Plasma Epstein-Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma.

BACKGROUND: To test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at midcourse of chemoradiotherapy (CRT)/radiotherapy (RT), with respect to the plasma load of Epstein-Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: One hundred seven patients with stage IIB-IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before therapy (pre-DNA), at completion of 4 weeks of CRT/RT (mid-DNA), and within 3 months of completion of therapy (post-DNA). The end points are post-DNA load, a recognized surrogate of survival, and clinical outcome. RESULTS: Ninety-three percent of patients had detectable EBV DNA before therapy (median load = 972 copies/ml). EBV DNA became undetectable in 55 (51%) patients at the end of week 4 of therapy. Detectable mid-DNA was associated with worse clinical outcome (median follow-up time, 6.2 years), for distant failure [hazard ratio (HR) 12.02, 95% confidence interval (CI) 2.78-51.93; P < 0.0001], progression-free survival (PFS; HR 4.05, 95% CI 1.89-8.67, P < 0.0001), and overall survival (OS; HR 3.29, 95% CI 1.37-7.90, P = 0.0077). Seventy-four percent of all failures were associated with detectable mid-DNA, whereas 34% of all failures were associated with detectable post-DNA. Stratification by tumor stage (IIB, III, IV) has no significant prognostic effect. CONCLUSIONS: Unfavorable EBV DNA response at midcourse of RT/CRT is an adverse prognosticator for treatment outcome, is linked to majority of all failures, and discriminates outcome better than tumor stage. The data could provide a basis for trial design that addresses alteration of therapy intensity during the latter phase of CRT, and adjuvant therapy. Validation studies are awaited.

Adult T-cell leukaemia/lymphoma can mimic other lymphomas in a non-endemic area: dilemmas in diagnosis and treatment.

BACKGROUND: The diagnosis of Adult T-cell leukaemia/lymphoma (ATL) in non-endemic regions is challenging. AIM: This study analyses the clinicopathologic features and diagnostic processes of ATL patients in Taiwan. METHODS: ATL patients diagnosed and treated at Taipei Veterans General Hospital from 1998 through 2010 were retrospectively identified. The diagnosis of ATL was confirmed by in situ detection of human T-cell leukaemia virus type 1 (HTLV-1) when necessary. Patients' data were reviewed and analysed. RESULTS: Fourteen ATL patients were identified, among whom six (42.9%) had an antecedent diagnosis of other malignant lymphomas before the ATL diagnosis, including two diagnosed with Hodgkin disease (HD), one with peripheral T-cell lymphoma, two with chronic lymphocytic leukaemia and one with angioimmunoblastic T-cell lymphoma. Of the 14 patients, eight (57%) were subclassified as the acute type, three (21.4%) as the lymphoma type, and three (21.4%) as the chronic type ATL. Five of six (83.3%) patients with initial non-ATL misdiagnosis were diagnosed with non-acute type ATL. In particular, a patient with an antecedent diagnosis of HD presented with typical Reed-Sternberg (RS)-like cells harbouring Epstein-Barr virus genomes in affected lymph nodes. The patient progressed to acute type ATL 3 years after the initial diagnosis, and HTLV-1 genomes were identified in the previous RS-like cells. CONCLUSION: In non-endemic areas, such as Taiwan, ATL, particularly the non-acute type, may mimic other lymphomas and easily be misdiagnosed. HTLV-1 serology should be routinely screened in all malignant lymphoma patients. In situ detection of HTLV-1 is helpful in cases with diagnostic dilemmas.

Reappraisal of the importance of mutations in the NS5A-PKR-binding domain of hepatitis C-1b virus in the era of optimally individualized therapy.

Past studies have reported that mutations in the protein kinase R-binding domain (PKRBD) sequences of hepatitis C virus (HCV) NS5A proteins are correlated with response to fixed-duration interferon (IFN)-based therapy in patients infected with HCV-1b. In this study, we investigated whether the substitutions in PKRBD, including the IFN sensitivity-determining region (ISDR) and 26 additional downstream amino acids from ISDR, will have effects upon patients infected with chronic HCV-1b in the era of individualized therapy with peginterferon and ribavirin. Thirty-seven patients were treated with optimally tailored therapy guided by baseline viral load combined with rapid and early virological responses while 23 patients were treated without guidance and/or assigned suboptimal treatment duration. The amino acid sequences of the PKRBD were determined by PCR and sequencing. The overall sustained virological response (SVR) rate of patients who received optimally individualized therapy was 78.4%, which was better than the SVR rate of patients who received suboptimal therapy (47.8%, P = 0.015). Multivariate analysis showed that optimally individualized therapy (P = 0.019) and 80/80/80 adherence (P = 0.006) were independent favourable predictors of SVR in the entire cohort. Further sub-analysis of the predictive factors of SVR in patients treated with optimally individualized therapy showed that mutations in the 26-amino acid downstream from the ISDR (P = 0.024) were the only independent predictor of SVR. We concluded that mutations in 26-amino acid downstream portion from the ISDR remained a prognosticator of SVR in the era of optimally tailored therapy.

Topoisomerase-specific drug sensitivity in relation to cell cycle progression.

The nuclear enzyme DNA topoisomerase II catalyzes the breakage and resealing of duplex DNA and plays an important role in several genetic processes. It also mediates the DNA cleavage activity and cytotoxicity of clinically important anticancer agents such as etoposide. We have examined the activity of topoisomerase II during the first cell cycle of quiescent BALB/c 3T3 cells following serum stimulation. Etoposide-mediated DNA break frequency in vivo was used as a parameter of topoisomerase II activity, and enzyme content was assayed by immunoblotting. Density-arrested A31 cells exhibited a much lower sensitivity to the effects of etoposide than did actively proliferating cells. Upon serum stimulation of the quiescent cells, however, there was a marked increase in drug sensitivity which began during S phase and reached its peak just before mitosis. Maximal drug sensitivity during this period was 2.5 times greater than that of log-phase cells. This increase in drug sensitivity was associated with an increase in intracellular topoisomerase II content as determined by immunoblotting. The induction of topoisomerase II-mediated drug sensitivity was aborted within 1 h of exposure of cells to the protein synthesis inhibitor cycloheximide, but the DNA synthesis inhibitor aphidicolin had no effect. In contrast to the sensitivity of cells to drug-induced DNA cleavage, maximal cytotoxicity occurred during S phase. A 3-h exposure to cycloheximide before etoposide treatment resulted in nearly complete loss of cytotoxicity. Our findings indicate that topoisomerase II activity fluctuates with cell cycle progression, with peak activity occurring during the G2 phase. This increase in topoisomerase II is protein synthesis dependent and may reflect a high rate of enzyme turnover. The dissociation between maximal drug-induced DNA cleavage and cytotoxicity indicates that the topoisomerase-mediated DNA breaks may be necessary but are not sufficient for cytotoxicity and that the other factors which are particularly expressed during S phase may be important as well.

Use of a recombinant protein containing major epitopes of hnRNP G to detect anti-hnRNP G antibodies in dogs with systemic lupus erythematosus.

The objective of this study was to express major epitopes of heterogeneous nuclear ribonucleoprotein G (hnRNP G) for detecting anti-hnRNP G antibodies in dogs with systemic lupus erythematosus (SLE). HnRNP G cDNA clone was isolated from HEp-2 cells, and a DNA fragment encoding immunodominant region (residues 189-272) of hnRNP G (hnRNP Gi) was subcloned into pET32 vector to construct a prokaryotic expression plasmid named pEThnRNPGi. After induction, Escherichia coli carrying pEThnRNPGi expressed a recombinant protein of 28 kDa, comprising recombinant hnRNP Gi and fusion tag. Purified recombinant hnRNP Gi protein was further analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and its identity was confirmed. Western blot analysis showed that recombinant hnRNP Gi was specifically recognized by anti-hnRNP G positive sera of SLE dogs, and not by negative control sera. In conclusion, recombinant hnRNP Gi protein expressed in this study may serve as a useful reagent to assist in the immunological diagnosis of canine SLE.

Overexpression of dihydrodiol dehydrogenase as a prognostic marker of non-small cell lung cancer.

By using mRNA differential display to examine specimens of non-small cell lung cancer (NSCLC), we have identified overexpression of dihydrodiol dehydrogenase (DDH) that was not detected in the corresponding normal lung tissue. Normally DDH is associated with catalysis of polycyclic aromatic hydrocarbons (PAHs) in the liver; in NSCLC cells, DDH expression would implicate an association with disease progression. In this study we investigated the prognostic significance of DDH expression in patients with NSCLC. By using immunohistochemistry, we measured DDH expression in 381 patients with NSCLC. The relationship between DDH expression and clinicopathological parameters (age, gender, smoking history, mitotic index, histological type, stage, cell differentiation, and lymphovascular invasion) was analyzed by chi2 analysis. Survival curves were plotted with the method of Kaplan-Meier, and statistical difference of survivals between different groups was compared by a log-rank test. Our results showed that DDH overexpression could be detected in 317 (83.2%) of 381 pathological sections and in 77.9% (60 of 77) of metastatic lymph nodes. Expression of DDH was confirmed by immunoblotting. Compared with patients with DDH overexpression in tumors, patients with low DDH expression had significantly lower incidence of early tumor recurrence and distant organ metastasis (46.7 versus 29.7%; P = 0.045). Interestingly, survival was also significantly better in patients with low DDH expression than in those with DDH overexpression (P = 0.0017). Using univariate analysis, we correlated three important factors, DDH overexpression, tumor stages, and gender, with poor prognosis for NSCLC patients. Nevertheless, biological function and involvement of DDH in the disease progression of NSCLC require additional studies.

T-cell factor-4 and MHC upregulation in pigs receiving a live attenuated classical swine fever virus (CSFV) vaccine strain with interferon-gamma adjuvant.

The effect of co-administration of interferon (IFN)-γ in pigs undergoing vaccination with an attenuated strain (LPC) of classical swine fever virus (CSFV) was investigated. Unvaccinated pigs demonstrated pyrexia and died 7-9 days after challenge with virulent CSFV. Pigs receiving the attenuated vaccine remained healthy after virus challenge, except for mild, transient pyrexia, whereas pigs receiving IFN-γ simultaneously with the vaccine demonstrated normal body temperatures after virus challenge. Examination by nested RT-PCR revealed greater viral load in the spleens of the pigs vaccinated with the attenuated CSFV, compared with those that had additionally received IFN-γ. Expression of major histocompatibility complex (MHC) class I and MHC class II molecules was upregulated in the spleens of the IFN-γ treated vaccinated pigs, demonstrated by immunohistochemistry. Based on Western blot analysis, anti-CSFV IgG2 antibodies were elevated in vaccinated pigs by co-administration of IFN-γ (IFN-γ(Hi): P < 0.01; IFN-γ(Lo): P <0.05). By employing the suppression subtractive hybridization technique, RT-PCR, in situ hybridization, and immunohistochemistry, T-cell factor-4 (Tcf-4) mRNA and protein expression were found to be upregulated in the spleens of vaccinated pigs that had received IFN-γ. This study suggests involvement of Tcf-4 in IFN-γ-mediated immune regulation following CSFV vaccination.

Isolation and characterization of the Bacillus subtilis tryptophanyl-tRNA synthetase gene (trpS) conferring 5-fluorotryptophan resistance and temperature sensitivity.

The mutant trpS gene of Bacillus subtilis encoding a thermosensitive tryptophanyl-tRNA synthetase that also confers resistance to growth inhibition by 5-fluorotryptophan at permissive temperature has been isolated and characterized. A point mutation at codon 82 of the gene from a wild-type TCA codon for Ser to a TTA codon for Leu has been identified.

Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy.

PURPOSE: To evaluate prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the reduction of chemotherapy-induced oral mucositis. PATIENTS AND METHODS: Twenty patients with stage IV squamous cell carcinoma of head and neck were studied. Two-cycles (periods) of identical doses of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) chemotherapy with cisplatin 20 mg/m2/d, 5-FU 800 mg/m2/d, leucovorin 90 mg/m2/d by 96-hour continuous intravenous infusion every 3 weeks were given to each patient. After PFL chemotherapy, GM-CSF 4 micrograms/kg subcutaneously from days 5 to 14 or no therapy was given by a randomized self-controlled crossover study design. Oral mucositis was graded with modified Radiation Therapy Oncology Group criteria. RESULTS: In the first cycle of PFL chemotherapy, GM-CSF significantly reduced the incidence, mean duration, and mean area under the curve (AUC) of severe oral gross mucositis (grade > or = 3) compared with no therapy. These beneficial effects continued into the second cycle of PFL chemotherapy after crossover to no GM-CSF. The incidence of severe mucositis was reduced when GM-CSF was given in the second cycle of PFL. Analysis of variance indicated significant direct GM-CSF treatment effects on the mean AUC of gross/functional scores and duration of moderate gross mucositis (grade > or = 2) over both periods. There was a significant period effect in favor of giving GM-CSF in the first cycle of chemotherapy. CONCLUSION: GM-CSF can significantly reduce the severity and duration of chemotherapy-induced oral mucositis after PFL chemotherapy.

Clinical significance of serum soluble interleukin 2 receptor-alpha in esophageal squamous cell carcinoma.

Although the serum level of soluble interleukin-2 receptor alpha (sIL-2Ralpha) has been shown to correlate with progression and prognosis of several cancers, data to support its clinical significance to esophageal squamous cell carcinoma (ESCC) are limited. This study was conducted to assess the prognostic value and source of sIL-2Ralpha in patients with ESCC. From January 1986 to June 1997, 125 patients with histopathologically confirmed ESCC were enrolled for study. Ninety-three patients underwent en bloc esophagectomy, and 32 patients with unresectable tumor underwent palliative surgery. Four (4.3%; 4 of 93) patients died of surgical complications. Serum levels of sIL-2Ralpha were measured by ELISA. Expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma in the pathological section was determined, respectively, by immunohistochemistry (IHC) and in situ hybridization (ISH). Compared with the healthy control group (1020 +/-476 pg/ml, n = 103), ESCC patients tended to have significantly higher serum sIL-2Ralpha concentrations (1424 +/- 798 pg/ml, n = 121). The sIL-2Ralpha level was correlated with age, Tumor-Node-Metastasis classification, tumor stage, reading score of the IHC staining, and survival but not with the pathological grade or lymphovascular invasion. Prognosis was worse for patients with high sIL-2Ralpha levels (> or =1500 pg/ml) than for those with low serum sIL-2Ralpha levels (< 1500 pg/ml; P = 0.0209). It can be used as an independent prognostic factor of ESCC. In the pathological sections, expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma was detected in 17 (18.1%), 83 (89.2%), and 83 (89.2%) cases, respectively, by IHC, and the message of IL-2Ralpha was identified in tumor cells by ISH in 30.1% (28 of 93) of the cases. Serum concentrations of sIL-2Ralpha are frequently elevated in ESCC patients and are correlated with disease progression and survival. These data indicate that, in addition to activated T cells, cancer cells could be an important source of sIL-2Ralpha in ESCC patients.

Expression of nm23 in the primary tumor and the metastatic regional lymph nodes of patients with gastric cardiac cancer.

Tumor recurrence and distant metastasis are major causes of treatment failure in gastric cardiac cancer (GCC). Rapid growth of tumor cells and reduced expression of nm23, a metastatic suppressor gene, in tumor cells have been suggested as two important mechanisms for disease progression of GCC. Therefore, to determine the prognostic value of nm23 expression in GCC, we used immunohistochemistry to examine the expression of nm23 in the pathological sections of both gastric cancer and metastatic lymph nodes from 24 stage III patients. Twenty-two patients had total gastrectomy, and two patients had proximal subtotal gastrectomy with a D2 dissection. Postoperative adjuvant therapy was provided, and the clinical responses were followed routinely. Clinical correlation was evaluated by chi2 with Fisher's exact test and survival by log-rank test. Our results show that the reduced nm23 expression in the primary tumor and in the nodal metastasis is the most useful marker for the poor prognosis of GCC following surgery.

Cloning and nucleotide sequence of the structural gene coding for Bacillus subtilis tryptophanyl-tRNA synthetase.

A 1.47-kb DNA fragment that carries the tryptophanyl-tRNA synthetase (TrpRS) gene of Bacillus subtilis has been cloned into the pUC8 plasmid. The recombinant plasmid, pTSQ2, conferred temperature-resistance to the temperature-sensitive trpS ts mutant of B. subtilis through chromosomal transformation, and to that of Escherichia coli through complementation. The pTSQ2 could be stably maintained in E. coli DH5 alpha, causing in the host cell a 200-fold amplification of TrpRS activity. The complete nucleotide sequence of the cloned fragment has been determined. A putative transcriptional promoter, a Shine-Dalgarno sequence, the 990-bp trpS gene proper, as well as a transcriptional terminator have been identified.

In vitro replication directed by a cloned adenovirus origin.

A 5.7-kb recombinant plasmid, called XD-7, contains the terminal XbaI-E fragment from the left end of type 2 adenovirus cloned into the EcoRI site of pBR322. An average of 9% +/- 1% of input supercoiled, protein-free XD-7 DNA replicated as rolling circles with single-stranded tails ranging up to unit length and longer in reaction mixtures containing nuclear and cytoplasmic extracts from adenovirus-infected, but not uninfected, HeLa cells. The adenovirus origin was mapped on XD-7 by electron microscopy at the left boundary of the cloned adenovirus segment. Since replication proceeded rightwards, we conclude that the adenovirus l strand was displaced during replication. No origin was located at or near the EcoRI site on pBR322. Reversing the orientation of the adenovirus origin reversed the direction of replication, and deletion of the adenovirus origin abolished replication.

Mutational mapping of a cloned adenovirus origin.

We have developed a standardized, quantitative assay to study the function of a cloned adenovirus origin. We have shown that the adenovirus origin is located within the first 20 bp of the adenovirus inverted terminal repetition (ITR), a region containing a sequence conserved among human, simian, murine, and avian adenoviruses. Deletions removing or penetrating from either direction into the conserved sequence inactivated the cloned adenovirus origin. A point mutation within the conserved sequence impaired the adenovirus origin, but point mutations outside the conserved sequence had no effect. These results strongly suggest that the conserved sequence within the first 20 bp of the ITR alone constitutes the adenovirus origin (ori) signal.

Serum responses to the combination of Epstein-Barr virus antigens from both latent and acute phases in nasopharyngeal carcinoma: complementary test of EBNA-1 with EA-D.

Elevated serum IgA to antigens of EBV is associated with nasopharyngeal carcinoma (NPC). We have tested 620 NPC sera by ELISA for the presence of antibodies to EBV-encoded DNA binding protein, EBV-specific DNA polymerase, early antigen-diffused (EA-D), EBV nuclear antigen 1 (EBNA-1), EBV-specific thymidine kinase, and BamHI Z fragment EBV replication antigen. Sensitivity of these proteins was in the range of 51.5-79.5% for IgA and 69.4-82.8% for IgG. The complementary use of EBNA-1 with EA-D, however, could increase the sensitivity significantly to 98.1%. Western blot analysis further showed that the combination of EBNA-1 and EA-D is most useful for the detection of NPC. This is the first report of using double biomarkers including EBV gene products from both latent and active infections. The results of this study suggest that EBV in NPC may not be latent alone and that the method may be valuable for the early detection, early treatment, and better survival rate of patients with NPC. Because the application of recombinant EBV protein in ELISA is cost-effective and feasible for mass screening, the method may be of worth for further clinical investigation.

Abrogation of etoposide-mediated cytotoxicity by cycloheximide.

The antitumor agent etoposide interacts with DNA topoisomerase II to produce a unique form of DNA-enzyme intermediate referred to as a "cleavable complex". These drug-induced DNA strand breaks initiate poorly defined cell processes which result in lethality. To explore the mechanism of etoposide cytotoxicity, we studied the effect of protein synthesis inhibitor on Balb/C 3T3 fibroblasts and CCRF-CEM and L1210 leukemia cells by exposing these cell lines to cycloheximide for various periods of time prior to etoposide challenge. Cycloheximide alone during these periods of exposure was not cytotoxic; however, it conferred increasing cytoprotection from etoposide in a time-dependent fashion when it preceded etoposide. Although cycloheximide did cause a decrease in enzyme content and in etoposide-induced DNA cleavage of Balb/C 3T3 and the CCRF-CEM cell lines, cytoprotection by cycloheximide could not be accounted for completely by these phenomena since, in L1210 cells, cytoprotection was observed without significant change in DNA cleavage or enzyme content. Cycloheximide diminished DNA synthesis as well as protein synthesis. However, DNA synthesis resumed within 6 hr after removal of cycloheximide, in spite of the fact that cytoprotection persisted. Cycloheximide did not alter cell cycle distribution as measured by flow cytometry. Our data, therefore, clearly demonstrate that cycloheximide can diminish the cytotoxic potential of etoposide-mediated topoisomerase-DNA complexes. Elucidation of the mechanism by which cytoprotection occurs should shed light on the basis for the cytotoxic effect of topoisomerase II-active drugs.

Effect of platelet activating factor and butyrate on the expression of interleukin-2 receptor alpha in nasopharyngeal carcinoma cells.

Serum level of soluble interleukin-2 receptor alpha (sIL-2Ralpha) has been shown to correlate with disease progression and prognosis of cancer patients. However, the available information about the source and the pathophysiological regulation of IL-2Ralpha in cancer cells is limited. This study addressed the questions of prognostic value and the source of sIL-2Ralpha in patients with nasopharyngeal carcinoma (NPC). Biological regulation of IL-2Ralpha was characterized in NPC cell lines. Serum sIL-2Ralpha levels of 113 NPC patients were measured by enzyme-linked immunosorbent assay (ELISA). Levels of sIL-2Ralpha in NPC patients were significantly higher than that in the healthy controls, and sIL-2Ralpha levels were correlated with disease progression and patient survival. IL-2Ralpha was identified in cancer cells by immunocytochemistry. In vitro, IL-2Ralpha expression was markedly increased following treatment with platelet activating factor and/or n-sodium butyrate. Increased secretion of IL-2Ralpha was also detected in the culture media. The secreted IL-2Ralpha could functionally bind IL-2. These results indicate that elevated sIL-2Ralpha was often detected in patients with advanced NPC. The elevated sIL-2Ralpha could be shed from NPC cells by a yet to be determined mechanism and IL-2Ralpha expression in NPC cells could be upregulated by platelet activating factor and butyrate.

Fatal pulmonary fibrosis associated with BCNU: the relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-beta1 and cyclooxygenase-2.

Pulmonary fibrosis is a severe complication associated with bis-chloronitrosourea (BCNU) therapy. However, the pathogenetic mechanism has never been well investigated. We report here a 26-year-old female with diffuse large B-cell lymphoma who died of severe pulmonary fibrosis 81 days after the administration of high-dose BCNU (600 mg/m2). Thoracoscopic wedge resection of left upper lung performed 10 days before patient's death showed severe pulmonary fibrosis with prominent hyperplasia of alveolar macrophages and type II pneumocytes. We further used immunohistochemistry (IHC) to examine the relative role of platelet-derived growth factor-B (PDGF-B), insulin-like growth factor I (IGF-I), transforming growth factor-beta1 (TGF-beta1) and cyclooxygenase-2 (COX-2) in the pathogenesis of BCNU-related pulmonary fibrosis. Strong expressions of PDGF-B and IGF-1 on alveolar macrophages and type II pneumocytes were clearly demonstrated, but in contrast, the expressions of TGF-beta1 and COX-2 were almost undetectable. In conclusion, pulmonary fibrosis can develop early and progress rapidly after the administration of high-dose BCNU. The markedly increased expression of fibrogenic factors PDGF-B and IGF-1 on hyperplastic alveolar macrophages and hyperplastic type II pneumocytes may play an important role in the fibrogenesis of this disease. These novel findings may offer specific therapeutic targets in the treatment of BCNU-associated pulmonary fibrosis.

Virus infection in patients with histiocytic necrotizing lymphadenitis in Taiwan. Detection of Epstein-Barr virus, type I human T-cell lymphotropic virus, and parvovirus B19.

The relationship of Epstein-Barr virus (EBV), type I human T-cell lymphotropic virus (HTLV-I), and parvovirus B19 to histiocytic necrotizing lymphadenitis was studied prospectively in 10 Taiwanese patients using materials obtained by fine-needle aspiration and lymph node biopsy. The presence of EBV was detected by in situ hybridization for EBV-encoded RNA expression. Immunocytochemistry was used to detect virus-encoded protein for EBV and parvovirus B19. DNA in situ hybridization and polymerase chain reaction were performed to determine the existence of HTLV-I provirus. Expressions of EBV-encoded RNA and Fas ligand were detected in all cases. Expression of EBV-encoded protein was identified in only 1 case. Neither HTLV-I nor parvovirus B19 was detected in any case.

Gastrointestinal bleeding and mycotic superior mesenteric aneurysm.

This is a case report of management of a delayed mycotic superior mesenteric artery aneurysm occurring in a patient 2 years after aortic valve replacement for endocarditis. A chronic ulcer history, anticoagulation therapy, episodic gastrointestinal bleeding associated with negative gastrointestinal series, and gastritis seen at endoscopy delayed the ultimate diagnosis. An episode of massive hemorrhage precipitated angiography with subsequent surgical confirmation of the diagnosis. Management included debridement and extirpation of the major part of the aneurysm, Doppler assessment of the inadequacy of collateral mesenteric arterial blood flow, and restoration of flow with a bypassing saphenous vein graft segment. Although this technique of reconstruction has been suggested, we can find no other report of such a similar case among the few reported surgical successes with superior mesenteric artery mycotic aneurysm.