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S Takayama

Publications and source records attributed to S Takayama.

At least 37 records · Page 2Linked to original sources
PubMed2001

BAG-1: a novel biomarker predicting long-term survival in early-stage breast cancer.

PURPOSE: Among women with early-stage breast cancer treated with lumpectomy and radiation therapy, 30% to 40% will develop metastatic disease, which is often fatal. A need exists therefore for biomarkers that distinguish patients at high risk of relapse. We performed a retrospective correlative analysis of BAG-1 protein expression in breast tumors derived from a cohort of early-stage breast cancer patients. PATIENTS AND METHODS: Archival paraffin blocks from 122 women with stages I to II breast cancer treated with lumpectomy and radiation therapy (median follow-up, 12.1 years) were analyzed by immunohistochemical methods using monoclonal antibodies recognizing BAG-1 and other biomarkers, including Bcl-2, estrogen receptor, progesterone receptor, p53, and HER2/Neu. Immunostaining data were correlated with distant metastasis-free survival (DMFS) and overall survival (OS). RESULTS: Cytosolic immunostaining for BAG-1 was upregulated in 79 (65%) of 122 invasive breast cancers (P <.001) compared with normal breast. Elevated BAG-1 was significantly associated with longer DMFS and OS, overall (stages 1 and II) and in node-negative (stage I only) patients, on the basis of univariate and multivariate analyses (DMFS, P =.005; OS, P =.01, in multivariate analysis of all patients; DMFS, P =.005; OS, P =.001, in multivariate analysis of node-negative patients). All other biomarkers failed to reach statistical significance in multivariate analysis. Clinical stage was an independent predictor of OS (P =.04) and DMFS (P =.02). CONCLUSION: These findings provide preliminary evidence that BAG-1 represents a potential marker of improved survival in early-stage breast cancer patients, independent of the status of axillary lymph nodes.

Adult↗
PubMed2001

Structure-function analysis of Bag1 proteins. Effects on androgen receptor transcriptional activity.

Bag1 is a regulator of heat shock protein 70 kDa (Hsp70/Hsc70) family proteins that interacts with steroid hormone receptors. Four isoforms of Bag1 have been recognized: Bag1, Bag1S, Bag1M (RAP46/HAP46), and Bag1L. Although Bag1L, Bag1M, and Bag1 can bind the androgen receptor (AR) in vitro, only Bag1L enhanced AR transcriptional activity. Bag1L was determined to be a nuclear protein by immunofluorescence microscopy, whereas Bag1, Bag1S, and Bag1M were predominantly cytoplasmic. Forced nuclear targeting of Bag1M, but not Bag1 or Bag1S, resulted in potent AR coactivation, indicating that Bag1M possesses the necessary structural features provided it is expressed within the nucleus. The ability of Bag1L to enhance AR activity was reduced with the removal of an NH(2)-terminal domain of Bag1L, which was found to be required for efficient nuclear localization and/or retention. In contrast, deletion of a conserved ubiquitin-like domain from Bag1L did not interfere with its nuclear targeting or AR regulatory activity. Thus, both the unique NH(2)-terminal domain and the COOH-terminal Hsc70-binding domain of Bag1L are simultaneously required for its function as an AR regulator, whereas the conserved ubiquitin-like domain is expendable.

Animals↗
PubMed2001

Structural analysis of BAG1 cochaperone and its interactions with Hsc70 heat shock protein.

BAG-family proteins share a conserved protein interaction region, called the 'BAG domain', which binds and regulates Hsp70/Hsc70 molecular chaperones. This family of cochaperones functionally regulates signal transducing proteins and transcription factors important for cell stress responses, apoptosis, proliferation, cell migration and hormone action. Aberrant overexpression of the founding member of this family, BAG1, occurs in human cancers. In this study, a structure-based approach was used to identify interacting residues in a BAG1--Hsc70 complex. An Hsc70-binding fragment of BAG1 was shown by multidimensional NMR methods to consist of an antiparallel three-helix bundle. NMR chemical shift experiments marked surface residues on the second (alpha 2) and third (alpha 3) helices in the BAG domain that are involved in chaperone binding. Structural predictions were confirmed by site-directed mutagenesis of these residues, resulting in loss of binding of BAG1 to Hsc70 in vitro and in cells. Molecular docking of BAG1 to Hsc70 and mutagenesis of Hsc70 marked the molecular surface of the ATPase domain necessary for interaction with BAG1. The results provide a structural basis for understanding the mechanism by which BAG proteins link molecular chaperones and cell signaling pathways.

Adenosine Triphosphatases↗
PubMed2001

Molecular chaperone targeting and regulation by BAG family proteins.

Regulated changes in protein conformation can have profound effects on protein function, although routine laboratory methods often fail to detect them. The recently discovered BAG-family proteins may operate as bridging molecules that recruit molecular chaperones to target proteins, presumably modulating protein functions through alterations in their conformations, and ultimately affecting diverse cellular behaviours including cell division, migration, differentiation and death. Emerging knowledge about BAG-family proteins indicates that there may be a mechanism for influencing signal transduction through non-covalent post-translational modifications.

Amino Acid Sequence↗
PubMed2001

Origins and insertions of the triangular fibrocartilage complex: a histological study.

The origins and insertions of the triangular fibrocartilage complex (TFCC) were examined histologically in serially sectioned fresh-frozen cadaver wrists. The radioulnar ligament arose vertically through Sharpey's fibres from a broad area in the ulnar fovea and more horizontally from a narrow area at the base of the ulnar styloid. The floor of the extensor carpi ulnaris sheath also originated firmly from the dorsal side of the fovea of the ulna, through an arrangement of Sharpey's fibres. Loose ulnocarpally oriented fibres, corresponding to a thickened ulnar joint capsule, arose from the hyaline-like cartilage matrix at the tip of the ulnar styloid and inserted onto the triquetrum without Sharpey's fibres. The ulnolunate and ulnotriquetral ligaments originated not from the ulna, but from the palmar side of the TFCC. The insertion of the TFCC into the sigmoid notch of the radius demonstrated a central transition from the fibrocartilaginous disc into hyaline cartilage and a firmer fibroosseous transition of the dorsal and palmar portions of the radioulnar ligament at the periphery.

Adolescent↗
PubMed2001

Muscle repair after a transsection injury with development of a gap: an experimental study in rats.

Lacerated muscle needs fusion with muscle fibres to regain good function, but it often lose its elasticity and the repair seems poor. We think that the scar healing is caused by the development of a gap. In this study in 20 rats we made silicone tube models to keep a constant distance between the muscle ends, and examined the repair inside the silicone tube. In the short gap (1 mm), aligned collagen fibres and muscle fibres bridged both ends. However, when the gap was long (4 mm) they could not bridge both ends and collagen fibres covered the cut ends of muscle. Muscle contains a large fibrous component and will regenerate simultaneously after transsection injury. This result suggests that fibrous repair influences the muscle repair and muscle regeneration will be disturbed as the gap widens.

Animals↗
PubMed2001

Production of interleukin-8 and nitric oxide in human periapical lesions.

Bacterial infection of the pulp and root canal system leads to the recruitment of immunocompetent cells in the periapex and stimulates inflammatory cell responses to produce a variety of inflammatory mediators. Cytokines, reactive oxygen intermediates, and reactive nitrogen intermediates are frequently found at sites of acute inflammation. In this study, we measured the levels of interleukin (IL)-8 and nitric oxide (NO) in the periapical exudate (PE) from human periapical lesions and investigated the association of these mediators with the clinical symptoms of periapical periodontitis. PE samples were collected from root canals during routine endodontic treatments. The IL-8 concentration was measured by the enzyme-linked immunosorbent assay, and the NO level was measured as nitrite/nitrate concentration assayed by the Griess reaction. Detectable levels of IL-8 and nitrite/nitrate were found in 24 and 19 of 27 PE-samples, respectively. Although PE-IL-8 and nitrite/nitrate concentration showed a broad range, a significantly positive correlation was found between both mediators. Also, significantly higher IL-8 levels were found in PE from lesions that had painful symptoms at the sampling visit. However, there was no relationship between elevated NO levels and clinical symptoms. These results suggest that the up-regulation of IL-8 may have a critical role in the development of the symptoms of periapical disease.

Analysis of Variance↗
PubMed2001

A pollen coat protein, SP11/SCR, determines the pollen S-specificity in the self-incompatibility of Brassica species.

Many flowering plants have evolved self-incompatibility (SI) systems to prevent inbreeding. In the Brassicaceae, SI is genetically controlled by a single polymorphic locus, termed the S-locus. Pollen rejection occurs when stigma and pollen share the same S-haplotype. Recognition of S-haplotype specificity has recently been shown to involve at least two S-locus genes, S-receptor kinase (SRK) and S-locus protein 11 or S-locus Cys-rich (SP11/SCR). SRK encodes a polymorphic membrane-spanning protein kinase, which is the sole female determinant of the S-haplotype specificity. SP11/SCR encodes a highly polymorphic Cys-rich small basic protein specifically expressed in the anther tapetum and in pollen. In cauliflower (B. oleracea), the gain-of-function approach has demonstrated that an allele of SP11/SCR encodes the male determinant of S-specificity. Here we examined the function of two alleles of SP11/SCR of B. rapa by the same approach and further established that SP11/SCR is the sole male determinant of SI in the genus Brassica sp. Our results also suggested that the 522-bp 5'-upstream region of the S9-SP11 gene used to drive the transgene contained all the regulatory elements required for the unique sporophytic/gametophytic expression observed for the native SP11 gene. Promoter deletion analyses suggested that the highly conserved 192-bp upstream region was sufficient for driving this unique expression. Furthermore, immunohistochemical analyses revealed that the protein product of the SP11 transgene was present in the tapetum and pollen, and that in pollen of late developmental stages, the SP11 protein was mainly localized in the pollen coat, a finding consistent with its expected biological role.

Agrobacterium tumefaciens↗
PubMed2001

The protein non-folding problem: amino acid determinants of intrinsic order and disorder.

To investigate the determinants of protein order and disorder, three primary and one derivative database of intrinsically disordered proteins were compiled. The segments in each primary database were characterized by one of the following: X-ray crystallography, nuclear magnetic resonance (NMR), or circular dichroism (CD). The derivative database was based on homology. The three primary disordered databases have a combined total of 157 proteins or segments of length.30 with 18,010 residues, while the derivative database contains 572 proteins from 32 families with 52,688 putatively disordered residues. For the four disordered databases, the amino acid compositions were compared with those from a database of ordered structure. Relative to the ordered protein, the intrinsically disordered segments in all four databases were significantly depleted in W, C, F, I, Y, V, L and N, significantly enriched in A, R, G, Q, S, P, E and K, and inconsistently different in H, M, T, and D, suggesting that the first set be called order-promoting and the second set disorder-promoting. Also, 265 amino acid properties were ranked by their ability to discriminate order and disorder and then pruned to remove the most highly correlated pairs. The 10 highest-ranking properties after pruning consisted of 2 residue contact scales, 4 hydrophobicity scales, 3 scales associated with.-sheets and one polarity scale. Using these 10 properties for comparisons of the 3 primary databases suggests that disorder in all 3 databases is very similar, but with those characterized by NMR and CD being the most similar, those by CD and X-ray being next, and those by NMR and X-ray being the least similar.

Amino Acids↗
PubMed2001

Cubital tunnel release with lift-type endoscopic surgery.

A new technique of endoscopic release of the ulnar nerve at the elbow was designed for cubital tunnel syndrome. After three 5 mm incisions were made along the line of the ulnar nerve, the skin and subcutaneous tissue were lifted up using a fine tape to produce a provisional space. An endoscope was inserted through the one incision, and the constricting ligaments and fascia were released using a retrograde knife inserted through the other incision under endoscopic vision. Eight patients were treated using this method, and successful results were achieved. No neurovascular complications occurred, and all pre-operative complaints were resolved within three weeks. Our surgical series indicated an earlier return to work and daily activity due to early healing of incisions and minimal post-operative pain.

Adult↗
PubMed2001

Soft lithography in biology and biochemistry.

Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in basrelief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (> or = 50 microns), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.

Animals↗
PubMed2001

Hepatic parasympathetic (HISS) control of insulin sensitivity determined by feeding and fasting.

In response to insulin, a hormone [hepatic insulin sensitizing substance (HISS)] is released from the liver to stimulate glucose uptake in skeletal muscle but not liver or gut. The aim was to characterize dynamic control of HISS action in response to insulin and regulation of release by hepatic parasympathetic nerves. Insulin action was assessed by the rapid insulin sensitivity test, where the index is the glucose required (mg/kg) to maintain euglycemia after a bolus of insulin. Blocking HISS release by interruption of the hepatic parasympathetic nerves by surgical denervation, atropine, or blockade of hepatic nitric oxide synthase produced similar degrees of insulin resistance and revealed a similar dynamic pattern of hormone action that began 3--4 min after, and continued for 9--10 min beyond, insulin action (50 mU/kg). HISS action accounted for 56.5 +/- 3.5% of insulin action at insulin doses from 5 to 100 mU/kg (fed). We also tested the hypothesis that HISS release is controlled by the feed/fast status. Feeding resulted in maximal HISS action, which decreased progressively with the duration of fasting.

Anesthesia↗
PubMed2001

Periodontal regeneration by FGF-2 (bFGF) in primate models.

We recently demonstrated that a topical application of basic fibroblast growth factor (FGF-2; bFGF) to alveolar bone defects in beagle dogs enhanced periodontal regeneration. The purpose of this study was further characterization of the biological effects of FGF-2 in non-human primates. Thirty-two inflamed furcation class II defects were surgically created in 4 male primates. The gelatinous carrier alone or the carrier containing 0.1 or 0.4% human recombinant FGF-2 was topically applied to the defects and compared with no treatment. Eight weeks after application, the periodontal regeneration in those defects was analyzed. In all FGF-2-treated sites, significant periodontal regeneration was dose-dependently observed in greater amounts than in the carrier-treated or non-treated sites. No instances of epithelial down-growth, ankylosis, or root resorption were observed in the FGF-2-treated sites. These results indicate that a topical application of FGF-2 can enhance considerable periodontal regeneration in surgically created furcation class II defects of non-human primates.

Alveolar Bone Loss↗
PubMed2001

Tardy posterolateral rotatory instability of the elbow due to cubitus varus.

BACKGROUND: Cubitus varus has long been considered merely a cosmetic deformity. The purpose of this paper is to demonstrate a causal relationship between cubitus varus and instability of the elbow. METHODS: In twenty-four patients (twenty-five limbs) with a cubitus varus deformity following a pediatric distal humeral fracture or resulting from a congenital anomaly (three limbs of two patients), tardy posterolateral rotatory instability of the elbow developed approximately two to three decades after the deformity occurred. All patients presented with lateral elbow pain and recurrent instability. The average varus deformity was 15 degrees (range, 0 degrees to 35 degrees ). Surgery was performed in twenty-one patients (twenty-two limbs). Treatment consisted of reconstruction of the lateral collateral ligament and osteotomy in seven limbs, ligament reconstruction alone in ten, osteotomy alone in four, and total elbow arthroplasty in one. RESULTS: In three patients, the triceps muscle was dynamically stimulated intraoperatively to contract while resisting extension of the elbow. This produced posterolateral rotatory subluxation of the elbow, which was reversed by corrective osteotomy and lateral transposition of a portion of the medial head of the triceps that originally had been attached to the elongated, deformed medial aspect of the olecranon. At an average of three years (minimum, one year) after the operation, the result was good or excellent for nineteen of the twenty-two limbs that had undergone an operation; three limbs had persistent instability. CONCLUSIONS: With cubitus varus, the mechanical axis, the olecranon, and the triceps line of pull are all displaced medially. The repetitive external rotation torque on the ulna permitted by these deformities can stretch the lateral collateral ligament complex and lead to posterolateral rotatory instability. Thus, cubitus varus deformity secondary to supracondylar malunion or congenital deformity of the distal part of the humerus may not always be a benign condition and may have important long-term clinical implications. Operative correction can relieve symptoms of instability. The indications for preventive corrective osteotomy remain to be determined.

Adolescent↗
PubMed2001

[Clinicopathological study with regard to ulcer in the cancer lesion of the depressed type intramucosal cancer of the stomach].

UNLABELLED: We histologically investigated 207 cases with the depressed type intramucosal cancer of the stomach, as to the risk factor of ulcer formation in the cancer (Ul.), tumor size of less than and not less than 10 mm, histological type of differentiated carcinoma (Diff.) and undifferentiated carcinoma (Undiff.), tumor location classified by the usually occurring region of the peptic ulcer (Usual portion and Unusual portion) and the intramucosal propagations of extensively vertical type (EV) and nonextensively vertical type (NV). RESULT: 1) Tumor size, histological type, tumor location and intramucosal propagation type were significantly related to Ul., as the result of multivariate analysis. 2) The frequency of Ul. at the lesions of these cases, regardless of histological type, was higher at the lesion of Usual portion than at Unusual portion. And the frequency of Ul., independently of tumor location, was higher in Undiff. than in Diff.. 3) The frequency of Ul. at the lesions of Unusual portion in Undiff. was higher in EV than in NV. CONCLUSION: We suggested that extensively vertical propagation type of intramucosa, as well as large tumor size, Undiff. and at the lesion of Usual portion, was a significant risk factor for Ul. of the depressed type intramucosal cancer of the stomach. 2) We concluded that the intramucosal propagation type of the cancer was particularly concerned with Ul. at the intramucosal lesion of Unusual portion in Undiff.

Adult↗
PubMed2001

[Significance of nucleic acid extraction for the performance of COBAS AMPLICOR Mycobacterium-PCR assay].

On an AMPLICOR-PCR assay for the diagnosis of mycobacterial infections, it has been found that approximately 10% of the routinely performed assays appear as indefinable cases with internal control (IC)-negative, which is caused by contaminant PCR-inhibitory substances in the extracted nucleic sample. To decrease the number of indefinable cases, we studied the IC performance of four nucleic acid extraction methods in one manual method(A) and three commercial kits(B, C and D). Thirty samples from 10 kinds of specimens without mycobacterial infections were subjected to the four nucleic extraction methods and the nucleic extracts were compared on PCR-inhibitory. The frequency of IC-negative samples was different among the four methods and the rates were 33.3%(n = 10) in A, 30.0%(n = 9) in B, 16.7%(n = 5) in C and 6.7%(n = 2) in D. In the PCR-inhibitory experiments using serially diluted IC-negative samples, the recovery of IC positivity was also different according to the method used. Although the IC-negative nucleic samples by D method easily became IC-positive at the 1/5 range of dilution, some of the IC-negative nucleic samples by A, B or C method were still IC-negative in the 1/10 range. These results indicate that the occurrence rate of indefinable cases with IC-negative is markedly different in the nucleic extraction method, suggesting that utilizing a suitable nucleic acid extraction method is important when using the diagnostic AMPLICOR-PCR assay.

DNA, Bacterial↗
PubMed2001

[Clinical experience of intra-arterial chemotherapy for liver metastases of breast cancer patients].

The aim of this study was to evaluate retrospectively the effect of intra-arterial chemotherapy for liver metastases of breast cancer patients. Eleven patients treated between August 1991 and July 1997 at Keio University Hospital, Tokyo, Japan, were the subjects for this study. The duration of disease-free periods after the operation ranged from 9 to 78 months (median 27 months). The site of the recurrence was the liver alone in 6 cases, and the liver and lung in 1 case, bone in 1 case, lymph nodes in 2 cases, and a local region, in 1 case. The main drugs were adriamycin (ADM) and 5-fluorouracil (5-FU), administered in a single injection or continuously via an indwelling catheter in the hepatic artery. This method had a 36% response rate, including PR in 4 cases, NC in 3 cases and PD in 4 cases. The survival duration was 1 to 19 months (median 14 months) following this treatment, and 3 to 49 months (median 17 months) after the recognition of the recurrence. The only side effects of Grade 3 or 4 were leucocytopenia or granulocytopenia and nausea. These results suggest that intra-arterial chemotherapy for liver metastases of breast cancer patients may be an effective method for the control of liver metastases with minor side effects. However, further study may be necessary to establish methods to manage the indwelling catheter and to control patients with multiple metastases of the other organs, to improve the prognosis for recurrent breast cancer patients.

Adult↗