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Biomedical subjects

Y Cao

Publications and source records attributed to Y Cao.

At least 199 records · Page 11Linked to original sources
PubMed1999

A newly identified, essential catalytic residue in a critical secondary structure element in the integrase family of site-specific recombinases is conserved in a similar element in eucaryotic type IB topoisomerases.

The integrase family of site-specific recombinases catalyzes conservative rearrangements between defined segments of DNA. A highly conserved tetrad (RHRY) of catalytic residues is essential for this process. This tetrad is dispersed in two motifs in the linear sequence, but is configured appropriately in the catalytic pocket to execute the strand cleavage and rejoining reactions. A third conserved motif has been identified in the Xer subgroup of the integrase family. Mutational analysis of 12 conserved residues in this motif in the XerD protein from Salmonella typhimurium led to the identification of an essential fifth catalytic residue (lysine 172) which is implicated in strand cleavage or exchange. This lysine residue occupies part of the turn of an antiparallel beta-hairpin which forms one side of the catalytic cleft in XerD, and is found at similar positions among evolutionarily diverse integrase family members. Related antiparallel beta-hairpins are present in eucaryotic type IB topoisomerase enzymes which also contain a critical lysine residue in the turn of the hairpin. In both the integrase family and eucaryotic type IB topoisomerases, the catalytic lysine residues are in close contact with the substrates and may play similar roles in influencing the reactivity of the phosphotyrosine intermediates formed during reactions catalyzed by both enzymes.

Amino Acid Sequence↗
PubMed1999

The nucleosome remodeling complex, Snf/Swi, is required for the maintenance of transcription in vivo and is partially redundant with the histone acetyltransferase, Gcn5.

Snf/Swi, a nucleosome remodeling complex, is important for overcoming nucleosome-mediated repression of transcription in Saccharomyces cerevisiae. We have addressed the mechanism by which Snf/Swi controls transcription in vivo of an Snf/Swi-dependent promoter, that of the SUC2 gene. By single-cell analysis, our results show that Snf/Swi is required for activated levels of SUC2 expression in every cell of a population. In addition, Snf/Swi is required for maintenance of SUC2 transcription, suggesting that continuous chromatin remodeling is necessary to maintain an active transcriptional state. Finally, Snf/Swi and Gcn5, a histone acetyltransferase, have partially redundant roles in the control of SUC2 transcription, suggesting a functional overlap between two different mechanisms believed to overcome repression by nucleosomes, nucleosome remodeling and histone acetylation.

Acetyltransferases↗
PubMed1999

Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis.

Proteolytic enzymes are involved in generation of a number of endogenous angiogenesis inhibitors. Previously, we reported that angiostatin, a potent angiogenesis inhibitor, is a proteolytic fragment containing the first four kringle modules of plasminogen. In this report, we demonstrate that urokinase-activated plasmin can process plasminogen to release an angiogenesis inhibitor, K1-5 (protease-activated kringles 1-5). K1-5 inhibits endothelial-cell proliferation with a half-maximal concentration of approximately 50 pM. This inhibitory effect is endothelial-cell-specific and appears to be at least approximately 50-fold greater than that of angiostatin. A synergistic efficacy of endothelial inhibition was observed when angiostatin and kringle 5 (K5) were coincubated with capillary endothelial cells. The synergistic effect is comparable to that produced by K1-5 alone. Systemic treatment of mice with K1-5 at a low dose significantly blocked the fibroblast growth factor-induced corneal neovascularization, whereas angiostatin had no effect at the same dose. K1-5 also suppressed angiogenesis in chicken embryos. Systemic administration of K1-5 at a low dose at which angiostatin was ineffective significantly suppressed the growth of a murine T241 fibrosarcoma in mice. The antitumor effect correlates with the reduced neovascularization. These findings suggest that the plasmin-mediated proteolysis may be involved in the negative switch of angiogenesis.

Angiostatins↗
PubMed1999

Systemic gene delivery expands the repertoire of effective antiangiogenic agents.

Cationic liposome-DNA complex (CLDC)-based intravenous gene delivery targets gene expression to vascular endothelial cells, macrophages and tumor cells. We used systemic gene delivery to identify anti-angiogenic gene products effective against metastatic spread in tumor-bearing mice. Specifically, CLDC-based intravenous delivery of the p53 and GM-CSF genes were each as effective as the potent antiangiogenic gene, angiostatin, in reducing both tumor metastasis and tumor angiogenesis. Combined delivery of these genes did not increase anti-tumor activity, further suggesting that each gene appeared to produce its antimetastatic activity through a common antiangiogenic pathway. CLDC-based intravenous delivery of the human wild type p53 gene transfected up to 80% of tumor cells metastatic to lung. Furthermore, it specifically induced the expression of the potent antiangiogenic gene, thrombospondin-1, indicating that p53 gene delivery in vivo may inhibit angiogenesis by inducing endogenous thrombospondin-1 expression. CLDC-based delivery also identified a novel anti-tumor activity for the metastasis suppressor gene CC3. Thus, CLDC-based intravenous gene delivery can produce systemic antiangiogenic gene therapy using a variety of different genes and may be used to assess potential synergy of combined anti-tumor gene delivery and to identify novel activities for existing anti-tumor genes.

Angiostatins↗
PubMed1999

Magnetic resonance imaging of perfusion in rat cerebral 9L tumor after nicotinamide administration.

PURPOSE: To investigate the effect of nicotinamide on normal brain and 9L tumor blood flow in the rat using magnetic resonance imaging (MRI) and arterial spin tagging. METHODS AND MATERIALS: Using MRI at 7 Tesla, measurements of blood perfusion were determined from two-dimensional maps of intracerebral 9L rat tumors and normal Fischer rat brains. The spatial and temporal influence of nicotinamide, 500 mg/kg i.p., on cerebral blood flow (CBF) was studied in normal brain and tumors between 5 and 21 days after tumor implantation. The MRI CBF measurements employed a variable tip-angle-gradient-recalled echo (VTA-GRE-CBF) readout of the magnetization of the tissue slice. The VTA-GRE-CBF required 8 minutes for a blood flow image with inplane resolution of 250 microm x 500 microm x 2 mm. RESULTS: Normal brain blood flow decreased following the administration of nicotinamide. In contrast, tumor blood flow remained unaffected in the time following nicotinamide administration. Consequently, the blood flowing in the tumor relative to that in normal brain demonstrated a significant and selective increase in response to nicotinamide administration. Relative tumor blood flow increased at 10 minutes after nicotinamide injection compared with predrug levels and remained elevated for at least 1 hour. CONCLUSION: The results suggest that nicotinamide will not enhance radiosensitivity of brain tumors. The results support the use of nicotinamide to improve delivery of anticancer therapeutics through its ability to selectively increase tumor blood flow relative to that in normal brain.

Animals↗
PubMed1999

Anatomical and neurochemical peculiarities of the pika retina: basis for lack of circadian rhythm of core temperature.

We have previously reported a complete lack of circadian rhythm in the body temperature of pikas in contrast to other lagomorphs. In this present study, the anatomical and neurochemical findings by immunohistochemical, photo and electron microscopic methods reveal that the photoreceptor system of this animal is poorly developed. This probably explains their stable core body temperature which help them survive in cold temperatures.

Animals↗
PubMed1999

Functional MRI-BOLD of visually triggered headache in patients with migraine.

BACKGROUND: Spreading depression of Leao has been hypothesized as the basis for the visual aura of the migraine attack, supported by cerebral blood flow measurements of spreading hypoperfusion. The early depolarizing or activation phase of experimental spreading depression, however, is associated with a transient but pronounced cerebral blood flow increase that precedes spreading hypoperfusion. OBJECTIVE: To study this early phase of the migraine attack, we investigated visually triggered attacks of headache and visual symptoms using a red-green checkerboard stimulus in patients with migraine. INTERVENTIONS: We studied occipital cortex activation during visual stimulation by measuring occipital cortex perfusion with functional magnetic resonance imaging-blood oxygenation level-dependent contrast in 10 patients with migraine with aura and 2 patients with migraine without aura and 6 healthy subjects. RESULTS: In 6 patients with migraine with aura and 2 patients with migraine without aura, their typical headache with (n = 2) or without visual change was visually triggered at 7.3 minutes (mean time) after visual stimulation began. In 5 of these patients, the onset of headache or visual change, or both, was preceded by suppression of initial activation (mean onset time, 4.3 minutes; P<.001) The suppression slowly propagated into contiguous occipital cortex at a rate ranging from 3 to 6 mm/ min. This neuronal suppression was accompanied by baseline contrast intensity increases that indicated vasodilatation and tissue hyperoxygenation. CONCLUSIONS: We conclude that visually triggered headache and visual change in patients with migraine is accompanied by spreading suppression of initial neuronal activation and increased occipital cortex oxygenation. We postulate that this spreading suppression may be associated with initial activation of a migraine attack, independent of whether there are associated aura symptoms. We further postulate that there may be an association between vasodilation accompanying the initial stage of suppression and the induction of headache.

Adult↗
PubMed1999

Rapid colorimetric assay of urinary beta-galactosidase and N-acetyl-beta-D-glucosaminidase with Cobas Mire Auto-analyzer.

A rapid and simple colorimetric method for the assay of urinary beta-galactosidase (GAL) and N-acetyl-beta-D-glucosaminidase (NAG) using 4-nitrophenyl-glycosides as the substrates and a Cobas Mire Auto-analyzer is described. Optimal conditions for this method including substrate concentration, ionic strength, pH and incubation time were characterized. Endogenous substances in urine did not interfere with the assays. Incubation time could be shortened to 10 minutes. A small volume of an alkaline buffer to terminate the enzyme reaction achieved better sensitivity and accuracy. Buffer-substrate solutions were stable for at least one week at 4 degrees C. Normal values of the two urinary enzymes are also reported.

Acetylglucosaminidase↗
PubMed1999

Anti-Yo positive paraneoplastic cerebellar degeneration associated with ovarian carcinoma: case report and review of the literature.

Paraneoplastic cerebellar degeneration (PCD) is a rare nonmetastatic neurological complication in cancer patients. Anti-Yo is one of the anti-onconeural antibodies found in PCD patients. It is believed that anti-Yo occurs almost always in women and is most likely associated with gynecologic or breast cancers, although exceptions exist. Here we report a PCD patient with ovarian cancer having high-titer anti-Yo. The acute onset of her PCD symptoms mimicked that of a stroke. Her ovarian cancer tissue contained abundant plasma cells and lymphocytes. After a thorough review of the literature, we propose a schematic hypothesis for the autoimmune pathogenesis of PCD. Despite anecdotal case reports of neurological improvement with different combinations of treatment, including IVIg, there is still no definitely effective treatment for PCD. Further research on the pathogenesis of PCD may lead to more effective therapies.

Aged↗
PubMed1999

Glutamine protects against doxorubicin-induced cardiotoxicity.

UNLABELLED: Doxorubicin (DOX) dose-intensive therapy for breast cancer is limited by a cardiomyopathy that often results in overt congestive heart failure. We hypothesized that dietary glutamine (GLN) can diminish DOX-induced cardiotoxicity by maintaining tissue glutathione (GSH) levels and thus preventing the proposed mechanism of cardiac injury: oxidation. METHODS: Forty-two female Fisher 344 rats were randomized into one of six groups: GLN + saline (SAL), GLN + DOX, freamine (FA) + SAL, FA + DOX, H2O + SAL, and H2O + DOX. Rats were pair-fed chow and gavaged with 1 g/kg/day GLN or an isonitrogenous amount of FA or H2O for 28 days. Rats were injected intravenously with a single dose of SAL or 9 mg/kg DOX on day 7 of gavage. At 28 days (21 days post-DOX), rats were sacrificed and blood and cardiac tissue were assayed for GLN and GSH content and lipid peroxidation (LP). RESULTS: There were no differences in cardiac GSH levels and cardiac lipid peroxidation in GLN + SAL versus GLN + DOX groups. However, blood and cardiac GSH levels were significantly decreased in H2O + DOX and FA + DOX groups compared to controls (H2O + SAL and FA + SAL). CONCLUSION: These data suggest that dietary GLN supplementation may diminish DOX-induced oxidative damage and thus cardiotoxicity through upregulation of cardiac GSH metabolism.

Animals↗
PubMed1999

Histochemical observation of nitric oxide synthase in trigeminal ganglion of rats with experimental pulpitis.

In order to understand the roles of nitric oxide (NO) in pulpalgia and pulpitis, the histochemistry of nitric oxide synthase (NOS) in the neurons of trigeminal ganglion in experimental pulpitis rat and human inflammatory dental pulp tissues were histochemically studied by NADPH-diaphorase (NADPH-D) techniques. Results showed that NADPH-D positive neurons were scattered in rat trigeminal ganglions, but the sizes of positive neurons were not changed. None of NOS-positive fibers was found in human normal and inflammatory dental pulp tissues. The results suggested that NOS in trigeminal ganglion might play an important role in sensory transmission and regulation of pulpalgia. The absence of NOS-positive nerves in human pulp suggested that NO may not be related to inflammatory stimulation and transmission in dental pulp tissues.

Animals↗
PubMed1999

Lung cancer and the human gene for ribonucleotide reductase subunit M1 (RRM1).

LOH11A is a region of Chromosome (Chr) 11p15.5 where 75% of lung cancers show loss of heterozygosity (LOH). Clinical and cell biological studies suggest that LOH11A contains a tumor/metastasis suppressor gene. We have mapped this region (650 kb) using overlapping genomic P1/PAC/BAC clones, and one of the genes that we have identified is RRM1. This gene encodes the large subunit (M1) of ribonucleotide reductase, the heterodimeric enzyme that catalyzes the rate-limiting step in deoxyribonucleotide synthesis. By comparing our genomic sequences with the previously published cDNA, we have found that the human gene is composed of 19 exons. It is oriented telomere to centromere and is Alu rich. In order to verify that RRM1 maps within the boundaries of LOH11A, we assessed the frequency of LOH at a SacI polymorphism within intron IX of the gene. We observed LOH in 48% (15/31) of informative lung tumor specimens. To determine whether RRM1 was mutated in tumors, SSCP analysis of the 19 RRM1 exons was performed. No mutations were revealed in 12 pairs of normal and tumor DNA samples. Immunoblots on protein extracts from normal/tumor pairs indicated that a protein of the expected size was present in both. Our conclusion is that RRM1 lies within the LOH11A region, but that its exons are not mutated in tumors. The potential for RRM1 to act as a tumor suppressor is discussed.

Base Sequence↗
PubMed1999

TGF-beta1 mediates 70-kDa heat shock protein induction due to ultraviolet irradiation in human skin fibroblasts.

Ultraviolet B (UVB) alters the expression of heat shock protein 70 (HSP70) in cultured fibroblast cells derived from human skin. However, the nature of the signal transduction pathway remains to be determined. Transforming growth factor-beta (TGF-beta) has a large variety of biological functions, including cell growth control, modulation of inflammation and immunoregulation. In this study, we examined whether TGF-beta is associated with the process of HSP70 expression induced by UVB irradiation. The constitutive expression of TGF-beta1 mRNA and HSP70 expression in human skin fibroblast cells were detected using reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The results indicate that: (1) UVB irradiation stimulates HSP70 expression in a dose- and time-dependent manner, (2) constitutive expression of TGF-beta1 mRNA is detected after UVB irradiation, the level of which peaks at 4 h after 10 mJ cm-2 of UVB irradiation, (3) HSP70 expression is induced by TGF-beta1 without UVB irradiation, and (4) HSP70 expression induction with UVB irradiation is inhibited by preincubation of the cells with the anti-TGF-beta type II receptor antibody. Our results suggest that HSP70 expression induced by UVB involves the autocrine signalling of TGF-beta production.

Blotting, Western↗
PubMed1999

Expression of MUC1, Thomsen-Friedenreich antigen, Tn, sialosyl-Tn, and alpha2,6-linked sialic acid in hepatocellular carcinomas and preneoplastic hepatocellular lesions.

The expression of epithelial mucins and Thomsen-Friedenreich-related antigens in preneoplastic and neoplastic hepatocellular lesions was systematically investigated using an in situ immunohistochemical staining approach. MUC1, MUC2, TF, sialosyl-TF, Tn, sialosyl-Tn, alpha2,3-linked sialic acid, and alpha2,6-linked sialic acid were examined in normal and cirrhotic human liver and in human hepatocellular carcinomas (HCCs) and cholangiocarcinomas. Normal hepatocytes and preneoplastic foci of altered hepatocytes did not express MUC1, MUC2, TF, Tn, s-Tn, or alpha2,6-linked sialic acid. In contrast, HCCs showed positive reactions for MUC1, TF, Tn, s-Tn, and alpha2,6-linked sialic acid. MUC2 was absent in normal biliary epithelial cells, but present in cholangiocarcinomas. The staining of MUC1, or s-Tn and alpha2,6-linked sialic acid in human normal liver tissues and various liver diseases did not change after specific treatments such as periodate oxidation or saponification, indicating that their expression in HCC does not result from incomplete glycosylation or low O-acetylation, respectively. MUC1, TF, Tn, s-Tn, and alpha2,6-linked sialic acid may be useful as indicators of progression of HCC in tissue sections, and perhaps also as targets for diagnostic and therapeutic approaches in vivo.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1999

Molecular tracking of an Human Immunodeficiency Virus nef specific cytotoxic T-cell clone shows persistence of clone-specific T-cell receptor DNA but not mRNA following early combination antiretroviral therapy.

The mechanisms that lead to maintenance of an active effector cytotoxic T-cell (CTL) response in Human Immunodeficiency Virus type-1 (HIV-1) infection are not well understood. We have investigated the role of antigen in maintenance of an HIV-1 specific CTL response by studying a patient (313-7) whose antigenic stimulus was reduced using antiretroviral drug therapy started within 90 days of HIV-1 infection. This patient made a primary monospecific CTL response to an HLA-C*0802 restricted epitope in nef (KAAVDLSHFL) prior to treatment. Within 7 days of starting treatment the nef specific CTL precursor frequency (CTLp) had decreased from 60/10(6) to 4/10(6) peripheral blood mononuclear cells (PBMC), coincident with a decline in viremia from 18 470 to 615 copies/ml. Both plasma viremia and nef specific CTLp remained at low levels for 180 days. The nef-specific CTL clone T-cell receptor (TCR) mRNA transcripts also decreased after treatment, but clone specific TCR DNA persisted. It appears that removal of antigen alters the state of HIV specific CTL from an activated effector population (detected in the CTLp assay and by measurement of clone specific RNA) to a non-activated quiescent population (detected by measurement of clone-specific DNA). This latter population may represent persisting HIV specific memory CTL.

Adult↗
PubMed1999

Gene structure and amino acid sequence of Latimeria chalumnae (coelacanth) myelin DM20: phylogenetic relation of the fish.

The structure of Latimeria chalumnae (coelacanth) proteolipid protein/DM20 gene excluding exon 1 was determined, and the amino acid sequence of Latimeria DM20 corresponding to exons 2-7 was deduced. The nucleotide sequence of exon 3 suggests that only DM20 isoform is expressed in Latimeria. The structure of proteolipid protein/DM20 gene is well preserved among human, dog, mouse, and Latimeria. Southern blot analysis indicates that Latimeria DM20 gene is a single-copy gene. When the amino acid sequences of DM20 were compared among various species, Latimeria was more similar to tetrapods than other fishes including lungfish, confirming the previous finding by immunoreactivity (Waehneldt and Malotka 1989 J. Neurochem. 52:1941-1943). However, when phylogenetic trees were constructed from the DM20 sequences, lungfish was clearly the closest to tetrapods. Latimeria was situated outside of lungfish by the maximum likelihood method. The apparent similarity of Latimeria DM20 to tetrapod proteolipid protein/DM20 is explained by the slow amino acid substitution rate of Latimeria DM20.

Amino Acid Sequence↗