The mortality risk was equal in the two groups by day 106 of follow-up, and improved in the transplanted group thereafter. McDonald and Russ have reported similar findings using ANZDATA.14 An analysis of the period 1991–2000 found an 80% lower long-term risk of mortality between those transplanted and those remaining on the waiting list. Cameron et al. have performed a meta-analysis examining

the effect of transplantation on overall quality of life.15 Successful kidney transplantation was associated with improved BMS-777607 general wellbeing and less distress, when compared with continued haemodialysis or peritoneal dialysis. There are several individual studies that have examined quality of life issues in more detail. Evans et al. reported that 79.1% of transplant recipients describe near normal physical function, compared with only 50% of dialysis patients.16 Mental function scores were also higher in transplant recipients. Studies by both Gorlen et al.17 and Laupacis et al.18 found that the quality of life improvements associated with transplantation were sustained long term. However, transplantation continued to affect quality of life relative to normal.18 This was attributed to the side effects of immunosuppression,

comorbid conditions and the stress associated with the possibility of losing graft function. A detailed analysis of the relative costs of SB-3CT dialysis and PLX4032 in vitro transplantation has been performed by Kidney Health Australia.19 Estimates of the cost of home or satellite-based dialysis (haemodialysis and peritoneal) for an individual are approximately $45 000–$60 000 per year. Hospital-based haemodialysis is estimated to cost approximately $83 000 per year. Although the initial cost of transplanting an individual is estimated to be relatively high ($62 000 for the first year) the cost falls significantly thereafter (approximately $11 000 per year for year 2 and onwards). The estimated costs associated

with an individual live donor transplant are similar to those for an individual deceased donor transplant.19 A Canadian report estimated that transplanting an individual would result in savings of CAN$104 000 over a 20-year period.20 Only a brief account of the overall safety data will be summarized here. A much more detailed analysis of the literature regarding donor safety will follow in subsequent sections of these Living Kidney Donor guidelines. By and large, live kidney donation is considered to be safe for the majority of healthy donors. This contention, however, is based predominantly on large retrospective studies, which demonstrate that unilateral nephrectomy in healthy subjects is generally associated with a very low level of long-term risk.21–27 A meta-analysis published by Garg et al. has examined the development of proteinuria in donors.

Most cytokines were detected at very low levels before and after high-dose chemotherapy, and although changes were statistically significant, the biological relevance remains unclear. The BioRad research department uses a set of cytokine values they consider as ‘normal’. However, these values have not been

validated. Only our IL-5, IL-6 and INFγ results have values higher than the ‘normal’ BioRad values (Professor Tor Lea, University of Life Science, Norway, personal communication), which suggests that only these three cytokines reflect clinical significant differences. The complement system was slightly activated in this population PF-02341066 clinical trial of neutropenic lymphoma patients as revealed by a significant increase in both C3bc, an early marker of activation, and TCC, a late marker of activation. The complement activation we found histone deacetylase activity might contribute to a low-grade, probably sterile, inflammatory response. Activation is far greater in some patients with non-neutropenic severe bacterial infection [21]. Constitutively low MBL levels have been associated with a more severe course of febrile neutropenia [8–13, 22]. In contrast to this, we did not find that low MBL values affected the clinical course in our patients. However,

our patients with decreased MBL levels did not develop bacteriaemia. Collectively, our data do not support any role for MBL in febrile neutropenia in a patient population with modest clinical symptoms. The tobramycin once-daily group

had peak tobramycin concentrations generally three times higher than those who received tobramycin three times daily, even though the total tobramycin doses were the same. Comparing the immune responses in patients receiving tobramycin once versus three times daily (Table 3), we found significantly higher increases in several of the proinflammatory cytokines in the patients receiving tobramycin once daily. This has not previously been described [17, 23]. Tobramycin has been associated with increased release from polymorphonuclear leucocytes (PMN) of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα, but not during the anti-inflammatory IL-10 [22]. The highest levels have been observed for IL-6 [23]. We found increases in IL-1b, IL-4, IL-6, IL-7, IL-8, G-CSF, GM-CSF, INFγ and TNFα (Table 2), results that are in accordance with the previous findings [23]. However, these previous findings have not been associated with different tobramycin concentrations. Our patients were neutropenic, abating a possible PMN-mediated response to tobramycin, but our data still indicate that the higher peak concentrations following once-daily dosing have caused a stronger proinflammatory response. This most likely reflects production of these cytokines by other immune cells, such as T-lymphocytes.

[3, 4] IPA accounts for 90–98% of invasive Aspergillus infections; however, extrapulmonary aspergillosis may be present in 25–60% of cases and is almost always caused by haematogenous spread of pulmonary foci. IA has a wide spectrum of clinical presentations, making diagnosis challenging. In 2006, it has been reported that only a quarter of IA cases confirmed

by autopsy had been diagnosed premortem, which demonstrates that there is a lot to be done in terms of early diagnosis.[5, 6] Lewis and colleagues published an autopsy-based study in 2013 which showed that rates of premortem diagnosis of Aspergillus infections might have improved over the last decade. They analysed autopsy data from over 20 years and found that in the first 5 years of the study 84% of the invasive

fungal buy GW-572016 infections were diagnosed postmortem, while in the last 4 years this number decreased to 49%.[7] Most likely reasons for an ongoing increase of IA diagnosed premortem are the introduction of new diagnostic tools, such as Galactomannan or Lateral flow Device testing as well as improved culture methods.[3, 8-10] IA is still associated with mortality rates of about 40%. Early initiation of systemic antimould therapy remains the most important measure Acalabrutinib cell line to reduce mortality.[11] Surgical debridement is an important therapeutic option mainly in cases of extrapulmonary IA. Evidence for surgical interventions exists primarily in localised infections of children and adults. In disseminated infections, the evidence for the benefit of surgical interventions other than for diagnostic purposes is poor. The main intentions for surgical interventions are: (i) to obtain material for diagnosis, (ii) to decrease the burden of infected tissue and (iii) to facilitate antifungal penetration. Surgical/invasive interventions are nearly always indicated only in combination with systemic

antifungal therapy. Naturally, there are no randomised or controlled clinical studies available on surgical interventions in IA, limiting the evidence ADP ribosylation factor to mostly uncontrolled single-centre case series (Table 1).[12] Here, we will review the role of surgical interventions in the treatment of different clinical manifestations of IA. Cerebral (intradural) aspergillosis is associated with the highest mortality of all different manifestations of IA. The infection spreads to the CNS either by haematological dissemination from pulmonary foci or expands directly from paranasal sinus infection. Aspergillus spp. may also enter the CNS due to traumatic inoculation or during surgical procedures.[13] CNS aspergillosis often presents with neurological symptoms, such as altered mental status, a focal neurological deficit, seizure, persistent headache or rarely meningeal signs.

5A), suggesting that the glycan-dependent antibodies in Serum 45 have distinct epitope specificity from that of PG9. The neutralization activity of Serum 15 against CNE6 was markedly reduced by kifunensine treatment of the virus, in contrast to JRFLkifu that became slightly more sensitive than the wild-type JRFL to Serum 15 (Fig. 5B), suggesting that both PG9-like and 2G12-like antibodies existed in Serum 15 and PG9-like antibody only mediates part of its neutralizing activity against CNE6 and 2G12-like antibody may contribute a major neutralizing activity against Venetoclax cost JRFL. Serum 13 and CNIgG29 neutralized CNE6kifu

and JRFLkifu more efficiently than CNE6 and JRFL (Fig. 5C, D), indicating that the neutralizing activities of Serum 13 and CNIgG29 to CNE6 and JRFL Selleck MLN0128 were probably mediated by 2G12-like antibody. Serum 45 samples (45-1, 45-2, 45-3), collected from one donor at different time points spanning nearly 23 months with S45-1 the earliest sample and S45-3 the latest (Table 3), were investigated for their reactivities against gp120s and peptides. Results showed that all of these three sequential serum samples could react with various gp120s (Fig. 6A) and had similar antibody titres against gp120AE (Fig. 6B). MPER-directed antibodies did

not exist in all three sera (Figure S3). Additionally, the neutralizing activities of these three serum samples against CNE6, CNE55, CNE6kifu, CNE55kifu, CNE6N160K and CNE55N160K

were very similar (Fig. 6C). In order to further understand the nature of the glycan-dependent antibodies in Serum 45 that differ from PG9, we further investigated the antibody specificities through depletion study. After being depleted by gp120AE-coupled beads, Serum 45 completely lost binding reactivities to both gp120IIIB and gp120AE, Farnesyltransferase but still retained weak reactivity to V1V2BAL recombinant protein. In contrast, V1V2BAL recombinant protein-coupled beads-depleted Serum 45 showed almost no reduction in its binding reactivity with gp120IIIB and gp120AE although V1V2BAL-specific reactivity was removed completely (Fig. 7A). BSA-coupled beads had no effect on the serum binding reactivity with gp120IIIB, gp120AE and V1V2BAL (Fig. 7A), suggesting that the antibody depletion was antigen specific. To confirm that the desired antibodies were depleted completely, the reactivities of serial dilutions of the depleted Serum 45 to various respective antigens were tested by ELISA (Fig. 7B). The neutralization activity of the depleted Serum 45 was also determined (Fig. 7C,D). Results showed that the neutralizing activities of gp120AE-depleted Serum 45 against CNE6 and CNE55 were both significantly reduced. In contrast, the neutralization activities of V1V2BAL recombinant protein-depleted Serum 45 were not significantly affected.

Additionally, in the primate complexes, sequences highly homologous to five exons of CLEC-2 were found in the genomic region directly upstream of the CLEC9A gene (CLEC-2 exon 2: 96%, CLEC-2 exon 3: 91%, CLEC-2 exon 4: 90%, CLEC-2 exon 5: 87% and CLEC-2 exon 6: 88%). This suggests that a duplication of exons 2–6 of the CLEC-2 gene followed by an inversion of the region containing the complete CLEC-2 and CLEC12B genes has taken place in a common primate ancestor (Fig. 1B). Interestingly, sequences highly homologous to parts of the CLEC2 gene were also found in the 5′-UTR of CLEC9A mRNA, indicating that GPCR & G Protein inhibitor upstream untranslated exons 1 and 3 of CLEC9A are derived from intronic

regions, while exon 2 is derived from the second CTLD exon of an ancestral CLEC2 gene. These three exons upstream of the coding region of CLEC9A form a 5′-UTR of about 640 bp which contains an open reading frame (ORF) selleck chemical of 273bp starting at position −362 and ending at position −87 relative to the CLEC9A translation initiation

site. Because mini ORF in the untranslated region of several genes have been shown to interfere with the translation of the corresponding proteins [34–36], it is of interest to note that the existence of an internal ribosomal entry site (IRES) is predicted directly 5′ of the start codon (position −93 to −1), which could mediate 5`-end-independent ribosomal attachment to an internal position in the mRNA and could thereby facilitate CLEC9A translation. Based on the analysis of their protein sequences, the genes of the NK gene complex can be classified into two distinct subgroups. The first group of genes indeed encodes lectin-like receptors that show the typical lectin structure consisting of six exons coding for a N-terminal cytoplasmic region, a transmembrane

region, a neck region and three C-type lectin-like domains [37]. The second group consists only of the two proteins, FLJ31166 and GABARAPL1, and both do not code for lectin-like receptor proteins. Homologies were detected only for transmembrane regions of human and murine FLJ31166, but not for other protein domains, nor was it possible to find homologies to other known 5FU proteins. The exon–intron structure of human und murine GABARAPL1 is made up of four coding exons, and the protein does not contain a transmembrane region. The first exon has been reported to encode a tubulin-binding site, whereas the sequences of exons three and four code for a GABA receptor-binding site [26]. Regarding their amino acid sequences, lectin-like receptors share common characteristics, such as six highly conserved cysteine residues in the extracellular part of the protein, and some also contain motifs involved in Ca2+- and ligand binding, namely EPN (mannose binding)/QPD (galactose binding) and WND [3, 37]. As shown in Fig. 2A, the human and murine homologues of the novel lectin-like proteins CLEC12B and CLEC9A show most of the typical features of lectin-like receptors.

brasiliensis, sets of mice from each study group were sacrificed buy ABT-263 at different times. After total RNA extraction from the NI-MG, ISSI-MG, CI-MG, and NbI-MG foot tissue samples, RT-PCR was performed to amplify fragments of the mRNA corresponding to the receptors, using the mRNA for β-actin as a control. All photographs were processed digitally to enhance their quality. In Fig. 1, the band intensities of the amplified fragments are shown. The intensity of the NI-MG band was considered to be the constitutive basal level for each receptor (T0). The intensity of the bands relative to that of β-actin was constant for all tested tissues at all different

times. The density of the band corresponding to the expression of TLR2 was more intense than that of the baseline band after 2 h. The maximum intensity was observed at 4 h, after which a slight decrease was observed; it then remained constant for the subsequent time points. The density of the band corresponding to the expression of

TLR4 remained similar to the baseline level after selleck 2 and 4 h, but after 8 h, it showed decreasing intensity for the rest of the study. Figure 2 shows the clinical features of three representative times in the evolution of experimental actinomycetoma. A few minutes after inoculation with N. brasiliensis, a slight subcutaneous swelling was observed in the right foot pad (Fig. 2a, arrow). At 20 days PI, a large area of induration with notable erythema

had developed (Fig. 2b). At 6 months PI, numerous abscesses were observed under the skin and some sinus tracts extended to the surface, resulting in a necrotic area (Fig. 2c, arrow). In Fig. 3, the analysis of the densitometry values obtained for the intensity of the TLR2 and TLR4 bands in the three mouse groups is shown. Figure 3a shows that a significant increase in TLR2 expression was observed in the NbI-MG with respect to the baseline value (33.87±5.92 ng) at all assessed times, with the peak of expression at 4 h PI (73.84±11.82 ng). In the ISSI-MG (Fig. 3b), TLR2 expression decreased Cell Penetrating Peptide significantly at 2 h PI and returned to the baseline level after 4 h. In the CI-MG (Fig. 3c), the expression of TLR2 decreased significantly at 2, 4, and 8 h PI relative to healthy individuals; at subsequent times, the values showed a tendency to increase towards the baseline level. TLR4 showed high constitutive expression (93.49±20.7 ng). In the NbI-MG (Fig. 3d), the expression of this receptor showed a gradual decrease PI, with the lowest value occurring at 50 days PI (20.59±18.3 ng). A significant difference from the baseline levels was found at all times after 8 h PI. In the ISSI-MG (Fig. 3e), a nonsignificant decrease was observed 2 h PI, after which the values showed a tendency to return to the baseline level. In the CI-MG (Fig. 3f), TLR4 expression showed a pattern similar to that of TLR2 expression.

To our knowledge, this is the first study to report association of these genotypes in household contacts. Based on MDR analysis, high-risk combination between IL-1β and IL-10 genes suggests that these SNPs interact synergistically affecting signalling impairment, and hence, effector mechanisms significantly leading to pathogenesis of tuberculosis. Our study illustrates that IL-1β CC and IL-10 GG genotypes may be useful for early detection of the disease

in high-risk learn more individuals, that is, household contacts. However, there is a need to evaluate the data in large sample size. We thank Bhagwan Mahavir Trust and staff of the free chest clinic Mahavir PPMDOTS, Tuberculosis Unit (TU). Financial support was provided by DBT-RGYI (Sanction no: 102/IFD/PR/2029/2007-2008 dated 18/01/2008) and COE (Sanction No: BT/01/COE/07/02, dated 30/12/08). “
“Approximately 2 billion people are infected with Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), and an estimated 1.5 million individuals die annually from TB. Presently, Mycobacterium bovis BCG remains the only licensed TB vaccine; however, previous studies suggest its protective efficacy wanes over time and fails in preventing pulmonary TB. Therefore, a safe and effective vaccine is urgently required to replace BCG or boost BCG immunizations. Our previous studies revealed

that mycobacterial proteins are released via exosomes from macrophages infected with M. tuberculosis Cyclic nucleotide phosphodiesterase or pulsed with M. tuberculosis HM781-36B culture filtrate proteins (CFP). In the present study, exosomes purified from macrophages treated with M. tuberculosis CFP were found to induce antigen-specific IFN-γ and IL-2-expressing CD4+ and CD8+ T cells. In exosome-vaccinated mice, there was a similar TH1 immune response but a more limited TH2 response compared to BCG-vaccinated mice.

Using a low-dose M. tuberculosis mouse aerosol infection model, exosomes from CFP-treated macrophages were found to both prime a protective immune response as well as boost prior BCG immunization. The protection was equal to or superior to BCG. In conclusion, our findings suggest that exosomes might serve as a novel cell-free vaccine against an M. tuberculosis infection. Currently, more than 2 billion individuals have been infected with Mycobacterium tuberculosis and about 5–10% those infected will develop active tuberculosis (TB) disease during their lifetime. In 2011, there was an estimated 8.7 million new cases of TB (13% co-infected with HIV) and among the approximate 1.5 million individuals who died from TB, 430 000 were HIV positive [1]. In 1921, the vaccine Mycobacterium bovis BCG, developed by Albert Calmette and Camille Guérin, was first used in humans [2, 3]. Currently, M. bovis BCG has been administrated to over 4 billion people and remains the only licensed anti-TB vaccine worldwide [4].

Berger in 1968.1 Histopathologically,

IgA nephropathy is characterized by expansion of the glomerular mesangial matrix with mesangial cell proliferation. Glomeruli typically contain generalized-diffuse granular mesangial Veliparib deposits of IgA (mainly IgA1), IgG and C3. Clinically, patients with IgA nephropathy showed microscopic and/or macroscopic haematuria and/or proteinuria. Advanced patients progress to renal hypertension and end-stage kidney disease (ESKD). Approximately 30–40% of patients with IgA nephropathy develop hypertension and progress to ESKD. Recognizing those patients likely to progress to ESKD and identifying suitable therapeutic targets are major goals for nephrologists. Central to achieving these goals is the development of suitable animal models to provide a detailed understanding of the underlying pathogenesis of IgA nephropathy. Because pathogenesis and radical treatment for IgA nephropathy are still not established, it is necessary to study them using animal models.2,3 Several investigators, including Rifai et al.4 and Emancipator et al.,5 reported experimental animal models for IgA nephropathy.

In 1985, Imai et al.6 first reported that the ddY strain of mouse can serve as a spontaneous animal model for human IgA nephropathy. These mice show mild proteinuria without haematuria and mesangioproliferative glomerulonephritis with severe glomerular find more IgA deposits in association with an increase in serum IgA level. Marked deposition of IgA and C3 in the glomerular mesangial areas in association with an increase in the levels of macromolecular IgA appears in sera of these mice with aging. Electron-dense deposits are observed in the

glomerular mesangial areas by electron microscopy. These findings appear at more than 40 weeks of age. It was found that ddY mice derived from non-inbred dd-stock selleck kinase inhibitor mice brought from Germany before 1920 and then raised in Japan developed spontaneously IgA-dominant deposition in the glomerular mesangium.6 Muso et al.7 reported that dimeric and polymeric IgA can be eluted from diseased glomeruli of aged ddY mice. However, the incidence of IgA nephropathy in ddY mice is highly variable. Miyawaki et al.8 succeeded in generating an IgA nephropathy mouse with a high incidence and early onset of glomerular IgA deposition. The selected ddY line (high serum IgA ddY (HIGA) mice) showed only mild proteinuria (100–300 mg/dL) without haematuria. It appears that immunological aberrations in ddY mice resemble those in human IgA nephropathy although these mice did not show microscopic haematuria and severe glomerular injuries. These findings from ddY mice appear to be useful in studying the pathogenesis and treatment for patients with IgA nephropathy.

We show that resident γδ

T cells are an early, innate-like source of IL-17 and that γδ T cells amplify Th17 responses and exacerbate colitis development. Moreover, we also demonstrate that Foxp3+ TREG cells also suppress the expansion and cytokine-producing potential of resident γδ T cells at an early stage of colitis development. These findings will increase our understanding of TREG cell-mediated control of bacterially driven mucosal inflammation and may enable us to design novel approaches to potentiate TREG-cell function and consequential tolerance induction in various chronic inflammatory disorders. WT, TCR-β−/− and RAG2−/− B6 CHIR-99021 purchase mice were obtained from Taconic Laboratories, while GFP transgenic B6 (pUbi-GFPtg) mice were provided by Dr. Schaefer 56. All mice were generally used at 6–10 wk of age. Mice were housed and bred under specific pathogen-free conditions according to institutional guidelines at McGill University (animal use protocol ♯4715). For in vivo adoptive transfer, CD4+CD25+

(TREG), CD4+CD25− (TEFF), CD4+ (total) and γδ TCR+ T-cell subsets from appropriate mice were purified from a pool of splenocytes and LN cells using the autoMACS cell sorter (Miltenyi Biotec) according to the manufacturer’s protocol. Briefly, CD4+CD25+ T-cell fraction (∼90% purity) was obtained by positive selection for CD25. The remaining cells were used to obtain CD4+CD25− TEFF fraction (>93% purity) by positive selection for CD4. CD4+ and γδ TCR+ T-cell subsets (>93 and > 90% purity, respectively) selleck chemicals were obtained by positive selection for CD4 or γδ TCR. For in vitro suppression assays, T-cell subsets were isolated using a FACSAria™ Cell

Sorter with a purity > 98%. CD4+CD25− TEFF or CD4+CD25+ TREG cells were sorted from WT B6. CD3+γδ TCR+ T cells were sorted form TCR-β−/− mice. MACS purified CD4+CD25− TEFF (1.3×106), a mixture of CD4+CD25+ TREG (0.2×106) and CD4+CD25− TEFF Cytidine deaminase (1.3×106) T cells, and (0.7×106) γδ T cells from GFP-Tg or WT donor mice were intravenously transferred into TCR-β−/− or RAG2−/− recipient mice. Individual body weight, as an indicator of disease incidence, was monitored and compared with body weight at the start point. Colonic tissues were collected from recipient mice and either directly mounted in optimum cutting temperature compound or fixed in 10% paraformaldehyde followed by paraffin embedding. Sections of 10 μm for frozen and 6 μm for paraffin embedded tissues were made, subjected to hematoxylin/eosin staining and analyzed by a pathologist giving the score from 0–4 based on previously described criteria 57, 58. In order to isolate lymphocytes from LP, a modified protocol from 59 was used. Briefly, colonic tissues from recipient mice were isolated, washed with PBS and cut into pieces.

UC manifests as a TH2 cytokine (IL-4, IL-5, and IL-13)-driven erosion of the intestinal epithelium 23, 24, 51–53. On the contrary, Crohn’s colitis is driven by TH1 and TH17 cytokines (IFN-γ, IL-17A/F) 3, 54. Although the etiology of UC remains unclear, recent studies

have focused on the role of IL-33, an IL-1 family cytokine that instructs type 2 inflammation 25. In human UC patients, IL-33 expression is highly upregulated within the intestinal mucosa and IL-33-deficient mice are protected from DSS-induced intestinal immunopathology 23, 24, 55. Our data show that CD68TGF-βDNRII mice produce high levels FK506 ic50 of IgE and IL-33 within the colon following DSS-induced gut injury. One source of IL-33 in CD68TGF-βDNRII mice was intestinal Mϕs, which demonstrates that TGF-β serves an important role in limiting intestinal inflammation through suppression of IL-33. This may be an important mechanism that could partially explain the reason how mutations in TGF-βRII

in humans are associated with increased risk for UC and UC-associated cancer 19, 20. Thus, it Depsipeptide cell line is tempting to speculate that blockade of IL-33 during UC may help to reduce the severity of colitis in these patients. Overall, we demonstrate that mice engineered to have a specific impairment of TGF-β responsiveness in Mϕs develop increased severity of DSS-induced colitis during the resolution phase. This suggests that TGF-β-mediated regulation of Mϕs function serves an important role in the suppression of intestinal inflammation following acute injury. In this regard, it will be important to determine whether CD68TGF-βDNRII mice develop altered susceptibility or resistance to infectious diseases or show defects in tissue repair mechanisms in other model

systems. The Non-specific serine/threonine protein kinase TGF-βDNRII construct was obtained from Dr. Chung Lee at Northwestern University in a plasmid that encodes the extracellular and transmembrane domains, but lacks the cytoplasmic region for human TGF-β receptor II (−5 to 553), which blocks TGF-β responsiveness in vivo 56. This region was subcloned into a modified pcDNA3.1™ (Invitrogen) using Not 1 and Xho 1. The 1 kb promoter sequence from human CD68 (macrosialin) including the 89 bp intronic enhancer (provided by Peter Murray at St. Jude Hospital) 26 was inserted 5′ to TGF-βDNRII as a BamH1-EcoRV fragment and confirmed by restriction digest and DNA sequencing. CD68TGF-βDNRII mice were generated by pronuclear injection of fertilized C57BL/6 oocytes at the University of Cincinnati Transgenic core facility. Offspring were analyzed for genotype by PCR using primers specific for CD68IVS1 and human TGF-β type II. All mice used in the study were age-matched male mice on a C57BL/6 background. All experiments were performed with age-/sex-matched nontransgenic littermates used as controls.