Search PubMed⌕ Search

Biomedical subjects

K Yoshioka

Publications and source records attributed to K Yoshioka.

At least 73 records · Page 4Linked to original sources
PubMed2001

Clinical study of vestibular-evoked myogenic potentials and auditory brainstem responses in patients with brainstem lesions.

A total of 13 patients, who were diagnosed with localized brainstem lesions using MRI, were investigated. The diagnoses were multiple sclerosis in five patients, brainstem hemorrhage in three patients, pontomedullary infarction in one patient and Wallenberg's syndrome in four patients. In addition, 42 ears of 21 normal adult volunteers were also examined. In a patient with upper brainstem lesions mainly affecting the midbrain, the auditory brainstem response (ABR) was abnormal but the vestibular-evoked myogenic potential (VEMP) was normal. In four patients with middle brainstem lesions which mainly affected the pons, both ABR and VEMP were abnormal. In five patients with lower brainstem lesions which mainly affected the medulla, the ABR was normal but the VEMP was abnormal. In those patients with middle-to-lower brainstem lesions, a disappearance of VEMP reactions, delay of the positive-negative (PN) wave, increase in PN interpeak latency and decrease in PN amplitude on the affected side were confirmed. In conclusion, the VEMP test comprises a useful new diagnostic method for identifying lower brainstem lesions.

Adolescent↗
PubMed2000

Kaluza-Klein Mediated supersymmetry breaking.

The four-dimensional effective theories with compactified extra dimensions are considered. We there discuss a new framework for communicating supersymmetry breaking to the visible sector where the radius modulus, which determines the size of extra dimensions, has an auxiliary vacuum expectation value. The modulus couplings generate mass splitting in Kaluza-Klein supermultiplets and they act as messengers of supersymmetry breaking. The soft masses are expressed in terms of renormalization-group functions and the sparticle spectrum is determined by what kind of field propagates in the bulk.

Journal Article↗
PubMed2000

A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways.

We previously reported that c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) functions as a putative scaffold factor in the JNK mitogen-activated protein kinase (MAPK) cascades. In that study we also found MEK1 and Raf-1, which are involved in the extracellular signal-regulated kinase (ERK) MAPK cascades, bind to JSAP1. Here we have defined the regions of JSAP1 responsible for the interactions with MEK1 and Raf-1. Both of the binding regions were mapped to the COOH-terminal region (residues 1054-1305) of JSAP1. We next examined the effect of overexpressing JSAP1 on the activation of ERK by phorbol 12-myristate 13-acetate in transfected COS-7 cells and found that JSAP1 inhibits ERK's activation and that the COOH-terminal region of JSAP1 was required for the inhibition. Finally, we investigated the molecular mechanism of JSAP1's inhibitory function and showed that JSAP1 prevents MEK1 phosphorylation and activation by Raf-1, resulting in the suppression of the activation of ERK. Taken together, these results suggest that JSAP1 is involved both in the JNK cascades, as a scaffolding factor, and the ERK cascades, as a suppressor.

Animals↗
PubMed2000

Isoforms of JSAP1 scaffold protein generated through alternative splicing.

We have identified four isoforms of c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1), a scaffold protein that participates in JNK mitogen-activated protein kinase cascades, termed JSAP1a, JSAP1b, JSAP1c, and JSAP1d. The previously identified JSAP1 was renamed JSAP1a to avoid confusion. Analyses of the exon-intron structure of the jsap1 gene indicated that the isoforms are generated through alternative splicing involving exons 5 and 6. The mRNA expression levels of the JSAP1 isoforms differed among the mouse tissues examined. We also investigated the region of JSAP1 responsible for its interaction with JNK, and found that the JNK-binding domain is located between aa residues 201 and 217 in JSAP1a, which is encoded by part of exon 6. As all the JSAP1 isoforms contain this binding domain, we examined the binding affinity of the JSAP1 isoforms for JNK1, JNK2, and JNK3. JSAP1c and JSAP1d, which contain a 31-aa sequence not present in JSAP1a or JSAP1b, had a lower binding affinity for the JNKs, especially JNK3. These results suggest that JSAP1c and JSAP1d may attenuate the scaffolding activity of JSAP1a and/or JSAP1b in JNK cascades, especially the JNK3 cascades.

Adaptor Proteins, Signal Transducing↗
PubMed2000

p300/CBP-dependent and -independent transcriptional interference between NF-kappaB RelA and p53.

p53 and NF-kappaB RelA are activated by various genotoxic agents and mutually suppress each other's ability to activate transcription, most likely through competition for transcriptional coactivators such as CBP or p300. However, we found that the inhibition by RelA of p53 transcriptional activity is not completely restored by CBP/p300 overexpression and that a p53 mutant can not suppress RelA activity despite of its ability to bind CBP/p300. In the present study, we further present evidence that these two transcriptional factors directly interact both in vivo and in vitro. These results therefore indicate that the cross transcriptional interference between p53 and RelA is partly caused by the direct interaction between these two transcription factors which is mediated by their dimerization/tetramerization domains and results in inhibition of each other's transcriptional activity. Finally, cells derived from RelA knockout mice showed enhanced p53 transcriptional activity, suggesting that this cross transcriptional interference is physiologically important in cellular response to genotoxic stress.

Animals↗
PubMed2000

Determination of genes involved in the process of implantation: application of GeneChip to scan 6500 genes.

Using the high-density arrays of oligonucleotides (GeneChip) technology, the expression of uterine genes was examined before and after conceptus implantation in mice. Of the 6500 genes analyzed, levels of 399 gene expressions changed; 192 genes increased levels of expression while the remaining 207 genes declined. The findings suggest that both gene activation and deactivation (suppression) are required for successful implantation.

Animals↗
PubMed2000

Heterogeneous sympathetic innervation influences local myocardial repolarization in normally perfused rabbit hearts.

BACKGROUND: Heterogeneity of sympathetic innervation is thought to contribute to the potential for fatal arrhythmia. However, little is known about the effects of heterogeneous innervation on repolarization. METHODS AND RESULTS: To assess this relationship, we measured activation recovery intervals (ARIs) from 64 epicardial sites in 11 rabbits studied 2 weeks after regional denervation produced by phenol and 4 sham-operated rabbits. ARI results were compared with the distribution of sympathetic innervation measured from 3D reconstructions of serial autoradiographs of [(125)I]metaiodobenzylguanidine and (99m)Tc-sestamibi. ARIs were recorded during baseline sinus rhythm, norepinephrine (NE) infusion (0.1 microg. kg(-1). min(-1)), and left stellate ganglion stimulation (SS). NE shortened ARI in 98% of electrodes in the denervated region. The degree of ARI shortening and dispersion increased (P<0.001 and P<0.01, respectively) as denervation became more severe. SS shortened ARI in 30% of electrodes in the denervated area, with increased shortening and dispersion related to increased severity of denervation (P<0.01). SS prolonged ARI in 70% of electrodes in the denervated area, with no correlation with severity of denervation. CONCLUSIONS: The magnitude and dispersion of local repolarization responses are related to the severity of denervation, as well as the type of stimulation: neural (SS) versus humoral (NE). The differences may relate to the concentration of NE released.

3-Iodobenzylguanidine↗
PubMed2000

Molecular cloning, expression, and chromosomal localization of a human tubulointerstitial nephritis antigen.

Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix basement protein which was originally identified as a target antigen involved in anti-tubular basement membrane (TBM) antibody-mediated interstitial nephritis (TIN). Further investigations elucidated that TIN-ag plays a role in renal tubulogenesis and that TIN-ag is defected in hereditary tubulointerstitial disorder such as juvenile nephronophthisis. We previously isolated and characterized 54 kDa glycoprotein as TIN-ag. cDNA encoding rabbit and mouse TIN-ag has recently been identified. In the present study, the cDNA of the human homologue of TIN-ag was cloned and its nucleotide sequence was determined (Accession No. AB022277; the DDBJ nucleotide sequence database). Deduced amino acid sequence (476 aa) exhibited the presence of a signal peptide (1-18 aa), cysteine residues termed follistatin module, six potential glycosylation sites, and an ATP/GTP-binding site. Homology search revealed approximately 85% homology with both rabbit and mouse TIN-ag, and also some ( approximately 40%) similarity with C. elegans. Human TIN-ag contained a sequence similar to several classes of extracellular matrix molecules in amino terminal region and to cathepsin family of cysteine proteinases in the carboxyl terminal region. Northern blot analysis revealed exclusive expression of this molecule in human adult and fetal kidney tissues. Using a monoclonal antibody recognizing human TIN-ag, protein expression ( approximately 50 kDa) was identified in cultured COS-1 cells transfected with human TIN-ag cDNA. The human TIN-ag was mapped to chromosome 6p11.2-12 by fluorescence in situ hybridization. These results may provide further evidence for understanding TIN-ag molecule and clues for gene analysis of juvenile nephronophthisis.

Adult↗
PubMed2000

Randomized trial of fecal diversion for sphincter repair.

PURPOSE: Fecal diversion for sphincter repair is controversial. This randomized trial assessed whether fecal diversion would improve primary wound healing and functional outcome after sphincter repair. METHODS: Thirty-three patients with fecal incontinence requiring sphincter repair were recruited, but only 27 agreed to be randomly assigned to a defunctioning stoma (n = 13) or no stoma (n = 14). Patients were assessed by the Cleveland Clinic Incontinence Score (0-20) and anal physiology; the mean follow-up was 34 (range, 16-47) months. RESULTS: Incontinence score improved significantly in both groups (stoma, 13.5-7.8; P = 0.0072; no stoma, 14-9.6; P = 0.0470): No difference was found between the two groups. Maximum resting pressure and maximum squeeze pressure increased significantly only in the no-stoma group (maximum resting pressure, 52.4-71.3 cm H2O; maximum squeeze pressure, 87.3-100.7 cm H2O; P < 0.0001). There was no significant difference in functional outcome (stoma, 7.8; no stoma, 9.6; P = 0.4567) or the number with complications of sphincter repair (stoma, 5; no stoma, 3; P = 0.4197). However, stoma-related complications occurred in 7 of 13 patients having a stoma (parastomal hernia, 2; prolapsed stoma, 1; incisional hernia at the stoma site requiring repair, 5; and wound infection at the closure site, 1). CONCLUSION: Fecal diversion in sphincter repair is unnecessary, because it gives no benefit in terms of wound healing or functional outcome, and it is a source of morbidity.

Adult↗
PubMed2000

Overexpression of bcl-2 in transient abnormal myelopoiesis associated with Down syndrome.

Transient abnormal myelopoiesis (TAM) is a haematological complication found in Down syndrome. To determine the mechanisms of sustained proliferation of TAM cells, we studied the expression of apoptosis-related proteins, such as bcl-2, Fas (APO-1/CD95) and p-53, in peripheral blood cells from a new-born infant with Down syndrome and TAM. Using flow cytometry, peripheral blood mononuclear cells (PBMCs), consisting mostly of blast cells, showed marked expression of bcl-2 protein but not of Fas or p-53 products. DNA gel electrophoresis of PBMCs, cultured in the absence of serum factors, revealed no marked fragmentation. Our findings suggest that bcl-2 overexpression may be associated with prolonged cell survival of TAM cells.

Down Syndrome↗
PubMed2000

Small guanosine triphosphatase Rho/Rho-associated kinase as a novel regulator of intracellular redistribution of lysosomes in invasive tumor cells.

To investigate the role of RhoA on the intracellular membrane dynamics of lysosomes in rat hepatoma cells (MM1), we analyzed the localization of lysosomal aspartic proteinase cathepsin D by confocal immunofluorescence microscopy in the dominant active RhoA-transfected cells. Here we show that the transfection of the dominant active form of human small guanosine triphosphatase (GTPase) RhoA in MMI cells, a highly invasive cell line, causes the redistribution and spreading of small punctate structures stained for cathepsin D throughout the cytoplasm. We found that the microtubule organization was markedly different in the two cell lines: uniformly developed and polymerized microtubule filaments were seen in the mock transfectants; however, the dynamic organization of microtubules was less pronounced in the active RhoA transfectants. Furthermore, we found for the first time that a selective inhibitor of Rho-associated kinase (p160ROCK), Y-27632, impeded the subcellular spreading of cathepsin D staining and promoted reclustering of cathepsin D toward the perinuclear region in the active RhoA-transfected cells. To our knowledge, this is the first indication that the RhoA/ROCK-mediated signaling pathway is involved in the intracellular membrane dynamics of lysosomes by regulating the cytoskeletal microtubule organization as well as the actin cytoskeletons.

Actins↗
PubMed2000

Clinical and radiological features in four adolescents with nutcracker syndrome.

We describe four adolescents with the nutcracker syndrome. In three patients, the nutcracker syndrome was detected through mass urinary screening; the other patient was diagnosed after a sudden onset of dark urine. All patients underwent magnetic resonance angiography (MRA) for diagnosis of the nutcracker syndrome, which revealed dilatation of the left renal vein ranging between 7.4 and 13 mm at the hilar portion. A renal biopsy, performed in three patients, showed no remarkable abnormalities in the glomerulus or tubulointerstitial tissue. The patients complained of physical discomfort, including headache, abdominal pain, fainting, and tachycardia mimicking clinical symptoms of an orthostatic disturbance. However, no chronic systemic diseases were detected in any of the patients after repeated laboratory examinations. An orthostatic disturbance preceded diagnosis in three patients. This report indicates that the nutcracker syndrome may cause serious physical ailments that clinically mimic an orthostatic disturbance. It may be important to identify the nutcracker syndrome among children who manifest non-specific physical complaints. MRA could be a safe and reliable method for diagnosing the nutcracker syndrome.

Abdominal Pain↗
PubMed2000

Characteristics of monocarboxylates as energy substrates other than glucose in rat brain slices and the effect of selective glial poisoning - a 31P NMR study.

In rat brain slices we examined the differences in the levels of high-energy phosphates in the presence of various energy substrates by using 31P NMR with a time resolution of 4 min at 25 degrees C. In parallel experiments we recorded population excitatory postsynaptic potentials (EPSPs) from granule cells in rat hippocampal slices. During high K(+) stimulation (8 min) phosphocreatine (PCr) decreased to a low level and recovered to the control level in standard artificial cerebrospinal fluid (ACSF) in about 10 min. Population EPSPs disappeared following high-K(+) stimulation and recovered in standard ACSF. In iodoacetic acid (IAA)-pretreated slices, whereas glucose was unable to support energy metabolism, the PCr level, which decreased following high-K(+) stimulation, recovered in ACSF containing lactate or pyruvate. The half-time of recovery of PCr levels in ACSF containing lactate was longer than that containing glucose. Population EPSPs in standard ACSF were maintained for more than 1 h, but those in ACSF containing lactate decreased gradually by about half in 40 min. In IAA-pretreated slices, when further treated with fluorocitrate (100 microM) for 2 h, the recovery of the PCr level in ACSF containing lactate after high-K(+) stimulation was completely abolished, whereas the recovery of the PCr level in ACSF containing pyruvate was unaffected. These results indicate that neurons can utilize pyruvate as well as glucose, but not lactate, as exogenous energy substrates, and that lactate may be metabolized to pyruvate in glial cells and transported to neurons to be utilized as an energy substrate.

Animals↗
PubMed2000

Clinical efficacy of insulin-like growth factor-1 in a patient with autoantibodies to insulin receptors: a case report.

The type B insulin-resistance syndrome is characterized by the presence of anti-insulin receptor antibodies that cause severe insulin resistance. Treatments including steroids, cyclophosphamide, plasmapheresis, or insulin-like growth factor-1 (IGF-1) are chosen according to severity of insulin resistance. We describe a patient with type B insulin resistance syndrome who was treated successfully with human recombinant (hr) IGF-1, although this treatment provoked a severe allergic reaction. An elderly man with impaired glucose tolerance and unpredictable hypoglycemic episodes which were gradually worsening increased in hemoglobin (Hb)A1c concentration from 6.5 to 13.4%. His fasting and postprandial hyperglycemia were associated with severe hyperinsulinemia. The patient was diagnosed with type B insulin-resistance syndrome by the presence of anti-insulin receptor antibodies. Double-filtration plasmapheresis, plasma exchange, and immunosuppressive therapy with cyclophosphamide and cyclosporin all failed to suppress anti-insulin receptor antibodies more than transiently. When we attempted the treatment by daily administration of hrIGF-1, fasting and postprandial plasma glucose concentrations became normal and HbA1c levels decreased to 7.1% over 2 months, until on one occasion administration resulted in anaphylaxis. After the patient became stable, desensitization therapy was performed successfully, and hrIGF-1 could be administered again with the plasma glucose returning. We concluded that IGF-1 therapy was an effective treatment choice for type B insulin-resistance syndrome in cases whose plasma exchange and immunosuppressive therapy have failed.

Aged↗
PubMed2000

A simple method using 31P-NMR spectroscopy for the study of protein phosphorylation.

Nonradioactive 31P-NMR spectroscopy has previously been used for the study of protein phosphorylations. However, the procedures does not seem to be easy for non-experts of this field, hence, this approach has not been widely used. We introduce here a simple protocol with 31P-NMR spectroscopy to study in vitro phosphorylation in receptor proteins. The effectiveness of this method was verified using synthetic peptides and recombinant proteins of the C-terminus of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor, whose phosphorylations are considered to have important roles in synaptic plasticity. We show that a decrease in the pH of the sample solution after the phosphorylation reaction is critical for the separation of the phosphorylation signals. In the analysis of the C-terminal portion of the GluR2 AMPA receptor, the phosphorylation sites of which had not hitherto been well clarified, we found the presence of at least three protein kinase C (PKC) phosphorylation sites. Furthermore, this method allows prediction of the origins of each of the phosphorylation peaks. Thus, the techniques we described here is useful for examination of protein phosphorylation and permits us to safely conduct repetitive experiments.

Amino Acid Sequence↗
PubMed2000

Randomized controlled trial of twice-a-day administration of natural interferon beta for chronic hepatitis C.

We conducted a randomized controlled trial to assess the efficacy of twice-a-day administration of natural interferon beta (IFNbeta) as an induction of IFN therapy for chronic hepatitis C. Seventy-one patients with chronic hepatitis C were enrolled into the trial and randomly assigned into three treatment groups. Six million units (MU) of IFNbeta were administered once-a-day for the first 4 weeks, and then thrice weekly for 12 weeks in 20 patients (once-a-day group). Three milion units of IFNbeta were administered twice-a-day for the first 2 weeks, 6 MU once-a-day for the next 2 weeks, and then thrice weekly for 12 weeks in 23 patients (twice-a-day+beta group), or 6 MU of lymphoblastoid IFNalpha were administered thrice weekly for the last 12 weeks instead of IFNbeta in 28 patients (twice-a-day+alpha group). Four patients in once-a-day group (20%), 9 in twice-a-day+beta group (39%), and 12 in twice-a-day+alpha group (43%) obtained sustained response. Sustained response rate in twice-a-day groups was higher than in once-a-day group, although there was no statistical significance. The present study suggested the possible superiority of twice-a-day administration of IFNbeta as an induction therapy to once-a-day administration, but further studies are needed to confirm this regimen.

Journal Article↗
PubMed2000

Combined phlebotomy and ursodeoxycholic acid treatment in the patients with chronic hepatitis C.

As an option to interferon, either iron removal by phlebotomy or ursodeoxycholic acid administration has been recommended for patients with chronic hepatitis C. Some patients, however, show only partial responses to such monotherapy. In the present study, we investigated the effects of a combination of phlebotomy and ursodeoxycholic acid in the patients who did not show normalization of serum alanine aminotransferase levels by either phlebotomy or ursodeoxycholic acid monotherapy. The combination of these therapies in any order additively improved the biochemical parameter to the upper normal range. There were no statistically significant differences between the results of the two combination treatments. The combination treatment was also effective in decreasing serum alpha fetoprotein levels.

Journal Article↗