Calcium binding to abnormal fibrinogens with a single amino acid replacement in the NH2-terminal region of fibrin alpha- or beta-chain.
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Binding Sites↗
Biomedical subjects
S Asakura
Publications and source records attributed to S Asakura.
Characterization of an abnormal fibrinogen Osaka V with the replacement of gamma-arginine 375 by glycine. The lack of high affinity calcium binding to D-domains and the lack of protective effect of calcium on fibrinolysis.
Prolonged thrombin time was completely corrected by the addition of millimolar concentrations of calcium in a new abnormal fibrinogen, Osaka V. Analysis of lysyl endopeptidase digests of A alpha-, B beta-, or gamma-chains by high performance liquid chromatography, and the following amino acid sequence analysis of relevant peptides revealed that about 50% of the gamma-chain has a replacement of gamma-arginine 375 by glycine. When fibrinogen was digested with plasmin in the presence of millimolar concentration of calcium, the amount of fragment D1 was about 50% of the normal control, and the rest was further cleaved to fragment D2, D3, or D62 with an apparent Mr of 62,000. Plasmic digestion of cross-linked fibrin in the presence of calcium resulted in the appearance of an abnormal fragment with an apparent Mr of 123,000 as well as fragments D2, D3, and D62, concomitant with the decrease of D dimer. The gamma-remnant of the abnormal fragment proved to be a cross-linked complex of the normal D1 gamma-remnant and residues 374-406/411 of the abnormal gamma-chain. The number of high affinity Ca(2+)-binding sites for the normal fibrinogen and fibrinogen Osaka V obtained by equilibrium dialysis was 2.88 (about 3) and 1.85, respectively, and that for the abnormal molecules was calculated as 0.9 (about 1) from their relative amounts in the samples, suggesting the lack of two Ca(2+)-binding sites in the D-domains. These data suggest that the normal structure of the COOH-terminal portion of the gamma-chain including residue 375 is required for the full expression of high affinity calcium binding to D-domains, the ability to be protected by calcium against plasmic digestion, and fibrin polymerization. During these studies, we found that the NH2-terminal amino acid of the gamma-remnant in fragments D or D dimer which were obtained after prolonged digestion with plasmin is gamma-Met89.
Adult↗
Endothelial cell adhesion on polyurethanes containing covalently attached RGD-peptides.
Peptides based on cell-adhesive regions of fibronectin, Arg-Gly-Asp-Ser (RGDS), and vitronectin, Arg-Gly-Asp-Val (RGDV), were covalently bound to a polyurethane backbone via amide bonds. Nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR) spectroscopies were used to monitor the reactions. The amount of grafted peptide was determined by amino acid analysis. X-ray photoelectron spectroscopy (XPS) suggested the presence of the grafted peptide at the polymer-air interface in vacuo. Dynamic contact angle analysis showed that, in water, the peptide-grafted polyurethane surfaces were more polar than the underivatized polyurethane indicating enrichment of peptide groups at the surface. The attachment and spreading of human umbilical vein endothelial cells (HUVECs) on the underivatized and peptide-grafted polyurethanes was investigated. The GRGDSY- and GRGDVY-grafted substrates supported cell adhesion and spreading even without serum in the culture medium. The GRGDVY-grafted substrate supported a larger number of adherent cells and a higher extent of cell spreading than the GRGDSY-grafted substrate. These RGD-containing peptide-grafted polyurethane copolymers may be useful in providing an easily prepared cell-adhesive substrate for various biomaterial applications.
Amino Acids↗
Inhibition of cell adhesion by high molecular weight kininogen.
An anti-cell adhesion globulin was purified from human plasma by heparin-affinity chromatography. The purified globulin inhibited spreading of osteosarcoma and melanoma cells on vitronectin, and of endothelial cells, platelets, and mononuclear blood cells on vitronectin or fibrinogen. It did not inhibit cell spreading on fibronectin. The protein had the strongest antiadhesive effect when preadsorbed onto the otherwise adhesive surfaces. Amino acid sequence analysis revealed that the globulin is cleaved (kinin-free) high molecular weight kininogen (HKa). Globulin fractions from normal plasma immunodepleted of high molecular weight kininogen (HK) or from an individual deficient of HK lacked adhesive activity. Uncleaved single-chain HK preadsorbed at neutral pH, HKa preadsorbed at pH greater than 8.0, and HKa degraded further to release its histidine-rich domain had little anti-adhesive activity. These results indicate that the cationic histidine-rich domain is critical for anti-adhesive activity and is somehow mobilized upon cleavage. Vitronectin was not displaced from the surface by HKa. Thus, cleavage of HK by kallikrein results in both release of bradykinin, a potent vasoactive and growth-promoting peptide, and formation of a potent anti-adhesive protein.
Cations, Divalent↗
Effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide in volunteers.
The effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide (VIP) was studied in 7 healthy subjects and 8 subjects with the common cold. Before terfenadine administration, the mean plasma substance P concentration of the subjects with the common cold was significantly higher than that of the healthy subjects. The increased mean plasma substance P concentration of the subjects with the common cold was decreased after terfenadine administration. In the healthy subjects, the mean plasma substance P concentration was unchanged by terfenadine administration. The mean plasma VIP concentration of the subjects with common cold was slightly higher than that of the healthy subjects before and after terfenadine administration, with no significant difference.
Administration, Oral↗
[Seasonal fluctuations of substance P and vasoactive intestinal peptide concentrations in nasal secretions of patients with nasal allergy to Japanese cedar pollen].
Substance P (SP) and vasoactive intestinal peptide (VIP) concentrations in nasal secretions and plasma from patients with nasal allergy to Japanese cedar pollen and healthy volunteers were measured from Jan to Dec, 1991 using EIA established by us. Simultaneously, the numbers of airborne pollens of Japanese cedar and cypress were counted, and the relation to the SP and VIP concentrations in nasal secretions from the patients with nasal allergy to Japanese cedar pollen was studied. The mean SP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 81.9 +/- 48.4 fmol/mg protein, which was significantly higher than that in the non-pollination season (30.4 +/- 14.7 fmol/mg protein) (p < 0.01). Likewise, the mean VIP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 14.2 +/- 10.4 fmol/ml protein, which was significantly higher than that in the non-pollination season (4.2 +/- 3.0 fmol/mg protein) (p < 0.01). The SP and VIP concentrations in nasal secretions from the healthy volunteers were not affected by the scattering of pollens. The SP and VIP concentrations in plasma from the patients and the healthy volunteers were not affected by the scattering of pollens.
Adult↗
Neutralization of the anticoagulant effects of glycosaminoglycans by serum amyloid P component: comparison with other plasma and platelet proteins.
Serum amyloid P protein (SAP) is a heparin-binding protein that is found in blood and connective tissues including some types of vascular basement membrane. In this article we present evidence that SAP is capable of blocking the anticoagulant effects of glycosaminoglycans. SAP neutralized the catalytic effect of heparin on the thrombin-antithrombin III reaction more effectively than vitronectin, histidine-rich glycoprotein, fibronectin, and high-molecular-weight kininogen and almost as effectively as platelet factor 4. SAP also blocked the effects of heparin and dermatan sulfate on the inhibition of thrombin by heparin cofactor II. We found evidence for the formation of a high-affinity 1:1 complex between SAP and heparin and for inhibition of binding of both thrombin and antithrombin III to heparin-Sepharose by SAP. We conclude that SAP may account for much of the heparin-neutralizing capacity of plasma under some conditions and that basement-membrane-bound SAP may modulate extravascular coagulation by blocking the anticoagulant effects of basement membrane glycosaminoglycans.
Anticoagulants↗
[Retroperitoneal malignant lymphoma showing follicular type: report of a case].
We report a case of retroperitoneal follicular malignant lymphoma. A 59-year-old man visited the hospital with the chief complaint of a loss of body weight and left epigastric tumor. CT revealed a tumor, 9 x 6 cm, with non-homogeneous density in the left retroperitoneum. Since no clinical metastasis was identified, the tumor and the left kidney were resected en bloc with para-aortic lymph node dissection. Pathological diagnosis was non-Hodgkin follicular lymphoma of mixed small cleaved and large cell type with lymph node metastasis (2/23). The CHOP adjuvant chemotherapy (cyclophosphamide, adriamycin vincristine, Prednisolone) and the radiation therapy were performed after the operation. Recurrence in the mediastinal lymph node occurred 7 months after operation and radiation and the same adjuvant chemotherapy were performed and resulted in complete remission. The patient remained free of the tumor for 27 months at present.
Antineoplastic Combined Chemotherapy Protocols↗
[A case of hemangiopericytoma in the pelvic retroperitoneum].
A case of hemangiopericytoma in the pelvic retroperitoneal space is described. A 54-year-old-male had a retroperitoneal mass which had been incidentally detected during evaluation of microscopic hematuria. The pelvic arteriogram revealed an extremely hypervascular mass at the arterial phase and intensive, longlasting and well-demarcated tumor stain at the capillary phase, which were characteristic of hemangiopericytomas. Resection of the tumor was difficult due to a well developed vessel mesh around the tumor and adhesion to the surrounding tissues. The tumor weighted 45 g. The patient has remained free of disease for 29 months postoperatively. Since histopathological malignant features of hemangiopericytoma are still obscure, long term and close follow up is important.
Hemangiopericytoma↗
[Primary ureteral tumor in the residual ureter: a report of two cases].
Two cases of primary ureteral tumor in the residual ureter are reported. One was in a 40-year-old woman who had undergone simple nephrectomy for renal tuberculosis 6 years earlier. The other was in a 59-year-old man 11 years after ureterostomy for hydronephrosis. They presented with hematuria. Cystoscopic examination revealed a ureteral tumor out of the residual ureteral orifice. Computed tomographic scan showed a perivesical mass attached to the urinary bladder. It is useful for examination of ureteral stump's condition. We performed ureterectomy. The pathological study revealed the former high grade transitional cell carcinoma with squamous cell carcinoma and lymph nodes metastasis and the latter low grade transitional cell carcinoma. They have been free of disease for 5.5 years and 1.75 years, respectively. These cases are the nine and tenth reports of primary ureteral tumor of the ureteral stump in the Japanese literature.
Adult↗
Gastrin releasing peptide-like immunoreactive substance in rat mammary glands during pregnancy.
The concentration of gastrin releasing peptide-like immunoreactive substance (GRP-IS) was measured by enzyme immunoassay (EIA) in rat mammary glands during pregnancy and after delivery. The GRP-IS concentration was high in the middle stage of pregnancy (10-14 days of gestation) and decreased in late pregnancy to reach a plateau range. By using HPLC, it was shown that GRP(20-29) and GRP(16-29) were mainly present in rat mammary glands. Immunohistochemical study revealed that epithelial cells of rat mammary glands were stained intensely with antiserum GP-6201. These results suggest that GRP-IS is produced and secreted in epithelial cells of mammary glands and takes part in the proliferation, differentiation and hypertrophy of mammary glands.
Animals↗
Fibrinogen Kyoto II, a new congenitally abnormal molecule, characterized by the replacement of A alpha proline-18 by leucine.
A new case of heterozygous dysfibrinogenemia characterized by an amino acid replacement in the NH2-terminal region of the fibrin alpha-chain was found in a 27-year-old woman with a bleeding problem. Her one-stage prothrombin time and activated partial thromboplastin time were slightly prolonged, and the purified fibrinogen from this patient had a markedly prolonged thrombin or reptilase time. Release of fibrinopeptides A and B was normal, but the polymerization of fibrin monomers was impaired. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified fibrinogen under the reduced condition showed no abnormalities in the apparent molecular weights of its three chains. Reverse-phase high performance liquid chromatography (HPLC) of the lysylendopeptidase-cleaved purified A alpha-chains showed a decrease in one peptide compared with the normal amount and the appearance of an abnormal peptide peak. These peptides were treated with thrombin and further separated on HPLC. Amino acid sequence analysis of the abnormal peptide indicated that A alpha proline-18, the second residue from the NH2-terminus of the fibrin alpha-chain, was replaced by leucine. The synthetic peptide Gly-Pro-Arg-Pro inhibited both thrombin- and reptilase-induced fibrin aggregation, but Gly-Leu-Arg-Pro showed little or no inhibition under the same conditions. The discovery of this abnormal fibrinogen supports the findings that A alpha proline-18 is important as part of the polymerization site in the NH2-terminus of the fibrin alpha-chain. The propositus' mother had the same abnormal fibrinogen. This unique inherited abnormal fibrinogen was designated as fibrinogen Kyoto II.
Adult↗
A new congenital abnormal fibrinogen Ise characterized by the replacement of B beta glycine-15 by cysteine.
A new case of heterozygous dysfibrinogenemia characterized by the replacement of NH2-terminal amino acid of fibrin beta-chain was found in a 50-year-old man. Despite a prolonged thrombin time, the propositus' fibrinogen had a normal reptilase time with the normal release of fibrinopeptide A. Release of fibrinopeptide B by thrombin was strongly affected, but a very high concentration of thrombin almost completely released fibrinopeptide B with a normal elution pattern on reversed-phase high performance liquid chromatography (HPLC). Lysylendopeptidase-cleavage of purified B beta-chains analyzed on HPLC showed the decrease of one peptide compared with the normal and the appearance of an abnormal peptide peak. These peptides were treated with thrombin and further separated on HPLC. Amino acid sequence analysis of the abnormal peptide demonstrated that B beta glycine-15, NH2-terminus of the fibrin beta-chain, was replaced by cysteine. These findings will be of particular importance because they strongly support the hypothesis that the NH2-terminal portion of the fibrin beta-chain is involved in the polymerization reaction by thrombin. The propositus' daughter and two sisters had the same abnormal fibrinogen. This unique inherited abnormal fibrinogen was designated as fibrinogen Ise. During these studies, we found that a very high concentration of thrombin cleaves not only the A alpha Arg19-Val20 bond but also the COOH-terminal region of alpha-chains, which results in the generation of further degraded alpha-chains with apparent molecular weights of 44,000 or less.
Amino Acid Sequence↗
Intrathoracic fibrin glue for postoperative pleuropulmonary fistula.
Twenty cases of persistent pleuropulmonary fistula after a thoracic surgical procedure were successfully treated with fibrin glue injection into the thoracic cavity through a drainage tube. A new technique, the overlying method, which is a modification of the conventional technique of fibrin glue injection, was devised. Each patient received one to four injections (mean number, 1.6). This method resulted in closure of the pleuropulmonary fistula in all but 1 patient. Minor complications included pain in 1 patient and fever in 3 patients. A control study involving 24 patients with pleuropulmonary fistula was performed. Autoblood, OK-432, and tetracycline were used instead of fibrin glue. The fistula resolved in 12 patients. Complications after injection included pain in 15 patients, fever in 10, and occlusion of the chest tube in 4. With our new method, patients rarely exhibited pain and fever, and occlusion of the chest tube did not occur.
Adolescent↗
Clinical study of infertile males with varicocele showing no typical radionuclide blood pooling on dynamic image of scrotal scintigraphy.
A clinical study was done of 19 patients in our male infertility clinic, who were diagnosed as having a varicocele and showed atypical radionuclide accumulation in the dynamic image of scrotal scintigraphy. The semen quality was good in 26 percent and poor in 42 percent. Patients with severe congestion in the varicocele tended to be small in number. The dynamic images of the varicoceles were classified into two groups: one group with no radionuclide accumulation, and one group with patchy radionuclide accumulations. Surgical treatment was performed in patients with poor semen quality or with a long infertility period. Neither improvement in the semen quality nor impregnation was achieved postoperatively in patients who had shown no accumulation of the radionuclide in the dynamic imaging. In patients who had shown patchy radionuclide accumulations, the postoperative results were good. We concluded that preoperative dynamic imaging of scrotal scintigraphy is a good means of estimating the postoperative prognosis of fertility.
Adult↗
[Malignant fibrous histiocytoma of the urinary bladder: a case report].
A case of malignant fibrous histiocytoma (MFH) of the urinary bladder was presented. A 59-year-old man visited our hospital with a chief complaint of gross hematuria with clots. Intravenous urography revealed a filling defect on the left side of the bladder. CT scan demonstrated that the tumor invaded the bladder wall deeply. The histology of the biopsy specimens obtained by TUR was suspected to be transitional cell carcinoma. Bleeding from the bladder was so severe that a lot of units of blood transfusion were required in order to compensate for anemia before total cystectomy was performed. The tumor was hemispheric, moderately demarcated, measuring 5.5 cm x 4.0 cm x 5.5 cm, and located at the posterior wall. The histological diagnosis was malignant fibrous histiocytoma, inflammatory type, with venous invasion of tumor cells. Postoperatively, the patient received 5 courses of combination chemotherapy of adriamycin (100 mg/body, day 1) and dacarbazine (400 mg/body, day 1-5). He is alive with no evidence of local and metastatic disease 24 months after operation, in spite of the poor prognosis predicted from the histological findings. MFH of the urinary bladder is very rare. We also made a brief review of prior reports on this disease.
Antineoplastic Combined Chemotherapy Protocols↗
[Complete resection of thymic carcinoma supported by cardiopulmonary bypass].
We would like to report on a case of thymic carcinoma that could be completely resected supported by extracorporeal circulation. A 53-year-old female complaining of severe coughing and hoarseness was admitted to our hospital. Her chest X-ray film revealed an abnormal shadow in the upper mediastinum and an elevation of the left diaphragm. Chest CT and MRI showed an anterior mediastinal mass that invaded the main pulmonary artery. The preoperative histological diagnosis of thymoma was made by mediastinoscopic specimen. After 50 Gy irradiation, surgery was performed. During the operation, after resection of the left brachiocephalic vein and a part of the upper lobe of the left lung, the tumor was detached from the wall of the aorta and resected with the invaded part of the pulmonary artery supported by cardiopulmonary bypass. Reconstruction of the pulmonary wall defect was accomplished with Xenomedica. The final pathological diagnosis was thymic adenosquamous carcinoma. The postoperative course has been uneventful 24 months after surgery. Extracorporeal circulation is a useful technique in operations involving malignant diseases when complete resection is able to be accomplished.
Carcinoma, Squamous Cell↗
[Physical development of patients with spontaneous pneumothorax].
The physical development of 14 patients with spontaneous pneumothorax was studied. At the time of operation, the mean age of these 14 patients was 21.2 years, height 172.5 cm, weight 54.1 kg and Rohrer's index was 104.6, indicating marked ectomorphism. Changes in the height and body weight of these 14 patients were compared with the standard curves estimated from the national averages. The height of these patients was greater than the national average already at the age of 6 years, showed a marked increase at 11-14 years, but the increase slowed down from age 15 on. Their body weight was less than the national average at the ages of 11 and thereafter, and its increase was remarkably slower at the age 15 and beyond. Consequently, Rohrer's index was particularly low at the ages of 11-15 years. These results suggest that the ectomorphism of patients with spontaneous pneumothorax is already apparent in early childhood and is enhanced by the delay in the increase in weight as compared with height in the period of rapid physical development. The rapid increase in the vertical dimension of the thoracic cavity relative to the increase in its horizontal dimension in this period is considered to affect the intrathoracic pressure in the apical region and may promote cyst formation.
Adult↗