RESUMO
The dephasing of the Fermi edge singularity excitations in two modulation doped single quantum wells of 12 nm and 18 nm thickness and in-well carrier concentration of â¼4 × 10(11) cm(-2) was carefully measured using spectrally resolved four-wave mixing (FWM) and two-dimensional Fourier transform (2DFT) spectroscopy. Although the absorption at the Fermi edge is broad at this doping level, the spectrally resolved FWM shows narrow resonances. Two peaks are observed separated by the heavy hole/light hole energy splitting. Temperature dependent "rephasing" (S1) 2DFT spectra show a rapid linear increase of the homogeneous linewidth with temperature. The dephasing rate increases faster with temperature in the narrower 12 nm quantum well, likely due to an increased carrier-phonon scattering rate. The S1 2DFT spectra were measured using co-linear, cross-linear, and co-circular polarizations. Distinct 2DFT lineshapes were observed for co-linear and cross-linear polarizations, suggesting the existence of polarization dependent contributions. The "two-quantum coherence" (S3) 2DFT spectra for the 12 nm quantum well show a single peak for both co-linear and co-circular polarizations.
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We investigated the optical properties of 4,4'-stilbenedinitrene at low temperature and in high magnetic fields and compared the results with complementary first principles calculations. Both physical tuning parameters allow us to manipulate the singlet-triplet equilibrium, and by doing so, control the optical contrast (which is on the order of -2.5 × 10(2) cm(-1) at 555 nm and 35 T). Moreover, analysis of the magneto-optical response using a combined population and Beer's law framework reveals the singlet-triplet spin gap and identifies particular features in the absorption difference spectrum as deriving from singlet or triplet state excitations. These findings deepen our understanding of coupling in open shell molecules and show how chemical structure modification can modulate charge-spin interactions in organic biradicals.
Assuntos
Campos Magnéticos , Estilbenos/química , Estrutura Molecular , TemperaturaRESUMO
Cytomegalovirus (CMV) reinfection of seropositive individuals has been associated with adverse outcomes in organ transplantation and is a frequent cause of congenital infection. Previously we demonstrated that mismatching of CMV glycoprotein H (gH) serotypes was associated with CMV disease after renal transplantation. Because the antigen domain 2 (AD2) epitope of glycoprotein B (gB) is conserved among CMV isolates and is one of the known targets of neutralizing antibodies, in this study we investigated whether antibodies against the epitope contribute to protection from CMV reinfection in renal transplantation, irrespective of gH serological matching. For this purpose, the gB and gH serology and clinical outcomes were analyzed retrospectively for 77 transplant recipients in the donor positive/recipient positive setting, who were managed by preemptive strategy. We found that there was a good negative correlation between the numbers of antigenemia-positive cells and the levels of antibodies against gB AD2 in the CMV-gH antibody matched group, but not in the CMV-gH antibody mismatched group. None of the recipients with antibodies against both gB AD2 and strain-specific epitopes of gH have experienced CMV disease during 6 month after transplantation, while 28% of those who lacked either/both antibody response needed preemptive therapy. Because the outcome was statistically significant, antibodies against gB AD2 can be a useful indicator to predict emergence of CMV disease for preemptive therapy, in addition to antibodies against the mismatched gH types.
Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Infecções por Citomegalovirus/imunologia , Epitopos/imunologia , Transplante de Rim/efeitos adversos , Proteínas do Envelope Viral/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/química , Citomegalovirus/classificação , Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Epitopos/genética , Humanos , Transplante de Rim/imunologia , Sorotipagem , Especificidade da Espécie , Doadores de Tecidos , Proteínas do Envelope Viral/químicaRESUMO
We investigated the tunability of the singlet-triplet equilibrium population in the organic biradical 1,4-phenylenedinitrene via magneto-optical spectroscopy. A rich magnetochromic response occurs because applied field increases the concentration of the triplet state species, which has a unique optical signature by comparison with the singlet biradical and the precursor molecule. A Curie-like analysis of the magneto-optical properties allows us to extract the spin gap, which is smaller than previously supposed. These measurements establish the value of local-probe photophysical techniques for magnetic property determination in open-shell systems such as biradicals where a traditional electron paramagnetic resonance Curie law analysis has intrinsic limitations.
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Immediately before the transition from metaphase to anaphase, the protein kinase activity of maturation or M-phase promoting factor (MPF) is inactivated by a mechanism that involves the degradation of its regulatory subunit, cyclin B. The availability of biologically active goldfish cyclin B produced in Escherichia coli and purified goldfish proteasomes (a nonlysosomal large protease) has allowed the role of proteasomes in the regulation of cyclin degradation to be examined for the first time. The 26S, but not the 20S proteasome, digested recombinant 49-kD cyclin B at lysine 57 (K57), producing a 42-kD truncated form. The 42-kD cyclin was also produced by the digestion of native cyclin B forming a complex with cdc2, a catalytic subunit of MPF, and a fragment transiently appeared during cyclin degradation when eggs were released from metaphase II arrest by egg activation. Mutant cyclin at K57 was resistant to both digestion by the 26S proteasome and degradation at metaphase/anaphase transition in Xenopus egg extracts. The results of this study indicate that the destruction of cyclin B is initiated by the ATP-dependent and ubiquitin-independent proteolytic activity of 26S proteasome through the first cutting in the NH2 terminus of cyclin (at K57 in the case of goldfish cyclin B). We also surmise that this cut allows the cyclin to be ubiquitinated for further destruction by ubiquitin-dependent activity of the 26S proteasome that leads to MPF inactivation.
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Ciclinas/metabolismo , Complexos Multienzimáticos/metabolismo , Oócitos/enzimologia , Sequência de Aminoácidos , Animais , Extratos Celulares/química , Extratos Celulares/fisiologia , Ciclinas/genética , Citoplasma/enzimologia , Escherichia coli/genética , Feminino , Carpa Dourada , Metáfase/fisiologia , Dados de Sequência Molecular , Ubiquitinas/metabolismo , Xenopus laevisRESUMO
Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6-12 months, respectively. At 6-12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.
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Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/patologia , Rejeição de Enxerto/patologia , Transplante de Rim , Rim/patologia , Adulto , Biópsia , Incompatibilidade de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos/imunologia , Complemento C4b/metabolismo , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Rim/metabolismo , Transplante de Rim/imunologia , Transplante de Rim/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Sarcoidosis is a chronic systemic disease that is characterized by the formation of noncaseating granuloma and whose etiology is unclear. It is unclear whether patients with sarcoidosis are suitable organ donors. CASE: We treated a 56-year-old woman with pulmonary sarcoidosis who donated her kidney. She was previously in good health and was diagnosed with pulmonary sarcoidosis during her preoperative examination. Because she presented with no symptoms and was otherwise in good condition, donor nephrectomy was performed. RESULTS: Baseline biopsy examination showed no evidence of sarcoidosis. One year after transplantation, both the donor and the recipient had not developed kidney dysfunction or recurrence of sarcoidosis. CONCLUSION: This is a rare case in which a patient with pulmonary sarcoidosis donated a kidney for transplantation, and both the recipient and the donor were clinically healthy. A patient with sarcoidosis and no kidney lesion can donate a living kidney, because transplantation appears to be safe for both the recipient and the donor.
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Transplante de Rim , Doadores Vivos , Sarcoidose Pulmonar , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: An equation for the estimated glomerular filtration rate (eGFR) is generally used for evaluating renal function in Japan. OBJECTIVE: To assess the accuracy of the preoperative eGFR for estimating kidney donors' measured glomerular filtration rate (mGFR). METHODS: Between April 2009 and August 2014, 91 Japanese living kidney donors were included in this study. The eGFR was calculated as follows: eGFR = 194 × serum creatinine(-1.094) × Age(-0.287) (and × 0.739 for women), and the mGFR was evaluated using inulin clearance. The preoperative eGFR was then compared with the mGFR. RESULTS: Patients included 27 men and 64 women with a mean age of 56.8 ± 9.5 years (range, 36-79 years), mean body surface area of 1.56 ± 0.14 m(2) (range 1.27-1.92 m(2)), mean body mass index of 22.3 ± 2.3 kg/m(2) (range 14.0-27.0 kg/m(2)), and mean serum creatinine level of 0.66 ± 0.14 mg/dL (range 0.39-0.97 mg/dL). The mean eGFR was 81.3 ± 14.2 mL/min/1.73 m(2) (range 45.5-125.9 mL/min/1.73 m(2)), and the mean mGFR was 89.0 ± 15.5 mL/min/1.73 m(2) (range 45.4-130.7 mL/min/1.73 m(2)). The eGFR was significantly lower than the mGFR (P < .001). The correlation coefficient for the relationship between the eGFR and mGFR values was 0.503, and the mean difference between the 2 values was -7.8 (8.7%). CONCLUSIONS: Although the eGFR correlated with the mGFR, the eGFR values did not accurately estimate the mGFR in living kidney donors. Therefore, it is necessary to evaluate the mGFR, especially in marginal kidney donors.
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Taxa de Filtração Glomerular , Transplante de Rim , Doadores Vivos , Adulto , Idoso , Creatinina/sangue , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Cuidados Pré-OperatóriosRESUMO
Destruction of cyclin B is required to the mitotic and meiotic cycles. A cyclin-specific ubiquitinating system, including ubiquitin-activating enzyme (E1), is thought to be responsible for cyclin B destruction. Here we present the cloning, sequencing and expression analysis of goldfish, Carassius auratus, E1 from goldfish ovary. The cloned cDNA is 4069 bp long and encodes 1059 amino acids. The deduced amino acid sequence is highly homologous to E1 from other species. Recombinant goldfish E1 could transfer ubiquitin to cyclin-selective ubiquitin-conjugating enzyme. Tissue distribution revealed a single 4.0-kb message ubiquitous among tissues.
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Carpa Dourada/genética , Ligases/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Clonagem Molecular , DNA Complementar/análise , Expressão Gênica , Humanos , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Enzimas Ativadoras de Ubiquitina , Ubiquitina-Proteína LigasesRESUMO
The proteasome is an essential component of the proteolytic pathway in eukaryotic cells and is responsible for the degradation of most cellular proteins. Proteasomes are sorted into two types, 20S and 26S. The 20S proteasome forms the catalytic core of the 26S proteasome. The 26S proteasome is involved in the ubiquitin-dependent protein degradation pathway. Cyclins and cdk inhibitors or c-mos products, proteins critical to the regulation of the cell cycle, are known to be degraded by the ubiquitin pathway. Thus the 26S proteasome is thought to be involved in the regulation of cell cycle events. This review focuses on advances in the study of the biochemical properties and functions of the 20S and 26S proteasomes in the fish meiotic cell cycle.
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Cisteína Endopeptidases/fisiologia , Peixes/crescimento & desenvolvimento , Peixes/metabolismo , Complexos Multienzimáticos/fisiologia , Oócitos/enzimologia , Oócitos/crescimento & desenvolvimento , Animais , Cumarínicos/metabolismo , Feminino , Meiose/fisiologia , Modelos Biológicos , Oligopeptídeos/metabolismo , Oogênese/fisiologia , Peptídeo Hidrolases/fisiologia , Complexo de Endopeptidases do Proteassoma , Especificidade por Substrato , Ubiquitinas/metabolismoRESUMO
In city area, there are several types of electromagnetic noises originated in daily activities of human beings. The noises possibly cause difficulty to detect geomagnetic and geoelectric signatures. It is important for investigators who are studying geomagnetic effects for biology, medicine and so on to be aware that such noises are present in city area. Among these noises, the one due to electric railways driven by direct-current electric power supply might give the largest influence because this type of noise continues almost all the time and have complex wave forms. The characteristics of the noises are briefly introduced by showing a theoretical background and some experimental studies.
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Campos Eletromagnéticos/efeitos adversos , Eletricidade , Centrais Elétricas , FerroviasRESUMO
The proteasomes are large, multi-subunit particles that act as the proteolytic machinery for most of the regulated intracellular protein degradation in eukaryotic cells. To investigate the regulatory mechanism for the 26S proteasome in cell-cycle events, we purified this proteasome from immature and mature oocytes, and compared its subunits. Immunoblot analysis of 26S proteasomes showed a difference in the subunit of the 20S proteasome. A monoclonal antibody, GC3beta, cross-reacted with two bands in the 26S proteasome from immature oocytes (in G2-phase); however, the upper band was absent in the 26S proteasome from mature oocytes (in M-phase). These results suggest that changes in the subunits of 26S proteasomes are involved in the regulation of the meiotic cell cycle. Here we describe the molecular cloning of one of the alpha subunits of the 20S proteasome from a Xenopus ovarian cDNA library using an anti-GC3beta monoclonal antibody. From the screening, two types of cDNA are obtained, one 856bp, the other 984bp long. The deduced amino-acid sequences comprise 247 and 248 residues, respectively. These deduced amino-acid sequences are highly homologous to those of alpha4 subunits of other vertebrates. Phosphatase treatment of 26S proteasome revealed the upper band to be a phosphorylated form of the lower band. These results suggest that a part of the alpha4 subunit of the Xenopus 20S proteasome, alpha4_xl, is phosphorylated in G2-phase and dephosphorylated in M-phase.
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Cisteína Endopeptidases/genética , Meiose/genética , Complexos Multienzimáticos/genética , Xenopus laevis/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Ciclo Celular/genética , Cisteína Endopeptidases/análise , DNA Complementar/química , DNA Complementar/genética , DNA Complementar/isolamento & purificação , Feminino , Dados de Sequência Molecular , Complexos Multienzimáticos/análise , Oócitos/enzimologia , Oócitos/crescimento & desenvolvimento , Peptídeo Hidrolases/análise , Complexo de Endopeptidases do Proteassoma , Isoformas de Proteínas/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
Destruction of cyclin B is required for exit from mitosis and meiosis. A cyclin-specific ubiquitinating system, including cyclin-selective ubiquitin carrier protein (E2-C), is thought to be responsible for cyclin B destruction. Here we present the cloning, sequencing and expression analysis of goldfish, Carassius auratus, E2-C which encodes the cyclin-selective ubiquitin carrier protein from goldfish ovary. The cloned cDNA is 677 bp long and encodes 172 amino acids. The deduced amino acid sequence is highly homologous to E2-C from other species. Recombinant goldfish E2-C possesses ubiquitinating activity against cyclin B. The expression of mRNA for E2-C was similar to that of mRNA for cyclin B, occurring at very high level in the ovary. The similarity of the expression pattern of E2-C and cyclin B suggests that E2-C mediates a cyclin-specific ubiquitination.
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Proteínas de Transporte/genética , Carpa Dourada/genética , Ligases , Enzimas de Conjugação de Ubiquitina , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Transporte/química , Clonagem Molecular , Ciclina B/genética , Ciclina B/metabolismo , DNA Complementar/genética , Escherichia coli , Regulação da Expressão Gênica , Dados de Sequência Molecular , RNA Mensageiro/metabolismo , Proteínas Recombinantes/química , Homologia de Sequência de AminoácidosRESUMO
Proteasomes are large, multisubunit particles that act as the proteolytic machinery for most of the regulated intracellular protein breakdown in eukaryotic cells. Proteasomes are present in both the nucleus and cytoplasm. When we analyzed the molecular composition of protein constituents of the nuclear matrix preparation of goldfish oocytes by two-dimensional polyacrylamide gel electrophoresis followed by sequence analysis, we found a 26 kDa spot identical in amino acid sequence to the beta6 subunits of the 20S proteasome. No spot of other subunits of 20S proteasome was detected. Here we describe the cloning, sequencing and expression analysis of Carassius auratus, beta6_ca, which encodes one of the proteasome beta subunits from goldfish ovary. From the screening of an ovarian cDNA library, two types of cDNA were obtained, one 941 bp and the other 884 bp long. The deduced amino acid sequences comprise 239 and 238 residues, respectively. These deduced amino acid sequences are highly homologous to those of beta6 subunits of other vertebrates. Immunoblot analysis of nuclear matrix using anti-proteasome antibodies showed only a spot of beta6_ca. These results suggest that the beta6 subunit of the goldfish 20S proteasome, beta6_ca, is responsible for anchoring proteasomes in the nucleus.
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Cisteína Endopeptidases/química , Complexos Multienzimáticos/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Domínio Catalítico , Clonagem Molecular , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/isolamento & purificação , Eletroforese em Gel Bidimensional , Carpa Dourada , Immunoblotting , Dados de Sequência Molecular , Peso Molecular , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/isolamento & purificação , Matriz Nuclear/química , Oócitos , Complexo de Endopeptidases do Proteassoma , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de AminoácidosRESUMO
BACKGROUND: Most investigations have revealed that the improvement in early graft survival has not resulted in a corresponding improvement in long-term graft survival. The risk factors for long-term graft survival should be clarified. METHODS: A single-center experience of 1100 consecutive renal transplant recipients who received kidneys from living donors from 1983 to 1998 was reviewed to clarify the time dependency of risk factors for long-term graft survival. We examined various possible risk factors, including HLA-AB and -DR mismatches, ABO-blood group incompatibility, graft weight, donor age and sex, recipient age and sex, and the presence or absence of acute rejection by using the time-dependent, nonproportional Cox's hazards model. RESULTS: Acute rejection episode, donor age, HLA-AB 4-antigen mismatches, ABO-incompatible transplantation, smaller kidney weight compared with the patient's body weight (Kw/Bw ratio less than 2.67), and transplantation from an unrelated living donor were risk factors for long-term graft outcome. Multivariate analysis for time-dependent risk factors showed that donor age of more than 60 years was the most important risk factor for long-term graft failure after 5 years posttransplantation (hazard ratio: 2.57). In contrast, acute rejection, ABO incompatibility, and nonrelated donors were significant risk factors for short-term graft failure within 5 years after kidney transplantation (hazard ratios: 2.68, 1.57, and 1.69, respectively). CONCLUSIONS: Donor age of more than 60 years was a crucial risk factor affecting long-term graft survival. In contrast, acute rejection, ABO incompatibility, and nonrelated donors were significant risk factors for short-term graft failure.
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Transplante de Rim/efeitos adversos , Sistema ABO de Grupos Sanguíneos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Lactente , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Doadores de TecidosRESUMO
BACKGROUND: Our previous studies showed that the incidence of humoral rejection was extremely high in ABO-incompatible living kidney transplantation. This result suggests that anti-A/B antibody titers directly influence the graft survival of ABO-incompatible kidney transplantation. In this study, we examined the impact of preoperative anti-A/B antibody titers on the results of ABO-incompatible living kidney transplantation. METHODS: Sixty-seven patients underwent ABO-incompatible living kidney transplantation at our institution between January 1989 and December 1995. The mean age was 34.9 years with 38 males and 29 females. Sixty-one of the 67 recipients were included in an analysis of the impact of anti-A/B antibody titer in long-term graft survival. The remaining six patients were excluded because of death with a functioning graft (three patients) and withdrawal of immunosuppression due to nonimmunological reasons (three patients) within 1 year after renal transplantation. RESULTS: The graft survival rate for the level of less than 1:16 in maximum IgG antibody before transplantation (n=21) at 1, 5, and 8 years was 81.0, 66.8, and 66.8%, respectively. The corresponding values for the level of 1:32-1:64 (n=33) and higher than 1:128 (n=7) were 93.9, 90.5, and 79.7%, and 42.9, 28.6, and 28.6%, respectively (log-rank test, P=0.0007). There was no significant association between maximum anti-A/B IgM titers, minimum anti-A/B IgM titers, minimum anti-A/B IgG titers, and graft survival. CONCLUSIONS: Preoperative maximum anti-A/B IgG titers correlated with the long-term graft survival in ABO-incompatible living kidney transplantation. Thus, preoperative maximum levels of anti-A/B IgG titers are one of the good predictors of the results of ABO-incompatible living kidney transplantation.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos , Isoanticorpos/fisiologia , Transplante de Rim/imunologia , Adolescente , Adulto , Criança , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Early diagnosis of cytomegalovirus (CMV) infection, which is an important cause of morbidity and mortality in renal transplant recipients, remains of great importance. This prospective study was performed in kidney transplant recipients to determine the diagnostic value of the CMV antigenemia assay in comparison with polymerase chain reaction (PCR), serology, and shell vial assay. METHODS: Seventy-five consecutive renal transplant recipients were enrolled in this study and monitored by both antigenemia assay and serology. The initial 34 of the 75 patients were subjected to PCR and shell vial assay. RESULTS: Antigenemia, PCR, and shell vial assay became positive before the onset of CMV-related symptoms in 31/34 (89%), 13/16 (81%), and 2/16 (13%), respectively. None of the 34 patients who had symptomatic CMV disease showed a significant increase in IgG or IgM before the onset of symptoms. Antigenemia and PCR assays turned positive, 7 and 11 days (median), respectively, before the onset of clinical symptoms. Serology and shell vial assay became positive 21 and 25 days (median), respectively, after the onset of CMV-related clinical symptoms. To examine the clinical value of these assays, "good correlation" was defined based on the correlation between the clinical course and the results of the assays. Good correlation with the antigenemia assay was observed in 33 (96%) out of 34 renal transplant recipients who recovered from their CMV disease after ganciclovir therapy. Only one of 16 (7%) patients showed good correlation by shell vial assay, whereas PCR and serology did not show a good correlation. Consequently, antigenemia was considered the best way to monitor CMV infections after kidney transplantation. CONCLUSIONS: Only the CMV antigenemia assay can be successfully employed after renal transplantation for the early diagnosis and extensive monitoring of active CMV infection.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Transplante de Rim , Adolescente , Adulto , Antígenos Virais/análise , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Testes Sorológicos , Fatores de TempoRESUMO
BACKGROUND: One of the most serious problems facing major transplant programs is the severe shortage of organs. Expansion of the donor pool to include nontraditional donors, such as non-heart-beating donors (NHBDs), would considerably expand the availability of organs. METHODS: Between 1983 and 1996, we performed a total of 125 non-heart-beating cadaveric renal transplantations under cyclosporine-based or tacrolimus-based immunosuppression. Thirty-nine recipients were females and 86 were males. Total ischemic time (TIT) and warm ischemic time (WIT) were an average of 761+/-347 min (322-2027 min) and 7.4+/-13.1 min (0-45 min), respectively. RESULTS: Of the 125 transplanted kidneys from NHBDs, 98 (78.4%) developed delayed graft function (DGF), which lasted a mean of 16+/-21 days (range 3-37 days). One hundred and eight patients (86.4%) were off dialysis by the time of discharge. Of the 125 grafts, 11 (8.8%) were primary nonfunction. The average of the nadir of serum creatinine levels, which was evaluated using 108 patients who were off dialysis by the time of discharge, was 1.4+/-0.5 mg/dl. The lowest creatinine levels (nadir) were under 2.0 mg/dl in 98 (78.4%) of the 125 patients. Acute rejection occurred in 64 (51.2%) of the 125 recipients. Patient survival rates were 90% at 5 years and 88% at 10 years. Graft survival rates were 65% at 5 years and 46% at 10 years. We tried to find the risk factors that affected graft survival. We examined the various possible risk factors, including harvesting condition (controlled versus uncontrolled), HLA-AB mismatches, HLA-DR mismatches, graft weight, donor age and sex, recipient age and sex, posttransplant DGF, acute rejection, WIT, and TIT. However, no significant risk factor was identified except acute rejection. We tried to discover the risk factors that caused primary nonfunction. Possible risk factors, including donor age, TIT, WIT, graft weight, and harvesting condition were compared, but no significant risk factor was identified. Long-term renal function was evaluated by serum creatinine levels. Serum creatinine levels at 1, 5, and 10 years were 1.76+/-0.7 mg/dl, 1.7+/-0.96 mg/dl, and 1.53-/+0.6 mg/dl, respectively. CONCLUSIONS: In conclusion, our data demonstrated that the procurement of kidneys from NHBDs leads to acceptable long-term graft survival and renal function, despite a high incidence of DGF.
Assuntos
Transplante de Rim , Rim/fisiopatologia , Doadores de Tecidos , Adulto , Idoso , Feminino , Sobrevivência de Enxerto , Coração/fisiologia , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transplante HomólogoRESUMO
BACKGROUND: Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT. METHODS: Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases. RESULTS: Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos , Transplante de Rim/imunologia , Obtenção de Tecidos e Órgãos , Imunologia de Transplantes , Adolescente , Adulto , Criança , Feminino , Histocompatibilidade , Humanos , Imunoadsorventes , Terapia de Imunossupressão , Japão , Falência Renal Crônica/cirurgia , Funções Verossimilhança , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Plasmaferese , Transplantes/provisão & distribuiçãoRESUMO
The specificity of action of the proteasome purified from the cytosol of Xenopus oocyte was investigated using oxidized insulin B chain as the substrate. HPLC analyses of the produced peptides followed by amino acid analyses showed that it cleaved four peptide bonds, Leu6-Cya7, Glu13-Ala14, Leu15-Tyr16, and Leu17-Val18, of the peptide. Cleavage at Leu6-Cya7 was found to be specific to the Xenopus enzyme. The enzyme did not cleave Gln4-His5 and Cya19-Gly20, which are commonly hydrolyzed by proteasomes from rat and mouse liver, and human erythrocyte. In contrast to previous results obtained with the mammalian proteasome, the cleavage by the Xenopus enzyme was inhibited selectively by chymostatin. These results demonstrate distinct species difference in cleavage specificity and inhibition profile among proteasomes of different origins.