Search PubMed⌕ Search

Biomedical subjects

Y Iwamoto

Publications and source records attributed to Y Iwamoto.

At least 91 records · Page 5Linked to original sources
PubMed2001

H-ras oncogene mutation in dedifferentiated liposarcoma. Polymerase chain reaction-restriction fragment length polymorphism analysis.

Point mutations of the ras gene family (K-ras, H-ras, and N-ras) are thought to be involved in the development of a variety of human tumors. Dedifferentiated liposarcoma is characterized by the coexistence of well-differentiated (WD) and high-grade anaplastic (HG) components. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 34 liposarcomas, comprising 15 well-differentiated liposarcomas and 19 dedifferentiated liposarcomas, and in 8 storiform-pleomorphic type malignant fibrous histiocytomas (MFHs) using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. The 2 components of dedifferentiated liposarcoma were analyzed independently. H-ras mutations were seen only in dedifferentiated liposarcomas (4/19 [21%]), 1 in WD components and 3 in HG components. The mutation was not seen in any of 15 cases of well-differentiated liposarcoma. MFHs showed an H-ras mutation in 1 (12%) of 8 cases. Our results seem to suggest that the H-ras mutation is a relatively uncommon event in dedifferentiated liposarcoma, which may demonstrate an epiphenomenon of dedifferentiation in dedifferentiated liposarcoma.

Adult↗
PubMed2001

Mechanical strain effect on bone-resorbing activity and messenger RNA expressions of marker enzymes in isolated osteoclast culture.

Adaptive modeling and remodeling are controlled by the activities of osteoblasts and osteoclasts, which are capable of sensing their mechanical environments and regulating deposition or resorption of bone matrix. The effects of mechanical stimuli on isolated osteoclasts have been scarcely examined because it has proven to be difficult to prepare a number of pure osteoclasts and to cultivate them on mineralized substratum during mechanical stimulation. Recently, we developed an apparatus for applying mechanical stretching to the ivory slice/plastic plate component on which cells could be cultured. The loading frequency, strain rate, and generated strain over an ivory surface could be controlled by a personal computer. Using this apparatus, we examined the role of mechanical stretching on the bone-resorbing activity of the osteoclasts. Mature and highly enriched osteoclasts were cultured for 2, 12, and 24 h on the ivory/plate component while being subjected to intermittent tensile strain. The stretched osteoclasts showed enhanced messenger RNA (mRNA) expression levels of osteoclast marker enzymes, tartrate-resistant acid phosphatase (TRAP), and cathepsin K and increases of resorbed-pit formation, suggesting that the mechanical stretching up-regulated the bone-resorbing activity of the osteoclasts. A stretch-activated cation (SA-cat) channel blocker significantly inhibited the increases of the mRNA level and pit formation after 24 h of stretching. This study suggested the possibility that the mature osteoclasts responded to mechanical stretching through a mechanism involving a SA-cat channel in the absence of mesenchymal cells and, as a result, up-regulated their bone-resorbing activity.

Acid Phosphatase↗
PubMed2001

ATP-Sensitive potassium channels modulate glucose transport in cultured human skeletal muscle cells.

Several lines of evidence suggest that ATP-sensitive potassium (KATP) channels are involved in glucose uptake by insulin target tissues. The aim of the present study was to prove directly the effect of KATP channel activity on glucose transport into cultured human skeletal muscle cells. We used potassium channel openers PCO-400 and nicorandil alone or in combination with channel blockers glibenclamide and gliclazide to examine their effects on insulin- or high glucose concentration-induced glucose uptake using 2-deoxy-D-3H-glucose or 3-O-methyl-D-3H-glucose as tracer, respectively. PCO-400 inhibited the basal (non-stimulated) uptake of 2-DG or 3-OMG at the glucose concentration of 5 mM. PCO-400 and nicorandil dose-dependently inhibited insulin-stimulated glucose uptake, and their inhibitory effects were reversed by glibenclamide or gliclazide. In addition, PCO-400 inhibited high glucose concentration-facilitated glucose transport in the absence of insulin, and this effect was also antagonized by both sulfonylurea drugs. Regarding the mechanism by which KATP channels modulate glucose transport, we focused on protein kinase C (PKC), because PKC has been supposed to participate in both insulin- and high glucose concentration-stimulated glucose transport. PMA (phorbol 12-myristate 13-acetate) dose-dependently reversed the PCO-400-induced suppression of insulin-stimulated glucose uptake. On the other hand, PCO-400 at the concentration that inhibited glucose uptake caused no alteration of membrane-associated PKC activity in the presence of insulin or PMA. From these results we conclude that KATP channels modulate the basal and insulin-or high glucose level-stimulated glucose transport in skeletal muscle through a mechanism independent of PKC.

3-O-Methylglucose↗
PubMed2001

The effect of antimicrobial periodontal treatment on circulating tumor necrosis factor-alpha and glycated hemoglobin level in patients with type 2 diabetes.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) may play an important role in insulin resistance. In this study, we hypothesized that TNF-alpha produced due to periodontal inflammation synergistically affects insulin resistance as well as TNF-alpha produced from adipose tissues in insulin-resistant type 2 diabetes patients. Therefore, to understand the effects of antimicrobial periodontal therapy on serum TNF-alpha concentration and subsequent metabolic control of diabetes, we examined the periodontal and diabetic status on 13 type-2 diabetes patients. METHODS: These patients were treated with local minocycline administration in every periodontal pocket around all existing teeth once a week for a month. Before and after treatment, the number of total bacteria in the periodontal pockets and circulating TNF-alpha concentration were measured and the HbA1c value was assessed. RESULTS: Antimicrobial therapy significantly reduced the number of microorganisms in periodontal pockets (P <0.01). After treatment, the circulating TNF-alpha level was significantly reduced (P <0.015). The HbA1c value was also reduced significantly (P <0.007). In addition, the 6 patients who were not receiving insulin therapy demonstrated decreased fasting insulin levels (P <0.03), and HOMA-R (P <0.03) indices. The average reductions in circulating TNF-alpha concentration and HbA1c value were 0.49 pg/ml and 0.8%, respectively. CONCLUSION: The results indicate that anti-infectious treatment is effective in improving metabolic control in diabetics, possibly through reduced serum TNF-alpha and improved insulin resistance.

Adult↗
PubMed2001

Mutations in the coding region of the neurogenin 3 gene (NEUROG3) are not a common cause of maturity-onset diabetes of the young in Japanese subjects.

Mutations in transcription factors that play a role in the development of the endocrine pancreas, such as insulin promoter factor-1 and NeuroD1/BETA2, have been associated with diabetes. Cell type-specific members of the basic helix-loop-helix (bHLH) family of transcription factors play essential roles in the development and maintenance of many differentiated cell types, including pancreatic beta-cells. Neurogenin 3 is a bHLH transcription factor that is expressed in the developing central nervous system and the embryonic pancreas. Mice lacking this transcription factor fail to develop any islet endocrine cells and die postnatally from diabetes. Because neurogenin 3 is required for the development of beta-cells and other pancreatic islet cell types, we considered it a candidate diabetes gene. We screened the coding region of the human neurogenin 3 gene (NEUROG3) for mutations in a group of unrelated Japanese subjects with maturity-onset diabetes of the young (MODY). We found three sequence variants: a deletion of 2-bp in the 5'-untranslated region (NEUROG3-g.-44-45delCA), a G-to-A substitution in codon 167 (g.499G/ A), resulting in a Gly-to-Arg replacement (G/R167), and a T-to-C substitution in codon 199 (g.596T/C), resulting in a Phe/Ser polymorphism F/S199. These polymorphisms were not associated with MODY, thereby suggesting that mutations in NEUROG3 are not a common cause of MODY in Japanese patients.

Amino Acid Substitution↗
PubMed2001

The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes.

The allele frequencies for a Pro12-->Ala substitution in peroxisome proliferator-activated receptor-gamma differ among ethnic groups, and its relationship with diabetes and associated diseases is controversial. The prevalence of this polymorphism and its effects on clinical characteristics have now been evaluated with a large number of Japanese individuals with type 2 diabetes (n = 2,201) and normal control subjects (n = 1,212) recruited by 10 institutions located in seven different cities in Japan. The allele frequency for the Ala12 variant was significantly lower in the type 2 diabetic group than in the control group (2.39 vs. 4.13%, P = 0.000054). However, compared with subjects without the Ala12 variant, the diabetic subjects with this variant exhibited a significantly higher serum concentration of total cholesterol (P = 0.001), manifested a reduced capacity for insulin secretion as evaluated by homeostasis model assessment (P = 0.007), and tended to possess a higher level of HbA1c. These data suggest that the Ala12 variant is associated with a reduced risk for the development of diabetes in the general population, but that it may be also a risk factor for insulin deficiency and disease severity in individuals with type 2 diabetes.

Adult↗
PubMed2001

Multiple pathways of angiotensin I conversion and their functional role in the canine penile corpus cavernosum.

Multiple pathways of angiotensin (Ang) I conversion and their functional role in the canine penile corpus cavernosum were investigated. Biochemical analysis revealed high activities of angiotensin-converting enzyme (ACE) (6.9 +/- 1.7 mU/mg of protein, mean +/- S.E.M., n = 8) and chymase-like enzyme (4.0 +/- 1.4 mU/mg of protein). Functional recording of isometric tension showed that Ang I (3 x 10(-7) M) induced a tension of 0.17 +/- 0.05 g (n = 5), which was reduced to about 60% by pretreatment with an ACE inhibitor, lisinopril (10(-6) M), and almost completely blocked by lisinopril in combination with a chymase inhibitor, chymostatin (10(-4) M). Binding sites for ACE and Ang II receptors were studied by in vitro autoradiography using 125I-351A and 125I-[Sar1, Ile8]Ang II as ligands, respectively. Dense binding of ACE appeared in the endothelial layer of the corpus cavernosum penis, and Ang II receptors were localized in the trabecular smooth muscle layer. An AT1 receptor antagonist, CV-11974 (10(-6) M), markedly displaced 125I-[Sar1, Ile8]Ang II bindings, indicating that the corpus cavernosum penis contains AT1 receptors exclusively. Immunohistochemical studies demonstrated ACE in the endothelium of the corpus cavernosum penis. Mast cells that produce chymase were present mainly in the cavernosal area. These results demonstrate that chymase, in addition to ACE, is involved in the contraction of canine penile corpus cavernosum through local Ang II formation.

Angiotensin I↗
PubMed2001

[Von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis: a case report].

We present a case report of von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis. A 26-year-old man appeared with painless tumors of the bilateral scrotal contents. Ultrasonography and other radiographic examinations including computed tomographic scan and dripinfusion pyelography showed multiocular tumors in the bilateral epididymis and a right renal tumor 3 cm in diameter. The tumors of the bilateral epididymis were surgically resected and of the right renal tumor enucleated. Histopathological examination revealed cystadenoma of the epididymis and renal cell carcinoma (clear cell carcinoma, G1, pT1a). He has not received adjuvant therapy, and is doing well with no evidence of metastatic disease 2 years after surgery.

Adult↗
PubMed2001

Effect of femoral and tibial component position on patellar tracking following total knee arthroplasty: 10-year follow-up of Miller-Galante I knees.

Rotational alignment of the femoral and tibial components using computed tomography (CT) was evaluated to establish if errors of alignment have a significant effect on patellofemoral complications. From 1987-1990, 54 knees in 39 patients were replaced with the Miller-Galante I knee system. Of these, 10 patients (13 knees) comprised this study. All patients had osteoarthritis. Mean patient age at surgery was 70.3 years. Mean follow-up was 10.3 years. On CT, rotational position of the femoral component relative to the epicondylar axis and the position of the tibial component relative to the tibial tubercle were evaluated. Patellar displacement and patellar tilt angle also were evaluated when the knee was flexed at 30 degrees. Mean rotation of the femoral component was 6.1 degrees of internal rotation (2.7 degrees-11.2 degrees). Mean rotation of the tibial component was 16.7 degrees of internal rotation (2.4 degrees-27.7 degrees). Mean lateral patellar tilt angle was 2.9 degrees (-6.0 degrees-11.9 degrees), and mean lateral displacement was 2.7 mm (-3.2-8.9 mm). Rotational position of both the femoral and tibial components showed a statistically significant correlation with the patellar tilt angle. This study showed the internally rotated femoral and tibial component were related to the patellar maltracking. This malalignment of the components, as well as nonanatomical patellar groove and metal-backed patellar component, could be one of the causes of the patellofemoral complications with the Miller-Galante I knee.

Aged↗
PubMed2001

A new concept for precise patella resection in total knee arthroplasty.

We developed a new patella-cutting guide that simplifies proper alignment and enables resection of the correct thickness of bone. This guide consists of a central shaft, two support frames, and a ring. The ring consists of upper and lower disks, with a slot between the disks. The central shaft and the lower disk have holes for fixation pins. The distance from the distal end of the central shaft to the lowest level of the slot is 8 mm. Bone of the same thickness as that of the patellar component can be automatically resected using this guide. A feeler gauge is inserted through the slot, and the periarticular region is felt. This procedure enables the guide to be set at the correct angulation. A laboratory study using fresh-frozen cadaver patella specimens and a clinical study showed that proper alignment and proper resection were achieved using this guide.

Arthroplasty, Replacement, Knee↗
PubMed2001

Subgingival microflora and antibody responses against periodontal bacteria of young Japanese patients with type 1 diabetes mellitus.

Periodontal disease is a complication of patients with type 1 diabetes mellitus (T1DM), although the mechanisms responsible for this relationship remain unclear. The aim of this study was to examine oral manifestations and the prevalence of periodontal pathogens from subgingival plaque samples and serum IgG antibody levels against them in young Japanese type 1 diabetic subjects. One hundred and seventeen Japanese T1DM subjects (53 male, 64 female, mean age +/- SD, 16 +/- 6.5 years) participated in this study. Thirty-nine periodontally healthy, age-matched nondiabetics served as controls. T1DM subjects were clinically assigned into three groups: 12 periodontitis, 32 gingivitis and 73 periodontally healthy. Microbiological tests for four periodontal pathogens, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia and Capnocytophaga ochracea were performed using 16S ribosomal RNA-based polymerase chain reaction methods. Serum IgG antibody levels against 12 periodontal bacteria including the four species assessed by polymerase chain reaction were measured by enzyme-linked immunosorbent assay. In the T1DM subjects, the Periodontitis group had a significantly longer mean duration of diabetes and a higher percentages of subjects harbouring P. gingivalis and P. intermedia than the Periodontally Healthy group. Serum IgG antibody levels against P. gingivalis were significantly elevated in the Periodontitis group compared with Gingivitis and Periodontally Healthy groups. These results indicate that Japanese T1DM subjects are a high-risk group for periodontal disease and both P. gingivalis infection and duration of T1DM are risk factors for the progression of periodontitis in patients with T1DM.

Adolescent↗
PubMed2000

Interaction with p53 enhances binding of cisplatin-modified DNA by high mobility group 1 protein.

A nonhistone chromosomal protein, high mobility group (HMG) 1, is ubiquitous in higher eukaryotic cells and binds preferentially to cisplatin-modified DNA. HMG1 also functions as a coactivator of p53, a tumor suppressor protein. We investigated physical interactions between HMG1 and p53 and the influence of p53 on the ability of HMG1 to recognize damaged DNA. Using immunochemical coprecipitation, we observed binding of HMG1 and p53. Interaction between HMG1 and p53 required the HMG A box of HMG1 and amino acids 363-376 of p53. Cisplatin-modified DNA binding by HMG1 was significantly enhanced by p53. An HMG1-specific antibody that recognized the A box of this protein also stimulated cisplatin-modified DNA binding. These data suggest that an interaction with either p53 or antibody may induce conformational change in the HMG1 A box that optimizes DNA binding by HMG1. Interaction of p53 with HMG1 after DNA damage may promote activation of specific HMG1 binding to damaged DNA in vivo and provide a molecular link between DNA damage and p53-mediated DNA repair.

Cell Nucleus↗
PubMed2000

Altered gene expression upon BCR cross-linking in Burkitt's lymphoma B cell line.

Burkitt's lymphoma cell line, BL2 was stimulated by surface BCR cross-linking and altered gene expression was analyzed by RDA methodology. Consistent with previous reports, we detected up-regulated MDC, IL6R and adhesion molecule LFA1. We also detected gene expression of SIRPalpha, anti-apoptotic A-20, signal regulatory SLP76 and BCAR3, DNA binding proteins EGR2 and DEC1 in addition to some new genes.

Antibodies↗
PubMed2000

The activity of soluble VCAM-1 in angiogenesis stimulated by IL-4 and IL-13.

IL-13 is a multifunctional lymphokine sharing a number of biological properties with IL-4. We previously observed that IL-4 shows angiogenic activities in vitro as well as in vivo. In this study we examined the effect of IL-13 on angiogenesis in vitro and in vivo and also the underlying mechanisms. Human IL-13 significantly stimulated the formation of tube-like structures in collagen gels by human microvascular endothelial cells and bovine aortic endothelial cells by about 3-fold over the controls in the absence of the cytokines. Administration of murine IL-13 led to neovascularization when implanted in the rat cornea. Coadministration of neutralizing mAb to the IL-4R inhibited both tubular morphogenesis in vitro and activation of STAT6 induced by IL-4 or IL-13. Both IL-4 and IL-13 markedly increased mRNA levels of VCAM-1 in vascular endothelial cells, and the production of the soluble form of VCAM-1 was also stimulated in response to IL-4 or IL-13. Administration of anti-VCAM-1 Ab in vitro blocked tubular morphogenesis induced by IL-4 and IL-13. Angiogenesis induced in vivo in rat cornea by IL-4 and IL-13 was also inhibited by Ab against the rat alpha4 integrin subunit. These findings suggest that angiogenesis dependent on IL-4 and IL-13 is mainly mediated through a soluble VCAM-1/alpha4 integrin pathway.

Animals↗
PubMed2000

The C-ring problem of sterol biosynthesis: TiCl(4)-induced rearrangement into the anti-Markovnikov cation corresponding to the C-ring.

[reaction: see text] Cation 9, generated by the reaction of diol 8 and BF(3).Et(2)O, SnCl(4), Sc(OTf)(3), FeCl(3), TiF(4), or CF(3)SO(3)H, leads to a hydride shift, providing cation 11, which corresponds to the initiation of backbone rearrangement. On the other hand, TiCl(4) selectively induces rearrangement to secondary cation 13 by ring expansion, which corresponds to the C-ring formation of sterol biosynthesis. AlCl(3) and ZrCl(4) induce further rearrangement into six-membered ring tert-cation 16.

Cations↗
PubMed2000

Evidence for brainstem structures participating in oculomotor integration.

The cerebellar flocculus has been implicated in vestibulo-oculomotor control. One major central input to this structure originates from brainstem cells in the paramedian tract (PMT), whose function is unknown. Here it is reported that PMT cells in the pons carry vestibular and eye movement signals and their pharmacological inactivation produces a leaky integrator combined with vestibular imbalance. The results suggest that PMT cells provide the cerebellum with sensory and motor signals that are essential for velocity-to-position integration, a common premotor process that is required in all motor systems.

Action Potentials↗
PubMed2000

Ectopic p16(ink4) expression enhances CPT-11-induced apoptosis through increased delay in S-phase progression in human non-small-cell-lung-cancer cells.

A tumor-suppressor gene, p16(INK4), which is deleted or mutated in tumors, regulates cell-cycle progression through a G(1)-S restriction point by inhibiting CDK4(CDK6)/cyclin-D-mediated phosphorylation of pRb. We have found that ectopic p16(INK4) expression increased cellular sensitivity of human non-small-cell-lung-cancer (NSCLC) A549 cells to a selective growth-inhibitory effect induced by the topoisomerase-I inhibitor 11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11) in vitro. In this study, we observed enhanced apoptosis characterized by DNA fragmentation in A549 cells transfected with p16(INK4) cDNA (A549/p16-1) and treated with CPT-11. This apoptosis was suppressed by the inhibitor of interleukin-1beta-converting enzyme (ICE/caspase-1) or ICE-like proteases, Z-Asp-CH2-DCB, as determined by DNA fragmentation and proteolytic cleavage of poly(ADP-ribose) polymerase, a natural substrate for CPP32/caspase-3. In A549/p16-1 cells, cytosolic peptidase activities that cleaved Z-DEVD-7-amino-4-trifluoromethylcoumarin increased during CPT-11-induced apoptosis and were suppressed by a highly specific caspase-3 and caspase-3-like inhibitor, Z-DEVD-fluoromethylketone. These findings indicate that p16(INK) is positively involved in the activation pathway of the caspase-3 induced by CPT-11. The increased delay in S-phase progression and subsequent induction of apoptosis were observed in CPT-11-treated A549/p16-1 cells on the basis of DNA histograms. Specific down-regulation of the cyclin-A protein level in A549/p16-1 cells was observed after CPT-11-treatment, whereas cyclin B, cdk2, and cdc2 protein levels were unaffected. These results suggest that ectopic p16(INK4) expression inappropriately decreases cyclin A and thereby terminates CPT-11-induced G(2)/M accumulation, which is followed by increased apoptosis in p16(INK4)-expressing A549 cells.

Antineoplastic Agents, Phytogenic↗