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Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 91 records · Page 5Linked to original sources
PubMed1999

Prehospital discharge defibrillation testing in ICD recipients: a prospective study based on cost analysis.

Prehospital discharge defibrillation testing is often performed to verify the function of newly implanted cardioverter defibrillators (ICDs). To determine whether elimination of predischarge testing could reduce costs without placing patients at additional risk, 31 patients were randomized in this prospective clinical evaluation to either receive or not receive a predischarge ICD defibrillation test. Expenses associated with postimplant care was the primary endpoint. All patients underwent induction of ventricular fibrillation after 6 months to evaluate ICD function. The groups were well matched in terms of patient characteristics, initial lead implant parameters, and defibrillation thresholds. Elimination of prehospital discharge testing resulted in a savings of $1,800/patient after 6 months, with no difference between groups in terms of ICD complication rates or unanticipated hospital admissions. Further studies are needed to better define the most appropriate time to assess defibrillation thresholds in the first year after implantation.

Aged↗
PubMed1999

Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on interleukin-12 production in patients with HCV-positive liver cirrhosis.

Interleukin-12 (IL-12) is an important cytokine for maintenance of normal systemic defense and bioregulation. The Japanese herbal medicine Sho-saiko-to (TJ-9) has been administered to 1.5 million Japanese patients with chronic liver diseases. TJ-9 is known to significantly suppress cancer development in the liver and has macrobiotic effects. In the present study, we examined the in vitro production of IL-12 by circulating mononuclear cells from liver cirrhosis patients and the effects of TJ-9 on IL-12 production. The monocyte/macrophage fraction and the lymphocyte fraction of peripheral blood were obtained from 11 HCV-positive liver cirrhosis patients and 12 healthy subjects. Interleukin-12 levels in the supernatants were measured using ELISA kits. The levels of IL-12 produced by the patients' fractions were significantly lower than those produced by healthy subjects (p < 0.01, p < 0.05). However, when TJ-9 was added to the cultures, the IL-12 production levels in both cell fractions increased approximately three fold, and the levels from the monocyte/macrophage fraction were almost the same as those from healthy subjects. This effect of TJ-9 was attributable to two of its seven herb components, that is, scutellaria root and glycyrrhiza root. One possible mechanism for the macrobiotic effects of TJ-9 on liver cirrhosis patients may be the improvement in IL-12 production.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

A case of primary antiphospholipid antibody syndrome with acute renal failure showing thrombotic microangiopathy.

An 18-year-old woman complained of fever and edema and was admitted to Showa University Hospital for treatment of thrombocytopenia and deteriorating renal function. Laboratory studies demonstrated the presence of lupus anticoagulant (LA), prolongation of prothrombin time, hemolytic anemia, a negative Coombs' test, the absence of antinuclear antibodies, and a normal fibrinogen level. Renal biopsy revealed mesangial hypercellularity, severe endocapillary cell damage, and double contour of the basement membrane walls. Immunofluorescence studies demonstrated focal, peripheral, and finely granular deposits for IgG, IgM, and IgA but were negative for fibrinogen. Electron microscopy showed glomerular capillary loops with subendothelial widening and subendothelial deposits, mesangiolysis, mesangial interposition, and marked luminal narrowing. Biopsy findings were consistent with thrombotic microangiopathy. The patient was treated with hemodialysis, methylprednisolone pulse therapy, and dipyridamole. After treatment, LA disappeared, the prothrombin time became normal, and renal function improved. The renal lesions in this patient were caused by primary antiphospholipid antibody syndrome. This case strongly suggests an important causal relationship between LA and renal lesions in thrombotic microangiopathy. We present this case to promote understanding of the pathogenesis of primary antiphospholipid antibody syndrome.

Acute Kidney Injury↗
PubMed1999

Delayed ischemic hyperintensity on T1-weighted MRI in the caudoputamen and cerebral cortex of humans after spectacular shrinking deficit.

BACKGROUND AND PURPOSE: Transient internal carotid artery (ICA)-middle cerebral artery (MCA) occlusion caused by cardiogenic embolus can lead to spectacular shrinking deficit (SSD): sudden hemispheric stroke syndrome followed by rapid improvement. The aim of this study was to investigate sequential neuroradiological changes in the brains of patients after SSD compared with those after brief cardiac arrest and hypoglycemia, which we previously studied with the same methods. METHODS: We serially studied CT scans and MR images obtained at 1.5 T in 4 patients with SSD. All 4 patients suffered from transient neurological deficits due to cardiogenic embolus in ICA-MCA. The symptoms began to disappear from 25 to 50 minutes after onset. RESULTS: Repeated CT scans demonstrated no abnormal findings in the affected cerebral hemisphere in 3 of the 4 patients and a small cortical infarct in the remaining 1. In each patient, repeated MRI between day 7 and month 23 after stroke showed basal ganglionic and cortical lesions. These lesions were hyperintense on T1-weighted and relatively hypointense on T2-weighted imaging. These ischemic lesions of hyperintensity on T1-weighted MRI subsided with time. CONCLUSIONS: Transient ICA-MCA occlusion leading to SSD produces a specific ischemic change with delayed onset in the basal ganglia and cerebral cortex in humans on MRI but not CT scans. We speculate that the lesions represent incomplete ischemic injury, including selective neuronal death, proliferation of glial cells, paramagnetic substance deposition, and/or lipid accumulation. Unlike brief cardiac arrest or hypoglycemia, the localized lesions on MRI of patients after SSD seem to be incomplete and to differ from infarction or hemorrhage.

Aged↗
PubMed1999

A mouse prion protein transgene rescues mice deficient for the prion protein gene from purkinje cell degeneration and demyelination.

Disruption of both alleles of the prion protein gene, Prnp, renders mice resistant to prions; in a Prnp o/o line reported by some of us, mice progressively developed ataxia and Purkinje cell loss. Here we report torpedo-like axonal swellings associated with residual Purkinje cells in Prnp o/o mice, and we demonstrate abnormal myelination in the spinal cord and peripheral nerves in mice from two independently established Prnp o/o lines. Mice were successfully rescued from both demyelination and Purkinje cell degeneration by introduction of a transgene encoding wild-type mouse cellular prion protein. These findings suggest that cellular prion protein expression may be necessary to maintain the integrity of the nervous system.

3' Untranslated Regions↗
PubMed1998

Physiologic cardiac pacing in patients with contemporary implantable cardioverter-defibrillators.

Contemporary implantable cardioverter-defibrillators (ICD) incorporate single-chamber ventricular pacing capability. However, because poor ventricular function and/or congestive heart failure is common in the ICD population, the provision of more "physiologic" pacing modes has been receiving increased attention. To evaluate the potential impact of ICDs with physiologic pacing features, we assessed the frequency with which atrial-based pacing modes with or without rate responsiveness are currently used in ICD recipients. Further, we characterized those clinical variables at initial ICD implant that tended to be associated with subsequent need for physiologic pacing. Clinical findings were reviewed in 250 consecutive patients who received ICDs with VVI pacing capability at the University of Minnesota Cardiac Arrhythmia Center between January 1991 and February 1997. Adjunctive physiologic pacing was undertaken in 35 patients (14%): 13 before or at the same time as their ICD, and 22 within a mean of 2.5 years after initial ICD surgery. A history of atrial tachyarrhythmia before ICD implantation (p <0.0001) and treatment with antiarrhythmic drugs at the time of ICD surgery (p <0.05) were predictors of subsequent need for physiologic pacing. The type of presenting ventricular tachyarrhythmia and electrophysiologic parameters (such as the HV interval and the shortest atrial pacing cycle length associated with 1:1 anterograde atrioventricular conduction) were not associated with a subsequent decision to implant a physiologic pacing system. Thus, we conclude that despite the need to implant a second device, physiologic pacing is currently used in an important subset of ICD recipients. Further, certain clinical features at time of ICD implant appear to characterize these patients and may prove helpful in patient selection for the next generation "dual-chamber" ICD.

Adolescent↗
PubMed1998

Impaired motor coordination in mice lacking prion protein.

1. Prion protein (PrPC) is a host-encoded glycoprotein constitutively expressed on the neuronal cell surface. Accumulation of its protease-resistant isoform is closely related to pathologic changes and prion propagation in the brain tissue of a series of prion diseases. However, the physiological role of PrPC remains to be elucidated. 2. After long-term observation, we noted impaired motor coordination and loss of cerebellar Purkinje cells in the aged mice homozygous for a disrupted PrP gene, a finding which strongly suggests that PrPC plays a role in the long-term survival of Purkinje cells. 3. We also describe the resistance of the PrP null mice to the prion, indicating the requirement of PrPC for both the development of prion diseases and the prion propagation.

Animals↗
PubMed1998

Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state.

Elimination of CD25+ T cells, which constitute 5-10% of peripheral CD4+ T cells in normal naive mice, leads to spontaneous development of various autoimmune diseases. These immunoregulatory CD25+CD4+ T cells are naturally unresponsive (anergic) in vitro to TCR stimulation, and, upon stimulation, suppress proliferation of CD25-CD4+ T cells and CD8+ T cells. The antigen concentration required for stimulating CD25+CD4+ T cells to exert suppression is much lower than that required for stimulating CD25-CD4+ T cells to proliferate. The suppression, which results in reduced IL-2 production by CD25-CD4+ T cells, is dependent on cellular interactions on antigen-presenting cells (and not mediated by far-reaching or long-lasting humoral factors or apoptosis-inducing signals) and antigen non-specific in its effector phase. Addition of high doses of IL-2 or anti-CD28 antibody to the in vitro T cell stimulation culture not only breaks the anergic state of CD25+CD4+ T cells, but also abrogates their suppressive activity simultaneously. Importantly, the anergic/suppressive state of CD25+CD4+ T cells appeared to be their basal default condition, since removal of IL-2 or anti-CD28 antibody from the culture milieu allows them to revert to the original anergic/suppressive state. Furthermore, transfer of such anergy/suppression-broken T cells from normal mice produces various autoimmune diseases in syngeneic athymic nude mice. These results taken together indicate that one aspect of immunologic self-tolerance is maintained by this unique CD25+CD4+ naturally anergic/suppressive T cell population and its functional abnormality directly leads to the development of autoimmune disease.

Animals↗
PubMed1998

Comparison of right atrial and peripheral procainamide infusion levels in patients with spontaneous or induced atrial fibrillation.

As part of a new effort to develop an implantable drug infusion/pacing system to treat atrial fibrillation, this study examined the effects of rapid intracardiac procainamide infusion in humans with pacing-induced atrial fibrillation. Twenty patients with atrial fibrillation for > 5 minutes during an EP study received 500 mg of procainamide either via a peripheral venous infusion (n = 5) or directly in the right atrium (n = 15). Peak coronary sinus and femoral vein procainamide blood levels (mean +/- SEM) during 10, 5, and 3.3 minute central infusions were 17.0 +/- 4.1, 25.1 +/- 4.5, 45.6 +/- 5.1 and 11.3 +/- 3.2, 17.1 +/- 6.4, 18.7 +/- 5.0, respectively. In contrast, peak coronary sinus and femoral procainamide levels following the 5 minute intravenous infusion were 17.7 +/- 5.1 and 9.3 +/- 2.1. Changes in QT, QTc, QRS, and RI intervals were similar at each infusion rate. Systolic blood pressures (BP) decreased more with higher procainamide infusion rates but similar when comparing intravenous versus central drug administration at the same rate. The mean +/- SEM decreases in blood pressure with the 10, 5, and 3.3 min procainamide infusions were 12f5, 20f11, and 39f14, respectively. Conversion to sinus rhythm was not a primary endpoint given the often transient nature of acute atrial fibrillation in this setting. We conclude that significantly higher femoral vein and coronary sinus procainamide levels can be achieved by central rather than peripheral drug infusion. These data support that concept that rapid central infusion of anti-arrhythmic therapy can result in high intracardiac levels of antifibrillatory agents for the treatment of paroxysmal atrial fibrillation.

Adult↗
PubMed1998

Percutaneous retroperitoneal splenorenal shunt: an experimental study in swine.

PURPOSE: To evaluate the technical possibility of creating a percutaneous retroperitoneal splenorenal shunt (PRESS) in swine as a minimally invasive treatment of portal hypertension. MATERIALS AND METHODS: Five normal domestic swine underwent creation of a PRESS. A modified transjugular intrahepatic portosystemic shunt puncture set was introduced from the right femoral vein into the left renal vein. The proximal splenic vein was punctured transvenously through the retroperitoneal cavity. Noncovered metallic stents were then placed to connect both veins. The animals were sacrificed 1 hour after the procedure, after follow-up splenic venography and necropsy were performed. RESULTS: Puncture of the splenic vein and stent placement were successfully completed in all cases. In four of five cases, the splenic venogram revealed good flow from the splenic vein to the left renal vein through the shunt track 1 hour after creation of the PRESS, and there was no evidence of leakage. No changes in vital signs were noticed. At necropsy, a small retroperitoneal hematoma along the stent and minimal intraperitoneal bleeding were observed. The stents were found in the retroperitoneal cavity connecting both veins in all animals. CONCLUSION: Creation of a PRESS is technically possible, and further experimental studies of its efficacy are warranted.

Animals↗
PubMed1998

[Immunotoxicity of beryllium].

The lymphocyte transformation test and the macrophage migration inhibition test are quantitative methods invaluable for examination of beryllium (hereafter referred to as Be) effects on cell-mediated immunity. We recognized that the Be sensitizing ability was related to active as well as passive cell-mediated immunity in mice subcutaneously injected with Be once a week over a 6-week period. Be also affects B cells, and it increases the amount of immunoglobulins in sera. In the study of immunological health surveys of Be workers in a copper-beryllium casting factory, the serum complement titer tended to be lower in Be workers than in the controls. In mice, injected with Be once a week over a 12-week period, serum complement titers decreased. Correlation coefficients of the experimental parameters showed a significant negative correlation between the complement titers and the prothrombin time or the coagulation time for factor VII, using mice injected with 5 micrograms of Be. It was suggested that increases in the complement titers after Be administration may be induced by temporarily-activated plasma serin protease, which is a component of blood coagulation factor VII. The delta-aminolevulinic acid dehydratase and porphobilinogen deaminase activities were significantly elevated in the pregnant untreated group, compared with the nonpregnant mice (the control group). However, it was noted that these values in the pregnant mice injected with 50 micrograms of Be were almost the same as the values of the controls. It suggests that Be suppressed the expected pregnancy-induced increase in hematopoietic function. There are at least two risk factors induced in the effects of beryllium on organisms-exposure to the metal and inheritance of the genetic marker. It is necessary to reduce exposure, to give preventive education and to carry out periodic health examinations for the prevention of disease induced by Be.

Animals↗
PubMed1998

[Transarterial enhanced ultrasonography examination of hepatocellular carcinoma using CO2].

The findings of enhanced ultrasonography under the injection of microbubbles of carbon dioxide into a hepatic artery (CO2-US) were evaluated in the patients with hepatocellular carcinoma (HCC). They were as follows. Most nodules showed early (within 3 seconds) stronger enhancement compared to the surrounding hepatic parenchyma, remaining the enhancing effects more longer than the surround. A few nodule showed isoenhance or nonenhancement. However, metastatic cancer of the liver often showed the early enhancement only at the edge of tumor. In hepatic hemangioma, only the spotty enhancement in the tumor and or the later (later than 4 seconds) enhancement at the edge of tumor was showed. The hyperenhanced mass was detected more often in a larger HCC and revealed to be a relatively poorly differentiated HCC with the capsule formation.

Carbon Dioxide↗
PubMed1998

[Transcatheter arterial embolization of hepatocellular carcinoma using CO2-US].

Enhanced ultrasonography under the injection of microbubbles of carbon dioxide into the hepatic artery (CO2-US) contributed to the treatment of hepatocellular carcinoma in the selection of indication of transcatheter arterial embolization (TAE). Judging from the accumulation of the lipiodol after TAE with the combination of lipiodol, TAE was thought to be effective in the tumor which was enhanced by CO2 microbubbles more strongly and the enhancement was prolonged more longer compared to the surrounding parenchyma, even the tumor had no tumor staining on the hepatic angiography. In none of the tumor which had no enhancement, TAE was effective. In most of the tumor with isoenhancement compared with surrounding parenchyma TAE was not effective.

Carbon Dioxide↗
PubMed1997

Termination of implantable pacemaker therapy: experience in five patients.

BACKGROUND: Established guidelines direct the initial implantation of permanent pacemakers. Elective replacement of these devices is common. However, no guidelines exist for the removal of permanent pacemakers and the termination of long-term cardiac pacing. OBJECTIVE: To describe the feasibility and safety of terminating cardiac pacing in carefully selected patients. DESIGN: Case series. SETTING: University hospital. PATIENTS: Five adults with permanent pacemakers who were referred for pacemaker replacement or a complication related to cardiac pacing. All patients showed alleviation or reversal of the electric disturbance that originally led to the implantation of the device. The patients had received a pacemaker for a class I or II indication (that is, symptomatic bradycardia or asymptomatic, persistent third-degree atrioventricular block at the level of the atrioventricular node). INTERVENTION: After an appropriate natural rhythm was documented, pacemakers were removed from all patients. MEASUREMENTS: Time without recurrence of symptomatic bradycardia. RESULTS: No patient had recurrent symptomatic bradycardia after 18 to 48 months of clinical follow-up. CONCLUSIONS: The presence of a permanent pacemaker does not necessarily imply a permanent need for cardiac pacing. Discontinuation of cardiac pacing may be considered in certain patients. Establishing consensus criteria about the potential indications, methods, and timing of the termination of cardiac pacing seems appropriate.

Adult↗
PubMed1997

Effect of beryllium chloride on porphyrin metabolism in pregnant mice administered by subcutaneous injection.

The effect of beryllium (Be) compounds on porphyrins was investigated in pregnant mice. The blood protoporphyrin (Proto) and zinc protoporphyrin (Zn Proto) concentrations were increased in pregnancy. Regardless of pregnancy or nonpregnancy, the Proto concentration was decreased after Be injection. Delta-aminolevulinic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D) activities in blood were significantly elevated in the pregnant untreated (Con-pregnant) group, compared to the nonpregnant mice untreated (Con-nonpregnant) and nonpregnant mice treated with Be (Be-nonpregnant) groups. The blood ALA-D activity of the pregnant mice treated with Be (Be-pregnant group) tended to decrease, compared to Con-pregnant group. The blood PBG-D activity in the Be-pregnant group was significantly lower compared with that of the Con-pregnant group. The ALA-D and PBG-D activities in the spleen were also significantly elevated in the Con-pregnant group, compared to nonpregnant groups. However, it was noted that these values in the Be-pregnant group were almost the same as that of the Con-nonpregnant group and were significantly lower than that in the Con-pregnant group. The elevation of ALA-D and PBG-D activities in the blood and spleen, which play a role in the hematopoietic function of mice, was observed in the Con-pregnant mice compared to the nonpregnant mice. However, the phenomenon was not observed in the Be-pregnant mice, it suggesting that Be suppressed the pregnancy-induced increase in hematopoietic function.

Animals↗
PubMed1997

Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on in vitro interleukin-10 production by peripheral blood mononuclear cells of patients with chronic hepatitis C.

"Sho-saiko-to" (TJ-9) consists of 7 herbal components. In Japan, it is widely prescribed to patients with chronic viral liver disease. TJ-9 is known to suppress liver cancer development and possess macrobiotic effects, but its mode of action is not fully understood. This study investigated the following: 1) cytokine production levels, mainly interleukin (IL)-10, in peripheral blood mononuclear cells of chronic active hepatitis B and C patients, and healthy volunteers; 2) effects of TJ-9 on these productions; and 3) effects of each of its herb components on cytokine production in cell fractions. Results showed that without stimulants, IL-10 production in mononuclear cells of hepatitis B and C patients was significantly lower than that of healthy subjects (P < .01). IL-10 production induced by either phytohemagglutinin (PHA) or pokeweed mitogen (PWM) in mononuclear cells of hepatitis C patients were significantly lower than in patients with hepatitis B (P < .01) and healthy subjects (P < .05). IL-10 production induced by anti-CD3 or lipopolysaccharide (LPS) was significantly lower than in healthy subjects (P < .05). The addition of TJ-9 to the cultures strongly induced IL-10, and this induction was mainly attributable to the effects of 2 components (scutellaria root and glycyrrhiza root) on the monocyte/macrophage fraction. The production of IL-4 and IL-5 in cultures with concanavalin A (conA) was significantly higher in patients with hepatitis C than in the healthy subjects (P < .01; P < .05), but the addition of TJ-9 suppressed these increases by 25% to 33% (P < .01). Therefore, TJ-9 could adjust the decreased IL-10 production and the increased IL-4 and IL-5 production of mononuclear cells from patients with hepatitis C. Moderate regulation of the cytokine production system in patients with hepatitis C by using TJ-9 may be useful in the prevention of disease progression.

Adult↗