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Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 37 records · Page 2Linked to original sources
PubMed2002

Location, arrangement and possible function of interodontoblastic collagen fibres in association with calcium hydroxide-induced hard tissue bridges.

AIM: To assess the location, arrangement and possible function of interodontoblastic collagen fibres in association with calcium hydroxide-induced hard tissue bridges by using light and transmission electron microscopy techniques and immunohistochemical staining localization. METHODOLOGY: Prior to the study, an animal use protocol form was reviewed and approved by the Screening Committee for Animal Research of the Tokyo Medical and Dental University. Exposed monkey pulps were capped with a hard-set calcium hydroxide and histopathologically evaluated at 3, 14, 21, 30 and 90 days, using light microscopy with silver staining and transmission electron microscopy to differentiate structural features of interodontoblastic collagen fibres. In addition, an attempt was made to identify and to differentiate between several types of collagen and fibronectin using immunohistochemical localization techniques. RESULTS: At 14 days, interodontoblastic collagen fibres were observed extending from the original dentine, passing through the odontoblasts, and consisted of two portions: a thick fibril and a thin fibril. At 21 days, interodontoblastic collagen fibres were seen penetrating into the predentine and becoming incorporated into the mineralized dentine. At 30 days, interodontoblastic collagen fibres reached the cell process. Although interodontoblastic collagen fibres were no longer observed near the odontoblastoid cells at the area of the newly formed tubular dentine, interodontoblastic collagen fibres were observed embedded within the primary formed dentine bridge. Immunohistochemical staining demonstrated type I collagen and fibronectin within the interodontoblastic collagen fibres. CONCLUSIONS: Interodontoblastic collagen fibres were routinely detected throughout early dentine bridges. Interodontoblastic collagen fibres are thought to be important for initial dentine bridging to induce and support a dentinogenesis framework.

Animals↗
PubMed2002

Development of a health guidance support system for lifestyle improvement. Committee of Health Evaluation Support System Council of Japan AMHTS Institutions.

OBJECTIVE: To provide automated advice for lifestyle adjustment based on an assessment of the results of a questionnaire and medical examination or health checkup data. METHODS: A system was developed that gathers data based on questions regarding weight gain, exercise, smoking, sleep, eating habits, salt intake, animal fat intake, snacks, alcohol, and oral hygiene; body mass index, resting blood pressure, fasting blood sugar, total cholesterol, triglycerides, uric acid and liver function tests. Based on the relationships between the lifestyle data and the health checkup data, a health assessment sheet was generated for persons being allocated to a multiple-risk-factor syndrome group. RESULTS: Health assessment and useful advice for lifestyle improvement were automatically extracted with the system, toward the high risk group for lifestyle related diseases. The system is operational. CONCLUSIONS: We developed a health guidance support system for lifestyle improvement. In comparison with conventional, limited advice methods, we developed a practical system that defined the necessity for lifestyle improvement more clearly, and made giving advice easier.

Counseling↗
PubMed2002

Theoretical considerations on the health checkup accuracy of combination testing.

OBJECTIVES: To find basic theoretical evidence for an optimum combination of multi-phasic health checkup testing obtained by considering how the health checkup accuracy changes with the number of tests (n) and kinds of combination methods (A, B, C, D and E). METHODS: To find how the health checkup accuracy changes with the number of tests and type of combination method, generalized formulas as functions of the number of tests, are obtained to calculate the over-all health checkup accuracy which is defined by sensitivity (alpha), specificity (beta) and odds-ratio (gamma), based on the two-by-two table. Five kinds of combination methods were considered: A) Sequential tests. B) Sequential tests after changing the order in A. C) Simultaneous tests using the Believe-the-Negative Rule. D) Simultaneous tests using the Believe-the-Positive Rule. E) Simultaneous tests using the Believe-all-Positive-all-Negative Rule. RESULTS: It was proved that combination methods A, B and C are "equivalent" for health checkup accuracy. Therefore, the five methods could be summarized into three patterns. For A, B and C: beta and gamma increased but a decreased with increasing n. For D: alpha increased but beta and gamma decreased with n. For E: alpha, beta and gamma increased with n. CONCLUSION: Health checkup accuracy of combination testing is the best in case of E, although problems exist concerning how to judge the borderline subjects.

Humans↗
PubMed2001

Circadian profile of Per gene mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, and pineal body of aged rats.

Aging alters circadian components such as the free-running period, the day-to-night activity ratio and photic entrainment in behavioral rhythms, and 2-deoxyglucose uptakes and neuronal firing in the suprachiasmatic nucleus (SCN). A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which Period (Per) and Cryptochrome (Cry) genes play a role in negative feedback. The circadian rhythm systems include photic entrainment, clock oscillation, and outputs of clock information such as melatonin production. In this experiment, we examined clock gene expression to determine whether circadian input, oscillation, and output are disrupted with aging. Circadian expression profiles of rPer1, rPer2, or rCry1 mRNA were very similar in the SCN, the paraventricular nucleus of the hypothalamus (PVN), and the pineal body of young and aged (22-26 months) rats. On the other hand, the photic stimulation-induced rapid expression of Per1 and Per2 in the SCN was reduced with aging. The present results suggest that the molecular mechanism of clock oscillation in the SCN, PVN, and pineal body is preserved against aging, whereas the impairment of Per1 induction in the SCN after light stimulation may result in impaired behavioral photic entrainment in aged rats.

Aging↗
PubMed2001

Visualization of mPer1 transcription in vitro: NMDA induces a rapid phase shift of mPer1 gene in cultured SCN.

Many physiological and behavioral phenomena are controlled by an internal, self-sustaining oscillator with a periodicity of approximately 24 hr. In mammals, the principal oscillator resides in the suprachiasmatic nucleus (SCN). A light pulse during the subjective night causes a phase shift of the circadian rhythm via direct glutamatergic retinal afferents to the SCN [1]. Along with the accepted theoretical models of the clock, it is suggested that behavioral resetting of mammals is completed within 2 hr [2]; however, the molecular mechanism has not been elucidated. Here, we show the real-time image of the transcription of the circadian-clock gene mPer1 in the cultured SCN by using the transgenic mice that carry a luciferase reporter gene under the control of the mPer1 promoter [3]. The real-time image demonstrates that the mPer1 promoter activity oscillates robustly in a circadian manner and that this promoter activity is reset rapidly (within 2-3 hr) when a phase shift occurs.

2-Amino-5-phosphonovalerate↗
PubMed2001

Cloning of a novel 2',5'-oligoadenylate synthetase-like molecule, Oasl5 in mice.

The 2',5'-oligoadenylate synthetase (2-5OAS) is a enzyme that catalyzes synthesis of 2',5'-oligoadenylates (2-5A) in a dsRNA-dependent manner, and known as a major component of the IFN-induced host defense mechanisms against microbial infections. Here, we report the presence of a novel 2-5OAS-like molecule, termed Oasl5, in mice. The size of Oasl5 cDNA was about 2 kb and encoded a protein consisting of 362 aa. The amino acid sequence showed 76% similarity to the mouse 2-5OAS, however, several motifs being important for the enzyme activity were not conserved. The Oasl5 mRNA was most significantly expressed in the brain, and relatively weak expression was found in other organs such as the spleen, kidney, ovary and testis. It was also expressed in embryonic stem (ES) cells. The Oasl5 mRNA expression in ES cells was elevated 5-fold after treatment with IFN and about 2-fold in the brain when stimulated with IFN inducer, polyinosinic-polycytidylic acid (poly[I:C]). In situ hybridization analysis revealed that Oasl5 is expressed in neurons in the central nervous system in adult mice. When Oasl5 was expressed in E. coli, it yielded 42 kDa protein that binds to dsRNA, but it did not show oligoadenylate synthetase activity. These findings suggest a novel function of Oasl5, which are independent of oligoadenylate synthetase activity, in the brain and developing embryos.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

Uncoupling protein 3 and peroxisome proliferator-activated receptor gamma2 contribute to obesity and diabetes in palauans.

We examined the genetic contribution of single nucleotide polymorphisms (SNPs) of the energy metabolism-related genes, including beta 3 adrenergic receptor (beta3AR), apolipoprotein E (apo-E), promoter of uncoupling protein 3 (UCP3-p), peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) and leptin receptor (LEPR) to metabolic disorders, in 118 inhabitants of Palau. The data were statistically analyzed and ethnically compared to correlate SNPs and their metabolic parameters. UCP3-p (P < 0.01) and PPARgamma2 (p = 0.05) correlated with plasma HbA1c, and UCP3-p correlated with fasting blood glucose (P < 0.01) in males, but not in females. UCP3-p correlated with body fat (%) (P < 0.01) in females, but not in males. Plasma leptin levels and apo-E were correlated in both groups. The frequency of SNPs for PPARgamma2, LEPR, and UCP3-p are significantly different between Palauans and Caucasians.

Adipose Tissue↗
PubMed2001

Expression of the Per1 gene in the hamster: brain atlas and circadian characteristics in the suprachiasmatic nucleus.

Recent progress in study on the molecular component of mammalian clocks has claimed that mammals and Drosophila share the similar fundamental clock oscillating system. In the present study, we investigated expression of Per1, the first gene of the mammalian homolog of the Drosophila clock gene period, in the hamster brain, and we also examined its circadian expression pattern in the mammalian clock center, the suprachiasmatic nucleus (SCN). In situ hybridization using isotope-labeled cRNA probes revealed a wide and region-specific distribution of Per1 in the hamster brain and spinal cord. High levels of Per1 were found in the internal granular layer of the granular cells of the olfactory bulb, anterior olfactory nuclei, tenia tecta, olfactory tubercle, piriform cortex, suprachiasmatic nucleus, and gyrus dentatus of hippocampus. Moderate levels of expression were detected in many brain regions including the granular layer of the cerebellum, anterior paraventricular thalamic nucleus, caudate-putamen, inferior colliculus, pontine nuclei, inferior olive, and nucleus of the solitary tract. We examined the circadian profile of hamster Per1 mRNA in the SCN in constant darkness and found that Per1 expression showed a peak at subjective day (circadian time [CT] 4) and formed a trough at subjective night (CT16-CT20). A brief exposure of light at CT16 could acutely induce large quantities of Per1 mRNA in the hamster SCN, except for its dorsomedial subdivision. These findings suggest that the characteristics of Per1 gene expression in the mammalian circadian center (showing a peak in the daytime and a trough in the nighttime and a rapid inducibility by light) are common among mammalian species. Lastly, in hamster brain, Per1 gene is also inducible in extra-SCN brain nuclei, since light at night also elicited Per1 mRNA in neurons of the hypothalamic paraventricular nucleus.

Animals↗
PubMed2001

Additive effect of mPer1 and mPer2 antisense oligonucleotides on light-induced phase shift.

It is well known that light induces both mPer1 and mPer2 mRNA in the suprachiasmatic nucleus. We have reported that mPer1 antisense oligonucleotides (ODNs) inhibited the light-induced phase delays of mouse locomotor rhythm. In this study, we asked whether both or either mPer1 or mPer2 expression is necessary to induce the phase shift. We examined the effects of inhibition of mRNA expression on light-induced phase delays of mouse circadian behavior rhythm. Light-induced phase delays were moderately attenuated by microinjection of mPer1 or mPer2 antisense ODN, but not by mPer3 antisense or mPer1, mPer2 scrambled ODNs, whereas following simultaneous injection of both mPer1 and mPer2 antisense ODNs they disappeared. The present results suggest that acute induction of mPer1 and mPer2 gene play an additive effect on photic entrainment.

Animals↗
PubMed2001

Acute adrenal failure associated with fluconazole after administration of high-dose cyclophosphamide.

A 63-year-old man received high-dose cyclophosphamide for peripheral blood stem-cell (PBSC) harvest. He received 200 mg fluconazole. On day 3, atrial fibrillation developed with blood pressure declining to 78 mmHg. The rapid adrenocorticotropin (ACTH) test showed blunted adrenal responses. He was suspected as having adrenal failure, and fluconazole was discontinued. The rapid ACTH test became normal on Day 14, and PBSCs were successfully harvested. To clarify the association between adrenal failure and fluconazole, we resumed 400 mg fluconazole on Day 16 and repeated the test on Day 21, which showed blunted adrenal responses. This case demonstrates that prophylactic use of fluconazole can cause adrenal insufficiency.

Adrenal Insufficiency↗
PubMed2001

Diagnostic potential of short echo time MR spectroscopy of gliomas with single-voxel and point-resolved spatially localised proton spectroscopy of brain.

Accurate neuroimaging grading of gliomas is useful for management, but techniques such as MRI and CT are not sufficiently reliable. Necrosis is a consistent, decisive prognostic factor and the key diagnostic criterion for glioblastoma multiforme. MR spectroscopy (MRS) allows noninvasive measurement of metabolites in brain tumours and mobile lipids reflect necrosis. However, short echo-time (TE) spectroscopy has been required for reliable assessment of lipids, since their relaxation times are very short. Recent advances have made it possible to perform short-TE MRS. We attempted to evaluate the significance of short TE spectroscopy as part of routine imaging for diagnosis and grading of gliomas. We performed TE 30 ms MRS in 25 patients with gliomas (grade II six; grade III three; grade IV, 16) and in 19 areas of healthy white matter using proton brain examination/single voxel (PROBE/SV) and point-resolved spatially localised spectroscopy (PRESS). With short-TE spectroscopy, lipid signals were detected in all 16 tumours of grade IV, one grade II (P = 0.0002) and none of grade III (P = 0.001). TE 136 ms MRS, carried out in 20 of these cases, showed lipid signals in only four of 14 grade IV tumours and in none of the other six. N-acetylaspartate/choline (NAA/Cho) ratios were always more than 1.0 in healthy tissues and less than 1.0 in all but one of the gliomas. The mean creatine (Cr)/Cho ratio in each tumour grade was significantly lower than in the healthy tissues. The mean Cr/Cho ratio was also significantly lower in grade IV than in grade II tumours (P < .0005). Considerable overlap in Cr/Cho ratio was observed between grade II and grades III and IV gliomas at long but less so at short-TE MRS. We conclude that short-TE MRS with PROBE/SV and PRESS is of value in grading gliomas.

Adolescent↗
PubMed2001

Continuous infusion prochlorperazine: pharmacokinetics, antiemetic efficacy, and feasibility of high-dose therapy.

PURPOSE: The purpose of these sequential phase I studies was to evaluate the antiemetic efficacy and pharmacokinetics of high-dose continuous infusion prochlorperazine. METHODS: A total of 52 patients with advanced cancer were treated in two sequential phase I studies utilizing high-dose prochlorperazine. In study 1, designed to investigate the antiemetic effects of dose-intensive prochlorperazine, various cisplatin-based multiagent chemotherapeutic regimens were administered in combination with escalating doses of prochlorperazine. In study 2, a fixed dose of cisplatin (60 mg/m2) was administered over 24 h as a continuous intravenous infusion in combination with infusional high-dose prochlorperazine. Antiemetic efficacy in the first trial was assessed in terms of the number of episodes of nausea, retching, and/or emesis during the 24 h following cisplatin administration. The pharmacokinetics of high-dose prochlorperazine were evaluated in eight patients treated in study 2 at the two dose levels below those at which dose-limiting toxicity was noted. RESULTS: The maximally tolerated dose of prochlorperazine in combination with cisplatin (60 mg/m2 administered as a continuous infusion over 24 h) was 24 mg/h. The dose-limiting toxicity was grade 4 agitation and confusion noted in one patient treated at 26 mg/h. This patient died 3 days following cessation of chemotherapy due to the toxicity of the regimen in combination with the debilitating pulmonary effects of the disease. The mean end of infusion prochlorperazine level at the 24 mg/h dose level was 1.1 microM, a concentration previously reported to be consistent with the reversal of the multidrug resistance phenotype. Two partial responses were observed in study 2. CONCLUSIONS: We conclude that the antiemetic efficacy of high-dose infusional prochlorperazine does not appear to be improved over more convenient bolus administration. However, prochlorperazine levels consistent with those required in vitro for drug resistance reversal are attainable within the dose range having a tolerable toxicity profile.

Adult↗
PubMed2001

Initial pathological events in renal dysplasia with urinary tract obstruction in utero.

Multicystic dysplastic kidneys (MCDK) and obstructive renal dysplasia (ORD) are two different phenotypes of dysplasia commonly associated with urinary tract obstruction. However, the mechanisms whereby obstruction in the developing kidney leads to each dysplasia are unknown. In the present study, 16 fetal MCDKs and 3 fetal ORDs (18-35 weeks of gestation) were analyzed with light microscopy, point-counting morphometry, immunohistochemistry with a podocyte marker, and scanning electron microscopy. Additionally, reconstructions of dysplastic nephrons were done via serial section analysis. Early stages of MCDK and ORD similarly revealed numerous cyst formations, predominantly in the subcapsular nephrogenic zone. Occasionally, glomerular tuft remnants with mature podocyte phenotypes were observed in cysts, suggesting the acquisition of filtration. Three dimensionally, basic nephron structures were installed in the cystic nephrons, namely the macula densa with a primary loop structure. Cysts developed in the once-induced nephrons due to fluid retention in both MCDK and ORD. In utero urinary tract obstruction may cause urine retention in functioning nephrons and lead to glomerular cysts in the nephrogenic zone. These findings were common to MCDK and ORD, albeit at different sites of obstruction. Expansion of glomerular cysts with tubular dilatation (cysts) disturbs the subsequent nephrogenesis and may contribute to the misdevelopment of fetal kidneys.

Cysts↗
PubMed2001

An ultrastructural study of osteoclasts and chondroclasts in poorly calcified mandible induced by high doses of strontium diet to fetal mice.

A high dose strontium diet was fed to fetal mice from day 1 of gestation to birth in order to investigate the ultrastructural changes of osteoclasts/chondroclasts when associated with poorly calcified bone/cartilage. Calcification in the mandibular bone and condylar cartilage was extensively inhibited by this diet. Multinucleated osteoclasts and chondroclasts were observed on the mandibular alveolar bone and in the resorption area of the condylar cartilage, respectively. However, both cell types never formed ruffled borders and clear zones at the cell surfaces facing the matrices indicative of bone resorption, although they had well-developed organelles and vacuoles. Furthermore, they revealed signs of phagocytosis of the matrix vesicles. These results indicate that osteoclasts/chondroclasts can exhibit phagocytotic activity in response to requirements.

Animals↗