Plasma Cytokines Profile in Patients with Parkinson’s Disease Associated with Mutations in GBA Gene

Bulletin of Experimental Biology and Medicine - Plasma cytokine concentration in patients with Parkinson’s disease and mutation in GBA gene, in patients with sporadic Parkinson’s...     

Hormonal changes in patients with mumps orchitis

目的：检测不同年龄感染腮腺炎性睾丸炎患者的激素水平改变。方法：应用放射免疫法测定３组患者的ＦＳＨ、ＬＨ、催乳素、雌二醇和睾酮水平。结果：３组患者均存在不同程度的激素紊乱，尤其以青春期发生感染的组Ⅱ有显著激素水平改变。与对照组比较，组Ⅱ的ＦＳＨ、ＬＨ、催乳素和雌二醇分别升高２８７、１９７、１８１和１９８倍，睾酮减少６４１倍。结论：感染腮腺炎性睾丸炎患者的生殖激素有明显改变，且与感染时患者的年龄有关。     

Clinical Experience with Growth Hormone Treatment in Patients with β-Thalassaemia Major

The aetiology of the growth retardation occurring in patients with beta-thalassaemia major is considered to be multifactorial. Although growth hormone (GH) secretion appears to be normal in many thalassaemic patients with short stature, there is evidence indicating impaired GH secretion in approximately 3% of patients. The response to recombinant human GH treatment (rHGH) is not predictable, based on either the parameters known to affect the response to treatment or the type of defect in the GH-insulin-like growth factor (IGF-1) axis. The wide variation in growth velocity observed during rHGH treatment suggests that treatment with the usual dose of rHGH (0.6 U/kg/week) cannot be considered effective in all patients, although rHGH has been successful in some patients. Therefore further studies are required in order to evaluate the effects of supraphysiological doses of rHGH on growth. Since these patients are prone to develop abnormal glucose homeostasis, oral glucose tolerance tests must be performed periodically during rHGH treatment.     

Induction of cytotoxic T lymphocyte respones in vivo after immunotherapy with dendritic cells in patients with nasopharyngeal carcinoma

The aim of the present study was to determine the efficacy of immunotherapy with dendritic cells to elicit EBV-specific CTL-immunity in advanced cases of EBV-positive patients with nasopharyngeal carcinoma (NPC) and to determine the safety and toxicity of this preparation. Nine cases of histologically confirmed patients with NPC undergoing treatment with radiological therapy were enrolled in this study. Dendritic cells, generated in vitro from blood monocytes of patients were cultured and matured with cytokines and then infected with recombinant adenovirus vaccine containing EBV-latent membrane protein-2 (Ad-LMP2). On 9 days' cultivation of cells, the matured DCs were harvested, irradiated with Co and then injected intradermally to patients with NPC. The injections were performed 3 times totally. After immunization, the CTL responses were assayed by means of cytotoxicity and epitope-specific IFN-γproduction. The results of this trial showed that all patients could tolerate this kind of treatment without any side effect, during which marked increase of LMP2-specific CTL-responses could be demonstrated in 5 patients of this group. And the level of IgA/VCA antibody decreased in 8 of 9 patients, thus accounting for a better prognosis for these patients. All patients will be followed up for another one year. At least, the present work shows that intradermal vaccination with autologous DCs infected with recombinant Ad-LMP2 adenovirus is a safe procedure in NPC patients, in which this procedure can enhance the LMP2-specific CTL responses in patients. These data are encouraging to develop more effective vaccine strategies for the treatment of nasopharyngeal carcinoma.     

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

Two common chronic childhood diseases-celiac disease (CD) and type 1 diabetes (T1D)-result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions.     

Loss-of-function mutations in cathepsin C in two families with Papillon-Lefèvre syndrome are associated with deficiency of serine proteinases in PMNs

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disease that involves severe periodontitis and hyperkeratosis of the hand palms and foot soles. Recently it was found that PLS patients carry loss-of-function mutations in the gene encoding cathepsin C (CTSC). In the present study we have analyzed the CTSC gene in two unrelated families with PLS. In the first non-consanguineous family, mutation analysis revealed the previously reported c.815G>C/p.R272P mutation. The second consanguineous family displayed a c.1213C>A mutation which resulted in the novel mutation p.H405N and is the first mutation described in the active site of the enzyme. The PLS patients had, next to the absence of cathepsin C activity in polymorphonuclear leukocytes (PMNs), no activity of the three serine proteinases elastase, cathepsin G and proteinase 3. Serine proteinases are supposed to be important in both the innate and adaptive immune systems. Their absence in PLS patients could explain the inadequate defense to periodontal infection.     

Correlation of clinical outcomes with β-glucan levels in patients with invasive candidiasis

The correlation of β-glucan (BG) levels with clinical outcomes in invasive candidiasis (IC) remains unknown. Patients with proven IC were followed prospectively from diagnosis to outcome with twice-weekly serum BG sampling. Correlation of BG with clinical outcome was assessed in each patient. BG levels tend to decrease in successfully treated patients and increase in treatment failures. BG levels may be useful as surrogates for outcome evaluation of IC.     

Changes of immunoreactivity in α1-antitrypsin in patients with autoimmune diseases

Recent studies from this laboratory have shown that a monoclonal antibody prepared against a specific epitope on ₁-antitrypsin is a valuable diagnostic marker for autoimmune conditions. In the present study we have further characterized this monoclonal antibody and reassessed its diagnostic value in screening samples from patients with various autoimmune conditions. ₁-Antitrypsin was micropurified from patients with selected autoimmune conditions and from normal donors. The purified ₁-antitrypsin isolated. from patients with autoimmune conditions and normal donors was deglycosylated losing both a mixture of exoglycosidases and endoglycosidase F. The immunoreactivity of the native and deglycosylated ₁-antitrypsin was examined using both a monoclonal antibody and a polyclonal antibody in enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), respectively. It was noted that ₁-antitrypsin isolated from patients with autoimmune diseases generated a displacement curve dissimilar to ₁-antitrypsin purified from normal donors or ₁ antitrypsin from patients with autoimmune diseases subjected to deglycosylation when these samples were examined by ELISA using the monoclonal antibody. However, when the polyclonal antibody was used for these studies, no difference was found between the native and deglycosylated ga₁,-antitrypsin suggesting that the monoclonal antibody recognized an epitope not detectable by the polyclonal antibody. We have also assessed the diagnostic usefulness of this monoclonal antibody using a battery of 530 serum samples obtained from patients with different autoimmune diseases and compared to normal human serum (NHS,N–66); these include: systemic lupus erythematosus (SLE,N=149), rheumatoid arthritis (RA,N=64), renal diseases (NP,N=33), liver diseases (HP,N=33), mixed connective tissue disease (MCTD,N = 12), diabetes (DB,N=40), SjÖgren's syndrome (SS,N = 41), polymyositis (PM,N=20), scleroderma (SCL,N=20), Alzheimer's disease (AZ,N=11), and patients with elevated levels of carcinoembryonic antigen (CEA,N=41). The results of this study demonstrated that this monoclonal antibody is positively correlated with SLE and SS. The significance of the monoclonal antibody in connection with the pathogenesis of autoimmune diseases was discussed.     

Sexual pleasure in women with obsessive-compulsive disorder?

BACKGROUND: Although patients with OCD have reported sexual dissatisfaction frequently, controlled studies are sparse. This study compared subjective appreciation of sexuality and sexual functioning between OCD patients and healthy subjects and controlled for the influence of medication or OCD subtypes on sexual functioning and satisfaction. METHODS: Self-report questionnaires were sent to 350 female outpatients with OCD and 101 questionnaires were completed. RESULTS: OCD patients reported significantly more sexual disgust (t = 4.48, p < 0.001), less sexual desire (t = 5.52, p < 0.001), sexual arousal (t = 4.28, p < 0.001), and satisfying orgasms (t = 4.94, p < 0.001), than controls. Neither medication nor OCD phenotypes did affect outcome. LIMITATIONS: A self-report questionnaire and relatively low response-rate (29%) could have biased the results and the sample was limited to women so results might not be generalisable to men. CONCLUSIONS: Female patients with OCD report low sexual pleasure, high sexual disgust and diminished sexual functioning, which are not only attributed to medication or contamination obsessions. In the future, clinicians should explicitly ask for sexual function in the assessment of patients with OCD.     

Segment difficulty in two-stroke movements in patients with Parkinson’s disease

In the horizontal plane on a digitizer tablet, subjects made an elbow-extension, two-stroke movement away from the trunk to a first target and then on to a second target. If the two segments of the movement were executed in an integrative manner, the accuracy constraint on the first segment should have produced changes in kinematic features not only of that segment but also of the second segment. Two-stroke movements of ten Parkinson's disease (PD) patients and ten controls were studied to examine whether a high-accuracy constraint on the first segment influences the performance of the second, when the second target has either a high- or low-accuracy requirement. When the accuracy requirement of the second segment was low, both PD patients and controls showed that changing the first target size from large to small influenced the performance of not only the first segment but also the second segment. For the first segment, movement time, acceleration time, and deceleration time increased when moving to the small first target as compared to the large first target. The peak velocity and peak acceleration also decreased as the first target size decreased. For the second segment, similar patterns of kinematic changes in relation to the first segment were observed in all of these parameters. When the accuracy requirement of the second segment was high, the controls showed similar changes in the first and second segments in relation to the change of first target sizes. In contrast, the PD patients showed that the target size that defined the first movement mainly influenced the performance of that segment. Among kinematic parameters tested for the second segment, only acceleration time increased as the first target size decreased. Other parameters in general did not change, regardless of whether movement of the first segment was made to the small or large target. These results indicate that the two-stroke movements of PD patients showed little evidence that they were planned and organized in an integrative manner when there was a high-accuracy constraint imposed on the second segment. On the other hand, control subjects performed two-stroke movements in a manner that suggested the two segments were planned and organized together regardless of an accuracy constraint imposed.     

Guillain-Barré syndrome in child with prolong intubation

Guillain-Barré syndrome (GBS) is an acute demyelinating disorder of the peripheral nervous system that results from an aberrant immune response directed at peripheral nerves. A typical GBS patient presents with rapidly ascending symmetrical weakness, which may progress to respiratory failure in 30% of patients. There are no definite criteria exists in GBS in children regarding prolonged ventilation. Here we report a child of GBS requiring prolonged intubation and ventilation for 60 days who afterward had a complete recovery. We present this case to highlight the importance that even in children prolonged intubation and ventilation of GBS case prognosis can be good.     

Does activity in research correlate with visibility?

BACKGROUND: A previous survey has highlighted the fact that most individuals in chemical pathology identifiable from specialist society membership failed to publish material in Medline cited journals during a five year period. It could be considered that published research that is not cited in other work is not useful unless it has achieved visibility, as demonstrated by citation in another research publication. AIMS: To determine whether the frequency of research publication is associated with research visibility. METHODS: A random selection from the previous survey was investigated to determine whether the frequency of research publication is associated with research visibility. RESULTS: There was a logarithmic relation between the frequency of publication and visibility, with an increasing probability of citation as publication frequency increases. CONCLUSIONS: If academic activity is to survive then individuals must stay active in research; this requires a continuing commitment to a tradition of support for individuals at all stages of their careers engaging in research.     

Bisphenol A in combination with TNF-α selectively induces Th2 cell-promoting dendritic cells in vitro with an estrogen-like activity

Bisphenol A (BPA) is a monomer used in manufacturing a wide range of chemical products, including epoxy resins and polycarbonate. BPA, an important endocrine disrupting chemical that exerts estrogen-like activities, is detectable at nanomolar levels in human serum worldwide. The pregnancy associated doses of 17β-estradiol (E2) plus tumor-necrosis factor-α (TNF-α) induce distorted maturation of human dendritic cells (DCs) that result in an increased capacity to induce T helper (Th) 2 responses. The current study demonstrated that the presence of BPA during DC maturation influences the function of human DCs, thereby polarizing the subsequent Th response. In the presence of TNF-α, BPA treatment enhanced the expression of CC chemokine ligand 1 (CCL1) in DCs. In addition, DCs exposed to BPA/TNF-α produced higher levels of IL-10 relative to those of IL-12p70 on CD40 ligation, and preferentially induced Th2 deviation. BPA exerts the same effect with E2 at the same dose (0.01–0.1 µΜ) with regard to DC-mediated Th2 polarization. These findings imply that DCs exposed to BPA will provide one of the initial signals driving the development and perpetuation of Th2-dominated immune response in allergic reactions.     

Hypoxia inducible factor 1α in hepatocellular carcinoma with cirrhosis: Association with prognosis

Background

Hypoxia inducible factor 1α (HIF-1α) is a protein related with carcinogenesis and metastasis in many tumors. However, little is known about the prognostic value of HIF-1α in hepatocellular carcinoma (HCC) patients with cirrhosis.

Aberrant Fas ligand expression in lymphocytes in patients with Behçet's disease

BACKGROUND: Defects in immune responses have been reported in patients with Beh?et's disease (BD). To further characterize the immune dysfunction and its contribution to the pathogenesis, we have studied Fas ligand (FasL) expression in peripheral blood lymphocytes (PBL) and mononuclear cells in the skin lesions in patients with BD. METHODS: FasL expression in PBL was studied with RT-PCR and immunoblotting with rabbit anti-human FasL antibody. We studied the expression of FasL in cryostat sections of biopsy specimens of erythema nodosum lesions from 4 patients with BD and of a genital ulcer lesion in another patient using immunohistochemical staining. Apoptotic cell death was detected with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. RESULTS: We found that FasL mRNA and FasL protein expression was detected marginally in the unstimulated PBL, and was induced upon activation in normal individuals. PBL from patients with BD exhibited an enhanced expression of FasL mRNA and FasL protein without in vitro stimulation. Moreover, mitogen stimulation failed to augment FasL expression of their lymphocytes, suggesting a dysregulation of FasL expression of PBL in patients with BD. The skin biopsy specimens revealed that cells infiltrating into skin lesions expressed FasL and there were several TUNEL staining-positive cells in the lesions, suggesting that Fas/FasL-mediated apoptosis is involved in the development of the skin lesion and thus may be associated with the pathogenesis. CONCLUSIONS: We found an excessive expression of FasL in circulating as well as skin-infiltrating lymphocytes and the presence of apoptotic cells in the skin lesions, suggesting that lymphocytes expressing FasL aberrantly may play a role in the development and pathogenesis of BD.     

Are cytokines associated with neuropsychiatric syndromes in humans?

Traditional aetiological models in neuropsychiatry have placed little emphasis on the abnormal behavioural responses (decreased psychomotor activity, anorexia, weight loss, decreased social exploration and sexual behaviour, impaired cognitive function and increased somnolence) that are common to both psychiatric syndromes, notably depression, and the illness behaviour of sick animals. In recent years, the possible role of cytokines, as mediators of not only the immunological and metabolic responses to infection and inflammation but also a co-ordinated behavioural response, has been described. Further, a range of possible mechanisms for these effects has been postulated, notably involving corticotropin releasing factor (CRF) and prostaglandins of the E series (PgE) with the central nervous system (CNS). Here we outline a series of human clinical conditions where neuropsychiatric syndromes co-occur with a host response to infection or inflammation. These may be characterized by cytokine production (e.g. acute, recurrent and chronic viral illnesses, systemic autoimmune diseases and chronic fatigue syndrome). Other clinical situations characterized by exposure to or in vivo production of cytokines (e.g. treatment of chronic infections and malignancies, progression and/or recurrence of malignancies) are also discussed. We postulate that the stereotyped behavioural repertoire observed is mediated by cytokine-dependent mechanisms within the CNS. Systematic studies of the behavioural responses of such patient groups are suggested, noting specifically correlations between the time course and severity of immune and neuroendocrine and behavioural responses and dose-response effects.