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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 163 records · Page 9Linked to original sources

Polymorphonuclear cells in chronic hemodialysis patients have intact phagocytotic and impaired bactericidal activities.

Although it has been well documented that chronic hemodialysis (HD) patients are highly susceptible to infectious diseases, the reasons for this have yet to be clarified. The present study was thus designed in order to better define this issue. Fifty-eight stable chronic HD patients without any evidence of infection were selected for the study. Blood samples were collected before and after HD from the same patient to determine the effect of HD. Reactive oxygen species (ROS) production in polymorphonuclear cells (PMNC) was measured by chemiluminescence using luminol. When the PMNC collected after HD were stimulated in vitro with a calcium ionophore (A23187), they produced a larger amount of ROS than that obtained from healthy volunteers [mean 7.4 x 10(5) photon counts (n = 58) vs. 3.0 x 10(5) photon counts (n = 17); p < 0.01]. A higher production of ROS after HD was seen in patients using membranes such as cellulose triacetate, polymethylmetacrylate and cellulose diacetate, whereas cuprophane did not seem to augment ROS production at all. On the other hand, when the PMNC after HD were stimulated with phorbol myristate acetate, their photon counts (mean 4.3 x 10(7)) were comparable to those before HD (mean 3.5 x 10(7)), and to those of PBMC obtained from healthy volunteers (mean 4.1 x 10(7)). It was thus suggested that the enhanced ROS production of PMNC was related to some stimuli, possibly even to the assay used to measure ROS. The phagocytotic activity and bactericidal effect of PBMC were measured by coculturing 1 x 10(5) PMNC with 1 x 10(5) CFU of Escherichia coli. Similar phagocytotic activities were noted in the PMNC from healthy volunteers and chronic HD patients before and after HD: the mean number of phagocytosed bacteria (log10 CFU) was 3.3, 3.3, and 3.3, respectively. However, in the case of a bactericidal effect, only the PMNC from healthy volunteers, but not the PMNC from HD patients, could effectively kill the bacteria, since the number of bacteria in PMNC decreased from 10(3.3) to 10(2.1). The PMNC from HD patients could not kill the bacteria-regardless of the characteristics of the membranes. It was thus concluded that the PMNC of chronic HD patients possess an intact phagocytotic activity which impaired bacterial killing, and was probably due to an abnormality occurring in the ROS production pathway.

Adult↗

A case of malignant lymphoma with hemophagocytic syndrome presenting as hepatic failure.

We report the case of a 50-year-old female with malignant lymphoma presenting hemophagocytic syndrome and liver failure. She developed high fever, marked jaundice, and progressive liver failure, followed by evidence of disseminated intravascular coagulation (DIC). The course was complicated by severe hepatitis and the patient died six days after admission. Pathological diagnosis on autopsy specimens of the lung hilar lymph nodes was non-Hodgkin's T cell lymphoma, of the diffuse small cell type. Histopathologic examination of the liver demonstrated diffuse liver cell destruction with prominent T lymphocyte infiltration in the portal and periportal area. In addition to marked lymphoma cell infiltration, hemophagocytosis by prominent infiltrative macrophages was observed in various organs, such as the liver and bone marrow, indicating the hemophagocytic syndrome. The hemophagocytic syndrome characterized in the present case may have been responsible for the extremely rapid and fulminant course.

Fatal Outcome↗

Flagellin gene diversity among Helicobacter pylori strains and IL-8 secretion from gastric epithelial cells.

BACKGROUND: To clarify the pathological functions of the virulence factors of Helicobacter pylori, a comparative analysis was carried out on the relationship between motility, flagellar gene polymorphism, vacuolating cytotoxin (VT) production and interleukin-8 (IL-8) induction. METHODS: Twenty-five strains were examined for restriction fragment length polymorphism (RFLP) of the flagellin gene. Motility was measured using semisolid agar plates. Cytotoxicity was assayed using RK-13 cells. IL-8 secretion was assessed by the enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: H. pylori was classified into four groups according to their flagellar RFLP. No differences were noted in motility or VT production among the four groups, but a significant difference was noted in IL-8 induction. In addition, highly motile strains produced more IL-8. CONCLUSION: This flagellar genetic polymorphism may be associated with IL-8 induction.

Animals↗

Three-dimensional kinematics of the human knee with intracortical pin fixation.

Knee motion was measured with an instrumented spatial linkage (accuracy, linear +/-500 microns; angular, +/-0.5 degree) fixed with intracortical Kirschner wires in five healthy male volunteers (five knees, judged clinically to be normal). This technique allows an accurate description of the relative angular and linear movements between tibia and femur without the effect of skin movement relative to the bone and without the effect of changing muscle volume. Motion of the tibia relative to the femur was described in terms of three clinically meaningful rotations and three translations between full extension and 60 degrees flexion: (1) abduction and adduction: 3.4 degrees +/- 1.2 degrees; (2) internal and external rotation: 10.6 degrees +/- 2.8 degrees, representing screw home motion; (3) anterior and posterior: 5.2 +/- 1.7 mm, representing roll back phenomenon; (4) proximal and distal: 1.2 +/- 2.7 mm; and (5) medial and lateral: 1.1 +/- 2.6 mm.

Adult↗

Induction of apoptosis by calmodulin-dependent intracellular Ca2+ elevation in CD4+ cells expressing gp 160 of HIV.

Human CD4+ cell clones expressing either gp160 or gp120 of HIV-1 under the transcriptional control of an inducible promoter were used to examine the role of Ca2+ signalling in the induction of apoptosis by envelope glycoproteins. Singlecell killing with apoptosis was induced in the cells expressing gp 160 while no such apoptosis was found in the cells expressing gp 120. An increase of intracellular Ca2+ was found in the gp 160-expressing cells but not in the gp 120-expressing cells as determined by Intracellular Ca2+ imaging analysis before the appearance of DNA fragmentation. W7, a calmodulin antagonist, blocked the elevation of Ca2+ as well as the resultant DNA fragmentation, which thus implies that the calmodulin-dependent intracellular Ca2+ release system is first activated by gp 160 and thereafter apoptosis takes place. The above results thus indicate that Ca2+ signalling plays a crucial role in the apoptosis accompanying the single-cell death induced by gp 160 in CD4+ cells.

Apoptosis↗

Protection of isolated lung from reperfusion injuries by rinsing with high colloidal osmotic solution with deferoaxmine.

We examined the efficacy of rinsing isolated lungs subjected to prolonged hypothermic storage with a high colloidal osmotic pressure solution prior to ex vivo blood reperfusion in order to preserve physiologic functions, suppress peroxidation of mitochondrial membranes, and inhibit infiltration of neutrophils. Isolated rabbit lungs were flushed with a Rinse-1 solution (289 mOsm/kg H2O) to remove remaining blood and immersed in physiologic saline at 8 degrees C for 24 hr. The control group received blood reperfusion immediately after storage; the Rinse-1 group was rinsed with Rinse-1 solution before blood reperfusion and the Rinse-2 group with Rinse-2 solution (312 mOsm/kg H20) including deferoxamine. Reperfused blood was passed through an artificial membranous lung to reduce oxygen tension (PO2) to the venous level, and time-dependent changes in airway pressure (AWP), pulmonary artery pressure (PAP), and PO2, as a measure of gas-exchange capability were examined. We estimated the lipid peroxide level in mitochondrial membranes as thiobarbituric acid-reactive substances (TBARS), i.e., malonedialdehyde, and neutrophil infiltration into lung tissue by measuring myeloperoxidase activity after 60 min of blood reperfusion. The PO2 was significantly higher in both rinsed groups compared with the control, while neither AWP nor PAP was significantly different in the three treatment groups. Both mitochondrial TBARS and myeloperoxidase activity were significantly higher in the control group compared with either rinsed group. These results indicate that rinsing stored lungs with a solution of high colloidal osmotic pressure prior to blood reperfusion was effective in preserving physiologic function and inhibiting neutrophil infiltration. Addition of deferoxamine was markedly effective in reducing TBARS formation and lessening reperfusion injury of stored lungs.

Animals↗

Extracellular ATP activates mast cells via a mechanism that is different from the activation induced by the cross-linking of Fc receptors.

In this study, the extracellular ATP (ATPo)-induced biochemical events were elucidated by comparing them with either the Fc epsilon RI- or Fc gamma R-induced events in the mouse mast cell line MC9. The omission of extracellular Ca2+ almost completely abolished the elevation of intracellular Ca2+ ([Ca2+]i) in the ATPo-stimulated cells, but only suppressed the second phase of the increase of [Ca2+]i in FcR-stimulated cells, thus suggesting that the ATPo-induced elevation of [Ca2+]i is totally dependent on the entry of extracellular Ca2+. Pretreatment with genistein, which inhibits protein kinases, especially protein tyrosine kinase, inhibited the FcR-triggered increase of [Ca2+]i, but not the ATPo-triggered one; however, such pretreatment did suppress both ATPo- and FcR-mediated beta-hexosaminidase release. An immunoblot analysis revealed that both ATPo and the cross-linking of FcRs led to tyrosine phosphorylation of 44- and 110-kDa proteins, which thus suggested that these tyrosine-phosphorylated proteins are involved in a modulation of the degranulation process following an elevation of [Ca2+]i. Pretreatment with PMA inhibited the FcR-induced [Ca2+]i increase, while not inhibiting the ATPo-induced one, thus suggesting that ATPo can mobilize [Ca2+]i even when protein kinase C (PKC) has already been activated. Pretreatment of calphostin C, a specific PKC inhibitor, had little effect on the ATPo-mediated beta-hexosaminidase secretion, thus indicating that the ATPo-induced degranulation is not mediated by PKC. Taken together, these results demonstrate that ATPo activates MC9 mast cells by a mechanism that is different from the activation induced by the cross-linking of FcRs.

Adenosine Triphosphate↗

Biologic characteristics of esophageal epithelial dysplasia assessed by proliferating cell nuclear antigen.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) correlates with the cell proliferative state. Using a PCNA specific monoclonal antibody, various malignant neoplasms have been assessed for cell proliferation and malignant potential. However, there are few studies regarding the expression of PCNA in esophageal dysplasia. METHODS: PCNA expression was immunohistochemically determined in resected specimens from 27 patients with superficial esophageal carcinoma that contained areas with various degrees of dysplasia, carcinoma in situ (CIS), and carcinoma invading the mucosal layer. The authors estimated the cell proliferative activity and biologic characteristics of the basal and parabasal cells of these esophageal epithelial disorders. RESULTS: The degrees of PCNA labeling index (PCNA LI) of the basal layers were lower than those of the parabasal layers in normal epithelium and dysplastic lesions, respectively, whereas no difference in CIS was recognized between the two layers. The proportion of PCNA LI in the basal layer of moderate dysplasia was lower than that in the basal layer of severe dysplasia. Conversely, there were no statistical differences between severe dysplasia and CIS in both basal and parabasal layers. In terms of lymphocytic infiltration beneath the dysplasia, there was a close relationship between the degree of lymphocytic infiltration and the PCNA index of the basal and parabasal layers. CONCLUSIONS: PCNA expression may be a useful marker to reflect the biologic characteristics of esophageal dysplasia, suggesting that a high grade of dysplasia is as serious a lesion as esophageal carcinoma.

Biomarkers↗

Mitochondrial DNA and RNA processing in MELAS.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a maternally inherited disorder, is usually associated with a point mutation in mitochondrial DNA (mtDNA) at position 3,243 in the tRNA Leu(UUR) gene. To further study the pathogenesis of MELAS, we analyzed tissues from 8 MELAS-3,243 patients. Southern blot analysis showed an increase in the ratio of mtDNA to nuclear DNA in almost all tissues examined, implying that mitochondrial proliferation is ubiquitous and is not confined to ragged-red fibers in muscle. By northern blot analysis, we demonstrated increased steady-state levels of RNA 19, a polycistronic transcript corresponding to the 16S rRNA + tRNA Leu(UUR) + ND1 genes (which are contiguous in the mtDNA) in heart, kidney, and muscle. These results provide further evidence that altered mitochondrial nucleic acid metabolism may have pathogenic significance in MELAS.

Adult↗

DNA typing of HLA class II genes in Japanese patients with rheumatic heart disease.

To study further the association between HLA and rheumatic valvular disease, DNA typing HLA class II genes (DRB1, DQA1, DQB1 and DPB1) was performed in 72 unrelated Japanese patients with predominant mitral stenosis and 525 unrelated Japanese healthy controls, based on the polymerase chain reaction in combination of dot-blot hybridization with sequence-specific oligonucleotide probes. As compared with controls. Patients with mitral stenosis showed increased frequencies of DQA1*0104 (18.1% v 7.2%; RR = 2.82, P = 0.002, Pc = 0.03) and DQB1*05031 (13.9% v 4.8%: RR = 3.23, P = 0.002, Pc = 0.05). In contrast, no significant deviation in the frequencies of DRB1, DPA1 or DPB1 alleles was observed in the patients. These observations suggest that the susceptibility to mitral stenosis is in part controlled by a gene (or genes) in close linkage disequilibrium with HLA-DQA1*0104 and DQB1*05031, i.e. the susceptibility gene may be mapped within the HLA-DQ region.

Adult↗

Development of a de novo tumorous necrotic lesion in the liver after transcatheter arterial embolization combined with iodized oil infusion: report of a case.

We report herein the case of a 69-year-old woman in whom a hepatic tumorous necrotic lesion was discovered following transcatheter arterial embolization combined with iodized oil infusion (Lp-TAE) for a hepatoma. The lesion, which had not been evident prior to the Lp-TAE, was resected and analyzed pathologically. The portal area distribution in the necrotic lesion was the same as that in the surrounding hepatic tissue, suggesting that the lesion was derived from the nonneoplastic hepatic tissue. Moreover, extensive wall thickening and obstruction were observed in the intrahepatic portal vein and hepatic artery. These findings suggest that the lesion was a focus of hepatic infarction triggered by Lp-TAE.

Aged↗

Successful treatment of bronchial mucoepidermoid carcinoma in an 11-year-old boy by bronchoplasty: report of a case.

We report herein the rare case of an 11-year-old boy in whom mucoepidermoid carcinoma of the right upper lobe bronchus was successfully treated by bronchoplasty. The patient underwent bronchoscopy to investigate the cause of relapsing respiratory infections over the past 2 years, which revealed a tumor at the orifice of the right upper lobe bronchus. Thus, a right upper sleeve lobectomy was effectively carried out, preserving right pulmonary function. The tumor was observed to partially invade the bronchial wall, but not the lung parenchyma. Histological examination confirmed a diagnosis of mucoepidermoid carcinoma, classified as grade 2 by Conlan's classification. The patient has been well and free of recurrence for 3 years postoperatively.

Anastomosis, Surgical↗

An event-related potential study on the impairment of automatic processing of auditory input in schizophrenia.

Mismatch negativity (MMN) and P300 to auditory stimuli was carried out using global field power (GFP) in 25 schizophrenics and 25 normal controls. The peak latencies of MMN and P300 were significantly longer in schizophrenics than in normal controls, and the differences in MMN were marked in the frontal regions. The peak amplitudes of MMN and P300 were significantly smaller in schizophrenics. The scalp distribution of MMN to 1050 Hz tone differed between the two groups, although that to 1100 Hz was similar to each other. The results indicate an impairment in the automatic discrimination process of auditory input in schizophrenics.

Acoustic Stimulation↗

Lactoferrin-mediated protection of the host from murine cytomegalovirus infection by a T-cell-dependent augmentation of natural killer cell activity.

The administration of bovine lactoferrin (LF) with 1 mg/g body weight before the murine cytomegalovirus (MCMV) infection completely protected the BALB/c mice from death due to the infection. In these LF-treated mice, a significant increase in the activity was found in the NK cells but not in the cytolytic T lymphocytes which recognized an MCMV-derived peptide. Moreover, the elimination of the NK cell activity by an injection with anti-asialo GM1 antibody abrogated such augmented resistance, thus supporting the hypothesis that the LF-mediated antiviral effect in vivo is performed through the augmentation of NK cell activity. No such LF-mediated antiviral effect in vivo with the increased NK cell activity was found in athymic nude mice, whereas it was restored completely by the transfer of splenic T cells from LF-treated donors. These findings therefore suggest that T lymphocytes induce both the augmentation of NK cell activity and the resultant antiviral effect in the LF-treated hosts.

3T3 Cells↗