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1.
Microb Pathog ; 182: 106243, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37422175

RESUMEN

Leptospira enters humans and animals through injured skin or mucous membranes by direct or indirect contact with urine excreted from infected reservoirs. Individuals with cut or scratched skin are at high risk of infection and are recommended to be protected from contact with Leptospira, but the risk of infection via skin without apparent wounds is unknown. We hypothesized that the stratum corneum of the epidermis might prevent percutaneous invasion of leptospires. We established a stratum corneum deficient model of hamsters using the tape stripping method. The mortality rate of hamsters lacking stratum corneum that were exposed to Leptospira was higher than that of controls with shaved skin, and was not significantly different from an epidermal wound group. These results indicated that the stratum corneum plays a critical role in protecting the host against leptospiral entry. We also examined the migration of leptospires through the monolayer of HaCaT cells (human keratinocyte cell line) using Transwell. The number of pathogenic leptospires penetrating the HaCaT cell monolayers was higher than that of non-pathogenic leptospires. Furthermore, scanning and transmission electron microscopic observations revealed that the bacteria penetrated the cell monolayers through both intracellular and intercellular routes. This suggested that pathogenic Leptospira can migrate easily through keratinocyte layers and is associated with virulence. Our study further highlights the importance of the stratum corneum as a critical barrier against the invasion of Leptospira found in contaminated soil and water. Hence, preventative measures against contact infection should be taken, even without visible skin wounds.


Asunto(s)
Leptospira interrogans , Leptospira , Leptospirosis , Cricetinae , Animales , Humanos , Leptospirosis/microbiología , Epidermis/patología , Piel/patología
2.
Ann Surg Oncol ; 30(8): 5267-5277, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37222942

RESUMEN

BACKGROUND: The prognosis for patients with colorectal cancer (CRC) is determined by tumor characteristics as well as the host immune response. This study investigated the relationship between an immunosuppressive state and patient prognosis by evaluating the systemic and tumor microenvironment (TME) interleukin (IL)-6 levels. METHODS: Preoperative serum IL-6 levels were measured using an electrochemiluminescence assay. Expression of IL-6 in tumor and stromal cells was evaluated immunohistochemically in 209 patients with resected CRC. Single-cell analysis of tumor-infiltrating immune cells was performed using mass cytometry in 10 additional cases. RESULTS: Elevated serum IL-6 levels were associated with elevated stromal IL-6 levels and a poor prognosis for patients with CRC. High IL-6 expression in stromal cells was associated with low-density subsets of CD3+ and CD4+ T cells as well as FOXP3+ cells. Mass cytometry analysis showed that IL-6+ cells among tumor-infiltrating immune cells were composed primarily of myeloid cells and rarely of lymphoid cells. In the high-IL-6-expression group, the percentages of myeloid-derived suppressor cells (MDSCs) and CD4+FOXP3highCD45RA- effector regulatory T cells (eTreg) were significantly higher than in the low-IL-6-expression group. Furthermore, the proportion of IL-10+ cells in MDSCs and that of IL-10+ or CTLA-4+ cells in eTregs correlated with IL-6 levels. CONCLUSION: Elevated serum IL-6 levels were associated with stromal IL-6 levels in CRC. High IL-6 expression in tumor-infiltrating immune cells also was associated with accumulation of immunosuppressive cells in the TME.


Asunto(s)
Neoplasias Colorrectales , Interleucina-10 , Humanos , Neoplasias Colorrectales/metabolismo , Factores de Transcripción Forkhead/metabolismo , Interleucina-10/metabolismo , Interleucina-6 , Linfocitos Infiltrantes de Tumor , Pronóstico , Microambiente Tumoral
4.
Neurol Med Chir (Tokyo) ; 63(5): 213-219, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36754418

RESUMEN

We describe a three-step, simple binostril approach to endoscopic endonasal transsphenoidal surgery in cases of sellar/parasellar lesions. In the first step, the mucosa of the lower third of the ethmoid bulla on the outside was coagulated with monopolar microdissection needle and opened to create space on the outside of the middle turbinate. The middle turbinate was moved outward using this space, and the natural ostium of the sphenoid sinus could be confirmed easily. In the second step, a less than 10 mm incision was made from the right natural ostium of the sphenoid sinus to the right nasal septal mucosa. The anterior wall of the sphenoid sinus was removed to free the sphenoid sinus. In the third step, the instrument was inserted through the left nostril using a hole connected to the natural ostium of the sphenoid sinus to reach the sellar floor via both nostrils. It took longer for the trainee than for the instructor to reach the sellar floor in the first four cases. However, there was no significant difference in the approach time after the fifth case. Approach-related postoperative complications were observed in 52 cases of sellar/parasellar lesions performed. This approach was considered to provide sufficient space and was simple and less burdensome to the patient.


Asunto(s)
Endoscopía , Neoplasias Hipofisarias , Humanos , Endoscopía/efectos adversos , Cavidad Nasal/patología , Cavidad Nasal/cirugía , Cornetes Nasales , Seno Esfenoidal/cirugía , Seno Esfenoidal/patología , Complicaciones Posoperatorias/etiología , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología
5.
Pharm Res ; 40(3): 711-719, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36720832

RESUMEN

PURPOSE: Information on milk transferability of drugs is important for patients who wish to breastfeed. The purpose of this study is to develop a prediction model for milk-to-plasma drug concentration ratio based on area under the curve (M/PAUC). The quantitative structure-activity/property relationship (QSAR/QSPR) approach was used to predict compounds involved in active transport during milk transfer. METHODS: We collected M/P ratio data from literature, which were curated and divided into M/PAUC ≥ 1 and M/PAUC < 1. Using the ADMET Predictor® and ADMET Modeler™, we constructed two types of binary classification models: an artificial neural network (ANN) and a support vector machine (SVM). RESULTS: M/P ratios of 403 compounds were collected, M/PAUC data were obtained for 173 compounds, while 230 compounds only had M/Pnon-AUC values reported. The models were constructed using 129 of the 173 compounds, excluding colostrum data. The sensitivity of the ANN model was 0.969 for the training set and 0.833 for the test set, while the sensitivity of the SVM model was 0.971 for the training set and 0.667 for the test set. The contribution of the charge-based descriptor was high in both models. CONCLUSIONS: We built a M/PAUC prediction model using QSAR/QSPR. These predictive models can play an auxiliary role in evaluating the milk transferability of drugs.


Asunto(s)
Leche , Relación Estructura-Actividad Cuantitativa , Humanos , Animales , Redes Neurales de la Computación
6.
Anticancer Res ; 43(2): 613-620, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36697107

RESUMEN

BACKGROUND/AIM: Chemotherapy combined with anti-EGFR or anti-VEGF monoclonal antibodies (mAb) is widely used to treat patients with metastatic colorectal cancer (mCRC). Here, we investigated the effects of these antibodies on T-cell infiltration and T-cell receptor (TCR) repertoire variation in CRC liver metastases. MATERIALS AND METHODS: Ten patients with mCRC received chemotherapy in combination with anti-EGFR (n=6) or anti-VEGF (n=4) mAb. T-cell infiltration was examined for CD3 and CD8 by carrying out immunohistochemistry on biopsy or surgical specimens from liver metastases before and after treatment. TCR repertoire analysis was carried out on specimens with post-treatment CD3+ T-cell infiltration. RESULTS: T-cell infiltrations were approximately 83% (5/6) and 50% (2/4), following treatment with anti-EGFR or anti-VEGF mAb, respectively. TCR repertoire analysis revealed higher clonality and lower diversity of TCR alpha and beta (TRA and TRB) in the anti-VEGF mAb group than that in the anti-EGFR group mAb. Furthermore, the percentage of the common TCR clones between infiltrating T cells and T cells in peripheral blood was significantly lower in the anti-VEGF mAb group compared to that in the anti-EGFR mAb group. CONCLUSION: The population of T cells infiltrating liver metastases in the anti-VEGF mAb group differed from that in the anti-EGFR mAb group.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Linfocitos T , Anticuerpos Monoclonales/farmacología , Receptores de Antígenos de Linfocitos T alfa-beta , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Receptores de Antígenos de Linfocitos T
7.
Anticancer Res ; 43(1): 105-114, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36585204

RESUMEN

BACKGROUND/AIM: Colorectal cancer is the third most common cancer globally, and the poor prognosis of patients with metastatic colorectal cancer (mCRC) warrants urgent attention. We previously obtained 10 candidate serum biomarkers for mCRC. Our aim with this study was to determine the prognostic performance of the pre-treatment serum C-C motif chemokine ligand 7 (CCL7) concentration in patients with mCRC. PATIENTS AND METHODS: Protein concentrations of CCL7 were examined using ELISA and immunohistochemistry for serum (n=110) and surgical specimens (n=85), respectively, of patients with mCRC. The relationship between protein concentration and prognosis was examined using Cox regression analysis, receiver operator characteristic curve analysis and the Kaplan-Meier method. RESULTS: The overall survival (OS) of patients with high concentrations of serum CCL7 was significantly poorer than that of patients with low concentrations. Patients with a high CCL7 concentration in the stroma had significantly poorer outcomes than those with a low concentration. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 were significantly higher in the high-CCL7 group, compared to those in the low-CCL7 group. Univariate and multivariate analysis revealed that serum CCL7 concentration was a significant prognostic factor for mCRC. The combination of serum CCL and CEA concentrations was also useful in this regard (area under the curve=0.71). CONCLUSION: The combined pre-treatment serum levels of CCL7 and CEA are useful prognostic biomarkers for mCRC.


Asunto(s)
Quimiocina CCL7 , Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Biomarcadores de Tumor , Antígeno Carcinoembrionario , Quimiocina CCL7/sangre , Quimiocina CCL7/química , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/metabolismo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/metabolismo , Ligandos , Pronóstico , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/metabolismo , Estudios Retrospectivos
8.
Cancer Med ; 12(4): 4294-4305, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36308049

RESUMEN

OBJECTIVE: Irinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecan-associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A. METHODS: A total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel. Genome-wide screening was performed using whole-exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe. RESULTS: Using WES after a doublet chemotherapy regimen comprising irinotecan and 5-fluorouracil (n = 15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan-associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled-coil containing 1 (R3HCC1; c.919G > A, rs2272761) showed a significant association with neutropenia (>grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n = 23) or modified FOLFIRINOX for pancreatic cancer (n = 40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p = 0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan-free regimens, FOLFOX for mCRC (n = 66), and gemcitabine plus nab-paclitaxel for pancreatic cancer (n = 47). CONCLUSION: Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neutropenia , Neoplasias Pancreáticas , Neoplasias del Recto , Humanos , Irinotecán , Polimorfismo de Nucleótido Simple , Camptotecina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Fluorouracilo , Neoplasias del Colon/tratamiento farmacológico , Neutropenia/inducido químicamente , Neoplasias del Recto/tratamiento farmacológico , Leucovorina/efectos adversos , Neoplasias Pancreáticas
10.
BMC Cancer ; 22(1): 1071, 2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-36253752

RESUMEN

BACKGROUND: We recently reported the relapse-free survival (RFS) significance of the combination of CD4+ and forkhead box P3+ (FOXP3) T-cell densities identified by immunohistochemistry in patients with stage I, II, and III colorectal cancer (CRC) who underwent curative resections. This study was designed to determine the optimal combination of markers that predict recurrence in patients with T factors of T3/T4a stage II CRC by applying a novel Bayes decision rule. METHODS: Using 137 cancer tissue specimens from T3/T4a stage II patients, 12 clinicopathologic and immune factors were analysed as predictive candidates for recurrence. RESULTS: Our study showed that the combination of low CD4+ and low FOXP3+ T-cell densities resulted in extremely poor RFS. CONCLUSIONS: Adjuvant chemotherapy may be considered for patients with a combination of low CD4+ and low FOXP3+ T-cell densities. The discovery of this new prognostic indicator is important for the appropriate management of patients undergoing curative resection for T3/T4a stage II CRC.


Asunto(s)
Neoplasias Colorrectales , Factores de Transcripción Forkhead , Teorema de Bayes , Biomarcadores , Neoplasias Colorrectales/patología , Humanos , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico
11.
Gan To Kagaku Ryoho ; 49(9): 922-927, 2022 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-36156006

RESUMEN

Cancer immunotherapy including immune checkpoint inhibitors(ICIs)have established itself as the fourth cancer therapy. However, the response rate of ICIs is still only about 20%, and tumors resistant to ICIs are often so-called"cold-tumor"with low tumor immunogenicity. Therefore, research and development is being conducted worldwide on how to convert cold- tumors into hot-tumors with high immunogenicity. In this paper, we review the relationship between tumor immunogenicity and ICI, as well as therapeutic methods to enhance tumor immunogenicity, and introduce our research about novel cancer peptide vaccination therapy.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Antígenos de Neoplasias , Vacunas contra el Cáncer/uso terapéutico , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias/terapia , Vacunas de Subunidad/uso terapéutico
12.
Ann Surg Oncol ; 29(12): 7423-7433, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35876924

RESUMEN

BACKGROUND: Poor prognosis in liver cancer is due to its high frequency of intrahepatic metastasis. Cancer stem-like cells (CSLCs), which possess the properties of stemness, tumor initiation capability, and resistance to therapy, also exhibit metastatic potential. Immune surveillance plays an important role in the accomplishment of metastasis. Herein, the property of immune evasion in CSLCs was investigated. METHODS: Sphere cells were induced as CSLCs using a sphere induction medium containing neural survival factor-1. The expression of genes involved in immune evasion was determined using RNA-sequencing for sphere and parental cells followed by validation using flow cytometric analysis and ELISA. Susceptibility to natural killer (NK) cell-mediated cytotoxicity was examined by a chromium release assay. A xenograft model using BALB/c nu/nu mice was used to assess tumor growth. Gene set enrichment analysis was performed for interpreting RNA sequencing. RESULTS: The cell surface expressions of PD-L1, PD-L2, and CEACAM1 were upregulated and those of ULBP1 and MICA/MICB were downregulated in SK-sphere, CSLCs derived from SK-HEP-1, compared with that in parental cells. Levels of soluble MICA were elevated in conditioned medium from SK-sphere. Expression of HLA class I was not downregulated in SK-sphere. The susceptibilities to NK cell-mediated killing and secreted perforin were significantly lower in both CSLCs derived from SK-HEP-1 and HLE than in parental cells. Tumors formed upon inoculation of SK-sphere in immunodeficient mice harboring NK cells were larger than those formed upon inoculation of parental cells. CONCLUSION: Human hepatoma cell line-derived CSLCs may possess immune evasion properties, especially from NK cell-mediated immunity.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Antígeno B7-H1 , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Cromo , Medios de Cultivo Condicionados , Humanos , Evasión Inmune , Células Asesinas Naturales , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Perforina , ARN
13.
Ann Clin Biochem ; 59(6): 396-403, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35821582

RESUMEN

BACKGROUND: Although faecal DNA testing of Fusobacterium nucleatum (Fn) is expected to be useful for colorectal neoplasia detection, there is no standardized quantification method of Fn. We performed this study to establish a possible standardized method. METHODS: In this study, 322 participants including 71 subjects without colorectal neoplasia (control group), 31 patients with non-advanced colorectal adenoma, 93 patients with advanced colorectal adenoma, and 127 patients with colorectal cancer were enrolled. Faecal Fn were quantified by droplet digital PCR (ddPCR) using two PCR primer-probe sets reported previously that are tentatively named Fn1 and Fn2. Fn1 has been used in ddPCR by us and Fn2 has been widely used in quantitative real-time PCR. RESULTS: The Fn copy number using Fn1 was five times higher than that using Fn2, with a linear relationship shown between them. Receiver operating characteristic curve analysis showed the area under the curve (AUC) to be almost the same between Fn1 and Fn2 in discriminating between the control group and the colorectal cancer group (AUC = 0.81 and 0.81, respectively), and between the control/non-advanced colorectal adenoma group and the advanced colorectal adenoma/colorectal cancer group (AUC = 0.74 and 0.74, respectively). CONCLUSIONS: As the diagnostic performance was quite similar between Fn1 and Fn2, ddPCR-based Fn testing using Fn1 and Fn2 could be a possible standardized method for a colorectal neoplasia screening test, considering that Fn levels quantified by Fn1 are about five times higher than those by Fn2.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Humanos , Fusobacterium nucleatum/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/microbiología , Heces/microbiología , Adenoma/diagnóstico , Adenoma/genética , Adenoma/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa
14.
BMC Cancer ; 22(1): 260, 2022 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-35277124

RESUMEN

BACKGROUND: Cancer stem cells (CSCs) are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) which possess enhanced chemoresistance and metastatic potential. To enable the development of targeted therapy against CSLCs, we identified a gene responsible for this phenotype in CSLC. METHODS: Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique sphere inducing medium, and HuH-7 cells were used as non-sphere forming cells in the same condition. RNA-sequencing was performed followed by validation with quantitative RT-PCR and western blotting. Knockdown experiments were done by using CRISPR-Cas9 genome-editing, and the rescue experiments were performed using the expressing plasmid vector. Chemoresistance and liver metastasis of the cells, was studied following the splenic injection of cells to severely immune deficient mice and evaluated using the MTS assay. Quantification of exosomes in the medium was done using ELISA. RESULTS: RAB3B was identified as an up-regulated gene in both CSLCs and prognostically poor hepatocellular carcinoma (HCC) by RNA-sequencing. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion was observed in CSLCs, and it was not observed in the RAB3B-KD cells. In addition, the RAB3B expression correlated with the expression of ABCG2, APOE, LEPR, LXN, and TSPAN13. CONCLUSION: The up regulation of RAB3B may play an important role in the chemoresistance and metastatic potential of CSLCs.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Células Madre Neoplásicas/metabolismo , Proteínas de Unión al GTP rab3/metabolismo , Animales , Carcinogénesis/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Hepáticas/patología , Ratones , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba
15.
Surg Neurol Int ; 13: 30, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35242396

RESUMEN

BACKGROUND: The use of the exoscope has been increasing in the field of neurosurgery, as it can set the visual axis freely, enabling the surgeon to operate in a comfortable posture. Although endoscope-assisted surgery for compensation of insufficient surgical field is useful under the microscope, we report that using an endoscope in exoscopic surgery is safer and more useful. METHODS: The exoscope used was ORBEYE. All surgical procedures were performed exoscopically from the beginning of the surgery. When endoscopic observation was required during the operation, the endoscope was inserted under observation by an exoscope. The exoscopic screen was 4K-3D and endoscopic screen was 4K-2D, the operation was performed while observing both screens at the same time. The endoscope was held manually or by a mechanical holder. RESULTS: Twenty-two cases, including 14 requiring microvascular decompression (MVD) and eight requiring tumor removal, were performed by endoscopic-assisted exoscopic surgery. The endoscope could be inserted safely because its relationship with the surrounding structure could be observed under the exoscope, and the operator could observe both screens without moving the head. Fourteen of 22 patients required additional endoscopic treatment. Satisfactory two-handed operation was performed in 13 cases. Symptomatology disappeared in all cases of MVD, and sufficient tumor resection was achieved. CONCLUSION: Exoscopic surgery provides excellent surgical view that is not inferior to conventional microsurgery. As a large space can be secured between the scope and the surgical field, it is safer and easier to manipulate the endoscope under the exoscope.

16.
Microbiol Spectr ; 10(2): e0215721, 2022 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-35289672

RESUMEN

Leptospirosis is a zoonotic disease caused by infection with pathogenic leptospires. Consistent with recent studies by other groups, leptospires were isolated from 89 out of 110 (80.9%) soil or water samples from varied locations in the Philippines in our surveillance study, indicating that leptospires might have a life cycle that does not involve animal hosts. However, despite previous work, it has not been confirmed whether leptospires multiply in the soil environment under various experimental conditions. Given the fact that the case number of leptospirosis is increased after flood, we hypothesized that waterlogged soil, which mimics the postflooding environment, could be a suitable condition for growing leptospires. To verify this hypothesis, pathogenic and saprophytic leptospires were seeded in the bottles containing 2.5 times as much water as soil, and bacterial counts in the bottles were measured over time. Pathogenic and saprophytic leptospires were found to increase their number in waterlogged soil but not in water or soil alone. In addition, leptospires were reisolated from soil in closed tubes for as long as 379 days. These results indicate that leptospires are in a resting state in the soil and are able to proliferate with increased water content in the environment. This notion is strongly supported by observations that the case number of leptospirosis is significantly higher in rainy seasons and increased after flood. Therefore, we reached the following conclusion: environmental soil is a potential reservoir of leptospires. IMPORTANCE Since research on Leptospira has focused on pathogenic leptospires, which are supposed to multiply only in animal hosts, the life cycle of saprophytic leptospires has long been a mystery. This study demonstrates that both pathogenic and saprophytic leptospires multiply in the waterlogged soil, which mimics the postflooding environment. The present results potentially explain why leptospirosis frequently occurs after floods. Therefore, environmental soil is a potential reservoir of leptospires and leptospirosis is considered an environment-borne as well as a zoonotic disease. This is a significant report to reveal that leptospires multiply under environmental conditions, and this finding leads us to reconsider the ecology of leptospires.


Asunto(s)
Leptospira , Leptospirosis , Animales , Leptospirosis/epidemiología , Leptospirosis/veterinaria , Suelo , Agua , Zoonosis/epidemiología , Zoonosis/microbiología
17.
Gan To Kagaku Ryoho ; 49(13): 1609-1612, 2022 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-36733151

RESUMEN

The patient is a 65-year-old woman. Colonoscopy performed for close examination of constipation and lower abdominal pain revealed a circumferential type 3 lesion in the rectum Ra. A CT scan showed invasion of the primary lesion into the extramural and sacral front and multiple metastases in the mesorectal lymph nodes but no distant metastasis. Staging laparoscopy was performed. As the mesorectum around the primary lesion was tightly adherent, it was difficult to R0 resection; hence, only construction of colostomy was performed. We have introduced chemotherapy(FOLFOXIRI plus bevacizumab therapy), and 4 courses were administered. Post-treatment CT scan showed that the peri-invasiveness of the primary tumor had disappeared and the enlarged lymph nodes had shrunk. Furthermore, SUVmax of PET-CT for main lesion was decreased, dramatically. On day 109 after the initial surgery, laparoscopic low anterior resection was performed. Although the left hypogastric nerve was resected, other areas could be dissected and R0 resection could be performed. FOLFOXIRI therapy has shown good early-tumor shrinkage and depth of response and may be useful for patients with locally advanced rectal cancer who have difficulty securing circumferential resection margin(CRM).


Asunto(s)
Neoplasias del Recto , Recto , Femenino , Humanos , Anciano , Recto/patología , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
18.
Gan To Kagaku Ryoho ; 49(13): 1494-1496, 2022 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-36733113

RESUMEN

The patient is a woman in her 80s who underwent a partial gastrectomy for a gastric GIST 14 years ago. This time, she presented our department with upper abdominal distention and computed tomography revealed an 18 cm-sized cystic lesion in the left lobe of the liver. Since a nodule enhancement was observed in the cyst, malignant disease such as hepatic cystadenocarcinoma could not be ruled out and surgical resection was performed. Pathological examination revealed liver metastasis of gastric GIST. In Japan, only 14 cases have been reported showing such late recurrence with liver metastasis more than 10 years after resection of a primary tumor, including our case. In addition, the cystic finding in this case made preoperative diagnosis difficult because a needle biopsy could not be performed to obtain a pathological diagnosis.


Asunto(s)
Quistes , Tumores del Estroma Gastrointestinal , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Femenino , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Neoplasias Hepáticas/secundario , Hepatectomía , Quistes/cirugía , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología
19.
Viruses ; 13(10)2021 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-34696394

RESUMEN

Bacteriophages are viruses that specifically infect bacteria and are classified as either virulent phages or temperate phages. Despite virulent phages being promising antimicrobial agents due to their bactericidal effects, the implementation of phage therapy depends on the availability of virulent phages against target bacteria. Notably, virulent phages of Streptococcus gordonii, which resides in the oral cavity and is an opportunistic pathogen that can cause periodontitis and endocarditis have previously never been found. We thus attempted to isolate virulent phages against S. gordonii. In the present study, we report for the first time a virulent bacteriophage against S. gordonii, ΦSG005, discovered from drainage water. ΦSG005 is composed of a short, non-contractile tail and a long head, revealing Podoviridae characteristics via electron microscopic analysis. In turbidity reduction assays, ΦSG005 showed efficient bactericidal effects on S. gordonii. Whole-genome sequencing showed that the virus has a DNA genome of 16,127 bp with 21 coding sequences. We identified no prophage-related elements such as integrase in the ΦSG005 genome, demonstrating that the virus is a virulent phage. Phylogenetic analysis indicated that ΦSG005 forms a distinct clade among the streptococcus viruses and is positioned next to streptococcus virus C1. Molecular characterization revealed the presence of an anti-CRISPR (Acr) IIA5-like protein in the ΦSG005 genome. These findings facilitate our understanding of streptococcus viruses and advance the development of phage therapy against S. gordonii infection.


Asunto(s)
Genoma Viral , Filogenia , Fagos de Streptococcus/genética , Fagos de Streptococcus/patogenicidad , Streptococcus gordonii/virología , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Terapia de Fagos , Fagos de Streptococcus/clasificación , Virulencia , Secuenciación Completa del Genoma
20.
Surg Laparosc Endosc Percutan Tech ; 31(5): 608-612, 2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34618787

RESUMEN

BACKGROUND: Complete rectal prolapse (CRP) commonly affects the daily life of older people and has no established operative treatment approach. We describe our simple method of laparoscopic, sutureless rectopexy, involving rectal mobilization (along with its peritoneum bilaterally) and fixation to the sacral promontory using a fixation device. We also present an analysis of short-term outcomes in patients treated using this procedure. MATERIALS AND METHODS: We retrospectively evaluated 62 patients with CRP, who underwent a laparoscopic rectopexy via tack fixation, between 2004 and 2017. The peritoneum was widely attached near the site of peritoneal reflection, as in rectal cancer surgery. The hypogastric nerve was carefully detached from the front of the sacrum. Keeping the nerve intact, we lifted and mobilized the dissected rectum cranially towards the promontory, and the rectal peritoneum was affixed to the sacrum by applying 2 to 3 fixed tacks bilaterally, using a fixation device. RESULTS: The median age of the study group was 80 (10 to 91) years. All procedures were successful without serious intraoperative complications; only 1 patient required conversion to open surgery. Median values for operative duration, intraoperative blood loss, and postoperative period of hospitalization were 177 (125 to 441) minutes, 5 (0 to 275) mL, and 7 (3 to 17) days, respectively. Only 6 (9.7%) patients experienced recurrence during the follow-up period. CONCLUSION: Laparoscopic tacking rectopexy performed using a fixation device for repairing CRP is a simple, safe, and sutureless procedure with no severe complications or mortality.


Asunto(s)
Laparoscopía , Prolapso Rectal , Anciano , Anciano de 80 o más Años , Humanos , Prolapso Rectal/cirugía , Recto/cirugía , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
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