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Biomedical subjects

E Shiba

Publications and source records attributed to E Shiba.

At least 73 records · Page 4Linked to original sources

Radical mastectomy with parasternal node dissection or radiation to the parasternal region for breast cancer of medial or central location.

In order to establish a therapeutic approach for primary breast cancer of medial and central origin, we reviewed 183 patients who had been treated by one of the following three modalities at the Second Department of Surgery, Osaka University Medical School between January, 1965 and December, 1980. Group A (n = 70): standard radical mastectomy alone; Group B (n = 34): standard radical mastectomy followed by postoperative irradiation to the parasternal and supraclavicular regions, and; Group C (n = 62): extended radical mastectomy that included removal of the parasternal lymph nodes. The background factors of the three groups were not significantly different. The overall survival five and ten years following surgery in the three groups were 91 percent and 79 percent in group A, 82 percent and 67 percent in group B, and 82 percent and 70 percent in group C, respectively, showing no significant difference in overall survival among the three groups. When the patients were classified according to the extent of axillary lymph node involvement, there was no difference in survival among the three treatments in patients who had less than three lymph node metastases in the axilla. However, treatment of the parasternal lymph nodes improved survival in the patients who had more than four lymph node metastases in the axilla. Parasternal lymph node involvement definitely worsened the prognosis, showing it to be a good prognostic factor. Thus, extended radical mastectomy should be considered for patients with breast cancer of medial or central location, when extended axillary lymph node involvement is found.

Adult↗

Ultrastructural analysis of pseudo-intimal hyperplasia of polytetrafluoroethylene prostheses implanted into the venous and arterial systems.

To evaluate and compare the pathogenesis of pseudo-intimal hyperplasia (PH) of venous and arterial prostheses, a segment of the inferior vena cava (n = 16) or abdominal aorta (n = 16) was substituted by a 3 mm internal diameter polytetrafluoroethylene tube graft (PTFE, 3 cm long, 30 microns in nodal distance) in albino rabbits. At designated time intervals (3-28 days) after the replacement, graft patency was examined and the dry weights of the intraluminal deposits measured as an indicator of the degree of PH. The harvested grafts were then subjected to an ultrastructural analysis by means of light microscopy (LM), and scanning electron and transmission electron microscopy (SEM, TEM). All the grafts remained patent during the entire observation period. The PH judged by the dry weight was significantly more extensive in the venous than in the arterial prostheses. The PH on day 28, observed by light microscopes was apparently most extensive in the mid-portion of venous prostheses but in the arteria prostheses it was mostly seen at the anastomotic sites. The lining of the intraluminal surface of the prostheses with endothelial-like cells observed by SEM was faster and more extensive in venous than in arterial prostheses. The process of PH in venous prostheses observed by TEM may be divided into the following steps: early thrombosis, phagocytosis of the thrombus, appearance of fibroblasts, growth of endothelial-like cells, appearance of smooth muscle cells, and pseudointimal thickening and proliferation of fibroblasts producing collagen fibrils. The process in arterial prostheses was essentially identical to that in venous prostheses but was much slower and less extensive. From these observations, it was concluded that the formation of PH occurs much faster in venous than in arterial prostheses, although the mechanism of PH is mostly identical in venous and arterial prostheses.

Animals↗

Species differences in platelet aggregation induced by platelet-activating factor (PAF).

Species differences in platelet aggregation induced by platelet-activating factor (PAF) were investigated by using the same procedure of platelet preparation and biological assay. Washed platelets of six different species (horses, dogs, rats, rabbits, sheep and guinea pigs) were prepared employing the same method and platelet aggregation was induced by C16-PAF. Horse platelets were most sensitive to PAF (8.0 x 10(-12) M) and rabbit platelets activated by 5.0 x 10(-11) M PAF were also sensitive enough to detect PAF in clinical samples.

Animals↗

The effects of okadaic acid and calyculin A on thrombin induced platelet reaction.

Okadaic acid and calyculin A, specific and cell permeable inhibitors of protein phosphatase 1 and 2A, inhibited aggregation, secretion and delta [Ca++]i in thrombin stimulated platelets. The inhibitory effect of calyculin A (IC50: 3.6-4.8nM) was about two hundred times more potent than that of okadaic acid (IC50: 0.8-1.3 microM), which is consistent with the difference of the reported Ki values for protein phosphatase 1. These phosphatase inhibitors and PGI2 synergistically enhanced the phosphorylation of 50kDa protein (P50), which is solely related to the inhibition of platelet reaction. These results indicate that serine/threonine protein phosphatase 1 might play a role in platelet activation.

Adenosine Triphosphate↗

[A case of advanced breast cancer with multiple organ metastases successfully treated by tamoxifen].

A 66-year-old postmenopausal woman presented in June 1991 with a giant ulcerated left breast tumor. She had discovered the tumor two years previously, but had never visited any medical institution. She was diagnosed as advanced breast cancer with multiple lung metastases, bone metastasis, and both supraclavicular lymph node metastases by physical examination, fine needle aspiration cytology, chest X-P, and bone scintigraphy. Incisional biopsy, performed to confirm the histological type of breast cancer and to evaluate estrogen and progesterone receptor (ER and PgR) status, revealed solid-tubular carcinoma. Both ER and PgR were highly positive at 322.6 and 228.0 fmol/mg protein, respectively. Therefore, endocrine therapy was chosen to treat this advanced breast cancer patient, although she had multiple organ metastases. Twenty mg of Tamoxifen a day was administered per os. After treatment with tamoxifen, the size of ulceration started to decreased and the dyspnea caused by multiple lung metastases was reduced. Eight weeks after, she showed partial response (PR) determined from the size of the ulceration and chest X-P. She has been maintaining PR for more than 9 months. Thus, Tamoxifen was shown to be very effective for this case of advanced breast cancer with multiple organ metastases.

Adenocarcinoma↗

Membrane binding and autolytic activation of calpain-I in human platelets.

The binding of calpain-I (Ca2+ activated neutral protease with high Ca2+ sensitivity) to the membranes of human platelets and the subsequent autolytic activation of calpain-I were analyzed by an immunoblot technique. In A23187 stimulated platelets, cytosolic calpain-I translocated to the membranes with autolysis in a Ca2+ dependent manner and simultaneously underwent autolysis. Although calpeptin, a cell permeable calpain inhibitor, inhibited autolysis of calpain-I, it was unable to prevent the translocation of calpain-I. In a cell re-constituted system, the membrane binding of calpain-I was also Ca2+ dependent and was significantly inhibited by a substrate of calpain. It was suggested that the binding of calpain-I to the membranes required the substrate binding site of this enzyme.

Biological Transport↗

Proteasome and its novel endogeneous activator in human platelets.

Proteasome, a high molecular weight multicatalytic protease, was purified from the cytosolic fraction of human platelets for the first time. The biochemical properties of the enzyme including substrate specificity, optimal pH and effects of various inhibitors were almost identical with those of other cells. During the purification with a Heparin-Sepharose chromatography, a novel endogenous activator of the protease was identified and was partially purified. The activator enhanced both chymotrypsin or trypsin like activities of the proteasome in a dose related manner and was inactivated by heating at 56 degrees C for 30 min. This newly identified activator may serve as an important regulator or cofactor of intracellular activities of the proteasome.

Amino Acid Sequence↗

The possible involvement of platelet activation in endotoxin-induced renal insufficiency in a rabbit model.

The effects of the anticoagulants, heparin and low molecular weight heparin (LMWH), and the antiplatelet agents, prostaglandin E1 (PGE1) and aspirin, on endotoxin-induced renal insufficiency not induced by prerenal factors, were investigated using rabbits to evaluate the clinical usefulness of these drugs and their possible involvement in the activation of hemostasis in renal insufficiency. The intravenous administration of PEG1, at 0.4 microgram/kg/min, or aspirin, at 5 mg/kg, significantly restored all the parameters of renal function measured in the present study, namely, effective renal plasma flow, glomerular filtration rate and urine N-acetyl-beta-D-glucosaminidase, as well as histological renal ischemic changes. On the other hand, neither heparin nor LMWH, even at a high dose, improved any parameter. As the antiplatelet effect is the common property of PGE1 and aspirin, it is suggested that the activation of platelets may be prerequisite to the occurrence of renal insufficiency induced by endotoxin. The results of this study thus show that PGE1 or aspirin may be applied in clinical use for renal insufficiency complicated by sepsis or endotoxemia.

Acetylglucosaminidase↗

Antibody-detectable changes in fibrinogen adsorption affecting platelet activation on polymer surfaces.

Reactivity of platelets with an artificial surface exposed to whole blood is correlated with the concentration of adsorbed fibrinogen detectable by antifibrinogen antibodies. To examine the effect on platelets of the organization (distribution, orientation, conformation) of fibrinogen adsorbed on a hydrophobic surface, we studied the binding of polyclonal and monoclonal antifibrinogen antibodies to polyalkyl methacrylate polymers previously exposed to purified fibrinogen solution or diluted plasma and compared the results with platelet retention in methacrylate bead columns. There was an increase in platelet retention following diluted plasma pretreatment, which was eliminated by a polyclonal antibody against fibrinogen or against a gamma-(395-411) peptide from fibrinogen and was reduced by monoclonal antibodies (4A5, 4-2) against other COOH-terminal gamma-chain epitopes. Monoclonal antibody 10E5 against the fibrinogen receptor GpIIb/IIIa totally inhibited platelet retention in the bead columns. Our data suggest that different methacrylate polymers induce different changes in adsorbed fibrinogen, which may interfere with its interaction with platelets, and that platelet retention in a methacrylate bead column involves interaction of the COOH-terminal end of the gamma-chain of adsorbed fibrinogen with platelet GpIIb/IIIa receptors.

Adsorption↗

Effects of transcatheter hepatic arterial embolization on coagulation and fibrinolysis in patients with hepatocellular carcinoma.

The changes in coagulation and fibrinolysis were studied in cases of hepatocellular carcinoma with (n = 20) and without (n = 8) transcatheter hepatic arterial embolization (TAE). The plasma levels of thrombin-antithrombin III complex (TAT) and alpha 2 plasmin inhibitor complex (PIC) were significantly elevated after TAE, concurrently with a decrease in antithrombin III and antiplasmin (alpha 2-plasmin inhibitor) levels. The elevation of TAT was most significant (2.4-fold of the pre-TAE level) on day 3, whereas that of PIC was relatively less (1.3-fold on day 3). Tissue plasminogen activator in blood was also significantly increased on day 1, but it was decreased thereafter, although plasminogen activator inhibitor (PAI) remained high for at least 7 days after TAE. In contrast, such hematological changes were not observed in patients without TAE. Thus, both coagulation and fibrinolysis were activated after TAE, but its effect on fibrinolysis was less prominent, due probably to the increased synthesis of PAI.

Adult↗

[A comparative study of intra-arterial infusion chemotherapy and systemic chemotherapy in the treatment of locally advanced breast cancer].

A comparative randomized study of intra-arterial infusion chemotherapy (IA) and systemic chemotherapy (IV) was carried out on 41 patients with locally advanced breast cancer, and the following results were obtained. 1) The response rate of primary lesions to IA (63.2%) was better than that of IV (40.9%). 2) In the patients treated with IA, grade of leukopenia, as well as the percentage of gastro-intestinal disorders, was low. 3) More prolonged follow-up studies are required on the therapeutic effects on micrometastasis. The author confirmed that IA was an efficacious neoadjuvant therapy in terms of down staging of locally advanced breast cancer.

Breast Neoplasms↗

Characteristics of various synthetic peptide calpain inhibitors and their application for the analysis of platelet reaction.

Calpeptin (a cell permeable synthetic peptide calpain inhibitor) inhibited the generation of thromboxane B2 (TxB2) by the direct inhibition on Tx synthetase in platelets at the concentrations more than 30 microM. Calpeptin, its analogues and E-64d (EST) were further examined with regard to cell permiability and inhibitory spectra. Among all compounds, only calpeptin inhibited the degradation of substrate proteins of calpain with negligible effect on TxB2 generation in intact platelets at the concentrations less than 30 microM. These concentrations of calpeptin did not inhibit the platelet aggregation, the elevation of [Ca2+], nor the formation of inositol 1,4,5-trisphosphate (IP3) in thrombin or collagen activated platelets. These results indicate that calpain dose not participate in the process of platelet activation induced by thrombin or collagen.

Arachidonic Acids↗

Activation of coagulation and fibrinolysis during surgery, analyzed by molecular markers.

Activation of hemostasis during surgery was investigated in 30 elective cases, who underwent either gastric (group G) or hepatic (group H) resection by a serial determination of various molecular markers such as fibrinopeptide A (FPA), fibrinopeptide B beta 15-42 (B beta 15-42) D-dimer, thrombin-antithrombin III complex (TAT) and plasmin-alpha 2 plasmin inhibitor complex (PIC). In both groups, the values of FPA and TAT were significantly elevated intraoperatively, indicating an occurrence of hypercoagulable state. The degree of the elevation was more marked in group H, probably due to greater tissue damage during hepatic resection. Also in both groups, the values B beta 15-42 and PIC were significantly increased during surgery, while the amount of D-dimer was within normal range in most cases, indicating the occurrence of the primary fibrinolysis. These findings are compatible with our previous observations on the postoperative changes in hemostasis. There were statistically significant but variable correlations between the values of fibrinopeptides and the enzyme-inhibitor complexes. The absolute values of the molecular markers of fibrinolysis were always higher than those of coagulation, suggesting that a considerable amount of plasmin, rather than thrombin, is released by surgical tissue damages.

Antithrombin III↗

The pathogenesis of thrombosis in venous prostheses.

To evaluate the pathogenesis of thrombosis formation in synthetic venous grafts, the inferior vena cava of rabbits were replaced by woven Tetron (polyethylene terephtalate) grafts. Six animals were assigned as controls without medication (Group A), and 48 animals were randomly assigned to experimental groups as follows: ticlopidine hydrochloride (100 mg/kg/day) was administered orally from 5 days prior to operation to the end of the experiment (Group B); warfarin sodium (0.33 mg/kg/day) was given orally for the same period (Group C); and a combination of ticlopidine hydrochloride (50 mg/kg/day) and warfarin sodium (0.16 mg/kg/day) was administered for the same period (Group D). All the grafts in group A occluded within 3 h. All grafts harvested from groups B and D remained patent at least until the twenty-eighth day after grafting but the lumen was narrowed by intimal hyperplasia. Although the grafts from group C were patent at the seventh day, all grafts occluded with intimal hyperplasia on day 14 and day 28. The dry weight of thrombus in the graft in group B and group D was 39 +/- 3 mg and 30 +/- 2 mg, respectively on day 28. These figures were significantly lower than that of the control group 59 +/- 9 mg at 5 h after the initial heparinisation. Ultrastructural studies with scanning electron microscopy showed that the thrombus in the graft of the control group was composed of platelet aggregates anchored to synthetic fibres and of erythrocytes entrapped in the fibrin network. By day 7, in the groups modified with drugs, sheets of endothelial-like cells extended across both suture lines from the host stumps and extended to the middle of the graft thereafter. Light microscopy revealed that the initimal hyperplasia in groups B, C and D on day 28 were mainly composed of fibroblasts, myoblasts, collagenous fibres and micro-capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗