Left ventricular outflow tract obstruction caused by a congenital accessory mitral valve leaflet and treated by open-heart surgery in a young dog.

A 3-month-old Shetland sheepdog presented with a loud ejection murmur and exercise intolerance. Echocardiography revealed an accessory mitral valve leaflet, characterised by a valve-like structure separate from the mitral valve seen in the subaortic region of the ventricular septum. The left ventricular outflow tract was partially obstructed with a pressure gradient of 12 mmHg. Accessory mitral valve leaflet resection and mitral valvuloplasty were performed during open-heart surgery. Histology performed on the membrane-like structures were indicative of fibrous connective tissues. Postoperative echocardiography confirmed removal of the valve-like structure with resolution of the left ventricular outflow tract obstruction. The pressure gradient was decreased to 4.6 mmHg. The dog was in good condition and no further treatment was required 5 months after surgery. Both cardiac troponin I and NT-proBNP were markedly decreased. In this dog, surgical resection combined with mitral valve plasty resolved the left ventricular outflow tract obstruction and the clinical signs.

The outcome of surgical mitral valve repair with loop-in-loop technique in dogs with different stage myxomatous mitral valve disease.

OBJECTIVES: Surgical mitral valve repair is a possible option for dogs with myxomatous mitral valve disease. However, information on surgical results and postoperative echocardiography is limited. This study aimed to verify the stage-specific surgical results of mitral valve repair and postoperative echocardiographic changes for two years following surgery. ANIMALS: Adult dogs (n = 55) treated with surgical mitral valve repair using the loop-in-loop technique were included in this study. Medical records were retrospectively reviewed. RESULTS: Ninety percent of cases (50/55) survived to discharge, which survival was significantly decreased in myxomatous mitral valve disease advanced-stage dogs, Stage B2 (n = 14): 100%, Stage C (n = 27): 96.2%, and Stage D (n = 14): 71.4%. Significant reductions of overall heart size (vertebral heart score: preoperative 11.4 vs. post one month 10.2, P < 0.001), left atrium (left atrium to aortic root ratio: preoperative 2.3 vs. post one month 1.5, P < 0.001) and left ventricle (left ventricular end-diastolic diameter [normalized for bodyweight]: preoperative 2.2 vs. post one month 1.5, P < 0.001) were documented one month after surgery, showing successful management of mitral regurgitation. All medications for mitral valve disease were discontinued three months after surgery. The recurrence of mitral regurgitation was not evident during the two-year follow-up period. CONCLUSIONS: Surgical mitral valve repair with the loop-in-loop technique is associated with significant decreases in indices of cardiac size at one-month post-repair. Disease stage influences operative survival after surgical mitral valve repair.

Monitoring of hemostatic abnormalities in major orthopedic surgery patients treated with edoxaban by APTT waveform.

INTRODUCTION: An analysis of the activated partial thromboplastin time (APTT) in major orthopedic surgery patients receiving edoxaban for the prevention of venous thromboembolism (VTE) was carried out. METHODS: The APTT waveform was analyzed in the above patients to monitor edoxaban administration. RESULTS: Of these 99 patients, 12 exhibited deep vein thrombosis, and 25 had massive bleeding. An increased biphasic pattern of the APTT waveform was observed after the administration of edoxaban, but there were no significant differences between the patients with and without complications. The peak times of acceleration, velocity, and 1/2 fibrin formation were significantly prolonged after the administration of edoxaban, especially in patients with massive bleeding, and were moderately correlated with the anti-Xa activity. While the heights of velocity and acceleration peak 2 were lower in patients receiving warfarin treatment than in those receiving edoxaban, the widths of these parameters were significantly longer. The height of 1/2 fibrin formation and the width of acceleration peaks 1 and 2 and the velocity were significantly increased after the administration of edoxaban. CONCLUSION: The peak time of the APTT waveform was significantly prolonged after the administration of edoxaban. The analysis of the APTT waveform may therefore be useful for the prediction of the risk of massive bleeding.

Antimelanoma differentiation-associated protein 5 antibody level is a novel tool for monitoring disease activity in rapidly progressive interstitial lung disease with dermatomyositis.

BACKGROUND: Antimelanoma differentiation-associated protein (anti-MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). OBJECTIVES: We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. METHODS: Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti-MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide. RESULTS: All patients achieved RP-ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti-MDA5 antibody levels at remission. Six (50%) patients became anti-MDA5 antibody negative after therapy. After a mean follow-up of 31 months, RP-ILD relapse was observed in four (33%) patients in both the anti-MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti-MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti-MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti-MDA5 antibody exhibited symptoms of relapse during follow-up. Therefore, reincrease in anti-MDA5 antibody levels was associated with relapse. CONCLUSIONS: The anti-MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP-ILD relapse in patients with CADM or DM.

A retrospective analysis of nonresponse to daily teriparatide treatment.

UNLABELLED: Some patients with osteoporosis do not respond to teriparatide treatment. Prior bisphosphonate use, lower bone turnover marker (BTMs) concentrations, and lower early increases in BTMs were significantly associated with a blunted lumbar spine (LS) bone mineral density (BMD) response to daily treatment with teriparatide, although the impact was limited. INTRODUCTION: Some osteoporosis patients do not respond to teriparatide treatment. To better understand the factors underlying treatment nonresponses, we compared nonresponders' and responders' characteristics. METHODS: We retrospectively analyzed 354 male and female patients with osteoporosis who were administered teriparatide (20 µg/day) for 24 months. The patients were categorized as responders (≥3 % lumber spine (LS) bone mineral density (BMD) increase) or nonresponders (<3 % LS BMD increase), and the groups were compared. RESULTS: The univariate analyses determined that prior bisphosphonate use, a lower baseline procollagen type I N-terminal propeptide (PINP) concentration and a lower urinary N-telopeptide of type I collagen (uNTX) concentration at baseline were significantly associated with teriparatide nonresponses, but these factors were not significant following multivariate analysis. Diminished early increases in the bone turnover markers (BTMs) were also related to nonresponses after teriparatide treatment began. In the nonresponders, the mean (standard deviation (SD)) absolute LS and femoral neck (FN) BMD changes were -0.002 g/cm(2) (0.032) and -0.010 g/cm(2) (0.045), respectively. In the responders, the mean (SD) absolute LS and FN BMD changes were 0.118 g/cm(2) (0.056) and 0.021 g/cm(2) (0.046), respectively. The serum PINP and uNTX levels increased rapidly in both groups, but the responders showed higher early absolute serum PINP and uNTX increases. CONCLUSIONS: The factors associated with nonresponses were prior bisphosphonate use, lower baseline BTM levels, and lower early increases in the BTMs after starting teriparatide treatment, but the impact of these factors on achieving a ≥3 % LS BMD increase at 24 months was limited.

Usefulness of daily teriparatide treatment in elderly patients over 80 years of age.

UNLABELLED: The percent and absolute lumbar spine and femoral neck bone mineral densities and procollagen type I N-terminal propeptide (PINP) and urinary N-telopeptide level increases noted after teriparatide 20 µg/day treatment for 24 months were similar in the older (age ≥ 80 years) and younger (age < 80 years) subgroups. INTRODUCTION: Many individuals are living into their eighth and ninth decades, but little is known about the efficacy of osteoporosis medication for this population. We retrospectively compared usefulness of daily teriparatide therapy in osteoporosis patients ≥80 and <80 years to detect possible age-related differences. METHODS: We analyzed 628 osteoporosis patients treated with teriparatide 20 µg/day for 24 months. The primary efficacy measures were changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) over 24 months. Changes in serum procollagen type I N-terminal propeptide levels and urinary N-telopeptide (uNTX) excretion were also measured. Patients were divided into age subgroups (older, ≥80 years; younger, <80 years) for BMD and bone turnover marker comparison. RESULTS: In the older subgroup, the percent LS BMD significantly increased by 14.6 ± 10.4 % (mean ± SD) and FN BMD significantly increased by 4.5 ± 10.7 % at 24 months. In the younger subgroup, the percent LS BMD significantly increased by 12.2 ± 8.5 % and FN BMD significantly increased by 2.9 ± 8.3 % at 24 months. In the older subgroup, the mean absolute LS BMD change was 0.111 ± 0.071 g/cm(2) and FN BMD change was 0.019 ± 0.043 g/cm(2). In the younger subgroup, the mean absolute LS BMD change was 0.098 ± 0.065 g/cm(2) and FN BMD change was 0.016 ± 0.045 g/cm(2). The percent and absolute BMD increases in LS and FN and changes in PINP and uNTX were similar between the subgroups. CONCLUSIONS: The usefulness of daily teriparatide treatment is not age dependent.

Neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9orf72 is linked to TDP-43 pathology and not associated with aggregated forms of dipeptide repeat proteins.

AIMS: A hexanucleotide expansion in C9orf72 is the major genetic cause of inherited behavioural variant Frontotemporal dementia (bvFTD) and motor neurone disease (MND), although the pathological mechanism(s) underlying disease remains uncertain. METHODS: Using antibodies to poly-GA, poly-GP, poly-GR, poly-AP and poly-PR proteins, we examined sections of cerebral cortex, hippocampus, thalamus, cerebellum and spinal cord, from 20 patients with bvFTD and/or MND bearing an expansion in C9orf72 for aggregated deposits of dipeptide repeat proteins (DPR). RESULTS: Antibodies to poly-GA, poly-GP and poly-GR detected numerous rounded cytoplasmic inclusions (NCI) within granule cells of hippocampal dentate gyrus and those of the cerebellum, as well as 'star-burst' shaped NCI in pyramidal neurones of CA3/4 region of hippocampus. NCI were uncommon in Purkinje cells, and only very rarely seen in anterior horn cells. Poly-PA antibody detected occasional NCI within CA3/4 neurones alone, whereas poly-PR antibody did not identify any NCI but immunostained the nucleus of anterior horn cells, CA3/4 neurones and Purkinje cells, in patients with or without expansion in C9orf72, as well as in normal controls. Poly-GA antibody generally detected more DPR than poly-GP, which in turn was greater than poly-GR. All patients with bvFTD + MND or MND showed plentiful p62/TDP-43 positive inclusions in remaining anterior horn cells. CONCLUSION: Degeneration and loss of anterior horn cells associated with expansions in C9orf72 occurs in the absence of DPR, and implies that changes involving loss of nuclear staining for and a cytoplasmic aggregation of TDP-43 are more likely to be the cause of this.

MUC1-C activates the TAK1 inflammatory pathway in colon cancer.

The mucin 1 (MUC1) oncoprotein has been linked to the inflammatory response by promoting cytokine-mediated activation of the NF-κB pathway. The TGF-ß-activated kinase 1 (TAK1) is an essential effector of proinflammatory NF-κB signaling that also regulates cancer cell survival. The present studies demonstrate that the MUC1-C transmembrane subunit induces TAK1 expression in colon cancer cells. MUC1 also induces TAK1 in a MUC1(+/-)/IL-10(-/-) mouse model of colitis and colon tumorigenesis. We show that MUC1-C promotes NF-κB-mediated activation of TAK1 transcription and, in a positive regulatory loop, MUC1-C contributes to TAK1-induced NF-κB signaling. In this way, MUC1-C binds directly to TAK1 and confers the association of TAK1 with TRAF6, which is necessary for TAK1-mediated activation of NF-κB. Targeting MUC1-C thus suppresses the TAK1NF-κB pathway, downregulates BCL-XL and in turn sensitizes colon cancer cells to MEK inhibition. Analysis of colon cancer databases further indicates that MUC1, TAK1 and TRAF6 are upregulated in tumors associated with decreased survival and that MUC1-C-induced gene expression patterns predict poor outcomes in patients. These results support a model in which MUC1-C-induced TAK1NF-κB signaling contributes to intestinal inflammation and colon cancer progression.

Analysis of daily teriparatide treatment for osteoporosis in men.

UNLABELLED: The percent and absolute lumbar spine and femoral neck bone mineral densities and absolute procollagen type I N-terminal propeptide (PINP) increases following a 20-µg/day teriparatide treatment for 12 months were similar in men and women regardless of sex differences. INTRODUCTION: Several placebo-controlled studies have measured the effects of daily teriparatide in men and postmenopausal women with osteoporosis but none have directly compared the effects between these groups. We retrospectively compared the effects of daily teriparatide therapy in men and postmenopausal women with osteoporosis and investigated biochemical markers of bone turnover to detect possible sex differences. METHODS: Patients (563; 75 men and 488 women) with osteoporosis were retrospectively investigated. All patients were administered with teriparatide at 20 µg/day for 12 months. The primary efficacy measure was changed in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) after 12 months of treatment. The change in serum levels of procollagen type I N-terminal propeptide (PINP) and urinary N-telopeptide (uNTX) excretion after 4, 8 and 12 months of treatment were also measured. RESULTS: In men, the percent LS BMD significantly increased by 11.3 ± 9.9 % (mean ± standard deviation (SD)) and the FN BMD increased by 0.4 ± 6.4 % without a significant difference at 12 months. In postmenopausal women, the percent LS BMD significantly increased by 9.6 ± 8.1 % and the FN BMD significantly increased by 2.4 ± 7.8 % at 12 months. The percent and absolute BMD increases in LS and FN between men and women were similar. The absolute increases in PINP were similar in both groups at 4, 8 and 12 months. However, the absolute increases in uNTX were significantly lower in men than in women at 8 and 12 months. CONCLUSION: Daily teriparatide treatment was as effective in men as in postmenopausal women regardless of sex differences.

Three-dimensional computed tomographic volumetric changes in pancreas before and after living donor surgery for pancreas transplantation: effect of volume on glucose metabolism.

In the present study, we aimed to compare the pancreas volumetric changes before and after living donor surgery for pancreas transplantation, using three-dimensional (3D) computed tomography (CT) and glucose metabolism. Pancreatic volume (PV) measurement using 3D CT was performed in 13 consecutive donors who underwent distal pancreatectomy for simultaneous living donor pancreas and kidney transplantation. PV was measured using a workstation before and 3 months after living donor operation. As the parameters of glucose metabolism, hemoglobin A1c (HbA1c) level, fasting plasma glucose (FPG) level, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and insulinogenic index (IGI) were examined simultaneously with the PV measurement. The preoperative and postoperative PVs of pancreas was 30 ± 5 mL and 42 ± 9 mL, respectively. The postoperative PV was significantly higher than the preoperative PV (P < .01) and increased by approximately 40% at 3 months after surgery. The postoperative FPG and HbA1c levels were significantly higher than the preoperative values (P < .01). BMI decreased significantly after surgery (P < .01). No differences in HOMA-IR and IGI were noted between before and after surgery. Diabetes mellitus was not observed any of the 13 living donors during this period. Distal pancreatectomy for living donors caused an increase in the PV and maintained insulin resistance, but it was not sufficient to maintain glucose metabolism at the preoperative state.

Single-site retroperitoneoscopic donor nephrectomy.

We have performed retroperitoneoscopic nephrectomy for living kidney donor surgery since 2000. Recently, we introduced single-site retroperitoneoscopic donor nephrectomy (RDN) as a less invasive donor surgery. The procedure was performed in 7 donors (5 women and 2 men) by a single surgeon. The mean age and body mass index of the donors were 62.6 years (range, 53-74 years) and 24.3 kg/m(2) (range, 22.3-29.0 kg/m(2)), respectively. Left-sided nephrectomy was performed in all the donors. The donors were positioned in the right lateral position, and a 7-cm-long incision was made in the left flank. The incision was extended to the retroperitoneal space using the muscle-splitting technique. The retroperitoneal space was then expanded using an inflation balloon. A GelPOINT Advanced Access Platform (Applied Medical, Rancho Santa Margarita, Calif, United States) was placed in the incision. The subsequent technique and equipment were the same as those used in conventional 3-port RDN. The renal artery and vein were dissected using a vascular stapler, and the kidney graft was directly extracted through the incision. The mean operative time was 197 ± 28 minutes, warm ischemic time was 4.1 ± 1.2 minutes, and blood loss was 75 ± 113 mL. No statistical differences were found between the present method and conventional 3-port RDN. Intraoperative and postoperative complications were not observed in any of the donors. Graft function after transplantation was good, and delayed graft function was not observed in any of the recipients. This technique can be easily introduced in the clinical setting by surgeons experienced in RDN.

Study of transforming growth factor-ß1 gene, mRNA, and protein in Japanese renal transplant recipients.

BACKGROUND: Transforming growth factor (TGF)-ß1 may contribute to chronic allograft nephropathy and graft loss; however, the exact molecular mechanism remains unclear. Therefore, we assess the relationship between TGF-ß1 gene polymorphisms, expression, and development of allograft nephropathy. METHODS: We studied 135 renal transplant recipients at our hospital. TGF-ß1 gene polymorphisms (codons 10 and 25) were determined from peripheral blood leukocyte DNA. Plasma TGF-ß1 mRNA was measured by real-time polymerase chain reaction and TGF-ß1 protein levels were assessed by enzyme-linked immunosorbent assay. The relationship between TGF-ß1 genotyping, expression, and rejection and results of renal biopsy were evaluated. RESULTS: The genotype frequency of transplant recipients was 49.6%, 30.4%, and 20.0% for C/T, C/C and T/T at codon 10, 100% for G/G at codon 25, respectively. According to the criteria of Banff '97 classification, 24 cases were classified as acute rejection and whose genotypes were 16, 3, and 5 cases for C/T, C/C and T/T at codon 10. Plasma mRNA expression was elevated in 14 cases and decreased in 8 cases after acute rejection. We measured 267 specimens of TGF-ß1 protein and there was no relation between amount of TGF-ß1 protein and mRNA. CONCLUSION: Our results suggest that the relationship between plasma TGF-ß1 expression and the development of allograft nephropathy remains uncertain. Frequency of allograft rejection differ with TGF-ß1 codon 10 genotypes and the high-risk genotype was different from the reports of other countries.

Association of DNA amplification with progress of BK polyomavirus infection and nephropathy in renal transplant recipients.

PURPOSE: BK polyomavirus-associated nephropathy (BKVAN) is an important cause of renal allograft loss. Immunosuppression therapy in renal transplant recipients can lead to the reactivation of latent BK polyomavirus (BKV) infection, leading to BK viruria and viremia. This single-center study aimed to clarify the association between quantitative measurement of BKV DNA and the progression of BKV infection, and secondly to identify the risk factors associated with the evolution of viruria to viremia. METHODS: We retrospectively analyzed 266 patients who underwent renal transplantation in our center from October 2006 to February 2013. We examined the viral loads of BKV in urine and plasma by quantitative real-time polymerase chain reaction assay after screening all of the recipients by urinary sediment examination. BKVAN was diagnosed by histological examination with immunohistochemistry of the large T antigen in biopsy specimens. RESULTS: Overall, 22 recipients showed BK viruria alone, whereas 22 progressed to BK viremia, of which 6 patients were diagnosed with BKVAN. Among BKVAN patients, 2 cases progressed to graft loss at 59 months and 31 months after diagnosis, respectively. In BKVAN group, the plasma viral loads were significantly higher than those in viremia without nephropathy (P < .001). Multivariate analysis revealed that the evolution of viruria to viremia was associated with recipient age over 55 years (odds ratio, 32.08; 95% confidence interval, 2.1-489.5) and tacrolimus exposure (odds ratio, 11.98; 95% confidence interval, 1.34-107.04). CONCLUSIONS: The progression from viremia to BKVAN was strongly associated with increasing plasma viral loads for BKV DNA. The cutoff value of 1 × 10(4) copies/mL for plasma viral loads could differentiate between BKVAN and viremia alone. Further, recipient age over 55 years and tacrolimus exposure were independently associated with the evolution of viruria to viremia.

Pathologic findings of renal biopsy were a helpful diagnostic clue of stenosis of the iliac segment proximal to the transplant renal artery: a case report.

Common iliac artery stenosis after renal transplantation is a rare complication; it can occur in the course of hypertension and renal dysfunction. We report a case of suspected renal allograft rejection with iliac artery stenosis proximal to a transplanted kidney. A 52-year-old man with a history of cadaveric kidney transplantation 26 years previously underwent a second cadaveric kidney transplantation in the left iliac fossa because of graft failure 3 years before. In June 2012, the patient had progressive renal dysfunction. In July, a percutaneous needle biopsy was taken, and it showed no rejection; however, his renal function continued to get worse through September. A percutaneous allograft renal biopsy was performed under ultrasound guidance and showed hyperplasia of the juxtaglomerular apparatus and renin granules. Magnetic resonance angiography was used to evaluate the arteries in the pelvis and showed left common iliac artery stenosis, and a stent was placed. After percutaneous intervention, the patient's ankle brachial pressure index was within the normal range and the allograft function had improved.

Production of functional coagulation factor VIII from iPSCs using a lentiviral vector.

The use of induced pluripotent stem cells (iPSCs) as an autologous cell source has shed new light on cell replacement therapy with respect to the treatment of numerous hereditary disorders. We focused on the use of iPSCs for cell-based therapy of haemophilia. We generated iPSCs from mesenchymal stem cells that had been isolated from C57BL/6 mice. The mouse iPSCs were generated through the induction of four transcription factor genes Oct3/4, Klf-4, Sox-2 and c-Myc. The derived iPSCs released functional coagulation factor VIII (FVIII) following transduction with a simian immunodeficiency virus vector. The subcutaneous transplantation of iPSCs expressing FVIII into nude mice resulted in teratoma formation, and significantly increased plasma levels of FVIII. The plasma concentration of FVIII was at levels appropriate for human therapy at 2-4 weeks post transplantation. Our data suggest that iPSCs could be an attractive and prospective autologous cell source for the production of coagulation factor, and that engineered iPSCs expressing coagulation factor might provide a cell-based therapeutic strategy appropriate for haemophilia.

Deep-vein thrombosis after resection of musculoskeletal tumours of the lower limb.

The aim of this study was to define the incidence of venous thromboembolism (VTE) and risk factors for the development of deep-vein thrombosis (DVT) after the resection of a musculoskeletal tumour. A total of 94 patients who underwent resection of a musculoskeletal tumour between January 2003 and December 2005 were prospectively studied. There were 42 men and 52 women with a mean age of 54.4 years (18 to 86). All patients wore intermittent pneumatic compression devices and graduated compression stockings. Ultrasound examination of the lower limbs was conducted to screen for DVT between the fifth and ninth post-operative days. DVT was detected in 21 patients (22%). Of these, two were symptomatic (2%). One patient (1%) had a fatal pulmonary embolism. Patients aged ≥ 70 years had an increased risk of DVT (p = 0.004). The overall incidence of DVT (both symptomatic and asymptomatic) after resection of a musculoskeletal tumour with mechanical prophylaxis was high. It seems that both mechanical and anticoagulant prophylaxis is needed to prevent VTE in patients who have undergone the resection of a musculoskeletal tumour.

c-Fos induction in the brainstem following electrical stimulation of the trigeminal ganglion of chronically mandibular nerve-transected rats.

Neuronal excitability in the trigeminal sensory nuclei (TSN) changes after nerve transection. We examined the effects of chronic transection of the trigeminal nerve on the c-Fos-immunoreactivity in the TSN induced 2 h after 10 min of electrical stimulation of the trigeminal ganglion (TG) at C-fiber activating condition (1.0 mA, 5 ms, 5 Hz) in urethane-anesthetized rats. In the non-transected control rats, stimulation of the TG induced c-Fos-immunoreactive cells (c-Fos-IR cells) mostly in superficial layers (VcI/II) of the nucleus caudalis (Vc) in its full extent along the dorsomedial-ventrolateral axis, but modestly in the rostral TSN above the obex, the principal, oral, and interpolar nuclei. Three days, 1, 2, or 3 weeks after transection of the inferior alveolar (IAN), infraorbital, or masseteric nerves, the stimulation of the TG induced c-Fos-IR cells in the central terminal fields of the transected nerve in the rostral TSN and magnocellular zone of the Vc. However, the number of c-Fos-IR cells in the VcI/II decreased inside the central terminal fields of the transected nerve and increased outside the fields. These results indicate that transection of the trigeminal nerve increases the excitability of TSN neurons that receive inputs from injured mechanoreceptors and uninjured nociceptors, but decreases it from injured nociceptors. The altered c-Fos responses may imply mechanisms of neuropathic pain seen after nerve injury.

Altered expression of dermokine in skin disorders.

BACKGROUND: Although dermokine-ß, a glycoprotein expressed in epithelial cells, does not have significant homology to other proteins, its carboxyl-terminal domain shares a high pI value with many cytokines, suggesting similar functions. OBJECTIVE: To better understand the biology of dermokine, we here determined its localization under pathological conditions and examined factors that regulate its expression. METHODS: We generated an anti-human dermokine-ß/γ monoclonal antibody cross-reacting with the mouse protein. Using this antibody, immunohistological staining and Western blotting of dermokine-ß/γ were performed with various tissue samples. RESULTS: Although human dermokine-ß/γ was expressed in almost all granular layers, upper spinous layers of the skin were also stained with anti-dermokine-ß/γ antibody in inflammatory skin disorders. Dermokine-ß/γ was expressed in keratoacanthoma and a part of well-differentiated squamous cell carcinoma (SCC). However, dermokine-ß/γ was not detected in poorly differentiated SCC or tumours derived from non-keratinocytes. In mice, dermokine-ß/γ-expressed keratinocytes were increased in models of contact hypersensitivity, ultraviolet-irradiated skin injury and wound healing. Consistent with expanded distribution in inflammatory skin diseases, proinflammatory cytokines such as interleukin-1ß, interleukin-12, and tumour necrosis factor-α augmented dermokine-ß/γ expression in cultured human keratinocytes. In contrast, growth factors including epidermal growth factor, insulin-like growth factor-I, keratinocyte growth factor and transforming growth factor-α significantly reduced dermokine expression. CONCLUSION: These results provide novel insights into the physiological and pathological significance of dermokine in the epidermis.

Pesquisa de anticorpos contra maedi visna em ovinos nas microregiões de Botucatu, Campinas, Piedade e São Paulo, Estado de São Paulo / Survey for antibodies against maedi-visna virus in sheep in the regions of Botucatu, Campinas, São Paulo and Piedade, State of São Paulo, Brazil

O objetivo deste estudo foi avaliar a ocorrência da infecção pelo vírus Maedi-Visna em ovinos criados nas microrregiões de Botucatu, Campinas, Piedade e São Paulo do Estado de São Paulo. As amostras de soro sanguíneo foram colhidas de 226 ovinos e foi realizada a técnica de imunodifusão em gel de ágar para a detecção de anticorpos antivírus Maedi-Visna e verificou-se que nenhuma das amostras testadas foi sororeagente. Dessa forma, faz-se necessário um estudo mais amplo no estado, a fim de se confirmar a baixa ocorrência e importância da enfermidade no estado.

Survey for antibodies against maedi-visna virus in sheep in the regions of Botucatu, Campinas, São Paulo and Piedade, state of São Paulo, Brazil. The purpose of the study was to evaluate the occurrence of infection with maedi-visna virus in sheep raised in the regions of Botucatu, Campinas, Piedade and São Paulo, state of São Paulo, Brazil, that showed symptoms of the disease. Blood serum samples collected from 226 sheep were submitted to the agar gel immunodiffusion technique for detection of antibodies against maedi-visna virus, and none of the samples tested was serum reactive. In conclusion, the maedi-visna virus has low frequency in animals raised in the regions studied.