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Biomedical subjects

Masayuki Yamaguchi

Publications and source records attributed to Masayuki Yamaguchi.

15 recordsLinked to original sources

Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.

Since interaction between bone and lipid metabolism has been suggested, this study investigated the regulation of bone metabolism by adiponectin, a representative adipokine, by analyzing deficient and overexpressing transgenic mice. We initially confirmed that adiponectin and its receptors were expressed in osteoblastic and osteoclastic cells, indicating that adiponectin can act on bone not only through an endocrine pathway as a hormone secreted from fat tissue, but also through an autocrine/paracrine pathway. There was no abnormality in bone mass or turnover of adiponectin-deficient (Ad-/-) mice, possibly due to an equivalent balance of the two pathways. In the culture of bone marrow cells from the Ad-/- mice, osteogenesis was decreased compared to the wild-type (WT) cell culture, indicating a positive effect of endogenous adiponectin through the autocrine/paracrine pathway. To examine the endocrine action of adiponectin, we analyzed transgenic mice overexpressing adiponectin in the liver, and found no abnormality in the bone. Addition of recombinant adiponectin in cultured osteoprogenitor cells suppressed osteogenesis, suggesting that the direct action of circulating adiponectin was negative for bone formation. In the presence of insulin, however, this suppression was blunted, and adiponectin enhanced the insulin-induced phosphorylations of the main downstream molecule insulin receptor substrate-1 and Akt. These lines of results suggest three distinct adiponectin actions on bone formation: a positive action through the autocrine/paracrine pathway by locally produced adiponectin, a negative action through the direct pathway by circulating adiponectin, and a positive action through the indirect pathway by circulating adiponectin via enhancement of the insulin signaling.

Adiponectin↗

In vivo localized 1H MR spectroscopy of rat testes: stimulated echo acquisition mode (STEAM) combined with short TI inversion recovery (STIR) improves the detection of metabolite signals.

A noninvasive NMR technique for evaluating testicular function was explored in this study. Localized in vivo 1H NMR spectroscopy was performed on rat testes using a stimulated echo acquisition mode (STEAM) sequence with a short echo time (TE). In the 1H spectra, large lipid signals dominated the chemical shift range of 0.89-2.78 ppm, which prevented the observation of metabolite signals in this region. To suppress these lipid signals, short inversion time (TI) inversion recovery (STIR) was combined with STEAM (STIR-STEAM). The optimal TI was typically 320 ms. STIR-STEAM with a TE of 15 ms allowed successful suppression of the lipid signals and the sensitive detection of several new metabolite signals. In normal testes, choline, creatine, glutamate, and glycine signals were identified. In addition to these metabolites, a lactate signal was observed in ischemic testes. To our knowledge, the signals of glutamate, glycine, and lactate have not been previously assigned in 1H MR spectra of testes in vivo. Lipid suppression by STIR aided in the detection of these metabolites, which would otherwise have been masked by the lipid signals.

Animals↗

Suppression of aging in mice by the hormone Klotho.

A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.

Aging↗

Insulin receptor substrate-1 is required for bone anabolic function of parathyroid hormone in mice.

Bone anabolic action of PTH has been suggested to be mediated by induction of IGF-I in osteoblasts; however, little is known about the molecular mechanism by which IGF-I leads to bone formation under the PTH stimulation. This study initially confirmed in mouse osteoblast cultures that PTH treatment increased IGF-I mRNA and protein levels and alkaline phosphatase activity, which were accompanied by phosphorylations of IGF-I receptor, insulin receptor substrate (IRS)-1 and IRS-2, essential adaptor molecules for the IGF-I signaling. To learn the involvement of IRS-1 and IRS-2 in the bone anabolic action of PTH in vivo, IRS-1-/- and IRS-2-/- mice and their respective wild-type littermates were given daily injections of PTH (80 mug/kg) or vehicle for 4 wk. In the wild-type mice, the PTH injection increased bone mineral densities of the femur, tibia, and vertebrae by 10-20% without altering the serum IGF-I level. These stimulations were similarly seen in IRS-2-/- mice; however, they were markedly suppressed in IRS-1-/- mice. Although the PTH anabolic effects were stronger on trabecular bones than on cortical bones, the stimulations on both bones were blocked in IRS-1-/- mice but not in IRS-2-/- mice. Histomorphometric and biochemical analyses showed an increased bone turnover by PTH, which was also blunted by the IRS-1 deficiency, though not by the IRS-2 deficiency. These results indicate that the PTH bone anabolic action is mediated by the activation of IRS-1, but not IRS-2, as a downstream signaling of IGF-I that acts locally as an autocrine/paracrine factor.

Animals↗

Quantitative assessment of the hepatic pharmacokinetics of the antimicrobial sitafloxacin in humans using in vivoF magnetic resonance spectroscopy.

AIMS: To measure hepatic concentrations of the fluorine-containing antimicrobial, sitafloxacin, using in vivo(19)F magnetic resonance spectroscopy (MRS). METHODS: Data were acquired from eight healthy subjects at 2, 5, 8 and 24 h following doses of 500 mg day(-1) for 5 days using a (1)H/(19)F surface coil in a 1.5T clinical MR system. Tissue water was used as a reference. RESULTS: Estimated liver concentrations at 2 h were 15.0 +/- 4.0 microg ml(-1) (mean +/- 95% CI), compared with 3.54 +/- 0.58 microg ml(-1) in plasma (n = 6), and fell below threshold concentrations (2 microg ml(-1)) by 24 h. CONCLUSIONS: (19)F MRS is able to detect and quantify sitafloxacin in the liver. There was no evidence for the hepatic retention of the drug.

Adolescent↗

Triple arterial phase dynamic MRI with sensitivity encoding for hypervascular hepatocellular carcinoma: comparison of the diagnostic accuracy among the early, middle, late, and whole triple arterial phase imaging.

OBJECTIVE: We assessed and compared the diagnostic accuracy of the early, middle, late, and whole triple arterial phase MRI with sensitivity encoding (SENSE) for the detection of hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirty-one patients with 102 HCCs underwent dynamic MRI with SENSE. The findings of CT examinations, combined with those of visceral angiography or histopathologic examination, were used as the gold standard. After acquisition of T1- and T2-weighted images, gadolinium-enhanced triple arterial, portal, and delayed phase images were obtained. Acquisition of the triple arterial phase imaging was started at the timing of peak aortic enhancement and completed within a single breath-hold. Acquisition time for each phase was 8.4 sec. Four image sets including the early, middle, late, and whole triple arterial phase imaging were interpreted separately by four observers. The mean values of area under alternative-free-response receiver operating characteristic (AFROC) curve and of sensitivity were compared among the four image sets. RESULTS: The mean values of area under AFROC curve were 0.52, 0.66, 0.53, and 0.68 and of sensitivity were 45%, 64%, 48%, and 65% for the image sets with the early, middle, late, and whole triple arterial phase imaging, respectively. Both mean values were significantly higher for the image sets with the middle and whole triple arterial phase imaging than for those with the early and late arterial phase imaging. CONCLUSION: The middle arterial phase imaging with k-space centered at 12.6 sec after the peak aortic enhancement was optimal for detecting HCC and showed diagnostic accuracy equivalent to that of the whole triple arterial phase imaging.

Aged↗

Dual double arterial phase dynamic MR imaging with sensitivity encoding (SENSE): which is better for diagnosing hypervascular hepatocellular carcinomas, in-phase or opposed-phase imaging?

The purpose of this study was to investigate the efficacy of sensitivity encoding (SENSE) dynamic magnetic resonance imaging (MRI) with the dual (in-phase and opposed-phase) double arterial phase to detect hypervascular hepatocellular carcinomas (HCCs). MR images of the liver from 44 consecutive patients were obtained. Dynamic MRI with SENSE was performed six times (precontrast, early arterial, late arterial, 1 min, 3 min and 5 min after contrast injection) at 11 s per scan using the gradient recalled echo sequence (TR/TE/flip angle = 168/2.3 and 4.6/70). In-phase and opposed-phase images were obtained simultaneously each scan. For the quantitative analysis, the signal-to-noise ratio (S/N) of HCC and tumor-to-liver contrast-to-noise ratio (C/N) were analyzed for 55 HCCs. The mean S/N of HCCs on in-phase images showed significantly higher values than that on opposed-phase images regarding all phases (P < 0.001). In arterial phases, the mean tumor-to-liver C/N for in-phase images was significantly higher than that for opposed-phase images (P < 0.05). In portal and delayed-phase images, the mean tumor-to-liver C/N in opposed-phase images showed a negative value. In six HCCs with fatty metamorphosis, the mean tumor-to-liver C/N on arterial phase images approached zero in opposed-phase, while it showed a positive value in-phase. In dual double arterial phase dynamic MRI of the liver, in-phase images were superior to opposed-phase images for detecting early enhancement of hypervascular HCCs, while the latter were superior for detecting washout of contrast media from HCCs in the portal and delayed phase. The combination of both images overcomes the difficulty of diagnosing hypervascular HCCs with fatty metamorphosis.

Aged↗

PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors.

Based on the fact that aging is associated with a reciprocal decrease of osteogenesis and an increase of adipogenesis in bone marrow and that osteoblasts and adipocytes share a common progenitor, this study investigated the role of PPARgamma, a key regulator of adipocyte differentiation, in bone metabolism. Homozygous PPARgamma-deficient ES cells failed to differentiate into adipocytes, but spontaneously differentiated into osteoblasts, and these were restored by reintroduction of the PPARgamma gene. Heterozygous PPARgamma-deficient mice exhibited high bone mass with increased osteoblastogenesis, but normal osteoblast and osteoclast functions, and this effect was not mediated by insulin or leptin. The osteogenic effect of PPARgamma haploinsufficiency became prominent with aging but was not changed upon ovariectomy. The PPARgamma haploinsufficiency was confirmed to enhance osteoblastogenesis in the bone marrow cell culture but did not affect the cultures of differentiated osteoblasts or osteoclast-lineage cells. This study demonstrates a PPARgamma-dependent regulation of bone metabolism in vivo, in that PPARgamma insufficiency increases bone mass by stimulating osteoblastogenesis from bone marrow progenitors.

Animals↗

[Clinical study and treatment of uterine sarcoma at Niigata City General Hospital].

We report a retrospective study of 16 patients with uterine sarcoma from 1986 to 2001 in Niigata City General Hospital. Five-year survival rates in stage I, II, III and IV (FIGO) were 68% (n = 4), 50% (n = 2), 0% (n = 3), and 0% (n = 7), respectively. Overall survival for the patients with incomplete resection of tumor at primary laparotomy (n = 7) was significantly poorer than that with complete resection (n = 8). Patients with a high-LDH (lactic acid dehydrogenase) value tended to have poorer prognoses, but there was no significant difference of overall survival between the high-LDH group (n = 8) and the normal-LDH group (n = 8). Fifteen patients had postsurgical adjuvant chemotherapy. Out of 5 evaluable patients undergoing first-line chemotherapy, there were only 2 partial responders with IAP (ifosfamide, adriamycin, cisplatin) chemotherapy, and out of 11 evaluable patients undergoing second-line chemotherapy, there was only 1 partial responder with IAP. Out of 10 patients who had no evidence of disease after prior therapy, 6 patients had recurrences. Five patients underwent secondary surgery for recurrence and residual tumor. Of them, 3 patients did not have complete resection of residual tumor and died within 1 year after secondary surgery. Although prognosis of advanced uterine sarcoma and recurrence is poor, it is suggested that aggressive resection for recurrence and residual tumor improves prognosis.

Adult↗

Accelerated dynamic MR imaging with a parallel imaging technique for hypervascular hepatocellular carcinomas: usefulness of a test bolus in examination and subtraction imaging.

PURPOSE: To assess the impact of the accelerated dynamic MR imaging (ADMRI) approach using parallel imaging for detecting hypervascular hepatocellular carcinomas (HCCs) and to evaluate the usefulness of a test bolus in examination and subtraction imaging in this setting. MATERIALS AND METHODS: Thirty patients with 135 HCCs underwent ADMRI using a two-dimensional gradient-recalled echo sequence with parallel imaging. Seventeen patients were evaluated without a test bolus and 13 patients with a test bolus. The detectability of HCCs was calculated between the groups with and without a test bolus. ADMRI was evaluated regarding the signal-to-noise ratio (SNR) of the lesion and the liver, the contrast-to-noise ratio (CNR) of the lesion vs. the liver, and the feasibility of subtraction images. RESULTS: ADMRI with and without a test bolus had almost equal sensitivity (92.5% and 92.6%). No significant difference was seen in the SNR of lesions and the CNR of lesions vs. livers between both groups. With a test bolus, ADMRI could depict the peak enhancement of nodules on the 2nd or 3rd dynamic phases and optimized the timing of peak lesion enhancement. Subtraction images could be obtained regarding minimal slice misregistration. CONCLUSION: ADMRI had high detectability of HCCs with and without a test bolus.

Adult↗

Double arterial phase dynamic MRI with sensitivity encoding (SENSE) for hypervascular hepatocellular carcinomas.

PURPOSE: To investigate the efficacy of SENSE MRI, including the double arterial phase dynamic study, to detect hypervascular hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: MRI of the liver was performed in 40 consecutive patients (20 by conventional MRI and 20 by SENSE MRI). The SENSE technique was used to obtain breath-hold T1-weighted FSE images (TR/TE = 556/12 msec), respiratory-triggered T2-weighted FSE images (TR/TE = 1800/90 msec) with and without fat suppression, and dynamic MR images (TR/TE/FA = 160-168/4.6 msec/70 degrees ). In each arterial dominant phase and portal dominant phase, two scans were consecutively performed with one breath-hold, leading to the double arterial phase and double portal phase images with SENSE. RESULTS: The sensitivity of SENSE MRI for HCCs diagnosed from all MR images, including dynamic study, T1-weighted images, and T2-weighted images, was 91.7%, while that of conventional MRI was 76.3%. The positive predictive value of SENSE MRI for HCCs was 91.7%, while that of conventional MRI was 87.9%. In terms of HCCs < or = 10 mm, the sensitivity and positive predictive values of SENSE MRI were 78.6% and 78.6%, respectively, while those of conventional MRI were 27.3% and 60.0%, respectively. The number of detected HCCs < or = 10 mm was significantly larger in SENSE MRI than in conventional MRI (P < 0.05). The cause of false-positive lesions on SENSE MR images was an arterioportal shunt. CONCLUSION: SENSE MRI with double arterial phase dynamic study showed higher sensitivity compared to the conventional technique. Therefore, SENSE MRI is a promising method for the detection of HCC.

Carcinoma, Hepatocellular↗

Splenic artery aneurysm of the anomalous splenomesenteric trunk: successful treatment by transcatheter embolization using detachable coils.

A splenomesenteric trunk, which involves replacing the splenic artery from the superior mesenteric artery (SMA), is rare and occurs in less than 1% of patients. We report a case of an aneurysm involving the origin of the splenic artery that anomalously arose from the SMA, and which was successfully treated using Guglielmi detachable coils.

Aneurysm↗

Contrast-enhanced CT with saline flush technique using two automated injectors: how much contrast medium does it save?

PURPOSE: The purpose of this work was to investigate the volume of contrast medium saved by the saline flush technique. METHOD: Thoracic helical CT was performed by injecting 75 ml of contrast material (Ioversol 320) only (n = 25; Group A) or 75 ml of contrast medium pushed with 6 ml (n = 25; Group B), 12 ml (n = 25; Group C), 25 ml (n = 25; Group D), or 50 ml (n = 25; Group E) of saline at a rate of 2 ml/s. The aortic CT numbers were measured from 30 to 55 s after the beginning of injection. We compared the time to peak aortic enhancement (TPAE) among Groups A-E. RESULTS: The TPAEs of the Groups A-E were 42.6, 45.2, 48.6, 48.4, and 48.3 s, respectively, and there was a statistically significant difference among them (p < 0.0001, analysis of variance). Post hoc test revealed statistically significant differences in TPAE between Groups A and B, C, D, and E and between Groups B and C, D, and E but no differences among Groups C, D, and E. CONCLUSION: The saline flush technique prolongs TPAE by 6 s and saves 12 ml of contrast medium.

Adult↗