TWEAK inhibits TGF-beta-induced contraction of normal and keloid fibroblast-embedded collagen gel.
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Cells, Cultured↗
Biomedical subjects
Toshio Hasegawa
Publications and source records attributed to Toshio Hasegawa.
Challenge to detect 1,4-zwitterions spectroscopically in a ketene-alkene reaction.
The first example of direct spectroscopic detection of transient species, 1,4-zwitterions, generated in a ketene-alkene reaction is reported. Also, a striking result of the intervention of an unprecedented "1,4-zwitterion neutral dimer" is presented in a new mechanistic pathway; the ketene-alkene reaction gives the product cyclobutanone from the initial cycloadduct alpha-methyleneoxetane.
Journal Article↗
A case of peeling skin syndrome successfully treated with topical calcipotriol.
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Administration, Cutaneous↗
Clinical trial of a laser device called fractional photothermolysis system for acne scars.
Ablative laser resurfacing is an effective treatment for acne scars. However, edema and prolonged erythema are common. Additionally, scarring and hyperpigmentation are often induced. A new concept of laser called fractional photothermolysis has been designed to create microscopic thermal wounds to achieve skin rejuvenation without significant side-effects. We treated 10 patients with acne scars using this laser system (Reliant Fraxel SR Laser). All the patients were successfully treated with minimal adverse effects. The fractional photothermolysis system represents an optional method for the treatment of acne scars.
Acne Vulgaris↗
Psoriasiform and palmoplanter pustular lesions induced after Kawasaki disease.
A 7-month-old boy was referred to us because of psoriatic lesions on the bilateral cheeks and on the extensor region of the left upper arm at the same site of his vaccination for tuberculosis 4 months previously (Fig. 1a,b). He also presented with small pustules scattered on the palms and soles (Fig. 1c).
Epidermis↗
SB-431542 inhibits TGF-beta-induced contraction of collagen gel by normal and keloid fibroblasts.
BACKGROUND: Transforming growth factor (TGF)-beta induces fibroblast contraction, which is implicated in wound healing and keloid formation. SB-431542 is a novel specific inhibitor of TGF-beta type I receptor kinase activity. OBJECTIVE: We sought to determine whether SB-431542 inhibited TGF-beta-induced fibroblast contraction. METHODS: We used an in vitro type I collagen gel contraction assay with normal or keloid dermal fibroblasts incorporated. RESULTS: TGF-beta induced contraction of collagen gels with normal dermal fibroblasts incorporated, which was efficiently suppressed by SB-431542. Keloid fibroblasts showed higher basal contraction of collagen gels in the absence of TGF-beta than normal fibroblasts, which was enhanced by addition of TGF-beta. SB-431542 suppressed both the basal and TGF-beta-enhanced contraction of collagen gels by keloid fibroblasts. These inhibitory effects of SB-431542 were associated with suppression of TGF-beta-induced alpha-smooth muscle actin (alpha-SMA) expression and phosphorylation of Smad2 in normal and keloid fibroblasts. CONCLUSION: SB-431542 can suppress TGF-beta-induced contraction of collagen gel by normal and keloid dermal fibroblasts. Importantly, SB-431542 can inhibit basal contraction of collagen gel by keloid fibroblasts. These results suggest that an inhibitor of TGF-beta type I receptor kinase activity may have therapeutic potential for excessive skin contraction as observed in keloid.
Actins↗
Bisabolane- and santalane-type sesquiterpenoids from Santalum album of Indian origin.
Six new bisabolane-type (1-3) and santalane-type (4-6) sesquiterpenoids, together with (+)-alpha-nuciferol, (+)-citronellol, and geraniol, were isolated from the heartwood of Santalum album of Indian origin. Their structures, including two bisabolol diastereomers (1, 2), were established on the basis of spectroscopic data interpretation.
Acyclic Monoterpenes↗
An allogeneic cultured dermal substitute suitable for treating intractable skin ulcers and large skin defects prior to autologous skin grafting: three case reports.
Intractable skin ulcers that arise as secondary lesions from disease and full-thickness skin defects that result from skin tumor excision often need autologous skin grafting to close the wound. We developed an allogeneic cultured dermal substitute (CDS) to shorten the time needed to prepare a wound bed suitable for autologous skin grafting. The CDS was prepared by plating normal human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelo-collagen. The allogeneic CDS was then placed on the rinsed wound surface. This procedure was repeated twice a week for up to five weeks, until the wounds were closed by autologous skin grafting. In all three cases, after CDS treatment for two to five weeks, the wound conditions became suitable for skin grafting; these conditions had not been improved by conventional topical treatments, including topical basic fibroblast growth factor (bFGF). Healthy granulation tissue developed rapidly, concomitant with wound size reduction. The present results indicate that CDS is an excellent biological wound dressing for improving wound conditions so that they are suitable for subsequent autologous skin grafting as well as for shortening the treatment duration for skin ulcers and full-thickness skin defects.
Aged↗
Aromatic constituents from the heartwood of Santalum album L.
A phytochemical investigation of the polar constituents in the heartwood of Indian Santalum album L. resulted in the isolation of three new neolignans (1-3) and a new aromatic ester (4), along with 14 known components. The structures of the new compounds (1-4) were established using spectroscopic methods.
Lignans↗
Differentiation-specific localization of catalase and hydrogen peroxide, and their alterations in rat skin exposed to ultraviolet B rays.
BACKGROUND: It is now well known that to counteract oxidative stress and maintain a redox balance within the cells, the skin is equipped with a network of antioxidant enzymes. Among these enzymes, SOD and CAT are the major antioxidant enzymes protecting the epidermis. OBJECTIVE: In the present study, we have attempted to demonstrate the distribution of endogenous H(2)O(2) and the expression of CAT in the epidermis of newborn rats, in relation to epidermal differentiation, and alterations after UVB irradiation. METHODS: We have localized the antioxidant enzyme catalase (CAT) using immunohistochemical analysis, and hydrogen peroxide (H(2)O(2)) using in situ H(2)O(2) assay. RESULTS: We demonstrated that keratinocytes in the stratum granulosum produced H(2)O(2), and CAT was mainly expressed in the cytoplasm of cells from the stratum granulosum to the lower corneum, and in the cell periphery in the stratum granulosum of newborn rat skin. The results suggested that generation of H(2)O(2) and expression of CAT were coordinated and were indicative of epidermal differentiation as well as of the role of CAT in repairing redox damage by discomposing H(2)O(2). When rat skin was exposed to 50 mJ/cm(2) of ultraviolet B (UVB) rays, the accumulation of H(2)O(2) in the upper epidermis increased twenty-four hours later, while CAT immunoreactivity decreased. CONCLUSION: The results suggested that generation of H(2)O(2) and expression of CAT were coordinated and were indicative of epidermal differentiation as well as of the role of CAT in repairing redox damage by discomposing H(2)O(2). In addition, UVB-induced oxidative stress in the present study seemed to alter the endogenous and differentiation-specific redox balance between H(2)O(2) and CAT.
Animals↗
Antioxidant capacities of ascorbic acid, uric acid, alpha-tocopherol, and bilirubin can be measured in the presence of another antioxidant, serum albumin.
Human serum contains several antioxidants. The total antioxidant capacity (AOC) is the sum of all the antioxidant activities present in serum. The aim of our study was to investigate whether the AOC of bilirubin (BR), alpha-tocopherol (TOH), ascorbic acid (AA), and uric acid (UA) could be measured with good precision and recovery in the presence of human serum albumin (HSA). We measured the AOC of each antioxidant using a Cobas Mira S instrument (Roche Diagnostic Systems, Montclair, NJ) by measuring the inhibitory effect of a given compound on the oxidation of the radical cations of 2,2'-azino-di-(3-ethylbenzthiazoline 6-sulphonate) (ABTS) incubated with metmyoglobin and H(2)O(2). The assay had a linear AOC response range of 27-2,000 micromol/L. The within- and between-day coefficients of variation (CVs) did not exceed 3.4% and 4.2%, respectively. The AOC of albumin in serum is much greater than that of BR, TOH, AA, or UA owing to the substantially greater concentration of HSA in serum. An aliquot of a solution of AA, UA, BR, or TOH was added to HSA or distilled water, and the AOC was determined. The AOC of BR, TOH, AA, and UA increased in a linear way with increasing concentrations. However, we found that the magnitude of increase in the AOC of a mixture of HSA and any of these antioxidants was lower than the sum of the AOC of HSA and any one of the following: AA, UA, BR, or TOH (all expressed in micromol/L).
Antioxidants↗
Clinical trial of allogeneic cultured dermal substitute for the treatment of intractable skin ulcers in 3 patients with recessive dystrophic epidermolysis bullosa.
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Cells, Cultured↗
Oxidative stress is enhanced in correlation with renal dysfunction: examination with the redox state of albumin.
BACKGROUND: Cardiovascular disease is known to be the most important complication among patients with renal failure, and oxidative stress has been proposed to play a major role as the source of such complications. Human serum albumin (HSA) is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing powers, of reversibly oxidized human non-mercaptoalbumin-1 (HNA-1), and strongly oxidized human non-mercaptoalbumin-2 (HNA-2). METHODS: We used the "redox state of HSA" as a marker to investigate the current status of oxidative stress in predialysis patients with renal failure. The subjects were 55 nondialysis patients (31 males and 24 females) with chronic renal diseases, and having various degrees of renal function. The subjects' redox state of HSA was determined by a high-performance liquid chromatographic (HPLC) procedure, and the results presented in terms of the ratios between HNA-total(HNA-1 + HNA-2) and HNA-2. RESULTS: The values for each fraction of HNA-total (f(HNA-total)) and f(HNA-2) were increased with a decrease of renal functions, and a significant positive correlation with serum creatinine (R= 0.529, P < 0.0001 and R= 0.618, P < 0.0001) was detected. Multiple (forward stepwise) regression analysis using f(HNA-total) and f(HNA-2) as the criterion variables was performed, and creatinine was adopted as significant explanatory variable in both equations. CONCLUSION: We found that even before dialysis, oxidative stress was enhanced in correlation with the level of renal dysfunction among patients with chronic renal failure. In the future, antioxidant strategies should become part of treatment for predialysis renal failure.
Adult↗
Measurement of translymphatic fluid absorption using technetium-99m human serum albumin diethylenetriamine pentaacetic acid in continuous ambulatory peritoneal dialysis patients.
We have established a new method of measuring translymphatic fluid absorption (TLA) using technetium-99m ((99m)Tc) human serum albumin diethylenetriamine pentaacetic acid ((99m)Tc-HSAD) that can be used commonly in clinical practice. This new method was applied in 13 continuous ambulatory peritoneal dialysis patients (11 males and two females) who had various peritoneal permeability and capacities for peritoneal transport of water. (99m)Tc-HSAD 740MBq was injected in 2 L of peritoneal dialysis fluid with 2.5% glucose, mixed well, and administered intraperitoneally. The fluid was drained extraperitoneally after 4 h and TLA was determined by the in vivo loss of (99m)Tc-HSAD. TLA was 1.41 +/- 1.11 mL/min (mean +/- SD; range, 0.27-3.69 mL/min). The estimated reduction rate by TLA in trans-peritoneally removed fluid ranged from 14.2 to 84.4%, indicating that TLA could have an extremely significant negative effect in some cases on total drainage volume. The present study, using new tracer (99m)Tc-HSAD, could confirm a large individual difference in TLA, indicating TLA as an important contributing factor for fluid-removal failure in continuous ambulatory peritoneal dialysis patients.
Absorption↗
Exclusive formation of alpha-methyleneoxetanes in ketene-alkene cycloadditions. Evidence for intervention of both an alpha-methyleneoxetane and the subsequent 1,4-zwitterion.
This paper describes a new mechanistic feature for the Staudinger ketene-alkene cycloaddition reactions to give cyclobutanones. Low-temperature NMR (13C, 19F, and 1H) monitoring of a reaction between bis(trifluoromethyl)ketene (1) and ethyl vinyl ether (2) has shown that the Staudinger reaction proceeds to form initially and exclusively an alpha-methyleneoxetane (3) by [2 + 2](C=O) cycloaddition across the ketene C=O bond. The initial intermediate 3 undergoes ring cleavage to produce a 1,4-zwitterion (4), which is converted to the final [2 + 2](C=C)-type product, cyclobutanone (5). The key intermediate 3 has been isolated in its pure form and was found to be converted to the final products 5 on warming, via the 1,4-zwitterion 4. The alpha-methyleneoxetane 3 is so reactive that it reacts with methanol rapidly even at -80 degrees C via solvolysis to afford an adduct 7. The ion 4 derived from the pure isolated oxetane 3 was intercepted with acetone by a 1,4-dipolar cycloaddition to give a 1,3-dioxane 8. An open-chain alpha,beta-enone (6) has been also obtained from 3. We conclude that the (1 + 2) reaction proceeds in a new three-step mechanism; formation of an alpha-methyleneoxetane 3, a [2 + 2]-type cycloadduct across the C=O bond of ketene, followed by ring cleavage to give the zwitterion 4 and by recombination to form the final product, cyclobutanone 5. The zwitterion 4 is not equilibrating with reactants 1 and 2 but comes from the alpha-methyleneoxetane 3. Exclusive formation of another oxetane 12 has been observed in a reaction between diphenylketene (9) and methyl isopropenyl ether (11). The selectivity of initial formation of cyclobutanone or oxetane has been generalized with aid of frontier-orbital theory and ab initio calculations.
Journal Article↗
IFN-gamma fails to antagonize fibrotic effect of TGF-beta on keloid-derived dermal fibroblasts.
BACKGROUND: Interferon-gamma (IFN-gamma) has been noted as a potential therapeutic agent for various fibrotic disorders, in part, through its antagonistic effect on a fibrogenic cytokine, transforming growth factor-beta (TGF-beta). Keloid is a fibrotic skin disorder that results in an excessive deposition of extracellular matrix, which is associated with altered-expression of or -responses to TGF-beta in dermal fibroblasts. OBJECTIVE: We sought to determine whether IFN-gamma antagonized TGF-beta-mediated fibrotic response in keloid-derived dermal fibroblasts. METHODS: Type I collagen production, fibroblast contractile activity, and alpha-smooth muscle actin (alpha-SMA) expression were assessed by using Western blotting, an in vitro type I collagen gel contraction assay, and immunofluorescence study in normal and keloid-derived human dermal fibroblasts in the presence or absence of IFN-gamma and/or TGF-beta. RESULTS: In contrast to normal dermal fibroblasts, IFN-gamma did not inhibit TGF-beta-induced type I collagen production, contractile activity, and alpha-SMA expression in keloid-derived dermal fibroblasts. In addition, keloid-derived dermal fibroblasts constitutively expressed type I collagen and alpha-SMA with increased capacity to contract a collagen matrix. CONCLUSION: IFN-gamma failed to antagonize TGF-beta-mediated fibrotic response in keloid-derived dermal fibroblasts. Thus, IFN-gamma may not be therapeutically useful for keloid and clarification of the molecular mechanisms underlying the IFN-gamma resistance should be investigated for therapeutic application of IFN-gamma for keloid.
Actins↗
[A case of allopurinol-induced muscular damage in a chronic renal failure patient].
A 73-year-old woman with chronic renal failure developed generalized muscular weakness and pain 6 days after the start of allopurinol treatment(200 mg/day). Routine laboratory tests revealed elevated levels of serum creatine kinase, and the patient was clinically diagnosed as rhabdomyolysis, due probably to severe myositis. A high level of serum oxipurinol, the chief active metabolite of allopurinol, was also revealed. The muscular weakness was relieved in seven weeks with intermittent hemodiafiltration.
Aged↗
High-transport membrane is a risk factor for encapsulating peritoneal sclerosis developing after long-term continuous ambulatory peritoneal dialysis treatment.
Increased peritoneal function has been suggested to be a risk factor for developing encapsulating peritoneal sclerosis (EPS); however, clinical evidence is scarce. The present study aimed to clarify the specific character of peritoneal function in patients who developed EPS after withdrawal from peritoneal dialysis (PD). We studied 12 patients who developed EPS after PD withdrawal [(EPS group) mean PD duration: 109 months; mean period of EPS development: 7.0 months after withdrawal] and 128 patients who did not develop EPS (non EPS group). All 140 patients were withdrawn from continuous ambulatory peritoneal dialysis (CAPD) and were observed for the following 24 months. Based on the records of the annual peritoneal equilibration tests (PETs), we analyzed (1) the patients' dialysate-to-plasma (D/P) creatinine at various durations on PD, and (2) the accumulative appearance incidence of high-transport (HT) state of peritoneal membrane. The mean D/P creatinine in EPS group was significantly higher than that in the non EPS group in the course of PD from the 6th to the 10th year. The accumulative incidence of HT was significantly higher in the EPS group than in the non EPS group, indicating early development of HT membrane in EPS group. Early development of increased D/P creatinine, classified as HT state, was observed during certain periods on PD in patients who developed EPS after PD withdrawal. That finding may indicate that HT state of peritoneal membrane is an early marker for EPS, and that the PET is useful to detect patients at high risk of EPS.
Adult↗