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Biomedical subjects

A Raouf

Publications and source records attributed to A Raouf.

At least 19 recordsLinked to original sources

Discovery of osteoblast-associated genes using cDNA microarrays.

Osteoblast maturation is a complex process and involves distinct genotypic changes that are accompanied by specific phenotypic alterations. To identify new bone-related genes in osteoblasts we utilized the high-density mouse GEM1 microarray gene chip from IncyteGenomics, Inc. (St. Louis, Mo). We examined the expression profiles of over 8700 genes during the proliferation (day 3) and the mineralization (day 34) phases of MC3T3-E1 development. More than 8600 genes provided measurable signals. Of these genes, 252 were found to be differentially expressed on days 3 and 34. A large number of these genes have never been previously recognized in the context of osteoblast development. Approximately, 60% of the genes with expressions that were dominant in proliferating osteoblasts consisted of growth-related genes such as TACC3 and Pr22. The expressions of TIS21/BTG2, and a novel gene EST350, were found to peak during the differentiation phase (day 12), suggesting that they may play important roles in osteoblast differentiation. The majority of the genes with expressions that were dominant during the mineralization phase consisted of signal transduction genes and extracellular matrix (ECM) proteins such as lumican and cystatin-C. It is significant that lumican expression could not be detected on day 3, which indicates that this gene may serve as an important marker of postmitotic osteoblasts. The establishment of the expression profiles of these and other genes with various phases of MC3T3-E1 osteoblast development will allow us to distinguish the molecular events at different phases of osteoblast biology.

Animals↗

[Total glossectomy without laryngectomy. Surgical techniques and its controversies].

UNLABELLED: Total glossectomy is the procedure for entire removal of the tongue, practice considered as one of the most mutilating possible done in head and neck surgery. Vital functions altered after tongue resection are: mastication, language and swallowing. It's controversial the role played by total laryngectomy considering the definitive split of respiratory and digestive tracts. Some AA. perform apart both ectomies pending of the suitable rehabilitation. OBJECTIVE: Report of a case of glossectomy recently operated maintaining the larynx and review the several operative steps, the complications until satisfactory swallow was achieved and perusal of literature on this controversial subject.

Aged↗

Spontaneous and inducible apoptosis in oesophageal adenocarcinoma.

The use of neoadjuvant chemoradiotherapy prior to surgery in the treatment of oesophageal adenocarcinoma has increased in recent years, and up to 25% of patients will have a complete pathological response to the neoadjuvant therapy. Many patients will not respond, however, and the knowledge of molecular factors predicting response or resistance to chemoradiotherapy is required to enhance treatment results. An understanding of apoptosis and cell proliferation may be relevant and this study focused on apoptotic indices and cell-cycle related (Ki-67, p53 and bcl-2) protein expression in a cohort of 42 patients with primary oesophageal adenocarcinoma. We documented that apoptosis occurs among viable (proliferating) tumour cells in all adenocarcinoma cases examined in this study. Pre-operative chemoradiotherapy significantly increased apoptosis and significantly decreased cell proliferation (estimated by Ki-67 expression). Immunohistochemically detected p53 and bcl-2 gene products had no regulatory role in the apoptotic process. The cumulative expression of p53 protein is significantly associated with increasing proliferation activity. Evaluation of apoptosis in pre-treatment specimens may have potential utility in predicting the efficacy of treatment. Assessment of the tumours proliferation activity by Ki-67 expression might identify patients who are at risk of developing metastatic disease.

Adenocarcinoma↗

Ets transcription factors and targets in osteogenesis.

Bone formation in vivo is a complex phenomenon whereby recruitment and replication of mesenchymal precursors of osteoblasts, differentiation into preosteoblasts, osteoblasts, and mature osteoblasts ultimately result in the accumulation and mineralization of the extracellular matrix. MC3T3-E1, a clonal osteoblastic cell line, was derived from mouse calvaria and undergoes an ordered and time dependent developmental sequence leading to formation of multilayered bone nodules over a 30 - 35 day period. This developmental pattern is characterized by the replication of preosteoblasts followed by growth arrest and expression of mature osteoblastic characteristics such as matrix maturation and eventual formation of multilayered nodules with a mineralized extracellular matrix. We have found that Ets1 is expressed in proliferating preosteoblastic cells whereas Ets2 is expressed by differentiating and mature osteoblasts. In addition, the expression of Ets1 can be induced in MC3T3-E1 and fetal rat calvaria cells by retinoic acid (RA) which is known to exert profound effects on skeletal growth and development, bone turnover, and induce specific cellular responses in bone cells. Thus the multiple functions of RA in bone cells are likely to be mediated in part by Ets1. Also, Ets2 transgenic mice develop multiple neurocranial, viserocranial, and cervical skeletal abnormalities. Significantly, these abnormalities are similar to the skeletal anomalies found in trisomy-16 mice and in humans with Down's syndrome, wherein the dosage of Ets2 is known to be increased. These results indicate that Ets2 has an important role in skeletal development and that Ets2 overexpression in transgenics is responsible for the genesis of the same type of skeletal abnormalities that are seen in Down's syndrome. Thus the genetic programs regulated by Ets1 and Ets2 may significantly affect the development and differentiation of osteoblasts, and in fact, Ets1 has been shown to interact with the 'quintessential' osteoblast transcription factor CbfA1. This review will examine in detail the role and possible targets of Ets1 and Ets2 in osteoblast differentiation and bone formation.

Animals↗

Involvement of Ets transcription factors and targets in osteoblast differentiation and matrix mineralization.

The osteoblast-like MC3T3-E1 cell line provides an excellent in vitro model of bone development. This system undergoes three orderly time-dependent phases characterized by proliferating preosteoblasts, matrix accumulation by postmitotic differentiating osteoblasts, and mineralization of the matrix, which results in the formation of multilayered bone nodules. The Ets family transcription factors regulate genetic programs that affect the proliferation and differentiation of osteoblasts. Of the eight Ets family transcription factors examined by our laboratory, only Etsl and Ets2 were found to be expressed at significant levels in this osteogenic system. Etsl is expressed in proliferating preosteoblastic cells, whereas Ets2, silent during this phase, is expressed by differentiating and mature osteoblasts. In addition, the expression of Etsl can be induced in MC3T3-E1 and fetal rat calvaria cells by retinoic acid (RA) which is known to exert profound effects on skeletal growth and development and bone turnover and induce specific cellular responses in bone cells. Thus, the multiple functions of RA in bone cells are likely to be mediated in part by Etsl. We show that the expression of Ets2 precedes and then parallels osteopontin expression and that the OPN promoter contains Ets binding sites and is a transcriptional target of Ets2. In order to identify other potential Ets target genes, we analyzed promoter regions of genes revealed by serial analysis of gene expression as present in the differentiation stage. The functional analysis of these genes has the potential to provide much needed information as to their function in osteogenesis and mineralization of the extracellular matrix and in bone-related diseases.

Animals↗

The Ets1 proto-oncogene is upregulated by retinoic acid: characterization of a functional retinoic acid response element in the Ets1 promoter.

The v-ets oncoprotein and its progenitor Ets1 belong to a family of transcription factors that are related by an 85 amino acid conserved DNA binding domain, the ets domain. Ets1 plays important role(s) in control of cell proliferation, differentiation and apoptosis. Abnormal expression of Ets1 could lead to disruption of these processes and contribute to development of malignancy. Retinoic acid (RA) inhibits proliferation, induces differentiation and regulates apoptosis in many different cell types. Here, we demonstrate that RA treatment increases the expression of Ets1 mRNA, but not that of Ets2, Elk1 or Fli1 in MC3T3-E1 cells. Ets1 induction is detectable after 4 h, can be maintained for at least 14 days, and is inhibited by Actinomycin D, which suggests that RA regulation of Ets1 occurs at the transcriptional level. The promoter region of Ets1 contains four retinoic acid response element (RARE) half sites located at -94, -152, -1765 and -2252 from the translation start site. We show that RARbeta is expressed by MC3T3-E1 cells in the presence of RA and demonstrate that it binds to the -94 RARE half site. Furthermore, RA induces transcription of Ets1 promoter-reporter constructs containing this RARE half site.

Cells, Cultured↗

The AU-rich 3' untranslated region of human MDR1 mRNA is an inefficient mRNA destabilizer.

The human multidrug resistance gene MDR1 encodes a membrane-bound protein, referred to as P-glycoprotein, that acts as a pump to extrude toxins from cells. The 3' untranslated region (3'UTR) of the human MDR1 mRNA is very AU-rich (70%) and contains AU-rich sequences similar to those shown to confer rapid decay on c-myc, c-fos, and lymphokine mRNAs. We tested the ability of the MDR1 3'UTR to act as an mRNA destabilizing element in the human hepatoma cell line HepG2. The MDR1 mRNA has an intermediate half-life of 8 h in HepG2 cells compared to a half-life of 30 min for c-myc mRNA. The MDR1 mRNA half-life was prolonged to >20 h upon treatment with the protein synthesis inhibitor cycloheximide. We constructed expression vectors containing the human beta-globin coding region with the 3'UTR from either MDR1 or c-myc. The c-myc 3'UTR increased the decay of the chimeric mRNA, but the MDR1 3'UTR had no effect. We tested the ability of MDR1 3'UTR sequences to compete for interaction with AU-binding proteins in cell extracts; MDR1 RNA probes had a fivefold lower affinity for AU-binding proteins that interact with the c-myc AU-rich 3'UTR. Overall, our data suggest that the MDR1 3'UTR does not behave as an active destabilizing element in HepG2 cells.

3' Untranslated Regions↗

Outpatient clinic's staffing: a case study.

Suggests that the traditional approach for establishing staffing levels in hospital systems is not feasible. Presents steps taken to study the staffing levels in an outpatient clinic of a central hospital. Puts forward recommendations for a periodic evaluation of staffing levels.

Computer Simulation↗

Distribution of O-acetylated sialomucin in the normal and diseased gastrointestinal tract shown by a new monoclonal antibody.

AIMS: To produce and characterise a monoclonal antibody specific for O-acetylated sialomucin and to assess its use in immunohistochemistry on a panel of normal and diseased intestinal tissue samples. METHODS: Mouse monoclonal antibodies were developed following immunisation with highly purified human colonic mucin. One of these (MMM-17) showed strong binding to mucin throughout the normal colon with relative lack of binding to colon cancer tissue. The binding epitope of MMM-17 was then characterised by screening for agglutination activity against a panel of human and animal erythrocytes and by assessment of its binding to a range of normal and chemically treated slot blotted mucins. Further immunohistochemical studies were then performed on formalin fixed, normal, and diseased human intestinal samples. RESULTS: Binding of MMM-17 to slot blotted human colonic mucin was reduced by 38 (SD 14%) (n = 4) by alkali treatment of the mucin, sequential alkali and sialidase treatment completely abolished binding. Sialidase treatment alone, however, caused only an 11 (11%) reduction in binding. MMM-17 failed to agglutinate any human, rabbit, rat or mouse erythrocytes. These findings were compatible with specificity of MMM-17 for sialomucins O-acetylated at the C-7 or C-8 positions on the sialic acid. Strong staining by MMM-17 was found in all goblet cells throughout all 40 normal colonic and rectal samples studied, but staining was absent in seven of 13 colorectal carcinomas. Normal duodenum (n = 16) and normal ileum (n = 3) all showed occasional positive goblet cells. The normal gastric antral mucosa was generally negative B MMM-17, but in all of 15 cases of gastritis with intestinal metaplasia the metaplastic glands were strongly positive for MMM-17. CONCLUSION: Monoclonal antibody MMM-17 has specificity for O-acetylated sialomucins and its binding depends both on the position of O-acetylation and on the adjacent oligosaccharide structure. Preliminary studies using the antibody on archival tissue samples support the previous reports of reduced O-acetylation in colon cancer demonstrated by indirect histochemistry and show the neo-formation of O-acetylated sialomucin in intestinal metaplasia in the stomach.

Animals↗

A study of perceptual motor load as affected by combined manual and decision task characteristics.

This paper presents an experimental study of Perceptual Motor Load (PML) in a Combined Manual and Decision Task (CMDT). The purpose of this study was to compare Michon's scoring method of measuring PML with a new scoring method as affected by a two-stage CMDT under different work-load conditions. The dual task approach, using the simple task of foot tapping as the secondary task, was applied to obtain the quantitative measurement of PML. The experiment consisted of four major conditions, comprised of one of two activations, i.e., either unimanual or bimanual paired with each of the two stimulative repetitions, i.e., either random or sequential. Under each of the four experimental conditions, a central composite design was applied. The design included three levels of information load, three levels of time lag, and three levels of probability distribution of emergency signal occurrences. Twenty male subjects participated in the experiments. No significant difference between the results of both scoring methods was found; however, the new scoring method can contribute a better measure of PML in terms of correlation coefficients between the scores and the performance times.

Adult↗

Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect.

Previous reports of a selective mucin subclass defect in ulcerative colitis have been reassessed using high performance chromatography (Superose 6 and Mono Q) for mucin purification and fractionation coupled with analysis of the fractions obtained using a combination of enzyme linked lectin and mucin antibody assays. Mucin samples purified from snap frozen rectal biopsy specimens obtained from patients with ulcerative colitis (n = 12), Crohn's disease (n = 5), and non-inflammatory bowel disease control subjects (n = 9) were subject to ion exchange chromatography using a continuous 0-0.35 mol/l NaCl salt gradient with a final 2.5 mol/l NaCl step. In all samples the major proportion (mean (SD) 86.7 (8.9)%) of the mucin detectable by wheat germ agglutinin binding eluted between 0.15 and 0.35 mol/l NaCl with no significant difference in elution profile between ulcerative colitis and control subjects. Significant elution of glycoprotein at less than 0.15 mol/l NaCl did occur, however, when a lower molecular weight mucin containing fraction which contained concanavalin A positive (glucose or mannose containing) material was analysed similarly. Similar ion exchange profiles were obtained when (3H)N-acetylglucosamine labelled mucins were studied after tissue culture of rectal biopsy specimens. No significant alteration in the ion exchange profile of purified mucins in ulcerative colitis has been shown in these studies. It is possible that the previously reported relative depletion of mucin subclass IV (eluting with 0.20 mol/l NaCl) may simply have reflected mucin depletion.

Chromatography, Ion Exchange↗

A personal computer-based maintenance management expert system for hospitals.

In this paper a Maintenance Management Expert System (MMES) is developed. This system is suitable for hospitals as well as for manufacturing organizations. This expert system consists of five sections. These are work order management, equipment management, craftsmen management, material and supply control, and monitoring of maintenance activities. In addition the MMES provides several reports that can be utilized for improving maintenance effectiveness.

Expert Systems↗

Prospective randomised trial of laser therapy only and laser therapy followed by endoscopic intubation for the palliation of malignant dysphagia.

Forty six consecutive patients admitted for the relief of malignant dysphagia were prospectively randomised to receive laser therapy only or initial laser therapy followed by endoscopic intubation. Twenty patients were treated in each group with six exclusions. The patients' swallowing ability was assessed before and during the remainder of their life on a 0-4 scale with 0 being normal swallowing and 4 total dysphagia. The patient's quality of life was measured at the same times, using a physician's assessment (QL index) and the patient's own assessment using a linear analogue self assessment (LASA). There was a significant correlation between all the QL index and the LASA scores collected (n = 126; rs = 0.594, p less than 0.001). The mean monthly dysphagia grade correlated with the QL index (rs = 0.433, p less than 0.001) and the LASA (rs = 0.272, p less than 0.002). There was no significant difference in the dysphagia grade before or after treatment in either group. Dysphagia fluctuated more in those treated with the laser only, however, than in those with a tube inserted. There was also no significant difference in the quality of life measured between the two groups of patients. The complication rate (laser only 10%, laser/intubation 40%, p less than 0.05) was significantly higher in intubated patients. The recurrent dysphagia rate (laser only 25%, laser/intubation 45%, NS) was higher in patients treated with intubation, but they required fewer endoscopic procedures. Overall both procedures were effective in relieving dysphagia and in maintaining quality of life. There was no procedure related mortality in either group.

Adenocarcinoma↗

A study on simultaneous symmetrical motions.

Three right handed male subjects performed a simultaneous symmetical task involving the motions of reach and pressing buttons. Simultaneous performance time was investigated at several symmetical locations. The symmetrical locations were defined by the combinations of different levels of separation distance, angle and distance. Three levels of separation distance (3, 9 and 15 inches), seven levels of angle (0, 15, 30, 45, 60, 75 and 90 degrees from the frontal reference plane) and three levels of distance (6.5, 11.0 and 15.5 inches) were applied to both hands equally. It was found that separation distance, angle and distance were significant factors in simultaneous performance. The performance time was increased when the symmetrical angle region was varied from the 0--45 degrees region to the 45--90 degrees region. Specifically, the performance time was at the minimum at 15 degrees of symmetrical angle and at the maximum at 90 degrees of symmetrical angle. In addition, the performance time increased not only as the distance of the moves was increased, but also as the separation distance interval was increased (i.e., the separation distance interval varied from a 3--9 inch interval to a 9--15 inch interval).

Functional Laterality↗