Biomedical subjects

H Raphael

Publications and source records attributed to H Raphael.

8 recordsLinked to original sources

PubMed2001

EGFRs mediate chemotactic migration in the developing telencephalon.

Epidermal growth factor receptors (EGFRs) have been implicated in the control of migration in the telencephalon, but the mechanism underlying their contribution is unclear. We show that expression of a threshold level of EGFRs confers chemotactic competence in stem cells, neurons and astrocytes in cortical explants. This level of receptor expression is normally achieved by a subpopulation of cells during mid-embryonic development. Cells that express high levels of EGFR are located in migration pathways, including the tangential pathway to the olfactory bulb via the rostral migratory stream (RMS), the lateral cortical stream (LCS) leading to ventrolateral cortex and the radial pathway from proliferative zones to cortical plate. The targets of these pathways express the ligands HB-EGF and/or TGFalpha. To test the idea that EGFRs mediate chemotactic migration these pathways, we increased the size of the population of cells expressing threshold levels of EGFRs in vivo by viral transduction. Our results suggest that EGFRs mediate migration radially to the cortical plate and ventrolaterally in the LCS, but not tangentially in the RMS. Within the bulb, however, EGFRs also mediate radial migration. Our findings suggest that developmental changes in EGFR expression, together with changes in ligand expression regulate the migration of specific populations of cells in the telencephalon by a chemoattractive mechanism.

Animals↗

PubMed2000

BMP and FGF regulate the development of EGF-responsive neural progenitor cells.

Temporal changes in progenitor cell responses to extrinsic signals play an important role in development, but little is known about the mechanisms that determine how these changes occur. In the rodent CNS, expression of epidermal growth factor receptors (EGFRs) increases during embryonic development, conferring mitotic responsiveness to EGF among multipotent stem cells. Here we show that cell-cell signaling controls this change. Whereas EGF-responsive stem cells develop on schedule in explant and aggregate cultures of embryonic cortex, co-culture with younger cortical cells delays their development. Exogenous BMP4 mimics the effect of younger cells, reversibly inhibiting changes in EGFR expression and responsiveness. Moreover, blocking endogenous BMP receptors in progenitors with a virus transducing dnBMPR1B accelerates changes in EGFR signaling. This involves a non-cell-autonomous mechanism, suggesting that BMP negatively regulates signal(s) that promote the development of EGF-responsive stem cells. FGF2 is a good candidate for such a signal, as we find that it antagonizes the inhibitory effects of younger cortical cells and exogenous BMP4. These findings suggest that a balance between antagonistic extrinsic signals regulates temporal changes in an intrinsic property of neural progenitor cells.

Animals↗

PubMed1999

Prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in general practice setting: cross sectional survey.

OBJECTIVE: To assess the prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in the general practice setting by echocardiographic assessment of ventricular function. DESIGN: Cross sectional survey. SETTING: Four centre general practice in Poole, Dorset. SUBJECTS: 817 elderly patients aged 70-84 years. MAIN OUTCOMES: Echocardiographic assessment of left ventricular systolic function including measurement of ejection fraction by biplane summation method where possible, clinical symptoms, and signs of left ventricular dysfunction. RESULTS: The overall prevalence of left ventricular systolic dysfunction was 7.5% (95% confidence interval 5.8% to 9.5%); mild dysfunction (5.0%) was considerably more prevalent than moderate (1.6%) or severe dysfunction (0.7%). Measurement of ejection fraction was possible in 82% of patients (n=667): in patients categorised as having mild, moderate, or severe dysfunction, the mean ejection fraction was 48% (SD 12.0), 38% (8.1), and 26% (7.9) respectively. At all ages the prevalence was much higher in men than in women (odds ratio 5.1, 95% confidence interval 2.6 to 10.1). No clinical symptom or sign was both sensitive and specific. In around half the patients with ventricular dysfunction (52%, 32/61) heart failure had not been previously diagnosed. CONCLUSIONS: Unrecognised left ventricular dysfunction is a common problem in elderly patients in the general practice setting. Appropriate treatment with angiotensin converting enzyme inhibitors has the potential to reduce hospitalisation and mortality in these patients, but diagnosis should not be based on clinical history and examination alone. Screening is feasible in general practice, but it should not be implemented until the optimum method of identifying left ventricular dysfunction is clarified, and the cost effectiveness of screening has been shown.

Aged↗

PubMed1987

A comparative study of T-cell depleted and non-depleted marrow transplantation for hematological malignancy.

Sixteen patients with hematological malignancy received cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 Gy), oral cyclosporin, and an HLA-identical sibling marrow transplant depleted of T cells by incubation with the monoclonal antibody anti-HuLy-m1 (CD2) and rabbit complement with (five patients) or without (11 patients) anti-HuLy-m8). These 16 patients were compared historically to 84 patients with hematological malignancy receiving cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 or 14 Gy), oral cyclosporin, and unmanipulated HLA-identical sibling marrow, for parameters of engraftment and graft-versus-host disease (GVHD). Graft failure occurred in one of the 16 T-cell depleted recipients and in one of the 84 nondepleted recipients. Engraftment was slightly but significantly slower in the T-cell depleted group and bacterial infections significantly more frequent and severe than in the unmanipulated group. There was a suggestion that the severity of acute GVHD was reduced in those receiving T depleted marrow. Randomized trials will be necessary to determine if marrow T-cell depletion results in superior long-term leukemia-free survival.

Acute Disease↗

PubMed1986

The impact of leukemia status at the time of HLA-identical sibling marrow transplantation on subsequent complication rate and survival of adults with acute leukemia.

Between March 1981 and March 1985, 76 patients with acute leukemia were treated with cyclophosphamide (120 mg/kg), 12 or 14 Gy total body irradiation, and an HLA-identical sibling marrow transplant. Forty-seven patients had acute non-lymphoblastic leukemia (ANLL) and 29 had acute lymphoblastic leukemia (ALL). Forty-one were transplanted during first remission and 28 during or after first relapse of their disease. An additional six patients were transplanted because their leukemia was refractory to conventional cytotoxic chemotherapy, and one was transplanted as initial therapy. Actuarial 42 month survival for those transplanted during first remission was 47% and for those transplanted in first relapse or later it was 22% (p = 0.02). There was no difference in either group between those with ANLL and those with ALL. Two of the six patients with refractory leukemia are alive more than 22 and more than 15 months after the transplant. The incidence of acute graft-versus-host disease and interstitial pneumonitis was 90% and 39%, respectively, for the first remission group, and 96% and 37% for those transplanted in first relapse or later. There was no significant difference in transplant-related mortality between the two groups (29% and 43%, respectively). The leukemia recurrence rate, however, was 13% for those transplanted in first remission and 67% for those transplanted in first relapse or later (p = 0.0003). Thus, the major factor determining the incidence of leukemia recurrence and survival after transplant was the status of the leukemia at the time of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

PubMed1986

Aplastic anemia: analysis of two methods of treatment.

Between 1981 and 1985, 27 patients with aplastic anemia have been treated by immunosuppression with antilymphocyte globulin and prednisolone or allogeneic bone marrow transplantation. Fifteen have undergone bone marrow transplantation and have an actuarial survival at 54 months of 65% +/- 12% (95% confidence limits). There have been four deaths from graft rejection, septicemia (two), and graft-versus-host disease. Twelve have received antilymphocyte globulin and have an actuarial survival at 56 months of 67% +/- 21%. Five of these now have a normal blood count and two have had good partial responses and are self supporting. Of the five non-responders, three survived, two with persistent aplasia and one after allogeneic bone marrow transplantation. Two are dead, one of hemorrhage and one after mismatched bone marrow transplantation. In this study antilymphocyte globulin produced survival equivalent to bone marrow transplantation although only 58% of patients had a response to the antilymphocyte globulin. The advantages and disadvantages of these two methods of treatment are discussed.

Adolescent↗

PubMedDate not supplied

Family views of a paediatric outpatient nursing development unit.

This article reports on one aspect of the quinquennial evaluation of a King's Fund accredited nursing development unit (NDU) within a paediatric outpatient department of a large district general hospital during the period 1993-1998. The study draws upon descriptive data obtained through a parental satisfaction survey. Overall the results demonstrate a high degree of satisfaction with the outpatient visit family experience and suggest that the status of NDU has helped the children's outpatient department become more responsive to the needs of families.

Attitude to Health↗

PubMedDate not supplied

Multiprofessional perceptions of a paediatric nursing development unit.

This article describes the final component of the quinquennial evaluation of a King's Fund accredited nursing development unit (NDU) within a paediatric outpatient department of a large district general hospital during the period 1993-1998. The study draws upon descriptive data obtained through a questionnaire distributed to 83 members of staff associated with the outpatient department. Overall, the results demonstrate that NDU status has enabled staff to embrace the change process more readily than might have been possible otherwise. The basic premise that NDUs should promote nursing innovation is explored and critically evaluated.

Attitude of Health Personnel↗