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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 505 records · Page 28Linked to original sources

Hyperacute xenorejection of guinea pig-to-rat lung transplantation can be attenuated by blood which has perfused another xenograft.

In discordant xenotransplantation, the recipientOs blood initiates hyperacute xenorejection (HXR). We hypothesized that HXR-related lung edema may be reduced if a new xenograft is perfused by blood which previously has perfused another xenograft. In a syngeneic control group (n = 6), a rat lung (lung XR) was perfused by rat blood (blood AR), following which the blood was collected (blood BR). After another rat lung (lung YR) was perfused by blood BR, the blood was collected (blood CR). In a xenogeneic experimental group (n = 6), a guinea pig lung (lung XG) was perfused by rat blood (blood AG), and the blood was collected (blood BG). Then, another guinea pig lung (lung YG) was perfused by blood BG, and once more the blood was collected (blood CG). White blood cells (WBC), polymorphonuclear leukocytes (PMN), red blood cells (RBC), hemoglobin, hematocrit, and complement (CH50) in the blood were measured pre- and post-perfusion. The wet/dry weight ratio (W/D) of the lung was calculated after the perfusion. WBC and PMN were higher in blood CR/BR than in blood BR/AR. CH50 was higher in blood CG/BG than in blood BG/AG. RBC, hemoglobin, and hematocrit were not different among the blood AR, BR, CR, AG, BG, and CG. The W/D was not different between lung XR and lung YR. The W/D of lung YG was lower than lung XG. In conclusion, the lung edema associated with HXR is reduced when blood which has perfused another xenograft is used to perfuse the new xenograft without anemia, and complement plays a critical role in reducing lung edema.

Acute Disease↗

Basis for dosing time-dependent changes in the antiviral activity of interferon-alpha in mice.

The influence of dosing time on the pharmacological effect (antiviral activity) of interferon-alpha (IFN-alpha), and the pharmacological and pharmacokinetic mechanisms, were investigated in ICR male mice under a 12-h light/dark cycle (lights on from 7:00 AM to 7:00 PM). 2'-5'Oligoadenylate synthetase activity in plasma at 24 h after IFN-alpha (10 MI.U./kg, i.v.) injection, as an index of antiviral activity, was significantly higher for injections given at 9:00 AM than for injections given at 9:00 PM (P <.05). The uptake of [(3)H]thymidine by lymphocytes after 24-h incubation with IFN-alpha, as an index of lymphocyte-stimulating effect, was significantly higher in cells obtained at 9:00 AM than in the cells obtained at 9:00 PM (P <.01). The number of receptors per cell and the expression of interferon-stimulated gene factor in lymphocytes after 24-h incubation with IFN-alpha were significantly higher in the cells obtained at 9:00 AM than at 9:00 PM (P <.05). A significant dosing time-dependent difference was demonstrated for the pharmacokinetic parameters of IFN-alpha, which showed higher clearance for injections given at 9:00 PM than for those at 9:00 AM (P <.05). The metabolism of IFN-alpha was significantly higher in kidney obtained at 9:00 PM than at 9:00 AM (P <.05). These findings support that choosing the most appropriate time of day for administration of IFN-alpha, associated with the rhythmicity of IFN-alpha receptor function and IFN-alpha pharmacokinetics, may increase the antiviral activity in experimental and clinical situations.

2',5'-Oligoadenylate Synthetase↗

Treatment of human metastatic transitional cell carcinoma of the bladder in a murine model with the anti-vascular endothelial growth factor receptor monoclonal antibody DC101 and paclitaxel.

Vascular endothelial cell growth factor (VEGF) regulates angiogenesis and metastasis of bladder cancer (transitional cell carcinoma, TCC) through binding to VEGF receptor-2 (VEGFR-2). In this study, we evaluated whether the anti-VEGFR monoclonal antibody (Mab) DC101 in combination with paclitaxel inhibited tumorigenesis, angiogenesis, and metastasis of human TCC growing within the bladder of athymic nude mice. In vivo therapy with Mab DC101 and paclitaxel induced significant regression of bladder tumors compared with either agent alone. Median bladder weights were reduced from 601 mg in untreated controls, 422 mg in mice treated with paclitaxel alone (P < 0.005), 361 mg in mice treated with DC101 alone (P < 0.005), and 113 mg in mice that received combination therapy (P < 0.0005). Only one of nine mice developed spontaneous lymph node metastasis after combined treatment, compared with seven of seven untreated controls (P < 0.0005), six of eight after DC101 (P < 0.01), and five of eight mice after paclitaxel (P < 0.05). Combined treatment with both paclitaxel and DC101 inhibited tumor-induced neovascularity compared with all other groups (P < 0.005), without altering the expression of VEGF or flk1. Mab DC101 and paclitaxel combined enhanced apoptosis in the tumor and endothelial cells compared with other treatment (P < 0.005). These studies indicate that Mab DC101, which blocks VEGFR-2 function, has significant efficacy against human TCC, especially when combined with the chemotherapeutic agent paclitaxel. The antitumor effect was mediated by inhibition of angiogenesis and induction of both tumor cell and endothelial cell apoptosis.

Angiogenesis Inhibitors↗

[Study of appropriate surveillance of health appraisal for communities].

A study to determine the appropriate surveillance of health appraisal for communities was made using individual data for deaths in 1992-1996 in Maniwa County (population 51,000), individual data of medical examinations from 1995 to 1997 in Maniwa and other county (population 24,000), rate for people receiving medical examinations from 1983 to 1996 in Maniwa County and life table data for Japanese males in 1995. The results obtained were as follows: (1) The total YPLL (Years of Potential Life Lost) rate was reversely correlated with the proportion of people who had a medical examination as compared to the total population, with a time lag of about 6 years (P < 0.05). It can be concluded that past health appraisal may influence future indicators of death with a time lag of about 6 years. (2) In the case of calculation of Years of Potential Life Lost rate (YPLL rate = sum of ¿target age - (death age + 0.5) between n1 and n2 ages¿/population), if the target age is close to the n2, the number of deaths close to the n2 have a possibility of very small evaluation to influence of number of these near to n1. Therefore a target age must be set up some years above n2. (3) There is a peak point (about 90 years) among 0 and 99 years old for the YPLL rate in life tables for Japanese males in 1995 using the target age of 100. On the other hand, using a target age of 120 there was a linear increasing from about 75 age with no peak. Then, if YPLL rate with a target age of 100 is used, there may be big different values among n2 before peak age and after peak age. (4) To perform appropriate surveillance of health appraisal for communities (population size: 1000-2000), two indicators must be used. One is a simple rate for number of death peoples of some diseases to total population or of peoples who have an abnormal indicator on some medical examinations to total number of peoples who have a medical examination, in which case that person's age is not be considered. The other is Age-Adjusted YPLL or YPHL (Years of Potential Health Lost) rate not using a data of standard population that have been showed next equation. A target age should be set at 120, as a maximum age of human life rather than 80 or 100. Age - Adjusted T(n1 - n2) YPLL rate(by Inoue) [formula: see text] T: A target age (value of 120 is appropriate), n1: youngest individual age, n2: oldest age, i; individual age between n1 and n2, pi: population (in the case of YPHL rate, it shows a number of peoples receiving medical examination) at age of i, Qi: number of death on some disease (number of peoples who have an abnormal indicator on some item of medical examination) at age of i.

Adult↗

[A case of mediastinal pseudocyst with unusual cystic findings in computed tomography].

We report here a case of mediastinal pseudocyst with unusual CT findings. A 25-year-old woman was admitted to our hospital due to a chest abnormal shadow. She had a cystic mass which was located at anterior mediastinum and was adjacent to great vessels broadly without invasive findings. The intraoperative and histological findings revealed that the cystic mass was a pseudocyst which had been generated by the rupture of a thymic cyst to the mediastinum.

Adult↗

ATPase and GTPase activities copurifying with GTP-binding proteins in E. coli.

Intrinsic GTPase activity of GTP-binding proteins plays the vital role in regulating the downstream activation pathway. We examined the GTP and ATP hydrolyzing (NTPase) abilities of various bacterial and human GTP-binding proteins under different metabolic conditions. Two metabolic components, acetate and 3-phosphoglyceric acid (3-PG), have shown significant stimulatory action on NTPase activity of G-protein preparations. Acetyl phosphate and 2,3-bisphosphoglyceric acid (2,3-BPG) blocked these stimulations. From gel filtration analyses, we have determined two fractions containing metabolite-inducible NTPase activities which are independent of GTP-binding protein enzymatic actions. Therefore, one should be cautious when NTPase activity is examined in a buffer containing acetate often used for NTPase assay.

Acetates↗

[Treatment of lung cancer--state of the art in 2000].

Small-cell lung cancer (SCLC) is, in general, sensitive to anti-cancer chemotherapy and radiotherapy. Standard therapies for extensive SCLC are combination chemotherapies with cyclophosphamide, adriamycin and vincristine (CAV), with cisplatin and etoposide (PE), as well as an alternating CAV/PE program. On the other hand, the standard therapy for limited SCLC is chemoradiotherapy, especially PE and concurrent accelerated hyperfractionated radiotherapy. Based on the therapy, the current state of treatment of small cell lung disease is a median survival time of 10 months and a 3-year survival in 10% of patients with extensive disease, and a median survival time of 30 months and a 3-year survival in 30% of patients with limited disease. Promising trials under investigation including those for dose-intensive chemotherapy, multimodality treatment and combination chemotherapy adopting new drugs are introduced. The standard therapy for inoperable stage III non-small cell lung cancer is a multimodality therapy employing chemotherapy and radiotherapy. However, neither the timing of the radiotherapy nor the optimal combination of anti-cancer agents has yet been established. Nowadays, the combination of cisplatin-based chemotherapy and radiotherapy is expected to bring a median survival time of 15 months and a 3-year survival in 25% of patients. For stage IV non-small cell lung cancer, chemotherapy prolongs survival time by a modest but statistically significant amount of time. For the treatment of inoperable lung cancer, the survival benefit from the use of newly developed drugs with or without platinum is under investigation.

Antineoplastic Combined Chemotherapy Protocols↗

[Bacterial infection in the conjunctiva of patients with adenoviral conjunctivitis].

PURPOSE: We evaluate the microbiological features of mixed infection in adenovirus-infected conjunctiva. SUBJECTS: Isolation of bacteria was performed in 82 samples of adenoviral conjunctivitis at six eye clinics in Japan. METHODS: For microbiological diagnosis, we performed immunochromatography (IC) and polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP) analysis for detection and serotyping of adenovirus, and PCR for detection of herpes simplex virus (HSV) and Chlamydia trachomatis antigens out of 82 samples with adenoviral conjunctivitis. RESULTS: Pathogenic bacteria were isolated in 6 samples out of 82. Out of these 6 cases, 5 samples were gram-negative rods and most of them were Flavobacterium meningosepticum (4 samples). Adenovirus type 8 was isolated from all these mixed infection cases. However, HSV-1 and Chlamydia trachomatis were not found. CONCLUSIONS: From these results, it is suggested that gram-negative rods, especially F. meningosepticum, are the most common bacteria causing mixed bacterial infection in adenoviral conjunctivitis.

Adenovirus Infections, Human↗

Effects of the Japanese herbal medicine 'Inchinko-to' (TJ-135) on concanavalin A-induced hepatitis in mice.

Inchinko-to (TJ-135) is a herbal medicine consisting of three kinds of crude drugs, and in Japan it is administered mainly to patients with cholestasis. The present study evaluated the effects of TJ-135 on concanavalin A (con A)-induced hepatitis in mice in vivo and con A-induced cytokine production in vitro. When mice were pretreated with oral TJ-135 for 1 week before intravenous con A injection, the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly decreased 8 h after con A administration (-82%, -96% and -66% respectively). In histological investigations, sub-massive hepatic necrosis accompanying inflammatory cell infiltration was not observed in mice pretreated with TJ-135. Serum levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and IL-2 were significantly lower in mice pretreated with TJ-135 compared with controls, while IL-10 levels were higher in these mice. Intrasplenic IL-12 levels were significantly lower in mice pretreated with TJ-135, while intrasplenic IL-10 levels were higher in these mice. In vitro, IL-10 production by splenocytes was increased by the addition of TJ-135 to the culture medium, whereas the production of IL-12 and IFN-gamma was inhibited. These results suggest that con A-induced hepatitis was ameliorated by pretreatment with TJ-135. With regard to the mechanism of these effects of TJ-135, we speculate that TJ-135 inhibits the production of inflammatory cytokine and enhances the production of anti-inflammatory cytokines. Therefore administration of TJ-135 may be useful in patients with severe acute hepatitis accompanying cholestasis or in those with autoimmune hepatitis.

Alanine Transaminase↗

Did ossification of the posterior longitudinal ligament of the spine evolve in the modern period? A paleopathologic study of ancient human skeletons in Japan.

OBJECTIVE: To investigate the historical origins of ligamentous ossifications of the spine in Japan. METHODS: We studied skeletons of Jomonese of the period 5000-2300 years BP, of Japanese of the 17th-19th century Edo Period, and of Ainu of the 18th-20th century in Japan with special emphasis on spinal ligament ossifications as in the posterior longitudinal ligament. A comparison to our previous study on ancient Chinese skeletons was done. RESULTS: Cervical ossification of the posterior longitudinal ligament (OPLL) was the only ossification that increased significantly in prevalence in people of the near-modern period in comparison to the Neolithic gathering-hunting people. CONCLUSION: Socioeconomic changes from a subsistence gathering-hunting economy to the near-modern livelihood depending on rice-eating and a diet high in vegetable protein are speculated to be responsible for the prevalence increase of cervical OPLL.

Adult↗

Gene therapy of human bladder cancer with adenovirus-mediated antisense basic fibroblast growth factor.

We previously investigated the role of basic fibroblast growth factor (bFGF) as a mediator of angiogenesis, tumorigenicity, and metastasis of transitional cell carcinoma (TCC) of the bladder. In the present study, we determined whether adenoviral-mediated antisense bFGF gene transfer therapy (Ad bFGF-AS) would inhibit TCCs growing in the subcutis of nude mice. In vitro, Ad bFGF-AS inhibited endothelial cell proliferation and enhanced apoptosis. The highly metastatic human TCC cell line 253J-BV(R) was implanted ectopically in the subcutis of athymic nude mice, and therapy was begun when the tumors reached a diameter between 5 and 7 mm. Intralesional therapy with Ad bFGF-AS decreased the in vivo expression of bFGF and matrix metalloproteinase type 9 mRNA and protein, and reduced microvessel density and enhanced endothelial cell apoptosis. Tumor growth was significantly inhibited by Ad bFGF-AS (mean, 58 mg) compared with controls [saline (mean, 562 mg), beta-galactosidase adenovirus (mean, 586 mg), and sense bFGF adenoviral therapy (Ad bFGF-S; mean, 3012 mg)]. These results suggest that Ad bFGF-AS therapy affects endothelial cells directly and tumor cells indirectly through down-regulation of bFGF and matrix metalloproteinase type 9, resulting in endothelial cell apoptosis and significant tumor growth inhibition. Furthermore, these studies confirm that bFGF expression is a valid target for the therapy of bladder cancer.

Adenoviridae↗

The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy.

To determine the prognostic value of angiogenesis factor expression for patients with muscle-invasive transitional cell carcinoma (TCC) of the bladder treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy and radical cystectomy, we evaluated the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8) by in situ hybridization, and we determined microvessel density (MVD) by immunohistochemistry. These factors were evaluated in 55 biopsy specimens prior to therapy and in the cystectomy specimens of 51 patients after completion of therapy. By univariate analysis, VEGF expression and MVD in the biopsy specimens were significant predictors of disease recurrence. By multivariate analysis, only VEGF expression was an independent prognostic factor. Pathological stage, bFGF expression, and MVD in the cystectomy specimens after therapy were all independent prognostic factors for disease recurrence. The results of this exploratory study indicate that the expression levels of VEGF and bFGF as indicated by in situ hybridization and MVD as indicated by immunohistochemistry identify patients with muscle-invasive TCC who are at high risk of developing metastasis after aggressive therapy with systemic M-VAC chemotherapy and radical cystectomy.

Adult↗

Paclitaxel enhances the effects of the anti-epidermal growth factor receptor monoclonal antibody ImClone C225 in mice with metastatic human bladder transitional cell carcinoma.

Previously we reported that when cells from the human transitional cell carcinoma cell line 253J B-V growing orthotopically within the bladder of athymic nude mice were treated with the anti-epidermal growth factor receptor monoclonal antibody C225, angiogenesis was inhibited, resulting in regression of the primary tumor and inhibition of metastasis. In this study, we evaluated whether paclitaxel enhanced this therapeutic effect of C225. In vitro, the proliferation of 253J B-V cells was inhibited more by the combination of C225 and paclitaxel than with either agent alone. In vivo therapy with C225 and paclitaxel resulted in significantly greater regression of tumors compared with either agent alone. Median bladder tumor weight was 85 mg (range, 69-133 mg) compared with 168 mg (range, 72-288 mg) after C225 alone (P < 0.05), and 273 mg (range, 83-563 mg) after paclitaxel alone (P < 0.005). The incidence of spontaneous lymph node metastasis was also reduced by the combination of C225 with paclitaxel, although this result did not significantly differ from results after the use of C225 alone. Treatment with paclitaxel and C225 down-regulated the expression of basic fibroblast growth factor, vascular endothelial cell growth factor, interleukin-8, and matrix metalloproteinase type 9 and inhibited tumor-induced neovascularity compared with untreated controls (P < 0.005). Moreover, the combination of C225 and paclitaxel enhanced apoptosis in tumor and endothelial cells compared with either agent alone (P < 0.005). These studies indicate that therapy with paclitaxel increases the ability of C225 to inhibit tumorigenicity and metastasis. This effect is mediated by inhibition of angiogenesis and induction of apoptosis.

Animals↗

Hyperplasia of the thymic gland in a patient with Graves' disease.

A tumor-like lesion in the anterior mediastinum was recognized in a 21-year-old female patient with Graves' disease. A CT examination and MRI suggested a thymoma. A subtotal thyroidectomy and a total thymectomy were therefore performed simultaneously. A pathological study of the thymic mass showed thymic hyperplasia. These findings suggest that an enlarged anterior mediastinal mass in a Graves' disease could thus sometimes turn out to be thymic hyperplasia and not a thymoma.

Adult↗

[Polymyositis with marked paravertebral muscle atrophy in patients with primary biliary cirrhosis].

We reported two patients with polymyositis (PM) associated with primary biliary cirrhosis (PBC) who noticed head-drop as the incipient symptom. Muscle computed tomography showed marked hypodensity in the paravertebral muscles as compared with limb muscles. Patient 1, a 48-year-old female, was admitted in our hospital for the examination because of her neck and proximal limb muscle weakness, increasing fatigability, and abnormal serum liver and muscle enzyme levels. She felt her throat was so dry at age 39, and she noticed weight loss at age 41 and head-drop at age 42. A diagnosis of PM was made from symmetrical proximal limb muscle weakness, elevated creatine kinase (CK) level, and the electromyographic and muscle biopsy findings. Her illness was also diagnosed as PBC because of the increased serum alkaline phosphatase and IgM immunoglobulin levels, and liver biopsy findings. The anticentromere antibody titer was positive, though the antimitochondrial antibody titer negative. The HLA typing was DR 4, DR 8, DR53, DQ 4, DQ 6, DRB 1 (0405/0803). She was placed on 60 mg of prednisolone/day for PM and 300 mg of ursodeoxycholic acid/day for PBC. Patient 2, a 49-year-old female, presented with proximal limb muscle weakness and head-drop. Serum CK, alkaline phosphatase and IgM immunoglobulin levels were increased. The antimitochondrial antibody titer was positive. She began to have 60 mg of prednisolone/day, and 50 mg of azatioprine/day and 300 mg of ursodeoxycholic acid/day were subsequently added. PM associated with PBC seems to be rare, because only 21 cases have been described in literature. In those patients, marked paravertebral muscle atrophy has never been described. Further study is necessary to examine whether or not the preferential paravertebral muscle involvement is a striking and diagnostic finding for PM with PBC.

Atrophy↗