RESUMEN

We have measured Raman spectra of collective O-H stretching vibration of water clusters in polyrotaxane and pseudopolyrotaxane aqueous solutions and the aqueous solutions of their constituent molecules. The intensities of the collective bands of water clusters in the polyrotaxane and pseudopolyrotaxane solutions were approximately equal to that of their solvents. On the other hand, those in the solutions of linear polymeric chains and cyclic molecules were smaller. These results indicate that the water molecules in the solvents cannot approach to interact with the hydrophobic parts of the constituent molecules sterically when the constituent molecules form the inclusion complexes. Thus, the polyrotaxane and pseudopolyrotaxane molecules are observed as inert in terms of molecular interaction with water, although the constituent molecules have hydrophobic parts in their structure.

Asunto(s)

Ciclodextrinas/análisis , Ciclodextrinas/química , Poloxámero/análisis , Poloxámero/química , Rotaxanos , Espectrometría Raman/métodos , Agua/química , Hidrógeno/química , Modelos Químicos , Oxígeno/química

RESUMEN

PURPOSE: To clarify the cellular origin of extranodal marginal-zone B-cell lymphoma (EZML) of the mucosa-associated lymphoid tissue (MALT) type in ocular adnexa, the somatic mutation was analyzed in the immunoglobulin heavy-chain variable region (VH) gene. METHODS: Eight cases of EZML in the orbit and four in the conjunctiva were studied. The VH genes were amplified by a seminested PCR and sequenced directly. These were compared with the closest published VH germline segments to determine the somatic mutation frequency. Intraclonal microheterogeneity, which was termed the ongoing mutation frequency in the current study, was estimated by counting the number of single nucleotide substitutions in individual clones and dividing by the total number of nucleotides analyzed. Nine cases of gastrointestinal EMZL were also examined for comparison. RESULTS: The somatic mutation frequency varied between 2.0% and 12.7%, with a mean value of 7.9%. Ten cases with intraclonal microheterogeneity showed between one and six further substitutions. The average of ongoing mutation frequency was 0.11%, with a range of 0% to 0.25%. In the gastrointestinal EMZLs, the average of somatic mutation frequency was 8.5% (1.5%-14.2%) and of ongoing mutation frequency was 0.51% (0.25%-0.75%). CONCLUSIONS: The average of ongoing mutation frequency in ocular adnexal EMZL was lower than that in gastrointestinal EMZL. Both ocular adnexal and gastrointestinal EMZLs are derived from postgerminal center memory B cells, but the low ongoing mutation frequencies of ocular adnexal EMZL may result from less antigen stimulation and follicular colonization in the orbit relative to gastrointestinal EMZL.

Asunto(s)

Neoplasias de la Conjuntiva/genética , Genes de Inmunoglobulinas , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma de Células B/genética , Neoplasias Orbitales/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Análisis Mutacional de ADN , ADN de Neoplasias/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Neoplasias Gástricas/genética

RESUMEN

We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was estimated from the number of further single base-substitutions, expressed as a percentage of the total number of nucleotides in 10 cloned PCR products for each case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases) and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024). These data may indicate that the cell origin of CD5+ DLBCL is different from that of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived from this unique subset.

Asunto(s)

Antígenos CD5/genética , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Linfoma de Células B/inmunología , Linfoma de Células B Grandes Difuso/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Cartilla de ADN , ADN de Neoplasias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Homología de Secuencia de Ácido Nucleico

RESUMEN

We have investigated 114 cases with diffuse large B-cell lymphoma (DLBCL) to clarify the characteristics of DLBCL with Epstein-Barr virus (EBV) infection. Thirteen cases (11.4%) showed EBV-encoded RNA 1 (EBER1) signals by RNA in situ hybridization. EBV-encoded latent membrane protein 1 (LMP1) and EBV-encoded nuclear antigen 2 (EBNA2) were expressed in 11 and 4 cases, respectively. Expression of CD30, Bcl-6 and immunoglobulin (Ig) was found in 92%, 31% and 23% with EBV(+) DLBCL, and in 15%, 79% and 82% with EBV(-) DLBCL, respectively. The sequence of rearranged Ig heavy chain (IgH) variable (V) region gene was analyzed in 5 cases with EBV(+) DLBCL and 61 cases with EBV(-) DLBCL. Somatic mutation was found in all cases except one with EBV(-) DLBCL. Average mutation frequency was 9.6% in EBV(+) DLBCL vs. 11.5% in EBV(-) DLBCL. The rates of replacement mutation vs. silent mutation (R / S values) in complementarity determining region II and framework region III were 2.7 and 1.5 in EBV(+) DLBCL, 2.6 and 1.4 in EBV(-) DLBCL. Crippling mutation generating a stop codon was found in 2 of 5 cases (40%) with EBV(+) DLBCL, but none of 61 cases (0%) with EBV(-) DLBCL. These findings suggest that EBV(+) DLBCL and EBV(-) DLBCL were both derived from germinal center (GC) or post-GC B cells, and EBV(+) DLBCL frequently have a non-functional IgH gene owing to crippling mutation.

Asunto(s)

Genes de Inmunoglobulinas , Herpesvirus Humano 4/aislamiento & purificación , Linfoma de Células B/virología , Linfoma de Células B Grandes Difuso/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Pueblo Asiatico , Secuencia de Bases , Niño , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Inmunofenotipificación , Japón , Linfoma de Células B/genética , Linfoma de Células B/mortalidad , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Pronóstico , Tasa de Supervivencia

RESUMEN

The immunoglobulin heavy chain gene (IgH gene) was analysed in four cases of B-cell Richter syndrome, in order to determine whether a secondary diffuse large B-cell lymphoma (DLBCL) could arise from the same clone as the initial B-cell chronic lymphocytic leukemia (B-CLL) and lymphoplasmacytoid lymphoma (LPL) or be a de novo event, and whether secondary DLBCL shows an intraclonal microheterogeneity. Both the initial B-CLL and secondary DLBCL in two cases expressed CD5 antigen. Both samples of the initial B-CLL or LPL and the secondary DLBCL in three cases were examined for comparison. The polymerase chain reaction-amplified IgH gene of secondary DLBCL in two cases (CD5+ case and CD5- case) were different from those of the initial B-CLL, revealing a new malignant clone. The other case (CD5-) showed that secondary DLBCL had a sequence identical to the initial LPL, indicating the same clonal origin. The variable region of the IgH gene of secondary DLBCL (CD5+ two cases and CD5- two cases) exhibited a 0.5-9.0% somatic mutation range and no intraclonal microheterogeneity.

Asunto(s)

Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/genética , Linfoma de Células B/genética , Linfoma de Células B Grandes Difuso/genética , Neoplasias Primarias Secundarias/genética , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Antígenos CD5/análisis , Células Clonales , Cartilla de ADN/química , Humanos , Cadenas Pesadas de Inmunoglobulina/análisis , Inmunohistoquímica , Leucemia Linfocítica Crónica de Células B/química , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B/química , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/química , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas de Neoplasias/análisis , Neoplasias Primarias Secundarias/química , Neoplasias Primarias Secundarias/patología , Reacción en Cadena de la Polimerasa

RESUMEN

We have analyzed the immunoglobulin heavy chain (VH) gene variable regions (CDR2 and FW3) of 101 Japanese cases with peripheral B cell neoplasms. When all except one case with a deletion were graphed by frequency of replacement mutation, the 100 cases could be separated into two groups: 24 cases with zero, one and two mutations (germline or low frequency of somatic mutation); and 76 cases with three or more mutations (medium to high frequency of somatic mutation). While most mantle cell lymphoma cases (11/13) showed germline or low frequency of somatic mutation, all cases of mucosa-associated lymphoid tissue (MALT) lymphoma (11/11), follicular lymphoma (three of three cases), plasma cell myeloma (seven of seven cases) and most cases of diffuse large B cell lymphoma (DLBCL; 42/47) belonged to the latter group. These 76 cases, therefore, may be considered to show somatic hypermutation. More than half of chronic lymphocytic leukemia/small lymphocytic lymphoma cases (CLL/SLL; eight of 13) showed a hypermutated VH gene and the ratio of replacement mutation: silent mutation in CDR2 of CLL/SLL was considerably higher compared with DLBCL and MALT lymphoma, showing somatic hypermutation. When comparing VH gene type of B cell-CLL (B-CLL) among our series and those in the literature, more cases of CD5+ B-CLL in the Western literature have the VH5 and VH6 family types, while more cases in Japan are reported to have VH4 family. The occurrence of VH families in B-CLL between Japanese and Western people seems to be comparable.

Asunto(s)

Reordenamiento Génico de Cadena Pesada de Linfocito B/genética , Genes de Inmunoglobulinas/genética , Región Variable de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/genética , Linfoma de Células B/genética , Anciano , Análisis Mutacional de ADN , ADN de Neoplasias/análisis , Femenino , Frecuencia de los Genes , Humanos , Japón , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B/metabolismo , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Mutación Puntual , Reacción en Cadena de la Polimerasa

RESUMEN

To clarify the cell origin of CD5+ diffuse large B-cell lymphoma (DLBCL), we analyzed and compared the variable region of the immunoglobulin heavy chain gene (VH gene) in eight cases of CD5+ DLBCL and 23 cases of other CD5+ B-cell neoplasms; 10 cases of chronic lymphocytic leukemia (CLL), one case of small lymphocytic lymphoma, one case of hairy cell leukemia, and 11 cases of mantle cell lymphoma. CD5+ DLBCL were comprised of two cases of de novo lymphoma of nodal origin, five cases of de novo lymphoma of extranodal origin, and one case of Richter transformation. Whereas all cases of mantle cell lymphoma except one showed a germ line or low mutation frequency of the rearranged VH gene, the rearranged VH genes in both CD5+ CLL and CD5+ DLBCL were heterogeneous. The degree of somatic mutation of CD5+ CLL and CD5+ DLBCL ranged between approximately 0 to 15.0% and 0.7 to 12.9%, respectively. High frequency of expression of the VH4 family in both CD5+ CLL and CD5+ DLBCL was found. Moreover, none of the three cases of CD5+ DLBCL examined exhibited intraclonal diversity. These findings may be common characteristics of the rearranged VH gene of CD5+ CLL and CD5+ DLBCL and suggested that the cell origin of CD5+ DLBCL was the same as that of CD5+ CLL.

Asunto(s)

Antígenos CD5/análisis , Genes de Inmunoglobulinas , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Linfoma de Células B/inmunología , Linfoma de Células B Grandes Difuso/inmunología , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación

RESUMEN

Multiple lymphomatous polyposis (MLP) is characterized by multiple polyps involving long segments of the gastrointestinal (GI) tract. MLP is thought to represent mantle cell lymphoma (MCL) of the GI tract; however, some cases of follicular lymphoma (FL) of the GI tract are found with a multiple polypoid appearance. In the present study, to clarify the cellular origin of MLP, clonal immunoglobulin heavy chain (IgH) gene rearrangement of four cases with MLP was amplified by polymerase chain reaction (PCR) and analyzed for the presence of somatic mutation. The IgH variable (VH) region sequences of three cases (CD5+ CD10- cyclin D1+) showed a little somatic mutation compared with the closest published germline. The other case (CD10+ CD5- cyclin D1-) was highly mutated and showed intraclonal heterogeneity (ongoing somatic hypermutation). These data indicate that three of the cases with MLP are derived from pregerminal center B cells (mantle zone B cells) and one case with MLP from germinal center B cells. Our study suggests that MLP is a heterogenous group that includes MCL and FL.

Asunto(s)

Neoplasias Gastrointestinales/inmunología , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Pólipos Intestinales/inmunología , Linfoma Folicular/inmunología , Linfoma no Hodgkin/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/metabolismo , Ciclina D1/genética , Resultado Fatal , Femenino , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/patología , Humanos , Inmunohistoquímica , Pólipos Intestinales/metabolismo , Pólipos Intestinales/patología , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

RESUMEN

Synthesis of oligonucleotide 26-mers including single 5-formyl-2'-deoxyuridine (1) or 5-formyl-2'-O-methyluridine (2) in place of thymidine at the kappaB site has been accomplished. One of the 26-mers with 1 was critically discriminated by the NFkappaB p50 homodimer in binding.

Asunto(s)

FN-kappa B/química , FN-kappa B/metabolismo , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/síntesis química , Secuencia de Bases , Sitios de Unión , ADN/química , Dimerización , Oxidación-Reducción

RESUMEN

Single 6-formylcytidine was introduced into a oligonucleotide duplex (23 mers) as a substitute for thymidine in the Myb binding sequence of 3'-TTGAC-5'. The modified duplex showed Tm of 67 degrees C, which was six degrees lower than the Tm of the native duplex. Binding affinity of the 23-mers to the Myb protein was estimated by electrophoretic mobility shift assays, and the binding was almost completely abolished.

Asunto(s)

Citidina/análogos & derivados , Oligodesoxirribonucleótidos/metabolismo , Proteínas Proto-Oncogénicas c-myb/metabolismo , Sitios de Unión , Citidina/química , Humanos , Lisina/química , Estructura Molecular , Oligodesoxirribonucleótidos/química , Unión Proteica , Proteínas Proto-Oncogénicas c-myb/química , Relación Estructura-Actividad , Especificidad por Sustrato , Temperatura

RESUMEN

Relationship and histogenesis of Hodgkin's disease (HD) and anaplastic large cell lymphoma (ALCL) still remain unclear. Recently, Reed-Sternberg cells or Hodgkin cells in HD with B cell phenotype (B-HD) are considered to originate from germinal center B cells, ALCLs of B cell phenotype (B-ALCL) are involved in diffuse large B cell lymphoma (DLBCL) as anaplastic variant, but an origin of tumor cells of B-ALCL has not been elucidated. We have therefore investigated somatic mutation of the lg heavy chain (IgH) genes among 17 cases of B-ALCL to clarify whether there is a difference in characteristic and origin of tumor cells between B-ALCL, B-HD and DLBCL. Amplificates of IgH variable (V) region of 10 cases by the polymerase chain reaction method were sequenced and compared with reported germ line configurations. Nine cases (90%) with heavily somatic mutations were found. A case with an out-of-frame rearrangement and a case with 9 base pairs insertion were included. The mutation pattern revealed the tumor cells were selected for antibody expression and discriminated from B-HD. These findings suggest the tumor cells of B-ALCL are derived from germinal center or postgerminal center (memory and effector) B cells and an origin of B-ALCL is not different from DLBCL.

Asunto(s)

Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Linfoma de Células B/genética , Linfoma Anaplásico de Células Grandes/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , ADN de Neoplasias/genética , Femenino , Reordenamiento Génico de Linfocito B , Genes de Inmunoglobulinas , Humanos , Memoria Inmunológica , Antígeno Ki-1/inmunología , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Linfoma Anaplásico de Células Grandes/inmunología , Linfoma Anaplásico de Células Grandes/patología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa

RESUMEN

5-Formyl-2'-O-methyluridine was incorporated into the various positions of oligonucleotide 26-mers containing the NF-kappa B binding sequence. Some of them showed binding selectivity toward the homo- and heterodimers of subunits of NF-kappa B.

Asunto(s)

FN-kappa B/metabolismo , Oligonucleótidos/metabolismo , Uridina/análogos & derivados , ADN/metabolismo , Dimerización , Uridina/metabolismo

Asunto(s)

Transformación Celular Neoplásica/genética , Genes p53/genética , Leucemia Prolinfocítica de Células T/genética , Linfoma/genética , Mutación , Resultado Fatal , Humanos , Linfoma/tratamiento farmacológico , Linfoma/inmunología , Masculino , Persona de Mediana Edad

RESUMEN

Mantle cell lymphoma (MCL) has a characteristic chromosomal translocation, t(11:14) (q13;q32) involving rearrangement of bcl-1 locus, and the key oncogene of bcl-1 locus in PRAD1/cyclin D1 gene that encodes the protein regarding cell cycle. Recently, several studies using immunohistochemical and molecular methods have demonstrated the overexpression of cyclin D1 mRNA/protein in cases of MCL. We have studied immunohistochemical expression of cyclin D1 protein on frozen sections of 27 cases of MCLs and evaluated the relationship between the expression of cyclin D1 and prognosis. Sixteen (59.3%) cases showed intranuclear staining of cyclin D1 protein and 6 of 7 cases examined using RT-PCR methods showed the overexpression of PRAD1/cyclin D1 mRNA. The data indicate that intranuclear staining of cyclin D1 protein is associated with the overexpression of PRAD1/cyclin D1 mRNA. The survival time of cyclin-D1 positive group was shorter than that of cyclin D1-negative group, and there was a significant difference in survival time between the two groups (p < 0.05; log-rank test). These data suggest that the MCLs with overexpression of PRAD1/cyclin D1 protein has poor prognosis, and intranuclear expression of cyclin D1 protein is a useful prognostic marker for MCL.

Asunto(s)

Ciclina D1/análisis , Linfoma no Hodgkin/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Ciclina D1/genética , Femenino , Humanos , Linfoma no Hodgkin/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/análisis

RESUMEN

The clinicopathological features, the immunophenotype, and the presence of Epstein-Barr virus (EBV)-associated genomes and gene products were examined in 17 cases of CD30+ anaplastic large cell lymphoma (ALCL) of B-cell type. Microscopically, the 17 cases were divided into ten cases of the monomorphic type and seven cases of the pleomorphic type. EBV was detected in 6 of 17 cases (38 per cent) by RNA in situ hybridization (ISH) with EBV-encoded RNA (EBER1). EBER1+ cases consisted of two cases (20 per cent) of the monomorphic type and four cases (57 per cent) of the pleomorphic type. The five EBER1+ cases showed clonality of the EBV genome by Southern blotting, consistent with the presence of EBV in a monoclonal proliferation. The EBV-encoded latent membrane protein 1 (LMP1) was found in all six EBER1+ cases and EBV-encoded nuclear antigen 2 (EBNA2) was present in two cases by immunohistochemistry. No expression of LMP1 or EBNA2 was observed in the EBER1-cases. The EBER1+ cases had a tendency for a more favourable prognosis than the EBER1-cases. It is concluded that EBV has an association with CD30+ ALCL of B-cell type in the Japanese population studied, and especially with the large pleomorphic type. EBV infection may play a pathoaetiological role and may influence clinical behaviour.

Asunto(s)

Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4/aislamiento & purificación , Linfoma Anaplásico de Células Grandes/virología , Infecciones Tumorales por Virus/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Southern Blotting , Femenino , Humanos , Técnicas para Inmunoenzimas , Inmunofenotipificación , Hibridación in Situ , Linfoma Anaplásico de Células Grandes/inmunología , Linfoma Anaplásico de Células Grandes/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Tasa de Supervivencia

RESUMEN

The relationship between the mutation of the p53 gene and the expression of the p53 protein and the Ki-67 antigen has been investigated in 115 cases with non-Hodgkin's lymphoma, using the immunohistochemical double staining technique, single-strand conformational polymorphism and DNA sequencing methods. Eighteen cases showed more than 10% of p53+ cells and the others showed a few p53+ cells presented sporadically. Alterations in the p53 gene were detected in six cases with B cell type, consisting of five cases with point mutation and one case with point mutation and 15 base pairs deletion. These six cases showed a high percentage of p53+ cells and five cases revealed that the percentage of p53+ cells was higher than that of Ki-67+ cells (p53+ cells > Ki-67+ cells). Excluding the six cases with mutation of the p53 gene, all cases revealed that the percentage of p53+ cells was less than that of Ki-67+ cells (p53+ cells < Ki-67+ cells). Moreover, there was a positive correlation between expression of the p53 protein and of the Ki-67 antigen in histologic types of B cell lymphomas and of T cell lymphomas, respectively, except in small non-cleaved (Burkitt's) and lymphoblastic types. Therefore, sporadic cases showing p53+ cells > Ki-67+ cells revealed alteration of the p53 gene, and expressed abnormal p53 protein (mutant form). Most cases showing p53+ cells < Ki-67+ cells expressed normal p53 protein (wild type), and may reflect the rapid proliferation rate.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Genes p53/genética , Antígeno Ki-67/metabolismo , Linfoma no Hodgkin/genética , Mutación Puntual , Proteína p53 Supresora de Tumor/metabolismo , Secuencia de Bases , Cartilla de ADN/química , ADN de Neoplasias/análisis , Humanos , Inmunohistoquímica , Linfoma no Hodgkin/metabolismo , Datos de Secuencia Molecular , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADN

RESUMEN

The disposition of theophylline (aminophylline) administered either parenterally or orally to anesthetized dogs was studied. Pharmacokinetics of theophylline (8.2 mg/kg, n = 10) following intravenous administration could be analyzed by a two-compartment open model. The half-time (T1/2 beta) of theophylline was 5.63 +/- 0.83 hr, and the volume of distribution (Vd) was 0.73 +/- 0.04 l/kg. The elimination rate constant was 0.37 +/- 0.05 hr-1. Two metabolites of theophylline were isolated from urine and identified as 3-methyl xanthine (3-MX) and 1,3-dimethyl uric acid (1,3-DMU) by HPLC. The dogs excreted about 85% (n = 4) of the dose in urine in 24 hr. The majority (2/3) was excreted as changed theophylline, i.e., 3-MX 40.2 +/- 3.5% and 1,3-DMU 26.2 +/- 4.3%, while unchanged theophylline amounted to 18.2 +/- 2.4%. Absorption of theophylline (8.2 mg/kg, n = 5) administered intramuscularly was good as indicated by its high bioavailability (101.9 +/- 6.5%), but the value of bioavailability was low in oral administration (72.8 +/- 11.8%, n = 5). The percentage of protein binding (about 44%, n = 3-7) did not change by increasing the serum concentration (8.2-24.6 micrograms/ml).

Asunto(s)

Teofilina/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Perros , Femenino , Inyecciones Intramusculares , Inyecciones Intravenosas , Masculino , Modelos Biológicos , Unión Proteica , Teofilina/administración & dosificación

Asunto(s)

Serratia marcescens/aislamiento & purificación , Antibacterianos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Serratia marcescens/efectos de los fármacos

Asunto(s)

Bacillus/aislamiento & purificación , Infecciones Bacterianas/microbiología , Sepsis/microbiología , Anciano , Femenino , Humanos , Factores de Tiempo