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Reliable markers for the rapid discrimination of severe renal damage remain a vital concern for lupus nephritis (LN). To determine a better tool for kidney damage detection, the present study compared the evaluation ability of novel urinary cytokines and chemokines (namely urinary monocyte chemoattractant protein 1 (uMCP-1), tumor necrosis factor-like weak inducer of apoptosis (uTWEAK)) with traditional serum or urinary markers (namely urinary alpha 1-microgrobulin (uα1-MG), beta 2-microglobulin (uβ2-MG) and serum complement C3 (C3), complement C4 (C4), creatinine (Cr), blood urea nitrogen (BUN) and cystatin C (Cys C)) in discriminating LN renal damage. Correlations between markers with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) renal SLEDAI scores, biopsy activity index (BAI) and biopsy chronicity index (BCI) scores were evaluated. Receiver operating characteristic (ROC) curves were generated to evaluate a single or combined model in discriminating active renal involvement (rSLEDAI scores 0) and patients with poor pathological outcome (BAI scores ≥ 7). uMCP-1 and uTWEAK possess higher correlation coefficients with renal damage and larger areas under ROC curves (AUCs) than other markers. A combined model of uMCP-1 and uTWEAK showed an AUC of 0.887, sensitivity of 86.67% and specificity of 80.00% to discriminate active LN, and an AUC of 0.778, sensitivity of 75.00% and specificity of 81.82% to discriminate LN with poor outcome, which are better than the utility of any markers individually.

The International Society of Blood Transfusion Working Party on red cell immuno-genetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.

The rapid conversion of the i to the I phenotype on postnatal red blood cells (RBCs) reflects the elaborate functions of cell surface branched-chain I antigenic structure. The adult i phenotype has been noted to be partially associated with congenital cataracts. These phenomena make the molecular genetics of the blood group I system and the regulation mechanism for I antigen expression in postnatal RBCs intriguing. It has been demonstrated that the human I locus expresses three IGnT forms, designated IGnTA, IGnTB, and IGnTC, which have different exon 1, but identical exons 2 and 3, coding regions. The uncommon molecular genetics of the I locus offers a new perspective of the formation and expression of the I antigen in different cells, and provides an insight into the questions derived from investigation of the adult i phenotype. The results obtained from molecular analysis of two adult i groups, with and without congenital cataracts, support the proposed molecular mechanism for the partial association of the two traits, namely that mutations that lead to the production of mutant IGnTC only, may result in an adult i phenotype but not congenital cataracts, whereas mutation events that occur in the common exon 2 or exon 3 regions, which result in the elimination of the activity of all three IGnT enzymes, would seem to lead to the development of both traits. This suggests that an I-gene defect may lead directly to the development of congenital cataracts. However, the result of the gene knock-out mouse model does not confirm this suggestion. Analysis of the regulation for I antigen expression shows that i-to-I phenotypic transition during erythroid differentiation is regulated by the transcription factor CCAAT/enhancer binding protein α (C/EBPα), which enhances transcription of the IGnTC gene, consequently leading to the formation of the cell surface I antigen. Subsequent investigation further showed that phosphorylation of the Ser-21 residue on C/EBPα blocks C/EBPα activity on IGnTC gene induction, while dephosphorylation of C/EBPα Ser-21 occurs in both the granulopoietic and erythropoietic processes, leading to stimulation of IGnTC gene expression and consequently I antigen formation. These results demonstrate that the formation of I antigen during the development of erythrocytes, and also granulocytes, is determined by a mechanism that is known to be crucial to determining granulopoiesis, namely involvement of the transcription factor C/EBPα and Ser-21 dephosphorylation of this protein.

We previously reported that vanilloid receptor type 1 (VR1, or TRPV1) was up-regulated in dorsal root ganglion (DRG) and the spinal dorsal horn after chronic inflammatory pain produced by complete Freund's adjuvant (CFA) injection into the plantar of rat hind paw. In the present study, we found that subcutaneous or intrathecal application of capsazepine (CPZ), a TRPV1 competitive antagonist, could inhibit thermal hyperalgesia on day 1 and on day 14 but not on day 28 after CFA injection. With extracellular electrophysiological recording, the effect of CPZ on noxious electrical or heat stimulation evoked responses of wide dynamic range (WDR) neurons in the deep layers of the spinal dorsal horn was evaluated. Under noxious electrical stimulation to sciatic nerve, CPZ applied to the spinal cord produced an inhibition on Adelta- and C-fiber evoked responses of WDR neurons on day 1 and 14, but not on day 28. Under radiant heat stimulation to the receptive field skin, subcutaneous application of CPZ significantly inhibited the background activity and extended the response latency of WDR neurons on day 14. These results provide new evidence for the functional significance of TRPV1 at the early stage, but not the late stage, in the rat model of CFA-induced inflammatory pain.

Background: The present study aims to investigate the role of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons in chronic pain including thermal hyperalgesia and mechanical allodynia. Chronic inflammatory nociception of rats was produced by intraplantar injection of complete Freund's adjuvant (CFA) and data was collected until day 28 following injection. Results: Thermal hyperalgesia was evident from day 1 to day 28 with peak at day 7, while mechanical allodynia persisted from day 1 to day 14 and was greatest at day 7. Intrathecal administration of AMG 9810 at day 7, a selective TRPV1 antagonist, significantly reduced thermal hyperalgesia and mechanical allodynia. TRPV1 expression in DRG detected by Western blotting was increased relative to baseline throughout the observation period. Double labeling of TRPV1 with neuronal marker neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4) was used to distinguish different subtypes of DRG neurons. TRPV1 expression was increased in the medium-sized myelinated A fiber (NF200 positive) neurons and in small non-peptidergic (IB4 positive) neurons from day 1 to day 14 and was increased in small peptidergic (CGRP positive) neurons from day 1 to day 28. Conclusion: TRPV1 expression increases in all three types of DRG neurons after CFA injection and plays a role in CFA-induced chronic inflammatory pain including thermal hyperalgesia and mechanical allodynia.

The central nucleus of amygdala (CeA) plays an important role in pain regulation. Calcitonin gene-related peptide (CGRP)-like immunoreactive fibers and CGRP receptors are distributed densely in CeA. The present study was performed to elucidate the role of CGRP in nociceptive regulation in the CeA of rats. Intra-CeA injection of CGRP induced dose-dependent increases in the hind-paw withdrawal latency tested by hotplate test and Randall Selitto Test, indicating an antinociceptive effect of CGRP in CeA. Furthermore, the antinociceptive effect of CGRP was blocked by intra-CeA administration of the CGRP receptor antagonist CGRP8-37, suggesting that CGRP receptor1 is involved in the CGRP-induced antinociception. The CGRP-induced antinociception was attenuated by s.c. injection of the opioid antagonist naloxone, suggesting an involvement of endogenous opioid systems in CGRP-induced antinociception. Moreover, it was demonstrated that opioid receptors in the periaqueductal gray, but not in CeA, contributed to the CGRP-induced antinociception, indicating the importance of the pathway between CeA and the periaqueductal gray in CGRP-induced antinociception. Combining retrograde fluorescent tracing with immunohistochemistry, we found that met-enkephalinergic neurons were innervated by CGRP-containing terminals in CeA. Furthermore, most neurons in the CeA retrogradely traced from the periaqueductal gray were contacted by CGRP-containing terminals and some of them were surrounded by characteristic basket-like structures formed by the terminals, suggesting that CGRP innervates the neurons which project from CeA to the periaqueductal gray. The results indicate that CGRP activates the met-enkephalinergic neurons, which project from CeA to the periaqueductal gray, producing antinociceptive effect in rats.

The present study was performed in rats with experimentally induced mononeuropathy after left common sciatic nerve ligation. The hindpaw withdrawal latencies to thermal and mechanical stimulation increased significantly after intra-periaqueductal grey injection of 2 or 3 nmol, but not 1 nmol of galanin in rats with mononeuropathy. Intraperitoneal administration of 4.5 mg/kg morphine induced significant increases in hindpaw withdrawal latencies to both noxious stimulation, which were attenuated by following intra-periaqueductal grey injection of 2 nmol of the galanin antagonist galantide. Furthermore, the antinociceptive effect induced by intra-periaqueductal grey injection of 26.6 nmol of morphine was attenuated significantly by following intra-periaqueductal gray administration of 2 nmol of galantide. The results demonstrated that in periaqueductal grey galanin plays an antinociceptive role in rats with mononeuropathy and galanin is involved in the mechanisms of opioid-induced antinociception.

Objective: To compare the measurement of quantitative DNA in squamous cell carcinoma of the head and neck by flow cytometry and image cytometry. Design: Comparison of image cytometry to the more commonly used flow cytometry using paraffin-embedded tissues. Setting: University of California, Davis Medical Center, Sacramento. A 472-bed university teaching hospital. Patients: Records of 26 patients with squamous cell carcinoma of the tongue, base of tongue, and larynx were obtained from the case files of an otolaryngologist–head and neck surgeon. They were reviewed for staging and follow-up. Results: We demonstrated a 96% concordance rate between the methods. A solitary discrepant case was aneuploid by image cytometry and diploid by flow cytometry. The specimen involved tumor infiltrated by lymphocytes that may have masked the aneuploid population to measurement by flow cytometry. Quantitative DNA analysis correlated moderately well with tumor grade, tumor stage, and patient outcome with a minimum of 6 years of follow-up. All patients with diploid tumors were long-term survivors. Conclusions: Both methods provide accurate quantitative DNA analyses in squamous cell carcinoma of the head and neck. The methods are highly correlative and yield similar predictive data regarding tumor behavior and prognosis. (Arch Otolaryngol Head Neck Surg. 1994;120:294-297)

Fluorescence in situ hybridization (FISH) was applied to detect the copy number of the retinoblastoma (RB1) tumor suppressor gene in metaphase chromosomes and interphase nuclei. We used 14 λ phage clones spanning the whole RB1 gene region as a probe and obtained a specific hybridization signal in normal metaphase chromosomes at 13q14. Normal interphase nuclei showed two RB1 signals in about 90% of cases, whereas two cell lines with cytogenetically defined deletions involving the RB1 gene showed only one hybridization signal in about 80% of the nuclei. Analogous changes were detected in metaphase chromosomes. Multicolor FISH with subsets of the phage clones allowed visualization of subregions within the 200-kb gene in interphase nuclei. Analysis of clinical breast cancer samples showed that most of the cells contained two copies of the RB1 gene, even when restriction fragment length polymorphism analysis showed loss of heterozygosity (LOH) at the RB1 locus. This indicates that LOH at the RB1 locus in breast cancer cells probably involves mechanisms other than physical deletion.

The committee met in Macao Special Administrative Region,China, during the 2008 International Society of Blood Trans-fusion (ISBT) Congress. Some changes to the classificationdocumented in Blood Group Terminology 2004 [1] and updatedin 2007 [2] were agreed and are described below. The fullupdated classification can be found on the blood groupterminology website at http://www.blood.co.uk/ibgrl. A newblood group system, the RHAG system, was established andnew antigens were added to the Rh, Kell, and Dombrocksystems (Table 1). A total of 308 antigens are now recognized,270 of which are clustered in 30 blood group systems.

Studies have shown that 5-hydroxytryptamine (5-HT) plays an important role in the descending pathway of pain modulation from brainstem to the spinal cord. Using selective 5-HT receptor antagonists, the present study investigated which type of 5-HT receptor(s) in the spinal cord was involved in the morphine-induced anti-nociception in intact rats, in rats with nerve injury and in rats with inflammation. The hindpaw withdrawal latencies decreased significantly after sciatic nerve injury and hindpaw inflammation compared with intact rats. Intrathecal administration of 25 or 10 μg of the selective 5-HT 1A recepter antagonist spiroxatrine, but not 1 μg of spiroxatrine, significantly blocked the increased hindpaw withdrawal latencies to thermal and mechanical stimulation induced by intra-periaqueductal gray injection of 1 μg of morphine in intact rats. Intrathecal injection of the 5-HT 2 receptor antagonist RS 102221 and the 5-HT 3 receptor antagonist MDL 72222 had no significant effects on the increased hindpaw withdrawal latencies to both noxious stimulations induced by intra-periaqueductal gray injection of morphine. Furthermore, intrathecal administration of spiroxatrine, but not RS 102221 nor MDL 72222, significantly attenuated the increased hindpaw withdrawal latencies induced by intra-periaqueductal gray administration of morphine in rats with nerve injury and in rats with inflammation. The results demonstrate that the 5-HT 1A receptor, not 5-HT 2 nor 5-HT 3 receptor, plays an important role in the descending pathway of anti-nociception from the brainstem to the spinal cord in intact rats, in rats with nerve injury and in rats with inflammation.

The role of nociceptin, the endogenous ligand for the opioid receptor-like (ORL1) receptor, in nociceptive processing is controversial. Most studies demonstrate hyperalgesia following supraspinal administration, analgesia following intrathecal and peripheral administration at higher doses, and hyperalgesia following intrathecal and peripheral application at lower doses. The present study investigates the effect of nociceptin on synovial plasma extravasation and its ability to modulate 5-hydroxytryptamine-induced synovial plasma extravasation using the rat knee joint model of inflammation. Nociceptin alone does not alter synovial plasma extravasation from baseline. Nociceptin at concentrations up to 1 nM enhances 5-hydroxytryptamine-induced synovial plasma extravasation (up to 50%) and nociceptin at concentrations above 100 nM inhibits 5-hydroxytryptamine-induced synovial plasma extravasation (down to 45%). The novel, selective ORL1 receptor antagonist J-113397 potently inhibits the pro-inflammatory effect of nociceptin, but only partly inhibits, at higher concentrations, the anti-inflammatory effects of nociceptin. These findings demonstrate a dose-dependent bi-directional effect of nociceptin on inflammatory processes and may indicate a target for novel therapeutics.

Massage-like stroking induces acute antinociceptive effects that can be reversed by an oxytocin antagonist, indicating activation of oxytocin on endogenous pain controlling systems. We now demonstrate an increase in hindpaw withdrawal latencies (HWLs), in response to thermal and mechanical stimuli, which was present after six treatments of massage-like stroking every other day and which continued to increase through the remaining seven treatments. Repeated massage-like stroking also resulted in increased oxytocin-like immunoreactivity (oxytocin-LI) levels in plasma and periaquaductal grey matter (PAG). Furthermore, increases in HWLs were also present after injections of oxytocin into the PAG (0.1, 0.5 and 1.0 nmol). Intra-PAG oxytocin injection of 1 nmol followed by 1 or 20 nmol of naloxone attenuated the increments in HWL. Also, there was a dose-dependent attenuation of the oxytocin-induced antinociceptive effects following intra-PAG injection of the µ-opioid antagonist β-funaltrexamine (β-FNA) and the κ-opioid antagonist nor-binaltorphimine (nor-BNI) but not the δ-antagonist naltrindole. The long-term antinociceptive effects of massage-like stroking may be attributed, at least partly, to the oxytocinergic system and its interaction with the opioid system, especially the µ- and the κ-receptors in the PAG.

The present study was performed in rats with experimental mononeuropathy after left common sciatic nerve constriction. A bilateral decrease in hindpaw withdrawal latency to thermal and mechanical stimulation was observed after unilateral ligation of the left common sciatic nerve; however, it was more pronounced on the lesioned side. Compared with sham-operated rats, the content of calcitonin gene-related peptide-like immunoreactivity was significantly decreased in the left dorsal horn of the spinal cord and left dorsal root ganglia in rats with mononeuropathy. Blocking the receptor of calcitonin gene-related peptide, by intrathecal injection of 5 or 10 nmol of calcitonin gene-related peptide (8–37), induced a significant bilateral increase in hindpaw withdrawal latency to both thermal and mechanical stimulation which, however, was significantly less pronounced in mononeuropathic rats than in intact rats. The effect of calcitonin gene-related peptide (8–37) was reversed by intrathecal administration of the opioid antagonist naloxone. The contribution of calcitonin gene-related peptide and its receptors to transmission of presumed nociceptive information appears to be reduced in the sciatic nerve constriction model. The decrease in reflex responsiveness induced by calcitonin gene-related peptide (8–37) was counteracted by naloxone, indicating that opioids control the net effect of excitation in the spinal cord circuitry induced by calcitonin gene-related peptide and possibly other co-released neurotransmitters.

The Tupaia belangeri yunalis (tree shrew) is one of the primitive primates. They were inoculated subcutaneously in the footpad or intravenously with Mycobacterium leprae from a patient with multibacillary leprosy. As controls, the footpads of CFW mice were inoculated with the same suspension of M. leprae. The results showed growth of acid-fast bacilli (AFB) in the footpads of locally inoculated CFW mice and in the footpads of both locally and intravenously inoculated tupaias. Whereas the numbers of AFB declined in the footpads of CFW mice after 12 months, they increased in the tupaia footpads, up to 2.44 x 19(9) AFB/g of tissue. The footpads of one tupaia were swollen, which on section revealed a granulomatous infiltration, including foamy and heavily infected macrophages. M. leprae were also seen in the branches of cutaneous nerves. Also AFB occurred in some viscera. Preliminary studies indicate that the AFB multiplying in tupaias are M. leprae.