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Biomedical subjects

N Mori

Publications and source records attributed to N Mori.

At least 145 records · Page 8Linked to original sources

Lymphomatous features of aggressive NK cell leukaemia/lymphoma with massive necrosis, haemophagocytosis and EB virus infection.

AIMS: Aggressive natural killer (NK) cell leukaemia will be categorized as a distinct entity in the new WHO classification of malignant lymphomas. However, its non-leukaemic features remain unclear. We therefore investigated the morphological and immunophenotypic features of this lymphoma. METHODS AND RESULTS: Four cases with aggressive NK cell lymphoma were morphologically and immunohistochemically studied. All cases followed an aggressive course with death occurring within about 3 months of initial presentation. In these cases, the neoplastic cells disseminated throughout systemic lymph nodes and invaded various tissues and organs. The lymphoma cells were large cells showing nuclear irregularity and a pattern of sinusoidal invasion in lymph nodes. Apoptosis and coagulation necrosis were both frequently observed. Haemophagocytosis was observed in all cases. Neoplastic cells in paraffin-embedded tissue specimens from these patients had CD3(CD3epsilon)+ CD56(123C3)+ granzyme+ TIA-1+ EBERT+ CD43(MT1)- CD45RO(UCHL-1)- CD57(Leu7)- CD20(L26)- phenotypes. In the two cases where tissue was available for immunohistochemical study in frozen sections, neoplastic cells showed CD56(Leu19)+ perforin+ Fas ligand(FasL)+ CD2(Leu5b)- CD3(Leu4)- CD4(Leu3)- CD5(Leu1)- CD7(Leu9)- CD8(Leu2)- betaF1- TCRdelta1- phenotypes. CD16(Leu11b) was positive in one case. CONCLUSIONS: : Natural killer cell lymphomas appear to represent a non-leukaemic counterpart of aggressive natural killer cell leukaemia, a relationship similar to that in adult T-cell leukaemia/lymphoma. Awareness and diagnosis of this aggressive lymphoma is important because of its fulminant course.

Adult↗

Presence of B220 within thymocytes and its expression on the cell surface during apoptosis.

B220 is the full-length splicing isoform of a tyrosine phosphatase CD45 and is predominantly expressed as a transmembrane protein on B cells. Other splicing isoforms of CD45 are yielded by alternative splicing of exons 4, 5 and 6. Recently, the expression of B220 on peripheral T cells during activation-induced cell death has been reported. To investigate whether B220 is implicated in apoptosis of immature T cells, we analysed (by flow cytometry using the anti-B220 monoclonal antibody, RA3-6B2) the expression of B220 on mouse thymocytes undergoing X-irradiation- and dexamethasone (DEX)-induced apoptosis. The expression of B220 on thymocytes positive for Thy-1 was induced by X-irradiation or DEX treatment and increased with length of incubation. The expression of B220 was pronounced on the apoptotic hypodiploid cells in the fraction showing lower forward scattering values. Reverse transcription-polymerase chain reaction detected mRNA containing exons 4, 5 and 6 of CD45 in normal thymocytes as well as those exposed to X-rays or DEX. Surprisingly, cytoplasmic B220 antigens were detected in a considerable fraction of normal thymocytes. Moreover, the expression level of the 220 000-MW protein in normal thymocytes was similar to that in the thymocytes undergoing apoptosis. During apoptosis, the expression level of B220 antigen was reduced in the cytoplasm but, conversely, up-regulated on the surface of thymocytes. These results suggest that B220 is constitutively expressed as a cytoplasmic form within thymocytes and possibly translocated to the cell membrane during apoptosis.

Animals↗

Cosinor analysis of heart rate variability in ambulatory migraineurs.

OBJECTIVE: To clarify whether the circadian rhythm of heart rate variability parameters can be identified in patients with migraine during a headache-free period and to identify any specific pattern of the circadian rhythm of heart rate variability, using time-domain and spectral analysis and cosinor rhythm analysis of heart rate variability during normal daily activity. METHODS: Forty-eight-hour Holter electrocardiograms were recorded for 27 patients with migraine during headache-free periods and 24 healthy controls during free activity. The circadian rhythms of heart rate fluctuation parameters, that is, mean interval, standard deviation, root-mean-square successive differences (RMSSD), %RR50, and low (0. 020 to 0.150 Hz) and high frequency (0.150 to 0.400 Hz) heart rate fluctuations were analyzed with the group mean cosinor method. RESULTS: The group mean cosinor analysis and the acrophase-amplitude analysis demonstrated significant differences in circadian rhythm in SD, RMSSD, %RR50, and high frequency between the group with migraine and controls. The amplitudes of SD, RMSSD, %RR50, and high frequency in the group with migraine were smaller than those in controls, which implied parasympathetic hypofunction in migraineurs. There were no significant differences in the MESOR (midline estimating statistic of rhythms) of the analyzed heart rate parameters except for low frequency. The MESOR of low frequency in the migraineurs was significantly smaller than that in the controls. CONCLUSIONS: Patients with migraine have hypofunction in the parasympathetic nervous system during normal daily activity in the headache-free period.

Adolescent↗

Control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit by unselective use of nasal mupirocin ointment.

In September 1996, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization occurred in the neonatal intensive care unit (NICU) of our hospital. After failing to control the outbreak by conventional methods we implemented an intranasal blanket use programme of mupirocin ointment from the beginning of November 1997. In the programme, patients who had been carrying MRSA received intranasal administration of the ointment three times daily for the first three days and consecutively three times weekly, while newly admitted patients and those who had not been colonized were prophylactically medicated three times weekly. This blanket administration was executed for one month. Methicillin-resistant Staphylococcus aureus colonization became undetectable in all but one intubated inpatient who had already been colonized before the start of the programme, and no new acquisitions occurred until the middle of January 1998, seven weeks after the termination of the blanket use programme. The rate of colonized patients in the unit also decreased. During and after the programme, neither an increase in minimum inhibitory concentration for the antibiotic nor apparent adverse reactions in any of the treated patients were observed. We concluded that this procedure is an effective method of controlling an MRSA outbreak in an NICU when the outbreak cannot be managed with conventional measures.

Administration, Intranasal↗

Detection of telomerase activity in peritoneal lavage fluid from patients with gastric cancer using immunomagnetic beads.

Cytologic examination of peritoneal lavage fluid is a useful predictor of peritoneal recurrence in gastric cancer. However, this technique is not overly sensitive and requires special abilities in the cytologist. In this study, telomerase activity was used to detect free cancer cells in peritoneal lavage fluid from patients with gastric cancer. In the first part, 12 lavage-fluid samples obtained from 12 patients with gastric cancer were analysed using the conventional telomeric repeat amplification protocol (TRAP) assay. Three of five patients with early gastric cancer had positive telomerase activity. These false-positive results may have been due to lymphocyte contamination. Furthermore, polymerase chain reaction inhibitors were also detected in the lavage-fluid samples. Therefore, we developed a novel method for elimination of haematopoietic cell and Taq polymerase inhibitors to increase the accuracy of the TRAP assay using immunomagnetic beads, which bind to most normal and neoplastic human epithelial cells. Telomerase activity was found in 10 of 20 (50%) lavage-fluid samples from patients with serosal or subserosal invasion. Cytologic examination was positive in nine of 20 (45%) samples. Both the telomerase activity and cytology were negative in all 14 patients without serosal or subserosal invasion. These results suggest that the TRAP assay combined with immunomagnetic beads might be useful for detection of free cancer cells in the peritoneal space in gastric cancer without the aid of an experienced cytologist.

Adenocarcinoma↗

Local haemodynamic changes associated with neural activity in auditory cortex.

We used an optical technique to study haemodynamic changes associated with acoustically driven activity in auditory cortex of the chinchilla. Such changes are first detectable c. 0.5 s after stimulation, peak at 2-3 s, and decay within a further 3-6 s. This intrinsic signal imaging reveals activity in separate cortical areas, including primary auditory cortex (AI), secondary auditory cortex (AII) and an anterior auditory field (AAF). We have measured the timing of haemodynamics associated with each area, and find that AI has a different time course from AII and AAF; its haemodynamic change recovers more rapidly. We also show that within AI and AII, place specific activity related to acoustic stimulus frequency can be resolved by this optical imaging method. Our results show the close association between blood flow change and the local metabolic demands of neural activity. The data provide information about the potential of other functional imaging methods (e.g. PET, fMRI) which rely on activity related haemodynamic events.

Acoustic Stimulation↗

Long-term consumption of a methionine-supplemented diet increases iron and lipid peroxide levels in rat liver.

Methionine is a protective factor against various types of liver damage, but excessive dietary methionine is hepatotoxic. Because the mechanisms of L-methionine-related hepatotoxicity are poorly understood, the effect of long-term excessive L-methionine intake on the metabolism of iron and antioxidants was studied in rat liver to determine whether oxidative stress is involved. Wistar male rats were fed either an L-methionine-supplemented (16.0 g/kg) diet or a control diet for 1, 3, 6 and 9 mo. The growth rate of L-methionine-supplemented rats was significantly slower than that of controls. Iron, ferritin and thiobarbituric acid-reactive substances (TBARS) levels in the liver were greater in supplemented rats than in controls. Serum iron and transferrin levels were significantly lower in L-methionine-treated rats compared with controls. Serum ferritin did not differ between the two groups. Hepatic glutathione peroxidase activity, catalase activity and total glutathione concentrations were higher in rats fed the L-methionine-supplemented diet at 1 and 3 mo, but not at 6 and 9 mo. These results indicate that long-term consumption of excess L-methionine by rats may affect primarily iron metabolism rather than the antioxidant defense system and, consequently, induce an accumulation of iron.

Animals↗

Lennert's lymphoma: a variant of cytotoxic T-cell lymphoma?

We studied 10 cases of Lennert's lymphoma (lymphoepithelioid lymphoma) to evaluate the cellular origin of the neoplastic cells. There were six men and four women, aged 38 to 75 years (median, 56 yrs; mean, 59 yrs). The lymphoma cells tended to remain confined to lymph nodes, and extranodal involvement was rare. The mean overall survival was 42.2 months, which is relatively good compared with other peripheral T-cell lymphomas. Morphologically, the lymph node was occupied by small to large clusters of epithelioid cells interspersed with medium to large atypical lymphoid cells. In seven cases, large atypical lymphoid cells resembling Hodgkin's or Reed-Sternberg cells were observed. The phenotypes of these neoplastic cells were CD3+ CD4- CD8+ in five cases, CD3+ CD4+ CD8- in four cases, and CD3+ CD4- CD8- in one case. TIA-1 was positive by immunohistochemical staining in seven cases, whereas four cases were positive for granzyme B. Clonal rearrangement of the T-cell receptor gene was confirmed in all cases by either Southern blot hybridization or a polymerase chain reaction-based denature gradient gel electrophoresis method. Epstein-Barr virus was negative by in situ hybridization in all but one case. Lennert's lymphoma was formerly known as a CD4+ helper T-cell neoplasm. Our results suggest that, at least in some cases, the neoplastic cells are of cytotoxic T-cell origin.

Adult↗

Susceptibility to vancomycin of methicillin-resistant Staphylococcus aureus isolated in a university hospital in Japan.

Intravenous vancomycin was approved in 1991 in Japan and has been widely used for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Consequently, ever since the initial discovery of vancomycin intermediate-resistant S. aureus in Japan, the vancomycin resistance of this organism has been a great concern in clinical settings. We investigated whether vancomycin resistance had emerged in MRSA isolated in our hospital since the approval of the use of intravenous vancomycin. Vancomycin susceptibility was evaluated on the basis of minimum inhibitory concentrations determined by the agar dilution method and a heterogeneous resistance examination. The median minimum inhibitory concentration of the 69 MRSA strains isolated in 1988 and the 74 isolated in 1998 was 0.75 microgram/ml and 1.0 microgram/ml, respectively (p < 0.001), however, all of the strains were classified in the susceptible group. None of them was an MRSA heterogeneously resistant to vancomycin (hetero-VRSA), which has been defined as a strain having a 1/10(6) or greater heterogeneously resistant subpopulation to vancomycin. In another set of investigations, no hetero-VRSA were found among 12 other MRSA strains isolated after intravenous administration of vancomycin for 14 or more days (range: 14 to 77 days). We conclude that while the use of intravenous vancomycin may have slightly lowered the vancomycin susceptibility of MRSA in our hospital, the decrease in so small that it may not be significant clinically. In addition, no hetero-VRSA were found in our hospial.

Aged↗

Activation of intercellular adhesion molecule 1 expression by Helicobacter pylori is regulated by NF-kappaB in gastric epithelial cancer cells.

Interactions between leukocytes and epithelial cells may play a key role in Helicobacter pylori-associated gastric mucosal inflammation. This process is mediated by various cell adhesion molecules. The present study examined the molecular mechanisms leading to H. pylori-induced epithelial cell intercellular adhesion molecule-1 (ICAM-1; also called CD54) expression. Coculture of epithelial cells with cytotoxin-associated gene pathogenicity island-positive (cag PAI(+)) H. pylori strains, but not with a cag PAI(-) strain or H. pylori culture supernatants, resulted in upregulation of steady-state mRNA levels and cell surface expression of ICAM-1. Coculture with H. pylori induced an increase in luciferase activity in cells which were transfected with a luciferase reporter gene linked to the 5'-flanking region of the ICAM-1 gene. H. pylori activated the ICAM-1 promoter via the NF-kappaB binding site. An inducible nuclear protein complex bound to the ICAM-1 NF-kappaB site and was identified as the NF-kappaB p50-p65 heterodimer. H. pylori induced the degradation of IkappaB-alpha, a major cytoplasmic inhibitor of NF-kappaB, and stimulated the expression of IkappaB-alpha mRNA. Pretreatment of epithelial cells with pyrrolidine dithiocarbamate, which blocks NF-kappaB activation, inhibited H. pylori-induced ICAM-1 expression. THP-1 macrophagic cells, peripheral blood mononuclear cells, and purified neutrophils adhered to H. pylori-infected epithelial cells to a greater extent than to uninfected cells. These results show that H. pylori directly induces expression of ICAM-1 on gastric epithelial cells in an NF-kappaB-dependent manner that may support leukocyte attachment during inflammation.

Antineoplastic Agents↗

Hepatic microvascular responses to ischemia-reperfusion in low-density lipoprotein receptor knockout mice.

The overall objective of this study was to determine whether genetically induced hypercholesterolemia alters the inflammatory and microvascular responses of mouse liver to ischemia-reperfusion (I/R). The accumulation of rhodamine 6G-labeled leukocytes and the number of nonperfused sinusoids (NPS) were monitored (by intravital microscopy) in the liver of wild-type (WT) and low-density lipoprotein receptor-deficient (LDLr(-/-)) mice for 1 h after a 30-min period of normothermic ischemia. Plasma alanine transaminase (ALT) levels were used to monitor hepatocellular injury. Microvascular leukostasis as well as increases in NPS and plasma ALT were observed at 60 min after hepatic I/R in both WT and in LDLr(-/-) mice; however, these responses were greatly exaggerated in LDLr(-/-) mice. Pretreatment of LDLr(-/-) mice with gadolinium chloride, which reduces Kupffer cell function, attenuated the hepatic leukostasis, NPS, and hepatocellular injury elicited by I/R. Similar protection against I/R was observed in LDLr(-/-) mice pretreated with antibodies directed against tumor necrosis factor-alpha, intercellular adhesion molecule-1 (ICAM-1), or P-selectin. These findings indicate that chronic hypercholesterolemia predisposes the hepatic microvasculature to the deleterious effects of I/R. Kupffer cell activation and the leukocyte adhesion receptors ICAM-1 and P-selectin appear to contribute to the exaggerated inflammatory responses observed in the postischemic liver of LDLr(-/-) mice.

Alanine Transaminase↗

Clinical assessment of a new method for pacing pulse detection using a hybrid circuit in digital Holter monitoring.

Holter monitoring is widely used for the detection of arrhythmia and ischemic episodes. Traditionally, analog amplitude-modulated Holter devices have been used for detecting arrhythmia, but they produce signal distortion due to contour effects and phase distortion caused by the tape recorders. A digital Holter device without these disadvantages has been developed and can reproduce clinically accurate electrocardiographic waveforms useful for assessment of arrhythmia and ST segments. However, their reliability is questionable when detecting pacing pulses in pacemaker patients. Because electrocardiographic signals are digitized based on sampling rate, pacing pulses are occasionally missed. Therefore, the FM-300 was developed, a new device for detecting pacing pulses on digital recordings that has both digital and analog circuits in one system and indicates pacing pulse timing with arrows. This device can automatically detect and recognize pacing pulses from various artifacts and pacing modalities, making it easy to identify pacing pulses on digitally recorded electrocardiograms. The FM-300 is useful in the diagnosis and assessment of pacemaker function and has improved the reliability of pulse detection in digital Holter monitoring.

Artifacts↗

New members of a cold-responsive group-3 Lea/Rab-related Cor gene family from common wheat (Triticum aestivum L.).

A Cor (cold-responsive) cDNA that belongs to the group-3 Lea (late embryogenesis abundant)/Rab (responsive to abscisic acid, ABA) family was isolated from a winter-hardy cultivar of common wheat (Triticum aestivum L.). Screening of a cold-acclimated cDNA library was performed using an ABA- and other stress-responsive barley cDNA clone, Hva1, as a probe. A wheat cDNA clone (designated as Wrab19) putatively encoded a basic (pI = 10.3) and hydrophobic protein with 179 amino acids. The deduced protein showed characteristics of the group-3 LEA/RAB protein family. In contrast to the single copy barley Hva1, Wrab19 belonged to a multigene family in the hexaploid wheat genome and six loci were assigned to the homoeologous group 1 chromosomes. Using Wrab19 as a probe, four homologous cDNAs (designated as Wrab17) were isolated that encoded acidic (pI = 4.6-4.7) and hydrophobic proteins, all with 166 amino acids. The deduced proteins showed high homology (a mean of 84% identity) with a barley gibberellic acid (GA3)-inducible protein, ES2A, and several other group-3 LEA/RAB proteins. Wrab17 was considered to be a three-copy gene and each copy was assigned to chromosome 5A, 4B or 4D of hexaploid wheat. Transcripts of both Wrab19 and Wrab17 accumulated within 1 day of cold acclimation at 4 degrees C. They were responsive to ABA and/or GA3, but showed some cultivar differences in their response to these plant hormones. We conclude that the two genes are new members of the group-3 Lea/Rab-related Cor gene family in wheat.

Abscisic Acid↗

Nicotiana tabacum cDNAs encoding alpha and beta subunits of a heterotrimeric GTP-binding protein isolated from hairy root tissues.

Heterotrimeric GTP-binding proteins (G-proteins) play important roles in signal transduction pathways in eukaryotic cells. Through differential screening of a hairy root cDNA library of tobacco (Nicotiana tabacum L.) against transcripts from non-root tissues of normal cuttings, we obtained a partial cDNA clone that showed abundant expression and high homology to the alpha subunit gene of plant G-protein. After RACE-PCR, a full-length cDNA clone was obtained, which was 1,677-bp in length and contained an open reading frame encoding a protein of 384 amino acids. A cDNA clone encoding a beta subunit of G-protein was also isolated from the same cDNA library based on PCR amplification and library screening. The clone was 1,600-bp in length and contained an open reading frame encoding 377 amino acids. The deduced amino acid sequences of these clones showed high homology (75.5 to 99.8% amino acid identity) with alpha and beta subunits of other plant G-proteins. Genomic Southern blot analysis showed that the amphidiploid tobacco genome possessed two major copies of both alpha and beta subunit genes and some minor homologous copies. Northern blot analysis showed that the transcript of alpha subunit gene was abundant in the root tissues, particularly in the hairy root tissues. In contrast, the level of expression of the beta subunit gene was equivalent in all the tissues studied. Possible function of tobacco G-protein was discussed.

Amino Acid Sequence↗

A cold-responsive wheat (Triticum aestivum L.) gene wcor14 identified in a winter-hardy cultivar 'Mironovska 808'.

A cDNA library was constructed from a cold-acclimated winter-hardy common wheat (Triticum aestivum L.) cultivar 'Mironovska 808'. Using this library and a cold- and light-responsive barley cDNA clone cor14b as a probe, cDNAs of a homologous wheat gene wcor14 were isolated. Two identical cDNAs designated as wcor14a had an open reading frame encoding an acidic (pI = 4.71) and hydrophobic polypeptide with 140 amino acids (MW = 13.5 kDa). The deduced WCOR14a polypeptide showed 70% identity with the barley chloroplast-imported COR14b and had a nearly identical N-terminal, putative chloroplast transit peptide of 51 amino acid residues. Another cDNA clone wcor14b was assumed to encode a polypeptide WCORb which had 5 substitutions and a frame shift in the C-terminal region as compared with WCOR14a. RACE PCR, genomic PCR and Southern blot analyses suggested that wcor14 and its related sequences constitute a small multigene family with and without an intron in the hexaploid wheat genome. Northern blot analysis showed that transcripts of wcor14 accumulated within 3-6 hours of cold acclimation at 4 degrees C and the level reached a maximum at day 3. The transcripts became non-detectable within 3 hours after de-acclimation at room temperature. Contrary to the barley cor14b, a similar level of wcor14 transcripts was detected under the continuous darkness. Neither treatment with NaCl, ABA nor dehydration induced its expression. Based on these results we conclude that wcor14 is a wheat orthologue of the barley cor14b and specifically induced by low temperature.

Amino Acid Sequence↗