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Biomedical subjects

Hideo Saito

Publications and source records attributed to Hideo Saito.

17 recordsLinked to original sources

Treatment of ruptured fusiform aneurysm in the posterior cerebral artery with posterior cerebral artery-superior cerebellar artery anastomosis combined with parent artery occlusion: case report.

BACKGROUND: Surgical management of a fusiform aneurysm in the PCA sometimes requires occlusion of the parent artery. In such cases, reconstruction of the PCA may prevent the development of postoperative visual field defects. CASE DESCRIPTION: A 30-year-old woman with a fusiform aneurysm in the P2 of the left PCA presented with subarachnoid hemorrhage. The left superficial temporal artery and OA were hypoplastic. Left temporal craniotomy revealed that the lateromesencephalic ambient segment of the SCA and the posterior half portion of the P2 segment ran parallel and near each other, and that the calibers of both arteries were relatively consistent. Thus, the 2 arteries were anastomosed in a side-to-side fashion, and the anterior half of the left P2 segment was occluded by clipping proximal and distal to the aneurysm that was located at the left P2 segment just distal to the junction to the posterior communicating artery. The patient had an uneventful postoperative course, and postoperative cerebral angiography demonstrated resolution of the aneurysm, with perfusion of the left PCA from the left SCA via the anastomosis. CONCLUSIONS: Posterior cerebral artery-superior cerebellar artery anastomosis is a useful method of achieving PCA reconstruction in the context of a PCA aneurysm requiring occlusion of the parent vessel and when superficial temporal artery or OA-PCA anastomosis cannot be performed.

Adult↗

[Significance of extracellular matrix determined by immunostains and histochemical stains in a case of pulmonary epithelioid hemangioendothelioma].

We have analyzed extracellular matrix(ECM) of a case of pulmonary epithelioid hemangioendothelioma (PEH). Type IV collagen and laminin were existed in the ECM and were condensed around the tumor cell nests in meshwork pattern. Elastica-van Gieson stain revealed elastic fibers in this meshwork. These findings suggested that enhanced basement membrane protein synthesis in PEH seems to be responsible for the accumulation of abundant ECM. Analysis of the ECM seems to be quite useful for the differential diagnosis of this tumor.

Adult↗

Post-laminectomy long-term survival of a patient with spinal cord compression secondary to metastatic prostate cancer.

Spinal cord compression is a skeletal-related event in advanced malignancies and is associated with serious morbidity and poor prognosis. Despite the palliative nature of laminectomy treatment, it is important to prevent neurological deficits and relieve pain as a means to improve quality of life. Here we report on a prostate cancer patient with spinal cord compression who became ambulant from paraparesis after he underwent a decompression laminectomy; he survived for 9.5 years with good quality of life.

Decompression, Surgical↗

Arbitrary viewpoint video synthesis from multiple uncalibrated cameras.

We propose a method for arbitrary view synthesis from uncalibrated multiple camera system, targeting large spaces such as soccer stadiums. In Projective Grid Space (PGS), which is a three-dimensional space defined by epipolar geometry between two basis cameras in the camera system, we reconstruct three-dimensional shape models from silhouette images. Using the three-dimensional shape models reconstructed in the PGS, we obtain a dense map of the point correspondence between reference images. The obtained correspondence can synthesize the image of arbitrary view between the reference images. We also propose a method for merging the synthesized images with the virtual background scene in the PGS. We apply the proposed methods to image sequences taken by a multiple camera system, which installed in a large concert hall. The synthesized image sequences of virtual camera have enough quality to demonstrate effectiveness of the proposed method.

Algorithms↗

Risk factors in past histories and familial episodes related to development of testicular germ cell tumor.

BACKGROUND: A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus. METHODS: The past health histories and familial episodes of 240 testicular germ cell tumor patients were examined. The past health histories included cryptorchism, hypospadias, infertility, atrophic testis and inguinal hernia. RESULTS: Of the 240 patients, 13 (5.4%) had a history of cryptorchism or orchidopexy. Two (0.8%) showed existence of hypospadias or had experienced urethroplasty. Among 129 married couples, 104 (80.6%) couples were fertile. Three (1.3%) patients developed testicular tumors after they were diagnosed as infertile or came to the hospital with the complaints of infertility. Four (1.7%) had contralateral atrophic testis. 19 (7.9%) had experienced inguinal herniorrhaphy before age 15. Three (1.3%) had testicular germ cell tumor patients among their family or relatives. CONCLUSIONS: The testicular germ cell tumor patients showed a considerable incidence of complications such as cryptorchism, hypospadias and incomplete closure of processus vaginalis. Cryptorchism, perinatal factors and familial factors could be risks for developing testicular germ cell tumors.

Adolescent↗

Clinical features of testicular tumors in children.

AIM: Testicular tumors are not common pediatric solid tumors, especially in Asian children. There have been few reviews of cases in Japan to date. We present the clinical features of 14 pediatric testicular tumor patients. METHODS: Clinical features of 14 testicular tumor patients, such as chief complaints, age at diagnosis, pathology, stages, treatments and prognosis, were examined from medical records. Two patients had their semen tested at adolescence. RESULTS: Of the 14 prepubescent patients, 12 (85.7%) patients were diagnosed before 3 years of age. Ten cases (71.4%) were diagnosed as yolk sac tumors, three (21.4%) as mature teratomas and one case as an epidermoid cyst. Nine cases (90.0%) among the 10 cases of yolk sac tumor were diagnosed as stage I and one case was stage IV. One stage I yolk sac tumor patient developed lung metastasis later. Eventually, two yolk sac tumor patients died, despite chemotherapy. While all the cases with a diagnosis before 2 years of age survived, 67% (2/3) of cases with a diagnosis after the age of 2 died of tumors. Semen analysis in two patients showed normospermia. CONCLUSION: In the present study, the most common testicular tumors were yolk sac tumors and the patients diagnosed before 2 years of age showed favorable results. Age could be a relapse risk factor in yolk sac tumors. Guidelines for handling testicular tumors in children is not yet well established in Japan. An organized system seems necessary to gather and accumulate the results of the cases in Japan in order to develop better guidelines for treatment.

Child↗

Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: identification of responders incorporating the age factor.

To identify responders when protein-bound polysaccharide (PSK) is used in adjuvant immunochemotherapy after curative resection of colorectal cancers, we examined the host and tumor factors that affect the prognosis incorporating the age factor. A total of 101 patients who had undergone macroscopic curative resection of colorectal cancer were treated with mitomycin C + fluoropyrimidine oral antineoplastics + PSK (MFP therapy) for two years in principle. These cases were divided into two age groups of <65 years [n=55; 54.8 +/- 8.3 years (mean +/- SD)] and > or =65 years (n=46; 69.1 +/- 3.3 years). Host factors including humoral factors (complement C3 and C4), immunosuppressive acidic protein (IAP), lymphocyte transformation (cellular factors) induced by various mitogens [phytohemagglutinin (PHA), pokeweed mitogen (PWM), and PSK], and tumor markers (CEA, CA19-9) were measured. The cases were divided by the cut-off value of each parameter into > or = cut-off value and < cut-off value groups, and the 5-year survival rates were compared. The cut-off values obtained for these parameters and the tumor factor (Dukes class) were subjected to multivariate analysis to identify the markers that affect prognosis. The 5-year mortality rate was 74.5% in the <65 age group and 56.8% in the > or =65 age group, with a tendency of better prognosis in the <65 age group (p=0.1109). Compared to the <65 age group, the > or =65 age group showed higher levels of C3 (2-way ANOVA: p=0.0582), C4 (p=0.0009) and IAP (p=0.0110) over time, but lower PSK-induced stimulation index (SI) as an indicator of cellular immunity) (p=0.0001) and PHA-induced SI (p=0.2650) over time. These results indicated that compared to patients aged <65 years, patients aged > or =65 years were characterized by lowered cellular immunity in addition to augmented complement production and an aggravated immunosuppressive state, suggesting the presence of some differences in host immune function with aging. Using the Cox proportional hazard model, the prognostic determinant was found to be Dukes C in the <65 age group, and CEA level in the > or =65 age group. The present results suggested that analysis of prognostic determinants of this therapy should take into account the age factor. Especially in elderly subjects, responders to PSK may be identified using the preoperative CEA value.

Adult↗

Gene transfer of alpha1,3-fucosyltransferase increases tumor growth of the PC-3 human prostate cancer cell line through enhanced adhesion to prostatic stromal cells.

Elevated expression of sialyl Lewis X has been postulated to be a prognostic indicator of prostate cancer. However, direct evidence for the relationship between increased expression of sialyl Lewis X and malignancy of prostate cancer is still lacking. To determine whether increased levels of sialyl Lewis X leads to malignancy in prostate tumor, we transfected the human prostate cancer cell line PC-3 with alpha1,3-fucosyltransferase III (FTIII) to obtain stable transfectants, PC-3-FTIII lines, that highly express sialyl Lewis X. When inoculated in the prostate of nude mice, PC-3-FTIII cells produced large prostate tumors, while mock-transfected PC-3 cells, which are negative for sialyl Lewis X antigen, produced small prostate tumors. The aggressive tumor formation by PC-3-FTIII cells was inhibited by preincubation of the tumor cells with anti-sialyl Lewis X antibody, by the presence of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide but not by control peptide. PC-3-FTIII cells and mock-transfected PC-3 cells exhibited no significant difference in cell numbers when cultured in vitro. Remarkably, PC-3-FTIII adhered to prostatic stromal cells in vitro with higher affinity than mock-transfected PC-3. Such adhesion was inhibited by preincubation of PC-3-FTIII cells with antisialyl Lewis X antibody, by the addition of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide. However, anti-E-selectin, anti-P-selectin or anti-L-selectin antibodies did not inhibit the adhesion of PC-3-FTIII cells to the stromal cells. These results suggest that prostate cancer cells gain aggressiveness through adhesive interaction with prostatic stromal cells by a novel mechanism involving sialyl Lewis X.

Adenocarcinoma↗

Tocolytic effects of formoterol are associated with local change in the progesterone/estradiol ratio.

OBJECTIVE: The aim of the study was to determine whether a beta(2)-adrenoceptor agonist, formoterol, inhibits premature delivery in connection with change in estradiol and progesterone concentrations in the amniotic fluid in ovariectomized rats. STUDY DESIGN: Pregnant rats at the 15th day of gestation were bilaterally ovariectomized and given injection of 17beta-estradiol immediately after the operation and every 24 h. An osmotic pump filled with a solution of formoterol or saline was also implanted subcutaneously into the back of each. The animals were killed by decapitation under light ether anesthesia 18, 36, 54 or 72 h after ovariectomy, and the numbers of undelivered fetuses and newborn were counted. Amniotic fluid was collected 16, 36, and 54 h after ovariectomy. RESULTS: Formoterol (0.15 mg/(kg h)) reversed the decline in premature delivered fetuses due to 17beta-estradiol 54 and 72 h after ovariectomy. Although no influence was evident regarding the progesterone and estradiol concentrations in amniotic fluid in ovariectomized rats supplemented with 17beta-estradiol, formoterol significantly inhibited the increment in the estradiol/progesterone ratio as well as the elevation in prostaglandin F2alpha concentration. CONCLUSION: These findings indicate that tocolytic effects of formoterol may be associated with suppression of uterine activity due to modulation of hormone secretion.

Adrenergic beta-Agonists↗

OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium.

Otx2 is a member of homeodomain-containing transcription factors and is essential for eye morphogenesis in mice. Here we show the expression of OTX2, the human counterpart of Otx2, in cell lines of retinal pigment epithelium (RPE) and in Y79 retinoblastoma cells that exhibit the property of presumptive RPE. These RPE cells express DOPAchrome tautomerase (DCT) that is an enzyme involved in melanin biosynthesis. DCT may contribute to the homeostasis of RPE by detoxifying DOPA-derived metabolites. OTX2 binds to the DCT gene promoter in vivo, as judged by chromatin immunoprecipitation assays. Furthermore, repression of endogenous OTX2 expression in Y79 cells by an anti-sense OTX2 oligonucleotide resulted in the decrease of DCT protein contents. Transient expression assays revealed that OTX2 activated the DCT gene promoter through the OTX-2-binding site in an RPE-specific manner. Therefore, OTX2 may regulate RPE-specific target genes, such as DCT, thereby maintaining the homeostasis of RPE.

Adolescent↗

Microphthalmia-associated transcription factor in the Wnt signaling pathway.

Microphthalmia-associated transcription factor (MITF) contains a basic helix-loop-helix and leucine-zipper (bHLH-LZ) structure and consists of many isoforms with different N-termini. Melanocyte-specific MITF isoform (MITF-M) is of particular interest, because a heterozygous mutation in the MITF gene is associated with Waardenburg syndrome type 2 (WS2) that is characterized by deafness and hypopigmentation because of lack of melanocytes in the inner ear and skin. Expression of MITF-M is under the regulation of the melanocyte-specific promoter (M promoter) of the MITF gene, and transcription from the M promoter is induced by Wnt signals through a nuclear mediator, lymphoid-enhancing factor 1 (LEF-1). In addition, functional cooperation of MITF-M with LEF-1 could lead to transcriptional activation of the M promoter and the dopachrome tautomerase (DCT) gene, an early melanoblast marker. The bHLH-LZ region of MITF-M is responsible for the physical interaction with LEF-1, and beta-catenin is required for the collaboration between LEF-1 and MITF-M. Importantly, MITF-M could function as a non-DNA-binding co-factor for LEF-1. These results suggest that MITF-M may function as a self-regulator of its own expression to maintain a threshold level of MITF-M at a certain sensitive stage of melanocyte development, which could account for the dominant inheritance of WS2. MITF-M therefore plays dual roles in the Wnt signaling pathway; MITF-M represents a downstream target and a nuclear mediator of Wnt signals in melanocytes.

Animals↗

Germ cell-specific expression of microphthalmia-associated transcription factor mRNA in mouse testis.

The gene coding for microphthalmia-associated transcription factor (Mitf) contains many promoters that could generate multiple Mitf isoforms with distinct amino-termini, such as ubiquitously expressed Mitf-A and Mitf-H. To gain further insight into Mitf isoform multiplicity and the regulation of the promoter usage of the Mitf gene, we have analyzed the function of the amino-terminal domains of Mitf isoforms and the expression of Mitf mRNA in mouse postnatal testis, which is characterized by spermatogenesis and by a cool temperature because of its unique location. Here we show that the amino-terminal domain of Mitf-A possesses a transactivation activity, as judged by yeast expression analysis. We also show the expression of Mitf-A and Mitf-D mRNAs in testis by PCR-based methods. Moreover, in situ hybridization analysis revealed that an Mitf mRNA, probably representing Mitf-A and/or Mitf-D, is expressed in germ cells, including spermatogonia, spermatocytes that undergo meiosis, and round spermatids with the haploid genome, but is undetectable in elongated spermatids with remodeled and condensed chromatin. Notably, Mitf mRNA is undetectable in somatic Leydig cells and peritubular cells. Therefore, multiple promoters may direct differential expression of the Mitf gene in the testis and contribute to functional diversity of Mitf isoforms.

Animals↗

Melanocyte-specific microphthalmia-associated transcription factor isoform activates its own gene promoter through physical interaction with lymphoid-enhancing factor 1.

Waardenburg syndrome type 2 (WS2) is associated with heterozygous mutations in the gene encoding microphthalmia-associated transcription factor (MITF) and characterized by deafness and hypopigmentation due to lack of melanocytes in the inner ear and skin. Melanocyte-specific MITF isoform (MITF-M) is essential for melanocyte differentiation and is transcriptionally induced by Wnt signaling that is mediated by beta-catenin and LEF-1. Here we show that MITF-M transactivates its own promoter (M promoter) by interacting with LEF-1, as judged by transient expression assays and in vitro protein-protein binding assays, whereas no transactivation of the M promoter was detected with MITF-M alone or with the combination of MITF-M and dominant-negative LEF1 that lacks the beta-catenin-binding domain. This synergy depends on the three LEF-1-binding sites that are clustered in the proximal M promoter. Importantly, MITF-M recruited on the M promoter could function as a non-DNA-binding cofactor for LEF-1. Thus, MITF-M may function as a self-regulator of its own expression to maintain a threshold level of MITF-M that is required for melanocyte development. We suggest that MITF-M haploinsufficiency may impair the dosage-sensitive role of MITF-M or the correct assembly of multiple transcription factors, involving MITF-M, on the M promoter, which could account for dominant inheritance of WS2.

Animals↗

Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling.

Wnt signals regulate differentiation of neural crest cells through the beta-catenin associated with a nuclear mediator of the lymphoid-enhancing factor 1 (LEF-1)/T-cell factors (TCFs) family. Here we show the interaction between the basic helix-loop-helix and leucine-zipper region of microphthalmia-associated transcription factor (MITF) and LEF-1. MITF is essential for melanocyte differentiation and its heterozygous mutations cause auditory-pigmentary syndromes. Functional cooperation of MITF with LEF-1 results in synergistic transactivation of the dopachrome tautomerase (DCT) gene promoter, an early melanoblast marker. This activation depends on the separate cis-acting elements, which are also responsible for the induction of the DCT promoter by lithium chloride that mimics Wnt signaling. beta-catenin is required for efficient transactivation, but dispensable for the interaction between MITF and LEF-1. The interaction with MITF is unique to LEF-1 and not detectable with TCF-1. LEF-1 also cooperates with the MITF-related proteins, such as TFE3, to transactivate the DCT promoter. This study therefore suggests that the MITF/TFE3 family is a new class of nuclear modulators for LEF-1, which may ensure efficient propagation of Wnt signals in many types of cells.

Amino Acid Sequence↗

Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations.

Microphthalmia-associated transcription factor (Mitf) regulates the differentiation of melanocytes, optic cup-derived retinal pigment epithelium (RPE), and some types of bone marrow-derived cells. Mitf consists of at least five isoforms with different N-termini, each of which is encoded by a separate exon 1. Here we identified a novel isoform, termed mouse Mitf-D/human MITF-D, that is expressed in RPE, macrophages, and osteoclasts affected by the Mitf mutations, but not expressed in other Mitf target cells, including melanocyte-lineage cells and natural killer cells. The initiation Met of MITF-D is located in the downstream domain (B1b domain) that is shared by other MITF isoforms. The 5'-untranslated region of MITF-D mRNA is encoded by the newly identified first exon of the MITF gene, termed exon 1D, which is located 3 kb upstream of the exon encoding the B1b domain. Thus, the MITF gene generates multiple isoforms with different expression patterns by using the alternative promoters in a cell-dependent manner, thereby providing the molecular basis for the phenotypic variability seen in the MITF/Mitf mutants.

Adolescent↗

Identification of a distal enhancer for the melanocyte-specific promoter of the MITF gene.

Waardenburg syndrome (WS) is characterized by deafness and hypopigmentation because of the lack of melanocytes in the inner ear and skin. WS type 2 is associated with mutations in the gene encoding microphthalmia-associated transcription factor (MITF) that is required for melanocyte differentiation. MITF consists of multiple isoforms with different N-termini, one of which is exclusively expressed in melanocytes, named MITF-M. Its N-terminus is encoded by exon 1M that is under the regulation of the melanocyte-specific (M) promoter. Here we identify a distal regulatory region of 298 bp, located 14.5 kb upstream from exon 1M, which enhances the M promoter activity in cultured melanoma cells. This enhancer activity depends on the proximal M promoter region (-120 to -46). The MITF-M distal enhancer (MDE), thus identified, contains the binding sites for SOX10, a transcription factor responsible for another type of WS, known as Waardenburg-Hirschsprung syndrome. Characterization of MDE has suggested SOX10 as one of factors that are involved in the function of MDE. A putative MDE counterpart is located 12 kb upstream from mouse exon 1M and its role is discussed in relevance to the pathogenesis of red-eyed white Mitf mi-rw mice that exhibit small red eyes and white coat. Moreover, by in situ hybridization analysis, we suggest that Sox10 and Mitf-M (mRNA) are expressed in melanoblasts migrating toward the otic vesicle (prospective inner ear) of mouse embryos but are separately expressed in different cell types of the newborn cochlea. Thus, SOX10 regulates transcription from the M promoter in a developmental stage-specific manner.

Animals↗

Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: Association between host or tumor factors and survival.

We examined the relationship between host as well as tumor factors and postoperative survival rate in patients who received combination therapy of mitomycin C + fluoropyrimidine oral antineoplastics + protein-bound polysaccharide K (PSK) (MFP therapy) after curative resection of colorectal cancer. Markers that determine prognosis, such as preoperative humoral factors (complement 3 and 4), immunosuppressive acidic protein (IAP), lymphocyte transformation (cellular factors) induced by phytohemagglutinin (PHA), pokeweed mitogen (PWM), and PSK, and various tumor markers (CEA, CA19-9) were measured. For each parameter, patients were divided into a high-level and a low-level group according to a predetermined cut-off value, and survival rates were compared between the two groups. The host factors that determined prognosis were 1-month postoperative IAP level [IAP(1M)], preoperative PHA value, and preoperative CA19-9 level. The levels of IAP(1M) <740 microg/ml, preoperative PHA > or =210 (SI value), and preoperative CA19-9 <13 U/ml were associated with a favorable prognosis. When combined with the tumor factors, the prognosis was favorable in Dukes A+B cases with preoperative CA19-9 <13 U/ml, and in Dukes C cases with preoperative PHA > or =210 SI. By the Cox proportional hazard model analysis, among IAP, PHA and CA19-9, CA19-9 was the strongest host factor associated with the prognosis of MFP therapy.

Aged↗