The clinical characteristics and manifestations of cytomegalovirus esophagitis.

Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, are on long-term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end-stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23-84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment-related complication of CCRT.

The role of XRCC6/Ku70 in nasopharyngeal carcinoma.

The association between XRCC6/Ku70, an upstream player in the DNA double-strand break repair system, and the risk of nasopharyngeal carcinoma (NPC) was examined. In this case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with NPC risk were evaluated. NPC tissue samples were also assessed for their XRCC6 mRNA and protein expression by real-time quantitative reverse transcription PCR and Western blotting, respectively. With regard to the XRCC6 promoter T-991C, the TC and CC genotypes were associated with a significantly increased risk of NPC compared with wild-type TT genotype (adjusted odds ratio 2.02 and 3.42, 95% confidence interval 1.21-3.32 and 1.28-8.94, P=0.0072 and 0.0165, respectively). The mRNA and protein expression levels for NPC tissues revealed significantly lower XRCC6 mRNA and protein expression in the NPC samples with TC/CC genotypes compared to those with the TT genotype (P=0.0210 and 0.0164, respectively). These findings suggest that XRCC6 may play an important role in the carcinogenesis of NPC and could serve as a chemotherapeutic target for personalized medicine and therapy.

Timing of gangrene tissue debridement after autologous bone marrow cell implantation in patients with superficial femoral arterial occlusion: preliminary experiences.

AIM: Although implantation of bone marrow mononuclear cells (BMI) was shown to improve outcomes in patients with severe peripheral arterial occlusive disease (PAOD), little experience has been reported in patients with an arterial occlusion level above the knee, ischemic gangrene, and high cardiovascular risk. This study sought to investigate the timing of gangrene tissue debridement and the safety of BMI in these patients. METHODS: Six "no-option" PAOD patients were enrolled with an arterial occlusion level above the knee, ischemic gangrene, and 3 systemic diseases related to a high cardiovascular risk. The ischemic status was evaluated by measuring the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and wound healing after BMI. RESULTS: All patients safely underwent the procedures with intravenous general anesthesia by titrating propofol. Major lower extremity amputation, minor debridement amputation, and debridement surgery were performed in 2 (33.3%), 1 (16.7%), and 2 (33.3%) patients, respectively, 3.1 2.8 months after BMI. Compared to the amputation group (N=3), the salvage group (N=3) had a significantly higher baseline ABI (P=0.02) and a shorter distance between the gangrene site and arterial occlusion site (P=0.01). In the 3 patients who underwent debridement, ABI and TcPO2 significantly improved 1 month after BMI, and gangrenous tissues were debrided 3.8 ± 3.6 (range, 1~8) months after BMI with complete healing within 1 month. CONCLUSION: Autologous BMI therapy is safe in patients at high cardiovascular risk with an arterial occlusion level above the knee and ischemic gangrene. Effective predictors of BMI include the baseline ABI and distance to the ischemia. Gangrene tissue should be debrided at least 1 month after BMI.

Marsupialisation and strap muscle transposition laryngoplasty for vocal cysts with vocal fold atrophy.

OBJECTIVES: Vocal cysts with fold atrophy often result in more severe glottal incompetence than vocal cysts along during phonation. Although total excision or marsupialisation are reliable treatments for vocal fold cysts, any post-operative vocal deficit with significant glottal gap will need further treatment. This study aimed to evaluate the efficacy of combined treatment consisting of marsupialisation of the cyst immediately followed by strap muscle transposition laryngoplasty. METHOD: Under direct laryngomicroscopy, microscissors were used to make a disc-shaped incision encircling the equator of the cyst. After marsupialisation of the cyst, a simultaneous medialisation laryngoplasty with strap muscle transposition was performed. RESULTS: Seven patients with vocal cysts and marked vocal fold atrophy were included in the study. After surgery, subjective improvement in voice quality was reported by all patients. Patients' glottal incompetence and vocal performance were markedly improved. CONCLUSION: Marsupialisation is a simple and effective surgical technique for vocal fold cysts. For cases of vocal cysts with marked vocal fold atrophy, marsupialisation followed by medialisation laryngoplasty with strap muscle transposition may be considered.

TNF receptor I polymorphism is associated with persistent palindromic rheumatism.

OBJECTIVES: To investigate the association between tumour necrosis factor-alpha (TNFalpha), TNF receptor superfamily member 1A (TNFRSF1A, also known as TNFRI), TNFRSF1B (TNFRII), and interleukin-1beta (IL-1beta) single nucleotide polymorphisms (SNPs) and the susceptibility to persistent palindromic rheumatism (PR). METHODS: Fifty-six unrelated patients with persistent PR and 100 unrelated healthy controls were genotyped for TNFalpha -308G/A, -238G/A, and +488G/A, TNFRSF1A -609G/T and +36A/G, TNFRSF1B +676T/G and +1663G/A, and IL-1beta -511C/T, -31T/C, and +3954C/T using real-time polymerase chain reaction (RT-PCR). RESULTS: The TNFRSF1A +36G allele [odds ratio (OR) = 3.94, p = 0.003, corrected p (p(c)) = 0.03] and the TNFRSF1A +36AG genotype (OR = 4.81, p = 0.002, p(c) = 0.04) were significantly associated with persistent PR. The frequency of TNFRSF1B +676T/+1663A was increased in PR patients (OR = 2.12, p = 0.01), but failed to reach statistical significance after Bonferroni correction. No correlation was observed between persistent PR and TNFalpha, TNFRSF1A -609G/T, or IL-1beta SNPs. CONCLUSIONS: The results of this study provide evidence of an association between persistent PR and SNPs within the TNFRSF1A gene, and suggest that TNFRI is involved in the aetiopathogenesis of PR.

Evaluation of TNF-alpha and IL-1beta polymorphisms in Taiwan Chinese patients with pterygium.

PURPOSE: Pterygium, a complex disease, is associated with ultraviolet radiation, immunoinflammatory process, genetic factors, and virus infection. Ultraviolet radiation induces secretion of proinflammatory cytokines by the ocular surface epithelium, inflammatory cells in the tear fluid, or both. Among these cytokines, tumour necrosis factor (TNF)alpha and interleukin (IL)-1beta activate pterygium body fibroblasts, resulting in a phenotype capable of expressing various proteinases associated with extracellular matrix remodelling, angiogenesis, and fibroblast proliferation, which are important for pterygium formation and recurrence. The genetic factor was proposed to play a role in pterygium formation, but there were few studies to clarify this proposition. For investigating genetic factors, the association between pterygium and TNF-alpha and IL-1beta polymorphisms is evaluated in this study. METHODS: A total of 128 pterygium patients and 103 volunteers without pterygium were enrolled in this study. Polymerase chain reaction-based analysis was used to resolve the TNF-alpha-308 promoter, IL-1beta-511 promoter, IL-1beta exon 5, and IL-1 receptor antagonist (IL-1 Ra) polymorphisms. RESULTS: There were no significant differences in the frequency of genotypes and alleles of TNF-alpha-308 promoter, IL-1beta-511 promoter, IL-1beta exon 5, and IL-1 Ra polymorphisms between both groups. CONCLUSIONS: The correlation between pterygium and TNF-alpha-308 promoter, IL-1beta-511 promoter, IL-1beta exon 5, and IL-1 Ra polymorphisms does not exist and those polymorphisms are not useful genetic markers for pterygium susceptibility. Further studies on other polymorphisms or haplotypes of TNF-alpha and IL-1beta are necessary.

Inhibition of inducible nitric oxide synthase (iNOS) prevents lung neutrophil deposition and damage in burned rats.

This study was designed to investigate the role of NO and effect of iNOS inhibitor on the lung neutrophil deposition and damage after burn. In Experiment 1, specific pathogen-free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. On the 4th, 8th, 16th, and 24th h after burn, blood was collected for peroxynitrite-mediated dihydrorhodamine 123 (DHR 123) oxidation assay, and lung tissues were harvested for myeloperoxidase (MPO) test and histologic study. Pulmonary microvascular dysfunction was quantitated by measuring the extravasation of Evans blue dye (EBD). In Experiment 2, S-methylisothiourea (SMT) was given (7.5 mg/kg, intraperitoneal immediately post-burn) to suppress iNOS activity. On the 8th h after burn, the effect of SMT on blood DHR 123 oxidation, lung MPO, lung damage, and lung iNOS expression were evaluated. Lung MPO activity increased up to a maximum of 2-fold 8 h after burn. Blood DHR 123 oxidation increased up to a maximum of 2-fold 8 h after burn. Lung permeability increased up to a maximum of 2.5-fold 4 h after burn. SMT significantly decreased lung MPO activity, blood DHR 123 oxidation, and lung permeability by 31%, 41%, and 54%, respectively. SMT markedly decreased the thermal injury-induced perivascular and interstitial inflammatory cell infiltration and iNOS staining in bronchiolar epithelium, endothelial cells, and perivascular and interstitial inflammatory cells. In conclusion, thermal injury induces blood DHR 123 oxidation, lung neutrophil deposition, lung iNOS expression, and lung damage. Peroxynitrite might play an important role in thermal injury-induced lung neutrophil deposition and damage. Specific inhibition of lung iNOS expression and blood DHR 123 oxidation with SMT on thermal injury not only attenuated the lung neutrophil deposition, but also reduced lung damage.

Pituitary adenylate cyclase-activating polypeptide regulation of vasoactive intestinal polypeptide transcription requires Ca2+ influx and activation of the serine/threonine phosphatase calcineurin.

A >15-fold increase in vasoactive intestinal polypeptide (VIP) mRNA and VIP peptide levels occurred in primary chromaffin cells following exposure to the neurotrophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)-27 with an EC50 of approximately 2 nM. PACAP induction of VIP expression was blocked by methoxyverapamil or by a combination of nimodipine and omega-conotoxin MVIIC, indicating a requirement for PACAP-initiated calcium entry through voltage-dependent calcium channels for regulation of VIP biosynthesis. Ascomycin, which inhibits calcineurin through formation of an ascomycin/FKBP12/calcineurin ternary complex, abolished the PACAP-evoked increase in VIP expression, whereas rapamycin, which also binds to FKBP12 but does not cause inhibition of calcineurin, did not. Cyclosporin A, which inhibits calcineurin through formation of a cyclosporin A/cyclophilin/calcineurin complex, also abolished PACAP-evoked VIP biosynthesis. These data indicate that PACAP regulates the expression of VIP via a signaling pathway that requires calcium influx and activation of calcineurin.

PACAP activates calcium influx-dependent and -independent pathways to couple met-enkephalin secretion and biosynthesis in chromaffin cells.

Pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) caused a dose-dependent increase in met-enkephalin secretion and increased production of met-enkephalin peptide and proenkephalin A (PEnk) mRNA in bovine chromaffin cells, at concentrations as low as 300 pM. PACAP-38 was less potent than PACAP-27, but had similar effects. Vasoactive intestinal polypeptide (VIP) (1-100 nM) was without appreciable effect on either enkephalin secretion or biosynthesis, implicating PACAP type I receptors in PACAP-stimulated enkephalin secretion and synthesis. PACAP type I receptors can activate adenylate cyclase and stimulate phospholipase C through heterotrimeric G protein interactions, leading to increased intracellular cyclic AMP (cAMP), inositol triphosphate (IP3)-mediated calcium mobilization, and calcium- and diacylglycerol (DAG)-mediated protein kinase C (PKC) activation. Enkephalin secretion evoked by 10-100 nM PACAP-27 was not inhibited by 1 microM (-)-202-791, an L-type specific dihydropyridine calcium channel blocker, but was inhibited 65-80% by the arylalkylamine calcium channel blocker D600. Forty mM potassium-evoked secretion was inhibited > 90% by both D600 and (-)-202-791, 25 microM forskolin-induced secretion was blocked < 50% by D600 and was unaffected by (-)-202-791, and 100 nM phorbol myristate acetate (PMA)-induced secretion was unaffected by either D600 or (-)-202-791. Enkephalin biosynthesis was increased by 10 nM PACAP-27, as measured by increased met-enkephalin pentapeptide content and PEnk A mRNA levels. PACAP-, forskolin-, and PMA-stimulated enkephalin synthesis were not blocked by D600 or (-)-202-791. Elevated potassium-induced enkephalin biosynthesis upregulation was completely blocked by either D600 or (-)-202-791 at the same concentrations. PACAP acting through type I PACAP receptors couples calcium influx-dependent enkephalin secretion and calcium influx-independent enkephalin biosynthesis in chromaffin cells. Restriction of the effects of enhanced calcium influx to stimulation of secretion, but not of biosynthesis, is unique to PACAP. By contrast, potassium-induced enkephalin biosynthesis upregulation is completely calcium influx dependent, specifically via calcium influx through L-type calcium channels. We propose that subpopulations of voltage-dependent calcium channels are differentially linked to intracellular signal transduction pathways that control neuropeptide gene expression and secretion in chromaffin cells.

Seroepidemiological study of measles after the 1992 nationwide MMR revaccination program in Taiwan.

The incidence of measles declined rapidly in Taiwan after the introduction of the measles vaccine into the routine immunization schedule in 1978. However, an epidemic still occurred every 3-5 years until recently. A nationwide measles-mumps-rubella (MMR) revaccination program for school and preschool children has been in place since 1992 to control the indigenous transmission of measles. In order to understand the current immune status after this recent nationwide revaccination program, we determined the presence of measles IgG antibodies by enzyme-linked immunosorbent assay (ELISA) in 1,281 blood samples from healthy persons aged from 2 months to above 30 years collected between 1993 and 1995, and also in another batch of 90 sera samples from children aged 2 years collected before 1992. The results showed that 1) the measles antibody seropositive rate (36.4%) was lowest in children aged 5-7 months and rose to an unexpectedly high level of 85.8% at the age of 12-14 months, 2) the seropositive rate rose further to between 85.9% and 95.1% after 2 years of age and remained high in adults and pregnant women, and 3) the seropositive rate of the 2-year-old children collected before 1992 was 61.4%, which was significantly lower than the rate of the same age group collected after the nationwide MMR revaccination program. We conclude that the national revaccination program has promoted effectively measles immunity in Taiwan. This immunity explains the rarity of reported measles cases since the last epidemic in 1989. This revaccination program should continue and be extended to all preschool children and young adults so that indigenous measles can be eliminated by the year 2000.

Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations.

BACKGROUND: Conventional and modified ultrafiltration was used in pediatric cardiac operations to reduce volume overload and total body water. The purpose of this study was to compare the efficacy of these techniques in removing inflammatory mediators during cardiopulmonary bypass. METHODS: Fifty pediatric patients undergoing cardiac operations were randomized into a modified or conventional ultrafiltration group. Blood samples were obtained before and after ultrafiltration to assess the plasma concentrations of leukocyte elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8. RESULTS: Except for plasma concentrations of tumor necrosis factor-alpha in the modified ultrafiltration group, the plasma concentrations of all the mediators measured increased after ultrafiltration in both groups of patients. The volume of ultrafiltrate and the total amounts of tumor necrosis factor-alpha and interleukin-6 removed by ultrafiltration were significantly greater in the modified group. The concentrations of mediators in the ultrafiltrate and the ratio of ultrafiltrate to plasma concentrations of the mediators did not differ between the groups. Ultrafiltration was more efficient in removing tumor necrosis factor-alpha than the other mediators. CONCLUSIONS: The efficacy in removing the inflammatory mediators generated during cardiopulmonary bypass did not differ between modified and conventional ultrafiltration.

Coexisting IgA nephropathy and leukocytoclastic cutaneous vasculitis associated with ankylosing spondylitis: a case report.

A patient with ankylosing spondylitis and coexisting IgA nephropathy and leukocytoclastic cutaneous vasculitis is described. Renal biopsy demonstrated mesangial proliferative glomerulonephritis with prominent IgA, C3 and fibrin deposition in the glomeruli. Simultaneously, leukocytoclastic cutaneous vasculitis with prominent IgG, IgA and C3 deposition of dermal vessel wall was also observed in the skin biopsy specimen. Such associations have been previously reported in only four cases. This report once again indicates that antigenic mucosal stimulation may play an important role in the pathogenesis of ankylosing spondylitis.

An experimental model of osteoarthritis in rabbit.

BACKGROUND: From both a microscopic and a metabolic view, experimental animal models are very important for study of the pathogenesis of osteoarthritis. A new, different operative procedure was used in rabbit models, and the pathologic findings were evaluated. METHODS: Twelve New Zealand white rabbits were divided into six groups; eight were used as animal models and four, for drug efficacy study. Transection of the anterior cruciate and medial collateral ligaments on the left knee joint, and sham-operation were performed on the right knee joint. Rabbits were sacrificed post surgery from 4, 6, 8 and 12 weeks. Eight parameters from gross to microscopic findings were used in order to evaluate osteoarthritic changes. Indomethacin and aspirin were chosen for the drug efficacy experiment; the two rabbits of each group were sacrificed at the end of the sixth week post-surgery. RESULTS: According to pathological findings, this operative procedure can produce osteoarthritic changes, visible both microscopically and macroscopically. There were osteoarthritic changes in the fourth week post-surgery group and, obviously, in the eighth week; these persisted until 12th weeks post-surgery. Neither indomethacin nor aspirin showed any effect in preventing osteoarthritis progression. CONCLUSIONS: Transection of the anterior cruciate and medial collateral ligament rabbit model can produce osteoarthritic lesions in the knee joint. This model can be used for further biochemical and metabolic studies.

Positive antinuclear antibody in peripheral T cell lymphoma: a case report.

The association of malignant lymphoma with positive antinuclear antibody is uncommon, and their relationship is not clear. Here a 35-year-old man is presented who initially had a high titer of antinuclear antibody; later, peripheral T cell lymphoma was found. It is suggested than an unexplained high antinuclear antibody titer may warrant searching for a malignancy.

Flow cytometric DNA and cytomorphometric analysis in renal cell carcinoma: its correlation with histopathology and prognosis.

Cell material from 49 cases of archival paraffin-embedded tumor specimens of newly diagnosed renal cell carcinoma (RCC) was studied retrospectively using rapid flow cytofluorometric (propidium iodide) DNA analysis. The degree of ploidy (DNA index), percentage of cells in the S-phase (SPF), and modal nuclear size were determined from histograms. The tumors were classified as diploid (DNA index = 0.9-1.1) or aneuploid. Proliferative activities of the tumors were assessed from the proportion of S-phase cells. The aneuploid occurrence was 77.6% in our series. Univariate and multivariate logistic regression analyses of DNA ploidy and associated parameters showed that DNA ploidy was correlated with SPF of cells (P = 0.0061) as no correlation was seen between DNA ploidy, sex, age, histological type, tumor size, stage, and nuclear size (P = 0.0697). Multiple aneuploid stem lines had no influences on ploidy and prognosis. Comparison of survival data using the multivariate stepwise hazard rate and Lee-Desu statistics showed that patient prognosis was closely related to tumor size (P = 0.006) and staging (P < 0.0001). DNA ploidy had marginal correlation to progression and disease-specific death (P = 0.064). Nevertheless, flow cytometric analysis in conjunction with conventional histopathology may have a potential role for the management of patients with RCC.

A point mutation in the chloroplast rps12 gene from Nicotiana plumbaginifolia confers streptomycin resistance.

In an effort to understand the mechanism of streptomycin resistance in Nicotiana plumbaginifolia, we have sequenced the chloroplast rps12 gene, a potential molecular target. We report that a streptomycin-resistant mutant isolated from protoplast cultures of N. plumbaginifolia contains an A-to-G transition at nucleotide position 149 in exon 2 of the chloroplast rps12 gene. The detected point mutation predicts a substitution of arginine for lysine in a phylogenetically conserved region.

Cytomorphometric and flow cytometric analysis of bladder transitional cell carcinoma using acridine orange fluorochrome: correlation with histopathology and clinical behavior.

Cell material from 79 cases of archival paraffin-embedded tumor specimens of newly diagnosed transitional cell carcinomas of the urinary bladder was studied retrospectively using rapid flow cytofluorometric DNA analysis. The male to female ratio was 62/17. The mean age at diagnosis was 65.3 +/- 10.8 years. Clinical characteristics, including survival, recurrence and progression were closely related to the histopathologic grading and tumor staging. The tumors were classified as diploid (DI = 0.9-1.1) or aneuploid. Total aneuploid occurrence was 46%. The aneuploid frequency for the various tumor grades was 25% for grade 1, 37% for grade 2 and 78% for grade 3. Stages Ta (O) and Tl (A) tumors differed from muscle-invasive tumors (T2-4) in that they had a lower frequency of aneuploid occurrence (34%, 41% vs 50%, 73%, and 75%). Multiple aneuploid stem cell lines had no influence on tumor grade or stage. The DNA ploidy was closely related to the five-year survival rate, the probability of tumor recurrence and progression. On the contrary, the modal nuclear size of the tumor cells had no correlation with histopathology or the clinical characteristics. Bladder tumors of an intermediate grade (grade 2) may be subdivided into two groups with different outcomes on the basis of flow cytometric characteristics. It is concluded that DNA flow cytometry can serve as an additional prognostic parameter for bladder cancer patients in addition to conventional histopathology.