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Biomedical subjects

M Nakazawa

Publications and source records attributed to M Nakazawa.

At least 361 records · Page 20Linked to original sources

Relaxing effects of adenosine in coronary artery in calcium-free medium.

Adenosine relaxes the coronary arteries of various species through A2 receptors. The mechanism(s) by which adenosine causes relaxation of the coronary smooth muscle through changes in intracellular Ca levels is not understood. Therefore, the aim of this study was to evaluate the vasodilatory action of adenosine in normal and in Ca-free medium and the effect of adenosine on 45Ca efflux in Ca-free medium. Prostaglandin F2 alpha (10(-5) M) was used to induce tone in bovine coronary artery rings both in the presence and absence of Ca. Adenosine, 5'-N-ethyl-carboxamide adenosine (NECA) and N6-L-phenyl-isopropyl adenosine (L-PIA) produced concentration-dependent relaxation of the coronary artery rings when precontracted with prostaglandin F2 alpha. Both in normal and Ca-free medium, the order of potency for adenosine analogs (NECA greater than L-PIA greater than adenosine) was similar and 8-phenyltheophylline antagonized the relaxation response to adenosine and its analogs. In Ca-free medium, the concentration-response curves for adenosine and its analogs were shifted to the right, in a parallel fashion, from the curves obtained in Ca-containing solution. Removal of extracellular Ca reduced the maximum responses and slowed the rate of relaxation of adenosine and its analogs and the KB values for 8-phenyltheophylline were significantly increased. In Ca-free medium, adenosine was without an effect on 45Ca efflux in the presence of prostaglandin F2 alpha. The data suggest that the coronary vasodilatory action of adenosine has both extracellular Ca-dependent and -independent components.

Adenosine↗

Hemodynamic effects of acetylcholine in the chick embryo and differences from those in the rat embryo.

It has been reported that acetylcholine induces cardiac anomalies in the chick embryo. Thus, we studied hemodynamic effects of this drug in the chick embryo and also compared them with those in the rat embryo since we found that the effect of caffeine was different between the chick and rat embryos. Acetylcholine was given at doses of 5, 0.5, and 0.05 micrograms into the vitelline vein in chick embryos at Hamburger-Hamilton stage 21 and at a dose of 0.5 micrograms into the placenta in rat embryos at gestational day 12. In the chick embryo, heart rate was reduced to 91, 88, and 87% of control at the end of injection of 0.05, 0.5, and 5 micrograms, respectively, then returned to the baseline level. Vitelline arterial blood pressure was 110% of control with 0.05 micrograms, 134% with 0.5 micrograms, and 142% with 5 micrograms at 1 min after injection. The dorsal aortic blood flow decreased with time after injection, but it was increased only by a 5 micrograms dose at the end of injection. The vascular resistance increased in a dose-dependent manner. In the rat embryo, the change of heart rate was qualitatively similar to that of the chick embryo. The blood pressure did not change significantly. The blood flow velocity at the outflow tract decreased at the end of injection, which indicated the decrease in cardiac output, along with slowing of heart rate, then returned to the control level thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Production of AMP and adenosine in the interstitial fluid compartment of the isolated perfused normoxic guinea pig heart.

The pathway of production of AMP and adenosine in the myocardial interstitial fluid compartment was studied in the isolated perfused normoxic guinea pig heart by collecting the transmyocardial effluent (t.m.e.) with the method of De Deckere and Ten Hoor (1977). Besides adenosine and inosine, AMP was found in t.m.e. Infusion of alpha,beta-methylene adenosine 5'-diphosphate (AOPCP), a specific inhibitor of the ecto 5'-nucleotidase, resulted in increases in t.m.e. AMP and inosine and a decrease in adenosine. Infusion of acetate producing a nearly twofold increase in myocardial AMP content did not increase the t.m.e. AMP even in the presence of AOPCP. In preparations made from 6-OH dopamine treated animals, the t.m.e. adenosine and inosine were reduced and AOPCP produced smaller increases in AMP and inosine, indicating that most if not all of the t.m.e. AMP originated from the sympathetic nerve terminals. Infusions of beta,gamma-imidoadenosine and beta,gamma-methylene adenosine 5'-triphosphate (AMPPNP and AMPPCP), non-hydrolysable analogs of ATP, resulted in dose-dependent increases in the t.m.e. AMP, which were much augmented in the presence of AOPCP. AMPPNP produced similar effects in 6-OH dopamine-treated preparations. As AMPPNP and AMPPCP are good substrates of ATP pyrophosphohydrolase, these findings indicate the presence of ATP pyrophosphohydrolase in the myocardial interstitial space.

5'-Nucleotidase↗

Effect of MCI-176, a new calcium channel blocker, on large and small coronary arteries in dogs.

MCI-176, a new calcium channel blocker, increases coronary blood flow and may improve perfusion in ischaemic areas. Its vasodilating effects on large conductive coronary arteries and the resistive arterioles were therefore compared with those of diltiazem, nifedipine, glyceryl trinitrate and adenosine in anaesthetised open chest beagle dogs. Intracoronary injection of these compounds caused dose dependent increases in coronary flow associated with decreases in the resistance of resistive arterioles, and the rank order of potency was nifedipine greater than adenosine greater than MCI-176 greater than diltiazem greater than glyceryl trinitrate. The resistance of the large conductive vessels was likewise reduced by these agents, except for adenosine. Glyceryl trinitrate showed the highest selectivity to the large conductive vessels, while adenosine showed the lowest and calcium channel blockers were intermediate. Among three calcium channel blockers, MCI-176 had the highest selectivity to the large conductive vessels, while the duration of action was the longest with diltiazem; the duration of action of MCI-176 was intermediate. Thus, MCI-176 is a coronary vasodilator, the potency of which is intermediate between nifedipine and diltiazem, but it has the highest selectivity to the large conductive vessels among these three compounds.

Adenosine↗

Purification and characterization of N-ethylmaleimide reducing enzyme from Candida lipolytica.

N-Ethylmaleimide (NEM) reducing enzyme was purified to homogeneity from cell-free extracts of Candida lipolytica by chromatography techniques. The molecular weight of the native enzyme was estimated to be about 43,000 by gel filtration using Superose 12 and to be 47,000 by SDS-PAGE. This enzyme can use both NADPH and NADH as an electron donor, and catalyzes the reduction of the carbon-carbon double bond of five membered ring compounds which have two conjugated carbonyl groups on both sides of a double bond.

Amino Acids↗

Ganglioside epitope recognized by K99 fimbriae from enterotoxigenic Escherichia coli.

The receptor structure recognized by Escherichia coli possessing K99 fimbriae and by isolated K99 fimbrial fractions was examined by using an equine erythrocyte hemagglutination inhibition test. Both K99-positive organisms (strain B41) and fimbrial preparations reacted with N-glycolylneuraminyl-lactosyl-ceramide (NeuGcLacCer) purified from equine erythrocytes with very high potency. Fimbrial preparations were 253 times more potent than intact organisms, indicating that isolated fimbriae more precisely recognize the structure of NeuGcLacCer than do fimbriae located on the bacterial cell wall. Structurally, the N-glycolyl group of the sialic acid was shown to be essential because substitution of the N-acetyl group for the N-glycolyl group caused the reactivity to completely disappear. The substitution of the O-acetyl group for the C4 hydroxyl group of the sialic acid (4-O-Ac-NeuGcLacCer) also diminished the reactivity by about 500 times, indicating that the fine structure of NeuGc is necessary for recognition. N-Glycolylneuraminyl-neolactotetraosyl-ceramide (NeuGcnLc4Cer) and N-glycolylneuraminyl-neolactohexaosyl-ceramide (NeuGcnLc6Cer), both of which have identical disaccharides at the nonreducing terminal and longer carbohydrate chains, showed reduced reactivity, indicating that the ceramide of NeuGcLacCer is also involved in the recognition. Indeed, NeuGcLac oligosaccharides altered by cleavage of the ceramide or the terminal sialic acid (NeuGc) showed dramatically reduced reactivities. Ten other E. coli strains (isolated from diseased calves) and two strains (isolated from diseased piglets) which possessed the same K99 antigen and various O antigens were used for the recognition test. The results obtained were similar to those mentioned above.

Animals↗

Immunoperoxidase evaluation of pneumonic lesions in calves naturally infected with Pasteurella haemolytica.

Immunoperoxidase technique was applied for pathological study on naturally occurring pneumonic tissues of calves from which Pasteurella haemolytica was isolated. Multifocal necrosis occurred in the lungs of 25 out of 42 calves (59.5%) and P. haemolytica antigen was detected in 22 out of the 25 calves (88.0%). The calves were divided into 3 groups according to the number of P. haemolytica isolated. The positive rate of the bacterial antigen detected by the technique was 66.6% (28/42) on the average, reaching up to 85.7% (18/21) in the group from which the largest number of P. haemolytica was isolated.

Animals↗

[Dysfunction and deficiency of decay-accelerating factor (DAF) demonstrated in the lymphocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH)].

A defective cell-mediated immunity was seen in a 62-year-old female with paroxysmal nocturnal hemoglobinuria (PNH). We studied the functional defect of the patient's lymphocytes and its relation to the deficiency of decay-accelerating factor (DAF) on the lymphocytes. T cells (CD 5+) and B cells (CD 20+) were obtained by cell-sorting using fluorescence-activated cell sorter (FACS-IV). These two types of cells from the patient were demonstrated to be deficient in DAF by the fluorometric measurement of DAF content using monoclonal anti-DAF antibodies. These cells were shown to be more susceptible to complement-mediated lysis than normal human lymphocytes by a complement-mediated lysis study. It was carried out by treatment of the lymphocytes with either anti-CD 5 or anti-CD 20 antibody plus rabbit complement. The lymphocytes became more susceptible to complement-mediated lysis by an additional treatment with an anti-DAF antibody both in PNH and in normal controls. From these results, we suggest that DAF plays an inhibitory role against complement activation on human lymphocytes. The mononuclear cells of the patient responded poorly to phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). Skin tests both for PPD and for DNCB showed negative. From these findings, we suggest T cell function in the patient is impaired. Causative relations of the deficiency of DAF to the poor responses of the lymphocytes to lectins and to negative skin tests were discussed.

CD55 Antigens↗

Intracytoplasmic localization of CD3 antigen in NKH1+ azurophilic granular T-lymphoblastic lymphoma cells.

The intracytoplasmic localization of CD3 antigen was examined in azurophilic granular T-lymphoblastic lymphoma cells obtained from a 27-year-old female. Examination by flow cytometry and an immunohistological method revealed that the surface phenotype of the lymphoma cells were NKH1+, CD5+, CD7+, CD1-, CD2-, CD4-, CD8- and CD16-. CD3 was not detected on the cell-surface by flow cytometry but was found in the cytoplasm using the immunohistological method. CD3 was detected in the perinuclear space and rough endoplasmic reticulum (rough ER) by an immunoelectron microscopic study. An electron microscopic observation of the granules revealed lysosomal structures with low electron density. The lymphoma cells proliferated when cultured in the presence of interleukin-2 but showed no NK (K562) activity before and after culture. The molecular size of metabolically labeled intracytoplasmic CD3 precipitated by Leu 4 monoclonal antibody was identical to that of normal CD3. These results indicate that the lymphoma cells are neoplastic counterparts of immature thymocyte at a very early stage of differentiation and may be related to the lineage of CD3+ NKH1+ T-lymphocyte.

Adult↗

[Hodgkin's disease diagnosed from the numerous Reed-Sternberg cells in the bone marrow].

A 46-year-old female was admitted to our hospital for fever and weight loss in September, 1986. Physical examinations were unremarkable. CBC revealed moderate anemia and leukopenia with abnormal lymphocytes. Examination of the bone marrow (BM) disclosed peroxidase negative blasts and multinucleated or multilobulated giant cells positive for CD30 (Ki-1) antigen. Chest X-ray was negative. CT scan and echography of the abdomen showed minimal enlargement of retroperitoneal lymph nodes (LN). Lymphangiography revealed mild enlargement of the LN without filling defects. Gallium scan was negative. Hence a diagnosis of Hodgkin's disease (HD) stage IVB was made. She was treated with MOPP therapy with modification and obtained a complete remission. BM involvement of HD occurs mostly in advanced stages. We assumed that this is a rare case of HD in which bone marrow metastasis occurred in a very early stage of the disease or that of bone marrow primary.

Antigens, Differentiation↗

Partial agonist activity of celiprolol as assessed in conscious unrestrained dogs in comparison with those of pindolol and labetalol.

The effects of celiprolol on the heart rate (HR) and the total peripheral resistance (TPR) were studied in chronically instrumented conscious dogs in comparison with those of pindolol, propranolol and labetalol. Intravenous injection of pindolol, celiprolol and labetalol increased the HR and decreased the TPR dose-dependently, whereas propranolol did not. The ratios of doses that elicited 12% changes in both parameters (HR12/TPR12) were 4.85 +/- 2.63, 0.61 +/- 0.03 and 0.42 +/- 0.11 for celiprolol, pindolol and labetalol, respectively, indicating the preferential reduction of TPR by celiprolol. Changes in HR and TPR produced by these three agents were antagonized by propranolol dose-dependently. However, inhibition by 3 mg/kg of propranolol was incomplete in the cases of labetalol-induced decrease in the TPR at the dose of TPR12 (51%) and celiprolol-induced increase in the HR at the dose of HR12 (89%). These results suggest that changes produced by celiprolol as well as pindolol and labetalol were mostly explainable by partial agonist activity via beta-adrenoceptors. However, the contribution of the alpha-blocking activity must also be taken into consideration in the case of the reduction of the TPR by labetalol. In addition, there is a possibility that celiprolol may increase HR via its direct action.

Adrenergic alpha-Agonists↗

[Non-Hodgkin lymphoma associated with a long history of protein losing enteropathy].

A 32-year-old man with an 18-year history of protein losing enteropathy (PLE) was admitted to hospital for abdominal distention. On physical examination, he had massive pleural effusion, ascites and edema of the right leg, but no superficial lymphadenopathy or organomegaly. Laboratory studies revealed mild microcytic anemia and hypoproteinemia. alpha 1-antitrypsin clearance was elevated (316 ml/day). Examination of ascites disclosed numerous lymphoblastoid cells of B cell phenotype with mu chain and lambda light chain of immunoglobulin (Ig) in the cytoplasm. Southern blot analysis showed monoclonal rearrangement of mu chain and lambda chain genes. No evidence of lymphomatous involvement of lymph nodes and non-lymphoid organs was found by CT scan, ultrasound echography and gallium scan of the chest and abdomen. Bone marrow biopsy was negative. Thus, a diagnosis of non-Hodgkin lymphoma (NHL) stage IVB limited in the pleural and peritoneal cavities was made. He was treated with the combination chemotherapy of BACOD with high dose ara-C or methotrexate followed by 4 doses of autologous LAK cell infusion resulting in no significant response. The massive pleural effusion, ascites and edema of the leg have not been improved. We consider this to be a rare case of NHL associated with PLE which is extremely resistant to chemotherapy or LAK therapy.

Adult↗

[Conservative management of breast cancer].

Numerous reports have been published concerning conservative treatment of breast cancer in western countries. The survival rates of the treatment are similar to those for radical surgery, but the functional and cosmetic results are much better in the conservative treatment than in radical surgery. Thirty years ago, our hospital encountered 69 cases of conservative treatment for breast cancer. Satisfactory results were obtained. Ten-year survival rates for stage I and II were 76% and 65%, respectively. Recent methods of surgery and radiotherapy for conservative treatment of breast cancer are discussed.

Breast Neoplasms↗

[New selection criterion for Fontan procedure: pulmonary artery clamping test and pulmonary vascular resistance in increased pulmonary blood flow].

A new selection criterion for Fontan procedure, pulmonary artery clamping test (PACT) was developed and employed in 13 candidates for Fontan procedure. PACT was aimed to evaluate the response of pulmonary vascular bed to increased pulmonary blood flow and calculate the pulmonary vascular resistance in the increased pulmonary blood flow as a selection criterion for Fontan procedure, preoperatively. After a median sternotomy incision, an electromagnetic flow meter was employed for measuring the pulmonary blood flow (Qp) on the pulmonary trunk. By clamping the left pulmonary artery and the right pulmonary artery, right pulmonary vascular resistance and the left pulmonary resistance in the pulmonary blood flow of Qp were calculated respectively. By means of electrical analogue, right and left lungs were simulated as resistors in parallel. And the equivalent pulmonary vascular resistance Rpc was calculated as the predicted pulmonary vascular resistance in the increased pulmonary blood flow of two times Qp. Fontan procedure was performed in 9 cases with a Rpc of less than 3 unit.m2 with a successful result and no death. Postoperative cardiac index ranged from 2.6 to 3.7 L/min.m2 with a mean of 2.8 L/min.m2. Postoperative pulmonary vascular resistance ranged from 1.6 to 3.2 unit.m2. Postoperative cardiac index was correlated with postoperative pulmonary vascular resistance. And postoperative pulmonary vascular resistance was well correlated with equivalent pulmonary vascular resistance but was not correlated with preoperative pulmonary vascular resistance measured by Fick's method at the preoperative catheterization. In Fontan procedure, the pulmonary blood flow frequently increases to a certain degree postoperatively. And pulmonary vascular resistance is not a static resistance, but a dynamic resistance. Hence, in discussing a pulmonary vascular resistance as a selection criterion for Fontan procedure, the pulmonary blood flow in which the pulmonary vascular resistance stand should be taken into account. Equivalent pulmonary vascular resistance Qpc is a theoretical selection criterion for Fontan procedure and well reflects the postoperative pulmonary vascular resistance. Fontan procedure can be successfully performed with a Rpc of less than 3 unit.m2.

Adolescent↗

[Megakaryoblastic crisis of chronic myelogenous leukemia cytological and clinical studies in three cases].

Diagnostic significance of the megakaryocyte markers and clinical findings were evaluated in three cases with chronic myelogenous leukemia in megakaryoblastic crisis. Platelet peroxidase (PPO), glycoprotein IIb/IIIa, Ib, von Willebrand factor antigen (vWF: Ag) and demarcation membrane system (DMS) were examined as the megakaryocyte markers. Blast phenotypes were as follows: PPO- IIb/IIIa+ vWF: Ag+ DMS+ in Case 1, PPO+ IIb/IIIa +/- Ib- vWF: Ag +/- in Case 2 and PPO+ IIb/IIIa+ vWF: Ag +/- DMS +/- in Case 3 (-: 0% +/-: less than 10% +: greater than or equal to 10%). In Cases 1 and 3, no markers other than those for the megakaryocyte lineage were detected, but myeloperoxidase-positive blasts coexisted with PPO-positive megakaryoblasts in Case 2. Megakaryoblast phenotypes and involvement of other lineages were much different in each case. Therefore, marker study for cytological diagnosis should be performed in consideration of lineage heterogeneity. As to the clinical findings, no clear features common to the three cases were present. However, multiple osteolytic lesions were demonstrated on bone survey in Case 1 and considered to be caused by the proliferation of megakaryoblasts.

Adolescent↗

Oxymetholone therapy in patients with familial antithrombin III deficiency.

Three patients with familial antithrombin III (ATIII) deficiency, who also have histories of thromboembolism, were treated with oxymetholone in combination with warfarin. Thrombolysis was observed in one patient with acute thrombosis of inferior vena cava during the oxymetholone and warfarin therapy. No further thromboembolic episodes occurred in these patients after initiation of warfarin with or without oxymetholone. The levels of plasma ATIII, alpha 1-antitrypsin, plasminogen and Cl-inactivator were significantly increased in all patients after the introduction of oxymetholone therapy. This suggests that oxymetholone augments anticoagulant and fibinolytic activity. Hence we consider that oxymetholone in combination with warfarin may be possible thrombolytic therapy in patients with familial ATIII deficiency.

Adolescent↗

Structure of the gene encoding the beta-subunit of chicken prolyl 4-hydroxylase.

Prolyl 4-hydroxylase (EC 1.14.11.2) converts peptidyl proline to peptidyl hydroxyproline in procollagen polypeptides during collagen biosynthesis. The active enzyme is a tetramer which is composed of two pairs of non-identical subunits in a molecular form of alpha 2 beta 2. In addition to the tetrameric prolyl 4-hydroxylase (alpha 2 beta 2), the free beta-subunit is also found inside cells. Recently it was shown that the beta-subunit of prolyl 4-hydroxylase is identical to the protein disulfide isomerase and cellular thyroid hormone-binding protein. We previously isolated and characterized cDNAs of the beta-subunit of chicken prolyl 4-hydroxylase. The cDNA of beta-subunit was used to screen a chicken genomic DNA library constructed with the lambda EMBL-3 vector. Two clones, lambda gCPH beta-22 and beta-50, were isolated and characterized by restriction enzyme analysis, heteroduplex analysis, and nucleotide sequencing. The results showed that the 2.5-kb mRNA of the beta-subunit is divided into eleven exons and that the gene is 9.0 kb long. The gene contains consensus sequence for TATA at -24 bp and four CAAT at -57, -157, -194 and -223 bp in the 5' end flanking sequence of the transcription start point. In addition, there are three GC boxes upstream from the TATA box and four GC boxes in the first intron. This is similar to the structure of the alpha 1(I) collagen coding gene (COL1A1). These elements may interact with nuclear factors and play important roles in expression regulation of the beta-subunit gene as has been described in COL1A1.

Amino Acid Sequence↗