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Biomedical subjects

C Yoshida

Publications and source records attributed to C Yoshida.

At least 19 recordsLinked to original sources

Relationship between aging and susceptibility of erythrocytes to oxidative damage: in view of nutraceutical interventions.

Twelve (12) healthy elderly subjects were divided into two groups: (a) those given an antioxidant/NO-modulating fermented papaya preparation (FPP) 9 g/day for 4 weeks, and (b) a placebo group. No protein/lipid distribution in erythrocytes (RBC) membranes was noted among different ages and treatments. Higher RBC concentration of malondialdehyde and nitric oxide synthase were found in the elderly (p < 0.05 versus "young" controls), whereas superoxide dismutase was unaltered. Such abnormalities were prevented by FPP supplementation (p < 0.01). RBC and RBC ghosts showed an enhanced susceptibility to lipid peroxidation by using cumene hydroperoxide (p < 0.01 versus young) but FPP supplementation significantly protected intact RBC (p < 0.05). These preliminary data suggest that nutraceuticals with antioxidant/NO-regulating properties significantly protect from RBC oxidative damage, and are potential weapons for the aging process and chronic and degenerative diseases.

Aged↗

Some characteristics of primary and secondary oestrous signs in high-producing dairy cows.

Shortened and weakened oestrous signs in dairy cows may cause a failure of oestrus detection and artificial insemination timing error leading to poor reproductive performance. The aims of this study were to investigate the duration of standing oestrus in high-producing dairy cows under a free stall system, to determine the duration of expression of secondary oestrous signs before and after standing oestrus (Expt 1) and to compare the duration and intensity of oestrus between cows and heifers (Expt 2). Cattle were checked for primary and secondary oestrous signs at an interval of 4 h. Heat detection aids were also used. In Expt 1, of 56 cows which were detected in oestrus, 36 cows (64.3%) showed standing oestrus and other 20 cows (36.6%) showed secondary oestrous signs only. Duration of the standing oestrus was 6.6 +/- 6.3 h on average (+/-SD), ranging between 2 and 32 h. The cows in standing oestrus showed secondary oestrous signs during a period from 9.6 +/- 8.1 h before onset of standing to 18.4 +/- 18.8 h after the end of standing oestrus. In the cows that did not show standing oestrus, expression of secondary oestrous signs were observed for 25.7 +/- 20.5 h, which was 7.5 h shorter than the average duration of oestrus in cows showing standing oestrus. In Expt 2, nine (82%) of the 11 lactating cows in oestrus showed standing, while all the 10 heifers exhibited standing oestrus. Average duration of standing oestrus was 6.4 +/- 4.3 h in cows and 6.2 +/- 3.9 h in heifers, respectively. It may be concluded that the duration of standing oestrus is substantially shortened in lactating dairy cows, and more than one-third of cows did not show standing oestrus. In cows showing standing oestrus, duration of expression of secondary oestrous signs before and after standing is not shortened. Duration of standing oestrus in heifers was as short as that in cows.

Animal Husbandry↗

The aging/precancerous gastric mucosa: a pilot nutraceutical trial.

The aim of this study was to test the effect of antioxidant supplementation on enzymatic abnormalities and free radical-modified DNA adducts associated with premalignant changes in the gastric mucosa of elderly patients with HP-negative atrophic gastritis (CAG). Sixty patients with atrophic gastritis and intestinal metaplasia underwent a nutritional interview and a gastroscopy with multiple biopsy samples in the antrum that were processed for histology and for assaying: alpha-tocopherol, MDA, xanthine oxidase (XO), ornithine decarboxylase (ODC), and 8-OHdG. Patients were randomly allocated into three matched groups and supplemented for 6 months with (1) vitamin E, 300 mg/day; (2) multivitamin, two tablets t.i.d.; and (3) Immun-Age 6 g/day nocte (ORI, Gifu, Japan), a certified fermented papaya preparation with basic science-validated antioxidant/immunomodulant properties. Ten dyspeptic patients served as controls. Histology and biochemistry were blindly repeated at 3 and 6 months. CAG patients showed a significantly (P <.05) increased level of mucosal MDA and XO concentration that were reverted to normal by each supplementation (P <.05). All supplements caused a significant decrease of ODC (P <.01), but Immun-Age yielded the most effective (P < 0.05) and was the only one significantly decreasing 8-OhdG (P < 0.05). These data suggest that antioxidant supplementation, and, namely, Immun-Age, might be potential chemopreventive agents in HP-eradicated CAG patients and especially in the elderly population.

8-Hydroxy-2'-Deoxyguanosine↗

Incidence of silent ovulation in dairy cows during post partum period.

The present study was undertaken to show the incidence of silent ovulation in high producing dairy cows, by monitoring ovarian cyclicity based on practical milk progesterone assay which was established in this study. The direct milk progesterone enzyme linked immunosorbent assay (ELISA) was developed using anti-progesterone-3(E)-carboxymethyloxime-BSA antibody for the antibody and horse radish peroxidase labeled progesterone for tracer. High sensitivity (26 pg/mL, 0.65 pg/well), high recovery rates (83-97%), high reproducibility (CV of intra-assay 4.8-11.5%; CV of inter-assay 14.3-19.1%) and high correlation between milk progesterone concentrations measured by the direct ELISA and the values obtained by the ELISA after extraction proved the reliability of the assay. In second experiment the incidence of silent ovulation was investigated based on the milk progesterone concentrations in 32 dairy cows within 70 days post partum. The incidences of silent ovulation at the first, second, third and fourth ovulation post partum were 83, 46, 13 and 0%, respectively. Most commonly observed patterns of sequential occurrence of silent ovulation in cows ovulating 2, 3 or 4 times within 70 days post partum were silent-estrus (50%), silent-silent-estrus (60%) and silent-silent-estrus-estrus (67%), respectively. These results suggest that the present ELISA is a reliable and practically applicable method for determination of progesterone in milk and that high producing dairy cows show a high incidence of silent ovulation at the first post partum ovulation as well as the second ovulation, which then decreased with the increased frequency of ovulation.

Animals↗

Chorioamnionitis caused by Serratia marcescens in a non-immunocompromised host.

A 26 year old pregnant woman with antithrombin III deficiency developed recurrent septicaemia with Serratia marcescens. In spite of the administration of antibiotics, high grade fever persisted. She subsequently manifested lower abdominal pain, and spontaneous abortion occurred. After the abortion, she became completely afebrile. The amnion was turbid, and microscopic examination of the placenta showed haemorrhage and massive infiltration of neutrophils, suggestive of infectious chorioamnionitis. Pulsed field gel electrophoresis showed that isolates from the blood, urine, and vaginal discharge were genetically identical. Intravenous pyelography revealed that she had a bilateral completed double ureter. It was thought that a urinary tract anomaly caused infection with S marcescens, and the pathogen spread to the chorioamnion via the bloodstream. This is the first report of chorioamnionitis caused by S marcescens in a non-immunocompromised host. In addition, these findings indicate that the chorioamnion can serve as a site for persistent infection in normal pregnancies.

Abortion, Spontaneous↗

High-dose chemotherapy and autologous peripheral blood stem cell transplantation for treatment of unspecified peripheral T-cell lymphoma presented with hepatosplenomegaly and hypercytokinemia syndrome: report of three cases.

We report here three cases of peripheral T-cell lymphoma unspecified (PTCL-US), which presented with bone marrow infiltration and hepatosplenomegaly and were successfully treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were all characterized by cytokine-induced symptoms such as fever, anasarca, cytopenia, poor general condition, and disseminated intravascular coagulation syndrome. Laboratory data showed extremely high levels of soluble interleukin-2 receptor, beta(2)-microglobulin, and ferritin. All three patients were negative for anti-adult T-cell leukemia antibody. In one patient, hemophagocytosis was revealed by a histological examination of the bone marrow. The International Prognostic Index was high for all three patients, and they all achieved complete remission after the intensive chemotherapy for remission induction. During complete remission, they were treated with HDCT [modified interleukin-converting enzyme regimen] followed by auto-PBSCT. The recovery of hematopoiesis after auto-PBSCT was prompt and sustained engraftment was obtained. No serious adverse effects other than myelosuppression were noted. One patient died due to cerebrovascular disease without relapse 18 months after auto-PBSCT. The other two patients are still alive and have not suffered from relapse. Our observations suggest that auto-PBSCT following HDCT may be an effective and safe therapeutic modality for high-risk PTCL-US patients characterized by hepatosplenomegaly and cytokine-induced syndrome.

Aged↗

Fournier's gangrene after unrelated cord blood stem cell transplantation.

A 16-year-old boy with refractory acute myelogenous leukemia developed Fournier's gangrene as an early complication after two-antigen HLA-mismatched unrelated cord blood stem cell transplantation. On day 25 after the transplantation, he noted abrupt onset of penile swelling with miction pain. The penile inflammation rapidly extended posteriorly to involve the scrotum and perianal tissues, inferiorly to involve the thighs, and superiorly up the lower abdominal region within the next 36 h, and he died from sepsis on day 27. Fournier's gangrene presenting as a genitoperineal necrotizing fasciitis should be considered as a potential complication in umbilical-cord blood recipients in the cytopenic post-transplant phase.

Adolescent↗

Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures.

Targeted disruption of core binding factor alpha1 (Cbfa1) showed that Cbfa1 is an essential transcription factor in osteoblast differentiation and bone formation. Furthermore, both in vitro and in vivo studies showed that Cbfa1 plays important roles in matrix production and mineralization. However, it remains to be clarified how Cbfa1 controls osteoblast differentiation, bone formation, and bone remodelling. To understand fully the physiological functions of Cbfa1, we generated transgenic mice that overexpressed Cbfa1 in osteoblasts using type I collagen promoter. Unexpectedly, Cbfa1 transgenic mice showed osteopenia with multiple fractures. Cortical bone, which was thin, porous, and enriched with osteopontin, was invaded by osteoclasts, despite the absence of acceleration of osteoclastogenesis. Although the number of neonatal osteoblasts was increased, their function was impaired in matrix production and mineralization. Furthermore, terminally differentiated osteoblasts, which strongly express osteocalcin, and osteocytes were diminished greatly, whereas less mature osteoblasts expressing osteopontin accumulated in adult bone. These data indicate that immature organization of cortical bone, which was caused by the maturational blockage of osteoblasts, led to osteopenia and fragility in transgenic mice, demonstrating that Cbfa1 inhibits osteoblast differentiation at a late stage.

Animals↗

Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes.

During skeletogenesis, cartilage develops to either permanent cartilage that persists through life or transient cartilage that is eventually replaced by bone. However, the mechanism by which cartilage phenotype is specified remains unclarified. Core binding factor alpha1 (Cbfa1) is an essential transcription factor for osteoblast differentiation and bone formation and has the ability to stimulate chondrocyte maturation in vitro. To understand the roles of Cbfa1 in chondrocytes during skeletal development, we generated transgenic mice that overexpress Cbfa1 or a dominant negative (DN)-Cbfa1 in chondrocytes under the control of a type II collagen promoter/enhancer. Both types of transgenic mice displayed dwarfism and skeletal malformations, which, however, resulted from opposite cellular phenotypes. Cbfa1 overexpression caused acceleration of endochondral ossification due to precocious chondrocyte maturation, whereas overexpression of DN-Cbfa1 suppressed maturation and delayed endochondral ossification. In addition, Cbfa1 transgenic mice failed to form most of their joints and permanent cartilage entered the endochondral pathway, whereas most chondrocytes in DN-Cbfa1 transgenic mice retained a marker for permanent cartilage. These data show that temporally and spatially regulated expression of Cbfa1 in chondrocytes is required for skeletogenesis, including formation of joints, permanent cartilages, and endochondral bones.

Animals↗

Enhanced throughput for DNA sequencing by capillary array electrophoresis with a gradient of electric field strength.

The effect of electric field gradients are examined on the speed, selectivity, read length, and accuracy for DNA sequencing using capillary array electrophoresis. Modified electric field gradients was realized to read over 800 bases within 140 min. The method developed is effectively applicable to single nucleotide polymorphism analysis for genomic drug discovery and pharmacogenomics.

Electrophoresis, Capillary↗

Denaturing gradient gel electrophoresis analyses of microbial community from field-scale composter.

The diversity of microbial community during the decomposition of waste in a field-scale composter (Hazaka system) was investigated by denaturing gradient gel electrophoresis (DGGE). The composter operates at a high temperature through a self-heating system, creating a thermophilic (60-76 degrees C) stage during the initial phase and a mesophilic (45 degrees C) stage towards the later phase of the composting period. The pH of the system (pH 7.75-8.10) did not vary significantly during the process while moisture content was reduced from 48.8% to 25.1%. DGGE and 16S rDNA analyses showed that the following genera were found throughout the process: Propionibacterium sp., Methylobacterium sp., Pseudomonas sp., and Bradyrhizobium sp. Different Bacillus spp. thrive at the thermophilic or the mesophilic stage while Clostridium sp. was only found at the initial phase of the process. Staphylococcus sp. and Caulobacter sp. or Brevundimonas sp. existed during the later phase of the composting period.

Journal Article↗

Carcinosarcoma of the tongue with cyclin D1 gene amplification.

Carcinosarcoma of the tongue is a rare malignancy and its molecular aspect is unclear. A case of carcinosarcoma of the tongue in a 51-year-old man is presented. A polypoid tumor of the tongue, measuring 12 x 12 x 6 mm, was resected. Histologically, the tumor was composed of a squamous cell carcinoma and a spindle cell sarcomatous component. We previously showed that one cell-cycle regulator, the cyclin D1 gene, was frequently amplified in esophageal carcinosarcoma, which shows the same morphologic features as carcinosarcoma of the tongue. In this case, we examined whether the cyclin D1 gene is amplified in carcinosarcoma of the tongue as well. Fluorescence in situ hybridization analysis revealed that the cyclin D1 gene was amplified in both components of carcinosarcoma of the tongue. The cyclin D1 protein was also detected by immunostaining in both components. Our results suggest that the amplification of cyclin D1 gene plays a role in the molecular pathogenesis of carcinosarcoma of the tongue, at least in some cases.

Carcinosarcoma↗

Atomic force microscopy proposes a 'kiss and pull' mechanism for enhancer function. off.

The DNase I-hyper-sensitive sites (HS2-HS4) in the beta-globin gene enhancer region (locus control region; LCR) have been known as the target of Bach1/MafK heterodimers. We have demonstrated previously by utilizing atomic force microscopy (AFM) that Bach1/MafK mediates the formation of a looped-DNA structure in the LCR fragment. Here we perform further detailed analyses of the loop structure formed between each HSs by AFM, and propose a novel model for the enhancer/protein interaction: the Bach1/MafK heterodimer preferentially binds to HS2 with highest affinity and to HS3 with lower affinity. However, they assemble to each other to form a stable complex of four heterodimers and mediate a DNA-loop formation. Once the DNA loop is formed between HS2 and HS3, the Bach1/MafK complex at the HS3 side leaves the HS3 and starts to slide along the DNA strand towards HS2 with the other side of the complex fixed at the HS2 region. This 'kiss and pull' model will contribute to understand the function of regulatory proteins at enhancer regions in terms of higher-order structure of DNA, e.g. nucleosomes and chromatin.

Basic-Leucine Zipper Transcription Factors↗

Treatment of chronic hepatitis C in patients who failed interferon monotherapy: effects of higher doses of interferon and ribavirin combination therapy. The Virginia Cooperative Hepatitis Treatment Group.

OBJECTIVE: The present study was designed to evaluate the effectiveness of interferon-ribavirin combination therapy for treatment of chronic hepatitis C virus (HCV) in patients who failed previous treatment with interferon monotherapy. METHODS: A total of 140 patients with well-documented chronic HCV who failed to achieve a virological (if HCV-RNA was assessed) or biochemical response (if HCV-RNA was not assessed) to interferon monotherapy, 3 mU three times weekly (TIW) for 3-18 months, were randomly assigned to one of three treatment groups. Group A patients were treated with 5 mU interferon TIW for 6 months. Ribavirin (1000-1200 mg daily) was added in those patients HCV-RNA positive at month 3. Group B patients were treated with 3 mU interferon TIW plus ribavirin (1000-1200 mg daily) for 6 months. The dose of interferon was increased to 5 mU TIW in those patients HCV-RNA positive at month 3. Group C patients were treated with 5 mU interferon TIW plus ribavirin (1000-1200 mg daily) for 6 months. Serum ALT and HCV-RNA were monitored during and after treatment for a total of 15 months. RESULTS: Seventeen percent of patients in group A became HCV-RNA negative by treatment month 3. Adding ribavirin resulted in one additional patient becoming HCV-RNA negative. However, none of the patients in this group achieved sustained virological response. Twenty-six percent of patients in group B became HCV-RNA negative by treatment month 3. Increasing the dose of interferon from 3 to 5 mU TIW increased virological response to 30%. However, sustained virological response was observed in only 14%. Thirty percent of patients in group C became HCV-RNA negative, but sustained virological response was observed in only 12%. Sustained virological response was found to be significantly greater in patients with a nontype I HCV genotype (p < 0.002) and in patients who had a decline in HCV-RNA titer to a value < 100,000 copies/ml during their previous course of interferon monotherapy (p < 0.0001). None of the 12 sustained responders were African Americans (p < 0.013). CONCLUSIONS: Retreatment of nonresponders with interferon-ribavirin combination therapy results in limited benefit; only 13% of patients achieved sustained virological response. Response was extremely poor in African Americans and those with HCV genotype 1.

Adult↗

Synthesis and antiinflammatory activity of 7-methanesulfonylamino-6-phenoxychromones. Antiarthritic effect of the 3-formylamino compound (T-614) in chronic inflammatory disease models.

A group of derivatives of 7-methanesulfonylamino-6-phenoxychromone (1) at the pyrone and phenoxy rings was synthesized starting with 4-chloro-3-nitroanisole and evaluated against acute and chronic inflammations in oral administration in animals. Significant potency in the rat models of carrageenin-induced edema (CPE) and adjuvant-induced arthritis (AA) was realized with 2'-fluoro and 2',4'-difluoro derivatives (9a and 9d), and 3-formylamino derivative (19a) and its 2'-fluoro and 2',4'-difluoro compounds (22a and 22d), displaying AA therapeutic effect of ED40 = 2.5-7.1 mg/kg/d for 7 d and AA prophylactic effect of 53-70% inhibition at the dosage of 3 mg/kg/d for 22 d. To identify a candidate for further pharmacological study, the five compounds were subjected to evaluation of their gastro-ulcerogenic liability, leading to selection of the fluorine-free compound 19a which did not cause acute ulceration at 300 mg/kg in oral administration in rats. Compound 19a (ED40 = 3.6 mg/kg in established AA) possessed good therapeutic efficacy against type II collagen-induced arthritis in DBA/1J mice with doses of 30 and 100 mg/kg, suggesting the development of 19a (designated T-614) as a prospective disease-modifying antirheumatic agent. In addition, a preparative-scale synthetic route to T-614 has been established.

Animals↗

[Prevention of hepatitis B flare-up using lamivudine in a patient with non-Hodgkin's lymphoma after allogeneic bone marrow transplantation].

A 22-year-old man with non-Hodgkin's lymphoma (B-cell lymphoblastic lymphoma, Stage IVA) received chemotherapy and radiation therapy and achieved complete remission. He was admitted for allogeneic bone marrow transplantation (BMT) using a graft from his completely HLA-matched mother. Although he had HBV infection, allogeneic BMT was performed because he still had normal liver function and strongly requested the procedure. He developed both acute and chronic GVHD after the procedure, but showed no liver damage related to HBV. Treatment with lamivudine (150 mg/day) was started because the HBV-DNA level increased gradually after allogeneic BMT. Although the HBV-DNA then decreased gradually and there was no evidence of severe liver damage, the patient died following relapse of NHL. It seems that in this case, treatment of HBV with lamivudine may have prevented serious liver damage after allogeneic BMT. Therefore, allogeneic BMT may be done safely in patients with HBV infection if lamivudine is administered.

Adult↗

Clinicopathological analyses of 5 Japanese patients with CD56+ primary cutaneous lymphomas.

We analyzed the clinicopathological features of 5 Japanese patients with CD56+ primary cutaneous lymphomas (3 men and 2 women aged 25 to 73 years). Except for 1 patient in whom bone marrow involvement was simultaneously observed, all patients presented with cutaneous lesions. Based on their Epstein-Barr virus (EBV) status, we categorized these patients into 2 groups, namely EBV-encoded small RNA-1 (EBER-1) (3 patients) and EBER-1- (2 patients). Generalized lymphadenopathy and bone marrow involvement were observed only in EBER-1 patients. Morphologically, angiocentric proliferation was more prominent in EBER-1+ patients and was accompanied by panniculitis-like changes. The lymphomas in EBER-1- patients featured monomorphic proliferation of lymphoblastic cells with no cytoplasmic granules. Phenotypically, CD3-, cytoplasmic CD3 epsilon+, and CD56+ were common findings in both types. The EBER-1- type showed an additional distinguishing feature, CD7+, CD4+, CD8-, HLA-DR+, and terminal deoxynucleotidyl transferase-positive (TdT+) phenotype. The lymphoma was primarily resistant in the EBER-1+ type, and the patients died within 6 months of admission. In contrast, the lymphoma in the EBER-1- patients was originally chemosensitive. Collectively, we consider there to be at least 2 types of CD56+ primary cutaneous lymphomas, corresponding to nasal-type natural killer (NK)/T-cell lymphomas (EBER-1+) and blastic NK-cell lymphomas (EBER-1-).

Adult↗