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Biomedical subjects

L Cheng

Publications and source records attributed to L Cheng.

At least 343 records · Page 19Linked to original sources

Modulation of calcium homeostasis in cultured rat aortic endothelial cells by intracellular acidification.

Acidosis produces vasodilation in a process that may involve the vascular endothelium. Because synthesis and release of endothelium-derived vasodilatory substances are linked to an increase in cytosolic calcium concentration ([Ca2+]i), we examined the effect of intracellular acidification on cultured rat aortic endothelial cells loaded either with the pH-sensitive probe carboxy-seminaphthorhodafluor-1 or the Ca(2+)-sensitive fluorescent probe indo 1. The basal cytosolic pH (pHi) of endothelial monolayers in a 5% CO2-HCO3- buffer was 7.27 +/- 0.02 and that in a bicarbonate-free solution was 7.22 +/- 0.03. Acidification was induced either by removal of NH4Cl (delta pHi = -0.10 +/- 0.02), changing from a bicarbonate-free to a 5% CO2-HCO3(-)-buffered solution at constant buffer pH (delta pHi = -0.18 +/- 0.03), or changing from a 5% to a 20% CO2-HCO3- solution (delta pHi = -0.27 +/- 0.07). Regardless of the method used, intracellular acidification increased [Ca2+]i as indexed by indo 1 fluorescence. The increase in [Ca2+]i induced by changing from a 5 to a 20% CO2-HCO3- solution was not significantly altered by removal of buffer Ca2+ either before or after depletion of bradykinin- and thapsigargin-sensitive intracellular Ca2+ stores. Thus intracellular acidification of vascular endothelial cells releases Ca2+ into the cytosol either from pH-sensitive intracellular buffer sites, mitochondria, or from bradykinin- and thapsigargin-insensitive intracellular stores. This Ca2+ mobilization may be linked to endothelial synthesis and release of vasodilatory substances during acidosis.

Acids↗

Effect of phosphorus restriction on renal response to oral and intravenous protein loads in rats.

Dietary phosphorus restriction ameliorates renal injury in rats. This may be due to changes in renal hemodynamics, including those factors associated with protein-induced hyperfiltration. To test this, we measured inulin clearance (CIn), p-aminohippuric acid clearance (CPAH), mean arterial blood pressure, and renal vascular resistance (RVR) 1 h before and 100 min after either oral gavage of 2 g bovine serum albumin or intravenous infusion of 5% glycine in female Sprague-Dawley rats previously fed for 3-8 wk a 0.5% or a 0.1% phosphorus diet. Baseline CIn, CPAH, blood pressure, and RVR were similar. After albumin gavage, CIn rose 20% (P < 0.01) for the 0.5% phosphorus group but did not change for rats fed the 0.1% phosphorus diet. Other measured parameters, including plasma glucagon and renin activity, were not influenced by dietary phosphorus content. In contrast, during intravenous infusion of glycine, hyperfiltration was induced in phosphorus-restricted rats. Thus dietary phosphorus restriction ablates oral protein but not intravenous amino acid-induced hyperfiltration, suggesting a gut-mediated mechanism for the former. These data highlight the potential importance of dietary phosphorus as a mediator of renal hemodynamics.

Administration, Oral↗

The effect of mifepristone (RU486) on the immunohistochemical distribution of prostaglandin E and its metabolite in decidual and chorionic tissue in early pregnancy.

The widespread tissue distribution of prostaglandin dehydrogenase (PGDH), the main enzyme for the metabolism and deactivation of prostaglandin (PG), suggests that local effective levels of PG are controlled by catabolism. Previous reports have suggested that after the administration of mifepristone (RU486) in vivo, the levels of PGDH in uterine tissues fall, such results support earlier suggestions that PGDH is under progesterone control in reproductive tissues. In this study we have used immunohistochemistry to assess tissue concentrations of PGE and its main metabolite 13,14-dihydro-15-keto-PGE in chorionic villi and decidua from women treated with RU486 12, 24, and 36 h previously. In control villous tissue, PGE and 13,14-dihydro-15-keto-PGE2 (PGEM) are prominent in the syncytiotrophoblastic layer, whereas PGE stains only weakly in cytotrophoblasts, due to the presence of PGDH in this region; treatment with RU486 in vivo causes little change in distribution or intensity in villi. However, in decidua, staining for PGE2 was intense in the glands after RU486 and localized in the supranuclear region of the cells. Small blood vessels that were PGE negative and PGEM positive in the controls were PGE positive and PGEM negative in treated tissue. These findings show that PG stimulation by antiprogestin is by means of a direct effect on PGDH, and secondly, that the prominent rise in PGE in blood vessels may be a major mode of action of this steroid in causing abortion, as PGs may synergize with leukocyte chemotactic agents to stimulate neutrophil ingress and tissue destruction.

Chorionic Villi↗

Malignant fibrous histiocytoma of the trachea combined with thymic carcinoma--a case report.

A 58-year-old woman was hospitalized in our hospital on July 9, 1988 with the chief complaint of progressive dyspnea for three months. She had been treated as bronchial asthma before she came to our hospital. During the hospitalization, bronchoscopic examination showed a lobulated mass arising from the left anterior lateral wall of the middle trachea. Chest CT scans showed two lesions: one was a nodular protruding mass in the middle trachea; the other was a soft tissue mass at the left thymic area. We performed a total resection of the tracheal tumor and partial resection of the mediastinal tumor. The pathological diagnosis was malignant fibrous histiocytoma of the trachea and squamous cell thymic carcinoma.

Carcinoma, Squamous Cell↗

Flow-dependent cytosolic acidification of vascular endothelial cells.

Hemodynamic shear stress affects endothelial cell structure and function, but little is known about the signal transduction mechanisms involved in these processes. The effect of laminar shear stress on cytosolic pH (pHi) was examined in rat aortic endothelial cells cultured in glass capillary tubes. Shear stress forces led to a rapid decrease in pHi (maximal effect 0.09 pH unit at 13.4 dynes per square centimeter). Removal of specific ions or addition of exchange inhibitors suggests that in vascular endothelial cells shear stress forces activate both an alkali extruder, sodium ion-independent chloride-bicarbonate ion exchange, and an acid extruder, sodium-hydrogen ion exchange; the net effect in physiologic buffer with the bicarbonate ion is a decrease in pHi.

Animals↗

Long-term proliferation of mouse primordial germ cells in culture.

Primordial germ cells (PGCs) are first identifiable as a population of about eight alkaline phosphatase-positive cells in the 7.0 days postcoitum mouse embryo. During the next 6 days of development they proliferate to give rise to the 25,000 cells that will establish the meiotic population. Steel factor is required for PGC survival both in vivo and in vitro and together with leukaemia inhibitory factor stimulates PGC proliferation in vitro. In feeder-dependent culture, PGCs will proliferate for up to 7 days, but their numbers eventually decline and their proliferative capacity is only a fraction of that seen in vivo. Here we report a further factor that stimulates PGC proliferation in vitro, basic fibroblast growth factor (bFGF). Furthermore, bFGF, in the presence of steel factor and leukaemia inhibitory factor, stimulates long-term proliferation of PGCs, leading to the derivation of large colonies of cells. These embryonic germ cells resemble embryonic stem cells, pluripotent cells derived from preimplantation embryos, or feeder-dependent embryonal carcinoma cells, pluripotent stem cells of PGC-derived tumours (teratomas and teratocarcinomas). To our knowledge, these results provide the first system for long-term culture of PGCs.

Animals↗

Synthesis and biological activity of ketomethylene pseudopeptide analogues as thrombin inhibitors.

Ketomethylene pseudopeptide analogues Aa-Pro-Arg psi (COCH2) Gly-pip, 1, where Aa are D- or L-amino acids (Dpa, beta, beta-diphenylalanine; alpha Nal, alpha-naphthylalanine; beta Nal, beta-naphthylalanine; Fgl, fluorenylglycine) with highly lipophilic side chains and psi (COCH2) is a ketomethylene pseudopeptide bond, have been synthesized through a modified Dakin-West reaction under very mild conditions with a high yield using tripeptide 4 with a labile functional group directly on the side chain. Their enzymatic assay of thrombin inhibition has been carried out. The structure-activity relationship study indicated that a lipophilic side chain on the amino acid in the P3 position is very important for binding to the apolar site of thrombin. Compound 1a with D-Dpa at the P3 position has a Ki of 0.2 microM and it doubles thrombin clotting time at only 3 times higher concentration. These values are about 7 times better than those of the corresponding D-Phe analogues. Furthermore, 1a shows poor inhibitory activity against plasmin, factor Xa, urokinase, and kallikrein. Preliminary in vivo testing (3-4-kg rabbit as the animal model) shows no observable side effect (change of blood pressure and accumulation of blood platelet in lungs) at a dose of 1 mg/kg.

Peptides↗

Authentic temperature-regulation of a heat shock gene inserted into yeast on a high copy number vector. Influences of overexpression of HSP90 protein on high temperature growth and thermotolerance.

Heat shock protein HSP90 is relatively abundant in eukaryotic cells even in the absence of heat shock. Its precise function is still unclear, although it is apparently required in higher levels for growth at high temperatures. In this study Saccharomyces cerevisiae transformants were constructed with 50-150 copies of the homologous heat-inducible gene for HSP90 (HSP82) present on a high copy number episomal vector. These transformants were then used to demonstrate: (i) that this heat shock gene displays essentially normal regulation when present in yeast at high copy numbers; (ii) that yeast is an expression host suitable for the high level synthesis of HSP90; and (iii) that increasing normal cellular levels of HSP90 affects a number of physiological properties. The HSP82 gene is normally single-copy in the haploid yeast genome, yet even at 50 to 150 copies per cell it displayed almost normal basal and heat shock-induced levels of expression. Proper regulation of the heat shock element sequence controlling HSP82 is therefore not lost at high gene copy levels. In unstressed cultures in exponential growth at 25 degrees C the low basal expression of the multiple HSP82 gene copies caused a 3 to 7-fold HSP90 overproduction, but HSP90 levels increased 10-fold to 30-40% of total cell protein following temperature upshift to 39 degrees C for 75 min. Heat induction of the chromosomal genes for other heat shock proteins in the same cells was not suppressed relative to cells which were isogenic but for the possession of just a single HSP82 gene, this constituting further evidence that yeast can authentically regulate a large number of heat shock genes. HSP90 overproduction was not protective against heat killing, causing strain-dependent reductions in growth at 37.5 degrees C and in thermotolerance.

Autoradiography↗

Restrained front seat car occupant fatalities--the nature and circumstances of their injuries.

The circumstances of a rural and urban sample of fatalities in vehicles less than six years old is described. The data originate from an in-depth, multidisciplinary study of accidents conducted in England since 1983. The sample is biased towards collisions that result in occupant injury, and this paper will concentrate on those accidents in which an occupant has been fatally injured. The initial police reporting of the fatalities included 11% of the deaths occurring from natural causes. Of the crash-related deaths with complete data, some 43% were frontal and lateral impacts, and they are analysed in greater detail. Thirty-six percent of restrained occupants died in lateral collisions. In both frontal and lateral crashes, large amounts of intrusion result in direct loading of the head and chest, particularly. Under-run crashes with large trucks constitute 30% of frontal death cases, and only 12% of fatalities received fatal injuries from belt loads. Of those cases, additional loading by unrestrained rear passengers could have been an important feature. Multiplicity of severe injuries is the rule for restrained fatalities, with head injuries as the most common cause of death. Eighty-two percent died within an hour of their crashes. Some consequences for vehicle compatibility in crashes are discussed.

Accidents, Traffic↗

Problems associated with the measurement of mean circulatory filling pressure by the atrial balloon technique in anaesthetized rats.

To examine the existence of pressure equilibrium between tributary veins and the central vena cava during the mean circulatory filling pressure manoeuvre, pressures in the hepatic portal vein, renal vein, and inferior vena cava were determined at 4-s intervals over a 20-s period of circulatory arrest induced by inflating a right atrial balloon in normal blood volume, 10% volume depletion, and 10% volume expansion states in urethane-anaesthetized rats. Portal vein pressure determined 8 s after arrest during volume depletion and expansion was significantly higher than vena caval pressure (6.2 +/- 0.8 vs. 3.4 +/- 0.2 and 7.7 +/- 0.5 vs. 6.2 +/- 0.4 mmHg (1 mmHg = 133.32 Pa), respectively; p less than 0.01); this pressure disequilibrium continued for 16 s during volume expansion and for the entire 20 s during volume depletion. Renal vein pressure was equal to vena caval pressure during this manoeuvre. Portal vein pressure at normal blood volume was not significantly different from vena caval pressure following circulatory arrest (4.6 +/- 0.3 vs. 3.8 +/- 0.4 mmHg, respectively). Following ganglionic blockade, portal vein pressure was still significantly higher than vena caval pressure for 12 s during volume alterations. At the 8th s of the arrest the portal pressure determined in volume depletion was 3.6 +/- 0.3 mmHg and the inferior vena caval pressure was 2.6 +/- 0.4 mmHg (p less than 0.05). Under the volume expansion condition, the respective values were 6.5 +/- 0.3 and 5.3 +/- 0.4 mmHg (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Migration of highly educated Asians and global dynamics.

The migration of highly educated Asians to developed countries and the implications of those movements are examined. "The far-reaching effects of the movement of Asian high level manpower (HLM) are discussed in light of: 1) the global articulation of higher education; 2) the link to unequal development on a global scale; and 3) the contribution to economic development of the reverse flow of HLM to less developed countries." The focus is on migration to Australia, Canada, and the United States from the 1960s to the present.

Americas↗

Human papillomavirus identified by nucleic acid hybridization in concomitant nasal and genital papillomas.

Presence of human papillomavirus (HPV) as the etiologic agent in nearly all upper respiratory tract recurrent papillomas is well-established. The technique of nucleic acid hybridization now allows specific typing of HPV with a high degree of accuracy. This article reports a series of nine consecutive patients treated for nasal papillomas over the past 9 years. Eight of these patients had a personal history of genital papillomas (seven patients) or exposure (one patient). With the use of in situ hybridization and autoradiographic technique on paraffin-embedded tissue sections, HPV RNA type 6/11 was expressed in eight of nine nasal papillomas, and corresponding HPV types were also found in the two cases with which concurrent anogenital papilloma tissue was also available for analysis. Human papillomavirus RNA types 16 and 18 were not detected in any of the specimens. Signals of HPV messenger RNA type 6/11 were stronger in the fungiform areas than in the inverted areas of papillomas.

Adult↗

Glycosphingolipids of rabbit endometrium and their changes during pregnancy.

The glycolipids of nonpregnant and pregnant rabbit endometrium were characterized using a combination of biochemical and immunochemical techniques. Quantitative analyses indicated a 70% decline in acidic glycolipid (ganglioside) content during early pregnancy (day 6), and a 2.5-fold increase in neutral glycolipid content during later pregnancy (day 26). The major gangliosides of rabbit endometrium were identified by thin-layer chromatography as GM3 and GD3, with minor amounts of GM1, GD1a and GT1b. The major neutral glycolipids were identified similarly as globo-series structures Gb3 and Gb4. Monoclonal antibodies (mAbs) directed to glycolipid antigens permitted the detection of additional glycolipid species, including sialylated, sulfated and fucosylated lacto-series structures. Difucosyl Ley structure (defined by mAb AH-6) and sulfated-galactosyl structure (defined by mAb VESP 6.2) were identified by indirect immunofluorescence along the luminal surface of the endometrium during the implantation period. Rapid changes in the glycolipid composition of endometrial cells during early pregnancy may facilitate embryo adhesion and trophectoderm outgrowth during implantation.

Animals↗

Immunohistochemical identification of cytotoxic lymphocytes using human perforin monoclonal antibody.

Perforin is a potent cytolytic pore-forming protein expressed in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells. A new monoclonal antibody raised against human perforin was used to detect both in vitro and in vivo perforin expression in cytotoxic cells. Immunohistochemical analysis of human peripheral blood mononuclear cells cultured in recombinant interleukin-2 (rIL-2) showed strong granular cytoplasmic staining of the IL-2 activated cytotoxic cells. Fresh-frozen tissue sections from patients with heart allograft rejection were also stained. Strong granular cytoplasmic staining of the mononuclear inflammatory infiltrate characteristic for perforin in cardiac allograft rejection was observed. The detection and quantitative analysis of perforin-associated cytotoxic cells by the human anti-perforin monoclonal antibody will help to evaluate the significance of these functionally distinct cytotoxic cells in human tissue.

Antibodies, Monoclonal↗