Relationship between the expression of α-enolase in cervical carcinoma and HPV infection

目的 探讨烯醇化酶-α(α-enolase)蛋白在宫颈鳞癌中的表达及其与HPV感染的关系.方法 应用免疫组化PV-9000两步法检测30例慢性宫颈炎、61例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和70例宫颈鳞癌组织中α-enolase蛋白的表达,同时应用基因芯片技术检测70例宫颈鳞癌中HPV感染情况.结果 (1)α-enolase蛋白表达于细胞质和(或)胞核中.在慢性宫颈炎、CIN和宫颈癌中,α-enolase蛋白在胞质表达的阳性率分别为4.17%(1/24)、18.5%(10/54)和54.3%(38/70),表达依次增强(P=0.000).(2)宫颈癌中HPV总感染率为97.1%(68/70),共检出8种HPV基因型,分别为HPV16、18、58、31、52、59、66、68,构成比为80.0%、14.3%、4.3%、4.3%、2.9%、2.9%、1.43%、1.43%.双重感染10例,占14.3%.HPV16、18为主要致病基因型.(3)宫颈癌中α-enolase蛋白表达的定位与HPV16/18感染呈正相关(r=0.340,P=0.012).结论 宫颈鳞癌中α-enolase蛋白表达与HPV16/18感染密切相关,二者在宫颈鳞癌的发生过程中可能起着协同作用.     

Analysis of “task-positive” and “task-negative” functional networks during the performance of the Symbol Digit Modalities Test in patients at presentation with clinically isolated syndrome suggestive of multiple sclerosis

An abnormal pattern of brain activations has been shown in patients with multiple sclerosis during the performance of several cognitive tasks. The aim of this study is to investigate abnormalities of the patterns of activation/deactivation in the functional networks related to “task-positive” and “task-negative” events during the execution of the Symbol Digit Modalities Test (SDMT) in patients with clinically isolated syndromes (CIS) and preserved cognitive abilities. Eighteen CIS patients within 3 months from their first clinical attack and 15 healthy controls (HC) underwent neuropsychological assessment and performed an adapted functional magnetic resonance imaging (fMRI) version of the SDMT. “Task-positive” responses to task execution and “task-negative” activity of the default mode network were compared between groups. A regression analysis was performed to investigate the correlation between fMRI results and T2 lesion load (T2 LL) and brain atrophy. Neuropsychological performance did not differ between groups. Compared to HC, CIS patients exhibited an enhanced deactivation of the “task-negative” network at the level of the posterior cingulate cortex, whereas no differences between groups were found when the patterns of “task-positive” events were compared. A regression analysis detected a correlation (p < 0.001,r ranging from 0.62 to 0.73) between T2 LL and “task-positive” activations of areas that are part of the attention network, comprising the anterior cingulate gyrus, left prefrontal gyrus and inferior parietal lobe. No correlation was found between patterns of functional modifications and brain atrophy. CIS patients experience an enhanced pattern of brain deactivations during cognitive performances, which might contribute to their normal neuropsychological status.     

Epidemiology of Campylobacter jejuni isolated from patients with Guillain-Barré and Fisher syndromes in Japan

Campylobacter jejuni isolation is the standard for the diagnosis of this type of bacterial infection, but there have been no epidemiological studies of a large number of C. jejuni isolates from patients with Guillain-Barre syndrome (GBS) and Fisher syndrome (FS). For 13 years, stool specimens from GBS/FS patients have been sent from 378 hospitals throughout Japan to the Tokyo Metropolitan Institute of Public Health. A total of 113 strains (11%) were isolated from the stool specimens from 1,049 patients. The isolation rate did not differ by region. The rates were 22% for 449 patients with a history of diarrhea and 2% for the others. An additional 18 isolates were provided by various hospitals. There was no noticeable seasonal distribution in the onset of C. jejuni isolated from patients with GBS/FS. The male/female ratios were 1.7:1 for GBS and 2.2:1 for FS. The patient age range showed a peak in 10- to 30-year-old subjects who had GBS and in 10- to 20-year-old subjects who had FS. The predominance of young adults and male patients who had C. jejuni-associated GBS/FS may be related to the preponderance of young adults and male patients who had C. jejuni enteritis. The median interval from diarrhea onset to neurologic symptom onset was 10 days for GBS/FS. Penner's C. jejuni serotype HS:19 was more frequently present in GBS (67%) than in enteritis (6%) patients. HS:2 was more frequent in FS (41%) than in enteritis (14%) patients. These findings suggest that certain C. jejuni strains specifically trigger GBS and that others specifically trigger FS.     

Relationship between cytomegalovirus infection and procoagulant changes in human immunodeficiency virus‐infected patients

Cytomegalovirus is associated with hypercoagulability, and is reported to increase the risk of venous thrombosis in human immunodeficiency virus (HIV)‐infected patients. Progression to AIDS, however, is also associated with hypercoagulability and venous thrombosis, and may result in more comorbidities, such as reactivation of cytomegalovirus. It is therefore unknown whether active cytomegalovirus in HIV infection results in a procoagulant state or whether hypercoagulability is the result of HIV infection itself. In this cross‐sectional study of 104 consecutive HIV‐infected patients, active cytomegalovirus infection was associated with hypercoagulability independently of stage of HIV disease. This finding may deserve attention in preventative recommendations for use of thromboprophylaxis in HIV‐infected patients.     

Genetic characterization of adenovirus strains isolated from patients with acute conjunctivitis in the city of São Paulo, Brazil

Genome analysis was carried out on adenovirus strains isolated from patients with acute follicular conjunctivitis in the city of S?o Paulo, Brazil. Eighteen conjunctival scrapings, collected between December 1993 and March 1994, were analyzed by two methods: a combination of polymerase chain reaction with restriction fragment length polymorphism and viral DNA restriction analysis, carried out using 10 restriction endonucleases: BamHI, BglI, BglII, HindIII, KpnI, SacI, SalI, SmaI, XbaI, and XhoI. Among 11 adenovirus detected by cell culture isolation, nine were Ad8, and two were Ad7. By restriction analysis the Ad8 isolates were typed as two new variants-Ad8/D11 (seven of nine samples) and Ad8/D12 (two of nine samples). Ad7 isolates were identified as a subtype of the widespread genome type Ad7b and the virulent type Ad7h, a predominant genome type circulating in Argentina, Chile, and Uruguay but absent in Brazil until 1991.     

Naming ability in patients with mild to moderate Alzheimer's disease: what changes occur with the evolution of the disease?

OBJECTIVES:

Naming deficit is a linguistic symptom that appears in the initial phase of Alzheimer''s disease, but the types of naming errors and the ways in which this deficit changes over the course of the disease are unclear. We analyzed the performance of patients with Alzheimer''s disease on naming tasks during the mild and moderate phases and verified how this linguistic skill deteriorates over the course of the disease.

METHODS:

A reduced version of the Boston Naming Test was administered to 30 patients with mild Alzheimer''s disease, 30 patients with moderate Alzheimer''s disease and 30 healthy controls. Errors were classified as verbal semantic paraphasia, verbal phonemic paraphasia, no response (pure anomia), circumlocution, unrelated verbal paraphasia, visual errors or intrusion errors.

RESULTS:

The patients with moderate Alzheimer''s disease had significantly fewer correct answers than did both the control group and the group with mild Alzheimer''s disease. With regard to the pattern of errors, verbal semantic paraphasia errors were the most frequent errors in all three groups. Additionally, as the disease severity increased, there was an increase in the number of no-response errors (pure anomia). The group with moderate Alzheimer''s disease demonstrated a greater incidence of visual errors and unrelated verbal paraphasias compared with the other two groups and presented a more variable pattern of errors.

CONCLUSIONS:

Performance on nominative tasks worsened as the disease progressed in terms of both the quantity and the type of errors encountered. This result reflects impairment at different levels of linguistic processing.     

Defective expression of Gα12 in the testes of azoospermia patients and in the spermatozoa with low motility

Antibody to the Gα12-subunit of guanine nucleotide regulatory proteins was used to determine whether the Gα12 is present in adult human spermatogenic cells and to determine its role in dyszoospermia. Immunoblots from testes and spermatozoa demonstrated the presence of Gα12 in the samples. Immunohistochemical analyses of testes found that Gα12 was expressed in the cytoplasm of Leydig cells and was expressed in spermatids from the elongating Sb phase to mature sperm. Indirect immunofluorescence of human spermatozoa revealed the presence of Gα12 in the neck region and the midpiece of the sperm. Gα12 in spermatids and spermatozoa partially co-localized with F-actin and α-tubulin. Immunohistochemical analyses of tissues from three patients with non-obstructive azoospermia showed abnormal expression of Gα12 in more than 45% of spermatids. Furthermore, Western blots and indirect immunofluorescence found defective expression of Gα12 in low-motility spermatozoa with midpieces that were bent on themselves. Therefore, it suggests that Gα12 plays a role in polarity and tail formation as spermatids mature. Furthermore, Gα12 may be a candidate protein responsible for azoospermia caused by spermatogenic disturbance or midpiece deformities.     

MALDI-TOF MS identification of Malassezia species isolated from patients with pityriasis versicolor at the seafarers’ medical service in Dakar,Senegal

Pityriasis versicolor (PV) is a superficial mycosis caused by yeast of the genus Malassezia. The most common isolated Malassezia species in PV lesions differ among M. furfur, M. globosa and M. sympodialis. We purpose to determine the distribution of Malassezia species in PV patients at the seafarers’ medical service in Dakar, Senegal and to examine whether any association between identified Malassezia species and patients’ profile. From May 2017 to August 2017, first a questionnaire was filled to get informative data before collection of skin scrapings taken from most scaly site using sterile scalpel blade and application of scotch^® for direct examination (DE). At the laboratory, DE, culture and identification by MALDI-TOF MS were done. One hundred patients with PV – all men – were included with a mean age of 34 years. Among seafarers, 81% were sailors. Clinical prevalence of PV was highest in aged adults patients with ages of 31 to 60 years (56%). Seafarers with high level of education were less representative with only 2%. The mean duration of the PV was 26.83 months. 20% of subjects suffered lesions in more than one location. The chest was the most affected anatomical site. Furthermore, possible predisposing factors associated with PV were also detected. DE was positive in 95% but culture growth only in 46%. MALDI-TOF MS analysis of the positive cultures could be performed in 84.8% (39/46). Only M. furfur was identified in 100% (39/39). In definitive, M. furfur is the only causative agent of PV in Dakar.     

Are there systemic changes in the arterial biomechanics of intracranial aneurysm patients?

Current theories on the development of intracranial aneurysm suggest that there is a general weakness of vascular connective tissue. Potential systemic alterations in arterial wall biomechanics were tested in the present study. A three-dimensional in vitro stress-strain analysis was made in the 0-200-0 mmHg pressure range on cylindrical segments excised from the anterior cerebral artery, the radial artery and from the arteria dorsalis pedis of aneurysm patients and of control cadavers. In the anterior cerebral artery from aneurysm patients (intracranial artery segments directly not affected by the aneurysm or by the subarachnoid bleeding), we found the wall thickness to be larger (0.1480+/-.019 versus 0.091+/-0.004 mm), the radius/wall thickness ratio smaller (9.7+/-1.4 versus 14.1+/-1.2), and the tangential wall stress lower [(0.122+/-0.019)x10(6) versus (0.181+/-0.016)x10(6) N/m2 at 100 mmHg] than in control subjects. Reduced radius was found in the extremity arteries studied. Elastic parameters, as incremental distensibility and elastic modulus, were remarkable similar. Our study demonstrates changes in the geometry of walls of arteries not directly affected by aneurysm formation, and it thus confirms systemic vascular pathology in this disease. At the same time, these data show that the molecular and morphological defects of arterial connective tissue formation generally thought to induce intracranial aneurysms will probably not affect the components responsible for the passive elastic properties of the vascular wall.     

Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls

Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1‐like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL‐18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL‐18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American‐European classification criteria. IL‐18 and TGF‐β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL‐18 were related (R = 0·52, P = 0·0005). No relation was found neither between IL‐18 versus IgG2, IgG3 or IgA, nor between serum TGF‐β1 versus any of the immunoglobulins. Since serum levels of IL‐18 are related to serum IgG1, IL‐18 may be of importance for IgG1 switch and/or release.     

Bilateral changes of TNF-α and IL-10 protein in the lumbar and cervical dorsal root ganglia following a unilateral chronic constriction injury of the sciatic nerve

Background  

There is a growing body of evidence that unilateral nerve injury induces bilateral response, the mechanism of which is not exactly known. Because cytokines act as crucial signaling molecules for response of peripheral nerves to injury, they may be induced to mediate the reaction in remote structures.     

Improvements in population-based survival of patients presenting with metastatic rectal cancer in the south of the Netherlands, 1992–2008

We analysed population-based treatment and survival data of patients who presented with metastatic rectal cancer. All patients diagnosed with primary synchronous metastatic rectal cancer between 1992 and 2008 in the Eindhoven Cancer Registry area were included. Date of diagnosis was divided into three periods (1992–1999, 2000–2004, 2005–2008) according to the availability of chemotherapy type. We assessed treatment patterns and overall survival according to period of diagnosis. The proportion of patients diagnosed with stage IV disease increased from 16% in 1992–1999 to 20% in 2005–2008 (P < 0.0001). Chemotherapy use increased from 5% in 1992 to 61% in 2008 (P < 0.0001). Resection rates of the primary tumour decreased from 65% in 1992 to 27% in 2008 (P < 0.0001), while metastasectomy rates remained constant since 1999 (9%). Median survival increased from 38 weeks (95% confidence interval (CI) 32–44) in 1992–1999 to 53 weeks (95% CI 48–61) in 2005–2008. Among patients not receiving chemotherapy median survival remained approximately 30 weeks. Multivariable analysis confirmed the lower risk of death among patients diagnosed in more recent years. Increased use of chemotherapy went together with improved median survival among patients with metastatic rectal cancer in the last two decades. Stage migration as an effect of more effective imaging procedures is likely to be partly responsible for this improved survival.     

Modulation of immunity in mice with latent toxoplasmosis—the experimental support for the immunosuppression hypothesis of Toxoplasma-induced changes in reproduction of mice and humans

The immunosuppression hypothesis suggests that the increased sex ratio in mice and women with latent toxoplasmosis, retarded embryonic growth in the early phases of pregnancy, prolonged pregnancy of Toxoplasma-infected women, and increased prevalence of toxoplasmosis in mothers of children with Down syndrome can be explained by the presumed immunosuppressive effects of latent toxoplasmosis. Here, we searched for indices of immunosuppression in mice experimentally infected with Toxoplasma gondii. Our results showed that mice in the early phase of latent infection exhibited temporarily increased production of interleukin (IL)-12 and decreased production of IL-10. In accordance with the immunosuppression hypothesis, the mice showed decreased production of IL-2 and nitric oxide and decreased proliferation reaction (synthesis of DNA) in the mixed lymphocyte culture in the early and also in the late phases of latent toxoplasmosis. Since about 30% of the world population are latently infected by T. gondii, the toxoplasmosis-associated immunosuppression might have serious public health consequences.     

IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease

Th1 lymphocytes are crucial in the immune response against Mycobacterium tuberculosis. Nevertheless, IFN-γ alone is not sufficient in the complete eradication of the bacteria, suggesting that other cytokines might be required for pathogen removal. Th17 cells have been associated with M. tuberculosis infection, but the role of IL-17-producing cells in human TB remains to be understood. Therefore, we investigated the induction and regulation of IFN-γ and IL-17 during the active disease. TB patients were classified as High and Low Responder individuals according to their T cell responses against the antigen, and cytokine expression upon M. tuberculosis stimulation was investigated in peripheral blood and pleural fluid. Afterwards, the potential correlation among the proportions of cytokine-producing cells and clinical parameters was analyzed. In TB patients, M. tuberculosis induced IFN-γ and IL-17, but in comparison with BCG-vaccinated healthy donors, IFN-γ results were reduced significantly, and IL-17 was markedly augmented. Moreover, the main source of IL-17 was represented by CD4(+)IFN-γ(+)IL-17(+) lymphocytes, a Th1/Th17 subset regulated by IFN-γ. Interestingly, the ratio of antigen-expanded CD4(+)IFN-γ(+)IL-17(+) lymphocytes, in peripheral blood and pleural fluid from TB patients, was correlated directly with clinical parameters associated with disease severity. Indeed, the highest proportion of CD4(+)IFN-γ(+)IL-17(+) cells was detected in Low Responder TB patients, individuals displaying severe pulmonary lesions, and longest length of disease evolution. Taken together, the present findings suggest that analysis of the expansion of CD4(+)IFN-γ(+)IL-17(+) T lymphocytes in peripheral blood of TB patients might be used as an indicator of the clinical outcome in active TB.