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Biomedical subjects

T Hachiya

Publications and source records attributed to T Hachiya.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Prostatectomy for prostate cancers].

Radical prostatectomy may afford cure in men in whom the malignancy is completely extirpable. Historical experiences as well as ours agreed that long term survival after radical prostatectomy was excellent if the disease was confined to the organ. Cure may also be expected in some selected patients with minimal extra-organ invasion. Furthermore, preoperative hormonal therapy may improve the cure rate in these invasive diseases. However, if cure means affording the patient the best chance of dying of some causes other than cancer, some of those extirpable diseases may be cured without surgery. This idea was supported by epidemiologic data on the natural history of the disease, and retrospective observations of conservatively treated patients. Challenging issues toward the 21st century are to expand the range of surgically curative diseases, and to identify diseases extirpable but predestined never to kill the host during the natural course of his life.

Aged↗
PubMed1998

[Clinical staging of prostate cancer].

Clinical staging of prostate cancer was reviewed on the basis of TNM classification edited by UICC in 1997. In this revision, (1) T1c was newly categorized among T1 for cases of high PSA level without any abnormal sign of DRE, (2) T2 was subdivided into T2a and T2b in accordance with unilateral or bilateral nodule in the prostate, respectively, (3) T3 was also subdivided into T3a with capsular invasion and T3b with seminal vesicle invasion. It is hoped that present classification will become useful tools for the detection of the tumor burden cancer patients.

Humans↗
PubMed1998

[A study on androgen deprivation therapy prior to radical prostatectomy with special reference to the tumor volume].

BACKGROUND: The aim of this study is to analyze correlation between the tumor volume (TV) and the final pathological stage in patients undergoing neoadjuvant therapy. PATIENTS AND METHODS: Twenty-six patients underwent radical prostatectomy alone (group S). The remaining 28 patients had undergone neoadjuvant therapy (group N) which mainly consisted of LH-RH agonist. TV and the final pathological stage were retrospectively reviewed. RESULTS: The likelihood of positive surgical margin was statistically higher in group S than in group N (p = 0.009). The correlation between TV and the pathological stage was observed not only in group S (rho = 0.646, p = 0.0012) but also in group N (rho = 0.716, p = 0.0002). The mean TV was statistically smaller in group N in patients with baseline PSA level more than 10.1 ng/ml (p = 0.024). CONCLUSION: A decrease in tumor volume caused by neoadjuvant therapy may play an important role in reducing the likelihood of positive surgical margin.

Antineoplastic Agents, Hormonal↗
PubMed1998

[A case of paragonimiasis westermani].

A 45-year-old man, who had eaten fried fresh water crabs (Geothelphusa dehaani), was admitted to our hospital because of productive cough and bloodysputum. Blood chemistry showed increased levels of white blood cells and C-reactive protein, but peripheral blood eosinophil counts and serum IgE values were not elevated. Chest roentgenogram and chest computed tomographic scan revealed infiltration of the right middle and left upper lung fields. He was diagnosed as having pneumonia, but his symptoms and radiological examination findings did not improve with antibiotics. The diagnosis of paragonimiasis was confirmed by immunoserological examination and detection of ova in sputum, stool and bronchoalveolar lavage fluid samples. Transbronchial lung biopsy showed infiltration and degranulation of eosinophils. The patient was treated with praziquantel for 3 days at a daily dosage of 75 mg/kg. After uneventful completion of treatment all clinical symptoms and radiological abnormalities disappeared. This is the first case in which ova of paragonimiasis westermani were identified in Nagano prefecture.

Adult↗
PubMed1997

Contribution of enhanced transcriptional activation by ER to [12Val] K-Ras mediated NIH3T3 cell transformation.

We investigated the biological significance of estrogen receptors (ER) in NIH3T3 cell transformation by the [12Val] K-Ras mutant. This mutant enhanced the steady state level of ER. Cells expressing mutant K-Ras (K12V cell) were tumorigenic. To determine the role of ER accumulation in Ras-transformed cells, we developed cells (KwtER cells) that overexpressed both wild-type (wt) K-Ras and ER, and found these cells were also tumorigenic. E2 stimulated the transcriptional activity by ER dominantly in K12V cells. However, only partial activation of ER by E2 was seen in KwtER cells. In the presence of 10% serum in media, the activation of ER appeared only in transformed KtwER and K12V cells, suggesting that two independently transmitted signals, the E2-ER binding and the ER-AF1 activation, are necessary for ER activation and that the dominant activation of ER might be involved in Ras-mediated cell transformation. Co-expression of progesterone receptor (PR) with mutant K-Ras led to suppression of tumorigenicity and inhibition of the activation of ER. The antisense oligomers complementary to the ER suppressed proliferation and transformed phenotypes of K12V cells. These observations support the importance of ER in Ras-mediated cell transformation.

3T3 Cells↗
PubMed1997

Identification of a novel nuclear speckle-type protein, SPOP.

A novel antigen recognized by serum from a scleroderma patient was identified by expression cloning from the HeLa cell cDNA library. The cloned cDNA encoded a 374-amino acid protein with a relative molecular mass of 47,000 and a predicted amino acid sequence 62.7% identical to the hypothetical protein of Caenorhabditis elegans, T16H12.5. The deduced amino acid sequence had a typical POZ domain and an unidentified region conserved during evolution. No zinc finger or RNA recognition motifs were found in this clone. The 2 kbp mRNA encoding the novel clone SPOP (speckle-type POZ protein) was found to be expressed in all human tissues examined. HA-tagged SPOP, transfected and overexpressed in COS7 cells, exhibited a discrete speckled pattern in the nuclei and was co-localized with the splicing factor, snRNP B'/B. Deletion analysis revealed that both the POZ domain and the evolutionarily conserved region at the amino-terminus are required for the nuclear speckled accumulation of SPOP.

Amino Acid Sequence↗
PubMed1997

Expression of a neutrophil chemotactic protein LECT2 in human hepatocytes revealed by immunochemical studies using polyclonal and monoclonal antibodies to a recombinant LECT2.

A recombinant human neutrophil chemotactic protein LECT2 (rhLECT2) was purified as a 16-kDa protein from the culture fluids of stable transfectants derived from CHO cells (clone C1D8-1) and L929 cells (clone L2E4-1). The N-terminal amino acid sequence of the protein secreted by both clones were homologous to the previously described bovine LECT2. We produced polyclonal and monoclonal antibodies against rhLECT2 and investigated secretion of LECT2 protein in six human hepatoma cell lines, which express LECT2 mRNA, and in hepatocytes of normal human livers by a sandwich enzyme-linked immunosorbent assay and by immunostaining using the antibodies, respectively. We revealed that five of six hepatoma cell lines secreted LECT2 into culture fluids at concentrations of 30-135 ng/mg. We also demonstrated that the cytoplasm of human hepatocytes was diffusely stained, although periportal hepatocytes tended to be weakly and granularly stained by immunostaining. These results indicated that the novel protein was expressed in hepatocytes and suggested an important role of LECT2 in the cells in addition to the activation of neutrophils.

Animals↗
PubMed1997

Predominant expression of the src homology 2-containing tyrosine phosphatase protein SHP2 in vascular smooth muscle cells.

src homology 2 (SH2)-containing protein-tyrosine phosphatase SHP2 is known to transduce positive signals from activated receptor protein-tyrosine kinases such as platelet-derived growth factor receptor (PDGFR) beta and insulin receptor. Here, we demonstrate the physiological expression of SHP2 in rats. In northern and western blot analyses, SHP2 expressions were recognized in all tissues, but their expression levels varied significantly among tissues: it is lowest in the liver and kidney. Immunohistochemical staining and in situ hybridization showed SHP2 was expressed ubiquitously but predominantly in vascular smooth muscle cells (SMC). During the development of granulations. SHP2 was expressed predominantly in vascular SMC and also highly expressed in capillary cells. The functional associations of SHP2 with PDGFR beta, which transduces major growth signals in vascular SMC, identify a crucial function of SHP2 in blood vessels in consert with PDGFR beta.

Actins↗
PubMed1997

Direct hepatic vein anastomosis during hepatectomy for colorectal liver metastases.

BACKGROUND: When the right and middle hepatic veins (RHV and MHV) and all the short hepatic veins are removed during resection of segments (S) 7 and 8 and part of S 5 and 6 including the caudate lobe, the remainder of S 5 and 6 shows congestion, so restoration of liver function may be delayed. METHODS: In 5 patients with hepatic metastases of colorectal carcinoma, which were in the region circumscribed by the RHV, MHV, and inferior vena cava, direct hepatic vein anastomosis was performed during hepatectomy. RESULTS: Hepatic vein reconstruction took 17 to 30 minutes to complete. All 5 patients had an uneventful postoperative course, and the anastomosis was patent at 1 month after operation. One patient died of recurrent carcinoma 6 months after operation. Four have remained alive and disease free for 12, 24, 40, and 61 months. CONCLUSION: Direct hepatic vein anastomosis is an option, which should be adopted in hepatectomy, especially in patients with carcinoma invading the major hepatic veins and short hepatic veins.

Aged↗
PubMed1997

Demonstration of thyroid stimulating activity within H chain fragments of TSAb-IgG by protease digestion and reduction.

OBJECTIVE: Whether or not the distribution of biologically active fragments in TSAb-IgG molecules parallels antigen-binding activity in other anti-thyroidal antibodies was examined. DESIGN: Both the thyroid stimulating (TS) activity (cAMP production in thyroid cells) and TSH binding inhibition (TBI) activity (determined by TSH receptor assay) were examined by measuring the reduction in TSAb-IgG followed by gel-filtration on Sephadex G-100. Two forms of IgG [IgG(kappa) and IgG(lambda)] were separated from TSAb-IgG by column chromatography using Protein L-Sepharose (specifically binds to kappa chain). The IgG(kappa) was reduced with dithiothreitol (DTT) and the unbound fraction (UF) (the free heavy (H) chain) and the bound fraction (BF) (the free kappa chain and the non-reduced IgG(kappa)) were separated using Protein L-Sepharose. The Fab fragment was separated by Protein A-Sepharose after papain hydrolysis of TSAb-IgG, then separated into two Fab(kappa) and Fab(lambda) forms by Protein L-Sepharose. The Fd fragment (or fragment containing Fd) was prepared from Fab(kappa) by DTT reduction followed by Protein L column. RESULTS: The free H chain fraction showed TS and TBI activity, but neither anti-thyroglobulin (Tg) nor anti-thyroid peroxidase (TPO) antibody activities. The free light (L) chain was not biologically active. Similar TS and TBI activities were found not only in IgG(kappa) and IgG(lambda) but also in the Fab(kappa) and Fab(lambda) fractions. Fd fragment that was not contaminated with free kappa chain had TS and weak TBI activities. CONCLUSIONS: The thyroid stimulating activity in 5 TSAb-IgG samples was found in IgG(kappa), IgG(lambda), Fab(kappa), Fab(lambda), H chain and Fd separated by papain digestion and reduction. These results showed that TSAb was polyclonal and that the Fd fragment was important as the biologically active site.

Chromatography↗
PubMed1997

Demonstration of fragments with thyroid stimulating activity from thyroid stimulation blocking antibodies-IgG molecules by papain digestion.

OBJECTIVES: Thyroid stimulation blocking antibodies (TSBAb) inhibit TSH action and may have a role in the pathogenesis of hypothyroidism. In order to study the relationship between blocking and stimulating activities we have examined the biologically active fragments in TSBAb-IgG molecules after papain digestion. DESIGN: Both thyroid stimulating (TS) activity (cAMP production in thyroid cells) and TSH binding inhibitory (TBI) activity (determined by TSH receptor assay) in sera from patients with primary hypothyroidism were examined after digestion with papain-Sepharose in the presence of cysteine. The digested IgG was separated into unbound (UF) and bound (BF) fractions on a Protein A-Sepharose column. Each fraction was then gel-filtrated on a Sephadex G-100 column. RESULTS: TS activity was found within one hour after hydrolysis in 5 out of 7 antibodies, then gradually decreased after more prolonged incubation. Both TS and TBI activities in the UF and the BF from Protein A were found in Feb (Mr 50 kD) and the second protein peak (Fc with trace amounts of Fab), respectively. The biological activity in the second protein peak was suggested as being derived from Fab fraction, because the activity bound to the anti-F(ab')2 column. However, the first peak (undigested IgG) in the BF had neither TS nor TSB activity. The TS activity in the retarded fraction (less than Mr 20 kD) in the UF gradually increased with prolonged digestion. CONCLUSIONS: The conversion of Thyroid stimulation blocking antibodies activity to thyroid stimulating activity by papain digestion suggests that the inherent thyroid stimulating activity located in the Fab portion of the IgG molecule is unmasked by papain cleavage. We also suggest that the thyroid stimulating activity in the retarded fraction in the unbound fraction may be released from hydrolysis of the Fab portion of the IgG molecule.

Antibodies, Blocking↗
PubMed1997

Calmodulin purified from human and porcine thyroids inhibits thyrotropin binding to porcine thyroid cells.

A thyrotropin (TSH) binding inhibiting protein (TBIP) that inhibits TSH binding to the TSH receptor, as determined by the TSH receptor assay, was purified from human and porcine thyroid. The soluble fraction (100,000 x g supernatant of Graves' thyroid homogenate) was precipitated with ammonium sulfate between 1.75 to 2.5 mol/L. TBIP was eluted by 0.5 mol/L sodium chloride (NaCl) containing 20 mmol/L Tris buffer, pH 7.5 from a Q-sepharose column. The unbound fraction from concanavalin A (Con A) and blue-sepharose was gel-filtered using sephadex G-100, and finally purified by Resource Q column chromatography. Purified TBIP was confirmed as a single protein band of 17 kDa. The TBI activity in the purified TBIP was significantly decreased by either etnylene glycol tetraacetate (EGTA) (1 mmol/L) or antibody to calmodulin (CaM) in the TSH receptor assay. The TBIP was confirmed immunologically as CaM by the Ouchterlony method using antibody for CaM. These findings demonstrated that the TBIP purified from human and porcine thyroids was, in fact, CaM. We examined the effects of TBIP purified from human thyroid on bovine TSH (bTSH) or thyroid stimulating antibody (TSAb)-stimulated cyclic adenosine monophosphate (cAMP) production in porcine thyroid cells (PTC). TBIP itself did not increase basal levels of cAMP production, but inhibited bTSH (100 mU/L)-stimulated cAMP production. However, TBIP did not inhibit cAMP production stimulated by TSAb-IgG and various thyroid stimulators (GTPgammaS, forskolin and pituitary adenylate cyclase-activating polypeptide [PACAP, 27 and 38 amino acids]). Authentic CaM purified from bovine brain behaved in a manner similar to that of TBIP. These data showed that CaM differentially affects thyroid stimulation by TSH and TSAb in intact thyroid cell experiments.

Animals↗
PubMed1997

Inhibition by anti-RCC1 monoclonal antibodies of RCC1-stimulated guanine nucleotide exchange on Ran GTPase.

Nine monoclonal antibodies to RCC1, the guanine nucleotide exchange factor on Ran GTPase, were obtained using recombinant RCC1 as the antigen. Epitopes of three monoclonal antibodies, which did not inhibit RCC1 function, were localized in the N-terminus outside the RCC1 repeat, while epitopes of the other 6 monoclonal antibodies were localized within the RCC1 repeat. Three of the latter 6 monoclonal antibodies, 2B6, 6C3, and 8D9, inhibited RCC1-stimulated nucleotide release. Two of them, 2B6 and 6C3, recognized the same amino acid residues in the N-terminus of the second RCC1 repeat, Tyr89, Ser90, Phe91, and Gly92, of which one, Gly92, is conserved in Saccharomyces cerevisiae and mutated in an rcc1(-) strain, mtr1-2. The monoclonal antibody 8D9 recognized two amino acid residues, Arg320 and Ala321, downstream of Gly319 in the N-terminus of the 6th RCC1 repeat, which corresponds to Gly92 in the second RCC1 repeat. The monoclonal antibodies which inhibited RCC1 function bound to RCC1 in homogeneous solution and stained cellular RCC1. We propose that the N-terminus of the RCC1 repeat is exposed at the surface of RCC1 on the coated plate or in fixed cells, and is involved in the RCC1-stimulated nucleotide exchange on the Ran GTPase.

Amino Acid Sequence↗
PubMed1997

Significance of prostate-specific antigen after radical prostatectomy.

BACKGROUND: Serum prostate-specific antigen (PSA) is expected to be undetectable after radical prostatectomy unless there is residual disease or disease progression. The aim of this study was to confirm the usefulness of serum PSA measurements in monitoring patients after radical prostatectomy. METHODS: We conducted a study of 50 patients who underwent radical prostatectomy for clinical stage T1-2 or small T3 prostate cancer, analyzed serum PSA levels before and after surgery and compared the pathological findings and clinical outcome. RESULTS: Postoperative PSA elevation (PSA failure) was noted in 13% of patients with organ-confined disease (OCD), 43% with positive surgical margins and/or seminal vesicle involvement (PSM/SVI), and 60% with positive lymph nodes (N+). Postoperative clinical failure was noted in 8 patients, and all were preceded by PSA failures. The 3-year PSA failure-free rates were 86.5%, 32.1%, and 40.7% and the 3-year clinical failure-free rates were 100%, 67.5%, and 73.5% in patients with OCD, PSM/SVI and N+, respectively. CONCLUSION: An elevation of serum PSA levels after radical prostatectomy was a sensitive indicator of persistent disease after surgery, and preceded clinical manifestations of disease progression.

Aged↗
PubMed1997

Significance of the BTA test in bladder cancer: a multicenter trial. BTA Study Group Japan.

BACKGROUND: The BTA test is a latex agglutination assay for the qualitative detection in the urine of analytes that are associated with bladder tumor. We compared the results of the BTA test with those of voided urine cytology (VUC) in patients with bladder cancer. METHODS: A multicenter trial was performed at 6 institutions. A total of 132 patients with histologically diagnosed bladder cancer were enrolled. Urine samples were split for BTA and VUC testing. RESULTS: The sensitivities of the BTA test and VUC were 57.6% and 37.9%, respectively; this difference was significant (P < 0.001). The BTA test had much higher sensitivity for small, solitary, superficial tumors than did VUC. CONCLUSION: The BTA test is simple to perform, gives rapid results, and is far more sensitive than VUC for detection of bladder cancer. The BTA test has the potential to become an additional tool for detecting bladder cancer.

Adult↗
PubMed1997

[Impact of androgen deprivation prior to radical prostatectomy for T1, T2 prostate cancer on the likelihood of curative surgery].

BACKGROUND: Extracapsular extension is commonly seen in patients undergoing radical prostatectomy for localized prostate cancer due to understaging of disease. One possible approach to reduce the likelihood of extracapsular disease is androgen deprivation prior to radical prostatectomy, neoadjuvant therapy. However, adequate application is not clear. We analyzed the outcome of neoadjuvant therapy and radical prostatectomy in an attempt to expand our understanding on indications of neoadjuvant therapy. METHODS: Forty-six selected patients with clinical T1 or T2 prostate cancer were retrospectively reviewed. Twenty-two patients underwent neoadjuvant therapy (group N) that mainly consists of LH-RH agonist. The duration of neoadjuvant therapy, varied from 1 to 12 months with the mean being 4 months. Twenty-four underwent radical prostatectomy alone (group S). RESULTS: In the group N and group S, 59% and 33% had either organ confined disease (OCD) or specimen confined disease (SCD) respectively. When the patients had OCD or SCD, they were defined as surgically cured patients. In the patients with clinical stage T1b, T1c, and T2 disease, likelihood of surgical cure were 100%, 50%, 46.7% in group N, 100%, 20%, 11%, in group S respectively. In the patients with initial serum PSA less than 10 ng/ml and more than 10.1 ng/ml, likelihood of surgical cure were 83.3% and 50% in group N, 63.6% and 15.4% in group S, respectively. Likelihood of surgical cure was higher in the patients with well differentiated carcinoma both in group N and group S. All the patients with serum PSA less than 0.1 ng/ml after neoadjuvant therapy had OCD. CONCLUSION: Neoadjuvent therapy could be beneficial either in the patients with moderately or in the poorly differentiated adenocarcinoma of prostate especially in the group with initial serum PSA more than 10.1 ng/ml. However, in patients both with well differentiated adenocarcinoma and the initial serum PSA less than 10 ng/ml, no evidence of beneficial effect on the likelihood of OCD or SCD was observed. PSA after neoadjuvant therapy could be useful predictor for the pathological outcome.

Aged↗
PubMed1997

Technetium-99m-ECD brain SPECT in misery perfusion.

UNLABELLED: Discordant findings of 99mTc-methyl cysteinate dimer (99mTc-ECD) brain distribution have been reported when brain tissue is supplied by excess blood flow. We evaluated changes in 99mTc-ECD brain activity in the opposing pathological state, in which cerebral blood flow (CBF) is more profoundly impaired than metabolism, and analyzed the relationship of 99mTc-ECD activity with CBF and metabolism to investigate the dominant regulating factor on 99mTc-ECD distribution. METHODS: Twelve patients with unilateral intracranial steno-occlusive diseases were evaluated using dynamic and static 99mTc-ECD SPECT. Relative 99mTc-ECD activities and the retention ratio of the affected and unaffected cortices were compared with CBF and oxygen metabolism obtained by PET. Change in the relationships until 1 hr after tracer injection were also analyzed. RESULTS: Relative 99mTc-ECD activity was significantly correlated with CBF, and the highest correlation was obtained for the first minute of imaging (r = 0.674, p < 0.0010. Fifteen minutes after injection, the correlation coefficient with CBF decreased, whereas higher correlation was observed with the parameter of oxygen metabolism (r = 0.758-0.815, p < 0.001). Changes in the retention ratio were dependent on changes in oxygen metabolism, and the retention ratio for the high oxygen extraction fraction (OEF) area was the same as that for the normal OEF area. CONCLUSION: In addition to CBF, brain distribution on 99mTc-ECD SPECT images is affected by brain metabolism, especially on delayed images after injection. The degree of discrepancy between CBF and metabolism should be considered when interpreting images of the misery perfusion state.

Blood-Brain Barrier↗