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Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 217 records · Page 12Linked to original sources

[Antitumor effect of IL-2 entrapped in liposomes on rat hepatoma, AH-66].

The human recombinant interleukin 2 (IL-2) was entrapped in liposomes, and the therapeutic effects of the liposomes containing IL-2 (Lip-IL-2) were experimentally studied using the rat hepatoma strain, AH-66, maintained in donryu rats and challenged subcutaneously in the inguinal region. The peri-tumor injections of Lip-IL-2 (15 X 10(4)/kg units for the IL-2 dose) significantly inhibited the tumor growth as determined from the relative mean tumor weight, although no therapeutic effects were observed when the unentrapped IL-2 or liposomes containing saline was administered rats in the same way as the injections of Lip-IL-2. They also prolonged the survival time of rats. The studies of serum IL-2 values after i.v. or s.c. injections of Lip-IL-2 revealed that IL-2 was released gradually from the liposomes containing IL-2 into the circulation. As the result of the tumor tissue staining of the immunoperoxidase 18 hrs after the peri-tumor injection of IL-2, it was shown that a number of macrophages infiltrated into the tumor tissue and degenerated tumor cells were observed adjacent to those macrophages. It is suggested that Lip-IL-2 is useful as an antineoplastic agent in the immunotherapy and that the therapeutic effects of Lip-IL-2 would be related to both the slow release of IL-2 and the cytotoxicity on the tumor cells mediated by the macrophages.

Animals↗

[Hemorrhagic gastric ulcer associated with consumption coagulopathy in the dissecting aortic aneurysm--a case report].

A case of the hemorrhagic gastric ulcer and post-operative stomal ulcer associated with the consumption coagulopathy in the dissecting aortic aneurysm is presented. A 68 year old man, who had diagnosed as having the dissecting aortic aneurysm (DeBakey III) in 1985 and had been attending to our hospital as an outpatient since then, was admitted to our hospital because of the hemorrhagic gastric ulcer on July 3rd, 1987. Although the wide resection of stomach was performed after the admission, the hemorrhagic stomal ulcer was developed 4 weeks after the operation. The administration of heparin in addition to antacids to improve the consumption coagulopathy, having been caused by thrombus formation in the aneurysm, was effective in control of the hemorrhage and also making the stomal ulcer scarred. It is suggested that ischemia of the stomach mucosa, which seemed to have been induced by the dissecting aortic aneurysm, was responsible for the development of the ulcers in this case and the hemorrhage from them was caused mainly by the consumption coagulopathy derived from thrombus formation in the aneurysm.

Aged↗

The urokinase type of plasminogen activator in cancer of digestive tracts.

The amounts of urokinase (UK) antigen and tissue plasminogen activator (t-PA) antigen were determined in plasma, urine and tissues of patients with cancer of digestive tracts. Urinary levels of UK, but not those of t-PA increased in patients with cancer, and generally decreased after the removal of cancer by operation. Urinary UK levels kept increasing in patients with recurrence of cancer or with metastasis into liver or peritoneum. Plasma levels of t-PA, but not those of UK decreased in patients with cancer. When the amounts of UK were compared in cancer tissues and their adjacent normal mucosal layer, cancer tissues always had higher levels of UK, but t-PA levels were same between tumor tissues and normal mucosa. The results suggest that the type of plasminogen activator was UK-type in cancer of digestive tracts.

Adenocarcinoma↗

Thymus and autoimmunity. Transplantation of the thymus from cyclosporin A-treated mice causes organ-specific autoimmune disease in athymic nude mice.

Organ-specific autoimmune diseases such as gastritis, oophoritis, thyroiditis, or insulitis developed in athymic nu/nu mice after engraftment of the thymus from euthymic nu/+ mice treated with cyclosporin A (CsA), a potent immuno-suppressant. The development of autoimmune disease in the nu/nu mice was prevented by inoculation of thymocyte suspensions prepared from normal nu/+ mice, but not by thymocyte suspensions from CsA-treated nu/+ mice. Cotransplantation of normal nu/+ mouse thymus with CsA-treated thymus also suppressed the development of autoimmune disease. Inoculation of spleen cell suspensions prepared from normal adult nu/+ mice prevented autoimmune disease, but inoculation of those from newborn nu/+ mice did not. Thus, CsA appears to interfere selectively with the thymic production of certain suppressor T cells controlling self-reactive (autoimmune) T cells, allowing the latter to expand and cause autoimmune disease.

Animals↗

Immunologic and clinical studies on murine experimental autoimmune gastritis induced by neonatal thymectomy.

Experimental autoimmune gastritis (AIG), defined by the appearance of auto antibodies to parietal cells, was induced by neonatal thymectomy in BALB/c nu/+mice 3 days after birth. Vitamin B12 absorption and intrinsic factor in the stomach extract decreased compared with those in AIG-negative control groups. No decrease of the serum A/G ratio in AIG-bearing mice was observed. Although development of anemia, as evaluated by a decrease in hematocrit value, was poor until 12 mo of age and the gastric mucosa was hypertrophic, the AIG resembled human pernicious anemia rather than Ménétrier's disease. Adoptive transfer of spleen cells, but not sera, of AIG-bearing nu/+ into BALB/c nu/nu mice caused AIG in all animals 1 mo later, indicating the involvement of lymphocytes in the induction mechanism of AIG. Cytofluorometric and immunohistochemical analysis of lymphocytes in the gastric mucosa revealed T-cell infiltration at an early stage (1.5-3 mo) followed by B cell infiltration (6 mo). When the fraction enriched with parietal cells, which were intensively stained with sera of AIG-bearing mice and fluorescent antibody to mouse immunoglobulin G, was injected into the foot pads of AIG-bearing nude mice, typical delayed-type hypersensitivity reaction was observed in all animals. This was not seen in the mice injected with the cell fraction enriched with chief cells, although a few of them were stained by the immunofluorescent technique. Thus, the delayed-type hypersensitivity reaction seems to be directly involved in the mechanism of tissue damage.

Anemia, Pernicious↗

Purification of Clostridium botulinum type G progenitor toxin.

Clostridium botulinum type G cultured for 6 days at 30 degrees C in proteose peptone-yeast extract-glucose medium produced toxin of 1.3 x 10(4) LD50/ml. The toxin was precipitated at pH 4.0, extracted with 0.2 M phosphate buffer, pH 6.0, and activated with trypsin. Sonic treatment and trypsinization of the residual precipitate released additional toxin, the toxicity of which corresponded to that detected in whole culture. Activated toxin obtained from the first extract and that from the residual precipitate were combined and purified by salting out, acid precipitation, gel filtration on Sephadex G-200, chromatography on SP-Sephadex, and a second gel filtration on Sephadex G-200. The yield of purified toxin from 10 liters of culture was 22.9 mg an 1.1 X 10(8) mouse ip LD50 with a specific toxicity of 3.0 X 10(7) mouse ip LD50/mg nitrogen. The molecular weight of the toxin was about 500,000, corresponding to that of L toxin of the other types. No M nor LL toxin was detected.

Botulinum Toxins↗

Positive reaction in mouse ligated intestinal loop assay with nonenterotoxigenic and nonhemolytic strains of Staphylococcus aureus.

Nonenterotoxigenic and nonhemolytic strains of Staphylococcus aureus exhibited a positive reaction in the mouse intestinal loop assay except for a strain negative for the egg yolk reaction. Edema and swelling in all positive loops, increased bacterial cell numbers within intestinal loops, and extremely close adhesion to or inclusion of numerous bacterial cells in HeLa cells after inoculation of the strains were observed. These results suggest a possible invasive ability of the strains.

Animals↗

[A case report of hemosuccus pancreaticus caused by a ruptured splenic aneurysm].

A 65-year-old female with hematemesis due to hemosuccus pancreaticus observed by endoscopy was reported. Selective angiography demonstrated 4 aneurysms of the splenic artery ramificated from the superior mesenteric artery (SMA). Of these 4 aneurysms, the largest one was located at 5mm distal from the SMA ruptured into the pancreatic duct. Resection of the splenic aneurysms, splenectomy and cholecystectomy for concomitant gallstone were successfully performed and the patient had no further gastrointestinal bleeding. True aneurysms with marked arteriosclerosis were confirmed histopathologically. Of 48 cases of hemosuccus pancreaticus reported in the literature, 15 cases caused by ruptured true aneurysms were reviewed. Pathogenesis, diagnosis and surgical procedure for this rare syndrome were discussed.

Aged↗

Effects of cadralazine on systemic blood pressure, renal function and plasma renin activity in anesthetized dogs.

Renal effects of ethyl 6-[ethyl(2-hydroxypropyl)amino]-3-pyridazinecarbazate (cadralazine), a newly synthesized vasodilator with a pyridazine ring, were studied in anesthetized dogs. 30 min after intravenous (i.v.) injection of cadralazine in a dose of 1 mg/kg diastolic blood pressure (DBP) decreased from the control value of 115 +/- 4 mmHg to 108 +/- 3 mmHg. The decrease continued, being accompanied by an increase in heart rate, throughout the experimental period of 5 h. Renal vascular resistance was decreased significantly, while glomerular filtration rate and urine volume remained unchanged. Urinary excretions of sodium and potassium were increased about 1.5 to 2 times as compared to pre-injection control values. Hypotension and natriuresis were followed by increased plasma renin activity in the artery or renal vein. On the other hand, i.v. injection of hydralazine (0.3 mg/kg) promptly decreased DBP and urinary sodium excretion, 15 min after administration, with blood pressure tending to revert to the control value. These results indicate that cadralazine has hypotensive and renal vasodilating actions, characterized by a slow onset and long duration, when compared with hydralazine.

Anesthesia↗

Selective stripping operation based on Doppler ultrasonic findings for primary varicose veins of the lower extremities.

In 337 limbs (208 patients) with primary varicose veins, Doppler ultrasound was used to detect reverse flow in the saphenous veins caused by manual compression of the calf. According to the extent of reverse flow in the saphenous trunks, varicosities of the long saphenous vein were classified into five types and the short saphenous vein, into four types. Two hundred five (66.3%) of 309 limbs with varicosities of the long saphenous vein had reverse flow in the entire saphenous trunk from the groin to the ankle. In varicosities of the short saphenous vein, 37 (52.9%) of 70 limbs showed reverse flow from the popliteal fossa to the ankle. The other limbs demonstrated reverse flow only in some segments of the saphenous veins. On the basis of these Doppler ultrasonic findings, selective stripping operations were performed on 80 limbs, in which only the segments with venous reverse flow were selectively removed. Postoperative plethysmographic measurement of the venous reflux volume and follow-up studies showed that results of the selective stripping operations were as satisfactory as those of the standard stripping operations (189 limbs) in which the entire saphenous vein was removed. Furthermore, the selective stripping operation was advantageous in reducing the incidence of nerve injury.

Blood Flow Velocity↗

[Repeated intra-abdominal administration of CDDP in carcinomatous peritonitis due to gastric cancer--a case report].

Two years and 10 months after gastrectomy, a 38-year-old man was diagnosed as having carcinomatous peritonitis due to gastric cancer. He was treated by intra-abdominal administration of 100 mg CDDP three times in addition to UFT. After each administration of CDDP, the amount of ascites and the serum value of CEA were decreased. Subjective symptoms, such as epigastric pain or sensation of fullness, were also improved. Although one year and 8 months has passed since the first administration of CDDP, the performance status of the patient remains 0. Nausea or vomiting was noted within 2 days after each administration. However, severe complications, like renal failure or intra-abdominal hemorrhage, were not observed. These findings suggest that repeated intra-abdominal administration of CDDP may be a useful therapy for carcinomatous peritonitis due to gastric cancer.

Adenocarcinoma↗

Hemodynamic effects of cadralazine in hexamethonium treated and non-treated anesthetized dogs.

Hemodynamic effects of the newly synthesized vasodilator cadralazine (ethyl(+/)-6-[ethyl(2-hydroxypropyl)amino]-3- pyridazinecarbazate) were compared with those of hydralazine and budralazine in hexamethonium treated and non-treated anesthetized dogs. In hexamethonium non-treated dogs, cadralazine (1 and 3 mg/kg i.v.) exerted a dose-dependent and sustained decrease in systolic and diastolic arterial blood pressure similar to that of budralazine (10 mg/kg i.v.) and the effect was slow in onset and long lasting until 5 h after administration compared with hydralazine (0.5 and 1 mg/kg i.v.). Total peripheral vascular resistance was decreased by these three drugs. The common carotid, femoral and renal arterial blood flow increased as a result of the decrease in vascular resistance, but the superior mesenteric arterial flow has not significantly changed. Blood flow increase in the renal artery was fast and that in the femoral artery was predominant. Treatment with hexamethonium decreased blood pressure, but cadralazine caused a further decrease within 60 min similarly to the decrease pattern of hydralazine. Common carotid and femoral arterial vascular resistance also decreased by hexamethonium treatment and a further decrease was observed by administration of cadralazine. Heart rate and cardiac output were immediately and significantly increased by cadralazine, but the increment in heart rate was diminished by the treatment with hexamethonium. Therefore the tachycardiac response is assumed to be caused by baroreceptor reflex and compensates the decrease in vascular resistance which results in moderation of manifestation of the early stage hypotensive effect of cadralazine.

Anesthesia↗

Purification and characteristics of glucocorticoid antagonizing factor in endotoxemia.

The present study involved the purification of GAF (glucocorticoid antagonizing factor) released in blood of endotoxemic mice, using the inhibition rate of tryptophan oxygenase (TO) activity in the mice liver as a parameter, to determine if this plays a role in metabolic disorders. GAF-rich serum in zymosan-primed and endotoxin-injected mice was subjected to chromatography on DEAE-Sepharose CL-6B, Blue Sepharose CL-6B and Sephadex G-200 superfine columns. Finally, GAF fractions were purified by chromatography on a DEAE-Sepharose CL-6B column. The purified GAF showed a single band in electrophoresis in sodium dodecyl sulfate (SDS) polyacrylamide gel. The molecular weight of GAF was estimated to be 90,000. The purified GAF was regarded as glycoprotein. No factor (100 micrograms) exhibited lethal action on mice. The activity of TO in cortisone treated mice after injection of purified GAF was markedly lower than that in cortisone alone treated mice. On the other hand, there were no differences in tyrosine aminotransferase activities between the GAF plus cortisone injected group and cortisone only treated group. The glucose level after injection of GAF in cortisone treated mice initially showed hyperglycemia, but declined toward hypoglycemia 2 hr after injection, and thereafter returned nearly to the normal range by 4 hr. The liver glycogen level in GAF plus cortisone-treated mice was markedly lower than that in cortisone-alone treated mice.

Animals↗

Cell-mediated immunity caused by beryllium compounds.

Cells of spleen and lymph nodes were obtained from mice subcutaneously injected with BeCl2 once a week over a 6-week period. These cells were washed twice in cold phosphate-buffered saline and suspended at a final concentration of 2 x 10(7) cells in 1 ml of buffer. Subsequently, 0.5 ml of the suspension was injected into normal mice intravenously (passive transfer). The findings of the experiments using these mice are summarized as follows: (1) The footpad reaction test was performed 24 hrs after passive transfer. The mice receiving spleen cells or lymph node cells from mice sensitized with BeCl2 developed significant footpad swelling 24 and 48 hrs after challenge of BeCl2 as the antigen. (2) After passive transfer with sensitized spleen cells or lymph node cells the ears of the mice were painted with 7% BeCl2 in ethyl alcohol. Ears of these mice showed significant swelling as compared with those of controls. (3) The migration of peritoneal cells from mice receiving spleen or lymph node cells from sensitized mice was inhibited when tested in medium containing the antigen of BeCl2. From our present experiments, it was suggested that the beryllium sensitizing ability was related to active as well as passive cell-mediated immunity.

Animals↗

Influence of spinal and hypothalamic warming on metabolism and sleep in pigeons.

Animals were prepared with electrooculogram (EOG), cortical electroencephalogram (EEG), and electromyogram (EMG) electrodes and with spinal and/or hypothalamic thermodes. Experiments were run at a cold and a neutral ambient temperature (Ta) during the dark portion of a 24-h light-dark cycle. Metabolic rate, temperatures, EEG, EMG, and EOG were measured continuously for 4-h periods with hypothalamic or spinal temperature unmanipulated or warmed to the level measured during the light. The cold Ta increased metabolic rate over the neutral Ta, but did not influence total sleep time (TST) or rapid-eye-movement sleep (REM) as percent TST. At the cold Ta, spinal warming resulted in reduction in REM as a percent TST. Spinal warming frequently caused a fall in body temperature (Ta). A plot of REM as a percent TST vs. the fall in Tb, including data for all animals and all conditions, revealed a clear correlation between fall in Tb and reduction in REM. Hypothalamic warming had no influence on metabolic rate, Tb, or distributions of arousal states. Cold thermal stimuli caused by a fall in Tb can inhibit REM in birds as it can in mammals independently of thermoregulatory drive.

Animals↗