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Biomedical subjects

M Takata

Publications and source records attributed to M Takata.

At least 19 recordsLinked to original sources

Specific detection of prion antigenic determinants retained in bovine meat and bone meal by flow microbead immunoassay.

AIMS: The purpose of this study was to develop an effective method for detecting prion (PrP) antigenic determinants remaining in bovine meat and bone meal (MBM) using pressurized fluid extraction (PSE) equipment and flow microbead immunoassay (FMI). METHODS AND RESULTS: Using the FMI, bovine recombinant PrP could be determined quantitatively in the 7 pmol-7 nmol range using anti-PrP peptide polyclonal antibody-coupled microbeads and anti-PrP monoclonal antibody (SAF61) as a detection antibody. PSE extraction at 120 degrees C for 5 min under high pressure was most effective for eluting PrP determinants from bovine MBMs. The FMI was capable of detecting PrP determinants in bovine MBM extracts with high specificity and indicated that the MBMs contained high levels of PrP determinants. This assay was also applied to the detection of PrP(Sc) determinants in bovine MBM spiked with a scrapie-infected brain at a weight ratio of 50 : 1. CONCLUSIONS: These data indicate that this assay was effective for the specific detection of PrP determinants contained in bovine MBM extracts. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report detailing the detection of PrP determinants in bovine MBM. The assay could be applied to securing the safety of bovine MBM.

Animal Feed↗

[Right atrial blood cyst; report of a case].

A 53-year-old female was admitted to our hospital for examination of an abnormal shadow on chest X-ray. Computed tomography (CT) revealed a large mass of 3 cm in diameter in the right atrium. The mass arose from the right atrial septum and was removed with the interatrial septum. Histological specimen showed a blood cyst contained serous effusion.

Cysts↗

Magnetic-field switching of crystal structure in an orbital-spin-coupled system: MnV2O4.

We studied the magnetic and structural properties of spinel MnV2O4, which has S=5/2 spin with no orbital degrees of freedom on the Mn2+ site and S=1 spin and three orbital degrees of freedom on the V3+ site. We found that the ferrimagnetic ordering at TN=56.5K and the structural phase transition at Ts=53.5K are closely correlated in this compound and found a switching of crystal structure between cubic and tetragonal phases by the magnetic field. This phenomenon can be explained by the coupling between orbital and spin degrees of freedom in the t2g states of the V site.

Journal Article↗

Keratinocyte growth factor therapy in murine oleic acid-induced acute lung injury.

Alveolar type II (ATII) cell proliferation and differentiation are important mechanisms in repair following injury to the alveolar epithelium. KGF is a potent ATII cell mitogen, which has been demonstrated to be protective in a number of animal models of lung injury. We have assessed the effect of recombinant human KGF (rhKGF) and liposome-mediated KGF gene delivery in vivo and evaluated the potential of KGF as a therapy for acute lung injury in mice. rhKGF was administered intratracheally in male BALB/c mice to assess dose response and time course of proliferation. SP-B immunohistochemistry demonstrated significant increases in ATII cell numbers at all rhKGF doses compared with control animals and peaked 2 days following administration of 10 mg/kg rhKGF. Protein therapy in general is very expensive, and gene therapy has been suggested as a cheaper alternative for many protein replacement therapies. We evaluated the effect of topical and systemic liposome-mediated KGF-gene delivery on ATII cell proliferation. SP-B immunohistochemistry showed only modest increases in ATII cell numbers following gene delivery, and these approaches were therefore not believed to be capable of reaching therapeutic levels. The effect of rhKGF was evaluated in a murine model of OA-induced lung injury. This model was found to be associated with significant alveolar damage leading to severe impairment of gas exchange and lung compliance. Pretreatment with rhKGF 2 days before intravenous OA challenge resulted in significant improvements in PO2, PCO2, and lung compliance. This study suggests the feasibility of KGF as a therapy for acute lung injury.

Acute Disease↗

PGE1 inhibits the expression of PAI-1 mRNA induced by TNF-alpha in human mesangial cells.

We examined the effect of PGE1 on the expression of plasminogen activator inhibitor-1 (PAI-1) mRNA induced by tumor necrosis factor-alpha (TNF-alpha) in human mesangial cells, because PAI-1 is one of major factors for the progression of glomerulosclerosis. The expression of PAI-1 mRNA was increased after stimulation with TNF-alpha, and it was diminished by pre-incubation with PGE1. Next, we examined the effect of PGE1 on the phosphorylation of mitogen activated protein kinase (MAPK) family and Akt. TNF-alpha activated the phosphorylation of p44/42 MAPK, p38 MAPK, SAPK/JNK and Akt in mesangial cells. PGE1 inhibited the TNF-alpha induced phosphorylation of SAPK/JNK and Akt, but not p44/42 MAPK and p38 MAPK. The TNF-alpha induced expression of PAI-1 mRNA was not affected by PD98059, an inhibitor of MEK, SB203580, an inhibitor of p38 MAPK, nor LY294002, an inhibitor of PI3 K. However, DMAP, an inhibitor of SAPK/JNK, inhibited the expression of PAI-1 mRNA, suggesting that the TNF-alpha induced expression of PAI-1 mRNA is regulated by the SAPK/JNK dependent pathway in human mesangial cells. By the incubation with H8, an inhibitor of PKA, the inhibitory effect of PGE1 on the expression of PAI-1 mRNA was abolished, suggesting that PGE1 inhibited the PAI-1 mRNA expression via the PKA pathway. Our results suggest that the inhibition of PAI-1 synthesis by PGE1 in human mesangial cells may have therapeutic implications for glomerulosclerosis such as occurs in diabetic nephropathy.

Alprostadil↗

Relationship of lipoprotein lipase and hepatic triacylglycerol lipase activity to serum adiponectin levels in Japanese hyperlipidemic men.

OBJECTIVE: The aim of this study was to determine how lipoprotein lipase (LPL) and hepatic triacylglycerol lipase (HTGL) activity relate to serum adiponectin levels. RESEARCH DESIGN AND METHODS: Fifty-five hyperlipidemic Japanese men were recruited for this study. LPL and HTGL activity in post-heparin plasma (PHP) was measured using Triton X-100 emulsified-[14C] triolein. The remaining activity in the presence of 1M NaCl was defined as HTGL activity. Serum adiponectin levels were determined by an enzyme-linked immunosorbent assay system. RESULT: LPL activity had a positive relationship with HDL2, but had no relation with HDL3, while HTGL had positive relationship with HDL3, but had no relationship with HDL2. LPL activity showed a positive relationship [r = 0.345, p = 0.010] to serum adiponectin levels, while and HTGL activity showed an inverse relationship [r = - 0.365 p = 0.006]. Multiple regression analysis with LPL and HTGL as dependent variables and age, BMI, serum adiponectin and the homeostasis model assessment of insulin resistance (HOMA-IR) as independent variables showed LPL and HTGL's association to adiponectin did not persist after adjustments for these covariants. However, the association of LPL activity to HOMA-IR was found to persist after adjustments of age, BMI, and serum adiponectin. CONCLUSIONS: There was a co-linearity between insulin sensitivity and adiponectin as well as insulin sensitivity and LPL/HTGL activity.

Aged↗

Abnormal renal structural alterations during the development of diabetes mellitus in Otsuka Long-Evans Tokushima Fatty rats.

AIM: The aim of this study was to investigate the renal structural properties in diabetic nephropathy. METHODS: Flow-pressure and pressure-glomerular filtration rate (GFR) relationships were determined for maximally vasodilated kidneys at 10 (pre-diabetic stage) and 42 weeks of age (diabetic stage) in Otsuka Long-Evans Tokushima Fatty rats (OLETF), an animal model of type 2 diabetes mellitus, using age-matched Long-Evans Tokushima Otsuka rats (LETO) as non-diabetic controls (n = 9 of each age for each strain). Kidneys were then perfusion-fixed for histological analysis. RESULTS: At 10 weeks of age, the slope of flow-pressure relationship (minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature) was steeper in OLETF than in LETO. In contrast, the threshold pressure for beginning filtration (preglomerular-to-postglomerular vascular resistance ratio) at pressure-GFR relationship did not differ between the two strains; however, the slope of the relationship (glomerular filtration capacity) was lower in OLETF than in LETO. Thus, in the kidneys of 10-week-old OLETF rats, vascular narrowing and impaired glomerular filtration capacity already existed with no abnormalities in preglomerular-to-postglomerular vascular resistance ratio. From the age of 10-42 weeks, the following results were obtained: (1) Minimal renal vascular resistance decreased in both strains, but it diminished markedly in OLETF. (2) The pressure for beginning filtration increased in LETO, but remained unchanged in OLETF. (3) Glomerular filtration capacity decreased to the similar extent in both strains. (4) Histologically, the vascular lumen and wall thickness increased in the interlobular arteries of both strains. However, vascular luminal widening was more pronounced in OLETF, resulting in the reduction in wall to lumen ratio. (5) Glomerular injuries and increased blood pressure occurred only in OLETF. CONCLUSION: In conclusion, during progression from the prediabetic to diabetic stage of OLETF, the pre-existing vascular narrowing was markedly attenuated without the concomitant increase in preglomerular-to-postglomerular vascular resistance ratio. Combined with increased blood pressure, these renal structural alterations could lead to the elevation of intraglomerular pressure in OLETF.

Animals↗

High-resolution record of Northern Hemisphere climate extending into the last interglacial period.

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.

Journal Article↗

Recombination repair pathway in the maintenance of chromosomal integrity against DNA interstrand crosslinks.

DNA interstrand crosslinks (ICL) present a major threat to cell viability and genome integrity. In eukaryotic cells, the ICLs have been suggested to be repaired by a complex process involving Xpf/Ercc1-mediated endonucleolytic incision and homologous recombination (HR). However, the entire feature of the ICL tolerating mechanism is still poorly understood. Here we studied chromosome aberrations (CA) and sister chromatid exchanges (SCE) by the use of the crosslinking agent mitomycin C (MMC), in chicken DT40 cells with the HR genes disrupted by targeted replacement. The disruption of the Rad54, Rad51B, Rad51C, Rad51D, Xrcc2 and Xrcc3 genes resulted in a dramatic reduction of spontaneous and MMC-induced SCEs. Interestingly, while HR-deficient cells were hypersensitive to cell killing by MMC, MMC-induced CAs were also suppressed in the HR-deficient cells except for Rad51D-, Xrcc2- and Xrcc3-deficient cells. These observations indicate that DNA double strand breaks (DSB) at stalled replication forks and those arising as repair intermediates present strong signals to cell death but can be tolerated by the HR repair pathway, where Rad54, Rad51B and Rad51C have an initiative role and repair can be completed by their paralogs Rad51D, Xrcc2 and Xrcc3. The impairment of the HR pathway, which otherwise leads to cell death, may be somewhat substituted by an alternative mechanism such as the Mre11/Rad50/Nbs1 pathway, resulting in reduced frequencies of SCEs and CAs.

Animals↗

Direct observation of charge transfer in double-perovskite-like RbMn[Fe(CN)6].

The charge density distribution has been determined for a transition metal cyanide, RbMn[Fe(CN)(6)], by means of the maximum entropy-Rietveld method combined with the highly angularly resolved synchrotron radiation x-ray powder diffraction at SPring-8 BL02B2. We directly observed a charge transfer from the Mn site to the Fe site in the low-temperature phase. On the basis of a local density approximation calculation, we discuss the origin for the anisotropic bonding electron distribution around the Mn3+ ion in the low-temperature phase.

Journal Article↗

Charge ordering and spin frustration in AlV2-x CrxO4.

The relationship between charge and spin degrees of freedom in a geometrically frustrated system, AlV2-xCrxO4 spinel, is investigated. Upon Cr doping, the charge-ordered phase of AlV2O4 is rapidly suppressed and a charge-disordered phase grows up instead. It is found that the magnetic ground state is a spin-glass state dominated by geometrical frustration for both phases, but larger spin entropy remains down to low temperatures in the charge-ordered phase, possibly owing to its two-dimensional character.

Journal Article↗

Coexistence of micrometastatic melanoma cells and sarcoid granulomas in all regional lymph nodes in a patient with acral melanoma.

A 68-year-old woman who had been diagnosed with sarcoidosis presented with acral lentiginous melanoma (Breslow's tumour thickness, 2.6 mm; Clark's level IV) on her right heel. She underwent surgery for excision of the primary tumour and sentinel lymph node biopsy. The two sentinel lymph nodes revealed numerous sarcoidal granulomas and small nests of metastatic melanoma cells in the subcapuslar lesions. She subsequently underwent ilio-inguinal lymph node dissection. Surprisingly, all of the nine dissected nodes were mostly replaced by sarcoidal granulomas and contained melanoma micrometastases.

Aged↗

Phenotypic alteration in malignant transformation of colonic villous tumours: with special reference to a comparison with tubular tumours.

AIMS: To clarify the cellular differentiation of colorectal villous tumours in malignant transformation, compared with that of tubular tumours (tubular adenoma and adenocarcinoma arising in tubular adenoma). METHODS AND RESULTS: Forty-nine cases of colorectal villous tumours [six cases of low-grade villous adenoma, 21 of high-grade villous adenoma (VA), nine of invasive carcinoma in villous adenoma (CIVA), and 13 of pure villous carcinoma (PVC)] and 46 cases of tubular tumours [14 cases of low-grade and 17 of high-grade tubular adenoma (TA), and 15 cases of carcinoma in tubular adenoma (CITA)] were selected for this study based on their expression patterns of CD10 (small intestinal brush border), MUC2 (intestinal goblet cell), and HGM (gastric foveolar epithelium). HGM was more frequently expressed in the adenomatous components of villous tumours (63%) than in those of tubular tumours (14%) (P < 0.05). CD10 expression of high-grade TAs (47%) and carcinomas arising in TA (60%) was significantly higher than that of villous tumours (0%) (P < 0.05). CONCLUSIONS: There were significant differences in the phenotypic expression of adenoma and adenocarcinoma between villous and tubular tumours, respectively. Villous tumours have a pathway of malignant transformation different from that of tubular tumours. Because of biological differences, colorectal villous tumours should be distinguished from tubular neoplasia. The analysis of the phenotype of colorectal neoplasms is useful for the evaluation of tumour progression.

Adenocarcinoma↗

Epstein-Barr virus-associated T-cell lymphoma: a case of eyelid swelling and intramuscular infiltration mimicking dermatomyositis.

Association with Epstein-Barr virus (EBV) infection has been noted in various types of cutaneous lymphoproliferative disorders. We report a 57-year-old Japanese woman with T-cell lymphoma mimicking dermatomyositis that was associated with chronic active EBV infection. She presented with low-grade fever, bilateral erythematous swellings on the eyelids, and necrotic papules on the face. Serum creatine kinase levels were elevated and a diffuse reticular shadow was detected in both lung fields. The infiltrate of atypical lymphocytes found in skin and muscle, which contained EBV-encoded small nuclear RNA-1 and EBV, was also detected in the CD4+ peripheral blood cells. Treatment with prednisolone resolved her lesions with no relapse for 3 years, after which there was a recurrence in her left lung. Combination chemotherapy was not effective against the lung lesion and she died with multiple organ failure 2 months after the recurrence.

Dermatomyositis↗

alpha-Tocopherol Inhibits IL-8 synthesis induced by thrombin and high glucose in endothelial cells.

It has been reported that alpha-tocopherol, an antioxidant agent, may play a role in preventing diabetic angiopathy. However, there is little evidence to show the effect of alpha-tocopherol on the production of pro-inflammatory cytokines in endothelial cells. Therefore, we examined the effect of alpha-tocopherol on the regulation of IL-8 synthesis induced by high glucose and/or thrombin in endothelial cells. Thrombin alone markedly increased the IL-8 release. Furthermore, high glucose levels and thrombin combined had additive effects on IL-8 synthesis, and alpha-tocopherol diminished their effect; alpha-tocopherol also inhibited the phosphorylation of IkappaB-alpha induced by high glucose levels and/or thrombin. Our results suggest that the administration of alpha-tocopherol to diabetic patients may have a beneficial effect for the prevention of diabetic vascular complications by the inhibition of IL-8 synthesis from endothelial cells.

Aorta↗

Evaluation of 5-S-cysteinyldopa as a marker of melanoma progression: 10 years' experience.

5-S-Cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. In this study, we measured serum levels of 5-S-CD in 2648 samples taken from 218 patients in order to evaluate the usefulness of this parameter in following melanoma progression and prognosis. 5-S-CD levels were significantly elevated above the upper limit of the normal range (10 nmol/l) in stage IV melanoma patients. The sensitivity of elevated serum 5-S-CD levels in detecting distant metastasis was 73%, while the specificity was 98% and the positive predictive value 94%. The sensitivity was improved to 77% when cases of amelanotic melanoma were excluded. Patients without metastases had elevated 5-S-CD values in 5% of the 1480 serum samples. Changes in serum 5-S-CD levels were followed during disease progression until the end stage in 49 patients. In 33% of the patients, elevation of serum 5-S-CD levels preceded clinical detection of visceral metastases, and in 37% elevation of 5-S-CD levels occurred at the same time as visceral metastasis. Patients with elevated 5-S-CD levels before or after surgical treatment had significantly shorter survival times than those with normal levels. These results show that the level of 5-S-CD in the serum is a sensitive and specific marker in predicting distant metastases. Elevated serum levels of 5-S-CD, before or after surgical treatment, is associated with a poor prognosis.

Adolescent↗

Melanoma inhibitory activity (MIA) as a serum marker for early detection of post-surgical relapse in melanoma patients: comparison with 5-S-cysteinyldopa.

One of the principal applications of tumour markers is the early detection of recurrent disease in the follow-up of patients. In the study described here, we compared the usefulness of two serum markers for melanoma, 5-S-cysteinyldopa (5-S-CD) and melanoma inhibitory activity (MIA), in the monitoring of postsurgical melanoma patients. A total of 154 serum samples taken from 45 melanoma patients, who underwent surgery of the primary tumour and were under periodical follow-up for 13 to 180 months, were analysed. Serum MIA measurements were performed using an enzyme-linked immunosorbent assay (ELISA), and 5-S-CD levels were determined using high performance liquid chromatography (HPLC). In 72 serum samples taken from a group of 31 non-progressive patients with a median follow-up of 48.5 months, false positive rates of both markers were equally low, being 6.9% (five out of 72) for 5-S-CD and 8.3% (six out of 72) for MIA. In contrast, the sensitivity of MIA at the time point of the first clinical relapse in 14 progressive patients was significantly greater than that of 5-S-CD (0.64 [nine out of 14] versus 0.21 [three out of 14]; P < 0.05). Furthermore, seven patients showed abnormal serum MIA values 4-53 months prior to the clinical detection of metastasis, and the elevated levels were often noted on multiple occasions. These results show that MIA was superior to 5-S-CD in monitoring melanoma patients under periodical follow-up after the primary surgery. Repeated elevation of serum MIA levels may predict the presence of clinically undetectable occult metastases, which warrants further prospective investigations to assess the prognostic significance of serum MIA levels in postsurgical melanoma patients.

Aged↗