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Biomedical subjects

A Harada

Publications and source records attributed to A Harada.

At least 73 records · Page 4Linked to original sources
PubMed1999

A successful surgical repair of the hepatic hydrothorax using pneumoperitoneum: report of a case.

A successful surgical repair of a right hepatic hydrothorax in the absence of ascites is reported. A technetium-99m scintigram that was injected intraperitoneally provided evidence of a one-way flow of fluid from the peritoneal to pleural cavity. To identify any possible minute defects in the diaphragm, carbon dioxide was insufflated into the peritoneal cavity during the operation. We performed a direct suture of the defect observed on the diaphragm. The pleural effusion subsequently vanished after the operation.

Humans↗
PubMed1999

Aortic stump tailoring with GRF glue and a felt strip.

We describe herein a new technique of aortic stump tailoring for aortic dissection. This method involves the application of gelatine-resorcin-formalin (GRF) glue and a felt strip, with manipulation using the balloon of an endotracheal tube. The conjoined wall consists of three layers, but it is completed like a single layer. This procedure facilitates anastomosis to the graft in the next step.

Aortic Dissection↗
PubMed1999

Rotational acetabular osteotomy for advanced osteoarthrosis secondary to dysplasia of the hip. Results at 6-11 years postoperatively.

Clinical and radiological studies were done on the results of rotational acetabular osteotomy for advanced osteoarthrosis secondary to dysplasia of 29 adult hips followed up for 6 to 11 years postoperatively (mean 8 years). Clinical evaluation by Merle d'Aubigne and Postel's system showed improvement from a preoperative mean of 12.8 to a follow-up mean of 14.8, with aggravation being observed in 8 joints. Radiologically, this procedure produced adequated improvement regarding femoral head coverage, but improvement in joint congruency could not necessarily be obtained due to joint deformity and progression of arthrosis, with aggravation of joint congruency being observed in 6 joints. The most important factor influencing the postoperative results of this procedure was postoperative joint congruency. If the postoperative joint congruency is satisfactory, with the joint congruent index being more than 6.0, progression of arthrosis can be prevented in the long term by this procedure, even in advanced cases.

Acetabulum↗
PubMed1999

p42/p44 mitogen-activated protein kinase activation is involved in prostaglandin F2alpha-induced interleukin-6 synthesis in osteoblasts.

Prostaglandin F2alpha (PGF2alpha) significantly induced p42/p44 mitogen-activated protein (MAP) kinase activity in osteoblast-like MC3T3-E1 cells. PD98059, a selective inhibitor of MAP kinase kinase, inhibited PGF2alpha-induced interleukin-6 (IL-6) synthesis as well as PGF2alpha-induced p42/p44 MAP kinase activation. PD98059 suppressed the IL-6 synthesis induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC) activator, or NaF, an activator of heterotrimeric GTP-binding protein, as well as the p42/p44 MAP kinase activation by TPA or NaF. Calphostin C, a highly potent and specific inhibitor of PKC, inhibited the PGF2alpha-induced p42/p44 MAP kinase activity. These results strongly suggest that PKC-dependent p42/p44 MAP kinase activatioin is involved in PGF2alpha-induced IL-6 synthesis in osteoblasts.

Animals↗
PubMed1999

Interleukin-8 inhalation directly provokes bronchoconstriction in guinea pigs.

BACKGROUND: Although it has been reported that the concentration of interleukin (IL)-8 in nasal lavage fluid and sputum and its production in bronchial epithelium were increased in asthmatic subjects, the direct effects of IL-8 on the airways in vivo is unclear. METHODS: We examined bronchoconstriction in response to IL-8 inhalation through an endotracheal cannula in anesthetized, artificially ventilated guinea pigs. RESULTS: Inhalation of IL-8 at concentrations of 1 and 10 microg/ml caused significant bronchoconstriction, as revealed by the elevation of pressure at the airway opening. Moreover, the bronchoconstriction induced by IL-8 was significantly inhibited by the antihistamines diphenhydramine and terfenadine, suggesting the involvement of histamine release in the IL-8-induced bronchoconstriction. No significant leukocyte infiltration was observed in the bronchoalveolar lavage fluid or histologic findings 25 min after the first IL-8 inhalation. CONCLUSIONS: IL-8 provokes bronchoconstriction without leukocyte accumulation in the airways, mediated in part by histamine release, in guinea pigs.

Administration, Inhalation↗
PubMed1999

Prostaglandin D2 induces interleukin-6 synthesis via Ca2+ mobilization in osteoblasts: regulation by protein kinase C.

We previously showed that prostaglandin (PG) D2 stimulates Ca2+ influx from extracellular space and activates phosphoinositidic (PI)-hydrolyzing phospholipase C and phosphatidylcholine (PC)-hydrolyzing phospholipase D independently from PGE2 or PGF2alpha in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of PGD2 on the synthesis of interleukin-6 (IL-6) and its regulatory mechanism in MC3T3-E1 cells. PGD2 significantly stimulated IL-6 synthesis dose-dependently in the range between 10 nM and 10 microM. The depletion of extracellular Ca2+ by EGTA reduced the PGD2-induced IL-6 synthesis. TMB-8, an inhibitor of intracellular Ca2+ mobilization, significantly inhibited the PGD2-induced IL-6 synthesis. On the other hand, calphostin C, a specific inhibitor of protein kinase C (PKC), enhanced the synthesis of IL-6 induced by PGD2. In addition, U-73122, an inhibitor of phospholipase C, and propranolol, a phosphatidic acid phosphohydrolase inhibitor, enhanced the PGD2-induced IL-6 synthesis. These results strongly suggest that PGD2 stimulates IL-6 synthesis through intracellular Ca2+ mobilization in osteoblasts, and that the PKC activation by PGD2 itself regulates the over-synthesis of IL-6.

Animals↗
PubMed1999

A monoclonal antibody, 3A10, recognizes a specific amino acid sequence present on a series of developmentally expressed brain proteins.

Immunoblotting showed that a monoclonal antibody, 3A10, binds to a series of rat brain-specific antigens with molecular masses of 150-, 120-, 118-, 106-, 104-, 79-, and 77-kDa. The expression of 3A10 antigens is dependent on the developmental stage of the brain; only the 106-kDa antigen is detected during embryonic stages of rat brain development, while the expression of the remaining 6 antigens starts after birth and reaches a maximum during postnatal days 15-21. Detection of the 3A10 antigens in cultured neuronal and glial cells derived from cerebral cortices of rat brain at embryonic day 18 showed that the 77-, 79-, 106-, and 150-kDa antigens are specifically expressed in neuronal cells. The 77-kDa antigen was purified and identified as synapsin I by amino acid sequence analyses of the peptide fragments isolated after Achromobacter protease I treatment. During the isolation of 3A10-reactive proteins by immunological screening of cDNA libraries constructed from adult rat brain, we found that all of the 3A10-reactive clones contain nucleotide sequences encoding the unique amino acid sequence TRSP(S, R,G)P. Analyses of 3A10-binding to various synthetic peptides showed that the monoclonal antibody recognizes a specific conformational structure formed by either the TRSPXP sequence or similar amino acid sequences that are expressed on a series of developmentally expressed brain proteins.

Amino Acid Sequence↗
PubMed1999

Interleukin-8 controls bacterial transepithelial translocation at the cost of epithelial destruction in experimental shigellosis.

In shigellosis, the network of cellular interactions mediated by a balance of pro- and anti-inflammatory cytokines or chemokines is clearly tipped toward acute destructive inflammation of intestinal tissues by the bacterial invader. This work has addressed the role played by interleukin-8 (IL-8) in a rabbit model of intestinal invasion by Shigella flexneri. IL-8, which is largely produced by the epithelial cells themselves, appears to be a major mediator of the recruitment of polymorphonuclear leukocytes (PMNs) to the subepithelial area and transmigration of these cells through the epithelial lining. Neutralization of IL-8 function by monoclonal antibody WS-4 caused a decrease in the amount of PMNs streaming through the lamina propria and the epithelium, thus significantly attenuating the severity of epithelial lesions in areas of bacterial invasion. These findings are in agreement with our previous work (31). In contrast to the PMNs, the bacteria displayed increased transepithelial translocation, as well as overgrowth in the lamina propria and increased passage into the mesenteric blood. By mediating eradication of bacteria at their epithelial entry site, although at the cost of severe epithelial destruction, IL-8 therefore appears to be a key chemokine in the control of bacterial translocation.

Animals↗
PubMed1999

Active participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease.

We examined the molecular pathogenesis of graft-versus-host disease-associated (GVHD-associated) liver injury in mice, focusing on the role of chemokines. At the second week after cell transfer in the parent-into-F1 model of GVHD, CD8(+) T cells -- especially donor-derived CD8(+) T cells -- infiltrated the liver, causing both portal hepatitis and nonsuppurative destructive cholangitis (NSDC). These migrating cells expressed CCR5. Moreover, macrophage inflammatory protein-1alpha (MIP-1alpha), one of the ligands for CCR5, was selectively expressed on intralobular bile duct epithelial cells, endothelial cells, and infiltrating macrophages and lymphocytes. Administration of anti-CCR5 antibody dramatically reduced the infiltration of CCR5(+)CD8(+) T lymphocytes into the liver, and consequently protected against liver damage in GVHD. The levels of Fas ligand (FasL) mRNA expression in the liver were also decreased by anti-CCR5 antibody treatment. Anti-MIP-1alpha antibody treatment also reduced liver injury. These results suggest that MIP-1alpha-induced migration of CCR5-expressing CD8(+) T cells into the portal areas of the liver plays a significant role in causing liver injury in GVHD; thus, CCR5 and its ligand may be the novel target molecules of therapeutic intervention of hepatic GVHD.

Acute Disease↗
PubMed1999

Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis.

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble member of the tumor necrosis factor receptor family of proteins and plays an important role in the negative regulation of osteoclastic bone resorption. Whether OPG/OCIF circulates in human blood and how its level changes under pathological conditions is not known. To address these issues, a panel of monoclonal antibodies was generated against recombinant OPG/OCIF and screened for reactivity with solid-phase monomeric and homodimeric forms of the recombinant protein. Antibodies that showed high affinity for both forms of OPG/OCIF and those that selectively recognized the homodimer were identified, enabling development of two types of sensitive enzyme-linked immunosorbent assay (ELISA): one that detects both forms of OPG/OCIF equally and one specific for the homodimer. Characterization of circulating OPG/OCIF with these ELISAs revealed that the protein exists in human serum mainly in the monomeric form. The serum concentration of OPG/OCIF increased with age in both healthy Japanese men and women, and was significantly higher in postmenopausal women with osteoporosis than in age-matched controls. Within the osteoporotic group, serum OPG/OCIF concentrations were higher in patients with low bone mass. Serum OPG/OCIF concentrations were also significantly increased in those postmenopausal women with a high rate of bone turnover, as determined by increased serum bone-specific alkaline phosphatase and urinary excretion of pyridinoline and deoxypyridinoline. The results suggested that circulating OPG/OCIF levels are regulated by an age-related factor(s) and that the increased serum concentration may reflect a compensative response to enhanced osteoclastic bone resorption and the resultant bone loss rather than a cause of osteoporosis.

Adult↗
PubMed1999

[An elderly case of juvenile muscular atrophy in the unilateral upper extremity with tremor in both hands].

A 75-year-old man had noticed muscle atrophy and weakness of his right hand and forearm at the age of 25. The symptoms slowly progressed and then stopped. Right hand tremor appeared at about age 40. There was no symptom in his left upper extremity, and his gait was normal. He now shows severe muscle atrophy in his right hand and forearm. There was distally dominant weakness of the right upper extremity and his hand grip was 0 kg on the right and 25 kg on the left. On admission there was no weakness in the bilateral lower extremities. He had postural tremor in both hands and fingers. The tendon reflexes were hypoactive in the upper extremities and normal in the lower extremities. Abnormalities in the superficial sensation were unremarkable, whereas vibration sensation in both the upper and lower extremities was mildly disturbed. Electromyography revealed chronic denervation, especially in the right upper extremity. The sensory nerve conduction study results and somatosensory evoked potentials in the upper extremities were normal. Cervical MRI demonstrated spondylotic changes, canal stenosis from the C5 to C7 levels, and compression of the spinal cord. His hand tremor was dominant on the right with a peak frequency of about 7 Hz. Tremor frequency and power were decreased by mechanical load. Hirayama's disease (juvenile muscular atrophy of unilateral upper extremity) was the most probable diagnosis, although aging might have produced various additional abnormalities. The tremor seen in this patient showed characteristics of enhanced physiological tremor.

Aged↗
PubMed1999

[An elderly case of chronic inflammatory demyelinating polyneuropathy with acute onset in the course of diabetes mellitus].

A 77-year-old man was admitted because of muscle weakness in both upper and lower extremities. Diabetes mellitus was diagnosed in 1988 and he had been treated by oral hypoglycemic agents. He had a common cold at the end of January, 1997. Muscle weakness appeared in the upper extremities, followed by the lower extremities at the end of February. No sensory disturbance or dysuria was recognized. Nerve conduction study revealed distally dominant demyelinating polyneuropathy. Guillain-Barré's syndrome was diagnosed and he recovered completely following immunological absorption therapy (IAT). However, he had quadriplegia again at the end of April. He was treated by IAT combined with corticosteroid and has shown no relapse. In June, 1997, gastric cancer was detected by upper gastrointestinal fiberscopy and subtotal gastrectomy was performed. Judging from this clinical course, this case seems to be chronic inflammatory demyelinating polyneuropathy (CIDP) with acute onset. Many kinds of causes often contribute to the pathogenesis of neuropathy in the elderly. So in cases of progression or worsening, we should consider such possibilities and it is necessary not to exclude treatable causes of neuropathy.

Aged↗
PubMed1999

The serum interleukin 8 level reflects hepatic mitochondrial redox state in hyperthermochemohypoxic isolated liver perfusion with use of a venovenous bypass.

BACKGROUND: We have recently developed a simple method of hyperthermochemohypoxic isolated liver perfusion (HILP) as a regional therapy for unrecognized liver micrometastases. However, little is known about the influence of HILP on cytokine production and liver function. We investigated the influence of HILP on interleukin 8 (IL-8) production and the hepatic mitochondrial function and assessed the relationship between these 2 parameters. We also measured the serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels to examine the involvement of HILP-induced cytokines in the tumor response. METHODS: Sixteen patients with metastatic liver tumors were randomly assigned to undergo hepatectomy with HILP (group A, n = 9) or hepatectomy alone (group B, n = 7). The isolated liver was perfused for 30 minutes with Ringer's lactate solution containing chemotherapeutic agents warmed to 42 degrees C to 43 degrees C without oxygenation. RESULTS: The serum IL-8 levels in group A were markedly increased, with peaks at 3 hours after reperfusion, which was significantly higher than levels in group B (P < .01). In group A the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, decreased during perfusion and was gradually restored to the preperfusion level 1 hour after reperfusion. However, in group B it decreased during hepatectomy but rapidly recovered 5 minutes after hepatectomy. There was a significant negative correlation between the peak serum IL-8 level and the initial velocity of arterial ketone body ratio recovery for the first 5 minutes after reperfusion r = -0.83, P < .001). The serum TNF-alpha and IL-1 beta were temporarily detected only in 3 of 9 patients in group A. CONCLUSIONS: We have shown that HILP resulted in augmented IL-8 release but not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects the hepatic mitochondrial redox state. These findings suggest that IL-8 production may be associated with hepatic mitochondrial impairment during ischemia. This work may contribute to new therapeutic strategies not only for hepatic ischemia reperfusion injury but also for metastatic liver tumors.

Aged↗
PubMed1999

Control of photoinduced electron transfer from zinc-porphyrin to methyl viologen by supramolecular formation between monoclonal antibody and zinc-porphyrin.

Photoinduced electron transfer from tetrakis(4-carboxy-phenyl porphyrin)-zinc complex (Zn-TCPP) to an acceptor molecule (methyl viologen; MV2+) has been found to be controlled by the complex formation of monoclonal antibody 03-1 for the porphyrin (TCPP) and Zn-TCPP. Although there are no ground-state interactions between Zn-TCPP and MV2+ for a 2:1 complex of antibody 03-1 and Zn-TCPP, the fluorescence of Zn-TCPP is quenched by the addition of MV2+. The Stern-Volmer plots and emission lifetime studies show that there is a long-range electron transfer through the antibody 03-1.

Antibodies, Monoclonal↗
PubMed1999

Attenuated liver fibrosis and depressed serum albumin levels in carbon tetrachloride-treated IL-6-deficient mice.

Chronic intermittent injection of carbon tetrachloride (CCl4) for more than 10 weeks induced liver fibrosis in mice, as evidenced by positive Azan staining and increased intrahepatic collagen content. Preceding the onset of liver fibrosis, interleukin-6 (IL-6) gene expression was enhanced in liver and immunoreactive IL-6 was detected in infiltrating inflammatory cells. To delineate the role of IL-6 in this process, we treated IL-6-deficient mice with CCl4 in a similar manner for 12 weeks, after which fibrotic changes were less evident and serum albumin levels were lower in IL-6-deficient than wild-type mice. Moreover, CCl4-induced expression of transforming growth factor beta1 and hepatocyte growth factor genes in liver was significantly reduced in IL-6-deficient mice. Thus, IL-6 may be vitally involved in fibrotic changes and maintenance of serum albumin levels, partly by modulating intrahepatic expression of these cytokines.

Animals↗
PubMed1998

Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.

Microtubule-dependent motor, murine KIF3B, was disrupted by gene targeting. The null mutants did not survive beyond midgestation, exhibiting growth retardation, pericardial sac ballooning, and neural tube disorganization. Prominently, the left-right asymmetry was randomized in the heart loop and the direction of embryonic turning. lefty-2 expression was either bilateral or absent. Furthermore, the node lacked monocilia while the basal bodies were present. Immunocytochemistry revealed KIF3B localization in wild-type nodal cilia. Video microscopy showed that these cilia were motile and generated a leftward flow. These data suggest that KIF3B is essential for the left-right determination through intraciliary transportation of materials for ciliogenesis of motile primary cilia that could produce a gradient of putative morphogen along the left-right axis in the node.

Animals↗
PubMed1998

Pivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice.

Thymus and activation-regulated chemokine (TARC) is a recently identified lymphocyte-directed CC chemokine which specifically chemoattracts T helper type 2 CD4(+) T cells in human. To establish the pathophysiological roles of TARC in vivo, we investigated whether a monoclonal antibody (mAb) against TARC could inhibit the induction of hepatic lesions in murine model using Propionibacterium acnes and lipopolysaccharide (LPS). P. acnes-induced intrahepatic granuloma formation in the priming phase is essential to the subsequent liver injury elicited by a low dose of LPS. The priming phase appears to be dominated by Th1 type immune responses determined by the profile of chemokine and chemokine receptor expression. TARC was selectively produced by granuloma-forming cells, and CC chemokine receptor 4 (CCR4)-expressing CD4(+) T cells migrated into the liver after LPS administration. In vivo injection of anti-TARC mAb just before LPS administration protected the mice from acute lethal liver damage, which was accompanied by a significant reduction of both CCR4 mRNA expression and IL-4 production by liver-infiltrating CD4(+) T cells. Moreover, both TNF-alpha and Fas ligand expressions in the liver were decreased by anti-TARC treatment. These results suggest that recruitment of IL-4-producing CCR4(+) CD4(+) T cells by granuloma-derived TARC into the liver parenchyma may be a key cause of massive liver injury after systemic LPS administration.

Animals↗