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Biomedical subjects

A Pawlak

Publications and source records attributed to A Pawlak.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Clinical heterogeneity of myelomeningocele as evidence of multisite closure of the neural tube].

Eighty-two patients treated surgically for myelomeningocele or myelodysplasia between 1945 and 1993 are presented. Family and environmental history has been studied. The presence of genetic markers (HLA B27, ABO, Rh) has been investigated. Heterogenicity of localization and type of defect in the series reviewed has been found. Associations between certain genetic features confirm multisite mechanism of closure of the neural tube. The relationship between site of neural tube defect and concurrence of developmental defects has been substantiated. A higher site often results in multiple defects.

ABO Blood-Group System↗
PubMed1993

Double-blind placebo crossover study of cyproterone acetate in the treatment of the paraphilias.

Cyproterone acetate is a powerful antiandrogen used in the treatment of the paraphilias for at least a decade. Studies have reported it effective in reducing the recidivism rates of sexual crimes perpetrated by men. It acts through competitive inhibition of the androgen receptors blocking the effects of testosterone and dihydrotestosterone. Systematic clinical study of its effectiveness and its clinical effects on sexual behavior is lacking, however. In the current study 19 paraphilic men who had also recidivated in a variety of sexual crimes were treated with cyproterone acetate and placebo in a double-blind crossover design. The use of active drug was associated with a significant reduction of some aspects of sexual behavior, particularly sexual fantasies. There were also significant effects on levels of circulating sex hormones and some effects on physiological measurements and self-reports of sexual arousal.

Adult↗
PubMed1993

Effects of cyproterone acetate on sexual arousal patterns of pedophiles.

The antiandrogen treatment of sexual offenders has been shown to reduce the recidivism rate. The mechanism of action has been assumed to be through asexualization with its secondary effects on sexual behavior. This study shows that the mechanism may be more complex and may involve a differential effect on sexual arousal patterns. Treatment responses may differ in high and low plasma testosterone groups.

Adult↗
PubMed1992

The paraphilias: a multiplicity of deviant behaviours.

The DSM-II and DSM-III both allow for multiple diagnoses. The DSM-III acknowledges that a patient may have multiple paraphilias but the true nature and extent of the multiplicity has only been documented recently. In order to study the degree of crossover between the various paraphiliac acts, a study of men who admitted to at least one paraphilia was conducted. A proportional index of multiple deviation was obtained. In addition, the mean number of admitted sexually deviant incidents per paraphilic category was computed as an estimate of the extent of deviant acts committed by this population. The results indicated that paraphiliacs tend to have multiple types of sexual aberrations as well as a high frequency of deviant acts per individual.

Adult↗
PubMed1991

Estradiol down regulates the binding activity of an avian vitellogenin gene repressor (MDBP-2) and triggers a gradual demethylation of the mCpG pair of its DNA binding site.

A negative regulating protein (MDBP-2) from rooster liver nuclear extracts binds preferentially to a methylated promoter region 5'TTCACCTTmCGCTATGAGGGGGATCATACTGG3' of the avian vitellogenin II gene (Nucleic Acids Res. 19, 1029-1034, 1991). Treatment of adult and immature roosters with estradiol results in a 90% decrease in the binding activity of MDBP-2 within three days. This corresponds to the level found in egg laying hens. The decrease in the binding activity of MDBP-2 precedes the onset of vitellogenin gene transcription. At the same time, there is a two-fold increase in the binding activity of NHP-1 (tested with the same oligonucleotide as for MDBP-2), a protein thought to be involved in the active demethylation of DNA. The methylated oligonucleotide binds either MDBP-2 or NHP-1 and there is no complex formation between the two proteins and DNA. Estradiol treatment does not change the equilibrium binding constant of MDBP-2 which is about 10(-9)M for the methylated oligonucleotide. The early kinetics of demethylation of the mCpG pair in the binding site of MDBP-2 was studied by means of genomic sequencing. A low level of demethylation of mCpG starts gradually on both DNA strands already 4 hours after estradiol treatment during the lag phase of vitellogenin mRNA synthesis. It is concluded that the lowering of the binding activity of MDBP-2 may have a stronger effect on the derepression of the gene than the slow demethylation of MDBP-2 DNA binding site. The role of the methylated CpG is to assure a high binding affinity of the repressor to DNA.

Animals↗
PubMed1991

An avian 40 KDa nucleoprotein binds preferentially to a promoter sequence containing one single pair of methylated CpG.

In vitro transcription competition with oligonucleotides has shown that a down regulating factor can be displaced by a methylated oligonucleotide covering a specific region of the avian vitellogenin II gene promoter (Proc. Natl. Acad. Sci USA, (1990) 87, 3047-3051). Gel mobility shift and competition assays show that a protein binding preferentially to methylated DNA (MDBP-2) is present in fractionated hen and rooster nuclear extracts. The protein(s) bind to the methylated sequence 5' TTCACCTTmCGCTATG-AGGGGGATCATACTGG' 3' (nucleotide positions +2 to +32) of the vitellogenin II promoter and not to other methylated DNA sequences. Contact points of the MDBP-2 with DNA were studied by DNA binding interference experiments with partially depurinated and depyrimidinated oligonucleotides. The protein has an approximate molecular weight of 40 KDa and is mainly found in the liver and oviduct. Proteolytic clipping bandshift assays of the MDBP-2 from rooster and hen liver nuclear extracts indicate that the protein from the two sources are different. In vitro transcription experiments show that the addition of a purified nuclear fraction containing the addition of a purified nuclear dependent manner the transcription of vitellogenin II gene.

Animals↗
PubMed1990

An alternatively processed mRNA specific for gamma-glutamyl transpeptidase in human tissues.

Human gamma-glutamyl transpeptidase (GGT)1 is composed of two subunits derived from a single precursor (Nash, B., and Tate, S.S. (1984) J. Biol. Chem. 259, 678-685; Finidori, J., Laperche, Y., Tsapis, R., Barouki, R., Guellaën, G., and Hanoune, J. (1984) J. Biol. Chem. 259, 4687-4690) consisting of 569 amino acids (Laperche, Y., Bulle, F., Aissani, T., Chobert, M.N., Aggerbeck, M., Hanoune, J., and Guellaën, G. (1986) Proc Natl. Acad. Sci. U.S.A. 83, 937-941). In the present study we report the cloning of an altered form of this precursor from human liver. We have isolated two clones, one 2,632 base pairs (bp) long from a fetal liver cDNA library and one 926 bp long from an adult liver cDNA library, each containing a 22-bp insertion that introduces a premature stop codon and shortens the open reading frame to 1,098 bp when compared with known human cDNA sequences specific for GGT. Sequence analysis of a human genomic GGT clone shows that this insertion of 22 bp is generated by a splicing event involving an alternative 3'-acceptor site. By polymerase chain reaction experiments we demonstrate that the alternatively spliced mRNA is present in polysomes from the microsomal fraction of a human hepatoma cell line (Hep G2) and thus could encode an altered GGT molecule of 39,300 Da (366 amino acids) encompassing most of the heavy subunit which is normally 41,500 Da (380 amino acids). The altered mRNA is detected in various human tissues including liver, kidney, brain, intestine, stomach, placenta, and mammary gland. This report is the first demonstration of an alternative primary sequence in the mRNA coding for GGT, a finding that could be related to the presence of some inactive forms of GGT detected in human tissues.

Adult↗
PubMed1990

Positive and negative regulatory elements of chicken vitellogenin II gene characterized by in vitro transcription competition assays in a homologous system.

A homologous in vitro transcription system was developed in which the cloned chicken vitellogenin II gene is faithfully transcribed by extracts prepared from chicken liver nuclei. The use of template deleted of its upstream region resulted in poor transcriptional efficiency, as did the use of extracts prepared from rooster liver, in which the gene is silent. The influence of individual cis elements was determined by transcription competition analysis. Oligonucleotides covering greater than 500 base pairs of the promoter region were used as competitor DNA in the in vitro reactions. Competition with an oligonucleotide covering part of the expression-specific DNase I hypersensitivity site B2, which contains a demethylation site, mCpG, at nucleotide position + 10, increased transcription of the gene, suggesting the binding of a repressor to this region. The enhancement of transcription was even more pronounced when the same oligonucleotide was methylated at the corresponding + 10 cytosine. Competition with oligonucleotides covering the TATA box, or the estrogen response element half-palindromic motif (GGTCA) at nucleotide positions -198 to -194, resulted in a large decrease in vitellogenin gene transcription, indicating that strongly activating factors bind to these regions. Competing oligonucleotides covering other GGTCA-containing motifs situated further upstream at nucleotide positions -292 to -288, -367 to -351, and -626 to -614 were increasingly less effective in inhibiting transcription. The results indicate that factors other than the estrogen receptor are involved in transcriptional activation of the vitellogenin II gene.

Animals↗
PubMed1989

Different gamma-glutamyl transpeptidase mRNAs are expressed in human liver and kidney.

In human, the two subunits of gamma-glutamyl transpeptidase (GGT) arise from a common precursor encoded by a multigene family. Until now, a single specific coding sequence for this precursor (type I) has been identified in human placenta and liver. In the present study, we have isolated from a human kidney cDNA library, a GGT specific clone (0.8 Kb). The sequence of which (type II) i) covers the carboxy terminal part of the GGT precursor, ii) exhibits 22 point mutations and a 30 bp deletion as compared to the type I GGT sequence. The sequencing of a human genomic clone reveals that this type II GGT mRNA is encoded by a different gene than the type I GGT mRNA. Both type I and type II GGT mRNAs are expressed in human liver, while almost exclusively type II GGT mRNA is detected in human kidney.

Adult↗
PubMed1988

Nucleotide sequence and tissue distribution of the human mitochondrial aspartate aminotransferase mRNA.

The cDNA of human mitochondrial aspartate aminotransferase (E.C.2.6.1.1.) was isolated from a human liver cDNA library using a rat mitochondrial aspartate aminotransferase cDNA as probe. The sequence of this cDNA gives a predicted aminoacid sequence for the human presequence and for the human mature protein exhibiting respectively 93% and 95% homology with rat sequences. A Northern blot of total RNA, isolated from various human tissues and hybridized with this cDNA, revealed a single 2.4 Kb RNA band. Mitochondrial aspartate aminotransferase RNA was clearly detected in human kidney, placenta, stomach and spleen as well as in both fetal and adult liver.

Amino Acid Sequence↗
PubMed1988

gamma-Glutamyl transpeptidase: a single copy gene in the rat and a multigene family in the human genome.

gamma-Glutamyl transpeptidase (GGT) genomic sequences were isolated from rat and human libraries using a rat GGT cDNA as a cross-species hybridization probe. Characterization of the human GGT clones by restriction mapping clearly establishes that at least four different GGT genes or pseudogenes are present in the human genome. All the rat genomic clones cover a 12.5-kilobase sequence and exhibit a unique restriction pattern. A precise quantitation of the rat GGT gene copy number by Southern blot analysis demonstrates that this sequence is present as a single copy/rat haploid genome. Therefore, the GGT gene organization is different between rat and human species; this raises the possibility of different regulatory mechanisms in the two species.

Animals↗
PubMed1988

Specific modulation by ethanol of the protein synthesis pattern in the C2 rat hepatoma cell line.

The effect of ethanol on protein synthesis in the C2 rat hepatoma cell line was analyzed by two-dimensional gel electrophoresis after the labeling with [35S]methionine of cells that were untreated or had been treated with 180 mM ethanol. In this cell line, this concentration of ethanol is known to induce gamma-glutamyl transpeptidase, a marker of alcoholism in man (Barouki et al., Hepatology 1983; 3: 323-329). In the present work we demonstrate that ethanol, besides causing a slight decrease in overall protein synthesis (less than 25%), primarily regulates the expression of two unique proteins among 1500 labeled products that were analyzed: one of these was induced and did not correspond to gamma-glutamyl transpeptidase, and one was repressed after 20 h of ethanol treatment. We conclude that the set of hepatic proteins altered by ethanol is likely to be very limited in number, which reflects the specificity of alcohol action on protein synthesis in the C2 cell line.

Animals↗
PubMed1988

The assessment of deviant sexual arousal as a function of intelligence, instructional set and alcohol ingestion.

Sexual offenders who had been referred for a forensic evaluation were assessed in terms of their deviant sexual arousal by means of standard penile plethysmographic procedures. The sample was divided into Rapist and Nonrapist groups according to their sexual history and criminal charges. Penile circumference responses (PCR) and self-reported arousal to consenting sex, sexual assault, and physical assault were monitored. The assessments were repeated following subject instructions to suppress their arousal and following the ingestion of alcohol. The overall correlation between PCR and self-reported arousal was .65. An Alcohol-by-Offender Type interaction revealed that the lowering effect of alcohol on PCR occurred only among the Nonrapists. The suppression instruction increased Rapists' PCRs to Rape and Physical Assault presentations relative to consenting sexual narrations. When the data were examined in relation to intelligence, low IQ Rapists displayed greater responses to rape than high IQ Rapists. Under the influence of alcohol, low IQ Rapists displayed greater arousal regardless of the stimulus, while high IQ Rapists showed no change, and Nonrapists responded less than they did without alcohol. Comments concerning the accurate assessment of deviant sexual arousal and the identification of precursors to deviant sexual behaviour are made in view of the current findings.

Adult↗
PubMed1988

The clinical and forensic psychiatric issues of retifism.

The literature on the etiological theories, clinical manifestations and treatment of retifism (foot fetishism) and fetishisms in general are briefly reviewed. The case of a 27 year old married male foot-fetishist is presented with emphasis on the psychosexual development leading to the specific sexual deviation. The specific behavioural treatment consisted of covert aversive conditioning using self-reports of sexual urges and psychophysiological monitoring as objective measures of therapeutic change. The theoretical basis for the therapeutic response is discussed.

Adult↗
PubMed1987

Assignment of the human gamma-glutamyl transferase gene to the long arm of chromosome 22.

We have determined the chromosomal location of the human gene for gamma-glutamyltransferase (GGT). This study was done by in situ hybridization of human metaphase spreads with a rat cDNA probe specific for this enzyme and constructed from two clones previously characterized in our laboratory. The final construct had a 1.6-kb-long insert covering 92% of the coding sequence for GGT. The new insert was also freed of any GC tails introduced for the cDNA cloning, because we observed that these sequences were responsible for a high background. Using this probe for the analysis of 136 human metaphase spreads, we observed a strong specific signal on chromosome 22 at the interface of q111-112 and a minor peak in q131. Thus GGT might represent a new marker for the study of certain diseases which have chromosomal abnormalities at these loci.

Chromosome Banding↗
PubMed1987

Sadistic homosexual pedophilia: treatment with cyproterone acetate: a single case study.

This single case study demonstrates the effects of antiandrogen treatment on a subject with a very serious sexual deviation and a poor prognosis. It assesses the effects of cyproterone acetate (CPA) on an individual with a serious chronic organic brain syndrome combined with sadistic homosexual pedophilia. Furthermore, this individual had failed to respond to a behavioural treatment program and long-term milieu therapy. Finally, this case study is the first report of CPA differentially affecting penile responses to deviant and non-deviant stimuli.

Adult↗