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Biomedical subjects

Y Yokota

Publications and source records attributed to Y Yokota.

At least 55 records · Page 3Linked to original sources
PubMed2000

Single-tube multiplex PCR for rapid and sensitive diagnosis of subgenus B and other subgenera adenoviruses in clinical samples.

We developed a new diagnostic method of subgenus (Sub) B adenovirus (Ad) in clinical samples using non-nested polymerase chain reaction (PCR). Sequences of the conserved hexon-coding region of representative strains of eight serotypes (3, 7, 11, 14, 16, 21, 34 and 35) of Sub B Ad were heterogeneous. In order to distinguish Ad serotype 3 (Ad 3) and Ad 7 from the other serotypes of Sub B Ad, and to differentiate Ad 3 and 7 from each other, 3 different downstream primers were designed based on the sequence heterogeneity. By a single-tube PCR method using a combination of 6 primers including the 3 new primers, Ads demonstrated to amplify 188, 206, 284, and 301 bp DNA fragments for Ad 3, Ad 7, other Sub B Ads, and non-Sub B Ads, respectively. A total of 114 clinical samples were selected to evaluate the direct applicability of our PCR. The results were compared with previous culture results. Sixty-seven out of 71 (94%) Sub B Ad culture-positive samples, and 15 out of 19 (79%) Sub C or E-positive samples amplified products of the expected size. Two of 20 (10%) culture-negative samples from pharyngoconjunctival fever patients were identified as Ad 3 by the PCR. Four samples, from which non-Ad viruses were isolated, were negative by the PCR. The present study might provide a rapid and sensitive diagnosis method for infections caused by Sub B Ads.

Adenovirus Infections, Human↗
PubMed2000

Uncx4.1 is required for the formation of the pedicles and proximal ribs and acts upstream of Pax9.

The expression of the homeobox gene Uncx4.1 in the somite is restricted to the caudal half of the newly formed somite and sclerotome. Here we show that mice with a targeted mutation of the Uncx4.1 gene exhibit defects in the axial skeleton and ribs. In the absence of Uncx4.1, pedicles of the neural arches and proximal ribs are not formed. In addition, dorsal root ganglia are disorganized. Histological and marker analysis revealed that Uncx4.1 is not necessary for somite segmentation. It is required to maintain the condensation of the caudal half-sclerotome, from which the missing skeletal elements are derived. The loss of proximal ribs in Pax1/Pax9 double mutants and the data presented here argue for a role of Uncx4.1 upstream of Pax9 in the caudolateral sclerotome. Our results further indicate that Uncx4.1 may be involved in the differential cell adhesion properties of the somite.

Animals↗
PubMed2000

Effect of beta-blocker therapy on severe ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy.

Beta-blocker therapy has been shown to improve cardiac function and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). However, whether beta-blockers reduce severe ventricular arrhythmias and sudden cardiac death has not been clarified. The present study was designed to investigate the effects of beta-blockers on non-sustained ventricular tachycardia (VT) and sudden cardiac death in patients with DCM. Sixty-five patients with DCM treated with diuretics, digitalis and angiotensin-converting enzyme inhibitors were assigned to receive beta-blockers (n = 33) or not (n = 32). Mean follow-up was 53+/-30 months. The echocardiographic indices of cardiac function, the incidence of non-sustained VT on Holter monitoring electrocardiograms, and sudden cardiac death rate were compared between the 2 groups. Comparable improvement in cardiac function on echocardiograms was found in the 2 treatment groups. The patient group treated with beta-blockers showed a significant reduction in the prevalence of VT (from 43 to 15%, p<0.05) and the development of new episodes of VT (5 vs. 16%) compared to the group without beta-blockers. The sudden cardiac death rate did not differ between the 2 groups. The results of the present study suggest that beta-blockers are effective in reducing severe ventricular arrhythmias in patients with DCM.

Adrenergic beta-Antagonists↗
PubMed2000

[Surgical treatment for spontaneous hemopneumothorax complicated by delayed re-bleeding: a case report].

A 34-year-old man was admitted to the hospital due to spontaneous hemopneumothorax. A chest tube drainage was performed, and hemorrhagic plueral effusion of 1,600 ml was drained. Because of this, the patient was transferred to the emergency center of our hospital. Following a blood transfusion, we continued to treat conservatively for nine days, because no more bleeding was recognized. On day ten, the patient suddenly started bleeding again, thus, an emergency operation was performed. At the operation under a thoracoscope, a bleeding point was ligated with surgical clip, however, it was difficult to remove blood clots that were attached with the lung surface, it was impossible to continue the thoracoscopic surgery. If re-bleeding occurs after the acute phase, problems may arise from conservative treatment. So, early surgical treatment should be considered.

Adult↗
PubMed1999

Mutational analysis of the cardiac actin gene in familial and sporadic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) results in part from genetic disorders. Recently, missense mutations of the cardiac actin gene have been reported to cause DCM. We studied 136 Japanese DCM cases to elucidate how frequently the gene mutations are involved in its pathogenesis. Genomic DNA samples were obtained from 136 DCM cases (107 males, 29 females), containing 30 familial DCM (5 confirmed and 25 suspected). All six exons of the cardiac actin gene were analyzed by polymerase chain reaction, single-strand conformation polymorphism, and sequencing. We detected no mutations of the disease causation previously reported (G867A or A1014G) but two silent mutations (G979C and C1018T) in exon 6 and one point mutation (T1080A) in the 3'-untranslated region. As a result of screening 128 healthy subjects, these novel silent mutations were found to be mere genetic polymorphisms, not responsible for the disease. Although some genetic polymorphisms exist in the cardiac actin gene, mutations of the gene are rarely responsible for DCM, at least in the Japanese patients.

3' Untranslated Regions↗
PubMed1999

Prevalence, predictors, and prognosis of reversal of maladaptive remodeling with intensive medical therapy in idiopathic dilated cardiomyopathy.

Some recent trials have shown that angiotensin-converting enzyme (ACE) inhibitors and/or beta blockers can improve left ventricular (LV) function and decrease LV mass in patients with idiopathic dilated cardiomyopathy (IDC). We assessed the prevalence and predictors of patients with IDC that showed marked reverse remodeling (a decrease in LV end-diastolic dimension > or = 5 mm to a final LV end-diastolic dimension < or = 55 mm and an increase in percent LV fractional shortening > or = 5% to a final percent fractional shortening of > or = 25% and a decrease in LV mass > or = 10%) after 2 years of intensive therapy with ACE inhibitors and/or beta blockers. In 78 patients with IDC (mean age 51 +/- 14 years), the clinical, echocardiographic, hemodynamic, laboratory, and endomyocardial biopsy data were evaluated at diagnosis and serial echocardiography was performed for 2 years. After 2 years of therapy, 20 of 78 patients (26%) showed marked reverse remodeling. Multivariate analysis revealed that higher systolic blood pressure (135 +/- 17 vs 120 +/- 16 mm Hg, p <0.001) and lower pulmonary arterial wedge pressure (7 +/- 3 vs 12 +/- 8 mm Hg, p <0.01) at diagnosis were independent predictors of reverse remodeling. Then, we further analyzed the prognosis of these patients for a mean of 50 +/- 32 months; 5-year survival (p <0.02) and event-free rates (p = 0.001) were better in patients with reverse remodeling than in patients without reverse remodeling.

Adrenergic beta-Antagonists↗
PubMed1999

Cloning and characterization of novel mouse and human secretory phospholipase A(2)s.

Mammalian secretory phospholipase A(2)s (sPLA(2)s) are classified into several groups according to molecular structure and the localization of intramolecular disulfide bridges. Among them, group IIA sPLA(2) has been thought to be one of the key enzymes in the pathogenesis of inflammatory diseases owing to its augmented expression under various inflammatory conditions. However, in a number of inbred mouse strains, the group IIA sPLA(2) gene is naturally disrupted by a frameshift mutation. Here, we report the cloning of a cDNA encoding a novel sPLA(2) expressed in the spleen of group IIA sPLA(2)-deficient mouse. We also cloned its human homolog and mapped its gene location on chromosome 1p36.12 near the loci of group IIA and V sPLA(2) genes. The human mature sPLA(2) protein consists of 125 amino acids (M(r) = 14,500) preceded by a 20-residue prepeptide and is most similar to group IIA sPLA(2) with respect to the number and positions of cysteine residues as well as overall identity (48%). Based on these structural properties, the novel sPLA(2) should be categorized into group II, called group IID to follow the already identified IIA to IIC sPLA(2)s. When the cDNA was expressed in COS-7 cells, PLA(2) activity preferentially accumulated in the culture medium. It is maximally active at neutral to alkaline pH and with 2 mM Ca(2+). In assays with individual substrates, L-alpha-1-palmitoyl-2-linoleoyl phosphatidylethanolamine was more efficiently hydrolyzed than the other phospholipids examined. An RNA blot hybridized with the cDNA exhibited two transcripts (2.0 and 1.0 kb) in human spleen, thymus, and colon. The expression of a novel sPLA(2) mRNA was elevated in the thymus after treatment with endotoxin in rats as well as in group IIA sPLA(2)-deficient mice, suggesting its functional role in the progression of the inflammatory process.

Amino Acid Sequence↗
PubMed1999

Suppression of murine endotoxic shock by sPLA2 inhibitor, indoxam, through group IIA sPLA2-independent mechanisms.

Endotoxic shock is a systemic inflammatory process, involving a variety of proinflammatory mediators. Two types of secretory phospholipase A2 (sPLA2) have been implicated in this process. Group IB sPLA2 (PLA2-IB) binds to the PLA2 receptor (PLA2R), and PLA2R-deficient mice exhibit resistance to endotoxin-induced lethality with reduced plasma levels of proinflammatory cytokines, such as TNF-alpha. Group IIA sPLA2 (PLA2-IIA) is found in many tissues and cell types, and local and systemic levels are elevated under numerous inflammatory conditions including sepsis. In this study, we investigated the effect of a specific sPLA2 inhibitor, indoxam, on murine endotoxic shock. Indoxam suppressed the elevation of plasma TNF-alpha with a similar potency in PLA2-IIA-expressing and PLA2-IIA-deficient mice after LPS challenge. In PLA2-IIA-deficient mice, indoxam also suppressed the elevation of plasma IL-1beta, IL-6 and NO, and prolonged survival after LPS challenge. Indoxam was found to block the PLA2-IB binding to murine PLA2R with a high potency (Ki=30 nM). The inhibitory effects of indoxam on the LPS-induced elevation of plasma TNF-alpha levels could not be observed in mice deficient in PLA2R. These findings suggest that indoxam blocks the production of proinflammatory cytokines during endotoxemia through PLA2-IIA-independent mechanisms, possibly via blockade of the PLA2R function.

Animals↗
PubMed1999

Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2.

Transcription factors with a basic helix-loop-helix (HLH) motif have been shown to be crucial for various cell differentiation processes during development of multicellular organisms. Id proteins inhibit the functions of these transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains. Members of the Id family also promote cell proliferation, implying a role in the control of cell differentiation. Here we show that Id2 is indispensable for normal development of mice. Id2-/- mice lack lymph nodes and Peyer's patches. However, their splenic architecture is normal, exhibiting T-cell and B-cell compartments and distinct germinal centres. The cell population that produces lymphotoxins, essential factors for the development of secondary lymphoid organs, is barely detectable in the Id2-/- intestine. Furthermore, the null mutants show a greatly reduced population of natural killer (NK) cells, which is due to an intrinsic defect in NK-cell precursors. Our results indicate that Id2 has an essential role in the generation of peripheral lymphoid organs and NK cells.

Animals↗
PubMed1999

The leukemic oncogene tal-2 is expressed in the developing mouse brain.

tal-1 (T-cell acute leukemia-1; also known as SCL) and tal-2 genes belong to a family of basic helix-loop-helix transcription factors and were originally isolated from the breakpoints of chromosomal translocations in human T-cell leukemia cell lines. tal-1 is expressed not only in hematopoietic cells but also in several endothelial structures and the central nervous system during development. On the other hand, the detailed function and the sites of expression of tal-2 have remained obscure. We cloned the tal-2 cDNA from a mouse embryonic cDNA library and examined its expression pattern in the mouse, comparing with that of tal-1. In situ analyses revealed that tal-2 transcripts are detected at embryonic day 12.5 in the following regions; 1) the diencephalon-the zona limitans intrathalamica and the pretectum, 2) the mesencephalon-the tectum, and the anterior and posterior tegmentum, 3) the metencephalon-the isthmus and the anterior pons. In the diencephalon and the mesencephalon, the expression sites of tal-2 gene were similar to those of tal-1, and its expression was stronger than that of tal-1. In the metencephalon, tal-2 expression was observed in the anterior pons, whereas tal-1 transcripts were detected in the entire pons, and showed stronger expression than tal-2. The tal-2 messages were barely detectable in the brain at birth. These results suggest that tal-1 and tal-2 are involved in the development of specific areas of the central nervous system.

Amino Acid Sequence↗
PubMed1999

Evaluation of immune responses to inactivated influenza vaccines prepared in embryonated chicken eggs and MDCK cells in a mouse model.

This study was initiated with the isolation of influenza A and B viruses from clinical throat swabs in both fertile chicken eggs (egg) and MDCK cells, which were used in subsequent vaccine production in the above two hosts. On the basis of haemagglutination-inhibiting (HI) tests, immune mouse sera from mice vaccinated with MDCK cell-derived vaccines revealed antigenic similarities among H3N2 or B viruses isolated in MDCK cells or eggs. Similarly, antiserum prepared by immunization with egg-derived H3N2 vaccine showed equivalent antigenicity between homologous and heterologous (MDCK cell-derived) viruses. In contrast, antigenicity of egg-derived B vaccines was differed somewhat from that of MDCK cell-derived vaccines, suggesting the occurrence of antigenic change due to passaging in eggs. The time-course of immune responses based on HI titres indicated that MDCK cell-derived vaccines elicited extremely high antibody levels. Also, it was evident that antibody production by MDCK cell-grown H3N2 vaccine was very similar to that of vaccine prepared from egg-grown viruses. These results were comparable to those of plaque neutralization tests, although antigenic differences between egg- and MDCK cell-derived challenge viruses were confirmed in the test with antiserum to MDCK cell-derived vaccine. Consistent with HI-antibody production, the immunogenicity of MDCK cell-derived B vaccine appeared to be low by plaque neutralization test, while immune responses in mice which received egg-derived vaccines were significantly higher than that of the former. Furthermore, immune responses confirmed in mice immunized with B virus vaccines prepared in eggs revealed slight antigenic differences between two viruses derived from their respective hosts. Nevertheless, through evaluation of immune responses, MDCK cell-derived influenza vaccines may be useful when weak immunogenicity of B virus vaccine is improved.

Animals↗
PubMed1998

Low prevalence of Helicobacter pylori infection in patients with hamartomatous fundic polyps.

Helicobacter pylori infection of the gastric mucosal surface was investigated in patients with hamartomatous fundic polyps or hyperplastic polyps and in patients without endoscopic evidence of disease (healthy subjects). Presence of H. pylori infection was determined by culture, histologic examination, and the endoscopic phenol red test. Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral biopsy specimens. Both prevalence of H. pylori infection (P < 0.001) and H. pylori adherence (P < 0.05) were less in patients with hamartomatous fundic polyps than in healthy subjects and patients with hyperplastic polyps. However, the percentages of plasma cells in gastric mucosa that contained IgA and of gastric epithelial cells that expressed Lewis b did not differ significantly among the three groups. These findings suggest that defense mechanisms against the attachment of H. pylori other than IgA or Lewis b antigen are present in patients with hamartomarous fundic polyps.

Biopsy↗
PubMed1998

A protein of the basal lamina of the sea urchin embryo.

The purification, biochemical characterization and functional features of a novel extracellular matrix protein are described. This protein is a component of the basal lamina found in embryos from the sea urchin species Paracentrotus lividus and Hemicentrotus pulcherrimus. The protein has been named Pl-200K or Hp-200K, respectively, because of the species from which it was isolated and its apparent molecular weight in SDS-PAGE under reducing conditions. It has been purified from unfertilized eggs where it is found packed within cytoplasmic granules, and has different binding affinities to type I collagen and heparin, as assessed by affinity chromatography columns. By indirect immunofluorescence experiments it was shown that, upon fertilization, the protein becomes extracellular, polarized at the basal surface of ectoderm cells, and on the surface of primary mesenchyme cells at the blastula and gastrula stages. The protein serves as an adhesive substrate, as shown by an in vitro binding assay where cells dissociated from blastula embryos were settled on 200K protein-coated substrates. To examine the involvement of the protein in morphogenesis of sea urchin embryo, early blastula embryos were microinjected with anti-200K Fab fragments and further development was followed. When control embryos reached the pluteus stage, microinjected embryos showed severe abnormalities in arms and skeleton elongation and patterning. On the basis of current results, it was proposed that 200K protein is involved in the regulation of sea urchin embryo skeletogenesis.

Animals↗
PubMed1998

Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum.

BACKGROUND: Serrated adenoma is a new morphological subtype of colorectal adenoma. The lesion provides a distinct morphological route to carcinoma, but the underlying genetic changes have not yet been investigated. AIMS: To determine the frequency of K-ras mutation in serrated adenoma. METHODS: The frequency of K-ras codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: Although most of the serrated adenomas were large (average size 11.4 mm) and polypoid, K-ras codon 12 point mutation was detected in only one of the 20 (5%), which is a significantly lower frequency than that in sporadic polypoid adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of carcinoma in situ, indicating their malignant potential and the existence of a serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of carcinoma in situ. CONCLUSIONS: K-ras mutation is uncommon in serrated adenomas, indicating a different spectrum of genetic alterations in these lesions from those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma represents a new genetic pathway in the histogenesis of colorectal carcinoma.

Adenoma↗
PubMed1998

Diabetes mellitus and cardiomyopathy--association with mutation in the mitochondrial tRNA(Leu)(UUR) gene.

In this report, cardiac abnormalities in 2 diabetic patients with a mutation in the mitochondrial tRNA(Leu)(UUR)gene are described. The 2 patients exhibited left ventricular dilation and diffuse decreased wall motion. Cardiac catheterization studies revealed normal coronary angiography. In both patients, light microscopic examination of hematoxylin and eosin-stained sections revealed myocyte hypertrophy and perinuclear vacuolization and electron microscopy revealed an increase in the number and size of mitochondria and abnormal configuration of cristae. These findings suggest that mutations in mitochondrial DNA, such as an A-->G mutation at position 3243, should be considered as a cause not only of diabetes mellitus but also of cardiac involvement in patients with diabetes mellitus.

Cardiomyopathies↗