Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 379 records · Page 21Linked to original sources

PubMed1998

Effects of hypoxia on renal hormonal balance in normal subjects and in patients with COPD.

There is a complex interaction between pulmonary haemodynamics, hormonal, and salt and water balance in patients with chronic obstructive pulmonary disease (COPD) and in normal subjects exposed to hypoxia or high altitude. This study aims to investigate the effects of hypoxia on renal hormonal balance in normal subjects and patients with COPD, particularly the role of urinary dopamine and atrial natriuretic peptide (ANP). Urinary dopamine output, ANP, and plasma renin activity (PRA) were measured in 12 normal subjects exposed to hypoxia (12% O2) and hyperoxia (40% O2) for 1 h and in 15 patients with exacerbations of COPD while breathing air or O2. These measurements were repeated in six of the patients with exacerbations of COPD when they were clinically stable. Hypoxia caused an increase in ANP levels (49 +/- 6-62 +/- 6 pg ml-1, P < 0.05) and a fall in urinary dopamine output (277 +/- 39-205 +/- 33 ng h-1, P < 0.002) in normal subjects. Hyperoxia was associated with a return of plasma ANP to the baseline values. In patients with exacerbations of COPD plasma ANP levels were higher (181 +/- 36 pg ml-1) than in normal subjects (49.5 +/- 6.5 pg ml-1, P < 0.001). Urinary dopamine output breathing air (175 +/- 34 ng h-1) was similar to the levels when normal subjects were made hypoxaemic and PRA was elevated in comparison to normal values. There was no change in their levels following the acute administration of oxygen in patients presenting with exacerbations of COPD, but oxygen improved urinary sodium excretion (P < 0.05). In six patients re-studied when clinically stable there was a fall in urinary dopamine output, plasma ANP and PRA when breathing air in comparison to the acute stage of the disease (P < 0.05). These data suggest presence of renal hormonal imbalance including endogenous urinary dopamine output during hypoxic exacerbation of COPD and in normal subjects exposed to hypoxia.

Acute Disease↗

PubMed1998

Clinical predictors of nasal secretory cell quantities in allergy clinic patients.

BACKGROUND: Nasal cytograms are useful in evaluating patients with inflammatory disease of the nose and paranasal sinuses. When mucosal samples are taken with curette and brush devices, significant numbers of non-leukocytic cells can also be analyzed. OBJECTIVE: To examine two specific morphologic variations in granule-containing epithelial cells in nasal samples obtained from allergy clinic patients and describe their clinical associations. These two cellular variants consisted of goblet cells, with coalesced granules usually displacing the nucleus, and discrete granular mucinous cells (DGMC), which show more discrete granules not displacing the nucleus. METHODS: Patients from an adult allergy clinic were studied prospectively for nasal mucosal cytology, historical clinical data, nasal physical findings, serum IgE levels, and aeroallergen-specific IgE. Proportions and absolute numbers of goblet cells and DGMC in the nasal mucosal samples were related to other data using simple and multivariate analyses. RESULTS: Both goblet cells and DGMC showed absolute number increases in patients with observable nasal secretions. Discrete granular mucinous cell decreases were also observed in patients with IgE levels greater than or equal to 200 IU/mL and in asthmatic patients. In non-asthmatic patients with nasal eosinophilia, a significantly greater proportion of DGMC was observed compared with other patients (19.8 +/- 11.9% versus 8.5 +/- 5.9%, P = .007), while asthmatics with nasal eosinophilia had mean DGMC quantities closer to that observed in patients without nasal eosinophilia. Increases in goblet cell numbers were observed in patients with specific IgE to aeroallergens compared with other patients (46.5 +/- 46.7 versus 27.0 +/- 23.9, P = .014). Multivariate analysis confirmed that (1) the presence of aeroallergen-specific IgE and (2) the presence of nasal eosinophilia in the absence of asthma were differentially associated with increases in goblet cells and DGMC, respectively. CONCLUSIONS: Increases in nasal DGMC and goblet cells differentially relate to specific clinical patterns of nasal cellular inflammation and aeroallergen hypersensitivity. The nasal epithelial cell profile associated with nasal eosinophilia in asthmatics may differ from that observed in non-asthmatic nasal eosinophilia.

Adult↗

PubMed1998

Non-steroidol anti-inflammatory drug effect on crypt cell proliferation and apoptosis during initiation of rat colon carcinogenesis.

Sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colorectal cancer. However, the optimal drug, period of efficacy and mechanism(s) of action are unknown. Experiments were undertaken to determine which of several NSAIDs would modulate colon crypt cell proliferation or apoptosis when given during the initiation phase of 1,2-dimethylhydrazine (DMH)-induced rat colon cancer. Colon crypts located both away from and over an aggregate of lymphoid nodules (ALN) were examined. Rats were injected with aspirin, indomethacin, nabumetone, sodium salicylate, 16,16-dimethyl prostaglandin E2 or saline for 3 days and DMH or DMH vehicle on day 4 of each week for 8 weeks, then killed 3 days after the last DMH injection. At the time of killing, DMH had significantly increased crypt cell proliferation but not apoptosis. There was significantly more cell proliferation and apoptosis in crypts over the ALN than away from the ALN. Aspirin and salicylate increased proliferation and apoptosis in crypts over the ALN. Finally, the distributional peaks of cell proliferation and apoptosis were shifted significantly closer together after DMH. Thus, DMH increases proliferation and alters the distribution of proliferating and apoptotic cells in colon crypts early in carcinogenesis. Aspirin may suppress tumour incidence via salicylate by enhancing apoptosis in carcinogen-initiated cells.

1,2-Dimethylhydrazine↗

PubMed1998

Autologous CD34-selected blood progenitor cell transplants for patients with advanced multiple myeloma.

Fifty-five patients with advanced multiple myeloma received purified CD34-selected peripheral blood progenitor cell transplants following myeloablative chemotherapy. A median of 4.1 x 10(6) CD34 cells/kg (range 1.2-30.7) were infused after busulfan (14 mg/kg) and cyclophosphamide (120 mg/kg); granulocyte-macrophage colony-stimulating factor was used until hematopoietic recovery. Median time to neutrophils >0.5 x 10(9)/l and platelets >20 x 10(9)/l were 12 days (range 10-16 and 8-184 days, respectively). Median follow-up of survivors from the time of transplantation is 33 months (range 7 to 44 months). Thirty-one patients are alive, 19 progression-free. Median progression-free survival is 14 months. Actuarial 3-year progression-free and overall survival are 29+/-14% and 47+/-17%. CD34-selection of peripheral blood progenitor cells provides effective hematopoietic support with significant progression-free and overall survival.

Adult↗

PubMed1998

Mammalian expression of transmembrane receptors for pharmaceutical applications.

Three mammalian expression systems suitable for expressing recombinant receptors have been described. Each is suited to a different aspect of the study of receptors and their behaviour. IRES-based vectors are ideal for creating stable mammalian cell lines suitable for screening receptors using a signalling readout. Unlike traditional vectors they result in almost 100% of cell lines generated expressing a particular receptor, thus increasing the efficiency of cell line generation and increasing the chance of higher expression-level cell lines being generated. They may also be utilized to express more than one protein of interest, for example it is possible to co-express a particular receptor with a particular signalling protein or trafficking protein from a single RNA, thus ensuring that both are expressed simultaneously in the same cell. The ecdysone-inducible expression system is ideal for studying receptor signalling and behaviour. It is possible to alter receptor expression levels in an identical cellular background thus making it possible to study phenomena such as constitutive receptor activity in the absence of agonist. The SFV expression system is ideal for expressing receptors at high levels of a mammalian cell. It is thus a good system for purifying receptors for structural analysis and for providing material for binding assays. All of the expression systems described above have been demonstrated to express seven-transmembrane receptors with the expected pharmacological and functional profile.

Animals↗

PubMed1998

Indoor environment of residential homes in Hong Kong--relevance to asthma and allergic disease.

BACKGROUND: The prevalence of asthma and allergic disease has been increasing in Hong Kong and environmental factors are thought to play a major role. AIM: To define the distribution of common inhaled allergens and air pollutants inside residential homes in Hong Kong. METHODS: Forty randomly selected residential homes were visited and surveyed. Dust samples were collected from mattress, bedroom floor, lounge room floor and kitchen floor for assays of Der p 1, Fel d 1, and Bla g 2. Nitrogen dioxide (NO2) levels were measured by stationary samplers left in the bedroom, lounge room and kitchen over a 1-week period. RESULT: All 40 homes were apartments in high-rise buildings and the mean age of the homes was 7.6 +/- 4.8 years. Visible dampness and mould patches were present in 27.5% of homes and the main fuel for cooking was gas (97.5%). Der p 1, Fel d 1 and Bla g 2 were detectable in at least 1 niche in over 85% of homes. In particular, all dust samples from mattress and bedroom floor contained Der p 1, and over 50% had levels > or = 2 microg/g. The (geometric) mean Der p 1 level in mattress dust was 8.8 (0.3-157.8) microg/g. Fel d 1 and Bla g 2 were present in low levels throughout the homes with respective (geometric) means of 0.3 (0-3.7) microg/g and 0.1 (0-1.1) Unit/g in mattress dust. NO2 was readily detected in all niches but the highest level was in the kitchen with mean exposure of 48.7 ppb which was 1.5 times higher than that in the bedroom and lounge room. CONCLUSION: Major allergens of mite, cat and cockroach, and NO2 are present in varying quantities in residential homes in Hong Kong. Exposure to these environmental factors could be important in the development of asthma and allergic diseases in susceptible individuals.

Air Pollution, Indoor↗

PubMed1998

Transcription of the rat p53 gene is induced by a 39kDa protein binding to the p53 promoter region during the liver regeneration.

The adult rat liver is normally in a state of growth arrest. However, cell loss such as partial hepatectomy can induce the proliferation of the hepatocytes. Early after partial hepatectomy, the concentration of p53 mRNA increases during the prereplicative phase. In this study, we identified the cis-regulatory element involved in the induced transcription of the rat p53 gene by DNase I footprinting assay. This element had a partial homology to the AP1 recognition motif, but the competition study with AP1 oligonucleotide showed that this element was not the AP1 recognition motif. The molecular weight of the binding protein to this motif was determined as 39 kDa by southwestern blotting analysis. In vitro transcription assay with the competitor containing the binding motif showed that the 39 kDa protein binding to the element was required for the induced transcription of the rat p53 gene during the liver regeneration.

Animals↗

PubMed1998

Variations in posteroanterior stiffness in the thoracolumbar spine: preliminary observations and proposed mechanisms.

BACKGROUND AND PURPOSE: Evaluation of posteroanterior (PA) movement in the spine is commonly used in the clinic, but little is known about the mechanisms involved. The purposes of this study were to examine variations in PA stiffness along the thoracolumbar spine and to investigate possible factors that might determine the pattern of stiffness. SUBJECTS: Twenty-one pain-free volunteers (10 male, 11 female), aged 18 to 41 years (mean age=26.6, SD=7.5), participated. METHODS: Posteroanterior stiffness was measured at 5 locations (L4, L1, T10, T7, T4), together with various subject characteristics. RESULTS: Mean PA stiffness varied among locations, with the greatest stiffness at L4 (13.3 N/mm) and the lowest stiffness at L1 (10.4 N/mm). A relatively small, but important, proportion (22% or less) of the variance in stiffness data at some vertebral levels was accounted for by the variables describing subject characteristics. CONCLUSION AND DISCUSSION: Posteroanterior stiffness varies along the spine in a manner consistent with the nature of support for the spine. The observed pattern of variation of PA stiffness along the spine appears to be influenced by some factors other than those relating to the spine.

Adolescent↗

PubMed1998

The evolution of treatment resistance: biologic implications.

The evolution of resistance of positive symptoms to antipsychotic therapy may represent a valuable means of subtyping schizophrenia. In contrast, resistance of negative symptoms and cognitive function to antipsychotic agents seems to be present from the first episode of psychotic symptoms and does not evolve over time to the same extent. If these findings are validated, this clearly points toward differences in the etiology of these components of schizophrenia. Data from a cohort of 223 patients with unsatisfactory responses to classical antipsychotic therapy are evaluated, at least 60% of whom responded to subsequent treatment with clozapine. Comparisons were made between the subgroups of patients with primary and delayed onset treatment resistance. Both subgroups responded to clozapine therapy, although better response was evident for patients with delayed resistance. The withdrawal of clozapine from patients who had previously been responsive to classical antipsychotic therapy was capable of inducing treatment resistance.

Antipsychotic Agents↗

PubMed1998

Nonneoplastic intramedullary spinal cord lesions mimicking tumors.

OBJECTIVE: We report a group of nine patients with atypical, nonneoplastic intramedullary spinal cord lesions. By retrospectively reviewing these patients, we hoped to elucidate characteristics that would identify these patients as harboring nonneoplastic lesions before surgical intervention. METHODS: We reviewed the histological findings of 212 patients undergoing surgery for intramedullary spinal cord tumors between 1989 and 1994. We identified nine patients with nonneoplastic lesions (4%); case histories and radiographs were reviewed. RESULTS: All patients were evaluated preoperatively using magnetic resonance imaging. The extent of enhancement with gadolinium varied from homogeneous enhancement to no enhancement. All lesions showed marked T2 changes. There was a lack of significant spinal cord expansion associated with the lesions in all cases. All patients underwent surgery. The histology of the surgical specimens showed demyelinating lesions in four patients, sarcoidosis in two patients, amyloid angiopathy in two patients, and a mass of nonneoplastic inflammatory cells of unknown origin in one patient. CONCLUSION: Although it was difficult to antecedently distinguish these lesions from neoplastic spinal cord tumors by case history and physical examination, the most consistent clue was absent or minimal spinal cord expansion on the preoperative magnetic resonance images.

Adolescent↗

PubMed1998

The reliability of catheter-tip transducers for the measurement of intrauterine pressure in the third stage of labour.

In order to assess the reliability of intrauterine pressure measurements in the third stage of labour, catheter-tip transducers were used in 20 women randomly allocated into two groups of 10. In each case in the first group two catheters were tied together and introduced transcervically into the uterine cavity after delivery of the placenta. In each case in the second group two catheters were inserted independently into the same uterine cavity. The active and cumulative active pressures recorded from the pairs of catheters within each uterine cavity were compared. Comparison of individual active pressure readings from separate transducers revealed good agreement whether the catheters were tied together or were separate. Cumulative active pressure was very similar when assessed by each catheter in the same uterus. Intrauterine catheter-tip transducers can be used reliably to measure uterine activity in the third stage of labour although there may be minor contraction by contraction differences in recordings of individual active pressures.

Catheterization↗

PubMed1998

Development and validation of a geriatrics attitudes scale for primary care residents.

OBJECTIVE: To develop and validate an instrument measuring attitudes toward older persons and caring for older patients. DESIGN: Cross-sectional and longitudinal studies. SETTING: An academic medical center. PARTICIPANTS: Initial Study: 121 primary care residents (n = 96), fellows (n = 14), and faculty (n = 11) participated in instrument development in 1995. Longitudinal Study: 95 residents (n = 87) and fellows (n = 8) of the initial cohort participated in the 1996 follow-up study, and 61 of the initial cohort (57 residents and 4 fellows) participated in the 1997 follow-up study. Cross Validation Study: 96 first-year residents (n = 78) and fellows (n = 18) participated in this study. MEASUREMENTS: A 14-item geriatrics attitudes scale was developed. The items were selected from a pool of 37 items administered to the 121 participants in the initial study. RESULTS: The instrument demonstrated high reliability (Cronbach's alpha = .76) and known-groups and construct validity. Attitudes were progressively more positive with more medical training (P < .001), and residents with greater career interest in geriatrics scored higher than those less interested (P = .007). Cross validation results supported the reliability and validity of the instrument. Longitudinal data showed significantly different trends of attitude changes among groups of residents and fellows over a 2-year period. CONCLUSIONS: The 14-item geriatrics attitudes scale developed in this study shows sound reliability, validity, and sensitivity to change among primary care residents. The performance of other groups of medical trainees and the relationship of attitude changes to specific medical training warrant further investigation.

Aged↗

PubMed1998

Amphotericin B in lipid emulsion: stability, compatibility, and in vitro antifungal activity.

Newer formulations of amphotericin B (AmB) complexed with liposomes or lipid suspensions have been developed. Preliminary studies have suggested that AmB in Intralipid (IL) may be as effective as, but less toxic than, conventional formulations of AmB, but few data are available regarding its stability, compatibility, or in vitro antifungal activity. A compatibility study was done to evaluate the effects of AmB concentrations in IL containing either 10 or 20% soybean oil. The effects of temperature, shaking, and AmB and IL concentrations on the stability of AmB-IL suspensions were analyzed by visual inspection and liquid chromatography. The in vitro antifungal activity of AmB-IL, compared to that of AmB alone against reference strains of Candida species was determined by using a broth macrodilution method in accordance with National Committee for Clinical Laboratory Standards guidelines (M27-T). Samples of AmB-IL which were lightly shaken retained more than 90% of the AmB concentration over 21 days when stored at either 4 or 23 degrees C. Varying the AmB concentration did not appear to affect the stability of AmB-IL. However, a precipitate was formed when mixtures with more than 30% lipid as a proportion of the total volume were centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities against reference strains of yeasts. Further pharmacologic and clinical studies with AmB-IL are warranted, although AmB should not be combined with IL in concentrations capable of producing a precipitate.

Amphotericin B↗

PubMed1998

Age-related changes in gastric mucosal repair and proliferative activities in rats exposed acutely to aspirin.

The present study was designed to determine whether there are any age-related changes in the repair of acute gastric mucosal injury induced by aspirin in Fischer 344 rats. We have also examined the influence of aging on gastric mucosal proliferative activities, a major component of gastric mucosal defense and repair mechanisms. Our data demonstrated that aging was associated with significant delays in both resolution of gross mucosal injury and regeneration of the injured gastric mucosa. However, there were no correlations between the regeneration of the injured gastric mucosa and gastric mucosal expression of proliferating cell nuclear antigen and transforming growth factor-alpha immunoreactivities.

Aging↗

PubMed1998

Capturing novel mouse genes encoding chromosomal and other nuclear proteins.

The burgeoning wealth of gene sequences contrasts with our ignorance of gene function. One route to assigning function is by determining the sub-cellular location of proteins. We describe the identification of mouse genes encoding proteins that are confined to nuclear compartments by splicing endogeneous gene sequences to a promoterless betageo reporter, using a gene trap approach. Mouse ES (embryonic stem) cell lines were identified that express betageo fusions located within sub-nuclear compartments, including chromosomes, the nucleolus and foci containing splicing factors. The sequences of 11 trapped genes were ascertained, and characterisation of endogenous protein distribution in two cases confirmed the validity of the approach. Three novel proteins concentrated within distinct chromosomal domains were identified, one of which appears to be a serine/threonine kinase. The sequence of a gene whose product co-localises with splicesome components suggests that this protein may be an E3 ubiquitin-protein ligase. The majority of the other genes isolated represent novel genes. This approach is shown to be a powerful tool for identifying genes encoding novel proteins with specific sub-nuclear localisations and exposes our ignorance of the protein composition of the nucleus. Motifs in two of the isolated genes suggest new links between cellular regulatory mechanisms (ubiquitination and phosphorylation) and mRNA splicing and chromosome structure/function.

Amino Acid Sequence↗

PubMed1998

Sequence of a cDNA encoding mouse ribosomal protein S14.

An involution-induced clone was identified by differential screening from a cDNA library of mouse mammary gland. The clone was identified as full-length cDNA encoding the 40S subunit of ribosomal protein S14 (rps14). Comparison of the deduced amino acid sequence to sequences of rps14 from humans, hamsters, and rats showed a conservation.

Amino Acid Sequence↗

PubMed1998

Tantalum ball position after total hip arthroplasty.

There are several techniques for the accurate measurement of the migration of components after arthroplasty some of which require the operative placement of tantalum balls. We have reviewed the position and migration of these markers in 64 patients after total hip arthroplasty. In 40% of cases, one or more balls was seen to be outside the proximal femur on the postoperative radiograph, although all were considered to be within the bone at operation. In two hips, one ball appeared to have migrated towards the joint, although none was seen within the joint. Misplacement was not related to the experience of the surgeon or the operative approach. Migration analysis which necessitates the insertion of tantalum balls requires careful technique to avoid a potential source of third-body wear. It should probably be used only for research in small series of patients.

Arthroplasty, Replacement, Hip↗

PubMed1998

Transcription of the rat p53 gene is mediated by factor binding to two recognition motifs of NF1-like protein.

In this study we analyzed the ratp53 promoter by electrophoretic mobility shift assay (EMSA) and DNase I footprinting analysis. As a result we identified two protein binding elements (element 1: -296 to -312, element 2: -195 to -219) with sequence homology to each other. The two identified elements bind to the same kind of protein. To identify the protein binding to these elements, competition assays were carried out with double stranded oligonucleotides containing NF1, YY1, and CRE consensus motifs. Only the NF1 consensus motif competed with element 1 and 2. Element 2 is conserved between the rat, human, and mouse p53 promoters, and has an NF1 consensus motif. However, the sequences of element 1 are comparatively variable between the species. Only the element 1 region of the rat p53 promoter has partial homology to the NF1 consensus motif. This suggests that the element 1 is specific for the rat p53 gene. The molecular mass of the binding protein, determined by Southwestern blotting analysis, was 40 kDa, which is different from that of NF1. In EMSA with an anti-NF1 antibody, DNA-protein complexes were neither supershifted nor decreased. The 40 kDa protein was also detected in rat spleen and lung, but not in kidney. The binding protein was purified by sequence-specific DNA affinity chromatography and it was confirmed that the purified protein binds to the two regions. It was also proved that the identified two elements are required for basal level transcription of the rat p53 gene by in vitro transcription assay.

Animals↗