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Biomedical subjects

A Hull

Publications and source records attributed to A Hull.

At least 19 recordsLinked to original sources

RIZ1 repression is associated with insulin-like growth factor-1 signaling activation in chronic myeloid leukemia cell lines.

RIZ1 is a histone methyltransferase whose expression and activity are reduced in many cancers. In chronic myelogenous leukemia (CML), blastic transformation is associated with loss of heterozygosity in the region where RIZ1 is located and with decreased RIZ1 expression. Forced RIZ1 expression in model CML blast crisis (BC) cell lines decreases proliferation, increases apoptosis and enhances differentiation. We characterized molecular mechanisms that may contribute to potential CML tumor suppressor properties of RIZ1. Several RIZ1-regulated genes involved in insulin-like growth factor-1 (IGF-1) signaling were identified using cDNA microarrays. RIZ1 was shown to associate with promoter regions of IGF-1 and to increase histone H3 lysine 9 methylation using chromatin immunoprecipitation assays. IGF-1-blocking antibody was used to demonstrate the importance of autocrine IGF-1 signaling in CML-BC cell line viability. Forced RIZ1 expression in CML-BC cell lines decreases IGF-1 receptor activation and activation of downstream signaling components extracellular signal-regulated kinase 1/2 and AKT. These results highlight the therapeutic potential of inhibiting IGF-1 pathway in the acute phase of CML.

DNA-Binding Proteins↗

Prenatal detection of associated anomalies in fetuses diagnosed with cleft lip with or without cleft palate in utero.

OBJECTIVE: The aim of this study was to determine the prenatal detection rate of associated anomalies in fetuses with a suspected cleft lip with or without cleft palate. METHODS: Fetuses with a suspected cleft lip with or without cleft palate, determined by prenatal ultrasound, were prospectively enrolled. Additional anomalies suspected by ultrasound or genetic testing were recorded. Postnatal outcome was obtained. RESULTS: Forty-five fetuses with a cleft lip with or without cleft palate, diagnosed prenatally with either two-dimensional and/or three-dimensional ultrasound, were studied. Postnatal follow-up revealed that 16 (35.6%) of these 45 fetuses had an additional structural or syndromic abnormality. Of the 37 fetuses with prenatally determined 'isolated' cleft lip with or without cleft palate, eight (21.6%) had an additional malformation identified after delivery. CONCLUSION: In pregnancies complicated by a cleft lip with or without cleft palate, patients should be informed of the risks of associated anomalies, some of which may be undetected prenatally.

Abnormalities, Multiple↗

A monkey model for enterohemorrhagic Escherichia coli infection.

Adult Macaca radiata (n=22) were infected intragastrically with 10(12) Escherichia coli O157:H7 strain 84-01, which produces Shiga toxins 1 and 2. Clinical symptoms and bacterial excretion were documented in each monkey for a specified time period before they were killed. At necropsy, samples were obtained for culture and histologic and ultrastructural examination. Seventeen monkeys had diarrhea: E. coli O157 was isolated from postinfection stool samples from all monkeys and from autopsy cultures for 14 of 22 monkeys. Histologic examination showed attaching-effacing lesions, which appeared at 12 h and persisted for 7 days, in 12 monkeys. Widening of the intercellular spaces, degeneration and vacuolization of the epithelial cells, epithelial tufting, extrusion of epithelial cells, and neutrophilic infiltration were characteristic features seen in 20 of the 22 infected monkeys but not in 4 control monkeys. This monkey model closely parallels the early stages of the disease produced by E. coli O157:H7 and would be useful in the further study of pathogenic mechanisms and prevention methods in enterohemorrhagic E. coli infections.

Animals↗

Sources and impact of artifacts on clinical three-dimensional ultrasound imaging.

The purpose of this paper is to investigate, identify and discuss artifacts and their sources arising in three-dimensional ultrasound (3D US) in clinical practice in order to increase the awareness of clinicians and sonographers with respect to common 3D US artifacts and to use this increased awareness to avoid or reduce the occurrence of misdiagnosis in 3D US studies. Patient 3D US data were acquired using several different scanners and reviewed interactively on the scanner and graphics workstations. Artifacts were catalogued according to artifact origin. Two-dimensional ultrasound (2D US) artifacts were classified whether they were of a B-mode or color/power Doppler origin and their presentation in the original scan planes and the resulting volume re-sliced planes and rendered images was identified. Artifacts unique to 3D US were observed, noted and catalogued on the basis of whether they arose during acquisition, rendering or volume editing operations. Acoustic artifacts identified included drop-out, shadowing, etc. whose presentation depended on the relationship between slice and imaging plane orientation. Color/power Doppler artifacts were related to gain, aliasing, and flash which could add apparent structure or confusion to the volume images. Rendered images also demonstrated artifacts due to shadowing and motion of adjacent structures, cardiac motion or pulsatility of the cardiac septum or vessel walls. Editing artifacts potentially removed important structures. Three-dimensional ultrasound is prone to the same types of artifacts encountered in 2D US imaging plus others unique to volume acquisition and visualization. The consequences of these diagnostically significant artifacts include mimicking of abnormal development, masses, or missing structures thus requiring careful study before reaching a diagnosis.

Artifacts↗

Colonization with enteroadherent, enterotoxigenic and enterohemorrhagic Escherichia coli among day-care center attendees in New Orleans, Louisiana.

BACKGROUND: E. coli strains producing specific virulence factors are frequently cited as causes of pediatric diarrhea in developing areas, although many well children from the same areas are colonized with these organisms. The role of these Escherichia coli in day-care center (DCC)-associated diarrhea in the United States has not been evaluated. METHODS: A cohort of 112 DCC attendees from 5 DCC in urban New Orleans were followed longitudinally with demographic data, biweekly routine stool samples and additional stool samples with episodes of diarrhea. E. coli isolates were routinely saved; diarrhea stool samples were tested to detect enterotoxigenic, enterohemorrhagic and enteroadherent strains; and the prevalence of these E. coli in children with and without diarrhea was investigated. RESULTS: During 225 child months of observation 21 episodes of diarrhea were documented and microbiologic data were available for 18. HEp-2 cell enteroadherent E. coli [mostly enteroaggregative (EAggEC) pattern] were identified in 6 of 18 (33.3%) diarrhea cases vs. 6 of 36 (16.6%) age-matched controls. However, the prevalence of EAggEC was very DCC-specific, with EAggEC found in 12 of 22 routine specimens from a DCC with recent EAggEC-related diarrhea vs. 0 of 11 routine specimens from age-matched children in another DCC without EAggEC-related diarrhea (P=0.002). Enterotoxigenic E. coli were uncommon in both ill and well children, and no enterohemorrhagic E. coli were detected. CONCLUSION: EAggEC were commonly isolated from children with and without diarrhea in certain DCC settings, although we cannot determine whether these strains caused diarrhea. Diarrhea-producing E. coli were not associated with diarrhea in this DCC population.

Adhesins, Escherichia coli↗

Structural and functional analysis of the human neutrophil 1-15 antigen, an Mr 65,000 to 70,000 activation-associated membrane proteinase.

Previous studies with the anti-neutrophil/antichymotrypsin mAb 1-15 have identified an activation-associated, chymotrypsin-like activity within the membrane fraction of isolated human neutrophils (PMN). In the present study, the molecular and biochemical characteristics of mAb 1-15 Ag/proteinase were determined. On casein/acrylamide sizing gels, PMN membrane preparations were found to contain an Mr 58,000 to 84,000 band of Ca2(+)-dependent proteinase activity. Reducing and nonreducing SDS-PAGE of mAb 1-15-affinity-purified membrane proteins demonstrated specific recovery of an enzymatically active Mr 65,000 to 70,000 chymotrypsin-like Ag. The presence of a distinct membrane serine esterase of isoelectric point 6.3/Mr 65,000 to 70,000 was confirmed in active site-labeling experiments with the serine proteinase inhibitor [3H]diisopropylfluorophosphate (DFP). Substrate-affinity chromatography with phe-Sepharose or FMLP-Sepharose provided partial purification of enzyme activity among Mr 65,000 to 70,000 FMLP- or phe-binding proteins. Enzyme inhibition was obtained by incubation with mAb 1-15, DFP, N-carbobenzoxyl-phe-chlormethyl ketone, or PMSF, but not tosyl-amide-phenylethylchlormethyl ketone, bestatin, aprotinin, or phosphoramidon. In HPLC analysis, [3H]DFP labeled proteinase was found to comigrate with one of three FMLP-affinity-labeled membrane peaks, but unlike the FMLP surface receptor the DFP-labeling membrane proteinase was not modified by endoglycosidase F. We conclude that the mAb 1-15 Ag, which appears to play a role in PMN activation, is a distinct, active, Mr 65,000 to 70,000 serine proteinase with affinity for substrate sites containing aromatic amino acids.

Antibodies, Monoclonal↗

Impact of race on renal transplant outcome.

The influence of race on the outcome of cadaver renal transplantation (CRT) continues to be controversial even in the cyclosporine era. The present study examines the effect of race in 343 adult CRT performed from 1/1/82 through 10/1/88 with regard to the incidence of delayed function (DF), graft survival (GS), and patient survival (PS). Blacks constituted 38% of the patients. A history of nephrosclerosis secondary to hypertension was more common in blacks, with 51% (67/130) vs. 8% (17/213) in whites, while glomerulonephritis and Type 1 diabetes mellitus were more common in whites. There was no significant difference in the number of HLA (A,B,DR) matches or DR mismatches between whites and blacks. With azathioprine immunosuppression DF was more common in blacks than in whites, 54% (14/26) vs. 20% (11/55) respectively (P less than 0.01). The higher incidence of DF in blacks than in whites on Aza was associated with a significantly lower dose of intraoperative albumin, 0.25 g/kg vs. 0.44 g/kg, respectively (P less than 0.01). Of the Aza treated black recipients who had DF, 79% (11/14) had graft loss within three months, significantly worse than 25% (3/12) with graft loss when immediate function was present (P less than 0.005). Currently, all patients receive at least 0.80 g/kg of albumin intraoperatively and CsA quadruple induction therapy. With the current regimen, black and white recipients of primary CRT recipients have a comparable low incidence of DF of 18% and 22%, respectively. However, DF remains high among repeat black or white recipients: 33% (10/30) and 57% (8/14), respectively. The incidence of rejection within 30 days was similar for black and white recipients during the Aza and CsA eras, 62% vs. 75% and 34% vs. 42% respectively. GS and PS at three months for blacks on Aza were 54% and 89%, respectively, reflecting the corresponding high incidence of DF. This compares with 71% and 97% GS and PS for whites on Aza. Blacks and whites receiving CsA had equivalent 1-year GS and PS: 76% and 92%, respectively. We conclude that, in our center during the Aza era, blacks had a higher incidence of DF and lower GS than whites. With our current intraoperative fluid replacement and CsA immunosuppression, the incidence of DF and GS and PS are equivalent in black and white recipients.

Azathioprine↗