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1.
HLA ; 91(4): 302-303, 2018 04.
Article in English | MEDLINE | ID: mdl-29417749

ABSTRACT

HLA-B*40:333 differs from HLA-B*40:01:01 by a single nucleotide substitution at position 380 T>C.


Subject(s)
Alleles , HLA-B Antigens/genetics , Histocompatibility Testing/methods , Polymerase Chain Reaction/methods , Base Sequence , Exons/genetics , Genetic Loci , Humans , Sequence Alignment
2.
Eye (Lond) ; 27(7): 883-8, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23661155

ABSTRACT

PURPOSE: MicroRNA 34a (miR-34a) is involved in regulating tissue senescence. However, the role of miR-34a in age-related cataracts is unclear. In this study, we evaluated the correlations among the severity of lens opacity, patient age, and miR-34a expression level in the lens epithelium of age-related cataracts for clarifying the role of miR-34a in the lens senescence. METHODS: This study was carried as a case control study in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan. We recorded age of each patient at the time of their cataract surgery and information regarding lens opacity according to a modified version of the Lens Opacities Classification System III. Correlations among age, lens opacity, and miR-34a expression levels were evaluated. RESULTS: This study evaluated 110 patients with a mean age of 73.19 years (SD±10.2). Older patients had higher nuclear cataract (NC), cortical (C), and posterior subcapsular cataract (P) scores (one-way analysis of variance (ANOVA), P<0.05). miR-34a expression levels were significantly different between each age group (ANOVA post hoc Bonferroni's test, P<0.001), and there were moderate correlations between high NC, C, and P cataract scores and high miR-34a levels (Pearson correlation coefficient; R=0.606, 0.575, and 0.515, respectively). CONCLUSIONS: The current study demonstrated positive correlations between high miR-34a levels and high lens opacity severity in NC, C, or P cataracts. These results suggest that miR-34a expression has a role in lens senescence.


Subject(s)
Cataract/metabolism , Lens, Crystalline/metabolism , MicroRNAs/analysis , Aged , Aged, 80 and over , Analysis of Variance , Case-Control Studies , Cataract/pathology , Cohort Studies , Epithelium/metabolism , Female , Humans , Male , Middle Aged , Severity of Illness Index , Taiwan
3.
J. investig. allergol. clin. immunol ; 23(2): 112-119, mar.-abr. 2013. ilus
Article in English | IBECS | ID: ibc-111788

ABSTRACT

Introducción: Los organismos modificados genéticamente (GM) dan lugar a mejoras en la agricultura moderna relacionados con la eficiencia y beneficios de la producción de alimentos, sin embargo el potencial impacto de estos en la salud humana no ha sido clarificado. El motivo de este estudio fue investigar la alergenicidad entre el brócoli modificado genéticamente mediante isopenteniltransferasa frente al no modificado. Para ello se utilizó suero de pacientes alérgicos a brócoli para identificar la alergenicidad de ambos brócolis modificado o no modificado. Se estudió la unión de la IgE al brócoli de uno u otro tipo mediante inmunoblotting, ELISA y liberación de histamina. Resultados: Los resultados mostraron que el 7.2% de los pacientes tenían reacciones a brócoli (B. oleracea). La IgE específica a brócoli y la IgE total de los sujetos sensibilizados mostraban una correlación. Mediante Western blot observamos una heterogenia en la IgE en el suero de los pacientes reactiva frente a los componentes alergénicos. La alergenicidad de los brócolis, modificado o no modificado, no mostró diferencias significativas, lo cual indica que la trasformación del brócoli no afecta a su alergenicidad. Conclusiones: En nuestro estudio demostramos la ausencia de diferencias entre brócoli trasformado genéticamente o no (isopenteniltransferasa), por lo tanto no son esperables efectos sobre la alergenicidad en el brócoli transformado (AU)


Background: Genetically modified organisms (GMOs) provide modern agriculture with improvements in efficiency and the benefits of enhanced food production; however, the potential impact of GMOs on human health has not yet been clarified. Objective: To investigate the allergenicity of isopentenyltransferase (ipt)-transformed broccoli compared with non-GM broccoli. Methods: Sera from allergic individuals were used to identify the allergenicity of GM and non-GM broccoli. Immunoglobulin (Ig) binding of different lines of GM and non-GM broccoli was identifi ed using immunoblotting, enzyme-linked immunosorbent assay, and the histamine release assay. Results: Positive reactions to broccoli (Brassica Oleracea) were observed in 7.02% of individuals. Specific IgE to broccoli and total IgE from allergic individuals were well correlated. The different tests performed showed no significant differences in the allergenicity of conventionally raised and GM broccoli, indicating the absence of unexpected effects on allergenicity in ipt-transformed plants. Using Western blot analysis, we detected heterogeneous IgE-reactive allergenic components in broccoli-allergic sera, but no significant differences between GM and non-GM broccoli were observed in serum from the same patients. Conclusions: Our study demonstrates that there are no differences between GM (ipt-transformed) broccoli and non-GM broccoli, as determined by specific IgE in sera from broccoli-allergic patients. This indicates that there were no unexpected effects on allergenicity in this GM broccoli (AU)


Subject(s)
Humans , Food, Genetically Modified/adverse effects , Vegetables/adverse effects , Food Hypersensitivity/immunology , Plants, Genetically Modified/adverse effects , Risk Factors
4.
Eye (Lond) ; 24(8): 1359-65, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20379208

ABSTRACT

PURPOSES: The aims of this study were to describe the bacterial isolates and treatment outcomes of endophthalmitis after cataract surgery at a referral centre in Northern Taiwan. METHODS: This was a retrospective, interventional, and observational series. Medical records were review of patients with clinical diagnosed, and/or culture-proven bacterial endophthalmitis at a tertiary referral centre in Northern Taiwan from January 2002 to December 2008. Treatment generally conformed to standard guidelines. Main outcome measurements were results of organism culture, antibiotic susceptibility of isolated bacteria, and visual acuity (VA) outcome. RESULTS: Thirty-four patients had positive cultures. A total of 55.9% of the culture-positive isolates were Gram negative and 44.1% were Gram positive. Pseudomonas aeruginosa was the most commonly isolated organism. Eighteen patients had final VA better than 5/200, and 41 had final VA worse than 5/200. In multiple linear regression analysis, female gender, presence of hypopyon, and worse baseline VA were significant independent predictors of worse visual outcome. CONCLUSIONS: It was found that at a referral centre in Northern Taiwan, the majority of bacterial isolates were Gram negative in acute postoperative bacterial endophthalmitis after cataract surgery and P. aeruginosa was the most common bacterial isolate.


Subject(s)
Cataract Extraction/adverse effects , Endophthalmitis/microbiology , Eye Infections, Bacterial/microbiology , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Acute Disease , Aged , Anti-Bacterial Agents/pharmacology , Endophthalmitis/epidemiology , Endophthalmitis/physiopathology , Eye Infections, Bacterial/epidemiology , Eye Infections, Bacterial/physiopathology , Female , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , Taiwan/epidemiology , Visual Acuity
5.
Eye (Lond) ; 24(4): 547-52, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19648901

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of Ahmed glaucoma valve (AGV) implantation in Asian patients with refractory glaucoma. METHODS: The study was a retrospective interventional case series conducted at a single institution between January 2004 and January 2006. The study population included 91 patients (91 eyes). RESULTS: A total of 70 patients were successfully treated (74.5%). Postoperatively, the median intraocular pressures declined significantly to 13 mm Hg (interquartile range: 10-20 mm Hg) on day 1 (P<0.001) and 17 mm Hg (interquartile range: 12-19 mm Hg) at the last follow-up examination (P<0.001). The cumulative probability of success according to Kaplan-Meier life-table analysis was 74% at 12 months and 43% at 2 years. Hazard of failure increased slightly with age, HR: 1.03 (95% confidence interval (CI)=1.00-1.05; P=0.044). The most common complication was hyphaemia at 12.77%. There were no serious complications involving loss of visual acuity or sight. CONCLUSIONS: AGV implantation is an acceptable treatment for refractory glaucoma in high-risk patients with few additional options.


Subject(s)
Asian People , Glaucoma Drainage Implants , Glaucoma/surgery , Adult , Aged , Female , Glaucoma/ethnology , Glaucoma/physiopathology , Humans , Intraocular Pressure , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Visual Acuity
6.
Eye (Lond) ; 24(2): 354-60, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19478825

ABSTRACT

PURPOSE: To evaluate the effect of subretinal fluid (SRF) from rhegmatogenous retinal detachment (RRD) and blood on the expression of intercellular adhesion molecule-1 (ICAM-1) in the retinal pigment epithelium. METHODS: The study included 22 patients who had experienced RRD within 1 month before the study and 14 patients with macular holes or pucker. SRF was collected during surgery to repair RRD and the vitreous was collected during vitrectomy. The SRF was cocultured with ARPE-19 cells with and without glucosamine sulphate (GS) and triamcinolone acetonide (TA). Blood from peripheral veins and blood components (red blood cells, platelet-poor plasma, and platelet-rich plasma) were also cocultured with ARPE-19 cells. Vitreous samples were cocultured with ARPE-19 cells in the control. The expression of ICAM-1 was detected and quantified by using flow cytometry. RESULTS: The expression of ICAM-1 in RPE cells was significantly higher (P<0.05) after 24-h incubation of 40% SRF with ARPE-19 cells. In addition, the expression of ICAM-1 in retinal pigment epithelium (RPE) cells significantly increased (P<0.01) when cocultured with blood and blood components. However, there were no differences (P>0.05) in ICAM-1 expression when RPE cells were cocultured with or without GS or TA. CONCLUSIONS: SRF and blood enhanced the expression of ICAM-1 in RPE cells in this study and the increased expression of ICAM-1 by SRF is not inhibited by GS or TA.


Subject(s)
Coculture Techniques , Intercellular Adhesion Molecule-1/metabolism , Retinal Detachment/metabolism , Retinal Pigment Epithelium/metabolism , Cells, Cultured/metabolism , Exudates and Transudates/metabolism , Female , Humans , Male , Middle Aged , Retinal Detachment/blood , Retinal Detachment/surgery
7.
Osteoporos Int ; 21(1): 129-35, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19367351

ABSTRACT

UNLABELLED: We explored the relationship between extracts of oxyntic mucosa (EOM) and the biological activity of osteoblasts in rats. We found that EOM could enhance the activity of bone formation in osteoblast. Our results suggest that EOM likely play a role in the cases of osteopenia induced by gastrectomy. INTRODUCTION: Surgical removal of the stomach (gastrectomy) leads to osteopenia in animals and in humans. It was demonstrated that EOM could induce transient hypocalcaemia and stimulate an uptake of Ca(2+) into bone in rats. The main aim of this study has been to clarify whether this procedure was performed through osteoblast, which is responsible for bone formation. METHODS: Osteoblasts were isolated, cultured, and identified in vitro. Preparing the rats' EOM and diluting into low, middle, and high concentrations, respectively. After osteoblasts were treated by different concentration EOMs or saline (for control), the intracytoplasm [Ca(2+)]i was measured by laser scanning confocal microscopy; the proliferation of osteoblast cells were detected with cell counting kit 8 (CCK-8); and the expressions of collagen type I and osteocalcin were assayed by reverse transcriptase polymerase chain reaction and Western blot. RESULTS: EOMs were found to induce a dose-related rapid increase of intracytoplasm [Ca(2+)]i in osteoblasts and could stimulate osteoblasts to enhance proliferation and upregulate the expressions of collagen type I and osteocalcin significantly (p < 0.05) compared with the control group. CONCLUSIONS: It was confirmed that EOM could stimulate osteoblasts to elevate the cytoplasm [Ca(2+)]i and promote the multiplication and the activity of bone formation in osteoblasts.


Subject(s)
Cell Extracts/pharmacology , Osteoblasts/drug effects , Parietal Cells, Gastric/chemistry , Animals , Calcium/metabolism , Cell Extracts/administration & dosage , Cell Proliferation , Cells, Cultured , Collagen Type I/biosynthesis , Collagen Type I/genetics , Cytoplasm/metabolism , Male , Microscopy, Phase-Contrast/methods , Osteoblasts/cytology , Osteoblasts/metabolism , Osteocalcin/biosynthesis , Osteocalcin/genetics , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction/methods , Up-Regulation/drug effects
8.
J Biomol Struct Dyn ; 26(5): 549-59, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19236105

ABSTRACT

beta2-Microglobulin (beta2-m) forms amyloid fibrils in patients undergoing long-term hemodialysis. K3 peptide, a Ser20-Lys41 fragment of beta2-m, has been known to form fibrils over a wide range of pH and solvent conditions. Recent solid-state NMR has revealed that K3 oligomer adopts a parallel U-shaped beta-strand-turn-beta-strand motif. In order to investigate the stability and morphologies of K3 oligomers with different sizes (dimer, trimer, and tetramer) and organizations (single and double layers), several all-atom molecular dynamics simulations were conducted at 310 K and pH 2 in water and 2,2,2-trifluoroethanol (TFE). For single-layered organizations, our results show that TFE destabilizes the stacking of K3 peptides due to the fact that TFE weakens the intermolecular hydrophobic interactions of K3 oligomers. In addition, we also identified that the loop region is stabilized by the hydrophobic cluster involving resides Y7, F11, and I16. Our results further suggest that K3 tetramer is a potential minimal nucleus seed for the formation of K3 protofibrils. For double-layered organizations in water, our data demonstrate that K3 peptides can form various stable assemblies through different interfacial arrangements, such as NN, NC, and CC, by different driving forces. We further propose that the stacking of different interfaces between two facing beta-sheets of K3 peptides could be related to different fibril morphologies, which is in good agreement with the previous experimental results, showing that K3 protofibrils associated to formed mature fibrils with a wide range of diameters from 4 to 15 nm when they were transferred from 20% (v/v) TFE to aqueous solution.


Subject(s)
Amyloid/chemistry , Computer Simulation , Peptide Fragments/chemistry , beta 2-Microglobulin/chemistry , Dimerization , Humans , Hydrophobic and Hydrophilic Interactions , Models, Molecular
9.
Nanoscale Res Lett ; 4(12): 1452-7, 2009 Sep 18.
Article in English | MEDLINE | ID: mdl-20651925

ABSTRACT

In this article, SnO2nanowires (NWs) have been prepared and their microwave absorption properties have been investigated in detail. Complex permittivity and permeability of the SnO2NWs/paraffin composites have been measured in a frequency range of 0.1-18 GHz, and the measured results are compared with that calculated from effective medium theory. The value of maximum reflection loss for the composites with 20 vol.% SnO2NWs is approximately -32.5 dB at 14 GHz with a thickness of 5.0 mm.

10.
J Pathol ; 213(4): 412-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17973238

ABSTRACT

The purpose of this study was to define a biomarker panel for detection of cancer cells in cytologically negative sputum and to evaluate the panel for assessment of lung cancer risk. We examined 19 genetic and epigenetic markers using a sensitive fluorescence-based method in cytologically negative sputum and in lung tumour tissues from 82 lung cancer patients. We also used these markers to test the sputum of 37 cancer-free individuals who were matched by age, sex, and smoking habit. Based on the concordance of biomarkers in lung tumours and corresponding sputum, and the low prevalence in cancer-free individuals, we selected seven markers for a nested case-control study: microsatellite instability of D9S942; loss of heterozygosity of D9S286, D9S942, GATA49D12, and D13S170; and methylation of p16INK4a and RARbeta. Based on the assumption that a lung cancer cell has alterations in two or more of the seven biomarkers, we compared the pattern of biomarker alteration in lung tumours and corresponding sputum. Our comparison yielded a sensitivity of 82%, specificity of 75%, and concordance of 79%. Three cancer-free individuals were considered to have an elevated risk based on the criterion that their sputum showed alteration in two of the seven biomarkers. One individual was indeed diagnosed as having lung cancer 18 months after sputum collection. In the nested case-control study, six biomarkers showed significantly increased odds ratios ranging from 3.14 to 11.24. Our study defines a biomarker panel for detection of cancer cells in cytologically negative sputum and verifies its use for risk assessment of lung cancer. In combination with conventional diagnostic tools, this multiple genetic and epigenetic panel should improve the detection or risk assessment of lung cancer.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Genetic Markers , Lung Neoplasms/diagnosis , Sputum/cytology , Acid Anhydride Hydrolases/genetics , Base Sequence , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Case-Control Studies , DNA Methylation , Epigenesis, Genetic , Female , Genes, p16 , Humans , Loss of Heterozygosity , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Microsatellite Instability , Molecular Sequence Data , Neoplasm Proteins/genetics , Neoplasm Staging , Promoter Regions, Genetic/genetics , Receptors, Retinoic Acid/genetics , Risk Assessment/methods , Sensitivity and Specificity
11.
Folia Biol (Praha) ; 52(5): 156-60, 2006.
Article in English | MEDLINE | ID: mdl-17116287

ABSTRACT

The phosphorylation of histone H3 at Ser10, Ser28, Thr11 and Thr3 of the amino terminal has been proved related to mitosis of the mammalian cells. However, the function of the Thr3 phosphorylation of H3 remains unclear. In this study, indirect immunofluorescence labelling and laser confocal microscopy were used to examine the cellular dynamic distribution of Thr3-phosphorylated H3 at mitosis in CHO cells. The results showed that the Thr3 phosphorylation began at early prophase and spread throughout the chromosomes at late prophase. At metaphase, most of the Thr3-phosphorylated H3 was distributed along the entire chromosomal arms and maintained until early anaphase. During late anaphase and telophase, the fluorescent signal of Thr3-phosphorylated H3 disappeared from chromosomes. There was a precise spatial and temporal correlation between H3 phosphorylation of Thr3 and stages of chromatin condensation. The timing of Thr3 phosphorylation and dephosphorylation in mitosis were similar to that reported for Thr11 phosphorylation of H3. The Thr3-phosphorylated H3 localized along the arms of chromosomes during metaphase and early anaphase. It was different from the Ser10-phosphorylated H3, which localized at telomere regions, and Thr11-phosphorylated H3, which localized at centromeres. The results suggest that the Thr3 phosphorylation of histone H3 may play a specific role, which is different from Ser10 phosphorylation and Thr11 phosphorylation in mitosis.


Subject(s)
Histones/metabolism , Mitosis , Animals , CHO Cells , Cricetinae , Cricetulus , Fluorescent Antibody Technique , Microscopy, Confocal , Phosphorylation , Threonine/metabolism
12.
Eur J Ophthalmol ; 16(5): 663-6, 2006.
Article in English | MEDLINE | ID: mdl-17061215

ABSTRACT

PURPOSE: A prospective study was performed to evaluate refractive and ocular biometric changes in acute hyperglycemic status in patients with diabetes mellitus. METHODS: From January to August 2002, 48 eyes of 24 patients with persistent diabetes and a plasma glucose level>or=17 mmol/L or HbA1c>or=10.0% on admission were enrolled in this prospective study. Upon admission to Tri-Service General Hospital in Taipei, Taiwan, these patients underwent intensive glycemic control. The basic ophthalmic examinations, including visual acuity, intraocular pressure measurement, slit lamp, and fundus examinations, were conducted. The ocular parameters including refraction, anterior chamber depth, lens thickness, axial length, mean keratometry, and thinnest corneal thickness were evaluated by A-mode scan and Orbscan II. Each patient underwent clinical follow-up visits at 1, 2, and 4 weeks after the acute hyperglycemic episode. RESULTS: Of the 24 patients, 18 were male and 6 were female. The mean age of the patients was 55 years (range: 38 to 69). Comparing the refractive status on admission and at week 4, the authors found that 8 cases (16 eyes, 33%) showed hyperopia during hyperglycemia (+1.9+/-0.8 D), but in the other 16 cases (32 eyes, 67%), there were no significant changes. In addition, there were also no significant changes in anterior chamber depth, lens thickness, axial length, thinnest corneal thickness, or mean keratometry in the follow-up period. CONCLUSIONS: Transitory hyperglycemia produces hyperopia. The alteration in refractive index in the lens may contribute to the hyperopic change, but no change of ocular biometrics in lens or cornea is observed.


Subject(s)
Hyperglycemia/complications , Hyperopia/etiology , Refraction, Ocular/physiology , Acute Disease , Blood Glucose/metabolism , Cornea/diagnostic imaging , Disease Progression , Female , Follow-Up Studies , Humans , Hyperglycemia/blood , Hyperglycemia/physiopathology , Hyperopia/diagnostic imaging , Hyperopia/physiopathology , Male , Middle Aged , Prognosis , Prospective Studies , Ultrasonography
13.
AJNR Am J Neuroradiol ; 27(5): 1074-5, 2006 May.
Article in English | MEDLINE | ID: mdl-16687545

ABSTRACT

We describe a case of decerebrate rigidity, with preservation of consciousness, caused by a discrete pontine tegmentum lesion identified on MR imaging. Lesions within a certain brain stem region are responsible for decerebrate rigidity in animal studies, but there has been a lack of MR imaging evidence in humans. This report also implies that a discrete lesion was responsible for the decerebrate rigidity, while consciousness was preserved.


Subject(s)
Consciousness , Decerebrate State/diagnosis , Magnetic Resonance Imaging , Female , Humans , Middle Aged
14.
Br J Surg ; 92(3): 348-55, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15672423

ABSTRACT

BACKGROUND: Although liver resection is now a safe procedure, its role for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial. METHODS: This study compared the results of liver resection for HCC in patients with cirrhosis over two time intervals. One hundred and sixty-one patients had resection during period 1 (1991-1996) and 265 in period 2 (1997-2002). Early and long-term results after liver resection in the two periods were compared, and clinicopathological characteristics that influenced survival were identified. RESULTS: Tumour size was smaller, indocyanine green retention rate was higher, patients were older and a greater proportion of patients were asymptomatic in period 2 than period 1. Operative blood loss, need for blood transfusion, operative mortality rate, postoperative hospital stay and total hospital costs were significantly reduced in period 2. The 5-year disease-free survival rates were 28.2 and 33.9 per cent in periods 1 and 2 respectively (P = 0.042), and 5-year overall survival rates were 45.9 and 61.2 per cent (P < 0.001). Multivariate analysis identified serum alpha-fetoprotein level, need for blood transfusion and Union Internacional Contra la Cancrum tumour node metastasis stage as independent determinants of disease-free and overall survival. CONCLUSION: The results of liver resection for HCC in patients with cirrhosis improved over time. Liver resection remains a good treatment option in selected patients with HCC arising from a cirrhotic liver.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Cirrhosis/surgery , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Disease-Free Survival , Female , Humans , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Male , Middle Aged , Postoperative Care/methods , Preoperative Care/methods , Treatment Outcome
16.
J Endocrinol ; 176(3): 359-66, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12630921

ABSTRACT

The effects of a Japanese herbal medicine, Keishi-bukuryo-gan, and 17beta-estradiol on calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature were investigated in ovariectomized (OVX) rats. Ovariectomy not only potentiated CGRP-induced elevation of skin temperature and arterial vasorelaxation but also induced a lower concentration of endogenous CGRP in plasma and up-regulation of arterial CGRP receptors, suggesting that lowered CGRP in plasma due to ovarian hormone deficiency increases the number of CGRP receptors and consequently amplifies the stimulatory effects of CGRP to elevate skin temperature. Oral Keishi-bukuryo-gan (100-1000 mg/kg, once a day for 7 days) restored a series of CGRP-related responses observed in OVX rats by normalizing plasma CGRP levels in a dose-dependent manner as effectively as s.c. injection. 17Beta-estradiol (0.010 mg/kg, once a day for 7 days). However, Keishi-bukuryo-gan did not affect the lower concentration of plasma estradiol and the decreased uterine weight due to ovariectomy, although the hormone replacement of 17beta-estradiol restored them. These results suggest that Keishi-bukuryo-gan, which does not confer estrogen activity on plasma, may be useful for the treatment of hot flashes in patients for whom estrogen replacement therapy is contraindicated, as well as menopausal women.


Subject(s)
Calcitonin Gene-Related Peptide/pharmacology , Drugs, Chinese Herbal/pharmacology , Estradiol/pharmacology , Hot Flashes/therapy , Medicine, East Asian Traditional , Skin Temperature/drug effects , Administration, Oral , Animals , Calcitonin Gene-Related Peptide/blood , Dose-Response Relationship, Drug , Estradiol/blood , Female , Injections, Subcutaneous , Ovariectomy , Rats , Rats, Sprague-Dawley , Receptors, Calcitonin Gene-Related Peptide/metabolism
17.
J Endocrinol ; 175(1): 177-83, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12379501

ABSTRACT

We investigated the mechanism for the augmentation of the calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature in ovariectomized (OVX) rats. I.v. injection of alphaCGRP (10 micro g/kg) elevated skin temperature of the hind paws. The elevation was significantly greater in OVX rats than in sham-operated rats and was inhibited by pretreatment with human CGRP(8-37) (100-1000 micro g/kg i.v.), a CGRP receptor antagonist, in a dose-dependent manner. In addition, ovariectomy not only potentiated vasorelaxation due to alphaCGRP but increased the number of CGRP receptors in mesenteric arteries. Further, the plasma concentration of endogenous CGRP was significantly lower in OVX rats. These results suggest that the low concentration of plasma CGRP due to ovarian hormone deficiency may induce the increase in the number of CGRP receptors due to up-regulation. Therefore, the increased number of CGRP receptors may be responsible for potentiation of exogenous alphaCGRP-induced elevation of skin temperature in OVX rats. The mechanism underlying the hot flashes observed in menopausal women may also involve, in part, the up-regulation of CGRP receptors following ovarian hormone deficiency.


Subject(s)
Calcitonin Gene-Related Peptide/pharmacology , Hot Flashes/metabolism , Peptide Fragments/pharmacology , Receptors, Calcitonin Gene-Related Peptide/metabolism , Vasodilator Agents/pharmacology , Analysis of Variance , Animals , Calcitonin Gene-Related Peptide/blood , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide Receptor Antagonists , Dose-Response Relationship, Drug , Female , Hot Flashes/physiopathology , Humans , In Vitro Techniques , Mesenteric Arteries/metabolism , Mesenteric Arteries/physiopathology , Models, Animal , Ovariectomy , Protein Binding , Rats , Rats, Sprague-Dawley , Skin Temperature/drug effects , Vascular Resistance/drug effects
18.
Gene Ther ; 9(15): 1008-14, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12101431

ABSTRACT

Endogenous opioid peptides play an essential role in the intrinsic modulation and control of inflammatory pain, and could be therapeutically useful. These opioid peptides are synthesized as parts of larger precursor molecules. One such precursor molecule is pro-opiomelanocortin (POMC). In this study, we developed a gene-gun method for the transfer of POMC cDNA in vivo, and investigated its therapeutic effect on inflammatory pain in a rat model of formalin-induced pain. Human POMC cDNA was cloned into a modified pCMV plasmid and delivered to the skin of rats by gene gun. Three days after gene-gun injection, 1% formalin was injected. Endorphin levels were measured in the serum and skin after the formalin test, and skin histology was used to detect endorphin after green fluorescent protein (GFP; control) or POMC cDNA transfer. There was no significant difference in the results of acute nociceptive tests between the experimental and control groups. There was also no difference in response between the groups to phase 1 of the formalin test. However, rats which received POMC cDNA via gene-gun injection showed a significantly reduced response in phase 2 of the formalin test. Endorphin immunoreactivity in the skin increased approximately three- to four-fold in experimental animals compared with GFP-treated controls at day 3 after injection. The phase 2 response in animals treated with formalin and naloxone did not differ significantly from the control, implying that the analgesic effects of POMC cDNA particle injection in phase 2 of the formalin test are reversed by naloxone. There are two major findings from this study. First, in vivo DNA delivery by gene gun to the skin is feasible. Second, the production of beta-endorphin is insufficient to block phasic pain, but is effective against sensitization of the afferent neurons during phase 2 of the formalin test.


Subject(s)
Biolistics/methods , DNA, Complementary/administration & dosage , Genetic Therapy/methods , Pain Management , Pro-Opiomelanocortin/genetics , Adrenocorticotropic Hormone/blood , Animals , Endorphins/analysis , Endorphins/blood , Endorphins/metabolism , Formaldehyde , Humans , Male , Models, Animal , Rats , Rats, Sprague-Dawley , Skin/chemistry , Skin/metabolism , Transgenes
19.
Mol Urol ; 3(1): 33-39, 1999.
Article in English | MEDLINE | ID: mdl-10851294

ABSTRACT

Although the incidence and death rates for cancer of the prostate (CaP) in Taiwan have been among the lowest in the world, they have increased remarkably in recent years. Because of the very low autopsy rate in this country, prostate specimens obtained via cystoprostatectomy may provide a unique opportunity to study the incidence and status of latent cancer. From January 1992 to December 1997, 49 prostate specimens were obtained from patients with transitional-cell carcinoma of the urinary bladder (48 cases) or pelvic melanoma (one case). Patients' ages ranged from 47 to 89, with a mean age of 67.8 years. No patient had any clinical indication of CaP, as assessed by digital rectal examination. Each prostate was prepared with whole-mount transverse serial sections at 3-mm intervals from the apex to the bladder neck. The stained slides reviewed by two pathologists to evaluate the frequency and pathological status of acinar cancer lesions and high-grade prostatic intraepithelial neoplasia (PIN). Of the 49 patients evaluated, 16 (33%) had evidence of adenocarcinoma, and 24 (49%) had high-grade PIN. The incidence of unsuspected CaP in patients aged 40 to 59, 60 to 69, and >/=70 years was 25%, 32%, and 37%, respectively. The frequency of high-grade PIN in patients aged 40 to 59, 60 to 69, and >/=70 years was 25%, 42%, and 64%, respectively. The incidence of high-grade PIN in the 16 patients with unsuspected CaP was significantly higher than in the 31 patients without this early cancer (75% v 36%). Of the 16 patients with unsuspected cancer, 5 had multiple tumors (3 patients with two and 2 with multiple foci). The mean volume of the 24 tumors was 0.0786 cm(3), with a range of 0.008 to 0.393 cm(3), but only 6 tumors exceeded 0.1 cm(3) in volume (0.112, 0.112, 0.164, 0.245, 0.262, and 0.393 cm(3)). Eighty-eight percent of these early cancers were low grade (Gleason score 2-4). All unsuspected CaP were organ confined. The frequency of unsuspected CaP in Taiwanese men is relatively higher than in Chinese, as previous reported by Dr. Gu. However, the incidence of this latent cancer is comparable to that of U.S. men of the same age. These findings, together with the high incidence of high-grade PIN, suggest that the initial step in the induction of CaP in indigenous Taiwanese is similar to that in U.S. men. The lower number of reports of CaP in Taiwan might be attributable to: (1) lower volume of latent cancer in the Taiwanese compared with U.S. men; (2) underestimation of the incidence rate of CaP in Taiwan; or (3) different genetic or environmental status leading to a different progression rate.

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