Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

The use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two different Streptococcus pneumoniae serotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotype in vitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells

奈良における侵襲性GBS感染症における臨床的特徴と分子疫学的特徴(2007～2016年)

Invasive Streptococcus agalactiae (GBS) infections are increasingly common among neonates and the elderly. Therefore, GBS surveillance for better antibiotic treatment and prophylaxis strategies are needed. We retrospectively evaluated the clinical aspects of invasive infections and the phenotypic and genetic diversity of infectious isolates from Nara, Japan, collected between 2007 and 2016, by using information from hospital records. GBS strains collected from the blood and cerebrospinal fluid cultures were evaluated for capsular types, multi-locus sequence typing (MLST), antibiotic susceptibility, antibiotics resistance gene, and pulsed-field gel electrophoresis. Forty GBS isolates (10 from children and 30 from adults) were analyzed, and the distribution of molecular serotype and allelic profiles varied between children and adults. We found the rates of early-onset disease in neonates with birth complications to be higher than that of previous reports, indicating that there could be relevance between complications at birth and early-onset disease. Standard antibiotic prophylaxis strategies may need to be reconsidered in patients with birth complications. In adults, the mean age of the patients was 68 years (male: 63%). Primary bacteremia was the most common source of infection. In the neonates, six had early-onset diseases and four had late-onset diseases. The most frequently identified strains were molecular serotype Ia ST23 (40%) and molecular serotype Ib ST10 (20%) in children and molecular serotype Ib ST10 (17%), molecular serotype VI ST1 (13%), and molecular serotype V ST1 (13%) in adults. Levofloxacin-resistant molecular serotype Ib strains and molecular serotypes V and VI ST1 were common causes of GBS infection in adults but were rarely found in children. Furthermore, pulsed-field gel electrophoresis in our study showed that specific clone isolates, that tend to have antibiotics resistance were widespread horizontally for a decade. Continuous surveillance and molecular investigation are warranted to identify the transmission route and improve antibiotic treatment strategies.博士（医学）・甲第773号・令和3年3月15日Copyright: © 2020 Hirai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A case of pulmonary tuberculosis accompanied with immune thrombocytopenic purpura

AbstractA 30-year-old Japanese woman with chest pain and nodules in the left upper lung field was diagnosed as having pulmonary tuberculosis by sputum examination. Purpura on her legs had lasted for 3 months and her platelet count was 1.9 × 104/mm3 on admission. She was also diagnosed as having immune thrombocytopenic purpura because of elevation of serum PA-IgG and proliferation of megakaryocytes in the bone marrow. Anti-tubercular therapy and steroid therapy were concurrently performed, resulted in recovery of the platelet count. Steroid therapy was gradually tapered off and then withdrawn, thereafter anti-tubercular therapy was finished. She has been relapse-free.Cases of pulmonary tuberculosis accompanied with immune thrombocytopenic purpura are rare. The pathogenesis in the present case was suggested to have occurred through an immunological mechanism

Resected Intrahepatic Cholangiocarcinoma with Anaphylactic Shock from a Preoperative Liver Function Test before Hepatectomy

The indocyanine green test is a reliable liver function examination before major hepatectomy, and anaphylaxis is rarely a concern. A 65-year-old male patient without epigastralgia was diagnosed with a 2.2-cm intrahepatic cholangiocarcinoma. He had no history of allergic reactions. Some liver dysfunction was indicated by the laboratory data; however, there was no marked obstructive jaundice and the liver functional reserve was maintained by technetium-99m galactosyl serum albumin. The indocyanine green test was routinely performed, but the patient immediately demonstrated severe anaphylaxis due to indocyanine green administration. He had cardiorespiratory arrest, but recovered after immediate resuscitation. Although acute renal and respiratory failure was significant, the patient recovered at day 10 after the event, and his liver function and other organ functions were improved. Then, the scheduled left hepatectomy with caudate and extrahepatic duct resection was successfully performed without issues. The patient exhibited no allergic response against the administration of antibiotics or other drugs and the postoperative course was uneventful. The patient was discharged on day 17. The tumor was diagnosed as stage III intrahepatic cholangiocarcinoma and R0 resection was accomplished. Preoperative management, including the liver functional loading test, should be carefully carried out before major hepatectomy

Sonazoid-enhanced intraoperative ultrasonography in patients with gall bladder diseases: A preliminary study

Background:Ultrasonography using Sonazoid, a novel contrast agent containing microbubbles, is a useful diagnostic modality for intrahepatic mass lesions with specific characteristics in two phases: contrast enhancement of early vascular perfusion and perfusion defect of the lesion in the late phase. To improve the diagnostic accuracy of intraoperative ultrasonography (IOUS) in biliary neoplasms, particularly gall bladder, we investigated the usefulness of the Sonazoid contrast agent in a preliminary study.Subjects and Methods:We examined IOUS images of 23 patients with gall bladder disease. Sonazoid was administered intravenously, and early arterial and venous phase images of the tumor were obtained during laparotomy.Results:Tumors included the localized type of adenomyomatosis in the fundus of the gallbladder (GAM) in seven patients as benign controls, adenomatous diseases in three, and gallbladder carcinoma (GC) in 13. Sonazoid IOUS scanning was performed in all patients, with no adverse effects. Although GC showed high enhancement in 77% of the tumors, GAM and adenoma also showed mild enhancement in more than half of them. Pseudo-positivity was observed in one case of hyperplastic polyps, and pseudo-negativity was observed in two patients. Cholesterol polyps and a suspicious lesion of liver metastasis by the computed tomography were not enhanced with Sonazoid treatment.Conclusion:Although there remains a problem of pseud-positivity in the intracystic lesions, Sonazoid IOUS may be a useful tool to detect vascularity and its location or extension of gallbladder diseases; however, neither significance of differential diagnosis with benign diseases nor other clinical significance was found

Characterization of Gene Use and Efficacy of Mouse Monoclonal Antibodies to Streptococcus pneumoniae Serotype 8 ▿ †

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia in the United States and globally. Despite the availability of pneumococcal capsular polysaccharide (PPS) and protein conjugate-based vaccines, the prevalence of antibiotic-resistant pneumococcal strains, serotype (ST) replacement in nonconjugate vaccine strains, and uncertainty as to whether the PPS vaccine that is used in adults protects against pneumonia emphasize the need for continued efforts to understand the nature of protective PPS antibody responses. In this study, we generated mouse monoclonal antibodies (MAbs) to a conjugate consisting of the PPS of serotype 8 (PPS8) S. pneumoniae and tetanus toxoid. Thirteen MAbs, including four IgMs that bound to PPS8 and phosphorylcholine (PC) and five IgMs and four IgG1s that bound to PPS8 but not PC, were produced, and their nucleotide sequences, epitope and fine specificity, and efficacy against lethal challenge with ST8 S. pneumoniae were determined. MAbs that bound to PPS8 exhibited gene use that was distinct from that exhibited by MAbs that bound to PC. Only PPS8-binding MAbs that did not bind PC were protective in mice. All 13 MAbs used germ line variable-region heavy (VH) and light (VL) chain genes, with no evidence of somatic hypermutation. Our data reveal a relationship between PPS specificity and VH gene use and MAb efficacy in mice. These findings provide insight into the relationship between antibody molecular structure and function and hold promise for the development of novel surrogates for pneumococcal vaccine efficacy

Risk factors for hepatic insufficiency after major hepatectomy in non-cirrhotic patients

Summary: Background: Although recent advances in surgical techniques and perioperative management have reduced the morbidity and mortality after hepatectomy, hepatic insufficiency after major hepatectomy remains an important concern. This study aimed to clarify the risk factors for post-hepatectomy liver insufficiency. Methods: We enrolled 103 consecutive patients who underwent major hepatectomy which was defined as resection of four or more segments. Hepatic insufficiency is defined as an increase in serum total bilirubin after hepatectomy of 7 mg/dL or more, or death from multiple organ failure. We compared the patient disposition, demographics, perioperative factors such as surgical method, combined procedure, morbidity and so on between the patients with or without hepatic insufficiency. Results: Hepatic insufficiency occurred in 14 patients (14%) and six of them died during the hospital stay (6%). Risk factors by univariate analysis were the percentage of hepatic parenchyma to be resected (P = .025), combined procedure (P = .008) and postoperative morbidity excluding hepatic insufficiency (P < .001). A combined procedure (P = .036) and postoperative morbidity excluding hepatic insufficiency (P = .002) were a significant risk factor by multivariate analysis. Conclusion: Unless remaining liver after hepatectomy has enough volume, combined procedure may account for hepatic insufficiency, which can follow the development of postoperative morbidity. Keywords: Risk factor, Hepatic insufficiency, Major hepatectom