A case report of pregnancy in renal transplant recipient treated with FK506 (tacrolimus).
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Adult↗
Biomedical subjects
T Oka
Publications and source records attributed to T Oka.
Negative regulatory element involved in the hormonal regulation of GlcNAc-1-P transferase gene in mouse mammary gland.
The gene encoding UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate transferase (GPT), the enzyme that initiates the pathway for the biosynthesis of asparagine-linked glycoproteins, is ubiquitously expressed in eukaryotic cells. However, its expression in the mammary gland is developmentally and hormonally regulated; transcription of the mouse mammary GPT gene is stimulated by the lactogenic hormones, insulin, glucocorticoid, and prolactin. The involvement of cisacting elements in regulating the expression of the mouse GPT (mGPT) gene was investigated by transient transfections of various GPT promoter/luciferase (Luc) constructs into primary mouse mammary epithelial cells. A series of 5'-deletions of the GPT promoter identified a distal negative regulatory region (base pairs -1057 to -968) and deletion of this region results in enhanced hormonal induction (approximately 7-fold) with no effect on basal promoter activity. Electrophoretic mobility shift assays (EMSA) performed with nuclear extracts from different developmental stages of mouse mammary gland demonstrated that the binding activity of the nuclear proteins to the distal negative regulatory region was predominant in virgin stage as compared with pregnant and lactating stages. EMSA performed with nuclear extracts from virgin explants showed that the binding activity was markedly decreased after cultivation with the combination of the three lactogenic hormones. DNase I footprinting analysis identified two pentamer direct repeat motifs, AGGAA and GAAAC, within the negative regulatory region. EMSA competition experiments showed that mutations within the direct repeats failed to compete for binding of the nuclear proteins to labeled wild type oligonucleotide. Transcription from the promoter containing the mutated direct repeats was increased greatly, consistent with the conclusion that these motifs functions in vivo to repress GPT gene expression. These data suggest the importance of the negative regulatory region in hormonal control of mGPT gene expression in mammary gland.
Animals↗
Repression by a differentiation-specific factor of the human cytomegalovirus enhancer.
We detected a novel nuclear protein, MRF, that binds to multiple sites on the modulator which is located upstream of the human cytomegalovirus major immediate early gene enhancer. The expression of MRF is differentiation specific; the DNA binding activity is present in nuclear extracts from undifferentiated Tera-2 and THP-1 cells, but significantly reduced after these cells are induced to differentiate. In undifferentiated cells the enhancer activity is repressed by the modulator and upon differentiation the enhancer becomes active. Competitive binding assays demonstrate that MRF requires the presence of multiple A+T stretches for binding to DNA, rather than binding to a specific DNA sequence. Mutations of these stretches in the modulator reduce the binding activity of MRF, as well as the repressing activity on the enhancer. These results suggest that MRF may act as a repressor of enhancer function. We propose that MRF binds over the entire modulator and exerts repressor activity.
Base Composition↗
Hormonally regulated double- and single-stranded DNA-binding complexes involved in mouse beta-casein gene transcription.
Transcription of the 252-base pair-long mouse beta-casein gene promoter is induced by the synergistic action of insulin, prolactin, and glucocorticoid in a primary mammary epithelial cell culture. The promoter contains a region termed block C having a highly conserved sequence and position among many casein genes. Mutation of block C reduced the response of the promoter to lactogenic hormones 84%. Nuclear extracts from lactating mouse mammary glands contained both a double-stranded and a single-stranded DNA binding protein complex (DS1 and SS), which specifically bind to the sequences AAATTAGCATGT and CCACAA of block C, respectively. The DS1 and the SS protein complexes were approximately 400 and 280 kDa, respectively. Each complex contained a DNA-binding component(s) having a molecular mass of approximately 120 kDa for DS1 and 80 and 65 kDa for SS. Deoxycholate, which interferes with the protein-protein interactions, inhibited the binding activities of DS1 and SS. The maximal increase in the binding activity of DS1 and SS in the mammary gland occurred during pregnancy and during lactation, respectively. In organ culture, the DS1 activity is increased by epidermal growth factor or prolactin in combination with insulin, whereas the SS activity is enhanced by insulin, prolactin, and glucocorticoid. These results suggest that multiprotein complexes binding to the double- and single-stranded DNA of block C mediate hormonal induction of beta-casein gene transcription.
Animals↗
Pure red cell aplasia induced by FK506.
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Adult↗
Structure of the N intermediate of bacteriorhodopsin revealed by x-ray diffraction.
X-ray diffraction experiments revealed the structure of the N photointermediate of bacteriorhodopsin. Since the retinal Schiff base is reprotonated from Asp-96 during the M to N transition in the photocycle, and Asp-96 is reprotonated during the lifetime of the N intermediate, or immediately after, N is a key intermediate for understanding the light-driven proton pump. The N intermediate accumulates in large amounts during continuous illumination of the F171C mutant at pH 7 and 5 degrees Celsius. Small but significant changes of the structure were detected in the x-ray diffraction profile under these conditions. The changes were reversible and reproducible. The difference Fourier map indicates that the major change occurs near helix F. The observed diffraction changes between N and the original state were essentially identical to the diffraction changes reported for the M intermediate of the D96N mutant of bacteriorhodopsin. Thus, we find that the protein conformations of the M and N intermediates of the photocycle are essentially the same, in spite of the fact that in M the Schiff base is unprotonated and in N it is protonated. The observed structural change near helix F will increase access of the Schiff base and Asp-96 to the cytoplasmic surface and facilitate the proton transfer events that begin with the decay of the M state.
Aspartic Acid↗
Giant hyperplastic polyp of the gallbladder: a case report.
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Adult↗
Preventive effect of hepatocyte growth factor on acute side effects of cyclosporin A in mice.
Cyclosporin A (CsA) is a potent, widely-prescribed immunosuppressant which has serious side effects. When recombinant human hepatocyte growth factor (rh-HGF) was co-administrated with CsA to mice, the severe digestive and/or neurological symptoms and degenerative changes in renal tubular cells and hepatocytes seen with cases of CsA administration were remarkably attenuated and mortality linked to CsA-administration was prevented by rh-HGF. HGF-administration stimulated the DNA synthesis of hepatocytes and renal tubular cells and facilitated reconstruction of hepato-renal tissue structure in vivo. Induction of HGF mRNA expression in the liver and kidney in CsA-administered mice was suppressed in the early stage of organ injury, while HGF mRNA levels increased in the lung three days after CsA-treatment. These observations suggest that the biological action of endogenous HGF is partly impaired after CsA-induced organ injury. Importantly, HGF had no apparent effect on the CsA-induced suppression of interleukin-2 mRNA expression in vitro, thereby indicating that the immunosuppressive potential of CsA was not affected by HGF. Whether or not HGF will prove to have such positive effects in patients requiring CsA-treatment is the subject of ongoing study.
Animals↗
Successful application of an omental pedicle flap in delayed repair of a perforated esophageal diverticulum: report of a case.
Mediastinitis resulting from a perforated esophageal diverticulum is a potentially fatal complication and the surgical treatment of persistent esophagomediastinal fistula may be difficult. In this report, we describe the successful application of an omental pedicle flap in the delayed repair of a perforated esophageal diverticulum. A 53-year-old man presented with chest and back pain and a diagnosis of perforated esophageal diverticulum was subsequently confirmed. After receiving conservative treatment, he was referred to our department and underwent surgical repair 6 months following the onset of the perforation. Through a right thoracotomy, the mucosal layer of the esophagus around the diverticulum was sutured, and an omental pedicle flap was used to cover the suture line and obliterate the fistulous tract. His postoperative course was uneventful and the suture line healed well. The successful treatment of this patient reinforces our belief that wider application of the omental pedicle flap can be expected in the field of thoracic surgery.
Diverticulum, Esophageal↗
In vitro chemosensitivity of human pancreatic cancer cell lines.
CONCLUSION: These results show that eight pancreatic cancer cell lines are broadly sensitive to CDDP, and that chemotherapy for pancreatic cancer may improve the prognosis by more effective drug delivery to cancer cells. BACKGROUND: Chemotherapy for pancreatic cancer does not satisfactorily improve prognosis. The efficacy of chemotherapy depends on choosing sensitive anticancer drugs. METHODS: The in vitro chemosensitivity of eight human pancreatic cancer cell lines was investigated. Growth inhibition was measured by 3H-thymidine incorporation assays for doxorubicin hydrochloride (ADM), mitomycin C (MMC), cisplatin (CDDP), and etoposide (VP-16), and by Alamar Blue assay for (AB assay) 5-fluorouracil (5-FU). The cells were exposed to ADM, MMC, CDDP, and VP-16 for 2 h, and 5-FU for 72 h. From the dose-response curves, the 50% growth inhibition (IC50) level for each drug was estimated. RESULTS: The IC50 after 2 h of exposure of each of the eight kinds of cell lines to each anticancer drug ranged from 0.12-8.2 micrograms/mL for ADM, 0.066-25 micrograms/mL for MMC, 0.57-7 micrograms/mL for CDDP, 0.68-300 micrograms/mL for VP-16. IC50 after 72 h of exposure to 5-FU ranged from 1.8-23 micrograms/mL.
Aged↗
Hyperinsulinaemia accelerates accumulation of cholesterol ester in aorta of rats with transplanted pancreas.
Hyperinsulinaemia may play a role in the development of atherosclerosis; however, the direct effect of endogenous insulin on the atherosclerotic process is not well understood. To clarify this situation we performed pancreas transplantation with systemic venous drainage in Wistar Shionogi (WS) and Spontaneous Hypertensive (SHR) rats. Both rats received syngeneic pancreaticoduodenal transplants from donor rats. SHR rats were used to observe the additive effects of both hypertension and hyperinsulinaemia on the atherosclerotic process. Peak blood insulin levels after a glucose load were approximately two times higher in transplanted rats than in non-transplanted WS and SHR rats. By contrast, there was no difference in plasma glucose responses between transplanted and non-transplanted rats. Hyperinsulinaemia was not related to dyslipidaemia and hypertension in transplanted rats. Nine months after transplantation, the cholesterol ester contents of the aortas of both WS and SHR transplanted rats were significantly higher than in the control rats (WS: 1.9 +/- 1.0 vs 3.8 +/- 2.1 mg/g dry tissue, p < 0.01; SHR: 1.7 +/- 1.3 vs 3.7 +/- 1.4 mg/g dry tissue, p < 0.05). No differences were demonstrated in the thickness of the intima or in the histology of the aortas of transplanted and control rats. To study the mechanism for cholesterol ester accumulation in the arterial wall, we measured neutral cholesterol ester hydrolase activities in vascular medial smooth muscle cells. Insulin significantly suppressed neutral cholesterol ester hydrolase activities in medial smooth muscle cells. Our results indicate that endogenous hyperinsulinaemia contributes to the development of atherosclerosis by accelerating cholesterol ester accumulation in the arterial wall.
Animals↗
Excellent survival in a subgroup of patients with intrapulmonary metastasis of lung cancer.
BACKGROUND: Recently, intrapulmonary metastases in non-small cell lung cancer have been considered to have less influence on prognosis than extrapulmonary metastases. We report a subgroup found among patients with intrapulmonary metastases showing a good prognosis. METHOD: A retrospective study was performed on 236 consecutive patients with non-small cell lung cancer who underwent surgical resection of their tumors. Intrapulmonary metastases were found histopathologically in 50 of them, and their clinicopathologic features were investigated. RESULTS: Analysis of postsurgical results revealed a subgroup of patients showing excellent prognosis (n = 15). They had well-differentiated adenocarcinomas with bronchioloalveolar spread and pT1-2 N0, without vascular or lymphangitic invasion. Their actuarial 5-year survival rate was 100%, with a mean survival interval to date of 28 months. However, none of the other 35 patients survived for 5 years, with a mean survival interval to date of 11 months. CONCLUSIONS: We have clarified that patients with histopathologically diagnosed intrapulmonary metastases from non-small cell lung cancer do not constitute a homogeneous group. Pulmonary metastases with good prognosis, which are considered to be hematogenous metastases, may be benign lesions such as adenomatous or atypical adenomatous hyperplasias mimicking malignant tumors.
Adenocarcinoma↗
Gene analysis of reassortant influenza virus by RT-PCR followed by restriction enzyme digestion.
An amplification system for nearly full length cDNA coding the eight influenza virus segments of A type (H1N1, H2N2, H3N2) and B type influenza viruses is described. Each of the segments of PB1, PB2, PA, NP, M, and NS can be amplified using one 5' primer and one 3' primer for A-type influenza viruses. The RT-PCR amplification system was applied to define the gene composition of three subtype cold-recombinant, live attenuated influenza viruses. Each segment of the attenuated influenza virus could be identified as deriving from segments of the Ca donor or wild virus by comparing the representative restriction enzyme digestion patterns of the three PCR products obtained from the Ca donor, the cold-live attenuated influenza viruses and the wild virus. This RT-PCR method, using RT-PCR followed by digestion of PCR products with restriction enzymes, was very beneficial for analyzing the genome of reassortant influenza viruses.
Base Sequence↗
Tuberculous pseudoaneurysm of the thoracic aorta.
Tuberculous pseudoaneurysm has been reported to be a fatal, but rare complication of tuberculosis. We report a case of a 68-year-old man who underwent successful surgical treatment for a tuberculous pseudoaneurysm of the thoracic aorta with bronchial communication, and review previous reports of patients who also underwent operation for similar lesions, focusing especially on the pathway of infection to the aorta.
Aged↗
Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis.
The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in liver cirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.
Journal Article↗
The hemagglutination inhibition antibody responses to an inactivated influenza vaccine among healthy adults: with special reference to the prevaccination antibody and its interaction with age.
The immunogenicity of the trivalent split-virus influenza vaccine was investigated among 70 healthy adults (mean age: 48.5, range: 36-68). The vaccine antigens were: A/Yamagata/32/89 (H1N1); A/Beijing/352/89 (H3N2); and B/Bangkok/163/90. Regarding the entire sample, the vaccine induced a tenfold or more rise on the average in the hemagglutination inhibition (HAI) antibody to each antigen. The response rates (greater than or equal to a fourfold rise) were about 90% or more among those with a prevaccination titer < or = 1:64 (equivalent to < or = 1:16 on the Western scale; in Japan, the HAI titers are expressed by the final, and not the initial, dilution of the serum; from hereon our findings will be expressed using the Japanese scale), whereas they were 0-50% at > or = 1:128. Thus, the prevaccination titer was negatively associated with antibody induction. The achievement rates (postvaccination titer > or = 1:128) among those with a prevaccination titer < 1:16 remained at 48-68%. Regarding the analysis of variance, a significant effect on antibody induction was indicated for the prevaccination titer (P < or = 0.002), but not for age (P > or = 0.425). The interaction between the prevaccination titer and age was significant for A/Yamagata (P = 0.030), while it was also suggestive for A/Beijing (P = 0.054): as age increased, those with no preexisting antibody (< 1:16) showed greater titer rises, in contrast to the smaller rises among those with a titer > or = 1:16. Based on the attack survey conducted separately, the vaccine efficacy on influenza-like illnesses with fever < or = 37 degrees C and > or = 37.5 degrees C was calculated to be 16% (95% confidence interval: -66% to 57%) and 37% (-55% to 74%), respectively.
Adult↗
Large-scale DNA typing for human platelet alloantigens by PCR-PHFA (preferential homoduplex formation assay).
Alloimmunization against human platelet alloantigens (HPA) is known to be involved in disorders such as neonatal alloimmune thrombocytopenic purpura, posttransfusion purpura, and refractoriness to platelet transfusion therapy. HPA typing is essential in diagnosis and management of patients. Therefore a reliable and speedy method is necessary for HPA typing. We have successfully applied a new DNA typing method, PCR-preferential homoduplex formation assay (PHFA) method, to typing for the HPA-1, -2, -3, -4, -5 and -6 systems. This method is based on DNA strand competition during hybridization under a precisely controlled temperature gradient between a double-labelled amplicon (standard DNA), prepared from biotin- and DNP-labelled primers, and an unlabelled amplicon (sample DNA). The results obtained by PCR-PHFA typing were in good agreement with the allotypes determined by serological typing and by other DNA typing methods. The PCR-PHFA method can be easily automated, is suitable for typing both small and large numbers of samples, and thus is applicable to routine HPA typing.
Antigens, Human Platelet↗
Sick sinus syndrome in association with malignant lymphoma.
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Aged↗