Childhood cutaneous natural killer/T lymphoma successfully treated with only one course of chemotherapy and incomplete tumor resection.
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Biomedical subjects
Publications and source records attributed to M Okada.
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In this study, we demonstrated that toremifene citrate (TOR) inhibited the tube formation and migration of human umbilical vein endothelial cells (HUVEC) in vitro. Moreover, TOR suppressed angiogenesis in rabbit cornea and lung metastasis of human fibrosarcoma HT-1080 cells in nude mice. The antiangiogenic activity in vitro was apparent at the concentration of 5 microM which is clinically achievable by oral administration of 120 mg/kg of TOR. These results suggest that clinical treatment with 120 mg/day of TOR might be expected to exhibit antiangiogenesis and antimetastasis effects, in addition to inhibition of estrogen-dependent tumor cell growth.
From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.
Health statistics is an essential element to improve the ability of managers of health institutions, healthcare researchers, policy makers, and health professionals to formulate appropriate course of reactions and to make decisions based on evidence. To ensure adequate health statistics, standards are of critical importance. A study on healthcare statistics domain analysis is underway in an effort to improve usability and comparability of health statistics. The ongoing study focuses on structuring the domain knowledge and making the knowledge explicit with a data element dictionary being the core. Supplemental to the dictionary are a domain term list, a terminology dictionary, and a data model to help organize the concepts constituting the health statistics domain.
We considered treatment for recurrence following the resection of hepatic metastases from colorectal cancer. The subjects of this study were 15 of 29 patients who had undergone WHF arterial infusion following resection of hepatic metastases from colorectal cancer, in whom there was a recurrence. Of these 15 cases, 6 involved recurrence in a single organ (residual liver, 4; lung, 1; local area, 1), 7 involved two organs (residual liver and lung, 2; residual liver and local area, 2; residual liver and bone, 1; spleen and intra-abdominal lymph node, 1; intra-abdominal lymph node and peritoneum, 1) and 2 involved three organs (lung, bone and abdominal wall, 1; lung, peritoneum and distal lymph node, 1). Reresection was performed in all cases in which recurrence occurred in a single organ. For those cases in which recurrence occurred in two or more organs, reresection and infusion were performed in the 4 cases of recurrence in the residual liver and reresection was performed in the case of recurrence in the spleen and intra-abdominal lymph node (No. 16), the case of local recurrence and the case involving the abdominal wall. The 5-year survival rate of the 29 cases who underwent initial hepatic resection was 61.9%. Five years following resection, the recurrence rate in the residual liver was 38.3%. The survival rates following treatment for recurrence were 76.9, 51.3 and 25.6% for 1, 3 and 5 years, respectively. Of the 8 deaths which have occurred to date, only one was directly related to an increase in hepatic metastases. Following resection of hepatic metastases from colorectal cancer, WHF provides a high rate of prevention as well as a high survival rate. Furthermore, with regard to recurrence following WHF treatment, if the recurrence is in only one organ, there is the possibility of achieving effective treatment by reresection (WHF = 5-FU 1,000 mg/m2 5 hrs qw).
OBJECTIVES: Angioplasty for the unprotected left main trunk remains controversial, but new procedures and devices such as directional coronary atherectomy and stenting have improved the results. We compared the results of angioplasty with the inflexible balloon and new devices. METHODS: The procedures were performed in 239 consecutive lesions in 160 patients between April 1986 and March 2000. This study excluded emergency cases and repeat angioplasty cases, and included 120 initial and elective cases. Initial and long-term results were compared between the balloon group (n = 29) and the new device group (n = 91). RESULTS: Lesion success rate was lower in the balloon group (90% vs 100%, p < 0.05), but there were no significant differences in in-hospital results including cardiac death (0% vs 0%), noncardiac death (0% vs 3.3%), Q-wave myocardial infarction (0% vs 2.2%), non-Q wave myocardial infarction (3.4% vs 6.6%), bypass surgery (0% vs 0%) and repeat angioplasty (6.9% vs 1.1%). Quantitative angiography showed significant improvements in minimal lumen diameter (mean 2.17 vs 3.16 mm, p < 0.001) and percentage diameter stenosis (mean 31% vs 13%, p < 0.001) in the new device group after the procedures. The minimum lumen diameter remained larger at 3 (p < 0.001) and 6 months (p < 0.05) in the new device group. Therefore, angiographic restenosis rate was higher in the balloon group (55% vs 21%, p < 0.005). Five-year survival rate showed no significant difference between the groups (75.0% vs 83.8%). CONCLUSIONS: New devices significantly improved the minimal lumen diameter after angioplasty for unprotected left main trunk disease, and lead to significant improvement of restenosis rate at follow-up.
OBJECTIVE: To investigate the application and effect of laparoscopic splenectomy (LS) in the treatment of spleen diseases. METHODS: Under CO2 pneumoperitoneum, laparoscopic splenectomy was performed on 43 patients. General conditions before and after operation, platelet counting, complications and recovery of patients were studied. RESULTS: Laparoscopic splenectomy was performed without complications in all the patients. In the patients with ITP, the effective rate of LS was 89.3%. The difficulty of operation was identified when the diameter of the spleen was over 15 cm assessed by ultrasonic examination, and the operative time was usually prolonged. CONCLUSIONS: LS is one of the best choices when proper indications exist and good techniques under laparoscopy are provided.
The purpose of this study is to assess the effects of physical training on autonomic nervous function. Twenty-two healthy subjects(12 males and 10 females) participated in this study. We inquired contents of the exercise for each subject. Continuous ECG was recorded during 320 seconds at supine resting. Respiratory rhythm was fixed at 0.25 Hz(15 time/min). On the basis of spectral analysis of heart rate variability, the autonomic nervous function was assessed by low frequency power(LF: 0.06-0.13 Hz) and high frequency power(HF: 0.16-0.50 Hz). The predominance of sympathetic nervous activity were indicated by the LF/HF and LF-HF. Relationship between physical training and autonomic function was analyzed by using multivariate analysis(partial correlation analysis). As the results, LF power and LF-HF negatively correlated with training time per day, energy expenditure per day, energy expenditure per week, and total energy expenditure, respectively(p < 0.05). HF power positively correlated with energy expenditure per day, energy expenditure per week, and total energy expenditure, respectively(p < 0.05). These results indicate not training time but energy expenditure alters the autonomic nervous function. This index may be useful for evaluating training effect on the promotion of health.
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Clinical assessment of platelet scintigraphy by using autologous platelet labeled with 111-indium oxine to detect thrombotic activity for deep vein thrombosis. Platelet accumulation on scintigrams had a tendency to correlate with aggravation of acute thrombotic symptoms in deep vein thrombosis. This method was a useful procedure to make early diagnosis of deep vein thrombosis by detecting of abnormal accumulation of platelet. In addition, appropriate thrombolytic and anticoagulant therapy resulted in reduced platelet accumulation in conjunction with improvement of acute clinical symptoms. Thus, platelet scintigraphy could be available to evaluate thrombotic activity and might be useful for determining the optimal indications of thrombolytic and anticoagulation therapies for acute deep vein thrombosis. On the other hand, another kind of scintigraphy might be inevitable especially for detection of the pulmonary embolism. Anticoagulation therapy is also effective for pulmonary embolism.
Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the first and rate-limiting enzyme of the hexosamine biosynthesis pathway, which plays an important role in glucose toxicity and cellular insulin resistance. Thus, the mechanisms by which GFAT expression is regulated under physiological and pathological conditions are of interest in connection with diabetes. In this study, we cloned the 5'-flanking region of the mouse GFAT2 gene and characterized its promoter activity. Sequence analysis revealed several putative regulatory elements Sp1, a CCAAT box, AP-1 and AP-2, but no TATA box. Transfection experiments showed that the 5'-flanking region between -2462 to +38 relative to the transcription start site of the GFAT2 gene drives transcription in NIH3T3 cells and that the fragment from -141 to -9 has the highest transcription activity. Reporter assays using deletion and mutant variants suggested that the Sp1 sites at positions -83 to -78 and -22 to -17 both play an important role in the basal promoter activity of the mouse GFAT2 gene. Electrophoretic mobility shift assay showed DNA-protein binding at both Sp1 sites. We also compared the promoter activities of mouse GFAT1 and GFAT2 in several cell lines.
Among three period genes (per1, per2, per3) in mammals, only per2 gene was shown to be involved in the core clock mechanism. To elucidate the molecular function of rat PERIOD2 (rPER2), we searched for binding proteins to the PAS domain of rPER2. We isolated a binding protein to this domain and identified it as a TIMELESS-like protein (TLP) on the basis of mass analyses. Then, we isolated a rat TLP cDNA from the rat hypothalamus library. RNA blot analysis and in situ hybridization indicates that rTLP mRNA was expressed in all rat tissues from whole brain, the suprachiasmatic nucleus, eye, lung, heart, liver, kidney, placenta, and testis. When rTLP gene product was expressed in COS-1 cells, nuclear localization of rTLP was detected in 99.6% of transfected cells. These results suggest that the interaction of rPER2 with rTLP may influence the regulation of circadian clock components in nucleus after rPER2 is translocated into the nucleus.
A new monoclonal antibody (MAb), 22-1-1, acts against a novel tumor-associated antigen (Ag) strongly expressed in human uterine cervical adenocarcinomas. A cDNA encoding the Ag recognized by the 22-1-1 MAb has been isolated and called RCAS1 (receptor-binding cancer antigen expressed on SiSo cells). RCAS1 can induce growth arrest and apoptosis in RCAS1 receptor-positive cells including T cells and natural killer cells in vitro. These results suggest that RCAS1 is involved in tumor escape from the immune system. Immunohistochemical analysis revealed the relationship between RCAS1 expression and clinicopathological variables (age, sex, smoking, histology, differentiation grade, pathological T factor, N factor and stage) and the prognostic significance of RCAS1 in 66 lung-cancer patients who underwent curative operations: 33 adenocarcinomas, 24 squamous-cell carcinomas, 3 large-cell carcinomas, 4 adenosquamous carcinomas and 2 small-cell carcinomas. Median follow-up period of 64 non-small-cell carcinomas (NSCLCs) was 67.4 months. RCAS1 was expressed in 74.2% of lung cancers. RCAS1 in NSCLC cases with advanced T factor or pathological stage or in poorly differentiated adenocarcinomas was highly expressed. Furthermore, RCAS1 expression inducing apoptosis of tumor-infiltrating lymphocytes was a significant prognostic factor in NSCLC (p<0.03).
To explore the pathogenesis of benign familial neonatal convulsions (BFNC), we determined effects of KCNQ-related M-channels (KCNQ-channels) on hippocampal glutamate (Glu) and gamma-aminobutyric acid (GABA) releases using microdialysis, and propagation of evoked field-potentials (FP) using multielectrode (64-ch)-dish system as two-dimensional monitoring. KCNQ-channel inhibitor, Dup996, enhanced hippocampal K(+)-evoked Glu and GABA releases without affecting basal releases of them. Dup996 unaffected FP-amplitude, but enhanced FP-propagation. The GABA(A)-receptor antagonist, bicuculline, enhanced the stimulatory effects of Dup996 on FP-propagation, however, this stimulatory effects of Dup996 were abolished by the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/glutamate-receptor antagonist, DNQX. These results suggest that the occurrence of BFNC cannot be produced by KCNQ-channel dysfunction alone, but by reciprocal action between impaired KCNQ-channel and other unknown elements (possibly dysfunction of inhibitory neurotransmission system).
A high-performance liquid chromatographic (HPLC) procedure based on an isocratic elution with photodiode array detection has been developed for a simple and rapid determination of ellagic acid (EA) in fresh and processed fruits. The homogenized sample was refluxed with methanol and then the extract was refined using a solid-phase cartridge before HPLC. We analyzed EA in 40 kinds of fresh fruits and 11 kinds of processed fruits by the developed method. EA was found in several berries, fueijoa, pineapple and pomegranate. This is the first occurrence of the detection of EA in bayberry, fueijoa and pineapple.
Recently discovered mammalian clock genes are believed to compose the core oscillator, which generates the circadian rhythm. BMAL1/CLOCK heterodimer is the essential positive element that drives clock-related transcription and self-sustaining oscillation by a negative feedback mechanism. We examined BMAL1 protein expression in the rat suprachiasmatic nuclei (SCN) by immunoblot analysis. Anti-BMAL1 antiserum raised against rBMAL1 recognized 70 kDa mBMAL1b and detected a similar immunoreactivity (IR) as a major band in rat brains. Robust circadian BMAL1-IR oscillations with nocturnal peaks were detected in the SCN during a light/dark cycle and under constant darkness. A short duration light exposure at night acutely reduced BMAL1-IR in the SCN during photoentrainment. This might be attributable to the degradation of BMAL1 protein. Application of glutamate and NMDA to the SCN slices at projected night, a procedure mimicking photic phase delay shift, also acutely reduced BMAL1-IR in a similar manner. A rapid decrease of BMAL1 protein suggests that BMAL1 protein might be implicated in the light-transducing pathway within the SCN.
Csk (carboxyl-terminal Src kinase) is a cytoplasmic tyrosine kinase that phosphorylates a critical tyrosine residue in each of the Src family kinases (SFKs) to inhibit their activities. Recently, we identified a transmembrane protein, Cbp (Csk-binding protein), that, when phosphorylated, can recruit Csk to the membrane where the SFKs are located. The Cbp-mediated relocation of Csk to the membrane may play a role in turning off the signaling events initiated by SFKs. To further characterize the Csk-Cbp interaction, we have generated a reconstituted system using soluble, highly purified proteins. Csk and phosphorylated Cbp were co-purified as a large protein complex consisting of at least four Csk.Cbp units. The addition of the phosphorylated, but not nonphosphorylated, Cbp to an in vitro assay stimulated Csk activity toward Src. Csk was also activated by a phosphopeptide containing the tyrosine in Cbp that binds to Csk (Tyr-314). Kinetic analysis revealed that Cbp or the phosphopeptide induced up to a 6-fold reduction in the K(m) for Src, indicating that the Csk.Cbp complex has a greater affinity for Src than free Csk. These findings suggest that Cbp is involved in the regulation of SFKs not only by relocating Csk to the membrane but also by directly activating Csk.
A simple and rapid analytical method of five phenolic acids, gallic, chlorogenic, caffeic, ellagic and ferulic acid, which are naturally occurring bioactives, were determined in fruit juices by isocratic LC using photodiode array UV detection. The sample was pre-treated by solid-phase extraction (a combination of Sep-Pak Plus tC18 and Bond Elut PSA).