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Biomedical subjects

G Schreiber

Publications and source records attributed to G Schreiber.

At least 37 records · Page 2Linked to original sources
PubMed2001

Exploring the relationship between timing of menarche and eating disorder symptoms in Black and White adolescent girls.

OBJECTIVE: This study examined the relationship between timing of sexual maturation and eating disorders symptoms in adolescent girls. METHOD: Data were collected over 10 years for a cohort of 1,213 Black girls and 1,166 White girls who were either 9 or 10 years old at study entry. Annually, girls' height and weight were measured and, biannually, girls completed self-report measures of eating disorders symptoms. RESULTS: Early-onset menarche is a risk factor for the development of body image and dieting concerns, but the effect of timing is due to the impact of early and late maturation on body weight. DISCUSSION: Findings underscore the importance of adiposity as a risk factor for poor mental health.

Adolescent↗
PubMed2001

Retinal anatomy and function of the transthyretin null mouse.

Vitamin A (retinol) is vital for the normal development and function of many tissues in the body including the eye. The purpose of this project was to characterize the retinal anatomy and function of the transthyretin (TTR) null mouse. Mice lacking TTR have been constructed by homologous recombination. Immunocytochemistry was performed to localize short and mid-long wavelength cone opsins as well as morphological examination of the entire retina in wild-type and TTR null mice. Visual function was assessed using the electroretinogram (ERG) and resulting waveforms were analysed in terms of receptoral and postreceptoral components. Retinal morphology of the TTR null mouse was normal. In addition, short and mid-long wavelength cone opsins were localized normally in both TTR null and wild-type retinae. Consistent with these findings, TTR null mice show no anomalies of receptoral (P3) nor post-receptoral (b-wave) ERG components compared with wild-type mice. The results suggest that although circulating plasma levels of retinol and retinol binding protein (RBP) are extremely low, this reduction has little effect on the retinal structure or function of the TTR null mouse. These data are consistent with the existence of mechanisms for the transport of retinol to the retina independent of the classical retinol-RBP-TTR complex.

Analysis of Variance↗
PubMed2001

Differential effects of the antipsychotics haloperidol and clozapine on G protein measures in mononuclear leukocytes of patients with schizophrenia.

AIMS: Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins were previously implicated in the pathophysiology and treatment of mood and other neuropsychiatric disorders. Recently we showed that untreated patients with schizophrenia have a significantly elevated dopamine-induced Gs protein function which is correlated with the severity of the psychotic symptoms. In contrast, an inverse picture with reduction in the function and the immunoreactivity of Gs protein was detected in patients with Parkinson's disease. The present study aims at investigating the effect of antipsychotic medications on dopamine-induced Gs protein hyperfunction in schizophrenia comparing the classical antipsychotic haloperidol and the newer antipsychotic clozapine, which is devoid of extrapyramidal side effects, on G protein measures. METHODS: G protein functional measurements coupled to beta-adrenergic, muscarinic, and dopamine receptors were undertaken through bacterial toxin sensitive, agonist enhanced [3H]-Gpp(NH)p binding capacity, substantiated by quantitative measures of Gs alpha, Gi alpha, and G beta subunit proteins through immunoblot analysis in mononuclear leukocytes obtained from patients with schizophrenia under haloperidol, or clozapine treatments in comparison with untreated patients with schizophrenia and healthy volunteers. RESULTS: Dopamine-induced Gs hyperfunction characteristic of untreated patients with schizophrenia was not detected under antipsychotic treatment with either haloperidol or clozapine. Haloperidol caused a significant decrease in Gs function and immunoreactivity below normal levels. The extend of reduction in Gs function was found to be correlated with the intensity of extrapyramidal side effects. The pattern of G protein subunits levels in patients with schizophrenia under haloperidol treatment resembles the one obtained in patients with Parkinson's disease. CONCLUSIONS: In the present study it is shown that G protein measurements in patients with schizophrenia under antipsychotic treatments can be used to biochemically monitor effects of antipsychotic medications in living patients. Moreover, these measurements may be used also for monitoring parkinsonian side effects induced by antipsychotic medications.

Adult↗
PubMed2001

Dynamic analysis of inter-words time intervals: a method to analyze the structure of communicative signals.

Speech analyses are usually focused on words as signifiers ignoring inter-words time intervals (IWIs), which are related to the 'form' of speech, rather than to its 'content'. Applying the method of power spectrum analysis to inter-vocalizations time intervals of bird singing, underlying periodic processes were detected. In contrast, human IWIs revealed non-periodicity, which may be random or chaotic. To differentiate between these two possibilities, the non-linear dynamic methods of unstable periodic orbits and correlation dimension were applied to show that IWIs are characterized by a low dimensional chaotic attractor. Its correlation dimension of 3.2 +/- 1.1 suggests a minimum number of four variables underlying the system. The methods developed in the present communication can be further applied: (a) for the measurement of specific alterations in the processes underlying the form of speech in human disorders, i.e., schizophrenia, (b) for the assessment of normal and pathological developmental aspects of speech processes in children; (c) for comparing communicative signals between humans and other species.

Adult↗
PubMed2001

Pseudoainhum of all fingers associated with Reynolds' syndrome and breast cancer: report of a case and review of the literature.

Pseudoainhum is a rare disorder characterized by digital constrictions leading to autoamputation. We report a bilateral pseudoainhum of all fingers in a 64-year-old fair-skinned woman with breast cancer, systemic scleroderma, and primary biliary cirrhosis. The overlap between scleroderma and primary biliary cirrhosis with antimitochondrial antibodies M2 is also known as Reynolds' syndrome. Although pseudoainhum has been associated with many conditions, this particular association is exceptional and has yet not been described.

Ainhum↗
PubMed2000

New structural and functional aspects of the type I interferon-receptor interaction revealed by comprehensive mutational analysis of the binding interface.

Type I interferons bind to two cell surface receptors, ifnar1 and ifnar2, as the first step in the activation of several signal transduction pathways that elicit an anti-viral state and an anti-proliferative response. Here, we quantitatively mapped the complete binding region of ifnar2 on interferon (IFN)alpha2 by 35 individual mutations to alanine and isosteric residues. Of the six "hot-spot" residues identified (Leu-30, Arg-33, Arg-144, Ala-145, Met-148, and Arg-149), four are located on the E-helix, which is located at the center of the binding site flanked by residues on the A-helix and the AB-loop. The contribution of residues of the D-helix, which have been previously implicated in binding, proved to be marginal for the interaction with the extracellular domain of ifnar2. Interestingly, the ifnar2 binding site overlaps the largest continuous hydrophobic patch on IFNalpha2. Thus, hydrophobic interactions seem to play a significant role stabilizing this interaction, with the charged residues contributing toward the rapid association of the complex. Relating the anti-viral and anti-proliferative activity of the various interferon mutants with their affinity toward ifnar2 results in linear function over the whole range of affinities investigated, suggesting that ifnar2 binding is the rate-determining step in cellular activation. Dose-time analysis of the anti-viral response revealed that shortening the incubation time of low-level activation cannot be compensated by higher IFN doses. Considering the strict dependence of the cellular response on affinity, these results suggest that for maintaining transcription of IFN-responsive genes over a longer time period, low but continuous signaling through the IFN receptor is essential.

Amino Acid Sequence↗
PubMed2000

Evaluation of direct and cooperative contributions towards the strength of buried hydrogen bonds and salt bridges.

An experimental approach to evaluate the net binding free energy of buried hydrogen bonds and salt bridges is presented. The approach, which involves a modified multiple-mutant cycle protocol, was applied to selected interactions between TEM-1-beta-lactamase and its protein inhibitor, BLIP. The selected interactions (two salt bridges and two hydrogen bonds) all involving BLIP-D49, define a distinct binding unit. The penta mutant, where all side-chains constructing the binding unit were mutated to Ala, was used as a reference state to which combinations of side-chains were introduced. At first, pairs of interacting residues were added allowing the determination of interaction energies in the absence of neighbors, using double mutant cycles. Addition of neighboring residues allowed the evaluation of their cooperative effects on the interaction. The two isolated salt bridges were either neutral or repulsive whereas the two hydrogen bonds contribute 0.3 kcal mol(-1 )each. Conversely, a double mutant cycle analysis of these interactions in their native environment showed that they all stabilize the complex by 1-1.5 kcal mol(-1). Examination of the effects of neighboring residues on each of the interactions revealed that the formation of a salt bridge triad, which involves two connected salt bridges, had a strong cooperative effect on stabilizing the complex independent of the presence or absence of additional neighbors. These results demonstrate the importance of forming net-works of buried salt bridges. We present theoretical electrostatic calculations which predict the observed mode of cooperativity, and suggest that the cooperative networking effect results from the favorable contribution of the protein to the interaction. Furthermore, a good correlation between calculated and experimentally determined interaction energies for the two salt bridges, and to a lesser extent for the two hydrogen bonds, is shown. The data analysis was performed on values of DeltaDeltaG(double dagger)K(d) which reflect the strength of short range interactions, while DeltaDeltaG(o)K(D) values which include the effects of long range electrostatic forces that alter specifically DeltaDeltaG(double dagger)k(a) were treated separately.

Allosteric Site↗
PubMed2000

[Symptom of micro-orchism for fertility and endocrine testicular function].

BACKGROUND AND OBJECTIVE: There are no reliable findings regarding the frequency and etiology of the spermatogenetic and endocrine functional restrictions in the small testicle (microorchidism). This information is needed to properly assess the risk when multiple testicular biopsies for assisted reproduction techniques lead to further volume reduction. PATIENTS/METHODS: 535 patients consulting our andrological clinic were included into the study. Orchidometric findings were corelated to spermatological data. Furthermore, FSH, Inhibin B, LH, testosterone and 17 estradiol were analysed. In 116 cases extended andrological studies clarified the etiology of the microorchidism. RESULTS: 26.5% of the patients had a testicular volume < or = 12 ml, 67.1% were in the normal area, 6.4% show a testicular volume > 25 ml. Patients with small testicles had azoospermia in 44.6%, OAT-syndrome in 20.2% and endocrine hypogonadism in 19.8%. The most frequent causes were Klinefelter-syndrome, maldescensus testis, varicocele, secondary atrophies and idiopathic clinical pictures. CONCLUSIONS: Microorchidism is understood as a one-sided testicular volume < or = 12 ml in adult men. We consider the risky taking of tissue out of the small testicle as avoidable, if predictive diagnostic factors for the discovering of spermatozoa via operation are analysed. An androgen-substitution in microorchidism may be carried out in selected individuals.

Adult↗
PubMed2000

G protein levels and function as an objective measure of depression in patients with functional bowel disorders.

Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins have been implicated in the pathophysiology, diagnosis, and treatment of mood disorders and proposed as a state-dependent biochemical mood marker in mononuclear leukocytes. Irritable bowel syndrome (IBS) is associated with changes in mood, affecting patients' illness perceptions and behavior. We examined whether mononuclear leukocytes of patients with IBS have altered G protein measures. We undertook G protein functional measurements through agonist-enhanced [3H]Gpp(NH)p binding capacity and quantitative measures by immunoblot analysis using anti-Galpha antibodies in mononuclear leukocytes obtained from 19 IBS patients (Rome criteria) and 19 healthy matched subjects. The study groups were similar in age, gender, and years of education. Mononuclear leukocyte functions of G(s) (21.3+/-8.3%) and G(i) (22.2+/-6.7%) proteins in IBS patients were similar to healthy subjects (24.8+/-4.7 and 25.2+/-4.0%, respectively). The relative immunoreactivities of the G(sa) (98.9+/-10.2%) and the G(ia) (104.2+/-11.5%) subunit proteins in mononuclear leukocytes of IBS patients were also similar to those in healthy subjects. Two patients clinically diagnosed as depressed were detected by the G protein assay. The results lend objective support to the contention that major depression is not a causative factor in IBS, nor associated with its severity. The G protein assay may provide an objective biochemical tool for detecting depression in IBS, differentiating it from psychological distress that is commonly diagnosed by subjective tests.

Adult↗
PubMed2000

Rational design of faster associating and tighter binding protein complexes.

A protein design strategy was developed to specifically enhance the rate of association (k(on)) between a pair of proteins without affecting the rate of dissociation (k(off)). The method is based on increasing the electrostatic attraction between the proteins by incorporating charged residues in the vicinity of the binding interface. The contribution of mutations towards the rate of association was calculated using a newly developed computer algorithm, which predicted accurately the rate of association of mutant protein complexes relative to the wild type. Using this design strategy, the rate of association and the affinity between TEM1 beta-lactamase and its protein inhibitor BLIP was enhanced 250-fold, while the dissociation rate constant was unchanged. The results emphasize that long range electrostatic forces specifically alter k(on), but do not effect k(off). The design strategy presented here is applicable for increasing rates of association and affinities of protein complexes in general.

Algorithms↗
PubMed2000

17 Alpha-oestradiol and 17 beta-oestradiol do not affect basal and follicle-stimulating hormone-stimulated inhibin B secretion by highly purified rat Sertoli cells.

The effects of 17 alpha-oestradiol and 17 beta-oestradiol on basal and follicle-stimulating hormone (FSH)-stimulated inhibin B secretion by rat Sertoli cells were studied. Sertoli cells were isolated and cultivated from testes of 18-day-old Wistar rats in the presence and absence of FSH and different doses of oestrogens. On day 4 of culture, secreted inhibin was measured by enzyme-linked immunosorbent assay. Neither 17 alpha-oestradiol nor 17 beta-oestradiol had any effect on the secreted inhibin level in either the presence or absence of FSH. It is concluded that these oestradiols do not play an essential role in regulatory processes involving inhibin or FSH.

Animals↗
PubMed2000

[Efficiency of conventional glass wool and SpermFertil columns with respect to ROS-reduction, leukocyte reduction, and CASA-generated sperm counts in semen].

OBJECTIVE: Glass wool filtration has proved to be useful to separate motile from defective spermatozoa and leukocytes in semen from patients with oligozoospermia and azoospermia. With regard to that, we set out to investigate the efficiency of two widely used filter systems. MATERIAL AND METHODS: Semen from 10 patients attending the Dept. of Andrology, FSU Jena, were investigated with home-made coarse glass wool filters and SpermFertil columns regarding elimination of reactive oxygen species (ROS) and enrichment of semen with motile and progressive spermatozoa. RESULTS: Filtration with home-made glass wool columns did not affect the percentage of motile spermatozoa but increased that of progressive spermatozoa. The whole cell count was decreased by a third. Leukocytes were reduced by half and ROS by more than half. SpermFertil columns increased the percentage of both motile and progressive spermatozoa and the whole cell count was decreased severely. Leukocytes were eliminated almost completely, as were ROS. CONCLUSIONS: Our results show the higher potential of SpermFertil columns to enrich semen specimens with motile and progressive spermatozoa and to almost completely eliminate leukocytes and ROS in comparison to home-made glass wool columns. However, SpermFertil columns reduce the whole cell count to about 10% of the original cell count.

Adult↗
PubMed2000

The evolution of the thyroid hormone distributor protein transthyretin in the order insectivora, class mammalia.

Thyroid hormones are involved in the regulation of growth and metabolism in all vertebrates. Transthyretin is one of the extracellular proteins with high affinity for thyroid hormones which determine the partitioning of these hormones between extracellular compartments and intracellular lipids. During vertebrate evolution, both the tissue pattern of expression and the structure of the gene for transthyretin underwent characteristic changes. The purpose of this study was to characterize the position of Insectivora in the evolution of transthyretin in eutherians, a subclass of Mammalia. Transthyretin was identified by thyroxine binding and Western analysis in the blood of adult shrews, hedgehogs, and moles. Transthyretin is synthesized in the liver and secreted into the bloodstream, similar to the situation for other adult eutherians, birds, and diprotodont marsupials, but different from that for adult fish, amphibians, reptiles, monotremes, and Australian polyprotodont marsupials. For the characterization of the structure of the gene and the processing of mRNA for transthyretin, cDNA libraries were prepared from RNA from hedgehog and shrew livers, and full-length cDNA clones were isolated and sequenced. Sections of genomic DNA in the regions coding for the splice sites between exons 1 and 2 were synthesized by polymerase chain reaction and sequenced. The location of splicing was deduced from comparison of genomic with cDNA nucleotide sequences. Changes in the nucleotide sequence of the transthyretin gene during evolution are most pronounced in the region coding for the N-terminal region of the protein. Both the derived overall amino sequences and the N-terminal regions of the transthyretins in Insectivora were found to be very similar to those in other eutherians but differed from those found in marsupials, birds, reptiles, amphibians, and fish. Also, the pattern of transthyretin precursor mRNA splicing in Insectivora was more similar to that in other eutherians than to that in marsupials, reptiles, and birds. Thus, in contrast to the marsupials, with a different pattern of transthyretin gene expression in the evolutionarily "older" polyprotodonts compared with the evolutionarily "younger" diprotodonts, no separate lineages of transthyretin evolution could be identified in eutherians. We conclude that transthyretin gene expression in the liver of adult eutherians probably appeared before the branching of the lineages leading to modern eutherian species.

Alternative Splicing↗
PubMed2000

Effects of adjuvant interferon-alpha low-dose therapy in melanoma patients on serum inhibin B.

Because the primary aim of adjuvant therapy for melanoma is not curative, all the possible aspects of quality of life have to be considered. One aspect of increasing importance is fertility. The effect of adjuvant interferon alpha-therapy for malignant melanoma on male fertility has not been systematically investigated. In the present study, twelve male patients with primary cutaneous melanoma (pT3, 4; N0; M0) who were taking adjuvant low-dose interferon alpha2b (3 x 3 mio U/week) for one year were included. Inhibin B--an established marker of male fertility-was measured with an immunosorbent assay before and after one year of interferon alpha-therapy to investigate whether this treatment has any influence on fertility. The results were compared with those from normal controls (n=40). The mean serum inhibin B concentration in melanoma patients before interferon therapy was 225.4 +/- 112.5 pg/mL; after treatment the level was 229.6 +/- 82.0 pg/mL. This difference was not statistically significant (p>0.05). The serum inhibin B concentration in controls was 201.5 +/- 17.1 pg/mL, which was not statistically different from either untreated or interferon-treated melanoma patients (p>0.05). We conclude that low-dose interferon alpha does not have a significant (negative) effect on inhibin B or male fertility.

Adult↗
PubMed2000

Evolution of structure, ontogeny of gene expression, and function of Xenopus laevis transthyretin.

Xenopus laevis transthyretin (xTTR) cDNA was cloned and sequenced. The derived amino acid sequence was very similar to those of other vertebrate transthyretins (TTR). TTR gene expression was observed during metamorphosis in X. laevis tadpole liver but not in tadpole brain nor adult liver. Recombinant xTTR was synthesized in Pichia pastoris and identified by amino acid sequence, subunit molecular mass, tetramer formation, and binding to retinol-binding protein. Contrary to mammalian xTTRs, the affinity of xTTR was higher for L-triiodothyronine than for L-thyroxine. The regions of the TTR genes coding for the NH(2)-terminal sections of the polypeptide chains of TTR seem to have evolved by stepwise shifts of mRNA splicing sites between exons 1 and 2, resulting in shorter and more hydrophilic NH(2) termini. This may be one molecular mechanism of positive Darwinian evolution. Open reading frames with xTTR-like sequences in the genomes of C. elegans and several microorganisms suggested evolution of the TTR gene from ancestor TTR gene-like "DNA modules." Increasing preference for binding of L-thyroxine over L-triiodothyronine may be associated with evolving tissue-specific regulation of thyroid hormone action by deiodination.

Amino Acid Sequence↗