Antioxidant network expression abrogates oxidative posttranslational modifications in mice.

Antioxidant enzymatic pathways form a critical network that detoxifies ROS in response to myocardial stress or injury. Genetic alteration of the expression levels of individual enzymes has yielded mixed results with regard to attenuating in vivo myocardial ischemia-reperfusion injury, an extreme oxidative stress. We hypothesized that overexpression of an antioxidant network (AON) composed of SOD1, SOD3, and glutathione peroxidase (GSHPx)-1 would reduce myocardial ischemia-reperfusion injury by limiting ROS-mediated lipid peroxidation and oxidative posttranslational modification (OPTM) of proteins. Both ex vivo and in vivo myocardial ischemia models were used to evaluate the effect of AON expression. After ischemia-reperfusion injury, infarct size was significantly reduced both ex vivo and in vivo, ROS formation, measured by dihydroethidium staining, was markedly decreased, ROS-mediated lipid peroxidation, measured by malondialdehyde production, was significantly limited, and OPTM of total myocardial proteins, including fatty acid-binding protein and sarco(endo)plasmic reticulum Ca(²+)-ATPase (SERCA)2a, was markedly reduced in AON mice, which overexpress SOD1, SOD3, and GSHPx-1, compared with wild-type mice. These data demonstrate that concomitant SOD1, SOD3, and GSHPX-1 expression confers marked protection against myocardial ischemia-reperfusion injury, reducing ROS, ROS-mediated lipid peroxidation, and OPTM of critical cardiac proteins, including cardiac fatty acid-binding protein and SERCA2a.

Modulation of N-myc expression alters the invasiveness of neuroblastoma.

N-myc oncogene expression plays a pivotal role in the biology of neuroblastoma, a common childhood tumor. High N-myc expression is associated with advanced disease stage, and in animal models, increased expression results in increased metastatic potential. In normal embryologic development, N-myc expression is associated with neuroblast migration out from the neural crest. To further define the relationship between N-myc and metastasis, an in vitro assay was adapted to measure tumor cell attachment, motility, and proteolytic ability in neuroblastoma cell lines. These parameters were examined in a non-amplified, uniformly N-myc overexpressing cell line and its anti-sense N-myc expressing clones. These lines have been characterized previously, and have a decrease in N-myc expression, growth rate, and tumorigenicity relative to the parent line and vector-only control transfectant. Decrease in N-myc expression resulted in a non-proportional increase of tumor cell attachment, and a proportional decrease in both tumor cell motility and proteolytic ability. In further experiments, assay of a N-myc-amplified overexpressing cell line with an intrinsic heterogeneous pattern of expression demonstrated that motile cells expressed higher amounts of N-myc relative to the general population. Together these relationships indicate that N-myc plays a causative role in the invasive phenotype, and suggest that metastasis may, in part, result from the disruption of a developmentally important normal process.

Acinic cell carcinoma of the lacrimal gland.

An 18-year-old woman underwent exenteration of the right orbit for tumor recurrence 3 years subsequent to external-beam irradiation for a lacrimal gland tumor diagnosed as an "adenocarcinoma." Light microscopy of the exenteration specimen revealed an acinic cell carcinoma of the lacrimal gland, with a predominant microcystic (latticelike) pattern of growth. Cytoplasmic vacuoles and the secretion within the microcysts stained positive with periodic acid-Schiff with and without alpha-amylase, alcian blue (at a pH of 2.5), mucicarmine, and colloidal iron with and without hyaluronidase. This histochemical staining for epithelial mucins supports the theory that the lacrimal gland, although serous in type, may also function as a modified mucus gland. There was cytoplasmic immunopositivity for keratin (CAM 5.2, KAE 1-3); immunostaining for vasoactive intestinal polypeptide was negative. Electron microscopy disclosed undifferentiated features of intercalated duct cells. We speculate that the lack of immunoreactivity for vasoactive intestinal polypeptide may be correlated with the predominantly undifferentiated intercalated duct cell features observed ultrastructurally.

Pregnancy after bromocriptine-induced reduction of an extrasellar prolactin-secreting pituitary macroadenoma.

In patients with a large prolactin-secreting pituitary adenoma, a marked reduction in tumor size may be achieved with bromocriptine therapy. However, before consideration of pregnancy, surgical removal of the lesion usually is advised. A 36-year-old woman with a large extrasellar pituitary macroadenoma was treated with bromocriptine, 10 mg/day, which resulted in dramatic reduction of the tumor mass. Subsequently, she became pregnant and drug therapy was maintained throughout gestation. This case illustrates the use of bromocriptine in the management of large prolactin-secreting pituitary tumors and the necessity for adequate radiologic follow-up.

Physical and sexual assault history in women with serious mental illness: prevalence, correlates, treatment, and future research directions.

An emerging body of research on the physical and sexual abuse of seriously mentally ill (SMI) women documents a high incidence and prevalence of victimization within this population. While causal links are not well understood, there is convergent evidence that victimization of SMI women is associated with increased symptom levels, HIV-related risk behaviors, and such comorbid conditions as homelessness and substance abuse. These abuse correlates may influence chronicity, service utilization patterns, and treatment alliance. This article reviews the research literature on the prevalence, symptomatic and behavioral correlates, and treatment of abuse among SMI women, particularly women with schizophrenia. Within each topic, we discuss relevant research findings, limitations of available studies, and key questions that remain unanswered. We also discuss mechanisms that may underlie the relationship between trauma and schizophrenia-spectrum disorders. We conclude by outlining directions for future research in this area.

Elevated GM2 ganglioside is associated with dendritic proliferation in normal developing neocortex.

Mature pyramidal neurons of cerebral cortex in several neuronal storage diseases elaborate ectopic dendrites. These dendrites appear specifically on pyramidal neurons containing elevated GM2 ganglioside and a variety of studies support the hypothesis that this ganglioside is responsible for inducing the new dendrite growth. To determine whether a similar association between GM2 ganglioside and dendrite growth occurs in normal neurons, we used an antibody to localize GM2 in developing cat neocortex. Our results show that GM2 ganglioside is elevated in normal cortical neurons during the period when dendritogenesis is occurring, but is greatly diminished in these cells after dendritic differentiation is complete. Elevations of GM2 occur in deep neurons earlier than in superficial ones, a sequence that corresponds closely to the inside-first, outside-last progression of cortical neuron differentiation. Ultrastructurally, GM2 immunoreactivity is found sequestered in vesicles with a distribution that coincides with sites of ganglioside synthesis and transport. The close association between elevated GM2 ganglioside and dendrite growth in cortical pyramidal neurons during normal development, coupled with a similar correlation between GM2 and ectopic dendritogenesis in neuronal storage diseases, support the view that this specific ganglioside plays a pivotal role in regulating dendritogenesis.

The effect of the ergoline derivative, CU 32-085, on prolactin secretion in hyperprolactinemic women.

Twelve hyperprolactinemic women were administered the alpha aminoergoline derivative, CU 32-085 (Sandoz, Inc., East Hanover, NJ), in order to determine its effect on prolactin (PRL) secretion. The mean pretreatment serum PRL level was 145.0 +/- 11.5 ng/ml. Significant declines of serum PRL occurred with total daily doses of CU 32-085 of 0.1 to 0.5 mg (P less than 0.001). The magnitude of response to therapy was dose-related. In six patients, PRL levels were reduced to less than 25 ng/ml; this effect lasted at least 24 hours after intake of a single dose. In the other six patients, the response was less dramatic. No subjects developed adverse cardiovascular side effects. The results of this study demonstrate that CU 32-085 exhibits a clinically significant dopaminomimetic action on PRL secretion in hyperprolactinemic women.

Male violence against women. Current research and future directions.

This Psychology in the Public Forum section, authored by the American Psychological Association's Committee on Women in Psychology's Task Force on Male Violence Against Women and by Senator Joseph Biden, examines the prevalence, impact, and public policy dimensions of physical assault, sexual assault, and sexual harassment of women. This introduction reviews common themes that emerge from the articles that follow. It concludes by emphasizing that the problem of violence against women cannot be fully understood, let alone solved, by focusing exclusively on individual psychology. Only by changing the social and cultural institutions that have given rise to the problem can a lasting solution be achieved.

HIV risk factors among people with severe mental illness in urban and rural areas.

No studies have reported HIV risk behavior in rural populations with severe mental illness. A total of 84 rural patients with severe mental illness in New Hampshire and 158 urban patients in Baltimore were interviewed about their HIV risk behavior in the past six months using the Risk Assessment Battery, a 38-item structured clinical interview. Rates of sexual and drug risk behavior among rural patients were significantly lower than among urban patients. Regression analyses showed that urban setting, younger age, never having been married, and a bisexual or gay orientation significantly predicted higher HIV risk scores. The differences in risk behaviors may reflect urban-rural differences in drug availability and sexual practices.

The prevalence of abuse among homeless and housed poor mothers: a comparison study.

The history of physical and sexual abuse among 50 homeless and 50 housed poor mothers was compared, with particular attention to details of prevalence, type, and severity. No significant differences were found except in higher reported rates of sexual abuse in adulthood among housed mothers. However, 89% of the total sample reported experiencing some form of abuse in their lifetimes. The unexpected lack of differential and the high prevalence rates are discussed in terms of service delivery and social policy implications.

HIV risk-behavior in poor urban women with serious mental disorders: association with childhood physical and sexual abuse.

Associations between childhood sexual and physical abuse and HIV-related risky behavior were examined among low-income, urban women with severe mental disorders. Early sexual abuse was found to be related to adult sexual and physical assault, alcohol and cocaine abuse, and prostitution; childhood physical abuse was related to adult physical assault and alcohol abuse. Findings highlight the importance of making HIV risk-reduction programs a part of integrated services that address a full range of psychosocial needs.

Episodically homeless women with serious mental illness: prevalence of physical and sexual assault.

Three aspects of physical and sexual assault in the histories of 99 episodically homeless, seriously mentally ill women were assessed: lifetime prevalence; severity, co-occurrence, and recency; and associations between levels of this victimization and specific characteristics of the women. Results indicate that the life-time risk for violent victimization was so high (97%) as to amount to normative experiences for this population.

The relationship between victimization and cognitive schemata among episodically homeless, seriously mentally ill women.

This study explored the extent to which specific aspects of violent victimization are associated with cognitive schemata in the context of ongoing, often lifelong, trauma and negative life events. Specifically, we examined the relationships between cognitive schemata (safety, self- and other esteem, intimacy, and trust) and three dimensions of physical and sexual assault histories (recentness, frequency, and variety) among 91 predominantly African American, episodically homeless, seriously mentally ill women. Findings indicated that even in the context of pervasive violence, more frequent, recent, and varied abuse was associated with more negative cognitive schemata. We discuss these findings in the context of research and practice with disenfranchised populations at high risk for violent victimization.

Court-involved battered women's responses to violence: the role of psychological, physical, and sexual abuse.

Failure to understand the importance of psychological abuse as a component of domestic violence can result in little appreciation for the complexity of victims' experience and thus a failure to provide the most effective intervention. This study examined the role of psychological abuse, physical violence, injury, and sexual abuse in predicting court-involved women's (1) prior attempts to seek help from the justice system and to leave the battering relationship, (2) use of criminal prosecution and civil protection orders, and (3) traumatic stress reactions. At the univariate level, each abuse variable was significantly associated with at least one strategic response and all traumatic responses to violence. Multivariate analyses revealed that strategic responses were largely predicted by injury and physical assault, whereas traumatic responses were mainly predicted by psychological abuse. Taken together, these findings demonstrate the important role of both physical and psychological abuse in shaping women's responses to domestic violence.

5-Lipoxygenase expression in benign and malignant canine prostate tissues.

5-Lipoxygenase (5-LO) is overexpressed in human prostate carcinomas (PCs), and its inhibition decreases proliferation and induces apoptosis in prostate cancer cell lines. We hypothesized that 5-LO would be overexpressed in canine PC compared with benign prostate tissue and may be important in the pathogenesis of the disease. Immunoblot analysis of canine PC and benign prostatic hyperplasia (BPH) tissues demonstrated 5-LO expression in both. 5-LO immunohistochemical staining was not significantly different within the stromal or epithelial components of canine primary PC, BPH or suppurative prostatitis, suggesting that differential expression of this enzyme does not occur in these conditions. The percentage of tumour cells expressing 5-LO was significantly lower in metastatic PC lesions compared with primary PC (P < 0.0001). This decreased expression may indicate down-regulation or altered expression of the enzyme with progression of canine PC to a metastatic phenotype.

On the age-sex composition of the population that would result from given fertility and mortality conditions.

This article presents new formulas for calculating the eventual sex-ratio and the eventual age-sea composition of the population that would result from given fertility and mortality conditions. These formulas provide more accurate methods and are more widely applicable than earlier methods. The application of the formulas is illustrated through the use of available data on fertility and mortality conditions in the United States in 1964.

The analysis of dependence in cross-classifications having ordered categories, using log-linear models for frequencies and log-linear models for odds.

To analyse the dependence of a qualitative (dichotomous or polytomous) response variable upon one or more qualitative explanatory variables, log-linear models for frequencies are compared with log-linear models for odds, when the categories of the response variable are ordered and the categories of each explanatory variable may be either ordered or unordered. The log-linear models for odds express the odds (or log odds) pertaining to adjacent response categories in terms of appropriate multiplicative (or additive) factors. These models include the 'null log-odds model', the 'uniform log-odds model', the 'parallel log-odds model', and other log-linear models for the odds. With these models, the dependence of the response variable (with ordered categories) can be analyzed in a manner analogous to the usual multiple regression analysis and related analysis of variance and analysis of covariance. Application of log-linear models for the odds sheds light on earlier applications of log-linear models for the frequencies in contingency tables with ordered categories.

Eliminating afferent impulse activity does not alter the dendritic branching of the amphibian Mauthner cell.

In the developing amphibian, the formation of extra vestibular contacts on the Mauthner cell (M-cell) enhances dendritic branching, while deprivation reduces it (Goodman and Model, 1988a). The mechanism underlying the interaction between afferent fibers and developing dendritic branches is not known; neural activity may be an essential component of the stimulating effect. We examined the role of afferent impulse activity in the regulation of M-cell dendritic branching in the axolotl (Ambystoma mexicanum) embryo. M-cells occur as a pair of large, uniquely identifiable neurons in the axolotl medulla. Synapses from the ipsilateral vestibular nerve (nVIII) are restricted to a highly branched region of the M-cell lateral dendrite. We varied the amount of nVIII innervation and eliminated neural activity. First, unilateral transplantation of a vestibular primordium deprived some M-cells of nVIII innervation and superinnervated others. Second, surgical fusion of axolotls to TTX-harboring California newt (Taricha torosa) embryos paralyzed the Ambystoma twin: voltage-sensitive Na+ channel blockade by TTX eliminated action potential propagation. Reconstruction of M-cells in 18 mm larvae revealed that dendritic growth was influenced by in-growing axons even in the absence of incoming impulses: impulse blockade had no effect on the stimulation of dendritic growth by the afferent fibers.

Superinnervation enhances the dendritic branching pattern of the Mauthner cell in the developing axolotl.

Mauthner cells (M-cells) occur as a pair of large, uniquely identifiable neurons at ear level in the hindbrain of premetamorphic amphibians. Each receives synapses from the ipsilateral vestibular nerve (nVIII); these morphologically distinctive terminals, or club endings, are confined to the proximoventral surface and branches of the M-cell lateral dendrite. We have superinnervated this portion of the M-cell to examine the extent to which forming afferent contacts regulate the growth and branching of the lateral dendrite. Superinnervation was brought about in the developing axolotl (Ambystoma mexicanum) by unilaterally implanting an extra vestibular primordium rostral to the in situ one. The contralateral side served as control. When the larvae reached 21 mm in length, the ectopic nerve was labeled with HRP. Subsequent microscopic examination revealed that the grafts developed into anatomically normal ears. The HRP-labeled ectopic axons entered the medulla at the level of nV and confined to the nVIII tract, coursed caudad toward the ipsilateral M-cell. Electron microscopic analysis demonstrated labeled club endings on the appropriate region of the M-cell lateral dendrite. The number of club endings on experimental M-cells was significantly greater than that on the contralateral controls, and the extra terminals appeared to be distributed randomly among unlabeled ones. Comparison of reconstructed experimental and control M-cells revealed that superinnervation produced a localized enhancement of dendritic branching in the region receiving the extra nVIII synapses. In the donor embryos (those from which the vestibular primordium was removed), M-cells were unilaterally deprived of nVIII afferents. Comparison of reconstructed experimental and control M-cells in 21 mm donor larvae demonstrated that deprivation produced a localized decrease of dendritic surface in the region that normally receives nVIII synapses. Together, these data show that ingrowing axons stimulate dendritic growth and thus regulate the development of a normal dendritic branching pattern on target neurons.

Posttraumatic stress disorder among battered women: analysis of legal implications.

The diagnosis of posttraumatic stress disorder (PTSD) has recently been applied to the psychological experiences of victims of intimate violence, including physical and sexual assault. The use of trauma theory to explain battered women's responses to violence has laid a foundation for expert testimony on PTSD, where relevant, within more general testimony concerning partner violence. This article discusses the relevance of the PTSD diagnosis within the legal context for explaining battered women's responses to violence.