beta-stimulated synoviocytes of patients with rheumatoid arthritis.

We analyzed the effects of the new antirheumatic drug KE-298 on monocyte chemoattractant protein (MCP)-1 and regulated on activation normal T-cell expressed and secreted (RANTES) production in rats with adjuvant-induced arthritis and in interleukin (IL)-1beta-stimulated rheumatoid arthritis (RA) synoviocytes. In rats with adjuvant-induced arthritis, the enhanced production of MCP-1 and RANTES and the development of arthritis were suppressed by oral treatment with 100 mg/kg per day of KE-298 for 18 days. Furthermore, KE-298 (10-100 microg/ml) suppressed MCP-1 and RANTES production by IL-1beta-stimulated RA synoviocytes through inhibition of NF-kappaB and AP-1 activation. These results suggest that the inhibitory effect of KE-298 on MCP-1 and RANTES production might partly explain its efficacy in rats with adjuvant-induced arthritis and in patients with RA.

Aged↗