Platelet serotonin transporter in schizophrenic patients with and without neuroleptic treatment

Among various hypotheses put forth to account for the etiology of schizophrenia, the abnormal function of serotonergic system has recently gained marked interest. Our previous study showed that drug-free schizophrenic patients had a significant increase in maximum numbers (B(max)) of platelet 5-HT(2A) receptors that declined to normal level after treatment with different neuroleptic drugs. To elucidate the role of the serotonin system in schizophrenia, the serotonin transporters on human platelets were examined in this study. Platelet serotonin transporters obtained from normal control subjects and schizophrenic patients were identified by using [(3)H]imipramine as the radioligand and fluoxetine to define the non-specific binding. The data showed that the mean B(max) of serotonin transporter sites for schizophrenic patients without neuroleptic therapy was significantly higher than in normal controls. The B(max) values for schizophrenic patients on phenothiazine, butyrophenone, thioxanthene and serotonin-dopamine antagonist (SDA) therapies were significantly lower than the B(max) values obtained from schizophrenic patients without neuroleptic therapy, and were comparable to those found in normal control subjects. The dissociation equilibrium constant (K(d)) values in all subject groups remained unchanged. The effect of various medication periods on platelet serotonin transporters was also studied. We found that, B(max) values of 1-4 weeks, 1-4 months, 4-12 months and >1 year of neuroleptic therapies were significantly decreased when compared with the unmedicated group. Significant reduction of brief psychiatric rating scale (BPRS) occurred in all types of neuroleptics and every period of drug treatments compared with the unmedicated group. The present results indicate that alteration of platelet serotonin transporters is associated with schizophrenia. Treatment with various types of neuroleptics suppresses the hypersensitivity of platelet serotonin transporters. The mechanisms of how neuroleptics achieve their therapeutic effects, whether they act via or modulate serotonin system in certain brain area, still need to be further evaluated.     

A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozoites

Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and invade hepatocytes as a first and obligatory step of the parasite life cycle in man. Hepatocyte invasion involves proteins secreted from parasite vesicles called micronemes, the most characterized being the thrombospondin-related adhesive protein (TRAP). Here we investigated the expression and function of another microneme protein recently identified in Plasmodium falciparum sporozoites, apical membrane antigen 1 (AMA-1). P. falciparum AMA-1 is expressed in sporozoites and is lost after invasion of hepatocytes, and anti-AMA-1 antibodies inhibit sporozoite invasion, suggesting that the protein is involved during invasion of hepatocytes. As observed with TRAP, AMA-1 is initially mostly sequestered within the sporozoite. Upon microneme exocytosis, AMA-1 and TRAP relocate to the sporozoite surface, where they are proteolytically cleaved, resulting in the shedding of soluble fragments. A subset of serine protease inhibitors blocks the processing and shedding of both AMA-1 and TRAP and inhibits sporozoite infectivity, suggesting that interfering with sporozoite proteolytic processing may constitute a valuable strategy to prevent hepatocyte infection.     

采用PCR-测序法对北京地区325例妇女宫颈脱落细胞样品中人乳头瘤病毒进行检测和基因分型

为了探讨PCR-测序法在宫颈脱落细胞样品中人乳头瘤病毒 (Human papillomavirus, HPV) 临床检测中的应用价值,采用HPV通用引物PGMY09/11针对HPV L1区基因序列进行PCR扩增,并通过DNA测序法对HPV进行基因分型。对于混合感染样品,利用HPV型别特异性引物PCR的方法进行基因分型。325例临床样品中,228例为HPV阳性,其中66例为混合感染。共发现27种不同的HPV型别,其中HPV 16比例最多,其次是HPV 58和52。高危型HPV检出率随病变程度加重显著性增加     

Roles of cyclic AMP in regulation of phototaxis in <Emphasis Type="Italic">Chlamydomonas reinhardtii</Emphasis>

Chlamydomonas reinhardtii swims toward or away from light (phototaxis) in a graded way depending on various conditions. Activation of rhodopsin provides signals to control the steering of this unicellular organism relative to a light source and to up-regulate rhodopsin biosynthesis. Intracellular cAMP and cGMP concentrations were measured in positive (1117, swims toward light) and negative (806, swims away from light) phototactic strains with and without light stimulation or 3-isobutyl-1-methylxanthine (IBMX). In the dark, the levels of cAMP and cGMP were significantly higher in the strain with positive phototaxis than in the strain with negative phototaxis. To test whether either cyclic nucleotide influenced the direction, their pre-stimulus levels were pharmacologically manipulated. Higher pre-stimulus levels of cAMP biased the cells to swim toward green light and lower levels biased the cells to swim away. In addition, green-light activation of rhodopsin or addition of IBMX causes a sustained increase in cAMP in both strains. As a consequence of this increase in cAMP, carotenogenesis is induced, as shown by recovery of phototaxis in a carotenoid mutant. Thus, two functions for cAMP were identified: high pre-stimulus level biases swimming toward a light source and sustained elevation following rhodopsin activation increases rhodopsin biosynthesis.     

Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus

Electrolyzed reduced water, which is capable of scavenging reactive oxygen species, is attracting recent attention because it has shown improved efficacy against several types of diseases including diabetes mellitus. Alloxan produces reactive oxygen species and causes type 1 diabetes mellitus in experimental animals by irreversible oxidative damage to insulin-producing β-cells. Here, we showed that electrolyzed reduced water prevented alloxan-induced DNA fragmentation and the production of cells in sub-G1 phase in HIT-T15 pancreatic β-cells. Blood glucose levels in alloxan-induced type 1 diabetes model mice were also significantly suppressed by feeding the mice with electrolyzed reduced water. These results suggest that electrolyzed reduced water can prevent apoptosis of pancreatic β-cells and the development of symptoms in type 1 diabetes model mice by alleviating the alloxan-derived generation of reactive oxygen species.     

Structure and antioxidant activity of an extracellular polysaccharide from coral-associated fungus, Aspergillus versicolor LCJ-5-4

An extracellular polysaccharide AVP was isolated from the fermented broth of coral-associated fungus Aspergillus versicolor LCJ-5-4. AVP was a mannoglucan with molecular weight of about 7 kDa, and the molar ratio of glucose and mannose was 1.7:1.0. On the basis of detailed one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic analyses, the backbone of AVP was characterized to be composed of (1 → 6)-linked α-d-glucopyranose and (1 → 2)-linked α-d-mannopyranose units. The mannopyranose residues in the backbone were substituted mainly at C-6 by the side chain of (1 → 2)-linked α-d-mannopyranose trisaccharides units. The antioxidant activity of AVP was evaluated with the scavenging abilities on 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals in vitro, and the results indicated that AVP had good antioxidant activity, especially scavenging ability on superoxide radicals. AVP was a novel extracellular polysaccharide with different structural characteristics from other extracellular polysaccharides and could be a potential source of antioxidant.     

HLA-DRB1 and HLA-DQB1 Are Associated with Adult-Onset Immunodeficiency with Acquired Anti-Interferon-Gamma Autoantibodies

Recently a newly identified clinical syndrome of disseminated non-tuberculous mycobacterial diseases (with or without other opportunistic infections in adult patients who were previously healthy, has been recognized in association with an acquired autoantibody to interferon-gamma. This syndrome is emerging as an important cause of morbidity and mortality, especially among people of Asian descent. Trigger for the production of this autoantibody remains unknown, but genetic factors are strongly suspected to be involved. We compared HLA genotyping between 32 patients with this clinical syndrome, and 38 controls. We found that this clinical syndrome was associated with very limited allele polymorphism, with HLA-DRB1 and DQB1 alleles, especially HLA-DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02. Odds ratio of DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02 were 7.03 (95% CI, 2.18–22.69, P<0.0001, 9.06 (95% CI, 2.79–29.46, P<0.0001), 6.68 (95% CI, 2.29–19.52, P = 0.0004), and 6.64 (95% CI, 2.30–19.20, P = 0.0004), respectively. Further investigation is warranted to provide better understanding on pathogenesis of this association.     

Arterial spin labeling blood flow magnetic resonance imaging for evaluation of renal injury

A multitude of evidence suggests that iodinated contrast material causes nephrotoxicity; however, there have been no previous studies that use arterial spin labeling (ASL) blood flow functional magnetic resonance imaging (fMRI) to investigate the alterations in effective renal plasma flow between normointensive and hypertensive rats following injection of contrast media. We hypothesized that FAIR-SSFSE arterial spin labeling MRI may enable noninvasive and quantitative assessment of regional renal blood flow abnormalities and correlate with disease severity as assessed by histological methods. Renal blood flow (RBF) values of the cortex and medulla of rat kidneys were obtained from ASL images postprocessed at ADW4.3 workstation 0.3, 24, 48, and 72 h before and after injection of iodinated contrast media (6 ml/kg). The H&E method for morphometric measurements was used to confirm the MRI findings. The RBF values of the outer medulla were lower than those of the cortex and the inner medulla as reported previously. Iodinated contrast media treatment resulted in decreases in RBF in the outer medulla and cortex in spontaneously hypertensive rats (SHR), but only in the outer medulla in normotensive rats. The iodinated contrast agent significantly decreased the RBF value in the outer medulla and the cortex in SHR compared with normotensive rats after injection of the iodinated contrast media. Histological observations of kidney morphology were also consistent with ASL perfusion changes. These results demonstrate that the RBF value can reflect changes of renal perfusion in the cortex and medulla. ASL-MRI is a feasible and accurate method for evaluating nephrotoxic drugs-induced kidney damage.