Biomedical subjects

Haruo Saito

Publications and source records attributed to Haruo Saito.

At least 19 recordsLinked to original sources

PubMed2006

Types and frequencies of biliary tract variations associated with a major portal venous anomaly: analysis with multi-detector row CT cholangiography.

PURPOSE: To retrospectively determine whether major portal venous variation was more frequently associated with biliary variants, with consideration of the types and frequencies of biliary tract variations in the right and left liver lobes. MATERIALS AND METHODS: Before undergoing computed tomographic (CT) cholangiography, patients gave informed consent. The retrospective research protocol was approved, and informed consent was waived by the ethics committee. Forty-four patients aged 29-80 years who underwent multi-detector row CT cholangiography had a major portal vein variation in which the main portal vein diverged into the common trunk of the left portal vein and right anterior sectorial portal vein. One hundred fifty-eight consecutive patients aged 26-89 years who did not have this variation served as the control group. Three radiologists retrospectively evaluated the confluence pattern of the bile duct, the relationship between this pattern and the portal vein, and the major branching pattern of the portal vein. Pearson chi2 and Fisher exact tests were performed to identify significant differences between the two patient groups. RESULTS: The classic hilar confluence pattern, where the right posterior sectorial duct connects supraportally with the right anterior sectorial duct, was less frequent in the patients with the portal vein variation than in the control subjects (32% vs 73%, P < .05). The following biliary tract variations were identified more frequently in the variation group than in the control group (P < .05): right posterior sectorial duct joining left hepatic duct with a supraportal course (34% vs 12%), right posterior sectorial duct joining right anterior sectorial duct with an infraportal course (13% vs 4%), right posterior sectorial duct following an infraportal course (23% vs 8%), and left lateral segmental ducts caudal to the umbilical portion of the portal vein (14% vs 3%). The right hepatic duct, which receives all biliary ducts from the right lobe, was significantly less frequently developed in the variation group (46% vs 79%, P < .05). In addition, retroportal bile ducts were seen in four patients with the portal vein variation (P < .05). CONCLUSION: Bile duct configurations in patients with portal vein variation were significantly different from those in control subjects.

Adult↗

PubMed2005

Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity.

Several new phorbol derivatives having ethereal substituents at the 12-position were synthesized and subjected to biological evaluation to find new candidates of an anti-HIV agent. Among them, 12-O-(methoxymethyl)phorbol 13-decanoate showed potent inhibitory activity against infection of HIV-1 in MT-4 cells (EC50: 1.3 ng/mL) and relatively low cytotoxicity (CC50: 8.3 microg/mL). This compound was also found to have sufficient stability in mouse plasma compared with the corresponding 12-acetate derivative, which was an equipotent HIV-1 inhibitor, but with an activity that decreased considerably after plasma treatment.

Anti-HIV Agents↗

PubMed2005

Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy.

PURPOSE: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. METHODS AND MATERIALS: We examined 35 patients with non-small-cell lung cancer (n = 27, 77%) and small-cell lung cancer (n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50-83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. A median dose of 60 Gy (range, 50-67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9-67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. RESULTS: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage of esophageal volume receiving >35 Gy on univariate (p = 0.002) and multivariate (p = 0.018) analyses. CONCLUSION: The percentage of esophageal volume receiving >35 Gy was the most statistically significant factor associated with mild acute esophagitis.

Acute Disease↗

PubMed2005

Edema in the retropharyngeal space associated with head and neck tumors: CT imaging characteristics.

To determine computed tomographic (CT) imaging characteristics of retropharygeal edema, we reviewed CT images in 18 patients with head and neck tumors. Retropharyngeal edema spread craniocaudally between soft palate and upper half of thyroid cartilage in all patients. No edema fluid extended above soft palate and below thyroid cartilage. Horizontally, it spread symmetrically in ten and asymmetrically in eight patients. Predominance in asymmetrical retropharyngeal edema was found on the same side as that of unilateral predominance both in lymph nodes enlargement and jugular vein stenosis/occlusion. All patients had edema also in other cervical spaces. Edema of retropharyngeal and other spaces fluctuated synchronously. In 14 patients, as primary lesion and/or cervical lymph nodes regressed, retropharyngeal edema disappeared or decreased. Retropharyngeal edema had some imaging characteristics. With knowledge of that, we could avoid diagnostic confusion when evaluating head and neck CT images.

Adult↗

PubMed2005

Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases.

Mammalian mitogen-activated protein kinase (MAPK) cascades control various cellular events, ranging from cell growth to apoptosis, in response to external stimuli. A conserved docking site, termed DVD, is found in the mammalian MAP kinase kinases (MAPKKs) belonging to the three major subfamilies, namely MEK1, MKK4/7, and MKK3/6. The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAPKKKs), including MTK1 (MEKK4), ASK1, TAK1, TAO2, MEKK1, and Raf-1. DVD site is a stretch of about 20 amino acids immediately on the C-terminal side of the MAPKK catalytic domain. Mutations in the DVD site strongly inhibited MAPKKs from binding to, and being activated by, their specific MAPKKKs, both in vitro and in vivo. DVD site mutants could not be activated by various external stimuli in vivo. Synthetic DVD oligopeptides inhibited specific MAPKK activation, both in vitro and in vivo, demonstrating the critical importance of the DVD docking in MAPK signaling.

Amino Acid Sequence↗

PubMed2005

Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45.

CD45 is the prototypic member of transmembrane receptor-like protein tyrosine phosphatases (RPTPs) and has essential roles in immune functions. The cytoplasmic region of CD45, like many other RPTPs, contains two homologous protein tyrosine phosphatase domains, active domain 1 (D1) and catalytically impaired domain 2 (D2). Here, we report crystal structure of the cytoplasmic D1D2 segment of human CD45 in native and phosphotyrosyl peptide-bound forms. The tertiary structures of D1 and D2 are very similar, but doubly phosphorylated CD3zeta immunoreceptor tyrosine-based activation motif peptide binds only the D1 active site. The D2 "active site" deviates from the other active sites significantly to the extent that excludes any possibility of catalytic activity. The relative orientation of D1 and D2 is very similar to that observed in leukocyte common antigen-related protein with both active sites in an open conformation and is restrained through an extensive network of hydrophobic interactions, hydrogen bonds, and salt bridges. This crystal structure is incompatible with the wedge model previously suggested for CD45 regulation.

Amino Acid Sequence↗

PubMed2005

Heterogeneity of subvesical ducts or the ducts of Luschka: a study using drip-infusion cholangiography-computed tomography in patients and cadaver specimens.

The objective of this study was to examine the heterogeneity of the subvesical duct or the ducts of Luschka as well as the reliability of drip-infusion cholangiography with computed tomography (DIC-CT) for their identification. DIC-CT was used in 277 consecutive patients (135 men, 142 women) and for the dissection and histologic study of 10 cadaver livers. We found 32 subvesical ducts in 28 (10.1%) of 277 patients. Irrespective of whether the terminals were extra- or intraparenchymal, the subvesical ducts often (17/32 ducts, 15/28 patients) drained into a subsegmental duct of S5 or S4. Notably, some displayed an "intermediate" course along the gallbladder fossa with an intraparenchymal origin and terminated at S5. Such ducts tended to be seen in the elderly. Another 15 ducts drained into a thick, centrally located duct, such as the right sectorial or hepatic duct. The anatomic study demonstrated that the subvesical duct likely included the cystic vein-concomitant duct. A major type of subvesical duct, characterized by an intermediate course along its bed, appeared to result from degenerative exposure of a peripheral duct with aging. The subvesical duct draining into the thick duct included both a "daughter branch," such as seen in the lung, and the so-called anomaly. Such ducts can be demonstrated with DIC-CT, but the incidence might be limited. However, the cystic vein/concomitant duct was difficult to identify radiologically. Consequently, although presurgical radiology is useful for avoiding bile leakage after laparoscopic cholecystectomy, surgeons should be aware of its limitations.

Adolescent↗

PubMed2005

Time-related changes in computed tomographic appearance and pathologic findings after radiofrequency ablation of the rabbit lung: preliminary experimental study.

PURPOSE: To evaluate correlations between computed tomographic (CT) appearance and pathologic findings after radiofrequency (RF) ablation of lungs and to determine whether CT appearance could predict the extent of the effective therapeutic area. MATERIALS AND METHODS: The lungs of 14 rabbits were subjected to RF ablation and CT scans were obtained immediately and at various intervals thereafter. Four rabbits were killed immediately after the initial CT imaging (n = 4). The remaining 10 rabbits were killed after additional CT scans at intervals of 3 days (n = 2), 1 week (n = 4), 2 weeks (n = 2), and 3 weeks (n = 2) after RF ablation. Pathologic findings were correlated with CT appearance. RESULTS: Immediately after RF ablation, a restricted area of central dense opacity enclosed by an extensive area of ground-glass opacity was noted in the ablated region on CT images. Pathologically, the former corresponded to destructive tissue and the latter corresponded to tissue with some degree of injury. After 1 week, the entire ablated region appeared as a well-demarcated homogeneous dense opacity on CT that corresponded to necrotic tissue and its surrounding rim of granulation tissue on histopathologic examination, indicating that the enclosing extensive area of ground-glass opacity on the initial CT scan represented an ongoing necrosis. Within 2-3 weeks, the ablated region gradually contracted on the CT images, representing a tissue repairing process in which the granulation tissue was encroaching on the inner necrotic tissue. CONCLUSION: Ground-glass opacity of the ablated region on CT immediately after RF ablation represents an ongoing necrosis.

Animals↗

PubMed2005

Novel phorbol esters exert dichotomous effects on inhibition of HIV-1 infection and activation of latent HIV-1 expression.

Two new phorbol esters, NPB-11 (12-O-methoxymethylphorbol-13-decanoate) and NPB-15 (12-O-benzyloxymethylphorbol-13-decanoate) were synthesized. The compounds exhibited potent anti-HIV-1 activity and low cytotoxicity in MT-4 cells by MTT assay even at a high concentration [50% cytotoxic concentrations (CC50) were 8.32 and 4.39 microg/ml, respectively]. Two inhibitors strongly suppressed HIV-1 (IIIB strain) replication in MT-4 cells with a 50% effective concentration (EC50) of 1.3 and 0.27 ng/ml, respectively. NPB-11 efficiently blocked replication of both X4 and R5 HIV-1 in PHA-activated peripheral blood mononuclear cells and MT-4 cells as revealed by p24 assay. The antiviral activity appeared to be mediated, at least partially, by the down-regulation of the expression of CD4 and the HIV-1 co-receptors, CXCR4 and CCR5. The compounds were also capable of selectively up-regulating HIV-1 expression in a variety of latently infected cell lines and inducing cell death in HIV-1 infected cells. The effect of NPBs on the induction of HIV-1 was specifically blocked by nontoxic doses of a protein kinase C blocker, staurosporine. NPB-11 blocked the spread of HIV-1 released from latently infected ACH-2 cells to MT-4 cells in a co-culture system. When combined with AZT, NPB-11 synergistically inhibited HIV-1 replication in MTT assay using MT-4 cells. These data suggest that these agents might be useful in reducing persistent viral reservoirs in patients and as adjuvant therapy in patients treated with HAART.

Anti-HIV Agents↗

PubMed2005

Antioxidant and antiviral activities of plastoquinones from the brown alga Sargassum micracanthum, and a new chromene derivative converted from the plastoquinones.

Two plastoquinones were isolated from the methanolic extract of the brown alga Sargassum micracanthum, and these were identified as a known 2-geranylgeranyl-6-methylbenzoquinone and its hydroquinone, respectively, based on spectroscopic analysis. The absolute configuration of the secondary hydroxyl group was determined by the modified Mosher's method using the new chromene derivative converted from plastoquinones. One of the plastoquinones and the chromene exhibited significant antioxidant activities, such as an inhibitory effect on lipid peroxidation and a radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH). The benzoquinone-type compound and the chromene derivative were found to have potent antiviral activity against human cytomegalovirus (HCMV).

Animals↗

PubMed2005

New plastoquinones isolated from the brown alga, Sargassum micracanthum.

Four new plastoquinones were isolated from the methanolic extract of the brown alga, Sargassum micracanthum. Their structures were elucidated based on spectroscopic analysis and chemical conversions from 2-geranylgeranyl-6-methyl-1,4-benzohydroquinone. These plastoquinones exhibited significant antioxidant activities such as an inhibitory effect on lipid peroxidation and a radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH). Some of the new plastoquiones showed cytotoxic activity against cancer cell line.

Animals↗

PubMed2005

3beta-Hydroxysteroid dehydrogenase in human aorta.

3beta-Hydroxysteroid dehydrogenase (3beta-HSD) is known to be involved in steroid production and/or metabolism and to be expressed in many tissues including adrenal cortex. Expression of this enzyme has also been elucidated in human cardiovascular system but its details remain largely unknown. Therefore, in this study, we examined the status of 3beta-HSD in postmortem human aorta utilizing RT-PCR and immunohistochemical analysis. Both mRNAs and immunoreactivity for the enzyme were detected predominantly in female aorta, and in those with mild atherosclerotic changes. In addition, immunohistochemical study demonstrated that immunoreactivity for 3beta-HSD was detected in vascular smooth muscle cells (VSMCs) of aorta. These findings all indicated that steroidogenesis via 3beta-HSD may occur in VSMCs of human aorta, possibly related to gender differences and/or the degree of atherosclerosis.

3-Hydroxysteroid Dehydrogenases↗

PubMed2005

Progesterone receptor subtypes in vascular smooth muscle cells of human aorta.

Progesterone is involved in various functions of the cardiovascular system, including those of vascular smooth muscle cells (VSMCs) via progesterone receptor (PR). Progesterone has also been postulated to be involved in inhibition of VSMC proliferation via PR. However, the details of PR expression have remained largely unknown in human cardiovascular VSMCs. Therefore, we first examined the relative levels of PR isoform (PR-A and PR-B) expression in VSMCs, using both immunohistochemistry and quantitative RT-PCR analysis. PR-B was equally expressed between male and female aorta, but PR-A was more abundant in female than in male aorta. This finding demonstrated that the status of PR subtype expression was associated with the difference of genders.

Adult↗

PubMed2004

Spiegel's lobe bile ducts often drain into the right hepatic duct or its branches: study using drip-infusion cholangiography-computed tomography in 179 consecutive patients.

Using drip-infusion cholangiography-computed tomography (DIC-CT), we successfully identified the bile ducts draining the caudate lobe in 138 of 179 consecutive patients with extrahepatic cholelithiasis (179 ducts from Spiegel's lobe and 154 from the paracaval portion; 1-5 ducts per patient). The dorsal subsegmental duct of S8 (B8c) was often identified and could be discriminated from the paracaval caudate ducts, thus acting as a landmark for the right margin of the caudate lobe. Notably, in more than one-third of the 138 patients, at least one of the Spiegel's lobe ducts drained into the right hepatic duct or its branches (30.2% of the 179 ducts overall; all ducts joined branches of the right lobe in 25 patients). Similarly, 34.4% of the 154 paracaval caudate lobe ducts drained into the left hepatic duct or its branches. These "anatomical left/right dissociations" between the drainage territory and route were much more frequent than previously reported. Our results confirm the effectiveness of DIC-CT as a classical, noninvasive method for presurgical evaluation of the biliary system, but they also suggest that anatomical partial resection of the dorsal liver in patients with hilar cholangioma is often impossible because of contralateral biliary drainage.

Adolescent↗

PubMed2004

Pseudoaneurysm of the inferior epigastric artery successfully treated by ultrasound-guided compression.

An 82-year-old woman underwent right hemicolectomy by median laparotomy. Two weeks later, a pulsatile mass was found at the left side of the surgical wound, which was diagnosed as pseudoaneurysm of the inferior epigastric artery by color Doppler US and CT. The pseudoaneurysm was successfully treated by US-guided compression of the neck of the aneurysm for 30 minutes. US-guided compression should be considered the treatment of choice for postsurgical pseudoaneurysm of the inferior epigastric artery.

Aged↗

PubMed2004

Estrogen receptors in atherosclerotic human aorta: inhibition of human vascular smooth muscle cell proliferation by estrogens.

Estrogen has been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors (ERs) in vascular smooth muscle cells (VSMCs). Therefore, we believe it is important to examine the status of ER expression in the human cardiovascular system and its disorders. In this study, we first evaluated the relative abundance of messenger RNA (mRNA) of both ER subtypes (ERalpha and ERbeta) in the human aorta using reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR). We then examined the immunolocalization of both ERs in VSMCs of human atherosclerotic lesions. In order to examine which ER subtype was associated with the anti-atherogenic effects of estrogen, we examined the effects of estrogen in two VSMC cell lines, one positive only for ERalpha and the other positive only for ERbeta. The relative abundance of mRNAs for both ERs was higher in female aorta with a mild degree of atherosclerosis than in female aorta with a severe degree of atherosclerosis (P < 0.05). In addition, the number of ERalpha and/or ERbeta double positive cells in the neointima was higher in female aorta with a mild degree of atherosclerosis than in female aorta with severe atherosclerosis (P < 0.05). Our in vitro study found that estradiol was able to significantly inhibit the proliferation of ERalpha positive VSMCs but not ERbeta positive VSMCs (P < 0.05). Moreover, estradiol was found to significantly suppress proliferating cell nuclear antigen (PCNA) mRNA levels in ERalpha positive VSMCs compared to that of ERbeta positive VSMCs, consistent with the findings of cell proliferation. Results from this study suggest that estrogens can inhibit the proliferation of VSMCs through ERalpha, especially in pre-menopausal women. Our study also indicates that decreased levels of ER, especially ERalpha, in the female atherosclerotic neointima may be associated with progression of atherosclerotic changes.

Actins↗

PubMed2004

Low-dose CT of the thorax in cancer follow-up.

PURPOSE: To evaluate the quality of low-dose computed tomography (CT) images in the follow-up of cancer patients. MATERIALS AND METHODS: We selected patients with urogenital (n = 7) or esophageal cancer (n = 13) who were attending routine follow-up between April and July 2001. After water and chest phantom studies to decide the scan parameters, postcontrast low-dose CT scans were obtained at 60 mA (45 mA s) with a smoothing kernel. Three radiologists reviewed the CT scans of the thorax independently for overall image quality and anatomic detail in both mediastinal and lung windows. They subjectively rated the images on a four-point scale (0: poor, 1: fair, 2: good, 3: excellent) according to graininess and sharpness. RESULTS: The average score of the low-dose CT for the lung window was 2.85, which was equivalent to control images. The average score for the mediastinal window was 1.77, which was lower than that of the control CT scan (2.62, P < 0.001) and almost identical to that of the chest phantom experiment. Nine of the 20 cases had abnormal findings; low-dose CT scans depicted them well and offered sufficient information for diagnosis. The radiation exposure was reduced by about half. CONCLUSION: The image quality of low-dose thoracic CT was satisfactory for both mediastinal and lung windows in the follow-up of cancer patients.

Aged↗

PubMed2004

E4F1, a novel estrogen-responsive gene in possible atheroprotection, revealed by microarray analysis.

Estrogen has been postulated to be involved in inhibition of vascular smooth muscle cell (VSMC) proliferation mainly via estrogen receptor (ER), but the detailed mechanism has remained primarily unknown. Therefore, in this study, microarray analysis was used in two types of cultured human VSMCs: one positive for ER alpha, and the other for ER beta, which were treated by estrogens to detect the estrogen-responsive genes. We also used quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate mRNA levels of selective target gene (TG) in these cells. We further studied whether the TG product was involved in inhibition of proliferation using small interfering RNA (siRNA) of the TG transfection. We subsequently used quantitative RT-PCR and in situ hybridization analysis to evaluate the expression of these gene products in human aorta. E4F1, a possible inducer of cell growth arrest, was markedly increased only in ER alpha-positive VSMCs by estrogens in both microarray and RT-PCR analyses. Blocking of E4F1 using siRNA suppressed estrogenic inhibition of ER alpha-positive VSMC proliferation. E4F1 mRNA was abundant in premenopausal female aorta with mild atherosclerotic changes. E4F1 is therefore considered one of the estrogen-responsive genes involving ER alpha-mediated inhibition of VSMC proliferation and may play an important role in estrogen-related atheroprotection of human aorta.

Adenovirus E4 Proteins↗