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Biomedical subjects

J Hassan

Publications and source records attributed to J Hassan.

At least 19 recordsLinked to original sources
PubMed2001

Human recent thymic emigrants--identification, expansion, and survival characteristics.

This study shows that, in humans at birth, circulating T cells represent recent thymic emigrants (RTEs) as reflected in their high level of expression of TCR excision circles. RTEs express "thymocyte-like" characteristics with regard to rapid rate of apoptosis. In the presence of common gamma-chain cytokines, in particular IL-7, they show enhanced potential to survive, entry into cell cycle, and proliferation. Although common gamma-chain cytokines were also potent antiapoptotic stimuli for mature adult-derived naive CD4+CD45RA+ T cells, these cells were refractory to IL-7-induced expansion in vitro. RTEs cultured with IL-7 could not reinduce recombination-activating gene-2 gene expression in vitro. These data suggest that postthymic naive T cells in the periphery during early life are at a unique stage in ontogeny as RTEs, during which they can undergo homeostatic regulation including expansion and survival in an Ag-independent manner while maintaining their preselected TCR repertoire.

Adult↗
PubMed2000

Behavioral characterization and genetic analysis of the Drosophila melanogaster larval response to light as revealed by a novel individual assay.

A new assay was designed, named checker, that measures the individual response to light in the fruitfly Drosophila melanogaster larva. In this assay the Drosophila larva apparently modulates its pattern of locomotion when faced with a choice between a dark and lit environment by orienting its movement towards the dark environment. We show that, in this assay, a response to light can be measured as an increase in residence time in the dark versus the lit quadrant. Mutations that disrupt phototransduction in the adult Drosophila abolish the larval response to light, demonstrating that this larval visual function is similar to that of the adult fly. Similarly, no response to light was detected in strains where the larval visual system (photoreceptors and target area) was disrupted by a mutation in the homeobox containing gene sine oculis (so) gene. Ablation of photoreceptors by the targeted expression of the cell death gene hid under the control of the photoreceptor-specific transcription factor glass (gl) abolishes this response entirely. Finally, we demonstrate that this response to light can be mediated by rhodopsins other than the blue absorbing Rh1.

Animals↗
PubMed1998

IL-7 promotes the survival and maturation but not differentiation of human post-thymic CD4+ T cells.

This study examines the influence of IL-7 on post-thymic CD4+ T cells using cord blood as a model system. Survival of naive cord blood T cells in the presence of IL-7 alone was significantly prolonged by up-regulating bcl-2, thereby preventing apoptosis while maintaining maximal cell viability. Cultures without IL-7 showed high rates of apoptosis resulting in 50% cell death by day 5 of culture. Upon phorbol 12-myristate 13-acetate + ionomycin stimulation, accumulation of cytoplasmic IL-2 was similar to that observed in freshly isolated cells, but no IL-4- or IFN-gamma-positive cells were detected. IL-7 maintained the naive T cells in a quiescent state expressing the CD45RA antigen. A significant finding was the loss of CD38 antigen expression on the naive cord blood T cells to levels similar to that observed on adult naive T cells. In contrast to the reduced proliferative response of fresh cord blood T cells to anti-CD2 + CD28 stimulation, the proliferative response of IL-7-treated cells was similar to that of adult naive T cells. This study shows that as well as maintaining the naive T cell pool by enhancing cell survival and up-regulating bcl-2 expression, IL-7 also functions as a maturation factor for post-thymic naive T cells.

ADP-ribosyl Cyclase↗
PubMed1997

Linkage of protein kinase C-beta activation and intracellular interleukin-2 accumulation in human naive CD4 T cells.

A critical role for protein kinase C (PKC) in signal transduction events has been well established. Moreover, studies of regulation in PKC levels suggest participation in mediating long-term cellular functions. Protein kinase C-beta (PKC-beta) has been reported to be involved in interleukin-2 (IL-2) synthesis in T lymphocytes. In this study, the role of PKC-beta in intracellular accumulation of IL-2 was investigated using specific inhibitors. Preincubation with two different PKC inhibitors, one specific for classical isotypes (alpha and beta I) Go6976, and one which inhibits both classical and non-classical isotypes, GF109203X, caused a complete block in cytoplasmic IL-2 accumulation when naive CD4 T cells were stimulated in the presence of CD2+CD28+phorbol myristate acetate (PMA). In contrast, preincubation with up to 1000 ng/ml of cyclosporin A (CsA) resulted in a reduction in the intracellular IL-2 detected, as observed by a decrease in the proportion of positive cells as well as a fall in the mean fluorescence intensity (MFI). CsA did not influence PKC-beta translocation. Flow cytometric assessments of PKC-beta and its isoforms beta I and beta II correlated with Western blotting analysis and these results were further supported by the use of PKC-beta-positive (HUT 78) and -negative (BW5147) T-cell lines. Using the specific inhibitors, Go6976 and GF109203X, the findings in this study suggest that activation and translocation of PKC-beta is critical for accumulation of intracellular IL-2. The influence of CsA in reducing but not blocking IL-2 synthesis is discussed. PMA-induced down-regulation of the CD4 antigen was observed in the presence of Go6976 and but not GF109203X, suggesting regulation by non-classical PKC isoforms.

Blotting, Western↗
PubMed1997

Cord blood CD4+ CD45RA+ T cells achieve a lower magnitude of activation when compared with their adult counterparts.

Highly purified CD4+ CD45RA+ cells from cord blood and peripheral blood from healthy adults were studied. The levels of expression of the CD2, CD3, CD4 and CD28 antigens were similar; however, CD45 and CD45RA antigen expression were slightly lower in cord cells. The reduced expression of the CD45RA antigen on cord CD4+ T cells was confirmed in whole blood. Functional assessment revealed deficiencies in cord CD4+ CD45RA+ T cells. Interleukin-2 (IL-2) production in response to specific triggering via CD2 monoclonal antibody (mAb) alone, or CD2 mAb in combination with CD28 mAb showed marked underproduction (about 10% of adult production). When CD25 expression was examined, it was observed that the proportion of activated CD4+ CD45RA+ T cells in cord blood was lower than in adult (about 20% of adult expression). Proliferation to CD2 mAbs or CD2 + 28 mAbs of cord blood native cells was similarly depressed. Investigation of IL-2 mRNA expression under these stimulatory conditions paralleled the results observed for CD25 expression, IL-2 production and proliferation. When phorbol 12-myristate 13-acetate (PMA) was added to the cells triggered with CD2 + 28mAbs, the responses examined were enhanced in both cord and adult blood with no significant differences between the groups. These findings suggest that under identical conditions of stimulation, purified cord blood CD4+ CD45RA+ T cells do not acquire similar activation status as their adult counterparts. These findings may help in understanding the reduced graft-versus-host disease (GVHD) observed in cord blood stem cell transplantation.

Adult↗
PubMed1997

Abdominal circumference in fetuses with congenital diaphragmatic hernia: correlation with hernia content and pregnancy outcome.

To assess the value of abdominal circumference measurements in the second trimester as a predictor of mortality in fetuses with congenital diaphragmatic hernia, 34 fetuses with this condition who had had second trimester ultrasonographic evaluation were analyzed retrospectively for abdominal circumference measurements, content of the hernia, and pregnancy outcome. The abdominal circumference was below the fifth percentile in nine of the 27 fetuses (33%) with an isolated defect and in five of the seven fetuses (71%) with additional anomalies. In fetuses with isolated congenital diaphragmatic hernia, an abdominal circumference measurement below the fifth percentile was associated with the presence of the liver (P < 0.05) but not of the stomach in the chest. In 19 continuing pregnancies with an isolated defect, all five fetuses with an abdominal circumference below the fifth percentile either died prenatally (n = 1), soon after birth (n = 1), or after surgery (n = 3). In contrast, only six of the 14 fetuses (43%) with an abdominal circumference measurement within the normal range died, either soon after birth (n = 2) or after surgery (n = 4) (P < 0.05). We conclude that an abdominal circumference measurement below the fifth percentile in the second trimester appears to be a good predictor of a poor prognosis in fetuses with congenital diaphragmatic hernia.

Abdomen↗
PubMed1997

Prenatal diagnosis of diastematomyelia: case reports and review of the literature.

Diastematomyelia is a rare malformation characterized by complete or incomplete division of the spinal cord by osseous or fibrocartilaginous septum. Most cases are seen in association with other anomalies of the vertebral column such as spina bifida, kyphoscoliosis, butterfly vertebra, and hemivertebra. In this report we describe two cases of isolated diastematomyelia detected at routine second-trimester detailed ultrasound scan, the most striking feature being the detection of an echogenic focus in the posterior aspect of the spine in association with widening of the interpedicular vertebral space. The prenatal literature is reviewed to assess the clinical significance of this finding.

Adult↗
PubMed1997

Prenatal sonographic diagnosis of cleidocranial dysostosis.

Cleidocranial dysostosis is an autosomal dominant disorder characterized by absence or hypoplasia of the clavicles, skull abnormalities, and abnormal dentition. The prenatal diagnosis of this condition has been reported once previously in a known high-risk pregnancy. In this report we describe the prenatal findings of cleidocranial dysostosis at 19 weeks' gestation in a woman affected with this disorder but undiagnosed before the fetal scan. This report is unique in the sense that an autosomal dominant condition diagnosed in the fetus led to a similar diagnosis in the mother.

Adult↗
PubMed1996

Glioependymal and arachnoid cysts: unusual causes of early ventriculomegaly in utero.

In this report we describe two cases of fetal midline intracranial cyst presenting with ventriculomegaly at routine detailed second-trimester scan. In the first case, additional findings included a banana-shaped hypoplastic cerebellum and macrocephaly; autopsy after termination of the pregnancy revealed a glioependymal cyst. In the second case, subsequent follow-up examination revealed a progressive increase in cyst size and worsening of ventriculomegaly; termination of pregnancy was performed at 24 weeks and autopsy confirmed an arachnoid cyst. These cases document interhemispheric cyst as a cause for early ventriculomegaly in utero.

Adult↗
PubMed1996

Reduced primary antigen-specific T-cell precursor frequencies in neonates is associated with deficient interleukin-2 production.

Clinical evidence has indicated that the neonatal cell-mediated immune response to primary infection is delayed when compared to that of adults with the same primary infection. The mechanisms regulating the development of antigen-specific T-cell immunity in neonates remain to be elucidated. We examined the primary immune response to the non-recall antigen, keyhole limpet haemocyanin (KLH) in adults and neonates in vitro. We report here that conventional bulk culture methods show reduced proliferative responses in neonates although statistical significance was not achieved. Using limiting dilution analysis, the frequencies of KLH-specific T lymphocytes were 10-100-fold lower in neonates when compared to adults. Interleukin-2 (IL-2) production was significantly lower in the supernatants of neonatal mononuclear cells (MNC) stimulated with KLH when compared to adults. Addition of exogenous IL-2 increased precursor frequencies twofold in both adult and newborn cultures. In contrast to the secreted IL-2 levels, IL-2 mRNA expression was higher in antigen-stimulated neonatal MNC preparations, even though proliferation was lower. These observations indicate differential in vitro responsiveness in neonates and adults to primary antigenic challenge. Since no IL-2 was detected in cell lysates, the presence of high levels of IL-2 mRNA and low IL-2 production suggests inability by neonatal MNC to translate IL-2. This deficiency in IL-2 production may explain the reduced precursor frequencies, suggesting failure to recruit T lymphocytes in order to expand the KLH-specific T-cell response. These observations are important for the understanding of the development of primary immune responses and immunological maturation in neonates.

Adult↗
PubMed1996

Is isolated second-trimester hyperechogenic bowel a predictor of suboptimal fetal growth?

Hyperechogenic bowel has been described as a normal variant in second-trimester fetuses, but also in association with cystic fibrosis, chromosomal abnormalities, congenital infection, intestinal obstruction and intra-amniotic bleeding. These fetuses are also at risk for poor perinatal outcome, mainly due to intrauterine growth retardation. In this report we examine the potential of ultrasonographic detection of isolated fetal hyperechogenic bowel in the second trimester as a marker of subsequent suboptimal fetal growth. Second-trimester fetuses with hyperechogenic bowel in comparison to controls had a greater incidence of birth weight below the 10th centile (6/48, 12.5% vs. 4/149, 2.7%, respectively; p = 0.01) and lower mean birth weight (3176 g (SD 741 vs. 3499 g (SD 493)), respectively; p = 0.001). There was no difference in the prevalence of preterm delivery in both groups (3/48, 6.3% vs. 8/149, 5.4%, respectively; p = 0.7). This study suggests that second-trimester fetuses normally-grown with isolated hyperechogenic bowel are at risk for suboptimal fetal growth.

Female↗
PubMed1996

Umbilical vein to artery ratio in fetuses with single umbilical artery.

In fetuses with single umbilical artery (SUA) the entire blood flow to the placenta is transported through only one umbilical artery, resulting in a compensatory increase of the arterial diameter. In order to establish whether umbilical vessel size could be used as an additional ultrasonographic criterion for prenatal diagnosis of SUA, we measured umbilical vein and umbilical artery diameters in 55 fetuses with SUA and in 55 with a normal three-vessel cord matched for gestational age. In all but one fetus with SUA, the diameter of the umbilical artery was greater than 50% of that of the umbilical vein, resulting in an umbilical vein to umbilical artery ratio of < or = 2. In contrast, none of the fetuses with a three-vessel cord had a ratio of < or = 2. Increasing diameter of the umbilical artery with no modification of the diameter of the vein is a characteristic prenatal ultrasonographic feature of SUA, making this observation a useful technique for the detection of this vascular anomaly in utero.

Female↗
PubMed1996

Increased numbers of CD5+ B cells and T cell receptor (TCR) gamma delta+ T cells are associated with younger age of onset in rheumatoid arthritis (RA).

Patients presenting with RA before the age of 45 years (younger onset) are known to have more aggressive disease compared with patients presenting after the age of 65 years (older onset). Coordinated expansion of circulating CD5+ B cell and TCR gamma delta+ T cell levels has been reported in patients with RA. This study assesses the peripheral blood levels of these two cell types in RA patients with younger and older onset of disease. CD5+ B cell levels were significantly elevated in the younger onset RA group (26.6+/-4.5%) compared with the older onset RA group (14.2+/-1.2%; P<0.01). TCR gamma delta+ T cell levels were also significantly raised in the young patients (4.0+/-0.9%) compared with elderly patients (1.6+/-0.2%; P<0.01). T cell levels (CD3+) were similar in both groups (young 66.4+/-3.3%; old 74.3+/-3.4% (mean+/-s.e.m.); NS). Total B cell levels (CD19+) were also similar in these groups (7.7+/-0.7% versus 8.9+/-1.8%; NS). A significant positive correlation was observed between the CD5+ B and TCR gamma delta+ T cell types in the patients (r=0.72, P<0.05). Compared with age-matched normal controls, the younger onset patients had similar CD5+ B cell and TCR gamma delta+ T cell levels to the elderly controls (CD5+ B cells 30.2+/-3.0%; TCR gamma delta+ T cells 3.0+/-0.8%). Conversely, older onset RA patients had CD5+ B cell levels similar to the young controls (12.3+/-1.9%). Spontaneous in vitro synthesis of immunoglobulins (IgM, IgA and IgG) and rheumatoid factors (IgM and IgA isotypes) were not significantly different in both patient groups. The coordinate expansion of circulating CD5+ B cells and gamma delta+ T cells seen in patients with RA presenting before 45 years of age and not after 65 years of age may suggest a potential role for these cells in more aggressive disease states.

Adult↗
PubMed1995

Ablation of acardiac twin by alcohol injection into the intra-abdominal umbilical artery.

BACKGROUND: Twin reversed arterial perfusion sequence is a rare complication of monochorionic twinning, in which the normal pump twin perfuses the abnormal acardiac twin in a reversed fashion via an artery-to-artery placental anastomosis. Mortality in the normal twin exceeds 50% as a result of preterm labor, polyhydramnios, and congestive heart failure. CASE: A twin pregnancy complicated by the twin reversed arterial perfusion sequence developed early hemodynamic decompensation in the pump twin with increasing size of the acardiac twin. Ablation of the acardiac twin at 23 weeks' gestation was achieved successfully by injecting 1 mL of absolute alcohol into the intra-abdominal portion of the single umbilical artery. CONCLUSION: Direct ultrasound-guided intravascular injection of absolute alcohol is an easy and straightforward technique to occlude circulation to the acardiac twin. This vessel can be identified easily by color Doppler ultrasonography away from the main venous trunk. Selection of this target, rather than occlusion at the level of the umbilical cord, could reduce the risks of cord accidents and inadvertent intravenous injection of the ablative material.

Abdomen↗