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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 541 records · Page 30Linked to original sources
PubMed1992

High myocardial accumulation of radioiodinated digoxin derivative: a possible Na,K-ATPase imaging agent.

In view of the high binding ability of cardiac glycosides to the myocardial Na,K-ATPase, radioiodinated digoxin derivatives were surveyed as candidates for myocardial imaging, with particular emphasis on the noninvasive monitoring of cardiac glycoside therapy. Among the radioiodinated digoxin derivatives surveyed, 125I-digoxin-iodohistamine(bis(O-carboxymethyloxime)) showed the highest accumulation in the myocardium and similar binding ability to Na,K-ATPase as digoxin itself against ouabain displacement, as indicated by in vivo and in vitro studies. Based on these results, 123I labeling of digoxin-histamine(bis(O-carboxymethyloxime)) and imaging in a dog demonstrated uptake in the myocardium.

Animals↗
PubMed1992

Behaviour of tissue plasminogen activator, plasminogen activator inhibitor 1 and their complex in various disease states.

Plasma levels of tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen and t-PA/PAI-1 complex were measured in plasmas from 18 healthy subjects and 75 patients with various diseases (28 patients with haematological malignancies, 20 with thrombotic diseases, five with infectious diseases, four with liver diseases, ten with bleeding disorders and eight miscellaneous conditions). In addition, we studied ten patients with bleeding disorders after DDAVP infusion and 18 healthy subjects after venous occlusion. Plasma levels of t-PA antigen, PAI-1 antigen and t-PA/PAI-1 complex were increased in the patients compared with the healthy subjects. t-PA/PAI-1 complex levels correlated well with t-PA antigen levels and molar concentrations of t-PA antigen were similar to those of the t-PA/PAI-1 complex. Venous occlusion induced an increase in both t-PA antigen and PAI-1 antigen and the molar concentration of the t-PA/PAI-1 complex was equivalent to that of t-PA antigen. Following DDAVP infusion, the levels of t-PA antigen and t-PA/PAI-1 complex increased but PAI-1 antigen levels decreased, and the increase of t-PA antigen was greater than that of t-PA/PAI-1 complex. These findings indicate that PAI-1 antigen exceeds t-PA antigen in healthy subjects and in patients with various diseases. We conclude that part of the t-PA/PAI-1 complex is rapidly cleared from the circulation and that free t-PA increases after DDAVP infusion.

Adult↗
PubMed1992

[Clinicopathological review of Japanese cases with neoplastic angioendotheliosis].

The patient was a 76-year-old female who had been referred to our hospital because of fever of unknown origin on October 15, 1987. On admission, the body temperature was 38.6 degrees C and atonic palsy of the left upper limb was noted. Abnormal laboratory findings included CRP5+, an increase in LDH, Hb 7.9 g/dl. The cause of the fever could not be identified. The fever did not respond to various treatment. The patient developed DIC in late October and died on November 5. In autopsy histological examination revealed tumor cells in the vessels of the generalized organs. A diagnosis of neoplastic angioendotheliosis (NAE) and immunohistologically B lymphoma was made. We reviewed the literature on 37 Japanese cases of NAE. The cases, consisting of 19 males and 18 females, were aged 37-87 years with a median value of 60 years. The symptoms observed during the course were most frequently mental or neurological symptoms and fever, and rash was uncommon. Laboratory findings were non-specific and biopsy was needed for definitive diagnosis. By autopsy, lesions were noted more frequently in the brain, kidneys, and lungs, and the findings in the skin were indeterminate. These observations suggest that when NAE should be considered, kidney, lung or skin biopsy should be performed for definitive diagnosis.

Aged↗
PubMed1992

Amino acid sequences of ferredoxins from Alocasia macrorrhiza Schott in Papua New Guinea.

The amino acid sequences of ferredoxin isoproteins (Fd A and Fd B) from Alocasia macrorrhiza Schott in Papua New Guinea were determined. They consisted of single polypeptide chains of 97 and 98 residues, respectively, and both Fds had a molecular mass of 10,800 Da. There was an 88% identity between the sequences of the isoproteins (Fd A and Fd B). These sequences were compared with those of the closely related plant Fds and their phylogenetic relationships are discussed.

Amino Acid Sequence↗
PubMed1992

[Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibody CEA 102: whole IgG versus F(ab')2 fragments].

In order to improve cancer imaging with radiolabeled antibodies, three factors appeared to be of particular importance: (1) The selection of the most favorable monoclonal antibody directed to tumor-associated antigen. (2) The use of F(ab')2 or Fab fragments. (3) Selection of the most convenient isotope. Monoclonal antibody CEA 102 was produced by immunization by purified CEA, and its F(ab')2 fragments were compared with whole IgG as a radiotracer for radioimmunodetection of the colorectal cancer. Fragments were eliminated from the circulation twice as fast as whole IgG, and tumor-to-background ratio was achieved more than 1 at 2-3 days with F(ab')2, but 6-7 days with whole IgG in tumor bearing nude mice. In clinical study, F(ab')2 demonstrated clear image on the 1 at day after injection, whereas achievement of the image was possible on the 3rd day in whole IgG. These results indicated that fragments are preferred over whole IgG. Therefore fragments make it possible to preclude dual isotope subtraction methods, and omit the long delays before imaging. They also make it possible to use short half life radionuclides with excellent photon properties, such as 123I and 99mTc.

Animals↗
PubMed1992

[The relationship between ploidy and morphological classification of human megakaryocytes].

The relation between polyploidy and morphological classification of human megakaryocytes was studied in bone marrow aspirates from five normal individuals. On a Wright-Giemsa stained smear, megakaryocytes were morphologically classified into four groups according to a modification of Feinendegen's classification which is considered to reflect megakaryocyte maturation. The DNA of the morphologically classified cell is measured by microcytofluorometry using DAPI (4',6-diamidino-2-phenylindole) staining after removing the Wright-Giemsa stain. Most of the normal megakaryocytes were classified into type III (mature megakaryocytes) and the maximum peak in population of the megakaryocyte ploidy was observed at 16N. In each individual, the ploidy showed a similar pattern regardless of the classification. These findings suggest that the development of ploidy depends on a factor different from the one that determined the megakaryocyte maturation of cytoplasm and the ploidy is determined at the level of a megakaryocyte precursor or the most juvenile megakaryocyte.

Adolescent↗
PubMed1992

[Reconstructive surgery for mitral regurgitation caused by degenerative disease--indications for expansion and early clinical outcomes].

Between January 1983 and June 1990, there were 48 patients who underwent surgery for mitral regurgitation due to degenerative diseases. Among these, 20 patients received mitral valve repair. Overall operative mortality was 5% for patients who underwent valve repair, and 7.1% for those who underwent valve replacement. We standardized a maneuver for valve repair in August 1988 in an attempt to expand its indications. There were 35 patients who underwent surgery prior to that date (group 1), and 13 patients after that date (group 2). There were nine patients (25.7%) in group 1 and 2 patients (84.6%) in group 2 who underwent valve repair. Among these, one patient (11%) in group 1 died within 30 days after the operation, but there were no surgical deaths for any patients in group 2. In addition, one patient (11%) in group 1 and one (9%) in group 2 required another operation for valve replacement. Doppler echocardiographic studies performed postoperatively in 18 patients who had undergone valve repair showed that 13 (72.2%) had no regurgitation, 4 (22.2%) had trivial regurgitation, and 1 (5.6%) had mild regurgitation. Postoperative valve area as determined by continuous-wave Doppler echocardiography was 3.7 +/- 1.1 cm2 (mean +/- SD) for patients who had undergone reconstruction and 3.1 +/- 0.7 cm2 for those who had undergone replacement.

Adolescent↗
PubMed1992

[The inhibitory effect of cholecystokinin on phosphatidylcholine synthesis in isolated rat pancreatic acini (II)].

To better understand the mechanism underlying the inhibition induced by cholecystokinin (CCK) of phosphatidylcholine (PC) synthesis, the effects of CCK treatment on the activities of enzyme involved in PC synthesis via CDP-choline pathway were studied in isolated rat pancreatic acini. CCK treatment of acini reduced CTP: phosphocholine cytidylyltransferase activity in both cytosolic and particulate fraction. However, CCK treatment of acini did not alter the activities of choline kinase and phosphocholinetransferase in acini. When acini were labeled with [3H] myristic acid and chased, CCK8 (1 nM) reduced the synthesis of [3H] myristic acid labeled-PC to 27% of control after 60 min-chase period. This inhibition of PC synthesis induced by CCK was accompanied by a delayed disappearance of [3H] diacylglycerol (DAG), the radioactivity of which was 225% of control at 60 min. CCK also induced an increase in [3H] triacylglycerol and [3H] phosphatidic acid in acini. These results suggest that CCK inhibits PC synthesis by inducing the inhibition of CTP: phosphocholine cytidylyltransferase activity. The inhibition by CCK of PC synthesis may contribute to the sustained accumulation of DAG in pancreatic acinar cells.

Animals↗
PubMed1992

[Analysis of pancreatic stone protein gene of hereditary pancreatitis].

To investigate the pathogenesis of hereditary pancreatitis we determined whether pancreatic stone protein (PSP) gene was structurally altered in two independent families diagnosed as hereditary pancreatitis. Because, it has been shown that a decrease in the activity of PSP which inhibits CaCO3 crystal formation in pancreatic juice is closely related to the development of chronic calcifying pancreatitis. Southern blot analysis revealed neither a rearrangement nor a gross deletion of PSP gene in genomic DNA of affected members of both families. Furthermore, six exons of PSP gene amplified by polymerase chain reaction from genomic DNA was directly sequenced, while no apparent base mutation was observed. The immunohistochemical study utilizing monoclonal antibody to PSP showed the presence of immunoreactive PSP in the section of pancreatic tissue obtained from a patient affected with hereditary pancreatitis. However, the level of immunoreactive PSP in the remaining acinar cells of the patient pancreas was not reduced when compared with that of normal pancreas. Results, therefore, indicate that genetic alteration of PSP gene may not be responsible for the pathogenesis of hereditary pancreatitis.

Adolescent↗
PubMed1992

[Natural interferon-alpha induced cytogenetic complete remission in a patient with chronic myelocytic leukemia, diagnosed in early chronic phase with basophilia and normal blood cell counts].

A 57-year-old woman visited to our hospital complaining of paresthesia in the right leg. She had no abnormal physical findings. However, the peripheral blood examination demonstrated 7% basophilia with 8000/microliters WBC count and decreased neutrophil alkaline phosphatase activity (score 37, rate 19%). She was diagnosed as Ph1 chromosome positive CML in early phase by the chromosomal analysis of bone marrow cells. She received subcutaneous injection of natural interferon-alpha at a dosage of 600 x 10(4) IU daily from March 10, 1987. The dosage and administration interval were gradually reduced and prolonged. Since November 1988, weekly injections of 300 x 10(4) IU has been administered as maintenance therapy. Cytogenetic improvement was seen at 4 months after the start of IFN. Disappearance of Ph1 chromosome positive cells was observed on December 11, 1987. It was suggested that the administration of IFN from the early chronic phase played an important role in the control of the disease.

Basophils↗
PubMed1992

[Comparative study of UFT plus mitomycin C and UFT plus doxorubicin in adenocarcinoma. Hirosaki Cooperative Group of Cancer Chemotherapy].

A multicenter cooperative study was conducted to compare the clinical efficacy of UFT-M (UFT, Mitomycin C (MMC)) and UFT-D (UFT, Doxorubicin (DXR)). A total of 62 cases with adenocarcinoma were enrolled in this study. Eligible cases included 25 patients with gastric cancer, 22 with pancreas or biliary tract cancer and 10 with other cancers. They were divided into two groups; 30 in UFT-M and 27 in UFT-D. The treatment schedules were as follows: UFT 400-600 mg/day orally every day, MMC 4-6 mg/m2, IV, every week (UFT-M); UFT 400-600 mg/day orally every day, DXR 20 mg/m2, IV, every 3 weeks (UFT-D). For gastric cancer, 3 of 17 cases treated by UFT-M showed PR, whereas no case showed PR in UFT-D. As for toxicity, bone marrow suppression was more commonly observed in UFT-M than in UFT-D. There was no statistical difference in survival between the two treatment regimens. These results suggested that UFT-D was not effective but UFT-M was a more promising combination therapy against advanced gastric cancer.

Adenocarcinoma↗
PubMed1991

Cholecystokinin inhibits phosphatidylcholine synthesis via a Ca(2+)-calmodulin-dependent pathway in isolated rat pancreatic acini. A possible mechanism for diacylglycerol accumulation.

The effects of cholecystokinin (CCK) and other pancreatic secretagogues on phosphatidylcholine (PC) synthesis were studied in isolated rat pancreatic acini. When acini were incubated with [3H]choline in the presence of 1 nM CCK-octapeptide (CCK8) for 60 min, the incorporations of [3H]choline into both water-soluble choline metabolites and PC in acini were reduced by CCK8 to 74 and 41% of control, respectively. Pulse-chase study revealed that CCK8 reduced both the disappearance of phosphocholine and the synthesis of PC. Other Ca(2+)-mobilizing secretagogues such as carbamylcholine, bombesin, and Ca2+ ionophore A23187 also reduced PC synthesis to the same extent as did CCK8. When combined with 1 nM CCK8, A23187 or carbamylcholine did not further inhibit PC synthesis. Furthermore, W-7 or W-5, a calmodulin antagonist, reversed the inhibition by CCK8 of PC synthesis, suggesting that a Ca(2+)-calmodulin-dependent pathway may be involved in CCK-induced inhibition of PC synthesis in acini. By contrast, neither cAMP-dependent secretagogues such as secretin and dibutyryl cAMP nor a phorbol ester had any effect on PC synthesis in acini. Staurosporine or H-7, a protein kinase C inhibitor, did not affect the inhibition by CCK of PC synthesis. The analysis of enzyme activity involved in PC synthesis via CDP-choline pathway showed that CCK treatment of acini reduced CTP:phosphocholine cytidylyltransferase activity in both cytosolic and particulate fraction, a finding consistent with the delayed disappearance of phosphocholine induced by CCK in pulse-chase study. By contrast, CCK treatment of acini did not alter the activities of choline kinase and phosphocholine transferase in acini. The extent of inhibition by CCK of cytidylyltransferase activity became much larger when subcellular fractions of acini were prepared in the presence of phosphatase inhibitors. In addition, W-7 reversed the inhibitory effect of CCK treatment on cytidylyltransferase activity in acini. When acini were labeled with [3H]myristic acid and chased, CCK8 (1 nM) reduced the synthesis of [3H]myristic acid-labeled PC to 27% of control after a 60-min chase period. This inhibition of PC synthesis induced by CCK was accompanied by a delayed disappearance of [3H]diacylglycerol, the radioactivity of which was 225% of control at 60 min. These results indicate that CCK inhibits PC synthesis by inducing both the reduction of choline uptake into acini and the inhibition of CTP:phosphocholine cytidylyltransferase activity. Furthermore, the results suggest the possibility that the activation of Ca(2+)-calmodulin-dependent kinase in response to CCK may phosphorylate cytidylyltransferase thereby decreasing this enzyme activity in pancreatic acinar cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkaloids↗
PubMed1991

Evident diversity of codon usage patterns of human genes with respect to chromosome banding patterns and chromosome numbers; relation between nucleotide sequence data and cytogenetic data.

The sequences of the human genome compiled in DNA databases are now about 10 megabase pairs (Mb), and thus the size of the sequences is several times the average size of chromosome bands at high resolution. By surveying this large quantity of data, it may be possible to clarify the global characteristics of the human genome, that is, correlation of gene sequence data (kb-level) to cytogenetic data (Mb-level). By extensively searching the GenBank database, we calculated codon usages in about 2000 human sequences. The highest G + C percentage at the third codon position was 97%, and that of about 250 sequences was 80% or more. The lowest G + C% was 27%, and that in about 150 sequences was 40% or less. A major portion of the GC-rich genes was found to be on special subsets of R-bands (T-bands and/or terminal R-bands). AT-rich genes, however, were mainly on G-bands or non-T-type internal R-bands. Average G + C% at the third position for individual chromosomes differed among chromosomes, and were related to T-band density, quinacrine dullness, and mitotic chiasmata density in the respective chromosomes.

Base Composition↗
PubMed1991

Effect of diabetes on photochemically induced thrombosis in femoral artery and platelet aggregation in rats.

Effect of diabetes on thrombogenesis was examined by using a thrombus model with photochemical reaction in the rat femoral artery. In streptozotocin-induced diabetic rats for 8 weeks, the formation of thrombus following endothelial injury was significantly slower than that in non-diabetic rats. Insulin treatment normalized the abnormality of thrombogenesis. Aggregation in washed platelets from rats with diabetes was enhanced. However, platelet aggregation in whole blood was reduced in diabetic rats, and plasma from diabetic rats attenuated platelet aggregation. These results suggest that plasma factor(s) and/or other blood cells modify the hyperaggregability of platelets per se in vivo in diabetic rats. Treatment with insulin improved the aggregation in whole blood and washed platelets. In conclusion, diabetes induces the prolongation of thrombogenesis in the rat femoral artery. Hypoaggregability of whole blood is likely to be partly involved in the abnormal thrombogenesis.

Animals↗
PubMed1991

Cadmium directly acts on endothelin receptor and inhibits endothelin binding activity.

The binding of endothelin (ET) to human placenta ET receptor was strongly inhibited by cadmium ions (Cd2+) (IC50 = 2 x 10(-5) M). Experiments with affinity cross-linking showed that the major 40 kDa receptor was inhibited to form a [125I]ET-1/receptor complex. The mode of inhibition was noncompetitive with respect to ET-1. The inhibitory effect of Cd2+ on solubilized ET receptor was partially reversed by the chelating agent, ethylenediaminetetraacetic acid (EDTA), whereas the effect was irreversible for the membrane-associated receptor. The rat aorta contractions by ET were prevented by pretreatment or addition of Cd2+.

Animals↗
PubMed1991

Primary structure of the virus activating protease from chick embryo. Its identity with the blood clotting factor Xa.

Host cell proteases activating para- and orthomyxovirus fusion glycoprotein precursors play a crucial role in determining the viral tropism in infected organisms. We previously isolated such an endoprotease from the allantoic fluid of chick embryo and showed its close similarity to the activated form of blood clotting factor X (FXa) by partial amino acid sequencing. In this report, we have cloned and sequenced a cDNA of the protease, and show that it is encoded in a single gene as a preproform with all the functional and structural domains known to be characteristic of bovine or human FX, establishing the identity between the protease and FXa.

Allantois↗