Src-type tyrosine kinase p56lck is critical for thymic stromal lymphopoietin-induced allergic rhinitis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. OBJECTIVE: Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. METHODS: The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies. RESULTS: Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. CONCLUSION: Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

Prevalence, risk factors, and impact on mortality of neuropsychiatric lupus: a prospective, single-center study.

Objective The objective of this paper is to identify the prevalence, risk factors, and impact on mortality of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Patients from the Hanyang BAE lupus cohort were registered and followed from 1998 to 2015. NPSLE was defined using American College of Rheumatology (ACR) case definitions and Ainiala criteria. Demographics, autoantibodies, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinic (SLICC)/ACR Damage Index were collected at baseline and then annually. Mortality data were derived by linking data from the Korean National Statistics Office. Multivariable logistic regression and Cox regression analysis were conducted in the inception cohort to assess the risk factors and mortality impact of NPSLE. Results Of 1121 registered patients, 429 (38.3%) had NPSLE manifestations according to ACR criteria and 216 (19.3%) by Ainiala criteria. In multivariable logistic regression analysis, higher SLEDAI (OR 1.08, CI 1.01-1.16, p = 0.02) and antiphospholipid antibody positivity (OR 1.72, CI 1.03-2.87, p = 0.04) at SLE diagnosis increased NPSLE risk, while elevated anti-dsDNA antibodies (OR 0.43, CI 0.24-0.78, p < 0.01) and greater education duration (OR 0.92, CI 0.85-1.00, p = 0.04) showed reduced risk of NPSLE. Cox proportional hazard models demonstrated that presence of NPSLE had a three-fold increased risk of mortality (HR 3.09, CI 1.03-9.21, p = 0.04), especially in patients with focal CNS NPSLE (HR = 7.83, CI 2.12-28.96, p < 0.01). Conclusion Higher SLEDAI, antiphospholipid antibody positivity, absence of anti-dsDNA antibody at SLE diagnosis, and fewer years of education are risk factors for development of NPSLE. Presence of NPSLE, especially focal CNS NPSLE, increased the risk of mortality in SLE patients.

Therapeutic effects of Artemisia scoparia Waldst. et Kitaib in a murine model of atopic dermatitis.

BACKGROUND: Artemisia scoparia Waldst. et Kitaib (AS) (Oriental wormwood, known as Bissuk in Korea) is a plant used in cosmetic and pharmaceutical treatments. However, the effect of AS on atopic dermatitis (AD) has not been described. AIM: To examine the inhibitory effect of AS on AD using a murine model. METHODS: We applied either AS, the butanol-extracted fraction of AS (Bu-OH) or 3,5-dicaffeoyl-epi-quinic acid (DEQA, a major component of Bu-OH) topically for 3 weeks to 2,4-dinitrofluorobenzene (DNFB)-induced skin lesions in BALB/c mice. RESULTS: AS, Bu-OH and DEQA suppressed the clinical symptoms of DNFB-induced skin lesions and he associated scratching behaviour. Numbers of inflammatory cells infiltrating skin lesions were significantly reduced by AS or Bu-OH application but not by DEQA. In addition, AS significantly suppressed serum levels of histamine and IgE, while Bu-OH significantly suppressed serum levels of histamine, IgE, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4 and IL-6, and DEQA significantly suppressed serum levels of histamine, IgE, TSLP and IL-4 in DNFB-induced AD mice. In skin lesions, AS and Bu-OH significantly reduced inflammatory cytokines, whereas DEQA did not. AS, Bu-OH and DEQA all significantly suppressed caspase-1 activities. CONCLUSIONS: These results demonstrate the anti-AD effects of AS, Bu-OH and DEQA, and suggest that all three have therapeutic potential.

Cholesterol Removal from Whole Egg by Crosslinked ß-Cyclodextrin.

This study was carried out to optimize cholesterol removal in whole egg using crosslinked ß-cyclodextrin (ß-CD) and to recycle the ß-CD. Various factors for optimizing conditions were concentration of the ß-CD, mixing temperature, mixing time, mixing speed and centrifugal speed. In the result of this study, the optimum conditions of cholesterol removal were 25% crosslinked ß-CD, 40°C mixing temperature, 30 min mixing time, 1,200 rpm mixing speed and 2,810×g centrifugal speed. The recycling was repeated five times. The cholesterol removal was 92.76% when treated with the optimum conditions. After determining the optimum conditions, the recyclable yields of the crosslinked ß-CD ranged from 86.66% to 87.60% in the recycling and the percentage of cholesterol removal was over 80% until third recycling. However, the cholesterol removal efficiency was decreased when the number of repeated recycling was increased. Based on the result of this study, it was concluded that the crosslinked ß-CD was efficient for cholesterol removal in whole egg, and recycling is possible for only limited repeating times due to the interaction of the ß-CD and egg protein.

Hyaluronidase treatment of acute lymphedema in a mouse tail model.

The purpose of this study was to investigate the impact of hyaluronidase (HAase) on lymphedema using an acute mouse tail lymphedema model. Six-week-old mice served to produce acute lymphedema and were then either treated with HAase injection or used as operative controls. An additional group of unmanipulated normal mice was used for comparison. Tail volumes were measured for 23 days and histological changes examined. Western blot analysis was conducted to quantify lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, podoplanin, CD 44, and vascular endothelial growth factor receptor3 (VEGFR3) expression levels. The operative control group showed an increase in thickness of the dermis and subdermis, microlymphatic dilatation, and an increase in neutrophils. In contrast, the HAase treated group exhibited alleviation of inflammation evidenced by a decline in microlymphatic dilatation and neutrophils and an overall increase in microlymphatic vessels. Western blot analysis demonstrated that TNF-alpha and TGF-beta1 expression declined but CD44 expression increased in the HAase treated group. Levels of LYVE1, podoplanin, and VEGFR3 also increased significantly in the HAase group. Our results indicate that HAase treatment in the acute mouse tail model reduced lymphedema volume possibly through degradation of HA trafficking, which reduced inflammation and fibrosis in tissues and stimulated lymphangiogenesis.

Theanine is a candidate amino acid for pharmacological stabilization of mast cells.

The increasing occurrences of allergic disorders may be attributed to exposure to environmental factors that contribute to the pathogenesis of allergy. The health benefits of green tea have been widely reported but are largely unsubstantiated. Theanine is the major amino acid present in green tea. In this study, we investigated the role of theanine in both IgE- and non- IgE-induced allergic response. Theanine inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling responses. IgE-mediated passive cutaneous anaphylaxis was inhibited by the oral administration or pharmaceutical acupuncture of theanine. Histamine release from mast cells was decreased with the treatment of theanine. Theanine also repressed phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced TNF-α, IL-1ß, IL-6, and IL-8 secretion by suppressing NF-κB activation. Furthermore, theanine suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. The current study demonstrates for the first time that theanine might possess mast cell-stabilizing capabilities.

Thiopental dose requirements for induction of anaesthesia and subsequent endotracheal intubation in patients with complete spinal cord injuries.

BACKGROUND: Dose requirements of thiopental depend on patient characteristics and infusion rate. We determined thiopental dose requirements for induction of anaesthesia, and the effects of remifentanil on cardiovascular and bispectral index (BIS) responses to tracheal intubation in spinal cord-injured (SCI) patients undergoing general anaesthesia. METHODS: Twenty patients with traumatic complete SCI undergoing elective surgery were enrolled. Twenty patients without SCI served as control. Anaesthesia was induced with thiopental, followed by remifentanil 1 µg/kg and rocuronium 0.8 mg/kg, and maintained with 2% sevoflurane and 50% nitrous oxide in oxygen after tracheal intubation. Thiopental was administered at a rate of 50 mg/15 s until abolition of the eyelash reflex. Thiopental doses, BIS values, systolic arterial blood pressure (SAP), heart rate (HR) and plasma catecholamine concentrations were measured. RESULTS: Total thiopental dose required to abolish the eyelash reflex based on total body weight (BW) (5.26 ± 0.87 vs. 3.91 ± 1.07 mg/kg, P < 0.001) or lean BW (6.56 ± 1.37 vs. 5.24 ± 1.36 mg/kg, P < 0.01) were significantly smaller in the SCI group than in the control. SAP was decreased by induction of anaesthesia with thiopental and remifentanil, and increased by tracheal intubation in both groups. However, the peak SAP after intubation was smaller in the SCI patients. HR increased significantly above baseline values following intubation in both groups with no significant intergroup differences. Hypertension was more frequent in the control group. Norepinephrine concentrations remained unaltered following intubation in both groups. CONCLUSIONS: These results suggest that the dose requirements of thiopental for induction of general anaesthesia and subsequent tracheal intubation are reduced in the SCI patients.

Preparation of encapsulated alliinase in alginate microparticles.

Alliinase (alkylsulphenate lyase, EC 4.4.1.4), which catalyses the production of allicin, was immobilized in alginate microparticles. Addition of pyridoxal 5'-phosphate to the microparticles enhanced alliinase activity. Encapsulated alliinase were significantly higher (30 and 22%, respectively) than those of non-encapsulated alliinase at 60°C and at pH 2. Therefore, microencapsulation of alliinase with alginate can offer an effective way of sustaining enzyme activity during oral administration and passage through the stomach.

Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression.

Histidine decarboxylase (HDC) catalyzes the formation of histamine from histidine. Histamine has various effects in physiological and pathological reactions, such as inflammation, cell growth, and neuro-transmission. We investigated the role of hypoxia-inducible factor (HIF)-1 on hypoxia-induced HDC expression in human mast cell line, HMC-1 cells and mouse bone marrow-derived mast cells (BMMCs). Hypoxia significantly increased histamine production. HDC expression and activity were induced by hypoxia. Additionally, when cells were transfected with a native form of HIF-1alpha, hypoxia could induce higher HDC expression than in the nontransfected cell. HIF-1 binding activity for HDC 5' flanking region (HFR) was similar to that for the hypoxia-responsive element. Using HDC promoter deletion analysis, we also demonstrated that HFR was regulated by HIF-1 activation. In addition, depletion of HIF-1alpha prevents hypoxic induction of HDC in BMMCs. In conclusion, these results demonstrate that hypoxia induces HDC expression by transcriptional mechanisms dependent upon HIF-1.

IgG nephropathy - confusion and overlap with C1q nephropathy.

BACKGROUND: IgG nephropathy is one of the most recently described glomerulopathies, which frequently overlaps with C1q nephropathy. To clarify this entity, we evaluated renal biopsy cases with IgG deposits as a sole or predominant immunoglobulin. METHODS: Fourteen cases demonstrating IgG as a predominantly deposited immunoglobulin in patients without infectious or autoimmune diseases between 1997 and 2008 were studied. Twelve patients had glomerular disease in the native kidney and the other 2 were renal allograft recipients. RESULTS: Clinical presentation was microscopic hematuria, proteinuria, or both and nephrotic syndrome was observed in 3 patients. Segmental glomerulosclerosis was observed in 4 patients and mesangial hypercellularity was present in 7. Tubulointerstitial changes were not evident except for allograft biopsies. On immunofluorescence, mesangial or capillary wall IgG deposits were present in all cases, and C1q was observed in 11 cases in a similar pattern with IgG, co-dominant in 5 cases and dominant in 1. CONCLUSIONS: Since a significant overlap is frequently observed in these two rare conditions, we suggest a tentative diagnosis of IgG/C1q nephropathy in such cases.

Toll-like receptor expression in patients with renal allograft dysfunction.

Toll-like receptor (TLR) is known to be a mediator of innate immunity, but recent reports have shown that TLR provides a link to adaptive immunity involved in allograft rejection. To explore the expression patterns in various conditions of renal transplantation, we examined TLR subunit mRNA expressions in renal allograft biopsies of acute rejection (AR; n = 11), chronic rejection (CR; n = 15), chronic cyclosporine nephrotoxicity (CsAN; n = 22), and immunoglobulin A nephropathy (IgAN; n = 9) patients. Control tissues (n = 7) were obtained from normal renal cortical tissue of renal cell carcinoma patients. The diagnosis was made according to the Banff 97 classification. The expressions of TLR 2, 3, 4, and 9 mRNA were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) using SYBR green. Statistical analysis was performed using analysis of variance (ANOVA) and the Student t test. TLR 2 and 3 mRNA expressions were not significantly different in any group (P > .05). In contrast, TLR 4 mRNA expression was significantly increased in all allograft groups compared with that of controls, and significantly higher in the CsAN than other transplant groups (P < .05). TLR 9 mRNA expression was up-regulated in CsAN and IgAN compared with AR and CR (P < .05). These results suggested that TLR4 mRNA expression was increased in renal allograft patients with chronic allograft dysfunction. Further studies are needed to correlate TLR subtypes with various causes of graft dysfunction among renal allograft patients.

Long-Term Outcomes of Patients with Stent Tips Embedded into Internal Carotid Artery Branches during Aneurysm Coiling.

BACKGROUND AND PURPOSE: During stent-assisted coiling of ICA aneurysms, stent tips are sometimes unintentionally embedded into ICA branches. Stent tips can be visualized because they have radiopaque markers. Concerns regarding stent tip misplacement include risks of artery perforation and occlusion. The aim of this study was to evaluate the long-term outcomes of ICA branches with embedded stent tips. MATERIALS AND METHODS: ICA branches with embedded stent tips were identified among 35 patients with unruptured ICA aneurysms treated with stent-assisted coiling between November 2003 and November 2014. Patient clinical and angiographic outcomes associated with the embedded stent tip were analyzed. RESULTS: Most of the 35 studied aneurysms were paraclinoid ICA aneurysms (n = 30). The most commonly involved ICA branch was the posterior communicating artery (26 patients, 74.3%), followed by the anterior choroidal artery (8 patients, 22.9%) and ophthalmic artery (1 patient, 2.9%). During the follow-up period (38.6 ± 17.9 months), no new neurologic deficits developed. Neither hemorrhagic nor thromboembolic events occurred. Angiography was performed during the final follow-up evaluation at a mean of 32.7 ± 18.0 months, and all ICA branches with embedded stent tips showed patent blood flow without severe luminal narrowing. CONCLUSIONS: In our experience, placement of a stent tip into ICA branches during stent-assisted coiling was not associated with any major adverse events.

Clinical Significance of Macrophage Polarization in Antibody-Mediated Rejection of Renal Allograft.

BACKGROUND: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. METHODS: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival. RESULTS: The glomerular M2 polarization group showed significantly higher chronic glomerulopathy scores, serum creatinine levels, and lower eGFR at the time of biopsy (P = .019 and P = .015, respectively) and 3-month postbiopsy (P = .016 and P = .032, respectively) than the M1 polarization group. The tubulointerstitial M2 polarization group had significantly lower glomerulitis, arteritis, peritubular capillaritis, and glomerulitis + peritubular capillaritis scores than the M1 polarization group, but there was no significant difference in renal function. Long-term graft survival was not associated with macrophage polarization. CONCLUSION: Glomerular M2 polarization in ABMR biopsy samples is associated with chronic glomerular injury and poorer graft function, but without graft survival.

Piriformis ganglion: An uncommon cause of sciatica.

UNLABELLED: Sciatica can occur due to a spinal lesion, intrapelvic tumor, diabetic neuropathy, and rarely piriformis syndrome. The causes of piriformis syndrome vary by a space-occupying lesion. A ganglionic cyst can occur in various lesions in the body but seldom around the hip joint. In addition, sciatica due to a ganglionic cyst around the hip joint has been reported in one patient in Korea who underwent surgical treatment. We experienced two cases of sciatica from a piriformis ganglionic cyst and we report the clinical characterics and progress after non-operative treatment by ultrasonography-guided aspiration. The two cases were diagnosed by magnetic resonance imaging and were treated by ultrasonography-guided aspiration. We followed the patients for more than 6months. The symptoms of piriformis syndrome from the ganglion improved following aspiration and this conservative treatment is a treatment method that can be used without extensive incision or cyst excision. LEVEL OF EVIDENCE: Level IV historical case.

Significance of Time-Zero Biopsy for Graft Renal Function After Deceased Donor Kidney Transplantation.

BACKGROUND: Donor organ quality from deceased donors affects graft survival after kidney transplantation. This study was performed to identify clinico-histological factors that affect early graft outcome, using time-zero biopsies of deceased donors. METHODS: Between December 2006 and July 2011, 135 recipients of deceased donor kidneys were included, and data concerning donor and recipient-related clinical characteristics and histological findings of time-zero biopsies categorized by use of the Banff 07 scoring system were included in the analysis. Mean donor age was 44.3 ± 12.3 years. Mean terminal serum creatinine level and cold ischemic time were 1.50 ± 0.96 mg/dL and 349 ± 166 minutes. Mean follow-up time after transplantation was 37 ± 16 months, and all recipients were followed for at least 1 year. RESULTS: Global glomerulosclerosis (38.5%), tubular atrophy (37.8%), arteriolar hyaline thickening (25.9%), interstitial fibrosis (23%), vascular fibrous intimal thickening (21.5%), and interstitial inflammation (20%) were the major pathologic findings of time-zero biopsies. The majority of pathologic scores were of mild degree. Among histological findings, arteriolar hyaline thickening and interstitial fibrosis were only significantly associated with early post-transplant renal function in multivariate analyses. CONCLUSIONS: Considerations of clinico-histological findings were found to be valuable for predicting early graft outcome after deceased donor kidney transplantation.

Concurrent Post-Transplantation Diabetes Mellitus in Renal Allograft Recipients With Immunoglobulin A Nephropathy.

BACKGROUND: The prevalence of post-transplantation immunoglobulin A nephropathy (PTIgAN) and diabetes mellitus (PTDM) increases with time after transplantation, and recognition and management of these conditions is becoming more important in renal allograft recipients as graft survival increases. METHODS: We explored the influence of concurrent PTDM on renal allograft histology and function in 111 cases with PTIgAN diagnosed from 2000 to 2010 at our institution. RESULTS: Sixteen patients (14.4%) had PTDM at the time of diagnosis of PTIgAN, which increased to 28 patients (25.2%) at the last follow-up (10.4 years after transplantation). Donor ages were younger in PTIgAN patients with concurrent PTDM. However, other clinical and demographic data were not significantly different between PTIgAN patients with and without PTDM. Histologically, Banff "mm" scores were higher and "M1" of the Oxford classification was more frequent in PTIgAN patients with concurrent PTDM than in patients without PTDM, but the difference did not reach statistical significance. Serum creatinine levels and proteinuria at the time of biopsy and overall graft survival did not vary according to the presence of PTDM both at biopsy and at the last follow-up. CONCLUSIONS: Concurrent PTDM does not significantly influence graft function or outcome for 10 years after transplantation in PTIgAN patients.

Contribution of the Na-K-Cl cotransporter on GABA(A) receptor-mediated presynaptic depolarization in excitatory nerve terminals.

GABA(A) receptor-mediated responses manifest as either hyperpolarization or depolarization according to the intracellular Cl(-) concentration ([Cl(-)](i)). Here, we report a novel functional interaction between the Na-K-Cl cotransporter (NKCC) and GABA(A) receptor actions on glutamatergic presynaptic nerve terminals projecting to ventromedial hypothalamic (VMH) neurons. The activation of presynaptic GABA(A) receptors depolarizes the presynaptic nerve terminals and facilitates spontaneous glutamate release by activating TTX-sensitive Na(+) channels and high-threshold Ca(2+) channels. This depolarizing action of GABA was caused by an outwardly directed Cl(-) driving force for GABA(A) receptors; that is, the [Cl(-)](i) of glutamatergic nerve terminals was higher than that predicted for a passive distribution. The higher [Cl(-)](i) was generated by bumetanide-sensitive NKCCs and was responsible for the GABA-induced presynaptic depolarization. Thus, GABA(A) receptor-mediated modulation of spontaneous glutamatergic transmission may contribute to the development and regulation of VMH function as well as to the excitability of VMH neurons themselves.

Role of mesangial fibrinogen deposition in the pathogenesis of crescentic Henoch-Schonlein nephritis in children.

AIMS: To clarify the role of mesangial fibrinogen deposition in crescentic Henoch-Schönlein nephritis (HSN). METHODS: A retrospective analysis of 21 children with HSN treated with immunosuppressants. Serial renal biopsies were performed before and after treatment. They were divided into two groups according to the immunofluorescent course of fibrinogen deposition: group I (n = 9), no or decreased deposition; group II (n = 12), persistent or increased deposition. RESULTS: There were no differences between the two groups in renal manifestations or laboratory and histological findings at presentation. However, the activity index after immunosuppressive treatment was significantly decreased in group I (mean, 7.9 (SEM, 0.7) v 2.9 (0.4); p = 0.008) and unchanged in group II (mean, 6.8 (SEM, 0.3) v 6.0 (2.1)). The chronicity index was unchanged in group I, but increased in group II (mean, 0.8 (SEM, 0.3) v 1.8 (0.3); p = 0.02). Univariate analysis revealed that the only factor significantly related to persistent or increased fibrinogen deposition was age more than 9 years (p = 0.03). Furthermore, the intensity of fibrinogen deposition at the second biopsy correlated positively with the age at onset (R2= 0.306; p = 0.009) and changes in the percentage of crescents (post-treatment crescents (%) minus pretreatment crescents (%)) correlated positively with the intensity of fibrinogen deposition at the second biopsy (R2= 0.193; p = 0.046). CONCLUSIONS: This study indicates that fibrinogen deposition has an important role to play in renal injury of crescentic HSN and reflects persistent severe histological activity.

Immunohistochemical analysis of infiltrating inflammatory cells in the isolated v-lesion of allograft kidney.

The term "isolated v-lesion" was proposed at the 2009 Banff conference on allograft pathology. It is still debated whether the isolated v-lesion is a part of the antibody-mediated or T cell-mediated rejection and whether the isolated v-lesion has any prognostic significance of its own. To investigate the characteristics of the isolated v-lesion, we identified infiltrating inflammatory cells in renal allograft biopsy specimens with these lesions. We selected 11 allograft renal biopsy specimens which were compatible with the original definition of the isolated v-lesion (v1 or v2 with i ≤ 1 and t ≤ 1) and had enough paraffin-embedded tissue for immunohistochemistry. We performed immunohistochemistry for markers of T cells (CD3, CD4, and CD8), B cells (CD20), NK/T cells (CD56), and macrophages (CD68). The number of positive cells was counted in each compartment of the renal tissue including the arteries, peritubular capillaries, glomeruli, tubules, and interstitium. Arteries were infiltrated by CD3/CD8-positive T cells and CD68-positive macrophages. Three cases showed T cell-dominant infiltrates and four cases showed macrophage-dominant infiltrates. Glomeruli showed a similar inflammatory cell profile to that of arteries. Tubulitis was composed of CD3/CD8-positive T cells. The components of interstitial inflammation were more variable with the presence of CD20-positive B cells. In six cases, interstitial infiltrates were predominantly composed of CD3/CD8-positive T cells, and two of these cases showed almost exclusive infiltrates of T cells. However, four cases showed co-dominant infiltrates of T and B cells, and one case showed predominant B cell infiltrates. The isolated v-lesion has a heterogeneous pathogenesis, and B cell-predominant infiltrates in some cases suggest that this lesion could be related to an antibody-related process.

5-HT1A receptor-mediated activation of G-protein-gated inwardly rectifying K+ current in rat periaqueductal gray neurons.

5-hydroxytryptamine (5-HT) has been reported to modulate analgesia produced by opioids or electrical stimulation of the periaqueductal gray (PAG). 5-HT increases K+ conductance and inhibits the firing activity of the PAG neurons. We examined the electrophysiological and pharmacological characteristics of the K+ current involved in 5-HT-induced hyperpolarization of dissociated rat PAG neurons. Among the neurons tested, 5-HT activated inward K+ currents in 30-40%, whilst the remaining 60-70% did not respond to 5-HT. 5-HT activated an inwardly rectifying K+ current (I5-HT) in a concentration- and voltage-dependent manner. I5-HT was mimicked by a 5-HT1A receptor selective agonist, 8-OH-DPAT, and was reversibly blocked by a 5-HT1A receptor antagonist, piperazine maleate, but not by a 5-HT2 receptor antagonist, ketanserin. I5-HT was sensitive to K+ channel blockers such as quinine and Ba2+, but insensitive to 4-aminopyridine, Cs+ and tetraethylammonium. I5-HT was inhibited by GDP(beta)s and was irreversibly activated by GTP(gamma)s. I5-HT was significantly suppressed by N-ethylmaleimide and pertussis toxin, but not by cholera toxin. Second messenger modulators such as staurosporin, forskolin, and phorbol-12-myristate-13-acetate did not alter I5-HT. The present study indicates that 5-HT-induced hyperpolarization of the PAG neurons results from activation of the pertussis toxin-sensitive G-protein-coupled inwardly rectifying K+ currents through 5-HT1A receptors.