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Biomedical subjects

K M Lee

Publications and source records attributed to K M Lee.

At least 145 records · Page 8Linked to original sources
PubMed1998

Extracellular matrix and pulmonary hypertension: control of vascular smooth muscle cell contractility.

Pulmonary hypertension is characterized by increased vascular resistance due to smooth muscle cell hyper-activity and excess deposition of extracellular matrix (ECM) in the vessel wall. We investigated the possibility that changes in cell-ECM interactions may play an active role in this process by modifying the contractile response of pulmonary vascular smooth muscle (PVSM) cells. Contractility was measured within individual cultured PVSM cells, when resting or stimulated with vasoactive agents, by quantitating changes in stiffness of the cytoskeleton (CSK) using magnetic twisting cytometry (N. Wang, J. P. Butler, and D. E. Ingber. Science 260: 1124-1127, 1993). Control studies confirmed that changes in CSK stiffness closely paralleled alterations in cell contraction and relaxation as measured in response to endothelin-1 (ET-1) and dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP), respectively, in a collagen gel contraction assay. CSK stiffness and contractile tone in cultured PVSM cells increased in direct proportion as the density of fibronectin (FN) coating was raised from 10 to 500 ng/well in 96-well plates. Dibutyryl cGMP had no effect in cells on low FN, although it completely inhibited the FN-dependent increase in CSK stiffness on higher ECM densities. In contrast, ET-1 induced the greatest increase in CSK stiffness on the intermediate FN density (100 ng/well). The reduced sensitivity to ET-1 on high FN was not due to dysfunction of the contractile apparatus nor to changes in protein tyrosine phosphorylation. Taken together, these results show that ECM can modulate PVSM cell contractility and suggest that the changes in ECM observed in hypertensive vessels could play an important role in the etiology of this disease.

Animals↗
PubMed1998

The problem of protocol driven costs in pharmacoeconomic analysis.

The increasing number of economic evaluations of healthcare interventions and of drug therapies in particular has been well documented. Surveys of the quality of studies have demonstrated that standards of conduct of such studies have not similarly increased. Concerns over the standards have led to increased calls that economic analyses be more closely linked to randomised controlled clinical trials (RCT). Seven potential threats to the external validity of results limit the generalisability of studies based on RCTs. One such threat is the existence of protocol driven costs. There are two main types of protocol driven costs. Protocol prescribed costs arise as a result of resource use mandated by the clinical trial design. Protocol derived costs occur when increased clinical investigations mandated by trial protocols lead to atypical disease management. Methods to control for protocol driven costs within pharmacoeconomic study designs are available. Modelling studies can be based on data within clinical trials combined with observational data representing more typical resource use. The adoption of pragmatic clinical trial designs provide greater external validity though reduced internal validity. Refinements to explanatory clinical trials can also lead to reduced protocol driven costs. The extent that current studies control for such costs is unclear due to the lack of transparency in the reporting of study methods. A review of published studies found little consideration of protocol driven costs although in several studies there was evidence of their existence. Future studies conducted alongside RCTs should explicitly address how the issue of protocol driven costs was handled within the study framework.

Economics, Pharmaceutical↗
PubMed1998

Anticardiolipin and anti-beta2-glycoprotein I antibodies in Behcet's disease.

To investigate prevalence of anticardiolipin antibodies (aCL) in patients with Behcet's disease (BD) and to determine whether they are related to anti-beta2-glycoprotein I antibodies (aGPI), we measured aCL and aGPI in 47 patients of BD and 14 patients of systemic lupus erythematosus (SLE). The levels of aCL and aGPI were determined by conventional enzyme immunoassay for both IgG and IgM classes. Twelve (25.5%) patients with BD were positive for IgG or IgM aCL and no patient was positive for aGPI. Eleven (78.6%) patients with SLE were also positive for aCL and among them, 8 (72.7%) patients were positive for aGPI. Positive IgG aCL patients with BD showed lower level of IgG aCL than those with SLE (15.7+/-7.3 vs 34.1+/-16.0 GPL, p<0.05). There was no relation between the presence of aCL in BD and either dinical activity or clinical features. In the patients with BD, aCL are found but it would not be associated with aGPI as they are in patients with SLE. In patients with BD, aCL seem to be authentic aCL unlike those in patients with SLE and may not be related with vascular complications in BD.

Adult↗
PubMed1998

Monitoring of dengue viruses in field-caught Aedes aegypti and Aedes albopictus mosquitoes by a type-specific polymerase chain reaction and cycle sequencing.

Virologic surveillance for dengue through the detection of the prevalent serotype(s) circulating in the human population during inter- and intra-epidemic periods constitutes a reliable sentinel system for dengue outbreaks. We have applied a rapid and sensitive, semi-nested, reverse transcription-polymerase chain reaction (RT-PCR) assay using nonstructural protein 3 gene primers for the type-specific-detection of dengue viruses in artificially infected and in field-caught adult Aedes mosquitoes. In laboratory experiments, the assay was sensitive enough to detect one virus-infected mosquito head in pools of up to 59 uninfected heads. In a prospective field study conducted from April 1995 to July 1996, female adult Ae. aegypti and Ae. albopictus mosquitoes were caught from selected dengue-sensitive areas in Singapore and assayed by RT-PCR. Approximately 20% of 309 mosquito pools were positive for dengue viruses. Of the 23 RT-PCR-positive Ae. aegypti pools (containing 1-17 mosquitoes each), 18 pools (78.3%) were positive for dengue 1 virus. There were 40 RT-PCR-positive Ae. albopictus pools (containing 1-33 mosquitoes each) of which 31 (77.5%) were positive for dengue 1 virus. The predominant virus type responsible for the current dengue epidemic since 1995 was also dengue 1. The geographic locations of the virus-infected mosquitoes correlated with the residences or workplaces of patients within dengue outbreak areas. A total of 43.5% of the positive Ae. aegypti pools and 25.0% of the positive Ae. albopictus pools contained only a single mosquito. Both Aedes species showed similar overall minimum infection rates of 57.6 and 50 per 1,000 mosquitoes. Infected Ae. aegypti were detected as early as six weeks before the start of the dengue outbreaks in 1995 and 1996. However, infected Ae. albopictus appeared later, when the number of cases was increasing. Virologic surveillance by RT-PCR for detecting dengue virus-infected Aedes mosquitoes in the field may serve as an early warning monitoring system for dengue outbreaks.

Aedes↗
PubMed1998

Effects of water dilution, housing, and food on rat urine collected from the metabolism cage.

The objective of the study reported here was to investigate three factors that may affect the amounts of water consumed and urine excreted by a rat in the metabolism cage: water dilution, housing, and food. Young F344/N rats (eight per group) were used for all experiments. Food was withheld from rats before each 16-h urine collection, then rats were transferred into a metabolism cage. For trial A (water dilution), urine was collected from rats supplied with dyed water (0.05%, vol/vol). This was repeated three times over a 2-week period. Dye in water or urine was quantified, using a spectrophotometer. For trial B (housing), rats were individually housed in wire cages for 3 weeks before the first urine collection. Then they were group housed in the solid-bottom cage (four per cage). After 2 weeks of acclimation, urine collection was repeated. For trial C (food), one group of rats was provided with food, the other was not, during urine collection. About 8% of urine samples of small volume (< or = 3 ml) from trial A were contaminated with drinking water up to 13% of volume. The average urine volume associated with individual housing was approximately twice as large as that associated with group housing. When food was provided during urine collection, rats consumed similar amounts of water but excreted significantly smaller amounts of urine than did rats without food. It was concluded that water dilution of a urine sample from a sipper bottle is relatively small; rats individually housed in wire caging before urine collection can consume and excrete a larger quantity of water, compared with rats group housed in solid-bottom cages; and highly variable urine volumes are, in part, associated with lack of access to food during urine collection.

Animals↗
PubMed1998

A review of patients with high-risk carcinoma of the cervix treated with combined surgery and postoperative radiotherapy.

From May 1992 to October 1995, 57 patients with early stage cervical carcinoma were treated with hysterectomy and postoperative pelvic radiotherapy because of the presence of adverse histopathologic features. On prospective follow-up and analysis, the clinical outcome for 50 of these patients showed a pelvic disease control rate of 90.9%, a disease-free survival of 80.6% and an overall survival of 86.3%. Of the 8 relapses, half occurred in the pelvis i.e., 2 in the vaginal vault and 2 in the pelvic side walls. No severe complications were observed, but there was a 20% long-term Radiation Therapy and Oncology Group (RTOG) grade 1 to 2 urinary bladder dysfunctional problem and 28% incidence of suprapubic and/or leg oedema.

Adenocarcinoma↗
PubMed1998

Radiotherapy as local adjuvant treatment for endometrial carcinoma--a review of 45 patients.

Forty-five patients with endometrial carcinoma were treated with local postoperative adjuvant radiotherapy during the period 1992 to 1995. Radiotherapy technique comprised both external beam irradiation as well as high-dose-rate vaginal vault brachytherapy. The 5-year overall survival and relapse-free survival rates were 74% and 73%, respectively and poorly differentiated histology grade was associated with poorer prognosis. Only 1 patient developed an isolated vaginal vault recurrence and another 9 patients relapsed mainly at the distal anatomical sites. The main radiotherapy-related complications were vaginal adhesion and stenosis. Radiotherapy is therefore effective as local adjuvant treatment in reducing risk of local-regional relapse in endometrial carcinoma.

Adenocarcinoma↗
PubMed1997

Changes in the alpha 2-adrenergic receptor subtypes gene expression in rat dorsal root ganglion in an experimental model of neuropathic pain.

We examined changes in expression of genes coding for alpha 2-AR subtypes in the dorsal root ganglion (DRG) in a rat model (spinal nerve ligation) or neuropathic pain. The present study demonstrates that the majority of DRG neurons express alpha 2C-AR mRNA and a small proportion of neurons express alpha 2A-AR mRNA, while few neurons express alpha 2B-AR mRNA in non-operated animals. In addition, alpha 2C- and alpha 2A mRNA levels in the DRG showed a significant decrease and increase, respectively in ligated animals. These findings suggest that alpha 2A- and alpha 2C-ARs in the DRG may play an important role in generating sympathetically maintained neuropathic pain.

Animals↗
PubMed1997

The N-terminal tail of histone H2A binds to two distinct sites within the nucleosome core.

Each of the core histone proteins within the nucleosome has a central "structured" domain that comprises the spool onto which the DNA superhelix is wrapped and an N-terminal "tail" domain in which the structure and molecular interactions have not been rigorously defined. Recent studies have shown that the N-terminal domains of core histones probably contact both DNA and proteins within the nucleus and that these interactions play key roles in the regulation of nuclear processes (such as transcription and replication) and are critical in the formation of the chromatin fiber. An understanding of these complex mechanisms awaits identification of the DNA or protein sites within chromatin contacted by the tail domains. To this end, we have developed a site-specific histone protein-DNA photocross-linking method to identify the DNA binding sites of the N-terminal domains within chromatin complexes. With this approach, we demonstrate that the N-terminal tail of H2A binds DNA at two defined locations within isolated nucleosome cores centered around a position approximately 40 bp from the nucleosomal dyad and that this tail probably adopts a defined structure when bound to DNA.

Animals↗
PubMed1997

Distinct cortical areas associated with native and second languages.

The ability to acquire and use several languages selectively is a unique and essential human capacity. Here we investigate the fundamental question of how multiple languages are represented in a human brain. We applied functional magnetic resonance imaging (fMRI) to determine the spatial relationship between native and second languages in the human cortex, and show that within the frontal-lobe language-sensitive regions (Broca's area), second languages acquired in adulthood ('late' bilingual subjects) are spatially separated from native languages. However, when acquired during the early language acquisition stage of development ('early' bilingual subjects), native and second languages tend to be represented in common frontal cortical areas. In both late and early bilingual subjects, the temporal-lobe language-sensitive regions (Wernicke's area) also show effectively little or no separation of activity based on the age of language acquisition. This discovery of language-specific regions in Broca's area advances our understanding of the cortical representation that underlies multiple language functions.

Adult↗
PubMed1997

In vitro reconstitution and analysis of mononucleosomes containing defined DNAs and proteins.

Increasingly, biochemical analyses of processes that occur within eukaryotic nuclei such as transcription and replication require the construction of specific chromatin substrates. Nucleosome complexes reconstituted in vitro have been key elements in a variety of recent studies of polymerase progression and trans-acting factor binding activities. Reconstituted complexes can be easily constructed from purified components in quantities suitable for biochemical and biophysical studies. In addition, reconstituted mononucleosome complexes exhibit native biochemical and biophysical properties but necessarily contain much less heterogeneity with regard to both protein and DNA components than bulk complexes isolated from natural sources. This review details the protocols for reconstitution of model mononucleosome complexes that contain unique DNA sequences and specifically tailored core histone proteins and describes common pitfalls associated with these procedures.

Animals↗
PubMed1997

Stabilization of osteochondral fractures: an experimental study comparing polyglycollic acid degradable pin with K-wire stabilization in rabbits.

Conventional metal implants may be unsuitable for the stabilization of osteochondral fractures as they may interfere with joint function and eventually require implant removal. We therefore compared the use of biodegradable implants with conventional metal ones in an animal experimental study conducted in skeletally mature rabbits. Biodegradable polyglycollic acids pins (PGA) 1.5 mm in diameter were used to stabilize an osteochondral fragment surgically created in the distal femur of rabbits. In another group of 36 animals, conventional metal K-wire of the same diameter was used for stabilization. The animals were killed at intervals of 3 to 24 weeks. Satisfactory union of the fragments was noted in 92% of the PGA implants as compared with 50% with the metal implants group. No implant migration was seen in the PGA group, while migration was noted in all animals with the metal implants. Histological studies showed that in 80% of the cases fixed with PGA implants, the fragment was viable. In the metal group 33% of the fragments underwent fragmentation and necrosis.

Animals↗
PubMed1997

Long-term oral administration of ginseng extract decreases serum gamma-globulin and IgG1 isotype in mice.

Effects of long-term oral administration of ginseng extract on serum protein profile and immunoglobulin (Ig) isotypes were studied in mice. Ginseng extract was orally administered to healthy female mice for 52 days at doses of 30 and 150 mg/kg per day and serum protein electrophoretograms and Ig isotypes levels were evaluated. Serum level of gamma-globulin was decreased dose dependently to 82% (P < 0.05) and 56% (P < 0.01) of control values at the doses of 30 and 150 mg/kg per day, respectively. Levels of total protein, albumin, alpha2- and beta-globulin fractions, as well as the ratio of albumin to globulin (A/G) did not change significantly. However, the alpha1-globulin level increased by 24% (P < 0.05) at the doses of 30 and 150 mg/kg per day. Among the Ig isotypes, including IgG1, IgG2a, IgG2b, IgG3, IgM and IgA, serum IgG1 was dose dependently decreased to 68% (P < 0.05) of control values at the dose of 150 mg/kg per day without significant changes in other Ig isotypes. As IgG1 isotype is rarely cytotoxic and can act as a blocking antibody, it is suggested that the selective decrease in serum IgG1 induced by ginseng extract without changes in the cytotoxic antibodies such as IgG2a may be helpful for the prevention and inhibition of cancer.

Administration, Oral↗
PubMed1997

Effect of physical exercise on renal response to head-out water immersion.

Head-out water immersion (HOI) induces various renal functional changes, such as diuresis, natriuresis, and kaliuresis. The present study was undertaken 1) to characterize the renal response to HOI in Koreans who routinely ingest high salt diet and 2) to evaluate the impact of exercise on the renal response to HOI. Six healthy male subjects (average Na+ intake of 232 mEq.day-1) were immersed upto the neck in 34.5 degrees C water and rested in a seated position or exercised on a bicycle ergometer for 3 hours. In resting subjects, we observed a reversible increase in urine flow and a decrease in urine osmolality, with no changes in creatinine clearance. The peak urine flow observed during the second hour of immersion was 4-fold greater than the pre-immersion level. The excretion of total osmotic substances rose progressively during the 3-hour immersion, which was accompanied by a similar change in Na+ excretion. The K+ excretion was slightly elevated. The major component of the immersion diuresis was a water diuresis in the early phase and an osmotic diuresis in the late phase of immersion. In exercising subjects, the diuretic and natriuretic responses to HOI were attenuated and the kaliuretic response was potentiated. Blood hemoglobin concentration and plasma levels of renin, ADH, and aldosterone decreased during immersion-rest, but they remained unchanged or increased during immersion-exercise. These results suggest that 1) the cardiac mechanoreceptor-mediated renal responses to HOI are not changed by chronic high salt diet, and 2) excessive urinary sodium and water losses are prevented by exercise during immersion.

Adult↗
PubMed1997

Microsatellite instability in Korean patients with gastric adenocarcinoma.

OBJECTIVES: Microsatellites are short repeated oligonucleotide sequences found throughout the human genome. High mutation rates in microsatellite sequences have been found in tumors from patients with hereditary non-polyposis colorectal carcinoma and some sporadic carcinomas. However, little information is available regarding RER-positive phenotype in gastric carcinomas, particularly in terms of age of onset and other pathologic features, such as histologic types, degree of differentiation, location or stage of the carcinoma. METHODS: To obtain a better understanding of the molecular mechanism of gastric carcinogenesis, microsatellite instability was examined at 6 gene loci (D2S71, D2S119, D3S1067, D6S87, D8S87, D11S905) in 77 gastric carcinomas (40 cases of young patients and 37 cases of elderly patients). RESULTS: RER-positive phenotypes were found in 17 (22.1%) of 77 cases. In young patients (under 40 years) RER-positive phenotype was found in 9 (22.5%) of 40 cases, and in elderly patients 8 (21.6%) of 37 cases. Moderately differentiated carcinoma revealed a significantly high frequency of RER-positive phenotype than well differentiated carcinoma(p < 0.001). Tumors arising from the middle third (p < 0.001) or lower third (p < 0.001) revealed higher frequency of RER-positive phenotype than the tumors arising from the upper third of the stomach. The RER-positive phenotype was not significantly affected by the sex, histologic type or stage of carcinoma. CONCLUSION: RER-positive phenotype occurs frequently in gastric carcinoma, although the frequency of RER-positive phenotype between young and elderly patient was not significantly different. Thus, the acquisition of RER-positive phenotype might be an early event in gastric carcinogenesis.

Adenocarcinoma↗
PubMed1997

Local transmission of Plasmodium vivax malaria in Singapore.

A localised outbreak involving 19 cases and two carriers of vivax malaria was reported at Dairy Farm from May to June 1996. Epidemiological investigations showed that the outbreak was caused by the introduction of two foreign workers with imported relapsing vivax malaria into this malaria-receptive area. Transmission of infection occurred amongst 17 other foreign workers residing in the locality and two local residents staying at a condominium nearby. The outbreak was rapidly brought under control through active case finding, isolation and treatment of infected persons, epidemic vector control measures, and improved drainage to prevent Anopheles maculatus breeding. Were it not for the very thorough epidemiological investigations in this episode, foreign workers and local residents with a recent travel history would have been misclassified as imported and the outbreak missed. Medical practitioners should always consider the possibility of malaria in a foreign worker presenting with fever and notify the case as soon as the disease is suspected.

Animals↗