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Biomedical subjects

M Tanabe

Publications and source records attributed to M Tanabe.

At least 19 recordsLinked to original sources

Human bone marrow stromal cell lines from myeloma and rheumatoid arthritis that can support murine pre-B cell growth.

In order to elucidate the pathologic significance of the bone marrow (BM) microenvironment in multiple myeloma (MM) and rheumatoid arthritis (RA), we established patient- or healthy donor (HD)-derived BM stromal cell lines by transfecting the plasmid for expression of SV40 large T Ag and examined their ability to support the stromal cell-dependent growth of a pre-B cell line, DW34. The means of recovered cell numbers of DW34 co-cultured with MM- and RA-derived BM stromal cell lines ranged from 6- to 10-fold more than those with HD-derived ones. Their enhanced ability to support DW34 cell growth was not caused by cytokines, including IL-6, IL-7, and c-kit ligand, although exogenous IL-7 could augment the growth-supporting ability. DW34 cell growth on the stromal cell lines was abolished by inhibiting cell-to-cell interaction with a membrane filter. FACS analysis revealed that the stromal cell lines did not express LFA-1 alpha, beta, NCAM, or ELAM-1. Both patient and HD BM stromal cell lines variably expressed ICAM-1, VCAM-1, and CD44. However, surface expression levels of these molecules did not correlate with the ability of the stromal cell lines to support DW34 cell growth. Taken together, these results suggested that BM microenvironment might play important roles in the pathogenesis of MM and RA.

Animals

Beta-chain broadens range of CD8 recognition for MHC class I molecule.

It is known that the alpha-chain of CD8 binds to a negatively charged loop composed of residues 223 to 229 on MHC class I Ag and that binding of CD8 alpha enhances Ag recognition of T cells. We have recently shown that the mouse CD8 alpha homodimer does not bind to either the HLA class I alpha 3 domain or a mutant of H-2Kb Ag containing a substitution of glutamine for methionine at residue 224, which brings this residue toward the human consensus. Here we report a complementary study of the CD8 beta-chain. The functional role of the CD8 beta-chain was analyzed by using four T cell hybridoma lines expressing mouse CD8 alpha and transfected with the mouse CD8 beta gene. As compared with the lines expressing only CD8 alpha, allorecognition of the chimeric H-2Kb Ag that contains the HLA class I alpha 3 domain was enhanced in lines expressing both CD8 alpha and -beta. This enhancement was blocked by either anti-CD8 mAb or anti-HLA class I alpha 3 domain mAb. In addition, we show that CD8 alpha beta binds the H-2Kb mutant Ag at residue 224. These results suggest that the beta-chain allows the CD8 alpha beta heterodimer to recognize the chimeric H-2Kb Ag. A model for the role of the beta-chain is presented.

Animals

Structural and functional analysis of monomorphic determinants recognized by monoclonal antibodies reacting with the HLA class I alpha 3 domain.

To identify mAb reacting with the HLA class I alpha 3 domain, 14 mAb recognizing monomorphic determinants expressed on HLA-A, B, and C Ag or restricted to HLA-B Ag were screened in indirect immunofluorescence with mouse L cells expressing HLA-B7/H-2Kb chimeric Ag. mAb CR1S63, CR10-215, CR11-115, and W6/32 were found to react with the HLA class I alpha 3 domain in addition to the alpha 2 domain. mAb Q1/28 and TP25.99 were found to react only with the HLA class I alpha 3 domain. The determinants recognized by the six mAb were mapped on the HLA class I alpha 3 domain by indirect immunofluorescence staining of L cells expressing H-2Kb Ag containing different segments of the HLA-B7 alpha 3 domain chimerized with the H-2Kb alpha 3 domain. mAb TP25.99 reacts with chimeric Ag containing the HLA-B7 184 to 199 stretch, mAb CR10-215 and CR11-115 react with chimeric Ag containing the HLA-B7 184 to 246 stretch, mAb CR1S63 and Q1/28 react with chimeric Ag containing the HLA-B7 184 to 256 stretch, and mAb W6/32 reacts with chimeric Ag containing the whole HLA-B7 alpha 3 domain. Functional analysis using human CD8 alpha-bearing mouse H-2Kb-specific T cell hybridoma cells (HTB-Leu2) showed that only mAb TP25.99 inhibited IL-2 production by HTB-Leu2 cells stimulated with L cells expressing KbKbB7 Ag. This inhibition may occur because of the spatial proximity of the determinant defined by mAb TP25.99 to the CD8 alpha binding loop and/or because of change(s) in the conformation of the CD8 alpha binding loop induced by the binding of mAb TP25.99 to the HLA class I molecule. Furthermore, mAb TP25.99 inhibited the cytotoxicity of CD8-dependent and CD8-independent CTL clones. These results indicate that mAb TP25.99 has unique specificity and functional characteristics. Therefore it represents a valuable probe to characterize the role of the HLA class I alpha 3 domain in immunologic phenomena.

Amino Acid Sequence

Enzymatic properties of the phosphorylated urokinase-type plasminogen activator isolated from a human carcinomatous cell line.

Enzymatic properties of phosphorylated urokinase plasminogen activator (P-uPA) (1) extracted from human carcinomatous cell line Detroit 562 cells were compared with those of non-phosphorylated uPA of urinary origin (nP-uPA). Using plasminogen as a substrate, the Km and Kcat of P-uPA were higher than that of nP-uPA while the Kcat/Km was lower. By zymography, a greater degree of plasminogen activation was observed. Concanavalin A reacted to both the enzymes. P-uPA had a low affinity for the inhibitors of plasminogen activator PAI-1 and PAI-2, and was inhibited only by the excess amounts of inhibitors. For PAI-1, and the KIs of P-uPA was greater and for PAI-2, KI was higher for P-uPA. These alterations by phosphorylation enable uPA to be more efficient in a focal proteolysis through plasminogen activation.

Amino Acid Sequence

Effectiveness of planar image and single photon emission tomography of thallium-201 compared with gallium-67 in patients with primary lung cancer.

A comparative study of planar images and single photon emission tomography (SPET) of thallium-201 chloride and gallium-67 citrate was performed in 38 patients with proven primary lung cancer to detect the primary lung tumour and to establish the presence of metastasis in the lung hilum and mediastinum. The findings of planar images and SPET were compared with the pathological findings after thoracotomy. It was shown that 201Tl studies were superior to 67Ga studies for evaluation of the primary lesion and lymph node metastases.

Aged

Blood flow through the ophthalmic veins during exercise in humans.

The blood from the face flows into the intracranium through the ophthalmic veins when human subjects become hyperthermic. To investigate a possible mechanism underlying this change in direction of flow, five young men were subjected to either passive body warming or exercise on a cycle ergometer, in a climatic chamber whose air temperature and relative humidity were 28 degrees C and 40%. Tympanic (Tty) and oesophageal temperatures, forehead sweat rate (msw), skin blood flow (Qsk) and blood flow through the ophthalmic vein (Qov) were measured, and the mean skin (Tsk) and mean body (Tb) temperatures were computed. Passive body warming was induced by a box-shaped body warming unit enclosing all but the subject's head. Exercise was performed either at an intensity of 60% maximal oxygen consumption or with the intensity increasing in increments. During both tests, msw and Qsk started to increase shortly after the imposition of the heat load. The Qov began to change with the venous blood flowing from the face into the intracranium and a complete reversal in the direction of Qov (from the face to the intracranium) came significantly later than the increases in msw and Qsk. The Tty at the time of flow reversal was the same in both tests. The Tsk (and hence Tb) at flow reversal was, however, significantly higher during passive body warming than during exercise. The mechanism for switching the direction of Qov appeared to have been triggered by a high temperature in the brain, and not by thermal input from the periphery of the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant.

The pharmacological properties of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized, centrally acting muscle relaxant, were studied in rats. The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation. The compound, however, showed no effect on the basal discharge of Ia afferent fibers. The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time. In rats anesthetized with halothane, CS-722 did not affect the electroencephalogram (EEG) arousal response, which was elicited by stimulation of the reticular formation. The results of this study suggest that CS-722 can exert a muscle relaxant action, at a dose range at which depression of the ascending reticular activating system was negligible. The results also suggest that depressions of the gamma-motor system and the polysynaptic reflex may contribute to the muscle relaxant action of CS-722.

Animals

Mechanisms of spinal reflex depressant effects of CS-722, a newly synthesized centrally acting muscle relaxant, in spinal rats.

The mechanisms of the depressant action of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized centrally acting muscle relaxant, on spinal reflexes were investigated in spinal rats. The drug CS-722 (50 mg/kg, i.v.) depressed the polysynaptic reflex but was less effective on the monosynaptic reflex. Eperisone-HCl (10 mg/kg, i.v.) and baclofen (2 mg/kg, i.v.) markedly decreased the monosynaptic and polysynaptic reflexes, with longer durations than CS-722; CS-722, eperisone and baclofen depressed the dorsal root reflex. The excitability of the motoneurone was reduced by CS-722 and eperisone. Excitability of the primary afferent fibres was reduced by CS-722, while eperisone and baclofen had no effect. Both CS-722 and eperisone did not have a depressant influence on the focal synaptic potential. These results suggest that CS-722 and eperisone but not baclofen, have a common motoneurone-membrane-stabilizing action and that this action may contribute, in part, to the spinal reflex depressant effects of CS-722 and eperisone.

Animals

Primary retroperitoneal plasmacytoma with tumor thrombus within the renal vein.

A case of primary retroperitoneal plasmacytoma causing a tumor thrombus within the renal vein is described. The use of radiographic techniques, including ultrasonography, computerized tomography and angiography, facilitated an accurate diagnosis. Tumor thrombi within the renal vein are rare except in cases of primary renal or adrenal neoplasms. In a patient with radiological evidence of retroperitoneal tumor and tumor thrombus within the renal vein plasmacytoma should be considered in the differential diagnosis of retroperitoneal neoplasms.

Aged

Antigen recognition by the T cell receptor is enhanced by CD8 alpha-chain binding to the alpha 3 domain of MHC class I molecules, not by signaling via the cytoplasmic domain of CD8 alpha.

The binding specificities and function of mouse CD8 were studied using a CD4-CD8- allospecific T cell hybridoma, chimeric class I MHC molecules, and a CD8 alpha deletion mutant. By transfecting the mouse CD8 alpha gene into a IL-2 producing, H-2Kb specific hybridoma, IL-2 production was increased when L cells expressing Kb were used as stimulators. However, no increase in IL-2 was observed when a KbKbB7 hybrid molecule, composed of the alpha 1 and alpha 2 domains of H-2Kb, and the alpha 3 domain of HLA-B7, was used as a stimulator. Comparison between T cell hybridomas that expressed full-length CD8 alpha and a deletion mutant lacking part of the cytoplasmic domain revealed identical responsiveness for H-2Kb. The data suggest that the mouse CD8 alpha homodimer does not bind to the alpha 3 domain of HLA class I molecules and that CD8 alpha acts as a co-receptor with the TCR by binding the same MHC molecule for alloantigen recognition. Our data also provide evidence that CD8 alpha signal transduction through its cytoplasmic tail by association with p56lck is not an absolute requirement for antigen recognition by T cells.

Animals

[A case of intracranial multiple nonspecific granulomas related to rheumatic disease: with special reference to magnetic resonance imaging].

We encountered a rare case of a 48-year-old man with intracranial multiple granulomas secondarily caused by rheumatic disease. This was proven surgically after an 11-year course of remissions and deteriorations. In 1980, at the age of 32 years, the patient was first seen at the clinic of Neurology of the University Hospital, complaining of swelling and arthralgia of the joints of the knee, ankle, and wrist and with remittent fever and visual disturbance. The patient was diagnosed as having possible rheumatoid arthritis, and treated with administration of 30mg/day of prednisolone, which greatly improved the symptoms. The administration of 5 to 10mg/day of prednisolone had been continued after discharge from hospital. In 1985, visual acuity of the left eye decreased, and left facial hypesthesia developed. The patient was rehospitalized at the same clinic, and treated with 100mg/day of prednisolone, which again diminished the symptoms. Computed tomography(CT) on admission showed a high density mass with contrast enhancement in the left cavernous region. In addition to the left cavernous mass, a high density mass was detected by CT in the left parietal lobe, in 1987. Visual acuity of the left eye deteriorated in 1989. Because his response to prednisolone had decreased, the visual symptom was treated with gold sodium, which acted effectiveness. Symptoms deteriorated again in 1990. Early in 1991, CT and magnetic resonance imaging showed a new mass at the right frontal lobe, while the mass in the left cavernous region had increased in size. The patient was transferred to the clinic of Neurosurgery for surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Efficacy of magnetic resonance imaging in treatment of neuroblastoma].

Magnetic resonance imaging (MRI) was performed in 36 children with neuroblastoma at Chiba University from 1984 through 1989, and 29 patients of them were discussed about efficacy of MRI in treatment of neuroblastoma in this paper and the results were as follows. 1) MRI was difficult to differentiate tumor from normal kidney in the image intensity and was more efficient in determining the relationship of tumor to liver and to vascular structures. 2) MRI was better than CT in detecting the size and extent of tumor mass and in identifying lymph node spread using multiple planes. 3) MRI was more efficient than CT in defining displacement and encasement of renal vessels by tumor. It was useful to predict to reserve kidney before surgery. 4) MRI was useful to monitor tumor response to combined modalities of therapy. A favorable response was seen as a change in the image intensity in bone marrow metastases of neuroblastoma.

Adrenal Gland Neoplasms

Expression of N-myc and c-src protooncogenes correlating to the undifferentiated phenotype and prognosis of primary neuroblastomas.

Genomic amplification of the N-myc protooncogene in neuroblastomas correctly predicts poor outcome for the patients. However, the prognosis for neuroblastomas with a single copy of N-myc is also poor in cases diagnosed after 1 year of age but good in infantile cases. To elucidate the different prognoses depending upon the age of the patients with neuroblastoma, we performed an analysis of the expression of protooncogenes related to neural differentiation. We examined the genomic amplification of N-myc in 26 specimens of neuroblastomas and further analyzed 22 of the 26 cases for expression of N-myc, c-src, c-Ha-ras, and c-fos. Consequently, we observed frequent overexpression of N-myc in undifferentiated neuroblastomas and enhanced expression of c-src and c-Ha-ras in infantile neuroblastomas with favorable prognosis and in neuroblastomas differentiated by chemotherapy. These findings suggest that c-src and c-Ha-ras play important roles in the neural differentiation of infantile neuroblastomas.

Blotting, Northern

Enhancement of finger blood flow response of postprandial human subjects to the increase in body temperature during exercise.

The present study was performed to investigate the effect of food intake on thermoregulatory vasodilatation in seven healthy male volunteers. The changes in oesophageal (Toes) and mean skin temperatures, finger and forearm blood flows (BF), oxygen consumption (VO2) and heart rate (fc) with and without food intake were measured before and during a 40-min exercise at an intensity of 35% maximal O2 consumption at an ambient temperature of 25 degrees C. Exercise commenced 60 min after food intake. Ingestion of food equivalent to 50.2 kJ.kg body mass-1 elevated mean body temperature, BF, VO2 and fc in 60 min. Four subjects responded to exercise with a marked increase in finger BF and with no sweating (non-sweating group), while the other three responded with perspiration over almost the whole skin area and with little change in finger BF. Further analyses were made mainly in the non-sweating group. The postprandial increases in Toes, BF, VO2 and fc were persistent during exercise. The rate of increase in finger BF with the increase in Toes and mean body temperature was significantly greater with food intake than without. However, there was no difference in the response of forearm BF to exercise between the two conditions. These results suggested that food intake enhanced finger BF response to the increase in deep body temperature during exercise. It was also concluded that there was a regional difference in cutaneous vasomotor response to thermal load in the postprandial subjects.

Adult

Pancreatic cavernous hemangioma: CT, MRI, US, and angiography characteristics.

A large pancreatic cavernous hemangioma was found in a 30-year-old man with abdominal distention. Plain and contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US), and angiography were performed prior to operation. Contrast-enhanced CT and angiography showed a large poorly enhanced hypovascular tumor at the head of the pancreas. But MRI and US disclosed findings compatible with a cavernous hemangioma.

Adult

Schistosoma mansoni: higher free proline levels in the livers of infected mice.

The concentration of L-hydroxyproline in the liver of ICR female mice increased rapidly during the 8th to 11th weeks of Schistosoma mansoni infection. Free L-proline concentration began to increase about the 7th week and reached its maximum at the 8th to 9th weeks of the infection, when the granulomatous response to the schistosome eggs in the liver was most prominent, as indicated by the increase in liver wet weight and its deoxyribonucleic acid concentration. A significant increment in the total activity of ornithine-delta-transaminase (EC 2.6.1.13) and the decrease in the specific activity of proline oxidase (EC 1.4.3.2) became detectable in the liver homogenate of infected mice on the 8th week. However, changes in these enzymatic activities were not parallel to that of the hepatic free L-proline content. Intraperitoneal administration of S. mansoni egg granulomas or 15,000g x 30 min supernatant fluid of their extracts into uninfected, normal mice significantly increased the hepatic free L-proline content without any appreciable effect on the enzymatic activities of proline oxidase and ornithine-delta-transaminase. These findings suggest that S. mansoni egg granulomas contain a factor(s) which may be responsible for the elevation of free L-proline content in the fibrotic liver caused by experimental schistosomiasis mansoni.

Animals

Spontaneous thrombosis of an aneurysm of the middle cerebral artery with subarachnoid haemorrhage in a 6-year-old child: case report.

A 6-year-old boy had a sudden onset of rupture of an aneurysm of the middle cerebral artery. Narrowing of an artery proximal to the aneurysm was shown on an angiogram taken two days after the rupture. At operation, clipping of the aneurysm prevented further bleeding. This artery thrombosed spontaneously in the postoperative period. The outcome was favourable, and the patient returned to school life. Spontaneous thrombosis of an artery after subarachnoid haemorrhage in children is rare, and thrombosis of aneurysm is very rare. To our knowledge, this is the third reported case of spontaneous thrombosis of a cerebral saccular aneurysm with subarachnoid haemorrhage.

Cerebral Angiography