Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 19 recordsLinked to original sources

PubMed1992

Plasminogen activators and plasminogen activator inhibitor 1 before and after venous occlusion of the upper limb in thromboangiitis obliterans (Buerger's disease).

Plasma levels of plasminogen activators (t-PA, u-PA) and their inhibitor (PAI-1) were studied in patients suffering from Buerger's disease and healthy volunteers before and after 15 minutes of venous occlusion test. The baseline levels of t-PA in group of patients did not differ from those of controls. On the contrary patients with Burger's disease showed a marked increase in u-PA antigen concentrations with concomitant decrease in PAI-1 antigen levels. During venous stasis t-PA antigen concentrations increased in all subjects, however it was much pronounced in controls. Venous occlusion resulted in significant decrease in free PAI-1 levels in the group of patients only. In conclusion, Buerger's disease is associated with the endothelial derangement with increased u-PA release and decreased PAI-1 release, which does not influence the function of fibrinolytic system. The fact that the reduced response of the endothelium to release t-PA after venous stasis goes in parallel with marked decrease in PAI-1 antigen levels seems to suggest that patients suffering from Buerger's disease are not at high risk of intravascular fibrin deposition.

Arm↗

PubMed1992

Fibrinolytic and anticoagulant activities of highly sulfated fucoidan.

A series of fucoidan [sulfated poly(L-fucopyranose)] derivatives were prepared by chemical sulfation and desulfation, and they were tested for their abilities to stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation, clot lysis, and the inhibition of fibrin polymer formation. The magnitude of their activities was dependent upon the degree of sulfation. A striking feature of the sulfated fucoidan was that, unlike heparin, it stimulated t-PA-induced plasma clot lysis by protecting plasmin activity from alpha 2-plasmin inhibitor and decreased the rate of fibrin polymer formation. The inhibition of hyaluronic acid-mediated enhancement of fibrin clot formation was also observed with the fucoidan derivative. We also showed that highly sulfated fucoidan prevents significantly endotoxin-induced hepatic vein thrombosis in the hyperlipemic rat model. The present results are the first to describe the fibrinolytic and anticoagulant activities of fucoidan, and thus may provide useful clues for the development of an ideal thrombolytic agent.

Animals↗

PubMed1992

Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues.

The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis.

Enzyme-Linked Immunosorbent Assay↗

PubMed1992

Portal vein thrombosis after splenectomy successfully treated by an enormous dosage of fibrinolytic agent in a short period: report of two cases.

Portal vein thrombosis (PVT) after splenectomy in a patient with portal hypertension occurs with unusually high frequency. Recently, two patients with PVT following splenectomy were treated by fibrinolytic therapy with an enormous dosage of urokinase (UK) in a short period. PVT was quickly dissolved without side effects and the patients are now doing well without any recurrence of PVT. Therefore, when there is no evidence of bowel infarction, fibrinolytic therapy with an enormous dosage of UK over a short period is deemed to be both effective and essential as a conservative therapy for PVT.

Adult↗

PubMed1992

Aggressive repeat liver resection for hepatic metastases of colorectal carcinoma.

Although hepatectomy for liver metastases from colorectal carcinoma is an effective treatment, recurrence in the liver is still the most common site after hepatectomy. Thirty patients underwent hepatectomy for hepatic metastases and 17 of them had recurrence in the remnant liver during the following 12-year period. Six of the 17 patients underwent a removal of isolated hepatic recurrences. Two of the six patients underwent a third hepatectomy, and three patients underwent partial lung resection on a total of five occasions. There were no operative deaths while complications after a third hepatectomy contributed to a high morbidity rate of 40 per cent. The mean length of survival of the six patients was 28.5 months from the second hepatectomy. The prognosis of the six patients who underwent a repeat hepatectomy was significantly better than that of patients with unresectable recurrence after an initial hepatectomy (p less than 0.01). The overall 5-year survival of 29 patients excluding one in-hospital death was 44.7 per cent. Our results reveal that aggressive removal of isolated and resectable recurrent disease has the potential to improve the prognosis of selected patients with metastatic cancer.

Adult↗

PubMed1992

Extension incision for renal carcinoma including invaded vena cava and right lobe of liver.

We report on a thirty-five-year-old woman with renal cell carcinoma who successfully underwent right radical nephrectomy and extended right hepatic lobectomy with resection and reconstruction of inferior vena cava (IVC). A temporary bypass was placed between the infrarenal IVC and right atrium using a heparin-coated synthetic tube. The tumor was resected en bloc including right kidney, adrenal gland, hepatic lobe, and IVC. The IVC was reconstructed using an expanded polytetrafluoroethylene (EPTFE) graft. Her postoperative course was uneventful with no signs of recurrence four years after surgery.

Adult↗

PubMed1992

Causes and mechanism of autoimmune disease: cyclosporin A as a probe for the investigation.

Organ-specific autoimmune disease can be elicited in rodents by manipulating the thymus/T cells. For example, elimination of a particular T-cell subset causes organ-specific autoimmune diseases, such as thyroiditis and gastritis, in otherwise normal mice. Environmental agents can cause similar autoimmune diseases by affecting the thymus/T cells. Cyclosporin A (CsA), a potent immunosuppressive drug, is an example. When a particular strain of newborn mice are daily administered with CsA for a limited period, they spontaneously develop organ-specific autoimmune disease, such as gastritis with anti-parietal cell autoantibodies, later in life. CsA abrogates the production of CD4+T cells and CD8+T cells in the thymus. Consequently, these T cells are substantially depleted from the peripheral lymphoid organs, especially when the drug is administered from the day of birth. The autoimmune disease is prevented when CsA-treated newborn mice are inoculated with splenic T cells from normal syngeneic adult mice. On the other hand, removal of the thymus immediately after neonatal CsA treatment produces autoimmune disease with a higher incidence and in a wider spectrum of organs, i.e., thyroiditis, sialoadenitis of the salivary gland, gastritis, insulitis of the endocrine pancreas, adrenalitis, oophoritis, or orchitis. Each autoimmune disease is accompanied by the development of circulating autoantibodies specific for the corresponding organ-specific antigens. These findings taken together indicate that CsA causes autoimmune disease not by affecting the target self-antigens, but by interfering with a thymus/T cell-dependent control mechanism on the production/expansion of pathogenic self-reactive T cells. Various other environmental insults (such as ionizing radiation or virus) can also cause similar autoimmune diseases, presumably by a similar mechanism.

Animals↗

PubMed1992

An enzyme-linked immunosorbent assay for the detection of plasminogen activator-induced fribrin clot lysis in a circulating plasma system.

A technically easy and sensitive method for the evaluation of the fibrinolytic potency of plasminogen activator in a circulating plasma system was developed. A circulating apparatus was prepared by connecting silicone tubes with two separate chambers. Human plasma and plasminogen activator were allowed to circulate from one chamber through a peristaltic pump into another one which contained biotin-labeled fibrin clot. The extent of fibrinolysis was evaluated on streptavidin-coated microtiter plates by measuring the amount of the avidin-bound fibrin degradation products with peroxidase-linked antibody. The detection limit of the fibrinolytic products was 1.5 ng/ml. The present method dose not require any specialized equipment and is also applicable to a low-cost routine measurement of the thrombus selectivity of plasminogen activator.

Bacterial Proteins↗

PubMed1992

[Antihypertensive effect of felodipine, a new calcium antagonist].

The antihypertensive effect of felodipine was examined in various hypertensive animal models. In spontaneously hypertensive rats, felodipine administered singly at 0.1-1.0 mg/kg (p.o.) had a dose-dependent antihypertensive effect. Nifedipine was effective at 1 mg/kg. In the repeated oral administration experiment, both the maximum decrease in blood pressure and duration of the effect increased gradually and reached steady levels at 3 weeks of administration, which were maintained thereafter. Similar results were noted with nifedipine, but felodipine was longer-acting (4-6 hr) in the steady state than nifedipine (1-2 hr). No development of tolerance was observed during the administration period. In DOCA-salt and renal hypertensive (2K1C) rats, felodipine at 0.1-0.5 mg/kg (p.o.) was superior to nifedipine in the maximum decrease in blood pressure and duration of the effect. Felodipine up to 1 mg/kg (p.o.) caused no significant heart rate increase in any rat model. In renal hypertensive (2K2C) dogs given felodipine at 0.2-0.5 mg/kg (p.o.), the effect lasted for 2 hr after injection. This felodipine effect was stronger and longer lasting than the nifedipine one. At 0.5 mg/kg of felodipine, the heart rate was transiently increased. The present results show that felodipine has a stronger and long-lasting antihypertensive effect than nifedipine in the hypertension models.

Administration, Oral↗

PubMed1992

[A study of the humoral immunity of mice injected with beryllium chloride].

We studied changes of humoral immunity, such as complement pathway activity, C3 contents and contents of immunoglobulin, in mice injected subcutaneously with BeCl2 or CuCl2 once a week for 12 weeks. Mean body weights of JCL: ICR female mice were approximately 30g in control mice (control group; n = 7), in mice injected with Be (Be group; n = 8) and in mice injected with Cu (Cu group; n = 8). Values of classical complement pathway activity (CH50) were 18.8 +/- 1.4 U per ml, 15.3 +/- 1.8 U per ml and 16.7 +/- 1.3 U per ml in the control group, Be group and Cu group, respectively. The CH50 values of Be and Cu groups were significantly lower than that of the control group (P < 0.01). In contrast, values of alternative complement pathway activity (ACH50) and contents of C3 were almost constant in the three groups. The immunoglobulin content in the Be group tended to increase. The activity of alanine aminotransferase in the Be group was markedly higher than that in the control group (P < 0.05), and the aspartate aminotransferase activity was also high. The CH50 value of mice injected with a small amount of Be once a week over a 12-week period decreased markedly, although either the ACH50 value or C3 content was the same as in the control group. The immunoglobulin content somewhat increased in the Be group. These results suggest the possibility that immune complex is induced by Be.

Animals↗

PubMed1992

The mouse ligated intestinal loop assay for the studies on enteroinvasive Escherichia coli.

Enteroinvasive Escherichia coli exhibited a positive reaction in the mouse intestinal loop assay except for noninvasive mutant strains. These mean values of fluid weight per gut length of mouse loops inoculated with enteroinvasive E. coli were significantly higher than that given by brain heart infusion broth. Oedema and swelling in all positive loops, increased bacterial cell numbers within intestinal loops were observed.

Animals↗

PubMed1992

[The comparison of postoperative multiple organ failure with arterial disease to that with gastrointestinal cancer].

The clinical features of 22 postoperative multiple organ failure (MOF) patients, comprised of 8 with arterial disease (A-MOF) and 14 with gastrointestinal cancer (G-MOF), were investigated. Differences in the operative time, blood loss, and mortality were not significant. The initial organ impaired was the lungs in 78.6% of G-MOF patients and the heart or kidneys in all A-MOF patients. Infection developed in over 80% of both groups. In many A-MOF patients, the pneumonia or septicemia developed secondary to organ failure, while intraabdominal infection triggered respiratory failure in many G-MOF patients. Our organisms in infected specimens and their antibiotic sensitivities was valuable for the early administration of effective antibiotics. Upper gastrointestinal tract bleeding was important in the prognosis of both groups and occurred more frequently in A-MOF than in G-MOF patients. Consumption coagulopathy in A-MOF patients and DIC induced by infection in G-MOF patients mainly caused such bleeding. Preoperative administration of heparin was effective in improving coagulopathy. Furthermore, measurement of intramural pH with tonometer in the stomach and gastric irrigation with oxygenated perfluorochemicals were effective in the prediction and prevention of gastrointestinal bleeding.

Aged↗

PubMed1992

[Principle of treatment of intermittent claudication due to arteriosclerosis obliterans--reconstruction or conservative treatment].

MATERIALS AND METHODS: Two hundred and one patients of arteriosclerosis obliterans (ASO) with intermittent claudication (IC) were studied. Improvement of IC, score of return to social life, change of life condition and prognosis were compared between the two groups of reconstructive and conservative treatment. RESULTS: Improvement of IC was seen in 88.0% of the patients in the group of reconstruction and only 30.4% in the conservative treatment group. In the reconstructive group, the score of return to social life improved from 2.10 to 1.31 and the score of life condition also improved from 2.71 to 1.66. However in the conservative treatment group these score showed no significant improvement. Moreover the long term mortality rate was lower in the treatment group of reconstruction. CONCLUSION: The arterial reconstruction for IC is significant for improving the quality of life and exerts a favorable effect on life prognosis.

Aged↗

PubMed1992

[Effects of surgical stress on peripheral venous functions].

Postoperative changes in peripheral venous functions were determined by Ga-In strain gauge plethysmography in 28 surgical patients, and central venous functions and urine catecholamine levels were also measured. The results were as follows: 1. The maximum venous outflow (MVO) and arterial blood inflow volume (AF) of the healthy arms tended to increase with age, but showed no sex or right-to-left difference. 2. MVO, AF and venous distensibility were decreased postoperatively, and the decreases were greater in the patients with major surgery than in those with minor surgery. 3. MVO in the patients with high urine levels of adrenaline and noradrenaline showed a greater decrease than those in normal subjects, and the majority of these patients were found to have had major surgery. There was a negative correlation between the urine noradrenaline level and MVO. 4. The decrease in peripheral venous functions preceded the decrease in central venous functions. 5. The postoperative decrease in peripheral venous functions was considered to be the result of active vasoconstriction due to hypersecretion of catecholamines caused by surgical stress and increase in the extravascular pressure. 6. Measurement of venous functions of the arm may be a good parameter for detecting circulatory disturbances due to surgical stress.

Adult↗

PubMed1991

A DBL-homologous region of the yeast CLS4/CDC24 gene product is important for Ca(2+)-modulated bud assembly.

The CLS4/CDC24 is essential for the budding process of the yeast Saccharomyces cerevisiae. Disruption of the CLS4/CDC24 gene is lethal, and expression of the CLS4 product under the control of the GAL1 promoter is sufficient for cellular growth. The CLS4 product is detected in yeast cell lysate with an apparent molecular mass of 93 kD (854 amino acid residues) and shows homology with the human DBL oncogene product. Temperature-sensitive cdc24-1 mutation is located in the N-terminal portion of the protein whereas Ca(2+)-sensitive cls4-1 mutation is present after the DBL-homologous region (amino acid residues 281-518) near the putative Ca(2+)-binding site. Mutations within the DBL-homologous region are responsible for the Ca(2+)-sensitive phenotype. Thus the CLS4 gene product seems to have several functional domains within the molecule essential for bud assembly.

Amino Acid Sequence↗

PubMed1991

Increase in levels of plasminogen activator and type-1 plasminogen activator inhibitor in human breast cancer: possible roles in tumor progression and metastasis.

We measured antigen levels of two kinds of plasminogen activators, tissue type plasminogen activator (t-PA) and urokinase type plasminogen activator (UK), as well as their primary inhibitor, type-1 plasminogen activator inhibitor (PAI-1) in the tissue extracts of benign and malignant breast tumors. Tumor tissues of 36 fibroadenomas and 39 breast cancers were examined. t-PA levels were not different in both groups. Malignant tumors contained the significantly higher levels of UK than benign tumors (p less than 0.001). Furthermore in breast cancer tissues, UK antigen levels of tumors with axillary lymph node involvements were significantly higher than those of tumors without lymph node involvements (p less than 0.05). PAI-1 antigen levels of breast cancer tissues were dramatically higher than those of fibroadenoma (p less than 0.001). PAI-1 levels of node positive carcinomas showed also values significantly higher than node negative ones (p less than 0.01). When we divided cancer tissues into three groups as node negative tumors, tumors with positive axillary nodes fewer than four and tumors with four or more positive nodes, PAI-1 levels increased corresponding to the progression of lymph node involvements (p less than 0.05). Immunohistochemical studies, using mouse monoclonal antibodies to human UK and PAI-1, showed that those immunoreactivities were diffusely distributed in the cytoplasm of human breast cancer cells. Their staining patterns were very similar to each other.

Adenofibroma↗

PubMed1991

Influence of hepatitis B virus infection and age on mode of growth of hepatocellular carcinoma.

According to the extent of hepatic involvement of the tumor and that of portal vein invasion at the time of initial diagnosis, patients with hepatocellular carcinoma (HCC) were grouped into three or four groups. Correlations among the extent of hepatic involvement, extent of portal vein invasion, and prevalence of hepatitis B surface antigen (HBsAg) and age distribution were examined. The extent of hepatic involvement of the tumor and that of portal vein invasion were significantly greater in patients with positive HBsAg compared with findings in the negative patients (P less than 0.001). For cases of both positive and negative HBsAg, patients with a more extensive HCC were significantly younger. Results of the multivariate logistic regression analysis showed that hepatitis B antigenemia and younger age were statistically significant and independent positive predictors of extensive HCC. These results strongly suggest that hepatitis B surface antigenemia and age play an important role in the growth mode and the kinetics of HCC in Japanese patients.

Adult↗

PubMed1991

Detection of neutral sugars in purified type G botulinum progenitor toxin and the effects of some glycolytic enzymes on its molecular dissociation and oral toxicity.

Arabinose and galactose were detected in purified type G botulinum toxin (Mr about 500,000) of Clostridium argentinense. The i.p. LD50/mg N of type G progenitor toxin was one-tenth, but the oral LD50/mg N twice that of type A-L toxin. The lysozyme-, endo-beta-galactosidase-, and N-glucanase-treated toxins each had a molecular mass of about 300,000. The oral toxicity of the endo-beta-galactosidase or N-glucanase-treated toxin was one-fifth that of untreated progenitor toxin. On DEAE-Sephadex chromatography, the N-glucanase-treated toxin dissociated into two fractions, nontoxic and toxic. SDS-PAGE of the toxic fraction showed a single band with a Mr of about 150,000, and after dithiothreitol treatment, two bands with Mr of 100,000 and 50,000.

Administration, Oral↗