RESUMEN
A catalytic system has been developed for the direct alkylation of α-C-H bonds of aniline derivatives with strained C-C σ-bonds. This method operates through a photoredox mechanism in which oxidative formation of aminoalkyl radical intermediates enables addition to a bicyclobutane derivative, giving rise to α-cyclobutyl N-alkylaniline products. This mild system proceeds through a redox- and proton-neutral mechanism and is operational for a range of substituted arylamine derivatives.
RESUMEN
The direct addition of pyridine and diazine units to electron-poor alkenes has been achieved via a redox radical mechanism that is enabled by limiting the effective concentration of the hydrogen-atom source. The described method is tolerant of acidic functional groups and is generally applicable to the union of a wide range of Michael acceptors and 6-membered heterocyclic halides.
RESUMEN
A robust system for the preparation of ß-heteroaryl α-amino acid derivatives has been developed using photoredox catalysis. This system operates via regiospecific activation of halogenated pyridines (or other heterocycles) and conjugate addition to dehydroalanine derivatives to deliver a wide range of unnatural amino acids. This process was conducted with good efficiency on large scale, the application of these conditions to amino ketone synthesis is shown, and a simple protocol is given for the preparation of enantioenriched amino acid synthesis, from a number of radical precursors.
RESUMEN
In two investigations, 50% of non-violent convicted felons, who avoided incarceration by participating in a day reporting programme, reported a prior history of head injury and current problems in cognitive and emotional functioning. Only 5% of a college sample in the first investigation and 15% of a community sample in the second investigation reported prior head injury. In a third investigation, 83% of felons who had reported a history of head injury also reported a date for their head injury that preceded the date of their first encounter with law enforcement. Some participants reported no trouble with the law until after experiencing a head injury that occurred in their late thirties. Considering the research reported here and elsewhere in the literature, it appears that many serious crimes follow a head injury. One implication of the findings reported here is that many crimes might not occur if people with head injury were given prompt and comprehensive treatment after the injury.
Asunto(s)
Síntomas Afectivos/diagnóstico , Daño Encefálico Crónico/diagnóstico , Lesiones Encefálicas/diagnóstico , Trastornos del Conocimiento/diagnóstico , Crimen/psicología , Adaptación Psicológica , Adulto , Síntomas Afectivos/epidemiología , Síntomas Afectivos/psicología , Daño Encefálico Crónico/epidemiología , Daño Encefálico Crónico/psicología , Lesiones Encefálicas/epidemiología , Lesiones Encefálicas/psicología , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/psicología , Crimen/estadística & datos numéricos , Estudios Transversales , Centros de Día , Femenino , Humanos , Incidencia , Indiana/epidemiología , Masculino , Persona de Mediana Edad , Prisioneros/psicología , Prisioneros/estadística & datos numéricos , Valores de Referencia , Rehabilitación Vocacional , Factores de RiesgoAsunto(s)
Conducto Colédoco , Divertículo del Colon/complicaciones , Migración de Cuerpo Extraño/etiología , Conducto Hepático Común , Stents , Anciano , Colangiopancreatografia Retrógrada Endoscópica , Colon/diagnóstico por imagen , Colonoscopía , Divertículo del Colon/diagnóstico , Divertículo del Colon/terapia , Migración de Cuerpo Extraño/diagnóstico , Migración de Cuerpo Extraño/terapia , Humanos , Tomografía Computarizada por Rayos XRESUMEN
The collagens of normal and end-stage alcoholic cirrhotic human liver were investigated. Mild conditions of pepsin digestion were employed to preserved the more pepsin sensitive type IV collagen molecules while increasingly more harsh conditions were used which solubilized the type I and type III hepatic collagens. The total hepatic collagen content was elevated from 1.8-2.1 in normal liver to 7.3-8.2 percent in the end-stage alcoholic liver. The graded pepsin digestion resulted in solubilization of 76-90 percent of the total hepatic collagen. The genetically distinct types of collagen were fractionated into types I, III, IV and V preparations using judicious salt precipitation from dilute acid and neutral pH solutions. The average distribution of collagen was 42.5, 39.5, 6.9 and 10.6 percent types I, III, IV and V collagen respectively in normal liver compared to 56.6, 28.0, 5.5 and 9.6 percent respectively in the end-stage alcoholic livers. An additional 0.6 and 0.5 percent in normal and end-stage cirrhotic liver respectively were located in a fraction separating out of the salt concentration required for type VI collagen. The type IV collagen of basement membrane was separated into the constituent 95Kda alpha 1(IV) and alpha 2(IV) polypeptide chains by Agarose A 5m gel filtration with subsequent (carboxymethyl) CM-cellulose chromatography. These chains were indistinguishable from similar chains of type IV collagen isolated previously from human placenta. The type V collagen alpha chains, alpha 1(V) and alpha 2(V) were purified by a combination of Diethylaminoethyl (DEAE) and CM-cellulose chromatography. The individual chains were fragmented with cyanogen bromide to yield 9 peptides from the alpha 1(V) chain and 10 peptides from the alpha 2(V) collagen chain. These were purified and analyzed for amino acid content and molecular weight. The study suggests that all collagen types were elevated in the end-stage alcoholic liver, but type I collagen was disproportionately increased over all other collagens. These results are consistent with previous studies which demonstrated an elevated type I collagen in other fibrotic conditions such as lung fibrosis and hypertrophic scar. They do not, however, agree with the suggested disproportionate elevation of type V collagen in human alcoholic liver. The reasons for this discrepancy are discussed.
Asunto(s)
Colágeno/aislamiento & purificación , Cirrosis Hepática Alcohólica/metabolismo , Hígado/análisis , Aminoácidos/metabolismo , Cromatografía en Gel , Bromuro de Cianógeno , Electroforesis en Gel de Poliacrilamida , Glicósidos/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Pepsina A , SolubilidadRESUMEN
A hepatic fibrogenic factor (HFF) isolated from fibrotic rat livers has previously been shown to stimulate the transcription of type I procollagen genes in cultured fibroblasts (Raghow, R., Gossage, D., Seyer, J. M., and Kang, A.H. (1984) J. Biol. Chem. 259, 12718-12723). To test if the expression of other collagen genes was similarly affected by the fibrogenic factor, we measured the rates of types I, III, and V procollagen synthesis in two different cell lines after treatment with HFF. The effect of fibrogenic factor on types I and III procollagens was tested in rat fibroblasts, while a human rhabdomyosarcoma cell line was used to evaluate the effect of HFF on type V procollagen synthesis. Incubation with rat fibroblasts resulted in a 3-4-fold stimulation of the synthesis of both types I and III procollagens in a time-dependent manner. The stimulated rates of types I and III procollagen synthesis accompanied an increase in the steady-state levels of their corresponding mRNAs. When A204 cells, which are derived from a rhabdomyosarcoma and exclusively synthesize type V procollagen, were incubated with the fibrogenic factor, a 3-4-fold stimulation of the synthesis of both pro-alpha 1(V) and pro-alpha 2(V) chains was seen. Using a cDNA probe for pro-alpha 2(V), we also observed that there was a 2-3-fold increase in the steady-state level of pro-alpha 2(V) mRNA in A204 cells after treatment with the fibrogenic factor. In both rat fibroblasts and A204 cells the steady-state levels of beta-actin mRNA were minimally affected by fibrogenic factor, suggesting that the procollagen genes were preferentially affected. Since types I, III, and V collagens are present in the normal liver and accumulate aberrantly in the fibrotic liver, we suggest that fibrogenic factor may play an important role in determining the altered collagen composition of the fibrotic liver. Based on these data, we also speculate that the regulation of the biosynthesis of a variety of procollagens in diverse cell types by HFF possibly occurs by a common mechanism.
Asunto(s)
Cirrosis Hepática Experimental/metabolismo , Hígado/análisis , Fosfolípidos/farmacología , Procolágeno/genética , Proteínas/farmacología , Transcripción Genética/efectos de los fármacos , Animales , ADN/análisis , Femenino , Humanos , Procolágeno/biosíntesis , ARN Mensajero/metabolismo , Ratas , Ratas EndogámicasRESUMEN
We evaluated the effects of a synthetic copy of a highly conserved portion (residues 225-246) of the COOH-propeptide of human pro-alpha 2(I) procollagen on collagen, fibronectin, and total protein synthesis by human fibroblasts. Incubation of COOH-propeptide 225-246 with fibroblasts resulted in a concentration-dependent inhibition of both type I procollagen and fibronectin when compared with controls; a 50% inhibition of both fibronectin and type I collagen was observed at a concentration of 45 microM. Since the overall cellular protein synthesis was only minimally affected, COOH-propeptide appeared to specifically inhibit collagen and fibronectin synthesis. The peptide was nontoxic to cells and the inhibition was completely reversible upon removal of the peptide. We measured the steady-state levels of mRNAs coding for procollagen, fibronectin, and beta-actin by hybridization to specific recombinant cDNA probes; there was no significant change in the steady-state level of mRNAs of the three proteins. These results strongly suggest that the biosynthesis of procollagen and fibronectin in COOH-propeptide-treated cells is inhibited at a post-transcriptional level. These data establish a link between collagen and fibronectin synthesis and further define the important interaction of these molecules in the formation of the extracellular matrix.
Asunto(s)
Colágeno/biosíntesis , Fibronectinas/biosíntesis , Fragmentos de Péptidos/síntesis química , Procolágeno/síntesis química , Secuencia de Aminoácidos , Células Cultivadas , Cromatografía Líquida de Alta Presión , Fibroblastos/metabolismo , Humanos , Pulmón/citología , Pulmón/metabolismo , Fragmentos de Péptidos/farmacología , Procolágeno/farmacología , Transcripción GenéticaRESUMEN
Three cultivars of Ilex crenata: 'Helleri', 'Convexa', and 'Rotundifolia' were inoculated with either Criconemoides xenoplax, Helicotylenchus dihystera, Hoplolaimus galeatus, Trichodorus cltristiei, or Tylenchorhynchus claytoni at 0, 200 (low), or 2,000 (high) nematodes/ 15-cm diam pot. Plants were kept in the greenhouse 10 mo prior to transplanting into 2.25 m(2) field plots. Helleri was severely stunted by C. xenoplax. Criconemoides xenoplax and T. claytoni caused lower plant vigor and top weights of Rotundifolia after 3 years. Above-ground symptoms included stunting, chlorosis, and leaf drop. Convexa was not susceptible to the nematodes tested. Low and high initial populations of the five nematodes tended to reach equilibria over the 3-year sampling period. Helicotylenchus dihystera and C. xenoplax occurred in the greatest densities regardless of host. None of the test plants were damaged by H. dihystera. Convexa was the least suitable host for nematode reproduction. Hoplolaimus galeatus, which was originally isolated from cotton, failed to reproduce or survive on any plant tested. Nematode densities over the 3-year sampling period did not always lit a linear regression model.
RESUMEN
American boxwood, Buxus sempervirens var. globosum, was tolerant of Helicotylenchus dihystera [in field microplots] as measures of plant growth were similar to the control and nematode densities were maintained at high levels (1,705-1,810/500 cm(3) soil after 29 months). Boxwood was intolerant of Pratylenchus vulnus at initial densities of 163, 281, or 475 nematodes per 500 cm(3) soil. In comparisons with those of controls, vigor ratings of boxwood after 14 months were much lower at all densities of this nematode. Nematode density was not directly related to vigor rating. However, initial nematode density was directly proportional to growth suppression of boxwood as measured by the difference of the product of final plant height x width or by the difference of the plant surface area determined from a standardized photograph as compared to those of controls. A nematode density of 160/500 cm(3) of soil was found to suppress growth by 50%. Populations of P. vulnus declined, according to a linear function, with time after reaching over 7,100 nematodes/500 cm(3) of soil taken from the root zones of boxwoods. Ninety-five percent of the P. vulnus population died between 15 and 20 months after soil infestation.