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Biomedical subjects

S Kubo

Publications and source records attributed to S Kubo.

At least 217 records · Page 12Linked to original sources
PubMed1995

T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thymic selection: requirement of calcineurin activation for thymic positive selection but not negative selection.

The goal of this study was to identify the differences of intracellular signals between the processes of thymic positive and negative selection. The activation of calcineurin, a calcium- and calmodulin-dependent phosphatase, is known to be an essential event in T cell activation via the T cell receptor (TCR). The effect of FK506, an inhibitor of calcineurin activation, on positive and negative selection in CD4+CD8+ double positive (DP) thymocytes was examined in normal mice and in a TCR transgenic mouse model. In vivo FK506 treatment blocked the generation of mature TCRhighCD4+CD8- and TCRhighCD4-CD8+ thymocytes, and the induction of CD69 expression on DP thymocytes. In addition, the shutdown of recombination activating gene 1 (RAG-1) transcription and the downregulation of CD4 and CD8 expression were inhibited by FK506 treatment suggesting that the activation of calcineurin is required for the first step (or the very early intracellular signaling events) of TCR-mediated positive selection of DP thymocytes. In contrast, FK506-sensitive calcineurin activation did not appear to be required for negative selection based on the observations that negative selection of TCR alpha beta T cells in the H-2b male thymus (a negative selecting environment) was not inhibited by in vivo treatment with FK506 and that there was no rescue of the endogenous superantigen-mediated clonal deletion of V beta 6 and V beta 11 thymocytes in FK506-treated CBA/J mice. DNA fragmentation induced by TCR activation of DP thymocytes in vitro was not affected by FK506. In addition, different effects of FK506 from Cyclosporin A on the T cell development in the thymus were demonstrated. The results of this study suggest that different signaling pathways work in positive and negative selection and that there is a differential dependence on calcineurin activation in the selection processes.

Animals↗
PubMed1995

Solution structure of omega-conotoxin MVIIC determined by NMR.

The solution structure of the P- and Q-type Ca2+ channel blocker, omega-conotoxin MVIIC (a peptidic neurotoxin composed of 26 amino acid residues), has been determined by 1H-NMR and simulated annealing calculations. The resulting calculated structures converged very well to a conformation with an average value of pairwised RMSD for N, C alpha and C' of 0.62 A. Lys-25 is buried in the molecule and less flexible so that among the four Lys residues, its side chain provides the lowest reactivity on biotinylation and the mono-biotinylation in this residue less influences the biological activity.

Amino Acid Sequence↗
PubMed1995

Neurohumoral variability in left ventricular dysfunction. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

The immediate and longer term variability of selected vasoactive- and volume-regulating neurohormones were measured in patients entering a substudy of the Studies of Left Ventricular Dysfunction--a randomized clinical trial in patients with left ventricular ejection fraction < or = 35%. The variability of these hormones has not been determined in a large cohort of patients. Immediate (short-term) variability was assessed by systematically comparing levels after 15 and 30 minutes of supine rest at the initial visit, and longer term variability was assessed by comparing 30-minute supine rest values at the initial visit with corresponding values taken at 30 minutes after 16 to 24 days of stable therapy. Initial values obtained at the first visit after 30-minute supine rest for all 209 patients were (mean +/- SEM) 512 +/- 21 pg/ml pg/ml for plasma norepinephrine, 1.9 +/- 0.2 ng/ml/hr for plasma renin activity, 3.0 +/- 0.1 pg/ml for plasma arginine vasopressin, and 129 +/- 5.3 pg/ml for plasma atrial natriuretic peptide. All variables were moderately increased relative to established normal values. There was a small but significant decrease from 15- to 30-minute supine posture in all neurohormones, except arginine vasopressin. In the presence of stable background therapy, no significant differences were found between measurements obtained after 30 minutes supine rest at the initial visit and 16 to 24 days later. Spearman correlation coefficients corresponding to immediate and longer term variability were high (range 0.55 to 0.79) (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Effect of prednisolone on ascending renal infection due to biofilm disease and lower urinary tract obstruction in rats.

A model of renal infection due to lower urinary tract obstruction and biofilm disease was constructed for the study of renal scarring by inserting glass beads coated with bacterial biofilm into the bladder of rats and then clamping the urethra. We previously reported the effect of antimicrobial therapy used in combination with the anti-inflammatory agent prednisolone to prevent renal scarring. In this study we investigated the effect of prednisolone on renal scar formation using our new model. Renal scarring could not be prevented in the group in which prednisolone was administered in the period during which the urethra was regularly being clamped. In contrast, scarring was prevented in the group that began to receive prednisolone after the period of clamping had ended. Therefore, in cases of lower urinary tract obstruction prednisolone should only be administered for the prevention of renal scarring after the obstruction has been resolved.

Animals↗
PubMed1995

Transesophageal echocardiography in the diagnosis of thoracic saccular aortic aneurysm. The value of transesophageal echocardiography during the course of treatment.

Transesophageal echocardiography (TEE) was performed in 17 cases of aortic aneurysms referred to our hospital for further examination and treatment. All 17 cases were treated surgically and TEE was performed as a preoperative examination. In nine of the 17 cases, there were already some signs of bleeding upon admission and in all of these nine cases, rupture of the aneurysm was confirmed during surgery. Measurement on cross-sectional TEE imaging disclosed large aneurysmal diameters in eight of these nine cases, suggesting a close relationship between diameter and rupture. Moreover, observation of the lesions by TEE suggested a relationship between the risk of rupture and morphological characteristics of the thrombus. In seven of the nine bleeding cases, TEE imaging revealed destructive features of the aneurysmal thrombus, such as exfoliation from the aortic wall and/or tearing-off, suggesting expansion of the aortic diameter. Detailed findings of the aneurysm and thrombus on TEE corresponded with surgical findings. Thus, we concluded that TEE is a useful method of obtaining information about aortic aneurysms not only as a preoperative examination but also as an independent examination to determine treatment options and prognosis.

Aged↗
PubMed1995

Preventive effect of ulinastatin on renal scarring in rat model of pyelonephritis induced by direct or ascending infection with Serratia marcescens or Escherichia coli.

Renal scarring is considered to be a characteristic of reflux nephropathy. The effects of ulinastatin, a strong inhibitor of polymorphonuclear leukocyte elastase, on renal scarring following direct parenchymal or intravesical ascending infection by Serratia marcescens or Escherichia coli were determined. Four days of treatment with ulinastatin initiated 2 or 5 days after infection prevented renal scarring. Doses of 1,000-4,000 units/kg inhibited renal scar formation, but 8,000 units/kg did not. These results suggest that it may be possible to limit renal scar formation in pyelonephritis by the use of an appropriate pharmacologic agent.

Animals↗
PubMed1995

Interpretation of extravascular thermal volume of the lung in patients with chronic pulmonary diseases.

To understand the significance of measured extravascular thermal volume of the lung (ETVL) in chronic pulmonary diseases, we measured ETVL using the double-indicator dilution technique in 17 emphysematous patients and 15 patients with pulmonary fibrosis. The level of ETVL in emphysema is significantly correlated with parameters reflecting the severity of the disease, including FEV1.0% (r = 0.54, p < 0.05), DLCO/VA (r = 0.54, p < 0.05), PaO2 (r = 0.61, p < 0.01), and mean pulmonary artery pressure (r = -0.61, p < 0.01). In pulmonary fibrosis, a significant inverse correlation was found between ETVL and PaO2 (r = -0.64, p < 0.02), DLCO/VA (r = -0.58, p < 0.05), and %VC (r = -0.61, p < 0.02). The mean level of ETVL in both groups of patients was lower than previously reported normal values. These results suggest that ETVL may reflect the decrease in pulmonary vasculature in emphysematous patients, while it may signify a decrease of pulmonary vasculature and increased volume of pulmonary interstitial tissue surrounding the pulmonary vasculature in pulmonary fibrosis. We conclude that ETVL may represent a good estimate of the condition of the pulmonary vasculature and interstitial tissue volume in patients with chronic pulmonary diseases.

Aged↗
PubMed1995

The ultrastructure, kinetics and intralobular distribution of apoptotic hepatocytes after portal branch ligation with special reference to their relationship to necrotic hepatocytes.

Apoptosis was originally defined as shrinkage necrosis, as a distinct mode of cellular death from coagulative necrosis in the rat liver lobes after portal branch ligation. To reveal the functional role of the apoptosis of hepatocytes in the volume reduction and recovery of normal hepatic architecture in portal-deprived liver lobes, we ligated the portal vein branch supplying the left and median liver lobes in Wistar rats. The liver lobes were perfusion-fixed with glutaraldehyde solution via the proximal site of the ligated portion of the portal vein on Days 1, 2, 4, 7 and 14 after operation and examined light and electron microscopically. On Day 2 after ligation, massive necrosis of hepatocytes occurred in the central to intermediate zones of the liver lobule, and apoptotic hepatocytes were observed in the boundary region between necrotic and normal areas. Such necrotic area-associated apoptosis of hepatocytes was most frequent on Day 2, declining thereafter. The sequential changes of the cell organelles in apoptotic hepatocytes were distinct from those in necrotic hepatocytes. On Day 7, when necrotic areas had almost disappeared the apoptosis of hepatocytes occurred mostly between intact hepatocytes in the "combined hepatic cell cords" which included no obvious sinusoidal lumen between hepatic cell cords. Such necrotic area-nonassociated apoptosis began to increase in frequency on Day 4, reached a peak on Day 7 and was gone by Day 14, when normal hepatic architecture was recovered. The present study suggests that both necrotic area-associated and non-associated apoptosis of hepatocytes may be induced by mild ischemia and contribute in part to the volume reduction of ligated liver lobes. It further reveals that the necrotic area-non-associated apoptosis of hepatocytes plays a role in reconstructing the architecture of hepatic cell cords after necrotic hepatocytes have undergone dissolution in the liver lobule.

Animals↗
PubMed1995

Effect of pili of Serratia marcescens on superoxide production and phagocytosis of human polymorphonuclear leukocytes.

PURPOSE: To determine the role played by superoxide in renal scar formation following renal infection. MATERIALS AND METHODS: The piliation of bacteria was assessed for its capacity to interact with human polymorphonuclear leukocytes (PMNs). Two recombinant strains having either MS or MR pili of Serratia marcescens were constructed. RESULTS: The MS-piliated strain stimulated superoxide production of PMNs twice as much as the MR- or nonpiliated strains did. The MS-piliated strain was more susceptible to phagocytosis than was the MR- or nonpiliated strain. CONCLUSION: These data suggest that the MS-piliated strain stimulates superoxide production of PMNs associated with phagocytosis, which leads to tissue damage in infected organs.

Drug Resistance, Microbial↗
PubMed1995

Portography in decision-making about indications for liver resection in hepatolithiasis.

We studied the findings of portograms of patients with hepatolithiasis and the role of portography in decision-making about indications for hepatic resection. The subjects were 20 patients in whom hepatic arteriography including the portal phase or percutaneous transhepatic portography was done. We studied the relationships between the findings of the portograms and cholangiograms and hepatic atrophy or associated cholangiocarcinoma. The portal vein in the involved segment of the liver was obstructed in nine patients, and these patients had hepatic atrophy with or without cholangiocarcinoma. There were 16 patients with hepatic atrophy. Four of five other patients in whom protal shrinking was seen had hepatic atrophy. Bile ducts in the involved segment were obstructed in six patients with hepatic atrophy. In all five patients with cholangiocarcinoma, there was portal obstruction at the branching point in the hepatic hilum, with obstruction of the bile ducts at the same point in two of these patients. Hepatic atrophy and cholangiocarcinoma was more closely associated to changes of the portal vein than obstruction of the bile ducts. Portography is useful to diagnose hepatic atrophy and cholangiocarcinoma and for decision-making about indications for hepatic resection in hepatolithiasis.

Adult↗
PubMed1995

Case of hepatolithiasis diagnosed by magnetic resonance cholangiography.

We report a case of hepatolithiasis in which cholangiography by magnetic resonance (MR) imaging was useful in making a detailed diagnosis. Sonograms showed a high echoic lesion in the liver, and computed tomograms showed dilated intrahepatic bile ducts and atrophic hepatic tissue. By ordinary cholangiography, these findings were not made because of obstruction of the bile ducts by the stones. In MR cholangiograms, intrahepatic stones in dilated bile ducts in the posterior segment were seen, as were dilated bile ducts in the peripheral part of this segment. Posterior segmentectomy was done. The operative specimens had stones in the dilated bile ducts, and hepatic tissue was atrophic. MR cholangiography is useful to diagnose not only hepatolithiasis but also dilatation in the bile ducts. MR cholangiography should be tried if other examinations do not give sufficient information.

Calculi↗
PubMed1995

[An autopsy case of traumatic subdural hematoma from arterio-venous malformation with diffuse axonal injury].

Diffuse axonal injury (DAI) is defined as widespread damage to axons in the white matter of the brain without focal injury such as contusion and acute subdural hematoma. A case of traumatic subdural hematoma from arterio-venous malformation accompanied by DAI is reported. A 58-year-old man was assaulted, and immediately lost consciousness, and remained unconscious during about 44 hours until his death. The autopsy revealed acute subdural hematoma (about 160 g) on left temporal lobe and left cingular, uncal and cerebellar tonsillar herniation, and tear and hemorrhage of the corpus callosum. Under this subdural hematoma, gray-whitish vascular lesion with subarachnoid hemorrhage was found. Histologically, this lesion was diagnosed as the arterio-venous malformation. Neuropathological examination of the corpus callosum, dorsolateral part of midbrain and superior cerebellar peduncle revealed DAI findings, such as swelling and ballooning of the myelin fibers, swelling and waving of axons, and retraction balls. Axon degenerations were also observed immunohistochemically by anti-200 kD neurofilament antibody. From the results, his unconsciousness from the moment of impact might be occurred from not only subdural hematoma but also DAI.

Axons↗
PubMed1994

Induction of Ly-49 on an interspecies hybridoma between differentiation stage specific murine T cells and a rat T lymphoma.

Ly-49 can be expressed in interspecies hybridoma cells resulting from the fusion of Ly-49 negative lymphoid cells from normal mice and Ly-49 negative T cells from the rat thymoma W/Fu(C58NT)D (C58). Several hundred hybridoma clones of this type were studied. Hybridoma clones derived from the fusion between activated C57BL/6 mouse spleen cells and C58 expressed Ly-49 on their surface although Ly-49 was undetectable on both parental cells. No Ly-49 antigen was expressed on hybrids when BW5147, a T lymphoma derived from AKR mouse, replaced C58 as parental cell. Thymocytes from C57BL/6 mice also produced Ly-49 positive interspecies hybridomas with C58. Subsequent manipulation of these thymocytes with a mixture of anti-CD4 and anti-CD8 antibodies plus complement to obtain double negative cells (CD4-/CD8-) prior to the fusion abolished the expression of Ly-49 on hybridomas. On the other hand, if the thymocytes were treated with either anti-CD4 or anti-CD8 antibody plus complement, the resultant thymocytes which were a mixture of cells with a single positive (CD4+/CD8- or CD4-/CD8+) and a double negative phenotype (CD4-/CD8-) retained the ability to produce Ly-49 positive hybridomas. Interspecies hybridomas between either CD4+/CD8- or CD4-/CD8+ functional T cell clones and C58 expressed Ly-49 on their surface, though these parental T cells lacked Ly-49 on their surfaces. Northern hybridization analysis using Ly-49 cDNA revealed that C58 cells do not express Ly-49 mRNA, indicating that a trans-acting factor(s) from C58 plays an important role in the induction of cell surface Ly-49 expression on interspecies hybridomas. Our data indicate the complex nature of the regulatory mechanisms for expression of the Ly-49 molecule.

Animals↗
PubMed1994

Studies of human granulocyte phagocytosis stimulation by tuftsin.

Tuftsin (Thr-Lys-Pro-Arg), a natural immunomodulating peptide originally found to stimulate phagocytosis by polymorphonuclear leukocytes (PMNs), is now known to bind to both PMNs and monocyte-macrophages, affecting their phagocytosis and other functions. The potential roles of tuftsin in surgery-related infections have been documented using animal models. However, there have been some difficulties in demonstrating the phagocytosis-stimulating activity of tuftsin. In view of this, we have developed a suitable human PMN phagocytosis assay for tuftsin and performed preliminary kinetic studies. The assay was performed on 24-well plates between PMNs and fluorescent microspheres. The greatest effect of tuftsin over the control was observed under the following conditions: 15 min incubation at 37 degrees C with 5 micrograms/ml tuftsin and a 50:1 ratio of particle to PMN. Particles bound on the surface of PMNs were removed by washing and trypsin treatment, followed by centrifugation through fetal bovine serum. This allowed us to utilize flow cytometry in this study. A flow cytometric procedure was then successfully adapted to human PMN phagocytosis that established a high correlation between microscopic evaluation and flow cytometry of phagocytosis. In addition to the above determinations of the percentage of phagocytic cells, we evaluated the effect of tuftsin on the number of particles engulfed by PMNs. Under the above optimum conditions, tuftsin has greater impact on the number of particles engulfed than on the percentage of phagocytic cells.

Amino Acid Sequence↗