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Biomedical subjects

Toshiaki Tanaka

Publications and source records attributed to Toshiaki Tanaka.

At least 37 records · Page 2Linked to original sources

Retroperitoneal extragonadal germ cell tumor presenting as a bulky pelvic mass of the obturator fossa.

Extragonadal germ cell tumors (EGGCT) are commonly found in the midline of the body. We report a rare case of a retroperitoneal EGGCT presenting as a bulky pelvic mass located between the left internal and external iliac arteries in a 29-year-old man. His alpha-fetoprotein level was 12946.2 ng/mL and the biopsy of the tumor revealed a nonseminomatous germ cell tumor. After three cycles of chemotherapy (bleomycin/etoposide/cisplatin) followed by resection of all residual tumors, one cycle of salvage chemotherapy (etoposide/ifosphamide/cisplatin) was added. The patient was disease free at 21-month follow up.

Adult↗

Effect of growth hormone treatment on trunk fat accumulation in adult GH-deficient Japanese patients: a randomised, placebo-controlled trial.

OBJECTIVE: Patients with growth hormone deficiency (GHD), both Japanese and Caucasian, have an abnormal body composition with pronounced abdominal obesity. This study aimed to evaluate changes in trunk fat with GH treatment. DESIGN: Double-blind, placebo-controlled study. PATIENTS AND MEASUREMENTS: Sixty-one Japanese adult GH deficient patients (mean age 37 years) were randomised to either GH, titrated to 0.012 mg/kg/day, (n = 30) or placebo (n = 31) for 24 weeks. Body composition, by dual-energy X-ray absorptiometry (DXA), was evaluated at a central laboratory for trunk fat, total body fat and lean body mass. Serum lipid levels were also determined centrally. RESULTS: At baseline, 26 (42.6%) patients had a body mass index (BMI) > or = 25 kg/m(2), the threshold for obesity-related complications for Japanese subjects. Median trunk fat mass (FM) was > or = 9.0 kg for each treatment and gender group, higher than the cut-off for increased age-adjusted risk for cardiovascular complications reported in the normal Japanese population. After 24 weeks of GH treatment, the change in percentage trunk FM was -3.4 +/- 0.6%, versus 0.4 +/- 0.6% with placebo (p < 0.001). Change in total body FM was -2.8 +/- 0.5% with GH and 0.0 +/- 0.5% with placebo, indicating that the decrease in trunk fat was more pronounced than for total body fat. Total and low density lipoprotein (LDL)-cholesterol were both significantly (p < 0.001) decreased compared with placebo. One patient discontinued due to a subdural haematoma and one had GH dose reduced due to hyperglycaemia. CONCLUSIONS: Japanese patients with GHD have abnormal central fat accumulation, which is reduced by GH treatment over 24 weeks. This may reduce cardiovascular risk but the GH dose should be individualised to maintain IGF-I in the normal range.

Abdominal Fat↗

Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency: questionnaire study on the data registered with the foundation for growth science, Japan.

In this study, we sent questionnaires to doctors treating severe short stature with severe GH deficiency (GHD) (height SDS (HtSDS) below -4 and all peak GH to provocative stimuli below 2 micro/L) (abbreviated as Severe Case), and obtained effective replies of 51 cases. The clinical characteristics, etiologies, and pathophysiology of these patients were examined. Among the 51 Severe Cases no consanguinity was observed, 44 were IGHD (24 males and 20 females), 3 were GH-1 gene deletion, 2 were Pit-1 gene mutation, and 2 were achondroplasia. HtSDS in these Severe Cases was already remarkably low at 12 (-3.0) and 24 months old (-3.9), while their birth weight and birth length were within normal ranges. Among 44 patients with IGHD, 12 were isolated GHD, and the remaining 32 were combined pituitary hormone deficiency (CPHD). Pituitary MRI was undergone in 25 idiopathic GHD, and abnormal findings (pituitary atrophy, interruption of stalk, and ectopic posterior lobe) were observed in 21 patients with CPHD. More than half of these patients had the history of breech delivery. Three patients with GH-1 gene mutation showed normal pituitary MRI, whereas one of two patients with Pit-1 mutation showed pituitary atrophy and narrowing of pituitary stalk. In conclusion, Severe Cases tended to have CPHD, and the incidence of Severe Case was only 0.6% of total IGHD. Although GHD due to genetic disorders is considered to be extremely rare (0.06% of total IGHD), the incidence reaches high levels (9.8%) among Severe Cases. Growth disorders in these Severe Cases seem to occur soon after delivery. Much earlier diagnosis and hGH treatment are desirable to attain better final height in the Severe Cases. GH-1 and Pit-1 gene analyses are crucial, when genetic abnormalities other than achondroplasia are suspected.

Achondroplasia↗

Molecular genetic analysis of MODY candidate genes in Japanese patients with non-obese juvenile onset diabetes mellitus.

We analyzed 84 Japanese patients with juvenile-onset (before 18 years of age) non-obese diabetes mellitus (DM) for mutations in the genes for HNF-1alpha, HNF-4alpha and HNF-1beta. In HNF-1alpha, previously reported mutations (R271W and R272C) and one novel sequence variant (at nucleotide -129/-130 insTTGGGG of the promoter region) were identified in three different patients. In vitro functional study of the new promoter variant demonstrated that the transcriptional activity was 1.6-2.0 times higher than that of the wild-type. This may lead to overexpression of HNF-1alpha and subsequent negative regulation of the target genes of HNF-1alpha. No mutation was identified in the HNF-4alpha and HNF-1beta genes. In this study on a small series of non-obese Japanese patients with juvenile-onset DM, the prevalence of MODY3 was 3.5%. The significance of the new promoter variant in the development of DM is unclear; however, a promoter mutation in the HNF-1alpha gene could be diabetogenic.

Adolescent↗

[Clinical pathways in the treatment of cancers].

At the beginning, a clinical pathway was first introduced for the purpose of standardizing the treatment, providing high quality management and shortening hospital stays in the managed care health system in USA. This has been rapidly accepted also in Japan. The clinical pathway has also been gradually introduced in the treatment of malignant diseases, including chemo/radiotherapy and surgery. In Kurume University Hospital, clinical pathways are now applied for 50% of inpatients, and those for cancer patients have a large role in routine clinical practice. The progress of our pathways for cancer patients is here reported.

Critical Pathways↗

Bladder perforation of the tension-free vaginal tape detected with a flexible cystoscope.

A 67-year-old woman who presented with stress urinary incontinence underwent a tension-free vaginal tape (TVT) operation. Postoperatively, she complained of urgency, gross hematuria and dysuria, which persisted for one week. Cystoscopy with a flexible cytoscope revealed penetration of the bladder wall by the tape, which had been missed during the TVT procedure by rigid cystoscopy. After the penetrating portion of the tape was excised, her symptoms were resolved and continence was preserved. This case suggests that employment of a flexible cytoscope is useful to detect the placement of tape in the bladder wall, which may be missed with a rigid cytoscope.

Aged↗

A preliminary study of clinical assessment of left unilateral spatial neglect using a head mounted display system (HMD) in rehabilitation engineering technology.

PURPOSE: Unilateral spatial neglect (USN) is a common syndrome in which a patient fails to report or respond to stimulation from the side of space opposite a brain lesion, where these symptoms are not due to primary sensory or motor deficits. The purpose of this study was to analyze an evaluation process system of USN in various visual fields using HMD in order to understand more accurately any faults of USN operating in the object-centred co-ordinates. METHOD: Eight stroke patients participated in this study and they had Left USN in clinical test, and right hemisphere damage was checked by CT scan. Assessments of USN were performed the BIT common clinical test (the line and the stars cancellation tests) and special tests the zoom-in condition (ZI) condition and the zoom-out condition (ZO) condition. The subjects were first evaluated by the common clinical test without HMD and then two spatial tests with HMD. Moreover, we used a video-recording for all tests to analyze each subject's movements. RESULTS: For the line cancellation test under the common condition, the mean percentage of the correct answers at the left side in the test paper was 94.4%. In the ZI condition, the left side was 61.8.% and the right side was 92.4.%. In the ZO condition, the left side was 79.9% and the right side was 91.7.%. There were significant differences among the three conditions. The results of the stars cancellation test also showed the same tendency as the line bisection test. CONCLUSION: The results showed that the assessment of USN using a technique of HMD system may indicate the disability of USN more than the common clinical tests. Moreover, it might be hypothesized that the three dimensional for USN test may be more related to various damage and occurrence of USN than only the two dimensional test.

Journal Article↗

Film thickness and fluidity of various luting cements determined using a trial indentation meter.

OBJECTIVES: The purpose of this study was to evaluate a new trial apparatus which could measure film thickness (T(h)) under a low load, using an indenter. METHODS: Five commercial luting cements were measured using this apparatus. T(h) was determined using four kinds of indenter, which were 5.0, 10.0, 15.0 and 20.0mm in diameter. For each indenter, the load per contact area of the indenter with the platen equaled 150N per 200 mm2 described in ISO No. 9917. The effects of working time (30, 60, and 90 s) and load (2.86, 6.78, 10.7, and 14.7N) on the fluidity and T(h) were examined using the indenter with a diameter of 5.0mm. The duration of loading was 10 min. The fluidity was defined as the reciprocal of the apparent viscosity and was calculated using Stefan's equation. RESULTS: The T(h) obtained using this apparatus agreed with the film thickness obtained using the test described in ISO No. 9917. For Durelon (DU), T(h) increased 1.58 times and fluidity decreased 0.26 times as the working time increased from 30 to 90 s; T(h) decreased 0.56 times and fluidity increased 1.28 times as loading increased from 2.86 to 14.7N. For Ketac cement radiopaque (KE), Panavia fluoro cement (PA), Scotchbond resin cement (SC), and Vitremer luting cement (VI), although the fluidity and T(h) were not influenced much by duration (30-90 s), T(h) decreased 0.79, 0.74, 0.95, and 0.78 times for KE, PA, SC, and VI, respectively, and fluidity decreased 0.68, 0.51, 0.30, and 0.36 times, respectively, as loading increased from 2.86 to 14.7N. SIGNIFICANCE: This apparatus was proven effective in elucidating the flow properties of luting cement.

Composite Resins↗

Hepatocyte growth factor induces redistribution of p21(CIP1) and p27(KIP1) through ERK-dependent p16(INK4a) up-regulation, leading to cell cycle arrest at G1 in HepG2 hepatoma cells.

Hepatocyte growth factor (HGF) has an anti-proliferative effect on many types of tumor cell lines and tumors in vivo. We found previously that inhibition of HGF-induced proliferation in HepG2 hepatoma cells is caused by cell cycle arrest at G1 through a high intensity ERK signal, which represses Cdk2 activity. To examine further the mechanisms of G1 arrest by HGF, we analyzed the Cdk inhibitor p16(INK4a), which has an anti-proliferative function through cell cycle arrest at G1. We found that HGF treatment drastically increased endogenous p16 levels. Knockdown of p16 with small interfering RNA reversed the arrest, indicating that the induction of p16 is required for G1 arrest by HGF. Analysis of the promoter of the human p16 gene identified the proximal Ets-binding site as a responsive element for HGF, and this responded to the high intensity ERK signal. HGF treatment of the cells led to a redistribution of p21(CIP1) and p27(KIP1) from Cdk4 to Cdk2. The redistribution was blocked by the knockdown of p16 with small interfering RNA, which restored the Cdk2 activity repressed by HGF, demonstrating the requirement of p16 induction for the redistribution and eventual repression of Cdk2 activity. Our results reveal a signaling pathway for G1 arrest induced by HGF.

Carcinoma, Hepatocellular↗

Long-term functional outcome and late complications of Studer's ileal neobladder.

OBJECTIVE: The purpose of this study was to evaluate the long-term functional outcome and late complications of Studer's ileal neobladder. METHODS: The study included 57 patients who underwent radical cystectomy and bladder reconstruction with Studer's ileal neobladder, and were followed-up for at least 3 months after surgery. The voiding and storage function, and late complications were evaluated. The times of evaluation after surgery were categorized into periods I (3-23 months), II (24-59 months), III (60-95 months) and IV (> or =96 months). RESULTS: Daytime and night-time continence rates were 95.6 and 88.6%, respectively. The averages of functional capacity (439 ml), maximum flow rate (15.7 ml/s) and residual urine (35 ml) evaluated in period I were maintained in period IV. Of the 57 patients, intermittent self-catheterization was needed in five (8.8%) due to incomplete emptying or urinary retention. Urethroileal anastomotic stricture was found in two patients (3.5%), who were successfully treated by transurethral intervention. Inguinal hernia was found in seven patients (12.8%), five of whom developed it within 2 years after surgery. CONCLUSIONS: Our results indicate that Studer's ileal neobladder had a favorable long-term functional outcome. Although late complication rates were low, the incidence of inguinal hernia was relatively high, and this was considered as a definite late complication in our study.

Adult↗

Prospective non-randomized trial comparing esophagectomy-followed-by-chemoradiotherapy versus chemoradiotherapy-followed-by-esophagectomy for T4 esophageal cancers.

BACKGROUND AND OBJECTIVES: Multimodal treatment is commonly adopted for patients with a T4 esophageal cancer. This trial evaluated which therapy offered a better survival: preoperative chemoradiotherapy (CRT) or postoperative CRT. METHODS: Forty-three patients with a T4 esophageal cancer were enrolled in a prospective study in which each patient decided for themselves a treatment arm, CRT-followed-by-esophagectomy or esophagectomy-followed-by-CRT. The CRT-followed-by-esophagectomy Group received 36 Gy radiotherapy and simultaneous chemotherapy using cisplatin (CDDP) and 5-fluorouracil (5FU) preoperatively, and then 24 Gy radiotherapy and simultaneous chemotherapy using CDDP and 5FU postoperatively. The esophagectomy-followed-by-CRT Group received 60 Gy radiotherapy with two cycles of simultaneous chemotherapy using CDDP and 5FU postoperatively. RESULTS: Of 26 patients who chose CRT-followed-by-esophagectomy, 15 (58%) underwent esophagectomy, while 7 (27%) refused surgery and 4 (15%) were inoperable. Of 17 patients who chose esophagectomy-followed-by-CRT, 14 (82%) underwent esophagectomy, while 3 (18%) underwent inspection thoracotomy. The CRT-followed-by-esophagectomy Group showed a significantly better 5-year-survival rate than the esophagectomy-followed-by-CRT Group (26% vs. 0%). Multivariate analysis demonstrated that only the response to CRT was prognostic. CONCLUSIONS: This trial concluded that the first choice of treatment for patients with a T4 esophageal cancer was prior CRT rather than prior esophagectomy.

Aged↗

Activators of AMP-activated protein kinase enhance GLUT4 translocation and its glucose transport activity in 3T3-L1 adipocytes.

To determine whether the increase in glucose uptake following AMP-activated protein kinase (AMPK) activation in adipocytes is mediated by accelerated GLUT4 translocation into plasma membrane, we constructed a chimera between GLUT4 and enhanced green fluorescent protein (GLUT4-eGFP) and transferred its cDNA into the nucleus of 3T3-L1 adipocytes. Then, the dynamics of GLUT4-eGFP translocation were visualized in living cells by means of laser scanning confocal microscopy. It was revealed that the stimulation with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) and 2,4-dinitrophenol (DNP), known activators of AMPK, promptly accelerates its translocation within 4 min, as was found in the case of insulin stimulation. The insulin-induced GLUT4 translocation was markedly inhibited after addition of wortmannin (P < 0.01). However, the GLUT4 translocation through AMPK activators AICAR and DNP was not affected by wortmannin. Insulin- and AMPK-activated translocation of GLUT4 was not inhibited by SB-203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK). Glucose uptake was significantly increased after addition of AMPK activators AICAR and DNP (P < 0.05). AMPK- and insulin-stimulated glucose uptake were similarly suppressed by wortmannin (P < 0.05-0.01). In addition, SB-203580 also significantly prevented the enhancement of glucose uptake induced by AMPK and insulin (P < 0.05). These results suggest that AMPK-activated GLUT4 translocation in 3T3-L1 adipocytes is mediated through the insulin-signaling pathway distal to the site of activated phosphatidylinositol 3-kinase or through a signaling system distinct from that activated by insulin. On the other hand, the increase of glucose uptake dependent on AMPK activators AICAR and DNP would be additionally due to enhancement of the intrinsic activity in translocated GLUT4 protein, possibly through a p38 MAPK-dependent mechanism.

2,4-Dinitrophenol↗

Esophagectomy: is it necessary after chemoradiotherapy for a locally advanced T4 esophageal cancer? Prospective nonrandomized trial comparing chemoradiotherapy with surgery versus without surgery.

The need for surgery after chemoradiotherapy for a T4N0-1M0 squamous cell carcinoma in the thoracic esophagus was evaluated. A series of 53 patients were enrolled in this prospective nonrandomized trial from among 124 patients with an esophageal cancer assessed as T4 in Kurume University Hospital from 1994 to 2002. After the first chemoradiotherapy cycle, which consisted of radiotherapy in a total dosage of 36 Gy and chemotherapy using cisplatin (CDDP) and 5-fluorouracil (5FU), the patients each decided, after being informed of the efficacy of the chemoradiotherapy, whether to undergo surgery. All patients, including those who had undergone surgery and those who had not, later underwent a second chemoradiotherapy cycle consisting of radiotherapy in a total dosage of 24 Gy and chemotherapy using CDDP and 5FU, as far as practicable. Among the responders to the first chemoradiotherapy cycle, there was no significant difference in the long-term (5-year) survival rate between the 18 patients who underwent esophageal surgery and the 13 patients who did not (23% vs. 23%). Among the nonresponders, the 11 patients who underwent surgery showed a tendency toward longer survival than the five patients who had had no surgery. The nonresponders had 1- and 2-year survival rates of 64% and 33%, respectively. The corresponding rates for the 5 nonsurgical patients who completed the two chemoradiotherapy cycle were 20% and 20%, respectively. For a T4N0-1M0 squamous cell carcinoma in the thoracic esophagus, full-dosage chemoradiotherapy (definitive chemoradiotherapy) is preferred for responders to a half-dose of chemoradiotherapy as much as esophagectomy, whereas esophagectomy may be preferred for nonresponders.

Antineoplastic Combined Chemotherapy Protocols↗

Relationships between erectile dysfunction, depression, and anxiety in Japanese subjects.

AIMS: This study aimed to elucidate the relationships between erectile dysfunction (ED) and depression or anxiety. METHODS: Subjects were 1,419 Japanese men aged 40-64 years. ED was assessed by the International Index of Erectile Function 5 (IIEF-5) score (Japanese version), and depression and anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS). In this study ED cases were defined as those whose IIEF-5 value was less than 12, and a score of 8 or higher was used to classify a subject as suffering from depression or anxiety, respectively. The prevalence odds ratio (OR) of ED was calculated with confidence interval (CI) estimated by the Woolf's method by five age groups (40-44, 45-49, 50-54, 55-59, 60-64 years). To control for age, body mass index, smoking, and alcohol drinking factors, we conducted the multivariate logistic regression analysis for calculating adjusted ORs and 99% CIs. RESULTS: ED was significantly associated with depression in age groups 45-49 (OR 3.42, 99% CI 1.51-7.76) and 50-54 years (OR 2.43, 99% CI 1.11-5.35). After using multivariate analysis, adjusted OR also showed statistical significance. (OR 2.02, 99% CI 1.32-3.08). ED was significantly associated with anxiety in the 50-55-year-old age group (OR 2.48, 99% CI 1.12-5.47). After using multivariate analysis, adjusted OR also showed statistical significance (OR 1.77, 99% CI 1.15-2.72). The concomitant depression and anxiety group (A+D+) had significantly higher prevalence of ED than the control group (A-D-) in both the 45-49 and 50-54 age groups. (P < 0.01) CONCLUSION: ED associated significantly with depression and anxiety status only in late 40s to early 50s (45-55 years) in male Japanese. Furthermore, comorbidities of depression and anxiety strengthen this association. Our results might be useful in furthering understanding of ED etiology and determining a target population for prevention in ED subjects.

Adult↗

A nationwide attempt to standardize growth hormone assays.

The Growth Hormone (GH) and Its Related Factors Study Committee of the Foundation for Growth Science, Japan, has been conducting a quality control study for 15 years to improve the equality of diagnosis of GH deficiency. It found that the greatest differences in measured GH values were due to the different potencies of the kit standards, which were primarily adjusted to WHO standards for human GH of pituitary origin. With the collaboration of kit makers and the Study Group of Hypothalamo-Pituitary Disorders of the Ministry of Health, Labor and Welfare, all GH kits in Japan have begun using the same recombinant human GH standard since April 2005. As a result the diagnostic cut-off peak GH has changed from 10 to 6 ng/ml.

Adolescent↗