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Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 181 records · Page 10Linked to original sources
PubMed2000

Mesothelial hyperplasia with reactive atypia: diagnostic pitfalls and role of immunohistochemical studies-a case report.

The cytomorphologic features of highly reactive mesothelial cells can be difficult to distinguish from malignant cells. We report on an unusual case of mesothelial hyperplasia in a pericardial effusion. The specimen contained bizarre-shaped cells and large tissue fragments in a patient with a history of lung carcinoma. The atypical cells were negative for CEA and LeuM-1 and positive for cytokeratins (AE1/3) and HBME-1. Strong HBME-1 positivity supported a mesothelial origin of the atypical cells and led to the diagnosis of reactive mesothelium. While HBME-1 cannot be used as the sole marker to establish an mesothelial origin; its use in a immunohistochemistry panel may be useful in individual cases to distinguish reactive mesothelial cells from carcinoma in effusion cytology. Diagn. Cytopathol. 2000;22:113-116.

Adenocarcinoma↗
PubMed2000

The lens membrane skeleton contains structures preferentially enriched in spectrin-actin or tropomodulin-actin complexes.

The spectrin-based membrane skeleton plays an important role in determining the distributions and densities of receptors, ion channels, and pumps, thus influencing cell shape and deformability, cell polarity, and adhesion. In the paradigmatic human erythrocyte, short tropomodulin-capped actin filaments are cross-linked by spectrin into a hexagonal network, yet the extent to which this type of actin filament organization is utilized in the membrane skeletons of nonerythroid cells is not known. Here, we show that associations of tropomodulin and spectrin with actin in bovine lens fiber cells are distinct from that of the erythrocyte and imply a very different molecular organization. Mechanical disruption of the lens fiber cell membrane skeleton releases tropomodulin and actin-containing oligomeric complexes that can be isolated by gel filtration column chromatography, sucrose gradient centrifugation and immunoadsorption. These tropomodulin-actin complexes do not contain spectrin. Instead, spectrin is associated with actin in different complexes that do not contain tropomodulin. Immunofluorescence staining of isolated fiber cells further demonstrates that tropomodulin does not precisely colocalize with spectrin along the lateral membranes of lens fiber cells. Taken together, our data suggest that tropomodulin-capped actin filaments and spectrin-cross-linked actin filaments are assembled in distinct structures in the lens fiber cell membrane skeleton, indicating that it is organized quite differently from that of the erythrocyte membrane skeleton.

Actins↗
PubMed2000

Effects of enzyme inducers or inhibitors on the pharmacokinetics of intravenous parathion in rats.

In order to find what form of hepatic cytochrome P450 (CYP) is involved in the metabolism of parathion to form paraoxon, rats were pretreated with the enzyme inhibitors, such as SKF 525-A and ketoconazole or enzyme inducers, such as dexamethasone, isoniazid, phenobarbital, and 3-methylcholanthrene. Parathion, 3 mg/kg, was infused in 1 min via the jugular vein. In rats pretreated with SKF 525-A or ketoconazole, nonspecific CYP inhibitors, the area under the plasma concentration-time curve from time zero to time infinity (AUC) and total body clearance (Cl) of parathion were significantly greater and slower, respectively, than those in respective control rats, suggesting that parathion was metabolized by CYPs. In rats pretreated with dexamethasone (CYP3A23 inducer), the AUC was significantly smaller (41.5 compared with 52.5 microg min/mL), Cl was significantly faster (72.2 compared with 57.1 mL/min/kg), and the amounts and/or tissue-to-plasma ratios of parathion was significantly (or tended to be) smaller than those in control rats. However, the pharmacokinetic parameters of parathion were not significantly different after pretreatment with other enzyme inducers compared with respective control rats. The above data suggested that parathion was metabolized to paraoxon by dexamethasone-inducible CYP3A23, the induction of which was confirmed by Western blot analysis. This was supported by in vitro intrinsic clearance (Cl(int)) of parathion to form paraoxon in hepatic microsomal fraction; the Cl(int) in rats pretreated with dexamethasone was significantly faster (0.0900 compared with 0.0290 mL/min/mg protein) than that in control rats.

Animals↗
PubMed2000

Effects of nonsteroidal anti-inflammatory drugs on post-operative renal function in adults.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) can play a major role in the management of acute pain in the peri-operative period. However, there are conflicting views on whether NSAIDs are associated with adverse renal effects. OBJECTIVES: The primary objective of this review was to determine the effects of NSAIDs on post-operative renal function in adults. SEARCH STRATEGY: Electronic searches for relevant randomised and quasi-randomised controlled trials in Cochrane Controlled Trials Register, MEDLINE and EMBASE were performed. Attempts were also made to identify trials from citation lists of relevant trials, review articles and clinical practice guidelines. Hand-searching of conference abstracts published in major anaesthetic journals was also performed. SELECTION CRITERIA: The inclusion criteria were randomised or quasi-randomised comparisons of individual NSAIDs with either each other or placebo for treatment of post-operative pain, with relevant post-operative renal outcome measures, in adult surgical patients. DATA COLLECTION AND ANALYSIS: Of the 14 trials that fulfilled the selection criteria for this review, eight trials were relevant with sufficient data for meta-analysis. The data was extracted independently by two reviewers. The primary outcome measure was creatinine clearance within the first two days after surgery. Secondary outcome measures included serum creatinine, urine volume, urinary sodium level, urinary potassium level, fractional excretion of sodium, fractional excretion of potassium, need for dialysis and need for diuretic or dopamine treatment for renal insufficiency. Weighted mean differences for continuous outcomes and relative risk for dichotomous outcomes were estimated. MAIN RESULTS: As a group, NSAIDs reduced creatinine clearance by 18ml/min (95%CI: 6 to 31) and potassium output by 38mmol/day (95%CI: 19 to 56) on the first day after surgery compared to placebo. Serum creatinine clearance increased on the second day after surgery by 15umol/L (95%CI: 2 to 28) compared to placebo. No significant reduction in urine volume during the early post-operative period was found. There was no significant difference in serum creatinine in the early post-operative period between patients receiving ketorolac and diclofenac in one trial. No cases of post-operative renal failure requiring dialysis were described. REVIEWER'S CONCLUSIONS: NSAIDs caused a clinically unimportant transient reduction in renal function in the early post-operative period. NSAIDs should not be withheld from adults with normal pre-operative renal function because of concerns about post-operative renal impairment.

Adult↗
PubMed2000

Gastric mucosa-associated lymphoid tissue lymphoma: implications of animal models on pathogenic and therapeutic considerations--mouse models of gastric lymphoma.

There are a number of Helicobacter species that will readily colonise the mouse stomach for the duration of the animal's life. They are Helicobacter felis, "Helicobacter heilmannii" and Helicobacter pylori. Early studies on long-term infection of BALB/c mice showed the presence of lesions resembling low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because of the suggestion that H. pylori was the cause of these tumors in humans, this phenomenon was studied further as it was reasoned that the Helicobacter-infected mice would provide a valuable model of the human disease. Low-grade gastric MALT lymphomas have been shown to follow infection with all the Helicobacter species listed above. These lesions are indistinguishable from the human disease with the presence of centrocyte-like cells, characteristic lymphoepithelial lesions and glandular destruction. Treatment with antimicrobial therapy results in regression of the lymphomas. There is evidence of progression to high-grade in some animals. The Helicobacter mouse models of lymphoma are likely to provide important information relevant not just to H. pylori-induced lesions in the human, but to antigen-driven tumors in general.

Animals↗
PubMed2000

Variability of tear protein levels in normal young adults: between-day variation.

BACKGROUND: An adequate knowledge of physiological variation is important for valid comparative studies of tear proteins. The aim of this study was to investigate the between-day variation of the human tear protein levels, including the total protein concentration (TPC) and the levels of major protein fractions. Two sampling methods, the yawn and the eye-flush methods, were used and compared. METHODS: TPC was determined by the Bradford method. The major protein fractions were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and their levels were determined by scanning densitometry after SDS-PAGE. The tear protein levels were monitored for 3 days. RESULTS: The between-day differences in the levels of TPC and the individual protein fractions were not statistically significant in either sampling method, but the variations of some proteins were large and would be clinically significant. Different variations were observed in different proteins. The variations in serum albumin were large, up to 61% and 113% in the yawn and eye-flush methods respectively. The variations in lactoferrin, tear-specific prealbumin and lysozyme were relatively small in the yawn method. The variations in protein levels obtained by the eye-flush method were generally higher than by the yawn method. CONCLUSION: Although the between-day differences in tear protein levels were not statistically significant, the variations in some proteins would be large in magnitude. The variability of tear protein levels obtained by the eye-flush method was larger than that by the yawn method. Therefore, caution should be taken if the eye-flush method is used for sampling tears for quantitative analysis of tear proteins, although it is easier to collect tear samples using this method. The results will be useful to exclude normal variation in tear protein levels when comparing pre- and post-therapeutic tear protein levels in eyes treated for tear-related abnormalities.

Adult↗
PubMed2000

Indwelling catheters for the management of malignant ascites.

Paracentesis is widely employed for palliation of symptomatic malignant ascites. In some patients, there is rapid re-accumulation of fluid necessitating frequent repeat procedures. Indwelling peritoneal drainage catheters can provide more durable symptom relief, avoiding the hazards and disadvantages of multiple repeat procedures. The goal of our study was to evaluate the technical success, complications and outcome associated with the use of these drainage catheters. We carried out a retrospective review of all patients who had indwelling catheters inserted for the management of symptomatic malignant ascites over a 4-year period. A total of 45 catheters were inserted in 38 patients. Insertion was technically successful in all patients, with immediate symptomatic relief. However, 2 cases of fatal hypotension were encountered in the first 24 h after catheter insertion (acute catheter-related mortality rate of 4.4%). These were attributed to rapid drainage of peritoneal fluid, although gastrointestinal tract bleeding was contributory in the second patient. Eight patients were lost to follow-up. Of the remaining 30, 13 (35.1%) patients developed catheter-related sepsis. The rate of infection was 1.6 episodes per 100 catheter-days. Thirteen tubes were removed prematurely, 6 (16.2%) due to sepsis, 5 (13.5%) because of tube blockage and 2 (5.4%) because of loculated ascites. The median length of time for which catheters were functional was 37 days (95% CI 14.1-59.6), with an average daily drainage of 539.5 ml (range 18-4000 ml). In conclusion, indwelling peritoneal drainage catheters provide a useful alternative to paracentesis in the management of symptomatic malignant ascites. Although it avoids the need for repeated paracentesis, it is not without risks. We discuss and propose some precautions to be observed in the use of these catheters.

Adult↗
PubMed2000

Mother rats bar-press for pups: effects of lesions of the mpoa and limbic sites on maternal behavior and operant responding for pup-reinforcement.

This series of studies explored the operant response rates for pup-reinforcement of female Sprague Dawley rats that were either postpartum or cycling and sustained lesions of the medial preoptic area (mpoa), the lateral amygdala, the nucleus accumbens, or sham lesions. The last experiment tested the effects on operant responding of preventing direct access to pups in mpoa and sham-lesioned postpartum mothers. All animals were trained prior to mating on an FR-1 bar-press schedule to criterion (50 presses in 30 min) for a food (Froot Loops) reward in an operant chamber. At the end of pregnancy animals that were to be tested postpartum were provided in their home cages with six newborn foster pups; mother-litter interactions were observed on the last 3 days of pregnancy and throughout the postpartum period. On each of these same days after a period of separation from pups, females were tested in the operant box for delivery of rat pups. With each bar-press response, a rat pup rather than a Fruit Loop was delivered down a gentle shoot into the hopper. Non-postpartum, but maternal, multiparous animals who were showing estrous cycles were tested using the same procedures. The first and second studies showed that animals (both postpartum and as cycling multiparous animals) with mpoa lesions exhibited a significant reduction in bar-press rate for pup reinforcement in the operant box. In postpartum animals, amygdala lesions also produced a bar-press deficit, whereas nucleus accumbens lesions did not. All lesioned groups showed deficits in maternal responding in the home cage and deficits in retrieval in the operant box. These results indicate that systems associated with the mpoa mediate both the stereotypical maternal behaviors and pup-reinforcement. In contrast, the expression of home cage maternal behavior is dependent on the integrity of both the amygdala and nucleus accumbens, whereas operant responding need not be. These results indicate a dissociation of mechanisms mediating expression of the species-typical maternal behavior and pup-reinforcement.

Amygdala↗
PubMed2000

Factors associated with non-urgent utilization of Accident and Emergency services: a case-control study in Hong Kong.

Accident and Emergency Departments (A&E) have been a popular source of primary care, and studies have shown that up to two thirds of patients attending A&E have problems that could be managed by general practitioners (GPs). Although many studies have found that patients of lower socio-economic class with less social support have a higher utilization rate of A&E, some recent studies have revealed contrary evidence. In this study 2410 patients were randomly selected from four A&E at different times. The gold standard in differentiating true emergency cases and GP cases was based on a retrospective record review conducted independently by a panel of emergency physicians. Two emergency physicians reviewed each case independently, and if their independent ratings were in agreement, this became the gold standard. Patients classified as GP cases were given a telephone interview, and a sample was selected and matched with cases from general out patient clinics (GOPC) in the public sector by morbidity. Reasons for not attending a private GP included closure of clinic, deterioration of symptoms, GPs' inability to diagnose properly, and patients' wish to continue medical treatment in the same hospital. Reasons why non-urgent patients did not choose to attend the nearby public GOPC included affordability, closure of the GOPC, patients' wish to continue treatment at the same hospital, GOPC too far away, no improvement shown after visits to GOPC doctors, and GOPC doctors' inability to make proper diagnoses. The reasons for high level of utilization of A&E services are complex and reflect problems of delivery of GP services. There is an urgent need for GPs to set up a network system to provide out of hours services, and also for a better interfacing between primary and secondary care, and between public and private sectors, so that patients can be referred back to GPs. Interim clinical services provided to those non-urgent cases by nursing practitioners or by GPs working in A&E could also facilitate discharge of patients to primary care facilities.

Adolescent↗
PubMed2000

Management of elderly diabetic patients in the subacute care setting.

Type 2 diabetes is a commonly encountered condition in the subacute care setting. The results of the landmark UK prospective studies have confirmed that aggressive glycemic and blood pressure control delayed diabetes-related microvascular and macrovascular complications and significantly improved diabetic outcomes. Within the past few years, new drugs have been developed to address both aspects of the type 2 diabetes syndrome: insulin resistance and insulin secretory defect. C-peptide analysis may be useful to predict a successful response to therapy with insulin sensitizers or the need to initiate therapy with insulin or insulin stimulators. The issues regarding the general approach to elderly diabetics and the strategies of dealing with diabetic complications encountered in the subacute care program are discussed and updated. It is hoped that diabetic management can be improved and that suggested alternate therapies can be used in the subacute care facilities.

Aged↗
PubMed2000

Essential roles of Drosophila RhoA in the regulation of neuroblast proliferation and dendritic but not axonal morphogenesis.

The pleiotropic functions of small GTPase Rho present a challenge to its genetic analysis in multicellular organisms. We report here the use of the MARCM (mosaic analysis with a repressible cell marker) system to analyze the function of RhoA in the developing Drosophila brain. Clones of cells homozygous for null RhoA mutations were specifically labeled in the mushroom body (MB) neurons of mosaic brains. We found that RhoA is required for neuroblast (Nb) proliferation but not for neuronal survival. Surprisingly, RhoA is not required for MB neurons to establish normal axon projections. However, neurons lacking RhoA overextend their dendrites, and expression of activated RhoA causes a reduction of dendritic complexity. Thus, RhoA is an important regulator of dendritic morphogenesis, while distinct mechanisms are used for axonal morphogenesis.

Animal Structures↗
PubMed2000

Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis.

Metastasis is a frequent complication of cancer, yet the process through which circulating tumor cells form distant colonies is poorly understood. We have been able to observe the steps in early hematogenous metastasis by epifluorescence microscopy of tumor cells expressing green fluorescent protein in subpleural microvessels in intact, perfused mouse and rat lungs. Metastatic tumor cells attached to the endothelia of pulmonary pre-capillary arterioles and capillaries. Extravasation of tumor cells was rare, and it seemed that the transmigrated cells were cleared quickly by the lung, leaving only the endothelium-attached cells as the seeds of secondary tumors. Early colonies were entirely within the blood vessels. Although most models of metastasis include an extravasation step early in the process, here we show that in the lung, metastasis is initiated by attachment of tumor cells to the vascular endothelium and that hematogenous metastasis originates from the proliferation of attached intravascular tumor cells rather than from extravasated ones. Intravascular metastasis formation would make early colonies especially vulnerable to intravascular drugs, and this possibility has potential for the prevention of tumor cell attachment to the endothelium.

Animals↗
PubMed2000

Expression of DNA topoisomerase IIalpha in thyroid neoplasia.

Topoisomerase II (topo II) is an enzyme that affects replication, transcription, and chromosome segregation. It serves as a target for several useful antichemotherapeutic agents, such as etoposide (VP-16) and teniposide (VM26). Monoclonal antibody topo IIalpha (Clone JH2.7; Neomarkers, Union City, CA) specifically identifies the alpha isoform of topo II. Using this antibody in an immunohistochemical analysis, we studied differential expression of topo II in a variety of thyroid lesions. The topo II labeling index is defined as the number of topo II staining positive nuclei divided by the total number of tumor cells counted multiplied by 100. An average of 1,000 cells were counted in each case. The average labeling indexes for anaplastic carcinoma (7.8), tall cell variant of papillary carcinoma (4.8), follicular carcinoma (2.6), Hürthle cell carcinoma (3.4), and medullary carcinoma (2.4) were much higher than for papillary carcinoma (0.76), follicular adenoma (0.65), Hürthle cell adenoma (0.32), and normal thyroid (0.1). This study suggests that immunohistochemical analysis of topo II correlates with thyroid tumor histology; it is more frequently expressed in tumors that are associated with aggressive clinical behavior. It may help to define a role for anti-topoisomerase drugs in treatment of aggressive thyroid neoplasms.

Adenocarcinoma↗
PubMed2000

Bax expressed from a herpes viral vector enhances the efficacy of N,N'-bis(2-hydroxyethyl)-N-nitrosourea treatment in a rat glioma model.

N,N'-bis(2-hydroxyethyl)-N-nitrosourea (BCNU) is a commonly used agent for treatment of malignant gliomas. The mechanisms of cell death and the role of Bcl-2 and Bax in a BCNU-treated rat glioma cell line were investigated. Our results indicate that apoptosis occurs only at a high concentration of BCNU with elevated levels of Bax and a reversed ratio of Bax/Bcl-2. Overexpression of Bax delivered by a herpes simplex viral vector in combination with BCNU chemotherapy enhanced the efficacy of BCNU in a rat glioma model. These findings suggest that conventional treatment with BCNU may be combined with gene therapy that delivers a bax gene into the glioma cells to achieve a high level of Bax, facilitating BCNU-induced cytotoxicity.

Animals↗
PubMed2000

Review article: Helicobacter pylori vaccines-the current status.

In this review, we take a look at the current status in the development of a vaccine against the human pathogenic bacterium, Helicobacter pylori, a major aetiological factor in peptic ulcer disease and gastric adenocarcinoma. Various animal models are now in use from mice infected with H. pylori, through gnotobiotic pigs and primates to ferrets naturally infected with their own Helicobacter, H. mustelae. A significant problem remains the requirement for a suitable mucosal adjuvant. Detoxification or the use of low doses of adjuvants already available may provide a solution and new immune stimulating compounds have been tested with some success. New approaches include the delivery of Helicobacter antigens by DNA immunization, microparticles or live vectors such as attenuated salmonella and the examination of alternative routes of vaccine administration. The phenomenon of post-immunization gastritis and improvements in vaccine efficacy are also discussed. A major area of interest is the mechanism by which immunization actually influences Helicobacter colonization. This remains a mystery: antibodies appear to be unimportant whereas CD4+ T-cells essential. Finally, a viewpoint is given on whom should be immunized when a final vaccine becomes available.

Animals↗
PubMed2000

Detection of a novel campylobacter cytotoxin.

The culture filtrates from 10 Campylobacter species were screened for the presence of cytotoxins on a variety of selected tissue culture cell lines. Some Campylobacter jejuni strains showed no effects on tissue culture cell lines compared with other C. jejuni strains, especially C. jejuni 81116, which consistently produced a cytotoxin that was lethal to tissue culture cells. It was observed that CHO cells were the most sensitive cell line in detecting campylobacter cytotoxins. Samples containing the culture filtrate of C. jejuni 81116 prepared at various growth stages were used to determine the subcellular location of the cytotoxin. This C. jejuni 81116 cytotoxin appears to be a heat-stable toxin that is secreted from the cell during stationary phase; cytotoxin activity can be abolished with proteolytic enzymes.

Animals↗
PubMed2000

Lipopolysaccharide structures of Helicobacter pylori genomic strains 26695 and J99, mouse model H. pylori Sydney strain, H. pylori P466 carrying sialyl Lewis X, and H. pylori UA915 expressing Lewis B classification of H. pylori lipopolysaccharides into glycotype families.

This study describes the molecular makeup of the cell-wall lipopolysaccharides (LPSs) (O-chain polysaccharide-->core oligosaccharide-->lipid A) from five Helicobacter pylori strains: H. pylori 26695 and J99, the complete genome sequences of which have been published, the established mouse model Sydney strain (SS1), and the symptomatic strains P466 and UA915. All chemical and serological experiments were performed on the intact LPSs. H. pylori 26695 and SS1 possessed either a low-Mr semi-rough-form LPS carrying mostly a single Ley type-2 blood-group determinant in the O-chain region covalently attached to the core oligosaccharide or a high-Mr smooth-form LPS, as did strain J99, with an elongated partially fucosylated type-2 N-acetyllactosamine (polyLacNAc) O-chain polymer, terminated mainly by a Lex blood-group determinant, connected to the core oligosaccharide. In the midst of semi-rough-form LPS glycoforms, H. pylori 26695 and SS1 also expressed in the O-chain region a difucosylated antigen, alpha-L-Fucp(1-3)-alpha-L-Fucp(1-4)-beta-D-GlcpNAc, and the cancer-cell-related type-1 or type-2 linear B-blood-group antigen, alpha-D-Galp(1-3)-beta-D-Galp(1-3 or 4)-beta-D-GlcpNAc. The LPS of H. pylori strain P466 carried the cancer-associated type-2 sialyl Lex blood-group antigen, and the LPS from strain UA915 expressed a type-1 Leb blood-group unit. These findings should aid investigations that focus on identifying and characterizing genes responsible for LPS biosynthesis in genomic strains 26695 and J99, and in understanding the role of H. pylori LPS in animal model studies. The LPSs from the H. pylori strains studied to date were grouped into specific glycotype families.

Animals↗