The Roles of Settings in Supporting Immigrants' Resistance to Injustice and Oppression: A Policy Position Statement by the Society for Community Research and Action: A Policy Statement by the Society for Community Research and Action: Division 27 of the American Psychological Association.

In 2018, in response to increasingly oppressive and widespread federal immigration enforcement actions in the United States (U.S.) and around the globe - including family separation, immigration raids, detention, deportation of people who have lived in the country for much of their lives - the Society for Community Research & Action produced a statement on the effects of deportation and forced separation on immigrants, their families, and communities (SCRA, 2018). The statement focused exclusively on the impacts of deportation and forced family separation, documenting the damage done by oppressive U.S. policies and practices. We felt it was imperative to document this harm, and yet were uncomfortable producing a narrow paper that focused solely on harm. There are multiple ways immigrants and their allies resist deportation and other forms of oppression. This resistance is done individually, collectively, and in settings that vary in size and scope, including community-based, faith-based, direct care, and educational settings, as well as entire municipalities and transnational organizing settings. Settings facilitate resistance in many ways, focusing on those who are oppressed, their oppressors, and systems of oppression. In this statement, we describe the unique and overlapping ways in which settings facilitate resistance. We situate this review of the scientific and practice literature in the frameworks of change through social settings, empowering settings, healing justice, and decolonization. We also document recommendations for continued resistance.

Accelerated storage test of betalains extracted from the peel of pitaya (Hylocereus cacti) fruit.

Betalains are nitrogen-containing colorants with antioxidant properties that can be found in plant materials such as pitaya peels. However, thermo-stability of these natural colors may vary with different source, yet few study has reported the rate orders of degradation for pitaya-sourced betalains. In this study, accelerated storage test of betalains, namely betacyanin and betaxanthin, extracted from pitaya peel are investigated by heat treatment of the extract at elevated temperatures. The results show that degradation kinetics of betacyanins and betaxanthins can both fit first-order kinetics and Arrhenius equation with activation energies at - 49.2 kJ/mol and - 40.0 kJ/mol, respectively. The result of Student's t-test indicated that the predicted k values are statistically the same as compared to their corresponding experimental values. LSD estimation also showed that k value variation tendency of the two betalains appears to be the same at 60 °C or below, while betacyanins tend to degrade faster above 80 °C than betaxanthins due to higher coefficient value of k value variation. This result also suggests that the pitaya-sourced betalains tend to degrade gradually even though they are stored under refrigerated condition. However, the betalains showed appreciably lower rate of degradation if they are processed at 60 °C or below.

The pharmacokinetics of oclacitinib maleate, a Janus kinase inhibitor, in the dog.

The pharmacokinetics of oclacitinib maleate was evaluated in four separate studies. The absolute bioavailability study used a crossover design with 10 dogs. The effect of food on bioavailability was investigated in a crossover study with 18 dogs. The breed effect on pharmacokinetics was assessed in a crossover study in beagles and mongrels dogs. Dose proportionality and multiple dose pharmacokinetics were evaluated in a parallel design study with eight dogs per group. In all four studies, serial blood samples for plasma were collected. Oclacitinib maleate was rapidly and well absorbed following oral administration, with a time to peak plasma concentration of <1 h and an absolute bioavailability of 89%. The prandial state of dogs did not significantly affect the rate or extent of absorption of oclacitinib maleate when dosed orally, as demonstrated by the lack of significant differences in pharmacokinetic parameters between the oral fasted and oral fed treatment groups. The pharmacokinetics of oclacitinib in laboratory populations of beagles and mixed breed dogs also appeared similar. Following oral administration, the exposure of oclacitinib maleate increased dose proportionally from 0.6 to 3.0 mg/kg. Additionally, across the pharmacokinetic studies, there were no apparent differences in oclacitinib pharmacokinetics attributable to sex.

Nationwide outbreak of Salmonella Montevideo infections associated with contaminated imported black and red pepper: warehouse membership cards provide critical clues to identify the source.

In November 2009, we initiated a multistate investigation of Salmonella Montevideo infections with pulsed-field gel electrophoresis pattern JIXX01.0011. We identified 272 cases in 44 states with illness onset dates ranging from 1 July 2009 to 14 April 2010. To help generate hypotheses, warehouse store membership card information was collected to identify products consumed by cases. These records identified 19 ill persons who purchased company A salami products before onset of illness. A case-control study was conducted. Ready-to-eat salami consumption was significantly associated with illness (matched odds ratio 8·5, 95% confidence interval 2·1-75·9). The outbreak strain was isolated from company A salami products from an environmental sample from one manufacturing plant, and sealed containers of black and red pepper at the facility. This outbreak illustrates the importance of using membership card information to assist in identifying suspect vehicles, the potential for spices to contaminate ready-to-eat products, and preventing raw ingredient contamination of these products.

Potential of probiotic strains to modulate the inflammatory responses of epithelial and immune cells in vitro.

Lactobacilli are important human commensal microbiota that are considered to be probiotic as they have been shown to reduce pathogenic infections and chronic inflammation. This study compared 4 strains of lactobacilli for their probiotic potential. These 4 strains showed varying capacities for adhesion and cytokine induction (interleukin [IL]-8 and IL-10) in different human epithelial cells, such as primary cultures of buccal cavity cells, and established cell lines derived from epithelia of the pharynx, intestine and cervix. After exposure to lactobacilli, secretion of cytokines (IL- 10, IL-12p70, interferon-?, and tumor necrosis factor-?) was induced at varying levels in different cultures of human immune cells, including dendritic cells, monocyte-depleted peripheral blood mononuclear cells, CD14+ cells, CD4+CD25- T cells, and regulatory T-cells. Growth inhibition of pathogenic strains was detectable in the presence of lactobacilli in vitro. Moreover, among the 4 strains tested, Lactobacillus salivarius sp. salicinius AP-32 was found to have the highest probiotic potential. This study highlights the complex host-pathogen-microbiota interactions and indicates that a combination of strains may have to be used to provide all the desirable probiotic benefits.

Superficial temporal artery injury and delayed post-cranioplasty infection.

OBJECTIVE: Complications after cranioplasty after decompressive craniectomy (DC) have been reported to be as high as 40%. The superficial temporal artery (STA) is at substantial risk for injury in standard reverse question-mark incisions that are typically used for unilateral DC. The authors hypothesize that STA injury during craniectomy predisposes patients to post-cranioplasty surgical site infection (SSI) and/or wound complication. METHODS: A retrospective study of all patients at a single institution who underwent cranioplasty after decompressive craniectomy and who underwent imaging of the head (computed tomography angiogram, magnetic resonance imaging with intravenous contrast, or diagnostic cerebral angiography) for any indication between the two procedures was undertaken. The degree of STA injury was classified and univariate statistics were used to compare groups. RESULTS: Fifty-four patients met inclusion criteria. Thirty-three patients (61%) had evidence of complete or partial STA injury on pre-cranioplasty imaging. Nine patients (16.7%) developed either an SSI or wound complication after cranioplasty and, among these, four (7.4%) experienced delayed (>2 weeks from cranioplasty) complications. Seven of 9 patients required surgical debridement and cranioplasty explant. There was a stepwise but non-significant increase in post-cranioplasty SSI (STA present: 10%, STA partial injury: 17%, STA complete injury: 24%, P=0.53) and delayed post-cranioplasty SSI (STA present: 0%, STA partial injury: 8%, STA complete injury: 14%, P=0.26). CONCLUSIONS: There is a notable but statistically non-significant trend toward increased rates of SSI in patients with complete or partial STA injury during craniectomy.

Eradication of Helicobacter pylori infection by the probiotic strains Lactobacillus johnsonii MH-68 and L. salivarius ssp. salicinius AP-32.

BACKGROUND: The current therapy for Helicobacter pylori infection includes antimicrobial agents and proton pump inhibitors. We have examined the ability of Lactobacillus spp. to inhibit H. pylori infection. MATERIALS AND METHODS: Probiotic strains isolated from samples of adult feces, infant feces, breast milk, and vaginal swab collected from healthy volunteers in Taiwan and commercially available strains were screened for antagonism toward H. pylori. Inhibition liquid culture assay was used to screen potential anti-H. pylori activity. Then, we performed agar plate inhibition assay, and assays to determine the capacity of probiotics for adhesion, and inhibition and killing of H. pylori, and measured the levels of IL-8 and IL-10. Using animal models, we studied regulation of gastric acid and histopathological changes accompanying anti-H. pylori activity. RESULTS: We found that six of the tested strains suppressed urease activity of H. pylori: Lactobacillus acidophilus TYCA08, L. acidophilus TYCA15, L. johnsonii MH-68, and L. salivarius subsp. salicinius AP-32 were more effective than the others. In vivo, L. johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 alone or in combination, reduced the H. pylori load in the gastric mucosa, and also reduced inflammatory chemokine expression and lymphocyte infiltration. CONCLUSIONS: Lactobacillus johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 effectively suppress H. pylori viability, and when used as probiotics, they may help decrease the occurrence of gastritis, and even reduce the risk of H. pylori infection.

The influence of initial spinal cord haematoma and cord compression on neurological grade improvement in acute traumatic spinal cord injury: A prospective observational study.

STUDY DESIGN: Prospective observational cohort study linked with administrative data. OBJECTIVES: Magnetic Resonance Imaging (MRI) is routinely performed after traumatic spinal cord injury (TSCI), facilitating early, accurate diagnosis to optimize clinical management. Prognosis from early MRI post-injury remains unclear, yet if available could guide early intervention. The aim of this study was to determine the association of spinal cord intramedullary haematoma and/or extent of cord compression evident on initial spine MRI with neurological grade change after TSCI. METHODS: Individuals with acute TSCI ≥16 years of age; MRI review. Neurological gradings (American Spinal Injury Association Impairment Scale (AIS)) were compared with initial MRI findings. Various MRI parameters were evaluated for prediction of neurological improvement pre-discharge. RESULTS: 120 subjects; 79% male, mean (SD) age 51.0 (17.7) years. Motor vehicle crashes (42.5%) and falls (40.0%) were the most common injury mechanisms. Intramedullary spinal cord haematoma was identified by MRI in 40.0% of patients and was associated with more severe neurologic injury (58.3% initially AIS A). Generalised linear regression showed higher maximum spinal cord compression (MSCC) was associated with lower likelihood of neurological improvement from initial assessment to follow up prior to rehabilitation discharge. Combined thoracic level injury, intramedullary haematoma, and MSCC > 25% resulted in almost 90% probability of pre-discharge AIS (grade A) remaining unchanged from admission assessment. CONCLUSIONS: MRI is a vital tool for evaluating the severity and extent of TSCI, assisting in appropriate management decision-making early in TSCI patient care. This study adds to the body of knowledge assisting clinicians in prognostication.

Comparative analysis of antibody responses to outer surface protein (Osp)A and OspC in dogs vaccinated with Lyme disease vaccines.

Lyme disease (LD), the most common tick-borne disease of canines and humans in N. America, is caused by the spirochete Borreliella burgdorferi. Subunit and bacterin vaccines are available for the prevention of LD in dogs. LD bacterin vaccines, which are comprised of cell lysates of two strains of B. burgdorferi, contain over 1000 different proteins and cellular constituents. In contrast, subunit vaccines are defined in composition and consist of either outer surface protein (Osp)A or OspA and an OspC chimeritope. In this study, we comparatively assessed antibody responses to OspA and OspC induced by vaccination with all canine bacterin and subunit LD vaccines that are commercially available in North America. Dogs were administered a two-dose series of the vaccine to which they were assigned (3 weeks apart): Subunit-AC, Subunit-A, Bacterin-1, and Bacterin-2. Antibody titers to OspA and OspC were determined by ELISA and the ability of each vaccine to elicit antibodies that recognize diverse OspC proteins (referred to as OspC types) assessed by immunoblot. While all of the vaccines elicited similar OspA antibody responses, only Subunit-AC triggered a robust and broadly cross-reactive antibody response to divergent OspC proteins. The data presented within provide new information regarding vaccination-induced antibody responses to key tick and mammalian phase antigens by both subunit and bacterin LD canine vaccine formulations.

Oral vaccination of dogs with a monovalent live-avirulent vaccine confers 1 year of immunity against Bordetella bronchiseptica challenge.

This experimental challenge study assessed immune protection 1 year after a single dose of live-attenuated oral Bordetella bronchiseptica (Bb) vaccine in dogs. Forty Bb-seronegative 7-9-week-old puppies were randomly assigned at Day 0 to receive a single oral dose of either Bb vaccine (n = 20; vaccinated group) or sterile water (n = 20; control group). Groups were housed separately until comingling 1 day pre-challenge (Day 365). Challenge with virulent aerosolized Bb occurred at Day 366. Clinical scores were obtained at Days 1-7, and 366-380. Bb microagglutination test (MAT) titers were obtained at Days -7, 0, monthly post-vaccination, and Days 358, 365, and 380. Nasal swabs were collected for microbiological assessment at Days -7, 0, 365, and 367-380. Oral Bb vaccination was not associated with side effects. Pre-challenge, vaccinated dogs developed persistent Bb MAT titers and control dogs remained seronegative. Post-challenge, duration of cough was longer in control dogs (least square means [LSM], 8.6 days) than vaccinated dogs (LSM, 1.5 days; P < 0.0001), with more control dogs having cough on 2 or more consecutive days (control group, n = 17/19, 89.5%; vaccinated group, n = 3/19, 15.8%; P = 0.0011). Post-challenge, Bb shedding occurred in all control dogs and 5/19 (26%) vaccinated dogs. Average duration of Bb shedding was longer in the control group (11.9 days vs. 0.6 days; P < 0.0001) and nasal Bb loads were higher in the control group (P < 0.00001). Orally administered Bb vaccine stimulated immunity that was still protective against virulent Bb challenge after 1 year.

Excluding non-English publications from evidence-syntheses did not change conclusions: a meta-epidemiological study.

OBJECTIVES: We aimed to assess whether limiting the inclusion criteria solely to English-language publications affected the overall conclusions of evidence syntheses. STUDY DESIGN AND SETTING: Our analyses used a dataset of a previous methods study that included 59 randomly selected Cochrane intervention reviews with no language restrictions. First, we ascertained the publication language of all 2,026 included publications. Next, we excluded studies based on the following criteria: (1) publication solely in non-English language, or (2) main publication (in case of multiple publications of the same study) in non-English language. We then re-calculated meta-analyses for outcomes that were presented in the main summary of findings tables of the Cochrane reports. If the direction of the effect estimate or the statistical significance changed, authors of the respective Cochrane reviews were consulted to assess whether the new evidence base would have changed their conclusions. The primary outcome of our analyses examined the proportion of conclusions that would change with the exclusion of non-English publications. We set the threshold for the approach as noninferior if the upper limit of the 95% confidence interval of the proportion of changed conclusions did not cross a margin of 10%. RESULTS: Across all 59 Cochrane reviews, 29 (49%) included 80 non-English publications. For 16 (27%) of these Cochrane reviews, the exclusion of non-English publications resulted in the exclusion of at least one study. In the remaining 13 Cochrane reviews, the non-English publications were not the only or main publication of the study or they did not contribute to the main summary of the findings table, so their exclusion did not result in an exclusion of the study. Overall, the exclusion of non-English publications led to the exclusion of 31 studies contributing to 40 outcomes. For 38 of the 40 outcomes, the exclusion of non-English studies did not markedly alter the size or direction of effect estimates or statistical significance. In two outcomes, the statistical significance changed, but authors would have still drawn the same conclusion, albeit with less certainty. Thus, the proportion of changed conclusions in our sample was 0.0% (95% CI 0.0-0.6), which indicated the noninferiority of the approach. However, the majority of excluded studies were small. CONCLUSION: Exclusion of non-English publications from systematic reviews on clinical interventions had a minimal effect on overall conclusions and could be a viable methodological shortcut, especially for rapid reviews.

Indications for induction of labour: a best-evidence review.

BACKGROUND: Rates of labour induction are increasing. OBJECTIVES: To review the evidence supporting indications for induction. SEARCH STRATEGY: We listed indications for labour induction and then reviewed the evidence. We searched MEDLINE and the Cochrane Library between 1980 and April 2008 using several terms and combinations, including induction of labour, premature rupture of membranes, post-term pregnancy, preterm prelabour rupture of membranes (PROM), multiple gestation, suspected macrosomia, diabetes, gestational diabetes mellitus, cardiac disease, fetal anomalies, systemic lupus erythematosis, oligohydramnios, alloimmunization, rhesus disease, intrahepatic cholestasis of pregnancy (IHCP), and intrauterine growth restriction (IUGR). We performed a review of the literature supporting each indication. SELECTION CRITERIA: We identified 1387 abstracts and reviewed 418 full text articles. We preferentially included high-quality systematic reviews or large randomised trials. Where no such studies existed, we included the best evidence available from smaller randomised trials and observational studies. MAIN RESULTS: We included 34 full text articles. For each indication, we assigned levels of evidence and grades of recommendation based upon the GRADE system. Recommendations for induction of labour for post-term gestation, PROM at term, and premature rupture of membranes near term with pulmonary maturity are supported by the evidence. Induction for IUGR before term reduces intrauterine fetal death, but increases caesarean deliveries and neonatal deaths. Evidence is insufficient to support induction for women with insulin-requiring diabetes, twin gestation, fetal macrosomia, oligohydramnios, cholestasis of pregnancy, maternal cardiac disease and fetal gastroschisis. AUTHORS' CONCLUSIONS: Research is needed to determine risks and benefits of induction for many commonly advocated clinical indications.

Reg-2 expression in dorsal root ganglion neurons after adjuvant-induced monoarthritis.

Reg-2 is a secreted protein that is expressed de novo in motoneurons, sympathetic neurons, and dorsal root ganglion (DRG) neurons after nerve injury and which can act as a Schwann cell mitogen. We now show that Reg-2 is also upregulated by DRG neurons in inflammation with a very unusual expression pattern. In a rat model of monoarthritis, Reg-2 immunoreactivity was detected in DRG neurons at 1 day, peaked at 3 days (in 11.6% of DRG neurons), and was still present at 10 days (in 5%). Expression was almost exclusively in the population of DRG neurons that expresses the purinoceptor P2X(3) and binding sites for the lectin Griffonia simplicifolia IB4, and which is known to respond to glial cell line-derived neurotrophic factor (GDNF). Immunoreactivity was present in DRG cell bodies and central terminals in the dorsal horn of the spinal cord. In contrast, very little expression was seen in the nerve growth factor (NGF) responsive and substance P expressing population. However intrathecal delivery of GDNF did not induce Reg-2 expression, but leukemia inhibitory factor (LIF) had a dramatic effect, inducing Reg-2 immunoreactivity in 39% of DRG neurons and 62% of P2X(3) cells. Changes in inflammation have previously been observed predominantly in the neuropeptide expressing, NGF responsive, DRG neurons. Our results show that changes also take place in the IB4 population, possibly driven by members of the LIF family of neuropoietic cytokines. In addition, the presence of Reg-2 in central axon terminals implicates Reg-2 as a possible modulator of second order dorsal horn cells.

Evolution of the male-determining gene SRY within the cat family Felidae.

In most placental mammals, SRY is a single-copy gene located on the Y chromosome and is the trigger for male sex determination during embryonic development. Here, we present comparative genomic analyses of SRY (705 bp) along with the adjacent noncoding 5' flank (997 bp) and 3' flank (948 bp) in 36 species of the cat family Felidae. Phylogenetic analyses indicate that the noncoding genomic flanks and SRY closely track species divergence. However, several inconsistencies are observed in SRY. Overall, the gene exhibits purifying selection to maintain function (omega = 0.815) yet SRY is under positive selection in two of the eight felid lineages. SRY has low numbers of nucleotide substitutions, yet most encode amino acid changes between species, and four different species have significantly altered SRY due to insertion/deletions. Moreover, fixation of nonsynonymous substitutions between sister taxa is not consistent and may occur rapidly, as in the case of domestic cat, or not at all over long periods of time, as observed within the Panthera lineage. The former resembles positive selection during speciation, and the latter purifying selection to maintain function. Thus, SRY evolution in cats likely reflects the different phylogeographic histories, selection pressures, and patterns of speciation in modern felids.

A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury.

Previous studies have shown that omega-3 polyunsaturated fatty acids such as alpha-linolenic acid and docosahexaenoic acid (DHA) are neuroprotective in models of spinal cord injury (SCI) in rodents. However, the mechanism of action underlying these effects has not been elucidated, and the optimum treatment regime remains to be defined. We have therefore carried out a detailed analysis of the effects of DHA in adult rats subject to thoracic compression SCI. Saline or DHA (250 nmol/kg) was administered intravenously (i.v.) 30 min after compression. After injury, the saline group received a standard control diet for 1 or 6 weeks, whereas DHA-injected animals received either a control or a DHA-enriched diet (400 mg/kg/day) for 1 or 6 weeks. Other groups received a DHA-enriched diet only for 1 week following injury, or received acute DHA (250 nmol/kg; i.v.) treatment delayed up to 3 h after injury. We also assessed oxidative stress and the inflammatory reaction at the injury site, neuronal and oligodendrocyte survival and axonal damage and the locomotor recovery. At 24 h, lipid peroxidation, protein oxidation, RNA/DNA oxidation and the induction of cyclooxygenase-2 were all significantly reduced by i.v. DHA administration. At 1 week and 6 weeks, macrophage recruitment was reduced and neuronal and oligodendrocyte survival was substantially increased. Axonal injury was reduced at 6 weeks. Locomotor recovery was improved from day 4, and sustained up to 6 weeks. Rats treated with a DHA-enriched diet in addition to the acute DHA injection were not significantly different from the acute DHA-treated animals at 1 week, but at 6 weeks showed additional improvements in both functional and histological outcomes. DHA treatment was ineffective if the acute injection was delayed until 3 h post-injury, or if the DHA was administered for 1 week solely by diet. Our results in a clinically relevant model of SCI show that significant neuroprotection can be obtained by combining an initial acute i.v. injection of DHA with a sustained dietary supplementation. Given that the safety and tolerability of preparations enriched in omega-3 fatty acids is already well-documented, such a combined DHA treatment regime deserves consideration as a very promising approach to SCI management.

Freezing resistance improvement of Lactobacillus reuteri by using cell immobilization.

Lactobacillus reuteri shows certain beneficial effects to human health and is recognized as a probiotic. However, its application in frozen foods is still not popular because of its low survival during freezing and frozen storage. Cell immobilization technique could effectively exert protection effects to microbial cells in order to enhance their endurance to unfavorable environmental conditions as well as to improve their viability and cell concentration. Ca-alginate and kappa-carrageenan were used to immobilize L. reuteri in this research, and the immobilized cells were exposed to different freezing temperatures, i.e. -20 degrees C, -40 degrees C, -60 degrees C, -80 degrees C, and stored at -40 degrees C and -80 degrees C for 12 weeks. The objectives were to study the protection effects of cell immobilization against the adverse conditions of freezing and frozen storage, and the effects of freezing temperatures to the immobilized cells. Cell immobilization was used to raise the survival of L. reuteri during freezing and frozen storage in order to develop frozen foods with the probiotic effects of L. reuteri. Results indicated that immobilized L. reuteri possessed better survival in both freezing and frozen storage. The survival of immobilized L. reuteri was higher than that of free cells, and the effects of lower freezing temperature were better than higher freezing temperature. The immobilization effects of Ca-alginate were found to be superior to kappa-carrageenan. Cell immobilized L. reuteri exhibits potential to be used in frozen foods.

Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology.

Hypervascularity, focal necrosis, persistent cerebral edema, and rapid cellular proliferation are key histopathologic features of glioblastoma multiforme (GBM), the most common and malignant of human brain tumors. By immunoperoxidase and immunofluorescence, we definitively have demonstrated the presence of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFr) in five out of five human glioma cell lines (U-251MG, U-105MG, D-65MG, D-54MG, and CH-235MG) and in eight human GBM tumor surgical specimens. In vitro experiments with glioma cell lines revealed a consistent and reliable relation between EGFr activation and VEGF production; namely, EGF (1-20 ng/ml) stimulation of glioma cells resulted in a 25-125% increase in secretion of bioactive VEGF. Conditioned media (CM) prepared from EGF-stimulated glioma cell lines produced significant increases in cytosolic free intracellular concentrations of Ca2+ ([Ca2+]i) in human umbilical vein endothelial cells (HUVECs). Neither EGF alone or CM from glioma cultures prepared in the absence of EGF induced [Ca2+]i increases in HUVECs. Preincubation of glioma CM with A4.6.1, a monoclonal antibody to VEGF, completely abolished VEGF-mediated [Ca2+]i transients in HUVECs. Likewise, induction by glioma-derived CM of von Willebrand factor release from HUVECs was completely blocked by A4.6.1 pretreatment. These observations provide a key link in understanding the basic cellular pathophysiology of GBM tumor angiogenesis, increased vascular permeability, and cellular proliferation. Specifically, EGF activation of EGFr expressed on glioma cells leads to enhanced secretion of VEGF by glioma cells. VEGF released by glioma cells in situ most likely accounts for pathognomonic histopathologic and clinical features of GBM tumors in patients, including striking tumor angiogenesis, increased cerebral edema and hypercoagulability manifesting as focal tumor necrosis, deep vein thrombosis, or pulmonary embolism.

Characterization of non-neuronal elements within fibronectin mats implanted into the damaged adult rat spinal cord.

Previous studies have shown that mats made from fibronectin (FN) integrate well into spinal cord lesion sites and support extensive axonal growth. Using immunohistochemistry, we have investigated the non-neuronal factors that contribute to these properties. Extensive vascularization was observed in FN mats by 1 week along with heavy macrophage infiltration by 3 days post-implantation. By 1 week post-implantation, laminin tubules had formed and were associated with axons and p75 immunoreactive Schwann cells. By 4 weeks post-implantation, most axons were associated with Schwann cell derived myelin. Few oligodendrocytes were present within the mat, even with an increase in the number of oligodendrocyte precursors around the implant site by 7 days post-implantation. Astrocyte proliferation also occurred in the intact tissue, with a prominent glial scar forming around the implant within 4 weeks. However, by 2 months post-implantation astrocytes were present in the FN implant site and were intermingled with the axons. Axonal ingrowth and integration of the FN mats is probably due to the ability of FN mats to support and organize infiltration of Schwann cells and deposition of laminin. At later time points, myelinated axons remain in the implant site, even after other elements (e.g. macrophages and laminin) have disappeared. Both of these properties are likely to be important in the design of biomaterial bridges for CNS regeneration.

Interleukin generation in experimental colon cancer of rats: effects of tumor growth and tumor therapy.

The capacity of inbred W/Fu rats bearing syngeneic colon carcinomas to generate interleukin(s) (IL) was studied during primary tumor growth, after tumor resection, and during postresection immunotherapy. During local tumor growth, there was a significant decrease in the capacity of the host's adherent mononuclear cells to generate IL-1 and of peripheral blood mononuclear cells to generate IL-2 (16.6 and 23%, respectively, when compared to control animals; P less than .01). The presence of regional metastases or large primary tumor burden resulted in a further sharp fall in IL generation (0.9 and 10% for IL-1 and IL-2, respectively, when compared to control animals; P less than .01). With the use of three different doses of tumor inoculum, inhibition of IL generation was shown to occur when tumors were barely palpable. Decrease in IL correlated with tumor growth and not with the initial number of tumor cells injected. Tumor resection resulted in a rise in IL-2 generation from 36 to 64% of control animals' levels. Postresection immunotherapy with the use of an active specific immunization protocol successfully modulated IL-2 production to normal in animals protected from tumor recurrence. Animals that developed recurrent tumors despite immunization exhibited a continued inability to generate IL (mean values of IL-2 production compared to controls: 184% in animals free of recurrence after immunotherapy, 1% in animals developing recurrent tumors after immunotherapy; P less than .01). These results suggested that alterations in IL generation may lead to immune unresponsiveness during tumor growth. Active specific immunotherapy protecting animals from recurrence after primary tumor resection may be predicated on the successful modulation of IL level generation by host immunocytes.

Effects of specific active immunization on tumor recurrence following primary tumor resection in WF rats with 1,2-dimethylhydrazine-induced bowel cancer.

Primary gastrointestinal tumors were induced in male WF rats by 16 weekly sc injections of 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8; 20 mg/kg/wk]. Twenty-four to 28 weeks after the start of DMH injections, all rats were surgically explored and gastrointestinal tumors were resected. Rats with no remaining microscopic disease after operation were immunized with one of four tumor isografts. The first isograft, DMH-W163, is a poorly differentiated mucinous adenocarcinoma explanted from a colon cancer in a DMH-treated animal. It has been shown to possess antigens that cross-react with other DMH-induced bowel adenocarcinoma isografts. The second isograft, DMH-W49, is a carcinosarcoma explanted from a DMH-treated primary colon cancer. It has intermediate antigenic cross-reactivity with other colon adenocarcinoma isografts in the WF model. The third isograft, DMH-W15, is a sarcoma explanted from a DMH-induced colon cancer that does not possess antigens cross-reactive with other DMH-induced colon adenocarcinomas. The fourth isograft, SPK, is a spontaneous (non-DMH-induced) renal cell carcinoma that is immunogenic but should not contain tissue-type-specific antigens cross-reacting with the bowel cancers. Immunized rats received three sc weekly injections of 1 X 10(3) irradiated cells. Concomitant control rats received no immunization after resection of the primary tumor. Within 24 weeks of primary tumor resection, 12 of 16 (75%) rats not immunized had tumor recurrence. Only 8 of 24 (34%) rats immunized with DMH-W163 had tumor recurrence (P less than .025 compared to controls). Fifty percent of animals (10/20) immunized with the carcinosarcoma DMH-W49 had a recurrence. Animals immunized with the non-cross-reacting DMH-W15 sarcoma isograft had a recurrence rate similar to that of controls (16/20, 75%). The rats immunized with SPK were not protected from recurrence. Twelve of 19 (63%) had a recurrence at or near the suture line within 24 weeks following primary tumor resection. These results confirm that adjuvant immunotherapy can decrease the rate of recurrence following primary tumor resection in this model. In addition, immunogens that possessed tissue-type-specific antigens were more effective in preventing tumor recurrence than those that did not.