Effect of protein kinase inhibitors on the superoxide generation and tyrosyl phosphorylation of prolylproline-primed human neutrophils.
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Dipeptides↗
Biomedical subjects
Y Sagara
Publications and source records attributed to Y Sagara.
Effect of estrogen on the size of low-density lipoprotein particles in postmenopausal women.
OBJECTIVE: To investigate the effects of estrogen on the size o low-density lipoprotein (LDL) particles in postmenopausal women. METHODS: We treated 20 postmenopausal women with 0.625 mg of conjugated equine estrogen daily for 3 months and measured the plasma levels of total cholesterol, triglyceride, high-density lipoprotein (HDL), and apolipoproteins A-I, A-II, and B before and after therapy. We also analyzed concentrations of LDL cholesterol and LDL apolipoprotein B. The diameter of LDL particles was determined by gradient gel electrophoresis. RESULTS: Estrogen caused significant decreases in the plasma levels of total cholesterol and apolipoprotein B and significant increases in the plasma levels of triglyceride, HDL cholesterol, and apolipoprotein A-I and A-II. Mean levels of LDL cholesterol and LDL apolipoprotein B were reduced significantly (by 16.31%, P < .001, and 16.91%, P < .001, respectively) after estrogen treatment. Estrogen also significantly reduced the size of LDL particles, from 25.74 +/- 0.66 (mean +/- standard deviation) to 24.95 +/- 0.78 nm (P < .001). The LDL particle diameter correlated negatively with the plasma level of triglyceride (pre-treatment: r = 0.87, P < .001; post-treatment: r = 0.88, P < .001). Estrogen significantly increased the prevalence of LDL subclass pattern B, from 30 to 65% (P < .03). CONCLUSION: Estrogen affects lipid metabolism favorably by reducing the plasma concentration of LDL particles. Estrogen-induced increase in the plasma level of triglyceride appears to reduce the size of LDL particles.
Apolipoproteins↗
Effectiveness of mammographic screening for breast cancer in women aged over 50 years in Japan.
The optimal age for effective screening of subjects for breast cancer by mammography in Japan was studied based on the results of two mammographic screening systems (systems I and II) in Tokushima Prefecture. System I consisted of visit screening using a bus equipped with a mammographic apparatus. System II consisted of central screening performed at Tokushima Health Screening Center. The examinees numbered 2,500 and 3,707 in systems I and II, respectively. There was a significant difference between the two screening systems in the age distribution of the examinees. The detection rates of breast cancer were 0.6% and 0.24% in systems I and II, respectively, which are 2-5 times higher than that (0.12%) obtained by conventional screening using physical examination alone. The detection rate increased especially in the sixth and seventh decades of life. The sensitivity of mammography screening was 93.3% in system I and 81.1% in system II. Higher sensitivity (100%) than that (73%) of screening by physical examination was obtained in women aged over 50. The proportion of stage I was 60% in system I and 66.7% in system II, compared with 32-65% in the United States and Europe. The rates of no nodal involvement were high, being 77.8% and 83.3% in systems I and II, respectively, compared with 57-71% in other countries. Breast-conserving therapy was applied to 18 of the 24 patients with breast cancer detected by the two screening systems. In addition, in Wolfe's classification of mammograms, the proportion of DY (mammary dysplasia) pattern was remarkably low, being 3.2% in the sixth decade and 0.8% in the seventh decade, compared with 16.6% in women aged 49 years. These results indicate that mammographic screening is effective in women aged over 50 years in Japan, as has been found in other countries.
Aged↗
Nocturnal changes in pineal melatonin synthesis during puberty: relation to estrogen and progesterone levels in female rats.
Our objective was to evaluate the changes in melatonin synthesis during the peripubertal period in the female rat and to determine the effects of ovarian steroid hormones on melatonin synthesis. Pineal levels of tryptophan, 5-hydroxytryptamine (5-HT), melatonin and norepinephrine were determined in female Sprague Dawley rats (between 2 and 12 weeks of age) in the mid-dark during the daily light/dark cycle. Melatonin levels increased with age, parallel to pineal growth, until 6 weeks of age, when the vaginal opening was found in 66.7% of rats, and significantly decreased until 8 weeks of age, when the vaginal opening was found in all rats. Norepinephrine began to increase earlier and reached a mature level at 4 weeks of age. Treatments with bilateral ovariectomy at 4, 6, and 8 weeks of age resulted in significant increases in melatonin and 5-HT levels, and significant decrease in tryptophan level at 2 weeks after ovariectomy. Treatments with ovariectomy at 6 weeks of age produced a consistent increase in 5-HT level and a consistent decrease in tryptophan level until 6 weeks after ovariectomy. However, melatonin levels increased until 2 weeks after ovariectomy, then decreased and reached a control level at 6 weeks after ovariectomy. Subcutaneous implantation of estradiol-17 beta capsule and daily subcutaneous injection of estradiol benzoate (E2B) (1.0 microgram, 20 micrograms) for two weeks in the rats ovariectomized at 4, 6, and 8 weeks of age resulted in significant decreases in melatonin and 5-HT levels and a significant increase in tryptophan level at 2 weeks after ovariectomy. A smaller dose of E2B (0.1 microgram) produced the same effects in the rats ovariectomized at 4, but not at 6 and 8 weeks of age. Administration of progesterone (200 micrograms/day) for 2 weeks did not produce any significant changes in melatonin, 5-HT, and tryptophan levels. Norepinephrine levels were not changed by any of the above treatments. These results suggest that estrogen, but not progesterone, can modulate nocturnal pineal melatonin synthesis in peripubertal female rats, and that the decline in the melatonin synthetic activity during the pubertal period might be related to the increasing levels of endogenous estrogen, which is secreted from the maturing ovary. The sites of action of the inhibitory effect of estrogen on the pineal melatonin synthesis may be multiple.
Age Factors↗
Melatonin inhibits vasospastic action of hydrogen peroxide in human umbilical artery.
We evaluated the antioxidant property of melatonin as it relates to the vasospastic effect of hydrogen peroxide (H2O2) on the human umbilical artery. Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between weeks 37 and 39 of gestation. Changes in maximal potassium chloride (KCl)-induced tension were measured in arterial segments with intact endothelium. Segments were treated with H2O2 alone, or were pretreated either with an H2O2 scavenger (catalase, 2000 i.u.), a hydroxyl radical scavenger (mannitol, 10(-2) M), a nitric oxide-synthesis inhibitor (L-NG-monomethyl arginine, LNMA, 2 x 10(-4) M), or melatonin (10(-6) M to 10(-4) M). The effect of H2O2 (10(-4) M) on the relaxation induced by the calcium ionophore A23187 was also determined in arterial segments, with or without pretreatment with melatonin (10(-6) M, 10(-4) M). H2O2 (10(-6) M to 10(-4) M) potentiated vascular tension in a concentration-dependent manner (P < 0.0001). Pretreatment with LNMA significantly suppressed the vasospastic effect of H2O2 (P < 0.0001). Pretreatment with either catalase or mannitol significantly reduced the vasospastic effect of H2O2 (P < 0.005, P < 0.002, respectively). Melatonin also significantly reduced the vasospastic effect of H2O2 in a concentration-dependent manner (H2O2 10(-6) M, P < 0.0001 : H2O2 10(-5) M, P < 0.0001 : H2O2 10(-4) M, P < 0.00001). Pretreatment with H2O2 significantly inhibited the relaxation induced by the calcium ionophore A23187 (P < 0.005). Treatment with melatonin prior to exposure to H2O2 significantly restored the relaxation induced by A23187 (P < 0.005). Results suggest that H2O2 potentiates vascular tension in the human umbilical artery, perhaps by suppressing the endothelial synthesis of nitric oxide. Melatonin significantly suppressed the vasospastic effect of H2O2, possibly due to its ability to scavenge the hydroxyl radical.
Antioxidants↗
Melatonin suppresses vasospastic effect of hydrogen peroxide in human umbilical artery: relation to calcium influx.
We evaluated the hydroxyl radical scavenging effect of melatonin on the vasospastic action induced by hydrogen peroxide in human umbilical artery. Helical sections were made of umbilical arteries obtained from healthy pregnant women who were delivered between 37 and 39 weeks of gestation. Changes in maximal potassium chloride (KCl, 10[-2] M)-induced tension were measured in umbilical artery segments with intact endothelium. Segments were treated with H(2)O(2) (10[-9] M to 10[-7] M) only, or were pretreated with an H(2)O(2) scavenger (catalase, 2,000 IU), a hydroxyl radical scavenger (mannitol, 10[-2] M), or melatonin (10[-8] M to 10[-6] M). The effect of H(2)O(2) on the response of the segments of umbilical artery to external calcium was determined. Changes in KCl-induced contraction were also determined in segments pretreated with an inhibition of intracellular calcium release (ryanodine, 10[-4] M) prior to exposure to H(2)O(2). Pretreating the segments of umbilical arteries with H(2)O(2) (10[-8] M, 10[-7] M) significantly potentiated the maximal contraction induced by KCl (P < 0.0001, P < 0.03, respectively). Pretreatment with either catalase or mannitol significantly reduced the vasospastic effect of H(2)O(2) (10[-8] M) (P < 0.0001, P < 0.0001, respectively). Melatonin also significantly reduced the vasospastic effect of H(2)O(2) (10[-8] M), in a concentration-dependent manner (P < 0.0001). H(2)O(2) (10[-8] M) significantly increased the contractile response to external calcium. Melatonin pretreatment significantly suppressed the contractile response to external calcium. Treatment with ryanodine prior to exposure to H(2)O(2) did not affect KCl-induced contraction. Results suggest that H(2)O(2) potentiates the KCl-induced maximal contraction of the human umbilical artery, perhaps by increasing calcium influx via activation of the voltage-dependent calcium channel. Melatonin significantly suppresses the vasospastic effect of H(2)O(2), probably due to its scavenging of the hydroxyl radical.
Adult↗
Trypsin-sensitive and -resistant components in human T-cell membranes required for syncytium formation by human T-cell lymphotropic virus type 1-bearing cells.
Human T-cell lymphotropic virus type 1 (HTLV-1) envelope proteins play an important role in viral entry into target cells. In a syncytium formation assay consisting of a coculture of HTLV-1-bearing cells and target cells, mature gp46 and gp21 proteins each inhibited syncytium formation induced by HTLV-1-bearing cells. Experiments with 125I-labeled proteins showed that 125I-gp46 bound specifically with MOLT-4 target cells even in the presence of large amounts of gp21, whereas 125I-gp21 binding to target cells was completely blocked in the presence of large amounts of gp46. These observations suggest that HTLV-1 envelope proteins in syncytium formation interact with at least two components, which are located close to each other on the cell membrane. We isolated two components from MOLT-4 cell lysate, using Sepharose 4B columns coupled with peptides corresponding to amino acids 197 to 216 and 400 to 429, respectively, of the envelope protein. One is a trypsin digestion-sensitive component of approximately 34 to 35 kDa, which interacts specifically with gp46. The other is a nonprotein component, which interacts with gp21. This component was destroyed by sodium periodate oxidation and was partitioned into the methanol-chloroform phase. These observations suggest that these two components play an important role in HTLV-1 entry into target cells via membrane fusion.
Cell Membrane↗
Clinical usefulness of urinary CrossLaps as a sensitive marker of bone metabolism.
CrossLaps peptide [Glu-Lys-Ala-His-Asp-Gly-Gly-Arg], a part of the C-telopeptide of the alpha 1-chain of type I collagen of bone, is a recently developed biochemical marker of bone turnover. In this study, the clinical utility of measurement of urinary CrossLaps was investigated in eleven premenopausal women who received a gonadotropin-releasing hormone (GnRH) agonist for 6 months for treatment of adenomyosis (n = 1) or leiomyomas (n = 10). Along with urinary CrossLaps, the levels of various biochemical markers, and serum estradiol, calcitonin and intact parathyroid hormone (i-PTH) were measured, and lumbar spine bone mineral density (BMD) was also monitored before, during, and at the end of the course of GnRH agonist therapy. Apart from CrossLaps, markers of bone resorption tested were urinary pyridinoline, deoxypyridinoline and hydroxyproline. Markers of bone formation tested were serum osteocalcin and bone-specific alkaline phosphatase (B-ALP). Serum estradiol levels decreased to undetectable levels at 2 months of GnRH agonist therapy. The values for all biochemical markers increased significantly throughout the therapy. The degree of an increase in CrossLaps levels was greater than that in all other markers. Mean lumbar spine (L2-L4) BMD was decreased by 7.2% at 6 months of treatment. The percent change in BMD at 6 months of treatment correlated inversely with the percent change in CrossLaps levels from the baseline to 1, 2, and 5 months of treatment. These results indicate that measurement of urinary CrossLaps might be a useful tool to predict the risk of bone loss caused by hypoestrogenism including GnRH agonist therapy.
Adenomyoma↗
Effect of nitric oxide, prostacyclin, and thromboxane on the vasospastic action of hydrogen peroxide on human umbilical artery.
BACKGROUND: The effect of hydrogen peroxide (H2O2) on vascular tone in the human umbilical artery was investigated to determine the mechanism of vasospasm in preeclampsia. METHODS: Helical sections of the umbilical artery were obtained from healthy pregnant women who delivered between the 37th and 39th week of gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (PG F2 alpha) were measured (isometric mechanical activity). Segments were treated with H2O2 alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals (mannitol), an inhibitor of thromboxane synthesis (sodium ozagrel), and an inhibitor of nitric oxide synthesis (L-NG-monomethyl arginine, LNMA), or an inhibitor of prostacyclin synthesis (tranylcypromine, TCP). RESULTS: Vascular tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H2O2. Removal of the endothelium decreased the vascular tension induced by H2O2. Treatment with TCP and LNMA potentiated the vascular tension. Pretreatment with TCP and LNMA reduced the vasospastic action of H2O2, whereas pretreatment with sodium ozagrel did not. CONCLUSION: Vascular tension in human umbilical arteries was potentiated by H2O2, and may be mediated by a suppression of the activity of nitric oxide or of prostacyclin. A direct action of H2O2 on vascular smooth muscle may also be involved.
Epoprostenol↗
Vasospastic action of hydrogen peroxide in human umbilical artery: relation to protein kinase C and calcium influx.
BACKGROUND: We have demonstrated that hydrogen peroxide (H2O2) potentiated vascular tension in human umbilical artery, perhaps by suppressing the synthesis of nitric oxide and prostacyclin. This study was conducted to evaluate whether the activation of protein kinase C (PKC) or voltage-dependent calcium channel mediated the vasospastic effect of H2O2. METHODS: Helical sections of the umbilical artery were obtained from healthy pregnant women who delivered between 37th and 39th week of gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (9 x 10(-7) M) were measured (isometric mechanical activity). Segments were treated with H2O2 (10(-6)-10(-4) M) alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals (mannitol, 10(-2) M), an inhibitor of PKC (H-7, 6 x 10(-7) M). Effect of an activator of PKC (12-tetradecanoyl phorbol-13 acetate, TPA, 10(-6) M) on PG F2 alpha-induced tension was determined. Effects of H2O2 (10(-5) M) on the response of umbilical artery segments to an external calcium (10(-6)-10(-3) M) were determined. RESULTS: Vascular tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H2O2. Pretreatment with H-7 did not alter the response to H2O2. TPA did not produce a significant change in PG F2 alpha-induced tension. Pretreatment with H2O2 (10(-5) M) did not alter the contractile response to external calcium. CONCLUSION: H2O2 potentiated vascular tension in human umbilical arteries, a process that is independent of PKC and the voltage-dependent calcium channel. The vasospastic effect of H2O2 may be mediated by a suppression of the activity of nitric oxide and prostacyclin.
Analysis of Variance↗
[Surgical treatment for patients with atypical mycobacteriosis].
We have been conducting surgical therapy for patients with atypical pulmonary mycobacteriosis (AM) since 1965 and have reported on the outcome of this approach to treatment. We have found that chemotherapy is not adequately efficacious against type III Mycobacterium avium complex (MAC), which suggests that surgical intervention may be the optimum approach for MAC. Among MAC patients who were treated surgically at our hospital in the period between 1966 and 1994, 74 cases on whom postoperative follow-up observation was possible served as the subjects of the present investigation. We report here on the outcome of treatment and related problems in these patients. Thirty-nine patients gave positive results for bacterial discharge on smear tests and all were positive on culture. Operation was performed on the right lung in 46 patients and on the left lung in 16. Pneumonectomy was conducted in 10 patients and lobectomy in 20. Other operative modes used included segmental resection in 9, pyothorax in 7, and thoracoplasty in 5 patients. Postoperative bacterial excretion was observed in 15 patients and was persistent bacterial discharge were advanced cases with lesions in another lobe, cases with a past history of tuberculosis, cases of cavitation with lesions on the contralateral side or cases with massive bacterial discharge prior to surgery. Postoperative death occurred in 5 patients: the cause of death was lung cancer in 1 case, serum hepatitis in 1 case, and respiratory failure evidenced by enlarged shadows in 3 cases. These findings pointed to a marked significance of surgical therapy for MAC patients. However, recurrent bacterial discharge has been observed occasionally in some patients even 5 years after surgery. This suggests the need for careful ongoing assessment of the efficacy of surgical therapy and long-term postoperative follow-up.
Adult↗
[Lung volume reduction surgery for pulmonary emphysema--report of two cases].
Lung volume reduction surgery (LVR) was practiced in 2 male patients with pulmonary emphysema to improve pulmonary function. On admission, they complained of exertional dyspnea (Grade III of the Hugh-Jones dyspnea scale). Computed tomographic scan (band display) revealed emphysematous changes throughout both lung fields, especially in bilateral upper lobes. Nuclear lung perfusion scintigraphy showed markedly diminished blood flow in both upper lobes. The bilateral upper lobes of each patient were excised through median sternotomy using the linear stapling device. The staple lines were buttressed with bioabsorbable polyglycolic acid fabric. At 1 month after LVR, the forced expiratory volume in 1 second improved, respectively, from 0.51 L to 1.27 L (Case 1) and from 0.68 L to 0.85 L (case 2). In conclusion, LVR was useful to improve pulmonary function of the patients with pulmonary emphysema.
Aged↗
[Evaluation of thoracoscopic laser treatment and volume reduction surgery of diffuse pulmonary emphysema].
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Aged↗
Cooperative regulation of the human aromatase cytochrome P450 gene transcription by placenta-specific cis-acting elements.
Aromatase cytochrome P450 catalyses the reaction to convert androgens to estrogens by coupling with NADPH-cytochrome P450 reductase in the endoplasmic reticulum. The human aromatase cytochrome P450 gene (CYP19) is expressed in a variety of tissues under regulation of tissue-specific promoters. Previously, we localized a cell-type specific transcriptional enhancer element between -242 and -166 relative to the major cap site of the gene, by transient expression analysis in human BeWo choriocarcinoma cells. In the present study, we demonstrate that the enhancer element consists of two subelements, element I (located between -238 and -200), and element II (located between -196 and -176) as analysed by DNase I footprinting using the nuclear extracts of BeWo cells. The gel mobility shift assay shows that each of these subelements binds specific nuclear factor(s). The transient expression of the bacterial chloramphenicol acetyltransferase gene constructs involving the subelements in BeWo cells reveals that the elements activate reporter gene expression synergistically when present together, nevertheless each of the elements by itself also has an enhancer activity. The transient expression analysis further shows that element I is responsible for the transcriptional synergism with the binding site of a nuclear factor-interleukin-6 (NF-IL-6) (also known as CCAAT enhancer/binding protein beta), which is located between -2141 and -2115 relative to the major cap site of the gene. These results suggest that the enhancer element plays important roles in sustaining the high levels of CYP19 expression in placental cells in cooperation with other cis-acting transcritional regulatory elements.
Aromatase↗
[Mycetoma-forming pulmonary nocardiosis and endobronchial polypoid lesion].
A 46-year-old man was admitted to the hospital for evaluation of a dense infiltrative shadow in the right middle lung field. Bronchoscopic examination revealed a polypoid lesion in the right middle-lobe bronchus (Bb11(5)). Examination of a biopsy specimen showed a lump with many Nocardia asteroides bacteria. The response to chemotherapy, which included sulfomethoxazole, was poor, and therefore a right middle lobectomy was done. Three mycetomas were found inside the ectatic bronchi in the S5 area. Pulmonary Nocardia mycetoma is rare.
Bronchi↗
Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine induce the tyrosyl phosphorylation of 45 kDa protein in parallel with its stimulation of superoxide generation in human neutrophils.
Human peripheral blood polymorphonuclear leukocytes were preincubated with lanthionine, S-(2-aminoethyl)-L-cysteine, and some of their derivatives found in normal human urine and bovine brain. Among these compounds, lanthionine ketimine and to a lesser extent S-(2-aminoethyl)- L-cysteine ketimine enhanced the N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation. These ketimines induced tyrosyl phosphorylation of 45 kDa protein of cells. The tyrosyl phosphorylation was markedly increased with time, and the phosphorylation process was dependent on the concentration of both ketimines. However, lanthionine, 1,4-thiomorpholine-3,5-dicarboxylic acid, S-(2-aminoethyl)-L-cysteine and 1,4-thiomorpholine-3-carboxylic acid were without effect both on superoxide generation and on tyrosyl phosphorylation of 45 kDa protein. Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine also enhanced superoxide generation induced by opsonized zymosan but not the one induced by arachidonic acid and phorbol 12-myristate 13-acetate. Ketimine-primed superoxide generation and tyrosyl phoshorylation of 45 kDa protein were inhibited by genistein, an inhibitor of protein tyrosine kinase, but not by 1-(5-isoquinoline sulfonyl)-2- methylpiperazine, an inhibitor of protein kinase C.
Amino Acids, Sulfur↗
Prenatal monitoring in a family at high risk for ornithine transcarbamylase (OTC) deficiency: a new mutation of an A-to-C transversion in position +4 of intron 1 of the OTC gene that is likely to abolish enzyme activity.
DNA analysis of a male propositus with ornithine transcarbamylase (OTC) deficiency documented an A-to-C substitution in position +4 of intron 1. No other abnormalities were observed in the OTC gene, or at 563 bp upstream of the 5' site, which included a promoter region, or at 383 bp downstream of the termination codon, which included a polyadenylation signal sequence. This mutation produces an RsaI site in the sequence, which was used for prenatal monitoring in the fourth and fifth pregnancies. DNA from amniotic cells in the former case were positive for RsaI digestion and the SRY gene (sex determinant region Y), indicating hemizygosity for the mutant allele. OTC activity was not measurable, and mRNA of the OTC gene was not detected by Northern blotting in the affected fetal liver. RT-PCR (reverse transcription-PCR) demonstrated only the wild-type allele. Thus, the mutation interferes with RNA processing, and an extremely low amount of normally spliced mRNA for the OTC gene seems to have caused the disease in our patient. The fetus of the fifth pregnancy was a normal male, as confirmed postnatally.
Amino Acid Metabolism, Inborn Errors↗
Effect of cystathionine and cystathionine metabolites on the phosphorylation of tyrosine residues in human neutrophils.
The effect of cystathionine and cystathionine metabolites found in the urine of patients with cystathioninuria on the phosphorylation of tyrosine residues was studied with human peripheral blood polymorphonuclear leukocytes. Among the cystathionine metabolites, cystathionine ketimine markedly increased phosphorylation of a 45 kDa protein with time and the phosphorylation depended on the concentration of cystathionine ketimine, while cystathionine and the reduced form of cystathionine ketimine (cyclothionine) did not increase the phosphorylation of the 45 kDa protein. The phosphorylation of the 45 kDa protein induced by cystathionine ketimine was inhibited by genistein and herbimycin A, inhibitors of tyrosine kinase, but was not inhibited by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine and staurosporine, inhibitors of protein kinase C.
Benzoquinones↗