Epstein-Barr viral load as a marker of lymphoma in AIDS patients

Epstein-Barr virus (EBV) is implicated in the pathogenesis of acquired immunodeficiency syndrome (AIDS) lymphoma, and viral DNA is present within the malignant cells in about half of affected patients. We examined the extent to which EBV viral load is elevated in the plasma of AIDS lymphoma patients compared to AIDS patients with opportunistic infections. Sixty-one AIDS patients were studied including 35 with lymphoma (24 non-Hodgkin, six Hodgkin, and five brain lymphoma) and 26 with various opportunistic infections. In situ hybridization revealed EBV encoded RNA (EBER) expression in the malignant cells of 17/28 AIDS lymphomas (61%). In 232 serial plasma samples from 35 lymphoma patients and in 128 samples from AIDS controls, EBV viral load was assayed by quantitative-polymerase chain reaction (Q-PCR) using a TaqMan probe targeting the BamH1W sequence. EBV was detected in plasma from all 17 EBER-positive AIDS lymphoma patients, with viral loads ranging from 34 to 1,500,000 copies per ml (median 3,210). Viral load usually fell rapidly upon initiation of lymphoma therapy and remained undetectable except in two patients with persistent tumor. In 11 AIDS patients, whose lymphoma lacked EBER expression, and in 26 control patients without lymphoma, levels of EBV in plasma were usually low or undetectable (range 0-1,995 and 0-2,409, median 0 and 0, respectively). There was no association between EBV viral load and human immunodeficiency virus (HIV) load or CD4 count. In conclusion, EBV viral load shows promise as a tool to assist in diagnosis and management of EBV-related lymphoma patients.     

Effect of Heat-Killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome

Non-viable bacteria, referred to as “paraprobiotics,” have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.     

Does multidetector computed tomographic urography (MDCTU) T staging classification correspond with pathologic T staging in upper tract urothelial carcinoma?

International Urology and Nephrology - Multidetector computed tomographic urography (MDCTU) is not yet sufficient to be used in the clinical staging of upper tract urothelial carcinoma (UTUC). This...     

Editorial Commentary: Stem Cell Treatment in Knee Osteoarthritis: What for? Pain Management or Cartilage Regeneration?

The efficacy of mesenchymal stem cells regarding clinical outcomes and cartilage regeneration in knee osteoarthritis remains unclear; however, their theoretical role in multilineage cellular differentiation and immunomodulation of the arthritic cascade has been investigated. Several studies have reported that the use of stem cell therapy for knee osteoarthritis helps in pain improvement, but its effect on cartilage regeneration has not yet been explored. Moreover, numerous studies have reported high heterogeneity in the cell sources, as well as methods of culture expansion or cell concentration, and differences in delivery methods, assessment tools, and concomitant surgical procedures, which could affect the clinical outcomes or evaluation of cartilage regeneration potency. Furthermore, future studies are warranted to examine these factors in detail to interpret the results of mesenchymal stem cell treatment for knee osteoarthritis.     

Double hernia in continuous ambulatory peritoneal dialysis patient

Clinical and Experimental Nephrology -     

The role of Ureaplasma parvum serovar-3 or serovar-14 infection in female patients with chronic micturition urethral pain and recurrent microscopic hematuria

BackgroundUreaplasma parvum (UP) is commonly isolated in the genitor-urinary tract and may cause various clinical features, including microscopic hematuria (MH). Some UP serovars are more commonly related with specific urogenital disease, but the evidences have been conflicting. This study primarily aimed to research the possible associations between specific UP serotypes and genito-urinary pathogenicity in female patients showing MH with/without chronic micturition urethral pain (CMP).MethodsThis study retrospectively reviewed 276 female patients having MH with/without CMP, who visited health screening center or female infertility clinic. All patients underwent multiplex polymerase chain reaction (PCR) tests with vaginal and urine samples to evaluate the infection rate and serotypes of UP. The antimicrobial susceptibility of UP and the predictors of CMP among UP infected patients were also analyzed. All patients were followed up at least for 6-months.ResultsForty-nine patients (17.8%) showed urinary UP infection. Urinary UP serotyping showed the prevalence of seorvar-1, -3, -6 and -14 were 24.5%, 30.6%, 18.4% and 26.5%, respectively. 79.6% of the urinary UP positive patients accompanied vaginal UP infection. 22 patients of the cohort (8.0%) had CMP whereas serovars-3 and -14 accompanied CMP in 54.5% and 41.0% cases, respectively. No serovars-6 infection case had CMP. 26.4% of the cohort were infertile whereas 10.9% of these infertile patients were positive for urinary tract infection with UP serotype-3 or -14. Doxycycline, josamycin and pristinamycin were the most active antibiotics with the lowest rate of resistance (0.0%) for treating UP. At 1-month post-initial treatment with doxycycline, all UP serotypes were eradicated and no patient complained of urethral discomfort. However, simultaneous urinary and vaginal reinfection of serovar-3 (5 cases) and serovar-5 (1 case) were confirmed at 3-months post-initial doxycycline therapy. The logistic regression analyses revealed that serovars-3 [hazard ratio (HR) 1.354, P value 0.018] and -14 (HR 1.103, P value 0.046) were significantly associated with CMP in female patients having MH.ConclusionsUP serovars-3 and -14 infections could be associated with CMP in female patients having MH. Doxycycline, josamycin and pristinamycin were effective for treating UP. Serovar-3 showed higher reinfection rate than other serotypes after antibiotics treatment.     

Behavioral characteristics of a mouse model of cancer pain

Pain is a major symptom in cancer patients, and most cancer patients with advanced or terminal cancers suffer from chronic pain related to treatment failure and/or tumor progression. In the present study, we examined the development of cancer pain in mice. Murine hepatocarcinoma cells, HCa-1, were inoculated unilaterally into the thigh or the dorsum of the foot of male C3H/HeJ mice. Four weeks after inoculation, behavioral signs were observed for mechanical allodynia, cold allodynia, and hyperalgesia using a von Frey filament, acetone, and radiant heat, respectively. Bone invasion by the tumor commenced from 7 days after inoculation of tumor cells and was evident from 14 days after inoculation. Cold allodynia but neither mechanical allodynia nor hyperalgesia was observed in mice that received an inoculation into the thigh. On the contrary, mechanical allodynia and cold allodynia, but not hyperalgesia, were developed in mice with an inoculation into the foot. Sometimes, mirror-image pain was developed in these animals. These results suggest that carcinoma cells injected into the foot of mice may develop severe chronic pain related to cancer. This animal model of pain would be useful to elucidate the mechanisms of cancer pain in humans.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Changes of nitric oxide synthase activity and free methylarginines contents in regenerating rat liver after partial hepatectomy

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that N^G-monomethyl-L-arginine (MMA) and N^G, N^G-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.