Squamous cell carcinoma of the endometrium with human papillomavirus type 31.
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Biomedical subjects
Publications and source records attributed to T Nishida.
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Identification of the MAGE genes allowed us the molecular approach to identify genes encoding tumor rejection antigens expressed on human cancer cells. MAGE-1 proteins are normal tissue antigens compartmentalized in the particular testicular cells playing an important role in the early phase of the spermatogenesis. The MAGE-1, -2, -3, -4 and -6 genes are preferentially expressed in many different cancers at both the mRNA and protein levels. The MAGE genes, particularly MAGE-1, became positive in relatively advanced stages of cancers and recurrent cancers. Approximately one-third to half of human cancers except for myelo-monocytic leukemia expressed at least one of these MAGE genes. The MAGE gene products shall be appropriate target molecules for development of new cancer vaccine.
A 66-year-old woman was operated on aortic valve replacement, mitral valve replacement, and tricuspid annuloplasty. Retrieval of remaining Swan-Ganz Thermodilution catheter in the superior vena cava and the right atrium for 15 years was also made. Fortunately, contamination and embolism have not occurred for 15 years. Extracted catheter showed to be stiff due to the degradation. It was suggested that the cause of remaining was the thread for closing the left atrium on the previous operation. The explanation to patient and one's recognition are most important. We recommend that retrieval of remaining catheter for a long time and/or after open heart surgery should be made under extracorporeal circulation because that remaining catheter may be involved with the intima, and preventing from bleeding.
We examined the use of an abdominal wall retraction method instead of pneumoperitoneum in laparoscopic cholecystectomy for patients with cardiac disease to prevent the hemodynamic deterioration associated with pneumoperitoneum. Eight patients with cardiac diseases, mainly valvular or coronary artery diseases, underwent laparoscopic cholecystectomy under hemodynamic monitoring. Five patients without cardiac disease served as controls. As hemodynamic parameters, heart rate, mean systemic arterial pressure (mAP), mean pulmonary arterial pressure (mPAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) were measured. The patients with cardiac disease showed significantly elevated mPAP and PCWP compared with the control group under pneumoperitoneum, and one patient showed critically decreased CI due to increased tricuspid regurgitation under pneumoperitoneum. These changes, however, were resolved on the abdominal wall retraction. There was no major perioperative complication. This abdominal wall retraction method is, therefore, favorable for patients with underlying cardiac disease to minimize the hemodynamic deterioration during laparoscopic cholecystectomy.
A 46-year-old woman was hospitalized for aortic valve stenosis (AS) associated with systemic lupus erythematosus (SLE) on April 12, 1996. She had a syncopal episode six months before admission. She was found to have thrombocytopenia, and was diagnosed with SLE by further examination. Irregular genital bleeding was also seen on admission while her SLE was being controlled with steroid therapy. Aortic valve replacement was performed after the steroids had been reduced to avoid excessive bleeding. The aortic valve was the bicuspid with raphe. There was much calcification on the cusps and the annulus, but there were no degenerative changes. The postoperative course was uneventful, and her SLE has been in remission two years after the operation. The management of steroid therapy for SLE patients complicated with cardiovascular disease is discussed.
Modification effects of low hyperthermia (40 degrees C) on cellular chemosensitivity to bleomycin (BLM), and of BLM on thermosensitivity (40 degrees C) were investigated in cultured murine L cells with simultaneous or sequential treatments of these two agents. The heating of L cells at 40 degrees C up to 6 hours resulted in no remarkable lethal damage. Treatment with low hyperthermia followed by BLM for 4 hours showed no more than additive effect. However, a significant chemical (BLM) enhancement effect on the cellular thermosensitivity was observed by the treatment with BLM for 4 hours prior to the low hyperthermia at 40 degrees C. No appreciable thermal enhancement effect on the cellular chemosensitivity to BLM was shown by preheating at 40 degrees C for 3 hours, while post-heating at 40 degrees C showed a significant thermal enhancement effect as well as in the simultaneous treatments. The cell phase response to BLM was levelled in the clinical range of the doses. It is possible that the repair of sublethal damage (SLDR) from treatment with BLM was inhibited by 40 degrees C post-heating and this SLDR was completed at 3 hours of the interval at 37 degrees C between BLM and 40 degrees C heating.
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Neurotrophic keratopathy, which often follows damage to the trigeminal nerve, is clinically characterized by various types of epithelial disorders and melting of corneal stroma. To understand both the pathology of neurotrophic keratopathy and the physiological significance of corneal sensation, we investigated both the cellular and molecular functions of a sensory neurotransmitter, substance P, in corneal epithelial cells. Our findings prompted us to try a new mode of treatment for neurotrophic keratopathy. Substance P, a member of the tachykinin family, is an 11-amino-acid peptide. In an organ culture system using rabbit corneas, substance P alone had no effect on corneal epithelial migration. In the presence of insulin-like growth factor-1 (IGF-1), however, substance P synergistically facilitated corneal epithelial migration in proportion to the concentration of substance P or of IGF-1. Other neurotransmitters (acetylcholine, norepinephrine, serotonin etc.) or tachykinins (neurokinin A, eledoisin etc.) did not show this synergistic effect with IGF-1. Among receptors for the tachykinin family (NK-1, NK-2, or NK-3) only the NK-1 receptor system was involved in the synergistic effect of substance P and IGF-1 on corneal epithelial migration. IGF-1 affected neither the binding constant nor the number of sites of substance P receptors in corneal epithelial cells, suggesting that the synergistic effect was not regulated at the receptor level. Various extracellular signals activate the intracellular signal transduction system, thus amplifying specific biological functions. We found that the addition of inhibitors of protein kinase C or tyrosine kinase clearly inhibited the synergistic effect of substance P and IGF-1 on corneal epithelial migration, demonstrating that protein kinase C and tyrosine kinase are involved in the synergistic effect. During corneal epithelial wound healing, epithelial cells must attach to a provisional, extracellular fibronectin matrix. We previously reported that interleukin 6 and epidermal growth factor (EGF) facilitate corneal epithelial wound healing by activating the expression of fibronectin receptor (integrin). Reverse transcription-polymerase chain reaction (RT-PCR) revealed that substance P and IGF-1 increased expression of mRNA for integrins alpha 5 and beta 1 in cultured corneal epithelial cells and also increased the number of cells that attached to a fibronectin matrix. These findings strongly suggest that substance P and IGF-1 synergistically increase corneal epithelial migration by activating the expression of integrin. Tachykinins share a five amino acid sequence, phenylalanine-free amino acid-glycine-leucine-methionine amide (FXGLM), at the C-terminus. Studying substance P, we found that a four amino acid sequence at the C-terminus, FGLM, was the minimum amino acid sequence for the synergistic effect on corneal epithelial migration. Structurally similar tetrapeptides mimicking other members of the tachykinin family isoleucine-glycine-leucine-methionine amide (IGLM), valine-glycine-leucine-methionine amide (VGLM), tyrosine-glycine-leucine-methionine amide (YGLM), and the tripeptide glycine-leucine-methionine amide (GLM) did not have any synergistic effect with IGF-1. Based on these findings in vitro, we investigated the effect of eye drops containing substance P plus IGF-1 or FGLM plus IGF-1 on the epithelial wound closure of rabbit corneas in vivo. Both combinations significantly facilitated corneal epithelial wound closure. In a clinical setting, the administration of substance P plus IGF-1 effectively treated corneal epithelial defects in a patient with Riley-Day syndrome, a disease in which corneal epithelial defects persist because of loss of corneal sensation and hypolacrimation. In a patient with neurotrophic keratopathy due to trigeminal nerve paralysis following surgery, eye drops containing FGLM plus IGF-1 eliminated superficial punctate staining. (ABSTRACT TRUNCATED)
We have established a novel method of gene introduction into eukaryotic cells by trans-kingdom conjugation between Escherichia coli/Agrobacterium tumefaciens bacteria and yeasts. To expand this to animal cells, we have constructed a novel conjugative plasmid, pBASGreen which contains SV40-ori/promoter, pUC-ori, IncQ type oriT/mob, Apr and Neor genes with GFP (green fluorescent protein) gene as a reporter. The introduction into COS1 and NIH3T3 animal cultured cells by conventional transfection was easily detected by fluorescence of the GFP gene product under a fluorescent microscope and the transfectants were effectively selected by the Neor marker. By the action of oriT/mob in the presence of tra genes on a helper plasmid, pBASGreen was directly mobilizable from E. coli into animal cells by trans-kingdom conjugation.
BACKGROUND: The prevention of ventricular and vascular dysfunction has been recognized as an important factor in heart preservation. Because lipid peroxidation may cause cell membrane injury after ischemia and reperfusion, we hypothesized that the administration of a lipid peroxidation inhibitor lazaroid (U74500A) would result in an improvement of functional recovery after the 24-hour preservation period. METHODS AND RESULTS: An isolated rabbit heart preparation perfused with support rabbit blood was used. Before preservation, 4 mg/kg of either lazaroid or solvent was given to donor rabbits. The hearts were preserved with University of Wisconsin solution for 24 hours at 0 degree C. The working model preparation (n = 7 in each group) showed a better cardiac output (74.6 +/- 25.7 versus 192.7 +/- 19.6 mL/min, P < .0001) and a lower lipid peroxide level (2.1 +/- 1.3 versus 0.6 +/- 0.3 nmol/mL. P < .05) of the coronary effluent in the heart treated with lazaroid. With a Langendorff preparation (n = 7 in each group), we evaluated the vascular dilatory function. The endothelial function assessed by the percentage increase of coronary flow in response to acetylcholine in the solvent group was significantly lower than that of the lazaroid group (69 +/- 24% versus 140 +/- 67%, P < .05), whereas no significant difference was observed between the groups regarding endothelium-independent vasodilatation as assessed by the responses to nitroglycerin and nitroprusside. CONCLUSIONS: These results demonstrated an improved ventricular and endothelial function in the rabbit pretreated with lazaroid before preservation accompanied by a reduction of lipid peroxidation, indicating the potential benefits for long-term heart preservation.
Previous studies have found nbl expression to transiently rise and fall during glucocorticoid-induced thymic apoptosis. This induction of apoptosis is blocked by the transcriptional inhibitor actinomycin D. However, actinomycin D can trigger apoptosis in other cell types, e.g., HL-60 cells. This study found that internucleosomal DNA cleavage typical of apoptosis is induced by actinomycin D in cell lines such as HL-60 which constitutively express high levels of nbl above a certain "threshold." In contrast, "DNA ladder" formation was not induced by actinomycin D in cell lines with low constitutive nbl expression. Enhanced nbl expression therefore appears to be associated with apoptosis which is either blocked or induced by actinomycin D.
Lazaroid, an inhibitor of iron-mediated lipid peroxidation, has been shown to reduce free radical-mediated injury after ischemia and reperfusion. We thus examined the efficacy of pretreatment with lazaroid (U74500A) in enhancing functional recovery after 24-hr heart preservation. An isolated rabbit heart model perfused with the blood from a support rabbit was used. Before preservation, either U74500A (4 mg/kg, group L; n = 6) or solvent (group S; n = 7) was given to the donor rabbit. After 24-hr preservation with UW solution at 0 degrees C, all hearts were perfused with cross-circulated blood for 60 min with the Langendorff mode followed by 40 min of the working mode. In group S, ventricular fibrillation (Vf) after reperfusion was observed in all hearts, whereas no Vf was observed in the U74500A-pretreated group. In group L, the serum creatine phosphokinase; its isozyme, troponin-T; and serum lipid peroxide levels after 10 min of reperfusion were all significantly (P < 0.05) lower than those in group S. The Frank-Starling curve (indicating the left atrial pressure-aortic flow relationship) showed a significant left and upward shift in group L compared with that in group S (P < 0.0001). The heart pretreated with U74500A showed less ischemia-reperfusion injury, better ventricular function, and a lower lipid peroxide level. We thus conclude that the inhibition of lipid peroxidation with lazaroid appears to offer some potential benefits for long-term heart preservation.
The objective of this study is to clarify to what extent the accumulation of liposomes from the blood into the tumor and bone marrow can be controlled by liposome size and membrane fluidity. Liposomes with different diameters (50-400 nm) and different membrane fluidity were prepared from hydrogenated egg phosphatidylcholine (HEPC) or egg phosphatidylcholine (EPC), cholesterol (Ch) and dicetylphosphate in various molar ratios. These liposomes were injected intravenously into rats bearing Yoshida sarcoma, and the ratios of the accumulation of liposomes in the tumor to those in the bone marrow, liver and spleen were compared. The tumor-to-bone marrow accumulation ratio increased with the decrease in liposome size from 400 to 50 nm. This ratio was greater than those for the liver and spleen at all sizes. Although tumor-to-liver accumulation ratios of 50- and 100-nm HEPC-containing liposomes were higher than those of EPC-containing liposomes, no obvious difference in tumor-to-bone marrow or tumor-to-spleen accumulation ratios was found between these liposomes. Tumor-to-bone marrow accumulation ratio of HEPC-containing liposomes increased remarkably with the decrease in Ch content from 40 to 30 or 20 mol% compared with ratios for the liver and spleen. Interestingly, the tumor uptake clearance of liposomes of the same size was constant regardless of their membrane fluidity. These findings show that the increases in these accumulation ratios are due to their decreased uptake clearance by the bone marrow. Furthermore, the uptake of 50-nm HEPC-containing liposomes by the bone marrow was specifically inhibited by preinjection of other liposomes, but not when they were exposed in advance to in vivo components. These observations suggest the involvement of in vivo component(s) in the uptake of these liposomes by the bone marrow. We conclude that small HEPC-liposomes with low Ch content show their significantly decreased uptake by the bone marrow due to their decreased recognition by this tissue.
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We find that substance P (SP) and insulin-like growth factor-1 (IGF-1) demonstrate a synergistic effect on the stimulation of rabbit corneal epithelial migration in an organ culture. The addition of either SP or IGF-1 alone did not affect epithelial migration, while the combination of SP and IGF-1 stimulated epithelial migration in a dose-dependent fashion. The synergistic effects of SP and IGF-1 on corneal epithelial migration were nulled by the addition of a SP antagonist or enkephalinase. Among neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acethylcholine chloride, norepinephrine, serotonin) or tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin), only SP demonstrated a synergistic effect with IGF-1 on cellular migration. In contrast, the combination of SP and IGF-1 did not affect the incorporation of 3H-thymidine into corneal epithelial cells. The attachment of the corneal epithelial cells to fibronectin, collagen type IV, and laminin matrices increased after treatment of the cells with SP and IGF-1, but SP or IGF-1 by themselves did not affect the attachment of the cells to these extracellular matrix proteins. An identical synergistic effect on corneal epithelial migration was observed when an NK-1 receptor agonist was used in place of SP, suggesting the synergistic effect of SP and IGF-1 might be mediated through the NK-1 receptor system. These results suggest that the maintenance of the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors.
To examine the significance of physiologic and biochemical variables in liver trauma quantitatively, and to establish the early predictors of mortality according to the causes of death, 36 consecutive patients who underwent surgery for liver trauma between 1984 and 1993 were retrospectively studied. A univariate analysis revealed that shock, preoperative systolic blood pressure (SBP), preoperative alanine aminotransferase (ALT), the number of associated organ injuries, the Glasgow Coma Score (GCS), blood replacement requirements, and postoperative blood urea nitrogen (BUN) were significant prognostic factors of survival after liver trauma. However, a multivariate analysis indicated that GCS, postoperative BUN, the number of associated organ injuries, preoperative ALT, and SBP were independent prognostic factors. Because the causes of death after liver trauma can be divided into early hemorrhage and late sepsis, a multiple regression analysis of preoperative and postoperative variables was performed for each cause. The prognostic factors for hemorrhagic death were preoperative ALT, base excess, and the platelet count, whereas those for death due to sepsis were preoperative SBP and the presence of gastrointestinal injuries. These results suggest the value of measuring the preoperative serum level of ALT as a new independent prognostic factor for predicting overall and hemorrhagic death following severe liver trauma.
The effects of pneumoperitoneum on the lower esophageal sphincter (LES) were evaluated during laparoscopic operation for esophageal achalasia. Intraoperative manometry was performed in three patients who underwent laparoscopic cardiomyectomy with Dor's fundoplication and five patients who underwent laparoscopic cholecystectomy (LC). The LES pressure and the length of the high-pressure zone (HPZ) did not change during pneumoperitoneum in either the achalasia and the LC group. In the achalasia group the LES pressure was sufficiently decreased following completion of cardiomyectomy, and the length of the HPZ was found to be sufficiently long after completion of fundoplication. The postoperative courses of the achalasia patients were uneventful, and they have had no symptoms of achalasia or gastroesophageal reflux since the operation. Accordingly, intraoperative manometry during 12 mmHg pneumoperitoneum was considered to be available for laparoscopic surgery for esophageal achalasia.
A 33-year-old man was hospitalized with right heart failure. He was diagnosed as having right atrial mural thrombus complicated with pericarditis on echocardiography, thoracic computed tomography, and cardiac catheterization. Pericardiectomy and thrombectomy with a partial resection of the right atrial wall were performed under extracorporeal circulation. It was suggested that the cause of right atrial thrombus was congestion, atrial fibrillation, and pericarditis. The cause of pericarditis could not be determined by pathologic examination and laboratory data. Surgical treatment should be performed as soon as possible to prevent pulmonary embolism.