Numerical method for large-scale non-Hermitian matrices and its application to percolating Heisenberg antiferromagnets.
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Biomedical subjects
Publications and source records attributed to T Terao.
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The aggregation of bovine serum albumin (BSA) in the solid state and in solution was studied to elucidate the effect of water mobility on the aggregation rate and mechanism. The results suggest that the freeze-dried BSA forms covalently-bonded aggregates via disulphide bonding during storage in the moistened solid state and in solution. The aggregation rate largely depended on the water content. The freeze-dried BSA to which a small amount of water was added (in the moistened state) was found to be more liable to aggregation than that in solution. The aggregation rate in in the moistened solid state exhibited a maximum at a very low level of moisture. In contrast, the aggregation rate in solution increased with increasing ratio of water to protein (with decreasing protein concentration). The results suggest that the increased rate is related to the increase in water mobility, as measured by the spin-lattice relaxation time, T1, of water using 17O NMR, with increasing ratio of water to protein.
Urinary trypsin inhibitor-related substance (UTI-R) was measured in the amniotic fluid (n = 30), first neonatal urine (n = 10), meconium (n = 10), and adult urine (n = 10). The concentration of UTI-R excreted in the neonatal urine was significantly higher than in adult urine and meconium. Positive immunostaining for UTI was observed in amnion, umbilical cord and placenta. The effect of UTI was studied on the amnion using fura-2-acetoxymethyl ester. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-beta (TNF-beta) led to a significant increase in relative fluorescence release (RFR) of fura-2 (p < 0.05 and p < 0.02, respectively) while endotoxin did not show significant changes of RFR of fura-2. The effect of IL-1 beta and TNF-beta was almost abolished after incubation of UTI with the amnion cells (p < 0.03). This suggests that UTI may have a protective effect on the amnion especially against IL-1 beta and TNF-beta.
Two depressive patients with systemic lupus erythematosus (SLE) and cerebral infarction, while being treated with corticosteroid, are described. In both cases, lithium was remarkably effective and no severe side-effects occurred. These findings suggest that lithium can be a useful antidepressant agent in the treatment of depressive SLE patients.
Monoclonal anti-peptide antibodies against the extracellular domain of human growth hormone receptor (hGHR) were prepared. Four monoclonal antibodies (mAbs) reacted with an extracellular domain protein produced by genetic engineering. Among them, GHRP2-88 was the most reactive against hGHRs from human IM-9 cells. The lower limit of detection for immunoblotting using this mAb was about 200 pg hGHR. The GHRP2-88 antibody also reacted with deglycosylated hGHRs from tunicamycin-treated IM-9 cells and with the growth hormone-binding protein (GH-BP) in human plasma.
The stabilizing effect of mannitol during the freeze-drying of proteins was studied using L-lactate dehydrogenase (LDH, rabbit muscle), beta-galactosidase (Escherichia coli) and L-asparaginase (Erwinia chrysanthemi) as model proteins. Crystallization of mannitol was studied by powder X-ray diffraction and differential scanning calorimetry (DSC), in relation to the stabilizing effect. All the enzymes were protected concentration-dependently by amorphous mannitol, but the stabilizing effect was decreased with an increase in mannitol crystallinity. The heat-treatment of frozen solutions above crystallization temperature prior to drying enhanced mannitol crystallization and LDH inactivation. The importance of maintaining excipients in an amorphous state during freeze-drying, previously reported for Aspergillus oryzae beta-galactosidase (K. Izutsu et al., Pharm. Res., 10, 1233 (1993)), was confirmed using three different enzymes.
Urinary trypsin inhibitor is a glycoprotein which has an inhibitory effect on many enzymes, especially neutrophil elastase. The concentration of urinary trypsin inhibitor in serum (maternal and fetal), urine and amniotic fluid was measured in 20 cases of preeclampsia and compared with levels in normal pregnancy. Urinary trypsin inhibitor levels were significantly increased in the maternal and fetal serum of preeclamptic patients compared to normal pregnancy (p < 0.0001), as well as in urine and amniotic fluid of the same patients. Relative fluorescence release of a calcium chelating agent (fura-2) from human umbilical vein endothelial cell cultures was significantly increased by preeclamptic serum compared to serum of normal pregnant women (p < 0.03). After incubation of urinary trypsin inhibitor with the cultures, significant decrease of fura-2 release was observed (p < 0.03). Urinary trypsin inhibitor has an effect on suppression of activated neutrophils, elastase production and may have a protective effect on endothelial cells.
In 23 male patients, the electrical activity of external urethral sphincter muscle was sampled before examination of cystometry (Rest), at first desire to void (FDV), maximum desire to void (MDV) and during urination (Void) by means of electromyography (EMG). Sampling time of each event was 2400 msec. The electrical activity was amplified with a lower limiting frequency of 20 Hz and an upper limiting frequency of 10000 Hz, and recorded on magneto-optical desk. Spectra were obtained using a Hamming window. The action potential of the muscle was quantitatively analyzed and power spectrum of the needle EMGs were analyzed from the magneto-optical disk by a spectrum analyzer using fast Fourier transformation (FFT, Sande-Tukey method). From each power spectrum, mean power frequency (MPF) was obtained from a calculator connected to the spectrum analyzer. Twenty three patients were divided into three groups as follows: 8 patients without any neurological abnormality (normal group), 7 patients with neurogenic bladder showing detrusor-sphincter-dyssynergia (DSD+ group) and 8 patients with neurogenic bladder without detrusor-sphincter-dyssynergia (DSD- group). The results obtained were as follows: 1) The motor unit potentials at Rest had the mean amplitude of 210 +/- 59.4 microV, 329.3 +/- 157.1 microV and 177.6 +/- 132.8 microV in normal group, DSD+ group and DSD- group, respectively. The mean duration were 4.3 +/- 0.2 msec, 5.9 +/- 1.9 msec, and 7.3 +/- 4.5 msec., respectively. The mean phases were 2.8 +/- 0.6, 2.8 +/- 0.5 and 2.5 +/- 0.3, respectively. Statistically there was no difference in amplitude, duration and phase among three groups. 2) In normal group, the power over than -20 dB was distributed from 150 to 220 Hz windows at Rest and FDV. The needle EMGs at MDV showed interference pattern and the power increased over -20 dB in all windows. The power of high frequency area relatively increased. The action potential of the muscle disappeared during urination and the power also disappeared. The average MPF was 103 Hz, 102 Hz, 150 Hz and 98 Hz at Rest, FDV, MDV and Void, respectively. 3) In DSD+ group, the needle EMGs showed interference pattern in MDV and Void, and the power increased only in low frequency area. The average MPF was 104 Hz, 105 Hz, 114 Hz and 120 Hz at Rest, FDV, MDV and Void, respectively. 4) Because of damage to nerves, the action potential of the muscle was difficult to obtain from 3 patients of DSD- group, and the power was not demonstrated.(ABSTRACT TRUNCATED AT 400 WORDS)
We studied the optimal time of carbohydrate ingestion required to restore muscle glycogen storage after exhaustive exercise in rats. The animals were divided into 4 groups (IN0, IN30, IN60 and IN120), each receiving 30% glucose solution (30 g/kg body weight) through a stomach tube 0, 30, 60 or 120 minutes after exercise. Six hours after administration of glucose, the glycogen concentration in the m. extensor digitorum longus returned to the baseline in the IN0 group, while reaching only 77%, 80% and 73% of the baseline in the IN30, IN60 and IN120 groups, respectively. There was a significant difference in this variable between the IN0 group and any of the three other groups. On the other hand, the glycogen concentration in the m. soleus returned to the baseline in all groups with no difference. These findings suggest that muscle glycogen may be most efficiently resynthesized if carbohydrate is given immediately after exercise, and that muscle glycogen resynthesis may vary with the type of muscle.
A 71-year-old woman was admitted with the chief complaint of headache, lumbago and slight fever. Computerized tomographic (CT) scan demonstrated a large soft tissue mass with multiple cystic necrosis in the right adrenal region. The plasma norepinephrine concentration was excessive and serum levels of neuron-specific enolase (NSE), calcitonin and parathormone were elevated. MIBG scintigraphy showed a high uptake in the same region. Under the diagnosis of pheochromocytoma without distant metastasis, right adrenalectomy was performed. The tumor was removed en bloc with right kidney and a part of the liver because of inflammatory adhesion. The histological examination revealed benign pheochromocytoma. After the operation, norepinephrine and calcitonin decreased to normal but the levels of NSE and PTH remained high. One year after operation, chest X-ray revealed multiple lung metastases and after 1.5 years she died of respiratory failure. Autopsy revealed multiple lung and bone metastases and a liver metastasis, parathyroid glands showed hyperplasia but the thyroid gland showed no abnormal change. This clinical course suggests that serum NSE might be a useful tumor marker for differentiating malignant pheochromocytoma from benign one, and this tumor producing calcitonin caused secondary hyperparathyroidism.
A selective inhibitory antibody, raised against human high molecular weight urokinase-type plasminogen activator (HMW-uPA), was examined to determine whether it would inhibit production of experimental and spontaneous lung metastasis by murine Lewis lung carcinoma (3LL) cells. Polyclonal antibody to human uPA cross-reacts with the murine uPA and inhibits murine uPA activity. When examined with an in vitro assay system using a modified Boyden chamber, the anti-catalytic IgG to uPA suppressed the invasion of tumor cells through Matrigel. Anti-uPA IgG inhibited neither the cell proliferation nor the binding of tumor cells to Matrigel, and showed no significant suppression of chemotactic migration of tumor cells to fibronectin. In an in vivo spontaneous metastasis assay, multiple subcutaneous (s.c.) injections of anti-uPA IgG (up to a concentration of 200 micrograms [= 500 inhibitory unit/mouse/day] for 7 days immediately after s. c. tumor cell inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dose-dependent manner. The inhibition of lung metastasis was not due to direct antitumor effects of anti-uPA IgG. In an in vivo experimental metastasis assay, multiple s. c. injections of anti-uPA IgG for 7 days after intravenous (i. v.) tumor cell inoculation did not reduce the number of lung tumor colonies. These results suggest that uPA more efficiently regulates the mechanism involved in the entry into vascular circulation of tumor cells (intravasation) than in extravasation, during the metastatic process.
The present study was undertaken to assess the role of tumor infiltrating lymphocytes and polymorphonuclear leukocyte-derived human leukocyte elastase (HLE) as an inactivator of urokinase-type plasminogen activator (uPA) activity. We have investigated the localization of pro-uPA/uPA and HLE immunohistochemically and quantitated in paraffin-embedded formalin-fixed uterine cervical cancer tissue sections (stage II) in 13 patients with positive lymph-nodes metastasis and in 16 cases with node-negative. The invasively growing and metastasizing tumor cells consistently contained uPA enzyme activity. When investigated immunohistochemically with antibody to uPA, different parts of individual tumors showed a pronounced heterogeneity in staining intensity. Strong staining was found in the areas with invasive growth and degradation of surrounding normal tissue. A statistically significant higher node-positive rate was observed in patients having tumors with strong uPA stainings than in those with weak stainings. On the other hand, inflammatory cells such as polymorphonuclear cells were located in aggregates or diffusely spread within tumor stromal tissue. The inflammatory reaction seemed to be most intense at the border between the surrounding normal stromas and the tumor tissue. These cells produced and secreted HLE. A statistically significant higher node-positive rate was observed in patients having tumors with weak HLE stainings than in those with strong stainings. Thus, uPA and HLE staining intensities in tissue specimens appear to be independent predictors of increasing and decreasing risk for node-positive, respectively, suggesting that HLE may act as a defence against tumor cell invasion and metastasis.
It has been widely accepted that the estrogen is one of the contributing factors to the development of endometrial cancer of the uterus. The objective responsiveness of recurrent endometrial cancer to medroxyprogesterone acetate (MPA) has been substantiated. Many researchers have examined whether the anti-estrogenic agents could be the choice of treatment of endometrial cancer including tamoxifen (TAM), aromatase inhibitors, danazol and luteinizing releasing hormone (LHRH)-agonist as an adjunctive endocrine therapy. In this review, we discussed the pharmacological and clinical aspects of these new agents.
BACKGROUND: Acute fatty liver of pregnancy, the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP), and severe preeclampsia form a disease spectrum. We report a case that showed a vasospastic phenomenon supported angiographically and hematologically. CASE: A 31-year-old Japanese woman presented at 37 weeks gestation with a 1-week history of nausea, vomiting and general fatigue. She underwent cesarean delivery for fetal distress. Liver dysfunction and disseminated intravascular coagulopathy were detected. The celiac angiogram showed vascular narrowing and irregularity of the vascular wall. Serum endothelin and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha were increased at the same time. The patient experienced rapid resolution of symptoms and laboratory abnormalities in the immediate postoperative period. CONCLUSION: A pregnancy complicated by liver dysfunction showed a vasospastic phenomenon, which may suggest the presence of a vasospastic syndrome.
This study was designed to elucidate the participation of endothelin-1(ET-1) in vivo and in vitro coagulation. The microvascular hemodynamic changes in terms of intravascular thrombus formation in rat mesentery induced by the superfusion of ET-1 (0.5, 1 and 2 pmol) were visualized by an intravital microscope system assisted by television-video tape recorder system. In addition to vasoconstriction we observed the blockade of circulation by clumps resembling thrombus in a dose dependent fashion by ET-1. Thrombus formation could be attenuated by pretreatment with superfusion of 3.8% Na citrate solution but not by the prior superfusion of 1 to 3 ng of nitroglycerine. Thrombus formation was found after the administration of 10 microliters of CaCl2 (100 nM) solution in Na citrate (3.8%, 20 microliters) and ET-1 treated field. In vitro study, a dose dependent increase in TAT (thrombin-antithrombin complexes) and decrease in AT III (antithrombin III) (%) activity, the prolongation of PT (prothrombin time) and APTT (activated partial thromboplastin time) was found by administering ET-1 immediately in native (unanticoagulated) blood in silicon coated test tubes (p < 0.05; n = 6). However in citrated blood, TAT complexes, AT III (%) activity, PT and APTT were not significantly changed after administration of the same doses of ET-1 (p > 0.05; n = 6). Therefore, this study suggested that endothelin-1 caused intravascular thrombosis and enhanced intra test tube coagulation which could be attenuated by blocking ionic calcium.
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The present study was undertaken to assess the role of membrane-associated cathepsin B as an activator of receptor-bound single-chain urokinase-type plasminogen activator (pro-uPA) and to determine the importance of receptor-bound uPA activity in the destruction of extracellular matrix by tumor cells with subsequent invasion through basement membranes. Ovarian cancer HOC-I cells express pro-uPA/HMW-uPA and cathepsin B on their surface. uPAs are bound to a specific surface receptor, about 30% of which is saturated. 60% of the receptor-bound uPA is pro-uPA. No reduction in the specific binding of biotinylated DFP-HMW-uPA was observed when cells were cultivated in the presence of E-64, a cysteine proteinase inhibitor, for 24 h. Inhibition of cell-surface cathepsin B activity was associated with a decrease in cell-bound uPA activity to undetectable levels, and > 95% of the membrane-associated uPA was pro-uPA in cells cultivated with E-64. This suggested that receptor-bound pro-uPA cannot be converted to HMW-uPA in the absence of enzymatically-active cathepsin B. The significance of the expression of cell-surface uPA activity regarding invasive potential was examined in an in-vitro Matrigel invasion assay. Decreased cell-surface uPA activity was associated with a decrease in invasive potential. These data support our hypothesis that membrane-associated cathepsin B may be important for the conversion of pro-uPA to HMW-uPA and that receptor-bound uPA activity constitutes an efficient mechanism which contributes to tumor cell invasion. As HOC-I cells produce both uPA and cathepsin B, the implications of tumor-cell-derived pro-uPA activation by cellular proteinase cathepsin B should be considered.
We have established an in vitro system for the culture of epithelial cells (ECs) from human uterine endometrium to examine the production of CA 125 and to characterize the CA-125 antigen purified from the conditioned media. CA-125 secretion was higher in heterotopic ECs than in eutopic ECs and it was more significant after heterotopic ECs reached confluence than during the logarithmic growth phase. CA-125 expression was observed mainly in the G0/G1-phase. CA-125 expression on cell membranes did not correlate with the volume of CA 125 released per cell, and there was no amplification of CA-125 expression in heterotopic EC membranes. Treatment of the purified CA-125 antigen with 6 M urea yielded a much lower molecular-mass peak (200 kDa). The results of Western blot indicated the presence of a single polydisperse band of 200 kDa in the conditioned media from eutopic ECs, whereas 2 major CA-125 isoforms of 200 kDa and 110 kDa, as well as 2 minor forms of 100 kDa and 70 kDa, were observed in the conditioned media of the heterotopic ECs. We conclude that, in heterotopic ECs, the 110-kDa CA-125 is more prominent than the 200-kDa antigen, and that the elevation of CA-125 levels in the conditioned media could be attributed to significantly increased release of 110-kDa CA-125 from heterotopic ECs.