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Biomedical subjects

L Kong

Publications and source records attributed to L Kong.

At least 91 records · Page 5Linked to original sources
PubMed1995

T-lymphocyte subsets in acute illness.

OBJECTIVES: To determine the range of T-lymphocyte subsets (CD4, CD8, and CD4/CD8 ratios) in acutely ill, hospitalized patients and to determine whether these concentrations correlate with illness severity, survival rate, or immunodepression. DESIGN: Cross-sectional study, comparing Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and the calculated, disease-specific, predicted mortality rate with T-lymphocyte subsets. SETTING: Urban county hospital intensive care unit (ICU), serving as the designated trauma center. PATIENTS: One hundred two consecutively admitted ICU patients (72 medical and 30 surgical). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient clinical data, APACHE II scores, and their associated predicted mortality rate were recorded. Blinded human immunodeficiency virus (HIV) and lymphocyte testing was performed on samples from all patients on ICU admission. Despite only three (2.9%) of 102 patients testing positive for HIV antibodies, 41% (42/102) of patients had CD4 concentrations of < 400 cells/microL, and 29% (29/102) had CD4 concentrations of < 300 cells/microL. Mean CD8 concentrations were even lower, compared with normal laboratory values, resulting in a slight increase in CD4/CD8 ratios, although 16% (16/102) of patients had a CD4/CD8 ratio of < 1. CD4 counts were linearly related to total lymphocyte concentrations (Pearson correlation coefficient = 0.948), but no relationship was found between total lymphocyte or lymphocyte subset counts and APACHE II score, predicted mortality rate, or survival rate. CONCLUSIONS: Acute illness alone, in the absence of HIV infection, can be associated with profound decreases of T-lymphocyte populations. This problem is unpredictable and does not correlate with severity of illness, predicted mortality rate, or actual mortality rate. No conclusions regarding HIV serostatus or survival can be made based on single measurements of T-cell concentrations in acutely ill hospitalized patients.

APACHE↗
PubMed1995

comK encodes the competence transcription factor, the key regulatory protein for competence development in Bacillus subtilis.

comK is a positive autoregulatory gene occupying a central position in the competence-signal-transduction network. All regulatory routes identified in this network converge at the level of comK expression. The ComK protein is required for the transcriptional induction of comK and the late competence genes, which specify morphogenetic and structural proteins necessary for construction of the DNA-binding and uptake apparatus. In this report we demonstrate that ComK specifically binds to DNA fragments containing promoter and upstream sequences of the genes it affects (comC, comE, comF, comG and comK). Using portions of the region upstream of comC we show that the ComK-binding sequences are essential for the expression of competence. Moreover, we demonstrate that the presence of ComK stimulates the expression of comF-lacZ and comG-lacZ translational fusions in vivo in Escherichia coli. These results indicate that the gene product of comK is identical to the previously inferred competence transcription factor (CTF).

Amino Acid Sequence↗
PubMed1995

Evaluation of water-soluble pneumocandin analogs L-733560, L-705589, and L-731373 with mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis.

The activities of the water-soluble pneumocandin derivatives L-733560, L-705589, and L-731373 were evaluated in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis and were compared with those of commercially available antifungal agents. Pneumocandins are inhibitors of 1,3-beta-D-glucan synthesis. In the aspergillosis model, L-733560 and L-705589 significantly prolonged the survival of DBA/2N mice challenged intravenously with Aspergillus fumigatus conidia. L-733560 and L-705589 exhibited efficacies comparable to that of amphotericin B (AMB) with 90% effective doses of 0.48, 0.12, and 0.36 mg/kg of body weight, respectively. Two mouse models of disseminated candidiasis were used to evaluate these compounds. In both models, mice were challenged intravenously with Candida albicans. In a C. albicans survival model with DBA/2N and CD-1 mice, the efficacy of L-733560 was comparable to that of AMB, while L-731373 and L-705589 were somewhat less active. In a previously described C. albicans target organ kidney assay, the pneumocandin analogs and AMB at doses of > or = 0.09 mg/kg were effective in sterilizing kidneys, while fluconazole and ketoconazole were considerably less active and did not sterilize kidneys when they were used at concentrations of < or = 100 mg/kg. Although orally administered L-733560 showed activity in both candidiasis models, its efficacy was reduced compared with that of parenterally administered drug. In a disseminated cryptococcosis mouse model that measures the number of CFU of Cryptococcus neoformans per gram of brain and spleen, L-733560 at 10 mg/kg was ineffective in reducing the counts in organs, while AMB at 0.31 mg/kg sterilized the organs. These results indicate that the pneumocandins may be beneficial as potent parenterally administered therapeutic agents for disseminated aspergillosis and candidiasis.

Animals↗
PubMed1995

VEGF gene expression is upregulated in electrically stimulated rat skeletal muscle.

Vascular endothelial growth factor (VEGF; also called vascular permeability factor) is a secreted mitogen with distinct target cell specificity for vascular endothelial cells. Hypoxia upregulates VEGF expression, making it a likely mediator of the angiogenesis that occurs in poorly perfused tissues. The purpose of this study was to determine whether VEGF gene expression is upregulated in chronically stimulated skeletal muscles, where hypoxia is thought to trigger the growth of blood vessels. The right anterior tibialis and extensor digitorum longus muscles of 12 rats were stimulated electrically (10 Hz, 300 microseconds pulses) for up to 21 days by way of the peroneal motor nerve. The contralateral muscles served as control. Northern analysis showed that VEGF mRNA levels increased by approximately sixfold after 4 days of stimulation and then decreased gradually over the next several days. VEGF mRNA levels were still elevated by two- to threefold after 21 days of stimulation. Higher VEGF mRNA levels in the early stages of muscle stimulation and gradually decreasing levels in later stages are consistent with a metabolic hypothesis in which tissue oxygenation controls VEGF expression. These studies support the hypothesis that VEGF has a physiological role in promoting angiogenesis in stimulated skeletal muscle.

Animals↗
PubMed1995

Opposing actions of transforming growth factor-beta and glucocorticoids in the regulation of fibronectin expression in the human placenta.

Alterations in the expression of extracellular matrix (ECM) proteins in the placenta and fetal membranes have been linked to parturition whether occurring before or at term. In the present study, we examined the individual and combined effects of transforming growth factor (TGF)-beta and dexamethasone (DEX) on the expression of oncofetal fibronectin (onfFN), i.e. a major ECM protein synthesized by placenta, in cytotrophoblasts isolated from human term placentas to establish a model system from which to evaluate the actions of positive and negative regulators of ECM protein expression in the human placenta. Cytotrophoblasts were maintained for 21=62 h in medium supplemented with 4% charcoal-stripped calf serum in the presence or absence of TGF-beta (2 ng/mL) and DEX (10(-7) mol/L). Levels of onfFN in culture media were determined by immunoassay. TGF-beta treatment alone induced approximately a 150% increase in media levels of onfFN after 21 and 45 h of culture when compared with control, whereas DEX treatment alone reduced levels of onfFN to 15% of control levels. Media levels of onfFN in cells treated with both TGF-beta and DEX were 40-90% of control levels. Similarly, treatment of cells with TGF-beta alone promoted a 100-250% increase in rates of FN synthesis and levels of FN messenger ribonucleic acid, whereas DEX treatment alone reduced these indices of FN expression to approximately 10% of control levels. In cells treated with TGF-beta and DEX, levels of ECM protein synthesis and FN messenger ribonucleic acid were between 30 and 100% of control values. Similar patterns of regulation of FN expression by TGF-beta and DEX were observed when experiments were carried out in serum-free medium. Our results suggest that during pregnancy, TGF-beta and glucocorticoids may be important opposing physiological regulators of placental ECM protein expression.

Adult↗
PubMed1995

Reduction of extracellular matrix protein expression in human amnion epithelial cells by glucocorticoids: a potential role in preterm rupture of the fetal membranes.

Low levels of expression of extracellular matrix (ECM) proteins in chorioamniotic membranes is a characteristic of prematurely ruptured membranes, a condition associated with 40% of preterm deliveries. In light of the rise in levels of glucocorticoids (GC) in amniotic fluid associated with preterm labor, in the present study we examined the effects of GC on the expression of major ECM proteins in cultures of amnion epithelial cells recovered after digestion of human term amnions. Amnion cells were maintained with and without 10(-7) mol/L dexamethasone (DEX), and levels of the ECM protein fibronectin (FN) were determined by enzyme-linked immunosorbent assay. DEX treatment reduced FN expression in amnion epithelial cells to 15-30% of control levels and reduced FN expression in placental cells to 30-50% of control levels. Conversely, DEX treatment weakly stimulated FN expression in chorion cell cultures. DEX treatment did not affect the total level of amnion cell protein, indicating that the effects of DEX in amnion cells did not result from a general reduction in protein synthesis. Cortisol and DEX reduced FN expression in amnion cells, with half-maximal effective concentrations of approximately 60 and 8 nmol/L, respectively. In immunoprecipitation studies, DEX treatment reduced FN and collagen III synthesis to 20% of control levels, suggesting that GC may coordinately reduce the synthesis of major ECM proteins in amnion cells. Similarly, DEX treatment reduced the levels of FN messenger ribonucleic acids in amnion cells to approximately 15% of control levels. DEX treatment also promoted a marked reduction in FN expression in amnion cells cultured in serum-free medium to 10-50% of control levels. Our results indicate that GC negatively regulate ECM protein expression in amnion epithelial cells, suggesting a potential role in the genesis of altered fetal membrane ECM protein expression associated with prematurely ruptured membranes.

Adult↗
PubMed1995

Early clinical experience with a hybrid bioartificial liver.

BACKGROUND: Severe liver failure is associated with high mortality. Orthotopic liver transplantation (OLT) is the only effective therapeutic modality; there is a need for a 'bridge' system to support patients until an organ becomes available. METHODS: A bioartificial liver (BAL) was used to treat 10 patients with severe liver failure. A plasmapheresis system was used to pump patient plasma through a module with porcine hepatocytes. Each treatment lasted 6-7 h. RESULTS: All patients tolerated the procedure(s) well. Eight patients underwent OLT following BAL treatment(s). There were two late deaths after recovery from liver failure. Five patients with increased intracranial pressure (ICP) and decerebration had ICP normalization, increased cerebral perfusion pressure and full neurologic recovery after OLT. There was improvement in the level of encephalopathy and a significant decrease in serum ammonia after BAL treatment(s). CONCLUSIONS: BAL treatment is safe and beneficial and can be successfully used as a 'bridge' to transplantation.

Adult↗
PubMed1995

In vivo evaluation of three acid-stable azalide compounds, L-701,677, L-708,299 and L-708,365 compared to erythromycin, azithromycin and clarithromycin.

L-701,677, L-708,299 and L-708,365 are novel azalide derivatives of erythromycin that exhibit improved acid stability over erythromycin, azithromycin and clarithromycin. The half-life in aqueous solution at pH = 2.1 of these compounds ranged from 0.3 hour for erythromycin to 16.2 hours for L-708,299. The rank order of half-life in acid solution from most to least stable was L-708,299 > L-701,677 > L-708,365 > azithromycin = clarithromycin > erythromycin. In a disseminated Streptococcus pyogenes mouse infection model, azithromycin and L-708,365 were slightly more efficacious than clarithromycin, L-701,677 and L-708,299; all 5 compounds being more active than erythromycin. In a Klebsiella pneumoniae pulmonary challenge mouse model, azithromycin, L-701,677, L-708,299 and L-708,365 were all equal in efficacy and at least four-fold more active than clarithromycin and erythromycin. Clarithromycin, L-708,365 and interestingly erythromycin, showed greater bacterial clearance than azithromycin, L-701,677 and L-708,299 in a localized infection model that measured clearance of Staphylococcus aureus from mouse thigh tissues. Our results indicate that L-701,677, L-708,299 and L-708,365 exhibit improved acid stability and were at least equally efficacious as presently marketed macrolide/azalide antibiotics.

Animals↗
PubMed1995

LAK cell mediated apoptosis of human bladder cancer cells involves a pH-dependent endonuclease system in the cancer cell: possible mechanism of BCG therapy.

Intravesical bacillus Calmette-Guerin (BCG) is an effective treatment for superficial bladder cancer. However, its mechanism has been only partially elucidated. We studied whether LAK cell killing of human bladder cancer cells occurs via apoptosis (programmed cell death) or necrosis. Fluorescent dye labeled T24 cells were observed to undergo morphologic changes associated with apoptosis in the presence of LAK cells when analyzed under a fluorescence microscope. Furthermore, analysis of the DNA isolated from the cytotoxic assay confirmed that the LAK cell induced death of the T24 cells occurred via apoptosis. By pretreating the LAK cells with antifibronectin antibodies, we were able to significantly inhibit the LAK cell killing of the T24 cells. The percentage of cytotoxicity was reduced from 50% to 13% (p = 0.001), and the apoptotic pattern seen on agarose gel electrophoresis was significantly diminished. There was no significant change in the viability of the LAK cells following treatment with the antibodies. Endonuclease isolation from human bladder cancer T24 cells demonstrated that these cells express a pH-dependent and not a Ca++/Mg++ dependent endonuclease. Significant degradation of a target DNA was observed only in pH 4 to pH 5.6 buffers containing endonuclease from T24 cells and not in pH 6 to pH 8 buffers containing endonuclease from T24 cells. The presence or absence of Ca++/Mg++ in the various pH buffers did not alter the endonuclease activity. Finally, we demonstrated that death of T24 cells can be induced by altering the intracellular pH of the cells to 5.6 or lower with the proton ionophore nigericin. We conclude that LAK cells induce T24 cells to undergo apoptosis and that this process involves the fibronectin molecule present on the LAK cell membrane. Furthermore, the cleavage postulate that, in vivo, LAK cells activated by IL-2 produced by BCG activated CD4+ cells may induce bladder cancer cells to undergo apoptosis. This may partially explain the mechanism whereby BCG achieves its therapeutic effect.

Antibodies↗
PubMed1995

Clinical analysis of steroid glaucoma.

PURPOSE: The authors accumulated 15 cases (26 eyes) of steroid glaucoma due to topical administration of dexamethasone or prednisolone. METHODS: From 1970 to 1990, 26 eyes in 15 cases were observed (bilateral 11 cases, unilateral 4 cases) including 12 right eyes and 14 left eyes. 10 cases were male and 5 cases female with age ranging from 14 to 52 years averaging 28 years. 25 eyes had the manifestation of chronic open angle glaucoma in the clinical course, and 1 eye simulated an acute glaucoma attack. RESULTS: All patients had taken antiglaucoma medication before coming to our hospital, but the IOP was over 6.7 kPa in 9 eyes. The C/D ratio was equal to or over 0.6 in 9 cases (16 eyes), and the values were inconsistent between both eyes in 55% of the patients. Treatment for glaucoma was immediate discontinuation of the steroids with antiglaucoma medication if necessary. Three eyes received filtering operations and 2 eyes had the removal of subconjunctival residual steroid. Normal IOP was restored in months up to a year. CONCLUSION: Dexamethasone or prednisolone were the easiest to induce steroid glaucoma when the patients had long-term use of steroid eyedrops.

Adolescent↗
PubMed1994

Regulation of competence-specific gene expression by Mec-mediated protein-protein interaction in Bacillus subtilis.

The expression of competence genes in Bacillus subtilis is controlled by a signal transduction cascade which increases the expression of a competence transcription factor (CTF, encoded by comK) during the transition from exponential growth to stationary phase. The transcription of CTF (ComK) is decreased by the product of the mecA gene, and this inhibition is relieved in response to an unknown signal received from upstream in the regulatory pathway. Inactivation of either mecA or another gene, mecB, results in overproduction of ComK. We show here that the concentration of MecA protein does not vary markedly with culture medium, as a function of growth stage, or in competent and noncompetent cells. We also show that MecA can interact directly with ComK. Finally, evidence is presented suggesting that MecB functions prior to MecA in the signaling pathway. A model is discussed which involves the sequestration of ComK by MecA binding and the release of the transcription factor when an appropriate signal is relayed to MecA by MecB.

Amino Acid Sequence↗
PubMed1994

Positive and negative hepatic regulation of the human type II phospholipase A2 gene.

To identify the elements which regulate the liver transcription of the human type II phospholipase A2 gene and its stimulation by interleukin 6, the 5' flanking region from -1614 to +806 and several 3' and 5' deleted fragments have been analyzed in CAT assays. Negative regulatory elements have been located in the regions -1614 to -326 and +20 to +806. The fragment -326 to +20 contains the main elements required for the transcription as well as for the stimulation by interleukin 6. Footprinting assays have been performed on this region and showed four protected elements, A [-35;-6], B [-125;-86], C [-209;-176], and D [-247;-211]. Deletion of element D enhanced the transcription of the reporter gene 10.5-fold compared to the [-326;+20]-CAT construct. Further deletions up to position -87 which removed both the elements B and C or the substitution of element C by a nonspecific sequence lowered the promoter activity to 23% and 70% of the control, respectively. These results indicate that element C binds positive regulatory factors and element D binds a negative regulatory factor. Furthermore, stimulation by interleukin 6 is lost when element C is substituted or deleted. As shown by the footprinting and band shift assays, the transcription factors C/EBP alpha and C/EBP beta can bind to elements C and D but the dissociation constant (Kd) of C/EBP alpha is 10 times lower for element C (0.6 nM) than for element D (5.8 nM). Band shift experiments using rat liver nuclear extracts showed that element C formed four heat stable complexes, some of which could be supershifted by anti C/EBP alpha antibodies. The binding of C/EBP factors to element C was confirmed by competition with previously described oligonucleotide and nucleotide substitution of element C. Band shift experiments using rat liver nuclear extracts showed that element D formed one major DNA-protein complex. This complex could be competed out by oligonucleotides containing a cAMP responsive element (CRE) but not by oligonucleotides containing the binding site of C/EBP. However, anti-CREB antibodies did not supershift this complex. Methylation interference experiments showed the involvement of a G nucleotide upstream to the sequence homologous to CRE in the binding of the hepatic nuclear factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

The regulation of competence transcription factor synthesis constitutes a critical control point in the regulation of competence in Bacillus subtilis.

comK, which encodes the competence transcription factor, is itself transcriptionally activated at the transition from exponential growth to stationary phase in Bacillus subtilis. MecA, a negative regulator of competence, also inhibits comK transcription when overexpressed, and a mecA null mutation results in comK overexpression. Although null mutations in mecA, as well as in another gene, mecB, are known to bypass the requirements for nearly all of the competence regulatory genes, the comK requirement is not suppressed by mecA inactivation. Various competence regulatory genes (comA, srfA, degU, abrB, sin, and spo0A) are shown to be required for the expression of comK. srfA transcription is shown to occur equally in cells destined for competence and those destined not to become competent. In contrast, comK transcription is restricted to the presumptive competent cells. These and other results are combined to describe a regulatory pathway for competence.

Bacillus subtilis↗
PubMed1993

Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection.

Erythema migrans recurred in a patient 6 months after a course of treatment with minocycline for Lyme disease. Polymerase chain reaction on heparinized peripheral blood at that time demonstrated the presence of Borrelia burgdorferi-specific DNA. The patient was seronegative by Lyme enzyme-linked immunosorbent assay but showed suspicious bands on Western blot. Findings of a Warthin-Starry stain of a skin biopsy specimen of the eruption revealed a Borrelia-compatible structure. Reinfection was not believed to have occurred. Further treatment with minocycline led to resolution of the erythema migrans.

Aged↗
PubMed1993

Sequence and properties of mecA, a negative regulator of genetic competence in Bacillus subtilis.

The development of competence in Bacillus subtilis is regulated by growth conditions and several regulatory genes. In complex media competence development is poor, and there is little or no expression of late competence genes. mec mutations permit competence development and late competence gene expression in complex media, and bypass the requirements for many of the competence regulatory genes. In this paper we describe the cloning and characterization of mecA. The mecA gene product acts negatively in the development of competence. Null mutations in mecA allowed expression of a late competence gene comG, under conditions where it is not normally expressed, including in complex media and in cells mutant for several competence regulatory genes. Overexpression of MecA from a multicopy plasmid resulted in inhibition of comG transcription. The DNA sequence of mecA was determined and the predicted gene product showed no significant similarity to any protein in the database. Expression of a mecA-lacZ translational fusion was constitutive during growth and did not vary significantly in the different media tested. The role of mecA in competence development and other stationary phase phenomena is discussed.

Amino Acid Sequence↗
PubMed1992

A novel inositol mono-phosphatase inhibitor from Memnoniella echinata. Producing organism, fermentation, isolation, physicochemical and in vitro biological properties.

A novel inositol mono-phosphatase inhibitor, L-671,776 (1), was discovered from a culture of the hyphomycete, Memnoniella echinata (ATCC 20928). 1 has a molecular weight of 388 and a molecular formula of C23H32O5. The mode of inhibition is non-competitive, with a Ki of 450 microM. It shows no inhibition of myo-inositol 1,4-bisphosphate 1-phosphatase or myo-inositol 1,4,5-triphosphate 5-phosphatase, although it weakly inhibits myo-inositol 1,4,5-triphosphate 3-kinase (IC50 = 3 mM). It elevates inositol monophosphates in rat parotid slices (EC50 approximately 3 mM), but abolishes agonist effects. It also produces short-lived contraction of guinea pig trachea at 300 microM.

Animals↗
PubMed1992

[Pharmacological studies on erzhi pills].

The experimental results show that Erzhi Pills can markedly increase the weights of immunological organs in mice and antagonize the immunosuppressive action of prednisolone. The diameter of SRID precipitating ring, the hemolytic ability of PFC and the clearance rate of i.v. charcoal particles in mice can all be increased by the pills. Erzhi Pills also protect mice from CCl4 intoxication. Steamed Ligustrum lucidum has the same action as Erzhi Pills.

Animals↗