Biomedical subjects

K Higashino

Publications and source records attributed to K Higashino.

At least 19 recordsLinked to original sources

PubMed2006

Preservation of C7 spinous process does not influence the long-term outcome after laminoplasty for cervical spondylotic myelopathy.

Axial pain is one of the major complications after laminoplasty, and preservation of C7 spinous process during the procedure can reduce the axial pain. However, it has not been elucidated whether laminoplasty preserving the C7 spinous process can maintain neurological improvement for a long time. The purpose of our retrospective study was to investigate the long-term neurological outcome after open-door laminoplasty preserving the C7 spinous process for cervical spondylotic myelopathy (CSM). Clinical and radiological outcomes were analysed in 42 patients who underwent open-door laminoplasty preserving C7 spinous process and followed up for more than 5 years. Neurological function was evaluated by means of the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy. Axial pain was assessed using a visual analog scale (VAS) at the last examination. Alignment and motion of the cervical spine were measured from radiographs, and magnetic resonance imaging (MRI) was used to evaluate postoperative compression at C7. The mean JOA score was 9.4 before surgery and 12.0 at the latest follow-up. The mean VAS score in 26 patients score was 9.7/100. No compression of the spinal cord was observed in any MRI at the latest follow-up. Preservation of the C7 spinous process does not influence the long-term outcome of CSM after laminoplasty. Although we did not have a comparative group, the procedure described here should be considered as the solution.

Adult↗

PubMed2006

The alpha2 type IX collagen tryptophan polymorphism is associated with the severity of disc degeneration in younger patients with herniated nucleus pulposus of the lumbar spine.

Tryptophan alleles in COL9A2 (Trp2) and COL9A3 (Trp3) have been linked to lumbar disc diseases in the Finnish population. Although such diseases consist of various pathogenetically different conditions, detailed analysis of each has not been well documented. The aim of this study was to clarify whether the collagen IX tryptophan alleles influence the symptomatic degeneration of the lumbar disc in Japanese patients with herniated nucleus pulposus. We performed a prospective study of 84 patients who underwent lumbar discectomy. The degree of disc degeneration was evaluated by magnetic resonance images in relation to the collagen IX genotype. Twenty patients (21.4%) had the Trp2 allele and no patients had the Trp3 allele. Patients under 40 years with the Trp2 allele showed more severe disc degeneration at the surgical level than did those without the Trp2 allele (odds ratio 6.00, P=0.043). In contrast, patients aged 40 years or over did not show significant association between disc degeneration and collagen IX genotype. Our results suggest that the Trp2 allele is an age-dependent risk factor for the severity of disc degeneration in younger patients with symptomatic herniated nucleus pulposus of the lumbar spine.

Adult↗

PubMed2006

Extruded lumbar osseous endplate causing long-term radiculopathy in an adult: an endoscopic excision.

In this report, we described an adult case that had a long-term radiculopathy due to an extruded osseous endplate of the lumbar spine at the L5-S1 intervertebral disc level. The osseous material inside the extruded material was not absorbed, and it had continued compressing the nerve root for one year. Endoscopically, the bony fragment was successfully removed. After the surgery, the patient's symptom disappeared, and neurological deficits became normalized. In conclusion, we propose that surgical intervention should be taken into account for the treatment of HNP, when the extruded material contains bony fragment such as osseous endplate.

Adult↗

PubMed2006

A new method of diagnosing gastric intestinal metaplasia: narrow-band imaging with magnifying endoscopy.

BACKGROUND AND STUDY AIMS: With endoscopy, there is a high rate of interobserver variability in the identification of gastric intestinal metaplasia, and the endoscopic findings correlate poorly with the histological findings. Previous studies by our group investigating the use of a narrow-band imaging system with magnifying endoscopy (NBI-ME) in the gastric mucosa suggested that the appearance of a light blue crest (LBC) on the epithelial surface may be a distinctive endoscopic finding associated with the presence of intestinal metaplasia. The aim of the present study was to clarify the value of NBI-ME for diagnosing gastric intestinal metaplasia. PATIENTS AND METHODS: The LBC was defined as a fine, blue-white line on the crests of the epithelial surface/gyri. To investigate the histology underlying the appearance of LBC, 44 biopsy specimens were obtained from regions containing LBC and 44 from non-LBC mucosa in 34 patients with atrophic gastritis. Three endoscopists then carried out NBI-ME in 107 consecutive patients to validate the diagnostic accuracy of the novel endoscopic technique. The degree of correlation between the LBC grading and the histological parameters of intestinal metaplasia was then assessed. RESULTS: The LBC grading correlated with cells that were positive for CD10 ( P = 0.0001) and Alcian blue ( P = 0.036). The appearance of LBC correlated with histological evidence of intestinal metaplasia with a sensitivity of 89 % (95 % CI, 83 - 96 %), a specificity of 93 % (95 % CI, 88 - 97 %), a positive predictive value of 91 % (95 % CI, 85 - 96 %), a negative predictive value of 92 % (95 % CI, 87 - 97 %), and an accuracy of 91 % (95 % CI, 88 - 95 %). CONCLUSIONS: In narrow-band imaging with magnifying endoscopy, observation of a light blue crest on the epithelial surface in the gastric mucosa is a highly accurate sign of the presence of histological intestinal metaplasia.

Adult↗

PubMed2004

Hypoacidity combined with high gastric juice nitrite induced by Helicobacter pylori infection is associated with gastric cancer.

BACKGROUND: In patients with Helicobacter pylori infection, the concentration of nitrite in gastric juice is elevated. The degree of elevation correlates with that of inflammation and H. pylori density. AIM: The aim of this study was to examine hypoacidity and high nitrite levels related to H. pylori infection in patients with gastric cancer. METHODS: We studied 88 patients with more than one history of endoscopic mucosal resection (EMR) for early gastric cancer and 88 age-matched controls. Concentration of nitrite in gastric juice was measured by Griess reaction, and serum pepsinogen levels were measured by RIA. RESULTS: Multiple malignant lesions were found in 20 of the 88 patients. Serum gastrin, gastric juice pH and nitrite levels in patients with gastric cancer were significantly higher and pepsinogen I and pepsinogen I/II significantly lower than in control subjects. Pepsinogen I level and I/II ratio were lower and gastric juice pH was higher in the protruded-type group than in the depressed-type group. Pepsinogen I and pepsinogen I/II were lower and gastric juice pH was higher in multiple than in single cases. CONCLUSIONS: Hypoacidity combined with high gastric juice nitrite induced by H. pylori infection is associated with the intestinal type of gastric cancer, especially protruded lesions.

Aged↗

PubMed2003

Transient hydrops fetalis of the donor fetus in twin-twin transfusion syndrome after therapeutic amnioreduction.

We present a case of twin-twin transfusion syndrome associated with transient hydrops fetalis observed in the donor after therapeutic amnioreduction at 22 weeks of gestation. After the amnioreduction, the bladder of the donor could be visualized and the donor subsequently began to make amniotic fluid, with spontaneous regression of hydrops fetalis. It is suspected that after therapeutic amnioreduction, intrauterine hemodynamic changes occurred and the donor developed transient hydrops fetalis due to volume overload.

Adult↗

PubMed2001

Clearance of group X secretory phospholipase A(2) via mouse phospholipase A(2) receptor.

Given the potent hydrolyzing activity toward phosphatidylcholine, group X secretory phospholipase A(2) (sPLA(2)-X) elicits a marked release of arachidonic acid linked to the potent production of lipid mediators in various cell types. We have recently shown that sPLA(2)-X can also act as a ligand for mouse phospholipase A(2) receptor (PLA(2)R). Here, we found that sPLA(2)-X was internalized and degraded via binding to PLA(2)R associated with the diminished prostaglandin E(2) (PGE(2)) formation in PLA(2)R-expressing Chinese hamster ovary (CHO) cells compared to CHO cells. Indirect immunocytochemical analysis revealed that internalized sPLA(2)-X was co-localized with PLA(2)R in the punctate structures in PLA(2)R-expressing CHO cells. Moreover, in mouse osteoblastic MC3T3-E(1) cells that endogenously express the PLA(2)R, the internalized sPLA(2)-X was localized in lysosomes. These findings demonstrate that PLA(2)R acts as a clearance receptor for sPLA(2)-X to suppress its strong enzymatic activity.

3T3 Cells↗

PubMed2000

Identification of group X secretory phospholipase A(2) as a natural ligand for mouse phospholipase A(2) receptor.

Phospholipase A(2) receptor (PLA(2)R) mediates various biological responses elicited by group IB secretory phospholipase A(2) (sPLA(2)-IB). The recently cloned group X sPLA(2) (sPLA(2)-X) possesses several structural features characteristic of sPLA(2)-IB. Here, we detected a specific binding site of sPLA(2)-X in mouse osteoblastic MC3T3-E(1) cells. Cross-linking experiments demonstrated its molecular weight (180 kDa) to be similar to that of PLA(2)R. In fact, sPLA(2)-X was found to bind the recombinant PLA(2)R expressed in COS-7 cells, and its specific binding detected in mouse lung membranes was abolished by the deficiency of PLA(2)R. These findings demonstrate sPLA(2)-X to be one of the high-affinity ligands for mouse PLA(2)R.

Animals↗

PubMed2000

Enhanced tissue expression and elevated circulating level of phospholipase A(2) receptor during murine endotoxic shock.

Phospholipase A(2) receptor (PLA(2)R) mediates a variety of biological responses elicited by mammalian secretory phospholipase A(2) (sPLA(2)). In mice, group IB sPLA(2) (sPLA(2)-IB) acts as an endogenous ligand of PLA(2)R, and analysis of PLA(2)R-deficient mice has demonstrated a critical role of the sPLA(2)-IB/PLA(2)R system in the production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) in the development of endotoxic shock. Here, we generated specific antibodies against a recombinant soluble form of PLA(2)R and examined its expression in the lung and spleen where a remarkable elevation of TNF-alpha expression has been observed during endotoxemia. Immunohistochemical analysis revealed the expression of PLA(2)R in type II alveolar epithelial cells and a subset of splenic lymphocytes, and its expression levels were markedly enhanced at 1 h after endotoxin challenge. Analysis with a newly developed sandwich enzyme-linked immunosorbent assay system revealed the presence of a soluble form of PLA(2)R in plasma of wild-type mice compared with its absence in plasma of PLA(2)R-deficient mice. After exposure to endotoxin, its circulating level was significantly elevated to the maximum level at 2-3 h after the treatment. These results suggest that tissue expression and the circulating level of PLA(2)R are elevated during murine endotoxemia, which might be relevant to its potential roles in the production of proinflammatory mediators during the development of inflammatory conditions.

3T3 Cells↗

PubMed2000

Structures, enzymatic properties, and expression of novel human and mouse secretory phospholipase A(2)s.

Mammalian secretory phospholipase A(2)s (sPLA(2)s) form a family of structurally related enzymes that are involved in a variety of physiological and pathological processes via the release of arachidonic acid from membrane phospholipids or the binding to specific membrane receptors. Here, we report the cloning and characterization of a novel sPLA(2) that is the sixth isoform of the sPLA(2) family found in humans. The novel human mature sPLA(2) consists of 123 amino acids (M(r) = 14,000) and is most similar to group IIA sPLA(2) (sPLA(2)-IIA) with respect to the number and positions of cysteine residues as well as overall identity (51%). Therefore, this novel sPLA(2) should be categorized into group II and called group IIE (sPLA(2)-IIE) following the recently identified group IID sPLA(2) (sPLA(2)-IID). The enzymatic properties of recombinant human sPLA(2)-IIE were almost identical to those of sPLA(2)-IIA and IID in terms of Ca(2+) requirement, optimal pH, substrate specificity, as well as high susceptibility to the sPLA(2) inhibitor indoxam. Along with the biochemical properties of proteins, genetic and evolutional similarities were also observed among these three types of group II sPLA(2)s as to the chromosomal location of the human gene (1p36) and the exon/intron organization. The expression of sPLA(2)-IIE transcripts in humans was restricted to the brain, heart, lung, and placenta in contrast to broad expression profiles for sPLA(2)-IIA and -IID. In sPLA(2)-IIA-deficient mice, the expression of sPLA(2)-IIE was markedly enhanced in the lung and small intestine upon endotoxin challenge, which contrasted with the reduced expression of sPLA(2)-IID mRNA. In situ hybridization analysis revealed elevation of sPLA(2)-IIE mRNA at alveolar macrophage-like cells in the lung of endotoxin-treated mice. These findings suggest a distinct functional role of novel sPLA(2)-IIE in the progression of inflammatory processes.

Amino Acid Sequence↗

PubMed2000

Inhibition of hyaluronan synthesis by vesnarinone in cultured human myofibroblasts.

Hyaluronan (HA), which is a major component of the extracellular matrix (ECM), is regulated during myofibroproliferative responses to numerous forms of inflammatory stimuli. It is a key factor involved in cellular migration and adherence. The development of a potent and non-toxic inhibitor of HA synthesis would open up a new avenue for the treatment of fibrocontractive diseases such as pulmonary fibrosis and liver cirrhosis. In this study, the effects of vesnarinone (OPC-8212: 3,4-dihydro-6-[4-(3, 4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone) on the secretion of HA in human myofibroblast cell lines (MRC-5 and LI90 cells, referred to as pulmonary and hepatic myofibroblasts, respectively) were examined. Vesnarinone specifically and dose-dependently inhibited HA secretion by myofibroblasts up-regulated by fetal calf serum (FCS). The treatment of vesnarinone did not modify the phenotype of myofibroblast cells in culture. Vesnarinone also potently inhibited the HA secretion by the two myofibroblast cell lines up-regulated by transforming growth factor-beta1 (TGF-beta1) or tumor necrosis factor-alpha (TNF-alpha). The addition of vesnarinone to myofibroblasts resulted in a significant decrease of HA synthase (HAS) activity, with or without the addition of FCS or either cytokine. These findings suggest that vesnarinone inhibits the secretion of HA in myofibroblasts by specifically suppressing HAS activity, and may therefore prove useful for the treatment of chronic inflammation and tissue fibrosis.

Cell Line↗

PubMed2000

Effect of branched-chain amino acids on the plasma concentration of uridine does not occur via the action of glucagon or insulin.

To examine whether branched-chain amino acids affect the plasma concentration of uridine, we administered branched-chain amino acids (L-isoleucine, 2.85 g, L-leucine 5.71 g, and L-valine, 3.43 g) orally to 6 healthy subjects. Plasma uridine and glucose decreased by 44% and 12%, respectively, together with an increase in plasma isoleucine, leucine, and valine 90 minutes after administration. However, branched-chain amino acids did not affect the plasma concentration and urinary excretion of purine bases (hypoxanthine, xanthine, and uric acid) and uridine or the plasma concentration of insulin, glucagon, and cyclic adenosine monophosphate (cAMP). Since small amounts of regular insulin, which were found to decrease plasma glucose more than the amino acids, did not decrease the plasma concentration of uridine, these results suggest that plasma uridine was decreased by a direct effect of the branched-chain amino acids on the cellular uptake and/or release of uridine.

Adult↗

PubMed2000

Investigation of TTV by in situ hybridization in patients with chronic hepatitis.

To clarify whether TT virus (TTV) was present in liver tissues, 12 liver tissue samples from patients with chronic hepatitis positive for TTV in their serum and 11 samples from serum-negative patients were obtained by needle biopsies and investigated using in situ hybridization. Positive staining was observed in nine (75%) of 12 cases positive for TTV (serum-positive group) and three (27.3%) of 11 cases negative for TTV (serum-negative group) (P=0.061). Three kinds of staining patterns were observed: nuclear, cytoplasmic and both. In 58.3% (7/12) of the patients positive for TTV staining, the stained areas were found in both the nucleus and cytoplasm. Only cytoplasmic staining was observed in three cases from the serum-positive group. Only nuclear staining was observed in two cases from the serum-negative group. No significant differences were found in the clinical background between the in situ hybridization-positive and -negative groups, and between the serum-positive and -negative groups. The present study shows that TTV exists in the liver tissue, especially in hepatocytes, of chronic hepatitis patients and that the localization of TTV in the cell is different from case to case, although why this is so remains to be clarified.

Journal Article↗

PubMed2000

Comparative study on the correlation of plasma gamma-aminobutyric acid and pipecolic acid with liver function in patients with liver cirrhosis.

gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, elevated in plasma of patients with liver cirrhosis. Pipecolic acid (PA), a metabolite of lysine, and known to be a GABA receptor agonist, is also seen high levels in the plasma. To clarify the relationship of GABA, PA and liver function, plasma GABA and PA in three groups of chronic liver diseases (compensated cirrhosis, decompensated cirrhosis and decompensated cirrhosis with hepatic encephalopathy, HE) were analyzed and their liver functions were compared. This analysis demonstrated that both plasma GABA and PA were higher in these patients than in normal subjects. Plasma PA, but not plasma GABA, was closely correlated with plasma ammonia concentration in each group. No correlation was noted between plasma GABA and PA in each group. Plasma pipecolic acid was significantly higher in patients with esophageal varices than in patients with no varices. These findings suggest that increased PA may reflect the degree of portal hypertension. Although both GABA and PA are increased in chronic liver disease, they may have a different origin and disappearance rate including metabolic mechanism.

Journal Article↗

PubMed2000

Effect of TEI-6720, a xanthine oxidase inhibitor, on the nucleoside transport in the lung cancer cell line A549.

To examine the effect of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid (TEI-6720), an inhibitor of xanthine oxidase, on purine metabolism in the lung cancer cell line A549, the activities of adenosine deaminase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, hypoxanthine guanine phosphoribosyltransferase, xanthine oxidase, and guanase together with pyrimidine nucleoside phosphorylase were measured with or without the addition of TEI-6720, and the extracellular concentrations of hypoxanthine, xanthine, inosine, uracil, and uridine were measured after the addition of inosine or uridine to the incubation medium with or without TEI-6720. Moreover, the Na-independent nucleoside transport was determined in A549 cells with or without TEI-6720. TEI-6720 inhibited the activity of xanthine oxidase in A549 cells, but did not affect other enzymes. During incubation, TEI-6720 not only prevented a decrease in the inosine concentration in inosine-containing medium, but also a decrease in the uridine concentration in uridine-containing medium. Furthermore, the Na-independent transport of uridine was inhibited by TEI-6720 with a K(i) value of 4.1 micromol/l. These results indicate that TEI-6720 is an inhibitor of the Na-independent nucleoside transport of uridine and inosine, as well as xanthine oxidase.

Allopurinol↗

PubMed2000

The inhibitory effect of cisplatin in combination with irradiation on lung tumor cell growth is due to induction of tumor cell apoptosis.

Chemoradiation is becoming an important method of treatment of advanced lung cancer. Although many studies have demonstrated the efficacy of chemoradiation against lung tumors, the mechanism of its effect is still poorly understood. In this study, we analyzed the combined effect of cisplatin (CDDP) and irradiation on human lung cancer cell lines (PC-9 and Lu 134A) in vitro using MTT assay and isobologram analysis. To study whether the combined effect is due to induction of tumor cell apoptosis, we further quantified the nuclear fragmentation of tumor cells by flow cytometric analysis. Our study revealed that a combination of cisplatin and irradiation had an additive inhibitory effect on both PC-9 (adenocarcinoma) and Lu 134A (small cell carcinoma) tumor cell growth. Cisplatin improved the sensitivity of tumor cells to irradiation. The use of both cisplatin and irradiation doses could be reduced without decreasing the inhibitory effect. The additive inhibitory effect was correlated positively with the levels of tumor cell nuclear fragmentation. We concluded that combination treatment with cisplatin and irradiation is effective against lung tumors, not only small cell carcinoma but also non-small cell carcinoma, and the inhibitory effect was due to induction of tumor cell apoptosis.

Adenocarcinoma↗

PubMed1999

Kupffer cells from Schistosoma mansoni-infected mice participate in the prompt type 2 differentiation of hepatic T cells in response to worm antigens.

Infection with Schistosoma mansoni, a portal vein-residing helminth, is well known to generate life cycle-dependent, systemic immune responses in the host, type 1 deviation during the prepatent period, and type 2 polarization after oviposition. Here we investigated local immunological changes in the liver after infection. Unlike splenocytes, hepatic lymphocytes from infected mice during the prepatent period already produced a higher amount of IL-4 and a lesser amount of IFN-gamma than those from uninfected mice. Hepatic lymphocytes, particularly conventional T cells, but not NK1.1+ T cells, promptly produced IL-4 in response to worm products, soluble worm Ag preparation (SWAP), whenever presented by Kupffer cells from infected mice. The hepatic lymphocytes that had been stimulated with SWAP presented by infected mice-derived Kupffer cells produced a huge amount of IL-4, IL-13, and IL-5 as well as little IFN-gamma in response to immobilized anti-CD3 mAb. Kupffer cells from uninfected mice produced IL-6 and IL-10, but not IL-12 or IL-18, in response to SWAP stimulation and gained the potential to additionally produce IL-4 and IL-13 after the infection. These results suggested that prompt type 2 deviation in the liver after the infection might be due to the alteration of Kupffer cells that induces SWAP-mediated type 2-development of hepatic T cells.

Animals↗

PubMed1999

Purified group X secretory phospholipase A(2) induced prominent release of arachidonic acid from human myeloid leukemia cells.

Group X secretory phospholipase A(2) (sPLA(2)-X) possesses several structural features characteristic of both group IB and IIA sPLA(2)s (sPLA(2)-IB and -IIA) and is postulated to be involved in inflammatory responses owing to its restricted expression in the spleen and thymus. Here, we report the purification of human recombinant COOH-terminal His-tagged sPLA(2)-X, the preparation of its antibody, and the purification of native sPLA(2)-X. The affinity-purified sPLA(2)-X protein migrated as various molecular species of 13-18 kDa on SDS-polyacrylamide gels, and N-glycosidase F treatment caused shifts to the 13- and 14-kDa bands. NH(2)-terminal amino acid sequencing analysis revealed that the 13-kDa form is a putative mature sPLA(2)-X and the 14-kDa protein possesses a propeptide of 11 amino acid residues attached at the NH(2) termini of the mature protein. Separation with reverse-phase high performance liquid chromatography revealed that N-linked carbohydrates are not required for the enzymatic activity and pro-sPLA(2)-X has a relatively weak potency compared with the mature protein. The mature sPLA(2)-X induced the release of arachidonic acid from phosphatidylcholine more efficiently than other human sPLA(2) groups (IB, IIA, IID, and V) and elicited a prompt and marked release of arachidonic acid from human monocytic THP-1 cells compared with sPLA(2)-IB and -IIA with concomitant production of prostaglandin E(2). A prominent release of arachidonic acid was also observed in sPLA(2)-X-treated human U937 and HL60 cells. Immunohistochemical analysis of human lung preparations revealed its expression in alveolar epithelial cells. These results indicate that human sPLA(2)-X is a unique N-glycosylated sPLA(2) that releases arachidonic acid from human myeloid leukemia cells more efficiently than sPLA(2)-IB and -IIA.

Animals↗