Impacts of HIV infection and long-term use of antiretroviral therapy on the prevalence of oral human papilloma virus type 16

J Oral Pathol Med (2012) 41 : 309–314 Background: The objectives of this study were to determine (i) the prevalence and the copy numbers of oral human papilloma virus type 16 (HPV‐16) in HIV‐infected patients compared with non‐HIV controls, and (ii) the effects of antiretroviral therapy (ART) and its duration on the virus. Methods: A cross‐sectional study was carried out in HIV‐infected patients with and without ART and in non‐HIV controls. Saliva samples were collected, and the DNA extracted from those samples was used as a template to detect HPV‐16 E6 and E7 by quantitative polymerase chain reaction. Student’s t‐test and ANOVA test were performed to determine the prevalence rates among groups. Results: Forty‐nine HIV‐infected patients: 37 on ART (age range, 23–54 years; mean, 37 years), 12 not on ART (age range, 20–40 years; mean, 31 years), and 20 non‐HIV controls (age range, 19–53 years; mean, 31 years) were enrolled. The prevalence of oral HPV‐16 infection and the copy numbers of the virus were significantly higher in HIV‐infected patients than in non‐HIV controls when using E6 assay (geometric mean = 10696 vs. 563 copies/10⁵ cells, P < 0.001), but not E7 assay. No significant difference was observed between those who were and were not on ART. Long‐term use of ART did not significantly change the prevalence of oral HPV‐16 infection and the copy numbers of the virus (P = 0.567). Conclusion: We conclude that the prevalence of oral HPV‐16 infection and the copy numbers of the virus are increased by HIV infection. Neither the use of ART nor its duration significantly affected the virus.     

Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma

Purpose To assess the status of EGFR, HER-2, and CCND1 at the gene and protein levels in esophageal squamous cell carcinoma.Methods Dual-color FISH assays were performed using DNA probes for EGFR/CEP 7, HER-2/CEP 17, and CCND1/CEP 11. The respective proteins, furthermore, was assessed in IHC assays and correlated with patient and tumor characteristics.Results From 55 ESCCs, 8 (15%) tumors showed gene amplification and 20 (36%) had gene overrepresentation (balanced gene and chromosome 7 polysomy) for EGFR. High-level protein expression was frequent (49%), positively correlated with gene copy numbers (kappa=0.4), and associated with well-differentiated histology (p=0.02). For HER-2, gene amplification was detected in a single tumor (2%) and protein overexpression was rare (9%). CCND1 gene was amplified in 23 (42%) tumors; likewise, CCND1 protein overexpression was common (58%) and prevailed in gene overrepresentation or amplification. Only 1 patient showed gene amplification for both EGFR and CCND1. Survival was not associated with EGFR or CCND1 gene/protein status, whereas negative patients for HER-2 protein had a better survival than positive patients (p=0.04).Conclusions Frequent overexpression and gene amplification of EGFR and CCND1 make these molecules and their pathways potential therapeutic targets for ESCC. In addition, EGFR and CCND1 appeared to be independently altered suggesting alternative mechanisms for pathway activation. Therapeutic agents targeting these molecules are urged to be tested in clinical trials and comprehensive biological analyses should be included to properly interpret the outcome.     

Prenatal diagnosis of deletion of chromosome 6p presenting with hydrops fetalis

OBJECTIVE: To report the first known case of 6p deletion presenting in utero with hydrops fetalis and multiple anomalies in the second trimester of pregnancy. METHODS: A thirty-year-old woman (gravida 3 para 1 abortion 1) was referred to our hospital at 18 weeks of gestation because of suspicion of fetal anomaly on routine ultrasound examination. A detailed anomaly scan revealed a single viable fetus with marked skin edema, marked ascites, pleural effusion, hydronephrosis of left kidney, absence of right kidney, cardiac anomaly and oligohydramnios. The fetal face was not visible due to the fetal position. Fetal karyotyping revealed 46,XX,del(6)(p21.3). The couple opted to terminate the pregnancy. RESULTS: A hydropic female fetus was aborted and the autopsy revealed hydrops fetalis with bilateral cleft lips, hydronephrosis of left kidney, absence of right kidney, spleen, and thymus gland, truncus arteriosus, and single umbilical artery. Cord blood and tissue culture confirmed that the fetus had deletion of chromosome 6p. CONCLUSION: Deletion of short arm of chromosome 6 can result in hydrops fetalis in early pregnancy.     

High tumor necrosis factor-alpha levels in the patients with Epstein-Barr virus-associated peripheral T-cell proliferative disease/lymphoma

We have attempted to find out any relationships between circulating tumor necrosis factor (TNF)-alpha levels and Epstein-Barr virus (EBV) associated peripheral T-cell and NK-cell proliferative disease/lymphoma (PTPD/L) status. The distribution of TNF-alpha level was significantly higher (P<0.05) in patients than in controls. Patients carrying EBV genome in their peripheral T-cells showed higher TNF-alpha levels than the patients with EBV negative peripheral T-cells (P<0.001). Among patients whose peripheral T-cells were positive for EBV genome, TNF-alpha levels between the wild type LMP-1 gene carriers and the 30-bp deletion type LMP-1 gene carriers were compared and the wild type LMP-1 gene carrier group showed significantly higher TNF-alpha levels (P<0.01). As for the outcome of the patients and TNF-alpha levels, significant differences were observed between dead and alive with disease group (P<0.001), and dead and alive with complete remission group (P<0.01). Since circulating TNF-alpha levels in PTPD/L patients correlate with the disease and EBV infection status, it may be possible that monitoring of the TNF-alpha levels will be a useful prognostic marker.     

Absence of Epstein-Barr virus in esophageal squamous cell carcinoma

It is strongly suspected that the Epstein-Barr virus (EBV) plays a role in the genesis of nasopharyngeal and gastric carcinoma. The aim of this study was to search for such a connection between esophageal squamous cell carcinoma (ESCC) and EBV. We investigated 104 surgically resected esophageal cancers using in situ hybridization (ISH) for EBV-encoded RNA (EBER). We found no EBER-positive cancer cells in any tests, although there were five samples in which EBER-positive tumor-infiltrating lymphocytes (TILs) were found. We conclude from this study that EBV is not associated with ESCC.     

Non-fatal acute renal failure due to wasp stings in children

We report two children who developed acute renal failure after multiple wasp stings. Each case involved intravascular hemolysis which caused acute renal failure, volume overload, hypertension, anemia, hyponatremia, hyperkalemia, and metabolic acidosis. Peritoneal dialysis was required for short periods. The children recovered completely with blood urea nitrogen and creatinine returning to normal within 3 months. One child had a renal biopsy which showed mild tubulointerstitial nephritis. Although there is no specific treatment or antivenom, dialysis and supportive care have proved to be successful. Received February 4, 1997; received in revised form June 23, 1997; accepted July 2, 1997     

中草药“再生丹”对HIV感染者的疗效观察

目的　探讨中草药“再生丹”对ＨＩＶ感染者的治疗作用。方法　采用中药复合治疗方法，主药用于提高机体免疫力，辅药对症治疗。观察临床症状、实验室检测ＣＤ４ 和ＣＤ８ 淋巴细胞数，以及外周血中病毒载量的变化，并与治疗前比较。结果　２８ 例ＨＩＶ感染者服药后，体重有不同程度增加，平均增加５－４ ｋｇ。７ 例长期发热，４ 例腹泻，２ 例大面积皮肤溃烂和１ 例皮疹患者，服药１ 个月后症状消失；服药后５ 个月，１０ 例表现淋巴结肿大的患者中，３ 例肿大的淋巴结消失，７ 例显示不同程度的数量减少或体积缩小。治疗后２ 个月，４２－９％ 患者表现ＣＤ４ 淋巴细胞数增加，７１－４％ 患者病毒载量下降。治疗５ 个月后，ＣＤ４ 淋巴细胞增加者占５０－０％ ，８０－０％ 患者病毒载量下降，综合分析临床症状和实验室指标，总有效率达９４－０％ 。结论　中草药复合治疗ＨＩＶ感染者，可明显改善临床症状，提高ＣＤ４ 细胞数，使病毒载量下降，为用中草药控制ＨＩＶ感染和治疗艾滋病患者提供证据     

Tubulointerstitial renal failure in childhood leptospirosis.

We report three children with tubulointerstitial renal failure following leptospirosis. All had acute nonoliguric renal failure with mild hypocalemia and mild metabolic acidosis. Maximum blood urea nitrogen (BUN) and creatinine were 217 and 7.1 mg/dl, respectively, on the 6th day of disease, and no patient required dialysis. They presented with acute febrile illness and dehydration, and required intravenous fluid supplements. Myalgia, vomiting, and bleeding were found in two children. Abdominal pain, arthralgia, diarrhea, and conjunctival suffusion were found in one child. Only one child, who had an underlying disease of beta-thalassemia/Hb E, had jaundice, hepatosplenomegaly, anemia, and thrombocytopenia. Penicillin treatment was given in one case. All recovered, with normal renal function. The leptospirosis complement fixation test was used to confirm diagnosis. L. batavia was considered the etiologic agent in two of the children.     

Epstein-Barr virus-associated peripheral T-cell and NK-cell proliferative disease/lymphoma: clinicopathologic, serologic, and molecular analysis

Peripheral T-cell proliferative disease/lymphoma is a group of diseases which exhibits heterogeneity in clinical manifestations, pathological findings and outcomes. They are highly associated with the Epstein-Barr virus (EBV) infection. It is likely that EBV plays an important role in the tumorigenesis. From January 1997 through April 2000, we identified 100 patients. One hundred healthy age- and sex- matched controls were selected. Serologic tests for the EBV infection and the study of EBV genomes in circulating non-T cells (CD3- cells), T cells (CD3+ cells), and T-cell subsets (CD4+ and CD8+ cells) were performed. The main features were prolonged fever, weight loss, hepatosplenomegaly, lymphadenopathy, multiorgan involvement, anemia, and high serum alkaline phosphatase and lactate dehydrogenase. Fifty-one patients had an aggressive course and died; median survival was 21 months. Chemotherapy was not effective in improving survival. Anti-viral capsid antigen-IgG and anti-early antigen-IgG were significantly elevated, whereas there was no significant difference in anti-EBV nuclear antigen. EBV internal repeat-1 region (IR-1) in the peripheral blood CD3+ cells was detected in 65% of the patients but in none of the controls. For the CD3- cells, EBV IR-1 was detected in 88% of the patients and 50% of the controls. Among twenty-five patients whose CD3+ cells were positive for EBV IR-1, 6 (24%) showed EBV IR-1 in only CD4+ cells, 6 (24%) in only CD8+ cells, and 13 (52%) in both CD4+ and CD8+ cells. The 30-bp deletion variant of the EBV latent membrane protein-1 gene was significantly higher in the patients than in the controls. These data support the chronic infective process. The EBV which is dormant in non-T cells may infect T cells and contribute to the pathogenesis of disease in a select group of patients.