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Biomedical subjects

S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 109 records · Page 6Linked to original sources
PubMed2001

Role of lymphoid cells in age-related change of susceptibility to Friend leukemia virus-induced leukemia.

Susceptibility for Friend leukemia virus (FLV)-induced leukemogenesis was examined in the C3H/He (C3H)-->C57BL/6 (B6) radiation bone marrow chimeras of various age groups, and the effect of aging of host mice on the susceptibility was determined. The bone marrow chimera system provided the various age of FLV-resistant host mice (B6) possessing the same age of FLV-susceptible target cells from C3H mice. Using this system, we could determine the aging effect on the host resistancy against FLV without an influence of the aging effect on target cells. First, the young C3H-->young B6 chimeras and young C3H-->old B6 chimeras were compared. The young-->old chimeras were more susceptible to FLV-induced acute disease than the young-->young chimeras. The spleen CD4+ as well as CD8+ T cells were reduced in young-->old chimeras compared with young-->young chimeras. Similarly, the old C3H-->old B6 chimeras were more susceptible than old-->young chimeras and revealed the lower CD4+ T cell ratio in the spleen. Discussion was made on the possible implication of these findings on the role of T cells in age-related change of resistance to FLV-induced leukemogenesis.

Aging↗
PubMed2001

Affinity binding phenomena of DNA onto apatite crystals.

The effect of DNA on the crystal growth of hydroxyapatite (HAp) and its morphology was examined. X-ray diffraction patterns of DNA-containing apatites showed typical apatitic features. However, crystal growth was greatly inhibited in the presence of DNA during synthesis; particularly, the crystallinity in the a-axis direction decreased dramatically at low concentrations of DNA. The a- and c-axis dimensions of each precipitate were almost the same, which implies that DNA molecules affect only the crystal surface. CHN analysis clearly showed the presence of these elements, which increased with an increase in DNA concentration in the solution. Scanning electron micrographs of the precipitates formed in the presence of DNA showed typical needle-like crystals, with a decreased crystal size, especially width. Infrared absorption spectroscopy of the DNA-containing apatites showed that the 1630-1700 cm(-1) absorption band due to C=C and C=N stretching increased with an increase in DNA concentration during precipitation. The ESCA spectrum of HAp(DNA 1.0) shows N 1s and C 1s peaks that are absent and weak, respectively in HAp. 31P NMR spectroscopy revealed a weak peak at the base of the 31P peak from the PO4(3-) ions in the HAp crystals. This weak 31P peak had a small positive shift from the position found in native DNA which may be due to the phosphate backbone of adsorbed DNA. The apparent solubility of the HAps increased with an increase in DNA concentration. These results suggest that there is an affinity binding between apatite crystal and DNA molecules.

Animals↗
PubMed2001

The first case of 4-hydroxybutyric aciduria in Japan.

We report a boy with 4-hydroxybutyric aciduria resulting from a deficiency of succinic semialdehyde dehydrogenase (SSADH). A boy, 1 year 5 months, showed delayed walk with hypotonia and could not speak meaningful words. The blood levels of lactate, pyruvate and amino acids were not elevated. Head magnetic resonance imaging (MRI) and electroenchephalography (EEG) were normal. Urinary organic acid analysis with gas chromatography-mass spectrometry (GCMS) revealed increased levels of 4-hydroxybutyric acid, glutaric acid, adipic acid and suberic acid. The concentrations of 4-hydroxybutyric acid and gamma-aminobutyric acid (GABA) were elevated in the serum and cerebrospinal fluid (CSF). SSADH activity in cultured lymphoblasts was 4.5% of the normal level. So far as we know this is the first Japanese patient diagnosed as 4-hydroxybutyric acid. Urinary organic acid analysis is necessary for the diagnosis of patients with unexplained psychomotor retardation.

Aldehyde Oxidoreductases↗
PubMed2001

A variant case of congenital bilateral perisylvian syndrome with asymmetric findings on neuroimaging and septum pellucidum defect.

We report a 17-year-old female patient with a variant form of congenital bilateral perisylvian syndrome (CBPS). She had pseudobulbar palsy, partial epilepsy and mild pyramidal symptoms predominantly in the left hand. Magnetic resonance imaging revealed asymmetric perisylvian and perirolandic polymicrogyric cortical dysplasia and septum pellucidum defect. The clinicoradiological findings for this patient met the criteria for CBPS. Moreover, they appeared to overlap those of congenital unilateral perisylvian syndrome. The findings in this case support the hypothesis that these two syndromes are parts of a continuous spectrum of one clinico-radiological syndrome.

Adolescent↗
PubMed2001

A severely brain-damaged case of 3-hydroxyisobutyric aciduria.

We report a male case of 3-hydroxyisobutyric aciduria (3HiB-uria) with severe brain damage. He had mild asphyxia at birth. He needed tube feeding for a month. He showed mild dysmorphic features, including low set ears, a long philtrum and micrognathia. At 4 months of age he had acute encephalopathy. Thereafter, severe brain damage remained and mechanical ventilation care was needed all day. After he had been admitted to our hospital at 3 years of age, repeated organic acid analysis of urine confirmed the diagnosis of 3HiB-uria. This patient had been previously diagnosed as having cerebral palsy and sequelae of acute encephalopathy.

Acidosis↗
PubMed2001

AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity.

AS-924 is an oral prodrug of the antibiotic ceftizoxime (CTIZ), a parenteral use cephalosporin. This novel prodrug, produced by esterifying CTIZ with a lipophilic pivaloyloxymethyl (POM) group and introducing a water soluble L-alanyl group, is expected to increase the bioavailability and thereby, augment the antibacterial activity of CTIZ in vivo compared with existing prodrugs. To study the effect of the L-alanyl group in AS-924 on its bioavailability, the plasma concentration profiles of CTIZ in dogs were examined following the dosing of AS-924 and CTIZ-POM, in powder form, after pretreatment with the antacid ranitidine, and following the dosing of AS-924 after pretreatment with a gastrointestinal motility stimulant metoclopramide or suppressant scopolamine butylbromide. The absorption rate of AS-924 was constant under these different conditions due to its unique balance of lipophilicity and water solubility. CTIZ is as antibacterially active as pre-existing oral cephalosporins against Gram-positive clinical isolates, while being more active against all Gram-negative isolates-particularly Enterobacteriaceae and Haemophilus influenzae. A simulation model for the eradication profile of bacteria in computer programmed pharmacokinetic (PK) system was carried out to study the antibacterial action of CTIZ in human. CTIZ was proven to eradicate Streptococcus pneumoniae and H. influenzae effectively, while cefpodoxime (CPOD), the active moiety of CPOD proxetil, eradicated S. pneumoniae, but not H. influenzae. These results confirm that, AS-924 is a potent oral antibiotic and would be expected to be clinically effective and efficient.

Administration, Oral↗
PubMed2001

Pediatric caudal block with mepivacaine, bupivacaine or a mixture of both drugs: requirement for postoperative analgesia and plasma concentration of local anesthetics.

STUDY OBJECTIVES: To assess the effects of pediatric caudal block using mepivacaine, bupivacaine, or a mixture of both drugs on postoperative analgesia, and to examine plasma concentrations of the local anesthetics after caudal injection. DESIGN: Prospective, randomized, double-blind study. SETTING: Operating room and pediatric surgical ward. PATIENTS: 60 ASA physical status I children weighing 10 to 20 kg (26 females, 34 males), and scheduled for inguinal herniorrhaphy. INTERVENTIONS: Patients randomly received caudal block with 1 mL/kg of mepivacaine 1% (Group M, n = 20), 1 mL/kg of bupivacaine 0.25% (Group B, n = 20), or a mixture of 0.5 mL/kg of mepivacaine 1% and 0.5 mL/kg of bupivacaine 0.25% (Group MB, n = 20) after induction of anesthesia with sevoflurane in 50% oxygen (O2). Anesthesia was maintained with 66% nitrous oxide in O2 supplemented with sevoflurane at an end-tidal concentration of less than 1%. MEASUREMENTS AND MAIN RESULTS: Postoperative pain scores using a pediatric pain scale and plasma concentration of each local anesthetic were measured. In Group M, four patients required postoperative analgesics within the first 24 hours. However, no patients required postoperative analgesics in Groups B and MB. In Group M, the plasma concentration of mepivacaine of two patients exceeded 5 microg/kg of the level of toxicity. However, these patients did not show any toxic symptoms. Because a mixture of two local anesthetics halves the concentration of each local anesthetic, the plasma concentrations of mepivacaine and bupivacaine in Group MB were significantly lower than those of Groups M and B. CONCLUSIONS: Pediatric caudal block with a mixture of mepivacaine and bupivacaine is effective for intraoperative and postoperative analgesia.

Age Factors↗
PubMed2001

Electrophysiological correlates for response inhibition in a Go/NoGo task.

OBJECTIVE: Event-related brain potentials (ERPs) during a Go/NoGo task were investigated to elucidate the electrophysiological basis for executive and inhibitory control of responses. METHODS: We studied Go/NoGo ERPs in 13 healthy subjects during a modified continuous performance test using high-density electroencephalogram (EEG) recording. We measured peak latency, amplitude, and topographic distribution of the components, and analyzed the neural sources using low-resolution electromagnetic tomography. RESULTS: There were no differences between the Go and NoGo conditions in the latency, amplitude, scalp topography, or the electrical source localization of the P1 and N1 components. The N2 component was seen only in the NoGo ERP, and its source was located in the right lateral orbitofrontal and cingulate cortex. The NoGo-P3 component had larger amplitude and longer latency, and was more anteriorly localized than Go-P3; Go-P3 was located mainly in the medial part of the parietal cortex, whereas the NoGo-P3 activity was observed in the left lateral orbitofrontal cortex. CONCLUSIONS: These results suggest that the lateral orbitofrontal and anterior cingulate areas play critical roles in the inhibitory control of behavior and that both hemispheres are involved in inhibitory cognitive function.

Adult↗
PubMed2001

Action of protein-glutaminase on alpha-lactalbumin in the native and molten globule states.

The action of a novel protein-glutaminase from microorganisms on alpha-lactalbumin was investigated. When alpha-lactalbumin in the native state was incubated with protein-glutaminase, the deamidation proceeded gradually, i.e., the deamidation degree increased to 20% and 55% after 4 and 24 h, respectively. The transformation of alpha-lactalbumin from the native state to the molten globule state caused an increase in the rate of the enzyme-catalyzed deamidation, particularly in the early stage. The deamidation degree for the molten globule state reached 61% after 4 h, followed by a gradual increase to 66% after 24 h. CD spectral analyses of deamidated alpha-lactablumin revealed that the stability of the tertiary structure of alpha-lactablumin was closely related to the degree of deamidation, whereas the secondary structure was not affected by deamidation. Glutamine residues in alpha-lactalbumin to be modified by protein-glutaminase were identified as Gln[39], [43], [54], and [65]. Conformational characteristics of the amino acid sequence around these glutamine residues are discussed.

Amino Acid Sequence↗
PubMed2001

Therapeutic trial in the first three Asian cases of ethylmalonic encephalopathy: response to riboflavin.

Three Korean girls with ethylmalonic encephalopathy, the first Asian cases, were identified. In all three cases, we observed slight improvement in motor functions, cognitive behaviours and chronic mucoid diarrhoea after treatment with riboflavin and/or coenzyme Q10 treatment. The precise pathogenesis of ethylmalonic encephalopathy has not been fully elucidated, but riboflavin treatment may be helpful.

Brain Diseases, Metabolic, Inborn↗
PubMed2001

Synthesis and evaluation of various layered octacalcium phosphates by wet-chemical processing.

Octacalcium phosphate was synthesized by hydrolysis of alpha-tricalcium phosphate through a wet-chemical processing. Using the same wet-chemical processing in presence of various succinate ions, the preparation of some complexed octacalcium phosphates was attempted. The products were examined by X-ray diffraction method. These complexed octacalcium phosphates intercalated with succinic acid, L-asparatic acid, and methyl succinic acid showed an expanded basal spacing in the octacalcium phosphate unit cell dimensions. The microstructure was observed by scanning and transmission electron microscopy.

Journal Article↗
PubMed2001

A gene therapy model for retrovirus-induced disease with a viral env gene: expression-dependent resistance in immunosuppressed hosts.

At the initial stage of retroviral infection, virion envelope glycoprotein (env product) binds to cell surface receptors. Cells infected with retrovirus or into which the env gene was introduced, become resistant to superinfection by other retroviruses with the same receptor specificity, a phenomenon known as receptor interference. We have demonstrated previously that the introduction of an env gene from a truncated endogenous ecotropic murine leukemia virus (MuLV), the Fv-4 resistance (Fv-4r) gene, into the bone marrow hematopoietic cells of Fv-4 sensitive (Fv-4s) mice protected mice from ecotropic retrovirus-induced disease. Using the gene transfer system under the control of the retroviral vector and bone marrow transplantation (BMT), here we could show that the expression of an introduced Fv-4r gene in hematopoietic cells continued for more than 1 year after BMT. To determine the inhibitory mechanism of Fv-4r env gene expression against FLV-infection in this model system, peripheral blood mononuclear cells (PBMCs), or spleen cells from chimeras with various degrees of env-expression, were mixed with green fluorescence protein (GFP)-conjugated Friend MuLV envglycoprotein (GFP-Fr-ENV). The amount of GFP-Fr-ENV bound to these cells inversely correlated with the expression intensity of the transduced env gene indicating the receptor interference effect. Next, to see whether transduction of the Fv-4r gene would protect an immunosuppressed host from FLV-induced leukemogenesis, we generated immunocompromised chimeras by transplanting env-transduced bone marrow cells into a thymectomized host. These chimeras also resisted FLV-induced leukemogenesis, indicating that receptor interference-based gene therapy could become a therapeutic basis for immunodeficiency virus-induced diseases in vivo.

AIDS-Related Opportunistic Infections↗
PubMed2001

Distinct cell-specific expression patterns of early and late gibberellin biosynthetic genes during Arabidopsis seed germination.

Gibberellins (GAs) are biosynthesized through a complex pathway that involves several classes of enzymes. To predict sites of individual GA biosynthetic steps, we studied cell type-specific expression of genes encoding early and late GA biosynthetic enzymes in germinating Arabidopsis seeds. We showed that expression of two genes, AtGA3ox1 and AtGA3ox2, encoding GA 3-oxidase, which catalyzes the terminal biosynthetic step, was mainly localized in the cortex and endodermis of embryo axes in germinating seeds. Because another GA biosynthetic gene, AtKO1, coding for ent-kaurene oxidase, exhibited a similar cell-specific expression pattern, we predicted that the synthesis of bioactive GAs from ent-kaurene oxidation occurs in the same cell types during seed germination. We also showed that the cortical cells expand during germination, suggesting a spatial correlation between GA production and response. However, promoter activity of the AtCPS1 gene, responsible for the first committed step in GA biosynthesis, was detected exclusively in the embryo provasculature in germinating seeds. When the AtCPS1 cDNA was expressed only in the cortex and endodermis of non-germinating ga1-3 seeds (deficient in AtCPS1) using the AtGA3ox2 promoter, germination was not as resistant to a GA biosynthesis inhibitor as expression in the provasculature. These results suggest that the biosynthesis of GAs during seed germination takes place in two separate locations with the early step occurring in the provasculature and the later steps in the cortex and endodermis. This implies that intercellular transport of an intermediate of the GA biosynthetic pathway is required to produce bioactive GAs.

Arabidopsis↗
PubMed2001

Protein-glutaminase from Chryseobacterium proteolyticum, an enzyme that deamidates glutaminyl residues in proteins. Purification, characterization and gene cloning.

A novel protein-deamidating enzyme was purified to homogeneity from Chryseobacterium proteolyticum and the gene encoding it was cloned. The enzyme is a monomer with a pI of 10.0, a measured M(r) of approximately 20,000 and a calculated M(r) of 19,860. Extensive comparison with Streptoverticillium transglutaminase showed that the protein-deamidating enzyme lacked transglutaminase activity in terms of hydroxamate-formation between benzyloxycarbonyl-Gln-Gly and hydroxylamine, or monodansylcadaverine incorporation into casein. The enzyme deamidated the two glutaminyl residues in the oxidized insulin A chain and deamidated both casein and the oxidized insulin B chain with higher catalytic efficiencies (k(cat)/K(m)) than with short peptides. The enzyme was active against several proteins, including insoluble wheat gluten, but did not deamidate asparaginyl residues in peptides, free glutamine or other amides. The enzyme was therefore named protein-glutaminase (EC 3.5.1). The gene encoding the protein was cloned and, when expressed in Escherichia coli, the protein product had protein-glutaminase activity and cross-reacted with antiserum raised against the purified enzyme. The protein-glutaminase was shown to be expressed as a prepro-protein with a putative signal peptide of 21 amino acids and a pro-sequence of 114 amino acids. The amino-acid sequence had no obvious homology to any published sequence and is therefore a novel protein-glutaminase.

Amidohydrolases↗
PubMed2001

Cytoplasmic surface structure of bacteriorhodopsin consisting of interhelical loops and C-terminal alpha helix, modified by a variety of environmental factors as studied by (13)C-NMR.

We have examined the (13)C-NMR spectra of [3-(13)C] Ala-labeled bacteriorhodopsin and its mutants by varying a variety of environmental or intrinsic factors such as ionic strength, temperature, pH, truncation of the C-terminal alpha helix, and site-directed mutation at cytoplasmic loops, in order to gain insight into a plausible surface structure arising from the C-terminal alpha helix and loops. It is found that the surface structure can be characterized as a complex stabilized by salt bridges or metal-mediated linkages among charged side chains. The surface complex in bacteriorhodopsin is most pronounced under the conditions of 10 mM NaCl at neutral pH but is destabilized to yield relaxed states when environmental factors are changed to high ionic strength, low pH and higher temperature. These two states were readily distinguished by associated spectral changes, including suppressed (cross polarization-magic angle spinning NMR) or displaced (upfield) (13)C signals from the C-terminal alpha helix, or modified spectral features in the loop region. It is also noteworthy that such spectral changes, when going from the complexed to relaxed states, occur either when the C-terminal alpha helix is deleted or site-directed mutations were introduced at a cytoplasmic loop. These observations clearly emphasize that organization of the cytoplasmic surface complex is important in the stabilization of the three-dimensional structure at ambient temperature, and subsequently plays an essential role in biological functions.

Amino Acid Sequence↗
PubMed2001

Cognitive function and frontal lobe atrophy in normal elderly adults: Implications for dementia not as aging-related disorders and the reserve hypothesis.

We examined the relations between cognitive function and age and education in the normal elderly population. As per the community-based stroke, dementia, and bed confinement prevention in the town of Tajiri, neuropsychological assessments, including the Cognitive Ability Screening Instrument (CASI), were performed for 99 randomly selected normal elderly subjects. We assessed the frontal function (working memory, word fluency, Trail-Making Tests, CASI subitems of list-generating fluency, attention, and concentration/mental manipulation), language function (proverbs, CASI subitem language), non-language function (the digit symbol test of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), CASI subitem visual construction), memory (Alzheimer's Disease Assessment Scale recall/recognition, story recall, CASI subitems short and long-term memory, the Rey-Osterrieth Complex Figure Test), and the global function (CASI subitems orientation and abstraction and judgment). We found that the only test affected by age was the digit symbol test of the WAIS-R. The effects of education were distributed among various tests. There was a significant correlation between age and the frontal lobe atrophy in the lower educated group. The present findings suggest that cognitive function is spared by the aging process itself and dementia should be considered as age-related, not aging-related disorders, and that education might have a protective effect on cognitive change, supporting the reserve hypothesis.

Age Factors↗