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1.
BMC Geriatr ; 22(1): 205, 2022 03 14.
Article in English | MEDLINE | ID: mdl-35287578

ABSTRACT

BACKGROUND: The high prevalence of falling among older adults constitutes a major public and clinical health concern. Many elderly persons may develop activities-specific restriction due to the risk of falling. This highlights the need for relevant evaluative tools. METHODS: This cross-sectional study used activities-specific performance frequency indicators to quantify activity restrictions in elderly participants, with all measures based on items from the Activities-Specific Balance Confidence (ABC) scale. Specifically, we tested for correlations between activities-specific performance frequency and balance confidence, functional balance/mobility, and fall history. There were 88 elderly participants, including 28 with stroke, 30 with Parkinson's disease, and 30 with no neurological diseases. In addition to their activities-specific performance frequency measures, we collected a series of demographic and health-related characteristics from each participant. We analyzed between-group differences in activities-specific performance frequency and other demographic and health-related characteristics via the one-way analysis of variance and Kruskal-Wallis test. Next, we used the Spearman's rank correlation test and binary logistic regression to investigate the correlations between activities-specific performance frequency and demographic/other health-related characteristics. RESULTS: There were significant group differences in performance frequency for all ABC activity items except for walking around the house, average ABC scores, and functional balance/mobility among normal older adults, participants with strokes and those with Parkinson's disease. Activities-specific performance frequency showed stronger correlations with activities-relevant functional mobility (r=0.250-0.713 for 15 items with significant correlations, 13 activity items with r≧0.4) than with balance confidence (r=0.279-0.668 for 13 items with significant correlations, 10 activity items with r≧0.4). The performance frequency of walking in crowds/bumped was the most sensitive measure for predicting fallers (odd ratio=3.310, p<0.05). CONCLUSIONS: This study proposed and validated the usage of activities-specific performance frequency as an alternative method for quantifying activity restrictions among older adults.


Subject(s)
Parkinson Disease , Aged , Cross-Sectional Studies , Geriatric Assessment/methods , Humans , Postural Balance
2.
Opt Express ; 29(21): 33836-33849, 2021 Oct 11.
Article in English | MEDLINE | ID: mdl-34809187

ABSTRACT

We present a theoretical overview and experimental demonstration of a continuous-wave, cavity-enhanced optical absorption spectrometry method to detect molecular gas. This technique utilizes the two non-degenerate polarization modes of a birefringent cavity to obtain a zero background readout of the intra-cavity absorption. We use a double-pass equilateral triangle optical cavity design with additional feed-forward frequency noise correction to measure the R14e absorption line in the 30012←00001 band of CO2 at 1572.655 nm. We demonstrate a shot noise equivalent absorption of 3 × 10-13 cm-1 Hz-1/2.

3.
Microbiologyopen ; 9(11): e1119, 2020 11.
Article in English | MEDLINE | ID: mdl-33034165

ABSTRACT

The gut microbiota plays multiple critical roles in maintaining the health of the host, especially in ruminants. However, our understanding of the establishment of gut microbiota from birth to adulthood is still limited. To address this, the bacterial ecology of the rumen, abomasum, duodenum, and rectum in Holstein cows ranging in age from 1 week to 5 years old was investigated using 16S rRNA gene sequencing in this study. A major change in the composition, diversity, and abundance of bacteria was observed with increased age (p < 0.05). Microbiota gradually matured in each gut segment and followed the Gompertz model when the Chao1, Shannon, and maturity indexes (p < 0.05, r > 0.94) were applied. Importantly, the Gompertz model parameter differed between the gut segments, with the highest microbiota growth rate found in the rectum, followed by the rumen, abomasum, and duodenum. Compared to older animals, greater microbiota similarities were found in the adjacent gut segments of younger animals (p < 0.05). Our findings indicate that gut microbiotas are established quickly when cows are young and then slow with age and that early in life, hindgut microbiota may be more easily affected by the foregut microbiota.


Subject(s)
Bacteria/classification , Bacteria/isolation & purification , Bacterial Load , Gastrointestinal Microbiome/physiology , Abomasum/microbiology , Animals , Bacteria/genetics , Bacteria/growth & development , Cattle , Duodenum/microbiology , Gastrointestinal Microbiome/genetics , RNA, Ribosomal, 16S/genetics , Rectum/microbiology , Rumen/microbiology
5.
Clin Lab ; 65(7)2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31307164

ABSTRACT

BACKGROUND: We report an acute pulmonary embolism with negative D-dimer masquerading as right pneumonia with pleural effusion proven by CT pulmonary arteriography (CTPA). METHODS: Appropriate laboratory tests are carried out. The application of vascular ultrasound for the cause of left lower extremity edema. CTPA were performed when vascular ultrasound suggested the existence of venous thrombosis of left lower extremity. RESULTS: Serum D-dimer was negative. Vascular ultrasound revealed left lower extremity venous thrombosis, CTPA demonstrated large emboli in the main pulmonary artery and main pulmonary artery branches. CONCLUSIONS: Negative serum D-dimer is not safe to rule out acute pulmonary embolism. When CT shows peripheral triangle-shaped infiltrate with pleuritis or small pleural exudate, physicians should pay attention to pulmonary infarction.


Subject(s)
Angiography/methods , Fibrin Fibrinogen Degradation Products/analysis , Pleural Effusion/diagnostic imaging , Pneumonia/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Tomography, X-Ray Computed/methods , Acute Disease , Diagnosis, Differential , Humans , Male , Middle Aged , Pleural Effusion/complications , Pneumonia/complications , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/etiology , Reproducibility of Results , Sensitivity and Specificity
6.
Front Microbiol ; 8: 1208, 2017.
Article in English | MEDLINE | ID: mdl-28702022

ABSTRACT

Gut microbiota plays multiple important roles in intestinal and physiological homeostasis, and using fecal microbiota transplantation (FMT) to reprogram gut microbiota has demonstrated promise for redressing intestinal and physiological disorders. This study tested the alterations in reprogramming efficiency caused by different gut preparation procedures and explored the associated underlying mechanisms. We prepared the guts of mice for FMT by administering one of the three most-clinically used pretreatments [antibiotics, bowel cleansing (BC) solution, or no pretreatment], and we found that preparing the gut with antibiotics induced a more efficient modification of the gut bacterial community than was induced by either of the other two pretreatment types. The increased efficiency of antibiotic treatment appeared to occur via increasing the xenomicrobiota colonization. Further analysis demonstrated that antibiotic treatment of mice induced intestinal microbiota disruption, mostly by expelling antibiotic-sensitive bacteria, while the indigenous microbiota was maintained after treatment with a BC solution or in the absence of pretreatment. The amount of antibiotic-resistant bacteria increased shortly after antibiotics usage but subsequently decreased after FMT administration. Together, these results suggest that FMT relied on the available niches in the intestinal mucosa and that preparing the gut with antibiotics facilitated xenomicrobiota colonization in the intestinal mucosa, which thus enhanced the overall gut microbiota reprogramming efficiency.

7.
Kidney Int ; 89(2): 439-49, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26466319

ABSTRACT

p-Cresyl sulfate (PCS) is a risk factor of cardiovascular disease in patients with chronic kidney disease. Here we tested whether serum PCS levels were related to the rate and evolution of carotid atherosclerosis in hemodialysis patients and identified a potential mechanism. A total of 200 hemodialysis patients were categorized as with or without carotid atherosclerotic plaque and followed for 5 years. Serum PCS levels were found to be higher in patients with than without carotid atherosclerotic plaque and positively correlated with increased total plaque area during follow-up. Multiple logistic regression and mixed effects model analyses showed that serum PCS levels were independently associated with the incidence and progression of carotid atherosclerotic plaque. PCS induced inflammatory factor and adhesion molecule expression in endothelial cells and macrophages. In addition, PCS triggered monocyte-endothelial cell interaction in vitro and in vivo through increased production of reactive oxygen species. Compared with controls, increase of PCS levels produced by gavage promoted atherogenesis in 5/6-nephrectomized apoE-/- mice; a process attenuated by NADPH oxidase inhibitors. Thus, increased serum PCS levels are associated with the occurrence and progression of carotid atherosclerosis in hemodialysis patients and promote atherogenesis through increased reactive oxygen species production.


Subject(s)
Carotid Artery Diseases/blood , Cresols/blood , Kidney Failure, Chronic/complications , Sulfuric Acid Esters/blood , Acetophenones , Adult , Aged , Animals , Aorta/metabolism , Apolipoproteins E/deficiency , Carotid Artery Diseases/etiology , Case-Control Studies , Disease Progression , Endothelial Cells/physiology , Female , Humans , Kidney Failure, Chronic/blood , Macrophages/physiology , Male , Mice , Middle Aged , NADPH Oxidases/metabolism , Reactive Oxygen Species/metabolism
9.
Chemphyschem ; 15(10): 1956-69, 2014 Jul 21.
Article in English | MEDLINE | ID: mdl-25044525

ABSTRACT

Developing a stable and safe electrolyte that works at voltages as high as 5 V is a formidable challenge in present Li-ion-battery research because such high voltages are beyond the electrochemical stability of the conventional carbonate-based solvents available. In the past few years, extensive efforts have been carried out by the research community toward the exploration of high-voltage electrolytes. In this review, recent progress in the study of several promising high-voltage electrolyte systems, as well as their recipes, electrochemical performance, electrode compatibility, and characterization methods, are summarized and reviewed. These new electrolyte systems include high-voltage film-forming additives and new solvents, such as sulfones, ionic liquids, nitriles, and fluorinated carbonates. It appears to be very difficult to find a good high-voltage (∼5 V) electrolyte with a single-component solvent at the present stage. Using mixed fluorinated-carbonate solvents and additives are two realistic solutions for practical applications in the near term, while sulfones, nitriles, ionic liquids and solid-state electrolyte/polymer electrolytes are promising candidates for the next generation of high-voltage electrolyte systems.

10.
J Phys Chem B ; 117(40): 12319-27, 2013 Oct 10.
Article in English | MEDLINE | ID: mdl-24041255

ABSTRACT

The sedimentation of a charged porous sphere at the center of a charged spherical cavity filled with an electrolyte solution is analyzed. The thickness of the electric double layers around the particle and cavity wall is arbitrary, and their relaxation effect is considered. Through the use of a set of linearized electrokinetic equations and a perturbation method, the ionic electrochemical potential energy, electric potential, and velocity fields in the fluid are solved with the fixed space charge density of the particle and surface charge density of the cavity as the small perturbation parameters, and an explicit formula for the sedimentation velocity is obtained. Due to the electroosmotic enhancement on the fluid recirculation in the cavity caused by the sedimentation-induced electric field, the presence of the surface charges on the cavity wall increases the sedimentation velocity of the porous particle. For the sedimentation of a porous particle in a cavity with their fixed charges of the same sign, the effect of electric interaction between the particle and cavity wall in general increases the sedimentation velocity. For the case of their fixed charges with opposite signs, the sedimentation velocity is increased/reduced if the magnitude of the fixed charge density of the cavity wall is relatively large/small. The effect of the surface charges at the cavity wall on the sedimentation of the porous particle increases with an increase in the permeability for fluid flow within the particle and with a decrease in the particle-to-cavity radius ratio (i.e., an increase in the surface area of the cavity wall relative to a given size of the particle, which enhances the fluid recirculation effect).

11.
Dis Esophagus ; 25(1): 10-6, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21595780

ABSTRACT

Muscularis externa of mouse esophagus is composed of two skeletal muscle layers in the adult. But less attention is paid to the histogenesis of the muscularis externa of the esophagus, and controversies still exist about the developmental process and the spatio-temporal expression characteristics of muscle-specific proteins during the development of esophageal muscularis externa. To further probe into the developmental pattern of muscularis externa of the mouse esophagus and the expression characteristics of different muscle-specific proteins, immunohistochemical and terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick-end labeling apoptotic staining methods are used to investigate the expression patterns of different muscle-specific proteins and to elucidate the relationship of these protein expressions with the development of muscularis externa of the mouse esophagus. Thus, an understanding of the developing esophageal muscularis externa may be important for developing therapeutic strategies for the treatment of human esophagus diseases. Serial sections of mouse embryos from embryonic day (ED) 12 to ED18, and full-length esophagi from postnatal first to 5th day were stained with monoclonal antibodies against α-smooth muscle actin (α-SMA), α-sarcomerical actin (α-SCA), desmin, and monoclonal anti-skeletal myosin (MHC), while apoptosis was determined using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling assay. The expression of α-SMA was started at ED12. During the development of ED14-ED15, α-SMA positive cells were seen extending from the walls of left three, four, and six arch arteries toward the dorsal wall of esophagus. Stronger expression of α-SCA and desmin could be detected at ED14 and ED15, expression intensity in caudal segment and inner layer was stained stronger than that of cranial segment and outer layer, but after ED16, strong expression of α-SCA and desmin was found in the outer layer of muscularis externa. Expression of MHC was first detected in the outer layer of cranial segment of muscularis externa at ED17. At ED18, MHC had extended to the level of thyroid gland, staining intensity in the outer layer and cranial segment was stronger than that of inner layer and caudal segment. One to five days after birth, the thickness of the esophageal muscle layer was obviously increased. Most of the muscle cells in the cranial segment of esophagus showed strong expression of α-SCA and clear cross striations at higher magnification. With progression toward the caudal segment, expression intensity of α-SCA became weaker, but the expression intensity of desmin was the same at different levels of esophagus. The muscle fibers were arranged densely with high expression of MHC in the cranial segment. During the development of esophageal muscularis externa, few apoptotic cells were observed. α-SMA, α-SCA, desmin, and MHC show different expression patterns. The differentiation of outer layer of esophageal muscularis externa is quicker than that of inner layer, and the caudal segment is quicker than that of the cranial segment. Besides, apoptosis may not participate in the development of esophageal muscularis externa. The smooth muscle cells from arch arteries may participate in the development of esophageal muscularis externa.


Subject(s)
Actins/metabolism , Esophagus/anatomy & histology , Esophagus/embryology , Muscle Development , Muscle, Skeletal/embryology , Animals , Antibodies, Monoclonal/metabolism , Apoptosis , Desmin/metabolism , Esophagus/metabolism , Female , Male , Mice , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Skeletal Muscle Myosins/immunology , Skeletal Muscle Myosins/metabolism , Time Factors
12.
Article in English | MEDLINE | ID: mdl-18273742

ABSTRACT

Water and sediment samples were collected from the Luan River and its 5 tributaries to determine polycyclic aromatic hydrocarbons (PAHs) concentrations in dissolved, particulate, and sediment phases. The Luan River watershed, located in northeastern Hebei province, provides water to population centers such as Tianjian and Tangshan. Sampling locations were chosen at areas not under direct influence of industrial activities to examine the "background" PAH contamination across the watershed. PAH concentrations in the dissolved, particulate, and sediment phases ranged from 11.5 ng/L to 171.5 ng/L, 152.8 ng/g. d.w. to 1372.3 ng/g d.w., and 6.7 to 1585.7 ng/g d.w., respectively. Low molecular weight PAHs (with 2 to 3 rings) dominated the dissolved and particulate phases, whereas medium and high molecular weight PAHs (with 4 to 6 rings) dominated the sediment phase. The isomer ratios of PAHs in sediments indicated that PAHs in Luan River originated from combustion processes and those PAHs underwent long-distance transport.


Subject(s)
Polycyclic Aromatic Hydrocarbons/analysis , Rivers , Water Pollutants, Chemical/analysis , China , Environmental Monitoring/methods , Geologic Sediments/chemistry , Particulate Matter/chemistry , Polycyclic Aromatic Hydrocarbons/chemistry , Solutions/chemistry
13.
Surg Technol Int ; 15: 311-6, 2006.
Article in English | MEDLINE | ID: mdl-17029190

ABSTRACT

This chapter assesses the safety of freehand placement of an infusion catheter (outer diameter, 0.3 mm) in brainstems of cynomolgus monkeys (Macaca fascicularis) for local infusion therapy. A posterior midline approach through the cerebellum and roof of the fourth ventricle was used to implant catheters into a pontine target area. Computer tomography (CT), magnetic resonance imaging (MRI), and histology were used to examine the position of the implants. The freehand placement of a catheter resulted in approximately 5-mm variations in anterior-posterior and dorsal-ventral locations of the targeted implantation site. No evidence of morbidity from the surgery, or from the infusion process was present. In conclusion, small-diameter catheters for chronic drug infusions can be implanted safely into the brainstem, an eloquent region that has been considered surgically inoperable. Infusion systems may offer a minimally invasive, generally applicable tool to provide chronic therapy for central nervous system (CNS) lesions.


Subject(s)
Antineoplastic Agents/administration & dosage , Brain Stem Neoplasms/drug therapy , Catheterization/instrumentation , Catheterization/methods , Disease Models, Animal , Infusions, Intralesional/instrumentation , Infusions, Intralesional/methods , Animals , Macaca fascicularis , Male
14.
J Neurosurg ; 102(1 Suppl): 53-8, 2005 Jan.
Article in English | MEDLINE | ID: mdl-16206734

ABSTRACT

OBJECT: The aim of this study was to investigate the optimal delivery rates of chemotherapy for the treatment of central nervous system tumors and to determine whether local delivery can lower toxicity profiles and increase target concentrations of chemotherapy. METHODS: The authors used two brain tumor models in rats. Slow (1 microl/hour) and fast (10 microl/hour) pumps were used to deliver chemotherapy--carboplatin, doxorubicin, and a high-molecular-weight transferrin-doxorubicin conjugate to the brains of normal rats and rats previously injected with F98 or 9L rat brain tumor cells. Brains were cut in 1-mm sections rostral and caudal from the infusion point. Slices were analyzed for doxorubicin and platinum by fluorescence and atomic absorption, respectively. In the normal tissues, the volume of drug distribution is generally greater at the faster flow rate. In abnormal tissues, distribution is similar at slow and fast infusion rates for low-molecular-weight drugs and greater at slow rates for a high-molecular-weight targeted toxin. CONCLUSIONS: After local administration the distribution of chemotherapy appears to be significantly influenced by tumor metabolism. Additional studies are needed to determine the optimal delivery rates for the interaction of the drug with the targeted tumor.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacokinetics , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Brain Neoplasms/drug therapy , Carboplatin/administration & dosage , Carboplatin/pharmacokinetics , Doxorubicin/administration & dosage , Doxorubicin/pharmacokinetics , Animals , Blood-Brain Barrier , Brain Neoplasms/veterinary , Disease Models, Animal , Female , Infusion Pumps , Molecular Weight , Rats , Rats, Inbred F344 , Transferrin/administration & dosage , Transferrin/pharmacokinetics
15.
Neurosurgery ; 52(5): 1169-76; discussion 1176-7, 2003 May.
Article in English | MEDLINE | ID: mdl-12699562

ABSTRACT

OBJECTIVE: We sought to develop a neurosurgical procedure to access the pons with a drug delivery device for chronic therapy and collect preliminary data on the toxicity of direct infusions of carboplatin in primates. METHODS: We made midline incisions on five cynomolgus monkeys, identified the inion, made a burr hole 2.5 cm below the inion, and inserted a catheter through the cerebellum into the roof of the pons. Pumps that infused saline for 90 days or carboplatin solutions for 30 to 35 days at 10 microl/d were placed subcutaneously in the low cervical/high thoracic region. Monkeys were assessed by computed tomography and magnetic resonance imaging, laboratory studies, daily neurological observation, postmortem examinations, and histopathology. RESULTS: Monkeys infused with saline and 82 microg of carboplatin remained neurologically intact throughout the infusion periods. Serial imaging showed that the catheter tip was in the pons and revealed no evidence of hemorrhage, edema, or migration. Two monkeys infused with up to 850 microg of carboplatin showed hyperintense magnetic resonance imaging signals at Days 15 and 18 and neurological deficits at approximately Week 3. Platinum levels greater than 10 ng/mg tissue were detected over a distance of 1 cm in tissue slices. Histopathology demonstrated significant tissue necrosis around the tip of the catheter. CONCLUSION: The pons of monkeys is safely accessed with a catheter for drug delivery by using a posterior midline approach. Clinical observations, radiographic imaging, and laboratory tests of animals infused with saline for 3 months or 0.26 mg/ml of carboplatin for 1 month were unremarkable. Neurotoxicity was seen with dose levels of 2.6 mg/ml of drug for 1 month. This procedure offers opportunities for examining the toxicity of brainstem antitumor therapy in primates.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/toxicity , Carboplatin/administration & dosage , Carboplatin/toxicity , Catheterization/methods , Infusion Pumps, Implantable , Infusions, Intralesional/methods , Nervous System Diseases/chemically induced , Neurosurgical Procedures/methods , Pons/surgery , Animals , Antineoplastic Agents/therapeutic use , Brain Stem Neoplasms/drug therapy , Brain Stem Neoplasms/pathology , Carboplatin/therapeutic use , Disease Models, Animal , Dose-Response Relationship, Drug , Macaca fascicularis , Magnetic Resonance Imaging , Male , Nervous System Diseases/pathology , Pons/pathology
16.
Int J Oral Maxillofac Implants ; 17(2): 220-4, 2002.
Article in English | MEDLINE | ID: mdl-11958404

ABSTRACT

PURPOSE: To examine the accuracy of 3 mechanical torque wrenches. MATERIALS AND METHODS: The torque outputs of the Nobel Biocare, Straumann ITI, and DynaTorq ITL mechanical torque-limiting devices were determined using a special setup on an Instron test machine. The devices were held in the test setup and oriented so that activation of the drivers caused a pure torsion effect. RESULTS: Significant differences generally existed between individual units and the target torque levels for the Nobel Biocare torque controller. DISCUSSION: The mean torque values of the ITI and ITL devices were within 10% of their respective target torque levels. Knowledge of applied torque levels to the screws that retain implant abutments and their attached prostheses is necessary to achieve optimal preload. The ITI and ITL devices tested in this study were capable of providing consistent torque at or near their respective targets. CONCLUSION: The torque output of each individual device deviated in varying degrees from target torque values.


Subject(s)
Dental Abutments , Dental Implants , Dental Instruments , Technology, Dental/instrumentation , Analysis of Variance , Dental Stress Analysis , Materials Testing , Reproducibility of Results , Torque
17.
Anat Rec ; 254(1): 135-46, 1999 01.
Article in English | MEDLINE | ID: mdl-9892427

ABSTRACT

The embryonic heart consists of five segments comprising the fast-conducting atrial and ventricular segments flanked by slow-conducting segments, i.e. inflow tract, atrioventricular canal and outflow tract. Although the incorporation of the flanking segments into the definitive atrial and ventricular chambers with development is generally accepted now, the contribution of the outflow tract myocardium to the definitive ventricles remained controversial mainly due to the lack of appropriate markers. For that reason we performed a detailed study of the pattern of expression of myosin light chain (MLC) 2a and 2v by in situ hybridization and immunohistochemistry during rat and mouse heart development. Expression of MLC2a mRNA displays a postero-anterior gradient in the tubular heart. In the embryonic heart it is down-regulated in the ventricular compartment and remains high in the outflow tract, atrioventricular canal, atria and inflow tract myocardium. MLC2v is strongly expressed in the ventricular myocardium and distinctly lower in the outflow tract and atrioventricular canal. The co-expression of MLC2a and MLC2v in the outflow tract and atrioventricular canal, together with the single expression in the atrial (MLC2a) and ventricular (MLC2v) myocardium, permits the delineation of their boundaries. With development, myocardial cells are observed in the lower endocardial ridges that share MLC2a and MLC2v expression with the myocardial cells of the outflow tract. In neonates, MLC2a continues to be expressed around both right and left semilunar valves, the outlet septum and the non-trabeculated right ventricular outlet. These findings demonstrate the contribution of the outflow tract to the definitive ventricles and demonstrate that the outlet septum is derived from outflow tract myocardium.


Subject(s)
Cardiac Myosins , Fetal Heart/metabolism , Myosin Light Chains/metabolism , Animals , Animals, Newborn , Female , Fetal Heart/embryology , Gene Expression Regulation, Developmental , Immunohistochemistry , In Situ Hybridization , Lac Operon , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Myocardium/metabolism , Myosin Light Chains/genetics , Pregnancy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar
18.
Circ Res ; 83(10): 986-94, 1998 Nov 16.
Article in English | MEDLINE | ID: mdl-9815146

ABSTRACT

Embryonic mice lacking functional Sox4 transcription factor die from cardiac failure at embryonic day (ED) 14. Heart morphogenesis in these embryos was analyzed in hematoxylin-azophlochsin or immunohistochemically stained, 3-dimensionally reconstructed serial sections between ED12 and ED14. Although Sox4 is expressed in the endocardially derived tissue of both the outflow tract and atrioventricular canal, Sox4-deficient hearts only suffer from defective transformation of the endocardial ridges into semilunar valves and from lack of fusion of these ridges, usually resulting in common trunk, although the least affected hearts should be classified as having a large infundibular septal defect. The more serious cases are, in addition, characterized by an abnormal number and position of the semilunar valve-leaflet anlagen, a configuration of the ridges typical for transposition of the great arteries (with linear rather than spiral course of both ridges and posterior position of the pulmonary trunk at the level of the valve), and variable size of the aorta relative to the pulmonary trunk. The coronary arteries always originated from the aorta, irrespective of its position relative to the pulmonary trunk. The restriction of the malformations to the arterial pole implies that the interaction between the endocardially derived tissue of the outflow tract and the neural crest-derived myofibroblasts determines proper development of the arterial pole.


Subject(s)
Disease Models, Animal , Gene Expression Regulation, Developmental , High Mobility Group Proteins/genetics , Trans-Activators/genetics , Transposition of Great Vessels/physiopathology , Actins/genetics , Animals , Aortic Valve/abnormalities , Aortic Valve/embryology , DNA-Binding Proteins/genetics , Desmin/genetics , Fibronectins/genetics , Heterozygote , High Mobility Group Proteins/deficiency , Mice , Mice, Knockout , Myosin Heavy Chains/genetics , NFATC Transcription Factors , Neural Crest/embryology , Neural Crest/metabolism , Nuclear Proteins/genetics , Pulmonary Valve/abnormalities , Pulmonary Valve/embryology , RNA, Messenger/genetics , SOXC Transcription Factors , Trans-Activators/deficiency , Transcription Factors/genetics
19.
Circ Res ; 82(3): 360-6, 1998 Feb 23.
Article in English | MEDLINE | ID: mdl-9486664

ABSTRACT

Cardiac malformation in connexin43 (CX43)-disrupted mice is restricted to the junction between right ventricle and outflow tract, even though CX43 is also expressed abundantly elsewhere. We analyzed cardiac morphogenesis in immunohistochemically and hybridohistochemically stained and three-dimensionally reconstructed serial sections of CX43-deficient embryos between embryonic day (ED) 10 and birth. The establishment of the D configuration in the ascending loop of CX43-deficient hearts is markedly retarded, so that the right ventricle retains a craniomedial position and is connected with the outflow tract by a more acute bend in ED10 and ED11 embryos. Because of the subsequent growth of the right ventricle, this condition usually evolves into a D loop, but when it persists, a "crisscross" configuration develops, with the atrioventricular cushions rotated 90 degrees, a horizontal muscular ventricular septum, and a parallel course of the endocardial ridges of the outflow tract. After ED12, large intertrabecular pouches develop at the ventricular side of both shelflike myocardial structures that support the endocardial ridges of the outflow tract, ie, at the location that was earlier characterized by the acute bend between the right ventricle and the outflow tract and that subsequently develops into the anterosuperior leaflet of the tricuspid valve. Retarded development of the D configuration in the ascending loop of the embryonic heart predisposes the myocardium at the junction of the right ventricle and outflow tract to excessive development of intertrabecular pouches during subsequent development.


Subject(s)
Connexin 43/deficiency , Heart Defects, Congenital/embryology , Heart Defects, Congenital/etiology , Animals , Connexin 43/genetics , Embryonic and Fetal Development/physiology , Female , Heart/embryology , Mice/embryology , Mice, Mutant Strains/genetics , Pregnancy
20.
Circ Res ; 82(4): 464-72, 1998 Mar 09.
Article in English | MEDLINE | ID: mdl-9506707

ABSTRACT

The outflow tract (OFT) provides the structural components forming the ventriculoarterial connection. The prevailing concept that this junction "rotates" to acquire its definitive topography also requires a concept of "counterrotation" and is difficult to reconcile with cell-marking studies. Rats between 10 embryonic days (EDs) and 2 postnatal days were stained immunohistochemically and by in situ hybridization. DNA replication was determined by incorporation of bromodeoxyuridine and apoptosis by the annexin V binding and terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling (TUNEL) assays. Starting at ED12, cardiomyocytes in the distal (truncal) part of the OFT begin to shed their myocardial phenotype without proceeding into apoptosis, suggesting transdifferentiation. Myocardial regression is most pronounced on the dextroposterior side and continues until after birth, as revealed by the disappearance of the myocardial cuff surrounding the coronary roots and semilunar sinuses and by the establishment of fibrous continuity between mitral and aortic semilunar valves. Fusion of the endocardial ridges of the truncus on late ED13 is accompanied by the organization of alpha-smooth muscle actin-and nonmuscle myosin heavy chain-positive myofibroblasts into a central whorl and the appearance of the semilunar valve anlagen at their definitive topographical position within the proximal portion of the truncus. After fusion of the proximal (conal) portion of the endocardial ridges, many of the resident myofibroblasts undergo apoptosis and are replaced by cardiomyocytes. The distal myocardial boundary of the OFT is not a stable landmark but moves proximally over the spiraling course of the aortic and pulmonary routes, so that the semilunar valves develop at their definitive topographic position. After septation, the distal boundary of the OFT continues to regress, particularly in its subaortic portion. The myocardializing conus septum, on the other hand, becomes largely incorporated into the right ventricle. These opposite developments account for the pronounced asymmetry of the subaortic and subpulmonary outlets in the formed heart.


Subject(s)
Heart/embryology , Rats, Wistar , Actins/metabolism , Animals , Apoptosis , Endocardium/cytology , Fibronectins/metabolism , Gestational Age , Heart Valves/embryology , Heart Ventricles/embryology , Histocytochemistry , Morphogenesis , Myosin Heavy Chains/metabolism , Rats
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