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Biomedical subjects

Hitoshi Goto

Publications and source records attributed to Hitoshi Goto.

At least 19 recordsLinked to original sources
PubMed2006

The elevated level of circulating matrix metalloproteinase-9 in patients with abdominal aortic aneurysms decreased to levels equal to those of healthy controls after an aortic repair.

Matrix metalloproteinase-9 (MMP-9) is abundantly expressed in abdominal aortic aneurysms (AAAs), and it is considered to play a pivotal role in aneurysmal formation. Elevated circulating concentrations of MMP-9 have been reported in patients with AAA, but the influence of an operation on circulating MMP-9 is unclear. Therefore, to clarify the influence of an operation on circulating MMP-9 levels and to determine the role of MMP-9 in the progression of AAA, we measured serum MMP-9 levels in patients before and after AAA repair. Blood samples were obtained from 53 patients with AAA; 22 patients underwent AAA operations, including 17 patients with arterial occlusive disease (AOD), and nine normal control subjects. Serum MMP-9 levels were determined by an enzyme-linked immunosorbent assay. The serum MMP-9 concentration was significantly higher in AAA patients (622.0 +/- 400.2 ng/mL) than in either AOD patients (284.3 +/- 151.4 ng/mL) or healthy controls (280.8 +/- 165.5 ng/mL) (p < 0.001). The mean serum MMP-9 levels in patients undergoing surgery for AAA (268.1 +/- 215.9 ng/mL) was significantly lower than that in AAA patients (p < 0.01). Among the 10 patients whose sera were obtained preoperatively and postoperatively, the serum MMP-9 concentration fell significantly after the patients underwent the operation (p = 0.004). No significant difference was identified in serum MMP-9 concentrations among AOD patients, controls, and postoperative patients. These studies suggest that MMP-9 plays a pivotal role in aneurysm formation, and the circulating MMP-9 level is thus considered to reflect the biological behavior of the aneurysm.

Aged↗
PubMed2006

Volar dislocation of the extensor carpi ulnaris tendon on magnetic resonance imaging is associated with extensor digitorum communis tendon rupture in rheumatoid wrists.

PURPOSE: Extensor tendon rupture in rheumatoid wrists is a common problem and causes immediate dysfunction of the digits. The best treatment for tendon rupture may be prophylactic management, although the factors associated with tendon rupture must first be identified. The purpose of this study was to evaluate structures around rheumatoid wrists using magnetic resonance imaging with forearm rotation and to identify factors associated with extensor tendon rupture as indications for prophylactic surgery. METHODS: The subjects were 34 patients (40 wrists) with active rheumatoid arthritis. The extensor digitorum communis (EDC) tendons were ruptured in 15 wrists. Magnetic resonance imaging of the wrists was performed in maximally pronated and supinated positions of the forearm. Axial images of the distal radioulnar joints (DRUJs) were selected to evaluate DRUJ synovitis, dorsal tenosynovitis, volar dislocation of the extensor carpi ulnaris (ECU) tendon, sigmoid notch angle, and the radioulnar ratio (RUR) (ie, the degree of DRUJ subluxation). RESULTS: No significant correlations were found between EDC tendon rupture and DRUJ synovitis, dorsal tenosynovitis, or RUR in pronation. Extensor digitorum communis tendon rupture correlated significantly with volar ECU tendon dislocation, sigmoid notch angle, and RUR in supination. Radioulnar ratio correlated significantly with volar ECU tendon dislocation only in supination and not in pronation. Thus, DRUJ subluxation was advanced even in the supinated wrist with volar ECU tendon dislocation. As a factor associated with EDC tendon rupture, volar ECU tendon dislocation had 87% sensitivity and 76% specificity. CONCLUSIONS: Volar ECU tendon dislocation is associated with increased RUR in supination and EDC tendon rupture. Volar ECU tendon dislocation can thus be considered a factor associated with EDC tendon rupture, and its presence may indicate the need for prophylactic surgical intervention in a subset of rheumatoid arthritis patients.

Adolescent↗
PubMed2006

Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism.

OBJECTIVE: While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT)-PCR and immunohistochemistry. RESULTS: FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23. CONCLUSIONS: Serum calcium may regulate circulating FGF-23 levels in PHPT.

Calcium↗
PubMed2006

Paraarticular trabecular bone loss at the ultradistal radius and increased arterial stiffening in postmenopausal patients with rheumatoid arthritis.

OBJECTIVE: We recently reported enhanced arterial thickening in patients with rheumatoid arthritis (RA) and the importance of increased bone resorption in this process. Our aim was to examine whether arterial stiffening, another aspect of atherosclerosis, is also increased in patients with RA, and to determine if it is an important risk factor. METHODS: The subjects were 47 patients with RA and 49 healthy controls, all postmenopausal women. Subjects having risk factors for atherosclerosis were excluded. Femoral-ankle (fa) pulse wave velocity (PWV) and brachial-ankle (ba) PWV were measured in all patients using a waveform analyzer. Bone mineral density (BMD) at the ultradistal radius was assessed by peripheral quantitative computed tomography. Inflammation markers (C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, platelet count) and bone resorption markers (urinary excretion of deoxypyridinoline and N-terminal telopeptide) were also measured. RESULTS: The median values of faPWV and baPWV in RA patients were 1124 cm/s [interquartile range (IQR) 1040-1175] and 1539 cm/s (IQR 1297-1738), respectively, which were significantly greater than the respective values of 982 cm/s (IQR 819-1054; p < 0.001) and 1322 cm/s (IQR 1112-1398; p = 0.004) in controls. In multiple regression analysis, the presence of RA emerged as an independent factor associated with the greater faPWV and baPWV when adjusted for age, blood pressure, and smoking. In RA patients alone, BMD in the trabecular bone component, but not for the total bone (cortical plus trabecular), at the ultradistal radius correlated significantly with both faPWV and baPWV. Multiple regression analysis showed that trabecular BMD at the distal radius was a significant factor independently associated with greater faPWV and baPWV when adjusted for age, blood pressure, and smoking. None of the measured inflammation markers or bone resorption markers correlated with either faPWV or baPWV in patients with RA. CONCLUSION: Patients with RA show increased arterial stiffening, in addition to the arterial thickening we have previously reported, supporting the notion of enhanced atherosclerosis in RA patients. Paraarticular bone loss in the trabecular bone component at the ultradistal radius is a factor significantly associated with increased arterial stiffening in RA patients.

Amino Acids↗
PubMed2005

Expression of FGF23 is correlated with serum phosphate level in isolated fibrous dysplasia.

Fibrous dysplasia (FD) patients sometimes suffer from concomitant hypophosphatemic rickets/osteomalacia, resulting from renal phosphate wasting. It was recently reported that FD tissue in the patients with McCune-Albright syndrome (MAS) expressed fibroblast growth factor-23 (FGF-23), which is now known to be as a pathogenic phosphaturic factor in patients with oncogenic osteomalacia and X-linked hypophosphatemic rickets. Since it remains controversial whether serum phosphate levels are influenced by FGF23 expressions in FD tissue, isolated FD patients without MAS syndrome were examined for the relationship between FGF23 expressions, circulating levels of FGF-23 and phosphate to negate the effects of MAS-associated endocrine abnormalities on serum phosphate. Eighteen paraffin embedded FD tissues and 2 frozen tissues were obtained for the study. Sixteen of 18 isolated FD tissues were successfully analyzed GNAS gene, which exhibited activated mutations observed in MAS. Eight of 16 FD tissues, which exhibited GNAS mutations, revealed positive staining for FGF-23. These evidence indicate that postzygotic activated mutations of GNAS is necessary for the FD tissue formation by mosaic distribution of mutated osteogenic cell lineage, but is not sufficient to elevate FGF23 expression causing generalized osteomalacia with severe renal phosphate wasting. The expression level of FGF23 in isolated FD tissue with hypophosphatemic osteomalacia determined by real-time PCR was abundant close to the levels in OOM tumors. Osteoblasts/osteocytes in woven bone were predominant source of circulating FGF-23 in FD tissues by immunohistochemistry. A negative correlation of the intensity of FGF-23 staining with serum inorganic phosphate levels indicated that the expression of FGF23 in focal FD tissues could be a prominent determinant of serum phosphate levels in isolated FD patient. These data provide novel insights into the regulatory mechanism of serum inorganic phosphate levels in isolated FD patients and extend the notion that FGF-23 originating from FD tissue may cause hypophosphatemia not only in isolated FD patients but also in the patients with MAS syndrome.

Adolescent↗
PubMed2005

Associations between physical activity, peripheral atherosclerosis and bone status in healthy Japanese women.

The aim of this cross-sectional study was to investigate whether physical activity and bone status may affect arterial thickening and stiffening in healthy Japanese women. Healthy women (n = 149; mean age, 54 years) were recruited from those who participated in a local health check program at the Osaka City University Hospital. Physical activity was assessed by physical functioning score of SF-36, and bone status by bone mineral density (BMD) in lumbar spine and calcaneus osteo-sono index (OSI). Arterial wall thickening assessed by intima-media thickness (IMT) in common carotid artery (CA) and femoral artery (FA), and arterial wall stiffening by peak wave velocity (PWV) in heart-carotid (hc) and heart-femoral (hf) as central segment and in heart-brachial (hb) and femoral-ankle (fa) as peripheral segment, respectively. By Spearman Rank correlation, lumbar spine BMD was correlated negatively with CA IMT (rho = -0.225, p < 0.05) and FA IMT (rho = -0.215, p < 0.05), and calcaneus OSI with FA IMT (rho = -0.330, p < 0.0001) but not CA IMT (rho = -0051, p = 0.5335). Both lumbar spine BMD and calcaneus OSI correlated negatively with PWV in all segments (all p < 0.05). Physical functioning score correlated weakly but significantly in a negative manner with all PWV segments (all p < 0.05) but not IMT. Multiple regression analyses revealed a significant association of calcaneus OSI (beta = -0.240, p = 0.0039) but not lumbar spine BMD (beta = -0.067, p = 0.4541) with FA IMT, although neither lumbar spine BMD nor calcaneus OSI was associated with CA IMT. Furthermore, physical functioning score was independently associated with hb and fa PWV but not hc and hf PWV, suggesting the preferential association with peripheral segment including lower extremities. Neither lumbar spine BMD nor calcaneus OSI was associated with any segment of PWV. In conclusion, it was suggested that calcaneus OSI might be associated with arterial wall thickening preferentially in femoral artery, and that physical activity may be associated with arterial wall stiffening in peripheral segment including lower extremity but not in central segment in healthy Japanese women.

Atherosclerosis↗
PubMed2005

Proposed mechanism for diterpene synthases in the formation of phomactatriene and taxadiene.

To obtain insight into how the cyclization pathway is controlled, the mechanism of diterpene synthase reactions (the putative phomactatriene synthase and taxadiene synthases) involving the same intermediate was investigated in detail. The mechanism of the initial transformation of GGDP to verticillen-12-yl cation (A+) was proposed based on the labelling pattern of phomactatriene (9a) obtained in the feeding experiments with 13C-labelled acetates. To obtain information on the reaction pathway of A+ to 9a and taxadiene, reactions of verticillol with various acids were conducted. Structural determination of products allowed us to propose a reaction pathway via cations A+, D+, E+, F+ and G+. Identification of hydrocarbons in mycelial extracts of phomactin-producing fungus supported the proposed reaction mechanism. Based on the results of ab initio calculations for highly flexible cation intermediates, a mechanism is proposed.

Alkenes↗
PubMed2005

Hypercalcemia in a patient with primary hyperparathyroidism and acromegaly: distinct roles of growth hormone and parathyroid hormone in the development of hypercalcemia.

We herein report a case of primary hyperparathyroidism associated with acromegaly. Although serum parathyroid hormone (PTH) levels increased after the resection of a pituitary adenoma, levels of serum 1a, 25-dihydroxyvitamin D [1, 25(OH)2D] decreased but remained above the normal upper limit. After resection of a parathyroid adenoma, serum PTH, 1, 25(OH)2D, calcium (Ca), and phosphate were all normalized. Since serum 1, 25(OH)2D levels decreased in spite of the increase in serum PTH levels after normalization of levels of growth hormone (GH), GH may have contributed to the elevation of serum 1, 25(OH)2D. It is therefore suggested that the mechanism by which elevation of serum 1, 25(OH)2D occurred in the present case may involve an increase in serum GH distinct from the PTH-mediated pathway.

Acromegaly↗
PubMed2005

[Ibandronate as a new therapeutic agent for osteoporosis].

Ibandronate, a second generation amino-bisphosphonate has a high potency as much as the third generation bisphosphonates. Therefore this compound can be characteristically administrated by means of bolus intravenous injection. Moreover it is the first bisphosphonate prospectively shown antifracture efficacy for the intermittent administration in a randomized, controlled clinical trial.

Administration, Oral↗
PubMed2004

Significance of intima-media thickness in femoral artery in the determination of calcaneus osteo-sono index but not of lumbar spine bone mass in healthy Japanese people.

The aim of this cross-sectional study was to investigate whether physical activity and local arterial thickening may affect bone metabolism. To analyze the effects of physical activity and atherosclerosis on bone in healthy Japanese people, health-related quality of life (HRQL) and local arterial thickening were assessed by means of the Medical( )Outcomes Study 36-item Short Form (SF-36), and intimal-medial thickness (IMT) in common carotid artery (CA) and femoral artery (FA), respectively. Bone mineral density (BMD) in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. Healthy subjects (106 male and 154 female) were recruited from those who participated in a local health check program at the Osaka City University Hospital. A significant correlation existed between lumbar spine BMD and calcaneus OSI (r=0.551, P<0.0001). Among various scores in SF-36, only physical functioning score correlated weakly but significantly in a positive manner with lumbar spine BMD (rho=0.156, P=0.0147) and calcaneus OSI (rho=0.190, P=0.0024). Lumbar spine BMD correlated negatively with FA IMT (rho=-0.191, P=0.0027) whereas calcaneus OSI with FA IMT (rho=-0.199, P=0.0014). Multiple regression analyses revealed a significant association between FA IMT and calcaneus OSI, whereas lumbar spine BMD did not correlate significantly with FA or CA IMT. When subjects were restricted to female, FA IMT, but not CA IMT, still showed tendency against independent factors negatively associated with calcaneus OSI. Furthermore, lumbar spine BMD, but not calcaneus OSI, was weakly but significantly associated with increased physical functioning score independently. In conclusion, it was suggested that physical activity may affect bone strength in lumbar spine and calcaneus and that FA IMT might be a significant determinant of bone strength in calcaneus, but not in lumbar spine, in healthy Japanese subjects.

Arteriosclerosis↗
PubMed2003

Preferential reductions of paraarticular trabecular bone component in ultradistal radius and of calcaneus ultrasonography in early-stage rheumatoid arthritis.

Rheumatoid arthritis (RA) is a major cause of secondary osteoporosis and is frequently associated with both paraarticular and generalized osteoporosis. The present study was designed to investigate the preferential sites of reduction of bone mineral density (BMD), in the early stage of RA, with special emphasis on the differential effect of RA on BMD in trabecular and cortical components. The participants (30 RA patients and 26 healthy participants) were all female with disease duration of less than 1 year. BMD in the radius was measured at 4% (ultradistal site) and 20% (midshaft) to the ulnar length proximal to the end of radius by peripheral quantitative computed tomography. BMD in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. RA patients showed lower BMD preferentially in the trabecular component, but not in cortical bone component of the ultradistal radius than age-matched normal controls. Calcaneus OSI was also significantly reduced. The radial midshaft and lumbar spine did not differ significantly between RA patients and normal controls. Trabecular BMD in the ultradistal radius exhibited negative correlations with serum CRP, ESR, and RF, and calcaneus OSI with M-HAQ score. In conclusion, it was suggested that disease activity of RA and impairment of daily physical activity might be a significant determinant of deterioration of bone structure in paraartciular distal radius and calcaneus, respectively, in early-stage RA patients.

Activities of Daily Living↗
PubMed2003

Synthesis, resolution, and absolute stereochemistry of (-)-blestriarene C.

A naturally occurring 1,1'-biphenanthrene, blestriarene C (1), was prepared in 13 steps and 30% overall yield. The key steps are the ester-mediated nucleophilic aromatic substitution on 2,6-di-tert-butyl-4-methoxyphenyl 5-isopropoxy-2-methoxybenzoate (4) by 2-methoxy-4-methoxymethoxy-6-methylphenylmagnesium bromide (5) and a novel intramolecular cyclization of the resulting 4-isopropoxy-2'-methoxy-4'-methoxymethoxy-6'-methylbiphenyl-2-carboxylic ester 14 to 7-isopropoxy-4-methoxy-2-(methoxymethoxy)phenanthren-9-ol (15). The racemic blestriarene C was optically resolved by chiral HPLC on a preparative scale to give several 10-mg yields of both the enantiomers in up to 95% ee. The absolute stereochemistry was determined to be S(a)-(-) by the axial chirality recognition method, which was based on the stereospecific formation of a 12-membered cyclic diester containing two biaryl-o,o'-diyl unites joined by ester -CO(2)- linkages. The validity of the method was confirmed by an X-ray crystallographic analysis and ab initio conformational analyses of such 12-membered cyclic diesters. It was found that blestriarene C and its 7,7'-diisopropyl ether 2 underwent rapid photoracemization even under ambient light exposure.

Chromatography, High Pressure Liquid↗
PubMed2003

Inflammation and bone resorption as independent factors of accelerated arterial wall thickening in patients with rheumatoid arthritis.

OBJECTIVE: We recently reported that rheumatoid arthritis (RA) patients had increased intima-media thickness (IMT) of the common carotid artery (CCA). The present longitudinal study was performed to determine whether the change in arterial thickness was accelerated in RA patients and to determine which factor was important in the progression of arterial wall changes. METHODS: We studied 62 female RA patients with stable disease activity and 63 healthy female controls. IMT of the CCA was measured twice by high-resolution B-mode ultrasonography. The second examination was performed 18-36 months after the first, and changes were expressed as millimeters of increase per year. Baseline examinations included blood markers of inflammation and urinary calcium excretion (expressed as the calcium-to-creatinine ratio). RESULTS: RA patients showed a significantly greater increase in IMT of the CCA compared with controls. In univariate analyses of the RA patient data, the C-reactive protein (CRP) level correlated with the increase in CCA IMT. Other markers of inflammation (the erythrocyte sedimentation rate and white blood cell and platelet counts) also showed significant positive associations with the annual increase in CCA IMT in multiple regression models when adjusted for age, smoking status, blood pressure, and serum cholesterol level. The urinary calcium-to-creatinine ratio was also significantly associated with an increase in CCA IMT. Moreover, both the CRP level and the urinary calcium-to-creatinine ratio were significantly and independently associated with the increase in IMT of the CCA. CONCLUSION: Patients with RA have a higher rate of increase in thickening of the arterial wall. Inflammation and calcium mobilization are factors closely associated with the accelerated arterial wall changes.

Arteriosclerosis↗
PubMed2003

Successful treatment of multicentric reticulohistiocytosis with alendronate: evidence for a direct effect of bisphosphonate on histiocytes.

We describe the case of a 44-year-old Japanese woman with severe nodular erythematous skin lesions and arthritis mutilans who was admitted for further treatment of multicentric reticulohistiocytosis. Skin and synovial biopsies showed heavy infiltration with tartrate-resistant acid phosphatase-positive histiocytes and multinucleated giant cells. Immunohistochemical analysis showed that some of the mononuclear cells in the skin were positive for RANKL. After 1 month of Alendronate, an aminobisphosphonate, given at a dosage of 10 mg once a week intravenously for the first 6 weeks and then once a month thereafter, the arthritis and skin nodules improved, and the remission has continued for more than 2 years. The findings in this patient suggest that osteoclast-like multinucleated giant cells differentiate locally in the skin from infiltrating histiocytes with the help of RANKL-positive stromal cells and that alendronate acts directly on cells of monocyte/macrophage lineage in humans. Thus, alendronate should be added to the list of drugs for the treatment of multicentric reticulohistiocytosis.

Adult↗
PubMed2003

Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays.

The number of known mRNA transcripts in the mouse has been greatly expanded by the RIKEN Mouse Gene Encyclopedia project. Validation of their reproducible expression in a tissue is an important contribution to the study of functional genomics. In this report, we determine the expression profile of 57,931 clones on 20 mouse tissues using cDNA microarrays. Of these 57,931 clones, 22,928 clones correspond to the FANTOM2 clone set. The set represents 20,234 transcriptional units (TUs) out of 33,409 TUs in the FANTOM2 set. We identified 7206 separate clones that satisfied stringent criteria for tissue-specific expression. Gene Ontology terms were assigned for these 7206 clones, and the proportion of 'molecular function' ontology for each tissue-specific clone was examined. These data will provide insights into the function of each tissue. Tissue-specific gene expression profiles obtained using our cDNA microarrays were also compared with the data extracted from the GNF Expression Atlas based on Affymetrix microarrays. One major outcome of the RIKEN transcriptome analysis is the identification of numerous nonprotein-coding mRNAs. The expression profile was also used to obtain evidence of expression for putative noncoding RNAs. In addition, 1926 clones (70%) of 2768 clones that were categorized as "unknown EST," and 1969 (58%) clones of 3388 clones that were categorized as "unclassifiable" were also shown to be reproducibly expressed.

Animals↗
PubMed2003

[Clinical application of bisphosphonates, present and future].

For the present, bisphosphonates are widely applicable;secondary osteoporosis, metastatic bone diseases, primary hyperparathyroidism, osteogenesis imparfecta, inflammatory bone and joint disorders besides primary osteoporosis, hypercalcemia of malignancy, Paget's disease of bone, and so on. More expansion of its clinical application in the future is greatly expected with elucidation of the mechanism of action.

English Abstract↗
PubMed2002

Identification of genes regulating colorectal carcinogenesis by using the algorithm for diagnosing malignant state method.

We studied the expression profiles of various stages of colorectal tumors (adenoma (AD), seven samples; carcinoma (CA), 16 samples) by using cDNA microarrays and developed ADMS (algorithm for diagnosing malignant state) method, selecting 335 clones characteristic of CA state. We, then, applied ADMS to 12 additional samples (five from primary lesions with metastasis and seven metastases); all 16 CAs and 12 metastatic tumors were diagnosed correctly as cancerous states. Although three of the seven ADs were diagnosed as "cancerous," the large size of two of these tumors suggested their potential malignancy. Our strategy for selecting clones characteristic of the malignant state is widely applicable to diagnosis and for predicting the stage of progression during multistep carcinogenesis. Of the 335 clones we selected, 135 were known genes. Included in the 135 genes were tumor suppressor and growth factor-related genes and were consistent with the literature. ADMS is a reliable means for identifying genes useful for the diagnosis of cancer.

Adenoma↗