Search PubMed⌕ Search

Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 199 records · Page 11Linked to original sources

Distinct characters of Clostridium botulinum type A strains and their toxin associated with infant botulism in Japan.

Four strains of Clostridium botulinum type A having been associated with infant botulism in Japan, and another strain isolated from honey not associated with infant botulism, were found to be hemagglutinin (HA) negative. These strains do not produce L (Mr 500 kDa) nor LL toxin (Mr 900 kDa) but M toxin (Mr 300 kDa) only. No marked difference was found between the HA-positive and HA-negative strains in other biochemical properties, but the HA-negative strains tended to colonize more easily in the intestines of infant mice than did HA-positive strains. The toxin of HA-positive strains and that of HA-negative strains differed in the antigenicity of part of the toxic component and that of the nontoxic component, and in the molecular size of the toxic component.

Botulinum Toxins↗

Participation of calcium ion on depletion mechanism of liver glycogen by purified glucocorticoid antagonizing factor released in blood during endotoxemia.

The present study was conducted by the use of purified glucocorticoid antagonizing factor (GAF) released in blood of endotoxemic mice to determine whether or not the factor (GAF and Ca2+) may play a possible role of mediator in depletion mechanism of liver glycogen in endotoxemia. The liver glycogen level in 2 hr after injection with GAF plus cortisone-treated mice was markedly lower than that in cortisone alone-treated mice. However, the administration of trifluoperazine or verapamil markedly increased glycogen levels in liver of GAF plus cortisone-injected mice. On the other hand, when the mice fed a calcium-free diet were injected with GAF plus cortisone, there was merely a significant difference in liver glycogen level as compared to cortisone alone-treated mice. The level of Ca2+ in liver cytosol fraction in cortisone-treated mice was higher 2 hr after GAF injection than that in the cortisone alone-treated one. The phosphorylase a activity in liver 2 hr after injection of GAF plus cortisone did not show a significant difference as compared to that in mice treated with cortisone alone. However, the activity ratio of glycogen synthase enzyme (synthase I synthase I + D) was decreased in GAF plus cortisone-treated mice as compared to that in cortisone alone-treated mice. These findings suggest that there are participations of Ca2+ and mediator GAF released from reticuloendothelial system (RES macrophages in glucoregulation of endotoxemia. Thus, it may be speculated that intracellular Ca2+ may mediate glycogenesis rather than glycogenolysis in the depletion mechanism of liver glycogen during GAF-poisoning.

Animals↗

Iliac artery stenosis and occlusion: preliminary results of treatment with Gianturco expandable metallic stents.

Ten patients with atherosclerotic stenosis or occlusion of the iliac artery were treated with Gianturco expandable metallic stents. In the five cases of stenosis, only balloon dilation was performed prior to placement of stents. The five patients with occluded arteries were given intraarterial infusions of urokinase before balloon dilation and stent placement. Clinical symptoms improved in all patients, and no technical failures or complications occurred. Doppler ankle-brachial index studies were performed in nine cases, and in all nine cases the indexes improved after stent placement. During follow-up of 2-18 months (mean, 10.3 months), all arteries remained patent. Follow-up angiograms showed slight intimal thickening and no restenosis. Long-term follow-up and more clinical experience will be necessary to evaluate the efficacy of this stent. However, preliminary results suggest that the Gianturco expandable metallic stent is of value in the treatment of arterial occlusive disease.

Adult↗

Comparative studies on Clostridium botulinum type A strains associated with infant botulism in Japan and in California, USA.

Twenty strains of Clostridium botulinum type A associated with infant botulism cases, six in Japan and 14 in California, USA, were compared in their characters. All six Japanese strains produced medium-sized progenitor toxin (M toxin; Mr 300 k) but no hemagglutinin and showed lower 50% infective doses (ID50) in the infant mouse test; whereas most American strains produced large-sized progenitor toxin (L + LL toxins; Mr 500 k and 900 k) and hemagglutinin in addition to M toxin and showed higher ID50 in infant mice. No marked difference in the biochemical properties was found between the two groups except for two American strains.

Animals↗

On the changes in peripheral red cells in mice exposed to vinyl chloride monomer.

The diseases known as the Vinyl Chloride Monomer (VCM) Syndrome include hepatic angiosarcoma, acroosteolysis and Raynaud's phenomenon. These, however, are known to be clinically recognizable from several to over 10 years after the actual exposure to VCM. By fluorescence microscopy the authors examined smeared samples of peripheral blood obtained from vinyl chloride workers, and observed the existence of basophilic stippled erythrocytes (BSE). In this paper, we report the changes of peripheral red cells during VCM exposure tests on mice. These changes in the peripheral blood could be observed as early as 24 hours after the start of the VCM exposure at higher concentrations, and in 72 hours even at comparatively lower VCM levels of 30 to 40 ppm. The tests have also confirmed that the rate of emergence of BSE differs according to the level of VCM and to the duration of VCM exposure.

Animals↗

Organ-specific autoimmune disease induced in mice by elimination of T cell subsets. V. Neonatal administration of cyclosporin A causes autoimmune disease.

Cyclosporin A (CsA), a potent immunosuppressive drug, caused organ-specific autoimmune disease, such as gastritis with anti-parietal cell autoantibodies or oophoritis with anti-oocyte autoantibodies, in BALB/c mice when the drug was administered daily for 1 wk to newborns. Administration to adult mice did not. CsA abrogated the production of L3T4+ T cells and Lyt-2+ T cells in the thymus. Consequently, these T cells were substantially depleted from the peripheral lymphoid organs, especially when the drug was administered from the day of birth. Autoimmune disease was prevented when CsA-treated newborn mice were inoculated with splenic T cells from normal syngeneic mice. However, removal of the thymus immediately after neonatal CsA treatment produced 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 was accompanied by the development of circulating autoantibodies specific for the corresponding organ Ag. Immunopathology of these autoimmune diseases was quite similar to that of human organ-specific autoimmune diseases.

Animals↗

Microvascular anastomosis using a new diode laser system with a contact probe.

The aim of the present study was to demonstrate the usefulness of our newly produced diode laser device (an 830-nm output of 190 mW CW) for microvascular end-to-end anastomoses. In the device, diode laser energy is delivered to a contact ceramic tip with a 200-microns diameter output end. Its wavelength is 830 nm and its power 60 mW. This device is small (30 x 25 x 10 cm), lightweight (gross weight 3kg), and easy to manipulate. Compared with conventional microvascular suture anastomosis (CMSA), the time required for the laser-assisted vascular anastomoses (LAVA) was reduced by almost half. Anastomosed portions of both methods were examined 1, 2, 4, 12, and 24 weeks later for patency and aneurysm formation. The patency rate and incidence of aneurysmal formation were the same in both groups. Histological examination revealed that LAVA is superior to CMSA in the smoothness of the inner surface, less inflammatory reaction, and normal collagen and elastic reorientation. The tensile strength and bursting pressure measured immediately after anastomosis demonstrated no significant difference between the two groups. It was concluded that this diode laser contact method may be clinically useful for microvascular surgery.

Anastomosis, Surgical↗

New method of photosensitizer accumulation for photodynamic therapy in an experimental liver tumor.

A new sensitizing method of photodynamic therapy for malignant tumors and its effects was studied. Prepared for the study were pheophorbide a (Phd), dissolved in an oily contrast medium, Lipiodol (LPD-Phd), and water-soluble pheophorbide a (W-S Phd) as sensitizers, and VX-2 tumor in rabbit livers. The Phd distribution was compared after intraarterial (i.a.) administration of LPD-Phd or W-S Phd and intravenous (i.v.) administration of W-S Phd. Phd was extracted with methanol at 24 h after injection, and the supernatant absorbance was measured at 670 nm by spectrophotometry. The tumor showed higher values of Phd than did the liver with LPD-Phd i.a. and W-S Phd i.a. (P less than .01). Conversely, the tumor accumulated less Phd than did the liver with W-S Phd i.v. (P less than .05). We subsequently produced severe photo-destruction in a Walker tumor in a Sprague-Dawley rat liver with slight damage to adjacent liver tissue using LPD-Phd i.a. and Nd-YAG dye laser irradiation at 670 nm. The intraarterial administration of a photosensitizer may make it possible to treat liver tumors by photodynamic therapy.

Animals↗

Detection of pulmonary telangiectasia using dynamic pulmonary perfusion imaging in patients with liver cirrhosis.

Two cases of liver cirrhosis associated with marked hypoxemia are presented. Chest radiographs and cardiopulmonary function showed no abnormalities, except for the low diffusion capacity of carbon monoxide and slight elevation of the shunt ratio (20 and 6.2%, respectively), as estimated under conditions of 100% oxygen inhalation. Pulmonary perfusion imaging with Tc-99m macroaggregated albumin (MAA) revealed a significant radioisotope uptake in the lungs, brain, spleen, and both kidneys. Shunt ratios, estimated by the quantitative radionuclide method, were 60 and 68%, respectively. Dynamic pulmonary perfusion imaging revealed a gradual reduction in uptake in all areas of both lungs. The discrepancy of the shunt ratio between the two methods results from an abnormal dilatation of alveolar capillaries. The gradual reduction of radioactivity in areas of the lungs is caused by the passage of MAA particles through widened pulmonary capillaries.

Female↗

Reversibility of pulmonary telangiectasia in liver cirrhosis evidenced by serial dynamic pulmonary perfusion imaging.

Pulmonary perfusion imaging with Tc-99m MAA revealed significant uptake in the lungs, brain, spleen, and both kidneys of a 48-year-old woman with liver cirrhosis and pulmonary telangiectasia associated with marked hypoxemia and cyanosis. Dynamic pulmonary perfusion imaging revealed a gradual reduction after peak uptake in both lungs. Several weeks after albumin replacement, the hypoxia and dyspnea disappeared with no change in hepatocellular function. At that time, dynamic pulmonary perfusion imaging revealed a plateau-like time-activity curve of uptake in the lungs, as compared with the findings obtained during the state of severe hypoxemia. These observations suggest that pulmonary telangiectasia in a patient with liver cirrhosis may be due to functional vasodilatation. Serial dynamic pulmonary perfusion imaging indicates the passage of the MAA particles through the widened lumen of the pulmonary alveolar capillaries.

Female↗

Effect of calcium ion on lipid peroxide formation in endotoxemic mice.

The present study was conducted to determine the possible role of intracellular Ca2+ in lipid peroxide formation in endotoxin-poisoned mice. Leakages of LDH isozyme and acid phosphatase in serum of mice fed a Ca2+-deficient diet were remarkably increased after administration of 200 micrograms of endotoxin compared to that in endotoxin-nontreated Ca2+-deficient mice. Superoxide anion generation in liver of Ca2+-deficient mice and in mice fed a normal diet greatly increased after endotoxin administration. On the contrary, after endotoxin injection there was scarcely any difference in SOD activity of liver of Ca2+-deficient mice as compared to that in endotoxin-nontreated Ca2+-deficient mice. In spite of an increase of superoxide anion generation there was little or no effect of endotoxin administration on lipid peroxide formation in mice given a Ca2+-deficient diet. In the mice treated with a Ca2+-deficient diet, free radical scavenger levels (alpha-tocopherol and nonprotein sulfhydryl) in liver tissue after endotoxin injection were markedly decreased compared to those in Ca2+-deficient diet alone. Mice fed a normal diet exhibited a significant decrease of lipid peroxide level in liver by injection of endotoxin together with verapamil (10 mg/kg, s.c.). When mice fed a normal diet were injected with endotoxin, the state 3 respiratory activity showed a 49% decrease, and respiratory control ratio (RCR) of endotoxemic mice liver mitochondria was 38% lower than normal liver mitochondria. No difference could be observed in levels of state 3 and RCR between the mice given verapamil plus endotoxin and the normal mice. These findings suggest the possibility that Ca2+ may participate in the free radical formation in the liver during endotoxemia and also that Ca2+ may play an important role in the damage of liver mitochondrial function in endotoxemic mice.

Animals↗

Measurement of urinary trypsin inhibitor in urine, plasma and cancer tissues of patients with stomach cancer.

Antiserum was obtained from rabbits immunized with a highly purified preparation of urinary trypsin inhibitor (UTI) conjugated with rabbit serum albumin. Anti-UTI antibody did not cross-react with antibody against inter-alpha-trypsin inhibitor (I alpha I) as determined by immunodiffusion against human plasma. A highly sensitive enzyme immunoassay was developed for the determination of UTI-related antigens (UTIR) in plasma, urine and cancer tissues. The level of UTIR correlated with UTI activity in urine. UTIR levels in urine and plasma did not change with age, but UTIR levels were higher in the stomach cancer tissue than in the surrounding stomach mucosa. UTIR levels did not correlate with I alpha I levels in the plasma of patients with stomach cancer, thus the increase was not considered due to the contamination of circulating I alpha I in the cancer tissues.

Adolescent↗

Hydroxylapatite for laryngotracheal framework reconstruction.

Hydroxylapatite plates and rings were employed for reconstruction of the laryngotracheal framework in 12 patients. The cause of the framework defect was surgery for stenosis in nine cases and removal of malignancy in the other three. The trough method associated with a two-stage procedure was tolerated in all 12 cases. Hydroxylapatite plates or rings were used to reconstruct the framework during the second stage. The implant was well taken in all cases, without any infection or rejection. Nine of the 12 cases resulted in excellent airways.

Adult↗

The sennoside constituents of rhei rhizoma and sennae folium as inhibitors of serum monoamine oxidase.

Four (in total) compounds with inhibitory effects on the activity of bovine serum monoamine oxidase were isolated from the methanol-water extracts of Rhei Rhizoma (Daiou) and Sennae Folium (Senna), and identified as sennosides A, B, E and F. Among them, sennosides A and B were obtained from both Rhei Rhizoma and Sennae Folium, while sennosides E and F were detected only in the former. The 50% inhibitory concentrations of the four sennosides were 17, 9, 24 and 13 microM, respectively, and the type of inhibition by seenosides A and B with respect to allylamine as the substrate was non-competitive.

Anthraquinones↗

[Importance of the conjugated antibody for the induction of selective effect of adriamycin conjugated with anti AFP monoclonal antibody and entrapped in liposomes against AFP producing tumors].

We investigated experimentally the effect of adriamycin (ADM) conjugated with anti alpha-fetoprotein (AFP) monoclonal antibodies and entrapped in liposomes (Lip-ADM = AbAFP) in vitro or in vivo. In the present study, we examined the importance of the conjugated antibody for the induction of selective therapeutic effect of Lip-ADM = AbAFP against AFP producing tumors. As the target tumors, AFP producing human hepatoma strain, Li-7, and AFP non-producing human breast cancer strain, MX-1 maintained in BALB/c nu/nu male mice were used. In order to evaluate the importance of the conjugated antibody, we prepared also ADM conjugated with normal mouse IgG, and entrapped in liposomes Lip-ADM = NIgG, of which therapeutic effects were compared with that of Lip-ADM = AbAFP. Judging from the tumor growth curve and the tumor weight, the therapeutic effect of Lip-ADM = AbAFP was greater against Li-7 than that of Lip-ADM = NIgG. On the other hand, both conjugates showed similar effects against MX-1. As the results it is suggested that the antibody which recognizes the antigen expressed on the target tumor cells can solely increase the therapeutic effect of ADM entrapped in liposomes (Lip-ADM) and that the main factors which contribute to the efficient therapeutic effect of the conjugate were the sensitibility to ADM, the affinity of the tumor cells to liposomes and the superiority of the conjugated antibody.

Animals↗

[Blood flow disturbance in digestive organs--a viewpoint of vascular surgery].

Various blood flow disturbances in intraabdominal digestive organs were studied clinically and experimentally from a viewpoint of vascular surgery. Acute gastric mucosal lesion may occur due to ischemia and reperfusion injury of the gastric mucosa. Bleeding from stomach ulcer may be rarely caused by consumption coagulopathy along with aortic aneurysm. Heparin therapy was successful to interrupt it. Gastrectomy is not indicated for such condition but aneurysm should be repaired. Portal vein reconstruction for the radical resection of hepatic, biliary and pancreatic cancers should be carefully made, because early or late stenosis occurs frequently, and they may connect to early or late morbidities or mortalities. On the other hand, resection and replacement of the suprarenal vena cava invaded by the retroperitoneal malignant tumor may be safely carried out. For the acute mesenteric arterial occlusion, early diagnosis and arterial reconstruction are essential to save catastrophe. Positive Doppler sound on the vasa recta seems to be the most reliable parameter for assessing bowel viability. Approach from the proximal large arteries is recommended for uncontrollable intraperitoneal bleeding.

Digestive System Neoplasms↗

Aggressive surgery for carcinoma of the gallbladder.

Forty patients with gallbladder cancer were admitted to our institution in a 9-year period. For two patients with Nevin's stage I carcinoma who had undergone cholecystectomy, resection of the lower portion of the fourth and fifth segments of the liver and extrahepatic bile duct with dissection of lymph nodes was carried out as a second-stage operation. Thirteen patients with stage V carcinoma underwent extensive aggressive operations. Operative procedures comprised various types of liver resection with cholecystectomy and extrahepatic bile duct resection and wide lymph node dissection in all cases, portal vein reconstruction in 3, pancreatoduodenectomy in 3, partial colectomy in 3, and right nephrectomy in 1. The operative and in-hospital mortality rates were 0%. Two patients with stage I carcinoma are both doing well. Two patients with stage V carcinoma who underwent an extended operation are working without recurrence 7 years 8 months and 8 years 5 months after surgery. From our experiences we believe that long-term survival may be achieved by aggressive surgery if it is suitably indicated.

Adult↗