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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 325 records · Page 18Linked to original sources
PubMed1996

Ca(2+)-dependent activation of the 33-kDa protein kinase transmits thrombin receptor signals in human platelets.

Thrombin stimulation induces a dramatic increase in the activity of the 33-kDa serine/threonine kinase (PK33) in human platelets (10). The Arg-Gly-Asp (RGD) peptide, an inhibitor of the thrombin-mediated aggregation of platelets, did not affect the PK33 activation induced by thrombin suggesting that the activation of this kinase occurs independently from platelet aggregation. To identify a potential role of Ca2+ and calmodulin in the regulation of PK33, the effect of several Ca2+/calmodulin inhibitors on the thrombin-induced activation of PK33 was assessed using denaturation/renaturation method. Pretreatment of platelets with EGTA decreased the maximum PK33 activity induced by thrombin. The chelation of both the extra- and the intracellular Ca2+ by EGTA and by acetoxymethyl ester of 5,5'-dimethyl-bis-(0-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) decreased further the PK33 activation by thrombin. Preincubation of platelets with the anticalmodulin agent, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide (W13), inhibited markedly the activation of PK33 by thrombin, whereas the inactive structural analog N-(4-aminobutyl)-2-naphthalenesulfonamide (W12) and the myosin light chain kinase inhibitor 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML9) showed very weak inhibitory effects. Treatment of resting platelets with the calcium ionophore, A23187, activated PK33 in a dose-dependent manner; phorbol 12-myristate 13-acetate enhanced this effect. However, the two foregoing agents did not induce similar degree of PK33 activities as thrombin. These results indicate that the activation of PK33 is independent of the formation of the GPIIb/IIIa-fibrinogen complex and that it might be regulated by a Ca(2+)-dependent pathway.

Blood Platelets↗
PubMed1995

GABA rho1 receptor: inhibition by protein kinase C activators.

The effects of protein kinase C (PKC) activators on gamma-aminoburyric acid (GABA) rho 1 receptor function were studied in rho 1 -expressing Xenopus oocytes. The PKC activator phorbol 12-myristate 13-acetate (PMA) but not the inactive analog phorbol 12-mono-myristate inhibited the GABA-gated chloride currents. Mezerein, a non-phorbol ester type PKC activator, also inhibited the rho 1 responses, but 8-chlorophenylthio-cyclic AMP, a protein kinase A activator, had no effect. The effect of PMA was significantly reduced by a PKC inhibitor, staurosporine. These results suggest that GABA rho 1 receptor function can be regulated by PKC-mediated phosphorylation events.

Alkaloids↗
PubMed1995

Fas receptor (CD95)-mediated apoptosis is induced in leukemic cells entering G1B compartment of the cell cycle.

Apoptotic cell death induced by cross-linking Fas receptor (FasR/CD95) has been investigated in human acute myelogenous leukemia (AML) cells. FasR-mediated growth inhibition and DNA fragmentation could be induced in certain cases of AML. Interestingly, when DNA synthesis and G1 -> S transition in the cell cycle were enhanced by interleukin-3 or granulocyte-macrophage colony-stimulating factor, Fas-insensitive blast cells acquired cellular susceptibility toward FasR-mediated growth inhibition. To further evaluate an association between the Fas-R-mediated action and a specific phase of the cell cycle, a FasR+ leukemic cell line, MML-1, was established from a patient with AML. The morphologic feature of dying cells and DNA fragmentation indicated that FasR cross-linking induced apoptotic cell death in MML-1 cells. Cell cycle arrest in G1A phase with the treatment of phorbol 12-myristate 13-acetate or thymidine rendered MML-1 cells resistant to FasR-mediated apoptosis without downregulation of surface FasR expression. However, S-phase arrest with 5-fluorouracil could neither enhance nor inhibit FasR-mediated apoptosis. Simultaneous DNA/RNA quantification analysis revealed the selective loss of cells in G1B compartment, accompanied by the increase of apoptotic nuclei in sub-G1 fraction. These findings suggested that FasR-mediated apoptotic signals could be transduced into cells in G1B compartment and G1A -> G1B transition might augment the induction of FasR-mediated apoptosis.

Acute Disease↗
PubMed1995

Accelerated cell-cycling of hematopoietic progenitor cells by growth factors.

Recent advances in molecular biology have led to the identification of hematopoietic growth factors that support and influence the proliferation of hematopoietic progenitor cells in vitro and in vivo. Although these factors have been extensively studied, little is known of their role in the regulation of cell-cycling of hematopoietic progenitors, especially in the early stage of hematopoiesis. In the present study, we examined the effects of early acting growth factors on proliferative kinetics of hematopoietic progenitors by monitoring the number of cells in individual developing colonies, using an in vitro clonal assay. Interleukin-11 (IL-11) or steel factor (SF), alone or in combination, shortened the time for the size of IL-3-dependent colonies to double. Consecutive replating experiments provided evidence for direct action of growth factors on the growth rate of hematopoietic progenitor cells. Shortening of the time for the total cell number in the colonies to double was due to a reduction in time for each single cell within the respective colonies to become two daughter cells, and there was no alteration in the incidence of cells with a proliferative capacity. Cell-cycle analysis demonstrated that IL-11 has the potential to induce a shortened time for cell-cycle of hematopoietic progenitor cells without affecting distribution of each fraction of the cell-cycle, whereas SF has the potential to reduce cell-cycle time mainly by decreasing the time required for hematopoietic progenitor cells to go through the G1 phase. These results suggest that growth factors may modulate cell-cycling of hematopoietic progenitor cells.

Animals↗
PubMed1995

Post-synaptic depolarization in induction of long-term potentiation in the CA1 hippocampus.

The role of dendritic depolarization in the induction of long-term potentiation (LTP) was studied in the CA1 hippocampus in vitro. In Mg(2+)-free medium, conditioning stimuli of 50 pulses at 1 Hz induced LTP (1 Hz LTP). This LTP was blocked by APV. To block dendritic depolarization, GABA or muscimol was applied iontophoretically to the dendritic region in conjunction with each conditioning stimulus. This procedure blocked 1 Hz LTP, even though a larger than normal Ca2+ influx through the NMDA receptor channels was expected due to an increase in electromotive force. These results suggest that depolarization is required, in addition to unblocking Mg2+ from NMDA receptor channels, most likely to open voltage-gated calcium channels.

Animals↗
PubMed1995

Indocyanine green fundus angiography of retrobulbar vasculature.

OBJECTIVE: To report the observations of the retrobulbar vasculature with indocyanine green angiography. METHODS: We performed fluorescein and indocyanine green angiography with a fundus camera (TRC501A) at a university medical center. We examined 12 patients (three men and nine women) with pathologic myopia. RESULTS: With these methods, retrobulbar vessels could be observed in the eyes of these patients with pathologic myopia and thin sclera. The location of the vessels could be changed by altering eye position. CONCLUSION: With fluorescein angiography, we were able to visualize some of the retrobulbar vasculature in selected areas, but indocyanine green angiography was apparently superior to fluorescein angiography.

Adult↗
PubMed1995

Serosal balls detected immunocytochemically in peritoneal lavage obtained during surgery.

Using the immunoperoxidase technique, we studied "serosal balls," which have features resembling those of cells from primary and metastatic tumors, and may thus complicate cytodiagnosis. Serosal balls were detected in 32 (18%) of 174 peritoneal washings. The balls consisted of oval clusters of cells in solid masses surrounded by flattened cells. The interior of the serosal balls was stained green with Papanicolaou method, showing the presence of homogeneous amorphous material, sometimes stained in a filamentous pattern. Almost all serosal balls were stained immunocytochemically for both keratin and vimentin. The interior was stained with antibodies against collagen types I and III. Therefore, these balls were fragments of serous membrane, and contained fibrous tissue and mesothelial cells.

Azure Stains↗
PubMed1995

Changes of adhesion molecule (LFA-1, ICAM-1) expression on memory T cells activated with cytomegalovirus antigen.

The expression of adhesion molecules (LFA-1, ICAM-1, CD29) on T cells activated with cytomegalovirus (CMV) antigen was investigated by three-color flow cytometry analysis. Peripheral blood mononuclear cells (PBMC) from CMV-seropositive adults were cultured with CMV or control antigen for 6 days. After culture, the expression of LFA-1, ICAM-1, and CD29 on T cells in subpopulations defined as CD45RO+ or CD45RO- was analyzed. The population of cells that expressed LFA-1 at high levels (LFA-1high) among CD4+C-D45RO+ cells increased when cultured with CMV antigen compared to control antigen. The population of cells that expressed LFA-1high cells among CD8+C-D45RO+ cells was down-regulated by culture for 6 days; however, the population of LFA-1high cells among CD8+CD45RO+ cells cultured with CMV antigen was higher than when cultured with control antigen. The population of LFA-1high cells among CD4+CD45RO- and CD8+CD45RO- cells did not change after culture with CMV antigen. The intensity of CD29 and expression of ICAM-1 also increased on both CD4+CD45RO+ and CD8+CD45RO+ cells after culture with the CMV antigen. Up-regulation of adhesion molecules occurred on activated T cells by culture with the CMV antigen. This change was observed mainly on CD45RO+ T memory cells. The results suggested that these changes of adhesion molecules on activated T cells with CMV may contribute to some immune reaction or inflammatory change.

Adult↗
PubMed1995

Fas antigen and bcl-2 expression on lymphocytes cultured with cytomegalovirus and varicella-zoster virus antigen.

Fas antigen and bcl-2 expression on peripheral blood mononuclear cells (PBMC) cultured with cytomegalovirus (CMV) and varicella-zoster virus (VZV) antigen was analyzed by three-color flow cytometry. Expression of Fas antigen increased significantly in CD45RO+ populations of both CD4+ and CD8+ cells obtained from CMV and VZV seropositive donors after culture with CMV and VZV antigen for 6 days. Fas antigen expression did not increase in PBMC cultured with control antigen. In contrast, bcl-2 expression decreased both in CD4+CD45RO+ and CD8+CD45RO+ cells from the same donors. Fas antigen and bcl-2 expression in CD45RA+ populations did not change. Cell viability of cultured cells with CMV and VZV antigen decreased after treatment with anti-Fas antibody and DNA fragments indicating apoptosis were detected in the cell lysate of these cultured cells after treatment with anti-Fas antibody. These data suggest that Fas antigen and bcl-2 protein may interact in regulating the cell death process of activated memory lymphocytes and eliminating lymphocytes activated by viral infection.

Adult↗
PubMed1995

Progress in the management of patients with aneurysmal subarachnoid hemorrhage: a single hospital review for 20 years. Part I: Younger patients.

BACKGROUND: This study was carried out to clarify if there has been any improvement in the outcome of patients with aneurysmal subarachnoid hemorrhage during the past 20 years. Because elderly patients have apparently poorer prognoses than younger patients, patients older than 70 years were analyzed separately in the following article. METHODS: Five hundred seventy-one patients with aneurysmal subarachnoid hemorrhage, under 70 years, who were consecutively admitted to Kagawa Prefectural Central Hospital from July 1972 to December 1992, were reviewed. These patients were divided into four groups according to the time of admission. The ultimate outcome was evaluated by means of Glasgow Outcome Scale 6 months after the ictus. RESULTS: Changes in treatment protocol in this period included the induction of early surgery and the invention of a variety of modalities for the treatment of cerebral vasospasm. This resulted in a distinct increase in patients who actually underwent direct aneurysm clipping. Outcome has been significantly improved during this period, especially in patients with Hunt and Kosnik grade III (p<0.05, chi2). Patients in good clinical condition at follow-up (Glasgow Outcome Scale: good recovery) increased from 8.7% to 60.7%. Mortality decreased from 28.7% to 10.7%. CONCLUSIONS: Current therapeutic modalities have significantly improved the outcome of patients with aneurysmal subarachnoid hemorrhage. Rebleeding before early surgery remains as a major cause of unfavorable outcome and further progress on this subject is mandatory.

Aged↗
PubMed1995

Progress in the management of patients with aneurysmal subarachnoid hemorrhage: a single hospital review for 20 years. Part II: Aged patients.

BACKGROUND: We have reported improvement in the outcome of the younger patients with aneurysmal subarachnoid hemorrhage in the preceding article. The purpose of this article is to study if the same management protocol has simultaneously benefited the elderly patients. METHODS: One hundred twenty-nine patients with aneurysmal subarachnoid hemorrhage, over 70 years old, who were consecutively admitted to Kagawa Prefectural Central Hospital from July 1972 to December 1992, were reviewed. Patient grouping and outcome evaluation were the same as those of younger patients. RESULTS: Changes in treatment protocol in this period, which were similar to those of the younger counterparts, resulted in an increased number of patients who actually underwent aneurysm clipping. Although the outcome evaluated at 6 months after initial hemorrhage was significantly poorer than that of the younger counterparts, there have been some improvements during the study period. Patients in good clinical condition at 6 months' follow-up (Glasgow Outcome Scale: Good Recovery) increased from 37.5% to 42.9% in grades I-II and from 0% to 23.1% in grade III, respectively. CONCLUSIONS: The improvement in the outcome of elderly patients was less remarkable than that observed in younger patients. Significantly higher incidence of preoperative rebleeding and postoperative symptomatic vasospasm has proven to be the major cause of mortality and major morbidity at present. More careful and sophisticated perioperative care is required in elderly patients with aneurysmal subarachnoid hemorrhage.

Aged↗
PubMed1995

Successful treatment of an infant with veno-occlusive disease developed after allogeneic bone marrow transplantation by tissue plasminogen activator, heparin and prostaglandin E1.

A 15-month-old boy with severe aplastic anemia developed veno-occlusive disease (VOD) after allogeneic bone marrow transplantation (BMT), in which the preparative regimen included 50 mg/kg/day cyclophosphamide and anti-lymphocyte globulin for 4 consecutive days. The diagnosis was made based on clinical symptoms and data including, hepatomegaly, right upper quadrant abdominal pain, jaundice, ascites, coagulopathy and thrombocytopenia which was refractory to transfusions of platelet concentrate. We gave 2, 3, 5 and 5 mg/day/body of recombinant tissue plasminogen activator (tPA) followed by heparin and prostaglandin E1 (PGE1) effectively and without significant side effect on days 9, 10, 13 and 14, respectively. Clinical and biochemical improvement was steady and dramatic. We suggest that tPA following continuous heparin and PGE1 infusion may be useful in the treatment of VOD even in infantile cases.

Alprostadil↗
PubMed1995

Detection of human cytomegalovirus DNA in immunocompromised children by polymerase chain reaction.

BACKGROUND: Cytomegalovirus (CMV) infection is a major complication in immunocompromised patients, such as those with leukemia, acquired immunodeficiency syndrome (AIDS) and allograft recipients. A sensitive and specific diagnostic procedure of CMV infection is required. The polymerase chain reaction (PCR) procedure has been demonstrated to be more sensitive than conventional virus isolation. However, CMV DNA can be detected in patients with latent or asymptomatic infections by PCR because of its extreme sensitivity. OBJECTIVES: In this study, we used PCR and reverse transcription PCR (RT-PCR) to detect CMV DNA and mRNA in immunocompromised patients and evaluated the value of PCR and RT-PCR for diagnosis of active CMV infection. STUDY DESIGN: We examined thirty immunocompromised children for CMV DNA using peripheral blood mononuclear cells (PBMC), polymorphonuclear leukocytes (PMNL). urine and throat swabs from October 1991 to March 1992. Eighteen of the patients had acute lymphoblastic leukemia, four had non-Hodgkin's lymphoma, two had Wilms' tumor and six were recipients of an allogeneic bone marrow transplantation. Four patients developed CMV-related clinical symptoms during the observation period: two patients with pneumonia and two patients with hepatitis. RESULTS: CMV DNA was detected in four patients with clinical symptoms and in five patients without evidence of CMV infection. The incidence of CMV DNA was significantly higher in symptomatic patients than asymptomatic patients. CMV mRNA encoding the late antigen was detected by RT-PCR only in patients with clinical symptoms of CMV infection. CONCLUSIONS: We concluded that detection of CMV DNA by PCR is of little clinical significance for distinguishing latent form active CMV infection. It is suggested that detection of CMV mRNA by RT-PCR is useful for diagnosis of active CMV infection.

Journal Article↗
PubMed1995

Detection of varicella-zoster virus (VZV) DNA in throat swabs and peripheral blood mononuclear cells of immunocompromised patients with herpes zoster by polymerase chain reaction.

BACKGROUND: Varicella-zoster virus (VZV) is rarely isolated from throat swabs and peripheral blood leukocytes from patients with herpes zoster by conventional virus isolation methods. The polymerase chain reaction (PCR) is a highly sensitive method to detect VZV genomes. It has been reported that VZV DNA was detected in the cerebrospinal fluid (Puchhammerstockl et al., 1991) and peripheral blood mononuclear cells (PBMC) of patients with VZV-associated neurological symptoms (Gilden et al., 1992) by PCR. OBJECTIVES: We used the nested double PCR to detect VZV DNA in patients with herpes zoster. STUDY DESIGN: Sixteen patients with herpes zoster, ten immunocompromised and six immunocompetent patients, were studied. Throat swabs and PBMC were collected weekly and examined for VZV DNA by the nested double PCR. RESULTS: VZV DNA was detected in 60% (6/10) of throat swabs and in 60% (6/10) of PBMC of immunocompromised patients, and in 16.7% (1/6) of throat swabs and in 33% (2/6) of PBMC of immunocompetent patients within two weeks after the onset of skin rash. VZV DNA was detected in throat swabs or PBMC of two patients 5 and 7 days after cessation of acyclovir. CONCLUSION: VZV DNA was detected in throat swabs and PBMC-associated viremia exist in patients with herpes zoster. It is suggested that VZV spread from sensory ganglia to the skin or pharyngeal area along the nerve fiber or hematogenously and local cutaneous replication of VZV can lead to viremia with subsequent hematogenous dissemination in patients with herpes zoster.

Journal Article↗
PubMed1995

Markedly elevated levels of beta2-microglobulin in urine with measles viruria in patients with measles.

BACKGROUND: Measles is a highly contagious infectious disease in children. However, the pathogenesis has not yet been fully defined since susceptible cells to measles virus (MV) had not been developed. Recently, B95a cells, which are very susceptible to MV, have been reported. OBJECTIVES: To evaluate measles viruria in patients with measles, isolation of MV from urine was performed using B95a cells. STUDY DESIGN: Isolation of MV from supernates or sediments of urine in patients with measles was performed using B95a cells. The levels of beta2-microglobulin (MG) in urine and serum were also measured. RESULTS: MV was isolated from either supernates or sediments of urine. MV was isolated from 10 of 11 samples (91%) within 2 days of the appearance of a rash. MV was isolated from supernates of urine for up to 4 days after the appearance of a rash, and from sediments for up to 5 days. The levels of urinary beta2-MG were elevated within 2 days of the appearance of a rash. The levels of urinary beta2-MG with measles viruria were significantly higher compared to those without measles viruria. CONCLUSIONS: Measles viruria may occur early in all patients with measles and elevated levels of urinary beta2-MG in patients with measles may be the consequence of tubular injury.

Journal Article↗
PubMed1995

Paroxysmal supraventricular tachycardia initiated by ventricular couplets in concealed ventricular trigeminy.

A case report of a man with ventricular concealed trigeminy in whom ventricular couplets initiating paroxysmal supraventricular tachycardia were occasionally seen is reported. This is the first report on concealed trigeminy with couplets. This strengthens the authors' previous suggestion that supernormal conduction may occur in the reentrant pathway of extrasystoles, as a mechanism of ventricular couplets.

Cardiac Complexes, Premature↗
PubMed1995

Quality of portal verification images using GLP7 film.

RATIONALE AND OBJECTIVES: To improve portal verification radiographs, we tested the application of GLP7 film. METHODS: The quality of the portal verification radiograph using the XV cassette-GLP7 film combination and the XL cassette-GLP7 film combination was investigated. The XV cassette-XV2 film combination and the SA cassette-GS screen-XTL film combination also were used for comparison. RESULTS: The characteristic curves showed that the relative speeds were 0.32 and 0.47 for the XV-GLP7 and XL-GLP7 combinations and that the average gradients were 1.93, 2.14, and 1.32 for the XV-GLP7, XL-GLP7, and XV-XV2 combinations, respectively. In the experiment using Burger's phantom, the smallest visible volumes were 11.8, 11.3, 28.7, and 19.6 mm3 for the XV-GLP7, XL-GLP7, XV-XV2, and SA-GS-XTL combinations, respectively. In the lower dosage treatment in the clinic, there were no marked differences between the GLP7 film and XV2 film. However, in the higher dosage treatment, the GLP7 film had a better quality than did the XV2 film. CONCLUSION: Portal verification radiographs using GLP7 film are of sufficient quality for clinical use.

Humans↗