Association between HLA-DRB1 alleles and tuberculosis: a meta-analysis.

Although a number of studies have reported that human leukocyte antigen (HLA)-DRB1 alleles may be correlated with tuberculosis (TB), most were based on small samples or inconsistent and unclear results. Here, we present a meta-analysis to investigate the relationship between HLA-DRB1 alleles and TB susceptibility. We gathered relevant information from published studies on the association between HLA­DRB1 alleles and TB susceptibility through a systematic research. Data from eligible fifteen studies were included in the meta-analyses. Each dataset was statistically analyzed to evaluate the HLA­DRB1 alleles by calculating the respective odds ratios (ORs) and 95% confidence intervals (CIs). The results revealed that frequencies of two DRB1 alleles were significantly decreased in TB: DRB1*03 (P = 0.016, OR = 0.78, 95%CI = 0.67­0.95) and DRB1*07 (P = 0.017, OR = 0.81, 95%CI = 0.68­0.96). Thus, our data indicate that DRB1*03 and DRB1*07 may provide protective effects against TB susceptibility. However, well­designed studies with large sample sizes are required for better understanding of this association.

Molecular identity of ramie germplasms using simple sequence repeat markers.

DNA identity is highly effective and efficient for distinguishing crop varieties regardless of their phenotypic similarities. To establish DNA identity in ramie, 21 simple sequence repeat primers were amplified in 108 accessions of domestic and exotic ramie germplasms. Sixty polymorphic bands were obtained, with an average of 2.9 bands per locus and 2-8 band types per primer locus (average of 5.19 band types). The Simpson's diversity index of the 21 simple sequence repeat loci ranged from 0.158 to 0.808 with an average of 0.612. There was large difference in the specific index in the germplasm tested, from 44.082 to 218.163, with an average of 83.620. Based on allele band type, 8 primer pairs were selected for DNA fingerprinting of the 108 genotypes. The combination of the 8 primer pairs were found to be very effective for distinguishing these genotypes, indicating that they can be used in the molecular DNA identity of ramie.

A variant within intron 1 of the PTPN22 gene decreases the genetic susceptibility of ankylosing spondylitis in a central south Chinese Han population.

OBJECTIVES: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) is generally accepted as a key factor in maintaining immune cellular homeostasis. So far, no association has been reported between the polymorphisms of PTPN22 and ankylosing spondylitis (AS) in Chinese populations. We attempted to explore the association between the PTPN22 gene and AS in a central south Chinese Han population. METHOD: Our study involved 180 HLA-B27(+) unrelated patients and 360 HLA-B27(-) healthy individuals. Seven single nucleotide polymorphisms (SNPs: rs2476601, rs1217414, rs1217418, rs1746853, rs1970559, rs3765598, and rs3811021) were detected. Genotyping was conducted using the polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. RESULTS: rs2476601 was not polymorphic enough in both patients and controls. The SNP rs1217414 was found to be associated with AS but the other five of the seven selected SNPs (rs1217418, rs1746853, rs1970559, rs3765598 and rs3811021) were not. CONCLUSIONS: The PTPN22 gene might be associated with AS in a central south Chinese Han population.

Association of IL-4 promoter polymorphisms with asthma: a meta-analysis.

This study aimed to more precisely assess the correlation between interleukin-4 (IL-4) promoter polymorphisms and the susceptibility risk of asthma. We conducted association studies on IL-4 promoter C-33T, C-589T, and G-1098T polymorphisms with asthma using data obtained from MEDLINE up to September 2011. Results showed that the polymorphisms IL-4 C-33T and C-589T were significantly associated with asthma; however, significant associations were found only in the European population. In addition, the TT+CT genotype was significantly associated with asthma in adults and no significant association was found in asthma status subgroup analyses. This meta-analysis showed that IL-4 C-589T and C-33T were associated with asthma in Europeans. To further confirm correlations between polymorphisms of the IL-4 promoter with asthma susceptibility, studies involving a larger number of patients worldwide are necessary.

Clinical relevance and functional implications for human leucocyte antigen-g expression in non-small-cell lung cancer.

HLA-G has been documented both in establishment of anti-tumour immune responses and in tumour evasion. To investigate the clinical relevance of HLA-G in non-small-cell lung cancer (NSCLC), expression status and potential significance of HLA-G in NSCLC were analysed. In this study, HLA-G expression in 101 NSCLC primary lesions and plasma soluble HLA-G (sHLA-G) from 91 patients were analysed with immunohistochemistry and ELISA, respectively. Correlations between HLA-G status and various clinical parameters including survival time were evaluated. Meanwhile, functional analysis of transfected cell surface HLA-G expression and plasma sHLA-G form NSCLC patients on natural killer (NK) cell cytolysis were performed. Data revealed that HLA-G was expressed in 41.6% (42/101) NSCLC primary lesions, while undetectable in adjacent normal lung tissues. HLA-G expression in NSCLC lesions was strongly correlated to disease stages (P= 0.002). Plasma sHLA-G from NSCLC patients was markedly higher than that in normal controls (P= 0.004), which was significantly associated with the disease stages (I versus IV, P= 0.025; II versus IV, P= 0.029). Patient plasma sHLA-G level (≥median, 32.0 U/ml) had a significantly shorter survival time (P= 0.044); however, no similar significance was observed for the lesion HLA-G expression. In vitro data showed that both cell surface HLA-G and patient plasma sHLA-G could dramatically decrease the NK cell cytolysis. Our findings indicated that both lesion HLA-G expression and plasma sHLA-G in NSCLC is related to the disease stage and can exert immunosuppression to the NK cell cytolysis, indicating that HLA-G could be a potential therapeutic target. Moreover, plasma sHLA-G in NSCLC patients could be used as a prognosis factor for NSCLC.

Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax.

Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé syndrome caused by folliculin gene (FLCN) mutation, which is also found in isolated familial PSP cases. A complete genetic analysis of FLCN was performed in 102 unrelated Chinese patients with isolated PSP and 21 of their family members. Three novel mutations (c.924_926del, c.1611_1631del and c.1740C>T) and a previously reported mutation (c.1733insC) were identified in five familial and five sporadic PSP patients. Of the 21 family members of patients with PSP including 3 previous considered as sporadic, 4 (19%) had history of at least one episode of PSP and 9 (43%) were FLCN mutant carriers without PSP. Seven of the nine (78%) mutant carriers had pulmonary cysts detected by high-resolution computed tomography (HRCT). Although c.924_926del and c.1611_1631del were found in eight patients from the same geographic district, haplotype analysis demonstrated that they did not share the same affected haplotype, thus excluding common ancestry. This study first demonstrates that FLCN mutation contributes to not only familial but also 'apparently sporadic' patients with isolated PSP. It suggests that mutation analysis and HRCT scan may be recommended for first-degree family members of PSP patients with FLCN mutations, irrespective of their family history status of PSP.

Leiomyosarcoma in the nasopharynx: MR imaging findings.

The MR imaging findings of a leiomyosarcoma arising from the nasopharynx are presented. To our knowledge, this is the first MR imaging description of this entity.

Mucopolysaccharidosis I under enzyme replacement therapy with laronidase--a mortality case with autopsy report.

There is little information about MPS I-related complications during laronidase therapy. We describe the first autopsy report of a young male MPS I patient who died of infection-induced cardiopulmonary failure following 2 years of weekly treatment with laronidase.

Abnormality of the DNA double-strand-break checkpoint/repair genes, ATM, BRCA1 and TP53, in breast cancer is related to tumour grade.

The role of the DNA double-strand-break (DSB) checkpoint/repair genes, ATM, BRCA1 and TP53, in sporadic breast cancer requires clarification, since ATM and BRCA1 mutations are rare in sporadic tumours. In an attempt to explain this phenomenon, we postulated that (i) in addition to genetic deletion, abnormal expression of DSB checkpoint/repair proteins might abolish the function of these genes and (ii) there might be a combined effect of individual defective genes during breast cancer pathogenesis. Using a largely homogenous group of 74 specimens of early-onset (< or =35 years of age) infiltrating ductal carcinomas, we examined associations between pathological grade and genetic deletion and/or abnormal protein expression of ATM, BRCA1 and TP53. The results showed that high-grade tumours displayed a high frequency of loss of heterozygosity (LOH) at, and/or abnormal expression of, ATM, BRCA1 and TP53. Multigenetic analysis showed abnormalities in BRCA1 to be independently associated with high-grade tumours. ATM and TP53 appeared to play an assistant role, abnormalities in these genes significantly increasing the possibility of poor differentiation in tumours with abnormalities in BRCA1. Furthermore, a higher number of abnormalities (LOH or abnormal expression) in these three genes correlated with poor tumour differentiation. Thus, this study suggests that combined changes in several DSB checkpoint/repair genes belonging to a common functional pathway are associated with breast cancer pathogenesis.

Tubulointerstitial nephritis associated with a novel mitochondrial point mutation.

BACKGROUND: Nephropathy caused by mitochondrial disorders is a relatively newly recognized disease. Only a few cases have been reported in the literature, and most of them are proximal tubulopathy-presenting Fanconi syndrome. Here we report on a novel mutation in two familial cases of tubulointerstitial nephropathy associated with concentrating defect. METHODS: Renal biopsy specimens were examined by light microscopy and electron microscopy. Mitochondrial genomic DNA isolated from renal biopsy specimens was amplified by polymerase chain reaction (PCR) and sequenced in its entirety. The DNA sequences were analyzed by (1) comparing with the Anderson et al's mitochondrial sequences; (2) comparing with DNA sequences obtained from 97 human controls, including both healthy individuals and patients with renal diseases; and (3) comparing with the counterparts in 90 different species. RESULTS: Dismorphic mitochondria with occasional intramitochondrial inclusions were found in the renal tubular epithelial cells. A novel mitochondrial point mutation was identified at the position 608, that is, the distal end of the anticodon stem of the tRNA(Phe) molecule. The A to G substitution at this position was not observed in 97 human controls and was found to be highly conserved in evolution. CONCLUSIONS: We have identified an A608G mutation of mitochondrial genome in two cases whose presentation include tubulointerstitial nephritis and stroke.

Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?

HYPOTHESIS: Mutant p53 gene has lost its tumor suppression function and is considered to be a very important step in hepatocellular carcinoma development. We propose that the mutant p53 gene plays a role in its invasiveness and prognosis after resection. DESIGN: A case-controlled study. SETTING: A referral center. PATIENTS: Seventy-nine consecutive patients who underwent surgical resection for hepatocellular carcinoma entered this study. INTERVENTION: Tissue sections of resected hepatocellular carcinoma (deparaffinized and rehydrated from formalin-fixed and paraffin-embedded sections) were incubated with antihuman p53 monoclonal antibody and immunostained. The p53 result was scored without prior knowledge of the patients' status. A 10% immunopositivity was regarded as the threshold value. MAIN OUTCOME MEASURE: The immunopositive rate of p53 was 69.6% (55 of 79 patients). The clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum alpha-fetoprotein, and Child-Pugh class); the histological variables (size, capsule, vascular permeation; grade of differentiation, and multinodularity); and postoperative course (recurrence, tumor-free interval, death, and survival period) were correlated with p53 immunopositivity. RESULTS: From univariate analysis, more patients with p53 positivity were male (92.7 vs 0%) (P<.001); had vascular permeation (80% vs 50%) (P =.007) (odds ratio [OR], 4.0); no complete capsule (83.6% vs 62.5%) (P =.04) (OR, 3.1); and daughter nodules (90.9% vs 70.8%) (P =.04) (OR, 4.1) than patients with negative p53 staining. From multivariate analysis, only sex and vascular permeation remained significant (P =.001 and P =.008, respectively). Although more patients with p53 positivity had tumor recurrence (78% vs 50%) (P =.01) and death (64% vs 33%) (P =. 01), the Cox proportional hazards model showed that p53 overexpression had only weak correlations with tumor-free interval and survival time (P =.09 and P =.08, respectively). CONCLUSIONS: Our results show that the biological behavior of the mutant p53 gene is strongly related to the invasiveness of hepatocellular carcinoma and may also influence the postoperative course. We suggest that the immunopositivity of the mutant p53 gene has a predictive role in the prognosis of patients with resected hepatocellular carcinoma.

Segmental dilatation of the ileum as an unusual cause of gastrointestinal bleeding: report of one case.

We report a case of segmental dilatation of the ileum in a 10-month-old male infant. Intermittent loose black-colored stool passage and normocytic anemia were noted at the initial visits to our hospital. There was no symptom or sign of intestinal obstruction such as abdominal distention or vomiting. On physical examination, he was found to be pale but his abdomen was soft and flat. Digital examination revealed brownish stool tinged with black-colored oil-like stool but no polyp. Laboratory studies excluded coagulopathy, hemolytic anemia and lead poisoning. During hospitalization, he was treated with nothing per mouth, intravascular fluids, ranitidine, and transfusion of packed red blood cells. All examinations including panendoscopy, Technetium-99m (99mTc)-pertechnetate Meckel's diverticulum scan, and double contrast colon series revealed no organic lesion except that 99mTc-red blood cell bleeding scans showed abnormal bleeding in the small intestine. Because of his persistent gastrointestinal bleeding with unknown cause, we did an exploratory laparotomy when the patient was 13 months old and idiopathic segmental dilatation of the ileum was confirmed. The dilated segment is supposed to be idiopathic because of histologically proven normal muscle layers without ectopic tissue. This case suggests that segmental dilatation of the ileum can only present as gastrointestinal bleeding without intestinal obstruction.

Adenoid basal carcinomas of the cervix: a unique morphological evolution with cell cycle correlates.

Adenoid basal carcinoma (ABC) is a rare cervical carcinoma of postmenopausal women composed of small basal-type (basaloid) cells with focal endocervical ("adenoid") differentiation. ABCs are associated with high-grade squamous intraepithelial lesions (HSIL) and contain integrated human papillomavirus type 16 DNA. However, ABCs have a favorable prognosis and do not metastasize. Five (5) ABCs were analyzed histologically for a marker distinguishing basal/ squamous from columnar (adenoid) differentiation (p63) and cell cycle activity (Ki-67), and compared with 20 cervical (CC) carcinomas. In contrast to other CCs, ABCs contained 4 distinct components, including (1) a classic HSIL; (2) a limited invasive component with squamoid maturation, often with a discrete layer of peripheral basal cells; (3) outgrowth of small basal cells from either HSIL or squamoid areas; (4) focal endocervical (adenoid) differentiation. ABCs showed distinct differences in cell cycle activity relative to CCs. Ki-67 positivity was high in associated HSILs but remained high and concentrated in the suprabasal cells of the invasive squamoid component of ABC. Moreover, proliferative index was variable to sharply reduced in areas of basaloid and adenoid differentiation, in contrast to conventional CCs. ABC is a unique neoplasm, not only by its transition through multiple phenotypes during invasion, but also by a proliferative index that is high in more mature neoplastic cells during the infiltrative process and reduced with progressive basal differentiation. The precise mechanism underlying this unique process of tumor evolution is unclear. However, the postmenopausal status of these patients suggests that host factors related to aging may influence tumor evolution and morphology after HPV 16 infection.

Activity of p44/42 MAP kinase in the caudal subnucleus of trigeminal spinal nucleus is increased following perioral noxious stimulation in the mouse.

The extracellular signal-regulated protein kinase-1 and -2 (ERK1 and ERK2), also referred to as the p44/42 mitogen-activated protein kinase (p44/42 MAP kinase), plays an essential role in neuronal signal transduction, but its function involved in nociceptive response has not been deeply studied yet. Here we report immunohistochemical evidence that p44/42 MAPK might be critical in nociceptive response. We found that after formalin was injected into the perioral skin of the upper lip of mice, the number of activated p44/42 MAPK-like immunoreactive neurons was significantly increased in the laminae I and II of the caudal subnucleus of the trigeminal spinal nucleus (Sp5C). The positive neurons and fibers were mostly concentrated in the middle portion of Sp5C dorsoventrally, where the afferent fibers innervating the skin of the upper lip are terminated. The reactive products were localized in perikarya, dendrites, nuclei, and diffusely in the neuropil. The present result suggests that p44/42 MAPK may be important in the transmission and modulation of noxious information in Sp5C.

Glycogen storage disease type IV: a case report.

Glycogen storage disease type IV (GSD-IV) is a rare autosomal recessive disease caused by a deficiency of glycogen branching enzyme (GBE) activity. This results in the accumulation of abnormal glycogen in the liver and other organs. We report the case of a 14-month-old female patient with typical hepatic pathologic findings of GSD-IV. The patient suffered from decreased muscle tone and progressive hepatosplenomegaly since birth. A wedge biopsy of the liver showed enlarged hepatocytes with colorless to faintly eosinophilic ground glass intracytoplasmic inclusions. Portal fibrosis and lobular, fibrous septa were present. Ultrastructure of the inclusions revealed non-membrane-bound fibrillar material 5 nm in maximal diameter. Enzyme study revealed a total deficiency of GBE activity.

The effect of tetrandrine and extracts of Centella asiatica on acute radiation dermatitis in rats.

Radiation injury to the skin is one of the major limiting factors in radiotherapy. We designed this study using Sprague-Dawley rats to evaluate the reduction in skin injury achieved using natural products from plant extracts as protection. The acute skin reaction in tetrandrine- and Madecassol-treated animals appeared earlier, but was significantly less severe, than in the control group. The peak skin reactions in the tetrandrine group were less serious than those of the control group at three different radiation doses. At a high dose irradiation, the healing effect of tetrandrine is better than Madecassol and vaseline. The histologic findings indicate that tetrandrine and Madecassol are able to reduce acute radiation reactions by their anti-inflammatory activity.

Gastro-intestinal bleeding caused by leiomyoma of the small intestine in a child with neurofibromatosis.

UNLABELLED: Gastro-intestinal bleeding is an uncommon presentation in children with neurofibromatosis. Gastro-intestinal involvement caused by jejunal leiomyoma has only been described in adults. To the best of our knowledge, this is the first paediatric case of jejunal leiomyoma associated with neurofibromatosis. We present a 10-year-old girl with a 9-month history of anaemia and low gastro-intestinal bleeding. Abdominal sonography and small bowel series showed a submucosal mass in the proximal jejunum. On surgery, a submucosal tumour was excised and histological examination suggested a diagnosis of "smooth muscle tumour of undetermined malignant potential". There were no recurrence of symptoms for 4 years after the operation. CONCLUSION: Jejunal leiomyoma should be considered in a child with neurofibromatosis presenting with gastro-intestinal bleeding.

Detection of PAX3-FKHR and PAX7-FKHR fusion transcripts in rhabdomyosarcoma by reverse transcriptase-polymerase chain reaction using paraffin-embedded tissue.

BACKGROUND: Alveolar rhabdomyosarcoma (RMS) is associated with a characteristic chromosomal translocation t(2;13)(q35;q14). The genes involved in this translocation are paired box (PAX)3 on chromosome 2 and forkhead in RMS (FKHR) on chromosome 13. An occasional variant translocation t(1;13)(p36;q14) affecting PAX7 and FKHR on chromosomes 1 and 13, respectively, has also been described. Chromosomal translocations in RMS are detected using conventional cytogenetic analysis, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) on fresh or frozen tissue samples. We describe the results of RT-PCR analysis of PAX3-FKHR and PAX7-FKHR chimeric messages in formalin-fixed, paraffin-embedded tissue samples from 17 RMS cases. METHODS: RNA was extracted from formalin-fixed, paraffin-embedded RMS tissue. Oligonucleotide primers corresponding to the regions of PAX3, PAX7 and FKHR were used for the detection of PAX3-FKHR and PAX7-FKHR chimeric messages. A seminested PCR of the PCR products was used to increase the sensitivity of detection. The amplified fragments were purified and directly sequenced to confirm the specificity of the methods. RESULTS: The PAX3-FKHR chimeric message was detected in all three cases of alveolar RMS but not in any of the 12 embryonal and two pleomorphic RMS cases. The PAX7-FKHR fusion transcript was detected in one case of embryonal RMS. CONCLUSIONS: The results indicate that the RT-PCR assay is a reliable method for the detection of the PAX3-FKHR fusion transcript of alveolar RMS in formalin-fixed, paraffin-embedded tissue. This simple method enables pathologists to identify chromosomal rearrangements in RMS as a diagnostic aid in cases where fresh or frozen tissue is not available.