Biomedical subjects

Y Pan

Publications and source records attributed to Y Pan.

At least 109 records · Page 6Linked to original sources

PubMed1999

Synthesis of a chemiluminescent acridinium hydroxylamine (AHA) for the direct detection of abasic sites in DNA.

[structure: see text] The synthesis of a chemiluminescent acridinium hydroxylamine (AHA) for the direct detection of abasic sites in damaged nucleic acids is described. The reagent reacts readily with abasic sites of damaged calf thymus DNA generated in a time-dependent manner under acid/heat depurination conditions. Preliminary results indicate the sensitivity of the direct chemiluminescent detection format is approximately 0.1 abasic sites detected per 10(6) nucleotides using as little as 200 ng of DNA.

Acridines↗

PubMed1999

Retrotransposition of glycerol kinase-related genes from the X chromosome to autosomes: functional and evolutionary aspects.

Glycerol kinase catalyzes the metabolism of endogenously derived and dietary glycerol. GyK is a member of a small group of kinases termed ambiquitous enzymes, which are found either in the cytosol or as membrane-bound complexes associated with the voltage-dependent anion channel of the mitochondrial outer membrane. In Homo sapiens, the GyK gene family consists of an X-encoded locus and several X-linked and autosomal intronless retroposons, which, apparently, comprise both functional genes and processed pseudogenes. To study the role of the autosomal genes in mammalian physiology, we have isolated two murine GyK-like genes, determined their structures and chromosomal locations, and examined their functions. These sequences are intronless retroposons, which appear to be paralogues of the X-encoded, brain-specific GyK isoform and are expressed only in the testes. Though both retrotransposition events appear to have occurred prior to the primate-rodent divergence of some 65-80 million years ago, only one of the retrotransposed murine gene sequences, based upon its chromosomal location, is conserved with modern H. sapiens. To test the hypothesis that the murine GyK-like genes encode functional GyK activity, transient transfection of the gene sequences into COS7 cells was carried out. While in vitro translation confirmed that the transcripts could direct the synthesis of proteins of the appropriate size, no GyK activity was detected. Such data suggest that the autosomal GyK-like genes have evolved novel, testis-specific functions. A comparison of the human and mouse GyK-like gene sequences demonstrates the evolutionary relationships between each autosomal isoform and its corresponding X-linked ancestral locus.

Amino Acid Sequence↗

PubMed1999

Mouse monocyte-derived chemokine is involved in airway hyperreactivity and lung inflammation.

The cloning, expression, and function of the murine (m) homologue of human (h) monocyte-derived chemokine (MDC) is reported here. Like hMDC, mMDC is able to elicit the chemotactic migration in vitro of activated lymphocytes and monocytes. Among activated lymphocytes, Th2 cells were induced to migrate most efficiently. mMDC mRNA and protein expression is modulated during the course of an allergic reaction in the lung. Neutralization of mMDC with specific Abs in a model of lung inflammation resulted in prevention of airway hyperreactivity and significant reduction of eosinophils in the lung interstitium but not in the airway lumen. These data suggest that mMDC is essential in the transit/retention of leukocytes in the lung tissue rather than in their extravasation from the blood vessel or during their transepithelial migration into the airways. These results also highlight the relevance of factors, such as mMDC, that regulate the migration and accumulation of leukocytes within the tissue during the development of the key physiological endpoint of asthma, airway hyperreactivity.

Amino Acid Sequence↗

PubMed1999

The pathway regulating MDM2 protein degradation can be altered in human leukemic cells.

The MDM2 protein regulates the functional activity of the p53 tumor suppressor through direct physical association. Signals that control MDM2 expression are poorly understood but are likely to play an important role in the regulation of p53 activity. We show here that the half-life of MDM2 protein is shorter in proliferating than in quiescent peripheral blood mononuclear cells. We also demonstrate that MDM2 protein half-life is extended in some, but not all, p53 mutant human leukemic cell lines. In at least one of these p53 mutant lines, increased MDM2 protein stability is associated with higher amounts of MDM2 protein. Moreover, we demonstrate that MDM2 protein accumulates to a much greater extent in proteasome inhibitor-treated cells containing unstable MDM2 than in cells possessing stable MDM2. These results demonstrate that MDM2 expression is regulated by events that control the stability of the protein and suggest that the normal regulation of MDM2 turnover can be altered in tumor cell lines.

Burkitt Lymphoma↗

PubMed1999

Unique topology of the internal repeats in the cardiac Na+/Ca2+ exchanger.

Hydropathy analysis predicts 11 transmembrane helices in the cardiac Na+/Ca2+ exchanger. Using cysteine susceptibility analysis and epitope tagging, we here studied the membrane topology of the exchanger, in particular of the highly conserved internal alpha-1 and alpha-2 repeats. Unexpectedly, we found that the connecting loop in the alpha-1 repeat forms a re-entrant membrane loop with both ends facing the extracellular side and one residue (Asn-125) being accessible from the inside and that the region containing the alpha-2 repeat is mostly accessible from the cytoplasm. Together with other data, we propose that the exchanger may consist of nine transmembrane helices.

Animals↗

PubMed1999

Evidence for up-regulation of brain-derived neurotrophic factor mRNA by soy phytoestrogens in the frontal cortex of retired breeder female rats.

In this study, we examined the effects of oral micronized estradiol and soy phytoestrogens on the mRNA levels of brain-derived neurotrophic factor (BDNF) in the frontal cortex of ovariectomized retired breeder female rats. Fifteen ovariectomized rats were randomized into three groups and fed either a soy-free control diet (OVX), a control diet with added soybean estrogens (SBE), or a control diet with added estradiol (E2) for 8 weeks. Frontal cortex samples were collected for RNA isolation. Northern and Phosphorlmager analyses were used to determine the relative levels of BDNF mRNA. Both estradiol and soy phytoestrogens significantly increased the mRNA levels of BDNF compared to ovariectomized controls, suggesting that soy phytoestrogens may act as estrogen agonists in regulating BDNF mRNA in the frontal cortex of retired breeder female rats.

Actins↗

PubMed1999

Potent, orally bioavailable somatostatin agonists: good absorption achieved by urea backbone cyclization.

Backbone cyclization of urea-based somatostatin agonists resulted in novel, orally bioavailable agonists. Binding assays confirmed that the resulting conformationally constrained cyclic ureas retained the potency of their acyclic counterparts. SAR studies subsequently led to highly potent analogs, selective for receptor subtype 2, and having good oral bioavailability.

Administration, Oral↗

PubMed1999

Cavernous hemangiomas in the cavernous sinus. Case reports.

BACKGROUND: Extra-axial cavernous hemangiomas are rare and have a propensity to develop within the cavernous sinus. Total removal of these vascular tumors is difficult due to the risk of severe intraoperative bleeding and the complicated neurovascular structures of the cavernous sinus. Only a small number of cases have been reported to be successfully totally removed. METHODS: Retrospective studies were done in three cases of extraaxial cavernous hemangiomas located in the cavernous sinus. All three patients presented with clinical symptoms common to other tumors located in the region, such as headache and impairment of cranial nerve function. Their preoperative MRI results showed significant hyperintensity on T2-weighted images and marked enhancement with gadolinium-DTPA that delineated a sharp tumor margin. RESULTS: All three patients underwent total tumor removal, with an uneventful postoperative course. There was no postoperative neurological deficit in one patient, and a complete ophthalmoplegia and diminished sensation in the V1 distribution in two patients. Three months after operation, follow-up MRI or CT scan showed no residual tumor. CONCLUSION: Surgical resection of these lesions was possible but difficult because of severe bleeding. Avoiding piecemeal removal before the main feeding arteries are interrupted can minimize intraoperative bleeding.

Adult↗

PubMed1999

High-resolution sequence typing of HLA-DQA1 and -DQB1 exon 2 DNA with taxonomy-based sequence analysis (TBSA) allele assignment.

High-resolution DNA sequencing of exon 2 of DQA1 and DQB1 genes that uses a taxonomy-based sequence analysis (TBSA) method to assign alleles was developed. The system uses fewer primers for polymerase chain reaction (PCR) amplification and sequencing than other methods and yields accurate DQA1 and DQB1 typing when either homozygous or heterozygous DNA samples are tested. The approach was initially corroborated by the correct typing of 10 blinded samples that had been previously typed by PCR using sequence-specific oligonucleotide probes (PCR-SSOP) or serology, and subsequently confirmed by sequencing of cloned PCR products. DNA from peripheral blood cell samples of 130 individuals enrolled in a case-control analysis of HLA determinants of abdominal aortic aneurysm were subsequently evaluated. Overall, 8 different DQA1 and 19 DQB1 alleles were identified. All 21 DQA1 heterozygous combinations and 45 of 49 DQB1 heterozygous combinations were successfully resolved with TBSA. The two pairs of heterozygous DQB1 combinations that were not unambiguously typed required sequence specific PCR amplification for correct allele identification. We conclude that the method provides precise analysis for HLA-DQ typing.

DNA↗

PubMed1999

Effect of estradiol and soy phytoestrogens on choline acetyltransferase and nerve growth factor mRNAs in the frontal cortex and hippocampus of female rats.

We report here the effects of oral micronized estradiol and soy phytoestrogens on uterine weight, choline acetyltransferase (ChAT) and nerve growth factor (NGF) mRNAs in the frontal cortex and hippocampus of ovariectomized young and retired breeder rats. Within each age category, 15 bilaterally ovariectomized rats were randomized equally into three groups: control (OVX), estradiol (E2), and soy phytoestrogens (SBE). The OVX rats were fed a casein/lactalbumin-based control diet; the E2 rats were fed with the control diet with added estradiol; and the SBE rats were fed with the control diet with added soy phytoestrogens. After 8 weeks of treatment, blood, uteri, frontal cortex, and hippocampus were collected at necropsy. Results showed that the uterine weights and serum estradiol concentrations were significantly higher in the E2 group compared with those in the OVX and SBE groups. In the hippocampus of young rats, E2 treatment resulted in significantly higher NGF mRNA levels than no treatment (OVX), and NGF mRNA levels in the SBE group were intermediate between the E2 and OVX groups. ChAT mRNA levels were significantly higher in the frontal cortex of E2 and SBE-treated retired breeder rats compared to OVX retired breeder rats. There were no differences among treatment groups for ChAT mRNA levels in the frontal cortex of young rats and in the hippocampus of both young and retired breeder rats. Our data suggest that soy phytoestrogens may function as estrogen agonists in regulating ChAT and NGF mRNAs in the brain of female rats.

Age Factors↗

PubMed1999

Murine endotoxin-induced uveitis, but not immune complex-induced uveitis, is dependent on the IL-8 receptor homolog.

PURPOSE: To determine the roles of the murine interleukin-8 receptor homolog (mIL-8Rh, neutrophil chemokine CXC receptor 2) and macrophage inflammatory protein-1alpha (MIP-1alpha, a CC chemokine) in two eye inflammation models: endotoxin-induced uveitis (EIU) and immune complex-induced uveitis (reverse passive Arthus reaction (RPAR) uveitis). METHODS: For the EIU model, 250 ng E.coli endotoxin was injected into the vitreous of mIL-8Rh-/- mice or heterozygous littermate mIL-8Rh+/- controls and into MIP-1alpha-/- mice or congenic MIP-1alpha+/+ controls. Eyes were harvested after 24 h for histologic characterization of infiltrating cells and IL-6 bioassays. For the RPAR model, mouse antiserum against human serum albumin (HSA) was injected into the vitreous of mIL-8Rh-/-, mIL-8Rh+/-, MIP-1alpha-/-, and MIP-1alpha+/+ mice. Twenty-four hours later, animals were challenged with intravenous HSA. Eyes were harvested after 4 h for analysis. RESULTS: RPAR resulted in the deposition of immune complexes at the ciliary area and iris with the subsequent development of uveitis. Genetic deficiency of mIL-8Rh reduced the median number of infiltrating cells in EIU by 63% (p < 0.01) but had no effect on RPAR-induced inflammation. In the EIU model, macrophages comprised a much higher percentage (45%) of infiltrating cells in mice lacking mIL-8Rh than in controls (17%). Loss of the MIP-1alpha gene had no apparent effect on RPAR uveitis and a 39% reduction of infiltrating cells in EIU that was not statistically significant. IL-6 activity in aqueous humor was much less in mice with RPAR uveitis than in those with EIU. Neither gene deletion had a significant impact on IL-6 levels in either disease model. CONCLUSIONS: Chemokines acting via mIL-8Rh have a significant role in the induction of neutrophil infiltration during EIU but not during RPAR uveitis. MIP-1alpha is not critical for either EIU or RPAR-induced uveitis. The differential dependence on IL-8-like chemokines is in accord with the two forms ofuveitis having different etiologies and, therefore, potentially different optimal therapies.

Animals↗

PubMed1999

Cavernous hemangiomas in the cavernous sinus.

OBJECTIVE: Cavernous hemangiomas located within the cavernous sinus are rare vascular tumors that are very difficult to remove because of severe intraoperative bleeding. The purpose of this study was to analyze the clinical, neuroimaging, and pathological features and the surgical treatment of these tumors. METHODS: Ten patients with cavernous hemangiomas in the cavernous sinus who were surgically treated from August 1985 to October 1997, in our hospital, were retrospectively studied. RESULTS: Among the 10 patients, total tumor removal was performed in four cases, partial removal in two cases, and tumor biopsies in four cases. The four patients who underwent total tumor removal experienced uneventful postoperative courses, with no postoperative neurological deficits for one patient, no new neurological deficits for two patients, and complete ophthalmoplegia and diminished sensation in the distribution of Cranial Nerve V1 for one patient. The two patients who underwent partial removal developed complete ophthalmoplegia and diminished sensation in the distribution of Cranial Nerve V1 after surgery, and one of them experienced contralateral paralysis. All four patients who underwent tumor biopsies experienced severe intraoperative tumor bleeding; one exhibited Cranial Nerve III, IV, and VI injuries after surgery. CONCLUSION: The features of prominent hyperintensity in T2-weighted scans, with well-defined borders in enhancing magnetic resonance imaging scans, or marked enhancement in computed tomographic and magnetic resonance imaging scans, with no tumor blush in angiographic analyses, facilitate the diagnosis of these tumors. These tumors can be divided into two subgroups on the basis of intraoperative findings and pathological features. We do not recommend division and piecemeal removal of the tumor during surgery if the main supplies of the tumor have not been interrupted.

Adult↗

PubMed1999

Characterization of chromosomal abnormalities in prostate cancer cell lines by spectral karyotyping.

Human prostate cancer is characterized by multiple gross chromosome alterations involving several chromosome regions. However, the specific genes involved in the development of prostate tumors are still largely unknown. Here we have studied the chromosome composition of the three established prostate cancer cell lines, LNCaP, PC-3, and DU145, by spectral karyotyping (SKY). SKY analysis showed complex karyotypes for all three cell lines, with 87, 58/113, and 62 chromosomes, respectively. All cell lines were shown to carry structural alterations of chromosomes 1, 2, 4, 6, 10, 15, and 16; however, no recurrent breakpoints were detected. Compared to previously published findings on these cell lines using comparative genomic hybridization, SKY revealed several balanced translocations and pinpointed rearrangement breakpoints. The SKY analysis was validated by fluorescence in situ hybridization using chromosome-specific, as well as locus-specific, probes. Identification of chromosome alterations in these cell lines by SKY may prove to be helpful in attempts to clone the genes involved in prostate cancer tumorigenesis.

Aneuploidy↗

PubMed1999

Estimation of fetal weight: mean value from multiple formulas.

Mean fetal weight value from multiple formulas was compared to fetal weight from single formulas. Data were collected on 975 fetuses who had estimation of fetal weight by ultrasonography within 1 week before birth. Improvement in estimation of fetal weight occurred using either the mean value of multiple formulas or the Hadlock BPD/FL/AC, in comparison to fetal volume, BPD/AC, or FL/AC. BPD/FL/AC appeared to provide the best estimate of true weight in terms of overall accuracy and in terms of not showing a trend in either overestimating or underestimating true weight.

Fetal Weight↗

PubMed1999

Treatment of congenital aneurysms of the left atrium and left atrial appendage.

We report 2 cases of congenital aneurysm, 1 of the left atrium and 1 of the left atrial appendage. The patients were 14 and 27 years of age, respectively. Their common symptoms were paroxysmal palpitations and dyspnea. Diagnoses were suggested by chest radiographic films that revealed prominent convexity at the upper left border of the heart and were confirmed by echocardiography, which demonstrated a large cystic mass attached to the left atrium in each case. Aneurysmectomy was performed through a median sternotomy or a left thoracotomy, with cardiopulmonary bypass in 1 patient and without it in the other. Both patients were discharged, free of symptoms, in sinus rhythm. We conclude that echocardiography can provide a clear diagnosis and that aneurysmectomy is the treatment of choice.

Adolescent↗

PubMed1999

Distinct deleted regions on chromosome segment 16q23-24 associated with metastases in prostate cancer.

Cadherins (CDH) are cell adhesion molecules and their dysfunctions have been implicated in the development of cancer metastases. Several cadherin genes are tandemly located on 16q, which is frequently deleted in prostate cancer. We therefore used 22 markers on 16q to localize important deleted regions in metastases of this tumor. We found 16q deletions in 24/32 (75%) tumors. All lymph node and brain metastases showed extensive deletions, while 52% of primary tumors displayed limited deletions. Commonly deleted regions (CDRs) on 16q23-24, CDR2 (D16S515-D16S516) and CDR4 (D16S520-D13S3028), were strongly associated with metastases and increased Gleason score. Reduced CDH1 (E-cadherin) expression was seen in 16/32 (50%) tumors, but the CDH1 gene is not within either of these two regions. Sequencing analysis for all 16 exons of the CDH1 gene did not reveal any mutations in 10 tumors, including three brain metastases with both 16q22.1 deletion and absent E-cadherin expression. Our results implicate other, yet unidentified genes on 16q23-24 to be the frequent targets of mutations and deletions in prostate cancer metastases.

Aged↗

PubMed1999

IL-1 and TNF receptor-deficient mice show decreased inflammation in an immune complex model of uveitis.

PURPOSE: To determine the role of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in the induction of uveitis by a reverse passive Arthus reaction (RPAR). METHODS: Human serum albumin (HSA) antiserum was injected into the vitreous of "knockout" or "double knockout" mice genetically deficient in IL-1 receptor type I (IL-1RI-/-), TNF receptors p55 and p75 (TNFR p55-/-/p75-/-), IL-1RI and TNFR p55 (IL-1RI-/-/TNFR p55-/-), and controls. Twenty-four hours later, animals were challenged with intravenous HSA. Eyes were enucleated 4 hours after antigen challenge, and inflammation was quantitated by counting cells on histologic sections. Interleukin-6 in aqueous humor was measured with a B9 cell bioassay. The distribution of immune complexes in eyes was observed by immunohistochemical staining for IgG and complement component C3. RESULTS: Four hours after antigen challenge, immune complexes were localized at the ciliary body and iris of receptor-deficient mice. A transient uveitis was most severe at this time. A significant reduction in the median number of infiltrating cells was found in TNFR p55-/-/p75-/- mice (4.8, n = 15), compared with controls (14.2, n = 20, P < 0.05). The median number of infiltrating cells was significantly reduced in IL-1RI-/- mice (knockout 2.6, n = 11; controls 7.4, n = 8, P < 0.005). Interleukin-1RI-/-/TNFR p55-/- mice had a strong reduction in infiltrating cells (knockout 1.6, n = 11; controls 27.3, n = 12, P = 0.002). Interleukin-6 activity in aqueous humor was reduced in IL-1RI-/-/TNFR p55-/- mice (P = 0.03) but not in TNFR p55-/-/p75-/- (P = 0.40) mice. Most IL-1RI-/-mice had no detectable aqueous humor IL-6, but this group was not statistically different from controls. CONCLUSIONS: In contrast to endotoxin-induced uveitis, both IL-1 and TNF appear to have critical roles in RPAR uveitis. When receptors for these cytokines were deleted, the severity of immune complex-induced uveitis was profoundly reduced.

Animals↗

PubMed1999

Study on pathogenic mechanism of emotions in traditional Chinese medicine--an observation of hydrogen peroxide releasing function of celiac macrophages in rats under stress state.

The hydrogen peroxide releasing function of macrophages in rats under the stress state was observed with the animal model of "excessive anger impairing the liver". The results showed that the volume of hydrogen peroxide released from the macrophages in rats was decreased, while the corticosterone level in plasma increased after stress. It indicates that stimulation of harmful emotions could cause inhibition of immunoreaction of the organism, which might be related to the enhancement in excitability of the hypothalamus-pituitary-adrenal axis and hypersecretion of glucocorticoid hormone.

Animals↗