Experimental research on a fetal treatment for tetrahydrobiopterin deficiency.
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Adrenal Glands↗
Biomedical subjects
T Imamura
Publications and source records attributed to T Imamura.
Experimental research on a new treatment for maternal phenylketonuria(PKU).
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Animals↗
A mutation (Trp1193-->Leu1193) in the tyrosine kinase domain of the insulin receptor associated with type A syndrome of insulin resistance.
We evaluated a 35-year-old diabetic male patient with type A insulin resistance, showing acanthosis nigricans. Insulin binding to the patient's Epstein-Barr-virus transformed lymphocytes was mildly reduced. The maximal insulin-stimulated autophosphorylation of the insulin receptor from the patient's transformed lymphocytes was decreased to 45% of that from the control subjects. On examination, the biological activities of insulin and insulin-like growth factor I in the patient's cultured fibroblasts, insulin sensitivity of amino isobutyric acid uptake and thymidine incorporation was decreased, but insulin-like growth factor I action was normal. The sequence analysis of amplified genomic DNA revealed that the patient was heterozygous for a mutation substituting Leu for Trp at codon 1193 in exon 20 of the insulin receptor gene. The patient's mother and sister were also heterozygous for a mutation in the insulin receptor gene that substituted Leu for Trp1193 in the beta subunit of the receptor. Therefore, the mutation causes insulin resistance in a dominant fashion. They were less hyperglycaemic and more hyperinsulinaemic than the proband after glucose loading. The mother had diabetes mellitus but did not show acanthosis nigricans, while the sister did not have diabetes and showed acanthosis nigricans. These results suggest that this mutation causes defective tyrosine kinase activity of the insulin receptor, which results in insulin resistance. Insulin action and phenotypic appearance may be mediated by different factors.
Adult↗
Parachordoma: an ultrastructural and immunohistochemical study.
A case of parachordoma of the left calf in a 19-year-old Chinese female is reported. The tumour showed multinodular growth pattern and consisted of round or oval tumour cells with abundant eosinophilic cytoplasm and myxoid matrix. Tumour cells formed small nests and sometimes showed concentric arrangement. Physaliferous-like cells and undifferentiated spindle cells were occasionally observed among the cell nests. The myxoid matrix was positive for high-iron diamine stain, indicating the presence of chondroitin 4- and 6-sulphates and keratan sulphate. Ultrastructurally, well-developed rough endoplasmic reticulum, abundant intermediate filaments, microvillous cytoplasmic processes, pinocytic vesicles, and desmosome-like junctional structures were found. Tumour cells were positive for S-100 protein and vimentin, but negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and desmin. These results are consistent with the definition of parachordoma as a soft tissue neoplasm consisting of cells with histology and ultrastructure similar to those of chordoma cells but with immunohistochemistry similar to that of chondroid tumour cells.
Adult↗
Nuclear DNA content as a prognostic predictor in carcinoma of the pancreas.
Eighty-six patients with carcinoma of the pancreas were studied retrospectively. Paraffin-embedded specimens and flow cytometry were used to evaluate the accuracy of the measurement of nuclear DNA as a predictor of the postoperative prognosis. From the series of 86 patients, 72 with a diagnosis of tubular adenocarcinoma (Japanese classification) were selected, and their DNA ploidy pattern and clinical and pathological features were correlated; 52.3% of the 86 patients and 52.8% of the 72 tubular adenocarcinoma patients showed DNA aneuploidy. Histological examinations of the tubular adenocarcinomas showed 42.9% DNA aneuploidy in well differentiated, 56.8% in moderately differentiated, and 71.4% in poorly differentiated types. The DNA ploidy showed a statistically significant positive correlation with the T category. The presence or absence of retroperitoneal invasion was thought to be the most important prognostic factor. Cumulative survival rates showed that the prognosis for patients with retroperitoneal invasion and DNA aneuploidy was significantly worse than for those with DNA diploidy or those without retroperitoneal invasion.
Adenocarcinoma↗
Coronary-to-pulmonary artery shunts via the bronchial artery: analysis of cineangiographic studies.
Coronary-to-pulmonary artery shunts via the bronchial artery (CA-BA-PA shunts) were observed in 16 of 2,922 consecutive patients who underwent selective coronary cineangiography. Underlying diseases included Takayasu arteritis (n = 8), chronic pulmonary inflammatory diseases (n = 4), pulmonary thromboembolism (n = 2), pulmonary artery tumor (n = 1), and tetralogy of Fallot with pulmonary atresia (n = 1). Ventilation-perfusion scans were available in 15 of the 16 patients. Mismatched defects were identified in 11 patients, and matched defects were identified in four. Bronchial-to-pulmonary artery shunts were detected on selective bronchial angiograms and/or thoracic aortograms in 13 patients. Feeding arteries of the CA-BA-PA shunts included left atrial branches (n = 13), right sinus node branches (n = 7), left sinus node branches (n = 2), right conal branch (n = 1), left conal branch (n = 1), and posterolateral branches (n = 2). These coronary branches seemed to serve as collateral vessels from a coronary arterial system with a higher pressure to a pulmonary arterial system with a lower pressure in conditions of decreased pulmonary flow or in cases of chronic pulmonary inflammatory disease. The importance of the coronary artery along with other superior thoracic collateral networks in contributing to the development of shunts to the pulmonary artery is underscored.
Adult↗
Electrically stimulated contraction accelerates protein synthesis rates in adult feline cardiocytes.
Cardiocytes were induced to contract via electrical field stimulation with an 8 V/cm electrical square-wave pulse of 5 ms at 0.125-2.0 Hz for up to 6 h. Protein synthesis rates were measured as rate of incorporation of [3H]-phenylalanine into total cell protein. Rates of protein synthesis were accelerated 43 +/- 4%, P < 0.001, by 4 h. The acceleration of total protein synthesis showed a frequency dependence between 0.125 and 0.5 Hz. In addition to accelerating rates of total protein synthesis, electrical stimulation of contraction accelerated fractional rates of synthesis of myosin heavy chain by 42 +/- 8%, P < 0.05. Protein synthesis rates were not accelerated upon electrical stimulation using subthreshold voltages. Addition of 100 ng/ml of actinomycin D had no effect on the ability of electrical stimulation of contraction to accelerate protein synthesis. To uncouple excitation-contraction coupling, 2,3-butanedione monoxime (BDM) was used to block actin-myosin cross-bridge interactions. BDM significantly decreased the ability of electrical stimulation to accelerate protein synthesis rates.
Animals↗
[Anxiolytic activities of pentanthrene type heterocyclic compounds].
A series of pentanthrene type heterocyclic compounds were synthesized and evaluated for anxiolytic activities by three kinds of behavioral pharmacological tests. Several compounds showed anxiolytic activities. In particular, s-triazolo[3,4-a]phthalazine (Tri-P) and 3-propyl derivatives of Tri-P(PTP) showed remarkable activities, although the activities were slightly lower than those of diazepam. The results suggested that Tri-P or PTP is a useful lead compound for the development of the antianxietic agents. The relationship between the structure and anxiolytic activity, and the inducing mechanism of the activity was discussed.
Animals↗
Assessment of pulmonary artery pressure by pulsed Doppler echocardiography in patients with chronic pulmonary diseases.
Doppler echocardiography was recently developed for obtaining a flow velocity profile at any point in the cardiac chamber. A pulsed Doppler technique combined with cross sectional echocardiography was used to examine the flow velocity pattern in the right ventricular outflow tract in 32 patients with chronic pulmonary disease (CPD) and in 15 healthy subjects as controls. All patients underwent cardiac catheterization. Pulmonary flow velocity profiles in the right ventricular outflow tract were recorded simultaneously with electrocardiograms and pre-ejection periods (PEP), right ventricular ejection time (RVET), acceleration time (AT), and calculated PEP/RVET, AT/RVET were determined. All normal subjects had "dome-like" flow velocity patterns with a peak flow at the midsystole. In patients with CPD, there was a significant correlation between log10MPAP (mean pulmonary arterial pressure) and AT/RVET, the coefficient being r = -0.623, between PVR (pulmonary vascular resistance) and AT/RVET (r = -0.52), and between SVI (stroke volume index) and PEP (r = -0.645). Complications of pulmonary hypertension in CPD were relatively mild, but the pulsed Doppler technique was found useful for evaluating pulmonary arterial pressure and other right heart hemodynamics of CPD patients.
Adolescent↗
[Comparison of the gold wire electrode with cotton wick electrode for electroretinography in small laboratory animals].
Using the gold wire and cotton wick electrodes, the electroretinograms of mice and rats were measured, and then they were compared. The results obtained were as follows: 1) There were no remarkable differences in the latencies and amplitudes of a- and b-waves, amplitudes and numbers of waves of oscillatories between two different electrodes. 2) It was easy to make and maintain the gold wire electrode as compared with the cotton wick electrode. From these results, it appears that the gold wire electrode is useful for measuring the electroretinogram of small laboratory animals.
Animals↗
[Possibility of detecting visual functional disturbance in rats by the open-field test].
In order to determine whether visual disturbance in small rodents is detectable by means of the open-field test, the ambulation scores of enucleated and intact rats in an open-field were measured. In a 30-min test of Slc:Wistar/ST rats, there were significant differences in ambulation scores between enucleated and intact rats in the first 10-min. In addition, the effects of observation times (09:00-11:00, 13:00-15:00 and 17:00-19:00 hr) and strains on the open-field test were studied using a 10-min test. Regardless of observation times, ambulation scores of enucleated rats of the Slc:Wistar/ST and F344/N Slc strains were significantly elevated as compared with those of intact rats from both strains. When tested during the 13:00-15:00 hr period, there were significant differences in the Slc:SD rats. These findings indicate that the changes in ambulation are due to visual disturbance. However, significant ambulatory changes in F344/N Slc rats were documented at the three different observation times. Based on these results, Slc:Wistar/ST rats appear to be suitable for detecting visual disturbance by the open-field test.
Animals↗
[Visual evoked potential from dura in rats].
Visual evoked potentials (VEPs) were recorded from 8 different points (from points A and B near the bregma to points G and H near the occipital bone) of the dura under parietal bone in rats. The study was performed with 68 adult male Slc: Wistar/ST rats weighing 259.9-298.0g. VEPs recorded from the dura had a large negative component with a peak around 45 msec (N1), a large positive component with a peak around 75 msec and a large negative component with a peak around 120 msec (N2). Points A and B were not suitable for recording of the VEPs because some rats showed no N2 peak. The amplitude of peaks N1 to P at point E, upper the left optic layer of the superior colliculus, was higher than those from other points. Point E was the best position for recording of the VEP from dura in Slc: Wistar/ST rats.
Animals↗
[Age-related changes in the visual function of WBN/Kob rats: a behavioral study].
Changes in visual function with increasing age were studied in male WBN/Kob rats, a new diabetic strain. In order to detect visual abnormalities in WBN/Kob rats, 5 WBN/Kob and 5 Wistar/ST (control) rats from each group were examined at 5, 9, 13, 17, 23, 27, 36, 45, 54, 67 and 80 weeks of age using dark and light distinction and open-field tests. The rates at which WBN/Kob rats selected the dark area were 85.0 to 100%, 58.8% and 52.6% at 5 to 54, 67 and 80 weeks of age, respectively, while those for Wistar/ST rats were 85.0 to 100% in each age group. Visual abnormality was obvious in WBN/Kob rats aged 67 and 80 weeks, compared with Wistar/ST rats (P < 0.05). There were no significant signs of visual abnormality in the open-field test. Detection of visual abnormality seems to be possible from 67 weeks of age.
Aging↗
Protection of BALB/c mice against methicillin-resistant Staphylococcus aureus infection by intraperitoneal administration of nucleoside-nucleotide mixture.
The effect of intraperitoneally administered nucleic acid components (nucleoside-nucleotide mixture) on the recovery from methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection was studied in mice. Two experiments were conducted in which BALB/c mice were fed a nucleotide-free 20% casein diet for 30 days. On the 10th day, the mice were inoculated intravenously with viable MRSA organisms. The mice were intraperitoneally administered nucleoside-nucleotide mixture or saline (control) daily from the onset of the experiment (experiment 1) or from the day of inoculation (experiment 2). The survival rate in the nucleoside-nucleotide group in experiment 1 (70%) was significantly higher than that in the saline group (20%) (p < 0.05). In experiment 2, the survival rate in the nucleoside-nucleotide group (55%) tended to be higher than that in the saline group (36%) without statistically significant difference; furthermore, in the surviving mice, the viable MRSA organisms recovered from the spleen and the kidney were fewer in the former group than in the latter group (p < 0.05). The studies showed that the intraperitoneal administration either before or after the MRSA challenge of the nucleoside-nucleotide mixture was effective for the recovery of the mice from the infection.
Animals↗
Ala1048-->Asp mutation in the kinase domain of insulin receptor causes defective kinase activity and insulin resistance.
We identified a heterozygous missense mutation that substituted aspartic acid (GAC) for alanine (GCC) at codon 1048 of the insulin receptor gene in a patient who displayed typical symptoms of Type A syndrome of insulin resistance. The proband's mother and younger brother were also found to be heterozygous for the mutation. We constructed the identified mutant insulin receptor cDNA by site-directed mutagenesis, transfected the mutant cDNA into COS 7 cells, and found that kinase activity of the mutant insulin receptors was markedly impaired. Ala1048 is located in the kinase domain of the insulin receptor beta-subunit and is conserved in most of protein-tyrosine kinases. Besides, neighboring Glu1047 is invariant in all protein kinases and is thought to be involved in interaction with ATP. Photoaffinity labeling of the mutant insulin receptor with ATP analogue, 8-azido (alpha-32P)ATP was not influenced by the mutation, suggesting that the mutation did not inhibit ATP binding but possibly interfered with subsequent phosphoryl transfer. Insulin-stimulated phosphorylation of exogenous substrate by partially purified insulin receptors prepared from COS 7 cells that were cotransfected with wild-type and mutant insulin receptor cDNAs was markedly impaired, whereas autophosphorylation was decreased by approximately 50% of wild-type receptors. These results indicated that the identified heterozygous substitution of Asp for Ala1048 in insulin receptor was responsible for insulin resistance of this patient.
Adolescent↗
Effect of synthetic protease inhibitor on histologic changes and free radical activity in hamsters with pancreatic cancer.
To investigate the effects of synthetic trypsin inhibitors on pancreatic cancer, camostat (FOY-305) was administered orally to hamsters with experimental pancreatic cancer induced by diisopropanol nitrosamine (DIPN). The effect of free radicals on carcinogenesis was examined by measuring the tissue levels of the scavengers superoxide dismutase (SOD) and glutathione peroxidase (GSX-Px), and pancreatic tissues were examined histologically. Cancers developed in all hamsters that survived 24 weeks in the DIPN group and the FOY group, but 80% of the cancers in the DIPN group were tubular adenocarcinomas, and 91% of those in the FOY group papillary adenocarcinomas. The SOD activity in the DIPN group was significantly lower in the cancerous area and the borderline region than in the non-cancerous region and normal tissue. SOD activity in the cancerous and borderline regions was higher in the FOY groups than in the DIPN group. GSH-Px levels in the borderline and non-cancerous regions were significantly higher in the FOY group than in the DIPN group. These results suggest that the synthetic protease inhibitor slows the progress of pancreatic cancer by its free radical scavenging activity.
Adenocarcinoma↗
[Relationship between abdominal fat distribution assessed by computed tomography and serum lipids in the elderly].
A nutritional assessment is necessary to evaluate the pathophysiological state of patients, and serum lipids are one of the factors which must be evaluated. Body fat distribution is considered to be associated with cardiac diseases, metabolic diseases and hypertension. In this study, we performed quantitative measurements of fat distribution by X-ray computed tomography (CT) in 31 elderly outpatients. Thirteen males (mean age 74.8 years) and 18 females (mean age 75.4 years) were examined by abdominal CT. All subjects had body mass indices within the normal range and did not have malignant disease, hyperlipidemia, liver dysfunction or diabetes mellitus. CT scans were carried out at the level of the middle abdomen; these scan slices included intraabdominal fat which consisted of omental, retroperitoneal and perirenal adipose tissues. Subcutaneous fat areas and intraabdominal fat areas were measured from six 10-mm-thick slice films using a 2-dimensional computerized calculator. The relationship between serum lipids and fat distribution was also examined. The ratio of intraabdominal adipose tissue area to subcutaneous adipose tissue area (V/S) was higher in males than in females. V/S correlated positively with serum triacylglycerol and correlated negatively with serum HDL-Ch. These results suggest that the measurement of body fat distribution is important to evaluate lipid metabolism and nutritional states in the elderly.
Adipose Tissue↗
[A case of megaloblastic anemia with abnormally high urine level of beta-aminoisobutyric acid].
A 78-year-old man was admitted to our hospital with anemia and jaundice. Hematological studies revealed hyperchromic macrocytic anemia, and biochemical studies revealed findings of hemolysis. The folic acid level was low and megaloblasts were observed in the bone marrow. From these findings, the patient was diagnosed as having megaloblastic anemia due to folic acid deficiency. This patient had been a heavy alcohol drinker in the habit of drinking alcohol without meals. He began to eat regular meals in the hospital, and the anemia and jaundice improved gradually. Since liver cirrhosis was suspected, amino acid analysis of the urine was performed, and abnormal excretion of beta-amino-isobutyric acid (BAIB) was found. According to the amount of BAIB excreted, the Japanese population can be divided into low and high BAIB excretors comprising 65% and 36%, respectively. BAIB is also considered to reflect dissimilation of thymine. The present patient was included in the high excretion group because of the abnormally high urine level of BAIB, which was considered to be caused by ineffective hematopoiesis in the bone marrow as a result of his megaloblastic anemia. For this reason, dissimilation of thymine was considered to have been active in this patient.
Aged↗