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Biomedical subjects

K Hirai

Publications and source records attributed to K Hirai.

At least 145 records · Page 8Linked to original sources

Acute eosinophilic pneumonia associated with smoke from fireworks.

We report a case of acute eosinophilic pneumonia (AEP). Although the patient had been a habitual cigarette smoker for over 4 months, he had had not any respiratory distress. After he inhaled smoke from fireworks for 3 consecutive nights, the patient began to complain of cough, fever and dyspnea. He showed leukocytosis of 16,200/microl and hypoxemia of 58.1 torr. Chest radiograph showed bilateral infiltrates with Kerley A and B lines. The bronchoalveolar lavage fluid revealed 38.5% eosinophils. He was diagnosed as AEP. In this patient, inhaling of smoke from fireworks was clinically suspected to be associated with the induction of AEP.

Acute Disease↗

Eotaxin levels in pleural effusions: comparison with monocyte chemoattractant protein-1 and IL-8.

OBJECTIVE: In order to investigate the role of eotaxin in pleural diseases, we measured eotaxin in pleural effusions and studied the relationship between eotaxin levels and recruitment of inflammatory cells, particularly eosinophils. Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) levels were also measured for comparison. METHODS: We evaluated 47 pleural effusion samples, 7 transudates and 40 exudates. The exudates consisted of 19 malignant, 11 tuberculous, and 5 parapneumonic effusions, and 5 effusions of other etiologies. Chemokine levels were measured by specific sandwich enzyme-linked immunosorbent assays. RESULTS: Eotaxin was detected in all samples examined, but the levels did not differ significantly among the exudates. There was no significant correlation between the levels of eotaxin and MCP-1 or IL-8. The level of eotaxin but not the others was significantly higher in eosinophilic effusions (>10% eosinophils among white blood cells in the fluid) than in non-eosinophilic fluids. The number of eosinophils in pleural effusions was significantly correlated with the eotaxin levels, but not with the levels of other chemokines. The number of neutrophils was significantly correlated with IL-8 but not with the others. CONCLUSIONS: Results suggest that eotaxin contributes to the migration of eosinophils in pleural inflammation. Taken together with the correlation between IL-8 and neutrophils, it appears that the predominant type of pleural inflammatory infiltrate is controlled, at least in part, by the subgroup of chemokines expressed in the pleural space.

Chemokine CCL11↗

Correlation between erythropoietin and lactate in humans during altitude exposure.

The plasma concentrations of both immunoreactive erythropoietin (EPO) and lactate were determined in four healthy untrained subjects at sea level and on the 2nd or 3rd day at altitudes (1,300 and 3,500 m). The mean plasma EPO (18.8 +/- 1.6 mU/ml at sea level) increased significantly on the 3rd day at 1,300 m (25.5 +/- 2.0 mU/ml, p < 0. 05) and showed an almost three-fold increase on the 2nd day at 3,500 m (53.5 +/- 3.7 mU/ml, p < 0.001). Likewise, the mean plasma lactate at 3,500 m (3.98 +/- 0.27 mmol/l) was 3.6 times as high as that at sea level (1.11 +/- 0.05 mmol/l) (p < 0.001). The plasma EPO concentrations were found to correlate well with the lactate concentrations at sea level and altitudes (r = 0.86, p < 0.01). These results are consistent with the well-known EPO/lactate response to altitudes and suggest that the circulating EPO concentration as well as blood lactate concentration can be used as an index of anaerobic condition.

Adult↗

Differences in TNF-alpha producing activity from murine peritoneal macrophages induced by lipopolysaccharides of Prevotella heparinolytica and Porphyromonas gingivalis.

We compared the effects of LPSs from P. gingivalis and P. heparinolytica on the induction of tumor necrosis factor-alpha (TNF-alpha) production by murine peritoneal macrophages. The lipopolysaccharide (LPS) preparation from P. gingivalis showed a typical ladder pattern in SDS-PAGE, whereas that from P. heparinolytica formed several stained bands without a ladder pattern. When the macrophages from C3H/HeJ mice were incubated with P. gingivalis LPS, the level of TNF-alpha released in the culture supernatants was significantly higher than that with P. heparinolytica. All tested reagents except genistein strongly inhibited the production of TNF-alpha by the macrophages after induction by either LPS. These results suggested the following possibilities, i) the induction level of TNF-alpha by P. heparinolytica is similar to that of Salmonella minnesota, ii) tyrosine phosphorylation is not the only pathway for the TNF-alpha production induced by these LPSs, iii) different regulatory mechanisms are involved in TNF-alpha production in P. gingivalis LPS stimulated and P. heparinolytica LPS stimulated cells.

Animals↗

A hamster model of equine herpesvirus 9 induced encephalitis.

An acute and lethal infection of equine herpesvirus 9 (EHV-9), a new type of equine herpesvirus, was established in Syrian hamsters by intranasal inoculation. Clinical symptoms included the loss of body weight, nasal and ocular discharges and apparent neurological symptoms. Both LD50 and ID50 were equal at 33 plaque forming units. Histological and immunohistochemical examination demonstrated that the virus replicated in the olfactory mucosal cells and in the neurons of the olfactory bulbs, cerebrum and mesencephalon. The induction of encephalitis by intranasal but not by other routes of inoculation (i.v., i.p., i.m.) indicated that EHV-9 entered the brain via the olfactory nerve and then spread trans-synaptically to connecting neurons along the olfactory tract. This animal model should be useful for studying the pathogenesis and neurovirulence of this newly discovered neurotropic virus as well as other neurotropic herpesviruses.

Animals↗

Human pulmonary dirofilariasis presenting as a small nodule with a cavity.

A 73-year-old woman had a 4-year history of lung fibrosis from collagen vascular disease. She presented with a complaint of dry cough. A chest radiograph showed a 2-cm solitary pulmonary nodule with a small cavity in the right lower lobe. Preoperatively, we performed computed tomography of the chest and measured tumor markers. Video-assisted thoracotomy was performed because we could not rule out lung cancer. Pathologic analysis confirmed the presence of a granuloma with Dirofilaria immitis. In Japan, the incidence of human dirofilariasis has steadily increased and must be considered in the workup of cavitary pulmonary nodules.

Aged↗

A novel technique for myomectomy. Intranodal surgery with an electromechanical tissue borer.

OBJECTIVE: To investigate the possibility of clinical application of a new technique for myomectomy that involves morcellating the myoma within the myometrium with a new instrument that minimizes invasion of the myometrium and abdominal wall. STUDY DESIGN: In a pilot clinical study, myomectomy was performed on five women with uterine myomas and a normal menstrual cycle using a microwave coagulator and electromechanical tissue borer of our invention. The length of the surgical incisions in the abdominal wall and myometrium, operating time and blood loss were measured. RESULTS: The mean length of the surgical incisions was 6.3 cm in the abdominal wall and 3.5 cm in the myometrium. The mean operating time was 167 minutes, and the mean blood loss was 312 mL. The length of the incisions in the abdominal wall and myometrium per centimeter of the maximal diameter of the myoma was 0.78 and 0.42 cm, respectively. The incision tended to become smaller in successive operations. CONCLUSION: This new technique of myomectomy significantly reduced invasion of the abdominal wall and uterus.

Adult↗

Effects of a structured psychiatric intervention on immune function of cancer patients.

The aim of the present study was to examine the influence of mood state and coping styles on the immune function in Japanese breast cancer patients who participated in a structured group intervention program. The program consisted of five-weekly 90-minute sessions, including psycho-education, psychological support, problem-solving technique and relaxation/imagery. Out of 77 breast cancer patients who participated in this program, 34 were eligible for measurement of immune functions because they received adjuvant chemotherapy. Comparison of the pre- and post-intervention scores of the Profile of Mood States (POMS) revealed significant decreases in Depression (p < 0.05), Lack-of-Vigor (p < 0.01), Tension-Anxiety (p < 0.01), Confusion (p < 0.05) and Total Mood Disturbances (p < 0.01), as expected. Concerning coping styles, there were tendencies to decrease the score of active-cognitive coping (p = 0.09), although the differences were not statistically significant. In contrast, the pre- and post-intervention values of immune parameters such as CD3, CD4, CD8, CD4/8 and natural-killer cell activity showed no significant differences. In this report, we discuss several possibilities underlying these findings. Further studies with a larger number of subjects and controls are needed to reach conculusions.

Adaptation, Psychological↗

Effects of ethanol on neuronal migration and neural cell adhesion molecules in the embryonic rat cerebral cortex: a tissue culture study.

To investigate whether ethanol has direct effects on neuronal migration in the cerebral cortex, we performed a tissue culture study using embryonic rat brain with thymidine autoradiography. After we labeled progenitor cells in the ventricular zone of E16 cerebral cortex explants with [3H]thymidine, the explants were cultured for 48 h, and then distribution of labeled cells was evaluated autoradiographically. Adding 3.0 or 6.0 mg/ml ethanol to the culture medium caused significantly decreased distribution of labeled cells in the outer intermediate [control: 2.0+/-0.6% (mean+/-S.D.); 1.0 mg/ml ethanol: 2.1+/-1.5%; 3.0 mg/ml ethanol: 0. 5+/-1.5% (P<0.05); 6.0 mg/ml ethanol: 0.4+/-0.5% (P<0.05)] and the inner intermediate-A zones [control: 19.5+/-6.2%; 1.0 mg/ml ethanol: 13.1+/-8.6%; 3.0 mg/ml ethanol: 3.0+/-3.4% (P<0.01); 6.0 mg/ml ethanol: 5.2+/-2.9% (P<0.01)] compared to the control group. The mitotic index after 48-h culture was significantly reduced in the 6. 0 mg/ml ethanol group (0.260+/-0.114%; P<0.01) compared to the control group (0.600+/-0.158%). This suggests that ethanol inhibits neuronal migration in the cerebral cortex, although prolongation of the cell cycle by ethanol may contribute to the decreased number of labeled cells in the outer intermediate and inner intermediate-A zones. Furthermore, an abnormally dense and tortuous staining pattern of immunoreactive products of N-CAM was seen on the surface of migrating neurons in the 3.0 and 6.0 mg/ml ethanol groups, while the L1 staining pattern did not differ between the control and ethanol groups. These results suggest that abnormal expression of N-CAM may be involved in the inhibition of neuronal migration by ethanol.

Animals↗

Epstein-Barr virus (EBV)-infected cells were frequently but dispersely detected in T-cell lymphomas of various types by in situ hybridization with an RNA probe specific to EBV-specific nuclear antigen 1.

Association of Epstein-Barr virus (EBV) with T-cell lymphomas was examined by in situ hybridization (ISH) with an antisense probe specific to abundantly expressed EBV-encoded small RNA-1 (EBER1). In addition to EBER1, EBV-specific nuclear antigen-1 (EBNA-1) is commonly expressed in EBV-associated tumors and latently infected B-lymphocytes. We examined paraffin sections of T-cell lymphomas except those of nasal origin for expression of latent viral transcripts by ISH. Using ISH with improved antisense RNA probe specific to EBNA-1 mRNA, the virus was detected in 19 (59%) of 32 cases, whereas the EBER1 transcript was found in only 15 (47%) of 32 cases by conventional EBER-ISH, resulting in 21 EBV-positive cases (66%) by combining the two methods. Latent membrane protein 1 (LMP1) mRNA of EBV was detected in 15 of 32 cases (47%), while no EBNA2 expression was observed in any these tumors. Patients with these lymphomas positive for LMP1 expression showed lower survival rates than those without expression of the viral mRNA. These results indicate that, in addition to EBER-ISH, RNA-RNA ISH with EBNA1 probes could be useful for detection of EBV-infected cells in paraffin sections, and detection of LMP1 mRNA expression in tumor cells could be a useful prognostic factor for T-cell lymphoma.

Animals↗

A functional and quantitative mutational analysis of p53 mutations in yeast indicates strand biases and different roles of mutations in DMBA- and BBN-induced tumors in rats.

In order to analyze the mutational events and to understand the biological significance of the p53 gene in chemical carcinogenesis, we applied a new yeast-based p53 functional assay to ovarian tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA), as well as to transitional cell carcinomas of the urinary bladder induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats. The assay demonstrated that 15 of 19 DMBA induced tumors harbored clonal p53 mutations, which is consistent with the expectations of the "clonal expansion" hypothesis. The majority of the mutations were purine (AG) to pyrimidine (CT) transversions (12/19) on the non-transcribed (sense) strand (NTS), which is likely to be due to depurination created by DMBA adduct formation on the NTS. In contrast, we found no pyrimidine to purine [corrected] transversion on the NTS. After cessation of BBN treatment, BBN-induced multifocal lesions in the bladder contained heterogeneous p53 mutations at an early stage. In the later stage, however, clonal p53 mutations were identified in 4 out of 7 bladders analyzed, conforming with the concept of "field cancerization". The observed base substitutions were G-->A (1/6) or C -->T transitions (2/6), and mutations at T (3/6) on the NTS in clonal mutations, together with non-clonal mutations, showing a preference of C-->T to G-->A (17 vs. 0). Thus, preferential repair was found in the transcribed strand of the p53 gene, whether modified by DMBA or by BBN carcinogens. Very similar mutation patterns were observed between clonal and non-clonal mutations in the DMBA- and BBN-induced tumors, indicating that the rat yeast p53 functional assay can be a potential tool for the characterization of in vivo mutation patterns of p53, when modified by chemical carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

Differentiation of Coxiella burnetii isolates by sequence determination and PCR-restriction fragment length polymorphism analysis of isocitrate dehydrogenase gene.

The isocitrate dehydrogenase (icd) gene of Coxiella burnetii was cloned and sequenced to differentiate between isolates with various geographic origins and phenotypic properties. Based on the gene sequences all 19 isolates studied could be divided into three groups. Group 1 contained isolates originating from acute cases of Q fever, ticks and cows. Groups 2 and 3 included isolates from chronic Q fever patients and a prototype strain from an aborted goat. Although the icd gene profiles were different among isolates of the latter two groups, there were two base differences common for both groups which could be used as markers to distinguish them from group 1 isolates. Based on one of the markers a simple method using PCR-restriction fragment length polymorphism analysis was developed for rapid differentiation of C. burnetii isolates as well as for direct detection and differentiation of the bacterium in human serum samples. Taken together, the study results suggest that the icd-based differentiation method may be useful in clinical investigation of Coxiella infections.

Animals↗

Secretory IgA-mediated basophil activation. II. Roles of GTP-binding regulatory proteins and phosphatidylinositol 3-kinase.

Secretory IgA (sIgA) is the most abundant Ig isotype in mucous secretions in the upper and lower airways, where basophils exert effector functions during allergic inflammation. We recently demonstrated that immobilized sIgA on Sepharose beads is capable of inducing basophil degranulation ( approximately 15% of total histamine). To investigate the detailed mechanisms of this degranulation, we established in this study a new assay system for sIgA-mediated basophil activation. Immobilized sIgA on a plastic surface induced strong histamine release ( approximately 50% of total histamine) comparable to anti-IgE, and we analyzed the nature of basophil signal transduction by sIgA using various inhibitors. sIgA-induced basophil histamine release was inhibited completely by pertussis toxin, but anti-IgE-induced release was not affected. sIgA-mediated release was also inhibited by phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, wortmannin. These results strongly suggest that sIgA activates basophils via an IgE-independent novel mechanism involving both Gi protein and PI 3-kinase.

Basophils↗

Activation of mitochondrial ATP-sensitive K(+) channel for cardiac protection against ischemic injury is dependent on protein kinase C activity.

Protein kinase C (PKC) is involved in the second messenger signaling cascade during ischemic and Ca(2+) preconditioning. Given that the pharmacological activation of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels also mimics preconditioning, the mechanisms linking PKC activation and mitoK(ATP) channels remain to be established. We hypothesize that PKC activity is important for the opening of the mitoK(ATP) channel. To examine this, a specific opener of the mitoK(ATP) channel, diazoxide, was used in conjunction with subcellular distribution of PKC in a model of ischemia/reperfusion (I/R). Langendorff-perfused rat hearts were subjected to 40-minute ischemia followed by 30-minute reperfusion. Effects of activation of the mitoK(ATP) channel and other interventions on functional, biochemical, and pathological changes in ischemic hearts were assessed. In hearts treated with diazoxide, left ventricular end-diastolic pressure and coronary flow were significantly improved after I/R; lactate dehydrogenase release was also significantly decreased. The morphology was well preserved in diazoxide-treated hearts compared with nontreated ischemic control hearts. The salutary effects of diazoxide on the ischemic injury were similar to those of Ca(2+) preconditioning. Administration of sodium 5-hydroxydecanoate, an effective blocker of the mitoK(ATP) channel, or chelerythrine or calphostin C, an inhibitor of PKC, during diazoxide pretreatment or during continuous presence of diazoxide in the ischemic period, completely abolished the beneficial effects of the diazoxide on the I/R injury. Blockade of Ca(2+) entry during diazoxide treatment by inhibiting the L-type Ca(2+) channel with verapamil also completely reversed the beneficial effect of diazoxide during I/R. PKC-alpha was translocated to sarcolemma, whereas PKC-delta was translocated to the mitochondria and intercalated disc, and PKC-epsilon was translocated to the intercalated disc of the diazoxide-pretreated hearts. Colocalization studies for mitochondrial distribution with tetramethylrhodamine ethyl ester (TMRE) and PKC isoforms by immunoconfocal microscopy revealed that PKC-delta antibody specifically stained the mitochondria. ATP was significantly increased in the diazoxide-treated hearts. Moreover, the data suggest that activation and translocation of PKC to mitochondria appear to be important for the protection mediated by mitoK(ATP) channel.

Adenosine Triphosphate↗

Requirement of replication licensing for the dyad symmetry element-dependent replication of the Epstein-Barr virus oriP minichromosome.

Latent Epstein-Barr virus genome is maintained in cells by the viral oriP-binding factor EBNA1 and cellular replication factors. EBNA1 binds to the dyad symmetry (DS) element in oriP and initiates DNA replication once in a single S phase, but the mechanism by which this DS-dependent replication is initiated is unknown. Replication licensing of cellular chromatins occurs during early G1 phase. Because licensing is essential for the next round of replication in S phase, it facilitates once-in-a-cell-cycle replication of the cellular genome. Using the transient replication assay with HeLa/EB1 cell, we demonstrate that the oriP plasmid required a cell cycle window including early G1 phase for replication in the next S phase. The plasmid containing only the DS element had a similar requirement of early G1 phase for replication. Analysis using sucrose density gradient centrifugation revealed that the oriP minichromosome existed in two distinct states: one formed at late G1 and the other formed at G2/M. These results suggest that the DS-dependent DNA replication from oriP requires the replication licensing, implying a possible involvement of the cellular licensing factor MCM in the DNA replication from oriP.

Cell Cycle↗

Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3.

Previously, we mapped the novel CC chemokine myeloid progenitor inhibitory factor 2 (MPIF-2)/eotaxin-2 to chromosome 7q11.23 (Nomiyama, H., Osborne, L. R., Imai, T., Kusuda, J., Miura, R., Tsui, L.-C., and Yoshie, O. (1998) Genomics 49, 339-340). Since chemokine genes tend to be clustered, unknown chemokines may be present in the vicinity of those mapped to new chromosomal loci. Prompted by this hypothesis, we analyzed the genomic region containing the gene for MPIF-2/eotaxin-2 (SCYA24) and have identified a novel CC chemokine termed eotaxin-3. The genes for MPIF-2/eotaxin-2 (SCYA24) and eotaxin-3 (SCYA26) are localized within a region of approximately 40 kilobases. By Northern blot analysis, eotaxin-3 mRNA was constitutively expressed in the heart and ovary. We have generated recombinant eotaxin-3 in a baculovirus expression system. Eotaxin-3 induced transient calcium mobilization specifically in CC chemokine receptor 3 (CCR3)-expressing L1.2 cells with an EC(50) of 3 nM. Eotaxin-3 competed the binding of (125)I-eotaxin to CCR3-expressing L1.2 cells with an IC(50) of 13 nM. Eotaxin-3 was chemotactic for normal peripheral blood eosinophils and basophils at high concentrations. Collectively, eotaxin-3 is yet another functional ligand for CCR3. The potency of eotaxin-3 as a CCR3 ligand seems, however, to be approximately 10-fold less than that of eotaxin. Identification of eotaxin-3 will further promote our understanding of the control of eosinophil trafficking and other CCR3-mediated biological phenomena. The strategy used in this study may also be applicable to identification of other unknown chemokine genes.

Amino Acid Sequence↗