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Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 865 records · Page 48Linked to original sources

Mapping of transcriptional regulatory domains of pseudorabies virus immediate-early protein.

The 180 kilodalton immediate-early protein (IE180) of pseudorabies virus functions as a strong transactivator of several different promoters and also as a repressor of its own transcription. To map the functional domains of IE180, we prepared various truncated mutants and analyzed their transcriptional regulatory activities using the chloramphenicol acetyl transferase (CAT) assay. Analysis of mutants truncated from the carboxy-terminal end of the 1,460-amino acid polypeptide showed that a polypeptide possessing amino acids 1 to 1,081 retained significant functions of transactivation and autoregulation potential. On the other hand, removing amino acids 1 to 131 resulted in a complete loss of transactivation potential, indicating that the domain responsible for transactivation is located in the amino-terminal end of IE180. Additional amino-terminal truncation up to amino acid 453 did not affect the autoregulation activity, indicating that the region between amino acids 454 and 1081 has autoregulation potential.

Amino Acid Sequence↗

Primary malignant fibrous histiocytoma of the diaphragm: report of a case.

We present herein the case of a 55-year-old man with primary malignant fibrous histiocytoma (MFH) of the diaphragm. He was admitted to our hospital with right anterior chest pain, where diagnostic imaging showed a huge tumor in the right diaphragm with a tumor thrombus in the vena cava, spreading to the left lobe of the liver and the pericardium. Although invasion into the right lung was identified at the time of surgery, the entire tumor was removed. Histopathological examination of the resected specimen revealed the characteristics of MFH. We discuss the clinical features of this patient in comparison with the few previous reports on MFH of the diaphragm.

Diagnostic Imaging↗

Contemporaneous bilateral postero-ventral pallidotomy for early onset "juvenile type" Parkinson's disease. Case report.

Early onset "juvenile type" Parkinson's disease is commonly associated with disabling bilateral levodopa-induced dyskinesias. We report here a successful contemporaneous bilateral postero-ventral pallidotomy performed on a 46-year-old male with juvenile type Parkinson's and associated levodopa incited symmetric dyskinesias. A comparison of various surgical alternatives is included. Preoperative and postoperative evaluation, operative method and posteroventral pallidotomy's therapeutic mechanism are presented.

Antiparkinson Agents↗

Small duct cholangitis induced by N-formyl L-methionine L-leucine L-tyrosine in rats.

Primary sclerosing cholangitis (PSC) frequently accompanies inflammatory bowel diseases. In an attempt to increase our understanding of the pathogenesis of PSC, we studied bile duct changes in rats with colitis which had been given N-formyl L-methionine L-leucine L-tyrosine (fMLT) rectally; fMLT is one of the chemotactic peptides produced by Escherichia coli, and is secreted into the bile by hepatocytes after it enters the portal blood. Transrectal administration of fMLT induced a marked inflammation in the portal triad and mild hepatocyte necrosis on the 4th day. The infiltrating leukocytes in the portal tract were mostly mononuclear cells, which densely infiltrated around the bile ducts. These mononuclear cells appeared to attach to bile duct epithelial cells, and they were more numerous in the smaller bile ducts. Electron microscopy revealed that lymphocytes were in direct contact with bile duct lining cells and that some epithelial cells had degenerated or collapsed. These results suggest that this E. coli-derived peptide may induce cholangitis in the small bile duct through cell-mediated mechanisms. Since these pathologic changes resemble those of the bile duct observed in the early stage of PSC, it can be concluded that bacterial chemotactic peptides may play a role in the pathogenesis of small-duct PSC.

Animals↗

NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats, dogs and monkeys.

Phencyclidine (PCP)-induced psychosis is a useful animal model for studies on schizophrenia. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]- ethylamine monohydrochloride (NE-100) had no effect on conditioned avoidance responses (CAR) in rats, whereas, the PCP-induced impairment of avoidance inhibition was attenuated by NE-100. The PCP-induced ataxia or decreased attention in rhesus monkeys was to some extent overcome by NE-100. In dogs, PCP-induced either head-weaving behavior or ataxia, effects which were blocked by NE-100. Administration of PCP led to an increase in beta-2 and a decrease in delta relative power (RP) activity in cortical background spectral electroencephalographics (ECoG) in dogs. While NE-100 in itself showed no significant change in beta-2 and delta RP, NE-100 did block the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effect of PCP in experimental animals. This drug is being considered as a therapeutic for the treatment of patients in the schizophrenia.

Animals↗

Alpha 1-adrenoceptors in human prostate: characterization and binding characteristics of alpha 1-antagonists.

The role of alpha 1-adrenoceptors in the mediation of autonomic functions, particularly in the control of the cardiovascular system, is widely known. It has been shown that alpha 1-adrenoceptors localized in human prostate mediate the contraction of prostatic smooth muscles which produces an increase in the intraurethral pressure and thus, these receptors are important in the regulation of bladder outlet resistance. Alpha 1-antagonists such as prazosin relieve the symptoms of bladder outlet obstruction in men with symptomatic benign prostatic hypertrophy (BPH) by blocking alpha 1-adrenoceptors, thereby decreasing prostatic tone and urethral resistance. Thus, alpha 1-adrenergic stimulation may be one of the most important factors in the development of urinary obstruction in BPH. Alpha 1-adrenoceptors in human prostate have been identified and characterized extensively by functional, radioligand binding and molecular biological techniques. These studies provide evidence in support of the concept that the alpha 1C-subtype forms the majority of alpha 1-adrenoceptors in human prostatic smooth muscles. It has been shown that YM617 (tamsulosin) and naftopidil have higher affinities to alpha 1-adrenoceptors in the prostate than in the aorta. Some alpha 1-antagonists, such as prazosin and terazosin, are not selective with respect to alpha 1-adrenoceptor subtypes, while others, such as 5-methylurapidil and indoramin, show higher potencies for alpha 1C-adrenoceptors and much lower potencies for alpha 1A- and alpha 1B-subtypes. In conclusion, the recent findings from pharmacological and molecular biological studies indicate that selective antagonists of alpha 1C-adrenoceptors could be effective in the treatment of urinary obstruction in symptomatic BPH with fewer cardiovascular side effects.

Adrenergic alpha-Antagonists↗

Gas chromatography/mass spectrometric analysis of 24R,25-dihydroxyvitamin D3 using 24R,25-dihydroxy[6,19,19-2H]vitamin D3 as internal standard.

Gas chromatography/mass spectrometric (GC/MS) analysis of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3, 1a) in rat serum is examined using 6,19,19-trideuterated derivative (24,25-(OH)2[6,19,19-2H]D3, 1c) as an internal standard. Pyro- and isopyro-24,25-(OH)2D3 (2a and 3a) are synthesized and the structures are determined unambiguously by their spectral data including nuclear overhauser enhancement study of the NMR spectra. The two peaks which appear on the total ion chromatogram of 24,25-cyclic n-butyl boronate-3-trimethylsilyl derivative of 24,25-(OH)2D3 are identified to be those of the pyro and isopyro isomers (2a and 3a) by direct comparison with the synthetic standards. Analysis of the GC/MS spectrum of 24,25-(OH)2[6,19,19-2H]D3 (1c) indicated that the CH3(19) is preferentially eliminated in the fragmentation giving rise to a base peak (M-TMSOH-Me)+. Thus the molecular ion peak, which is about 20% of the base peak, rather than the base peak is used for GC/MS assay of 24,25-(OH)2D3 in serum.

24,25-Dihydroxyvitamin D 3↗

Platelet 3H-paroxetine binding in control subjects and depressed patients: relationship to serotonin uptake and age.

3H-paroxetine is regarded as a better ligand for the serotonin (5-hydroxytryptamine; 5-HT) uptake site than 3H-imipramine. In the present study, platelet 14C-5-HT uptake and 3H-paroxetine binding were simultaneously measured in 12 control subjects. There was a significant positive correlation between the individual Bmax value for 3H-paroxetine binding and the Vmax value for 14C-5-HT uptake. Platelet 3H-paroxetine binding was also determined in 21 drug-free patients who satisfied DSM-III-R criteria for major depression and 21 control subjects. A negative correlation was found between the Bmax values for 3H-paroxetine binding with age in control subjects. There was no change in 3H-paroxetine binding in depressed patients compared with control subjects. Our results indicated that 3H-paroxetine was a good ligand for evaluating 5-HT uptake sites, and the influence of age ought to be taken into consideration in the study of 3H-paroxetine binding. The present study indicated that there was no change in 5-HT uptake sites in platelets from depressed patients.

Adult↗

Dynamics of tumor cell clonogen repopulation in a murine sarcoma treated with cyclophosphamide.

Experiments were performed to establish the extent and kinetics of tumor cell repopulation in a murine sarcoma, designated SA-NH, treated with cyclophosphamide (CY). Mice bearing 8-mm leg tumors were treated with 200 mg/kg CY which caused a transient tumor regression. Changes in the absolute clonogen content of tumors was determined by the change in TCD50 values (50% tumor control) obtained under hypoxic conditions of local tumor irradiation at different times after CY treatment until tumors regrew to the pretreatment size. For comparison, hypoxic TCD50 values were determined during the growth of tumors not treated with CY. CY greatly depleted tumors of clonogenic cells as manifested by the reduction in the control TCD50 value of 64.5 Gy to 32.8 Gy 1 day after CY treatment. The reduced TCD50 value remained unchanged for 2 weeks after treatment with CY, at which time the TCD50 began to rapidly increase, continuing until the end of the observation period of 21 days when tumors reached the pretreatment size. In contrast, there was a constant but slower increase in TCD50 values during the growth of tumors not treated with CY. The daily increase in TCD50 was more than twice as high in CY-treated than in CY-untreated tumors: 4.5 Gy/day versus 2.1 Gy/day. This implies that the rate of clonogen production in CY-treated tumors was twice as high as that of unperturbed tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Validation of continuous wave Doppler-determined right ventricular peak positive and negative dP/dt: effect of right atrial pressure on measurement.

OBJECTIVES: The present study aimed to validate the peak positive and negative values of the first derivative of right ventricular pressure (dP/dt) using Doppler echocardiography and to determine the impact of right atrial pressure on the measurements. BACKGROUND: A pressure gradient between the right ventricle and the right atrium can be obtained by continuous wave Doppler-derived tricuspid regurgitant velocity using the simplified Bernoulli equation. If right atrial pressure fluctuation during systole and isovolumic diastole were small compared with right ventricular pressure changes, right ventricular pressure could be evaluated, and maximal positive and negative dP/dt could also be determined with Doppler echocardiography. METHODS: We investigated 11 patients with a wide range of right atrial pressure with tricuspid regurgitation using simultaneous examination by Doppler ultrasound and catheterization. Hemodynamic conditions were altered by the Valsalva maneuver, and a total of 40 beats were analyzed. RESULTS: There was good correlation between Doppler-derived and catheterization-derived peak positive dP/dt (y = 1.0x - 15.4, r = 0.98, n = 40), irrespective of the level of right atrial pressure. Doppler-derived peak negative dP/dt also showed good correlation with that determined by catheterization (y = 0.9x + 58.2, r = 0.93, n = 40). However, in patients with high right atrial pressure (v wave pressure > or = 10 mm Hg), Doppler-derived peak negative dP/dt tended to show lower values than those from catheterization measurements, except in patients with pulmonary hypertension. CONCLUSIONS: We conclude that right ventricular dP/dt can be estimated by the Doppler method accurately and noninvasively. However, when right atrial pressure is relatively high compared with corresponding right ventricular pressure changes during isovolumic diastole, Doppler-derived peak negative dP/dt might underestimate catheter-derived measurements.

Adult↗

Investigation of tumor invasion with [111In]antimyosin.

Accumulation of [111In]antimyosin in various types of tumors has been reported. In order to test the possibility that the destruction of muscle tissue by tumor invasion could induce high uptake of [111In]antimyosin, we investigated the distribution of [111In]antimyosin in tumor and muscle using autoradiography (ARG). High uptake of [111In]antimyosin was observed both in rabbit papilloma VX2 and rat hepatoma AH109A by scintigraphy and tissue distribution studies, and its concentration was found to be highest at the periphery and outer surface of the tumors using whole-body ARG. However, in micro- and macro-ARG, high grain density was observed in granulation tissue with macrophage infiltration between the tumor and muscle, not in the muscle tissue invaded by tumor cell. Significant non-specific accumulation of [111In]antimyosin in inflammatory tissue surrounding the tumor was suggested.

Animals↗

Ascites sarcoma 180, a tumor associated with hypercalcemia, secretes potent bone-resorbing factors including transforming growth factor alpha, interleukin-1 alpha and interleukin-6.

Ascites sarcoma 180 (S180A) is a transplantable tumor which causes hypercalcemia in tumor-bearing mice, and stimulates bone resorption without parathyroid hormone-like activity. In the present study, parathyroid hormone-related protein (PTHrP) mRNA could not be detected in total RNA from S180A cells. Bone-resorbing activity (BRA) derived from serum-free conditioned medium of S180A cells (S180A-CM) was coeluted with either transforming growth factor alpha (TGF alpha) activity (peak A, approximate M(r), 29 kDa) or lymphocyte-activating factor (LAF) activity (peak B, M(r), 20.1-24 kDa) in Bio-Gel P-100 column chromatography. Fractions in peak A and B contained IL-6 but not tumor necrosis factor alpha (TNF alpha). Subsequent separation of peak A by reverse-phase high performance liquid chromatography produced a single fraction which contained both BRA and TGF alpha activity. Recombinant human TGF alpha-induced bone resorption was completely inhibited by indomethacin. The BRA in peak A was partially inhibited by indomethacin and almost completely inhibited by simultaneous treatment of indomethacin and anti-IL-6 antibody. The BRA in peak B was partially inhibited by neutralization with anti-IL-1 alpha antibody and was completely inhibited by simultaneous treatment with anti-IL-1 alpha and anti-IL-6 antibody in the absence of indomethacin. Bone resorption induced by S180A-CM was associated with an increased production of prostaglandin E2 (PGE2) by calvaria. The BRA in S180A-CM, however, was not completely abolished by the simultaneous addition of indomethacin and anti-IL-1 alpha, anti-IL-1 beta and anti-IL-6 antibodies. Our findings indicate that (1) BRA derived from S180A cells includes TGF alpha, IL-1 alpha, IL-6 and some other unknown factor(s), distinct from PTHrP, IL-1 beta and TNF alpha, and (2) these unknown factors resorb bone in part via a PGE2-independent pathway.

Animals↗

Effects of nerve growth factor and dexamethasone on Na+,K(+)-ATPase of cultured PC12h cells.

When PC12h cells were cultured for 4 days in the presence of 50 ng/ml of nerve growth factor (NGF), they showed elongated dendrites and specifically increased Na+,K(+)-ATPase activity. Either singly or in combination with NGF, dexamethasone also increased the specific activity of this enzyme. Western blot analysis using anti-alpha 1 and anti-alpha 2 antisera showed that PC12h cells, either before or after hormone treatment, contained the alpha 1 isoform but not the alpha 2 one. We conclude, therefore, that NGF induces Na+,K(+)-ATPase concomitantly with neuronal differentiation in PC12h cells but that the growth factor does not induce formation of the myelin sheath, which normally expresses the alpha 2 isoform of Na+,K(+)-ATPase.

Animals↗

Laparoscopic radical nephrectomy for renal cell carcinoma: early experience.

We developed a laparoscopic radical nephrectomy for malignant disease of the kidney and successfully performed the operation in six patients between July 1992 and October 1993. This procedure is basically derived from that of Clayman and associates. A CO2 pneumoperitoneum is induced, and five trocars are introduced into the abdominal cavity through the lateral abdominal wall. The kidney is removed en bloc together with the adrenal gland, perirenal fatty tissue, and Gerota's fascia. The free kidney is put into a laparoscopy sack, and the sack is pulled out through a 5- to 6-cm incision in the abdominal wall without morcellation to allow complete pathologic examination. By this procedure, right nephrectomy was performed in four patients and left nephrectomy in two patients. The mean operative time was 6 hours and 13 minutes, and the mean blood loss was 430 mL. There were no severe complications. The average hospital stay was 11 days, and the average time to full convalescence was 21 days. Pathologic examination revealed renal cell carcinoma in five patients and nephroblastoma in one. Of the patients with renal cell carcinoma, the stage was pT1pN0pM0 in three patients and pT2pN0pM0 in two. There has been no recurrent disease in these six patients with a mean follow-up period of 9.5 months.

Adult↗

Structural studies on the tri- and tetrasaccharides isolated from porcine intestinal heparin and characterization of heparinase/heparitinases using them as substrates.

We prepared a series of oligosaccharides from porcine intestinal heparin after extensive digestion with a mixture of Flavobacterium heparinase as well as heparitinases I and II. Previously, we reported the structures of the two glycoserines derived from the carbohydrate-protein linkage region [Sugahara et al., J. Biol. Chem., 267, 1528-1533 (1992)] and three tetrasaccharides derived from the antithrombin III-binding site [Yamada et al., J. Biol. Chem., 268, 4780-4787 (1993)]. In this study, we determined the structures of 10 other tetrasaccharides and a trisaccharide by enzymatic digestion, fast atom bombardment mass spectrometry and 500-MHz 1H NMR spectroscopy. These tetrasaccharides share the common disulphated structure, delta HexA alpha 1-4GlcN(N-sulphate)alpha 1-4IdoA(2-sulphate)alpha 1-4GlcN (where HexA is hexuronic acid and IdoA is L-iduronic acid), and their structural variations are based upon the positions of additional sulphate groups. Eight among the 10 have never been isolated as discrete structures. The structure of the trisaccharide is GlcN(N-sulphate)alpha 1-4IdoA(2-sulphate) alpha 1-4GlcN(N,6-disulphate) and is derived from the non-reducing terminus of heparin chains. This structure may represent the terminus of a biosynthetically formed native heparin chain or a newly formed non-reducing terminus exposed by a tissue endo-beta-glucuronidase which may be involved in the intracellular post-synthetic fragmentation of macromolecular heparin. The 11 structures characterized in the present study and 6 additional tetrasaccharides were used to investigate the substrate specificities of heparinase, as well as heparitinases I and II. The results indicate that modification of the adjacent glucosamine on the reducing side of the disaccharide cleavage site influences the enzymatic action of the lyases, whereas the adjacent uronic acid on the non-reducing side is not recognized by these enzymes.

Animals↗

Structural studies on the oligosaccharides isolated from bovine kidney heparan sulphate and characterization of bacterial heparitinases used as substrates.

We prepared a series of oligosaccharides from commercial bovine kidney heparan sulphate after limited digestion with heparitinase I from Flavobacterium heparinum, and determined the structures of eight tetrasaccharides and a hexasaccharide by enzymatic analysis, fast atom bombardment mass spectrometry and 500 MHz 1H NMR spectroscopy. The tetrasaccharides share the common core structure delta 4,5HexA alpha 1-4GlcN alpha 1-4HexA1-4GlcN (where delta 4,5HexA is 4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid and HexA is hexuronic acid), with zero, one or two sulphate groups. Seven of them contain non-sulphated glucuronic or iduronic acid, and the other, 2-O-sulphated iduronic acid at the internal position. Although they contain ordinary structures which should be widely distributed in the relatively low-sulphated region of heparan sulphate, five of the tetrasaccharides were isolated for the first time as discrete structures. The structure of the hexasaccharide was determined as delta 4,5HexA alpha 1-4GlcNAc alpha 1-4GlcA beta 1-3Gal beta 1-3Gal beta-1-4 Xyl and is derived from the carbohydrate-protein linkage region of the heparan sulphate chains. The hexasaccharide seems to have been released by the alkaline treatment used to prepare the heparan sulphate. The Gal residues were non-sulphated as are those in the porcine intestinal heparin chains, but in contrast to the sulphated Gal structures previously demonstrated in the carbohydrate-protein linkage region of chondroitin sulphate chains. These oligosaccharides were used to investigate the substrate specificity of heparitinases I and II from F. heparinum. The results revealed that heparitinase I cleaves hexosaminidic bonds linked to non-sulphated glucuronic or iduronic acid residues. The glucosaminidic linkage of the hexasaccharide was sensitive to heparitinase I, but resistant to heparitinase II, demonstrating the differential specificity of these enzymes towards the carbohydrate-protein linkage region.

Animals↗

Effects of cross-linking of membrane proteins on vesiculation induced by dimyristoylphosphatidylcholine in human erythrocytes.

To study the effect of cross-linking of membrane proteins on vesiculation of human erythrocytes by dimyristoylphosphatidylcholine (DMPC), red cells were treated with diamide at atmospheric pressure or 100 MPa and then incubated with DMPC in buffers of pH 6.5-8.5. Irrespective of buffer pH, the amount of released vesicles increased upon cross-linking of membrane proteins but approached the control level upon reduction of the cross-linking by dithiothreitol. Similar enhancement of vesicle release was also observed in N-ethylmaleimide-treated red cells. Hemolysis during vesiculation was observed only in red cells treated with diamide at 100 MPa. Furthermore, the composition of membrane proteins in released vesicles was analyzed by SDS-PAGE. Membrane vesicles released from intact red cells or the cells treated with diamide at atmospheric pressure contained band 3 as a major membrane protein. On the other hand, membrane vesicles from red cells treated with diamide at 100 MPa contained protein 4.1 in addition to band 3 and the orientation of these proteins was similar to that in intact cells. These results indicate that the amount and membrane protein composition of DMPC-induced vesicles are much affected by chemical modification of SH-groups in red cell membrane proteins.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗