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Biomedical subjects

M Noda

Publications and source records attributed to M Noda.

At least 523 records · Page 29Linked to original sources

Transcriptional regulation of osteocalcin production by transforming growth factor-beta in rat osteoblast-like cells.

Osteocalcin (OC) is one of the abundant non-collagenous bone matrix proteins produced exclusively by osteoblasts, and its serum level is used as an indicator of bone metabolism in patients. Transforming growth factor-beta (TGF beta) is abundant in bones and platelets, promotes wound healing in vivo, and is a potent stimulator of the production of extracellular matrix proteins in fibroblasts and osteoblasts. The effects of TGF beta on OC gene expression were examined in rat osteoblast-like cells, ROS17/2.8. TGF beta 1 decreased OC levels in the culture media 2- to 3-fold. TGF beta 1 also decreased the level of osteocalcin mRNA about 3-fold in a dose-dependent manner. TGF beta 2 and TGF beta 1,2 a heterodimeric form, showed similar effects on OC mRNA levels as TGF beta 1. The suppression of the OC message level was detectable at 24 h and lasted for up to 72 h. This effect on OC mRNA was blocked by cycloheximide. The stability of OC mRNA was not changed by TGF beta 1. On the other hand, the rate of OC gene transcription was reduced 4- to 5-fold, as estimated by in vitro nuclear transcription (run-on) assay. TGF beta 1 blocked the increase in the OC mRNA level induced by PTH or 1,25-dihydroxyvitamin D3. These results indicate that TGF beta inhibits osteocalcin gene expression at least in part through transcriptional control.

Animals↗

In vivo stimulation of bone formation by transforming growth factor-beta.

The effect of transforming growth factor-beta (TGF beta) on bone in vivo was examined. Twelve daily injections of 1 microgram TGF beta directly onto the periostea of parietal bones of neonatal rats stimulated the formation of periosteal woven bone. The thickness of the treated parietal bones increased at least 2-fold in a dose-dependent manner. This TGF beta effect was localized at the sites of injection, and no change was observed in contralateral parietal bones and tibiae. The body weight in these growing rats was not affected by TGF beta 1. TGF beta 2 had effects similar to those of TGF beta 1 on the parietal bones in vivo. These results reveal for the first time that TGF beta stimulates bone formation in vivo and indicate its anabolic role in local bone metabolism.

Animals↗

Type beta transforming growth factor regulates expression of genes encoding bone matrix proteins.

TGF beta modulates the growth and differentiation of various cell types, in part by regulating the production of extracellular matrix proteins. In rat osteoblast-like cells TGF beta stimulates the production of collagen, osteopontin and osteonectin. On the other hand, TGF beta inhibits the production of osteocalcin, one of the most abundant non-collagenous bone matrix proteins, which is only expressed in osteoblasts. Inhibition of osteocalcin expression by TGF beta in the rat osteoblastic osteosarcoma, ROS 17/2.8 cells, occurs at least in part through transcriptional control.

Animals↗

[Conscious survey of dental patients. 1. Questionnaire related to general dentistry (in the case of the new patients of the Nippon Dental University Hospital)].

Increased information on dentistry in the mass media in recent years may have caused changes in patients' attitudes toward dental care. To better understand patient' attitudes, we conducted a questionnaire survey of patients on the first visit to our hospital. Of 384 responses, 196 were eligible for statistical analysis. The following findings were obtained. 1. Among the motives for visiting a dental clinic, "Manifestation of pain or symptoms" was given by majority (85.7%) of respondents, followed by "detection of abnormality" (20.4%). The percentage of patients wanting treatment of "any part suggested by the dentist" was highest (35.7%), followed by those expecting "treatment including cleaning" (30.1%). The above results indicate that patients still tend to visit a clinical after subjective symptoms appear and leave the content of treatment to the dentist. However, an increasing number of patients appear to be concerned with their oral condition and visit a clinic before manifestation of symptoms. 2. Among factors in selecting their dentist, "expertise" obtained the highest percentage, 87.2%, followed by "providing prompt treatment" (38.8%) and "trying to avoid pain" (32.1%), in that order. Dissatisfaction with dentists was described as "no explanation of treatment" in 57.1%, "lack of sympathetic attitude" in 38.3% and "easily resorts to tooth extraction" in 35.4%. These results suggest that patients expect good human relations with their dentists, sufficient explanations of treatments and sympathetic consideration, as well as expertise. 3. The majority of patients (85.7%) hoped to receive instructions on oral hygiene and to be increased interest in information above prophylaxis. Meeting their needs will remain a future issue for dentists.

Attitude to Health↗

[Conscious survey of dental patients. 2. Questionnaire related to prevention (in the case of the new patients of the Nippon Dental University Hospital)].

A questionnaire on the consciousness of new patients was conducted in Nippon Dental University Hospital. Following our prior report, items regarding dental prevention were asked to 196 subjects in the present case. The results are as follows. 1. 53.1% of the subjects had experienced scaling of the teeth. However only 15.4% of them had regularly scaling. 2. 62.8% of the subjects had been given guidance in brushing and 39.8% of them had used toothbrushes by themselves in the guidance. 3. 99.5% of the subjects brushed their teeth everyday. 58.5% of them brushed twice a day. Regarding the brushing period, "3 minutes" amounded the highest radio, 33.3%. 4. Regarding the major purpose of brushing, "prevention of oral diseases" amounted to 50.5%, followed by "unknown". Namely, 23.0% of the subjects had no definite purpose of brushing. This figure suggests that the awareness on brushing was unexpectedly low. 5. 85.7% of the subjects wanted to have oral sanitation guidance and oral health management. Among them. 59.5% wanted to have "regular examination". To the question "How often can you visit our hospital except treatment?", 48.2% of the subjects answered "twice or more per year", 41.1% "a day for each examination" and 53.6% answered "60 minutes per day". Among those who wanted to have oral sanitation guidance and oral health management, only 32.7% wanted to participate in our oral sanitation class. These results indicate that many patients want to have passive management but for would start action by themselves. Thus it is the most important for dentists to carry out sufficient education and guidance under these situations.

Attitude to Health↗

Transformation suppressor genes.

Flat revertants with reduced malignancy in vivo can be isolated from Kirsten sarcoma virus-transformed NIH3T3 cells following transfection with a normal human fibroblast cDNA expression library. We have recovered from one such revertant a 1.8 kb cDNA clone, "Krev-1", that possesses revertant-inducing activity in transfection assay. The Krev-1 cDNA has the capacity to encode a protein with a calculated molecular weight of 21,000 having strong structural similarity to ras proteins (ca. 50% homology), especially in their GTP/GDP-binding, effector-binding and membrane attachment domains. Point-mutations of Krev-1 protein at the 12th and the 59th amino acid positions from the aminoterminus potentiated the transformation suppressor activity by 2-5 times, and point-mutations within the putative effector-binding domain and at the C-terminal acylation site reduced the activity.

Amino Acid Sequence↗

[A resected case of hepatocellular carcinoma effectively treated by hepatic artery embolization and systemic chemotherapy].

A 64-year-old male complaining of abdominal fullness was admitted to hospital for close examination. Hepatocellular carcinoma was diagnosed by various imaging techniques and the patient was treated by 3 transarterial embolizations and 2 courses of systemic chemotherapy with CDDP. The tumor was reduced and the effect was judged to be a partial response to these therapies. By resection, a residual mass had histologically no live cancer cells. This case was considered to have had a complete response with multidisciplinary treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[Confidence region of alveolar bone level on xeroradiography].

Dental radiographs can be important for examination, evaluation and diagnosis of periodontal disease, and they have been widely used by dentists. However, discrepancies between radiographs and existing clinical periodontal tissue have been found. The purpose of this study was to investigate the relationship between the existing alveolar bone level on a Xeroradiograph and the root surface area covered with a periodontal ligament. Alveolar bone blocks from human skulls (total 34 teeth) and 60 patients (total 165 teeth) were used for this study. Each human skull bone block was taken Xeroradiograph under three types of conditions. 165 teeth from patients with severe periodontal disease were taken Xeroradiograph by a parallel method. The following equation was used for measuring the teeth on the Xeroradiograph. alpha = Root area supporting the existing alveolar bone/Root area from periapical to C-E junction x 100 The root surface area of each of the teeth extracted from bone blocks and of the extracted teeth from patients were measured by the membrane technique and calculated as follows: beta = Root surface area covered with periodontal ligament/Root surface area x 100 There was no significant difference in equation alpha calculated on three types of Xeroradiographs in the human skull. Significant positive correlations between alpha and beta were obtained, and an empirical regression line was constructed to estimate the ratio of the root surface area covered with periodontal ligament from the existing alveolar bone level on the Xeroradiograph. The results suggest that the ratio of the area of periodontal ligament to the root surface area given by these methods provides useful data for examination, diagnosis and evaluation of periodontal disease.

Alveolar Process↗

[CT appearance of uterine adenomyosis].

CT findings in 37 cases with pathological diagnosis of uterine adenomyosis were reviewed retrospectively. The attenuation coefficient of adenomyosis is almost same as normal parenchyma on both plain and enhanced CT. The margin was obscure except for one case. In focal type, deviation of the endometrium and deformity of the uterus may be a clue to the detection of adenomyosis. But differential diagnosis of adenomyosis from leiomyoma with ill-defined margin was very difficult. In diffuse type, the uterine body is swollen without deviation of the endometrium. This type can be diagnosed if the endometrium identified clearly.

Adult↗

Carcinoid tumors of the gallbladder with adenocarcinomatous differentiation: a morphologic and immunohistochemical study.

Two patients with gallbladder carcinoid tumors with adenocarcinomatous differentiation were examined. In both cases, the tumor contained argyrophilic granules and alcian blue-positive mucin. One contained argentaffin granules and the other showed PAS-positive mucin. Numerous membrane-bound electron-dense neurosecretory granules were demonstrated by ultrastructural study. Immunohistochemistry applied for the tumors clarified the epithelial, hormonal, and metaplastic character. Epithelial tumor markers, i.e., carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA), were positive in these tumors. The neuroendocrine nature was demonstrated by positive results of chromogranin A and neuron-specific enolase (NSE). Hormonal activities were not confirmed in the tumor cells. These results suggested that carcinoid tumors in the gallbladder have a multidirectional differentiation represented by a morphological continuum ranging from carcinoid to adenocarcinoma.

Adenocarcinoma↗

[Antigen presentation in pulmonary tuberculosis].

Antigen presenting capacity (APCC) by monocytes (Mono) and alveolar macrophages (AM), using PPD as the antigen, was determined in 15 patients with pulmonary tuberculosis and 9 healthy controls who all showed positive PPD skin tests. Results were as follows: 1) Mono from both healthy controls and tuberculosis showed APCC to autologous peripheral T lymphocytes, and no significant difference was observed between the two groups. 2) AM from tuberculosis showed APCC to autologous peripheral T lymphocytes, however AM from healthy controls did not. 3) APCC by autologous Mono or AM to lung T-lymphocytes was lower than that to peripheral T-lymphocytes, but the difference was not significant. 4) In tuberculosis, APCC, observed before chemotherapy, was remarkably weakened during the first two months of therapy, and almost recovered to the previous level thereafter. 5) The mechanism which enhances APCC by AM in tuberculosis is uncertain. But neither increased DR antigen expression on AM nor release of IL-1 from AM suggested to be be responsible for the enhanced APCC in tuberculosis.

Adult↗

Cyclic AMP-mediated stabilization of osteocalcin mRNA in rat osteoblast-like cells treated with parathyroid hormone.

Osteocalcin (bone gamma-carboxyglutamic acid-containing protein) is exclusively produced by osteoblasts, which are the major target cells of parathyroid hormone (PTH) in bone. This study examined the effect of human (h) PTH(1-34) on osteocalcin gene expression in the rat osteoblast-like osteosarcoma cells ROS17/2.8. hPTH(1-34) increased in a dose-dependent manner the steady state levels of osteocalcin mRNA 2- to 3-fold with an ED50 of about 5 X 10(-10) M. This effect was detectable at 12 h, peaked at 24 h, and lasted at least up to 48 h. Forskolin, cyclic 8-bromo-AMP, isobutylmethylxanthine, cholera toxin, and (-)-isoproterenol similarly elevated osteocalcin mRNA. hPTH(1-34) did not alter the transcriptional rate of the osteocalcin gene, estimated by nuclear run-on assays, but increased the stability of osteocalcin mRNA. hPTH(1-34) also increased 2- to 3-fold the osteocalcin level in the culture media determined by radioimmunoassay. PTH, thus, promoted osteocalcin gene expression in these cells at least in part through mRNA stabilization via cyclic AMP mediation, a mechanism known only in few systems.

1-Methyl-3-isobutylxanthine↗

Sensitive determination of diazepam and N-desmethyldiazepam in human material using capillary gas chromatography-mass spectrometry.

A reliable and sensitive capillary gas chromatographic-mass spectrometric method was developed for the detection and determination of diazepam and its major metabolite, N-desmethyldiazepam, in human material. Medazepam served as the internal standard. Quantitative determination was achieved using mass fragmentography with selected ions of m/z 256 for diazepam and m/z 242 for N-desmethyldiazepam and medazepam. The limit of detection was 1 ng/g and the recoveries were 98.54 +/- 3.95% for diazepam and 98.66 +/- 6.48% for N-desmethyldiazepam. The calibration graph was linear over the concentration range from 1.0 ng/g to 1.0 microgram/g for diazepam and N-desmethyldiazepam. Using this method, trace amounts of diazepam and N-desmethyldiazepam were detected in the tissues of an autopsied individual.

Aged↗

Transcriptional regulation of osteopontin production in rat osteosarcoma cells by type beta transforming growth factor.

Type beta transforming growth factor (TGF beta) was shown to regulate the production of several extracellular matrix proteins. Osteopontin (OP) is a recently discovered bone matrix protein which was shown to promote the attachment of osteoblastic rat osteosarcoma ROS 17/2.8 cells to their substrate. We examined the effects of TGF beta on OP production and OP mRNA in ROS 17/2.8 cells. Four-day treatment with 4 ng/ml TGF beta 1 increased substantially the level of osteopontin in the cell culture media, as estimated by immunoblotting. Metabolic labeling showed that this effect was associated with a 3-4-fold increase in OP biosynthesis. TGF beta 1 also increased, in a dose-dependent manner starting at 0.4 ng/ml, the steady-state level of OP mRNA. The increase in OP mRNA was first detected 48 h after the addition of TGF beta 1 and lasted at least until 120 h. The half-life of OP mRNA, estimated in the presence of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, was about 10 h and was not altered by TGF beta 1. On the other hand, the increase in OP mRNA was blocked by actinomycin D. Nuclear run-on assays indicated that TGF beta 1 increased the rate of transcription of the OP gene. Examination of hormonal interactions showed that TGF beta 1 opposed or compensated for the reduction in OP mRNA produced by dexamethasone and that TGF beta 1 did not further augment OP mRNA levels which had been increased by 1,25-dihydroxyvitamin D3 treatment. TGF beta 2 had similar effects on OP gene expression as TGF beta 1. In conclusion, TGF beta promotes the production of osteopontin in the osteoblastic osteosarcoma cells through a pathway which is at least in part mediated by transcriptional events.

Animals↗

Effect of fibroblast-derived differentiation inducing factor on the differentiation of human monocytoid and myeloid leukemia cell lines.

A fibroblast-derived differentiation inducing factor (F-DIF) purified from medium conditioned by a human fibroblast cell line (WI-26VA4) induced differentiation of human monocytic leukemia cell lines (U-937, THP-1) into cells with macrophage characteristics. F-DIF alone induced the differentiation of ML-1 cells only marginally, but it synergistically increased the differentiation when combined with TNF. Interferon-gamma, tumor necrosis factor, GM-CSF, interleukin-1 and interlukin-4 synergistically enhanced the differentiation of U-937 cells when combined with F-DIF.

Cell Differentiation↗

Possible involvement of two signaling pathways in induction of neuron-associated properties by v-Ha-ras gene in PC12 cells.

Harvey sarcoma virus induces a number of neuron-associated properties in a nerve growth factor-responsive cell line, PC12 (Noda, M., Ko, M., Ogura, A., Liu, D., Amano, T., Takano, T., and Ikawa, Y. (1985) Nature 318, 73-75). We investigated the mechanism of this phenomenon using PC12 sublines cotransfected with a plasmid containing v-Ha-ras gene under control of a hormone-responsive enhancer/promoter element of the mouse mammary tumor virus long terminal repeat (pM14-1) and a plasmid encoding G418 resistance (pSV2neo). Extent of the expression of neuron-associated properties in several cell clones after the addition of dexamethazone (DEX) seems to correlate well with the levels of the v-Ha-ras gene expression. After the induction of v-Ha-ras expression with DEX in these cell lines, sustained elevation of the levels of cAMP as well as of phosphatidylinositol (PtdIns) metabolites, inositol trisphosphate, and diacylglycerol, is observed. Physiological significance of this phenomenon is confirmed by the observation that dibutyryl cAMP and phorbol-12-myristate 13-acetate synergistically induces the expression of neuron-associated properties in PC12 cells. In control PC12 sublines transfected with pSV2neo alone, DEX shows no effects on their cell morphology and the levels of cAMP and the PtdIns metabolites, although these control cell lines are competent to the effects of dibutyryl cAMP and phorbol ester. The priming activity known to be associated with nerve growth factor is also observed with v-Ha-ras as well as with dibutyryl cAMP plus phorbol ester but not with dibutyryl cAMP or phorbol ester alone. The observations suggest that the role of v-Ha-ras gene product in this system may involved simultaneous activation of the two signaling pathways, those mediated by cAMP and by PtdIns turnover.

Acetylcholinesterase↗