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Biomedical subjects

T Yasuda

Publications and source records attributed to T Yasuda.

At least 145 records · Page 8Linked to original sources
PubMed2000

Cavernous sinus invasion and tumor proliferative potential of growth hormone-producing pituitary tumors.

PURPOSE: Surgical removal of growth hormone-producing pituitary adenomas (GHomas) becomes difficult when they invade the cavernous sinus (CS). We investigated the relation among tumor proliferative potential, tumor volume and invasion of GHomas to CS. MATERIALS & METHODS: 15 patients with GHoma aged 20-59 years were enrolled. The volumes of the adenomas were calculated from MR images and the extension to CS was classified into 5 grades according to Knosp's grading system. The immuno-histochemical staining for anti-Ki-67 monoclonal antibody (MIB-1) was performed and the proliferative potential of GHomas was determined as the percentage of MIB-1 labeled nuclei (MIB-1 index). The volume, MIB-1 index and pre-operative growth hormone (GH) level were compared with CS invasion by single and multiple regression analyses. RESULTS: With single regression analyses, CS invasion was significantly correlated with both the volume (r=0.69, p<0.01) and MIB-1 index (r=0.73, p<0.01), but not with the GH level (r=0.42, p=0.12). The volume and MIB-1 index showed a weak correlation but it was not significant (r=0.52, p=0.06). With multiple regression analysis, CS invasion was well explained by the volume and MIB-1 index of GHomas (r=0.82, p<0.01). About 66% of CS invasion was explained by these two factors. CONCLUSIONS: In view of these results, not only the volume but also the speed of growth are important for GHomas to invade CS. GHomas with a high MIB-1 index may, even if they are small, more readily invade CS and need closer post-operative hormonal and neuroimaging studies.

Adenoma↗
PubMed2000

Identical twins with long QT syndrome associated with a missense mutation in the S4 region of the HERG.

Familial long QT syndrome (LQTS) is caused by mutations in genes encoding ion channels important in determining ventricular repolarization. Mutations in at least five genes have been associated with the LQTS. Fire genes, KCNQ1, HERG, SCN5A, KCNE1, and KCNE2, have been identified. We have identified a missense mutation in the HERG gene in identical twins in a Japanese family with LQTS. The identical twins in our study had QT prolongation and the same missense mutation. However only the proband had a history of syncope. Although many mutations in LQT genes have been reported, there are few reports of twins with LQTS. This is the first report, to our knowledge, of identical twins with a HERG gene mutation.

Adult↗
PubMed2000

Molecular cloning of cDNA encoding Xenopus laevis deoxyribonuclease I.

A 1200-bp cDNA encoding Xenopus laevis deoxyribonuclease I (X. laevis DNase I) was constructed from the total RNA of a X. laevis pancreas using a rapid amplification of cDNA ends method. When the cDNA was transiently transfected into COS-7 cells, the recombinant polypeptide exhibited similar enzymological properties to those of the native pancreatic DNase I. The recombinant enzyme was considerably more labile than most other vertebrate DNase I enzymes. The X. laevis DNase I polypeptide was larger than any other known vertebrate DNase I, containing a unique Cys-rich stretch of 68 or 70 amino acid residues at the carboxyl terminus, and it had less well conserved binding sites for the Ca2+, G-actin and DNA, and two DNase I signature motifs. These alterations might account for its heat instability.

Amino Acid Sequence↗
PubMed2000

[Oral allergy syndrome in patients with Japanese cedar pollinosis].

Patients with pollinosis sometimes complain of oral symptoms (itching and tingling with or without edema of the lips, mouth and tongue) after eating fresh fruits and vegetables. This condition has been termed Oral Allergy Syndrome (OAS). Twenty-three patients with Japanese cedar pollinosis and OAS for fresh fruits and vegetables were included in this study. Their mean age was 31.3 years (range = 5 to 62). The fruits that caused OAS in these patients included melon, apple, peach, and kiwi fruit. Most patients with OAS exhibited hypersensitivity to more than two foods. Specific IgE antibodies to inhaled allergens of mite, Japanese cedar pollen, birch pollen, melon, apple, peach, and kiwi were evaluated using the Pharmacia CAP system. Eleven of the 16 subjects with specific IgE antibodies for birch pollen, did not suffer symptoms during the birch and alder pollen season. In subjects with specific IgE antibodies for fruits, 13 out of 20 patients showed specific IgE antibodies for apple, and 8 out of 9 patients with OAS for apples were also positive for specific IgE antibodies for apples. On the other hand, 17 patients had no specific IgE antibodies for melon, and only two patients and one patient showed specific IgE antibodies for kiwi fruit and peach, respectively. These results suggest that the evaluation of specific IgE antibodies to birch pollen and apple may be useful for diagnosing OAS in patients with Japanese cedar pollinosis.

Adult↗
PubMed2000

Occupational lifting is associated with hip osteoarthritis: a Japanese case-control study.

OBJECTIVE: Hip osteoarthritis (OA) is a frequent cause of pain and disability in Western countries, but the disorder is less common in Japan. A case-control study in Britain found obesity, hip injury, and occupational lifting to be associated with hip OA among men and women. However, there are few epidemiological studies concerning factors associated with hip OA in Japan. We performed a comparable case-control study of the disorder in Japan, and contrasted the findings with those from Britain. METHODS: The study was carried out in 2 health districts in Wakayama Prefecture, Japan. Cases were men and women aged > or = 45 years listed for total hip arthroplasty due to OA over one year, and who did not have an established cause of secondary OA (e.g., rheumatoid arthritis, ankylosing spondylitis). For each case, a control was selected randomly from the general population and was individually matched to the case for age, sex, and district of residence. Cases and controls were interviewed with a structured questionnaire about medical history, physical activity, socioeconomic factors, and occupation. Measurements were made of height and weight. RESULTS: One hundred fourteen cases (103 women, 11 men) were compared with 114 controls. We found no relationship between obesity and hip OA (OR = 1.0, 95% CI 0.5-1.9; highest vs lowest thirds of distribution of body mass index). There was, however, a statistically significant association between occupational lifting and hip OA, such that regular lifting of 25 kg in the individual's first job (OR = 3.6, 95% CI 1.3-9.7) or of 50 kg in their main job (OR = 4.0, 95% CI 1.1-14.2) was associated with increased risk of hip OA. These associations remained after adjustment for potential confounding variables. In contrast, those subjects who spent > 2 h each day sitting during their first job were significantly less likely to have the disorder (crude OR = 0.5, 95% CI 0.3-0.9). This association also remained statistically significant after adjustment for potential risk factors. CONCLUSION: Our findings support the hypothesis that occupational physical activity, particularly the lifting of very heavy loads in the workplace at regular intervals, predisposes to hip OA in both Britain and Japan. The lack of association between obesity or hand involvement and hip OA in Japan suggests that the contribution of constitutional and mechanical risk factors to this disorder might differ in different populations. However, attention to manual handling in the workplace would appear an important aspect of preventive strategies against hip OA in Western and Oriental populations.

Aged↗
PubMed2000

[Tracheal mucosal bulla found on tracheal extubation in a patient with pemphigus vulgaris--a case report].

A 49-year-old female with pemphigus vulgaris underwent the removal of a meningioma under general anesthesia. Neither bulla nor erosion was observed on her skin and oral cavity mucosa. She had been on prednisolone 15 mg for six years daily to avoid the recurrence of skin lesion. Anesthesia was induced and maintained with total intravenous anesthesia with propofol and fentanyl. No adverse episodes were encountered during the operative procedure. We checked the tracheal mucosa using bronchofiberscope before extubation. A small bulla was found on the tracheal mucosa, where the cuff of the tracheal tube was located. The trachea was extubated slowly under bronchofiberscopic observation, and no other bullae were found. It would have been formed by mechanical stimulation of the tracheal tube. This case suggests that we have to pay careful attention to the formation of bullae at any part of the body by mechanical stimuli during anesthetic management of patients with pemphigus vulgaris.

Anesthesia, General↗
PubMed2000

Significance of serum type IV collagenolytic activities and gelatinase levels for detection of metastasis in murine RCT sarcoma.

We investigated the usefulness of serum type IV collagenolytic activities and gelatinase levels as diagnostic markers of metastasis in the animal model of spontaneous lung metastasis by FITC-labeled type IV collagen degradation assay and zymographic analyses. High-metastatic RCT(+) and low-metastatic RCT(-) clones were used in the present study. The mean serum type IV collagenolytic activity in the RCT(+) group started to increase from two weeks after hind limb amputation, and was 0.45 and 1.29 unit/ml at three and four weeks. These values were significantly higher than those in the control group (p < 0.01 at three weeks; p < 0.001 at four weeks). A correlation between the number of lung nodules and serum type IV collagenolytic activities in the RCT(+) group was found (r = 0.89, p < 0.001). Zymographic analyses indicated that 105-kD gelatinolytic activities of the RCT(+) group were higher than those of the RCT(-) group at three and four weeks. Thus, type IV collagenolytic activities and serum gelatinase levels might be valuable markers for the detection of metastasis.

Animals↗
PubMed2000

Detection of genetic alterations in the human gastric cancer cell lines by two-dimensional analysis of genomic DNA.

We examined genomic DNA from each of three human-derived gastric cancer cell lines, using the technique of restriction landmark genomic scanning (RLGS) which allows monitoring of approximately 2, 000 NotI landmarks. The resulting DNA spots from cancer cell DNA were compared with those in normal mucosa or gastric primary tumor. In all, 9 intense spots were detected from two of the three cancer cell lines. Two highly intensified spots were common in the two cancer cell lines and proven to be originated from DNA region containing the human c-myc proto-oncogene on chromosome 8. The degree of amplification of c-myc DNA was similar to each other and was estimated to be 60-fold as compared to those from normal mucosa DNA. On the basis of chromosome-assigned RLGS (CA-RLGS), other spots were assigned to each chromosome, such as one on chromosome 8, two each from chromosome 20, and three on one of chromosome 9-12. The remaining spot seems to be due to demethylation of a repetitive element. Twenty-four spot that were lost due to either homozygous deletion or methylation on corresponding NotI cleavage sites were commonly observed in all cancer cells. These spots were also assigned to each chromosome: one each from chromosome 2, 6, 7, 13, 14, 16, and 20, two each from chromosome 3 and 5, and nine from chromosome 9-12 by CA-RLGS. Many of the multi-copy spots corresponding to ribosomal RNA genes were greatly decreased due mainly to methylation on CpG islands along with minor rDNA variants, indicating that only minor rRNA genes may be silenced in these cancer cells. These results show that the present alterations detected by RLGS might be useful for identification of candidate genes inactivated or expressed unexpectedly in tumor development and tumor progression in the stomach.

Base Sequence↗
PubMed2000

[Use of percutaneous cardiopulmonary support (PCPS) for extended surgery in patients with T4 tumor].

Since 1991, we have performed operations for tumors invading the upper airway, left atrium or main pulmonary artery with percutaneous cardiopulmonary support (PCPS) stand by support available. Of 15 cases with PCPS stand by, 6 patients actually underwent operation using PCPS. There were three esophageal cancers invading the carina, two lung neoplasms with left atrial invasion and one neoplasm extending to the main pulmonary artery. One of three patients with esophageal cancer had massive bleeding in the trachea resulting in airway obstruction. For this patient, emergency PCPS was carried out followed by the total removal of the thoracic esophagus and combined resection of membranous portion of the carina. As a result, a substantial amount of time (6 hours) was required. The two patients with reconstruction of the carina due to esophageal cancer were also successfully treated by using PCPS. Two patients with malignant pulmonary neoplasms invading the left atrium underwent combined resection of the lung and left atrium using a combination of PCPS and ventricular fibrillation under normothermia. In conclusion, PCPS should be accepted as a standard technique for patients with advanced thoracic malignancies in whom cardiac arrest or ventilation support is thought to be necessary for the complete removal of the tumor.

Adult↗
PubMed2000

Impaired splenic erythropoiesis in phlebotomized mice injected with CL2MDP-liposome: an experimental model for studying the role of stromal macrophages in erythropoiesis.

Erythropoiesis occurs in the presence of erythropoietin (EPO) without macrophages in vitro. In hematopoietic tissues, however, erythroid cells associate closely with stromal macrophages, forming erythroblastic islands via interactions with adhesion molecules. To elucidate the role of macrophages in erythropoiesis, we selectively abrogated stromal macrophages of splenic red pulp of phlebotomized mice by injection with dichloromethylene diphosphonate encapsulated in multilamellar liposomes (CL2MDP-liposome). In the spleen, no erythropoietic activity occurred until 5 days after the treatment. Colony assay revealed that the erythropoiesis was suppressed at the level of CFU-E. The splenic erythropoietic activity gradually developed from day 6 after the treatment, when F4/80+ macrophages began to appear in the red pulp. EPO mRNA was expressed in kidney but not in liver or spleen of phlebotomized mice injected with CL2MDP-liposome, and the serum EPO concentration in these mice was higher than that in phlebotomized mice. These findings suggest that abrogation of stromal macrophages by injection with CL2MDP-liposome impairs the splenic microenvironment for erythropoiesis induced by hypoxic stress, and this may be an excellent experimental model for further characterization of the in vivo role of splenic macrophages in erythropoiesis.

Anemia↗
PubMed1999

Selective inhibition of formyl-methionyl-leucyl-phenylalanine (fMLF)-dependent superoxide generation in neutrophils by pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.

It has been shown previously that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, such as compactin, lovastatin, and pravastatin, block cholesterol synthesis, suppress lymphocyte functions, and beneficially affect atherogenesis. Recently, it was reported that compactin and lovastatin inhibit the respiratory burst of DMSO-differentiated HL-60 cells, an effect reversed by mevalonic acid. The mode of action of these inhibitors in this role is not understood fully. Thus, we studied the mechanism of inhibition of neutrophil superoxide (O2*-) generation by pravastatin and found that pravastatin at 0.5 mM inhibited the receptor-mediated tyrosine kinase (TK)-dependent pathway of O2*- generation and also luminol chemiluminescence but not the protein kinase C (PKC)-dependent or the TK- and PKC-independent pathways of O2*- generation in neutrophils. Pravastatin also inhibited the tumor necrosis factor-alpha- and formyl-methionyl-leucyl-phenylalanine-induced phosphorylation of a tyrosine of a 115-kDa protein. These effects were not reversed by mevalonate. From these results it is concluded that pravastatin inhibited receptor-mediated O2*-generation by decreasing tyrosine phosphorylation but not by inhibiting the formation of an intermediate in the biosynthesis of cholesterol.

Drug Interactions↗
PubMed1999

A novel sperm-specific hypomethylation sequence is a demethylation hotspot in human hepatocellular carcinomas.

Certain human DNA regions are strikingly undermethylated at CpG sites in sperm compared to adult somatic tissues. These sperm-specific hypomethylation sequences are thought to function early in embryogenesis or gametogenesis. By using the restriction landmark genomic scanning (RLGS) cloning method, we have isolated a novel sperm-specific hypomethylation sequence, the status of which changes during spermatogenesis, embryonal growth and differentiation. This sequence is a part of a new 'NotI repeat' consisting of a 1.4 kb repetitive unit sequence named DE-1. The sequence is GC-rich and has high homology to a CpG DNA clone that was isolated by a methyl CpG protein binding column, indicating that it was normally highly methylated. We investigated the methylation status of this sequence. In the normal genome the sequence was methylated, but in the human hepatocellular carcinoma (HCC) genome, the target sequence was demethylated at the cytosine residue of the CpG dinucleotides with high frequency (75% in the previous study). These data suggest that this regional DNA hypomethylation may play a role in both cell differentiation and hepatocarcinogenesis.

Animals↗
PubMed1999

A new allele, DNASE1*6, of human deoxyribonuclease I polymorphism encodes an Arg to Cys substitution responsible for its instability.

A new allele, DNASE1*6, of human deoxyribonuclease I (DNase I) has been discovered by isoelectric focusing: its gene product has the most cathodic pI of the six electrophoretic variants. Results of DNA sequencing, mismatched PCR-restriction fragment length polymorphism, and transient transfection of the variant construct showed that the mutant was caused by a C-T transition at nucleotide position 1826, resulting in an Arg to Cys substitution at amino acid position 185 of the mature enzyme. The variant isoenzyme, expressed in COS-7 cells, was more labile than the other types. Instability and an increase in the pI value of the variant suggest that a structural alteration, perhaps due to aberrant formation of a disulfide bond, could occur in the enzyme.

Alleles↗
PubMed1999

Identification of the catalytic subunit of cAMP-dependent protein kinase from the photosynthetic flagellate, Euglena gracilis Z.

A gene named epk2 that encodes the amino acid sequence of a protein kinase was identified from the photosynthetic flagellate, Euglena gracilis Z. Homology search and phylogenetic analysis revealed that the deduced amino acid sequence of epk2 is most similar to that of the catalytic subunit of cAMP-dependent protein kinase (PKA). Northern blot analysis showed that Euglena cells express a 1.4-kb transcript of this gene. When the EPK2 protein was coexpressed with the rat regulatory subunit of PKA in cultured mammalian cells, these two proteins were coimmunoprecipitated. The association of EPK2 and the rat regulatory subunit of PKA was not detected in the cell lysate incubated with cAMP. EPK2 immunoprecipitated from the transfected cells phosphorylated Kemptide, a synthetic peptide substrate for PKA, and the phosphorylation was inhibited by PKI, a PKA-selective protein kinase inhibitor. These results indicate that EPK2 is a PKA homologue in the photosynthetic flagellate, and this is the first evidence for the occurrence of the PKA catalytic subunit in photosynthetic organisms.

Amino Acid Sequence↗
PubMed1999

Structural requirements of a human deoxyribonuclease II for the development of the active enzyme form, revealed by site-directed mutagenesis.

Using site-directed mutagenesis, we eliminated three potential N-glycosylation sites (N86, N212, and N266) of human deoxyribonuclease II (DNase II), conserved in mammalian enzymes, and a proteolytic processing site (Q46-R47), forming a propeptide subunit of the enzyme. We expressed a series of these mutant DNase II constructs in COS-7 and Hep G2 cells. Liberation of each glycosylation site at N86 and N266 and the cleavage site interfered dramatically with expression of the intracellular and secreted DNase II activities, irrespective of cell line transfected. A chimeric mutant in which the signal peptide of the DNase II was replaced with that of human DNase I had no intracellular or secreted enzyme activity. Therefore, a simultaneous attachment of a carbohydrate moiety to N86 and N266, cleavage of the propeptide from the single DNase II precursor, and the inherent signal peptide might be required for subcellular sorting and proteolytic maturation of the enzyme.

Amino Acid Substitution↗