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Biomedical subjects

K Sakata

Publications and source records attributed to K Sakata.

At least 181 records · Page 10Linked to original sources

Difference of hyaluronidase produced by human tumor cell lines with hyaluronidase present in human serum as revealed by zymography.

Human carcinoma cells cultured in serum free medium produced an enzyme present as two different isoforms of 62 and 59 kDa which was found to degrade hyaluronan and chondroitin sulfate, with optimum activity at pH 4.0 and 0.03 M NaCl. The activity was suppressed by treatment with 250 mM apigenin and 1 mM DTT. The one-dimensional and two-dimensional gel patterns of tumor hyaluronidase differed from those of human serum hyaluronidase. Deglycosylation of tumor hyaluronidase caused nearly complete elimination of activity, suggesting the importance of sugar chains in enzymatic function. The results of treatment with neuraminidase, in addition to the findings for the enzyme mentioned above, suggest hyaluronidase from carcinoma cells and serum hyaluronidase to differ in sugar chains and/or the core protein. Tumor hyaluronidase was shown to be endo-beta-N-acetyl-D-hexosaminidase and tetrasaccharide was identified as the major product, thus indicating the tumor hyaluronidase to be a testis-type hyaluronidase.

Blood Proteins↗

Clinical and prognostic significance of atrial fibrillation in acute myocardial infarction.

The clinical significance of the time of onset of atrial fibrillation (AF) was investigated in patients with acute myocardial infarction (AMI). Among 1,039 patients with AMI, 100 (9.6%) had AF. These patients were divided into 3 groups: AF group 1 (n = 45), who developed AF within 24 hours of the onset of AMI; AF group 2 (n = 41), who developed AF >24 hours after the onset of AMI; and AF group 3 (n = 14), who developed AF before the onset of AMI. The infarct-related lesion was most frequent (67%) in the proximal right coronary artery in AF group 1 (p <0.01). Right atrial pressure was most significantly increased in AF group 1. The left atrial dimension and pulmonary arterial wedge pressure were most significantly increased, and left ventricular ejection fraction was most significantly decreased in AF group 2. In the acute phase, the frequencies of heart failure, cardiogenic shock, and in-hospital mortality were higher for all 3 AF groups than the sinus group (p <0.01). The long-term survival rate was significantly lower in AF group 1 and AF group 2 than in the sinus group. AF was an independent predictor of cardiac death in both AF group 1 (odds ratio 2.5; 95% confidence interval 1.2 to 5.0; p = 0.0012) and AF group 2 (odds ratio 3.7; 95% confidence interval 1.8 to 7.5; p = 0.0005), but not in AF group 3. The onset time of AF appears to be a useful parameter for evaluating the cardiac status and prognosis of patients with AMI.

Aged↗

A novel RING finger protein, BFP, predominantly expressed in the brain.

RING finger is a variant zinc finger motif present in a new family of proteins including transcription regulators. A genomic DNA fragment containing RING finger motifs was identified by the polymerase chain reaction using degenerate primers. Using this fragment as a probe, we have isolated a novel cDNA from rat brain library. The predicted open reading frame contains a RING finger domain at its N-terminal portion. The corresponding transcript was detected predominantly in the brain and therefore was designated brain finger protein (bfp). An antibody raised against a recombinant bfp reveals the presence of the bfp in the brain. Interestingly, the bfp is induced during retinoic acid-mediated differentiation of P19 embryonal carcinoma cells into neural cells. These findings suggest the possible involvement of bfp in some aspects of neural cell regulation.

Amino Acid Sequence↗

Characterization of glycine release mediated by glycine transporter 1 stably expressed in HEK-293 cells.

We constructed a cell line which stably expresses glycine transporter 1 (GlyT1) proteins. The cell line showed significant [14C]glycine uptake and could keep steep glycine concentration gradient between intracellular and extracellular space (in > out). Using this cell line, we investigated glycine release mediated by this transporter. The [14C]glycine release was enhanced by extracellular glycine and sarcosine, a selective inhibitor of the transporter, in a dose-dependent manner. In addition, the replacement of extracellular Na+ with Li+ or extracellular Cl- with acetate- markedly increased the release. Furthermore, we investigated the effects of extracellular Ca2+ and K+. The removal of these ions also showed enhancement of the release. These results suggest that glycine transporter 1 protein, which might be involved in the NMDA receptor neurotransmission, can release glycine into the extracellular space in the vicinity of synapses, and that the release might be influenced by the extracellular substrate concentration and ion composition in the synaptic cleft.

Amino Acid Transport Systems, Neutral↗

Identification of regulatory region of antizyme necessary for the negative regulation of polyamine transport.

Antizyme is a negative regulator of ornithine decarboxylase (ODC) and of polyamine transport. Regions of antizyme necessary for the negative regulation of polyamine transport were determined by transfecting ODC-overproducing EXOD-1 cells with mutant antizyme genes containing different size deletions in the NH2- and COOH-terminal of antizyme (AZ69-227). When peptide 119-144 or peptide 211-216, which are responsible for the binding of ODC, were deleted from antizyme, the mutant antizyme could not reverse the inhibition of growth of EXOD-1 cells produced by spermine. In parallel with the decrease in antizyme effect on cell growth, spermine transport activity and the accumulation of spermine in EXOD-1 cells were not significantly altered by the mutant antizyme, whereas wild-type antizyme decreased spermine transport and accumulation. When the peptide 69-118, which is responsible for the degradation of ODC, was deleted from antizyme, the mutant antizyme showed a smaller effect compared with the normal antizyme in terms of the inhibition of spermine transport and the recovery from the spermine inhibition of cell growth. The results indicate that regions 119-144 and 211-216 in antizyme are necessary for the negative regulation of polyamine transport and that these regions overlap with ODC binding sites.

Amino Acid Sequence↗

Prognostic significance of a clearly audible fourth heart sound detected a month after an acute myocardial infarction.

Patients (n = 181) with a myocardial infarction, with (n = 20) or without (n = 161) a clearly audible fourth heart sound detected 1 month after the onset of a myocardial infarction, were followed for 56.2 +/- 21.4 months for cardiac events (death, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass surgery, worsening angina, or heart failure). The present study suggests that a clearly audible fourth heart sound detected 1 month after the onset of myocardial infarction increases the risk of adverse cardiac events.

Aged↗

Prognostic value of Doppler transmitral flow velocity patterns in acute myocardial infarction.

Doppler transmitral flow patterns are partially dependent on age. We investigated the correlations between the age-adjusted transmitral flow patterns, hemodynamic indexes, and the coronary and clinical outcome in 206 patients with acute myocardial infarction (AMI) and 102 normal control subjects. The peak flow velocity at atrial contraction was significantly lower in 50 of the 206 patients (24%) (low-A group) than in the 102 normal controls. Pulmonary capillary wedge pressure was significantly higher in the low-A group than in the remaining 156 patients with AMI (20 +/- 7 vs 11 +/- 5 mm Hg, p <0.001), and the cardiac index and left ventricular ejection fraction were significantly lower (2.2 +/- 0.6 vs 2.9 +/- 0.7 L/min/m2, p <0.001; 38 +/- 15% vs 52 +/- 13%, p <0.001). The incidence of cardiogenic shock was significantly higher in the low-A group than in the other patients with AMI (42% vs 19%, p <0.001). Regression analysis demonstrated a significant association between decreased atrial filling velocity and increased in-hospital mortality as well as the incidence of heart failure in AMI (p <0.001). The 5-year mortality rate was also significantly higher in the low-A group (p <0.001). The age-adjusted transmitral flow pattern in AMI can identify patients with left ventricular dysfunction, which can lead to a poor prognosis.

Adult↗

Left ventricular fibroma in an aged patient: report of a case.

We report herein the case of a 77-year-old man with a left ventricular tumor originating from the papillary muscle of the left ventricular wall, in whom a successful tumor resection with mitral valve replacement was performed. The pathological diagnosis of the tumor was confirmed as cardiac fibroma. His postoperative course was uneventful and he is currently well with no signs of recurrence 2 years after surgery.

Aged↗

Assessment of regional sympathetic nerve activity in vasospastic angina: analysis of iodine 123-labeled metaiodobenzylguanidine scintigraphy.

With the use of iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy, this study evaluated regional sympathetic nerve activity in vasospastic angina. Twenty male patients with left anterior descending coronary artery spasm and 18 male patients with normal coronary arteries as a control group were studied. All patients underwent quantitative 123I-MIBG scintigraphy and atropine stress 123I-MIBG scintigraphy. Both groups showed a similar heterogeneous 123I-MIBG uptake in the left ventricle. However, the regional washout rate in patients with coronary artery spasm was significantly reduced in all three territories compared with that in the control group. In vasospastic angina, the regional washout rate in the left anterior descending coronary artery territory was significantly reduced as compared with the other two regions. After intravenous injection of 1 mg atropine, the regional washout rate in the three regions significantly increased in both groups, but the regional differences between the two groups disappeared. The current study demonstrated that cardiac sympathetic nerve activity in vasospastic angina was suppressed, especially in the territory of the spasm-induced coronary artery, probably because of the enhanced parasympathetic nerve activity.

3-Iodobenzylguanidine↗

Iodine-123 metaiodobenzylguanidine cardiac imaging to identify and localize vasospastic angina without significant coronary artery narrowing.

OBJECTIVES: We assessed the ability of iodine-123 metaiodobenzylguanidine (MIBG) imaging to identify and localize coronary spasm and determined the most useful method of MIBG analysis in vasospastic angina without significant coronary narrowing. BACKGROUND: Various noninvasive methods have been used to detect vasospastic angina, but they are not very sensitive in patients with sporadic attacks. MIBG imaging has recently been proposed as a useful tool for detecting vasospastic angina. METHODS: Normal limits of both visual and quantitative analysis of two-dimensional polar maps (bull's-eyes) for MIBG imaging were at first established in 59 normal subjects. For optimal criteria of visual analysis, we established regional differences in abnormal MIBG defect scores. An abnormal region of the bull's-eye was defined as an area > 2 SD below normal. An abnormal regional washout rate was defined as < 0%. Using these criteria, we prospectively evaluated 104 patients with suspected vasospastic angina. Visual, bull's-eye and regional washout rate analyses were compared for overall detection of the disease and for individual vessel involvement. RESULTS: Overall sensitivity by these methods was 30%, 42% and 76%, respectively. Washout rate analysis showed a significantly higher sensitivity than the other two methods. Specificity was 78%, 72% and 87%, respectively. The sensitivity of detecting spasm-induced coronary artery with washout rate analysis was 82% for the left anterior descending (LAD), 76% for the right (RCA) and 69% for the circumflex (Cx) coronary arteries. The sensitivity of visual analysis was 29%, 15% and 35%, respectively; that for bull's-eye analysis was 34%, 54% and 41%, respectively. Washout rate analysis showed a significantly higher sensitivity for LAD spasm than for the other two methods and a higher sensitivity for RCA and Cx spasms than for visual analysis. CONCLUSIONS: Regional washout rate analysis of MIBG imaging is a highly accurate technique for determining the presence and location of coronary artery spasm.

3-Iodobenzylguanidine↗

Characterization of fertilization-blocking monoclonal antibody 1G12 with human sperm-immobilizing activity.

A mouse hybridoma (1G12) producing sperm-immobilizing MoAb to human sperm was established and characterized in order to study the antigens relevant to sperm immobilization by antibodies. MoAb 1G12 had strong sperm-immobilizing and agglutinating activities and also showed a fertilization-blocking activity on in vitro fertilization tests. The antibody absorption experiments showed that MoAb 1G12 reacted not only to ejaculated sperm but also human seminal plasma, suggesting that the corresponding antigen might be a sperm coating antigen. The MoAb also reacted with peripheral blood lymphocytes. In histochemical studies, the epithelia of corpus epididymis were most strongly stained. Ejaculated sperm were stained with a granular pattern for their entire surface by immunofluorescence. MoAb 1G12 recognized polymorphic glycoproteins of 15-25 kD in the ejaculated sperm extract in Western blot analysis. After deglycosilation of the sperm extract, only a single staining band of under 15 kD was detected by MoAb 1G12. This suggests that the antigen epitope recognized by MoAb 1G12 might be a peptide of the core portion of the glycoprotein. MoAb 1G12 might be a useful tool for studying the mechanism of egg-sperm interaction, and also be applied to identifying the corresponding antigen by using gene technology.

Absorption↗

Long survival of patients with unresectable cervical carcinoma after radiotherapy.

We report our experience with radiotherapy for three patients with cervical carcinoma in whom surgery had been downgraded to the performance of exploratory laparotomy only, because of extensive primary tumor or nodal invasion to the surrounding organs and vessels. Tumor invasion to the bladder, side wall invasion or unresectable nodal disease at the time of exploration prevented definitive surgery in our case series. After laparotomy, we carried out radiation therapy consisting of external irradiation to the pelvis and intracavitary irradiation with high dose rate 60Co or low dose rate 137Cs sources. Local and regional control was obtained in all three patients, and there was no locoregional recurrence during > 5 years of follow-up. One patient died of paraaortic lymph node metastases, but she had no pelvic recurrence. Several authors have reported an increased risk of small bowel obstruction in patients who undergo laparotomy before radiotherapy. None of our patients developed small bowel obstruction, although one had anal bleeding which was cured by conservative therapy. Radiotherapy was effective for locoregional control in all three patients with unresectable cervical carcinoma.

Aged↗

Analysis of the DPC4 gene in gastric carcinoma.

Allelic loss on chromosome 18q is involved in the progression of gastric carcinoma. Recently, DPC4 (deleted in pancreatic carcinoma, locus 4), a candidate tumor suppressor gene, has been localized at 18q21.1. This gene is inactivated in nearly one half of pancreatic carcinomas. We tested for DPC4 gene mutations and allelic status at 18q21 in 30 primary gastric carcinomas and 5 gastric carcinoma cell lines. Polymerase chain reaction single-strand conformation polymorphism and sequencing analyses revealed no DPC4 mutations in any of the primary tumors or cell lines. Homozygous deletion of DPC4 was observed in only 1 (MKN-45) of the 5 (20%) cell lines. This suggests that the target gene for loss on 18q is not DPC4. The true tumor suppressor gene, encoded near DPC4, has yet to be identified.

Chromosome Deletion↗

MAD-related genes on 18q21.1, Smad2 and Smad4, are altered infrequently in esophageal squamous cell carcinoma.

The MAD (mothers against decapentaplegic)-related genes, Smad2 (former name MADR2 or JV18-1) and Smad4 (former name DPC4), have been identified on chromosome 18q21.1. We analyzed 30 primary esophageal squamous cell carcinomas (ESCC) and 7 cell lines derived from ESCC for intragenic mutations and loss of heterozygosity (LOH) of the Smad2 and Smad4 genes. LOH was detected in 5 of 14 (35%) informative cases. However, no mutations in either gene were detected in either the primary carcinomas or the cell lines, and only a G-to-A base transition within the 3'-untranslated region of the Smad4 gene was observed in a carcinoma. There were no homozygous deletions in either of the genes in the cell lines. MAD-related genes on chromosome 18q21.1 are altered infrequently in ESCC.

Carcinoma, Squamous Cell↗

DNA analysis of the androgen receptor gene in two cases with complete androgen insensitivity syndrome.

OBJECTIVE: Androgen insensitivity syndrome is an X-linked disorder of sexual differentiation resulting from abnormalities of the androgen receptor gene. In this study, we analyzed the androgen receptor gene in 2 cases with complete androgen insensitivity syndrome (CAIS). METHODS: DNAs were isolated from patients with CAIS, and the androgen receptor gene was amplified by a polymerase chain reaction. Sequence analysis of the androgen receptor gene was performed. RESULTS: In Patient 1, one substitutional mutation [glutamine (CAA) to arginine (CGA) at position 194] was identified in exon A, and the premature termination of the androgen receptor gene was also demonstrated due to the deletion of one nucleotide at the codon in exon C (position 597). In Patient 2, one substitutional mutation [arginine (CGC) to cysteine (TGC) at position 855] in exon G was identified. This position was located in the hormone-binding domain and appeared to be a hot spot of mutations because the mutations at the same position have been reported before in several unrelated cases. CONCLUSION: The results of this study suggest that these abnormalities might be related to the pathogenesis of complete androgen insensitivity syndrome.

Adult↗

Aggressive angiomyxoma of the scrotum.

Aggressive angiomyxoma is a rare benign tumor, arising in the pelvic soft tissues and perineum. It occurs almost exclusively in adult females. It is locally infiltrative and exhibiting a high risk of local recurrence. However, it is slow growing and does not metastatize. We report a case of aggressive angiomyxoma in an adult male which arose in the scrotum.

Genital Neoplasms, Male↗

Treatment of lethal midline granuloma type nasal T-cell lymphoma.

Nasal T-cell lymphoma of the LMG type (LMG-NTL) is characterized by progressive, unrelenting ulceration, and necrosis of the nasal cavity and midline facial tissues. The clinical behavior of this tumor in 16 patients is compared with that of a nasal lymphoma of non-LMG-NTL type (non-LMG-NTL) in 8 patients and a paranasal sinus lymphoma (PSL) in 6 patients. All patients had stage I or II disease. Fourteen of the 16 patients with LMG-NTL received chemotherapy before and/or after radiotherapy. Cause-specific 5-year survival rates for patients with LMG-NTL, non-LMG-NTL, and PSL were 22%, 75%, and 67% respectively. Seven patients with LMG-NTL, had complete response, although 3 recurred, whereas it was incomplete in 9 patients. The data indicates that it is desirable to deliver 50 Gy or more to achieve in-field control of LMG-NTL.

Adult↗