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T Kwan

Publications and source records attributed to T Kwan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Vancomycin use in 2 Ontario tertiary care hospitals: a survey.

OBJECTIVE: Use of vancomycin is a risk factor for acquiring vancomycin-resistant enterococci (VRE). To optimize the use of vancomycin in hospitals, the Hospital Infection Control Practices Advisory Committee (HICPAC) published recommendations in 1995. The objectives of this study were to determine the frequency, indications, and risk factors for inappropriate inpatient vancomycin prescriptions before and after publication of the HICPAC recommendations. DESIGN: Cross-sectional study. SETTING: Two tertiary care hospitals in Ontario. INTERVENTIONS: Vancomycin prescriptions were randomly sampled and hospital chart view performed for two 12-month periods, one before and one after publication of the HICPAC recommendations on vancomycin use. RESULTS: Based on the review of 189 charts from hospital A and 190 from hospital B, there was no significant change in the proportion of inappropriate vancomycin prescriptions at either hospital from before publication of the HICPAC recommendations to afterward (63% v. 71% at hospital A, p = 0.21; 48% v. 37% at hospital B, p = 0.11). In 51% of all vancomycin prescriptions, the drug was prescribed instead of another antibiotic because of a recorded penicillin allergy. Surgical prophylaxis with more than 1 or 2 doses of vancomycin accounted for 66% (hospital A) and 58% (hospital B) of inappropriate prescriptions. In a multivariate analysis, surgical prophylaxis remained a significant risk factor for inappropriate use of vancomycin at both hospitals (odds ratio [OR] 5.6, 95% confidence interval [CI] 2.8 to 11.3, p = 0.01 for hospital A; OR 13.9, 95% CI 4.9 to 39.5, p = 0.01 for hospital B). Prescription by the orthopedic service also remained a significant risk factor in the final logistic regression model for hospital B (OR 3.9, 95% CI 1.1 to 13.9, p = 0.01). CONCLUSIONS: A high proportion of vancomycin prescriptions, surveyed before and after publication of the HICPAC recommendations on vancomycin use, were inappropriate. Excessive vancomycin use in surgical prophylaxis was an important factor. Our findings suggest that the use of standardized peri-operative order forms and of penicillin-allergy testing may help optimize vancomycin use in tertiary care hospitals.

Anti-Bacterial Agents↗
PubMed1998

Mutational analysis of the P-glycoprotein first intracellular loop and flanking transmembrane domains.

The role of individual intracellular (IC) loops linking transmembrane (TM) domains in P-glycoprotein (P-gp) function remains largely unknown. The high degree of sequence conservation of these regions in the P-gp family and other ABC transporters suggests an important role in a common mechanism of action of these proteins. To gain insight into this problem, we have randomly mutagenized a portion of TM2, the entire IC1 loop, TM3, the entire extracellular loop (EC2), and part of TM4, and analyzed the effect of such mutations on P-gp function. Random mutagenesis was carried out using Taq DNA polymerase and dITP under conditions of low polymerase fidelity, and the mutagenized segments were reintroduced in the full length mdr3 cDNA by homologous recombination in the yeast Saccharomyces cerevisiae strain JPY201. The biological activity of mutant P-gp variants was analyzed in yeast by their ability to confer cellular resistance to the antifungal drug FK506 and the peptide ionophore valinomycin, and by their ability to complement the yeast Ste6 gene and restore mating in a yeast strain bearing a null mutation [Raymond, M., et al. (1992) Science 256, 232-4] at this locus. The analysis of 782 independent yeast transformants allowed the identification of 49 independent mutants bearing single amino acid substitutions in the mutagenized segment resulting in an altered P-gp function. The mutants could be phenotypically classified into two major groups, those that resulted in partial or complete overall loss of function and those that seemed to affect substrate specificity. Several of the mutants affecting overall activity mapped in IC1; in particular we identified a segment of four consecutive mutation sensitive residues (TRLT, positions 169-172) with such a phenotype. On the other hand, we identified a cluster of mutants affecting substrate specificity within the short EC2 segment and in the adjacent portion of the neighboring TM4 domain. Expression and partial purification of a representative subset of these mutants showed that in all but two cases, loss of function was associated with loss of drug-induced ATPase activity of P-gp. Therefore, it appears that TM domains, IC and EC loops, are structurally and functionally tightly coupled in the process of drug stimulatable ATPase characteristic of P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

A comparison of role expectations and communication styles between transplant coordinators and transplant staff nurses.

The role of the transplant coordinator is multifaceted and demanding, requiring advanced clinical skills in addition to patient management responsibilities. Although much is known about the clinical skills of these coordinators, there is virtually no information available about their management abilities. A comparison of the beliefs of transplant coordinators and transplant staff nurses confirms that the coordinators have the role expectations and communication styles to allow them to function effectively in managing patient care as well as in working with physicians and other health professionals.

Adult↗
PubMed1998

Patients with type 2 diabetes have a high frequency of the C282Y mutation of the hemochromatosis gene.

OBJECTIVE: To determine whether a specific mutation (C282Y) associated with primary hemochromatosis (PHC) is more common in patients with type 2 diabetes than in a control group of patients with type 1 diabetes. Patients with type 2 diabetes have a two- to threefold higher rate of PHC than the general population. Recent identification of a genetic mutation in patients with PHC raises the possibility that the mutation is related to type 2 diabetes. DESIGN: Cross-sectional study. SUBJECTS: One hundred and five patients with type 2 diabetes and 103 control patients with type 1 diabetes, who attended the same tertiary care diabetes clinic, who were of European origin, and in whom there was no clinical suspicion of hemochromatosis. INTERVENTIONS: Patients completed a brief clinical assessment and provided a blood sample. Iron studies were measured in serum, and DNA was assayed for the presence of the C282Y and H63D mutations of the HFE gene. RESULTS: Twenty-three of 105 patients (21.9%, 95% confidence interval [CI] 14.0, 29.8) with type 2 diabetes (1 homozygote) and 12 of 103 patients (11.7%; 95% CI 5.5, 17.9) with type 1 diabetes (all heterozygotes) had at least 1 copy of the C282Y mutation (odds ratio [OR] = 2.1; 95% CI 1.0, 4.5; p = 0.048). Neither serum ferritin nor transferrin saturation level identified patients with a C282Y mutation. CONCLUSION: The C282Y gene mutation is a potential genetic marker for type 2 diabetes. It, or a closely linked gene, may be associated with greater than 20% of cases of type 2 diabetes.

Adolescent↗
PubMed1997

p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum.

We have identified a human Bcl-2-interacting protein, p28 Bap31. It is a 28-kD (p28) polytopic integral protein of the endoplasmic reticulum whose COOH-terminal cytosolic region contains overlapping predicted leucine zipper and weak death effector homology domains, flanked on either side by identical caspase recognition sites. In cotransfected 293T cells, p28 is part of a complex that includes Bcl-2/Bcl-XL and procaspase-8 (pro-FLICE). Bax, a pro-apoptotic member of the Bcl-2 family, does not associate with the complex; however, it prevents Bcl-2 from doing so. In the absence (but not presence) of elevated Bcl-2 levels, apoptotic signaling by adenovirus E1A oncoproteins promote cleavage of p28 at the two caspase recognition sites. Purified caspase-8 (FLICE/MACH/Mch5) and caspase-1(ICE), but not caspase-3 (CPP32/apopain/ Yama), efficiently catalyze this reaction in vitro. The resulting NH2-terminal p20 fragment induces apoptosis when expressed ectopically in otherwise normal cells. Taken together, the results suggest that p28 Bap31 is part of a complex in the endoplasmic reticulum that mechanically bridges an apoptosis-initiating caspase, like procaspase-8, with the anti-apoptotic regulator Bcl-2 or Bcl-XL. This raises the possibility that the p28 complex contributes to the regulation of procaspase-8 or a related caspase in response to E1A, dependent on the status of the Bcl-2 setpoint within the complex.

Amino Acid Sequence↗
PubMed1997

GIP(6-30amide) contains the high affinity binding region of GIP and is a potent inhibitor of GIP1-42 action in vitro.

GIP (Glucose-dependent Insulinotropic Polypeptide) is an important regulator of insulin secretion. The effects of truncated forms of the peptide, GIP(10-30), GIP(6-30amide) and GIP(7-30), on binding of 125I-GIP(1-42) to GIP receptors in transfected CHO-KI cells, and on cyclic AMP responses to GIP(1-42), have been studied with a view to defining further the receptor binding region of GIP, and to establish whether such truncated peptides exhibit agonist or antagonist activity. All three peptides were found to be receptor antagonists, however GIP(6-30amide) exhibited receptor binding affinity equivalent to that of GIP(1-42) in competitive binding studies (IC50 = 3.08+/-0.57 nM). GIP(6-30amide) inhibited GIP(1-42)-induced cAMP production by 58% at a concentration of 100 nM, whereas GIP(10-30) and GIP(7-30), inhibited only in the microM range. GIP(6-30amide) therefore contains the high affinity binding region of GIP and is a potent inhibitor of GIP(1-42) action in vitro.

Animals↗
PubMed1997

Cloning and characterization of the OsNramp family from Oryza sativa, a new family of membrane proteins possibly implicated in the transport of metal ions.

The mammalian Nramp1 protein is an integral membrane protein expressed exclusively in macrophages, where it plays a critical role in the ability of these cells to destroy ingested microbes. The bactericidal mechanism of action of Nramp1 remains unknown. We report the identification and characterization of cDNA clones corresponding to three homologues of the mammalian Nramp1 gene from the genome of Oryza sativa, OsNramp1, OsNramp2, and OsNramp3. These three genes encode a novel group of highly similar hydrophobic polypeptides sharing between 64% and 75% sequence similarity, that show similar hydropathy profiles, and predicted secondary structure, including the same number, position, and sequence characteristics (including conserved charges) of transmembrane domains. Together, these define a highly conserved membrane associated hydrophobic core. The three plant proteins show a remarkable degree of sequence similarity with their mammalian counterpart (60% to 70% similarity), including primary and secondary structure elements previously described in ion transporters and channels. Expression studies in normal plant tissues indicate that while OsNramp1 is expressed primarily in roots, and OsNramp2 is primarily expressed in leaves, OsNramp3 is expressed in both tissues. The recent discovery that the yeast Nramp homologue SMF1 functions as a manganese transporter raises the exciting possibility that OsNramp encodes a family of metal ion transporters in plants.

Amino Acid Sequence↗
PubMed1997

Pulsus alternans in diastolic left ventricular dysfunction--a case report.

Pulsus alternans is usually found in patients with reduced systolic ventricular function. We describe a patient with recurrent pulmonary edema, hypertension, bilateral renal artery stenosis, but with normal systolic function. Pulsus alternans was demonstrated in both pulmonary artery, right ventricle, and left ventricle pressures. After successful renal artery revascularization, the pulsus alternans disappeared. This case illustrates that pulsus alternans can be present with diastolic dysfunction of the left ventricle in the absence of systolic dysfunction.

Aged↗
PubMed1996

Mutagenesis of transmembrane domain 11 of P-glycoprotein by alanine scanning.

The biochemical and genetic analyses of P-glycoprotein (P-gp) have indicated that the membrane-associated regions of P-gp play an important role in drug recognition and drug transport. Predicted transmembrane domain 11 (TM11) maps near a major drug binding site revealed by photoaffinity labeling, and mutations in this domain alter the substrate specificity of P-gp. To investigate further the role of TM11 in P-gp function in general, and substrate specificity in particular, each of the 21 residues of TM11 of the P-gp isoform encoded by the mouse mdr3 gene was independently mutated to alanine, or to glycine in the case of endogenous alanines. After transfection and overexpression in Chinese hamster ovary cells, pools of stable transfectants were analyzed for qualitative or quantitative deviations from the profile of resistance to vinblastine, adriamycin, colchicine, and actinomycin D displayed by the wild-type protein. While mutations at eight of the positions had no effect on P-gp function, 13 mutants showed a 2-10-fold reduction of activity against one of the four drugs tested. Although the phenotype of individual mutants was varied, replacements at most mutation-sensitive positions seemed to affect the drug resistance profiles rather than the overall activity of the mutant P-gp. When TM11 was projected in a alpha-helical configuration, the distribution of deleterious and neutral mutations was not random but segregated with a more hydrophobic (mutation-insensitive) face and a more hydrophilic (mutation-sensitive) face of a putative amphipathic helix. The alternate clustering pattern of deleterious vs neutral mutations in TM11 together with the altered drug resistance profile of deleterious mutants suggest that the more hydrophilic face of the TM11 helix may play an important structural or functional role in drug recognition and transport by P-gp. Finally, the conservation of the two residues most sensitive to mutations (Y949 and Y953) in TM11, and in the homologous TM5, of all mammalian P-gps and also in other ABC transporters, suggests that these residues and domains may play an important role in structural as well as mechanistic aspects common to this family of proteins.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Nramp defines a family of membrane proteins.

Nramp (natural resistance-associated macrophage protein) is a newly identified family of integral membrane proteins whose biochemical function is unknown. We report on the identification of Nramp homologs from the fly Drosophila melanogaster, the plant Oryza sativa, and the yeast Saccharomyces cerevisiae. Optimal alignment of protein sequences required insertion of very few gaps and revealed remarkable sequence identity of 28% (yeast), 40% (plant), and 55% (fly) with the mammalian proteins (46%, 58%, and 73% similarity), as well as a common predicted transmembrane topology. This family is defined by a highly conserved hydrophobic core encoding 10 transmembrane segments. Other features of this hydrophobic core include several invariant charged residues, helical periodicity of sequence conservation suggesting conserved and nonconserved faces for several transmembrane helices, a consensus transport signature on the intracytoplasmic face of the membrane, and structural determinants previously described in ion channels. These characteristics suggest that the Nramp polypeptides form part of a group of transporters or channels that act on as yet unidentified substrates.

Amino Acid Sequence↗
PubMed1995

Coronary artery fistula coexisting with a ventricular septal defect due to a penetrating gunshot wound.

We describe a patient who survived a penetrating gunshot wound to the chest. Cardiac evaluation including echocardiography and cardiac catheterization revealed a coronary artery fistula and a ventricular septal defect. This combination has been rarely reported in patients with penetrating cardiac injury. Follow-up echocardiography performed 15 mo later showed persistent left-to-right shunt. This is the first case in the literature demonstrating the natural history of combined coronary artery fistula and ventricular septal defect without surgical correction.

Adult↗
PubMed1995

Intracoronary ST-T alternans during coronary balloon angioplasty.

To evaluate the presence and clinical significance of electrical alternans during PTCA, intracoronary electrocardiography (ic-ECG) was performed in 65 consecutive lesions. ST-T alternans, defined as a beat-to-beat difference in the ST elevation > or = 1 mm, was present in five lesions (7.7%), all in the proximal left anterior descending (LAD) coronary artery. The phenomenon was seen only after 130 sec (mean 174 +/- 57) of balloon inflation. Only two of the five showed ST-T alternans simultaneously on both surface and ic-ECG. One of five patients had premature ventricular contractions following ST-T alternans. Three of these five lesions required a second balloon inflation with duration of > or = 300 sec; there was no ST-T alternans on the second inflation in any of these lesions. We conclude: (1) the detection of ST-T alternans during PTCA is enhanced by use of ic-ECG, (2) electrical alternans during PTCA was seen only in proximal LAD lesions, implicating a large amount of ischemic myocardium as a requisite for the phenomenon, (3) electrical alternans is not immediate, requiring a certain duration of balloon occlusion and hence ischemia to occur, and (4) the absence of ST-T alternans during second balloon inflations suggests ischemic preconditioning may abolish this phenomenon.

Adult↗
PubMed1995

The macrophage-specific membrane protein Nramp controlling natural resistance to infections in mice has homologues expressed in the root system of plants.

In mice, natural resistance or susceptibility to infection with Mycobacteria, Salmonella, and Leishmania is controlled by a gene named Bcg. Bcg regulates the capacity of macrophages to limit intracellular replication of the ingested parasites, and is believed to regulate a key bactericidal mechanism of this cell. Recently, we have cloned the Bcg gene and shown that it encodes a novel macrophage-specific membrane protein designated Nramp. A routine search of the public databases for sequences homologous to Nramp identified 3 expressed sequence tags (EST) that show strong similarities to the mammalian protein. We report the identification and cloning of a full-length cDNA clone corresponding to a plant homologue (OsNramp1) of mammalian Nramp. Predicted amino acid sequence of the plant protein indicates a remarkable degree of similarity (60% homology) with its mammalian counterpart, including identical number, position, and composition of transmembrane domains, glycosylation signals, and consensus transport motif, suggesting an identical overall secondary structure and membrane organization for the two proteins. This high degree of structural similarity indicates that the two proteins may be functionally related, possibly through a common mechanism of transport. RNA hybridization studies and RT-PCR analyses indicate that OsNramp1 mRNA is expressed primarily in roots and only at very low levels in leaves/stem. DNA hybridization studies indicate that OsNramp1 is not a single gene, but rather forms part of a novel gene family which has several members in all plants tested including cereals such as rice, wheat, and corn, and also in common weed species. The striking degree of conservation between the macrophage-specific mammalian Nramp and its OsNramp1 plant homologue is discussed with respect to possible implications in the metabolism of nitrate in both organisms.

Amino Acid Sequence↗
PubMed1995

Cardiac disease and nonorganic chest pain: factors leading to disability.

Research has shown that many chest pain patients, without coronary artery disease, may suffer from panic disorder, hypochondriasis, depression, and/or multiple phobias. Some patients with coronary artery disease may also suffer from these disorders and are often unable to return to previous activity. In spite of good prognosis for longevity and acceptable exercise test results, a large proportion of these patients continue to be disabled by chest pain and/or chronic cardiac fears and demand constant medical attention. This study examined the psychiatric and behavioral symptomatology that differentiated four groups of patients experiencing chest pain: the able (active/working patient) with and without coronary artery disease, as determined by exercise thallium-201 studies, and the disabled (inactive/nonworking patient) with and without coronary artery disease. The results of the study indicated that the inactive patients, both with and without heart disease, suffered from a host of debilitating psychiatric conditions.

Aged↗
PubMed1995

Pseudo-alternans of left ventricular end diastolic pressure. A case report.

The authors report a case of left ventricular end diastolic pressure alternans without systolic alternans in a patient with bradycardia and tachypnea. This is an artifact due to the heart rate falling in a 2:1 ratio to the respiratory cycle. Alternation of left ventricular end diastolic pressure should be interpreted carefully in patients with bradycardia.

Artifacts↗