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Biomedical subjects

K Yuasa

Publications and source records attributed to K Yuasa.

At least 37 records · Page 2Linked to original sources

A new, simple method of making a spacer in interstitial brachytherapy for mobile tongue cancer.

OBJECTIVES: This article demonstrates a new method of making a spacer that increases the distance between the mandible and implanted radioactive sources in interstitial brachytherapy for patients with mobile tongue cancer. STUDY DESIGN: Fifty-three patients with mobile tongue cancer underwent interstitial brachytherapy with spacers made by this new technique. RESULTS: Our spacer is not difficult to create or to use. The spacer was made from a plastic splint by using thermoforming techniques and quick self-curing resin, which did not need waxing, wiring, or casting. The surface of the spacer, which comes in contact with the tongue, is smooth because it is covered with tissue-conditioning material. There were no complaints of pain from the patients. Osteoradionecrosis of the mandible developed in only 1 (1.9%) of these patients. CONCLUSIONS: This spacer is simple to make and prevented osteoradionecrosis.

Brachytherapy↗

A study of the association between the prognosis of carcinoma of the mandibular gingiva and the pattern of bone destruction on computed tomography.

OBJECTIVE: To clarify whether the pattern of bone destruction seen on CT is more closely associated with the outcome of carcinoma of the mandibular gingiva than that derived from panoramic radiographs (PR). METHOD: Axial bone window CT scans and PR of 62 patients with carcinoma of the mandibular gingiva were evaluated retrospectively by two oral radiologists for the pattern of bone destruction. Patterns were classified into the three types: erosive, invasive and mixed. The relationship between these patterns with each imaging modality and cumulative recurrence rate, cumulative metastasis rate and cumulative survival rate, calculated by the Kaplan-Meier method, were statistically analysed by the log rank test. RESULTS: The pattern of bone destruction derived from CT was closely associated with the cumulative metastasis rate (P < 0.05), the cumulative recurrence rate and the cumulative survival rate. In contrast, the pattern of bone destruction based on the PR was not associated with the cumulative metastasis rate (P = 0.43), the cumulative recurrence rate (P = 0.44), or the cumulative survival rate (P = 0.5). CONCLUSION: The prognosis of patients with carcinoma of the mandibular gingiva is more closely related to a classification derived from the pattern of bone destruction on CT rather than PR. However, the number of subjects investigated in this study was not large enough to confirm our conclusions statistically. Further studies by other investigators are therefore needed.

Adult↗

Computed tomography and ultrasonography of metastatic cervical lymph nodes in oral squamous cell carcinoma.

OBJECTIVES: To define criteria for CT and US in differentiating cervical lymph node metastases in oral squamous cell carcinoma (SCC). MATERIALS AND METHODS: CT and/or US of 230 metastatic lymph nodes and 228 benign lymph nodes in 147 patients with oral SCC were retrospectively evaluated. The CT and US findings of each lymph node were compared with the histopathological findings. A metastasis was defined on CT as a lymph node with rim or heterogeneous enhancement, or measuring 10 mm or more in the short axis, regardless of enhancement pattern, and on US as having definite internal echoes, regardless of size, or without definite internal or hilar echoes, but measuring 10 mm or more in the short axis. A lymph node with hilar echoes or a ratio of the long to short axis (L/S ratio) of 3.5 or more was considered benign. A lymph node failing to comform to any of these categories was termed questionable. RESULTS: The positive predictive value (PPV) for CT was 90.8% and the negative predictive value (NPV) was 70.4%. However, 65.7% of all lymph nodes could not be classified as either metastastic or benign. PPV for US was 96.5% and NPV was 88.1%. 25.5% of all lymph nodes could not be classified as either metastatic or benign. CONCLUSIONS: Despite limitations in detecting metastases, by including a third category 'questionable' our criteria appear clinically more useful than other current methods based on two groups only.

Adult↗

The human phosphodiesterase PDE10A gene genomic organization and evolutionary relatedness with other PDEs containing GAF domains.

PDE10A is a cyclic nucleotide phosphodiesterase (PDE) exhibiting properties of a cAMP PDE and a cAMP-inhibited cGMP PDE. The transcripts are specifically expressed in the striatum. The human gene encoding PDE10A was cloned and investigated. The PDE10A gene spanned > 200 kb and contained 24 exons. The exon-intron organization of PDE10A was different from those of PDE5A and PDE6B, although these three PDEs include two GAF domains and have similar amino-acid sequences. The promoter sequence of PDE10A was highly GC-rich and did not contain a TATA motif and a CAAT box, suggesting it is a housekeeping gene. In Caenorhabditis elegans, the C32E12.2 gene encoding a probable PDE that is 48% identical to the human PDE10A protein showed similar exon organization to PDE10A but not PDE5A and PDE6B. This, together with the phylogenic tree analysis, suggested that the ancestral gene for PDE10A existed in a lower organism such as C. elegans.

Alternative Splicing↗

Tumor recurrence criteria for postoperative contrast-enhanced computed tomography after surgical treatment of oral cancer and flap repair.

OBJECTIVE: To characterize the computed tomography (CT) findings that distinguish cancer recurrence from postoperative changes that mimic such recurrence. STUDY DESIGN: We evaluated a total of 72 CT scans from 32 patients who had undergone surgery with either pectoralis major myocutaneous flap or forearm flap. The observers evaluated the presence and pattern of enhancement, the presence of low density areas, and changes in the adipose tissue of the flap. RESULTS: A persistent zone of high attenuation over 6 months suggested the high possibility of recurrence. However, an enhancement within 6 months occurred both with the recurrent tumor and with postoperative tissue. In the patients with recurrence (n = 12), the enhanced areas were focal (n = 8) or diffuse (n = 4). Focal-type recurrence often occurred at the posterior margin. The presence of low-density areas and changes in the adipose tissue in the flap are also helpful for detecting recurrence. CONCLUSIONS: The combination of several features seen on CT images can be useful in differentiating tumor recurrence from postoperative tissue changes.

Adipose Tissue↗

Specific domain of cGMP-dependent protein kinase Ibeta but not Ialpha functions as a transcriptional activator in yeast.

Recently, cyclic GMP-dependent protein kinase (cGK) was shown to translocate to the nucleus and regulate gene transcription. To determine whether cGK I proteins function as transcriptional activators, we produced the constructs of cGK Ialpha or Ibeta fused with the DNA binding domain of the yeast transcriptional activator GAL4. Here, we demonstrate that the amino-terminal region of cGK Ibeta (amino acids 1-107) exhibits transcriptional activation in yeast. However, full-length cGK Ialpha and Ibeta and the amino-terminal region of cGK Ialpha had no transcriptional activation function. Amino acid replacement in the leucine zipper motif of the amino-terminal region of cGK Ibeta substantially reduced transcriptional activation. These results suggest that the Ibeta-specific region in cGK I proteins may interact with other proteins by way of the leucine zipper motif and has a transcriptional activation function.

Animals↗

Purification, properties, and molecular cloning of a novel Ca(2+)-binding protein in radish vacuoles.

To understand the roles of plant vacuoles, we have purified and characterized a major soluble protein from vacuoles of radish (Raphanus sativus cv Tokinashi-daikon) taproots. The results showed that it is a novel radish vacuole Ca(2+)-binding protein (RVCaB). RVCaB was released from the vacuolar membrane fraction by sonication, and purified by ion exchange and gel filtration column chromatography. RVCaB is an acidic protein and migrated on sodium dodecyl sulfate-polyacrylamide gel with an apparent molecular mass of 43 kD. The Ca(2+)-binding activity was confirmed by the (45)Ca(2+)-overlay assay. RVCaB was localized in the lumen, as the protein was recovered in intact vacuoles prepared from protoplasts and was resistant to trypsin digestion. Plant vacuoles store Ca(2+) using two active Ca(2+) uptake systems, namely Ca(2+)-ATPase and Ca(2+)/H(+) antiporter. Vacuolar membrane vesicles containing RVCaB accumulated more Ca(2+) than sonicated vesicles depleted of the protein at a wide range of Ca(2+) concentrations. A cDNA (RVCaB) encoding a 248-amino acid polypeptide was cloned. Its deduced sequence was identical to amino acid sequences obtained from several peptide fragments of the purified RVCaB. The deduced sequence is not homologous to that of other Ca(2+)-binding proteins such as calreticulin. RVCaB has a repetitive unique acidic motif, but not the EF-hand motif. The recombinant RVCaB expressed in Escherichia coli-bound Ca(2+) as evidenced by staining with Stains-all and migrated with an apparent molecular mass of 44 kD. These results suggest that RVCaB is a new type Ca(2+)-binding protein with high capacity and low affinity for Ca(2+) and that the protein could function as a Ca(2+)-buffer and/or Ca(2+)-sequestering protein in the vacuole.

Amino Acid Sequence↗

Overexpression of presenilin-2 enhances apoptotic death of cultured cortical neurons.

Presenilin-2 (PS2) is a gene of unknown function linked with some forms of familial Alzheimer's disease. To investigate the biological role of PS2 in neurons, we overexpressed PS2 in primary cortical neurons using recombinant adenoviral vectors. Western blot and immunohistochemical analyses showed enhanced expression of PS2 proteins in infected neurons after infection of recombinant adenoviruses containing the human wild-type or mutant PS2 gene. Neuronal survival was decreased by approximately 30% in cultures infected with adenovirus expressing either wild-type or mutant PS2, as compared with those infected with adenovirus expressing the LacZ gene. Fragmented nuclei were frequently observed in dying neurons. These data suggest that apoptotic death of cultured cortical neurons is enhanced by PS2 overexpression.

Animals↗

A novel interaction of cGMP-dependent protein kinase I with troponin T.

cGMP-dependent protein kinase (cGK) is a major intracellular receptor of cGMP and is implicated in several signal transduction pathways. To identify proteins that participate in the cGMP/cGK signaling pathway, we employed the yeast two-hybrid system with cGK Ialpha as bait. cDNAs encoding slow skeletal troponin T (skTnT) were isolated from both mouse embryo and human skeletal muscle cDNA libraries. The skTnT protein interacted with cGK Ibeta but not with cGK II nor cAMP-dependent protein kinase. The yeast two-hybrid and in vitro binding assays revealed that the N-terminal region of cGK Ialpha, containing the leucine zipper motif, is sufficient for the association with skTnT. In vivo analysis, mutations in cGK Ialpha, which disrupted the leucine zipper motif, were shown to completely abolish the binding to skTnT. Furthermore, cGK I also interacted with cardiac TnT (cTnT) but not with cardiac troponin I (cTnI). Together with the observations that cTnI is a good substrate for cGK I and is effectively phosphorylated in the presence of cTnT in vitro, these findings suggest that TnT functions as an anchoring protein for cGK I and that cGK I may participate in the regulation of muscle contraction through phosphorylation of TnI.

Animals↗

Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP.

We have isolated a novel alternative splice variant of human cAMP- and cGMP-hydrolyzing phosphodiesterase (PDE10A2) from human fetal lung. The N-terminal sequence of human PDE10A2 differed from that of human PDE10A1 reported previously. PDE10A1 and PDE10A2 expressed in COS-7 cells have cGMP K(m) values of 14 and 13 microM, low cAMP K(m) values of 0.28 and 0.22 microM, and high cAMP K(m) values of 0.96 and 1.1 microM, respectively, at high concentrations of cGMP and cAMP. PCR analysis demonstrated that both PDE10A1 and PDE10A2 transcripts are present in various human tissues and that PDE10A2 transcripts are a major form in some human tissues. The unique N-terminus of PDE10A2 has a putative phosphorylation site by cAMP-dependent protein kinase (cAK), but PDE10A1 does not. The recombinant PDE10A2 protein is preferentially phosphorylated by cAK, although the recombinant PDE10A1 protein is not phosphorylated by cAK.

Alternative Splicing↗

Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A).

cDNA encoding a novel phosphodiesterase (PDE) was isolated from a human fetal lung cDNA library and designated PDE10A. The deduced amino acid sequence contains 779 amino acids, including a putative cGMP binding sequence in the amino-terminal portion of the molecule and a catalytic domain that is 16-47% identical in amino acid sequence to those of other PDE families. Recombinant PDE10A transfected and expressed in COS-7 cells hydrolyzed cAMP and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with cAMP. Of the PDE inhibitors tested, dipyridamole was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of cAMP and cGMP hydrolysis, respectively. cGMP inhibited hydrolysis of cAMP, and cAMP inhibited cGMP hydrolysis with IC50 values of 14 and 0.39 microM, respectively. Thus, PDE10A exhibited properties of a cAMP PDE and a cAMP-inhibited cGMP PDE. PDE10A transcripts were particularly abundant in the putamen and caudate nucleus regions of brain and in thyroid and testis, and in much lower amounts in other tissues. The PDE10A gene was located on chromosome 6q26 by fluorescent in situ hybridization analysis. PDE10A represents a new member of the PDE superfamily, exhibiting unique kinetic properties and inhibitor sensitivity.

Amino Acid Sequence↗

Augmented proliferation of human alveolar macrophages after allogeneic bone marrow transplantation.

After allogeneic bone marrow transplantation (allo-BMT), recipient alveolar macrophages (AM) are gradually replaced by AM of the donor origin. An influx of mononuclear phagocytes of donor origin to the lung is responsible for the repopulation, but the detailed kinetics remain unclear. We therefore studied 24 BMT recipients who underwent bronchoalveolar lavage (BAL) from 24 to 83 days after BMT. AM cell number, size, morphology, proliferating ability, and genotype of AM were measured. Before day 50, the number and size of AM in BAL fluid were similar to those of normal nonsmokers. However, after day 50, the mean number of AM increased threefold and the mean cell size decreased due to the increase of small AM. These small cells are presumably of donor origin based on DNA fingerprinting analysis and based on fluorescence in situ hybridization for the Y chromosome in a sex-mismatched case. Immunohistochemistry and cell cycle analysis demonstrated that the increase in AM number coincided with a remarkable increase of AM expressing proliferating cell nuclear antigen, suggesting that small AM are proliferating. This is the first report representing that augmented proliferation of donor AM in situ may contribute to the reconstitution of AM population after BMT.

Adolescent↗

Effective adenovirus-mediated gene expression in adult murine skeletal muscle.

We established an efficient method for obtaining expression of a foreign marker gene transferred in vitro into myoblasts and in vivo into adult mouse skeletal muscles using adenovirus vector. After infection of the C2 myoblasts with the adenovirus vector containing the beta-actin promoter with cytomegalovirus (CMV) enhancer (CAG promoter) AxCALacZ, significantly greater number of cells express beta-galactosidase when compared with the adenovirus vector expressing the lacZ gene under the control of the SR alpha viral terminal repeat promoter (AxSRLacZL) or the myosin heavy chain (MHC) IIB promoter (AxMHCLacZ). We also injected AxCALacZ into the skeletal muscles of 5- to 6-week-old C57BL/10 mice and determined that more than 60% of their muscle fibers expressed the lacZ gene 7 days after injection. The CAG promoter may have application in the development of gene therapy for Duchenne muscular dystrophy (DMD) using adenovirus vector.

Adenoviridae↗

Hypertension as a paraneoplastic syndrome in hepatocellular carcinoma.

We report a 66-year-old man with hepatocellular carcinoma who was positive for hepatitis B surface antigen, and was hospitalized because of hypoglycemia and hypertension. His plasma renin activity was normal (2.3 ng/ml per h), but concentrations of angiotensin I (>2500 pg/ml) and II (86 pg/ml) were high. Increased angiotensin I level at sites proximal and distal from the confluence of the hepatic vein and the inferior vena cava indicated that the hypertension was provoked by overproduction of angiotensin I from the hepatocellular carcinoma. Previous reports of patients with hepatocellular carcinoma with hypertension due to abnormality of renin-angiotensin system are reviewed.

Aged↗

Detection of bone invasion by gingival carcinoma of the mandible: a comparison of intraoral and panoramic radiography and computed tomography.

OBJECTIVE: To assess the diagnostic accuracy of panoramic radiography (PR), panoramic radiography combined with intraoral radiography (PR+IR), and CT in detecting the supero-inferior extent of tumor invasion of the mandible by gingival carcinoma. METHOD: PR, PR+IR, and CT images of the mandible in 37 patients with gingival carcinoma were evaluated by five oral radiologists for the supero-inferior extent of bone invasion using ROC analysis. The mean ROC curve area (Az) of each observer for the different imaging modalities was analysed by nonparametric two-way ANOVA. P<0.05 was considered statistically significant. RESULTS: The mean Az for the detection of bone invasion were 0.88+/-0.03 for PR, 0.77+/-0.12 for PR+IR, and 0.87+/-0.03 for CT (P=0.0907). The mean Az for the detection of bone invasion beyond the alveolus was 0.89+/-0.07 for PR, 0.85+/-0.08 for PR+IR, and 0.83+/-0.06 for CT (P=0.5438). The mean Az for the detection of bone invasion beneath the mandibular canal were 0.94+/-0.04 for PR, 0.94+/-0.02 for PR+IR, and 0.91+/-0. 04 for CT (P=0.2466). No statistically significant differences were observed in Az between PR, PR+IR, and CT. CONCLUSION: We consider that PR+IR should be adopted as the initial imaging modality to determine the extent of supero-inferior invasion of the mandible in gingival carcinoma.

Analysis of Variance↗

Nephrogenic adenoma of the bladder in a chronic hemodialysis patient.

BACKGROUND: Nephrogenic adenoma is an uncommon, benign metaplastic lesion occurring in the urothelium, usually as a response to chronic irritation or trauma. It is rarely encountered in hemodialysis patients. Endoscopically, these lesions can easily be mistaken for malignant tumors. METHODS/RESULTS: We report on a case of nephrogenic adenoma of the bladder in a chronic hemodialysis patient that was large and mistakenly diagnosed as transitional cell carcinoma in the initial biopsy. Histopathological examination of the total cystectomy specimen demonstrated the correct diagnosis of nephrogenic adenoma. CONCLUSION: Increased awareness by urologists and pathologists of nephrogenic adenoma may lead to its more accurate diagnosis.

Adenoma↗

Effective restoration of dystrophin-associated proteins in vivo by adenovirus-mediated transfer of truncated dystrophin cDNAs.

A series of truncated dystrophin cDNAs (3.1-4.2 kbp) containing only three, three, two or one rod repeats with hinge 1 and 4 (named deltaDysAX2, AX11, AH3, M3, respectively) or no rod repeat retaining either hinge 1 or 4 (named deltaDysH1, H4, respectively) were constructed. These cDNAs were introduced into skeletal muscle of adult mdx mice using the adenovirus vector with a strong CAG promoter. deltaDysAX2, AX11, AH3 and deltaDysM3 expressed themselves successfully and recovered dystrophin-associated proteins effectively. Especially 3.7 kbp cDNA for deltaDysM3 offers the possibility of an approach utilizing newly developed virus vectors, such as an adeno-associated virus vector, toward gene therapy of Duchenne muscular dystrophy.

Adenoviridae↗