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Biomedical subjects

M Takakura

Publications and source records attributed to M Takakura.

51 records · Page 3Linked to original sources

Telomerase activity in human endometrium.

Human uterine endometrium undergoes a complex pattern of changes in proliferation and secretory activity during the menstrual cycle. In the present study, telomerase activity in normal endometrium was examined using a non-radioisotope PCR-based telomeric repeat amplification protocol assay. Various levels of telomerase activity were detected in the 60 normal endometrial samples examined, depending on the phase of the menstrual cycle. Of 21 proliferative-phase endometrial samples, 20 (95%) expressed telomerase activity, whereas 8 of 19 (42%) secretory-phase or menstrual endometrial samples did (P = 0.002). Five of nine (56%) samples from atrophic endometrium from postmenopausal women also expressed telomerase activity. Eleven of 21 (52%) endometrial samples in the proliferative phase expressed high telomerase activity detectable after 100-fold dilution of extracts, whereas none of the 19 endometrial samples from the secretory phase or during menstruation and none of the 9 postmenopausal endometrial samples did (P < 0.001). The highest activity was observed in the late proliferative phase, but activity dramatically decreased with the progression of the secretory phase. Surprisingly, the levels of telomerase activity detected in the late proliferative phase were comparable to those detected in the endometrial cancers examined. Immunohistochemical analysis of the expression of proliferating cell nuclear antigen revealed that telomerase activity is closely correlated with endometrial cell proliferative activity. These findings indicate that normal endometrium expresses telomerase, the activity of which changes dramatically over the course of the menstrual cycle, suggesting in turn that telomerase is a regulated enzyme linked to cellular proliferation and that hormone functions may be involved in its regulation.

Biomarkers↗

[Survey on oral health of university students: examination on tooth conditions using panoramic X-ray films].

As an aid in instructions oral health care to university students, tooth conditions were examined using panoramic X-ray films. The materials were taken from 129 students of the University of Tokyo. The average age was 22 years 5 months. The results were as follows: 1. Lack of tooth was frequently found to be both maxillary and mandibular third molars. It was also occasionally found to be maxillary first premolars, mandibular lateral incisors, and mandibular second premolars. The average value for lack of tooth per individual was 0.9. 2. Root canal fillings were often found in mandibular first molars, maxillary central incisors, mandibular second molars and maxillary second premolars. The average value was 1.1. 3. Metal restorations were often made in first and second molars, especially in mandibular. The average value was 6.2. 4. As for maxillary third molar axis, the majority showed normal direction. In mandible, however, the normal direction was only found in 37.7% and the others showed troublesome axes. It seemed that careful attention should be given to the mandibular third molar conditions.

Adult↗

[Prevalence of depressive symptoms and its relation to demographic variables in high school students].

In order to determine the prevalence of depressive symptoms and to examine its relationship to demographic variables in late adolescents, questionnaires were administered on 3,254 high school students in Okinawa. Depressive symptoms were assessed using the Zung Self-rating Depression Scale (SDS). The results were as follows: The SDS score distribution curve was near-normal. The mean SDS scores of males and females were 40.4 and 41.7, respectively. Overall, 53.4% of males and 61.4% of females had depressive symptomatology according to an SDS cut-off point of 40 or greater. There were significant differences in mean SDS scores and prevalence by gender. Females had higher depressive symptom scores. Both indicators of depressive symptomatology were higher than those in U.S. adolescents and Japanese adults. When controlling for the effect of school type, both male and female students living in urban ureas of the main island had more depressive symptoms than students living in rural areas of remote islands. When controlling for the effect of region, female students attending vocational high schools showed more depressive symptoms than other high school students. However, there was no difference by school type among male students. The high prevalence of depressive symptoms suggests that it is necessary to modify the assessment cut-off point for high school students and to promote further school mental health care.

Adolescent↗

MCI-154 activates the Ca(2+)-activated K+ channel of vascular smooth muscle cells.

The aim of this study was to examine the effects of MCI-154, a new positive inotropic agent with vasodilating properties, on the Ca2+-activated K+ channel (KCa channel) of vascular smooth muscle cells. Cultured smooth muscle cells from a porcine coronary artery were studied using the patch-clamp technique. Extracellular application of 100 microM MCI-154 activated the KCa channel in intact cell-attached patch configurations. In excised inside-out patch configurations, application of 100 microM MCI-154 to the cytosolic side activated the KCa channel directly, suggesting that the Ca2+ sensitivity of the KCa channel itself is modulated. Though extracellular application of 100 microM amrinone, a phosphodiesterase inhibitor, activated the KCa channel in the cell-attached patch configurations, application of 100 microM amrinone to the cytosolic side could not activate the KCa channel in inside-out patch configurations. These results indicate that different from amrinone, MCI-154 can modulate Ca2+ sensitivity of the KCa channel in vascular smooth muscle cells.

Amrinone↗

[A study on physique, exercise frequency and physical strength of middle-aged forestry workers].

This study was conducted to compare physical strength, physique, exercise frequency and type of work of 4,334 male and 439 female middle-aged office and outdoor forestry workers. Both male and female outdoor workers were taller and had lower Broca's indices than their office counterparts, while the body weight of outdoor male workers was lighter and that of female outdoor workers heavier than those of male and female office workers, respectively. The number of outdoor workers not engaging in frequent exercise was found to be significantly greater than that of office workers. Male outdoor workers had significantly higher maximal oxygen uptake (cardio-respiratory endurance), grip strength (muscular strength) and standing trunk flexion (static flexibility) than the male office workers whereas the opposite was true for whole body reaction time (agility), eyes-closed one-leg balancing (static balance) and sit-ups (muscular endurance). Female outdoor workers had higher maximal oxygen uptake (cardio-respiratory endurance), grip strength (muscular strength) and standing trunk flexion (static flexibility) than the female office workers, whereas the opposite was the case for whole body reaction time (agility), eyes-closed one-leg balancing (static balance) and sit-ups (muscular endurance). All of these differences among females were significant except for maximal oxygen uptake (cardio-respiratory endurance). When indoor and outdoor workers of the same sex with similar physiques and exercise frequencies were compared male outdoor workers had higher maximal oxygen uptake (cardio-respiratory endurance) and greater standing trunk flexion (static flexibility) whereas female outdoor workers had greater grip strength (muscular strength) and standing trunk flexion (static flexibility). From these results, it was suggested that maximal oxygen uptake (cardio-respiratory endurance) and standing trunk flexion (static flexibility) in the male workers and grip strength (muscular strength) and standing trunk flexion (static flexibility) in the female workers were related to their working situations. Both the physical strength of workers and personal characteristics must be carefully considered in order to preserve the health of both indoor and outdoor forestry workers.

Adult↗

[Factorial construct validity of a measurement scale of fatigue in junior high school students].

To investigate factorial construct validity of a measurement scale of fatigue symptoms in junior high school students, a questionnaire which consisted of Cumulative Fatigue Symptoms Index (CFSI) and Psychological Condition Test (PCT) was administered on 289 students in Okinawa. Reliability coefficients were 0.607-0.811 for CFSI scales. A principal factor analysis with varimax rotation was applied to CFSI. In boys, 4 factors were extracted; general psychological symptoms, fatigue, emotional instability, and decreased morale and vitality. In girls, 4 factors were extracted; depression and anxiety, decreased morale and vitality, fatigue, and irritability. The same procedure was applied to PCT. In boys, 4 factors were extracted; negative feeling, vigor, inferiority complex, and fatigue. In girls, 4 factors were extracted; negative feeling, anger, vigor, and fatigue. Among factors derived from CFSI and PCT, the fatigue factor of CFSI was correlated with that of PCT. The factors concerning psychological symptoms of CFSI were correlated with those of PCT. However, the vigor factor of PCT was not correlated with any other factors. These results suggest that CFSI in junior high school students had factorial construct validity.

Adolescent↗

Normotensive glucocorticoid-suppressible hyperaldosteronism in adult.

A 40 year-old man was admitted to our hospital for detailed examination of hypokalemia (2.7 mEq/l). His blood pressure was normal. Metabolic alkalosis, ACTH dependent hyperaldosteronism (18 ng/dl) and over-response to synthetic ACTH were observed. Plasma renin activity, on the other hand, was within the normal range (1.7 ng/ml/hr). Serum potassium was normalized to 4.1 mEq/l and the responsiveness of the renin-angiotensin-aldosterone system was recovered after the administration of dexamethasone. These results led us to suggest that this case might be normotensive glucocorticoid-suppressible hyperaldosteronism. The etiology which was not associated with hypertension and low plasma renin activity has not been clarified but may be related to the shortness of duration of this disease. Our case was also afflicted with mild hypercortisolemia and excessive excretion of urinary 17-hydroxycorticosteroid and 17-ketosteroid which was suppressed by the administration of dexamethasone (2 mg/day). These findings may be related to hypersensitivity of the fascicular zone of the adrenal gland to ACTH.

17-Hydroxycorticosteroids↗

[Discrepancy in karyotypes between peripheral blood and bone marrow during blastic crisis in chronic myelocytic leukemia].

A 32-year-old female was diagnosed as having Ph1-positive chronic myelocytic leukemia (CML) on March 6, 1985. She was intermittently treated with busulfan or 6-mercaptopurine. Her regimen was changed on February 27, 1987 to interferon-alpha (HLBI, Sumitomo) because of leukocytosis (46,200/microliters) with basophilia (45%) and splenomegaly refractory to conventional therapy. She was admitted to our hospital on November 27, 1987 because of blastic crisis. Cytogenetic analysis on peripheral cells was repeated six times during the treatment with HLBI. The sixth analysis was done on bone marrow cells as well. Nineteen to 22 metaphases were analyzed by the trypsin G-banding method after short-term culture. Cytogenetic analysis of peripheral cells revealed 46, XX, Ph1 in 9% of metaphases and 47, XX, Ph1, +8, i(17q) in 91% on March 2, 1987, and 47, XX, Ph1, +8, i(17q) in 95.2% of metaphases and 48, XX, Ph1, +8, i(17q), +19 in 4.8% on December 11, 1987. Karyotypes of bone marrow cells on December 11, 1987 were 48, XX, Ph1, +8, +8, 4(17q) in 73.7% of metaphases and 47, XX, Ph1, +8, i(17q) in 26.3%. It was speculated that abnormal clones might have developed in other sites than bone marrow.

Adult↗

A case of calcitonin-producing parathyroid adenoma with primary hyperparathyroidism.

A 57-year-old female was admitted to our hospital with general lassitude, loss of appetite, nausea, upper abdominal pain, thirst, polydipsia and polyuria. On admission, she had an asymmetrical pear-shaped tumor in the right supraclavicular region and severe hypercalcemia. Plasma C-PTH was elevated to 22.72ng/ml. Plasma calcitonin was also elevated to 336 pg/ml. She died of respiratory and cardiac failure of two weeks after admission without any positive response to the treatment, including hemodialysis. Pathohistologically, the tumor was a parathyroid adenoma. The concentrations of C-PTH, intact PTH and calcitonin in the tumor tissue were markedly high: 4.56 micrograms/g wet, 13.9 ng/g wet and 50.7 ng/g wet, respectively. Immunohistologically, the tumor cells and the fibrous stroma were stained strongly positive to rabbit anti-human calcitonin antibody and rabbit anti-human N-PTH antibody by indirect immunoperoxidase staining. Calcitonin-producing tumors, except for medullary thyroid carcinoma are rarely reported. To our knowledge, this is the first report of such a calcitonin-producing parathyroid adenoma associated with primary hyperparathyroidism.

Adenoma↗

Chronic myelomonocytic leukemia with polyneuropathy and IgA-paraprotein.

A 65-year-old woman had chronic myelomonocytic leukemia with peripheral neuropathy and IgA paraprotein with kappa type light chain. Plasma cells with "flaming" cytoplasma were seen in the bone marrow specimens. The findings suggest that chronic myelomonocytic leukemia may involve B-lymphocytes in the proliferative process and that it may be a clonal disease. Moreover, this case was associated with peripheral sensori-motor polyneuropathy. The disorder was responsive to prednisolone, as oral administration of prednisolone improved not only the peripheral polyneuropathy, but also the hematological findings. Serum vitamin B12 and lysozyme in the serum and urine were decreased by the steroid therapy. The administration of prednisolone is effective not only for polyneuropathy but also chronic myelomonocytic leukemia.

Bone Marrow↗

FADD gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter to restrict induction of apoptosis to tumors in vitro and in vivo.

Gene transfer vectors will dramatically increase the safety and effectiveness of cancer gene therapy, if they could restrict expression of the therapeutic products to the target tumors. To realize such a tumor-targeting system, telomerase is one of the most promising candidates. It is because telomerase activity is detected in the vast majority of tumors, but not in most normal cells. Activation of telomerase is tightly regulated at the transcriptional level of the telomerase catalytic subunit (hTERT). Therefore, the use of the hTERT promoter-driven vector system could restrict the expression of therapeutic products to telomerase-positive tumors. In this study, we constructed the expression vector of FADD gene with death domain afforded by the hTERT promoter (hTERT/FADD) and investigated its effect on tumors in vitro and in vivo. Transient transfection with the hTERT/FADD construct induced apoptosis in telomerase-positive tumor cells of wide range. In contrast, normal fibroblast cells without telomerase did not undergo apoptosis following the hTERT/FADD transfer. Furthermore, the growth of subcutaneous tumors in nude mice was significantly suppressed by the intratumoral injection of the hTERT/FADD construct (every day for one week) compared to the control (P<0.0005). The findings described here indicate the high potentiality of a novel telomerase-specific gene therapy of tumors with telomerase.

Adaptor Proteins, Signal Transducing↗