ABSTRACT
Methamphetamine (MA) is a powerful and highly addictive psychostimulant. However, the neural substrate mediating MA-induced conditioned effects, an essential part of addiction, remain unclear. The present study investigated the involvement of the anterior cingulate cortex (ACC), the lateral nucleus of amygdala (LNA), and the mediodorsal nucleus of the thalamus (MD) in MA-conditioned place preference (CPP). Rats underwent bilateral radio-frequency lesions of the ACC, LNA, or MD followed by MA CPP training. Lesions of the MD, but not the ACC or LNA, disrupted MA CPP learning. To clarify the role of the MD on the different stages of the MA CPP memory process, bilateral microinfusions of lidocaine into the MD were performed 5 min prior to each conditioning trial, immediately after the conditioning trial, or 5 min before the testing phase. Pretesting, but not pre- or post-conditioning, infusions of lidocaine into the MD impaired MA CPP. Furthermore, a clear preference for the previously conditioned MA paired cues was expressed when the rats were tested again 24 h after infusions of lidocaine. These results are interpreted as indicating that the MD is specifically involved in the memory retrieval process of MA associated memory which suggests the MD could have an important role in relapse in individuals suffering from MA addiction.
Subject(s)
Choice Behavior/physiology , Conditioning, Psychological/physiology , Mediodorsal Thalamic Nucleus/physiology , Mental Recall/physiology , Methamphetamine/pharmacology , Amygdala/physiology , Animals , Choice Behavior/drug effects , Conditioning, Psychological/drug effects , Gyrus Cinguli/physiology , Lidocaine/administration & dosage , Lidocaine/pharmacology , Male , Mediodorsal Thalamic Nucleus/drug effects , Memory/drug effects , Memory/physiology , Mental Recall/drug effects , Microinjections , Rats , Rats, Sprague-DawleyABSTRACT
AIM: To evaluate the cytotoxicity of current root canal sealers to periodontal ligament (PDL) fibroblasts. METHODOLOGY: Five root canal sealers (Canals, Canals-N, Topseal, Sealapex, Tubliseal) were prepared and placed into transwells. After initial setting for 1 h, the transwells with sealers were placed into cultured PDL fibroblasts. They were cultured for further 3 or 18 h. Morphological changes were observed. Cell viability was estimated by 3-(4,5-dimethyl-thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay. RESULTS: Marked retraction and death of PDL fibroblasts were observed after exposure to Canals or Topseal for 3 h. A 3-h exposure of PDL fibroblasts to Tubliseal stimulated MTT reduction. Canals-N showed little cytotoxicity even after an exposure of 18 h. CONCLUSION: Canals was the most toxic sealer, followed by Topseal. Sealapex and Tubliseal had comparable and moderate cytotoxicity to PDL fibroblasts, whereas Canals-N showed little cytotoxicity. Exposure to Tubliseal may modulate MTT reduction in PDL fibroblasts. Canals-N had good biocompatibility.
Subject(s)
Periodontal Ligament/drug effects , Root Canal Filling Materials/toxicity , Analysis of Variance , Cell Survival/drug effects , Cells, Cultured , Fibroblasts/drug effects , Humans , Mitochondria/drug effects , Mitochondria/enzymology , Periodontal Ligament/cytology , Statistics, NonparametricABSTRACT
OBJECTIVE: To investigate serum levels of folate, B12, and total homocysteine (tHcy) in elderly post-stroke patients, and the possible correlations with radiological markers of neuropathology. DESIGN: Cross-sectional study. SETTING: Department of Neurology, Cardinal Tien Hospital. SUBJECTS: Eighty-nine elderly post-stroke patients were enrolled for dietary assessment and blood tests. Neuroradiological assessment was done in 62 of these patients. MAIN OUTCOME MEASURES: Dietary folate and vitamin B12 intakes were evaluated by a 24-h recall system using a semi-quantitative questionnaire. Circulating levels of folate, B12, and tHcy were measured. Magnetic resonance imaging (MRI) or computed tomography (CT) was used for evaluation of brain lesions including infarction and atrophy. RESULTS: Mean folate and B12 intakes of these post-stroke patients were 69% and 261% of the recommended dietary allowances (RDA), respectively. Inadequate folate levels, defined as serum folate < 6 ng/mL, was noted in 68% of these patients. Hyperhomocysteinemia levels (tHcy >or=15 micromol/L) were observed in 48%. According to tertiles of serum tHcy and folate levels, the rate of brain atrophy, but not brain infarctions, are significantly associated with elevated tHcy (P = 0.0126) and decreased folate levels (P = 0.0273). After adjustments for age, sex, disease status, brain infarctions and carotid stenosis, the odds ratio of brain atrophy was 9.8 (95% CI: 1.7-56.4, P = 0.0101) in the hyperhomocysteinemia group and 9.6 (95% CI: 1.1-81.3, P = 0.0377) in the low folate group (serum folate < 3.0 ng/mL) compared with the group with normal tHcy and folate levels. No significant association was noted between vitamin B12 levels and brain lesions. CONCLUSIONS: Our data shows that folate deficiency and hyperhomocysteinemia are prevalent in elderly post-stroke patients. These two conditions are strongly and independently associated with the development of brain atrophy.
Subject(s)
Brain/pathology , Folic Acid/blood , Homocysteine/blood , Stroke/blood , Vitamin B 12/blood , Vitamin B Complex/blood , Aged , Biomarkers/blood , Brain Infarction/blood , Brain Infarction/epidemiology , Brain Infarction/pathology , Cross-Sectional Studies , Female , Folic Acid/administration & dosage , Folic Acid Deficiency/blood , Folic Acid Deficiency/complications , Folic Acid Deficiency/epidemiology , Folic Acid Deficiency/pathology , Homocysteine/administration & dosage , Humans , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/epidemiology , Hyperhomocysteinemia/pathology , Magnetic Resonance Imaging , Male , Mental Recall , Nutrition Assessment , Nutrition Policy , Surveys and Questionnaires , Vitamin B 12/administration & dosage , Vitamin B Complex/administration & dosageABSTRACT
The aim of the study was to assess the adjunctive effects of orlistat on weight loss and the influence of weight reduction on glycaemic control in overweight Chinese female type 2 diabetic patients. A randomised, placebo-controlled, double-blind, 12-week study was conducted. Chinese female type 2 diabetic patients, overweight (body mass index > 25 kg/m(2)), poorly controlled glucose levels [glycosylated haemoglobin (HbA1c) > 8%], were randomly assigned to two groups. In addition to their oral hypoglycaemic agents (maximal doses of sulphonylureas and metformin), one group (n = 30) received a placebo and the other (n = 30) received orlistat 120 mg t.i.d. for 12 weeks. Comparing the changes that occurred after 12 weeks in the orlistat and placebo groups, the former showed significantly greater reduction in bodyweight (2.5 vs. 0.4 kg; p < 0.05), fasting plasma insulin level (p < 0.01), 2-h postprandial blood glucose after glucose challenge (p < 0.01), insulin resistance (p < 0.01), HbA1c (p < 0.05), total cholesterol and triglyceride levels (p < 0.05, respectively). No significant differences were found between treatment groups in blood pressure and heart rate. The addition of orlistat to oral hypoglycaemic agents resulted in a significant weight reduction and improvement of metabolic control in overweight Chinese female type 2 diabetic patients.
Subject(s)
Anti-Obesity Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Lactones/therapeutic use , Obesity/drug therapy , Body Mass Index , Caloric Restriction/methods , Double-Blind Method , Female , Humans , Obesity/diet therapy , Orlistat , Prospective Studies , Treatment OutcomeABSTRACT
AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.
Subject(s)
Blood Glucose/analysis , Diet, Vegetarian , Food Preferences/physiology , Insulin Resistance/physiology , Aged , Asian People , Blood Pressure , Body Mass Index , Buddhism , Dairy Products/analysis , Female , Glucose Tolerance Test , Homeostasis/physiology , Humans , Male , Meat Products/analysis , Middle Aged , Taiwan , Uric Acid/bloodABSTRACT
AIMS: To evaluate the relationship between surrogate measures of insulin sensitivity and results from euglycaemic insulin clamp in Chinese diabetic patients and their offspring. METHODS: The study included 59 volunteers from 20 diabetic families. Each participant completed a 75-g oral glucose tolerance test (OGTT) and a euglycaemic insulin clamp. We tested the correlation of surrogate measures of insulin sensitivity with M-values and M/I ratios (the amount of glucose infused during 90-120 min of the clamp was defined as M, and the mean values of plasma insulin during 90-120 min as I) from the euglycaemic insulin clamp. These measures included fasting insulin (FPI), insulin at 120 min of OGTT, insulin area under the curve of OGTT, fasting glucose-to-insulin ratio, homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and the Matsuda-DeFronzo index from OGTT. RESULTS: The Matsuda-DeFronzo index closely correlated to M-value and M/I in 21 diabetic, 38 non-diabetic individuals and the 59 participants overall (with M-value, r = 0.68, 0.84 and 0.84; with M/I, r = 0.71, 0.72 and 0.75, respectively, all P < 0.001). Without OGTT, HOMA %S was a good surrogate index for diabetic (correlated to M-value and M/I, r = 0.71 and 0.68, P = 0.001) and for non-diabetic subjects (to M-value, r = 0.73; to M/I, r = 0.55, both P < 0.001). FPI was as good as HOMA %S and Matsuda-DeFronzo index. CONCLUSIONS: The Matsuda-DeFronzo index, HOMA %S and FPI are good surrogate estimates of insulin sensitivity in Chinese diabetic subjects and their offspring.
Subject(s)
Diabetes Mellitus, Type 2/blood , Insulin/blood , Adult , Aged , Biomarkers/blood , China/ethnology , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/genetics , Fasting/blood , Female , Glucose Clamp Technique/methods , Glucose Clamp Technique/standards , Glucose Tolerance Test , Homeostasis , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Pedigree , Sensitivity and SpecificityABSTRACT
The purpose of the study was to identify a good abdominal obesity index for insulin resistance in offspring of diabetic patients. A total of 74 non-diabetic subjects (male =36; female =38) were recruited from a diabetic family study. The waist circumference (W), waist-hip ratio (WHR) and conicity index were used as the abdominal obesity indices. The body mass index (BMI) and indices obtained from bioelectric impedance analysis (BIA) (body fat percentage, fat mass and fat mass index) were used as overall obesity indices. Fasting plasma insulin (FPI), homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda-Defronzo index from oral glucose tolerance test were chosen as the insulin sensitivity indices. We correlated obesity indices with insulin resistance indices with age and family adjusted. W was closely correlated in both sexes of subjects with Matsuda-DeFronzo index (male, r=-0.661,p<0.001; female, r=-0.419,p=0.026), FPI (male, r=0.614,p=0.001; female, r=0.503,p=0.006) and HOMA-IR (male, r=0.609,p=0.001; female, r=0.472,p=0.011). WHR and its log transformation predicted insulin resistance only in males. BMI as an overall obesity index was in good correlation with Matsuda-DeFronzo index (male, r=-0.646,p<0.001; female, r=-0.469,p=0.012), FPI (male, r=0.711,p<0.001; female, r=0.464,p=0.013) and HOMA-IR (male, r=0.708,p<0.001; female, r=0.469,p=0.012). Overall obesity indices from BIA were similar to BMI to predict insulin resistance. In conclusion, W is a good abdominal obesity predictor of insulin resistance in offspring of diabetic patients in Taiwan.
Subject(s)
Adipose Tissue/anatomy & histology , Blood Glucose/metabolism , Body Constitution/physiology , Insulin Resistance , Obesity/physiopathology , Abdomen , Adult , Blood Glucose/analysis , Body Mass Index , Diabetes Mellitus, Type 2/genetics , Electric Impedance , Female , Glucose Tolerance Test , Humans , Insulin Resistance/genetics , Male , Obesity/complications , Predictive Value of Tests , Sex Factors , TaiwanABSTRACT
The purpose of the study is to examine the differences in insulin resistance and postprandial triglyceride (TG) response between hypertensive patients with or without hypertriglyceridaemia. The study is a comparative cohort study with matching. Thirty-one newly diagnosed hypertensive patients without any medication were recruited from a health survey. The participants were further divided into two groups: those with fasting TG <2.26 mmol/L, and those with TG between 2.26 and 5.65 mmol/L. Both groups were matched in age, sex, body mass index and waist circumference. Each patient received a 75-g oral glucose tolerance test, an insulin suppression test, and a 1000 kcal high fat mixed meal test. The hypertriglyceridaemic hypertensive patients had significantly higher fasting insulin, 2-h plasma glucose, 2-h insulin, and steady-state plasma glucose (SSPG) (13.16 +/- 1.87 vs 9.76 +/- 3.18 mmol/L). They also had a greater postprandial TG response to the challenge of mixed meal (DeltaAUC 20.76 +/- 10.06 vs 7.97 +/- 3.18 mmol 8 h/L). The postprandial TG response was closely correlated (r = 0.72-0.95, P < 0.0001) with fasting TG in all hypertensive patients. Both fasting TG levels and postprandial TG response were significantly (P < 0.05) correlated with SSPG. In conclusion, the hypertensive patients with hypertriglyceridaemia were more insulin resistant than those without it. Exacerbation of postprandial hypertriglyceridaemia was identified in these patients. The TG response to the challenge of high fat meal was significantly correlated with fasting TG and insulin resistant in them. The results provide a rationale for the alleviation of insulin resistance and hypertriglyceridaemia in these atherosclerosis-prone hypertensive patients.
Subject(s)
Hypertension/blood , Hypertension/physiopathology , Hypertriglyceridemia/blood , Hypertriglyceridemia/physiopathology , Insulin Resistance/physiology , Postprandial Period/physiology , Triglycerides/blood , Adult , Aged , Body Composition , Cohort Studies , Female , Humans , Hypertension/complications , Hypertriglyceridemia/complications , Male , Middle Aged , Severity of Illness IndexABSTRACT
Propylthiouracil (PTU)-induced hemolytic anemia is extremely rare. We reported a case of Graves' disease with these unusual clinical manifestations. A 41-year-old female presented with recurrent attacks of severe hemolytic anemia after PTU therapy. Sugar water test and erythrocytes osmotic fragility test revealed no cellular membrane defect of red blood cells. Antinuclear antibody, direct and indirect Coombs' tests were all negative and glucose-6-phosphate dehydrogenase activity was also within normal limits. PTU was not discontinued promptly due to unrecognizableness of such a rare case until two months later with recurrent attacks of severe hemolytic anemia. 1-131 therapy was performed on suspicion of related hemolytic anemia. Unfortunately, challenge of PTU occurred incidentally after discontinuation of PTU followed by severe hemolytic anemia. The diagnosis of PTU-induced hemolytic anemia was established thereafter. A MEDLINE search revealed only one such case reported in English literature. This is the first case report in Taiwan. It should be kept in mind that hemolytic anemia may be a rare complication of PTU therapy.
Subject(s)
Anemia, Hemolytic/chemically induced , Antithyroid Agents/adverse effects , Propylthiouracil/adverse effects , Adult , Female , Graves Disease/drug therapy , HumansABSTRACT
A total of 89 isolates of Streptococcus pneumoniae were obtained from 86 patients during the period from November 1996 through September 1999 at the Kaohsiung Medical University Hospital. The purpose of this study was to determine the antimicrobial susceptibilities and the distribution of serotypes of these isolates, and to correlate these findings with the clinical characteristics of patients. Twenty-one (23.6%) isolates were obtained from patients aged below 5 years, and 38 (42.7%) from patients aged over 65 years. These 86 patients included 53 pneumonia, 13 bacteremia (including 6 with septic shock), 8 urinary tract infection, 8 soft tissue infections, 7 acute exacerbation of chronic bronchitis, 2 ophthalmic infection, and 2 cholecystitis cases. The most frequent serotypes were types 20 (10.1%), 6 (9%), 10 (9%), 11 (9%), and 23 (9%). All isolates were included in the serotypes represented in the 23-valent pneumococcal vaccine. Thirty-four (38.2%) isolates showed reduced penicillin susceptibility by the E-test. The predominant serotypes of penicillin-resistant S. pneumoniae were types 11 (17.6%), 7 (14.7%), 6 (8.8%), 8 (8.8%), and 23 (8.8%). All isolates were susceptible to vancomycin. Resistance rate to erythromycin was 49.4%, chloramphenicol, 20.2%; and trimethoprim/sulfamethoxazole, 61.8%. Multiple resistance (> or = 3 classes of antibiotics) was found in 28 (31.5%) isolates, of which the majority were serotypes 11 (14.3%), 7 (14.3%), 6 (10.7%), 8 (10.7%), and 23 (10.7%).
Subject(s)
Drug Resistance, Multiple, Bacterial , Pneumococcal Infections/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Pneumococcal Infections/drug therapy , Seroepidemiologic Studies , TaiwanABSTRACT
To determine whether a semi-automatic oscillometric blood pressure (BP) monitor Dinamap 1846SX (DIN) can replace the standard mercury sphygmomanometer (SMS) for BP measurements in diabetic patients and their offspring, we compared SMS with DIN in 105 diabetic patients and their families. Their mean age was 50.6 (range 24-86) years, of whom 41 had diabetes mellitus (DM), 32 impaired glucose tolerance and 32 non-DM. After resting quietly for 10 min, their right arm BP were measured twice with each device at random and with 1-min intervals between each measurement. Agreement between measurements was tested by plotting the differences between the methods against means and by intraclass correlation coefficient (r(I)). The DIN was also evaluated by the criteria of American Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society (BHS) criteria and clinical criteria of O'Brien. All measurements by DIN [first readings or averaged readings of duplicate measurements of systolic BP (SBP) or diastolic BP (DBP)] satisfied the AAMI criteria and had good agreement with SMS (r(I)=. 951 for SBP and r(I)=.905 for DBP). The first readings of systolic BP measured by DIN vs. SMS failed to satisfy the criteria by O'Brien and reached BHS grade C level. Other measurements passed the limits of O'Brien and reached BHS grade A or B. In conclusion, averaged readings of duplicate BP measurements by DIN are interchangeable with that by SMS in Chinese diabetic patients and their offspring. Only one single DIN measurement is not acceptable for clinical application.
Subject(s)
Blood Pressure Determination/methods , Blood Pressure Monitors , Blood Pressure/physiology , Diabetes Mellitus/genetics , Diabetes Mellitus/physiopathology , Sphygmomanometers , Adult , Aged , Aged, 80 and over , Automation , Diastole , Female , Glucose Intolerance/genetics , Glucose Intolerance/physiopathology , Humans , Male , Middle Aged , Nuclear Family , Oscillometry , Regression Analysis , SystoleABSTRACT
Representation difference analysis (RDA) was applied to isolate a Mycoplasma arthritidis specific DNA fragment. The DNA fragment obtained was verified to be M. arthritidis specific by polymerase chain reaction (PCR) and dot blot hybridization tests. The size of this fragment was 194 bp and the nucleotide sequence was also determined.
Subject(s)
DNA, Bacterial/analysis , Mycoplasma/genetics , Base Sequence , Cloning, Molecular , DNA, Bacterial/chemistry , Molecular Sequence Data , Nucleic Acid Hybridization , Polymerase Chain Reaction , Sensitivity and SpecificityABSTRACT
The TRK protooncogene (NTRK1) encodes a cell-surface transmembrane tyrosine kinase (TK) acting as a receptor for nerve growth factor. Oncogenic potential in thyrocytes results from replacing the 5' portion by regulatory parts of other genes, leading to constitutive TK expression. In Italy, human papillary thyroid carcinoma (PTC) shows a frequent activation (50%) of the TK receptor genes NTRK1 and RET. Both genes undergo oncogenic rearrangements by the same mechanism. We previously reported high frequency (6/11) of rearrangement of the RET protooncogene in Chinese PTCs. Wide differences in the frequency (0-10.9%) of the NTRK1 rearrangement in PTCs have been reported in different populations. To investigate the frequency of TRK protooncogene rearrangement in Chinese thyroid tumors, we performed reverse transcriptase polymerase chain reaction to amplify specific TRK rearrangement transcripts. We examined thyroid tumors of 40 patients, including 14 papillary carcinomas, 4 follicular carcinomas, 1 Hurthle cell carcinoma, 1 insular carcinoma, and 20 nodular goiters. NF874 NIH3T3, NF723 NIH3T3, NF861 NIH3T3, and NF881 NIH3T3 were used as controls for TRK-T3, TRK-T2, TRK-T1, and TRK, respectively. No known TRK protooncogene rearrangements were detected among the 40 thyroid tumors in our studies. We suggest that the TK receptor NTRK1 activation seems less important than RET activation in PTCs in the Chinese population.
Subject(s)
Drosophila Proteins , Gene Rearrangement , Receptor, trkA/genetics , Thyroid Neoplasms/genetics , Adenocarcinoma/genetics , Adenocarcinoma, Follicular/genetics , Carcinoma, Papillary/genetics , Goiter, Nodular/genetics , Humans , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-ret , RNA, Messenger/analysis , Receptor Protein-Tyrosine Kinases/genetics , Reverse Transcriptase Polymerase Chain Reaction , TaiwanABSTRACT
ER-to-Golgi transport, and perhaps intraGolgi transport involves a set of interacting soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins including syntaxin 5, GOS-28, membrin, rsec22b, and rbet1. By immunoelectron microscopy we find that rsec22b and rbet1 are enriched in COPII-coated vesicles that bud from the ER and presumably fuse with nearby vesicular tubular clusters (VTCs). However, all of the SNAREs were found on both COPII- and COPI-coated membranes, indicating that similar SNARE machinery directs both vesicle pathways. rsec22b and rbet1 do not appear beyond the first Golgi cisterna, whereas syntaxin 5 and membrin penetrate deeply into the Golgi stacks. Temperature shifts reveal that membrin, rsec22b, rbet1, and syntaxin 5 are present together on membranes that rapidly recycle between peripheral and Golgi-centric locations. GOS-28, on the other hand, maintains a fixed localization in the Golgi. By immunoprecipitation analysis, syntaxin 5 exists in at least two major subcomplexes: one containing syntaxin 5 (34-kD isoform) and GOS-28, and another containing syntaxin 5 (41- and 34-kD isoforms), membrin, rsec22b, and rbet1. Both subcomplexes appear to involve direct interactions of each SNARE with syntaxin 5. Our results indicate a central role for complexes among rbet1, rsec22b, membrin, and syntaxin 5 (34 and 41 kD) at two membrane fusion interfaces: the fusion of ER-derived vesicles with VTCs, and the assembly of VTCs to form cis-Golgi elements. The 34-kD syntaxin 5 isoform, membrin, and GOS-28 may function in intraGolgi transport.
Subject(s)
Endoplasmic Reticulum/metabolism , Golgi Apparatus/metabolism , Membrane Proteins/physiology , Vesicular Transport Proteins , Animals , COS Cells , Humans , Membrane Proteins/metabolism , Mice , PC12 Cells , Precipitin Tests , Qa-SNARE Proteins , Qb-SNARE Proteins , Qc-SNARE Proteins , R-SNARE Proteins , Rabbits , Rats , SNARE Proteins , Subcellular Fractions , Temperature , Tumor Cells, CulturedABSTRACT
Genomic clones for Cyp4a12 and a novel member of the murine Cyp4a gene family were isolated. The novel gene, designated Cyp4a14, has a GC rich sequence immediately 5' of the transcription start site, and is similar to the rat CYP4A2 and CYP4A3 genes. The Cyp4a14 gene spans approximately 13 kb, and contains 12 exons; sequence similarity to the rat CYP4A2 gene sequence falls off 300 bp upstream from the start site. In view of the known sex-specific expression of the rat CYP4A2 gene, the expression and inducibility of Cyp4a14 was examined. The gene was highly inducible in the liver when mice were treated with the peroxisome proliferator, methylclofenapate; induction levels were low in control animals and no sex differences in expression were observed. By contrast, the Cyp4a12 RNA was highly expressed in liver and kidney of control male mice but was expressed at very low levels in liver and kidney of female mice. Testosterone treatment increased the level of this RNA in female liver slightly, and to a greater extent in the kidney of female mice. In agreement with studies on the cognate RNA, expression of Cyp4a12 protein was male-specific in the liver of control mice and extremely high inducibility of Cyp4a10 protein, with no sex differences, was also demonstrated. In view of the overlapping patterns of inducibility of the three Cyp4a genes, we investigated whether the three genes were co-localized in the genome. Two overlapping yeast artificial chromosome (YAC) clones were isolated, and the three Cyp4a genes were shown to be present on a single YAC of 220 kb. The Cyp4a genes are adjacent to the Cyp4b1 gene, with Cyp4a12 most distant from Cyp4b1. The clustering of these two gene subfamilies in the mouse was replicated in the human, where the CYPA411 and CYP4B1 genes were present in a single YAC clone of 440 kb. However, the human CYP4F2 gene was mapped to chromosome 19. Phylogenetic analysis of the CYP4 gene families demonstrated that CYP4A and CYP4B are more closely related than CYP4F.
Subject(s)
Cytochrome P-450 Enzyme System/genetics , Mixed Function Oxygenases/genetics , Multigene Family , Amino Acid Sequence , Animals , Base Sequence , Chromosomes, Artificial, Yeast , Cloning, Molecular , Cytochrome P-450 CYP4A , DNA, Complementary , Female , Gene Expression Regulation, Enzymologic , Genetic Linkage , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Molecular Sequence Data , Rats , Sequence Homology, Amino AcidABSTRACT
The proposed cis-Golgi vesicle receptor syntaxin 5 was found in a complex with Golgi-associated SNARE of 28 kDa (GOS-28), rbet1, rsly1, and two novel proteins characterized herein: rat sec22b and membrin, both cytoplasmically oriented integral membrane proteins. The complex appears to recapitulate vesicle docking interactions of proteins originating from distinct compartments, since syntaxin 5, rbet1, and GOS-28 localize to Golgi membranes, whereas mouse sec22b and membrin accumulate in the endoplasmic reticulum. Protein interactions in the complex are dramatically rearranged by N-ethylmaleimide-sensitive factor. The complex consists of two or more subcomplexes with some members (rat sec22b and syntaxin 5) in common and others (rbet1 and GOS-28) mutually exclusively associated. We propose that these protein interactions determine vesicle docking/fusion fidelity between the endoplasmic reticulum and Golgi.
Subject(s)
Endoplasmic Reticulum/metabolism , Golgi Apparatus/metabolism , Membrane Proteins/genetics , Synaptic Vesicles/metabolism , Vesicular Transport Proteins , Animals , Biological Transport/physiology , COS Cells/physiology , Carrier Proteins/physiology , Detergents , Endoplasmic Reticulum/chemistry , Epitopes/analysis , Gene Expression/physiology , Golgi Apparatus/chemistry , Mammals , Membrane Proteins/analysis , Membrane Proteins/isolation & purification , Membrane Proteins/physiology , Mice , Molecular Sequence Data , N-Ethylmaleimide-Sensitive Proteins , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/isolation & purification , Neurons/cytology , Neurons/metabolism , Qa-SNARE Proteins , Qb-SNARE Proteins , Qc-SNARE Proteins , R-SNARE Proteins , Rabbits , Rats , Rats, Sprague-Dawley , Sequence Homology, Amino Acid , Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins , Subcellular Fractions/chemistry , Synaptic Vesicles/chemistryABSTRACT
Intraperitoneal migration of an abdominally implanted cardioverter defibrillator is a complication not yet fully described. In a consecutive series of 195 patients, migration occurred between 1 and 20 months in 5 (8%) of the 63 patients in whom a subrectus abdomini placement of the generator was chosen. It was unrelated to the patients' clinical characteristics or the defibrillator model. Dysuria and inability to interrogate the device were present in every subject, and the diagnosis was confirmed by the characteristic abdominal x-ray appearance and the findings at the time of surgery. Adhesions involving the omentum, and in one case, the small bowels, were present in three patients and seem to be related to the length of intraabdominal permanence of the generator. Because this complication may be due to specific anatomical characteristics of the aponeurosis of the abdominal muscles, it is likely that its incidence will be unchanged by the use of smaller devices. A close follow-up of the generators implanted deep to the rectus fascia is therefore advisable.
Subject(s)
Defibrillators, Implantable , Foreign-Body Migration , Abdomen , Abdominal Muscles , Adult , Aged , Female , Humans , MaleABSTRACT
Primary malignant cardiac tumors are uncommon, and cardiac leiomyosarcoma is extremely rare. We reported a case of left atrial (LA) leiomyosarcoma with unusual clinical manifestations. A 28-year-old female presented with unknown cause of fever, body weight loss and anemia for two months. Echocardiography and magnetic resonance image study disclosed a 5 x 3 x 3.6 cm3 lobulated mass in the LA with invasion to its posterior wall. Histologic and immuno-histochemical studies of the resected specimen revealed a picture of leiomyosarcoma. The patient improved after surgical resection and post-operative chemotherapy. The literature was reviewed with a discussion of the clinical manifestations, diagnosis and treatment strategy of this rare tumor. Diagnosis of LA leiomyosarcoma is frequently delayed to make a very poor prognosis. Postoperative chemotherapy should be considered because of highly possible incomplete resection. However, an optimal treatment regimen remains unknown.
Subject(s)
Heart Neoplasms/surgery , Leiomyosarcoma/surgery , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Dacarbazine/administration & dosage , Doxorubicin/administration & dosage , Female , Fever of Unknown Origin/etiology , Heart Atria , Heart Neoplasms/drug therapy , Humans , Leiomyosarcoma/drug therapyABSTRACT
PURPOSE: The aim of this project was to evaluate the feasibility of aortoscopy for guidance of endoluminal aortic procedures and to determine whether aortoscopy has advantages over fluoroscopy in a pig model. METHODS: To establish feasibility aortoscopic guidance was used for making endoluminal aortic measurements, cannulating small arteries for arteriograpy, and placing intraaortic stents and grafts in 11 pigs. To compare aortoscopy and fluoroscopy measurements were made and stents were placed by a surgeon using only aortoscopic guidance in 10 pigs and by an interventional radiologist using only fluoroscopic guidance in 10 pigs. Postmortem dissections were performed to determine measurement and device placement accuracy. RESULTS: In the feasibility study aortoscopic measurements differed from postmortem measurements by a mean distance (+/- SD) of 1.2 +/- 0.2 mm. Stents and grafts were placed a mean of 2.3 +/- 1.9 mm distal to the most inferior renal artery with no stent covering an orifice. All attempts at cannulating spinal arteries greater than 2 mm in diameter were successful. In the comparison of aortoscopic and fluoroscopic guidance, fluoroscopic measurements differed from postmortem measurements by 2.6 +/- 2.4 mm (p = 0.223). Stents placed with aortoscopic guidance were 1.1 +/- 1.3 mm distal to the most inferior renal artery, whereas stents placed with fluoroscopic guidance were 3.4 +/- 2.5 mm distal to the most inferior renal artery (p = 0.019). CONCLUSIONS: These results demonstrate that aortoscopy is a useful guidance system for endoluminal aortic procedures and may have advantages over fluoroscopy alone.
Subject(s)
Angioscopes , Aorta/surgery , Endoscopes , Animals , Aortography , Equipment Design , Feasibility Studies , Fluoroscopy , Radiography, Interventional , Stents , SwineABSTRACT
PURPOSE: Balloon aortoscopy has been described for viewing aortic endoluminal anatomy and guiding aortic stent placement in animals. We report the first clinical use of this technique to visually inspect the proximal portion of a 1-year-old endovascular aortic graft, its proximal fixation stent, and its relationship to the renal arteries. METHODS: The aortoscope is a modified fiber-optic endoscope that is fitted over the lens with a transparent, saline-filled balloon for blood displacement. Its performance was evaluated in a 62-year-old woman who had a Parodi-type Dacron/modified Palmaz stent endoluminal graft implanted to exclude an infrarenal aortic aneurysm in 1994. One year later, during an angioplasty procedure for symptomatic left subclavian and left common iliac artery stenoses, the 1-year-old endoluminal graft was inspected with the balloon-tipped angioscopic assembly. RESULTS: Introduced via the left brachial artery, the aortoscope provided a panoramic view of the endoluminal surface through the solution-filled balloon. The endoluminal aortic graft was clearly identified, as were both renal artery orifices proximal to the graft. The surface of the proximal stent was smooth and without exposed metal. No complications occurred with the angioscopy technique. CONCLUSIONS: Aortic angioscopy can be used to evaluate endoluminal aortic grafts and endoluminal anatomy. It provides clear, magnified views that may be useful for guiding precise placement and assessing the function and healing of endoluminal devices in the aorta.