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Biomedical subjects

T Yoda

Publications and source records attributed to T Yoda.

At least 37 records · Page 2Linked to original sources

Developmental changes in urinary elimination of theophylline and its metabolites in pediatric patients.

We investigated the developmental changes in the pattern of urinary metabolites of theophylline, a substrate for CYP1A2, to study when CYP1A2, which is absent in the perinatal period, fully develops during childhood. The urinary ratios of three metabolites (1-methyluric acid, 3-methylxanthine, and 1,3-dimethyluric acid) to theophylline in patients over 3 y of age show a much larger interindividual variation compared with those under 3 y of age, and the mean values of the ratios in patients over 3 y of age were greater than those in patients under 1 y of age. The urinary ratio of 1,3-dimethyluric acid (a metabolite generated by several cytochrome P450s) to 3-methylxanthine or 1-methyluric acid (metabolites generated by CYP1A2 exclusively) seemed to be relatively constant over 3 y of age; in patients under 3 y of age, these ratios were much higher than those in patients over 3 y of age. The urinary ratio of 1-methyluric acid to 3-methylxanthine or 3-methylxanthine to 1-methyluric acid seemed to be relatively invariable in all patients except those less than 1 y of age. These findings suggest that CYP1A2 activity may be programmed to mature by around 3 y of age and that CYP1A2 probably plays a major role in theophylline 8-hydroxylation at a therapeutic concentration after the full development of CYP1A2 activity.

Aging↗

Repeated acute hypoxia temporarily attenuates the ventilatory respiratory response to hypoxia in conscious newborn rats.

We asked whether repeated hypoxic exposures during the early neonatal periods could affect the ventilatory control, such as the lung volume-dependent ventilatory inhibition (HBR), pulmonary ventilation (VE), and CO2 production (VCO2). Within each litter of rats, one group of pups (experimental group H) was exposed to 6% O2 (30-min duration twice a day from postnatal d 1 to 4). The other group (control group C) was exposed to air. At 5 d after birth, the HBR was triggered by lung inflation via negative body surface pressure (10 cm H2O). Measurements of VE and VCO2 were done by plethysmography and the inflow-outflow CO2 difference, respectively. At 2 wk of age, VE and VCO2 measurements were repeated by the barometric technique and the inflow-outflow CO2 difference, respectively. Each conscious pup was breathing normoxia (21% O2) and then hypoxia (10% O2). Results were as follows: 1) during normoxia, HBR was stronger and both VE and VCO2 were higher in H pups than in C pups; 2) during hypoxia, the HBR of C was as in normoxia, whereas that of H was increased above the normoxic value; 3) during hypoxia, C maintained VE, whereas H decreased it; 4) in hypoxia, VCO2 was reduced significantly in both groups; 5) at 2 wk of age, VE and VCO2 did not differ between H and C during normoxia or in response to 10% hypoxia. We conclude that in rat pups, repeated hypoxic episodes can modify the HBR and, at least temporarily, reduce the VE response to hypoxia with a decrease in VCO2. The findings are in agreement with the view that repeated hypoxic exposures in the neonatal period could interfere with the development of respiratory control and could possibly be involved in the mechanisms of neonatal apnea or sudden infant death syndrome.

Animals↗

[Consent to enrollment in randomized clinical trials].

Multi-facility joint randomized clinical trials for cancer treatment are the most common method of current clinical study. However, the difference in the rate of participation in multi-facility randomized clinical trials may damage the resulting general validity. Therefore, we studied whether the rate of participation in randomized clinical trials is different between university hospitals and other general hospitals using a questionnaire (with anonymity preserved). There were 744 subjects from university hospitals and 339 from general hospitals participating in the study. The results showed that 10.9 percent of those from university hospitals were willing to participate, against 28.1 percent who were not. Of those from general hospitals (public hospitals in this study) 10.6 percent answered that they would participate and 27.4 percent that they would not. Little difference was found in the rate of participation in randomized clinical trials between university hospitals and other general hospitals. The focus is thus on doctors to solve the possible differences between the facilities in further multi-facility joint studies.

Adolescent↗

Efferent projection from the preoptic area for the control of non-shivering thermogenesis in rats.

1. To investigate the characteristics of efferent projections from the preoptic area for the control of non-shivering thermogenesis, we tested the effects of thermal or chemical stimulation, and transections of the preoptic area on the activity of interscapular brown adipose tissue in cold-acclimated and non-acclimated anaesthetized rats. 2. Electrical stimulation of the ventromedial hypothalamic nucleus (VMH) elicited non-shivering thermogenesis in the brown adipose tissue (BAT); warming the preoptic area to 41.5 C completely suppressed the thermogenic response. 3. Injections of d, l-homocysteic acid (DLH; 0.5 mM, 0.3 microliter) into the preoptic area also significantly attenuated BAT thermogenesis, whereas injections of control vehicle had no effect. 4. Transections of the whole hypothalamus in the coronal plane at the level of the paraventricular nucleus induced rapid and large rises in BAT and rectal temperatures. This response was not blocked by pretreatment with indomethacin. The high rectal and BAT temperatures were sustained more than 1 h, till the end of the experiment. Bilateral knife cuts that included the medial forebrain bundle but not the paraventricular nuclei elicited similar rises in BAT and rectal temperatures. Medial knife cuts had no effect. 5. These results suggest that warm-sensitive neurones in the preoptic area contribute a larger efferent signal for non-shivering thermogenesis than do cold-sensitive neurones, and that the preoptic area contributes a tonic inhibitory input to loci involved with non-shivering thermogenesis. This efferent inhibitory signal passes via lateral, but not medial, hypothalamic pathways.

Acclimatization↗

New apparatus for studying behavioral thermoregulation in rats.

The operant system described here contains a box that can be convectively heated or cooled. A rat moves freely in the box. Its location is monitored photoelectrically while its deep body temperature is monitored by a telemetry system. In heat-escape experiments, hot air (40 degrees C) flows through the box. When the rat enters a reward zone the air source is switched and cold air (0 degrees C) flows through the box for a given period (30 s). Conversely, in cold-escape experiments cold air flows through the box and when the rat enters the reward zone the air source is switched to a warm one. Experiments show that rats quickly learn to stay near the reward zone and move in and out of it periodically. This system is based on behavior more natural than the frequently used lever-pressing response, and has many advantages for use in studies involving behavioral thermoregulation.

Animals↗

[Relationship between aging and morphological bone changes of the condyle in temporomandibular disorders].

In order to clarify the clinical significance of morphological bone changes of the mandibular condyle in temporomandibular disorders, the relationship between radiographic bone changes and aging was clinically studied. The subjects of the study were 1,120 patients (812 females and 308 males). The average age was 33 years +/- 15 years (from 10 to 81 years of age). The 1,120 patients were divided into six age brackets (10 to 19 years, 20 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, 60 to 81 years). According to radiograms taken by lateral oblique transcranial projection, orbitcondyle projection and orthopantomography, the morphological bone changes were classified into seven groups, erosion, osteophyte, eburnation, flattening, deformity, concavity and sclerosis. The results were as follows: 1. The incidence of the patients with radiographic bone changes of the mandibular condyle increased with aging and showed significantly different age distribution from that without bone changes (Mann-Whitney U test: p < 0.01). 2. The incidence of erosion did not increase with aging and showed significantly different age distribution from osteophyte or eburnation (Mann-Whitney U test: p < 0.01, 0.05). The incidence of flattening also did not increase with aging and showed significantly different age distribution from osteophyte, eburnation or deformity (Mann-Whitney U test: p < 0.01, 0.05, 0.05).

Adolescent↗

Rapid and highly sensitive enzyme immunoassay for quantitative determination of tetrodotoxin.

A monoclonal antibody against tetrodotoxin (TTX) was obtained from Balb/c mice immunized with TTX-bovine serum albumin (BSA) conjugate. The monoclonal antibody was highly specific for TTX and had no cross-reaction to tetrodonic acid, which is a TTX derivative, or gonyautoxins, although a minor cross-reaction to anhydro-tetrodotoxin was observed. The monoclonal antibody neutralized the lethal activity of TTX. By using the monoclonal antibody, a rapid and highly sensitive competitive enzyme immunoassay (EIA) for quantitative analysis of TTX was developed. By the competitive EIA system, TTX can be determined quantitatively in about 30 min (90 min are required if the time for preparation of the solid-phase antigen was included), and the working range for quantitative analysis of TTX was 2-100 ng/ml. In recovery tests and examinations of TTX samples, results of the mouse bioassay and EIA analyses correlated well (r = 0.987). Moreover, it was demonstrated that low concentrations of TTX, which could not be detected by the mouse bioassay, could be determined quantitatively by the competitive EIA.

Animals↗

Cloning and sequencing of the chaperonin-encoding Cctd gene from Fugu rubripes rubripes.

CCT, a chaperonin containing t-complex polypeptide 1 (TCP-1), is a cytosolic molecular chaperone involved in the folding of proteins. We have isolated the Cctd gene from a Fugu rubripes rubripes (Frr) genomic library using a rat Ccta cDNA as a probe, and cloned its cDNA by reverse transcription-polymerase chain reaction (RT-PCR) using a pair of oligodeoxyribonucleotides corresponding to the 5' and 3' non-coding regions of Frr Cctd. Cctd spans a region of 4.7 kb and consists of at least 13 exons with small introns of about 144 bp on average. The Cctd cDNA sequence revealed a deduced polypeptide of 536 amino acids sharing a high degree of homology with that of the mouse Cctd cDNA (88%). Cctd is present as a single-copy gene, as shown by genomic Southern blot analysis, and can be used for evolutionary and classification analyses of Fugu species.

Amino Acid Sequence↗

[Systematic diagnosis and treatment method for temporomandibular disorders--new chart for primary diagnosis and treatment].

In this study, the classification of temporomandibular disorders of Japanese Society for Temporomandibular Joint was subdivided into ten types for the purpose of connecting directly with treatment, then a new chart for primary diagnosis and treatment were expressed. Ten types, i.e. type I (masticatory muscle disorders), type II (micro traumatic synovitis), type IIIc- (disk disorders except internal derangement; open lock, eminense click and crepitus), type IIIc+ (internal derangement; disc anterior displacement with reduction), type III L (internal derangement; disc anterior displacement without reduction, type IVo (osteoarthrosis with no TMJ symptoms), type IVp (osteoarthrosis with TMJ pain and no disc disorders), type IVc- (osteoarthrosis with crepitus, eminense click and open lock), type IVc+ (osteoarthrosis with internal derangement; disc anterior displacement with reduction), type IV L (osteoarthrosis with internal derangement; disc anterior displacement without reduction) 605 patients who visited our clinic from January 1994 to June 1994 were classified by the new chart for primary diagnosis; type I: 37 cases, type II: 142 cases, type IIIc-:56 cases, type III c+: 215 cases, type III L: 82 cases, type IVo: 8 cases, type IVp: 11 cases, type IVc-: 10 cases, type IV+: 19 cases, type IVL: 25 cases.

Clinical Protocols↗

Urinary glycylprolyl dipeptidyl aminopeptidase (GP-DAP) in insulin-dependent diabetic patients.

Urinary glycylprolyl dipeptidyl aminopeptidase (GP-DAP) concentrations were determined in 36 insulin-dependent diabetic children aged 4-18 years with a duration of diabetes ranging from 1 month to 14 years. Abnormal urinary GP-DAP concentrations were found in 19 of the 36 patients. Twelve of 27 patients without microalbuminuria also had increased urinary concentrations of GP-DAP. There was a significant correlation between urinary GP-DAP and plasma fructosamine (r = 0.52, p < 0.001). Our data suggest that urinary GP-DAP may be used as a marker for diabetic nephropathy. However, there is also a possibility that increased urinary GP-DAP concentrations are functionally related to poor metabolic control. Longitudinal studies are needed to establish the clinical usefulness of urinary GP-DAP.

Adolescent↗

A case of citrullinemia with abnormal messenger RNA for argininosuccinate synthetase.

A male neonate, thus far healthy and fed with breast milk, developed rapidly increasing apathy on the third day of life. Sucking became poor and hyperhidrosis was present. Hyperammonemia (3,305 micrograms/dl) was noted. He became comatose and died on the fourth day. There was a profound derangement of amino acid concentration in the body fluids, with highly elevated citrulline levels (4.70 mumols/ml in serum and 8.47 mumols/ml in urine). Autopsy showed diffuse pulmonary bleeding, as the only noteworthy pathological finding. The liver contained no detectable argininosuccinate synthetase (ASS) activity. The defect of ASS in the present case was not due to a reduced amount of ASSmRNA, but its structure was found to be abnormal; it was approximately 1.57 kb in length due to a defect of about 0.1 kb near the 3' end of the coding region.

Amino Acid Metabolism, Inborn Errors↗

[Autogenous dermal grafts for repair of temporomandibular joint disc perforations].

Perforations of the temporomandibular joints (TMJs) disc were made in the rabbits and repaired with autogenous dermal grafts. The healing process was investigated histologically. Twenty-one rabbits (forty-two TMJs) were divided into 3 experimental groups. Group 1. Six TMJs in which the superior aspects of the discs were exposed by the incision of the articular eminence. Group 2. Fifteen TMJs in which the discs were perforated. Group 3. Twenty-one TMJs in which the dermal grafts were sutured on the disc perforations. The results obtained were as follows: In group 2, all perforations were not repaired, except in one case. In group 3, 14/19 grafted disc perforations were repaired. One week after surgery, young, loose, collagenous tissue from the synovial membrane lined the margins of the perforations. Two weeks after surgery, vascularity from the synovial membrane and young collagen fibers were seen in the area of the repaired perforations. Four weeks after surgery, long and thick collagen fibers bridged the perforations.

Animals↗

Activation of idiotype-specific CD4+ T-cell line: cellular processing of exogenous self-immunoglobulin.

An idiotype (Id)-specific long-term cultured T-cell line has been generated from BALB/c mice immunized with M315 (alpha, lambda 2). The cell line comprises both CD3+ and CD4+ but CD8- cells. The T-cell line is stimulated in a class II major histocompatibility complex (MHC)-restricted manner, and is capable of producing interleukin-2 (IL-2) in response to the Id along with Iad-bearing antigen-presenting cells (APC). Fine Id specificity analysis has shown that changes in amino acid residues, Phe-94, Arg-95 and Asn-96, located on the VL-315, resulting from a somatic mutation mechanism of the mouse V lambda 2 gene, contribute to the T-cell activation. Pretreatment of APC with either glutaraldehyde or paraformaldehyde prevented both Fv-315 and VL-315 from triggering the T cells. This suggested that further processing of VL is required for T-cell activation. To clarify this point, we have generated a synthetic peptide, designated P18, which spans residues 91-108 of VL-315. In sharp contrast to VL, prefixed APC were capable of presenting P18 to stimulate the T-cell line to induce IL-2.

Animals↗

Structure of an abnormal messenger RNA for argininosuccinate synthetase in citrullinemia.

The structural abnormality of mRNA for argininosuccinate synthetase (ASS) and the structure of immune cross-reactive material for ASS (ASS-CRM) in the liver of a patient with type III citrullinemia were analyzed using dot and Northern blot hybridization, S1 nuclease analysis, and a sensitive enzyme-linked immunosorbent assay. The patient's liver contained no detectable ASS activity, the ASS-CRM content was about 0.5% of that in the control and the ASS mRNA content was almost normal. The ASS mRNA of the case was found to have an apparent structural abnormality; approximately 1.57 kb in length caused by a defect of about 0.1 kb near the 3' end of the coding region. Furthermore, gel filtration analysis revealed that the ASS-CRM had a molecular weight indistinguishable from the control ASS. These results indicate that the abnormal mRNA of the patient was translated in vivo to an immune-cross-reactive protein that was able to form a quaternary structure.

Amino Acid Metabolism, Inborn Errors↗