Psoriasis and cardiovascular comorbidities with emphasis in Asia.

Psoriasis is traditionally considered a skin-specific disease with the exception of coexisting psoriatic arthritis. However, growing evidence suggests a link between psoriasis and other comorbidities. Cardiovascular comorbidity, in particular, is the focus of considerable research, due in part to the associated mortality and possible intervention. A common mechanism that may explain both psoriasis and atherosclerosis pathogenesis is of great interest and utility. The increase of Th1 and Th17 leading to chronic inflammation is thought to be a patho-denominator for both diseases. In addition, progressive adiposity and resultant metabolic syndrome are but the beginning steps in the "psoriatic march". In this article, we review the recent publications on cardiovascular risks in patients with psoriasis. We also examine the effects of psoriasis treatment, including the new biologics, on cardiovascular comorbidities. Although there is generally a lack of Asian research on this issue, we present the most recent pertinent findings from Taiwan.

Measurement of human erythrocyte C4d to erythrocyte complement receptor 1 ratio in cardiac transplant recipients with acute symptomatic allograft failure.

BACKGROUND: Complement activation has been recognized as a contributing factor to cardiac allograft dysfunction. Combined measurement of erythrocyte C4d (E-C4d) and complement receptor 1 (E-CR1) are potential biomarkers to monitor complement activity in patients with autoimmune diseases. We conducted a prospective study using CR1-2B11 monoclonal antibody to detect the E-C4d to E-CR1 ratio among our cardiac transplant recipients with acute symptomatic allograft failure. MATERIALS AND METHODS: Eight recipients with acute cardiac allograft failure and 72 healthy controls were included in this study. Levels of E-C4d and E-CR1 were measured by indirect immunofluorescence and flow cytometry. The results were utilized to determine the association between patient C4d staining, histological features, and clinical outcomes. RESULTS: Eight patients with nine episodes of sudden onset of graft failure and suspected antibody-mediated rejection (AMR) were included in this study. One patient who received emergent mechanical circulatory support was treated with plasmapheresis for his unstable hemodynamic status. The mean pretreatment left ventricular ejection fraction was 30.3%. No histological study demonstrated cellular rejection or AMR in any patient. There were two patients with positive C4d immunostaining. Three patients had four episodes of acute rejection with sudden death at home. The mean E-C4d/E-CR1 ratio in the study group (n = 9) was 0.22 +/- 0.07, and 0.12 +/- 0.10 in the control group (n = 72). As comparing both groups, we found the ratios were significant higher in the study group (P = .0003). CONCLUSIONS: Measurement of the E-C4d/E-CR1 ratio may be a noninvasive method for detecting acute rejection after cardiac transplantation.

Modelling fuel consumption in kerbside source segregated food waste collection: separate collection and co-collection.

Source separated food waste is a valuable feedstock for renewable energy production through anaerobic digestion, and a variety of collection schemes for this material have recently been introduced. The aim of this study was to identify options that maximize collection efficiency and reduce fuel consumption as part of the overall energy balance. A mechanistic model was developed to calculate the fuel consumption of kerbside collection of source segregated food waste, co-mingled dry recyclables and residual waste. A hypothetical city of 20,000 households was considered and nine scenarios were tested with different combinations of collection frequencies, vehicle types and waste types. The results showed that the potential fuel savings from weekly and fortnightly co-collection of household waste range from 7.4% to 22.4% and 1.8% to 26.6%, respectively, when compared to separate collection. A compartmentalized vehicle split 30:70 always performed better than one with two compartments of equal size. Weekly food waste collection with alternate weekly collection of the recyclables and residual waste by two-compartment collection vehicles was the best option to reduce the overall fuel consumption.

FISH diagnosis of partial trisomy 13 and tetrasomy 13 in a patient with severe trigonocephaly (C) phenotype.

An infant girl with manifestations resembling Optiz trigonocephaly (C) syndrome who died at age 6 days was found to have a complex chromosome abnormality with t(13;18)(q22;q23) and a recombinant chromosome 13 involving duplicated segments of 13q. Precise characterization was possible with the application of fluorescence in situ hybridization (FISH) using chromosome specific probes. The patient's phenotype is compared to that of other syndromes involving trigonocephaly.

Neonatal vallecular cysts and failure to thrive.

The case of a vallecular cyst in a neonate is described. The presentation was with failure to thrive. This previously unreported mode of presentation is discussed, and aspects of the management are emphasized. In particular, the value of flexible nasopharyngoscopy in assessing the neonatal laryngopharynx is highlighted.

Emergency peripartum hysterectomy in a teaching hospital in Eastern Taiwan.

This study aims to review the incidence, indications, risk factors and complications associated with emergency peripartum hysterectomy in a teaching hospital. We reviewed records of patients undertaking emergency peripartum hysterectomy performed at our institution from 1998 to 2004. Emergency peripartum hysterectomy was defined as one performed for haemorrhage unresponsive to other treatments <24 h after delivery. Eight cases of emergency peripartum hysterectomy were performed. The rate of peripartum hysterectomy was 0.25%. The main indications for hysterectomy were uterine atony and abnormal placentation. No maternal death occurred. Use of peripartum hysterectomy may become necessary in managing obstetrical haemorrhage refractory to other measures.

Mutation of a neutral amino acid in the transit peptide of rat mitochondrial malate dehydrogenase abolishes binding and import.

We have investigated the function of a leucine residue in the transit peptide of the rat mitochondrial malate dehydrogenase precursor using in vitro mutagenesis. Amino acid replacement of leucine 13 with glutamic acid and asparagine abolished import into mitochondria, while substitutions with proline, histidine, and arginine severely diminished uptake. In contrast, glutamine, tyrosine, valine, and alanine replacement resulted in normal levels of import, suggesting that there is a requirement for an uncharged residue at this position. Mutants involving rearrangements of the native sequence at positions 12-14 were imported as efficiently as the wild-type mitochondrial malate dehydrogenase, indicating that there was not an obligatory order of amino acid residues. However, deletion of leucine 13 resulted in diminished import. Binding studies with isolated mitochondria revealed that several position 13 mutants were deficient in binding to the mitochondrial surface, accounting for the reduced import of these proteins. This impairment could be distinguished from the effects due to decreased positive charge. We conclude that while translocation depends on the net positive charge, binding to the mitochondrial surface is mediated by uncharged residues within the transit peptides of mitochondrial precursor proteins.

The role of arginine residues in the rat mitochondrial malate dehydrogenase transit peptide.

Arginine residues in the transit peptides of mitochondrial precursors are proposed to be important for uptake into mitochondria. To study this further, we have used cassette mutagenesis to create site-specific amino acid replacements within the transit peptide of rat mitochondrial malate dehydrogenase. Plasmids containing mutant sequences were expressed in vitro and tested in a mitochondrial uptake system utilizing isolated rat liver mitochondria. Substitution for arginine at position 14 with asparagine, glutamine, or alanine decreased the relative import level by 20-30% compared to the wild-type sequence when assayed in 1-h uptake experiments. Although lysine substitution did not alter import, substitution with glutamic acid decreased import by 40%. Alanine substitution for arginines at both positions 14 and 15 also dramatically decreased import. Uptake was partially restored in this mutant when positive charge was inserted at a new location within the transit peptide. Time course experiments showed that the initial rates of import were decreased in these mutants, as were the relative amounts of incorporated protein. These results were best explained by the loss of positive charge following amino acid substitutions for the arginine residues and suggest that the role of the charge is to enhance the efficiency of membrane translocation.

Import of the malate dehydrogenase precursor by mitochondria. Cleavage within leader peptide by matrix protease leads to formation of intermediate-sized form.

The mitochondrial matrix enzyme malate dehydrogenase (MDH) is synthesized on cytoplasmic polysomes as a larger precursor (pMDH) with an NH2-terminal leader peptide of 24 amino acids. Import of in vitro synthesized MDH into mitochondria results in formation of the mature-sized subunit. We report here that the conversion of pMDH to mMDH occurs via two distinct cleavage events within the leader peptide. First, pMDH is cleaved to an intermediate form (iMDH) of MDH. Conversion of the precursor to the intermediate form is catalyzed by a protease localized to the mitochondrial matrix. The cleavage of pMDH to iMDH involves the removal of 15 amino acids from the NH2 terminus of the pMDH leader peptide. The iMDH is subsequently cleaved, also by a matrix protease, to mature MDH in a reaction which is O-phenanthroline-sensitive. Cleavage to iMDH and to mature MDH occurs prior to completion of translocation of the MDH polypeptide chain into the mitochondrial matrix.

Translocation of precursor proteins into the mitochondrial matrix occurs through an environment accessible to aqueous perturbants.

We have identified translocational intermediates generated during import of precursor proteins into the mitochondrial matrix and have characterized their association with mitochondrial membranes. Partially translocated forms of mitochondrial malate dehydrogenase (MDH) and ornithine transcarbamylase (OTC) were generated during import of the corresponding precursors (pMDH and pOTC) into mitochondria at 2 degrees C. Import at this temperature results in the formation of intermediate-sized MDH (iMDH) and OTC (iOTC) produced by the removal of a portion of the leader peptide, and in the production of mature-sized MDH. All of these forms contain NH2 termini located within the mitochondrial matrix, although the majority of their polypeptide chains remain extramitochondrial. All three are strongly associated with mitochondrial membranes, but can be extracted by protein denaturants such as urea. These translocational intermediates appear to be hydrophilic proteins, on the basis of their partitioning properties during extraction with the nonionic detergent Triton X-114. The data indicate that the translocation of polypeptide chains into mitochondria occurs in a microenvironment that is aqueous in nature and is mediated by integral membrane proteins.

Synthetic transit peptides inhibit import and processing of mitochondrial precursor proteins.

We have demonstrated that a synthetic peptide corresponding to the rat mitochondrial malate dehydrogenase (mMDH) transit peptide (TP-28) inhibits the binding of pre-mMDH to isolated mitochondria. Synthetic peptides derived from chloroplast transit peptide sequences, which have a similar net charge, did not inhibit import. In addition, this peptide (TP-28) inhibits import of ornithine transcarbamylase, another mitochondrial matrix protein, thus suggesting that common import pathways exist for both mMDH and ornithine transcarbamylase. A smaller synthetic peptide corresponding to residues 1-20 of the mMDH transit peptide (TP-20) also inhibits binding. However, several substitutions for leucine-13 in the smaller peptide relieve import inhibition, thus providing evidence that this neutral residue plays a crucial role in transit peptide binding to the mitochondrial surface. Proteolytic processing of pre-mMDH by a mitochondrial matrix fraction to both the mature and intermediate forms of mMDH was also inhibited by TP-28. The ability of synthetic peptides to inhibit distinct steps in the import of mitochondrial precursor proteins corresponds precisely to their ability to interact with the same components used by transit peptides on intact precursors. Furthermore, inhibition at multiple points along the import pathway reflects the functions of several independent structures contained within transit peptides.

Isolation of novel non-HLA gene fragments from the hemochromatosis region (6p21.3) by cDNA hybridization selection.

It has previously been shown that cDNA hybridization selection can identify and recover novel genes from large cloned genomic DNA such as cosmids or YACs. In an effort to identify candidate genes for hemochromatosis, this technique was applied to a 320-kb YAC containing the HLA-A gene. A short fragment cDNA library derived from human duodenum was selected with the YAC DNA. Ten novel gene fragments were isolated, characterized, and localized on the physical map of the YAC.

The use of genotyping to predict the phenotypes of human platelet antigens 1 through 5 and of neutrophil antigens in Taiwan.

BACKGROUND: The human platelet antigen (HPA) 1 through 5 and the human neutrophil antigen (HNA-1) systems are relevant to immune-related thrombocytopenia and neutropenia. The alloantigen distribution profiles in the population will aid in estimating the risk of alloimmunization. STUDY DESIGN AND METHODS: Genotyping of the genes that control the expression of the HPA-1 through -5 and HNA-1 systems in Taiwanese (n = 326) and Taiwan's indigenous peoples (n = 608) was performed by PCR with the sequence-specific primer (PCR-SSP) method. RESULTS: In the HPA system, HPA-1b and HPA-4b were absent among Taiwan's indigenous tribes and detected among other Taiwanese only with frequencies of <0.2 percent and <0.5 percent, respectively. The GP1BA*2 (HPA-2b) and GP1A*2 (HPA-5b) allele frequencies range from 1 percent to 7 percent and 0.4 percent to 3.5 percent among the two ethnic groups, respectively. GP2B*1 (HPA-3a) and GP2B*2 (HPA-3b) showed similar allele frequencies. In the HNA-1 system, the FCGR3B*1 (HNA-1a) allele frequency was about twice that of FCGR3B*2 (HNA-1b) in Taiwanese and also in most of the indigenous tribes. Three FCGR3B (HNA-1) null persons were found in one indigenous tribe (Ami tribe), for an FCGR3B null frequency of 19.8 percent. However, no FCGR3B*3 (HNA-1c) allele was detected in Taiwan. CONCLUSION: The frequencies of HPA-1b, -2b, and -5b in the Taiwanese population were much lower than those among whites. In Taiwan, all of the HNA-1 null found was due to the deletion of the FCGR3B gene, and this deletion may be widely distributed in the Ami tribe.

Cloning of a new "finger" protein gene (ZNF173) within the class I region of the human MHC.

The human major histocompatability complex contains genes of both immune and nonimmune importance. Recently, several genes encoding novel, non-HLA products have been described in this area. We have performed positional cloning of short fragment cDNA sequences from the class I region of the human MHC using a hybridization selection approach. This report describes isolation of full-length cDNA clones and partial genomic clones that encode a protein that contains two domains rich in cysteine and histidine similar to those characteristic of metal-dependent DNA binding proteins (C3HC4). The predicted protein also contains a domain thought to form a coiled-coil that may promote dimerization. A third feature is a polyglutamic acid region near the carboxyl terminus of the conceptual protein. Because of these properties, we have named this gene product acid finger protein (AFP). Although the biological role of AFP is unknown at present, one potential function is binding of nucleic acids. The gene (ZNF173) is expressed in multiple tissues and is conserved among mammals. In particular, the mouse and human coding regions are highly conserved. In addition to AFP, other related sequences have been localized to the MHC, suggesting that multiple AFP-like genes exist in this area.

Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue.

Medium-chain acyl-CoA dehydrogenase (MCAD; acyl-CoA: (acceptor) 2,3-oxidoreductase, EC 1.3.99.3) is one of three similar enzymes that catalyze the initial step of fatty acid beta-oxidation. Definition of the primary structure of MCAD and the tissue distribution of its mRNA is of biochemical and clinical importance because of the recent recognition of inherited MCAD deficiency in humans. The MCAD mRNA nucleotide sequence was determined from two overlapping cDNA clones isolated from human liver and placental cDNA libraries, respectively. The MCAD mRNA includes a 1263-base-pair coding region and a 738-base-pair 3'-nontranslated region. A partial amino acid sequence (137 residues) determined on peptides derived from MCAD purified from porcine liver confirmed the identity of the cDNA clone. Comparison of the amino acid sequence predicted from the human MCAD cDNA with the partial protein sequence of the porcine MCAD revealed a high degree (88%) of interspecies sequence identity. RNA blot analysis shows that MCAD mRNA is expressed in a variety of rat (2.2 kilobases) and human (2.4 kilobases) tissues. Blot hybridization of RNA prepared from cultured skin fibroblasts from a patient with MCAD deficiency disclosed that mRNA was present and of similar size to MCAD mRNA derived from control fibroblasts. The isolation and characterization of MCAD cDNA is an important step in the definition of the defect underlying MCAD deficiency and in understanding its metabolic consequences.

Extensive thrombophlebitis with reactive thrombocytosis in a high risk Chinese parturient associated with retained placenta increta: a case report.

Postpartum thrombophlebitis is an infrequent disorder in Chinese women. A case is reported of extensive postpartum thrombophlebitis involving 23 cm of the femoral and pelvic veins. This 25-year-old splenectomized victim of beta-thalassemia was bedridden for 12 weeks because of threatened premature labor before Cesarean delivery. During the operation, placenta increta with massive bleeding was encountered. To save the uterus, ten percent of the placenta was retained. Duplex color Doppler imaging was performed for the diagnosis and follow-up of the thrombosis and vigorous anticoagulation therapy successfully cured this patient.