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1.
BMC Infect Dis ; 24(1): 180, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336644

RESUMO

BACKGROUND: Pseudomonas nitroreducens is a non-fermenting, gram-negative, rod-shaped bacterium commonly inhabiting soil, particularly soil contaminated with oil brine. To our knowledge, no cases of human infection with P. nitroreducens have been previously reported. Here, we present the first documented case of cholangitis caused by P. nitroreducens in a patient with bacteremia. CASE PRESENTATION: A 46-year-old Japanese man with an advanced pancreatic neuroendocrine tumor was hospitalized with fever and chills. Four days before admission, the patient developed right upper abdominal pain. Two days later, he also experienced fever and chills. Endoscopic retrograde cholangiopancreatography was performed on the day of admission, and the patient was diagnosed as having cholangitis associated with stent dysfunction. Gram-negative rods were isolated from blood cultures, but attempts to identify the bacteria using VITEK2 and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with VITEK MS ver. 4.7.1 (bioMérieux Japan Co. Ltd., Tokyo, Japan) were unsuccessful. Finally, the organism was identified as P. nitroreducens using MALDI-TOF MS with a MALDI Biotyper (Bruker Daltonics Co., Ltd., Billerica, MA, USA) and 16 S ribosomal RNA sequencing. Despite thorough interviews with the patient, he denied any exposure to contaminated soil. The patient was treated with intravenous cefepime and oral ciprofloxacin for 16 days based on susceptibility results, achieving a good therapeutic outcome. At the outpatient follow-up on day 28, the patient was in good general condition. CONCLUSIONS: This is the first reported human case of cholangitis with bloodstream infection caused by P. nitroreducens. This report provides clinicians with novel insights into the clinical manifestations and diagnostic methods necessary for the accurate diagnosis of P. nitroreducens, along with guidance on treatment.


Assuntos
Bacteriemia , Colangite , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Masculino , Humanos , Pessoa de Meia-Idade , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bactérias , Pseudomonas , Bactérias Aeróbias , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Colangite/tratamento farmacológico , Colangite/etiologia , Solo
2.
J Infect Chemother ; 30(8): 800-805, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38272263

RESUMO

Mycobacterium mageritense (M. mageritense), a nontuberculous mycobacterium, is classified as a rapidly growing mycobacterium, class IV in the Runyon Classification. This bacterium is found in soil, water, and other habitats. Infections caused by M. mageritense are relatively rare and no treatment protocol has been established. Herein, we report a case of skin and soft tissue infection caused by M. mageritense. A 49-year-old woman underwent surgery for right breast cancer. Four months after surgery, a surgical site infection was found, and M. mageritense was identified in the wound culture using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Based on the sensitivity results, the patient was treated with levofloxacin and doxycycline for 4 months. In addition to antimicrobial agents, aggressive surgical interventions led to a favorable course of treatment. In conclusion, successful treatment of skin and soft tissue infections with M. mageritense requires surgical intervention whenever possible, aggressive susceptibility testing, and appropriate antimicrobial therapy.


Assuntos
Antibacterianos , Neoplasias da Mama , Levofloxacino , Infecções por Mycobacterium não Tuberculosas , Infecção da Ferida Cirúrgica , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/cirurgia , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/diagnóstico , Antibacterianos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Levofloxacino/uso terapêutico , Doxiciclina/uso terapêutico , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/efeitos dos fármacos , Mycobacterium/isolamento & purificação , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/cirurgia , Infecções dos Tecidos Moles/terapia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Resultado do Tratamento
3.
J Infect Chemother ; 30(11): 1170-1174, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38552839

RESUMO

Salmonella enterica subspecies enterica serovar Choleraesuis (S. Choleraesuis) is a nontyphoidal Salmonella pathogen that causes swine paratyphoids. S. Choleraesuis is a zoonotic pathogen transmitted to humans via contaminated food and causes sepsis. Here, we report a rare case of pyelonephritis caused by S. Choleraesuis in a Japanese patient with a carcinoma of unknown primary origin. On the day of admission, the patient was diagnosed with pyelonephritis associated with ureteral stent obstruction. He had no history of raw pork consumption or gastrointestinal symptoms. Gram-negative rods were isolated from urine and blood cultures, identified as Salmonella enterica subsp. enterica using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The serological typing results were O7: -: 1 and 5; however, the serotypes could not be determined. The isolate was identified as S. Choleraesuis using multilocus sequence typing, nucleotide sequence analysis of the fliC gene, and biochemical examination. Four days after a 14-day course of intravenous piperacillin-tazobactam (9 g/day), the patient showed relapse of the condition. Subsequently, the patient was treated with intravenous ceftriaxone (2 g/day) and oral amoxicillin (1000 mg/day) for 14 days each; recurrence was not observed. This novel case of pyelonephritis with bacteremia was caused by S. Choleraesuis in Japan. Conventional testing methods could not identify the serotypes; however, the case highlights the importance of adopting advanced diagnostic techniques based on molecular biology to ensure accurate pathogen identification.


Assuntos
Antibacterianos , Bacteriemia , Pielonefrite , Infecções por Salmonella , Idoso , Humanos , Masculino , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/diagnóstico , População do Leste Asiático , Japão , Tipagem de Sequências Multilocus , Neoplasias Primárias Desconhecidas/microbiologia , Neoplasias Primárias Desconhecidas/complicações , Combinação Piperacilina e Tazobactam/uso terapêutico , Pielonefrite/microbiologia , Pielonefrite/diagnóstico , Pielonefrite/tratamento farmacológico , Salmonella enterica/isolamento & purificação , Infecções por Salmonella/microbiologia , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/tratamento farmacológico
4.
Int J Clin Oncol ; 29(11): 1696-1703, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39187737

RESUMO

BACKGROUND: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers. METHODS: Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts. RESULTS: There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes. CONCLUSIONS: We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Reparo de Erro de Pareamento de DNA , Humanos , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reparo de Erro de Pareamento de DNA/genética , Detecção Precoce de Câncer/métodos , Testes Genéticos , Idade de Início , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Adulto Jovem
5.
J Genet Couns ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367595

RESUMO

Huntington's disease (HD) is a neurodegenerative disease with autosomal dominant inheritance, and no radical cure for HD has been established. Qualitative studies are necessary to investigate the psychological state of individuals who underwent predictive testing for HD, because the psychosocial impact on noncarriers remains unclarified in Japan. Herein, we elucidated the psychosocial impact on the noncarriers for HD and the role of genetic counseling for predictive testing and follow-up after testing by examining their experiences with predictive testing. We conducted semi-structured interviews with eight individuals participating in this study. Interview data were transcribed verbatim and evaluated according to thematic analysis. As a result, 4 themes were generated from 21 categories of 46 codes: (1) Diversity of perceptions concerning the test results, (2) Views on life as a noncarrier, (3) Changes in feelings toward and relationships with family members, and (4) Sharing information within the family. After receiving the negative results, the noncarriers felt not only relief but also surprise, doubt, relief from tension, and regret. It was shown that noncarriers felt survivor's guilt toward many unspecified individuals, which was not only a sense of guilt but also a sense of mission or responsibility. Additionally, they conducted altruistic behavior as members of their family and society, that may be related to the Japanese collectivism. Some participants were concerned about sharing information with their siblings. Noncarriers for HD can experience complex psychological states, and Japanese people who prefer high-context communication may find it difficult to express their feelings and thoughts. It is important to understand their true feelings before and after the predictive genetic testing, reconsider the impact of being a noncarrier and whether it is a burden for them from both subjective and objective perspectives, and conduct long-term follow-up as needed.

6.
BMC Infect Dis ; 22(1): 613, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836203

RESUMO

BACKGROUND: Campylobacter rectus is a gram-negative rod, and Parvimonas micra is a gram-positive coccus, both of which are oral anaerobes that cause chronic periodontitis. Chronic periodontitis can cause bacteremia and systemic diseases, including osteomyelitis. Hematogenous osteomyelitis caused by anaerobic bacteria is uncommon, and to date, there have been no reports of mixed bacteremia with C. rectus and P. micra. Here, we report the first case of osteomyelitis of the femur caused by anaerobic bacteria with mixed bacteremia of C. rectus and P. micra caused by chronic periodontitis. CASE PRESENTATION: A 75-year-old man with chronic periodontitis, hyperuricemia, and benign prostatic hyperplasia was admitted to the hospital with a fracture of the left femur. The patient had left thigh pain for 4 weeks prior to admission. Left femoral intramedullary nail fixation was performed, and a large amount of abscess and necrotic tissue was found intraoperatively. The cultures of abscess specimens were identified as P. micra, Fusobacterium nucleatum, and C. rectus. C. rectus and P. micra were also isolated from blood cultures. C. rectus was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16 S ribosomal RNA sequencing. Sulbactam-ampicillin was administered for approximately 1 month, after which it was replaced by oral clavulanic acid-amoxicillin for long-term suppressive treatment. CONCLUSIONS: Only five cases of bloodstream infection with C. rectus have been reported, and this is the first report of mixed bacteremia with P. micra. Clinicians should consider that chronic periodontitis caused by rare oral anaerobic bacteria can cause systemic infections, such as osteomyelitis.


Assuntos
Bacteriemia , Periodontite Crônica , Osteomielite , Abscesso/complicações , Idoso , Bacteriemia/complicações , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bactérias Anaeróbias , Campylobacter rectus/genética , Periodontite Crônica/complicações , Fêmur , Firmicutes , Humanos , Masculino , Osteomielite/complicações , Osteomielite/tratamento farmacológico , Peptostreptococcus
7.
BMC Infect Dis ; 22(1): 529, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672730

RESUMO

BACKGROUND: Pandoraea species are multidrug-resistant glucose-nonfermenting gram-negative bacilli that are usually isolated from patients with cystic fibrosis (CF) and from water and soil. Reports of diseases, including bloodstream infections, caused by Pandoraea spp. in non-CF patients are rare, and the clinical and microbiological characteristics are unclear. The identification of Pandorea spp. is limited by conventional microbiological methods and may be misidentified as other species owing to overlapping biochemical profiles. Here, we report the first case of obstructive cholangitis with bacteremia caused by Pandoraea apista in a patient with advanced colorectal cancer. A 61-year-old man with advanced colorectal cancer who underwent right nephrectomy for renal cell carcinoma 4 years earlier with well-controlled diabetes mellitus was admitted to our hospital with fever for 2 days. The last chemotherapy (regorafenib) was administered approximately 3 weeks ago, and an endoscopic ultrasound-guided hepaticogastrostomy was performed 2 weeks ago under hospitalization for obstructive jaundice. Two days prior, he presented with fever with chills. He was treated with piperacillin-tazobactam for obstructive cholangitis and showed improvement but subsequently presented with exacerbation. Bacterial isolates from the blood and bile samples were identified as P. apista using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal RNA sequencing. Based on the susceptibility results of the isolates, he was successfully treated with oral trimethoprim-sulfamethoxazole 160 mg/800 mg/day for 14 days for P. apista infection. CONCLUSIONS: Pandoraea species are often misidentified. Therefore, multiple approaches should be used to identify them, and decisions regarding antimicrobial treatment should be based on actual in vitro susceptibility. Only seven cases of Pandoraea spp. bloodstream infections have been reported, and we report the first case of cholangitis with bacteremia.


Assuntos
Bacteriemia , Colangite , Neoplasias Colorretais , Fibrose Cística , Sepse , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Burkholderiaceae , Colangite/tratamento farmacológico , Fibrose Cística/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico , RNA Ribossômico 16S/genética , Análise de Sequência de RNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
8.
J Infect Chemother ; 28(10): 1419-1423, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35718261

RESUMO

INTRODUCTION: Sphingobacterium is an aerobic, glucose non-fermenting, Gram-negative rod bacterium that has been isolated from soil, plants, food, and water sources, including in hospitals. Reports of systemic infections caused by Sphingobacterium multivorum (S. multivorum) are rare, and their clinical and microbiological characteristics remain unclear. Moreover, conventional microbiological methods have limited ability to identify S. multivorum. We report the first case of obstructive cholangitis with bacteremia caused by S. multivorum in a patient with gastric cancer. CASE REPORT: A 68-year-old woman with advanced gastric cancer, hypertension, and hyperlipidemia was admitted with obstructive jaundice, and subsequently developed obstructive cholangitis during the hospital stay. S. multivorum were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S ribosomal RNA sequencing of the patient's blood samples. Based on the antibiotic susceptibility results of the isolates, cefepime was administered intravenously for 14 days, with good therapeutic outcomes. CONCLUSIONS: S. multivorum infection is rare, and its microbiology and pathogenicity in humans is mostly unknown. Therefore, multiple diagnostic approaches should be used to identify S. multivorum, and antimicrobial therapy should be selected based on the in vitro susceptibility. This report provides clinicians with novel information on the clinical manifestations and diagnostic methods for an accurate diagnosis of S. multivorum.


Assuntos
Bacteriemia , Colangite , Sphingobacterium , Neoplasias Gástricas , Acinetobacter , Idoso , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Colangite/complicações , Colangite/tratamento farmacológico , Feminino , Humanos , RNA Ribossômico 16S/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sphingobacterium/genética , Neoplasias Gástricas/complicações
9.
Gan To Kagaku Ryoho ; 49(7): 761-767, 2022 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-35851347

RESUMO

Recently, pembrolizumab have been approved for advanced solid tumor with microsatellite instability-high, and nivolumab including combination therapy with ipilimumab for colorectal cancer with microsatellite instability-high, and usefulness of those 3 checkpoint inhibitors have been paid attention. Genetic testing is essential for selecting molecular-targeted drugs in colorectal cancer; however, the type of tests and their optimal timing are becoming more complicated. Hence, this article reviews the gene mutation tests used for advanced colorectal cancer, the molecular mechanism of colorectal cancer with microsatellite instability-high, the clinical development status of immune checkpoint inhibitors, and the future perspective on treatment strategy.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Testes Genéticos , Humanos , Inibidores de Checkpoint Imunológico , Ipilimumab/uso terapêutico
10.
BMC Infect Dis ; 21(1): 1052, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627188

RESUMO

BACKGROUND: Schizophyllum commune is a basidiomycete that lives in the environment and can cause infections, mainly those of the respiratory system. Although S. commune is increasingly reported as a cause of allergic bronchopulmonary mycosis and sinusitis, cases of fungal ball formation are extremely uncommon. Identification of S. commune is difficult using routine mycological diagnostic methods, and in clinically suspicious cases, internal transcribed spacer sequencing should be used for diagnosis. Here, we report a first case of lung cancer with a fungal ball formation of S. commune, confirmed by analyzing the internal transcribed spacer. CASE PRESENTATION: A 76-year-old man with diabetes and hypertension was admitted to the hospital with a chief complaint of hemosputum, which he had for about 19 months. A computed tomography image of the patient's chest showed a cavity and internal nodule in the left upper lobe of his lung. A left upper lobectomy was performed, and histopathological examination revealed squamous cell carcinoma of the lung and a fungal ball. The isolate from the surgical specimen was identified as S. commune by analyzing the internal transcribed spacer. The patient had no recurrence of the infection during 5 months of follow-up. CONCLUSIONS: Only three cases of lung fungal balls caused by S. commune have been previously reported, and this is the first case of lung cancer cavity with a fungal ball formation. In cases of fungal ball formation in the lung, S. commune should be considered a possible causative microorganism.


Assuntos
Aspergilose Pulmonar Invasiva , Neoplasias Pulmonares , Schizophyllum , Tuberculose Pulmonar , Idoso , Humanos , Masculino , Recidiva Local de Neoplasia , Schizophyllum/genética
11.
Biosci Biotechnol Biochem ; 86(1): 56-67, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34669931

RESUMO

In 2004, the US Department of Energy listed d-glucaric acid as one of the top 12 bio-based chemicals and a potential biopolymer building block. In this study, we show that Pseudogluconobacter saccharoketogenes strains can produce d-glucaric acid from d-glucose, although in low yield because of the generation of the byproduct 2-keto-d-gluconic acid in large quantities. To improve d-glucaric acid yield, we generated Rh47-3, a P. saccharoketogenes IFO14464 mutant, which produced d-glucaric acid from d-gluconic acid and d-glucose with 81 and 53 mol% yields, respectively. Furthermore, the key enzymes involved in d-glucaric acid production, alcohol dehydrogenase (Ps-ADH), aldehyde dehydrogenase (Ps-ALDH), and gluconate 2-dehydrogenase (Ps-GADH), were purified and their roles in d-glucaric acid synthesis were evaluated. Ps-ADH and Ps-ALDH catalyzed d-glucaric acid production, which was mediated by d-gluconic acid and d-glucuronic acid pathways. In contrast, Ps-GADH inhibited d-glucaric acid production by promoting the formation of 2-keto-d-gluconic acid from d-glucose.


Assuntos
Bactérias
12.
J Infect Chemother ; 27(9): 1360-1364, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33888421

RESUMO

BACKGROUND: Exophiala (Wangiella) dermatitidis is a clinically relevant black yeast. Although E. dermatitidis rarely causes human infection, it can cause superficial and deep-seated infections, and cutaneous and subcutaneous diseases. Cases of fungemia and central line-associated bloodstream infections due to E. dermatitidis are extremely uncommon, and their clinical manifestations and prognosis are still not well-known. Herein, we report a case of central line-associated bloodstream infections in a patient with cancer. These infections were caused by melanized yeast that was finally identified as E. dermatitidis via internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. CASE PRESENTATION: A 75-year-old man with thoracic esophageal cancer and early gastric cancer presented with a 1-day history of fever during his hospitalization at our hospital. A central venous port was placed in the patient for total parenteral nutrition. Two E. dermatitidis isolates were recovered from two blood samples drawn at different times from a peripheral vein and this central venous port. The isolate was identified as E. dermatitidis by internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The central venous port was removed, and the patient was administered micafungin and voriconazole. Although the minimum inhibitory concentrations of E. dermatitidis for voriconazole and minimum effective concentrations for micafungin were 2 µg/mL and 4 µg/m, respectively, the bacteremia was successfully treated. CONCLUSIONS: Although no clear treatment guidelines have been proposed for E. dermatitidis infections, immediate removal of central venous catheters is the key to improving central line-associated bloodstream infections.


Assuntos
Bacteriemia , Exophiala , Neoplasias , Idoso , Exophiala/genética , Humanos , Masculino , Neoplasias/complicações , Voriconazol
13.
J Infect Chemother ; 27(12): 1769-1773, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34400093

RESUMO

BACKGROUND: Salmonella infections are associated with gastroenteritis, enteric fever, bacteremia, focal infection, and chronic carrier state. Cases of Salmonella osteomyelitis are uncommon and mainly occur in individuals with immunosuppressive conditions. Herein, we report a case of Salmonella osteomyelitis that required differentiation from malignancy in an immunocompetent adult patient. CASE PRESENTATION: A 31-year-old previously healthy male truck driver presented with a 2-week history of pain in his left upper arm. He had fallen off the back of a truck 2 months previously and injured the left side of his body. He also had bloody diarrhea and fever. Computed tomography and magnetic resonance imaging revealed a lesion that appeared to be a bone tumor in the left humerus, and the patient was referred to our cancer center from another clinic. Culture of a biopsy specimen of the left humerus was negative; however, the consensus sequence in broad-range polymerase chain reaction (PCR) showed the highest similarity to the 16S rRNA gene of Salmonella enterica subspecies enterica. Curettage of the left humerus was performed, and the patient was administered levofloxacin for 6 weeks. He recovered left arm function and had no recurrence during 2 months of follow-up. CONCLUSIONS: When the culture of blood or biopsy specimens is negative in situations wherein a specific infection is suspected, broad-range PCR with sequencing should be considered to determine the causative organism.


Assuntos
Neoplasias , Osteomielite , Infecções por Salmonella , Salmonella enterica , Adulto , Humanos , Úmero , Masculino , Osteomielite/diagnóstico por imagem , Osteomielite/tratamento farmacológico , Reação em Cadeia da Polimerase , RNA Ribossômico 16S , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/tratamento farmacológico , Salmonella enterica/genética
14.
J Hum Genet ; 65(2): 125-132, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31628423

RESUMO

In tumor-only next-generation sequencing (NGS), identified variants have the potential to be secondary findings (SFs), but they require verification through additional germline testing. In the present study, 194 patients with advanced cancer who underwent tumor-only NGS between April 2015 and March 2018 were enrolled, and the incidences of possible and true SFs were evaluated. Among them, 120 patients (61.9%) harbored at least one possible SF. TP53 was the most frequent gene in which 97 variants were found in 91 patients (49.5%). Nine patients provided informed consent to undergo additional germline testing, and a total of 14 variants (BRCA1, n = 1; BRCA2, n = 2; PTEN, n = 2; RB1, n = 1; SMAD4, n = 1; STK11, n = 1; TP53, n = 6) were analyzed. Three variants (BRCA1, n = 1; BRCA2, n = 2) were confirmed to be SFs, whereas TP53 variants were confirmed to be somatic variants. To confirm the low prevalence of SFs in TP53, we analyzed 24 patients with TP53 variants who underwent a paired tumor-normal NGS assay. As expected, all TP53 variants were confirmed to be somatic variants. A total of 30 patients were tested for germline variants in TP53, but none of them resulted in true SFs, suggesting the low prevalence of SFs in this gene. Therefore, the significance of additional germline testing for TP53 variants appears to be relatively low in daily clinical practice using a tumor-only NGS assay, unless patients have any relevant medical or family history.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores Tumorais/genética , Variação Genética/genética , Proteína Supressora de Tumor p53/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA
15.
J Hum Genet ; 65(12): 1045-1053, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32661284

RESUMO

The management of secondary findings (SFs), which are beyond the intended purpose of the analysis, from clinical comprehensive genomic analysis using next generation sequencing (NGS) presents challenges. Policy statements regarding their clinical management have been announced in Japan and other countries. In Japan, however, the current status of and attitudes of clinical genetics professionals toward reporting them are unclear. We conducted a questionnaire survey of clinical genetics professionals at two time points (2013 and 2019) to determine the enforcement of the SF management policy in cases of comprehensive genetic analysis of intractable diseases and clinical cancer genome profiling testing. According to the survey findings, 40% and 70% of the respondents stated in the 2013 and 2019 surveys, respectively, that they had an SF policy in the field of intractable diseases, indicating that SF policy awareness in Japan has changed significantly in recent years. Furthermore, a total of 80% of respondents stated that their facility had established a policy for clinical cancer genome profiling testing in the 2019 survey. In both surveys, the policies included the selection criteria for genes to be disclosed and the procedure to return SFs, followed by recommendations and proposals regarding SFs in Japan and other countries. To create a better list of the genes to be disclosed, further examination is needed considering the characteristics of each analysis.


Assuntos
Genoma Humano/genética , Genômica/normas , Sequenciamento de Nucleotídeos em Larga Escala/normas , Neoplasias/genética , Revelação , Exoma/genética , Testes Genéticos , Humanos , Japão/epidemiologia , Neoplasias/epidemiologia , Neoplasias/patologia , Inquéritos e Questionários
16.
Biosci Biotechnol Biochem ; 84(3): 507-517, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31718466

RESUMO

Membrane-bound quinoprotein glucose dehydrogenase from acetic acid bacteria produces lactobionic acid by the oxidation of lactose. Its enzymatic activity on lactose and maltose is much lower than that on D-glucose. For that reason, the activity of the enzyme on disaccharides has been considered low. In this study, we show that the isomaltose-oxidizing activity of acetic acid bacteria is much higher than their lactose-oxidizing activity. In addition to isomaltose, the enzyme oxidized gentiobiose and melibiose to the same extent. According to the characteristics of the isomaltose-oxidizing activity and investigations using dehydrogenase-deficient mutant bacteria, we identified the responsible enzyme as membrane-bound quinoprotein glucose dehydrogenase.Abbreviations: AAB: acetic acid bacteria; m-GDH: membrane-bound quinoprotein glucose dehydrogenase; DCIP: 2,6-dichlorophenolindophenol; DP: degree of polymerization; HPAEC-PAD: high-performance anion-exchange chromatography with pulsed amperometric detection; NMR: nuclear magnetic resonance; TLC: thin layer chromatography; COSY: correlation spectroscopy.


Assuntos
Ácido Acético/metabolismo , Bactérias/metabolismo , Dissacarídeos/metabolismo , Glucose 1-Desidrogenase/metabolismo , Isomaltose/metabolismo , Melibiose/metabolismo , Oxirredução
17.
J Hum Genet ; 64(9): 945-954, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273322

RESUMO

Genome editing of the human embryo using CRISPR/Cas9 has the potential to prevent hereditary diseases from being transmitted to the next generation. However, attitudes to this technology have not been examined sufficiently among the genetic professionals who will use it in the near future. We conducted a questionnaire survey of Japanese clinical geneticists and certified genetic counselors. Differences were observed between them in their recognition of this technology and impressions on its difficulty and cost. Both groups worried about misuse of it, with insufficient information and rules. As key elements for such rules, they considered ethics, safety, and purpose. Most disapproved of modifying physical traits as an enhancement, though they hoped for the treatment of severe diseases. At current clinical sites, they tended to adopt a prudent attitude by mentioning only the possibility of genome editing in the future. Academic policies and legislation are required, especially for application in human embryos, through a consensus of professionals and general citizens. Furthermore, professionals should maintain awareness of new developments and regularly reexamine attitudes for the ongoing development of more suitable rules, education systems, and clinical protocols. As preparation for changes, opportunities to address ethical issues and initiate discussions are also required.


Assuntos
Atitude Frente a Saúde , Edição de Genes , Aconselhamento Genético , Conhecimento , Inquéritos e Questionários , Feminino , Humanos , Japão , Masculino
18.
Biosci Biotechnol Biochem ; 83(6): 1171-1179, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30777491

RESUMO

Acetic acid bacteria are used in the commercial production of lactobionic acid (LacA). However, the lactose-oxidizing enzyme of these bacteria remains unidentified. Lactose-oxidizing activity has been detected in bacterial membrane fractions and is strongly inhibited by d-glucose, suggesting that the enzyme was a membrane-bound quinoprotein glucose dehydrogenase, but these dehydrogenases have been reported to be incapable of oxidizing lactose. Thus, we generated m-GDH-overexpressing and -deficient strains of Komagataeibacter medellinensis NBRC3288 and investigated their lactose-oxidizing activities. Whereas the overexpressing variants produced ~2-5-fold higher amounts of LacA than the wild-type strains, the deficient variant produced no LacA or d-gluconic acid. Our results indicate that the lactose-oxidizing enzyme from acetic acid bacteria is membrane-bound quinoprotein glucose dehydrogenase. Abbreviations: LacA: lactobionic acid; AAB: acetic acid bacterium; m-GDH: membrane-bound quinoprotein glucose dehydrogenase; DCIP: 2,6-dichlorophenolindophenol; HPAEC-PAD: high-performance anion-exchange chromatography with pulsed amperometric detection.


Assuntos
Acetobacteraceae/enzimologia , Dissacarídeos/metabolismo , Glucose Desidrogenase/metabolismo , Membrana Celular/enzimologia , Glucose/metabolismo , Lactose/metabolismo , Oxirredução , Especificidade por Substrato
19.
Biosci Biotechnol Biochem ; 79(10): 1712-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25965080

RESUMO

Lactobionic acid was produced by acetic acid bacteria to oxidize lactose. Gluconobacter spp. and Gluconacetobacter spp. showed higher lactose-oxidizing activities than Acetobacter spp. Gluconobacter frateurii NBRC3285 produced the highest amount of lactobionic acid per cell, among the strains tested. This bacterium assimilated neither lactose nor lactobionic acid. At high lactose concentration (30%), resting cells of the bacterium showed sufficient oxidizing activity for efficient production of lactobionic acid. These properties may contribute to industrial production of lactobionic acid by the bacterium. The bacterium showed higher oxidizing activity on cellobiose than that on lactose and produced cellobionic acid.


Assuntos
Celobiose/metabolismo , Dissacarídeos/biossíntese , Gluconobacter/metabolismo , Lactose/metabolismo , Ácido Acético/metabolismo , Acetobacter/metabolismo , Fermentação , Oxirredução , Especificidade por Substrato
20.
BMC Med Ethics ; 14: 47, 2013 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-24267590

RESUMO

BACKGROUND: In studies publishing identifying personal information, obtaining consent is regarded as necessary, as it is impossible to ensure complete anonymity. However, current journal practices around specific points to consider when obtaining consent, the contents of consent forms and how consent forms are managed have not yet been fully examined. This study was conducted to identify potential issues surrounding consent to publish identifying personal information. METHODS: Content analysis was carried out on instructions for authors and consent forms developed by academic journals in four fields (as classified by Journal Citation Reports): medicine general and internal, genetics and heredity, pediatrics, and psychiatry. An online questionnaire survey of editors working for journals that require the submission of consent forms was also conducted. RESULTS: Instructions for authors were reviewed for 491 academic journals (132 for medicine general and internal, 147 for genetics and heredity, 100 for pediatrics, and 112 for psychiatry). Approximately 40% (203: 74 for medicine general and internal, 31 for genetics and heredity, 58 for pediatrics, and 40 for psychiatry) stated that subject consent was necessary. The submission of consent forms was required by 30% (154) of the journals studied, and 10% (50) provided their own consent forms for authors to use. Two journals mentioned that the possible effects of publication on subjects should be considered. Many journal consent forms mentioned the difficulties in ensuring complete anonymity of subjects, but few addressed the study objective, the subjects' right to refuse consent and the withdrawal of consent. The main reason for requiring the submission of consent forms was to confirm that consent had been obtained. CONCLUSION: Approximately 40% of journals required subject consent to be obtained. However, differences were observed depending on the fields. Specific considerations were not always documented. There is a need to address issues around the study objective, subjects' right to refuse consent and the withdrawal of consent. Whether responsibility for ensuring that the consent form has been signed lies with publishers also needs to be discussed.


Assuntos
Confidencialidade , Termos de Consentimento , Políticas Editoriais , Consentimento Livre e Esclarecido , Publicações Periódicas como Assunto/ética , Termos de Consentimento/ética , Termos de Consentimento/normas , Genética , Humanos , Consentimento Livre e Esclarecido/ética , Consentimento Livre e Esclarecido/normas , Consentimento Livre e Esclarecido/estatística & dados numéricos , Medicina Interna , Pediatria , Publicações Periódicas como Assunto/normas , Psiquiatria , Inquéritos e Questionários
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