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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 19 recordsLinked to original sources
PubMed2006

Suppression of myofibrillar proteolysis in chick skeletal muscles by alpha-ketoisocaproate.

We previously reported that L-leucine suppresses myofibrillar proteolysis in chick skeletal muscles. In the current study, we compared the effects of L- and D-enantiomers of leucine on myofibrillar proteolysis in skeletal muscle of chicks. We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate (alpha-KIC), mediates the effects of leucine. Food-deprived (24 h) chicks were orally administered 225 mg/100 g body weight L-leucine, D-leucine or alpha-KIC and were sacrificed after 2 h. L-Leucine administration had an obvious inhibitory effect on myofibrillar proteolysis (plasma N(tau)-methylhistidine concentration) in chicks while D-leucine and alpha-KIC were much more effective. We also examined the expression of the proteolytic-related genes (ubiquitin, proteasome, m-calpain and cathepsin B) by real-time PCR of cDNA in chick skeletal muscles. Ubiquitin mRNA expression was decreased by D-leucine and alpha-KIC but not L-leucine. Proteasome and m-calpain mRNA expressions as well as cathepsin B mRNA expression were likewise decreased by L-leucine, D-leucine and alpha-KIC. These results indicate that D-leucine and alpha-KIC suppress proteolytic-related genes, resulting in an decrease in myofibrillar proteolysis while L-leucine is much less effective in skeletal muscle of chicks, may be explain by conversion of D-leucine to alpha-KIC.

Animals↗
PubMed2006

Usefulness of three-dimensional full-scale modeling of surgery for a giant cell tumor of the cervical spine.

STUDY DESIGN: Case report. OBJECTIVES: To report a case with giant cell tumor (GCT) of C6 vertebra, in which three-dimensional (3-D) full-scale modeling of the cervical spine was useful for preoperative planning and intraoperative navigation. SETTING: A university hospital in Japan. CASE REPORT: A 27-year-old man with a GCT involving the C6 vertebra presented with severe neck pain. The C6 vertebra was collapsed and the tumor had infiltrated around both vertebral arteries (VAs). A single-stage operation combining anterior and posterior surgical procedures was scheduled to resect the tumor and stabilize the spine. To evaluate the anatomic structures within the surgical fields, we produced a 3-D full-scale model from the computed tomography angiography data. The 3-D full-scale model clearly showed the relationships between the destroyed C6 vertebra and the deviations in the courses of both VAs. Using the model, we were able to identify the anatomic landmarks around the VAs during anterior surgery and to successfully resect the tumor. During the posterior surgery, we were able to determine accurate starting points for the pedicle screws. Anterior iliac bone graft from C5 to C7 and posterior fixation with a rod and screw system from C4 to T2 were performed without any complications. Postoperatively, the patient experienced relief of his neck pain. CONCLUSION: The 3-D full-scale model was useful for simultaneously evaluating the destruction of the vertebral bony structures and the deviations in the courses of the VAs during surgery for GCT involving the cervical spine.

Adult↗
PubMed2006

Transient paraparesis after laminectomy for thoracic ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum.

STUDY DESIGN: Case report. OBJECTIVES: To report a case with thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF), in which postoperative paralysis occurred after laminectomy and was reversed after an additional posterior instrumented fusion. SETTING: A University Hospital in Japan. CASE REPORT: A 71-year-old woman, with a spastic palsy of both lower extremities, had OPLL and OLF at T10-T11, which pinched the spinal cord anteriorly and posteriorly. She underwent a laminectomy at T10-T11, and no further neurological deterioration was seen immediately after surgery. Over the next 18 h, however, myelopathy worsened, showing severe paraparesis. An additional posterior instrumented fusion at T7-L1 was performed without correction of the kyphosis. After fusion, neurological deficits gradually recovered, despite the presence of residual anterior impingement of spinal cord by the OPLL. CONCLUSIONS: The present case provides evidence for the possibility that laminectomy alone produces postoperative paralysis for combined thoracic OPLL and OLF, and we recommend that a posterior instrumented fusion should be added when posterior decompression is performed for this disorder.

Female↗
PubMed2006

Optic nerve and spinal cord manifestations of malignant atrophic papulosis (Degos disease).

A fatal case of malignant atrophic papulosis (Degos disease) with optic nerve and spinal cord involvement is described. Magnetic resonance imaging (MRI) of the optic nerve showed abnormal signal enhancement on fat suppressed T1 weighted images after intravenous meglumine gadopentetate infusion. On T2 weighted sagittal images, a sawtooth pattern was observed over seven vertebral segments of the spinal cord. On necropsy, a severe loss of myelinated nerve fibres in the left optic nerve was seen, with thrombotic obstruction of the central retinal artery. Spongy degeneration was observed in all levels of the spinal cord, with patchy and motheaten patterns caused by thromboses and endothelial proliferation in subarachnoid vessels. Findings on MRI were consistent with findings on pathological examination.

Atrophy↗
PubMed2006

Prognostic factors of primary biliary cirrhosis detected by health screening.

AIM: The liver cirrhosis is likely to differ in the Japanese and Western populations. Thus, we performed a retrospective cohort analysis by a review of clinical records to clarify prognostic factors after the onset of primary biliary cirrhosis (PBC) detected by health screening. METHODS: The subjects were 52 patients with PBC. Thirty-nine factors were evaluated concerning clinical data and extracted prognostic factors using the Cox proportional hazard model. RESULTS: The mean duration of the follow-up period was 5.1 years, during which 6 (11.5%) of the patients died. The cumulative survival rate after the onset of PBC was 93.4% after 5 year, and 67.8% after 10 years. Multivariate analysis indicated 2 factors, i.e. the body mass index (BMI), and IgG, as independent prognostic factors. Their hazard ratios were 0.399 (per 1 kg/m2 of BMI) and 1.282 (per 100 mg/dL of IgG). The prognostic index (PI) was calculated by the following formula using these 2 factors. PI = 0.919 x BMI+0.249 x IgG. CONCLUSIONS: The prediction of the outcome using PI based on the 2 factors provides additional information for the determination of the therapeutic approach in PBC after health screening.

Cohort Studies↗
PubMed2005

Dynamic gadolinium-enhanced fat-suppressed T1-weighted MRI (chemical shift selective images) for remitting seronegative symmetrical synovitis with pitting edema.

A 75-year-old man suddenly suffered from polyarthralgia and pitting edema in his distal extremities. Laboratory tests revealed inflammation, negative rheumatoid factor, and positive B7 human leukocyte antigen typing. Severe synovitis was observed in dynamic gadolinium-enhanced fat-suppressed (DGEFS) T1-weighted images of his right hand. Our diagnosis was remitting seronegative symmetrical synovitis with pitting edema (RS(3)PE syndrome). He responded dramatically to low-dose corticosteroids, after which his synovitis remarkably improved as observed with DGEFS imaging. DGEFS imaging is useful for distribution of synovitis in patients with RS(3)PE syndrome as well as assessing the efficacy of treatment.

Aged↗
PubMed2005

Temporal changes in postural sway caused by ultrashort-acting hypnotics: triazolam and zolpidem.

Two ultrashort-acting hypnotics, triazolam 0.25 mg and zolpidem 10 mg, were studied for their effects on equilibrium function in humans. Eight healthy male subjects participated in a double-blind, placebo-controlled study after informed consent. They subjected to static equilibrium tests, oculomotor tests and an assay of drug concentrations in the blood. Zolpidem was statistically significant in postural sway in tandem stance test, as defined by parametric values of tracing sum length and polygonal area of foot pressure center measured by a gait analysis system. In the tandem stance test, triazolam was statistically significant in postural sway only as defined by the polygonal area. However, in the Romberg test, the only statistically significant difference in zolpidem use was observed in polygonal area values. Blood concentrations of triazolam and zolpidem were found to closely correlate with the extent of postural sway in both tandem stance and Romberg tests. In this study, zolpidem with minimal muscle-relaxant effect incurred imbalance more extensively than triazolam, which is known for its effect of muscle relaxation. In addition, gaze deviation nystagmus was observed only in zolpidem use in 5 of 8 subjects (62.5%). From these results, it is suggested that in the use of hypnotics, sway derives from the suppression of the central nervous system relevant to awakening rather than from muscle relaxation. The prior reference to blood concentrations of hypnotics should help improve safety care in minimizing loss of balance control and possible fall.

Accidental Falls↗
PubMed2005

Anoxic depolarization of rat hippocampal slices is prevented by thiopental but not by propofol or isoflurane.

BACKGROUND: There is strong evidence to suggest that anoxic depolarization (AD) is an important factor in hypoxia/ischaemia-induced neural damage. Treatments that prevent the occurrence of AD may be useful in providing neuronal protection against hypoxia. The current study was designed to determine whether general anaesthetics which have been suggested to 'induce prophylaxis' against hypoxia can attenuate the incidence of AD. METHODS: The effects of anoxia (3 min) on evoked extracellularly recorded field potentials of CA1 neurons in rat hippocampal slices were assessed in the absence and presence of the i.v. general anaesthetics thiopental and propofol and the volatile anaesthetic isoflurane. RESULTS: In the absence of anaesthetics, AD occurred in 81% of the preparations tested. Thiopental (2 x 10(-4) M) significantly reduced the incidence of AD (16%, P=0.0006). In comparison, propofol (2 x 10(-4) M) and isoflurane (1.5 vol%) were ineffective (69% and 60%, respectively). Furthermore, in the presence of thiopental, the population spike amplitude recovered with and without AD (90% and 94% of pre-anoxic value, respectively) following 3 min anoxia. CONCLUSION: The prophylactic effect of thiopental against hypoxia might be induced, in part, by preventing the generation of AD.

Anesthetics, Inhalation↗
PubMed2005

Effects of fibrates on human organic anion-transporting polypeptide 1B1-, multidrug resistance protein 2- and P-glycoprotein-mediated transport.

The effects of different fibric acid derivatives (bezafibrate, clofibrate, clofibric acid, fenofibrate, fenofibric acid and gemfibrozil) on human organic anion transporting-polypeptide 1B1 (OATP2, OATP-C, SLC21A6), multidrug resistance protein 2 (MRP2/ABCC2) and MDR1-type P-glycoprotein (P-gp/ABCB1) were examined in vitro. Cyclosporin A (a known inhibitor of OATP1B1 and P-gp), MK-571 (a known inhibitor of MRP2) and cimetidine (an organic cation) were also tested. Bezafibrate, fenofibrate, fenofibric acid and gemfibrozil showed concentration-dependent inhibition of estradiol 17-beta-D-glucuronide uptake by OATP1B1-stably transfected HEK cells, whereas clofibrate and clofibric acid did not show any significant effects up to 100 microM. Inhibition kinetics of gemfibrozil, which exhibited the most significant inhibition on OATP1B1, was shown to be competitive with a Ki = 12.5 microM. None of the fibrates showed any significant inhibition of MRP2-mediated transport, which was evaluated by measuring the uptake of ethacrynic acid glutathione into MRP2-expressing Sf9 membrane vesicles. Only fenofibrate showed moderate P-gp inhibition as assessed by measuring cellular accumulation of vinblastine in a P-gp overexpressing cell-line. Cyclosporin A significantly inhibited OATP1B1 and P-gp, whereas only moderate inhibition was observed on MRP2. The rank order of inhibitory potency of MK-571 was determined as OATP1B1 (IC50: 0.3 microM) > MRP2 (4 microM) > P-gp (25 microM). Cimetidine did not show any effects on these transporters. In conclusion, neither MRP2- nor P-gp-mediated transport is inhibited significantly by the fibrates tested. Considering the plasma protein binding and IC50 values for OATP1B1, only gemfibrozil appeared to have a potential to cause drug-drug interactions by inhibiting OATP1B1 at clinically relevant concentrations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein-Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sjögren's syndrome patients with pulmonary involvements.

Associations of Epstein-Barr virus (EBV) and autoimmune diseases have been hypothesized. We have analysed IgG antibodies to EBV nuclear antigen (EBNA)-2 in sera from Japanese patients with autoimmune systemic connective tissue diseases (CTD), exemplified by systemic lupus erythematosus (SLE), primary Sjogren's syndrome (SS), rheumatoid arthritis (RA), systemic sclerosis (SSc) and secondary SS (classical CTDs complicated with SS). An enzyme-linked immunosorbent assay (ELISA) which uses glutathione-S-transferase polypeptides fused to EBV nuclear antigen (EBNA)-2 and EBNA-1 was developed. Ratios of IgG antibody reactivity to whole IgG concentrations of sera were calculated to normalize EBNA-2 and EBNA-1 antibody levels to the hypergammaglobulinaemia that occurs in CTD. The ELISA optical density OD(450) readings of IgG antibodies to both the amino-terminal aa 1-116 of EBNA-2 and carboxyl-terminal aa 451-641 of EBNA-1 were elevated significantly in patients with SLE, primary SS, RA, SSc and secondary SS when compared to EBNA-1. The OD readings were divided by serum IgG concentrations to normalize for the hypergammaglobulinaemia. The specific levels of IgG antibodies to the amino-terminal region of EBNA-2 were elevated in patients with SLE, primary SS or RA, as well as those with secondary SS complicated with SLE or RA. The EBNA-2 amino-terminal region contains a polyproline tract and a proline-rich sequence and has considerable amino acid sequence homology with many cellular proline-rich proteins. High ratios of EBNA-2 aa 1-116 to EBNA-1 aa 451-641 IgG antibody levels which probably suggest reactivation of EBV latent infection were associated significantly with pulmonary involvement in SS patients. These results are consistent with the hypothesis that the sequence similarity between the amino-terminal region of EBNA-2 and proline-rich cellular proteins is associated with pathogenesis in a subpopulation of CTD patients, possibly by the molecular mimicry-epitope shift mechanism.

Adult↗
PubMed2005

Selective inducible nitric oxide synthase inhibition attenuates organ dysfunction and elevated endothelin levels in LPS-induced DIC model rats.

We examined the role of nitric oxide (NO) produced by an inducible isoform of NO synthase (iNOS) using N[6]-(iminoethyl)-lysine (L-NIL), a selective iNOS inhibitor, in the rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) and investigated changes in organ function, plasma levels of NOX (metabolites of NO) and endothelin. We induced experimental DIC by the sustained infusion of 30 mg kg(-1) LPS for 4 h via the tail vein. We then investigated the effect of L-NIL (6 mg kg(-1), from - 0.5 to 4 h) on LPS-induced DIC. Blood was withdrawn at 4 and 8 h, and all four groups (LPS with or without L-NIL at 4 and 8 h) consisted of eight rats. Three of the animals in the 8-h LPS group died, and we examined blood samples from five rats in this group. None of the other rats died. The LPS-induced elevation of creatinine, alanine aminotransferase, glomerular fibrin deposition and plasminogen activator inhibitor was significantly suppressed by L-NIL coadministration, although L-NIL did not affect the platelet count, fibrinogen concentration or the level of thrombin-antithrombin complex. Moreover, plasma levels of the D-dimer that reflect the lysis of cross-linked fibrin were significantly increased by L-NIL coadministration in the LPS-induced DIC model. Plasma levels of NOX and endothelin were obviously increased by LPS infusion. However, both levels were significantly suppressed in the LPS + L-NIL group, when compared with the LPS group. Although mean arterial pressure (MAP) was significantly decreased between 2 and 8 h compared with the control in the LPS group, this depression was significantly attenuated in the LPS + L-NIL group. Our results suggest that NO induced by iNOS contributes to hypotension (depressed MAP), the progression of hepatic and renal dysfunction, microthrombus deposition and elevated endothelin levels in the rat model of LPS-induced DIC.

Alanine Transaminase↗
PubMed2004

Reduced inflammatory pain in mice deficient in the differential screening-selected gene aberrative in neuroblastoma.

Differential screening-selected gene aberrative in neuroblastoma (Dan) protein is produced in small neurons of dorsal root ganglia. Thermal and mechanical allodynia and Fos expression in the spinal dorsal horn evoked by inflammation and neuropathic pain were investigated using Dan-deficient mice. Mice showed pain reactions induced by the introduction of complete Freund's adjuvant (CFA) into their hind paw (inflammatory pain model) and after sciatic nerve ligation (neuropathic pain model). In the inflammatory pain model, thermal and mechanical pain thresholds in Dan-deficient mice were significantly higher than those of wild-type mice. The number of Fos-immunoreactive cells in the dorsal horn during the inflammatory period was significantly less in Dan-deficient mice. However, in the neuropathic pain model, no differences in thermal hypersensitivity, mechanical allodynia, or the number of Fos-immunoreactive cells in the dorsal horn were observed between the mice. These data suggest that Dan may be a neuromodulator in inflammatory pain.

Animals↗
PubMed2004

Implication of spinal protein kinase C in the suppression of morphine-induced rewarding effect under a neuropathic pain-like state in mice.

We previously demonstrated that spinal protein kinase C (PKC) is involved in the development of a neuropathic pain-like state induced by sciatic nerve ligation, and the morphine-induced rewarding effect is attenuated by sciatic nerve ligation in rodents. Here we first investigated whether sciatic nerve injury could change the activity of a conventional PKC (cPKC) and an atypical PKC isoform PKCzeta in the mouse spinal cord. The second experiment was to investigate whether direct inhibition of spinal PKC by intrathecal (i.t.) administration of a specific PKC inhibitor, 2-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl]-3-(1-methyl-1H-indole-3-yl)maleimide (RO-32-0432), could affect the rewarding effect induced by morphine following sciatic nerve ligation in mice. We found here that the activities of both cPKC and PKCzeta in the spinal cord were clearly increased following sciatic nerve ligation. Furthermore, i.t. administration of RO-32-0432 reversed a long-lasting pain-like syndrome as indicated by thermal hyperalgesia following sciatic nerve ligation in mice. These data provide direct evidence that activated cPKC and PKCzeta in the spinal cord may contribute to the development and maintenance of neuropathic pain. In the present study, we confirmed that the morphine-induced place preference was significantly suppressed by sciatic nerve ligation. It should be mentioned that i.t. pretreatment with RO-32-0432 significantly reversed the attenuation of morphine-induced rewarding effect following sciatic nerve ligation. These results suggest that activation of PKCs, including cPKC and PKCzeta, within the spinal cord is directly responsible for the attenuation of the morphine-induced rewarding effect under a neuropathic pain-like state following sciatic nerve ligation in mice.

Analgesics, Opioid↗
PubMed2004

Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes.

Intestinal epithelial cell (IEC)-derived cytokines, such as stem cell factor (SCF), interleukin (IL)-7 and IL-15 are known to be required for the development of intestinal intraepithelial lymphocytes (IELs). A newly described cytokine, IL-18, has also been shown to be produced by intestinal epithelial cells. To demonstrate the functional effects of IL-18 on human IELs, we assessed IL-18/IL-18 receptor expression in IEC/IEL and proliferation following stimulation of intestinal IELs by IL-18. IL-18 transcripts were detected both in freshly isolated human colonic epithelial cells and in various colonic epithelial cell lines. IL-18 protein was also detected by ELISA and flow cytometric analysis using antihuman IL-18-specific monoclonal antibody (MoAb). Furthermore, IELs constitutively expressed the IL-18 receptor in addition to the IL-2 and IL-7 receptors. More importantly, IL-18 augmented significant proliferative responses of IEL in combination with IL-2, IL-7 and IL-15 both in the presence and in absence of anti-CD3 MoAb. These results suggest that IL-18 might play a crucial role in the proliferation and maintenance of intestinal IELs.

Antibodies, Monoclonal↗
PubMed2004

Ghrelin-induced growth hormone release from isolated rat anterior pituitary cells depends on intracellullar and extracellular Ca2+ sources.

Ghrelin, a novel growth hormone (GH)-releasing peptide, was isolated from the rat stomach as an endogenous ligand to the growth hormone secretagogues receptor. It is known that ghrelin stimulates the release of GH from the rat anterior pituitary gland, but the intracellular signal cascade in somatotrophs has not yet been clarified. In this study, using an isolated cell perifusion system, we examined whether ghrelin- and growth hormone-releasing hormone (GHRH)-induced GH secretion from rat pituitary cells depends on intra- and extracellular Ca(2+) and voltage-gated Ca(2+) channels. For this purpose, we first measured ghrelin- or GHRH-stimulated GH concentration following treatment with reduced extracellular Ca(2+) and/or thapsigargin, an endoplasmic reticulum Ca(2+) ATPase inhibitor. Reductions in the extracellular Ca(2+) concentration to 0.25 mM and to 0 mM resulted in decreases in ghrelin-stimulated GH secretion to 81% and 39% and decreases in GHRH-induced GH secretion to 83% and 13%, respectively, compared to the levels in the case of 2.5 mM Ca(2+) concentration, suggesting that extracellular Ca(2+) is essential for both ghrelin- and GHRH-induced GH secretion. Pretreatment with thapsigargin resulted in a reduction in ghrelin-induced GH secretion to approximately 60% of the control level, but GHRH treatment had not effect on the GH secretion. Moreover, preincubation with thapsigargin and 0 mM extracellular Ca(2+) concentration resulted in significant inhibition of GHRH- and ghrelin-induced GH secretion. Subsequently, to determine whether ghrelin-stimulated GH secretion was induced through voltage-gated Ca(2+) channels, we measured the ghrelin-stimulated GH concentration following treatment with nifedipine, an L-type Ca(2+) channel inhibitor, and found that the amount of GH secretion was reduced to 44% of the control level. Furthermore, by replacement of extracellular Na(2+) in the medium with N-methyl-D(-)-glucamine, an impermeable molecule, GH secretion was reduced to 47%. In this study, we demonstrated that the GH-stimulatory effect of ghrelin, unlike that of GHRH, is achieved through both intracellular and extracellular Ca(2+) sources and that ghrelin-induced extracellular Ca(2+) influx involves an L-type voltage-gated Ca(2+) channel and Na(+) influx.

Animals↗
PubMed2004

Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy.

OBJECTIVE: Progressive supranuclear palsy (PSP) is often misdiagnosed in early phase. The purpose of this study is to investigate the feature of [(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography images for the early diagnosis of PSP. METHODS: We studied 15 patients with PSP and 16 normal subjects. Using SPM99 and analysis of covariance to eliminate the effect of aging, the differences between PSP and normals were displayed as a statistical map. In the PSP, we also investigated the correlation with duration and with the subscores of Unified Parkinson's Disease Rating Scale. RESULTS: The glucose metabolism of midbrain was significantly lower in PSP than in normals. However, correlation was not found between the metabolism of midbrain and clinical deterioration. CONCLUSIONS: The statistical map clearly demonstrated the hypometabolism of midbrain in PSP, which is independent of the clinical deterioration. The hypometabolism of midbrain is one of the most promising sign for early diagnosis of PSP.

Adult↗