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Biomedical subjects

T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 235 records · Page 13Linked to original sources
PubMed1990

Structural and functional characterization of human aromatase P-450 gene.

The gene encoding aromatase P-450 (CYP XIX) has been isolated from two types of human genomic DNA libraries. It spans at least 70 kb and consists of 10 exons. The translational initiation site and the termination site are located in exon 2 and exon 10, respectively. The promoter region of the gene contains a TATA box, a CAAT box and two putative AP-1 binding sites beginning at -28, -83, -55 and -68 bp, respectively, from the transcriptional initiation site. In addition, a palindromic nucleotide sequence is observed between -209 and -196 and two types of repetitious hexanucleotide (consensus: AATGAA and CCATAAGG) are also present within the regions between -485 and -433 and between -358 and -331. Transient expression studies of chloramphenicol acetyltransferase constructs bearing various lengths of 5'-flanking region of the gene show that the region between -500 and -243 contains negative cis-acting element(s), whereas the region between -242 and -183 is required for efficient transcriptional activity. Northern blot analysis demonstrates that the expression of aromatose P-450 gene is remarkably stimulated by treatment of cells with 12-O-tetradecanoyl-phorbol 13-acetate. By chloramphenicol acetyltransferase assay the region up to nucleotide position -242 relative to the transcriptional initiation site is shown to participate in the transcriptional responsiveness to this phorbol ester.

Amino Acid Sequence↗
PubMed1990

Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta.

A full-length cDNA clone encoding steroid 11 beta-hydroxylase (P-45011 beta) has been isolated from a cDNA library derived from human adrenal tumor. The insert of the clone contains an open reading frame encoding a protein of 503 amino acid residues together with a 4 bp 5'-untranslated region and a 576 bp 3'-untranslated region to which a poly(A) tract is attached. The promoter region of the P-450(11) beta gene has also been isolated from a genomic library derived from human pre-B cells. It contains a TATA box, a putative cAMP-responsive element, several repeated sequences and two sequence elements similar to the consensus sequence for binding of AP-1. A transient expression assay in Y-1 adrenal tumor cells demonstrates that the promoter activity is remarkably enhanced by treatment of the cells with cAMP. In addition, analysis using deletion mutants containing various lengths of the 5'-flanking region of the gene suggests that several cis-acting elements participate in transcriptional regulation of human P-450(11) beta gene.

Adrenal Gland Neoplasms↗
PubMed1990

[Combined postoperative radiotherapy and chemotherapy for malignant gliomas].

A retrospective analysis was performed on 70 patients with malignant supratentrial astrocytic gliomas (astrocytoma Grade III or glioblastoma multiforme) treated with radiotherapy combined with vincristine (VCR), ACNU and PS-K. From January 1979 through December 1983, 27 patients were treated with treatment protocol A (group A). Protocol A was as follows: (1) total dose of 50 to 65 Gy radiation was given after surgery; (2) radiation plus combination VCR (0.02 mg/kg IV on 1st and 29th day of radiation) and ACNU (2 mg/kg IV 24 hrs after VCR) (3) after synchronized radiotherapy, ACNU (2 mg/kg IV every 6 or 8 weeks) and PS-K (3 or 6 g PO every day). Other 43 patients were treated with treatment protocol B (group B) from January 1984 through June 1988. Protocol B was as follows: (1) radiation dose was same as protocol A; (2) radiation plus combination VCR (0.02 mg/kg IV one day before radiotherapy) and ACNU (2 mg/kg IV on 1st and 1 mg/kg IV on 7, 21, 35th day, 1 hour before radiotherapy) (3) maintenance chemotherapy was same as protocol A. The difference between protocol A and protocol B was based on treatment schedule of ACNU. The characteristics of all patients were studied and identified, mainly age, histologic type, initial performance status, extent of tumor resection, maintenance chemotherapy. The reduction rate of tumor volume was 46.7% in the A group and 49.9% in the B group (not significant). The survival rates at 1, 2 and 3 years after surgery were 74.1%, 55.6% and 51.9% respectively for A group, and 80.5%, 42.4%, and 42.4%, respectively for B group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

A three-dimensional method for calculating currents induced in bodies by extremely low-frequency electric fields.

A user-friendly, numerical program has been developed to permit the calculation of induced currents in modeled bodies of human and infrahuman subjects. The program is based on a charge-simulation method (CSM), and it takes into account the three-dimensional (3-D) character of the extremely-low-frequency (ELF) electric field and of the models to be exposed. The principle of the method is to simulate a 3-D object, for example, an animal model, by a combination of several parts (blocks) having simple geometric forms such as a sphere, a cylinder, or a cone. This approach permits easy preparation of input data on the dimensions of the blocks and their positions in a 3-D arrangement. Other input data, such as the coordinates of the contour points and the imaginary values of charges inside objects, which are necessary in the calculations by CSM, are produced automatically by selecting an appropriate "level" for each block, according to its importance. To simulate parts having irregular shapes, special blocks may be added. In one series of experiments, induced currents were calculated for a baboon model in various postures: standing upright, positioned on four legs, and sitting on the floor. Calculated currents, the total induced current in particular, agreed very well with experimental values. Local currents in parts of the baboon models were more variable, ranging from 5% to 17% of measured values in the case of induced currents in the head. Some problems with this method, such as the effect of the dimensions of blocks or the choice of block levels, are discussed.

Animals↗
PubMed1990

Changes in the mode of calcium and phosphate transport during rat incisal enamel formation.

The distribution of 45Ca, 32PO4, 22Na, and calcein in the freeze-dried sections of rat lower incisor was examined. Also, the ratio of 45Ca to 32PO4 transported into the enamel at various developmental stages was studied after the simultaneous injection of 45Ca and 32PO4. The distribution of calcein fluorescence indicated the presence of an extracellular route from capillary to enamel in the areas of both the secretory and smooth-ended ameloblasts. Autoradiograms showed that the 45Ca incorporation into the enamel in the smooth-ended ameloblast region was higher than that into the secretory enamel, and a remarkably high incorporation was observed in the enamel of the apical two-thirds of the ruffle-ended ameloblast region. Although the 32P incorporation into the enamel of the smooth- and ruffle-ended ameloblast region was higher than in the secretory enamel, the differences between these two regions were not so evident as that observed in the case of 45Ca. The high labeling of 45Ca and 22Na was observed in the apical two-thirds of the ruffle-ended ameloblasts. The 45Ca/32PO4 ratio in the secretory enamel was significantly lower than that in the blood, but in the enamel of the smooth-ended ameloblast region the ratio was not significantly lower. Contrarily, the ratio in the enamel of the ruffle-ended ameloblast region was much higher than that in blood. These results indicate that the mode of transport of these ions into enamel is altered in relation to the morphological changes of the ameloblasts.

Amelogenesis↗
PubMed1990

Effects of nitrous oxide on the somatosensory evoked response in cats.

The effect of nitrous oxide on the activity of the somatosensory system was studied in cats with brain electrodes implanted chronically. The electrodes were implanted in the primary somatosensory cortex, cortical somatosensory radiation, medial lemniscus and midbrain reticular formation. Alterations in the excitability of the primary sensory pathway were assessed by the changes of the input to and output from these brain areas: the response in the medial lemniscus to the stimulation of the skin represented the input to the thalamic relay nucleus and the response recorded in the cortical sensory radiation represented the output from the thalamic relay nucleus. The concentrations of nitrous oxide studied were 50% and 75% in oxygen, and the drug effect was concentration-related. The cortical response to peripheral stimulation was suppressed in amplitude by more than 40% of the control with 75% nitrous oxide, and the response in the cortical radiation was suppressed by 20% of the control with the same dose of nitrous oxide. The response in the cortical radiation to stimulation of the medial lemniscus was suppressed by 20% of the control and the postsynaptic component of the cortical response to the stimulation of the medial lemniscus was suppressed by more than 50% of the control. The multi-unit activity of the brainstem reticular formation was enhanced by nitrous oxide in a dose related manner. The excitability of the thalamic relay nucleus and the primary somatosensory cortex was suppressed by natural slow wave sleep when the reticular multi-unit activity was suppressed, and they were enhanced by paradoxical phase of sleep when the reticular multi-unit activity was enhanced. These findings indicated that the degree of suppression of excitability by nitrous oxide is similar in both the thalamic relay nucleus and sensory cortex, and its action on the brain stem reticular formation is different from that on the primary sensory system. The suppression of sensory functions shown in the present study provides a certain clue to the understanding of the neural basis that though nitrous oxide does not produce deep surgical anesthesia, it does induce potent analgesia and sedation during surgery.

Journal Article↗
PubMed1990

Timing of operation for aortic regurgitation: relation to postoperative contractile state.

With angiography and pressure measurement, we determined left ventricular volume, wall stress, and systolic performance in 30 patients with aortic regurgitation before and after successful aortic valve replacement. End-systolic wall stress was greatly elevated preoperatively and decreased to normal postoperatively. Systolic pump performance assessed as ejection phase indexes was severely depressed preoperatively and improved to normal or near-normal postoperatively in most patients. The ratio of end-systolic wall stress to end-systolic volume index (ESS/ESVI), an index of myocardial contractility, was greatly decreased before operation. Postoperatively, the ratio increased in all patients, becoming normal in 12 of the 13 patients who had a preoperative ESS/ESVI of 2.9 or greater. However, 15 of 17 patients in whom the ESS/ESVI ratio was less than 2.9 still had subnormal ratios, which indicates the presence of irreversible contractile dysfunction. Stepwise multivariate analysis showed that preoperative ESS/ESVI was the only independent discriminator of postoperative normalization of the contractile function as assessed by ESS/ESVI. After aortic valve replacement, myocardial contractile state does not return to normal in a considerable number of patients. It is important to offer aortic valve replacement for aortic regurgitation before the chance for a good functional result is lost. The ESS/ESVI ratio may be a useful index in determining the timing of operation in patients with aortic regurgitation.

Adult↗
PubMed1990

Effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic metabolizing enzymes.

Glycol ethers have been extensively used in industry over the past 40-50 years. Numerous studies on the toxicity of glycol ethers have been performed, however, the effects of glycol ethers on the hepatic drug metabolizing enzymes are still unknown. We studied the changes of the putative metabolic enzymes, that is, the hepatic microsomal mixed function oxidase system and cytosolic alcohol dehydrogenase, by the oral administration of diEGME and EGME. Adult male Wistar rats were used. DiEGME was administered orally; 500, 1000, 2000 mg/kg for 1, 2, 5 or 20 days and EGME was 100, 300 mg/kg for 1, 2, 5 or 20 days. Decreases in liver weights were produced by highest doses of diEGME (2000 mg/kg body wt/day for 20 days) and EGME (300 mg/kg body wt/day for 20 days). DiEGME increased hepatic microsomal protein contents and induced cytochrome P-450, but not cytochrome b5 or NADPH-cytochrome c reductase. The activity of cytosolic ADH was not affected by diEGME administration. On the other hand, EGME did not change cytochrome P-450, cytochrome b5 or NADPH-cytochrome c reductase. The activity of cytosolic ADH was increased by repeated EGME treatment. Therefore it is suspected that the enzyme which takes part in the metabolism of diEGME is different from that of EGME, although diEGME is a structural homologue of EGME.

Administration, Oral↗
PubMed1990

Immunohistochemical and ultrastructural localization of epidermal growth factor receptor in human liver and hepatocellular carcinoma tissues.

Expression of epidermal growth factor receptor (EGF-R) in human hepatocellular carcinoma (HCC), hepatoblastoma and non-cancerous liver tissues was investigated immunohistochemically in order to evaluate the possible role of EGF-R expression in neoplastic transformation of hepatocytes. Immunoreactive EGF-R molecules were identified on frozen sections by means of the avidin-biotin immunoperoxidase complex technique using a monoclonal antibody recognizing an epitope of the external domain of human EGF-R. Linear positive staining was present on the surface of carcinoma cells in one hepatoblastoma and in 9 of 11 HCCs. In addition, an enhanced level of surface EGF-R expression was observed on the tumor cells in 9 of 12 cases in comparison with that on hepatocytes in surrounding non-cancerous liver tissue, which in most cases showed chronic inflammation, hepatocyte injury or regeneration. No positive staining in the form of coalescent cytoplasmic granules was present in HCC or hepatoblastoma cells, nor in the cytoplasm of hepatocytes in normal or non-cancerous diseased liver tissue. Little or no reactivity was present on the surface membrane of hepatocytes in the normal liver tissues of 8 control cases. Furthermore, immunoelectron microscopy revealed the localization of this immunoreactive EGF-R molecule on the plasma membrane. Considering that the functional form of EGF-R could be localized on the plasma membrane, the enhanced expression of immunoreactive EGF-R on the tumor cell surface demonstrated here may suggest a possible role of EGF-R in the development or progression of human HCC as well as in hepatocyte regeneration.

Carcinoma, Hepatocellular↗
PubMed1990

Mechanism of diethyldithiocarbamate-induced gastric ulcer formation in the rat.

Diethyldithiocarbamate (DDC) was injected subcutaneously in the rat and the mechanism of gastric ulcer formation was investigated. DDC induced gastric ulcers in a dose-dependent manner. DDC significantly suppressed gastric mucosal copper-zinc superoxide dismutase (Cu, Zn-SOD) activity at 2 hr. However, manganese-superoxide dismutase (Mn-SOD) activity was not changed. Gastric mucosal blood flow (GMBF) decreased to 52% of the control level at 2 hr after administration of DDC and gradually increased to reach the control level by 7 hr. A Shay rat preparation (4 hr) was used to study gastric secretion. DDC (200, 400 and 800 mg/kg) inhibited acid secretion to about 80% of the control level. Histopathological examination of the gastric mucosa after administration of DDC revealed mucosal congestive findings from 1 hr to 3 hr. These data suggested that the mechanism of DDC-induced gastric ulcer formation may be attributable to a decreased level of GMBF and O2- production owing to decreased SOD activity.

Animals↗
PubMed1990

Hepatic neoplasms: detection with hepatoportal subtraction angiography--a new technique of DSA.

A new technique for hepatic intraarterial digital subtraction angiography (DSA)--hepatoportal subtraction angiography (HPSA)--that emphasizes the enhancement of tumors by suppressing liver parenchymal enhancement has been developed. The tumor detection sensitivity of HPSA was evaluated prospectively in comparison with that of conventional hepatic intraarterial DSA, unenhanced computed tomography (CT) or CT enhanced with iodine-containing contrast material (conventional CT), CT with iodized oil, and ultrasound (US). For 84 detected lesions of hepatoma, the sensitivity of HPSA was 92%, statistically superior to the 71% of hepatic intraarterial DSA (P less than .002), the 42% of US (P less than .001), and the 39% of conventional CT (P less than .001) and nearly the same as the 90% of CT with iodized oil. Among 33 lesions of metastasis, HPSA depicted 91%; conventional CT, 93%; US, 87%; and hepatic intraarterial DSA, 76%. HPSA was more sensitive than hepatic intraarterial DSA, but the difference was not statistically significant. Compared with hepatic intraarterial DSA, HPSA enabled detection of more faintly enhanced tumors, and this technique was considered useful for detecting small hypervascular hepatic tumors.

Adult↗
PubMed1990

Left ventricular ejection performance, wall stress, and contractile state in aortic regurgitation before and after aortic valve replacement.

Left ventricular ejection performance, wall stress, and contractile state were evaluated in 35 patients with chronic aortic regurgitation. Cineangiography and pressure measurements were obtained before and a mean of 26 months after aortic valve replacement, and data were compared with those from 30 normal control subjects. The relation between quantitative changes in wall stress and changes in ejection fraction after surgery was determined. Preoperatively, end-systolic stress was elevated in patients with aortic regurgitation (218 +/- 45 vs. 160 +/- 23 kdynes/cm2 [mean +/- SD] for control subjects, p less than 0.01), and ejection fraction was depressed (0.46 +/- 0.11 vs. 0.65 +/- 0.05, p less than 0.01). End-systolic stress decreased postoperatively (151 +/- 41 kdynes/cm2, p less than 0.01) and ejection fraction increased (0.58 +/- 0.11, p less than 0.01). The magnitude of increase in ejection fraction correlated significantly and negatively (r = -0.65) with the quantitative change in end-systolic stress after surgery. Contractile function, as assessed by the ejection phase index-end-systolic stress relation, did not significantly change: 23 of 35 patients preoperatively and 18 of 35 patients postoperatively had values that clearly fell below the 95% confidence limit of the ejection fraction-end-systolic stress relation for controls. After surgery, individual ejection fraction-end-systolic stress relationships demonstrated a shift parallel to the regression curve for the control subjects. Moreover, persistent postoperative left ventricular hypertrophy was significantly associated with persistent contractile dysfunction. Thus, late improvement in left ventricular ejection performance after aortic valve replacement can be attributed to the reduction in end-systolic stress. Contractile function itself was not improved by surgery. Persistent postoperative hypertrophy may be a marker for myocardial contractile dysfunction.

Adolescent↗
PubMed1990

Light microscopic autoradiography for study of early changes in the distribution of water-soluble materials.

An approach using autoradiography for the study of early changes in the distribution of water-soluble materials and the chemography involved was investigated. Radioactive calcium chloride (45Ca) was injected into the iliac vein of a rat. Ten seconds after the injection the rat was frozen in hexane (-90 degrees C). The frozen rat was embedded in 5% sodium carboxymethyl cellulose and blocked in the coolant. A sheet of plastic tape coated with a synthetic rubber glue was fastened to the trimmed block surface, and whole-body sections 2-10 microns thick were cut with a disposable microtome knife. Selected sections were freeze-dried and then covered with a dried autoradiographic emulsion film about 1 microns thick. The autoradiograph clearly showed the distribution of radioactive calcium in the calcification zone of long bones. The samples chosen to assess chemographic artifacts showed positive and negative chemographies on most of the tissues when these were kept at 23 degrees C, and although both chemographic effects were significantly reduced when the samples were kept at -20 degrees C, cells in several tissues still exhibited positive and negative chemographies. The technique can be used for the study of any animal whose size is suitable for whole-body freeze-sectioning.

Animals↗
PubMed1990

Postoperative reversibility of left ventricular hypertrophy and myocardial function in aortic valvular disease.

Pre- and postoperative left ventricular (LV) mass and myocardial contractile state were evaluated in 62 patients with aortic regurgitation (AR) and in 20 patients with aortic stenosis (AS). Preoperatively, there was a significant inverse correlation between LV mass and end-systolic wall stress (ESS)/end-systolic volume index in AR patients and AS patients. In patients with preoperative LV mass exceeding 250 g/m2, ejection fraction failed to return to normal postoperatively, despite reduction in ESS close to the normal controls. Our results indicated that myocardial function was irreversible even in postoperative unloading conditions, when preoperative LV mass exceeded 250 g/m2 in AR patients as well as AS patients.

Aortic Valve↗