Injury to the skin induces p53- and Fas-dependent bystander keratinocyte apoptosis in vivo.
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Animals↗
Biomedical subjects
H Matsushima
Publications and source records attributed to H Matsushima.
Sensitive determination of pethidine in body fluids by surface ionization organic mass spectrometry.
We have presented a simple and sensitive method for determining pethidine, a narcotic analgesic drug in body fluids by gas chromatography (GC)/surface ionization organic mass spectrometry (SIOMS). Good linearity was obtained in the range of 0.625-25 ng/ml of whole blood and urine by mass chromatography, and in the range of 0.05-2 ng/ml of whole blood by selected ion monitoring (SIM). Pethidine and diphenylpyraline (internal standard) were extracted from body fluids with Bond Elut Certify cartridges; their recoveries were above 95%. The detection limits (signal-to-noise ratio=3) were estimated to be 0.2 ng/ml of whole blood or urine by mass chromatography, 0.02 ng/ml of whole blood by SIM.
Analgesics, Opioid↗
Differences in anti-LKM-1 autoantibody immunoreactivity to CYP2D6 antigenic sites between hepatitis C virus-negative and -positive patients.
Anti-liver kidney microsome type 1 autoantibodies (anti-LKM-1) are known to be present in sera of autoimmune hepatitis type II and a subset of chronic hepatitis C patients. The autoantigen to anti-LKM-1 has been identified to be cytochrome P450 IID6 (CYP2D6) and the most frequently cited CYP2D6 antigenic sites of anti-LKM-1 in sera from autoimmune hepatitis type II patients spans the region aa 256-269. Other antigenic sites on CYP2D6 exist and have been identified in the two patient groups. However, most of these sites are concentrated on the carboxyl-terminal side of the protein, and the amino-terminal region has not been thoroughly investigated. Here, we have studied the antigenicity of the CYP2D6 amino region and compared reactivities between hepatitis C virus (HCV)-negative and -positive Japanese patient groups. A total of 34 anti-LKM-1-positive sera (eight with autoimmune hepatitis type II and 26 with chronic hepatitis C) were included. The immunoreactivity of patients' sera was examined against four conformational and one linear CYP2D6 peptide fragments. A defined antigenic site spanning aa 181-245 was found to react with 88% (7/8) of autoimmune hepatitis type II patients, as opposed to only 38% (10/26) of chronic hepatitis C patients. This was a significant difference (P< 0.043). Among these positively reacting samples, five of the seven autoimmune hepatitis type II sera and four of the ten chronic hepatitis C sera also reacted with a synthetic peptide spanning aa 256-269. Anti-LKM-1 thus may be able to recognize simultaneously at least two antigenic sites on the CYP2D6 protein, and reactivities against individual epitopes may differ according to HCV infectivity status.
Adult↗
Differences in cell kinetic changes among renal cancer cell lines treated with interferon-alpha.
BACKGROUND: Interferon (IFN)-alpha shows certain clinical effects on the treatment of renal cell carcinoma. The purpose of the present study was to investigate its direct effects and to compare the responses among different human renal cancer cell lines. METHODS: Three cell lines, ACHN, RCC10RGB and OS-RC-2, were incubated with IFN-alpha and evaluated using MTT assay for cell proliferation and two-color flow cytometry for cell-cycle-specific cyclin expressions coupled with DNA ploidy analysis. RESULTS: Interferon-alpha inhibited cell proliferation and caused cell accumulation at S and G2/M phases. However, IFN-alpha induced no significant change in cyclins D1, E, A or B1 expression. Interestingly, cell kinetic changes caused by IFN-alpha were different among cell lines. Cell proliferation was suppressed most in ACHN, then RCC10RGB and least in OS-RC-2. Comparing DNA histograms, ACHN showed distinct increase of G2/M cells associated with elevation of late S cells. RCC10RGB showed a predominant increase of whole S cells accompanied with a slight increase of G2/M. OS-RC-2 showed a modest increase of S cells with a little change of G2/M cells. Chronological observation revealed that S-phase increase and proliferative inhibition appeared on day 1 and day 3, respectively, in ACHN and RCC10RGB, and on day 5 in OS-RC-2. CONCLUSIONS: Interferon-alpha induced substantial cell kinetic interference directly in the tested human renal carcinoma cell lines. The degree of change was different according to the nature of the cell line. It may partly indicate the variety of the efficacy of IFN-alpha treatment against renal cancers.
Carcinoma, Renal Cell↗
Complication of oliguric acute renal failure in patients treated with low-molecular weight dextran.
Acute renal failure (ARF) is a well-documented but infrequent complication in patients treated with low-molecular weight dextran (LMWD). We herein report 3 cases of oliguric ARF following the administration of dextran-40. One case developed ARF totally after 1.200 g of LMWD administration. In contrast, two cases having increased serum creatinine developed oliguria despite the acceptable therapeutic doses (totally 450 and 650 g). Contrast media was also co-administered in these patients. Plasma exchange (PE), double filtration plasmapheresis (DFPP), or continuous hemodiafiltration (CHDF) but not hemodialysis (HD) reduced circulating dextran concentrations by 35-44% during a single session. All patients completely recovered from ARF by 14-32 days after the treatment. Our cases suggested that radiocontrast could predispose to the development of LMWD-induced ARF especially in patients having pre-existing renal dysfunction. In addition, PE, DFPP and CHDF afforded a beneficial effect for removing accumulated LMWD from the circulation.
Acute Kidney Injury↗
Up-regulated TGF-beta mRNA expression in splenic T cells of high IgA-prone mice: a murine model of IgA nephropathy with glomerulosclerosis.
BACKGROUND/AIMS: Recently, we established a high serum IgA-prone inbred (HIGA) mouse strain as a murine model of spontaneous IgA nephropathy by selective mating of high serum IgA ddY mice, and found that they showed enhanced production of glomerular extracellular matrix components with increased expression of TGF-beta mRNA and protein in the kidneys. In this study, we examined the roles of lymphocytes in the development of high serum IgA in this strain. METHODS: We performed flow cytometric analyses of T and B cells in splenic mononuclear cells (SMNCs) from these mice using BALB/c mice as normal controls. We also compared serum TGF-beta1 concentrations and TGF-beta mRNA expression levels in the B-cell-depleted (T-cell-rich) fraction of SMNCs in these mice. RESULTS: HIGA mice showed significantly fewer CD3-positive cells compared with BALB/c mice when young, but not when aged. The CD4/CD8 ratio of HIGA mice was lower than that of BALB/c mice, but this difference was not significant. Although the number of B220-positive cells did not vary significantly, the ratio of surface IgA-positive B cells was significantly increased in both young and adult HIGA mice. The B-cell-depleted SMNCs from HIGA mice exhibited higher levels of expression of TGF-beta and TGF-beta1 mRNA than controls from a young age, which were maintained throughout life, but there were no differences in PDGF, MCP-1 or bFGF expression between these two strains. In contrast to local mRNA expression, serum TGF-beta1 concentration was decreased in HIGA mice compared with BALB/c controls. CONCLUSION: These findings suggest that the mating procedure performed to establish HIGA mice selected for a unique phenotype of local up-regulation of TGF-beta production in the kidneys, as well as T cells that may contribute to both the early and consistently high serum IgA expression and enhanced production of renal extracellular matrix components in HIGA mice. Additionally, TGF-beta1 may act locally, not systemically, in a paracrine or autocrine manner.
Animals↗
Pharmacological effect of tamsulosin in relation to dog plasma and tissue concentrations: prostatic and urethral retention possibly contributes to uroselectivity of tamsulosin.
In the present study the pharmacokinetics and pharmacodynamics of tamsulosin were investigated in anesthetized male dogs. Hypogastric nerve stimulation elevated the intraurethral pressure (IUP), which was inhibited dose dependently by intraduodenal administration of tamsulosin (3-30 microg/kg). The inhibition peaked about 90 min after dosing and lasted up to 240 min. The basal mean blood pressure did not change significantly during the observation period. The plasma, prostatic, and urethral concentrations of tamsulosin were determined by the liquid chromatography-mass spectrometry/mass spectrometry method. The plasma concentration reached the maximal level within 30 min after dosing and gradually declined thereafter. The maximal total plasma concentration of tamsulosin (C(max, t)) and its unbound concentration (C(max, u)) correlated with the maximal effect on IUP response [r(2) = 0.81 (p<0.01, n = 15) and r(2) = 0.84 (p<0.01, n = 15), respectively]. Each individual unbound plasma concentration did not correlate, however, with its associated inhibition of IUP response (r(2) = 0.04, n = 126). Although the plasma concentration of tamsulosin decreased nearly to the lower limit of quantitation 240 min after dosing, the prostatic and urethral concentrations remained high, i.e., 13 to 44 times greater than the plasma concentration. Our data demonstrate that the maximal inhibition by tamsulosin of IUP response is well correlated with the maximal plasma concentration in the early phase. The sustained effect of tamsulosin on IUP response that follows may be related to prostatic and urethral retention of tamsulosin.
Adrenergic alpha-Antagonists↗
[A case of drug-induced interstitial pneumonitis in rheumatoid arthritis treated with bucillamine].
We report a case of bucillamine-induced interstitial pneumonitis in a 57-year-old woman. Rheumatoid arthritis was diagnosed in May 1999, and she was treated with bucillamine from June 1999, with a favorable outcome. After complaining of cough, fever, and dyspnea in October, she was admitted to this hospital. Blood gas analysis showed severe hypoxemia. The chest CT revealed both bilateral diffuse ground-glass opacity along the bronchovascular bundles, and thickening of the interlobular septa. We suspected bucillamine-induced interstitial pneumonitis from the findings of the CT scan, BALF and TBLB, and also from the improvement of PaO2 after the withdrawal of bucillamine. We treated the patient with prednisolone, and a favorable response was noted. A lymphocyte stimulation test using bucillamine was positive. A video-assisted thoracic surgery lung biopsy showed findings compatible with acute interstitial pneumonia without the association of hyaline membrane formation. A focal fibrosis was also observed. We believe that this is the only reported case of pathologically proven bucillamine-induced interstitial pneumonitis, in which a surgical lung biopsy was performed.
Anti-Inflammatory Agents, Non-Steroidal↗
Glucocorticoid induction of the glaucoma gene MYOC in human and monkey trabecular meshwork cells and tissues.
PURPOSE: To examine the intracellular and extracellular expression of myocilin in the human and primate trabecular meshwork (TM) in the presence and absence of glucocorticoids. METHODS: Myocilin expression was examined in cultured human TM cells by Northern blot analysis and myocilin antibody-mediated immunoprecipitation. Myocilin expression was quantified using high-resolution two-dimensional polyacrylamide gel electrophoresis of radiolabeled proteins from human TM cells, TM tissue explants, and perfused human anterior segments cultured with and without dexamethasone (DEX) for 14 to 21 days, as well as TM tissue from pigtailed monkeys treated orally for 1 year with cortisone acetate. Immunofluorescence with anti-myocilin antibodies was used to localize cellular and extracellular expression of myocilin in cultured human TM cells. RESULTS: Glucocorticoid treatment caused a significant induction of myocilin mRNA, a tetrad of cell-associated proteins, and 8 to 20 secreted proteins (molecular mass [M(r)] 56 and 59 kDa and isoelectric point [pI] 5.2 and 5.3) in some, but not all the cultured human TM cells and explanted tissues. Western immunoblot analysis using anti-myocilin peptide antibodies identified these proteins as encoded by the MYOC gene. There was significant induction of the myocilin proteins in three perfusion-cultured human eyes, in which DEX-induced elevated intraocular pressure developed. Monkeys treated 1 year with cortisol acetate showed steroid glaucoma-like morphologic changes in the TM that correlated with the induction of myocilin in the TM. Immunofluorescence analysis of cultured TM cells localized myocilin intracellularly in discrete perinuclear and cytoplasmic vesicular deposits as well as extracellularly on the cell surface associated with the extracellular matrix. In several DEX-treated TM cell lines, there were significant levels of myocilin secreted into the media. Enzymatic deglycosylation of proteins in the TM media converted the higher molecular weight isoforms of myocilin (approximately 57 kDa) to the lower molecular weight isoforms ( approximately 55 kDa). CONCLUSIONS: Although the function of myocilin is unknown, induction of these TM proteins was found in eyes in which glucocorticoid-induced ocular hypertension developed. Therefore, myocilin may play an important pathogenic role in ocular hypertension in addition to its role in certain forms of POAG.
Aged↗
[A case of pulmonary lymphangioleiomyomatosis in an elderly woman].
We encountered a postmenopausal woman in whom pulmonary lymphangioleiomyomatosis was pathologically diagnosed. Cases of pulmonary lymphangioleiomyomatosis are rare in postmenopausal women. The patient was the oldest in whom such a case was reported in the literature. Pulmonary lymphangioleiomyomatosis should be on the list of differential diagnoses for cases of pulmonary cystic lesions, even in postmenopausal women.
Aged↗
[Pathologic findings both before and after steroid therapy in a case of desquamative interstitial pneumonia].
A 62-year-old man was admitted to our hospital because of dyspnea on effort. Histological findings from video-assisted thoracoscopic surgical biopsy were desquamative interstitial pneumonia (DIP). Two months after the introduction of steroid therapy, the patient underwent right middle lobe lobectomy for primary lung cancer. The histologic findings in this lobe revealed non-specific interstitial pneumonia, not characteristic of DIP. This case was the first in which histologic examination revealed DIP both before and after steroid therapy.
Humans↗
[Band heterotopia in a male patient with Lennox-Gastaut syndrome].
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Adult↗
[Invasive pulmonary aspergillosis following influenza A infection].
A 55-year-old man with arc welder's pneumoconiosis who presented with bilateral pneumonia was admitted to our hospital. Streptococcus pneumoniae and Aspergillus fumigatus were cultured from sputum on admission. The patient was treated with antibiotics and an anti-fungal agent, but his chest radiograph shadows became exacerbated, and he died of respiratory failure on the fourth day of hospitalization. Histological examination of postmortem lung tissue revealed necrotizing aspergillous pneumonia. The results of hemagglutination inhibition tests for influenza A (H3 N2) were x16 in September 1999, and x512 on the third day of hospitalization. We diagnosed this patient's condition as invasive pulmonary aspergillosis associated with influenza A viral infection. The suppression of cellular immunity, lymphocytopenia, and destruction of airways-mucociliary transport induced by influenza A viral infection were suspected to have predisposed him to aspergillus superinfection.
Aspergillosis↗
Analysis of Cytoskeletal Proteins in Rat Selenium Cataract Using Two-dimensional Electrophoresis.
Background and Purpose: Previous studies used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to characterize the modifications to lens proteins during opacification in the selenite model for cataract. To analyze the protein modifications in more detail, two dimensional electrophoresis (2 DE), which is more sensitive than 1 D electrophoresis, was used.Results: The results of 2 DE demonstrated rapid changes in cytoskeletal proteins including spectrin and vimentin at the earliest stages of opacification.Conclusion: The results suggested that the mechanism of opacification might involve changes in cytoskeletal proteins during the earliest stages of cataract formation.
Journal Article↗
Analysis of Proteins During Recovery from Lens Opacity. Analysis of Selenite Cataract Model Using Sprague- Dawley and Wistar Rat.
Background and Purpose: The cataract in Sprague-Dawley rats injected with selenite is a dense nuclear opacity that appears by 4 or 5 days after selenite injection and becomes irreversible by 7 days. Injection of Wistar rats with selenite resulted in a similar nuclear opacity by 4 or 5 days that began to recover transparency by 7 days. In this report, the cytoplasmic proteins were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in lenses from Sprague-Dawley and Wistar rats at 4 and 7 days after injection.Results: In the opaque lens cells, degradation of the 31 kDa protein and cytoskeletal proteins (vimentin, spectrin, and actin) was observed during cataract development using SDS-PAGE and Western blot analysis. During recovery from opacity, the decreased 31 kDa protein and the vimentin increased.Conclusion: The results suggest that the 31 kDa protein and the vimentin may be important for recovery of transparency in a reversible model of cataract formation.
Journal Article↗
Ultrasensitive determination of phencyclidine in body fluids by surface ionization organic mass spectrometry.
Gas chromatography (GC)/surface ionization organic mass spectrometry (SIOMS) has been found to give much higher sensitivity for measurements of phencyclidine (PCP) than the conventional GC/electron impact (EI)-mass spectrometry (MS). Thus, we have established a detailed procedure for measurements of PCP in body fluids by both mass chromatography and selected-ion monitoring (SIM) of SIOMS using pethidine as an internal standard (IS). Good linearity was found in the range of 0.25-10 ng/mL of whole blood or urine, when measured by mass chromatography, and in the range of 0.025-1.0 ng/mL of whole blood by SIM. The recoveries of PCP and IS spiked to whole blood were 106 +/- 17% at 1 ng/mL and 113 +/- 11% at 5 ng/mL; that of IS was 97.8 +/- 10.4% at 5 ng/mL. The detection limits (signal-to-noise ratio = 3) were estimated to be 0.05 ng/mL of whole blood or urine by mass chromatography and 0.01 ng/mL of whole blood by SIM. The coefficients of intraday and interday variations were not greater than 10.3%. We could detect PCP from rat whole blood 2 h after subcutaneous injection of PCP (1 mg/kg) by mass chromatography. The mean PCP concentration in rat blood was 47.7 +/- 6.2 ng/mL (mean +/- SD, n = 4).
Animals↗
Determination of pentazocine in human whole blood and urine by gas chromatography/surface ionization organic mass spectrometry.
Pentazocine has been found to be measurable with much higher sensitivity by gas chromatography (GC)/surface ionization (SI) organic mass spectrometry (OMS) than by the conventional GC/electron ionization (EI) mass spectrometry. The compound was extracted from human whole blood and urine with Sep-Pak C(18) cartridges before analysis by GC/SIOMS; recoveries were > 96.6% for both samples. The calibration curves were linear in the range 6.25-100 ng ml(-1) and the detection limits were 500 pg ml(-1) of a sample by selected ion monitoring (SIM) with GC/SIOMS. The intra- and inter-day relative standard deviations for the determination of pentazocine in whole blood and urine were not greater than 9.6%. The sensitivity for pentazocine obtained by SI-SIM was about 60 times higher than that obtained by EI-SIM. To validate the present GC/SIOMS method for pentazocine, whole blood and urine samples collected from two volunteers 1-6 h after intramuscular injection of 15 mg of pentazocine were analyzed. The concentrations were 13.5-59.3 ng ml(-1) for whole blood and 0.39-4.00 microg ml(-1) for urine.
Analgesics, Opioid↗
Effect of alpha(1)-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil.
The pharmacokinetics of tamsulosin (TAM) was investigated using male Sprague-Dawley rats in which plasma alpha(1)-acid glycoprotein (alpha(1)-AGP) levels were elevated by the subcutaneous injection of 0.2 mL/kg of turpentine oil. alpha(1)-AGP levels increased about eight times after turpentine oil treatment, causing a threefold decrease in plasma unbound fraction (f(u)) of TAM. When 0.3 mg/kg of TAM was dosed intravenously, total and nonrenal clearances (CL(tot) and CL(nr)) in turpentine-treated rats were 47% and 44% lower than those in nontreated controls, respectively. The area under the concentration-time curve of plasma unbound TAM (AUC(inf,u)) was lower than that in the control. When 1 mg/kg of TAM was dosed orally, oral clearance (CL(oral)) in alpha1-AGP-induced rats was 65% lower than in the control. The AUC(inf,u) and unbound oral clearance (CL(oral,u)) were nearly equal in both groups. Moreover, a positive correlation was observed between fu and CL(oral) of TAM (r(2) = 0.603, P < 0.01), whereas no correlation was observed between f(u) and CL(oral,u). The absolute bioavailability (BA) increased from 19.2% to 46.9% by induction of alpha(1)-AGP. These results suggest that decreased f(u) caused by the elevation of plasma alpha(1)-AGP level affects the pharmacokinetics of TAM, but does not affect the CL(oral,u,) which represents the hepatic metabolism of TAM.
Animals↗