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Biomedical subjects

M Mochizuki

Publications and source records attributed to M Mochizuki.

At least 217 records · Page 12Linked to original sources

Inhibition of tumor-induced angiogenesis by a synthetic lipid A analogue with low endotoxicity, DT-5461.

We investigated the effect of a synthetic lipid A analogue with low endotoxicity, DT-5461, on the neovascularization induced by B16-BL6 melanoma in syngeneic mice. A systemic single administration of DT-5461 caused a marked decrease in the number of vessels oriented toward the tumor mass and in the tumor size during the early phase of vasculogenesis (on day 4 after tumor inoculation), with little or no inhibition in the following phases. Multiple i.v. administrations of DT-5461 at intervals of 4 days (an effective schedule for inhibiting tumor metastasis) significantly reduced the number of capillary vessels and tumor growth over a period of 14 days after the tumor implantation. Multiple systemic administrations of DT-5461 on days 1, 5 and 9 after tumor inoculation caused a high production of endogenous tumor necrosis factor-alpha (TNF-alpha) in tumor sites although this treatment modality induced a low production in serum of tumor-bearing mice. Tumor homogenate from mice treated with DT-5461 suppressed the proliferation of endothelium in vitro, whereas sera from animals given DT-5461 had little effect. Furthermore, the antiproliferative effect of the tumor homogenate from mice treated with DT-5461, was completely abrogated by anti-mTNF-alpha monoclonal antibody (mAb). The anti-angiogenic effect of DT-5461 was also completely abrogated by rabbit anti-mouse tumor necrosis factor-alpha (anti-mTNF-alpha) antiserum, whereas the inhibition of tumor growth by DT-5461 was only slightly diminished. Tumor homogenate from mice treated with DT-5461 suppressed the proliferation of endothelium in vitro, whereas sera from animals given DT-5461 had little effect. Furthermore, the antiproliferative effect of the tumor homogenate from mice treated with DT-5461 was completely neutralized by anti-mTNF-alpha mAb. Multiple i.v. administrations of DT-5461 after s.c. implantation of B16-BL6 cells significantly inhibited the growth of primary tumors measured at the time of tumor excision on day 21, and the lung metastasis of melanoma cells as compared with the untreated control in the spontaneous metastasis model. These results suggested that the suppressive effect upon tumor-associated angiogenesis by DT-5461 contributes in part to the inhibition of tumor metastasis.

Amino Acid Sequence↗

Spontaneous production of various cytokines except IL-4 from CD4+ T cells in the affected organs of sarcoidosis patients.

We investigated surface antigens and spontaneous cytokine production of T cells from bronchoalveolar lavage fluid (BALF) and aqueous humor (AH) from pulmonary sarcoidosis patients for a better understanding of the role of T cells in granuloma formation. The levels of CD3, CD11b, and CD28 antigen expression on freshly isolated T cells in the BALF of patients were significantly lower than those in peripheral blood lymphocytes (PBL) of either sarcoidosis patients or healthy donors (HD). In contrast, the levels of CD80 (B7/B7-1) and CD86 (B70/B7-2) antigen expression were significantly higher on these T cells and alveolar macrophages in the BALF of patients. Fifty-three T cell clones (TCC) established from the BALF and AH of the three sarcoidosis patients displayed primarily either CD4+ CD11b+ CD28+ or CD4+ CD11b- CD28- phenotypes. Most (61-90%) of these TCC spontaneously produced greater amounts of IL-1 alpha, IL-10, tumour necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) than did TCC from the PBL from sarcoidosis patients or HD (P < 0.05). Interferon-gamma (IFN-gamma), IL-6, and IL-2, but not IL-4, were also produced by 40-48% of these TCC. These results suggest that CD4+ T cells of the affected organs of sarcoidosis patients are activated and involved in the immunopathogenesis of sarcoidosis through production of various cytokines.

Adult↗

Intracranial meningioma masquerading as a primary pleuropulmonary tumor.

Extracranial metastasis was found in an intracranial meningioma with low proliferative potential before the detection of the primary tumor. Pleuropulmonary tumors were incidentally detected on chest X-ray in an asymptomatic 25 year old female. Excised tumors of the right pleura and lung showed histological features similar to meningotheliomatous meningioma, which led to the discovery and excision of the intracranial tumor. Both tumors showed the same histologic pattern: meningotheliomatous meningioma with low mitotic activity. The proliferative component, determined by the monoclonal antibody Ki-67, was further evaluated in the primary tumor and the metastases of the present case, as well as in 12 other intracranial meningiomas. Ki-67 positive ratios at the primary and metastatic sites of the present cases were 1.2 and 1.1%, respectively, which is as low as other benign meningiomas, and this suggests that factors other than the proliferative potential is responsible for extracranial metastasis of meningioma.

Adult↗

Enhanced magnetic resonance imaging in monitoring of conservative treatment of cervical pregnancy.

We report on case of cervical pregnancy successfully treated by two 5-day courses of etoposide, embryocide with the injection of KCl, the injection of methotrexate into the placenta, and cervical curettage. We evaluated the effects of these treatments by measuring urinary human chorionic gonadotropin (hCG) titers and serial hCG beta-carboxy-terminal peptide (CTP) levels. Moreover, we used ultrasonography and magnetic resonance imaging (MRI) enhanced by gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) to diagnose and to evaluate the blood supply to the trophoblast. The beneficial outcomes suggest that Gd-DTPA-enhanced MRI is useful in detecting the blood supply to the trophoblast, in order to avoid the massive bleeding that results from conservation treatments. This is the first report of the usefulness of Gd-DTPA-enhanced MRI for the successful conservative treatment of cervical pregnancy.

Adult↗

Inducible expression of a gene encoding an L41 ribosomal protein responsible for the cycloheximide-resistant phenotype in the yeast Candida maltosa.

In a previous paper (S. Kawai, S. Murao, M. Mochizuki, I. Shibuya, K. Yano, and M. Takagi, J. Bacteriol. 174:254-262, 1992), we showed that in each genome of several yeast species, there is one of two types of L41 gene, one for an L41 (Q-type) protein which confers cycloheximide (CYH) resistance or one for an L41 (P-type) protein which does not. These genes have been suggested to be responsible for the CYH response used in taxonomy. For example, Saccharomyces cerevisiae, which is CYH sensitive, has a P-type L41 gene, while Kluyveromyces fragilis and Candida maltosa, which are CYH resistant, have Q-type L41 genes. However, in contrast to K. fragilis, which is constitutively resistant to CYH, C. maltosa is inducibly resistant to CYH. Here, we show that C. maltosa has both types of the L41 gene in its genome and that expression of the Q-type L41 gene is induced by CYH while the P-type L41 gene is constitutively expressed.

Base Sequence↗

Increased number of circulating HTLV-1 infected cells in peripheral blood mononuclear cells of HTLV-1 uveitis patients: a quantitative polymerase chain reaction study.

AIMS: This study aimed to characterise the status of viral infection in patients with HTLV-1 uveitis (HU) by quantifying the circulating HTLV-1 infected cells in the peripheral blood. METHODS: Genomic DNA samples of peripheral blood mononuclear cells (PBMC) were obtained from 25 patients with HU, 14 patients with tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM), and 21 asymptomatic carriers of HTLV-1. Quantitative polymerase chain reaction (PCR) of the gag region of HTLV-1 provirus DNA was performed on these DNA samples. To confirm the PCR, genomic Southern blot hybridisation was performed to identify integrated HTLV-1 provirus. This procedure detected a few percent of HTLV-1 infected cells in the PBMC. RESULTS: Most of the HU patients had a significantly increased number of circulating HTLV-1 infected cells (mean (SD) 3.84% (4.45%) of the PBMC), whereas the percentage of infected cells in most asymptomatic carriers was less than 1% (0.54% (1.11%)). Most of the TSP/HAM patients also had a relatively high percentage (11.63% (7.67%)). The differences among these three groups were highly significant by the Mann-Whitney U test. CONCLUSION: The results suggested that the increase in the number of HTLV-1 infected cells is one base for the development of inflammatory HU lesions, as it is for TSP/HAM.

Adult↗

Immunopathological mechanisms of human T cell lymphotropic virus type 1 (HTLV-I) uveitis. Detection of HTLV-I-infected T cells in the eye and their constitutive cytokine production.

The immunopathology of human T cell lymphotropic virus type 1 (HTLV-I) uveitis was addressed by using T cell clones (TCC) established from the intraocular fluid of patients with HTLV-I uveitis. Proviral DNA of HTLV-I was identified in 55 out of 94 (59%) or 13 out of 36 (36%) TCC from the ocular fluid or the peripheral blood of these patients, respectively. Most of HTLV-I-infected TCC had a CD3+ CD4+ CD8- phenotype. HTLV-I infection on TCC was confirmed by analysis of the viral mRNA, nucleotide sequence, virus-associated proteins, and virus particles. HTLV-I-infected TCC, but not HTLV-I negative TCC, constitutively produced high amounts of IL-6 (1,336 +/- 1,050 pg/ml) and TNF-alpha (289 +/- 237 pg/ml) in the absence of any stimuli. HTLV-I-infected TCC from the ocular lesion also constitutively produced high amounts of IL-1 alpha (12,699 pg/ml), IL-2 (61 pg/ml), IL-3 (428 pg/ml), IL-8 (1,268 pg/ml), IL-10 (28 pg/ml), IFN-gamma (5,095 pg/ml), and GM-CSF (2,886 pg/ml). Hydrocortisone, a drug effective in vivo for the treatment of HTLV-I uveitis, severely depressed cytokine production in vitro in most cases. In summary, the results demonstrated direct evidence of HTLV-I infection of the eye and suggest that cytokines produced by HTLV-I-infected T cells are responsible for the intraocular inflammation in patients with HTLV-I uveitis.

Adult↗

Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng.

We examined the inhibitory effect of two saponin preparations from Red ginseng, 20(R)- and 20(S)-ginsenoside-Rg3, in comparison with that of ginsenoside-Rb2, on lung metastasis produced by two highly metastatic tumor cells, B16-BL6 melanoma and colon 26-M3.1 carcinoma, in syngeneic mice. In an in vitro analysis, both saponin preparations showed a significant inhibition of adhesion to fibronectin (FN) and laminin (LM) by B16-BL6 melanoma. Similarly, they significantly inhibited the invasion of B16-BL6 cells into the reconstituted basement membrane (Matrigel)/FN in a dose-dependent manner. In an experimental metastasis model using B16-BL6 melanoma, consecutive intravenous (i.v.) administrations of 100 micrograms/mouse of 20(R)- or 20(S)-ginsenoside-Rg3 1, 2, 3 and 4 d after tumor inoculation led to a significant decrease in lung metastasis. The inhibitory effect of i.v. administration of both ginseng saponins on the tumor metastasis of B16-BL6 melanoma was also recognized in a low dose of 10 micrograms/mouse. The oral administration (p.o.) of both saponins (100-1000 micrograms/mouse) induced a significant decrease in lung metastasis of B16-BL6 melanoma. Moreover, both ginseng saponins were effective in inhibiting of lung metastasis produced by colon 26-M3.1 carcinoma. When 20(R)- or 20(S)-ginsenoside-Rg3 was orally administered consecutively after tumor inoculation in a spontaneous metastasis model using B16-BL6 melanoma, both of them significantly inhibited lung metastasis. In the experiment involving neovasculization by tumor cells in vivo, both mice groups given each saponin preparation after tumor inoculation exhibited a significant decrease in the number of blood vessels oriented toward the tumor mass, with no repression of tumor size. These findings suggest that both ginseng saponins, 20(R)- and 20(S)-ginsenoside-Rg3, possess an ability to inhibit the lung metastasis of tumor cells, and the mechanism of their antimetastatic effect is related to inhibition of the adhesion and invasion of tumor cells, and also to anti-angiogenesis activity.

Animals↗

Activation of N-nitrosodialkylamines to mutagens by a metalloporphyrin/oxidant model system for cytochrome P450.

N-Nitrosodialkylamines are environmental alkylating carcinogens which are metabolically activated to alpha-hydroxy nitrosamines by cytochrome P450. The precise mechanism of their activation is not well understood, and a simplified chemical model for cytochrome P450 as a non-enzymatic system is useful for investigating the mechanism. In the present study, a chemical model was used in a bacterial mutation assay as a substitute of S9 mix, and its ability in the activation of N-nitrosodialkylamines was elucidated. In the presence of tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride and tert-butyl hydroperoxide, the mutagenicity of N-nitrosodialkylamines [alkyl = methyl (NDM), ethyl (NDE), propyl (NDP) and butyl (NDB)] in Salmonella typhimurium YG7108 was detected. The mutagenicity increased by the pre-incubation and was dependent on the concentration of mutagens. The mutagenic activity of N-nitrosodialkylamines in Salmonella typhimurium YG7108 was in the following order: NDB > NDM > NDE approximately NDP. The formation of aldehydes derived from dealkylation in the present model was exemplified by the formation of acetaldehyde from NDE. These results showed that N-nitrosodialkylamines were activated by the model system, and consequent mutagenicity was observed. The oxidation by the model can mimic the metabolic activation of chemical carcinogens by cytochrome P450, and the biomimetic catalyst is useful in investigating the mechanisms of the metabolic pathway of N-nitrosodialkylamines.

Acetaldehyde↗

Dealkylation of N-nitrosodibenzylamine by metalloporphyrin/oxidant model systems for cytochrome P450.

N-Nitrosodialkylamines are alkylating carcinogens which are metabolically activated to alpha-hydroxy nitrosamines through oxidative dealkylation by cytochrome P450. In this study, the dealkylation step in the activation of N-nitrosodibenzylamine (NDBz) was investigated with metalloporphyrin/oxidant model systems under non-aqueous conditions, as biomimetic chemical models of cytochrome P450. In the model systems, NDBz was dealkylated and benzaldehyde was released. The catalytic activity required a porphyrin ring with a central metal that can interact with an oxidant. The oxidative activity of the model varied with the oxidant used in the order of tert-butyl hydroperoxide > cumene hydroperoxide > iodosobenzene, and also with the central metal of porphyrin used in the order of tetraphenylporphyrinatoiron(III) chloride > its manganese derivative. It was confirmed that N-nitrosodialkylamine undergoes oxidation to alpha-hydroxy nitrosamine in chemical model systems which are free of protein. These biomimetic models should be useful in elucidating the mechanisms of the metabolism of N-nitrosodialkylamines.

Benzaldehydes↗

[Differential patterns of the number and proportion of blood leukocytes following endurance exercise of moderate, strenuous and severe conditions].

A study was conducted to elucidate the acute effects of endurance exercise on white blood cells by setting three conditions of different intensity and duration; (a) an upper limit of aerobic exercise for health promotion and (b) superior limits within endurance exercise tolerance for untrained persons were prescribed separately for the same healthy untrained male student volunteers (n = 10) at intensities of 85% and 95% of the individual anaerobic threshold (AT) values for 1 h and 1.5 h, respectively, on a bicycle ergometer. In addition, (c) participants in a 100-km marathon race (n = 20) who continued running for 10-13 h were examined. Every condition caused significant leukocytosis due to predominant neutrophilia and, to a minor degree, a significant increase in monocyte number, the magnitude of which depended on the severity of endurance workload and persisted even 1 h after the termination of exercise. Simultaneously, microscopic evaluation of blood smears revealed the occurrence of an increased proportion of band neutrophils and a decreased proportion of hypersegmented neutrophils (shift to the left) following exercise in condition (b) but not in (a), suggesting that neutrophils are mobilized partly from the bone marrow reserve to the circulation. On the other hand, peripheral lymphopenia was observed after the termination of endurance exercise. These phenomena closely mimicked the known effects of exogenous glucocorticoid administration, suggesting an association with endogenous stress hormone (cortisol) secretion following strenuous exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Rapid inhalation induction of anesthesia by halothane, enflurane, isoflurane and sevoflurane and their cardiopulmonary effects in dogs.

The rapid inhalation induction of anesthesia (RII) by mask inhalation of halothane, enflurane, isoflurane and sevoflurane at an equianesthetic concentration (2.5 MAC) was evaluated in 24 beagle dogs. The differences in movements, induction and intubation time between anesthetics were mainly associated with the differences in each blood/gas solubility. The most rapid and smoothest induction was observed by sevoflurane inhalation (209.0 +/- 44.2 sec), followed by isoflurane inhalation (285.8 +/- 34.1 sec). Halothane inhalation took the longest induction time (790.3 +/- 75.7 sec). Movements during RII were minimal in sevoflurane group comparing to the other groups. Heart rate, cardiac output and rate pressure product significantly increased after the beginning of inhalation in all the dogs except for those of halothane group. These changes exceeded the physiological level just after the beginning of inhalation, however, rapidly reversed to the maintenance level (1.5 MAC) approximately 10 min after intubation. Consequently, sevoflurane seemed to be the best inhalational anesthetic for RII in dogs without significant problems in respiratory and/or cardiac functions. Isoflurane also induced rapid induction with some degree of the movements.

Analysis of Variance↗

Clinical application of rapid inhalation induction of anesthesia using isoflurane and sevoflurane with nitrous oxide in dogs.

Clinical usefulness of rapid inhalation induction of anesthesia (RII) using 5.0 vol.% isoflurane (GOI) and sevoflurane (GOS) with N2O was evaluated in 124 canine patients. Induction times, loss of various reflexes and movement times were significantly faster in GOI group than in GOS group. Scores for the easiness of intubation and the degree of movements were also significantly less in GOI group than in GOS group. Positive correlation between body weight and degree of movements was observed in both induction groups. Thus, RII using GOI is a practically useful and safe induction modality in small- to medium-sized dogs.

Age Factors↗

Establishment of carrier-state infection of a feline renal cell line with feline syncytial virus.

Although feline syncytial virus (FSV) is normally highly cytopathogenic in Crandell feline kidney cells, a non-cytopathic persistent infection was established in the cells after cocultivation of the initially infected cells with uninfected cells 4 times. More than 90% of the persistently infected cells were positive for FSV antigen, and electron microscopy showed that the culture produced morphologically normal FSV. Virus from the carrier culture was infectious, however, the titer of the virus from the culture was lower than that from the cytocidally infected CRFK cells.

Animals↗

Immunohistochemical evidence for the presence of tumor necrosis factor-alpha in the infant and adult human ovary.

The cytologic localization and cellular levels of tumor necrosis factor-alpha (TNF alpha) in the human ovary during follicular growth and regression were examined by the avidin/biotin immunoperoxidase method with a specific antibody to human recombinant TNF alpha. In the infant ovary, TNF alpha immunostaining was present only in the oocyte within the primordial follicles. TNF alpha immunostaining was also present within the oocyte in primordial follicles of the adult ovary. Positive immunostaining for TNF alpha in granulosa cells became apparent in preantral follicles, while that in theca interna cells began to appear at the antral follicle stage. The staining intensity of the oocyte increased as the oocyte reached the preovulatory stage. The intensity of immunostaining for TNF alpha in the granulosa and thecal cells increased as the follicle became larger and matured. In corpora lutea, the immunostaining for TNF alpha persisted in the granulosa lutein and theca lutein cells and intensified in the mid luteal phase. In the regressing corpora lutea, TNF alpha immunostaining in the luteal cells decreased as the regression advanced. Regressed corpora lutea with a central core of scar tissue were bordered by macrophage-like cells which exhibited intense immunostaining for TNF alpha. In the cortex region, the corpus albicans was negative for TNF alpha immunostaining, whereas macrophage-like cells peripheral to the corpus albicans exhibited intense immunostaining for TNF alpha. In the medullary region, the corpus albicans and surrounding stromal cells were totally negative for TNF alpha. By contrast, in the early atretic stage, the degenerating oocyte showed weak immunostaining for TNF alpha, while the granulosa and theca interna cells showed moderate immunostaining for TNF alpha. In the late atretic stage, the immunostaining for TNF alpha in the scattered granulosa cells became negligible, whereas the theca interna cells showed intense immunostaining for TNF alpha. The results obtained indicate that the oocyte is the primary intrafollicular site of TNF alpha localization within the ovary and that TNF alpha may participate in regulating follicular growth, regression and atresia.

Adult↗

Mitochondrial encephalomyopathy with A to G transition of mitochondrial transfer RNA(Leu(UUR)) 3,243 presenting hypertrophic cardiomyopathy.

In a 24-year-old woman with mitochondrial encephalomyopathy presenting hypertrophic cardiomyopathy, microscopical examination of myocardial biopsy specimen disclosed severe vacuolar degeneration of myocardium and aggregates of enlarged mitochondria with proliferated cristae. Limb muscle biopsy specimen showed "ragged-red fibers" light microscopically and enlarged abnormal mitochondria with markedly increased cristae ultrastructurally. Mitochondrial DNA analysis by polymerase chain reaction (PCR) revealed an A-to-G transition in the mitochondrial transfer RNA(Leu)(UUR) gene at nucleotide position 3,243 which is reported to be associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). However, the clinical features of this case, presenting mainly cardiac abnormalities, were not consistent with the typical MELAS.

Adult↗

Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat.

FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.

Administration, Topical↗

[Effects of estrogen and thyroid hormone on EGF receptor expression, proliferative activity and SCC production in the CaSki cervical carcinoma cells].

This study was undertaken to see if estrogen and thyroid hormone affected EGF-receptor (EGF-R) expression, proliferative activity and intracellular SCC levels in uterine cervical squamous carcinoma cells. The uterine cervical cancer cell line (CaSki) was cultured in vitro in the absence or presence of 17 beta-estradiol (E2) or L-triiodothyronine (T3) in a serum free condition. Effects of E2 or T3 on the characteristics of EGF-R were assessed by the Scatchard analysis of the binding assay with 125I-EGF. Cellular levels of EGF-R expression were examined by the immunoperoxidase method with a monoclonal antibody to EGF-R. Proliferative activity of the cells was determined by proliferating cell nuclear antigen (PCNA) immunostaining, 3H-thymidine uptake and the number of cells. The effects of E2 or T3 on intracellular SCC levels were also examined by determining the intracellular SCC concentration with an SCC-RIA Kit. The scatchard analysis of 125I-EGF binding to CaSki cells showed that the addition of E2 or T3 had little effect on the affinity of EGF-R for CaSki cells but increased the capacity of EGF-R for the cells. Immunocytochemical staining with anti EGF-R antibody demonstrated that EGF-R expression in the CaSki cells was augmented by the addition of E2 or T3. The addition of E2 or T3 also resulted in an increase in 3H-thymidine uptake by the CaSki cells, the PCNA positive rate and the number of cells. Furthermore the addition of E2 or T3 increased intracellular SCC in the CaSki cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗