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In this paper, traditional Hmong explanations about miscarriage and the ethnomedical knowledge and practices which pertain to it are explored. They are derived from in-depth interviews and participant observation with the Hmong who are now living in Melbourne, Australia. The loss of pregnancy creates considerable anxiety in Hmong society. This is not only because it calls for a socially justifiable explanation for a family's failure to extend their lineage, but also reduces the venue for a soul to be re-born into the family. This is a threat for Hmong society since it means the extinction of the family, clan and lineage and hence Hmong society. The cultural construction of the causes of miscarriage among the Hmong surrounds two main categories: the natural world which is related to the woman's body and her behaviour; and the supernatural world. These explanations point to the influence that individuals, both living and dead, have on pregnancies. In traditional Hmong society, health is perceived as a harmony between the social, and religious or supernatural realm. A woman being unable to bring forth an offspring because of miscarriage indicates disharmony with the living and/or between the living and the dead. [ABSTRACT FROM AUTHOR]

There are few population based studies which explore the views immigrant women have of the maternity care they receive in their new homelands. Three hundred and eighteen Vietnamese, Turkish and Filipino women who gave birth in three major city hospitals in Melbourne, Australia were interviewed about their experiences of maternity care. Outcomes and experiences for women with different levels of English fluency were studied, as were women's needs and preferences for assistance with interpreting. Observance of traditional cultural practices surrounding birth and the impact of not being able to observe such practices on women's experiences of care were also explored. Women in the study not fluent in English experienced problems in commununicating with their caregivers and these were reflected in less positive experiences of care. Women were less concerned that caregivers knew little about their cultural practices than they were about care they experienced as unkind, rushed, and unsupportive. Maternity care for immigrant women is only likely to improve when barriers to effective communication are addressed and attention is paid to raising standards of care. [ABSTRACT FROM AUTHOR]

In this paper we discuss the perceptions and experience of prenatal testing among 30 Thai women in Australia. Ethnographic interviews and participant observation were used to elicit information in the study. The results show that most Thai women have positive attitudes toward prenatal testing, particularly that of ultrasound scan. Women see prenatal testing as a means for reassurance about the health and well-being of their foetus, to detect the sex of their foetus, and to create excitement about life in their uterus. However, there are also women who have negative attitudes toward or are ambivalent about prenatal testing. Despite some doubts about prenatal testing, women fell that it offers some answers about the well-being of their foetus and hence in the end they accept it as part of their pregnancy. We also discuss explanations for the acceptance of prenatal testing among Thai women. [ABSTRACT FROM AUTHOR]

The sulfone derivative of the non-steroidal anti-inflammatory drug (NSAID), sulindac, has been reported to inhibit mammary and colon tumor formation in rodent models of chemically-induced carcinogenesis. Unlike its parent compound, this metabolite lacks cyclo-oxygenase inhibitory activity. A tumor induction protocol, consisting of NNK administration in the drinking water over several weeks to model chronic human exposure, was used to test whether the sulfone (called FGN-1) could inhibit the formation of primary lung tumors in mice. A total of 150 female, AIN-76A-fed, A/J mice received 9 mg of NNK each. Concentrations of FGN-1 that had been previously determined not to affect body weight gain were added to the food at levels of 0, 250, 500 and 750 mg/kg of diet (30 mice/group) starting 2 weeks before NNK administration and continuing for 22 weeks. At that time pleural surface tumors were counted. Tumor incidence decreased significantly from 96% in the control diet and 93% in the 250 FGN-1 mg/kg diet to 63 and 67% in the 500 and 750 mg FGN-1/kg diet groups, respectively (P < 0.001 by chi-square analysis). Lung tumor multiplicity decreased from 18.1 ± 3 tumors/mouse (mean ± SEM, control diet) to 12.3 ± 3 (250), 5.3 ± 1 (500) and 2.1 ± 1 (750) (P < 0.0005 by post hoc ANOVA). In previous studies using this carcinogenesis protocol, the maximum tolerated dose of sulindac inhibited lung tumor multiplicity by no more than 50% with no effect on incidence. This dose-dependent reduction in tumorigenesis by a non-toxic dose of FGN-1 indicates a strong chemopreventive activity against experimental induction of lung carcinogenesis. The greater potency of the sulfone over sulindac and its lack of toxic side effects because of its inability to affect cyclo-oxygenase activity suggests that clinical testing in individuals at high risk for lung cancer should be considered. [ABSTRACT FROM PUBLISHER]

Purpose: Project Building Bridges was funded by the U.S. Department of Education Office of Special Education Programs to address the shortage of speech-language pathologists qualified to serve students with complex communication needs who benefit from augmentative and alternative communication (AAC) and are culturally and linguistically diverse. The purpose was to train future speech-language pathologists in culturally responsive AAC practices through coursework and fieldwork in AAC integrated into the Master of Science degree in Speech, Language and Hearing Sciences., Method: Fifty-seven graduate students completed the project. The scholars' curriculum consisted of two AAC courses, both on-campus and externship AAC clinical practicum experiences to provide services to multicultural and linguistically diverse students, a U.S. or international service-learning opportunity, and cumulative portfolio presentations., Results: Mixed-methods outcome measures consisted of four sets of pre- and postsurveys and qualitative feedback from exit interviews to assess changes in graduate student competencies. Significant differences were demonstrated between scholars' pre- and post-assessments of confidence ratings. Significant differences were also demonstrated in both scholars' and school mentors' pre- and post-assessments of competency ratings. No significant differences were found between evaluations of AAC preparation by Clinical Fellowship (CF) candidates and their CF mentors at 1 year postgraduation., Conclusions: Project Building Bridges provides a framework for preparing highly qualified speech-language pathologists to serve culturally and linguistically diverse students who benefit from AAC as evidenced by pre- and postsurvey results. The project can serve as a model for other university programs in the development of preservice preparation programs focusing on culturally and linguistically diverse students with AAC needs.

Introduction: Obesity is associated with increased risk of hypercapnic respiratory failure, prolonged duration on mechanical ventilation, and extended weaning periods., Objective: Pilot study to determine whether morbidly obese adult tracheotomized subjects (body mass index [BMI] ⩾ 40) can be more efficiently weaned from the ventilator by optimizing their positive end-expiratory pressure (PEEP) using either an esophageal balloon or the best achieved static effective compliance., Methods: We randomly assigned 25 morbidly obese adult tracheotomized subjects (median [interquartile range] BMI 53.4 [26.4]; range 40.4-113.8) to 1 of 2 methods of setting PEEP; using either titration guided by esophageal balloon to overcome negative transpulmonary pressure (Ptp) (goal Ptp 0-5 cmH 2 O) (ESO group) or titration to maximize static effective lung compliance (Cstat group). Our outcomes of interest were number of subjects weaned by day 30 and time to wean., Results: At day 30, there was no significant difference in percentage of subjects weaned. 8/13 subjects (62%) in the ESO Group were weaned vs. 9/12(75%) in the Cstat Group ( P  = 0.67). Among the 17 subjects who weaned, median time to ventilator liberation was significantly shorter in the ESO group: 3.5 days vs Cstat group 14 days ( P  = .01). Optimal PEEP in the ESO and Cstat groups was similar (ESO mean ± SD = 26.5 ± 5.7 cmH 2 O and Cstat 24.2 ± 7 cmH 2 O ( P  = .38)., Conclusions: Optimization of PEEP using esophageal balloon to achieve positive transpulmonary pressure did not change the proportion of patients weaned. Among patients who weaned, use of the esophageal balloon resulted in faster liberation from mechanical ventilation. There were no adverse consequences of the high PEEP (mean 25.4; range 13-37 cmH 2 O) used in our study. The study was approved by the Institutional Review Board at our institution (UMCIRB#10-0343) and registered with clinicaltrials.gov (NCT02323009)., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Inflammatory oncotaxis, the phenomenon in which mechanically injured tissues are predisposed to cancer metastases, has been reported for a number of tumor types, but not previously for histologically proven lung cancer. We review clinical and experimental evidence and mechanisms that may underlie inflammatory oncotaxis, and provide illustrative examples of two patients with squamous cell carcinoma of the lung who developed distant, localized metastatic disease at sites of recent physical trauma. Trauma may predispose to metastasis through two distinct, but not mutually exclusive, mechanisms: (1) physical trauma induces tissue damage and local inflammation, creating a favorable environment that is permissive for seeding of metastatic cells from distant sites; and/or (2) micrometastatic foci are already present at the time of physical injury, and trauma initiates changes in the microenvironment that stimulate the proliferation of the metastatic cells. Further exploration of post-traumatic inflammatory oncotaxis may elucidate fundamental mechanisms of metastasis and could provide novel strategies to prevent cancer metastasis.

The inflammatory cytokines tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) stimulate production of the inflammatory mediators prostaglandin E₂ (PGEγ), prostacyclin (PGIγ), and nitric oxide (NO) in cultured lung epithelial cells. Pretreatment of these cells with the selective MEK1/2 (mitogen-activated protein kinase/extracellular signal-regulated kinase [ERK] kinase 1/2) inhibitor U0126 blocked ERK1/2 activation and inhibited cytokine-induced production of these inflammatory mediators. Primary bronchiolar epithelial Clara cells treated with TNFα and IFNγ also produced increased PGE₂, PGI₂, and NO, and PG and NO production was decreased by MEK inhibition. U0126 differentially affected cyclooxygenase (COX)-1, COX-2, and inducible NO synthase (iNOS) expression in cell lines, however, suggesting that MEK1/2 regulates prostanoid and NO production by means other than inducing their biosynthetic enzymes. Functionally, inhibition of MEK1/2 caused G1 cell cycle arrest and decreased cyclin D1 expression, but these effects were not related to decreased prostanoid production. These results indicate separate proinflammatory and proliferative roles for ERK1/2 in lung epithelial cells. During lung tumor formation in vivo, ERK1/2 phosphorylation increased as lung tumors progressed. Since tumor-derived cells were more sensitive than nontumorigenic cells to the antiproliferative effects of U0126, MEK1/2 inhibition may serve as an attractive chemotherapeutic target.

Tumor-associated macrophages (TAMs) encourage and coordinate neoplastic growth. In late stage human lung adenocarcinoma, TAMs exhibited mixed M1 (classical; argI(low)iNOS(high)) and M2 (alternative; argI(high)iNOS(low)) polarization based on arginine metabolism. In several murine cancer models including chemically and genetically-induced primary lung tumors, prostate tumors, colon xenografts, and lung metastases, TAMs expressed argI(high)iNOS(low) early during tumor formation; argI(low)iNOS(high) polarization also occurred during malignancy in some models. In a chemically-induced lung tumor model, macrophages expressed argI(high)iNOS(low) within one week after carcinogen treatment, followed by similar polarization of bone marrow-derived monocytes (BDMCs) a few days later. TAMs surrounding murine prostate tumors also expressed argI(high)iNOS(low) early during tumorigenesis, indicating that this polarization is not unique to neoplastic lungs. In a human colon cancer xenograft model, the primary tumor was surrounded by argI(high)iNOS(low)-expressing TAMs, and BDMCs also expressed argI(high)iNOS(low), but pulmonary macrophages adopted argI(high)iNOS(low) polarization only after tumors metastasized to the lungs. Persistence of tumors is required to maintain TAM polarization. Indeed, in both conditional mutant Kras- and FGF10-driven models of lung cancer, mice expressing the transgene develop lung tumors that regress rapidly when the transgene is silenced. Furthermore, pulmonary macrophages expressed argI(high)iNOS(low) on tumor induction, but then returned to argI(low) iNOS(low) (no polarization) after tumors regressed. Manipulating TAM function or depleting TAMs may provide novel therapeutic strategies for preventing and treating many types of cancer.

The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. In response to ligand, EGFR is internalized and degraded by the ubiquitin-proteasome/lysosome pathway. We previously reported that metabolites of the nonsteroidal anti-inflammatory drug sulindac downregulate the expression of EGFR and inhibit basal and EGF-induced EGFR signaling through extracellular signal-regulated kinase 1/2. We now have evaluated the mechanisms of sulindac metabolite-induced downregulation of EGFR. EGF-induced downregulation of EGFR occurs within 10 minutes and lasts for 24 hours. By contrast, downregulation of EGFR by sulindac sulfide and sulindac sulfone was first evident at 4 and 24 hours, respectively, with maximal downregulation at 72 hours. Pretreatment with either the lysosomal inhibitor chloroquine or the proteosomal inhibitor MG132 blocked sulindac metabolite-induced downregulation of EGFR. Sulindac metabolites also increased the ubiquitination of EGFR. Whereas sulindac metabolites inhibited phosphorylation of EGFR pY1068, they increased phosphorylation of EGFR pY1045, the docking site where c-Cbl binds, thereby enabling receptor ubiquitination and degradation. Immunofluorescence analysis of EGF and EGFR distribution confirmed the biochemical observations that sulindac metabolites alter EGFR localization and EGFR internalization in a manner similar to that seen with EGF treatment. Expression of ErbB family members HER2 and HER3 was also downregulated by sulindac metabolites. We conclude that downregulation of EGFR expression by sulindac metabolites is mediated via lysosomal and proteosomal degradation that may be due to drug-induced phosphorylation at pY1045 with resultant ubiquitination of EGFR. Thus, sulindac metabolite-induced downregulation of EGFR seems to be mediated through mechanism(s) similar, at least in part, to those involved in EGF-induced downregulation of EGFR., ((c) 2010 AACR.)

Objective: TraumaSCAN-Web (TSW) is a computerized decision support system for assessing chest and abdominal penetrating trauma which utilizes 3D geometric reasoning and a Bayesian network with subjective probabilities obtained from an expert. The goal of the present study is to determine whether a trauma risk prediction approach using a Bayesian network with a predefined structure and probabilities learned from penetrating trauma data is comparable in diagnostic accuracy to TSW., Methods: Parameters for two Bayesian networks with expert-defined structures were learned from 637 gunshot and stab wound cases from three hospitals, and diagnostic accuracy was assessed using 10-fold cross-validation. The first network included information on external wound locations, while the second network did not. Diagnostic accuracy of learned networks was compared to that of TSW on 194 previously evaluated cases., Results: For 23 of the 24 conditions modeled by TraumaSCAN-Web, 16 conditions had Areas Under the ROC Curve (AUCs) greater than 0.90 while 21 conditions had AUCs greater than 0.75 for the first network. For the second network, 16 and 20 conditions had AUCs greater than 0.90 and 0.75, respectively. AUC results for learned networks on 194 previously evaluated cases were better than or equal to AUC results for TSW for all diagnoses evaluated except diaphragm and heart injuries., Conclusions: For 23 of the 24 penetrating trauma conditions studied, a trauma diagnosis approach using Bayesian networks with predefined structure and probabilities learned from penetrating trauma data was better than or equal in diagnostic accuracy to TSW. In many cases, information on wound location in the first network did not significantly add to predictive accuracy. The study suggests that a decision support approach that uses parameter-learned Bayesian networks may be sufficient for assessing some penetrating trauma conditions.

Pelvic fractures are associated with significant morbidity and mortality. Despite advances in emergency, radiologic, surgical, and ICU care that have improved survival during the past decade, the morbidity and the mortality remain significantly high. This article focuses on the recent developments in the initial management of pelvic fractures including the use of external pelvic binders, radiographic imaging, interventional radiology, and extraperitoneal packing.

Background: High-speed police pursuits are common in the United States (US). Most states do not gather statistics on police pursuits, pursuit crashes, injuries or fatalities for annual review., Objective: The objective of this study is to determine the number of pursuit fatalities to officers, those in the chased vehicle, and those uninvolved in pursuits from 1982-2004., Methods: A review of police pursuit fatalities reported to the National Highway Traffic Safety Administration (NHTSA) Fatality Analysis Reporting System (FARS) database from 1982-2004. The data was reviewed for fatalities, demographic data, alcohol involvement, road surface type (rural versus urban) and mechanism of collision leading to a pursuit fatality., Results: From 1982-2004, 881,733 fatal crashes were reported to NHTSA, leading to 987,523 fatalities. Of fatal crashes, 6,336 (0.7%) were secondary to pursuits, leading to 7,430 (0.8%) fatalities, a mean of 323 per year. Among these fatalities, chased vehicle occupants accounted for 5,355 (72%); police for 81 (1%); those uninvolved for 1994 (27%). Of fatalities, 6074 (82%) were male, 2,092 (28%) were children and adolescents. Mean age of death was 24 years. African-Americans 1,154 (24%) and Native Americans 101 (2%) died at a higher proportion than their percentage of the US population. Collisions with solid objects accounted for 3,175 (59%) of fatalities in the chased vehicles. Collisions with other moving vehicles accounted for 1,434 (80%) of fatalities of vehicular occupants uninvolved in pursuits. Most fatal crashes, 3,130 (62%), occurred on urban roadways. Alcohol was involved in 4,628 (62%) fatalities. Of police fatalities, 20 (25%) were intoxicated., Conclusions: Police pursuits results in a small yet significant number of fatal motor vehicular crashes and fatalities. All states should record the total number of police pursuits, pursuit crashes, injuries and fatalities for annual review. The findings in this study have important operational implications for EMS care.

Colorectal cancer is the second leading cause of cancer mortality in the United States. Substantial human and animal data support the ability of nonsteroidal anti-inflammatory drugs to cause regression of existing colon tumors and prevent new tumor formation. The mechanism by which the nonsteroidal anti-inflammatory drug sulindac prevents tumor growth is poorly understood and seems complex as sulindac can modulate several growth-related signaling pathways. Sulindac metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate cyclic GMP-dependent protein kinase (PKG); (b) activate c-jun NH2-terminal kinase (JNK); (c) inhibit extracellular signal-regulated kinase 1/2 (ERK1/2); and (d) decrease beta-catenin protein expression at times and doses consistent with apoptosis. The purpose of this study was to determine if PKG, ERK1/2, JNK, and beta-catenin are independent targets for sulindac in vitro. Pharmacologic activation of PKG with YC-1 increases JNK phosphorylation and induces apoptosis in colon cancer cells without modulating ERK1/2 phosphorylation or beta-catenin protein expression. Inhibition of ERK1/2 with U0126 induces apoptosis but fails to activate JNK phosphorylation or down-regulate beta-catenin protein expression. Cotreatment with U0126 and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, JNK, and beta-catenin. These results indicate that sulindac metabolites modulate ERK1/2 and PKG pathways independently in colon cancer cells and suggest that the full apoptotic effect of sulindac is mediated by more than one pathway. Using similar combinatorial approaches in vivo may provide more effective, less toxic chemopreventive and chemotherapeutic strategies. Such therapies could dramatically reduce the incidence and death rate from colorectal cancer.

Background: Terrorist bombings remain a significant threat in the United States. However, minimal longitudinal data exists regarding the medical and public health impact because of bombings., Methods: We conducted a retrospective analysis of the number of incidents, injuries, and deaths because of explosive, incendiary, premature, and attempted bombings from January 1983 to December 2002. Morbidity and mortality by motives, target locations, and materials used were evaluated., Results: In the United States, 36,110 bombing incidents, 5,931 injuries, and 699 deaths were reported. There were 21,237 (58.8%) explosive bombings, 6,185 (17.1%) incendiary bombings, 1,107 (3.1%) premature bombings, and 7,581 (21.0%) attempted bombings. For explosive bombings with known motives, 72.9% of injuries and 73.8% of deaths were because of homicide. For incendiary bombings with known motives, 68.2% of injuries were because of extortion and revenge, and 53.5% of deaths were due to homicide. Private residences accounted for 29.0% of incidents, 31.5% of injuries, and 55.5% of deaths. Government installations accounted for 4.4% of incidents but were the site of 12.7% of injuries and 25.5% of deaths. In bombings with known materials, nitrate-based fertilizers accounted for 36.2% of injuries and 30.4% of deaths, and smokeless powder and black powder accounted for 33.2% of injuries and 27.1% of deaths., Conclusions: Illegal bombings and related injuries commonly occur in the United States. Because of the easy availability of bombing materials, government agencies and healthcare providers should prepare for potential mass-casualty bombings.

Background: Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased mortality from colorectal cancer (CRC). NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2) signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF) receptor (EGFR)., Methods: HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068), total EGFR, phosphorylated ERK1/2 (pERK1/2), total ERK1/2, activated caspase-3, and alpha-tubulin., Results: EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation., Conclusion: These results suggest that downregulation of EGFR signaling by sulindac metabolites may occur, at least in part, by inhibiting activation and expression of EGFR. Inhibition of EGFR signaling may account for part of the growth inhibitory and chemopreventive effects of these compounds.

Objective: To evaluate the discriminatory power of TraumaSCAN-Web, a system for assessing penetrating trauma, using retrospective multi-center case data for gunshot and stab wounds to the thorax and abdomen., Methods: 80 gunshot and 114 stab cases were evaluated using TraumaSCAN-Web. Areas under the Receiver Operator Characteristic Curves (AUC) were calculated for each condition modeled in TraumaSCAN-Web., Results: Of the 23 conditions modeled by TraumaSCAN-Web, 19 were present in either the gunshot or stab case data. The gunshot AUCs ranged from 0.519 (pericardial tamponade) to 0.975 (right renal injury). The stab AUCs ranged from 0.701 (intestinal injury) to 1.000 (tracheal injury).

Nonsteroidal anti-inflammatory drugs (NSAIDs) including sulindac have shown potent chemopreventive and tumor regressive effects against colorectal cancer, the second leading cause of cancer death in the United States. However, the mechanisms by which sulindac inhibits tumor cell growth are not completely understood. We previously reported that sulindac metabolites inhibit the mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling cascade in colorectal cancer cell lines at doses that induce apoptosis, and inhibition of MEK/ERK activity with U0126 is sufficient to induce apoptotic cell death. To determine whether inhibition of MEK/ERK activity is necessary for sulindac-induced apoptosis of human colon cancer cells, stable transfectants were created that express an activated MEK1 gene in HT29 cells. HT29-MEK1(R4F) clones displayed a 10- to 20-fold increase in MEK1 activity compared with control HT29-pCEP4 clones. When compared with control HT29-pCEP4 clones, HT29-MEK1(R4F) clones were resistant to both apoptosis and inhibition of ERK1/2 phosphorylation induced by sulindac metabolites. These results suggest that inhibition of MEK/ERK signaling is necessary for the induction of apoptosis by sulindac metabolites.

Colorectal cancer (CRC) is the second leading cause of cancer death in the USA. Accumulation of beta-catenin protein is nearly ubiquitous in colon adenomas and cancers, presumably due to mutations in the APC or beta-catenin genes that inhibit proteasome-dependent degradation of beta-catenin protein. Substantial clinical, epidemiological, and animal evidence indicate that sulindac and other non-steroidal anti-inflammatory drugs (NSAIDs) prevent the development of CRC. The mechanisms by which sulindac exerts its potent growth inhibitory effects against colon tumor cells are incompletely understood, but down-regulation of beta-catenin has been suggested as one potential mechanism. The goal of this study was to determine the mechanism of beta-catenin protein down-regulation by sulindac metabolites. Treatment of human colon cancer cell lines with apoptotic concentrations of sulindac metabolites (sulindac sulfide, sulindac sulfone) induced a dose- and time-dependent inhibition of beta-catenin protein expression. Inhibition of proteasome activity with MG-132 partially blocked the ability of sulindac sulfide and sulindac sulfone to inhibit beta-catenin protein expression. Pretreatment with the caspase inhibitor z-VAD-fmk blocked morphological signs of apoptosis as well as caspase cleavage, and also partially prevented beta-catenin degradation by sulindac metabolites. These effects occurred in cells with bi-allelic APC mutation (SW480), with wild-type APC but mono-allelic beta-catenin mutation (HCT116) and in cells that lack expression of either COX-1 or -2 (HCT15). These results indicate that loss of beta-catenin protein induced by sulindac metabolites is COX independent and at least partially due to reactivation of beta-catenin proteasome degradation and partially a result of caspase activation during the process of apoptosis.

Colorectal cancer is the second leading cause of cancer death in the United States. Nonsteroidal anti-inflammatory drugs including sulindac are promising chemopreventive agents for colorectal cancer. Sulindac and selective cyclooxygenase (COX)-2 inhibitors cause regression of colonic polyps in familial polyposis patients. Sulindac induces apoptotic cell death in cancer cells in vitro and in vivo. In tumor cells, activation of extracellular-regulated kinase (ERK) 1/2 results in phosphorylation of several ERK1/2 effectors, including the proapoptotic protein Bad. Phosphorylation of Ser112 by ERK1/2 inactivates Bad and protects the tumor cell from apoptosis. Sulindac metabolites and other nonsteroidal anti-inflammatory drugs selectively inhibit ERK1/2 phosphorylation in human colon cancer cells. In this study we show that epidermal growth factor (EGF) strongly induces phosphorylation of ERK1/2 and Bad in HT29 colon cancer cells. EGF-stimulated phosphorylation of ERK and Bad is blocked by pretreatment with U0126, a selective MAP kinase kinase (MKK)1/2 inhibitor. Similarly, pretreatment with sulindac sulfide blocks the ability of EGF to induce ERK1/2 and Bad phosphorylation, but also down-regulates total Bad but not ERK1/2 protein levels. The ability of sulindac to block ERK1/2 signaling by the EGF receptor may account for at least part of its potent growth-inhibitory effects against cancer cells.

Forty percent of pregnant women aged 37 years and over do not have prenatal diagnosis despite being eligible for a free test. The present study aimed to determine how often, and which, untested women were making a choice about this, how many declined an offer and why. A questionnaire was given to untested women, aged 37 years and over, at no less than 24 weeks gestation. A total of 375 (81.5%) women declined, 72 (16%) were not offered a test and 13 presented too late antenatally. There was a three-fold increased likelihood (OR 3.10 95% CI 1.44, 6.65) of no offer for urban non-English speaking background women, compared with the reference group (metropolitan, English speaking). Unpartnered women were also significantly less likely to receive an offer (OR 3.18, 95% CI 1.19, 8.46). Risk to the baby was the main reason for declining. When offered non-invasive prenatal screening, most decliners of prenatal diagnosis accepted, even those who declined because they were opposed to abortion. We estimate that overall 33% of older pregnant women were being offered and declining amniocentesis and/or chorion villus sampling (CVS). Only 6% were not offered a test, but this small proportion is over-represented by minority groups who must be given equal opportunity to make this choice., (Copyright 2001 John Wiley & Sons, Ltd.)

Elevations in cyclin D1 content increase the phosphorylation status of retinoblastoma (Rb) protein to encourage cell cycle transit. We sought to determine if cyclin D1 content could be used as an index of cell proliferation in mouse lung epithelia following growth manipulations in vitro and in vivo. Rb protein concentration was high in 82-132 and LM2, two fast-growing neoplastic mouse lung epithelial cell lines. The hyperphosphorylated form of Rb predominated in these two cell lines, while Rb in slower-growing cell lines was predominantly hypophosphorylated. Consistent with this, more cyclin D1 protein was expressed in the fast-growing cell lines than in slower-growing cells. We therefore tested whether cyclin D1 content varied with growth status. The amount of cyclin D1 decreased upon serum removal coincident with growth inhibition and then increased upon serum re-addition which stimulated resumption of proliferation. This correlation between cyclin D1 content and growth status also occurred in vivo. Cyclin D1 content increased when lungs underwent compensatory hyperplasia following damage caused by butylated hydroxytoluene administration to mice and in lung tumor extracts as compared with extracts prepared from uninvolved tissue or control lungs. We conclude that elevated cyclin D1 levels account, at least in part, for the hyperphosphorylation of Rb in neoplastic lung cells, and are associated with enhanced lung growth in vitro and in vivo.

Objective: to examine the perceptions and experience of breast-feeding practices among Thai women who are now living in Australia., Design: ethnographic interviews and participant observation among Thai women in Australia., Setting: Melbourne Metropolitan Area,Victoria, Australia., Findings: Thai women see breast milk as the most valuable food for newborn babies and young children. Breast milk is seen as 'human milk', while infant formula is referred to as 'animal milk'. Breast feeding is seen as beneficial not only to babies' health, but also to the mother's health. Women consume certain foods such as drinking hot water and consuming hot soup during the confinement period as a way to ensure breast milk production. Women appear to know that 'breast is best', but some lack accurate knowledge about breast feeding. They also receive inaccurate information regarding feeding practices from health professionals., Implications for Practice: there is no doubt that Thai women see that 'breast is best', therefore, the main message for those involved in giving breast-feeding advice is to 'make it easy for women to do it'. Only then can health services and care be made more meaningful to the many women who have decided to breast feed their babies in their new country.

Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac is associated with a decreased mortality from colorectal cancer. Sulindac causes regression of precancerous adenomatous polyps and inhibits the growth of cultured colon cell lines. Whereas induction of apoptotic cell death is thought to account for the growth inhibitory effect of sulindac, less is known about its biochemical mechanism(s) of action. Sulindac is metabolized in vivo to sulfide and sulfone derivatives. Both the sulfide and sulfone metabolites of sulindac as well as more potent cyclic GMP-dependent phosphodiesterase inhibitors were shown to cause inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation at doses (40-600 microM) and times (1-5 days) consistent with the induction of apoptosis by the drugs. Treatment of HCT116 human colon cancer cells with the specific mitogen-activated protein kinase kinase, U0126 (5-50 microM) resulted in a time- and dose-dependent inhibition of ERK1/2 phosphorylation, and induction of apoptosis. U0126 treatment (20 microM) increased basal apoptosis, and potentiated the apoptotic effect of sulindac sulfide and sulindac sulfone. These results suggest that the inhibition of ERK1/2 phosphorylation is responsible for at least part of the induction of programmed cell death by sulindac metabolites. Inhibition of ERK1/2 activity may, therefore, be a useful biochemical target for the development of chemopreventive and chemotherapeutic drugs for human colon cancer.

In this paper, I discuss childrearing beliefs and practices in Hmong culture. In particular I focus on issues related to souls and ceremonies for a newborn infant in Hmong society. The Hmong believe that each living body has three souls. For a newborn infant, the first soul enters his or her body when he or she is conceived in the mother's womb. The second soul enters when the baby has just emerged from the mother's body and taken its first breath. The third soul, however, will have to be called on the third morning after birth, as will be discussed in this paper. If all three souls are secured in the infant's body, he or she will be healthy and hence thrive well. On the contrary, the infant may become ill and eventually die if all three souls do not reside in his or her body. This, therefore, makes a soul calling ceremony on the third morning after birth essential in Hmong culture. I will show that for Hmong society to survive, the Hmong strongly adhere to their cultural beliefs and practices related to a newborn infant. These beliefs and practices tie the Hmong with not only their family and their society at large, but also the supernatural world.

Objective: To examine traditional and changed beliefs and practices related to the puerperium of Hmong women in Melbourne, Australia., Design: An ethnographic study of reproductive health among Hmong women in Australia., Setting: Melbourne Metropolitan Area, Victoria, Australia., Participants: 27 Hmong women, three shamans, two medicine women and one magic healer who are now living in Melbourne., Findings: In the Hmong tradition, the first 30 days after birth is seen as the most dangerous period for a new mother. There are several beliefs and practices which women must observe in order to regain strength and avoid poor health in the future. Lying near the fire in the first three days is one such belief. The woman's body during the puerperium is considered polluted. Hence, there are several rules to restrict the woman and the substance of her body. It appears the Hmong continue to observe their post-birth confinement practices regardless of their new environment. Most women mentioned that this is to avoid ill health and misfortune in the future. There are only a few customs which they have to modify due to changes in their living situations in a new country., Implications for Practice: Hmong cultural beliefs and practices concerning the puerperium in particular, and childbearing in general, have specific implications for midwifery care. Since midwives will continue to encounter many traditional beliefs and practices of the Hmong when providing birthing care to Hmong women, it is essential that their cultural beliefs and practices be taken into account. This will not only help to avoid misunderstanding, but also result in culturally appropriate and sensitive care for immigrant women.

This study attempts to understand the Vietnamese-Australian grandparenthood and their changing roles and psychological well-being. Using a qualitative approach, thirty-six grandparents participated in four focus group interviews. The findings reveal that Vietnamese grandparents play many important roles such as those of living ancestor, family historian, role model, teacher, mentor, nurturer, crony and mediator although at a reasonably modest level. Through assisting the parents, it creates a vital bridge between grandparents and grandchildren. Grandparents' most important roles are the maintenance of good emotional relationships and support, and the construction of harmony and continuity in their modified extended families. To be able to assume these roles grandparents need to actively explore and accept new values and to adapt values to new cultural context. A successful grandparenthood brings happiness to the family and this in turn positively influences grandparents' life satisfaction and psychological well-being and enhances their quality of life.

Objective: To describe the dilemmas for cross-cultural research in translating study instruments and implementing quality assurance methods, drawing on strategies utilised in the Mothers in a New Country (MINC) Study., Method: To translation of study instruments in the MINC Study included: forward and back translations, a bilingual group review process, consultation with bilingual content experts, piloting of different versions of translations, a process for exploring unresolved difficulties and caution in interpreting unusual study findings. Interview quality was assessed by: 1. An ongoing review of interviewer-prepared English coding schedules to ensure completeness of data and identify problems with interview administration. 2. Analysis of fully translated transcripts of six randomly selected early interviews to assess the accuracy and consistency with which questions were asked. 3. A comparison of data sources for 45 randomly selected interviews (original language interview schedules, English coding schedules and translated interview transcripts) to determine the rate and nature of discrepancies., Results: Translation strategies that went beyond simple forward and back translations achieved more reliable and appropriate translations. The complexity of language and cultural differences sometimes still meant less than satisfactory results. Interview tapes played an important quality assurance role, enabling feedback to the interviewers and providing a basis of comparison for identification of data discrepancies., Implications: Ensuring good data quality in cross-cultural research is both critically important and difficult. Open discussion of the problems and concerted efforts to deal with them would benefit future research.

Objective: To discuss a range of strategies to address the methodological and practical challenges in designing cross-cultural public health studies., Method: The Mothers in a New Country (MINC) Study was an interview study of 318 Vietnamese, Turkish and Filipino recent mothers exploring their views of maternity care and the early months of motherhood. It was carried out in Melbourne between 1994 and 1997. Sampling, recruitment, retention and representativeness all pose problems for studies involving non-English-speaking background immigrant populations, as do selection, training and support processes for bicultural interviewers. These issues are discussed with reference to the strategies undertaken to tackle them in the MINC Study., Results: In the MINC Study, a systematic approach to sampling and recruitment, combined with a flexible and sensitive study protocol were largely successful both in achieving in adequate sample size and a largely representative study sample. Similarly, paying significant attention to the selection, training and ongoing support of the biocultural interviewers employed on the study contributed greatly to its successful completion and enhanced confidence in the study findings., Implications: Both researchers and funders need to take seriously the implications of the many methodological and practical issues involved in designing sound cross-cultural public health studies. In particular, there are major implications for study costs and timelines. However, the benefits to be gained are significant.

The roles of growth factors in mouse lung neoplasia were investigated by examining receptors for platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) in epithelial cell lines. Whereas nontumorigenic lung cells expressed mRNA and protein for PDGF receptor (PDGFR)-alpha, PDGFR-beta, and EGF receptor (EGFR), five of six neoplastic lines did not. Because this exceptional tumorigenic cell line grows slowly, we hypothesized that receptor levels increased with cell stasis. To test this hypothesis, serum concentrations were manipulated, and log-phase and post-confluent cells were compared. Consistent with our hypothesis, PDGFR-alpha and EGFR contents, but not PDGFR-beta contents, increased at stasis. Ki-ras mutation initiates lung tumorigenesis in mice, but activation of Ki-ras did not affect receptor expression. This was determined both by transfecting nontumorigenic cells with activated Ki-ras and neoplastic cells with a Ki-ras antisense construct and by diminishing Ki-ras activation by using a farnesyltransferase inhibitor. Stasis-associated upregulation of growth-factor receptor expression suggests a function in lung cell differentiation that is abrogated during neoplastic growth.

Objective: To describe the experience of postpartum care among Thai women in Melbourne, Australia., Design: Ethnographic interviews and participant observation with women in relation to postpartum care and practices., Setting: Melbourne Metropolitan Area, Victoria, Australia., Participants: 26 Thai born women who gave birth in Australia., Findings: The Thai women had varying views about the length of time they should spend in hospital and the care they received. Ten of the twelve women who had had a caesarean birth stayed in hospital for six or more days, consistent with the hospital practice. However, most of those who had had a vaginal delivery opted to go home earlier than the standard hospital practice of four days stay. This was because they were unhappy about specific hospital practices, the hospital environment, or because there are several Thai confinement customs, which, traditionally, a new mother must observe in order to maintain good health and avoid future ill health and which they were not able to follow in hospital. Nevertheless, most women were satisfied with their postpartum care. Most women were aware of the Thai cultural beliefs and practices. However, they showed varying ways of coping with the hospital environment in relation to their varying social situations., Implications for Practice: Thai women are diverse in their needs, perceptions and experience of postpartum care. Therefore, it is appropriate neither to stereotype all Thai women as requiring to follow traditional confinement practices nor to require them to adjust to standard hospital practices. Rather an environment of caring concern whereby each woman's individual needs can be solicited, understood and, where possible, attended to as required. The challenge is in achieving this.

Objective: To assess Filipino, Turkish and Vietnamese women's views about their care during the postnatal hospital stay., Design: Interviews were conducted with recent mothers in the language of the women's choice, 6-9 months after birth, by three bilingual interviewers., Participants: Three hundred and eighteen women born in the Philippines (107), Turkey (107) and Vietnam (104) who had migrated to Australia., Setting: Women were recruited from the postnatal wards of three maternity teaching hospitals in Melbourne, Australia, and interviewed at home., Findings: Overall satisfaction with care was low, and one in three women left hospital feeling that they required more support and assistance with both baby care and their own personal needs. The method of baby feeding varied between the groups, with women giving some insight into the reason for their choice. A significant minority wanted more help with feeding, irrespective of the method. The need for rest was a recurrent theme, with women stating that staff's attitudes to individual preferences, coupled with lack of assistance, made this difficult. The majority of comments women made regarding their postnatal stay focused on the attitude and behaviour of staff and about routine aspects of care. Issues related to culture and cultural practices were not of primary concern to women., Conclusion: Maternity services need to consider ways in which care can focus on the individual needs and preferences of women.

This paper discusses the perceptions and experience of immigrant Thai women who have had a Caesarean or vaginal birth. The ethnographic study showed that there was a considerably high number of emergency Caesarean births among Thai mothers. All women, except one, had prepared for a vaginal birth. However, most had to accept an emergency Caesarean and were told of the birth process just before the birth had taken place. Many women were, therefore, not well prepared for the birth. Most women preferred a vaginal birth over Caesarean birth. However, some believed that Caesarean was a safe method of birth because of the benefits of medical technology. This paper also examines some explanations for a high incidence of emergency Caesarean among Thai women in this study.

Objective: To identify the perceptions and experience of pregnancy care, labour and birth of Thai women in Melbourne, Australia., Design: An ethnographic interview and participant observation with women in relation to pregnancy, labour and birth., Setting: Melbourne Metropolitan Area, Victoria, Australia., Participants: 30 Thai women who are now living in Melbourne., Findings: Thai women saw antenatal care as an important aspect of their pregnancy and sought care as soon as they suspected they were pregnant. They were more concerned about the well-being of their babies than their own health, therefore they attended all antenatal appointments. In general, these women were satisfied with care during labour, but some also had negative experiences with their caregivers and hospital routine. When asked to compare maternity services between Thailand and Australia, most of the women believed that services in Australia were better. However, women who had had good experiences of childbirth in Thailand, tended to have negative feelings about the Australian experience. There was also evidence in this study that most of these Thai women did not receive adequate information about care., Implications for Practice: Women's perceptions and experiences of antenatal care, labour and birth deserve attention, if appropriate and sensitive care is to be provided to women in Australia and elsewhere. It is only when women's voices are heard in all aspects of health-care delivery that we may see better and appropriate health services for women in childbirth.

Objectives: To compare the views of women from non-English-speaking backgrounds who received antenatal care at a public hospital clinic with those whose care was shared between a public hospital clinic and a general practitioner., Design: Structured interviews in the language of the woman's choice., Setting: Women were recruited from the postnatal wards of three maternity teaching hospitals in Melbourne between July 1994 and November 1995, and interviewed six to nine months later., Participants: Women born in Vietnam, Turkey and the Philippines who gave birth to a live healthy baby (over 1500 g) were eligible. Of 435 women recruited, 318 (Vietnamese [32.7%], Filipino [33.6%] and Turkish [33.6%]) completed the study., Main Outcome Measures: Women's ratings of their antenatal care overall and views on specific aspects of their antenatal care., Results: Women in shared care (n = 151) were not more likely than women in public clinic care (n = 143) to rate their care as "very good" (odds ratio [OR], 1.38; 95% confidence interval [95% CI], 0.72-2.63). Satisfaction with particular aspects of care (waiting times, opportunity to ask questions, whether caregivers were rushed, whether concerns were taken seriously) did not differ significantly between those in shared care and those in public clinic care. Women in shared care were not happier with their medical care than women in public clinic care (OR, 0.83; 95% CI, 0.35-1.96), but were more likely to see a caregiver who spoke their language (OR, 17.69; 95% CI, 6.15-69.06), although two-thirds still saw a GP who spoke only English., Conclusion: Shared antenatal care is not more satisfying than public clinic care for women from non-English-speaking backgrounds. Further evaluation of shared care is clearly needed.

Several dozen lung epithelial cell lines have been established in culture over the past 20 years from normal lung explants and their spontaneous transformants, and from lung tumors that arose spontaneously or were induced with chemicals, viruses, or oncogenic transgenes. To provide information from which to choose appropriate lines for investigating problems in lung cell biology and pulmonary neoplasia, this review describes the origins of these lines and some of their characteristics. These include growth, morphology, tumorigenicity, ability to metastasize, xenobiotic metabolism, mutational status, signal transducing activities, cytogenetics, ability to form domes, and electric conductance. In addition to collecting this information in a single place for the first time, we describe previously unpublished apoptosis features of some of these lines. An increasing number of investigations are beginning to use these lines and this review contains references into 1997.

The health of a Hmong woman had been deteriorating since she underwent caesarean section. She believes that her ill health is caused by her soul leaving her body during general anaesthesia. A caesarean was essential for the survival of the fetus, but it could have been better managed. The situation might have been prevented if the cultural beliefs and practices of the Hmong had been taken into account. Nevertheless, the agreement of the hospital to a soul calling ceremony in the operating theatre and the concerns expressed by hospital staff about her well-being are positive aspects, showing that mainstream health services can provide culturally sensitive care to consumers if they are informed of these cultural beliefs and practices.

Thirty women were interviewed and divided into active and sedentary groups. Pre-delivery data, information regarding labor and delivery, Apgar scores of the newborn and perceived exertion during labor were recorded and statistically analyzed. Neonates of active women showed slightly higher one-minute Apgars and no difference in fetal weight or five-minute Apgars. Active women indicated lower perceived exertion during labor, longer delivery times and no differences in gestational length, maternal weight gain and time during the first stage of labor. Maternal weight gain in both groups correlated positively with fetal weight. A higher fetal weight indicated a slightly higher five-minute Apgar. Primaparas showed no difference in the first stage of labor although longer delivery time was noted. No differences in levels of medication during labor were revealed although the youngest and oldest subjects required cesarean delivery. Obese women labored longer, indicated higher perceived exertion and higher fetal weights.

Cytotoxic T lymphocytes (CTL) were generated in C57BL/6 mice with herpes simplex virus type 1 (HSV-1) (strains KOS, 17, HFEM, and mP) and HSV-2 (strains 186, G, and GP6). Effector lymphocytes were tested for cytotoxicity against syngeneic HSV-1- and HSV-2-infected cells in a 5-h 51Cr release assay. HSV-1 strain HFEM was found to induce CTL efficiently only when 100-fold more virus was used as compared with HSV-1 strains KOS, 17, and mP. All HSV-1 and HSV-2 strains induced cross-reactive populations of CTL. CTL generated by HSV-1 KOS and HSV-2 186 also demonstrated cross-reactivity in an ear-swelling model for delayed-type hypersensitivity. Lymphocytes generated by all HSV-2 strains were highly efficient at lysing HSV-1-infected target cells. However, HSV-2-infected target cells were found to be less susceptible to lysis by either HSV-1 or HSV-2 CTL than were HSV-1-infected target cells. The lowered susceptibility of HSV-2-infected cells was not due to an inefficient infection of BL/6 WT-3 cells as measured by standard growth assays and infectious center assays. Varying the multiplicity of infection or the time of infection did not increase the susceptibility of HSV-2-infected target cells to lysis by CTL. Increasing the effector-to-target-cell ratio resulted in an increased lysis of both HSV-1- and HSV-2-infected target cells by CTL, but the level of HSV-2-infected target cell lysis still did not approach the level of HSV-1-infected target cell lysis. HSV-2-infected cells were as efficient as HSV-1-infected cells in the cold cell competition assay employed in reducing the lysis of 51Cr-labeled, HSV-1-infected target cells. In addition, HSV-2-infected cells were susceptible to lysis by HSV-immune serum and complement.

The objective of this study was to identify and test a convenient means for long-term storage of lymphocytes taken from clinically characterized patients without losing B- or T-cell function. Accordingly, peripheral blood lymphocytes were frozen and stored, and portions of each sample were subsequently assayed for T-cell blastogenic response and B-cell Jerne plaquing at various time intervals after freezing. A comparison of the cell counts of fresh and frozen cultures indicated that cell were recovered after freezing. Furthermore, these cells showed no significant differences in (i) cell viability; (ii) blastogenic response to antigens of Actinomyces maeslandii, Bacteroides melaninogenicus, Fusobacterium nucleatum, and tetanus toxoid; (iii) blastogenic response to phytohemagglutinin and pokeweed mitogen; and (iv) polyclonal B-cell response to pokeweed mitogen as measured by the direct Jerne plaque assay. The retained blastogenic and plaquing responses seen in frozen cultures indicated the maintenance of both T-cell and B-cell function, respectively. This is the first reported demonstration of Jerne plaquing of normal human lymphocytes after freezing. It appears that freezing techniques provide a means for repeating and extending both T- and B-cell assays using frozen stored portions of the same cell samples.

Fifty-four patient had coexisting stenosis of the carotid artery (70% or greater) and coronary artery disease. Simultaneous carotid endarterectomy and myocardial revascularization were done in all cases. One permanent postoperative neurologic deficit occurred (1.9%). There were no deaths. Our experience with simultaneous correction of combined carotid and coronary disease leads us to conclude that simultaneous myocardial revascularization and carotid endarterectomy have low mortality and neurologic morbidity rates. The policy at Loyola University Medical Center at this time is to routinely perform simultaneous endarterectomy and myocardial revascularization in all patients with significant coexisting carotid and coronary disease.

The ages and the symptoms of patients who have left atrial myxomas and coronary artery disease are similar. Two patients in whom both lesions coexisted were successfully operated on. Based on this experience, it is recommended that coronary cineangiography be performed on patients with left atrial myoxmas when a positive anginal history is obtained or when the patient is over 35 years of age. In the patient with coexisting myxoma and coronary artery disease, careful preoperative planning for myocardial protection is advised.

A function(s) involved in the altered susceptibility of herpes simplex virus type 2 (HSV-2)-infected cells to specific lysis by cytotoxic T lymphocytes was mapped in the S component of HSV-2 DNA by using HSV-1 X HSV-2 intertypic recombinants (RH1G44, RS1G25, R50BG10, A7D, and C4D) and HSV-1 MP. Target cells infected with R50BG10, A7D, and C4D exhibited reduced levels of cytolysis, as did HSV-2-infected cells, whereas RH1G44 and RS1G25 recombinant-infected and HSV-1 MP-infected cells showed levels of lysis equal to that of HSV-1 KOS-infected cells. The intertypic recombinants R50BG10, RS1G25, RH1G44, and HSV-1 MP induced cross-reactive cytotoxic T lymphocytes. Coinfection of cells with HSV-1 KOS and either HSV-2 186 or R50BG10 recombinant also resulted in a decrease in the level of specific lysis by anti-HSV cytotoxic T lymphocytes.

We determined whether (1) long term antigen retention is present in distal sites after footpad challenge of immune mice; (2) if antigen retained in the foot is selectively localized; and (3) if the foot is adversely affected by the retained antigen. Mice immune or non-immune to human serum albumin (HSA) were injected in the hind footpads with 125I-HSA. In immune mice rapid clearance of radiolabel occurred in the liver, lungs, kidney, blood and urine but radiolabel was retained in the hind feet, draining lymph nodes and spleen. Non-immune mice rapidly cleared radiolabel from these sites. Autoradiography revealed that most of the radiolabel in the feet was in flexor tendons and tendon sheaths. Electron microscope autoradiography indicated that antigen was associated with collagen at the tendon surface, but not with cells or cell processes. Radiolabel solubilized from the feet, lymph nodes and spleen could be specifically precipitated with rabbit anti-HSA. Histological examination of the tendon and surrounding tissues did not show that retained antigen was causing inflammation or chronic tissue damage. Nanogram levels of antigen could elicit swelling in the sensitized foot even if the antigen was injected at a remote site, but mice immunized by other routes or against other antigens did not show footpad swelling. Antigen retained on collagenous tissues may induce hypersensitivity and thus play a role in rheumatic diseases.

One lung of each dog was exposed to smoke from burning pine wood, while the other was subjected to acute hypoxia. Angiotensin-1-converting enzyme (ACE) activity in biopsied tissue of the smoke-exposed lung was markedly increased immediately after the injury and even higher 30 minutes later. No change in ACE activity was observed in the hypoxic contralateral lung. Serum ACE activity did not change significantly following anesthesia and before smoke inhalation. Serum aldosterone and cortisol levels increased at this juncture. Smoke inhalation caused intra-alveolar hemorrhages and edema. Pulmonary and systolic, diastolic and mean pressures, pulmonary capillary, wedge pressure, cardiac output and systemic and pulmonary arteriolar resistances remained unchanged throughout the experiment. The changes of ACE activity are presumably a direct effect of smoke inhalation. They are seen as an early response of the lung endothelial cells to many types of injury (chronic hypoxia, bleomycin or monocrotaline administration) and may represent an important step in the development of the organ's response to the injury.