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Biomedical subjects

K Yamazumi

Publications and source records attributed to K Yamazumi.

At least 19 recordsLinked to original sources
PubMed2005

Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factors.

BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule implicated in the regulation of growth and malignant transformation. Constitutive activation of STAT3 is seen in several tumour derived cell lines, and in a wide variety of human malignancies. AIMS: To examine the relation between p-STAT3 (activated form of STAT3) expression and clinicopathological factors in human colorectal adenocarcinoma and adenoma. METHODS: Immunohistochemical analyses were carried out on tissues from 44 colorectal adenomas and 95 colorectal adenocarcinomas, comprising 18 intramucosal carcinomas and 77 invasive carcinomas. RESULTS: Seventy seven of these 139 samples (55.4%) showed immunoreactivity for p-STAT3. Positive staining for p-STAT3 was seen in 69 of the 95 carcinomas. Only eight of the 44 adenomas showed immunopositivity for p-STAT3, resulting in a significant difference between total adenocarcinomas and adenomas (p < 0.001). Among the 95 cases of colorectal adenocarcinoma, p-STAT3 immunoreactivity was significantly correlated with the depth of tumour invasion (p < 0.05), venous invasion (p < 0.05), lymph node metastasis (p < 0.05), and increasing stages of the Dukes' classification (p < 0.01). Expression of p-STAT3 was detected by Western blot analysis in two different cultured human colorectal carcinoma cell lines and six colon carcinoma tissue samples obtained at surgery. CONCLUSION: This is the first study to report a significant correlation of p-STAT3 expression with the depth of tumour invasion. These findings suggest that p-STAT3 expression is an important factor related to carcinogenesis and/or tumour invasion of colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1998

An activated state of blood coagulation and fibrinolysis in patients with abdominal aortic aneurysm.

BACKGROUND: Relationships between blood coagulation and the fibrinolysis system and morphology of aneurysms in patients with abdominal aortic aneurysm (AAA) are unknown. METHODS: Preoperative and postoperative evaluations of hemostatic factors such as thrombin-antithrombin III complex (TAT), D-dimer, fibrinogen/fibrin degradation products (FDP), and platelet count were performed in 36 patients with atherosclerotic AAA. As control subjects, 25 age- and sex-matched healthy volunteers were analyzed for these hemostatic factors. In all patients, morphological evaluation of AAA included the largest diameter, tortuosity, and the thickness of intraluminal thrombus to be compared with preoperative levels of hemostatic factors such as alpha-2 plasmin inhibitor-plasmin complex (PIC), thrombomodulin (TM), von Willebrand factor (vWF), tissue factor (TF), and free form of tissue factor pathway inhibitor (F-TFPI). RESULTS: The preoperative values of TAT, D-dimer, and FDP were significantly higher in AAA patients than in controls. Of all patients, 23 (64%) or 22 (58%) had TAT or D-dimer values greater than 8.2 ng/mL or 3.4 microg/mL (mean + 2SD of controls), respectively. The postoperative values of these hemostatic factors significantly improved, but were not normalized. The largest diameter of AAA correlated with the preoperative levels of TAT (r = 0.566, P = 0.001), D-dimer (r = 0.644, P = 0.0001), FDP (r = 0.561, P = 0.0009), PIC (r = 0.413, P = 0.0146), and F-TFPI (r = 0.408, P = 0.0158). We have also found that tortuosity of AAA has relation not only to the preoperative levels of fibrinolytic factors but also to the plasma F-TFPI antigen levels. On the other hand, the preoperative levels of a marker of endothelial damage, such as TM or vWF, and TF did not correlate with those of F-TFPI in all patients. The maximum thickness of thrombus in AAA significantly correlated not only with the preoperative levels of TAT, D-dimer, FDP, and PIC, but also with AAA size. CONCLUSIONS: We have found evidence that an activated state of both blood coagulation and fibrinolysis in AAA patients is associated with the morphological characteristics of aneurysms.

Aged↗
PubMed1997

[A case of hepatic arterial infusion chemotherapy for multiple liver metastasis from breast cancer].

A 52-year-old woman underwent Auchinclass' operation for breast cancer. The histological type was papillotubular carcinoma. One year and 5 months after operation, multiple liver tumors were found on the CT scan and multiple bone metastasis on MRI. The former were treated by hepatic artery infusion chemotherapy with epirubicin and 5-FU using a subcutaneous implanted pump and the latter by 50 Gy irradiation. The patient began to complain of abdominal pain and discomfort after hepatic artery infusion, so all treatment was discontinued. Six months later the patient died of respiratory failure due to pleural dissemination. No liver mass was detected, and bone metastasis was not changed in section tissues. This suggested that the therapy for a breast cancer patient with distant metastasis must be considered according to the region of recurrence.

Adenocarcinoma↗
PubMed1993

Fibrinogen Osaka IV: a congenital dysfibrinogenemia found in a patient originally reported in relation to surgery, now defined to have an A alpha arginine-16 to histidine substitution.

We discovered a congenital heterozygous dysfibrinogen in a patient and reported this case in relation to surgery some time ago (Jpn J Surg (1988) 18:43-46). Further studies on the isolated abnormal population of fibrinogen derived from this patient have revealed that fibrinopeptide A was not cleaved by ancrod, a snake venom-derived thrombin-like enzyme, but by thrombin, slowly but completely. The released fibrinopeptide A components, being the A, AY, and AP peptides, were all found to be abnormal, as evidenced by slightly earlier elution positions on high-performance liquid chromatography, compared with the normal counterparts. By analyzing their amino acid sequence, we have identified an arginine to histidine substitution at position 16 of the A alpha chain, the thrombin cleavage site. Utilizing insolubilized abnormal fibrinogen, we confirmed that the polymerization site assigned to the central E domain, the "A" site, was exposed by thrombin, but not by ancrod. This dysfibrinogen, designated as fibrinogen Osaka IV, is the second abnormal molecule with an A alpha arginine-16 to histidine substitution identified among Japanese families.

Afibrinogenemia↗
PubMed1992

Photoaffinity labeling of the primary fibrin polymerization site: localization of the label to gamma-chain Tyr-363.

Fragment D prepared from human fibrinogen was labeled specifically by photoactivation of the peptide [14C]Gly-Pro-Arg-N-(4-azido-2-nitrophenyl)Lys amide. The preparation was freed of excess labeling reagents and then reduced and alkylated. The component alpha, beta, and gamma chains were purified by chromatography on carboxymethylcellulose and the radioactivity was found to be restricted to the gamma chain. Isolated gamma chains were digested with various endopeptidases, both alone and in tandem, and the products were fractionated by gradient HPLC. The amino acid compositions of all labeled peptides led to the conclusion that the modification occurs exclusively on gamma-chain Tyr-363.

Affinity Labels↗
PubMed1992

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↗
PubMed1992

Fibrinogen Lima: a homozygous dysfibrinogen with an A alpha-arginine-141 to serine substitution associated with extra N-glycosylation at A alpha-asparagine-139. Impaired fibrin gel formation but normal fibrin-facilitated plasminogen activation catalyzed by tissue-type plasminogen activator.

An A alpha-arginine-141 to serine substitution has been identified in a homozygous dysfibrinogen, fibrinogen Lima, associated with impaired fibrin polymerization. The point mutation created an asparagine-X-serine-type glycosylation sequence, and indeed, extra, mainly disialylated biantennary oligosaccharides have been isolated from A alpha asparagine-139 of the patient's fibrinogen. This type of glycosylation sequence is unique for human fibrinogen, because the sequences shown for normal and abnormal fibrinogens are all asparagine-X-threonine types. The terminal sialic acids of the extra oligosaccharides seem to have largely contributed to the impaired fibrin gel formation, as evidenced by its correction to a near normal level by desialylation. Nevertheless, the polymerizing fibrin facilitated tissue-type plasminogen activator-catalyzed plasmin formation in a normal fashion, indicating that the initial two-stranded fibrin protofibrils had been constructed normally. Thus the impaired fibrin gel formation could be attributed to the delay in their subsequent lateral association, most probably because of the repulsive forces generated by the negative electric charge of the extra sialic acids. The substitution of a basic residue arginine to a noncharged residue serine may also have contributed to the impaired function in a similar manner or by steric hindrance in association with bulky extra oligosaccharide chains.

Amino Acids↗
PubMed1991

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↗
PubMed1991

An A alpha Ser-434 to N-glycosylated Asn substitution in a dysfibrinogen, fibrinogen Caracas II, characterized by impaired fibrin gel formation.

We have identified a unique N-glycosylated Asn substitution for a Ser at position 434 of the A alpha chain of an abnormal fibrinogen designated fibrinogen Caracas II. This dysfibrinogen was characterized by impaired fibrin monomer aggregation. Since there were 4 Thr residues immediately following the mutation, a new Asn-X-Thr/Ser-type consensus sequence, Asn-Thr-Thr arose for N-glycosylation of the Asn. The extra oligosaccharide was found to consist mainly of a disialylated biantennary structure comprising 81.9%, while a neutral and a monosialylated biantennary oligosaccharide represented only 3.6% and 14.5%, respectively. The mutation resides in the carboxyl-terminal region of the A alpha chain, which could fold back to form an extra small globular region located near the central region of the molecule (Erickson, H.P., and Fowler, W.E. (1983) Ann. N. Y. Acad. Sci. 408, 146-163; Weisel, H.P., Stauffacher, C.V., Bullitt, E., and Cohen, C. (1985) Science 230, 3124-3133). Therefore, the participation of this region, referred to as an additional central domain or an alpha domain, in fibrin gel formation is strongly implicated.

Amino Acids↗
PubMed1991

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↗
PubMed1990

Delayed intermolecular gamma-chain cross-linking by factor XIIIa in fibrinogen Asahi characterized by a gamma-Met-310 to Thr substitution with an N-glycosylated gamma-Asn-308.

In an abnormal fibrinogen with gamma-Met-310 to Thr substitution accompanied by an extra oligosaccharide attached to gamma-Asn-308, factor-XIIIa-mediated intermolecular gamma-dimer formation of fibrin was found to be markedly delayed. The delayed gamma-dimer formation was not due to impaired fibrin polymerization because the fibrinogen gamma-chain also failed to be efficiently cross-linked by factor XIIIa. Since fluorescent amine was normally incorporated into the abnormal gamma-chain by factor XIIIa, we conclude that the abnormal molecules were unable to align their gamma-chains in an anti-parallel fashion because of inaccessibility of the molecules with a profoundly perturbed conformation near the carboxyl terminal region of the gamma-chain included in the D domain.

Fibrinogen↗
PubMed1990

[Changes in the liver weight in the elderly].

To elucidate the effect of aging on liver weight in the elderly, 582 elderly cases (male 291, female 291), were selected from 2000 elderly autopsied cases on the basis of being free from pathological findings affecting liver weight. Both liver weight and its ratio to body weight decreased with age, and influenced by obesity; the former increased and the latter decreased in obese cases. Analysis according to the degree of obesity also showed decrease of liver weight and is ratio to body weight with age. Comparison between males and females of the same decade revealed the tendency that in females the liver weight was low, while liver weight.body weight ratio was high. The same results were obtained by analysis based on the degree of obesity.

Aged↗