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The objective of the present study was to evaluate the risk factors and outcomes associated with hyponatremia in patients with Guillain-Barré syndrome (GBS). We retrospectively studied 80 consecutive patients with GBS who visited our hospital and compared clinical, laboratory, and electrophysiological findings of patients with and without hyponatremia. Disability was evaluated using the Hughes grading system. Of the 80 patients, 18 (23%) had hyponatremia. Hyponatremia was significantly associated with older age (P = 0.003), urinary retention (P < 0.0001), Hughes grade ≥ 4 at admission and nadir (P = 0.003 and P < 0.001, respectively), acute inflammatory demyelinating polyneuropathy subtype (P = 0.017), sepsis (P = 0.001), mechanical ventilator support (P = 0.013), longer hospitalization length of stay (P < 0.0001), and inability to walk independently at 6 months (P < 0.001). Multivariate analysis performed to assess the risk factors of hyponatremia revealed that urinary retention (odds ratio [OR] 30.7, 95% confidence interval [CI] 3.6-264.4; P = 0.002) and mechanical ventilator support (OR 13.8, 95% CI 1.6-118.0; P = 0.017) were significant independent risk factors of hyponatremia. In assessing the outcomes of patients with hyponatremia, multivariate analysis showed that hyponatremia was independently associated with hospitalization length of stay ≥ 60 days and inability to walk independently at 6 month, with the former showing statistical significance but the latter not (OR 9.3, 95% CI 1.8-47.7; P = 0.007 and OR 4.9, 95% CI 0.9-26.3; P = 0.066, respectively). Therefore, we demonstrate that, along with mechanical ventilator support, urinary retention-possibly indicating autonomic dysfunction-is a risk factor of hyponatremia in GBS. Moreover, we confirm that hyponatremia is associated with poor outcome in GBS.
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Síndrome de Guillain-Barré , Hiponatremia , Humanos , Hiponatremia/etiología , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/terapia , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Tiempo de Internación , Respiración ArtificialRESUMEN
OBJECTIVES: To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort). METHODS: Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test. RESULTS: The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027). CONCLUSIONS: MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.
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BACKGROUND: In liver transplant patients with hypoplastic portal vein (PV), when the narrowed segment is extended too deep into the dorsal side of the pancreas, it is difficult and dangerous to reconstruct the interposition graft from the upper part of the pancreas. Herein, we present a case of PV reconstruction with the autologous mesosystemic shunt vessel from the caudal side of the pancreas in a situation where the narrowed PV was deep, and we discuss the technical details. CASE PRESENTATION: A 25-year-old woman presented with cholestatic liver cirrhosis due to biliary atresia after Kasai procedure. Since her jaundice progressed, she was referred to our hospital for liver transplantation. Laboratory tests showed that her total bilirubin was elevated to 7.6 mg/dL. The Model for End-Stage Liver Disease score was 18, and the Child-Pugh score was 9 (Grade B). She underwent living donor liver transplantation (LDLT) using a right hemi-liver graft procured from her 54-year-old mother. The conventional approach from the cephalad side to the superior mesenteric vein (SMV) and splenic vein (SpV) confluence behind the pancreas was extremely difficult in this case because the confluence of SMV and SpV was close to the lower edge of the pancreas. Therefore, we decided to perform PV reconstruction from the caudal side. The main trunk of PV was documented as narrow (5 mm in diameter), for which retro-pancreatic pull-through PV reconstruction was successfully performed using her own mesosystemic shunt vessel. A contrast computed tomography (CT) scan was performed on postoperative day 5 because of an elevation of D-dimer and found a partial thrombus in the left pulmonary artery, as well as in the PV and left renal vein. Thereafter, thrombolytic therapy with low-molecular-weight heparin was started immediately and switched to a direct oral anticoagulant. The follow-up CT taken 3 months after liver transplantation revealed a patent PV without thrombus; therefore, anticoagulant therapy was discontinued. Currently, the patient has been well and active with a patent PV without anticoagulant therapy for 3 years after LDLT. CONCLUSIONS: Retro-pancreatic pull-through reconstruction of the hypoplastic PV is a feasible and effective method when conventional reconstruction is not indicated.
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Heterocapsa circularisquama RNA virus (HcRNAV) is the only dinoflagellate-infecting RNA virus cultured. However, only two strains of HcRNAV have been registered with complete genome sequences (strains 34 and 109 for UA and CY types, respectively). To extend the genomic information of HcRNAV, we performed full-genome sequencing of an unsequenced strain of HcRNAV (strain A8) using the fragmented and primer-ligated double-stranded RNA (dsRNA) sequencing (FLDS) method. The complete genome of HcRNAV A8 with 4457 nucleotides (nt) was successfully determined, and sequence alignment of the major capsid protein gene suggested that A8 was a UA-type strain, consistent with its intraspecific host specificity. The complete sequence was found to be 80 nt longer at the 5' terminus than the registered sequences of HcRNAV strains (34 and 109), suggesting that FLDS is more reliable for determining the terminal sequence than conventional methods (5' Rapid Amplification of cDNA End). Our study contributes to a better understanding of dinoflagellate-infecting viruses with limited sequence data.
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Dinoflagelados , Virus ARN , Virus , ARN Bicatenario/genética , Virus/genética , Virus ARN/genética , Dinoflagelados/genética , Alineación de Secuencia , ARN Viral/genéticaRESUMEN
BACKGROUND: Children requiring liver transplantation generally have severe growth retardation. Recipients experience posttransplantation catch-up growth, although some show short adult heights. We aimed to determine decades-long catch-up growth trends and risk factors for short adult height following liver transplantation. METHODS: We analyzed long-term height Z scores and risk factors for short adult height in a single-center retrospective cohort of 117 pediatric liver transplantation recipients who survived >5 y, with 75 of them reaching adult height. RESULTS: Median age at transplantation was 1.3 y, and the most common primary diagnosis was biliary atresia (76.9%). Mean height Z scores pretransplantation and 1, 3, and 8 y after transplantation were -2.26, -1.59, -0.91, and -0.59, respectively. The data then plateaued until 20 y posttransplantation when mean adult height Z score became -0.88, with a median follow-up of 18.6 y. Nineteen recipients did not show any catch-up growth, and one quarter of recipients had short adult height (<5th percentile of the healthy population). Multivariate analysis identified old age (odds ratio, 1.22 by 1 y; P = 0.002), low height Z scores at transplantation (odds ratio, 0.46 by 1 point; P < 0.001), and posttransplantation hospital stay ≥60 d (odds ratio, 4.95; P = 0.015) as risk factors for short adult height. In contrast, prolonged steroid use after transplantation was not considered a significant risk factor. CONCLUSIONS: Although tremendous posttransplantation catch-up growth was observed, final adult height remained inadequate. For healthy physical growth, liver transplantation should be performed as early as possible, before growth retardation becomes severe.
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Trasplante de Hígado , Niño , Humanos , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Estudios de Seguimiento , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Factores de Riesgo , EstaturaRESUMEN
BACKGROUND: Progress testing is an assessment method in which an examination reflecting competencies at graduation is regularly administered to students over multiple years, thereby facilitating self-directed learning. However, the significance of the objective structured clinical examination as a progress test in undergraduate education, needs to be determined. This study provides evidence of the role of the objective structured clinical examination for progress testing and optimal scoring methods for assessing students in different academic years. METHODS: We conducted a sequential explanatory mixed-methods pilot study. Participants were assessed using the Item Rating Scale, the year-adjusted Global Rating Scale, and the Training Level Rating Scale. The characteristics of each scale were compared quantitatively. In addition, the influence of the objective structured clinical examination as a progress test on learning attitudes was examined. Qualitative data from a post-examination questionnaire were analyzed, using content analysis to explore influences on self-directed learning. RESULTS: Sixth and fifth year clinical students (n = 235) took the objective structured clinical examination progress test. The total Item Rating Scales were recorded (%) as 59.03 ± 5.27 and 52.64 ± 5.08 (p < 0.01); Training Level Rating Scale was 3.94 ± 0.39 vs 3.22 ± 0.42 (p < 0.01); and the year-adjusted Global Rating Scale was 4.25 ± 0.44 vs 4.32 ± 0.52 (no significant difference), for the sixth and fifth year students, respectively. The correlations across stations and the reliability of each station were satisfactory. Four categories were identified in the qualitative analysis: "motivation to learn during the clinical clerkship was promoted," "dissatisfied with being asked about things they had not experienced," "confusion about being unable to use conventional test-taking strategies," and "insufficient understanding of competencies at graduation." The scores indicated significant differences in performance according to training year. CONCLUSIONS: This study provides evidence that the objective structured clinical examination can be used as a progress testing tool for undergraduate clinical clerkships. Further enhancement of training opportunities and dissemination of performance competency goals in clerkship curricula are required if we intend to promote self-directed learning through progress testing.
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Prácticas Clínicas , Educación de Pregrado en Medicina , Estudiantes de Medicina , Humanos , Proyectos Piloto , Reproducibilidad de los Resultados , Aprendizaje , Competencia ClínicaRESUMEN
Introduction: The mRNA-based vaccine was released as a COVID-19 prophylactic; however, its efficacy in organ transplant recipients is unknown. This study aimed to clarify this in liver transplant recipients. Methods: Herein, liver transplant recipients from two hospitals who received vaccines were included. Immunoglobulin-G antibodies against the spike and nucleocapsid proteins were measured chronologically after the second, third, and fourth vaccine doses. Results: Antibody levels in 125 liver transplant recipients and 20 healthy volunteers were analyzed. The median age at transplant was 35 (interquartile range 1, 53) years, and the period between transplant and the first dose was 15.2 ± 7.7 years. After the second and third doses, 89.1% and 100% of recipients displayed a positive humoral response, respectively. Anti-spike antibodies after the second dose were significantly reduced at 3 and 6 months, compared to that at 1 month (26.0 [5.4, 59.5], 14.7 [6.5, 31.4] vs. 59.7 [18.3, 164.0] AU/mL, respectively, p < 0.0001). However, a booster vaccine significantly elevated anti-spike antibodies in LT recipients (p < 0.0001) as well as in healthy controls (p < 0.0001). Additionally, the decay rate was comparable between the transplant recipients and controls (2.1 [0.8, 4.5] vs. 2.7 [1.1, 4.1] AU/mL/day, p = 0.9359). Only 4.0% of vaccinated transplant recipients were positive for anti-nucleocapsid antibodies. Conclusion: Liver transplant recipients can acquire immunity similar to that of healthy people through vaccination against SARS-CoV-2. The antibody decay rate is the same, and booster vaccinations should be administered similarly to that in healthy individuals.
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Sulfur-33(33 S) stable-isotope labeled taurine, 2-aminoethanesulfonic acid, has been synthesized, and a series of solution and solid-state 33 S nuclear magnetic resonance (NMR) experiments at 14.1 and 18.8 T, respectively, have been carried out at room temperature. The single peak of a solution 33 S NMR spectrum in 0.1-mM [33 S]-taurine in D2 O can be observed with the signal-to-noise (S/N) ratio of 9 in 40,000 scans, which paves the way toward in vivo analysis of pharmacokinetics and metabolism of 33 S-labeled taurine. Undistorted magic-angle-spinning (MAS) and static 33 S NMR spectra of polycrystalline [33 S]-taurine are observed with sufficient S/N ratios for analysis, and the magnitudes of 33 S EFG and CS tensors can be obtained.
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BACKGROUND: The incidence of de novo malignancy (DNM) after liver transplantation (LT) is reported to be 3.1% to 14.4%. It is a known cause of death in long-term recipients. This study aimed to clarify the clinical features and risk factors of DNM. METHODS: Recipients who underwent adult-to-adult living-donor LT (LDLT) and survived for >6 months were investigated. The medical records were retrospectively reviewed. This study was approved by the institutional review board. RESULTS: In total, 180 patients were included. The indications for LDLT were hepatocellular disease (n = 62), metabolic liver disease (n = 50), cholestatic disease (n = 46), acute liver failure (n = 12), and others (n = 10). The median age at LDLT was 48 (18-71) years, and the follow-up period was 15 (0-29) years. De novo malignancy was diagnosed in 24 recipients (28 sites), including the digestive tract (n = 9), genitourinary (n = 5), gynecologic (n = 5), lung (n = 4), hematological (n = 3), and others (n = 2). The median duration from LDLT to DNM was 7 (0-19) years. Four patients were lost to follow-up due to advanced-stage cancer. R0 (curative treatment) for non-hematological DNM was achieved in 19 lesions (95%). The 10- and 20-year DNM incidence rates were 11% and 20%, respectively. The 20-year survival rates of DNM (59.6%) and non-DNM (59.9%) patients were not significantly different. De novo malignancy was significantly higher in patients with primary sclerosing cholangitis than in others (P < .05). CONCLUSIONS: Even in DNM recipients, early detection of malignancy and R0 treatment promises long-term outcomes comparable to those of non-DNM recipients.
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Trasplante de Hígado , Neoplasias , Humanos , Adulto , Femenino , Trasplante de Hígado/efectos adversos , Donadores Vivos , Estudios Retrospectivos , Neoplasias/epidemiología , Neoplasias/etiología , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Various formulae have been used for the estimation of standard liver volume (SLV) in preparation for living donor liver transplantation (LDLT). However, these formulae have the disadvantage of being constructed using parameters that are substantially affected by the patient's condition. Here, we aimed to establish more precise formulae that are less affected by the general condition of the patient. METHODS: We analyzed the liver volumes of LDLT donors and patients with normal livers (total: n = 213) using the SYNAPSE VINCENT imaging analysis system, to develop new formulae. The accuracy of the new formulae were compared with those of existing formulae in a separate validation group of healthy patients (n = 200). The new formulae were also validated using 81 LDLT recipients to assess their utility for graft selection in LDLT. RESULTS: Body surface area (BSA) and skeletal muscle mass index (SMI) independently affected total liver volume (TLV). We produced new formulae for SLV incorporating SMI: SLV = 32.2 × L3-SMI-466.9 for men, with R2 .92, and 25.7 × L3-SMI-55.97 for women, with R2 .79 (alongside a BSA formula with R2 .57), which provided the most accurate predictions of TLV in the validation group. A graft volume (GV)/SLV <.35, calculated using the new formulae, predicted the postoperative prognosis, including the development of small-for-size syndrome, sepsis, or acute rejection, significantly more effectively than GV/SLV using the previous formulae. CONCLUSIONS: The newly developed L3-SMI-based formula is more accurate for the estimation of SLV than previously reported formulae, and may thus help to improve the safety of LDLT.
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Trasplante de Hígado , Masculino , Humanos , Femenino , Trasplante de Hígado/métodos , Donadores Vivos , Tamaño de los Órganos , Hígado/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
The sulfur electric-field-gradient tensor for a disulfide bond in 33 S2 -labeled L-cystine has been investigated by 33 S nuclear quadrupole resonance (NQR). 33 S2 -labeled L-cystine is synthesized by introduction of disulfide ions prepared from elemental 33 S-sulfur into an amino acid derivative, the side chain of which is iodinated. In its NQR spectrum, sharp single peaks are observed at between 24.63 and 24.90 MHz in the temperature range from 80 to 298 K. The two-dimensional nutation echo 33 S NQR experiment is carried out at 160 K, and the quadrupole coupling constant, CQ , and the asymmetric parameter, ηQ , are obtained to be 46.9(9) MHz and 0.6(1), respectively. The calculated 33 S electric-field-gradient tensor components with respect to the molecular frame is briefly discussed.
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BACKGROUND: Although chronic kidney disease (CKD) after liver transplantation (LTx) is a common complication in adults, its long-term significance after pediatric LTx remains unclear. We examined the decades-long transition of renal function and revealed the risk factors for late-onset CKD after pediatric LTx in a single-center retrospective cohort of 117 pediatric LTx recipients who survived >5 y. METHODS: The estimated glomerular filtration rate (eGFR) and CKD stages were calculated using serum creatinine. Risk factor analysis for late-onset CKD was performed in 41 patients whose eGFR could be evaluated at >20 y after LTx. RESULTS: The median age at LTx was 1.3 y, and most primary diagnoses were biliary atresia (77%). The mean pre-LTx and 1, 5, 10, 20, and >20 y post-LTx eGFRs were 180, 135, 131, 121, 106, and 95 mL/min/1.73 m 2 , respectively, with a median renal follow-up period of 15 y. The eGFR declined by 47% at >20 y after LTx ( P < 0.001). CKD was observed in 8%, 19%, and 39% of cases at 10, 20, and >20 y after LTx, respectively. In patients receiving cyclosporine, trough levels were 1.5 times higher in those with CKD up to 10 y after LTx. The multivariate analysis showed that older age at LTx (odds ratio, 1.3 by 1 y; P = 0.008) and episodes of repeated/refractory rejection (odds ratio, 16.2; P = 0.002) were independent risk factors of CKD >20 y after LTx. CONCLUSIONS: In conclusion, renal function deteriorates slowly yet steadily after pediatric LTx. Long-term careful surveillance is essential after pediatric LTx, especially in repeated/refractory rejection or long-term high trough-level use of cyclosporine cases.
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Trasplante de Hígado , Insuficiencia Renal Crónica , Adulto , Humanos , Niño , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Riñón , Ciclosporina , Tasa de Filtración GlomerularRESUMEN
This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and severity assessment. Patients with MPA (n = 37) and other non-inflammatory neurological diseases (ONDs; n = 12) were enrolled, and the peripheral nerves of all patients were evaluated using nerve conduction studies. We compared the clinical characteristics and 14 serum biomarker profiles among patients with MPA and PN, MPA without PN, and ONDs. Patients with MPA had a higher prevalence of motor neuropathy than patients with ONDs. Among the patients with MPA, those with motor neuropathy had significantly higher total Birmingham Vasculitis Activity Scores and serum levels of C-reactive protein (CRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 than patients without motor neuropathy. Multivariable analyses adjusted for age, serum CRP level, and diabetes mellitus showed that high serum levels of TIMP-1 were independently related to a diagnosis of motor neuropathy in MPA. Additionally, there were significant negative correlations between the serum levels of TIMP-1 and compound muscle action potential amplitudes. Serum levels of TIMP-1 may be associated with the pathomechanism of motor neuropathy in MPA and could be a useful biomarker for diagnosing and evaluating the severity of motor neuropathy in MPA.
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Poliangitis Microscópica , Enfermedades del Sistema Nervioso Periférico , Humanos , Inhibidor Tisular de Metaloproteinasa-1 , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Biomarcadores , Proteína C-ReactivaRESUMEN
BACKGROUND: Fungal infection may develop because of immunosuppression after organ transplantation, in which invasive types, such as Aspergillus and Mucorales, fungi cause morbidity. We present a case of disseminated mucormycosis due to Cunninghamella bertholletiae after ABO-incompatible living donor liver transplantation (LDLT). CASE PRESENTATION: A 47-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma underwent an ABO-incompatible LDLT using a graft procured from his son, who had a different blood type. Rituximab and mycophenolate mofetil were administered 3 weeks before LDLT as immunosuppressive therapy. Although liver graft function improved, mass-like infiltrates appeared in the lungs following intubation for > 1 week due to impaired consciousness. The brain magnetic resonance imaging findings were normal. Decreased ejection fraction and ST elevation were detected on echocardiography and electrocardiography, respectively. There was no dominant stenosis on coronary arteriography. The recipient underwent segmentectomy of the right lung 20 days after LDLT. C. bertholletiae was identified from a specimen using polymerase chain reaction, thus establishing a diagnosis of mucormycosis. Multiple infarctions in the brain, heart, and kidney developed within 2 weeks. Treatment with amphotericin B was ineffective. The patient developed circulatory collapse, and a temporary pacemaker and percutaneous coronary intervention were required for cardiac infarction. The recipient died of cardiac failure 27 days after the LDLT. Autopsy revealed disseminated mucormycosis involving the brain, thyroid, heart, lung, liver, gastrointestinal tract, and both kidneys. In addition, fungal endocarditis may have been responsible for septic emboli in multiple organs, resulting in multiple organ invasion. Hypothrombocytopenia was present since the pre-transplant period, and the recipient was diagnosed posthumously with myelodysplastic syndrome due to hereditary abnormalities. Multiple factors such as organ transplantation, bone marrow dysfunction, immunosuppression, and inadequate administration of antifungal reagents might have promoted mucormycosis development in our patient. CONCLUSIONS: Mucormycosis by C. bertholletiae is a fatal complication; thus, early diagnosis and treatment are warranted before multiple organ invasion.
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Heterocapsa circularisquama RNA virus (HcRNAV) is the only dinoflagellate-infecting RNA virus that has been isolated to date. We herein investigated the diversity of the major capsid protein gene of HcRNAV and related viruses using degenerate PCR and in silico ana-lyses. Diverse sequences related to HcRNAV were successfully amplified from marine sediments. Amplicons contained conserved and variable regions; the latter were predicted to be located on the outer surface of the capsid. Our approach provides insights into the diversity of viruses that are difficult to isolate in the environment and will enhance rapidly growing metagenome sequence repositories.
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Virus ARN , Virus , Cápside , Proteínas de la Cápside/genética , Reacción en Cadena de la Polimerasa , Virus ARN/genética , Virus/genéticaRESUMEN
We encountered a 47-year-old woman with polycystic liver disease (PLD) and severe malnutrition successfully treated by living-donor liver transplantation (LDLT). Her PLD became symptomatic with abdominal distension and appetite loss. Transcatheter arterial embolization and percutaneous cyst drainage failed to improve her symptoms. ABO-incompatible LDLT from her husband was performed after rituximab administration and mycophenolate mofetil introduction. Although she showed severe postoperative complications, she ultimately regained the ability to walk and was discharged. Because advanced PLD cases are difficult to treat conservatively or with surgery, like fenestration and hepatectomy, liver transplantation should be considered before it becomes too late.
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Trasplante de Hígado , Sistema del Grupo Sanguíneo ABO , Adulto , Incompatibilidad de Grupos Sanguíneos/complicaciones , Femenino , Humanos , Hígado , Donadores Vivos , Persona de Mediana EdadRESUMEN
Serum cytokine levels were comprehensively measured, and the association with cerebrovascular lesions on brain magnetic resonance imaging (MRI) in microscopic polyangiitis (MPA) patients was investigated. The initial serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were significantly higher in the high-grade white matter hyperintensities (WMH) group than those in the low-grade WMH group. In multivariate analyses, high serum levels of GM-CSF were independently associated with high-grade WMH. The initial serum GM-CSF levels correlated positively with the Birmingham Vasculitis Activity Score and semi-quantitative scales of WMH. The initial serum GM-CSF levels were associated with the severity of WMH in MPA patients.
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Enfermedades de los Pequeños Vasos Cerebrales/sangre , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Poliangitis Microscópica/sangre , Poliangitis Microscópica/diagnóstico por imagen , Gravedad del Paciente , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Cherimolacylopeptide E (1) is a cyclic hexapeptide isolated from the seeds of Annona cherimola. Peptide 1 reportedly exhibits potent cytotoxicity against KB cells (IC50 0.017 µM). To confirm the structure and bioactivity of 1, we conducted a total synthesis of its proposed structure. The synthesis was accomplished via solid-phase peptide elongation and macrocyclization by employing Fmoc/OAll-protected amino acids on 2-Cl-trityl resin. NMR analysis revealed that synthetic 1 exists in two conformations in pyridine-d5 . As the spectroscopic data of the major conformer of synthetic 1 were consistent with those of natural 1, the structure of cherimolacyclopeptide E was confirmed to be 1. However, our synthetic 1 exhibited low cytotoxicity against KB cells (IC50 > 100 µM). In contrast to previously-reported findings, our synthetic 1 exhibited little antibacterial activity against Escherichia coli.
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Annona/química , Péptidos Cíclicos/farmacología , Técnicas de Síntesis en Fase Sólida , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Células KB , Conformación Molecular , Péptidos Cíclicos/síntesis química , Péptidos Cíclicos/químicaRESUMEN
Naturally occurring peptides form unique 3D structures, which are critical for their bioactivities. To gain useful insights into drug design, the relationship between the 3D structure and bioactivity of the peptides has been studied. Solid-state nuclear magnetic resonance (NMR) analysis of the 42-residue amyloid ß-protein (Aß42) suggested the presence of toxic conformers with a turn structure at positions 22 and 23 in the aggregates. Antibodies specific to this turn structure could be utilized for immunotherapy and early diagnosis of Alzheimer's disease. Solution NMR analysis of apratoxin A, a cyclic depsipeptide with potent cytotoxicity, proposed an accurate structural model with an important bend structure, which led to the development of highly active mimetics. X-ray crystal analysis of PF1171F, a cyclic hexapeptide with insecticidal activity, indicated the formation of 4 intramolecular hydrogen bonds, which play an important role in cell membrane permeability of PF1171F.
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Productos Biológicos/química , Productos Biológicos/farmacología , Diseño de Fármacos , Péptidos/química , Péptidos/farmacología , Animales , Humanos , Conformación ProteicaRESUMEN
A bivalve-killing marine dinoflagellate, Heterocapsa circularisquama, is susceptible to the infectious single-stranded RNA virus, Heterocapsa circularisquama RNA virus (HcRNAV). The ecological relationship between H. circularisquama and HcRNAV was intensively studied from 2001 through 2005; however, only limited data are available for the ecological dynamics of HcRNAV before 2001. In this study, we applied radiometric dating and reverse transcription PCR (RT-PCR) to determine the chronological distribution of HcRNAV in a marine sediment core sampled from the Uranouchi Inlet, Kochi, Japan, where H. circularisquama was first discovered. Our results show that HcRNAV had existed in the inlet long before its first bloom in 1988. Furthermore, five HcRNAV variants, phylogenetically distinguishable based on the nucleotide sequence of the major capsid protein (MCP) gene, were identified. These variants were found to be distributed throughout the core over time, suggesting that the HcRNAV sequences registered in the NCBI database are only a portion of the variants that have emerged in the history of HcRNAV diversification. Herein, we have verified the applicability of the retrospective approach for speculating the distribution of algal RNA viruses over time in aquatic environments.