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T Arita

Publications and source records attributed to T Arita.

At least 37 records · Page 2Linked to original sources

Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth.

We previously reported a new type of signal-transducing adaptor molecule, STAM, which was shown to be involved in cytokine-mediated intracellular signal transduction. In this study, we molecularly cloned a 110-kDa phosphotyrosine protein inducible by stimulation with interleukin 2 (IL-2). The 110-kDa molecule was found to be a human counterpart of mouse Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) and to be associated with STAM. Tyrosine phosphorylation of Hrs is induced rapidly after stimulation with IL-2 and granulocyte-macrophage colony-stimulating factor as well as hepatocyte growth factor. The mutual association sites of Hrs and STAM include highly conserved coiled-coil sequences, suggesting that their association is mediated by the coiled-coil structures. Exogenous introduction of the wild-type Hrs significantly suppressed DNA synthesis upon stimulation with IL-2 and granulocyte-macrophage colony-stimulating factor, while the Hrs mutant deleted of the STAM-binding site lost such suppressive ability. These results suggest that Hrs counteracts the STAM function which is critical for cell growth signaling mediated by the cytokines.

Adaptor Proteins, Signal Transducing↗

STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction.

We previously identified a putative signal transducing adaptor molecule, named STAM, that contains an Src homology 3 (SH3) domain and immunoreceptor tyrosine-based activation motif (ITAM). In this report, we demonstrate the functional significance of STAM in cytokine-mediated signal transduction. STAM is associated with Jak3 and Jak2 tyrosine kinases via its ITAM region and phosphorylated by Jak3 and Jak2 upon stimulation with IL-2 and GM-CSF, respectively. An SH3 deletion mutant of STAM confers a dominant-negative effect on DNA synthesis mediated by IL-2 and GM-CSF. Furthermore, the wild-type STAM, but not STAM mutants deleted of SH3 and ITAM, significantly enhances c-myc induction mediated by IL-2 and GM-CSF. These results strongly implicate STAM in the signaling pathways for cell growth and c-myc induction immediately downstream of the Jaks associated with the cytokine receptors.

Adaptor Proteins, Signal Transducing↗

Abdominal aortic aneurysm: rupture associated with the high-attenuating crescent sign.

PURPOSE: To determine the histopathologic features of the ruptured abdominal aortic aneurysm associated with the high-attenuating crescent sign on computed tomographic (CT) scans and to suggest a possible mechanism for the rupture. MATERIALS AND METHODS: Histopathologic examination was performed with specimens from six patients with a ruptured aneurysm associated with the high-attenuating crescent sign and from eight patients with a nonruptured aneurysm and in whom the high-attenuating crescent sign was not present. RESULTS: Acute hemorrhage in the mural thrombus or aneurysmal wall coincident with the high-attenuating crescent sign was present in all six patients with a ruptured aneurysm. Clefts with seeping blood in the mural thrombus were seen in four patients with a ruptured aneurysm; intact specimens of the mural thrombus were not obtained in two patients because the hemorrhagic thrombus was fragile. Clefts with seeping blood were scattered from the inner to the outer layers of the mural thrombus. In the eight patients with uncomplicated aneurysm, no hemorrhage in the mural thrombus or aneurysmal wall was noted, and no clefts were seen. CONCLUSION: The cause of high-attenuating crescents in a ruptured aneurysm may be attributed to hemorrhage in the mural thrombus or in the aneurysmal wall.

Adult↗

Cloning of a novel signal-transducing adaptor molecule containing an SH3 domain and ITAM.

We molecularly cloned a cDNA coding for a novel phosphotyrosine molecule with a 70 kDa molecular mass, named STAM (signal transducing adaptor molecule), which is tyrosine-phosphorylated rapidly after stimulation with various cytokines such as IL-2, IL-3, IL-4, IL-7, GM-CSF, EGF and PDGF. STAM contains an SH3 (Src-homology 3) domain and the ITAM (immunoreceptor tyrosine-based activation motif), suggesting that STAM acts as an adaptor molecule involved in signal transducing pathways from the cytokine receptors.

Adaptor Proteins, Signal Transducing↗

Two-domain haemoglobin of the blood clam Barbatia lima resulted from the recent gene duplication of the single-domain delta chain.

The blood clam Barbatia lima subsp. from Amami-Oshima, Japan, expresses three types of haemoglobins in erythrocytes: a tetramer (alpha 2 beta 2), a homodimer (delta 2) and a polymer consisting of two kinds of chains, a 34 kDa two-domain (2D) globin and a delta chain. This is in sharp contrast to the congeneric clams B. reeveana (a North American species) and B. lima from Kochi, Japan, each containing a tetramer and a polymer consisting of the 2D globin, but not the delta chain. We have determined the cDNA-derived amino acid sequences of all four chains, alpha (163 residues), beta (155 residues), delta (152 residues) and 2D (308 residues) of B. lima (Amami-Oshima). The alpha chain has an extremely long N-terminal extension of 20 residues that may form a 'pre-A helix', and this makes the alpha chain the longest known globin. B. lima alpha and beta chains show about 50% sequence identity with the alpha and beta chains, respectively, of tetrameric haemoglobin from a related clam, Anadara trapezia. The B. lima homodimeric delta chain shows 71-74% identity with each of the two domains of the 2D chain, but only 39% identity with the homodimeric gamma chain of Anadara. In addition, the alignment of amino acid sequences of the delta chain and the two domains of the 2D chain revealed that the delta chain lacks one amino acid (Lys) at the C-terminus, suggesting that the C-terminal Lys (codon AAA or AAG) of the two domains of 2D chain could result from the stop codon TAA in the delta chain by nucleotide substitutions. These results, together with the fact that the delta and 2D chains form a polymeric haemoglobin, indicates that the delta chain is the ancestral single-domain globin for the 2D globin. The delta chain is expressed only in B. lima (Amami-Oshima), and appears to be a relic of molecular evolution.

Amino Acid Sequence↗

Is it possible to differentiate malignant mediastinal nodes from benign nodes by size? Reevaluation by CT, transesophageal echocardiography, and nodal specimen.

STUDY OBJECTIVE: To reevaluate whether it is possible to reliably differentiate malignant mediastinal lymph nodes from benign nodes by size, and to determine the frequency of metastases to normal-sized mediastinal lymph nodes that directly affects the sensitivity for detecting malignant mediastinal lymph nodes (N2 nodes) on CT. DESIGN: Prospective study of patients with non-small cell lung cancer. SETTING: Department of Radiology and First Department of Surgery, Yamaguchi University School of Medicine. PATIENTS: We examined 40 patients with non-small cell lung cancer, who underwent thoracotomy because of operable stage (stage I, II, IIIA) in preoperative staging, using CT and transesophageal echocardiography (TEE). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Lymph nodes 10 mm or greater in short-axis diameter on CT and TEE were considered abnormal. Furthermore, lymph node size was measured by TEE and nodal specimens in long- and short-axis diameter in each patient. Two hundred eight mediastinal lymph nodes were dissected and N2 nodes were present in 28% of patients (11/40); in 7 of these 11 patients (64%), mediastinal lymph node metastases were misdiagnosed on CT because of normal-sized N2 nodes. Furthermore, in 73% of N2 nodes, nodal size was normal on TEE. There were no significant difference in both diameters between malignant mediastinal lymph nodes and benign nodes on TEE and nodal specimens. CONCLUSIONS: It is not possible to reliably differentiate malignant mediastinal nodes from benign nodes by size alone, and we should be aware of high frequency of normal-sized N2 nodes in patients with operable stage of lung cancer.

Adult↗

[Analysis of proximal conduction time of the median nerve in patients with diabetes mellitus].

Proximal conduction time (PCT) of the median nerve was calculated from the data obtained by conventional motor conduction studies in 272 diabetics and in 35 age-matched healthy controls. M-latency and F-latency obtained by stimulation at the wrist (Mw and Fw, respectively) and M-latency at the Erb's point (Me) were used to calculate PCT (Fw + Mw - 2Me), which represents turnaround time between Erb's point and anterior horn cell. Each indices were corrected using the standard patient's height of 160cm. Severity of diabetic neuropathy was shown by the polyneuropathy index (PNI), which was calculated from 12 indices derived from the motor nerve conduction studies on 4 nerves of the right arm and leg. Significant differences were found in Mw, Fw and Me between diabetics and controls (p < 0.01), although the results of PCT were similar between them. In diabetics Mw (r = -0.55), Fw (r = -0.56) and Me (r = -0.60) had a significant negative correlation with PNI, but the correlation between PCT and PNI was relatively low (r = -0.22). Using the proximal conduction time calculated readily from conventional motor nerve conduction studies, delay in the proximal conduction was shown to be smaller than that in the distal conduction in diabetic polyneuropathy.

Diabetic Neuropathies↗

Two-domain hemoglobin from the blood clam, Barbatia lima. The cDNA-derived amino acid sequence.

The blood clam, Barbatia lima, from Kochi, Japan, expresses a tetrameric (alpha 2 beta 2) and a polymeric hemoglobin in erythrocytes. The latter hemoglobin is composed of unusual 34-kDa hemoglobin with a two-domain structure, and its molecular mass (about 430 kDa) is exceptionally large for an intracellular hemoglobin. The 3' and 5' parts of the cDNA of B. lima two-domain globin have been amplified separately by polymerase chain reaction and the complete nucleotide sequence of 1147 bp was determined. The open reading frame is 930 nucleotides in length and encodes a protein with 309 amino acid residues, of which 73 amino acids were identified directly by protein sequencing. The mature protein begins with the acetylated Ser, and thus the N-terminus Met is cleaved. The molecular mass for the protein was calculated to the 35,244 Da. The cDNA-derived amino acid sequence of B. lima two-domain globin shows 89% homology with that of two-domain globin from B. reeveana, a North American species. The sequence homology between the two domains is 75%, suggesting that the two-domain globin resulted from the gene duplication of an ancestral 17-kDa globin.

Amino Acid Sequence↗

Bronchogenic carcinoma: incidence of metastases to normal sized lymph nodes.

BACKGROUND: The incidence of metastases to mediastinal lymph nodes was evaluated in patients with normal sized mediastinal nodes on the computed tomographic (CT) scan who underwent thoracotomy. The use of hilar lymph nodes in predicting mediastinal lymph node metastases was also assessed. METHODS: Ninety patients with non-small cell lung cancer who later underwent thoracotomy wer prospectively examined by CT scanning. Lymph nodes with a short axis diameter of 10 mm or more were considered abnormal. RESULTS: Mediastinal lymph node metastases were present at thoracotomy in 19 patients (21%). In 14 these lymph node metastases were misdiagnosed because the nodes were normal in size on the CT scan. In only one of the 19 patients with N2 nodes was an N1 lymph node enlarged, and four of the 19 patients with N2 nodes had metastases to these mediastinal nodes without N1 disease ("skipping metastases"). CONCLUSIONS: Metastases in normal sized nodes seen on the CT scan are a major problem in staging. Hilar lymph nodes did not help to predict reliably the presence or absence of metastases to the mediastinal lymph nodes.

Adenocarcinoma↗

The cDNA-derived amino acid sequence of chain II of the heterodimeric hemoglobin from the blood clam Barbatia virescens.

The blood clam Barbatia virescens expresses a unique heterodimeric hemoglobin consisting of chains I and II in erythrocytes. This is in sharp contrast to the tetrameric (alpha 2 beta 2) and polymeric two-domain hemoglobins of the congeneric species Barbatia reeveana and Barbatia lima. The 3' and 5' parts of the cDNA of B. virescens chain II have been amplified separately by polymerase chain reaction (PCR), and the complete nucleotide sequence of 690 bp was determined. The open reading frame is 477 nucleotides in length and encodes a protein with 158 amino acid residues, of which 120 amino acids were identified directly by the protein sequencing of the peptides obtained from digestions with trypsin, S. aureus V8 protease and pepsin. The mature protein begins with the blocked Ser, and thus the N-terminal Met is cleaved away. The molecular mass for the protein was calculated to be 17605 Da. The cDNA-derived amino acid sequence of B. virescens heterodimeric chain II shows the highest homology (42%) with that of B. virescens chain I, but shows lower homology (32-35%) with those of tetrameric alpha and beta chains of B. lima. This indicates that B. virescens chains I and II do not correspond to B. lima alpha and beta chains, namely the heterodimeric hemoglobin is a unique gene product expressed only in B. virescens.

Amino Acid Sequence↗

[Effect of diabetic control on the progression of neuropathy].

We investigated the relationship between blood levels of HbA1, an indicator of diabetic control, and the polyneuropathy index (PNI), an indicator of diabetic polyneuropathy. A total of 175 patients with non-insulin-dependent diabetes mellitus were followed for more than 3 years and were subjected to a series of motor conduction studies every 1 to 3 years. The PNI was calculated as a mean percentage of normal values for 12 indices derived from the conduction velocity and long-distance latency in motor conduction studies of 4 nerves. The mean follow-up period was 5.0 years, and during that time the mean decrease in the PNI was 2.7%. There was a significant negative correlation between mean HbA1 levels (X) and the percent changes in PNI per year (Y), and the equation for the regression line was Y = -0.102X + 0.37 (r = 0.283, p < 0.001). The higher the HbA1 level during this period, the larger the decline in PNI was. In patients with low initial PNI levels the change in PNI tended to be small in spite of high HbA1 levels. Likewise, in patients with high initial PNI levels the decrease in PNI tended to be large despite relatively good control of their HbA1 levels. However, since there were many patients whose HbA1 levels were not correlated with the reduction in PNI, there may be some unknown factors, possibly genetic, that play a role in the progression of polyneuropathy in diabetic patients.

Diabetes Mellitus, Type 2↗

[Penetrating head injury caused by weed--case report].

A case of penetrating head injury caused by weed was reported. A 69-year-old man fell from a bicycle and was stuck by the hard stalk of weed through the right nasal cavity. On admission the patient was fully alert and with no neurological deficits. The weed was pulled out at an out-patient department and then he became semicomatose and hemiplegic on the left side together with an occurrence of nasal bleeding. Subsequent computed tomographic (CT) scan showed an intracerebral hematoma in the right frontal lobe. The hematoma was immediately evacuated and the dural defect, lateral to the cribriform plate, was closed. It is stressed that neuroradiological evaluation with CT scan and/or magnetic resonance imaging (MRI) is mandatory because an information about an anatomical location of penetrating objects and intracranial complications are essential to a decision-making of surgical strategy. The objects should be urgently removed in a surgical exposure of the intracranial lesion and the contused brain should be debrided with a repair of the lacerated dura mater.

Aged↗

[High-resolution MR imaging of the mediastinum and hilus of the lung using surface-coils].

High-resolution MR imaging using surface-coils (Helmholtz-coil) was performed on patients with hilar lung cancer and healthy volunteers. We evaluated the clinical usefulness of this technique compared with MR imaging performed with a conventional body-coil. Although the signal-to-noise ratio was slightly decreased, normal anatomic structures, hilar masses, and enlarged lymph nodes were distinctly visualized in comparison with those on MR images obtained with a body-coil. High-resolution MR imaging with the Helmholtz-coil seemed to be useful for the evaluation of mediastinal and hilar disease, and may able to supplant MR imaging with a conventional body-coil in routine examinations.

Humans↗

[Blood flow pattern in pulmonary atelectasis with color Doppler flow imaging].

Blood flow pattern in the lesion was evaluated in 4 patients with pulmonary atelectasis by color Doppler flow imaging synchronized electrocardiography. The pulsatile signal and triphasic signal were detected, whereas the continuous signal was not. It seemed that in pulmonary atelectasis the pulsatile signal was the blood flow signal in the pulmonary artery and the triphasic signal was the blood flow signal in the pulmonary vein.

Aged↗

[Effect of hyperthermia on blood flow in VX2 tumor transplanted in rabbit: evaluation with color Doppler flow imaging and dynamic MR imaging].

Effect of hyperthermia on blood flow was evaluated using VX2 rabbit carcinoma in both legs. Microwave energy at 2450 MHz was used to heat tumors for 40 minutes. An outer cannula of 18 G Erasta was implanted in the depth of 2 cm in tumor to measure the temperature and to maintain at 43.0 degrees C-44.0 degrees C. The blood flow in tumors was evaluated by color doppler flow imaging and dynamic MRI. Disturbance of blood flow in the depth of surface 0 cm to 2 cm in tumors was showed at 10 minutes starting 43.0 degrees C heating and at almost all sites disappearance of blood flow was showed at 40 minutes using color doppler flow imaging. But the blood flow beyond the depth of 2 cm was not so disturbed at 40 minutes, relatively. After hyperthermia T 1 WI and T 2 WI in heated tumor were no difference comparing with those in control tumor, but heated tumor showed no enhancement using dynamic MRI with TURBO-FLASH technique and post-enhanced T1 WI. Histologically, there was extensive tumor necrosis and thrombus formation in heated tumor after 3 days and 1 week. Therefore color doppler flow imaging and dynamic MRI were considered to be useful for evaluation of blood flow in tumor after and during hyperthermia.

Animals↗

Enantioselective pharmacokinetics of homochlorcyclizine: disposition of (+)- and (-)-homochlorcyclizine after intravenous and oral administration of racemic homochlorcyclizine to rats.

Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg-1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg-1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (-)-isomer. The AUC0-infinity values of the (+)- and (-)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (-)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments.

Administration, Oral↗

Effect of first-pass metabolism on enantioselective pharmacokinetics after oral administration of (+)-, (-)- and racemic homochlorcyclizine to rats.

The enantioselective relationship between the pharmacokinetics and hepatic metabolism of homochlorcyclizine hydrochloride (HCZ) was investigated using rats. There were no significant differences in blood concentrations between the three forms after intravenous administration (5 mg/kg) of (+)-, (-)- and racemic HCZ. On the other hand, there were significant differences in the pharmacokinetics between (-)- and (+)-HCZ and between (-)- and racemic HCZ after oral administration (50 mg/kg) of these three forms. The Cmax and AUC0-infinity of (-)-HCZ were lower than those of (+)-isomer and racemate, and its CLo was clearly higher than the others. The (+)-isomer and racemate showed no significant differences in their pharmacokinetic parameters. At a lower dose (10 mg/kg), however, no enantiomeric differences were found in the pharmacokinetic parameters of (+)- and (-)-HCZ. Also examined was the cytochrome p-450-dependent-oxidative metabolism of (+)-, (-)- and racemic HCZ in vitro using rat liver 9000 x g supernatant fraction. The in vitro metabolism of (-)-HCZ was extremely fast, compared with those of the (+)-isomer and the racemate. The Vmax in vitro showed a good correlation with the CLo in vivo after oral administration (50 mg/kg) of all three forms of HCZ. In vitro study of enantiomeric inhibition of the metabolism showed that (+)-HCZ was a competitive inhibitor of (-)-HCZ metabolism, with a Ki of 6.96 microM. (-)-HCZ was also a competitive inhibitor of (+)-HCZ metabolism, with a Ki of 20.4 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗