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Biomedical subjects

N Tamura

Publications and source records attributed to N Tamura.

At least 19 recordsLinked to original sources
PubMed2026

Eribulin versus taxane as first-line chemotherapy combined with dual HER2 blockade in patients with HER2-positive locally advanced or metastatic breast cancer: final survival outcomes of the JBCRG-M06/EMERALD study.

BACKGROUND: The phase III JBCRG-M06/EMERALD study was the first to show noninferior progression-free survival (PFS) of eribulin to taxane, combined with dual human epidermal growth factor receptor 2 (HER2) blockade (trastuzumab plus pertuzumab), as a first-line treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer (LABC/MBC). We report final survival outcomes and biomarker analyses of the EMERALD trial. PATIENTS AND METHODS: Patients with HER2-positive LABC/MBC were randomly assigned 1:1 to either eribulin or physician-choice taxane (docetaxel or paclitaxel), both combined with trastuzumab plus pertuzumab, as first-line chemotherapy. PFS and overall survival (OS) were assessed through 30 June 2023 for PFS and 31 December 2024 for OS. Survival outcomes were compared between the eribulin and taxane groups and according to circulating tumor DNA (ctDNA) detection of PIK3CA mutations (PIK3CAm+; E542K, E545K, H1047R, and N345K single nucleotide variants) or HER2 amplification (HER2 amp+; ERBB2 copy number >2.5). RESULTS: Median OS was 78.5 months [95% confidence interval (CI) 64.3-not reached (NR)] for eribulin and was NR for taxane, with a hazard ratio of 1.25 (95% CI 0.92-1.71, log-rank P = 0.19). The 60-month OS rates were 59.7% and 65.2% for eribulin and taxane, respectively. Median OS and 60-month OS rates were numerically lower in ctDNA PIK3CAm+ patients, and greater in ctDNA HER2 amp+ patients for all patients and with stratification by treatment group. There were no statistical interactions between treatment group with either ctDNA PIK3CAm or ctDNA HER2 amp status. Similar patterns were observed for PFS. CONCLUSION: Final survival analysis revealed that median OS exceeded 6 years with eribulin or physician-choice taxane, combined with trastuzumab plus pertuzumab, as first-line chemotherapy for HER2-positive LABC/MBC, with no significant differences between the two groups. ctDNA PIK3CAm+ status was a poor prognostic factor. ctDNA HER2 amp+ was associated with longer survival.

Aged↗
PubMed1992

Organization, structure, chromosomal assignment, and expression of the gene encoding the human endothelin-A receptor.

We have isolated and characterized the gene for the human endothelin-A receptor. Southern blot analyses demonstrated a single copy gene for the receptor. The gene spans more than 40 kilobases and contains eight exons and seven introns. Intron 1 exists in the 5'-noncoding region, and introns 2-7 occur in the coding region. The locations of introns 2-7 exist before or after the regions encoding the membrane-spanning domains. The transcription start site, determined by primer extension experiments, is 502 base pairs upstream of the methionine initiation codon. The 5'-flanking region lacks a typical TATA box but contains a potential SP-1-binding site 27 base pairs upstream of the transcription start site. Using human-rodent somatic hybrid cell DNA, the gene was assigned to human chromosome 4. Northern blot analyses revealed a 4.3-kilobase mRNA in a wide variety of human tissues, at the highest level in the aorta and at a substantial level in the cultured human mesangial cells. This is the first report of cloning of a gene for a member of the endothelin receptor family. The present study should give a clue to the discovery of possible disorders of the endothelin-A receptor, as well as facilitate the elucidation of the mechanisms by which the gene expression is regulated.

Amino Acid Sequence↗
PubMed1992

Selective reactivities of isocyanates towards DNA bases and genotoxicity of methylcarbamoylation of DNA.

The reactivities of methyl isocyanate (MIC) and phenyl isocyanate (PIC) with DNA, and the genotoxicity of MIC were investigated. MIC and PIC reacted with the exocyclic amino group of deoxycytidine, deoxyadenosine and deoxyguanosine to produce carbamoylated products. The reactions of both isocyanates with deoxycytidine were 2 and 4 orders of magnitude higher than with deoxyadenosine and deoxyguanosine, respectively. To explore the genotoxicity of MIC, M13mp9 RF DNA was modified with MIC and then introduced into E. coli. The plaque-forming efficiencies of DNA decreased with increasing dose levels, and the decreases were more pronounced in Uvr endonuclease-deficient strains (uvrA, uvrB and uvrC) than in the Uvr endonuclease-proficient strain, JM103. The differences in survival in JM103 and uvr- strains suggest that the methylcarbonyl adducts can be removed by the uvr excision-repair system. Modification of M13mp9 RF DNA with MIC induced MIC-dose-related, SOS-dependent mutations in the beta-galactosidase locus. These results demonstrate the genotoxic response of MIC-modified DNA in E. coli.

Carbamates↗
PubMed1992

Immunoadsorbent plasmapheresis for a patient with antiphospholipid syndrome during pregnancy.

The case of a 34 year old woman with systemic lupus erythematosus with a history of three previous recurrent abortions and lupus anticoagulant and anticardiolipin antibodies is reported. Immunoadsorbent plasmapheresis with a dextran sulphate column was used to remove lupus anticoagulant, anticardiolipin antibodies, and antibodies to DNA during her fourth pregnancy in combination with low doses of aspirin and prednisolone. Although during the course of treatment prednisolone was transiently increased to 30 mg/day owing to an asymptomatic increase of lupus anticoagulant and anticardiolipin antibodies, the levels of lupus anticoagulant, anticardiolipin antibodies, and antibodies to DNA were decreased by immunoadsorbent plasmapheresis and a baby girl was delivered successfully by caesarean section. Therefore, immunoadsorbent plasmapheresis with dextran sulphate seems to reduce the risk of recurrent abortion in patients with the antiphospholipid syndrome.

Adult↗
PubMed1992

Long-term cultured mouse mast cells: ultrastructure, histamine and leukotriene levels.

Interleukin 3 (IL3), dependent cells were obtained from bone marrow (9/10 experiments) and spleen cells (4/5 experiments), but not from the thymus. These cells were similar to mucosal mast cell toluidine blue staining and electron microscopy. They had heterogenous metachromatic granules, and some had large scroll-like structures. They also contained histamine (200-800 ng/10(6) cells) for the first 2-5 weeks, whose level diminished to less than 30 ng/10(6) cells by 10 weeks of culture. They also generated leukotriene (LT) C4/D4 (10-40 ng/10(6) cells) and LTB4 (2-5 ng/10(6) cells) for over 100 days of culture. In one experiment, bone marrow-derived mast cells after 150 days of culture began to produce an IL3-like substance and proliferated exponentially without exogenous IL3.

Animals↗
PubMed1992

Synthesis and glutamate-agonistic activity of (S)-2-amino-3-(2,5-dihydro-5-oxo-3-isoxazolyl)-propanoic acid derivatives.

(S)-2-Amino-3-(2,5-dihydro-5-oxo-3-isoxazolyl)propanoic acid, (3a) and its analogs (3b--h) were prepared and evaluated for glutamate receptor-agonistic and antifungal activities. Several (S)- and (R)-2-amino-3-isoxazolylpropanoic acid derivatives (3a--d) were synthesized starting with (S)- and (R)-N-tert-butoxycarbonyaspartic acid alpha-methyl esters (4, n = 1) by means of Masamune's chain extension reaction followed by isoxazolone formation with hydroxylamine and subsequent deprotection reactions. Furthermore, (S)- and (R)-N-tert-butoxycarbonylglutamic acid alpha-methyl esters (4, n = 2) were converted to (S)- and (R)-2-amino-4-isoxazolylbutyric acid derivatives (3e-h) via the same sequence of reactions.

Antifungal Agents↗
PubMed1992

Bond strengths of various materials to dentin using Amalgambond.

This study evaluated the bond strength of four restorative materials to dentin using Amalgambond. Two high-copper amalgams [Tytin; spherical, (T) and Epoque 80; lathe-cute, (E)], a gallium alloy [Gallium Alloy GF (G) and a resin composite [P-50 (P)] were tested. The polished dentin surface was treated with dentin-enamel activator (10 seconds), washed, dried, and adhesive agent was applied (30 seconds). In group A, the dentin adhesive was placed onto the dentin and while still wet, T, E, or G was condensed in cylinders (4 mm diameter) with condensation forces suggested by the manufacturer for a clinical situation. In group B, the cylindrical specimens of restorative material were allowed to set and then adhered to the treated dentin using the adhesive system. For the composite (control), the adhesive was applied to the treated dentin and while still wet, P was layered into the cylinder and cured for a total of 90 seconds. After storage in water (37 degrees C) for 24 hours, all the specimens were tested for tensile bond strength. This study revealed that the bond strength of P was significantly higher than the other materials tested and also that amalgam allowed to set for 1, 6 or 24 hours before adhesion to dentin had a significantly greater bond strength than freshly condensed amalgam. Although the desired high bond strength did not develop in the bonding of the metallic restorative materials, signs of bonding were found.

Analysis of Variance↗
PubMed1992

[Diversity of T-cell antigen receptor response in individuals with sarcoidosis].

T-lymphocytes recognize specific antigen(s) through T-cell antigen receptors (TCRs). There are two classes of TCRs: those composed of alpha beta chain dimers and those formed by gamma delta dimers. Although the pathogenesis of sarcoidosis is still unclear, participation of exogenous antigen(s) is highly suggested. To investigate the mechanism of activation and accumulation of T-lymphocytes at the sites of disease, the bias of TCRs in individuals with sarcoidosis was evaluated with respect to several points. Eighteen of 51 cases of sarcoidosis showed increase of gamma delta-TCR positive T-lymphocytes in the blood. In contrast to the blood, a low number of gamma delta T-cells and evidence of T-cell stimulation through alpha beta-TCR were observed in the lung. The TCR junctional regions of V gamma 9, V delta 2 and V beta 8 gene segments were sequenced from blood and lung T-cells of individuals with sarcoidosis and normal subjects, using RT-PCR. In normals, a huge diversity of the junctional region sequences was observed in V gamma 9, V delta 2 and V beta 8 transcripts in the blood and lung. In contrast to normal subjects, a subgroup of sarcoidosis showed an increase of V gamma 9 transcripts sharing identical sequences. Although less marked than for V gamma 9, an increase in identical junctional region sequences was also observed in V delta 2 transcripts. All junctional region sequences of V beta 8 transcripts in the blood and lung were unique, indicating polyclonal activation of T-cells through TCR beta-chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

[A case of hypersensitivity pneumonitis due to isocyanate exposure showing progression even two months after removal of the antigen].

A 68-year-old male developed dry cough and exertional dyspnea after handling paint spray containing isocyanates (TDI, MDI) for three months. Initially, the symptoms fluctuated according to whether he was at work or not. He was admitted to our hospital on February 7, 1990, because of progressive worsening of symptoms. In spite of admission to hospital and cessation of exposure to isocyanates, there was no improvement of symptoms. His chest X-ray film showed diffuse small nodular and reticular shadows. Transbronchial lung biopsy revealed thickening of the alveolar walls and formation of Masson's bodies associated with mononuclear cell infiltration in alveolar spaces. High titers of TDI-HSA and MDI-HSA specific IgG antibodies were detected by ELISA, and a high level of serum soluble IL2 receptor was also detected. From these results, we diagnosed hypersensitivity pneumonitis due to exposure to isocyanates. One week administration of prednisolone caused dramatic improvement of his symptoms, chest X-ray findings, and laboratory data. His clinical course and response to prednisolone therapy indicated that long-term steroid administration could not be avoided. The prolonged symptoms and the necessity for long-term steroid therapy are discussed.

Aged↗
PubMed1992

[A case of mediastinal lymphatic cyst possibly originating from the right thoracic duct].

A 33-year-old male was admitted to our hospital because of an abnormal shadow in the right superior mediastinum on chest X-ray, which was first noted about half a year before his admission. Several diagnostic procedures, including fiber bronchoscopy, CT scan and MRI; however, no final diagnosis could be made. Thoracotomy was performed with the presumed diagnosis of benign mediastinal cystic tumor. Entry of the right thoracic duct into the cyst was observed at operation. Histological examination revealed that the cyst was lined by mono-layered cuboidal epithelial cells with lymphocytic infiltration in the wall of the cyst. The mono-layered cuboidal epithelium of the thoracic duct gradually changed to the epithelium of the cyst. Twenty ml of colorless transparent fluid was aspirated from the cyst. Analysis of aspirated fluid revealed low concentration of several substances except LDH compared to the values of the previously reported normal standards and other reported cases. From these findings, the cyst was diagnosed as mediastinal lymphatic cyst. Entry of the thoracic lymphatic duct into the mediastinal lymphatic cyst is a rare occurrence, and it is of interest to speculate on its relationship to the origin of the lymphatic cyst.

Adult↗
PubMed1992

[Surgical treatment of dissecting aortic aneurysm using GRF glue].

A 62-year-old woman underwent primary anastomosis for dissecting aortic aneurysm (DeBakey IIIb) using GRF glue. GRF glue consists of mixture of gelatin and resorcin. The mixture is hardened by the addition of medical formaldehyde. Resorcin is diphenole which reacts with formaldehyde, creating tridimentional network. Primary anastomoses were performed after the lumen of dissected aorta was adhered with GRF glue. It appears that primary anastomosis using GRF glue is a simpler and safer operative method for dissecting aortic aneurysm.

Anastomosis, Surgical↗
PubMed1992

[Clinical experience of sternal retractor for dissection of internal thoracic artery].

We performed dissection of internal thoracic artery using sternal retracor for I.T.A. made by Delacroix Chevalier in France. This retractor composed of 5 elements i.e. arms, cranking axe, two assymetric claws and assymetric valve. This retractor is entirely reversible, so the same apparatus is used for left and light dissections. We concluded that this retractor has minimal risk to internal organs and the best position for exposure of I.T.A.

Dissection↗
PubMed1991

A novel glutamate agonist, TAN-950 A, isolated from streptomycetes.

A novel antifungal amino acid antibiotic, TAN-950 A ([S]-2-amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid), was found to have affinity for three excitatory amino acid (EAA) receptors and to inhibit [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), [3H]kainate and [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) binding competitively. It caused excitation of rat hippocampal CA1 neurons in vitro, an effect that was antagonized by an AMPA/kainate antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX). Chemical modification of TAN-950 A brought about a large change in its pharmacological activity. Alkylation at the C-3 position of the isoxazolone ring markedly increased the ability to elicite neuronal firing. This agonistic effect was also antagonized by DNQX. The (R) enantiomer of TAN-950 A had increased selectivity for the N-methyl-D-aspartate (NMDA) receptor subtype. This selectivity was further enhanced by removal of the methylene group from the amino acid moiety. The most potent NMDA agonistic activity was observed with [R]-2-amino-2-(2,5-dihydro-3-methyl-5-oxo-4-isoxazolyl)acetic acid. These derivatives of TAN-950 A might be useful agents for investigating the pharmacological and physiological roles of EAA receptors.

Animals↗
PubMed1991

[A case of fibrous dysplasia (McCune Albright syndrome) associated with acromegaly].

We report a case of a 47-year-old woman with McCune-Albright syndrome associated with unusual growth-hormone and prolactin hypersecretion. Acromegaly was suspected on clinical examination, and she was referred to us. She had no history of precocious puberty or pathological fracture. She was 154cm tall, weighing 62kg with so-called acromegalic facies. There were two lumps, one of which was on her right lateral forehead. The other on the right lower extremity seemed to be due to a bone deformity. Some brown pigmented macules with irregular borders were present on her lips and oral mucosa. Endocrine examination revealed elevated basal levels of plasma GH (54ng/ml) and PRL (36.2ng/ml), which paradoxically increased after injection of TRH. Plasma levels of these hormones did not change after LHRH test, and plasma GH level increased after GHRH test. A skull X-ray film showed a double floor of the sella turcia and hyperostotic formation of the right sphenoid bone. MRI and CT showed a tumor shadow in the right sella turcica. Bone roentogenography of the right fibula and tibia showed a large centrally expanding lesion with a ground-glass or cystic appearance and a thin cortex. The left fibula showed a similar lesion. We recognized similar findings in other bones which also showed abnormal accumulation in a radionuclide bone scan with 99mTc. On the basis of physical, endocrinological and roentogenographical examination, we diagnosed her as displaying McCune-Albright syndrome. We operated on her by transsphenoidal surgery and confirmed a functioning chromophobe adenoma which was removed during surgery. She has been free of GH and PRL hypersecretion since then. The pathology of the sphenoidal sinus affected with fibrous bone was in accordance with the findings of fibrous dysplasia. McCune-Albright syndrome (MCAS) is known as a syndrome characterized by polyostotic fibrous dysplasia and cutaneous pigmentation and multiple endocrinopathy. Its etiology is unknown. This syndrome with acromegaly is rare, and although 26 cases have been described in literature, pathological examinations have been undertaken in only three cases. This case was very rare and valuable because, by operating on her by the transsphenoidal route in spite of the sphenoidal sinus being affected with fibrous bone, we were able to confirm a chromophobe adenoma secreting both GH and PRL. We recognized that acromegaly with MCAS was endocrinologically, morphologically and immunohistologically the same as acromegaly without MCAS. Therefore, we concluded that acromegaly with MCAS is much the same as acromegaly without MCAS.

Acromegaly↗
PubMed1991

Exercise-entrained breathing and non-invasive determination of anaerobic threshold.

Incremental cycle exercise was performed by 17 subjects under two breathing conditions: spontaneous breathing (Non-ENT run) and deliberate entrainment of breathing frequency (f) to cycling rate at preferred coupling ratios up to possibly high work rates (ENT run). The purpose was to investigate the influence of entrainment on two non-invasive determinations of anaerobic threshold (AT): the break points of VE/VO2 (VAT) and VCO2 (V-slope AT) changes against VO2. Compared to the Non-ENT run, VAT in the ENT run was greater in 12 subjects entrained at higher f accompanied by relative hyperventilation at low work rates, while it was similar in five subjects entrained at lower f accompanied by relative hypoventilation. Relative hyperventilation and hypoventilation during the ENT run tended to elicit greater and lower VCO2, respectively, relative to VO2, as compared to the Non-ENT run. These different VCO2, responses between the two runs exerted little influence on the V-slope AT determination. It is concluded that breathing patterns and ventilatory response during incremental work tests can affect the VAT method but not the V-slope method.

Adult↗
PubMed1991

Preferential usage of the T-cell antigen receptor beta-chain constant region C beta 1 element by lung T-lymphocytes of patients with pulmonary sarcoidosis.

Evaluation of the T-cells accumulating at sites of disease in active sarcoidosis suggests the accumulation process is not random, evidenced by a bias in the types of T-cells present. To evaluate the concept that this bias extends to the accumulation of T-cells with the preferential use of specific T-cell antigen receptor (TCR) beta-chain constant region elements, beta-chain mRNA transcripts of lung and blood T-cells of normal subjects and patients with pulmonary sarcoidosis were compared for the relative usage of constant region beta 1 or beta 2 elements. Quantitative evaluation of C beta 1 and C beta 2 mRNA transcripts demonstrated a C beta 1/C beta 2 usage in normal blood of 0.63 +/- 0.02, similar to that of normal lung (0.64 +/- 0.06, p greater than 0.7), and in sarcoid blood (0.59 +/- 0.03, p greater than 0.2). In contrast, the lung T-lymphocytes of patients with sarcoidosis reflected a marked bias in the usage of C beta 1 elements (C beta 1/C beta 2: 0.88 +/- 0.06, p less than 0.001 compared with sarcoid blood and normal blood; p less than 0.02 compared with normal lung). Interestingly, a subgroup of these patients (six of 18) showed a markedly exaggerated skewing in the use of C beta 1 elements (C beta 1/C beta 2 ratio greater than 1, i.e., greater than 3 standard deviations above mean), demonstrating heterogeneity among sarcoid patients with regard to specific C beta 1 usage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗