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Biomedical subjects

Takashi Watanabe

Publications and source records attributed to Takashi Watanabe.

At least 37 records · Page 2Linked to original sources

Hydrocephalus after intraventricular hemorrhage in eclamptic woman with HELLP syndrome.

We report the first case of an obstructive hydrocephalus after intraventricular hemorrhage in a woman with HELLP syndrome and eclampsia. A 25-year-old primiparaous woman had severe preeclampsia at 36 weeks of gestation. She complained of epigastric pain and nausea. The levels of AST, ALT, and LDH were 539, 560, and 1051 IU/L, respectively; the platelet count was 101 x 109/L. Cesarean section was promptly performed. Intraoperatively, she had a first convulsion. The CT scan revealed only mild brain edema. The platelet count deteriorated to 30 x 109/L at 5 hour after the operation, and she had a second convulsion with an intraventricular hemorrhage. On the 6th post-cesarean day, she complained severe headache followed by coma. The CT scan revealed the enlargement of both lateral ventricles, indicating the occurrence of obstructive hydrocephalus. Drainage into cerebral ventricle was performed, resulting in the recovery of consciousness to a normal level.

Adult↗

A simple and sensitive method for detecting major mutations within the tyrosine kinase domain of the epidermal growth factor receptor gene in non-small-cell lung carcinoma.

The detection of mutations in the epidermal growth factor receptor (EGFR) gene impacts therapeutic decision-making for non-small-cell lung carcinoma (NSCLC). Although direct sequencing has been most frequently used to detect EGFR mutations, this method displays several disadvantages. We set up simple mutation-specific polymerase chain reaction (PCR) for common delE746-A750 and L858R mutations of EGFR using primers specific to these mutations. Both mutation-specific PCR and direct sequencing methods were used to investigate 62 samples of NSCLC, and the results were compared. To evaluate the sensitivity of mutation-specific PCR, DNA mixtures containing various proportions of mutant alleles were analyzed. Mutation-specific PCR revealed delE746-A750 in 8 samples and L858R in 14 samples. All samples with either delE746-A750 or L858R mutation revealed by direct sequencing also displayed positive results for mutation-specific PCR. Conversely, mutations in 3 samples revealed by L858R-specific PCR were barely detectable by direct sequencing. In DNA mixture analysis, DNA mixtures containing 2.5% of delE746-A750 allele or 0.25% of L858R allele yielded positive results with mutation-specific PCR. Our mutation-specific PCR showed satisfactory sensitivity and reliability for detecting major EGFR mutations in clinical NSCLC samples. Given the practical availability, this method could be widely applicable to the treatment of lung cancers.

Base Sequence↗

Randomized phase II study of concurrent and sequential rituximab and CHOP chemotherapy in untreated indolent B-cell lymphoma.

CHOP combined with rituximab (R-CHOP) is regarded as one of the most effective treatments for indolent B-cell non-Hodgkin lymphoma (B-NHL), however, its optimal combination schedule remains unknown. We performed a randomized phase II study to explore a more promising schedule in untreated, advanced indolent B-NHL. Patients were randomized to receive either six courses of CHOP concurrently with rituximab (Arm C), or six courses of CHOP followed by six courses of weekly rituximab (Arm S). A total of 69 patients received the concurrent (n=34) or sequential (n=35) regimen. Overall response rate (ORR) in Arm C was 94% (95% confidence interval [CI], 79 to 99), including a 66% complete response (CR) compared with 97% (95% CI, 85-100), including a 68% CR in Arm S. Patients in Arm C experienced more grade 4 neutropenia (85%versus 70%) and experienced more grade 3 or greater non-hematological toxicities (21%versus 12%). Both arms were tolerated well. With a median follow-up of 28.2 months, the median progression-free survival (PFS) time was 34.2 months in Arm C, and was not reached in Arm S. R-CHOP is highly effective in untreated indolent B-NHL, either concurrent or in a sequential combination. Both combination schedules deserve further investigation.

Adult↗

Diffuse large B-cell lymphoma presenting as a unilateral solitary round pulmonary hilar node infarction.

Unilateral solitary pulmonary hilar node adenopathy is a rare presentation of diffuse large B-cell lymphoma. In this report, the authors present a case with a solitary pulmonary hilar lymph node infarction caused by diffuse large B-cell lymphoma. Enhanced CT examinations revealed a well-defined round mass with homogenous low attenuation in the left pulmonary hilum. Both radiological imaging and pathological examination can provide useful information for the interpretation of abnormalities and may enable the diagnosis of rare aetiologies.

Biopsy↗

Changes in plasma levels of hepatocyte growth factor and its associated factors during pregnancy.

AIM: Hepatocyte growth factor (HGF) was originally identified as a factor that stimulates the mitogenesis of hepatocyte, and also plays a role in maintaining pregnancy. We conducted this study to evaluate the changes in plasma concentrations of HGF and its associated factors during normal pregnancy. METHODS: Blood specimens were obtained from 14 healthy non-pregnant and 175 healthy pregnant and post-partum women (189 women in all). The women's plasma concentrations of total HGF, active HGF, active HGF activator (HGFA), HGF activator inhibitor type 1 (HAI-1) and HGF activator inhibitor type 2 (HAI-2) were determined by enzyme-linked immunosorbent assay. RESULTS: The levels of active HGF and HGF activator were significantly lower in pregnant women compared with those of non-pregnant women. The level of plasma HAI-1 significantly increased as pregnancy progressed, while it fell post-partum. Also, there were no differences in the concentrations of total HGF and HAI-2 in non-pregnant and pregnant women. CONCLUSION: A high concentration of HAI-1 during pregnancy may decrease the plasma level of active HGFA. This may in turn inhibit the activation of the precursor form of HGF, leading to a decrease in the level of plasma active HGF.

Adult↗

Relationship of hypotension and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Changes in systemic arterial blood pressure and the degree of cerebral vasospasm were investigated in 125 patients with aneurysmal subarachnoid hemorrhage. METHODS: Systemic arterial blood pressure was measured every 2 hours in each patient for a period of more than 2 weeks, and a fall in systemic blood pressure (FBP) was defined as a decrease of >40 mmHg of systolic blood pressure between two consecutive measurements. RESULTS: A total of 91 FBPs occurred in 52 (41.6%) of 125 patients despite specific post-operative management to prevent hypovolemia. Five (5.5%) of the 91 FBPs occurred just before the onset of symptomatic vasospasm. Symptomatic vasospasm was observed in 36 (69.2%) of 52 patients with FBP and in 32 (43.8%) of 73 patients without FBP (p<0.01, chi-squared test). A hypodense area on computed tomographic scans in association with cerebral vasospasm was observed in 25 (48.1%) of 52 patients with FBP and in 21 (28.8%) of 73 patients without FBP (p<0.05). DISCUSSION: We conclude that FBP might result from delayed cerebral vasospasm and/or brain dysfunction owing to subarachnoid hemorrhage itself.

Aged↗

Studies on nepalese crude drugs. XXVIII. Chemical constituents of Bhote Khair, the underground parts of Eskemukerjea megacarpum HARA.

From the underground parts of Eskemukerjea megacarpum HARA, two new stilbenes (14, 15) were isolated, together with a known coumarin, 5,7-dihydroxycoumarin (1), a tyramine derivative, trans-feruloyltyramine (2), two pyrogallol derivatives, gallic acid (3) and beta-glucogallin (4), four flavonoids, trifolin (5), hyperin (6), myricetin 3-O-beta-D-galactopyranoside (7), and myricitrin (8), five stilbenes, resveratorol (9), astringenin (10), piceid (11) astringin (12), and resveratorol 3-O-beta-D-(6-O-galloyl)glucopyranoside (13), a flavan-3-ol, (-)-epigallocatechin 3-O-gallate (16), two proanthocyanidins, catechin-(4alpha-->8)-epigallocatechin 3-O-gallate (17) and epicatechin 3-O-gallate-(4beta-->8)-epigallocatechin 3-O-gallate (18), and an anthocyanin, idaein (19). Compounds 14 and 15 were identified as (E)-3,5,3',4'-tetrahydroxystilbene 3-O-beta-D-(6-O-galloyl)glucopyranoside and (E)-3,5,4'-trihydroxystilbene 3-O-beta-D-(6-O-galloyl)glucopyranoside, respectively, based on spectral and chemical data.

Coumarins↗

Novel approach to calvarial bone transport using a rabbit model.

Calvarial defects sometimes require cranioplasty to protect the brain. Alloplastic materials, such as acrylic resin, hydroxyapatite ceramics, and titanium, involve various problems, such as vulnerability, infection, deformity resulting from growth, and high cost. We devised a new bone transport model in the rabbit based on the distraction osteogenesis theory of Ilizarov. Twelve Japan white rabbits with a mean body weight of 2.5 kg aged 12 weeks were used. Craniectomy (7 x 14 mm) was performed in 12 rabbits. Trapezoid bone osteotomy was performed anterior to the calvarial defect in 10 rabbits. The distraction device (Extension-plates) was fixed between the trapezoid bone island and the skull. Distraction was initiated 5 days postoperatively. The device was activated once every other day, with approximately 0.75 mm or 0.5 mm per activation. Bone distraction was continued until the rod could not be moved. The lengths of distraction were 4 mm in two cases, 5 mm in one case, 6 mm in one case, and 7 mm in two cases, with a mean of 5.5 +/- 0.56 mm. Both radiographic and histological findings showed osteogenesis by intramembranous ossification and trans-chondroid bone formation. Distraction osteogenesis has potential clinical applications in cranioplasty, especially in children because usage of autogenous bone is difficult if not impossible in most cases.

Animals↗

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2004)].

From October 2004 to September 2005, we collected the specimen from 319 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 383 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 381 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S. aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin-sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and inhibited the growth of all the strains at 2 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of all the strains at 0.125 microg/mL. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P. aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP, cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the growth of all the strains at 0.063 microg/mL. Also, all the agents generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (57.0%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H. influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae (16.1%) also were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria relatively frequently isolated from the patients treated with macrolides were P. aeruginosa and the isolation frequency was 43.5%.

Aged↗

Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin.

In humans, neurotrauma is suspected to cause brain atrophy and accelerate slowly progressive neurodegenerative disorders, such as Alzheimer's disease or schizophrenia. However, a direct link between brain injury and subsequent delayed global neurodegeneration has remained elusive. Here we show that juvenile (4-week-old) mice that are given a discrete unilateral lesion of the parietal cortex, develop to adulthood without obvious clinical symptoms. However, when monitored 3 and 9 months after lesioning, using high-resolution three-dimensional MRI and behavioural testing, the same mice display global neurodegenerative changes. Surprisingly, erythropoietin, a haematopoietic growth factor with potent neuroprotective activity, prevents behavioural abnormalities, cognitive dysfunction and brain atrophy when given for 2 weeks after acute brain injury. This demonstrates that a localized brain lesion is a primary cause of delayed global neurodegeneration that can be efficiently counteracted by neuroprotection.

Acute Disease↗

Phase II study of oral fludarabine phosphate in relapsed indolent B-Cell non-Hodgkin's lymphoma.

PURPOSE: Although intravenous (IV) fludarabine phosphate is effective against indolent B-cell non-Hodgkin's lymphoma (B-NHL), IV administration for 3 to 5 consecutive days is inconvenient in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine phosphate in patients with indolent B-NHL, we conducted a multicenter phase II study. PATIENTS AND METHODS: Patients with relapsed indolent B-NHL received fludarabine phosphate tablets orally once daily on days 1 through 5 every 28 days for three to six cycles. The efficacy was separately analyzed in a mantle-cell lymphoma (MCL) cohort and indolent B-NHL except for MCL (IL) cohort. The primary end point was the overall response rate (ORR). RESULTS: Fifty-two patients, including 46 in the IL cohort (41 with follicular lymphoma) and six in the MCL cohort, were registered, and all patients were eligible. Forty-one patients (79%) had received rituximab as prior therapy. In the IL cohort, the ORR and complete response rate were 65% (30 of 46 patients; 95% CI, 50% to 79%) and 30% (14 of 46 patients; 95% CI, 18% to 46%), respectively. One of six patients with MCL achieved a partial response. The median times to treatment failure for the 46 patients in the IL cohort and for the six patients in the MCL cohort were 8.6 and 6.1 months, respectively. Hematologic toxicities, including grade 4 neutropenia (37%), were the most frequent toxicities, and nonhematologic toxicities were mild. CONCLUSION: Oral fludarabine phosphate is highly effective in patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab and is more convenient than the IV formulation.

Administration, Oral↗

Tricyclic pharmacophore-based molecules as novel integrin alpha(v)beta3 antagonists. Part III: synthesis of potent antagonists with alpha(v)beta3/alpha(IIb)beta3 dual activity and improved water solubility.

In order to optimize our novel integrin alpha(v)beta3/alpha(IIb)beta3 dual antagonists, spatial screening at the N-terminus was performed. The alpha(v)beta3 antagonistic activity varied depending on the space that was occupied by the N-terminus, but high potency against alpha(IIb)beta3 was well maintained. The (3S)-aminopiperidine analogue had the strongest activity against alpha(v)beta3, and the S isomer at piperidine was more potent than the R isomer. Compounds selected on the basis of SAR analysis of a novel lead compound showed acceptable early absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles and sufficient water solubility for use as infusion drugs. Docking studies with the alpha(v)beta3 receptor were performed to confirm the SAR findings.

Animals↗

Methane fermentation of Japanese cedar wood pretreated with a white rot fungus, Ceriporiopsis subvermispora.

Methane fermentation of Japanese cedar wood was carried out after pretreatment with four strains of white rot fungi, Ceriporiopsis subvermispora ATCC 90467, CZ-3, CBS 347.63 and Pleurocybella porrigens K-2855. These fungi were cultivated on wood chip media with and without wheat bran for 4-8 weeks. The pretreated wood chip was fermented anaerobically with sludge from a sewage treatment plant. Pretreatments with C. subvermispora ATCC 90467, CZ-3 and CBS 347.63 in the presence of wheat bran for 8 weeks decreased 74-76% of beta-O-4 aryl ether linkages in the lignin to accelerate production of methane. After fungal treatments with C. subvermispora ATCC 90467 and subsequent 30-days methane fermentation, the methane yield reached 35 and 25% of the theoretical yield based on the holocellulose contents of the decayed and original wood, respectively. In contrast, treatment with the three strains of C. subvermispora without wheat bran cleaved 15-26% of the linkage and produced 6-9% of methane. There were no significant accelerating effects in wood chips treated with P. porrigens which has a lower ability to decompose the lignin. Thus, it was found that C. subvermispora, with a high ability to decompose aryl ether bonds of lignin, promoted methane fermentation of softwood in the presence of wheat bran.

Basidiomycota↗

Molecular breeding of white rot fungus Pleurotus ostreatus by homologous expression of its versatile peroxidase MnP2.

Using a DNA-mediated transformation technique, a molecular breeding approach to isolate Pleurotus ostreatus strains with enhanced productivity of its versatile peroxidase MnP2 was conducted. A recombinant mnp2 construct under the control of P. ostreatus sdi1 expression signals was introduced into the wild-type P. ostreatus strain by cotransformation with a carboxin-resistant marker plasmid. A total of 32 transformants containing the recombinant mnp2 sequence were isolated in a screening with specific amplification by PCR. Productivity of MnP2 in the recombinants was evaluated by the decolorization ability of Poly R-478 on agar plates in the absence of Mn2+. Recombinant P. ostreatus strains with elevated manganese peroxidase (MnP) productivity were successfully isolated. One of the recombinants, TM2-10, was demonstrated to secrete recombinant MnP2 predominantly on a synthetic medium containing 15 mM ammonium oxalate, which was confirmed by reverse transcription PCR (RT-PCR) and isozyme profile analysis using anion-exchange chromatography. The benzo[a]pyrene-removing activity by fungal treatment was also analyzed using the isolated recombinant strains.

Benzopyrenes↗

Novel serum tumor marker, RCAS1, in pancreatic diseases.

AIM: As tumor markers for pancreatic carcinoma, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been used, but the sensitivity and specificity are not enough for the diagnosis of pancreatic carcinoma. METHODS: A novel serum tumor marker, RCAS1, was compared with two conventional serum tumor markers, CEA (highly specific for pancreatic cancer) and CA 19-9 (highly sensitive for pancreatic cancer), in 48 patients with pancreatic exocrine tumors. RESULTS: When the diagnosis of benign or malignant conditions was examined by one tumor marker, the sensitivity of RCAS1 alone (55%) was higher than that of CEA alone (27%) and the specificity of RCAS1 alone (92%) was greater than that of CA19-9 alone (78%). When examined by a combination of two markers, the sensitivity of a combination of RCAS1 and CA19-9 (95%) was superior to those of CA19-9 alone (78%), RCAS1 alone (55%, P = 0.002), CEA alone (27%) (P<0.001), RCAS1 and CEA (59%) and CA19-9 and CEA (82%). CONCLUSION: These results suggest that the combination of RCAS1 and CA19-9 is highly sensitive for pancreatic carcinoma.

Adult↗