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Biomedical subjects

S Sakuragi

Publications and source records attributed to S Sakuragi.

At least 37 records · Page 2Linked to original sources

Uniquely abnormal intracavitary flow during late systole and relaxation in hypertrophic obstructive cardiomyopathy with midventricular obstruction.

We describe a patient with hypertrophic cardiomyopathy who had a uniquely abnormal jet from the base to the apex during late systole and the relaxation period. This 48-year-old woman was admitted with exertional dyspnea and palpitations. Two-dimensional echocardiography revealed asymmetric septal hypertrophy and a left midventricular obstruction at the level of the papillary muscles. A high-velocity ejectional jet (peak velocity 4.8 m/s) directed toward the base during systole and an abnormal jet (peak velocity 2.2 m/s) directed toward the apex during late systole and the relaxation period were demonstrated through the midventricular obstruction site using Doppler echocardiography. The peak systolic pressure gradient between the apical and the basal chamber was 91 mmHg, and the peak systole pressure was higher in the apical chamber than in the basal chamber. However, a reverse pressure gradient was revealed between the two chambers during late systole and the relaxation period when the abnormal jet was demonstrated.

Cardiomyopathy, Hypertrophic↗

Functional analysis of simian immunodeficiency virus SIVAGM long terminal repeat.

We have previously shown that long terminal repeats (LTRs) derived from various isolates of SIVAGM share a unique functional property. In the absence of viral Tat, all SIVAGM LTRs act as much more efficient promoters than any of the other LTRs derived from representative primate immunodeficiency viruses. In the presence of Tat, however, SIVAGM LTRs are activated relatively inefficiently. To map the elements that confer these features on the SIVAGM LTR, a number of deletion mutants were constructed, and their promoter activities were determined using a bacterial CAT gene as a marker. The results obtained indicated that various elements located in the U3 region may contribute to the high basal promoter activity and that no negative elements are present in the region. The Tat-responsive sequence TAR was localized to the R region as observed for the other LTRs. A mutant carrying a single nucleotide deletion in this region completely lost responsiveness to Tat protein.

Base Sequence↗

Lectin cytochemical analysis of glycoconjugates in photoreceptor cell membranes of Lampetra japonica.

Seven types of ferritinized lectin were used to examine the distribution of glycoconjugates on the outer segment membranes of lamprey photoreceptor cells. Ultrastructural pre-embedding labeling revealed that peanut agglutinin, soybean agglutinin and Ricinus communis agglutinin I were preferentially bound to the proximal, lateral and luminal surfaces of the long cell outer segments, whereas Griffonia simplicifolia agglutinin II and concanavalin A agglutinin were bound to the corresponding surfaces of the short cell outer segments. The results indicate that there is marked difference in the composition of glycoconjugates over the outer segment membranes between long and short photoreceptors.

Animals↗

pH-dependent changes in interphotoreceptor matrix domains surrounding cone photoreceptors.

The cone matrix sheath is a biochemically and structurally distinct domain of the retinal interphotoreceptor matrix (IPM). In the present study, the insoluble components of the cone matrix sheath were extracted from bovine retina, and examined for pH-dependent morphological changes by light and electron microscopy. After soaking unfixed retinas in 25 mM HEPES-buffered solution (pH 2.0), sheets of aqueous-insoluble IPM containing cone matrix sheaths were physically dissociated from the inner retina. The insoluble IPM preparations were treated with 1.0% Triton X-100 to extract contaminating photoreceptor outer segment membrane, and exposed to HEPES-buffered solutions at pH 2.0, 4.5, 7.0, or 9.5. The cone matrix sheath, specifically stained with peanut agglutinin, appeared finely granular at pH 2.0, but was markedly condensed at pH 4.5. Cone sheath morphology became dispersed and appeared as a network of thick fibrils at pH 7.0, and further dispersed fibrillar and granular elements at pH 9.5. These findings suggest that pH changes in the interphotoreceptor space can alter the molecular organization of the IPM and influence the function of the IPM in the transport of nutrients and metabolites, and in retinal adhesion.

Animals↗

Effects of adenosine triphosphate on wide QRS tachycardia. Analysis in 18 patients.

A few studies have indicated that adenosine terminated triggered-activity idiopathic ventricular tachycardia, but all involved a small number of cases. The effects of adenosine triphosphate (ATP) on wide QRS tachycardia have thus not yet been completely clarified. This retrospective study was performed to evaluate the therapeutic and diagnostic utility of ATP in wide QRS tachycardia. A total of 18 patients with wide QRS tachycardia (QRS width > 120 msec, rate > or = 150 beats/min) were evaluated. ATP, 20-40 mg, was administered intravenously. An electrophysiological study and treadmill stress test were performed in all patients to elucidate the mechanism of the tachycardia. ATP terminated tachycardia or induced atrio-ventricular block in all 6 patients who had supraventricular tachycardia, but it had no effect on preexcited atrial fibrillation or pre-excited atrial flutter. Ventricular tachycardia was terminated by ATP in 5 of the 10 patients. In 4 of these 5 patients, the focus of the tachycardia was the right ventricular outflow tract. No entrainment phenomenon was demonstrated by electrophysiological study with induction of the tachycardia by stress test or isoproterenol infusion, suggesting the contribution of triggered activity to the tachycardia. In the remaining patient with complete right bundle branch block type tachycardia with right axis deviation, the mechanism of ventricular tachycardia could not be determined. In the 5 patients in whom ATP failed to terminate ventricular tachycardia, the reentry mechanism was suggested by the presence of entrainment phenomenon depicted on electrophysiological study. In summary, this study suggests that ATP terminates supraventricular wide QRS tachycardia and ventricular tachycardia due to triggered-activity, but that it has no effect on pre-excited atrial fibrillation or flutter or on ventricular tachycardia due to a reentry mechanism. These findings add to the mounting evidence regarding the therapeutic and diagnostic utility of ATP in wide QRS tachycardia.

Adenosine Triphosphate↗

[Two cases of malignant lymphoma with initial symptoms like orbital cellulitis and complicated by hemophagocytosis].

We reported 2 patients with malignant lymphoma complicated by hemophagocytic syndrome. Their clinical signs at onset were those of orbital cellulitis. Lymphoma complicated with hemophagocytosis is called lymphoma-associated hemophagocytosis syndrome (LAHS) and its prognosis is reported to be very poor. So far as we know, this is the first report in the ophthalmological field. In our patients, we suspected that the lesions occurred from the orbit or skin of this area. The first patient was a 22-year-old man and the second patient a 16-year-old girl. The diagnosis was very difficult at the onset of disease. Within 6 months after the first opthalmological examination, both died. When orbital cellulitis is suspected and antibiotic therapy is ineffective, we should suspect hemophagocytic syndrome (HPS) and should examine serum ferritin which is a good markers of HPS. Early biopsy and consultation with a hematologist are very important.

Adolescent↗

[Suppression of experimental autoimmune uveitis by energy restriction].

The effects of energy restriction on experimental autoimmune uveitis (EAU) were investigated. Seven-week-old, male Lewis rats were divided into three groups. Experiment A) A control group was fed ad libitum, a second group was given 50% calorie restricted food from the day of immunization, and a third group was given 50% calorie restricted food from 2 weeks before immunization. Experiment B) A control group was fed ad libitum, a second group was given 25% calorie restricted food from 4 weeks before immunization, and a third group was given 50% calorie restricted food 4 weeks before immunization. All rats were immunized with interphotoreceptor retinoid-binding protein (IRBP). In experiment A), in the group given 50% calorie restricted food from 2 weeks before immunization, and in experiment B), in the group given 50% calorie restricted food from 4 weeks before immunization, the onset of EAU was significantly delayed, the clinical symptoms were lessened, and delayed hypersensitivity against IRBP was suppressed. Clinically and histologically, the severity was also low. In the group given 50% calorie restricted food from 4 weeks before immunization, the titer of anti-IRBP antibody was also significantly lower than in the control group.

Animals↗

Progressive zonal outer retinitis.

A 27-year-old woman with uniocular progressive zonal outer retinitis was examined. The retinitis area was curvilinear and gray, with zonal opacification. It enlarged centrifugally and concentrically, with narrowing of the zonal opacification. Results of perimetry and electroretinography showed that the outer retina was primarily affected. Damage was more severe in the photoreceptor cones than in the rods. Peripheral retinal phlebitis was seen on fluorescein angiography. Intraretinal pigment migration with retinal pigment epithelial atrophy occurred in the macula as sequelae.

Adult↗

Both SU and TM env proteins are responsible for monkey cell tropism of simian immunodeficiency virus SIV mac.

While simian immunodeficiency virus (SIV) derived from an infectious molecular clone pMA239 is tropic and pathogenic for monkeys, the virus derived from another infectious clone pMA142 does not replicate in monkey cells. To determine genetic sequences responsible for this tropism, a series of recombinant clones were constructed from pMA142 and pMA239. The determinant in pMA239 was mapped within regions encompassing the env gene. Viruses, which carry the 239 env gene encoding surface and/or transmembrane proteins, were tropic for monkey cells.

Animals↗

The looping behavior of fish in microgravity.

Fish subjected to microgravity during space flight were monitored for their swimming behavior, particularly the looping response. Experiments were performed on normal fish, unilaterally labyrinthectomized fish, and bilaterally labyrinthectomized fish. Observation were compared against the behavior of other species which had been evaluated in microgravity during parabolic flight.

Animals↗

Clinical characteristics of hepatitis C virus-associated retinopathy.

The morbidity rate for retinopathy of unknown origin was significantly higher (P < 0.001) in the chronic hepatitis C group, 27 (31.8%) of 85 cases, than in the control group, 6 (6.0%) of 100 cases. Among hepatitis C virus (HCV)-associated retinopathy patients, 6 cases (22.2%) were aware of ocular subjective symptoms, retinopathy recurred in 8 (29.6%) cases, binocular retinopathy occurred in 14 (51.9%) cases, and retinopathy related to liver dysfunction, in 13 (81.3%) of 16 tested cases. HCV-associated retinopathy involved hemorrhage at the posterior pole retina in 21 (77.8%), cotton-wool patches in 9 (33.3%), and hemorrhage at the peripheral retina in 7 (25.9%) cases. Sequelae occurred in only one case. Retinopathy worsened or recurred in all 7 cases treated with interferon. The risk factors for HCV-associated retinopathy were mild thrombocytopenia (P < 0.001), long-term hepatitis illness (P < 0.005), advanced age (P < 0.02), concurrence with liver cirrhosis (P < 0.02), history of systemic hypertension (P < 0.05), and female gender (P < 0.05).

Adult↗

[Analysis of the candidate antigen for Harada's disease].

The candidate antigen for Vogt-Koyanagi-Harada's (VKH) disease was isolated from cultured human melanoma cells (G-361). First, the soluble protein from the melanoma cells was separated into several fractions according to the molecular weight by gel filtration. In each fraction, the antigenicity was analysed by lymphocyte proliferation assay using peripheral blood lymphocytes (PBLs) from VKH disease patients. Then the positive fractions were further separated by liquid isoelectrofocusing followed by SDS polyacrylamide gel electrophoresis. In the liquid isoelectrofocusing fractions, the fraction at about pH 6.0 contained the antigenic protein. The protein from the 75 kDa band on the SDS-PAGE of this fraction was able to cause proliferation of the PBLs from the VKH disease patients. Thus, it appears that the 75 kDa protein of pH 6.0 isoelectrofocusing point was the specific autoimmune antigen for VKH disease.

Adult↗

Compatibility of Tat and Rev transactivators in the primate lentiviruses.

Primate immunodeficiency viruses carry a unique set of transacting regulator genes, which are essential for viral replication. The exchangeability of these Tat and Rev transactivators derived from viruses of the four major subgroups identified to date was assessed in transient transfection and infection assay systems. The human immunodeficiency virus type 1 (HIV-1), a major causative virus of human AIDS, efficiently activated the other viruses. In contrast, the tat and rev gene products of HIV-2, SIVAGM (virus of the African green monkey), and SIVMND (virus of the mandrill) did not fully transactivate the HIV-1. In particular, the rev of HIV-1 was not substantially replaced by those of the other viruses. The result that HIV-1 is distinct from the other immunodeficiency viruses with respect to the compatibility of two transactivators gives a firm functional basis for the unique phylogenetic position of HIV-1.

Amino Acid Sequence↗

Integration is essential for efficient gene expression of human immunodeficiency virus type 1.

A mutant of human immunodeficiency virus type 1 which carries a frameshift insertion in the integrase/endonuclease region of pol gene was constructed in vitro. Upon transfection into cells, although this mutant exhibited a normal phenotype with respect to expression of gag, pol, and env genes and to generation of progeny virions, no replication-competent virus in CD4-positive cells emerged. An assay for the single-step replication of a defective viral genome dependent on trans complementation by rev protein was established and used to monitor the early phase of viral infection process. Viral clones with a mutation in the vif, vpr, or vpu gene displayed no abnormality in the early phase. In contrast, the integrase mutant did not direct a marker gene expression after infection. Together with an observation that the mutant lacked the ability to integrate, these results indicated that the integration was required for efficient viral gene expression and productive infection of human immunodeficiency virus type 1.

Cell Line↗

Cell-dependent requirement of human immunodeficiency virus type 1 Vif protein for maturation of virus particles.

A highly sensitive single-round infection assay using a bacterial chloramphenicol acetyltransferase was developed to analyze an early stage of human immunodeficiency virus type 1 replication. By a combination of transfection and single-round infection assay, a virus with a vif mutation, depending on host cells from which the virus was derived, was demonstrated to be defective at the early phase of infection cycle. Analysis of viral proteins synthesized in cells indicated that incorporation of the Env surface protein into virions of the vif mutant, again in a cell-dependent way, was greatly restricted. Taken together, it is concluded that the Vif protein acts through modulation of the Env protein in the virions, directly or indirectly, to enhance viral infectivity in a certain cell type.

Acquired Immunodeficiency Syndrome↗

Genetic characterization of simian immunodeficiency virus isolated from an African mandrill.

We constructed an infectious molecular clone of simian immunodeficiency virus from an African mandrill (SIVMND). Upon transfection, this clone directed the production of progeny virus particles infectious to and cytopathic for CD4+ human leukemia cells. Thirteen frameshift proviral mutants with an alteration in the eight open reading frames of SIVMND were generated by recombinant DNA techniques, and were analyzed biologically and biochemically. While mutations in the structural genes gag, pol, and env abolished viral growth and induction of cytopathology, mutants of the vif, vpr, and nef genes were fully biologically active. Of the tat and rev mutants, only one rev mutant grew in CD4+ cells with delayed kinetics. In reporter-based transient expression systems, transactivation potentials of the tat and rev mutants were evaluated. A mutant lacking 2nd coding exon of tat gene exhibited tat activity similar to that of the wild type clone. The infectious rev mutant was partially defective for rev gene activity.

Amino Acid Sequence↗

Functional analysis of biologically distinct genetic variants of simian immunodeficiency virus isolated from a mandrill.

We examined the biological properties of two infectious clones of a simian immunodeficiency virus, SIVMND, which were designated as pMD121 and pMD122. Upon transfection into CD4-negative cells, pMD122 generated virions much less efficiently than pMD121. Likewise, the growth kinetics in CD4-positive cells of virus derived from pMD122 were remarkably delayed relative to those of virus from pMD121. The cytocidal activity of the MD122 virus was also low. A series of recombinant clones were constructed from pMD121 and pMD122 to determine the sequence responsible for the low virulence of the MD122 virus. The genetic determinant in pMD122 responsible for its properties was mapped to within a region (316 base pairs) encompassing the tat, rev, and env coding sequences. Sequence analysis revealed that the two clones differed by only one nucleotide in this region. A nucleotide substitution G (pMD121) to T (pMD122) altered an arginine codon to a serine codon in the first tat coding exon. Transient transfection experiments showed that the tat activity of pMD122 was about twofold less than that of pMD121. These findings indicate that small differences in tat activity can have a dramatic effect on the biological behavior of SIVMND.

Amino Acid Sequence↗

Functional classification of simian immunodeficiency virus isolated from a chimpanzee by transactivators.

In reporter-based transient expression systems, we characterized simian immunodeficiency virus from a chimpanzee (SIVCPZ), with special reference to the human immunodeficiency virus type 1 (HIV-1). SIVCPZ was not equally activated by tat and rev transactivators derived from representative primate lentiviruses. HIV-1 alone activated SIVCPZ to the full extent in both tat and rev assays. The tat and rev gene products of SIVCPZ, as well as those of HIV-1, efficiently transactivated the other viruses. These results indicate that SIVCPZ is identical to HIV-1 with regard to the compatibility of tat and rev gene activities among four subgroups of primate lentiviruses.

Amino Acid Sequence↗