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Biomedical subjects

G Wolff

Publications and source records attributed to G Wolff.

At least 37 records · Page 2Linked to original sources
PubMed1999

A descriptive analysis of factors contributing to binge eating.

This study was designed to examine temporally proximal and remote antecedents as well as immediate and delayed consequences of binge eating behavior. Participants included 16 undergraduate females who reported engaging in binge eating at least two times per week and experiencing a sense of lack of control during binge eating episodes on the Questionnaire of Eating and Weight Patterns. Results indicated that the most frequent proximal antecedents to binge eating were negative emotions such as feeling depressed, angry, empty, hopeless, worried, or dissatisfied. The most frequent consequences of binge eating included relief from negative feelings and thoughts and decrease in hunger or craving. The results of this study suggest that the function of binge eating can be identified through assessment of antecedents and consequences with real time recording and retrospective reports. Treatment implications are discussed.

Adult↗
PubMed1999

Analysis of the p53/BAX pathway in colorectal cancer: low BAX is a negative prognostic factor in patients with resected liver metastases.

PURPOSE: To determine the prognostic value of the central downstream apoptosis effector BAX in relation to its upstream regulator p53 in R0-resected hepatic metastases of colorectal cancer. PATIENTS AND METHODS: Retrospective analysis of 41 patients who underwent potentially curative resection of liver metastases from colarectal cancer was performed. Tumor DNA was screened for p53 mutations by single-stranded conformational polymorphism polymerase chain reaction and for BAX frameshift mutations by fragment length analysis. Protein expression of BAX, p21, and p53 was investigated by immunohistochemistry. RESULTS: Overall median survival was 40.2 months. Tumors with BAX frameshift mutations were considered microsatellite mutator phenotype-positive and were excluded from further prognostic analyses. Patients with high BAX protein expression had a median survival of 53.6 months compared with 35.4 months for patients with low BAX expression (P < .05). The negative prognostic value of low BAX expression was more evident in those patients with wild-type p53 (median survival, 54.0 v 23.3 months for BAX-negative tumors; P < .01). Low BAX expression was an independent negative prognostic marker in multivariate regression analysis for all patients independent of the p53 status (relative risk, 3.03, P = .03), especially for p53 wild-type tumors (relative risk, 8.21; P = .0095). CONCLUSION: We conclude that low BAX expression is an independent negative prognostic marker in patients with hepatic metastases of colorectal cancer. The best survival was seen in patients with an intact p53-to-BAX pathway; ie, wild-type p53- and BAX-positive tumors. Thus, analysis of apoptosis signaling pathways (here, p53 in concert with its downstream death effector, BAX) might yield more prognostic power in future studies as compared with analysis of single genes such as p53 alone.

Adult↗
PubMed1999

An investigation of shame and guilt in a depressed sample.

A self-report measure of proneness to shame and guilt was administered to 86 patients with moderate to severe depression, with the prediction that there would be a positive correlation of shame with severity of depression. Contrary to other, non-clinical studies, we found that guilt but not shame was associated with levels of depression. Shame-proneness demonstrated a unique association with a stable attributional style for negative outcomes, global negative self-evaluation, submissive behaviour and internalized anger. Contrary to prediction, no relationship was found between shame- or guilt-proneness and a reported history of childhood sexual abuse.

Adult↗
PubMed1998

Ex vivo breast cancer cell purging by adenovirus-mediated cytosine deaminase gene transfer and short-term incubation with 5-fluorocytosine completely prevents tumor growth after transplantation.

Peripheral blood progenitor harvests of breast cancer patients are contaminated with tumor cells, suggesting a potential role for these cells in the relapse after high-dose chemotherapy. Whereas physical purging methods do not eliminate contaminating tumor cells completely, pharmacological purging, although highly efficient, is hampered by a strong nonspecific toxicity toward hematopoietic progenitor cells. Taking advantage of the high efficiency of adenovirus-mediated gene transfer to epithelial cells, we selectively loaded breast cancer cells in vitro with a cytotoxic drug by gene transfer of the prodrug-converting enzyme cytosine deaminase (AdCMV.CD) and 5-fluorocytosine (5-FC). Despite the low dose of vector administered, limited exposure to 5-FC, and transplantation only of viable tumor cells into SCID mice, all animals that received cells treated in vitro with AdCMV.CD plus 5-FC were completely free of tumor development. These data show that the selective loading of tumor cells with AdCMV.CD/5-FC might be useful for purging of autografts.

Adenoviridae↗
PubMed1998

Non-compliance following renal transplantation in children and adolescents.

Reported frequencies of non-compliance in children with end-stage renal disease range from 8% to 70% with a mean around 40%. Sequelae amount to momentous emotional and financial burdens, including the loss of 7% of transplanted organs. Reasons for non-compliance have too often been attributed selectively to the patients (e.g., emotional, mental, social, or communication problems). Compared with general compliance research, this selective attribution appears to be too simplistic. Selective attribution neglects the patients' experiences within the context of disease and treatment and prevents open communication about non-compliance. Research on personal reasons for non-compliance is scarce. In psychological interviews, a third of our 85 patients with end-stage renal disease (34 boys, 51 girls, mean age 12.7 years, range 7.4-19.3 years) communicated psychologically meaningful reasons for non-compliance, frequently related to interrelational and systemic treatment conditions. Patients indirectly asked for more communication about their subjective reasons for non-compliance.

Adolescent↗
PubMed1997

Role of alveolar macrophages in rapid elimination of adenovirus vectors administered to the epithelial surface of the respiratory tract.

To evaluate the hypothesis that innate immune mechanisms play a major role in eliminating adenovirus (Ad) vectors from the lung, the fate of adenoviral genome of an Ad vector was quantified in the first 24 h after intratracheal administration of an Ad vector coding for beta-galactosidase (beta gal) to mice. Southern analysis with an Ad specific probe showed that 70% of the Ad genome was lost within 24 h, in both immunocompetent and immunodeficient animals. When alveolar macrophages were eliminated by administration of liposomes containing dichloromethylene-biphosphanate, subsequent administration of Ad vector was associated with a 100%+/-8% increase in lung Ad DNA and 96%+/-9% rise in beta gal expression at 24 h compared to control animals. In vitro infection of mouse, rat, and human alveolar macrophages with an Ad vector resulted in 65% loss of vector genome within 24 h, whereas the vector genome was stable in lung epithelial cell lines. PCR in situ hybridization demonstrated that the Ad vector genome persisted A549 lung epithelial cell in vitro but not in alveolar macrophages. Finally, alveolar macrophages recovered from the mouse lung 30 min following intratracheal administration of an Ad vector showed large amounts of vector genome, whereas much less was evident in alveolar macrophages recovered after 24 h. These observations demonstrate that alveolar macrophages play an important role in elimination of Ad vectors from the lung and suggest that strategies to transiently suppress this major innate immune defense system might be rewarding in enhancing the efficiency Ad vectors for lung gene therapy.

Adenoviridae↗
PubMed1997

[The importance of counseling in the context of prenatal diagnosis].

Counseling plays a central role of the utmost importance in the doctor-patient/client relationship in medical genetics. Historically, its development may be described as a paradigm shift from eugenics via preventive medicine to a more psychosocial understanding as a communication process, which aims at individually bearable, autonomous decisions. The widely accepted conception of non-directiveness in genetic counseling has implications for the rights of patients and clients as well as for the duties of those offering and performing genetic diagnosis and counseling. In the context of prenatal diagnosis, genetic counseling has its special role as a framework to prevent ethically unacceptable automatism and to safeguard the interests of the individual patient/client. In view of the marked lack of adequate counseling capacities, increasing the potential of prenatal genetic diagnosis requires the development of different, possibly new concepts for counseling in this area.

Abortion, Induced↗
PubMed1997

Innate immune mechanisms dominate elimination of adenoviral vectors following in vivo administration.

To evaluate the contribution of the innate immune component of host defense in clearing the genome of adenovirus (Ad) vectors following in vivo administration, the Ad vectors AdCMV.beta gal (expressing beta-galactosidase) or AdCMV.Null (expressing no gene) were administered intravenously to immunocompetent or immunodeficient mice, and the amount of vector genome was quantified in the liver. Strikingly, 90% of vector DNA was eliminated within 24 hr. There was no increase in vector DNA in other tissues over this period, suggesting that rapid clearance of vector genome resulted from local degradation. After 24 hr, vector elimination was slow, with only 9% of the initial amount of vector genome cleared over the subsequent 3 weeks. Importantly, early phase (0-24 hr) elimination of vector DNA was independent of the transgene and similar in immunocompetent and nude animals. These observations suggest two phases of Ad vector elimination: a previously recognized late, immune-related elimination, and the early, innate immune elimination described in the present study. The early phase of vector loss is, by far, the dominant mechanism, an observation that has implications in developing strategies to maintain persistent expression of the newly transferred gene following in vivo gene therapy.

Adenoviridae↗
PubMed1997

Localization of the gene for Wieacker-Wolff syndrome in the pericentromeric region of the X chromosome.

The Wieacker-Wolff syndrome (WWS, MIM* 314580), first described clinically in 1985, is an X-linked recessive disorder. In earlier studies, linkage between the WWS gene and DXYS1 at Xq21.2 and DXS1 at Xq11 as well as AR at Xq12 was reported. Here we report on a linkage analysis using highly polymorphic, short terminal repeat markers located in the segment from Xp21 to Xq24. No recombination between the WWS locus and ALAS2 or with AR (z = 4.890 at theta = 0.0) was found. Therefore, the WWS locus was assigned to a segment of approximately 8 cM between PFC (Xp11.3-Xp 11.23) and DXS339 (Xq11.2-Xq13).

Centromere↗
PubMed1997

Rare combination of Becker muscular dystrophy and Klinefelter's syndrome in one patient.

Becker muscular dystrophy (BMD) was diagnosed in a male patient with Klinefelter's syndrome (47, XXY karyotype). The BMD was confirmed by (i) immunohistological methods and Western blotting, showing decreased quantity of dystrophin in muscle biopsy specimen and (ii) molecular genetic analysis which demonstrated a homozygous deletion of exons 45-47 within the dystrophin gene on both X-chromosomes. The same deletion was found on one of the X-chromosomes in the patient's mother. It can be deduced therefore that Klinefelter's syndrome in this patient is most likely due to a non-disjunctional error which occurred either during the second maternal meiotic division or during early postzygotic mitotic divisions.

Adult↗
PubMed1997

Enhancement of in vivo adenovirus-mediated gene transfer and expression by prior depletion of tissue macrophages in the target organ.

Based on the hypothesis that tissue macrophages present an obstacle for adenovirus (Ad) vector-mediated gene transfer to internal organs, this study evaluated the consequences of transient depletion of Kupffer cells on subsequent transfer of the Ad vector genome and Ad vector-directed gene expression in the livers of experimental animals. Depletion of Kupffer cells in mice by intravenous administration of multilamellar liposomes containing dichloromethylene-bisphosphonate permitted subsequent intravenous administration of an Ad vector to provide a higher input of recombinant adenoviral DNA to the liver, an absolute increase in transgene expression, and a delayed clearance of the vector DNA and transgene expression. These observations suggest that the tissue macrophages pose a significant hurdle to Ad vector-mediated gene transfer and that strategies to transiently suppress macrophage defenses might be useful in enhancing the efficiency of this in vivo gene transfer system.

Adenoviruses, Human↗
PubMed1996

Isochromosome Xq in Klinefelter syndrome: report of 7 new cases.

In this collaborative study we report on 2 prenatally and 5 postnatally diagnosed cases with a 47,X,i(Xq),Y chromosomal constitution. Excepting tall stature, the 5 adult patients showed all typical manifestations of Klinefelter syndrome. Taken together with previously reported cases, these data suggest that Klinefelter syndrome with isochromosome Xq has a favorable prognosis with normal mental development, and with normal-to-short stature. The prevalence of this Klinefelter variant is calculated to be between 0.3-0.9% in males with X chromosome polysomies.

Adult↗
PubMed1996

Severe mental retardation and macroorchidism without mutation in the FMR1 gene.

Only one missense mutation, an Ile304Asn, has been reported in the fragile X gene (FMR1). This mutation is located in the second KH domain of FMR1, and has led to the discovery of the function of the FMR1 gene product as an RNA-binding protein. The patient carrying this mutation has profound mental retardation, macroorchidism, and an "acromegalic" face with prominent supraorbital ridges, enlarged jaw, heavy brow ridges, thick lips, and a broad nose. We have studied the possible involvement of FMR1 in two maternal half-brothers with a phenotype similar to that of the patient with the Ile304Asn mutation. Both brothers had an identical number of CGG repeats in the normal size-range, and shared the same maternal Xq27 haplotype. Southern blot analysis with two overlapping FMR1 cDNA clones, spanning the total FMR1 open reading frame, showed no major deletions, insertions, or gross rearrangements. Single-strand conformation pattern (SSCP) analysis of the KH domains showed no aberrant patterns. The total open reading frame of the FMR1 gene was cloned and sequenced, but no mutation was found. Northern blot analysis showed mRNA in the normal size-range, and immunocytochemistry on individual lymphocytes indicated that FMRP, the protein product of FMR1, was present. In conclusion, it is unlikely that FMR1 plays a role in the phenotype of this patient. Other genes may be responsible for the combination of mental retardation and macroorchidism.

Abnormalities, Multiple↗
PubMed1996

Transcript mapping and processing of mitochondrial RNA in the chlorophyte alga Prototheca wickerhamii.

The detailed transcript map of the circular 55328 bp mitochondrial (mt) genome from the colourless chlorophycean alga Prototheca wickerhamii has been determined. On each half of this genome the genes are encoded only on one DNA strand, forming transcriptional units comprising variable numbers of genes. With the exception of four genes coding for ribosomal proteins, transcripts of the three rRNA genes and all protein-coding genes have been detected by both northern analysis and primer extension experiments. Polycistronic transcripts of protein coding and tRNA genes were verified by northern analyses, primer extension and RNAse mapping experiments. The 5' and 3' ends of different RNA species are often located in close proximity to putative stem-loop structures and some 5' termini of mRNAs coincide with the 3' end of tRNAs located immediately upstream. Transcript mapping in a putative promoter region revealed two different possible transcription initiation sites; no significant sequence homology to putative mt promoters from higher plants could be found. In addition, two out of three group I introns residing in the cox1 gene were found to be self-splicing in vitro under reaction conditions developed for related mt introns from a filamentous fungus. Mitochondrial gene expression of P. wickerhamii and of filamentous fungi has several features in common, such as intron splicing and the processing of longer polycistronic transcripts. The similarities in RNA maturation between higher-plant and P. wickerhamii mitochondria are less pronounced, since plants rarely use tRNAs as processing signals for their relatively short mitochondrial co-transcripts.

Base Sequence↗
PubMed1996

Ectopic expression of thyrotropin releasing hormone (TRH) receptors in liver modulates organ function to regulate blood glucose by TRH.

Maintenance of blood glucose by the liver is normally initiated by extracellular regulatory molecules such as glucagon and vasopressin triggering specific hepatocyte receptors to activate the cAMP or phosphoinositide signal transduction pathways, respectively. We now show that the normal ligand-receptor regulators of blood glucose in the liver can be bypassed using an adenovirus vector expressing the mouse pituitary thyrotropin releasing hormone receptor (TRHR) cDNA ectopically in rat liver in vivo. The ectopically expressed TRHR links to the phosphoinositide pathway, providing a means to regulate liver function with TRH, an extracellular ligand that does not normally affect hepatic function. Administration of TRH to these animals activates the phosphoinositide pathway, resulting in a sustained rise in blood glucose. It should be possible to use this general strategy to modulate the differentiated functions of target organs in a wide variety of pathologic states.

Adenoviridae↗