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Biomedical subjects

N Usui

Publications and source records attributed to N Usui.

At least 73 records · Page 4Linked to original sources

[Prognostic significance of CD7 expression in adult acute myeloid leukemia].

To evaluate the prognostic significance of CD7 expression in de novo acute myeloid leukemia (AML), we studied 63 patients with AML who had been admitted to our hospital between September 1989 and January 1996. Even of the patients were later eliminated from the study (9 due to insufficient surface marker analyses, and 2 due to early death). The remaining 52 patients (median age: 42.5 years) were evaluated for morphologic subtype, immunophenotypic classification, complete remission (CR), disease-free survival (DFS) and overall survival (OS). All 52 patients were grouped by the French-American-British classification system: 10 as M1, 16 as M2, 11 as M3, 8 as M4, 5 as M5, and 2 as M6. Ten of the patients expressed CD7 on their leukemia cells (positive rate > or = 25) and were classified as CD7(+)AML, with morphological subtypes as follows: 3 as M1, 6 as M2, and 1 as M3. Thirty-three of the 42 patients with CD7 + AML (78.6%) and 6 of the 10 patients with CD7 + AML (40%) achieved CR. DFS and OS rates for the patients with CD7(+)AML were 22.1% and 35.4%, respectively; those for the CD7(+)AML patients were 53.3% and 44.4%, respectively. No significant differences in gender hematological findings, clinical manifestations such as hepatosplenomegaly, lymphadenopathy, or incidence of central nervous system involvement, CR rate, and DFS distinguished patients with CD7(+)AML from those with CD7(+)AML. These suggest that CD7 expression is unlikely to be a prognostic factor in AML.

Adolescent↗

[Chemotherapy for non-Hodgkin's lymphoma].

This review highlights the role of chemotherapy for intermediate grade non-Hodgkin's lymphoma (NHL) including immunoblastic large cell lymphoma and low grade NHL. The combined modality treatment (CMT) consisting of chemotherapy including adriamycin (ADM) and involved-field irradiation (IFI) is considered standard therapy for localized intermediate grade NHL since a superior outcome (long-term disease-free survival rate is about 80%) can be obtained by CMT. However, developing dose-intensified regimens in initial chemotherapy will change the role of IFI. The phase II study using second and third generation regimens for advanced intermediate grade NHL showed a better outcome than first generation regimen CHOP. Unfortunately, the recent phase III intergroup trial concluded that none of the second or third generation treatment was superior to CHOP, and this regimen is now considered to be standard chemotherapy. However, the cure rate of the CHOP regimen (about 30%) is not satisfactory, and efforts should be underway to develop promising regimens with significantly increased dose intensity. While radiotherapy such as IFI, extended-field irradiation and total lymph node irradiation for localized low grade NHL obtained a more than 50% disease-free survival rate, the role of chemotherapy remains controversial. To date, many randomized trials of single agent chemotherapy regimen, combination chemotherapies with or without ADM, and CMT have shown no overall survival benefit for advanced low grade NHL, so there is no standard therapy for it.

Antineoplastic Combined Chemotherapy Protocols↗

CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival.

Although anatomical barriers and soluble mediators have been implicated in immune privilege, it appears that the apoptotic cell death of Fas+ cells by tissue-associated CD95 ligand (Fas ligand, FasL) is an important component. One clinical example of the function of an immune privileged site is the success of human corneal transplants, where a very high percentage of transplants accept without tissue matching or immunosuppressive therapy. Since the mouse cornea expresses abundant Fas ligand and immune privilege has been implicated in the success of these transplants, we examined the role of FasL in corneal transplantation. Our results show that human corneas express functional FasL capable of killing Fas+ lymphoid cells in an in vitro culture system. Using a mouse model for corneal allograft transplantation, FasL+ orthografts were accepted at a rate of 45%, whereas FasL- grafts, or normal grafts transplanted to Fas- mice, were rejected 100% of the time. Histological analysis found that FasL+ grafts contained apoptotic mononuclear cells indicating the induction of apoptosis by the graft, while rejecting FasL- corneas contained numerous inflammatory cells without associated apoptosis. Taken together our results demonstrate that FasL expression on the cornea is a major factor in corneal allograft survival and, thus, we provide an explanation for one of the most successful tissue transplants performed in humans.

Actins↗

Effects of endotoxin on intestinal hemodynamics, glutamine metabolism, and function.

The purpose of this study was to investigate the intestinal hemodynamics and gut glutamine metabolism during endotoxemia, and their correlation with altered intestinal absorptive capacity and permeability. Seventeen Sprague-Dawley rats were used in the study. The endotoxin group (ENDO) received endotoxin (10 mg/kg intraperitoneally, n = 9), while the control group (CONT, n = 8) received saline injection. Twelve hours later, D-xylose (0.5 g/kg) and fluorescein isothiocyanate-dextran (FITC-dextran, 750 mg/kg) were given by oral gavage. One hour later abdominal aortic (AA) blood flow, superior mesenteric venous (SMV) flow, mean arterial pressure (MAP), central venous pressure (CVP), and SMV pressure (SMVP) were also measured. The MAP, AA, and SMV blood flow decreased (P < 0.05), while the CVP and SMVP increased (P < 0.05) in the ENDO group as compared with the CONT group. The ENDO group showed significant decreases for both intestinal glutaminase activity and net intestinal glutamine uptake (P < 0.05). The D-xylose concentration in SMV decreased significantly (P < 0.05) in the ENDO group as compared with the CONT group. However, the plasma FITC-dextran concentration showed no significant difference between the groups. Endotoxin produced a hypodynamic effect in rats 12 h after intraperitoneal administration in association with both a decreased intestinal glutamine metabolism and an absorptive capacity.

Animals↗

Hyaluronic acid of wound fluid in adult and fetal rabbits.

Fetal wound healing proceeds without fibrosis or scar formation in contrast to adult wound healing. The mechanisms responsible for this remarkable process are mediated in part through a fetal wound extracellular matrix rich in hyaluronic acid (HA). Polyvinylalcohol sponge (PVA) wound implants were placed pervertebrally at 24 days' gestation in fetal (N = 118) rabbits and in adult (N = 44) rabbits, and then harvested at 1, 2, 3, 4, 5, and 7 days postwounding. To analyze the fetal and adult wound matrix, the HA concentration of wound fluid within the PVA sponge was quantitated using a newly developed assay. A significantly increased (P < .05) HA deposition on days 1 through 7 in the fetal wounds was found compared with the adult wound. These observations may suggest an important physiologic role in fetal wound healing by providing a more fluid and malleable matrix. These results, coupled with earlier findings of the lack of an acute inflammatory response in the fetus, further support the hypothesis that fetal response to injury is significantly different from adult response in this prescience of an implanted PVA sponge.

Aging↗

Experience in tracheobronchial reconstruction with a costal cartilage graft for congenital tracheal stenosis.

Although successful surgical management of congenital tracheal stenosis has been reported, it is still controversial as to the best operative procedure. Eleven infants with congenital tracheal stenosis were evaluated to confirm the efficacy of tracheobronchial reconstruction with costal cartilage graft. Symptoms ranged from recurrent respiratory infection to severe respiratory failure. All infants had other congenital anomalies in addition to tracheal stenosis. Notably, five infants had pulmonary artery sling and four infants had patent ductus arteriosus. Definitive diagnosis was made by bronchoscopy, results of which showed complete tracheal rings in all patients with severely compromised tracheobronchial lumens. Five infants had elongated stenosis involving nearly the whole length of the trachea, and five infants had segmental stenosis involving nearly one half the length of the trachea. One infant had bilateral stenosis of the main bronchi. Early experience included two deaths from problems related to the repair. The involvement of the carina and the distal portion of the trachea was associated with increased complications and a higher mortality rate. Currently, our preferred technique facilitated by extracorporeal membrane oxygenation (ECMO) includes carinal reconstruction with a thin-wall intraluminal stent. Bronchoscopy is essential for accurate intraoperative incision of the trachea, post-operative airway management for several weeks, and removal of the intraluminal stent.

Bronchi↗

Nitric oxide inhalation therapy for an infant with persistent pulmonary hypertension caused by misalignment of pulmonary veins with alveolar capillary dysplasia.

Misalignment of pulmonary veins with alveolar capillary dysplasia (MPV) has been reported to be a rare cause of persistent pulmonary hypertension of the newborn (PPHN) and to be fatal despite extracorporeal membrane oxygenation (ECMO). A full-term female neonate with PPHN was brought to the hospital for ECMO therapy at 2 days of age. On the 14th day of life, she was extubated early after the second run of ECMO, and underwent nitric oxide (NO) inhalation therapy in the incubator. She died of catheter-related sepsis on the 61st day of life. After autopsy findings revealed MPV, the longest survival with this disease was documented. NO inhalation therapy in the incubator may provide time for lung transplantation.

Administration, Inhalation↗

Esophageal atresia in Osaka: a review of 39 years' experience.

BACKGROUND: One hundred fifty-nine patients who had esophageal atresia with or without tracheoesophageal fistula have been treated at Osaka University Medical School and its affiliated hospitals since the initial (Japanese) experience of Dr T. Ueda in 1957. METHODS: These cases were divided chronologically into three groups. With earlier recognition of surgical neonates and the development of perinatal care, the long-term survival of these patients has steadily improved over 39 years from 28% in the first period (1957 to 1967) to 80% in the third period (1980 to 1995). Of 141 patients treated in the second and third periods (1968 to 1995), 92 (65.2%) had associated anomalies. Cardiovascular and gastrointestinal malformations were the most frequently seen major anomalies. VATER or VACTER association was seen in 12.8% (18 of 141) of these patients. Survival of these cases according to Waterston risk factors was 100% for group A, 100% for group B, and 50% for group C, whereas the new classification proposed by Spitz showed survival of 92% for group 1, 50% for group 2, and 0% for group 3, showing better differentiation among the three groups. RESULTS: There was a long gap between the proximal and distal esophageal ends in seven patients (type A), in all of whom primary anastomosis was possible after 28 to 128 days of elongation by bouginage. Although the survival of esophageal atresia patients dramatically improved in recent years, there is still a high incidence of early and long-term postoperative complications, ie, anastomotic leakage (26.5%), recurrent fistula (7.2%), anastomotic stricture (49.1%), postoperative pneumonia or atelectasis (57.0%), tracheomalacia (25.8%), and gastroesophageal reflux (52.0%). CONCLUSIONS: Recently, there have been changing patterns in the occurrence of complications, which are mainly attributed to technical improvement, better perinatal care and early recognition of pathophysiologic conditions such as tracheomalacia and gastroesophageal reflux.

Abnormalities, Multiple↗

Sperm nuclear envelope: breakdown of intrinsic envelope and de novo formation in hamster oocytes or eggs.

During fertilisation of a fully mature oocyte, the sperm intrinsic nuclear envelope (SINE) disappears soon after sperm-oocyte fusion. A new nuclear envelope appears around the decondensed sperm chromatin when the oocyte reaches telophase II. Whether the SINE persists or rapidly disappears after sperm entry into immature oocytes or fertilised eggs has been controversial. Nuclear envelopes have been demonstrated around the sperm chromatin, which cannot be decondensed within the ooplasm of these oocytes or eggs, but whether these envelopes are persisting SINEs or newly formed envelopes has been a point of dispute. To resolve this issue, the fate of the SINEs of hamster sperm nuclei was traced after incorporation into immature oocytes at the germinal vesicle stage (GV oocytes) or fertilised eggs at the pronuclear stage (PN eggs). The SINEs disappeared quickly within these oocytes or eggs, like those within maturing or mature oocytes, suggesting that the envelopes around the sperm chromatin must be newly formed after SINE breakdown. To obtain further evidence, a detergent-treated, SINE-free sperm nucleus was injected into a PN egg. A new envelope appeared around the still-condensed or partially decondensed sperm chromatin within 3 h after injection. Thus, disassembly of the SINE within ooplasm, unlike that of nuclear envelopes of other cells at prophase, is independent of the cell cycle stage of the oocyte or egg, whereas the ability of the ooplasm to assemble the new envelope is restricted to certain periods of the cycle, i.e. early prophase and telophase during meiosis and interphase, periods when active M-phase promoting factor (MPF) is absent from the ooplasm.

Animals↗

Differential effects of HSV-1 and HCMV infection on adhesion molecule expression on human corneal keratocytes.

PURPOSE: Previous studies have shown that keratoplasty buttons obtained at surgery from patients with herpes simplex virus-1 (HSV-1) keratitis have elevated localized expression of the adhesion molecule ICAM-1, which plays a critical role in the initiation and amplification of an immune response. We performed studies to determine whether changes in expression of ICAM-1 and HLA class I are direct effects of productive infection of human corneal fibroblasts with HSV-1. METHODS: Immunocytologic and flow cytometric analyses were performed to analyze the ability of HSV-1 to induce ICAM-1 and HLA class I expression in a primary cornea-derived keratocyte cell line, E-2. Positive controls for these experiments were E-2 cells infected with human cytomegalovirus (HCMV), which has been shown to increase ICAM-1 expression in selected cells, and E-2 cells treated with IFN-gamma, which upregulates both ICAM-1 and HLA class I expression in most cell types. RESULTS: Kinetic cytometric analysis indicated decreased ICAM-1 expression 3 hours following HSV-1 infection of E-2 cells. In contrast, HCMV led to detectable increases in ICAM-1 expression starting 6 hours after infection. Infections with either HSV-1 or HCMV resulted in reduced HLA class I expression on E-2 and SF cells. CONCLUSIONS: These studies suggest that increased ICAM-1 expression seen on corneal stromal cells during clinical HSV-1 infection is not a direct result of productive viral infection, but of other mechanisms such as cytokine release by infiltrating mononuclear cells.

Adolescent↗

[A coagulation of fibrinolytic study in children with nephrotic syndrome: evaluation of hypercoagulability by measuring with plasmin- alpha 2 plasmin inhibitor complex and FDP D-dimer].

Increased plasma plasmin-alpha 2 plasmin inhibitor complex (PIC) and FDP D-dimer (D-dimer) reflect in vivo activation of the coagulation and fibrinolytic systems. We measured plasma PIC, D-dimer and other coagulation and fibrinolytic parameters in 42 children with nephrotic syndrome. Higher levels of both plasma PIC (0.67 +/- 0.48 micrograms/ml, P < 0.01) and D-dimer (154 +/- 105 ng/ml, P < 0.001) were observed at the active stage of nephrotic syndrome, compared to the remission stage (0.43 +/- 0.18 micrograms/ml, 72 +/- 48 ng/ml, respectively). In addition, plasma D-dimer correlated significantly with serum albumin, urinary protein, plasma fibrinogen, aPTT, and plasma antithrombin III activity. Although no thromboembolic complication was diagnosed clinically in the study period, increased plasma PIC or D-dimer may reflect a hypercoagulable state or subclinical thrombosis in nephrotic syndrome.

Adolescent↗

Morphological differences in nuclear materials released from hamster sperm heads at an early stage of incorporation into immature oocytes, mature oocytes, or fertilized eggs.

To elucidate the effects of ooplasmic factors on the early morphological changes in hamster sperm heads within the ooplasm, immature ovarian oocytes at the germinal vesicle stage (GV oocytes), ovulated fully mature oocytes, and fertilized eggs at anaphase II or the pronuclear stage (PN eggs) were examined in detail 15-30 min after insemination or reinsemination. Thin-sectioning studies demonstrated distinct materials released from the sperm nucleus over the entire postacrosomal nuclear surface immediately after disappearance of the sperm nuclear envelope. The release occurred in all of the oocytes and eggs prior to or even in the absence of subsequent chromatin decondensation. Depending upon the stage of the penetrated oocyte or egg, however, the materials varied in morphology: several hemispherical projections of amorphous material within mature oocytes; a number of electron-dense globules within GV oocytes and PN eggs; and both forms within eggs at anaphase II-telophase II. These observations and the fact that only the release of the amorphous material was accompanied by sperm chromatin decondensation indicate that this release was the initial process of chromatin decondensation, whereas the release of the globules resulted from a deficiency or lack of ooplasmic factors affecting the sperm nucleus. Restriction of the release in both forms of material to the late meiotic phase suggests changes in the factors associated with progression of meiosis. To approach an understanding of the mechanism of successful decondensation of sperm chromatin, the ooplasmic factors considered responsible for the stage-dependent release of nuclear materials are discussed.

Animals↗

Antitumor effects of human recombinant interleukin-1 alpha and etoposide against human tumor cells: mechanism for synergism in vitro and activity in vivo.

Recombinant human interleukin 1 alpha (rh IL-1 alpha) and etoposide (VP-16) synergize for direct growth inhibition of several human tumor cell lines in vitro. Our previous studies demonstrated that VP-16 increased the number of membrane-associated IL-1 receptors (IL-1Rs) and also enhanced the internalization of receptor-bound rh IL-1 alpha. The purposes of this study were to test our hypotheses that these events were critical to the synergy between rhIL-1 alpha and VP-16, to determine whether rhIL- 1 alpha and VP-16 synergize to increase superoxide (SO) anion radical production in vitro since SO anion has been implicated in the toxic effects of IL-1, and to investigate the antitumor efficacy of the combination against tumors in vivo. A375/C6 melanoma cells and OVCAR-3 ovarian carcinoma cells were tested with IL-1 receptor antagonist (IL-1 ra) before exposure to rhIL-1 alpha, VP-16 and rhIL-1 alpha plus VP-16. The synergistic or antagonistic effects were assessed by MTT assay. SO production was measured by reduction of cytochrome C. Athymic female mice bearing the A375/C6 melanoma were treated by rhIL-1 alpha, VP-16, and rhIL- 1 alpha+VP-16. The antitumor effects were evaluated by quantitating tumor growth and survival time. Pretreatment with the IL-1ra abrogated the synergistic effects of rhIL-1 alpha and VP-16. The production of SO radical by A375/C6 cells was increased 2.5 fold by the combination of rhIL-1 alpha and VP-16, and the addition of exogenous SOD blocked the synergy between rhIL-1 alpha and VP-16. However, when A375/SOD15 cells which over-expressed manganese superoxide dismutase (MnSOD) after MnSOD cDNA transfection were exposed to rhIL-1 alpha and VP-16, in vitro antagonism was observed. In vivo studies demonstrated that the combination of rhIL-1 alpha and VP-16 delayed tumor growth better than either agent alone, although long-term survival was not improved because of substantial toxicity. Our results suggest that the synergistic antitumor effects of IL-1 alpha and VP-16 may be due to IL-1R modulation and increased internalization of IL-1-IL-1R complex by VP-16 treatment, as well as to a subsequent increase in SO anion radical production from the tumor cells exposed to both drugs. Thus, the combination of IL-1 alpha and VP-16 might prove useful for the treatment of malignant disease in vivo, if the increased toxicity can be reduced or managed.

Animals↗

Anomalies of the tracheobronchial tree in patients with esophageal atresia.

To examine associated anatomic anomalies of the tracheobronchial tree and structural abnormalities of the trachea, and their clinical consequences, bronchoscopic examination and follow-up studies were performed in 32 patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) over a 5-year period. To evaluate structural abnormalities of trachea, the ratio of circumferential length of cartilaginous trachea to circumferential length of membranous trachea (C:M ratio) was determined before surgical repair. In patients examined before and after surgical repair, the motion of the posterior tracheal wall was observed under spontaneous respiration. Fifteen of the 32 patients (47%) had abnormalities of the tracheobronchial tree such as ectopic right upper bronchus (12), congenital bronchial stenosis (4), and absence of the right upper bronchus (2). The C:M ratio of the 27 patients with EA (2.0 +/- 0.6) was significantly lower than that of controls (3.0 +/- 0.3); the ratio for the 10 cases with ectopic right upper bronchus (1.7 +/- 0.4) was significantly lower than that of other cases (2.2 +/- 0.5). The C:M ratio for the 12 patients who had atelectasis (1.7 +/- 0.3) was significantly lower than that of the 15 who did not have atelectasis (2.2 +/- 0.6). Of 24 infants, nine had bulging of the posterior tracheal wall synchronized with expiration, and their C:M ratio (1.8 +/- 0.2) was significantly lower than that of the 15 patients without bulging (2.2 +/- 0.6). These data show an association between anatomic anomalies of the tracheobronchial tree and structural abnormalities of the trachea in patients with EA. Because these abnormalities may be related to the occurrence of respiratory disorders such as tracheomalacia and atelectasis, early bronchoscopic examination, including measurement of the C:M ratio and observation of the motion of the posterior tracheal wall under spontaneous respiration, may be useful in the care of patients with EA.

Bronchi↗