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Biomedical subjects

J F Feldman

Publications and source records attributed to J F Feldman.

At least 19 recordsLinked to original sources
PubMed1997

Analysis of frequency (frq) clock gene homologs: evidence for a helix-turn-helix transcription factor.

The frq gene plays a key role in the organization of the Neurospora crassa circadian clock. Our previous analysis of a C-terminal fragment of the putative FRQ protein suggested it is a nuclear transcription factor but did not identify a known DNA-binding domain. If the hypothesis is correct that FRQ is a transcription factor, sequences consistent with this function should be conserved in distantly related species. To investigate, we have cloned frq homologs from other filamentous fungi including Chromocrea spinulosa, and Leptosphaeria australiensis. Alignment of the Leptosphaeria and Chromocrea proteins with the published (complete) sequences for Neurospora crassa and Sordaria fimicola shows that they are respectively about 47%, and 43%, identical to both Neurospora and Sordaria. The alignment identifies several short regions of high conservation punctuated by regions showing near total divergence. Sequences consistent with FRQ being a transcription factor are generally conserved. Most importantly, we show that a highly conserved segment of the protein has strongly predicted helix-turn-helix (HTH) structure as supported by three independent methods. Further, this segment shows the defining sequence characteristics of known HTH DNA-binding domains. Amino acids at positions altered in frq mutant alleles are conserved in all species examined. Transformation of the Neurospora frq9 (conditionally arrhythmic) mutant with the Chromocrea homolog rescued the pigmentation and conidiation defects of the mutant but not the circadian defect; the Leptosphaeria homolog failed to rescue any defect. Together, these data provide the first testable hypotheses concerning several specific aspects of FRQ structure and function.

Amino Acid Sequence↗
PubMed1996

Evolution of the frequency (frq) clock locus in Ascomycete fungi.

The frequency (frq) locus of Neurospora crassa plays a key role in the organization of circadian rhythms. Similar timing systems have been found in nearly all eukaryotes as well as some prokaryotes; thus, frq may be an excellent gene with which to conduct evolutionary studies. To investigate, we used the cloned frq locus from ascomycete fungi representing two classical taxonomic classes and three orders to examine two open questions in ascomycete evolution. Class Pyrenomycetidae is represented by several species of Neurospora, Sordaria fimicola, and Chromocrea spinulosa; class Loculoascomycetidae is represented by the marine fungus Leptosphaeria australiensis. Generation of detailed restriction maps of homologs from the Neurospora species allows analysis of evolutionary relationships among these closely related species. A maximum-parsimony tree based on these restriction data suggests that Neurospora tetrasperma groups more closely with Neurospora sitophila than with Neurospora crassa using the homothallic species Neurospora galapagosensis as an outgroup. A maximum-parsimony tree derived using amino acid sequences from Neurospora crassa, Sordaria fimicola, Chromocrea spinulosa, and Leptosphaeria australiensis surprisingly suggests that Leptosphaeria austral should be classified within Pyrenomycetes rather than in a separate class. This suggestion is based on the observations that Leptosphaeria groups with Chromocrea on an evolutionary tree, is more closely related to Neurospora and Sordaria than is Chromocrea, and shares a conserved intron with Chromocrea. Together, these data show that frq is a useful gene with which to conduct evolutionary studies.

Amino Acid Sequence↗
PubMed1996

Neonatal cranial ultrasound abnormalities in low birth weight infants: relation to cognitive outcomes at six years of age.

OBJECTIVE: To assess the independent relation of neonatal cranial ultrasound (US) abnormalities in low birth weight (LBW) infants to cognitive outcomes at 6 years of age. DESIGN: Prospective cohort study. SAMPLE AND METHODS: Six-year follow-up data were obtained on a regional birth cohort of LBW infants (< 2 kg) systematically screened as neonates with serial US. US abnormalities were dichotomized into isolated germinal matrix/intraventricular hemorrhage (GM/IVH) and parenchymal lesions/ventricular enlargement (PL/VE). Global cognitive outcomes (mental retardation, borderline intelligence, and normal intelligence) and selected specific cognitive abilities were assessed at 6 years of age with standardized instruments. Multivariate techniques were used to assess the effects of US independent of maternal social disadvantage at birth and other perinatal and neonatal risk factors. RESULTS: The sample as a whole had a significantly elevated rate of mental retardation (MR; 5%), almost all moderate to profound in severity. PL/VE was independently related to MR (odds ratio [OR], 65.8; confidence interval [CI], 19.1 to 22.4) and borderline intelligence (OR, 3.7; CI, 1.3 to 10.8); isolated GM/IVH was more modestly related to MR (OR, 4.6; CI, 1.2 to 18.6) but not related to borderline intelligence. Approximately half of the cases of MR were attributable to PL/VE independent of other factors. Of non-US factors, the number of days receiving mechanical ventilation increased the risk for MR. Maternal social disadvantage increased the risk for borderline intelligence but not MR. Among children of normal intelligence, those with PL/VE, but not isolated GM/IVH, performed more poorly than those without US abnormalities on tests of visual perceptual organization but not on tests of language, memory, or quantitative skills. CONCLUSION: Prevention of white matter injury would substantially improve cognitive outcomes for LBW infants.

Aging↗
PubMed1996

Memory and processing speed in preterm children at eleven years: a comparison with full-terms.

This study examined the effects of prematurity on 11-year-olds' performance on 2 specific aspects of cognition--memory and processing speed, using a new computer-administered battery, the Cognitive Abilities Test (CAT: Detterman). Preterms performed more poorly than their full-term controls on all memory tasks; this relative deficit was associated with the presence and severity of neonatal Respiratory Distress Syndrome (RDS). Preterms were also slower on selected aspects of processing speed but not on motor speed. Memory and processing speed, taken together, accounted for much of the 10-point difference in WISC-R IQ between groups.

Birth Weight↗
PubMed1994

Psychiatric morbidity in school-age children with congenital human immunodeficiency virus infection: a pilot study.

This study examined the relationship between human immunodeficiency virus (HIV) infection and psychiatric morbidity within the context of prenatal drug exposure. Twenty-six HIV-infected, 14 seroreverted, and 20 control (non-HIV-exposed) children were studied; the sample consisted of nonreferred children living in foster placement who had been exposed to maternal drug addiction. Each child received a psychiatric diagnostic evaluation which included completion by the caretaker of a structured diagnostic interview and a behavior checklist on the child as well as a child self-report on a pictorial interview. Age, ethnicity, and IQ were controlled in the analyses because of group differences. There were high rates of behavioral and psychiatric morbidity, especially with respect to disruptive behavior disorders, in this sample of school-age children with HIV infection, but similarly high rates were found in the seroreverted and non-HIV-exposed children. There was some suggestion that the HIV-infected children were experiencing higher levels of subjective distress than either the nonexposed or seroreverted children. The possible relevance of drug exposure to the behavioral outcomes observed here is discussed, as well as the importance of using age-appropriate materials to elicit subjective distress in HIV-infected school-age children. Clinical implications and directions for further research are discussed.

Anxiety↗
PubMed1992

Infant information processing in relation to six-year cognitive outcomes.

As part of a longitudinal follow-up of full-terms and preterms, infant measures of information processing obtained at 7 months and 1 year were related to various 6-year outcomes: general intelligence, language proficiency, early reading and quantitative skills, and several facets of perceptual organization (N = 91). 7-month Visual recognition memory (VRM) was associated with 6-year performance in all domains, and 3 1-year measures--VRM, cross-modal transfer (CMT), and object permanence--were related to IQ and/or one or more specific outcomes (r's = .20 to .47). Many of the infant-childhood relations remain significant even with IQ partialed. Additionally, 7-month VRM and 1-year CMT scores were lower for infants who, at 6 years, were considered at risk for learning disabilities. Overall, measures from the first year of life predicted both specific cognitive abilities and IQ at 6 years; to some extent, the specific abilities were predicted independently of IQ.

Achievement↗
PubMed1989

The development of gender-related behavior in females following prenatal exposure to diethylstilbestrol (DES).

Animal research has shown that diethylstilbestrol (DES) present during the sensitive developmental periods of the hypothalamus and adjacent areas of the brain affects the development of sex-dimorphic brain structures and subsequent behavior. To test for corresponding behavioral effects in humans, 30 women with a history of prenatal DES exposure were contrasted with 30 unexposed women who had been referred to the same clinic for a colposcopic examination because of an abnormal Pap smear. Gender-role behavior of childhood, adolescence, and adulthood was assessed by means of a semistructured interview, the Gender Role Assessment Schedule-Adult, and the Bem Sex Role Inventory. The mothers of these women were interviewed about their daughters with the "mother form" of the same interview schedule. The results suggest that DES women show less orientation toward parenting than the controls. There were no consistent group differences in other domains of gender-role behavior.

Adolescent↗
PubMed1988

On the role of protein synthesis in the circadian clock of Neurospora crassa.

Inhibitors of protein synthesis reset the biological clocks of many organisms. This has been interpreted to mean either that the synthesis per se of proteins is a step in the oscillatory feedback loop or merely that certain unstable protein(s) are required at certain times of the cycle to complete the feedback loop. We report here that Neurospora strains bearing the clock mutation frq-7 are relatively insensitive to the resetting action of the protein-synthesis-inhibitor cycloheximide. Protein synthesis itself in this mutant is inhibited by the drug to the same extent as in wild type. Since the clock of frq-7 continues to run relatively unimpeded even in the virtual absence of protein synthesis, it is unlikely that synthesis per se can be a part of the feedback cycle. Rather, we suggest that for normal operation of the Neurospora clock, certain protein(s) with a high turnover rate are required daily and, thus, must be resynthesized each day (at least) during discrete times in the cycle. The frq-7 mutation simultaneously alters several distinct clock characteristics--period length, temperature compensation, and resetting by cycloheximide. A model is presented to unify these observations.

Circadian Rhythm↗
PubMed1988

Perinatal factors in the development of gender-related play behavior: sex hormones versus pregnancy complications.

This report addresses the question of biological factors that may contribute to the development of gender-typical and gender-atypical play behavior. In lower mammals, sex differences in juvenile behavior are to a considerable extent determined by organizational effects of prenatal or perinatal androgenic hormones. Birke and Sadler (1983) showed that not only perinatal androgens but also progestogens such as medroxyprogesterone acetate (MPA) affect (in this case: demasculinize) the play behavior of both sexes in the rat. Here, we report on a study of sex-dimorphic play behavior of children born from pregnancies that were treated with various sex hormones. The Child Game Participation Questionnaire (Bates and Bentler 1973) was administered to 13 boys and 15 girls prenatally exposed to MPA, 22 boys and 15 girls exposed to a variety of synthetic progestogens or estrogens singly or in combination, and to pair-matched control subjects, all between 8 and 14 years old. Pregnancy complications were assessed by two scores, 1) "Pregnancy Complications Summary Score (excluding bleeding)," 2) "Vaginal Bleeding During Pregnancy." The results of paired t-tests showed a number of hypomasculinization effects for the hormone-exposed groups. Controlling for the effects of pregnancy complications and age at study by exploratory hierarchical multiple regression analysis indicated that these variables did not account for the hormone-exposure effects. Our results provide further evidence that prenatal hormones influence the sex-dimorphic play behavior of human children in the same direction as that of other mammals.

Child↗
PubMed1988

Individual differences in infants' information processing: reliability, stability, and prediction.

A group of 46 full-term and 54 high-risk preterm (less than 1,500 grams birthweight) infants were tested at 6, 7, and/or 8 months of age (corrected age for preterms) on a battery of problems assessing visual recognition memory and tactual-visual cross-modal transfer. At all 3 ages, scores obtained on aggregates of 6-11 problems in the battery significantly predicted 3-year Stanford-Binet IQ: correlations ranged from r = .37 to r = .63, and clustered between r = .50 and r = .60. When aggregates from 2 or 3 ages were used as predictors, multiple correlations were as high as R = .60 and R = .70. Cutoffs for predicting children at risk for mental retardation (IQ less than 70) or cognitive delay (IQ less than 85) showed reasonable sensitivity and specificity, although low scores were poor at detecting IQs less than 70. The internal consistency of composites, indexed by alpha coefficients, was unexpectedly low, primarily because the problems shared little variance. However, stability coefficients between assessments as much as 1 and 2 months apart were moderate in magnitude, ranging from r = .30 to r = .50. Considering the high degree of predictive validity, the stability figures appear to be better estimates of reliability for these measures than are indices of internal consistency. The relations reported here were similar for both full-terms and preterms.

Age Factors↗
PubMed1988

Information processing in seven-month-old infants as a function of risk status.

7-month-old full-terms and high-risk preterms (less than 1,500 grams at birth) were compared on problems of visual recognition memory and tactual-to-visual cross-modal transfer. On the visual problems, preterm infants showed significantly less differential attentiveness to novelty than full-terms. They also required longer exposure times during visual familiarization, primarily because of longer pauses between fixations. Preterms and full-terms exhibited different patterns of looking, as indicated by the duration of fixation and the frequency in shifts of gaze. On the cross-modal problems, preterms and full-terms both exhibited similar and significant preferences for familiar rather than novel stimuli, a direction of preference which suggests that these problems were relatively difficult for both groups. For the preterms, novelty and exposure-time scores were found to be related to several medical risk factors. Novelty preferences were compromised in preterms who had suffered RDS postnatally, particularly those who had required prolonged mechanical ventilation. In general, high-risk preterms exhibited deficits in visual recognition memory and in the ability to recruit, sustain, and shift attention.

Attention↗
PubMed1986

A recessive circadian clock mutation at the frq locus of Neurospora crassa.

A circadian clock mutant of Neurospora crassa, the most distinctive characteristic of which is the complete loss of temperature compensation of its period length, maps to the frq locus where seven other clock mutants have previously been mapped. This mutant, designated frq-9, is recessive to the wild-type allele and to each of the other frq mutants; thus, it differs from the other mutants, which show incomplete dominance to wild type and to each other. Complementation analysis suggests either that the frq locus is a single gene or that frq-9 is a deletion that overlaps adjacent genes. Preliminary efforts at fine structure mapping have indicated that recombination between certain pairs of frq mutations is less than 0.005%, a distance consistent with the locus being a single gene. The recessive nature of frq-9, coupled with complete loss of temperature compensation, suggests that this mutant may represent the null phenotype of the locus and that the frq gene is involved in the temperature compensation mechanism of the clock.--Genetic mapping studies have placed the frq locus on linkage group VIIR, midway between oli (oligomycin resistance) and for (formate auxotrophy), about 2 map units from each, and clearly indicate that frq and oli are separate genes.

Alleles↗
PubMed1986

Loss of temperature compensation of circadian period length in the frq-9 mutant of Neurospora crassa.

A new circadian clock mutant of Neurospora crassa has been isolated, whose most distinctive characteristic is the complete loss of temperature compensation of its period length. The Q10 of the period length was found to be equal to about 2 in the temperature range from 18 degrees to 30 degrees C. The period length was also found to be dependent on the composition of the medium, including the nature and concentration of both the carbon source and the nitrogen source. Although the rate of the clock and the growth rate were directly related when affected by varying the temperature, they were inversely related when altered by changing the composition of the medium. Therefore, the mutation has not simply coupled clock rate to growth rate in this strain. The mutation maps to the frq locus, where seven other clock mutations previously studied also map. Therefore, this mutant has been called frq-9. Since several of the other frq mutants show partial loss in temperature compensation, it is suggested that the frq gene or its product is closely related to the temperature compensation mechanism of the circadian clock of Neurospora.

Circadian Rhythm↗
PubMed1985

Sexual orientation after prenatal exposure to exogenous estrogen.

Thirty women aged 17 to 30 years with documented prenatal exposure to the nonsteroidal synthetic estrogen diethylstilbestrol (DES) were compared to thirty women of similar demographic characteristics from the same medical clinic who had a history of abnormal Pap smear findings. A subsample of the DES women were also compared to their DES-unexposed sisters. Sexual orientation in its multiple components was assessed by systematic semistructured interviews. In comparison to both control groups, the DES women showed increased bisexuality and homosexuality. However, about 75% of the DES women were exclusively or nearly exclusively heterosexual. Nonhormonal and hormonal interpretations of these findings are discussed.

Adolescent↗
PubMed1984

Sex-dimorphic behavior in childhood subsequent to prenatal exposure to exogenous progestogens and estrogens.

Thirteen boys and 15 girls with a history of prenatal exposure to medroxyprogesterone acetate only and 22 boys and 15 girls with exposure to a variety of progestogens and estrogens singly or in combination were studied at age 8-14 years in comparison to closely pair-matched, unexposed controls. This report concerns the findings on sex-dimorphic behavior as assessed by separate interviews with the child and his/her mother. Hormone-exposed boys and controls differed little, while in girls prenatal sex hormone treatment seemed to be associated with some degree of increased stereotypic femininity.

Adolescent↗
PubMed1984

Effects of prenatal hormone exposure versus pregnancy complications on sex-dimorphic behavior.

The existing literature on human subjects indicates demasculinization as an effect of prenatal exposure to various exogenous sex hormones, except for 19-nor progestogens. For the samples described in Ehrhardt et al. (1984), the current study examines whether the demasculinization can be explained by pregnancy complications. Corresponding covariates were constructed. In order to permit parametric analysis, the primary rating scales used previously were factor-analyzed and aggregated to form cluster scales where feasible. The factor analysis also demonstrated the existence of a general factor of sex-dimorphic behavior. Subsequent case-control comparisons by t test and by analysis of covariance for the general-factor and cluster scales showed that pregnancy complications do not explain the modest demasculinization effects of prenatal hormone exposure observed in females. A few paradoxical results emerged in males, likely to be due to chance.

Estrogens↗
PubMed1984

Psychosexual milestones in women prenatally exposed to diethylstilbestrol.

Thirty women aged 17 to 30 years with a record-confirmed history of prenatal exposure to diethylstilbestrol (DES) were compared to 30 women of similar age and demographic background with a history of abnormal Pap smear findings. Heterosocial and heterosexual histories were assessed by systematic semistructured interviews. The groups differed neither in the age at menarche nor in the age at attainment of various psychosexual milestones.

Adolescent↗