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H Sugimoto

Publications and source records attributed to H Sugimoto.

At least 37 records · Page 2Linked to original sources
PubMed2001

Rapid and simultaneous determination of mycophenolic acid and its glucuronide conjugate in human plasma by ion-pair reversed-phase high-performance liquid chromatography using isocratic elution.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of mycophenolic acid (MPA) and its glucuronide conjugate (MPAG) in human plasma. The method involves protein precipitation with acetonitrile, followed by ion-pair reversed-phase chromatography on C18 column, with a 40 mM tetrabutyl ammonium bromide (TBA)-acetonitrile (65:35, v/v) mobile phase. A 20-microl volume of clear supernatant was injected after centrifugation, and the eluent was monitored at 304 nm. No interference was found either with endogenous substances or with many concurrently used drugs, indicating a good selectivity for the procedure. Calibration curves were linear over a concentration range of 0.5-20.0 microg/ml for MPA and 5-200 microg/ml for MPAG. The accuracy of the method is good, that is, the relative error is below 5%. The intra- and inter-day reproducibility of the analytical method is adequate with relative statistical deviations of 6% or below. The limits of quantification for MPA and MPAG were lower than 0.5 and 5.0 microg/ml, respectively, using 50 microl of plasma. The method was used to determine the pharmacokinetic parameters of MPA and MPAG following oral administration in a patient with renal transplantation.

Calibration↗
PubMed2001

Semaphorin 4C, a transmembrane semaphorin, [corrected] associates with a neurite-outgrowth-related protein, SFAP75.

Semaphorin 4C (S4C, previously called M-SemaF) was recently identified as a brain rich transmembrane member of semaphorin family of the vertebrate. In the cytoplasmic domain of S4C there is a proline-rich region suggesting that the cytoplasmic domain may play an important role in Sema4C function. In this study, we have identified the cytoplasmic domain (cd) of M-SemaF(S4C)-associating protein with a Mr of 75 kDa, named SFAP75, from mouse brain. SFAP75 turned out to be the same as the recently reported neurite-outgrowth-related protein named Norbin. Deletion mutants analyses of S4C and SFAP75 revealed that the membrane-proximal region of S4Ccd binds to the intermediate region of SFAP75. Western blot and immunohistochemical analyses with anti-Sema4C and anti-SFAP75 antibodies indicated that S4C and SFAP75 were specially enriched in the brain with a similar distribution pattern to each other. These results suggest that S4C interacts with SFAP75 and plays a role in neural function in brain.

Animals↗
PubMed2001

Identification of transcriptional enhancer factor-4 as a transcriptional modulator of CTP:phosphocholine cytidylyltransferase alpha.

CTP:phosphocholine cytidylyltransferase (CCT) is the rate-limiting and regulated enzyme of mammalian phosphatidylcholine biosynthesis. There are three isoforms, CCTalpha, CCTbeta1, and CCTbeta2. The mouse CCTalpha gene promoter is regulated by an enhancer element (Eb) located between -103 and -82 base pairs (5'-GTTTTCAGGAATGCGGAGGTGG-3') upstream from the transcriptional start site (Bakovic, M., Waite, K., Tang, W., Tabas, I., and Vance, D. E. (1999) Biochim. Biophys. Acta 1436, 147-165). To identify the Eb-binding protein(s), we screened a mouse embryo cDNA library by the yeast one-hybrid system and obtained 19 positive clones. Ten cDNA clones were identified as transcriptional enhancer factor-4 (TEF-4). The TEF-binding consensus sequence, 5'-(A/T)(A/G)(A/G)(A/T)ATG(C/T)(G/A)-3', was identified within the Eb binding region. Gel-shift analysis using radiolabeled Eb fragment as a probe showed that cell extracts from yeast expressing hemagglutinin-tagged TEF-4 caused a marked band retardation that could be prevented with an anti-hemagglutinin antibody. When COS-7 cells were transfected with TEF-4, CCTalpha promoter-luciferase reporter activity and CCTalpha mRNA levels increased. A TEF-4 deletion mutant containing a DNA-binding domain, mTEA(+), stimulated the CCTalpha promoter activity, whereas protein lacking the DNA binding domain, mTEA(-), did not. Unexpectedly, when the ATG core of the TEF-4 binding consensus within the Eb region was mutated, promoter activity was enhanced rather than decreased. Thus, TEF-4 might act as a dual transcriptional modulator as follows: as a suppressor via its direct binding to the Eb element and as an activator via its interactions with the basal transcriptional machinery. These results provide the first evidence that TEF-4 is an important regulator of CCTalpha gene expression.

3T3 Cells↗
PubMed2001

Donepezil hydrochloride: a treatment drug for Alzheimer's disease.

The role of the cholinergic system with respect to cognitive deficits characteristic of Alzheimer's disease (AD) has led to a number of studies focusing on the development of acetylcholinesterase (AChE) inhibitors as a drug for treating this disease. The earliest known AChE inhibitors, namely, physostigmine and tacrine, performed poorly in clinical trials (e.g., poor oral activity, brain penetration, and hepatotoxic liability). Studies were then focused on finding a new type of acetylcholinesterase inhibitor that would overcome the disadvantages of these two compounds. Donepezil hydrochloride inaugurates a new class of AChE inhibitors with longer and more selective action and with manageable adverse effects.

Alzheimer Disease↗
PubMed2001

Paravertebral neurinoma associated with aggressive intravertebral extension.

Neurinomas are relatively common benign tumors thought to arise from nerve sheath cells. Although intraosseous neurinomas may destroy the bone, extraosseous neurinomas with extensive destruction and invasion of bone are considered rare. We present two unusual cases of a benign extraosseous neurinoma that extensively invaded the vertebral body through the nutrient canal.

Adult↗
PubMed2001

Reversal of portal flow after acute rejection in living-donor liver transplantation.

Portal hepatofugal flow is rare after liver transplantation. We experienced a case in which hepatofugal portal flow was observed in acute rejection. A 6-year-old boy with glycogen storage disease type Ia underwent living-donor liver transplantation. On postoperative day 7, portal venous peak velocity was markedly decreased without portal thrombosis and obstruction of the hepatic vein, and hepatic arterial peak velocity increased reciprocally. Based on a diagnosis of acute rejection, made on postoperative day 8, we initiated steroid pulse therapy. Despite the employment of this therapy, continuous hepatofugal portal flow was observed in the entire liver on postoperative day 8. On day 12, as the liver disorder progressed, the Doppler waveform in the portal vein changed from continuous to pulsatile hepatofugal flow. The patient died of liver failure on day 14. The histological findings of a biopsy specimen on day 9 showed centrilobular necrosis, while total hepatocellular necrosis was seen at autopsy. Hepatofugal flow after liver transplantation is considered to be an ominous sign caused by several factors, and its appearance indicates a fatal condition.

Child↗
PubMed2001

Delayed rupture of a pseudoaneurysm following pancreatoduodenectomy: report of a case.

We report herein the case of a 63-year-old man in whom delayed rupture of a pseudoaneurysm occurred 120 days following pancreatoduodenectomy. Color Doppler examination indicated a pseudoaneurysm originating from the ligated gastroduodenal artery. Transcatheter arterial embolization was done at the common hepatic artery, proximal and distal to the pseudoaneurysm, with microcoils. The patient had a minor elevation of liver enzymes, which subsequently returned to normal. Due to the absence of any postoperative complications such as pancreatic anastomotic leakage, we assumed that the pseudoaneurysm formation had been caused by a weakness in the arterial wall according to skeletonization resulting from lymphadenectomy and intraoperative radiation therapy. To our knowledge, this case represents the longest interval between pancreatoduodenectomy and rupture of a pseudoaneurysm ever to be reported in the literature.

Aneurysm, False↗
PubMed2001

A single amino acid change at Leu-188 in the reverse transcriptase of HIV-2 and SIV renders them sensitive to non-nucleoside reverse transcriptase inhibitors.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are selective for human immunodeficiency virus type 1 (HIV-1) and generally not effective on HIV-2 or simian immunodeficiency virus (SIV). Only SIVagm was found to be sensitive to NNRTIs. When the amino acid differences in RT between SIVmac and SIVagm were compared with the known amino acid substitutions of NNRTI-resistance variants of HIV-1, we came to consider that the amino acid residue Leu-188 of HIV-2 and SIVmac might be related to their resistance to NNRTIs. To test this hypothesis, we substituted Leu-188 to Cys or Tyr in HIV-2 and SIVmac, and examined sensitivity of the mutant molecular clones to NNRTIs. The L188Y mutant of HIV-2 became completely sensitive to delavirdine and efavirenz, while that of SIVmac was also significantly sensitive to these NNRTIs. We further isolated NNRTI-resistant variants from these mutant viruses and determined amino acid substitutions in RT. The roles of the observed substitutions in NNRTI-resistance were further confirmed by site-directed mutagenesis. Our study reveals the crucial role of L188 in the natural resistance of HIV-2 and SIVmac to NNRTIs. Furthermore, the observed substitutions in RT of HIV-2 and SIVmac support the common mechanism of action of NNRTIs against HIV-1, HIV-2 and SIV.

Alkynes↗
PubMed2001

The role of Gd-enhanced three-dimensional MRI fast low-angle shot (FLASH) in the evaluation of symptomatic lumbosacral nerve roots.

In the field of lumbar spine disorders, three-dimensional (3-D) magnetic resonance imaging (MRI) can clearly depict a lumbar nerve root from the distal region to the dorsal root ganglion. In this study, we used a gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced-three-dimensional (3-D) fast low-angle shot (FLASH) sequence when examining lumbosacral disorders. The subjects were 33 patients (14 men and 19 women) in whom lumbosacral neural compression had been diagnosed clinically. Twenty-one patients had lumbar disc herniation, 11 had lumbar spinal stenosis, and 1 had lumbar radiculopathy caused by rheumatoid arthritis. Five subjects with low back pain were also studied as a control group. In all patients and in all 5 of the controls, the dorsal root ganglion of every root was enhanced clearly. There was no root enhancement in the 5 controls. Enhancement of the symptomatic nerve roots, caused by compression, was found in 11 of the 33 patients. All 11 patients had radiculopathy, and muscle weakness was more frequent in patients with enhanced nerve roots than in those without enhancement. There was no enhancement of the cauda equina, even in the patients with cauda syndrome. The enhancement effect may reflect some pathological condition of the compressed nerve root and needs to be studied further.

Adolescent↗
PubMed2001

Nitric oxide system is involved in glomerular hyperfiltration in Japanese normo- and micro-albuminuric patients with type 2 diabetes.

Glomerular hyperfiltration plays a pathogenic role in the early stages of diabetic nephropathy. Experimental studies in laboratory animals suggest that nitric oxide (NO) might be involved in the pathogenesis of glomerular hyperfiltration. We performed a cross-sectional study to determine the relationship between diabetic glomerular hyperfiltration and the NO system. Normoalbuminuric (n=41), microalbuminuric (n=25), and macroalbuminuric (n=16) patients with type 2 diabetes were recruited in this study and compared with age-matched 84 non-diabetic control subjects. Creatinine clearance and urinary NO(2)(-)/NO(3)(-) excretion (urinary NOx) were measured, and the expression of endothelial cell nitric oxide synthase (ecNOS) was evaluated in human renal tissues. Glomerular hyperfiltration was present in 19 (37.5%) and nine (36.6%) of normoalbuminuric and microalbuminuric type 2 diabetic patients, respectively. The urinary NOx was significantly higher in normoalbuminuric patients compared with normal subjects. Creatinine clearance correlated significantly with urinary NOx in normoalbuminuric and microalbuminuric patients. Immunohistochemical staining intensities for ecNOS were significantly increased in glomerular endothelial cells of microalbuminuric type 2 diabetic patients as compared with the control subjects. These results suggest that NO may contribute to the pathogenesis of glomerular hyperfiltration in Japanese type 2 diabetic patients.

Adult↗
PubMed2001

Telemedical support using real-time ultrasonography and endoscopy images.

We developed a telecommunications apparatus (TMS-6101, NIHON KOHDEN WELLNESS CORPORATION, Tokyo, Japan) and evaluated its clinical utility as a telemedical support system. It is capable of transmitting on a real-time basis such vital signs as blood pressure, arterial O2 saturation and ECG recordings, which are measured at bedside using the Life-Mate monitor (NIHON KOHDEN WELLNESS Co.). It is also capable of transmitting moving video-camera pictures in real time. In this study we assessed its application for telemedical supports with particular emphasis on ultrasonography and endoscopy images since reports of such applications are lacking. Employing this system, several kinds of technically demanding endoscopic procedures were supported successfully under the supervision of at least one off-site specialist physician. The system proved to be a very useful medical resource, since it facilitated high quality medical care and specialist consultation at any location without those specialists traveling to the scene.

Endoscopy↗
PubMed2001

Rapid and simple determination of mycophenolic acid in human plasma by ion-pair RP-LC with fluorescence detection.

Mycophenolic acid (MPA) is an immunosuppressive drug given as the prodrug of mycophenolate mofetil (MMF). In order to investigate the pharmacokinetics of MPA, a simple, specific, sensitive and reliable method has been established for the quantitative determination of MPA in plasma from renal transplant recipients. The method involves a single-step protein precipitation procedure and a specific determination by ion-pair reversed-phase high-performance liquid chromatography (HPLC) with fluorescence detection. Separation was achieved on a C18 column (150 x 4.6 mm, 5 microm) with a mobile phase composed of borate buffer (pH 10.0; 50 mM)--acetonitrile--tetrabutylammonium bromide (200 mM) (75:25:1, v/v/v). The fluorescence detector was set at 310 (excitation) and 430 nm (emission). Following protein precipitation with ice-cold acetonitrile, clear supernatants (50 microl) were injected into the HPLC system. The retention time of MPA was approximately 4.5 min. The HPLC run time was 8 min. The assay was linear in concentration range 0.2-20.0 microg/ml for MPA in human plasma. Precision of the assay in the concentration range examined was from 0.89 to 3.21% for the intra-assay run and from 3.01 to 4.35% for the inter-assay run. A limit of detection was 0.05 microg/ml at a signal-to-noise ratio of 3. This validated method was then applied to the determination of MPA concentrations in renal transplant recipients after oral administration of 0.75 g of MMF.

Chromatography, High Pressure Liquid↗
PubMed2001

Bupivacaine hydrochloride induces muscle fiber necrosis and hydroxyl radical formation-dimethyl sulphoxide reduces hydroxyl radical formation.

We induced acute skeletal muscle necrosis in rats using bupivacaine hydrochloride and found that both 2,5- and 2,3-dihydroxybenzoic acid significantly increased in skeletal muscle. A single administration of dimethyl sulphoxide, a free radical scavenger, significantly lowered concentrations of 2,5- and 2,3-dihydroxybenzoic acid. These results suggest that dimethyl sulphoxide is an effective hydroxyl radical scavenger and may be useful in the treatment of myopathy.

Anesthetics, Local↗
PubMed2001

Pustulotic arthro-osteitis: defining the radiologic spectrum of the disease.

Pustulotic arthro-osteitis (PAO) was termed by Sonozaki et al., who discussed the relationship between palmoplantar pustulosis (PPP) and osteoarticular inflammation. Manifestations of PAO are observed in the anterior chest wall, the spine, the pelvis, the sacroiliac joint, and the long bones. Hyperostosis is a radiological feature of PAO; furthermore, anterior chest wall involvement is common. The term SAPHO syndrome (SAPHO being an acronym for synovitis, acne, pustulosis, hypertostosis, and osteitis) has been coined to describe disease that manifests sterile inflammatory bone lesions together with skin eruptions. SAPHO syndrome groups together the following osteo-articular lesions that have been described as separate medical entities: chronic recurrent multifocal osteomyelitis (CRMO), PAO, and arthro-osteitis associated with a follicular occlusive triad. Osseous changes due to psoriasis vulgaris and generalized pustular psoriasis can be radiologically and clinically distinguishable from osseous changes due to PPP, acne, and CRMO as seronegative spondyloarthropathies.

Acquired Hyperostosis Syndrome↗
PubMed2001

MR imaging for evaluation of early rheumatoid arthritis.

In rheumatoid arthritis (RA), due to its superior contrast resolution and tomographic nature, magnetic resonance (MR) imaging can depict soft tissue and joint involvement better than plain radiography. Active synovitis and pannus are shown by a wide variety of contrast on T1- and T2-weighted images. They are markedly enhanced by intravenous gadolinium-chelate injection. Fat-suppressed T1-weighted imaging with gadolinium enhancement is the most sensitive technique to demonstrate these tissues. Compared with plain radiography, MR imaging is more sensitive and equally specific in the diagnosis of early RA compared with plain radiography. MR imaging is useful in the diagnosis and treatment of patients who are suspected of having early RA.

Adult↗
PubMed2001

Intraoperative ultrasonography by high-resolution annular array transducer for intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: Intraductal papillary mucinous tumors of the pancreas (IPMT) spread along the main pancreatic duct (MPD) or branch duct, or both. It is important to intraoperatively determine the extent of IPMT lesions in the MPD to perform a successful operation. METHODS: This study included 27 consecutive patients with IPMT who were referred for operation and who had undergone endoscopic ultrasonography, endoscopic retrograde pancreatography, and computed tomography as a diagnostic examination. Intraoperative ultrasonography with a 7.5-MHz annular array transducer and a 7. 5-MHz conventional transducer was performed. All patients underwent operation, and the pathology was confirmed. Endoscopic ultrasonography, endoscopic retrograde pancreatography, intraoperative conventional ultrasonography, and intraoperative annular array ultrasonography results were correlated with those from a pathologic examination of the resected specimens. The diagnostic accuracy of these 4 modalities in the detection of IPMT lesions in the MPD and the branch duct was confirmed. RESULTS: The diagnostic criterion of IPMT lesions by intraoperative annular array ultrasonography was the presence of echogenic masses with irregular margins in the MPD or branch duct, or both. An IPMT lesion in the MPD was found in 22 of the 27 patients. Intraoperative annular array ultrasonography detected 5 cases of IPMT lesions in the MPD that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. In 3 of 5 patients, pancreatic resection was extended to remove IPMT lesions. Intraoperative annular array ultrasonography detected 3 multifocal lesions that could not be detected by preoperative examinations. For the diagnosis of IPMT lesions in the MPD, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 86%, 100%, and 89%; the respective values were 50%, 100%, and 59% for endoscopic retrograde pancreatography; 59%, 100%, and 67% for endoscopic ultrasonography, and 32%, 100%, and 44% for intraoperative conventional ultrasonography. For the diagnosis of IPMT lesions in the branch duct, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 95%, 100%, and 96%. CONCLUSIONS: Intraoperative annular array ultrasonography is suitable for longitudinal scanning of the MPD, useful for accurate diagnosis of the extent of IPMT in the pancreas, and valuable for planning surgical strategy and successful operations for IPMT.

Adenocarcinoma, Mucinous↗
PubMed2001

Delayed hemispheric neuronal loss in severely head-injured patients.

Recent experimental studies have revealed that traumatic brain injury as well as ischemic brain injury can cause chronic progressive neuronal damage. In the present study, we demonstrate previously unreported delayed cerebral atrophy on computerized tomography (CT) scans in severely head-injured patients. Seventeen severely head-injured patients who required mild hypothermia to control intracranial hypertension after the failure of conventional therapies were retrospectively analyzed. All 17 patients survived more than 1 year. Delayed neuronal loss (DNL) was observed in only eight of the 17 patients. Eight patients with DNL required longer durations of mild hypothermia to control intracranial hypertension than nine patients without DNL. Six of these eight patients with DNL achieved functional recovery despite progressive atrophic changes demonstrated on CT scans. On CT scans, DNL was characterized by (1) the sudden appearance at several months postinjury of a low-density area in the hemisphere ipsilateral to the injury; (2) the preservation of essential cortical structure although related white matter structures showed severe atrophic changes; and (3) no spread of the low-density area to the contiguous territory of the other main cerebral artery. It is concluded that focal primary injury to underlying brain, if severe enough, can result in delayed hemispheric atrophy.

Adolescent↗