Right pleural effusion in Fitz-Hugh-Curtis syndrome

Right pleural effusion was diagnosed in a 36-year-old woman with right upper quadrant pain and fever. Enhanced pelvic computed tomography performed because of irregular genital bleeding revealed the pelvic inflammatory disease. Upon further questioning, the patient confirmed that she had recently undergone therapy for Chlamydia trachomatis infection. Therefore she was given an injection of tetracycline because we suspected Fitz-Hugh-Curtis syndrome (FHCS), a pelvic inflammatory disease characterized by perihepatitis associated with chlamydial infection. A remarkable clinical response to antibiotics was noted. The right upper quadrant pain was due to perihepatitis, and the final diagnosis was FHCS. Right pleural effusion may be caused by inflammation of the diaphragm associated with perihepatitis. Once chlamydial infection reaches the subphrenic liver, conditions in the closed space between the liver and diaphragm due to inflammatory adhesion may be conductive to chlamydial proliferation. The possibility of FHCS should be considered in patients and carefully distinguished from other abdominal diseases.     

Emergence of multidrug-resistant Corynebacterium striatum as a nosocomial pathogen in long-term hospitalized patients with underlying diseases

During a 53-month period (March 1994 to August 1998), 48 Corynebacterium striatum isolates recovered from clinical specimens were characterized. The organisms were identified by both phenotypic characteristics and 16S rRNA gene sequence analysis. Thirty-six (75%) were isolated from sputum/bronchial aspirates, 10 (21%) from wound exudates/pus, 1 (2%) from vaginal discharge, and 1 (2%) from an otorrheic specimen. All 48 patients had been hospitalized for treatment of an underlying disease and had received antibiotics previously. The C. striatum isolates were considered pathogenic based on their abundance within polymorphonuclear neutrophils and their dominant growth in culture. Sensitivities of isolates to 11 antibiotics were determined by broth microdilution. MIC90 values of the isolates were 1 microg/mL for vancomycin, 16 microg/mL for penicillin and ampicillin, 32 microg/mL for minocycline, and > or = 32 microg/mL for cephalosporins, imipenem, ofloxacin, and macrolides. Restriction fragment-length polymorphism analysis with pulsed-field gel electrophoresis was used to determine the clonal identity. The pulse-field gel electrophoresis profiles revealed 14 distinct patterns with 20 subtypes. The isolates for the nosocomial outbreaks of C. striatum included 3 types (A, D, and E) with 4 subtypes (A1, A2, D2, and E). All 4 genotypes had broad-spectrum resistance to antimicrobial agents. Furthermore, type E strain isolated from 3 patients in the same ward was sensitive only to vancomycin. We conclude that C. striatum should be considered an emerging multidrug-resistant nosocomial pathogen in patients hospitalized for a prolonged period and/or in immunocompromised patients with such underlying conditions as cerebrovascular disease, pulmonary disease, diabetes, or malignancy.     

Tributyltin-induced endoplasmic reticulum stress and its Ca-mediated mechanism

Organotin compounds, especially tributyltin chloride (TBT), have been widely used in antifouling paints for marine vessels, but exhibit various toxicities in mammals. The endoplasmic reticulum (ER) is a multifunctional organelle that controls post-translational modification and intracellular Ca^2 + signaling. When the capacity of the quality control system of ER is exceeded under stress including ER Ca^2 + homeostasis disruption, ER functions are impaired and unfolded proteins are accumulated in ER lumen, which is called ER stress. Here, we examined whether TBT causes ER stress in human neuroblastoma SH-SY5Y cells. We found that 700 nM TBT induced ER stress markers such as CHOP, GRP78, spliced XBP1 mRNA and phosphorylated eIF2α. TBT also decreased the cell viability both concentration- and time-dependently. Dibutyltin and monobutyltin did not induce ER stress markers. We hypothesized that TBT induces ER stress via Ca^2 + depletion, and to test this idea, we examined the effect of TBT on intracellular Ca^2 + concentration using fura-2 AM, a Ca^2 + fluorescent probe. TBT increased intracellular Ca^2 + concentration in a TBT-concentration-dependent manner, and Ca^2 + increase in 700 nM TBT was mainly blocked by 50 μM dantrolene, a ryanodine receptor antagonist (about 70% inhibition). Dantrolene also partially but significantly inhibited TBT-induced GRP78 expression and cell death. These results suggest that TBT increases intracellular Ca^2 + concentration by releasing Ca^2 + from ER, thereby causing ER stress.     

Anti‐tumor effects of suberoylanilide hydroxamic acid on Epstein–Barr virus‐associated T cell and natural killer cell lymphoma

The ubiquitous Epstein–Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells and is associated with various lymphoid malignancies. Recent studies have reported that histone deacetylase (HDAC) inhibitors exert anticancer effects against various tumor cells. In the present study, we have evaluated both the in vitro and in vivo effects of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on EBV‐positive and EBV‐negative T and NK lymphoma cells. Several EBV‐positive and EBV‐negative T and NK cell lines were treated with various concentrations of SAHA. SAHA suppressed the proliferation of T and NK cell lines, although no significant difference was observed between EBV‐positive and EBV‐negative cell lines. SAHA induced apoptosis and/or cell cycle arrest in several T and NK cell lines. In addition, SAHA increased the expression of EBV‐lytic genes and decreased the expression of EBV‐latent genes. Next, EBV‐positive NK cell lymphoma cells were subcutaneously inoculated into severely immunodeficient NOD/Shi‐scid/IL‐2Rγnull mice, and then SAHA was administered intraperitoneally. SAHA inhibited tumor progression and metastasis in the murine xenograft model. SAHA displayed a marked suppressive effect against EBV‐associated T and NK cell lymphomas through either induction of apoptosis or cell cycle arrest, and may represent an alternative treatment option.     

Acute aggravation of subdural fluid collection associated with dural metastasis of malignant neoplasms: case report and review of the literature

A 63-year-old woman was admitted to our hospital with serious headache and vomiting. Five months before admission, she had undergone surgery for a primary advanced gastric cancer. Neuroradiological examinations revealed subdural fluid collection. We twice performed evacuation of the subdural fluid collection. However, aggravation of her state of consciousness progressed and she passed away. Histological examinations demonstrated that the dural veins were infiltrated by numerous tumor cells that produced mucus; however, ruptured vessels were not found. Furthermore, the subdural fluid collection increased shortly after the initial operation. We infer that the cause of the collection, which was associated with the dural metastasis of malignant tumors, was not only mucin secretion by tumor cells but also a rapid increase in perfusion pressure in the vessels of the dura mater, resulting in extravasation of plasma components into the subdural space. Our case demonstrates that the pathogenetic mechanism that is specific for subdural fluid collection caused by dural metastasis of malignant tumors differs from the mechanism of production of subdural hematoma associated with dural metastasis.     

Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium

Cell adhesion molecule 1 (CADM1), formerly referred to as SgIGSF, TSLC1, or Necl-2, has been characterized as a mast-cell adhesion molecule that mediates efficient interactions with mesothelial cells. Here, we examined whether CADM1 might be involved in the diffuse tumor growth over the pleural surface that characterizes malignant pleural mesothelioma (MPM). Immunohistochemical and western blot analyses revealed that 14 (25%) of 57 MPMs expressed the full-length form of CADM1 on the cell membrane, but non-neoplastic mesothelial cells did not express it at all. The majority of available MPM cell lines also expressed the full-length form of CADM1. We compared CADM1-positive and -negative MPM cells in culture within soft agar and in coculture on mesothelial or fibroblastic monolayers. Within soft agar, CADM1-negative MPM cells were capable of forming colonies, whereas CADM1-positive cells were not, suggesting that CADM1 is a potential tumor suppressor of MPM, consistent with the past characterization of this molecule in other types of tumors. However, in coculture on mesothelial cell monolayers lacking full-length CADM1, CADM1-positive MPM cells spread more widely and grew more quickly, whereas the CADM1-negative cells piled up. Transfection of the CADM1-negative cells with CADM1 cDNA caused them to behave like the CADM1-positive cells, with faster, more widespread growth. These phenotypic differences were not detectable in cocultures on lung fibroblastic monolayers, in which all MPM cells grew much more slowly than on mesothelial cells, irrespective of CADM1 positivity. CADM1 thus appears to mediate efficient adhesion and growth of MPM cells specifically on mesothelial cells, probably via trans-heterophilic binding, and thus may be involved in the manifestation of a considerable subset of MPMs as diffusely growing tumors disseminated over the pleural surface.