Search PubMed⌕ Search

Biomedical subjects

H Sawada

Publications and source records attributed to H Sawada.

At least 217 records · Page 12Linked to original sources
PubMed1995

Descemet's membrane in the iridocorneal-endothelial syndrome: morphology and composition.

The iridocorneal-endothelial syndrome is a disease of the ocular anterior segment characterized by corneal failure, glaucoma and iris destruction. Specular photomicroscopical and histological studies suggest the disorder is caused by a population of abnormal corneal endothelial cells. In other corneal endotheliopathies Descemet's membrane, the basement membrane underlying the endothelial cells, is disfigured by the presence of an abnormal region of extracellular matrix termed a posterior collagenous layer, which is laid down by the diseased endothelial cells. In this study we sought to establish the typical morphology and composition of Descemet's membrane in the iridocorneal-endothelial syndrome. Ultrastructural examination of Descemet's membrane in 27 keratoplasty specimens identified three morphologic patterns. In the majority there was a posterior collagenous layer which in all cases consisted of an anterior layer of wide-spaced collagen and a posterior layer of microfibrils embedded in an amorphous matrix. In four specimens which did not possess a posterior collagenous layer the anterior banded zone of Descemet's membrane was absent. In five corneas Descemet's membrane was normal. The composition of the posterior collagenous layer was examined by immunoelectron microscopy (five corneas) and histochemistry (six corneas). Collagen Types I, III, V, VI and VIII, fibronectin, tenascin and oxytalan were microfibrillar components, collagen Type VIII formed wide-spaced collagen whilst laminin was present in the amorphous matrix. The stereotyped derangements of structure and composition identified in the endothelial basement membrane may significantly influence the pathobiology of this disorder.

Adult↗
PubMed1995

Analysis of the alternative promoters that regulate tissue-specific expression of human aromatic L-amino acid decarboxylase.

Previously we identified two alternative first exons (exon N1 and exon L1) coding for 5' untranslated regions of human aromatic L-amino acid decarboxylase (AADC) and found that their alternative usage produced two types of mRNAs in a tissue-specific manner. To determine the cis-acting element regulating the tissue-specific expression of human AADC, we produced three kinds of transgenic mice harboring 5' flanking regions of the human AADC gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The transgene termed ACA contained -7.0 kb to -30 bp in exon N1, including the entire exon L1; ACN contained -3.6 kb to -30 bp in exon N1; and ACL contained -2.8 kb to -42 bp in exon L1. The ACA transgenic mice expressed CAT at extremely high levels in peripheral nonneuronal tissues, such as pancreas, liver, kidney, small intestine, and colon, that contained endogenous high AADC activity, whereas CAT immunoreactivity was not detected in either catecholaminergic or serotonergic neurons in the CNS. Thus, it was suggested that the ACA transgene contained the major part of cis-regulatory elements for the expression of AADC in peripheral nonneuronal tissues. On the other hand, the ACN transgenic mice moderately expressed CAT in various tissues except for the lung and liver, and the ACL transgenic mice showed moderate CAT expression only in the kidney.

Animals↗
PubMed1995

Alteration of catecholamine phenotype in transgenic mice influences expression of adrenergic receptor subtypes.

Agonist-induced regulation of adrenergic receptors (ARs) has an important role in controlling physiological functions in response to changes in catecholamine stimulation. We previously generated transgenic mice expressing phenylethanolamine N-methyltransferase (PNMT) under the control of a human dopamine beta-hydroxylase gene promoter to switch catecholamine specificity from the norepinephrine phenotype to the epinephrine phenotype. In the present study, we first examined changes in catecholamine metabolism in peripheral tissues innervated by sympathetic neurons of the transgenic mice. In the transgenic target tissues, a high-level expression of PNMT led to a dramatic increase in the epinephrine levels, whereas the norepinephrine levels were decreased to 48.6-87.9% of the nontransgenic control levels. Analysis of plasma catecholamines in adrenalectomized mice showed large amounts of epinephrine derived from sympathetic neurons in the transgenic mice. Subsequently, we performed radioligand binding assays with (-)-[125I]iodocyanopindolol to determine changes in binding sites of beta-AR subtypes. In transgenic mice, the number of beta 2-AR binding sites was 56.4-74.9% of their nontransgenic values in the lung, spleen, submaxillary gland, and kidney, whereas the beta 1-AR binding sites were regulated in a different fashion among these tissues. Moreover, northern blot analysis of total RNA from the lung tissues showed that down-regulation of beta 2 binding sites was accompanied by a significant decrease in steady-state levels of the receptor mRNA. These results strongly suggest that alteration of catecholamine specificity in the transgenic sympathetic neurons leads to regulated expression of the beta-AR subtypes in their target tissues.

Animals↗
PubMed1995

Acquired hypochromic and microcytic sideroblastic anaemia responsive to pyridoxine with low value of free erythrocyte protoporphyrin: a possible subgroup of idiopathic acquired sideroblastic anaemia (IASA).

Patients with idiopathic acquired sideroblastic anaemia (IASA) usually show macrocytic or normocytic anaemia and increased free erythrocyte protoporphyrin (FEP). The mean cell haemoglobin concentration is normal or slightly low. Here we report a pyridoxine-responsive IASA patient with microcytic and hypochromic anaemia and low FEL level; these features are usually seen in cases of hereditary sideroblastic anaemia. Microcytosis increased during therapy. There may be a subgroup of IASA with microcytic and hypochromic anaemia, low normal FEP and some response to pyridoxine like hereditary sideroblastic anaemia.

Adult↗
PubMed1995

PCR detection of Ti and Ri plasmids from phytopathogenic Agrobacterium strains.

A universal primer set (VCF/VCR) for PCR analysis based on the sequences of the virC operon located on Ti and Ri plasmids was designed to detect these plasmids from phytopathogenic Agrobacterium strains. With the VCF (sequence, 5'-ATCATTTGTAGCGACT-3') and VCR (sequence, 5'-AGCTCAAACCTGCTTC-3') primer set, DNA fragments of 730 bp in length were amplified from cell lysates of 10 rhizogenic and 65 tumorigenic agrobacteria. DNA sequencing and Southern hybridization analysis confirmed that the amplified fragments corresponded to the target region. The PCR method is considered convenient for routine determination of the potential pathogenicity of Agrobacterium strains.

Base Sequence↗
PubMed1995

[Effect of newly developed analogue of growth hormone releasing peptide [D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102)] on growth hormone secretion in adult male rats].

The effect of a newly developed hexapeptide; D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102) on GH secretion was studied in adult male rats. KP-102 induced a large plasma GH response at a dose of 0.5 micrograms/kg BW in conscious rats, although GH-releasing abilities of KP-102 varied markedly depending on the phase of GH secretion. Among urethan-anesthetized rats, KP-102 alone exerted a small influence on GH secretion, but it produced a large plasma GH response in the presence of exogenous GH-releasing factor (GRF). The rest of studies were performed on urethan anesthetized rats. During intermittent administration of GRF, the somatotropes became refractory to a large bolus dose of GRF, but KP-102 induced a marked increase of plasma GH. The GH response to KP-102 alone or KP-102 with GRF was significantly augmented when cysteamine HCl was previously administered. Although KP-102 and GRF acted synergistically on GH secretion in control animals, they acted additively in cysteamine-administered rats. Taken together, these findings suggest that the KP-102-induced GH secretion largely depends on GRF and the secretagogue potentiates the GRF effect by antagonizing the SS action at the level of somatotropes. It is concluded that KP-102 alone or in combination with GRF provides a means of stimulating GH secretion in the face of elevated inhibitory tone mediated by SS.

Anesthesia↗
PubMed1995

[A descriptive analysis of cognitive activities involved in locating fishing points: In the case of fishermen of Toyoshima Island, Hiroshima Prefecture].

This study aimed at descriptive understanding of traditional methods involved in locating fishing points and navigating to them in the sea, and investigate associated cognitive activities. Participant observations and interviews were conducted for more than 30 fishermen who employed hand-line or long-line fishing methods near Toyoshima Island, Hiroshima Prefecture. The main findings were: (1) Fishermen readily perceived environmental cues when locating fishing points, which enabled them to navigate to a correct point on the sea. (2) Their memory of fishing points was not verbal, but visual, directly tied to the cue perception, and was constantly renewed during fishing activities. (3) They grasped configurations of various natural conditions (e.g., swiftness of the tide, surface structure of the sea bottom) through tactile information from the fishing line, and comprehended their surroundings with accumulated knowledge and inductive inferences. And (4) their cognitive processes of perception, memory, and understanding were functionally coordinated in the series of fishing work.

Adult↗
PubMed1995

[Effect of a combination treatment using imipenem/cilastatin sodium with G-CSF on infections in neutropenic patients with hematological malignancies].

The clinical effectiveness of a combination treatment using imipenem/cilastatin sodium (IPM/CS) with G-CSF was studied in neutropenic patients (< 500/mm3) with hematological malignancies and secondary infections. Thirty seven patients were entered in the trial, and 30 patients were eligible. This combination was effective in 20 patients, thus the overall efficacy rate was 66.7 percent. The combination was effective in all 6 cases with septicemia, in 10 case out of 15 cases with fever after chemotherapy (efficacy rate; 66.7%), in 3 out of 8 cases with respiratory infections including 7 cases with pneumonia (efficacy rate; 37.5%), and a case with laryngopharyngitis. According to the order of the administration, the efficacy rates were 60.0% in 5 cases in whom G-CSF treatment was started before IPM/CS, 66.7% in 21 cases given both G-CSF and IPM/CS simultaneously, and 75.0% in 4 cases in whom IPM/CS was started before G-CSF. The difference was statistically not significant on the efficacy rates in the three groups. The efficacy in 18 cases treated with monotherapy on antibiotic was 72.2% and that in 12 cases treated with IPM/CS in combination with other antibiotics was 58.3%, and the difference in the efficacy rates in these two groups was not statistically significant. According to the neutrophil counts before and after the treatment, high response rate (60.0%) was obtained in cases of severe neutropenia (less than 100/mm3). Bacteriological examinations showed that all of bacteria detected as pathogens (10 strains of Gram-positive bacteria and 6 strains of Gram-negative bacteria) were eradicated, though 3 strains were replaced by other pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Ischemic hepatitis due to anthracycline-induced cardiac insufficiency in a patient with acute myelocytic leukemia (M0)].

A 25 year-old woman diagnosed as acute myelocytic leukemia (M0) suffered a fourth relapse in February 1992 at which time she already had anthracycline-induced cardiac dysfunction. Although remission was induced by low dose cytosine arabinoside and etoposide combined with pirarubicin, she developed acute heart failure followed by extreme elevation of transaminases level and DIC. Abdominal echography and CT revealed small round lesions in the liver. We diagnosed this episode as ischemic hepatitis because of the following clinical findings; serological markers of virus hepatitis were negative, hypotension and reduced blood flow to the liver were seen, and both transaminases and LDH were markedly elevated. Dobutamin and oxygen inhalation were started, her liver function returned to almost normal levels 8 days later.

Adult↗
PubMed1995

[Progression of senile aortic valve calcification: echocardiographic and clinical assessment].

Factors involved in the progression of senile aortic valve calcification were evaluated by analyzing the clinical and echocardiographic characteristics of patients older than 69 years with senile aortic valve calcification. The patients were divided into three groups; group 1: 46 male and 40 female patients with calcification of one cusp and almost normal pliability of three cusps, group 2: 48 males and 55 female patients with calcification of two or three cusps, mildly reduced pliability of calcified cusps, and aortic valve area (AVA) > or = 2.0 cm2, group 3: 26 male and 31 female patients with calcification of two or three cusps, significantly reduced pliability of calcified cusps, and AVA < or = 1.5 cm2. There were no significant differences in age, weight, height, left ventricular dimension, or left ventricular wall thickness between these three groups. For male patients, the end-diastolic maximum left ventricular outflow tract dimensions (LVOT) in groups 1, 2, and 3 were 20 +/- 2 mm, 19 +/- 2 mm (p < 0.01 vs group 1), and 17 +/- 3 mm (p < 0.001 vs group 1, p < 0.01 vs group 2), respectively. For female patients, the LVOTs of groups 1, 2, and 3 were 18 +/- 2 mm, 16 +/- 2 mm (p < 0.001 vs group 1), and 16 +/- 2 mm (p < 0.001 vs group 1), respectively. Reduction in LVOT was not associated with left ventricular hypertrophy or decrease in dimension of aortic annulus. In female patients, the frequency of mitral annular calcification of group 3 was 61% [p < 0.05 vs group 1 (35%), p < 0.01 vs group 2 (25%)].(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Functional and high level expression of human dopamine beta-hydroxylase in transgenic mice.

Dopamine beta-hydroxylase (DBH; EC 1.14.17.1) catalyzes the production of the neurotransmitter and hormone norepinephrine in the third step of the catecholamine biosynthesis pathway. Transgenic mice were generated with multiple copies of a human DBH minigene construct containing the full-length cDNA connected downstream of the 4-kilobase upstream promoter region to achieve overexpression of DBH. Human DBH mRNA and immunoreactivity were detected tissue-specifically in the brain and adrenal gland of these transgenic mice. The transgene products were correctly processed to a glycosylated mature polypeptide with a molecular mass of 72 kDa and existed in the secretory vesicles as both soluble and membrane-bound forms. We detected a marked increase in DBH activity in various catecholamine-containing tissues of the mice that occurred as a consequence of expression of the catalytically active human DBH enzyme. However, in these transgenics the steady-state levels of norepinephrine and epinephrine were normally maintained without the acceleration of the catecholamine turnover rate, suggesting that there are some regulatory mechanisms to preserve a constant rate of norepinephrine synthesis in spite of the increased amount of DBH protein. These transgenic mice with the minigene construct provide one approach to study the mechanisms underlying biogenesis of the DBH polypeptide and regulation of norepinephrine synthesis.

Adrenal Glands↗
PubMed1994

Peripherally administered (6R)-tetrahydrobiopterin increases in vivo tyrosine hydroxylase activity in the striatum measured by microdialysis both in normal mice and in transgenic mice carrying human tyrosine hydroxylase.

The intraperitoneal administration of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), the natural cofactor of tyrosine hydroxylase (TH), increased the accumulation of L-3,4-dihydroxyphenylalanine (DOPA) measured using microdialysis under the inhibition of aromatic L-amino acid decarboxylase by NSD-1015 (in vivo TH activity) in the striatum both of transgenic mice carrying human TH gene and of non-transgenic mice, to a similar extent by about 4-fold. The results indicate that the peripherally administered 6R-BH4 activates in vivo TH activity in the nigrostriatal dopamine neurons in both non-transgenic and transgenic mice.

Animals↗
PubMed1994

Effect of D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102) on GH secretion in urethan-anesthetized rats.

The effect of a newly developed growth hormone (GH)-releasing hexapeptide (KP-102) on GH secretion was studied in urethan-anesthetized adult male rats. Although KP-102 alone exerted a small influence on GH secretion, it produced a large plasma GH response in the presence of exogenous GH-releasing factor (GRF). During the continuous infusion of GRF, the somatotropes became refractory to a large bolus dose of GRF, but KP-102 induced a marked increase of plasma GH. The GH response to KP-102 alone or KP-102 with GRF was significantly augmented when antiserum to somatostatin (ASS) was previously administered. Although KP-102 and GRF acted synergistically on GH secretion in control animals, they acted additively in ASS-administered rats. The KP-102 effect on plasma GH was significantly attenuated in control animals and ASS-administered rats by prior i.v. injection of antiserum to GRF. Taken together, KP-102 stimulates GH secretion dependent on GRF and appears to act synergistically with GRF by antagonizing the SS effect.

Animals↗
PubMed1994

Production and characterization of monoclonal antibodies specific to multi-ubiquitin chains of polyubiquitinated proteins.

Polyubiquitinated proteins tagged with multi-ubiquitin chains are substrates preferred by the 26 S proteasome (a ubiquitin/ATP-dependent proteolytic complex). Here, we developed a simple method for the efficient preparation of polyubiquitinated proteins which are degraded by the 26 S proteasome in an ATP-dependent manner. Our efficient method enabled us to produce ten monoclonal antibodies that recognized the multi-ubiquitin chains of the polyubiquitinated proteins, but not free ubiquitin or the protein moieties. Eight of the antibodies recognized only the multi-ubiquitin chains of the polyubiquitinated proteins, while the other two antibodies cross-reacted with mono-ubiquitin and methyl-ubiquitin, both of which are linked to proteins via an isopeptide bond, as well as with the multi-ubiquitin chains. Thus these antibodies are novel and useful tools for the identification and quantification of polyubiquitinated proteins in various cells and tissues under physiological and pathological conditions.

Adenosine Triphosphate↗
PubMed1994

Additive effects of cepharanthin in CDDP/hyperthermia combination therapy against transplantable human esophageal cancer in nude mice.

PURPOSE: Additive effects of cepharanthin in CDDP/hyperthermia combination therapy were evaluated. METHODS AND MATERIALS: Nude mice bearing a transplantable human esophageal cancer (ES0-2), classified histologically as a moderately differentiated squamous cell carcinoma, were treated with cepharanthin (20 mg/kg IP) in addition to cis-diamminedichloroplatinum(II) (CDDP; 4 mg/kg IP) and/or hyperthermia at 42 degrees C for 30 min, to determine the additive effects of cepharanthin. Furthermore, effects of cepharanthin on intratumoral concentration of CDDP were evaluated. RESULTS: Cepharanthin itself did not have an anti-tumor effect. This agent did not enhance the anti-tumor effect of CDDP alone, but enhanced the anti-tumor effects of both 42 degrees C hyperthermia alone, and combination therapy with CDDP and 42 degrees C hyperthermia. The concentration of CDDP in the tumors treated by 42 degrees C hyperthermia was slightly higher than in nonheated tumors. Cepharanthin did not affect the intratumoral concentration of CDDP, irrespective of whether hyperthermia was applied. CONCLUSION: Cepharanthin enhanced the effect of CDDP/hyperthermia combination therapy through thermoenhancing effect.

Alkaloids↗
PubMed1994

Nicotine-induced regulation of tyrosine hydroxylase activity in adrenal gland of transgenic mouse carrying human tyrosine hydroxylase gene.

We investigated the effect of subcutaneous injection of nicotine on in vitro tyrosine hydroxylase (TH) activity in adrenal gland and brain of the transgenic mice carrying an 11-kb fragment containing the entire human TH gene. Injection of 5 mg nicotine/kg (as free base) for 3 days caused a statistically significant increase in vitro TH activity in the adrenal gland, whereas brain TH activity was not affected at all. The adrenal gland of non-transgenic C57BL/6J mice treated in the same way as for transgenic mice tended to enhance TH activity, although not to a significant level. This observation might indicate the possibility that the machinery used by nicotine in regulating the properties or expression of TH in the adrenal gland should be similar between transgenic and non-transgenic mice.

Adrenal Glands↗
PubMed1994

Ultrastructural localization of carbonyl reductase in mouse lung.

The immunocytochemical localization of tetrameric carbonyl reductase in the mouse lung was determined by an electron-microscopical immunogold procedure using monospecific antibodies against the enzyme. The labelling of carbonyl reductase was observed within the mitochondria of the ciliated and non-ciliated cells of the bronchioles and the type II alveolar pneumocytes, and the density of labelling in the non-ciliated cells was higher than those in the other cells. No significant labelling was detected over other compartments of the epithelial cells. The labelling was undetectable in the type I alveolar cells, alveolar macrophages and connective tissue cells of the lung. These results clearly indicate the localization of carbonyl reductase to the mitochondrial matrix of these epithelial cells, of which the non-ciliated bronchiolar cells contained particularly high amounts of the enzyme.

Alcohol Oxidoreductases↗