RESUMO
The gene for ATP binding cassette subfamily A member 2 (ABCA2) is located at chromosome 9q34.3. Biallelic ABCA2 variants lead to intellectual developmental disorder with poor growth and with or without seizures or ataxia (IDPOGSA). In this study, we identified novel compound heterozygous ABCA2 variants (NM_001606.5:c.[5300-17C>A];[6379C>T]) by whole exome sequencing in a 28-year-old Korean female patient with intellectual disability. These variants included intronic and nonsense variants of paternal and maternal origin, respectively, and are absent from gnomAD. SpliceAI predicted that the intron variant creates a cryptic acceptor site. Reverse transcription-PCR using RNA extracted from a lymphoblastoid cell line of the patient confirmed two aberrant transcripts. Her clinical features are compatible with those of IDPOGSA.
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Deficiência Intelectual , Humanos , Feminino , Adulto , Deficiência Intelectual/genética , Mutação , Família , Síndrome , Ataxia/genéticaRESUMO
For the practical application of fuel cells in vehicles, it is a challenge to develop a proton solid electrolyte that coexhibits thermal stability and high proton conductivity at wide intermediate temperatures. Here, we report on the tunnel structured phosphate KNi1-xH2x(PO3)3·yH2O, which exhibits high proton conductivity at room temperature up to 500 °C, with the conductivity value reaching 1.7 × 10-2 S cm-1 at 275 °C for x = 0.18. This material, composed of the smallest cations that form the tunnel framework with face-shared (KO6) and (NiO6) chains and PO4 tetrahedral chains, retained the rigid framework up to 600 °C. Two oxygen sites of water molecules located adjacent to each other along the PO4 tetrahedral chains in the tunnel provided the proton conduction pathway. The sample maintained a conductivity of 5.0 × 10-3 S cm-1 for 10 h at 150 °C while changing the measurement atmosphere to a N2 gas flow, a 4% H2-96% Ar gas flow, and an O2 gas flow. The conductivity value at x = 0.18 obtained from the DC measurement was in the order of 10-6 S cm-1, close to the instrument's measurement limit. These results demonstrate that tunnel phosphate has potential as a proton solid electrolyte for next-generation fuel cells.
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AFF3 at 2q11.2 encodes the nuclear transcriptional activator AF4/FMR2 Family Member 3. AFF3 constitutes super elongation complex like 3, which plays a role in promoting the expression of genes involved in neurogenesis and development. The degron motif in AFF3 with nine highly conserved amino acids is recognized by E3 ubiquitin ligase to induce protein degradation. Recently, AFF3 missense variants in this region and variants featuring deletion including this region were identified and shown to cause KINSSHIP syndrome. In this study, we identified two novel and one previously reported missense variants in the degron of AFF3 in three unrelated Japanese patients. Notably, two of these three variants exhibited mosaicism in the examined tissues. This study suggests that mosaic variants also cause KINSSHIP syndrome, showing various phenotypes.
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Células Germinativas , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Fenótipo , Proteínas NuclearesRESUMO
AIM: The 2011 Great East Japan Earthquake (GEJE) was a disaster leading to radiation exposure and psychological distress, particularly among pregnant women. However, it is not known how this affected the seasonal changes of pregnancy and childbirth. Therefore, this study investigated the impact of the GEJE in the Fukushima Prefecture on spontaneous and induced abortions with regard to seasonal variability. METHODS: We used the data of vital statistics of live birth and stillbirth registry and the census survey of the Fukushima Maternity Care Facility. We calculated the spontaneous and induced abortion rate for 2011-2016 using two different methods (cross-sectional and longitudinal). We calculated the quartiles and outliers to determine the impact and duration of the GEJE. Periodicity was investigated using spectral density analysis. The data were analyzed for the entire Fukushima Prefecture and by region. RESULTS: The spontaneous abortion rate did not show specific changes after the GEJE. Contrarily, the monthly analysis in the cross-sectional method, revealed specific increases in induced abortion rate during the year after the GEJE; in the longitudinal method, induced abortions increased among women who became pregnant within 1 year after the GEJE. Spontaneous abortion showed no specific periodicity, while induced abortion showed cycles of 6 and 12 months, with a particular increase in May each year. CONCLUSIONS: The spontaneous abortion rate was not affected by the GEJE. The changes in the induced abortion rate after the disaster may have overlapped with the timing of the increased periodicity, and cannot be attributed solely to the GEJE.
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Aborto Induzido , Aborto Espontâneo , Terremotos , Acidente Nuclear de Fukushima , Serviços de Saúde Materna , Estatísticas Vitais , Feminino , Gravidez , Humanos , Estudos Longitudinais , Japão , Estudos Transversais , CensosRESUMO
Double rupture is a very rare, and life-threatening complication after acute myocardial infection (AMI), which defined as the coexistence of any two of the three types of rupture include left ventricular free wall repture (LVFWR), ventricular septal perforation (VSP) and papillary muscule repture (PMR). We report here a case of successful staged repair of double rupture combined LVFWR and VSP. A 77-year-old woman with diagnosis of AMI in the anteroseptal area fell into cardiogenic shock suddenly just before starting coronary angiography. Echocardiography showed left ventricular free wall rupture, then an emergent operation was performed under intraaortic balloon pumping (IABP) and percutaneous cardiopulmonary support (PCPS) assistance using bovine pericardial patch and felt sandwich technique. Intraoperative transesophageal echocardiography revealed ventricular septal perforation on the apical anterior wall. Her hemodynamic condition was stable, therefore we selected a staged VSP repair to avoid surgery on freshly infarcted myocardium. Twenty-eight days after the initial operation, VSP repair was performed using the extended sandwich patch technique via right ventricle incision. Postoperative echocardiography revealed no residual shunt.
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Ruptura Cardíaca , Infarto do Miocárdio , Ruptura do Septo Ventricular , Humanos , Feminino , Animais , Bovinos , Idoso , Ruptura do Septo Ventricular/diagnóstico por imagem , Ruptura do Septo Ventricular/etiologia , Ruptura do Septo Ventricular/cirurgia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/cirurgia , Ruptura Cardíaca/diagnóstico por imagem , Ruptura Cardíaca/etiologia , Ruptura Cardíaca/cirurgia , Choque Cardiogênico , Angiografia CoronáriaRESUMO
A 38-year-old male, he was diagnosed with a giant pulmonary bulla occupying 2/3 of the right thoracic cavity on chest computed tomography( CT). The preoperative pulmonary function was unfavorable, so bullectomy of right upper lobe with video-assisted thoracoscopic surgery( VATS) was performed. The outpatient follow-up was completed at 6 months after surgery. However, one year and eleven months postoperatively, the patient returned to the clinic complaining of dyspnea. Chest X-ray and CT showed a recurrence of a giant emphysematous bulla in the right upper lobe. Two years and three months after the initial surgery, the recurrent giant bulla was resected by right upper lobectomy with VATS. About four years after the reoperation, no recurrence of giant pulmonary bulla has been seen. Although there are some reports on surgical treatment and results of giant pulmonary bulla, there are few reports on recurrent cases, so we report this case.
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Pneumopatias , Enfisema Pulmonar , Masculino , Humanos , Adulto , Vesícula/diagnóstico por imagem , Vesícula/cirurgia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/cirurgia , Pulmão/cirurgiaRESUMO
A 79-year-old male patient underwent esophagogastroduodenoscopy, which revealed a reddish lesion, 10mm in diameter, presenting as a surface recess in the angular incisure. He was diagnosed with gastric follicular lymphoma. Positron emission tomography-computed tomography revealed metastasis to the mediastinal lymph node, although the tumor size was small. Hence, we did not administer any treatment and continued following up. After 8 months, multiple enlarged lymphoma lesions in the stomach and a mass with ulceration on the oral side of the duodenal papilla were observed. The tumor had transformed into diffuse large B-cell lymphoma; therefore, chemotherapy was initiated. The patient has remained recurrence-free for 55 months after treatment.
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Linfoma Folicular , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Masculino , Humanos , Idoso , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/tratamento farmacológico , Linfoma não Hodgkin/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Estômago/patologiaRESUMO
OBJECTIVE: To examine the safety and efficacy of microwave tissue coagulation (MTC) for prostate cancer and assess its use in lesion-targeted focal therapy in a non-clinical study and a clinical phase II trial. METHODS: In the non-clinical study using Microtaze® -AFM-712 (Alfresa Pharma Corporation, Osaka, Japan) with an MTC needle, MTC was performed using a transperineal approach to targeted canine prostatic tissue under real-time ultrasonography guidance. Using various MTC output and irradiation time combinations, the targeted and surrounding tissues (rectum, bladder and fat) were examined to confirm the extent of coagulative necrosis or potential cell death, and to compare intra-operative ultrasonography and pathology findings. The exploratory clinical trial was conducted to examine the safety and efficacy of MTC. Five selected patients underwent transperineal MTC to clinically single lesion magnetic resonance imaging (MRI)-visible lesions with Gleason score 3 + 4 or 4 + 4. Prostate-specific antigen (PSA), MRI and Expanded Prostate Cancer Index Composite questionnaire findings were compared before and 6 months after surgery. RESULTS: The region of coagulative necrosis was predictable by monitoring of ultrasonically visible vaporization; thus, by placing the MTC needle at a certain distance, we were able to perform a safe procedure without adverse events affecting the surrounding organs. Based on the non-clinical study, which used various combinations of output and irradiation time, MTC with 30-W output for 60-s irradiation was selected for the prostate. Based on the predictable necrosis, the therapeutic plan (where to place the MTC needle to achieve complete ablation of the target and how many sessions) was strictly determined per patient. There were no serious adverse events in any patient and only temporary urinary symptoms related to MTC therapy were observed. Furthermore, post-treatment satisfaction was very high. All preoperative MRI-visible lesions disappeared, and PSA decreased by 55% 6 months after surgery. CONCLUSION: Microwave tissue coagulation may be an option for lesion-targeted focal therapy for prostate cancer.
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Antígeno Prostático Específico , Neoplasias da Próstata , Humanos , Masculino , Animais , Cães , Micro-Ondas/uso terapêutico , Estudos Prospectivos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , NecroseRESUMO
A 57-year-old man with fatigue was admitted to our hospital. Abdominal contrast computed tomography indicated the presence of a 35mm tumor in the pancreatic head and dilation of the main pancreatic duct from its body to the tail. Endoscopic ultrasonography revealed that the tumor had infiltrated and occupied the main pancreatic duct, and endoscopic retrograde pancreatography confirmed that the tumor was present in the main pancreatic duct. Tumor biopsy via endoscopic retrograde cholangiopancreatography demonstrated the proliferation of spindle and pleomorphic cells. Therefore, the patient was diagnosed with anaplastic pancreatic carcinoma and underwent subtotal stomach-preserving pancreaticoduodenectomy. Histological analysis showed the prevalence of adenocarcinoma and anaplastic carcinoma cells in the pancreatic parenchyma and main pancreatic duct, respectively. Anaplastic carcinoma cells showed a decrease in E-cadherin staining. In conclusion, tumor cell proliferation and lack of cell adhesion may have caused the infiltration into the main pancreatic duct.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias PancreáticasRESUMO
Ischemia-reperfusion (I/R) is associated with various pathogenic conditions, and there has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non-blanchable erythema. Several studies demonstrated that oxidative stress is a key player in I/R injury, and the inhibition of oxidative stress may be capable of protecting tissue damage after I/R injury in various organs including skin. Dimethyl fumarate (DMF) approved by the Food and Drug Administration is Nrf2 activator, and recent studies revealed the antioxidative and anti-inflammatory effects of DMF on I/R injury in animal models. Our objective was to assess the effects of oral administration of DMF on the development of PUs after cutaneous I/R injury in mice. We found that DMF administration significantly decreased the size of PUs after cutaneous I/R. Cutaneous I/R-induced oxidative stress was also significantly inhibited by DMF in OKD48 mice, in which oxidative stress can be visually assessed. In addition, DMF treatment decreased hypoxic area, the numbers of apoptotic cells, and vascular loss in I/R area. DMF treatment suppressed the infiltration of MPO+ neutrophils and the production of proinflammatory cytokines in I/R site after cutaneous I/R injury. in vitro experiments, DMF treatment suppressed the production of reactive oxygen species in pericyte-like cells. These results suggest that DMF treatment might prevent the formation of PUs induced by cutaneous I/R injury via suppressing oxidative stress and subsequent inflammation. DMF treatment during the early phase of decubitus ulcers might protect against further progression.
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Fumarato de Dimetilo/farmacologia , Úlcera por Pressão/etiologia , Úlcera por Pressão/prevenção & controle , Traumatismo por Reperfusão/complicações , Administração Oral , Animais , Fumarato de Dimetilo/administração & dosagem , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Estresse OxidativoRESUMO
INTRODUCTION: Recent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another ß-lactams (VA therapy). METHODS: The present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and ß-lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patients' baseline hospital admittance status, as intensive care unit or general wards. RESULTS: We analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 µg/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02). CONCLUSION: VP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.
Assuntos
Injúria Renal Aguda , Vancomicina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/epidemiologia , Adulto , Antibacterianos/efeitos adversos , Quimioterapia Combinada , Humanos , Japão/epidemiologia , Combinação Piperacilina e Tazobactam/efeitos adversos , Estudos Retrospectivos , Vancomicina/efeitos adversosRESUMO
The physiological response of trees to drought is crucial for understanding the risk of mortality and its feedbacks to climate under the increase in droughts due to climate change, especially for the largest trees in tropical rainforests because of their large contribution to total carbon storage and water use. We determined the response of the mean canopy stomatal conductance per unit leaf area (gs) and whole-tree hydraulic conductance (Gp) of the largest individuals (38-53 m in height) of a typical canopy tree species in a Bornean tropical rainforest, Dryobalanops aromatica C.F.Gaertn., to soil moisture reduction by a 4-month rainfall exclusion experiment (REE) based on the measurements of sap flux and leaf water potentials at midday and dawn. In the mesic condition, the gs at vapor pressure deficit (D) = 1 kPa (gsref) was small compared with the reported values in various biomes. The sensitivity of gs to D (m) at a given gsref (m/gsref) was ≥ 0.6 irrespective of soil moisture conditions, indicating intrinsically sensitive stomatal control with increasing D. The REE caused greater soil drought and decreased the mean leaf water potentials at midday and dawn to the more negative values than the control under the relatively dry conditions due to natural reduction in rainfall. However, the REE did not cause a greater decrease in gs nor any clear alteration in the sensitivity of gs to D compared with the control, and induced greater decreases in Gp during REE than the control. Thus, though the small gs and the sensitive stomatal response to D indicate the water saving characteristics of the studied trees under usual mesic conditions, their limited stomatal regulation in response to soil drought by REE and the resulting decline in Gp might suggest a poor resistance to the unusually severe drought expected in the future.
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Dipterocarpaceae/fisiologia , Secas , Estômatos de Plantas/fisiologia , Transpiração Vegetal , Floresta Úmida , Folhas de Planta/fisiologia , Solo , Árvores , ÁguaRESUMO
PURPOSE: The plasma membrane localization and transport activity of multidrug resistance- associated protein 2 (MRP2/ABCC2) and P-glycoprotein (P-gp/ABCB1) efflux transporters are governed by transporter-associated proteins. Phosphatidylinositol 4,5-bisphosphate (PIP2) formed by phosphatidylinositol 4-phosphate 5-kinase type 1 (PIP5K1) activates the linker function of radixin for efflux transporters. Radixin is involved in the plasma membrane localization of efflux transporters. We examined whether PIP5K1 could be a target for the modulation of transporter activities in hepatocytes and cancer cells. METHODS: The effects of PIP5K1 depletion by siRNA in mouse primary hepatocytes, PANC1 human pancreatic carcinoma cells, and HepG2 human hepatocellular carcinoma cells on the intracellular accumulation of MRP2 and P-gp substrates were examined. RESULTS: PIP5K1A depletion resulted in increased intracellular accumulation of carboxydichlorofluorescein, a MRP2 fluorescent substrate, in mouse primary hepatocytes, PANC1 cells, and HepG2 cells. In PANC1 and HepG2 cells, the transport activities of MRP2 were significantly decreased by PIP5K1C depletion. However, the transport activities of P-gp were unchanged by PIP5K1 depletion. PIP2 levels were unchanged between control and PIP5K1A- or PIP5K1C-depleted HepG2 cells. MRP2 mRNA levels showed few changes in HepG2 cells following PIP5K1A or PIP5K1C depletion. The expression of phosphorylated radixin was decreased by PIP5K1A and PIP5K1C depletion, although total radixin levels were unchanged. CONCLUSIONS: These data suggest that PIP5K1A and PIP5K1C could be target proteins for modulating MRP2 function, partly because of the resulting changes of the linker function of radixin.
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Hepatócitos/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Animais , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Hepatócitos/patologia , Humanos , Camundongos , Camundongos Knockout , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Tumorais CultivadasRESUMO
OBJECTIVE: To evaluate the impact of magnetic resonance imaging/transrectal ultrasound fusion-targeted prostate biopsy on the diagnosis of clinically significant prostate cancer using real-time three-dimensional ultrasound-based organ-tracking technology. METHODS: The present study was a retrospective review of 262 consecutive patients with prostate-specific antigen of 7.1 ng/mL (interquartile range 4.0-19.8). All patients received pre-biopsy magnetic resonance imaging and had a suspicious lesion for clinically significant prostate cancer. All patients underwent a combination of systematic biopsy (6 cores) and three-dimensional ultrasound-based magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (2 cores). The positive rate of any cancer, positive rate of clinically significant prostate cancer, Gleason score and maximum cancer core length were compared between systematic biopsy versus magnetic resonance imaging/transrectal ultrasound fusion-targeted prostate biopsy. RESULTS: Overall, the positive rate of any cancer per patient was 61% (160/262) in systematic biopsy versus 79% (207/262) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001); and that of clinically significant prostate cancer per patient was 46% (120/262) in systematic biopsy versus 70% (181/262) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). The positive rate of any cancer per core was 21.7% (330/1523) in systematic biopsy versus 68.6% (406/592) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001), and that of clinically significant prostate cancer per core was 12.7% (193/1423) in systematic biopsy versus 60.3% (357/592) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). Adding systematic biopsy leads to 13 more cancer cases (5%). The distribution of Gleason score (6/7/8/9/10) was 59/71/23/6/1 in systematic biopsy versus 48/105/36/15/2 in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P = 0.005). The maximum cancer core length was 5 mm (0.5-16) in systematic biopsy versus 8 mm (1-19 mm) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). CONCLUSIONS: Three-dimensional ultrasound-based magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy seems to be associated with a higher detection rate of clinically significant prostate cancer, with fewer cores than systematic random biopsy. However, significant cancer can still be detected by the systematic technique only. A combination of systematic biopsy with the targeted biopsy technique would avoid the underdiagnosis of clinically significant prostate cancer.
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Endossonografia , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico por imagem , Reto , Estudos RetrospectivosRESUMO
A novel C3-symmetric propeller-shaped vanadium(IV/V) oxide cluster complex, [V8O19(4,4'- tBubpy)3] (V8'), has been synthesized from the reaction of the windmill-shaped vanadium(V) oxide cluster complex [V8O20(4,4'- tBubpy)4] (V8) with PPh3 under N2, whereas refluxing V8 in methanol or ethanol under N2 provides tetranuclear oxido(alkoxido)vanadium(IV/V) complexes [V4O6(OR)6(4,4'- tBubpy)2] [R = Me (V4'-Me) and Et (V4'-Et)]. The mixed-valent vanadium(IV/V) clusters V8' and V4' are converted back to V8 under O2. Interconversions of V4' and the oxido(alkoxido)vanadium(V) complexes [V4O8(OMe)4(4,4'- tBubpy)2] (V4) and [V7O17(OEt)(4,4'- tBubpy)3] (V7-Et) are also presented.
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OBJECTIVES: To analyze cases of therapy-related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience. METHODS: A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed. RESULTS: Four testicular tumor patients (4/171, 2.3%) developed therapy-related acute myeloid leukemia and myelodysplastic syndrome. Three of them were affected after complete remission of the primary testicular tumor. A median time interval from a start of chemotherapy to a secondary tumor development was 6.8 years (range 3.7-11.5 years). The median total dose of etoposide, ifosfamide, cisplatin and nedaplatin were 3640 mg/m2 (range 2906-4000 mg/m2 ), 42.7 g (range 19.5-54.0 g), 1100 mg/m2 (range 600-1500 mg/m2 ) and 500 mg/m2 (range 300-1600 mg/m2 ), respectively. Etoposide had the only significant relationship between a cumulative dose and leukemogenesis in univariate analysis (P < 0.05). One patient had complete remission, but the other three patients died. CONCLUSIONS: The present findings show that refractory germ cell tumor patients have an increased risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome. A cumulative dose of etoposide is a significant risk of leukemogenesis. As therapy-related acute myeloid leukemia and myelodysplastic syndrome has a poor prognosis, close follow up is required for refractory germ cell tumor patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/epidemiologia , Síndromes Mielodisplásicas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Segunda Neoplasia Primária/epidemiologia , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Leucemia Mieloide Aguda/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/induzido quimicamente , Neoplasias Embrionárias de Células Germinativas/patologia , Segunda Neoplasia Primária/induzido quimicamente , Estudos Retrospectivos , Neoplasias Testiculares/patologia , Resultado do Tratamento , Adulto JovemRESUMO
The octanuclear oxidovanadium(V) complex [V8O20(4,4'-(t)Bubpy)4] (1; 4,4'-(t)Bubpy = 4,4'-di-tert-butyl-2,2'-bipyridine) was synthesized in multigram-scale quantities by the reaction of VOSO4 with 4,4'-(t)Bubpy in the presence of sodium benzoate under O2. The reaction of 1 with MeOH under air afforded the tetranuclear oxidovanadium(V) complex [V4O8(OMe)4(4,4'-(t)Bubpy)2] (2) selectively. In contrast, treatment of 1 with EtOH or MeOC2H4OH under air gave the heptanuclear oxidovanadium(V) complexes [V7O17(OR)(4,4'-(t)Bubpy)3] (R = Et (3a), MeOC2H4 (3b)) having an unprecedented neutral V7O17(OR) core. Although 3a and 3b are relatively stable in CH2Cl2, slow diffusion of Et2O into the solution of 3a in CH2Cl2 afforded 1 as yellow crystals. Complex 2 was also converted into 1 by recrystallization from CHCl3-CH2Cl2/Et2O. (1)H and (51)V NMR as well as electrospray ionization mass spectrometry studies of the behavior of 2 in CD2Cl2 suggested the formation of the methoxido analogue of 3 (3c, R = Me), which is considered to be an intermediate species in the conversion of 2 to 1. The present results provide a rare example of interconversion among neutral vanadium(V) oxide cluster complexes by changing the solvent systems.
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The vertical structure of a tropical rain forest is complex and multilayered, with strong variation of micro-environment with height up to the canopy. We investigated the relation between morphological traits of leaf surfaces and tree ecological characteristics in a Malaysian tropical rain forest. The shapes and densities of stomata and trichomes on the abaxial leaf surfaces and their relation with leaf characteristics such as leaf area and leaf mass per area (LMA) were studied in 136 tree species in 35 families with different growth forms in the tropical moist forest. Leaf physiological properties were also measured in 50 canopy and emergent species. Most tree species had flat type (40.4 %) or mound type (39.7 %) stomata. In addition, 84 species (61.76 %) in 22 families had trichomes, including those with glandular (17.65 %) and non-glandular trichomes (44.11 %). Most leaf characteristics significantly varied among the growth form types: species in canopy and emergent layers and canopy gap conditions had higher stomatal density, stomatal pore index (SPI), trichome density and LMA than species in understory and subcanopy layers, though the relation of phylogenetically independent contrasts to each characteristic was not statistically significant, except for leaf stomatal density, SPI and LMA. Intrinsic water use efficiency in canopy and emergent tree species with higher trichome densities was greater than in species with lower trichome densities. These results suggest that tree species in tropical rain forests adapt to a spatial difference in their growth forms, which are considerably affected by phylogenetic context, by having different stomatal and trichome shapes and/or densities.