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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 145 records · Page 8Linked to original sources

Epidemiological analysis of site relationships of synchronous and metachronous multiple primary cancers in the National Cancer Center, Japan, 1962-1996.

BACKGROUND: Multiple primary cancer (MPC) has been recognized as a problem commonly encountered in routine medical practice. A study of MPC is necessary not only to provide insights into the etiology of cancer, but also to provide information for effective medical care by clinical oncologists. METHODS: A cohort of 49,751 cancer patients who were admitted to the National Cancer Center Hospital between 1962 and 1996 was used to study the site relationship of MPC. Logistic and Poisson regression analyses using an internal reference group within the cohort were applied for the calculation of the prevalence odds ratio (POR) for site relationships of synchronous MPC and the incidence rate ratio (IRR) for those of metachronous MPC. RESULTS: Three site combinations with elevated risks for both synchronous and metachronous MPCs, eight with elevated risk for synchronous MPC, five with elevated risk for metachronous MPC and six with decreased risk for synchronous MPC were identified with statistical significance. Among them, the increased risk of metachronous stomach cancer following lymphoma and myeoloma (POR = 1.0 and 1.1, P > 0.05; IRR = 2.5, P < 0.05) and the inverse site-correlation of synchronous MPC between [trachea, bronchus and lung] and other sites of the upper aerodigestive tract [lip, oral cavity and pharynx] (POR = 0.5 and 0.3, P < 0.05) and esophagus (POR = 0.7 and 0.3, P < 0.05) have not been reported previously. CONCLUSIONS: Our results suggest that interventions for lymphoma and myeloma might affect the development of subsequent stomach cancer and additional etiological factors other than tobacco smoking are associated with the development of cancer in the upper aerodigestive tract.

Cohort Studies↗

Long-term follow-up results of adult patients with acute lymphocytic leukemia or lymphoblastic lymphoma treated with short-term, alternating non-cross-resistant chemotherapy: Japan Clinical Oncology Group Study 8702. Lymphoma Study Group.

BACKGROUND: Patients with acute lymphocytic leukemia (ALL) and those with lymphoblastic lymphoma (LBL) have overlapping clinical and immunophenotypic features and they have been treated with the same or very similar chemotherapy regimens. The goal of this multi-institutional phase II trial was to evaluate the therapeutic efficacy of a short-term, six-drug chemotherapy regimen for adult patients with untreated ALL or LBL. METHODS: Forty-six eligible patients, 41 with ALL and five with LBL, were treated with a short-term (planned total therapy duration; 36-38 weeks), simplified chemotherapy program; two courses of VEPA-L (vincristine, cyclophosphamide, prednisolone, doxorubicin, I-asparaginase plus intrathecal methotrexate and prednisolone) followed by four courses of M-VEPA (methotrexate plus VEPA), without the traditional maintenance therapy using daily 6-mercaptopurine and weekly methotrexate. RESULTS: Thirty-six (78%; 95% confidence interval 64-89%) of the 46 eligible patients achieved complete remission (CR). Among the 36 patients who achieved CR, four (11%) died of treatment complications, 26 (72%) relapsed and six (17%) remain alive in continuous CR. The median survival for all 46 eligible patients is 14 months and the median disease-free survival (DFS) for the 36 patients who achieved CR is 11 months. The estimate of the proportion of survival at 7 years of all 46 eligible patients is 15% at a median follow-up time of 96 months and that of DFS of the 36 patients achieving CR is 17% at a median follow-up time of 93 months. Subgroup analysis showed that an elevated serum C-reactive protein (CRP) level, age of 30 years or older, the presence of B-symptom and T-cell phenotype were likely to be associated with shortened survival. Although the observed CR rate (78%) is within the range of satisfaction, the long-term survival rate (15%) is inferior to those of published programs incorporating maintenance therapy. CONCLUSIONS: A fraction of adult patients with ALL or LBL are curable with a short-term, six-drug chemotherapy regimen. However, this simplified therapy of shorter duration cannot be recommended.

Adolescent↗

In vivo rat closed spinal window for spinal microcirculation: observation of pial vessels, leukocyte adhesion, and red blood cell velocity.

OBJECTIVES: An in vivo closed spinal window technique in rats was designed for observing the spinal microcirculation, such as the change of vessel diameter, leukocyte adhesion, and red blood cell (RBC) velocity, which has been very rarely examined in vivo in the spinal cord. METHODS: We made a very precise closed spinal window with a laminectomy at the C5 level using a dental acrylic resin and a cover glass (7 mm in diameter). Through this closed window, the dorsal surface of the rat cervical cord was observed with a video microscope, and the fluorescent images of rhodamine 6G-labeled leukocytes and fluorescein isothiocyanate-labeled RBCs were recorded and analyzed with a silicon-intensified target tube camera (30 frames/s) and an image-intensified high-speed video camera system (1000 frames/s). RESULTS: During CO2 inhalation, the pial arterioles responded with vasodilation of 12.4+/-10.4% (P<0.01) in 11 arterioles of seven rats. The adhering leukocytes significantly increased in 41 venular segments of seven rats after superfusion of the neutrophil chemoattractant, N-formyl-methionine-leucine-phenylalanine solution for 15 minutes (P<0.001) but not after superfusion of only artificial cerebrospinal fluid for 15 minutes. During these experiments, no adhering leukocyte was seen in the pial arterioles. Fluorescein isothiocyanate-labeled RBCs look like shooting stars in arterioles with silicon-intensified target tube camera processing at 30 frames per second, but individual fluorescein isothiocyanate-labeled RBCs could be recognized frame by frame with the image-intensified high-speed video camera system. In 13 arterioles of four rats, the RBC velocity was 5.3+/-2.0 mm per second. CONCLUSION: This closed spinal window technique in rats is available and applicable for the study of the spinal microcirculation, such as the pathophysiology of a secondary injury.

Animals↗

Lack of synchrony among multiple nuclei induces partial DNA fragmentation in V79 cells polyploidized by demecolcine.

The nuclear morphology of polyploidized cells was examined in V79 Chinese hamster cells polyploidized by demecolcine or K-252a, inhibitors of spindle fibre formation and protein kinases, respectively. A variety of nuclear morphologies, including multinuclei, were observed in V79 cells polyploidized by demecolcine but not by K-252a, which produced mononuclear cells. A lack of synchrony in the nuclear cycle was observed among nuclei in multinuclear polyploidized cells. Partial DNA fragmentation, defined as DNA fragmentation of a nucleus in a multinuclear cell, was detected using the TUNEL method in V79 cells polyploidized by demecolcine but not by K-252a. Apoptosis occurred earlier in cell populations treated with demecolcine than in these treated with K-252a once the drugs were removed from the medium, suggesting that polyploidized cells with separate nuclei tend to apoptose earlier than those with mononuclei.

Animals↗

Decrease in the prevalence of IL-4-producing CD4+ T cells in patients with advanced stage of primary biliary cirrhosis.

OBJECTIVE: To elucidate the precise immunological features in primary biliary cirrhosis (PBC), we examined the relative prevalence of CD4+ T cells in either symptomatic PBC (sPBC) or asymptomatic PBC patients (aPBC), and furthermore, these results were compared with their histological features. METHODS: Cytokine synthesis of peripheral blood mononuclear cells obtained from 24 PBC patients (9 sPBC and 15 aPBC) were examined by intracellular staining method. The relative prevalence of three distinct CD4+ T cells, gamma-interferon (IFN-gamma)-producing cells (Th1), interleukin-4 (IL-4)-producing cells (Th2), and the cells producing both IL-4 and IFN-gamma (Th0), was analyzed by FACScan and compared with those of closely age-matched healthy and disease controls. RESULTS: The results demonstrated that although a significant difference was not observed in the prevalence of Th1 or Th0, a remarkable difference was observed in the prevalence of Th2 (1.2+/-0.7 in sPBC, 4.1+/-1.3 in healthy subjects, 4.1+/-2.1 in aPBC, 3.4+/-1.3 in chronic hepatitis C, and 3.6+/-2.3 in cirrhosis secondary to CH-C; p < 0.05 for sPBC vs all others). Histological examination of these patients showed that all aPBC patients belonged to relatively early stage (stage I-II) and 7 of 8 sPBC patients belonged to late stage (stage III-IV). Thus, our results suggest that, mainly as a result of the decline of Th2, a predominance of Th1 may exist in advanced stage PBC. CONCLUSIONS: The present results demonstrated that a slight elevation of Th1 prevalence, as well as a significant decline of Th2 prevalence, was observed in peripheral blood of advanced stage PBC.

Adult↗

Uncertainty in risk characterization of weak carcinogens.

Epidemiologic inference is subject to uncertainty that is inherent to observational approaches. It was shown by the present analysis that an SMR of 1.4, as observed for 2,3,7,8-tetrachlorodibenzo-para-dioxin in the pooled analysis by IARC, would be observed in the absence of carcinogenic risk, if the smoking prevalence of cohort members was as low as 80%. It was also shown that a 1.4-fold increase in lung cancer risk among nonsmokers, which roughly corresponds to a daily consumption of one cigarette, might be extremely difficult to identify if the subjects are exposed to strong carcinogens such as those that result from cigarette smoking. On the other hand, a genotoxic agent that increases the lung cancer risk of smokers 1.4-fold, could increase the risk to nonsmokers by as much as 6.3-fold. In light of these uncertainties in epidemiologic inference, attempts to estimate the absolute risk in human populations by epidemiologic studies should be made with caution.

Carcinogens↗

Modulation of adrenal catecholamine release by PACAP in vivo.

The aim of the present study was to investigate whether pituitary adenylate cyclase-activating polypeptide-(1-27) (PACAP27) can modulate the adrenal catecholamine (CA) secretion induced by splanchnic nerve stimulation (SNS) and by exogenous acetylcholine (ACh) in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were quantified by a high-performance liquid chromatography coupled with electrochemical detection. Adrenal venous blood flow was measured by gravimetry. Local infusion of PACAP27 (0.5, 5, and 50 ng) to the left adrenal gland via the adrenolumbar artery resulted in an increase in CA output, reaching a significant level at the highest dose tested. Either direct SNS (2 Hz) or local infusion of ACh (0.5 microgram) to the left adrenal gland produced significant increases in CA output to an extent similar to that obtained with 50 ng of PACAP27 alone. In the presence of PACAP27 (50 ng), CA responses to either SNS or exogenous ACh were significantly potentiated by approximately four- and sixfold, respectively, compared with those obtained in response to each stimulus alone. However, the enhanced CA responses to ACh were not significantly different from those to SNS. The results indicate that the increase in adrenal CA secretion, induced by either direct SNS or exogenous ACh, is synergistically enhanced by PACAP27. The study suggests that the enhanced CA secretion may result from the activation of a PACAP-mediated facilitatory mechanism(s) localized presumably at the postsynaptic level in the canine adrenal medulla in vivo, although the possible involvement of presynaptic mechanisms cannot completely be ruled out in the present study.

Acetylcholine↗

Effects of moderate hypothermia on leukocyte- endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion.

Background and Purpose--It has been demonstrated that moderate hypothermia attenuates brain damage, but the mechanism whereby this is achieved has not been clearly shown. Recently, the role of leukocytes as mediators of secondary brain damage after brain ischemia has been discussed. The aim of this study is to examine the effects of moderate hypothermia on leukocyte-endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO). Methods--Rhodamine 6G-labeled leukocytes in brain surface were visualized with intravital fluorescence videomicroscopy through a closed cranial window. We analyzed the number of leukocytes adhering to the venular and arteriolar endothelium before ischemic insult and up to 3 hours after reperfusion. Rats were divided into 4 experimental groups. Group I (n=6) consisted of sham-operated animals. Groups II (n=6) and III (n=6) received left MCAO for 1 hour under normothermia (36 degrees C to 37 degrees C, group II) and under moderate hypothermia (30 degrees C to 32 degrees C, group III). Group IV (n=4) received left common carotid artery occlusion for 1 hour under normothermia. Results--The number of adhering leukocytes in venules in groups II and IV increased significantly (P<0.001) after reperfusion compared with the group I, but that in group III did not increase significantly (P>0.05). The number of adhering leukocytes in arterioles in group II increased significantly (P<0.01) compared with the other groups, although the adhering leukocytes were not as numerous as those seen in venules. Conclusions--It is demonstrated that hypothermia attenuates adhering leukocytes in venules and arterioles after reperfusion of MCAO. The inhibition of the leukocyte function may be an important factor in the neuroprotective effect of hypothermia.

Animals↗

A new member of the GP138 multigene family implicated in cell interactions in Dictyostelium discoideum.

The cellular slime mold Dictyostelium discoideum reproduces sexually under submerged and dark conditions. Its mating system is polymorphic and particularly interesting with respect to mechanisms of cell recognition. The cell-surface glycoprotein gp138 has been implicated in sexual cell interactions, as it was identified as a target molecule for the antibodies that block sexual cell fusion in D. discoideum. Two mutually homologous genes, GP138A and GP138B, have been cloned, but gene disruption experiments to clarify their functional relationships suggested that there is at least one more gene for gp138. Further protein analysis including peptide mapping also revealed that gp138 exists as three isoforms, DdFRP1, DdFRP2, and DdFRP3. GP138A encodes DdFRP2 and GP138B, DdFRP3, and the presence of a third gp138 gene encoding DdFRP1 was suggested. Here, we isolated and characterized a third GP138 gene, GP138C. Although the deduced amino acid sequences of GP138C matched completely with those of peptide fragments of DdFRP1 in the N-terminal half, the rest did not give complete matches. Overexpression of GP138C caused an increase in the intensity of DdFRP1, but disruption of this gene did not diminish DdFRP1. Our results indicate that GP138C encodes a protein very similar to but distinct from DdFRP1. The GP138 multigene family is thus composed of more members than previously expected, and their functional relationships are of special interest.

Amino Acid Sequence↗

Both low and high concentrations of staurosporine induce G1 arrest through down-regulation of cyclin E and cdk2 expression.

Staurosporine has been reported to cause arrest of cells in G1 phase at low concentration and in G2 phase at high concentration. This raises the question of why the effects of staurosporine on the cell cycle depend on the applied concentration. In order to verify these multiple functions of staurosporine in Meth-A cells, we used cyclin E as a landmark of G1/S transition, cyclin B as a landmark of G2/M transition and MPM2 as a hallmark of M phase. We found that staurosporine arrested cells in G1 phase at a low concentration (20 nM) and in G2/M phase at a high concentration (200 nM). However, 200 nM staurosporine increased the expression of cyclin B and cdc2 proteins, suggesting that the cells progressed through the G2/M transition, and increased the expression of MPM2 protein, indicating that the cells entered M phase. Moreover, 200 nM staurosporine increased the expression of p53 and p21 proteins and inhibited the expression of cyclin E and cdk2 proteins, suggesting that the cells were arrested in the G1 phase of the next cycle. Morphological observation showed similar results as well. These data suggest that the G2/M accumulation induced by 200 nM staurosporine does not reflect G2 arrest, but rather results from M phase arrest, followed by progression from M phase to the G1 phase of the next cycle without cytokinesis, and finally arrest of the cells in G1 phase.

Animals↗

[Effects of mouth wash on the removing beclomethasone dipropionate delivered by pressurized aerosol metered-dose inhaler in the mouth].

Effects of mouth wash (mouth rinsing and gargling) on the removal of drug residues in both mouth and pharynx after the use of pressurized aerosol metered-dose inhaler (MDI) were studied. The concentration of beclomethasone dipropionate (BM) in mouth wash after a splay of Becotide inhaler was measured by the method using HPLC. The total amount of the removed BM was measured by a sum of the concentrations of BM in 4 or 5 times of mouth washes in the following 4 kinds of methods. In method 1, mouth wash was done with 5 times of water change after a splay of MDI on wetted mouth. In method 2, mouth wash was done with 5 times of change water on dried mouth. In method 3, mouth wash was done with 4 times of change saliva on wetted mouth. In these methods, the actual inhalation of BM was not done. In method 4, mouth wash was done with 5 times of change water after a splay and a inhalation on wetted mouth. The mouth wash procedures removed totally 47.9%, 51.1%, 31.3%, and 33.3% of a splayed amount of BM in each method, respectively. It was required for the removal of 90% of the totally recovered BM to do one time of mouth wash in method 1, two times in method 2, three times in method 3, and two times in method 4, respectively. These data suggest that the mouth wash procedure is shown to have prophylactic benefit for candidiasis induced by steroid delivered by MDI.

Administration, Inhalation↗

Expression of cytokine and adhesion molecule mRNA in atherectomy specimens from patients with coronary artery disease.

Coronary arteriosclerosis is an underlying condition in acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP), and is also related to restenosis (RS) following coronary intervention. To investigate the pathogenesis of this condition, a quantitative reverse transcriptase polymerase chain reaction was used to determine relative levels of mRNA for interleukin (IL)-1beta, IL-6, IL-8, transforming growth factor beta (TGF-beta), intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 using directional coronary atherectomy (DCA) specimens. Eleven patients with AMI, 7 with UAP, 10 with SAP and 6 with RS following a previous coronary intervention underwent DCA. The mRNA intensity for each molecule was expressed by comparing it with that of beta-actin mRNA. The AMI and UAP patients showed high frequencies of mRNA for IL-1beta, IL-8, TGF-beta, and ICAM-1 together with strong intensities of expression, whereas SAP patients showed decreased mRNA expression for these molecules. Increased IL-6 mRNA expression was observed only in AMI samples. Specimens from RS patients revealed an accumulated expression of proinflammatory cytokines, except for IL-6, as well as of TGF-beta. The study suggests that variation in mRNA expression may reflect the pathophysiology of specific types of coronary artery disease, and remodeling following vascular injury.

Aged↗

Regulation of depolarization-induced calcium release from skeletal muscle triads by cyclic AMP-dependent protein kinase.

cAMP activated Ca2+ release from the sarcoplasmic reticulum (SR) triggered by transverse tubular membrane depolarization monitored in a triadic vesicle prepared from rabbit skeletal muscle. A kinetic analysis showed that the activation was in the amounts of released Ca2+ and not in the release rates. This activation was found to be depolarization-dependent, that is, the activation effect of cAMP decreased with an increase in the magnitude of depolarization. Because the activation was abolished by a protein kinase inhibitor, protein phosphorylation by the endogenous cAMP-dependent protein kinase (PKA) was thought to be in effect. On the contrary, caffeine-induced Ca2+ release was not activated by cAMP; however, the exogenous PKA catalytic subunit activated Ca2+ release, and this effect was probably through the phosphorylation of the SR Ca2+ release channel as described elsewhere. These results suggest that the protein, except for the SR Ca2+ release channel, is phosphorylated by endogenous PKA and plays a modulatory role in depolarization-induced Ca2+ release, that is, excitation-contraction coupling of the skeletal muscle.

Animals↗

Possible protective effect of milk, meat and fish for cerebrovascular disease mortality in Japan.

Cerebrovascular disease was a leading cause of death from 1955 to 1980 in Japan. The mortality rate from this disease has decreased sharply in recent decades. This downward trend seems to correspond to the dietary habits of Japanese. Data from a large prospective cohort study were analyzed to examine the association between dietary habits and cerebrovascular disease mortality in Japan. The subjects for this analysis were 223,170 men and women aged 40 to 69 at baseline in December 1965. There were 6,168 deaths in men and 4,862 deaths in women due to cerebrovascular disease (ICD7: 330-334) during the follow-up period from January 1966 to December 1981. Rate ratio (RR) and 95% confidence interval (95% CI) adjusted for sex, attained age, follow-up period, prefecture, cigarette smoking, alcohol drinking and occupation was used for comparison. In this study, the risk of mortality from cerebrovascular disease was inversely associated with dairy milk, meat and fish consumption. Therefore the joint effect of dairy milk, meat and fish (DMF) as animal fat and protein was of interest. In the binary analysis, DMF (D, M, F) means the combination of dairy milk (1-3 times/week or more), meat (1-3 times/week or more) and fish (4 times/week or more). Thus DMF (d, m, f) was the reference group having dairy milk (less than 1 time/week), meat (less than 1 time/week) and fish (less than 4 times/week). For the disease, the RR of DMF (D, M, F) was 0.68 with 95% CI of 0.63 to 0.74, relative to the reference group. Furthermore the joint effect of DMF was more strongly associated with cerebral haemorrhage (ICD7: 331, DMF (D, M, F); RR: 0.63, 95% CI: 0.55-0.70) than with cerebral embolism and thrombosis (ICD7: 332, DMF (D, M, F); RR: 0.79, 95% CI: 0.70-0.89). These findings suggest that the increasing intake of animal fat and/or protein may have played a key role in reducing cerebrovascular disease in Japan.

Adult↗

Ultraviolet radiation and health: from hazard identification to effective prevention.

The increased exposure to ultraviolet (UV) radiation due to ozone depletion is one of the most serious global health problems. The UV exposure is known to cause skin carcinoma, cataract and deteriorated immune function, but for countries like Japan, the magnitude of health effects of UV radiation is yet to be elucidated. The International Workshop on the Health Effects of Ultraviolet Radiation was held in Tokyo, Japan, on February 17-19, 1999, in attempts to visualize the size of this problem and to identify better solutions. Through this workshop, several lines of scientific evidence were provided, which clearly show that the risk of cataract and skin cancer among people living in Japan increases with the increasing level of sun exposure. We must seek, therefore, the extent to which the UV exposure of given intensity causes adverse health effects in Japanese population. Through the workshop, the importance of preventive measure was confirmed. The scientific basis of prevention is, of course, the knowledge of dose-response relationship and the current exposure status in Japanese population. It is hoped that the communications between researchers in Japan and other countries are strengthened through this workshop.

Cataract↗

Regional correlation between estimated UVB levels and skin cancer mortality in Japan.

Most ecological studies investigating the relationship between incidence and/or mortality of skin cancer and surrogate measures of ultraviolet radiation B (UVB) have been conducted among the Caucasian population. The objective of the present study was therefore to assess the geographical correlation between ambient UVB estimates and regional mortality rates for skin cancer in Japan. The standardized mortality ratio (SMR) for malignant melanoma and other malignant neoplasms of the skin was calculated by sex, region and time-period for all deaths occurring in the period 1973-1994. The Spearman's correlation coefficient was calculated between estimated ambient UVB and regional SMRs for the two types of skin cancer. There was no geographical correlation between UVB and skin cancer mortality, except for a significantly negative correlation in malignant melanoma among males and a significantly negative correlation in other malignant neoplasms of the skin confined to unexposed anatomic sites of the body among females. The characteristic ecological relationship adds to the importance of conducting further epidemiological studies at the individual level in Japan.

Age Distribution↗

Influence of chronic UV exposure and lifestyle on facial skin photo-aging--results from a pilot study.

In order to better understand the effect of chronic sun exposure on facial skin photo-aging and to identify the factors affecting it, we planned a study in two areas in Japan, Akita and Kagoshima, which correspond to the low and high sun exposure environments, respectively. As a first step, we conducted a pilot study in the two areas, examining 195 subjects. Hyper-pigmentation and wrinkling were measured with a high-resolution digital video imaging system. As expected, people in Kagoshima had darker skin, higher visual grades of facial hyper-pigmentation, and more facial wrinkles than people in Akita, reflecting the difference of UV exposure levels in the two areas. Both the grades of hyper-pigmentation and number of wrinkles increased in a roughly linear fashion with the advancement of age. On the other hand, the effect of gender was different in those two skin photo-aging parameters. Women had higher hyper-pigmentation grades (P = 0.012) and less wrinkles (P = 0.004) than men. Interestingly, post-menopausal women had higher grades of hyper-pigmentation than pre-menopausal women. Neither sun exposure index for darkness nor wrinkling showed any significant differences by menopausal status. In this pilot study, we collected information on various factors, including life-styles. The results of detail analysis will be presented elsewhere. In the present analysis, we found that the grade of hyper-pigmentation was not related to total hours spent outside in life but was affected by various factors, including toe-nail zinc levels. On the other hand, the number of wrinkles was significantly related to total hours spent outside in life. The most important risk factors of non-melanoma skin cancer are chronic sun exposure, age and male sex. All of them are strongly related to higher levels of UV exposure. The present study confirmed that chronic sun exposure, age and male sex were strong risk factors of the wrinkle number. The number of wrinkles was significantly related to total hours of sun exposure in life, increased in a roughly linear fashion with the advancement of age, and was larger in men than in women. In epidemiological studies of UV-related skin cancer, the number of wrinkles, which can be easily measured with a high-resolution digital video imaging system as shown in this study, may be a good marker of total sun exposure in life.

Adult↗