HslO ameliorates arrested ΔrecA polA cell growth and reduces DNA damage and oxidative stress responses.

Chromosome damage combined with defective recombinase activity has been widely considered to render cells inviable, owing to deficient double-strand break repair. However, temperature-sensitive recAts polA cells grow well upon induction of DNA damage and supplementation with catalase at restrictive temperatures. These treatments reduce intracellular reactive oxygen species (ROS) levels, which suggests that recAts polA cells are susceptible to ROS, but not chronic chromosome damage. Therefore, we investigated whether polA cells can tolerate a complete lack of recombinase function. We introduced a ΔrecA allele in polA cells in the presence or absence of the hslO-encoding redox molecular chaperon Hsp33 expression plasmid. Induction of the hslO gene with IPTG resulted in increased cell viability in ΔrecA polA cells with the hslO expression plasmid. ΔrecA polA cells in the absence of the hslO expression plasmid showed rich medium sensitivity with increasing ROS levels. Adding catalase to the culture medium considerably rescued growth arrest and decreased ROS. These results suggest that hslO expression manages oxidative stress to an acceptable level in cells with oxidative damage and rescues cell growth. Overall, ROS may regulate several processes, from damage response to cell division, via ROS-sensitive cell metabolism.

Eugenol and Its Role in Chronic Diseases.

The active components in cloves are eugenol and isoeugenol. Eugenol has recently become a focus of interest because of its potential role in alleviating and preventing chronic diseases such as cancer, inflammatory reactions, and other conditions. The radical-scavenging and anti-inflammatory activities of eugenol have been shown to modulate chronic diseases in vitro and in vivo, but in humans, the therapeutic use of eugenol still remains to be explored. Based on a review of the recent literature, the antioxidant, anti-proliferative, and anti-inflammatory activities of eugenol and its related compounds are discussed in relation to experimentally determined antioxidant activity (stoichiometric factor n and inhibition rate constant) and theoretical parameters [phenolic O-H bond dissociation enthalpy (BDE), ionization potential (IP according to Koopman's theorem), and electrophilicity (ω)], calculated using a density functional theory method. Dimers of eugenol and its related compounds showed large antioxidant activities and high ω values and also exerted efficient anti-inflammatory activities. Eugenol appears to possess multiple antioxidant activities (dimerization, recycling, and chelating effect) in one molecule, thus having the potential to alleviate and prevent chronic diseases.

Cedar and cypress pollen counts are associated with the prevalence of allergic diseases in Japanese schoolchildren.

BACKGROUND: Patients allergic to pollen have been known to become more symptomatic during pollen season compared with the nonpollen season. However, there are few studies regarding whether higher exposure to pollen might increase the prevalence of allergic diseases. METHODS: An ecological analysis was conducted to evaluate whether pollen exposure is associated with the prevalence of allergic diseases in schoolchildren. Pollen count data of Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa), which are the major pollen allergens in Japan, were obtained from each prefecture. The prevalence of allergic diseases in schoolchildren in each prefecture was based on a nationwide cross-sectional survey using the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: After omitting three prefectures where pollen data were not available, data of 44 prefectures were analysed. The prevalence of allergic rhinoconjunctivitis in children aged 6-7 years was positively associated with both cedar and cypress pollen counts (P = 0.01, both), whereas the prevalence of allergic rhinoconjunctivitis in children aged 13-14 years was positively associated with only cypress pollen counts (P = 0.003). Furthermore, the prevalence of asthma was positively associated with cedar pollen counts in 6- to 7-year-old children (P = 0.003) but not cypress pollen counts in either age group. CONCLUSIONS: There are ecological associations between pollen counts and the prevalence of allergic diseases in Japanese schoolchildren. Further studies are needed to determine whether the difference between the effects of cedar and cypress pollens is attributable to pollen counts or allergenicity.

Evaluation of the basic properties of the BANGkit gel dosimeter.

We evaluated the basic properties of a commercially available BANGkit gel dosimeter, which is a normoxic type of BANG gel. This gel-kit has the same composition as the BANG 3 gel, but is fully oxygenated. To exclude oxygen, oxygen scavenging ascorbic acid and copper sulfate as a catalyst are used. The properties that we examined are the effects of the concentrations of copper sulfate and ascorbic acid on the response, the reproducibility, the long-term stability, the temperature effect at irradiation and the dose-rate effect. In our results, the excellent linear fit of the R2-dose response in a dose range for clinical use and its reproducibility were observed. The precision of a linear fit was preserved for about 3 weeks. The temperature at irradiation showed a significant effect on the dose response. Although the dose-rate dependence in the high-dose range was observed, it was negligible for the clinical dose range up to 270 cGy. In conclusion, this gel dosimeter is thought to be utilizable in clinical practice, while we have to pay attention to the temperature during the entire measurement processes, and additionally there is room for improvement in the linearity and the dose-rate dependence in the high-dose range.

Preoperative portal vein embolization with a mixture of gelatin sponge and iodized oil: efficacy and safety.

PURPOSE: To evaluate whether portal vein embolization (PVE) using a mixture of gelatin sponge (GS) pieces and iodized oil is safe and effective in inducing hypertrophy of the future liver remnants (FLR). MATERIAL AND METHODS: PVE was performed in 14 patients (eight male and six female, mean age 65 years, range 35-81 years) diagnosed with malignant liver tumor before surgery, whose FLR volumes were judged too small to allow for safe resection. Liver volume change, biochemical data change, complications related to PVE, and postoperative complications were retrospectively evaluated. RESULTS: PVE was successful in all patients, and there were no procedural complications. Absolute FLR volume and FLR/total liver volume (TLV) ratio increased by 102 cm3 and 8% (mean values), respectively. Planned hepatectomies were cancelled in three patients due to extrahepatic metastasis or bile duct infection. Five of the 11 patients (45%) who underwent hepatectomies had major postoperative complications. However, complications due to hepatic failure were not seen. In 10 patients, except one whose outcome was fatal outcome, the mean hospitalization days with and without major complications were 73 and 33 days, respectively. CONCLUSION: PVE using a mixture of GS and iodized oil seems to be effective and safe in inducing hypertrophy of the FLR.

Diffuse cerebral white matter T2-weighted hyperintensity: a new finding of general paresis.

General paresis (parenchymatous neurosyphilis) is a rare disease, and in recent years the number of papers published on the magnetic resonance imaging findings has been limited. The findings are as follows: cerebral atrophy; mesiotemporal T2 hyperintensity; ventriculomegaly; pathological T2 hypointensity of the globus pallidus, putamen, the head of the caudate nucleus and thalamus. We present a new finding, diffuse cerebral white matter T2 hyperintensity, observed in a patient with general paresis with a 5-year history of progressive dementia.

Clinical features and therapeutic outcomes of 65 patients with acromegaly at Tokyo Women's Medical University.

OBJECTIVE: The purpose of this study was to survey the clinical characteristics, complications, and therapeutic outcome in patients with acromegaly. PATIENTS AND METHODS: The clinical features of 65 patients with acromegaly (31 males, 34 females; mean age: 50+/-2 yr.) who were admitted to Tokyo Women's Medical University between 1990 and 1999 were analyzed retrospectively from medical records. RESULTS: The retrospective analysis revealed that the diagnosis of acromegaly was preceded by approximately 8.1+/-1.1 years of signs and symptoms of the disease. Forty-six of the 65 patients (71%) had macroadenomas, 16 (25%) had microadenomas, and the remaining three had empty sella. The rate of biochemical cure or remission was 81% for microadenoma (13/16), 64% for macroadenoma without extrasellar extension (9/14), and 13% for macroadenoma with cavernous sinus extension (2/15). Eighteen (28%) patients had impaired glucose tolerance (IGT) and 32 (49%) had diabetes mellitus (DM). After treatment for acromegaly, glucose metabolism was analyzed again in 38 patients, and it improved in 26 patients with IGT or DM. Twenty-five of 65 patients (38%) had hypertension. Of 26 patients who underwent barium enema or colonoscopy, 10 had colonic polyps and 4 had colon cancer. CONCLUSION: This study suggests that long-term excessive growth hormone (GH) secretion causes many complications. Therefore, awareness of the early symptoms and signs of acromegaly and long-term careful management of complications, along with therapy to reduce serum GH/insulin-like growth factor (IGF)-I levels, are important for patients with acromegaly.

Identification of human cancer-related genes by naturally occurring Hepatitis B Virus DNA tagging.

Proviral tagging has been used in animals as a powerful tool for cancer genetics. We show that a similar approach is possible in patients with hepatocellular carcinoma (HCC) infected by Hepatitis B Virus (HBV), a human pararetrovirus which may act by insertional mutagenesis. In this work, the HBV genome is used as a probe to identify cancer-related genes. By using HBV-Alu-PCR, we obtained 21 HBV/cellular DNA junctions from 18 different patients. In six of 21, we found the HBV DNA integrated into a cellular gene: (1) Sarco/Endoplasmic Reticulum Calcium ATPase1 Gene; (2) Thyroid Hormone Receptor Associated Protein 150 alpha Gene; (3) Human Telomerase Reverse Transcriptase Gene; (4) Minichromosome Maintenance Protein (MCM)-Related Gene; (5) FR7, a new gene expressed in human liver and cancer tissues; and (6) Nuclear Matrix Protein p84 Gene. Seven junctions contained unique cellular sequences. In the remaining eight, the HBV DNA was next to repetitive sequences, five of them of LINE1 type. The cellular genes targeted by HBV are key regulators of cell proliferation and viability. Our results show that studies on HBV-related HCCs allow to identify cellular genes involved in cancer. We therefore propose this approach as a valuable tool for functional cancer genomic studies in humans.

Effects of erbium,chromium:YSGG laser irradiation on canine mandibular bone.

BACKGROUND: Only relatively few reports have described the morphological effects on bone produced by erbium,chromium: yttrium,scandium,gallium,garnet (Er,Cr:YSGG) laser irradiation, and none has investigated the atomic changes or estimated the temperature increases involved. The objectives of this study were to investigate the morphological, atomic, and temperature changes in irradiated areas during and after laser irradiation, and to evaluate the cutting effect on canine mandibular bone in vitro. METHODS: Two canine mandibular bones were cut into 3 to 5 cm pieces and irradiated by an Er,Cr:YSGG laser utilizing a water-air spray at 5 W and 8 Hz for 10 or 30 seconds. During and after laser irradiation, temperature increases in the irradiated areas were measured by thermography. The samples were then observed by stereoscopy and scanning electron microscopy to determine morphological changes and by energy dispersive x-ray spectroscopy to evaluate atomic alterations. RESULTS: Regular holes or grooves having sharp edges and smooth walls were produced, but no melting or carbonization was observed. The maximum temperature increase was an average 12.6 degrees C for 30-second irradiation. The continuous time of a temperature increase of more than 10 degrees C was consistently less than 10 seconds. An atomic analytical examination revealed that the calcium:phosphorus ratio was not significantly changed between the lased and unlased areas (P>0.0 1). CONCLUSION: These results showed that the Er,Cr:YSGG laser cuts canine mandibular bone effectively without burning, melting, or altering the calcium:phosphorus ratio of the irradiated bone.

Development of a real-time hand dose monitor for personnel in interventional radiology.

Medical procedures denoted as interventional radiology require operation near an X ray beam, which brings high dose exposures to the operators' hands. For the effectual control of their extremity doses, a prototype of a real-time wrist dosemeter has been developed, hand dose monitor (HDM), based on a single silicon detector. Experiments were performed to test its response to diagnostic X rays. The HDM was highly sensitive and showed a linear response down to doses of a few tens of microsieverts. Though dose rate, energy and angular dependence of the response were observed in some extreme conditions, the HDM was proved to be of practical use if it was appropriately calibrated. Since an HDM enables personnel to check their hand doses on a real-time basis, it would enable medical staff to control the exposure themselves.

Effects of augmented delivery of pyruvate on myocardial high-energy phosphate metabolism at high workstate.

This study was performed to determine whether the fall in myocardial high-energy phosphates (HEP) that occurs during high workstates can be ascribed to either inadequate glycolytic pyruvate generation and conversion to acyl-CoA or limitation of long-chain fatty acid transport into the mitochondria. This was tested by using infusions of either pyruvate or butyrate in anesthetized dogs. Pyruvate was used because it bypasses the glycolytic sequence of reactions, activates pyruvate dehydrogenase, and increases mitochondrial NADH concentration ([NADH(m)]) in isolated myocardium, whereas butyrate enters the mitochondria without need for transport by the rate-limiting, palmitoyl-carnitine transporter. Increasing blood pyruvate from 0.16 +/- 0.016 mM to >3 mM did not alter baseline HEP levels determined with (31)P nuclear magnetic resonance, but caused an increase in the rate-pressure product and a modest increase in myocardial oxygen consumption (MVO(2)). Infusion of dobutamine + dopamine (each 20 microg x kg(-1) x min(-1) iv) increased MVO(2) and caused decreases of myocardial phosphocreatine (PCr)/ATP. Pyruvate partially reversed the decrease of HEP levels produced by catecholamine stimulation, whereas butyrate had no effect. Neither pyruvate nor butyrate caused an increase of MVO(2) during catecholamine infusion. Deoxymyoglobin was not detected by (1)H magnetic resonance spectroscopyy in any group. The data demonstrate that carbon substrate availability to the mitochondria is not the only cause of the reduction of PCr/ATP that occurs at high workstates. Supplemental pyruvate (but not butyrate) attenuated the reduction of PCr/ATP during the high workstates; this may have resulted from direct effects on intermediary metabolism or from other effects such as the free radical scavenging activity of pyruvate.

Effects of erbium, chromium:YSGG laser irradiation on root surface: morphological and atomic analytical studies.

OBJECTIVE: The purpose of this study was to investigate the morphological and atomic changes on the root surface by stereoscopy, field emission-scanning electron microscopy (FE-SEM), and energy dispersive X-ray spectroscopy (SEM-EDX) after erbium, chromium:yttrium, scandium, gallium, garnet (Er,Cr:YSGG) laser irradiation in vitro. SUMMARY BACKGROUND DATA: There have been few reports on morphological and atomic analytical study on root surface by Er,Cr:YSGG laser irradiation. METHODS: Eighteen extracted human premolar and molar teeth were irradiated on root surfaces at a vertical position with water-air spray by an Er,Cr:YSGG laser at the parameter of 5.0 W and 20 Hz for 5 sec while moving. The samples were then morphologically observed by stereoscopy and FE-SEM and examined atomic-analytically by SEM-EDX. RESULTS: Craters having rough but clean surfaces and no melting or carbonization were observed in the samples. An atomic analytical examination showed that the calcium ratio to phosphorus showed no significant changes between the control and irradiated areas (p > 0.01). CONCLUSIONS: These results showed that the Er,Cr:YSGG laser has a good cutting effect on root surface and causes no burning or melting after laser irradiation.

Roles and mechanisms of action of pituitary adenylate cyclase-activating polypeptide (PACAP) in growth hormone and prolactin secretion.

It appears that PACAP has a direct action on somatotrophs to release GH. The intracellular signal transduction mechanisms for PACAP might be similar to but partly distinct from those for GRH. PACAP might play a role in GH secretion induced by serotoninergic mechanisms but not in ultradian rhythm of GH secretion in the rat. PACAP can stimulate PRL release from the pituitary in rats possibly through indirect paracrine effect. In addition, PACAP might participate in regulation of PRL secretion via hypothalamic VIP.

Analysis of surface roughness of enamel and dentin after Er,Cr:YSGG laser irradiation.

OBJECTIVE: The purpose of this investigation was to compare the surface roughness of enamel and dentin following the Er,Cr:YSGG laser irradiation and acid etching. BACKGROUND DATA: Laser-roughened enamel or dentin surfaces have been expected to enhance restorative materials bond strength. MATERIALS AND METHODS: Er,Cr:YSGG laser irradiation was performed in one half of each polished enamel or dentin sample at 3 W (33.9 J/cm2, with air 70% and water 20%,) pulse energy for 6 sec. Then the other half was treated with 37% phosphoric acid for 30 sec. Surface roughness and morphological studies were performed. RESULTS: It was found that surface roughness was significantly increased with the laser system. Scanning electron microscopy analysis showed that irradiated surface produces a rough surface that was completely lacking of a smear layer; there was also no cracking of enamel or dentin. CONCLUSION: Er,Cr:YSGG laser irradiation could provide an effective and alternative method to the acid etch technique.

Protective effect of Oren-gedoku-to (Huang-Lian-Jie-Du-Tang) against impairment of learning and memory induced by transient cerebral ischemia in mice.

The protective effect of Oren-gedoku-to (OGT; Huang-Lian-Jie-Du-Tang), a traditional Chinese medicine, against impairment of learning and memory induced by transient cerebral ischemia was investigated in mice. The cerebral ischemia caused a reduction of step-down latency and an increase of step-down errors in the passive avoidance task. Pretreatment with oral administration of OGT (2, 4 or 8 g of herbs per kg) once daily for 5 days prolonged the step-down latency significantly and decreased the step-down errors as compared with those of sham-operated controls. In the Morris water maze test, the cerebral ischemia caused an increase in the latency until finding the platform in the training trial and a decrease in the percentage of swimming in the quadrant of the former platform in the probe trial. Oren-gedoku-to (OGT; 2, 4 and 8 g/kg, p. o.) shortened the latency of escaping markedly onto the platform in the training trial and increased the percentage of crossing the former platform quadrant in the probe trial. A reference drug, tacrine (0.5 and 1.0 mg/kg, p.o.), prevented the reduction of step-down latency in the passive avoidance task and shortened the escape latency in the Morris water maze task. Furthermore, OGT significantly protected against cerebral ischemia-induced reduction in the acetylcholine (ACh) content of the cerebral cortex, hippocampus and striatum. These results indicate that the protective effects of OGT against the impairment of learning and memory induced by transient cerebral ischemia may be associated with preventing the decrease in the ACh content of the mouse brain.

Carotenoids in human blood plasma after ingesting paprika juice.

We investigated the presence of different carotenoids in male human subject after the ingestion of paprika juice, and identified capsanthin, capsanthone, cucurbitaxanthin A, 11-cis-capsanthin, lutein and zeaxanthin in the human plasma. These results suggest that capsanthone and 11-cis-capsanthin might be as important as capsanthin for human health.

Therapeutic effect of oral levofloxacin, ciprofloxacin, and ampicillin on experimental murine pneumonia caused by penicillin intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations of the quinolones are similar.

The therapeutic efficacy of oral treatment with levofloxacin, ciprofloxacin, and ampicillin on an experimental pneumonia caused by the penicillin-intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations (MICs) of the quinolones are similar was assessed in immunocompetent CBA/J mice. Levofloxacin exhibited a dose-dependent therapeutic effect, and achieved complete eradication of S. pneumoniae from the lungs at 120 mg/kg/day, whereas ciprofloxacin and ampicillin were hardly effective at all. A pharmacokinetic study in infected mice revealed good oral absorption and lung tissue penetration of levofloxacin (peak lung concentration: 5.95 microg/g of lung), low oral absorption of ciprofloxacin in spite of a good penetration into lung tissue (1.10 microg/g of lung), and low lung tissue penetration of ampicillin despite rather good oral absorption (1.71 microg/g of lung). In an in vitro time-kill study that simulated the peak concentration of drugs in the lungs of infected animals, the killing activity of levofloxacin was found to be greater than that of ciprofloxacin and ampicillin. These data suggest that the therapeutic efficacy of levofloxacin in this model is attributable to both its potent bactericidal activity and excellent pharmacokinetic profile.

Myocardial creatine kinase kinetics in hearts with postinfarction left ventricular remodeling.

This study examined whether alterations in myocardial creatine kinase (CK) kinetics and high-energy phosphate (HEP) levels occur in postinfarction left ventricular remodeling (LVR). Myocardial HEP and CK kinetics were examined in 19 pigs 6 wk after myocardial infarction was produced by left circumflex coronary artery ligation, and the results were compared with those from 9 normal pigs. Blood flow (microspheres), oxygen consumption (MVO2), HEP levels [31P magnetic resonance spectroscopy (MRS)], and CK kinetics (31P MRS) were measured in myocardium remote from the infarct under basal conditions and during dobutamine infusion (20 micrograms. kg-1. min-1 iv). Six of the pigs with LVR had overt congestive heart failure (CHF) at the time of study. Under basal conditions, creatine phosphate (CrP)-to-ATP ratios were lower in all transmural layers of hearts with CHF and in the subendocardium of LVR hearts than in normal hearts (P < 0.05). Myocardial ATP (biopsy) was significantly decreased in hearts with CHF. The CK forward rate constant was lower (P < 0.05) in the CHF group (0.21 +/- 0.03 s-1) than in LVR (0.38 +/- 0.04 s-1) or normal groups (0.41 +/- 0.03 s-1); CK forward flux rates in CHF, LVR, and normal groups were 6.4 +/- 2.3, 14.3 +/- 2.1, and 20.3 +/- 2.4 micromol. g-1. s-1, respectively (P < 0.05, CHF vs. LVR and LVR vs. normal). Dobutamine caused doubling of the rate-pressure product in the LVR and normal groups, whereas CHF hearts failed to respond to dobutamine. CK flux rates did not change during dobutamine in any group. The ratios of CK flux to ATP synthesis (from MVO2) under baseline conditions were 10.9 +/- 1.2, 8. 03 +/- 0.9, and 3.86 +/- 0.5 for normal, LVR, and CHF hearts, respectively (each P < 0.05); during dobutamine, this ratio decreased to 3.73 +/- 0.5, 2.58 +/- 0.4, and 2.78 +/- 0.5, respectively (P = not significant among groups). These data demonstrate that CK flux rates are decreased in hearts with postinfarction LVR, but this change does not limit the response to dobutamine. In hearts with end-stage CHF, the changes in HEP and CK flux are more marked. These changes could contribute to the decreased responsiveness of these hearts to dobutamine.

Phytate and phosphorus movements in the digestive tract of horses.

This experiment was conducted to study phytate degradation and the effect of dietary phytate level on phosphorus absorption in the gastrointestinal tract of horses. Six Thoroughbred horses were fed diets containing low-phytate diet or high-phytate diet for 5 days. The diets were supplemented with Cr2O3 as an unabsorbable marker. The horses were killed 3 h after the last feeding and digesta in some segments of the intestine were collected. In both dietary groups, the daily passage of phytate phosphorus was decreased in the upper small intestine and in the lower large intestine. The daily passage of phytate phosphorus in the lower large intestine did not differ between these groups. Although the passage of total phosphorus increased in the upper small intestine and in the upper large intestine of both groups, its passage decreased in the lower large intestine. These results suggest that phytate phosphorus is degraded in the upper small intestine and in the lower large intestine of both groups. Phosphorus is suggested to be mainly absorbed in the lower large intestine. Therefore, phytate phosphorus is considered to be easily absorbed in horses because the major site of phosphorus is the lower large intestine where most of phytate is already degraded.

Effects of paeoniflorin derivatives on scopolamine-induced amnesia using a passive avoidance task in mice; structure-activity relationship.

Paeoniflorin (1) and its derivatives having in common a cage-like pinane skeleton with hemiketal-acetal system, were evaluated for their effects on memory impairment induced by scopolamine in mice using a step-down type passive avoidance task. In the test session, 1 and its derivatives were intraperitoneally (i.p.) administered at doses of 0.002, 0.01, 0.02 and 0.2 mmol/kg, and 30 min later (15 min before the experiment), scopolamine (1 mg/kg, i.p.) was given. These compounds showed dose-dependent attenuation in a dose range of 0.002-0.02 mmol/kg and also enhancement of scopolamine-induced decrease in step-down latency. The effects of these compounds, except that of 2',3',4',5'-O-tetraacetyl-3-O-methylpaeoniflorin (8), followed a bell-shaped dose response profile. 8-Debenzoyl-6-deglucosyl-3-O-methylpaeoniflorin (6) showed no significant increase in the step-down latency at all tested doses. Maximum step-down latency was obtained by 3-O-methylpaeoniflorin (3) and 2',3,3',4',5'-penta-O-methylpaeoniflorin (7) (the minimal effective dose was 0.002 mmol/kg). Relative to 3, debenzoylation, as in 8-debenzoyl-3-O-methylpaeoniflorin (4), slightly increased the latency, while deglucosylation, as in 6-deglucosyl-3-O-methylpaeoniflorin (5), significantly reduced the prolongation of latency. Removal of both glucose and benzoyl moieties resulted in the loss of activity as seen in 6. These results revealed that, in addition to the cage-like pinane skeleton, the benzoyl and the glucosyl moieties are important structural elements of the paeoniflorin skeleton as its effects on scopolamine-induced amnesia.