Glibenclamide-induced photosensitivity in a diabetic patient with erythropoietic protoporphyria.
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Dermatitis, Phototoxic↗
Biomedical subjects
S Fujii
Publications and source records attributed to S Fujii.
Adenocarcinoma of the bilateral fallopian tube occurring after tubal sterilization.
A case of bilateral tubal carcinoma occurring 22 years after tubal sterilization is presented. We believe that this is the first case report of bilateral tubal carcinoma that has arisen in ligated fallopian tubes. The possibility that tubal occlusion is one of the causative factors of tubal carcinoma is discussed.
Adenocarcinoma↗
Human Aortic Vascular Smooth Muscle Cells Digest Extracellular Matrix by Elaboration of Plasminogen Activators: Implications for Atherogenesis.
Migration and proliferation of vascular smooth muscle cells (SMCs) are hallmarks of atherogenesis and restenosis after angioplasty. Digestion of surrounding extracellular matrix (ECM) may be a critical link. To determine whether invasion of ECM by human aortic SMCs (HASMCs) depends on proteolytic digestion mediated by the cells themselves, we characterized ECM digestion in terms of solubilization of 3H-proline--labeled ECM, produced by the use of rat aortic SMCs, by HASMCs under various conditions. Plasmin alone (10 µg/ml) digested 80% of ECM in 2 hours. HASMCs in 10% fetal bovine serum cultured on ECM that was not exposed to plasmin digested 48% of the ECM in 7 days. When HASMCs were cultured on plasmin-pretreated ECM, only 14% of the residual ECM was digested. Conditioned media or cells cultured on porous membrane 1 mm removed from the ECM had no effect. Baseline secretion of tissue-type plasminogen activator (t-PA) into the media by HASMCs averaged 3.9 ng/105 cells/24 hr and baseline secretion of type-1 plasminogen activator inhibitor (PAI-1) averaged 1300 ng/105 cells/24 hr. Thrombin (5 U/ml) increased t-PA antigen production by 184% without altering PAI-1 activity and increased ECM degradation by 43% in 7 days. Transforming growth factor-beta (TGF-beta) decreased t-PA antigen production, increased PAI-1 activity, and decreased ECM degradation. These results suggest that (1) HASMCs can digest naturally produced ECM; (2) plasminogen-dependent mechanisms requiring cell contact are important in the initiation of this phenomenon; and (3) thrombin in the vicinity of clots may modulate the fibrinolytic and proteolytic properties of SMC through t-PA after vascular injury.
Journal Article↗
Acquired idiopathic generalized anhidrosis: clinical manifestations and histochemical studies.
A 40-year-old male developed complete absence of sweating except for slight sweating in the axillar region. Histopathologic examination of the skin revealed lymphocytes infiltration around the sweat glands and coarse and irregular arrangement of the eccrine glands. Immunohistochemical staining using anti-CD3, CD4, and CD8 antibodies revealed that CD3 positive cells were dominant in the lesion. After intensive glucocorticoid treatment, generalized sweating was almost completely recovered.
Adult↗
New phospholipase A2 inhibitor: synthesis and inhibition mechanism of oxazolidinone phospholipid analog.
(R)-3-Dodecanoyl-4-phosphatidylcholino-hydroxymethyl-2-oxazolidino ne (7), which is a new glycerophospholipid analog, was synthesized starting from (S)-glycidol through a 4-alkylsilyoxymethyl derivative and N-acyl-4-hydroxymethyl derivative. The cyclic amide analog 7 showed strong inhibitory activity toward both Group I and II PLA25, but the inhibitory potency of 7 was slightly weaker than that of the linear amide analog (R)-1, which had been developed by de Haas et al. (Biochem. Biophys. Acta 1990, 1043, 67). The interactions of 7 with human secretory PLA2 was investigated by computer modeling in comparison with those of the linear amide analog 1. The results of the computer modeling were very compatible with those of the inhibitory activities toward PLA2S, and the both results showed that the binding mode of the oxazolidinone analog 7 was very similar to that of the genuine substrate and was different from that of the linear amide analog 1.
Computer Simulation↗
Biochemical and topological analysis of adult T-cell leukaemia-derived factor, homologous to thioredoxin, in the pregnant human uterus.
Adult T-cell leukaemia-derived factor (ADF), homologous to thioredoxin, displays various biological activities, such as radical scavenging action and the reduction of protein disulphide bonds. We examined the biochemical and immunohistochemical localization of ADF in the pregnant human uterus, using two heteroantibodies to ADF, antibody C and W. Immunohistochemically, decidua and trophoblast cells were intensely stained by antibody C. The concentration of ADF-like substance in the decidua was 95.9 ng/mg protein, determined by enzyme-linked immunosorbent assay. The molecular weight of ADF-like substance in these tissues was determined by gel electrophoresis to be 13 kDa, the same as that of recombinant ADF. These findings indicate that abundant ADF is present in decidua and trophoblast cells; the localization of such a potent dithiol reducing substance may be beneficial in protecting the fertilized egg and placental trophoblasts from the cytotoxic effects of oxygen radicals.
Adult↗
Binding mode of phospholipase A2 with a new type of phospholipid analog having an oxazolidinone ring.
Inhibition of phospholipases A2 (PLA2s) by a new type of monodispersed phospholipid analog, 3-dodecanoyl-4-phosphatidylcholinohydroxymethyl-2-oxazolidinone (oxazolidinone-PC), was investigated by the pH stat assay method using monodispersed 1,2-dihexanoyl-sn-glycero-3-phosphorylcholine (diC6PC) as the substrate. The PLA2s used were those from bovine pancreas and cobra (Naja naja atra) venom (Group I) and from Japanese mamushi (Agkistrodon halys blomhoffii) venom (Group II). This new-type substrate analog was shown to inhibit competitively both types of venom and bovine pancreatic enzymes by binding to the active site in a similar manner to the carboxamide-type analog 2-dodecanoyl-amino-1-hexanol-phosphocholine (amide-PC). The binding of a stereoisomer, (R)-amide-PC, to N. naja atra (Group I) and A. halys blomhoffii (Group II) PLA2s was facilitated by the binding of Ca2+ to the enzymes. On the other hand, the binding of (R)-oxazolidinone-PC to the N. naja atra (Group I) enzyme was found to be independent of Ca2+ binding, while its binding to the A. halys blomhoffii (Group II) enzyme was markedly facilitated by the binding of Ca2+ to the enzyme. The binding of (R)-amide-PC to N. naja atra PLA2 (Group I) was markedly influenced by the ionization state of the catalytic residue His 48, whereas the binding of (R)-oxazolidinone-PC was found to be practically independent of the ionization state of this residue.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Filtration of human seminal specimens using LeukoSorb leukocyte-retention medium.
OBJECTIVE: To compare LeukoSorb filtration with Percoll centrifugation in preparing sperm. METHODS: Each of 26 human seminal specimens were analyzed before and after two preparation methods. RESULTS: In normospermic specimens (n = 11), LeukoSorb produced higher results than Percoll did with regard to mean percentage of motility (72.7% vs 59.2%), total swollen sperm in a hypo-osmotic swelling test (84.8% vs 59.0%), (g)-type swollen sperm (37.8% vs 23.4%) and tail abnormality (20.4% vs 10.1%). In asthenospermic specimens (n = 15), LeukoSorb produced higher results than Percoll did with regard to mean percentage of motile sperm recovery (22.2% vs 10.1%), motility (46.9% vs 23.2%), viability (75.6% vs 54.7%), total swollen sperm (84.8% vs 59.0%) and tail abnormality (42.2% vs 24.3%), although the mean percentage of head abnormality was lower with LeukoSorb than with Percoll (30.6% vs 40.2%) vs 40.2%). In pyospermic specimens (n = 10), the mean concentration of round cells after LeukoSorb decreased significantly more than with Percoll (p = 0.029). The filtration time correlated with the total sperm concentration. CONCLUSION: LeukoSorb filtration is useful for preparing asthenospermic and pyospermic seminal specimens.
Centrifugation↗
Prediction of histopathologic features and proliferative activity of uterine leiomyoma by magnetic resonance imaging prior to GnRH analogue therapy: correlation between T2-weighted images and effect of GnRH analogue.
To predict the histological features and proliferative activity of leiomyomas and to evaluate the effect of GnRH analogues (GnRHa) by MR images, the correlation between MR images and histopathologic findings was studied on 137 leiomyomatous nodules from 79 patients. The correlation among cellularity, proliferative activity and MR images was studied on sections of 42 leiomyomatous, nodules stained with hematoxylin-eosin and immunohistochemistry for proliferating cell nuclear antigen. The utility of MR imaging in assessing response to therapy with a GnRHa (buserelin 900 micrograms/day, intranasal for 16 weeks) was studied on 62 leiomyomatous nodules from 29 patients. On T2-weighted MR images, we encountered five major images. According to the increase of signal intensity relative to that of the myometrium and/or the endometrium, the images were classified as Type 1, Type 2, Type 3, Type 4, and Type 5. Histopathologically, the majority of Type 1, Type 2 and Type 3 images had features of typical leiomyoma. Almost all cellular leiomyomas and bizarre leiomyomas had Type 4 images. Variable degenerative features were observed in the nodules with Type 5 images. According to the increase of signal intensity, leiomyomas had a tendency to show a high degree of both cellularity and proliferative activity. Moreover, the reduction rate of leiomyomatous nodules after GnRHa therapy correlated with the tumor signal intensity on T2-weighted images before therapy. The reduction rate was the lowest in Type 1 images (20.9%) and the highest in Type 4 images (50.7%). These results suggest that increased the signal intensity on T2-weighted MR images correlates with the cellularity and proliferative activity of leiomyomas, and with tumor response to GnRHa treatment. MR imaging enables quantitative monitoring of GnRHa therapy in patients with leiomyomatous nodules, and allows us to predict the histopathology, cellularity, proliferative activity, and shrinkage rate of nodules before GnRHa treatment.
Adult↗
Reduction of ultraviolet-induced skin cancer in mice by topical application of DNA excision repair enzymes.
Ultraviolet (UV) irradiation produces two major photoproducts, cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts. T4 endonuclease V (T4N5), which specifically repairs CPD, is encapsulated in liposomes. A previous study has shown that UV-induced carcinogenesis in mice was suppressed by the application of T4N5 liposomes. To confirm the suppressive effect, we applied T4N5 liposomes with repeated UVB exposure to hairless mice. At the end of the experiment, mice treated with T4N5 liposomes had 3.5 +/- 1.3 tumors per mouse, and control mice had 6.3 +/- 2.8 tumors per mouse. In addition, the incidence of tumors was reduced in T4N5 liposome-treated mice compared with controls. The pathological diagnosis of the tumors was not significantly different between two groups. Immunohistochemical analysis of p53 protein in UV-induced tumors showed that nearly half of the tumors in both groups were positive. When the biopsied normal-looking skin taken during the experiment was stained with p53 antibody, there was no significant difference of the timing of p53 protein expression between the control mice and T4N5 liposome-treated mice. These results confirmed that CPD plays a pivotal role in UV carcinogenesis, although the molecular mechanisms of the suppression by T4N5 liposomes should be further clarified.
Administration, Topical↗
Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39.
Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer. This mechanism is frequently associated with the impairment of either E-cadherin expression or function. However, mechanisms of such abnormalities have not been fully elucidated. In this study, we demonstrated that the function of E-cadherin was completely abolished in the human gastric cancer cell line HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins, beta-catenin. Although immunofluorescence staining of HSC-39 cells by using an anti-E-cadherin antibody (HECD-1) revealed the strong and uniform expression of E-cadherin on the cell surface, cell compaction and cell aggregation were not observed in this cell. Western blotting (immunoblotting) using HECD-1 exhibited a 120-kDa band which is equivalent to normal E-cadherin. Northern (RNA) blotting demonstrated a 4.7-kb band, the same as mature E-cadherin mRNA. Immunoprecipitation of metabolically labeled proteins with HECD-1 revealed three bands corresponding to E-cadherin, alpha-catenin, and gamma-catenin and a 79-kDa band which was apparently smaller than that of normal beta-catenin, indicating truncated beta-catenin. The 79-kDa band was immunologically identified as beta-catenin by using immunoblotting with anti-beta-catenin antibodies. Examination of beta-catenin mRNA by the reverse transcriptase-PCR method revealed a transcript which was shorter than that of normal beta-catenin. The sequencing of PCR product for beta-catenin confirmed deletion in 321 bases from nucleotides +82 to +402. Southern blotting of beta-catenin DNA disclosed mutation at the genomic level. Expression vectors of Beta-catenin were introduced into HSC-39 cells by transfection. In the obtained transfectants, E-cadherin-dependent cell-cell adhesiveness was recovered, as revealed by cell compaction, cell aggregation, and immunoflourescence staining. From these results, it was concluded that in HSC-39 cells, impaired cell-cell adhesion is due to mutations in beta-catenin which results in the dysfunction of E-cadherin.
Antibodies, Monoclonal↗
Immunohistochemical localization of heat shock proteins HSP70 and HSP90 in the human endometrium: correlation with sex steroid receptors and Ki-67 antigen expression.
Heat shock proteins of 72 kDa and 90 kDa (HSP70, HSP90) have been suggested to be involved in the functional modulation of sex steroid receptors. We examined the immunohistochemical localization of HSP70 and HSP90 in both the functionalis and basalis layers of normal human endometrium during various phases of the menstrual cycle. Topological correlation with localization of estrogen receptors (ER), progesterone receptors (PR), and proliferation-related Ki-67 antigen was also analyzed. HSP70 was expressed in glandular cells of the basalis but not in the cells of the functionalis during the proliferative phase. In the secretory phase, however, glandular cells of both the basalis and functionalis markedly expressed HSP70. Endometrial stromal cells at the basal layer were positive for HSP70, whereas those cells in the functional layer were negative for HSP70 throughout the menstrual cycle. The topological expression of HSP70 in glandular and stromal cells of the basalis was inversely related to Ki-67 localization. Overexpression of HSP70 in the secretory glands was associated with down-regulation of ER and PR. These findings suggest that HSP70 expression is related to either hormonal regulation of cell proliferation and/or down-regulation of sex steroid receptors. HSP90 was strongly expressed in both glandular and stromal cells during the proliferative phase of the menstrual cycle; in the secretory phase, HSP90 expression was weak in both types of the cells. However, no topological difference in HSP90 expression between the basalis and the functionalis was observed.
Adult↗
Inhibitory effect of cilnidipine on vascular sympathetic neurotransmission and subsequent vasoconstriction in spontaneously hypertensive rats.
We reported previously that cilnidipine inhibited increases in blood pressure and plasma norepinephrine (NE) level in response to cold stress in spontaneously hypertensive rats (SHRs). In the present study, we investigated the effect of cilnidipine on sympathetic neurotransmission and subsequent vasoconstriction in SHRs. In pithed SHRs, electrical sympathetic nerve stimulation (ESNS) elevated blood pressure, and this pressor response was abolished by guanethidine. Cilnidipine at 10 micrograms/kg, i.v. and phentolamine at 1 mg/kg, i.v. suppressed the pressor response to ESNS by 28 +/- 6% and 67 +/- 3%, respectively. Neither nifedipine nor nicardipine inhibited it. The pressor response to exogenous NE was not influenced by cilnidipine. alpha, beta-Methylene ATP inhibited the pressor response to ESNS in the presence or absence of phentolamine. Cilnidipine also attenuated the phentolamine-resistant pressor response to ESNS. In SHR mesenteric vasculatures preloaded with [3H]-NE, cilnidipine (10(-7) M) as well as omega-conotoxin significantly inhibited the 3H overflow evoked by periarterial nerve stimulation. In radioligand binding experiments, cilnidipine inhibited [125I]-omega-conotoxin binding to rat synaptosomes, but it did not inhibit [3H]-prazosin binding to rat cortex membranes. These results suggest that cilnidipine may reduce electrically stimulated NE release from the sympathetic nerve endings of SHR vasculatures probably through its N-type Ca channel blocking action and that cilnidipine may also inhibit the vasoconstriction induced by ATP released concomitantly during nerve stimulation.
Animals↗
Optical resolution of 1-arylethanols with a condensed aromatic ring by lipase from Pseudomonas aeruginosa.
Enantioselective syntheses of both enantiomers of 1-arylethanols with a condensed aromatic ring have been done through acetylation of the racemic alcohols with vinyl acetate in the presence of a lipase from Pseudomonas aeruginosa (Toyobo, LIP). The lipase LIP showed high enantioselectivity and reactivity for the title compounds, reacted acetates, and remaining alcohols were obtained with high optical purity.
Acetylation↗
[Reproductive and developmental toxicity studies of montirelin hydrate (1)--Fertility study in rats by intravenous administration].
A study of fertility and early embryonic development to implantation of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats. Male rats were given the drug intravenously from 63 days before mating to the end of mating period and female rats from 14 days before mating to day 7 of pregnancy; the dose levels for both males and females were 0 (control), 0.02, 1 and 50 mg/kg. The females were sacrificed on day 20 of pregnancy for examination of their fetuses. In the 50 mg/kg group, tremor, disappeared within some minutes, was observed during administration period in all animals. Food and water consumptions increased in the females and body weight gain was suppressed in the males. Moreover prolonged estrus cycle was observed at early period of the administration in the females, but it recovered at late period of the administration. However, there were no toxicities in the males and females in the 1 mg/kg or less groups. The drug had no adverse effects on reproductive function of the parent animals, or on development of fetuses. These results show that the NOAEL of montirelin hydrate are 1 mg/kg for general toxicity in parent animals, and 50 mg/kg for reproductive function of the parent animals and for development of fetuses.
Animals↗
[Reproductive and developmental toxicity studies of montirelin hydrate (3)--Teratogenicity study in rabbits by intravenous administration].
A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, during the period of organogenesis was conducted in New Zealand white rabbits. Female rabbits were given the drug intravenously at dose levels of 0 (control), 0.01, 0.1 and 1 mg/kg from day 6 to day 18 of pregnancy. Female rabbits were sacrificed on day 29 of pregnancy for examination of their fetuses. In the 0.1 mg/kg group, food consumption decreased slightly. In the 1 mg/kg group, tachypnea, salivation and rhinorrhea were observed, and body weight and food consumption decreased and water consumption increased. The drug had no effect on the number of corpora lutea and implantations, or on fetal mortality, on fetal body weights, on placental weight, on sex ratio, or on external, visceral and skeletal development of the fetuses. These results show that the NOAEL of montirelin hydrate are 0.1 mg/kg for general toxicity in mother animals, and 1 mg/kg for pregnancy of mother animals and for development of fetuses.
Animals↗
[Reproductive and developmental toxicity studies of montirelin hydrate (4)--Perinatal and postnatal study in rats by intravenous administration].
A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, during the perinatal and lactation periods was conducted in Sprague-Dawley rats. Female rats were given the drug intravenously at dose levels of 0 (control), 0.02, 1 and 50 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. In the 1 and 50 mg/kg groups, food and water consumptions decreased after delivery and the weights of adrenals of the dams increased. In addition, tremor, disappeared within some minutes, was observed during administration period in all dams given 50 mg/kg. Moreover, body weight gain was suppressed after delivery, and the weights of submaxillary glands increased, and the weights of thymus and liver decreased in the dams given 50 mg/kg. The drug did not affect delivery. The drug did not have any adverse effects on the newborn including the number of live newborns, birth index and body weights of live newborn. In the 1 or 50 mg/kg group, body weight gains were suppressed and food consumption decreased in the offspring. The drug did not have any adverse effects on the postnatal development of the offspring such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. These results show that the NOAEL of montirelin hydrate are 0.02 mg/kg for general toxicity in mother animals, 50 mg/kg for reproductive function in mother animals and 0.02 mg/kg for their offspring.
Animals↗
[General aspects of the management for obesity].
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Body Constitution↗