Biomedical subjects
F He
Publications and source records attributed to F He.
Morphology of developing rat genioglossal motoneurons studied in vitro: changes in length, branching pattern, and spatial distribution of dendrites.
The aim of this study is to describe the postnatal change in dendritic morphology of those motoneurons in the hypoglossal nucleus that innervate the genioglossus muscle. Forty genioglossal (GG) motoneurons from four age groups (1-2, 5-6, 13-15, and 19-30 postnatal days) were labeled by intracellular injection of neurobiotin in an in vitro slice preparation of the rat brainstem and were reconstructed in three-dimensional space. The number of primary dendrites per GG motoneuron was approximately 6 and remained unchanged with age. The development of these motoneurons from birth to 13-15 days was characterized by a simplification of the dendritic tree involving a decrease in the number of terminal endings and dendritic branches. Motoneurons lost their 6th-8th order branches, in parallel with an elongation of their terminal dendritic branches maintaining the same combined dendritic length. The elongation of terminal branches was attributed to both longitudinal growth and the apparent lengthening caused by resorption of distal branches. The elimination of dendritic branches tended to increase the symmetry of the tree, as revealed by topological analysis. Later, between 13-15 days and 19-30 days, there was a reelaboration of the dendritic arborization returning to a configuration similar to that found in the newborn. The length of terminal branches was shorter at 19-30 days, while the length of preterminal branches did not change, suggesting that the proliferation of branches at 19-30 days takes place in the intermediate parts of terminal branches. The three-dimensional distribution of dendrites was analyzed by dividing space into six equal volumes (hexants). This analysis revealed that GG motoneurons have major components of their dendritic tree oriented in the lateral, medial, and dorsal hexants. Further two-dimensional polar analysis (consisting of eight sectors) revealed a reconfiguration of the tree from birth up to 5-6 days involving resorption of dendrites in the dorsal, dorsomedial, and medial sectors and growth in the lateral sector. Later in development (between 13-15 days and 19-30 days), there was growth in all sectors, but of a greater magnitude in the dorsomedial, medial, and dorsolateral sectors.
Relationships between biomarkers of exposure and neurological effects in a group of workers exposed to acrylamide.
A study was performed among 41 workers heavily exposed to a mixture of acrylamide and acrylonitrile in the city of Xinxiang, Henan province, People's Republic of China. The workers underwent a complete medical and neurological examination and provided blood and urine for the determination of several biomarkers of exposure. Among the exposed workers, signs and symptoms indicating peripheral neuropathy were found with statistically significant increased frequencies compared to a group of controls from the same city. Based on neuropathic signs and symptoms and quantifiable indicators of peripheral nervous dysfunction, such as vibration thresholds and electroneuromyography measurements, a neurotoxicity index (NIn) specific for acrylamide-induced peripheral neuropathy was designed. The NIn, which adequately predicted the clinical diagnosis of peripheral neuropathy, was significantly correlated with the levels of mercapturic acids in 24-hr urine, hemoglobin adducts of acrylamide, accumulated in vivo doses of acrylamide, employment time, and vibration sensitivity. The NIn was correlated also with hemoglobin adducts of acrylonitrile, which was explained primarily by a correlation between acrylamide and acrylonitrile exposure in this workshop. However, it was not significantly correlated with momentary measures of exposure such as concentrations of acrylamide in the air or in the plasma of exposed workers. This study is the first in which adduct monitoring has been applied to the same group of individuals in which adverse health effects have been observed. The results seem to indicate that hemoglobin adducts are useful as predictors of acrylamide-induced peripheral neuropathy and that measurements of vibration thresholds are useful for identifying early neurotoxic effects in workplaces with hazardous exposures to acrylamide.
Nonsense-mediated mRNA decay in yeast.
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[Evaluation of the clinical acute electrophysiological effects of propafenone using transesophageal atrial pacing].
The clinical acute electrophysiological effects of propafenone were evaluated using transesophageal atrial pacing (TEAP) in 65 patients with various arrhythmias. The mean age of the patients was 41 years. Incremental pacing and programmed ectopic stimulation were performed on each patient before and during drug administration. Propafenone was given as a bolus injection of 1.5mg.kg-1 body weight followed by drip infusion at a rate of 1 mg.min-1. S-R, P wave, P-R and QRS intervals were prolonged from 194.43 +/- 21.59, 97.49 +/- 10.92, 148.00 +/- 16.20 and 82.21 +/- 7.18ms 223.00 +/- 29.25, 100.22 +/- 10.60, 166.60 +/- 20.10 and 86.54 +/- 7.19ms, respectively (P < 0.005), A-V conduction system effective refractory period (AVCSERP) was prolonged from 316.35 +/- 82.97ms to 360.31 +/- 82.67ms (P < 0.0001) in the treated group. There was no change of atrial ERP and QTc interval (P > 0.05). Fast and slow pathway ERP was prolonged by 13% and 28% of the control value, respectively (P < 0.015), and accessory pathway ERP was prolonged from 278.89 +/- 27.13ms to 305.56 +/- 33.58ms (P < 0.001), in the treated group. Sinus cycle length, corrected sinus nodal recovery time and total sinus-atrial conductive time were significantly prolonged (P < 0.0001). The results can partially explain the antiarrhythmic effects and the side effects of propafenone. TEAP is dependable in evaluating the clinical electrophysiological effects of drugs.
[Pharmacological actions of hyphae body of Auricularia auricula (L. ex Hook) Underw and its alcoholic extract].
The percent peripheral blood T lymphocytes were elevated and HC50 reduction induced by cyclophosphamide was recovered after the hyphae body of Auricularia auricula had been ip administered in mice. The action of blood platelet agglutination in rats induced by ADP was inhibited and the time of erythrocytic electrophoresis in mice was shortened after the alcoholic extract had been ig administered.
A pathologist-designed imaging system for anatomic pathology signout, teaching, and research.
Pathology images are derived from gross surgical specimens, light microscopy, immunofluorescence, electron microscopy, molecular diagnostic gels, flow cytometry, image analysis data, and clinical laboratory data in graphic form. We have implemented a network of desktop personal computers (PCs) that allow us to easily capture, store, and retrieve gross and microscopic, anatomic, and research pathology images. System architecture involves multiple image acquisition and retrieval sites and a central file server for storage. The digitized images are conveyed via a local area network to and from image capture or display stations. Acquisition sites consist of a high-resolution camera connected to a frame grabber card in a 486-type personal computer, equipped with 16 MB (Table 1) RAM, a 1.05-gigabyte hard drive, and a 32-bit ethernet card for access to our anatomic pathology reporting system. We have designed a push-button workstation for acquiring and indexing images that does not significantly interfere with surgical pathology sign-out. Advantages of the system include the following: (1) Improving patient care: the availability of gross images at time of microscopic sign-out, verification of recurrence of malignancy from archived images, monitoring of bone marrow engraftment and immunosuppressive intervention after bone marrow/solid organ transplantation on repeat biopsies, and ability to seek instantaneous consultation with any pathologist on the network; (2) enhancing the teaching environment: building a digital surgical pathology atlas, improving the availability of images for conference support, and sharing cases across the network; (3) enhancing research: case study compilation, metastudy analysis, and availability of digitized images for quantitative analysis and permanent/reusable image records for archival study; and (4) other practical and economic considerations: storing case requisition images and hand-drawn diagrams deters the spread of gross room contaminants and results in considerable cost savings in photographic media for conferences, improved quality assurance by porting control stains across the network, and a multiplicity of other advantages that enhance image and information management in pathology.
Stabilization and ribosome association of unspliced pre-mRNAs in a yeast upf1- mutant.
Nonsense-mediated mRNA decay, the accelerated turnover of mRNAs transcribed from genes containing early nonsense mutations, is dependent on the product of the UPF1 gene in yeast. Mutations that inactivate UPF1 lead to the selective stabilization of mRNAs containing early nonsense mutations but have no effect on the half-lives of almost all other mRNAs. Since the transcripts of nonsense alleles are not typical cellular constituents, we sought to identify those RNAs that comprise normal substrates of the nonsense-mediated mRNA decay pathway. Many yeast pre-mRNAs contain early in-frame nonsense codons and we consider it possible that a role of this pathway is to accelerate the degradation of pre-mRNAs present in the cytoplasm. Consistent with this hypothesis, we find that, in a strain lacking UPF1 function, the CYH2, RP51B, and MER2 pre-mRNAs are stabilized 2- to 5-fold and are associated with ribosomes. We conclude that a major source of early nonsense codon-containing cytoplasmic transcripts in yeast is pre-mRNAs and that the UPF1 protein may be part of a cellular system that ensures that potentially deleterious nonsense fragments of polypeptides do not accumulate.
Evaluation of brain function in acute carbon monoxide poisoning with multimodality evoked potentials.
The median nerve somatosensory evoked potentials (SEP), pattern reversal visual evoked potentials (VEP), and brain stem auditory evoked potentials (BAEP) were studied in 109 healthy adults and in 88 patients with acute carbon monoxide (CO) poisoning. The upper limits for normal values of peak and interpeak latencies of multimodalities of evoked potentials in the reference group were established by a stepwise multiple regression analysis. SEP changes selectively affecting N32 and N60 were found in 78.8% of patients. There was prolonged P100 latency of VEP in 58.2% of the cases examined. The prevalence of BAEP abnormalities in comatose patients (36%) was significantly higher than that (8.6%) in conscious patients. BAEP abnormalities were most frequently seen in comatose patients who had diminished brain stem reflexes (77.8%). It has been found that a consistent abnormality involving N20 and subsequent peaks in SEP, a remarkable prolongation of P100 latency in VEP, or a prolongation of III-V interpeak latency in BAEP as well as the reoccurrence of evoked potential abnormalities after initial recovery all indicate unfavorable outcomes in patients with acute CO poisoning. The multimodality evoked potentials have proved to be sensitive indicators in the evaluation of brain dysfunction and in the prediction of prognosis of acute CO poisoning and the development of delayed encephalopathy.
Determination of hemoglobin adducts in humans occupationally exposed to acrylamide.
Hemoglobin (Hb) adduct determinations were used to monitor occupational exposure to acrylamide (AA) and acrylonitrile (AN). Forty-one workers in a factory in the People's Republic of China who were involved in the synthesis of AA by catalytic hydration of AN and the manufacturing of polyacrylamides were studied. Ten nonexposed workers in the same city served as controls. AA and AN exposures were monitored using the modified Edman degradation procedure for the determination of their respective Hb adducts to N-terminal valine. The adduct levels in the exposed workers were 0.3-34 nmol/g Hb for AA and 0.02-66 nmol/g Hb for AN, as determined by gas chromatography-mass spectrometry (GC-MS). The formation of glycidamide (GA), the epoxide metabolite of AA, in humans was demonstrated by GC-MS analysis of its Hb adduct to N-terminal valine following acid hydrolysis, ion-exchange chromatography, and derivatization. The GA adduct was detected in samples from the exposed persons with levels of 1.6-32 nmol/g Hb. There was a linear relationship between the AA and GA adduct levels (r = 0.96) and the ratio of the in vivo doses of GA and AA was 3:10. These results suggest that AA is metabolized to GA in humans, as had previously been shown in the rat. The high AA adduct levels in the exposed workers, as compared to those expected from air concentrations, indicate that dermal exposure may contribute significantly to the total uptake of AA. The average daily in vivo doses of AA and GA in the highest exposed workers were comparable to the in vivo doses in rats injected with 3 mg/kg AA. Since a regimen of 2 mg/kg/day is known to cause a significant increase of tumors in rats, preventive measures may be necessary for humans exposed to high levels of AA in industrial settings.
Biological monitoring of occupational pesticides exposure.
Two kinds of measurement: (1) enzyme activities in blood, and (2) unchanged pesticides and their metabolites in urine or blood have been used in biological monitoring for assessing exposure to pesticides. The assays of acetylcholinesterase (AChE) activity in whole blood and erythrocytes are mainly applied to estimate inhibition by organophosphates (OPs) and carbamates. A level at 70% of an individual's baseline or of a mean population AChE activity has been recommended as a reference value for exposure control. The measurement of lymphocyte "neuropathy target esterase (NTE)" activity in subjects handling axonopathic OPs is mainly for research application. Analytical methods are available for detecting alkylphosphates, carbamates, pyrethroids, chlorinated hydrocarbons, some herbicides and fungicides, chlordimeform, chlorobenzilate, dichloropropene, dinitrocresol and pentochlorophenol or their metabolites in urine or blood. However, due to lack of significant dose-response or dose-effect relationship, the majority of these determinants can only be used as biological exposure indicators to confirm exposure or to estimate internal dose. Further research in developing adequate indicators and methods for biological monitoring of occupational pesticides exposure is needed. Pre-exposure value and/or reference value of relevant indicators are necessary for assessing the degree of exposure and absorption.
Quantitative measurements of vibration threshold in healthy adults and acrylamide workers.
The early detection of impaired vibration sensation is necessary in order to monitor the adverse effects in workers occupationally exposed to neurotoxic chemicals such as acrylamide. The conventional neurological examination which assesses vibration sensation by utilizing a tuning fork is relatively insensitive for this purpose. In the present study, the Vibration II, a new device for the quantitative measurement of vibration thresholds, was used in 105 healthy Chinese adults. A new testing procedure combining the "two-alternative forced-choice procedure" and the "yes-or-no method-of-limits procedure" showed good reliability and was less time consuming. The results indicate that significant differences in the vibration threshold of index fingers and great toes were found neither between males and females, nor between the left and the right side. However, there was an age-dependent increase in vibration threshold in nonexposed healthy subjects. The vibration thresholds of 41 workers exposed to acrylamide detected by the Vibration II were significantly higher than those of the healthy adults in the same age group. The quantitative measurement of vibration threshold seems to be potentially useful for screening peripheral nerve dysfunction in field studies.
Transcriptional trans activators of human and simian foamy viruses contain a small, highly conserved activation domain.
The Bel-1 protein of human foamy virus is a potent transcriptional trans activator of its homologous long terminal repeat promoter element. Here, we demonstrate that Bel-1 can also efficiently activate gene expression when targeted to a heterologous promoter by fusion to the DNA-binding motif of the yeast GAL4 protein. Analysis of a series of deletion mutants of Bel-1 generated in this hybrid protein context suggests the presence of a single transcription activation domain that is fully contained within a discrete, approximately 30-amino-acid segment located proximal to the Bel-1 carboxy terminus. Although this short motif can be shown to function effectively in eukaryotic cells of mammalian, avian, and fungal origin, it does not bear any evident sequence homology to the known classes of eukaryotic activation domain. However, this Bel-1 activation domain was found to be fully conserved, in terms of both biological activity and location, in the distantly related Taf trans activator of simian foamy virus type 1.
Functional organization of the Bel-1 trans activator of human foamy virus.
Human foamy virus encodes a 300-amino-acid nuclear regulatory protein termed Bel-1 that is required for human foamy virus replication in culture. Bel-1 is a potent trans-activator of gene expression directed by the homologous HFV long terminal repeat as well as the long terminal repeat of human immunodeficiency virus type 1. We have used mutational analysis to define several discrete functional domains within Bel-1. The C-terminal approximately 50 amino acids of Bel-1 are shown to be essential for Bel-1 activity but can be effectively substituted by the C-terminal activation domain of VP16. We therefore conclude that the Bel-1 C terminus forms part of an activation domain. Mutations within a central, approximately 100-amino-acid segment of Bel-1 preclude trans-activation by either Bel-1 or the Bel-1/VP16 chimera. These sequences are therefore proposed to direct the interaction of Bel-1 with its viral DNA target sequences. A short Bel-1 segment located between the activation and binding domains is shown to mediate the nuclear localization of this regulatory protein. Although the functional organization of Bel-1 therefore appears comparable to that reported for other eukaryotic transcriptional activators, Bel-1 does not contain sequences homologous to known transcriptional activation or DNA-binding motifs.
[Advances in research on dietary fibers].
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Human hepatic stimulator substance: a product of gene expression of human fetal liver tissue.
Cloning of human hepatic stimulator substance requires clarification of whether the substance is the product of gene expression of liver cells. In this article the translation experiment in Xenopus laevis oocytes indicates that poly (A)+ messenger RNA of human fetal liver cells could conduct the biosynthesis of human hepatic stimulator substance. The translated human hepatic stimulator substance is a heat-, acid- and alkaline-resistant, but specific hepatic-stimulating, protein with a molecular weight in the range of 10 to 30 kD and with secreting ability. The characteristics of the translated human hepatic stimulator substance are consistent with those of biochemically purified human hepatic stimulator substance from human fetal liver cells. These results demonstrate that human hepatic stimulator substance is a product of gene expression of human fetal liver cells and that the complementary DNA of human hepatic stimulator substance could be screened from the complementary DNA library of human fetal liver tissue.
A mutant of 7SL RNA in Yarrowia lipolytica affecting the synthesis of a secreted protein.
The yeast Yarrowia lipolytica contains two genes, SCR1 and SCR2, encoding a 7SL RNA associated with a signal recognition particle (SRP). To study 7SL RNA function in vivo we have systematically substituted the two conserved nucleotides G128 and A130 in loop 1 of SCR2-encoded 7SL RNA. All single mutations in either nucleotide have no effect. All double mutations are lethal except for one which results in temperature-sensitive growth. We have studied the synthesis and secretion of an alkaline extracellular protease (AEP) in both wild-type and temperature-sensitive mutant strains. Pulse-chase labeling and immunoprecipitation of this protein show that: 1) total protein synthesis is not affected in the mutant strain; 2) levels of AEP precursors in the mutant strain are 60% less than in the wild-type strain; 3) for both strains there is no accumulation of the AEP precursors in the cytoplasm; 4) the kinetics of secretion is similar. These results suggest that mutated SRP is deficient in membrane targeting but still performs translational arrest. This is consistent with the functions of SRP observed in vitro and represents the first demonstration of such roles in vivo.
The effects of burn injury on the acute phase response.
The time course of changes in the levels of acute-phase-reactant (APR) mRNAs in different tissues of rats with a 10% or a 60% total-body-surface-area (TBSA) burn and the relationship between the induction of APRs and the host's tolerance to thermal injury were studied. The acute phase response in a LPS-induced inflammation model and a burn-plus-LPS model were compared. The results of this study indicated that (1) the major site of APR synthesis is the liver; (2) even a small surface burn injury can elicit a rapid acute phase response, but the intensity of APR expression increases with the severity of the burn; (3) the down regulation of albumin mRNA, which is characteristic of the acute phase response, does not occur even though transferrin (Trf) mRNA levels are significantly decreased; (4) the resistant strain of inbred rats showed higher levels of alpha 1-antitrypsin (AT) mRNA before and after burn injury, indicating its contribution to the host's tolerance to thermal injury; (5) the increases in alpha 1-acid glycoprotein (AGP) and AT expressions are limited in the burn-plus-LPS rat model compared with either the burn model or LPS-stimulated model alone.