Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 685 records · Page 38Linked to original sources

PubMed1998

AA line.

BACKGROUND: The transverse skin line of the upper part of the forearm is a common, easily recognized condition; however, this line has not been defined clearly and does not correspond to other previously reported skin lines. Our purpose was to assess the nature and associated conditions of this skin line, and characterize the histopathologic features. METHODS: We examined 1343 healthy Korean people. The persons showing this skin line were evaluated by history and physical examination. Skin biopsy was performed on 10 persons showing this line: on one side at both the lesion and contralateral, non-lesion sites. RESULTS: A total of 480 persons (36.4%) showed this line. The incidence was significantly higher in the female group and in the group between 10 and 19 years of age. Histopathologic examination showed subtle edema, separation and fragmentation of collagen bundles, and vasodilation at the transverse skin line. CONCLUSIONS: We conclude that this skin line represents a newly defined skin line, and propose the term AA line.

Adolescent↗

PubMed1998

Photomechanical transcutaneous delivery of macromolecules.

Transcutaneous drug delivery has been the subject of intensive research. In certain situations, rapid transcutaneous delivery is very desirable. A mechanical (stress) pulse generated by a single laser pulse was shown to transiently increase the permeability of the stratum corneum in vivo. The barrier function of the stratum corneum recovers within minutes. The increased permeability during these few minutes allows macromolecules to diffuse through the stratum corneum into the viable epidermis and dermis. Macromolecules (40 kDa dextran and 20 nm latex particles) were deposited into the skin using a photomechanical pulse generated by a single 23 ns laser pulse. This treatment can potentially be utilized in therapies that currently require occlusive dressings for hours or day(s).

Animals↗

PubMed1998

Natural inhibitors for protein prenyltransferase.

Farnesyl protein transferase (FPT) catalyzes the posttranslational farnesylation of the cysteine residue located in the carboxyl-terminal tetrapeptide of the Ras oncoprotein. Prenylation of this residue is essential for membrane association and cell transforming activities of Ras. Inhibitors of FPT have been demonstrated to inhibit Ras-dependent cell transformation and thus represent a potential therapeutic strategy for the treatment of human cancers (1). In the present study, the inhibitory principles for protein prenyltransferases were isolated and identified from Ganoderma lucidum and garlic. The inhibitors from Ganoderma lucidum were identified as ganoderic acid A and ganoderic acid C by comparison with the reported spectral data. Ganoderic acid A has an IC50 value of 100 microM against FPT and its methyl ester (methyl ganoderate A) has an IC50 value of 38 microM for the same enzyme. These inhibitors appear to be competitive with farnesyl pyrophosphate (FPP), and Ki values of ganoderic acid A and methyl ganoderate A are 54 microM and 20 microM, respectively. The inhibitors from garlic were identified as diallyl thiosulfinate (allicin), methyl allyl thiosulfinate, and allyl methyl thiosulfinate. These inhibitors are more effective against geranylgeranyl protein transferase (GGPT) than FPT and IC50 values of allicin, methyl allyl thiosulfinate, and allyl methyl thiosulfinate for GGPT were 43 microM, 57 microM, and 53 microM, respectively. Methyl allyl thiosulfinate appears to be competitive with geranylgeranyl pyrophosphate (GGPP) and its Ki was determined to be 15 microM. The molecular structures of triterpenes and thiosulfinates are expected to be useful in designing lead compounds for new potent antitumour agents.

3T3 Cells↗

PubMed1998

In vitro antigenotoxic activity of novel ginseng saponin metabolites formed by intestinal bacteria.

Ginseng saponin metabolites produced by human intestinal bacteria were evaluated for antigenotoxic properties by testing their effects on benzo[a]pyrene (B[a]P)-induced mutagenicity and clastogenicity. They include 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH-901), 20-O-(alpha-D-arabinopyranosyl(1-->6)-beta-D-glucopyranosyl]- 20(S)-protopanaxadiol (IH-902) and 20-O-[alpha-D-arabinofuranosyl(1-->6)-beta-D-glucopyranosyl]-20(S)- protopanaxadiol (IH-903). IH-901, IH-902 and IH-903 inhibited the mutagenicity of B[a]P in a dose-dependent manner. In the chromosome aberration assay, IH-901 and IH-903 reduced the frequency of chromosome aberration induced by B[a]P. These results suggest that the ginseng saponin metabolites tested in the present study have potential as chemopreventive agents.

Animals↗

PubMed1998

Mutations in the 1A rod domain segment of the keratin 9 gene in epidermolytic palmoplantar keratoderma.

Palmoplantar keratodermas (PPK) constitute a heterogeneous group of diseases marked by the thickening of palms and soles of affected individuals. They are divided into autosomal dominant and autosomal recessive groups by the mode of transmission. The autosomal dominantly transmitted group is further divided into epidermolytic (EPPK, Voerner) and non-epidermolytic (NEPPK, Unna-Thost) types according to the histopathologic findings. Recent development of molecular approaches has confirmed that EPPK and NEPPK are caused by the mutations in keratin 9 and 1 genes, respectively. We have studied three families of EPPK to find the mutation in the keratin 9 gene. DNA sequence analyses revealed single base changes in sequences encoding the highly conserved 1A rod domain segment of the keratin 9 gene in two of the three families. These mutations caused Arg (CGG) to Glu (CAG; R162Q) and Arg (CGG) to Try (TGG; R162W) substitutions. The same arginine position has been mutated in the keratin 10 gene in epidermolytic hyperkeratosis, the keratin 14 gene in epidermolysis bullosa simplex, and the keratin 9 gene in hereditary EPPK in Western patients. In this study we show that unrelated Korean patients have similar mutations.

Arginine↗

PubMed1998

Induction of oral tolerance in human autoimmune thyroid disease.

Our laboratory has reported suppression of experimental autoimmune thyroiditis in mice by oral feeding with antigen. Based on these data, we considered it possible that oral feeding of animal thyroglobulin (TG) might induce tolerance to antigen in human autoimmune thyroid disease (AITD). Thirteen patients receiving thyroid hormone replacement with synthetic thyroxine (T4) (five patients with Graves' disease, treated with radioiodine 4 to 11 years ago and eight patients with Hashimoto's thyroiditis) were randomly assigned to a test group (switched to replacement with desiccated thyroid from porcine thyroids) and a control group (maintained on synthetic T4). Humoral and cellular immunologic parameters were evaluated in addition to clinical parameters before and every 3 months after the onset of study for a year. At the onset of study, there was no difference in clinical parameters, or humoral and cellular immunity to thyroid autoantigens, except a finding that one thyroid peroxidase (TPO) peptide (100 approximately 119) appeared to stimulate peripheral blood mononuclear cells (PBMC) during in vitro microproliferation assay more in the test group than control group (p = 0.051 by t test). Additionally, almost all of TPO and thyrotropin receptor extracellular domain (TSHR) peptides were slightly more stimulatory to PBMC from the test group than the control group, although this was not statistically significant. After treatment, all variables were analyzed at each time point between groups (t test), and also were analyzed over time in each group (analysis of variance, ANOVA). Among the clinical parameters, thyrotropin (TSH) levels were unchanged and equal. Total serum T4 levels (p < 0.05 at 6 and 12 months after treatment) and free thyroxine indices (FT4I) (p < 0.05 at all time points after treatment) were lower in the test group than the control group. This is an expected result of treatment with desiccated thyroid. We found no change over time nor any difference between groups at time points for titers of antibodies to thyroid autoantigens, ie, human TG, human TPO, and recombinant human TSHR from Escherichia coli. However, cellular immunity, measured by in vitro microproliferation of PBMC to peptides of TPO or TSHR, showed significant differences between groups. At 12 months, stimulatory indices (SI) of PBMC to six peptides, containing the indicated amino acids (764 approximately 95, 100 approximately 119, 110 approximately 129, 261 approximately 275, 441 approximately 448, 708 approximately 727) of 10 TPO peptides, and one peptide (145 approximately 163) of 14 TSHR peptides were lower in the test group than control group (p < 0.05). SI of PBMC to phytohemagglutinin, purified protein derivative from mycobacteria, and tetanus toxoid were not different between groups nor changed over time in any group. In conclusion, treating patients with AITD with an antigen related to the autoantigen TG did not produce changes in humoral immunity parameters, while cellular immunity to certain peptides were apparently suppressed. While the results are both surprising and intriguing, we need more evidence to justify the use of autoantigen as a form of immunospecific therapy in patients with AITD.

Administration, Oral↗

PubMed1998

Aged-rodent models of long-term growth hormone therapy: lack of deleterious effect on longevity.

Studies were carried out to examine the effects of long-term recombinant human growth hormone (GH) therapy on longevity in rodents. In the first study, 150 18-month-old female F344 rats were divided into three groups of 50 rats per group: Group 1, solvent vehicle; Group 2, 10 microg GH/kg body weight three times per week; Group 3, 50 microg GH/kg body weight three times per week. GH and solvent vehicle therapies were started at 18 months of age and continued until all the animals died spontaneously. Serum insulin-like growth factor (IGF)-I was measured at 18 and 29 months of age and on 3-month-old rats. Serum IGF-I level decreased between 3 and 29 months of age. GH therapy reversed the decrease in a dose-dependent manner, with the 50 microg GH dose returning the serum IGF-I level to that of 3-month-old animals. However, statistical analysis revealed no significant effect of GH therapy on median life span, 10th percentile life span, or maximum life span. Similar observations on longevity were made on aged F344 male rats and on aged Balb/c mice, even when the dose of GH was increased to 1.0 mg/kg body weight two times per week. The main pathologic lesions in control animals were nephropathy, cardiomyopathy, leukemia, and testicular interstitial cell tumor; the prevalence of these lesions was not significantly altered by GH therapy. We conclude that long-term low-dose GH therapy that includes doses in the range that is given to humans in clinical trials in GH deficiency and to revert age-related physiologic declines has no overt deleterious effects on longevity and pathology in aged rodents.

Aging↗

PubMed1998

A prospective randomized controlled study comparing the morphological and biochemical responses of the endometrium to two different forms of 'period-free' hormone replacement therapy.

Thirty postmenopausal women were randomized to receive either continuous combined (cc) 2 mg oestradiol valerate and 0.7 mg norethisterone acetate hormone replacement therapy (HRT) daily (15 women) or tibolone 2.5 mg daily (15 women) and were monitored to determine the relationship between the two biochemical markers placental protein 14 (PP14) and the glycoprotein CA125, endometrial histology and occurrence of irregular bleeding after 12 months of treatment. The concentrations of PP14 and CA125 in plasma and uterine flushings before and after therapy were measured and their concentrations were associated with the histology of endometrial biopsies obtained on the same day as venesection and endometrial flushing. The levels of PP14 in uterine flushings were significantly increased after the administration of both types of HRT (P < 0.05 for tibolone and P < 0.001 for ccHRT). However, the concentrations of PP14 found in flushings after ccHRT were considerably greater than those found in flushings after tibolone; levels were increased about 150-fold by ccHRT and 6-fold by tibolone (P < 0.001). Plasma concentration of PP14 after both types of HRT were also significantly raised to a similar degree (P < 0.01). In contrast, the concentration of plasma and uterine CA125 were unchanged by either treatment. Histological analysis of the endometrium from women after 12 months of HRT treatment showed that 86% (6/7) of women on ccHRT had secretory activity as compared to 44% (4/9) women on tibolone (P < 0.05). Women with higher post-HRT uterine PP14 concentration were more likely to have irregular bleeding (P < 0.05). Our studies have shown that endometrial PP14 but not CA125 concentrations are raised to a significant degree by two different forms of period-free HRT regimens. Increased PP14 concentrations in uterine flushing may suggest endometrial stimulation of some form and predict the predilection to irregular bleeding. Thus uterine PP14 concentrations may be used to monitor endometrial responses in women on HRT.

CA-125 Antigen↗

PubMed1998

Secondary structures of synthetic peptides corresponding to the first membrane-contact portion of normal band 3 and its deletion mutant (Southeast Asian ovalocytosis).

The conformations of synthetic peptides corresponding to the first membrane-contact portion from Tyr390 to Lys430 of band 3 (band 3-1a) and the counterpart portion of South-East Asian ovalocytosis (SAO) band 3 (band 3-1b) in lipid bilayers were examined by means of circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy as well as a proteolytic digestion method. The CD and FTIR studies showed that band 3-1a and band 3-1b in a membrane lipid bilayer cannot assume an alpha-helix rich structure but instead assume a beta-structure rich conformation. The proteolytic digestion experiments demonstrated that the cleavage sites of Tyr392 and Phe423 were common to both the model and erythrocyte membranes. Taken together with our previous work, which indicated that the first membrane-contact portion was the portion embedded in the erythrocyte membrane without tight lipid-peptide interactions [Hamasaki et al. (1997) J. Biochem. 122, 577-585], we imply herein that the first membrane-contact portion of band 3 by itself can not assume the ordinary alpha-helix conformation in the membrane lipid bilayers. A proteinase-resistant portion, from Ser402 to Phe423, was observed when liposomes containing band 3-1a were digested with proteinase K, while no proteinase-resistant core portion was found in the case of band 3-1b (DeltaAla400-Ala408). This suggests the crucial role of the deleted portion, from Ala400 to Ala408, in the interaction of the first membrane-contact portion of band 3 with a membrane lipid bilayer.

Amino Acid Sequence↗

PubMed1998

Circulating interleukin-16 in systemic lupus erythematosus.

OBJECTIVE: To investigate the relationship between interleukin (IL)-16 and systemic lupus erythematosus (SLE). METHODS: Serum levels of IL-16 were examined in SLE patients using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum level of IL-16 in the patients was much higher than that in healthy volunteers (P < 0.001). An increase in IL-16 was observed in proportion to the activity of SLE assessed by the SLE Disease Activity Index (SLEDAI) score (P < 0.0001). CONCLUSIONS: Our observations suggest an interaction between disease activity and the production of IL-16 in SLE, and reveal that IL-16 is a useful indicator of disease activity. This is the first report describing the relationship between IL-16 and SLE.

Adolescent↗

PubMed1998

Mechanisms mediating the influence of alcohol on the hypothalamic-pituitary-adrenal axis responses to immune and nonimmune signals.

In the rat, the acute administration of alcohol induces dose-related increases in plasma ACTH and corticosterone levels. This response depends on the delivery of the hypothalamic peptides corticotropin-releasing factor and vasopressin (VP) to the pituitary. On the other hand, exposure to an alcohol diet for 7 to 10 days significantly blunts the hypothalamic-pituitary-adrenal (HPA) axis in response to other homeostatic threats, such as mild electroshocks or immune signals. This decreased response is at least in part due to an attenuated ability of VP to increase ACTH secretion. We have previously shown that nitric oxide (NO) inhibits the pituitary response to VP. We therefore hypothesized that chronic alcohol treatment might increase levels of this gas within the HPA axis, and tested this possibility by determining whether blockade of NO formation might restore a normal pituitary response to VP. We observed that such was the case, and therefore propose that NO participates in the blunted activity of the HPA axis during prolonged exposure to alcohol. Finally, we determined whether alcohol would exert neuroendocrine effects that extended beyond the initial drug treatment. To explore this possibility, we injected rats with alcohol intragastrically for 3 days, then re-exposed them to the drug 3 to 12 days later. Rats pretreated with the vehicle and injected with alcohol several days later showed the expected significant rise in plasma ACTH and corticosterone levels, as well as a marked increase in immediate early genes mRNA levels in the paraventricular nucleus (PVN) of their hypothalamus. In contrast, animals pretreated with alcohol exhibited a blunted hormonal and hypothalamic response during the second drug exposure but, interestingly, retained a normal endocrine response to other signals, such as exposure to electro-footshocks or cytokine injection. We originally thought that this phenomenon of selective endocrine tolerance might be explained by decreased serotonin levels in the PVN. Whereas alcohol indeed decreased concentrations of this neurotransmitter in the PVN, exposure to electroshocks induced similar changes. However, an initial exposure to shocks did not blunt the ability of the HPA axis to be activated by a second shock session, by alcohol or by immune signals (delivered several days later). These results do not support the hypothesis that the decreased HPA axis response to a second alcohol challenge is mediated via decreased serotonin afferents to corticotropin-releasing factor neurons in the PVN.

Adrenocorticotropic Hormone↗

PubMed1998

Tamoxifen downregulates TGF-beta production in keloid fibroblasts.

Keloids occur only in humans and are characterized by fibroblast overproduction of collagen types I and III. Keloid fibroblasts have been shown to make elevated levels of transforming growth factor beta (TGF-beta), a growth factor known to promote extracellular matrix production and fibrosis. Thus, the pathophysiology underlying keloid formation may be driven by the biological activity of TGF-beta. Tamoxifen, a synthetic, nonsteroidal antiestrogen has been shown to inhibit keloid fibroblast proliferation and decrease collagen production. The purpose of this study was to determine if a mechanism by which tamoxifen decreases keloid collagen production is through a downregulation of TGF-beta. Through a luciferase TGF-beta bioassay we found that 4 microM of tamoxifen generated a 49% reduction in total TGF-beta activity and 8 microM generated an 85% reduction compared with controls. Thus we propose that one of the mechanisms by which tamoxifen decreases keloid fibroblast collagen synthesis is by decreasing TGF-beta production.

Cell Culture Techniques↗

PubMed1998

Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children.

OBJECTIVE: Little is known about the validity of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young children. Moreover, the results of the DSM-IV field trials raised concerns that inclusion of the new predominantly hyperactive-impulsive type of ADHD in DSM-IV might increase the likelihood of the diagnosis being given to active but unimpaired preschool and primary school children. METHOD: The validity of DSM-IV criteria for each subtype of ADHD was evaluated in 126 children, aged 4 through 6 years, and 126 matched comparison children. Probands and controls were classified by using structured diagnostic interviews of the parent and a DSM-IV checklist completed by the teacher. RESULTS: Children who met DSM-IV criteria for each subtype of ADHD according to parent and teacher reports differed consistently from controls on a wide range of measures of social and academic impairment, even when other types of psychopathology and other potential confounds were controlled. CONCLUSIONS: When diagnosed by means of a structured diagnostic protocol, all three DSM-IV subtypes of ADHD are valid for 4- through 6-year-old children in the sense of identifying children with lower mean scores on measures of adaptive functioning that are independently associated with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed1998

Epidermolysis bullosa acquisita localized to the face.

A 39-year-old woman had a three-year history of recurrent bullous eruption localized to her left cheek. The diagnosis of epidermolysis bullosa acquisita was confirmed by means of direct immunofluorescence and direct immunoelectron microscopic studies performed on the perilesional salt-split skin. Topical corticosteroid treatment reduced pruritus and bullae formation. This case of localized epidermolysis bullosa acquisita on the face is reminiscent of Brunsting-Perry cicatricial pemphigoid. We also review the previously reported cases of localized epidermolysis bullosa acquisita.

Administration, Topical↗

PubMed1998

Intermittent therapy for melasma in Asian patients with combined topical agents (retinoic acid, hydroquinone and hydrocortisone): clinical and histological studies.

Melasma is a common problem in Asians, but treatments have not been satisfactory. In the present study, we evaluated the efficacy of a new formula containing 0.1% tretinoin, 5% hydroquinone, and 1% hydrocortisone (RHQ) in Korean patients with melasma. Twenty-five Korean females with therapy recalcitrant melasma applied RHQ on their faces for 4 months and were evaluated before and 4 weeks after treatment clinically and histologically. They were also evaluated clinically 4 months after treatment. To minimize unavoidable side effects (erythema or peeling), we applied RHQ twice a week instead of the usual daily application. However, we obtained clinical and histological results comparable to other reports from white populations. Statistically significant depigmentation in clinical and histological studies and increased subepidermal collagen synthesis were observed in this study. These effects were seen as early as 4 weeks after treatment with RHQ. We used mMASI scoring, a modified version of the original MASI, to quantify the effects of RHQ more objectively and easily.

Administration, Topical↗

PubMed1998

Lichen planoporitis: keratosis lichenoides chronica revisited.

We report a 70-year-old woman who over a 7-year period developed a widespread violaceous, reticulate and striate eruption with a keratotic component in a clinical pattern previously described as keratosis lichenoides chronica. Multiple biopsies showed a lichenoid reaction centred over the acrosyringium and eccrine ducts entering the epidermis. The acrosyringeal ducts were surrounded by an epidermis that was associated with saw-tooth acanthosis. The ducts displayed hypergranulosis and keratin plugs that extended into the stratum corneum. In the upper dermis the eccrine ducts showed squamous metaplasia with liquefaction of degeneration of their basal cells as well as apoptotic keratinocytes. The subepidermal acrosyringial zone and the eccrine ducts were associated with lymphocytic inflammation and fibrosis. These histopathological findings may represent the counterpart of lichen planopilaris targeting the eccrine ducts. The clinical features defining keratosis lichenoides chronica probably represents a heterogeneous group of conditions including this distinctive subset of lichen planus which we have termed lichen planoporitis.

Aged↗

PubMed1998

Optimization of intensity modulated beams with volume constraints using two methods: cost function minimization and projections onto convex sets.

For accurate prediction of normal tissue tolerance, it is important that the volumetric information of dose distribution be considered. However, in dosimetric optimization of intensity modulated beams, the dose-volume factor is usually neglected. In this paper we describe two methods of volume-dependent optimization for intensity modulated beams such as those generated by computer-controlled multileaf collimators. The first method uses a volume sensitive penalty function in which fast simulated annealing is used for cost function minimization (CFM). The second technique is based on the theory of projections onto convex sets (POCS) in which the dose-volume constraint is replaced by a limit on integral dose. The ability of the methods to respect the dose-volume relationship was demonstrated by using a prostate example involving partial volume constraints to the bladder and the rectum. The volume sensitive penalty function used in the CFM method can be easily adopted by existing optimization programs. The convex projection method can find solutions in much shorter time with minimal user interaction.

Dose-Response Relationship, Radiation↗

PubMed1998

Isolation and characterization of toluene-sensitive mutants from the toluene-resistant bacterium Pseudomonas putida GM73.

To understand the mechanism underlying toluene resistance of a toluene-tolerant bacterium, Pseudomonas putida GM73, we carried out Tn5 mutagenesis and isolated eight toluene-sensitive mutants. None of the mutants grew in the presence of 20% (vol/vol) toluene in growth medium but exhibited differential sensitivity to toluene. When wild-type cells were treated with toluene (1% [vol/vol]) for 5 min, about 2% of the cells could form colonies. In the mutants Ttg1, Ttg2, Ttg3, and Ttg8, the same treatment killed more than 99.9999% of cells (survival rate, <10(-6)). In Ttg4, Ttg5, Ttg6, and Ttg7, about 0.02% of cells formed colonies. We cloned the Tn5-inserted genes, and the DNA sequence flanking Tn5 was determined. From comparison with a sequence database, putative protein products encoded by ttg genes were identified as follows. Ttg1 and Ttg2 are ATP binding cassette (ABC) transporter homologs; Ttg3 is a periplasmic linker protein of a toluene efflux pump; both Ttg4 and Ttg7 are pyruvate dehydrogenase; Ttg5 is a dihydrolipoamide acetyltransferase; and Ttg7 is the negative regulator of the phosphate regulon. The sequences deduced from ttg8 did not show a significant similarity to any DNA or proteins in sequence databases. Characterization of these mutants and identification of mutant genes suggested that active efflux mechanism and efficient repair of damaged membranes were important in toluene resistance.

Amino Acid Sequence↗