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Biomedical subjects

M Kabuto

Publications and source records attributed to M Kabuto.

At least 73 records · Page 4Linked to original sources

Production of tissue inhibitor of metalloproteinases-1 (TIMP-1) by human astrocytic tumors.

Production of tissue inhibitor of metalloproteinases-1 (TIMP-1), a specific inhibitor of matrix metalloproteinases, was investigated in human astrocytic tumors (n = 15) and normal brain tissues (n = 3). Enzyme immunoassay indicated that TIMP-1 levels in the culture media of tumor explants were significantly higher in glioblastomas as compared with anaplastic astrocytomas, astrocytomas, and normal brain tissues. Immunohistochemistry using a monoclonal antibody against TIMP-1 demonstrated that TIMP-1 was detectable mainly in tumor cells, especially in glioblastoma. These results suggest that increased expression of TIMP-1 is associated with the malignant progression of astrocytic tumors.

Adult↗

Selenium levels and glutathione peroxidase activities in blood in an andean high-altitude population.

Selenium (Se) levels in blood (whole blood, erythrocytes and serum) and blood glutathione peroxidase (GSH-Px) activity were investigated in people living at high altitude in Bolivia (4,000 m above sea level). These parameters were compared to those of people living at low altitude (300 m above sea level). The Se levels in whole blood of the high-altitude subjects did not differ significantly from those of the low-altitude subjects. However, the Se levels in erythrocytes were significantly lower in the high-altitude subjects than in the low-altitude subjects, whereas serum Se levels were higher in the high-altitude subjects than in the low-altitude subjects. GSH-Px activity (Unit/g Hb) was significantly lower in the high-altitude subjects than in the low-altitude subjects. The mean corpuscular Hb concentration (MCHC), an indicator of the age of erythrocytes, in the high-altitude subjects was significantly higher than in the low-altitude subjects. These results show that the GSH-Px activity in the blood of the high-altitude subjects is relatively low. This may be due to their aged erythrocytes and/or to relatively low Se intake in the high-altitude population compared with low-altitude population.

Adolescent↗

[Antitumor effect of MX2, a new morpholino anthracycline against C6 glioma cells and its combination effect with photodynamic therapy in vitro].

MX2, a new lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to adriamycin against murine and human tumor cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. Colony formation is inhibited even with only 2 hour treatment with MX2 in a dose-dependent manner. In this colony forming efficiency assay the drug concentration required for 50% inhibition of colony formation for C6 glioma cells was 24.0 +/- 4.5 ng/ml. Mild photocytotoxicity of MX2 against C6 glioma cells was observed at a high concentration (100 ng/ml) of MX2 following exposure to white light but not red light. In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) exhibited an additive cytotoxic effect against C6 glioma cells when the cells were treated with MX2 either immediately after red light illumination following incubation with HpD or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.

Animals↗

Clear cell (glycogen-rich) meningioma with special reference to spherical collagen deposits.

A detailed immunohistochemical and electron microscopic study of a case of clear cell (glycogen-rich) meningioma is presented. The neoplasm recurred three times and the patient died of the disease. The specimens obtained at all three operations showed similar basic histologic patterns. The tumor was comprised mainly of a syncytial, sheet-like proliferation of polygonal cells with clear cytoplasm containing abundant glycogen. The immunohistochemical features included epithelial membrane antigen- and vimentin-positive cytoplasm. The ultrastructural examination revealed distinctive meningocytic cells which contained large amounts of glycogen granules. In addition, the presence of numerous blocky, collagen conglomerations were a conspicuous feature of this tumor. The collagen deposits exhibited intensive immunopositivity for types I, III, IV and VI collagen, and their fine structure suggested the production of the extracellular matrix substance from the contiguous meningothelial cells with well developed Golgi complexes and frequent vesicles near the cell membrane. Proliferating cell nuclear antigen cell kinetics study revealed high labeling index of this neoplasm. The findings for this clear cell (glycogen-rich) meningioma may be useful in the differential diagnosis and treatment of this distinctive subtype of meningioma.

Adult↗

[Successful treatment with administration of systemic high dose methotrexate and intraarterial carboplatin for osteosarcoma of the skull: a case report].

An 11-year-old boy was admitted with a painless lump in the right frontal area as his chief complaint. On admission, physical and neurological examinations were normal except for the localized lump constituting the frontal lesion. Skull roentgenogram showed an osteoblastic and osteolytic mass with radiating bony spicules "sunray appearance" around the coronal suture. CT scans demonstrated it more clearly. The initial surgery was performed in July 1993. Pathological specimen showed osteosarcoma of the skull. The patient was transferred to our hospital for chemotherapy. The regimen consisted of intravenous high dose methotrexate 9,000 mg given for 6 hours with leucovorin rescue in a single course. Following 4 courses of high dose methotrexate, he underwent residual tumor resection. Two courses of intraarterial carboplatin 150 mg and methotrexate 200 mg were also given. Histologically, the lesion showed complete remission of the tumor, and no viable tumor cells were seen. Two additional courses of high dose methotrexate were given. The patient is doing well without evidence of recurrence. This case indicates that the chemotherapy with systemic high dose methotrexate and intraarterial carboplatin and methotrexate is effective for skull osteosarcoma.

Antineoplastic Combined Chemotherapy Protocols↗

Effect of mannitol on focal cerebral ischemia evaluated by magnetic resonance imaging.

We have evaluated the effect of mannitol on focal cerebral ischemia using T2-weighted magnetic resonance (MR) imaging and intravoxel incoherent motion (IVIM) MR imaging. The left middle cerebral artery (MCA) was exposed via the transorbital approach in 20 adult cats and occluded just proximal to the origin of the perforating arteries. Seven cats in treatment group received mannitol (0.5 g/kg i.v.) at 0, 6, 12 and 18 hours after MCA occlusion. The other 13 cats received saline and served as controls. Sequential MR coronal images were obtained at 2, 4, 6, and 24 hours after MCA occlusion using a GE Signa (1.5 tesla) system. IVIM MR imaging demonstrated ischemic cerebral injury as a sharply demarcated area at 2 hours after MCA occlusion in control group, while T2-weighted MR imaging failed to show clear evidence of the injury until 2-6 hours. At 24 hours after MCA occlusion, the infarcted area in the mannitol treatment group was 36.9 +/- 7.7% (S.E.M) of the left hemisphere, as compared to 57.3 +/- 5.3% in control group (p < 0.05). Mannitol has beneficial effect on ischemic injury.

Animals↗

Subcellular localization and cellular pharmacokinetics of MX2, a new morpholino anthracycline in glioma cells using confocal laser scanning microscopy.

The cellular uptake, subcellular distribution and retention of MX2, a new morpholino anthracycline, were compared with those of adriamycin (ADM) using confocal laser scanning microscopy (CLSM) in rat C6 and human T98G glioma cell lines. The tumor cells were exposed to 1-30 micrograms ml-1 of MX2 and ADM for 120 min and further incubated without drugs for 120 min after washing twice with medium. During incubation, real-time subcellular distribution of MX2 and ADM in living tumour cells were observed at various intervals using CLSM. For analysis of the in vivo uptake. Wistar rats bearing the C6 glioma were intravenously administered MX2 at a dose of 5 mg per kg body weight 60 min before sacrifice. The fluorescence of MX2 was predominantly seen in the cytoplasm in both C6 cells and T98G cells, although it was also present in the nucleus. In contrast, that of ADM was mainly confined to the nucleus in both cell lines. The fluorescent intensity of ADM in the nucleus after 120 min of exposure was approximately 1.5-fold higher than that of MX2 at the same dose exposure, probably indicating a greater amount of ADM accumulated in the nucleus than MX2. The influx and efflux of MX2 were much more rapid and greater than those of ADM in both cell lines. There was almost no difference in subcellular distribution among the doses tested in this study. The subcellular distribution of MX2 in vivo was almost similar to that of MX2 in vitro. These results suggest other mechanisms by which MX2 exerts its cytotoxic effects on tumour cells together with the inhibition of DNA topoisomerase II, which has been reported previously. It is considered that the CLSM technique is useful for the study of the cellular pharmacokinetics of antitumour agents such as anthracycline derivatives.

Animals↗

Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors.

The role of matrix metalloproteinases (MMP's) and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), in human brain tumor invasion was investigated. Gelatinolytic activity was assayed via gelatin zymography, and four MMP's (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 were immunolocalized in human brain tumors and in normal brain tissues using monoclonal antibodies. The tissue was surgically removed from 44 patients: glioblastoma (five cases), anaplastic astrocytoma (six cases), astrocytoma (four cases), metastatic tumor (six cases), neurinoma (10 cases), meningioma (10 cases), and normal brain tissue (three cases). Glioblastomas, anaplastic astrocytomas, and metastatic tumors showed high gelatinolytic activity and positive immunostaining for MMP's; TIMP-1 was also expressed in these tumors, but some tumor cells were negative for the antibody. Astrocytomas had low gelatinolytic activity and the tumor cells showed no immunoreactivity for MMP's and TIMP-1. Although neurinomas and meningiomas had only moderate proteinase activity and exhibited positive immunoreactivity for MMP-9, intense expression of TIMP-1 was simultaneously observed in these tumor cells. These findings suggest that MMP's play an important role in human brain tumor invasion, probably due to an imbalance between the production of MMP's and TIMP-1 by the tumor cells.

Adenocarcinoma↗

Immunohistochemical and ultrastructural study of skull base chordomas.

Eight chordomas were studied by using specific antibodies against cytokeratin, vimentin, desmin, type II collagen, S-100 protein, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). One chondrosarcoma was included as a representative of chondroid tumors. All chordomas were positively stained for epithelial markers (cytokeratin and EMA), whereas the chondrosarcoma was not. All chordomas and the chondrosarcoma expressed vimentin, type II collagen and S-100 protein. Oncofetal antigens (CEA and AFP) and desmin were found in five (63%) chordomas, whereas these antigens were not found in the chondrosarcoma. Ultrastructurally the chordoma cells showed junctional complexes, microvillous projections and basal lamina-like structures alongside the tumor cells, whereas the tumor cells of the chondrosarcoma had neither junctions and microvillous projections, nor basement membrane. The present study demonstrates the utility of these tumor markers and ultrastructural features in the differential diagnosis of chordomas and tumors with similar histologic patterns such as chondrosarcomas.

Adult↗

Prediagnostic serum selenium and zinc levels and subsequent risk of lung and stomach cancer in Japan.

Serum samples were collected in Hiroshima and Nagasaki, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973-1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (< 5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population.

Adult↗

Helicobacter pylori, dietary factors, and atrophic gastritis in five Japanese populations with different gastric cancer mortality.

In a cross-sectional study of 634 men aged 40 to 49 years, randomly selected from five areas of Japan with different rates of gastric cancer mortality, 121 men of 624 evaluated were diagnosed as having atrophic gastritis through serum pepsinogen I < 70 ng/ml and the pepsinogen I (PGI)/pepsinogen II (PGII) ratio < 3.0. We examined the relation of Helicobacter pylori (H. pylori) antibodies and dietary factors, including plasma level of antioxidant micronutrients, to the presence of atrophic gastritis. Presence of H. pylori IgG antibodies was associated with increased risk of atrophic gastritis (odds ratio [OR] = 1.9, 95 percent confidence interval [CI] = 1.1-3.3). As the level of plasma beta-carotene increased, we found a steady decrease in the risk of atrophic gastritis (OR for second quartile = 0.7, third quartile = 0.6, fourth quartile = 0.4, with CI = 0.2-0.8). Frequent intake of yellow vegetables also was associated with lower risk, while frequent intake of soybean products was related to increased risk. Although H. pylori antibodies, beta-carotene level, and intake of soybean products were all significant in the multivariate analysis, these factors did not explain the differences in atrophic gastritis prevalence among the five regions. The analysis of these risk factors in relation to each pepsinogen marker showed that although both H. pylori infection and low plasma beta-carotene were associated with the decreased level of serum PGI/II ratio, the former was derived from the increase of PGII, which is common in early stage of atrophic gastritis, and the latter from the decrease of PGI, which is specific to severe atrophic gastritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Modified procedure of monolayer culture of human pituitary adenoma cells on microporous membrane coated with extracellular matrix.

This study was designed to establish an in vitro model system in human hormone-producing pituitary adenoma which is analogous to the in vivo cellular environment. Mechanically dispersed cells composed of single cells and aggregated cells from 9 pituitary adenomas (5 GH-producing adenomas and 4 prolactinomas) were cultured on microporous membrane coated with basement membrane extract. Not only single cells but also large aggregated cells which usually float in the medium when seeded on ordinary plastic flasks were morphologically flattened and firmly attached to coated microporous membrane within a few days under the control of seeding medium volume. In both types of adenoma, surviving aggregated adenoma cells revealed well-preserved hormonal activity with regard to both cell morphology and hormone release after 6 m in culture and no undifferentiation of cell characteristics was observed. It is concluded that this culture method may further aid the investigation of in vitro cellular structure and function in human pituitary adenoma under conditions which closely mimic the in vivo cellular environment.

Adenoma↗

Does high gastric cancer risk associated with low serum ferritin level reflect achlorhydria? An examination via cross-sectional study.

With respect to the inverse association of serum ferritin level (SFL) with the risk of gastric cancer (GC) observed in some recent epidemiologic studies, possible mediation by achlorhydria as well as atrophic gastritis (AG), both of which are strongly associated with GC risk at not only the individual but also the population level, was examined in a cross-sectional study of 634 men aged 40 to 49 years randomly selected from 5 populations in Okinawa, Iwate, Nagano, Akita and Tokyo. AG and achlorhydria were serologically diagnosed based on the criteria of pepsinogen (Pep) I level < 70 ng/ml and Pep I/Pep II ratio < 3.0, as described previously, and a serum gastrin level of over 140 pg/ml, respectively. In the results, while the mean SFL for all the subjects differed significantly by area, similar areal differences in SFL were also found even when only the non-AG cases were considered. However, both of the above differences were eliminated with the exception of those between Okinawa and each of the other 4 areas, when adjustments were made for medical histories of diabetes mellitus, ulcers and liver disease, body mass index and gamma-glutamyltranspeptidase level. Therefore, no correlation among the 5 areas was observed between the adjusted areal mean SFLs and GC mortality in either case.(ABSTRACT TRUNCATED AT 250 WORDS)

Achlorhydria↗

[Individual differences in sympathetic nervous system responses to white noise stimuli: an investigation by finger plethysmogram].

Possible individual variations in the sympathetic nervous system response to sound stimuli were investigated using the auditory evoked plethysmogram response (AEPGR). This study consists of the following 3 experiments; (EXP1) the sound level-response relationships between white noise at 50, 70, and 90 dB (A) and AEPGRmax as defined below, (EXP2) individual variations of AEPGRmax to white noise at 90 dB (A), and (EXP3) the relationship between the AEPGR pattern and the urinary catecholamine (CA) excretion rate during sleep on the preceding night. The subjects were 35 young persons in (EXP1), and 79 young (18-28 yrs. old) and 35 old (60-83 yrs. old) persons in (EXP2) and (EXP3), respectively. The results were: (1) a good sound level-response relationship between the sound levels of 50, 70, and 90 dB (A) and AEPGRmax was obtained on average; (2) an AEPGRmax of more than 100% in response to the 90 dB (A) white noise was found in about 10% of the subjects, whereas it was below 100% in 90% of them. The time prior to the maximum response in the former case varied from 4.6 to 22.2 sec, which was quite a contrast to that of 3.0-9.0 sec in the latter case; (3) The NE (norepinephrine), E (epinephrine) and DA (dopamine) excretion rates were shown to be significantly higher in the former group in (2) than in the other groups, regardless of adjustment for age, blood pressure and/or ECG findings. Thus, it is suggested that the cardiac response to E secreted from the adrenals due to white noise stimuli was predominant in the former group in (2). Therefore, this response pattern was called the AEPGR "beta type", whereas the other group was designated the "alpha type", since its AEPGR appeared to reflect only vasoconstriction. The suggested individual differences in AEPGR associated with increased night-rest catecholamine secretion were also discussed in relation to their possible relevance to chronic stress, neuroticism and other conditions.

Adolescent↗

EEG power spectrum changes due to listening to pleasant music and their relation to relaxation effects.

Electroencephalogram (EEG) power spectrum changes induced by pleasant music (2-min. fractions of 6 samples of music [famous classical and commercially available "alpha music" at 10-sec. intervals]) were investigated in relation to changes in 16 kinds of psychosomatic feelings. Subjects were 42 healthy young people aged 18-25 yrs. Two major components, "pleasant & relaxed" and "calm", were extracted through principal component analysis of the feeling changes, both of which were related to the "relaxation effects" of the music. These component scores were not related to the changes of EEG powers in the delta, theta, alpha and beta frequency components in 6 regions (frontal, parietal and occipital regions of the left and right hemispheres), when examined separately. However, the change of the total delta power for all the regions was significantly associated with both the "pleasant & relaxed" and "calm" component scores. The association between the total theta power change and "calm" score was found to be insignificant if the type-A personality variable was added to their regression model. On the other hand, the alpha-peak frequency was inversely related to the decrease of the "calm" score in the left occipital region (LO). The reduction of the alpha-peak power in the LO was also significant, and was associated not with the alpha-peak frequency changes but inversely with the "calm" score, although these alpha-component changes were not shown to be modified by the personality. Thus, the present study suggests, as a preliminary finding, that the "relaxation effects" of pleasant music can be associated with the EEG power spectrum component changes, especially with the change in the total theta power and possibly with that in the alpha power in the occipital, and the frequency shift of the peak in the alpha-range. Some of the associations were also shown to vary for the type-A personality, suggesting a clue to relating the personality to a differential stress-related psychosomatic trait, although the physiological significance of the changes in the low-frequency component range as well as those in the alpha-frequency component, which are obtained through FFT, should be further clarified.

Adolescent↗

Light and electron microscopic observation of the same mammosomatotroph cell in a mixed growth hormone- and prolactin-secreting pituitary adenoma--case report.

A mammosomatotroph cell was identified in two consecutive semithin sections of conventional epoxy-embedded tissue for light microscopy and an adjacent ultrathin section for electron microscopy cut from a mixed growth hormone (GH)- and prolactin (PRL)- secreting human pituitary adenoma in a 51-year-old female. The same mammosomatotroph cell demonstrated immunostaining for both GH and PRL simultaneously by light microscopy, and was morphologically evaluated by electron microscopy. The ultrastructural features of this cell resembled densely granulated GH-secreting adenoma cells, but also contained characteristics of PRL-secreting adenoma cells.

Adenoma↗

Diurnal variation of plasma minerals and trace elements in a group of Japanese male adults.

When the nutritional status of minerals and essential trace elements is assessed by their levels in plasma, intra-individual variation in the measured values, particularly diurnal variation, must be considered. In this paper, concentrations of nine elements (Na, Mg, P, K, Ca, Fe, Cu, Zn, and Se) in plasma collected 7 times in a 24-h period from 10 healthy Japanese adults were measured with hemoglobin and plasma concentrations of proteins (total protein, albumin, retinol binding protein (RBP), ceruloplasmin, and transferrin), total cholesterol, and cortisol. Then the pattern of diurnal variation in, and the interrelationships among, these parameters were clarified in subjects who consumed an ordinary meal. Significant diurnal variation examined by two-way analysis of variance (variations due to subject and sampling time) was found for Zn, RBP, and cortisol. Plasma Zn level was higher in the forenoon samples than in those taken in the afternoon. The pattern of diurnal variation found for cortisol was similar to, but slightly different from, that for Zn. The correlation coefficient between Zn and cortisol was significant (r = 0.555) using the standardized values for individuals, and in the result of multiple regression analysis, cortisol level was selected as the significant explanatory factor for Zn variation; however, the sampling time was the most significant factor. For other elements besides Zn, no significant diurnal variation was found. Moreover, no meaningful factors were selected for variations of those elements in the result of multiple regression analysis. These results indicate that, in assessing Zn nutriture with its plasma levels, it is necessary to unify the sampling time.

Adult↗