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Biomedical subjects

S Lu

Publications and source records attributed to S Lu.

At least 271 records · Page 15Linked to original sources

[Color Doppler echocardiography in the diagnosis for ruptured aneurysm of sinus of Valsalva].

Twenty-five cases with ruptured aneurysm of sinus of Valsava were detected by color Doppler sonography and twenty-four cases undenwent surgical repair. In twenty-three cases, the sonographic findings of the site of the aneurysm and the chambers into which aneurysm ruptured were coincident with the surgical findings. The accuracy was 95.8%. The size of the aneurysm and the diameter of the ruptured site detected by ultrasound were correlated well with surgical findings. The associated lesions obtained by ultrasound were completely identical with surgical findings. Color Doppler flowing imaging has special value in diagnosing the ruptured aneurysm of sinus of Valsalva.

Adolescent↗

Activated N-ras oncogene and N-ras proto-oncogene act through the same pathway for in vivo tumorigenesis.

We compared the tumorigenic effects of the N-ras oncogene and the N-ras proto-oncogene in lymphoid and mammary tissues in an in vivo model. For this purpose, we generated transgenic mice with high levels of N-ras oncogene or N-ras proto-oncogene expression, driven by the complete mouse mammary tumor virus LTR (MMTV-LTR) (MMTV/N-rasT and MMTV/N-rasN constructs) and transgenic mice with low levels of N-ras oncogene or N-ras proto-oncogene expression, driven by a truncated MMTV-LTR (TMTV/N-rasT and TMTV/N-rasN constructs). We show that both, the N-ras proto-oncogene and the N-ras oncogene with a C:G-->A:T mutation at codon 61, lead to identical tumor types: lymphoblastic T-cell lymphomas, cleaved B-cell lymphomas and poorly differentiated mammary carcinomas. Nevertheless, there were quantitative differences in tumor incidence and latency and in transgene expression among N-ras oncogene and N-ras proto-oncogene transgenics. Despite these differences in tumor kinetics, the predisposition to identical tumor types is in agreement with the idea that the N-ras oncogene and the N-ras proto-oncogene act through the same pathway for in vivo tumorigenesis in B-cells, T-cells or mammary epithelial cells.

Animals↗

Synthesis and characterization of pseudopeptide bradykinin B2 receptor antagonists containing the 1,3,8-triazaspiro[4.5]decan-4-one ring system.

A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl-substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids as amino acid surrogates to replace the Pro2-Pro3-Gly4-Phe5 section of the peptide bradykinin B2 receptor antagonist [Pro3, Phe5]HOE 140 (D-Arg0-Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-D-Tic7+ ++-Oic8-Arg9) were prepared. These psuedopeptides were examined in vitro for their B2 receptor affinities as well as for their ability to block bradykinin mediated actions in vivo. Two compounds in particular, NPC 18521 (I) and NPC 18688 (V) were quite potent in these latter assays, indicating that a significant portion of this prototypical second generation decapeptide antagonist can be replaced with a more compact nonpeptide molecule.

Amino Acid Sequence↗

DNA vaccines.

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Animals↗

Effects of intraaortic balloon pumping on septal arterial blood flow velocity waveform during severe left main coronary artery stenosis.

OBJECTIVES: We sought to evaluate the effect of intraaortic balloon pumping on the phasic blood velocity waveform into myocardium with severe coronary artery stenosis. BACKGROUND: In the presence of severe coronary artery stenosis, it is not clear whether intraaortic balloon pumping augments intramyocardial inflow during diastole or changes systolic retrograde blood flow from the myocardium to the extramural coronary arteries. METHODS: Using anesthetized open chest dogs (n=7), we introduced severe stenosis in the left main coronary artery to reduce the poststenotic pressure to approximately 60 mm Hg (>90% diameter stenosis). Septal arterial blood flow velocities were measured with a 20-MHz, 80-channel ultrasound pulsed Doppler velocimeter. Left anterior descending arterial flow, aortic pressure and poststenotic distal coronary pressure were measured simultaneously. The diastolic anterograde flow integral and systolic retrograde flow integral were compared in the presence and absence of intraaortic balloon pumping. RESULTS: Although intraaortic balloon pumping augmented diastolic aortic pressure, this pressure increase was not effectively transmitted through stenosis. Septal arterial diastolic flow velocity was not augmented, and left anterior descending arterial flow was unchanged during intraaortic balloon pumping. CONCLUSIONS: In the presence of severe coronary artery stenosis, intraaortic balloon pumping failed to increase diastolic inflow in the myocardium and did not enhance systolic retrograde flow from the myocardium to the extramural coronary artery. Thus, the major effect of intraaortic balloon pumping on the ischemic heart with severe coronary artery stenosis may be achieved by reducing oxygen demand by systolic unloading.

Analysis of Variance↗

Identification and characterization of a versatile retinoid response element (retinoic acid receptor response element-retinoid X receptor response element) in the mouse tissue transglutaminase gene promoter.

Tissue transglutaminase (transglutaminase type II) is an intracellular protein cross-linking enzyme that accumulates in connective tissue and in cells undergoing apoptosis. Retinoids regulate the transcription of the mouse tissue transglutaminase gene via activation of regulatory elements contained within 4 kilobases of the 5'-end of the gene. Co-transfection studies with retinoid receptor expression vectors in CV-1 cells demonstrated that the mouse tissue transglutaminase promoter is activated by ligand activation of either retinoic acid receptor-retinoid X receptor (RAR.RXR) heterodimers or RXR homodimers. Optimal induction is achieved with retinoid receptor panagonists; partial activation can also be achieved with either RAR-specific or RXR-specific retinoids. Retinoid-dependent activation of the tissue transglutaminase promoter depends on both a proximal regulatory region containing sequences highly conserved between the human and the mouse tissue transglutaminase promoters and a distal region that includes a 30-base pair retinoid response element (mTGRRE1). mTGRRE1 contains three hexanucleotide half-sites (two canonical and one non-canonical) in a DR7/DR5 motif that bind both RAR*RXR heterodimers and RXR homodimers. These studies suggest that retinoid-dependent expression of the mouse tissue transglutaminase gene is mediated by a versatile tripartite retinoid response element located 1.7 kilobases upstream of the transcription start site.

3T3 Cells↗

Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats.

To investigate whether a BP-regulatory locus exists in the vicinity of the renin locus on rat chromosome 13, we transferred this chromosome segment from the Dahl salt-sensitive (S) rat onto the genetic background of the Dahl salt-resistant (R) rat. In congenic Dahl R rats carrying the S renin gene and fed an 8% salt diet, systolic BP was significantly lower than in progenitor Dahl R rats: 127 +/- 1 mmHg versus 138 +/- 4 mmHg, respectively (P < 0.05). Moreover, the decreased BP in the congenic Dahl R strain was associated with decreased kidney renin mRNA and decreased plasma renin concentration. These findings demonstrate that the Dahl S strain carries alleles in or near the renin locus that confer lower plasma renin concentration and lower BP than the corresponding alleles in the Dahl R strain, at least when studied on the genetic background of the Dahl R rat and in the environment of a high salt diet. The occurrence of coincident reductions in kidney renin mRNA, plasma renin concentration, and BP after interstrain transfer of naturally occurring renin gene variants strongly suggests that genetically determined variation in renin gene expression can affect BP.

Alleles↗

Known HPV types have no association with keratoacanthomas.

Certain HPV types have been linked to the genesis and development of premalignant and malignant skin diseases. There have been several contradictory reports on the role of HPV infections in the development of keratoacanthomas (KAs). To further study the involvement of HPVs in the aetiology of KAs, we investigated paraffin-embedded specimens of 80 biopsies of KAs for the presence of HPV 1, 2, 3, 4, 5, 7, 26, 37, 38, 47 and 59 DNA by in situ hybridization (ISH) with biotinylated probes under high stringency conditions (Tm-10 degrees C). Every fourth biopsy specimens was also examined by polymerase chain reaction (PCR) with consensus primers targeting the HPV E1 and L1 regions. The positive cases were further studied by direct DNA sequencing. All specimens proved to be negative for all HPV DNAs studied by ISH. Three out of 20 cases produced in positive PCR amplifications when consensus primers targeting the L1 region were used. However, the same samples remained negative with general primers targeting the E1 region. The DNA sequence analysis of the PCR-positive products showed a 76% homology with HPV type 17. Our results suggest that the known HPV types are unlikely to have any role in the aetiology of KAs.

Base Sequence↗

Expression of PCNA is associated with the presence of HPV DNA in skin warts.

A series of 90 excised cutaneous warts (verrucae vulgaris) were studied for the presence of HPV (human papillomavirus) DNA using in situ hybridization (ISH) with biotinylated full genomic DNA probes of HPV types 1, 2, 3, and 4. The expression of PCNA (proliferating cell nuclear antigen) was examined using conventional immunohistochemistry. The aim was to test the hypothesis that HPV can reactivate PCNA, including in the host replication machinery. HPV DNA of the above types was detected in 60 of 90 verruca biopsies studied (66.7%): HPV 2 in 56 cases, HPV 1 in 2 cases, and HPV 3 in 2 cases. PCNA was expressed in all samples except two. The signal distribution of HPV DNA markedly differed from that of PCNA expression. ISH revealed strong HPV DNA signals in both the granular and the upper spinous cell layers, the most intense signals being detected in the upper epidermis. On the other hand, nuclear PCNA staining was present in the majority of parabasal and basal cells. Although strong PCNA signals within the wart lesions were found in the areas where HPV DNA was present, the PCNA positivity was almost invariably localized in the differentiated cells of the spinous cell layers, just below the HPV DNA-expressing cells. At the margins of the lesions, PCNA expression was still strong but disappeared abruptly towards the normal epidermis. HPV DNA-positive warts showed more intense expression of PCNA than did the HPV DNA-negative ones in this study. Our results indicate that PCNA induction is associated with the presence of HPV DNA, suggesting that HPV can reactivate PCNA, thus interfering with the host cell DNA replication machinery.

Cell Differentiation↗

Failure to demonstrate human papillomavirus (HPV) involvement in Bowen's disease of the skin.

To assess the role of human papillomavirus (HPV) in the aetiology of extragenital Bowen's disease (EBD), a series of 91 cases were analysed using in situ hybridization (ISH) with whole genomic DNA probes of HPV types 1, 2, 4, 6, 7, 11, 12, 15, 16, 18, 26, 36, 37, 39, 42, 55 and 59. No HPV DNA was found in any of the samples tested. A polymerase chain reaction (PCR) was also used to analyse 37 of the 91 samples, using both the consensus primers MY09/MY11 which amplify a large number of HPV types from the L1 region and the degenerate primers CP65/CP70, which amplify the complete set of epidermodysplasia verruciformis (EV) HPV types. All the cases were also negative in the PCR. The results suggest that EBD is not HPV-related, at least in immunocompetent patients.

Aged↗

Paralytic shellfish poisoning in southern China.

The rapidly expanding mariculture and commercial region along the southern coast of China has experienced sporadic outbreaks of paralytic shellfish poisoning for nearly 30 years, yet virtually nothing is known of the nature of that toxicity or of the causative organisms. This study presents the first direct comparisons of the high performance liquid chromatography toxin composition profiles of shellfish implicated in paralytic shellfish poisoning outbreaks in Daya Bay with Alexandrium tamarense cultures established from those waters. The three cultures that were analyzed produced an unusually high proportion of the low potency N-sulfocarbamoyl toxins C1 and C2 (nearly 90% of the total), and only trace quantities of the other saxitoxin derivatives. Total toxicity was thus very low with mild acid extraction, ranging between 7.2 and 12.7 fmole cell-1, or 0.7-0.9 pg saxitoxin equiv. cell-1. Following acid hydrolysis using the standard AOAC extraction method, the dominant toxins in the cultures were gonyautoxins 2 and 3 and decarbamoyl gonyautoxins 2 and 3. Total potency increased fourfold to 2.6-3.4 pg saxitoxin equiv. cell-1 following acid hydrolysis. These cultures are thus at the low end of the range of toxicities recorded for members of the A. tamarense species complex. Two scallop samples and one mussel sample collected from Daya Bay during paralytic shellfish poisoning episodes in 1990 and 1991 were also analyzed following the AOAC extraction procedure. The toxin profiles were similar for the three shellfish samples, in that the same suite of toxins were present in each, but the relative proportion of those toxins varied. The dominant toxins were gonyautoxins 2 and 3 and toxins C1-C4. Total toxicity was 336 and 654 micrograms saxitoxin per 100 g meat for the scallop samples, and 723 for the mussels. Toxins C3,4 were present in the shellfish at up to 22 mole%, but were not detected in cultures, even when mild acid was used for extraction. Despite the otherwise similar nature of the culture versus the shellfish toxin signatures, the presence of C3,4 indicates that another strain or species of Alexandrium, or possibly a paralytic shellfish poisoning-producing species of another genus was responsible for the 1990 and 1991 paralytic shellfish poisoning outbreaks in Daya Bay. Since the cultures analyzed were of low intrinsic toxicity, A. tamarense may be more widespread along the south coast of China than is suggested by the sporadic pattern of past paralytic shellfish poisoning outbreaks. Blooms with high cell density are required to generate sufficient toxin to be dangerous. The alarming increase in algal blooms in Chinese waters due to persistent and growing pollution may make these low toxicity populations more problematic in the future.

Animals↗

Separate cis-acting elements determine the expression of mouse Dbx gene in multiple spatial domains of the central nervous system.

Dbx, a divergent homeobox gene, is expressed in a regionally restricted pattern in the developing mouse central nervous system (CNS). In order to understand its spatial regulation, we have isolated a cis-regulatory region using a reporter gene analytical approach in transgenic mice. A 5.7 kb DNA fragment that contains the transcriptional start site of the Dbx gene is sufficient to direct the expression of the transgene to various domains of the CNS in a temporally regulated fashion. The transgene expression can be detected between 9.5 and 15.5 days post coitum in embryos in the fore-, mid- and hindbrain and spinal cord in regions where the endogenous gene is expressed. Additionally, transgene expression can also be detected in the oculomotor nerve (cranial nerve III). The expression of the transgene closely resembles that of the Dbx gene with minor, but interesting differences. These results suggest that major cis-acting elements reside within a 5.7 kb DNA fragment located 5' of the Dbx gene. Further deletion analysis shows that at least two independently regulated elements are present within this DNA fragment: an element that directs expression to the brain and spinal cord and a second element that directs expression to the oculomotor nerve.

Amino Acid Sequence↗

Transport properties are not altered across Caco-2 cells with heightened TEER despite underlying physiological and ultrastructural changes.

Selected properties of Caco-2 cells were examined after disparate transepithelial electrical resistance (TEER) measurements were observed in two populations of Caco-2 cells. Comparisons were made between the early passages of Caco-2 cells (Caco-2E, passages 35-47) and the later passages of cells (Caco-2L, passages 87-112). Transmission electron microscopy revealed that regions of Caco-2L cells were composed of multiple cell layers rather than the monolayers observed in Caco-2E cells. Epithelial cell height (or barrier thickness) was not significantly different between the two cell populations. Intercellular and intracellular lumina were observed in the Caco-2L cells, but not in the Caco-2E cells. Results of [3H]thymidine incorporation assays showed significantly higher cell proliferation rates in Caco-2L cells relative to Caco-2E cells. Despite morphological and physiological changes, there were no significant differences in the apparent permeabilities for D-mannitol (paracellular diffusion marker), hydrocortisone (transcellular diffusion marker), or dipeptide, Gly-Sar (carrier-mediated transcellular transport marker) between the two populations of cells. The higher TEER values in Caco-2L cells may be the results of a slight perturbation of tight junctions associated with both the multiple cell layers and the presence of intercellular lumina.

Caco-2 Cells↗

Exchange of precursor-specific elements between Pro-sigma E and Pro-sigma K of Bacillus subtilis.

sigma E and sigma K are sporulation-specific sigma factors of Bacillus subtilis that are synthesized as inactive proproteins. Pro-sigma E and pro-sigma K are activated by the removal of 27 and 20 amino acids, respectively, from their amino termini. To explore the properties of the precursor-specific sequences, we exchanged the coding elements for these domains in the sigma E and sigma K structural genes and determined the properties of the resulting chimeric proteins in B. subtilis. The pro-sigma E-sigma K chimera accumulated and was cleaved into active sigma K, while the pro-sigma K-sigma E fusion protein failed to accumulate and is likely unstable in B. subtilis. A fusion of the sigE "pro" sequence to an unrelated protein (bovine rhodanese) also formed a protein that was cleaved by the pro-sigma E processing apparatus. The data suggest that the sigma E pro sequence contains sufficient information for pro-sigma E processing as well as a unique quality needed for sigma E accumulation.

Amino Acid Sequence↗

Simian immunodeficiency virus-specific cytotoxic T-lymphocyte induction through DNA vaccination of rhesus monkeys.

In view of the growing evidence that virus-specific cytotoxic T lymphocytes (CTL) play an important role in containing the early spread of human immunodeficiency virus type 1 (HIV-1) in infected individuals, novel vaccine strategies capable of eliciting HIV-1-specific CTL are being pursued in attempts to create an effective AIDS vaccine. We have used the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model to explore the induction of AIDS virus-specific CTL responses by DNA vaccination. We found that the inoculation of rhesus monkeys with plasmid DNA encoding SIVmac Env and Gag elicited a persisting SIVmac-specific memory CTL response. These CTL were CD8+ and major histocompatibility complex class I restricted. These studies provide evidence for the potential utility of DNA inoculation as an approach to an HIV-1 vaccine.

Animals↗

Simian immunodeficiency virus DNA vaccine trial in macaques.

An experimental vaccine consisting of five DNA plasmids expressing different combinations and forms of simian immunodeficiency virus-macaque (SIVmac) proteins has been evaluated for the ability to protect against a highly pathogenic uncloned SIVmac251 challenge. One vaccine plasmid encoded nonreplicating SIVmac239 virus particles. The other four plasmids encoded secreted forms of the envelope glycoproteins of two T-cell-tropic relatives (SIVmac239 and SIVmac251) and one monocyte/macrophage-tropic relative (SIVmac316) of the uncloned challenge virus. Rhesus macaques were inoculated with DNA at 1 and 3, 11 and 13, and 21 and 23 weeks. Four macaques were inoculated intravenously, intramuscularly, and by gene gun inoculations. Three received only gene gun inoculations. Two control monkeys were inoculated with control plasmids by all three routes of inoculation. Neutralizing antibody titers of 1:216 to 1:768 were present in all of the vaccinated monkeys after the second cluster of inoculations. These titers were transient, were not boosted by the third cluster of inoculations, and had fallen to 1:24 to 1:72 by the time of challenge. Cytotoxic T-cell activity for Env was also raised in all of the vaccinated animals. The temporal appearance of cytotoxic T cells was similar to that of antibody. However, while antibody responses fell with time, cytotoxic T-cell responses persisted. The SIVmac251 challenge was administered intravenously at 2 weeks following the last immunization. The DNA immunizations did not prevent infection or protect against CD4+ cell loss. Long-term chronic levels of infection were similar in the vaccinated and control animals, with 1 in 10,000 to 1 in 100,000 peripheral blood cells carrying infectious virus. However, viral loads were reduced to the chronic level over a shorter period of time in the vaccinated groups (6 weeks) than in the control group (12 weeks). Thus, the DNA vaccine raised both neutralizing antibody and cytotoxic T-lymphocyte responses and provided some attenuation of the acute phase of infection, but it did not prevent the loss of CD4+ cells.

Animals↗

[Prevention and treatment effect of niacin on FES: experimental study].

OBJECTIVE: On the basis of fat embolism syndrome animal model injected with homologous dog bone marrow fat, we probed into the prevention and treatment effect of niacin on FES. METHODS: Fourteen dogs were divided into experimental group and control group. In the experimental group, the dogs were injected with homologous dog bone marrow fat accompanied by niacin injection 4 mg/kg. 8 hr intravenously for 48 hours, while in the control group, only bone marrow fat was injected. PaO2, FFA, triglyceride, platelet counts, fat drops in the blood clots of vein were examined at different times. Finally, morphology and pathology of the lungs were observed. RESULTS: There were a slower decrease in PaO2 and platelet counts and no obvious increase in triglycerides and FFA in the experimental group. The amount and diameter of fat drops in the blood clots of vein and in the lungs were less in the experimental group than in the control. Pathological examinations of the lungs demonstrated much less injuries in the experimental group. CONCLUSION: Good prevention and treatment effect of niacin on fat embolism syndrome is suggested.

Animals↗