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Biomedical subjects

L K Lee

Publications and source records attributed to L K Lee.

At least 37 records · Page 2Linked to original sources
PubMed1997

Anterior knee pain in the military population.

Anterior knee pain in our military population consititutes a diagnostic and therapeutic problem that is not always easily solved. In recent years, a better understanding of the biomechanics of the patello-femoral joint has contributed to the successful classification and treatment of many patients. However, the cause of pain remains elusive in a significant subset of patients who show no clinical or radiographic evidence of patellar malalignment and continue to have persistent pain despite adequate physiotherapy. In this article, the classification and approach to anterior knee pain are reviewed. Emphasis is placed on dividing patients into four subsets namely; normal tracking, patellar tilt, patellar subluxation and extra-articular causes of anterior knee pain. A more rational approach to the problem can then be employed and successful rehabilitation and/or surgery can be expected.

Biomechanical Phenomena↗
PubMed1996

Matrix metalloproteinase 2 (gelatinase A) regulates glomerular mesangial cell proliferation and differentiation.

A biologic role for the 72-kDa gelatinase A (matrix metalloproteinase 2; MMP-2), beyond simple extracellular matrix turnover, was evaluated in glomerular mesangial cells. To determine the significance of MMP-2 secretion for the acquisition of the inflammatory phenotype, we reduced the constitutive secretion of MMP-2 by cultured mesangial cells with antisense RNA expressed by an episomally replicating vector or with specific anti-MMP-2 ribozymes expressed by a retroviral transducing vector. The phenotype of the transfected, or retrovirally infected, cells was profoundly altered from the activated state and closely approximated that of quiescent cells in vivo. The prominent differences included a change in the synthesis and organization of the extracellular matrix, loss of activation markers, and a virtually total exit from the cell cycle. Reconstitution with exogenous active, but not latent MMP-2, induced a rapid return to the inflammatory phenotype in vitro. This effect was specific to MMP-2, because the closely related MMP-9 did not reproduce these changes. Furthermore, this pro-inflammatory effect of MMP-2 is dependent upon the active form of the enzyme, which can be produced by an autocatalytic activation process on the mesangial cell plasma membrane. It is concluded that MMP-2 acts directly upon mesangial cells to permit the development of an inflammatory phenotype. Specific inhibition of MMP-2 activity in vivo may represent an alternate means of ameliorating complex inflammatory processes by affecting the phenotype of the synthesizing cells, per se.

Animals↗
PubMed1995

Interferon-gamma and interleukin-10 messenger RNA are up-regulated after orthotopic liver transplantation in tolerant rats: evidence for cytokine-mediated immune dysregulation.

BACKGROUND: Immune regulation requires antigen recognition, signaling, activation, secretion of cytokines, and effector function by lymphocytes. Although there is redundancy in the activation and function of the immune response, some cytokines simultaneously promote and suppress different pathways of immunity. In the experiments reported here we compare cytokine gene expression within liver allografts from tolerant rats with normal and isografted liver tissue. We also compare the secretion of interferon-gamma (IFN-gamma) in the supernatant from mixed lymphocyte cultures by using peripheral blood lymphocytes stimulated against donor antigen. METHODS: Orthotopic liver transplantations were performed using the cuff technique without hepatic artery revascularization. Nonisotopic in situ hybridization (ISH) was used to detect and localize messenger RNA to specific cells within tissue. Antisense DNA probes were generated to interleukin-2 (IL-2), IL-4, IL-10, and IFN-gamma. One-way mixed lymphocyte cultures were set up against irradiated donor splenocytes, and the supernatant was collected to measure IFN-gamma by enzyme-linked immunosorbent assay. RESULTS: Expression of IFN-gamma and IL-10 was up-regulated in tolerant animals versus normal or isografted liver (p = 0.0002 and 0.0001, IFN-gamma and IL-10, respectively). In situ hybridization localized the expression of messenger RNA predominantly to the cytoplasm of the hepatocytes. Levels of IFN-gamma were higher in the supernatant from proliferating peripheral lymphocytes against donor antigen from tolerant animals versus naive control animals. CONCLUSIONS: Expression of IFN-gamma and IL-10 is up-regulated in hepatocytes from allograft tissue after orthotopic liver transplantation. We believe that the up-regulation of IL-10 cross-regulates the effector function of IFN-gamma and supports cytokine-mediated immune dysregulation, which may be a mechanism of tolerance after orthotopic liver transplantation in rats.

Animals↗
PubMed1995

In situ comparison of 665 nm and 633 nm wavelength light penetration in the human prostate gland.

The depth of treatment in photodynamic therapy (PDT) of tumors varies with the wavelength of light activating the photosensitizer. New generation photosensitizers that are excited at longer wavelengths have the potential for increasing treatment depths. Tin ethyl etiopurpurin (SnET2), a promising second-generation photosensitizer is maximally activated at 665 nm, which may be significantly more penetrating than 633 nm light currently used with porphyrins in PDT. The penetration of 665 nm and 633 nm wavelength red light in the prostate gland was compared in 11 patients undergoing prostatic biopsies for suspected prostatic cancer. Interstitial optical fibers determined the light attenuation within the prostate gland. Of the 11 patients, 7 had dual wavelength and 4 had single wavelength studies. The mean attenuation coefficients, mueff, for 665 nm and 633 nm wavelength light were 0.32 +/- 0.05 mm-1 and 0.39 +/- 0.05 mm-1, respectively, showing a statistically significant difference (P = 0.0003). This represented a 22% increase in the mean penetration depth and at 10 mm from the delivery fiber there was 1.8 times as much 665 nm light fluence than 633 nm. The mean mueff at 665 nm for benign and malignant prostate tissue were similar (P = 0.42), however, there was significant interpatient variation (mueff ranging from 0.24 to 0.42 mm-1) reflecting biological differences of therapeutic importance. The enhanced light fluence and penetration depth with 665 nm light should allow significantly larger volumes of prostatic tissue to be treated with SnET2-mediated PDT.

Humans↗
PubMed1995

Endothelial cell injury initiates glomerular sclerosis in the rat remnant kidney.

The development of progressive glomerulosclerosis in the renal ablation model has been ascribed to a number of humoral and hemodynamic events, including the peptide growth factor, transforming growth factor-beta 1 (TGF-beta 1). An important role has also been attributed to angiotensin II (AII), which, in addition to its hemodynamic effects, can stimulate transcription of TGF-beta 1. We postulated that increased glomerular production of AII, resulting from enhanced intrinsic angiotensinogen expression, stimulates local TGF-beta 1 synthesis, activating glomerular matrix protein synthesis, and leads to sclerosis. Using in situ reverse transcription, the glomerular cell sites of alpha-1 (IV) collagen, fibronectin, laminin B1, angiotensinogen, and TGF-beta 1 mRNA synthesis were determined at sequential periods following renal ablation. The early hypertrophic phase was associated with global, but transient, increases in the mRNA for alpha-1 (IV) collagen. No changes were noted for fibronectin, TGF-beta 1, and angiotensinogen mRNAs. At 24 d after ablation, at which time sclerosis is not evident, endothelial cells, particularly in the dilated capillaries at the vascular pole, expressed angiotensinogen and TGF-beta 1 mRNAs, as well as fibronectin and laminin B1 RNA transcripts. By 74 d after ablation angiotensinogen and TGF-beta 1 mRNAs were widely distributed among endothelial and mesangial cells, and were particularly prominent in regions of evolving sclerosis. These same regions were also notable for enhanced expression of matrix protein mRNAs, particularly fibronectin. All receptor blockade inhibited angiotensinogen, TGF-beta 1, fibronectin, and laminin B1 mRNA expression by the endothelium. We conclude that, as a result of hemodynamic changes, injured or activated endothelium synthesizes angiotensinogen, triggering a cascade of TGF-beta 1 and matrix protein gene expression with resultant development of the segmental glomerular sclerotic lesion.

Angiotensin II↗
PubMed1994

The effects of 20 weeks basic military training program on body composition, VO2max and aerobic fitness of obese recruits.

Forty of the most obese recruits going through a 20 weeks Basic Military Training (BMT) program were selected from a cohort of 197 obese recruits. Their TBW, BF, FFW, VO2max, time taken to achieve VT (VTTime) and maximal heart rate (HRmax) were measured before, in the middle, and at the end of the program. The means for each of these variables measured in the 3 occasions were analysed for significant differences with the repeated measures analysis of variance. Variables that achieved significant difference were further analysed for pairwise difference with the post-hoc Tukey test. The critical value was set at p < 0.05. Mean TBW and BF decreased from 108.33 +/- 13.1 kg to 90.82 +/- 12.3 kg (p < 0.001), and 34.3 +/- 1.2% to 23.9 +/- 2.3% (p 0.001) respectively. Mean FW decreased from 37.4 +/- 4.8 kg to 22.0 +/- 4.5 kg (p < 0.001). FFW decreased slightly from a mean of 71.5 +/- 8.6 kg to 69.2 +/- 8.8 kg, which was not significantly different (p > 0.05). Mean VO2max increased from 28.1 +/- 6.3 ml.kg-1.min-1 to 32.1 +/- 5.1 ml.kg-1.min-1 (p < 0.001), and mean VTTime on similar exercise protocol increased from 13.3 +/- 2.7 minutes to 15.8 +/- 3.8 minutes (p < 0.001). Mean HRmax decreased from 183.5 +/- 12.1 beats.min-1 to 177.3 +/- 10.1 beats.min-1 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Insulin-like growth factor-I promotes successful fetal pancreas transplantation in the intramuscular site.

BACKGROUND: Fetal pancreas (FP) has the capacity for exuberant proliferation and engrafts in the safe, accessible intramuscular site. These characteristics make FP transplantation an attractive approach to the treatment of diabetes mellitus. Insulin-like growth factor-I (IGF-I) is an important mediator of growth and maturation of many tissues and has been shown to induce fetal islet proliferation. METHODS: IGF-I was locally administered at a rate of 69 micrograms/kg/day to 0, 2, 4, 8, or 16 FP isografts placed into the thigh muscle of streptozotocin-induced diabetic Lewis rats (blood glucose > 350 mg/dl). RESULTS: Diabetes was reversed in eight of eight animals receiving 16 FP and treated with IGF-I. One of seven animals receiving 16 FP without IGF-I treatment became euglycemic (p = 0.003). Similar improved conversion rates were seen in groups of animals receiving either eight, four, or two FP and treated with IGF-I, compared to groups receiving eight, four, or two FP without IGF-I treatment. Euglycemic recipients had physiologic glucose tolerance. The interval to conversion increased inversely in proportion to the amount of FP tissue transplanted. CONCLUSIONS: These results show that local delivery of IGF-I has potent trophic effects on FP transplanted to the intramuscular site.

Animals↗
PubMed1993

Asymmetric origins of the mature glomerular basement membrane.

Renal plasma filtration is a critical physiologic function that depends upon the precise composition and arrangement of the constituent extracellular matrix proteins within the glomerular basement membrane (GBM). The GBM develops during renal embryogenesis by the fusion of discrete basement membranes produced independently by endothelial and visceral epithelial cells, and, possibly from matrix secreted by the mesangial cells. In the mature animal, however, the epithelial cell has generally been accepted as the sole source of all GBM constituent proteins. Although the final structures and distributions of the component proteins have been defined by histochemical techniques, the individual contributions of the three resident glomerular cell types to the maintenance and turnover of the mature GBM remain uncertain. We report the application of a new technique, in situ reverse transcription (ISRT), for the localization of RNA transcripts of nine major GBM protein components within the closely apposed cells of the glomerulus. Using this technique, we demonstrate that in normal adult rat glomeruli the RNA transcripts for heparan sulfate proteoglycan and the laminin-S chain are primarily expressed by visceral epithelial cells, while Type IV alpha-1 and alpha-2 collagen transcripts were restricted to the endothelial cells in a heterogeneous pattern. RNA transcripts for entactin and the laminin-A and -B2 chains were expressed by all three glomerular cell types, while laminin-B1 and fibronectin transcripts were limited to the mesangium. These findings demonstrate that GBM synthesis in the mature animal is not restricted to the epithelial cell and that all intrinsic glomerular cells contribute to the production of GBM protein components. The ISRT technique also provided the additional, and unexpected, finding that appreciable synthetic heterogeneity exists within individual glomerular cell types.

Animals↗
PubMed1993

Simply marking dentures in the SAF. Singapore Armed Forces.

Forensic dentistry is important to the armed forces and denture markers are useful adjuncts in forensic dental identification. The dental services in the Singapore Armed Forces (SAF) recognise this need and have been marking dentures since 1987. The "inclusion method" chosen for marking dentures in the SAF is described.

Denture Identification Marking↗
PubMed1992

Opposite effects of prefrontal cortex and nucleus accumbens infusions of flupenthixol on stimulant-induced locomotion and brain stimulation reward.

Ventral tegmental area (VTA) stimulation produced conditioned place preferences for stimulation-paired environments the magnitudes of which were dose-dependently reduced by systemic application of the dopamine antagonist, haloperidol (0.0, 0.15, 0.3 mg/kg). Bilateral microinjections of cis-flupenthixol (FLU) into the nucleus accumbens (0.0, 1.0, 5.0 or 10.0 micrograms) also resulted in reductions in the size of stimulation-induced place preferences as well as reductions in the magnitude of the hyperlocomotor response to 1.5 mg/kg (s.c.) D-amphetamine. Comparable microinjections of FLU into the medial prefrontal cortex (PFC) produced diametrically opposite effects: the size of VTA stimulation-induced place preferences was either unaffected (1.0 and 5.0 microgram groups) or slightly increased (10 micrograms group) and amphetamine-stimulated hyperlocomotion was dose-dependently potentiated. These behavioral findings suggest a dopamine-mediated modulatory role for the PFC over reward relevant elements within the nucleus accumbens.

Animals↗
PubMed1991

A study of amblyopia in 18-19 year old males.

During a vision screening of 6,556 National Service pre-enlistees aged 18-19 years at the Medical Classification Centre of Central Manpower Base, 48 subjects were found to have visual acuity of 6/12 or less in one or both eyes in the absence of ocular pathology. The prevalence of amblyopia in this population is 0.73%. Amblyopia was due to anisometropia in 24 cases (50%), strabismus in 9 cases (18.7%), high astigmatism (meridional) in 7 cases (14.5%) and other causes or a combination of factors in 8 cases (16.7%). Strabismic amblyopia is most commonly associated with esotropia. There is a positive association between the severity of amblyopia and the degree of strabismus in strabismic amblyopes. Meridional amblyopia tends to be less severe than most other types of amblyopia. The amblyopes were detected late (average 7-10 years of age) and orthoptic treatment of a small minority of them upon diagnosis was unsuccessful.

Adolescent↗
PubMed1985

Age dependence of freezable and nonfreezable water content of normal human lenses.

The cortex, intermediate zone, and nucleus of 19 normal human lenses between the ages of 3 and 77 yr were investigated. The freezable water content of the lenses was obtained by differential scanning calorimetry. The total water content was measured by vacuum dehydration. The nonfreezable water content was calculated from these two measurements. The total water content of the nucleus and intermediate layers decrease with age, while that of the cortex does not vary appreciably. The nonfreezable water content of all three regions of normal human lenses decreases with age.

Adolescent↗
PubMed1982

Aggressive coseasonal immunotherapy in mountain cedar pollen allergy.

Ninety adults with "mountain cedar" pollen allergy were started on coseasonal immunotherapy regimens in December 1979. At season's end, there were 20 whose starting antigen dose was based on serial dilution end point titration (SDET), 1:2,500 or 1:12,500 weight by volume (w/v); 28 in a "traditional" group started at 1:62,500 w/v; and 28 who had been double-blind placebo control subjects. Injections twice weekly were pushed aggressively toward maintenance. The SDET group received 11 times more antigen than the traditional group; both showed a trend for fewer symptoms than the placebo group. As compared with the other groups, SDET subjects had substantially blunted total and specific IgE responses in season, lower specific IgE level at season's end and less shift of skin end point toward higher dilutions. The findings demonstrate that substantial immunologic effects are possible in the first months of aggressive coseasonal immunotherapy.

Adolescent↗
PubMed1982

A simple pharmacokinetic method for separating the three acetylation phenotypes: a preliminary report.

1 Until recently, phenotyping the N-acetyltransferase enzyme had been restricted to distinguishing the slow acetylators from the rapid. Further separation of the heterozygous rapid phenotype from the homozygous rapid phenotype has only been possible by detailed pharmacokinetic studies using sulphadimidine and necessitating prolonged plasma sampling. 2 A simple method of deriving the basic pharmacokinetic parameters is presented. In this study of ten healthy volunteers, one urine sample and hourly plasma sampling over only 5 h enabled calculation of the total body (TBC) and metabolic clearances (MC) wih enough accuracy to distinguish the three (slow, intermediate and rapid) acetylator phenotypes. The spread of the distribution for the elimination rate constant was however too wide to enable their clear separation.

Acetylation↗