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2.
Endocr Res ; 38(1): 8-14, 2013.
Article in English | MEDLINE | ID: mdl-22594946

ABSTRACT

BACKGROUND: Both neuropeptide Y (NPY) and ghrelin can enhance the feeding behavior. The purpose of this study was to determine whether NPY and ghrelin are involved in hyperphagia and obesity induced by lesions of the hypothalamic paraventricular nucleus (PVN). METHODS: Sham-operated control rats and rats subjected to bilateral electrolytic lesions of the PVN were administered NPY (5 µg/rat) by intracerebroventricular infusion or ghrelin (20 µg/kg) by intraperitoneal (i.p.) injection. Control rats were administered the appropriate vehicle by the same route as the drug. We measured the cumulative food intake (FI) for 2 h after infusion of NPY and for 4 h after ghrelin injection. RESULTS: NPY significantly increased the cumulative FI in sham-operated rats. In PVN-lesioned rats, however, the cumulative FI at each time point (15 min, 30 min, 1 h, and 2 h) after NPY infusion was not significantly different from vehicle infusion, showing that NPY lost its orexigenic effect in PVN-lesioned rats. Following ghrelin injection, the cumulative FI was greater in PVN-lesioned rats than sham-operated rats, indicating that PVN lesions enhanced the orexigenic effects of ghrelin. CONCLUSION: These results suggest that the hyperphagia and obesity induced by PVN lesions may be related to an increased orexigenic action of ghrelin, but not NPY.


Subject(s)
Eating/drug effects , Neuropeptide Y/pharmacology , Paraventricular Hypothalamic Nucleus/physiology , Animals , Feeding Behavior/drug effects , Ghrelin/pharmacology , Male , Rats , Rats, Wistar
3.
J Hosp Infect ; 121: 9-13, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34915052

ABSTRACT

In infants with immunodeficiency, rotavirus (RV) vaccines can be continuously excreted in stool. We analysed nosocomial infection with RV vaccine strain in immunodeficient paediatric patients. RV1 RNAs were detected in stool and serum samples from case A, who was vaccinated with RV1, and case B, who was not. PAGE analysis of serial stool samples of case A revealed several rearrangements of the RV genome. In case B, the only band pattern detected was the same as a rearrangement detected in case A at the same time. In summary, RV vaccination of infants with immunodeficiency poses a risk of nosocomial infections.


Subject(s)
Cross Infection , Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Child , Cross Infection/prevention & control , Feces , Humans , Infant , Rotavirus/genetics , Rotavirus Infections/prevention & control , Rotavirus Vaccines/adverse effects , Vaccination
4.
Colorectal Dis ; 13(3): 302-7, 2011 Mar.
Article in English | MEDLINE | ID: mdl-19912288

ABSTRACT

AIM: To assess the feasibility and outcomes of reoperative laparoscopic-assisted surgery for recurrent Crohn's disease compared with index laparoscopic resections. METHOD: A retrospective analysis of a prospectively maintained database was performed from 2001 to 2008 on patients who had primary laparoscopy (group I) or reoperative laparoscopy for Crohn's disease (group II). Data collection included demographic and surgical data, and postoperative outcomes. RESULTS: One hundred and thirty patients were included in this study, distributed as follows: group I, 80 patients with a mean age of 35 years; and group II, 50 patients with a mean age of 42 years. Preoperative American Society of Anesthesiologists score and body mass index were similar in both groups. Patients in group II had a longer period of disease (15.5 vs 8.9 years in groups I and II, respectively; P = 0.0002). Immunosuppressive therapy had been utilized in 66 (82.5%) and in 42 (84%) patients in groups I and II, respectively. Ileocolic resection was the most commonly performed procedure in both groups (82%), followed by subtotal colectomy. Conversion rates were 18.7 and 32% in groups I and II, respectively (P = 0.09). The mean operative time (182 vs 201 min) and mean blood loss (161 vs 202 ml) were not significantly different (P > 0.05); however, the overall incisional length was significantly longer in group II (6.7 vs 11.4 cm, P = 0.045). A stoma was created in 17 and 16% of patients in groups I and II, respectively. Overall, early postoperative complications were not statistically significantly different between the two groups (P > 0.05); anastomotic leak occurred in four (5%) and one (2%) patients (P = 0.65), and abdominal abscess in three (3.75%) and four (8%) patients (P = 0.56), in groups I and II, respectively. Reoperative rates were 10 and 6% (P = 0.53), and mean hospital stay was similar in groups I and II respectively (6.7 vs 7.5 days, respectively; P = 0.3266). There was no mortality. CONCLUSION: The results of laparoscopic-assisted resection for recurrent Crohn's disease are similar to those for primary resection.


Subject(s)
Colon/surgery , Crohn Disease/surgery , Ileum/surgery , Laparoscopy/adverse effects , Reoperation/adverse effects , Surgical Stomas , Abdominal Abscess/etiology , Adult , Anastomotic Leak/etiology , Colectomy , Crohn Disease/complications , Humans , Laparoscopy/methods , Male , Middle Aged , Recurrence , Reoperation/methods , Retrospective Studies , Treatment Outcome , Young Adult
5.
Occup Med (Lond) ; 60(3): 231-3, 2010 May.
Article in English | MEDLINE | ID: mdl-19951997

ABSTRACT

BACKGROUND: The mental health of nurses is an important issue. AIMS: To examine relationships between effort-reward imbalance (ERI) and depression and anxiety in nurses of a Japanese general hospital. METHODS: A self-report survey was conducted among 406 nurses. Work stress was measured using a Japanese version of the ERI scale. Depression and anxiety were assessed by an item of the QOL-26. Logistic regression analysis was used to determine the independent contribution of the effort-reward ratios or overcommitment to the depressive state. RESULTS: Both higher effort-money ratio and higher overcommitment significantly correlated with the depressive state (OR: 2.75; 95% CI: 1.34-5.66 and OR: 1.27; 95% CI: 1.15-1.41, respectively). CONCLUSIONS: These findings suggest that in addition to effort-money ratio, overcommitment at work is an especially important issue that may be able to be managed in health promotion services for nurses in general hospitals.


Subject(s)
Anxiety/psychology , Depression/psychology , Nursing Staff, Hospital/psychology , Occupational Diseases/psychology , Reward , Stress, Psychological/psychology , Adult , Attitude of Health Personnel , Hospitals, General , Humans , Japan/epidemiology , Logistic Models , Middle Aged , Models, Psychological , Self Report , Workload/psychology
6.
Oncology ; 77(3-4): 192-6, 2009.
Article in English | MEDLINE | ID: mdl-19729976

ABSTRACT

OBJECTIVE: To determine the efficacy and tolerability of oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced colorectal cancer. METHODS: S-1 was administered orally at 80 mg/m(2)/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at a dose of 80 mg/m(2)/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 282 courses of treatment were administered to 40 patients, achieving complete response in 1 and partial responses in 24 with an overall response rate of 62.5% (95% CI: 47.5-77.5%). Median progression-free survival was 7.8 months (95% CI: 6.7-9.6 months). The rates of grade 3 or 4 toxicities were as follows: neutropenia 12.5%, anorexia 12.5%, fatigue 10%, and diarrhea 7.5%. CONCLUSION: Combined treatment with S-1 and irinotecan is an effective, well-tolerated and convenient regimen in patients with advanced colorectal cancer which is easily maintained.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Capecitabine , Colorectal Neoplasms/mortality , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Combinations , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Irinotecan , Male , Middle Aged , Oxonic Acid/administration & dosage , Oxonic Acid/adverse effects , Tegafur/administration & dosage , Tegafur/adverse effects
7.
Kyobu Geka ; 62(2): 136-9, 2009 Feb.
Article in Japanese | MEDLINE | ID: mdl-19202935

ABSTRACT

A rare case of recurrent Castleman disease is reported. A 49-year-old man was referred to our division under the suspicion of mediastinal tumor. We performed tumor resection successfully, and the tumor was shown to be Castleman disease by histology. The patient had a past history of this disease, therefore it was suggested that the tumor recurred at the same site 20-years after removal.


Subject(s)
Castleman Disease/diagnosis , Castleman Disease/surgery , Castleman Disease/pathology , Humans , Male , Middle Aged , Recurrence , Time Factors
8.
Kyobu Geka ; 62(7): 560-3, 2009 Jul.
Article in Japanese | MEDLINE | ID: mdl-19588827

ABSTRACT

A 77-year-old woman was transferred as traumatic thoracic aortic dissection with subarachnoid hemorrhage soon after a traffic accident. Her consciousness was slightly compromised and cardiogenic shock was developed. Serial computed tomography (CT) scans revealed an unchanging subarachnoid hemorrhage and a progressive mediastinal hemorrhage and pericardial effusion due to traumatic type B aortic dissection. An emergency distal arch replacement was performed under cardiopulmonary bypass 4 hours after the injury. She woke up 3 days after the operation without progression of subarachnoid hemorrhage on a cerebral CT scan. She was discharged 36 days after the injury.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Subarachnoid Hemorrhage/complications , Thoracic Injuries/complications , Accidents, Traffic , Aged , Aortic Dissection/etiology , Aortic Aneurysm, Thoracic/etiology , Emergencies , Female , Humans , Subarachnoid Hemorrhage/etiology
9.
Oncogene ; 26(34): 4969-78, 2007 Jul 26.
Article in English | MEDLINE | ID: mdl-17310998

ABSTRACT

To investigate the mechanism by which HSulf-1 expression is downregulated in ovarian cancer, DNA methylation and histone acetylation of HSulf-1 was analysed in ovarian cancer cell lines and primary tumors. Treatment of OV207 and SKOV3 by 5-aza-2'-deoxycytidine resulted in increased transcription of HSulf-1. Sequence analysis of bisulfite-modified genomic DNA from ovarian cell lines and primary tumors without HSulf-1 expression revealed an increase in the frequency of methylation of 12 CpG sites in exon 1A. Chromatin immunoprecipitation assays showed an increase in histone H3 methylation in cell lines without HSulf-1 expression. To assess the significance of HSulf-1 downregulation in ovarian cancer, OV167 and OV202 cells were transfected with HSulf-1 siRNA. Downregulation of HSulf-1 expression in OV167 and OV202 cells lead to an attenuation of cisplatin-induced cytotoxicity. Moreover, patients with ovarian tumors expressing higher levels of HSulf-1 showed a 90% response rate (27/30) to chemotherapy compared to a response rate of 63% (19/30) in those with weak or moderate levels (P=0.0146, chi(2) test). Collectively, these data indicate that HSulf-1 is epigenetically silenced in ovarian cancer and that epigenetic therapy targeting HSulf-1 might sensitize ovarian tumors to conventional first-line therapies.


Subject(s)
Drug Resistance, Neoplasm/genetics , Epigenesis, Genetic , Gene Silencing , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Sulfotransferases/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/toxicity , Azacitidine/analogs & derivatives , Azacitidine/pharmacology , Cell Line, Tumor , Chromatin/metabolism , Cisplatin/toxicity , CpG Islands , DNA Methylation , Decitabine , Enzyme Inhibitors/pharmacology , Female , Gene Expression Regulation, Neoplastic , Histone Deacetylase Inhibitors , Humans , Middle Aged , Ovarian Neoplasms/enzymology , Sulfotransferases/metabolism
10.
Neuroscience ; 146(1): 123-34, 2007 Apr 25.
Article in English | MEDLINE | ID: mdl-17320303

ABSTRACT

Ca2+-induced Ca2+ release (CICR) occurs via activation of ryanodine receptors (RyRs) in frog motor nerve terminals after RyRs are primed for activation by repetitive Ca2+ entries, thereby contributing to synaptic plasticity. To clarify how the mechanism of CICR becomes activable by repetitive Ca2+ entries, we studied effects of a RyR modulator, cyclic ADP-ribose (cADPr), on CICR by Ca2+ imaging techniques. Use-dependent binding of fluorescent ryanodine and its blockade by ryanodine revealed the existence of RyRs in the terminals. Repetition of tetani applied to the nerve produced repetitive rises in intracellular Ca2+ ([Ca2+]i) in the terminals. The amplitude of each rise slowly waxed and waned during the course of the stimulation. These slow rises and decays were blocked by ryanodine, indicating the priming, activation and inactivation of CICR. Uncaging of caged-cADPr loaded in the terminals increased the amplitude of short tetanus-induced rises in [Ca2+]i and the amplitude, time to peak and half decay time of the slow waxing and waning rises in [Ca2+]i evoked by repetitive tetani. A cADPr blocker, 8-amino-cADPr, loaded in the terminals decreased the slow waxing and waning component of rises and blocked all the actions of exogenous cADPr. It is concluded that cADPr enhances the priming and activation of CICR. The four-state model for RyRs suggests that cADPr inhibits the inactivation of CICR and increases the activation efficacy of RyR.


Subject(s)
Calcium/metabolism , Cyclic ADP-Ribose/analogs & derivatives , Motor Neurons/cytology , Presynaptic Terminals/drug effects , Presynaptic Terminals/metabolism , Animals , Cyclic ADP-Ribose/pharmacology , In Vitro Techniques , Motor Neurons/drug effects , Neuromuscular Junction/cytology , Ranidae , Ryanodine/metabolism , Time Factors
11.
Oncology ; 72(1-2): 58-63, 2007.
Article in English | MEDLINE | ID: mdl-17998791

ABSTRACT

PURPOSE: To determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan plus S-1 in advanced colorectal cancer. PATIENTS AND METHODS: S-1 was administered orally at 80 mg/m2/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 60 mg/m2/day, stepping up to 80, 100, 120 or 140 mg/m2/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 20 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 100 mg/m2, because 2 of 3 patients developed dose-limiting toxicities, such as anorexia, fatigue and diarrhea. Therefore, the recommended dose of CPT-11 was set at 80 mg/m2. Tumor responses were seen in 8 of 14 patients with measurable lesions. CONCLUSION: A combination of S-1 with CPT-11 is safe and can be recommended for further phase II studies in patients with advanced colorectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/drug therapy , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Drug Combinations , Female , Humans , Irinotecan , Male , Maximum Tolerated Dose , Middle Aged , Oxonic Acid/administration & dosage , Tegafur/administration & dosage
12.
Exp Clin Endocrinol Diabetes ; 115(10): 669-73, 2007 Nov.
Article in English | MEDLINE | ID: mdl-18058602

ABSTRACT

Bilateral lesions of the hypothalamic paraventricular nuclei (PVN) induce hyperphagia and obesity, and ghrelin stimulates appetite in rodents and humans. Conversely, corticotrophin-releasing hormone (CRH) and melanotan-II (MT-II, a synthetic structural homologue of alpha-melanocyte-stimulating hormone, alphaMSH) inhibit feeding behavior. The purpose of the present study was to determine whether these peptides are involved in the hyperphagia and obesity induced by PVN lesions. After bilateral electrolytic lesions of the PVN, rats were given ghrelin intraperitoneally (i. p.), or intracerebroventricular (i. c. v.) infusion of CRH or MT-II. We measured the cumulative food intake (FI) for 4 h after ghrelin injection in rats fed AD LIB, and the changes in FI at 15 min, 30 min, 1 h, and 2 h after infusion of CRH and MT-II in rats fasted for 24 h. Ghrelin significantly increased cumulative FI, with maximal response 3 h and 4 h after injection, and at these times, the FI of PVN-lesioned rats was greater than that of sham-operated rats. CRH significantly decreased FI in all experimental animals, but at 1 h, there was a more powerful inhibitory effect on FI in the PVN-lesioned group than in the sham-operated group. MT-II decreased FI in sham-operated, but not in PVN-lesioned rats. Thus, ghrelin and CRH showed more potent orexigenic and anorectic effects in PVN-lesioned rats, respectively, but MT-II lost its inhibitory action on feeding behavior. These results suggest that the hyperphagia and obesity induced by PVN lesions may be related to an increased orexigenic action of ghrelin due to the destruction of endogenous CRH and alphaMSH receptors.


Subject(s)
Anticarcinogenic Agents/pharmacology , Corticotropin-Releasing Hormone/pharmacology , Eating/drug effects , Ghrelin/pharmacology , Hormones/pharmacology , Paraventricular Hypothalamic Nucleus , alpha-MSH/analogs & derivatives , Animals , Fasting , Hyperphagia/drug therapy , Hyperphagia/etiology , Male , Obesity/drug therapy , Obesity/etiology , Paraventricular Hypothalamic Nucleus/pathology , Rats , Rats, Wistar , Time Factors , alpha-MSH/pharmacology
13.
Acta Radiol ; 48(9): 1032-7, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17957522

ABSTRACT

BACKGROUND: The usefulness of fast fluid-attenuated inversion-recovery (FLAIR) sequences after administration of contrast medium (f-FLAIR (+)) has been shown in depicting brain tumors including metastases and meningeal carcinomatosis. Contrast-enhanced multi-shot echo-planar FLAIR (Ms-EPI-FLAIR (+)), comprising combined sequences of f-FLAIR (+) and Ms-EPI, may provide the advantages of f-FLAIR (+) along with rapid acquisition. PURPOSE: To compare Ms-EPI-FLAIR (+) with post-contrast spin-echo T1-weighted imaging (SE-T1WI (+)) in the depiction of brain metastases. MATERIAL AND METHODS: In 14 patients with metastatic tumors of the brain, spin-echo precontrast T1-weighted imaging (SE-T1WI (-)), fast spin-echo T2-weighted imaging (FSE-T2WI), fast-FLAIR, SE-T1WI (+), and Ms-EPI-FLAIR (+) were acquired. For qualitative evaluation of SE-T1WI (+) and Ms-EPI-FLAIR (+), receiver operating characteristic (ROC) analysis was performed in two different readers. For quantitative analysis, the intensity ratios (intensity of tumor divided by intensity of peritumoral region) in SE-T1WI (+) and Ms-EPI-FLAIR (+) were compared. RESULTS: Although pre-contrast f-FLAIR detected 84 of 106 tumors, Ms-EPI-FLAIR (+) detected 98 of 106 tumors. In the ROC analysis for observers A and B, Az values in SE-T1WI (+) did not differ from values in Ms-EPI-FLAIR (+). Quantitatively, the intensity ratio in Ms-EPI-FLAIR (+) also did not differ from that in SE-T1WI (+). CONCLUSION: Detectability of brain metastases with Ms-EPI-FLAIR (+) is almost similar to that with SE-T1WI (+). Ms-EPI-FLAIR (+) could be an alternative to SE-T1WI (+) in the depiction of brain metastases.


Subject(s)
Brain Neoplasms/secondary , Contrast Media , Echo-Planar Imaging/methods , Gadolinium DTPA , Magnetic Resonance Imaging/methods , Aged , Female , Humans , Image Enhancement/methods , Male , Middle Aged , ROC Curve
14.
Water Sci Technol ; 56(1): 71-80, 2007.
Article in English | MEDLINE | ID: mdl-17711001

ABSTRACT

Verification of a diffuse pollution model involves comparing results actually observed with those predicted by precise model inputs. Acquisition of precise model inputs is, however, problematic. In particular, when the target catchment is large and substantial estimation uncertainty exists, not only model verification but also prediction is difficult. Therefore, in this study, rice-farming data were collected for all paddy fields from all farmers in a catchment and pesticide adsorption and degradation rates in paddy field soil samples were measured to obtain precise model inputs. The model inputs successfully verified the model's capability to predict pesticide concentrations in river water. Sensitivity analyses of the model inputs elucidated the processes significantly affecting pesticide runoff from rice farms. Pesticide adsorption and degradation rates of the soil did not significantly affect pesticide concentrations, although pesticide discharge to river water accounted for less than 50% of the total quantity of pesticide applied to fields, possibly owing to pesticide adsorption and degradation. The timing of increases in pesticide concentrations in river water was affected mostly by the farming schedule, including the time of pesticide application and irrigation, and secondarily by rainfall events.


Subject(s)
Agriculture , Models, Biological , Pesticides/analysis , Pesticides/chemistry , Water Pollutants, Chemical/analysis , Water/chemistry , Adsorption , Diffusion , Japan , Soil Pollutants/chemistry , Soil Pollutants/metabolism , Thiophenes/chemistry , Water Pollutants, Chemical/chemistry
15.
Bone Joint Res ; 6(2): 108-112, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28246094

ABSTRACT

OBJECTIVES: The surface of pure titanium (Ti) shows decreased histocompatibility over time; this phenomenon is known as biological ageing. UV irradiation enables the reversal of biological ageing through photofunctionalisation, a physicochemical alteration of the titanium surface. Ti implants are sterilised by UV irradiation in dental surgery. However, orthopaedic biomaterials are usually composed of the alloy Ti6Al4V, for which the antibacterial effects of UV irradiation are unconfirmed. Here we evaluated the bactericidal and antimicrobial effects of treating Ti and Ti6Al4V with UV irradiation of a lower and briefer dose than previously reported, for applications in implant surgery. MATERIALS AND METHODS: Ti and Ti6Al4V disks were prepared. To evaluate the bactericidal effect of UV irradiation, Staphylococcus aureus 834 suspension was seeded onto the disks, which were then exposed to UV light for 15 minutes at a dose of 9 J/cm2. To evaluate the antimicrobial activity of UV irradiation, bacterial suspensions were seeded onto the disks 0, 0.5, one, six, 24 and 48 hours, and three and seven days after UV irradiation as described above. In both experiments, the bacteria were then harvested, cultured, and the number of colonies were counted. RESULTS: No colonies were observed when UV irradiation was performed after the bacteria were added to the disks. When the bacteria were seeded after UV irradiation, the amount of surviving bacteria on the Ti and Ti6Al4V disks decreased at 0 hours and then gradually increased. However, the antimicrobial activity was maintained for seven days after UV irradiation. CONCLUSION: Antimicrobial activity was induced for seven days after UV irradiation on both types of disk. Irradiated Ti6Al4V and Ti had similar antimicrobial properties.Cite this article: T. Itabashi, K. Narita, A. Ono, K. Wada, T. Tanaka, G. Kumagai, R. Yamauchi, A. Nakane, Y. Ishibashi. Bactericidal and antimicrobial effects of pure titanium and titanium alloy treated with short-term, low-energy UV irradiation. Bone Joint Res 2017;6:108-112. DOI: 10.1302/2046-3758.62.2000619.

16.
Water Sci Technol ; 53(10): 173-81, 2006.
Article in English | MEDLINE | ID: mdl-16838701

ABSTRACT

To predict rice-farming pesticide concentrations in river water with imprecise model inputs for screening-level analysis, a basin-scale runoff model was developed. The Monte Carlo method was applied to create estimates of input data regarding agricultural work schedules and parameters for pesticide decomposition and sorption in solids and water. The prediction accuracy of the model was evaluated when used with non-optimised pesticide parameters; the model was calibrated using hydrological data alone without reference to observed pesticide concentration data. Overall, predictions for the pesticide concentrations were successful within order-of-magnitude accuracy. The pesticide rankings according to the predicted concentration roughly agreed with those observed. The success of screening-level analysis indicates that the model prediction can help in selection of pesticides to be monitored and in determining the monitoring schedule for the river basin.


Subject(s)
Models, Theoretical , Oryza , Pesticides/analysis , Rivers/chemistry , Water Pollutants, Chemical/analysis , Agriculture , Environmental Monitoring , Water Movements , Water Pollution
17.
Biochim Biophys Acta ; 624(1): 218-25, 1980 Jul 24.
Article in English | MEDLINE | ID: mdl-7407235

ABSTRACT

By affinity chromatography on a concanavalin A-Sepharose column and gel filtration on a Sephadex G-25 column, a glycopeptide of 16 amino acid residues has been separated from a tryptic digest of reduced and carboxymethylated bovine rhodopsin. The glycopeptide was treated with cyanogen bromide and products were subjected to high-voltage paper electrophoresis. N-Blocked homoserine separated was reacted first with anhydrous hydrazine and then with dansyl chloride. The product was identified by thin-layer chromatography to be 1-acetyl-2-dansyl hydrazine, thus showing that the N-terminal blocking group was an acetyl group. The remaining peptide after cyanogen bromide treatment was partially sequenced by the Edman dansylation method. The present results and previously reported findings on the binding site of the sugar moiety, taken together, indicate that the N-terminal heptapeptide has the following structure: acetylMet-Asn(carbohydrate)-Gly-Thr-Glx-Gly-Pro.


Subject(s)
Methionine/analogs & derivatives , Retinal Pigments/analysis , Rhodopsin/analysis , Amino Acid Sequence , Amino Acids/analysis , Animals , Cattle , Chromatography, Affinity/methods , Concanavalin A , Glycopeptides/isolation & purification , Methionine/isolation & purification
18.
J Gen Physiol ; 112(5): 593-609, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9806968

ABSTRACT

The extent to which Ca2+-induced Ca2+ release (CICR) affects transmitter release is unknown. Continuous nerve stimulation (20-50 Hz) caused slow transient increases in miniature end-plate potential (MEPP) frequency (MEPP-hump) and intracellular free Ca2+ ([Ca2+]i) in presynaptic terminals (Ca2+-hump) in frog skeletal muscles over a period of minutes in a low Ca2+, high Mg2+ solution. Mn2+ quenched Indo-1 and Fura-2 fluorescence, thus indicating that stimulation was accompanied by opening of voltage-dependent Ca2+ channels. MEPP-hump depended on extracellular Ca2+ (0.05-0.2 mM) and stimulation frequency. Both the Ca2+- and MEPP-humps were blocked by 8-(N, N-diethylamino)octyl3,4,5-trimethoxybenzoate hydrochloride (TMB-8), ryanodine, and thapsigargin, but enhanced by CN-. Thus, Ca2+-hump is generated by the activation of CICR via ryanodine receptors by Ca2+ entry, producing MEPP-hump. A short interruption of tetanus (<1 min) during MEPP-hump quickly reduced MEPP frequency to a level attained under the effect of TMB-8 or thapsigargin, while resuming tetanus swiftly raised MEPP frequency to the previous or higher level. Thus, the steady/equilibrium condition balancing CICR and Ca2+ clearance occurs in nerve terminals with slow changes toward a greater activation of CICR (priming) during the rising phase of MEPP-hump and toward a smaller activation during the decay phase. A short pause applied after the end of MEPP- or Ca2+-hump affected little MEPP frequency or [Ca2+]i, but caused a quick increase (faster than MEPP- or Ca2+-hump) after the pause, whose magnitude increased with an increase in pause duration (<1 min), suggesting that Ca2+ entry-dependent inactivation, but not depriming process, explains the decay of the humps. The depriming process was seen by giving a much longer pause (>1 min). Thus, ryanodine receptors in frog motor nerve terminals are endowed with Ca2+ entry-dependent slow priming and fast inactivation mechanisms, as well as Ca2+ entry-dependent activation, and involved in asynchronous exocytosis. Physiological significance of CICR in presynaptic terminals was discussed.


Subject(s)
Calcium/metabolism , Calcium/pharmacology , Exocytosis/physiology , Motor Neurons/cytology , Presynaptic Terminals/metabolism , Action Potentials/physiology , Animals , Calcium Channel Blockers/pharmacology , Chelating Agents/pharmacology , Egtazic Acid/analogs & derivatives , Egtazic Acid/pharmacology , Evoked Potentials, Motor/drug effects , Evoked Potentials, Motor/physiology , Exocytosis/drug effects , Fluorescent Dyes , Gallic Acid/analogs & derivatives , Gallic Acid/pharmacology , Ion Channel Gating/drug effects , Ion Channel Gating/physiology , Magnesium/pharmacology , Motor Neurons/chemistry , Motor Neurons/metabolism , Neurotransmitter Agents/metabolism , Presynaptic Terminals/chemistry , Presynaptic Terminals/drug effects , Ranidae , Ryanodine Receptor Calcium Release Channel/metabolism , Time Factors
19.
J Gen Physiol ; 115(4): 519-32, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10736317

ABSTRACT

Ca(2+)-induced Ca(2+) release (CICR) enhances a variety of cellular Ca(2+) signaling and functions. How CICR affects impulse-evoked transmitter release is unknown. At frog motor nerve terminals, repetitive Ca(2+) entries slowly prime and subsequently activate the mechanism of CICR via ryanodine receptors and asynchronous exocytosis of transmitters. Further Ca(2+) entry inactivates the CICR mechanism and the absence of Ca(2+) entry for >1 min results in its slow depriming. We now report here that the activation of this unique CICR markedly enhances impulse-evoked exocytosis of transmitter. The conditioning nerve stimulation (10-20 Hz, 2-10 min) that primes the CICR mechanism produced the marked enhancement of the amplitude and quantal content of end-plate potentials (EPPs) that decayed double exponentially with time constants of 1.85 and 10 min. The enhancement was blocked by inhibitors of ryanodine receptors and was accompanied by a slight prolongation of the peak times of EPP and the end-plate currents estimated from deconvolution of EPP. The conditioning nerve stimulation also enhanced single impulse- and tetanus-induced rises in intracellular Ca(2+) in the terminals with little change in time course. There was no change in the rate of growth of the amplitudes of EPPs in a short train after the conditioning stimulation. On the other hand, the augmentation and potentiation of EPP were enhanced, and then decreased in parallel with changes in intraterminal Ca(2+) during repetition of tetani. The results suggest that ryanodine receptors exist close to voltage-gated Ca(2+) channels in the presynaptic terminals and amplify the impulse-evoked exocytosis and its plasticity via CICR after Ca(2+)-dependent priming.


Subject(s)
Calcium Channels/metabolism , Exocytosis/physiology , Neuronal Plasticity/physiology , Presynaptic Terminals/metabolism , Ryanodine Receptor Calcium Release Channel/metabolism , Animals , Calcium/metabolism , Electric Stimulation , Electrophysiology , In Vitro Techniques , Motor Endplate/metabolism , Motor Neurons/metabolism , Muscle, Skeletal/innervation , Muscle, Skeletal/metabolism , Neurotransmitter Agents/metabolism , Ranidae
20.
J Cereb Blood Flow Metab ; 20(1): 74-81, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10616795

ABSTRACT

To investigate the chronic effects of a novel thyrotropin-releasing hormone analog, JTP-2942 (N(alpha)-[(1S, 2R)-2-methyl-4-oxocyclopentylcarbonyl]-L-histidyl-L-prolinamide monohydrate), on behavioral changes after stroke, the authors examined its effects on motor and neurologic deficits using a middle cerebral artery (MCA) occlusion model in rats. A left MCA was permanently occluded at a proximal site. From 1 week after occlusion, JTP-2942 was intravenously administered once a day for 4 weeks. Sensorimotor performance was evaluated weekly for 10 weeks after the occlusion. The ability of the rat to maintain its body position on an inclined plane and neurologic examination based on hemiparesis and abnormal posture were examined. After all behavioral examinations were completed, the degree of shrinkage of the left hemisphere was measured. The ability of MCA-occluded rats to maintain body position on an inclined plane in the left-headed position was significantly lower than that of sham-operated rats throughout the test period. JTP-2942 gradually improved this deficit dose dependently, and a dose of 0.03 mg/kg of JTP-2942 significantly improved performance to the levels of the sham-operated rats. Neurologic deficits were also observed in MCA-occluded rats. JTP-2942 also significantly improved these deficits dose dependently. On the other hand, CDP-choline (500 mg/kg, administered intravenously), a therapeutic agent for the disturbance of consciousness and hemiparesis after stroke, improved neurologic deficits but did not affect the motor deficits measured using the inclined plane. It is noteworthy that the effects of JTP-2942 on these deficits were observed 4 weeks after cessation of drug administration. Furthermore, there was no difference in the degree of shrinkage of the cerebrum among the MCA-occluded groups. In the present study, long-lasting improving effects of JTP-2942 on the impairment of motor and neurologic functions were observed in rats with MCA occlusion, which continued after cessation of drug administration and which were not attributable to a reduction in ipsilateral cerebral shrinkage. It is considered that the effect of JTP-2942 on functional recovery is attributable to the activation of substitutive functions such as neuronal reconstruction. These pharmacologic properties of JTP-2942 may be of interest for the treatment of patients with motor and neurologic deficits during the chronic or subacute phase of stroke.


Subject(s)
Brain Ischemia/physiopathology , Motor Activity/drug effects , Thyrotropin-Releasing Hormone/analogs & derivatives , Animals , Avoidance Learning , Brain/drug effects , Brain/pathology , Brain Ischemia/psychology , Cerebral Infarction/pathology , Chronic Disease , Male , Nervous System/physiopathology , Rats , Rats, Wistar , Thyrotropin-Releasing Hormone/pharmacology
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