RESUMEN
C-arm linacs have been used widely to treat multiple cranial metastases using stereotactic radiosurgery (SRS). A new generation of O-ring linacs offer several workflow advantages when compared to C-arm platforms. However, O-ring linacs are not able to employ couch rotations for noncoplanar beams used in SRS treatments. This study was conducted in order to simulate further possible developments of O-ring treatment units by assessing their geometrical efficiency. In this work we compare the plan quality for C-arm versus an O-ring platform including metrics that are relevant to SRS for multiple metastases. The comparison is conducted by incorporating tilted arcs on the O-ring platform therefore introducing noncoplanarity. Total 40 patients previously treated for SRS with 20 Gy single fraction were replanned for C-arm with a standard noncoplanar 5-arc arrangement and O-ring with both coplanar and noncoplanar beams. For the O-ring plans, we considered a default 3-arc coplanar arrangement, as well as 3- and 5-arc arrangements with arcs tipped up to 10 degrees from the axial plane. Target coverage, organ-at-risk (OAR) doses, monitor unit (MU) efficiency, conformity and gradient indices were assessed for all plans. For most metrics the O-ring geometries, even the coplanar arrangement, produced statistically comparable results to the C-arm. Small but significant differences were found for the 3 arc O-ring for PTV: D90%, D2% and MU/Gy and for the 5 arc O-ring at D2% when both were compared to the C-arm. Cumulative dose volume histograms (DVHs) for normal brain showed a cross-over between the C-arm and coplanar O-ring geometry at a low dose (2.3 ± 1.8 Gy), with O-ring associated with higher volumes above this cross-over dose. However, no statistical difference was seen in the brainstem, optic pathway and volumes of normal brain receiving 12 Gy or 20 Gy. This study has found that O-ring geometry linacs can produce SRS plans of comparable quality to those from a C-arm for multiple cranial metastases.
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Widespread manganese-sensing transcriptional riboswitches effect the dependable gene regulation needed for bacterial manganese homeostasis in changing environments. Riboswitches - like most structured RNAs - are believed to fold co-transcriptionally, subject to both ligand binding and transcription events; yet how these processes are orchestrated for robust regulation is poorly understood. Through a combination of single-molecule and bulk approaches, we discover how a single Mn2+ ion and the transcribing RNA polymerase (RNAP), paused immediately downstream by a DNA template sequence, are coordinated by the bridging switch helix P1.1 in the representative Lactococcus lactis riboswitch. This coordination achieves a heretofore-overlooked semi-docked global conformation of the nascent RNA, P1.1 base pair stabilization, transcription factor NusA ejection, and RNAP pause extension, thereby enforcing transcription readthrough. Our work demonstrates how a central, adaptable RNA helix functions analogous to a molecular fulcrum of a first-class lever system to integrate disparate signals for finely balanced gene expression control.
Asunto(s)
ARN Polimerasas Dirigidas por ADN , Regulación Bacteriana de la Expresión Génica , Lactococcus lactis , Conformación de Ácido Nucleico , ARN Bacteriano , Riboswitch , Transcripción Genética , Riboswitch/genética , Lactococcus lactis/genética , Lactococcus lactis/metabolismo , ARN Polimerasas Dirigidas por ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , ARN Bacteriano/metabolismo , ARN Bacteriano/genética , ARN Bacteriano/química , Manganeso/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Imagen Individual de MoléculaRESUMEN
Understanding complex biological events at the molecular level paves the path to determine mechanistic processes across the timescale necessary for breakthrough discoveries. While various conventional biophysical methods provide some information for understanding biological systems, they often lack a complete picture of the molecular-level details of such dynamic processes. Studies at the single-molecule level have emerged to provide crucial missing links to understanding complex and dynamic pathways in biological systems, which are often superseded by bulk biophysical and biochemical studies. Latest developments in techniques combining single-molecule manipulation tools such as optical tweezers and visualization tools such as fluorescence or label-free microscopy have enabled the investigation of complex and dynamic biomolecular interactions at the single-molecule level. In this review, we present recent advances using correlated single-molecule manipulation and visualization-based approaches to obtain a more advanced understanding of the pathways for fundamental biological processes, and how this combination technique is facilitating research in the dynamic single-molecule (DSM), cell biology, and nanomaterials fields.
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Nanotecnología , Pinzas Ópticas , Microscopía Fluorescente/métodosRESUMEN
Noncoding, structured 5'-untranslated regions (5'-UTRs) of bacterial messenger RNAs (mRNAs) can control translation efficiency by forming structures that either recruit or repel the ribosome. Here we exploit a 5'-UTR embedded preQ1-sensing, pseudoknotted translational riboswitch to probe how binding of a small ligand controls recruitment of the bacterial ribosome to the partially overlapping Shine-Dalgarno (SD) sequence. Combining single-molecule fluorescence microscopy with mutational analyses, we find that the stability of 30S ribosomal subunit binding is inversely correlated with the free energy needed to unfold the 5'-UTR during mRNA accommodation into the mRNA binding cleft. Ligand binding to the riboswitch stabilizes the structure to both antagonize 30S recruitment and accelerate 30S dissociation. Proximity of the 5'-UTR and stability of the SD:anti-SD interaction both play important roles in modulating the initial 30S-mRNA interaction. Finally, depletion of small ribosomal subunit protein S1, known to help resolve structured 5'-UTRs, further increases the energetic penalty for mRNA accommodation. The resulting model of rapid standby site exploration followed by gated non-equilibrium unfolding of the 5'-UTR during accommodation provides a mechanistic understanding of how translation efficiency is governed by riboswitches and other dynamic structure motifs embedded upstream of the translation initiation site of bacterial mRNAs.
Asunto(s)
Iniciación de la Cadena Peptídica Traduccional , Riboswitch , Regiones no Traducidas 5' , Bacterias/genética , Ligandos , ARN Bacteriano/metabolismo , Ribosomas/metabolismo , Riboswitch/genéticaRESUMEN
Bacterial messenger RNA (mRNA) synthesis by RNA polymerase (RNAP) and first-round translation by the ribosome are often coupled to regulate gene expression, yet how coupling is established and maintained is ill understood. Here, we develop biochemical and single-molecule fluorescence approaches to probe the dynamics of RNAP-ribosome interactions on an mRNA with a translational preQ1-sensing riboswitch in its 5' untranslated region. Binding of preQ1 leads to the occlusion of the ribosome binding site (RBS), inhibiting translation initiation. We demonstrate that RNAP poised within the mRNA leader region promotes ribosomal 30S subunit binding, antagonizing preQ1-induced RBS occlusion, and that the RNAP-30S bridging transcription factors NusG and RfaH distinctly enhance 30S recruitment and retention, respectively. We further find that, while 30S-mRNA interaction significantly impedes RNAP in the absence of translation, an actively translating ribosome promotes productive transcription. A model emerges wherein mRNA structure and transcription factors coordinate to dynamically modulate the efficiency of transcription-translation coupling.
Asunto(s)
ARN Polimerasas Dirigidas por ADN/metabolismo , Ribosomas/metabolismo , Riboswitch/fisiología , Regiones no Traducidas 5' , Sitios de Unión , ARN Polimerasas Dirigidas por ADN/fisiología , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Factores de Elongación de Péptidos/metabolismo , Biosíntesis de Proteínas/genética , ARN Bacteriano/metabolismo , ARN Mensajero/metabolismo , Ribosomas/genética , Riboswitch/genética , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética/genéticaRESUMEN
Transcriptional riboswitches involve RNA aptamers that are typically found in the 5' untranslated regions (UTRs) of bacterial mRNAs and form alternative secondary structures upon binding to cognate ligands. Alteration of the riboswitch's secondary structure results in perturbations of an adjacent expression platform that controls transcription elongation and termination, thus turning downstream gene expression "on" or "off." Riboswitch ligands are typically small metabolites, divalent cations, anions, signaling molecules, or other RNAs, and can be part of larger signaling cascades. The interconnectedness of ligand binding, RNA folding, RNA transcription, and gene expression empowers riboswitches to integrate cellular processes and environmental conditions across multiple timescales. For a successful response to an environmental cue that may determine a bacterium's chance of survival, a coordinated coupling of timescales from microseconds to minutes must be achieved. This review focuses on recent advances in our understanding of how riboswitches affect such critical gene expression control across time.
RESUMEN
The widespread Mn2+-sensing yybP-ykoY riboswitch controls the expression of bacterial Mn2+ homeostasis genes. Here, we first determine the crystal structure of the ligand-bound yybP-ykoY riboswitch aptamer from Xanthomonas oryzae at 2.96 Å resolution, revealing two conformations with docked four-way junction (4WJ) and incompletely coordinated metal ions. In >100 µs of MD simulations, we observe that loss of divalents from the core triggers local structural perturbations in the adjacent docking interface, laying the foundation for signal transduction to the regulatory switch helix. Using single-molecule FRET, we unveil a previously unobserved extended 4WJ conformation that samples transient docked states in the presence of Mg2+. Only upon adding sub-millimolar Mn2+, however, can the 4WJ dock stably, a feature lost upon mutation of an adenosine contacting Mn2+ in the core. These observations illuminate how subtly differing ligand preferences of competing metal ions become amplified by the coupling of local with global RNA dynamics.
Asunto(s)
Magnesio/metabolismo , ARN Bacteriano/química , ARN Bacteriano/metabolismo , Riboswitch/fisiología , Transducción de Señal , Xanthomonas/metabolismo , Sitios de Unión , Cristalografía por Rayos X , Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Lactococcus lactis/genética , Lactococcus lactis/metabolismo , Ligandos , Manganeso/metabolismo , Modelos Moleculares , Conformación Molecular , Simulación de Dinámica Molecular , Mutación , Conformación de Ácido Nucleico , ARN Bacteriano/genéticaRESUMEN
Species in the cycad genus Encephalartos are listed in CITES Appendix I and as Threatened or Protected Species in terms of South Africa's National Environmental Management: Biodiversity Act (NEM:BA) of 2004. Despite regulations, illegal plant harvesting for medicinal trade has continued in South Africa and resulted in declines in cycad populations and even complete loss of sub-populations. Encephalartos is traded at traditional medicine markets in South Africa in the form of bark strips and stem sections; thus, determining the species traded presents a major challenge due to a lack of characteristic plant parts. Here, a case study is presented on the use of DNA barcoding to identify cycads sold at the Faraday and Warwick traditional medicine markets in Johannesburg and Durban, respectively. Market samples were sequenced for the core DNA barcodes (rbcLa and matK) as well as two additional regions: nrITS and trnH-psbA. The barcoding database for cycads at the University of Johannesburg was utilized to assign query samples to known species. Three approaches were followed: tree-based, similarity-based, and character-based (BRONX) methods. Market samples identified were Encephalartos ferox (Near Threatened), Encephalartos lebomboensis (Endangered), Encephalartos natalensis (Near Threatened), Encephalartos senticosus (Vulnerable), and Encephalartos villosus (Least Concern). Results from this study are crucial for making appropriate assessments and decisions on how to manage these markets.
Asunto(s)
Cycadopsida/clasificación , Cycadopsida/genética , Código de Barras del ADN Taxonómico , Medicina Tradicional , Biodiversidad , ADN Intergénico , ADN de Plantas , Filogenia , SudáfricaRESUMEN
AIM: Present study aimed to elucidate the suppression of serum lipids by gamma- and delta-tocotrienol (γδT3). METHODS: The lipid-lowering effects of γδT3 were investigated using HepG2 liver cell line, hypercholesterolemic mice and borderline-high cholesterol patients. RESULTS: In-vitro results demonstrated two modes of action. First, γδT3 suppressed the upstream regulators of lipid homeostasis genes (DGAT2, APOB100, SREBP1/2 and HMGCR) leading to the suppression of triglycerides, cholesterol and VLDL biosyntheses. Second, γδT3 enhanced LDL efflux through induction of LDL receptor (LDLr) expression. Treatment of LDLr-deficient mice with 1 mg/day (50 mg/kg/day) γδT3 for one-month showed 28%, 19% reduction in cholesterol and triglyceride levels respectively, whereas HDL level was unaltered. The lipid-lowering effects were not affected by alpha-tocopherol (αTP). In a placebo-controlled human trial using 120 mg/day γδT3, only serum triglycerides were lowered by 28% followed by concomitant reduction in the triglyceride-rich VLDL and chylomicrons. In contrast, total cholesterol, LDL and HDL remained unchanged in treated and placebo groups. The discrepancies between in-vitro, in-vivo and human studies may be attributed to the differential rates of post-absorptive γδT3 degradation and LDL metabolism. CONCLUSION: Reduction in triglycerides synthesis and transport may be the primary benefit caused by ingesting γδT3 in human.
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Cromanos/farmacología , Lipoproteínas VLDL/metabolismo , Hígado/efectos de los fármacos , Triglicéridos/biosíntesis , Vitamina E/análogos & derivados , Animales , Apolipoproteína B-100/genética , Apolipoproteína B-100/metabolismo , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular , Células Cultivadas , Diacilglicerol O-Acetiltransferasa/genética , Diacilglicerol O-Acetiltransferasa/metabolismo , Femenino , Humanos , Hidroximetilglutaril-CoA Reductasas/genética , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hígado/citología , Hígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Noqueados , ARN Mensajero/genética , Receptores de LDL/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Triglicéridos/metabolismo , Vitamina E/farmacologíaRESUMEN
The hitherto unknown 2-isopropyl-6,8-dibromo-4H-3,1-benzoxazin-4-one (2) was subjected to condensation with either primary or secondary amines affording the benzamide derivatives (3-7), while with alcohols in presence of the base, corresponding esters were obtained (8 and 9). Acylation of the hydrazide (12) or its cyclized form (13) gave (14-17). The quinazolinone derivative (18) was obtained either when (12) was reacted with nitrous acid or via fusion of (2) with ammonium acetate. The thione (20) which was obtained via reaction of (18) with Lawesson's reagent, was subjected to either alkylation yielding (21-25) or desulphurization with primary amines affording (26 and 27). Treatment of (18) as well as (20) with a chlorinating agent provided (29, 30) and (28, 29) mixtures, respectively. Ten of our compounds were examined against Sclerotium cepivorum as well as Botrytis allii on PDA media. These compounds showed a significant reduction of mycelial growth and scleratia number of these fungi which cause the white rot and neck rot diseases of onion.
Asunto(s)
Basidiomycota/efectos de los fármacos , Botrytis/efectos de los fármacos , Fungicidas Industriales/síntesis química , Oxazinas/síntesis química , Quinazolinas/síntesis química , Fungicidas Industriales/química , Fungicidas Industriales/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Cebollas/microbiología , Oxazinas/química , Oxazinas/farmacología , Quinazolinas/química , Quinazolinas/farmacología , Relación Estructura-ActividadRESUMEN
An 82-year-old male patient was admitted for liver dysfunction. Laboratory test showed the following data; aspartate aminotransferase (AST) 79 IU/l, alanine aminotransferase (ALT) 28 IU/l, total bilirubin (T. Bil) 0.9 U, zinc sulfate turbidity test (ZTT) 48.9 U, gamma-globulin 4.9 g/dl, immunoglobulin G (IgG) 5,046 mg/dl, anti-nuclear antibodies x 320, anti-mitochondrial antibodies (-), hepatitis B virus surface antigen (HBsAg) (-), HBcAb (-), anti-hepatitis C virus (anti-HCV) (-), hepatitis C virus (HCV-RNA) (-), anti-hepatitis G virus (anti-HGV) (-), alpha-fetoprotein 306.8 ng/ml, carcinoembryonic antigen (CEA) 2.3 ng/ml, carbohydrate antigen (CA) 19-9 77.2 U/ml. Abdominal ultrasonography and computed tomography showed a large mass occupying most of the right lobe and portal thrombosis in the liver. Liver biopsy revealed cirrhosis with inactive hepatitis in the nontumorous lesion and well-differentiated hepatocellular carcinoma in the tumorous lesion. We report a rare case of an aged male patient with autoimmune hepatitis complicated by hepatocellular carcinoma.
Asunto(s)
Carcinoma Hepatocelular/complicaciones , Hepatitis Autoinmune/complicaciones , Neoplasias Hepáticas/complicaciones , Anciano , Anciano de 80 o más Años , Angiografía , Carcinoma Hepatocelular/diagnóstico , Hepatitis Autoinmune/diagnóstico , Humanos , Pruebas de Función Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Tomografía Computarizada por Rayos XRESUMEN
A protein-independent fibrosarcoma, Gc-4 PF, grows exponentially in a protein-free medium. The doubling time (approximately 26 h) was similar to that of the serum-dependent parental clone, Gc-4 SD cultivated in the presence of fetal calf serum (FCS). We demonstrated here that the protein-free cultivation of Gc-4 PF cells concomitantly activates apoptotic phenotypes (one third of total cell population), including typical morphology, high uptake of Hoechst 33342 dye, and cleavage of DNA to large fragments, as observed in protein-deprived Gc-4 SD cell previously. Gc-4 SD cells arrested in the G0/G1-phase in response to the protein-free condition. In contrast, Gc-4 PF cells did not reach G0/G1 arrest in the protein-free condition; instead the durations of both G0/G1 and G2-phases were markedly reduced. The estimation of one cell cycle duration revealed that the cell division cycle was accelerated to 1.7 (27 h/15.4 h)-fold. Then the growth kinetics was able to be verified quantitatively by both the cell division rate and apoptotic cell loss. Protein-free cultivation resulted in slight down-regulation of c-myc protein in both cell types, while the down-regulation of p34cdc2, shown clearly in Gc-4 SD cells, was avoided in Gc-4 PF cells. Interestingly, while the expression of p53 was not affected in Gc-4 SD cells in response to the protein-free condition, the suppressor gene product expression was suppressed markedly in Gc-4 PF cells. These results suggest that Gc-4 PF cells may have acquired an ability to accelerate cell division by shortening the cell cycle duration to maintain a proper growth rate in response to intrinsic apoptosis activation with, at least in part, a suppression of p53 expression as well as an escape of down-regulation of p34cdc2.
Asunto(s)
Muerte Celular/fisiología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Proteína Quinasa CDC2/biosíntesis , Proteína Quinasa CDC2/efectos de los fármacos , Recuento de Células/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Muerte Celular/efectos de los fármacos , División Celular/efectos de los fármacos , División Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo/química , Medios de Cultivo/farmacología , Medio de Cultivo Libre de Suero/farmacología , Ratones , Ratones Endogámicos C3H , Mitosis/efectos de los fármacos , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/efectos de los fármacos , Proteínas/farmacología , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Proteínas Proto-Oncogénicas c-myc/efectos de los fármacos , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/fisiología , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/efectos de los fármacosRESUMEN
The hitherto unknown bis[quinazolin-4-one-2-yl]-m-phenylene (2d), and its 3-N-substituted derivatives were prepared from the corresponding bis[3,1-benzoxazin-4-one-2-yl]-m-phenylene (1) as precursor. The quinazolinone derivative 2d was converted into bis[quinazolin-4-thioxo-2-yl]-m-phenylene (3) via different routes, bis[4-chloroquinazolin-2-yl]-m-phenylene (8) and bis[4-hydrazinoquinazolin-2-yl]-m-phenylene (11), respectively. The structures of the compounds 2, 3, 8, and 11 were supported by elemental, spectroscopic analysis as well as, chemical proofs. Biological activities of some of the produced compounds were evaluated.
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Antiinfecciosos/síntesis química , Quinazolinas/síntesis química , Antibacterianos , Antiinfecciosos/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Quinazolinas/farmacología , Espectrofotometría InfrarrojaRESUMEN
A 68-year-old man developed severe consciousness disturbance after daily administration of 20 mg omeprazole for four days for the treatment of bleeding gastric ulcer. Systemic investigation revealed severe hyponatremia (111 meq/liter). Consciousness did not become clear until his sodium intake was increased to 480 meq/day, and his serum sodium concentrations reached 130 meq/liter. After the discontinuation of omeprazole, his serum sodium levels returned to the normal range with only minimum supplementation of sodium in the form of dietary sodium chloride intake of 10 g/day. Although the mechanism of hyponatremia induced by omeprazole is not clear, an excessive loss of urinary sodium appears to be more likely than water retention with an increase in fluid intake. The literature was also reviewed.
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Antiulcerosos/efectos adversos , Trastornos de la Conciencia/inducido químicamente , Hiponatremia/inducido químicamente , Omeprazol/efectos adversos , Anciano , Humanos , MasculinoRESUMEN
The effect of ethanol concentration on cloned gene expression in recombinant Saccharomyces cerevisiae strain 20B-12 containing one of two plasmids, pNA3 and pNA7, was investigated in batch cultures. Plasmids pNA3 and pNA7 contain the alpha-amylase gene under the control of the SUC2 or PGK promoter, respectively. When the ethanol concentration was controlled at 2 to 5 g/L, the gene expressions were two times higher than those at 20 g/L ethanol. The increase the gene expression by maintaining both the ethanol and glucose concentrations at low levels, a fuzzy controller was developed. The concentrations of glucose and ethanol were controlled simultaneously at 0.15 and 2 g/L, respectively, in the production phase using the fuzzy controller in fed-batch culture. The synthesis of alpha-amylase was induced by the low glucose concentration and maintained at a high level of activity by regulating the ethanol concentration at 2 g/L. The secretory alpha-amylase was induced by the low glucose concentration and maintained at a high level of activity by regulating the ethanol concentration at 2 g/L. The secretory alpha-amylase activities of cells harboring plasmids pNA3 and pNA7 in fed-batch culture were 175 and 395 U/mL, and their maximal specific activities 7.7 and 12.4 U/mg dry cells, respectively. These values are two to three times higher in activity and three to four times higher in specific activity than those obtained when glucose only was controlled.
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To examine how varieties of the subjective experience of schizophrenia (SES) can be categorized, a self-report questionnaire consisting of 150 items from the SES in Japanese was administered to 237 Japanese schizophrenic inpatients, and the results were analyzed through a multivariate method. The first factor represents loss of focus and adequacy of thoughts, behavior, and interpersonal perception; it resembles negative symptoms and coincides with the basic symptoms of schizophrenia reported by anthropological psychiatrists. The second factor represents automatic and excessive thoughts and affective loading, and overlaps "the tremble" of Conrad and the mental automatism of de Clerambault. Both signify different combinations of experiences from conventional descriptive symptoms, and may represent more suitable ways to describe the SES.
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Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Rol del Enfermo , Adulto , Depresión/diagnóstico , Depresión/psicología , Femenino , Hospitalización , Humanos , Relaciones Interpersonales , Japón , Masculino , Persona de Mediana Edad , Inventario de Personalidad/estadística & datos numéricos , Psicometría , Lenguaje del Esquizofrénico , Autoimagen , Conducta Social , Percepción Social , PensamientoRESUMEN
Two adult patients with acute mixed lineage leukemia (AMLL) having combined Philadelphia chromosome (Ph1) positivity and monosomy 7 are presented. The phenotypes of leukemic blasts from both cases were almost same (early B-lymphoid lineage and myeloid lineage); CD10+, CD13+, CD19+. HLA-DR+, and dual-color analysis showed simultaneous expression of CD10 (CD19) and CD13 antigens in individual blasts (biphenotypic) in both cases. On molecular analysis, the leukemic blasts showed rearrangement in the first intron of the BCR gene with breakpoint just outside of 3' end of m-BCR-2 (bcr 3) in case 1, and in the M-BCR in case 2. Immunoglobulin heavy chain gene (IgH) rearrangement was noted in both cases, but rearrangement of the T-cell receptor beta-chain gene (TCR beta) was detected only in case 1. Clinically, both cases achieved complete remission by the combination chemotherapy consisting of L-asparaginase, doxorubicin, vincristine, and prednisolone (L-AdVP). In remission, all these molecular abnormalities disappeared in both patients. These results suggest that the Ph1-positive and monosomy 7 AMLL in adults is de novo acute leukemia with both early B-lymphoid and myeloid phenotypes and may arise from malignant transformation of pluripotent stem cell, and expresses a heterogenous rearrangement pattern of the BCR gene.
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Linfoma de Burkitt/genética , Cromosomas Humanos Par 7 , Células Madre Hematopoyéticas/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Monosomía , Cromosoma Filadelfia , Enfermedad Aguda , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Linfoma de Burkitt/inmunología , Linfoma de Burkitt/patología , Antígenos CD13 , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Fragilidad Cromosómica , Reordenamiento Génico , Reordenamiento Génico de Cadena Pesada de Linfocito B , Humanos , Inmunofenotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Familia de Multigenes , Neprilisina/análisis , FenotipoRESUMEN
Cloned gene expression in recombinant Saccharomyces cerevisiae 20B-12 containing three different plasmids was compared in batch and fed-batch cultures. The plasmids pNA3, pNA7, and pNA9 contain the alpha-amylase gene under the control of SUC2, PGK, and GAL7 Promoters, respectively. The synthesis of alpha-amylase was therefore induced by low glucose concentration for the SUC2 and PGK promoters, and by galactose for GAL7 promoter. The specific cell growth rates were similar among cells harboring the three different plasmids; they decreased from 0.35 to 0.38 h(-1) during the cell growth phase to 0.03 to 0.06 h(-1) during the production phase. The secretory alpha-amylase activity of cells harboring plasmid pNA7 was 129 U/mL in fed-batch culture, which was 1.4 and 2 times as high as the activities of cells harboring plasmids pNA3 and pNA9, respectively. The secretion ratios (amount of extracellular alpha-amylase activity/amounts of total alpha-amylase activity) of cells harboring plasmids pNA3, pNA7, and pNA9 were 91.4%, 94.5%, and 95.3%, respectively.
RESUMEN
The design of new heterocyclic derivatives as modulatory agents at EAA receptors is described. In particular, the potent and selective activity at the NMDA receptor of trans-4-hydroxypipecolic acid-4-sulfate, as well as the neuroprotective properties of substituted thiokynurenates, a new class of competitive antagonists at the glycine site of the NMDA receptor complex, are reported.