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Biomedical subjects

I Kato

Publications and source records attributed to I Kato.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (2)--Single oral dose toxicity study in dogs].

Cefmatilen hydrochloride hydrate (S-1090) was administered at 500 and 1000 mg potency/kg once orally to beagle dogs. No deaths occurred. Vomiting, diarrhea or mucous feces occurred on the dosing day, and reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) were also observed on the dosing and next day. Increases of plasma urea nitrogen and iron were observed on the next day after dosing. No remarkable changes were noted in other examination items. The animals in both groups were considered to be exposed to a similar level of S-1090 based on the toxicokinetic data. The oral lethal dose of S-1090 in dogs was estimated to be more than 1000 mg potency/kg.

Administration, Oral↗
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (5)--Six-month repeated oral dose toxicity study and supplement study in rats].

Cefmatilen hydrochloride hydrate (S-1090) was orally administered to rats at dose levels of 100, 300 and 1000 mg potency/kg once daily for 6 months. All the S-1090 treated groups showed soft feces, reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet), abdominal distention, increased food and water consumption, lower urine pH, and a decrease of white blood cells counts (except for males of the 100 mg potency/kg group). One male in the 300 mg potency/kg group showed mucous feces and marked decrease in body weight, and diet in the middle stage of the administration period. In necropsy of the survivors of all treated groups, marked cecal enlargement was noted. No remarkable changes were observed in the other examination items. From the early stage of the withdrawal period, animals in the 1000 mg potency/kg group showed again soft or mucous feces and a marked decrease in body weight. Of these animals, one male died and another male was sacrificed in a moribund state at about 2 weeks of the withdrawal period. Enterocolitis was observed in these cases. Almost all animals recovered within 3 weeks of withdrawal. A supplemental study of the 6-month toxicity study was conducted to examine the mechanisms of enterocolitis and the changes observable in the 100 or 300 mg potency/kg groups after drug withdrawal. As a reference, cefdinir (CFDN), an oral cephem antibiotic the same as S-1090, was added in the 1000 mg potency/kg group. No deaths occurred in any groups. Decreased intestinal flora were noted in all the groups treated with S-1090 or CFDN at the end of the dosing period. At 2 weeks of the withdrawal period, C. difficile and its D-1 toxin in the cecal contents were highly detected in the S-1090 300 and 1000 mg potency/kg groups and CFDN group. Inflammatory changes in the cecum and colon were observed in these groups. At 4 weeks of the withdrawal period, intestinal flora in the S-1090 groups almost returned to the condition before dosing, but those in the CFDN group were retained highly. Cecal D-1 toxin in the CFDN group was positive and higher than in the S-1090 groups. It was thus considered that the critical condition with enterocolitis resulted from C. difficile, which proliferated more rapidly than the other bacteria and D-1 toxin produced by this bacteria in the withdrawal period. Above changes were commonly observed in the CFDN group. The NOAEL of S-1090 was assessed to be 100 mg potency/kg/day which induced no enteritis.

Administration, Oral↗
PubMed2001

Effects on the optokinetic system of midline lesions in the pretectum of monkeys.

The nucleus of the optic tract (NOT), an important visuo-motor relay between the retina and preoculomotor structures, is responsible for mediating horizontal optokinetic nystagmus (OKN) in monkeys, cats, rabbits and rats. In addition to its projection to the vestibular nuclei, the NOT has a prominent projection to the contralateral NOT via the posterior commissure. In order to evaluate the role of the commissural fibers between the NOTs in OKN, we cut the posterior commissure in three Macaca fuscata. The animals viewed the OKN stripes under three conditions: right eye viewing, left eye viewing, and both eyes viewing. OKN was recorded in response to counter-clockwise and clockwise stimulation at stimulus velocities of 30 degrees/s, 60 degrees/s and 90 degrees/s. After control data were gathered, the posterior commissure was transected with an operating knife. Before the animal was sacrificed, biocytin, an anterograde tracer, was injected into the left NOT in order to confirm that all of the commissural fibers had been cut. Although the midline lesions decreased the initial rapid rise and steady state OKN slow-phase velocity in all three animals, there were no directional differences observed during monocular clockwise or counter-clockwise visual stimulation to either eye. In two of the three animals, there were no significant differences in the time-constants of optokinetic after nystagmus (OKAN) after the lesion. In the remaining animal, the time-constants decreased at stimulus velocities of 30 degrees/s and 60 degrees/s. In conclusion, gain reduction in the rapid rise and steady state slow-phase velocity of OKN can be explained by removal of an excitatory signal mediated by commissural fibers to inhibitory interneurons in the contralateral NOT. However, interrupting the commissural fibers had no effect on the velocity storage mechanism, because the time-constants of OKAN mostly remained largely unchanged by the lesion.

Animals↗
PubMed2000

Impact of Helicobacter pylori infection on gastric cancer incidence in a general Japanese population: the Hisayama study.

BACKGROUND: Several nested case-control studies have reported the potentially causal relationship between Helicobacter pylori infection and the development of gastric cancer. However, there has been no prospective study evaluating this issue. The purpose of this study is to examine the impact of H pylori infection on gastric cancer occurrence in a general Japanese population (Hisayama, Japan) stratified according to sex, using a prospective study design. METHODS: A total of 2602 subjects aged 40 years or older (1070 men; mean age, 57 years; 1532 women; mean age, 59 years) without a history of gastrectomy or gastric cancer were classified according to the status of the serum IgG antibodies to H pylori and observed prospectively for 9 years from 1988. RESULTS: Infection of H pylori was more common in men (71.5%) than in women (62.5%; P<.001). The age-adjusted incidence of gastric cancer for men (5.3 per 1000 person-years) was 4-fold higher than that for women (1.3; P<.001). In men, the age-adjusted incidence of gastric cancer was significantly higher in the subjects with H pylori infection than in those without it (6.2 vs 2.5; relative risk, 2.59 [95% confidence interval, 1.03-6.50]), whereas no significant difference was observed in women (1.2 vs 1.1; relative risk, 0.99 [95% confidence interval, 0.36-2.68]). These results were similar even after controlling for other risk factors in multivariate analysis. It was estimated that 40.1% of gastric cancers for men in this cohort were attributable to H pylori infection. CONCLUSION: A significant relationship exists between infection with H pylori and subsequent occurrence of gastric cancer for men but not for women in this Japanese population.

Adult↗
PubMed2000

Site-specific integration of a transgene mediated by a hybrid adenovirus/adeno-associated virus vector using the Cre/loxP-expression-switching system.

As vectors, adenoviruses (Ads) have many attractive advantages for in vivo gene therapy. However, Ads do not usually integrate into the host genome and gene expression is, thus, transient. Adeno-associated virus (AAV) integrates into a specific locus (AAVS1) on the human host's chromosome 19, while conventional recombinant AAV (rAAV) vectors do not possess this property because such vectors lack the rep gene. AAV vectors carrying the rep gene do not have enough space for insertion of a transgene. We have constructed a hybrid adenovirus/adeno-associated virus (Ad/AAV) vector which has the advantages of both Ads and AAVs. Given that the rep gene products inhibit propagation of Ads, we used the Cre/loxP-expression-switching system to regulate the expression of the rep gene. The Ad/AAV vector easily propagates, can efficiently infect a broad range of cell types, and can integrate into a specific locus on host chromosomes.

Adenoviridae↗
PubMed2000

Functional reconstitution of class II MHC-restricted T cell immunity mediated by retroviral transfer of the alpha beta TCR complex.

Transfer of the alphabeta TCR genes into T lymphocytes will provide a means to enhance Ag-specific immunity by increasing the frequency of tumor- or pathogen-specific T lymphocytes. We generated an efficient alphabeta TCR gene transfer system using two independent monocistronic retrovirus vectors harboring either of the class II MHC-restricted alpha or beta TCR genes specific for chicken OVA. The system enabled us to express the clonotypic TCR in 44% of the CD4+ T cells. The transduced cells showed a remarkable response to OVA323-339 peptide in the in vitro culture system, and the response to the Ag was comparable with those of the T lymphocytes derived from transgenic mice harboring OVA-specific TCR. Adoptive transfer of the TCR-transduced cells in mice induced the Ag-specific delayed-type hypersensitivity in response to OVA323-339 challenge. These results indicate that alphabeta TCR gene transfer into peripheral T lymphocytes can reconstitute Ag-specific immunity. We here propose that this method provides a basis for a new approach to manipulation of immune reactions and immunotherapy.

Adoptive Transfer↗
PubMed2000

Many multipotential gene-marked progenitor or stem cell clones contribute to hematopoiesis in nonhuman primates.

Retroviral insertion site analysis was used to track the contribution of retrovirally transduced primitive progenitors to hematopoiesis after autologous transplantation in the rhesus macaque model. CD34-enriched mobilized peripheral blood cells were transduced with retroviral marking vectors containing the neo gene and were reinfused after total body irradiation. High-level gene transfer efficiency allowed insertion site analysis of individual myeloid and erythroid colony-forming units (CFU) and of highly purified B- and T-lymphoid populations in 2 animals. At multiple time points up to 1 year after transplantation, retroviral insertion sites were identified by performing inverse polymerase chain reaction and sequencing vector-containing CFU or more than 99% pure T- and B-cell populations. Forty-eight unique insertion sequences were detected in the first animal and also in the second animal, and multiple clones contributed to hematopoiesis at 2 or more time points. Multipotential clones contributing to myeloid and lymphoid lineages were identified. These results support the concept that hematopoiesis in large animals is polyclonal and that individual multipotential stem or progenitor cells can contribute to hematopoiesis for prolonged periods. Gene transfer to long-lived, multipotent clones is shown and is encouraging for human gene therapy applications.

Animals↗
PubMed2000

Frequency of obstructive and mixed sleep apneas in 1,023 infants.

STUDY OBJECTIVES: To collect normative data on the frequency of obstructive and mixed sleep apneas in healthy infants. STUDY DESIGN: 1100 infants were recorded during one night in a sleep laboratory. SETTING: the recordings were performed in an infant sleep laboratory. PATIENTS: The recordings of 1023 infants were used for analysis, the data of 77 infants being excluded because of poor recording quality. The infants were born full-term, were healthy at the time of study, had no history of apnea and were aged between 2 and 28 weeks. The polysomnographic recordings were analyzed visually and were subdivided according to the age of the subjects into 2-7 weeks, 8-11 weeks, 12-15 weeks, 16-19 weeks and 20-27 weeks of life. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: At 2-7 weeks of life, obstructive apneas (p=.013) and mixed apneas (p=.004) were significantly more frequent than at any other age group. At 8 to 11 weeks of life, obstructive apneas were significantly more frequent in boys than girls (p=.016). CONCLUSIONS: The present findings add to our knowledge of infants' respiratory characteristics during sleep.

Female↗
PubMed2000

Assay of glycoamidases and endo-beta-N-acetylglucosaminidases by lectin capture and dissociation-enhanced lanthanide fluorescence immunoassay.

We have developed an assay system for endo-beta-N-acetylglucosaminidase and glycoamidase (PNGase), using Eu(3+)-labeled Man(9)GlcNAc(2) glycopeptides as substrates in combination with lectin capture. Two glycopeptides of different peptide lengths, derived from soybean agglutinin, were labeled with Eu(3+) via a diethylenetriaminepentaacetate (DTPA) chelating linker and served as substrates for two types of enzymes: one with (Man(9)GlcNAc(2))Asn for endo-beta-N-acetylglucosaminidase and the other with Ala-Ser-Phe-(Man(9)GlcNAc(2))Asn-Phe-Thr for glycoamidase activities. Following enzymatic hydrolysis, concanavalin A, immobilized or soluble, was added to the mixture to bind unreacted substrate and unlabeled hydrolysis product. The labeled peptide product could then be separated from the lectin-bound complexes by filtration for quantification by dissociation-enhanced lanthanide fluorescence immunoassay. Activities as low as 2 fmol min(-1) could be rapidly quantified for both types of enzymes, and enzymological parameters could be determined within minutes. Applicability of the assay was tested for identification of a glycoamidase activity peak in the fractionation of sweet almond emulsin, a classic example. This assay offers sensitivity, ease of use, and high throughput. In addition, it is versatile and should be applicable to other glycobiology enzyme systems.

Fluorescence↗
PubMed2000

Synthesis of neoglycoenzymes with homogeneous N-linked oligosaccharides using immobilized endo-beta-N-acetylglucosaminidase A.

A procedure for the enzymatic synthesis of neoglycoenzymes is described. The gene encoding endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) was overexpressed in Escherichia coli as a fusion protein linked to glutathione S-transferase (GST). GST-Endo-A fusion was extracted as a soluble protein. The fusion protein was purified to homogeneity with glutathione-Sepharose 4B and showed transglycosylation activity toward high-mannose-type glycopeptides without removing the GST moiety. The GST-Endo-A immobilized on glutathione-Sepharose 4B retained its transglycosylation activity. The immobilized enzyme could transfer (Man)(6)GlcNAc en bloc to partially deglycosylated ribonuclease B without damaging its enzyme activity. The immobilized GST-Endo-A should be very useful for synthesizing active neoglycoenzymes attached with homogeneous N-linked oligosaccharides.

Animals↗
PubMed2000

Prolonged high-level detection of retrovirally marked hematopoietic cells in nonhuman primates after transduction of CD34+ progenitors using clinically feasible methods.

Low-level retroviral transduction and engraftment of hematopoietic long-term repopulating cells in large animals and humans remain primary obstacles to the successful application of hematopoietic stem cell (HSC) gene transfer in humans. Recent studies have reported improved efficiency by including stromal cells (STR), or the fibronectin fragment CH-296 (FN), and various cytokines such as flt3 ligand (FLT) during ex vivo culture and transduction in nonhuman primates. In this work, we extend our studies using the rhesus competitive repopulation model to further explore optimal and clinically feasible peripheral blood (PB) progenitor cell transduction methods. First, we compared transduction in the presence of either preformed autologous STR or immobilized FN. Long-term clinically relevant gene marking levels in multiple hematopoietic lineages from both conditions were demonstrated in vivo by semiquantitative PCR, colony PCR, and genomic Southern blotting, suggesting that FN could replace STR in ex vivo transduction protocols. Second, we compared transduction on FN in the presence of IL-3, IL-6, stem cell factor (SCF), and FLT (our best cytokine combination in prior studies) with a combination of megakaryocyte growth and development factor (MGDF), SCF, and FLT. Gene marking levels were equivalent in these animals, with no significant effect on retroviral gene transfer efficiency assessed in vivo by the replacement of IL-3 and IL-6 with MGDF. Our results indicate that SCF/G-CSF-mobilized PB CD34+ cells are transduced with equivalent efficiency in the presence of either STR or FN, with stable long-term marking of multiple lineages at levels of 10-15% and transient marking as high as 54%. These results represent an advance in the field of HSC gene transfer using methods easily applied in the clinical setting.

Animals↗
PubMed2000

The healthy human infant tends to sleep in the prone rather than the supine position.

There are few reports about developmental behavior relating to roll over among healthy infants. We assessed the relationship between the placed position on sleeping and altered sleeping position the next morning by roll over among healthy infants. A health check-up clinic distributed a total of 1626 questionnaires to parents whose infant's ages are 1.5 years (or 18 months) old. The age at the first roll over and the change in sleeping position the next morning after they started to roll over, were investigated. The mean age of roll over from the supine to the prone among infants who were placed mainly in the prone sleeping position, at least in the first week of life, was 4.0 months (S.D., 1.1). The mean age of roll over from the supine to the prone among infants who were placed mainly in the supine sleeping position during early neonatal life and thereafter was 4.4 months (S.D., 1.2). The age of the first roll over from supine to prone was significantly younger in infants who were placed mainly in the prone sleeping position during early neonatal life. Among 651 infants who had been placed supine, 34.7% were found prone by roll over the next morning. Among 211 infants who had been placed prone, 14.2% were found supine by roll over the next morning. The number of infants who rolled over from supine to prone position was statistically greater than those from prone to supine. It is likely that the healthy human infant tends to sleep in the prone rather than the supine position. The finding is especially important for the correct assessment of the position in which SIDS cases were found dead.

Humans↗
PubMed2000

Aging effects upon smooth pursuit induced by step-ramp stimulation.

OBJECTIVE: in predictable target movements, pursuit gains are extremely close to 1.0. Under these conditions, aging effects upon pursuit have not been detected. Step-ramp stimuli produced by unpredictable combinations would be favorable procedures to assess the properties of smooth pursuit between young and aged people. METHODS: the target was a 0.5 degrees red laser spot. Eye movements of 49 normal subjects (26 younger subjects less than 49 years old and 23 older subjects more than 50 years old) were recorded with infrared reflection oculography and sampled at 250 Hz. Step direction and distance (2, 4, 6, 8 degrees) followed by 10 degrees /s ramp speed movement in the same (onward stimulus) or opposite to the direction (backward stimulus) were programmed in an unpredictable way before each set of ten tests. Both onward and backward stimulation were randomly given for each subject. RESULTS: in the onward study, there was a close correlation between retinal slip velocity (RSV) and eye acceleration (EA), which was expressed as a regression curve, being steeper in the younger group. This means that the younger subjects could produce faster velocity and greater acceleration than the aged group (P<0.05). CONCLUSION: subtle reduction in visual acuity, visual fields and contrast sensitivity will be one of possible causes, and the degradation of cortical areas crucial for visual processing might be one of possible causes of slowing of pursuit EA.

Acceleration↗
PubMed2000

Effect of adaptive plasticity of linear vestibulo-ocular reflex upon angular vestibulo-ocular reflex.

OBJECTIVE: The vestibulo-ocular reflex (VOR) produces compensatory eye movements during head movements. The VOR consists of the angular VOR and the linear VOR. The VOR is under adaptive control that corrects VOR performance when visual-vestibular mismatch arises during head movements. Most experiments concerning plasticity of the VOR have used the angular VOR. So far, there has been no investigation on the effect of adaptive plasticity of the linear VOR on the angular VOR. In this study, using a linear sled, we tested the hypothesis that the angular VOR is altered by changes in the linear VOR. METHODS: To modify the linear VOR, we used an adaptation paradigm. Eight subjects were translated sinusoidally at 0.125 Hz and 0.16 g peak acceleration along their inter-aural axis for 40 min, while viewing earth-fixed vertical stripes on the wall while wearing the binocular magnifying lenses. Six of the eight subjects showed an increase in linear VOR sensitivity after adaptation. Each of the six subjects who showed an increase in linear VOR sensitivity after adaptation also showed an increased angular VOR gain at 0.125 Hz. CONCLUSION: These results suggest that the linear VOR and the angular VOR share common neural pathways in such a way that a change in the synaptic efficacy of one pathway is accompanied by a commensurate change in the other.

Adaptation, Physiological↗
PubMed2000

Invertase production by Saccharomyces cerevisiae protoplasts immobilized in strontium alginate gel beads.

The invertase productivity of Saccharomyces cerevisiae IFO 0309 protoplasts in a static culture was 35 times (extracellular) and 9 times (extracellular + intracellular) higher than those of cells. When S. cerevisiae protoplasts were immobilized in 1.0% strontium alginate gel as an artificial cell wall, the protoplasts could be cultivated in a shake flask without disruption, and invertase was secreted into the broth. However, cell wall regeneration in the immobilized protoplasts was detected at about 24 h of cultivation. This implies that prevention of cell wall regeneration is a prerequisite for long term process with protoplasts. When 0.5 microg/ml aculeacin A (inhibitor of beta-1,3 glucan synthesis) was added to the broth, active protoplasts were maintained without cell wall regeneration for more than 24 h and invertase was produced extracellularly. Immobilized S. cerevisiae T7 protoplasts (this strain produces twice as much invertase as S. cerevisiae IFO 0309) were used for invertase production in a bubble column reactor, and a high and stable level of invertase (45 U/ml) was maintained for 72 h.

Journal Article↗
PubMed2000

The N-glycan acceptor specificity of a glucuronyltransferase, GlcAT-P, associated with biosynthesis of the HNK-1 epitope.

The acceptor specificity of a rat brain glucuronyltransferase, GlcAT-P, associated with biosynthesis of the HNK-1 epitope on glycoproteins, was investigated using asialoorosomucoid as a model acceptor substrate. Structural analysis of N-linked oligosaccharides, to which glucuronic acid was transferred by GlcAT-P, by means of two-dimensional mapping of pyridylamino-oligosaccharides and MS spectrometry, demonstrated that the enzyme transferred glucuronic acid to bi-, tri-, and tetra-antennary complex type sugar chains, with almost equal efficiency, indicating that the enzyme has no preference as to the number of acceptor sugar branches. Next, we studied the branch specificity of this enzyme by means of the selective branch scission method involving two step exoglycosidase digestion using authentic pyridylamino-oligosaccharides. The GlcAT-P is highly specific for the terminal N-acetyllactosamine structure and no glucuronic acid was incorporated into a Galbeta1-3GlcNAc moiety. The GlcAT-P transferred glucuronic acid to the galactose residues in the N-acetyllactosamine branches of bi-, tri-, and tetra-antennary oligosaccharide chains, with different efficiencies and most preferentially to those in the Galbeta1-4GlcNAcbeta1-4Manalpha1-3 branch.

Animals↗
PubMed2000

Risk of iron overload among middle-aged women.

Iron overload, expressed as increased body iron stores, has been recognized as a potential hazard because it promotes the generation of oxygen radicals. We analyzed factors associated with serum ferritin levels (an indicator of body iron stores) among middle-aged women with a high prevalence of nutrient supplement use. Serum ferritin concentrations were determined on automated immunoassay for 487 healthy women with the mean age of 57 years who participated in the New York University Women's Health Study. The mean serum ferritin concentration in postmenopausal women was more than twice that in premenopausal women. Serum ferritin concentrations progressively increased with advancing age, but adjustment for menopausal status considerably weakened this association. Among non-dietary factors, nonwhite ethnicity, obesity and cigarette smoking were positively associated with serum ferritin concentrations. After adjustment for these factors and for menopausal status, serum ferritin levels were positively associated with meat intake and multivitamin use and inversely associated with breakfast cereal consumption. However, none of these lifestyle factors positively associated with serum ferritin levels had a significant impact on serum ferritin levels above 100 ng/ml (approximately equal to median concentration). Our results suggest that iron overload seems unlikely among middle aged women through their diet and nutritional supplements.

Adult↗