Search PubMed⌕ Search

Biomedical subjects

H Mori

Publications and source records attributed to H Mori.

At least 217 records · Page 12Linked to original sources

International telemicroscopy with a 3 MV ultrahigh voltage electron microscope.

The ability for remote microscope operation via a network connection was added recently to the ultrahigh voltage electron microscope (UHVEM) in Osaka University, and used successfully for the observation of thick biological samples across the Pacific Ocean by researchers at the National Center for Microscopy and Imaging Research (NCMIR) at the University of California San Diego. High-quality images at video rate were transferred by a satellite link and control signals were transmitted by an ISDN connecting the workstations at both sites. Most microscope functions operated from the console of the UHVEM were replicated on the graphical user interface of the remote workstation. By clicking on icons or in boxes in the display window with a mouse, the researcher could operate the UHVEM from the remote-site. The total delay time for sending images and returning control signals was about 0.7 s, which did not interfere significantly with the smooth operation of the instrument. Researchers at the remote site were able to record images on film in the microscope which were later sent to San Diego.

Animals↗

Characterization of nociceptin/orphanin FQ-induced pain responses in conscious mice: neonatal capsaicin treatment and N-methyl-D-aspartate receptor GluRepsilon subunit knockout mice.

Activation of primary afferent C fibers gives rise to spinal release of substance P and glutamate, and these mediators facilitate the cascade of nociceptive processing. We recently showed that intrathecal administration of nociceptin or orphanin FQ (hereafter called nociceptin) induced hyperalgesia to noxious thermal stimuli and allodynia to innocuous tactile stimuli applied to conscious mice. In the present study, we designed experiments to elucidate the pathways and mediators of nociceptin-evoked pain responses. Neonatal capsaicin treatment eliminated the induction of hyperalgesia and allodynia by nociceptin. Whereas this treatment markedly reduced the content of substance P in the spinal cord, it did not affect the nociceptin content or the expression of nociceptin receptors and GluRvarepsilon and GluRzeta subunits of N-methyl-D-aspartate receptors in it. The substance P antagonists CP96,345 and CP99,994 blocked the nociceptin-induced hyperalgesia, but not the allodynia. In contrast, the nociceptin-evoked allodynia, but not hyperalgesia, disappeared in N-methyl-D-aspartate receptor GluRvarepsilon1 subunit knockout mice. Both nociceptin-evoked hyperalgesia and allodynia were attenuated by morphine in a dose-dependent manner. Taken together, these results demonstrate that capsaicin-sensitive primary afferent fibers are involved not only in thermal hyperalgesia but also in tactile allodynia induced by nociceptin, but in different pathways; the former is mediated by substance P and the latter is mediated by glutamate through the N-methyl-D-aspartate receptor comprising the GluRvarepsilon1 subunit.

Analgesics, Opioid↗

Superparamagnetic iron oxide-enhanced MR imaging for early and late radiation-induced hepatic injuries.

Superparamagnetic iron oxide (SPIO)-enhanced MRI was performed in twenty-one patients undergoing proton-beam radiotherapy for hepatocellular carcinomas. Patients were divided into two groups: early and late phase hepatic injuries. Each group was investigated 3 to 9 weeks and 4 to 65 months after the start of irradiation, respectively. T(1)-weighted, T(2)-weighted, and T(2)*-weighted images were obtained before and after SPIO administration. In all postcontrast sequences in the early phase, irradiated livers demonstrated relatively higher intensity than nonirradiated livers and the radiation-to-liver contrast-to-noise ratio (C/N) was improved. Postcontrast T(2)*-weighted images showed the highest C/N. In the late phase, the irradiated areas showed high intensity on T(2)-weighted images and low intensity on T(1)-weighted images without SPIO, while high intensity on T(1)-weighted images with SPIO. The C/N increased with SPIO in all sequences and postcontrast T(2)-weighted images showed the highest C/N in the late phase. SPIO-enhanced MRI is useful to evaluate this entity both in the early and late phase of clinical studies.

Aged↗

Functional genomics of Escherichia coli in Japan.

Completion of the genome sequence of the model bacterium Escherichia coli has produced nearly 2000 open reading frames (ORFs) that remain to be functionally characterized. To accomplish this goal, we have organized a working project team in Japan and have begun construction of clones containing each of the putative ORFs. The procedure has been conceived such that we shall be able to perform systematic analysis of the shut-off as well as forced expression in vivo of each ORF and purification of its protein product for further biochemical studies. In addition, we have started a collection of various genetic and biochemical data of E. coli published in the past, and analyses of the data from a bio-informatics point of view. Thus, we aim at reaching complete understanding of this model organism in the near future.

Bacterial Proteins↗

Development of a new type nozzle and spray-drier for industrial production of fine powders.

Sophisticated nozzle and spray-drier were newly developed. The nozzle type was that of four-phase spraying, where two liquid streams and two air streams were blown off. The spray pattern from the nozzle was of a hollow-cone type. Mean diameter of droplets in the mist was 13.2 microm in weight average in the condition of blowing at 776 g/min in air flow and 500 ml/min in liquid flow. That is, the weight-based flow ratio of air to liquid was as small as 1. 55. The geometric standard deviation of the droplet size was less than 1.65. This nozzle was still available for a concentrated suspension up to 27% solid without formation of the sludge on the orifice. Thus, fine powder with 1.99 microm in mean diameter was obtained by means of the nozzle and the spray-drier newly developed by us. These are promising for industrial production of the fine powder with low energy and high recovery.

Equipment Design↗

New silk protein: modification of silk protein by gene engineering for production of biomaterials.

The interest in silk fibroin morphology and structure have increased due to its attractiveness for bio-related applications. Silk fibers have been used as sutures for a long time in the surgical field, due to the biocompatibility of silk fibroin fibers with human living tissue. In addition, it has been demonstrated that silk can be used as a substrate for enzyme immobilization in biosensors. A more complete understanding of silk structure would provide the possibility to further exploit silk fibroin for a wide range of new uses, such as the production of oxygen-permeable membranes and biocompatible materials. Silk fibroin-based membranes could be utilized as soft tissue compatible polymers. Baculovirus-mediated transgenesis of the silkworm allows specific alterations in a target sequence. Homologous recombination of a foreign gene downstream from a powerful promoter, such as the fibroin promoter, would allow the constitutive production of a useful protein in the silkworm and the modification of the character of silk protein. A chimeric protein consisted of fibroin and green fluorescent protein was expressed under the control of fibroin in the posterior silk gland and the gene product was spun into the cocoon layer. This technique, gene targeting, will lead to the modification and enhancement of physicochemical properties of silk protein.

Animals↗

Construction of a novel hydroxyproline-producing recombinant Escherichia coli by introducing a proline 4-hydroxylase gene.

An Escherichia coli recombinant strain producing trans-4-hydroxy-L-proline (Hyp) was constructed by introducing a proline 4-hydroxylase gene into an L-proline-producing E. coli. Plasmid pPF1, which contains a gene encoding feedback resistant gamma-glutamyl kinase (proB74), was constructed and introduced into E. coli W1485 putA. The recombinant E. coli W1485 putA/pPF1 strain produced L-proline (1.2 g/l). The proline production by W1485 putA/pPF1 was converted to Hyp production by introducing pWFH1 which contains a proline 4-hydroxylase gene. E. coli W1485 putA which harbors pWFP1 carrying the proline 4-hydroxylase gene, proB74, and proA produced 25 g/l of Hyp in 96 h. A novel biosynthetic pathway of Hyp, which has not previously been produced in E. coli, was constructed in E. coli.

Journal Article↗

Long-lasting binding of IT-066 to human histamine H2 receptor.

Based on animal models, IT-066, a histamine H2-receptor antagonist, is reported to possess potent and long-lasting antagonisms on histamine H2 receptor (H2R) -mediated effects. However, no reports have been published concerning its interaction with the human H2R. The aim of this study is to characterize its interaction with human H2R. Chinese hamster ovary cell lines stably expressing human H2Rs were obtained. The effects of IT-066, famotidine, and ranitidine on tiotidine binding and histamine-stimulated cAMP production were analyzed. IT-066 inhibited [3H]tiotidine binding and histamine-stimulated cAMP production more potently than famotidine or ranitidine. In addition, preincubation with 10(-5) M IT-066, but not with 10(-5) M famotidine or 10(-4) M ranitidine, had marked inhibitory effects long after extensive washing. Paraformaldehyde fixation of the cells blunted inhibition of [3H]tiotidine binding induced by preincubation with IT-066, but not that by preincubation with famotidine or ranitidine. IT-066 has potent and long-lasting antagonisms on human H2R. At least one of the IT-066 binding sites is not shared by famotidine, ranitidine, or tiotidine and is affected by paraformaldehyde fixation.

Animals↗

Asymmetric cortico-cortical inhibition in patients with progressive limb-kinetic apraxia.

OBJECTIVES: To evaluate the activity of cortico-cortical (intracortical) inhibitory circuits within the motor cortex in patients with progressive asymmetric limb-kinetic apraxia. MATERIALS AND METHODS: We studied 4 patients with progressive limb-kinetic apraxia whose clinical diagnosis was corticobasal degeneration (CBD) and 7 control subjects. Cortico-cortical inhibition was measured using the technique of double pulse transcranial magnetic stimulation over the motor cortex. The effects of conditioning stimuli on the test responses were examined. RESULTS: In the normal control subjects, the conditioning magnetic stimulus suppressed motor evoked responses to the test stimulus at interstimulus intervals of 1 to 5 ms. This inhibition was significantly diminished on the affected side of the patients, but it was normal on the less affected side. CONCLUSION: Disruption of intracortical inhibitory circuits in the motor cortex may, at least in part, be related to severe limb clumsiness in the patients with progressive limb-kinetic apraxia.

Aged↗

A new class of microtubule-associated proteins in plants.

In plants there are three microtubule arrays involved in cellular morphogenesis that have no equivalent in animal cells. In animals, microtubules are decorated by another class of proteins - the structural MAPS - which serve to stabilize microtubules and assist in their organization. The best-studied members of this class in plants are the MAP-65 proteins that can be purified together with plant microtubules after several cycles of polymerization and depolymerization. Here we identify three similar MAP-65 complementary DNAs representing a small gene family named NtMAP65-1, which encode a new set of proteins, collectively called NtMAP65-1. We show that NtMAP65-1 protein localizes to areas of overlapping microtubules, indicating that it may function in the behaviour of antiparallel microtubules in the mitotic spindle and the cytokinetic phragmoplast.

Amino Acid Sequence↗

Colony-forming unit-megakaryocyte (CFR-meg) numbers and serum thrombopoietin concentrations in thrombocytopenic disorders: an inverse correlation in myelodysplastic syndromes.

We studied both serum-free colony-forming unit-megakaryocyte (CFU-meg) numbers and serum thrombopoietin (TPO) levels in 14 patients with aplastic anemia (AA), 37 patients with myelodysplastic syndromes (MDS) and 23 patients with idiopathic thrombocytopenic purpura (ITP) to assess thrombopoiesis in these thrombocytopenic disorders. The mean CFU-meg numbers were lower in AA and MDS patients (10.7 +/- 11.4 and 42.3 +/- 58.5/10(5) BMLD cells) than in healthy controls (103.1 +/- 57.3/10(5) BMLD cells) (P < 0.0001 and P= 0.0053, respectively), although they were distributed variably in MDS. ITP patients showed higher CFU-meg numbers (223.2 +/- 143.5/10(5) BMLD cells) (P= 0.017). The mean TPO concentrations were higher in both AA (986.8 +/- 500.8 pg/ml) and MDS patients (838.2 +/- 639.1 pg/ml) than in healthy controls (80.7 +/- 38.8 pg/ml) (P < 0.0001), although they were distributed from high to low in MDS. ITP patients showed a slight elevation of TPO (123.1 +/- 55.3 pg/ml) P = 0.0106). The TPO levels was inversely correlated to both platelet counts and CFU-meg numbers (correlative coefficient (CC): -0.719 and -0.682, P < 0.0001) in AA, but not in ITP. In MDS, the inverse correlation to TPO was stronger in CFU-meg (CC: -0.678, P < 0.0001) than in platelet counts (CC: -0.538, P = 0.0014), suggesting that CFU-meg plays an important role in regulating TPO production in this heterogenous disorder. CFU-meg and TPO may provide useful information for understanding thrombopoiesis of MDS, especially for application of TPO.

Adolescent↗

Localized phosphorylation of vimentin by rho-kinase in neuroblastoma N2a cells.

BACKGROUND: Vimentin, which is one of the intermediate filaments, is the major cytoskeletal component in developing neurones or neuroblastoma cells. Rho-associated kinase (Rho-kinase), is rich in neurones and is found downstream of Rho. It is involved in the agonist-induced neurite retraction of neuronal cells, and phosphorylates vimentin at Ser-38 and Ser-71 resulting in in vitro disassembly of the filaments. RESULTS: We have investigated the distribution of vimentin phosphorylated by Rho-kinase in N2a neuroblastoma cells using site-specific phosphorylation-dependent antibodies. TM71 immunoreactivity, which specifically indicates Ser-71 phosphorylation on vimentin, was found in some neurites of dibutyryl cAMP-differentiated N2a cells. Transfection of the constitutively active form of Rho-kinase, CAT, significantly elevated TM71 immunoreactivity, and induced neurite retraction or cell rounding. Conversely, transfection of the dominant negative form of Rho-kinase, RB/PH(TT), or treatment of 10 microM Y-27632, a Rho-kinase specific inhibitor, abolished TM71 immuno-reactivity, and induced irregular neurite outgrowth. In contrast, 20 nM okadaic acid (OA) induced neurite retraction and specifically elevated TM71 immunoreactivity. In the OA-induced neurite retraction, tubulin disappeared in retracting neurites, where vimentin and actin remained co-localized. Furthermore, the OA-induced elevation of TM71 immunoreactivity and neurite retraction were completely blocked by pretreatment with 10 microM Y-27632, or by the ectopic expression of RB/PH(TT). CONCLUSIONS: This study suggests that the localized phosphorylation of vimentin by Rho-kinase in neurites was closely related with the cellular morphology of N2a cells, and that the Rho-kinase activity towards vimentin was balanced with OA-sensitive phosphatases.

Amides↗

Genetic dissection of SecA: suppressor mutations against the secY205 translocase defect.

BACKGROUND: The driving force for protein translocation across the bacterial plasma membrane is provided by SecA ATPase, which undergoes striking conformational changes characterized by the membrane insertion and deinsertion cycle. This action of SecA requires the membrane-embedded SecYEG complex. Previously, we have identified a cold-sensitive secY mutation (secY205), affecting the most carboxy-terminal cytosolic domain, that did not allow an ATP-dependent insertion of a SecA-preprotein complex. Thus, this mutant provides an excellent system for genetic analysis of the SecY-SecA interaction. RESULTS: We carried out a systematic isolation of secA mutations that suppressed secY205 cold-sensitivity. A total of 40 independent suppressor mutations were classified into: (i) allele-specific suppressors, acting only against secY205, and (ii) 'super active' suppressors, acting against almost any sec defects. The former class of mutations, presumably with specific effects on the SecY-SecA interaction, clustered in two regions close to the Walker motif A sequences of the two ATP-binding domains. The latter mutations, enhancing general SecA activities, were mostly in or around the minor ATP-binding domain. CONCLUSIONS: The Walker motif A regions of SecA are important for the SecA-SecY interaction that leads to the SecA conformational changes required for insertion into the SecYEG channel. The minor ATP-binding domain is important for the down-regulation of SecA activities.

Adenosine Triphosphatases↗

The R-type pyocin of Pseudomonas aeruginosa is related to P2 phage, and the F-type is related to lambda phage.

Pseudomonas aeruginosa produces three types of bacteriocins: R-, F- and S-type pyocins. The S-type pyocin is a colicin-like protein, whereas the R-type pyocin resembles a contractile but non-flexible tail structure of bacteriophage, and the F-type a flexible but non-contractile one. As genetically related phages exist for each type, these pyocins have been thought to be variations of defective phage. In the present study, the nucleotide sequence of R2 pyocin genes, along with those for F2 pyocin, which are located downstream of the R2 gene cluster on the chromosome of P. aeruginosa PAO1, was analysed in order to elucidate the relationship between the pyocins and bacteriophages. The results clearly demonstrated that the R-type pyocin is derived from a common ancestral origin with P2 phage and the F-type from lambda phage. This notion was supported by identification of a lysis gene cassette similar to those for bacteriophages. The gene organization of the R2 and F2 pyocin gene cluster, however, suggested that both pyocins are not simple defective phages, but are phage tails that have been evolutionarily specialized as bacteriocins. A systematic polymerase chain reaction (PCR) analysis of P. aeruginosa strains that produce various subtypes of R and F pyocins revealed that the genes for every subtype are located between trpE and trpG in the same or very similar gene organization as for R2 and F2 pyocins, but with alterations in genes that determine the receptor specificity.

Amino Acid Sequence↗

Untangling Alzheimer's disease from fibrous lesions of neurofibrillary tangles and senile plaques.

Neuropathological evidence suggests that the two fibril lesions of neurofibrillary tangles (NFT) and senile plaques are the major findings in brain tissue of Alzheimer's disease (AD) and that their occurrence is strongly associated with the symptoms of dementia. Genetic findings have indicated that the pathological molecules from the lesions function as causal agents. There is little evidence, however, to directly indicate that fibril lesions themselves kill neuronal cells in vivo. In spite of such limitations it is important to consider the molecular events involved in AD etiology. In this review of the contribution of Japanese neuropathologists to studies of AD, I will introduce briefly their work and highlight some current topics for consideration on the etiology of AD, and the basis of cell death, and will offer my perspective on outstanding conflicting issues.

Alzheimer Disease↗

Tau protein is a potential biological marker for normal pressure hydrocephalus.

A biological marker for normal pressure hydrocephalus (NPH) is beneficial for evaluation of its severity and of indications for shunt operation. Tau protein was initially considered as a biological marker in cerebrospinal fluid (CSF) from Alzheimer's patients. Recently, it has been demonstrated that degeneration in the brain causes elevation of tau in CSF. Therefore, the tau level in CSF from NPH patients was evaluated. Tau levels in CSF from NPH patients were significantly higher than that in controls. The tau levels were correlated with the severity of dementia, urinary incontinence, and gait disturbance in NPH. These results suggest that CSF tau may be useful as a biological marker for NPH to determine the level of neuronal degeneration.

Aged↗

Primary hepatic leiomyosarcoma in a patient with hepatitis C virus-related liver cirrhosis.

We describe an autopsy case of primary hepatic leiomyosarcoma in a 68-year-old man with hepatitis C virus-related liver cirrhosis. The patient, who had a history of acute hepatitis 20 years previously, died of a ruptured hepatic tumor. At autopsy, a well-circumscribed 14 x 16 x 15 cm tumor replaced the medial site of the right hepatic lobe with multiple intrahepatic and distant metastases. Histologically the tumor, which had extensive central necrosis, consisted predominantly of well or moderately differentiated spindle-shaped cells, which were positive for smooth muscle actin and vimentin on immunohistochemical staining. In addition, clusters of markedly atypical cells and myxoid change of the matrix were discretely found in the focal and small areas of the tumor. These findings indicated that many sections were necessary for the histologically accurate estimation of primary hepatic smooth muscle tumor. The histological examination of a non-tumorous lesion showed liver cirrhosis. Hepatitis C virus was detected in the cytoplasm of cirrhotic hepatocytes by immunohistochemistry and reverse transcriptase-polymerase chain reaction, but not in the tumor cells. This suggested that the virus was not directly involved in the development of primary hepatic leiomyosarcoma.

Actins↗

Predicting the risk of pre-eclampsia and a small-for-gestational-age infant by quantitative assessment of the diastolic notch in uterine artery flow velocity waveforms in unselected women.

OBJECTIVES: To develop a new quantitative index, the notch depth index (NDI), to evaluate its association with the risk of pre-eclampsia and a small-for-gestational-age (SGA) infant and to compare its clinical usefulness with that of the uterine artery resistance index (RI) and the peak systolic to early diastolic velocity (A/C) ratio. METHODS: Uterine artery color Doppler ultrasound was performed in 288 consecutive healthy pregnant women at 20.2 +/- 2.0 (range 16.0-23.9) weeks of gestation. The NDI represents the depth of the early diastolic notch divided by the maximal diastolic velocity. RESULTS: Nine (3.1%) of the 288 women developed pre-eclampsia and 18 women (6.3%) delivered an SGA infant. The NDI was associated with subsequent onset of pre-eclampsia. The optimal cutoff value for the NDI in predicting pre-eclampsia was 0.14, giving a sensitivity, specificity and a positive predictive value (PPV) of 67, 92, and 22%, respectively. The PPV of the NDI was the largest of the three indices evaluated (12% for the RI and 16% for the A/C ratio). The relative risk for pre-eclampsia in women with values equal to or greater than the optimal cutoff values of the RI, A/C ratio and the NDI was 9.7 (95% confidence interval, 2.5-3.7), 19.2 (4.2-91), and 19.2 (5.1-71), respectively. The NDI of 0.14 improved the PPV of 18% determined by the presence of notches in bilateral uterine arteries. The optimal cutoff value of 0.14 for the NDI in predicting an SGA infant yielded a higher PPV (22%) than those for the RI (9%) and A/C ratio (12%). CONCLUSIONS: The NDI value in the second trimester is associated with the later onset of pre-eclampsia, and is clinically more useful in predicting pre-eclampsia than the two conventional indices.

Adult↗