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Joyce S Ramos,1,2 Lance C Dalleck,2,3 Rebecca C Stennett,1 Gregore I Mielke,1 Shelley E Keating,1 Lydia Murray,4 Sumaira Z Hasnain,4,5 Robert G Fassett,1 Michael McGuckin,4,6 Ilaria Croci,1,7 Jeff S Coombes1 1Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Queensland, Australia; 2Caring Futures Institute and SHAPE Research Centre, Exercise Science and Clinical Exercise Physiology, College of Nursing and Health Sciences, Flinders University, Adelaide, South Australia, Australia; 3Recreation, Exercise, and Sport Science Department, Western State Colorado University, Gunnison, Colorado, USA; 4Immunopathology Group, Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia; 5Australian Infectious Disease Research Centre, University of Queensland, Brisbane, Queensland, Australia; 6Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia; 7K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Sor Trondelag, NorwayCorrespondence: Joyce S Ramos Email joyce.ramos@flinders.edu.auIntroduction: IL-22 may have a role in the alleviation of the metabolic syndrome (MetS) via protection of pancreatic beta and endothelial cells from oxidative and lipid-induced damage. We aimed to investigate the effects of moderate-intensity continuous training (MICT) and different volumes of high-intensity interval training (HIIT) on changes in circulating IL-22.Methods: This was a sub-study of the “Exercise in the prevention of Metabolic Syndrome” (EX-MET) a multi-center, randomized trial. This study used data collected at the Brisbane site. Thirty-nine individuals with MetS were randomized to one of three 16-wk interventions: 1) MICT (n=10, 30min at 60– 70% HR peak, 5x/wk); 2) 4HIIT (n=13, 4x4min at 85– 95% HR peak, interspersed with 3min of active recovery at 50– 70% HR peak, 3x/wk); or 3) 1HIIT (n=16, 1x4min at 85– 95% HR peak, 3x/wk). Serum IL-22 concentration was measured following a 12-hr fast via an enzyme linked immunosorbent assay, before and after the intervention. MetS severity, insulin resistance (IR), visceral adipose tissue (VAT), and cardiorespiratory fitness (CRF) were also measured via MetS z-score, HOMA-IR, dual-energy X-ray absorptiometry, and indirect calorimetry (maximal exercise test), respectively.Results: The median (IQR) IL-22% changes from pre- to post-intervention in the MICT, 4HIIT, and 1HIIT groups were − 17% (− 43.0% to 31.3%), +16.5% (− 18.9% to 154.9%), and +15.9% (− 28.7% to 46.1%), respectively. Although there were no significant between-group differences in IL-22 concentration change, there was a medium-to-large group × time interaction effect [F(2,35)=2.08, p=0.14, η2=0.14].Conclusion: Although there was no statistically significant between-group difference in IL-22 change, the study suggests that different exercise intensities may have opposing effects on IL-22 concentration in individuals with MetS.Keywords: high-intensity interval training, IL-22, inflammation, cardiovascular disease, metabolic syndrome, cytokine

Superconductivity and spin-orbit (SO) interaction have been two separate emerging fields until very recently that the correlation between them seemed to be observed. However, previous experiments concerning SO coupling are performed far beyond the superconducting state and thus a direct demonstration of how SO coupling affects superconductivity remains elusive. Here we investigate the SO coupling in the critical region of superconducting transition on Al nanofilms, in which the strength of disorder and spin relaxation by SO coupling are changed by varying the film thickness. At temperatures T sufficiently above the superconducting critical temperature Tc, clear signature of SO coupling reveals itself in showing a magneto-resistivity peak. When Tc, the resistivity peak can still be observed; however, its line-shape is now affected by the onset of the quasi two-dimensional superconductivity. By studying such magneto-resistivity peaks under different strength of spin relaxation, we highlight the important effects of SO interaction on superconductivity. [ABSTRACT FROM AUTHOR]

The generation of antitumour immunity depends on the nature of dendritic cell (DC)-tumour interactions. These have been studied mostly by using in vitro-derived DC which may not reflect the natural biology of DC in vivo. In breast cancer, only one report has compared blood DC at different stages and no longitudinal evaluation has been performed. Here we conducted three cross-sectional and one one-year longitudinal assessments of blood DC in patients with early (stage I/II, n=137) and advanced (stage IV, n=36) disease compared to healthy controls (n=66). Patients with advanced disease exhibit markedly reduced blood DC counts at diagnosis. Patients with early disease show minimally reduced counts at diagnosis but a prolonged period (1 year) of marked DC suppression after tumour resection. While differing in frequency, DC from both patients with early and advanced disease exhibit reduced expression of CD86 and HLA-DR and decreased immunostimulatory capacities. Finally, by comparing a range of clinically available maturation stimuli, we demonstrate that conditioning with soluble CD40L induces the highest level of maturation and improved T-cell priming. We conclude that although circulating DC are compromised by loco-regional and systemic breast cancer, they respond vigorously to ex vivo conditioning, thus enhancing their immunostimulatory capacity and potential for immunotherapy. [ABSTRACT FROM AUTHOR]

Cytokines are important for breast cell function, both as trophic hormones and as mediators of host defense mechanisms against breast cancer. Recently, inducible feedback suppressors of cytokine signalling (SOCS/JAB/SSI) have been identified, which decrease cell sensitivity to cytokines. We examined the expression of SOCS genes in 17 breast carcinomas and 10 breast cancer lines, in comparison with normal tissue and breast lines. We report elevated expression of SOCS-1-3 and CIS immunoreactive proteins within in situ ductal carcinomas and infiltrating ductal carcinomas relative to normal breast tissue. Significantly increased expression of SOCS-1-3 and CIS transcripts was also shown by quantitative in situ hybridisation within both tumour tissue and reactive stroma. CIS transcript expression was elevated in all 10 cancer lines, but not in control lines. However, there was no consistent elevation of other SOCS transcripts. CIS protein was shown by immunoblot to be present in all cancer lines at increased levels, mainly as the 47 kDa ubiquitinylated form. A potential proliferative role for CIS overexpression is supported by reports that CIS activates ERK kinases, and by strong induction in transient reporter assays with an ERK-responsive promoter. The in vivo elevation of SOCS gene expression may be part of the host/tumour response or a response to autocrine/paracrine GH and prolactin. However, increased CIS expression in breast cancer lines appears to be a specific lesion, and could simultaneously shut down STAT 5 signalling by trophic hormones, confer resistance to host cytokines and increase proliferation through ERK kinases. [ABSTRACT FROM AUTHOR]

Abstract Background The MAL2 gene, encoding a four-transmembrane protein of the MAL family, is amplified and overexpressed in breast and other cancers, yet the significance of this is unknown. MAL-like proteins have trafficking functions, but their molecular roles are largely obscure, partly due to a lack of known binding partners. Methods Yeast two-hybrid screening of a breast carcinoma cDNA expression library was performed using a full-length MAL2 bait, and subsequent deletion mapping experiments were performed. MAL2 interactions were confirmed by co-immunoprecipitation analyses and confocal microscopy was employed to compare protein sub-cellular distributions. Sucrose density gradient centrifugation of membranes extracted in cold Triton X-100 was employed to compare protein distributions between Triton X-100-soluble and -insoluble fractions. Results The tumor-associated protein mucin 1 (MUC1) was identified as a potential MAL2 partner, with MAL2/MUC1 interactions being confirmed in myc-tagged MAL2-expressing MCF-10A cells using co-immunoprecipitation assays. Deletion mapping experiments demonstrated a requirement for the first MAL2 transmembrane domain for MUC1 binding, whereas the MAL2 N-terminal domain was required to bind D52-like proteins. Confocal microscopy identified cytoplasmic co-localisation of MUC1 and MAL2 in breast cell lines, and centrifugation of cell lysates to equilibrium in sucrose density gradients demonstrated that MAL2 and MUC1 proteins were co-distributed between Triton X-100-soluble and -insoluble fractions. However co-immunoprecipitation analyses detected MAL2/MUC1 interactions in Triton X-100-soluble fractions only. Myc-MAL2 expression in MCF-10A cells was associated with both increased MUC1 detection within Triton X-100-soluble and -insoluble fractions, and increased MUC1 detection at the cell surface. Conclusion These results identify MUC1 as a novel MAL2 partner, and suggest a role for MAL2 in regulating MUC1 expression and/or localisation.

The transition from late pregnancy (LP) to early lactation (EL) in dairy cows is characterized by a major reorganization of the metabolic activities of liver and adipose tissue in support of milk synthesis. This reorganization has been attributed in large part to variation in the plasma concentration and actions of growth hormone, insulin, and other metabolic hormones. A role for the immune system has also been suggested by a near-universal rise in circulating levels of liver-derived acute-phase proteins (APP) in early lactating cows. However, less attention has been devoted to the possibility that resident macrophages of liver and adipose tissue adopt a proinflammatory state (referred herein as inflammatory tone) in parallel with the rise in plasma APP. We addressed this question by measuring the expression of genes expressed predominantly in the resident macrophage population of liver and adipose tissue and indicative of a proinflammatory (tumor necrosis factor α, IL-6, IL-12, resistin, and cluster of differentiation 80 [CD80]) or anti-inflammatory state (IL-10 and chitinase-3-like protein 1 [CHI3L1]). In a first group of cows, none of these inflammatory gene markers were regulated in liver between LP on d -29 (relative to parturition) and on d 8 of EL despite 1.7 to 5.6-fold upregulation in the expression of the APP (haptoglobin, serum amyloid α, and orosomucoid 1). In a second group of healthy cows, expression of the inflammatory gene markers did not differ between livers with low (<5.3%) or high (>11.5%) triglyceride content on d 7 of EL. In adipose tissue, a modest increase in inflammatory tone was suggested between LP and EL by increased CD80 expression and decreased CHI3L1 expression in EL. To assess the possibility that inflammatory tone would be more prominent if assayed in a cell compartment enriched with macrophages, adipose tissue was obtained in LP on d -28 and in EL on d +10 from cows experiencing a healthy transition period and fractionated into its adipocyte and stromal vascular cell (SVC) compartments. Expression of inflammatory gene markers was higher in SVC than adipocytes but remained unregulated in SVC between LP and EL. Overall, these results suggest little change in the inflammatory tone of resident macrophages in liver and adipose tissue of healthy transition dairy cows and do not support a role for the local immune system in the reorganization of metabolism in these tissues at the onset of lactation., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Site specific oral delivery of many biopharmaceutical classification system (BCS) class II and IV drugs is challenging due to their poor solubility, low permeability and degradation in the gastrointestinal tract. Whilst colloidal carriers have been used to improve the bioavailability of such drugs, most nanocarriers based drug delivery systems suffer from multiple disadvantages, including low encapsulation efficiency (liposomes, polymeric nanoparticles), complex synthesis methods (silica, silicon-based materials) and poorly understood biodegradability (inorganic nanoparticles). Herein, a novel pH responsive nanocolloids were self-assembled using natural compounds such as bovine β-lactoglobulin (BLG) and succinylated β-lactoglobulin (succ. BLG) cross-linked with epsilon poly l-lysine (BCEP and BCP), and found to possess high loading capacity, high aqueous solubility and site-specific oral delivery of a poorly soluble nutraceutical (curcumin), improving its physicochemical properties and biological activity in-vitro and ex-vivo. Our optimized synthesis formed colloids of around 200 nm which were capable of encapsulating curcumin with ~100% encapsulation efficiency and ~10% w/w drug loading. By forming nanocomplexes of curcumin with BLG and succ. BLG, the aqueous solubility of curcumin was markedly increased by ~160-fold and ~86-fold, respectively. Encapsulation with BLG increased the solubility, whereas succ. BLG prevent release of encapsulated curcumin when subjected to gastric fluids as it is resistant to breakdown on exposure to pepsin at acidic pH. In conditions mimicking the small intestine, Succ. BLG was more soluble resulting in sustained release of the encapsulated drug at pH 7.4. Additionally, crosslinking succ. BLG with E-PLL significantly enhanced curcumin's permeability in an in-vitro Caco-2 cell monolayer model compared to curcumin solution (dissolved in 1% DMSO), or non-crosslinked BLG/succ. and BLG. In a mouse-derived intestinal epithelial 3D organoid culture stimulated with IL-1β, BLG-CUR and crosslinked BCEP nanoparticles reduced the production of inflammatory cytokines and chemokines such as Tnfα and Cxcl10 more than curcumin solution or suspension while these nanoparticles were non-toxic to organoids. Overall this work demonstrates the promise of nutraceutical-based hybrid self-assembled colloidal system to protect hydrophobic drugs from harsh gastrointestinal conditions and improve their solubility, dissolution, permeability and biological activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dairy cows consume inadequate amounts of feed in early lactation and during conditions and diseases such as excessive fatness, heat stress, and infectious diseases. Affected cows often experience increases in plasma concentrations of acute phase proteins consistent with the negative effect of inflammation on appetite. The acute phase protein orosomucoid 1 (ORM1), also known as alpha-1-acid glycoprotein, was recently reported to reduce appetite in the mouse through its ability to bind the full-length leptin receptor (Ob-Rb) and activate appetite-suppressing signal transducer and activator of transcription 3 (STAT3) signaling. These observations raise the possibility that ORM1 exerts appetite-suppressing effects in dairy cattle during periods of increased inflammatory tone. The applicability of this model was assessed in 2 ways. First, we asked whether ORM1 is regulated during periods of inadequate appetite such as the transition from late pregnancy to early lactation and periods of increased inflammatory tone. Plasma ORM1 was invariant in late pregnancy but increased 2.5-fold between parturition and d 7 of lactation. Gene expression studies showed that liver was the major source of this elevation with little contribution by adipose tissue or mammary gland. Additional studies showed that plasma ORM1 was not increased further by excessive fatness or by reproductive dysfunction in early lactation and was completely unresponsive to inflammatory stimuli such as heat stress or intravascular administration of the endotoxin lipopolysaccharide during established lactation. Second, we tested the ability of ORM1 to trigger STAT3 signaling through Ob-Rb using Chinese hamster ovary K1 (CHO-K1) cells transfected with a STAT3 expression plasmid. In this configuration, CHO-K1 cells did not express Ob-Rb and were incapable of leptin-induced STAT3 phosphorylation. Leptin responsiveness was conferred by co-transfecting with bovine Ob-Rb, with leptin causing increases of 5.7-fold in STAT3 phosphorylation and 2.1-fold in the expression of the STAT3-dependent gene, SOCS3. In contrast, neither bovine or human ORM1 triggered STAT3 phosphorylation irrespective of dose and period of incubation tested. In summary, bovine ORM1 is not increased during periods of increased inflammatory tone except in early lactation and is incapable of Ob-Rb-dependent STAT3 signaling. Overall, these data are inconsistent with ORM1 mediating the appetite-suppressing effects of inflammation in cattle through Ob-Rb., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The polyphenolic compound resveratrol has received significant attention due to its many pharmacological actions such as anti-cancer, anti-inflammatory, antioxidant and antimicrobial activities. However, poor solubility and stability are major impediments for resveratrol's clinical effectiveness. In this work we have encapsulated resveratrol into soy protein isolate nanoparticles using a simple rotary evaporation technique. Resveratrol-loaded nanoparticles were around 100nm in diameter and negatively charged. Nano-encapsulated resveratrol was found to be in amorphous form and showed more than two times higher solubility with significantly increased dissolution when compared to free resveratrol. Finally, an in-vitro NF-κB inhibition assay revealed that encapsulated resveratrol was stable and retained bioactivity. This new formulation of resveratrol has the potential to boost the clinical effectiveness of this drug and could be utilised for other poorly soluble hydrophobic drugs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The naturally occurring polyphenol resveratrol (RES) has attracted increasing attention in recent years due to its antioxidant, anti-inflammatory, and anticancer activity. However, resveratrol's promising potential as a nutraceutical is hindered by its poor aqueous solubility, which limits its biological activity. Here we show that encapsulating resveratrol in colloidal mesoporous silica nanoparticles (MCM-48-RES) enhances its saturated solubility by ∼95% and increases its in vitro release kinetics compared to pure resveratrol. MCM-48-RES showed high loading capacity (20% w/w) and excellent encapsulation efficiency (100%). When tested against HT-29 and LS147T colon cancer cell lines, MCM-48-RES-mediated in vitro cell death was higher than that of pure resveratrol, mediated via the PARP and cIAP1 pathways. Finally, MCM-48-RES treatment also inhibited lipopolysaccharide-induced NF-κB activation in RAW264.7 cells, demonstrating improved anti-inflammatory activity. More broadly, our observations demonstrate the potential of colloidal mesoporous silica nanoparticles as next generation delivery carriers for hydrophobic nutraceuticals., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Public reporting of healthcare-associated infections is pervasive, with 33 states and the District of Columbia mandating public disclosure. We surveyed hospital epidemiologists on the perceived value of state public reports. Respondents believed consumers are unaware and do not consider the information important, but they indicated that epidemiologists have a role in consumer education.

Development of the pathologies associated with Helicobacter pylori infection, most seriously gastric adenocarcinoma, are a consequence of chronic inflammation, which both host and pathogen go to some lengths to minimize. Recently, we presented evidence that H. pylori can suppress the development of inflammation in its immediate microenvironment in the gastric mucosa of 129/Sv mice. We have now extended this study by showing that H. felis, a gastric colonizing Helicobacter closely related to H. pylori, does not possess the same ability to suppress Helicobacter-induced gastritis in mice. Differences between these bacterial species may provide clues as to the mechanism behind the inflammation-regulating ability of H. pylori. Moreover, our demonstration that H. pylori but not H. felis can locally suppress inflammation in vivo may explain why H. felis infection induces superior levels of gastritis as compared with H. pylori infection of mice.

Transmembrane mucins are glycoproteins involved in barrier function in epithelial tissues. To identify novel transmembrane mucin genes, we performed a tblastn search of the GenBanktrade mark EST data bases with a serine/threonine-rich search string, and a rodent gene expressed in bone marrow was identified. We determined the cDNA sequence of the human orthologue of this gene, MUC13, which localizes to chromosome band 3q13.3 and generates 3.2-kilobase pair transcripts encoding a 512-amino acid protein comprised of an N-terminal mucin repeat domain, three epidermal growth factor-like sequences, a SEA module, a transmembrane domain, and a cytoplasmic tail (GenBanktrade mark accession no. ). MUC13 mRNA is expressed most highly in the large intestine and trachea, and at moderate levels in the kidney, small intestine, appendix, and stomach. In situ hybridization in murine tissues revealed expression in intestinal epithelial and lymphoid cells. Immunohistochemistry demonstrated the human MUC13 protein on the apical membrane of both columnar and goblet cells in the gastrointestinal tract, as well as within goblet cell thecae, indicative of secretion in addition to presence on the cell surface. MUC13 is cleaved, and the beta-subunit containing the cytoplasmic tail undergoes homodimerization. Including MUC13, there are at least five cell surface mucins expressed in the gastrointestinal tract.

p73 has recently been identified as a structural and functional homolog of the tumor suppressor protein p53. Overexpression of p53 activates transcription of p53 effector genes, causes growth inhibition and induced apoptosis. We describe here the effects of a tumor-derived truncated transcript of p73alpha (p73Deltaexon2) on p53 function and on cell death. This transcript, which lacks the acidic N-terminus corresponding to the transactivation domain of p53, was initially detected in a neuroblastoma cell line. Overexpression of p73Deltaexon2 partially protects lymphoblastoid cells against apoptosis induced by anti-Fas antibody or cisplatin. By cotransfecting p73Deltaexon2 with wild-type p53 in the p53 null line Saos 2, we found that this truncated transcript reduces the ability of wild-type p53 to promote apoptosis. This anti-apoptotic effect was also observed when p73Deltaexon2 was co-transfected with full-length p73 (p73alpha). This was further substantiated by suppression of p53 transactivation of the effector gene p21/Waf1 in p73Deltaexon2 transfected cells and by inhibition of expression of a reporter gene under the control of the p53 promoter. Thus, this truncated form of p73 can act as a dominant-negative agent towards transactivation by p53 and p73alpha, highlighting the potential implications of these findings for p53 signaling pathway. Furthermore, we demonstrate the existence of a p73Deltaexon2 transcript in a very significant proportion (46%) of breast cancer cell lines. However, a large spectrum of normal and malignant tissues need to be surveyed to determine whether this transdominant p73 variant occurs in a tumor-specific manner.

Particular mucinous phenotypes have been associated with serrated epithelial polyps of the colon. These polyps also show a high frequency of DNA instability. The aim of this study was to examine the expression of mucins in colorectal cancers that arise through the suppressor and mutator pathways. The immunohistochemical distribution of the human apomucins MUC1, MUC2, MUC4, and MUC5AC was determined in 93 sporadic colorectal cancers classified previously (J. R. Jass et al., J. Clin. Pathol., 52: 455-460, 1999) according to levels of DNA microsatellite instability (MSI) as 22 MSI-high (MSI-H), 24 MSI-low (MSI-L), and 47 MS stable (MSS). MUC2 expression was observed in 19 (86%) MSI-H, 10 (42%) MSI-L, and 15 (32%) MSS cancers (P = 0.0001); and MUC5AC expression was observed in 17 (77%) MSI-H, 8 (33%) MSI-L, and 13 (28%) MSS cancers (P = 0.0003). There was no association between MUC1 or MUC4 expression and MSI status. The mucinous phenotype described in serrated polyps (MUC2+/MUC5AC+) was seen in 15 (68%) of 22 MSI-H and only 10 (14%) of 71 MSI-L/MSS cancers (P < 0.0001). Increased expression of the secretory mucins MUC2 and MUC5AC was observed in sporadic MSI-H cancers. Identical mucin changes and DNA MSI occurred in serrated polyps of the colorectum, which suggests that these lesions may represent precursors of MSI-H cancers.

Retrospective chart review of 1,702 patients undergoing laparoscopic cholecystectomy (LC) revealed an overall infection rate of 2.3% and a surgical-site infection rate of 0.4%. Preoperative antimicrobial prophylaxis was received by 79% of patients, but only 33% of these received the agent within 1 hour or less prior to surgery. These facts suggest that antimicrobial prophylaxis may not be necessary for low-risk LC patients.

Epithelial mucins are large, secreted and cell surface glycoproteins involved in epithelial cell protection, adhesion modulation, and signaling. Using differential display, we have identified two novel mucin cDNAs (dd34 and dd29), hereafter designated MUC11 and MUC12, respectively, that are down-regulated in colorectal cancers. Northern blots demonstrated polydisperse signals characteristic of mucin transcripts in RNA from normal colon that were absent in colorectal cancer. Both cDNAs were mapped by fluorescence in situ hybridization to chromosome band 7q22, the location of the MUC3 mucin gene, thus suggesting that there may be a cluster of mucin genes at this locus. The sequences of both differential display clones were extended by a combination of screening libraries and PCR. The 2.8-kb MUC11 cDNA composite encoded 35 serine/threonine-rich, mucin-like degenerate 28 amino acid tandem repeats. The MUC12 cDNA composite encoded a putative transmembrane mucin containing two extracellular cysteine-rich, EGF-like domains, a coiled-coil region, and a mucin-like domain consisting of 28 amino acid degenerate tandem repeats. Distinct patterns of expression of MUC11, MUC12, and MUC3 mRNAs were observed in a range of normal human tissues. MUC12 mRNA was not expressed in any of six colorectal cancer cell lines examined and was down-regulated or absent in 6 of 15 (40%) tumors compared with matched normal colonic tissue. In contrast, MUC11 showed a different pattern of mRNA expression, with four of these lines showing low levels and the other two lines showing relatively high levels of MUC11 transcripts. Expression of MUC11 was down-regulated in the tumors of 12 of 15 (80%) paired samples. Structural homology of MUC12 with rat, mouse, and human MUC3 and human and rat MUC4/ASGP2 indicate that there is a distinct subfamily of transmembrane mucins with conserved epidermal growth factor domains. The homology of MUC12 with epidermal growth factor-like growth factors and its down-regulation in colorectal cancers, together with known interactions between rat MUC4 and c-erbB-2 growth factor receptors, suggests that MUC12 may be involved in epithelial cell growth regulation.

We studied the distribution of the four human apomucins MUC1, MUC2, MUC4, and MUC5AC in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum using immunohistochemical techniques, with the aim of comparing and contrasting their patterns of expression. A series of 12 hyperplastic polyps, 27 serrated adenomas, and 20 traditional adenomas was studied. No significant change in apomucin expression was observed in traditional adenomas compared with normal colorectal epithelium, except for MUC5AC, which was present in 12 of the adenomas (60%) and only 20% of the normal samples. In both hyperplastic polyps and serrated adenomas, MUC2 and MUC5AC mucin expression was consistently and markedly increased. In 50% of the hyperplastic polyps, MUC4 was reduced but in the remaining cases was similar to normal. Loss of MUC4 expression was observed in all serrated adenomas. MUC1 was not increased in the hyperplastic polyps but increased expression was seen in 17 of the serrated adenomas (63%). Similar altered distribution patterns of MUC2, MUC4, and MUC5AC were seen in hyperplastic polyps and serrated adenomas, whereas traditional adenomas showed little change from normal patterns of expression. Although hyperplastic polyps are commonly defined as benign lesions without neoplastic potential, the similar phenotypes of hyperplastic and serrated adenomas and the existence of mixed polyps suggest that these lesions may represent a histogenetic continuum.

Background: The reproductive hormone inhibin has been used as a diagnostic marker of ovarian mucinous and granulosa cell cancers. The aims of this study were to develop a new inhibin immunofluorometric assay (alphaC IFMA) to replace an inhibin RIA as a diagnostic marker of these ovarian cancers and to assess whether the alphaC IFMA in combination with CA125, which detects serous cancers, leads to an improved biochemical diagnosis of all ovarian cancers., Methods: Serum inhibin concentrations were determined in healthy postmenopausal women (n = 165) and women with ovarian cancers (n = 154), using an inhibin RIA and an alphaC IFMA, which detects inhibin forms containing the alphaC subunit as well as the free alphaC subunit., Results: The alphaC IFMA gave a similar or better discrimination of mucinous (90% vs 71%) and granulosa cell (100% vs 100%) cancers compared with the inhibin RIA. Combination of CA125 and alphaC IFMA values by canonical variate analysis or by multiROC analysis showed that the percentage of all ovarian cancers detected was significantly increased compared with either CA125 or alphaC IFMA alone., Conclusions: The alphaC IFMA shows a similar or better specificity compared with the RIA, but with increased sensitivity. In combination with CA125, the alphaC IFMA provides an effective dual test for the detection of the majority (90%) of ovarian cancers., (Copyright 1999 American Association for Clinical Chemistry.)

Purpose: Examine changing patient characteristics and surgical outcomes for patients undergoing cholecystectomy at five community hospitals in 1989 and 1993., Procedures: In a retrospective chart review, data were gathered regarding gallstone disease severity, type of admission, patient age, number of comorbidities, American Society of Anesthesiologists (ASA) Physical Status Classification, length of stay, and multiple outcomes of surgery., Main Findings: The volume of nonincidental cholecystectomies increased 26%, from 1611 in 1989 to 2031 in 1993. Nearly all of the increase occurred among patients with uncomplicated cholelithiasis and with elective admissions. In 1993, lengths of stay were significantly shorter and percentages of complications were significantly lower for infectious, cardiac, pulmonary, and gastrointestinal complications when controlling for patient case-mix characteristics. There were more major intraoperative complications (unintended wounds or injuries to the common bile duct, bowel, blood vessel(s), or other organs) in 1993., Conclusions: Different types of patients underwent cholecystectomy in 1993 compared with patients in 1989, which supports the hypothesis of changing thresholds. Statements supporting the safety of cholecystectomy in the laparoscopic era were borne out when controlling for differences in patient characteristics.

In view of the potential uses of cell surface tumour associated antigens in novel anticancer treatment, a study was designed to investigate whether the biological response modifiers interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) could effect the expression of an epitope on the tumour associated MUC1 epithelial mucin. Four ovarian carcinoma cell lines showing high (OAW42 and GG) and low (JAM and PE01) basal expression of MUC1 were treated with 10-1000 U/mL of IFN-gamma or TNF-alpha for one or five days. Changes in MUC1 expression in cells exposed to IFN-gamma or TNF-alpha were monitored using an ELISA technique with the monoclonal antibody BC2 which reacts with a core protein epitope on the MUC1 mucin, and then corrected for the number of viable cells present. TNF-alpha had little effect on MUC1 expression, but one or five days exposure to IFN-gamma significantly increased MUC1 expression (p < 0.01) in all cell lines including the two cell lines that initially showed little or no expression.

This study aimed to investigate whether the biological response modifiers (BRM) interferon gamma (IFN gamma) and tumour necrosis factor alpha (TNF alpha) could enhance the cytotoxic action of cisplatin on ovarian tumour cells in vitro. The sensitivity of four cell lines (OAW42, GG, JAM and PE01) to drugs and drug combinations was tested by a radiolabelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each of the BRM. When IFN gamma was used in combination with cisplatin, a significant enhancement of cisplatin toxicity occurred in three of four cell lines. TNF alpha demonstrated such an effect in two cell lines but diminished the toxicity of cisplatin in one cell line. A purely additive effect of the agents may explain the enhanced toxicity of cisplatin in some of these cases. However, in one cell line at least (PEO1), both TNF alpha and IFN gamma demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may provide better antitumour regimen than cisplatin alone in some patients with ovarian cancer, but the response is likely to be heterogeneous between patients.

This study sought to produce monoclonal antibodies (MAbs) which reacted with the MUC2 core protein. Two MAbs [3A2 (IgG1) and 4F1 (IgM)] were produced by immunising female BALB/c mice with gel-formed mucin from the LS174T colon cancer cell line followed by a KLH conjugate of a 29 amino acid synthetic peptide whose sequence was derived from the variable number of tandem repeats (VNTR) region of a MUC2 cDNA clone. The MAbs reacted with synthetic MUC2 VNTR peptides but not synthetic MUC1 or MUC3 VNTR peptides, and showed specific reactivity in Western blotting with a high molecular weight protein produced by the LS174T colon carcinoma cell line. The use of shorter peptides indicated that the minimum peptide epitopes for these MAbs were different. Mab 3A2 reacted with amino acids 5-19 of the MUC2 VNTR by inhibition ELISA but not by direct ELISA, while 4F1 reacted with this peptide in both assays. Furthermore, 4F1 reacted in direct ELISA when a larger (29 amino acid) MUC2-derived peptide was coated onto the assay plate by incubating in carbonate buffer or by drying the peptide onto the assay plate, while 3A2 only reacted when this peptide was coated in carbonate buffer. The different specificity of the MAbs was also illustrated by the reactivity of 4F1 but not 3A2 with partially deglycosylated cystic fibrosis mucin. Immunohistochemical analysis with these MAbs revealed a strong reactivity with lung, gastric and colon tumours relative to normal tissue, with some breast and ovarian tumours also reacting. Both MAbs stained some normal goblet cells in the perinuclear region but not the mucin droplet or secreted mucin, indicating a reaction with immature (poorly glycosylated) mucin in the endoplasmic reticulum and/or golgi, but not with mature (fully glycosylated) mucin. In contrast, tumours showed strong diffuse cytoplasmic staining. 4F1 also showed weak apical cytoplasmic staining in some goblet cells and stained some tumours which showed no reactivity with 3A2. These antibodies should prove useful in the study of MUC2 structure and function, and in the diagnosis of some tumours.

Plasma testosterone (T) concentrations, measured in wild bats of P. poliocephalus in Queensland in 1983-87, showed a peak during the mating season in March. Plasma androstenedione (A) concentrations changed less dramatically with season. Mean testicular concentration and total content of T and A was substantially greater in March than in regressed testes in July-October. Paired adrenal glands were heavier during February to April than during September to November. In the same wild population, throughout a single breeding season (1987), plasma T concentrations were significantly higher in mid-March than 3 weeks previously or 3 weeks later. Testicular T content rose as the breeding season progressed, being greatest during March, coinciding with the large rise in plasma T concentrations. Testicular T concentration and content were correlated significantly with plasma T concentrations. Adrenal glands contained T, but the absolute concentrations were much lower than in the testis. No significant changes in plasma, testicular or adrenal A concentrations were found as the breeding season progressed. The large increase in plasma T during the mating season appears to be due to increased testicular production.

Adult male flying foxes Pteropus poliocephalus and P. scapulatus were captured in south-east Queensland and kept in outdoor enclosures. Testicular size (TS), plasma testosterone concentrations (PTC) and body weight (BW) were measured over 1-year periods. Testicular recrudescence in P. poliocephalus began before the summer solstice and TS was greatest during mid-March (autumn) and lowest from July to September. Large increases in PTC were observed in all individuals approximately 1 month after the peak in TS. BW also increased around the time of the mating season, changes being correlated significantly with changes in TS. Mating occurred between April and June, and births from late October to late November. In P. scapulatus, TS was greatest in the spring (October) and least in the autumn (February to May); PTC fluctuated throughout the year in this species but, unlike P. poliocephalus, did not show a single large increase in the mating season. BW showed a similar seasonal pattern to that seen in P. poliocephalus, being greatest at the time of greatest TS. Mating occurred in October to November, and births in autumn. In captivity, in outdoor enclosures, these species maintained the seasonal reproductive patterns observed in the wild. The 2 species respond differently to the same environmental cues in terms of regulation of the timing of their breeding seasons.

Microbiologic surveillance of both the patients and the ambient environment of a surgical intensive care unit allowed us to relate the incidence of nosocomial respiratory tract infection to levels of airborne bacteria. Over the study period respiratory tract nosocomial infection rates varied from 0.7% to 17.0%, and nonrespiratory infection rates varied from 1.0% to 25.0%. Airborne bacteria counts during that time varied from 1.0 +/- 0.8 S.E. CFU/ft3 to 96.0 +/- 6.8 S.E. CFU/ft3. There was a reasonably close correlation between airborne bacteria levels and the incidence of nosocomial pneumonia (r = 0.81, p less than 0.05). Furthermore, there was a close correlation between a specific organism nosocomial infection rate and the number of colonies of that organism present in the air (r = 0.88, p less than 0.05). In contrast, there was no significant relationship between airborne bacteria counts and nonrespiratory attack rates (r = 0.60, p less than 0.05). If the bacteria traveled from the air to the patients, there appear to be at least three possible explanations for this significant relationship: (1) direct inoculation of the airway by the airborne bacteria; (2) inoculation of the airway by direct contact, which is related to the degree of "cleanliness" of the environment; and (3) an increased incidence of contaminated respiratory equipment and airway inoculation because of high counts of airborne bacteria. It is also possible that high bacterial air counts represent contamination of the air from patients with respiratory infections. Regardless of the pathway(s), surveillance of the ambient environment may prove to be a useful epidemiologic tool in the study and control of nosocomial respiratory tract infections in certain high-risk patient care areas.

The frequency of handwashing in two intensive care units (ICUs) was observed. Handwashing after direct contact with patients or their support equipment was recorded. The ratio of beds to sinks was 1:1 in the medical ICU and 4:1 in the surgical ICU. Surveillance of physicians, nurses, and other personnel demonstrated a greater frequency of handwashing by nurses (63%) compared with physicians (19%) and other personnel (25%). The nurses in the unit with one sink per bed had a significantly greater number of handwashes (76%) than those in the unit with fewer sinks (51%).