LncRNA DSCAM-AS1 promoted cell proliferation and invasion in osteosarcoma by sponging miR-101.

OBJECTIVE: Long noncoding RNAs (lncRNAs) play critical roles in osteosarcoma (OS) progression. LncRNA DSCAM-AS1 has been reported to function as a tumor promoter in various cancers. However, the potential mechanism of DSCAM-AS1 in OS remains rarely know. PATIENTS AND METHODS: The expression levels of DSCAM-AS1 and miR-101 were detected by RT-qPCR. The correlation between DSCAM-AS1 and miR-101 expression was analyzed by Pearson's correlation. Kaplan-Meier analysis was used to assess the overall survival rate. Cell viability and invasion were assessed by MTT assay and transwell assays, respectively. A Luciferase reporter assay was used to identify the relationship between DSCAM-AS1 and miR-101. RESULTS: In the present study, it was demonstrated that DSCAM-AS1 expression was significantly upregulated in OS tissues and cells and high expression of DSCAM-AS1 predicted poor prognosis in OS patients. In addition, the silencing of DSCAM-AS1 suppressed the viability and invasion of OS cells, while DSCAM-AS1 overexpression promoted cell viability and invasion. Furthermore, we found that DSCAM-AS1 inhibited miR-101 expression by direct interaction and DSCAM-AS1 promoted OS progression by sponging miR-101. In addition, miR-101 expression was negatively correlated with DSCAM-AS1 expression. Patients with low miR-101 expression had a shorter overall survival time compared with those with high miR-101 expression. CONCLUSIONS: The present study demonstrated that DSCAM-AS1 accelerated OS cell progression by sponging miR-101, which might provide a new sight in the treatment of OS.

[Prevalence of tonsilloliths and CT diagnosis].

Objective: To investigate the prevalence, gender and age distribution characteristics of tonsilloliths and its CT diagnosis, in order to improve the knowledge of clinicians. Methods: The images of 2 710 patients who underwent head and neck CT scans from November 2015 to November 2016 were retrospectively reviewed, the prevalence, gender and age distribution of tonsilloliths and CT manifestation were analyzed. SPSS 18.0 was used for statistical analysis. Results: Tonsilloliths were found in 383 (14.1%) of the 2 710 patients, including 217 men and 166 women. The prevalence was 15.1% in men and 13.1% in women, and no gender difference was seen. The age of patients with tonsilloliths ranged from 6-88 years, and the mean age was (51.1±16.8) years. The prevalence of tonsilloliths in patients 40 years and younger was significantly lower than in those who were over 40 years (χ(2)=15.201, P<0.001), and the prevalence of tonsilloliths was positively correlated with age(r=0.812, P=0.008). One hundred and twenty eight cases of tonsilloliths were located on the right side, and 157 were located on tleft side. Tonsilloliths were detected bilaterally in 98 patients. There was no significant difference between left and right sides(χ(2)=1.919, P=0.166). Most of tonsilloliths showed a single small tonsillolith, 60.6% of tonsilloliths showed only one tonsillolith, whereas 39.4% showed two or more. The size of tonsilloliths ranged from 1.0 to 10.0 mm, the mean maximum diameter was (2.3±1.2) mm, and 86.7% of tonsilloliths with a maximum diameter of no more than 3.0 mm. Tonsilloliths showed dot, round or oval hyperdense in tonsillar crypt or parenchyma. CT attenuation of majority tonsilloliths was over 120 Hu. Conclusion: Tonsilloliths are more common than previously suggested, its CT diagnosis is not difficult, and the knowledge of clinician and radiologist needs to be improved.

Testes-specific protease 50 promotes cell proliferation via inhibiting activin signaling.

Testes-specific protease 50 (TSP50), a novelly identified oncogene, has the capacity to induce cell proliferation, cell invasion and tumor growth. Further studies indicated that CAGA-luc (an activin-responsive reporter construct) reporter activity could be significantly suppressed by TSP50 overexpression, implying that the activin signaling may participate in TSP50-mediated cell proliferation. Here, we reported that TSP50 had an inhibitory effect on activin signaling. Mechanistic studies revealed that TSP50 could interact with ActRIIA, inhibit activin typeIreceptor (ActRIB) phosphorylation, repress Smad2/3 nuclear accumulation and finally promote cell proliferation by reducing the expression of activin signal target gene p27. Additionally, we found that ActRIB activation could reverse TSP50-mediated cell proliferation and tumor growth. Furthermore, analysis of human breast cancer specimens by immunohistochemistry indicated that TSP50 expression was negatively related to p-Smad2/3 and p27 protein levels. Most importantly, breast cancer diagnosis-related indicators such as tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) levels, were correlated well with TSP50/p-Samd2/3 and TSP50/p27 expression status. Thus, our studies revealed a novel regulatory mechanism underlying TSP50-induced cell proliferation and provided a new favorable intervention target for the treatment of breast cancer.

Combination of nifedipine and subtherapeutic dose of cyclosporin additively suppresses mononuclear cells activation of patients with rheumatoid arthritis and normal individuals via Ca(2+) -calcineurin-nuclear factor of activated T cells pathway.

Abnormal Ca(2+) -mediated signalling contributes to the pathogenesis of rheumatoid arthritis (RA). However, the potential implication of calcium channel blocker in RA remained unknown. We hypothesized that nifedipine, an L-type calcium channel blocker, combined with a calcineurin inhibitor, could suppress T cell activation via targeting different level of the Ca(2+) signalling pathway. The percentage of activated T cells and the apoptotic rate of mononuclear cells (MNCs) was measured by flow cytometry. The MNC viability, cytokine production, cytosolic Ca(2+) level and activity of the nuclear factor of activated T cells (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT-regulated gene expression, including interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF), was measured by real-time polymerase chain reaction (PCR). We found that the percentage of activated T cells in anti-CD3 + anti-CD28-activated MNC was higher in RA patients. High doses of nifedipine (50 µM) increased MNCs apoptosis, inhibited T cell activation and decreased T helper type 2 (Th1) (IFN-γ)/Th2 (IL-10) cytokine production in both groups. The Ca(2+) influx was lower in anti-CD3 + anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed by nifedipine. When combined with a subtherapeutic dose (50 ng/ml) of cyclosporin, 1 µM nifedipine suppressed the percentage of activated T cells in both groups. Moreover, this combination suppressed more IFN-γ secretion and NFAT-regulated gene (GM-CSF and IFN-γ) expression in RA-MNCs than normal MNCs via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca(2+) channel blockers and subtherapeutic doses of cyclosporin act additively to suppress the Ca(2+) -calcineurin-NFAT signalling pathway, leading to inhibition of T cell activity. We propose that this combination may become a potential treatment of RA.

Genetic susceptibility to occupational exposures.

Because of their high prevalence in the general population, genetic variants that determine susceptibility to environmental exposures may contribute greatly to the development of occupational diseases in the setting of specific exposures occurring in the workplace. Studies investigating genetic susceptibilities in the workplace may: (1) provide mechanistic insight into the aetiology of disease, in particular the determination of environmentally responsive genes; (2) identify susceptible subpopulations with respect to exposure; and (3) provide valuable input in setting occupational exposure limits by taking genetic susceptibility into account. Polymorphisms in the NAT2 and the HLA-DPB1(G)(lu69) genes provide classic examples of how genetic susceptibility markers have a clear role in identifying disease risk in bladder cancer and chronic beryllium disease, respectively. For diseases with more complex and multifactorial aetiology such as occupational asthma and chronic airways disease, susceptibility studies for selected genetic polymorphisms provide additional insight into the biological mechanisms of disease. Even when polymorphisms for genetic susceptibility have a clear role in identifying disease risk, the value of wide scale genetic screening in occupational settings remains limited due to primarily ethical and social concerns. Thus, large scale genetic screening in the workplace is not currently recommended.

MR T1-weighted inversion recovery imaging in detecting brain metastases: could it replace T1-weighted spin-echo imaging?

BACKGROUND AND PURPOSE: T1-weighted inversion recovery (T1IR) imaging demonstrates higher brain tissue contrast and is more sensitive to contrast enhancement than T1-weighted spin-echo (T1SE) imaging. However, the effectiveness of the 2 imaging sequences in detecting brain metastases has not been studied. The objective of this report was to determine which sequence should be used for detecting brain metastases by comparing the effectiveness of T1IR imaging with that of T1SE imaging. MATERIALS AND METHODS: Thirty-one patients with brain metastases underwent T1SE and T1IR with and without intravenous gadopentetate dimeglumine. T1SE and T1IR images were compared for the number of metastases, degree of contrast enhancement, volume and contrast-to-enhancement ratio (CER) of tumors, and contrast ratio (CR) of tumor to white matter (WM), tumor to gray matter (GM), and tumor to CSF. RESULTS: There were 352 metastases in 31 patients, among which 2 patients with 5 metastases were demonstrated only on postenhanced T1SE images. Pre-enhanced and postenhanced T1SE images detected 162 and 350 lesions, respectively, whereas pre-enhanced and postenhanced T1IR images only discovered 94 and 233 lesions. The degree of tumor contrast enhancement was higher on T1IR images than on T1SE images, whereas no difference in the CER of tumors was found between the 2 sequences. Before enhancement, all of the CRs on T1IR images were higher than on T1SE images. After contrast enhancement, CRs of tumor to WM and tumor to GM were higher on T1SE images than on T1IR images. On the contrary, the CR of tumor to CSF was higher on T1IR images than on T1SE images. Tumor volumes were 5.6 +/- 7.0 cm(3) on postenhanced T1SE images and 5.5 +/- 7.0 cm(3) on postenhanced T1IR images, and no significant difference was found between the 2 groups. CONCLUSION: T1SE, but not T1IR, should be used as T1-weighted imaging in detecting brain metastases, because T1SE imaging has a greater sensitivity than T1IR imaging both before and after contrast material administration.

Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-kappaBp65-specific siRNA.

OBJECTIVE: This study was to use adenoviral vector-mediated nuclear factor-kappaBp65 (NF-kappaBp65)-specific siRNA (Ad-siRNA(NF-kappaBp65)) to suppress the progression of early osteoarthritis (OA) in rat model, and therefore to explore a new gene therapy for OA. METHODS: Reverse transcription polymerase chain reaction was performed to confirm the silencing effect of Ad-siRNA(NF-kappaBp65) in cultured rat chondrocytes. Transection of the medial collateral ligament plus partial medial meniscectomy was operated in the knee of rats to establish OA model. Histological analysis was made to assess the morphological change of cartilage and synovium, and enzyme-linked immunosorbent assay was made to measure the expression of cytokines, such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), in synovial fluid. The silencing effect of Ad-siRNA(NF-kappaBp65) on NF-kappaBp65 in cartilage and synovium of knee was measured with Western blot and the activation of NF-kappaB was measured with electrophoretic mobility shift assays. RESULTS: Ad-siRNA(NF-kappaBp65) can inhibit the activation of NF-kappaB and the expression of NF-kappaBp65 in cartilage and synovium of the knee, restrain the induction of IL-1beta and TNF-alpha in synovial fluid, alleviate the inflammation of synovium and reduce the degradation of cartilage in early phase of experimental OA. CONCLUSIONS: Ad-siRNA(NF-kappaBp65) can suppress the progression of the early experimental OA which suggests that Ad-siRNA(NF-kappaBp65) has potential to be a useful preventive and therapeutic agent for OA.

Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophils.

Anti-neutrophil cytoplasmic antibodies (ANCA) not only are triggered by target protein myeloperoxidase (MPO) and proteinase 3 (PR3) of polymorphonuclear neutrophil (PMN) but also react with primed PMN to exert the inflammatory process in vasculitis syndrome. To clarify the crucial role of PMN in ANCA-associated vasculitis and the related mechanism, PMN was cultured with monoclonal antibody MPO-ANCA and PR3-ANCA to determine the function of phagocytosis, Interleukin- 8 (IL-8) production, glucose uptake, and TNF-related apoptosis induced ligand (TRAIL) production. The spontaneous membrane expression of MPO and PR3 on PMN could be significantly increased by lipopolysaccharide (LPS) and TNF-alpha, but not by IL-8 or GRO-alpha. The PMN-stimulating activity of ANCA was demonstrated by enhancing phagocytosis, IL-8 production, and glucose uptake that was more prominent by MPO-ANCA. The PMN stimulation by ANCA was not through protein kinase, H2O2, or superoxide anion radicals as their inhibitors exerted no effect on ANCA-mediated activation. On the other hand, ANCA also accelerated PMN apoptosis and increased TRAIL production. These results demonstrate that activation-induced cell death (AICD) mechanism could be initiated in PMN with existence of ANCA. In conclusion, MPO-ANCA is more potent in stimulating PMN than PR3-ANCA. ANCA-activated PMN is not only responsible for the amplified inflammatory process in blood vessel but also initiates immune circuit via triggered macrophage/monocyte by apoptotic PMN through the mechanism of AICD elicited by ANCA.

Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease type C.

In patients with Niemann-Pick disease type C (NPC), an autosomal recessive lipid storage disorder, neurodegeneration can occur in early life. Vertical ophthalmoplegia and extrapyramidal signs may be seen. Cholestatic jaundice and hepatosplenomegaly occur frequently in patients with early onset disease, with bone marrow biopsies showing diffuse infiltration of foamy histiocytes. Cholesterol esterification in skin fibroblasts is reduced, resulting in intracellular accumulation of cholesterol. NPC1 mutations are responsible for the disease in approximately 95% of patients. NPC1 encodes a 1278 amino acid protein which contains 13 transmembrane domains. Over 130 mutations have been identified in NPC1, with over a third present within an NPC1 specific cysteine-rich domain positioned in a large extracellular loop. It has been proposed that the defect in cholesterol homoeostasis is the cause of neuronal apoptosis, but the precise role of the NPC1 protein and the functional implications of its mutations remain unknown. Although NPC is routinely diagnosed by biochemical analysis, identification of molecular defects helps confirm the diagnosis and enables family studies, and rapid, accurate prenatal diagnosis. This report describe the analysis of the NPC1 gene in five Taiwanese/Chinese patients with NPC. Six novel NPC1 mutations (N968S, G1015V, G1034R, V1212L, S738Stop, and I635fs) were identified of which three are missense mutations located in the cysteine-rich domain. These are the first NPC1 mutations reported from Chinese patients with NPC.

Anti-CD45 isoform antibodies enhance phagocytosis and gene expression of IL-8 and TNF-alpha in human neutrophils by differential suppression on protein tyrosine phosphorylation and p56lck tyrosine kinase.

To determine the biological functions of membrane expressed CD45 isoforms on polymorphonuclear neutrophils (PMN), the monoclonal IgG F(ab')2 antibody against CD45, CD45RA or CD45RO was used as surrogate ligand for binding with these molecules on PMN. We found 99.5 +/- 3.2%, 42.3 +/- 5.8% and 96.7 +/- 2.6% PMN expressed CD45, CD45RA and CD45RO molecules on the cell surface, respectively. The interaction of CD45, CD45RA or CD45RO with its specific antibody on PMN enhanced phagocytosis markedly (34-83% increase), mainly via increased expression of complement receptor type 3 (CR3, CD11b) on the cells. The production of IL-8 by PMN was also increased significantly after binding with antibodies (anti-CD45 > anti-CD45RO > anti-CD45RA). Anti-CD45RA and anti-CD45RO, but not anti-CD45, enhanced TNF-alpha mRNA expression and decreased protein tyrosine phosphorylation of PMN. However, only anti-CD45RO suppressed Src family protein tyrosine kinase p56lck expression in the cells. These results suggest that the cross-linking of CD45 isoforms by their specific antibodies stimulated different PMN activities by differential suppression on protein tyrosine phosphorylation and Src family tyrosine kinase p56lck.

Chinese nasopharyngeal carcinoma patients treated with radiotherapy: association between satisfaction with information provided and quality of life.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China. Prominent acute side effects of radiotherapy create problems in daily living and working that can generate considerable financial difficulties. A better adjustment to a diagnosis of NPC appears to be associated with an improved rate of recovery, a better quality of life (QoL), a quicker return to work, and normal functioning. Patient satisfaction with physician consultation and the way information is provided in particular may have significant bearing on QoL. The current study reports on short-term QoL after radiotherapy in NPC patients as a function of satisfaction with the information provided. METHODS: Newly referred Hong Kong Chinese NPC patients (n = 211) completed interview measures at baseline before the initiation of radiotherapy, at 4 months after baseline (immediate posttreatment consultation) (FU 1), and again at 8 months (short-term postradiation period) after baseline (FU 2). Satisfaction with the information provided was measured by five items selected from the cognitive subscale of the Medical Interview Satisfaction Scale (MISS). QoL was measured by the Chinese version of the Functional Assessment of Cancer Therapy-General Scale (FACT-G (Ch)). RESULTS: After adjustment for overall patient satisfaction (the PSQ-9), optimism, worry about family, anger, eating ability, subjective health, family income, and occupation at FU 1, treatment between baseline and FU 1, and disease recurrence after baseline, the 5-item MISS at FU 1 (beta = 0.21, P < 0.01) was found to significantly predict patient QoL at FU 2. Adjustment for baseline QoL and disease stage did not appear to alter this relation (beta = 0.20, P < 0.01). CONCLUSIONS: To the authors' knowledge, there is very little research concerning NPC. The results of the current study reinforced the need to improve physicians' information provision during consultations with Chinese NPC patients shortly after the end of treatment.

Embryonic apoptosis-inducing proteins exhibited anticancer activity in vitro and in vivo.

A 54 Kd apoptosis-inducing protein with novel amino acid sequence has been purified from the conditioned medium of the embryonic cell line, C3H 10T1/2 cells. An apoptosis-inducing protein identified to be fetal fetuin and a 60 Kd apoptosis-inducing protein have also been found in fetal serum and fresh embryo extract, respectively. Interestingly, a common characteristic of these embryonic apoptosis-inducing proteins is that they selectively induced apoptosis in cancer without affecting normal cells. For example, the 54 Kd protein selectively induced apoptosis in 10 out of 12 cancer cell lines without affecting 12 normal cell lines we tested. Fetal fetuin, on the other hand, selectively induced apoptosis in 5 cancer cell lines without affecting the 3 normal cell lines we tested. In vivo, tumor animal model study showed that fetal fetuin enhanced survival in leukemia-bearing mice and strongly inhibited the formation of prostate cancer in a PC-3 prostate cancer model in mice. A working hypothesis has been proposed to aid in the study of the mechanism by which the embryonic apoptosis-inducing proteins selectively induced apoptosis in cancer without affecting normal cells. This hypothesis states that due to the retro-differentiational characteristic of malignancy, cancer cells may re-express the signal transduction machinery for development-related apoptosis, which is otherwise to be normally expressed by embryonic, but not by adult cells. The embryonic apoptosis-inducing proteins may therefore induced apoptosis in cancer but not in normal cells and may be developed as an anticancer agent. This new concept may constitute a new approach for cancer therapy, which we tentatively designated as "Retro-differentiational Apoptosis Cancer Therapy", (R-ACT).

Fetal fetuin selectively induces apoptosis in cancer cell lines and shows anti-cancer activity in tumor animal models.

An apoptosis-inducing protein with molecular weight of 60 kDa has been purified from fetal bovine serum. The N-terminal amino acid sequence of this protein (e.g. I-P-L-D-P-V-A-G-Y-K) reveals that it is bovine fetuin, a fetal protein functioning to control embryogenesis. The apoptosis-inducing activity of fetuin is totally dependent on zinc. Depletion of zinc ion from fetuin or substitution of zinc ion by barium ion completely abolished the apoptosis-inducing activity of fetuin. Interestingly, while the fetuin isolated from fetal serum selectively induces apoptosis in cancer without affecting normal cells, the fetuin isolated from mature serum is completely inactive. This suggests that the biological activity of fetuin is under developmental regulation. In vivo, tumor animal model studies showed that fetuin enhanced survival by up to 141% in P388 leukemia animal model in mice. Fetuin was also found to inhibit prostate cancer formation in a PC-3 prostate cancer model in mice.

Anti-dsDNA antibody up-regulates interleukin 6, but not cyclo-oxygenase, gene expression in glomerular mesangial cells: a marker of immune-mediated renal damage?

OBJECTIVE AND DESIGN: To determine whether anti-double stranded DNA antibody (anti-dsDNA) can affect the synthesis of eicosanoids and cytokines in rat glomerular mesangial cells (RMC). MATERIALS OR SUBJECTS: Glomerular mesangial cells were isolated and subcultured from Sprague-Dawley rats. Monoclonal anti-dsDNA (12B3 clone) was derived from autoimmune MRL-lpr/lpr mouse by hybridoma technology. METHODS: The mRNA expression of cyclo-oxygenase type 1 (COX-1), type 2 (COX-2), Th1 (IL-2 and IFN-gamma)/Th2 (IL-4 and IL-10) and proinflammatory (IL-6 and TNF-alpha) and anti-inflammatory (TGF-beta) cytokines of RMC +/- anti-dsDNA was detected by RT-PCR. The PGE2 production by RMC +/- anti-dsDNA was measured by ELISA. The statistical significance was assessed by non-parametric Wilcoxon signed rank test. RESULTS: We found RMC spontaneously expressed COX-1, but not COX-2. The incubation of RMC with anti-dsDNA (50 ng/ml) did not affect COX expression and PGE2 production by RMC. RMC also spontaneously expressed IL-6, TNF-alpha and TGF-beta mRNA. However, only IL-6 was up-regulated by anti-dsDNA. CONCLUSIONS: Increased IL-6 expression in RMC may become a marker of anti-dsDNA-mediated immune damage of mesangial cells.

Targeting Src homology 2 domain-containing tyrosine phosphatase (SHP-1) into lipid rafts inhibits CD3-induced T cell activation.

To study the mechanism by which protein tyrosine phosphatases (PTPs) regulate CD3-induced tyrosine phosphorylation, we investigated the distribution of PTPs in subdomains of plasma membrane. We report here that the bulk PTP activity associated with T cell membrane is present outside the lipid rafts, as determined by sucrose density gradient sedimentation. In Jurkat T cells, approximately 5--10% of Src homology 2 domain-containing tyrosine phosphatase (SHP-1) is constitutively associated with plasma membrane, and nearly 50% of SHP-2 is translocated to plasma membrane after vanadate treatment. Similar to transmembrane PTP, CD45, the membrane-associated populations of SHP-1 and SHP-2 are essentially excluded from lipid rafts, where other signaling molecules such as Lck, linker for activation of T cells, and CD3 zeta are enriched. We further demonstrated that CD3-induced tyrosine phosphorylation of these substrates is largely restricted to lipid rafts, unless PTPs are inhibited. It suggests that a restricted partition of PTPs among membrane subdomains may regulate protein tyrosine phosphorylation in T cell membrane. To test this hypothesis, we targeted SHP-1 into lipid rafts by using the N-terminal region of Lck (residues 1--14). The results indicate that the expression of Lck/SHP-1 chimera inside lipid rafts profoundly inhibits CD3-induced tyrosine phosphorylation of CD3 zeta/epsilon, IL-2 generation, and nuclear mobilization of NF-AT. Collectively, these results suggest that the exclusion of PTPs from lipid rafts may be a mechanism that potentiates TCR/CD3 activation.

F wave monitoring during surgery for adult tethered cord syndrome--a case report.

We would like to report our first attempt in intraoperative study of F wave response electromyography (EMG) to monitor the spinal motor function during a spinal surgery for excision of a giant lumbosacral lipoma.

Anesthesia with deep hypothermic circulatory arrest for giant basilar aneurysm surgery.

The application of deep hypothermic circulatory arrest (DHCA) as an adjutant technique in anesthetic management for surgery of giant and complex cerebral aneurysm has been clinically recognized with piling up experience in many institutes. DHCA provides the advantages such as a bloodless surgical field and protection of the brain, all of which make a precise clipping of the aneurysm possible and thus it lowers the mortality rate which could be extremely high without it. Nevertheless, in application, the disadvantages of this technique includes comparatively inefficient and uneven cooling or rewarming, severe physiological change, cardiac distension and arrhythmia during cardiopulmonary bypass (CPB), hemorrhage from systemic heparinization and brain damage due to inadequate protection, none of which has ever been stressed. Since many giant aneurysms are found inoperable during exploration with application of DHCA, it would change the fate of the patients, and the clinical value of DHCA in such an instance becomes contradictive and disputable. We would like to present our experience in a case who, because of a giant basilar aneurysm, underwent surgical correction under DHCA retrograde cerebral perfusion (RCP) with cerebral function monitoring including electroencephalography (EEG), brainstem auditory evoked potentials (BAEP), thermal diffusion cerebral blood flowmetry, study of the change of extracellular concentration of excitatory amino acid, glutamate and aspartate, and off-line neurochemical analysis with cerebral microdialysis technique.

The in vitro immunomodulatory effects of sulfasalazine on human polymorphonuclear leukocytes, mononuclear cells, and cultured glomerular mesangial cells.

Sulfasalazine (SSA) was investigated for its effects on phagocytic activity of normal human polymorphonuclear neutrophils (PMN), proliferation of mononuclear cells (MNC) and cultured glomerular mesangial cells. At concentrations from 25 to 100 microM, it inhibited phagocytic activity of PMN and the 3H-thymidine incorporation of phytohemagglutinin (PHA)-stimulated human MNC in a dose-dependent manner. At comparable concentrations, sulfapyridine and 5-aminosalicylic acid, two of its major metabolites, did not show similar effects. SSA exhibited an inhibitory effect on both mouse and rat mesangial cells but at rather higher concentrations (0.5 mM). Excretion of interleukin (IL)-8 by lipopolysaccharide (LPS)-stimulated PMN was also markedly deterred in a dose-dependent manner but excretion of IL-8 by LPS-stimulated MNC was not interfered by SSA. Production of tumor necrosis factor (TNF)-alpha and IL-1beta by mouse mesangial cells was not blocked by SSA but production of IL-4 by these cells was inhibited by it (>0.1 mM). Inhibition of MNC was not due directly to cytotoxic effect of SSA on these cells as shown by fluorescein diacetate stain. Collectively, SSA inhibits phagocytosis and IL-8 excretion by PMN as well as mitogen-stimulated MNC reaction. On the other hand, at high concentrations, it inhibits glomerular mesangial cells and their IL-4 excretion but not TNF-alpha and IL-1beta excretion. These results can account for minimal nephrotoxic characteristic of SSA and suggest that it may be helpful in the treatment of immune-mediated glomerulonephritis.

Increased excretions of beta2-microglobulin, IL-6, and IL-8 and decreased excretion of Tamm-Horsfall glycoprotein in urine of patients with active lupus nephritis.

Tubulointerstitial nephritis is a less frequently recognized but important complication of systemic lupus erythematosus. We have investigated the cytokine beta2-microglobulin (beta2M) and Tamm-Horsfall glycoprotein (THG) excretions in the urine of systemic lupus erythematosus patients to identify indices for evaluation of tubulointerstitial inflammation in lupus nephritis (LN). Daily urine was collected from 15 patients with active LN, from 12 patients with inactive LN, and from 17 normal subjects. The amounts of soluble interleukin (IL) 2 receptor, IL-6, IL-8, beta2M, and THG in urine were measured. Beta2M and THG were regarded as indicators of proximal and distal renal tubule function, respectively. The urinary excretions of IL-6 and IL-8 were significantly higher in patients with active LN than in those with inactive LN and in normal individuals. The excretion of soluble IL-2 receptor in all three groups of subjects was not significantly different. On the other hand, the excretion of beta2M in patients with LN was significantly higher than that in normal individuals. The excretion of beta2M in patients with active or inactive LN was not significantly different. The THG excretion was lower in patients with active LN and tubulointerstitial inflammation as compared with patients with inactive LN or normal individuals. Six patients underwent pulse cyclophosphamide therapy during the course of experiments. Five of them showed a decrease in IL-8 and IL-6 excretions in urine after the treatment. The excretions of beta2M and THG in urine, in addition to IL-6 and IL-8, can reflect the renal inflammatory activity in patients with lupus tubulointerstitial nephritis as well as in those having lupus glomerulonephritis.