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Biomedical subjects

M Kawashima

Publications and source records attributed to M Kawashima.

At least 37 records · Page 2Linked to original sources
PubMed2003

Addition of fexofenadine to a topical corticosteroid reduces the pruritus associated with atopic dermatitis in a 1-week randomized, multicentre, double-blind, placebo-controlled, parallel-group study.

BACKGROUND: Fexofenadine, a nonsedating, H1-receptor selective antihistamine, exhibits consistent efficacy and safety in the treatment of allergic rhinitis and urticaria. The pruritus associated with atopic dermatitis is considered to be induced, in part, by histamine. Therefore, we thought that fexofenadine may be useful in the relief of pruritus associated with atopic dermatitis. OBJECTIVE: To compare the efficacy of twice-daily fexofenadine hydrochloride (HCl) 60 mg vs. placebo in reducing the pruritus associated with atopic dermatitis. METHODS: In this randomized, multicentre, double-blind, placebo-controlled study, patients (aged >or= 16 years) with atopic dermatitis underwent a 1-week placebo lead-in period, followed by randomization to fexofenadine HCl 60 mg twice daily or placebo for 1 week. All patients also received topical treatment with 0.1% hydrocortisone butyrate twice daily throughout the study. The primary efficacy endpoint was mean change in pruritus score from baseline. Patients reflectively recorded pruritus scores twice daily (day and night) using a five-point scale (0 = none; 4 = very severe). RESULTS: Fexofenadine (n = 201) significantly decreased the severity of pruritus compared with placebo (n = 199) (mean change in score -0.75 (unadjusted 95% confidence interval [-0.88, -0.62]) vs. -0.5 [-0.62, -0.38], respectively; P = 0.0005). This improvement was seen after just 1 day of treatment (P = 0.039) and was maintained throughout the treatment period (P = 0.019). Compared with placebo, fexofenadine significantly improved both diurnal (P = 0.0001) and nocturnal pruritus (P = 0.013). In addition, significantly more patients in the fexofenadine group experienced a reduction in the ratio of pruritus area to body surface area compared with those in the placebo group (P = 0.007). The incidence of adverse events was low and similar across all treatment groups. CONCLUSIONS: Fexofenadine HCl 60 mg twice daily demonstrated a rapid, significant improvement in the pruritus associated with atopic dermatitis, with a safety profile equivalent to that of placebo.

Adolescent↗
PubMed2003

Arginine vasotocin induces bearing down for oviposition in the hen.

An intravenous injection of arginine vasotocin (AVT) at 16 h before the expected oviposition of the initial egg of an egg-laying sequence caused bearing down for oviposition. Oviposition was increased up to 100% by increasing the dose of AVT up to 1 microg, but it decreased when the dose was 10 and 20 microg. Bearing down was observed even when the oviposition was not induced by the injection of a higher dose of AVT. The results of the present experiment suggest that bearing down is not necessarily caused by the entering of egg into the vagina, but instead may be caused by hormonal stimulus of AVT receptors present in vaginal tissue.

Animals↗
PubMed2002

Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced acute lung injury.

14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases. This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM). Their effects were compared with macrolide untreated, pretreated, and post-treated groups. An acute lung injury was inhibited by pretreatment with CAM or RXM, which significantly ameliorated the bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluids and the wet lung weight. The pretreatment with CAM or RXM also suppressed inflammatory cell infiltration and interstitial lung edema in the histopathological study. These inhibitory effects were associated with a decreased KC concentration in the BAL fluid and a decreased number of apoptotic cells in the lungs. Posttreatment with CAM or RXM had no marked inhibitory effects. Pretreatment with AZM was much less effective, and JM showed no inhibitory effects. These findings suggest that 14-membered ring macrolides have different effects on inflammatory lung disease than 15- and 16-membered ring macrolides and may be therapeutic agents for acute lung injury and pulmonary fibrosis.

Animals↗
PubMed2002

Antileukinate, a hexapeptide inhibitor of CXC-chemokine receptor, suppresses bleomycin-induced acute lung injury in mice.

A hexapeptide, Ac-RRWWCR-NH(2) (Antileukinate), has been reported to be a potent inhibitor of CXC-chemokine receptor. However, the in vivo anti-inflammatory activity of this agent has not been tested except in a rabbit skin edema model. This study was undertaken to investigate the effect of subcutaneously administered Antileukinate on experimental bleomycin-induced acute lung injury in mice, in which CXC-chemokines have been reported to be involved. Lung injury was assessed on the basis of histopathology, the number of total cells, the percentage of neutrophils, and protein concentration in the bronchoalveolar lavage (BAL) fluid, and the wet lung weight at 7 days after intratracheal instillation of bleomycin. Histopathological studies revealed that treatment with Antileukinate markedly suppressed inflammatory cell infiltration and interstitial lung edema. The neutrophil counts in the BAL fluid were significantly decreased in the Antileukinate-treated group. The suppression of pulmonary edema was further confirmed by the reduction of wet lung weight and total protein concentration in the BAL fluid. These findings suggest that Antileukinate is able to inhibit acute lung injury by suppressing neutrophil mobilization induced by CXC-chemokines.

Animals↗
PubMed2002

Atopic dermatitis management: comparing the treatment patterns of dermatologists in Japan, U.S.A. and U.K.

BACKGROUND: The incidence of atopic dermatitis (AD) is increasing worldwide. No large-scale study has previously compared the therapeutic management of this condition in different countries. OBJECTIVES: The purpose of this study was to determine the treatment preferences of dermatologists in Japan, the U.S.A. and the U.K., and investigate their relationship with certain factors pertaining to the physician and his practice. METHODS: A questionnaire was sent to all registered members of dermatological societies in Japan, the U.S.A. and the U.K. Responses were collated and statistical analysis performed using chi2, Mantel-Haenszel and Breslow heterogeneity tests. RESULTS: Three thousand six hundred and eighty-eight completed surveys were returned. U.S.A. and U.K. physicians were significantly more aggressive in prescribing systemic medications, such as steroids, antibiotics and immunosuppressants, compared with those in Japan. Japanese dermatologists also utilized topical steroids significantly less. The use of alternative remedies was highest in Japan. All three countries had a relatively high degree of optimism for topical immunosuppressants, but less so for other emerging therapies. CONCLUSIONS: Both similarities and differences in the therapy of AD exist in the three countries studied. Factors related to the physician, patient population and culture may influence these observations.

Adult↗
PubMed2002

A novel sialyl Lewis(x) analogue attenuates ischemia reperfusion injury in rabbit lung.

BACKGROUND: We investigated the effects of OJ-R9545, a novel Sialyl Lewis x analogue, on lung ischemia-reperfusion (IR) injury using an in vivo rabbit model. METHODS: The left hilum of the lung was clamped for 110 minutes; the lung was then reperfused for 90 minutes. Either OJ-R9545 (10 mg/kg) or vehicle solution was administered from 10 minutes before reperfusion to 60 minutes after reperfusion in the OJ-R (+) and OJ-R (-) group (n = 6 in each group), respectively. The sham group (n = 3) underwent an identical procedure without ischemia. RESULTS: Arterial oxygen tensions in the OJ-R (+) group were superior to those in the OJ-R (-) group from 30 to 90 minutes after reperfusion (p < 0.05 and p < 0.01). Lung wet/dry weight ratio and myeloperoxidase activity after reperfusion in the OJ-R (+) group were both significantly lower than the corresponding figures in the OJ-R (-) group (p < 0.05). The intrapulmonary leukocytes were significantly reduced in the OJ-R (+) group compared with those in the OJ-R (-) group (p < 0.01). CONCLUSIONS: OJ-R9545 attenuates lung IR injury by preventing leukocyte infiltration into the lung.

Animals↗
PubMed2001

Interferon-gamma-inducing activity of interleukin-18 in the joint with rheumatoid arthritis.

OBJECTIVE: To examine the levels of interleukin-18 (IL-18) bioactivity within the rheumatoid arthritis (RA) joint, and the differential effects of IL-12 and IL-18 on interferon-gamma (IFNgamma) production by T cell infiltrates. METHODS: Expression of IL-18 protein and messenger RNA (mRNA) was determined by enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction, respectively. The biologic activity of IL-18 was detected on the basis of IFNgamma secretion from IL-18-responding human myelomonocytic KG-1 cells. To determine the extent of inhibitory activity on binding of IL-18 to its receptor, a [125I]-IL-18 binding inhibition assay was performed, using a Chinese hamster ovary cell line transfected with a murine IL-18 receptor. RESULTS: The amount of IL-18 protein detected in both the serum and synovial fluid of RA patients was markedly larger than that detected in the serum and synovial fluid ofosteoarthritis (OA) patients, and serum IL-18 levels correlated with the levels of serum C-reactive protein. IFNgamma production by KG-1 cells was more strongly stimulated in synovial fluid samples from RA patients than in samples from OA patients, and this activity was largely diminished in the presence of anti-IL-18 antibody. In contrast, the activity of IL-18 binding inhibition in the serum and synovial fluid of RA patients was not significantly elevated compared with that in OA patients. RA synovial tissues showed increased expression of IL-18 mRNA and increased IL-18 protein synthesis compared with that in OA tissues. Purified CD14+ macrophages, but not activated fibroblast cell lines, from RA synovium were able to release mature IL-18, although both cell types expressed its transcripts. IL-18 alone showed a negligible effect on IFNgamma production by RA synovial tissue cells, in contrast to IL-12, which was directly stimulatory. However, IL-12-induced IFNgamma production was synergistically enhanced by IL-18, and yet was >50% reduced by neutralization of endogenous IL-18 with anti-IL-18 antibody. CONCLUSION: These results indicate that IL-18, produced predominantly by tissue macrophages, primarily potentiates IL-12-induced IFNgamma production by T cell infiltrates in RA synovium. Detection of significant IL-18 bioactivity in the joints, despite the presence of IL-18 binding inhibitors, supports an integral role of this cytokine in perpetuating the IFNgamma-dominant T cell cytokine response in RA.

Antibody Formation↗
PubMed2001

Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients with adult-onset Still's disease.

OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine that is involved in immunologically mediated tissue damage, but its bioactivity is regulated in vivo by its soluble decoy receptor, IL-18 binding protein (IL-18BP). This study was undertaken to determine levels of IL-18 and IL-18 binding inhibition in the blood of patients with adult-onset Still's disease (ASD). METHODS: Serum concentrations of IL-18 in ASD patients were compared by enzyme-linked immunosorbent assay (ELISA) with those in patients with other systemic rheumatic diseases and healthy controls. The biologically active mature protein of IL-18 was detected by Western blot analysis with anti-IL-18 antibody and its induction of interferon-gamma (IFNgamma) secretion from IL-18-responding human myelomonocytic KG-1 cells. The inhibitory activity on IL-18 binding to its receptor was determined by 125I-IL-18 binding inhibition assay using the Chinese hamster ovary cell line transfected with a murine IL-18 receptor (CHO-K1/mIL-18R). RESULTS: Concentrations of serum IL-18 were extremely elevated in patients with active ASD compared with those in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, Sjogren's syndrome, or healthy individuals. Levels of IL-18 were found to correlate with serum ferritin values and disease severity in ASD. Western blot analysis revealed that serum samples from patients with active ASD contained an 18-kd polypeptide of IL-18, corresponding in size to the mature form. Accordingly, the samples were able to induce IFNgamma secretion from KG-1 cells, which was largely abolished by neutralizing anti-IL-18 antibody. However, the level of IL-18 bioactivity was more than 10-fold weaker than the concentration of IL-18 protein measured by ELISA. Serum samples from patients with active ASD showed an inhibitory effect on the binding of 125I-IL-18 to CHO-K1/mIL-18R cells, and this activity was associated with elevation of IL-18. CONCLUSION: These data indicate that systemic overproduction of IL-18 may be closely related to the pathogenesis of ASD, despite the restriction on its inflammatory activity by IL-18 binding inhibitors such as IL-18BP. The disease activity appears to be determined on the basis of the relative levels of IL-18 and its specific inhibitors.

Adult↗
PubMed2001

A novel selectin blocker alleviates oxidative stress of lung reperfusion injury.

BACKGROUND: The importance of reactive oxygen species released through interaction of leukocyte/endothelial cell in ischemia-reperfusion injury of the lung is not yet fully understood. A novel selectin blocker, OJ-R9188, which inhibits the interaction, may alleviate oxidative stress and pulmonary dysfunction after warm ischemia-reperfusion. MATERIALS AND METHODS: Rat lungs were reperfused at 37 degrees C for 60 min with an ex vivo model and were divided into three groups (n = 10). In the fresh group, lungs were reperfused immediately after harvest. In the OJ-R (-) and OJ-R (+) groups, lungs were reperfused after warm ischemia at 37 degrees C for 90 min. In the OJ-R (+) group, rats received 100 microg per body of OJ-R9188 intravenously 10 min before the harvest. The electron spin resonance method was used to assess the direct scavenging activity of OJ-R9188. RESULTS: Both shunt fractions and wet/dry weight ratios of the lung tissue after reperfusion in the OJ-R (+) group were significantly lower than those in the OJ-R (-) group. Oxidative DNA damage in the alveolar wall of the OJ-R (+) group, assessed by immunohistochemical quantitation of 8-hydroxy-2'-deoxyguanosine, was significantly lower than that of the OJ-R (-) group. Immunostaining of 3-nitro-l-tyrosine, which represents nitric oxide-mediated oxidative damage, was also more intense in the OJ-R (-) group than in the OJ-R (+) group. Direct scavenging activity of OJ-R9188 was not observed, and the number of leukocytes infiltrated to the lung tissue as seen by myeloperoxidase activity was not different between the OJ-R (-) and OJ-R (+) groups. CONCLUSIONS: A novel selectin blocker, OJ-R9188, improves pulmonary function after warm ischemia-reperfusion and alleviates reperfusion-induced oxidative alveolar damage.

Animals↗
PubMed2001

Different responses of benign and atypical meningiomas to gamma-knife radiosurgery: report of two cases with immunohistochemical analysis.

Recent reports have shown that gamma-knife radiosurgery provides a safe and effective strategy for the management of brain tumors. To evaluate the role of stereotactic radiosurgery in the management of meningiomas, we investigated the histopathology of two patients. The patients, a 37-year-old man and a 54-year-old woman, presented with visual field disturbance or headache. Imaging studies demonstrated intracranial meningiomas--tentorial and sphenoid ridge, respectively. Each patient undewent subtotal surgical resection (more than 90% in both patients), followed by gamma-knife radiosurgery of the remnant tumor marginal doses of 15 Gy. Pathological examination of the original tumors revealed a meningothelial meningioma and an atypical meningioma, respectively. Enlargement of the remnant tumors 4 months after radiosurgery resulted in total surgical resection in both patients. Thirteen months later, the patient with the atypical meningioma underwent a third operation for early recurrence of the tumor. Histopathology was investigated, and MIB-1, p53, and bcl-2 labeling indexes (LI) were analyzed immunohistochemically. Histopathologically, the specimens showed necrosis and intratumoral vessel obliteration after radiosurgery in both cases. However, more remnant tumor cells survived in the atypical meningioma. Immunohistochemically, increased wild-type p53, decreased bcl-2 expression, and decreased MIB-1 LI were observed in the benign meningioma. In the atypical meningioma, on the contrary, MIB-1 LI was decreased and mutant-type p53 and bcl-2 expression were unchanged. The specimen from the third operation revealed an anaplastic meningioma, and MIB-1 LI was markedly increased. These findings suggest that the efficacy of radiosurgery may differ between benign and atypical meningiomas.

Adult↗
PubMed2001

Accumulation of 67Ga citrate in early pregnancy.

A 26-year-old pregnant woman complained of chest pain and dyspnea and was diagnosed with malignant lymphoma of the mediastinum. To determine the stage of malignant lymphoma, tumor scintigraphy with 67Ga citrate was performed. 67Ga scintigraphy revealed an abnormal accumulation in the center of the pelvic cavity. An artificial abortion was performed, and the early pregnancy obtained from the abortion showed a prominent uptake of 67Ga citrate ex vivo. 67Ga citrate re-examination, which was performed immediately after the abortion, showed no abnormal accumulation in the pelvic cavity. To our knowledge, this is the first medical report on an aborted tissue investigated ex vivo to determine whether it demonstrated increased uptake of 67Ga citrate.

Abortion, Induced↗
PubMed2001

Auditory threshold reduction on alcohol ingestion.

RATIONALE: Auditory threshold (AT) measurement method has become the standard behavioral procedure for describing auditory sensitivity. Therefore, the AT measurement method is applicable to evaluation of auditory function. However, only a few studies have been performed to clarify the alteration of audibility under the influence of alcohol on normal humans by measurement of AT. OBJECTIVE: The fact that blood alcohol concentration (BAC) is influenced by the dose of alcohol and the time of measurement suggests that the effects of alcohol may also be altered by the same factors. The present study was conducted to elucidate how alcohol ingestion method affects the AT at a wider range from lower to higher frequency in the time course. METHODS: Fifteen paid Japanese (seven men and eight women, 20-33 years of age) were employed in AT measurements at an octave frequency ranging from 250 to 8,000 Hz before and 5, 30, 60, 120, 240 and 480 min after drinking various amounts (125, 250, 500 and 1,500 ml) of normal beer (5% alcohol) or alcohol-free beer. RESULTS: The AT was significantly reduced within 30 min after the ingestion of 250 and 500 ml of beer, occurring on and after peak BAC. The reducing effect disappeared 480 min after ingestion. CONCLUSIONS: Drinking extra small amounts of alcohol induces the reduction of AT. The effect of alcohol on AT is altered by the alcoholic dose used in testing.

Adult↗
PubMed2001

Differential in vitro effects of IL-4, IL-10, and IL-13 on proinflammatory cytokine production and fibroblast proliferation in rheumatoid synovium.

The purpose of this study was to compare the potential of interleukin-4 (IL-4), IL-10, and IL-13 to interrupt two major inflammatory pathways in rheumatoid arthritis (RA), i.e., overexpression of proinflammatory cytokines and cytokine-mediated fibroblast growth. IL-4, IL-10, and IL-13 were all able to significantly inhibit the production of IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 by freshly isolated RA synovial tissue cells, IL-10 was most effective in terms of IL-1beta and TNF-alpha reduction. The IL-1 receptor antagonist was enhanced by IL-4 and IL-13, but only slightly enhanced by IL-10. Spontaneous interferon-gamma secretion was diminished by IL-4 and IL-10 but not by IL-13. Addition of anti-IL-10 neutralizing antibody to RA synovial tissue cells resulted in a substantial increase in IL-1beta and TNF-alpha levels, whereas neither anti-IL-4 nor anti-IL-13 antibody had a significant effect. IL-1beta-stimulated proliferation of RA synovial fibroblast cell lines was inhibited by IL-4 and IL-13, but not by IL-10; IL-4 was over tenfold more effective than IL-13. These results suggest that IL-4, IL-10, and IL-13 all have the therapeutic potential to regulate the disease activity mediated by proinflammatory cytokines in RA, but each cytokine may have different potencies.

Arthritis, Rheumatoid↗
PubMed2001

Case-control study with narcoleptic patients and healthy controls who, like the patients, possess both HLA-DRB1*1501 and -DQB1*0602.

In previous studies, we suggested that the tumor necrosis factor (TNF-alpha and its receptor 2 (TNFR2) genes could be associated with the susceptibility to human narcolepsy, and that haplotype carrying DRB1*1502 had a negative association with the disorder. To further evaluate these associations, we herein compared narcoleptic patients with healthy individuals who, like the patients, possessed both DRB1*1501 and DQB1*0602. Results agreed with the negative association of DRB1*1502 and positive association of the TNF-alpha(-857T) and TNFR2-196R combination with the disorder. In addition, a significant association of the TNF-alpha(-857T) homozygote with the disorder and an increase in a rare haplotype carrying DRB1*1501 and TNF-alpha(-857T) in the patients were also observed in the present study.

Alleles↗
PubMed2001

Prostaglandin D synthase (beta-trace) in meningeal hemangiopericytoma.

The level of prostaglandin D synthase (PGDS), a major protein constituent of cerebrospinal fluid (CSF), is altered in various brain diseases, including meningitis. However, its role in the brain remains unclear. PGDS is mainly synthesized in the arachnoid cells, the choroid plexus and oligodendrocytes in the central nervous system. Among brain tumors, meningiomas showed intense immunoreactivity to PGDS in the perinuclear region. Thus, PGDS has been considered a specific cell marker of meningioma. In this study, we examined 25 meningeal hemangiopericytomas (HPCs) and found that 16 of the tumors (64%) showed immunoreactivity for PGDS in the perinuclear region. For comparison, 15 meningiomas, 14 soft-tissue HPCs, 1 mesenchymal chondrosarcoma, 3 choroid plexus papillomas, and 7 oligodendrogliomas were also examined. Meningiomas showed positive immunoreactivity for PGDS in 13 cases (80%). Except for one case located at the sacrum, none of the other soft-tissue HPCs showed immunostaining for PGDS. Mesenchymal chondrosarcoma arises in the bones of the skull, and its histological pattern resembles that of HPC; however, it showed no immunoreactivity for PGDS. Neither choroid plexus papillomas nor oligodendrogliomas were immunopositive for PGDS. These findings suggest that meningeal HPCs may have a unique molecular phenotype that is distinct from that of the soft-tissue HPCs. The origin of meningeal HPCs may be more closely related to the arachnoid cells.

Adolescent↗
PubMed2001

Anti-obesity effects in rodents of dietary teasaponin, a lipase inhibitor.

OBJECTIVE: Based on the inhibitory effects of teasaponin on pancreatic lipase activity in vitro, this study was performed to clarify whether teasaponin prevented obesity induced in mice by a high-fat diet for 11 weeks. DESIGN: For in vitro experiments, assay for the inhibitory effects of teasaponin on pancreatic lipase activity was performed by measuring the rate of release of oleic acid from triolein in an assay system using triolein emulsified with lecithin, gum arabic, Triton X-100 or 4-methylumbelliferyloleate. For in vivo experiments, female ICR mice were fed a high-fat diet with or without 0.5% teasaponin for 11 weeks. RESULTS: Teasaponin competitively inhibited the hydrolysis of triolein emulsified with lecithin, gum arabic, Triton X-100 or 4-methylumbelliferyloleate. Teasaponin inhibited the elevations of plasma triacylglycerol levels 3, 4 and 5 h after oral administration of lipid emulsion containing corn oil. Teasaponin suppressed the increases in body, parametrial adipose tissue weights and diameter in adipose cell size induced by a high-fat diet. Furthermore, feeding a high-fat diet plus teasaponin had no effect on stool frequency and content, but significantly increased triacylglycerol contents in feces as compared to feeding a high-fat diet. CONCLUSIONS: The anti-obesity effects of teasaponin in high-fat diet-treated mice may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity.

Animals↗
PubMed2001

The mechanism of epidermal hyperpigmentation in dermatofibroma is associated with stem cell factor and hepatocyte growth factor expression.

Dermatofibromas have an increased brownish color due to hyperpigmentation of the overlying skin. To determine paracrine factors involved in the epidermal hyperpigmentation, we have studied the expression of cytokines in lesional and nonlesional dermatofibroma skin at the transcriptional and protein levels using reverse transcription polymerase chain reaction and immunohistochemistry, respectively. The number of tyrosinase immuno-positive melanocytes in the pigmented dermatofibroma epidermis is significantly increased (2-fold) compared with nonlesional normal epidermis. Reverse transcription polymerase chain reaction analysis of mRNAs encoding stem cell factor and hepatocyte growth factor demonstrated that there is an accentuated expression of stem cell factor and hepatocyte growth factor transcripts in the lesional dermatofibroma dermis compared with the nonlesional dermis, although there is no difference in their expression between the lesional and nonlesional epidermis. In contrast, mRNA transcripts encoding endothelin-1, growth-related oncogene alpha, and basic fibroblast growth factor are not increased in lesional epidermis or in dermis relative to nonlesional skin. In parallel, immunohistochemical analysis using antibodies to stem cell factor and hepatocyte growth factor reveal a marked immunostaining in growing fibroblastic tumor cells in the dermatofibroma lesions with no detectable staining in the nonlesional dermis, but there is no difference in their immunostaining between the lesional and nonlesional epidermis. Interestingly, and consistent with the increased expression of stem cell factor in lesional dermatofibroma dermis, toluidine blue staining in the dermis revealed a 5-fold increase in the number of mast cells, an indication of their longevity or accumulation induced by stem cell factor. These findings suggest an important role of fibroblastic tumor cell-derived stem cell factor in the mechanism involved in the hyperpigmentation of the dermatofibroma epidermis.

Adult↗