Biomedical subjects

K Mori

Publications and source records attributed to K Mori.

At least 19 recordsLinked to original sources

PubMed2006

DU145 human prostate cancer cells express functional receptor activator of NFkappaB: new insights in the prostate cancer bone metastasis process.

Prostate cancer metastases to bone are observed in around 80% of prostate cancer patients and represent the most critical complication of advanced prostate cancer, frequently resulting in significant morbidity and mortality. As the underlying mechanisms are not fully characterized, understanding the biological mechanisms that govern prostate cancer metastases to bone at the molecular level should lead to the determination of new potential therapeutic targets. Receptor activator of NFkappaB ligand (RANKL)/RANK/Osteoprotegerin (OPG) are the key regulators of bone metabolism both in normal and pathological condition, including prostate cancer bone metastases. In the present study, we demonstrated that human prostate cancer cell lines, DU145 and PC3 express biologically functional RANK. Indeed, soluble human RANKL (shRANKL, 100 ng/ml) treatment induced ERK 1/2, p38 and IkappaB phosphorylations in these cells. shRANKL administration also promoted DU145 and PC3 prostate cancer cell invasion in vitro. Whereas human OPG (hOPG) administration alone (100 ng/ml) had no marked effect, combined association of both agents abolished the RANKL-induced DU145 cell invasion. As RANKL had no direct effect on DU145 cell proliferation, the observed effects were indeed related to RANKL-induced cell migration. DU145 human prostate cancer cells promoted osteoclastogenesis of osteoclast precursors generated from mouse bone marrow. Moreover, DU145 cells produced soluble factor(s) that up-regulate the proliferation of MC3T3-E1 pre-osteoblasts through the activation of the ERK 1/2 and STAT3 signal transduction pathways. This stimulation of pre-osteoblast proliferation resulted in an increased local RANKL expression that can activate both osteoclasts/osteoclast precursors and prostate cancer cells, thus facilitating prostate cancer metastasis development in bone. We confirm that RANKL is a factor that facilitates metastasis to bone by acting as an activator of both osteoclasts and RANK-positive prostate cancer cells in our model. Furthermore, the present study provides the evidence that blocking RANKL-RANK interaction offer new therapeutic approach not only at the level of bone resorbing cells, but also by interfering with RANK-positive prostate cancer cells in the prostate cancer bone metastasis development.

3T3 Cells↗

PubMed2006

Pressure effect in a shock-wave-plasma interaction induced by a focused laser pulse.

The effect of ambient pressure on the interaction between a laser plasma bubble and a shock wave involving a Richtmyer-Meshkov instability was experimentally studied via framing Schlieren visualization. A sharp plasma interface could be formed without any separation material that causes undesired disturbances. The fundamental vortex structure which was produced via baroclinic effects was self-similar with respect to the laser energy-ambient pressure ratio. Yet, the higher the ambient pressure, the more high-wave-number instabilities were enhanced so as to contaminate the self-similarity.

Journal Article↗

PubMed2006

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice.

AIMS/HYPOTHESIS: Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. MATERIALS AND METHODS: We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. RESULTS: After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-beta and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. CONCLUSIONS/INTERPRETATION: Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.

Animals↗

PubMed2006

Maturation-dependent change and regional variations in acoustic stiffness of rabbit articular cartilage: an examination of the superficial collagen-rich zone of cartilage.

OBJECTIVE: The purpose of the study was to investigate maturation-dependent changes of acoustic (ultrasound) stiffness and other ultrasound features of articular cartilage in healthy rabbit knees. METHODS: Five groups of rabbits of various ages (3 weeks, 8 weeks, 6 months, 1 year, 2.5 years) consisting of five rabbits per group were examined. Signal intensity (index of stiffness), signal duration (index of surface irregularity) and interval between signals (index of thickness) of the ultrasound reflection from articular cartilage were examined at four sites: posterior lateral femoral condyle, posterior medial femoral condyle, lateral tibial plateau, and medial tibial plateau. The sites were observed macroscopically and microscopically with a light microscope and a polarized light microscope. RESULTS: At the lateral and medial condyles and the lateral tibial plateau, signal intensity was least in 3-week-old specimens. The intensity increased until 6 months or 1 year of age. At these sites, the signal durations and intervals between signals were least at the ages of 6 months or 1 year. At the medial tibial plateau, the intensity was the least at 2.5 years of age and the interval between signals was least at 3 weeks of age; there was no effect of age on signal duration. Cartilage surfaces of all specimens were smooth and no degenerative changes were macroscopically or microscopically evident. The surface brightness of cartilage under the polarized light microscope was consistent with signal intensity values. CONCLUSIONS: The response of articular cartilage to ultrasound was maturation-dependent. Acoustic properties differed from mechanical stiffness properties, which were determined using indentation. Ultrasound may detect properties of the surface collagen of the articular cartilage.

Aging↗

PubMed2006

Enhanced selenium effect on growth arrest by BiP/GRP78 knockdown in p53-null human prostate cancer cells.

Redox modification of thiol/disulfide interchange in proteins by selenium could lead to protein unfolding. When this occurs in the endoplasmic reticulum (ER), a process known as unfolded protein response (UPR) is orchestrated for survival through activation of PERK-eIF2alpha (PERK: double-stranded RNA-activated protein kinase-like ER kinase; eIF2alpha: eucaryotic initiation factor 2alpha), ATFalpha (ATFalpha: activating transcription factor 6) and inositol requiring 1 (IRE1)-x-box-binding protein 1 (XBP1) signalings. All three UPR transducer pathways were upregulated very rapidly when PC-3 cells were exposed to selenium. These changes were accompanied by increased expression of UPR target genes, including immunoglobulin heavy chain-binding protein/glucose-regulated protein, 78 kDa and CCAAT/enhancer binding protein-homologous protein/growth arrest- and DNA damage-inducible gene (CHOP/GADD153). Induction of BiP/GRP78, an ER-resident chaperone, is part of the damage control mechanism, while CHOP/GADD153 is a transcription factor associated with growth arrest and apoptosis in the event of prolonged ER stress. Knocking down BiP/GRP78 induction by small interference RNA produced a differential response of the three transducers to selenium, suggesting that the signaling intensity of each transducer could be fine-tuned depending on BiP/GRP78 availability. In the presence of selenium, CHOP/GADD153 expression was raised even higher by BiP/GRP78 knockdown. Under this condition, the selenium effect on wild-type p53-activated fragment p21 (p21(WAF)), cyclin-dependent kinase (CDK)1 and CDK2 was also magnified in a manner consistent with enhanced cell growth arrest. Additional experiments with CHOP/GADD153 siRNA knockdown strongly suggested that CHOP/GADD153 may play a positive role in upregulating the expression of p21(WAF) in a p53-independent manner (PC-3 cells are p53 null). Collectively, the above findings support the idea that UPR could be an important mechanism in mediating the anticancer activity of selenium.

CDC2 Protein Kinase↗

PubMed2006

Endoscopic hematoma evacuation for hypertensive cerebellar hemorrhage.

OBJECT: The management of spontaneous cerebral hemorrhage remains controversial, particularly the surgical indications. Endoscopic surgery was evaluated for the treatment of spontaneous cerebellar hemorrhage. METHODS: The records of 69 patients with hypertensive cerebral hemorrhage were retrospectively reviewed. Patients treated by endoscopic surgery (n = 10) were compared with patients treated by conventional surgical hematoma evacuation (n = 10) under the same surgical indications. RESULTS: The surgical procedure time, duration of ventricular drainage, extent of hematoma evacuation, necessity for cerebrospinal fluid (CSF) shunt, surgical complications, and outcome at discharge and at 3 months after onset were compared. The extent of hematoma evacuation was greater in the endoscopic group (95.2 %) than in the craniectomy group (90.6 %) but without significant difference. The endoscopic technique (64.5 min) took significantly less time than the craniectomy method (230.6 min, p < 0.0001). The period of ventricular drainage was significantly shorter in the endoscopic group (2.6 days) compared to the craniectomy group (12.3 days, p < 0.01). CSF shunt surgery was required in no patient in the endoscopic group compared to three in the craniectomy group. CONCLUSION: Endoscopic hematoma evacuation is a rapid, effective, and safe technique for the removal of hypertensive cerebellar hemorrhage. Reduction of the mass effect can be accomplished with low risk of recurrent hemorrhage. Release of obstructive hydrocephalus in the early stage may improve the patient's outcome and decrease the requirement for permanent shunt emplacement.

Aged↗

PubMed2006

Intravenous immunoglobulin treatment in painful sensory neuropathy without sensory ataxia associated with Sjögren's syndrome.

Patients having neuropathy associated with Sjögren's syndrome may present with pain and superficial sensory involvement in the absence of sensory ataxia. Treatment for this form of associated neuropathy has not been established. The case of a patient with painful sensory neuropathy associated with Sjögren's syndrome, whose symptoms, particularly pain, responded well to intravenous immunoglobulin both at onset and in a relapse, is reported. Other patients with painful sensory neuropathy associated with Sjögren's syndrome may also be candidates for intravenous Ig treatment.

Aged↗

PubMed2006

Closed reduction for traumatic posterior dislocation of the shoulder using the 'lever principle': two case reports and a review of the literature.

Traumatic posterior dislocation of the shoulder is frequently missed because of its rarity and the absence of characteristic symptoms. Several signs should be emphasised: an overlap of the humeral head and glenoid rim in a true anteroposterior view and the light-bulb sign in the anteroposterior view. To make an accurate and early diagnosis, use of multidirectional radiographs combined with computed tomography is recommended. Closed reduction was successfully performed under general anaesthesia using the DePalma method with slight modification--the lever principle--by pushing the medial side of the upper arm laterally to adduct the shoulder as far as possible. The dynamics of the lever principle make it a safer and more effective method of achieving a closed reduction of a posterior dislocation of the shoulder than the conventional method of solely pushing the humeral head anteriorly, especially in patients with locking of the glenohumeral joint and impression fractures.

Aged↗

PubMed2006

[Evaluation of imaging before lung volume reduction surgery for pulmonary emphysema; fused image of multi-detector row computed tomography and scintigram].

Lung volume reduction surgery (LVRS) is performed as surgical therapy for severe pulmonary emphysema. In assessing diagnostic imaging indications, emphysematous change is the strongest in the thoracic computed tomography (CT), while the accumulation decrease is most remarkable in ventilation scintigram and lung perfusion scintigram. Preoperative evaluation of imaging using multidetector-row CT (MDCT) and scintigram were performed, and the multiplanar reconstruction (MPR) image of the MD CT and the single photon emission CT (SPECT) image of the scintigram were fused by the workstation. It was possible to evaluate the excision and the range of LVRS easily by looking at the fused image, and it was useful in deciding on the surgical approach. It is believed that accurate, comprehensible imaging information contributed to an improvement in the surgical outcome of LVRS.

Evaluation Studies as Topic↗

PubMed2005

Clinicopathologic features of nonsystemic vasculitic neuropathy and microscopic polyangiitis-associated neuropathy: a comparative study.

OBJECTIVE: To compare clinicopathologic findings in nonsystemic vasculitic neuropathy (NSVN) and microscopic polyangiitis-associated neuropathy (MPAN). METHODS: Patients clinicopathologically confirmed to have NSVN (n=23) or MPAN (n=40) were compared with respect to clinical, electrophysiologic, and histopathologic features. RESULTS: Clinical features of neuropathy such as initial symptoms, progression, and distribution of sensory and motor deficits were similar in both groups, while functional compromise was greater in MPAN than NSVN. Abnormalities of laboratory data including those reflecting severity and extent of inflammation such as C-reactive protein were more conspicuous in MPAN than NSVN. Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were positive in two-thirds of patients with MPAN but negative in all NSVN. Electrophysiologic and histopathologic findings indicated axonal neuropathy in both groups, whereas the reduction of compound muscle action potentials in the tibial nerve and sensory nerve action potentials in the median nerve was significantly more profound in MPAN than NSVN. As for the epineurial perivascular infiltration, frequencies of cell-specific markers for T lymphocytes, macrophages, and B lymphocytes among cells infiltrating the vasculitic lesions were essentially similar between groups. CONCLUSIONS: Clinicopathologic profiles and vascular pathology were similar between NSVN and MPAN but the age at onset, severity, and presence of p-ANCA were clearly different. Further study is needed to clarify the pathogenesis of NSVN and its place in the vasculitic spectrum of diseases.

Action Potentials↗

PubMed2005

(1S,3S,7R)-3-methyl-alpha-himachalene from the male sandfly Lutzomyia longipalpis (Diptera: Psychodidae) induces neurophysiological responses and attracts both males and females.

Lutzomyia longipalpis adult males form leks on or near hosts and release (1S,3S,7R)-3-methyl-alpha-himachalene from their tergal glands to lure females to the same site for mating and feeding. Here we have examined whether the male-produced attractant could also serve as a male aggregation stimulus. High resolution chiral capillary gas chromatography analysis of male tergal gland extracts, synthetic (1S,3S,7R)-3-methyl-alpha-himachalene, and a synthetic mixture of all isomers of 3-methyl-alpha-himachalene, was coupled to electrophysiological recordings from ascoid sensillum receptor cells in antennae of male and female sandflies. Receptor cells of both sexes responded only to the main component of the male tergal gland extract that eluted at the same retention time as (1S,3S,7R)-3-methyl-alpha-himachalene. Furthermore, of the eight 3-methyl-alpha-himachalene isomers in the synthetic mixture only the fraction containing (1S,3S,7R)-3-methyl-alpha-himachalene, co-eluting with an isomer of (1S*,3S*,7S*)-3-methyl-alpha-himachalene, elicited an electrophysiological response from male and female ascoid sensillum receptor cells. Both males and females flew upwind in a wind tunnel towards a filter paper disk treated with either 4-6 male equivalents of the tergal gland extract, pure (1S,3S,7R)-3-methyl-alpha-himachalene or the synthetic mixture of eight isomers. This indicates that (1S,3S,7R)-3-methyl-alpha-himachalene derived from L. longipalpis males may have a dual function in causing male aggregation as well as serving as a sex pheromone for females.

Action Potentials↗

PubMed2005

Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma.

BACKGROUND: Osteosarcoma is the most common type of primary bone tumor. The use of aggressive chemotherapy has drastically improved the prognosis of the patients with non-metastatic osteosarcomas, however the prognosis of the patients with metastasis is still very poor. Then, new and more effective treatments for curing osteosarcoma, such as immunotherapy are needed. Tumor-infiltrating lymphocytes (TIL) have been involved in the control of tumor development and already assessed with success for the treatment of several cancers including melanoma. While TIL represent a fascinating therapeutic approach in numerous malignant pathologies, there is few report concerning adult bone-associated tumors including osteosarcoma. METHODS: Human TIL were isolated and characterized (phenotype, lytic activity) from twenty-seven patients with bone-associated tumors (osteosarcoma, Ewing's sarcoma, giant cell tumor, chondrosarcoma, plasmocytoma and bone metastases). Similar experiments were performed using rat osteosarcoma model. RESULTS: While TIL with a main CD4+ profile were easily isolated from most of the tumor samples, only TIL extracted from osteosarcoma were cytotoxic against allogeneic tumor cells. In all cases, TIL lytic activity was significantly higher compared to autologous peripheral blood leukocytes. Similar data were observed in rat osteosarcoma model where TIL were characterized by a main CD4+ profile and high lytic activity against allogeneic and autologous tumor cells. Moreover, rat TIL expansion was not accompanied by refractoriness to further activation stimulus mainly by tumor antigens. CONCLUSION: These results demonstrated that TIL therapy could be a very efficient strategy for the treatment of adult osteosarcoma.

Adolescent↗

PubMed2005

Preliminary study of using imaging plates to map skin dose of patients in interventional radiology procedures.

A method using europium-doped BaFBr imaging plates (IPs) has been studied for mapping entrance skin doses during interventional radiology (IR); the mapping is useful for detecting overlap between irradiation fields and determining the most exposed skin areas. IPs, which are two-dimensional radiation sensors made of photostimulated luminescence materials, have a linear dose response up to approximately 100 Gy, can accurately measure doses from 1 microGy to 10 Gy and can be used repeatedly. Because the energy dependence of IPs is rather high, the IPs were characterised in this study and a sensitivity variation of approximately 13% was observed for effective energies of 32.7 to 44.7 keV, which are used in IR procedures. Simulation of actual interventional cardiology procedures showed that the variation of sensitivity was within 5%, meaning that IPs are practical for measuring skin doses during IR. Moreover, the patient data can be stored online and easily called up when IR procedures must be repeated, helping to prevent radiation injuries.

Dose-Response Relationship, Radiation↗

PubMed2005

Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP.

To identify clinical and electrophysiologic features related to IV immunoglobulin (IVIg) responsiveness in chronic inflammatory demyelinating polyneuropathy (CIDP), the authors conducted a multicenter study on 312 patients with CIDP (199 responders and 113 nonresponders). Muscle atrophy and decreased compound muscle action potential were pronounced in nonresponders of IVIg. Male gender, longer disease duration, and slow progression of symptoms were also associated with IVIg unresponsiveness. Features suggesting axonal dysfunction in peripheral nerves indicated IVIg unresponsiveness in CIDP.

Adult↗

PubMed2005

Gene expression profiles in human gastric cancer: expression of maspin correlates with lymph node metastasis.

To seek for a candidate gene that would regulate tumour progression and metastasis in gastric cancer, we investigated gene expression profiles by using DNA microarray. Tumour tissue and adjacent normal tissue were obtained from 21 patients with gastric cancer and then examined for their gene expression profiles by the Gene Chip Human U95Av2 array, which includes 12 000 human genes and EST sequences. A total of 25 genes were upregulated and two genes were downregulated by at least four-fold in the tumour tissue. In a further analysis according to lymph node metastasis, the expressed levels of maspin, as well as carcinoembryonic antigen and nonspecific crossreacting antigen were significantly higher in tumours with lymph node metastasis than in those without it. Maspin expression in 85 gastric cancer patients was further investigated by using immunohistochemistry. Maspin expression was not observed in normal gastric epithelia without intestinal metaplasia. In contrast, maspin was expressed in 74 of 85 tumour tissues. There was a significant correlation between the incidence of maspin-positive tumour staining and lymph node metastasis. These results suggest that maspin has a potential role for tumour metastasis in gastric cancer.

Adult↗

PubMed2005

Spontaneous lymphocyt ic thyroiditis in interferon regulatory factor-1 deficient non-obese diabetic mice.

Interferon regulatory factor-1 (IRF-1) is a transcription factor involved in interferon-mediated immune reaction, CD8+ T cell differentiation and development of T helper 1 immune reaction. We have recently demonstrated that IRF-1 is pivotal in iodine-induced lymphocytic thyroiditis (LT) in non-obese diabetic (NOD) mice. However, it remains unclear whether the mechanism involved in spontaneous LT is identical with iodine-induced LT in NOD mice. To determine the role of IRF-1 in spontaneous LT, we used IRF-1 deficient NOD mice as well as IRF-1 +/+ and +/- mice which were free from treatments for LT induction, and LT was evaluated at 24 weeks of age. IRF-1 +/+, +/- and -/- mice developed LT spontaneously, and there were no differences among the 3 IRF-1 genotypes in the incidence and severity of LT. Whereas both CD4+ and CD8+ T cells were present in the diseased thyroid of IRF-1 +/+ mice, CD8+ T cells were absent in the thyroid of IRF-1 -/- mice. MHC class II antigen expression was induced in the inflamed thyroid of IRF-1 -/- mice comparable to IRF-1 +/+ mice. There was a selective reduction in the number of CD8+ T cells in the spleen of IRF-1 -/- mice. IFNgamma production, but not IL-10, by concanavalin A-stimulated splenocytes was significantly reduced in IRF-1 deficient mice. These results suggest that IRF-1 plays only a minor role in spontaneous LT in NOD mice and, furthermore, the mechanism involved in spontaneous LT is different from that of iodine-induced LT in NOD mice.

Animals↗

PubMed2005

Identification of sex pheromone components of the painted apple moth: a tussock moth with a thermally labile pheromone component.

The sex pheromone of the painted apple moth, Teia anartoides (Lymantriidae) was investigated using GC-EAD and GC-MS analysis, derivatization, TLC analysis, and field cage and field trapping bioassays. The major sex pheromone components were identified as (6Z,9Z)-henicosa-6,9-dien-11-one and (6Z,9Z)-henicosa-6,9-diene. Other minor components of pheromone gland extracts included (6Z)-9R, 10S-epoxyeicos-6-ene, (6Z)-9R,10S-epoxyhenicos-6-ene, (6Z,9Z)-henicosa-6,9-dien-11-ol, (6Z)-henicos-6-en-11-one, and (6Z, 8E)-henicosa-6,8-dien-11-one, but the roles of these minor components remain equivocal. In field cage and field experiments, a blend of all seven identified components [(6Z,9Z)-henicosa-6,9-dien-11-one (relative amount 100), (6Z,9Z)-henicosa-6,9-diene (100), (6Z)-9R,10S-epoxyeicos-6-ene (5), (6Z)-9R,10S-epoxyhenicos-6-ene (10), (6Z,9Z)-henicosa-6,9-dien-11-ol (5), (6Z)-henicos-6-en-11-one (1), and (6Z,8E)-henicosa-6,8-dien-11-one (25)] was as attractive to males as calling females, but tests with blends of the major component(s) with subsets of the minor components did not produce consistent results that unequivocally showed the various minor components to be critical components of the active blend. (6Z,9Z)-henicosa-6,9-dien-11-one is thermally labile and rearranges to (6Z,8E)-henicosa-6,8-dien-1-one and other products at ambient temperature, rendering the synthetic pheromone lure inactive after two days of field exposure.

Animals↗

PubMed2005

Sentinel surveillance for international Shigella by a quarantine station in Japan.

The Japanese quarantine system monitors incoming passengers to detect imported pathogens at international airports. At one airport, we found that 74% of 13 315 travellers returning with diarrhoea had visited only one country before entering Japan. On the basis of our results, we hypothesized that the international distribution and potential source of bacterial strains could be inferred by analysing strains isolated from travellers returning to Japan. In order to demonstrate the potential for this system, we randomly selected five Shigella sonnei strains and examined their restriction fragment length polymorphism patterns. One set of strains appeared to be closely related, while three sets, isolated from travellers who visited different countries were possibly related. These results suggest that international distributions and potential sources of S. sonnei may be inferred by monitoring isolates from passengers arriving at a Japanese quarantine station.

Aircraft↗