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Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 145 records · Page 8Linked to original sources

Correlation between polyploidy and auxotrophic segregation in the imperfect yeast Candida albicans.

In order to clarify the relationship between polyploidization and the capability of phenotypic switching in the imperfect yeast Candida albicans, two types of variants were isolated as segregants from a fusant, which produced a proportion of the cell population with a higher ploidy than the rest, either in a temperature-dependent or -independent manner, when incubated at low (28 degrees C) and high (37 degrees C) temperatures. In the case of the temperature-dependent type of variants, high-ploidy cells appeared at 37 degrees C but rarely at 28 degrees C. This phenotype was named Pldts (temperature-sensitive polyploidization), and the temperature-independent phenotype was called Pld-. The appearance of high-ploidy cells in the culture of the Pldts strain at 37 degrees C was accompanied by a significant increase in the frequency of auxotrophic variants; these variants probably occur as a result of segregation of auxotrophic markers from the heterozygous to the homozygous state. Both Pldts and Pld- phenotypes were recessive in a fusion with a Pld+ parent. An adenine auxotrophic marker (ade1) was introduced into a Pldts strain in a heterozygous state, and the individual high-ploidy cells of this strain, grown at 37 degrees C, were micromanipulated to form colonies, which consisted of red and white sectors appearing at high frequency on a pink background. When the ade1 auxotrophy was introduced into Pld- strains, frequently sectored colonies were produced. These results suggested an increased level of chromosome missegregation in both types of Pld mutants. Analyses by pulsed-field gel electrophoresis of Ade-segregants, derived from a micromanipulated high-ploidy cell of a Pld(ts) strain, suggested the occurrence of nonreciprocal recombination, some of which includes chromosome loss.

Adenine↗

Defense effects of a traditional Chinese medicine (sho-saiko-to) against metabolic disorders during endotoxemia; approached from the behavior of the calcium ion.

The present study was carried out as an approach from intracellular Ca2+ to clarify the preventive effects of a traditional Chinese medicine, Sho-saiko-to (Kampo prescription, TJ-9), against various metabolic disorders during endotoxemia. In this experiment, we estimated the cytosolic-free Ca2+ concentration ([Ca2+]i) in liver single cells using a photonic microscope system. The [Ca2+]i in a single liver cell of endotoxin (6 mg/kg, i.p.)-injected mice was greater at 18 h post-intoxication than that in the control, whereas the administration of endotoxinin to TJ-9 (500 mg/kg/d, p.o.)-pretreated mice resulted in a markedly lower level of [Ca2+]i than that in endotoxin-treated mice. In the mice pretreated with TJ-9, the CA(2+)-ATPase activity in liver plasma membrane 18 h after endotoxin injection was markedly increased as compared to that in the endotoxin-treated mice. By contrast, the Ca(2+)-ATPase activity in liver mitochondria was lower in endotoxemic mice pretreated with TJ-9 than in mice given endotoxin alone. State 3 respiration and the respiratory control index (RCI), which are the parameters of mitochondrial function, were 41% and 35% lower, respectively, in the liver of mice given endotoxin than those levels in the control. However, the levels of state 3 and RCI in endotoxin-TJ-9-treated mice were markedly increased as compared to those of the endotoxin-treated mice. These findings suggest the protective effect of TJ-9 in the damage of liver mitochondrial function in endotoxin-poisoned mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A case of renal pseudotumor caused by pyelonephritis].

A case of renal pseudotumor due to pyelonephritis is reported. A 70-year-old female was admitted to our hospital for the evaluation of right renal mass in pyelogram. She had had episodes of pyelonephritis many times. Computed tomography (CT) revealed poorly marginated low density mass that exhibits inhomogenous enhancement with contrast medium. Angiography showed an avascular mass. On magnetic resonance imaging (MRI), the mass was isointensity or slightly low intensity on T1 weighted scan, while it showed low intensity on T2 weighted scan. The patient died from small cell carcinoma in the lung two years later. Autopsy was performed and no malignancy was found in the kidney. MRI was useful to differentiate such inflammatory change from renal tumor, which is mostly high intensity on T2 weighted scan.

Aged↗

[CO2US via an implantable port--drug distribution in intraarterial chemotherapy for hepatic tumors and evaluation of effect].

The distribution of blood flow was determined from the distribution of CO2 by US performed during the infusion of CO2 microbubbles via an implantable port (IP-CO2US) in intraarterial chemotherapy for hepatic tumor, and the usefulness of this method in determining tumor vascularity and evaluating the effects of therapy was investigated. A total of 16 patients, 12 of whom had metastatic liver tumor, two hepatocellular carcinoma, one gall bladder carcinoma, and one cholangiocellular carcinoma were studied. The enhanced areas in the liver in 16 patients in whom IP-CO2US was performed a total of 24 times were consistent in all cases with the enhanced areas demonstrated by IP-RI angiography performed a total of 10 times within 10 days, and were also consistent with one exception with the enhanced areas demonstrated by IP-CTA performed 14 times. The tumor detection rate was markedly higher with IP-CO2US than with plain US or IP-DSA, and was similar to that of IP-CTA. Evaluation of the vascularity of individual nodules by IP-CO2US surpassed that by IP-DSA, and was similar to that of IP-CTA. It was demonstrated that blood flow distribution (intrahepatic drug distribution) can be equally well grasped with IP-CO2US, which is a simple and convenient method, as with IP-RI angiography. It was also suggested that IP-CO2US is useful in the evaluation of tumor vascularity and the effect of therapy.

Antineoplastic Agents↗

The coexistence of abdominal aortic aneurysm and early gastric cancer: report of three cases.

The surgical approach for patients with abdominal aortic aneurysm (AAA) and coexistent abdominal malignancy remains controversial. We report herein three cases of coincident AAA and early gastric cancer, all of whom were treated by a two-stage operation and underwent curative surgery for their gastric cancer. The principles of our surgical approach are as follows: (1) the lesion which requires urgent surgery should be operated on first, and if both lesions show absolute indications, a one-stage surgical procedure should then be performed; (2) a two-stage surgical procedure in which aneurysmectomy is performed first should be undertaken when no absolute indications for urgent surgery exist for either lesion; (3) a one-stage surgical procedure should only be performed when surgery on one lesion makes the other lesion highly dangerous; and (4) in patients with a poor prognosis because of far advanced cancer in whom the AAA shows no sign of rupturing, only a gastrectomy should be performed.

Aged↗

Distribution of radioisotopic beryllium in mice after administration by various routes of injection.

A 7BeCl2 solution containing 0.5 micrograms Be per mouse was injected subcutaneously, intraperitoneally, intramuscularly, intrathoracically, and intravenously, and distribution was observed for periods up to 1 wk. 7Be was excreted more rapidly following intravenous injection than by the other routes of injection. The amount of Be found in the liver or the spleen was substantial at 1 d after intraperitoneal injection. It increased more in the spleen at 7 d after either intraperitoneal or intrathoracic injection. On the other hand, the amounts of Be stayed almost constant in the kidneys, by the various routes of injection. When injected intrathoracically, the amounts of Be in the heart and the lung were greater than when administered by the other routes of injection. The amounts of Be in the femurs of mice administered by these routes of injection, except with intravenous injection, were greater than in the other organs. The percentage of 7Be in the mineralized bone was 90% of that of 7Be in the femurs when injected intraperitoneally or intrathoracically. However, the ratio of Be in the mineralized bone to that in the bone marrow was 3 to 2. Beryllium had thus a closer affinity for the femurs than for the other organs investigated, with the different modes of administration used. The amount of Be in the entire skeleton was estimated to be substantial. Within the limitations of 1 wk of exposure, the skeleton would appear to be a critical organ. This would suggest that osteosarcomas may occur following administration of Be to laboratory animals for a long-term period.

Animals↗

Kinetics of infectivity are dissociated from PrP accumulation in salivary glands of Creutzfeldt-Jakob disease agent-inoculated mice.

The protease-resistant isoform of prion protein (PrP) has been implicated in the pathogenesis and transmission of Creutzfeldt-Jakob disease (CJD), scrapie and other related diseases, but the relationship between the infectious agent and PrP awaits elucidation. In the present study, we have examined levels of infectivity together with accumulation of the protease-resistant form of PrP (PrPCJD) in various tissues of CJD agent-inoculated mice. Accumulation of PrPCJD occurred only in tissues, including brain, salivary gland and spleen, in which infectivity was readily detectable throughout the course of the experiment. The brain showed the highest levels of both infectivity and PrPCJD accumulation, with well correlated kinetics. On the other hand, the high titres of infectivity detected in salivary gland and spleen early after inoculation of the agent were obviously distinguishable from PrPCJD. Furthermore, in the salivary gland, the kinetics of infectivity and the accumulation of PrPCJD reversed; infectivity declined as PrPCJD accumulated in the tissue. Our findings indicate that PrPCJD accumulation is associated with replication of the agent; however, PrPCJD is unlikely to be the agent itself.

Animals↗

[Biological characters of the clinically isolated strains of Escherichia coli O157:H7 in Canada].

Biological characters of enterohemorrhagic Escherichia coli (EHEC) strains isolated from food poisoning cases in Canada, 1987-1988 were examined in comparison with that isolated in Saitama, 1990. The Saitama strain was found to belong to biotype I, and biotypes I and II were found in Canada. Most of the strains including the Saitama strain were found to have siderophilins suggesting their advantageous growth in vivo. An enteroinvasive strain with 140 megadalton (Md) plasmid and two colicinogenic strains with 4.8 Md plasmids were detected. All strains were found to have 60 Md plasmids. This plasmid might be specific for this serotype. A few strains were resistant to streptomycin (SM) and/or tetracycline (TC), and a strain transferred its SM-TC resistances by conjugation. Many strains including the Saitama strain were found to produce vero cytotoxin (VT) types 1 and 2 (VT1 and VT2). A few type 2 and untypable toxin producing strains were also detected. VT titers produced by untypable toxin producing strains were over 10 times lower than those by other strains. High annealing temperature for PCR amplification of VT1 gene and a variety of annealing temperatures of VT2 gene suggested that the nucleotide sequences for VT1 gene were well preserved, but that those for VT2 might have some mutations.

Animals↗

Preventive effects of a traditional Chinese medicine (sho-saiko-to) against oxygen toxicity and membrane damage during endotoxemia.

The preventive effects of a traditional Chinese medicine Sho-saiko-to (Kampo prescription, TJ-9) were determined from oxygen toxicity and membrane damage in liver during endotoxemia. The liver lipid peroxide level and xanthine oxidase activity 18 h after administration of endotoxin (6 mg/kg, i.p.) to TJ-9 (500 mg/kg/d, p.o.)-pretreated mice were markedly lower than that in endotoxin-treated mice, whereas the administration of TJ-9 significantly increased superoxide dismutase and glutathione peroxide activities in liver of endotoxin-injected mice. In the mice pretreated with a TJ-9, the levels of alpha-tocopherol and nonprotein SH in liver tissue 18 h after endotoxin injection were markedly increased as compared to those in endotoxin-treated mice. Leakages of acid phosphatase and lactate dehydrogenase isozyme in serum were markedly lower in endotoxin-TJ-9-treated mice than those in mice given endotoxin. The administration of TJ-9 clearly prevented the membrane protein damage arising from endotoxin challenge. Kampo prescription Sho-saiko-to thus appears to protect the liver plasma membrane from injury by free radicals which occur in a tissue ischemic state during endotoxemia.

Acid Phosphatase↗

Decline in plasma membrane Ca(2+)-ATPase activity and increase in cytosolic-free Ca2+ concentration of endotoxin-injected mice livers.

The present study describes the activity of Ca(2+)-ATPase in liver plasma membrane and cytosolic-free Ca2+ concentration ([Ca2+]i) in an individual vital cell in mouse liver 18 h after endotoxin administration. Ca(2+)-ATPase activity in liver plasma membrane in the poisoned mice was markedly decreased to 28% of that in the control. The membrane protein damage in liver was found mostly in the molecular weight (M.W.) regions near 60,000-150,000 in endotoxemic mice, and was markedly injured near 140,000 (M. W. of Ca(2+)-ATPase in liver plasma membrane). The level of [Ca2+]i in liver cells in endotoxin-poisoned mice was greater at 18 h postintoxication than that of the control. These findings suggest the possibility that the depression of Ca(2+)-ATPase activity in liver plasma membrane in mice may contribute to membrane damage caused by the endotoxin, and that the increase of [Ca2+]i in liver cytoplasm may partially explain various endotoxin-induced metabolic disorders.

Animals↗

Venous surgery in resection for abdominal malignancy.

Vascular surgical techniques were applied to the radical resection of carcinoma of the liver, biliary tract and pancreas. Distal and proximal portal vein reconstruction, respectively, was carried out in 16 patients with carcinoma of the pancreas and 16 with cancer of the liver and biliary tract. Hepatic vein trunks with tumour involvement were resected and reconstructed by various techniques in six patients. A suprarenal segment of the inferior vena cava was completely replaced by a prosthetic graft in three patients with retroperitoneal malignancy. Venous surgery increased the resectability of malignant tumours and preserved circulation in the organ remnant, although the long-term effect on survival is not yet clear. Vascular surgical techniques should be applied more widely in the field of general abdominal surgery.

Abdominal Neoplasms↗

[Congenital arteriovenous malformation of the kidney: report of two cases--detection by digital subtraction angiography with carbon dioxide].

Two cases of arteriovenous malformation of the kidney were reported. The first case was a 19-year-old female, complaining of right flank pain and gross hematuria. Right selective renal arteriography revealed a 2 x 1.5 cm large cisoid type arteriovenous malformation at the most distal region of the lower branch of the renal artery. Transcatheter embolization, using Gelfoam and absolute ethanol, was successfully done, which was confirmed with repeated digital subtraction angiography with carbon dioxide (CO2-DSA). The second patient was a 55-year-old female with past history of right idiopathic renal bleeding, complaining of right flank colicky pain and gross hematuria. Right selective renal arteriography was done without any pathological findings, while CO2-DSA documented an arteriovenous malformation in the hilar region. Transcatheter embolization was not done, because the malformation seemed to be proximally located. Thus CO2-DSA was thought to be a reliable method in the diagnosis of arteriovenous fistula.

Adult↗

Significance of hepatic vein reconstruction in hepatectomy.

BACKGROUND: To preserve remnant liver function, hepatectomy combined with hepatic vein (HV) reconstruction was performed in resection of the tumor located at the confluence of the HV and inferior vena cava. METHODS: Eight patients underwent HV reconstruction: the right HV in three, the middle HV in four, and the left HV in one. An external iliac vein graft was used in two patients, a superficial femoral vein graft in three, and a long saphenous vein graft in one. In one patient a patch graft was applied to the right HV; another patient underwent end-to-end anastomosis of the right HV without grafting. RESULTS: There were no operative deaths and liver function was adequate throughout the postoperative period. Complications included two cases of minor biliary fistula. The middle HV with a saphenous graft and the left HV with an external iliac graft became occluded because of size mismatch at the anastomosis. Six veins were patent at 1 month and three were still patent after 30 months. CONCLUSIONS: To prevent graft occlusion, it is important to select an autologous vein of optimal size and avoid inflammation of the liver stump. HV reconstruction appears to be a new surgical option for patients undergoing hepatectomy.

Adult↗

Serotonin as a factor involved in pathophysiology of thromboangiitis obliterans.

Whole blood and plasma levels of serotonin (5-hydroxy-tryptamine, 5-HT) as well as its uptake and spontaneous release from blood platelets were studied in 20 patients suffering from thromboangiitis obliterans (TAO, Buerger's disease) and 20 healthy subjects matched in pairs for age. Results of patients suffering from thromboangiitis obliterans differed in several ways from those of controls. Whole blood 5-HT content was significantly lower in the group of patients compared to that of the control group. It was established that patients with Buerger's disease have significantly greater plasma concentrations of free serotonin. In Buerger's disease patients, maximal platelet serotonin uptake velocity (Vmax) was significantly decreased. It was associated with the enhanced spontaneous release of 5-HT from blood platelets. We conclude that impaired platelet serotonin uptake and increased local concentration of serotonin in the vicinity of platelets in Buerger's disease may lead to platelet activation via 5-HT2 receptors, and it could be involved in the pathogenesis of thromboembolic complications.

Adult↗

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↗

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↗

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↗