Biomedical subjects

S Shirakawa

Publications and source records attributed to S Shirakawa.

At least 55 records · Page 3Linked to original sources

PubMed1998

Changes in the structure of sleep spindles and delta waves on electroencephalography in patients with nocturnal enuresis.

OBJECTIVE: To evaluate the mechanism of the dysfunction of arousal in patients with Type I and Type IIa enuresis. PATIENTS AND METHODS: The numbers of sleep spindles and delta waves were analysed during electroencephalography in 19 patients with enuresis (17 male, two female, mean age 9.7 years, range 8-14). RESULTS: In four patients with Type I enuresis, who awoke spontaneously and remained dry as a result of urinary sensation, the numbers of sleep spindles and delta waves diminished gradually and finally disappeared just before the patients awoke completely. In the remaining nine patients with Type I enuresis, there was no decrease in the number of sleep spindles and delta waves, and enuresis occurred without the subjects awakening. In the six patients with Type IIa enuresis, there was no arousal reaction or generation of sleep spindles on urination while asleep. CONCLUSIONS: An immaturity in the function of the thalamus might be a cause of the arousal dysfunction in patients with Type I enuresis. In Type IIa enuresis, a possible abnormal or immature arousal mechanism in the pons or the lower tract may be responsible.

Adolescent↗

PubMed1998

Effects of the gradually increasing dawn light stimulation on sleep feeling.

Effects of a new lighting stimulation system upon subjective sleep and waking feeling were psychophysiologically examined in 24 healthy students in order to develop a way of obtaining comfortable awakening. The subjects underwent three different experimental conditions: the light stimulation condition, non-light stimulation condition and the control condition. The satisfaction of sleep was higher and day sleepiness lower in the light condition compared with the other two conditions. Subjective fatigue related to mental functions at waking was also smaller in the light condition compared with the other two conditions. These results suggest that the improvement of sleep feeling and waking seems to be achieved by gradual increased dawn light stimulation.

Adult↗

PubMed1998

Time course of saliva and serum melatonin levels after ingestion of melatonin.

Salival and serum melatonin levels after melatonin ingestion were measured by gas chromatography-mass spectrometry. Ingestion of 3 mg melatonin caused a marked increase in serum melatonin (3561+/-1201 pg/mL) within 20 min, followed by a gradual decrease, but the level still remained higher than the basal level at 240 min after the ingestion. The saliva melatonin 60 min after the ingestion showed the highest level (1177+/-403 pg/mL) which was one-third of the plasma level. The saliva melatonin level was highly correlated with the serum level throughout the experimental period (r=0.82, P=0.0001). These data indicate that the measurement of saliva melatonin level may be a suitable indicator for the melatonin secretion into general circulation.

Adult↗

PubMed1998

[Serum eosinophil cationic protein, urinary eosinophil protein X and urinary N-methylhistamine during acute asthma in children].

Serum eosinophil cationic protein (ECP), urinary eosinophil protein X (EPX) and urinary N-methylhistamine were investigated in 24 asthmatic children during acute asthma to determine the sequential variation in the parameters. Serum ECP levels and urinary EPX levels were high during acute asthma, and decreased gradually with improvement of acute asthma, however, these levels of eosinophil drived proteins were significantly higher than those in non-atopic children. There was no significant variation of urinary NMH levels. Significant inverse correlation was found between lung function and urinary EPX level. The present study suggests that serum ECP and urinary EPX may be useful for monitoring airway inflammation during acute asthma, and activation of eosinophils may persist after improvement of acute asthma.

Acute Disease↗

PubMed1998

[Epidemiology of sleep disorders].

The survey of insomnia, sleep breathing disorders and circadian rhythm sleep disorders in the world included Japan were reviewed in this article. We introduced the 1995 annual report of the national research project team supported by the grant of the Ministry of Health and Welfare that 18.7% of men and 20.3% of women in the outpatients of 11 general hospitals of Japan had severe sleep problems, and 11.7% of the patients had the persistent insomnia. Okada et al. estimated a prevalence of 3.28% of men for the obstructive sleep apnea syndrome in Japan. The survey by the telephone and self-reported questionnaire in the general population was reported that the prevalence of possible patients of circadian rhythm sleep disorders was estimated at 0.44% of Japanese.

Adult↗

PubMed1997

Physiological background of enuresis type I. A preliminary report.

The physiological background of enuresis Type I, which is due to a mild arousal dysfunction, has been investigated in two studies, one in rats and one in children with Type I enuresis. The results of these investigations suggest that in this type of enuresis, the fundamental arousal function following bladder distension, due to an arousal centre like the locus coeruleus and its network, is normal. In contrast, the process of multiplying the transient connection from light sleep to complete awakening, which probably relies upon functions of the thalamus and the further upper centrums, was thought to be abnormal.

Animals↗

PubMed1997

Clinical importance of interleukin-2 receptor alpha-chain expression in acute leukemia. The Japan Cooperative Group of Leukemia/Lymphoma.

To clarify the clinical importance of interleukin-2 (IL-2) receptor (IL-2R) expression in acute leukemia, we examined 517 adult patients with acute leukemia and CML blast crisis (CML-BC). IL-2R alpha was expressed in 42/311 AML, 5/11 acute unclassified leukemia, 24/116 pre-B ALL, 2/32 T-ALL, and 27/47 CML-BC, while IL-2R beta was expressed only in 2 T-ALL. Expression of IL-2R alpha was closely associated with that of different lineage markers, CD11b, CD34, and Ph1+ abnormality. IL-2R alpha(+) non-T leukemic cells did not respond to IL-2. Clinical outcome of IL-2R alpha (+) leukemia showed lower response to conventional chemotherapy and poorer prognosis than IL-2R alpha (-) cases. Serum IL-2R alpha level in IL-2R alpha (+) cases increased at the onset. Our findings indicate the diagnostic importance of IL-2R alpha expression in acute leukemia as a prognostic risk factor with a close relation to the particular cellular characteristics.

Acute Disease↗

PubMed1997

[Menogaril (TUT-7) late phase II study for malignant lymphoma, adult T-cell leukemia and lymphoma (ATLL)].

A late Phase II multicenter study with menogaril was conducted nationwide in patients with malignant lymphoma [non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD)], and ATLL, menogaril was orally administered at 100 mg daily after breakfast, for seven consecutive days with two- or three-week drug withdrawal, then menogaril administration was repeated. For malignant lymphoma, in 81 patients with NHL and 5 patients with HD registered, 70 and 5 patients were evaluable for efficacy, respectively. The efficacy rates were 32.9% (6 CRs + 17 PRs/70) for NHL and 20.0% (1 PR/5) for HD, respectively; that for the NHL patients with prior anthracycline antibiotic chemotherapy was 30.5% (5 CRs and 13 PRs/59). For ATLL, among the 16 patients registered, 15 were evaluable for efficacy, and the efficacy rate was 40.0% (2 CRs and 4 PRs/15). Adverse drug reactions frequently observed in the patients with malignant lymphoma and ATLL included bone-marrow suppression and gastrointestinal symptoms such as anorexia, and nausea/vomiting. With these results, menogaril was considered to be effective for the treatment of non-Hodgkin's lymphoma and ATLL.

Administration, Oral↗

PubMed1996

Immunohistochemical and immunoblotting identification of protein phosphatase 1 gamma 1 in rat salivary glands.

We have analyzed the distribution of the gamma 1 isotype of rat protein phosphatase type 1 catalytic subunit in rat salivary glands. Formaldehyde-fixed paraffin sections were reacted with the PP1 gamma 1 antibody using an immunohistochemical method. Positive staining occurred in striated ducts of parotid gland. However, the staining reaction was less intense in submandibular gland. Proteins were also prepared from rat salivary glands and subjected to SDS-PAGE, followed by Western blotting analysis with the PP1 gamma 1 antibody. The antibody interacted with protein corresponding to an estimated molecular mass of 36 kDa present in the parotid gland. The staining reaction was considerably weaker with the proteins from submandibular gland.

Animals↗

PubMed1996

Mosaic type of the nontoxic-nonhemaggulutinin component gene in Clostridium botulinum type A strain isolated from infant botulism in Japan.

The gene encoding the nontoxic-nonhemaggulutinin (NTNH) component was amplified by the PCR technique using two primer sets and the DNA template from Clostridium botulinum type A strain 7I03-H isolated from infant botulism in Japan. The nucleotide sequence revealed that the NTNH gene was composed of 1,193 amino acids with a molecular weight of 130868.08. Furthermore, the N-terminal half side and C-terminal half side of the NTNH component were similar to the NTNH component of type C and type A, respectively. These results indicate that the NTNH component gene codes the mosaic NTNH component composed of type A and type C. The hemaggulutinin gene, aha, and ORF-22 gene, orf-22a, were undetectable in the region upstream of the NTNH component gene, ant. Therefore, orf-22a is not thought to play a key role in the expression of botulinum type A progenitor toxin gene.

Amino Acid Sequence↗

PubMed1996

Characterization of component-I gene of botulinum C2 toxin and PCR detection of its gene in clostridial species.

Botulinum C2 toxin is composed of two nonlinked protein components, component-I (light chain) and component-II (heavy chain). It is produced by Clostridium botulinum types C and D, and is thought to play a lethal pathogenic role. These biological activities of C2 toxin may be due to the ADP-ribosylation of non-muscle actin by component-I of the toxin. We were able to isolate two overlapping gene fragments encoding component-I from the chromosomal DNA of Clostridium botulinum type C strain (C)-203U28, and determine the complete nucleotide sequence of component-I gene. The gene for component-I, bc21, consists of one open reading frame (ORF) encoding 431 amino acid residues (1293 nucleotides) without signaling peptide sequence. The molecular mass calculated from the deduced amino acid sequence was 49400.37 Da. Mono-ADP-ribosyltransferase activity was demonstrated in the lysate from E. coli transformed by the recombinant plasmid, pGEM-C2 encompassing whole component-I gene with its own promoter.

Amino Acid Sequence↗

PubMed1996

Accelerated cell-cycling of hematopoietic progenitors by the flt3 ligand that is modulated by transforming growth factor-beta.

Although hematopoietic growth factors have been extensively studied as to their roles in recruitment of hematopoietic progenitors from quiescence state to cell division state, little is known of their effects on cell-cycling of progenitors that have already transited from quiescence into active cell-cycling. We examined the effects of the flt3 ligand (FL) on cell-cycling of hematopoietic progenitors in serum-free culture. Results from our serial observations of colony formation and replating experiments suggest that FL enhances the rate of growth of interleukin-3 (IL-3)-dependent colonies by shortening the time for each progenitor in the colonies to divide. Cell-cycle analysis showed that shortening of cell-cycle time induced by FL is mainly because of alteration in the G1 phase that hematopoietic progenitors go through. We next investigated the role of transforming growth factor-beta (TGF-beta) in cell-cycling of progenitors, using TGF-beta protein and TGF-beta antisense oligonucleotides, because mRNA of TGF-beta was detected by reverse transcriptase polymerase reaction in blast cells that we used as a source of progenitors. TGF-beta lengthened the time required for IL-3-dependent progenitors to become two daughter cells, whereas the effects of TGF-beta antisense oligonucleotides were opposite to those of TGF-beta. The addition of TGF-beta neutralizing monoclonal antibodies to the cultures resulted in effects similar to those seen with TGF-beta antisense oligonucleotides. DNA studies indicated that both TBF-beta and TGF-beta antisense oligonucleotides change the length of G1 phase of the cell-cycle. TGF-beta abrogated the effects of FL on the growth rate of hematopoietic progenitors, whereas the combination of FL with TGF-beta antisense oligonucleotides exerted additive effects. These data show that FL has the potential to accelerate cell-cycling of hematopoietic progenitors, which is susceptible to the modulation by TGF-beta.

Animals↗

PubMed1996

Effects of a small dose of triazolam on P300 and resting EEG.

The aim of the present study was to clarify whether cognitive impairments caused by benzodiazepines (BDZs) are a consequence of their specific direct effects on cognitive function or whether they are explained as secondary effects of increased sleepiness. Ten healthy men (mean age, 33.9 years) participated in two experimental sessions in a randomized cross-over, double-blind study: in one session subjects were given a placebo and in the other they were given 0.125 mg triazolam (TRZ). Each experimental session was conducted on 1 day. After a pre-drug EEG recording and an event-related potential (ERP) recording, under an oddball paradigm, subjects took the TRZ or placebo orally at 1000 hours. Thereafter, EEG and ERP recording sessions, following the same procedure as the pre-drug sessions, were conducted at 1, 2, 4, 6 and 8 h after drug administration. The EEG and ERP recordings from Cz and Pz referred to the bilaterally linked ear electrodes were used. We found that P300 latency was significantly prolonged in TRZ condition at 2 h (Pz) and 4 h (Cz and Pz) after TRZ, and that the P300 amplitude was significantly reduced at 2 h (Cz and Pz) and 4 h (Pz) after TRZ, compared to the same times after placebo. The absolute power values for the theta (4-7 Hz), alpha 1 (8-9 Hz), and alpha 2 (10-12 Hz) bands did not differ at any measurement time between the treatments. Only the beta band (13-19 Hz) power value was significantly elevated after the TRZ administration (versus placebo). No significant sedative effects were detected in subjective measurements. These results indicate that a single oral dose of 0.125 mg TRZ caused cortical changes without distinct general sedation or subjective sleepiness.

Adult↗

PubMed1996

Anti-HIV-1 activity of thiadiazole derivatives: structure-activity relationship, reverse transcriptase inhibition, and lipophilicity.

The structure-activity relationship of the non-nucleoside HIV-1-specific reverse transcriptase (RT) inhibitors 4-phenyl-1,2,5-thiadiazol-3-yl N,N-dialkylcarbamate (TDA) derivatives was investigated with respect to their anti-HIV-1 activity, RT inhibition, and lipophilicity. 4-Phenyl-1,2,5-thiadiazol-3-yl N,N-dimethylcarbamate inhibited HIV-1-induced cytopathic effect (CPE) by 50% at a concentration of 28.8 microM in MT-4 cells. The activity increased more than 100-fold when the hydrogens at the 2-position and the 6-position in phenyl moiety were substituted by chlorines. However, the derivative with a chlorine at the 4-position of phenyl moiety did not show any inhibition of HIV-1 replication at its non-toxic concentrations. All of the 4-(2,6-dichlorophenyl)-1,2,5-thiadiazol-3-yl N-methyl-N-alkylcarbamates proved inhibitory to HIV-1 replication in the nanomolar concentration range. The TDA derivatives that showed anti-HIV-1 activity also inhibited RT activity in an enzymatic assay. However, the TDA derivatives did not show any specific inhibition of a non-nucleoside RT inhibitor (NNRTI)-resistant mutant and its RT activity. When the TDA derivatives were examined for their inhibitory effect on HIV-1 replication in the presence of 50% human serum, the activity significantly decreased depending on-their lipophilicity.

Anti-HIV Agents↗

PubMed1996

Feasibility of salvage chemotherapy for refractory or relapsed non-Hodgkin's lymphoma with two topoisomerase II inhibitors, MST-16 and VP-16. MST-16 Study Group.

A feasibility study was carried out on the treatment for refractory and relapsed non-Hodgkin's lymphomas with a combination of two oral topoisomerase II inhibitors, MST-16 and VP-16. On the basis of the synergistic activity in preclinical studies and the schedule dependency in these drugs, low-dose and long-term administration was planned. For the anticipated myelosuppression, two different regimens were designed as an open label trial in this study. In Regimen I, 400 mg of MST-16 combined with 25 mg of VP-16 was administered daily. With this regimen, the response rate (RR)/median time to tumor progression (TTP) in all evaluable patients was 50% (2/4)8.5 months in low grade (indolent) lymphoma and 60% (6/10)/5.2 months in intermediate/high grade (aggressive) lymphomas. In Regimen II, 400 mg of MST-16 combined with 25 mg of VP-16 was administered intermittently (3 days a week or every other day). With this regimen, there was an RR/median TTP of 60% (3/5)/7.0 months in indolent lymphoma and 33.3% (4/12)/1.1 months in aggressive lymphoma. A major side effect in both of these regimens was myelosuppression, with the incidence of grades 3 and 4 toxicity being higher in Regimen I than in Regimen II. The other side effects were uncommon and not severe. These findings indicated that two regimens were tolerated well and were promising for refractory and relapsed aggressive non-Hodgkin's lymphomas. To define the anti-tumor activity and safety of these regimens precisely, large-scale prospective randomized trials are necessary.

Adolescent↗

PubMed1996

Transblot identification of avidin-interacting proteins in rat salivary glands.

Blotting of rat parotid gland proteins separated by SDS-PAGE and transferred to Immobilon transfer membranes revealed that avidin-peroxidase conjugate interacted with bands having estimated molecular weights of 72, 74, and 120 kDa. Even at the lowest concentration of avidin-peroxidase used in the general ABC method (1:2000 dilution), three bands were clearly discernible. The staining reaction of parotid gland proteins was eliminated on preincubating the proteins with native avidin. The staining reaction was markedly reduced with the proteins obtained from submandibular/sublingual glands.

Animals↗

PubMed1996

Combination phase I/II study of irinotecan hydrochloride (CPT-11) and carboplatin in relapsed or refractory non-Hodgkin's lymphoma. CPT-11/Lymphoma Study Group.

Irinotecan hydrochloride (CPT-11) is a new derivative of camptothecin which inhibits topoisomerase I. Phase II studies have demonstrated that CPT-11 is active against a broad spectrum of neoplasms including intractable non-Hodgkin's lymphoma. An early phase II study in lymphoma suggested that a schedule of daily infusions of 40 mg/m2/day for three or five consecutive days is more effective than a single infusion of 200 mg/m2 every three to four weeks. Carboplatin is also an active agent against lymphoma, and preclinical studies have shown that CPT-11 and its active metabolite have a synergistic effect with platinum compounds. To evaluate the maximal tolerated dose (MTD) and the therapeutic efficacy of CPT-11 in combination with carboplatin in relapsed or refractory non-Hodgkin's lymphoma, we conducted a combination phase I/II study. The starting dose of CPT-11 was 20 mg/m2/day (days 1 through 3 and 8 through 10), and dose escalations of 5 mg/m2/day increments were planned, with a fixed dose of carboplatin (300 mg/m2, day 1). Six of the eight patients receiving both agents at the starting dose level developed critical toxicities such as grade 4 hematologic (neutropenia 6/8, thrombocytopenia 1/8) and grade 3 non-hematologic toxicities (diarrhea 2/8, transaminase elevation 1/8). Further dose escalation of CPT-11 was halted, and the starting doses were judged to be the MTDs. The response rate (25%, 2/8) to the combination of the MTDs was not superior to that of CPT-11 alone in a previous phase II study (38%, 26/69), and the MTD of CPT-11 in combination with carboplatin was less than half the single-agent dose. We conclude that carboplatin is not recommendable for combination with CPT-11 in lymphoma patients. Other suitable agents for such a combination should be sought.

Abdominal Pain↗

PubMed1996

Delayed phase jumps of sleep onset in a patient with non-24-hour sleep-wake syndrome.

We studied a 30-year-old man with non-24-hour sleep-wake syndrome. To investigate the relationship between environmental light-dark cycles and his sleep-wake rhythm, we documented his sleep log and rectal temperature data without any therapeutic interventions. We found that 1) the patient's sleep-wake pattern consisted of two different components, appearing alternatively, with a period of 27.2 days: regular free-run (R free-run), consisting of a daily 30- to 60-minute regular delay of sleep onset; and jumping free-run (J free-run), with clusters of delayed (> 4 hours) phase jumps in sleep onset (DP jump): 2) the frequency of sleep onset was higher during late evening hours to midnight hours than in the daytime; 3) DP jumps occurred exclusively when the prior sleep onset was delayed into the daytime; and 4) a cluster of DP jumps was likely to start when the patient's low temperature zone (a period in which rectal temperature was below average) at subjective night was illuminated by sunlight. These results suggest that DP jumps in the patient may occur due to illumination of the delay portion of the phase-response curve.

Adult↗