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Biomedical subjects

Hiroko Suzuki

Publications and source records attributed to Hiroko Suzuki.

At least 19 recordsLinked to original sources

Multimodal intervention benefits: Responder analysis of J-MINT PRIME Kanagawa trial.

INTRODUCTION: The J-MINT PRIME Kanagawa trial was an 18-month multimodal intervention (incorporating exercise, nutrition, and metabolic management) for dementia prevention. Because the primary analysis showed no significant benefits, we performed an exploratory responder analysis to identify responsive subpopulations. METHODS: We analyzed the Full Analysis Set comprising 188 participants. Classification and regression tree (CART) analysis, applied to the intervention arm, identified baseline predictors of cognitive improvement. These rules were then applied to the entire cohort to evaluate treatment effects on the Mini-Mental State Examination (MMSE) using fully adjusted mixed-effects models for repeated measures (MMRM). RESULTS: CART identified a "Target Group" (N = 108) characterized by baseline profiles such as an MMSE score < 28 or specific metabolic ranges (e.g., LDL-C < 135 mg/dL). Within this target group, the intervention significantly preserved MMSE trajectories compared with the control group (group &#xd7; time interaction, P = 0.022). In contrast, the Non-Target Group (N = 80), consisting of high-functioning individuals (MMSE &#x2265; 28), exhibited no significant group &#xd7; time interaction. DISCUSSION: Multimodal interventions may effectively preserve global cognition in older adults with sub-threshold cognitive decline. Careful targeting of appropriate populations, while considering potential longitudinal measurement artifacts (e.g., practice effects), is essential. These findings provide a hypothesis-generating framework that warrants external validation in future prevention trials.

Humans↗

Evaluation of S100A10, annexin II and B-FABP expression as markers for renal cell carcinoma.

This study aimed to analyze expression of S100A10, annexin II and B-FABP genes in renal cell carcinoma (RCC) and their potential value as tumor markers. Furthermore, any correlation between the gene expression and prognostic indicators of RCC was analyzed. Expression of each gene was estimated by RT-PCR in the non-neoplastic (normal) and tumorous parts of resected kidney samples. Also, each antigen was immunostained in RCC and normal kidney tissues. Expression of the S100A10 gene averaged 2.5-fold higher in the tumor than that in the normal tissues (n = 47), after standardization against that of beta-actin. However, expression of annexin II, a natural ligand of S100A10, was only 1.64-fold higher. In the tissue sections of RCC, S100A10 and annexin II were immunostained in membranes. In the normal renal epithelia, however, both antigens were stained in the Bowman's capsule and the tubules from Henle's loop through the collecting duct system, but not in the proximal tubules, from where most RCC are derived. In contrast, expression of the B-FABP gene was 20-fold higher in the tumor. No B-FABP was immunohistochemically detected in normal kidney sections, but it was stained in the cytoplasm of RCC tissue sections. S100A10 and B-FABP genes were overexpressed regardless of nuclear grade and stage of RCC. Immunopositivity in RCC tissues (n = 13) was 100% for S100A10 and annexin II, and 70% for B-FABP; however, no clear relationship was observed in either antigen with nuclear grade and stage. It was found that all three performed well as RCC markers. B-FABP was most specific to RCC, as it was expressed little in normal kidney tissues.

Annexin A2↗

Actigraphic predictors of the depressive state in students with no psychiatric disorders.

BACKGROUND: Insomnia is one of the characteristics of the early depressive state. One-third of university students has a mild depressive state. In this study, we examined whether the depressive state would be correlated with the actigraphic-derived daytime activity levels (DAL) and total sleep time (TST) in students with no psychiatric disorders. METHOD: Consenting volunteers were monitored at home for 3-4 days with a wrist actigraph. The DALs for 3 h before noon (DAL-M) and after 13:00 h (DAL-A) were calculated. The states of sleep and wakefulness were judged based on the activity levels, using a special algorithm. On the first day of the recording, the subjects were requested to fill a questionnaire, "Center of Epidemiologic Scale for Depression Scale (CES-D)," to evaluate the severity of their depressive state. RESULTS: There was a significant correlation between the DAL-M and DAL-A in both males (r=0.52, n=27) and females (r=0.50, n=21). TST was significantly correlated with depressive state only in the females (r=-0.49, n=28). In contrast, there was no significant correlation between the DAL and the severity of the depressive state. By multiple regression analysis, TST was only a good predictor of depressive state. CONCLUSION: The results of this investigation suggest that TST could be used as an index of the depressive state. The TST values in this study decreased as the severity of the depressive state increased, which suggests an association between the severity of the depressive state and insufficient sleep.

Activity Cycles↗

Detection and sequence analysis of DNA polymerase and major envelope protein genes in koi herpesviruses derived from Cyprinus carpio in Gunma prefecture, Japan.

Koi herpesvirus (KHV), which is believed to be an emerging virus, causes fatal diseases in carps. Since the 1990s, the presence of KHV has been confirmed in several countries. In Japan, from 2003 to 2004, large outbreaks of KHV infection in farmed carps resulted in the death of numerous fishes. From April to May 2004, we collected 43 dead or dying carps exhibiting typical symptoms of KHV infection in Gunma prefecture. To conduct a molecular epidemiologic study of KHV in our prefecture, we amplified DNA polymerase and the major envelope protein genes of KHV derived from carp gills using newly designed primers. We also performed sequence analysis of both genes of KHV. Sensitivity of our PCR method for amplification of DNA polymerase and the major envelope protein genes of KHV was 3 x 10(2) (100 fg) and 3 x 10(3) (1000 fg) copies of KHV genome, respectively. We detected both DNA polymerase and major envelope protein genes in 37 of 43 carps (86%). No mutation was found in both the genes sequenced from 11 strains, which included two foreign strains and one domestic strain. The results suggested that KHV strains derived from carps in our prefecture were closely related genetically to the other KHV strains.

Animals↗

API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-kappaB binding elements: evidence for a positive feed-back loop pathway resulting in unremitting NF-kappaB activation.

t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-kappaB signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-kappaB binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-kappaB p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)-carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-kappaB activation.

Binding Sites↗

Insomnia as a sequela of sarin toxicity several years after exposure in Tokyo subway trains.

More than 5,000 passengers on Tokyo subway trains were injured with toxic chemicals including the nerve gas "sarin" on March 20, 1995. The purpose of this study was to identify the effect of sarin exposure on insomnia in a cross-sectional study. A self-administered questionnaire concerning sleep-related items was distributed to victims of sarin exposure in October and November, 2003. Questionnaires were completed by 161 of the 163 participants (98.8%), who were selected from 1,500 subjects. Among them, the authors selected 75 women 30 to 69 years of age. Control participants were collected from inhabitants living in Maebachi City, Gunma Prefecture, Japan. For the younger exposed group (under 50 yr. of age), percentages of poor sleep, difficulty falling asleep, intermittent awakening, early morning awakening, a feeling of light overnight sleep, and insomnia were significantly higher than those for the control group. In contrast, the older exposed group (ages 50 to 69 years) had significantly higher prevalence of poor sleep, a feeling of light overnight sleep, and early morning awakening for the exposed group when compared with the control group. The high prevalence of insomnia and insomnia-related factors for victims especially under 50 years of age suggests a need for research on sleep quality after sarin exposure. Although posttraumatic stress disorder is assumed to be a psychological effect of exposure to a toxic substance, a cause-and-effect relationship has not been established.

Adult↗

Lipid compositions of human gastric fluid and epithelium: the role of sulfated lipids in gastric cytoprotection.

BACKGROUND: Gastric sulfatide, whose carbohydrate moiety resembles that of the anti-ulcer drug sucralfate, has been shown to play a role in mucosal protection in an experimental ulcer model. To elucidate the functional significance of gastric lipids, precise determination of the lipids in human gastric fluid and epithelium was performed, and the anti-ulcer effects of all lipids in the fluid were measured in mouse ulcer models. METHODS: The lipids in human gastric fluid and epithelium were analyzed by thin layer chromatography and immunostaining, and the anti-ulcer effects of gastric lipids were determined using mouse ulcer models. RESULTS: Human gastric epithelium contained both sulfatide and cholesterol sulfate (CS) as sulfolipids, which were also detected in gastric fluid, showing their stable natures in the gastric fluid. Hemorrhaging in HCl-induced gastric lesions was suppressed in a dose-dependent manner by the administration of sulfolipid-containing liposomes, but suppression of stress ulcers was only accomplished with CS-containing liposomes, ie, not with sulfatide-containing ones, due to the longer retainment of CS than sulfatide in the stomach. CONCLUSIONS: Among the lipids in human gastric fluid, CS was revealed to exhibit a gastroprotective activity, which was more effective than that of sulfatide.

Adult↗

Thermoadaptation trait revealed by the genome sequence of thermophilic Geobacillus kaustophilus.

We present herein the first complete genome sequence of a thermophilic Bacillus-related species, Geobacillus kaustophilus HTA426, which is composed of a 3.54 Mb chromosome and a 47.9 kb plasmid, along with a comparative analysis with five other mesophilic bacillar genomes. Upon orthologous grouping of the six bacillar sequenced genomes, it was found that 1257 common orthologous groups composed of 1308 genes (37%) are shared by all the bacilli, whereas 839 genes (24%) in the G.kaustophilus genome were found to be unique to that species. We were able to find the first prokaryotic sperm protamine P1 homolog, polyamine synthase, polyamine ABC transporter and RNA methylase in the 839 unique genes; these may contribute to thermophily by stabilizing the nucleic acids. Contrasting results were obtained from the principal component analysis (PCA) of the amino acid composition and synonymous codon usage for highlighting the thermophilic signature of the G.kaustophilus genome. Only in the PCA of the amino acid composition were the Bacillus-related species located near, but were distinguishable from, the borderline distinguishing thermophiles from mesophiles on the second principal axis. Further analysis revealed some asymmetric amino acid substitutions between the thermophiles and the mesophiles, which are possibly associated with the thermoadaptation of the organism.

Adaptation, Physiological↗

Antiapoptotic function of apoptosis inhibitor 2-MALT1 fusion protein involved in t(11;18)(q21;q21) mucosa-associated lymphoid tissue lymphoma.

t(11;18)(q21;q21) is a characteristic chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in fusion transcript of apoptosis inhibitor 2 (API2), also known as c-IAP2, and MALT translocation gene 1 (MALT1). Although the API2-MALT1 fusion protein has been shown to enforce activation of nuclear factor kappaB signaling, its precise role in the apoptotic signaling pathway remains to be established. To identify proteins that bind the API2-MALT1 protein, we used coimmunoprecipitation and SDS-PAGE, followed by liquid chromatography-electrospray ionization tandem mass spectrometry. As a result, three important regulators of apoptosis, Smac, HtrA2, and TRAF2, and three other proteins were identified as potential API2-MALT1-binding proteins. Immunoprecipitation analyses verified that API2-MALT1 indeed binds to both exogeneous and endogeneous Smac proteins. It is especially noteworthy that stably transfected API2-MALT1 significantly suppressed both UV- and etoposide-induced apoptosis in HeLa cells, thus demonstrating for the first time that API2-MALT1 indeed possesses antiapoptotic function. Furthermore, API2-MALT1 significantly suppressed Smac-promoted apoptosis in UV-irradiated HeLa cells. Thus, our results provide direct experimental evidence that API2-MALT1 can confer resistance to apoptosis, at least in part, by neutralizing apoptosis promoted by Smac.

Amino Acid Sequence↗

Landiolol attenuates acute hemodynamic responses but does not reduce seizure duration during maintenance electroconvulsive therapy.

Maintenance electroconvulsive therapy (mECT) is an outpatient procedure that requires further consideration in terms of management of ambulatory anesthesia. Although many adjunctive drugs for stabilizing hemodynamic changes during ECT have been reported, side-effects of these drugs may delay recovery and discharge from hospital. The effects of landiolol, a novel ultra-short-acting beta-adrenergic blocker, have been measured on seizure duration, hemodynamic changes, recovery from anesthesia, and cognitive function during mECT under propofol anesthesia. A total of 10 patients with depression in the remission phase, were studied in a randomized, double-blind, placebo-controlled, crossover manner. Administration of 0.1 mg/kg of landiolol immediately before anesthesia significantly blunted the increase in heart rate and blood pressure during convulsions compared with placebo; landiolol was not associated with excessive hypotension or bradycardia. Landiolol did not affect seizure duration, recovery from anesthesia, or cognitive function before or after ECT. These results suggest that landiolol can be used effectively and safely during mECT.

Adrenergic beta-Antagonists↗

Short leg brace and stroke rehabilitation.

OBJECTIVE: We looked for the patients who were treated by short leg brace (SLB) in our hospital for the effects on the treatment of stroke. METHOD: Patients admitted to our hospital for the purposes of rehabilitation of stroke and had SLB prescription from October 2001 to October 2003 were investigated. A total of 20 patients (19 men, 11 women) were investigated in this study. Average age was 60.8 +/- 8.60 years old. Diagnoses were cerebral hemorrhage (12), brain infarction (7), and subarachnoid hemorrage (2). There was right hemiparesis in 15 patients, and left hemiparesis in 15. Activities of daily living (ADLs) were evaluated by FIM at admission and at discharge. The difference between these FIM scores was recorded as DeltaFIM. The levels of ambulation were classified into "need help," "need observation," and "self-sufficient." At the same time, the need for walking aid was recorded. To determine the effects of SLB, all the patients were checked for period of ambulation with cane to the prescription of SLB (period A), period of completion of SLB to acquirement of final walking ability (period B), and Brunnstrom recovery stage for the evaluation of motor recovery. Finally, the level of paralysis, the periods of A and B, ADL assessments, and final ambulation level were investigated. RESULTS: At the time of admisison, the average FIM was 73.9 +/- 24.2; average FIM at time of discharge was 98.2 +/- 21.7. DeltaFIM was 24.3 +/- 21.7. The period A was 37.9 +/- 22.7 days and the period B was 36.8 +/- 24.6 days. The final gait performance was need help, 6; need supervision, 11; and self-sufficient, 13. When we compared Brunnstrom recovery stage III and IV patients and Brunnstrom recovery stage II patients, stage II patients had a longer period A.

Aged↗

Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18) (q21;q21) MALT lymphoma.

t(11; 18) (q21; q21) is a chromosomal aberration specific to low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and generates the chimeric product apoptosis inhibitor 2 (API2)-MALT1, which has been suggested to play an important role in MALT lymphomagenesis. However, little is known about the characteristics of API2, MALT1, and API2-MALT1 proteins. We therefore investigated the subcellular localization and stability of these products. API2 was localized in the nucleus and the cytoplasm, and MALT1 and API2-MALT1 in the cytoplasm only. Western blot analysis showed that the products of API2 and MALT1 were unstable, while the API2-MALT1 product was stable. The API2 deletion mutants at the end of the C-terminal and the MALT1 deletion mutants at the end of the N-terminal were stable compared with the full-length products. These results indicate that the domains responsible for protein instability are located in the end of the C-terminal of API2 and in that of the N-terminal of MALT1, and also that API2-MALT1 became stable because it lacks these domains. It has been suggested that NF-kappaB activation plays an important role in the tumorigenesis of MALT lymphoma. Our findings further suggest that the stabilized expression of API2-MALT1 products may continuously stimulate the NF-kappaB activating pathway, thus leading to MALT lymphomagenesis.

Animals↗

Epidermal growth factor receptor tyrosine kinase inhibition augments a murine model of pulmonary fibrosis.

The inappropriate regeneration of sequentially injured epithelium is an important process leading to pulmonary fibrosis. Previous studies have shown that the epithelial expression of epidermal growth factor receptor (EGFR) is increased in fibrotic lung tissue, compared with normal lung tissue, suggesting that EGFR-mediated signaling is involved in epithelial regeneration in fibrotic lung diseases. We examined the effect of EGFR inhibition using ZD1839, a selective EGFR tyrosine kinase inhibitor (TKI), on bleomycin-induced pulmonary fibrosis in mice. ICR mice were administered a single intratracheal injection of bleomycin (5 units/kg) on day 1. ZD1839 (200 mg/kg) or vehicle alone were administered p.o. 1 h before this injection and on days 1-5 each week for 3 weeks. Lung tissue was harvested on day 21. Lung histology and collagen analysis performed on day 21 showed more severe fibrosis in the mice receiving both bleomycin and the EGFR-TKI than in the mice receiving bleomycin and the vehicle. An immunohistochemistry analysis showed that phosphorylated EGFR and proliferation cell nuclear antigen were highly expressed by the regenerated epithelial cells in the mice treated with bleomycin and the vehicle. In contrast, the expression of these antigens was attenuated in the mice treated with bleomycin and the EGFR-TKI. In vitro studies also demonstrated that the addition of ZD1839 at a concentration of < or =1 microM suppressed the proliferation of type II-like epithelial cells (A549) but not that of lung fibroblasts (IMR90). These results suggest that the inhibition of EGFR phosphorylation augments bleomycin-induced pulmonary fibrosis by reducing regenerative epithelial proliferation. Our data suggest that EGFR-TKIs should be used with caution in cancer patients with pulmonary fibrosis.

Animals↗

[Perinatal psychiatry for mother-infant mental health--perinatal care for untreated patient].

I have presented to our support system, which mainly utilizes the Edinburgh Postnatal Depression Scale (EPDS) at 4 days and 1 month for mothers in the perinatal period and newborn babies, who have been under the care of the Morioka Red Cross Hospital. The perinatal system for mothers and babies, which has evolved over the past 9 years at the Morioka Red Cross Hospital. I explained the case of a 25-year-old woman who had already been suffering from depression before her pregnancy, and the course of improvement she experienced under this support system. In particular, I have shown a means of support, which can be provided by the obstetrics staff and is available to patient and families without making them feel hesitant. We take care of childbirth, and after baby care has started, we encourage depressive mothers to visit the Psychiatric Department. As a result, depression is no longer problematic, and the mothers recover sufficiently to be able to take good care of their babies. Even now, we are keeping track of these mothers and babies, while working together with the public health centers in communities. In the future, we will place emphasis on the implementation of SCID and on the careful observations of mothers and especially, babies, under the room-in system. We are also planning to begin lactation guidance at an earlier stage than before.

Adult↗

Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in T-cell lymphoma/leukemia cell lines.

Chromosome band 6q21 is reported to be one of the most frequent target regions in T-cell lymphoma for both translocations and deletions. To explore whether the breakpoint clustering in T-cell malignancy indicates the presence of a common breakpoint region in 6q, we employed fluorescence in situ hybridization analysis using various YAC, BAC, and PAC clones aligned at 6q21-22. We identified two T-cell lymphoma/leukemia cell lines with different differentiation stages that had breakpoints within the same novel gene, TCBA1 (T-cell lymphoma breakpoint associated target 1). In a T-cell lymphoblastic lymphoma cell line, HT-1, the TCBA1 fused to SUSP1 (SUMO-1-specific protease), creating a SUSP1-TCBA1 chimeric gene. However, in an adult T-cell leukemia cell line, ATN-1, no chimeric gene was detected, although aberrant TCBA1 transcripts were produced. We conclude that TCBA1 is a possible target gene for T-cell lineage-specific chromosome aberrations at 6q21.

Amino Acid Sequence↗

Clinicopathologic comparison between the API2-MALT1 chimeric transcript-positive and -negative gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type.

Little is known about the clinicopathological differences between API2-MALT1 chimeric transcript-positive and -negative gastric low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type. The aim of this study was to clarify those differences in gastric MALT lymphoma. Twenty-three patients with gastric MALT lymphoma were enrolled in a unicenter study. Helicobacter pylori (H. pylori) infection status and clinical stages were investigated. Antibacterial treatment was performed for every patient. Responsiveness of MALT lymphoma to this treatment was assessed by means of regular follow-up endoscopy combined with biopsy. All cases were examined for API2-MALT1 chimeric transcript by means of RT-PCR and sequencing analyses. H. pylori infection status was assessed as positive in 20 patients and negative in three. With regard to responsiveness to antibacterial treatment, complete remission was observed in two patients, partial remission in 12 and no change in nine. API2-MALT1 chimeric transcript was detected in seven patients, all of whom showed no change in response to antibacterial treatment. API2-MALT1 positivity was found to be significantly correlated with responsiveness to antibacterial treatment (P = 0.0001), absence of H. pylori infection (P = 0.0198), and gross cobblestone mucosa observed endoscopically (P = 0.0198). For the other factors (age, sex, dominant site of lesion, high-grade component, infiltrated layer of gastric wall, nodal involvement or clinical stages), there were no differences between API2-MALT1 chimeric transcript-positive and -negative cases. Gastric API2-MALT1 chimeric transcript-positive MALT lymphoma generally features unresponsiveness to antibacterial treatment, and is thought to be unrelated to H. pylori infection in its pathogenesis. Our findings indicate the presence of different clinical subtypes in gastric MALT lymphomas.

Adult↗