Low-Specificity and High-Sensitivity Immunostaining for Demonstrating Pathogens in Formalin-Fixed, Paraffin-Embedded Sections

The present review describes a part of the author’s own experience in applying immunoperoxidase staining to routine histopathological diagnosis. The target disorder was focused on infection. In the practice of pathology diagnosis services, it is important for us diagnostic pathologists to judge whether the lesion is caused by an infection or not. When an infectious disease is highly likely, the visualization of pathogens within the inflammatory lesion is required to suggest a causative agent. Two main approaches the author would like to introduce include (1) the use of commercially available antisera showing wide cross-reactivity to a variety of bacteria and (2) the use of diluted patients’ sera. These immunohistochemical studies employing “low-specificity” and “high-sensitivity” probes are useful for confirming the localization of pathogen within the infectious lesion

Pathology of Gangrene

Pathological features of gangrene are described. Gangrene is commonly caused by infection of anaerobic bacteria. Dry gangrene belongs to noninfectious gangrene. The hypoxic/ischemic condition accelerates the growth of anaerobic bacteria and extensive necrosis of the involved tissue. Clostridial and non-clostridial gangrene provokes gas formation in the necrotic tissue. Acute gangrenous inflammation happens in a variety of tissues and organs, including the vermiform appendix, gallbladder, bile duct, lung, and eyeball. Emphysematous (gas-forming) infection such as emphysematous pyelonephritis may be provoked by Escherichia coli and Klebsiella pneumoniae. Rapidly progressive gangrene of the extremities (so-called “flesh-eating bacteria” infection) is seen in fulminant streptococcal, Vibrio vulnificus, and Aeromonas hydrophila infections. Fournier gangrene is an aggressive and life-threatening gangrenous disease seen in the scrotum and rectum. Necrotizing fasciitis is a subacute form of gangrene of the extremities. Of note is the fact that clostridial and streptococcal infections in the internal organs may result in a lethal hypercytokinemic state without association of gangrene of the arms and legs. Uncontrolled diabetes mellitus may play an important role for vulnerability of the infectious diseases. Pseudomonas-induced malignant otitis externa and craniofacial mucormycosis are special forms of the lethal gangrenous disorder

Cytological Diagnosis of Infectious Diseases: Identification of Pathogens and Recognition of Cellular Reactions

Cytological diagnosis of infectious diseases is as important as the cytodiagnosis of malignancies, because the detection of pathogens in cytological specimens is crucially valuable for prompt and appropriate patients’ treatment. When compared with histological diagnosis, cytology is strong at detecting microbes under Papanicolaou and Giemsa stains. Host response against the infectious agent can be estimated by the type of background inflammatory cells. Patterns of the inflammatory cellular responses against extracellular and intracellular pathogens should be recognized. Immunocytochemical and molecular approaches can be applied, even when we have only one cytology specimen in hand. The cell transfer technique is useful to create plural material from one glass slide for immunocytochemistry and other techniques. In case of transmissible disorders including sexually transmitted diseases, the prompt and appropriate diagnosis will avoid avoidable transmission of infectious agents among people, and eventually contribute to the safety of the human society

The characteristics of myelomatous pleural effusion（MPE） as a rare complication：a case and review of the literature.

We reported a patient with multiple myeloma who developed myelomatous pleural effusion （MPE）. This patient had nine courses of chemotherapy, and pleural effusion developed after the fourth course. Although administration of several chemotherapeutic agents and intrapleural administration of OK432 were performed, the patient died 4 months after the development of MPE. We analyzed the previous reports to clarify the characteristics of patients who developed MPE

High-mass star formation in Orion triggered by cloud-cloud collision II, Two merging molecular clouds in NGC2024

We analyzed the NANTEN2 13CO (J=2-1 and 1-0) datasets in NGC 2024. We found that the cloud consists of two velocity components, whereas the cloud shows mostly single-peaked CO profiles. The two components are physically connected to the HII region as evidenced by their close correlation with the dark lanes and the emission nebulosity. The two components show complementary distribution with a displacement of 0.4 pc. Such complementary distribution is typical to colliding clouds discovered in regions of high-mass star formation. We hypothesize that cloud-cloud collision between the two components triggered the formation of the late O stars and early B stars localized within 0.3 pc of the cloud peak. The collision timescale is estimated to be ~ 10^5 yrs from a ratio of the displacement and the relative velocity 3-4 km s-1 corrected for probable projection. The high column density of the colliding cloud 1023 cm-2 is similar to those in the other massive star clusters in RCW 38, Westerlund 2, NGC 3603, and M42, which are likely formed under trigger by cloud-cloud collision. The present results provide an additional piece of evidence favorable to high-mass star formation by a major cloud-cloud collision in Orion.Comment: 24 pages, 10 figures, submitted for publication in PASJ (cloud-cloud collision special issue

HCV Virus and Lymphoid Neoplasms

Hepatitis C virus (HCV) is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab) positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis

The synergistic effects of omega-3 fatty acids against 5-fluorouracil-induced mucosal impairment in mice

Background: Anti-cancer pharmaceuticals frequently have adverse side effects on patients such as gastrointestinal involvement limiting their clinical applications. These effects may be controlled by nutritional interventions, however, there are few studies that have shown any mechanistic effects. In this study, we examined effects of diet enhanced with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on 5-fluorouracil (5-FU)-induced intestinal impairment and immunity in mice. Methods: C57Bl6 mice were randomized to control diet, control diet + EPA, control + DHA, control + fish oil, or diet enchanced with DHA/EPA. After seven days of each respective diet, mice, excluding those in the sham group, were treated with 10 mg/kg/day 5-FU for 7 days. The effects of 5-FU-induced impairment in the small intestine were assessed using cytokine concentrations in serum and tissue, secretory immunoglobulin (Ig) A, diamine oxidase (DAO) activity, the length of the small intestine, and the expression of apoptosis signaling genes. Results: The EPA/DHA-enhanced diet resulted in the most beneficial, synergystic and protective effect against 5-FU induced weight loss. Protection against inflammation, impaired intestinal function, and immunity of the small intestine were also observed. Individually, a DHA-enriched diet demonstrated a protective effect against 5-FU damage with longer small intestine mucosal and crypt lengths, greater DAO activity, and higher IgA concentrations, whereas the EPA-enriched diet resulted in decreased inflammatory cytokine concentrations in both plasma and small intestine and expression of apoptosis target genes. Conclusions: In conclusion, a diet enhanced with EPA and DHA results in synergism protecting against the detrimental effects of 5-FU and limiting chemotherapy induced mucosal impairment

Rituximab Administration and Reactivation of HBV

Rituximab is a drug used for the treatment of B-cell non-Hodgkin's lymphoma, and its range of use has expanded to the treatment of collagen diseases such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. One serious complication of rituximab use is the reactivation of dormant hepatitis B virus, and prevention of this phenomenon has become an urgent issue. This paper provides a general outline of the problem through an analysis of patient cases that we and other groups have experienced to date

Hyperocclusion up-regulates CCL3 expression in CCL2- and CCR2-deficient mice.

Excessive mechanical stress (MS) during hyperocclusion is known to result in disappearance of the alveolar hard line, enlargement of the periodontal ligament (PDL) space, and destruction of alveolar bone, leading to occlusal traumatism. We have recently reported that MS induces predominantly C-C chemokine ligand (CCL) 2 expression in PDL tissues, leading, via C-C chemokine receptor (CCR) 2, to MS-dependent osteoclastogenesis in alveolar bone. Thus, we hypothesize that ablation of the CCL2/CCR2 signaling pathway should suppress MS-induced osteoclastogenesis-associated chemokines and alleviate occlusal traumatism. We examined the effect of MS on chemokine expression and osteoclastogenesis using in vivo and in vitro hyperocclusion models with CCL2-deficient (CCL2((-/-))) and CCR2-deficient (CCR2((-/-))) mice. Compared with that in wild-type mice, expression of CCL3 in PDL cells and TRAP-positive cells in alveolar bone from CCL2((-/-)) and CCR2((-/-)) mice was up-regulated, even in the absence of MS. Furthermore, the expression of CCL3 and TRAP-positive cells was significantly increased after both 4 and 7 days of hyperocclusal MS loading in CCL2((-/-)) and CCR2((-/-)) mice. Hyperocclusion induced compensatory CCL3 expression and promoted osteoclastogenesis to counterbalance deficient CCL2/CCR2 signaling, suggesting that co-expression of CCL3 with CCL2 may precipitate synergistic, MS-dependent alveolar bone destruction during occlusal traumatism.Abbreviations: MS, mechanical stress; PDL, periodontal ligament; CCL2, CC chemokine ligand 2 (MCP-1; monocyte chemoattractant protein-1); CCR2, CC chemokine receptor 2; CCL3, CC chemokine ligand 3 (MIP-1α); CCL5, CC chemokine ligand 5 (RANTES).福岡歯科大学2013年