Plasmodium falciparum associated placental pathology: a light and electron microscopic and immunohistologic study

Pathological changes were studied by light and electron microscopy on term placentas collected in Malawi from 20 P. falciparum infected women (11 primiparas and 9 multiparas). One placenta from an uninfected term primipara and 4 from multiparas were studied as controls. Changes included the presence of parasitized erythrocytes and malarial pigment particles in the intervillous space, excessive syncytial knotting, chronic basal villitis, malarial pigment deposits in the trophoblasts, trophoblastic damage with focal necrosis, partial loss of microvilli, and thickening of the trophoblastic basement membrane. Infected erythrocytes were not seen in the fetal circulation. Severity appeared to correlate with the level of maternal and placental parasitemias, regardless of infant birth weight or placental weight. Differences in the severity of pathological changes between primiparas and multiparas could not be demonstrated. Immunohistochemistry revealed that 45% of the placentas stained strongly for IgG and 15% stained for C3 and for P. falciparum antigens in the trophoblastic cytoplasm and basement membrane.     

Cystic dilatation of peribiliary glands in livers with adult polycystic disease and livers with solitary nonparasitic cysts: an autopsy study.

Cystic dilatation of peribiliary glands of intrahepatic and extrahepatic bile ducts was investigated in autopsied livers with adult polycystic disease (n = 8), in autopsied livers with solitary nonparasitic cysts (n = 18) and in normal autopsied livers (n = 23). In normal livers, cystic dilatation of intrahepatic peribiliary glands was absent or slight, when present. In livers with solitary nonparasitic cysts, cystic dilatation of intrahepatic peribiliary glands was present in varying degrees. In livers with adult polycystic disease, intrahepatic peribiliary glands showed frequent and severe cystic dilatation so marked that it was grossly recognizable. In contrast, peribiliary glands of the extrahepatic bile ducts showed no cystic dilatation in most cases, regardless of the three conditions examined. Liver parenchymal cysts were numerous in livers with adult polycystic disease, few in livers with solitary nonparasitic cysts and nonexistent in normal livers. Von Meyenburg complexes were present in 87.5% of livers with adult polycystic disease, in 16.7% of livers with solitary nonparasitic cysts and in 4.3% of normal livers. These findings suggest that intrahepatic peribiliary glands undergo cystic dilatation in livers with adult polycystic disease-and, to a lesser degree and frequency in livers with solitary nonparasitic cysts, probably because of congenital or genetic factors-and that these cystic changes may comprise a part of numerous cysts of adult polycystic disease.     

A potential peptide vaccine against two different strains of influenza virus isolated at intervals of about 10 years.

We have developed a strategy for making synthetic peptide vaccines, in which a peptide, HA127-133, derived from the hemagglutinin (HA) of A/Aichi/2/68(H3N2) influenza virus (Aichi/68) is introduced into the Ab binding component consisting of 43-46 and 54-58 residues of a pigeon cytochrome c analogue peptide, 46F50V54A. Indeed, this hybrid peptide, 46F/HA127-133/54A, induced impressive T-cell responses and antibody production neutralizing infectivity of Aichi/68 in vitro. In a subsequent study we found that 46F/HA127-133/54A(18mer) peptide antigen, which had been prepared by substitution at the central five residues of 46F50V54A with HA127-133, generated T-cell responses and neutralizing antibody responses as well. On the basis of these prior findings, in the present study we analyzed immunopotency of 46F/HA127-133/54A(18mer) in vivo administered in several ways to I-Ab mice. We show herein that this peptide vaccine loaded in multilamellar liposomes without adjuvant protects the mice against infection with Aichi/68 within 2 weeks after final immunization. Further, this peptide vaccine was shown to be effective in preventing infection with a naturally occurring antigenic variant, A/Texas/1/77(H3N2), carrying the same sequence at 127-133 of the HA as Aichi/68 virus. Since this part of the HA is relatively conserved among H3 subtype influenza viruses, our peptide vaccine may become the basis for a new strategy to prepare effective vaccines that will overcome the ineffectiveness of classical vaccines attributable to antigenic drift of influenza viruses.     

Factors responsible for pathogenicity in chickens of a low-pathogenic H7N7 avian influenza virus isolated from a feral duck

Highly pathogenic avian influenza viruses have poly-basic amino acid sequences at the cleavage site in their hemagglutinin (HA). Although this poly-basic region is a prerequisite factor for pathogenicity in chickens, not much is known about additional factors responsible for the acquisition of pathogenicity of the duck influenza virus in chickens. Here, we introduced multiple basic amino acid residues into the HA cleavage site of the A/duck/Hokkaido/Vac-2/2004 (H7N7) strain of avian influenza virus, which has low pathogenicity in chickens; the resultant Vac2sub-P0 strain was not intravenously pathogenic in chickens. In contrast, the Vac2sub-P3 strain, which was recovered from three consecutive passages of Vac2sub-P0 in chicks, was intravenously pathogenic in chickens. Six amino acid substitutions were identified by comparison of the Vac2sub-P3 and Vac2sub-P0 genomic sequences: Lys123Glu in PB2, Asn16Asp in PB1, Glu227Gly and Ile388Thr in HA, Gly228Arg in M1, and Leu46Pro in M2. The results of intravenous inoculations of chickens with recombinant virus indicated that all six amino acid substitutions were required to varying degrees for Vac2sub-P3 pathogenicity, with Glu227Gly and Ile388Thr in HA being particularly essential. These results reveal the roles of additional viral factors in the acquisition of pathogenicity in addition to the previously characterized role of the poly-basic amino acid sequences at the HA cleavage site.     

The genetic and antigenic diversity of avian influenza viruses isolated from domestic ducks, muscovy ducks, and chickens in northern and southern Vietnam, 2010–2012

To estimate the prevalence of avian influenza virus infection in Vietnam, surveillance was conducted in domestic and wild birds from households, live-bird markets, slaughtering sites, and bird sanctuaries in Vietnam between October 2010 and October 2012. Of the 4,550 samples collected, 226 influenza A virus isolates were obtained from domestic ducks, muscovy ducks, and chickens. Of these, 25 and 22 H5N1 highly pathogenic avian influenza viruses (HPAIVs) were isolated from apparently healthy domestic ducks in live-bird markets and slaughtering sites in northern and southern Vietnam, respectively. The HA genes of H5 viruses isolated from birds in northern Vietnam phylogenetically belonged to the genetic clade 2.3.2.1 and those in southern Vietnam belonged to the genetic clade 1.1. In addition, 39 H3, 12 H4, 1 H5, 93 H6, 2 H7, 18 H9, 3 H10, and 11 H11 viruses were isolated. Phylogenetic and antigenic analyses of the H6 and H9 viruses revealed that they were closely related to the isolates obtained from domestic poultry in China. Phylogenetic analyses of internal gene segments of these isolates revealed that these viruses were circulating in both domestic and wild birds in Asia and reassortment events had occurred frequently. Therefore, it will be important to continue the surveillance and strict controls over the movement and trade of poultry and poultry products in order to eradicate H5N1 HPAIV from Asia.     

Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation

The FMS-related tyrosine kinase 3 (FLT3) internal tandem duplication mutations (FLT3-ITD) positive acute myeloid leukemia (AML) is a disease with a dismal outcome. Gilteritinib is a second-generation FLT3 inhibitor with activity against ITD and high affinity toward the FLT3 receptor, thereby showing therapeutic potential for relapsed/refractory FLT3-mutated AML. Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) identical sibling donor was performed in a 38-year-old Japanese male with FLT3-ITD positive AML. Neutrophil engraftment (>0.5 × 10⁹/L) was achieved on day 16, and bone marrow remission was revealed on day 32. The patient's AML relapsed hematologically four months after BMT and was resistant to salvage chemotherapy. Gilteritinib was administered and the patient achieved non-remission but ‘stable disease’ status according to the response criteria. During administration, liver damage was observed but controllable. The patient received cord blood transplantation (CBT) as the second hematopoietic stem cell transplantation (HSCT) three months after relapse and achieved second remission. There was no evidence of recurrence of AML four months after CBT. This case demonstrates that gilteritinib can control FLT3-ITD positive AML that relapsed early after initial HSCT and can bridge to second HSCT.     

Clinical outcome of endoscopic aspiration mucosectomy for early stage gastric cancer

BACKGROUND: Endoscopic mucosal resection is an established treatment option for early stage gastric cancer. However, several problems with endoscopic mucosal resection remain to be solved, such as appropriate treatment for recurrence and incomplete tumor resection. The outcome for patients undergoing endoscopic aspiration mucosectomy (endoscopic mucosal resection) by a modification of the cap-fitted technique was evaluated retrospectively to determine factors associated with complete resection and tumor recurrence. METHODS: Endoscopic mucosal resection was performed in 106 patients with early stage gastric cancers up to 20 mm in diameter that were well or moderately differentiated adenocarcinoma. All were superficial lesions without ulceration, distinct signs of submucosal invasion, or a poorly demarcated border. En bloc (tumors <10 mm in diameter) or piecemeal (tumors 10-20 mm in diameter) resection was performed. Follow-up endoscopy was performed at 2, 6, 12, 18, and 24 months and thereafter once per year. Outcome and factors associated with complete resection and tumor recurrence were assessed retrospectively. RESULTS: Sixty-eight patients (64%) underwent en bloc resection and 38 (36%) piecemeal resection. The mean longest dimension (SD) of the resected lesions was significantly greater after piecemeal resection (12.3 [4.0] mm) than after en bloc resection (7.6 [4.0] mm; p < 0.01). In patients with tumors completely resected, there was no recurrence after either en bloc or piecemeal resection. Six of 8 patients found to have submucosal invasion after endoscopic mucosal resection underwent surgery. Patients with incompletely resected intramucosal lesions underwent additional endoscopic treatment. Cancer recurred in 3 patients (2.8%), all of whom had lesions measuring more than 15 mm in diameter. CONCLUSIONS: Endoscopic mucosal resection is safe and useful for the management of early stage gastric cancer. Further improvement in outcome requires more accurate preoperative diagnosis and postoperative histopathologic evaluation. Patients with incompletely resected lesions should undergo aggressive additional treatment.     

Analysis of BRCAness with multiplex ligation-dependent probe amplification using formalin-fixed and paraffin-embedded pancreatic ductal adenocarcinoma tissue obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy

Background/Objectives

A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness has been receiving attention as a novel predictor of anticancer drug sensitivity in PDAC, making the screening of BRCAness paramount.