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Biomedical subjects

T Fujikawa

Publications and source records attributed to T Fujikawa.

At least 55 records · Page 3Linked to original sources

20 kDa human growth hormone (20K hGH) stimulates insulin-like growth factor-I (IGF-I) gene expression at lower concentrations than 22K hGH in hGH receptor-expressing Ba/F3 cells.

Growth hormone (GH) secreted from the pituitary is essential for postnatal growth in animals. GH exerts its actions by a direct effect on target organs and by stimulating insulin-like growth factor I (IGF-I) production. In the human pituitary, there is a naturally occurring variant protein which has a molecular mass of 20 kDa (20K hGH) besides the major 22 kDa hGH (22K hGH), but the physiological actions of 20K hGH are still poorly understood. In this study we have examined its effects on the IGF-I mRNA expression in the pro B-cell line Ba/F3 cells stably expressing hGH receptor (Ba/F3-hGHR). Ba/F3-hGHR cells were incubated for 2 h with a series of various concentrations (10 pM to approximately 10 nM) of 20K or 22K hGH. The IGF-I mRNA expression in the Ba/F3-hGHR cells was detected by the RT-PCR method. IGF-I gene expression was increased by 20K and 22K hGH stimulation, but not by PRL or IL-3 in the Ba/F3-hGHR. And this effect was not observed in parental Ba/F3 cells. Lower concentrations of 20K hGH more strongly induced IGF-I gene expression than 22K-hGH. These results suggest that 20K and 22K hGH stimulate the IGF-I gene expression in the Ba/F3-hGHR through hGH receptors, and that the stronger effect of 20K hGH than that of 22K hGH in enhancing the IGF-I gene expression may be correlated with a 20K hGH specific receptor dimerization mechanism.

Cell Line↗

J-104129, a novel muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors.

A new class of 4-acetamidopiperidine derivatives has been synthesized and investigated for human muscarinic receptor subtype selectivity. Introduction of a hydrocarbon chain of appropriate length into the piperidine nitrogen of the racemic N-(piperidin-4-yl)-2-cyclobutyl-2-hydroxy-2-phenylacetamide platform conferred up to 70-fold selectivity for human muscarinic M3 receptors over M2 receptors. Subsequent synthetic derivatizations resulted in highly potent M3 receptor antagonists with selectivity greater than two orders of magnitude for M3 over M2 receptors, from which the analogue 4r was selected. Preparation of both enantiomers of 4r led to the identification of (2R)-N-[1-(4-methyl-3-pentenyl)piperidin-4-yl]-2-cyclopentyl-2-hyd roxy-2-phenylacetamide (J-104129, (R)-4r), which exhibited 120-fold selectivity for M3 receptors (Ki = 4.2 nM) over M2 receptors (Ki = 490 nM). In isolated rat trachea, (R)-4r potently and specifically antagonized acetylcholine (ACh)-induced responses with a K(B) value of 3.3 nM. The highly subtype-selective profile was also seen in isolated rat tissue assays (50-fold) and in anesthetized rats (> 250-fold). Oral administration of J-104129 ((R)-4r) antagonized ACh-induced bronchoconstriction with an ED50 value of 0.58 mg/kg in rats. Thus, J-104129 ((R)-4r) may effectively facilitate bronchodilation in the treatment of obstructive airway disease.

Alkenes↗

Lithium and clonazepam treatment of two cases with cluster headache.

Patients with cluster headache are often treated with lithium. However, there are some patients who can not be fully treated with lithium alone. Two patients with cluster headache were treated with clonazepam, one of the most potent benzodiazepines. Lithium prolonged the period of remission, and the addition of clonazepam further prolonged it in case 1. Treatment with clonazepam reduced the symptoms in case 2, and when combined with lithium, the disorder went into remission after 6 months. These findings suggest that the combination of lithium and clonazepam may be effective in patients with cluster headache.

Adult↗

Expression and purification of a mutant human growth hormone that is resistant to proteolytic cleavage by thrombin, plasmin and human plasma in vitro.

The region having a sequence from amino acid 134 to 150 in human growth hormone (hGH) is known to be cleaved by proteases in human plasma, plasmin and thrombin. In this study, oligonucleotide primer-directed mutagenesis was used to produce recombinant mutant hGHs resistant to limited proteolysis by these proteases. Substitution of Arg134 and Thr135 of hGH with Asp134 and Pro135 yielded a thrombin-resistant hGH mutant, and substitution of Arg134, Thr135 and Lys140 with Asp134, Pro135 and Ala140 yielded a plasmin-resistant hGH mutant. The latter mutant hGH was also insensitive to in vitro proteolysis by human plasma incubated for 7 days. These alterations in amino acid residues of hGH did not disrupt its biological conformation and retained full growth promoting activities on rat Nb2 cells and human T-47D breast cancer cells.

Animals↗

A case of Mucinous Carcinoma of the Male Breast with Unusual Ultrasonographic Findings Mimicking Phyllodes Tumor.

Mucinous carcinoma of the male breast is a rare histological type of cancer. We describe a 35-year-old male with mucinous carcinoma of the right breast. His breast mass enlarged subacutely, and became painful over a period of 2 months. Ultrasonography demonstrated echoes of a large multilocular cystic lesion with partially heterogenic internal echoes suggesting a phyllodes tumor. A modified radical mastectomy was performed, and histopathologic examination revealed mucin-producing solid or cribriform atypical cells with fibrous granulation tissue and hemosiderin deposition. The patient recovered uneventfully, and is still free of recurrence 30 months after his operation. The prognosis for male breast cancer can be improved by early diagnosis and appropriate multidisciplinary therapy.

Journal Article↗

X-ray absorption of bromonaphthalene dissolved in supercritical fluid xenon.

The results of Br K-edge X-ray absorption measurements of 1-bromonaphthalene dissolved in supercritical fluid Xe are reported. As the pressure of Xe confined in a high-pressure cell is increased, the absorption spectrum of bromonaphthalene gradually appears, showing that Xe in the supercritical fluid state solvates the bromonaphthalene molecule. The spectrum of the dissolved sample shows a remarkable difference from that of the pure liquid sample in the near-edge region of the X-ray absorption spectrum, reflecting the interaction of the solute material with solvent Xe. Ab initio full multiple-scattering calculations can reproduce the spectral features qualitatively. A large value of the Debye-Waller factor must be introduced to give the best fit, corresponding to a large degree of spatial disorder and violent thermal vibration of the Xe atoms around the Br atom.

Journal Article↗

X-ray absorption fine structure of V(2)O(5) and Li(x)V(2)O(5).

Vanadium K-edge XAFS measurements of five compounds were carried out. The compounds studied were crystalline V(2)O(5) and four types of Li(x)V(2)O(5) with different insertion levels x, which show different EMFs (2.0-3.4 V). The EXAFS data analysis shows no remarkable difference in the V-O distances in the five compounds, showing that the structure of the VO(5) square pyramids changes only slightly as lithium atoms are intercalated into the V(2)O(5). In the XANES spectra, three peaks are observed for crystalline V(2)O(5) and Li(x)V(2)O(5) (3.4 V). When the EMF is decreased, the intensity difference between the first and second peaks disappears and the third peak shifts to lower energy. The XANES data were analysed using full multiple-scattering calculations. In the calculated spectra the intensity of the first peak increases as the V(2)O(5) intercalates lithium atoms.

Journal Article↗

The effect of short-term continuous epidural morphine on postoperative pain after laparoscopic cholecystectomy.

This study was undertaken to determine whether short-term continuous epidural analgesia using morphine would relieve pain after laparoscopic cholecystectomy. The authors retrospectively reviewed the clinical data of 182 cases who had undergone a laparoscopic cholecystectomy. These cases were divided into four groups according to their anesthetic modes as follows: a control group with general anesthesia only (n = 37); group I, general anesthesia combined with one shot of epidural morphine (n = 78); and group II, general anesthesia combined with continuous epidural analgesia using morphine (IIa for 12 h (n = 33); IIb for 8 h (n = 34)). The pain score on a four-category verbal scale and the frequency of analgesic use were investigated. There were no differences in the background characteristics of the patients among the groups, except for the duration of surgery (I vs IIa; P = 0.006). The pain scores were significantly different between the control group and the other groups. The frequency of analgesic use in the control group was also significantly higher than in the other groups. A tendency toward a higher frequency of analgesic use in group I, compared with that in groups IIa and IIb, was observed. These findings thus suggest that short-term continuous epidural analgesia using morphine can effectively relieve postoperative pain after a laparoscopic cholecystectomy.

Analgesia, Epidural↗

Anomalous duplicated cystic duct as a surgical hazard: report of a case.

Anomalies of the biliary ductal system are not uncommon, and their clinical significance is variable. We present herein the case of a 70-year-old Japanese woman found to have an anomalous duplicated cystic duct, which is an extremely rare congenital anomaly. Intraoperative delineation of the anomaly by real-time cholangiograms assisted us in being able to subsequently perform a safe cholecystectomy. This case serves to demonstrate the importance of being aware of the possibility of potential biliary variations in order to avoid ductal injuries during biliary surgery.

Aged↗

Malignant thymoma with direct invasion into the peritoneal cavity: report of a case.

Extrathoracic invasions or metastases from thymomas are extremely rare. We describe herein the case of a patient with malignant thymoma which recurred three times during an 8-year period and invaded directly into the peritoneal cavity, involving the gastrointestinal tract. The huge thymoma was completely resected, along with the fornix of the stomach, the transverse colon, and the 8th, 9th, and 10th ribs. Careful observation and multidisciplinary treatment against recurrent thymoma will be requisite for this patient, even though the tumor has been completely resected.

Gastrointestinal Neoplasms↗

The 3-year course and outcome of patients with major depression and silent cerebral infarction.

We retrospectively investigated the relationship between major depression and silent cerebral infarction (SCI) over a 3-year period in 64 patients older than 50 years of age with unipolar depression. All patients underwent magnetic resonance imaging (MRI) at their first admission for depression and were classified into groups based on the presence or absence of SCI. The number of admissions due to depression was greater in the SCI (+) group (N = 32) than in the SCI (-) group (N = 32) (P < 0.05). The incidences of delirium and neurological disorders were significantly higher in the SCI (+) group than in the SCI (-) group. Our findings suggest that patients with depression and SCI had a higher rate of hospitalization and were more likely to develop psychiatric and neurological disorders than patients with depression without SCI.

Age of Onset↗