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Introduction. Maternal screening tests and prophylactic antibiotics are important to prevent neonatal and infant group B streptococcal (GBS) infections.Hypothesis/Gap Statement. The performance of enrichment broth media for GBS screening that are available in Japan is unclear. Whole-genome data of GBS isolates from pregnant women in Japan is lacking.Aim. The aim of this study was to compare the protocol performance of six enrichment broths and two subculture agar plates, which were all available in Japan, for GBS detection. In addition, we showed whole-genome data of GBS isolates from pregnant women in Japan.Methodology. We collected 133 vaginal-rectal swabs from pregnant women visiting clinics and hospitals in Nagasaki Prefecture, Japan, and compared the protocol performance of 6 enrichment broths and 2 subculture agar plates. All GBS isolates collected in this study were subjected to whole-genome sequencing analysis.Results. We obtained 133 vaginal-rectal swabs from pregnant women at 35-37 weeks of gestation from 8 private clinics and 2 local municipal hospitals within Nagasaki Prefecture, Japan. The detection rate of the protocol involving the six enrichment broths and subsequent subcultures varied between 95.5 and 100â%, depending on the specific choice of enrichment broth. The GBS carriage rate among pregnant women in this region was 18.8â%. All 25 isolates derived from the swabs were susceptible to penicillin, whereas 48 and 36â% of the isolates demonstrated resistance to erythromycin and clindamycin, respectively. The distribution of serotypes was highly diverse, encompassing seven distinct serotypes among the isolates, with the predominant serotype being serotype V (n = 8). Serotype V isolates displayed a tendency towards increased resistance to erythromycin and clindamycin, with all resistant isolates containing the ermB gene.Conclusion. There was no difference in performance among the culture protocols evaluated in this study. GBS strains isolated from pregnant women appeared to have greater genomic diversity than GBS strains detected in neonates/infants with invasive GBS infections. To confirm this result, further studies with larger sample sizes are needed.
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Antibacterianos , Infecções Estreptocócicas , Streptococcus agalactiae , Vagina , Humanos , Streptococcus agalactiae/genética , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificação , Streptococcus agalactiae/classificação , Feminino , Gravidez , Japão/epidemiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/epidemiologia , Antibacterianos/farmacologia , Vagina/microbiologia , Meios de Cultura/química , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/epidemiologia , Reto/microbiologia , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , Adulto , Clindamicina/farmacologia , Genoma BacterianoRESUMO
Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.
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RATIONALE: Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation. PATIENTS CONCERNS: A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced. DIAGNOSIS: Based on the course of the illness and imaging findings, the patient was diagnosed with AFE. INTERVENTIONS: By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications. OUTCOMES: By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae. LESSONS: VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved.
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Embolia Amniótica , Oxigenação por Membrana Extracorpórea , Humanos , Feminino , Embolia Amniótica/terapia , Embolia Amniótica/diagnóstico , Oxigenação por Membrana Extracorpórea/métodos , Adulto , Gravidez , Cesárea/efeitos adversos , Transfusão de Sangue/métodos , Ácido Tranexâmico/uso terapêutico , Ácido Tranexâmico/administração & dosagem , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/terapia , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagemRESUMO
The primary mode of infection by human T-cell leukemia virus type 1 (HTLV-1) is cell-to-cell transmission during contact between infected cells and target cells. Cell-free HTLV-1 infections are known to be less efficient than infections with other retroviruses, and transmission of free HTLV-1 is considered not to occur in vivo. However, it has been demonstrated that cell-free HTLV-1 virions can infect primary lymphocytes and dendritic cells in vitro, and that virions embedded in biofilms on cell membranes can contribute to transmission. The establishment of an efficient cell-free HTLV-1 infection model would be a useful tool for analyzing the replication process of HTLV-1 and the clonal expansion of infected cells. We first succeeded in obtaining supernatants with high-titer cell-free HTLV-1 using a highly efficient virus-producing cell line. The HTLV-1 virions retained the structural characteristics of retroviruses. Using this cell-free infection model, we confirmed that a variety of cell lines and primary cultured cells can be infected with HTLV-1 and demonstrated that the provirus was randomly integrated into all chromosomes in the target cells. The provirus-integrated cell lines were HTLV-1-productive. Furthermore, we demonstrated for the first time that cell-free HTLV-1 is infectious in vivo using a humanized mouse model. These results indicate that this cell-free infection model recapitulates the HTLV-1 life cycle, including entry, reverse transcription, integration into the host genome, viral replication, and secondary infection. The new cell-free HTLV-1 infection model is promising as a practical resource for studying HTLV-1 infection.IMPORTANCECo-culture of infected and target cells is frequently used for studying HTLV-1 infection. Although this method efficiently infects HTLV-1, the cell mixture is complex, and it is extremely difficult to distinguish donor infected cells from target cells. In contrast, cell-free HTLV-1 infection models allow for more strict experimental conditions. In this study, we established a novel and efficient cell-free HTLV-1 infection model. Using this model, we successfully evaluated the infectivity titers of cell-free HTLV-1 as proviral loads (copies per 100 cells) in various cell lines, primary cultured cells, and a humanized mouse model. Interestingly, the HTLV-1-associated viral biofilms played an important role in enhancing the infectivity of the cell-free infection model. This cell-free HTLV-1 infection model reproduces the replication cycle of HTLV-1 and provides a simple, powerful, and alternative tool for researching HTLV-1 infection.
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Sistema Livre de Células , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Animais , Humanos , Camundongos , Infecções por HTLV-I/transmissão , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/crescimento & desenvolvimento , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Linfócitos/virologia , Provírus/genética , Provírus/metabolismo , Replicação Viral , Sistema Livre de Células/virologia , Linhagem Celular , Células Cultivadas , Internalização do Vírus , Transcrição Reversa , Biofilmes , Integração ViralRESUMO
BACKGROUND: In Japan, genetic testing, surveillance, and risk-reducing surgery for hereditary breast and ovarian cancer (HBOC) syndrome have been covered by the Japanese national insurance system since April 2020. On the other hand, the current situation is that medical care, including surveillance of undiagnosed (cancer-free) patients, is self-funded even for individuals with HBOC. We report a case in which breast cancer was diagnosed at an early stage during surveillance for cancer-free HBOC at the patient's own expense, and risk-reducing surgery was performed at the same time as treatment for breast cancer. CASE PRESENTATION: The patient was a 63-year-old woman. Her sister had a history of breast cancer in her 30s and was found to be a BRCA2 pathogenic variant carrier by genetic testing. The patient therefore presented to the genetic department of our hospital and underwent genetic testing (out-of-pocket). A pathogenic variant was found at the same site. During annual breast and ovarian surveillance at the patient's own expense, a physician with sufficient expertise in contrast-enhanced breast magnetic resonance imaging (MRI) noticed a change in the contrast enhancement pattern on breast MRI and performed needle biopsy, revealing ductal carcinoma in situ. At the request of the patient, she underwent concurrent contralateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy in addition to breast cancer treatment. CONCLUSIONS: We encountered a case in which cancer treatment and risk-reducing surgery were performed at the same time for a pathogenic variant carrier who was very anxious about developing cancer. Surveillance of cancer-free BRCA1/2 mutation carriers and expansion of insurance coverage for surgery are important future issues.
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IMPORTANCE: The World Health Organization estimated that 5-10 million people are infected with human T-cell leukemia virus type 1 (HTLV-1). This number is likely to be underestimated because reliable endemic data are available for only approximately 1.5 billion people worldwide. The point-of-care test is a powerful tool for the easy and quick detection of infections without the requirement for expensive instruments and laboratory equipment. Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test that was evaluated in this study, might significantly advance our understanding of the global epidemiology of HTLV-1 infection.
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Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologiaRESUMO
Human papillomavirus (HPV) types included in the genus alpha papillomavirus (alpha-HPVs) are subdivided into high- and low-risk HPVs associated with tumorigenicity. According to conventional risk classification, over 30 alpha-HPVs remain unclassified and HPV groups phylogenetically classified using the L1 gene do not exactly correspond to the conventional risk classification groups. Here, we propose a novel cervical lesion progression risk classification strategy. Using four E6 risk distinguishable amino acids (E6-RDAAs), we successfully expanded the conventional classification to encompass alpha-HPVs and resolve discrepancies. We validated our classification system using alpha-HPV-targeted sequence data of 325 cervical swab specimens from participants in Japan. Clinical outcomes significantly correlated with the E6-RDAA classification. Four of five HPV types in the data set that were not conventionally classified (HPV30, 34, 67, and 69) were high-risk according to our classification criteria. This report sheds light on the carcinogenicity of rare genital HPV types using a novel risk classification strategy.
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Aminoácidos , Infecções por Papillomavirus , Humanos , Papillomavirus Humano , Papillomaviridae/genética , Japão/epidemiologiaRESUMO
One of the fundamental applications for monolayer-thick 2D materials is their use as protective layers of metal surfaces and in situ intercalated reactive materials in ambient conditions. Here we investigate the structural, electronic, and magnetic properties, as well as the chemical stability in air of a very reactive metal, Europium, after intercalation between a hexagonal boron nitride (hBN) layer and a Pt substrate. We demonstrate that Eu intercalation leads to a hBN-covered ferromagnetic EuPt2 surface alloy with divalent Eu2+ atoms at the interface. We expose the system to ambient conditions and find a partial conservation of the di-valent signal and hence the Eu-Pt interface. The use of a curved Pt substrate allows us to explore the changes in the Eu valence state and the ambient pressure protection at different substrate planes. The interfacial EuPt2 surface alloy formation remains the same, but the resistance of the protecting hBN layer to ambient conditions is reduced, likely due to a rougher surface and a more discontinuous hBN coating.
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BACKGROUND: Androgen-producing granulosa cell tumor in adolescent girl is rare condition and clinical characteristics are not fully elucidated. CASE PRESENTATION: Seventeen years old girl complained of secondary amenorrhea was referred to our out-patient consultation. Markedly elevated serum testosterone, LH, and AMH levels were noted. Mild hirsutism and clitoromegaly were presented. Transabdominal ultrasonography and MRI revealed cystic mass occupied pelvic cavity probably originated from left ovary. Right ovary showed polycystic appearance. Laparoscopic left ovarian cystectomy was performed. After the surgery, her menstruation resumed along with normalized hormonal parameters, and clinical hyperandrogenism were improved. Since the scarcity of cellular lining of inner cyst wall, definitive pathological diagnosis was difficult. After the consultation with gynecological pathologist, the tumor was diagnosed as sex cord stromal tumor, highly suspicious for adult granulosa cell tumor. Residual left salpingo-oophorectomy was performed by additional laparoscopic surgery. Her serum testosterone and AMH levels were remained low with regular menstrual cycles and no evidence of recurrence. CONCLUSIONS: Androgen-producing cystic granulosa cell tumor is rare gynecological disorders, which need both gynecologic oncological and endocrinological approach. Its clinical manifestations may bring some clues to the pathogenesis of ovulatory dysfunctions, such as polycystic ovary syndrome.
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Tumor de Células da Granulosa , Neoplasias Ovarianas , Síndrome do Ovário Policístico , Adolescente , Feminino , Humanos , Androgênios , Tumor de Células da Granulosa/diagnóstico , Tumor de Células da Granulosa/cirurgia , Tumor de Células da Granulosa/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/cirurgia , Síndrome do Ovário Policístico/complicações , TestosteronaRESUMO
Substituting carbon with silicon in organic molecules and materials has long been an attractive way to modify their electronic structure and properties. Silicon-doped graphene-based materials are known to exhibit exotic properties, yet conjugated organic materials with atomically precise Si substitution have remained difficult to prepare. Here we present the on-surface synthesis of one- and two-dimensional covalent organic frameworks whose backbones contain 1,4-disilabenzene (C4Si2) linkers. Silicon atoms were first deposited on a Au(111) surface, forming a AuSix film on annealing. The subsequent deposition and annealing of a bromo-substituted polyaromatic hydrocarbon precursor (triphenylene or pyrene) on this surface led to the formation of the C4Si2-bridged networks, which were characterized by a combination of high-resolution scanning tunnelling microscopy and photoelectron spectroscopy supported by density functional theory calculations. Each Si in a hexagonal C4Si2 ring was found to be covalently linked to one terminal Br atom. For the linear structure obtained with the pyrene-based precursor, the C4Si2 rings were converted into C4Si pentagonal siloles by further annealing.
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Background: Human T-cell leukemia virus type-1 (HTLV-1) is transmitted vertically from an infected mother to her child via breastfeeding during infancy or horizontally via sexual contact. However, little information is available on the HTLV-1 seroconversion rate in pregnant mothers and the impact of new HTLV-1 infection on mothers and babies during the perinatal period. Methods: From the database of a prefecture-wide antenatal adult T-cell leukemia prevention program in Nagasaki, Japan, we extracted data on 57,323 pregnant women who were screened for anti-HTLV-1 antibody during 2011-2018. Data on the 16,863 subjects whose HTLV-1 proviral load (PVL) was measured more than twice were included in our analyses. Results: In total, 133 (0.79%) pregnant women were HTLV-1-positive during their first pregnancy and nine (0.05%) seroconverted before or during subsequent pregnancies (between pregnancies). The median PVL (per 100 peripheral blood mononuclear cells) was significantly lower in the seroconverted mothers (0.10%) than in the initially seropositive mothers (0.15%). A repeated measures correlation analysis for the individual PVLs of the HTLV-1-positive pregnant women showed that PVL increased with parity number (rrm = 0.25) with no perinatal problems. Conclusion: The HTLV-1 seroconversion rate between pregnancies was 0.05%, and their HTLV-1 PVL increased annually but no perinatal problems were noted.
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BACKGROUND/AIM: The aim of this study was to clarify the biological differences between ovarian cancer-associated fibroblasts (OCa-CAFs) and normal ovary-derived mesenchymal stem cells (NO-MSCs). MATERIALS AND METHODS: Surgically resected ovarian cancer and contralateral normal ovarian tissue samples were cut into small pieces for culture as "explants". The number of outgrown cells, their proliferative kinetics, and expression levels of cell surface markers of CAFs, as well as three miRNAs in OCa-CAFs and NO-MSCs were compared directly. Differentially expressed genes between both groups were also investigated. RESULTS: Comparable numbers of outgrown cells were harvested from both groups. Significantly higher expression of α-smooth muscle actin and miR-142 was found in OCa-CAFs, which decreased significantly during ex vivo cell expansion. A total of 21 differentially expressed genes were identified between both groups. CONCLUSION: OCa-CAFs showed different biological properties in direct comparison with NO-MSCs, which might play major roles in the pathogenesis of ovarian cancer.
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Fibroblastos Associados a Câncer , Células-Tronco Mesenquimais , MicroRNAs , Neoplasias Ovarianas , Fibroblastos Associados a Câncer/metabolismo , Feminino , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/patologiaRESUMO
We applied photoemission tomography (PT) to a unique one-dimensional row structure of a picene multilayer realized on an anisotropic Ag(110) surface. Taking advantage of the simplified structure of the multilayer film, we successfully deconvoluted the photoelectron momentum maps of three frontier orbitals of picene. Thereafter, the clearly deconvoluted experimental momentum maps were compared to the Fourier transform simulation of the molecular orbitals of picene in detail, enabling not only the evaluation of the electronic structure of the picene in the multilayer but also the determination of the molecular orientation in the multilayer within a few degrees. In addition, the PT results indicated the orientation of the molecules in all layers to be flat-lying. The successful demonstration of PT of the multilayer molecular film marks an important step toward the wide-range utilization of the PT technique.
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OBJECTIVE: As coronavirus disease 2019 (COVID-19) rages on, it is a challenging task to balance resources for treatment of COVID-19 and malignancy-based treatment. For the development of optimal strategies, assessing the conditions and constrains in treatment during the COVID-19 pandemic is pertinent. This study reported about a nationwide survey conducted by the Japan Society of Gynecologic Oncology. METHODS: We interviewed 265 designated training facilities about the state of their clinical practice from the time period between March and December 2020. We asked the facility doctors in charge to fill a web-based questionnaire. RESULTS: A total of 232 facilities (87.5%) responded. A decrease in the number of outpatient visits was reported, and the major reason attributed was reluctance of patients to visit hospitals rather than facility restrictions. The actual number of surgeries decreased by 3.9%, compared to 2019. There was a significant difference when the variable of "Prefectures operating under special safety precautions" or not was introduced. There was no increase in the rate of advanced stages in the three cancer types studied. However, 34.1% participants perceived COVID-19 affected management and prognosis. CONCLUSION: Refraining from visiting hospitals based on the patient's judgment may be expected to be an issue in the future. No significant decrease in surgeries was observed, and it would seem that there were few forced changes in treatment plans, but "the State of Emergency" had an impact. There was no increase in the rate of advanced cancers, but this will need to be monitored.
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COVID-19 , Neoplasias , Feminino , Humanos , Japão/epidemiologia , Pandemias , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
Electronic charge rearrangement between components of a heterostructure is the fundamental principle to reach the electronic ground state. It is acknowledged that the density of state distribution of the components governs the amount of charge transfer, but a notable dependence on temperature is not yet considered, particularly for weakly interacting systems. Here, it is experimentally observed that the amount of ground-state charge transfer in a van der Waals heterostructure formed by monolayer MoS2 sandwiched between graphite and a molecular electron acceptor layer increases by a factor of 3 when going from 7 K to room temperature. State-of-the-art electronic structure calculations of the full heterostructure that accounts for nuclear thermal fluctuations reveal intracomponent electron-phonon coupling and intercomponent electronic coupling as the key factors determining the amount of charge transfer. This conclusion is rationalized by a model applicable to multicomponent van der Waals heterostructures.
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Gestational diabetes mellitus (GDM) is known to be a significant risk factor for the future development of type 2 diabetes. Here, we investigated whether a precise evaluation of ß- and α-cell functions helps to identify women at high risk of developing glucose intolerance after GDM. Fifty-six women with GDM underwent a 75-g oral glucose tolerance test (OGTT) at early (6-12 weeks) postpartum. We measured their concentrations of glucose, insulin, proinsulin and glucagon at fasting and 30, 60 and 120 min. At 1-year post-delivery, we classified the women into a normal glucose tolerance (NGT) group or an impaired glucose tolerance (IGT)/diabetes mellitus (DM) group. Forty-three of the 56 women completed the study. At 1-year post-delivery, 17 women had developed IGT/DM and 26 women showed NGT. In the early-postpartum OGTTs, the IGT/DM group showed a lower insulinogenic index, a less glucagon suppression evaluated by the change from fasting to 30 min (ΔGlucagon 30 min), and a higher glucagon-to-insulin ratio at 30 min compared to the NGT group. There were no significant between-group differences in proinsulin levels or proinsulin-to-insulin ratios. Insulinogenic index <0.6 and ΔGlucagon 30 min >0 pg/mL were identified as predictors for the development of IGT/DM after GDM, independent of age, body mass index, and lactation intensity. These results suggest that the bihormonal disorder of insulin and glucagon causes the postpartum development of glucose intolerance. The measurement of plasma insulin and glucagon during the initial OGTT at early postpartum period can help to make optimal decisions regarding the postpartum management of women with GDM.
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Glicemia , Diabetes Gestacional/sangue , Glucagon/sangue , Intolerância à Glucose/sangue , Insulina/sangue , Adulto , Índice de Massa Corporal , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina/fisiologia , Gravidez , Estudos ProspectivosRESUMO
Human T cell leukemia virus type 1 (HTLV-1) is mainly transmitted vertically through breast milk. The rate of mother-to-child transmission (MTCT) through formula feeding, although significantly lower than through breastfeeding, is approximately 2.4%-3.6%, suggesting the possibility of alternative transmission routes. MTCT of HTLV-1 might occur through the uterus, birth canal, or placental tissues; the latter is known as transplacental transmission. Here, we found that HTLV-1 proviral DNA was present in the placental villous tissues of the fetuses of nearly half of pregnant carriers and in a small number of cord blood samples. An RNA ISH assay showed that HTLV-1-expressing cells were present in nearly all subjects with HTLV-1-positive placental villous tissues, and their frequency was significantly higher in subjects with HTLV-1-positive cord blood samples. Furthermore, placental villous trophoblasts expressed HTLV-1 receptors and showed increased susceptibility to HTLV-1 infection. In addition, HTLV-1-infected trophoblasts expressed high levels of viral antigens and promoted the de novo infection of target T cells in a humanized mouse model. In summary, during pregnancy of HTLV-1 carriers, HTLV-1 was highly expressed in placental villous tissues, and villous trophoblasts showed high HTLV-1 sensitivity, suggesting that MTCT of HTLV-1 occurs through the placenta.
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Infecções por HTLV-I/metabolismo , Vírus Linfotrópico T Tipo 1 Humano/metabolismo , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez/metabolismo , Trofoblastos/metabolismo , Adulto , Células Cultivadas , Feminino , Infecções por HTLV-I/patologia , Infecções por HTLV-I/transmissão , Humanos , Gravidez , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Trofoblastos/patologia , Trofoblastos/virologiaRESUMO
As p53-binding protein 1 (53BP1) localizes to the sites of DNA double-strand breaks and rapidly forms nuclear foci (NF), and its presence may be an indicator of endogenous genomic instability (GIN). We previously showed that 53BP1 NF in cervical cells increase with neoplastic progression, indicating the significance of 53BP1 expression for the estimation of malignant potential during cervical carcinogenesis. This study aimed to further elucidate the impact of 53BP1 expression as a biomarker for cervical squamous intraepithelial lesion (SIL). A total of 81 tissue samples, including 17 of normal cervical epithelium, 22 of cervical intraepithelial neoplasia (CIN) 1, 21 of CIN2, and 21 of CIN3, from patients positive for high-risk human papillomavirus (HR-HPV) were used for double-label immunofluorescence of 53BP1 and Ki-67/p16INK4a expression and HR-HPV in situ hybridization. We analyzed associations between 53BP1 expression type with parameters such as CIN grade, HR-HPV infection status, p16INK4a expression, and CIN prognosis. Expression type of 53BP1 was significantly associated with histological grade of CIN and HR-HPV in situ hybridization signal pattern (P < .0001). There was a significant correlation between 53BP1 and p16INK4a expression levels (r = .73, P < .0001). However, there was no association between 53BP1 expression type and CIN prognosis. We propose that 53BP1 expression type is a valuable biomarker for SIL, which can help estimate the grade and GIN of cervical lesions reflecting replication stress caused by the integration of HR-HPV to the host genome.
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Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Infecções por Papillomavirus/metabolismo , Lesões Intraepiteliais Escamosas/metabolismo , Lesões Intraepiteliais Escamosas/virologia , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/biossíntese , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Adulto , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Humanos , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas/genética , Lesões Intraepiteliais Escamosas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
AIMS/INTRODUCTION: The role of glucagon abnormality has recently been reported in type 2 diabetes; however, its role in gestational diabetes mellitus (GDM) is still unknown. The glucose intolerance in GDM is heterogeneous, and not all patients require insulin treatment during pregnancy. Here, we investigated whether glucagon abnormality is associated with the requirement for insulin treatment during pregnancy. MATERIALS AND METHODS: A total of 49 pregnant women diagnosed with GDM were enrolled. They underwent a 75-g oral glucose tolerance test during mid-gestation, and we measured their plasma glucagon levels (by a new sandwich enzyme-linked immunosorbent assay) at fasting (0 min), and at 30, 60 and 120 min after glucose load in addition to the levels of plasma glucose and serum insulin. All participants underwent another oral glucose tolerance test at postpartum. RESULTS: Of the 49 patients, 15 required insulin treatment (Insulin group) and 34 were treated with diet therapy alone until delivery (Diet group). The early-phase glucagon secretion after glucose load, as determined by the changes in glucagon from the baseline to 30 min, was paradoxically augmented during mid-gestation in the Insulin group, but not in the Diet group. The impaired glucagon suppression during mid-gestation in the Insulin group was not associated with insulin secretory/sensitivity indexes studied, and was ameliorated postpartum, although the plasma glucose levels remained higher in the Insulin group versus the Diet group. CONCLUSIONS: Impaired early-phase suppression of glucagon could be associated with the requirement for insulin treatment during pregnancy in patients with GDM.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Gestacional/tratamento farmacológico , Glucagon/metabolismo , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adulto , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Feminino , Seguimentos , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Gravidez , Prognóstico , Estudos ProspectivosRESUMO
Highly oriented, multilayer molecular films of picene and dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) molecules with the long axis parallel to the substrate (parallel configuration, hereafter) were fabricated on their characteristic bulklike monolayer. These molecules form a dense monolayer with a bulklike molecular arrangement on metal surfaces such as Au(111), which allows further stacking of parallel molecules. Indeed, upon adsorption of picene and DNTT on these dense monolayers, growth of straight islands of multilayer without the dendritic layer was observed. Particularly, in the case of picene, one-dimensional islands with lengths over 100 µm were formed and aligned in 3-fold symmetric directions of the substrate, which was not observed in the case of DNTT. X-ray diffraction measurements revealed the presence of [201Ì ] and [211Ì ] planes and the absence of the [001] diffractions, indicating that the one-dimensional islands of picene indeed consist of parallel molecules. The formation of huge crystalline islands in the case of picene, in contrast to the case of DNTT, is likely induced by the stronger intermolecular force, as suggested from the calculation of the vibrational energy.