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Biomedical subjects

L Su

Publications and source records attributed to L Su.

At least 91 records · Page 5Linked to original sources

Identification and characterization of three genes and two pseudogenes on chromosome 13.

A study was conducted on the feasibility of isolating genes and pseudogenes that map to chromosome 13 by a hybridization-based approach using a 13-specific library and pools of repeat-free cDNA clones. Five pairs of cDNA and chromosome 13 genomic clones were identified and characterized. Partial or full-length sequence was derived from all cDNAs, and database searches were performed for putative gene identification. Partial sequence was also obtained from the chromosome 13 genomic clones for comparison with those of the hybridizing cDNAs. As a result of these analyses we identified three genes, a putative homologue of a porcine mRNA encoding an unidentified hepatic protein, a putative homologue of a yeast integral membrane protein, and a gene for a translationally controlled tumor protein, and two processed pseudogenes, ribosomal proteins L23a and S3a. The latter was formerly identified as the v-fos transformation effector gene, Fte-1, and recently cited as a possible candidate for the BRCA2 gene on chromosome 13. All genes and pseudogenes were localized to cytogenetic bands by in situ hybridization of metaphase chromosomes with probes derived from the chromosome 13 genomic clones.

Amino Acid Sequence↗

Adverse effects of medications on urinary symptoms and flow rate: a community-based study.

The relationship between urinary symptoms and medication use was investigated in a community-based cross-sectional study involving a random sample of 2115 men 40-79 years of age in Olmsted County, Minnesota. The American Urological Association Symptom Index (AUASI) was generated from a validated self-administered questionnaire. Medication use was assessed by in-person interviews. While 1087 men reported daily medication use, only 136 reported daily use of medications known to affect urinary function adversely, including antidepressants (42), antihistamines (23), and bronchodilators (43). Age-adjusted AUASI scores were higher in men reporting daily use of antidepressants, and the association persisted after additionally adjusting for the Depression and Anxiety subscales of the General Psychological Well-Being Scale (adjusted mean difference, 2.1; 95% confidence interval (CI), 0.5-3.6; p = 0.008). The adjusted AUASI was also higher among men who took antihistamines daily (adjusted mean difference, 2.3; 95% CI, 0.3-4.3; p = 0.03). Lower age-adjusted urinary flow rates occurred with antidepressants, but not with antihistamines or bronchodilators. Clinicians evaluating men for causes of voiding dysfunction in accordance with the Agency for Health Care Policy and Research practice guideline for the diagnosis and management of benign prostatic hyperplasia should be aware that daily use of antidepressants or antihistamines may be associated with AUASI scores that are two to three points higher than in men not taking these medications.

Adult↗

Expression of cytokeratin messenger RNA versus protein in the normal mammary gland and in breast cancer.

It is not known how tightly regulation of cytokeratin (CK) protein expression is correlated with transcriptional activity in breast cancer. The level of control of CK expression in the normal mammary gland and in breast cancer has been assessed by combining in situ hybridization with riboprobes, and with immunohistochemistry using monospecific antibodies. In normal mammary gland, luminal cells showed abundant hybridization with complementary RNA (cRNA) probes for CK7, CK8, CK18, and CK19. Proteins of these CKs were correspondingly distributed except for that of CK19, which showed a heterogeneous staining. In primary carcinomas, both messenger RNAs (mRNAs) and proteins of CK8 and CK18 were generally expressed to a degree similar to that of normal epithelia, but a lower level of mRNA and protein of CK18 was observed in metastatic carcinomas. Reduced expression of CK7 and CK14 was observed in all carcinomas, and the correlation between mRNA and protein for these two cytokeratins was unbalanced, whereas the expression of CK19 mRNA and the proportion of its protein-positive cells were increased. The results suggest that these major CKs in normal mammary gland epithelia are regulated at the transcriptional level except for CK19, which is partially under the posttranscriptional control. The alterations observed in breast cancer are not only reflected by the reduced or increased expression of individual cytokeratins, but characterized by partial loss of the normal regulation of cytokeratin expression.

Adult↗

Keratin 14 and 19 expression in normal, dysplastic and malignant oral epithelia. A study using in situ hybridization and immunohistochemistry.

Specific mRNA and protein for two major keratins, K14 and K19, were investigated in normal, dysplastic and malignant oral epithelia by combined in situ hybridization and immunohistochemistry. In normal epithelia, K14 mRNA and protein were present almost exclusively in the basal layer of non-cornified, and in rete-processes of cornified, sites. Dysplastic epithelium showed irregular extension of the K14 transcript and protein into superficial cells. In squamous cell carcinoma (SCC), K14 transcript was abundant in most samples whilst in one poorly differentiated carcinoma mRNA but no protein was detected. K19 mRNA and its protein were present predominantly in basal cells of noncornified epithelium, whereas in cornified epithelium only mRNA was detected. In dysplasias, K19 transcript was detected in all specimens but its protein was absent in most cases. Even more variations of K19 expression were observed in SSC. These findings indicate differences in the control of expression of K14 and K19 in normal epithelia and show that regulation is further disturbed during dysplastic change and malignancy.

Autoradiography↗

[A comparison of plasma amino acid concentrations between appropriate and small for gestational age fetuses].

OBJECTIVE: To investigate the role of amino acid played in pathogenesis of small for gestational age (SGA) fetuses. METHODS: Plasma amino acids' concentrations (PAAC) of umbilical venous samples obtained by cordocentesis before labor or at cesarean section were measured in 30 cases of appropriate for gestational age (AGA) fetuses at different gestational age. PAAC of both mother and fetuses were measured and compared in 10 cases of SGA and 10 cases of AGA. RESULTS: In cases of AGA, the PAAC in fetuses (3.11 +/- 0.41 mmol/L) were found to be higher than that in mothers. There were significant correlations between fetal and maternal PAAC. The total PAAC in mothers and fetuses, and its ratios were not changed with gestational age. In cases of SGA, essential amino acids' concentration (EAA), especially branch chain amino acid (BCAA) and lysine, decreased significantly. The feto-maternal ratios of EAA and BCAA were reduced significantly, whereas concentrations of EAA and BCAA in mothers did not change significantly. CONCLUSIONS: The results indicated that placental function and maternal nutrient supplement were important factors for maintaining fetal growth and development. In AGA cases, relationship of PAAC between mothers and fetuses were kept in a stable balance. In SGA fetuses certain amino acid metabolic disturbances existed. The reduction of some PAAC was not due to their decrease in mothers.

Amino Acids, Branched-Chain↗

[The design of air purification system and its effect on surgical ICU].

It is very important to protect air-cross infection and improve air quality in surgical intensive care unit. In the design and effect of "local air condition and purification control system", air microbe colony counter was greatly reduced to 48/m3 (control area), and 105/m3 (uncontrol area), compared to 618/m3 (untreatment), P < 0.01. This system shows stable function, sterilization effect, low cost, and is useful to protect air pollution in surgical intensive care unit.

Air Conditioning↗

[Effect of HE-NE laser acupuncture on the spleen in rats].

The splenic sinuses, lymphocytes and antigen presenting cells in the spleen of rat stimulated by He-Ne laser acupuncture were observed by using TEM to investigate the ultrastructural changes of them. The width of endothelial interstice was increased, hence a lot of blood cells oozed out of the splenic sinuses. There were numerous activated T cells which contained abundant mitochondria and ribosome in the periarterial lymphatic sheaths. The B cells were gradually differentiated into large lymphocytes, immature and mature plasmatic cells with a lot of endoplasmic reticula. They were prominently increased in the splenic nodules. The macrophages had short processes with numerous folds and microvilli and tended to neighboring lymphocytes. The nucleus pores were increased. There were a lot of vacuoles, phagosome and mitochondria were closed to macrophages and lymphocytes. In conclusion the activities of the cellular immunity and humoral immunity were enhanced by laser.

Acupuncture Points↗

Molecular structure of the halogenated anti-cancer drug iododoxorubicin complexed with d(TGTACA) and d(CGATCG).

4'-Deoxy-4'-iododoxorubicin, a halogenated anthracycline derivative, is an anticancer agent currently under Phase II clinical trials. In preclinical studies, it has demonstrated significantly reduced levels of cardiotoxicity compared to currently employed anthracyclines. It also has modified pharmacological properties resulting in an altered spectrum of experimental antitumor activity. The iodine atom at the 4' position of the sugar ring reduces the basicity and enhances the lipophilicity of this compound as compared to related anthracycline drugs. We report here single crystal X-ray diffraction studies of the complexes of 4'-deoxy-4'-iododoxorubicin with the hexanucleotide duplex sequences d(TGTACA) and d(CGATCG) at 1.6 and 1.5 A, respectively. The iodine substituent does not alter the geometry of intercalation as compared to previously solved anthracycline complexes, but appears to markedly affect the solvent environment of the structures. This could have consequences for the interaction of this drug with DNA and DNA binding proteins in cells.

Antibiotics, Antineoplastic↗

Expression of antisense osteopontin RNA inhibits tumor promoter-induced neoplastic transformation of mouse JB6 epidermal cells.

Elevated expression of osteopontin (OPN), a secreted adhesive phosphoglycoprotein, is frequently associated with many transformed cell lines of epithelial and stromal origin. Moreover, several clonal lines of preneoplastic JB6 cells derived from Balb/c mouse epidermal cultures (Colburn et al., 1978, 1979), upon treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), become irreversibly oncogenic and concomitantly synthesize OPN at elevated levels (Smith and Denhardt, 1989). In the present study we sought to determine whether OPN expression facilitates transformation of such preneoplastic (initiated) cells. We transfected TPA-promotable JB6 c141.5a cells with an expression vector containing mouse OPN cDNA in antisense orientation under transcriptional control of dexamethasone-inducible MMTV-LTR promoter. Four stably transfected clones, which expressed drastically reduced levels of OPN in the presence of both dexamethasone and TPA, were characterized. We found that (a) more than 20 copies of OPN antisense cDNA were stably incorporated into the genome of cells from two of these clones that were examined by Southern blot analysis; (b) dexamethasone-induced expression of antisense OPN RNA prevented augmented OPN expression at both mRNA and protein levels following TPA treatment; and (c) cells from all four clones failed to form colonies in soft agar medium containing both dexamethasone and TPA. Taken together, these data demonstrate that inhibition of elevated OPN expression blocks TPA-induced anchorage-independent growth of JB6 c141.5a cells, suggesting the possibility that OPN overproduction is causally related to transformation of preneoplastic cells.

Animals↗

Deletion analysis of protein kinase C inactivation by calphostin C.

Protein kinase C (PKC) undergoes specific inactivation by nanomolar concentrations of calphostin C. Both PKC-alpha (a Ca(2+)-dependent conventional isoform) and PKC-epsilon (a Ca(2+)-independent novel isoform) are similarly inactivated by calphostin C (75-100 nM produced 50% inhibition), suggesting that inactivation requires a site common to both classes of PKC. We therefore performed studies to identify a critical region in the regulatory domain of PKC-alpha required for inactivation by calphostin C. A series of N-terminal-truncation mutants of bovine PKC-alpha expressed in Saccharomyces cerevisiae was tested with 500 nM calphostin C, a concentration sufficient to inactivate wild-type PKC-alpha by 80-90%. This concentration was as effective with mutant proteins containing deletions of up to 91 amino acid (aa) residues from the amino terminus (ND91), whereas a mutant protein truncated by 140 aa (ND140) was inactivated by only 20%. These findings imply that the aa sequence 92-140 is a structural determinant of PKC-alpha inactivation by calphostin C. This sequence contains one of the phorbol ester-binding sites (aa 102-144), which is highly conserved among most PKC isoforms including PKC-epsilon. In addition to aa 92-140, PKC-stimulating cofactors (phosphatidylserine, phorbol ester, and Ca2+) are required for inactivation by calphostin C even in the case of PKC mutants that do not require these cofactors for enzymatic activity. These results suggest that cofactors provide a template that is required for productive interaction of PKC and the inhibitor. The significance of the proposed proximity effect to calphostin C action is discussed.

Animals↗

HIV-1-induced thymocyte depletion is associated with indirect cytopathogenicity and infection of progenitor cells in vivo.

Direct and indirect cytopathic mechanisms have been proposed to account for the loss of CD4+ T cells after infection with human immunodeficiency virus type 1 (HIV-1). We report here that HIV-1 infection of the human thymus in vivo results in thymocyte depletion by at least two different mechanisms. Thymocytes within multiple stages of differentiation are induced to die of apoptosis; most of these cells are uninfected. Additionally, thymopoiesis is interrupted by direct infection and destruction of intrathymic CD3-CD4+CD8- progenitor cells. These mechanisms are differentially induced by distinct isolates of HIV-1.

Animals↗

Development of a human thymic organ culture model for the study of HIV pathogenesis.

The development of effective therapies for the treatment of AIDS would be facilitated by a better understanding of HIV pathogenesis in vivo. While some aspects of pathogenesis may be assessed by standard tissue culture assays, in vivo animal models may provide clues to other aspects of HIV-mediated progression toward AIDS. Current animal models include primate models for the study of simian immunodeficiency virus (SIV) and HIV, SCID-hu and hu-PBL SCID mouse models for the study of HIV, and feline models for the study of feline immunodeficiency virus (FIV). In general these models are costly and labor intensive. We have developed a simple human fetal thymic organ culture (TOC) system that is permissive for HIV infection and that exhibits pathology similar to that observed in vivo. A key feature of this system is the time-dependent destruction of thymocytes typified by the preferential loss of CD4-expressing cells. HIV-mediated thymocyte destruction occurs by a process involving programmed cell death. We have infected TOC with a panel of HIV isolates and found that the resulting viral replicative and pathogenic profiles are similar to those seen in the SCID-hu Thy/Liv mouse, yet different from profiles observed in standard PHA-blast tissue culture assays. In addition, we find that TOC may be used to assess efficacy of antiviral agents such as AZT (3'-azido-3'-deoxythymidine) and ddI (2',3'-dideoxyinosine) in blocking both viral replication and virus-induced pathology. These results indicate that this model is amenable to the systematic manipulation, analysis, and characterization of a variety of HIV virus isolates and antiviral therapies.

Animals↗

Effects of total lymphoid irradiation on SIV-infected macaques.

The identification of antiretroviral drugs that prevent, or delay for extended periods, progression of HIV-related disease has been of limited success. Because the number of HIV-infected people continues to increase, other therapeutic approaches must be tested. Using simian immunodeficiency virus (SIV)-infected macaques in a feasibility study, total lymphoid irradiation (TLI) was administered in fractionated doses to the supradiaphragmatic and then the infradiaphragmatic lymph nodes until a cumulative dose of 34.2 Gy was achieved in each field. During treatment and for more than 1 year of follow-up, the effects of TLI on various virological, hematological, and immunological parameters were evaluated and compared to those of similarly treated, uninfected macaques. Despite sustained low numbers of CD4+ lymphocytes (< 100/microliters blood) during treatment, TLI was well tolerated, did not result in intercurrent infections, and more importantly, induced a transient decrease in viral burden and did not exacerbate disease. Remarkably, this lack of disease progression and apparent containment of SIV replication were maintained despite persistent failure of PBMCs to respond to mitogen stimulation. Because SIV (and HIV) requires activated lymphocytes to replicate, failure of PBMCs to respond fully to stimuli may have contributed to restricting virus replication. This idea was supported by in vitro experiments in which infection of PBMCs before TLI produced higher levels of cell-free SIV than those obtained during or after TLI. Last, repopulation of peripheral blood and lymph nodes with lymphocytes paralleled that observed in uninfected control animals. The results indicate that (1) immunosuppression alone is not sufficient to induce progression to AIDS, (2) SIV infection does not undermine the ability of the immune system to regenerate new cells during the clinically latent phase, and (3) further evaluation of TLI or other immunosuppressive regimens as potential therapies for HIV disease is warranted.

Animals↗

[Textual research on Newly Carved sun Zhenren's Qian jin fang].

As one of the ancient edition of Qian jin fang, this Newly Carved Sun Zhenren's Qian Jin Fang is far more authentic in the structure of its contents and its text, as compared to those editions of the Song Dynasty, and is, of course, closer to its original form and more reliable with textual significance. This article explores the distribution, characters of the edition and time of carving.

China↗

Phosducin and PP33 are in vivo targets of PKA and type 1 or 2A phosphatases, regulators of cell elongation in teleost rod inner-outer segments.

Teleost rod photoreceptors elongate in the light and shorten in darkness. We are investigating the role of cAMP-dependent protein kinase (PKA), phosphatases and target phosphoproteins in the regulation of photoreceptor cell shape. Preparations of rod fragments, consisting of the motile inner segment with attached photosensory outer segment (RIS-ROS), undergo light-stimulated elongation in culture. The PKA-selective inhibitor, H89, enhanced RIS-ROS elongation in both light and darkness, suggesting that elongation is associated with dephosphorylation of PKA substrates. Okadaic acid and calyculin A, inhibitors of type 1 and 2A phosphatases, blocked light-dependent and light-independent elongation with relative potencies suggesting that elongation requires dephosphorylation by type 1 phosphatase in light and type 2A phosphatase in darkness. To identify targets of PKA and phosphatases, RIS-ROS were isolated from retinas prelabeled with 32P-orthophosphate, and then incubated in the presence of kinase inhibitors or phosphatase inhibitors. Two phosphoproteins, PP33 and PP35, were phosphorylated by PKA and dephosphorylated by type 1 or 2A phosphatases in light- and dark-cultured RIS-ROS. PP35 (but not PP33) was immunoprecipitated by an antibody to phosducin, a PKA-regulated modulator of phototransduction (Lee et al., 1992); PP35 was also phosphorylated in vitro by a Ca2+ calmodulin-activated kinase. PP33 further differed from PP35 in its phosphopeptide maps and phosphorylation by PKC. We conclude that RIS-ROS elongation is correlated with the dephosphorylation of PKA substrates by type 1 or 2A phosphatases. Candidate mediator proteins include PP35, a fish phosducin homolog, and PP33, a newly described photoreceptor phosphoprotein.

Adaptation, Ocular↗

[Light microscope and energy dispersive X-ray analysis of amalgam pigmentation].

24 cases of amalgam pigmentation were analyzed by light microscope. 16 cases were amalgam debris, 8 cases were amalgam fragments and debris mixed. The amalgam distributed mainly along basement membrane of the epithelium, wall of blood vessels, nerve fibers, reticular fibers and endomysiums. In case where amalgam entered the bone, bone cells disappeared, lacuna emptied and microfracture of bony trabecullae occurred. In 8 cases pathologic calcification were found and in 18 cases there were inflammatory responses. 2 cases were analyzed by energy dispersive X-ray. It was found that in the different sites of tissues there were different content of Ag, Hg, Sn and Ca.

Adolescent↗