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Biomedical subjects

J Yu

Publications and source records attributed to J Yu.

At least 631 records · Page 35Linked to original sources
PubMed1996

In vivo observations and electron microscopy of treatment of experimental HSV keratitis with anti-HSV monoclonal antibodies.

PURPOSE: To study the antiviral activity of monoclonal antibodies (McAb) in vivo and identify their effects on experimental herpetic keratitis. METHODS: Topical use of anti-HSV monoclonal glycoprotein antibodies was carried out on acute herpetic keratitis of rabbits infected by HSV-1 SM44. The application of the eye drops in each group was five times per day for 14 days by double-blind method. In vivo observation and electron microscopy were performed during the whole procedure. The anti-HSV McAb's solution was mixed up of five monoclonal antibodies with high neutrilization titers and/or high ADCC activity. RESULTS: Compared with placebo-treated eyes, anti-HSV McAb treatment made statistically significant reduction of herpetic corneal epithelial lesion on rabbits from day 3 to day 14 postinnoculation (P < 0.01). Punctate and short dendritic lesion were the main patterns. The area of involvement was also limited. Electron microscopic analysis showed ultrastructural changes of herpetic corneal infection. The clumping of nuclear chromatin, swollon nuclei, reduction of microflament, rounding of epithelial cells were apparent in placebo-treated eyes. The advanced lesion of the viral infection was karyolysis, karyoklasis and disruption of cells in both scanning and transmission electron micrographes. The management of the McAb-treated eyes showed that the pathological involvements as mentioned above reduced remarkably. CONCLUSION: Topical application of anti-HSV monoclonal antibodies produced marked antiviral effects in inhibiting the development of experimental herpetic keratitis in rabbits and in protecting the susceptible corneal cells. As a new biological product, the anti-HSV monoclonal antibodies may provide a new approach to the treatment of HSV keratits.

Animals↗
PubMed1996

[Salvage surgery for cervical metastasis from nasopharyngeal carcinoma after radiotherapy].

One hundred and forty patients who had residual or recurrent lymph node metastasis from nasopharyngeal carcinoma after radiotherapy underwent salvage surgery. The overall 3 and 5 year survival rates were 50.1% and 27.3%, the 3 and 5 year local control rates were 48.3% and 27.3%, the 3 and 5 years distant-metastasis-free rates were 44.5% and 25.6% respectively. The most significant factors influencing survival and local control rates were the size and the involvement of the capsule of the lymph nodes. The size of the lymph node was the only influencing fastor for distant-metastasis-free survival. Distant metastasis was the most frequent factor of treatment failure (48.9%) followed by recurrence of neck mass (14.4%). The authors considered that the salvage surgery is an effective method in improving the survival rate. The reradiotherapy after surgery or/ and adjuvant chemotherapy is a new area for further investigation.

Carcinoma, Squamous Cell↗
PubMed1996

[Clinical observation on treatment of hyperinsulinemia and hyperandrogenism anovulatory patient with replenishing kidney-yin drugs].

In order to investigate the effect of Chinese herbal medicine for replenishing Kidney-Yin in treating hyperinsulinemia and hyperandrogenism anovulatory syndrome, 35 patients were treated with replenishing Kidney-Yin drugs for 3 months, basic body temperature, ultrasonic examination and blood levels of sex hormones were taken for monitoring the ovulation, and changes of serum insulin, blood sugar as well as oral glucose tolerence test were observed before and after treatment. Thirty-five patients showed high serum insulin and testosterone levels but normal dehydroepiandrosterone (DHEA) level. Twenty-nine percent of their luteinizing hormone/folliclestimulating hormone (LH/FSH) ratio were in normal range. Twenty four cases completed the regular treatment and 20 of them showed ovulation in the 43 menstrual cycles (59.7%). Seven of 17 (41.2%) infertile cases become pregnant within 6 months. After 3 months of treatment, blood sugar and insulin level significantly decreased but the latter was still slightly higher than normal level. Serum testosterone level decreased significantly and reached normal. Results suggested that replenishing Kidney-Yin Drugs could provide a good microcircumstance for ovarian follicular growth, and resulted in ovulation and pregnancy. The mechanism is remained to be further explored.

Adolescent↗
PubMed1996

Nucleotide sequences of three H-2K and three H-2D complementary DNA clones coding mouse class I MHC heavy chain proteins.

OBJECTIVES: The polymerase chain reaction (PCR)-based method was used to obtain and sequence three H-2K and three H-2D mouse complementary DNAs (cDNA) of class I major histocompatibility complex (MHC) molecules. METHODS: Messenger RNA was isolated from Conconavalin A-activated splenocytes of C57BL/10 (H-2b), C3H (H-2k), and Balb/c (H-2d) mice. We designed H-2K- and H-2D-specific primers as well as a common downstream primer based on previously published mouse class I MHC sequences. Using the PCR method and selective primers we isolated and sequenced H-2Kb and H-2Db cDNAs of C57BL/10, H-2Kk and H-2k cDNAs of C3H, as well as H-2Kd and H-2Dd cDNAs of Balb/c strains. RESULTS: Analysis of the nucleotide sequences documented similarity between our three H-2K cDNA sequences and all mouse MHC class I sequences available in the GenBank. Similarly, our three H-2D sequences were homologous with all mouse class I MHC sequences deposited in the GenBank. Our H-2K and H-2D sequences were also identical to numerous published sequences. CONCLUSIONS: Using these mouse cDNAs, we plan to determine the localization of polymorphic in vivo immunogenic amino acids in class I MHC H-2K and H-2D alloantigens.

Amino Acid Sequence↗
PubMed1995

Role of the cholinergic system in the regulation of neurotrophin synthesis.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are members of the family of neurotrophins that are highly expressed in the adult hippocampus, and to a lesser extent, in the cerebral cortex and olfactory bulb. Since neuronal expression of neutrophins is controlled by some neurotransmitters and there is a topographical correlation between neurotrophin expression and cholinergic terminal distribution from the cholinergic basal forebrain (CBF) neurons in these areas, the question arises as to whether the cholinergic system can also regulate neurotrophin gene expression in the CNS. When CBF neurons were selectively and completely destroyed by intraventricular injection of 192 IgG-saporin, resulting in a cholinergic deafferentation of the hippocampus, cortex, and olfactory bulb, there were no significant changes in NGF, BDNF and/or NT-3 mRNA levels in these areas from 1 week to 5 months after the lesion. These results suggest that afferents from CBF neurons may not play a significant role in maintaining basal levels of neurotrophin gene expression in the adult rat brain under physiological conditions. However, potential cholinergic regulation of brain neurontrophin expression may occur under other circumstances.

Animals↗
PubMed1995

GDP dissociation inhibitor serves as a cytosolic acceptor for newly synthesized and prenylated Rab5.

In vitro synthesis and post-translational prenylation of Rab5 is accomplished using reticulocyte lysate supplemented with prenyl precursors (Sanford, J. C., Pan, Y., and Wessling-Resnick, M. (1993) J. Biol. Chem. 268, 23773-23776). When Rab5 is translated in the presence of biotin-lysine-tRNA, it incorporates biotin-lysine into its peptide backbone and is efficiently prenylated; since this modification is dependent on guanine nucleotide binding, biotin-Rab5's functional integrity must be maintained. Prenylated biotin-Rab5 associates with a 45-kDa reticulocyte GDP dissociation inhibitor (GDI), sedimenting as a approximately 70-kDa particle on 5-20% sucrose density gradients. The GDI-Rab5 complex can be captured using streptavidin-linked agarose beads. Only Rab5 peptides that are substrates for prenylation are found to cosediment with the lysate GDI on sucrose gradients. Post-translational association of Rab5 and GDI is a novel finding, since previous reports suggested Rab5 remains associated with Rab escort protein (REP) after prenylation (Alexandrov, K., Horiuchi, H., Steele-Mortimer, O., Seabra, M. C., and Zerial, M. (1994) EMBO J. 13, 5262-5273). Since post-translational prenylation is catalytically mediated by REP, our study suggests that a complex between Rab5 and this factor is transient in nature. Thus, newly synthesized and prenylated Rab5 is most likely escorted to its target membrane by a GDI acceptor molecule. Biotin-Rab5 provides a novel tool for future efforts to capture and characterize additional accessory factors required for Rab protein function in vesicle transport.

Animals↗
PubMed1995

Characterization of the murine PIG-A promoter region high constitutive PIG-A gene expression in brain.

PIG-A is an X-linked gene that encodes a synthetic element required to initiate glycoinositol phospholipid (GPI) anchor assembly. In this study we characterized genomic sequence flanking the previously identified 5' end of the murine PIG-A gene and analyzed constitutive levels of PIG-A gene expression in vivo in different tissues. We found that the 5'-flanking sequence contains 1) alternative transcriptional start sites at -154 and -34/-33 relative to previously known exon 1 sequence, 2) an MRE and multiple GRE, Ap-2 and Sp-1 consensuses, and 3) a 100-bp-long GC-rich segment bounded by NF-IL6 sites. Our survey of PIG-A mRNA levels in vivo unexpectedly revealed that PIG-A expression levels are 2-4 fold higher in the brain than in other tissues.

Animals↗
PubMed1995

Comparison of the omtA genes encoding O-methyltransferases involved in aflatoxin biosynthesis from Aspergillus parasiticus and A. flavus.

O-methyltransferase (OMT) is one of the key enzymes in aflatoxin (AF) biosynthesis in the fungi, Aspergillus flavus (Af) and A. parasiticus (Ap). Genomic DNA clones containing the omtA genes from Ap strain SRRC 143 and Af strain CRA01-2B were sequenced. Comparison of the genomic DNA sequences with the cDNA of this Ap gene revealed the presence of four introns ranging from 52 to 60 bp in length in both species; the region encoding the putative S-adenosylmethionine-binding motif was located between the third and fourth introns. The coding sequence of omtA from Ap strain SRRC 143 demonstrated a greater than 97% sequence identity with that from Af strain CRA01-2B, within the coding region.

Aflatoxins↗
PubMed1995

The RNA component of human telomerase.

Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5'-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)n. Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.

Animals↗
PubMed1995

The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesis.

Aflatoxins comprise a group of polyketide-derived carcinogenic mycotoxins produced by Aspergillus parasiticus and Aspergillus flavus. By transformation with a disruption construct, pXX, we disrupted the aflatoxin pathway in A. parasiticus SRRC 2043, resulting in the inability of this strain to produce aflatoxin intermediates as well as a major yellow pigment in the transformants. The disruption was attributed to a single-crossover, homologous integration event between pXX and the recipient A. parasiticus genome at a specific locus, designated pksA. Sequence analysis suggest that pksA is a homolog of the Aspergillus nidulans wA gene, a polyketide synthase gene involved in conidial wall pigment biosynthesis. The conserved beta-ketoacyl synthase, acyltransferase and acyl carrier-protein domains were present in the deduced amino acid sequence of the pksA product. No beta-ketoacyl reductase and enoyl reductase domains were found, suggesting that pksA does not encode catalytic activities for processing beta-carbon similar to those required for long chain fatty acid synthesis. The pksA gene is located in the aflatoxin pathway gene cluster and is linked to the nor-1 gene, an aflatoxin pathway gene required for converting norsolorinic acid to averantin. These two genes are divergently transcribed from a 1.5 kb intergenic region. We propose that pksA is a polyketide synthase gene required for the early steps of aflatoxin biosynthesis.

Aflatoxin B1↗
PubMed1995

Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis.

Using gene targeting in embryonic stem cells, we have derived mice with a null mutation in a DNA mismatch repair gene homolog, PMS2. We observed microsatellite instability in the male germline, in tail, and in tumor DNA of PMS2-deficient animals. We therefore conclude that PMS2 is involved in DNA mismatch repair in a variety of tissues. PMS2-deficient animals appear prone to sarcomas and lymphomas. PMS2-deficient males are infertile, producing only abnormal spermatozoa. Analysis of axial element and synaptonemal complex formation during prophase of meiosis I indicates abnormalities in chromosome synapsis. These observations suggest links among mismatch repair, genetic recombination, and chromosome synapsis in meiosis.

Adenosine Triphosphatases↗
PubMed1995

Sustained inhibition of acetylcholinesterase activity does not disrupt early geniculocortical ingrowth to developing rat visual cortex.

Esterase activity of endogenous transiently expressed acetylcholinesterase was locally suppressed in visual cortex of infant rats for 2-5 days by the irreversible inhibitor phospholine iodide, delivered from Elvax implants. Tissue processed for anterograde movement of the carbocyanine dye DiI or anterograde transneuronal transport of wheat germ agglutinin-horseradish peroxidase revealed normal geniculocortical growth into layer IV of visual cortex. These results suggest that the catalytic activity of transiently expressed acetylcholinesterase may play little, if any, role in early development of thalamocortical systems.

Animals↗
PubMed1995

Reduction of transiently expressed acetylcholinesterase activity in developing thalamocortical projections does not affect the mature pattern of basal forebrain projections to visual cortex.

Experiments tested the hypothesis that acetylcholinesterase (AChE) activity, expressed transiently in developing thalamocortical projections, serves to limit the growth of basal forebrain cholinergic projections into thalamocortical recipient zones. Newborn rats were subjected to enucleation, a procedure that eliminates transient AChE activity in developing visual cortex. After 3-8 weeks survival, AChE histochemical techniques revealed no alteration in the pattern of AChE positive basal forebrain axons in visual cortex. These data indicate that transient AChE activity in developing sensory cortex does not limit ingrowth of basal forebrain cholinergic axons.

Acetylcholinesterase↗
PubMed1995

Cloning and characterization of the mouse PIG-A gene.

Currently there is no experimental animal model for studying paroxysmal nocturnal hemoglobinuria (PNH), an acquired hemolytic anemia linked to mutations of the PIG-A gene. In this study, we cloned and characterized the mouse PIG-A gene. Sequencing of mouse PIG-A cDNA showed that it encodes a 485 amino acid-long protein. Northern hybridizations identified a major mRNA transcript of 3.6 kb and PCR amplifications identified four smaller alternative splice products. Exon:intron junctional analyses of the mouse PIG-A genome showed 6 exons (1(> or = 60 bp), 2(780 bp), 3(133 bp) 4(133 bp), 5(207 bp), and 6(2276 bp)), the latter 5 of which encompass the coding region. Chromosomal mapping using C57BL/6J x M. Spretus backcross DNA localized the mouse PIG-A gene near the telomeric end of the mouse X chromosome. The isolation of the mouse PIG-A gene opens the possibility for the development of a mouse model of PNH.

Amino Acid Sequence↗
PubMed1995

Influence of preload reserve on stroke volume response to exercise in patients with left ventricular systolic dysfunction: a Doppler echocardiographic study.

OBJECTIVES: This study evaluated the role of preload reserve in the stroke volume response to exercise in patients with left ventricular systolic dysfunction by assessing the relation between stroke volume and late left ventricular diastolic filling during exercise. BACKGROUND: In patients with left ventricular diastolic dysfunction, the absence of left ventricular distension is the fundamental mechanism explaining the nonaugmentation of stroke volume during exercise. METHODS: In 32 patients with left ventricular systolic dysfunction and 16 healthy control subjects, mitral and aortic velocities were recorded by Doppler echocardiography at rest and during submaximal supine bicycle exercise. Stroke volume, peak early (E) and late (A) mitral velocities, A/E ratio and end-diastolic filling were measured at rest and during exercise. RESULTS: Stroke volume increased significantly in control subjects but did not change in patients. Peak early mitral velocity increased significantly and to the same extent in both groups, whereas peak late mitral velocity and end-diastolic filling increased significantly in both groups but more so in control subjects; the A/E ratio increased significantly in control subjects but did not change in patients. In addition, stroke volume correlated significantly with peak late mitral velocity during exercise in patients (r = 0.72, p < 0.001). CONCLUSIONS: Compared with control subjects, patients with left ventricular systolic dysfunction exhibited limited increases in both stroke volume and late left ventricular filling during exercise. Furthermore, their stroke volume response correlated with the capacity of the left ventricle to increase late diastolic filling, that is, preload reserve.

Adolescent↗