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Biomedical subjects

M Wang

Publications and source records attributed to M Wang.

At least 901 records · Page 50Linked to original sources

Development and histology of fibrous architecture of the fetal temporomandibular joint.

The developmental history of the temporomandibular joint (TMJ) was investigated in 10 fetuses of 4 to 10 months of gestational age. The S-type structure of the disc is formed by the following bases: 1) the flat upper and concave lower surfaces of the disc; 2) thinner intermediate zone and thicker anterior and posterior bands; 3) the projection of the articular tuberculum and superoposterior growth of the condyle. The posterolateral part of the disc was the thickest and the corresponding part of the fossa was the deepest. The condyle was originally positioned beneath the part of disc that was considered the main force-bearing area. The distribution and arrangement of elastic and collagen fibers in the disc was proportional to disc function. Gross elastic fibers in the posterolateral part of the posterior band were connected with the upper head of the pterygoideus lateralis muscle fibers running medioanteriorly. They were indicated to be antagonistic with each other. At 4 months of gestational age, a few elastic fibers appeared in the bilaminar region and began to form bundles as the fetus grew. At full-term dense elastic fibers were found in the upper stratum of the bilaminar region.

Gestational Age↗

An in vitro biomechanical study of the static stabilizing effect of lateral prophylactic knee bracing on medial stability.

We attempted to determine if the selected lateral prophylactic knee braces (ie, Anderson Knee Stabler-101W, Don Joy-PKG and McDavid Knee Guard) were effective at stabilizing the medial collateral ligament against valgus loading to the knee joint. We tested 23 volunteer subjects under each of three braced conditions, plus a nonbraced condition. Applying stress to the lower leg of the subjects, we measured and recorded the linear displacement of the tibia in abduction and/or adduction. We analyzed the data, using a repeated measures ANOVA. There were no differences between the bracing conditions. We concluded that the three knee braces were not effective at stabilizing the knee joint from a static valgus force.

Journal Article↗

Prenatal diagnosis and a donor splice site mutation in fibrillin in a family with Marfan syndrome.

The Marfan syndrome, an autosomal dominant connective tissue disorder, is manifested by abnormalities in the cardiovascular, skeletal, and ocular systems. Recently, fibrillin, an elastin-associated microfibrillar glycoprotein, has been linked to the Marfan syndrome, and fibrillin mutations in affected individuals have been documented. In this study, genetic linkage analysis with fibrillin specific markers was used to establish the prenatal diagnosis in an 11-wk-gestation fetus in a four-generation Marfan kindred. At birth, skeletal changes suggestive of the Marfan syndrome were observed. Reverse transcription-PCR amplification of the fibrillin gene mRNA detected a deletion of 123 bp in one allele in affected relatives. This deletion corresponds to an exon encoding an epidermal growth factor-like motif. Examination of genomic DNA showed a G-->C transversion at the +1 consensus donor splice site.

Adult↗

[Induction of human platelet Ca2+ fluxes by anti-GP IIb/IIIa and anti-CD9 monoclonal antibodies].

Calcium plays a central role in platelet activation. Calcium changes in acquorin-loaded human platelets induced by monoclonal antibodies (McAbs) were recorded using a PIGA-apparatus. McAb Apt4 is specific for GP IIb/IIIa and McAb XW-1 and SJ-9A4 are directed against CD9 antigen. All three McAbs were shown to elicit a Ca2+ rise in aequorin-loaded platelets. This rise was the sole result of Ca2+ influx in the case of Apt4 and XW-1 and of both Ca2+ influx and mobilization in the case of SJ-9A4. Platelet Ca2+ fluxes and aggregation induced by the three McAbs were inhibited by an anti-GP IIb/IIIa McAb HIP8. The Ca2+ channel blocker vorapamil exerted a complete inhibitory effect on platelet Ca2+ fluxes and aggregation induced by Apt4, and had a partial effect on that induced by XW-1 and SJ-9A4. The ADP inhibitor CP/CPK had a partial inhibitory effect on platelet Ca2+ fluxes and aggregation induced by Apt4 and XW-1, and a smal effect on that induced by SJ-9A4. The effects of the three McAbs were inhibited partially by the calmodulin inhibitor EBB. The results indicate that platelet Ca2+ fluxes induced by these three McAbs depend on different pathways.

Antibodies, Monoclonal↗

[Protective effects of nitrendipine against myocardial infarction in rabbits].

In rabbits the left circumflex coronary artery was ligated for 24 h. Nitrendipine (Nit) 10 mg.kg-1 ig were given 1 h before ligation and 1, 4, and 7 h after ligation. Nit decreased myocardial infarctive size (MIS) from 25.2 +/- 1.7% to 15.5 +/- 1.6% (P < 0.01), lowered serum creatine kinase (CK) and lactate dehydrogenase isoenzyme 1 (LDH1) from 381 +/- 69 IU.L-1 and 42 +/- 6% to 281 +/- 49 IU.L-1 (P < 0.01) and 31 +/- 8% (P < 0.05), diminished injury of myocyte ultrastructure, especially mitochondria and myofibrillae, in ischemic and infarctive zone. Nit exerted no significant effect on plasma level of norepinephrine (NE). The results indicate that Nit has protective effects against the acute myocardial infarction.

Animals↗

Conformation changes of p53 proteins in regulation of murine T lymphocyte proliferation.

This report shows that p53 gene expression is required for proliferation of Concanavalin A (ConA)-stimulated murine T lymphocytes. p53 gene-specific antisense oligodeoxynucleotides strongly inhibited expression of p53 gene in T lymphocytes, causing suppression of ConA-induced cell proliferation. In contrast, the complementary-sense oligomers had no inhibitory effects. Northern and immunoprecipitation-blotting assay data, however, showed no change in p53 mRNA and proteins synthesized in T lymphocytes before and after ConA stimulation. p53 proteins in the resting and ConA-stimulated T cells had different immunoreactivity with specific monoclonal antibodies. p53 from resting T cells only reacted with "wild-type form" p53-specific monoclonal antibody (PAb246); whereas, p53 from ConA-stimulated T cells was recognized by "mutant-form" p53-specific monoclonal antibody (PAb421). These results suggest that the conformation of p53 proteins in resting and ConA-stimulated T cells are different. The p53 conformation changes may be related to the regulation of murine T lymphocyte proliferation.

Animals↗

Neural wave representation in early vision.

The neural wave representation which describes spatiotemporal information in early vision is proposed in terms of extended Gabor functions in this paper. Its reasonability, completeness and uncertainty in spatiotemporal domains and their frequency domains were investigated. The ranges of these parameters in this representation were estimated on electrophysiological and psychophysical data. We derived the partial differential equations which the neural wave satisfied. The general significance of 3D neural wave representation has been explored.

Animals↗

Age- and gender-related variations in the activities of drug-metabolizing and antioxidant enzymes in the white-footed mouse (Peromyscus leucopus).

The effects of aging on the activities of drug-metabolizing enzymes and antioxidant enzymes were studied in male and female White-Footed mice (Peromyscus leucopus) at ages of 6, 8, 12, 18, 24, 30, 36, and 48 months. Male mice had significantly higher liver microsomal cytochrome P450 (P450) content and NADPH:cytochrome P450 oxidoreductase (P450 reductase) activities than females at all age groups. Many of the P450-dependent enzyme activities were also generally higher in males. Female mice showed age-dependent decreases in P450 content and the activities of P450 reductase, pentoxyresorufin O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMAd) in the liver from 6 to 24 months; while, the males showed an age-dependent decrease only for the liver PROD activity from 6 to 24 months. The old males (30-month old) appeared to have significantly higher activities for 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone and androstenedione formation than the middle-aged (6- to 18-month old) and very old (48-month old) males. Females showed age-dependent decreases for the formation of 6 beta-, 2 beta-, 16 alpha- and 16 beta-testosterone in liver microsomes from 6 to 24 months. Lung microsomes from 6- and 8-month old males had much higher activities of ethoxyresorufin O-deethylase (EROD) and PROD than older males. The total NNK alpha-hydroxylation activities changed in the same pattern as lung microsomal EROD and PROD activities in both male and female mice. The activities of several phase II drug-metabolizing enzymes: glutathione S-transferase (GST), DT-diaphorase, sulfotransferase and UDP-glucuronosyl-transferase (UDPGT) did not show any significant age-dependent changes, with the possible exception that the GST activity in males decreased from 18 to 36 months. Males had about 3-fold higher UDPGT activities than females among all age groups. Glutathione peroxidase activities were drastically lower in old and very old males, and 6 to 24 months old males had significantly higher activities than the corresponding females. In females, superoxide dismutase activities decreased linearly to extremely low levels as mice aged. Catalase activities showed a tendency for increase with age in males. In conclusion, some P450-dependent activities and antioxidant enzymes, but not phase II drug-metabolizing enzymes, showed age-dependent changes; and most of these changes occur from 6 to 24 months. The demographic attributes of the White-Footed mouse are well-suited for physiological and biochemical studies of aging and can complement the more standard laboratory mouse model with its typical two year life span.

Age Factors↗

Transduction of primary human hepatocytes with amphotropic and xenotropic retroviral vectors.

Experiments in animal models suggest that it is feasible to consider hepatic gene therapy using a strategy in which hepatocytes would be isolated by partial hepatectomy, transduced with recombinant retroviral vectors containing genes of therapeutic importance, and then transplanted back into the patient by autologous hepatocellular transplantation. The application of this strategy in clinical trials will require adapting these methods to human cells. We describe the transduction of primary human hepatocytes with two forms of retroviral vectors: amphotropic vectors, which have been used previously in clinical trials, and xenotropic vectors, which have a different host range. Human hepatocytes were harvested from organs preserved in Belzer's solution and were cultivated in a serum-free, tyrosine-free, hormonally defined medium. These cells proliferated for 3-5 days in culture, exhibited characteristic hepatocyte morphology, and expressed liver-specific functions, including phenylalanine hydroxylase, alpha 1-antitrypsin, and glutamine synthase. Transduction with an amphotropic LNL6 retroviral vector resulted in stable incorporation of the provirus into 1% of the cells as estimated by semiquantitative PCR. Consistently higher transduction efficiencies (as much as 10% of the cells) were observed with a xenotropic N2 vector. These data support the feasibility of using LNL6 as a marker gene in clinical trials of hepatocellular transplantation. These data also suggest that the efficiency of transducing hepatocytes with amphotropic vectors in animal models may not accurately reflect the utility of these vectors for human applications. Consideration should be given to the use of xenotropic vectors for optimizing the efficiency of transduction for human applications.

Animals↗

The human loricrin gene.

Loricrin is the major protein component of the cornified cell envelope of terminally differentiated mammalian epidermal (stratum corneum) cells. Using a specific human cDNA clone, we have isolated and characterized the human loricrin gene. We show that it has a very simple structure of a single intron of 1188 base pairs (bp) in the 5'-untranslated region; there are no introns in coding sequences. By use of rodent-human somatic cell hybrids, followed by in situ hybridization with a biotin-labeled genomic DNA clone, the single-copy gene maps to chromosome location 1q21. Polymerase chain reaction analyses of genomic DNAs from different individuals show that human loricrin consists of two allelic size variants, due to sequence variations in its second glycine loop domain, and these variants segregate in the human population by normal Mendelian mechanisms. Furthermore, there are multiple sequence variants within these two size class alleles due to various deletions of 12 bp (4 amino acids) in the major loop of this glycine loop domain. By use of a specific loricrin antibody, we show by immunogold electron microscopy that loricrin initially appears in the granular layer of human epidermis and forms composite keratohyalin granules with profilaggrin, but localizes to the cell periphery (cell envelope) of fully differentiated stratum corneum cells.

Amino Acid Sequence↗

Taxol blocks processes essential for prostate tumor cell (PC-3 ML) invasion and metastases.

We have examined the antimetastatic effects of taxol on a PC-3 human prostatic tumor variant (PC-3 ML) which metastasizes to the lumbar vertebrae in severe combined immunodeficiency-carrying (SCID) mice. Immunofluorescence labeling indicated that taxol (0.5 to 1.0 microM for 6 h) produced an abnormal bundling of microtubules in a dosage-dependent manner. Slot blotting and gelatinase assays revealed that taxol inhibited secretion of the M(r) 72,000 and M(r) 92,000 type IV collagenases plus a M(r) 57,000 gelatinase. Radioimmunoprecipitation measurements confirmed that the drug inhibited both the secretion and the synthesis of the M(r) 72,000 collagenase. Taxol also blocked total protein secretion but did not influence total protein synthesis or turnover. Boyden chamber chemotactic studies further showed that taxol (0.5 to 1.0 microM) inhibited invasion of Matrigel. More importantly, studies in SCID mice demonstrated that taxol (50 to 250 mg/m2/day) blocked the establishment, growth, and long-term survival of PC-3 ML cells.

Alkaloids↗

Structure and organization of the human transglutaminase 1 gene.

Membrane-associated transglutaminases (TGase1) have recently been found to be common in mammalian cells, but it is not clear whether these derive from the same or different genes. In order to determine the complexity of this system, we have isolated and characterized the human gene (TGM1). The gene of 14,133 base pairs was found to contain 15 exons spliced by 14 introns. Interestingly, the positions of these introns have been conserved in comparison with the genes of two other transglutaminase-like activities described in the literature, but the TGM1 gene is by far the smallest characterized to date because its introns are relatively smaller. On the other hand, the TGase1 enzyme is the largest known transglutaminase (about 90 kDa), apparently because its gene acquired tracts that encode additional sequences on its amino and carboxyl termini that confer its unique properties. Southern blot analyses of total human genomic DNA cut with several restriction enzymes reveal only one band. Use of human-rodent cell hybrid panels and chromosomal in situ hybridization with biotin-labeled probes revealed that the human TGM1 gene maps to chromosome position 14q11.2-13. Such data suggest there is a single gene copy per haploid human genome. Comparisons of sequence identities and homologies indicate that the transglutaminase family of genes arose by duplications and subsequent divergent evolution from a common ancestor but later became scattered in the human genome. Although our present Southern blot and chromosomal localization studies revealed no restriction fragment length polymorphisms, comparisons of published sequences and our genomic clone indicate there are two sequence variants for TGase1 within the human population. The rare smaller variant contains a two-nucleotide deletion near the 5'-end, uses an alternate initiation codon, and differs from the common larger variant only in the first 15 amino acids. Furthermore, the DNA sequences of intron 14 possess several tracts of dinucleotide repeats that by polymerase chain reaction analysis show wide size polymorphism within the human population. Accordingly, this gene system constitutes a useful polymorphic marker for genetic linkage analyses.

Amino Acid Sequence↗

Computational fluid dynamics of left ventricular ejection.

The present investigation addresses the effects of simple geometric variations on intraventricular ejection dynamics, by methods from computational fluid dynamics. It is an early step in incorporating more and more relevant characteristics of the ejection process, such as a continuously changing irregular geometry, in numerical simulations. We consider the effects of varying chamber eccentricities and outflow valve orifice-to-inner surface area ratios on instantaneous ejection gradients along the axis of symmetry of the left ventricle. The equation of motion for the streamfunction was discretized and solved iteratively with specified boundary conditions on a boundary-fitted adaptive grid, using an alternating-direction-implicit (ADI) algorithm. The unsteady aspects of the ejection process were subsequently introduced into the numerical simulation. It was shown that for given chamber volume and outflow orifice area, higher chamber eccentricities require higher ejection pressure gradients for the same velocity and local acceleration values at the aortic anulus than more spherical shapes. This finding is referable to the rise in local acceleration effects across the outflow axis. This is to be contrasted with the case of outflow orifice stenosis, in which it was shown that it is the convective acceleration effects that are intensified strongly.

Algorithms↗

Characterization of a new avian-like influenza A virus from horses in China.

In March 1989 a severe outbreak of respiratory disease occurred in horses in the Jilin and Heilongjiang provinces of Northeast China that caused up to 20% mortality in some herds. An influenza virus of the H3N8 subtype was isolated from the infected animals and was antigenically and molecularly distinguishable from the equine 2 (H3N8) viruses currently circulating in the world. The reference strain A/Equine/Jilin/1/89 (H3N8) was most closely related to avian H3N8 influenza viruses. Sequence comparisons of the entire hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix (M), and NS genes along with partial sequences of the three polymerase (PB1, PB2, PA) genes suggest that six of the eight gene segments (PA, HA, NP, NA, M, NS) are closely related to avian influenza viruses. Since direct sequence analysis can only provide a crude measure of relationship, phylogenetic analysis was done on the sequence information. Phylogenetic analyses of the entire HA, NP, M, and NS genes and of partial sequences of PB1, PB2, and PA indicated that these genes are of recent avian origin. The NP gene segment is closely related to the gene segment found in the newly described H14 subtype isolated from ducks in the USSR. The A/Equine/Jilin/1/89 (H3N8) influenza virus failed to replicate in ducks, but did replicate and cause disease in mice on initial inoculation and on subsequent passaging caused 100% mortality. In ferrets, the virus caused severe influenza symptoms. A second outbreak of influenza in horses in Northeast China occurred in April 1990 in the Heilongjiang province with 48% morbidity and no mortality. The viruses isolated from this outbreak were antigenically indistinguishable from those in the 1989 outbreak and it is probable that the reduced mortality was due to the immune status of of the horses in the region. No influenza was detected in horses in Northern China in the spring, summer, or fall of 1991 and no influenza has been detected in horses in adjacent areas. Our analysis suggests that this new equine influenza virus in horses in Northeast China is the latest influenza virus in mammals to emerge from the avian gene pool in nature and that it may have spread to horses without reassortment. The appearance of this new equine virus in China emphasizes the potential for whole avian influenza viruses to successfully enter mammalian hosts and serves as a model and a warning for the appearance of new pandemic influenza viruses in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗