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Biomedical subjects

J D Chen

Publications and source records attributed to J D Chen.

At least 145 records · Page 8Linked to original sources

Re-epithelialization. Human keratinocyte locomotion.

Keratinocyte migration and proliferation both play a role in covering skin wounds by the process of re-epithelialization. Connective tissue components are a powerful influence on keratinocyte locomotion. The mechanisms of keratinocyte locomotion and cellular division are independent. Both connective tissue components and soluble factors may serve to enhance keratinocyte migration. In addition to the field of growth factors, we would like to suggest that there should be the recognition of an entire new class of agents called migration factors.

Cell Division↗

Clinical applications of electrogastrography.

Recently, electrogastrography (EGG) has received more and more attention. While gastroenterologists are interested in its clinical applications, concerns remain regarding the reliability and analysis of the EGG and the correlation between the EGG and gastric motility. The aims of this paper are to address these concerns and to review the potential clinical applications of the EGG. The following areas are discussed, based on the literature and our own experience with EGG: the refined method for the measurement of the EGG, the advanced techniques for quantitative analyses of the EGG, the reliability of the EGG in measuring gastric myoelectrical activity, the correlation between the EGG and gastric motility, and applications of the EGG in clinical gastroenterology.

Electrodiagnosis↗

Mechanism of human keratinocyte migration on fibronectin: unique roles of RGD site and integrins.

The migration of human keratinocytes over the wound bed plays an important role in the re-epithelialization of cutaneous wounds. Fibronectin, a large glycoprotein matrix component that is abundant within cutaneous wound beds, promotes keratinocyte migration. However, the mechanisms by which keratinocytes migrate over fibronectin are unknown. In this study, we sought to identify specific sites within the fibronectin molecule that induce keratinocyte locomotion and to characterize the cell surface receptors involved. The data show that the domain within the fibronectin molecule that induces human keratinocyte migration is the 120 kD cell-binding domain close to the carboxyl terminus. The 40 kD heparin-binding domain near the carboxyl terminus and the 45 kD gelatin-binding domain near the amino terminus did not promote keratinocyte migration. In addition, keratinocyte migration on both fibronectin and the 120 kD cell-binding domain was completely inhibited by the presence of GRGDSP peptide, suggesting that keratinocyte migration on fibronectin is mediated by recognizing the RGD sequence located within the cell-binding domain of fibronectin. Furthermore, keratinocytes were able to migrate directly on immobilized RGD substratum. Cell migration on fibronectin is mediated by the alpha 5 beta 1 integrin since antibodies blocking the alpha 5 and the beta 1 subunits completely inhibited keratinocyte migration on fibronectin. In addition, we demonstrate that human keratinocytes express alpha 5 beta 1 integrin in culture by flow cytometry.

Binding Sites↗

Conserved DNA binding and self-association domains of the Drosophila zeste protein.

The zeste gene product is involved in two types of genetic effects dependent on chromosome pairing: transvection and the zeste-white interaction. Comparison of the predicted amino acid sequence with that of the Drosophila virilis gene shows that several blocks of amino acid sequence have been very highly conserved. One of these regions corresponds to the DNA binding domain. Site-directed mutations in this region indicate that a sequence resembling that of the homeodomain DNA recognition helix is essential for DNA binding activity. The integrity of an amphipathic helical region is also essential for binding activity and is likely to be responsible for dimerization of the DNA binding domain. Another very strongly conserved domain of zeste is the C-terminal region, predicted to form a long helical structure with two sets of heptad repeats that constitute two long hydrophobic ridges at opposite ends and on opposite faces of the helix. We show that this domain is responsible for the extensive aggregation properties of zeste that are required for its role in transvection phenomena. A model is proposed according to which the hydrophobic ridges induce the formation of open-ended coiled-coil structures holding together many hundreds of zeste molecules and possibly anchoring these complexes to other nuclear structures.

Amino Acid Sequence↗

The relation between motor evoked potential and clinical motor status in stroke patients.

Forty-one stroke patients and 41 normal controls of matched age, sex and body height were studied by magnetic stimulation of the motor cortex and lower cervical area. The cortical and cervical motor evoked potentials (MEPs) were detected from the abductor pollicis brevis muscle. The amplitudes and latencies of cortical MEPs, central conduction time (CCT), and interside difference of bilateral CCT (DCCT) in stroke patients showed significant difference in comparison with normal controls. The degree of motor weakness was statistically correlated with the severity of cortical MEP findings, but not with the deep tendon reflex and Babinski sign. The abnormal rate of cortical MEP was higher in patients with hemorrhage than in those with infarction. Six out of 17 patients with hemorrhage had prolonged CCT or DCCT, but only 3 out of 24 patients with infarction had the same findings. The cortical MEP findings in putaminal hemorrhage were more severe than in thalamic hemorrhage. In instances of infarction involving total middle cerebral artery territory (cortical and subcortical areas), the cortical MEP was absent in all cases (4/4). It was concluded that cortical MEP findings in stroke patients examined by magnetic stimulation showed good correlation both with the lesion radiologically and the motor deficit clinically. This is an acceptable method for quantitative evaluation of motor system function in stroke.

Adult↗

Effects of dietary zinc on free radical generation, lipid peroxidation, and superoxide dismutase in trained mice.

The purpose of this study was to investigate the effects of dietary zinc on free radical generation, lipid peroxidation, and superoxide dismutase (SOD) in exercised mice. In the first part of the study, 48 male weanling mice were randomly divided into three groups. They were fed a zinc-deficient diet containing 1.6 mg/kg zinc or were pair-fed or fed ad libitum a zinc-adequate diet supplemented with 50 mg/kg zinc. Half of each group received an exercise training program that consisted of swimming for 60 min per day in deionized water. The diets and exercise program persisted for 6 weeks. In the second part of the study, 64 mice were fed zinc-deficient diets for 6 weeks, and then one group was fed the zinc-deficient diet for an additional 3 weeks, and the other three groups were fed diets supplemented with 5, 50, and 500 mg/kg zinc, respectively. Half of each group also received the exercise program. Both blood and liver samples were examined. Free radicals in liver were directly detected by electron spin resonance techniques and the extent of lipid peroxidation was indicated by malonic dialdehyde (MDA). Both CuZn-SOD and Mn-SOD were measured. The results showed that exercise training increased the metabolism of zinc, and zinc deficiency induced an increased free radical generation and lipid peroxidation and a decreased hepatic CuZn-SOD activity in exercised mice. Furthermore, although exercise training had no effect on the level of free radicals in zinc-adequate mice, it could increase the hepatic mitochondrial MDA formation further in zinc-deficient animals and zinc deficiency would eliminate the exercise-induced increase in SOD activities which existed in zinc-adequate mice. A total of 50 mg/kg zinc supplemented in the diet was adequate to correct the zinc-deficient status in exercised mice while 5 mg/kg zinc had a satisfactory effect on the recovery of only sedentary zinc-deficient mice. However, 500 mg/kg zinc had a harmful effect on both sedentary and exercised zinc-deficient animals.

Analysis of Variance↗

Role of uracil-DNA glycosylase in mutation avoidance by Streptococcus pneumoniae.

Uracil-DNA glycosylase activity was found in Streptococcus pneumoniae, and the enzyme was partially purified. An ung mutant lacking the activity was obtained by positive selection of cells transformed with a plasmid containing uracil in its DNA. The effects of the ung mutation on mutagenic processes in S. pneumoniae were examined. The sequence of several malM mutations revertible by nitrous acid showed them to correspond to A.T----G.C transitions. This confirmed a prior deduction that nitrous acid action on transforming DNA gave only G.C----A.T mutations. Examination of malM mutant reversion frequencies in ung strains indicated that G.C----A.T mutation rates generally were 10-fold higher than in wild-type strains, presumably owing to lack of repair of deaminated cytosine residues in DNA. No effect of ung on mutation avoidance by the Hex mismatch repair system was observed, which means that uracil incorporation and removal from nascent DNA cannot be solely responsible for producing strand breaks that target nascent DNA for correction after replication. One malM mutation corresponding to an A.T----G.C transition showed a 10-fold-higher spontaneous reversion frequency than other such transitions in a wild-type background. This "hot spot" was located in a directly repeated DNA sequence; it is proposed that transient slippage to the wild-type repeat during replication accounts for the higher reversion frequency.

Base Composition↗

Complex formation between the lymphotropic papovavirus large tumor antigen and the tumor suppressor protein p53.

The simian B-lymphotropic papovavirus (LPV) encodes a large tumor antigen (T antigen) which is 45% identical to both the simian virus 40 (SV40) and the polyomavirus (PyV) large T antigens. In transgenic mice, the transforming properties of the LPV T antigen are similar to those of the SV40 T antigen. However, little is known about its biochemical activities. Since SV40 T antigen forms a complex with and stabilizes the host cell tumor suppressor protein p53 while the PyV large T antigen does not, we characterized the LPV T antigen for its ability to complex p53. We demonstrate an association between LPV T antigen and p53 in both a tumor-derived cell line and BALB/c 3T3 cells transformed in culture. A third protein of approximately 68 kDa which was found associated with the LPV T antigen-p53 complex in tumor-derived cells appears to be heat shock protein 70 (hsp70). The half-life of p53 in all LPV T-antigen-transformed cells was extended significantly; i.e., it was 3 to 7 h compared with 19 minutes in BALB/c 3T3 cells. The half-life of the LPV T antigen itself was 5 to 9 h depending on the cell line origin. That p53 was stabilized because of association with LPV T antigen and not because of mutation was demonstrated with the p53 conformation-dependent monoclonal antibody PAb246. This antibody distinguishes between wild-type p53 (PAb246+) and mutant, oncogenic p53 (PAb246-). Sequential immunoprecipitation showed all detectable p53 to be of the PAb246+ class in each LPV-transformed cell line, suggesting that the stable p53 was indeed wild type.

Amino Acid Sequence↗

Uniform cell-autonomous tumorigenesis of the choroid plexus by papovavirus large T antigens.

The simian virus 40 (SV40) large tumor antigen (T antigen) under its natural regulatory elements induces choroid plexus papillomas in transgenic mice. Because these tumors develop focally after several months, it has been suggested that secondary cellular alterations are required to induce a tumor in this tissue. In contrast to SV40, the related lymphotropic papovavirus early region induces rapid nonfocal choroid plexus neoplasia in transgenic mice. Here, using hybrid gene constructs, we showed that T antigen from either virus in in fact sufficient to induce these tumors. Their abilities to induce proliferative abnormalities in other tissues, such as kidney and thymus, were also indistinguishable. Differences in the rate of choroid plexus tumorigenesis reflected differences in the control regions of the two viruses, rather than differences in T antigen per se. Under SV40 regulation, expression was limited to a fraction of the choroid plexus cells prior to the formation of focal tumors. When SV40 T antigen was placed under lymphotropic papovavirus control, in contrast, expression was generally uniform in the choroid plexus and rapid expansion of the tissue ensued. We found a direct relationship between T-antigen expression, morphological transformation, and proliferation of the choroid plexus epithelial cells. Analysis of mosaic transgenic mice indicated further that T antigen exerts its mitogenic effect cell autonomously. These studies form the foundation for elucidating the role of various T-antigen subactivities in tumorigenesis.

Animals↗

Exposure to mixtures of solvents among paint workers and biochemical alterations of liver function.

The objective of this study was to determine biochemical alterations of liver function among paint manufacturers and sprayers associated with exposure to organic solvents. Two paint manufacturing factories and 22 various kinds of spray painting factories (16 car painting, two aircraft painting, three video terminal painting; and one trailer painting) were included. Air concentrations of organic solvents were collected by personal samplers and analysed by gas chromatography. A total of 180 workers were given a comprehensive physical examination, a questionnaire, a liver function test, and a test for hepatitis B surface antigen. The questionnaire contained questions regarding detailed personal medical history, intake of alcohol, and use of medicine. Mixtures of solvents were used throughout the factories, and xylene and toluene were the major components found in almost all air samples with average contents of 46% and 29% on a weight basis of 67 air samples. No strong hepatotoxic solvents were detected. Workers were classified according to the different exposure patterns and different air concentrations of breathing zones as: high (eight hour time weighted average (8 h TWA) hygienic effects of solvents 0.25-9.83, median 1.66), short term high (8 h TWA hygienic effects of solvents 0-3.38, median 0.12), and low (8 h TWA hygienic effects of solvents all below 0.38). After applying a multivariate model to control the non-occupational factors (alcohol, medication, age, and hepatitis B viral infection), increase in gamma-glutamyl transferase (GGT) activity was found to be associated with severity of exposure to the mixture of solvents. Because the possible effects on GGT activity of non-occupational factors were controlled for, it is concluded that increased GGT activity among exposed workers may be due to a higher exposure to the mixture of solvents.

Adult↗

Clinical variability in a family with X-linked retinal dystrophy and the locus at the RP3 site.

One large Australian family with X-linked retinal dystrophy was found to have extreme clinical variability in the hemizygotes. One member had the typical rod-cone disease, three had the cone-rod pattern and one had macroscopic changes in the macular area only, but with low potentials in the ERG. The locus for the disease was found to be distal to L1.28 at Xp21, the site for RP3. From a study of case histories reported it seems that clinical variability can be a common feature of X-linked retinitis pigmentosa (XLRP) with the locus at Xp11.3 (RP2) or at Xp21 (RP3), and this family may well be categorized as XLRP.

Adult↗

Distinct positive and negative elements control the limited hepatocyte and choroid plexus expression of transthyretin in transgenic mice.

Transthyretin (TTR) is a thyroid hormone transport protein that is secreted by hepatocytes into the serum and by the choroid plexus epithelium into the cerebral spinal fluid. The protein is not made elsewhere in adult animals in significant amounts. We find that the start site for mRNA synthesis is the same in both cell types. The sequences required for mouse TTR expression in cultured hepatocytes include an enhancer at -1.86 to -1.96 kbp and a promoter-proximal region at -70 to -200 bp relative to the mRNA cap site. We demonstrate that in transgenic mice these regulatory regions (approximately 300 bp) are sufficient for quantitatively normal expression of a TTR minigene in hepatocytes, but not for restricted expression in the choroid plexus cells of the brain. Instead, they direct aberrant widespread expression in regions of the brain outside the choroid plexus. With 3 kbp of upstream sequence the TTR minigene is expressed specifically in the choroid plexus as well as in the liver, demonstrating the normal cell type specificity for TTR. These results suggest that 3 kbp of upstream sequence contains positive element(s) required for choroid plexus expression which are distinct from those utilized in the hepatocyte, and may also contain negative element(s) that function to suppress transcription in other brain cell types.

Animals↗

Inhibition of human cancer cell growth by periodate-oxidized 3-aminopyridine adenine dinucleotide phosphate.

1. Periodate-oxidized 3-aminopyridine-adenine dinucleotide phosphate inhibited the proliferation of oral epithelium cancer and breast cancer cell lines. 2. The fast growing less differentiated embryonic kidney cell was more affected by the reagent then the embryonic lung fibroblast cell. 3. Incorporation of [3H]leucine of the treated cancer cells was inhibited. Incorporation of [3H]uridine was increased. Incorporation of [3H]thymidine was first increased and then decreased. 4. Tumor malic enzyme activity was inhibited by the reagent; but the treated cells did not show any difference in malic enzyme or glucose-6-phosphate dehydrogenase levels.

Adenine Nucleotides↗

Localizing multiple X chromosome-linked retinitis pigmentosa loci using multilocus homogeneity tests.

Multilocus linkage analysis of 62 family pedigrees with X chromosome-linked retinitis pigmentosa (XLRP) was undertaken to determine the presence of possible multiple disease loci and to reliably estimate their map location. Multilocus homogeneity tests furnished convincing evidence for the presence of two XLRP loci, the likelihood ratio being 6.4 x 10(9):1 in favor of two versus a single XLRP locus and gave accurate estimates for their map location. In 60-75% of the families, location of an XLRP gene was estimated at 1 centimorgan distal to OTC, and in 25-40% of the families, an XLRP locus was located halfway between DXS14 (p58-1) and DXZ1 (Xcen), with an estimated recombination fraction of 25% between the two XLRP loci. There is also good evidence for a third XLRP locus, midway between DXS28 (C7) and DXS164 (pERT87), supported by a likelihood ratio of 293:1 for three versus two XLRP loci.

Chromosome Mapping↗

NMR detection of creatine kinase expressed in liver of transgenic mice: determination of free ADP levels.

To use the equilibrium established by creatine kinase (CK) to determine hepatic free ADP levels, the transcriptional control elements of the transthyretin gene were used to direct expression of the CK B isozyme to the livers of transgenic mice. Activities of CK ranging from 80-250 mumol per min per g (wet weight) were detected in liver extracts from five founder mice. The CK activity was stably transmitted to subsequent generations. Isozyme gels and immunoblots confirmed that the activity detected in extracts was due to the B isozyme of CK. Immunohistology indicated that the protein was expressed uniformly throughout the liver and was localized primarily to the cytoplasm. 31P NMR spectroscopy was used to detect the metabolic product of the CK reaction, phosphocreatine, demonstrating that the enzyme was active in vivo. The phosphocreatine level fell rapidly during anoxia (t1/2 = 1 min), indicating that the CK reaction was integrated into hepatic energy metabolism. The equilibrium established by CK was used to calculate a hepatic free ADP level of 0.059 +/- 0.004 mumol/g (wet weight). In vivo NMR studies of these mice will be valuable for studying the role of free ADP in regulating liver metabolism.

Adenosine Diphosphate↗

Multichannel adaptive enhancement of the electrogastrogram.

The electrogastric signal can be measured cutaneously on the abdomen. This is attractive because it is harmless to patients or volunteers. However, the poor quality of the cutaneous measurements necessitates signal enhancements. Hence, in this paper, an adaptive multichannel signal enhancing system is proposed. The mu-vector least mean square (LMS) algorithm is applied to adjust the weights of the adaptive filters in the system. The detailed description and the performance analysis of the system is given in the paper. Applying the proposed system, the respiratory artifact, the electrode-skin noise, some of motion artifacts, and the electrocardiography (ECG) can be efficiently reduced while the characteristics of the relevant gastric signal is less affected.

Adaptation, Physiological↗

[Drug interaction between digoxin and bisacodyl].

Digoxin is one of the inotropic agents commonly used to improve cardiac performance in patients with congestive heart failure and to control ventricular response in atrial fibrillation and other supraventricular tachycardias. Bisacodyl (dulcolax), a stimulant laxative, is also commonly prescribed to prevent straining at stool or constipation in these patients. Therapeutic monitoring of digoxin is helpful in the evaluation of clinical response and intoxication of digoxin. For the convenience of serum level measurement, digoxin is usually administered at night before sleep to allow ample time for tissue distribution and then blood sampling the next morning. Concomitant use of these drugs may increase the likelihood of drug interaction. Eleven healthy volunteers, aged 22-26, were studied within 35 days accordingly in four phases. The serum digoxin concentration (SDC) in phase 2 (digoxin and bisacodyl together) showed a significant decrease as compared with phase 1 (digoxin alone) (0.58 +/- 0.03 vs. 0.66 +/- 0.03 ng/ml, M +/- SE, p less than 0.05). The percentage of SDC changes was down to -11.7 +/- 5.4%. Phase 4 (digoxin taken 2 hours before bisacodyl) showed an increase in SDC in comparison with phase 3 (digoxin alone) but was not statistically significant (0.65 +/- 0.03 vs. 0.62 +/- 0.03 ng/ml, M +/- SE, p greater than 0.05). The average frequency of diarrhea was 3.5 times in the first day of phase 2 and 2.7 times in the first day of phase 4. We conclude that in volunteers bisacodyl interacts with digoxin resulting in reduction of the SDC. Interference of the absorption is the most likely mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗