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Biomedical subjects

S M Hwang

Publications and source records attributed to S M Hwang.

At least 37 records · Page 2Linked to original sources

The effects of epidural blockade on the acute pain in herpes zoster.

OBJECTIVE: To evaluate the relief of acute pain and possible preventive effects on postherpetic neuralgia through the use of an epidural blockade in the acute stage of herpes zoster. DESIGN: Prospective, nonrandomized, comparative clinical trial. SETTING: A dermatologic clinic in a university hospital. PATIENTS: Sixty-five consecutive patients with pain due to acute herpes zoster were treated for a 7-day hospitalization period from July 1, 1996, through June 30, 1997. INTERVENTION: The consecutive patients were divided into 2 groups. Group A consisted of 30 patients who were seen from July 1, 1996, through December 31, 1996, and who were treated with intravenous acyclovir (5 mg/kg) for 7 days. Group B consisted of 35 patients who were seen from January 1, 1997, through June 30, 1997, and who were treated with intravenous acyclovir (5 mg/kg) and an epidural blockade for 7 days. The changes in the intensity of pain and the total duration of pain in both groups were assessed for 12 to 18 months. MAIN OUTCOME MEASURES: The number of days required for relief of pain and the total duration of pain. RESULTS: The mean +/- SD number of days required for relief of pain, which was rated on a scale of 100 (worst pain) to 0 (no pain), was significantly fewer in group B than in group A: it took 2.6 +/- 1.1 days to go from 100 to 50 on the relief-of-pain scale in group B, but 3.8 +/- 1.1 days in group A (P = .03), and 12.5 +/- 6.4 days to go from 100 to 10 in group B, but 20.1 +/- 14.6 days in group A (P = .04). The duration of late residual pain was significantly shorter in group B (5.9 +/- 5.8 days) than in group A (11.9 +/- 7.5 days) (P = .03). The total duration of pain was also significantly shorter in group B (18.5 +/- 9.3 days) than in group A (31.6 +/- 17.6 days) (P = .04). CONCLUSIONS: We believe that an epidural blockade combined with an antiviral agent is a very effective treatment modality for the pain of acute herpes zoster, and we recommend its use for the prevention of postherpetic neuralgia, with a view to shortening the total duration of pain, especially late residual pain.

Acute Disease↗

Pincer nail deformity and pseudo-Kaposi's sarcoma: complications of an artificial arteriovenous fistula for haemodialysis.

Pseudo-Kaposi's sarcoma which develops due to arteriovenous fistulae for haemodialysis is relatively well known. In contrast, nail changes associated with pseudo-Kaposi's sarcoma or venous hypertension are rare. We report a novel case of pincer nail deformity associated with pseudo-Kaposi's sarcoma and venous hypertension, complications of an arteriovenous fistula for haemodialysis, and review eight similar cases reported in the literature. Most of the subjects presented with similar findings, having circulatory disturbance due to an arteriovenous fistula and/or increased venous pressure, and swelling, discoloration and papules/nodules of the skin distal to the shunt. Of the nine patients, three had overcurvature of the nails, in which the lateral edge of the nail pressed deeply into the lateral nail fold. Pincer nail deformity associated with pseudo-Kaposi's sarcoma after placement of an arteriovenous fistula may be relatively common and should be recognized as a specific sign of circulatory disturbance due to the arteriovenous fistula.

Arteriovenous Shunt, Surgical↗

Nurse's cap alopecia.

BACKGROUND: Traction alopecia associated with the nurse's cap is a relatively common form of occupational hair loss. METHODS: We examined 199 healthy South Korean nurses to assess the clinical and pathologic characteristics of traction alopecia caused by prolonged traction exerted at the point of attachment of the nurse's cap. RESULTS: Seven nurses (3.5% of 199) had hair loss at the pin site used to secure the nurse's cap. The lesions were exclusively localized on the parieto-occipital scalp. Histopathologic findings revealed characteristic cicatricial changes which showed a marked decrease in the number of hair follicles without inflammation. CONCLUSIONS: Nurse's cap alopecia is not an uncommon occupational alopecia, and appears to be a distinct clinical entity which should be distinguished from other forms of patchy alopecia.

Adult↗

The changes of epidermal calcium gradient and transitional cells after prolonged occlusion following tape stripping in the murine epidermis.

Disruption of the epidermal permeability barrier causes an immediate loss of the calcium gradient, and barrier recovery is parallel with the restoration of the calcium gradient in the epidermis. Artificial restoration of the barrier function by occlusion with a water vapor-impermeable membrane abrogate the expected increase in lipid synthesis and retard the barrier recovery, as well as block the normalization of the epidermal calcium gradient. To clarify the long-term effects of occlusion after acute barrier perturbation, we studied the calcium distribution and epidermal keratinocytes response after occlusion with a water vapor-impermeable membrane immediately following tape stripping in the murine epidermis. Acute barrier disruption caused an immediate depletion of most calcium ions in the upper epidermis, obliterating the normal calcium gradient. When the skin barrier function was artificially corrected by occlusion, the return of calcium ions to the epidermis was blocked. After 2 h of air exposure or occlusion, the density of epidermal calcium precipitates remained negligible. The transitional cell layers appeared with occlusion, but not or negligibly with air exposure. By 6 h though, calcium precipitates could be seen, the density of the calcium precipitates with occlusion was more sparse than with air exposure. With the air exposure, the thickness of the stratum corneum had normalized and the calcium gradient nearly recovered to normal after 24 h. The longer the occlusion period, the greater was the increase of transitional cells. By 60 h of occlusion, the thickness of the stratum corneum had increased and the transitional cell layers had disappeared, in parallel with the calcium gradient which was almost normalized. These results show that prolonged occlusion of tape-stripped epidermis induced transitional cells and delayed the restoration of the epidermal calcium gradient, the stratum corneum was then restored, transitional cells having disappeared, in parallel with normalization of the epidermal calcium gradient.

Animals↗

Development and characterization of a human in vitro resorption assay: demonstration of utility using novel antiresorptive agents.

A human in vitro resorption assay has been developed using osteoclastoma-derived osteoclasts and used to evaluate novel antiresorptive agents including antagonists of the alphavbeta3 integrin, and inhibitors of cathepsin K and the osteoclast ATPase. The potency of novel compounds in the in vitro resorption assay correlates with functional assays for each class of inhibitor: the human alphavbeta3-mediated cell adhesion assay for the vitronectin receptor antagonists (r2 = 0.82), the chick osteoclast vacuolar ATPase enzyme assay for the H+-ATPase inhibitors (r2 = 0.77) and the recombinant human cathepsin K enzyme assay for the cathepsin K inhibitors (r2 = 0.80). Cell suspensions, rich in osteoclasts, are prepared by collagenase digestion of the tumor tissue. These cells can be stored long-term in liquid nitrogen and upon thawing maintain their bone-resorbing phenotype. The cryopreserved cells can be cultured on bovine cortical bone for 24-48 h and resorption can be measured by either confocal microscopy or biochemical assays. The resorptive activity of osteoclasts derived from a number of tumors can be inhibited reproducibly using a number of mechanistically unique antiresorptive compounds. In addition, the measurement of resorption pits by laser confocal microscopy correlates with the release of type I collagen C-telopeptides or N-telopeptides, as measured by enzyme-linked immunosorbent assay. Resorption can be measured reproducibly using a 48-h incubation of osteoclasts on bone slices, or a 24-h incubation with bone particles. This in vitro human osteoclast resorption assay provides a robust system for the evaluation of inhibitors of osteoclastic function that may be developed for the treatment of metabolic bone diseases such as osteoporosis.

Adenosine Triphosphatases↗

Disseminated superficial actinic porokeratosis like drug eruption: a case report.

We report a 54-year-old male patient who developed an unusual form of generalized drug eruption. He had pain and breathlessness on the left chest wall. He had history of taking several drugs at private clinics under a diagnosis of herpes zoster. Two weeks later he had a generalized skin eruption. Examination showed multiple variable sized, mild pruritic, erythematous macules and papules on the face and upper extremities. Skin lesions take the form of a clinically consistent with disseminated superficial actinic porokeratosis (DSAP). Methylprednisolone 16 mg, astemisole 10 mg, oxatomide 60 mg was prescribed. Topical corticosteroid cream was applied. Within two months, his eruption had cleared almost completely. The pathogenetic mechanisms of this case are unclear, but drug and UV light have been considered.

Drug Eruptions↗

Acne mechanica due to an orthopedic crutch.

Acne mechanica describes local irritation due to the skin being pressured, occluded, rubbed, squeezed, stretched, or heated. Examples of various physical traumas that provoke lesions in acne patients are given. Users of orthopedic crutches are at particular risk for such conditions. A crutch is another extrinsic factor to be added to the list of causes of acne mechanica.

Acneiform Eruptions↗

Design and characterization of orally active Arg-Gly-Asp peptidomimetic vitronectin receptor antagonist SB 265123 for prevention of bone loss in osteoporosis.

The Arg-Gly-Asp (RGD)-binding integrin alpha(V)beta(3) is highly expressed on osteoclasts and has been proposed to mediate cell-matrix adhesion required for osteoclast-mediated bone resorption. Antagonism of this receptor should prevent stable osteoclast adhesion and thereby inhibit bone resorption. We have generated an orally bioavailable, nonpeptide RGD mimetic alpha(v)beta(3) antagonist, SB 265123, which prevents bone loss in vivo when dosed by oral administration. SB 265123 binds alpha(v)beta(3) and the closely related integrin alpha(v)beta(5) with high affinity (K(i) = 3.5 and 1.3 nM, respectively), but binds only weakly to the related RGD-binding integrins alpha(IIb)beta(3) (K(i) >1 microM) and alpha(5)beta(1) (K(i) >1 microM). The compound inhibits alpha(v)beta(3)-mediated cell adhesion with an IC(50) = 60 nM and more importantly, inhibits human osteoclast-mediated bone resorption in vitro with an IC(50) = 48 nM. In vivo, SB 265123 completely blocks bone resorption in a thyroparathyroidectomized rat model of acute bone resorption when dosed at 2.5 mg/kg/h by continuous i.v. infusion. When dosed orally with 3 to 30 mg/kg b.i.d. , in the ovariectomy-induced rat model of osteoporosis, SB 265123 prevents bone resorption in a dose-dependent fashion. This is the first report of an orally active alpha(v)beta(3) antagonist that is effective at inhibiting bone resorption when dosed in a pharmaceutically acceptable fashion. Such a molecule may provide a novel therapeutic agent for the treatment of postmenopausal osteoporosis.

Acetates↗

The anatomy of a hypoxic operator in Saccharomyces cerevisiae.

Aerobic repression of the hypoxic genes of Saccharomyces cerevisiae is mediated by the DNA-binding protein Rox1 and the Tup1/Ssn6 general repression complex. To determine the DNA sequence requirements for repression, we carried out a mutational analysis of the consensus Rox1-binding site and an analysis of the arrangement of the Rox1 sites into operators in the hypoxic ANB1 gene. We found that single base pair substitutions in the consensus sequence resulted in lower affinities for Rox1, and the decreased affinity of Rox1 for mutant sites correlated with the ability of these sites to repress expression of the hypoxic ANB1 gene. In addition, there was a general but not complete correlation between the strength of repression of a given hypoxic gene and the compliance of the Rox1 sites in that gene to the consensus sequence. An analysis of the ANB1 operators revealed that the two Rox1 sites within an operator acted synergistically in vivo, but that Rox1 did not bind cooperatively in vitro, suggesting the presence of a higher order repression complex in the cell. In addition, the spacing or helical phasing of the Rox1 sites was not important in repression. The differential repression by the two operators of the ANB1 gene was found to be due partly to the location of the operators and partly to the sequences between the two Rox1-binding sites in each. Finally, while Rox1 repression requires the Tup1/Ssn6 general repression complex and this complex has been proposed to require the aminoterminal regions of histones H3 and H4 for full repression of a number of genes, we found that these regions were dispensable for ANB1 repression and the repression of two other hypoxic genes.

Consensus Sequence↗

Binding of [3H]-SK&F 107260 and [3H]-SB 214857 to purified integrin alphaIIbbeta3: evidence for a common binding site for cyclic arginyl-glycinyl-aspartic acid peptides and nonpeptides.

The aggregation of activated platelets is mediated by the binding of fibrinogen to its cell surface receptor, the integrin alphaIIbbeta3. The recognition of fibrinogen by alphaIIbbeta3 depends, in part, on the tripeptide sequence Arg-Gly-Asp (RGD) in the adhesive protein. The interactions of a cyclic RGD-containing pentapeptide, [3H]-SK&F-107260, and a 1,4-benzodiazepine-based nonpeptide [3H]-SB-214857, with purified alphaIIbbeta3 have been investigated. Both compounds potently inhibit platelet aggregation at submicromolar concentrations. Binding of both [3H]-SK&F-107260 (Kd = 1.19 nM) and [3H]-SB-214857 (Kd = 1.85 nM) to alphaIIbbeta3 is of high affinity and fully reversible. The binding is monophasic, indicating a single class of noncooperative binding sites. The two radioligands exhibited similar values in binding to alphaIIbbeta3 purified on an RGD-affinity column (Bmax = 0.2 mol/mol alphaIIbbeta3) or to alphaIIbbeta3 purified over a lentil lectin column (Bmax = 0.03 mol/mol alphaIIbbeta3), suggesting that SK&F-107260 and SB-214857 interact with the same population of receptors. Binding of [3H]-SK&F-107260 and [3H]-SB-214857 to alphaIIbbeta3 require divalent cations, Mg++, Ca++ and Mn++ are able to support binding, with Mn++ being the most effective. Thirteen alphaIIbbeta3 antagonists, including four linear and three cyclic RGD peptides, five peptidomimetics, the fibrinogen gamma-chain dodecapeptide (HHLGGAKQAGDV) and the snake venom protein, echistatin, complete for [3H]-SK&F-107260 or [3H]-SB-214857 binding to alphaIIbbeta3. The affinity constants (Ki) of these compounds, determined by the two radioligand binding assays, are similar. Furthermore, these compounds exhibit the same rank order of potency in inhibiting biotinylated-fibrinogen binding to alphaIIbbeta3. Scatchard plot analyses of the [3H]-SK&F-107260 binding isotherms in the presence of unlabeled SB-214857 and gamma-chain dodecapeptide reveal competitive-type antagonism, indicating that SB-214857, gamma-chain dodecapeptide and SK&F-107260 interact with mutually exclusive binding sites on alphaIIbbeta3.

Binding, Competitive↗

Cloning and characterization of a novel integrin beta3 subunit.

We have identified a novel integrin beta3 subunit, termed beta3C, from a human osteoclast cDNA library. The COOH-terminal sequence and 3'-untranslated region of the beta3C subunit differs from the previously reported beta3A (platelet) and beta3B (placenta) sequences, while the regions coding for the transmembrane and extracellular domains are identical. The beta3C cytoplasmic domain contains 37 amino acids, the last 17 of which are encoded by a novel exon located about 6 kilobase pairs downstream of exon 14 of the beta3A gene. HEK 293 cells were stably co-transfected with alphaV and either beta3C (HEKbeta3C) or beta3A (HEKbeta3A). The viability of HEKbeta3C cells was lower than that of HEKbeta3A cells, and HEKbeta3C cells in culture grew as clusters rather than as a monolayer. The novel cytoplasmic domain did not affect receptor binding affinity; both alphaVbeta3A and alphaVbeta3C isoforms exhibited high affinity binding to 125I-echistatin and cyclic and linear RGD peptides. However, in contrast to HEKbeta3A, HEKbeta3C cells failed to adhere to osteopontin, an alphaVbeta3 matrix protein. The data provide further support for the key role of the cytoplasmic domain of the beta3 integrin in cell adhesion and suggest a potential role for the beta3C integrin subunit in modulating cell-matrix interactions.

Amino Acid Sequence↗

Nevus spilus (speckled lentiginous nevus) associated with a nodular neurotized nevus.

We report a case of nevus spilus with neurotized nevus studied by immunohistochemical methods using S-100, leu-6, glial fibrillary acid protein (GFAP), and myelin basic protein (MBP). Histologic findings of the speckled lesion showed irregular rete ridge elongation, increased epidermal melanocytes and melanin in the epidermis, and scattered nevus cell nests in the upper dermis, but showed neurotized nevus in the deep dermis, which has many features of neurofibroma. Diffuse expression of S-100 protein and MBP, focal staining with GFAP, and lack of staining with leu-7 were observed, Leu-7, positive only in neurofibromas and not in neurotized nevus, appears to be the more pertinent method for distinguishing neurotized nevus from neurofibroma.

CD57 Antigens↗