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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 487 records · Page 27Linked to original sources

Down-regulation of S-adenosylhomocysteine hydrolase in the active methyl transfer system in the brain of genetically epileptic El mice.

To study the role of cerebral methylation in epileptogenesis, we investigated the active methyl transfer pathway in the brain of genetically epileptic El mice. We examined S-adenosylhomocysteine (AdoHcy) hydrolase activity (by high performance liquid chromatography), the corresponding mRNA levels (by competitive reverse transcription-polymerase chain reaction), as well as S-adenosylmethionine (AdoMet) and AdoHcy levels in epileptic El and non-epileptic control ddY mice. The level of AdoHcy, a potent feedback inhibitor in the methyl transfer system, was relatively high throughout growth, particularly in 15 week old El mice where it was increased approximately 20% compared to control ddY mice. AdoHcy hydrolase activity in the El mice brain did not increase during growth, which was confirmed by the finding that mRNA synthesis from the hydrolase gene behaved likewise. In contrast, ddY mice exhibited a gradual increase in the mRNA synthesis up to three fold and 20% increase in the enzyme activity at 15 weeks of age compared to those of El mice in which the seizure frequency was 100%. The levels of AdoMet, a versatile methyl donor, did not change throughout growth. We concluded that the down-regulation of AdoHcy hydrolase results in the accumulation of AdoHcy, possibly inducing an unstable state including seizures in the El mouse brain. El mice predisposed to epilepsy may be characterized by disordered feedback regulation of the AdoMet-dependent methyl transfer pathway.

Adenosylhomocysteinase↗

Purification and structural analysis of extracellular matrix of a skin tumor from a patient with juvenile hyaline fibromatosis.

Juvenile hyaline fibromatosis is a rare mesenchymal dysplasia that is inherited in an autosomal recessive fashion. The histological features of the tumor-like lesions are characterized by the deposition of amorphous hyaline material in the extracellular spaces of the dermis and soft tissues. We have analyzed the hyaline substance in a specimen of a skin tumor obtained from a 4-year-old Japanese girl with juvenile hyaline fibromatosis. It was found to consist mainly of type VI collagen; a small amount of type I collagen was also present. These components were separated by DEAE-cellulose ion-exchange chromatography under reducing conditions. The ratio of the dry weights of type I and type VI collagen was 1:4. Of the three chains of type VI collagen (alpha 1(VI), alpha 2(VI) and alpha 3(VI)), alpha 3(VI) was the most abundant. Glycosaminoglycans in the tumor tissue comprised dermatan sulfate, chondroitin sulfate and hyaluronan, with dermatan sulfate predominating. In contrast, hyaluronan is the most abundant in normal skin.

Amino Acid Sequence↗

Associations among upper airway structure, body position, and obesity in skeletal Class I male patients with obstructive sleep apnea.

Interactions between upper airway structure and posture in relation to obesity were studied in a sample of 61 adult Class I skeletal type male patients with obstructive sleep apnea (OSA) and 10 homologous control subjects. A pair of upright and supine lateral cephalometric films were taken for each subject. A Pearson correlation analysis identified significant r values for several demographic variables in patients with OSA such as apnea and hypopnea index, percentage of predicted neck circumference, minimum arterial oxygen saturation, and body mass index (BMI). The difference between cephalometric variables identified in upright and supine subjects was calculated. When patients with OSA changed their posture from upright to supine, significant correlations were observed between the cranial base to upper cervical column angle and the hypopharynx cross-sectional area and BMI. Moreover, the mandibular plane angle and the sella-nasion plane was significantly correlated with BMI. This occurred along with a significant positive correlation between the sella-nasion plane angle and BMI and a significant inverse correlation between the mandibular plane angle in reference to the absolute vertical and horizontal planes, with BMI after the positional change. Such correlations were not observed in control subjects. No correlations were observed between the variables related to the position of the hyoid bone with BMI in either patients with OSA or control subjects after the change in posture. On the basis of these findings, we propose that when patients with OSA change their body position from upright to supine (1) the patient's neck is more extended, and (2) the hyoid bone moves more anterosuperiorly in conjunction with an upward and forward rotation of the mandible. This change in craniofacial structure may be a compensatory geometrical change in the upper airway to secure its patency.

Adult↗

The effect of the tongue retaining device on awake genioglossus muscle activity in patients with obstructive sleep apnea.

Knowledge of how dental appliances alter upper airway muscle activity when they are used for the treatment of snoring and/or obstructive sleep apnea (OSA) is very limited. The purpose of this study was to define the effect of a tongue retaining device (TRD) on awake genioglossus (GG) muscle activity in 10 adult subjects with OSA and in 6 age and body mass index (BMI) matched symptom-free control subjects. The TRD is a custom-made appliance designed to allow the tongue to remain in a forward position between the anterior teeth by holding the tongue in an anterior bulb with negative pressure, during sleep. This pulls the tongue forward to enlarge the volume of the upper airway and to reduce upper airway resistance. In this study, two customized TRDs were used for each subject. The TRD-A did not have an anterior bulb but incorporated lingual surface electrodes to record the GG electromyographic (EMG) activity. The TRD-B contained an anterior bulb and two similar electrodes. The GG EMG activity was also recorded while patients used the TRD-B but were instructed to keep their tongue at rest outside the anterior bulb; this condition is hereafter referred to as TRD-X. The GG EMG activity and nasal airflow were simultaneously recorded while subjects used these customized TRDs during spontaneous awake breathing in both the upright and supine position. The following results were obtained and were consistent whether subjects were in the upright or the supine position. The GG EMG activity was greater with the TRD-B than with the TRD-A in control subjects (p < 0.05), whereas the GG EMG activity was less with the TRD-B than with the TRD-A in subjects with OSA (p < 0.01). Furthermore, there was no significant difference between the GG EMG activity of the TRD-A and the TRD-X in control subjects, whereas there was less activity with the TRD-X than with the TRD-A in subjects with OSA (p < 0.05). On the basis of these findings, it was concluded that the TRD has different effects on the awake GG muscle activity in control subjects and patients with OSA. The resultant change in the anatomic configuration of the upper airway caused by the TRD may be important in the treatment of OSA because such a change may alleviate the impaired upper airway function.

Adult↗

Cephalometric comparisons of craniofacial and upper airway structure by skeletal subtype and gender in patients with obstructive sleep apnea.

To investigate whether patients with obstructive sleep apnea (OSA) have abnormalities in their craniofacial and upper airway (UA) structures compared with normal subjects, cephalometric comparisons were systematically performed in both the upright and the supine positions in subjects with and without OSA, who were then grouped according to their craniofacial skeletal type and gender. A total of 347 patients with OSA and 101 control subjects were divided into male and female groups and then classified into Class I (CI), Class II, Division 1 (CII/1), Class II, Division 2 (CII/2), and Class III (CIII) skeletal subtypes. In the upright position, the most atypical craniofacial and UA structure was shown in male patients with CI OSA. In patients with OSA, the degree of UA abnormalities was less in the supine position regardless of skeletal subtype. In the supine position, the most atypical craniofacial and UA structure was also shown in male patients with CI OSA; there were no significant differences between male patients with CII/2 OSA and control subjects or between female patients with CI OSA and control subjects. With a change in body position from upright to supine, distinctive changes in the UA structure in both patients with OSA and control subjects occurred, according to skeletal subtype and gender. We conclude that there are a series of characteristics of craniofacial and UA structure that differ between patients with OSA and control subjects matched for skeletal subtype and gender. These differences may predispose to UA obstruction during sleep in patients with OSA.

Adult↗

Increased histidine preference during specific alteration of rhythm of environmental temperature stress in rats.

It has been reported that specific alteration of rhythm of environmental temperature (SART) stress induces various physiological changes. In this study, changes in taste preference during SART stress were investigated in rats. Rats were given free access to six amino acid solutions, saline, and water in a choice paradigm. During SART stress, daily food intake increased significantly by 50% whereas the rate of body weight gain decreased significantly to one third that observed during the prestress baseline period. In addition, consumption of histidine solution increased significantly, whereas intakes of water, monosodium glutamate, saline, glycine, arginine, lysine, and threonine were unaffected. Results suggest that a specific preference for histidine emerges during SART stress, which may be related to the stress-induced changes in the histamine turnover in the brain and peripheral tissues.

Acclimatization↗

A tongue retaining device and sleep-state genioglossus muscle activity in patients with obstructive sleep apnea.

To define the effect of a tongue retaining device (TRD) on genioglossus (GG) muscle activity in seven obstructive sleep apnea subjects, two overnight sleep studies were carried out with two TRDs. TRD-A had no anterior bulb and incorporated two electrodes to record GG electromyographic (EMG) activity. TRD-B had a bulb and it had electrodes similar to those in TRD-A. Episodes of apnea/hypopnea (AH) were analyzed during both rapid eye movement (REM) and non-REM (NREM) sleep. The peak GG muscle activity was measured for the breath immediately before the AH (pre-AH), for the first (first-E) and last (last-E) inspiratory efforts during the AH, and for the first breath after the AH (post-AH). The time lag between the peak GG EMG activity and the maximum inspiratory effort was calculated. The AH index decreased with both TRDs. The peak GG EMG activity preceded the maximum inspiratory effort throughout the periods, however the time lag changed considerably with TRD-A. The time lags with TRD-A and TRD-B differed significantly for the first-E and the last-E during NREM sleep and for the first-E during REM sleep. The TRD reduces AH severity, normalizes the time lag, and counteracts fluctuating GG EMG activity observed when no bulb is present.

Adult↗

Overexpression of Ca2+/calmodulin-dependent protein kinase II inhibits neurite outgrowth of PC12 cells.

To investigate the physiological role of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in neuronal differentiation, we transfected the cDNA of the alpha subunit of mouse CaM kinase II (CaM kinase II alpha) into PC12 cells and established clonal cell lines that constitutively express the transfected CaM kinase II alpha gene. The expression of CaM kinase II alpha was confirmed by northern blot and immunoblot analyses. Northern blot analysis showed that the gamma and delta subunits of CaM kinase II are mainly expressed in PC12 cells. Treatment of the cells with ionomycin activated CaM kinase II alpha through autophosphorylation and generation of the Ca2+/calmodulin-dependent form. It is interesting that the neurite outgrowth induced by dibutyryl cyclic AMP was inhibited in these cell lines in accordance with the activities of overexpressed CaM kinase II alpha. The activity of cyclic AMP-dependent protein kinase showed similar levels among these cell lines. These results suggest that CaM kinase II is involved in the modulation of the neurite outgrowth induced by activation of the cyclic AMP system.

Animals↗

Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans.

BACKGROUND & AIMS: Acute ischemic diseases of the small bowel are lethal emergencies with no reliable diagnostic biochemical tests available. Experimental studies have suggested rat intestinal fatty acid-binding protein (I-FABP) as a serum marker reflecting bowel ischemia; the present study evaluates the human homologue (human I-FABP) as a serum marker for the diagnosis of acute ischemic diseases of the bowel. METHODS: Enzyme immunoassay was applied to determine I-FABP levels in the sera of 96 subjects: 13 preoperative patients with ischemic bowel diseases (5 cases of mesenteric infarction and 8 cases of strangulated obstruction of the small bowel), 35 healthy subjects, and 48 hospitalized patients with acute abdominal pain. RESULTS: Serum I-FABP levels were < 65 ng/mL in healthy subjects. In patients with acute abdominal pain, levels ranged from < 20 to 87 ng/mL (mean, 27.4 ng/mL), not significantly different from findings in healthy subjects. However, patients with ischemic bowel disease showed significantly higher I-FABP levels, ranging from < 20 to 1496 ng/mL (mean, 265.8 ng/mL). All 5 patients with mesenteric infarction showed I-FABP levels of > 100 ng/mL. CONCLUSIONS: I-FABP is a useful biochemical marker for the accurate diagnosis of mesenteric infarction.

Adolescent↗

Analysis of micronucleus induction of pyrimethamine in in vitro CHL cells and in in vivo mouse bone marrow cells.

In vivo and in vitro mutagenicity of pyrimethamine were examined in the micronucleus test. Pyrimethamine strongly induced micronuclei in a dose-dependent manner in the in vitro micronucleus test using the Chinese hamster lung (CHL) cell line, when treated at 0.2-1.6 micrograms/ml for 48 h. The in vivo micronucleus test was carried out in mice after the first, second, third and fourth administration of doses up to 40 mg/kg p.o. The results showed no increased frequency of micronuclei after any treatment, though pyrimethamine was shown to persist at levels > 2 micrograms/ml in plasma after a single oral administration of 50 mg/kg.

Animals↗

HLA class I antigens in Japanese patients with melanoma.

In this study, we analyzed the frequencies of human leukocyte antigen (HLA) class I alleles in 110 Japanese patients with melanoma using serological methods, and compared such frequencies with clinical parameters. As expected, frequencies of HLA allele distribution in patients with melanoma reflected the frequencies observed in the normal Japanese population. Because these are different from populations belonging to other races (e.g., white), it followed that the HLA allele distribution in melanoma patients varies among different races. This differences may have significant implications for T-cell-mediated, HLA-restricted therapeutic modalities. No significant associations between HLA and clinical parameters were noted in this study. This report may help design future clinical trials involving therapeutic approaches based on HLA-restricted mechanisms.

Adult↗

Optimal pedaling rate estimated from neuromuscular fatigue for cyclists.

This study was designed to examine the optimal pedaling rate for pedaling exercise at a given work intensity for cyclists. Six college-aged cyclists each performed six sessions of heavy pedaling exercise at individually selected work rates based on their aerobic capacity. The optimal pedaling rate was evaluated on the basis of minimal neuromuscular fatigue as evidenced by the integrated electromyogram (iEMG) slope defined by the changes in iEMG as a function of time. The means of the iEMG slope demonstrated a quadratic curve versus pedaling rate. The mean values at 80 rpm (0.53 (SD 0.20) microV.min-1) and 90 rpm (0.67 (SD 0.23) microV.min-1) were significantly smaller than those values at any other pedaling rate. On the other hand, the mean value of oxygen uptake (VO2) expressed as a percent of the subject's maximal VO2 (% VO2max) at each pedaling rate also showed a quadratic curve with minimal values at about 60 or 70 rpm. VO2 at 70 rpm (84.0 (SD 5.0) % VO2max) was significantly smaller than those values at 80 rpm (86.3 (SD 3.5) % VO2max), 90 rpm (87.4 (SD 3.8) % VO2max), and 100 rpm (90.1 (SD 3.8) % VO2max). These data strongly suggest that the optimal pedaling rate estimated from neuromuscular fatigue in working muscles is not coincident with the pedaling rate at which the smallest VO2 was obtained, but with the preferred pedaling rate of the subjects. Our findings also suggest that the reason that cyclists prefer a higher pedaling rate is closely related to the development of neuromuscular fatigue in the working muscles.

Adult↗

A simple method for diagnosing xeroderma pigmentosum variant.

Patients with xeroderma pigmentosum variant have been diagnosed based on a post-replication repair assay using their cells together with their clinical manifestations. We present here an alternative simple method for the diagnosis of xeroderma pigmentosum variant that measures three cellular markers for DNA repair by autoradiography, unscheduled DNA synthesis, recovery of RNA synthesis, and recovery of replicative DNA synthesis after ultraviolet irradiation. Fibroblasts from a patient are plated on three coverslips parallel with normal cells (control). Unscheduled DNA synthesis, recovery of RNA synthesis, and recovery of replicative DNA synthesis after ultraviolet irradiation in the patient's cells are compared with those of adjacent normal cells by counting numbers of grains on nuclei for each coverslip. Of the hereditary photosensitive disorders including xeroderma pigmentosum, Cockayne syndrome, and newly established ultraviolet-sensitive syndrome, only xeroderma pigmentosum variant cells exhibit normal unscheduled DNA synthesis, normal recovery of RNA synthesis, but reduced recovery of replicative DNA synthesis (approximately 50% of that of control cells). This reduction of DNA synthesis is enhanced in the presence of caffeine. Because each disorder yields a different combination of these three markers, this method also provides a systematic basis for the diagnosis of these diseases.

Autoradiography↗

A case of lymphocutaneous nocardiosis with a review of lymphocutaneous nocardiosis reported in Japan.

An 82-year-old Japanese male developed nodules and ulcers along the lymphatics after a fall in the garden of his house resulting in injuries to the dorsum of his left hand which lasted for 3 months. Nocardia brasiliensis was isolated from a nodule, supporting a diagnosis of the lymphocutaneous type of nocardiosis. He had previously developed generalized bone metastasis from prostatic cancer, and his resulting depressed immunity might have played a part in the nocardiosis genesis. Sixteen cases of the lymphocutaneous type of nocardiosis reported in Japan were reviewed.

Abscess↗

Giant basal cell carcinoma associated with systemic amyloidosis.

A large basal cell carcinoma, 39 x 26 cm in size, is presented as second in size only to the largest basal cell carcinoma documented (40 x 30 cm), reported by Beck and co-workers (1). A 61-year-old Japanese male visited our clinic with a huge ulcerating tumor on the back. He had hidden the tumor for the previous 30 years. The tumor was histologically confirmed as basal cell carcinoma. The condition was associated with anemia, hypoproteinemia, and dyspnea, and with systemic amyloidosis in the skin, in the lymph nodes, and in the intestinal canal. On admission, the tumor had metastasized to the regional lymph nodes, and, about two years after the first operation, there were metastases to bone and lung, leading to death due to respiratory failure.

Amyloidosis↗

Production of murine leukemia RLmale1 rejection antigen peptide pRL1a by proteolysis of natural precursor pRL1b.

In this study, we demonstrated that NH2-terminal Ser and Ile residues of pRL1b (SI-pRL1a) (SIIPGLPLSL) are not involved in the recognition by RLmale 1-specific cytotoxic T lymphocyte. The sensitization activity observed with pRL1b (SI-pRL1a) was not greater than that of peptides substituted with irrelevant amino acids at these positions. In serum-free medium, pRLla retained sensitization activity, but pRL1b (SI-pRL1a) did not. Furthermore, addition of bestatin to serum-containing medium blocked sensitization by pRL1b (SI-pRL1a). On the other hand, the addition of captopril enhanced it, probably by inhibiting the degradation of pRL1a by ACE. pRL1a-D peptide with D-Ile in place of the L-Ile residue of pRL1a (IPGLPLSL) showed sensitization, but SI-pRLla-2,3D peptide, which has D-Iles in place of the L-Ile residues of pRLlb (SI-pRL1a), and which was not cleaved between the two D-Iles, did not. The findings suggest that pRL1a is the antigenic peptide bound to L(d) molecules and pRL1b (SI-pRL1a) peptide is its natural precursor, which generates pRL1a via proteolysis.

Animals↗

Soluble intercellular adhesion molecule-1 and soluble E-selectin levels in patients with atopic dermatitis.

The serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) were determined by double determinant immunoassay (DDIA), in 37 patients with atopic dermatitis (AD) and 31 age- and sex-matched healthy control subjects. Both sICAM-1 and sE-selectin levels were significantly higher in patients with AD than in healthy controls (P < 0.01), and were correlated with disease severity. A longitudinal study of patients with AD revealed that the levels of sICAM-1 decreased in those in whom symptoms improved. The sICAM-1 levels were significantly correlated with those of sE-selectin. Our studies suggest that such high levels of serum sICAM-1 and sE-selectin may affect the immune response in patients with AD. The levels of sICAM-1 and sE-selectin may be a useful immunological parameter for monitoring disease activity in AD.

Adolescent↗