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Biomedical subjects

T Tamaki

Publications and source records attributed to T Tamaki.

At least 19 recordsLinked to original sources

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↗

Effect of pitavastatin on apolipoprotein A-I production in HepG2 cell.

There are few reports describing the mechanism of HDL-elevating action of HMG-CoA reductase inhibitors (statins). As it is considered that the key step of HDL production is the secretion of apolipoprotein A-I (apoA-I), we investigated the effect of statins on apoA-I synthesis and secretion by HepG2 cell to elucidate the mechanism of the action. Each statin induced apoA-I expression (mRNA and protein) dose-dependently: the rank order of the apoA-I induction pitavastatin (3 microM)>simvastatin (10 microM)>atorvastatin (30 microM). The induction of apoA-I by statins disappeared with addition of mevalonate, which indicates that the effect is HMG-CoA reductase inhibition-dependent. Based on HMG-CoA reductase inhibition, pitavastatin-induced apoA-I more efficiently than simvastatin and atorvastatin. Further study revealed that pitavastatin increased ABCA1 mRNA in HMG-CoA reductase-dependent manner and that Rho and Rho kinase inhibitor (C3T and Y27632) increased apoA-I production in the HepG2 cells. These results suggest that pitavastatin efficiently increases apoA-I in the culture medium of HepG2 cells by promoting apoA-I production through inhibition of HMG-CoA reductase and suppression of Rho activity and by protecting apoA-I from catabolism through ABCA1 induction and lipidation of apoA-I.

Apolipoprotein A-I↗

Use of diffusion-weighted magnetic resonance imaging in empyema after cranioplasty.

External decompression can be an effective treatment for acute intracranial hypertension, but the cranial defect must be repaired. The most serious complication of cranioplasty is late infection. Confusing an empyema that occurs after cranioplasty with a fluid collection (haematoma or liquor) can have catastrophic consequences, such as the development of cerebritis. The goal of this study was to assess the ability of diffusion-weighted (DW) magnetic resonance imaging (MRI) to diagnose empyema after cranioplasty. DW MRI and apparent diffusion coefficient (ADC) maps were studied in six patients with surgically verified empyema after cranioplasty. The findings were compared with those in five patients who had surgically verified haematoma or liquorrhoea. In the patients with empyema, the lesion was hyperintense, whereas the fluid collections (haematoma and liquorrhoea) were visualized as hypointense lesions. The ADC maps showed that empyema had a significantly lower intensity than the fluid collections (haematoma or liquorrhoea). DW MRI can be used to identify empyema after cranioplasty and can help to differentiate it from other fluid collections. Hence, this is a useful additional imaging modality for the diagnosis of empyema after cranioplasty.

Adolescent↗

Cardiopulmonary haemodynamic changes after severe head injury.

Haemodynamic studies were performed by pulmonary artery catheter in 15 patients with severe head injury. To our knowledge, few data are available about the detailed haemodynamic changes after head injury using pulmonary artery catheter. All patients were assessed by the Glasgow Coma Scale, computed tomography and intracranial pressure monitoring. We divided the patients into hypotensive and normotensive groups. All patients showed a high pulmonary vascular resistance and a high pulmonary capillary wedge pressure, probably due to pulmonary vasoconstriction. In the hypotensive group, the two major changes were a marked decrease of the cardiac index and a slight increase of systemic vascular resistance. The low cardiac index was the result of heart failure secondary to myocardial dysfunction. In contrast, the normotensive group was characterized by a high systemic vascular resistance that was induced by generalized vasoconstriction. Increased intracranial pressure is initially associated with an increase of the cardiac index and systemic vascular resistance, so patients with severe head injury also suffer from profound circulatory disturbance.

Adult↗

Treatment of supracondylar fracture of the humerus in children by skeletal traction in a brace.

In 1980, we developed a specially designed brace for treating supracondylar fractures of the humerus in children, along with an easy and safe technique of reduction by skeletal traction. This method, which takes into consideration only the medial tilting and anterior angulation of the distal fragment, achieves complete reduction, ignoring any lateral, posterior and minor rotational displacements of the fragment. Skeletal traction is applied through a screw inserted into the olecranon and the angulation at the fracture site is reduced regardless of the anatomical position without manipulation. We treated 193 children with displaced supracondylar fractures of the humerus using this method between 1980 and 2001. Only four children (2%) developed cubitus varus. The majority obtained an excellent range of movement at the elbow; one had a 25 degree limitation of flexion. This technique is an effective and easy method of treating supracondylar fractures of the humerus in children.

Braces↗

Development of cone and plate-type rheometer for quantitative analysis of endothelial cell detachment by shear stress.

We developed an apparatus, which has a structure based on a cone and plate-type rheometer, to facilitate quantitative analysis of the detachment process of endothelial cells (EC) from diverse materials including 3-dimensional scaffolds such as plate, membrane and porous-shaped materials. As an artificial vascular model, a material inoculated with EC to a polycarbonate membrane coated with laminin was prepared. In consequence, reduced cell number, medium volume, and material size was enough to evaluate cell detachment from various materials by shear stress in our system. When shear stress was loaded to a material with EC, the ratio retained of initially inoculated cells decreased with time. Increase of magnitude of shear stress also decreased the ratio. We conclude that our apparatus could analyze quantitatively detachment of EC with ease for screenings to find materials that enhance adhesive force of EC. To produce artificial blood vessels with small diameter, our apparatus could become a useful instrument.

Cell Adhesion↗

Endothelin-1 is a potent stimulator of alpha1beta1 integrin-mediated collagen matrix remodeling by rat mesangial cells.

Endothelin-1 (ET) is known to stimulate mesangial cell (MC) proliferation, extracellular matrix (ECM) synthesis, and thereby contribute to the progression of glomerulonephritis (GN). To clarify the molecular and cellular mechanisms of how ET is involved in the development of glomerular sclerosis, we investigated the influence of ET on the MC-alpha1beta1 integrin-mediated collagen matrix reorganization using a collagen gel contraction assay. ET enhanced MC-alpha1beta1 integrin-mediated gel contraction in a dose-dependent manner. Addition of the endothelin A (ETA) receptor antagonist, BQ123, into collagen gels abolished ET-induced gel contraction by MC. Cell behavior involved in ET-induced gel contraction was investigated in combination with function-blocking anti-alpha1-integrin antibody. Migration and adhesion assays revealed that ET stimulated alpha1beta1 integrin-mediated MC migration but did not influence cell adhesion to type I collagen (collagen I). Integrin-function blocking studies using anti-alpha1 integrin antibody indicated that MC-alpha1beta1 integrin is required not only for collagen-dependent migration, but also for gel contraction. Zymography showed that ET increased MC matrix metalloproteinase-2 (MMP-2) activity in a dose-dependent manner during MC-induced gel contraction process. Finally, flow cytometry analysis indicated that ET did not affect the cell surface expression of the MC-alpha1beta1 integrin within the collagen gel. These data suggested that ET promotes collagen matrix reorganization through the enhancement of MC-alpha1beta1 integrin-dependent migration and MMP-2 activity. We therefore conclude that ET is a potential molecule inducing pathological collagen matrix remodeling observed in progressive GN.

Animals↗

Anti-U5 snRNP antibody as a possible serological marker for scleroderma-polymyositis overlap.

OBJECTIVE: To determine the prevalence of the anti-U5 small nuclear ribonucleoprotein (snRNP) antibody in patients with systemic sclerosis. METHODS: Sera from 281 patients with systemic sclerosis, including 10 patients with overlapping polymyositis, were assayed using RNA immunoprecipitation and protein immunoprecipitation. RESULTS: Only one serum sample showed precipitation of U5 snRNA with scarce precipitation of U2, U1, U4 and U6 snRNAs. In addition, the serum precipitated a 200 kDa protein. The serum was from a 35-yr-old Japanese male patient with overlapping systemic sclerosis and polymyositis accompanied by large-cell lung carcinoma. The clinical appearance was similar to that of a case reported previously. CONCLUSION: The presence of the anti-U5 snRNP antibody in serum may be specific for scleroderma-polymyositis overlap syndrome.

Adult↗

Kienböck's disease in systemic lupus erythematosus.

We report two cases of Kienböck's disease associated with systemic lupus erythematosus SLE. The characteristics of these cases associated with SLE differed from those previously reported for Kienböck's disease. Corticosteroid may be a cause of Kienböck's disease in SLE.

Adult↗

Reconstruction of a scalp and skull defect with free latissimus dorsi myocutaneous flap following dermatofibrosarcoma protuberans.

A 53-year-old male underwent more than 10 surgical treatments over 14 years, including a simple excision and local flap transfer, after recurrences of dermatofibrosarcoma protuberans of the head. Clinical results indicated that simple excision of dermatofibrosarcoma protuberans should not be performed as initial treatment. Instead, free flap transplantation, which permits a wide excision and complete reconstruction, should be the first treatment option.

Dermatofibrosarcoma↗

Rotatory subluxation of the scaphoid in Kienböck's disease is not a cause of scapholunate advanced collapse (SLAC) in the wrist.

We have examined whether the rotatory subluxation of the scaphoid which is seen in patients with advanced Kienböck's disease is associated with scapholunate advanced collapse (SLAC) wrist. We studied 16 patients (11 men, 5 women) who had stage-IV Kienböck's disease with chronic subluxation of the scaphoid. All had received conservative treatment. The mean period of affection with Kienböck's disease was 30 years (14 to 49). No wrist had SLAC. In eight patients, 24 years or more after the onset of the disease, the articular surface of the radius had been remodelled by the subluxed scaphoid with maintenance of the joint space. The wrists of six patients were considered to be excellent, nine good, and one fair according to the clinical criteria of Dornan. Our findings have shown that rotatory subluxation of the scaphoid in Kienböck's disease is not a cause of SLAC wrist and therefore that scaphotrapeziotrapezoid arthrodesis is not required for the management of these patients.

Adolescent↗

Lumbar canal stenosis caused by hypertrophy of the posterior longitudinal ligament: case report.

STUDY DESIGN: This is a case report of a patient with hypertrophy of the posterior longitudinal ligament (HPLL) in the lumbar spine, with assessment of operative treatment and a 10-year follow-up using magnetic resonance imaging. OBJECTIVES: To report on the long-term outcome of a case of lumbar HPLL, to review the literature on case reports of HPLL, and to outline the pathology of HPLL in the lumbar spine. SUMMARY OF BACKGROUND DATA: There have been several reports of HPLL in the cervical spine and thoracic spine. However, the authors found no reports of this condition in the lumbar spine and no reports of long-term follow-up. Two types of pathology are associated with HPLL: primary hypertrophy of the ligament and secondary hypertrophy associated with intervertebral disc herniation. METHODS: A 10-year follow-up evaluation of a 56-year-old man with HPLL at L2 is reported. The patient was observed using serial physical examinations, radiographs, and MRIs over 10 years. Because he did not respond to conservative management, surgical treatment was applied. After complete decompression by hemilaminectomy and resection of hypertrophied ligament, the nerve roots were freed of constriction through the neural foramens at L2 and L3. RESULTS: One year after the operation the patient was asymptomatic without evidence of recurrence of the disease. CONCLUSIONS: HPLL is a very rare disease. This appears to be the first report of the disease in the lumbar spine.

Humans↗

Effects of losartan in combination with or without exercise on insulin resistance in Otsuka Long-Evans Tokushima Fatty rats.

Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. To gain further information on this effect, we examined the effect of losartan on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Losartan administration alone lowered systolic blood pressure, but did not improve oral glucose tolerance test or insulin resistance in OLETF rats. However, the administration of losartan with exercise significantly improved both systolic blood pressure and insulin resistance relative to control OLETF rats. On the other hand, losartan treatment, regardless of exercise, increased glucose uptake in excised soleus muscle and fat cells. To explore the beneficial effect of losartan on skeletal muscle glucose uptake, we examined intracellular signaling of soleus muscle. Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation.

Adipocytes↗

Using cineradiography for continuous dynamic-motion analysis of the lumbar spine.

STUDY DESIGN: Cineradiography was used to analyze continuous dynamic motion in the lumbar spine. OBJECTIVES: To identify motion patterns of the lumbar spine in asymptomatic volunteers and symptomatic patients with L4 degenerative spondylolisthesis, and to use the findings to discuss segmental instability in this disorder. SUMMARY OF BACKGROUND DATA: The use of radiographic findings to assess lumbar spine instability remains controversial. Although some studies have reported on lumbar kinematics during actual movement, the motion patterns in asymptomatic volunteers and symptomatic patients with L4 degenerative spondylolisthesis have not been fully clarified. METHODS: While asymptomatic volunteers (n=20; mean age, 27; control group) and symptomatic patients with L4 degenerative spondylolisthesis (n=41; mean age, 63; degenerative spondylolisthesis [DS] group) flexed from a sitting neutral position and back to the neutral position (flexion course), cineradiography was used to record lateral segmental lumbar motions. Twelve frames were selected during the flexion course, and flexion-extension angle (f-e angle) and translation in the sagittal plane were measured at each motion segment (L2-L3, L3-L4, L4-L5, and L5-S1). The DS group was classified into 2 subgroups according to percentage of slip: DS group I, with a slip equal to or less than 15%; and DS group II, with a slip of more than 15%. The motion pattern was compared between the groups. RESULTS: In the control group, f-e angle and translation at the L2-L3, L3-L4, and L4-L5 segments moved simultaneously, although the L5-S1 segment showed an initial delay. The amount of f-e angle and translation changed almost symmetrically. In both f-e angle and translation, the L4-L5 segment showed a large motion pattern. In DS group I (n=21), the L4-L5 segment showed a large motion pattern in f-e angle and an intermediate motion pattern in translation. In DS group II (n=20), the L4-L5 segment showed an intermediate motion pattern in f-e angle, and a small motion pattern in translation. The relative range of f-e angle at the L4-L5 segment had the largest range in DS group I, and the relative translation showed a serial decrease from the control group through DS group II. A significant correlation between f-e angle and translation (harmonious motion pattern) was noted at the L2-L3, L3-L4, and L4-L5 segments in the control group. The harmonious motion pattern at the L4-L5 segment was significantly less in the DS group than in the control group. The loss of harmonious motion pattern (disordered motion pattern) at L4-L5 was well-revealed in the DS group II. CONCLUSIONS: Motion analyses using cineradiography helped to explain the phenomena of lumbar spine kinematics. Based on continuous dynamic-motion analysis with cineradiography, large f-e angle and disordered motion pattern during the flexion-backward course in the DS group I was considered to be caused by segmental instability. The decreased translation and disordered motion pattern throughout the flexion course in the DS group II was considered to be caused by restabilization.

Adult↗

Requirement for tyrosine kinase-ERK1/2 signaling in alpha 1 beta 1 integrin-mediated collagen matrix remodeling by rat mesangial cells.

Abnormal mesangial extracellular matrix remodeling by mesangial cells (MCs) is the hallmark of progressive glomerulonephritis (GN). We recently showed, using a type I collagen gel contraction assay, that alpha 1 beta 1 integrin-dependent MC adhesion and migration are necessary cell behaviors for collagen matrix remodeling. To further determine the mechanism of alpha 1 beta 1 integrin-mediated collagen remodeling, we studied the signaling pathways of MCs that participate in the regulation of collagen gel contraction. Immunoprecipitation and phosphotyrosine detection revealed that gel contraction is associated with the enhanced activity and phosphorylation of ERK1/2 by MCs. The tyrosine kinase inhibitors herbimycin and genistein inhibited collagen gel contraction dose dependently. Furthermore, targeting ERK1/2 activity with a MEK inhibitor, PD98059, and antisense ERK1/2 hindered gel contraction in a dose-dependent manner. Similar inhibitory effects on gel contraction and ERK1/2 phosphorylation were observed when MC-mediated gel contraction was performed in the presence of function-blocking anti-alpha1 or anti-beta1 integrin antibodies. However, cell adhesion and migration assays indicated that PD98059 and antisense ERK1/2 blocked alpha 1 beta 1 integrin-dependent MC migration, but did not interfere with collagen adhesion, although there was a marked decrease in ERK1/2 phosphorylation and ERK1/2 protein expression in cell adhesion on type I collagen. None of the above could affect membrane expression of alpha 1 beta 1 integrin. These results suggested that ERK1/2 activation is critical for the alpha 1 beta 1 integrin-dependent MC migration necessary for collagen matrix reorganization. We therefore conclude that ERK1/2 may serve as a possible target for pharmacological inhibition of pathological collagen matrix formation in GN.

Animals↗

Prognostic significance of BRCA1 expression in Japanese sporadic breast carcinomas.

BACKGROUND: BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian carcinoma syndrome. The primary objective of the current study was to investigate the influence of BRCA1 expression on the prognoses of sporadic breast carcinomas. METHODS: A cohort of 175 Japanese women with invasive breast carcinoma who had no family history in first-degree relatives was studied. Expression of BRCA1 was determined by an immunohistochemical procedure in which the MS110 monoclonal antibody was used. Kaplan--Meier and Cox proportional regression survival analyses were used to compare negative and positive BRCA1 patients. RESULTS: One hundred fifteen (65.7%) of the 175 specimens showed positive BRCA1 staining (> 10% cells were immunoreactive). During a median follow-up of 4.4 years, negative BRCA1 patients had worse disease free survival than positive BRCA1 patients (35 % vs. 7%, respectively; P < 0.0001). BRCA1 expression was significantly inversely correlated with histologic grade (P < 0.0001) but not with lymph node status or other conventional prognostic markers. In multivariate analysis using the Cox regression model, positive BRCA1 emerged as an independent prognostic indicator for disease free survival. CONCLUSIONS: The results of this study suggest that BRCA1 may be a valuable marker for identifying women with sporadic breast carcinoma at high risk of developing recurrence, and who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.

Adult↗

Evaluation of carriers of bone morphogenetic protein for spinal fusion.

STUDY DESIGN: Posterolateral lumbar transverse process fusion in a rabbit model was performed using two different carriers for recombinant human morphogenetic protein-2, one having a porous structure and the other being a Type I collagen sheet. OBJECTIVES: To compare the effectiveness of two different carriers for recombinant human morphogenetic protein-2 in achieving lumbar intertransverse process arthrodesis. SUMMARY OF BACKGROUND DATA: The application of osteoinductive growth factors at various anatomic sites, such as in long bones and spinal segments, has been performed experimentally by many researchers. Although many carriers of osteoinductive factors have been reported, the most effective carrier has not been established. We have reported the efficacy of sintered bovine bone, True Bone Ceramics, which is coated with Type I collagen as a carrier of recombinant human bone morphogenetic protein-2 in achieving lumbar intertransverse process arthrodesis. True Bone Ceramics is a crystallized form of bone minerals made from sintering bovine bone at high temperatures and possesses natural trabecular structure. The crystalline character of True Bone Ceramics is similar to that of artificial hydroxyapatite. In this study we focused on the structure of two different carriers to facilitate osteosynthesis in lumbar arthrodesis. METHODS: Fifty-four adult rabbits underwent bilateral lumbar intertransverse process arthrodesis at L4-L5. The animals were divided into five groups and had implants placed as follows: Group 1, autograft group, harvested autologous corticocancellous bone from the posterior iliac crest; Group 2, TBC group, True Bone Ceramics alone; Group 3, TBC-TBMP group, True Bone Ceramics coated with Type I collagen infiltrated with 100 microg of recombinant human bone morphogenetic protein-2; Group 4, collagen group, Type I collagen sheet; and Group 5, collagen-BMP group, implanted collagen sheet containing 100 microg of recombinant human bone morphogenetic protein-2. Spinal fusion was evaluated by radiographic analysis, manual palpation, biomechanical testing, and histologic examination at both 3 and 6 weeks after surgery. RESULTS: Radiographs in the TBC-TBMP group showed a continuous trabecular pattern within the intertransverse area at 3 weeks after surgery. The fusion mass in the intertransverse area was more prominent than in the other groups. At 3 weeks after surgery the TBC-TBMP group had higher fusion rates based on manual palpation, and the fusions showed significantly higher tensile strength and stiffness. The histologic findings in the TBC-TBMP group at 3 weeks after surgery showed a cortical bone rim around the edge of the fusion mass, and contiguous new bone appearing between the recipient bone and the matrix of TBC without evidence of foreign body formation. In the collagen-BMP group, less mature bone formation was present within the grafted area and the new bone was not contiguous, even at 6 weeks after surgery. CONCLUSIONS: As a carrier for recombinant human bone morphogenetic protein-2, True Bone Ceramics, possessing a bony or porous structure, was more effective than a Type I collagen sheet in achieving a faster and stronger lumbar spinal fusion in a rabbit model.

Animals↗

Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs.

An effective method for determination of the levels of newly discovered 31-amino acid endothelins [ETs(1-31)] as well as big ETs and 21-amino acid ETs [ETs(1-21)], in human lungs has been developed. About 85% of ETs in human lung homogenates were recovered on acid extraction 8 times. Most of the published protocols for the determination of tissue ETs involve a reverse-phase minicolumn to separate proteins from peptides, after which the levels of ETs are directly determined by enzyme immunoassay. The levels determined, however, include fairly high amounts of non-bioactive ET metabolites in tissues and the data reported are diverse. We established an effective methods for the extraction and the separation of nine different muscle constricting ETs from their metabolites on a reverse-phase C18 column. Using this protocol, the levels of ETs in human lungs were determined by means of a sandwich-enzyme immunoassay specific for each ET derivative. The levels of ET-2(1-21) were the highest among those of ETs, and the levels of ETs(1-31) were in a similar range to those of big ETs but were lower than those of ETs(1-21). This method can be utilized to assess the pathophysiological roles of ETs(1-31) in various human organs.

Chromatography, High Pressure Liquid↗