Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

Genetic immunization with GPI-anchored anthrax protective antigen raises combined CD1d- and MHC II-restricted antibody responses by natural killer T cell-mediated help

Studies have demonstrated that lipid rafts ultimately regulate the endocytosis of anthrax toxin via clathrin dependent pathway. Interestingly, GPI-anchored protein rich rafts have also been shown to be transported down to the endocytic pathway to reducing late endosomes. Taking advantage of this parallelism, we tried translating the anthrax toxin natural intoxication mechanism by administering a DNA chimera that encoded protective antigen attached to a mammalian GPI-anchor sequence at its C-terminus (pGPI-PA63). We also designed a chimera that had an additional N-terminal TPA leader sequence (pTPA.GPI-PA63) with an aim to target GPI-PA63 to ER where new CD1 molecules are synthesized. Analysis of antibody titers demonstrated successful priming and potential IgG titers after the first boost. In vitro cell proliferation studies in the presence of GPI-attached PA63 peptides revealed that there was a clonal expansion of CD4⁺ NK1.1⁺ helper T cell population which rapidly produced IL-4 in response to T cell receptor ligation. These cells provided direct B cell help that aided IgG formation. Effector responses generated by NKT cells were found to be MHC II-independent and CD1d-restricted. In addition, the group pTPA.GPI-PA63 also displayed low magnitude MHC-II restricted (CD1d-independent) NKT cell and CD4⁺ T cell helper responses in response to non-GPI attached PA63 peptides which overall resulted in the heightened responses seen for this group. Importantly, DNA vaccination mediated the generation of high avidity neutralizing antibodies that mediated protection against lethal toxin challenge.     

CD14+单核细胞人类白细胞抗原DR表达率与脓毒症关系的研究

目的了解烧伤延迟复苏时CDl4^＋单核细胞人类白细胞抗原DR（HLA—DR）表达率的变化，分析其与脓毒症的关系。方法选择烧伤面积大于30％TBSA的25例烧伤延迟复苏患者，于伤后1、3、7、14、28d取外周血，其中7例患者住院期间并发脓毒症，于脓毒症发生后连续2d亦取其外周血。另取20例健康体检者外周血作为对照。流式细胞仪检测CD14^＋单核细胞HLA．DR表达率，酶联免疫吸附测定法检测血浆中肿瘤坏死因子α（TNF—α）、白细胞介素10（IL-10）的浓度。结果非脓毒症患者伤后1、3、7、14、28dCD14^＋单核细胞HLA—DR表达率分别为（15±6）％、（74±5）％、（264±17）％、（284-16）％、（474-16）％，明显低于健康体检者[（924±10）％，P〈0．01]；脓毒症患者发生脓毒症后1、2d，该指标亦明显低于健康体检者及非脓毒症患者伤后1、7、14、28d（P〈0．01）。脓毒症患者TNF—d检出率及TNF—α、IL-10浓度，均高于非脓毒症患者和健康体检者（P〈0．05或P〈0．01）。伤后1、7、28d，外周血CD14^＋单核细胞HLA—DR表达率与IL—10浓度呈显著负相关（r分别为-0．9963、-0．7459、-0．8474，P〈0．01）。结论烧伤延迟复苏患者免疫功能低下，促炎性介质释放量增加，并发脓毒症时则更为严重。外周血CD14^＋单核细胞HLA—DR表达率可作为动态检测患者免疫功能状态的有效指标。     

Permanent prostate brachytherapy for Japanese men: Results from initial 100 patients with prostate cancer

OBJECTIVE: To evaluate the initial results of brachytherapy for prostate cancer with permanent iodine-125 implant in Japan. METHODS: The results obtained with brachytherapy in the initial 100 Japanese patients treated at Nagano Municipal Hospital were reviewed. Patients with a prostate-specific antigen (PSA) level of less than 10 ng/mL and a Gleason's scores of 5, 6, 3 + 4 were classified as having a low risk of recurrence. Patients with a PSA level of 10-20 ng/mL and/or a Gleason's score of 4 + 3 were classified as having an intermediate risk for recurrence. Seventy-eight of the low-risk patients and 19 of the intermediate-risk patients were treated by seed implants alone, or seed implants combined with preceding external radiation, respectively. A total of 53 patients received neoadjuvant hormone therapy. The efficacy and morbidity of brachytherapy were investigated using the serum PSA, International Prostate Symptom Score, quality of life score and uroflowmetry data. RESULTS: The average V100 and D90 obtained by post-implant dosimetry was 94.3 and 113.7%, respectively. Serum PSA decreased gradually after treatment, although it had still not reached a nadir after 1 year. There was little difference of the PSA level between the patients with and without neoadjuvant hormone therapy even at 1 year after seed implantation. There were no PSA biochemical failure or clinical recurrence during the follow-up period. Voiding symptoms worsened until 3 months after treatment, and then gradually improved. Acute urinary retention occurred transiently in one patient (1%). Rectal bleeding and severe diarrhea did not occur. CONCLUSION: Brachytherapy is a feasible and effective option for the treatment of prostate cancer in Japanese men. Brachytherapy may have a different effect in Japanese patients with respect to voiding symptoms. Urinary retention was rare, but voiding symptoms were persistent in Japanese patients. Neoadjuvant hormone therapy deserves investigation to determine whether it can achieve better results, especially in patients with an intermediate risk.     

乳腺癌患者癌胚抗原检测的临床意义

目的探讨癌胚抗原(CEA)检测在乳腺癌诊断和判断预后中的作用。方法应用免疫组化方法检测64例乳腺癌、37例正常及良性病变中癌胚抗原的表达。结果乳腺癌中癌胚抗原的阳性率(68.8%)明显高于正常对照组(16.2%),有显著性差异(P<0.05)。乳腺癌有淋巴结转移的癌胚抗原的阳性率(81.3%),略高于乳腺癌没有淋巴结转移的癌胚抗原的阳性率(56.3%),无显著性差异。结论癌胚抗原的检测有助于乳腺癌的诊断,癌胚抗原可能是判断乳腺癌预后的重要指标。     

Exo-focal postischemic neuronal damage in the rat brain: alteration of [H]forskolin binding using in vitro autoradiography

We studied the alteration of intracellular signal transduction using quantitative autoradiography of the second messenger system in order to clarify the mechanisms of delayed neuronal damage in the remote areas of rat brain after transient focal ischemia. Chronological changes of [³H]forskolin binding sites were measured to demonstrate the striatal-nigral pathway after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks and 4 weeks of recirculation. [³H]Forskolin binding sites were found to be markedly decreased in the lateral segment of the caudate putamen supplied by the occluded MCA after 90 min of ischemia with no recirculation. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, marked reduction of [³H]forskolin binding sites was observed in the ipsilateral substantia nigra which lay outside the ischemic areas. This postischemic delayed phenomenon observed in the substantia nigra developed concurrently with ⁴⁵Ca accumulation, which was detected there in our previous study. The delayed reduction of [³H]forskolin binding sites in the substantia nigra observed in the present study indicates that striatonigral terminal degeneration at presynaptic sites is caused by precedent ischemic damage of the ipsilateral caudate putamen and that exo-focal postischemic neuronal death is caused by a transsynaptic process associated with the ischemic foci.     

Validation of silver-stained nucleolar organizer regions for evaluation of invasive character of urinary bladder carcinoma in rats and mice

A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silverstained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P<0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas.     

ELISA检测襄虫病人血清循环抗原及其在疗效考核方面的应用

用快速双抗体夹心ＥＬＩＳＡ检测囊虫病人血清中的循环抗原，其阳性率为６７．５％；正常人血有的假阳性率为５．３３％；包虫、肝吸虫和弓形虫病人血清的交叉反应率分别为６．９％、７．５％和１２．５％。结果表明．该法与常规双抗体夹心ＥＬＩＳＡ相比具有较为敏感、快速、稳定和节省血清、试剂用量的优点，但其特异性有待进一步提高。用快速双抗体夹心ＥＬＩＳＡ和间接型ＥＬＩＳＡ检测第１至１０疗程囊虫病人血清中的循环抗原和抗体，表明检测循环抗原考核囊虫病人的治疗效果优于检测抗体     

Immunoglobulin heavy chain Diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement.
DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences.
Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen.
The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.     

Purification of antigenically intact Ro ribonucleoproteins; biochemical and immunological evidence that the 52-kD protein is not a Ro protein.

Anti-Ro sera immunoprecipitate Ro ribonucleoproteins (RNPs) from human cell extracts. Ro RNPs are biochemically heterogeneous particles whose functions are unknown and whose exact composition remains controversial. In addition to 60-kD Ro and to La proteins, a 52-kD polypeptide (p52) has been proposed to be a stable component of the Ro RNPs. To confirm the immunological studies supporting this hypothesis, we have biochemically purified Ro RNPs from HeLa cells using non-denaturing conditions. Ro RNPs segregated into three distinct populations, one of which only contained hY5 RNA (RohY5 RNPs). No p52 co-purified with Ro RNPs. Despite the absence of p52, purified Ro RNPs had biochemical and immunological properties identical to those of unfractionated Ro RNPs. Many anti-Ro sera only recognize p52 in immunoblots, and are said to be monospecific anti-p52. Preincubation with purified RohY5 RNPs (free of p52) of all human anti-Ro (including so-called monospecific anti-p52) sera abolished their capacity to immunoprecipitate Ro RNPs from unfractionated HeLa cell extracts. Conversely, preincubation of anti-Ro sera with purified p52 protein specifically inhibited recognition of p52 in immunoblots, but did not interfere with immunoprecipitation of Ro RNPs. Our data demonstrate that anti-p52 antibodies do not target intact Ro RNPs, nor do they target the native 60-kD Ro protein. Contrary to previous reports, p52 protein is not a stable component of antigenically intact Ro RNPs.