Biomedical subjects

H Sakai

Publications and source records attributed to H Sakai.

At least 91 records · Page 5Linked to original sources

PubMed2001

A phase II study of paclitaxel plus cisplatin for advanced non-small-cell lung cancer in Japanese patients.

We performed a clinical phase II trial of the combination of paclitaxel and cisplatin in patients with locally advanced (stage IIIB) or metastatic non-small-cell lung cancer (NSCLC) using a 3-h infusion of paclitaxel followed by a 1 to 2-h infusion of cisplatin, with a short premedication regimen. Treatment was repeated every 21 days for at least two cycles. The patients received paclitaxel 180 mg/m2 followed by cisplatin 80 mg/m2. Enrolled in the trial were 33 chemotherapy-naive patients with stage IIIB (15%) or stage IV (85%) NSCLC. Their median age was 61 years (range 43-71 years). Of the 33 patients, 10 (30%) were women and 23 (70%) were men, and 82% had adenocarcinoma. With 78 courses of chemotherapy administered, 32 patients were evaluable for toxicity and response. Hematologic toxicities were moderate: Japan Clinical Oncology Group (JCOG) grade 3 or 4 neutropenia occurred in 37% of the cycles (53% of patients). Other toxicities consisted mainly of grade 1 or 2 alopecia and nausea/vomiting, but also included grade 1 or 2 neuropathy (47%), hypotension (grade 1 in 6%, grade 3 in 3%) and allergic reactions (grade 1 or 2 in 16%, grade 3 in 3%). Of 32 patients evaluable for response, a partial response was achieved in 10 (31%; 95% confidence interval 16% to 50%), stable disease was seen in 16 (50%), and disease progression was seen in 2 (6%). The median survival time was 14.8 months and the 1-year survival rate was 56%. These results suggest that the combination of paclitaxel and cisplatin is a well-tolerated and active regimen in Japanese patients with advanced NSCLC. In view of the promising survival outcomes, further evaluation in prospective randomized trials with other regimens is warranted.

Adult↗

PubMed2001

Expression of cadherins and their undercoat proteins (alpha-, beta-, and gamma-catenins and p120) and accumulation of beta-catenin with no gene mutations in synovial sarcoma.

E-cadherin, the major intercellular adhesion molecule of epithelial cells, is important in determining the architecture of sarcomas, especially those showing epithelioid features. In addition to its role in cell adhesion, beta-catenin, a cadherin undercoat protein, has been shown to function as a downstream transcriptional activator of the Wnt/Wingless signaling pathway. In order to evaluate the significance of the cadherin cell adhesion system and the Wnt/Wingless signaling pathway in the morphogenesis and/or tumorigenesis of synovial sarcoma (a major type of sarcoma with epithelioid features), immunoreactivity for pan-cadherin, E-cadherin, and their undercoat proteins (alpha-, beta-,and gamma-catenins and p120) was evaluated in 15 synovial sarcomas. Immunoreactivity for pan-cadherin, E-cadherin, alpha-catenin, beta-catenin, and p120 was observed in all 15 specimens. Immunoreactivity for pan-cadherin was stronger than that for E-cadherin. Expression of gamma-catenin was detected in ten specimens. Although beta-catenin was observed only at the cell-cell boundaries in four specimens, it was present in the nucleus and cytoplasm and at the cell-cell boundaries in the other 11, suggesting constitutional activation of the Wnt/Wingless signaling pathway in synovial sarcoma. Direct sequencing for exon 3 of the beta-catenin gene, however, revealed no mutations in any of the 15 specimens. In conclusion, other types of cadherin besides E-cadherin, together with cadherin undercoat proteins, may play a role in cell adhesion in synovial sarcoma. Furthermore, mechanisms other than mutation of exon 3 of the beta-catenin gene may activate the Wnt/Wingless signaling pathway in this type of tumor.

Adolescent↗

PubMed2001

Spontaneous total thrombosis of distal superior cerebellar artery aneurysm.

We report the case of an aneurysm of the distal segment of the superior cerebellar artery (SCA) which showed complete spontaneous thrombosis. Initial angiography performed in another institution showed 3 non-ruptured aneurysms located on the right distal SCA, C3 segment of the right internal carotid artery (ICA) and left basilar artery (BA)-SCA bifurcation. The patient had two episodes of transient cerebellar ataxia of the right hand before admission to our hospital, but no neurological signs were noted on admission. Computed tomography (CT) and magnetic resonance image (MRI) showed a thrombosed mass on the right cerebellar peduncle, and angiography showed no filling of the right SCA from its origin. A follow up angiogram 9 month after endovascular surgery for other aneurysms showed no recanalization of SCA or the aneurysms. There are no previous reports of total spontaneously thrombosed non-giant aneurysms of the distal segment of the SCA.

Cerebellum↗

PubMed2001

Hemoglobin-vesicles as oxygen carriers: influence on phagocytic activity and histopathological changes in reticuloendothelial system.

Hemoglobin-vesicles (HbV) have been developed for use as artificial oxygen carriers (particle diameter, 250 nm) in which a purified Hb solution is encapsulated with a phospholipid bilayer membrane. The influence of HbV on the reticuloendothelial system was studied by carbon clearance measurements and histopathological examination. The HbV suspension ([Hb] = 10 g/dl) was intravenously infused in male Wistar rats at dose rates of 10 and 20 ml/kg, and the phagocytic activity was measured by monitoring the rate of carbon clearance at 8 hours and at 1, 3, 7, and 14 days after infusion. The phagocytic activity transiently decreased one day after infusion by about 40%, but it recovered and was enhanced at 3 days, showing a maximum of about twice the quiescent level at 7 days, and then returned to the normal value at 14 days. The initial transient decreased activity indicates a partly, but not completely, suppressed defensive function of the body. The succeeding increased phagocytic activity corresponds to the increased metabolism of HbV. The histopathological examination with anti-human Hb antibody, hematoxylin/eosin, and oil red O stainings showed that HbV was metabolized within 7 days. Hemosiderin was very slightly confirmed with Berlin blue staining at 3 and 7 days in liver and spleen, though they completely disappeared at 14 days, indicating that the heme metabolism, excretion or recycling of iron proceeded smoothly and iron deposition was minimal. Electron microscopic examination of the spleen and liver tissues clearly demonstrated the particles of HbV with a diameter of about 1/40 of red blood cells in capillaries, and in phagosomes as entrapped in the spleen macrophages and Kupffer cells one day after infusion. The vesicular structure could not be observed at 7 days. Even though the infusion of HbV modified the phagocytic activity for 2 weeks, it does not seem to cause any irreversible damage to the phagocytic organs. These results offer important information for evaluating the safety issues of HbV for clinical use.

Animals↗

PubMed2001

Expression and localization of MGP in rat tooth cementum.

Tooth cementum, a calcified hard tissue covering the root surfaces, is an important component connecting the teeth to the collagenous fibres of the periodontal ligament. Although the overall composition of cementum may closely resemble that of bone, each part has not been fully characterized. Here, the localization of the matrix gamma-carboxyglutamic acid (Gla) protein (MGP), one of the major Gla-containing proteins in the body, in cementum was investigated using immunohistochemistry and in situ hybridization. (1) Strong MGP antigenicity was observed in the acellular cementum, but was only moderate in the cellular cementum; (2) polygonal periodontal ligament cells facing the acellular cementum and the uncalcified cellular cementum expressed MGP mRNA, indicating that these cells produced MGP and deposited it on the cementum; (3) MGP accumulated at the junction between the uncalcified and calcified cellular cementum; and (4) the distribution pattern of MGP antigenicity resembled that of osteopontin. As one function of MGP could be as a negative regulator for mineral apposition, the expression of MGP in the cells adjacent to the cementum may be important to prevent hyperapposition of minerals.

Animals↗

PubMed2001

Molecular detection of tumor cells at diagnosis invading the bone marrow and peripheral blood of patients with aggressive or indolent lymphomas.

We studied tumor cell invasions of bone marrow and peripheral blood in patients with various types of advanced non-Hodgkin's lymphoma by amplifying complementarity determining region III using the polymerase chain reaction (PCR) method and developing patient-specific probes. After molecular engineering, we could detect tumor cells in bone marrow from seven of 11 cases and in peripheral blood from six of 11 cases, despite negative results in four cases studied morphologically. Indolent cases were more likely to yield positive results than aggressive cases. The reason may be different biological behaviors among the histological types.

Bone Marrow Neoplasms↗

PubMed2001

Modification of virus infectivity by cytoplasmic tail of HIV-1 TM protein.

Envelope glycoprotein incorporation is an essential process in formation of infectious particles of human immunodeficiency virus. Accumulated data have indicated that the cytoplasmic tail of Env gp41 is required for efficient incorporation. By analyzing mutant viruses with truncated cytoplasmic tails, we found that the domain was required in a cell-type-dependent manner for maintaining virus infectivity. Although the viruses with truncated cytoplasmic tails produced from HeLa, A3.01 and SupT1 cells showed a greatly reduced infectivity, those from SW480 and MT-4 cells retained a significant infectivity. To clarify the different effect of the cytoplasmic tail mutation on virus infectivity, we performed biochemical studies on the virions produced from HeLa and SW480 cells. Although the truncation of cytoplasmic tail appeared to reduce the Env incorporation in both cell lines, it caused a significant incorporation of Env precursor with HeLa cells. The results suggested that the cytoplasmic tail regulated selective incorporation of processed Env into virions in a cell-type-dependent manner.

Cell Line↗

PubMed2001

Clinical features and alterations in the inferior horn sizes in lateral ventricle in Alzheimer's patients with different ApoE genotype in Japanese population.

E4 allele of Apolipoprotein E (ApoE) is considered to be not only a risk factor for Alzheimer's disease (AD) but also a determinant of clinical features in AD. However, it is still controversial whether ApoE e4 allele is related to age at onset, severity of memory impairment or brain morphological changes in AD patients. The present study examined the issue in Japanese population: 1) ApoE genotype on in 38 normal controls and 32 AD patients; 2) association between e4 allele of ApoE and clinical features including Wechsler Memory Scale-Revised in 32 AD patients; and 3) association between e4 allele of ApoE and change in size of inferior horn in lateral ventricle (LV) in 13 out of 32 AD patients. The e4 allele of ApoE frequency was higher in AD patients than in normal controls. There was no significant difference in age at onset or neuropsychological results between AD with and without e4 allele of ApoE. Alteration per month of the inferior horn sizes in LV measured by MRI was similar in the AD patients with and without e4 allele of ApoE. These results suggest that e4 allele of ApoE is a risk factor but not a determinant of clinical features for AD in Japanese population.

Aged↗

PubMed2001

Improvement of afterload mismatch of left atrial booster pump function with positive inotropic agent.

OBJECTIVES: The objective of this study was to examine the hypothesis that a positive inotropic agent improves left ventricular (LV) filling during left atrial (LA) contraction in the presence of markedly elevated LV filling pressure. BACKGROUND: In patients with old myocardial infarction (MI), an increase in the operational LV chamber stiffness reduces LV filling during the LA contraction, resulting from an "afterload mismatch" of the LA booster pump function. METHODS: We investigated the effect of dobutamine infusion (3 microg/kg/min) on the LA pump function in the presence of elevated LV filling pressure induced by aortic constriction (Aoc) during acute MI in 10 dogs. Transmitral flow velocity was determined by transesophageal echocardiography, LV pressure by a micromanometer and LV volume by a conductance catheter. We measured the early (E) and late (A) diastolic peak transmitral flow velocities (cm/s) and LV chamber stiffness (deltaP/deltaV: mm Hg/ml; where deltaP is developed pressure and deltaV is the absolute filling volume during LA contraction). RESULTS: When the deltaP/deltaV was increased by Aoc during MI (from 1.1 +/- 0.8 to 3.1 +/- 2.6 mm Hg/ml, p < 0.01), A decreased significantly (from 30 +/- 5 to 22 +/- 8 cm/s, p < 0.01), and the ratio of E to A increased (from 1.0 +/- 0.3 to 1.4 +/- 0.8, p < 0.05) compared with MI without Aoc, showing the pseudonormal transmitral flow pattern, the so called "LA afterload mismatch." Dobutamine under this condition significantly reduced the deltaP/deltaV (to 1.7 +/- 1.2 mm Hg/ml, p < 0.05), resulting in an increase in A (to 31 +/- 8 cm/s, p < 0.01) and a decrease in E/A (to 1.0 +/- 0.3, p < 0.05), and the transmitral flow became a prolonged relaxation pattern as in MI without Aoc in all dogs. There was an inverse correlation between the deltaP/deltaV and the time-velocity integral of A (r = -0.70, p < 0.01). CONCLUSIONS: Dobutamine improved the afterload mismatch of the LA booster pump function. This effect may have been due to the reduction in LV operational chamber stiffness, resulting in an increase in the LA forward ejection into the LV.

Animals↗

PubMed2001

Type I and type III procollagen gene expressions in the early phase of ligament healing in rabbits: an in situ hybridization study.

The purpose of this study is to observe type I and type III procollagen gene expressions in the healing ligament using in situ hybridization histochemistry. The rabbit medial collateral ligaments were incised and harvested at 3, 7, 14, and 28 days postoperatively. The healing ligament showed increased expression of both procollagen genes through this period compared with the unoperated ligament. The peak expression level was observed at 7 or 14 days for type I and at 7 days for type III, respectively. The strongest expression of both genes was detected in the scar tissue created between the ends of the old ligament. Although type III procollagen gene expression was observed almost only in the newly created scar tissue, type I procollagen gene was expressed not only in the scar tissue, but also at the ends of the previously normal ligament. These results suggest that type I collagen synthesis begins shortly after ligament injury and occurs at the ends of the injured ligament as well as in the scar tissue, and that type III collagen is largely synthesized in the scar tissue around one week after injury but continues being synthesized for at least four weeks after injury.

Animals↗

PubMed2001

Immature osteoblastic cells express the pro-alpha2(XI) collagen gene during bone formation in vitro and in vivo.

Type XI collagen is predominantly found in cartilage. However, expression of the pro-alpha2(XI) collagen gene (COL11A2) has recently been detected in various non-cartilaginous tissues. We identified the differentiation stage at which COL11A2 was expressed in cultured fetal rat calvarial (FRC) cells and in rat femoral fracture calluses in order to investigate the involvement of COL11A2 during bone formation in vitro and in vivo. We also studied the alternative splicing of exons 6-8 in FRC cells and fracture calluses. In FRC cells, mineralized nodules stained with von Kossa stain were observed from day 9 after confluence. COL11A2 was highly expressed on days 0 and 5, but the expression levels were rapidly decreased on day 9 by Northern blot analysis. During rat femoral fracture repair, intramembranous ossification proceeded and newly formed woven bone was observed on the cortex on day 7 after fracture. In situ hybridization showed that COL11A2 signals were detected in osteoblastic cells in the newly formed woven bone. According to the maturation and remodeling of the woven bone into the trabecular bone, the distribution of the signal for COL11A2 mRNA was limited to the superficial osteoblastic cells of the newly formed trabecular bone. These results demonstrated that COL11A2 was expressed in relatively immature osteoblastic cells during bone formation in vitro and in vivo. RT-PCR showed that the shortest band corresponding to mRNA lacking exons 6-8 was clearly detected when using RNA from soft calluses. In contrast, the largest band corresponding to mRNA with exons 6-8 was predominant when using RNA from FRC cells or from hard calluses on days 7 and 14. These results indicate that the splicing pattern of exons 6-8 in osteoblastic cells is different from the pattern in chondrocytes.

Alternative Splicing↗

PubMed2001

Expression of p53 tumor suppressor gene in adenoid cystic and mucoepidermoid carcinomas of the salivary glands.

Seventeen adenoid cystic carcinomas (ACCs) and 27 mucoepidermoid carcinomas (MECs) occurring in the salivary glands were analyzed for p53 tumor suppressor gene alteration (exons 5-8) and protein expression. The cell proliferation activity was also examined by Ki-67 immunohistochemistry. The p53 alterations were detected in three samples (17.6%) of ACC and in four samples (14.8%) of MEC, and were only found in carcinomas arising in the minor salivary glands. The occurrence of the p53 gene alteration is less frequent in ACC and MEC than that in other kinds of tumors, and therefore does not seem to play a critical role in the course of the tumorigenesis in ACC and MEC. All ACC samples arising from the minor salivary glands exhibiting p53 gene alterations showed recurrence/metastasis, thus suggesting a poor outcome of these patients. All ACCs and three out of four MECs samples with p53 gene alterations showed the lowest degree of p53 immunostaining ratio, thus suggesting that no correlation exists between the p53 gene alterations and the p53 immunostaining in these salivary gland carcinomas. No significant relationship was demonstrated between the immunostaining ratio of either p53 or Ki-67 and the morphological growth pattern or patient clinical course in the ACC samples. The p53 immunopositivity in MEC correlated to the histological grade. The Ki-67 immunostaining ratio was also significantly related to the histological grade and the clinical course in MEC.

Adult↗

PubMed2001

First report of Trichinella nativa in red foxes (Vulpes vulpes schrencki) from Otaru City, Hokkaido, Japan.

Forty-three red foxes (Vulpes vulpes schrencki) and nine raccoon dogs (Nyctereutes procyonoides viverrinus) were captured in Otaru City, Hokkaido, Japan and examined by muscle digestion for the presence of Trichinella sp. larvae. Of the foxes, five (11.6%) were positive for larvae of Trichinella nativa while none of the raccoon dogs were found to be positive. This finding suggests that the red foxes are important reservoir hosts of sylvatic trichinellosis in Otaru, Hokkaido. This is the first report on Trichinella nativa in wild red foxes of Hokkaido, Japan.

Animals↗

PubMed2001

Impairment of an event-related potential correlate of memory in schizophrenia: effects of immediate and delayed word repetition.

OBJECTIVE: We investigated the nature of the memory impairment in schizophrenia using an event-related potential (ERP). METHODS: Visual ERPs were recorded while 20 schizophrenics and 20 controls performed semantic categorization tasks with incidental word repetitions. Participants responded to occasional target words. Half of the non-target words were repeated immediately after initial presentation (lag 0) or after 5 intervening words (lag 5). RESULTS: In both groups, ERPs to words at lag 0 were more positive than those to non-repeated words, though this positive-going effect was attenuated in the schizophrenics, especially around 400-500 ms. The effect at lag 5 was smaller and shorter than that at lag 0 but was comparable between groups. Attenuation of the N400 peak occurred for word repetition at lag 0 in controls but not in schizophrenics, whereas a peak increment in the late positive component induced by word repetition at both lags was observed in both groups. CONCLUSIONS: Findings indicate that patients with schizophrenia have a deficit in a brain process modulating ERP correlates of memory, when words are repeated immediately. This deficit might be related to an abnormal N400 priming effect in schizophrenia.

Adult↗

PubMed2001

Site specificity of the Arabidopsis METI DNA methyltransferase demonstrated through hypermethylation of the superman locus.

Plants with low levels of DNA methylation show a range of developmental abnormalities including homeotic transformation of floral organs. Two independent DNA METHYLTRANSFERASEI (METI) antisense transformants with low levels of DNA methylation had flowers with increased numbers of stamens which resembled flowers seen on the loss-of-function superman (sup) mutant plants and on transgenic plants that ectopically express APETALA3 (AP3). These METI antisense plants have both increased and decreased methylation in and around the sup gene, compared with untransformed controls. DNA from the antisense plants was demethylated at least 4 kb upstream of the sup gene, while there was dense methylation around the start of transcription and within the coding region of this gene; these regions were unmethylated in control DNA. Methylation within the sup gene was correlated with an absence of SUP transcripts. The pattern and density of methylation was heterogeneous among different DNA molecules from the same plant, with some molecules being completely unmethylated. Methylcytosine occurred in asymmetric sites and in symmetric CpA/TpG but rarely in CpG dinucleotides in the antisense plants. In contrast, segregants lacking the METI antisense construct and epimutants with a hypermethylated allele of sup (clark kent 3), both of which have active METI genes, showed a higher frequency of methylation of CpG dinucleotides and of asymmetric cytosines. We conclude that METI is the predominant CpG methyltransferase and directly or indirectly affects asymmetric methylation.

Arabidopsis↗

PubMed2001

Expression of Set-alpha during morphogenesis of mouse lower first molar.

The detailed in situ expression pattern of the Set-alpha gene has been studied. Previously we showed that Set-alpha is a differentially expressed gene in the embryonic mouse mandible at day 10.5 (E10.5) gestational age. Cells expressing Set-alpha were widely distributed in both the epithelial and underlying ectomesenchymal cells at E10.5. At E12, they were slightly aggregated in an area where tooth germ of the lower first molar is estimated to be formed. At E13.5, Set-alpha was strongly expressed in the tooth germ. At the cap stage, Set-alpha was expressed in the enamel organ and dental papilla. At the bell stage, Set-alpha was distinctly expressed in the inner enamel epithelial and dental papilla cells facing the inner enamel epithelial layer, which were intended to differentiate into ameloblasts and odontoblasts, respectively. Interestingly, Set-alpha was also expressed in several embryonic craniofacial tissues derived from the ectoderm. This study is the first report that Set-alpha is distinctly expressed in the developing tooth germ, and suggests that Set-alpha plays an important role in both the initiation and the growth of the tooth germ, as well as in the differentiation of ameloblasts and odontoblasts.

Animals↗

PubMed2001

Localization of activated caspase-3-positive and apoptotic cells in the developing tooth germ of the mouse lower first molar.

This study examined the immunohistochemical detection of activated caspase-3, and its association with apoptosis, during tooth morphogenesis of the mouse lower first molar. The distribution of cells positive for caspase-3 closely corresponded with the localization of the terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate-biotin nick end labelling (TUNEL)-positive apoptotic cells through the developmental course of tooth germs from embryo day 12 (E12) to E19, thus showing that the apoptosis occurring in the developing odontogenic tissue was induced by the activation of the caspase family. The specific distribution pattern of apoptotic cells in the developing odontogenic epithelial tissue from the initiation (E12) of tooth germ to the completion of tooth crown morphology (E19) also suggests that apoptotic events are related not only to a deletion of functionally suspended cells, but also participate in initiation and the completion of tooth morphogenesis. Electron microscopic examination revealed that apoptotic cells were present in the primary enamel knot, and these apoptotic cells were phagocytized by neighbouring odontogenic epithelial cells, thus indicating the prompt disposal of any dead cells by epithelial cells.

Animals↗

PubMed2001

Augmented acetylcholine-induced translocation of RhoA in bronchial smooth muscle from antigen-induced airway hyperresponsive rats.

Acetylcholine (ACh)-induced translocation of RhoA in bronchial smooth muscle of repeatedly antigen-challenged rats that have a marked airway hyperresponsiveness (AHR) was examined. ACh induced time- and concentration-dependent translocation of RhoA to the plasma membrane, indicating an activation of RhoA in bronchial smooth muscle. The level of ACh-induced RhoA translocation was further increased markedly in the AHR group as compared to that in the control group. It is suggested that the augmented activation of RhoA observed in the hyperresponsive bronchial smooth muscle might be responsible for the enhanced ACh-induced Ca(2+) sensitization of bronchial smooth muscle contraction associated with AHR.

Acetylcholine↗