[Perioperative anesthetic management in neurosurgery].
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Anesthesia, General↗
Biomedical subjects
H Harada
Publications and source records attributed to H Harada.
FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development.
FGF receptor 2 isoform IIIb (FGFR2b), originally discovered as a receptor for FGF7, is known to be an important receptor in vertebrate morphogenesis, because FGFR2b null mice exhibit agenesis or dysgenesis of various organs, which undergo budding and branching morphogenesis. Since FGF7 null mice do not exhibit marked defects in organogenesis, it has been considered that other FGF(s) than FGF7 might function as a major ligand for FGFR2b during organogenesis. One of the candidate ligands is FGF10, because FGF10 binds to FGFR2b with high affinity and the formation of the limb and lung is arrested in FGF10 null mice as found in FGFR2b-deficient mice. Previous analyses of FGF10 null mice revealed that FGF10 is required for limb and lung development. To elucidate the role of FGF10 in wide-range organogenesis, we further analyzed the phenotypes of the FGF10 knockout mice. We found diverse phenotypes closely related to those for FGFR2b-deficient mice, which includes the absence of thyroid, pituitary, and salivary glands, while minor defects were observed in the formation of teeth, kidneys, hair follicles, and digestive organs. These results suggest that FGF10 acts as a major ligand for FGFR2b in mouse multi-organ development.
Animals↗
Effects of physostigmine and calcium on acetylcholine efflux from the hippocampus of freely moving rats as determined by in vivo microdialysis and a radioimmunoassay.
The effects varying the concentration of Ca2+ in perfused artificial cerebrospinal fluid ([Ca2+]csf) on basal acetylcholine (ACh) efflux from the hippocampus of freely moving rats, in the presence and absence of the cholinesterase (ChE) inhibitor physostigmine, were investigated using in vivo microdialysis and a highly specific radioimmunoassay for ACh. In the absence of physostigmine, basal ACh efflux was 3.4+/-0.7 pg/30 min (mean +/- SEM) at [Ca2+]csf = 1.26 mM. Stepwise increases in [Ca2+]csf elicited a gradual increase in ACh efflux that was significant at [Ca2+]csf = 5.04 mM. Inhibition of ChE by addition of 10 microM physostigmine to the perfusate increased the efflux of ACh to 103.2+/-21.1 pg/30 min ([Ca2+]csf = 1.26 mM), and the efflux was augmented still further by increasing [Ca2+]csf, a change that became significant at [Ca2+]csf = 3.78. These results illustrate the sensitivity of basal ACh efflux from the hippocampus to changes in the extracellular Ca2+ concentration, and suggest that a more accurate picture of hippocampal cholinergic activity is obtained by microdialysis using normal artificial cerebrospinal fluid, under physiological conditions, rather than in the presence of a ChE inhibitor.
Acetylcholine↗
Peroxiredoxin I expression in oral cancer: a potential new tumor marker.
This study investigates the applicability of the novel antioxidant protein, peroxiredoxin (Prx) I as a marker for tumor status in oral squamous cell carcinoma (SCC). Samples from 53 patients with SCC in the oral cavity were examined by immunohistochemistry. Correlations between the expression level of Prx I and proliferating cell nuclear antigen (PCNA), the clinical features of tumors, and their histopathological classifications were statistically analyzed. Cases exhibiting low Prx I expression level included significantly more with larger tumor mass cases (T-category, P=0.004), positive lymph node metastasis (N-category, P=0.015), advanced stage (P=0.002), and poorly differentiated cells (P=0.020). There was no significant difference between Prx I expression and the other indices.
Adult↗
Cbfa1, an essential transcription factor for bone formation, is expressed in testis from the same promoter used in bone.
Cbfa1 is an essential transcription factor for bone formation, but its transcripts have also been detected in thymus and testis. To elucidate the expression of Cbfa1 in testis, we isolated Cbfa1 cDNA from mouse testis. First we examined the length of the transcripts expressed in mouse testis by Northern hybridization. Using a cDNA probe that can detect both Type-I and Type-II Cbfa1 (Type-I: originally reported as Pebp2alphaA by Ogawa et al.; Type-II: originally reported as til-1 by Stewart et al.), 1.8-kb transcripts were detected in testis, and larger transcripts (6.3 kb and 7.4 kb) in T-cell lines, thymus and bone. Using a Type-II specific probe (bone isoform-specific probe), surprisingly, 1.8-kb testis transcript(s) were detected as well as those (6.3 kb) found in bone. In addition, the transcription start site in mouse testis coincides with one of three start sites identified in bone. These results suggest that the testis transcript is generated from the same promoter of Type-II Cbfa1, which is thought to be active only in osteoblasts and some chondrocytes. Next, to define the difference in length of transcripts, we isolated the Cbfa1 cDNA from mouse testis. Sequence analysis of the cDNA showed that alternative splicing around exon 2 and poly-adenylation within exon 8 occurred in the testis isoform, which produce the smaller transcripts. These data revealed that testis Cbfa1 mRNA is transcribed from same promoter used in bones, but the post-transcriptional regulation is different between testis and skeletal tissues.
Animals↗
Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis.
To clarify the role of the H-Ras in vivo, we generated H-ras null mutant mice by gene targeting. In spite of the importance of the Ras in cell proliferation and differentiation, H-ras null mutant mice grew normally and were fertile. The oldest H-ras mutant mice grew to be more than 30 months old. We used the H-ras deficient mice to study the importance of the H-ras and other ras genes in the development of skin tumors induced by initiation with 7, 12-dimethylbenz(a)anthracene (DMBA) followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). We showed that H-ras null mutant mice develop approximately six times less papillomas compared with wild-type littermates after 20 weeks of TPA treatment. While all papillomas examined (17 out of 17) in wild-type mice have mutations of H-ras at codon 61, 13 (62%) out of 21 papillomas in H-ras null mutant mice have mutations of K-ras gene at codon 12, 13, or 61 and another eight (38%) papillomas have no mutations in these codons of K-ras or N-ras genes. This suggests that the activation of H-ras gene is critical in the wild-type mice, but the activation of K-ras gene can replace the H-ras activation in the initiation step of skin tumor development in the H-ras deficient mice. Oncogene (2000).
Animals↗
Enhancement of cerebral cortical acetylcholine release by intraperitoneal acetic acid and its suppression by analgesics in freely moving rats.
Several lines of evidence suggest that central cholinergic neurons play a key role in the perception and control of pain. We investigated the effects of analgesics on the increase in central cholinergic activity and writhing responses elicited by i.p. injection of acetic acid. ACh efflux from the rat cerebral cortex and hippocampus was measured in the absence of a cholinesterase inhibitor using an in vivo microdialysis technique and a highly sensitive and specific radioimmunoassay. ACh efflux from the cerebral cortex was significantly increased during the first 30 min after acetic acid injection and then returned to the control levels. In contrast, acetic acid-induced writhing responses, indicative of the perception of pain, persisted for almost the entire 120 min observation period. No changes in ACh efflux were observed in the hippocampus. The centrally-acting analgesic morphine and the peripherally-acting analgesic indomethacin each completely abolished the enhanced cerebral cortical ACh efflux and the writhing, whereas diazepam, a muscle relaxant, selectively suppressed only the writhing. These results demonstrate that peripheral nociceptive stimulation transiently increases cholinergic activity in the cerebral cortex, but not in the hippocampus, and that analgesics suppress both the enhanced ACh efflux and the writhing induced by acetic acid.
Acetic Acid↗
A functional and quantitative mutational analysis of p53 mutations in yeast indicates strand biases and different roles of mutations in DMBA- and BBN-induced tumors in rats
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Journal Article↗
Clinical improvement following interferon-alpha alone as an initial treatment in CIDP.
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Adult↗
High-grade adenoid cystic carcinoma originating from the lacrimal gland.
Among primary lacrimal gland tumors, adenoid cystic carcinoma (ACC) is the most common malignant epithelial neoplasm; it is characterized by local intracranial invasion. A case with unusual dumbbell-type intracranial extension representing cavernous sinus syndrome is described. A 49-year-old woman was admitted to our hospital with right cavernous sinus syndrome. Computerized tomographic (CT) scans and magnetic resonance (MR) imaging demonstrated well-enhanced intraorbital and middle fossa tumors mimicking multifocal mass lesions. Operative findings revealed an ACC originating from the lacrimal gland and extending into the right cavernous sinus and middle fossa along the nerve sheath in the superior orbital fissure. Although MR image findings of intracranial ACC often resemble the image findings for meningiomas, intracranial ACC is very aggressive in comparison with meningioma. It is best treated surgically and aggressively.
Brain↗
Abortive alloantigen presentation by donor dendritic cells leads to donor-specific tolerance: a study with a preoperative CTLA4lg inoculation.
Donor dendritic cells (DCs) within allografts initiate the induction of an allospecific T cell response, while an abortive alloantigen presentation by DCs may induce allospecific unresponsiveness. We thus investigated the tolerogenic effect of donor DCs that were made incompetent in alloantigen presentation by treatment of CTLA4Ig. When we treated rats with donor DCs (2 x 10(6)/rat i.v.) on the preoperative day, nine rejected allografts in an accelerated manner (5.0 +/- 2.2 vs. 8.2 +/- 1.6 days in the control group). Preoperative inoculation of DCs pulsed with CTLA4Ig, a procedure which suppresses an allogeneic mixed lymphocyte reaction (MLR), also provoked an accelerated rejection (5.6 +/- 1.7 days). When DCs and CTLA4Ig (500 microg/rat i.p. on days -9, -7 and -5) were concomitantly inoculated, allograft survival was significantly prolonged (>38.7 +/- 40.0 days); a preoperative CTLA4Ig inoculation alone failed to do so (7.5 +/- 1.2 days). Long-term graft survivors tolerated skin grafts from the donor but not from those from a third party. These results indicate that abortive alloantigen presentation by donor DCs, upon which an accessory signal pathway is suppressed by CTLA4Ig, leads to prolonged graft survival and donor-specific tolerance.
Abatacept↗
Changes of liver fibrosis in chronic hepatitis C patients with no response to interferon-alpha therapy: including quantitative assessment by a morphometric method.
The aim of this study was to evaluate the antifibrotic effect of interferon (IFN)-alpha in chronic hepatitis C (CH-C) patients with no response to IFN-alpha therapy. We studied 76 patients (46 men, 30 women; mean age, 55.6 years) who received IFN-alpha intramuscularly, at a total close of 480 to 880MU for 6 months (group A). As a control group, we studied 50 patients (32 men and 18 women; mean age, 58.5 years) with CH-C who received medication other than IFN (ie, Strong-Neo-Minophagen C, ursodeoxycholic acid, and a herbal medicine, Sho-saiko-to [TJ-9]) and who had persistent alanine aminotransferase (ALT) elevation (group B). All patients were subdivided into three subgroups according to different patterns of ALT changes during the observation period, ie, (a) persistent ALT level < 60IU/ 1 (below about twice the upper limit of the normal range), (b) persistent ALT level > or = 60IU/1, (c) ALT levels other than (a) and (b). Liver biopsy was performed within 6 months prior to IFN therapy and more than 6 months after IFN therapy, while two liver biopsies were performed during therapy in group B. Liver fibrosis was compared between two specimens by staging. When the fibrosis stage was the same in the two specimens, we determined whether the fibrosis had improved or worsened by comparing the fibrotic ratio, ie, the ratio of the area of fibrosis to the area of the entire liver tissue specimen, calculated using computed graphic software. Serum aminoterminal peptide of type III procollagen (PIIIP) levels were measured on the day of the liver biopsy and their mean yearly changes were compared between the two groups. Improvement of liver fibrosis was found in 12% to 30% of patients in each ALT subgroup and in 24% of all patients in group A and there were no significant differences in liver fibrosis in comparison with findings in of group B when assessed by staging alone. However, these percentages rose to 59% to 75% and 66%, respectively, when liver fibrosis was assessed by the fibrotic ratio together with staging, resulting in a significant difference in fibrosis between groups A and B in total (P < 0.01). The mean yearly changes in serum PIIIP levels in each subgroup and in all patients in group A were below zero, indicating a tendency to improvement of fibrosis after IFN therapy, while these changes in group B were all above zero, except for subgroup (c). Improvement of fibrosis after IFN therapy was found in 15 of 24 patients (64%) whose ALT changes had the same pattern before and after IFN therapy, although no significant difference was noted between improved and worsened patients. These results suggest that IFN-alpha may have an antifibrotic effect even in CH-C patients with no overt response to IFN-alpha therapy, compared with the effect of medications other than IFN.
Alanine Transaminase↗
Clinical experience of pediatric kidney transplantation: what is the benefit?
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Adolescent↗
4-Nonylphenols and 4-tert-octylphenol in water and fish from rivers flowing into Lake Biwa.
Surveys of 4-nonylphenols (NOs) and 4-tert-octylphenol (OC) were performed for water and fish samples obtained from eight rivers flowing into Lake Biwa once every two months from April 1998 to March 1999. For water samples, NOs were detected all the year round (0.11-3.08 ng ml(-1)) at high frequency (48/48) in the eight rivers. OC was detected at lower concentrations (ND approximately 0.09 ng ml(-1)) and at lower frequency (23/48). The concentrations of NOs in the river water always showed minimum values at 5-8 degrees C in winter. It was presumed that the formation of NOs by the biotransformation of nonylphenol polyethoxylates decreased much in the sludge treatment of nonionic surfactants at the low temperature (5-8 degrees C) in winter. Average BCF values of NOs and OC in the six kinds of fish were calculated from the field data. The field BCF values of NOs 15-31 in the six kinds of fish were lower than the laboratory BCF values of 167 in Killifish and 282 in Salmon. For OC, the field BCF values 129-297 for the three kinds of fish were nearly equal to the laboratory BCF value, 261, in Killifish.
Animals↗
Importance of OGTT for diagnosing diabetes mellitus based on prevalence and incidence of retinopathy.
Study was made on the necessity and importance of the oral glucose tolerance test (OGTT) for diagnosing diabetes mellitus based on prevalence and incidence of diabetic retinopathy. Subjects were 12208 persons undergoing OGTT between 1965 and 1997. The prevalence of retinopathy was significantly elevated with FPG>/=126 and 2-h PG>/=198 mg/dl. The incidence of retinopathy was 15-30/10000 person-years (PY) with FPG<125, but with FPG of 126-139 it was significantly higher (69/10000 PY) and at 140-199 mg/dl it was elevated to 139/10000 PY. Subjects were classified at initial test into FPG<110, 110-125, 126-139, and >/=140 and further into 2-h PG<200 and >/=200 mg/dl for comparison with the incidence of retinopathy. Even with the same FPG, the incidence was two- to threefold higher with 2-h PG>/=200 mg/dl, indicating that 2-h PG was highly associated with the incidence of retinopathy. As for IFG, the prevalence of diabetes as defined by 2-h PG>/=200 in the OGTT increased with elevated FPG, and 33.7% of IFG cases showed 2-h PG>/=200 mg/dl. Based on the prevalence and incidence of retinopathy, we conclude that 126 mg/dl FPG is an appropriate cut-off level, and the OGTT is important for diagnosing mild diabetes mellitus.
Adolescent↗
Correlation among fasting plasma glucose, two-hour plasma glucose levels in OGTT and HbA1c.
A study was made on the association among 2-h plasma glucose (PG) in oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) using correlation and regression equation. Subjects were 13174 OGTT examinees tested between 1980 and 1998. Blood glucose was determined by the glucose oxidase method and glycated hemoglobin (HbA1c) by the HPLC method. As for correlation between 2-h PG and FPG, regression equation of the <60 year group was y=57.1+0.336x (r=0.866, P<0.0001) and that of the >==60 year group was y=61.5+0.286x (r=0.814, P<0. 0001). FPG was calculated at 124.3 in the <60 year group and 118.7 mg/dl in the >==60 year group for 2-h PG of 200 mg/dl, 2-h PG were calculated at 199.5 and 210.7 mg/dl for FPG of 126 mg/dl, respectively. In the <60 year group, FPG were calculated at 121.7 and 124.4 mg/dl and 2-h PG at 193.2 and 199.3 mg/dl for HbA1c of 6.0 and 6.1%, respectively. As for associations between HbA1c and FPG or 2-h PG being high correlation, it is possible to estimate a prevalence of DM in a group using HbA1c>==6.1%. High correlations were demonstrated among all the three measures; FPG, 2-h PG, HbA1c. If 2-h PG is used in diagnosing diabetes mellitus, an FPG of 126 mg/dl proposed by ADA and World Health Organization (WHO) as a diagnostic level of FPG is an acceptable value for the Japanese.
Adult↗
c-Abl expression in oral squamous cell carcinomas.
c-Abl is proto-oncogene product. c-Abl has roles in signal transduction, cell cycle regulation, and inhibition of apoptosis. There are many reports about c-Abl function in hematopoietic cells, but few are concerned with solid tumors. In the present study, biopsy specimens from 44 patients with oral squamous cell carcinomas were subjected to immunohistochemistry, and the expression levels of c-Abl were correlated with clinicopathological features. Statistical analyses revealed that c-Abl expression was significantly associated with T-category (p = 0.011), sex (p = 0.014), and differentiation (p = 0.007), but no significant difference was observed with N-category, age, primary tumor region, or the other histological gradings. The low c-Abl expression group included more T4, male, and poorly differentiated cases. There was a trend towards longer tendency survival in the high expression group, but the difference was not significant. We conclude that c-Abl is a good candidate for a tumor-expansion marker.
Adult↗
Cyclin D1 overexpression correlates with poor prognosis in patients with tongue squamous cell carcinoma.
Tongue squamous cell carcinoma makes up a large percentage of head and neck cancers, and the incidence among young patients is increasing. The aim of this study was to reveal the correlation between cyclin D1 (CCND1) expression and clinical and histologic features. We performed an immunohistochemical study on the level of CCND1 expression in tumor specimens obtained from 94 patients with tongue squamous cell carcinoma. The relationship between the expression and the following features such as age, sex, smoking and alcohol intake history, T, N, histologic grade, and multiple primary cancer was analyzed. Eighteen patients (19%) showed CCND1 overexpression (tumor cell nuclei positivity >/=50%). The 5-year survival rate of high CCND1 expressors was 39%, which was significantly poor (p=0.04). N classification correlated with CCND1 expression. CCND1 overexpression is associated with poor survival associated with progression of lymph node spread in patients with tongue squamous cell carcinomas. CCND1 expression may be a useful biologic marker for prognosis.
Adolescent↗