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Dissipation is vital to any cyclic process in realistic systems. Recent research focus on nonequilibrium processes in stochastic systems has revealed a fundamental trade-off, called dissipation-time uncertainty relation, that entropy production rate associated with dissipation bounds the evolution pace of physical processes [Phys. Rev. Lett. 125, 120604 (2020)PRLTAO0031-900710.1103/PhysRevLett.125.120604]. Following the dissipative two-level model exemplified in the same Letter, we experimentally verify this fundamental trade-off in a single trapped ultracold ^{40}Ca^{+} ion using elaborately designed dissipative channels, along with a postprocessing method developed in the data analysis, to build the effective nonequilibrium stochastic evolutions for the energy transfer between two heat baths mediated by a qubit. Since the dissipation-time uncertainty relation imposes a constraint on the quantum speed regarding entropy flux, our observation provides the first experimental evidence confirming such a speed restriction from thermodynamics on quantum operations due to dissipation, which helps us further understand the role of thermodynamical characteristics played in quantum information processing.
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We propose a mechanism of Rydberg double antiblockade by virtue of a resonant dipole-dipole interaction between a pair of Rydberg atoms placed at short distances scaling as 1/R3. By combining this novel excitation regime with microwave-driven fields and dissipative dynamics, a stationary qutrit entangled state can be obtained with high quality, the corresponding steady-state fidelity and purity are insensitive to the variations of the dynamical parameters. Furthermore, we introduce time-dependent laser fields with periodically modulated amplitude to speed up the entanglement creation process. Numerical simulations reveal that the order of magnitude of the shortened convergence time is about 103 in units of ω0, and the acceleration effect appears valid in broad parametric space. The present results enrich the physics of the Rydberg antiblockade regimes and may receive more attention for the experimental investigations in dissipative dynamics of neutral atoms.
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We propose a scheme for quantum geometric computation on a fiber-cavity-fiber system, in which two atoms are located in two single-mode cavities, respectively, connected with each other by optical fiber. This scheme not only has the feature of virtual excitation of photons in the cavity quantum electrodynamics (CQED) that can reduce the effect of decay effectively but also has the advantage of geometric phase to withstand noises due to its built-in noise-resilience feature and robust merit. Specifically, our proposal combined with optimized-control-technology (OCT) can reduce gate operation error by adjusting the time-dependent amplitude and phase of the resonant field which further enhances the robustness of the quantum operation. The robustness against decoherence is demonstrated numerically and the scheme may be applied in the remote quantum information processing tasks and quantum computation.
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Quantum gates induced by geometric phases are intrinsically robust against noise due to the global properties of their evolution paths. Compared to conventional nonadiabatic geometric quantum computation, the recently proposed nonadiabatic noncyclic geometric quantum computation (NNGQC) works in a faster fashion while still remaining the robust feature of the geometric operations. Here, we experimentally implement the NNGQC in a single trapped ultracold ^{40}Ca^{+} ion to verify the noise-resilient and fast feature. By performing unitary operations under imperfect conditions, we witness the advantages of the NNGQC with measured fidelities by quantum process tomography in comparison to other two quantum gates by conventional nonadiabatic geometric quantum computation and by straightforward dynamical evolution. Our results provide the first evidence confirming the possibility of accelerated quantum information processing with limited systematic errors even in an imperfect situation.
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Objective: To describe the confirmation process and long-term follow-up results of 1 case of HIV with long term progression. Methods: The subject was a HIV infected man aged 27 years old. The first HIV antibody positive was detected by ELISA in August 7(th), 2013. Close contacts were identified as 3 homosexual partners who had been contacted before infection and the first sexual partner had been unable to get in touch. Adopting the first epidemiological survey questionnaire of AIDS comprehensive prevention and control information system in China, the investigators conducted face-to-face surveys on the general demographic characteristics and behavioral characteristics of the subject. After the first ELISA test result was positive, 4 rapid detections of colloid selenium, ELISA, western-blot, CD4(+)T and viral load test were followed up (August 14(th), 21(st), 30(th) and September 16(th), 2013). Long term follow-up was performed to detect CD4(+)T and viral load to observe the progress of the case after the diagnosis of infection. Results: The duration of sexual behavior was from 2011 to 2012 between the subject and his 1(st) sexual partner. During the study, repeated HIV antibody ELISA test results were negative. Sexual behavior maintained from January to April 2013 between the subject and his 2(nd) partner and the last one unprotected homosexual acts took place in April 2013. After the traceability survey, the 2(nd) sexual partner was an AIDS patient who had antiretroviral therapy in the anti HIV treatment module of AIDS comprehensive prevention information system. The subject and his 3(rd) partner maintained their sexual behavior from May to October 2013. The two ELISA tests of the 3(rd) partner were negative. Because of the need for hospital operation in August 7, 2013, the subject was tested for HIV antibody by ELISA and the result was positive while western blot test showed that the HIV-1 antibody was not confirmed (band type was gp160/gp120/p24). In the subsequent follow-up, 4 rapid detections of colloid selenium, ELISA and western-blot were conducted and all the results were positive (western-blot band type was gp160/gp120/gp41/p24/p17). Results of continuous follow-up for 5 years showed that the first four CD4(+)T cell counts were as follows: 520, 616, 834, 879. The following 22 CD4(+)T counts sustained at a high level and the median was 895 cells/µl. A total of 5 follow-up visits were conducted to detect viral load exceeding 1 000 copies/ml and the remaining 19 test results were lower than 1 000 copies/ml except that no viral load was detected in 2 follow-up visits. The result of homology analysis showed that the HIV types of the case and its 2(nd) sexual partner were all HIV-1 CRF_01AE. The similarity of gag region gene was 97.5%. So we inferred that the 2(nd) sexual partner was its source of infection, and the case was infected at the end of April 2013 with the last unprotected homosexual behavior. Conclusion: The infected person was found to be an early HIV infection. Continuous follow-up test results indicated that the case belonged to a HIV long-term nonprogressor.
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Infecciones por VIH/diagnóstico , Adulto , Recuento de Linfocito CD4 , China , Estudios de Seguimiento , Infecciones por VIH/inmunología , Humanos , Masculino , Carga ViralRESUMEN
Objective: To survey the prevalence of drug resistant HIV-1 in Shandong province in 2013-2015. Methods: WHO truncated sequential sampling technique was adopted by using 77 and 53 samples of newly diagnosed as HIV-1 positive and aged 16-25 years in Shandong province in 2013 and 2015. RNA was prepared and HIV-1 pol region was amplified by RT-PCR and nested PCR. Pol genetic mutation associated with drug resistance was analyzed. Results: The success rates for sequence acquisition of the survey were 100% (77/77) and 94% (50/53) in 2013 and 2015, and the main subtype was CRF01_AE. A total of 2 surveillance drug-resistance mutation(SDRMs) and 3 SDRMs were found by analyzing the 47 sequences each year, sampled in 2013 and 2015, indicating that the prevalence of drug resistant HIV-1 stains was low in 2013, and moderate in 2015. A total of 5 individuals with drug resistant HIV-1 stains found in this study were mainly infected by homosexual transmission (3 cases), and the other two samples were different: one was infected by heterosexual transmission, the other was infected by IDU. The subtype was CRF01_AE (2 cases) , CRF07_BC (2 cases) and B (1 case) . SDRMs for protease inhibitor (PIs), nucleotide HIV-reverse transcriptase inhibitor (NRTIs) and non-NRTI (NNRTIs) were all found in the individuals with drug resistant HIV-1 stains. Conclusion: CRF01_AE were the main HIV-1 subtypes of recently reported HIV-infected individuals in Shandong province, and the HIV-1 drug resistant strains transmission was catalogued as at low and moderate prevalence level in 2013 and 2015.
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Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genética , Adolescente , Adulto , Femenino , Genes pol , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , VIH-1/genética , Humanos , Masculino , Mutación , Reacción en Cadena de la Polimerasa , Prevalencia , ARN Viral/sangre , ARN Viral/genética , Inhibidores de la Transcriptasa Inversa/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Objective: To analyze the prevalence of HIV, syphilis and related factors among female drug users in Shandong women's compulsory drug rehabilitation center(SWCDRC). Methods: During May 2015, we used a cluster sampling method for drug users in SWCDRC, with a questionnaire and serological testing. We included respondents who volunteered to take part in this study, had clear histories of drug abuse, and had no symptoms of psychosis or current drug use; 451 women participated. The questionnaire addressed socio-demographic information and the participants' health knowledge, including AIDS knowledge, behavioral information, drug use, and STD treatment. We also drew 5 ml blood from each subject for serological tests of HIV and syphilis. Chi-square test was used to compare syphilis antibody positive rate among drug users who had different characteristics. Multi-factor unconditioned logistic regression model was used to explore related factors about syphilis infection of women drug users. Results: Subjects' mean age was(27.25±7.06)years. Of the 451 women, 33.5%(151/451)tested positive for syphilis and 2.2%(10/451)for HIV. The rate of syphilis antibody(SAb)positive whether providing commercial server, providing: 47.2%(25/53); no providing: 31.6%(125/396); χ2=5.12, P=0.024. The SAb + rate from whether having temporary sexual behavior, having: 47.4%(91/192); no having: 23.6%(60/254); χ2=27.6, P<0.001. The SAb+ rate of subjects who tested positive for herpes simplex virus-2(HSV-2)was 39.4%(128/325); for those who tested negative it was 18.3%(23/126); χ2=18.2, P<0.001. The SAb+ rate by frequency of drug use was ≥3 times a week: 36.9%(106/287);<3 times per week: 27.3%(42/154); χ2=4.20, P=0.041. Compared with subjects who were unmarried, divorced, or widowed drug users, the OR(95% CI)for SAb+ among subjects who cohabited with a partner was 2.19(1.36- 3.51). Compared with subjects who had not been having temporary sexual behavior, the OR(95%CI)for SAb+ among subjects who had been having temporary sexual behavior was 2.59(1.65-4.05). Compared with HSV-2- subjects, the OR(95%CI)for SAb+ among subjects who were HSV-2+ was 2.69(1.57-4.59). Conclusion: HIV and syphilis infection rate among female drug users in SWCDRC were significantly higher than in the general population. Subjects who had provided commercial server in the previous 12 months, had temporary sexual behavior in the previous 12 months, were HSV-2+, used drugs ≥3 times per week or cohabitated with a partner had higher syphilis prevalence.
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Consumidores de Drogas , Infecciones por VIH/epidemiología , Parejas Sexuales , Sífilis/epidemiología , Adulto , Femenino , Herpesvirus Humano 2 , Humanos , Prevalencia , Factores de Riesgo , Conducta Sexual , Factores Socioeconómicos , Centros de Tratamiento de Abuso de Sustancias , Trastornos Relacionados con Sustancias/rehabilitación , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Recent studies have revealed that the inflammatory process plays a role in the pathogenesis of osteoarthritis (OA). The S100 family and receptor for advanced glycation end products (RAGE) participate in regulating inflammation, even in the production of matrix metalloproteinases (MMPs). MMP-1 degrades cartilage, which may result in OA development. Moreover, polymorphisms in RAGE, S100A8, and MMP-1 have a marked effect on ligand binding and transcription regulating. In this study, we investigated the potential genetic contribution of the RAGE, S100A8, and MMP-1 genes to OA. We performed a matched case-control association study and genotyped OA patients and healthy controls, who were analyzed by polymerase chain reaction-restriction fragment length polymorphism assays. A total of 207 patients were diagnosed with knee OA and underwent total knee replacement. The control group included 207 individuals who had standard X-rays of the knee joints to confirm K/L < 2 and were matched by age and gender. Single-nucleotide polymorphisms in RAGE (-429T/C, -374T/A, and 557G/A), S100A8 (rs3795391A/G), and MMP-1 (-1607 1G/2G, -755G/T, and -519A/G) were evaluated. RAGE -374T/A, S100A8 rs3795391A/G, MMP-1 -1607 1G/2G, -755G/T, and -519A/G showed no significant difference between OA patients and healthy controls. RAGE -429T/C and 557G/A showed a significant association between OA patients and healthy controls (P = 0.016 and 0.047, respectively). In haplotype analyses, no RAGE and MMP-1 haplotypes showed associations with OA. Our results suggest that the investigated polymorphism in the RAGE gene play a role in OA in the Han Chinese population.
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Pueblo Asiatico/genética , Etnicidad/genética , Predisposición Genética a la Enfermedad , Osteoartritis de la Rodilla/genética , Polimorfismo de Nucleótido Simple/genética , Receptor para Productos Finales de Glicación Avanzada/genética , Índice de Severidad de la Enfermedad , Anciano , Calgranulina A/genética , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Haplotipos/genética , Humanos , Masculino , Metaloproteinasa 1 de la Matriz/genéticaRESUMEN
Objectives: To investigate the potential classification of quality of life in HIV-infected men who have sex with men (HIV-infected MSM) and to analyze possible influencing factors of different categories. Methods: A questionnaire survey was conducted among HIV-infected MSM who received antiretroviral treatment (ART) in an infectious disease hospital in Ji'nan, Shandong Province from October to December 2020. The quality of life scores in six domains were analyzed by latent profile analysis (LPA), and possible related factors of potential classification were explored by ordinal logistic regression analysis. Results: A total of 584 HIV-infected MSM were included in this study. LPA divided their quality of life into three categories, named low score, medium score and high score groups, accounting for 34.4% (201/584), 49.8% (291/584), and 15.8% (92/584), respectively. Multivariate ordinal logistic regression analysis showed that age above 40 years (aOR=1.77, 95%CI:1.11-2.80), monthly average income of 3 000 Yuan and below (aOR=3.15, 95%CI:1.72-5.76), monthly average income of 3 001-5 000 Yuan (aOR=2.26, 95%CI:1.41-3.62), distance to the hospital to receive drugs farer than 40 kms (aOR=1.76, 95%CI:1.07-2.89), and adverse reactions after taking drugs (aOR=2.31, 95%CI:1.65-3.23) were factors associated with low level of quality of life. Conclusions: The qualities of life of HIV-infected MSM showed group heterogeneity and were at high levels. Attention should be focused on HIV-infected MSM who are at older age, with low income, and long distance to access the health facilities. The measures should be taken to reduce the adverse reactions of ART drugs and improve the quality of life.
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Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Humanos , Adulto , Calidad de Vida , Homosexualidad Masculina , Antirretrovirales , Infecciones por VIH/tratamiento farmacológicoRESUMEN
A quantum thermal machine is an open quantum system coupled to hot and cold thermal baths. Thus, its dynamics can be well understood using the concepts and tools from non-Hermitian quantum systems. A hallmark of non-Hermiticity is the existence of exceptional points where the eigenvalues of a non-Hermitian Hamiltonian or a Liouvillian superoperator and their associated eigenvectors coalesce. Here, we report the experimental realization of a single-ion heat engine and demonstrate the effect of Liouvillian exceptional points on the dynamics and the performance of a quantum heat engine. Our experiments have revealed that operating the engine in the exact- and broken-phases, separated by a Liouvillian exceptional point, respectively during the isochoric heating and cooling strokes of an Otto cycle produces more work and output power and achieves higher efficiency than executing the Otto cycle completely in the exact phase where the system has an oscillatory dynamics and higher coherence. This result opens interesting possibilities for the control of quantum heat engines and will be of interest to other research areas that are concerned with the role of coherence and exceptional points in quantum processes and in work extraction by thermal machines.
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BACKGROUND: previous studies examining the contributions of fasting glucose (FG) and postprandial glucose (PPG) to glycated haemoglobin (HbA(1c)) have yielded conflicting results. We aimed to clarify the contributions of PPG to hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring. METHODS: continuous glucose monitoring was conducted in 121 non-insulin-using type 2 diabetic outpatients, who were divided into five groups according to quintiles of HbA(1c) (ranging from 5.7 to 12.7%). Glucose area under the curve (AUC) above a glucose value of 5.5 mmol/L 24 or 4 h after meals was defined as AUC(total). Glucose AUC above FG or preprandial glucose levels was defined as AUC(PPG). The contribution of PPG to hyperglycaemia was calculated as (AUC(PPG)/AUC(total) × 100%. The contribution of FG or preprandial glucose was calculated as [(AUC(total) - AUC(PPG))/AUC(total)] × 100%. RESULTS: the contribution of PPG to either 24-h hyperglycaemia or 4-h hyperglycaemia after meals was significantly higher than FG and preprandial glucose in the lowest quintile of HbA(1c) (both p < 0.001). However, no difference was observed in the other four quintiles. Peak PPG and glucose excursions were higher after breakfast than those after lunch and dinner (p < 0.01 for all comparisons). CONCLUSIONS: in Asian patients with type 2 diabetes, PPG 24 and 4 h after meals was a predominant contributor to excess hyperglycaemia in well-controlled patients and was equally important as FG or preprandial glucose in moderately to poorly controlled patients with mean HbA(1c) up to 10%.
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Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucosa/metabolismo , Hemoglobina Glucada/metabolismo , Hiperglucemia/metabolismo , Periodo Posprandial/fisiología , Adulto , Anciano , Pueblo Asiatico , Ayuno , Femenino , Humanos , Hiperglucemia/etiología , Masculino , Persona de Mediana EdadRESUMEN
Luteoloside (luteolin-7-O-glucoside), the biomarker of Lonicera japonica, was efficiently bio-synthetized from its cheaper precursor luteolin. The structure of luteoloside was characterized by LC-MS and NMR analyses. Compared to the significant inhibitory effect of luteolin on human hepatocyte cell line LO2 at high doses, luteoloside did not show obvious cytotoxic effects at any test dose. Moreover, luteoloside exhibited obvious promotive effects on human hepatocyte cells, suggesting a potential application in hepatoprotective therapies.
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Bacterias/metabolismo , Flavobacteriaceae/química , Flavonas/aislamiento & purificación , Glucósidos/aislamiento & purificación , Lonicera/química , Luteolina/aislamiento & purificación , Rizosfera , Línea Celular , Flavobacteriaceae/metabolismo , Flavonas/química , Glucósidos/biosíntesis , Glucósidos/química , Glucósidos/farmacología , Humanos , Lonicera/microbiología , Luteolina/biosíntesis , Luteolina/química , Luteolina/farmacología , Estructura Molecular , Sustancias ProtectorasRESUMEN
The aim of this study was to assess the efficacy and safety of strontium ranelate in the treatment of postmenopausal women with osteoporosis in Taiwan. In this 12-month multicenter, randomized, double-blind, placebo-controlled study, 125 women with osteoporosis were randomly given either strontium ranelate 2 g daily or placebo. Lumbar spine, femoral neck, and total-hip bone mineral density (BMD) and biochemical markers of bone turnover were measured; adverse events and tolerability were recorded and assessed. Subjects treated with strontium ranelate showed significant increases in BMD of 5.9% at the lumbar spine, 2.6% at the femoral neck, and 2.7% at the total hip, while the placebo group exhibited no significant change at 12 months. Serum level of a formation marker (bone-specific alkaline phosphatase) was also significantly increased at 6 and 12 months. Thus, although the sample size and the treatment duration of this study could not show its effect of reducing osteoprotic fractures, strontium ranelate showed bone protection effects by increasing BMD and concentrations of a bone formation marker. Safety assessment revealed adverse events were mild and not significantly different from placebo.
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Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Calcio/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Tiofenos/uso terapéutico , Vitamina D/uso terapéutico , Anciano , Biomarcadores/sangre , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Calcio/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/efectos adversos , Taiwán , Tiofenos/administración & dosificación , Tiofenos/efectos adversos , Vitamina D/administración & dosificaciónRESUMEN
Monoclonal antibody HBA71 detects a cell surface antigen of human Ewing's sarcomas and peripheral neuroepitheliomas that distinguishes these tumors from other small round cell tumors of childhood and adolescence. In the present study, we show that monoclonal antibody HBA71 reacts with polypeptides of Mr 32,000 and 30,000 and that the HBA71-coding gene segregates with human chromosomes X and Y in rodent-human hybrids. Therefore, we compared HBA71 to the T-cell leukemia antigen 12E7, which is encoded by the pseudoautosomal region of chromosomes X and Y. We show that monoclonal antibodies HBA71 and 12E7 (a) detect polypeptides of identical size, (b) react with mouse cells transfected with complementary DNA corresponding to the 12E7-coding gene, MIC2, and (c) give similar patterns of reactivity with human tumor cell lines and small round cell tumor tissues. Thus, HBA71 and 12E7 are identical or closely related antigens and the available MIC2 probes will facilitate analysis of the molecular mechanisms that determine differential HBA71 expression in small round cell tumors of childhood and adolescence.
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Antígenos CD , Antígenos de Neoplasias/química , Sarcoma de Ewing/inmunología , Antígeno 12E7 , Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/genética , Antígenos de Superficie/inmunología , Western Blotting , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/inmunología , Humanos , Técnicas para Inmunoenzimas , Peso Molecular , Neuroblastoma/inmunología , Sarcoma de Ewing/química , Sarcoma de Ewing/genética , Transfección , Células Tumorales Cultivadas/inmunologíaRESUMEN
We examined expression of prostate-specific membrane antigen (PSM) mRNA in normal prostate using reverse transcription-PCR and sequencing. An alternatively spliced variant, PSM', along with the previously described PSM form, was found in normal prostate. PSM' cDNA is shorter (2387 nucleotides) than PSM (2653 nucleotides). The cDNAs are identical except for a 266-nucleotide region near the 5' end of PSM cDNA (nucleotide 114-380) that is absent from PSM'. This deleted region includes the translation initiation codon and codons for the putative transmembrane domain of PSM. Thus, PSM' RNA codes for a protein that has no apparent signal sequence. We verified the existence of spliced mRNA variants in human primary tissue specimens by RNase protection assay. In LNCaP human prostatic cancer cells and in primary prostate tumors, PSM is the dominant form. In contrast, normal human prostate expressed more PSM' than PSM. Benign prostatic hypertrophy samples showed about equal expression of both variants. We quantified the relative expression of each variant by densitometry and compiled a tumor index, which is the ratio of PSM:PSM' level. LNCaP has an index ranging from 9-11, carcinoma of the prostate from 3-6, benign prostatic hypertrophy from 0.75-1.6, and normal prostate from 0.075-0.45. The index reflects the increased expression of PSM over PSM' following the progression from normal to tumor state. This tumor index may be a useful indicator for the measurement of tumor progression. PSM and PSM' may be functionally different proteins as a result of differences in structure or cellular location. We are investigating the prevalence of one form over the other and how it may influence tumor progression.
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Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Neoplasias de la Próstata/química , ARN Mensajero/análisis , Empalme Alternativo , Secuencia de Aminoácidos , Secuencia de Bases , Glutamato Carboxipeptidasa II , Humanos , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Próstata/química , Células Tumorales CultivadasRESUMEN
The human fibroblast activation protein (FAP), defined by monoclonal antibody F19, is expressed in vivo in reactive stromal fibroblasts of epithelial cancers, subsets of bone and soft tissue sarcomas, and granulation tissue of healing wounds. FAP is generally absent from the stroma of benign epithelial tumors and normal adult tissues. In vitro FAP induction is observed in proliferating cultured fibroblasts and in melanocytes grown with fibroblast growth factor and phorbol ester. In the present study, we show that fibroblast and melanocyte FAP is a cell surface protein comprising noncovalently linked M(r) 95,000 (p95) and M(r) 105,000 (p105) subunits. In contrast, cultured sarcoma and melanoma cell lines express only p95 or are FAP negative. Immunoblot experiments show that p95, but not p105, carries the epitope defined by monoclonal antibody F19. Furthermore, peptide maps of purified p95 and p105 differ, suggesting that they may be distinct gene products. Loss of FAP or a change from p95/p105 to p95 expression accompanies the acquisition of growth factor independence and tumorigenicity in several in vitro test systems, including simian virus 40 transformation of normal fibroblasts, Ha-ras transformation of normal melanocytes, supertransformation of osteosarcoma cells, and enhanced N-MYC expression in variant neuroblastoma cells, whereas serum-starved normal fibroblasts continue to express p95/p105. Thus, fAP expression appears to be linked to the growth factor-dependent proliferative capacity of normal cells and is not merely a secondary event in proliferating cells; furthermore, FAP expression is inversely correlated with growth factor independence and tumorigenicity in transformed cell lines. This distribution pattern is consistent with a role for p95/p105 in mediating extrinsic, growth regulatory signals in normal cells, possibly as a heteromeric cell surface receptor. Such a physiological function may be obviated when oncogenes with cytoplasmic or nuclear sites of action are activated, reducing extrinsic growth factor dependence and permitting down-regulation of FAP in certain transformed cells.
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Antígenos de Neoplasias , Biomarcadores de Tumor , Fibroblastos/química , Sustancias de Crecimiento/análisis , Serina Endopeptidasas , Mama/química , Neoplasias de la Mama/química , Transformación Celular Viral , Células Cultivadas , Endopeptidasas , Femenino , Gelatinasas , Sustancias de Crecimiento/química , Sustancias de Crecimiento/inmunología , Humanos , Melanocitos/química , Proteínas de la Membrana , Peso Molecular , Neuroblastoma/química , Sarcoma/química , Virus 40 de los SimiosRESUMEN
A highly sensitive nested reverse transcriptase-PCR assay, with primers derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) cDNA sequences, has been used to detect occult hematogenous micrometastatic prostate cells. In 77 patients with prostate cancer, PSM and PSA primers detected circulating prostate cells in 48 (62.3%) and 7 (9.1%) patients, respectively. In treated stage D disease patients, PSM primers detected cells in 16 of 24 patients (66.7%), while PSA primers detected cells in 6 of 24 (25%). In post-radical prostectomy patients with negative serum PSA values, PSM primers detected metastases in 21 of 31 patients (67.7%), whereas PSA primers detected cells in only 1 of 33 (3.0%), indicating that micrometastatic spread may be a relatively early event in prostate cancer. The analysis of 40 individuals without known prostate cancer provides evidence that this assay is highly specific and suggests that PSM expression may predict the development of cancer in patients without clinically apparent prostate cancer. Using PSM primers, we detected micrometastases in 4 of 40 controls, 2 of whom had known benign prostatic hyperplasia and were later found to have previously undetected prostate cancer. The clinical significance of detection of hematogenous micrometastic prostate cells using PSM primers and potential applications of this molecular assay, as well as the assay for PSA, merit further study.
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Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/diagnóstico , Secuencia de Bases , Glutamato Carboxipeptidasa II , Humanos , Masculino , Datos de Secuencia Molecular , Metástasis de la Neoplasia , Reacción en Cadena de la Polimerasa , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Sensibilidad y EspecificidadRESUMEN
AIM: This study aimed to determine the contributions of basal excess glycaemia (BEG) and prandial excess glycaemia (PEG) to overall excess glycaemia in type 2 diabetes (T2D) patients treated with metformin alone. METHODS: Outpatients with T2D treated with metformin alone (n=46) who underwent continuous glucose monitoring (CGM) were divided into tertiles according to glycated haemoglobin (HbA1c) levels. For each CGM trace, the glucose area under the curve (AUC)>5.5mmol/L was expressed as the AUCoverall, representing overall excess glycaemia. The sum of glucose AUCs above the premeal glucose level at 4h after breakfast, lunch and dinner was expressed as the AUCpeg, representing PEG. The contribution of PEG to overall excess glycaemia was calculated as (AUCpeg/AUCoverall)×100%. The contribution of BEG was calculated as [(AUCoverall-AUCpeg)/AUCoverall]×100%. Factors related to PEG contribution were also analysed. RESULTS: BEG constituted more than half the overall excess glycaemia in all HbA1c tertiles. The contribution of PEG was negatively correlated with HbA1c and mean glucose values before each meal. Prebreakfast and predinner glucose values were the dominant factors affecting PEG contribution and was independent of HbA1c. CONCLUSION: In patients treated with metformin alone, BEG was the major contributor to excess glycaemia at HbA1c levels ≥7.7%, while PEG and BEG contributions were similar and stable below this level. For HbA1c levels ≥7.7%, add-on therapy to metformin should preferentially target control of BEG, whereas targeting both BEG and PEG could be of equivalent importance with lower HbA1c levels.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Monitoreo Fisiológico/métodos , Adulto , Anciano , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Masculino , Comidas , Persona de Mediana EdadRESUMEN
Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane protein with folate hydrolase and NAALAdase activity. PSMA is highly expressed in prostate cancer and the vasculature of most solid tumors, and is currently the target of a number of diagnostic and therapeutic strategies. PSMA is also expressed in the brain, and is involved in conversion of the major neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glutamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and schizophrenia. To facilitate analysis of the role of PSMA in carcinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 nt portion of the 5' region of the PSMA gene was able to drive the firefly luciferase reporter gene in prostate but not breast-derived cell lines. We have mapped the gene encoding PSMA to 11p11-p12, however a gene homologous, but not identical, to PSMA exists on chromosome 11q14. Analysis of sequence differences between non-coding regions of the two genes suggests duplication and divergence occurred 22 million years ago.
Asunto(s)
Antígenos de Superficie , Carboxipeptidasas/genética , Bacteriófago P1/genética , Secuencia de Bases , Línea Celular , Mapeo Cromosómico , Clonación Molecular , Codón Iniciador , Duplicación de Gen , Glutamato Carboxipeptidasa II , Humanos , Datos de Secuencia Molecular , Regiones Promotoras GenéticasRESUMEN
OBJECTIVE: An on-going study at the Memorial Sloan-Kettering Cancer Center assessed the effectiveness of androgen deprivation therapy (ADT) prior to surgical removal of the prostate. In this report, we evaluate the effectiveness of ADT on systemic disease by monitoring the presence or absence of circulating prostatic epithelial cells using a reverse transcription polymerase chain reaction (RT-PCR) assay for prostatic-specific membrane antigen (PSM). METHODS: PSM RT-PCR was performed on a total of 38 prostate cancer patients. There were 12 pT2 patients in the ADT group and 10 patients in the control pT2 group and 5 pT3 patients in the ADT group and 11 pT3 patients in the control group. RESULTS: For pT2 patients, 2 of the 12 patients (17%) were positive for circulating prostatic cells during androgen deprivation therapy but before radical retroprostatectomy (RRP). Within a 6-month period after RRP, 3 of 12 patients (25%) were positive. For the period between the 7th and 12th month after RRP, 6 of 12 patients (50%) were positive. For the period 12-36 months after RRP, 2 of the 12 patients (17%) remained positive for circulating prostatic cells. In contrast, the pT2 control group had higher positive rates in comparable periods: 4 of 10 patients (40%) were positive prior to surgery; 6 of 10 patients (60%) were positive during the 6 months following surgery. For the period between the 7th and 12th month following surgery, 4 of 7 patients (57%) were positive for PSM. Finally, 3 of 6 patients (50%) were positive for the period longer than 12 months. Regarding patients who have extraprostatic disease (stage pT3), the ADT group had a lower rate of circulating PSM positive cells. Before RRP and during androgen deprivation therapy, 1 out of 5 patients (20%) in the ADT group were positive as compared to 4 out of 11 patients for the control group. Within a 6-month period after RRP, the ADT group had 4 out of 9 (44%) patients positive for PSM as compared to 9 of 11 (82%) for the control group. For the period between the 7th and 12th months postsurgery, 1 of 5 patients (20%) of the ADT group were positive as compared to 4 of 7 (57%) of the control patients. CONCLUSIONS: These results indicate that patients with pT2 and pT3 lesions who receive neoadjuvant ADT are less likely to have circulating tumor cells detected compared to a control group both prior to and after surgery. In addition, irrespective of ADT or control group, there were increases in the detection of circulating tumor cells in the period after RRP, and this rise gradually decreased, suggesting that surgical manipulation may cause hematogenous dissemination of tumor cells and that ADT reduces such dissemination of tumor cells. Overall, these results indicate that the use of neoadjuvant ADT decreases the number of circulating prostatic cells. These data represent the initial results of an on-going study. As additional patients are added to the studies, attempts to correlate PSM positivity and serum PSA values postoperatively, recurrence, and margin positivity will be made.