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Biomedical subjects

K Takaya

Publications and source records attributed to K Takaya.

At least 55 records · Page 3Linked to original sources

Resetting of parathyroid hormone secretion after vitamin D3 treatment in hypoparathyroidism and after parathyroid adenectomy in primary hyperparathyroidism.

The relationship between parathyroid hormone (PTH) secretion and extracellular calcium (Ca) level is reciprocal causality. The equilibrium operating point determines basal PTH secretion rate and basal extracellular Ca level. We studied how this equilibrium was achieved in the subjects with decreased PTH secretion or decreased parathyroid glands number. Basal/maximum ratio of serum PTH, which reflects the basal secretory state of parathyroid glands, was increased in 9 hypoparathyroid patients treated with vitamin D3 (VD3) [7 patients with idiopathic hypoparathyroidism] and in seven of nine parathyroid adenectomized patients. There was a negative correlation between the ratio and basal serum Ca level in the patients with IHP after VD3 treatment (r = 0.7167, P < 0.05) and in the patients after parathyroid adenectomy (r = 0.7760, P < 0.05). The regression curves in these two groups coincided regardless of the difference in maximum PTH secretion rate, which suggested that the basal secretory state of parathyroid glands was determined by extracellular Ca level in a similar manner in these subjects. There was a sigmoidal relationship between basal/maximum ratio of serum PTH and basal serum Ca level, when the data were collected from 15 hypoparathyroid patients before or after VD3 treatment, 9 parathyroid adenectomized patients, and 10 normal subjects (r = 0.9057, P < 0.001). This sigmoidal curve is thought to represent the fundamental relationship between the basal secretory state of parathyroid glands and extracellular Ca level.

Adenoma↗

Cerebral MRI and spectroscopy in Sjögren-Larsson syndrome: case report.

We report MRI and MRS of the brain in a patient with Sjögren-Larsson syndrome (SLS) in whom fatty alcohol oxidoreductase (FAO) deficiency has been verified. MRI showed periventricular lesions, high intensity on T2-weighted and low intensity on T1-weighted images at trigones of the lateral ventricles. 1H-MRS of these lesions revealed high lipid and low N-acetyl aspartate peaks. We presume such lipids in periventricular lesions with high T2 signal may be pathognomonic of SLS.

Adult↗

Augmented expression of the endothelin-A receptor gene in cultured mesangial cells from stroke-prone spontaneously hypertensive rats.

1. To elucidate the role of endothelin (ET) receptor in hypertension, we studied the expression of the ET-A receptor (ET-AR) gene and the ET-B receptor (ET-BR) gene in cultured mesangial cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. 2. The mesangial cells from both SHRSP and WKY expressed ET-AR predominantly. The level of the ET-AR mRNA in mesangial cells from SHRSP was 5-fold higher than that in the cells from WKY. The ET-BR mRNA in the mesangial cells from both strains was hardly detectable by northern blot analysis. 3. These results demonstrate that the expression of the ET-AR gene was markedly augmented in mesangial cells from SHRSP.

Animals↗

Endothelin-induced activation of mitogen-activated protein kinases in glomerular mesangial cells from normotensive and stroke-prone spontaneously hypertensive rats.

1. Kinase assay in myelin basic protein (MBP) containing polyacrylamide gels revealed that endothelin-1 (ET-1) and ET-3 increased MBP kinase activities in glomerular mesangial cells (MC) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rat (SHRSP). ET-1 stimulated MBP kinase activities more potently than ET-3. 2. Immunoprecipitation with anti-41-kDa MAPK antiserum showed that the MBP kinases activated by ET-1 correspond to 43- and 41-kDa MAPK. 3. Since Phorbol 12-myristate 13-acetate, a direct activator of protein kinase C, also activated MAPK, protein kinase C was suggested to mediate ET-induced activation of MAPK. 4. These results suggest that MAPK may mediate the ET actions in glomerular mesangial cells from normotensive rats as well as spontaneously hypertensive rats. Since ET is produced by vascular endothelial cells of the kidney and glomerular mesangial cells, the ET signalling pathway may have some physiological and pathophysiological significance in vivo glomerulus.

Animals↗

[Measurement of total body and leg bone mineral densities by dual energy X-ray absorptiometry in severely handicapped children and adults].

Total body and leg bone mineral densities (BMD) were measured in 42 severely handicapped children and adults using a dual energy X-ray absorptiometry (DEXA) (LUNAR Radiation Corp., DPX). Despite the differences in motor ability and nursing history, about 95% of patients, except for 2 cases, were diagnosed as having osteopenia. The degree of osteopenia was dependent on the motor disabilities of their original disease. Therefore we should bear in mind a precaution and therapy from early period. Because BMD of the legs in females were less than -3 SD of the age-matched control values, we should be careful for a possible fracture of femur. Since X-ray hazard of DEXA for patients is considerable to be negligible, this will provide an effective means for quantifying bone mineral in severely handicapped patients.

Absorptiometry, Photon↗

[Metabolic and functional magnetic resonance imaging of the brain: clinical application to pediatric brain diseases].

We have developed 1H-chemical shift imaging (CSI) and functional magnetic resonance imaging (FMRI) methods on a clinical MRI system, in which metabolic and functional information can be obtained from the brain. 31P- and 1H-CSI are in clinical use. Using 1H-CSI, the peaks of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) are clearly detected in multiple small voxels. In normal children, the ratio of NAA/Cho increased after birth in different manners in different parts of the brain. The peak of NAA decreased in some disorders with brain damage or neuronal immaturity. It has been shown recently that functional activation of the cortex can be visualized with MR imaging with a blood oxygen level dependent (BOLD) effect. At an activated area, the ratio of deoxyhemoglobin to oxyhemoglobin decreased in the capillary and venous beds. Therefore, with a decrease of the effect of the T2 susceptibility from deoxyhemoglobin, the signal intensity of the activated area increased. CSI and FMRI have a unique possibility in the field of non-invasive brain analysis.

Adolescent↗

Cis elements for transcriptional regulation of the human endothelin-A receptor gene.

To elucidate the transcriptional regulation of the endothelin-A receptor (ET-AR) gene, we defined the cis elements in the 5'-flanking region by functional analysis. Chimeric gene constructs were prepared using serial deletion mutants of a 5-kilobase (kb) fragment of the human ET-AR 5'-flanking region and the luciferase gene and were transfected into a rat vascular smooth-muscle cell line, A7r5. Deletion of the region between -2.0 kb and -857 bases caused a twofold increase in luciferase activity, and deletion from -137 bases to -53 bases reduced the activity by 50%. These results indicate the existence of a negative regulatory element and a positive regulatory element, respectively. The gel shift assay revealed the existence of nuclear proteins in A7r5 cells that bind to the region containing the positive regulatory element. Thus, we identified cis regulatory elements and nuclear factors that regulate the expression of the ET-AR gene.

Animals↗

Multiple transcripts of human endothelin-A receptor gene detected by reverse transcription and the polymerase chain reaction.

To elucidate the regulatory mechanism of gene expression of the human endothelin-A receptor (hET-AR), we characterized the hET-AR transcripts using reverse transcription (RT) and polymerase chain reaction (PCR) analysis in a variety of human tissues. The RT-PCR using a set of primers in exons 2 and 5 showed two lower-molecular-weight transcripts in addition to the expected fragment. PCR cloning of these two novel transcripts revealed that these transcripts contain a 199-base pair (bp) and a 327-bp deletion compared with the previously described hET-AR cDNA, respectively. Comparison of their sequences with that of the hET-AR gene showed that the lacking sequences exactly correspond to exon 4 and exons 3 and 4, respectively, suggesting that these lower-molecular-weight ET-AR transcripts may result from alternative RNA splicing. Therefore, we isolated the cDNAs of novel transcripts of hET-AR that might be generated by alternative RNA splicing. These results suggest that the alternative RNA splicing might contribute to the regulation of ET-AR gene expression.

Base Sequence↗

The time course of renal function and bone turnover in parathyroid crisis due to intratumoral hemorrhage.

Parathyroid crisis occurring in primary hyperparathyroidism is characterized by extremely high circulating levels of parathyroid hormone and acute onset of severe hypercalcemia. We describe a 62-year-old woman with parathyroid crisis probably due to an intratumoral hemorrhage. Renal dysfunction reduced the effectiveness of preoperative management and continued to deteriorate for 5 days after parathyroidectomy. The normalization of serum calcium after parathyroidectomy delayed and it took 6 days. Maintenance of renal function is important for pre- and postoperative courses of the present case. The rapid decrease in serum parathyroid hormone after parathyroidectomy was followed by a rapid and transient (about fivefold) increase in serum alkaline phosphatase with peak value on the 10th postoperative day. This indicated that reversal phase from bone resorption (accelerated by parathyroid hormone) to bone formation lasted about 10 days under the conditions of the present case.

Acute Disease↗

Molecular cloning of hamster brain and atrial natriuretic peptide cDNAs. Cardiomyopathic hamsters are useful models for brain and atrial natriuretic peptides.

Brain and atrial natriuretic peptides (BNP and ANP) are cardiac hormones with diuretic, natriuretic, and vasodilatory activities. Cardiomyopathic hamsters are widely used animal models of heart failure. Due to the structural divergence of BNP among species, examination on pathophysiological roles of BNP using cardiomyopathic hamsters is so far impossible. We therefore isolated hamster BNP and ANP cDNAs, and investigated synthesis and secretion of these peptides in normal and cardiomyopathic hamsters. The COOH-terminal 32-residue peptide of cloned hamster preproBNP with 122 amino acids, preceded by a single arginine residue, supposedly represents hamster BNP showing < 50% homology to rat BNP. Alpha-hamster ANP, 28-residue peptide, is identical to alpha-rat ANP. In hamsters, BNP and ANP occur mainly in the ventricle and the atrium, respectively. The 32-wk-old hypertrophic cardiomyopathic BIO14.6 strain exhibited ventricular hypertrophy. The 32-wk-old dilated cardiomyopathic BIO53.58 strain remained at the stage without apparent heart failure. In BIO14.6 and BIO53.58 strains at this age, ventricular BNP and ANP gene expressions are augmented, and the plasma BNP concentration is elevated to 136 and 108 fmol/ml, respectively, three times greater than the elevated plasma ANP concentration, which well mimics changes of the plasma BNP and ANP concentrations in human heart failure. Cardiomyopathic hamsters, therefore, are useful models to investigate the implication of BNP in human cardiovascular diseases.

Amino Acid Sequence↗

The human endothelin-B receptor gene. Structural organization and chromosomal assignment.

The gene encoding the human endothelin-B receptor (hET-BR) has been isolated, and its structural organization and chromosomal assignment have been determined. Southern blot analysis demonstrated a single copy of the hET-BR gene in the human genome. The hET-BR gene spans 24 kilobases and consists of seven exons and six introns. The size range for exons is 109-2855 base pairs, although that for introns is 0.2-14.5 kilobases. Every intron occurs near the border of the putative transmembrane domain in the coding region. The major transcription initiation sites were mapped to the positions 258 and 229 base pairs upstream of the ATG initiation codon by primer extension and nuclease S1 protection experiments. The 5'-flanking region of the hET-BR gene lacks conventional TATA and CCAAT boxes but contains a sequence of potential Sp1 binding sites upstream of the transcription initiation sites. There are some canonical consensus sequences of cis-elements including GATA motif, acute phase reactant regulatory element, and E box. Using human-rodent somatic hybrid cell lines, the hET-BR gene was assigned to human chromosome 13. The present study will lead to a better understanding of the mechanism for the transcriptional regulation of the hET-BR gene and will give a clue as to how to search for possible genetic disorders of hET-BR.

Amino Acid Sequence↗

Induction of discriminant function concerning postoperative local recurrence or distant metastasis in 589 patients with differentiated thyroid cancer.

For the purpose of predicting postoperative local recurrence and/or distant metastasis in differentiated thyroid cancer, a discriminant analysis was done. To assess the reliability of this method and the induced function, simulation was done by using random samples under various conditions. Simulation revealed that the results obtained by this method were relatively stable. The discriminant functions Z1 and Z2 were induced, which are required at many hospitals. If the ratio of recurrence is less than 1:8 in a hospital, function Z1 should be applied. If the ratio is 1:10, function Z2 should be applied. Z1 = -(sex x 2.104) + (age x 0.032) - (diameter of tumor x 0.033)-(site of tumor x 0.871) - (histology x 0.393) + 0.249 (discriminant boundary 0.451) Z2 = -(sex x 1.967) + (age x 0.018) + (diameter of tumor x 0.025) - (site of tumor x 0.646) + (histology x 0.014) - (local invasion x 0.840) - (lymph node metastasis x 0.009) + (operation x 0.364) - (lymph node dissection x 0.235) + 1.058 (discriminant boundary 0.400). In an internal check, sensitivity was 78%, specificity 64%; and false-negative rate 5%. In an external check, sensitivity was 68%, specificity 93%, and false-negative rate 9%. In the actual application to hospitals, sensitivity was 58% to 100%, specificity 47% to 63%, and false-negative rate 0% to 16%. In clinical usage, a high sensitivity and low false-negative rate are required. These results fulfilled this condition.

Adenocarcinoma, Follicular↗

[Intensive chemotherapy for alveolar soft part sarcoma with lung metastasis in a child].

Alveolar soft part sarcoma (ASPS) is one of the soft tissue sarcomas characterized by metastasis early in the course of the disease, regardless of slow tumor growth. The ultimate clinical outcome is, therefore, very poor. To date, the efficacy of combination chemotherapy for this tumor has not been confirmed. We present a case of ASPS in an 8-year-old boy with bilateral pulmonary metastasis who received systemic combination chemotherapy (CPM/IFO/ACD/ADR/CD DP/VP-16 as induction, and VCR/ACD as maintenance therapy) for eleven months. The result showed that despite the prevention of tumor progression, such intensive chemotherapy could not cure the disease. Besides refinement of chemotherapy regimens, immunotherapy might be considered for ASPS.

Antineoplastic Combined Chemotherapy Protocols↗

The enveloping of intercellular collagenous fibrils by reticular cell processes in postnatal development of rat lymph nodes.

In the lymph nodes of adult rats reticular fibers are known to be covered by the processes of reticular cells. This study aims to visualize the sequence of the envelopment of reticular fibers by reticular cells during development. Rat popliteal lymph nodes of one to twenty-three days after birth were examined by electron microscopy. At the earliest stages, collagenous protofibrils were found in the intercellular space between studded mesenchymal cells. The protofibrils clustered around the plasma membrane of immature reticular cells and then became arranged into microfibrils of 30-40 nm in diameter. Bundles of the fibrils which might be called reticular fibers were surrounded by processes of more than one reticular cell. Then the reticular fiber came to be enclosed by the cytoplasmic process of a single reticular cell. Finally at 16-23 days after birth, the reticular fiber was completely ensheathed by the thick cytoplasmic process of a single reticular cell closed with a junctional complex. Throughout these periods, basal lamina-like materials existed between the reticular fiber and cytoplasmic process. Clumps of fibrils were rarely in contact with leukocytes, including lymphocytes. Immature elastic fibers appeared among collagenous fibrils of the reticular fiber when the fiber came to be enclosed by processes of some reticular cells. It was shown that the enclosure of the reticular fiber by the reticular cell did not result from physical pressure due to the increase of the number of lymphocytes, but the reticular cell actively enclosed the reticular fiber.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Recombinant human granulocyte-colony stimulating factor (rhG-CSF) treatment for spleen abscess and periostitis in a patient with chronic granulomatous disease].

A 9-year-old boy with chronic granulomatous disease was hospitalized on May, 1991, because of continued fever and pain in the right elbow. Increased bone intensity at the distal end of right humerus on x-ray and a 33 x 36 mm space-occupying lesion in the spleen on abdominal CT scan were recognized. Under a diagnosis of periosteitis and spleen abscess, intravenous infusion of rhG-CSF at a dose of 200 micrograms/m2/day was started in combination with antimicrobial therapy. Fever, tenderness, swelling in the right elbow and inflammatory indices improved three weeks after the institution of therapy. Hydrogen peroxide (H2O2) formation by neutrophil increased significantly, although intermittently, during the therapy. The spleen abscess had completely vanished on CT scan on February, 1992. The therapy was well tolerated and no significant side effects were observed. The use of rhG-CSF in combination with potent antibiotics is recommended for patients with serious infections in chronic granulomatous disease to avoid a fatal course.

Abscess↗

[Is the new WHO's histological typing clinically useful for the diagnosis of follicular cancer of the thyroid?].

We tried to re-diagnose our 57 cases of thyroid follicular cancer between 1965 and 1988 in accordance with Histological Typing of Thyroid Tumours published by WHO in 1988. 1) The incidence of follicular cancer in differentiated cancers was decreased from 17.9% to 8.3% (26 cases). The number of widely invasive type and minimally invasive type was 13 cases equally. 2) Twenty four cases were diagnosed as papillary cancer. The reason was that 20 cases had a small focus of papillary structure, and other 4 cases had features of follicular variant type of papillary cancer. These 24 cases had good prognosis as our 262 cases of papillary cancer, in contrast to 26 cases of follicular cancer having worse prognosis. 3) The incidence of distant metastasis in follicular carcinoma was increased from 28.1% to 42.3%; 23.9% in minimally invasive type and 61.5% in widely invasive type, respectively. New WHO classification is acceptable according to this clinical study of our cases. We would have to treat more aggressively the patient diagnosed follicular cancer by WHO classification because of high incidence of distant metastasis.

Adenocarcinoma↗

Appearance of the reticular cells which trap antigens in the rat lymph node in postnatal development.

The cells binding and retaining immune complexes on their cell surface existed in rat lymph nodes with no germinal centers. This study attempted to clarify the relationship between the two types of cells, reticular cells and follicular dendritic cells (FDCs), in the rat lymph node at early stages of postnatal development by immuno-electron microscopy on anti-horseradish peroxidase (HRP) and HRP injected rat. On the 19th and 23rd day after birth, germinal centers were not yet constructed nor were typical FDCs visible. However, immune complex binding cells were observed on the 23rd day, and not on the 19th. HRP reactive materials (immune complexes) were localized between lymphocytes and large lucent cells, making meshworks. They were revealed by electron microscopy on the cell surface which invaginated into the cytoplasm. The HRP reactive cells extended their cytoplasmic processes and formed a connection by their processes. They were reticular cells which enclosed reticular fibers by their cytoplasmic processes or contacted with reticular fibers closely. The reticular cells may be precursors of the FDCs.

Animals↗

Familial mental retardation associated with balanced chromosome rearrangement rcp t(8;11)(q24.3;p15.1).

We report three sisters and their father with a reciprocal balanced translocation, rcp t(8;11)(q24.3;p15.1) and the same abnormal phenotypes, including mental retardation, growth disturbance, and amblyopia. It is considered that the abnormal phenotypes in our four cases might result from a tiny deletion or gene mutation at the breakpoints in 8q or 11p or both. Our cases showed no resemblance, apart from mental retardation, to Langer-Giedion syndrome, which is caused by the deletion of 8q23.3 and 8q24. Furthermore, our patients did not have the cardinal features of Beckwith-Wiedermann syndrome or WAGR which are caused by deletion of 11p. It is suggested that the amblyopia in our four cases might have resulted from the breakpoints at 11p15.1.

Adult↗