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Biomedical subjects

J Goldberg

Publications and source records attributed to J Goldberg.

At least 145 records · Page 8Linked to original sources

Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I.

The crystal structure of calcium/calmodulin-dependent protein kinase I has been determined in the autoinhibited form. The C-terminal regulatory region of the enzyme forms a helix-loop-helix segment that extends across the two domains of the catalytic core, making multiple inhibitory interactions. Elements of the first regulatory alpha helix and the loop interfere with the binding site for peptide substrates, while the loop and the second helix interact with the ATP-binding domain to induce conformational changes that obstruct the nucleotide binding pocket. One part of the calmodulin recognition element protrudes away from the catalytic domain and is potentially available for an initial interaction with calmodulin. The structure provides a view of an intact calmodulin target and suggests that substantial structural changes will accompany kinase activation by calmodulin binding to the regulatory region.

Adenosine Triphosphate↗

Univariate analysis of dichotomous or ordinal data from twin pairs: a simulation study comparing structural equation modeling and logistic regression.

The univariate analysis of categorical twin data can be performed using either structural equation modeling (SEM) or logistic regression. This paper presents a comparison between these two methods using a simulation study. Dichotomous and ordinal (three category) twin data are simulated under two different sample sizes (1,000 and 2,000 twin pairs) and according to different additive genetic and common environmental models of phenotypic variation. The two methods are found to be generally comparable in their ability to detect a "correct" model under the specifications of the simulation. Both methods lack power to detect the right model for dichotomous data when the additive genetic effect is low (between 10 and 20%) or medium (between 30 and 40%); the ordinal data simulations produce similar results except for the additive genetic model with medium or high heritability. Neither method could adequately detect a correct model that included a modest common environmental effect (20%) even when the additive genetic effect was large and the sample size included 2,000 twin pairs. The SEM method was found to have better power than logistic regression when there is a medium (30%) or high (50%) additive genetic effect and a modest common environmental effect. Conversely, logistic regression performed better than SEM in correctly detecting additive genetic effects with simulated ordinal data (for both 1,000 and 2,000 pairs) that did not contain modest common environmental effects; in this case the SEM method incorrectly detected a common environmental effect that was not present.

Analysis of Variance↗

Cycle of abuse and psychopathology in cleric and noncleric molesters of children and adolescents.

Sexual abuse in childhood is frequently reported among sex offenders and has been hypothesized to be one of a number of psychological factors etiologically related to perpetration of child molestation in adulthood. In the current study we examine a sample of cleric and noncleric admitted child molesters and normal control subjects in their exposure to sexual abuse in childhood and current psychopathology. Odds ratios for the association between exposure to sexual abuse and child molestation were obtained while adjusting for group differences in demographic and psychological characteristics. Results indicated exposure to sexual abuse in childhood was associated with becoming a child molester for both cleric and noncleric offenders (p < .0002). Nonclerics indicated more severe psychopathology than clerics. Sexual abuse in childhood is one of many risk factors for becoming a perpetrator of child molestation in adulthood for both cleric and noncleric child molesters. Noncleric offenders demonstrated more sociopathy and mental disorder in general while cleric offenders indicated more sexual conflictedness, suggesting different psychoetiologies of offending among cleric and noncleric child molesters.

Adolescent↗

Preferences for intracytoplasmic sperm injection versus donor insemination in severe male factor infertility: a preliminary report.

With the advent of intracytoplasmic sperm injection (ICSI), our programme noted a drop in the number of couples using donor insemination (DI) for severe male factor infertility. Over the first 8 months in which our infertility programme offered both treatments, 27 consecutive couples scheduled for ICSI and 15 consecutive couples scheduled for DI were evaluated Since all patients in our infertility programme beginning in-vitro fertilization (IVF) with planned ICSI or starting DI undergo a semi-structured psychological interview, the psychologist's clinical notes as well as the medical chart were reviewed and coded retrospectively to determine factors related to a couple's treatment choice. Couples who chose IVF-ICSI over DI had a higher occupational status and included husbands with higher educational levels. Their most common motivation was to have the husband's biological child (93% of couples in the ICSI group). The most common motivation for choosing DI (60% of DI couples) was that IVF was not financially affordable. Choice of treatment was not related to psychological adjustment, the husband having prior biological children, or his risk of passing on a genetic defect to offspring. These preliminary data raise the concern that, with the success of ICSI, DI may change in the USA from being an option dictated by semen quality to a second choice treatment utilized for economic reasons.

Adult↗

The association of antisocial personality symptoms with marijuana abuse/dependence. A monozygotic co-twin control study.

This study examines the association of symptoms of lifetime antisocial personality disorder (ASP) with marijuana abuse/dependence in Vietnam-era veteran male monozygotic twin pairs. In 1992, 1,874 monozygotic twin pairs responded to a structured psychiatric interview that obtained data on lifetime history of drug use and ASP. Among randomly selected individuals from each twin pair, 8 of 10 ASP symptoms were significantly more prevalent in persons with a lifetime history of marijuana abuse/dependence compared with those who had never abused any drug (p < .001). Among 99 marijuana discordant twin pairs, however, only two ASP symptoms, "failure to conform to social norms" (odds ratio, 2.8; 95% confidence interval, 1.5 to 5.5) and "reckless regard of own or other's personal safety" (odds ratio, 2.4; 95% confidence interval, 1.0 to 5.4) were significantly increased in marijuana abusing/dependent twins compared with their non-abusing/nondependent twin brother. After adjustment for conduct disorder, alcohol abuse/dependence, and exposure to combat in Vietnam, only "failure to conform to social norms of lawful behavior" (odds ratio, 2.42; 95% confidence interval, 1.12 to 5.21) remained significantly increased in twins with marijuana abuse/dependence.

Antisocial Personality Disorder↗

Models of treatment seeking for alcoholism: the role of genes and environment.

We investigated the relative influence of genes and environment on the decision to seek treatment for alcoholism under three models of health care utilization. Lifetime alcohol dependence and two measures of treatment seeking for alcohol problems were determined from a 1992 telephone administration of the Diagnostic interview Schedule. Data were analyzed from 1,864 monozygotic and 1,492 dizygotic male twin respondents from the Vietnam Era Twin Registry. Genetic and environmental contributions to the decision to seek treatment for alcoholism were assessed under competing models for the relationship between genetic influences on alcoholism risk and genetic influences on treatment seeking among those who became alcoholics. Under the best-fitting model, genetic influence accounted for 41% of the variance in treatment seeking and 55% of the liability for alcoholism. Shared environment explained none of the variance in liability for alcoholism, but 40% of the variance in treatment seeking. The severity of alcoholism alone is an inadequate model of treatment seeking, because decisions to seek alcohol treatment are also influenced by substantial genetic and or shared environmental factors unrelated to the determinants of alcoholism.

Adult↗

Burnout and its correlates in emergency physicians: four years' experience with a wellness booth.

OBJECTIVE: To measure the degree of burnout among emergency physicians (EPs) and to identify and rank predictive factors. METHODS: Using the Maslach Burnout Inventory as well as a 79-item questionnaire, a cross-sectional survey was conducted for physician registrants at the Annual Scientific Assemblies of the American College of Emergency Physicians from 1992 to 1995. Degrees of burnout were stratified into low, moderate, and high ranges. Univariate and stepwise multiple regression analyses were conducted to identify and rank correlates to burnout scores. RESULTS: Of 1,272 registrants taking the inventory, 60% registered in the moderate to high burnout ranges. Twenty-one correlates were identified. These were classified broadly in terms of negative perceptions of self, negative practice habits and attitudes, and unhealthy lifestyles. The most highly ranked correlates were: self-recognition of burnout, lack of job involvement, negative self-assessment of productivity, dissatisfaction with career, sleep disturbances, increased number of shifts per month, dissatisfaction with specialty services, intent to leave the practice within 10 years, higher levels of alcohol consumption, and lower levels of exercise. Age and years of practice were not significant predictors of burnout. Projected attrition rates were 7.5% over 5 years and 25% over 10 years. CONCLUSIONS: Elevated levels of burnout exist among a substantial percentage of surveyed EPs. However, there is evidence for a "survivor" category of practitioners for whom burnout either does not develop or is a reversible process. The projected attrition rate over 5 and 10 years appears to be no greater than that of the average medical specialty.

Adaptation, Psychological↗

Stimulation of cilia beat frequency by serotonin is mediated by a Ca2+ influx in ciliated cells of Helisoma trivolvis embryos

Serotonin (5-HT) has been established as a regulator of ciliary beating in numerous systems. In early embryos of Helisoma trivolvis, a cilia-driven rotational movement is modulated by the release of endogenous serotonin from a pair of embryonic neurons, ENC1s, directly onto the ciliated epithelium. The present study was undertaken to examine the signal transduction mechanisms underlying serotonin-mediated cilio-excitation in Helisoma trivolvis embryos. Using time-lapse videomicroscopy, the ciliary beat frequency (CBF) of cultured embryonic ciliated cells was measured in response to various pharmacological manipulations. Serotonin increased CBF in a dose-dependent manner. Addition of 8-bromo-cyclic AMP, isobutylmethylxanthine (IBMX) or a combination of forskolin and IBMX, treatments that elevate the concentration of intracellular cyclic AMP, did not mimic the serotonin-induced increase in CBF. Thus, cyclic AMP does not appear to be involved in the regulation of CBF in this system. In contrast, depolarizing the cells with KCl or veratridine, and artificially raising the intracellular Ca2+ concentration with thapsigargin or A23187, caused a serotonin-like increase in CBF. Furthermore, the serotonin response was abolished in a Ca2+-depleted medium or in a medium containing the L-type Ca2+ channel blockers verapamil or nifedipine. These results suggest that serotonin-stimulated cilio-excitation in cultured Helisoma trivolvis cells involves an influx of Ca2+ to increase intracellular Ca2+ concentration. The link between serotonin-receptor binding and Ca2+ influx in these cells has yet to be determined.

Journal Article↗

The expanded racial and ethnic codes in the Medicare data files: their completeness of coverage and accuracy.

OBJECTIVES: This paper evaluates the new race/ethnicity codes for Asian Americans, Hispanics, and Native Americans that have recently been added to the Medicare enrollment database. METHODS: The race/ethnicity code revisions made by the Health Care Financing Administration are described and evaluated by (1) comparing the numbers of persons identified as Asian Americans, Hispanics, and Native Americans with corresponding population census projections and (2) determining whether Medicare enrollees born in Asian and Hispanic countries are assigned Asian and Hispanic codes. RESULTS: Among persons 65 years of age and older, approximately 24% of Hispanics, 17% of Native Americans, and 56% of Asian Americans are identifiable by the new codes. From 18% to 29% of enrollees 65 years old or older born in Mexico, Puerto Rico, and Cuba are coded as Hispanic, and from 14% to 73% of enrollees born in nine Asian countries are classified as Asian American. Classification is not random but is related to timing of migration and to country of origin. CONCLUSIONS: Researchers should resist the temptation to base analyses on the revised Health Care Financing Administration race/ethnicity codes, since coverage is incomplete and biased.

Adolescent↗

[Urinary flow in children: correlation with age, body height and body surface area].

Peak flow rate data (Qmax) are important for diagnosis of lower urinary tract obstruction. However, the lack of uroflowmetry studies in children, makes their interpretation difficult. With this aim, we studied 167 boys classified in four groups according to their age (G1: n = 48, 6-7 years; G2: n = 43, 8-9 years; G3: n = 37, 10-11 years; G4: n = 39, 12-14 years). We studied in all children, weight, height, body surface area, peak flow rate (Qmax) and the correspondant urinary volume (Vol). Means and standard deviations of Qmax (ml/sec) were: 15 +/- 5 (G1), 15 +/- 5 (G2), 17 +/- 5 (G3) and 22 +/- 7 (G4) respectively. Corresponding urinary volumes (Vol) (mean standard deviation-in ml) were: G1 = 123 +/- 75; G2 = 122 +/- 79; G3 = 158 +/- 96 and G4 = 162 +/- 101. We found a significant correlation (p < 0,01) between Qmax and Vol in groups G2, G3 and G4; and between Qmax and height in groups G1 and G4. The authors demonstrated a positive correlation between maximum flow and voided volume, and an increase of Qmax with age.

Adolescent↗

Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the Western Electric Study.

Dietary factors are likely candidates for important determinants of prostatic cancer risk. Among the most investigated nutritional factors have been antioxidants. We evaluated dietary beta-carotene and vitamin C in relation to subsequent risk of prostate cancer in a prospective study of 1,899 middle-aged men. We combined prostate cancer cases diagnosed in the first 24 years of follow-up with incident cases identified from the Health Care Financing Administration hospitalization and outpatient files during an additional 6-year follow-up period. We obtained death certificates for all decedents. During the 30-year follow-up, prostate cancer developed in 132 men. There was no indication that consumption of beta-carotene or vitamin C was related to increased or decreased risk of prostate cancer. Relative risks for highest vs lowest quartiles of beta-carotene and vitamin C intake were 1.27 [95% confidence interval (CI) = 0.75-2.14] and 1.03 (95% CI = 0.59-1.60), respectively, after adjustment for age, number of cigarettes smoked per day, dietary cholesterol and saturated fat, alcohol consumption, total energy intake, and occupation. Associations between intake of these nutrients and risk of prostate cancer differed depending on whether the cancer was diagnosed during the first 19 years of follow-up or the next 11 years of follow-up. Overall survival over the 30 years of follow-up was positively associated with intake of beta-carotene and vitamin C.

Adult↗

Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1.

The crystal structure of mammalian protein phosphatase-1, complexed with the toxin microcystin and determined at 2.1 A resolution, reveals that it is a metalloenzyme unrelated in architecture to the tyrosine phosphatases. Two metal ions are positioned by a central beta-alpha-beta-alpha-beta scaffold at the active site, from which emanate three surface grooves that are potential binding sites for substrates and inhibitors. The carboxy terminus is positioned at the end of one of the grooves such that regulatory sequences following the domain might modulate function. The fold of the catalytic domain is expected to be closely preserved in protein phosphatases 2A and 2B (calcineurin).

Amino Acid Sequence↗

Mortality ascertainment in the veteran population: alternatives to the National Death Index.

Veterans of the US military service constitute a dynamic cohort that is suitable for epidemiologic investigations. However, the ability to ascertain vital status is paramount to the value of this population in studies having mortality as a primary endpoint. The purpose of this study was to estimate and compare the mortality ascertainment obtained from the Department of Veterans Affairs Patient Treatment File and Beneficiary Identification and Record Locator System (BIRLS) with that obtained from the National Death Index on a cohort of 17,118 male veterans hospitalized in 1970 or 1971. Based on the 4,246 deaths identified in this cohort between 1979 and 1988, the sensitivities of BIRLS, the Patient Treatment File, and the National Death Index were 94.5%, 33.0%, and 96.7%, respectively. BIRLS was comparable with the National Death Index regarding mortality ascertainment and allowed for central acquisition of 89% of the death certificates from the Department of Veterans Benefits. There was no difference detected in the completeness of the BIRLS file before and after passage of the Omnibus Act in 1981. The Patient Treatment File served as a complement to BIRLS, providing additional mortality data and identification of hospitals for recall of medical records. The National Death Index provided the best mortality ascertainment, but acquistion of death certificates from individual states was extremely time consuming and expensive. The authors recommend greater consideration by investigators of sampling the veteran population and utilizing available Veterans Affairs databases for large studies in which mortality is the primary endpoint of interest.

Adult↗

Differential heritability of adult and juvenile antisocial traits.

BACKGROUND: Studies of adult antisocial behavior or criminality usually find genetic factors to be more important than the family environment, whereas studies of delinquency find the family environment to be more important. We compared DSM-III-R antisocial personality disorder symptoms before vs after the age of 15 years within a sample of twins, rather than comparing across studies. METHODS: We administered the Diagnostic Interview Schedule Version III-revised by telephone to 3226 pairs of male twins from the Vietnam Era Twin Registry. Biometrical modeling was applied to each symptom of antisocial personality disorder and summary measures of juvenile and adult symptoms. RESULTS: Five juvenile symptoms were significantly heritable, and five were significantly influenced by the shared environment. Eight adult symptoms were significantly heritable, and one was significantly influenced by the shared environment. The shared environment explained about six times more variance in juvenile anti-social traits than in adult traits. Shared environmental influences on adult antisocial traits overlapped entirely with those on juvenile traits. Additive genetic factors explained about six times more variance in adult vs juvenile traits. The juvenile genetic determinants overlapped completely with genetic influences on adult traits. The unique environment (plus measurement error) explained the largest proportion of variance in both juvenile and adult antisocial traits. CONCLUSIONS: Characteristics of the shared or family environment that promote antisocial behavior during childhood and early adolescence also promote later antisocial behavior, but to a much lesser extent. Genetic causal factors are much more prominent for adult than for juvenile antisocial traits.

Adolescent↗

Thoracic spinal nerve and root conduction: a magnetic stimulation study.

We describe a technique of magnetic coil (MC) stimulation of the thoracic spinal nerves and roots in 12 normal subjects and a patient with diabetes mellitus. We kept the MC flat against the vertebral column in the midline over T-7, T-8, and T-9 spinous processes and obtained compound muscle action potentials from the upper rectus abdominis, external oblique, and intercostal muscles. We obtained mean latencies to these muscles after stimulation in the posterior axillary line. We noted that the onset latencies remained fixed despite increasing the intensity of stimulation from 30% to 100% and on moving the coil up to 3 cm lateral to the spinous processes suggesting that the stimulation of the fastest conducting fibers was occurring at a fixed site, most likely at the intervertebral foramina. Prolonged latencies in the diabetic patient confirmed the diagnosis of radiculoneuropathy.

Adult↗