Search PubMed⌕ Search

Biomedical subjects

H Zhang

Publications and source records attributed to H Zhang.

At least 145 records · Page 8Linked to original sources
PubMed2003

A consolidated linkage map for rainbow trout (Oncorhynchus mykiss).

Androgenetic doubled haploid progeny produced from a cross between the Oregon State University and Arlee clonal rainbow trout (Oncorhynchus mykiss) lines, used for a previous published rainbow trout map, were used to update the map with the addition of more amplified fragment length polymorphic (AFLP) markers, microsatellites, type I and allozyme markers. We have added more than 900 markers, bringing the total number to 1359 genetic markers and the sex phenotype including 799 EcoRI AFLPs, 174 PstI AFLPs, 226 microsatellites, 72 VNTR, 38 SINE markers, 29 known genes, 12 minisatellites, five RAPDs, and four allozymes. Thirty major linkage groups were identified. Synteny of linkage groups in our map with the outcrossed microsatellite map has been established for all except one linkage group in this doubled haploid cross. Putative homeologous relationships among linkage groups, resulting from the autotetraploid nature of the salmonid genome, have been revealed based on the placement of duplicated microsatellites and type I loci.

Animals↗
PubMed2003

Protein kinase and protein phosphatase expression in amyotrophic lateral sclerosis spinal cord.

The Kinetworks trade mark multi-immunoblotting technique was used to evaluate the expressions of 78 protein kinases, 24 protein phosphatases and phosphorylation states of 31 phosphoproteins in thoracic spinal cord tissue from control subjects and patients having the sporadic form of amyotrophic lateral sclerosis (ALS). In both the cytosolic (C) and particulate (P) fractions of spinal cord from ALS patients as compared with controls, there were increased levels of calcium/calmodulin-dependent protein kinase kinase (CaMKK; C = 120% increase/P = 580% increase;% change, compared with control), extracellular regulated kinase 2 (ERK2; C = 120% increase/P = 170% increase), G protein-coupled receptor kinase 2 (GRK2; C = 140% increase/P = 140% increase), phospho-Y279/216 glycogen synthase kinase 3 alpha/beta (GSK3alpha/beta; C = 90% increase/P = 220% increase), protein kinase B alpha (PKBalpha; C = 360% increase/P = 200% increase), phospho-T638 PKCalpha/beta (C = 630% increase/P = 170% increase), cGMP-dependent protein kinase (PKG; C = 100% increase/P = 75% increase), phospho-T451 dsRNA-dependent protein kinase (PKR; C = 2600% increase/P = 3330% increase), ribosomal S6 kinase 1 (RSK1; C = 750% increase/P = 630% increase), phospho-T389 p70 S6 kinase (S6K; C = 1000% increase/P = 460% increase), and protein-tyrosine phosphatase 1 delta (PTP1delta; C = 43% increase/P = 70% increase). Cytosolic increases in phospho-alpha-S724/gamma-S662 adducin (C = 15650% increase), PKCalpha (C = 100% increase) and PKCzeta (C = 190% increase) were found in ALS patients as compared with controls, while particulate increases in cAMP-dependent protein kinase (PKA; 43% increase), protein kinase C beta (PKCbeta; 330% increase), and stress-activated protein kinase beta (SAPKbeta; 34% increase) were also observed. Cyclin-dependent kinase-associated phosphatase (KAP) was apparently translocated, as it was reduced (31% decrease) in cytosolic fractions but elevated (100% increase) in particulate fractions of ALS spinal cord tissue. Our observations indicate that ALS is associated with the elevated expression and/or activation of many protein kinases, including PKCalpha, PKCbeta, PKCzeta and GSK3alpha/beta, which may augment neural death in ALS, and CaMKK, PKBalpha, Rsk1, S6K, and SAPK, which may be a response to neuronal injury that potentially can mitigate cell death.

Aged↗
PubMed2003

All-trans retinoic acid (atRA) differentially induces apoptosis in matched primary and metastatic melanoma cells -- a speculation on damage effect of atRA via mitochondrial dysfunction and cell cycle redistribution.

All-trans retinoic acid (atRA) has been suggested to exert its cytotoxicity via apoptosis but the mechanisms behind the damage effects have not been fully understood. In this study, we investigated the cytotoxic effects of atRA in eleven primary and matched metastatic cutaneous melanoma cell lines. All the primary and metastatic melanoma cell lines examined expressed the retinoic acid receptors. The cultured melanoma cells treated with atRA showed dysfunction of mitochondria and altered cell cycle distribution, inhibited cell proliferation and apoptosis. The cytotoxic effects of atRA were dose- and time-dependent. The dysfunction of mitochondria and induction of apoptosis were more pronounced in the primary tumor cells than in the metastatic cell lines from the same patients. The data indicate that the cytotoxic effect of atRA was mediated through dysfunction of mitochondria, alterations in cell cycle and induction of apoptosis. Melanoma in early stage may have better response to atRA adjuvant therapy than the melanoma in late stage, suggesting the early utility of atRA in melanoma chemotherapy.

Apoptosis↗
PubMed2003

11C-choline PET for the detection of bone and soft tissue tumours in comparison with FDG PET.

We assessed and compared the usefulness of C-choline positron emission tomography (PET) with that of 2-[ F]fluoro-2-deoxy-D-glucose (FDG) PET for the differentiation between benign and malignant bone and soft tissue tumours. A total of 43 patients with 45 lesions were included. C-choline PET and FDG PET were performed from 5 and 40 min, respectively, after injection of 275-370 MBq tracer. PET data were evaluated by using the standardized uptake value (SUV) and were analysed according to the pathological data. C-choline uptake in malignancies was 4.9+/-2.1 (n=14), which was significantly higher than that in benign lesions (2.5+/-1.7, n=31) (P <0.0001). The sensitivity, specificity and accuracy of C-choline PET were 100%, 64.5% and 75.6%, respectively, when 2.59 of the SUV was used as the cut-off value. The FDG uptake in malignancies was 5.1+/-4.2 (n=14) and was also significantly larger than that in benign lesions 2.9+/-2.9 (n=31) (P<0.003). The sensitivity, specificity and accuracy of FDG PET were 85.7%, 41.9% and 55.6%, respectively (cut-off=1.83). The C-choline uptake in the lesions correlated with FDG uptake ( r=0.61, P<0.003). In receiver operating characteristic (ROC) analysis, the area under the ROC curve for C-choline PET (area=0.847) was higher than that for FDG PET (area=0.717). This study showed that C-choline PET was superior to FDG PET in differentiation between malignant and benign lesion in bone and soft tissue tumours. C-choline PET might be useful as a screening method for malignant bone and soft tissue tumours.

Adolescent↗
PubMed2003

A comparative study of 11C-choline PET and [18F]fluorodeoxyglucose PET in the evaluation of lung cancer.

The purpose of this study was to compare the diagnostic value of 11C-choline positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) PET imaging in the detection of primary lung cancer and mediastinal lymph node metastases. Seventeen patients with histologically proven primary lung cancer were examined with both 11C-choline and FDG PET within a week of each study. Lung cancers were analysed visually and semiquantitatively using the ratio of tumour-to-normal radioactivity (T/N ratio) and standardized uptake value (SUV). Mediastinal lymph node metastases were analysed visually. Although both techniques delineated focal lesions with an increase in tracer accumulation in 13 patients, FDG PET identified three additional patients in whom 11C-choline PET did not visualize any lesion. In the detection of lung cancer <2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than 11C-choline PET (four of seven, 57.1%). The T/N ratio and SUV were significantly higher with FDG PET (T/N ratio, 7.43+/-6.22; SUV, 4.05+/-3.05) than these were with 11C-choline PET (T/N ratio, 2.93+/-1.19; SUV, 2.93+/-0.79) (P<0.001). There was a significant positive correlation between the T/N ratios and SUVs of FDG and 11C-choline. In the assessment of mediastinal lymph node involvement, FDG PET detected lymph node metastases in two patients who were negative on 11C-choline PET, whereas both techniques could not detect tumour involvement in one patient. Both techniques have clinical value for the non-invasive detection of primary lung cancer that is 2 cm or greater in size. However, FDG PET is superior to 11C-choline PET in the detection of lung cancer that is less than 2 cm in diameter and in mediastinal lymph node metastases.

Adenocarcinoma↗
PubMed2003

Assessment of myocardial viability with a positron coincidence gamma camera using fluorodeoxyglucose in comparison with dedicated PET.

The use of dual-head gamma camera modified positron coincidence detection (PCD) is a new, alternative method of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) imaging. This study investigated the potential ability of evaluating myocardial viability in patients with ischaemic heart disease by FDG imaging using PCD. A total of 21 patients (18 male, three female; mean age 59.7+/-8.5 years) with a history of previous myocardial infarction and confirmed coronary angiography underwent FDG PCD and FDG PET after oral glucose loading (75 g). Quantitative analysis was compared between images of FDG PCD and FDG PET. A significant linear correlation between the segmental percentage of FDG uptake obtained by PCD and PET was observed (r=0.63, P<0.001). By receiver operating characteristic (ROC) analysis, using FDG PET as the 'gold standard', at the 50% threshold value in PET, FDG PCD showed a sensitivity of 92% and specificity of 63% in detecting myocardial viability. Regional analysis showed lower agreement of FDG PCD and FDG PET in the inferior (79%) and septal (70%) walls compared with the other walls. Quantitative evaluation of myocardial viability using FDG PCD yielded comparable clinical results in apex, anterior and lateral walls to that of FDG PET. However, the agreement was lower in the inferior and septal walls. Therefore, results of FDG PCD should be carefully interpreted in evaluating myocardial viability in the inferior and septal walls. The application of a measured attenuation correction and scatter correction are needed to improve the detectability of myocardial viability in FDG imaging by coincidence gamma camera.

Aged↗
PubMed2003

Enterovirus related metabolic myopathy: a postviral fatigue syndrome.

OBJECTIVE: To detect and characterise enterovirus RNA in skeletal muscle from patients with chronic fatigue syndrome (CFS) and to compare efficiency of muscle energy metabolism in enterovirus positive and negative CFS patients. METHODS: Quadriceps muscle biopsy samples from 48 patients with CFS were processed to detect enterovirus RNA by two stage, reverse transcription, nested polymerase chain reaction (RT-NPCR), using enterovirus group specific primer sets. Direct nucleotide sequencing of PCR products was used to characterise the enterovirus. Controls were 29 subjects with normal muscles. On the day of biopsy, each CFS patient undertook a subanaerobic threshold exercise test (SATET). Venous plasma lactate was measured immediately before and after exercise, and 30 minutes after testing. An abnormal lactate response to exercise (SATET+) was defined as an exercise test in which plasma lactate exceeded the upper 99% confidence limits for normal sedentary controls at two or more time points. RESULTS: Muscle biopsy samples from 20.8% of the CFS patients were positive for enterovirus sequences by RT-NPCR, while all the 29 control samples were negative; 58.3% of the CFS patients had a SATET+ response. Nine of the 10 enterovirus positive cases were among the 28 SATET+ patients (32.1%), compared with only one (5%) of the 20 SATET- patients. PCR products were most closely related to coxsackie B virus. CONCLUSIONS: There is an association between abnormal lactate response to exercise, reflecting impaired muscle energy metabolism, and the presence of enterovirus sequences in muscle in a proportion of CFS patients.

Adult↗
PubMed2003

PET in the follow-up of differentiated thyroid cancer.

Fluorine-18-fluorodeoxyglucose (FDG) PET has become an increasingly important functional imaging modality in clinical oncology. This article will focus primarily on the role of FDG PET during treatment and follow-up of thyroid cancer. The major role of FDG PET is in patients with elevated thyroglobulin (Tg) levels where thyroid cancer tissue does not concentrate radioiodine rendering false-negative results on I-131 scanning. FDG PET imaging takes advantage of the increased uptake of FDG in cancer cells and is sensitive (60-94%) to the detection of recurrent or metastatic cancer in patients who have negative radioiodine scans. The specificity (25-90%) of PET imaging is relatively less than its sensitivity because some inflammatory processes avidly accumulate FDG. PET can fail to localize the tumour sites in some patients with well-differentiated thyroid cancer that retain good iodine ability. This can result the well recognized phenomenon of "flip-flop" depending on the differentiation of the thyroid cancer. Several studies have documented the higher accuracy of PET, compared with other imaging modalities in the evaluation of patients with recurrent or metastatic differentiated thyroid cancer. The value of thyroid stimulating hormone stimulation for FDG PET has recently been reported. Therefore, if available, this method should be considered in all patients of differentiated thyroid cancer with suspected recurrence and/or metastasis.

Fluorodeoxyglucose F18↗
PubMed2003

Effects of projective bone area size of the spine on bone density and the diagnosis of osteoporosis in healthy pre-menopausal women in China.

The aim of this study was to understand the effects of projective bone area (BA) size of the spine on bone density and the diagnosis of osteoporosis. Measurements of BA, bone mineral content (BMC), areal bone density (aBMD) and volumetric bone density (vBMD) at the posteroanterior (PA) lumbar spine (vertebrae L2-L4) followed by a paired PA/lateral spine (L2-L4) were made using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 1436 healthy pre-menopausal women aged from 20 to 56-years-old. At the PA and lateral lumbar spine, there was a significant positive correlation between BA and BMC (r=0.762 and 0.762, p=0.000) and aBMD (r=0.370 and 0.352, p=0.000), but not vBMD (r=0.000 and 0.102, p=0.813 and 0.063). When BA at the PA spine changed by one standard deviation (SD), BMC and aBMD correspondingly changed by 12.6% and 4.3% on the basis of their respective means while vBMD indicated no change. When a variation of 1 SD was observed in BA at the lateral spine, BMC, aBMD and vBMD correspondingly changed by 13.8%, 4.4% and 1.73% on the basis of their respective means. Through an intercomparison among large, intermediate and small BA groups, significant differences were found in the means of subject's height, weight, BMC and aBMD at the PA and lateral spine as well as the detection rate of osteoporosis by aBMD (p=0.000). Detection rates of osteoporosis by aBMD at the PA, lateral spine and vBMD in healthy pre-menopausal women aged from 40 years to 56 years were 4.5%, 16.4% and 9.7%, respectively, in the small BA group; 1.3%, 6.4% and 7.3%, respectively, in the intermediate BA group; and 0, 0 and 5.5%, respectively, in the large BA group. No significant differences were found in the detection rates of osteoporosis by vBMD among the groups. The results of multiple linear regression revealed that the major factors influencing BA of the lumbar spine was height. In healthy pre-menopausal women of the same race and age, the BA size of the lumbar spine would have significant influence upon aBMD and the diagnosis of osteoporosis, i.e. the larger the BA, the greater the aBMD and the lower the osteoporosis detection rate while conversely, the smaller the BA, the smaller the aBMD and the higher the osteoporosis detection rate. Though vBMD does not change with BA sizes of the lumbar spine, it is a sensitive marker for diagnosing osteoporosis.

Absorptiometry, Photon↗
PubMed2003

Age-related variation in quantitative ultrasound at the tibia and prevalence of osteoporosis in native Chinese women.

This study investigated the variations in age-related speed of sound (SOS) at the tibia and prevalence of osteoporosis in native Chinese women, and establishment of a reference database by quantitative ultrasound. SOS at the right midtibia was measured using a quantitative ultrasound device (SoundScan 2000, Myriad Ultrasound Systems, Israel) in 1596 healthy Chinese women ranging from 12 years to 96 years of age. Healthy women were selected on the basis of (1). a detailed questionnaire about their medical history, (2). face to face questioning about their medical history, and (3). a physical examination. Women with a medical condition that required medication that affected bone metabolism or those who had had a pathologic or moderate traumatic fracture were excluded. We followed the diagnostic criteria provided by the instrument's manufacturer and equivalent to the WHO criteria (using the T-score cut-off that diagnoses 30% of the post-menopausal women aged >or =50 years with osteoporosis) as the diagnostic criteria for osteoporosis in this group of women. Data were analyzed in age groups divided by intervals of 5 years. The peak SOS at the tibia of 3991+/-68 m s(-1) (mean+/-SD) occurred in the 35-39 year age group and the T-score precision was 0.99 T-score units. The SOS value increased with age up to 34 years of age and then declined with age after 40 years of age with the rate of decrease at 9.68 m s(-1) per year. The curve representing the SOS change according to age is best fitted by the regression analysis of cubic model, and the cubic equation for SOS=3383+39.9 (age)-0.78 (age)(2)+0.0039 (age)(3) (R(2)=0.505, p=0.000). The T-score cut-off that diagnoses 30% of the post-menopausal women (n=559, mean age 63.2+/-8.97 years) aged >or=50 years with osteoporosis was SOS or=80 years, the prevalences of osteoporosis detected using equivalent to the WHO criteria were 0.39%, 9.27%, 30.3%, 58.4% and 69.0%, respectively. The prevalences detected following the manufacturer's diagnostic criteria (cut-off value: SOS<or=3800 m s(-1), T-score<or=-2.0) were 3.14%, 20.5%, 53.2%, 78.8% and 89.7%, respectively. There were significant differences in the prevalence between the diagnostic criteria in the various age groups (p=0.000-0.002). In 769 women from 40 years to 59 years of age, the mean SOS was significantly higher in pre-menopausal women (n=500) than in post-menopausal women (n=269) (3977+/-89 vs 3881+/-118 m s(-1), p=0.000). The prevalence of osteoporosis in these women was 0.40% in pre-menopausal women, 8.92% in post-menopausal women, respectively. There were significant differences in prevalence of osteoporosis between the two groups of pre- and post-menopausal women (p=0.000). In conclusion, SOS at tibia can provided useful information about bone status in the normative population of native Chinese women for determination of osteoporosis. The reference database based on these data will be appropriate for the diagnosis of osteoporosis by tibial quantitative ultrasound in native Chinese women.

Adolescent↗
PubMed2003

Upregulation of Fas and FasL expression in testosterone-induced apoptosis of macrophages.

To the best of the authors' knowledge, there have been few reports on the effect of testosterone on the apoptosis of macrophages. In this report, we studied the effect of testosterone on the apoptosis of bone marrow-derived macrophages (BMMs) and the function of the Fas/Fas ligand (FasL) system in the process. Results showed that testosterone treatment in vitro at the physiological concentration of 10 nM did not induce the apoptosis of BMMs. However, BMMs underwent apoptosis when treated at higher concentrations of testosterone (100, 200 and 400 nM). Testosterone-induced apoptosis was associated with the enhanced expression of Fas, FasL, and caspase-8. These data suggest that the Fas/FasL system may play an important role in the testosterone-induced apoptosis of macrophages.

Animals↗
PubMed2003

A comparative study of anaerobic digestion of food waste in a single pass, a leachate recycle and coupled solid/liquid reactors.

A single pass reactor (R1), a leachate recycle reactor (R2) and a coupled solid/liquid bioreactor (R3-Rm) for anaerobic digestion of food waste were comparatively investigated in terms of digestion process and treatment efficiency. The coupled solid/liquid bioreactor is an enhanced two-phase system and distinctive from a traditional two-phase process with an upflow anaerobic sludge blanket (UASB) reactor as the methanogenic phase and a circulation of treated leachate between the acidification and methanogenic phases. In comparison with R1 and R2, R3-Rm enhanced the digestion process and increased the methane content of biogas. 100% of the R3-Rm methane yield was from the methanogenic phase with average methane content of 71%. The significant enhancement was also confirmed by the removal of 79% of total organic carbon (TOC), 60% of volatile solids (VS) and 80% of total COD in 12 days running of R3-Rm. However, no active methane fermentation was detected in R1 and R2 during 60 days operation. The results in this laboratory-scale study show that the rapid accumulation of volatile fatty acids (VFAs) due to the rapid acidification of food waste inhibits the development of effective methane fermentation in single pass and leachate recycle reactors. The coupled solid/liquid bioreactor is more efficient in converting food waste into methane and carbon dioxide.

Bacteria, Anaerobic↗
PubMed2003

Antibody like peptidomimetics as large scale immunodetection probes.

Antibodies are often used to study the molecular basis of physiologic processes. Despite the widespread applications of monoclonal antibodies (mAb) from basic science to successful therapeutics in clinical settings their use is limited. Production of mAb is often cumbersome and creating diverse and therapeutic amounts of useful mAb is difficult. We have developed a methodology to reduce an antibody into much smaller peptidomimetics and have engineered the mimetics for increased serum half life and affinity. The novel species are termed "antibody like binding peptidomimetics" (ABiP). We developed the Anti-Her2/neu peptidomimetic (AHNP) which is a mimic of Herceptin, a mAb used for advanced breast cancer therapy. The AHNP has been used as a defining tool to develop immunodetection probes that exemplify a general process application. AHNP has been expressed as an oligomeric fusion protein with streptavidin. These Herceptin like ABiPs were used to detect the Her2/neu antigen at extremely low concentrations using the immunodetection amplification technique (IDAT) which our laboratory has also developed. A fully developed highly diverse library of ABiPs represents an alternative for panels of monoclonal antibodies and may also be useful for target validation, antigen detection, therapeutics and as a platform for drug development.

Animals↗
PubMed2003

Semi-continuous anaerobic digestion of food waste using a hybrid anaerobic solid-liquid bioreactor.

A hybrid anaerobic solid-liquid (HASL) bioreactor was developed to enhance food waste conversion. The HASL bioreactor is a modified two-phase anaerobic digestion system with a solid waste reactor and a high-rate anaerobic wastewater reactor, which was a UASB reactor. In this study, the methanogenesis in the UASB reactor was investigated under a semi-continuous operation of the food waste digestion system. The HASL process, including 7 days of start-up and 23 days of semi-continuous operation followed by 6 days of batch operation, was commenced by loading 2.8 kg of shredded food waste. During the semi-continuous operation, 0.2 kg of the same waste was loaded daily. The leachate from acidification phase, i.e., solid waste reactor, remained acidic (pH 4.9-5.5) and high in total VFA (TVFA), 9,500-11,500 mg/L, and COD (8,000-11,800 mg/L) levels. In the methanogenesis phase, i.e., UASB reactor, effective TVFA and COD removals (88 +/- 5% and 85 +/- 7%, respectively) were obtained, while the methane content was 71%. At the end of operation, about 78% of VS added in the HASL bioreactor was removed, while TOC and total COD reductions were 78% and 79%, respectively. The results showed that the use of UASB reactor in the semi-continuous HASL system can enhance the methanogenesis process and increase the methane content in biogas production.

Bacteria, Anaerobic↗
PubMed2002

Prevention of human immunodeficiency virus-related opportunistic infections in France: a cost-effectiveness analysis.

A simulation model of human immunodeficiency virus (HIV) disease, which incorporated French data on the progression of HIV disease in the absence of antiretroviral therapy and on cost, was used to determine the clinical impact and cost-effectiveness of different strategies for the prevention of opportunistic infections in French patients who receive highly active antiretroviral therapy (HAART). Compared with use of no prophylaxis, use of trimethoprim-sulfamethoxazole (TMP-SMZ) increased per-person lifetime costs from euro 185,600 to euro 187,900 and quality-adjusted life expectancy from 112.2 to 113.7 months, for an incremental cost-effectiveness ratio of euro 18,700 per quality-adjusted life-year (euro/QALY) gained. Compared with use of TMP-SMZ alone, use of TMP-SMZ plus azithromycin cost euro 23,900/QALY gained; adding fluconazole cost an additional euro 54,500/QALY gained. All strategies that included oral ganciclovir had cost-effectiveness ratios that exceeded euro 100,000/QALY gained. In the era of HAART, on the basis of French data, prophylaxis against Pneumocystis carinii pneumonia, toxoplasmic encephalitis, and Mycobacterium avium complex bacteremia is cost-effective. Prophylaxis against fungal and cytomegalovirus infections is less cost-effective than are other therapeutic options for HIV disease and should remain of lower priority.

AIDS-Related Opportunistic Infections↗
PubMed2002

Degradation pathway of the phosphonate ciliatine: crystal structure of 2-aminoethylphosphonate transaminase.

Phosphonates allow certain organisms to thrive in otherwise hostile environments, and 2-aminoethylphosphonate (AEP) is a precursor of many cellular phosphonates. AEP transaminase (AEPT) is an enzyme essential to phosphonate synthesis and degradation pathways. The crystal structure of AEP transaminase was determined by multiwavelength anomalous diffraction of 66 selenium atoms. The refined structure at 2.2 A resolution revealed an overall fold and active site location similar to those of the dimeric, two-domain structure of type I aminotransferases. The active site contains a cofactor, pyridoxal 5'-phosphate (PLP), and the product phosphonoacetaldehyde. Comparison with other type I aminotransferase structures shows that the PLP-protein interactions are conserved. Modeling of bound substrates and products reveals the structural basis for AEP recognition and the stereospecificity of proton elimination at the alpha-carbon and indicates conformational changes along the reaction pathway.

Aminoethylphosphonic Acid↗
PubMed2002

A novel transporter, Pfcrt, confers antimalarial drug resistance.

The elucidation of the molecular details of drug resistance phenomena is a very active area of research that crosses many disciplinary boundaries. Drug resistance is due to altered drug-target interaction, and/or dysregulated signaling related to cell growth and death. Since many drugs need to rapidly diffuse into and within cells in order to find their targets, and since transmembrane ion transport is an important facet of cellular signaling, it is not surprising that membrane transport phenomena have been implicated in the evolution of drug resistance in tumor cells, bacteria, and intracellular parasites such as Plasmodium falciparum, the causative agent of the most lethal form of human malaria. The most infamous membrane transport protein involved in drug resistance is "MDR protein" or "P-glycoprotein" (Pgp),1 which was found to be overexpressed in drug-resistant tumor cells over 15 years ago, and which is representative of the ATP-binding cassette (ABC) superfamily that also includes the important cystic fibrosis transmembrane conductance regulator (CFTR) and sulfonyl urea receptor (SUR) ion channels. Availability of mouse and human Pgp cDNA rather quickly led to the identification of homologues in many species, including P. falciparum, and these were de facto assumed to be the ultimate determinants of drug resistance in these systems as well. However, research over the past 10 years has taught us that this assumption likely is wrong and that the situation is more complex. We now know that human Pgp plays a relatively minor role in clinically relevant tumor drug resistance, and that an integral membrane protein with no homology to the ABC superfamily, Pfcrt, ultimately confers chloroquine resistance in P. falciparum. Thus, the general hypothesis that membrane transport and membrane transport proteins are important in drug resistance phenomena remains correct, but at a genetic, biochemical, and physiological level we have recently witnessed a few very interesting surprises.

Animals↗