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Biomedical subjects

I Nakamura

Publications and source records attributed to I Nakamura.

At least 109 records · Page 6Linked to original sources
PubMed1998

Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common form of human myelopathy caused by a compression of the spinal cord by ectopic ossification of spinal ligaments. To elucidate the genetic basis for OPLL, we have been studying the ttw (tiptoe walking; previously designated twy) mouse, a naturally occurring mutant which exhibits ossification of the spinal ligaments very similar to human OPLL (refs 3,4). Using a positional candidate-gene approach, we determined the ttw phenotype is caused by a nonsense mutation (glycine 568 to stop) in the Npps gene which encodes nucleotide pyrophosphatase. This enzyme regulates soft-tissue calcification and bone mineralization by producing inorganic pyrophosphate, a major inhibitor of calcification. The accelerated bone formation characteristic of ttw mice is likely to result from dysfunction of NPPS caused by predicted truncation of the gene product, resulting in the loss of more than one-third of the native protein. Our results may lead to novel insights into the mechanism of ectopic ossification and the aetiology of human OPLL.

Animals↗
PubMed1998

'Chiyamai', a panic-like disorder in woman divers from Hegura Island.

In Hegura Island, Japan, we have recently found female divers who suffer from a disorder called 'Chiyamai'. From interviews, questionnaires and temporarily proposed diagnostic criteria for Chiyamai, nine cases from 44 female divers interviewed, were diagnosed as having Chiyamai. Clinically, Chiyamai is characterized by a panic-like attack. Ten symptoms were observed during a panic-like attack, compared with 13 symptoms in a panic attack described in the DSM-IV. The average age at onset was 30 years and the average duration of illness was approximately 26 years. Several cases were so severe that the patients were unable to continue diving. Additionally, we report a typical case of Chiyamai, and discussed the similarities and differences between Chiyamai and anxiety disorders in the DSM-IV. We suggest that Chiyamai is a panic-like disorder specific to female divers from Hegura Island and that it is a result of heavy diving.

Adult↗
PubMed1998

A quantitative study of neurofibrillary tangles, senile plaques and astrocytes in the hippocampal subdivisions and entorhinal cortex in Alzheimer's disease, normal controls and non-Alzheimer neuropsychiatric diseases.

The present quantitative study was performed in order to discriminate pathological substrates for dementia from Alzheimer changes in normal controls (NC) and non-Alzheimer neuropsychiatric diseases (NAND). Regional densities of senile plaques (SP), neurofibrillary tangles (NFT) and astrocytes in the cornu ammonis (CA), subiculum and entorhinal cortex were measured and differences in these densities among Alzheimer's disease (AD), NAND and NC were statistically compared. Densities of NFT in the CA and subiculum were significantly higher in AD than in NAND, and densities of SP in all regions were significantly higher in AD than in NAND. Similarly, NFT density in the subiculum and SP density in all regions were higher in AD than in NC. Regional densities of astrocytes in most regions were closely correlated with those of Alzheimer changes. In conclusion, the attribution of the Alzheimer changes, particularly of NFT, to dementia is neglected when they are confined to the entorhinal cortex. However, the attribution of the Alzheimer changes to dementia should be appreciated when they spread from the entorhinal cortex to the subiculum and/or CA.

Adult↗
PubMed1998

Construction and voiding functions of three types of orthotopic neobladders using colonic segments: the Kobe University experience.

BACKGROUND: At Kobe University Hospital we have created orthotopic neobladders since 1988 by using several colonic segments. Various types of neobladders were compared and a detailed description of these procedures and the voiding function outcome is presented. METHODS: Thirty-two men with invasive bladder carcinoma or recurrent carcinoma in situ underwent a radical cystectomy followed by orthotopic neobladder replacement using a right colonic, ileocolic or sigmoid colonic segment. The functional capacity, percentage of residual urine volume, configuration of the neobladder, and location in the pelvis were evaluated 1 year after surgery. Voiding function was evaluated using a questionnaire which included questions on diurnal and nocturnal continence, and by uroflowmetric analysis. RESULTS: Operative time, blood loss, and functional neobladder capacity did not differ for the 3 types of neobladders. The configuration of the right colonic and ileocolic neobladders resembled the shape of a rugby ball. The configuration of the sigmoid neobladder was oval. The right colonic and ileocolic neobladders tended to be located along the right side wall of the pelvis. The sigmoid neobladder was located in the center of the pelvis. Daytime and nocturnal continence was not affected by either the type of neobladder or its configuration or position. Neobladders located in the center of the pelvis exhibited a better maximum flow rate than those located along the right wall of the pelvis. CONCLUSION: The technical difficulty in constructing the 3 types of neobladders was approximately the same. For better voiding a neobladder should be located in the center of the pelvis.

Aged↗
PubMed1998

Echistatin inhibits the migration of murine prefusion osteoclasts and the formation of multinucleated osteoclast-like cells.

The vitronectin receptor alpha(v)beta3 is highly expressed in osteoclasts and was shown to play a critical role in osteoclast function in vivo. The objective of this study was to examine the role of alpha(v)beta3 integrin in osteoclast formation in vitro using the inhibitory disintegrin echistatin, an RGD-containing snake venom. We documented by immunocytochemistry and Northern blot analysis that during murine osteoclast-like cell (OCL) formation in a coculture of mouse osteoblastic MB1.8 cells and bone marrow cells there is increased expression of the alpha(v) and beta3 integrin subunits. Echistatin binds preferentially to the membrane fraction of isolated enriched OCLs (IC50 = 0.6 nM), and this binding is inhibited by vitronectin receptor-blocking polyclonal antibodies. Additionally, cross-linking of radiolabeled echistatin to OCLs, followed by immunoprecipitation with antibodies to vitronectin or fibronectin receptors, shows that alpha(v)beta3 integrin is the predominant receptor for echistatin in this system. In this coculture, echistatin completely inhibits the formation of multinucleated OCLs, but not that of mononuclear prefusion OCLs (pOCs). This inhibition is RGD and dose dependent (IC50 = 0.7 nM). We tested the hypothesis that inhibition of OCL formation may be due to interference with pOC migration and found that echistatin inhibited macrophage colony-stimulating factor-induced migration and fusion of pOCs (IC50 = 1 and 0.6 nM, respectively). Echistatin inhibition of pOCs migration and fusion is also RGD dependent. These results suggest that the integrin alpha(v)beta3 plays a role in pOC migration, which can explain the inhibitory effect of echistatin on multinucleated osteoclast formation in vitro.

Animals↗
PubMed1998

[Comparison of propofol and pentazocine combined with thiamylal for laryngeal mask insertion].

We evaluated the combination of pentazocine and thiamylal as induction agents for laryngeal mask airway (LMA) insertion and compared this with propofol. Ninety-four patients, ASA grade 1 or 2, were randomly assigned to one of four induction groups as follows; group P: propofol 2.5 mg.kg-1, group p 0.3: pentazocine 0.3 mg.kg-1 followed by thiamylal 5 mg.kg-1, group p 0.6: pentazocine 0.6 mg.kg-1 followed by thiamylal 5 mg.kg-1, and group T: thiamylal 5 mg.kg-1. In group T (n = 5), insertion of LMA was impossible due to inadequate anesthesia. In contrast, good and acceptable conditions for LMA insertion were obtained in 85.2%, 86.7%, and 96.9% of group P, p 0.3, and p 0.6, respectively. Apneic interval, endtidal CO2 and arterial CO2 were significantly greater in pentazocine groups than in propofol group (group P < p 0.3 < p 0.6). Systolic pressure decreased after induction in all groups. Decreases in systolic and diastolic pressure were significantly greater in group P. Heart rate did not show any significant change. We conclude that the induction with the combination of pentazocine and thiamylal provides suitable conditions for LMA insertion with more stable hemodynamics compared with propofol. Doses of 0.3 mg.kg-1 seem to be desirable for LMA insertion.

Adjuvants, Anesthesia↗
PubMed1997

Transcriptional regulation of the mBMP-4 gene through an E-box in the 5'-flanking promoter region involving USF.

We analyzed the promoter activity of murine bone morphogenetic protein-4 (mBMP-4) and determined that the 5'-flanking region of exon I plays a critical role for transcription and position -265 to -246 of 5'-flanking region of mBMP-4 gene acts as a cis-element important for the regulation of BMP4 transcription in MC3T3E1 cells. By use of site-directed mutagenesis, we have established that the E-box, CACGTG, located within this short region of promoter, is essential for transcriptional activation of the mBMP-4 gene. Upstream stimulatory factor (USF), a member of the helix-loop-helix (HLH) group of regulatory proteins, was found to bind to this E-box using supershift gel mobility analysis. It is proposed that the HLH transcription regulatory proteins play an important role in mBMP-4 gene transcription in this osteoblastic cell line.

Animals↗
PubMed1997

Effect of beryllium chloride on porphyrin metabolism in pregnant mice administered by subcutaneous injection.

The effect of beryllium (Be) compounds on porphyrins was investigated in pregnant mice. The blood protoporphyrin (Proto) and zinc protoporphyrin (Zn Proto) concentrations were increased in pregnancy. Regardless of pregnancy or nonpregnancy, the Proto concentration was decreased after Be injection. Delta-aminolevulinic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D) activities in blood were significantly elevated in the pregnant untreated (Con-pregnant) group, compared to the nonpregnant mice untreated (Con-nonpregnant) and nonpregnant mice treated with Be (Be-nonpregnant) groups. The blood ALA-D activity of the pregnant mice treated with Be (Be-pregnant group) tended to decrease, compared to Con-pregnant group. The blood PBG-D activity in the Be-pregnant group was significantly lower compared with that of the Con-pregnant group. The ALA-D and PBG-D activities in the spleen were also significantly elevated in the Con-pregnant group, compared to nonpregnant groups. However, it was noted that these values in the Be-pregnant group were almost the same as that of the Con-nonpregnant group and were significantly lower than that in the Con-pregnant group. The elevation of ALA-D and PBG-D activities in the blood and spleen, which play a role in the hematopoietic function of mice, was observed in the Con-pregnant mice compared to the nonpregnant mice. However, the phenomenon was not observed in the Be-pregnant mice, it suggesting that Be suppressed the pregnancy-induced increase in hematopoietic function.

Animals↗
PubMed1997

Lack of vacuolar proton ATPase association with the cytoskeleton in osteoclasts of osteosclerotic (oc/oc) mice.

We examined the pathogenetic mechanism underlying the lack of bone resorption in osteosclerotic oc/oc mice. An immunoelectron microscopic analysis revealed that in the osteoclasts of these mice, no ruffled borders formed, and that vacuolar H+-ATPase (V-ATPase) was present throughout the cytoplasm but not on the apical membranes. The activity of V-ATPase in oc/oc mice was similar to that in normal mice. In normal spleen cell-derived osteoclast-like cells (OCLs), immunoreactivity for V-ATPase was detected in association with Triton X-100-insoluble cellular structure, but not in oc/oc spleen cell-derived OCLs. Moreover, in renal proximal convoluted tubules of oc/oc mice, the basal striation did not form. These results suggest that osteosclerosis in oc/oc mice is possibly due to the dissociation of V-ATPase and cytoskeleton in osteoclasts.

Adenosine Triphosphatases↗
PubMed1997

Cloning and characterization of partial cDNAs for woodchuck cytokines and CD3epsilon with applications for the detection of RNA expression in tissues by RT-PCR assay.

Immunologic reagents and methodology are essential to develop further the woodchuck and woodchuck hepatitis virus (WHV) as a model of immune response, inflammation, and immunotherapy in hepatitis B virus (HBV) infection. Partial cDNA clones for the woodchuck CD3epsilon marker of T cells (536 bp) and for selected woodchuck cytokines were developed, including IL-1beta (332 bp), IL-2 (249 bp), IL-4 (205 bp), IL-10 (476 bp), IFN-gamma (476 bp), and TNF-alpha (381 bp). This panel of markers includes sets to measure RNAs for T cells (CD3epsilon), immune response induction (IL-1beta, IL-2), TH subsets (TH1, IL-2/IFN-gamma vs. TH2, IL-4/IL-10), and effector molecules that regulate hepadnavirus replication and liver injury (IFN-gamma, TNF-alpha). Primers representing highly conserved segments of genes from other species were used to derive the partial cDNA clones. Target RNA was obtained from woodchuck peripheral blood mononuclear cells (PBMC) that were stimulated in vitro with ConA, LPS, and human rIL-2. The cDNA clones were validated by 1) comparison with other species for homologies in the nucleotide and predicted amino acid sequences and 2) a first generation assay demonstrating induction of the respective RT-PCR products in stimulated woodchuck PBMC. The corresponding RNAs were also detectable in most cases in the total RNA from the livers of uninfected and WHV-infected woodchucks and differential expression of IFN-gamma and TNF-alpha RNAs was suggested. Second generation, semi-quantitative assays for the RNAs were validated using RT-PCR and dot-blot hybridization with 32P-oligomers derived from the internal sequences of the respective clones. Continued study of the woodchuck immune response to WHV infection using these assays will provide insight into the kinetics and immune mechanisms that initiate and maintain chronic hepadnavirus infection and, hence, enable development of improved immunotherapies for established chronic HBV infection.

Amino Acid Sequence↗
PubMed1997

Phosphatidylinositol-3 kinase is involved in ruffled border formation in osteoclasts.

Phosphatidylinositol (PI)-3 kinase has been implicated in several aspects of intracellular membrane trafficking, although the detailed mechanism is yet to be established. We previously reported that wortmannin (WT), a selective inhibitor of PI-3 kinase, inhibited the bone-resorbing activity of osteoclasts (Nakamura et al., 1995, FEBS Lett., 361:79-84). In this study, we examined how PI-3 kinase was involved in membrane trafficking in osteoclasts which are primary bone-resorbing cells. Osteoclasts exhibit a highly polarized cytoplasmic organization, the ruffled border. Ruffled borders are formed by numerous deep membrane invaginations, on which vacuolar H(+)-ATPase (V-ATPase) is localized in a high density. Immunoelectron microscopic analyses revealed that PI-3 kinase was specifically present along ruffled border membranes and the limiting membranes of associated intracellular vacuoles in rat authentic osteoclasts. WT and LY294002, another inhibitor of PI-3 kinase, caused the accumulation of numerous acidic vacuoles which were stained with acridine orange in murine osteoclast-like multinucleated cells formed in vitro. An electron microscopic examination showed that these vacuoles contained V-ATPase along their limiting membranes and appeared to be derived from the Golgi apparatus as ruffled border precursors. A time course study revealed that WT-induced vacuoles began to accumulate in the region close to the apical membrane and were finally distributed throughout the cytoplasm. Removal of WT from the culture medium resulted in the disappearance of vacuoles in the cytoplasm, leading to the formation of ruffled borders. During the culture period, some vacuoles were observed to fuse with the ruffled border membrane. A pit formation assay on dentine slices also showed that the pit-forming activity of osteoclast-like cells was recovered by the removal of WT from the assay. These results suggest that PI-3 kinase plays an important role in ruffled border formation in osteoclasts, probably in the fusion of membrane vacuoles with the plasma membrane.

Androstadienes↗
PubMed1997

Sudden unexpected death due to Fournier's gangrene.

A 43-year-old Japanese male vagrant collapsed suddenly in a police station. The man was resuscitated in hospital but died about 13 h later. An autopsy revealed necrotizing fasciitis in the genitalia and lower abdominal wall. The man was considered to have died from endotoxic shock following on Fournier's gangrene.

Adult↗
PubMed1997

Association between angiotensin converting enzyme gene polymorphism and clinical features in autosomal dominant polycystic kidney disease.

We investigated the association between angiotensin converting enzyme (ACE) gene polymorphism and clinical manifestations in 47 patients with autosomal dominant polycystic kidney disease (ADPKD). One-hundred, age- and sex-matched subjects with non-ADPKD served as the controls. ACE gene polymorphism was analysed using a GeneAnp kit. Renal size was determined by abdominal CT scan, by adding the longitudinal axis of each kidney. Incidence of extrarenal complication was also examined. Out of 47 patients, 24 patients (51%) were II, 18 (38%) ID and 5 (11%) DD type. The frequencies of the I and D alleles as well as the distributions of ACE genotypes in ADPKD did not differ from those in controls. The number of patients undertaking renal replacement therapy was 11 in II (46%), 6 (33%) in ID and 2 (40%) in DD genotype, respectively, that was not significantly different among the groups. The mean age of the initiation of renal replacement therapy did not vary among the three genotypes. The slopes of 1/serum creatinine did not differ between II and ID genotypes, whose initial serum creatinine levels ranged from 1.5 to 2.5 mg/dl. Renal size, blood pressure, and extrarenal complications including liver cysts and cardiac valvular disease were unrelated to the ACE genotypes. The present data suggested the irrelevance of ACE gene polymorphism in clinical manifestations in patients with ADPKD.

Genotype↗
PubMed1997

Experimental diabetes upregulates the expression of uretereral endothelin receptors.

We investigated the binding characteristics of endothelin (ET) receptors in the ureters of rats with experimentally induced diabetes and diuresis. Receptor binding experiments demonstrated an upregulation in the expression of [125I]ET-1 binding sites in the diabetic rat ureter but not in the diuretic rat ureter. ET-1, ET-3, IRL 1620, and BQ 610 inhibited [125I]ET-binding to the rat ureter consistent with the predominance of ETA receptors in these tissues. The subtype specificity of ET receptors in ureteral tissues was confirmed with inhibition data obtained from cloned human ETA and ETB receptors.

Animals↗
PubMed1997

Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts.

Signaling pathways mediated by tyrosine phosphorylation and dephosphorylation have been reported to be involved in the regulation of cytoskeletal organization in osteoclasts, the principal cells responsible for bone resorption. We examined the effects of tiludronate [(4-chlorophenyl)thiomethylene bisphosphonate] on the cytoskeleton and the balance of phosphotyrosine levels in osteoclast-like multinucleated cells (OCLs) formed in cocultures of mouse osteoblastic cells and bone marrow cells. When OCLs were placed on plastic dishes in the presence of 10% fetal bovine serum, they formed a ringed structure of F-actin dots (actin ring) within 2 h. Tiludronate did not inhibit the process of actin ring formation, but it disrupted preformed actin rings in a time- and a dose-dependent manner. Western blot analysis using an antiphosphotyrosine antibody revealed that tyrosine phosphorylation of certain proteins in OCLs was stimulated by tiludronate added to the purified OCLs. Tyrosine kinase activity of the p60c-src immunoprecipitated from cell lysates of the purified OCLs was not affected by tiludronate directly added to the kinase assay. OCL lysates stimulated dephosphorylation of tyrosine-phosphorylated substrates such as phosphoneuroprotein 14 and epidermal growth factor receptors. Like sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, tiludronate dose-dependently inhibited tyrosine dephosphorylation of those substrates induced by OCL lysates. These findings suggest that tiludronate disrupts the preformed actin rings and suppresses bone-resorbing activity by inhibiting protein tyrosine phosphatases in osteoclasts.

Actins↗
PubMed1997

Serum pyridinoline crosslinks as markers of tumour-induced bone resorption.

OBJECTIVE: To assess serum pyridinoline (Py) and deoxypyridinoline (dPy), using a new high-performance liquid chromatography (HPLC) method, as a serum marker to determine the incidence of metastatic bone disease in an animal model and in the monitoring of patients with or without metastatic bone disease from prostate cancer and renal cell carcinoma (RCC). PATIENTS, MATERIALS AND METHODS: Female C3H/He mice (8-12 weeks old) received a subcutaneous injection of tumour-cell suspensions of serially transplanted MBT tumours. The tumour cells induced osteolysis associated with osteoclast proliferation and serum samples were evaluated for Py and dPy using HPLC. The growth of the tumour macroscopically and histologically, and the extent of bone loss assessed by radiography, were compared with the serum Py and dPy level. In the clinical study, patients with or without bone metastases from RCC (24 patients) or prostate cancer (37 patients) were monitored using the same techniques and the number and extent of bone metastases compared with serum Py and dPy levels both in these patients and in 84 healthy control subjects. RESULTS: There was a significant correlation between the bone loss evaluated by radiography and the level of serum Py in the animal model. Patients with bone metastases from RCC had higher values of Py and dPy than patients without known metastatic bone disease. The serum Py level increased in two patients as metastatic bone disease progressed. Similarly, in patients with prostate cancer, the mean level of serum Py and dPy was higher in patients with bone metastasis than in the control group, and also higher than that in patients without metastases. The serum Py and dPy levels could also distinguish patients with metastatic bone disease with and without a lytic component. CONCLUSION: Measurements of serum Py appear to provide a good index of increased bone resorption induced by experimental tumours and in patients with bone metastases from RCC and prostate cancer.

Aged↗