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Biomedical subjects

M Shoji

Publications and source records attributed to M Shoji.

At least 55 records · Page 3Linked to original sources
PubMed2001

Nocturnal blood pressure dip in CADASIL.

The influence of a nocturnal blood pressure dip on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has not yet been clarified. We attempted to examine a correlation with the nocturnal blood pressure dip and CADASIL. We monitored circadian blood pressure patterns by the use of a portable blood pressure monitoring device in five patients with CADASIL and 10 age- and sex-matched control subjects. Based on nocturnal fall in mean arterial blood pressure (MABP), we classified patients into extreme dippers (nocturnal reduction of MABP > or =20%), dippers (> or =10% but <20%), nondippers (<10% but > or =0%), and inverted dippers (<0%). Three patients revealed non-dipper and two inverted dipper. Nighttime MABP fall was significantly lower in patients compared with control subjects (P<0.01). This study suggests that a lower nocturnal blood pressure fall may be partly associated with incidence and/or worsening of deep white matter lesions in CADASIL.

Brain↗
PubMed2001

HNF-1 regulates the liver-specific transcription of the chipmunk HP-20 gene.

The chipmunk hibernation-specific protein HP-20 is a component of the 140 kDa complex that drastically decreases in the blood during hibernation, and its gene is expressed specifically in the liver. To reveal molecular mechanisms underlying the liver-specific transcription of the HP-20 gene, we isolated chipmunk HP-20 genomic clones. The HP-20 gene spans approximately 6 kb, and consists of three exons. The transcription start site, as determined by 5' RACE-PCR analysis, was found to be 160 bp upstream of the translation initiation codon. Transient transfection studies in HepG2 cells revealed that the 57 bp 5' flanking sequence was sufficient for the liver-specific promoter activity. A database search revealed that this region contains a potential binding site for hepatocyte nuclear factor-1 (HNF-1). In a gel retardation assay, in vitro-synthesized HNF-1 bound to the 5' flanking sequence from -52 to -26. A similar shifted band was also observed with HepG2 nuclear extracts, and this complex was super-shifted by an anti-(HNF-1) Ig. When transfected into COS-7 cells, HNF-1 transactivated transcription from the HP-20 gene promoter, and this activity was abolished by a mutation of the HNF-1 binding site, indicating that HNF-1 plays an important role in HP-20 gene expression.

5' Flanking Region↗
PubMed2001

Early decrease of redox factor-1 in spinal motor neurons of presymptomatic transgenic mice with a mutant SOD1 gene.

Oxidative stress has been proposed to play a pivotal role in pathogenesis of both sporadic and familial amyotrophic lateral sclerosis (ALS). Expression of DNA repair enzyme redox factor-1 (Ref-1) protein was examined in the spinal cord of transgenic mice with an ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) gene. Immunoblotting and immunocytochemical analyses showed that the most spinal motor neurons lost the immunoreactivity for Ref-1 in the early presymptomatic stage that preceded significant loss of the neurons. The present result suggests that an early impairment of DNA repair in the spinal motor neurons may account for the mutant SOD1-mediated motor neuronal death in this model.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Chemical synthesis and biological evaluation of cis- and trans-12,13-cyclopropyl and 12,13-cyclobutyl epothilones and related pyridine side chain analogues.

The design, chemical synthesis, and biological evaluation of a series of cyclopropyl and cyclobutyl epothilone analogues (3-12, Figure 1) are described. The synthetic strategies toward these epothilones involved a Nozaki-Hiyama-Kishi coupling to form the C15-C16 carbon-carbon bond, an aldol reaction to construct the C6-C7 carbon-carbon bond, and a Yamaguchi macrolactonization to complete the required skeletal framework. Biological studies with the synthesized compounds led to the identification of epothilone analogues 3, 4, 7, 8, 9, and 11 as potent tubulin polymerization promoters and cytotoxic agents with (12R,13S,15S)-cyclopropyl 5-methylpyridine epothilone A (11) as the most powerful compound whose potencies (e.g. IC(50) = 0.6 nM against the 1A9 ovarian carcinoma cell line) approach those of epothilone B. These investigations led to a number of important structure-activity relationships, including the conclusion that neither the epoxide nor the stereochemistry at C12 are essential, while the stereochemistry at both C13 and C15 are crucial for biological activity. These studies also confirmed the importance of both the cyclopropyl and 5-methylpyridine moieties in conferring potent and potentially clinically useful biological properties to the epothilone scaffold.

Antineoplastic Agents↗
PubMed2001

Expressions of nitrotyrosine and TUNEL immunoreactivities in cultured rat spinal cord neurons after exposure to glutamate, nitric oxide, or peroxynitrite.

Although excitotoxic and oxidative stress play important roles in spinal neuron death, the exact mechanism is not fully understood. We examined cell damage of primary culture of 11-day-old rat spinal cord by addition of glutamate, nitric oxide (NO) or peroxynitrite (PN) with detection of nitrotyrosine (NT) or terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL). With addition of glutamate, NOC18 (a slow NO releaser) or PN, immunoreactivity for NT became stronger in the cytoplasm of large motor neurons in the ventral horn at 6 to 48 hr and positive in the axons of the ventral horn at 24 to 48 hr. TUNEL positive nuclei were found in spinal large motor neurons from 24 hr, and the positive cell number greatly increased at 48 hr in contrast to the vehicle. Pretreatment of cultures with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor antagonist, NO-suppressing agent, and antioxidant protected the immunoreactivity for NT or TUNEL. The present results suggest that both excitotoxic and oxidative stress play an important role in the upregulation of NT nitration and the apoptotic pathway in cultured rat spinal neurons.

Animals↗
PubMed2001

Impaired retrograde axonal transport of adenovirus-mediated E. coli LacZ gene in the mice carrying mutant SOD1 gene.

A replication-defective recombinant adenoviral vector containing E. coli lacZ gene was injected into the gastrocnemius muscles of transgenic mice carrying mutant Cu/Zn superoxide dismutase (SOD1) gene and non-transgenic wild-type mice at 40 weeks of age. After 60 and 90 h of the injection, lacZ staining was observed at the distal ends of the sciatic nerves in both mice groups, with the number and the distances greatly reduced in the transgenic mice. Mean velocities of retrograde transport for lacZ was estimated to be 2.1 and 0.05 mm/24 h in non-transgenic and transgenic mice, respectively. These results indicate that the retrograde axonal transport of foreign gene product is impaired in the mice model for familial amyotrophic lateral sclerosis.

Adenoviridae↗
PubMed2001

Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

Journal Article↗
PubMed2001

Abeta amyloidosis induces the initial stage of tau accumulation in APP(Sw) mice.

To clarify how Abeta deposits induce secondary tauopathy, the presence of phosphorylated tau, glycogen synthase kinase 3alpha (GSK3alpha), GSK3beta, cyclin-dependent kinase 5 (CDK5), mitogen-activated protein kinase (MAPK) and fyn were examined in the Tg2576 brain showing substantial brain Abeta amyloidosis and behavioral abnormalities. Phosphorylated tau at Ser199, Thr231/Ser235, Ser396 and Ser413 accumulated in the dystrophic neurites of senile plaques. The major kinase for tau phosphorylation was GSK3beta. Smaller contributions of GSK3alpha, CDK5 and MAPK were suggested. Thus, brain Abeta amyloidosis has a potential role in the induction of tauopathy leading to the mental disturbances of Alzheimer's disease.

Alzheimer Disease↗
PubMed2001

Diagnostic significance of tau protein in cerebrospinal fluid from patients with corticobasal degeneration or progressive supranuclear palsy.

Distinguishing corticobasal degeneration (CBD) from progressive supranuclear palsy (PSP) is clinically and pathologically difficult, and a useful biological marker to discriminative these two diseases has been a subject of clinical interest. In the present study, we assessed tau protein levels in cerebrospinal fluids by sandwich ELISA to distinguish CBD from PSP. The subjects consisted of 27 cases of CBD, 30 cases of PSP, and 36 healthy controls (CTL). The tau values in CBD were significantly higher than those in PSP (P<0.001) and those in CTL (P<0.001). The assay of CSF tau provided diagnostic sensitivity of 81.5% and specificity of 80.0% between CBD and PSP according to receiver-operating characteristic (ROC) curve analysis. When values were compared separately with respect to stage of the disease, differences in the values for moderate CBD vs. moderate PSP had the greatest significance (P<0.001 sensitivity 92.3%, specificity 100.0%), followed by cases of mild CBD and PSP (P<0.005, sensitivity 100.0%, specificity 87.5%). The values in severe CBD and PSP were not significantly different (P=0.07, sensitivity 100%, specificity 75.0%). Using data obtained from a larger number of disease cases, we confirmed our previous findings that tau protein levels in cerebrospinal fluids in patients with CBD are significantly higher than those in patients with PSP. Because tau protein levels in cerebrospinal fluids are significantly higher in early CBD cases than in early PSP cases, measurement of tau protein levels in cerberospinal fluids may be useful for the differential diagnosis of early CBD from early PSP.

Aged↗
PubMed2001

Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease.

The accumulation of amyloid beta protein (Abeta) in the Tg2576 mouse model of Alzheimer's disease (AD) was evaluated by ELISA, immunoblotting, and immunocytochemistry. Changes in Abeta begin at 6-7 months as SDS-insoluble forms of Abeta42 and Abeta40 that require formic acid for solubilization appear. From 6 to 10 months, these insoluble forms increase exponentially. As insoluble Abeta appears, SDS-soluble Abeta decreases slightly, suggesting that it may be converting to an insoluble form. Our data indicate that it is full-length unmodified Abeta that accumulates initially in Tg2576 brain. SDS-resistant Abeta oligomers and most Abeta species that are N-terminally truncated or modified develop only in older Tg2576 mice, in which they are present at levels far lower than in human AD brain. Between 6 and 10 months, when SDS-insoluble Abeta42 and Abeta40 are easily detected in every animal, histopathology is minimal because only isolated Abeta cores can be identified. By 12 months, diffuse plaques are evident. From 12 to 23 months, diffuse plaques, neuritic plaques with amyloid cores, and biochemically extracted Abeta42 and Abeta40 increase to levels like those observed in AD brains. Coincident with the marked deposition of Abeta in brain, there is a decrease in CSF Abeta and a substantial, highly significant decrease in plasma Abeta. If a similar decline occurs in human plasma, it is possible that measurement of plasma Abeta may be useful as a premorbid biomarker for AD.

Aging↗
PubMed2001

Brain Abeta amyloidosis in APPsw mice induces accumulation of presenilin-1 and tau.

APPsw transgenic mice (Tg2576) overproducing mutant amyloid beta protein precursor (betaAPP) show substantial brain Abeta amyloidosis and behavioural abnormalities. To clarify the subsequent abnormalities, the disappearance of neurons and synapses and dystrophic neurite formation with accumulated proteins including hyperphosphorylated tau were examined. Tg2576 demonstrated substantial giant core plaques and diffuse plaques. The number of neurons was significantly decreased in the areas containing the amyloid cores compared with all other areas and corresponding areas in non-transgenic littermates in sections visualized by Nissl plus Congo red double staining (p<0.001). The presynaptic protein alpha-synuclein and postsynaptic protein drebrin were also absent in the amyloid cores. betaAPP and presenilin-1 were accumulated in dystrophic neurites in and around the core plaques. Tau phosphorylated at five independent sites was detected in the dystrophic neurites in the amyloid cores. Thus, the giant core plaques replaced normal brain tissues and were associated with subsequent pathological features such as dystrophic neurites and the appearance of hyperphosphorylated tau. These findings suggest a potential role for brain Abeta amyloidosis in the induction of secondary pathological steps leading to mental disturbance in Alzheimer's disease.

Alzheimer Disease↗
PubMed2001

The role of the hemostatic system in tumor growth, metastasis, and angiogenesis: tissue factor is a bifunctional molecule capable of inducing both fibrin deposition and angiogenesis in cancer.

Cancer patients are prone to venous thromboembolism (VTE), and this hypercoagulability favors tumor growth and metastasis. After a brief review of the clinical aspects of VTE and cancer, we discuss the pathogenesis of hypercoagulability with an emphasis on the role of tissue factor (TF). The discovery that, in addition to tumor cells, TF is expressed by tumor-associated macrophages and tumor-associated endothelial cells led to studies of the role of TF in the regulation of tumor angiogenesis. In human lung cancer, melanoma, and breast cancer, TF and vascular endothelial growth factor (VEGF) co-localize in tumor cells; a close correlation exists between TF and VEGF synthesis (P = .001) in tumor cell lines and with angiogenesis in vivo in a severe, combined immunodeficient mouse model. Transfection of a TF/VEGF low-producing human tumor cell line with full length TF complementary DNA (cDNA) results in conversion to a high producer of TF and VEGF; transfection of a deletion-mutant TF cDNA lacking cytoplasmic serine residues restores full TF procoagulant activity but not VEGF synthesis to the cells. These results suggest that the cytoplasmic tail of TF is necessary for tumor cell VEGF synthesis. Targeting of TF in tumors and tumor-associated blood vessels is discussed as a strategy for drug delivery and rational anti-cancer and anti-angiogenesis drug design.

Cell Division↗
PubMed2001

Spontaneous necrosis of gallbladder carcinoma in patient with pancreaticobiliary maljunction.

While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma.

Adenocarcinoma, Papillary↗
PubMed2001

Psoas abscess and cellulitis of the right gluteal region resulting from carcinoma of the cecum.

Although retroperitoneal or psoas abscess is an unusual clinical problem, the insidious and occult characteristics of this abscess sometimes cause diagnostic delays, resulting in considerably high morbidity and mortality. In particular, psoas abscess caused by perforated colon carcinoma is uncommon. We report a case of psoas abscess caused by a carcinoma of the cecum. A 72-year-old Japanese woman was admitted to our hospital, with pain in the right groin and buttock. The pain had appeared 6 months before admission, and the symptoms had then been relieved by oral antibiotics. On March 25, 1999, inflammatory signs in the right buttock indicated localized cellulitis, and incision and drainage was performed at a local hospital. The patient was referred to our hospital on the same day. On admission to our hospital, computed tomography (CT) scan revealed a thick right-sided colonic wall and enlargement of the right ileopsoas muscle. Barium enema and colonofiberscopy revealed an ulcerated tumor occupying the entire circumference of the cecum. A retroperitoneal abscess and fistula had been formed by the retroperitoneal perforation of cecum carcinoma: surgical resection was performed after remission of the local inflammatory signs. Operative findings indicated that the cancerous lesion and its surrounding tissues were firmly attached to the right iliopsoas and major psoas muscle, and en-bloc resection, including adjacent muscular tissue, was performed. The fact that carcinoma of the colon could be a cause of psoas abscess and cellulitis in the gluteal region should be considered when an unexplained psoas abscess is diagnosed.

Adenocarcinoma↗
PubMed2001

Pancreatic ductal adenocarcinoma associated with Potter type III cystic disease.

Although polycystic liver disease (PLD) is known to be associated with autosomal dominant polycystic kidney disease, a finding of PLD with pancreatic ductal adenocarcinoma is extremely rare. We have experienced one such case of a ductal adenocarcinoma of the pancreas in a patient with Potter type III cystic disease of the liver and kidney. A 63-year-old man was admitted to our hospital because of obstructive jaundice. Six months previously, on admission to a local hospital for treatment of diabetes mellitus, he had been found to have polycystic disease of the liver and kidney. Ultrasound examination revealed dilatation of the intrahepatic bile duct and the common bile duct. Blood tests showed an elevated total bilirubin level. Abdominal computed tomography scans and magnetic resonance imaging demonstrated polycystic lesions in the liver and the bilateral kidneys. Percutaneous transhepatic cholangio-drainage was performed, and fluorography of the biliary tree revealed obstruction of the lower common bile duct, causing jaundice. This appears to be a case of independent association of pancreatic ductal adenocarcinoma with polycystic disease of the liver and kidney. The patient's sister, who also had polycystic disease of the liver and kidney, had died of squamous cell carcinoma of the tongue. Although familial associations of carcinomas with polycystic liver disease may be extremely rare, they provide a perspective for the etiology of polycystic liver disease.

Abnormalities, Multiple↗
PubMed2001

The Alzheimer-related gene presenilin-1 facilitates sonic hedgehog expression in Xenopus primary neurogenesis.

We analyzed the influence of presenilins on the genetic cascades that control neuronal differentiation in Xenopus embryos. Resembling sonic hedgehog (shh) overexpression, presenilin mRNA injection reduced the number of N-tubulin+ primary neurons and modulated Gli3 and Zic2 according to their roles in activating and repressing primary neurogenesis, respectively. Presenilin increased shh expression within its normal domain, mainly in the floor plate, whereas an antisense X-presenilin-alpha morpholino oligonucleotide reduced shh expression. Both shh and presenilin promoted cell proliferation and apoptosis, but the effects of shh were widely distributed, while those resulting from presenilin injection coincided with the range of shh signaling. We suggest that presenilin may modulate primary neurogenesis, proliferation, and apoptosis in the neural plate, through the enhancement of shh signaling.

Amyloid Precursor Protein Secretases↗
PubMed2001

A convenient method for discriminating between natural and depleted uranium by gamma-ray spectrometry.

A convenient method for discriminating between natural and depleted uranium reagent was developed by measuring and analyzing the gamma-ray spectra of some reagents with no standard source. The counting rates (R) of photoelectric peaks of gamma-rays from nuclides with the same radioactivity divided by their emission probability (B) are expressed as a function of gamma-ray energy. The radioactivities of 234Th and 234mPa and 21.72 times that of 235U are equal to the radioactivity of 235U in natural uranium. Therefore, the plot of 21.72-fold R/B for 235U should be on a curve fitted to the points for 234Th and 234mPa in natural uranium. Depleted uranium with a 235U isotopic composition of less than 0.68% could be discriminated from natural uranium in the case of a reagent containing 4.0 g of uranium.

Algorithms↗