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Biomedical subjects

R Schweitzer

Publications and source records attributed to R Schweitzer.

At least 19 recordsLinked to original sources
PubMed1998

EGF domain swap converts a drosophila EGF receptor activator into an inhibitor.

In Drosophila the function of the epidermal growth factor (EGF) receptor is modulated zygotically by three EGF-like proteins: Spitz (Spi), which is a potent activator; Vein (Vn), which is a moderate activator; and Argos (Aos), which is an inhibitor. Chimeric molecules were constructed in which the EGF domain of Vn was swapped with the EGF domain from each factor. The modified Vn proteins behaved both in vitro and in vivo with properties characteristic of the factor from which the EGF domain was derived. These results demonstrate that the EGF domain is the key determinant that gives DER inhibitors and activators their distinct properties.

Amino Acid Sequence↗
PubMed1998

Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis.

Previous work has demonstrated a role for the Drosophila EGF receptor (Torpedo/DER) and its ligand, Gurken, in the determination of anterioposterior and dorsoventral axes of the follicle cells and oocyte. The roles of DER in establishing the polarity of the follicle cells were examined further, by following the expression of DER-target genes. One class of genes (e.g. kekon) is induced by the DER pathway at all stages. Broad expression of kekon at the stage in which the follicle cells migrate posteriorly over the oocyte, demonstrates the capacity of the pathway to pattern all follicle cells except the ventral-most rows. This may provide the spatial coordinates for the ventral-most follicle cell fates. A second group of target genes (e.g. rhomboid (rho)) is induced only at later stages of oogenesis, and may require additional inputs by signals emanating from the anterior, stretch follicle cells. The function of Rho was analyzed by ectopic expression in the stretch follicle cells, and shown to induce a non-autonomous dorsalizing activity that is independent of Gurken. Rho thus appears to be involved in processing a DER ligand in the follicle cells, to pattern the egg chamber and allow persistent activation of the DER pathway during formation of the dorsal appendages.

Animals↗
PubMed1997

A comparison of masticatory function in patients with or without reconstruction of the mandible.

BACKGROUND: The functional benefits of mandibular reconstruction following a composite resection remain unclear. Although microvascular surgical techniques have dramatically increased the predictability of bone and soft-tissue reconstruction towards presurgical anatomic norms, the specific factors responsible for improved function remain controversial. Objective measures of masticatory function need to be more clearly determined before the predictability and efficacy of reconstructive approaches is established. METHODS: We evaluated objective measures of oral function and patient reports of function in 10 reconstructed mandibulectomy patients, 10 without reconstruction, and 10 controls. Measures of oral function included bite force assessed at the first molar and incisal edge, a measure of tongue and cheek function, and patient reports of food they could eat. RESULTS: Both reconstructed and nonreconstructed patients presented decreased biting force, a more restricted diet, and compromised cheek and tongue function as compared with normals. However, reconstructed patients had significantly better measures of tongue function and ability to eat a varied diet than did nonreconstructed patients. Of the objective measures used to measure masticatory performance, bite force was poorly correlated, whereas measures of tongue function strongly correlated with successful mastication. CONCLUSION: Both reconstructed and nonreconstructed patients presented with a significant functional deficit when compared with normals, with reconstructed patients having better overall function than nonreconstructed patients.

Aged↗
PubMed1997

Plasma carotenoids in German children and adolescents.

UNLABELLED: Carotenoids are important antioxidants and precursors of vitamin A, but only few studies have been carried out on plasma carotenoid levels in paediatric age groups. Using high-performance liquid chromatography we analysed concentrations of four important carotenoids (alpha-carotene, beta-carotene, cryptoxanthin, lycopene) in 129 healthy German children and adolescents (81 boys, 48 girls; age 1-18 years). For all carotenoids analysed, no significant differences between girls and boys were found. alpha-Carotene values ranged from 0 mumol/l (below detection limits) to 0.73 mumol/l (0-395 micrograms/l), beta-carotene from 0.09 mumol/l to 2.68 mumol/l (48-1443 micrograms/l), lycopene from 0 mumol/l to 1.51 mumol/l (0-815 micrograms/l), and cryptoxanthin from 0 mumol/l to 0.30 mumol/l (0-164 micrograms/l), respectively. Data analyses according to age groups showed a tendency towards higher levels of alpha- and beta-carotene, and lower levels of lycopene in young children. These differences were significant when children younger than 4 years were compared with those above 8 and 12 years, respectively. The data presented may serve as reference values for studies on children with nutritional disorders and diseases associated with a risk of vitamin deficiencies. CONCLUSION: Carotenoids are important antioxidants and singlet oxygen scavengers. Plasma levels of alpha-carotene, beta-carotene, lycopene and cryptoxanthin were determined in 129 healthy German children and adolescents. Highest values were found for beta-carotene and lycopene.

Adolescent↗
PubMed1997

A thousand and one roles for the Drosophila EGF receptor.

In the Drosophila genome there is a single member of the EGF receptor tyrosine kinase family. This receptor fulfills multiple roles during development, as reflected by the many designations given to mutant alleles in the locus (Egfr, DER, faint little ball, torpedo and Ellipse). The full scope of EGFR functions became apparent only in recent years: receptor activation was shown to have an instructive role in successive cell fate determination events during oogenesis, embryogenesis, and the proliferation and differentiation of imaginal discs. To ensure the fidelity of these processes, the precise place and time of receptor activation are tightly regulated by the localized presentation of activating ligands, in conjunction with a negative-feedback loop generated by an inhibitory secreted factor. The cellular mechanisms that translate EGFR activation to discrete cell fates are now the focus of intense studies.

Animals↗
PubMed1996

Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop.

Argos is a secreted molecule with an atypical EGF motif. It was recently shown to function as an inhibitor of the signaling triggered by the Drosophila EGF receptor (DER). In this work, we determine the contribution of Argos to the establishment of cell fates in the embryonic ventral ectoderm. Graded activation of DER is essential for patterning the ventral ectoderm. argos mutant embryos show expansion of ventral cell fates suggesting hyperactivation of the DER pathway. In the embryonic ventral ectoderm, argos is expressed in the ventralmost row of cells. We show that argos expression in the ventral ectoderm is induced by the DER pathway: argos is not expressed in DER mutant embryos, while it is ectopically expressed in the entire ventral ectoderm following ubiquitous activation of the DER pathway. argos expression appears to be triggered directly by the DER pathway, since induction can also be observed in cell culture, following activation of DER by its ligand, Spitz. Argos therefore functions in a sequential manner, to restrict the duration and level of DER signaling. This type of inhibitory feedback loop may represent a general paradigm for signaling pathways inducing diverse cell fates within a population of non-committed cells.

Animals↗
PubMed1995

Inhibition of Drosophila EGF receptor activation by the secreted protein Argos.

The Drosophila homologue of the mammalian epidermal growth factor (EGF) receptor (DER) is a receptor tyrosine kinase involved in many stages of fly development, including photoreceptor determination, and wing-vein formation. Its primary activating ligand is the Spitz protein, which is similar to mammalian TGF-alpha. Argos is a secreted protein that, like Spitz, contains a single EGF motif. It is a repressor of cell determination in the eye, and acts in other tissues, including the wing. Because Argos has the opposite effects to DER in the eye (the former blocks photoreceptor determination, the latter promotes it) we have tested whether it acts by blocking the DER pathway. We show that Argos does indeed repress this pathway in vivo and find that, in vitro, Argos protein can inhibit the activation of DER by Spitz. Thus the determination of cells by the DER pathway is regulated by a balance between extracellular activating and inhibiting signals. This is the first in vivo example of an extracellular inhibitor of a receptor tyrosine kinase.

Animals↗
PubMed1995

Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination.

The spitz gene encoding a TGF-alpha homolog, has been shown to affect a subset of developmental processes that are similar to those regulated by DER, the Drosophila EGF receptor homolog. This work demonstrates that Spitz triggers the DER signaling cascade. Addition of a secreted, but not the membrane-associated form of Spitz to S2 Drosophila cells expressing DER gives rise to a rapid tyrosine autophosphorylation of DER. Following autophosphorylation, DER associates with the Drk adapter protein. Consequently, activation of MAP kinase is observed. The profile of MAP kinase activation provides a quantitative assay for DER activation. A dose response between the levels of Spitz and MAP kinase activity was observed. The secreted Spitz protein was expressed in embryos to assess its biological activity. An alteration in cell fates was observed in the ventral ectoderm, such that lateral cells acquired the ventral-most fates. The result indicates that graded activation of the DER pathway may normally give rise to a repertoire of discrete cell fates in the ventral ectoderm. Spatially restricted processing of Spitz may be responsible for this graded activation. The Rhomboid (Rho) and Star proteins were suggested, on the basis of genetic interactions, to act as modulators of DER signaling. No alteration in DER autophosphorylation or the pattern of MAP kinase activation by secreted Spitz was observed when the Rho and Star proteins were coexpressed with DER in S2 cells. In embryos mutant for rho or Star the ventralizing effect of secreted Spitz is epistatic, suggesting that Rho and Star may normally facilitate processing of the Spitz precursor.

Animals↗
PubMed1995

Quality of life in chronic fatigue syndrome.

Whilst the debilitating fatigue experienced in patients suffering from Chronic Fatigue Syndrome (CFS) results in a subjective marked impairment in functioning, little research has investigated the impact of this disorder on quality of life. Forty-seven subjects with a confirmed diagnosis of CFS and 30 healthy controls were compared using the Sickness Impact Profile (SIP). A subgroup of subjects were interviewed regarding the impact CFS has had on their social and family relationships, work and recreational activities. Results from both the SIP and the interview revealed that CFS subjects had significantly impaired quality of life, especially in areas of social functioning. These findings highlight the importance of addressing the social isolation and loss of role functioning experienced by CFS sufferers.

Adaptation, Psychological↗
PubMed1995

Suicidal ideation and behaviours among university students in Australia.

OBJECTIVE: The aim of the study was to investigate the prevalence and demographic correlates of suicidal ideation and behaviours among university students in Australia and the utilisation of mental health services by this population. METHOD: Suicidal ideation and behaviours and demographic variables were assessed in a population of 1,678 undergraduate students by use of a modified Suicide Ideation Scale (SIS) and questionnaire. RESULTS: Sixty two percent of students surveyed showed some suicidal ideation and 6.6% reported one or more suicide attempts. Over half of the group who reported suicide attempts did not use any type of mental health services. Suicidal ideation was found to be highly correlated with previous use of mental health services. In examining the relationship between suicidal ideation (SI) and demographic variables, SI was not significantly different for gender or parental marital status but was related to living arrangements, racial groups, religious affiliation and father's education. CONCLUSIONS: The results suggest that a higher proportion of students reported suicidal ideation and behaviours than that documented in related studies undertaken in the USA. While these findings draw attention to a higher level of suicidal ideation in students who utilise mental health assistance, more than half of those who reported suicide attempts did not use any kind of mental health service. The study has particular implications for detecting and assisting young people with a high suicide risk within the university environment.

Adolescent↗
PubMed1994

Illness behaviour of patients with chronic fatigue syndrome.

The study examines the illness behaviour of patients with Chronic Fatigue Syndrome (CFS). The Illness Behaviour Questionnaire (IBQ), the twenty-eight version of the General Health Questionnaire (GHQ-28), and the Beck Depression Inventory (BDI) were administered to forty patients with a diagnosis of CFS. The results revealed that CFS patients in comparison with general practice patients, scored significantly higher on the IBQ sub-scales of General Hypochonriasis, t(188) = 5.2, p < 0.001 and Disease Conviction, t(188) = 13.28, p < 0.001 but lower on the Psychological/Somatic sub-scale, t(188) = -5.88, p < 0.001. The CFS and psychiatric patients did not differ significantly on the general hypochondriasis sub-scale. Results of the GHQ-28 revealed 66.7% of the CFS patients scored above the cut-off for psychiatric morbidity. In comparison to a previous study of CFS patients [1], the current findings indicate a significantly higher score on general hypochondriasis. The implications of these findings are discussed.

Adult↗
PubMed1994

Scattered-site crisis beds: an alternative to hospitalization for children and adolescents.

This paper describes the rationale, development, and implementation of a countywide scattered-site crisis bed program for seriously emotional disturbed youngsters. The program was developed by an interagency coalition consisting of representatives of the county's mental health, social service, and juvenile justice systems and was implemented with no new funding using available beds in facilities administered by the participating agencies. Referrals are screened by an interagency crisis consultation team responsible for the program's operation. A computerized registry significantly reduces the amount of time needed to make placements and helps agencies meet the goal of placing youngsters on the day of referral. Evaluation of the first 100 placements indicated that the program is a cost-effective alternative to more restrictive, longer-term placements and has resulted in positive clinical outcomes.

Adolescent↗
PubMed1994

Tachycardia and panic attacks.

This case taught me the importance of listening closely to the patient's history, and not just jumping in and accepting an old diagnosis. It also showed me how patients can effect change in their lives, that even when patients are seemingly crippled by panic, anxiety, stress, and with a history of sexual abuse as a child, that person can effect meaningful change in their life and reclaim their life from the effects of these problems.

Adult↗
PubMed1993

Difficulties in treating one's family.

Thinking of treating your family?--think again! There are risks involved as objectivity is in danger of being clouded by emotions. Guidelines for the 'family' doctor are drawn from the author's experience.

Anecdotes as Topic↗
PubMed1992

Breast cancer incidence in women with abnormal cytology in nipple aspirates of breast fluid.

This is a prospective study of breast cancer risk in relation to nipple aspirate fluid cytology in 2,701 volunteer white women from the San Francisco Bay Area first enrolled between 1973 and 1980. The women were not pregnant or lactating and were free of breast cancer within 6 months of entry into the study. The breast cancer status of this cohort was determined between June 1988 and April 1991. Follow-up was complete for 87% (n = 2,343) of the cohort, representing 29,961 person-years and an average of 12.7 years of follow-up. The overall breast cancer incidence was 4.4% (104 of 2,343) and rose with fluid cytology findings as follows: no fluid obtained, 2.6% (9 of 352); unsatisfactory specimen, 4.8% (15 of 315); normal cytology, 4.3% (56 of 1,291); epithelial hyperplasia, 5.5% (18 of 327); and atypical hyperplasia, 10.3% (6 of 58). Relative risks for breast cancer and their 95% confidence intervals were estimated by Cox regression, adjusting for age and year of entry. Compared with the relative risk for women who yielded no fluid, relative risks were: unsatisfactory specimen, relative risk (RR) = 1.4 (95% confidence interval (CI) 0.6-3.3); normal cytology, RR = 1.8 (95% CI 0.9-3.6); epithelial hyperplasia, RR = 2.5 (95% CI 1.1-5.5); and atypical hyperplasia, RR = 4.9 (95% CI 1.7-13.9). These findings were strongest for and were mainly confined to women aged 25-54 years. Women with atypical hyperplasia and a first-degree family history of breast cancer were six times more likely to develop breast cancer than were women with atypical hyperplasia but without a family history of breast cancer (95% CI 1.0-30.2). These findings provide strong support for our hypothesis that hyperplasia and atypical hyperplasia diagnosed in nipple aspirates of breast fluid are associated with an increased risk of breast cancer.

Adolescent↗
PubMed1992

Parent and adolescent perceptions of family functioning: a comparison of clinic and non-clinic families.

In this paper two studies are reported which compare (a) the perceptions of family functioning held by clinic and non-clinic adolescents, and (b) the perceptions of family functioning held by adolescents and their mothers in clinic and non-clinic families. In Study 1, matched group of clinic and non-clinic adolescents were compared on their responses to a 30-item scale (ICPS) designed to measure three factors of family functioning: Intimacy (high vs. low), Parenting Style (democratic vs. controlled) and Conflict (high vs. low). Clinic and non-clinic adolescents were also compared on their responses to a multi-dimensional measure of adolescent self-concept. Although there was little difference between the two groups of adolescents in terms of their perceptions of family functioning, there were strong relationships between the self-concept variables and the family functioning variables. In Study 2, comparisons were made between the perceptions of family functioning held by mothers and adolescents for both clinical and non-clinic families. There were no differences between the two groups of adolescents in terms of their perceptions of family functioning, although there were clear differences between the two groups of mothers. In addition, clinic adolescents and their mothers did not differ in their perceptions of the family, whereas adolescents in the non-clinic group saw their families significantly as less intimate and more conflicted than did their mothers.

Adolescent↗