RESUMO
Endodermal cyst (EC) is a benign tumor that can arise along the craniospinal axis. Infrequently, ECs undergo malignant transformation. A 43-year-old man presented with numbness in the right arm, leg and occipitalgia. MRI revealed a multicystic, intradural extramedullary tumor at C2 with enhancement along the ventral surface of the spinal cord. Blood test showed an abnormal increase in serum carbohydrate antigen 19-9 (CA 19-9) level. Systemic positron emission tomography-computed tomography was normal. He underwent total tumor resection and was diagnosed with EC. He developed double vision, hearing loss, and swallowing difficulty on postoperative day 70. Cerebral MRI revealed marked extensions of leptomeningeal dissemination. The serum CA 19-9 level increased continuously and finally reached 1515.0 U/ml. He died of respiratory failure on day 108. An autopsy did not reveal abnormalities in the abdominal and chest organs. On microscopic examination, the post-mortem specimen revealed adenocarcinoma. Immunohistochemically, both the surgical and autopsy specimens were positive for CA 19-9. Spinal ECs may lead to malignant transformation with leptomeningeal dissemination that causes abnormal elevation of serum CA 19-9 levels.
Assuntos
Cistos do Sistema Nervoso Central , Cistos , Masculino , Humanos , Adulto , Cistos do Sistema Nervoso Central/cirurgia , Medula Espinal/patologia , Imageamento por Ressonância Magnética , Diagnóstico DiferencialRESUMO
Histiocytes and dendritic cells may display cytological atypia and an aberrant immunophenotype even in reactive processes. Herein, we describe two cases of "Hodgkinoid histiocytosis" that show distinctive clinicopathological features, mimicking morphologically classic Hodgkin lymphoma (CHL), but suggesting reactive histiocytic/dendritic cell proliferation in lymph nodes. Both the patients presented with peripheral lymphadenopathy and blood eosinophilia with skin manifestations. Lymph node biopsy revealed scattered large histiocytes resembling Hodgkin cells with a round or stellate shape, abundant cytoplasm, and distinct nucleoli admixed in a predominant inflammatory background. The Hodgkinoid histiocytes occasionally showed emperipolesis. They expressed CD30, S100, and PD-L1 proteins but lacked PAX5 and CD1a expressions, Epstein-Barr association, BRAF V600E mutation, and PD-L1 gene amplification. Neither of the patients showed overt progression to malignant haematopoietic neoplasms during the disease course. An identical case series of four patients has been reported to date. Both these series highlight the potential of being interpreted as CHL due to the presence of Hodgkinoid histiocytes with CD30 positivity.
Assuntos
Eosinofilia , Histiocitose , Doença de Hodgkin , Antígeno B7-H1 , Eosinofilia/complicações , Eosinofilia/patologia , Histiócitos/patologia , Histiocitose/complicações , Histiocitose/patologia , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Humanos , Antígeno Ki-1 , Proteínas S100RESUMO
OBJECTIVE: We investigate the current status of screening for essential thrombocythemia(ET)and polycythemia vera(PV), at our hospital. METHODS: According to the World Health Organization(WHO)diagnostic criteria. PATIENTS: All patients who visited Juntendo University Urayasu Hospital between May 1984(when the hospital opened)and January 2019. RESULT: More than 90% of patients with elevated platelet counts(PLT)(n=25,062)and more than 90% of patients with elevated hemoglobin( Hb)or hematocrit(Ht)levels(n=16,422)did not visit the department of hematology, suggesting that there could be a high percentage of patients with potentially latent ET and PV visiting the hospital. In addition, a large number of patients fulfilling the laboratory criteria for ET/PV visited various departments of the hospital other than the department of hematology. CONCLUSION: Because ET/PV manifests with diverse symptoms, including non-specific symptoms and symptoms pertaining to other organ systems. Based on the findings, we consider that it is essential to disseminate information about the WHO diagnostic criteria/clinical symptoms and possibility of latent ET/PV to all departments of the hospital, and to establish cooperation between the department of hematology and other departments.
Assuntos
Policitemia Vera , Trombocitemia Essencial , Humanos , Policitemia Vera/diagnóstico , Policitemia Vera/epidemiologia , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/epidemiologiaRESUMO
A 42âyearâold woman. At week 27 of pregnancy, she developed subcortical hemorrhage and underwent open cranial surgery for hematoma evacuation. The platelet(Plt)count was 297,000/µL. At week 34 of pregnancy, she developed subcortical hemorrhage again. The Plt count was 429,000/µL. At week 35 of pregnancy, the ventricular rupture and she underwent drainage and emergency cesarean section. The Plt count was 687,000/µL. Two days after delivery, hemorrhage was detected. The Plt count was 815,000/µL. Six days after delivery, she developed infarction. The Plt count was 915,000/µL. MRI revealed no evidence of aneurysm, arteriovenous malformations or tumor. Ten days after delivery, the Plt count was 1,173,000/µL. Bone marrow examination led to the diagnosis of essential thrombocythemia(ET). JAK2, CARL and MPL was negative. She was rated as"lowârisk"by IPSETâthrombosis, and as"ultralow"risk by revised IPSETâthrombosis. von Willebrand factor(VWF)activity was as high as 247%. The bleeding time and platelet aggregation activity were normal. There was no evidence of disseminated intravascular coagulation(DIC)or hypertensive disorders of pregnancy(HDP). She died of cerebral hemorrhage and infarction, 26 days after delivery.
Assuntos
Trombocitemia Essencial , Adulto , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Cesárea , Feminino , Humanos , Período Pós-Parto , Gravidez , Trombocitemia Essencial/complicaçõesRESUMO
In Japan, ibrutinib has been approved as both a front-line and later-line treatment for chronic leukemia/small lymphocytic lymphoma(CLL/SLL). However, little is known about the actual outcomes and adverse events(AEs)associated with the use of ibrutinib in Japanese patients. OBJECTIVE: The outcomes and AEs of patients treated with ibrutinib in a real-world setting were investigated. METHODS: A retrospective cohort study of all patients with CLL/SLL who were treated with ibrutinib at a single institution was conducted. RESULT: In total, 10 patients, including 5 treatment-naïve patients(50%), were enrolled. The median follow-up period was 9.8 months(range, 0.2-21.6 months), and the estimated overall response rate (ORR: complete remission plus partial remission)was 60%. The median overall survival and progression-free survival outcomes were not reached. During the follow-up period, 4 patients(40%)had at least one AE and 1 patient(10%)had at least one grade≥3 AE. Ibrutinib was discontinued in 4 patients(40%)because of AEs in 2 patients(20%), the progression of CLL in 1 patient(10%), and financial reasons in 1 patient(10%). Richter's transformation did not occur in any of the cases. CONCLUSION: The ORR was lower(60%)than that observed in clinical trials. The frequency and severity of AEs were both relatively low, although the discontinuation rate was high(40%). Patient education and medication adherence were considered important.
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Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Humanos , Japão , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas , Pirazóis/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 63-year-old woman was referred to our department in 2015 because of anemia and thrombocytosis. MPL W515/K was positive, JAK-2V617F and CALR exon 9 were negative. Bone marrow(BM)biopsy led to a diagnosis of primary myelofibrosis (PMF)in the prefibrotic/early stage(Grade 1). BMbiopsy performed in 2016 showed overt fibrotic stage(Grade 2). She was classified according to the Dynamic International Prognostic Scoring System(DIPSS)as intermediate(Int)-â ¡risk. Ruxolitinib 10 mg daily was initiated. Ruxolitinib was suspended for hepatic dysfunction after the dose was increased to 15 mg. Subsequently, ruxolitinib was resumed at 10 mg. BM biopsy performed in 2017 showed progression of myelofibrosis(MF)to Grade 3. BM biopsy performed in 2018 showed improved to Grade 0-1, however, BM was fatty. Currently in 2019, she continues to be on ruxolitinib. Results of immunohistochemical staining of BM biopsy specimens for cytokines and CD34 suggested the role of cytokines in the pathogenesis of the PMF. It was speculated that ruxolitinib blocked the production of cytokines to ameliorate the MF and restore the hematopoietic function of the BM. Although the pathogenesis of the fatty marrow remained unclear, the possibility of involvement of ruxolitinib cannot be denied.
Assuntos
Mielofibrose Primária , Medula Óssea , Feminino , Fibrose , Humanos , Pessoa de Meia-Idade , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Pirazóis , PirimidinasRESUMO
BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis of unknown cause involving the brain and accompanied by prominent eosinophilia. Intracardiac thrombosis is a major cardiac complication of EGPA that may cause thromboembolism. CASE PRESENTATION: A 53-year-old man presenting with abulia (consciousness disturbance) and left upper limb paralysis was admitted to our hospital. His case was complicated by penetrating branches, small vessel infarcts, and endocardial thrombosis in the right and left ventricle. Cardiomyopathy was also observed. Sixteen days after admission, the patient died from intracranial hemorrhage. Brain autopsy revealed two major findings: 1) large hemorrhagic infarction caused by cardiac embolism; and 2) granuloma and eosinophil infiltration. Vasculitis was accompanied by eosinophil infiltration in the cortical blood vessels and granuloma. CONCLUSIONS: In this case study, we report autopsy findings of brain infarction in a patient with EGPA and endocardial thrombosis. The brain infarction was caused by the cardiac embolisms and vasculitis.
Assuntos
Infarto Cerebral/etiologia , Síndrome de Churg-Strauss/complicações , Granulomatose com Poliangiite/complicações , Tromboembolia/etiologia , Autopsia , Síndrome de Churg-Strauss/diagnóstico , Granulomatose com Poliangiite/diagnóstico , Cardiopatias/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Renal medullary carcinoma (RMC) is a rare and aggressive cancer associated with the sickle cell trait. The diagnosis of RMC depends on recognition of its histologic features and immunohistochemical deficiency of INI1, but correct diagnosis is sometimes difficult, especially if a patient's information on race, past, and family medical history is unclear. At present, this is the first report on RMC in Japan.
Assuntos
Carcinoma Medular/diagnóstico por imagem , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Traço Falciforme/diagnóstico por imagem , Adulto , Carcinoma Medular/genética , Carcinoma Medular/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Japão , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Proteína SMARCB1/metabolismo , Traço Falciforme/patologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: The clinical features(CF), laboratory data, disease transformation pattern and drug metabolism in essential thrombocythemia(ET)differ between Japan and Western countries. The CF of ET in clinical practice(CP)are more diverse than in prospective clinical studies. We should conduct retrospective analyses in CP. The present study was aimed at evaluating the efficacy, safety and tolerability of anagrelide(ANA)monotherapy and combined ANA plus hydroxycarbamide(HC)in Japanese ET. PATIENTS AND METHODS: We have a total of 35 cases. Sixteen patients received ANA monotherapy, 10 received ANA plus HC, and 9 received ANA plus other drugs. RESULTS: Comparison among three groups revealed the absence of differences in response rate(platelet count C60×10 / / 4/mL, platelet count C40×104/mL)(43.8%, 6.3% vs. 50.0%, 10.0% vs. 44.4%, 11.1%), treatment continuation rate(81.3% vs. 40.0% vs. 55.6%), median daily dose of ANA(1.00 mg in all three groups)or median treatment period(days)(259 vs. 198.5 vs. 161.0), the treatment continuation rate tended to be lower in the combined ANA plus HC. The incidence of all adverse events(AEs)was higher in the ANA monotherapy(45.7%)than ANA plus HC(28.6%)or ANA plus other drugs(25.7%), the AEs were mild in all groups. CONCLUSION: The tolerability of ANA monotherapy, ANA plus HC, and ANA plus other drugs were good.
Assuntos
Hidroxiureia/uso terapêutico , Quinazolinas/efeitos adversos , Trombocitemia Essencial , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Japão , Estudos Retrospectivos , Trombocitemia Essencial/tratamento farmacológicoRESUMO
A 59-year-old female was diagnosed as pulmonary aspergillosis(IPA)while remission induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia. Liposomal amphotericin B improved the fungal serodiagnostic markers, however,the IPA worsened. She also developed an Aspergillus brain abscess,which, while being undetectable on CT,was detected as multiple nodular lesions by MRI. A definitive diagnosis was made by polymerase chain reaction(PCR)of brain biopsy specimens. Voriconazole(VRCZ)was effective,and cord blood transplantation was performed. She has received VRCZ for a long time. There are no relapse of either the IPA or the Aspergillus brain abscess.
Assuntos
Abscesso Encefálico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Aspergilose Pulmonar Invasiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antifúngicos , Feminino , Humanos , Aspergilose Pulmonar Invasiva/complicações , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , VoriconazolRESUMO
Autologous peripheral blood stem cell transplantation(auto-PBSCT)combined with high-dose chemotherapy has been considered as the standard therapy for relapsed or induction therapy-refractory aggressive lymphomas sensitive to chemotherapy. While various regimens have been applied as the conditioning,none has yet been established as the standard. We have begun to employ high-dose ranimustine,cytarabine,etoposide and cyclophosphamide(MCVAC)regimen. The present study was undertaken to review the efficacy and safety of MCVAC. Regimen: We carried out a retrospective analysis of 20 patients diagnosed as diffuse large B-cell lymphoma. The median follow-up duration of 20 patients was 13.05 months(range, 0.57-49.5 months). The 4-year OS and PFS were 57.8% and 30.2%,respectively. Relapse was the most frequent cause of treatment failure(n=7). The major toxicities were anorexia/nausea(95%),diarrhea (75%),hypokalemia (70%). One patient died of hepatic veno-occlusive disease(VOD). The serious adverse events included hypokalemia,arrhythmia,cerebral hemorrhage,and heart failure(1 case[5%]each). There was 1 case of a late-onset adverse event: therapy-related myelo- dysplastic syndrome/acute myeloblastic leukemia(MDS/AML). MCVAC regimen was concluded as effective and well-toler- ated. However,we should carefully monitored for the possible development of VOD and MDS/AML. Further follow-up is needed to evaluate the long-term efficacy and safety.
Assuntos
Linfoma Difuso de Grandes Células B , Transplante de Células-Tronco de Sangue Periférico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Etoposídeo , Humanos , Linfoma Difuso de Grandes Células B/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
Searching the 3D structural fragments of organic molecules is challenging because of structural differences between X-ray and theoretically calculated geometries and the conformational flexibility of substituents. The codification program called Conformational Code for Organic Molecules (CCOM) can be used to unambiguously convert 3D conformational data for various molecules to 1D data. Two deviations from Rule E-5.6 of the International Union of Pure and Applied Chemistry (IUPAC) Rules for Nomenclature of Organic Chemistry were introduced to the CCOM program for 3D fragment searching. First, the search for the highest priority atom was limited to a distance of two bonds from the center bond for dihedral angle determination. Second, for indistinguishable atoms in experimentally observed solution structures, the smallest number of atom index in the molecular model was chosen as the priority atom for dihedral angle determination. A search of the 3D conformational fragment mb_3a6c4c of mevastatin () in combination with the SMiles ARbitrary Target Specification (SMARTS) description suggested that a change in the conformation of this fragment may be the driving force for dissociation of mevastatin from its target protein. Chirality 28:370-375, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Lovastatina/análogos & derivados , Conformação Molecular , Software , Lovastatina/química , Estrutura MolecularRESUMO
BACKGROUND: Cotyledonoid dissecting leiomyoma (Sternberg tumor) is a rare variant of the uterine smooth muscle tumor. Although this tumor is a benign tumor clinically and pathologically, the appearance and growth pattern is unusual, so it may be misdiagnosed as malignancy. CASE REPORTS: We report two cases of cotyledonoid dissecting leiomyoma of the uterus that occurred in two 44- and 31-year-old women, respectively. Total hysterectomy and bilateral salpingo-oophorectomy were performed in one of the patients, and myomectomy was done in the other one. Macroscopically, both tumors were grape-like exophytic masses resembling placental tissue. The patients were well after surgery, and one patient gave birth. To our knowledge, this is the first case report of a successful delivery after myomectomy of this tumor. CONCLUSION: To prevent aggressive surgery it is important to recognize that this tumor is a benign and unusual appearing variant of leiomyoma. A fertility-sparing surgical procedure should be considered if the patient wishes to preserve her fertility.
Assuntos
Leiomioma/cirurgia , Tumor de Músculo Liso/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Tubas Uterinas/cirurgia , Feminino , Humanos , Histerectomia/métodos , Leiomioma/patologia , Ovariectomia/métodos , Gravidez , Tumor de Músculo Liso/patologia , Miomectomia Uterina/métodos , Neoplasias Uterinas/patologiaRESUMO
This study elucidates functional artificial luciferases (ALucs) wholly synthesized for bioassays and molecular imaging. The ALucs bearing epitopes were newly created by amending the sequences of our previously reported ALucs in light of a multi-sequence alignment and hydrophobicity search. The synthesized ALucs are survived in live cells and stable in culture media for 25 days after secretion. The epitopes in ALucs are exposed during the secretion process and indeed valid for column purification and immunological assays. The ALucs exerted a 9400-times stronger optical intensity with a coelenterazine derivative (CTZ i), when compared with Renilla reniformis luciferase 8.6-535. A supersecondary structure of ALuc30 was predicted with respect to the X-ray crystallographic information of the coelenterazine-binding protein (CBP). The structure revealed that ALuc30 has a room for accommodating the iodide of CTZ i. This study guides on how to create functional artificial luciferases and predicts the structural details with the current bioinformatics technologies.
Assuntos
Luciferases/química , Luciferases/genética , Medições Luminescentes/métodos , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Células COS , Chlorocebus aethiops , Estabilidade Enzimática , Epitopos/química , Epitopos/genética , Luciferases/biossíntese , Modelos Moleculares , Imagem Molecular , Dados de Sequência Molecular , Fenômenos Ópticos , Engenharia de Proteínas , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Alinhamento de Sequência , Especificidade por SubstratoRESUMO
Extralobar pulmonary sequestration (EPS) can occasionally be found incidentally in congenital diaphragmatic hernia (CDH). Extralobar pulmonary sequestration usually arises in the chest or the abdomen; rarely in the diaphragm. We report a neonatal case of antenatally diagnosed CDH associated with intradiaphragmatic EPS.
Assuntos
Sequestro Broncopulmonar/complicações , Sequestro Broncopulmonar/cirurgia , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/cirurgia , Sequestro Broncopulmonar/diagnóstico , Feminino , Seguimentos , Hérnias Diafragmáticas Congênitas/diagnóstico , Humanos , Achados Incidentais , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Diagnóstico Pré-Natal/métodos , Resultado do Tratamento , Ultrassonografia Pré-Natal/métodosRESUMO
Candida auris infection has been recognized as an urgent threat to antifungal drug resistance, and the Eagle effect of C. auris FKS1 (1,3-ß-d-glucan synthase) wild-type isolates has also been noted. The Eagle effect, namely, where higher concentrations of antifungals reduce fungicidal activity relative to lower concentrations, is a confounding factor of apparent antifungal resistance, but the detailed mechanism remains unclear. Here, we present the conformational variability of mutation sites for ERG11p (lanosterol 14α-demethylase) and FKS1 from deep neural network-based prediction along with the reported X-ray crystallographic and cryo-electron microscopy (cryo-EM) structures of antifungals. The sequence variability maps provide valuable insights into the inconsistent correlation between azole resistance and the mysterious Eagle effect with the dispersion of minimal inhibitory concentration (MIC) for echinocandin resistance. The conformational variability prediction supports the hypothesis that mutations K143R of clade I, VF125AL of clade III, and Y132F of clade IV for C. auris ERG11p make the corresponding site variable and that an increased population of invisible variable conformations potentially contributes to triazole resistance. In contrast, the predicted rigid conformation by the S639F mutation of hot spot region 1 (HS1) for FKS1 suggests that caspofungin (CAS) is involved in an uncompetitive inhibition, and a decreased population of the CAS-bound state of FKS1 with Rho1 leads to drug resistance. The predicted variable HS1 region for FKS1 WT isolates and the rigid one for FKS1 S639F mutants support the in vivo drug response and the in vitro MIC dispersion. A plausible mechanism of the Eagle effect is hereby proposed, namely, that a high concentration of CAS with a high membrane affinity reduces the population of the CAS-bound state of FKS1 with Rho1, as well as accompanying events such as aggregation or association depending on the conformational variability of HS1.
RESUMO
Previous studies indicate that the most common result of mixing two odors is the decreased olfactory perception of one or both components in the mixture. An excellent example of this phenomenon is provided by the masking of an unpleasant odor by a pleasant odor. This study hypothesized that dimethyl sulfide (DS; a major chemical component of oral malodor) might be masked by citronellal, a monoterpene aldehyde that produces an intense lemon aroma. To investigate this hypothesis, mice were chosen as odor sensor animals. Mice were trained in a Y maze to discriminate between DS (10 ppm in aqueous solution) and water. A series of generalization tests revealed that these trained "odor sensor" mice could also distinguish between 1 ppm DS and water, but not between 0.1 ppm DS and water. The mice were then confronted with the original choice of 10 ppm DS and water, but now in the presence of various concentrations of citronellal. The mice failed to detect the odor of DS when confronted with 30 ppm citronellal. The mice were similarly confused when confronted with citral (90 ppm) or limonene (3000 ppm). This study is the first to show that citrus odorants can mask the odor of DS, altering the behavioral responses of trained odor sensor mice.
Assuntos
Aldeídos/farmacologia , Cicloexenos/farmacologia , Monoterpenos/farmacologia , Odorantes , Percepção Olfatória/efeitos dos fármacos , Sulfetos , Terpenos/farmacologia , Monoterpenos Acíclicos , Aldeídos/química , Animais , Cicloexenos/química , Limoneno , Camundongos , Modelos Animais , Estrutura Molecular , Monoterpenos/química , Percepção Olfatória/fisiologia , Sulfetos/química , Terpenos/químicaRESUMO
It is shown that fuzzy search and data mining techniques of supersecondary structure homology for subunits of proteins using conformational code patterns of α-helix-type (3ß5α4ß) and ß-sheet-type (6α4ß4ß) fragments can be used to extract correlations between fragments of MHC class I molecules and the light chain of immunoglobulins. The new method of conformational pattern analysis with fuzzy search of structural code homology reflects well the shape of main chain rather than secondary structure in comparison with the DSSP method. Further, the data mining technique using the combination of h- and s-fragment patterns can quantify the supersecondary structure homology between any subunits of proteins with different amino acid sequences. Characteristic fragment patterns (string "shhshss"), which were sandwiched between two identical amino acid sequences His and Pro, were found in light chains of various types of immunogloblins, α-chain and ß-2 microglobulin of MHC class I and α-chain and ß-chain of MHC class II, but not in heavy chains of Fab immunoglobulin fragments and T cell receptors (TCR). Leukocyte immunoglobulin-like receptors (LILR) are related by the conformational fragment (string "shhshss") to ß-2 microglobulins as a type of pair forms (string "sohsss"). Further, human IgM rheumatoid factor, one of the immunogloblins, did not strongly exhibit the conformational fragment pattern. Nonclassic MHC class I molecules CD1D, MIC-A, and MIC-B, which have functions to activate NKT, NK, and T cells, did not also clearly show the patterns. These code-driven mining techniques can be utilized as a metadata-generating tool for systems biology to elucidate the biological function of such conformational fragments of MHC I and II molecules, which come in contact with various signal ligands on the surface of T cells and natural killer cells.
Assuntos
Mineração de Dados/métodos , Imunoglobulina M/química , Imunoglobulinas/química , Complexo Principal de Histocompatibilidade , Fator Reumatoide/química , Sequência de Aminoácidos , Animais , Cristalografia por Raios X , Lógica Fuzzy , Humanos , Imunoglobulina G/química , Cadeias Leves de Imunoglobulina/química , Camundongos , Modelos Moleculares , Fragmentos de Peptídeos/química , Conformação Proteica , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/efeitos dos fármacosRESUMO
Planctomycetes are ubiquitous in marine environment and were reported to occur in association with multicellular eukaryotic organisms such as marine macroalgae and invertebrates. Here, we investigate planctomycetes associated with the marine sponge Niphates sp. from the sub-tropical Australian coast by assessing their diversity using culture-dependent and -independent approaches based on the 16S rRNA gene. The culture-dependent approach resulted in the isolation of a large collection of diverse planctomycetes including some novel lineages of Planctomycetes from the sponge as well as sediment and seawater of Moreton Bay where this sponge occurs. The characterization of these novel planctomycetes revealed that cells of one unique strain do not possess condensed nucleoids, a phenotype distinct from other planctomycetes. In addition, a culture-independent clone library approach identified unique planctomycete 16S rRNA gene sequences closely related to other sponge-derived sequences. The analysis of tissue of the sponge Niphates sp. showed that the mesohyl of the sponge is almost devoid of microbial cells, indicating this species is in the group of 'low microbial abundant' (LMA) sponges. The unique planctomycete 16S rRNA gene sequences identified in this study were phylogenetically closely related to sequences from LMA sponges in other published studies. This study has revealed new insights into the diversity of planctomycetes in the marine environment and the association of planctomycetes with marine sponges.
Assuntos
Bactérias/classificação , Bactérias/genética , Poríferos/microbiologia , Animais , Austrália , Bactérias/ultraestrutura , Baías/microbiologia , Sedimentos Geológicos/microbiologia , Filogenia , Poríferos/ultraestrutura , RNA Ribossômico 16S , Água do Mar/microbiologiaRESUMO
The Omicron BA.1 variant of SARS-CoV-2 preferentially infects through the cathepsin-mediated endocytic pathway, but the mechanism of cell entry has not been solved yet because BA.4/5 is more fusogenic and more efficiently spread in human lung cells than BA.2. It has been unclear why the Omicron spike is inefficiently cleaved in virions compared with Delta, and how the relatively effective reproduction proceeds without the cell entry through plasma membrane fusion. Conformational variability from deep neural network-based prediction correlates well with the thermodynamic stability of variants. The difference of seasonable pandemic variants in summer and those in winter is distinguishable by this conformational stability, and the geographical optimization of variants is also traceable. Further, the predicted conformational variability maps rationalize the less efficient S1/S2 cleavage of Omicron variants and provide a valuable insight into the cell entry through the endocytic pathway. It is concluded that conformational variability prediction is able to complement transformation information on motifs in protein structures for drug discovery.