Biomedical subjects

Takashi Watanabe

Publications and source records attributed to Takashi Watanabe.

At least 127 records · Page 7Linked to original sources

PubMed2003

Characteristics of the gastric pH profiles of unfed and fed cynomolgus monkeys as pharmaceutical product development subjects.

Gastric pH is an important factor which significantly affects the dissolution of drugs, and therefore their bioavailability. In this study, the gastric pHs were measured directly with a miniature pH electrode inserted through the nostril into the body of the stomach of cynomolgus monkeys. Results from three separate sets of measurements using the same male monkeys indicated that the median gastric pH profiles of unfed monkeys were low, fluctuating between pH 1 and pH 3. However, the median gastric pHs in fed monkeys given about 108 g of a biscuit-type solid food, which are commonly provided, shifted toward a more neutral range between pH 5 and pH 7, and remained in this range for about 9 h. This result contrasted with reported results for humans after eating a standard meal, which showed a neutral range between pH 5 and pH 7 for a brief period. Consequently, these results indicate that although the gastric pH of unfed cynomolgus monkeys is similar to that of fasting humans, there is a great difference in the gastric pH profiles between humans and monkeys after eating, which suggests that further studies are needed to establish optimal feeding conditions for bioavailability studies in monkeys.

Animals↗

PubMed2003

Gastrointestinal transit of liquids in unfed cynomolgus monkeys.

In this study, the gastric emptying rate and oro-caecal transit time of two liquid volumes (20 and 60 ml) were compared in unfed cynomolgus monkeys. First, the acetaminophen method was used to determine the gastric half-emptying time (t(50%)). The mean t(50%) from seven monkeys was 21.2 min for the 20-ml volume and 27.8 min for the 60-ml volume. This mean t(50%) in monkeys is similar to that reported previously in fasting humans. Next, the sulfasalazine-sulfapyridine method was used to determine median oro-caecal transit times for the 2 liquid volumes; these times were 2.5 h for the 20-ml volume and 2.3 h for the 60-ml volume, which are about 1.5 h shorter than previously reported transit times in humans. An increase in volume administered did not significantly change either the t(50%) or oro-caecal transit time. The data also show that variability in both t(50%) and oro-caecal transit time within each monkey is not as great as the large variability between monkeys. Consequently, cynomolgus monkeys are good model animals to use for studies on the gastric emptying of drug-containing liquids after fasting; however, analysis of results from bioavailability studies must compensate for differences in the oro-caecal transit time between monkeys and humans.

Animals↗

PubMed2003

Effect of food on gastrointestinal transit of liquids in cynomolgus monkeys.

We investigated the gastrointestinal transit of liquids, as well as various gastric pH profiles, in fed cynomolgus monkeys. Twelve grams of a biscuit-type solid food were provided 1 h before the test. The acetaminophen method was used to determine the gastric half-emptying time (t(50%)), which provided an estimate of the gastric emptying rate. The gastric emptying rate of liquids was significantly reduced after food intake in monkeys. The mean t(50%) value was 143.5 min and comparable to that of humans after eating. However, there was a large variability in the t(50%) between individual animals as shown by the coefficient of variance of approximately 80%. Next, the median oro-caecal transit time in fed monkeys was determined to be 1.8 h, using the sulfasalazine-sulfapyridine method. There was no significant difference in oro-caecal transit time between unfed and fed monkeys; thus, food intake has no significant effect on the oro-caecal transit time of liquids in either monkeys or humans. However, the oro-caecal transit time in humans is about 2 h longer than that in monkeys. Our experiments using several different foods suggested that the typical human gastric pH profile could not be simulated in fed monkeys.

Acetaminophen↗

PubMed2003

Localized proton MRS of cerebral metabolite profiles in different mouse strains.

Localized proton MR spectroscopy (MRS) was used to quantify cerebral metabolite concentrations in NMRI (n = 8), BALB/c (n = 7), and C57BL/6 (n = 8) mice in vivo and 1 hr after global irreversible ischemia (2.35 T, STEAM, TR/TE/TM = 6000/20/10 ms, 4 x 3 x 4 mm(3) volume, corrections for cerebrospinal fluid). Anatomical MRI and proton MRS revealed significant differences of the C57BL/6 strain in comparison with both BALB/c and NMRI mice. While MRI volumetry yielded larger ventricular spaces of the C57BL/6 strain, proton MRS resulted in elevated concentrations of N-acetylaspartate (tNAA), creatine and phosphocreatine (tCr), choline-containing compounds (Cho), glucose (Glc), and lactate (Lac) relative to BALB/c mice and elevated Glc relative to NMRI mice. Apart from the expected decrease of Glc and increase of Lac 1 hr post mortem, C57BL/6 mice presented with significant reductions of tNAA, tCr, and Cho, whereas these metabolites remained unchanged in BALB/c and NMRI mice. The results support the hypothesis that the more pronounced vulnerability of C57BL/6 mice to brain ischemia is linked to strain-dependent differences of the cerebral energy metabolism.

Animals↗

PubMed2003

High mobility group A1 is expressed in metastatic adenocarcinoma to the liver and intrahepatic cholangiocarcinoma, but not in hepatocellular carcinoma: its potential use in the diagnosis of liver neoplasms.

BACKGROUND: An increased level of high mobility group A (HMGA) gene/protein expression has been demonstrated to be associated with many human neoplasms originating from a variety of tissues. However, HMGA1 expression has not yet been studied in hepatic tumors. In this study, we analyzed HMGA1 expression in hepatic primary and metastatic tumors in order to verify whether determination of the HMGA1 expression level could provide any diagnostic advantages in the pathological diagnosis of hepatic tumors. METHODS: Twenty samples of hepatocellular carcinoma, 5 samples of intrahepatic cholangiocarcinoma, and 21 samples of metastatic adenocarcinoma to the liver (15 metastatic tumors from colorectal carcinoma and 6 metastatic tumors from pancreatic carcinoma) were analyzed immunohistochemically using an HMGA1-specific antibody. RESULTS: While no significant nuclear immunoreactivity was found in hepatocytes of non-neoplastic liver tissue, 40% (2/5) of intrahepatic cholangiocarcinomas, 53.3% (8/15) of metastatic lesions from colorectal carcinoma, and 100% (6/6) of metastatic lesions from pancreatic carcinoma showed positive immunoreactivity. In contrast, all 20 samples of hepatocellular carcinoma were negative for HMGA1 nuclear immunoreactivity. Thus, hepatocellular carcinoma represents the first case of malignant neoplasia in which HMGA1 expression is not induced, which presents a striking contrast to several previous studies demonstrating the significance of increased HMGA gene/protein levels in carcinogenesis and/or tumor progression. CONCLUSIONS: Based on these findings, we conclude that the HMGA1 protein level could serve as a potential diagnostic marker that may enable the differential diagnosis between hepatocellular carcinoma and intrahepatic cholangiocarcinoma or metastatic adenocarcinoma to the liver.

Bile Duct Neoplasms↗

PubMed2003

Ceriporic acid C, a hexadecenylitaconate produced by a lignin-degrading fungus, Ceriporiopsis subvermispora.

A lignin-degrading basidiomycete, Ceriporiopsis subvermispora produces a series of alkyl- and alkenylitaconates (ceriporic acids). Previously, two alkylitaconic acids with tetradecyl and hexadecyl side chains were isolated and identified as 1-heptadecene-2,3-dicarboxylic acid (ceriporic acid A) and 1-nonadecene-2,3-dicarboxylic acid (ceriporic acid B). In the present study, one hexadecenylitaconate (ceriporic acid C) was isolated and its chemical structure was analyzed by glycolation and subsequent (1) trimethylsilation, or (2) acetalation with acetone and acetone-d6. Analyses of the isolated metabolite demonstrated that the hexadecenylitaconic acid was (Z)-1,10-nonadecadiene-2,3-dicarboxylic acid. The structure of the side chain in ceriporic acid C was the same as that of hexadecenylcitraconate, chaetomellic acid B. Thus, it was found that ceriporic acids share close structural similarity with alk(en)yl citraconate derivatives, chaetomellic acids and other lichen lactones, protolichesterinic, lichesterinic, and murolic acids.

Acetals↗

PubMed2003

Schwannoma of the spinal accessory nerve in the cisterna magna.

BACKGROUND: Intracranial schwannoma of the accessory nerve can be divided into two types. One is a jugular foramen type arising from the accessory nerve of the jugular foramen, while the other is an intracisternal type, which arises from the spinal root of the accessory nerve and is separate from the jugular foramen. The latter type is rare, and only 9 cases have been reported previously. CASE DESCRIPTION: A 46-year-old female presented with a large, midline mass lesion in the posterior fossa manifesting as foramen magnum syndrome. Magnetic resonance imaging (MRI) revealed a huge tumor with cystic lesion located in the cisterna magna with extension to the C1 spinal level. The tumor was totally removed by a suboccipital craniectomy and C1 laminectomy. It originated from the spinal root of the right accessory nerve. Temporary slight atrophy of the right sternocleidomastoid muscle was observed, but the patient was free of disease 2 years after treatment. CONCLUSIONS: We report a schwannoma of the spinal accessory nerve in the cisterna magna. The clinical and neuroradiological findings are discussed with a review of the literature. The initial symptoms were variable without loss of function of the cranial nerve, and the tumor tended to grow in the cisterna magna without laterality. Because of the absence of typical neurologic symptoms, early neuroradiological investigation by MRI is recommended for accurate diagnosis of these tumors.

Accessory Nerve Diseases↗

PubMed2003

Primary epithelioid hemangioendothelioma originating in the lower petroclival region: case report.

BACKGROUND: We report the first case of primary epithelioid hemangioendothelioma (EH) originating in the lower petroclival region. CASE DESCRIPTION: A 55-year-old female presented with a 45-year history of subclinical atrophy on the right side of her tongue and a 15-year history of hoarseness. Neuroimaging revealed an expansile, homogeneously enhanced intraosseous mass with bony shell and honeycomb configuration in the petroclival region. A right far lateral transcondylar approach was utilized for subtotal removal of the tumor, which demonstrated high vascularity in the petroclival bone. Histopathological and immunohistochemical examination confirmed the diagnosis of EH. Because of the intermediate malignancy, adjuvant gamma knife radiotherapy was performed for the residual mass 5 months after surgery. CONCLUSION: EH rarely occurs in the skull base region. The appearance of surrounding bony structure and rich vascularity are important findings for the differential diagnosis. A far lateral transcondylar approach provides sufficient exposure of the jugular tubercle and lower clivus. Additional radiotherapy may be recommended for residual tumors with a high MIB-1 labeling index.

Diagnosis, Differential↗

PubMed2003

Reliable and convenient method for the fixation of recording electrodes on nonshaved scalp for intraoperative electrophysiological monitoring: technical note.

BACKGROUND: Difficulties with the intraoperative monitoring of evoked responses sometimes occur because of displacement or dislodgment of the recording electrodes during surgery, especially if placed on nonshaved scalp. METHODS: An alternative fixation method of the recording electrode on the nonshaved scalp was developed. The sterile subdermal needle electrode was attached on the scalp by application of a transparent dressing (Tegaderm) over the electrode followed by fixing with a skin stapler. RESULTS: The needle electrodes were easily, quickly, and firmly positioned even on the nonshaved scalp. The responses of the intraoperative evoked potentials were highly stable and reproducible throughout the operation. CONCLUSION: This fixation method for subdermal needle electrodes on the scalp is safe, reliable, and convenient for intraoperative electrophysiological monitoring of evoked potentials, even if the scalp is not shaved.

Electrodes↗

PubMed2003

Purification and characterization of aspartate racemase from the bivalve mollusk Scapharca broughtonii.

High concentrations of D-aspartate occur in blood shell Scapharca broughtonii (Mollusca) tissues. We purified aspartate racemase from the foot muscle of the bivalve to electrophoretic homogeneity. The molecular mass shown by sodium dodecyl sulfate polyacrylamide gel was 39 kDa, while that shown by gel filtration ranged from 51 to 63 kDa. Pyridoxal 5'-phosphate-dependency of the enzyme was demonstrated by its absorption spectrum as well as the effects of amino-oxyacetate and other reagents on the activity and spectrum. The enzyme is highly specific to aspartate and does not racemize L-alanine, L-serine and L-glutamate. It showed the highest activity at pH 8 both in the conversion of L- to D- and D- to L-aspartate, and the optimal temperature was 25 degrees C. V(max) and K(m) values for L-aspartate were 7.39 micromolmin(-1)mg(-1) and 60.4 mM and those for D-aspartate were 22.6 micromolmin(-1)mg(-1) and 159 mM, respectively.

Amino Acid Isomerases↗

PubMed2003

Nucleotides modulate the activity of aspartate racemase of Scapharca broughtonii.

The activity of D-aspartate racemase purified from Scapharca broughtonii has been found to depend markedly on some nucleotides. Purine nucleoside monophosphates enhanced the enzyme activity, which was, on the contrary, lowered by purine nucleoside triphosphates and not affected by pyrimidine nucleotides. AMP produced the highest increase of seven-fold in the enzyme activity at 6 mM and a half-maximum increase at approximately 3.8 mM. ATP caused a half-maximum decrease in the activity at approximately 1.4 mM and the remaining activity was lower than 7% at saturating ATP concentrations. AMP and ATP both brought about changes in V(max) and not in K(m). Analysis of the effect of AMP and ATP suggests that each of them has its own primary binding site, which is different from the substrate-binding site. In view of these effects of the nucleotides, the roles of the racemase and D-aspartate in energy metabolism under anoxic conditions are discussed.

Adenosine Diphosphate↗

PubMed2003

Aspirin and indomethacin exhibit antiproliferative effects and induce apoptosis in T98G human glioblastoma cells.

The in vitro antiproliferative and apoptosis inducing properties of the nonsteroidal anti-inflammatory drugs (NSAIDs) like acetyl salicylic acid (aspirin) and indomethacin were investigated in T98G human glioblastoma cells to explore their potential role in the chemoprevention of human glioma. The biological effects induced by aspirin and indomethacin on T98G cells, in which the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were confirmed by RT-PCR and immunostaining, were investigated by studying cell proliferation and apoptosis assays. The antiproliferative effects occurred in a dose- and time-dependent manner on T98G cells by the treatment with 0.1 -2 mM aspirin and 25-100 microM indomethacin. Moreover, aspirin displayed the greatest growth inhibition within 24 h. Approximately 90% growth inhibition occurred following treatment either with 2 mM aspirin or 100 microM indomethacin by 72 h and induction of apoptosis was confirmed by DNA laddering and TUNEL assay. Our in vitro findings indicate that aspirin and indomethacin have an antiproliferative effect on T98G human glioblastoma cells at toxic concentrations.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Unusual growth of a left atrial myxoma complicated by a secundum atrial septal defect.

A 55 year-old man had a myxoma that originated in the left atrium and grew through a secundum atrial septal defect into the right atrium. The tumor, which was attached by a pedicle to the lateral wall of the left atrium near the right pulmonary vein, was resected under cardiopulmonary bypass. Transesophageal echocardiography was important in the successful outcome of surgical treatment.

Coronary Artery Bypass↗

PubMed2003

Construction of a homologous selectable marker gene for Lentinula edodes transformation.

We cloned a gene for the iron sulfur protein (Ip) subunit from an edible mushroom, Lentinula edodes, and introduced a point mutation that confers carboxin resistance into it. The mutant gene successfully transformed L. edodes with high efficiency (9 transformants/2.5 microg vector DNA). Restriction enzyme-mediated integration (REMI) increased the transformation efficiency by about two-fold.

Blotting, Southern↗

PubMed2003

Discordant twin: marked vascular communication between separated dichorionic diamniotic placentas.

We report on a woman who gave birth to dichorionic diamniotic twins with a birthweight discordancy of 30%. Her placenta exhibited characteristic features. The placental villous tissues were completely separated, but there was marked vascular communication between the two placentas. The lighter twin received less blood than the heavier twin via these vascular communications. Although the details are unknown, this abnormal placental structure may have caused the weight discordancy in this case. Clinicians must pay attention to placental vascular communication as one possible cause of twin discordancy in not only monochorionic but also dichorionic twins.

Adult↗

PubMed2003

Subependymal giant cell astrocytoma with positive tuberin expression--case report.

An 11-year-old male presented with subependymal giant cell astrocytoma (SEGA) without other manifestations of tuberous sclerosis such as facial angiofibroma, epilepsy, or mental retardation. The diagnosis was "possible tuberous sclerosis complex" (TSC). Total resection of the tumor was performed. Immunohistochemical study revealed positive tuberin expression. In general, loss of tuberin is thought to be critical to the TSC phenotype. Our case demonstrated clear expression of tuberin in the SEGA specimen.

Astrocytoma↗

PubMed2003

Facial neuropathy due to axonal degeneration and microvasculitis following gamma knife surgery for vestibular schwannoma: a histological analysis. Case report.

Complete facial palsy (House-Brackmann Grade VI) developed in a 63-year-old man with a vestibular schwannoma 25 months after he had undergone two gamma knife surgeries performed 33 months apart and involving a cumulative dose of 24 Gy directed to the tumor margin at the 50% isodose line. Magnetic resonance imaging demonstrated tumor enlargement with central nonenhancement, which initially had been recognized 21 months after the second radiosurgery. Microsurgery was performed to achieve total removal of the tumor. Histological and immunohistochemical examinations of the facial nerve specimen removed from the edge of the tumor revealed a loss of axons, proliferation of Schwann cells, and microvasculitis. In this case, microvasculitis and axonal degeneration were probably the major causes of the radiation-induced facial neuropathy.

Axons↗

PubMed2003

[A case of ruptured and unruptured developing cerebral aneurysms at the bilateral M2 bifurcations five years after surgery for ruptured aneurysm at the end of the azygos anterior cerebral artery].

A 36-year-old woman with 4 cerebral aneurysms at unusual sites including bilateral M2 bifurcation aneurysms is reported. She had been in good health in the previous 5 years since the treatment for a ruptured aneurysm at the end of the azygos anterior cerebral artery when she was 31 years old. Five years later, she became comatose with a huge hematoma in the right temporal lobe due to the rupture of the aneurysm at the right M2 bifurcation, which had been very small 5 years ago. She underwent an emergent clipping operation, and then she became alert with motor weakness extremities of on her left-side. Postoperative angiograms revealed a de novo aneurysm at the left M2 bifurcation and an aneurysm at the origin of the lenticulostriate artery, which has remained unchanged for 5 years. An aneurysm at the M2 bifurcation is rare, especially when it is situated bilaterally at the mirror sites. To detect de novo aneurysms, postoperative angiographical follow-up should be considered in patients with multiple aneurysms and in young patients.

Adult↗