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Biomedical subjects

M Takiguchi

Publications and source records attributed to M Takiguchi.

At least 37 records · Page 2Linked to original sources

Mice lacking CCAAt/enhancer-binding protein-alpha show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs.

The lung-specific surfactant proteins (SP) are essential for normal respiratory function. Transcription factors may play an important role in the regulation of surfactant proteins. The CCAAT/enhancer-binding protein (C/EBP) family consists of transcription factors that can stimulate expression of genes in lipid-metabolizing epithelial cells. C/EBPalpha-deficient mice have been shown to exhibit abnormal pulmonary histopathology. Recently, we demonstrated that C/EBP family members are differentially expressed in alveolar type II cell proliferation and in pulmonary fibrosis. In the present study, to investigate whether the C/EBP family would be involved in the regulation of surfactant proteins, we examined the protein expression of SP-A, and SP-C, and mRNA expression of SP-A, SP-B, and SP-C in the lungs from newborn C/EBPalpha-deficient mice. Using immunohistochemistry, we demonstrated that positive cells for SP-C, specific to alveolar type II cells, in the lungs were more abundant in the newborn C/EBPalpha-deficient mice than in control mice, which suggests the hyperproliferation of alveolar type II cells in the lungs of the C/EBPalpha-deficient mice. In situ hybridization analysis revealed that expression of SP-A, SP-B, and SP-C mRNAs were increased in the lungs of newborn C/EBPalpha-deficient mice. Northern blot analysis revealed that surfactant protein mRNAs were also increased. Thus, these results suggest that C/EBPalpha may play a key role in the proliferation of alveolar type II cells and the regulation of genes of surfactant protein.

Animals↗

Visual demonstration of hepatitis C virus-specific memory CD8(+) T-cell expansion in patients with acute hepatitis C.

Hepatitis C virus (HCV)-specific CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HCV were quantitatively analyzed by flow cytometry using an HLA-B*3501-HCV epitope tetrameric complex. In chronic hepatitis C, tetramer(+)CD8(+) T cells were detected at frequencies ranging from 0.05% to 0.12% of total CD8(+) T cells. The number of tetramer(+)CD8(+) T cells in acute phase PBMCs from patients with acute hepatitis C was about 3 to 5 times higher than in recovery phase PBMCs from the same patients and in PBMCs from patients with chronic hepatitis C. Expanding tetramer(+)CD8(+) T cells in PBMCs from patients with acute hepatitis C express a CD28(+)CD45RA(-) memory T-cell phenotype. In contrast, tetramer(+)CD8(+) T cells in PBMCs from patients with chronic hepatitis C did not predominantly express this phenotype. These tetramer(+)CD8(+) T cells did not have perforin in their cytoplasma. The present study visually showed that a high number of circulating HCV-specific CD8(+) T cells in acute phase PBMCs from patients with acute hepatitis C are mostly memory T cells.

Acute Disease↗

Malignant seminoma with systemic metastases in a dog.

A three-year-old male crossbred dog was presented with multiple cutaneous nodules on the dorsum. Unilateral testicular enlargement ensued. Histopathological examination of testicular tissue and the skin lesions revealed a malignant seminoma. Despite the initiation of adjuvant chemotherapy, the dog died three months later due to systemic metastases of the seminoma to the skin, scrotum, eyes, liver, kidney and peritoneum.

Animals↗

Radicular cyst associated with a primary molar following pulp therapy: a case report.

A radicular cyst arising from the primary second molar and causing displacement of the permanent successor to the lower border of the mandible, with accompanying buccal expansion, was examined clinically and radiographically. Extraction of the primary molar and extirpation of the cyst led to uneventful healing. The primary molar had received pulp treatment with therapeutic agents approximately 1.5 years prior to the patient's first visit. The relationship between pulp treatment and rapid growth of the radicular cyst is discussed.

Anti-Infective Agents, Local↗

A serological survey of minute virus of canines (MVC; canine parvovirus type-1) in dogs in the Tokai area of Japan.

A serological survey for antibodies to minute virus of canines (MVC) by use of a hemagglutination-inhibition (HI) test was performed on sera collected from dogs in the Tokai area of Japan. Forty-one of 266 (15.4%) sera had positive titers of 1:40 or higher against the MVC. Results suggest that MVC may have been present in dogs in Japan since, at least, 1990. From this serosurvey, MVC appears to be established in the dog population in Japan. MVC may have a role as a newly recognized viral pathogen of dogs in Japan.

Animals↗

Modification of guide wire for 22-gauge safe guide.

Safe guide is a central venous catheterization kit that serves as both pilot needle and introducer. With a single puncture, a guide wire can be introduced by inserting it through the side port of the 22-gauge needle. The advantage is that this needle can be placed within a blood vessel using no more force than is required to insert a pilot needle. However, the 0.018-inch guide wire is vulnerable to kinks and locking. Because the tip has been shaped into a sharp J-shaped angle, it can kink at the puncture site, and locking sometimes occurs when the guide wire is passed through the side port of the needle, or when the dilator is introduced. In order to resolve these issues, we modified the device by making an experimental guide wire with a gentler angle. In addition, we fortified the body of the wire without altering its thickness. We then investigated the effectiveness of our modifications. The subjects of the study were 120 patients, who required central venous catheterization. They were divided into 2 groups. The original J-type guide wire was used in one group (Group A: n = 60) and the modified guide wire in the other group (Group B: n = 60). Catheters were introduced by right internal jugular vein puncture. We observed the following: 1) incidence of back-flow appearing at withdrawal of the needle without back-flow during advancement, 2) incidence of kinking or locking of the guide wire when it was passed through the side port, 3) incidence of kinking of the guide wire at the puncture site when introducing the dilator, and 4) complications. The results were as follows: 1) back-flow appeared upon withdrawal in 3.4% of both groups; 2) kinking and locking occurred when passing the guide wire through the side port of the Safe guide needle in 16.7% of Group A and 1.7% of Group B; 3) kinking of the guide wire occurred when introducing the dilator in 5 % of Group A in contrast to 0% in Group B; 4) the only complication caused by the passing of the guide wire was accidental puncture of the common carotid artery, which occurred in 1.7% of both groups. No problems with the guide wire were noted in either group. The use of our modified guide wire decreased the incidence of kinking and locking of the guide wire when passing it through the side port. In addition, no guide wire kinking at the puncture site occurred when introducing the dilator. Issues associated with the original J-type guide wire were resolved by 1) changing the guide wire tip to a gentler angle, and 2) fortifying the guide wire by altering its composition.

Catheterization, Central Venous↗

Influence of body fat on the onset of vecuronium induced neuromuscular blockade.

The onset time of vecuronium, a muscle relaxant, was measured after a bolus intravenous injection of 0.15 mg kg(-1) of vecuronium into 40 surgical patients aged 59-64 years. The onset time was then compared between male and female patients and the relationship between onset time and body fat (% of body weight) was analyzed. Arterial plasma concentrations of vecuronium were measured at 75, 195, and 375 sec after administration of vecuronium to 8 patients. The female patients (n = 23) showed a shorter onset time and more body fat than the male patients (n = 17). The onset time significantly decreased with increasing body fat in both groups. When only females with body fat of less than 30% (n = 10) were compared with the male group (all male patients had body fat of less than 30%), the body fat, onset time, and regression lines between the onset time and the body fat did not differ significantly. Except in the patient with the highest body fat, plasma concentrations at 195 and 375 sec significantly increased with increasing body fat. We concluded that the higher body fat in females is largely responsible for the faster onset of vecuronium action in females. A smaller distribution volume of vecuronium may also be one of the reasons for the faster onset of vecuronium in females.

Adipose Tissue↗

Valsalva maneuver prevents guide wire trouble associated with 22-gauge safe guide.

UNLABELLED: The Safe guide is a central venous puncture needle that serves as both a pilot needle and as an introducer. A guide wire can be inserted into a vein through the side port at the hub of the 22-gauge Safe guides needle initially inserted as a pilot needle. However, guide wire insertion may fail due to kinking or locking at the side port. Increasing airway pressure to 20 cm H2O by squeezing a respiratory bag during insertion of the guide wire together with venous puncture was attempted to determine if would decrease guide wire trouble. SUBJECTS AND METHODS: A total of 120 patients scheduled for central venous catheterization by right internal jugular puncture were divided into two groups. Patients in group-A (n = 60) were catheterized by the conventional method and those in group-B (n = 60) were catheterized by applying the Valsalva maneuver. Three observations were made: 1) Frequency of cases in which blood back-flow occurred during withdrawal only and not upon advancement of the puncture needle. 2) Frequency of cases in which kinking and/or locking of the guide wire occurred at the hub during its insertion. And 3) the occurrence of complications. RESULTS: 1) The patency of the vein was preserved and blood back-flow was obtained during advancement of the puncture needle in all cases in which the Valsalva maneuver was applied. 2) The incidence of kinking and/or locking during insertion of the guide wire decreased from 16.7% to 3.4% by applying positive airway pressure during the Valsalva maneuver. And 3) complications were negligible. Additionally, the application of the Valsalva maneuver allowed successful guide wire insertion in 6 out of 9 cases (67%) in group-A, in which the initial attempt using the conventional method had failed. CONCLUSION: The application of positive airway pressure using the Valsalva maneuver may prevent the guide wire trouble associated with the 22-gauge Safe guide.

Catheterization, Central Venous↗

Nonstandard peptide binding revealed by crystal structures of HLA-B*5101 complexed with HIV immunodominant epitopes.

The crystal structures of the human MHC class I allele HLA-B*5101 in complex with 8-mer, TAFTIPSI, and 9-mer, LPPVVAKEI, immunodominant peptide epitopes from HIV-1 have been determined by x-ray crystallography. In both complexes, the hydrogen-bonding network in the N-terminal anchor (P1) pocket is rearranged as a result of the replacement of the standard tyrosine with histidine at position 171. This results in a nonstandard positioning of the peptide N terminus, which is recognized by B*5101-restricted T cell clones. Unexpectedly, the P5 peptide residues appear to act as anchors, drawing the peptides unusually deeply into the peptide-binding groove of B51. The unique characteristics of P1 and P5 are likely to be responsible for the zig-zag conformation of the 9-mer peptide and the slow assembly of B*5101. A comparison of the surface characteristics in the alpha1-helix C-terminal region for B51 and other MHC class I alleles highlights mainly electrostatic differences that may be important in determining the specificity of human killer cell Ig-like receptor binding.

Amino Acid Motifs↗

The gene for hepatocyte nuclear factor (HNF)-4alpha is activated by glucocorticoids and glucagon, and repressed by insulin in rat liver.

The gene for a transcription factor hepatocyte nuclear factor-4alpha (HNF-4alpha) is responsible for maturity-onset diabetes of the young, type 1. We examined hormonal regulation of the HNF-4alpha gene in the liver. Stimulation of primary-cultured rat hepatocytes with dexamethasone or glucagon led to induction of HNF-4alpha mRNA, being antagonized by insulin. In the liver of streptozotocin-induced diabetic rat, mRNA and protein levels for HNF-4alpha were elevated, and were normalized by insulin treatment. Therefore, HNF-4alpha in the liver is likely to be involved in the regulation of glucose metabolism in response to these hormones.

Animals↗

Induction of endothelial nitric-oxide synthase in rat brain astrocytes by systemic lipopolysaccharide treatment.

In the brain, three isoforms of nitric oxide (NO) synthase (NOS), namely neuronal NOS (nNOS, NOS1), inducible NOS (iNOS, NOS2), and endothelial NOS (eNOS, NOS3), have been implicated in biological roles such as neurotransmission, neurotoxicity, immune function, and blood vessel regulation, each isoform exhibiting in part overlapping roles. Previous studies showed that iNOS is induced in the brain by systemic treatment with lipopolysaccharide (LPS), a Gram-negative bacteria-derived stimulant of the innate immune system. Here we found that eNOS mRNA is induced in the rat brain by intraperitoneal injection of LPS of a smaller amount than that required for induction of iNOS mRNA. The induction of eNOS mRNA was followed by an increase in eNOS protein. Immunohistochemical analysis revealed that eNOS is located in astrocytes of both gray and white matters as well as in blood vessels. Induction of eNOS in response to a low dose of LPS, together with its localization in major components of the blood-brain barrier, suggests that brain eNOS is involved in early pathophysiologic response against systemic infection before iNOS is induced with progression of the infection.

Animals↗

Suppressive effects of dominant negative ras mutant N116Y on transformed phenotypes of human bladder cancer cells.

To investigate the suppressive effect of dominant negative H-ras mutant N116Y on transformed phenotypes, we established two N116Y ras mutant stable transfectant clones (C5, C13) of human bladder cancer cell line, UMUC-2. These N116Y ras mutant transfectants, especially the C5 cells, showed a dramatic change of cellular morphology and significantly reduced growth in soft agar compared to their control. Furthermore, phosphorylation of the Jun NH2-terminal kinase (JNK) was significantly decreased in these transfectants compared to the control. These results suggest that the N116Y-induced suppression of transformed phenotypes in UMUC-2 cells is associated with inhibition of JNK phosphorylation.

Cell Transformation, Neoplastic↗

A single CTL clone can recognize a naturally processed HIV-1 epitope presented by two different HLA class I molecules.

Although it is known that a single peptide can be recognized by CTL restricted to two MHC class I alleles, there is no direct evidence for presentation of a single peptide by two MHC class I molecules. Furthermore, it is unclear whether such peptides are presented to the same T cell or to different T cells. Our previous study suggested that CTL recognition of the human immunodeficiency virus-1 (HIV-1) Pol HIV-B35-SF2-24 epitope (IPLTEEAEL) occurs via both HLA-B35 and HLA-B51 restriction. Here we provide the first direct evidence that a single CTL clone can recognize this peptide presented by both HLA-B35 and HLA-B51. Furthermore, we directly purified this peptide eluted from both HLA-B*3501 and HLA-B*5101 molecules isolated from target cells infected with HIV-1 recombinant vaccinia virus. These results demonstrate that HIV-B35-SF2-24 is a naturally processed peptide which is presented by both HLA-B*3501 and HLA-B*5101. TCR analysis of one CTL clone suggested that it is a single clone. B*3501-SF2-24-tetrameric complexes inhibited both HLA-B*3501- and HLA-B*5101-restricted recognition of this clone, suggesting that the TCR of this clone cross-recognize the structure of both HLA class I-peptide complexes.

Amino Acid Sequence↗

F-wave latency serves as the most reproducible measure in nerve conduction studies of diabetic polyneuropathy: multicentre analysis in healthy subjects and patients with diabetic polyneuropathy.

AIMS/HYPOTHESIS: For use in future drug development for diabetic polyneuropathy, we conducted multicentre trials to assess the reproducibility of nerve conduction studies. METHODS: All measurements were repeated twice at a time interval of 1-4 weeks in 132 healthy subjects (63 men) and 172 patients (99 men) with diabetic polyneuropathy. Using a standardised method, 32 centres participated in the study of control subjects and 65, in patients with diabetic polyneuropathy. Motor nerve conduction studies consisted of stimulating the left median and tibial nerves and recording the compound action potential from abductor policis and adductor hallucis for measuring amplitude, terminal latency and minimal F-wave latency. For sensory conduction studies, sensory nerve action potentials were recorded antidromically from the second digit and the posterior aspect of the lateral malleous after distal stimulation of the left median and sural nerves. We also calculated motor conduction velocity, F-wave conduction velocity and sensory conduction velocity. The relative intertrial variation and intraclass correlation coefficient were used as an index of reproducibility. RESULTS: Of all the measurements, F-wave latency yielded the highest intraclass correlation coefficient with the smallest relative intertrial variation for both median and tibial nerves in both groups. CONCLUSION/INTERPRETATION: Median and tibial F-wave latency provide the most reproducible measures for a nerve conduction study, serving as one of the best measures in multicentre drug trials for diabetic polyneuropathies.

Adult↗

Structure of the infected cell protein 0 gene of canine herpesvirus.

The canine herpesvirus infected cell protein 0 (CICP0) gene was sequenced. The CICP0 gene was transcribed as a 1.4 kb mRNA from the end of the unique long region nearby the internal repeat during early phase of productive infection of the virus. An open reading frame of the gene encodes a polypeptide of 333 amino acids. The RING finger domain and acidic transcriptional activation domain were found at the N-terminus and within the middle region in the deduced amino acid sequence, respectively, suggesting that the CICP0, like the ICP0 of herpes simplex virus 1, is a transactivating protein.

Amino Acid Sequence↗

CTLA4IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice.

MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune syndrome closely resembling systemic lupus erythematosus (SLE) in humans, characterized by hypergammaglobulinemia, various autoantibody production, and the development of fatal glomerulonephritis. We have previously demonstrated that systemic administration of soluble form of CTLA4IgG prevented autoantibody-related diseases in MRL/lpr mice. To test the potential protective effects of CTLA4IgG gene delivery on the development of lupus nephritis, we injected MRL/lpr mice with a recombinant adenovirus vector containing CTLA4IgG gene, Adex1CACTLA4IgG (AdCTLA4IgG). It was demonstrated that a single administration of intravenous injection of AdCTLA4IgG into MRL/lpr mice resulted in almost complete amelioration of lupus nephritis.

Abatacept↗