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Biomedical subjects

H Ogawa

Publications and source records attributed to H Ogawa.

At least 37 records · Page 2Linked to original sources

Experimental investigation of geologically produced antineutrinos with KamLAND.

The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and 232Th within the Earth. Earth composition models suggest that the radiogenic power from these isotope decays is 16 TW, approximately half of the total measured heat dissipation rate from the Earth. Here we present results from a search for geoneutrinos with KamLAND. Assuming a Th/U mass concentration ratio of 3.9, the 90 per cent confidence interval for the total number of geoneutrinos detected is 4.5 to 54.2. This result is consistent with the central value of 19 predicted by geophysical models. Although our present data have limited statistical power, they nevertheless provide by direct means an upper limit (60 TW) for the radiogenic power of U and Th in the Earth, a quantity that is currently poorly constrained.

Journal Article↗

Tree allometry and improved estimation of carbon stocks and balance in tropical forests.

Tropical forests hold large stores of carbon, yet uncertainty remains regarding their quantitative contribution to the global carbon cycle. One approach to quantifying carbon biomass stores consists in inferring changes from long-term forest inventory plots. Regression models are used to convert inventory data into an estimate of aboveground biomass (AGB). We provide a critical reassessment of the quality and the robustness of these models across tropical forest types, using a large dataset of 2,410 trees >or= 5 cm diameter, directly harvested in 27 study sites across the tropics. Proportional relationships between aboveground biomass and the product of wood density, trunk cross-sectional area, and total height are constructed. We also develop a regression model involving wood density and stem diameter only. Our models were tested for secondary and old-growth forests, for dry, moist and wet forests, for lowland and montane forests, and for mangrove forests. The most important predictors of AGB of a tree were, in decreasing order of importance, its trunk diameter, wood specific gravity, total height, and forest type (dry, moist, or wet). Overestimates prevailed, giving a bias of 0.5-6.5% when errors were averaged across all stands. Our regression models can be used reliably to predict aboveground tree biomass across a broad range of tropical forests. Because they are based on an unprecedented dataset, these models should improve the quality of tropical biomass estimates, and bring consensus about the contribution of the tropical forest biome and tropical deforestation to the global carbon cycle.

Biomass↗

Measurement of neutrino oscillation with KamLAND: evidence of spectral distortion.

We present results of a study of neutrino oscillation based on a 766 ton/year exposure of KamLAND to reactor antineutrinos. We observe 258 nu (e) candidate events with energies above 3.4 MeV compared to 365.2+/-23.7 events expected in the absence of neutrino oscillation. Accounting for 17.8+/-7.3 expected background events, the statistical significance for reactor nu (e) disappearance is 99.998%. The observed energy spectrum disagrees with the expected spectral shape in the absence of neutrino oscillation at 99.6% significance and prefers the distortion expected from nu (e) oscillation effects. A two-neutrino oscillation analysis of the KamLAND data gives Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2). A global analysis of data from KamLAND and solar-neutrino experiments yields Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2) and tan((2)theta=0.40(+0.10)(-0.07), the most precise determination to date.

Journal Article↗

Reduced-intensity hematopoietic stem-cell transplantation for malignant lymphoma: a retrospective survey of 112 adult patients in Japan.

We conducted a nation-wide survey of 112 adult Japanese patients who underwent reduced-intensity stem cell transplantation (RIST) from 1999 to 2002. Underlying diseases included indolent (n=45), aggressive (n=58) and highly aggressive lymphomas (n=9). Median age of the patients was 49 years. A total of 40 patients (36%) had relapsed diseases after autologous stem cell transplantation and 36 patients (32%) had received radiotherapy. RIST regimens were fludarabine-based (n=95), low-dose total body irradiation-based (n=6) and others (n=11). Cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were, respectively, 49 and 59%. Cumulative incidences of progression and progression-free mortality were 18 and 25%, respectively. With a median follow-up of 23.9 months, 3-year overall survival rates were 59%. A multivariate analysis identified three significant factors for progression, which are history of radiation (relative risk (RR) 3.45, confidential interval (CI) 1.12-10.0, P=0.03), central nervous system involvement (RR 6.25, CI 2.08-20.0, P=0.001) and development of GVHD (RR 0.28, CI 0.090-0.86, P=0.026). RIST may have decreased the rate of transplant-related mortality, and GVHD may have induced a graft-versus-lymphoma effect. However, whether or not these potential benefits can be directly translated into improved patient survival should be evaluated in further studies.

Adult↗

Th1-biased humoral immune responses against Wilms tumor gene WT1 product in the patients with hematopoietic malignancies.

The Wilms' tumor gene WT1 is highly expressed in leukemias and myelodysplastic syndrome (MDS), and WT1 expression levels increase along with the disease progression in chronic myeloid leukemia and MDS. We previously reported that IgM and IgG WT1 antibodies were detected with significantly higher detection rate and antibody titers in leukemias and MDS compared to those in healthy volunteers. In this study, whether IgG humoral immune responses against WT1 protein were Th1- or Th2-type were determined by measurement of four subclasses of IgG WT1 antibody, IgG1, IgG2, IgG3, and IgG4. In leukemias and MDS, Th1-type WT1 antibodies such as IgG1, IgG2, and IgG3 were significantly increased in both detection rate and antibody titers compared to those in healthy volunteers, whereas Th2-type WT1 antibody such as IgG4 did not increase. These results showed that Th1-biased humoral immune responses against WT1 protein were generated in leukemias and MDS. These results should allow us to consider that Th1-biased cellular immune responses against WT1 protein, which was essentially needed for cancer immunotherapy targeting WT1, should be elicited in patients with hematopoietic malignancies.

Antibody Formation↗

Direct action of parathyroid hormone-related peptide to enhance corticosterone production stimulated by adrenocorticotropic hormone in adrenocortical cells of hens.

The presence of receptor for chicken parathyroid hormone-related peptide (cPTHrP) in the cortical cells of the adrenal gland of the hen was demonstrated by radioligand binding assays. When the cortical cells were incubated in vitro with chicken adrenocorticotropic hormone (cACTH) in the presence of cPTHrP, greater production of corticosterone was observed than when incubated with cACTH alone. The results suggest that PTHrP may act directly on the adrenocortical cells via its receptor binding and increase the response to ACTH for corticosterone secretion in the hen.

Adrenal Cortex↗

Analysis of recessive lethality on swine chromosome 6 in a Göttingen miniature resource family.

Previously, we reported recessive gene(s) that terminate fetal development on swine chromosome (SSC) 6 between SW855 and SW122. The affected alleles originated from a Göttingen miniature pig used for construction of a Göttingen miniature pig x Meishan resource population. However, it is not known when the gene(s) are activated during fetal development, which is one of the important factors in selecting candidate genes responsible for fetal death. In the present study, a second swine population consisting of 159 progeny was produced by mating pigs carrying the deleterious allele(s). This population allowed us to narrow the genetic region harbouring the affected gene(s) and to demonstrate that the region was confined between RYR1 and SW782 (5.7 cM on the National Institute of Animal Industry (NIAI) map and 100 cR on the INRA/University of Minnesota porcine radiation hybrid panel map). In order to determine when the affected gene(s) are activated and in turn terminate fetal development, embryos produced in the second population were collected at several development stages and genotyped for markers in the region. Genes in the homozygous state affected embryo development between 9 and 11 days post-coitus.

Animals↗

Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1.

BACKGROUND: Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominantly inherited skin disorders that histologically share the characteristics of suprabasal separation and acantholysis of epidermal keratinocytes. Various mutations in the DD gene (ATP2A2) and the HHD gene (ATP2C1) (respectively encoding the calcium pumps of the sarco/endoplasmic reticulum and the Golgi apparatus) have recently been described in multiple families with DD and HHD. Mutations in ATP2A2 or ATP2C1 have been suggested as causing the conditions via the mechanism of haploinsufficiency. Ultraviolet (UV) B irradiation is thought to be an aggravating factor in both diseases. OBJECTIVES: To examine the effects of various stimuli on ATP2A2 and ATP2C1 mRNA expression, and to examine the role of calcium pumps during keratinocyte differentiation. METHODS: The effects of UVB irradiation, of UVB-inducible inflammatory cytokines produced by keratinocytes and of high-calcium medium (1.8 mmol L(-1) as opposed to 0.08 mmol L(-1) Ca2+) on ATP2A2 and ATP2C1 mRNA expression were quantified in cultured normal human keratinocytes using reverse transcription-polymerase chain reaction. RESULTS: Expression of ATP2A2 and ATP2C1 mRNA was suppressed immediately after exposure to UVB irradiation, and modulation of mRNA expression was achieved in keratinocytes cultured with proinflammatory cytokines. The mRNA expression of both genes was increased significantly after the shift to high extracellular Ca2+ concentration. CONCLUSIONS: The results suggest that modulation of ATP2A2 and ATP2C1 mRNA expression by UV or cytokines might contribute to the clinical presentations unique to DD and HHD, and that the controlled expression of these genes plays an important role in keratinocyte homeostasis, function and differentiation.

Calcium↗

Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes.

BACKGROUND: Darier's disease (DD) and Hailey-Hailey disease (HHD) are skin disorders arising, respectively, from autosomal dominant mutations in ATP2A2, encoding the sacro/endoplasmic reticulum calcium ATPase, and ATP2C1, encoding the Golgi apparatus calcium ATPase. Exposure to ultraviolet (UV) B irradiation exacerbates the skin lesions, which can be treated with corticosteroids and retinoids. OBJECTIVES: To investigate the molecular basis for DD and HHD. METHODS: We used quantitative reverse transcriptase-polymerase chain reactions to examine the effects of UVB irradiation on ATP2A2 and ATP2C1 mRNA levels in cultured normal keratinocytes. RESULTS: We observed that UVB irradiation reduced ATP2A2 and ATP2C mRNA levels. The addition of retinoids or corticosteroids to the cell culture inhibited the UVB-induced suppression of both ATP2A2 and ATP2C1 mRNA levels, and UVB-induced suppression of ATP2C1 mRNA was also inhibited by the addition of ciclosporin, tacrolimus and vitamin D(3). The addition of anti-interleukin (IL)-6 antibody to the cell culture prevented the UVB-induced suppression of ATP2A2 and ATP2C1 mRNA; in contrast, the addition of anti-IL-8 antibody slightly accelerated the suppression. CONCLUSIONS: These results suggest that drugs effective for DD and HHD act by modulating ATP2A2 and ATP2C1 mRNA expression, respectively, and that the proinflammatory cytokines IL-6 and IL-8 play important roles in the regulation of ATPA2 and ATP2C1 expression in homeostasis and/or inflammation of the skin.

Antibodies↗

CDK5 regulates cell-cell and cell-matrix adhesion in human keratinocytes.

BACKGROUND: CDK5 is a member of proline-directed serine/threonine kinases. Although its cDNA was originally cloned as a homologue to those for the other members of the cyclin-dependent kinase (CDK) family, CDK5 has been shown to function differently from other CDKs. CDK5 is activated by non-cyclin partners, p35 and p39, and important during brain development by influencing adhesion, migration and differentiation of neurones. OBJECTIVES: We sought to investigate the expression and functions of CDK5 in human keratinocytes. METHODS: Expression of CDK5/p35, interaction of CDK5/p35 with adhesion molecules, and its roles in cell-cell and cell-matrix adhesion were studied by reverse transcriptase-polymerase chain reaction, immunoblotting and aggregation/adhesion assays in primary cultured normal human keratinocytes from infant foreskins and a human keratinocyte HaCaT cell line. Localization of CDK5 and p35 in normal human epidermis and psoriatic epidermis was studied by immunohistochemistry. RESULTS: Both CDK5 and p35 were expressed in primary cultured keratinocytes, HaCaT cells and normal human epidermis. Roscovitine, an inhibitor of CDK5, enhanced Ca2+-dependent (cadherin-dependent) aggregation of HaCaT cells whereas it inhibited adhesion of HaCaT cells to fibronectin associated with reduced active states of beta1 integrin. Interestingly, psoriatic skin showed reduced CDK5 and p35 expression in the lower half of the epidermis, which might be associated with decreased amount of activated beta1 integrin in the epidermis of psoriatic skin. CONCLUSIONS: CDK5/p35 may be involved in cell-cell and cell-matrix adhesion in human keratinocytes by differently regulating cadherins and integrins. Furthermore, reduced expression of CDK5/p35 in the epidermis might be involved in the pathogenesis of psoriasis.

Calcium↗

A Japanese infant with localized ichthyosis linearis circumflexa on the palms and soles harbouring a compound heterozygous mutation in the SPINK5 gene.

We report a 6-month-old Japanese boy showing ichthyosis linearis circumflexa localized on the palms and soles. He showed bamboo hairs and aminoaciduria, and was positive for cow's milk and egg IgE antibodies by radioallergosorbent tests. Trypsin-like hydrolytic activity in the patient's lesional stratum corneum showed an activity seven times higher than that in age-matched controls. DNA analysis showed that the patient harboured the compound heterozygous mutations R790X and 1220+1 G-->C in the SPINK5 gene, compatible with the diagnosis of Netherton syndrome (NS). As the genotype/phenotype correlations in NS have not yet been fully clarified, the position of the premature termination codon in the SPINK5 gene may contribute to explain such a mild form of NS in our patient.

Asian People↗

The squamous cell carcinoma antigens as relevant biomarkers of atopic dermatitis.

BACKGROUND: Although it is thought that both Th1- and Th2-type inflammations are involved in the pathogenesis of atopic dermatitis (AD), it is controversial which immune response is more involved in regulating the clinical severity of AD. We recently found that the squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 are novel biomarkers of bronchial asthma, downstream of IL-4 and IL-13. OBJECTIVE: We examined whether SCCA1 and SCCA2 could also serve as biomarkers of AD, reflecting its Th2-type immune responses, and whether the expression level of SCCA was correlated with clinical severity of AD. METHOD: We compared the expression of SCCA1 and SCCA2 at the mRNA and protein levels in both involved and uninvolved skin of AD patients and in normal control skin. We next analysed induction of SCCA by IL-4 or IL-13 in keratinocytes. Finally, we compared the serum level of SCCA with laboratory parameters reflecting Th2-type inflammation and clinical severity in AD patients. RESULTS: SCCA1 and SCCA2 were highly expressed in involved skin of AD patients, compared with their uninvolved skin, at both mRNA and protein levels. SCCA protein was dominantly expressed in suprabasal keratinocytes in the epidermis of AD patients. Either IL-4 or IL-13, but not IFN-gamma or TNF, induced production of SCCA in keratinocytes. These result suggest that SCCA is induced in AD skin, probably due to direct actions of IL-4 and/or IL-13 on keratinocytes. Serum levels of SCCA were well correlated with eosinophil numbers and serum lactate dehydrogenase levels, and weakly with serum IgE levels, in AD patients. Furthermore, serum levels of SCCA were strongly correlated with clinical severity. CONCLUSIONS: Th2-type inflammation dominantly regulates the clinical severity of AD, and SCCA is a relevant biomarker of AD, reflecting both Th2-type inflammation and clinical severity.

Adult↗

HLA-haploidentical nonmyeloablative stem cell transplantation: induction to tolerance without passing through mixed chimaerism.

There are few reports of unmanipulated HLA-haploidentical nonmyeloablative stem cell transplantation (NST) using only pharmacological acute graft-vs.-host disease (GVHD) prophylaxis. We present here a successful case of unmanipulated HLA-haploidentical NST for mediastinal large B cell lymphoma that was resistant to autologous peripheral blood stem cell transplantation (PBSCT). The conditioning regimen consisted of fludarabine, busulfan and rabbit anti-T-lymphocyte globulin (ATG) in addition to rituximab. GVHD prophylaxis was performed using tacrolimus and methylprednisolone 1 mg/kg. The patient had rapid engraftment, with 100% donor chimaerism in the lineages of both T cells and granulocytes on day +12, but developed no GVHD clinically. The patient is still in complete remission past day +1020, with no sign of chronic GVHD without receiving immunosuppressive agents. HLA-haploidentical NST may be performed without utilizing mixed chimaerism.

Adult↗

A case of chromomycosis caused by Fonsecaea pedrosoi and a review of reported cases of dematiaceous fungal infection in Japan.

We report a case of chromomycosis caused by Fonsecaea pedrosoi that developed in the left buttock of a 63-year-old female farmer. About 4 years ago, the patient developed erythema in the left buttock, which gradually spread. At the first consultation, we noted a well-defined, red-brown, infiltrated erythematous plaque (8 x 6 cm). Histopathological examination revealed a granulomatous lesion, containing sclerotic cells, associated with giant cells in the upper dermis. The causative fungus was difficult to identify due to low conidiogenesis, but was eventually identified by slide culture as F. pedrosoi. Excision and skin graft were performed, and no recurrence has been observed after 2 years. In Japan, 212 cases of dematiaceous fungal infection were reported in the period from 1982 to 2001. The causative fungus was F. pedrosoi in the majority of cases (126/212; 66%), followed by Exophiala jeanselmei (36/212; 19%). Similar incidence of dematiaceous fungal infection was reported in male and female patients. The upper limbs were affected most frequently in both male and female patients. Ten cases were associated with visceral lesions.

Ascomycota↗

Serum vitamin C-periodontal relationship in community-dwelling elderly Japanese.

OBJECTIVE: To determine the relationship between serum vitamin C and periodontitis as estimated by clinical attachment loss (CAL) in community-dwelling elderly Japanese. MATERIAL AND METHODS: This analysis was confined to 413 Niigata citizens aged 70 years in whom the data for serum vitamin C and CAL were available. High-pressure liquid chromatography method was used to ascertain the serum vitamin C levels while CAL was assessed on six sites of all teeth present including third molars by means of pressure-sensitive probes. Other variables included gender, smoking, toothbrushing frequency, number of teeth present and random blood sugar levels. RESULTS: Serum vitamin C concentration was inversely related to CAL (r=-0.23, p<0.00005) at bivariate level. Multiple linear regression analysis showed that CAL was 4% greater in subjects with lower serum vitamin C levels than in subjects with higher serum vitamin C levels notwithstanding smoking, diabetes, oral hygiene, gender or number of teeth present. CONCLUSION: The findings suggested that serum vitamin C might have relatively weak but a statistically significant relationship with periodontitis in this elderly population.

Aged↗

Relationship between bleeding on probing and periodontal disease progression in community-dwelling older adults.

OBJECTIVE: The main objective of this study was to determine the relationship between bleeding on probing (BOP) and periodontal disease progression in community-dwelling older adults. METHODS: A 3-year longitudinal study was carried out in 229 non-smoking healthy older adults aged 70 years. Using pressure-controlled periodontal probes, BOP, pocket depth and attachment level at 13,289 sites were measured annually. Periodontal disease progression was defined as an increase in attachment loss of >or=3 mm from the baseline to the final examination. The backward stepwise logistic regression analysis was performed to assess the relationship between the total number of sites with BOP in the four examinations and periodontal progression. RESULTS: Logistic regression analysis showed that the odds ratios of BOP frequency for periodontal disease progression ranged from 1.4 to 6.2 after controlling for pocket depth >or=4 mm at baseline, number of missing teeth, jaw type and tooth site. CONCLUSION: Increasing frequencies of bleeding might increase the probability of periodontal disease progression in community-dwelling older adults.

Aged↗