Analysis of morphological changes after facial massage by a novel approach using three-dimensional computed tomography.

BACKGROUND/PURPOSE: Photograph-based visual scoring has been used for evaluation of facial morphological changes. Here, we describe a three-dimensional computed tomography (3D-CT) method for objective analysis of facial and intra-facial (subcutaneous) changes. The effects of facial massage were examined using both methods. METHODS: Subjects were 12 healthy female volunteers without facial scars or deformation (age 30-54 years, mean 39.4 years). Photograph-based scoring of massage-induced morphological changes was done at the nasolabial folds, upper, lower and lateral cheeks and lower eyelids. For 3D-CT evaluation, the virtual center axis (VCA) was set as the cranio-caudal longitudinal line, and the VCA-skin surface distances (VSDs) were measured. Massage-induced changes of VSD were calculated (facial massage-induced change rate, FMCR). Intra-facial (subcutaneous) changes were also evaluated. RESULTS: Photograph-based scoring revealed marked morphological changes of the nasolabial folds after facial massage, and changes of the lower, upper and lateral cheeks and lower eyelid were also observed in more than half of the subjects. FMCR values were significantly changed in the paranasal area, nasolabial fold area and cranial part of the mandibular area. Photograph-based scores at the lower cheek and lower eyelid were well correlated with FMCR in the inferior part of the nasolabial fold and the mandibular area, respectively. Massage-induced changes of subcutaneous fat tissues and facial expression muscles were also apparent on CT images. CONCLUSION: 3D-CT imaging is useful for objective evaluation of the effects of facial massage, including anatomical changes in subcutaneous structures.

Analysis of c-KIT exon 11 mutations in canine gastrointestinal stromal tumours.

The aim of this study was to determine the type and frequency of c-KIT exon 11 mutations in canine gastrointestinal stromal tumours (GISTs) and investigate the association between the c-KIT mutation status and KIT immunohistochemical staining pattern. Mutations in exon 11 of c-KIT were examined in 46 formalin-fixed paraffin-embedded canine GISTs using PCR of genomic DNA and reverse transcription-PCR (RT-PCR) of cDNA. Exon 11 c-KIT mutations were detected in 15/46 (32.6%) cases by conventional PCR and 34/46 (73.9%) cases by RT-PCR; the mutation detection rate was significantly higher for RT-PCR (P = 0.004, Fisher's exact test). Ten different mutations, including deletion, internal tandem duplication and point mutations, were identified by RT-PCR. Immunohistochemistry was performed using an anti-KIT antibody; diffuse KIT staining was detected in the tumour cell cytoplasm in 32/46 (69.6%) cases and partial or stippled cytoplasmic staining of KIT was observed in 14/46 (30.4%) cases. Neither pattern was significantly associated with c-KIT exon 11 mutation status (P = 1.000, chi-square test). These data indicate that c-KIT exon 11 mutations occur frequently in canine GISTs, similar to human GISTs; however, there is no association between c-KIT mutations and the KIT expression pattern in canine GISTs. This study suggests that RT-PCR is more sensitive than conventional PCR for the detection of c-KIT mutations in canine GISTs.

Dermal anchoring structures: convex matrix structures at the bottom of the dermal layer that contribute to the maintenance of facial skin morphology.

BACKGROUND/PURPOSE: Facial skin must be linked to underlying structures to maintain facial morphology and prevent sagging, but the mechanism of facial skin retention is largely unknown. We aimed to elucidate this mechanism. METHODS: Twenty-two cheek skin specimens (age range: 10s-60s, both genders) were observed histologically. And 30 cheek of healthy Japanese volunteers (age range: 30s-50s, female) was photographed and the severity of sagging was graded. Dermal layer morphology was observed non-invasively with ultrasound. Skin-retaining force was measured with a Cutometer MPA 580(®) , and sagging severity was evaluated by grading criteria. RESULTS: Histological observation revealed characteristic convex structures at the bottom of the dermal layer. Non-invasive study showed that the depth of the convex structures, measured by ultrasonography, was significantly negatively related to the ratio of viscoelastic to elastic distention (Uv/Ue) and positively related to the ratio of elastic recovery to total deformation (Ur/Uf) at the cheek of female volunteers, measured by cutometer. It was also negatively related to sagging severity. Further, Ur/Uf was negatively and Uv/Ue was positively related to sagging severity. CONCLUSION: Characteristic convex structures at the bottom of the dermal layer serve as anchoring structures to maintain skin morphology.

Effect of secondary particles on image quality of dynamic flat panels in carbon ion scanning beam treatment.

OBJECTIVE: Real-time markerless tumour tracking using radiographic fluoroscopic imaging is one of the better solutions to improving respiratory-gated radiotherapy. However, particle beams cause secondary particles from patients, which could affect radiographs. Here, we evaluated the quality of radiographs during carbon ion pencil beam scanning (CPBS) irradiation for respiratory gating. METHODS: A water phantom and chest phantom were used. The phantoms were irradiated with CPBS at 290 MeV n(-1) from orthogonal directions. Dose rates were 3.4 × 10(8), 1.14 × 10(8) and 3.79 × 10(7) particles per second. A dynamic flat panel detector (DFPD) was installed on the upstream (DFPD1) or downstream (DFPD2) side of the vertical irradiation port. DFPD images were acquired during CPBS at 15.00, 7.50 and 3.75 frames per second (fps). Charge on the DFPD was cleaned using fast readout technique every 30 fps. DFPD images were acquired during CPBS with radiographic exposure, and results with and without fast readout technique were compared. RESULTS: Secondary particles were visualized as spots or streak-like shapes. Capture of secondary particles from the horizontal beam direction was lower with fast readout technique than without it. With regard to beam irradiation direction dependency, CPBS from the horizontal direction resulted in a greater magnitude of secondary particles reaching DFPD2 than reaching DFPD1. When CPBS was delivered from the vertical direction, however, the magnitude of secondary particles on both DFPDs was very similar. CONCLUSION: Fast readout technique minimized the effect of secondary particles on DFPD images during CPBS. ADVANCES IN KNOWLEDGE: This technique may be useful for markerless tumour tracking for respiratory gating.

Effectiveness of female community health volunteers in the detection and management of low-birth-weight in Nepal.

INTRODCTION: Low birth weight (LBW) is a major risk factor for neonatal death. However, most neonates in low-income countries are not weighed at birth. This results in many LBW infants being overlooked. Female community health volunteers (FCHVs) in Nepal are non-health professionals who are living in local communities and have already worked in a field of reproductive and child health under the government of Nepal for more than 20 years. The effectiveness of involving FCHVs to detect LBW infants and to initiate prompt action for their care was studied in rural areas of Nepal. METHODS: FCHVs were tasked with weighing all neonates born in selected areas using color-coded spring scales. Supervisors repeated each weighing using electronic scales as the gold standard comparator. Data on the relative birth sizes of the infants, as assessed by their mothers, were also collected and compared with the measured weights. Each of the 205 FCHVs involved in the study was asked about the steps that she would take when she came across a LBW infant, and knowledge of zeroing a spring scale was also assessed through individual interviews. The effect of the background social characteristics of the FCHVs on their performance was examined by logistic regression. This study was nested within a community-based neonatal sepsis-management intervention surveillance system, which facilitated an assessment of the performance of the FCHVs in weighing neonates, coverage of FCHVs' visits, and weighing of babies through maternal interviews. RESULTS: A total of 462 babies were weighed, using both spring scales and electronic scales, within 72 hours of birth. The prevalence of LBW, as assessed by the gold standard method, was 28%. The sensitivity of detection of LBW by FCHVs was 89%, whereas the sensitivity of the mothers' perception of size at birth was only 40%. Of the 205 FCHVs participating in the study, 70% of FCHVs understood what they should do when they identified LBW and very low birth weight (VLBW) infants. Ninety-six per cent could describe how to zero a scale and approximately 50% could do it correctly. Seventy-seven per cent of FCHVs weighed infants at least once during the study period, and 19 of them (12%) miscategorized infant weights. Differences were not detected between the background social characteristics of FCHVs who miscategorized infants and those who did not. On the basis of maternal reporting, 67% of FCHVs who visited infants had weighed them. CONCLUSIONS: FCHVs are able to correctly identify LBW and VLBW infants using spring scales and describe the correct steps to take after identification of these infants. Use of FCHVs as newborn care providers allows for utilization of their logistical, geographical, and cultural strengths, particularly a high level of access to neonates, that can complement the Nepalese healthcare system. Providing additional training to and increasing supervision of local FCHVs regarding birth weight measurement will increase the identification of high-risk neonates in resource-limited settings.

International models of investigator-initiated trials: implications for Japan.

BACKGROUND: Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. MATERIALS: In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. RESULTS: In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. CONCLUSIONS: To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval.

Body cavity fluid can induce epithelial and mesothelial differentiation from CD34 positive peripheral blood stem cells in vitro.

OBJECTIVE: Primary culture of CD34 positive stem cells collected from human peripheral blood was performed with and without supplementation with concentrated ascitic fluid; morphological and immunocytochemical pictures of cultured cells were taken chronologically and compared. METHODS: CD34-positive stem cells collected from peripheral blood were cultured for 1, 24 and 48 hours. Concentrated ascitic fluid was added to the plates for the 24-and 48-hour cultures. For immunocytochemical studies, CD34, AE1/AE3, Ber-Ep4 (EA), EMA, EGFR, CD31, CA125 and D2-40 monoclonal antibodies were used. RESULTS: After culture, small round cells with naked nuclei began to enlarge and to exhibit various changes in the cytoplasm and nucleus. Supplementation with concentrated body cavity fluid enhanced these changes. CD34-positive cells with small round cell features were detected 1 hour after culture and these had no epithelial or mesothelial markers. After 24 hours, CD34-positive cells had disappeared and cells weakly positive for EGFR, EMA, CA125 and D2-40 were detected. Cells with strong and moderate positive reactions for EGFR, AE1/AE3, EA, EMA, D2-40 and CA125 were detected after 48 hours. Supplementation with concentrated body cavity fluid increased the intensity and number of positive cells for these markers compared with the control group. The positive reaction, not only for the epithelial markers such as EGFR and AE1/AE3, but also for mesothelial markers such as CA125 and D2-40, was found to be increased in small numbers of cells in direct proportion to the duration of the primary culture of the peripheral blood cells. CD31, characteristically expressed in endothelial cells, was negative in the cultured cells. CONCLUSION: Supplementation of peripheral blood CD34-positive stem cells with body cavity fluid in vitro enhanced their differentiation toward cells of an epithelial or mesothelial phenotype, concomitant with loss of immunoreactivity for CD34. It is assumed that the routine cytological observation of cells obtained from body cavity fluid might cause possible cytomorphological and immunophenotypical changes due to the action of the growth factors contained in the body cavity fluid.

Pinguecula and contact lenses.

PURPOSE: To assess the relationship between age and the incidence and severity (determined by a grading system) of pinguecula in contact lens (CL) wearers, and to compare the grade of pinguecula between CL wearers and non-wearers. METHODS: A total of 600 CL wearers (94 wore hard CLs (HCLs) and 506 wore soft CLs (SCLs)) aged 11-60 years and 579 non-wearers aged 10-60 years were enrolled. The age, gender, medical history, ocular history, and grade of pinguecula at two locations (nasal and temporal) were determined in all subjects. RESULTS: There was an age-related increase in the grade of pinguecula among both CL wearers and non-wearers. The grade of pinguecula at the temporal conjunctiva was higher in CL wearers than in non-wearers (P=0.01907), whereas it was higher in HCL wearers than SCL wearers at both the nasal and temporal conjunctiva (P<0.00001 and P<0.00001). CONCLUSIONS: This was the first assessment of the severity of pinguecula in a large consecutive series of CL wearers. Our results suggest that the use of CLs is an important risk factor for pinguecula.

Sagging of the cheek is related to skin elasticity, fat mass and mimetic muscle function.

BACKGROUND/PURPOSE: Facial sagging is associated with aging, although the mechanism remains unclear. The aim of this study was to investigate the mechanism of facial sagging by examining the relationship of sagging severity to changes of skin elasticity, fat mass and facial muscle function at the cheek. METHODS: Faces of 108 healthy Japanese female volunteers, aged 20-60 years were photographed at an angle of 45 degrees . Standard scores of sagging severity were established by analyzing the photographs. We examined the correlations of scored sagging levels with skin elasticity measured with a Cutometer MPA 580, fat content estimated by bioelectrical impedance analysis and facial muscle function (lip sealing force and occlusal force) in middle-aged female volunteers (30-40 years) with a wide range of sagging scores. RESULTS: Because the upper, lower and lateral areas in the cheek may show severe sagging, a six-grade score of sagging severity was separately established for each area. Each score was significantly correlated positively with age (20-60 years). In middle-aged volunteers, the sagging scores in all three areas of the cheek were significantly and negatively associated with skin elasticity. Body fat percentage was significantly and positively correlated with the sagging scores in the lower and lateral areas, although the correlation was only weakly positive in the upper area. Mimetic muscle function, measured in terms of lip sealing pressure, was significantly and negatively correlated with the sagging score only at the upper area of the cheek, but masticatory muscle function, measured in terms of occlusal force pressure, was not associated with the sagging score. CONCLUSIONS: Sagging may be associated with the reduction of skin elasticity and mimetic muscle function and increase of fat mass, but the relationships are different in different areas of the cheek.

Difference in the odor concentrations measured by the triangle odor bag method and dynamic olfactometry.

'The triangle odor bag method', which has been adopted for the offensive odor control law in Japan, and the dynamic olfactometry defined by EN 13725 have been compared. The odor concentration measured by the triangle odor bag method tends to be higher than that of the dynamic olfactometry in the forced choice mode, while well agreed in the Yes/No mode olfactometry when the panel is the same. The difference can be minimized by applying the panel selection criterion of EN13725 to the triangle odor bag method. The European panel selection test is useful to negate the difference in the measurement equipments although the criteria seem to be strict considering the individual threshold data of n-butanol.

Comparison of postoperative surface light scattering of different intraocular lenses.

AIMS: This retrospective study was conducted to compare postoperative surface scattering of four kinds of intraocular lens (IOL). METHODS: Sixty-seven eyes of 67 patients who had undergone cataract surgery were enrolled in this study. One of four IOLs was used in the patients; MA60BM in 17 patients (MA group), SA60AT in 17 patients (SA group), AR40 in 16 patents (AR group) and ClariFlex in 17 patients (CL group). Measurement of scattering from the anterior surface of the IOL was measured with area densitometry using a Scheimpflug camera (EAS-1000, Nidek, Aichi) for 3 years after the surgery. RESULTS: The density of IOL surface scattering increased starting 1 year after surgery and throughout the 3-year period in the MA group and starting at 6 months through 3 years in the SA group, whereas the density was stable in the AR and CL groups. The density of surface scattering in the MA and SA groups at 3 years after surgery was significantly higher than in the AR and CL groups. CONCLUSION: The surface scattering of MA60BM and SA60AT is higher than that of AR40 and ClariFlex. The grades of surface scattering differ among the manufacturers, even with the same acrylic material.

Relationship between refraction and allergic conjunctivitis.

PURPOSE: External allergens are the main causative factor in the pathogenesis of allergic diseases; however, little is known about internal factors such as the biometrical structure of the eye. We investigated the relationship between refractive error and allergic conjunctivitis in order to reveal possible insights into the pathogenesis in 1015 subjects. METHODS: The patients were divided into four groups: contact lens wearers with allergic conjunctivitis (n=73), contact lens wearers without allergic conjunctivitis (n=59), non-contact lens wearers with allergic conjunctivitis (n=224), and non-contact lens wearers without allergic conjunctivitis (n=659). The spherical power, cylindrical power, corneal radius, and minimum and maximum corneal refractive powers were measured in all subjects. RESULTS: In the non-contact lens wearers, the spherical equivalent and spherical power were significantly lower in patients with allergic conjunctivitis than in patients without allergic conjunctivitis (-3.01+/-3.83 D vs-1.36+/-3.08 D, P<0.0001, and -2.64+/-3.63 D vs-1.05+/-2.88 D, P<0.0001, respectively), while there was no significant difference in any of the parameters between the contact lens wearers with and without allergic conjunctivitis. CONCLUSION: Refractive error may be a risk factor for allergic conjunctivitis.

Longitudinal analysis of corneal topography in suspected keratoconus.

AIMS: To examine the incidence of progression of suspected keratoconus to true keratoconus and compare quantitative descriptors of corneal topography between eyes with and without progression. METHODS: 34 eyes with suspected keratoconus were retrospectively reviewed in 34 patients. Their age at the initial examination was 13 to 40 years (24.1 (7.5), mean (SD)), and the follow-up periods ranged from 3 to 10 years (6.0 (2.2) years). Suspected keratoconus was defined as the fellow eye of a clinically apparent keratoconus but that had no slit-lamp signs of keratoconus (Fleischer ring, Vogt striae and Munson sign) with a best spectacle-corrected visual acuity of 20/20 or better. Eyes were monitored for the progression of apparent slit-lamp findings of keratoconus during the follow-up period. Using a Fourier analysis of the corneal topography data, regular astigmatism, asymmetry component and higher-order irregularity component were calculated in the central 3 mm zone. Quantitative descriptors of corneal topography were compared between eyes which progressed to true keratoconus and those which did not. RESULTS: Five eyes (14.7%) progressed to apparent keratoconus from suspected keratoconus (progression group), and 29 eyes did not (non-progression group). On average, it took 5.2 years for the eyes to develop apparent slit-lamp findings of keratoconus. The cumulative incidence of progression by Kaplan-Meier analysis was 21.5% in 6 years. The asymmetry component and regular astigmatism by Fourier analysis at the initial examination were significantly larger in the progression group than in the non-progression group. CONCLUSION: In our retrospective study, approximately 20% of eyes with suspected keratoconus progressed to true keratoconus in 6 years, and these eyes had presented greater asymmetry and regular astigmatism at the initial examination.

Penetrating keratoplasty for bullous keratopathy after trabeculectomy.

PURPOSE: To evaluate the results of penetrating keratoplasty (PK) in eyes with bullous keratopathy having previously undergone trabeculectomy. METHODS: We reviewed medical records of patients that had undergone PK for bullous keratopathy having previously undergone trabeculectomy. A total of 34 eyes in 34 patients were included in the study. As a control group, we reviewed the medical records of 26 eyes in 26 patients that had no history of glaucoma and who had undergone PK for bullous keratopathy in the same period at the same institutes. Kaplan-Meier survival analysis was performed to estimate the cumulative probability of successful intraocular pressure (IOP) control, immune reaction-free graft, and graft survival. RESULTS: Visual acuity improved by more than two lines in 30-34 eyes (88%). Log-rank tests showed a statistically significant difference in the cumulative probability of successful IOP control between eyes with functioning blebs and eyes with non-functioning blebs (P=0.0005), but not between the experimental subjects of 34 eyes and the control group (P=0.198). The log-rank test did not show statistically significant differences in the cumulative probability of immune reaction-free grafts and graft failure between the subjects and the control group and between eyes with functioning blebs and eyes with non-functioning blebs. CONCLUSION: The outcomes for PK in bullous keratopathy are good for patients having previously undergone trabeculectomy. Surgical procedures should be performed before PK in eyes with non-functioning blebs even when IOP is controllable with medication.

Plasmin induces degradation and dysfunction of laminin 332 (laminin 5) and impaired assembly of basement membrane at the dermal-epidermal junction.

BACKGROUND: The epidermal basement membrane (BM), located at the dermal-epidermal junction (DEJ), plays important roles not only in adhesion between epidermis and dermis, but also in controlling skin functions. In sun-exposed skin, the BM becomes disrupted and multilayered. In order to explore the impairment of BM assembly, we have used a skin-equivalent (SE) as a model of BM damage and previously clarified the involvement of matrix metalloproteinases (MMPs) in impairment of BM assembly. OBJECTIVES: In this work, we examined the role of urokinase-type plasminogen activator (uPA) and plasmin in impairment of BM assembly at the DEJ by using the SE, as ultraviolet irradiation to the skin increases uPA as well as MMPs. METHODS: SEs were used as a model of formation and damage of BM. Human uPA was detected by enzyme-linked immunosorbent assay and zymography, and gelatinases such as MMP-2 and MMP-9 were detected by zymography. Human plasminogen was added at 0.06 micromol L(-1) (about 3% of plasma level) to increase plasmin to a pathological level. N-terminal peptide sequence analysis of plasmin-treated laminin 332 was carried out to identify alpha3, beta3 and gamma2 chains of laminin 332 and their cleavage sites of each chain. Plasmin-treated laminin 332 was analysed in keratinocyte adhesion activity and binding to type VII collagen. RESULTS: Human uPA was detected in addition to MMP-2 and MMP-9, in conditioned medium of SE. Although the BM was well organized in the presence of an MMP inhibitor alone, the activated plasmin disorganized the BM even in the presence of the inhibitor. The impairment of BM assembly made the epidermis thinner as compared with that of a control cultured in the presence of MMP inhibitor, indicating that the BM affects the polarity and differentiation of the epidermis. The addition of aprotinin, a serine proteinase inhibitor, and tranexamic acid, a uPA-plasmin inhibitor, inhibited the plasmin-induced impairment of BM assembly and facilitated BM reorganization, thereby improving the epidermal structure. N-terminal peptide sequence analysis of plasmin-treated laminin 332 revealed the removal of a 5- or 10-kDa fragment, including the cell adhesion region, from the G3 domain of the alpha3 chain, and the LN domain, which binds to the noncollagenous 1 domain in type VII collagen, from the beta3 chain. Plasmin-treated laminin 332 showed lower keratinocyte adhesion activity and reduced binding to type VII collagen. CONCLUSIONS: These results suggest that uPA and plasmin are involved in the impairment of BM assembly and epidermal differentiation, and that these effects arise at least partly through direct degradation of laminin 332.

Establishment of a mouse skin model of the lichenification in human chronic eczematous dermatitis.

BACKGROUND: Repeated mechanical stresses, such as scratching and rubbing, on a lesional skin area induce a rough skin condition known as lichenification in patients with chronic eczematous dermatitis. For ethical reasons, the pathomechanisms involved are difficult to study, so an animal model is required. OBJECTIVES: To study the pathomechanisms of the unique rough skin changes seen in chronic eczematous dermatitis, we established a mouse skin model by repeated tape stripping to inflict stratum corneum (SC) barrier disruption. The skin characteristics of the model were investigated biologically, histologically and pharmacologically. METHODS: Tape stripping was done on mouse back skin three times a week for 4 weeks. The skin changes were studied by obtaining negative replicas, haematoxylin and eosin staining, immunostaining for CD31 and BrdU, and measuring epidermal and cutaneous thickness and skin capacitance. Activities of matrix metalloproteinase (MMP)-2, 9 and urokinase-type plasminogen activator (uPA) in the skin tissues were analysed by zymography. The effects of MMP inhibitor and glycine were assessed. RESULTS: The repeated tape stripping produced crusting and desquamation at 48 h, followed 1 week later by the formation of shallow furrows, which became much deeper after 4 weeks, appearing as fine and regular wrinkles. The resultant wrinkled skin resembled lichenified skin seen in patients with chronic eczematous dermatitis. Histopathologically, we found acanthosis, hypergranulosis and hyperkeratosis even at 48 h, and the skin was 2.5 times thicker than untreated control skin at 4 weeks. We observed angiogenesis in the upper dermis at 1 and 4 weeks. Skin capacitance, a parameter of SC hydration, displayed consistently low levels throughout the experimental period. Although the dermis was also thickened, the activity of MMP-9 was sharply increased only at 24 and 48 h after tape stripping, declining thereafter to the control level. Topical applications of CGS-27023A (CGS), an MMP inhibitor, failed to suppress this tape-stripping-induced wrinkle formation. In contrast, topical applications of a barrier recovery accelerator, glycine, effectively inhibited the wrinkle formation induced by repeated tape stripping. CONCLUSIONS: The induction of fine and regular wrinkles by inflicting chronic SC barrier disruption in this model involves mainly epidermal changes, which is in sharp contrast to the mainly dermal changes induced by chronic ultraviolet B irradiation.