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Biomedical subjects

A Miyauchi

Publications and source records attributed to A Miyauchi.

At least 109 records · Page 6Linked to original sources

Obvious mRNA and protein expression but absence of mutations of the RET proto-oncogene in parathyroid tumors.

The study on the expression of the RET proto-oncogene in parathyroid tumors disclosed obvious mRNA expression by the reverse transcription (RT)-polymerase chain reaction (PCR) method and protein expression by Western blotting. To find out whether mutations in the cysteine-rich regions or tyrosine kinase domain of the RET proto-oncogene are etiological for parathyroid tumorigenesis, sporadic parathyroid adenomas and carcinomas, parathyroid tumors from multiple endocrine neoplasia 1, familial isolated hyperparathyroidism or hereditary hyperparathyroidism-jaw tumor syndrome were screened by PCR-single strand conformation polymorphism and PCR restriction fragment length polymorphism. Missense mutations in the cysteine-rich region, or codons 768 or 918 in the tyrosine kinase domain of the RET proto-oncogene, were not detected in any of the examined cases of parathyroid tumors. These results suggest that mutations of the RET proto-oncogene do not represent a frequent mechanism of tumorigenesis for parathyroid tumors.

Adult↗

Primary intramedullary spinal cord germinoma. Case report.

Primary central nervous system germinoma usually presents as an extraaxial intracerebral mass. The authors report the rare occurrence of an intramedullary spinal cord germinoma at the conus medullaris in a 24-year-old man, which was treated by partial removal and radiation therapy. The tumor was highly radiosensitive and the patient remains disease free 15 months posttreatment.

Adult↗

Thymic nurse cells as the site of thymocyte apoptosis and apoptotic cell clearance in the thymus of cyclophosphamide-treated mice.

Structural changes in the thymus of BALB/c mice after the intraperitoneal injection with a single high dose (200 mg/kg) of cyclophosphamide (CY) were examined. A large number of thymic nurse cell (TNC)-like structures that contained apoptotic thymocytes were observed in the thymus between 8 and 20 hours after CY treatment, just before a marked reduction in the number and proportion of PNAhi, CD3-, CD4+ CD8+ thymocytes. The majority of apoptotic thymocyte-containing TNC-like structures had an epithelial nature and were mainly located in the subcapsular and outer cortex, perivascular area of the cortex, corticomedullary junction and, in part, in the medulla. Most thymocytes seemed to undergo apoptosis synchronously in every TNC-like structure, but one or two fully intact mature thymocytes were found in every one. By 24 hours after CY treatment, many vacuoles that contained apoptotic cells in various stages of degeneration were observed within the epithelium, and most of the apoptotic cells disappeared at 24 hours. We herein demonstrated that the epithelium of TNC-like structures had a phagocytic activity in the digestion of apoptotic thymocytes by the presence of phagolysosomes with acid phosphatase activity. The epithelium left very small vacuoles with a small amount of nondigestible dense granules. The minority of apoptotic thymocyte-containing TNC-like structures scattered in the entire cortex between 8 and 20 hours after CY treatment was macrophage (M phi)-derived. Many apoptotic cell-containing M phi were observed as early as 4 hours after the CY injection. Apoptotic thymocytes of CY-treated mice showed the internucleosomal DNA fragmentation. In conclusion, CY accelerates physiologic thymocyte apoptosis, and epithelial TNC are one of the principal sites of thymocyte apoptosis as well as an environment for the nursing of immature thymocytes. Both the epithelium of TNC and M phi participate in digestion of apoptotic cells and have the efficient capacity of clearance of apoptotic thymocytes in the normal thymus at a presumed high rate.

Animals↗

A comparison of the prevalence and risk factors of high blood pressure among Japanese living in Japan, Hawaii, and Los Angeles.

THE AUTHORS STUDIED THE PREVALENCE AND RISK FACTORS of hypertension in samples of 2053 Japanese ages 40 to 70 in Hiroshima, Hawaii, and Los Angeles. The prevalence of hypertension (systolic blood pressure greater than or equal to 140 mmHg, diastolic blood pressure greater than or equal to 90 mmHg, or receiving antihypertensive drug treatment) was higher in Hawaii and Los Angeles for both sexes and almost all ages than in Hiroshima. The age- and sex-adjusted prevalence of hypertension in Hawaii, Los Angeles, and Hiroshima was 42.6%, 37.2%, and 29.7%. Hypertension was associated with a significant elevation in serum glucose, insulin, triglyceride, and total cholesterol levels in the combined participant population of Hawaii, Los Angeles, and Hiroshima. Age- and sex-adjusted mean values of serum total cholesterol, triglyceride, and insulin were highest in Hawaii and lowest in Hiroshima. The mean body mass index and 2-hour serum glucose levels were greatest in Hawaii and equal in the two other cohorts. These results suggest that hyperinsulinemia and hyperlipidemia may explain the prevalence of hypertension in the research participants.

Adult↗

Transmenopausal change of trabecular bone density and structural pattern assessed by peripheral quantitative computed tomography in Japanese women.

Trabecular bone pattern, related to connectivity, was analyzed along with a separate measurement of cortical and trabecular bone mineral density (BMD) at the distal radius by peripheral quantitative computed tomography (pQCT) in 48 perimenopausal women, consisting of 25 premenopausal women aged 41 to 52 (mean 46.6 +/- 2.9 years) and 23 early postmenopausal women aged 46 to 59 (mean 53.2 +/- 3.2 years) within 5 years of the menopause (mean 2.7 +/- 1.5 years). No significant difference was found in either cortical or trabecular bone density between premenopausal and postmenopausal women despite a significant difference in age (premenopause vs postmenopausal: 46.7 +/- 2.9 years vs 53.2 +/- 3.1 years, p < 0.00001), including a slow change of BMD, if any, before and within 5 years of the menopause. However, analysis of trabecular fragments and perforation revealed a significant increase of the number of perforations in postmenopausal compared with premenopausal women (premenopausal vs postmenopausal: 0.9 +/- 1.6 vs 2.9 +/- 2.3, p < 0.002), indicating that disconnectivity has already increased before a significant reduction of BMD. Furthermore, chi-square analysis showed that even postmenopausal women with trabecular BMD more than 160 mg/cm3 were about 11 times more likely to have three or more perforations than premenopausal ones (odds ratio: 11.42, F = 0.030). These data suggest that trabecular bone connectivity is more sensitive that BMD in the detection of the early changes of postmenopausal osteoporosis.

Adult↗

Germline mutations of the RET proto-oncogene in eight Japanese patients with multiple endocrine neoplasia type 2A (MEN2A).

Multiple endocrine neoplasia type 2A (MEN2A) is a dominantly inherited cancer syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia. The gene responsible for MEN2A was localized by linkage analysis to chromosome 10q11.2 in 1987, and recently mutations in RET, a proto-oncogene in the candidate region, were discovered in patients with MEN. The majority of mutations found so far in MEN2A patients have been located in nucleotide sequences encoding cysteine residues in the extracellular domain of RET. To characterize MEN2A germline alterations in the Japanese population, we screened DNA from eight unrelated patients for mutations in exons 10 and 11 of the RET proto-oncogene and found mutations in all eight patients, at codons 618, 620, or 634; each of these sites encodes a cysteine residue in the extracellular domain of RET. The mutations were confirmed in other affected individuals in the respective families by digestion of polymerase chain reaction (PCR) products containing the mutated codons with restriction enzymes (Rs alpha I, CfoI, or AluI) for which cleavage sites had been generated by the specific genetic alteration. These PCR-restriction enzyme systems will be useful for genetic diagnosis in members of families carrying these mutations.

Base Sequence↗

Surgical treatment of an enormous aneurysmal portahepatic venous fistula: report of a case.

We report herein the case of a 20-year-old woman in whom an enormous aneurysmal portahepatic venous fistula was found. The portal aneurysm developed in the anterior inferior segment of the right hepatic lobe, and communicated with the right portal vein and the right hepatic vein. Due to the enormous size of the shunt, and because the patient's venous blood ammonia level increased by about twofold after eating, a right lobectomy of the liver was performed. A review of the available literature and a discussion of the most appropriate treatment follows the presentation of this case.

Adolescent↗

Accurate and simple method of diagnosing thyroid nodules the modified technique of ultrasound-guided fine needle aspiration biopsy.

We describe an accurate and simple method of diagnosing thyroid nodules by the modified technique of ultrasound-guided fine needle aspiration biopsy (UG-FNAB). An Aloka SSD 2000 focus type scanner (Aloka Co., Tokyo, Japan) equipped with a 10-MHz mechanical sector probe and a 7.5-MHz convex probe was used. First, a clear picture of the thyroid gland was taken with the use of the 10-MHz probe to determine the abnormalities. Then, a 7.5-MHz probe (1.5 x 0.8 cm of surface area) was used to guide the needle perpendicularly to the neck. This method enabled us to obtain samples from nodules greater than 5 mm. We applied this technique to 1000 patients who had uncertain diagnosis by the conventional method of FNAB. The advantages of this method are as follows: (i) The use of a small probe (7.5 MHz) is most important, since a needle can be inserted by watching the monitor without an assistant. (ii) The biopsy site can be chosen precisely. (iii) Small thyroid cancers, i.e., 5 mm cancer, can be biopsied without any difficulty. (iv) A life-threatening anaplastic carcinoma can be diagnosed at an early stage. (v) An intraglandular metastasis to the opposite lobe can be detected. (vi) Cystic carcinoma, difficult to diagnose by FNAB, can be diagnosed accurately. This method is highly recommended for all clinicians who are currently doing FNAB.

Biopsy, Needle↗

Regulation of the plasminogen activator/plasmin system by epidermal growth factor in cultured human endometrial cells.

Recent studies have suggested that epidermal growth factor (EGF) and plasminogen activators (PA) are involved in the implantation of concepti. Therefore we attempted to evaluate the effect of EGF on the release of PA in primary cultures of human endometrial cells. The addition of EGF to culture medium increased the release of tissue-type PA (t-PA). The effect of EGF was significant at 5 ng/ml, which produced a 45% increase in t-PA release. EGF also stimulated the release of urokinase-type PA (u-PA), as well as the release of PA inhibitor type 1 (PAI-1). These stimulatory effects on the release of t-PA and PAI-1, but not of u-PA, were enhanced by the concomitant addition of progesterone. The modulatory effect of EGF on PA release seemed to be selective in that other growth factors, such as basic fibroblast growth factor, transforming growth factor beta and interleukin-1 beta, did not affect the release of PA. From these data, we propose that EGF in concert with progesterone participates in embryo implantation, the process entailing tissue remodelling and cell migration in part by modulating the PA/plasmin system.

Cells, Cultured↗

Prostate cancer-induced oncogenic hypophosphatemic osteomalacia.

A 65-year-old male with prostate carcinoma showed mild hypocalcemia of 7.9 mg/dl, marked hypophosphatemia of 1.7 mg/dl, hyperphosphaturia (tubular reabsorption of phosphorus 43% and tubular threshold for phosphorus of 0.6 mg/dl), low serum 1,25 (OH)2D level of less than 5 pg/ml and osteomalacia indicated by a marked increase of relative osteoid volume and fractional formation rate in the undecalcified section. Oncogenic osteomalacia due to prostatic carcinoma with suppression of 1,25 (OH)2D production and phosphaturia was suggested.

Adenocarcinoma↗

Tumor-specific mutations in the tyrosine kinase domain of the RET proto-oncogene in pheochromocytomas of sporadic type.

Sporadic pheochromocytomas, sporadic medullary thyroid carcinomas (MTCs), pheochromocytomas and/or MTCs in multiple endocrine neoplasia (MEN) 2A or 2B were screened for mutations in the tyrosine kinase domain of the RET proto-oncogene by direct sequencing of PCR-amplified products or sequencing subcloned DNAs from PCR-products. All tumors of 4 MEN 2B patients were confirmed to contain a heterozygous missense mutation at codon 918 (ATG-->ACG; Met-->Thr) of the RET proto-oncogene as well as their leukocytes. The same tumor-specific mutations at codon 918 were also found in 5/16 (31%) sporadic pheochromocytomas. These results suggest that mutations of the RET proto-oncogene in its tyrosine kinase domain play a role not only as the predisposing gene for MEN 2B, but also as a tumorigenic factor for pheochromocytomas of sporadic type.

Adolescent↗

Effects of steroid hormones on fibrinolytic system in cultured human endometrial cells.

In a primary human endometrial cell culture, the addition of progesterone resulted in an approximately 2-fold increase in the amount of tissue-type plasminogen activator (t-PA) released into the culture media, with the minimal effective dose being 10(-7) M. In contrast, progesterone significantly reduced the release of urokinase-type PA (u-PA). Endometrial cells are known to release a major PA inhibitor, PAI-1. Progesterone stimulated the release of PAI-1. These observed effects of progesterone seem to be mediated through the progestin receptor in that R5020, a specific ligand for progestin receptor, mimicked the effects of progesterone, and RU486, an antagonist of progesterone, completely eliminated the effects of progesterone. It is notable that estradiol, when added alone or in combination with progesterone, caused no discernible effect on the release of PAs and PAI-1. These results suggest that progesterone is a key hormone in regulating the PA/plasmin system in the human endometrium, thereby playing a pivotal role in implantation and ensuing embryonal development.

Cells, Cultured↗

Effect of calcium supplementation on bone density and parathyroid function in elderly subjects.

The effect of calcium supplementation on secondary hyperparathyroidism of old age depends on the intestinal absorption of the calcium preparation used. In order to test the bioavailability and clinical usefulness of a new calcium preparation, heated oyster shell-seaweed calcium (HOSS Ca), a randomized, prospective, double-blind comparison of HOSS Ca, calcium carbonate and placebo was carried out in 58 hospitalized women with a mean age of 82. Group A received 900 mg Ca/day Ca as HOSS Ca, group B 900 mg Ca/day as CaCO3 and group C placebo in addition to the basic hospital diet containing approximately 600 mg Ca/day. After 18 months, lumbar spine bone mineral density (BMD) measured by DPX was 106.1 +/- 3.5% (mean +/- SEM) of the pretrial basal value in group A, 99.8 +/- 3.8% in group B and 90.9 +/- 3.4% in group C (A bu not B significantly higher than C). Midradial BMD measured by DPX was 99.3 +/- 1.3% in A, 94.8 +/- 4.0% in B and 85.5 +/- 6.2% in C. The ratio of whole body calcium content between the 12th and 18th month was 96.5 +/- 1.7% in A, 90.1 +/- 2.7% in B and 89.8 +/- 1.3% in C (A but not B significantly smaller than C). Final/baseline ratio of urinary Ca/creatinine was 91.7 +/- 11.1 in A, 111.4 +/- 18.9 in B and 125.2 +/- 12.6 in C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Persistent expression of proto-oncogene c-fos stimulates osteoclast differentiation.

We analyzed c-fos mRNA expression by northern blotting analysis in chicken osteoclast precursors which spontaneously differentiate to multinucleated osteoclasts in 5-6 days. Osteoclast precursors as well as mature multinucleated osteoclasts showed constitutive expression of c-fos mRNA which is not found in osteoblasts. The c-fos expression was enhanced transiently by serum, dibutyryl cAMP (10(-4) M) and phorbol 12-myristate 13-acetate (TPA) (5 x 10(-7) M). To clarify the role of c-fos in osteoclast differentiation, c-fos DNA was transfected into osteoclast precursors. Greater than 2 fold increases in tartrate resistant acid phosphatase (TRAP) and bone resorptive activity were observed in the transfected cells compared to controls 3 days after transfection, suggesting that prolonged expression of c-fos caused enhanced osteoclast differentiation.

Acid Phosphatase↗

Ansa-recurrent nerve anastomosis for vocal cord paralysis due to mediastinal lesions.

Recurrent laryngeal or vagus nerve injuries in the mediastinum are repaired rarely because of technical difficulties. Impairment in phonation is especially severe in patients with respiratory dysfunction. We performed a simple and less invasive reconstruction, ansa cervicalis-recurrent laryngeal nerve anastomosis in the neck, to improve phonation in 2 patients. Although the reinnervated vocal cord did not regain normal movement, both of the patients obtained excellent improvement in phonation.

Aged↗

Carboxyl-terminal parathyroid hormone fragments stimulate osteoclast-like cell formation and osteoclastic activity.

The controversy still exists about the biological activity of carboxyl (C)-terminal PTH fragments. The present study was performed to examine the effect of C-terminal PTH fragments on osteoclast-like cell formation and bone-resorbing activity. In contrast to human (h) PTH-(1-34) or hPTH-(1-84), any C-terminal fragments examined [hPTH-(35-84), hPTH-(53-84), and hPTH-(69-84)] did not affect cellular cAMP production and intracellular calcium in osteoblastic UMR-106 cells. Although hPTH-(1-84) caused an increase in cAMP production and intracellular calcium less effectively than hPTH-(1-34) in UMR-106 cells, the former caused a stimulation of osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures more effectively than the latter. All of the C-terminal fragments significantly stimulated osteoclast-like cell formation, and their effectiveness seemed to depend on the amino acid length of the fragments. The conditioned medium from UMR-106 cells pretreated with C-terminal PTH as well as amino-terminal PTH significantly stimulated osteoclast-like cell formation from mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. Moreover, all of the C-terminal fragments stimulated osteoclast-like cell formation from hemopoietic blast cells even in the absence of osteoblasts, and their effectiveness seemed to depend on the length of fragments. As for bone-resorbing activity by mature osteoclasts, all of the C-terminal fragments stimulated bone resorption in osteoblast-containing mouse bone cell cultures, whereas these fragments did not affect the bone-resorbing activity of isolated rabbit osteoclasts. The present study first indicates that C-terminal PTH fragments stimulate osteoclast-like cell formation as well as bone-resorbing activity by mature osteoclasts in the presence of osteoblasts and accelerate osteoclast-like cell formation from hemopoietic blast cells in the absence of osteoblasts.

Animals↗