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Biomedical subjects

T Shimizu

Publications and source records attributed to T Shimizu.

At least 127 records · Page 7Linked to original sources
PubMed2003

Genetic mapping of the absence of third molars in EL mice to chromosome 3.

We noted the absence of all 4 third molars (M3) in Epilepsy-Like disorder (EL) mice, an animal model for the study of epilepsy. This study was conducted to identify the major candidate chromosome and to detect the region that included the candidate gene causing the absence of M3 in EL mice. Linkage analysis was performed on genetic crosses of EL mice and MSM (Mus musculus molossinus) strain mice, which had a normal complement of teeth. Genome-wide screening by individual genotyping of F(2) intercross mice identified mouse chromosome 3 as one of the candidate chromosomes. Based on high linkage scores in detailed genotyping of F(2) intercross and N(2) backcross mice, the candidate locus for the absence of M3 in EL mice was mapped on the middle of chromosome 3.

Animals↗
PubMed2003

Increased vascular endothelial growth factor in acute eosinophilic pneumonia.

Acute eosinophilic pneumonia (AEP) is associated with the presence of diffuse pulmonary infiltrates on the chest radiograph and an increased number of eosinophils and an elevation of interleukin (IL)-5 levels in bronchoalveolar lavage (BAL) fluid. Vascular endothelial growth factor (VEGF) is a constitutively expressed protein encoded by messenger ribonucleic acid in human eosinophils and is released following stimulation with IL-5. However, the roles of IL-5 and VEGF in the pathogenesis or activity of this disease have not been clarified. The authors investigated the cells and the levels of these two factors in BAL fluid in five AEP patients and five normal controls before and after corticosteroid treatment. The absolute number of eosinophils-mL(-1), IL-5 and VEGF levels in patients before treatment were higher than in controls (53.8 versus 0.3 x 10(4) x mL(-1), 490.1 versus 5.2 pg x mL(-1) and 643.0 versus 133.9 pg x mL(-1), respectively). IL-5 and VEGF rapidly decreased to the control level in parallel with clinical improvement. The relationship between eosinophilia and IL-5 and VEGF levels was strongly significant. Elevated interleukin-5 in the lung may initiate the recruitment of eosinophils and enhance the release of mediators, such as vascular endothelial growth factor from eosinophils, which, in turn, increases the permeability of blood vessels.

Acute Disease↗
PubMed2003

Engineered IGF-I expression induces glandular enlargement in the murine prostate.

IGF-I has been implicated as a factor that may predispose one to prostate cancer and to benign prostatic hypertrophy (BPH). We established murine IGF-I transgenic mice under the control of rat probasin promoter and analysed the histology of the murine IGF-I-overexpressing prostate. Immunohistochemically, IGF-I was expressed in prostatic epithelial cells or basement membranes of the ventral, dorsal and lateral lobes in a line of IGF-I transgenic mice, but not in their control littermates. The anterior lobe did not express IGF-I. IGF-binding protein-3 (IGFBP-3), inhibitory to the mitogenic action of IGF-I, was detected in epithelial cells of prostatic ventral lobes, but not in those of the dorsal, lateral or anterior lobes of IGF-I transgenic mice. In controls, IGFBP-3 was not detected in epithelial cells of any prostatic lobe. Macroscopic prostatic size and the appearance of IGF-I transgenic mice were comparable with those of their control littermates of the same age. With a computed morphometric analysis, epithelial glands and intraglandular lumens in the prostatic lobes except the ventral lobe were smaller at 17 Months of age than at 14 Months both in IGF-I transgenic mice and controls. Glands and intraglandular lumens in the ventral prostatic lobes of IGF-I transgenic mice expressing more IGF-I protein in the prostate than controls were dense and enlarged similar to cysts compared with those of non-transgenic littermates without showing epithelial growth. Glands and lumens in the dorsal and lateral lobes of the IGF-I transgenic mice were also larger than controls at 14 and/or 17 Months of age. Glands in the anterior prostatic lobe of the IGF-I transgenic mice were not morphologically or morphometrically different from those of non-transgenic littermates. In conclusion, IGF-I transgenic mice under the control of rat probasin promoter showed more dense and enlarged epithelial glands in their prostatic ventral, dorsal and lateral lobes.

Aging↗
PubMed2003

Disseminated Mycobacterium avium complex (DMAC) in an immunocompetent adult.

A female patient with multiple osteomyelitis and pulmonary Mycobacterium avium disease visited an orthopaedic clinic with back pain. Systemic bone scan showed multiple sites of increased radioactivity in the vertebral bodies, right scapula, femurs and ribs. M. avium was isolated from sputum and a sample aspirated from the right scapula. The route of infection was unknown as there was no history of trauma or surgery. HIV testing was negative. As there was no underlying immunological disease she was diagnosed as disseminated M. avium complex (DMAC) disease in an immunocompetent adult. Cytokine production on several stimuli from peripheral blood mononuclear cells was similar to that in pulmonary M. avium patients. Sequence analysis of IFN-gamma receptor revealed no nucleotide substitution. We detected serotypes 1, 2 and 4 from mycobacteria cultured from the right scapula, and conclude that this case could be the result of undetected immune deficiency and/or unrecognised virulence of the infecting isolate.

Female↗
PubMed2003

Impaired interleukin-1beta converting enzyme (ICE) activity in patients with pulmonary tuberculosis.

We measured the activity of IL-1beta converting enzyme (ICE) of monocytes from pulmonary tuberculosis (PTB) patients. Peripheral blood mononuclear cells (PBMCs) and serum were collected from PTB patients (n = 16) and healthy subjects (n = 6). Serum IL-18 levels were significantly higher in PTB patients (515.9 +/- 326.5 pg/ml) than in controls (108.7 +/- 65.2 pg/ml) (P < 0.01), but gradually decreased with tuberculosis therapy. ICE activity was significantly lower in TB patients (65.3 +/- 34.4 vs. 142.2 +/- 75.6 U/mg) (P < 0.05). Serum IL-18 levels inversely correlated with ICE activity (P < 0.05). Altered ICE activity may explain why there is reduced IFN-gamma production from PBMCs; however, serum IL-18 is probably not regulated by ICE in monocytes in TB patients.

Caspase 1↗
PubMed2003

Combined minimally invasive procedure for descending thoracic aortic aneurysm with left main coronary artery disease.

A 78-year-old man had a descending thoracic aortic aneurysm with left main coronary artery disease. Combined beating heart coronary artery bypass and endovascular thoracic aortic aneurysm repair was performed without cardiopulmonary bypass. The left anterior descending artery and the obtuse marginal branch of the left circumflex artery were revascularized through a left antero-lateral small thoracotomy. The aneurysm was excluded with stent grafts through a small femoral incision. This combined less invasive procedure is a promising approach providing better surgical results in patients with thoracic aortic aneurysm and severe coronary artery disease.

Aged↗
PubMed2002

A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine.

A variable number of tandem repeats (VNTR) in the second intron of the serotonin transporter gene (STin2) has been studied in association with the susceptibility to affective disorders. Recently, it was reported that selective serotonin reuptake inhibitors were more effective in patients with major depressive disorder having the homozygous allele pair (12-copy/12-copy) of VNTR in the STin2 than in ones having other allele combinations. As the study had methodological problems, further studies are needed to confirm the above finding. Therefore, the authors investigated whether the allelic variation of VNTR in the STin2 was associated with the antidepressant response to fluvoxamine in 66 patients with major depressive disorder. Fluvoxamine was prescribed up to 200 mg/day in the dosing protocol for 6 weeks. The present study showed no significant association between the polymorphism of VNTR in the STin2 and the treatment response to fluvoxamine.

Adult↗
PubMed2002

Implanted octacalcium phosphate is more resorbable than beta-tricalcium phosphate and hydroxyapatite.

Our previous studies have suggested that synthetic octacalcium phosphate (OCP) could be resorbed and replaced by newly formed bone if implanted in rat skull defects. We hypothesized that the implanted OCP is more resorbable than other commonly used bone graft substitutes of calcium phosphate compounds, such as hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP). To test the hypothesis, the present study was designed to compare histomorphometrically resorption of the implanted OCP, HA, and beta-TCP, which were kept in the experimental cranial defect of rats for a long term. A full thickness of standardized trephine defect was made in the rat parietal bone, and the same volume of granules of OCP, HA, and beta-TCP were implanted into the defect. Five specimens of each group were fixed 6 months after implantation. The percentage of remaining implants (r-Imp%) and newly formed bone (n-Bone%) in the defect was analyzed histomorphometrically. The statistical analysis showed that the r-Imp% of OCP was significantly lower than that of HA and beta-TCP. In contrast, the n-Bone% of OCP was significantly higher than that of HA and beta-TCP. The present study has shown that the implanted OCP in the rat cranial defect is more resorbable than the implanted beta-TCP and HA, whereas the implanted OCP enhances bone formation more than the implanted beta-TCP and HA.

Animals↗
PubMed2002

Vitamin E ointment at high dose levels suppresses contact dermatitis in rats by stabilizing keratinocytes.

OBJECTIVE: The pharmacological effect of vitamin E ointment at high dose levels was investigated in rats and mice during the development of contact dermatitis. MATERIALS AND METHODS: Allergic or irritant contact dermatitis was induced in sensitized or unsensitized animals by topical application of chemical agent(s). Cultured keratinocytes were prepared from dorsal skin of rats. RESULTS: The vitamin E ointment at 20-40% suppressed allergic and irritant contact dermatitis, exerting a comparable effect to that of 0.5% prednisolone ointment. Microscopic findings revealed that 20% vitamin E ointment reduced the keratinocyte damage, whereas 0.5% prednisolone was ineffective. The protective action of vitamin E on keratinocyte damage was also confirmed in a cell culture experiment. Furthermore, 20% vitamin E ointment blocked down-regulation of skin barrier function induced by contact dermatitis, although 0.5% prednisolone ointment was inactive. CONCLUSIONS: These results indicate that 20% vitamin E ointment suppresses contact dermatitis by stabilizing keratinocytes, concomitantly with novel, interesting properties.

Administration, Topical↗
PubMed2002

Contractile responses to reactive oxygen species in the canine basilar artery in vitro: selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger.

BACKGROUND: Cerebral vasospasm is one of the important pathological phenomena which influence morbidity and mortality following subarachnoid haemorrhage. Reactive oxygen species (ROSs) generated by the autoxidation of oxyhemoglobin to methemoglobin may be one of the essential factors in the pathogenesis of cerebral vasospasm. The direct vasocontractile effects of hydrogen peroxide (H(2)O(2)), superoxide anion (O(2)(-)), and hydroxyl radical (*OH) on the canine basilar artery and the inhibitory effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a new *OH scavenger, were investigated. METHOD: Isometric tension was recorded in basilar artery rings from dogs in vitro. H(2)O(2), pyrogallol (O(2)(-) donor), and vitamin C (VitC)/Fe(2+) (*OH-generating system) were used to generate the ROSs. FINDINGS: H(2)O(2) (10 micromol/L), pyrogallol (10 micromol/L), and VitC/Fe(2+) (100 micromol/L each) induced fast onset and transient, slow onset and transient, and sustained contraction, respectively, in the canine basilar artery. Contractions induced by H(2)O(2) were almost completely inhibited by pre-incubation with catalase (800 U/mL) and those by pyrogallol with superoxide dismutase (150 U/mL), but neither with MCI-186 (10 micromol/L). The contraction induced by VitC/Fe(2+) was clearly inhibited by pre-incubation with MCI-186, but not with catalase or superoxide dismutase. INTERPRETATION: ROSs have direct vasocontractile effects on the canine basilar artery in vitro, but different ROSs have different contractile characteristics. Such contractions might be related to the pathophysiology of cerebral vasospasm. MCI-186 had a clear and selective inhibitory effect against *OH-induced contraction in vitro. Comparison of different radical scavengers may be important in pharmacological assessment, especially targeted on cerebral vasospasm.

Animals↗
PubMed2002

Selective production of organic acids in anaerobic acid reactor by pH control.

The selective production of organic acids by anaerobic acidogenesis with pH control was examined using a chemostat culture. The results showed that the product spectrum in the acid reactor strongly depended on the culture pH. Under acidic and neutral conditions, the main products were butyric acid, while acetic and propionic acids were the main products under the basic condition. This phenomenon was reversible between the acidic and basic conditions, and was not affected by the dilution rate. The change in the main products was caused by the change in the dominant microbial populations, from butyric acid-producing bacteria to propionic acid-producing bacteria in the acid reactor due to the pH shift. The control of culture pH was considered to be a useful way for controlling the product spectrum in the anaerobic acid reactor.

Acetic Acid↗
PubMed2002

Clinical and neuroradiological improvement in chronic acquired hepatocerebral degeneration after branched-chain amino acid therapy.

We report two patients with chronic acquired hepatocerebral degeneration (CAHD) who showed neurological and radiological improvement after the administration of branched-chain amino acids (BAA). The first patient with chronic hepatitis C presented with progressive parkinsonism for 7 months, whereas the second patient with liver cirrhosis presented with progressive ataxia for 15 months. T1-weighted magnetic resonance imaging (MRI) showed symmetric high intensity signals in the lenticular nuclei in both patients. In the first patient, single photon emission computed tomography (SPECT) disclosed a marked decrease in cerebral blood flow in the parieto-occipital regions. In the second patient, T2-weighted MRI demonstrated symmetric high intensity signals in the deep cerebral and cerebellar white matter. After the administration of BAA, their neurological signs and radiological abnormalities markedly improved in both patients. CAHD might be a reversible and treatable disorder where aromatic amino acids are deeply involved in its pathogenesis.

Aged↗
PubMed2002

Role of the platelet-activating factor (PAF) receptor during pulmonary infection with gram negative bacteria.

The lipid mediator PAF plays an important role in the phagocytosis of particles, including bacteria, and consequent production of pro-inflammatory cytokines, such as TNF-alpha and IL-8. Using a PAF receptor antagonist (UK-74,505) and PAF receptor knock-out mice, we have investigated the relevance of PAF for the inflammatory changes and lethality after pulmonary infection with the gram-negative bacteria Klebsiella pneumoniae in mice. At an inoculum of 3 x 10(6) bacteria, there was marked pulmonary (bronchoalveolar lavage and lung) neutrophilia that started early (2.5 h after infection) and peaked at 48 h. All animals were dead by day 4 of infection. The chemokine KC and the pro-inflammatory cytokine TNF-alpha increased rapidly and persisted for 48 h in the lungs. Pretreatment with UK-74,505 (30 mg kg(-1) per day, p.o.) had no significant effects on the number of infiltrating neutrophils in BAL fluid or lung tissue, as assessed by histology and measuring myeloperoxidase, or on the concentrations of KC. In contrast, concentrations of TNF-alpha and the number of bacteria inside neutrophils were significantly diminished. In order to support a role for the PAF during K. pneumoniae infection, experiments were also carried out in PAFR-deficient mice. In the latter animals, lethality occurred earlier than in wild-type controls. This was associated with greater number of bacteria in lung tissue and diminished percentage of neutrophils containing bacteria in their cytoplasm. Our results suggest that PAF, acting on its receptor, plays a protective role during infection with K. pneumoniae in mice.

Animals↗
PubMed2002

Diagnosis of Werner syndrome by immunoblot analysis.

Werner syndrome (WS) is caused by mutations in the gene encoding RecQ type DNA helicase (WRN). We report a 53-year-old Japanese male with WS who initially presented with skin ulcers on the feet and the left elbow. The patient had a high-pitched voice, hoarseness, a characteristic bird-like facial appearance with a beak-shaped nose, canities and juvenile cataracts. Immunoblot analysis using a monoclonal antibody directed against the WS gene product DNA helicase revealed that the patient's leucocytes lacked this particular molecule, confirming the diagnosis of WS. This new immunoblot system therefore enables the diagnosis of WS to be made without the need to undertake more complex mutational analysis.

DNA Helicases↗
PubMed2002

Profiles of cell-to-cell interaction of Mycobacterium intracellulare-induced immunosuppressive macrophages with target T cells in terms of suppressor signal transmission.

Previously, we have found that immunosuppressive macrophages (M(phi)s) induced by Mycobacterium intracellulare-infection (MI-M(phi)s) required cell contact with target T cells to express their suppressor activity against concanavalin A (Con A)-induced T cell mitogenesis. In this study, we examined the profiles of cell-to-cell interaction of MI-M(phi)s with target T cells. First, MI-M(phi)s displayed suppressor activity in an H-2 allele-unrestricted manner, indicating that MHC molecules are not required for cell contact. The suppressor activity of MI-M(phi)s was reduced markedly by paraformaldehyde fixation or treatment with cytochalasin B or colchicine, indicating that vital membrane functions are required for their suppressor activity. Secondly, the suppressor activity of MI-M(phi)s was independent of cell-to-cell interaction via CD40 ligand/CD40 and M(phi)-derived indoleamine 2,3-dioxygenase, which causes rapid degradation of tryptophan in T cells. Thirdly, precultivation of splenocytes with MI-M(phi)s, allowing cell-to-cell contact, reduced Con A- or anti-CD3 antibody-induced mitogenesis but not phorbol myristate acetate/calcium ionophore A23187-elicited proliferation of T cells. In addition, co-cultivation of T cells with MI-M(phi)s caused marked changes in profiles of the tyrosine phosphorylation of 33 kDa, 34 kDa and 35-kDa proteins and, moreover, the activation of protein kinase C and its translocation to the cell membrane. It thus appears that suppressor signals of MI-M(phi)s, which are transmitted to the target T cells via cell contact, principally cross-talk with the early signalling events before the activation of PKC and/or intracellular calcium mobilization.

Animals↗
PubMed2002

Oligonucleotide probe for detecting Enterobacteriaceae by in situ hybridization.

AIMS: To develop oligonucleotide probes for visualizing bacteria belonging to Enterobacteriaceae. METHODS AND RESULTS: 24-mer oligonucleotide probe (probe D) was designed by comparison of 16S rDNA sequences of 35 species of Enterobacteriaceae, eight species of Vibrionaceae and six species of Pasteurellaceae. The sequence of the probe corresponding to the complementary sequence of a position 1251-1274 of Escherichia coli 16S rRNA was found to be a highly conserved region of 16S rDNA sequence in Enterobacteriaceae different from that of Vibrionaceae and Pasteurellaceae. The fluorescent dye-labelled probe was tested for the specificity by in situ hybridization and epifluorescence microscopy. Seventy-six out of 78 strains belonging to Enterobacteriaceae were visualized in an optimal hybridization condition. No bacterial strains belonging to Vibrionaceae (31 strains) and Gram-positive bacteria (three strains) were visualized. CONCLUSIONS: In situ hybridization using probe D allows the detection of bacterial cells belonging to Enterobacteriaceae without false positive reaction. SIGNIFICANCE AND IMPACT OF THE STUDY: In situ hybridization techniques using the probe D are potential tools for detecting Enterobacteriaceae in food and water samples.

DNA, Bacterial↗