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Biomedical subjects

G Lee

Publications and source records attributed to G Lee.

At least 271 records · Page 15Linked to original sources
PubMed1991

Familial chylomicronemia (type I hyperlipoproteinemia) due to a single missense mutation in the lipoprotein lipase gene.

Complete deficiency of lipoprotein lipase (LPL) causes the chylomicronemia syndrome. To understand the molecular basis of LPL deficiency, two siblings with drastically reduced postheparin plasma lipolytic activities were selected for analysis of their LPL gene. We used the polymerase chain reaction to examine the nine coding LPL exons in the two affected siblings and three relatives. DNA sequence analysis revealed a single nucleotide change compared with the normal LPL cDNA: a G----A substitution at nucleotide position 680. This transition caused a replacement of glutamic acid for glycine at amino acid residue 142 of the mature LPL protein. Amino acid sequence comparisons of the region surrounding glycine-142 indicated that it is highly conserved among lipases from different species, suggesting a crucial role of this domain for the LPL structure. Expression studies of the mutant LPL cDNA in COS-7 cells produced normal amounts of enzyme mass. However, the mutated LPL was not catalytically active, nor was it efficiently secreted from the cells. This established that the Gly----Glu substitution at amino acid 142 is sufficient to abolish enzymatic activity and to result in the chylomicronemia syndrome observed in these patients.

Amino Acid Sequence↗
PubMed1991

Factors affecting the development of pneumothorax associated with thoracentesis.

This study is a retrospective survey of the variables that may influence the development of pneumothorax after thoracentesis. In a 30-month period, a computer search of hospital records identified 342 thoracenteses, of which 154 were done with conventional techniques by the clinical services, and 188 were done with sonographic guidance. Other factors surveyed included the patients' age, sex, underlying pulmonary disease, and overall clinical condition; the size of the effusion; the type of tap (diagnostic or therapeutic); the amount and type (exudate or transudate) of fluid acquired; and the size of the needles used. The technique used was the most significant single risk factor affecting the development of pneumothorax (18% for clinical vs 3% for sonography-guided thoracenteses). The incidence of pneumothorax decreased when a smaller amount of pleural fluid was aspirated (mean, 246 ml aspirated from patients who did not vs 472 ml from those who did develop pneumothorax) and when thin needles were used (4% pneumothorax with 20-gauge or smaller and 18% with larger than 20-gauge needles). The other factors surveyed did not influence the development of pneumothorax. Our results show that sonography-guided thoracentesis is complicated by pneumothorax significantly less often than is thoracentesis done with conventional techniques. Use of the smallest possible needle and aspiration of the smallest possible amount of fluid will also result in fewer cases of pneumothorax.

Adult↗
PubMed1991

Patient centred medicine--threat or opportunity?

One of the benefits of having medical patronage is that representatives from the Institute of Medical Illustrators get invited to occasions which might otherwise be denied us. One such occasion was the discussion day held in July at the Royal College of General Practitioners. The authors represented the Institute, and in some respects the profession, at this study day on: 'The role of the professions allied to medicine in the delivery of primary health care'. As the day unfolded it became obvious that the emerging structures and power base within the National Health Service would have a significant effect on the role of the Medical Illustrator in the future. This paper presents an overview of the development of the NHS with indications for changes required in our profession.

Economic Competition↗
PubMed1991

[Metastasis in oral squamous cell carcinoma].

A precise evaluation of the presence of metastasis is mandatory in the management of head and neck malignancies. Squamous cell carcinoma is the most common malignant tumor of the oral cavity, representing slightly more than 90% of all oral malignancies. The present study included 330 consecutive patients with oral squamous cell carcinoma seen at the Oral and Maxillofacial Surgery Division of the Department of Dentistry, Veterans General Hospital-Taipei from June 1975 to December 1990. Among these cases, the tongue (31.2%) was the most frequently involved site. According to AJCC staging system, 37.3% of the patients were at stage IV, the highest among stages of patients. The overall incidence of regional lymph node metastasis was 49.4%. The incidence of regional lymph node metastasis was significantly correlated with the location of the primary tumor, especially the low metastatic rate of palate and lip carcinoma (p less than 0.05). Distant metastases were detected in 14 (4.2%) cases. The rate of distant metastasis increased with the advance of staging (6.2% for stage III and IV, p less than 0.05). The lungs were the most common sites of distant metastasis. Due to the poor awareness and socio-economic condition of the patients, a majority of them presented with advanced diseases. The distant metastasis rate was low since all the patients were not kept followed up till death, nor was any autopsy study carried out.

Adult↗
PubMed1991

The four-channel pneumogram in infants with recurring apneas and bradycardias.

The two-channel pneumocardiogram (PCG) is frequently used for evaluating infants at risk for infantile apnea. In this study, the two-channel PCG failed to identify a significant number of symptomatic infants that were diagnosed by a four-channel pneumocardiogram. Nine infants suffering from either apparent life-threatening events (ALTE) or persistent apnea of prematurity were evaluated with two- and four-channel PCGs. The four-channel PCGs consisted of the standard two-channel evaluations, ECG and impedance pneumography, expanded by the addition of pulse oximetry and nasal thermistry. The PCGs were evaluated in a blinded manner by three trained observers. Each PCG was evaluated in both the two- and four-channel mode. A PCG was considered abnormal when any of the following was present: (1) a heart rate deceleration greater than one third of the baseline and lasting more than 8 seconds, (2) an apneic pause, either by impedance or by airflow, of greater than 20 seconds, (3) evidence of obstructive apnea less than 20 seconds but associated with cardiac deceleration, and (4) evidence of oxygen desaturation below 85% and lasting more than 8 seconds. All nine of the infants studied had recurrent apneic episodes at home. The four-channel PCGs were abnormal in all of the infants studied, whereas only four of the two-channel PCGs were abnormal (P less than .02). In this population, over 50% of the infants were incorrectly evaluated by the standard two-channel PCG and correctly identified by the four-channel PCG.

Apnea↗
PubMed1991

cDNA cloning of carboxyl ester lipase from human pancreas reveals a unique proline-rich repeat unit.

We report the isolation and nucleotide sequence of the cDNA for carboxyl ester lipase (CEL) from human pancreas. CEL was purified from human pancreas and microsequence analysis was performed on the amino-terminal and internal peptides. Peptide sequence was used to design oligonucleotide probes for screening a human pancreas cDNA library. Partial length cDNAs for CEL were isolated from the library, and the 5' portion of the cDNA was obtained using the anchored polymerase chain reaction. The deduced amino acid sequence indicates that mature CEL contains 722 amino acids and is synthesized with a 20 amino acid leader peptide. The amino acid sequence is rich in proline (12.2%), with 68% of the proline residues occurring within the final 25% of protein length. This is due to the occurrence of a series of proline-rich tandem repeat units near the carboxyl terminus, and accounts for the previously observed species variation in CEL size and amino acid composition. The primary sequence of CEL shows strong similarity to members of the serine esterase family, including the identical G-E-S-A-G motif at the putative active site. A striking homology also occurs between CEL and acetylcholinesterase and cholinesterase, essential enzymes of the nervous system. Proteins with cholesteryl esterase activity have been detected in extra-pancreatic tissues including liver, intestine, kidney, aorta, macrophage, and in the milk of some species (human, gorilla, cat, dog), but not others (rat, cow). To clarify the structural relationships between these various esterases and CEL, we used the CEL cDNA to study expression in pancreas and liver. CEL mRNA was abundant in pancreas of human and rat, with the human CEL mRNA approximately 300 nucleotides larger than that from rat. CEL mRNA was not detected in human adult or fetal liver, nor in rat liver. These results indicate that CEL is not synthesized in significant amounts in liver, and suggest that the cholesterol esterase activity that has been described in liver may be due to a distinct enzyme, or may be derived from pancreas, as has been proposed for the cholesterol esterase activity in intestine.

Amino Acid Sequence↗
PubMed1990

Hepatocellular cancer development in spleen of syngenic rats after transfer of potential precursor hepatocytes.

An in vitro-in vivo approach was used to examine the effect of selected cell proliferation on the progression to cancer. Liver cells isolated from rat donors with nodular livers were kept for 3 h in vitro, transferred to spleens and livers of syngeneic recipients and assessed at 4 and 10 months for evidence of cancer. Ten months after transfer of one million nodular liver cells (40% were GST-P + hepatocytes) to each of 50 recipients, 13 rats developed 21 hepatocellular cancers in their spleens (11 cancers) and livers. The latency to cancer was shortened by exposure to 2-acetylaminofluorene of the recipient rats at the time of hepatocyte transfer.

2-Acetylaminofluorene↗
PubMed1990

Isolation and characterization of the human hepatic lipase gene.

Overlapping bacterial phage and cosmid genomic clones were isolated spanning an area of approximately 60 kilobases that contains the human hepatic lipase (HL) gene. It is composed of 9 exons spanning approximately 35 kilobases of DNA. The entire coding regions, the 5'-flanking sequences, and the exon-intron junctions were sequenced. The intron positions correspond to those of human lipoprotein lipase and canine pancreatic lipase, supporting the concept that these genes constitute a dispersed gene family of lipases and have evolved by duplication of a common ancestral gene. A region of the HL gene, which displays a significant homology with various other lipolytic enzymes and contains the putative catalytic site serine residue of HL, was encoded by exon 4. A major transcription start site of the human HL gene was located by primer extension analysis, 43 nucleotides upstream of the translation initiation codon. Two possible promoter elements were located 25 and 63 nucleotides upstream of the transcription initiation site: a "TATA" box-like sequence, TAATA, and a sequence found in the promoter region of many liver-specific genes, AGGTTAATTATTAAT. In addition, sequences homologous to glucocorticoid and cAMP-responsive elements were identified in the 5'-nontranscribed region.

Amino Acid Sequence↗
PubMed1990

Potential adverse drug interactions in the emergency room. An issue in the quality of care.

STUDY OBJECTIVE: To determine how often emergency department physicians prescribe medications that can adversely interact with other medications that their patients are already taking, which patients are at highest risk for potential adverse reactions, and which medications most frequently lead to adverse interactions. DESIGN: Survey of elderly persons and other adults seeking care at an emergency department. PATIENTS: Four-hundred twenty-four randomly selected adults seeking care at a university-affiliated hospital emergency department. MEASUREMENTS AND MAIN RESULTS: We evaluated 424 randomly selected visits to a hospital emergency department made by 186 persons over age 65 and 238 younger adults; all of the subjects were discharged without hospital admission. Forty-seven percent of visits led to added medication, and in 10% of the visits in which at least one medication was added, a new medication added a potential adverse interaction. The interactions were determined by a computer program, were reviewed using explicit criteria, and were excluded if of uncertain or trivial clinical significance, rare, or not established for that specific drug. The number of medications used at presentation was the best predictor of whether a potential interaction would be introduced. CONCLUSIONS: In the emergency departments studied, a medication history was recorded on every patient and was available to physicians, but physicians did not routinely screen for potential drug interactions. Further safeguards are needed to protect patients from receiving medications that could produce adverse interactions.

Adult↗
PubMed1990

Comparison of the predicted structure for the activated form of the P21 protein with the X-ray crystal structure.

The predicted conformation and position of the central transforming region (residues 55-67) of the p21 protein are compared with the conformation and position of this segment in a recently determined X-ray crystal structure of residues 1-166 of this protein in the activated state bound to a nonhydrolyzable GTP derivative. We previously predicted that this segment of the protein would adopt a roughly extended conformation from Ile 55-Thr 58, a reverse turn at Ala 59-Gln 61, followed by an alpha-helix from Glu 62-Met 67. We further predicted that this region of the activated protein occupies a position that is virtually identical to corresponding regions in the homologous purine nucleotide-binding proteins, bacterial elongation factor (EF-tu), and adenylate kinase (ADK). We find that there is a close correspondence between the conformation and position of our predicted structure and those found in the X-ray crystal structure. A mechanism for activation of the protein is proposed and is corroborated by X-ray crystallographic data.

Computer Simulation↗
PubMed1990

The structure of the carboxyl terminus of the p21 protein. Structural relationship to the nucleotide-binding/transforming regions of the protein.

The carboxyl-terminal region of the ras oncogene-encoded p21 protein is critical to the protein's function, since membrane binding through the C-terminus is necessary for its cellular activity. X-ray crystal structures for truncated p21 proteins are available, but none of these include the C-terminal region of the protein (from residues 172-189). Using conformational energy analysis, we determined the preferred three-dimensional structures for this C-terminal octadecapeptide of the H-ras oncogene p21 protein and generated these structures onto the crystal structure of the remainder of the protein. The results indicate that, like other membrane-associated proteins, the membrane-binding C-terminus of p21 assumes a helical hairpin conformation. In several low-energy orientations, the C-terminal structure is in close proximity to other critical locales of p21. These include the central transforming region (around Gln 61) and the amino terminal transforming region (around Gly 12), indicating that extracellular signals can be transduced through the C-terminal helical hairpin to the effector regions of the protein. This finding is consistent with the results of recent genetic experiments.

Amino Acid Sequence↗