Biomedical subjects

T Kubota

Publications and source records attributed to T Kubota.

At least 109 records · Page 6Linked to original sources

PubMed2001

DNA replication-coupled inactivation of DnaA protein in vitro: a role for DnaA arginine-334 of the AAA+ Box VIII motif in ATP hydrolysis.

The DnaA protein, which initiates chromosomal replication in Escherichia coli, is negatively regulated by both the sliding clamp of DNA polymerase III holoenzyme and the IdaB protein. We have found that, when the amount of minichromosome is limited in an in vitro replication system, minichromosomal replication-stimulated hydrolysis of DnaA-bound ATP yields the ADP-bound inactive form. The number of sliding clamps formed during replication was at least five per minichromosome, which is 2.7-fold higher than the number formed during incubation without replication. These results support the notion that coupling of DnaA-ATP hydrolysis to DNA replication is the outcome of enhanced clamp formation. We have also found that the amino acid substitution R334H in DnaA severely inhibits the hydrolysis of bound ATP in vitro. Whereas ATP bound to wild-type DnaA is hydrolysed in a DNA-dependent intrinsic manner or in a sliding clamp-dependent manner, ATP bound to DnaA R334H protein was resistant to hydrolysis under the same conditions. This arginine residue may be located in the vicinity where ATP binds, and therefore may play an essential role in ATP hydrolysis. This residue is highly conserved among DnaA homologues and also in the Box VIII motif of the AAA+ protein family.

Adenosine Triphosphate↗

PubMed2001

Evidence for a single nucleotide polymorphism in the KCNQ1 potassium channel that underlies susceptibility to life-threatening arrhythmias.

INTRODUCTION: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. METHODS AND RESULTS: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in approximately 11% of the Japanese population. This 1727G>A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S-KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT-KCNQ1 and G643S-KCNQ1 with KCNE1 resulted in approximately 30% reduction in the slow delayed rectifier K+ current I(Ks) without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. CONCLUSION: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild I(Ks) dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population.

Adult↗

PubMed2001

Clinical and mutational characteristics of X-linked agammaglobulinemia and its carrier identified by flow cytometric assessment combined with genetic analysis.

BACKGROUND: X-linked agammaglobulinemia (XLA), caused by mutations in Bruton's tyrosine kinase (BTK ), is the most common form of inherited antibody deficiency. We previously reported that a flow cytometric evaluation of BTK expression in monocytes could easily detect XLA as well as its carrier. OBJECTIVE: Our purpose was to perform further flow cytometric analysis in additional XLA families in Japan. METHODS: In all, 106 hypogammaglobulinemic males (from 91 families) of various ages with a lack of mature B cells (<1%) were investigated. RESULTS: Flow cytometric assessment revealed the deficient BTK expression status in 78 families (93 patients), and mutations in BTK were identified in 76 of 78 families with presumed XLA. Of the patients with normal BTK expression, 2 showed missense mutations in which the normal amount of altered BTK transcript would cause the XLA phenotype. As many as 30% of these patients with XLA were clinically or genetically recognized beyond 5 years of age. Higher concentrations (>300 mg/dL) of serum IgG were evident in the cases diagnosed among adults, seemingly preventing severe infections. Fifty-seven of 70 mothers of patients with BTK deficiency were diagnosed as obligate carriers on the basis of a bimodal BTK expression pattern. Nine of the remaining 13 mothers showing nonmosaic BTK expression had no mutations in 2 alleles; surprisingly, the other 4 mothers had the mutated alleles. CONCLUSIONS: A diagnostic approach based on flow cytometric assessment for XLA should be initially considered in genetic investigation of antibody deficiencies, regardless of the patient's age.

Adolescent↗

PubMed2001

Medical and socioenvironmental predictors of hospital readmission in patients with congestive heart failure.

BACKGROUND: Patients with chronic congestive heart failure (CHF) require frequent rehospitalization because of the exacerbation of CHF. It is of clinical importance to determine predicting factors for readmission to reduce this likelihood. Previous studies have focused primarily on the demographic and medical characteristics in selected subsets of patients. Therefore, within a broad cohort of consecutively hospitalized patients, we sought to identify not only demographic and medical predictors but also socioenvironmental factors associated with readmission. METHODS: We assessed demographic (age, sex), medical (etiology of CHF, New York Heart Association functional class, left ventricular ejection fraction, previous admission for CHF, length of hospital stay, comorbidity, and medications), and socioenvironmental variables (occupation, financial resources, living alone, and follow-up visits) in 230 patients discharged with a diagnosis of CHF and recorded hospital readmission. RESULTS: Within 1 year after discharge, 81 patients (35%) were readmitted. Five variables, including poor follow-up visits (odds ratio [OR] 4.9, 95% CI 2.0-11.8), previous admission for CHF (OR 3.3, 95% CI 1.8-6.1), no occupation (OR 2.6, 95% CI 1.2-5.5), longer hospital stay (OR 3.2, 95% CI 1.2-8.5), and hypertension (OR 2.0, 95% CI 1.1-3.7), were identified as significant independent predictors for readmission by multivariate logistic regression analysis. CONCLUSIONS: Our independent predictors of readmission support the importance of medical and socioenvironmental factors in the deterioration of CHF. Therefore interventions to decrease readmission should also target social management in all hospitalized patients.

Acute Disease↗

PubMed2001

Localization and role of endothelin-1 and endothelin receptors in the human Fallopian tube.

The present experiments were designed to investigate the localization and role of endothelin-1 (ET-1) and endothelin receptors (ET(A) and ET(B)) in human Fallopian tubes obtained from patients in the follicular phase. Immunohistochemical studies revealed the predominant localization of ET-1 and of ET(B) receptors in the tubal epithelium and also within the muscle layer to a lesser degree. ET(A) receptors were dominant within the muscle layer. Scatchard plot analysis of the [(125)I]ET-1 binding also revealed the localization of ET(A) and ET(B) receptors on the Fallopian tubal membrane. A dissociation equilibrium constant of 34.6 +/- 3.3 pmol/l and a maximum binding site concentration of 1137.0 +/- 239.1 fmol/mg protein were obtained from the Scatchard plot analysis. Treatment of Fallopian tubal strips with ET-1 produced a tonic contraction which was inhibited by an ET(A) antagonist but not by an ET(B) antagonist. However, the increase in frequency and decrease in amplitude of rhythmic contractions caused by ET-1 were modulated by the ET(B) antagonist but remained unaffected by the ET(A) antagonist. These results suggest that ET-1 modulates the motility of the Fallopian tube through excitation of ET(A) and/or ET(B) receptors and possibly plays some role in oocyte capture.

Adult↗

PubMed2001

Effector mechanism and clinical response of BAK (BRM-activated killer) immuno-cell therapy for maintaining satisfactory QOL of advanced cancer patients utilizing CD56-positive NIE (neuro-immune-endocrine) cells.

A new type of immuno-cell therapy called BRM-activated killer (BAK) therapy using non-MHC-restricted lymphocytes, CD56-positive cells, was devised. Peripheral blood lymphocytes were selected by immobilization with anti-CD3 monoclonal antibody and cultured for 2 weeks in the presence of IL-2. Thereafter, they were reactivated by 1,000 U/ml of IFN-alpha for 15 min. Twenty-six outpatients with cancer whose performance status were over 80% on Karnofsky scale were selected for this study. About 6 x 10(9) BAK cells were returned by intravenous drip infusion, at one month intervals at an outpatient clinic to each of 20 advanced cancer patients in whom many metastatic lesions were found postoperatively, and to 6 patients with no postoperatively detectable metastases. The proportion of CD56-positive cells increased from 20% to 50% with culture. CD56-positive cells have strong cytotoxic activity and produced 20 ng/10(9) cells of beta-endorphin, an intracerebral hormone. During the course of BAK therapy, we adopted the Face scale as a QOL indicator. The QOL of all patients remained satisfactory or improved. Beta-endorphin is thought to make patients feel well and maintains good QOL because of its potent analgesic, sedative activity. From that facts that CD56 is a neural cell adhesion molecule and a member of the Ig superfamily, and that the CD56-positive cell produces beta-endorphin, we concluded that the CD56-positive cell is a multifunctional, integrated NIE (neuro-immune-endocrine) cell. Administration of BAK cells allowed all 20 advanced cancer patients with metastases to survive for over one year. All 6 patients receiving the same therapy for prevention of postoperative metastasis have been recurrence-free for one to five years.

Aged↗

PubMed2001

Cyclin D1 antisense oligonucleotide inhibits cell growth stimulated by epidermal growth factor and induces apoptosis of gastric cancer cells.

The cyclin D1 protein is one of the cell cycle regulators required for cell cycle progression through G1 phase to S phase. The cyclin D1-cyclin-dependent kinase (CDK) system is thought to control the cell cycle through mediating extracellular signals from mitogens, such as epidermal growth factor (EGF). In this study, we attempted to examine the therapeutic effect of cyclin D1 antisense oligonucleotides (AS/D1) on cell proliferation and apoptosis of the gastric cancer cell line MKN-74, in the presence and absence of EGF-stimulation. Evaluation of cell survival and DNA synthesis revealed that enhanced cell growth following EGF-stimulation was completely inhibited by a 24 h pre-incubation with 100 nM AD/D1. This inhibition was down to 19.3% compared with maximal DNA synthesis after stimulation with 3 nM EGF alone. Western blotting demonstrated that while EGF-stimulation led to cyclin D1 over-expression, AS/D1 inhibited cyclin D1 protein expression. We also demonstrated the induction of apoptosis in MKN-74 cells by AS/D1. In conclusion, EGF-stimulated MKN-74 cell proliferation was inhibited by AS/D1, which could overcome EGF-induced cyclin D1 over-expression. AS/D1 also affected cell survival by inducing apoptosis through cell cycle arrest following cyclin D1 depletion. Thus, AS/D1 may be a candidate for use as a novel cancer therapy specifically targeted against the over-expression of cyclin D1 enhanced by EGF in malignant cells.

Apoptosis↗

PubMed2001

UCN-01 (7-hydoxystaurosporine) inhibits in vivo growth of human cancer cells through selective perturbation of G1 phase checkpoint machinery.

Mechanisms underlying tumor sensitivity to the antitumor agent UCN-01 (7-hydroxystaurosporine) were examined in the nude mouse model using three human tumor xenografts, two pancreatic cancers (PAN-3-JCK and CRL 1420) and a breast cancer (MX-1). UCN-01 antitumor activity was evaluated in terms of relative tumor weights in treated and untreated mice bearing the tumor xenografts. The activity of cyclin-dependent kinase 2 (CDK2), levels of p21 and p27 proteins, pRb status and cell cycle were evaluated. Induction of p21 and apoptosis were also assessed immunohistochemically in CRL 1420. UCN-01 was administered intraperitoneally at a dose of either 5 or 10 mg / kg daily for 5 days followed by a further 5 injections after an interval of 2 days. UCN-01 significantly suppressed the growth of both pancreatic cancers, but was ineffective against MX-1. p21 protein expression was markedly induced in the UCN-01-sensitive pancreatic carcinoma xenografts at both doses, but p21 induction was only evident in the UCN-01-resistant MX-1 at 10 mg / kg. MX-1 exhibited CDK2 activity that was 6-fold higher than that of pancreatic cancer strains, which may explain the resistance of MX-1 to UCN-01 despite the induction of p21 at the dose of 10 mg / kg. The UCN-01-sensitive tumors exhibited G1 arrest and increased levels of apoptosis, changes not observed in resistant MX-1. In conclusion, it appears that a determining factor of in vivo UCN-01 sensitivity involves the balance of CDK2 kinase activity and p21 protein induction, resulting in augmented pRb phosphorylation, G1 cell cycle arrest and apoptosis.

Alkaloids↗

PubMed2001

Paclitaxel and SN-38 overcome cisplatin resistance of ovarian cancer cell lines by down-regulating the influx and efflux system of cisplatin.

Cisplatin (DDP) is one of the key drugs used to treat patients with ovarian cancer, although resistance to DDP can occur. Paclitaxel and SN-38 (an active metabolite of irinotecan (CPT-11)) are two drugs that are effective in patients with DDP-resistant ovarian cancer. To study how these drugs may overcome the intrinsic and / or acquired resistance of cancer cells to DDP, we investigated the effect of a combination of DDP with paclitaxel and a combination of DDP with SN-38 on three ovarian cancer cell lines, RTSG (intrinsically resistant cell line), KF (DDP-sensitive cell line), and KFra (acquired resistant cell line obtained from KF). We found that these combinations showed additive to synergistic antitumor activity. A time-dependent platinum (Pt) accumulation was observed in the DDP-sensitive KF cell line, while a decrease occurred in the KFra cell line. Little accumulation was observed in RTSG. Intracellular Pt accumulation was increased in all three cell lines by exposure to paclitaxel or SN-38. Ouabain, a Na(+),K(+)-ATPase inhibitor, decreased Pt accumulation in KF and KFra cell lines and inhibited the paclitaxel- and SN-38-induced increases in Pt accumulation in these cell lines. When we assessed the mRNA levels of the multidrug resistance-associated protein (MRP), which may be an efflux pump for DDP, the combination of paclitaxel or SN-38 with DDP down-regulated these levels, which are up-regulated by DDP alone. These results suggest that paclitaxel and SN-38 overcome DDP resistance of ovarian cell lines by controlling intracellular accumulation of DDP via both the influx and efflux systems.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice.

The flavonoid nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), found in Citrus depressa Rutaceae, a popular citrus fruit in Okinawa, Japan, reportedly inhibits the production of pro-matrix metalloproteinase (proMMP)-1, 3, and 9 in rabbit synovial fibroblasts in vitro. In the present study, we demonstrated the inhibitory effects of nobiletin on the proliferation of the cancer cell line, TMK- 1, and its production of MMPs. In the SCID mouse model, we found that nobiletin inhibited the formation of peritoneal dissemination nodules from TMK-1. The enzymatic activity of MMP-9 expressed in culture medium obtained from a co-culture of TMK-1 and mouse fibroblastic cells was inhibited by nobiletin in a concentration-dependent manner. In the SCID mouse model, total weight of dissemination nodules was significantly lower in the treated group compared with the vehicle control group (0.07 g vs. 0.78 g, P = 0.0059). The total number of dissemination nodules was also significantly lower than in the vehicle control group (7.5 vs. 69.3 / body, P = 0.0001). These results suggest that nobiletin may be a candidate anti-metastatic drug for prevention of peritoneal dissemination of gastric cancer.

Animals↗

PubMed2001

The role of cytokines in physiological sleep regulation.

Several growth factors (GFs) are implicated in sleep regulation. It is posited that these GFs are produced in response to neural activity and affect input-output relationships within the neural circuits where they are produced, thereby inducing a local state shift. These GFs also influence synaptic efficacy. All the GFs currently identified as sleep regulatory substances are also implicated in synaptic plasticity. Among these substances, the most extensively studied for their role in sleep regulation are interleukin-1beta (IL-1) and tumor necrosis factor alpha (TNF). Injection of IL-1 or TNF enhances non-rapid eye movement sleep (NREMS). Inhibition of either IL-1 or TNF inhibits spontaneous sleep and the sleep rebound that occurs after sleep deprivation. Stimulation of the endogenous production of IL-1 and TNF enhances NREMS. Brain levels of IL-1 and TNF correlate with sleep propensity; for example, after sleep deprivation, their levels increase. IL-1 and TNF are part of a complex biochemical cascade regulating sleep. Downstream events include nitric oxide, growth hormone releasing hormone, nerve growth factor, nuclear factor kappa B, and possibly adenosine and prostaglandins. Endogenous substances moderating the effects of IL-1 and TNF include anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. Clinical conditions altering IL-1 or TNF activity are associated with changes in sleep, for example, infectious disease and sleep apnea. As our knowledge of the biochemical regulation of sleep progresses, our understanding of sleep function and of many clinical conditions will improve.

Adenosine↗

PubMed2001

Prevalence of age related maculopathy in a representative Japanese population: the Hisayama study.

AIM: To determine the prevalence of age related maculopathy (ARM) in a representative older Japanese population. METHODS: 1486 residents of Hisayama town, Fukuoka, Japan, aged 50 years or older were examined and the presence of ARM was determined by grading from fundus examination by indirect ophthalmoscope, slit lamp, and colour fundus photographs. RESULTS: The prevalence rate of drusen, which occurred with comparable frequency in men and women, was 9.6%. The frequency of drusen increased with age (p <0.01). Hyperpigmentation and/or hypopigmentation of the retina was present in 3.2%, geographic atrophy in 0.2%, and neovascular age related macular degeneration in 0.67%. The frequency of neovascular age related macular degeneration was significantly higher in the men (1.2% v. 0.34%, p <0.01). CONCLUSIONS: Early and late stage ARM is less common among Japanese people than among white people in Western countries, while late stage ARM is more common among Japanese than among black people.

Age Factors↗

PubMed2001

Effects of soluble TNF receptor treatment on lipopolysaccharide-induced myocardial cytokine expression.

Tumor necrosis factor (TNF)-alpha plays a key role in the pathogenesis of septic shock syndrome, and myocardial TNF-alpha expression may contribute to this pathophysiology. We examined the myocardial expression of TNF-alpha-related cytokines and chemokines in mice exposed to lipopolysaccharide (LPS) and tested the effects of anti-TNF therapy on myocardial cytokine expression. Cytokine mRNA levels were measured by RNase protection assay, and protein levels in the plasma and myocardium were assessed by enzyme-linked immunosorbent assays. LPS (4 microg/g body wt ip) induced marked cytokine expression, including TNF-alpha, interleukin (IL)-1beta, IL-6, and monocyte chemotactic protein (MCP)-1, in both the plasma and myocardium. Pretreatment with adenovirus-mediated TNF receptor fusion protein (AdTNFR1; 10(9) plaque-forming units iv) decreased plasma cytokine levels. In contrast, whereas myocardial IL-1beta expression was also suppressed, expression of IL-6 and MCP-1 was not inhibited by AdTNFR1. In summary, anti-TNF treatment differentially altered the cytokine expression in the plasma and myocardium during endotoxemia. Inability to block myocardial expression of IL-6 and MCP-1 suggests a possible mechanism for the failure of anti-TNF therapies in the treatment of endotoxin shock.

Adenoviridae↗

PubMed2001

Glial cell line-derived neurotrophic factor promotes sleep in rats and rabbits.

Various growth factors (e.g., growth hormone-releasing hormone, acidic fibroblast growth factor, nerve growth factor, brain-derived neurotrophic factor, and interleukin-1) are implicated in sleep regulation. It is hypothesized that neuronal activity enhances the production of such growth factors, and they in turn form part of the sleep regulatory mechanism. Glial cell line-derived neurotrophic factor (GDNF) promotes development, differentiation, maintenance, and regeneration of neurons, and its production is induced by well-characterized sleep regulatory substances such as interleukin-1 and tumor necrosis factor. Therefore, we investigated whether GDNF would promote sleep. Twenty-six male Sprague-Dawley rats and 30 male New Zealand White rabbits were surgically implanted with electroencephalogram (EEG) and electromyogram (EMG; rats only) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and on a separate day with one of the following doses of GDNF: 5, 50, and 500 ng in rabbits and 50 and 500 ng in rats. The EEG, brain temperature, EMG (in rats), and motor activity (in rabbits) were recorded for 23 h after the intracerebroventricular injection. GDNF (500-ng dose) increased the time spent in nonrapid eye movement sleep in both rats and rabbits. Rapid eye movement sleep was not affected by the lower doses of GDNF but was inhibited in rabbits after the high dose. EEG slow-wave activity was not affected by GDNF. The current results provide further evidence that various growth factors are involved in sleep regulation.

Animals↗

PubMed2001

Vagotomy attenuates tumor necrosis factor-alpha-induced sleep and EEG delta-activity in rats.

Much evidence suggests that tumor necrosis factor-alpha (TNF-alpha) is involved in the regulation of physiological sleep. However, it remains unclear whether peripheral administration of TNF-alpha induces sleep in rats. Furthermore, the role of the vagus nerve in the somnogenic actions of TNF-alpha had not heretofore been studied. Four doses of TNF-alpha were administered intraperitoneally just before the onset of the dark period. The three higher doses of TNF-alpha (50, 100, and 200 microg/kg) dose dependently increased nonrapid eye movement sleep (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave activity. TNF-alpha increased EEG delta-power and decreased EEG alpha- and beta-power during the initial 3 h after injection. In vagotomized rats, the NREMS responses to 50 or 100 microg/kg of TNF-alpha were attenuated, while significant TNF-alpha-induced increases in NREMS were observed in a sham-operated group. Moreover, the vagotomized rats failed to exhibit the increase in EEG delta-power induced by TNF-alpha intraperitoneally. These results suggest that peripheral TNF-alpha can induce NREMS and vagal afferents play an important role in the effects of peripheral TNF-alpha and EEG synchronization on sleep. Intraperitoneal TNF-alpha failed to affect brain temperature at the doses tested, thereby demonstrating that TNF-alpha-induced sleep effects are, in part, independent from its effects on brain temperature. Results are consistent with the hypothesis that a cytokine network is involved in sleep regulation.

Animals↗

PubMed2001

Interleukin-15 and interleukin-2 enhance non-REM sleep in rabbits.

Interleukin (IL)-15 and -2 share receptor- and signal-transduction pathway (Jak-STAT pathway) components. IL-2 is somnogenic in rats but has not been tested in other species. Furthermore, the effects of IL-15 on sleep have not heretofore been described. We investigated the somnogenic actions of IL-15 in rabbits and compared them with those of IL-2. Three doses of IL-15 or -2 (10, 100, and 500 ng) were injected intracerebroventriculary at the onset of the dark period. In addition, 500 ng of IL-15 and -2 were injected 3 h after the beginning of the light period. IL-15 dose dependently increased non-rapid eye movement sleep (NREMS) and induced fever. IL-15 inhibited rapid eye movement sleep (REMS) after its administration during the light period; however, all doses of IL-15 failed to affect REMS if given at dark onset. IL-2 also dose dependently increased NREMS and fever. IL-2 inhibited REMS, and this effect was observed only in the light period. IL-15 and -2 enhanced electroencephalographic (EEG) slow waves during the initial 9-h postinjection period, then, during hours 10-23 postinjection, reduced EEG slow-wave activity. Current data support the notion that the brain cytokine network is involved in the regulation of sleep.

Animals↗

PubMed2001

Interleukin-18 promotes sleep in rabbits and rats.

Interleukin (IL)-1beta is involved in physiological sleep regulation. IL-18 is a member of the IL-1 family, and its signal-transduction mechanism is similar to that of IL-1. Therefore, we hypothesized that IL-18 might also be involved in sleep regulation. Three doses of IL-18 (10, 100, and 500 ng) were injected intracerebroventricularly (icv) into rabbits at the onset of the dark period. The two higher doses of IL-18 markedly increased non-rapid eye movement sleep (NREMS), accompanied by increases in brain temperature (Tbr). These effects were lost after the heat inactivation of IL-18. The 500 ng of IL-18 injection during the light period also increased NREMS and Tbr. Similar results were obtained after icv injection of 100 ng of IL-18 into rats. Furthermore, intraperitoneal injection of 30 microg/kg of IL-18 slightly, but significantly, increased NREMS, whereas it significantly decreased electroencephalogram slow-wave activity in rats. Intraperitoneal IL-18 failed to induce fever. An anti-human IL-18 antibody had little effect on spontaneous sleep in rabbits, although the anti-IL-18 antibody significantly attenuated muramyl dipeptide-induced sleep. These data suggest that IL-18 is involved in mechanisms of sleep responses to infection.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2001

Prevalence of human immunodeficiency virus, hepatitis B and hepatitis C virus antibodies and hepatitis B antigen among commercial sex workers in Japan.

OBJECTIVE: To investigate the prevalence of antibodies to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and of hepatitis B surface (HBs) antigen in commercial sex workers (CSW) who attended a sexually transmitted disease (STD) clinic in Tokyo. METHODS: Surveys were conducted on 308 CSW and 384 control subjects for HIV antibody or 241 control subjects for HBs antibody and antigen and HCV antibody. RESULTS: HIV antibody was not detected in either CSW or control subjects. The positive rates for HBs antigen and antibody were 0.6 and 23.4%, respectively, in the CSW group, and 0.4 and 71.8% in the control group. The HCV antibody positive rate was 3.2% in the CSW group and 0.4% in the control group. CONCLUSION: A statistically significant difference between the two groups was observed only in HCV antibody positive rate. STD checkup for CSW alone is inadequate--STD health education and screening for the general public are also required.

Adult↗