Hamartoma affecting ampullary electroreceptors and epitheliotropic lymphoma in a captive electric eel Electrophorus varii.

Few reports are available describing lesions in captive electric eels Electrophorus spp. This report describes 2 types of cutaneous proliferative lesions (i.e. hamartoma and neoplasm) in a captive electric eel. Ampullary electroreceptor hamartomas appeared grossly as 2 discrete, smooth, pink, spherical, cutaneous masses measuring 6 and 18 mm in diameter. Histologically, hamartomas were composed of predominately spindle cells that were separated into lobules by a peripheral rim of polygonal cells. Spindle cells were arranged in vague streams and occasionally whorls within a myxomatous matrix. Polygonal cells arranged in variably sized trabeculae and cords within a pre-existing fibrovascular stroma surrounded the streams of spindle cells. Admixed with the polygonal cell population were multiple mucous glands and alarm cells, similar to those seen in normal regions of epidermis. Histochemical stains confirmed similar components in the normal ampullary electroreceptor as in the hamartomas. Lymphoma was also present, appearing grossly as patchy pitting, erythematous, and thickened areas of the skin affecting the entire animal. Lymphoma was diffusely infiltrating and expanding the epidermis, oral mucosa, and branchial mucosa up to 1.5 mm in thickness. It was composed of an unencapsulated, well-demarcated, moderately cellular neoplasm composed of lymphocytes arranged in small dense sheets and clusters that separated and effaced epidermal cells. This is the first report of lymphoma in an electric eel, and the first report of ampullary electroreceptor hamartoma in any animal species.

Endocardiosis in Tetras (Family Characiformes).

Proliferative, myxomatous change was identified in the cardiac valves (i.e. valvular endocardiosis) with extension into some cardiac walls (i.e. mural endocardiosis) of five tetras (four neon tetras [Paracheirodon innesi] and one rummynose tetra [Hemigrammus rhodostomus]). Review of cardiac sections from tetras (family Characiformes) submitted to two diagnostic laboratories revealed a prevalence of endocardiosis in tetras of 4.3% and 5.7%, respectively. In four cases, concurrent disease that could be a primary cause of death was not identified, and endocardiosis was considered the primary cause of death; in the fifth case, egg binding was present concurrently. This retrospective case series suggests that endocardiosis is a significant concern in fish of the family Characiformes.

Graft-versus-leukaemia effect post fludarabine, melphalan and alemtuzumab reduced intensity allogeneic stem cell transplantat in HIV-infected patient with acute myeloid leukaemia.

Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high-risk acute myeloid leukaemia (AML). In spite the advent of highly active antiretroviral treatment, HIV-infected patients display a remarkable risk for haematological neoplasms such as non-Hodgkin lymphomas, Hodgkin lymphoma and acute leukaemia. Several case series have confirmed the efficacy of the autologous stem cell transplantation for the treatment of non-Hodgkin lymphomas in the HIV setting. Nonetheless, there is a paucity of data for the role of the Allo-HSCT in HIV-infected individuals with haematological malignancies. Herein, we presented the successful long-term outcome of a HIV-infected patient who received reduced intensity conditioned, matched unrelated donor transplant with alemtuzumab as graft-versus-host disease prophylaxis for therapy-related acute myeloid leukaemia. We propose that Allo-HSCT in HIV patients is safe and that alemtuzumab-based conditioning could further work to eradicate HIV in those whose donor is not CCR5 homozygous.

Influence of the serum levels of immunoglobulins on clinical outcomes in medical intensive-care patients.

INTRODUCTION: Endogenous immunoglobulins (Igs) are of fundamental importance in the host defense after microbial infections. However, the therapeutic administration of intravenous IgG (IVIgG) has not yet been shown to improve clinical outcomes in patients suffering from sepsis, and in the case of IgM-containing preparations (IVIgGMA) the positive evidence is only weak. Recently published studies implicate that Ig levels on admission could have an impact on the patient's response to IVIg treatment and on outcomes of critically ill patients. METHODS: In this noninterventional study, the serum levels of IgG, IgM, and IgA were determined in 340 medical patients on ICU admission, and clinical outcomes were prospectively recorded (ICU mortality, need for renal replacement therapy (RRT), need for mechanical ventilation, substitution of coagulation factors, and amount of red cell transfusions). Patients were prospectively grouped according to their main reason for ICU admission (sepsis, respiratory failure, cardiovascular diseases, acute renal failure, postoperative condition, state after cardiopulmonal resuscitation, gastrointestinal diseases, and others). RESULTS AND DISCUSSION: There was no correlation between the Ig levels on admission and ICU mortality neither in the total cohort of medical ICU patients nor in any prespecified subgroup. However, in a logistic regression model that was adjusted for APACHE II score on admission, an increase in serum IgG was associated with a reduced need for mechanical ventilation in patients suffering from cardiovascular disease. On the other hand, in patients suffering from sepsis, an increased level of IgM was linked to an increased administration of coagulation factors. CONCLUSION: Our data do not support the hypothesis that serum levels of immunoglobulins are linked to mortality in medical ICU patients.

Lung protective ventilation and hospital survival of cardiac intensive care patients.

OBJECTIVE: To detect connections between parameters of ventilation and outcomes of cardiac intensive care patients. DESIGN AND SETTING: Noninterventional study. Between 05/11 and 05/12 all patients with acute heart failure and post cardiopulmonary resuscitation were registered. Lung protective ventilation was defined as peak inspiratory pressure (PIP) < 30 mmHg and tidal volume (Vt) < = 6 ml/kg. RESULTS: In total, 129 patients were included in the study, 68.2 % male, age 67.9 ± 13.4 years, weight 71.4 ± 37.2 kg, predictive body weight 66.9 ± 8.8 kg, mortality 47.3 %. Lung protective ventilated patients at day 1: 17.3 % with a significant difference between surviving and nonsurviving patients (24.1 % vs. 9.6 %; p < 0.05). Logistic regression models showed a strong connection between PIP and survival (odds ratio 1.13; p < 0.05). Vt showed no significant influence on survival. CONCLUSION: Our data recommends a strict observance of a low PIP for cardiac intensive care patients, whereas Vt seems to be of secondary importance.

Qualitative needs assessment: healthcare experiences of underserved populations in Montgomery County, Virginia, USA.

INTRODUCTION: Portions of Montgomery County, Virginia, are designated a Medically Underserved Area with a large portion of this population experiencing limited access to healthcare services. In September 2008, the Federal Bureau of Primary Care awarded the authors a planning grant to assess community need in Montgomery County and to develop a strategic plan to establish a Federally Qualified Health Center (FQHC) to best meet these needs. An FQHC is a federally funded clinic mandated to provide medical, dental and mental health services to underserved communities. As part of the planning process, the decision was made to include qualitative data to better understand the needs of underserved residents in the community. Descriptive studies of target populations can provide further insight into community priorities for effective health improvement and planning. The objective of the study was to investigate and describe the perceptions, beliefs and practices that impact healthcare utilization among underserved populations in Montgomery County, Virginia. This study was conducted as part of a comprehensive community assessment to determine the feasibility of developing a FQHC. METHODS: Community focus groups were conducted with target populations which were representative of the community. A thematic analysis of the transcribed field notes and group interviews was conducted. Qualitative data analysis was performed using the Analysis Software for Word-Based Records (AnSWR) developed by the Centers for Disease Control. RESULTS: Three important categories of beliefs which may impact healthcare utilization emerged from the discussions: (1) cultural health perceptions; (2) perceived barriers to care; and (3) coping strategies. Participants expressed a right to access quality care, preferred to spend money on basic living expenses rather than healthcare services; frequently neglected seeking care for adults while rarely neglecting to seek care for their children; valued but infrequently utilized preventative care; and had a lack of confidence in the care that was provided. Perceived barriers to healthcare services reported by participants included a lack of access to affordable care; complexities of health insurance and payer status; limited hours of clinic operation; lack of transportation and geographic distance; and the complexity of navigating the healthcare system. Finally, participants reported using various coping strategies to overcome barriers to accessing healthcare services. These strategies included delaying treatment and self-care; seeking financial and transportation assistance; and using community resources to navigate the system. CONCLUSION: Establishing care that is culturally relevant, targets perceived barriers and incorporates and enhances coping strategies is needed to increase accessibility and utilization of preventative and comprehensive healthcare services. The findings from this study will assist in creating a strategic plan for a FQHC that capitalizes on community strengths while addressing the challenges and complex needs of the community.

Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

Midazolam in conjunction with local anaesthesia is superior to Entonox in providing pain relief during bone marrow aspirate and trephine biopsy.

AIM: To compare intravenous titrated midazolam 5-10 mg and inhaled Entonox in addition to local anaesthesia in order to identify which agent provides optimum pain relief. METHODS: Randomised, controlled trial. 49 patients were recruited, of which 46 were evaluable. 24 and 22 patients were recruited into the Entonox and midazolam arms, respectively. Patient experiences as well as staff observations were recorded with questionnaires after recovery from the procedure and 24 hours later. RESULTS: 45% and 59% of the patients in the midazolam arm could recollect the procedure after 15 minutes and 24 hours, respectively, compared to 96% and 88% who received Entonox. Midazolam provided a more comfortable experience (p<0.01) and improved pain relief (p = 0.01) compared to Entonox immediately after the procedure; this further improved when recalled 24 hours later. Nausea, dizziness and hallucinations were observed with both treatments, but dizziness was significantly more frequent with Entonox (p = 0.048). Clinically relevant respiratory depression (O(2) saturation <90%) occurred in 19% of patients in the midazolam arm; sedation was reversed with flumazenil. CONCLUSION: Midazolam in conjunction with local anaesthesia provides rapid and reversible sedation as well as effective pain relief during bone marrow biopsy, and is superior to Entonox; however, care must be taken to monitor respiratory function.

Endothelial NO-synthase intron 4 polymorphism is associated with disturbed in vivo nitric oxide production in individuals prone to type 2 diabetes.

Insulin resistance, as well as vascular disease, both share a relevant genetic background taking the influence of a positive family history of these disorders. On the other hand, insulin resistance is associated with a proatherosclerotic disturbance in nitric oxide dependent vasodilation, probably contributing to the link between these two disorders. We examined the association between nitric oxide dependent vasodilation (measured with high resolution ultrasound at 13 MHz) and three relevant NO-synthase (eNOS)-polymorphisms in 200 insulin resistant subjects participating in the Tuebinger Lifestyle Intervention Program (TULIP). This study revealed that carriers of the eNOS intron 4 polymorphism (aa 2.16%; ab 24.2%; bb 73.2%) show significantly worse endothelial, and thereby eNOS dependent vasodilation (p=0.03, multivariate ANOVA), as compared to wildtype carriers. The 5' UTR T-786C and the G894 T polymorphism did not show any influence on eNOS-activity. In subjects at increased risk to develop type 2 diabetes, the eNOS intron 4 polymorphism is independently associated with endothelial function as indicated by disturbed endothelial NO production. Due to the high prevalence and the relatively strong effect, this polymorphism might help to identify subjects at increased risk for atherosclerosis associated with overweight and insulin resistance.

Testing alternative mechanisms of evolutionary divergence in an African rain forest passerine bird.

Abstract Models of speciation in African rain forests have stressed either the role of isolation or ecological gradients. Here we contrast patterns of morphological and genetic divergence in parapatric and allopatric populations of the Little Greenbul, Andropadus virens, within different and similar habitats. We sampled 263 individuals from 18 sites and four different habitat types in Upper and Lower Guinea. We show that despite relatively high rates of gene flow among populations, A. virens has undergone significant morphological divergence across the savanna-forest ecotone and mountain-forest boundaries. These data support a central component of the divergence-with-gene-flow model of speciation by suggesting that despite large amounts of gene flow, selection is sufficiently intense to cause morphological divergence. Despite evidence of isolation based on neutral genetic markers, we find little evidence of morphological divergence in fitness-related traits between hypothesized refugial areas. Although genetic evidence suggests populations in Upper and Lower Guinea have been isolated for over 2 million years, morphological divergence appears to be driven more by habitat differences than geographic isolation and suggests that selection in parapatry may be more important than geographic isolation in causing adaptive divergence in morphology.

A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone.

We conducted a prospective randomised study to compare the efficiency of out-patient progenitor cell mobilisation using either intermediate-dose cyclophosphamide (2 g/m(2)) and lenograstim at 5 micrograms/kg (Cyclo-G-CSF group, n=39) or lenograstim alone at 10 micrograms/kg (G-CSF group, n=40). The end points were to compare the impact of the two regimens on mobilisation efficiency, morbidity, time spent in hospital, the number of apheresis procedures required and engraftment kinetics. Successful mobilisation was achieved in 28/40 (70%) in the G-CSF group vs 22/39 (56.4%) for Cyclo-G-CSF (P=0.21). The median number of CD34+ cells mobilised was 2.3 x 10(6)/kg and 2.2 x 10(6)/kg for G-CSF and cyclo-G-CSF arms following a median of two apheresis procedures. Nausea and vomiting and total time spent in the hospital during mobilisation were significantly greater after Cyclo-G-CSF (P<0.05). Rapid neutrophil and platelet engraftment was achieved in all transplanted patients in both groups. In conclusion, G-CSF at 10 micrograms/kg was as efficient at mobilising progenitor cells as a combination of cyclophosphamide and G-CSF with reduced hospitalisation and side effects and prompt engraftment. When aggressive in-patient cytoreductive regimens are not required to both control disease and generate progenitor cells, the use of G-CSF alone appears preferable to combination with intermediate-dose cyclophosphamide.

Phylogeographical approaches to assessing demographic connectivity between breeding and overwintering regions in a Nearctic-Neotropical warbler (Wilsonia pusilla).

We characterized the pattern and magnitude of phylogeographical variation among breeding populations of a long-distance migratory bird, the Wilson's warbler (Wilsonia pusilla), and used this information to assess the utility of mtDNA markers for assaying demographic connectivity between breeding and overwintering regions. We found a complex pattern of population differentiation in mitochondrial DNA (mtDNA) variation among populations across the breeding range. Individuals from eastern North America were differentiated from western individuals and the eastern haplotypes formed a distinct, well-supported cluster. The more diverse western group contained haplotype clusters with significant geographical structuring, but there was also broad mixing of haplotype groups such that no haplotype groups were population specific and the predominance of rare haplotypes limited the utility of frequency-based assignment techniques. Nonetheless, the existence of geographically diagnosable eastern vs. western haplotypes enabled us to characterize the distribution of these two groups across 14 overwintering locations. Western haplotypes were present at much higher frequencies than eastern haplotypes at most overwintering sites. Application of this mtDNA-based method of linking breeding and overwintering populations on a finer geographical scale was precluded by the absence of population-specific markers and by insufficient haplotype sorting among western breeding populations. Our results suggest that because migratory species such as the Wilson's warbler likely experienced extensive gene flow among regional breeding populations, molecular markers will have the greatest utility for characterizing breeding-overwintering connectivity at a broad geographical scale.

Respiratory virus infections in adult T cell-depleted transplant recipients: the role of cellular immunity.

BACKGROUND: Little is known about the role of cellular immunity in respiratory virus infections after bone marrow transplantation. METHODS: Forty allograft recipients T-cell depleted with Campath antibodies were evaluated for respiratory virus infections in an active surveillance program with early initiation of antiviral therapy. RESULTS: Eighteen episodes of respiratory virus infection were detected in nine patients (22%) at a median of 95 days, with lower respiratory involvement in 44%. Fourteen episodes were treated with antiviral therapy for 7 to 46 days, with 11% mortality. Respiratory virus infections were more common in patients receiving Campath 100 mg in vivo, but delayed CD4+ recovery was the most significant risk factor. CONCLUSIONS: Respiratory virus infections are common and often recurrent in patients with severe CD4+ T lymphopenia. However, the mortality was low, which may have been due to early institution of antiviral treatment or reduced inflammatory damage to the lungs due to severe lymphopenia.

Profiles of adaptation in two similar viruses.

The related bacteriophages phiX174 and G4 were adapted to the inhibitory temperature of 44 degrees and monitored for nucleotide changes throughout the genome. Phage were evolved by serial transfer at low multiplicity of infection on rapidly dividing bacteria to select genotypes with the fastest rates of reproduction. Both phage showed overall greater fitness effects per substitution during the early stages of adaptation. The fitness of phiX174 improved from -0.7 to 5.6 doublings of phage concentration per generation. Five missense mutations were observed. The earliest two mutations accounted for 85% of the ultimate fitness gain. In contrast, G4 required adaptation to the intermediate temperature of 41.5 degrees before it could be maintained at 44 degrees. Its fitness at 44 degrees increased from -2.7 to 3.2, nearly the same net gain as in phiX174, but with three times the opportunity for adaptation. Seventeen mutations were observed in G4: 14 missense, 2 silent, and 1 intergenic. The first 3 missense substitutions accounted for over half the ultimate fitness increase. Although the expected pattern of periodic selective sweeps was the most common one for both phage, some mutations were lost after becoming frequent, and long-term polymorphism was observed. This study provides the greatest detail yet in combining fitness profiles with the underlying pattern of genetic changes, and the results support recent theories on the range of fitness effects of substitutions fixed during adaptation.

Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study.

Infections with the paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can result in serious morbidity and mortality after haemopoietic stem cell transplant (HSCT). Once pneumonia develops, the outcome of these infections is often poor despite anti-viral therapy. Aerosolised ribavirin has been evaluated as pre-emptive therapy for post-transplant RSV infections with some success. Due to the financial and logistic burden involved with the use of aerosolised ribavirin, we explored the efficacy and toxicity of oral ribavirin for pre-emptive therapy of post-transplant RSV and PIV infections in a dose escalating schedule (15-60 mg/kg/day). Five episodes each of RSV and PIV were treated in seven patients. Five patients were receiving treatment for GVHD and two acquired the infection in the pre-engraftment period. All the episodes of RSV infection improved with oral ribavirin with dose escalation to 30-45 mg/kg in three of them. On the other hand, only two of the five PIV infections improved with oral ribavirin. Of the three non-responders, two infections were acquired in the pre-engraftment period with one death from PIV pneumonia. Reversible anaemia was the only side-effect noted in patients treated for over 2 weeks. Thus, the use of oral ribavirin was well tolerated in the post-transplant period with no untoward toxicities. There was a trend towards better response in RSV infections, which needs to be further explored in controlled studies.

Refugial isolation versus ecological gradients. Testing alternative mechanisms of evolutionary divergence in four rainforest vertebrates.

Hypotheses for divergence and speciation in rainforests generally fall into two categories: those emphasizing the role of geographic isolation and those emphasizing the role of divergent selection along gradients. While a majority of studies have attempted to infer mechanisms based on the pattern of species richness and congruence of geographic boundaries, relatively few have tried to simultaneously test alternative hypotheses for diversification. Here we discuss four examples, taken from our work on diversification of tropical rainforest vertebrates, in which we examine patterns of genetic and morphological variation within and between biogeographic regions to address two alternative hypotheses. By estimating morphological divergence between geographically contiguous and isolated populations under similar and different ecological conditions, we attempt to evaluate the relative roles of geographic isolation and natural selection in population divergence. Results suggest that natural selection, even in the presence of appreciable gene flow, can result in morphological divergence that is greater than that found between populations isolated for millions of years and, in some cases, even greater than that found between congeneric, but distinct, species. The relatively small phenotypic divergence that occurs among long-term geographic isolates in similar habitats suggests that morphological divergence via drift may be negligible and/or that selection is acting to produce similar phenotypes in populations occupying similar habitats. Our results demonstrate that significant phenotypic divergence: (1) is not necessarily coupled with divergence in neutral molecular markers; and (2) can occur without geographic isolation in the presence of gene flow.

Parainfluenza virus type 3 infections in hematopoetic stem cell transplant recipients: response to ribavirin therapy.

Parainfluenza virus (PIV) infection can be a problem among hematopoetic stem cell transplant recipients. 125 patients were prospectively evaluated for respiratory viral infections. We describe 5 patients with PIV 3 infection and their response to early treatment with ribavirin.

Comparative avian phylogeography of Cameroon and equatorial Guinea mountains: implications for conservation.

We illustrate the use of Faith's 'Phylogenetic Diversity' measure to compare the phylogeographic structure of two bird species with patterns of avian endemism across six mountains in Cameroon and Equatorial Guinea. The Mountain Greenbul and Cameroon Blue-headed Sunbird showed phylogeographic patterns that together defined three biogeographic regions: Bioko, Mt. Cameroon, and the northern mountains of Cameroon. In contrast, the distributions of endemic species were largely a function of geographical distance, with close mountains sharing more endemic species than distant mountains. Moreover, for both species, populations on Mt. Cameroon were distinctive with respect to the ecologically relevant character bill size. Our results, while preliminary, illustrate the utility of a comparative approach for identifying geographical regions that harbour evolutionarily distinct populations and caution against using only the distributional patterns of endemics to prioritize regions for conservation. Results show that patterns of endemism may not be concordant with patterns of phylogenetic diversity nor morphological variation in a character important in fitness. While incorporation of additional species from unrelated taxa will be necessary to draw definitive conclusions about evolutionarily distinct regions, our preliminary results suggest a conservation approach for the Afromontane region of the Gulf of Guinea that would: (i) emphasize protection of both Bioko and Mt. Cameroon, thereby maximizing preservation of within-species phylogenetic and morphologic diversity; (ii) emphasize protection within the northern mountains to further conserve intraspecific phylogenetic diversity and maximize protection of endemic species.

Glacial vicariance and historical biogeography of rock ptarmigan (Lagopus mutus) in the Bering region.

In this paper, we address alternative hypotheses for the evolution of subspecies of rock ptarmigan (Lagopus mutus) endemic to the Aleutian Archipelago. To do this we examined patterns of genetic differentiation among populations of rock ptarmigan in the Aleutian Islands and parts of both Alaska and Siberia. Variation in mitochondrial control region sequences of 105 rock ptarmigan from 10 subspecies within the Bering region revealed three major phylogenetic lineages, two of which are endemic to the Aleutian Islands. Accordingly, haplotype and nucleotide diversities of rock ptarmigan within the archipelago are much higher than within mainland Alaska or Siberia. For Aleutian rock ptarmigan, analyses of molecular variance indicated significant genetic structuring and low estimates of gene flow among populations, despite small interisland distances within the archipelago. However, isolation by distance did not describe the pattern of gene flow or differentiation at this scale. Our estimates of divergence times of lineages suggest that Aleutian rock ptarmigan became isolated prior to the most recent Pleistocene glaciation event (late Wisconsin Stade) and that current patterns of genetic variation reflect the postglacial redistribution of divergent lineages and subsequent limited gene flow. In addition, genetic divergence among lineages was concordant with the distribution of plumage types among subspecies. The patterns of genetic variation described here for rock ptarmigan provide evidence for the role of glacial vicariance in contributing to genetic diversity within this and other Bering region species.

Role of Notch pathway in terminal follicle cell differentiation during Drosophila oogenesis.

During Drosophila oogenesis the body axes are determined by signaling between the oocyte and the somatic follicle cells that surround the egg chamber. A key event in the establishment of oocyte anterior-posterior polarity is the differential patterning of the follicle cell epithelium along the anterior-posterior axis. Both the Notch and epithelial growth factor (EGF) receptor pathways are required for this patterning. To understand how these pathways act in the process we have analyzed markers for anterior and posterior follicle cells accompanying constitutive activation of the EGF receptor, loss of Notch function, and ectopic expression of Delta. We find that a constitutively active EGF receptor can induce posterior fate in anterior but not in lateral follicle cells, showing that the EGF receptor pathway can act only on predetermined terminal cells. Furthermore, Notch function is required at both termini for appropriate expression of anterior and posterior markers, while loss of both the EGF receptor and Notch pathways mimic the Notch loss-of-function phenotype. Ectopic expression of the Notch ligand, Delta, disturbs EGF receptor dependent posterior follicle cell differentiation and anterior-posterior polarity of the oocyte. Our data are consistent with a model in which the Notch pathway is required for early follicle cell differentiation at both termini, but is then repressed at the posterior for proper determination of the posterior follicle cells by the EGF receptor pathway.