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Biomedical subjects

P T Lee

Publications and source records attributed to P T Lee.

At least 19 recordsLinked to original sources
PubMed2007

A preliminary report of brain edema in patients with uremia at first hemodialysis: evaluation by diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: The dynamics of brain-water content associated with hemodialysis in patients with severe azotemia remains obscure. To investigate whether either interstitial or cytotoxic edema is responsible for dialysis disequilibrium syndrome (DDS), we used diffusion-weighted MR imaging (DWI) to measure the apparent diffusion coefficient (ADC), which is sensitive for detecting tissue water dynamics. METHODS: Eight consecutive patients with end stage renal disease (ESRD) and blood urea nitrogen level of more than 100 mg/dL (160.9 +/- 53.1 mg/dL) were recruited. Conventional MR images, DWI, and clinical manifestations were obtained before and after the 1st hemodialysis. The ADC values were determined for regions of normal-appearing gray and white matter and for regions of hyperintensity of white matter on T2-weighted MR imaging. RESULTS: Foci of bright areas of white matter were found in all patients on T2-weighted images. The ADC values of the patients with ESRD, in white matter and gray matter before and after hemodialysis, were greater than those of the healthy controls (P < .005). Regarding the impact of hemodialysis, the ADC of frontal lobe white matter increased significantly after hemodialysis (1.09 +/- 0.11 versus 1.03 +/- 0.11, P = .036). We did not find the specific area of brain edema reported in posterior leukoencephalopathy and the osmotic demyelination syndrome. CONCLUSIONS: These results suggest that severe azotemia in end stage renal disease leads to interstitial brain edema reflected as increased ADC, and the further increased ADC reflects that edema associated with 1st hemodialysis is interstitial rather than cytotoxic in nature.

Adult↗
PubMed2004

Tuberculosis in patients with end-stage renal disease.

OBJECTIVE: To elucidate the clinical manifestations and risk factors of the mortality rate in uraemic patients with tuberculosis (TB) infection. DESIGN: We retrospectively analysed 62 patients with uraemia and active tuberculosis who were admitted to our hospital from 1990 through 2000. The patients were followed up for 2 years after discharge or until death. RESULTS: There were 43 men and 19 women, with a mean age of 63 +/- 13 years. Extra-pulmonary TB was noted in 51.6%. The peritoneum and pleura were the two most common organs involved. Fever of unknown origin was the most common manifestation (77.4%). The corrected serum Ca2+ level of the patients was >10.5 mg/dl in 46.8%. C-reactive protein >6 mg/dl and leukocytosis (white blood cell count >10,000/mm3) at presentation were noted in more than half of the patients. A reversed serum albumin/globulin ratio and leukocytosis were found to be associated with mortality rate. CONCLUSION: More than half of the TB infections in patients with end-stage renal disease presented with extra-pulmonary involvement. Fever of unknown origin, reversed serum albumin/globulin ratio, and unexplained hypercalcaemia in maintenance dialysis patients suggested the possibility of tuberculosis.

Age Distribution↗
PubMed2002

Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood mononuclear cells from atopics vs. non-atopics.

BACKGROUND: T helper (Th)2 cytokines are considered to play a central role in the induction and expression of allergic disease. However, the relative importance of individual cytokines is unclear, and overall disease pathogenesis appears to involve the coordinate activities of a range of Th2 cytokines acting in sequence or in parallel. The present study examines an alternative approach to the study of cytokine gene function in atopy, focusing instead upon T cell transcription factors (TFs) which play a role in the regulation of multiple cytokine genes. OBJECTIVE: To investigate the allergen-induced expression of the TF GATA-3 and c-Maf in peripheral blood mononuclear cells (PBMCs) and in cytokine-driven Th polarization. METHODS: PBMC from house dust mite (HDM)-atopic and non-atopics were stimulated in vitro with allergen or anti-CD3/IL-2. TF expression was analysed by semiquantitative RT-PCR and major findings were validated by real-time PCR. Cell separations were performed to analyse the contribution of CD45RO+ cells. CD4+ cord blood cells were Th1 or Th2 polarized in vitro by exogenous cytokines and TF expression analysed by Northern blot and real-time PCR. Results We demonstrate for the first time that during differentiation of CD4+ CD45RA+ naïve human T cells towards Th2 commitment, and during allergen-specific reactivation of peripheral CD4+ CD45RO+ Th2 memory cells in established atopics, expression of the Th2-associated TF GATA-3 is rapidly up-regulated, whereas T cells from non-atopics display equally rapid GATA-3 down-regulation under identical conditions of allergen stimulation. CONCLUSION: These findings identify Th2-associated TFs as key determinants of the atopic phenotype, suggesting their unique potential as therapeutic targets for disease control.

Adult↗
PubMed2001

Yeast COQ4 encodes a mitochondrial protein required for coenzyme Q synthesis.

The COQ4 gene coding for a component of the coenzyme Q biosynthetic pathway in the yeast Saccharomyces cerevisiae was cloned by a functional complementation of a Q-deficient mutant strain. Yeast coq4 mutant strains harboring the COQ4 gene on either single- or multicopy plasmids acquired the ability to grow on media containing a nonfermentable carbon source, synthesize Q(6), and respire. COQ4 encodes a polypeptide containing 335 amino acids with a calculated molecular mass of 38.6 kDa. By Western blot analysis with a specific antiserum, Coq4p was shown to peripherally associate with the matrix face of the mitochondrial inner membrane. The putative mitochondrial-targeting sequence present at the amino-terminus of the polypeptide efficiently imported it to mitochondria in a membrane-potential-dependent manner. Steady-state levels of COQ4 mRNA were increased during growth on glycerol-containing medium, in accordance with a function in Q biosynthesis. The function of Coq4p is unknown, although its presence is required to maintain a steady-state level of Coq7p, another component of the Q biosynthetic pathway. The results presented here, along with those available from literature, are discussed in light of the recently proposed existence of a multisubunit complex functioning in Q biosynthesis (A. Y. Hsu, T. Q. Do, P. T. Lee, and C. F. Clarke, 2000, Biochim. Biophys. Acta 1484, 287-297).

Alleles↗
PubMed2001

Ontogeny of rat pulmonary alveolar macrophage function: evidence for a selective deficiency in il-10 and nitric oxide production by newborn alveolar macrophages.

Alveolar macrophages (AM) play a crucial role in host defence by secretion of a large repertoire of biological response modifiers (BRM) following challenge. Newborns manifest increased susceptibility to lung infections, suggesting a deficiency in AM-mediated host defence. Thus, we investigated the ontogeny of BRM production by resting and stimulated AM. We analysed the capacity of rat AM to produce mRNA specific for a range of cytokines including tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-10, IL-12, IL-18, and the enzyme inducible nitric oxide synthase, in response to in vitro lipopolysaccharide (LPS) challenge. We report that production of nitric oxide by newborn AM under conditions of maximal stimulation was impaired. In addition, expression of IL-10 was only minimally upregulated in AM from newborns in response to LPS compared to adults. Inability to upregulate expression of IL-10 appeared to be influenced by microenvironmental factors, since peritoneal macrophages from newborns responded to LPS with significant upregulation of IL-10. Furthermore, when newborn AM were precultured in vitro, IL-10 responsiveness to LPS was partially restored. In contrast, cytokines such as TNF-alpha, IL-1, IL-6, IL-12 and IL-18 appeared to be expressed at adult levels by newborn AM. These results demonstrate that there may be functional differences in AM of newborns compared to adults, and these may be specific to the tissue compartment.

Age Factors↗
PubMed2001

A defect in coenzyme Q biosynthesis is responsible for the respiratory deficiency in Saccharomyces cerevisiae abc1 mutants.

Ubiquinone (coenzyme Q or Q) is an essential component of the mitochondrial respiratory chain in eukaryotic cells. There are eight complementation groups of Q-deficient Saccharomyces cerevisiae mutants designated coq1-coq8. Here we report that COQ8 is ABC1 (for Activity of bc(1) complex), which was originally isolated as a multicopy suppressor of a cytochrome b mRNA translation defect (Bousquet, I., Dujardin, G., and Slonimski, P. P. (1991) EMBO J. 10, 2023-2031). Previous studies of abc1 mutants suggested that the mitochondrial respiratory complexes were thermosensitive and function inefficiently. Although initial characterization of the abc1 mutants revealed characteristics of Q-deficient mutants, levels of Q were reported to be similar to wild type. The suggested function of Abc1p was that it acts as a chaperone-like protein essential for the proper conformation and functioning of the bc(1) and its neighboring complexes (Brasseur, G., Tron, P., Dujardin, G., Slonimski, P. P. (1997) Eur. J. Biochem. 246, 103-111). Studies presented here indicate that abc1/coq8 null mutants are defective in Q biosynthesis and accumulate 3-hexaprenyl-4-hydroxybenzoic acid as the predominant intermediate. As observed in other yeast coq mutants, supplementation of growth media with Q(6) rescues the abc1/coq8 null mutants for growth on nonfermentable carbon sources. Such supplementation also partially restores succinate-cytochrome c reductase activity in the abc1/coq8 null mutants. Abc1/Coq8p localizes to the mitochondria, and is proteolytically processed upon import. The findings presented here indicate that the previously reported thermosensitivity of the respiratory complexes of abc1/coq8 mutants results from the lack of Q and a general deficiency in respiration, rather than a specific phenotype due to dysfunction of the Abc1 polypeptide. These results indicate that ABC1/COQ8 is essential for Q-biosynthesis and that the critical defect of abc1/coq8 mutants is a lack of Q.

Electron Transport↗
PubMed2001

Failure of MHC class II expression in neonatal alveolar macrophages: potential role of class II transactivator.

Neonatal peritoneal and blood macrophages are known to be ineffective in antigen-presentation functions, and this manifests as inefficient MHC class II expression in response to IFN-gamma. The underlying mechanisms responsible for this maturational deficiency have not been elucidated. We show here that MHC class II expression in alveolar macrophages (AM) from neonates is also refractory to IFN-gamma stimulation. Furthermore, by examining the intracellular pathway leading to MHC class II expression, we demonstrate that the site of the impairment is at the level of transcription. Thus, expression of mRNA encoding the class II transactivator (CIITA), MHC class II (RT1.B) and invariant chain (Ii) was low or undetectable in neonatal AM stimulated with concentrations of IFN-gamma that induced adult AM to up-regulate MHC class II expression. The failure of AM from young animals to express MHC class II was not due simply to deficient IFN-gamma receptor function since IFN-gamma-responsive genes such as IRF-1, IRF-2 and IP-10 were up-regulated in a dose-dependent manner from animals of all ages investigated. Importantly, the responsiveness of neonatal AM to IFN-gamma, as determined by MHC class II expression, could be modulated to adult levels when pre-cultured in vitro. This suggests that microenvironmental factors operative in vivo may play a role in suppressing the expression of MHC class II in AM from young animals. We have investigated the role of type I interferons but did not find them to be responsible for the inability of AM from young animals to induce MHC class II in response to IFN-gamma.

Aging↗
PubMed2001

Acute oxalate nephropathy induced by star fruit in rats.

In this study, we intend to establish a connection between star fruit and acute oxalate nephropathy and also investigate predisposing factors for its development. Male Sprague-Dawley rats of 180 to 200 g were assigned to four groups; namely, control, experimental, fasting, and water-deprivation groups. The former two groups were subjected to both fasting and water deprivation, whereas the latter two groups were subjected to either fasting or water deprivation, respectively. Except for tap water for controls, the remaining groups were administered 4 mL/100 g of body weight of sour star fruit juice with an oxalate concentration of 2.46 g/dL. After these procedures, serial measurement of serum creatinine levels and kidney pathological examination were performed. Peak serum creatinine levels in the control, experimental, fasting, and water-deprivation groups were 0.50 +/- 0.04, 1.46 +/- 0.26, 0.68 +/- 0.20, and 0.52 +/- 0.08 mg/dL, respectively. The experimental group had a greater peak serum creatinine level (P < 0.05). Mean serum creatinine levels of the experimental group days 0, 1, 2, 3, 4, and 5 were 0.43 +/- 0.03, 1.11 +/- 0.18, 1.31 +/- 0.27, 1.16 +/- 0.28, 0.8 +/- 0.26, and 0.82 +/- 0.28 mg/dL, respectively. Mean serum creatinine levels days 1 to 3 were greater than that day 0 (P < 0.05). Pearson's correlation analysis of peak serum creatinine level and kidney weight for the experimental group showed a significant correlation (R = 0.75; P < 0.05; n = 9). In addition to typical changes of oxalate nephropathy, kidney pathological examination showed many refractile oxalate crystals with all rainbow colors under polarized light microscopy in the experimental group. In conclusion, sour star fruit with abundant oxalate contents could cause acute oxalate nephropathy in rats under the conditions of fasting and water deprivation.

Acute Kidney Injury↗
PubMed2001

Rhabdomyolysis: an unusual feature with mushroom poisoning.

Rhabdomyolysis resulting from mushroom poisoning previously has been unreported in the literature. We present an outbreak of Russula subnigricans poisoning with rhabdomyolysis. The most severely ill patient presented with rhabdomyolysis, severe electrolyte disturbance (hyperkalemia, hypocalcemia), respiratory failure, acute renal failure, pulmonary edema, ventricular tachycardia, and circulatory shock. Mycotoxin may be the cause of rhabdomyolysis. In areas where mushroom gathering is common, mushroom poisoning should be included in the differential diagnosis of rhabdomyolysis.

Female↗
PubMed2000

Genetic evidence for a multi-subunit complex in the O-methyltransferase steps of coenzyme Q biosynthesis.

Coq3 O-methyltransferase carries out both O-methylation steps in coenzyme Q (ubiquinone) biosynthesis. The degree to which Coq3 O-methyltransferase activity and expression are dependent on the other seven COQ gene products has been investigated. A panel of yeast mutant strains harboring null mutations in each of the genes required for coenzyme Q biosynthesis (COQ1-COQ8) have been prepared. Mitochondria have been isolated from each member of the yeast coq mutant collection, from the wild-type parental strains and from respiratory deficient mutants harboring deletions in ATP2 or COR1 genes. These latter strains constitute Q-replete, respiratory deficient controls. Each of these mitochondrial preparations has been analyzed for COQ3-encoded O-methyltransferase activity and steady state levels of Coq3 polypeptide. The findings indicate that the presence of the other COQ gene products is required to observe normal levels of O-methyltransferase activity and the Coq3 polypeptide. However, COQ3 steady state RNA levels are not decreased in any of the coq mutants, relative to either wild-type or respiratory deficient control strains, suggesting either a decreased rate of translation or a decreased stability of the Coq3 polypeptide. These data are consistent with the involvement of the Coq polypeptides (or the Q-intermediates formed by the Coq polypeptides) in a multi-subunit complex. It is our hypothesis that a deficiency in any one of the COQ gene products results in a defective complex in which the Coq3 polypeptide is rendered unstable.

Enzyme Stability↗
PubMed2000

Role of alveolar macrophages in innate immunity in neonates: evidence for selective lipopolysaccharide binding protein production by rat neonatal alveolar macrophages.

As the first line of defense against inhaled substances, alveolar macrophages (AM) play a crucial role in maintaining lung homeostasis. This is achieved via phagocytosis of foreign material and the secretion of a wide range of mediator molecules, including those involved in neutrophil recruitment. Neonates are known to manifest increased susceptibility to lung infections, and we hypothesize that this may be due in part to a deficiency in the function of AM. We report here that although recruitment of neutrophils into the respiratory tract of newborn animals in response to Moraxalla catarrhalis exposure is greatly delayed and diminished, AM from newborn animals have greater phagocytic capacity when compared with those from adult animals. Additionally, newborn AM respond normally to lipopolysaccharide (LPS) via production of a variety of chemokines, including macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, monocyte chemotactic protein-1, gro/ cytokine-induced neutrophil chemoattractant, MIP-2, and tumor necrosis factor-alpha. We have also demonstrated an LPS inducible expression of messenger RNA for LPS binding protein (LBP) in neonatal AM that was not observed in AM from adult animals or in peritoneal macrophages. We speculate that local production of LBP by AM may be a significant factor in the neonatal immunologic response to infections, providing a compensatory mechanism for the deficiency in specific neonatal immunity during this period of development when the newborn is being exposed to a range of potentially pathogenic materials for the first time.

Animals↗
PubMed1999

Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis.

Ubiquinone (coenzyme Q or Q) is a lipid that functions in the electron transport chain in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes. Q-deficient mutants of Saccharomyces cerevisiae harbor defects in one of eight COQ genes (coq1-coq8) and are unable to grow on nonfermentable carbon sources. The biosynthesis of Q involves two separate O-methylation steps. In yeast, the first O-methylation utilizes 3, 4-dihydroxy-5-hexaprenylbenzoic acid as a substrate and is thought to be catalyzed by Coq3p, a 32.7-kDa protein that is 40% identical to the Escherichia coli O-methyltransferase, UbiG. In this study, farnesylated analogs corresponding to the second O-methylation step, demethyl-Q(3) and Q(3), have been chemically synthesized and used to study Q biosynthesis in yeast mitochondria in vitro. Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. In addition, E. coli UbiGp was purified and found to catalyze both O-methylation steps. Futhermore, antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria. The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes and that Q biosynthesis is carried out within the matrix compartment of yeast mitochondria.

Animals↗
PubMed1998

Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity.

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2-3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-gamma by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing- associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor alpha or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.

Animals↗
PubMed1997

Characterization of the COQ5 gene from Saccharomyces cerevisiae. Evidence for a C-methyltransferase in ubiquinone biosynthesis.

Ubiquinone (coenzyme Q or Q) is a lipophilic metabolite that functions in the electron transport chain in the plasma membrane of prokaryotes and in the inner mitochondrial membrane of eukaryotes. Q-deficient mutants of Saccharomyces cerevisiae fall into eight complementation groups (coq1-coq8). Yeast mutants from the coq5 complementation group lack Q and as a result are respiration-defective and fail to grow on nonfermentable carbon sources. A nuclear gene, designated COQ5 was isolated from a yeast genomic library based on its ability to restore growth of a representative coq5 mutant on media containing glycerol as the sole carbon source. The DNA segment responsible for the complementation contained an open reading frame (GenBankTM accession number Z49210Z49210) with 44% sequence identity over 262 amino acids to UbiE, which is required for a C-methyltransferase step in the Q and menaquinone biosynthetic pathways in Escherichia coli. Both the ubiE and COQ5 coding sequences contain sequence motifs common to a wide variety of S-adenosyl-L-methionine-dependent methyltransferases. A gene fusion expressing a biotinylated form of Coq5p retains function, as assayed by the complementation of the coq5 mutant. This Coq5-biotinylated fusion protein is located in mitochondria. The synthesis of two farnesylated analogs of intermediates in the ubiquinone biosynthetic pathway is reported. These reagents have been used to develop in vitro C-methylation assays with isolated yeast mitochondria. These studies show that Coq5p is required for the C-methyltransferase step that converts 2-methoxy-6-polyprenyl-1, 4-benzoquinone to 2-methoxy-5-methyl-6-polyprenyl-1,4-benzoquinone.

Amino Acid Sequence↗
PubMed1997

A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene.

Strains of Escherichia coli with mutations in the ubiE gene are not able to catalyze the carbon methylation reaction in the biosynthesis of ubiquinone (coenzyme Q) and menaquinone (vitamin K2), essential isoprenoid quinone components of the respiratory electron transport chain. This gene has been mapped to 86 min on the chromosome, a region where the nucleic acid sequence has recently been determined. To identify the ubiE gene, we evaluated the amino acid sequences encoded by open reading frames located in this region for the presence of sequence motifs common to a wide variety of S-adenosyl-L-methionine-dependent methyltransferases. One open reading frame in this region (o251) was found to encode these motifs, and several lines of evidence that confirm the identity of the o251 product as UbiE are presented. The transformation of a strain harboring the ubiE401 mutation with o251 on an expression plasmid restored both the growth of this strain on succinate and its ability to synthesize both ubiquinone and menaquinone. Disruption of o251 in a wild-type parental strain produced a mutant with defects in growth on succinate and in both ubiquinone and menaquinone synthesis. DNA sequence analysis of the ubiE401 allele identified a missense mutation resulting in the amino acid substitution of Asp for Gly142. E. coli strains containing either the disruption or the point mutation in ubiE accumulated 2-octaprenyl-6-methoxy-1,4-benzoquinone and demethylmenaquinone as predominant intermediates. A search of the gene databases identified ubiE homologs in Saccharomyces cerevisiae, Caenorhabditis elegans, Leishmania donovani, Lactococcus lactis, and Bacillus subtilis. In B. subtilis the ubiE homolog is likely to be required for menaquinone biosynthesis and is located within the gerC gene cluster, known to be involved in spore germination and normal vegetative growth. The data presented identify the E. coli UbiE polypeptide and provide evidence that it is required for the C methylation reactions in both ubiquinone and menaquinone biosynthesis.

Alleles↗
PubMed1996

Motor vehicle accidents and TMDS: assessing the relationship.

Patients involved in a motor vehicle accident, or MVA, may experience signs and symptoms suggesting temporomandibular joint or masticatory muscle injury. Because there are no published clinical studies assessing the potential relationship among reported variables suggesting injury, examination findings, and crash impact and postural variables, the authors gathered data from 219 patients identifying TMD after an MVA. The results suggest that TMJ or masticatory muscle injury may be associated with varying postural characteristics and impact events, including speed, direction of impact and vehicular damage.

Acceleration↗
PubMed1986

Distal anastomotic obstruction with patent infrainguinal bypass.

Hemodynamic graft failure due to distal anastomotic obstruction was observed in 13 patients following femoropopliteal-tibial graft. The majority of such grafts (10 out of 13) had been performed with reversed saphenous vein. Graft patency was confirmed by arteriography in all cases, with retrograde flow in the majority of cases. Jump graft to a more distal site was performed in nine patients. Two early major amputations (within 30 days) and two late major amputations (30 days to 1 year) resulted. Return of ischemic symptoms, diminution of graft or distal pulses, and decrease in ankle pressures is an indication for arteriography. Undetected hemodynamic graft failure leads to thrombosis of the graft necessitating far more complicated operative procedures.

Femoral Artery↗