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Biomedical subjects

K Matsuo

Publications and source records attributed to K Matsuo.

At least 145 records · Page 8Linked to original sources

Induction of innate immunity by nasal influenza vaccine administered in combination with an adjuvant (cholera toxin).

Inactivated influenza vaccine was administered intranasally to BALB/c mice together with an adjuvant (cholera toxin B subunit [CTB] supplemented with a trace amount of the whole toxin, CTB*) and its ability to induce innate immunity and confer protection against influenza was examined. Nasal wash virus titres 3 days after inoculation of homologous viruses were measured as an index of the ability of the vaccine to confer protection in mice immunized with either CTB*-combined vaccine or CTB* alone 1-21 days previously. The results were as follows. (1) Partial but significant reduction of the nasal-wash virus titres (prevention) was detected beginning 3 days after the vaccination, that is, 2 days earlier than the appearance of both virus-specific antibody-forming cells (AFCs) in the nasal-associated lymphoid tissue (NALT) and virus-specific IgA antibody responses in the nasal washes of mice immunized with the CTB*-combined vaccine. (2) The protection, detected on day 3 and peaking on day 5 but lost by day 21, was also conferred in mice immunized with CTB* alone. (3) The non-specific prevention was detected at doses of more than 0.3 microg of CTB*/mouse. (4) The nonspecific protection beginning 3 days after the immunization involved the enhanced expression of cytokine mRNAs (IL-15 and IL-18), considered responsible for natural killer (NK) cell activation, by the non-T cell populations in the NALT. (5) Normal NALT cells, when cultured in vitro with CTB*, secreted IL-1beta within a few hours in culture. These results demonstrate that the CTB*-combined vaccine, when given intranasally into mice, can confer nonspecific protection against influenza beginning 3 days after the vaccination and that CTB* also possessed this ability to confer protection non-specifically and temporarily by inducing the secretion of IL-1beta, one of the most important cytokines that initiates both innate and adaptive immunity, and also NK cell activity.

Adjuvants, Immunologic↗

Genetic resistance to chemical carcinogen-induced preneoplastic hepatic lesions in DRH strain rats.

DRH strain rats were established by inbreeding a closed colony of Donryu rats continuously fed the chemical hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene for over 10 years. They are highly resistant to chemical induction of liver cancer and preneoplastic lesions. We studied the genetic basis of DRH resistance to preneoplastic lesions by analyzing 108 (F344 x DRH)F2 male rats fed 3'-methyl-4-dimethylaminoazobenzene for 7 weeks. Five parameters of preneoplastic liver lesions were selected for quantitative analysis: (a) number of glutathione S-transferase placental form-positive foci per unit area of liver section; (b) percentage area occupied by the foci; (c) average size of foci; (d) glutathione S-transferase placental form mRNA level; and (e) gamma-glutamyltranspeptidase mRNA level. Furthermore, O6-methylguanine DNA methyltransferase and mannose 6-phosphatase/insulin-like growth factor 2 receptor mRNA levels were quantified. Composite interval mapping analysis showed that there were two remarkably significant clusters of quantitative trait loci affecting preneoplastic liver lesions on chromosomes 1 and 4. These clusters were designated collectively as Drh1 and Drh2, respectively. The functions of the recessive DRH allele of Drh1 and the semidominant DRH allele of Drh2 were to suppress the phenotypes of precancerous lesions. Each cluster showed two to three subpeaks in linkage likelihood plots, suggesting the presence of several closely linked quantitative trait loci affecting preneoplastic lesions. Possible candidate genes at each locus will be discussed. Expression of O6-methylguanine DNA methyltransferase and mannose 6-phosphatase/insulin-like growth factor 2 receptor did not affect DRH resistance to hepatocarcinogenesis, although they were polymorphic between DRH and F344 rats.

Alleles↗

Development and sexual maturation of Echinococcus vogeli in an alternative definitive host, Mongolian gerbil (Meriones unguiculatus).

An alternative definitive host model for Echinococcus vogeli was developed using Mongolian gerbils. The animals treated with prednisolone tert-butylacetate were orally inoculated with protoscoleces of E. vogeli and the development of worms in the small intestine was observed until 50 days post infection (DPI). The parasites were recovered most frequently from the anterior part of the small intestine. The band formation (the sign of proglottisation) of the worm was observed at 7 DPI, the second proglottid and tests formation at 14 DPI, spermatozoa in seminal receptacle and cleavage of ova in uterus at 21 DPI, the hook formation of oncospheres at 28 DPI and the embryophore formation at 34 DPI. Eggs in the feces were first detected at 35 DPI. The coproantigen detection method developed for E. multilocularis could detect the E. vogeli coproantigen early in the infection, at 7 DPI during the prepatent period. Therefore, this technique could be used for the diagnosis of E. vogeli, replacing ordinary fecal egg examination.

Animals↗

The effects of listening comprehension of various genres of literature on response in the linguistic area: an fMRI study.

Using fMRI at a static magnetic field strength of 1.5T, we investigated how comprehension and humor of sentences would correlate to activation of the language areas in listening comprehension of a native language. Sentences with a high comprehension score augmented activation in the left inferior parietal lobule and posterior part of the left superior temporal gyrus, which may be related to semantic processing. Sentences with a high humor score induced activation in Broca's area, which may be associated with syntactic processing and auditory working memory. Furthermore, sentences with a high humor factor and/or a low comprehension score activated the middle frontal gyrus, which may be attributed to auditory working memory.

Adult↗

Cytokine mRNAs in the nasal-associated lymphoid tissue during influenza virus infection and nasal vaccination.

Intranasal immunization with a current inactivated influenza vaccine together with an adjuvant (cholera toxin B subunit supplemented with a trace amount of whole toxin, CTB*) was confirmed in BALB/c mice to mimic influenza virus (A/PR/8/34, H1N1) infection with respect to mucosal IgA antibody responses, in which IgA antibody-forming cell responses in the nasal-associated lymphoid tissue (NALT) were involved with a peak around 7 days after infection or vaccination. Next, the expression of various cytokine mRNAs in the NALT was compared in mice either infected with viruses or immunized with CTB*-combined vaccine, to examine Th cell and cytokine regulation of mucosal IgA antibody responses. In infected mice, strong IL-2, weak IL-4, strong IL-6 and strong IFN-gamma mRNA expressions were induced during early days of infection; especially, IFN-gamma mRNA was expressed by both CD4(+) and CD8(+) T cells around 7 days after infection. In mice given CTB*-combined vaccine, weak IL-2, strong IL-4, strong IL-6 and weak IFN-gamma mRNA expressions were induced during early days of vaccination; especially, IL-4 mRNA was expressed by CD4(+) T cells. Thus, IL-6 mRNAs were expressed strongly in both infected and vaccinated mice. The IFN-gamma-rich cytokine mRNA profiles in the infected mice were reflected upon serum IgG2a-rich Ab responses, while the IL-4-rich profiles in the vaccinated mice were reflected upon the IgG1-rich Ab responses. Thus, influenza virus infection and CTB*-combined nasal vaccine induced Th1 dominant and Th2 dominant cytokine profiles, respectively, while the similarity of mucosal IgA antibody responses between infection and vaccination could be explained by the appearance of IL-6 mRNAs.

Administration, Intranasal↗

Relation between spatial distribution of late potentials and location of origin of premature ventricular complexes on body surface map in patients with postinfarction ventricular tachycardia.

We studied the relationship between the spatial distribution of late potentials (LPs) and the origin of premature ventricular complexes (PVCs) using body surface maps in 55 patients with postinfarction sustained ventricular tachycardia (VT). Body surface maps were recorded from 87 leads to construct departure maps during sinus rhythm and signal-averaged ECGs were recorded from 32 unipolar leads to construct a LP map. The root-mean-square values during 40 ms intervals behind the QRS end were computed as LPs. The PVC map was recorded simultaneously in 14 patients presenting PVC with similar morphology to VT during LP detection. The origin of PVC was localized at the site of isopotential minimum when the potential exceeded -0.5 mV during the early QRS period. The LP area and the departure area showed a similar distribution. However, the PVC origin was closer to the site of LP maximum than the departure minimum in 11 (79%) patients, and the spatial correlation between the LP maximum and the PVC origin was good in 12 (86%) patients. LP and PVC mapping from the body surface is feasible and of worth to predict noninvasively the site of origin of ventricular arrhythmias in patients with remote myocardial infarction and sustained VT.

Adult↗

Treatment of noninvasive carcinoma: fifteen-year results at the National Cancer Center Hospital in Tokyo.

The introduction of screening mammography (MMG) will lead to increased detection of preclinical early breast cancer in Japan. It has become more important to understand the nature of these lesions. We tried to elucidate the long term prognosis and clinical and pathological characteristics of noninvasive cancers. A total of 336 (5.4%) ductal carcinoma in situ (DCIS) and 32 (0.5%) lobular carcinoma in situ (LCIS) were diagnosed in 6 277 breast carcinomas at the National Cancer Center Hospital from 1962 to 1995. Most (80%) LCIS occurred in premenopausal women. LCIS has significantly higher bilaterality than that of DCIS. Local recurrence occurred in approximately 10% of patients after breast conserving surgery for DCIS and LCIS. Four patients died of breast carcinoma, which were initially diagnosed as noninfiltrating carcinoma. The 15-year cause specific survival rates of patients with DCIS and LCIS were 98.5 % and 100 %, respectively.

Breast Neoplasms↗

The mitochondrial DNA of Dictyostelium discoideum: complete sequence, gene content and genome organization.

We present an overview of the gene content and organization of the mitochondrial genome of Dictyostelium discoideum. The mitochondria genome consists of 55,564 bp with an A + T content of 72.6%. The identified genes include those for two ribosomal RNAs (rn1 and rns), 18 tRNAs, ten subunits of the NADH dehydrogenase complex (nad1, 2, 3, 4, 4L, 5, 6, 7, 9 and 11), apocytochrome b (cytb), three subunits of the cytochrome oxidase (cox1/2 and 3), four subunits of the ATP synthase complex (atp1, 6, 8 and 9), 15 ribosomal proteins, and five other ORFs, excluding intronic ORFs. Notable features of D. discoideum mtDNA include the following. (1) All genes are encoded on the same strand of the DNA and a universal genetic code is used. (2) The cox1 gene has no termination codon and is fused to the downstream cox2 gene. The 13 genes for ribosomal proteins and four ORF genes form a cluster 15.4 kb long with several gene overlaps. (3) The number of tRNAs encoded in the genome is not sufficient to support the synthesis of mitochondrial protein. (4) In total, five group I introns reside in rnl and cox1/2, and three of those in cox1/2 contain four free-standing ORFs. We compare the genome to other sequenced mitochondrial genomes, particularly that of Acanthamoeba castellanii.

Animals↗

Dose dependency of prednisolone tertiary-butylacetate (PTBA) treatment on the establishment and site predilection of Echinococcus multilocularis in an alternative definitive host model using Mongolian gerbil (Meriones unguiculatus).

Mongolian gerbils (Meriones unguiculatus) were orally inoculated with 10,000 protoscoleces of Echinococcus multilocularis per head after being divided into five groups (A E). Each group was dosed with prednisolone tertiary-butylacetate (PTBA) as follows: A, 0 mg; B, 0.5 mg; C, 2 mg; D, 5 mg; and E, 10 mg/head. All animals were injected subcutaneously with control solvent or PTBA every other day from 6 days pre- to 6 days post-infection. Autopsy was performed at 7 days post-infection. Doses of PTBA and the number of worms recovered showed a positive correlation (r = 0.929, P < 0.0001). In groups A, B and C, the predilection site of the worms in the small intestine could not be determined, while in group D the worms were found more in the anterior part. In group E, the predilection site was the anterior part, followed by the middle and the posterior parts of the small intestine (Fisher's test: P < 0.01). The number of worms recovered from the anterior and the middle part of the small intestine also correlated positively with PTBA dose (anterior part: r = 0.930, P < 0.0001, middle part: r = 0.917, P < 0.0001). All groups of the PTBA-treated animals showed significant loss of weight compared to the nontreated animals (P < 0.01).

Animals↗

Synchronous multiple primary cancers of the stomach and duodenum in aged patients: report of two cases.

We describe herein the cases of two aged patients found to have synchronous multiple primary cancers of the stomach and duodenum. The first patient was an 82-year-old man who was preoperatively diagnosed as having gastric cancer after presenting with signs of pyloric stenosis. At laparotomy, duodenal cancer was incidentally found to have infiltrated the transverse colon. A pancreatoduodenectomy and right hemicolectomy with radical lymph node dissection was performed. Two early well-differentiated adenocarcinomas of the stomach and an advanced poorly differentiated adenocarcinoma of the duodenum were confirmed. This patient is now well without any evidence of recurrence more than 5 years after surgery. The second patient was a 77-year-old man who was also diagnosed as having gastric cancer after presenting with signs of pyloric stenosis. Preoperatively, duodenal cancer was detected by endoscopy. A pancreatoduodenectomy and partial colectomy with radical lymph node dissection was performed because the duodenal cancer was suspected of having infiltrated the transverse colon. An early moderately differentiated adenocarcinoma of the stomach and an advanced moderately differentiated adenocarcinoma of the duodenum were confirmed, but the duodenal cancer was not seen to invade the transverse colon microscopically. This patient died of cancer 7 months after surgery. Because multiple primary cancers commonly develop in elderly patients, a precise preoperative diagnosis must be made and optimal treatment applied.

Adenocarcinoma↗

Post-stimulus response in hemodynamics observed by functional magnetic resonance imaging--difference between the primary sensorimotor area and the supplementary motor area.

The blood oxygen level dependency (BOLD) contrast is a useful tool for functional neuroimaging based on the hemodynamic response to neuronal activation. We observed different hemodynamic responses in the BOLD signal between the primary sensorimotor area (SM1) and the supplementary motor area (SMA) in the sequential finger movement task. In the SMA, a stronger initial overshoot and a post-stimulus overshoot were observed. It was hypothesized from the time course analysis that the stronger initial overshoot reflected the activation of the SMA for motor control programming in the initial phase. Although the post-stimulus overshoot may be partially explained by cerebral blood flow (CBF) cerebral blood volume (CBV) uncoupling, its mechanism remained unknown. In the SM1, only the initial overshoot was observed and the level of BOLD signal was almost constant after the initial overshoot during the task period. These observations suggested that the BOLD signal is characterized by both CBF-CBV uncoupling and the neuronal activation characteristics in each region.

Adult↗

Dissociation of writing processes: functional magnetic resonance imaging during writing of Japanese ideographic characters.

Dissociation between copying letters and writing to dictation has been reported in the clinical neuropsychological literature. Functional magnetic resonance imaging (fMRI) was conducted in normal volunteers to detect the neurofunctional differences between 'copying Kanji', the Japanese ideographic characters, and 'writing Kanji corresponding to phonological information'. Four tasks were conducted: the copying-Kanji task, the writing-Kanji-corresponding-to-phonogram task, the Kanji-grapheme-puzzle task, and the control task. The right superior parietal lobule was extensively activated during the copying-Kanji task (a model of the copying letters process) and the Kanji-grapheme-puzzle task. These observations suggested that this area was involved in referring the visual stimuli closely related to the ongoing handwriting movements. On the other hand, Broca's area, which is crucial for language production, was extensively activated during the writing-Kanji-corresponding-to-phonogram task (a model of the writing-to-dictation process). The Kanji-grapheme-puzzle task activated the bilateral border portions between the inferior parietal lobule and the occipital lobe, the left premotor area, and the bilateral supplementary motor area (SMA). Since the Kanji-grapheme-puzzle task involved manipulospatial characteristics, these results suggested cooperation between visuospatial and motor executive functions, which may be extensively utilized in demanding visual language processing. The neurofunctional difference between 'copying Kanji' and 'writing Kanji corresponding to phonogram' was efficiently demonstrated by this fMRI experiment.

Adult↗

JunD protects cells from p53-dependent senescence and apoptosis.

JunD is the most broadly expressed member of the Jun family and the AP-1 transcription factor complex. Primary fibroblasts lacking JunD displayed p53-dependent growth arrest, upregulated p19(Arf) expression, and premature senescence. In contrast, immortalized cell lines lacking JunD showed increased proliferation and higher cyclinD1 levels. These properties are reminiscent of the effects of oncogenic Ras expression on primary and established cell cultures. Furthermore, JunD(-/-) fibroblasts exhibited increased p53-dependent apoptosis upon ultraviolet irradiation and were sensitive to the cytotoxic effects of TNF-alpha. The antiapoptotic role of JunD was confirmed using an in vivo model of TNF-mediated hepatitis. We propose that JunD protects cells from senescence, or apoptotic responses to stress stimuli, by acting as a modulator of the signaling pathways that link Ras to p53.

3T3 Cells↗

Osteoclast lineage commitment of bone marrow precursors through expression of membrane-bound TRANCE.

Osteoclast formation from hemopoietic precursors is induced by TRANCE (also called RANKL, ODF, and OPGL), a membrane-bound ligand expressed by bone marrow stromal cells. Because soluble recombinant TRANCE is a suboptimal osteoclastogenic stimulus, and to eliminate the need for such dependence on stromal cells, membrane-bound TRANCE was expressed in hematopoietic precursors using retroviral gene transfer. Four TRANCE-expressing osteoclast cell lines were established that continuously generate large numbers of multinucleated cells and express tartrate-resistant acid phosphatase and calcitonin receptors. The multinuclear cells are long-lived and either fuse continuously with each other and with mononuclear cells to form enormous syncytia, or separate to form daughter multinuclear cells. When formed on bone, but not on plastic, the majority of multinuclear cells develop actin rings on bone, and resorb bone, suggesting that bone matrix may provide additional signals that facilitate osteoclastic functional maturation. Surprisingly, multinuclear cells originate from fusion of proliferating mononuclear cells that strongly express the mature macrophage markers F4/80 and Fc receptor, which are not expressed by osteoclasts. These results indicate that osteoclasts can be derived from F4/80-positive and Fc receptor-positive cells, and that TRANCE induces osteoclastic differentiation partly by suppressing the macrophage phenotype.

Animals↗

Up-regulation of urokinase-type plasminogen activator and its receptor correlates with enhanced invasion activity of human glioma cells mediated by transforming growth factor-alpha or basic fibroblast growth factor.

Glioblastoma multiforme is a highly malignant tumor that is extremely refractory to therapy. One reason is its highly invasive nature into brain tissue. Metalloproteinases and their inhibitors, plasminogen activators (PA) and their inhibitors and cathepsins are thought to be involved in invasion by tumor cells. In this study, we determined if the urokinase-type plasminogen activator (uPA) and/or the urokinase-type plasminogen activator receptor (uPAR) were responsible for the invasion activity of a human glioma cell line. We determined the invasion activity of a human glioma U251 cell line using an in vitro invasion assay system. A 2.4- to 5.8-fold increase in invasion activity was observed in the presence of basic fibroblast growth factor (bFGF) or transforming growth factor (TGF)-alpha. Northern blot analysis showed that bFCF and TGF-alpha treatment was associated with increases in cellular mRNA levels of uPA and uPAR. Zymographic activity correlated to mRNA levels of uPA and uPAR. Addition of an anti-uPAR monoclonal antibody significantly inhibited the invasion activity induced by bFGF- and TGF-alpha. Irsogladine, an inhibitor of uPA synthesis, also blocked the invasion activity. These observations suggest that uPA and its receptor have a role in the invasion process of human gliomas.

Fibroblast Growth Factor 2↗

Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation.

Osteoclasts are bone-resorbing cells derived from haematopoietic precursors of the monocyte-macrophage lineage. Mice lacking Fos (encoding c-Fos) develop osteopetrosis due to an early differentiation block in the osteoclast lineage. c-Fos is a component of the dimeric transcription factor activator protein-1 (Ap-1), which is composed mainly of Fos (c-Fos, FosB, Fra-1 and Fra-2) and Jun proteins (c-Jun, JunB and JunD). Unlike Fra-1 (encoded by Fosl1), c-Fos contains transactivation domains required for oncogenesis and cellular transformation. The mechanism by which c-Fos exerts its specific function in osteoclast differentiation is not understood. Here we show by retroviral-gene transfer that all four Fos proteins, but not the Jun proteins, rescue the differentiation block in vitro. Structure-function analysis demonstrated that the major carboxy-terminal transactivation domains of c-Fos and FosB are dispensable and that Fra-1 (which lacks transactivation domains) has the highest rescue activity. Moreover, a transgene expressing Fra-1 rescues the osteopetrosis of c-Fos-mutant mice in vivo. The osteoclast differentiation factor Rankl (also known as TRANCE, ODF and OPGL; refs 8-11) induces transcription of Fosl1 in a c-Fos-dependent manner, thereby establishing a link between Rank signalling and the expression of Ap-1 proteins in osteoclast differentiation.

Animals↗

Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1.

Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-autonomous increase in the number of mature osteoblasts. Moreover, osteoblast differentiation, but not proliferation, was enhanced and osteoclastogenesis was also elevated in vitro. These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions.

Animals↗

Hospital capacity and post-transplant survival after allogeneic bone marrow transplantation: analysis of data from the Japan Society for Hematopoietic Cell Transplantation.

The association between hospital capacity and survival after allogeneic bone marrow transplantation (allo-BMT) was examined using the dataset accumulated by the Japan Society of Hematopoietic Cell Transplantations (JSHCT). The subjects were 3134 patients who received first allo-BMTs between 1991 and 1997 reported to the JSHCT. They were divided into three groups by cumulative hospital experience of allo-BMTs: low volume (capacity) (LV; < or = 25 cases), moderate volume (capacity) (MV; 26-75 cases) and high volume (capacity) (HV; > or = 76 cases). Using a proportional hazards model, the association of hospital experience with early survival at day 100 (D100S), and overall survival (OS) were examined. For leukemia patients, leukemia-free survival (LFS) was also analyzed. When HV was defined as the reference group, the hazard ratios (HRs) of OS for all subjects were 1.10 (95% confidence interval; 0.97-1.25) for MV and 1.25 for LV (1.08-1.44). The HRs with D100S were 1.20 (0.96-1.51) for MV and 1.40 (1.08-1.80) for LV. Larger values were observed for OS and D100S in cases of leukemia. Survival after BMT from sibling donors was clearly influenced by hospital experience, but this was not the case from unrelated donors. These findings suggest that size of the transplant team should be considered in order to improve the outcome of sibling BMT in general.

Adolescent↗