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Biomedical subjects

T Naito

Publications and source records attributed to T Naito.

At least 127 records · Page 7Linked to original sources
PubMed1997

Synthesis and antifungal activity of novel thiazole-containing triazole antifungals.

A new series of thiazole-containing triazole antifungals was synthesized and evaluated for antifungal activity against a variety of clinically isolated pathogenic fungi in vitro and against systemic candidosis in vivo. Among these compounds, (+/-)-1-(2,4-difluorophenyl)-1-[4-(2,4-difluorophenyl) thiazol-2-yl]-2-(1H-1,2,4-triazol-1-yl)ethanol (ER24161) showed the most potent and well-balanced in vitro activities and excellent in vivo efficacy. We also achieved an enantioselective synthesis of the more potent enantiomer of ER-24161.

Animals↗
PubMed1997

Aspirin plus either dipyridamole or ticlopidine is effective in preventing recurrent myocardial infarction. Secondary Prevention Group.

The efficacy of combining antiplatelet agents with low doses of aspirin to prevent cardiac events in patients with myocardial infarction was examined. A total of 1,083 patients with prior myocardial infarction were randomly divided into those who were (618) and were not (465) treated with antiplatelet agents, and observed for 12.5 +/- 18.5 months. Those treated with antiplatelet agents included 113 patients treated with aspirin (50 mg) plus dipyridamole (150 mg/day), 253 treated with aspirin (50 mg) plus ticlopidine (200 mg/day), and 252 treated with only 1 of the 3 antiplatelet agents. Cardiac events, including fatal or nonfatal recurrent myocardial infarction, death by congestive heart failure, and sudden death, occurred in 34 patients (7.3%) in the nontreatment group and in 19 patients (3.1%; p < 0.01) in the treatment group; odds ratio 0.40, 95% confidence interval 0.23-0.71. There were only 2 cardiac events (1.8%) in the aspirin + dipyridamole group (p < 0.05 vs nontreatment group: odds ratio 0.28: 0.08-1.03), and 5 such events (2.0%) in the aspirin + ticlopidine group (p < 0.01; odds ratio 0.28: 0.11-0.69). Subgroup analysis to exclude differences in the patients' background confirmed the efficacy of these antiplatelet agents. We conclude that combined treatment with low doses of aspirin plus either dipyridamole or ticlopidine is effective in preventing cardiac events in patients who have had prior myocardial infarction.

Aged↗
PubMed1997

Oculomotor nerve palsy caused by lung cancer metastasis.

A 39-year-old man with a known diagnosis of lung adenocarcinoma developed intermittent double vision with right pupil dilatation. His symptoms eventually progressed to complete oculomotor nerve palsy on the right. Postmortem examinations revealed a metastasis of the adenocarcinoma involving the root of right oculomotor nerve.

Adenocarcinoma↗
PubMed1997

Elevated sialyl Lewis X-i antigen levels in pleural effusions in patients with carcinomatous pleuritis.

The levels of sialyl Lewis X-i antigen (SLX), which is one of the cancer-associated carbohydrate antigens, were evaluated in 83 malignant and 46 benign pleural effusions. SLX levels in pleural effusion due to lung adenocarcinoma were significantly higher than those due to benign diseases (p < 0.0001), lung cancer other than adenocarcinoma (p = 0.0052), and adenocarcinoma originating from other organs (p = 0.0492). According to receiver operating characteristic (ROC) curve analysis, the optimal cut-off level in the discrimination between malignant and benign pleural effusions was 92 U/ml, which gave a sensitivity of 57.1% and a specificity of 77.8%. The cut-off level of pleural effusion in patients with carcinomatous pleuritis might be higher than that of serum (38 U/ml).

Adenocarcinoma↗
PubMed1997

[Smoldering leukemia with CD7.CD34(+), immunoglobulin heavy chain rearrangement (+) and hypoplastic marrow with myelofibrosis].

A 63-year-old male was admitted because of pneumonia. Peripheral blood findings showed pancytopenia with increase of blasts. A bone marrow specimen showed hypocellular marrow with increase of blasts. The blasts were positive for CD7, CD34, and HLA-DR and negative for other lymphoid antigens and myeloid antigens involving myeloperoxidase. Rearrangement of immunoglobulin heavy chain was demonstrated by Southern blotting analysis. T cell receptor beta, T cell receptor gamma and immunoglobulin light chain rearrangement were negative. A diagnosis of stem cell leukemia was made. In vitro, the blasts did not respond to recombinant human granulocyte colony-stimulating factor (rhG-CSF), cytarabine (Ara-C) and all-trans retinoic acid (ATRA). However, in the blasts of culture without cytokeins, CD33 expression was newly induced. Remission was not obtained by chemotherapies with cyclophosphamide, etoposide, prednisolone and Ara-C. Four months later, marrow specimens showed hypoplasty with myelofibrosis. One year later, the blasts showed CD33 expression with negative myeloperoxidase. The leukemia was transformed to minimally differentiated myeloid leukemia from stem cell leukemia. This condition was thought to be "smoldering leukemia" because of the slow development and refractoriness to chemotherapy. Nineteen months later the patient died due to respiratory failure by pneumonia and pulmonary bleeding despite therapy.

Acute Disease↗
PubMed1997

[Aortic valve insufficiency caused by nonpenetrating chest trauma difficult to distinguish from infective endocarditis with transesophageal echocardiography: a case report].

A 58-year-old man was involved in an automobile accident and suffered remittent fever, leukocytosis and high C-reactive protein level. He developed a diastolic murmur 2 months after the accident. Transesophageal echocardiography showed severe aortic regurgitation with a vegetation-like echo image attached to the right coronary cusp leaflet, suggesting infective endocarditis. Intensive medical treatment for 11 months did not improve the vegetation-like echo-image, so aortic valve replacement was performed. Disruption of the right coronary cusp leaflet was confirmed surgically. Prolapse had occurred as a result of disruption during diastole. The vegetation-like echo-image was considered to be the tip of this leaflet.

Aortic Valve Insufficiency↗
PubMed1997

[Surgery for cholelithiasis in cirrhotic patients].

Although biliary tract surgery for cholelithiasis is performed frequently, cirrhotic patients require special consideration. The prevalence of postoperative severe complications, such as hepatic failure and biliary peritonitis caused by insufficient fistula formation after removal of the T-tube, is higher than non-cirrhotic patients. We suggest that definitive surgery can be carried out safely, in Child's A and B cirrhotic patients, either electively or as an emergency. However, a more conservative approach is advisable in Child's C patients with acute conditions and definitive surgery is recommended as an elective procedure after liver function has improved. And for the treatment of choledocholithiasis in patients with severe cirrhosis, avoiding surgical intervention through the use of such techniques as endoscopic papillotomy is recommended whenever possible.

Adult↗
PubMed1997

Myeloperoxidase antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in a very elderly patient with generalized vasculitis at autopsy.

An 86-year-old woman was admitted with hemoptysis and rapid deterioration of renal function. Renal biopsy disclosed necrotizing crescentic glomerulonephritis. Based on positivity for serum myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA), MPO-ANCA-associated glomerulonephritis was diagnosed. Steroid pulse therapy was performed, but the patient died after the second course. Autopsy revealed renal vasculitis with fibrinoid necrosis extending to the level of the arcuate arteries. Vasculitis was also observed in the liver, adrenal gland, uterus, and spleen, suggesting the presence of microscopic polyarteritis. This case demonstrates the broad spectrum of MPO-ANCA-positive vasculitis and suggests the need for a more effective therapy suitable for very elderly patients.

Aged↗
PubMed1997

[Clinical significance of cytokine measurement in pleural effusion].

We measured the activity of adenosine deaminase (ADA) and the concentration of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the pleural effusions from 28 patients with tuberculosis, 30 with neoplastic diseases, 25 with bacterial infections and 18 with congestive heart failure or liver cirrhosis. The levels of ADA (83.0 +/- 32.1 IU/L) and IFN-gamma (795.0 +/- 666.4 pg/ml) in tuberculous effusions were significantly higher than those in other groups (p < 0.0001). IL-1 beta level in the effusions of bacterial infections (265.2 +/- 379.2 pg/ml) was higher than that in other groups (p < 0.0001). TNF-alpha level in the effusions of tuberculosis (31.7 +/- 36.7 pg/ml) and bacterial infections (69.5 +/- 232.9 pg/ml) was higher than that in other groups. IL-8 level of exudative effusions was higher than that of transudates. IL-2 was only present in 4 effusions from tuberculosis and 1 effusion from bacterial infections. Diagnostic utilities of cytokines and ADA for tuberculous effusion were evaluated using receiver operating characteristics (ROC) curve analysis. The cut-off points of ADA, IL-1 beta, IL-8, TNF-alpha and IFN-gamma determined in this analysis were 54 IU/L, 5.5 pg/ml, 405 pg/ml, 4.5 pg/ml and 28 pg/ml, respectively and the sensitivity and the specificity of them were 88.0% and 95.9%, 19.1% and 74.1%, 57.1% and 63.2%, 81.0% and 77.2%, and 96.2% and 98.5%, respectively. In ADA, TNF-alpha and IFN-gamma, the areas under the curve (AUC) that represent the diagnostic accuracy were 0.968, 0.719 and 0.993, respectively. AUC of IFN-gamma was significantly higher than that of ADA or TNF-alpha. In tuberculous pleural effusion, IFN-gamma was significantly correlated with TNF-alpha, IL-1 beta and ADA. The correlation was also present between TNF-alpha and ADA.

Adenosine Deaminase↗
PubMed1997

[The outcome of patients with mediastinal tumors detected by mass screening versus the outcome of those initially presentating with symptoms].

Forty seven patients with mediastinal tumors, who were diagnosed between 1976 and 1996 at Tsukuba University Hospital, were evaluated according to the circumstances surrounding their initial consultations. The outcome of 19 patients (40.4%) whose tumors were detected by mass screening was compared with the outcome of 20 patients (42.6%) whose tumors were detected after presenting with symptoms. In the mass screening group, only 21% of the patients had a malignant neoplasm, whereas 75% of patients in the symptomatic group had a malignant neoplasm (p = 0.0008). Patients in the screening group had a shorter hospital stay than those in the symptomatic group (60.5 vs. 118. 1days; p = 0.0022). In patients with thymomas, in the mass screening all patients group were at stage I or II. Only 20% of the lesions in symptomatic patients were at stage I or II (p < 0.0001). Based on the results of this study, we believe that the early detection of mediastinal tumors via mass screening might have clinical significance.

Adolescent↗
PubMed1996

TNF-alpha enhances colony-stimulating factor-1-induced macrophage accumulation in autoimmune renal disease.

The lpr mutation on the MRL background accelerates autoimmune nephritis in which macrophage (M phi) accumulation is prominent. Renal disease is absent in other strains with lpr. TNF-alpha and CSF-1 are increased in the kidney of MRL-lpr mice with loss of renal function. We have established that CSF-1 can incite renal injury in mice with the lpr mutation, and M phi from the MRL strain hyper-respond to this growth factor. We hypothesized that TNF-alpha enhanced the M phi response to CSF-1 in MRL-lpr mice. We now report that TNF-alpha enhanced CSF-1-induced bone marrow M phi proliferation in MRL-lpr mice, and not in congenic MRL +/+, normal C3H +/+, and BALB/c, or another strain with lpr (C3H-lpr). Using a gene transfer approach to deliver CSF-1 together with TNF-alpha into the kidney, we evaluated the impact on renal injury. Tubular epithelial cells genetically modified to produce CSF-1 (CSF-1-TEC) and TNF-alpha (TNF-TEC) placed under the renal capsule caused a greater accumulation of M phi in the implant site than CSF-1-TECs alone in MRL-lpr, but not MRL +/+ mice. We noted in tissues adjacent but not distal to the implanted TECs, an increase in M phi in the interstitium and surrounding glomeruli of MRL-lpr but not MRL +/+ mice. This indicated that CSF-1 and TNF-alpha released by TECs were responsible for promoting renal pathology. Taken together, these data suggest that the simultaneous expression of TNF-alpha and CSF-1 in the MRL-lpr kidney fosters M phi accumulation. We speculate that the increase in M phi in the kidney in response to CSF-1 and TNF-alpha is responsible for the rapid tempo of autoimmune renal injury in MRL-lpr mice.

Adjuvants, Immunologic↗
PubMed1996

Enhanced response of macrophages to CSF-1 in autoimmune mice: a gene transfer strategy.

Mice with the MRL background have a genetic propensity for autoimmune lupus nephritis. The lpr mutation on the MRL, but not the C3H background, induces rapid and fatal renal injury in which macrophages (M phi) are prominent. We previously established that CSF-1 accompanies M phi accumulation in the kidney of MRL-lpr mice. Furthermore, CSF-1 introduced into the kidney incites renal injury in mice with the lpr mutation, but not congenic strains. Notably, CSF-1 induces more severe tissue injury in MRL-lpr than in C3H-lpr mice. We hypothesized that M phi from the MRL background respond more readily to CSF-1 than normal strains. We establish herein the following: 1) glomerular M phi and bone marrow M phi (BMM phi) from MRL-lpr mice proliferate similarly to CSF-1; 2) MRL BMM phi proliferate more vigorously to CSF-1 than normal strains (C3H, BALB/c) or another strain with lpr (C3H-lpr); and 3) modulation of CSF-1 receptor expression by CSF-1 is more rapid in MRL than C3H BMM phi. We used a gene transfer strategy to deliver CSF-1 into the kidney to evaluate M phi response to CSF-1. We genetically modified tubular epithelial cells to produce CSF-1 (CSF-1-TECs) and placed these cells with BMM phi under the renal capsule. CSF-1-TEC + BMM phi caused a greater accumulation of M phi in the implant site and interstitium of MRL +/+ than C3H +/+ mice. Furthermore, CSF-1-TEC + BMM phi caused a lesion consisting of M phi in MRL +/+ mice, extending from the implant into the adjacent cortex. We suggest that the response of MRL M phi to CSF-1 is responsible for the notable accumulation of M phi in the MRL-lpr kidney.

Animals↗
PubMed1996

Use of an active center-directed plasmin inhibitor elucidates the multiplicity of plasmin actions.

In our studies, designed to synthesize an active center-directed plasmin (PL) inhibitor, N-(4-aminomethylbenzoyl)-4-(3-picolyloxy)-L-phenylalanine n-hexylamide dihydrochloride (PASI-535) was found. We characterized PASI-535 and analyzed the actions of PL, comparing with those of PASI-535 and tranexamic acid (t-AMCHA). (1) PASI-535 strongly inhibited not only fibrinolysis (IC50: 2.9 x 10(-6) M) but also amidolysis (Ki value: 2.9 x 10(-6) M) and fibrinogenolysis (IC50: 4.5 x 10(-6) M) induced by PL. While t-AMCHA which strongly inhibited fibrinolysis (IC50: 6.0 x 10(-5) M), rarely inhibited amidolysis (Ki value: 4.0 x 10(-2) M) and fibrinogenolysis (IC50: 1.0 x 10(-2) M). (2) PL is able to liberate kinins by degrading kininogen. This kinin-generation by PL was inhibited by 2 x 10(-5) M PASI-535. However, it was little inhibited even by 1 x 10(-3) M t-AMCHA. (3) The inhibitory effect of PASI-535 and t-AMCHA on tumor growth was studied. In sarcoma-180 bearing mice, ascites retention and the increase of tumor cells were markedly suppressed by subcutaneous injection of PASI-535, either 30 mg/kg/day or 50 mg/kg/day, for 5 days, and the inhibitory effect was dose-dependent. Although t-AMCHA also reduced both ascites retention and the increase of tumor cells, it needed approximately 40 times (2 g/kg/day) the amount of PASI-535 to exert these effects. PASI-535 may be a useful tool in analyzing the multiplicity of PL actions. Moreover, PASI-535 can be used as an antifibrinolytic drug which has a mechanism of function different from that of t-AMCHA.

Amino Acid Sequence↗
PubMed1996

Arthrodesis of knee joint by vascularized fibular graft.

Knee arthrodesis has been performed in 17 patients using vascularized fibular graft (VFG); 15 of them could be followed more than 1 year. Twelve were bone defect following tumor resection, two were traumatic bone defect, and one was intractable traumatic non-union. Three types of graft were performed; single VGF as supplement (Type I) in 5 cases, double VFG for femoral defect (Type II) in 8 cases, and double VFG for tibial defect (Type III) in 4 cases. Bone union was achieved in all cases except one. The average time to primary bone union was 4.7 months. Hypertrophy of the graft was observed significantly in some of Type II and in all of Type III. VGF is a useful method for knee fusion in patients with a large bone defect or with an intractable non-union.

Adolescent↗
PubMed1996

Latissimus dorsi musculocutaneous free flap transplantation to salvage below-elbow amputation in an emergency operation: a case report.

We used a free latissimus dorsi musculocutaneous flap (LD m-c flap) to cover a large skin defect at the stump of a forearm in an emergency operation. The patient we discuss is a 52-year-old man. Amputation at the distal one third of the left forearm occurred after catching his hand and wrist in a machine. The amputated left hand was severely damaged and there were wide skin defects. The function of the elbow joint was well preserved. Both the radius and ulna were cut 7 cm distal from the elbow joint. A 20 x 8 cm square of LD m-c flap was transplanted, to the stump of the forearm. The flap survived without incident. The range of motion of the elbow joint was from 20 degrees to 85 degrees. The prosthesis was well fitted to the stump, and the patient returned to his workshop 9 months after injury.

Amputation Stumps↗