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Biomedical subjects

N Shikata

Publications and source records attributed to N Shikata.

At least 19 recordsLinked to original sources

Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition.

The concentrations of free amino acids in plasma change coordinately and their profiles show distinctive features in various physiological conditions; however, their behavior can not always be explained by the conventional flow-based metabolic pathway network. In this study, we have revealed the interrelatedness of the plasma amino acids and inferred their network structure with threshold-test analysis and multilevel-digraph analysis methods using the plasma samples of rats which are fed diet deficient in single essential amino acid. In the inferred network, we could draw some interesting interrelations between plasma amino acids as follows: 1) Lysine is located at the top control level and has effects on almost all of the other plasma amino acids. 2) Threonine plays a role in a hub in the network, which has direct links to the most number of other amino acids. 3) Threonine and methionine are interrelated to each other and form a loop structure.

Amino Acids, Essential↗

Association between nasal respiratory obstruction and vertical mandibular position.

Vertical mandibular position is considered to have an effect on the patency of the upper airway, because mouth opening is associated with a backward and downward displacement of the mandible and tongue. This study was conducted to investigate the nature of mandibular displacement at rest and to determine whether or not different respiration modes and body postures influence the mandibular position. The mandibular position was measured by use of a newly developed system with magnets and magnetic sensors placed on the upper and lower first molars, respectively. Vertical mandibular position was significantly affected by the degree of nasal airway obstruction. The proportion of the duration of mouth opening from 0 to 2.5 mm was about 80% in the sitting and lateral recumbent positions and 55% in the supine position. The amount and duration of vertical mandibular displacement were thus significantly increased by experimentally induced nasal respiratory obstruction. Furthermore, it was demonstrated that the amount and duration of mouth opening were significantly greater in the supine posture than in the sitting and lateral recumbent positions. It is thus shown that nasal respiratory disturbance may be a key determinant for mouth opening and breathing and the resultant vertical mandibular displacement.

Adult↗

Trichilemmoma: an immunohistochemical study of cytokeratins.

BACKGROUND: The histogenesis of trichilemmoma remains unclear. OBJECTIVES: To clarify the histogenesis of trichilemmoma by evaluating its cytokeratin (CK) expression. METHODS: In three cases of trichilemmoma, CK expression was studied immunohistochemically using seven antikeratin antibodies against CK1, 10, 14-17 and 19, respectively. RESULTS: CK1 and CK10 were present in keratinizing ductal epithelium. CK14 was present in the whole layer. CK15 was present in suprabasal layers in two cases. CK16 was present in the suprabasal layer, but was absent in keratinizing ductal epithelium. CK17 was present in suprabasal layers and the sebaceous duct-like structure. CK19 was totally absent. CONCLUSIONS: These results showed that trichilemmoma may differentiate mainly towards two directions: infundibular keratinization and proliferation of the outer root sheath with undifferentiated and pluripotent characteristics.

Adult↗

An electromyographic evaluation of the bilateral symmetry and nature of masticatory muscle activity in jaw deformity patients during normal daily activities.

This study was designed to investigate the nature of masticatory muscle activity and the balance in the bilateral symmetry of the masticatory muscle activity in jaw deformity patients. Fifteen patients (19.9 +/- 5.3 years) with lateral shift of the mandible caused by transverse craniofacial deformity and 15 controls (28.6 +/- 1.9 years) were used as the subjects in this study. Surface electromyographic (EMG) activities were recorded from the bilateral masseter and anterior temporal muscles during daytime (142 min, including mealtime) and sleep (142 min). The averaged rectified EMG values were normalized with reference to the EMG amplitude induced by a 98-N bite force. Bilateral symmetry of masseter and anterior temporal muscle activities was examined using an asymmetry index (AI) for both the controls and the patients. The normalized activities of the masseter and anterior temporal muscles during normal daily activities were lower in patients than in the controls. Asymmetry indices in patients were significantly greater during usual daytime activities and sleep for the anterior temporal muscle and significantly smaller during sleep for the masseter muscle as compared with the controls. The results show that masticatory muscle activity is lower in these jaw deformity patients in association with more prominent asymmetry of anterior temporal muscle activity than in the controls. It is suggested that these findings are highly relevant to occlusal interference and instability because of malocclusion and lateral mandibular deviation.

Adult↗

Effects of activator on masticatory muscle activity during daytime and sleep.

The purpose of this study was to investigate masticatory muscle activity with and without the use of an activator during daytime and sleep, and further to focus on the changes in muscle activity produced by the daytime use. The subjects in this study were 10 healthy males (mean age: 27.6 years). A portable electromyogram (EMG) recording device was used to record the activity from the right temporal, masseter and digastric muscles. After recording, the integrated EMG values (microV s) were measured. The muscle activity was lower during sleep than during daytime, irrespective of the use of the activator. In sleep-time, temporal and digastric muscle activity was significantly decreased, although masseter muscle activity presented no significant differences. With the activator in use, the digastric muscle activity tended to increase in comparison with the elevator muscles during daytime and sleep. Although the activity of both elevator muscles was diminished by use of the activator during sleep in all subjects, some subjects showed an increase during daytime. These results suggested that the activator should be used, if possible, not only during sleep, but also during daytime and clenched on consciously to obtain the adaptation and development of the masticatory muscles for the 're-training of the muscles' at a new favourable mandibular position.

Adult↗

Cytokeratin expression in pilonidal sinus.

BACKGROUND: Pilonidal sinus (PS) is considered to belong in the category of follicular occlusion diseases (acne triad). OBJECTIVES: The aim of our study was to elucidate the pathogenesis of PS by evaluating its cytokeratin (CK) expression. METHODS: CK expression in nine cases of PS was studied immunohistochemically using six antikeratin antibodies. RESULTS: Infundibular-like epithelium contained CK1, 10 and 14 similar to normal infundibulum, but it did not contain CK17. In non-infundibular-like epithelium, CK14, 16 and 17 were detected similar to that in normal outer root sheath. CK expression in PS was similar to that in hidradenitis suppurativa, suggesting that sinus epithelium may be fragile, hyperproliferative and undifferentiated. CONCLUSIONS: PS can be classified in the same entity as follicular occlusion diseases based on CK expression.

Adult↗

Mechanisms of adrenal damage induced by 7,12-dimethylbenz (alpha) anthrancene in female Sprague--Dawley rats.

The mechanisms of adrenal damage induced by 7,12-dimethylbenz (alpha) anthrancene (DMBA) in 50-day-old female Sprague--Dawley rats were investigated. A single dose of DMBA, either fed (30 mg) per os or injected (6 mg) in a caudal vein, caused inner cortical cell death (cells of the zonae fasciculata and reticularis) by an apoptotic mechanism. Apoptotic cells were identified by cell morphology, and terminal dUTP nick end labeling (TUNEL)-positive cells were seen at 12 hrs post-DMBA, reached a maximum at 36 h, and were accompanied by blood congestion followed by massive hemorrhage leading to post-apoptotic necrosis at 48 and 72 h. The apoptotic cascade involved the up-regulation of Bax, the down-regulation of Bcl-2, and the activation of caspase-3. At 72 h, regeneration as evidenced by the appearance of 5-bromo-2'-deoxyuridine-positive cells began to occur in the damaged inner cortical zones, with the cells proliferating toward the medulla thereafter. Regenerative cells expressed cytochrome P450 11 beta hydroxylase. The damage was repaired but calcification appeared at 2 weeks post-DMBA, leaving bow-shaped lesions in some adrenals.

9,10-Dimethyl-1,2-benzanthracene↗

Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator.

Resveratrol is a naturally occurring product found in grapes and wine. The effect of synthetic resveratrol on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MKL-F) human breast cancer cell lines was examined. Resveratrol at low concentrations caused cell proliferation in ER-positive lines (KPL-1, < or = 22 microM; MCF-7, < or = 4 microM) whereas at high concentrations (> or = 44 microM) it caused suppression of cell growth in all three cell lines examined. Growth suppression was due to apoptosis as seen by the appearance of a sub-G1 fraction. The apoptosis cascade up-regulated Bax and Bak protein, down-regulated Bcl-xL protein, and activated caspase-3. Resveratrol (52-74 microM) antagonized the effect of linoleic acid, a potent breast cancer cell stimulator, and suppressed the growth of both ER-positive and -negative cell lines. Thus, resveratrol could be a promising anticancer agent for both hormone-dependent and hormone-independent breast cancers, and may mitigate the growth stimulatory effect of linoleic acid in the Western-style diet.

Anticarcinogenic Agents↗

A quantitative electromyographic analysis of masticatory muscle activity in usual daily life.

OBJECTIVE: This study was designed to investigate whether a quantitative electromyographic (EMG) analysis with a special reference to the EMG amplitude at 98N bite force could reduce the influence of electrode relocation and to examine the reproducibility of masticatory muscle activity in usual daily life within individuals. SUBJECTS AND METHODS: In the first experiment, two sessions of surface EMG recording for masseter and anterior temporal muscles during tapping, and chewing gum and marshmallow were performed for 10 subjects with an interval of at least 1 week with electrode relocation. In the second experiment, two sessions of EMG recording during daytime (142 min, including mealtime) and sleep (142 min) were carried out for 10 subjects with an interval of at least 1 week. The average rectified EMG values were normalised with a special reference to the EMG amplitude induced by a 98N bite force. RESULTS: In the first experiment, high correlation coefficients and no significant differences in the mean normalised values of muscle activity were found between two sessions. Although the average rectified values showed high correlation coefficients, the mean masseter muscle activity while chewing gum was significantly different between two sessions. In addition, the variation in temporal muscle activity between two sessions while chewing gum was significantly smaller in the normalised values than in the average rectified ones. In the second experiment, less intra-individual variation in the normalised values of masticatory muscle activity between two sessions indicated the reproducibility. Normalised masticatory muscle activity showed less variation during mealtimes than during usual daytime and sleep. CONCLUSIONS: This quantitative EMG analysis could estimate the masticatory muscle activity by reducing the influences of electrode relocation, demonstrating an availability of this analysis for the evaluation of masticatory muscle activity in usual daily life.

Activities of Daily Living↗

Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in stage IIIB cervical carcinoma.

BACKGROUND: The relative amounts of Bcl-2 and Bax proteins determine cell survival or death following an apoptotic stimulus. To clarify the molecular mechanism of cell death after radiotherapy or thermoradiotherapy and its relation to the response of AJCC/UICC Stage IIIB cervical carcinomas, the expression of Bax and Bcl-2 proteins was investigated both before and in the course of treatment given during this study. METHODS: Thirty-seven patients with Stage IIIB carcinoma of the uterine cervix were treated with external beam irradiation to the pelvis combined with iridium-192 high-dose-rate intracavitary brachytherapy. All patients were randomized to one of the following two groups: the radiotherapy (RT) group of 19 patients who were given radiotherapy alone, and the thermoradiotherapy (TRT) group of 18 patients who were given 3 sessions of hyperthermia in addition to RT. Specimens of the cervical tumors were obtained by punch biopsy both before and in the course of the treatment (after a total dose of 10.8 grays ¿Gy for the RT group or after 10.8 Gy plus 1 session of hyperthermia for the TRT group). The tumor sections were stained with anti-Bax and anti-Bcl-2 monoclonal antibody. On the basis of the percentage of immunopositive cells, both pretreatment and posttreatment samples were scored. Furthermore, relative changes in protein expression were determined by comparing the pretreatment scores with those in the course of treatment. In addition, treatment response was evaluated. RESULTS: A complete response was achieved in 52.6% (10 of 19) of the RT group versus 83. 3% (15 of 18) of the TRT group (P = 0.049). Better tumor control was accompanied by increased Bax expression, i.e., 10.5% (2 of 19) of the RT group versus 44.4% (8 of 18) of the TRT group (P = 0.02). The respective number of patients who partially responded (PR) or did not respond to treatment (NC) was 26.3% (5 of 19) and 21.1% (4 of 19) of the RT group versus 11.1% (2 of 18) and 5.6% (1 of 18) of the TRT group (P = 0.2 for both the PR and NC subgroups). CONCLUSIONS: TRT was found to result in better treatment responses than RT for patients with Stage IIIB cervical carcinoma. An additive or synergistic antitumor effect of TRT is likely to occur through induction of apoptosis involving one of the bax pathways.

Aged↗

Caspase-3 inhibitor rescues N -methyl- N -nitrosourea-induced retinal degeneration in Sprague-Dawley rats.

The effect of a caspase-3 inhibitor on N -methyl- N -nitrosourea (MNU)-induced retinal degeneration was investigated. Sixty mg kg(-1)MNU was given intraperitoneally to 50 day old female Sprague-Dawley rats, and 4000 ng Ac-DEVD-CHO, a caspase-3 inhibitor, was injected intravitreally twice at 0 and 10 hr after MNU. In both peripheral and central retina, an apoptotic index of the photoreceptor cells 24 hr after MNU treatment was calculated by TUNEL labeling, and retinal damage 7 days after MNU treatment was evaluated from retinal thickness and a retinal damage ratio (length of damaged retina : whole retinal length). In MNU-treated rats, the TUNEL index 24 hr post-MNU was 79.5% in the peripheral and 83.7% in the central retina, while the Ac-DEVD-CHO injection significantly reduced it to 59.7 and 71.8%, respectively. Total retinal thickness 7 days after MNU was 38 microm in the peripheral and 75 microm in the central retina. Ac-DEVD-CHO injection increased these values to 72 and 77 microm, respectively. The retinal damage ratio 7 days after MNU was 98.5%. Ac-DEVD-CHO injection significantly reduced this value to 54.4%. The use of a caspase-3 inhibitor was effective in the suppression of MNU-induced retinal apoptosis and may be a therapeutic intervention in human retinitis pigmentosa.

Animals↗

Time-specific occurrence of alopecia in neonatal C57BL mice treated with N-methyl-N-nitrosourea and the therapeutic efficacy of tacrolimus hydrate.

Alopecia was induced in male and female neonatal C57BL mice by a single intraperitoneal injection of 60 mg/kg N-methyl-N-nitrosourea (MNU). MNU administration was most effective in the 8-day-old mice and less effective in the 5-day-old mice (at active and early anagen stages of the first hair cycle, respectively). No alopecia was seen in the day 14 MNU-treated animals (at telogen stage of the first hair cycle). MNU effectively induced hair follicular cell apoptosis at the anagen stage by up-regulation of Bax protein without down-modulation of Bcl-2 protein. In day 8 MNU-treated mice, the immunosuppressive agent 0.01% tacrolimus hydrate (FK506), when topically applied for 5 days from 1 day after MNU treatment (before the occurrence of alopecia), decreased the severity of alopecia. However, it did not stimulate hair growth when applied for 5 days from 20 days of age (after occurrence of alopecia).

Alkylating Agents↗

Mucinous carcinoma of the breast with neuroendocrine differentiation.

A case of mucinous carcinoma of the breast with neuroendocrine differentiation in an 89-year-old woman is presented. The patient presented with a rapidly growing right breast mass, which she had had for 2-3 years. The tumor, 15 x 8 x 5 cm, was located mainly in the upper outer quadrant. Light microscopy revealed a pure mucinous carcinoma of type B. Neuroendocrine differentiation was demonstrated by Grimelius stain and chromogranin A, as well as the presence of neurosecretory granules. The breast cancer cells were of luminal origin and had dedifferentiated to attain neuroendocrine properties.

Adenocarcinoma, Mucinous↗

Long-term ethanol consumption in ICR mice causes mammary tumor in females and liver fibrosis in males.

BACKGROUND: Although epidemiological studies indicate that ethanol consumption and the risk of breast cancer are positively associated in women, experimental animal models have not yet been developed that provide evidence to support this relationship. To clarify alcohol-related liver injury, it is important to reproduce, in laboratory small animals, the liver fibrosis observed in human alcoholics. However, in mice the induction of fibrosis has failed. The present study describes the first experimental models to produce mammary tumors in female ICR mice and liver fibrosis in male ICR mice treated long-term with ethanol. METHODS: The study consisted of two parts. To induce mammary tumors, female ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 25 months, with solid diet supplied ad libitum. To induce liver fibrosis, male ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 10 to 15 months. Control female and male mice were given tap water. RESULTS: In 9 (45%) of 20 ethanol-treated female mice, mammary tumors occurred at 8 to 24 months after ethanol intake began, whereas spontaneous mammary tumor was not found in the 20 control female mice. The tumors were composed histopathologically of either papillary adenocarcinoma or medullary adenocarcinoma of glandular epithelial origin. In the ethanol-treated male mice, early hepatic fibrosis at the centrilobular and pericellular areas and central-central bridging were observed at the 10th month, and marked fibrosis at the centrilobular, pericellular, and periportal areas and bridging between the neighboring vascular tissues were observed at the 15th month, which suggested that the initial fibrosis arose from the centrilobular area. No abnormalities other than mild fatty infiltration were found in livers of the control male mice. CONCLUSIONS: These murine models may be useful to study the role of ethanol in mammary tumorigenesis and the pathogenetic mechanisms of ethanol liver injury.

Animals↗

Retinal damage induced by cisplatin in neonatal rats and mice.

PURPOSE: The morphologic response of the retina at different neonatal ages to various doses of cis-platinum(II)diamminedichloride (cisplatin) was examined in rats and mice. METHODS: Cisplatin was given to rats at a dose of 1, 3 or 5 mg/kg at 0 days or 5 mg/kg at 7 or 14 days of age, and to mice at 0.5, 1.5, 3 or 6 mg/kg at 0 days or 6 mg/kg at 7 or 14 days of age, and the animals examined 12 and 24 hrs, and 3 and 7 days after the treatment. RESULTS: In both species, regardless of gender, with > or = 3 mg/kg cisplatin treatment (lethal dose) at day 0, retinal damage characterized by the appearance of aggregations of TUNEL-positive cells scattered in the undifferentiated neuroblastic layer was seen at 24 hrs, and led to rosette formation at day 3 and 7 (retinal dysplasia). At the ultrastructural level, neuroblastic cells showed condensation of chromatin and shrinkage of the cytoplasm, and rosettes encircled by an outer limiting membrane. Cell debris phagocytosed by pigment epithelial cells was seen. However, cisplatin at < 3 mg/kg in 0-day-old animals or at high dose in > or = 7-day-old animals caused no damage to the retina. CONCLUSIONS: A critical period (day 0) for the administration and a threshold dose (> or =3 mg/kg) of cisplatin in the development of retinal damage in rats and mice was seen. Although the cisplatin dose necessary to damage the retina caused a high incidence of mortality, it was below the human therapeutic dose.

Aging↗