Plasma levels of endothelin-1 and thrombin-antithrombin III complex in patients undergoing open chest operations.
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Biomedical subjects
Publications and source records attributed to T Miyauchi.
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Pulmonary artery pseudoaneurysm after PA banding is a rare complication and its mortality is very high. The authors successfully operated on this sort of lesion. To our knowledge, this is the first successful case in Japanese literature. The second of twins was found to be suffering asplenia, dextro cardia, TAPVC, atrioventricular septal defect, corrected TGA and PDA. On the 19th day of life, increasingly pulmonary congestion forced us to operate. We performed PDA ligation, correction of TAPVC, together with extrathoracically adjustable PA banding. 5 months following this operation, spike fever and swelling of anterior thorax were noted. PA angiography was performed, and it showed that the pulmonary artery had been cut through by the band and a pseudoaneurysm had developed. The PA banding was removed and an end-to-end anastomosis of the PA was performed using cardiopulmonary bypass and deep hypothermia with surface cooling. The diameter of the PA anastomosis was designed to be one half that of her aorta. Staphylococcus aureus was cultured from the specimen of the PA band. It was thought to have contributed to the development of this aneurysm. The post operative course was uneventful.
From January to December 1990, we performed a prospective survey of adverse reactions to contrast media at two different institutes of Juntendo University. We collected a total of 4555 case sheets during the period. The radiological procedures we investigated were computed tomography, intravenous urography, arteriography, venography and myelography. Low osmolar iodine contrast medium was used almost exclusively (except for five cases). The overall incidence of adverse reactions was 7.0%, and there were no severe or fatal reactions. The incidence of adverse reactions was higher in females (8.5%) than in males (6.1%). The incidence of adverse reactions increased according to the dose of contrast medium, especially when more than 101 ml was injected. Intra-arterial injection caused adverse reactions most often, followed by regular intravenous injections, followed by bolus intravenous injections. Adverse reactions occurred most often during injection. The next occurred in 5 minutes after injection, and then, 5-10 minutes after the injection of contrast medium. The incidence of adverse reactions was higher in patients with a history of allergy or previous reactions. Allergic adverse reactions were observed at a higher frequency. Pretesting was performed in 56.7% of the cases.
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The efficacy of lymphoscintigraphy and ultrasonography was evaluated in the detection of internal mammary lymph node (IMN) metastases in patients with breast cancer. On histological examination of IMN, 10 patients had metastases (positive group) and 47 did not (negative group). On lymphoscintigraphy, lack of uptake in the parasternal region of the affected side was classified as abnormal. The frequency of this abnormal finding was not significantly different between both groups. On sonography, the thickness of the sonolucent internal mammary area was measured. The thickness of the affected side was 6 mm or more in two patients of the positive group and only one of the negative group. A thickness of over 6 mm on the affected side was statistically significant (p less than 0.05). The difference in thickness between the affected side and the healthy side was 3 mm or more in four patients of the positive group, and was less than 3 mm in all patients of the negative group. A difference in thickness of more than 3 mm between the two sides was extremely significant (p less than 0.001). In conclusion, sonography is valuable in detecting IMN metastases, while lymphoscintigraphy is not useful. Sonography is recommended as an efficient diagnostic modality for IMN metastases.
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An intravital fluorescence microscope system was used to investigate the pharmacological effects of endothelin-1 (ET-1) on the coronary microcirculation in the isolated beating hearts of rats. The heart was perfused by retrograde aortic steady flow with an oxygenated Krebs-Ringer solution containing FITC-dextran. Changes in diameters of coronary microvessels accompanying the cumulative injection of ET-1 in the perfusate were observed and recorded with a video camera system. Coronary perfusion pressure was also measured during each experiment. Bolus injections of ET-1 (1-300 pmole) elicited a dose-dependent increase in perfusion pressure from 54 +/- 6 mm Hg (mean +/- SEM; n = 10, before the ET-1 injection) to 144 +/- 9 mm Hg (n = 8, at the ET-1 dose of 300 pmole). A dose-dependent narrowing of microvessels was also observed. This vasoconstriction was especially prominent in small-sized arterioles; the maximum vasoconstriction of the smaller arterioles was significantly higher than that of the larger arterioles (P less than 0.05). The response induced by ET-1 dose of 3-10 pmole was significantly larger in arterioles than in postcapillary venules in the diameter range between 10 and 40 microns. The vasoconstriction produced by ET-1 was inhomogeneous. Some part of bifurcations of arterioles showed a prominent localized vasoconstriction, and occasionally showed a complete luminal obstruction. Such a segmental vasospasm might be attributed to localized sensitivities of arterioles to ET-1. These findings suggest that ET-1 may have an important role in governing the coronary resistance and regulating the capillary flow in the myocardium.
MK (midkine) and HB-GAM (heparin-binding growth-associated molecule) constitute a new family of heparin-binding growth differentiation factors. The modes of expression of MK and HB-GAM during mouse development were quantitatively examined by mRNA hybridization. The following three distinct patterns of expression were observed in the brain/head region. On the 11th-13th days of gestation, MK was intensely, but HB-GAM relatively weakly expressed; on the 15th-19th days, both MK and HB-GAM expression became weaker; and in the neonatal period, HB-GAM was intensely expressed and MK expression increased slightly. The level of HB-GAM expression was lower than that of MK in the whole embryo on the 11th to 13th days of gestation. HB-GAM mRNA was detected in the kidney of newborn and young mice, where MK was more highly expressed. The identity of the weakly expressed MK and HB-GAM signals was confirmed by means of the polymerase chain reaction in the neonatal brain (MK), the head of 13-day embryos (HB-GAM), and the kidney of 7-day-old mice (HB-GAM). In conclusion, MK and HB-GAM are frequently co-expressed in the same cells and anatomic regions of the fetus or new born mouse, while their modes of expression differ.
The peanut agglutinin (PNA)-binding site is protein-bound Gal beta 1-->3GalNAc, and is a tumor-associated carbohydrate marker expressed in many human carcinomas. PNA-binding glycoproteins isolated from KATO-III human gastric carcinoma cells were deglycosylated by trifluoromethanesulfonic acid, and rabbit antibodies against the core proteins were used to screen a lambda gt11 expression library constructed from these cells. Two different core proteins were identified by this approach. One was polymorphic epithelial mucin (PEM), initially found in breast carcinomas. PEM mRNA was expressed in normal tissues of the stomach, colon, and lung, but not in the small intestine, thyroid, and spleen. High levels of PEM mRNA were detected in some nude mouse-transplanted carcinomas, i.e. colorectal, pancreatic, stomach, and lung carcinomas. The other core protein was a novel one called MGC-24, which has a molecular mass of 24 kDa, is rich in hydroxyl amino acids and cysteine, and lacks repeating motifs. The mature MGC-24 glycoprotein behaved as a high-molecular-mass one upon SDS-polyacrylamide gel electrophoresis even after neuraminidase treatment. Treatment with endo-alpha-N-acetylgalactosaminidase in the absence of neuraminidase significantly changed the staining pattern by anti-MGC-24, confirming that MGC-24 carried PNA-binding sites. MGC-24 mRNA was intensely expressed in normal tissues of the colon, small intestine and thyroid, and in some nude mouse-transplanted colorectal and pancreatic adenocarcinomas.
Four tyrosine-protein kinases that reacted with antibodies specific to p62c-yes, p60c-src, p60c-src+, and p59fyn, respectively, were solubilized from a rat brain particulate fraction and separated by casein-Toyopearl column chromatography. Possible p59fyn, with a pI of 6.5, was purified 490-fold as a single 59-kDa protein band on SDS-PAGE. The purified enzyme contained almost no phosphotyrosine residues but was autophosphorylated with Mg2+. ATP exclusively at tyrosine residues, with a concomitant increase in the kinase activity toward tyrosine-glutamate (1:4) copolymers. The rate of the copolymer phosphorylation was proportional to the square of the enzyme concentration, suggesting activation through intermolecular catalysis. In the presence of Mn2+, however, the reaction showed a first-order dependence on the enzyme concentration.
In search of factors mitigating the final outcome of ischemic and epileptic brain damage, we tested a novel dibenzoxazepine derivative (BY-1949), as the compound has been shown to be effective under these two conditions. First, using rat brain, we assessed whether or not BY-1949 affects the Na+,K(+)-ATPase activity. Although in vitro applications of either BY-1949 or its three major metabolites did not cause any apparent effects, both acute and chronic oral administrations of the compound (10 mg/kg) invariably increased the Na+,K(+)-ATPase activity in the synaptosomal plasma membranes by increasing Vmax values. Second, it was shown by this study that the drug treatment caused marked increases in the uptake of both glutamic acid and gamma-aminobutyric acid into the synaptosomes. These results suggest that the activity against ischemic/epileptic brain damage by BY-1949 is explicable, at least partly, in terms of improvement of ionic derangements across the neural membranes via Na+,K(+)-ATPase activation.
We examined the effects of endothelin-1 (ET-1) on pulmonary hemodynamic and transvascular fluid filtration and the conversion of big endothelin-1 (big ET-1), a precursor of ET-1, in isolated perfused rabbit lungs at constant vascular and airway pressures. Furthermore we examined whether ET-1 contributes to cyclooxygenase metabolism. The perfusate flow decreased significantly after bolus administration of 1 or 0.1 nmol of ET-1. Lung weight did not increase throughout the experimental period. Big ET-1- (1 nmol) induced decrease in the flow was slow in developing, although the maximum response was comparable to that induced by the same dose of ET-1. The concentration of bit ET-1 in the perfusate progressively decreased, while that of ET-1 increased in a time-dependent manner. Phosphoramidon, an inhibitor of metalloproteinase, suppressed the pressor effect of big ET-1 (P less than 0.01) and the increase in the concentration of ET-1 in the perfusate (P less than 0.05). The present findings provide the first evidence suggesting that the potent vasocontractile effect of big ET-1 in pulmonary circulation can be attributed to the production of ET-1 by the conversion from big ET-1 in the vascular bed. ET-1-induced perfusate flow changes were not affected by indomethacin, and the concentration of 6-ketoprostaglandin F1 alpha, a metabolite of prostacyclin, did not increase after ET-1 administration.
The minimum region in salmon calcitonin (sCT) which induces antigenicity and gastrointestinal disturbances has been identified by examining the cross-reactivity of several sCT fragments and CT analogs with antisera from sCT-treated patients, and by examining inhibition of gastrointestinal motility of these sCT fragments and CT analogs in conscious dogs. Sixteen residues at the N-terminus of sCT comprised the minimum fragment capable of inducing both activities. Human CT (hCT) showed no antigenicity and a four-order weaker inhibition of gastrointestinal motility than sCT. Based on these data, we synthesized the human and salmon chimeric CT, ACT-15, in which the 16 N-terminal residues were those of hCT and the 16 C-terminal residues were those of sCT. ACT-15 had no cross-reactivity with the antisera and had almost the same weak gastrointestinal inhibition effect as hCT in dog and rat models. Nevertheless, it retained a hypocalcemic activity and an analgesic activity comparable to sCT. These results suggest that the amino acid residues in the N-terminal half of CT are responsible for the formation of antibodies and the induction of gastrointestinal disturbances, but may not influence calcium metabolism or analgesia. Clinical studies of ACT-15 will be needed to confirm this hypothesis.
We investigated changes in serum lipoprotein(a) (Lp(a)) and C4b-binding protein (C4bp) levels following acute myocardial infarction (AMI). Serum lipids, apolipoproteins, C-reactive protein (CRP), sialic acid and haptoglobin (Hp) were also measured and evaluated. The study involved 16 patients (11 men, 5 women, mean age 68.2 +/- 8.4 years) with AMI admitted within 12 h after the onset of illness. CRP rose sharply and immediately after the onset of AMI, reaching its maximum level on the 3rd day of illness. This was followed by temporary increases in sialic acid and Hp, both of which peaked on the 7th day of illness. The Apo A-I level was significantly lower on the 14th day, while the Apo B level was significantly lower on the 3rd day. Serum total cholesterol (T-Ch), HDL-Ch and LDL-Ch showed temporary decreases after the onset of illness. Serial examination of the serum of patients with AMI yielded the following findings; 1) Both Lp(a) and C4bp levels rose temporarily with similar patterns of variation, and 2) they took longer time to peak (around the 14th day) and lasted longer than the increases in the other acute reactive proteins.
We examined serum lipids, lipoproteins, apolipoproteins (Apo), lipoprotein(a) (Lp(a)), C4b-binding protein (C4bp) and lathosterol in 22 normolipidemic (serum total cholesterol less than 220 mg/dl and serum triglycerides less than 150 mg/dl) male patients with coronary artery disease (CAD) and 33 normal male subjects. Many of the patients in the CAD group with normal total cholesterol (T-Ch) and triglycerides (TG) had higher TG, low-density lipoprotein (LDL)-Ch, beta-lipoprotein (Lipo) and Apo B values and lower high-density lipoprotein (HDL)-Ch, Apo A-I and Apo A-II values than those of the control group. Differences were also observed in the beta-Lipo/HDL-Ch, Apo B/Apo A-I, and HDL-Ch ratios and the atherogenic index [A.I. = (T-Ch--HDL-Ch)/HDL-Ch], all of which are generally accepted as indices for atherosclerosis. Even in CAD patients with normolipidemia, the HDL-Ch/T-Ch ratio and A.I. seemed to be important risk factors. In addition, Lp(a) and lathosterol, an accepted indicator of whole-body cholesterol synthesis, were higher in the CAD group. The CAD group also appeared to have a higher C4bp value, suggesting that this parameter is correlated with other lipids.
Epithelioid cells that had grown in short-term cultures derived from 10 cases of adenocarcinoma (PCa) and 10 cases of hyperplasia (BPH) of the prostate were karyotyped by the G-banding method for the pathogenesis of these disease. PCa specimens included 4 well, 2 moderately, and 4 poorly differentiated types, and were obtained by perineal needle biopsy from 4 patients in stage B and 6 patients in stage D2. Cells liberated from metastatic lymph node lesions of 2 patients with poorly differentiated PCa were also analyzed directly without cultivation in vitro. All BPH specimens were obtained by prostatectomy, and cells that had grown in epithelioid pattern in short-term cultures were analyzed. In PCa, hyperploidy was seen in all but 2 cases. Structure analysis disclosed abnormality of chromosome 16 in 4 PCa, deletion of Y in 3 PCa, abnormality of chromosomes 7, 14, 15, 18, and 19 in 2 PCa, and abnormality of chromosomes 3, 4, 17, and 21 in 1 PCa. Multiple markers were observed in 1 patient, and hyperploidy in another patient with metastatic lymph nodes. All but 2 cases of BPH were diploid. Normal male karyotypes were seen in 6 BPH. Trisomy of chromosomes 7 and 16 were observed in 2 BPH. Of 4 patients with stage B PCa, 3 who have been alive for 3 years to date had multiple abnormalities, whereas 1 patient who died 2 years after diagnosis had few abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)