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Biomedical subjects

Samuel J Simmens

Publications and source records attributed to Samuel J Simmens.

17 recordsLinked to original sources

Maternal panic disorder: Infant prematurity and low birth weight.

The aim of this pilot research was to investigate whether infants of mothers with panic disorder (PD) would be at higher risk for prematurity and low birth weight (corrected for gestational age) than controls. Medical records were reviewed for 25 mothers with PD and 33 mothers without a lifetime history of anxiety disorders or other major psychopathology as determined by diagnostic interview. Mothers also completed questionnaires concerning demographic information and life stresses. Compared to controls, infants with PD mothers were not significantly more likely to be born prematurely or earlier than controls but did show smaller birth weight corrected for gestational age, even after accounting for possible confounding influences. Additional research is needed to confirm these preliminary findings. Studying PD mothers during pregnancy could provide insight concerning mechanisms for the development of low birth weight and psychopathology.

Adult↗

Maternal depressive symptoms and child sleep: models of mutual influence over time.

The aim of the research was to test hypotheses concerning the associations between maternal depressive symptoms and child sleep using longitudinal data to examine possible predictive pathways. Data from the National Institute of Child Health and Human Development Study of Early Child Care with 1222 children studied from 1 to 36 months of age were analyzed to examine: effects on trajectories over time, and phase-specific effects over three defined age periods (6 to 15, 15 to 24, and 24 to 36 months). Child sleep was found to influence maternal depressive symptoms only for the 15- to 24-month age period, where, contrary to expectation, longer duration of child awakenings predicted decreased maternal depressive symptoms. Maternal depressive symptoms were found to predict an increased frequency of child awakenings across the 15- to 24-month age period only. In contrast, maternal depressive symptoms were found to significantly predict increased duration of child awakenings both for the 3-year trajectory and across the 15- to 24- and 24- to 36-month age periods. Additional research is needed to clarify the mechanisms by which maternal depressive symptoms predict increased duration of child awakenings.

Adult↗

Toddler anxiety disorders: a pilot study.

OBJECTIVE: This research examined the validity of criteria for diagnosing social phobia (SOC) and generalized anxiety disorder (GAD), where the DSM-IV criteria were modified to better identify toddlers who could have these disorders. METHOD: Diagnoses were made with a semistructured clinical interview that included child observations. Parents and caregivers completed child behavior, temperament, and socioemotional functioning questionnaires to test convergent and discriminant validity. RESULTS: Of 72 children, 18 months to 5 years old, 19 met modified SOC criteria (8 met DSM-IV criteria SOC also), 29 met modified GAD criteria (5 met DSM-IV criteria GAD also), and 35 met no anxiety disorder criteria. Children with modified SOC were more likely than nonanxious children to display higher levels of anxiety symptoms and shyness/inhibition and to have anxious parents. Modified SOC did not relate to the nonanxiety constructs (cuddling, imaginary play, fine motor). Children with modified GAD did not consistently demonstrate higher levels of anxiety symptoms, did not have more anxious parents than nonanxious children, and did not have higher mean scores on the nonanxiety constructs. CONCLUSIONS: This research provides initial evidence supporting convergent and discriminant validity for the modified SOC criteria but not the modified GAD criteria.

Anxiety Disorders↗

The effects of pulsed 860 MHz radiofrequency radiation on the promotion of neurogenic tumors in rats.

In a previous study, this laboratory reported a statistically nonsignificant trend for shortened latency of ethylnitrosourea (ENU)-induced brain tumors in Sprague-Dawley rats exposed to an 860 MHz pulsed radiofrequency (RF) signal. The present study was designed to investigate further any promoting effect of the pulsed RF signal on latency and other characteristics of neurogenic tumors in the progeny of pregnant rats treated with 6.25 or 10 mg/kg ENU. The resulting 1080 offspring were randomized equally by number, sex and ENU dose into pulsed RF, sham and cage control groups. The rats were exposed to the pulsed RF signal 6 h per day 5 days per week; the sham-exposed group was similarly confined for the same periods, and the cage controls were housed in standard cages. An essentially equal number of rats from each group were killed humanely every 30 days between the ages of 171 and 325 days; 32 rats died and 225 rats were killed when they were moribund. Postmortem examinations on the 1080 rats revealed 38 spinal cord tumors, 191 spinal nerve tumors, 232 cranial nerve tumors, and 823 brain tumors. A methodical study of the tumor characteristics disclosed no evidence that exposure to the pulsed RF signal affected the incidence, malignancy, volume, multiplicity, latency or fatality associated with any kind of neurogenic tumor.

Animals↗

Integrins in slow-cycling corneal epithelial cells at the limbus in the mouse.

Adult corneal epithelial stem cells (CESCs) have been shown to reside at the periphery of the cornea at a site called the corneoscleral junction or limbus. Although studies have shown that these cells are slow cycling, their molecular characteristics are not well understood. Using a whole-mount procedure, we show that whereas alpha9-integrin is present in a subset of the basal cells at the corneal limbus and absent in the central cornea, beta1-, beta4-, alpha3-, and alpha6-integrins are more highly expressed overall in central corneal basal cells. To characterize CESCs based on their slow-cycling nature, we simultaneously evaluated 5-bromo-2-deoxyuridine (BrdU) label-retaining cells (LRCs) and integrin expression (alpha9, beta1, and beta4) in a total of 1,889 cells at the limbus of adult mice that had been injected as neonates with BrdU. Whereas the LRCs were usually observed adjacent to alpha9-integrin-positive cells, most LRCs were alpha9-integrin-negative and expressed high levels of beta1- and beta4-integrin. In addition, we observed more BrdU-positive LRCs at the superior and inferior quadrants of adult mouse corneas than at the nasal and temporal quadrants, and determined that 0.94 to 3.6% of the limbal basal cells were slow cycling. We conclude from these data that the slow-cycling LRCs in the adult mouse cornea are enriched in cells that express high levels of beta1- and beta4-integrin and little alpha9-integrin.

Animals↗

Expression of BP1, a novel homeobox gene, correlates with breast cancer progression and invasion.

BACKGROUND: Our previous studies revealed that the mRNA encoded by BP1, a member of the homeobox gene superfamily of transcription factors, was expressed in leukemia and infiltrating breast ductal carcinoma (IDC). This study investigated the immunohistochemical profile of BP1, to determine whether the expression of BP1 protein correlated with breast tumor progression and invasion and whether BP1 was co-localized with erbB2. DESIGN: Paraffin sections from normal reduction mammoplasties (n = 34) and a variety of in situ and invasive breast cancers (n = 270) were either singly immunostained for BP1, or doubly immunostained for BP1 plus either erbB2 or Ki-67. RESULTS: The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and carcinogenesis. BP1 expression was barely detectable in normal reduction mammoplasties compared to distinct staining in 21, 46, and 81% of hyperplastic, in situ, and infiltrating lesions, respectively. In cases with co-existing normal, hyperplastic, in situ, and invasive lesions, the tumor cells of the invasive lesions consistently showed the highest frequency and the highest intensity of BP1 immunostaining, followed by in situ tumor cells. Double immunostaining revealed that BP1 co-localized with a subset of erbB2 positive cells in all 15 in situ and IDC tumors examined, and that BP1 positive cells had a substantially higher proliferation rate than morphologically similar cells without BP1 expression. CONCLUSION: These findings suggest that BP1 is an important upstream factor in an oncogenic pathway, and that expression of BP1 may reliably reflect or directly contribute to tumor progression and/or invasion.

Breast Neoplasms↗

Neurogenic tumors in rats induced by ethylnitrosourea.

Ethylnitrosourea (ENU) was injected intravenously into Sprague-Dawley rats on day 15 of gestation at doses of 0, 2.50, 6.25 and 10.00 mg/kg. The resulting 1980 progeny were observed for up to 24 months in a life-time study (900 rats) or for periods of 171-325 days in a serial sacrifice study (1080 rats). The rats in both studies were randomized into three groups, one exposed to a radiofrequency, one sham-exposed and one cage control. Since no effects of the radiofrequency were observed on the ENU-induced tumors, the exposure groups were combined to facilitate study of the tumors by dose rate over time. All rats were necropsied and major organs were examined histologically including the brain, entire spinal cord, trigeminal nerves and all tumors. A total of 48 spinal cord tumors (SCT), 251 spinal nerve tumors, 264 cranial nerve tumors and 1058 brain tumors were studied. The tumors were characterized by incidence, histologic type, volume, malignancy and multiplicity. Ethylnitrosouria, as given in this study, was determined to be an effective carcinogen reliably inducing (in order of frequency) brain, cranial nerve, spinal nerve and SCT. Dose of ENU correlated positively with the frequency, multiplicity, volume, malignancy, and negatively with latency of brain tumors and to a lesser extent with nerve tumors.

Alkylating Agents↗

Dependable social relationships predict overall survival in Stages II and III breast carcinoma patients.

OBJECTIVE: The effect of support, from dependable non-household relationships, on breast cancer progression was studied using a prospective, longitudinal design. METHODS: Dependable social support was assessed in women with invasive breast carcinoma Stages II and III within 18 months after diagnosis. Disease outcome was monitored for 8 to 9 years. Cox regression analyses, including the Nottingham Prognostic Index (NPI) score of disease severity, tested the association between the number of dependable support persons and time to death. RESULTS: Ninety participants listed between 1 and 16 dependable nonhousehold support persons (mean = 6, S.D. = 4). There were 21 recurrences and 16 deaths from breast cancer at the end of the study. The number of dependable supports predicted decreased mortality [RR = 0.41 (0.21-0.80), P = .01] after controlling for NPI. NPI predicted increased mortality [RR = 1.6 (1.0, 2.4), P = .05]. CONCLUSIONS: For patients with Stages II and III breast cancer, the number of dependable, nonhousehold relationships predicts decreased mortality, after accounting for disease severity.

Adult↗

Is testicular cancer related to Gulf War deployment? Evidence from a pilot population-based study of Gulf War era veterans and cancer registries.

The possible relationship between military deployment and the subsequent increase in cancer rates has been prominent since the Vietnam War. The objective of this study was to investigate whether any form of cancer was increased among veterans deployed to the Persian Gulf in the 1991 conflict. This study matched data from central cancer registries in the District of Columbia and New Jersey with the records for 1.4 million Gulf War era veterans, i.e., 621,902 veterans who arrived in the Persian Gulf before March 1, 1991, and 746,248 non-Gulf veterans. Using a proportional incidence ratio, testicular cancer was found to be the only significantly increased malignancy among deployed Persian Gulf War veterans. The increase became apparent 2 to 3 years after the Persian Gulf War and peaked 4 to 5 years afterward. Our data and those of investigators studying Vietnam veterans suggest that testicular cancer may be related to military deployment.

Adult↗

Prenatal nicotine exposure alters central cardiorespiratory responses to hypoxia in rats: implications for sudden infant death syndrome.

Maternal cigarette smoking and prenatal nicotine exposure are the highest risk factors for sudden infant death syndrome (SIDS). During hypoxia, respiratory frequency and heart rate transiently increase and subsequently decrease. These biphasic cardiorespiratory responses normally serve to prolong survival during hypoxia by reducing the metabolic demands of cardiac and respiratory muscles. However, exaggerated responses to hypoxia may be life threatening and have been implicated in SIDS. Heart rate is primarily determined by the activity of brainstem preganglionic cardioinhibitory vagal neurons (CVNs) in the nucleus ambiguus. We developed an in vitro rat brainstem slice preparation that maintains rhythmic inspiratory-related activity and contains fluorescently labeled CVNs. Synaptic inputs to CVNs were examined using patch-clamp electrophysiological techniques. Hypoxia evoked a biphasic change in the frequency of both GABAergic and glycinergic IPSCs in CVNs, comprised of an initial increase followed by a decrease in IPSC frequency. Prenatal exposure to nicotine changed the GABAergic response to hypoxia from a biphasic response to a precipitous decrease in spontaneous GABAergic IPSC frequency. This study establishes a likely neurochemical mechanism for the heart rate response to hypoxia and a link between prenatal nicotine exposure and an exaggerated bradycardia during hypoxia that may contribute to SIDS.

Action Potentials↗

Correlation of expression of BP1, a homeobox gene, with estrogen receptor status in breast cancer.

BACKGROUND: BP1 is a novel homeobox gene cloned in our laboratory. Our previous studies in leukemia demonstrated that BP1 has oncogenic properties, including as a modulator of cell survival. Here BP1 expression was examined in breast cancer, and the relationship between BP1 expression and clinicopathological data was determined. METHODS: Total RNA was isolated from cell lines, tumors, and matched normal adjacent tissue or tissue from autopsy. Reverse transcription polymerase chain reaction was performed to evaluate BP1 expression. Statistical analysis was accomplished with SAS. RESULTS: Analysis of 46 invasive ductal breast tumors demonstrated BP1 expression in 80% of them, compared with a lack of expression in six normal breast tissues and low-level expression in one normal breast tissue. Remarkably, 100% of tumors that were negative for the estrogen receptor (ER) were BP1-positive, whereas 73% of ER-positive tumors expressed BP1 (P = 0.03). BP1 expression was also associated with race: 89% of the tumors of African American women were BP1-positive, whereas 57% of those from Caucasian women expressed BP1 (P = 0.04). However, there was no significant difference in BP1 expression between grades I, II, and III tumors. Interestingly, BP1 mRNA expression was correlated with the ability of malignant cell lines to cause breast cancer in mice. CONCLUSION: Because BP1 is expressed abnormally in breast tumors, it could provide a useful target for therapy, particularly in patients with ER-negative tumors. The frequent expression of BP1 in all tumor grades suggests that activation of BP1 is an early event.

Breast Neoplasms↗

Anthropometric measures, cytokines and survival in haemodialysis patients.

BACKGROUND: Lower serum albumin concentration (sAlb) and higher levels of pro-inflammatory cytokines have been reported to predict death in patients treated with haemodialysis (HD). SAlb, along with anthropometric measures, has been used as a surrogate marker for nutritional status in patients with chronic disease. Though adequate nutrition has been considered an important factor for patients treated with HD, it has not been established if any nutritional markers other than lower serum albumin and lower body mass index (BMI) predict death. Furthermore, it has not been shown whether anthropometric measures other than BMI are associated with predictors of mortality. METHODS: At the outset of the study, patients were assessed using demographic and anthropometric indices including arm fat area (AFA), arm muscle area (AMA), BMI, per cent ideal weight (PIW), pre-dialysis sAlb, and circulating levels of tumour necrosis factor-alpha (TNF-alpha), IL-1 and IL-6. A severity index, previously demonstrated to be a mortality marker, was used to grade medical co-morbidity. RESULTS: Two-hundred and forty patients entered the study. The mean age was 55.1+/-14.3 years, mean sAlb 3.76+/-0.60 mg/dl, mean AFA 1742+/-1225 mm(2), mean AMA 5464+/-1817 mm(2), mean PIW 101.0+/-21.3% and mean BMI 24.9+/-5.6 kg/m(2). PIW, BMI, AFA and AMA were, as expected, all highly correlated with one another. SAlb correlated with serum transferrin; however, neither sAlb nor serum transferrin concentration correlated with circulating cytokine levels. Circulating cytokines and sAlb did not correlate with PIW, BMI, AFA or AMA. In Cox regression analyses using multiple control variables, IL-6 predicted survival, while the anthropometric measures did not. CONCLUSIONS: Pro-inflammatory cytokines and sAlb are robust predictors of death in patients treated with HD. PIW and BMI correlate well with other anthropometric measures in patients treated with HD, but these measures do not correlate with markers of inflammation. Anthropometric measures are poor predictors of survival compared with measures linked to the acute-phase response.

Adipose Tissue↗

Maternal panic disorder: infant temperament, neurophysiology, and parenting behaviors.

OBJECTIVE: To determine whether 4- and 14-month-old infants of mothers with panic disorder (PD) would be more likely to show differences in temperament, neurophysiology (salivary cortisol and sleep), and relationships with their mothers than controls. METHOD: Two cohorts were recruited: 4-month-old infants with PD mothers (n = 25) and 4-month-old controls (n = 24), and 14-month-old infants with PD mothers (n = 27) and 14-month-old controls (n = 18). Mothers completed diagnostic interviews and questionnaires concerning infant temperament, sleep, and parenting. Infant salivary cortisol samples and standard observational procedures to measure infant temperament, sleep, attachment, and parenting were also used. RESULTS: Infants with PD mothers did not show more high reactivity, behavioral inhibition, or ambivalent/resistant attachment but did demonstrate different neurophysiology (higher salivary cortisol and more disturbed sleep) than controls. PD mothers also displayed less sensitivity toward their infants and reported parenting behaviors concerning infant sleep and discipline that have been associated with child problems. CONCLUSIONS: While infants with PD mothers did not show early behavioral differences from controls, they did display neurophysiological divergences consistent with higher arousal/arousability. Such neurophysiological divergences (elevated salivary cortisol and disturbed sleep) might be important early indicators of risk. Helping PD mothers parent their more highly aroused/arousable infants could reduce the development of psychopathology.

Adult↗

Factor analysis of fatiguing syndrome in Gulf War era veterans: implications for etiology and pathogenesis.

This study used factor analysis to identify possible subgroups of symptoms of fatiguing syndrome (FS). Subjects were classified with FS according to the 1994 modified Centers for Disease Control and Prevention criteria with the exception that the chronicity of excessive fatigue could not be documented. The cases consisted of 640 Gulf War veterans who met the criteria, whereas the control groups were composed of 5417 Gulf War and 6493 non-Gulf War veterans who did not meet the criteria and had none of the medical conditions that were exclusionary in the FS group. Factor analyses were performed separately in each group. Factor analysis revealed 6 subgroups: fatigue, pain, infectious, gastrointestinal, respiratory, and neurologic/mood/fatigue. Although the factors were similar for both groups, they were more differentiated in the FS group than in the control group as evidenced by interfactor correlations.

Adult↗

Treatment expectancies, patient alliance, and outcome: further analyses from the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

Prior analyses from the National Institute of Mental Health Treatment of Depression Collaborative Research Program indicated that patients' expectancies of treatment effectiveness (S. M. Sotsky et al., 1991) and the quality of the therapeutic alliance (J. L. Krupnick et al., 1996) predicted clinical improvement. These data were reanalyzed to examine the hypothesis that the link between treatment expectancies and outcome would be mediated by patients' contribution to the alliance. Among 151 patients who completed treatment, this hypothesis was supported, suggesting that patients who expect treatment to be effective tend to engage more constructively in session, which helps bring about symptom reduction. Therapists' expectancies for patient improvement also predicted outcome, although this association was not mediated by the alliance. None of the expectancy scales interacted with alliance ratings in the prediction of clinical improvement.

Adult↗

Dyadic relationship conflict, gender, and mortality in urban hemodialysis patients.

The effects of dyadic satisfaction and conflict have not been well defined in the hemodialysis (HD) population. The aim of this study was to determine whether the perception of decreased dyadic satisfaction was associated with mortality in patients treated with HD, and if so, whether there were different relationships between risk factors, and differential outcomes in men and women. A total of 174 HD patients, primarily African-Americans, involved in dyadic relationships for more than 6 mo had indices of dyadic satisfaction, depression, perception of illness effects, social support, behavioral compliance with the dialysis prescription, and plasma interleukin-1 (IL-1) and beta-endorphin levels measured. Cox proportional hazards models assessed relative mortality risks. Patients' dyadic satisfaction scores correlated with beta-endorphin levels. There was no correlation of IL-1 or beta-endorphin with any psychosocial or behavioral compliance measure in the group as a whole. Correlations between psychosocial, medical, and neuroimmunologic variables were different in men and women. For women, dyadic satisfaction correlated with beta-endorphin levels, depression, and perception of illness. Women with higher dyadic satisfaction and decreased dyadic conflict were at decreased mortality risk, but dyadic adjustment indices were unassociated with differential survival in the larger group of men. Correlations between neuroendocrine and immune markers are different in African-American male and female HD patients. Greater dyadic satisfaction and lower dyadic conflict are independently associated with decreased mortality in female African-American HD patients, of the same order of magnitude as medical risk factors. Such effects may be attributable to a relationship between dyadic satisfaction and conflict and health-related behaviors, or through an effect on neuroendocrine or immunologic status.

Adult↗

Evidence for a deployment-related Gulf War syndrome by factor analysis.

To identify a syndrome unique to Gulf War veterans, the authors applied an exploratory factor analysis to the 47-symptom correlation matrix of 10,423 Gulf War and 8,960 non-Gulf War veteran respondents. A separate factor analysis was performed for Gulf War and non-Gulf War veterans, and the resulting 6 factors were compared between the 2 groups. Five of the factors were very similar in the 2 groups; however, 1 of the factors in the Gulf War group, but not the non-Gulf War group, contained a cluster of symptoms consistent with neurological impairment. Symptoms specific to this factor were blurred vision, loss of balance/dizziness, tremors/shaking, and speech difficulty. The Gulf War veterans who had all of the aforementioned symptoms (n = 277) also reported exposures to several putative risk factors at a rate 3 or more times higher than other Gulf War veterans. This finding suggests a possible syndrome related to Gulf War deployment, which requires objective supporting clinical evidence.

Adult↗