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Biomedical subjects

R Shibata

Publications and source records attributed to R Shibata.

At least 73 records · Page 4Linked to original sources
PubMed1994

Persistent infection with SIVmac chimeric virus having tat, rev, vpu, env and nef of HIV type 1 in macaque monkeys.

A chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu, env, and nef genes of human immunodeficiency virus type 1 was generated. The chimeric virus, NM-3n, grew competently in peripheral blood mononuclear cells from cynomolgus monkeys like the parental SIVmac. Two cynomolgus monkeys and one rhesus monkey inoculated with NM-3n raised antibodies to SIVmac Gag and HIV-1 Env. The antibodies raised in the cynomolgus monkeys persisted for at least 1.7 years. The antibodies contained virus neutralizing activity not only to the original chimeric virus but also to the parental HIV-1. Infectious viruses were isolated from one of the cynomolgus monkeys 37 and 63 weeks after inoculation and from the rhesus monkey continuously from 6 weeks after infection onward. The recovered virus maintained its chimeric structure but included several clones with mutations in the env V3 region. When the recovered virus was inoculated to another rhesus monkey, no difference in the frequency of virus recovery was seen from the originally infected monkeys. These carrier monkeys have so far shown no sign of the disease.

Animals↗
PubMed1994

Second-site long terminal repeat (LTR) revertants of replication-defective human immunodeficiency virus: effects of revertant TATA box motifs on virus infectivity, LTR-directed expression, in vitro RNA synthesis, and binding of basal transcription factors TFIID and TFIIA.

Second-site revertants from replication-incompetent molecular clones of human immunodeficiency virus (HIV) contain base substitutions adjacent to the TATA motif. The altered TATA box motifs were analyzed for their effect(s) on virus infectivity, long terminal repeat (LTR)-directed expression in transient transfection assays, in vitro RNA synthesis, and assembly of the TFIID-TFIIA preinitiation complex. The revertant TATA boxes accelerated the kinetics of HIV replication when present in the context of an LTR containing a Sp1 mutation (deletion or site specific); no effect was observed on the infectivity of wild-type HIV. In chloramphenicol acetyltransferase assays and in vitro transcription systems, the altered TATA box motifs led to elevated basal levels of RNA synthesis from NF-kappa B- and Sp1-mutagenized and wild-type templates, respectively, but did not increase responsiveness to Tat transactivation. The revertant TATA boxes accelerated the binding of TFIID and TFIIA to the LTR and stabilized their association with the promoter. The revertants did not assemble a more-processive elongation complex. These results suggest that in the context of an impaired enhancer/promoter (viz., three mutated Sp1 elements), a series of HIV revertants emerge which contain LTR alterations that significantly augment basal RNA synthesis. The TATA motif revertants are capable of rescuing the enhancer/promoter defect and sustain virus infectivity.

Base Sequence↗
PubMed1994

Effect of tonsillectomy on peripheral blood T cell surface markers and cytokine production in patients with IgA nephropathy accompanied by chronic tonsillitis.

The present study investigated changes in peripheral blood T cell surface markers and cytokines (interleukin-2, IL-2; tumor necrosis factor-alpha, TNF-alpha; and interferon-gamma, IFN-gamma) following tonsillectomy in patients with IgA nephropathy accompanied by chronic tonsillitis. Peripheral blood CD8+ cells, CD45RA+CD4+ cells and CD8+CD11b- cells increased significantly after tonsillectomy, compared with their preoperative values. In some cases, the preoperative serum TNF-alpha and IFN-gamma levels were higher than normal before surgery, but decreased after surgery. These results suggest that tonsillectomy suppresses a decrease in suppressor T cells in patients with IgA nephropathy and corrects abnormal cell-mediated immune responses in these patients.

Adult↗
PubMed1994

Basilar artery migraine. Reversible ischemia demonstrated by Tc-99m HMPAO brain SPECT.

The authors present a case of basilar artery migraine in a 33-year-old woman who was initially misdiagnosed as having a cerebrovascular or mental disorder and subjected to MRI and cerebral angiography, which, however, did not show any pathologic findings. During admission to the university hospital, she lost consciousness. An emergency Tc-99m HMPAO brain SPECT showed a significant decrease of regional cerebral blood flow in the right temporal and occipital cortices, and right cerebellar hemisphere, where regional cerebral blood flow was decreased by 10-24% as compared to the left side. The second brain SPECT during a symptom-free phase showed the reversion of regional cerebral blood flow to normal in these areas. Basilar artery migraine was diagnosed by the finding of reversible ischemia in the territory of the right basilar artery on brain SPECT images and the clinical picture.

Adult↗
PubMed1993

Immunization of institutionalized asthmatic children and patients with psychomotor retardation using live attenuated cold-adapted reassortment influenza A H1N1, H3N2 and B vaccines.

Live attenuated cold-adapted reassortant (CR) influenza virus vaccines were evaluated in institutionalized asthmatic children and severe psychomotor-retarded (SPR) patients. Almost all the vaccinees were seropositive to the vaccine strains before immunization. Trivalent CR vaccine (containing A H1N1 (CR-125), A H3N2 (CR-149) and B (CRB-117)), bivalent CR vaccine (CR-125 and CR-149) and monovalent CRB-117 were inoculated to 19 asthmatic children and 36 and 16 SPR patients, respectively. Overall 49, 22, and 11% of vaccinees were infected by A H1N1, A H3N2 or B vaccine viruses, respectively, as indicated by significant haemagglutination-inhibition (HI) antibody titre rises 4 weeks after inoculation. No severe adverse reactions associated with CR vaccination were observed in the handicapped patients. A nosocomial outbreak of influenza A H1N1 occurred in the ward with asthmatic children, but none of the 19 CR-trivalent vaccinees became infected. However, five of 20 non-vaccinees in the same ward, and ten of 30 vaccinees in another ward that received inactivated split vaccine became infected. The CR vaccines demonstrated significant protective effects against natural exposure to the A H1N1 virus, and were well tolerated and safe when given to patients with bronchial asthma and severe psychomotor retardation.

Adolescent↗
PubMed1993

Trivalent cold recombinant influenza live vaccine in institutionalized children with bronchial asthma and patients with psychomotor retardation.

Twenty asthmatic children and 48 patients with severe psychomotor retardation were inoculated intranasally with trivalent cold-adapted recombinant (CR) influenza vaccine containing CR-125 (H1N1), CR-159 (H3N2) and CRB-117 (B). The vaccinees were mostly seropositive. Severe adverse reactions or asthmatic attacks were not observed, but 7 (15%) of 48 vaccinees with severe psychomotor retardation developed mild to moderate fever. Significant antibody responses in hemagglutination-inhibition tests were demonstrated in 33 (49%) vaccinees to CR-125, 20 (29%) to CR-159 and 8 (12%) to CRB-117. Two nosocomial outbreaks of influenza were observed in the subsequent winter. During an outbreak with H3N2 in one ward of severe psychomotor retardation patients, 2 (11%) of 18 vaccinees became infected compared with 10 (48%) of 21 placebo controls in the same ward (P < 0.05). In the other outbreak, with influenza B virus, 2 (14%) of 14 vaccinees and 13 (52%) of 25 controls in the ward for asthmatic children were infected (P < 0.05). The results indicate that trivalent CR vaccine is safe and effective against nosocomial outbreaks of influenza.

Adolescent↗
PubMed1993

Changes in local cerebral glucose utilization and dopamine metabolism in the rat brain following acute administration of haloperidol.

The effects of acute administration of haloperidol on local cerebral glucose utilization (LCGU) in 26 discrete regions of the rat brain were examined by the quantitative autoradiographic [14C] 2-deoxy-D-glucose technique and compared with the changes in dopamine (DA) metabolism in 13 brain regions examined by a high performance liquid chromatographic assay. A moderate dose (0.25 mg/kg) of acute haloperidol significantly reduced LCGU in a few brain regions; a high dose (1.0 mg/kg) reduced LCGU in 11 regions including the prefrontal cortex, thalamus and other subcortical structures, but not in the caudate putamen or accumbens nucleus. However, the levels of DA metabolite in the caudate-putamen, accumbens nucleus, prefrontal cortex, and medial thalamus were strikingly elevated with both doses of haloperidol. Thus, the changes in LCGU did not parallel presynaptic DA metabolism in terms of direction or distribution, and they might represent mainly the activities of postsynaptic sites.

Animals↗
PubMed1993

Differential effects of tight and loose 2-hour restraint stress on extracellular concentrations of dopamine in nucleus accumbens and anteromedial frontal cortex.

Changes in the extracellular dopamine (DA) concentrations were examined in the nucleus accumbens (NAS) and anteromedial frontal cortex (AMFCx) during either 2-hr loose or tight restraint stress by means of a microdialysis method. Loose restraint induced significant 100% and 30% increases in DA release in the AMFCx and NAS, respectively, and the increased DA levels returned to the control values despite continued stress. Tight restraint induced an almost constant 100-130% increase during stressing in the AMFCx and a 30% reduction in the NAS. Transient increases in DA release were observed in both regions soon after the cessation of loose, but not tight, restraint.

Animals↗
PubMed1993

Complete remission of neuroleptic-induced Meige's syndrome by botulinum toxin treatment: a case report.

A botulinum A toxin injection has beneficial effects on patients suffering from facial and cervical spastic disorders. However, its effect almost completely disappears within three months. We have reported a case of a 23-year-old schizophrenic patient with severe neuroleptic-induced Meige's syndrome in whom botulinum toxin treatment exerted a marked effect which lasted more than 15 months after the final injection of botulinum toxin in spite of continuous neuroleptic medication. It is concluded that botulinum can be recommended as a treatment of choice in neuroleptic-induced Meige's syndrome.

Adult↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

[A case of Down syndrome with chronic renal failure caused by long-term asymptomatic hyperuricemia].

The elevation of serum urate levels in patients with Down syndrome has been reported by several investigators, but gout or renal dysfunction due to hyperuricemia has rarely been encountered. We described a case of Down syndrome showing chronic renal failure caused by long-term asymptomatic hyperuricemia. A 30-year-old man, who had persistent subclinical hyperuricemia for nine years, was noted to have pale face, weakness and hypertension. Laboratory findings revealed acute renal dysfunction. He died from uremic lung 7 months later. Autopsy disclosed a finding suggesting chronic urate nephropathy; many gouty microtophi with foreign body reaction in the renal medulla. It is important to estimate serum urate and to control increased serum urate level in order to prevent from renal dysfunction in Down syndrome.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

SIV/HIV recombinants and their use in studying biological properties.

A series of chimeric clones between human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses (SIV) were constructed. Viability of the recombinant viruses was dependent on the position of recombination. Infectious chimeric viruses between HIV-1 and SIVAGM (isolated from an African green monkey) and those between HIV-1 and SIVMAC (isolated from a rhesus monkey) were examined for host cell tropism. Viral determinants that restrict the replication of SIVAGM in human MT-4 cells and that of HIV-1 in macaque monkey peripheral blood mononuclear cells (PBMC) mapped to the 5' half of the virus genome. One HIV-1/SIVMAC chimera which contained the HIV-1 env gene was shown to replicate in macaque PBMC in vitro and to infect macaque monkeys in vivo. This HIV-1/SIVMAC chimera will be useful for a variety of AIDS pathogenesis and vaccine studies.

Animals↗
PubMed1992

Pharyngoconjunctival fever caused by adenovirus type 11.

Among a group of hospitalized children in Fukuoka, southern Japan, an epidemic of pharyngoconjunctival fever-like disease caused by adenovirus type 11 was observed in the autumn of 1988. Of the 47 children studied 38 were seronegative in neutralizing antibody for adenovirus type 11 before the epidemic, and seroconversion occurred in 16 (42%) including 5 subclinical cases. Of the 11 symptomatic patients the incidences of conjunctivitis, pharyngitis and fever were 91, 64 and 46%, respectively. Four patients (36%) had all three symptoms. Fifteen patients (94%) were boys. The sex predominance and high incidence of conjunctivitis suggested that infection may have been transmitted in the large bathroom where boys took baths together.

Adenovirus Infections, Human↗