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Biomedical subjects

T Tanizawa

Publications and source records attributed to T Tanizawa.

At least 19 recordsLinked to original sources

Disappearance of hyperplastic polyps in the stomach after eradication of Helicobacter pylori. A randomized, clinical trial.

BACKGROUND: Helicobacter pylori infection is common in patients with hyperplastic gastric polyps. OBJECTIVE: To study the effect of eradication of H. pylori on the clinical course of patients with hyperplastic gastric polyps. DESIGN: Single-blind, randomized, controlled trial. SETTING: University-based gastroenterology outpatient clinic. PATIENTS: 35 patients with H. pylori infection and hyperplastic gastric polyps at least 3 mm in diameter. INTERVENTION: Patients were randomly assigned to a treatment group (n = 17), which received a proton-pump inhibitor (omeprazole or lansoprazole), amoxicillin, and either clarithromycin or ecabet sodium, or to a control group (n = 18), which received no treatment. MEASUREMENTS: Patients underwent endoscopy before enrollment and 12 to 15 months after the end of treatment. Serum gastrin levels and titers of IgG to H. pylori were measured. RESULTS: In the treatment group, the polyps had disappeared by 3 to 15 months (average, 7.1 +/- 1.2 months) after the end of treatment in 12 of all 17 patients (71%) and in 12 of the 15 patients (80%) in whom H. pylori was eradicated. However, 12 to 15 months after the start of the study, no change in polyps or H. pylori status was seen in any controls (P < 0.001). Histologic findings of inflammation and activity, serum gastrin levels, and titers of IgG to H. pylori showed significant regression in the treatment group compared with the control group (P < 0.01). CONCLUSIONS: Most hyperplastic polyps disappeared after eradication of H. pylori. Thus, eradication should be attempted before endoscopic removal is done in patients with hyperplastic gastric polyps and H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles

Localization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia.

Frequent apoptosis in the bone marrow of patients with myelodysplastic syndromes (MDS) was demonstrated on frozen sections using the terminal deoxytransferase (TdT)-mediated dUTP nick end labeling (TUNEL) method. The overall mean percentage of TUNEL-positive cells was about 17% in the bone marrow of MDS, while bone marrow from control cases exhibited a mean of 3.4% (P < 0.001). To elucidate the mechanism of apoptosis in bone marrow cells of MDS, the expression of Fas antigen and Fas ligand (FasL) was examined by RT-PCR and immunohistochemistry. All MDS cases showed expression of Fas mRNA (12/12) and most exhibited an expression of FasL mRNA (10/12) by RT-PCR. Basically, control cases did not show positive signals for Fas and FasL mRNA, however, a very weak band was detected in three cases (3/10) for Fas and in one case (1/10) for FasL mRNA by RT-PCR. Immunohistochemical examination revealed positive staining for Fas (11/12) and FasL (12/12) in the bone marrow of MDS, while all the bone marrow samples from control cases were negative for anti-Fas (0/15) and for anti-FasL (0/15) antibody. Double staining clarified that TUNEL-positive apoptotic cells expressed Fas antigen on the cell surface, although not all Fas-positive cells were TUNEL positive. The Fas-positive cells of MDS bone marrow included hematopoietic cells expressing CD34 antigen, neutrophil elastase, a marker for myeloid series of cells, or glycophorin A, a marker for erythroid cells. However, CD68-positive cells which were macrophage lineage cells, did not express Fas antigen strongly. In contrast, positive staining for FasL was detected in hematopoietic cells and CD68-positive cells in the bone marrow of MDS. These results suggest that the Fas-FasL system plays an important role in inducing apoptosis in the bone marrow of MDS and works in an autocrine (hematopoietic cell-hematopoietic cell interaction) and/or paracrine (hematopoietic cell-stromal cell interaction) manner.

Adult

A morphometric comparison of trabecular structure of human ilium between microcomputed tomography and conventional histomorphometry.

Recently, an imaging technique using microcomputed tomography (micro-CT) has emerged as a method for nondestructively assessing the microarchitecture of unprocessed surgical bone biopsy specimens. Using micro-CT, two-dimensional (2D) axial images were obtained from undecalcified transiliac bone biopsies which were taken from 15 patients with various metabolic bone diseases. Total area, bone area, and bone perimeter were determined, from which the bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated semiautomatically and instantaneously. To evaluate the validity of this technique as a useful tool, the results were compared with those obtained from conventional histomorphometry. There were significant correlations between the two techniques for all parameters, with correlation coefficients ranging from 0.759 (Tb.N, P < 0.005) to 0.949 (BV/TV, P < 0.0001). Different resolutions seem to lead to major differences in perimeter values measured by the two methods. These factors may explain why the correlation coefficients of Tb.N and Tb.Th estimated from the perimeter and area is lower than that of BV/TV. Our results show that the micro-CT based on 2D images is a useful tool for imaging and nondestructively quantifying the microarchitecture of trabecular bone in unprocessed surgical bone specimens.

Adult

Effects of intermittent administration of low dose human PTH(1-34) on cancellous and cortical bone of lumbar vertebral bodies in adult beagles.

This study assessed the effect of low dose human parathyroid hormone [hPTH(1-34)] administration on cancellous and cortical bone of lumbar vertebrae in intact male beagles. 16 19-20-month-old beagle dogs were randomized into four groups: in group 1, the vehicle control group, saline was injected daily; in group 2, the sequential group, 0.375 microg/kg of PTH was injected daily for 4 weeks, then off 8 weeks, and this sequence was once repeated for another 4 and 8 weeks; in group 3, the same dose of PTH was injected once per week for 24 weeks; and, in group 4, PTH was injected three times per week for 24 weeks. Histomorphometric assessment on cancelllous and cortical bone (both ventral and dorsal shell) and two-dimensional node-strut analysis were done on the fifth lumbar vertebral bodies after calcein double bone labeling. In intact adult beagles, on the group treated with 0.375 microg/kg per day three times per week (group 4): (1) had a higher mean value in cancellous bone formation parameters [osteoid surface (+74%), osteoid volume (twofold), mineral apposition rate (+21%), and bone formation rate (twofold)]; (2) exhibited no effect on cortical thickness and porosity in both the ventral and dorsal shell; and (3) showed a lower mean value of node to termini (0.11 +/- 0.02 vs. 0.22 +/- 0.09) and a higher mean value of cortex to node (0.18 +/- 0.06 vs. 0.08 +/- 0.02), but not in trabeculae to trabeculae node, than age-related controls. In conclusion, we found that a low dose of PTH administration: (1) stimulated cancellous bone formation; (2) improved connectivity of trabeculae joined to the cortex; (3) did not decrease cortical thickness; and (4) did not increase cortical porosity in both ventral and dorsal cortexal shell of the lumbar vertebrae during this dosage and period in intact male beagles.

Animals

Overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma by bone marrow cells from patients with myelodysplastic syndromes.

To clarify whether regulatory cytokines inhibit hematopoiesis in patients with myelodysplastic syndromes (MDS), malignancies characterized by the formation of cytopenias despite the presence of cellular bone marrow, expression of TNF-alpha and IFN-gamma by bone marrow cells was investigated using specific reverse transcriptase-polymerase chain reaction assays. An enhanced expression of the mRNA for TNF-alpha was observed in most of the samples from MDS patients (11/14, 79%), whereas no enhancement was observed in bone marrow samples from AML (0/6), CML (0/2) or control cases (0/8). The expression of IFN-gamma was also enhanced in some of MDS cases (5/12, 42%) while AML (0/5), CML (0/2) and control cases (0/6) showed very low levels of IFN-gamma mRNA expression. Immunohistochemical examination confirmed the scattered presence of TNF-alpha or IFN-gamma producing cells in the bone marrow of MDS patients. The majority of these cells were CD68-positive macrophage lineage cells. These results suggested that disruption of hematopoiesis in MDS might be caused by enhanced production of inhibitory regulatory cytokines especially TNF-alpha and occasionally IFN-gamma by bone marrow macrophages.

Adult

Granulocyte-macrophage colony-stimulating factor abrogates transforming growth factor-beta 1-mediated cell cycle arrest by up-regulating cyclin D2/Cdk6.

The role of positive and negative cytokine interactions in G1 cell cycle regulation of haemopoietic cells was analysed by determination of the expression patterns of D-type cyclins and cyclin-dependent kinases (cdks) in SKM-1 myelodysplastic syndrome (MDS) cells incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or transforming growth factor-beta 1 (TGF-beta 1). TGF-beta 1 inhibited SKM-1 cell proliferation due to the cell cycle arrest in G1 phase. GM-CSF abrogated the TGF-beta 1-mediated G1 arrest in these cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TGF-beta 1-mediated G1 arrest correlated with the down-regulation of cdk4, cdk6 and cyclin D2, and that abrogation of TGF-beta 1-mediated G1 arrest by GM-CSF correlated with the constitutive over-expression of cyclin D2 and cdk6 but not cdk4. These results suggest the importance of cyclin D2/cdk6 levels in abrogating G1 arrest in cells exposed to TGF-beta 1, and raise the possibility that the GM-CSF-mediated up-regulatory pathway of signal transduction through cyclin D2/cdk6 differs from the TGF-beta 1-cdk4-mediated pathway in SKM-1 cells. This signal transduction pathway through cyclin D2/cdk6 might play an important role in haemopoietic regulation by the cytokine network.

Cell Cycle

Maintaining bone mass by bisphosphonate incadronate disodium (YM175) sequential treatment after discontinuation of intermittent human parathyroid hormone (1-34) administration in ovariectomized rats.

Intermittent treatment with human parathyroid hormone (1-34) [hPTH(1-34)] stimulates bone formation and increases cancellous bone mass in ovariectomized (OVX) rats. But PTH-induced cancellous bone rapidly disappears upon cessation of treatment. The fate of cortical bone treated by PTH has not been well characterized. Incadronate disodium (disodium cycloheptylaminomethylenedisphosphonate monohydrate, YM175) was expected to be antiresorptive without inhibiting bone formation. The purposes of this study were to determine (1) whether PTH treatment increases new cancellous and cortical bone mass and bone formation, (2) whether the new bone could be maintained by YM175 sequential treatment, and (3) whether the maintenance effect is persistent after YM175 withdrawal. Eighty-eight 11-week-old Sprague-Dawley rats were divided into sham operation and OVX groups. The OVX rats were treated for 8 weeks with the subcutaneous intermittent injection of 30 micrograms/kg of hPTH(1-34) three times a week beginning 4 weeks after surgery, then PTH treatment was withdrawn and YM175 (10 micrograms/kg) was injected subcutaneously three times a week for 4 weeks. YM175 treatment was withdrawn for the last 8 weeks of the protocol. The results of microstructural assessment in proximal tibial metaphysis and bone mineral density in distal and proximal femur demonstrated that PTH treatment for 8 weeks restored bone mass to the sham control level. However, after cessation of PTH treatment, the PTH-induced tibial cancellous bone mass showed a decrease at 4 weeks and almost totally disappeared after 12 weeks. Conversely, YM175 treatment maintained the PTH-induced tibial cancellous bone mass, and the bone continued to be maintained after 8 weeks of withdrawal of the YM175. Cortical bone was not lost during PTH treatment. YM175 maintained the PTH-induced new tibial cancellous bone in OVX rats by suppressing remodeling.

Animals

Changes in biological activity of bone cells in ovariectomized rats revealed by in situ hybridization.

Twelve-week-old female rats were ovariectomized (OVX) and compared with sham-operated control rats at 3, 5, 7, 10, 14, 30, and 60 days postoperation with respect to the expression of type I collagen and osteopontin mRNAs, as well as bone structure and the number of osteoclasts. The trabecular number and separation were significantly decreased and increased, respectively, in the metaphyseal trabecular bones of OVX rat femurs. The number of osteoclasts was significantly increased in the same region of OVX rats at 3 and 5 days postoperation. Type I collagen mRNA was expressed in osteoblasts, and osteopontin mRNA was expressed in some osteoclasts, in mononuclear cells on the bone resorption surface, and in osteocytes near the resorption surface. In the metaphyseal trabecular bone, type I collagen and osteopontin mRNA expression levels in individual cells was initially increased in OVX rats from 7 to 10 days postoperation, and this was sustained for 60 days. The number of osteopontin mRNA-expressing osteocytes was also significantly increased at 10 days postoperation, which lasted until 60 days. In the epiphysis, an increase in type I collagen mRNA expression was initially observed in OVX rats at 14 days postoperation, which lasted until 60 days. The number of osteopontin mRNA-expressing osteocytes was virtually identical until 30 days postoperation in the epiphysis. These findings indicated that the biological activities of osteoblasts and osteocytes are stimulated in bones of the OVX rat and that the response for OVX differs between the metaphysis and epiphysis. Furthermore, the number of osteopontin mRNA-expressing osteocytes was increased only in bones that tended to be resorbed after OVX. This indicates that some osteocytes were stimulated to express osteopontin mRNA by estrogen deficiency and suggests that these osteopontin mRNA-expressing osteocytes may be involved in regulation of bone metabolism.

Analysis of Variance

Effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on rat bone: inhibition of bone formation at the endosteal surface of vertebra and tibia.

The effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on bone was evaluated by histomorphometry using Sprague-Dawley rats. rh G-CSF was injected at doses of 0, 50, 150, and 450 microg/kg for 6 weeks. In vivo double fluorochrome labeling was performed before sacrifice. No significant change in body weight was observed. Bone mineral density (BMD) of lumbar vertebrae and femora was significantly decreased in G-CSF-treated groups. In the lumbar vertebra, osteoid surface, osteoid thickness, trabecular thickness, and labeled surface in G-CSF-treated groups were also significantly lower. In addition, osteoclast number and osteoclast surface were significantly higher in the G-CSF-treated groups. The endocortical surface at the mid-tibia showed lower labeled surface and mineral apposition rate in G-CSF-treated groups, without significant changes at the periosteal surface. Furthermore, numerous granulocytes fully occupied the bone marrow area. We conclude that proliferating granulocytes in the bone marrow may inhibit bone-forming cells from contacting the bone surface, resulting in reduction of bone formation; and increased osteoclastic bone resorption induced by G-CSF treatment contributed to the reduction of BMD.

Animals

Bone particles disturb new bone formation on the interface of the titanium implant after reaming of the marrow cavity.

Histomorphometric studies were conducted in rats to determine whether bone particles would disturb new bone formation on the interface of titanium implants inserted after reaming of the marrow cavity. In eighty 10-week-old female Wistar rats, smooth-surfaced titanium alloy implants were inserted bilaterally into the marrow cavity after reaming in the distal femur. There were three experimental groups: in the irrigated femora, sterile saline was flushed through the medullary canal; in the particle femora, autologous bone particles were inserted into the intramedullary cavity; and in the reamed femora, the implant was inserted without procedures after reaming. The rats were sacrificed at one, two, four or eight weeks postoperatively, and Villanueva bone staining was applied for histomorphometric studies. The bone volume of new bone on the interface of the implant in the irrigated femora was greater than that in the particle or the reamed femora throughout the study period. The results suggest that clearance of bone particles by irrigation after reaming of the marrow cavity significantly facilitates new bone formation on the interface of implants by one week. The findings also suggest the potential clinical application of total canal irrigation prior to insertion of cementless femoral components as well as cemented prosthesis.

Absorptiometry, Photon

Reactive lymphoid hyperplasia of the liver characterized by an angiofollicular pattern mimicking Castleman's disease.

A case of reactive lymphoid hyperplasia of the liver exhibiting a characteristic angiofollicular pattern is reported. A hepatic nodular lesion was discovered by abdominal echography during clinical follow-up of abnormal liver function tests. It was diagnosed as hepatocellular carcinoma because of its hypervascularity when observed by angiography, and surgically resected. Grossly, the lesion was well-demarcated and measured 2 cm in diameter. Microscopically, the nodule was composed of lymph follicles with germinal centers, and the hyalinized inter-follicular space contained abundant hyalinized vasculature and plasma cells. The surrounding liver tissue exhibited chronic inflammation with some peculiar angiofollicular structures mimicking Castleman's disease. An immunohistochemical study revealed that the angiofollicular structure had the same characteristics as a lymph follicle with a germinal center, and that the plasma cells proliferating in the inter-follicular space had polyclonal immunophenotypes. These histological and immunohistochemical findings indicated that the angiofollicular structure observed was a kind of reactive lymph follicle, and that this hepatic lesion was reactive lymphoid hyperplasia rather than Castleman's disease or an inflammatory pseudotumor.

Aged

Decrease of mesangial matrix after immunosuppressive therapy in children with reversible membranoproliferative glomerulonephritis type I.

We followed the course of membranoproliferative glomerulonephritis (MPGN) type I after immunosuppressive therapy in 10 children. At diagnosis all patients had abnormal urinary findings. After a mean follow-up of 14 years all but one patient showed normal urinalysis and renal function. Glomerular morphometry revealed an increase in the ratio of mesangial matrix area to glomerular area (M/G%) in all patients. After immunosuppressive treatment, a second biopsy was performed, which showed a significantly decreased M/G% in 4 patients. In 3 of the remaining 6, the mean M/G% was significantly lower in a third biopsy when compared with the first. In addition, there was a negative correlation between M/G% and duration from onset disease to biopsy (r = -0.46, p <0.05). Fifteen biopsies (6 initial and 9 repeat biopsies) were examined for the staining of various extracellular matrices. In the initial biopsy type IV collagen, type V collagen and fibronectin were increased in expanded mesangial areas. Type III collagen was found segmentally in a few biopsies only. M/G% correlated with the grade of type IV collagen, type V collagen and fibronectin staining. These findings suggest that a reversible clinical course of MPGN type I in children is paralleled by a decrease of mesangial matrix expansion.

Adolescent

[Successful induction of immune tolerance and novel hemostatic effects in a hemophilia A with high-responder inhibitor by regular infusions of factor VIII].

A hemophilia A patient with high responder inhibitor had been treated by (activated) prothrombin complex concentrates (A) PCC and activated factor VII until the occurrence of intracranial bleeding at the age of 6 years. Since the inhibitor titer was decreased less than 1 Bethesda Units/ml, high dose of factor VIII was given followed by the infusions of factor VIII concentrates (100 units/kg) three times a week. In spite of previous episodes of anamnestic responses by factor VIII products before, the inhibitor titer did not increase and disappeared completely 6 months after the FVIII infusion therapy. The specific anti-factor VIII IgG subclasses of the inhibitor were IgG2 and IgG4. The inhibitor recognized both light and heavy chains. He have no bleeding episode for 6 months since the beginning of the prophylactic with factor VIII concentrates.

Blood Coagulation Factors

A histomorphometric study on effects of single and concurrent intermittent administration of human PTH (1-34) and bisphosphonate cimadronate on tibial metaphysis in ovariectomized rats.

This study compared the single administration of hPTH(1-34), bisphosphonate cimadronate (YM-175), and concurrent therapy of these two for restoration of lost bone mass in ovariectomized (OVX) rats. Animals were untreated for 4 weeks after surgery, and then injected s.c. with vehicle (OVX+V), hPTH(1-34) (30 micrograms/kg) (OVX+P), YM-175 (5 micrograms/kg) (OVX+Y), or a combination of these two (OVX+P+Y), 3 days a week, for 8 weeks, and sacrificed. Their proximal tibia were processed undecalcified for quantitative bone histomorphometry. Although OVX+Y showed a reduction of bone turnover compared to OVX+V, it failed to restore lost bone mass in OVX rats. In contrast, OVX+P exhibited a stimulation of bone formation and restored cancellous osteopenia due to OVX. OVX+P+Y also resulted a recovery of osteopenia, however, stimulation of bone formation by PTH was suppressed by YM-175.

Animals

Discrepancy of response of hPTH administration and its withdrawal between trabecular and cortical bone sites in OVX rats.

We demonstrated the differences of response between trabecular and cortical bone sites in the rat induced by OVX and hPTH(1-34) administration [subcutaneous injection, 30 micrograms/kg, 3 times/week, for 12 weeks] and its withdrawal [for 8 weeks]. We observed that hPTH(1-34) administration in OVX rats partially prevented OVX-induced cancellous bone loss in the proximal tiabial metaphysis and added cortical bone in the tibial shaft. After cessation of hPTH treatment, bone loss was observed both in trabecular and cortical bone; however, it was more dramatic on endocortical surfaces.

Animals

[Bone histomorphometric analysis in primary hyperparathyroidism].

In primary hyperparathyroidism, bone remodeling is increased due to an enhanced activation frequency which is caused by excessive PTH. In mild cases, eroded, osteoid and labeled surfaces are increased. But as bone balance per remodeling cycle in cancellous bone is zero or even slightly positive, bone volume and structure are relatively maintained. In advanced cases, bone resorption is predominant in the endosteal surface of cortical bone, resulting in progressive thinning and increased porosity, cancellisation. As far cancellous bone resorption depth is deepened to occur trabecular perforation associated with fibrous tissue replacement, osteitis fibrosa.

Bone Remodeling