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PubMed2000

Differential expression of two CYP1A genes in rainbow trout (Oncorhynchys mykiss).

Differential expression of two rainbow trout CYP1A genes was measured in vivo and in vitro in response to treatment with the model CYP1A inducers beta-naphthoflavone (BNF), 3-methylcholanthrene (3-MC), isosafrole (ISF), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, only in vitro). Originally described by Berndtson and Chen (Arch. Biochem. Biophys. 310, 187-195, 1994) as CYP1A1 and CYP1A2, these genes were renamed CYP1A3 and CYP1A1, respectively, by the P450 nomenclature committee. A significant, differential, inducer-dependent induction of the two CYP1A mRNAs, as measured by RNase protection assay, was observed in vivo. CYP1A3 and CYP1A1 mRNA levels in liver were significantly induced 50- and 18-fold, respectively, following ip injection with BNF. Conversely, CYP1A3 and CYP1A1 mRNA levels were significantly induced 5- and 66-fold, respectively, following ip injection with 3-MC. Isosafrole had no significant effect on in vivo induction of CYP1A mRNA levels. In primary cultures of hepatocytes, BNF, 3-MC, ISF, as well as TCDD all significantly induced CYP1A3 and CYP1A1 mRNA levels compared to controls. The differential induction of the two CYP1A genes was not as evident in vitro as in vivo. In addition, reanalysis and sequence comparison of the these two trout CYP1A genes with the first trout CYP1A cDNA described by Heilmann et al. (DNA 7, 379-387, 1988) indicate that the Heilmann cDNA is a hybrid of the two trout genes. The 5' portion of the cDNA sequence (212 bp) was determined by sequencing of a genomic clone and is 100% identical to the trout CYP1A3 gene. The majority of the cDNA sequence (2377 bp), however, was sequenced from a partial cDNA clone and is 99.2% identical to trout CYP1A1. Although the nomenclature of these two trout CYP1A genes is undergoing revision, these results demonstrate a differential, inducer-dependent response to model mammalian CYP1A inducers.

Animals↗
PubMed1996

Adjusted variable plots for Cox's proportional hazards regression model.

Adjusted variable plots are useful in linear regression for outlier detection and for qualitative evaluation of the fit of a model. In this paper, we extend adjusted variable plots to Cox's proportional hazards model for possibly censored survival data. We propose three different plots: a risk level adjusted variable (RLAV) plot in which each observation in each risk set appears, a subject level adjusted variable (SLAV) plot in which each subject is represented by one point, and an event level adjusted variable (ELAV) plot in which the entire risk set at each failure event is represented by a single point. The latter two plots are derived from the RLAV by combining multiple points. In each point, the regression coefficient and standard error from a Cox proportional hazards regression is obtained by a simple linear regression through the origin fit to the coordinates of the pictured points. The plots are illustrated with a reanalysis of a dataset of 65 patients with multiple myeloma.

Biometry↗
PubMed1990

A ZFY-negative 46,XX true hermaphrodite is positive for the Y pseudoautosomal boundary.

Two loci on the short arm of the human Y chromosome have recently been described as candidates for the testis determining factor (TDF); namely, ZFY, and a locus distal to ZFY, near the pseudoautosomal boundary. We have previously reported on seven 46,XX true hermaphrodites and one 45,X mixed gonadal dysgenesis case all presenting with testicular tissue in their gonads in the apparent absence of Y-specific DNA sequences. A reanalysis of these cases shows them all to lack ZFY, but one 46,XX true hermaphrodite carries sequences next to the Y pseudoautosomal boundary. This case provides further evidence for assigning the TDF locus very close to the pseudoautosomal region on Yp.

Base Sequence↗
PubMed1988

Enhanced sprouting of retinotectal fibers after early superior colliculus lesions in hamsters treated with gangliosides.

The effects of exogenous gangliosides on sprouting of optic tract axons was studied in hamsters which, after a right tectal lesion on the day after birth (P1), had an abnormal retinotectal projection from the left eye to the left superior colliculus (SC). Sprouting of these axons was induced by removing the competing input by right eye removal on postnatal day 9 (P9). Intraperitoneal GM1, given daily and started on P9, significantly stimulated the sprouting response. This was demonstrated by Fink-Heimer silver staining of anterograde axonal degeneration three days after the left eye was removed on P36. Terminal fields in the left SC were, in average, twice as large compared to controls. An estimate of the total number of terminals (silver stained particles) revealed a value of 7.9 X 10(6) for GM1 and 3.2 X 10(6) for control hamsters, respectively. Diencephalic structures which also receive collateral input from the sprouting optic tract did not show any alterations in the size of the terminal field due to GM1-treatment, suggesting that, in vivo, gangliosides fail to initiate sprouting in areas that have not previously been denervated. Unexpectedly, GM1-treated hamsters also had significantly smaller right SC damage and less left damage near the midline. Subsequent reanalysis of the data based on a lesion-matching procedure indicates that effects on reducing atrophy were independent of the GM1-enhanced sprouting of retinofugal axons. These findings provide the first direct evidence that exogenous GM1 stimulates lesion-induced axon sprouting in the mammalian brain.

Animals↗
PubMed1979

Detection of rare major genes in lipid levels.

A statistical test of polygenic inheritance (TPI) against the alternative of a rare major gene is presented. It is designed for a random sample of quantitative observations on index cases and siblings of those index cases (probands) selected on the basis of the observed measurements of these probands. The test focuses on an increase of the variance of siblings of probands over its value under polygenic inheritance, such an increase being expected in the presence of a major gene producing a shift of the quantitative observations. Certain data on lipids are then analyzed by this test. A major gene can tentatively be confirmed for triglycerides but not for cholesterol. In addition, the values of all index cases are subjected to an analysis of a mixture of normal distributions (NOCOMP computer program), resulting in a significant second component for triglycerides but not for cholesterol. For both TPI and NOCOMP, the exponent in a power transformation is estimated by maximum likelihood simultaneously with all other parameters, so that these analysis methods are robust against a wide range of skewness in the data, which is demonstrated by manipulation of the observations and their reanalysis.

Analysis of Variance↗
PubMed1986

Mutational specificity of a proof-reading defective Escherichia coli dnaQ49 mutator.

The dnaQ (mutD) gene product which encodes the epsilon-subunit of the DNA polymerase III holoenzyme has a central role in controlling the fidelity of DNA replication because both mutD5 and dnaQ49 mutations severely decrease the 3'-5' exonucleolytic editing capacity. It is shown in this paper that more than 95% of all dnaQ49-induced base pair substitutions are transversions of the types G:C-T:A and A:T-T:A. Not only is this unusual mutational specificity precisely that observed recently for a number of potent carcinogens such as benzo(a) pyrene diolepoxide (BPDE) and aflatoxin B1 (AFB1), which are dependent on the SOS system to mutagenize bacteria, but it is also seen for the constitutively expressed SOS mutator activity in E. coli tif-1 strains as well as for the SOS mutator activity mediated gap filling of apurinic sites. Because the G:C-T:A and A:T-T:A transversions can either result from the insertion of an adenine across from apurinic sites or arise due to the incorporation of syn-adenine opposite a purine base, we postulate that the DNA polymerase III holoenzyme also has a reduced discrimination ability in a dnaQ49 background. The introduction of a lexA (Ind-) allele, which prevents the expression of SOS functions, led to a significant reduction in the dnaQ49-caused mutator effect. Both, the mutational specificity observed and the partial lexA+ dependence of the mutator effect provoke a reanalysis of the hypothesis that the DNA polymerase III holoenzyme can be converted into the postulated but until now unidentified SOS polymerase.

Anticodon↗
PubMed1988

Is HLA matching relevant in pancreas transplantation? A registry analysis.

The International Pancreas Transplant Registry data base was analyzed for the effect of HLA and mismatching on pancreas survival rate. Typing data was available for both donor and recipient at the A, B and DR loci in 524 of 855 cadaver cases reported since 1982 and in 37 related cases. For cadaver cases, the 1-year functional survival rates for grafts mismatched at less than or equal to 3 (N = 163) versus greater than or equal to 4 (N = 361) A, B and DR antigens were 49% versus 39% (P = 0.121); for technically successful (TS) cases the rates were 66% (N = 123) versus 54% (N = 257) (P = 0.038). An effect was seen at A, B and DR loci, but the differences were not significant when considered separately. THe analysis of TS related donor transplants showed a 1-year graft survival rate of 89% for HLA mismatched donors (N = 11) and of 80% for HLA identical donors (N = 11). The survival rate of the latter is significantly higher (P = 0.046) than that of the TS cadaver donor transplants (59% at 1 year, N = 361). The data suggest that the results of pancreas transplantation will be improved by minimizing HLA mismatches. However, a reanalysis with a more complete data base is needed before firm conclusions can be drawn.

Graft Survival↗
PubMed1985

[Validity of the Eppendorf Mood-Drive Scale].

The paper examines the validity of the Eppendorfer Mood and Drive Scale (ESTA III). ESTA III is a self-rating instrument for evaluating the effect of therapy and for studying the course of affective psychoses. Empirical research on the validity of the scale has been carried out solely by the author of the test. Subsequent to a critical review of hitherto existing research on the validity of the instrument, our own validity studies are discussed. Our studies cast doubt on the concurrent validity of the instrument (comparison with the adjective check list/EWL-K). Analysis of our own data and Reanalysis of the data published by the author of ESTA III do not support the construct validity of the instrument.

Bipolar Disorder↗
PubMed1981

Inter-animal olfactory cues in operant drug discrimination procedures in rats.

Olfactory cues from prior subjects in operant chambers were shown to be an effective stimulus which rodents could use to direct lever selection in a typical operant drug discrimination (DD) paradigm. Such cues persisted for very long periods of time (16 h), and were deposited after very short (5 min) operant sessions. In extinction tests inter-animal olfactory cues exerted very strong stimulus control over lever selection. Furthermore, such cues were not specific to individual rodent subjects but were generalizable between subjects. Inter-animal cues directing level selection could be abolished by cleaning operant manipulanda with a 10% alcohol solution. Reanalysis of some DD data previously reported by one of the authors (Goudie 1977) indicated that this specific earlier study (and by implication perhaps other studies) might have been confounded by inter-animal cues. In a DD study with nicotine it was found that the drug cue was antagonized by mecamylamine for all subjects except those who had a reliable olfactory cue from prior subjects to direct lever selection (subjects who possessed both an olfactory and a drug cue to direct lever selection responded in a way suggesting that the exteroceptive olfactory cue controlled behaviour rather than the interoceptive drug cue). These findings indicate that inter-animal olfactory cues could be of considerable methodological significance in DD studies. The possible significance of such cues has not previously been reported upon in detail, and in reports of many DD studies there do not appear to be explicit indications that inter-animal cues have been adequately controlled.

Animals↗
PubMed1981

Limbitrol (amitriptyline plus chlordiazepoxide) revisited.

A reanalysis of 4-week data from a recently published study (Feighner et al. 1979) clearly demonstrate that in a significant subgroup of highly depressed patients who also suffer from at least moderate anxiety, significant treatment differences in favor of Limbitrol over AT were present not only after 1 or 2 weeks, but also after 4 weeks of treatment. These differences were not present in the less sick patients, a population in which AT was slightly favored. These findings suggest that not only is Limbitrol more effective than AT alone for a heterogeneous group of depressed patients with some concomitant anxiety during the early phases of treatment, but remains more effective that AT for a significant subgroup of highly depressed patients after 4 weeks of treatment.

Adult↗
PubMed1978

Concentration quenching in chlorophyll-alpha and relation to functional charge transfer in vivo.

Chlorophyll-alpha in ordinary solvents exhibits concentration quenching. Dimeric chlorophyll is reasonably well confirmed as the quenching species, by a critical reanalysis of available data on concentration dependence and on spectral features, in ordinary solvents, and in several analogous quenching environments. This quenching in the dimer in vitro is somewhat less firmly analyzed as due to a new fast internal conversion. Much peripheral evidence supports transient charge transfer as the cause of internal conversion. The same evidence points to a strong similarity to functional charge transfer in vivo. I suggest that inability to extract P680 may be due to its conversion to a form resembling P700 by addition of water. A number of straightforward experiments are suggested to test these proposals. In particular, it is desirable to test for the existence of a vibronic perturbation (from a higher npi* state) in the dimer, as an alternative to charge transfer for explaining the "observed" internal conversion. Such a vibronic cause would raise interesting problems for phototrap function in vivo.

Chlorophyll↗
PubMed1979

The structured interview and questionnaire methods of assessing coronary-prone behavior in male and female college students.

Several self-report measures of type A behavior were compared with the Rosenman and Friedman structured interview method of assessment in male and female college students. The student version of the Jenkins Activity Survey was found to correlate relatively weakly with the interview for both males and females, while scales derived from the Gough and Thurstone inventories showed moderate correlations with interview typing for both sexes. A brief scale derived from a recent reanalysis of the Framingham study correlated with the interview appreciably greater for females than for males. In all, these data suggest the need for caution in using only paper-and-pencil tests to assess type A behavior.

Adolescent↗
PubMed1988

Attaining and maintaining preparation: a comparison of attention in hyperactive, normal, and disturbed control children.

The hypothesis that hyperactive children have a deficit in sustained attention was investigated. Eighteen children who had attention deficit disorder with hyperactivity (ADDH), aged 7 to 11 years, were compared with children who had conduct disorder (n = 15), mixed conduct disorder and ADDH (n = 26), emotional disorder (n = 18), or learning disability (n = 22), and with normal controls (n = 15). The subjects were tested on three versions of the Continuous Performance Task. Sustained attention was assessed from performance with increasing time on task and from ability to prepare attention in response to a warning. Performance of all subjects deteriorated with increasing time and improved with the opportunity to prepare attention. Hyperactive subjects were not more adversely affected by increasing time, nor did they benefit less than controls from the opportunity to prepare attention. Data reanalysis after rediagnosis according to ICD-9 criteria did not change the results. This study did not confirm the hypothesis that hyperactive children have a unique sustained attention deficit.

Affective Symptoms↗
PubMed1980

Visual discrimination deficits of reading-disabled children: sex artifact?

Several theorists have suggested that deficits in visual discrimination play an etiological role in the development of reading deficits in children who are diagnosed as learning-disabled. Supporting this theory, a number of studies have shown that disabled readers make more errors on visual discrimination tasks than do good readers. The present study, however, suggests that those findings may have been due to a sex-difference artifact. Thirty-six 8- and 9-year-old good readers and reading-disabled children of both sexes responded to 40 matching items under untimed conditions. Males made more errors than females, but overall, reading-disabled children made no more errors than good readers. These findings, along with a reanalysis of previous studies, suggest that because reading disabilities are more common in males, evidence construed as supporting a visual discrimination hypothesis may have been an artifact of a sex difference in studies in which sex was not controlled.

Child↗
PubMed1991

A population analysis of the pharmacokinetics and pharmacodynamics of midazolam in the rat.

The concentration-EEG effect relationship of midazolam in the rat was studied from a population perspective. Plasma concentration and EEG effect data from 27 rats were available for analysis. Effect parameters derived from aperiodic EEG analysis were used as effect parameters. The population analysis gave results that were similar to the sample theory estimates (means s and SDs) obtained from the fits to individual data sets. Reanalysis of the EEG data using mean population pharmacokinetic parameters as input to the pharmacodynamic model led to poorer estimation of the pharmacodynamic parameters: particularly EC50. Inclusion of one observed plasma concentration per individual significantly improved the estimation of the pharmacodynamic parameters and led to results that were virtually indistinguishable from those obtained using complete pharmacokinetic data.

Animals↗
PubMed1992

A biometrical genetic approach to chromosome analysis in Drosophila: detection of epistatic interactions in geotaxis.

Chromosome analysis has been widely used as a first step in elucidating the genetic architecture of several behaviors of Drosophila melanogaster. These chromosome studies have generally used incomplete designs or fairly simple statistical analyses. Here I reanalyze two data sets on geotaxis from Pyle (1978) and Ksander (1966) using a biometrical genetic design. Results from the biometrical genetic reanalysis suggest that individual differences in geotaxis might be due to genes on all three major chromosomes which show extensive epistatic interactions.

Animals↗
PubMed1993

Sensation seeking in opposite-sex twins: an effect of prenatal hormones?

Intrauterine hormones and position with respect to male and female littermates influence sexually dimorphic adult behavior in litter-bearing animals. Opposite-sex dizygotic twins offer the opportunity to examine analogous effects on sex-related human behaviors. To illustrate this approach, Sensation Seeking Scale (SSS) scores from 422 British twin pairs, including 51 opposite-sex pairs (Zuckerman, M., et al., J. Consult. Clin. Psychol. 46:139-149, 1978), were reanalyzed. Zuckerman et al. (1978) have shown that some aspects of sensation seeking are consistently increased in males relative to females. In comparing age-adjusted data for opposite and same-sex twins, our reanalysis demonstrated the predicted increase in sensation seeking in female members of opposite-sex pairs. Results were significant for measures of disinhibition, experience seeking, and overall sensation seeking. In contrast, male opposite-sex twins were not significantly different from male same-sex twins. Although psychosocial explanations of the increased sensation seeking in opposite-sex female twins cannot be excluded, these finding are consistent with hypothesized in utero hormonal influences on later behavioral development.

Adolescent↗
PubMed1979

Resolution of block neutralization test curves into components of the foot-and-mouth disease virus system.

Classic neutralization studies by Fazekas de St. Groth and Webster (8) on mixtures of influenza viruses and mixtures of rabbit antisera are reinterpreted in terms of a percentage contaminant in the stock used for the dilution series. A very small amount of a different virus changes the shape of quantal assay curves considerably, but even a large amount of a different antiserum has negligible effect on the shape and merely shifts the curve along the serum dilution axis. These conclusions are the reverse of the authors, who only considered an absolute amount of another component in all dilution tubes. An artificial mixture of 2.7 percent O8 in O1 foot-and-mouth disease virus strains was tested against anti-O1 serum assaying in suckling mice. The small amount of O8 virus greatly altered the shape of the neutralization curve in the direction expected from the reanalysis of the influenza literature data. Results from artificial mixtures are used to explain what were hitherto anomalously broad neutralization curves for some other foot-and-mouth disease strains given by Booth et al. (1) Many of the virus stocks studied can now be postulated as a natural mixture of related virus strains. In fact, the O1 and O8 stocks used might also be of themselves mixtures. These virus strains also exhibit still a further test complication in that the virus-antibody reaction appeared to shift away from complexes on dilution immediately prior to assay.

Antigen-Antibody Reactions↗