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Biomedical subjects

C Suzuki

Publications and source records attributed to C Suzuki.

At least 91 records · Page 5Linked to original sources

Identification of regions in the human angiotensin II receptor type 1 responsible for Gi and Gq coupling by mutagenesis study.

Previous mutagenesis studies of angiotensin II (Ang II) receptor type 1 (AT1) have focused on determining the regions responsible for Gq coupling using the rat AT1 receptor. We created human AT1 receptor mutants, expressed them in COS-7 cells, and identified the domains crucial for Gi coupling as well as for Gq coupling. Substitution of Asp125, Arg126, Tyr127, and Met134 by Gly, Gly, Ala, and Ala in the highly conserved sequence of the second intracellular loop in most G protein-coupled receptors provided a mutant AT1 receptor which lost the ability to couple to both Gq and Gi with no impairment in its binding to Ang II. A truncated mutant lacking the carboxyl terminal 50 residues was completely deficient in coupling to Gi, whereas it retained full ability to bind to Gq, in contrast to the rat AT1 receptor. These findings demonstrate that the cytoplasmic tail in the human AT1 receptor is the determinant of specific Gi coupling.

1-Methyl-3-isobutylxanthine↗

Fumonisin B1 toxicity in male Sprague-Dawley rats.

Male rats were gavaged with fumonisin B1 (FB1) once daily for 11 consecutive days at doses of 0, 1, 5, 15, 35, and 75 mg FB1/kg body weight. Urine osmolality (at 5-75 mg FB1/kg) and organic ion transport in kidney slices (at 5-75 mg FB1/kg) were reduced. Urinary excretion of protein (at 15-75 mg FB1/kg) and of the enzymes LDH (at 5-75 mg FB1/kg), NAG (at 5-75 mg FB1/kg) and GGT (at 15-75 mg FB1/kg) were increased. These findings were indicative of glomerular and tubular toxicity. Histopathologic changes in the kidney consisted of necrosis of tubular epithelia of variable extent accentuated in the inner cortex. These changes were present at 1 and 5 mg FB1/kg and were more pronounced at 15-75 mg FB1/kg. Serum enzymes indicative of hepatotoxicity (ALT, GGT) were elevated compared to controls at 75 mg FB1/kg only. There were noticeable increases in mitotic figures in hepatocytes at 35-75 mg FB1/kg, while single cell necroses were increasingly numerous from 15-75 mg FB1/kg. The kidneys were considered to be the primary target organs in this study.

Acetylglucosaminidase↗

[Serum concentration of pyridinoline cross-linked carboxy-terminal telopeptide of type-I collagen (ICTP) and carboxyterminal propeptide of human type I procollagen (PICP) in the diagnosis of bone metastases].

Recently discovered bone metabolic markers are expected to play an additional role in the diagnosis of bone metastasis. We measured bone metabolic markers, serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of human type I procollagen (PICP) in 224 patients with breast cancer (106 with bone metastases), 61 patients with prostatic cancer (30 with bone metastases), 45 patients with lung cancer (17 with bone metastases) and 13 patients with miscellaneous cancers (7 with bone metastasis) and compared the values in the presence and absence of bone metastasis. ICTP and PICP increased significantly in patients with bone metastases. By the analysis of sensitivity and specificity, the cut-off levels were considered to be 5.0 ng/ml for ICTP and 140 ng/ml for PICP. In lung cancer (bone metastases are mostly of osteolytic), ICTP was excellent marker in detecting bone metastasis. In breast cancer (bone metastases are mostly of mixed type), ICTP was good in detecting bone metastases. In prostatic cancer (bone metastases are mostly of osteoblastic), ICTP and PICP were good markers in detecting high grade of bone metastases. Over all, ICTP was more sensitive in the diagnosis of bone metastases than PICP. However, both markers were not effective in detecting low grade bone metastases. ICTP and PICP should play a supportive role to imaging modalities in the diagnosis of bone metastases.

Aged↗

[Suitable measure for medicines resulting from pharmacist-visit and assistance for a good treatment].

Our medication team, consists doctors, nurses, pharmacists, and other staffs, made an effort to satisfy our patients with medical treatment. We especially tried to guarantee patient rights. Pharmacists visited patients in September 1995, seeking to inform every patient about effects and side effects of medicines using the "Medicine Information Sheet" with samples. As a result, in one case now under treatment by medicine, he no longer needs it. Then, our medication team had a conference and his doctor changed his prescription. In another case, we found a symptom suspected to be a side effect of a medicine. We asked his doctor about it, and he stopped the medicine in question. His medical condition then became better. This resulted in a "suitable amount" of medicine. We are confident that this is also necessary for every patient under treatment at home, when a pharmacist visits his or her home and informs them about the effects and side effects of medicines, and assists them to assure good treatment.

Aged↗

A synergistic increase in transplantable peripheral blood stem cells in mice by co-administration of recombinant human interleukin 6 and recombinant human granulocyte colony-stimulating factor.

We examined the effects of co-administration of recombinant human (rh) IL-6 (10 micrograms/day) and rh granulocyte colony-stimulating factor (G-CSF) (0.35 micrograms/day) on the number of peripheral blood cells and peripheral progenitor cells in mice. Among blood cells counts, only white blood cells were synergistically enhanced by co-administration of rhIL-6 and rhG-CSF. Moreover, it was found that co-administration of rhIL-6 and rhG-CSF also caused a marked synergistic increase in the number of peripheral blood progenitor cells. Namely, in combination with rhG-CSF, which alone induced a 170-fold increase in peripheral granulocyte-macrophage colony-forming units (CFU-GM) on day 14, rhIL-6 synergistically increased the number of CFU-GM to more than 1600-fold higher than the number in control mice. Administration of rhIL-6 alone induced a 46-fold increase in CFU-GM. Similar synergistic increases of other hematopoietic progenitors, such as colony-forming units in spleen and megakaryocyte colony-forming units in blood, were also observed in mice co-administered rhIL-6 and rhG-CSF. The survival rate of lethally irradiated recipient mice transplanted with mononuclear cells from 100 microliters of blood from mice administered rhIL-6 and/or rhG-CSF was examined. When mononuclear cells from mice co-administered rhIL-6 and rhG-CSF were injected, survival rate at day 100 was 92%. In contrast, recipient mice transplanted with mononuclear cells from mice administered either rhIL-6 or rhG-CSF alone showed a survival rate of 31% or 46%, respectively, although transplantation of mononuclear cells from control mice failed to rescue any lethally irradiated recipient mice. These results suggest that co-administration of rhIL-6 and rhG-CSF may be useful for peripheral blood stem cell transplantation.

Animals↗

Toxicity of fumonisin B1 administered intraperitoneally to male Sprague-Dawley rats.

The toxicity of purified fumonisin B1 (FB1) administered ip was examined in male Sprague-Dawley rats. FB1 was injected at 7.5 or 10 mg/kg body weight/day for 4 consecutive days. This resulted in significant reductions in body weight, food consumption and faeces production. Polyuria without a compensatory increase in water consumption was observed in treated rats. Erythrocytosis, elevated haematocrits and haemoglobin levels were attributed to dehydration. Nephrotoxicity in treated rats was evident by clinical changes including elevated blood urea nitrogen and by subtle changes in kidney morphology. Histopathology and serum biochemistry also indicated that the liver was an important target organ in FB1-treated rats. A small increase in liver glutathione concentration was also evident in rats receiving 10 mg FB1/kg body weight. Effects on the immune system included reduced thymus weight, disseminated thymic necrosis and consistently elevated serum immunoglobulin M levels. Circulating phagocytic cell numbers were elevated in treated rats, probably owning to tissue damage associated with ip dosing. The liver and kidneys appear to be target organs of FB1 in Sprague-Dawley rats.

Animals↗

The primary and subunit structure of a novel type killer toxin produced by a halotolerant yeast, Pichia farinosa.

A halotolerant yeast, Pichia farinosa KK1 strain, produces a unique killer toxin termed SMK toxin (salt-mediated killer toxin) which shows its maximum killer activity in the presence of 2 M NaCl. The toxin consists of two distinct subunits, alpha and beta, which are tightly linked without a disulfide bond under acidic conditions, even in the presence of 6 M urea. Under neutral conditions, however, the alpha subunit precipitates, resulting in the dissociation of the subunits and the loss of killer activity. The nucleotide sequence of the SMK1 gene predicts a 222 amino acid preprotoxin with a typical signal sequence, the hydrophobic alpha, an interstitial gamma polypeptide with a putative glycosylation site, and the hydrophilic beta. Amino acid sequence analyses of peptide fragments including the carboxyl-terminal peptides fragments including the carboxyl-terminal peptides from each subunit suggest that the alpha and beta subunits consist of amino acid residues 19-81 and 146-222 of the preprotoxin, respectively, and the molecular weight of the mature alpha beta dimer is 14,214. The KEX2-like endopeptidase and KEX1-like carboxypeptidase may be involved in the stepwise processing of the SMK preprotoxin. The maturation process and the functions of the SMK toxin are compared with the K1 toxin of Saccharomyces cerevisiae.

Amino Acid Sequence↗

Effect of recombinant human erythropoietin administration on peripheral blood neutrophil counts of premature infants.

To clarify whether administration of recombinant human erythropoietin (rHuEpo) may have toxic effects on neutrophil production in premature infants, 10 low birth weight infants who received rHuEpo, 200 U/kg per week, were studied retrospectively. Treated infants were compared with 10 untreated infants. None of the infants studied had infection antenatally or postnatally. In both groups the neutrophil count remained greater than 5000/mm3 for the first 3 weeks and decreased markedly at approximately 4 weeks. Although reticulocyte counts were significantly elevated in the rHuEpo-treated group, the difference in neutrophil counts between the groups was not significant. In addition, administration of rHuEpo did not exert any significant effect on granulocyte-macrophage colony formation of circulating hematopoietic progenitors in neonates. Thus no evidence was found that administration of rHuEpo has toxic effects on granulopoiesis in premature infants.

Erythropoietin↗

Antitumor polysaccharides from a Chinese mushroom, "yuhuangmo," the fruiting body of Pleurotus citrinopileatus.

A water-soluble polysaccharide, FI, and water-insoluble polysaccharides, FII and FIII were extracted from Pleurotus citrinopileatus mushrooms. After fractionation, the antitumor activity of the fractions against Sarcoma 180 implanted in mice were examined, and the following active polysaccharides were obtained: Water-soluble polysaccharides FIo: A heteropolysaccharide containing 9.8% protein, and composed of glucose, mannose, arabinose, and galactose. FA-2-b-beta: A glycoprotein consisting of glycan:protein = 40:60 w/w, with the glyco-chain composed of glucose, xylose, mannose, galactose, and fucose. FA-3: A glycoprotein consisting of glycan:protein = 50:50 w/w, and glycan moiety consisting of glucose, galactose, xylose, mannose, and fucose. Water-insoluble polysaccharides. FIII-1: Protein-containing beta-D-glucans, FIII-1-a, and -b were obtained from FIII-1 by gel filtration, composed of glucan:protein = 80:20, and 68:32 w/w, respectively. The glucan moieties of both were almost all (1-->3)-beta-D-glucan, and their molecular weights were 68 x 10(4) and 40 x 10(4). FIII-2: Protein-containing beta-D-glucans, FIII-2-a, and -b, were obtained from FIII-2 by gel filtration, with molecular weights 190 x 10(4) and 120 x 10(4), respectively. Both were almost all composed of glucan:protein = 87:13 w/w. Both glucan moieties were mainly (1-->3)-beta-D-glucan.

Amino Acids↗

Antitumor protein-containing polysaccharides from a Chinese mushroom Fengweigu or Houbitake, Pleurotus sajor-caju (Fr.) Sings.

Protein-containing polysaccharides extracted from fruiting bodies of a Chinese fungus named Feng Wei Gu, were fractionated and purified, and their antitumor activities were tested, out of which the following active fractions were obtained. FIo-a: A protein-containing xyloglucan, MW 280,000, polysaccharide: protein = 76:24 (w/w), polysaccharide consisting of Man:Gal:Xyl:Glc = 2:12:42:42 (molar ratio). [alpha]D23 + 25.3 degrees. FA-2: A protein-containing mannogalactan, MW 120,000, polysaccharide: protein = 76:16 (w/w), consisting of Xyl:Man:Gal = 9:35:56 (molar ratio), [alpha]D23 + 98.5 degrees. FII-1: A Protein-containing xylan (62:21 w/w). MW 200,000, [alpha]D23 + 8.7 degrees. FIII-1a: A protein-containing glucoxylan (15:71 w/w), [alpha]D23 + 30.7 degrees, MW 90,000, consisting of Glc:Xyl = 40:44 (molar ratio). FIII-2a: A protein-containing xyloglucan, MW 70,000, polysaccharide:protein = 69:3 (w/w), polysaccharide consisting of Xyl:Glc = 36:62 (molar ratio). [alpha]D23 + 38.6 degrees.

Animals↗

[Evaluation of newborns with brain disease using 123I-IMP SPECT].

Eleven newborns with suspected cerebral disease were evaluated using 123I-IMP SPECT. In a normal subject, high uptake was shown in the sensorimotor cortex, thalamus, midbrain-brainstem, and cerebellar vermis. Decreased perfusion was also noted in the frontal lobe. In hypoxic ischemic encephalopathy (HIE), diffuse decreased uptake which showed no redistribution in the white matter was seen in two patients. These two patients had a poor prognosis. In one of the other 4 patients with HIE, persistent defect in parasagittal area was recognized and the patient also had a poor prognosis. In one of two patients with tuberous sclerosis, 123I-IMP SPECT showed high uptake in the area of increased density shown in CT. Thus, 123I-IMP SPECT of newborn has characteristic findings different from the adult. This tracer also might have a prognostic value of clinical improvement following HIE.

Amphetamines↗

Ten-year complete remission in an 84 year-old patient with acute myeloid leukemia.

We report an unusual case in which complete remission of acute myeloid leukemia (AML) had lasted for almost 10 years in a patient who was 94 years and 7 months old as of September 1989. An 84 year-old man was admitted to our hospital with gingival bleeding on October 15, 1979. Hematological data were: RBC 327 x 10(4) microliters, hemoglobin concentration 10 g/dl, platelets 3.8 x 10(4) microliters and WBC 9000 microliters, including 34% blastic cells. Bone marrow aspiration showed nucleated cells 48.0 x 10(4)/microliters with 69.2% blastic cells. He was diagnosed as having AML (M2). Induction chemotherapy consisted of daunorubicin, cyclocytidine, an anhydride analogue of cytosine arabinoside, and prednisolone (DCP). Complete remission was achieved after 1 month of this therapy. After two cycles of consolidation therapy (DCP), intensification therapy (DCP) was performed twice. Thereafter, complete remission lasted without any further therapy, up to September 1989, when he died of pancreatic cancer. The prolonged disease-free survival in this extremely aged patient was attributed to the high sensitivity of leukemic cells to DCP therapy and his good performance status at the time of initial induction chemotherapy. This is the oldest patient with long-term remission, lasting for over 5 years, to be reported in Japan. If an elderly patient with typical acute leukemia has a good performance status, intensive chemotherapy should be tried at least once, while carefully controlling complications specific to the elderly.

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