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Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 127 records · Page 7Linked to original sources
PubMed1996

[Drug distribution of pelvic intraarterial infusion chemotherapy by bilateral internal iliac arterial catheter placement with coil occlusion of superior, inferior gluteal and obturator arteries].

The anticancer drug distribution in pelvic arterial infusion chemotherapy with bilateral internal iliac arterial catheter placement with coil occlusion of the superior, inferior and obturator arteries was indirectly evaluated by serially performed DSA, CTA and RI on 18 patients with pelvic malignancies. The distribution was judged to be Excellent (E), defined as uniform distribution in the entire lesion alone, in 9 of 18 patients (50%) evaluated prior to the start of the arterial infusion (AI), and as Good (G), defined as uniform distribution in the entire lesion and partly on an unaffected portion, in 9 (50%). Of the 11 patients evaluated after 7 times AI, E was found in 3 patients (27%), G in 7 (64%) and Fair (F), defined as distribution with a defect in the lesion, in one patient (9%). Of the 11 patients evaluated after 14 AI, E was found in 5 (45%), G in 4 (36%) and F in 2 (18%). Of the 7 patients evaluated after 21 AI, E was found in 2 (29%), G in 4 (57%) and F in one (14%). G was found in 2 of 2 patients (100%) evaluated after 28 AI. These results suggest that this method can maintain a favorable anticancer drug distribution even after multiple sessions of AI.

Adult↗
PubMed1996

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1994 and June 1995].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated by a multicenter study in Japan, and the following results were obtained. One hundred and fifty-three strains were isolated from primary infections, and 143 strains were isolated from postoperative infections. From primary infections, both anaerobic Gram-positive and-negative bacteria were predominant, and from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was highest, followed by that of Staphylococcus aureus from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Streptococcus intermedius was highest from primary infections, but from postoperative infections anaerobic Gram-positive bacteria was uncommon. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order. From postoperative infections, P. aeruginosa was most predominantly isolated, followed by Serratia marcescens and E. coli. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We have noticed that resistant strains against imipenem and ofloxacin were increasing among P. aeruginosa and resistant strains against cefazolin were increasing among E. coli. MICs of cefazolin against four out of 30 strains of E. coli were higher than 100 micrograms/ml, and MICs of imipenem was higher than 50 micrograms/ml against 5 out of 22 strains of P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1996

[Three-dimensional-CT pancreatography under balloon-ERP in the pancreatic diseases--its method and usefulness].

Three-dimensional-CT pancreatography (3D-CTP) under balloon-ERP was carried out in 13 patients with the pancreatic diseases. Tapering stenosis of pancreatic duct in 2 patients out of 2 with pancreatic cancer, shape of cyst and relationship between cyst and pancreatic duct in 7 patients out of 7 with pancreatic cysts, and irregularity of wall of pancreatic duct in 2 patients out of 3 with chronic pancreatitis was reconstructed by 3D-CTP, stereographically. Moreover, the confluence of cyst and pancreatic duct in 3 out of 7 pancreatic cysts did not become clear on balloon-ERP, but it was distinct on 3D-CTP. It is suggested that 3D-CTP is useful in understanding pancreatic diseases stereographically, and can be applied to operative simulation, interventional radiology and differential diagnosis on them.

Adult↗
PubMed1996

[Severe surgical infection with no information in terms of bacteria].

The incidence of bacteria caused postoperative infections was performed at the timing when bacteria or fungi is not yet detected. This period is important for management of postoperative infections. MRSA, E. faecalis, P. aeruginosa and fungi were detected with high frequency irrespective of the surgical area. After the operation of esophageal cancer, the most frequent infection was postoperative pneumonia, and the isolated bacteria was P. aeruginosa frequently. In the cases of gastric cancer, hepato-biliary-pancreas cancer and colorectal cancer, intraabdominal sepsis was the highest incidence, and the isolated bacteria was E. faecalis. In terms of intravenous catheter infection, fungus was common. Thus, it may suggest that we can identify the bacteria caused, and the management for postoperative infections was performed appropriately by using the antibiotics which have the sensitive against the expected pathogen.

Bacterial Infections↗
PubMed1995

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.

Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously developed histologically and serologically evident autoimmune diseases (such as thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis, glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host-like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period after transfer of CD4+CD25- cells prevented these autoimmune developments in a dose-dependent fashion, whereas the reconstitution several days later, or inoculation of an equivalent dose of CD8+ cells, was far less efficient for the prevention. When nu/nu mice were transplanted with allogeneic skins or immunized with xenogeneic proteins at the time of CD25- cell inoculation, they showed significantly heightened immune responses to the skins or proteins, and reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by down-regulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage; elimination/reduction of CD4+CD25+ cells relieves this general suppression, thereby not only enhancing immune responses to non-self Ags, but also eliciting autoimmune responses to certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases.

Animals↗
PubMed1995

Syncope associated with exercise, a manifestation of neurally mediated syncope.

A retrospective review of patients evaluated at a university-based referral hospital was performed to assess the basis for syncope associated with exercise in young patients. Over an 8-year period, 54 consecutive young patients (aged 12 to 30 years) were referred for evaluation of frank syncope. Twelve patients had syncope associated with exercise (group I) and 42 patients had syncope not associated with exercise (group II). Patients underwent physical examination, chest x-ray, 2-dimensional echocardiography, and in selected cases, cardiac catheterization. Head-up tilt-table testing was performed in 11 of 12 group I patients. Ten group I patients had no evidence of structural heart disease: 9 of these 10 (90%) developed syncope with tilt-table testing. Head-up tilt-table testing was performed in 41 of 42 group II patients: 34 (83%) developed syncope with tilt-table testing. Standard cardiac electrophysiologic study was performed in 9 of 12 group I and in 30 of 42 group II patients, and identified a basis for syncope in only 2 group I and 1 group II patients. Among 9 group I patients with a positive result on head-up tilt-table testing and no evidence of structural heart disease (mean follow-up 4.3 years), 7 are without further episodes of syncope; 3 have discontinued medication and 5 have resumed at least limited exercise. In conclusion, susceptibility to tilt-induced syncope was the most frequent finding in young patients without structural heart disease referred for evaluation of exercise-associated syncope. Tilt-table testing may be an important diagnostic tool for the evaluation of these patients.

Adolescent↗
PubMed1995

Pharmacologic treatment of intimal hyperplasia after metallic stent placement in the peripheral arteries. An experimental study.

RATIONALE AND OBJECTIVES: To evaluate the efficacy of oral administration of cilostazol, an antithrombotic agent, for the prevention of thrombotic occlusion and intimal hyperplasia after stenting. METHODS: Single-bodied Z-stents were placed in the iliac arteries of 23 dogs. Before stenting, an embolizing coil was introduced into the right femoral artery to reduce blood flow in the right iliac artery. Eleven dogs were given cilostazol orally, and the other 12 were unmedicated as a control group. The dogs were killed at 4, 13, and 24 weeks. RESULTS: Intraluminal narrowing due to thrombus was observed in 25% of dogs in the control group but in none of the dogs in the cilostazol group. The thickness of the neointima was significantly thinner in the cilostazol group than in the control group at 24 weeks on the noncoiled side (P < 0.05), and at 4 and 24 weeks on the coiled side (P < 0.01). CONCLUSIONS: These results suggest that oral administration of cilostazol is an effective method of preventing thrombotic occlusion and intimal hyperplasia after stenting.

Administration, Oral↗
PubMed1995

Role of Ca2+ on endotoxin-sensitivity by galactosamine challenge: lipid peroxide formation and hepatotoxicity in zymosan-primed mice.

This study was investigated to clarify the role of intracellular Ca2+ following endotoxin treatment (1 mg/kg, intraperitoneally) to D-galactosamine-sensitized mice (400 mg/kg, intraperitoneally), and to observe lipid peroxide levels, an index of hepatotoxicity, in endotoxin/galactosamine (Ga1N)-challenged mice under activation of macrophages, especially Kupffer cells, by zymosan. The liver lipid peroxide level and serum glutamic pyruvic transminase activity in mice 18 hr after administration of endotoxin/Ga1N were markedly higher than those in mice treated only with endotoxin. In spite of an increase in lipid peroxide formation, there was little or no effect of Ga1N administration on xanthine oxidase and superoxide dismutase activities in mice given endotoxin. However, the injection of verapamil (10 mg/kg, subcutaneously) markedly decreased lipid peroxide levels in liver of endotoxin/Ga1N-injected mice. In the mice given a Ca(2+)-deficient diet, lipid peroxide level in liver after endotoxin/Ga1N injection was markedly decreased compared to that in mice fed a normal diet. Administration of dexamethasone (200 micrograms/kg, intraperitoneally) in mice 1 hr before treatment with endotoxin/Ga1N did not induce lipid peroxide formation. Administration of endotoxin to Ga1N-treated mice resulted in a higher level of liver cytosolic free Ca2+ ([Ca2+]i) than that in endotoxin-treated mice. On the other hand, Ca(2+)-ATPase activity in liver plasma membrane in the endotoxin/Ga1N-treated mice was markedly decreased as compared with endotoxin alone. On the contrary, the Ca(2+)-ATPase activity in liver mitochondria was higher in endotoxaemic mice treated with GA1N than in mice given endotoxin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1995

Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent.

Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disease of humans caused by an unidentified infectious agent, the prion. To determine whether there was an involvement of the host-encoded prion protein (PrPc) in CJD development and prion propagation, mice heterozygous (PrP+/-) or homozygous (PrP-/-) for a disrupted PrP gene were established and inoculated with the mouse-adapted CJD agent. In keeping with findings of previous studies using other lines of PrP-less mice inoculated with scrapie agents, no PrP-/- mice showed any sign of the disease for 460 days after inoculation, while all of the PrP+/- and control PrP+/+ mice developed CJD-like symptoms and died. The incubation period for PrP+/- mice, 259 +/- 27 days, was much longer than that for PrP+/+ mice, 138 +/- 12 days. Propagation of the prion was barely detectable in the brains of PrP-/- mice and was estimated to be at a level at least 4 orders of magnitude lower than that in PrP+/+ mice. These findings indicate that PrPc is necessary for both the development of the disease and propagation of the prion in the inoculated mice. The proteinase-resistant PrP (PrPres) was undetectable in the brain tissues of the inoculated PrP-/- mice, while it accumulated in the affected brains of PrP+/+ and PrP+/- mice. Interestingly, the maximum level of PrPres in the brains of PrP+/- mice was about half of the level in the similarly affected brains of PrP+/+ mice, indicating that PrPres accumulation is restricted by the level of PrPc.

Animals↗
PubMed1995

Depressive effect of a traditional Chinese medicine (sho-saiko-to) on endotoxin-induced nitric oxide formation in activated murine macrophage J774A.1 cells.

The present study investigated whether or not Sho-saiko-to (crude powder extract, TJ-9) can suppress nitric oxide (NO) generation by endotoxin-activated J774A.1 cells in order to study the preventive mechanism of Sho-saiko-to against endotoxemia. In this experiment, we estimated the NO2- in the murine macrophage cell line J774A.1 using the Griess method. Our results clearly demonstrated that J774A.1 cells stimulated with endotoxin (0.01-10 micrograms/ml) can effectively produce NO, and the production was dependent on the dose of endotoxin. On the other hand, we investigated the suppressive effect of TJ-9 (10-100 micrograms/ml) on NO generation by endotoxin (0.1 microgram/ml)-activated J774A.1 cells. The NO level when the cells were incubated with endotoxin and TJ-9 (10-20 micrograms/ml) was slightly lower than that in cells treated with endotoxin alone. In contrast, treatment with TJ-9 (50-100 micrograms/ml) significantly inhibited endotoxin-activated NO generation in J774A.1 cells, whereas the treatment with TJ-9 (10-100 micrograms/ml) alone was ineffective in inducing NO formation and in inhibiting cell viability in the J774A.1 cells. These findings suggest that a Kampo presciption of Sho-saiko-to shows a suppressive effect on NO generation in macrophages stimulated with endotoxin, and that it may be useful in improving endotoxin-shock symptoms.

Animals↗
PubMed1994

Multiple-sensor systems for physiologic cardiac pacing.

PURPOSE: To review the status of artificial sensors in cardiac pacemakers and the rationale for developing pacing systems that use multiple sensors. DATA SOURCES: Journal articles published between 1982 and 1993 indexed in MEDLINE using the keywords pacemakers, sensors, and rate-adaptive, as well as abstracts and articles in the authors' personal files. STUDY SELECTION: Articles describing clinical experience with or clinical evaluation of cardiac pacing systems using multiple artificial sensors. DATA SYNTHESIS: Artificial sensors were created to adjust pacing rate reliably in response to changes in levels of physical exertion for patients with sinoatrial disease in whom exercise heart rate response is inadequate (for example, chronotropic incompetence in sinoatrial disease). To achieve this, various artificial sensors were developed and many reports confirm improved exertional tolerance. More recently, sensors have assumed a greater role in cardiac pacemakers. For example, sensors are used to permit automatic adjustment of certain programmable pacemaker settings, such as the atrioventricular interval. In the future, they may also be used to maximize pacemaker longevity by automatically optimizing energy output (voltage, pulse width). No single sensor is ideal for all potential applications, and investigators have advocated using two or more sensors. Several pacemakers that use multiple sensors with different but complementary operating characteristics are already commercially available outside the United States. Although preliminary findings are encouraging, additional clinical experience with these pacemakers is needed to determine their ultimate role in clinical practice. CONCLUSION: Simultaneous use of multiple complementary artificial sensors may permit development of cardiac pacemakers that operate more physiologically yet require less specialized medical follow-up.

Clinical Trials as Topic↗
PubMed1994

Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells.

Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4+ T cells mediated the autoimmune prevention but CD8+ T cells did not. CD4+ T cells also appeared to mediate the TLI-induced autoimmune disease because CD4+ T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells.

Animals↗
PubMed1994

Induction of autoimmune disease in mice by germline alteration of the T cell receptor gene expression.

Germline expression of rearranged TCR alpha-chain transgenes with the Ig H chain enhancer reproducibly elicits T cell-mediated autoimmune disease in the thyroid gland, gastric mucosa, Langerhans islets, salivary gland, ovaries, and testes in selected strains of normal mice. Multiple organs are destroyed in a single transgenic mouse and the same organ in transgenic strains with different MHC background, suggesting the transgene expression can elicit self-reactive T cell clones having different Ag specificities and MHC restrictions. Construction of this autoimmune-inducing TCR alpha EH transgene does not require particular V alpha J alpha gene segments or Ag specificities. Moreover, the autoimmune disease can be adoptively transferred to syngeneic normal mice by T cells expressing endogenous TCR alpha-chains. Taken together, these results indicate that the TCR alpha EH transgene expression does not suppress endogenous alpha-chain gene rearrangement and may trigger the expansion/activation of various self-reactive T cells expressing endogenous TCR alpha- and beta-chains. Furthermore, it appears that the transgene-induced autoimmune T cells are not deleted in the normal thymus or rendered anergic upon contact with the normal target self Ag, but can be controlled by a T cell-dependent mechanism, since transfer of the transgenic bone marrow cells to histocompatible SCID mice produces the same autoimmune disease as in the donors, and the autoimmune development in the SCID mice is effectively prevented by co-transfer of syngeneic nontransgenic T cells. This novel autoimmune model produced by genetic manipulation of the T cell lineage, not the target self Ag or the environment of T cell differentiation/selection, should be useful for elucidating the immunologic and genetic basis of autoimmune disease.

Age Factors↗
PubMed1994

Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice.

We have previously shown that continuous administration of anti-interleukin 10 (anti-IL-10) antibodies (Abs) to BALB/c mice modifies endogenous levels of autoantibodies, tumor necrosis factor alpha (TNF-alpha), and interferon gamma, three immune mediators known to affect the development of autoimmunity in "lupus-prone" New Zealand black/white (NZB/W)F1 mice. To explore the consequences of IL-10 neutralization in NZB/W F1 mice, animals were injected two to three times per week from birth until 8-10 mo of age with anti-IL-10 Abs or with isotype control Abs. Anti-IL-10 treatment substantially delayed onset of autoimmunity in NZB/W F1 mice as monitored either by overall survival, or by development of proteinuria, glomerulonephritis, or autoantibodies. Survival at 9 mo was increased from 10 to 80% in anti-IL-10-treated mice relative to Ig isotype-treated controls. This protection against autoimmunity appeared to be due to an anti-IL-10-induced upregulation of endogenous TNF-alpha, since anti-IL-10-protected NZB/W F1 mice rapidly developed autoimmunity when neutralizing anti-TNF-alpha Abs were introduced at 30 wk along with the anti-IL-10 treatment. Consistent with the protective role of anti-IL-10 treatment in these experiments, continuous administration of IL-10 from 4 until 38 wk of age accelerated the onset of autoimmunity in NZB/W F1 mice. The same period of continuous IL-10 administration did not appear to be toxic to, or cause development of lupus-like autoimmunity in normal BALB/c mice. These data suggest that IL-10 antagonists may be beneficial in the treatment of human systemic lupus erythematosus.

Animals↗
PubMed1994

Low-energy transvenous cardioversion defibrillation of atrial tachyarrhythmias in the canine: an assessment of electrode configurations and monophasic pulse sequencing.

Prevention of recurrent atrial fibrillation and flutter remains a difficult clinical problem. Consequently, development of an easily implantable automatic atrial cardioverter defibrillator is appealing. In this context we have examined the feasibility of intracavitary low-energy shocks delivered via transvenously positioned electrodes for termination of induced atrial tachyarrhythmias in canine models. This study extends these observations with use of single-pathway (5 msec pulse duration) and dual-pathway sequential (5/5 msec, 0.2 msec separation) shocks of varying leading edge voltages (100 to 400 V) in a closed-chest canine talc-pericarditis model. Bipolar 9.5 French electrode catheters (electrode surface areas, 0.62 cm2) were positioned at the superior vena cava-right atrium (SVC-RA) junction (labeled SVC) and right ventricular (RV) apex, with a subcutaneous plate over the chest wall. For single-pathway shocks, overall treatment effectiveness was comparable among the three vectors tested (RV apex to SVC, 35%; RV apex to subcutaneous plate, 17%; and SVC to subcutaneous plate, 35%). Furthermore, there was no evident relationship between leading edge voltage and shock effectiveness. In contrast, although each of the dual-pathway shock vector combinations tested also showed similar overall effectiveness, there was an apparent dose-response effect as leading edge voltage increased. The SVC (common) to RV apex (pulse 1) and subcutaneous plate (pulse 2) achieved 60% effectiveness at 400 V (approximately 4 joules). Thus this study provides additional evidence favoring feasibility of low-energy transvenous atrial cardioversion defibrillation. However, further refinement of energy delivery is essential for the implantable automatic atrial cardioverter defibrillator concept to become clinically accepted.

Animals↗
PubMed1994

Occurrence of chromosome rearrangements during the fusion process in the imperfect yeast Candida albicans.

Auxotrophic derivatives of three strains of the pathogenic yeast Candida albicans of different origins, including 1006 derived from CBS5736, A5153 derived from FC18 and NARA2 derived from NUM961, were used in spheroplast fusion experiments. The DNA content of the prototrophic fusion product obtained following fusion between strains 1006 and A5153 approximated to the sum of those of the parents, but was variable when NARA2 was used as the parent for fusion. Chromosome-sized DNA molecules of the fusion derivatives were separated by pulsed-field gel electrophoresis to examine whether either or both of the chromosome-sized DNA molecules of each parent were transferred into the fusion derivatives. In the fusion derivatives obtained following fusion between strains 1006 and A5153, nearly the full complement of chromosomes was shown to be transferred, but partial transfer of chromosomes occurred in the fusion derivatives that were obtained following fusion between strains NARA2 and A5153. Results indicated that chromosome loss also occurred when these two strains were fused. Variations in the size of R chromosomes, the rDNA-containing chromosomes, were observed in all fusion derivatives tested, indicating high-frequency recombination between R chromosomes during the fusion process.

Candida albicans↗