Biomedical subjects

E Chen

Publications and source records attributed to E Chen.

At least 127 records · Page 7Linked to original sources

PubMed1996

Chromosome 22q11.2 microdeletions in velocardiofacial syndrome patients with widely variable manifestations.

Velocardiofacial syndrome (VCFS) and the DiGeorge sequence (DGS) are caused by 22q11.2 deletions. Fluorescence in situ hybridization (FISH) using the DiGeorge chromosome region (DGCR) probe (Oncor) was used to detect 31 deletions in 100 patients with possible VCFS. Retrospective FISH analysis of archived slides from 14 patients originally studied only by high-resolution G banding detected 6 patients with a DGCR deletion, and only 2 of these 6 had a microscopically visible chromosome deletion. The 4 familial deletions found exhibited a wide range of clinical presentations within each family. Comparison of clinical characteristics of patients with and without the DGCR deletion determined findings predictive of the deletion: abundant or unruly scalp hair; narrow palpebral fissures; a laterally "built-up" nose; velopharyngeal inadequacy; thymic hypoplasia; and congenital heart defects, specifically tetralogy of Fallot, ventriculoseptal defect, and interrupted aortic arch.

Adolescent↗

PubMed1996

Distichiasis-lymphedema syndrome: tetralogy of Fallot, chylothorax, and neonatal death.

We describe a newborn female with a severe presentation of distichiasis-lymphedema syndrome (McKusick 15340). She was initially evaluated because of a phenotype suggestive of Ullrich-Turner or Noonan syndrome (low posterior hairline, cupped ears, severe pterygium colli, heart murmur, and pectus excavatum). Distichiasis was noted at age 6 weeks. Subsequent to surgery for tetralogy of Fallot, patent ductus arteriosus, and branch pulmonic stenosis, she developed persistent chylothorax and sepsis. She died at 3 months. Family history indicated segregation of distichiasis-lymphedema syndrome. She was the sixth member in her family to have this disorder and was the most severely affected.

Abnormalities, Multiple↗

PubMed1996

Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth disorder recently shown to be caused by mutations in the heparan sulfate proteoglycan GPC3 [Pilia et al., Nat Genet; 12:241-247 1996]. We have used Southern blot analysis and polymerase chain reaction amplification of intra-exonic sequences to identify four new GPC3 mutations and further characterize three previously reported SGBS mutations. De novo GPC3 mutations were identified in 2 families. In general, the mutations were unique deletions ranging from less than 0.1 kb to more than 300 kb in length with no evidence of a mutational hot spot discerned. The lack of correlation between the phenotype of 18 affected males from these 7 families and the location and size of the GPC3 gene mutations suggest that SGBS is caused by a nonfunctional GPC3 protein.

Abnormalities, Multiple↗

PubMed1996

Ordered shotgun sequencing of a 135 kb Xq25 YAC containing ANT2 and four possible genes, including three confirmed by EST matches.

Ordered shotgun sequencing (OSS) has been successfully carried out with an Xq25 YAC substrate. yWXD703 DNA was subcloned into lambda phage and sequences of insert ends of the lambda subclones were used to generate a map to select a minimum tiling path of clones to be completely sequenced. The sequence of 135 038 nt contains the entire ANT2 cDNA as well as four other candidates suggested by computer-assisted analyses. One of the putative genes is homologous to a gene implicated in Graves' disease and it, ANT2 and two others are confirmed by EST matches. The results suggest that OSS can be applied to YACs in accord with earlier simulations and further indicate that the sequence of the YAC accurately reflects the sequence of uncloned human DNA.

Bacteriophage lambda↗

PubMed1996

Genetic characterization of a mammalian protein-protein interaction domain by using a yeast reverse two-hybrid system.

Many biological processes rely upon protein-protein interactions. Hence, detailed analysis of these interactions is critical for their understanding. Due to the complexities involved, genetic approaches are often needed. In yeast and phage, genetic characterizations of protein complexes are possible. However, in multicellular organisms, such characterizations are limited by the lack of powerful selection systems. Herein we describe genetic selections that allow single amino acid changes that disrupt protein-protein interactions to be selected from large libraries of randomly generated mutant alleles. The strategy, based on a yeast reverse two-hybrid system, involves a first-step negative selection for mutations that affect interaction, followed by a second-step positive selection for a subset of these mutations that maintain expression of full-length protein (two-step selection). We have selected such mutations in the transcription factor E2F1 that affect its ability to heterodimerize with DP1. The mutations obtained identified a putative helix in the marked box, a region conserved among E2F family members, as an important determinant for interaction. This two-step selection procedure can be used to characterize any interaction domain that can be tested in the two-hybrid system.

Alleles↗

PubMed1996

A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma.

BACKGROUND: Patients who have had major trauma are at very high risk for venous thromboembolism if they do not receive thromboprophylaxis. We compared low-dose heparin and a low-molecular-weight heparin with regard to efficacy and safety in a randomized clinical trial in patients with trauma. METHODS: Consecutive adult patients admitted to a trauma center who had Injury Severity Scores of at least 9 and no intracranial bleeding were randomly assigned to heparin (5000 units) or enoxaprin (30 mg), each given subcutaneously every 12 hours in a double-blind manner, beginning within 36 hours after the injury. The primary outcome was deep-vein thrombosis as assessed by contrast venography performed on or before day 14 after randomization. RESULTS: Among 344 randomized patients, 136 who received low-dose heparin and 129 who received enoxaparin had venograms adequate for analysis. Sixty patients given heparin (44 percent) and 40 patients given enoxaparin (31 percent) had deep-vein thrombosis (P=0.014). The rates of proximal-vein thrombosis were 15 percent and 6 percent, respectively (P=0.012). The reductions in risk with enoxaparin as compared with heparin were 30 percent (95 percent confidence interval, 4 to 50 percent) for all deep-vein thrombosis and 58 percent (95 percent confidence interval, 12 to 87 percent) for proximal-vein thrombosis. Only six patients (1.7 percent) had major bleeding (one in the heparin group and five in the enoxaparin group, P=0.12). CONCLUSIONS: Low-molecular-weight heparin was more effective than low-dose heparin in preventing venous thromboembolism after major trauma. Both interventions were safe.

Adult↗

PubMed1996

Cesarean delivery in relation to birth weight and gestational glucose tolerance: pathophysiology or practice style? Toronto Trihospital Gestational Diabetes Investigators.

OBJECTIVES: To examine the relationship between birth weight and mode of delivery among women with untreated borderline gestational diabetes mellitus (GDM), treated overt GDM, and normoglycemia. DESIGN: Prospective cohort study. SETTING: Three Toronto, Ontario teaching hospitals. PATIENTS: A total of 3778 volunteers aged 24 years or older. INTERVENTIONS: Subjects underwent a 3-hour long, 100-g oral glucose tolerance test at 28 weeks' gestation, regardless of screening test results. Usual care was provided to 143 women who met the National Diabetes Data Group criteria for GDM. Physicians were blinded to glucose tolerance test results for all others, including 115 untreated women with borderline GDM by the broader criteria of Carpenter and Coustan. MAIN OUTCOME MEASURES: Crude and adjusted rates of cesarean delivery and neonatal macrosomia (birth weight >4000 g). RESULTS: Compared with normoglycemic controls, the untreated borderline GDM group had increased rates of macrosomia (28.7% vs 13.7%, P<.001) and cesarean delivery (29.6% vs 20.2%, P=.02). Cesarean delivery in this subgroup was associated with macrosomia (45.5% vs 23.5%, P=.03). Usual care of known GDM normalized birth weights, but the cesarean delivery rate was about 33% whether macrosomia was present or absent. A clearly increased risk of cesarean delivery among treated patients compared with normoglycemic controls persisted after adjustment for multiple maternal risk factors (adjusted odds ratio, 2.1; 95% confidence interval, 1.3 to 3.6). CONCLUSIONS: Infant macrosomia was a mediating factor in high cesarean delivery rates for women with untreated borderline GDM. While detection and treatment of GDM normalized birth weights, rates of cesarean delivery remained inexplicably high. Recognition of GDM may lead to a lower threshold for surgical delivery that mitigates the potential benefits of treatment.

Adult↗

PubMed1996

Cleavage of oligoribonucleotides by the 2',5'-oligoadenylate- dependent ribonuclease L.

RNase L, the 2',5' oligoadenylate-dependent ribonuclease, is one of the enzyme systems important in the cellular response to interferon. When activated in the presence of 2',5'-linked oligoadenylates, RNase L can catalyze the cleavage of synthetic oligoribonucleotides that contain dyad sequences of the forms UU, UA, AU, AA, and UG, but it cannot catalyze the cleavage of an oligoribonucleotide containing only cytosines. The primary site of the cleavage reaction with the substrate C11UUC7 has been defined to be 3' of the UU dyad by labeling either the 5' or the 3' end of the oligoribonucleotide and by examining the reaction products on polyacrylamide sequencing gels. Reaction time courses have been used to determine the kinetic parameters of the cleavage reactions. The effect of the overall length of the oligomeric substrate as well as the sequence of the bases around the position of the cleavage site on the kinetics of the cleavage reaction has been examined. The efficiency with which activated RNase L catalyzes the cleavage of the substrate C11UUC7 is 1.9 x 10(7) m-1 s-1. Because the cleavage of the synthetic oligoribonucleotide can be used to monitor the steady-state kinetics of catalysis by activated RNase L, this method offers an advantage over previous methods of assay for RNase L activity.

Adenine Nucleotides↗

PubMed1996

Mechanism of native oat phytochrome photoreversion: a time-resolved absorption investigation.

The regulation of plant photomorphogenesis is mediated by the thermal reactions that follow light absorption by the phytochrome photoreceptor. Phytochromes are tetrapyrrolic chromoproteins that exist in two photochromically interconvertible forms, a red light absorbing species, Pr, and a far-red light absorbing form, Pfr. Upon irradiation with 670 nm light, the inactive, red light sensing Pr form is converted to the active Pfr form. Although the forward phototransformation has been studied extensively by several groups using various techniques, the Pfr-->Pr photoreversion reaction that occurs upon irradiation with 730 nm light is not as thoroughly characterized. In this study, time-resolved absorption (TROD) spectroscopy is used to examine the intermediate species involved in the phytochrome photoreversion mechanism at 10 degrees C. Analysis of the TROD data identifies three species with lifetimes of 320 ns, 265 microseconds, and 5.5 ms. TROD results are described in terms of the simplest parallel and sequential kinetic models. Comparison of intermediate spectra from these mechanisms with those of previously reported species from flash photoreversion and low-temperature studies indicates that Pfr photoreversion follows a sequential pathway that does not share any intermediates with the Pr phototransformation pathway.

Avena↗

PubMed1996

CT of submandibular gland sialolithiasis.

We emphasise the importance of high-resolution CT with reconstruction in the demonstration of submandibular gland (SMG) sialolithiasis and its role in monitoring treatment. We studied 76 patients with swollen and tender SMG, some with fever. They underwent conventional radiography, sonography (US) and high-resolution CT with reconstructions. Conventional radiographs demonstrated single stones in 29 patients. Axial CT, before reconstructions, demonstrated single stones in 63 patients and multiple stones in another 5. Following CT reconstructions, multiple stones were demonstrated in 37 patients. On US stones were diagnosed in only 33 patients, and multiple stones in only 1. All 68 patients with stones shown on imaging and 2 without stones underwent surgery, with good clinical results. Total removal of the SMG and its duct was performed in patients with multiple stones, chronic inflammatory changes in the SMG, or a solitary stone in the SMG or deep in the duct. A small incision for removal of a solitary stone in the distal aspect of Wharton's duct was performed in 15 patients, with excellent clinical results. Another 14 patients with multiple salivary gland stones, diagnosed on CT reconstructions, did not improve following this procedure and needed further surgery; clinical improvement occurred following excision of the SMG and Wharton's duct. Histological examination in all of these confirmed the presence of additional stones. Conservative anti-inflammatory treatment was recommended for 6 patients in whom CT reconstructions did not demonstrate stones.

Adult↗

PubMed1996

L-2-Hydroxyglutaric aciduria: neuropathological correlations and first report of severe neurodegenerative disease and neonatal death.

L-2-Hydroxyglutaric aciduria is a rare organic aciduria associated with neurological and particularly cerebellar abnormalities. These abnormalities developed in childhood or later in all previously described patients. We report a more severe form of L-2-hydroxyglutaric aciduria in which an infant presented shortly after birth with hypotonia, apnoea, and seizures, leading to death in the perinatal period. Computerized tomography scans of the brain at 1 day and 2 weeks of age showed abnormal low density of the cerebellum. Examination of the brain showed brainstem and cerebellar atrophy with neuronal loss and gliosis in an olivopontocerebellar distribution. The diagnosis of L-2-hydroxyglutaric aciduria should be considered in any non-dysmorphic newborn with progressive neurological abnormalities and CNS imaging suggesting low density and size of the cerebellum. The diagnostic consideration is based initially on clinical findings. Conventional urine organic acid analysis reveals the presence of 2-hydroxyglutaric aciduria. Specific diagnosis requires methodologies which distinguish the L- from the D-isomer.

Brain↗

PubMed1996

Impact of preoperative risk and perioperative morbidity on ICU stay following coronary bypass surgery.

Prolonged intensive care unit treatment (> 3 days) contributes to increased health costs and resource utilization. In order to devise strategies to limit intensive care unit stay, and provide cost-effective medical care, it is necessary to identify the pre- and perioperative risk factors of prolonged treatment. Over 100 potential risk variables were collected prospectively in 889 consecutive patients undergoing isolated coronary bypass surgery between 1990 and 1992. The incidence of intensive care unit therapy lasting > 3 days was 6.8%. Univariate statistics identified 23 pre- and perioperative variables that were potential contributors to prolonged intensive care unit therapy. However, multivariate analysis of preoperative risk variables identified only recent myocardial infarction (within 30 days of surgery) and continued preoperative smoking (within 30 days of surgery) to be independent risk factors. Only 6.3% of patients without preoperative myocardial infarction and 6.1% of non-smokers required prolonged intensive care unit treatment, compared with 14.8% of patients with preoperative myocardial infarction (P = 0.01) and 10.1% of smokers (P = 0.07). When multivariate analysis was repeated with both pre- and perioperative variables, only ischemic morbidity (inotropes, myocardial infarction and low-output syndrome; 138 patients) and non-ischemic morbidity (infection, stroke or bleeding; 37 patients) predicted prolonged intensive care unit treatment. Intensive care unit treatment for > 3 days occurred in 26.8% of patients with ischemic morbidity compared with 3.2% of patients without ischemic morbidity (P = 0.001). Prolonged intensive care stay occurred in 32.4% of patients who suffered non-ischemic complications compared with 5.7% of patients who did not suffer these complications. The multiple logistic regression analysis odds ratio for ischemic morbidity was 7.4 (95% c.i. 4.0-13.4) compared with 4.8 (95% c.i. 1.9-10.1) for non-ischemic morbidity. Strategies designed to reduce the incidence of prolonged intensive care unit treatment should include prevention of stroke, infection and bleeding. However, the greatest reduction of intensive care unit utilization would be mediated by prevention of ventricular dysfunction secondary to myocardial ischemia or inadequate myocardial preservation.

Adult↗

PubMed1996

Evaluation of the lacrimal drainage function by the drop test.

PURPOSE: To compare the fluorescein dye disappearance test with a new test for lacrimal drainage capacity, the drop test. METHODS: In the fluorescein dye disappearance test, 1 microliter of fluorescein solution was instilled into the conjunctival sac of normal subjects and of patients with epiphora. Fluorescence from the tear film was measured, and the rate of dye disappearance was calculated as a measure of tear drainage. In the drop test, drops of 10 microliters of lukewarm saline solution were repeatedly instilled into the conjunctival sac for 3 minutes. Excessive saline solution was then removed from the tear film and measured. The volume of saline solution drained by the lacrimal passage could thus be calculated. RESULTS: The fluorescein dye disappearance test showed, in normal subjects, a tear turnover rate of 10.9 +/- 3.1% (95% confidence interval) per minute, which was nor age dependent. The drop test showed a decreased lacrimal drainage capacity with increasing age in normal subjects, with a mean capacity of 150 +/- 38.5 microliters/3 min for those 41 to 80 years old. In patients with indoor epiphora, the fluorescein dye disappearance test values were significantly reduced. However, the fluorescein dye disappearance test could not differentiate among normal eyes, eyes with minor epiphora, or eyes with moderate epiphora. The drop test showed a significant decrease even in patients with minor epiphora and was further decreased with increasing severity of symptoms. CONCLUSION: The drop test provides a quantitative measurement for lacrimal drainage function and is more sensitive than the fluorescein dye disappearance test.

Adolescent↗

PubMed1996

Tumor ploidy as a risk factor for disease recurrence and short survival in surgically treated Dukes' B2 colon cancer patients.

The risk factors for colon cancer recurrence following a curative intent surgery include the tumor location and size, the presence of adhesions, perforation, bowel obstruction, depth of invasion, histological grade, percentage of S phase content and cell kinetic profile. The DNA content of tumor cells has recently been suggested as an additional prognostic factor. In this study we assessed the tumor ploidy as a prognostic factor for recurrence and survival in colon cancer patients. The DNA content of colon cancers in 20 Dukes' B2 patients followed up at our center, who relapsed either locally or systemically, following surgical treatment was measured by image analysis. The data were pair-matched for age, sex, tumor site and grade, and the period of follow-up with 20 Dukes' B2 patients who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients with recurrence, whereas only in 8 (40%) in the control group. Nonaneuploid DNA content was found in 12 (60%) patients of the control group, but in only 4 (20%) patients with a relapse. Aneuploidy was associated with a significantly higher tumor recurrence rate (p = 0.024) and shorter overall survival (p < 0.002). Our data point to a possible indication of a systemic adjuvant chemotherapy in Dukes' B2 colon cancer patients who have aneuploid tumors on image analysis. This should be further investigated in a prospective controlled randomized study.

Aged↗

PubMed1996

Long-term development of lens opacities after exposure to ultraviolet radiation at 300 nm.

The long-term development of lens opacities after short-term exposure to ultraviolet radiation (UVR) was determined. Altogether, 200 Sprague-Dawley rats received unilaterally 5 or 20 kJ/m2 UVR (lambda MAX = 300 nm, lambda 0.5 = 10 nm) in vivo, during 15 min. At 1, 4, 8, 16 and 32 weeks after exposure subgroups of 20 rats from each dose group were sacrificed. Both lenses were removed for measurement of intensity of forward scattered light. It was found that exposed lenses scatter light more than their contralaterals and that a higher dose induces more light scattering. After exposure to 5 kJ/m2, the mean difference in scattering remained unchanged between 1 and 32 weeks' latency, but the distribution of the individual differences in scattering became skew. For several animals, lens opacities induced by 5 kJ/m2 seemed to decrease during the observation period. Earlier observations in complement to current findings implicate that it is optimal to detect close-to-threshold UVR-induced cataract at 1 week after exposure.

Animals↗

PubMed1996

Recognition of hallucinations: a new multidimensional model and methodology.

Both from the clinical and mathematical perspectives, symptom recognition has received less attention than disease recognition. To redress this balance, it is imperative that multidimensional models are constructed for each and all mental symptoms. This paper offers one such model for "hallucinations', and a set of prototypical data comparing the performance of pattern recognition techniques (cluster and discriminant analyses) and neural networks (Kohonen and backpropagation). It is concluded that multidimensional models are less wasteful of information than (current) categorial ones. Because of this and of the fact that symptom structure is likely to be "isomorphic' with the brain region where the corresponding signal is generated, it is recommended that multidimensional models are preferentially used in neurobiological research.

Bipolar Disorder↗

PubMed1996

Albumin gene expression during mouse odontogenesis.

Albumin protein is present in developing teeth of several species. Oligomer primers and cRNA probes specific for albumin were designed to perform RT-PCR, and for in situ hybridization, respectively. In situ hybridization failed to reveal albumin expression in any tooth cells, however, albumin PCR products were amplified from tissues adhering to the roots of developing teeth from four-week-old mice. It is concluded that this source is not the primary source of albumin protein found in developing enamel, because of the location and level of expression of albumin mRNA in periodontal tissue.

Albumins↗

PubMed1996

Combined liver radiation and chemotherapy for palliation of hepatic metastases from colorectal cancer.

PURPOSE: To report the effects of boost dose radiation on palliation, survival, and toxicity in patients undergoing palliative treatment for hepatic metastases from colorectal cancers and to assess the potential benefits of higher doses of radiation to partial liver volumes. MATERIALS AND METHODS: Forty-five patients with hepatic metastases from colorectal cancers were treated with a course of palliative irradiation. Eligible patients included those with radiographically or histologically proven liver metastases. All patients but one received chemotherapy, either pretreatment (one patient) and/or concurrently with radiation (43 patients) via intravenous or hepatic intraarterial infusion. Patients were divided into two groups based on whether or not boost radiation was given. Thirty-three of the 45 patients (group 1) received whole-liver irradiation at doses that ranged from 8 to 31 Gy at 2.0 to 3.0 Gy per fraction (median dose, 21 Gy). The remaining 12 patients (group 2) received liver irradiation to 20 to 30 Gy followed by a boost dose to the area of dominant disease for a total dose of 33 to 60 Gy. The extent of liver involvement was similar between the two groups. Palliation, overall survival, and toxicity were analyzed with respect to radiation dose. RESULTS: There was no increase in acute effects observed in treating partial liver volumes to higher doses in conjunction with systemic chemotherapy. No cases of radiation-induced hepatitis or nephritis were documented. Hematologic toxicity (> or = grade 3) was observed in four patients with thrombocytopenia, three with leukopenia, and two with anemia. Pain was relieved in 71% and hepatomegaly in 59% of group 1 patients, as compared with 100% and 89%, respectively, of group 2 patients. Other symptoms such as nausea, fever, fatigue, and jaundice were palliated in 35% of group 1 and 90% of group 2 patients. The median survival time for group 1 patients was 4 months (range, 1 week to 26 months), which is consistent with that reported in the literature. The median survival time for group 2 patients was 14 months (range, 2 to 32 months) (P=.01). CONCLUSION: Standard hepatic irradiation followed by boost radiation to partial liver volumes in combination with chemotherapy is well tolerated without significant acute/late morbidity. Higher radiation doses to partial liver volumes offers improved palliative benefit and may prolong survival without an increase in morbidity.

Adult↗