Life Sciences Commons^™

Xk Aprosencephaly And Anencephaly In Sibs, Phillip Townes, Karen Reuter, E. Rosquete, B. Magee

B. Dale Magee

Recent studies have suggested a causal and pathogenetic relationship between holoprosencephaly and anencephaly. In support of the proposed relationship we report a sibship that includes anencephalic male twins and a female infant with a severe form of alobar holoprosencephaly, radial aplasia, and oligodactyly. The upper limb and brain malformations are considered to represent aprosencephaly syndrome. The coexistence of anencephaly and aprosencephaly within a sibship suggests that XK aprosencephaly syndrome may be an autosomal recessive disorder.

Exercise Maintains Sexual Activity In Men Undergoing Androgen Suppression For Prostate Cancer: A Randomized Controlled Trial, Prue Cormie, Robert Newton, Dennis Taaffe, Nigel Spry, David Joseph, M Akhlil Hamid, Daniel Galvao

Prue Cormie

Background:Previous research has shown exercise to be an effective method to mitigate many adverse treatment-related effects of androgen suppression therapy (AST) but the potential impact of exercise on sexual activity remains unknown. The purpose of this investigation was to report the effect of a 12-week exercise program on sexual activity in prostate cancer patients undergoing AST.Methods:Fifty-seven prostate cancer patients undergoing AST were randomly assigned to an exercise program (resistance and aerobic modes; n=29) or usual care control (n=28). Sexual activity was assessed by the European Organization for Research and Treatment of Cancer prostate cancer-specific quality of life questionnaire (QLQ-PR25).Results:QLQ-PR25 data …

Knee Angle-Specific Emg Normalization: The Use Of Polynomial Based Emg-Angle Relationships, J Earp, R Newton, Prue Cormie, A Blazevich

Prue Cormie

The normalization of EMG signals to those recorded during a maximal voluntary contraction provides a valid construct for comparisons of relative muscle activity. However, the length dependence of muscle activation and purported, substantial, muscle translocation and changes in muscle architecture during dynamic movements presents a need for joint angle-dependent normalization processes. The purposes of the present study were to: (1) quantify variations in muscle activity across a large ROM, (2) determine the accuracy with which fitted EMG-joint angle curves accurately characterized these variations, and (3) compare peak (EMG-P) and average (EMG-A) EMG amplitudes obtained during a countermovement leg extension when …

The Capacity To Vote Of Persons With Alzheimer's Disease, Paul Appelbaum, Richard Bonnie, Jason Karlawish

Jason Karlawish

OBJECTIVE: The right to vote can be abrogated when persons become incompetent to cast a ballot. This applies particularly to people with Alzheimer's disease, who at some point will lose capacity. A 2001 federal court decision offered the first clear criteria ("Doe voting capacity standard") for determining voting competence, focused on understanding the nature and effect of voting and on the ability to choose. This article explores how persons with Alzheimer's disease perform on these criteria. METHOD: The Doe standard was operationalized in a brief questionnaire, along with measures of appreciation and reasoning about voting choices. Performance was assessed in …

Beneath The Surface: Discovering The Unvoiced Concerns Of Older Adults With Type 2 Diabetes Mellitus, Jennifer Tjia, Jane Givens, Jason Karlawish, A. Okoli-Umeweni, Frances Barg

Jason Karlawish

Emerging clinical guidelines recommend shared decision making to individualize drug regimens for older adults with Type 2 diabetes mellitus. While the current health education campaign for diabetes in the United States recommends physician-initiated medication-related discussions about adherence and side effects, little emphasis is placed on soliciting patient concerns. This study's aim was to explore the concerns of older adults with diabetes about the complexity of their drug regimens and to determine whether they discussed medication-related concerns with their physician. Twenty-two patients with Type 2 diabetes age 65 years and older who used five or more medications were selected from an …

The Role Of Correctional Officers In Multidisciplinary Mental Health Care In Prisons, Kenneth Appelbaum, James Hickey, Ira Packer

Ira K Packer

Prisons have become the homes of thousands of inmates who have mental disorders. The stress of incarceration can cause morbidity among these individuals, resulting in more severe symptoms and more disruptive behavior. Effective treatment for such inmates often involves services provided by a multidisciplinary treatment team that includes correctional officers. Correctional officers can assist in observations and interventions, and they play a unique role on specialized housing units. Successful collaboration between correctional officers and treatment teams requires a foundation of mutual respect, shared training, and ongoing communication and cooperation. With these elements in place, correctional officers can assist the treatment …

Relationship Between Race And Ethnicity And Forensic Clinical Triage Dispositions, Debra Pinals, Ira Packer, William Fisher, Kristen Roy-Bujnowski

Ira K Packer

OBJECTIVE: Racial and ethnic disparities in the criminal justice system have been widely reported, as have racial and ethnic disparities in diagnoses and certain aspects of clinical management. This study examined the association between race and ethnicity and dispositions for pretrial defendants who were referred for forensic mental health evaluations. METHODS: Available data were reviewed for all defendants in Massachusetts who were referred to a Massachusetts court clinic from 1994 to 2001 for a screening evaluation of their competence to stand trial, their criminal responsibility, or both. Logistic regression models were developed to assess the relationship between defendants' race and …

Use Of A State Inpatient Forensic System Under Managed Mental Health Care, William Fisher, Barbara Dickey, Sharon-Lise Normand, Ira Packer, Albert Grudzinskas, Hocine Azeni

Ira K Packer

OBJECTIVES: One of the goals of managed mental health care has been to lower the use of inpatient psychiatric treatment. In the past, interventions that have limited hospitalization for persons with severe mental illness have led to greater involvement of these individuals with the criminal justice and forensic mental health systems. The authors examined associations between Medicaid managed mental health care in Massachusetts and rates of admission to the inpatient forensic mental health service maintained by the state's mental health department. METHODS: A total of 7,996 persons who were receiving services from the department before and after the introduction of …

Another Armed Cd4(+) T Cell Ready To Battle Hepatocellular Carcinoma, Roniel Cabrera, Gyongyi Szabo

Gyongyi Szabo

No abstract provided.

Human Ezrin-Moesin-Radixin Proteins Modulate Hepatitis C Virus Infection, Terence Bukong, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Host cytoskeletal proteins of the ezrin-moesin-radixin (EMR) family have been shown to modulate single-stranded RNA virus infection through regulating stable microtubule formation. Antibody engagement of CD81, a key receptor for hepatitis C virus (HCV) entry, induces ezrin phosphorylation. Here we tested the role of EMR proteins in regulating HCV infection and explored potential therapeutic targets. We show that HCV E2 protein induces rapid ezrin phosphorylation and its cellular redistribution with F-actin by way of spleen tyrosine kinase (SYK). Therapeutically blocking the functional roles of SYK or F-actin reorganization significantly reduced Huh7.5 cell susceptibility to HCV J6/JFH-1 infection. Using gene regulation, …

Differences In Innate Immune Signaling Between Alcoholic And Non-Alcoholic Steatohepatitis, Jan Petrasek, Timea Csak, Michal Ganz, Gyongyi Szabo

Gyongyi Szabo

The similar histopathological characteristics of alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH), and the crucial role of the innate immune response in both conditions may lead to the assumption that ASH and NASH represent the same pathophysiological entities caused by different risk factors. In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH. Our findings emphasize that ASH and NASH have disease-specific mechanisms and therefore represent distinct biological entities. …

Human Type 2 Myeloid Dendritic Cells Produce Interferon-Lambda And Amplify Interferon-Alpha In Response To Hepatitis C Virus Infection, Shuye Zhang, Karen Kodys, Kui Li, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: The type III interferons (IFN-lambdas: interleukin [IL]-28a, IL-28b, and IL-29) have important roles in hepatitis C virus (HCV) infection, but little is understood about what cells produce these cytokines or how production is activated. We investigated whether human immune cells recognize HCV-infected cells and respond by producing IFN-lambda. METHODS: We cultured healthy human peripheral blood mononuclear cells (PBMCs) with different populations of immune cells and Japanese fulminant hepatitis-1 (JFH-1) HCV-infected Huh7.5 (cell culture-derived HCV particles [HCVcc]/Huh7.5) cells. RESULTS: Human PBMCs recognized HCVcc/Huh7.5 cells and responded by producing IFN-alpha, IFN-gamma, and IFN-lambda. A rare subset of myeloid dendritic …

Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo

Gyongyi Szabo

Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Recent studies demonstrated that Toll-like receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD and NASH. In this review, we emphasize the importance of gut-derived endotoxin and its recognition by TLR4 in the liver. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of individual cell types to the inflammation is …

Serum Dioxins And Polychlorinated Biphenyls Are Associated With Growth Among Russian Boys, Jane Burns, Paige Williams, Oleg Sergeyev, Susan Korrick, Mary Lee, Boris Revich, Larisa Altshul, Julie Del Prato, Olivier Humblet, Donald Patterson, Wayman Turner, Larry Needham, Mikhail Starovoytov, Russ Hauser

Mary M. Lee

OBJECTIVE: We evaluated the associations of serum dioxins and polychlorinated biphenyls (PCBs) with longitudinally assessed growth measurements among peripubertal Russian boys.

METHODS: A total of 499 boys from Chapaevsk, Russia, aged 8 to 9 years were enrolled in the study from 2003 to 2005 and were followed prospectively for 3 years. Blood samples were collected and physical examinations were conducted at entry and repeated at annual study visits. Multivariate mixed-effects regression models for repeated measures were used to examine the associations of serum dioxins and PCBs with longitudinal measurements of BMI, height, and height velocity.

RESULTS: Serum dioxin (total 2005 …

Measurement Of Mullerian Inhibiting Substance Facilitates Management Of Boys With Microphallus And Cryptorchidism, Madhusmita Misra, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a gonadal hormone expressed in a sexually dimorphic pattern. In males, serum MIS reflects Sertoli cell function and provides an estimate of seminiferous tubular integrity. We examined the role of MIS determination in the evaluation of boys with microphallus (n = 62) and/or cryptorchidism (n = 156). MIS was normal in 69.2% of boys with isolated microphallus compared with 38.1% of boys with microphallus and coexisting cryptorchidism (P < 0.05). In the cryptorchid group, MIS was normal in 46.8%, low in 24.4%, and absent in 28.8%. Normal values for age were associated with testicular tissue, whereas …

Evaluation Of Short And Tall Stature In Children, Benjamin Nwosu, Mary Lee

Mary M. Lee

Children and adolescents whose heights and growth velocities deviate from the normal percentiles on standard growth charts present a special challenge to physicians. Height that is less than the 3rd percentile or greater than the 97th percentile is deemed short or tall stature, respectively. A growth velocity outside the 25th to 75th percentile range may be considered abnormal. Serial height measurements over time documented on a growth chart are key in identifying abnormal growth. Short or tall stature is usually caused by variants of a normal growth pattern, although some patients may have serious underlying pathologies. A comprehensive history and …

Augmented Growth Hormone (Gh) Secretory Burst Frequency And Amplitude Mediate Enhanced Gh Secretion During A Two-Day Fast In Normal Men, Mark Hartman, Johannes Veldhuis, Michael Johnson, Mary Lee, K. Alberti, Eugene Samojlik, Michael Thorner

Mary M. Lee

Serum GH concentrations are increased in fasted or malnourished human subjects. We investigated the dynamic mechanisms underlying this phenomenon in nine normal men by analyzing serum GH concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the second day of a fast with a multiple-parameter deconvolution method to simultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 5-fold increase in the 24-h endogenous GH production rate [78 +/- 12 vs. 371 +/- 57 micrograms/Lv (Lv, liter of distribution volume) or 0.24 +/- 0.038 vs. 1.1 +/- …

Male Pubertal Development: Are Endocrine-Disrupting Compounds Shifting The Norms, William Zawatski, Mary Lee

Mary M. Lee

Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that interfere with endogenous endocrine action. The frequent use of chemicals with endocrine active properties in household products and contamination of soil, water, and food sources by persistent chemical pollutants result in ubiquitous exposures. Wildlife observations and animal toxicological studies reveal adverse effects of EDCs on reproductive health. In humans, a growing number of epidemiological studies report an association with altered pubertal timing and progression. While these data are primarily reported in females, this review will focus on the small number of studies performed in males that report an association of polychlorinated …

Transient Hyperthyroidism In An Adolescent With Hydatidiform Mole, Madhusmita Misra, Lynne Levitsky, Mary Lee

Mary M. Lee

No abstract provided.

Mullerian Inhibiting Substance In Humans: Normal Levels From Infancy To Adulthood, Mary Lee, Patricia Donahoe, Tomonobu Hasegawa, Bernard Silverman, Gretchen Crist, Sharon Best, Yukihiro Hasegawa, Richard Noto, David Schoenfeld, David Maclaughlin

Mary M. Lee

Mullerian-inhibiting substance (MIS) is a gonadal hormone synthesized by Sertoli cells of the testis and granulosa cells of the ovary. To facilitate the use of MIS for the evaluation of intersex disorders and as a tumor marker in women with MIS-expressing ovarian tumors, we measured MIS in 600 serum samples from males and females. These data show that mean MIS values for males rise rapidly during the first year of life and are highest during late infancy, then gradually decline until puberty. In contrast, MIS values in females are lowest at birth and exhibit a minimal increase throughout the prepubertal …

Serum Concentrations Of Organochlorine Pesticides And Growth Among Russian Boys, Jane Burns, Paige Williams, Oleg Sergeyev, Susan Korrick, Mary Lee, Boris Revich, Larisa Altshul, Julie Del Prato, Olivier Humblet, Donald Patterson, Wayman Turner, Mikhail Starovoytov, Russ Hauser

Mary M. Lee

BACKGROUND: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. OBJECTIVE: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. METHODS: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and …

Mullerian Inhibiting Substance In The Diagnosis And Management Of Intersex And Gonadal Abnormalities, Michael Gustafson, Mary Lee, Lara Asmundson, David Maclaughlin, Patricia Donahoe

Mary M. Lee

Mullerian inhibiting substance (MIS), a gonadal hormone important in sexual differentiation, is high (10 to 70 ng/mL) in human male serum postnatally for several years before declining during the peripubertal period, but is undetectable in female serum until the onset of puberty. The sexually dimorphic secretion of MIS suggested possibilities for its use in several clinical settings. Thirty-one patients with intersex and gonadal anomalies from 17 institutions were therefore evaluated between 1989 and 1992 with an MIS enzyme-linked immunosorbent assay (ELISA). Serum MIS levels correlated with the presence of testicular tissue in two patients with suspected anorchia, five patients with …

Campylobacter Meningitis In Childhood, Mary Lee, Robert Welliver, Leonard La Scolea

Mary M. Lee

No abstract provided.

Predictors Of Serum Dioxin, Furan, And Pcb Concentrations Among Women From Chapaevsk, Russia, Olivier Humblet, Paige Williams, Susan Korrick, Oleg Sergeyev, Claude Emond, Linda Birnbaum, Jane Burns, Larisa Altshul, Donald Patterson, Wayman Turner, Mary Lee, Boris Revich, Russ Hauser

Mary M. Lee

Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total …

Mentoring Fathers Of Children Newly Diagnosed With T1dm, Susan Sullivan-Bolyai, Carol Bova, Mary Lee, Philip Gruppuso

Mary M. Lee

PURPOSE: To pilot test a social support intervention for fathers of children (T1DM).

DESIGN AND METHODS: The pilot study was part of a larger randomized, controlled clinical trial. Father participants (28 fathers of children newly diagnosed) were recruited from two pediatric diabetes centers. For 12 months fathers (n = 19) and their spouses in the experimental arm received social support (home visits and phone calls). Control group fathers (n = 9) and their spouses received the phone number of an experienced parent (but not formally educated to provide social support) to call as needed.

RESULTS: Fathers in the intervention group …

Key Factors In The Regulation Of Fetal And Postnatal Leydig Cell Development, Xiufeng Wu, Shengqin Wan, Mary Lee

Mary M. Lee

The primary function of testicular Leydig cells is the production of androgens to promote sexual differentiation in the fetus, secondary sexual maturation at puberty, and spermatogenesis in the adult. The fetal and postnatal (adult) populations of Leydig cells differ morphologically and have distinct profiles of gene expression. As postnatal Leydig cells differentiate, they transition through three discrete maturational stages characterized by decreasing proliferative rate and increasing testosterone biosynthetic capacity. In this review, we discuss the development of both fetal and postnatal Leydig cells and review the regulation of this process by some of the key hormones and growth factors.

Consensus Statement On The Use Of Gonadotropin-Releasing Hormone Analogs In Children, Jean-Claude Carel, Erica Eugster, Alan Rogol, Lucia Ghizzoni, Mark Palmert, Mary Lee

Mary M. Lee

OBJECTIVE: Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. PARTICIPANTS: When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe, an equal male/female ratio, and a balanced spectrum of professional seniority and expertise. EVIDENCE: Preference was given to articles written in English with long-term …

The Role Of Mullerian Inhibiting Substance In The Evaluation Of Phenotypic Female Patients With Mild Degrees Of Virilization, Madhusmita Misra, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a sexually dimorphic gonadal hormone with proven efficacy in the evaluation of boys with cryptorchidism and children with intersex conditions. We examined the role of MIS determination in the evaluation of 65 phenotypic females with mild virilization. Among the 28 subjects with MIS values elevated above the normal female range, all had abnormal gonadal tissue: ovotestes in 11, testes in 7, dysgenetic gonads in 7, and MIS-secreting ovarian tumors in 3. Among the 37 children with serum MIS in the normal female range, 19 had detectable MIS and 18 had unmeasurable MIS. In the former …

The Influence Of Endocrine Disruptors On Pubertal Timing, Elka Jacobson-Dickman, Mary Lee

Mary M. Lee

PURPOSE OF REVIEW: Overview of the effects of endocrine disruptors on pubertal timing. RECENT FINDINGS: Epidemiologic studies in humans support animal data demonstrating that exposures to endocrine-disrupting compounds have pronounced effects on pubertal timing and that the timing of endocrine-disrupting compound exposure and the specific agent causes different outcomes. Recent studies confirm subtle effects of lead, dioxins, and phytoestrogens on delaying onset of puberty and demonstrate an association of phthalates and polychlorinated biphenyls with earlier breast development and menarche, respectively. These studies, however, are complicated by mixed exposures of compounds which individually may have opposing actions on the reproductive axis. …

Alterations In The Pulsatile Mode Of Growth Hormone Release In Men And Women With Insulin-Dependent Diabetes Mellitus, Christopher Asplin, Amilton Faria, Elizabeth Carlsen, Veronica Vaccaro, Richard Barr, Ali Iranmanesh, Mary Lee, Johannes Veldhuis, William Evans

Mary M. Lee

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion timeseries analysis. Compared to those in age-matched controls, …