Growth dynamics among adolescent girls in Bangladesh: Evidence from nationally representative data spanning 2011-2014.

BACKGROUND: Adolescence is the last opportunity to reverse any growth faltering accumulated from fetal life through childhood and it is considered a crucial period to optimize human development. In Bangladesh, a growing double burden of underweight and obesity in adolescents is recognized, yet limited data exists on how, when, and where to intervene. This study assesses the dynamics of growth among adolescent girls in Bangladesh, providing insight about critical junctures where faltering occurs and where immediate interventions are warranted. METHODS: We pooled data from Bangladesh's Food Security and Nutrition Surveillance Project collected between 2011 and 2014 to document the age dynamics of weight and linear growth. 20,572 adolescent girls were measured for height and 19,345 for weight. We constructed growth curves for height, weight, stunting, and underweight. We also stratified growth dynamics by wealth quintile to assess socioeconomic inequities in adolescent trajectories. RESULTS: Height-for-age z-score (HAZ) in Bangladeshi girls deteriorates throughout adolescence and especially during the early years. Mean HAZ decreases by 0.20 standard deviations (sd) per year in early adolescence (10-14 years) vs 0.06 sd/year during late adolescence (15-19 years), while stunting increases by 16 percentage points (pp) vs 6.7 pp, respectively. Conversely, BMI-for-age z-score (BAZ) increases by 0.13 sd/year in early adolescence vs 0.02 sd/year in late adolescence, and underweight decreases by 12.8 pp vs 3.2 pp. Adolescent girls in all socioeconomic groups show a similar pattern of HAZ and BAZ dynamics, but the curve for the richest quintile stays above that of the poorest across all ages. CONCLUSIONS: Trends and levels of stunting and underweight among adolescent girls in Bangladesh are worrisome, suggesting substantial linear growth faltering in early adolescence, with improving weight-for-age occurring only as linear growth slows and stops. Given the rising burden of non-communicable diseases (NCDs) in Bangladesh and emerging evidence of the link between stunting and later chronic diseases, greater attention to adolescent growth and development is needed. Our findings suggest that, to address stunting, interventions in early adolescence would have the greatest benefits. School-based interventions could be a way to target this population.

Low Cardiac Output Syndrome: Incidence after Mitral Valve Replacement with or without Preservation of Mitral Valve Apparatus.

Standard mitral valve replacement in patients with chronic mitral valve regurgitation and mitral valve stenosis consistently results in a decrease in early postoperative left ventricular ejection performance. Some studies showed that preservation of mitral valve leaflet and subvalvular apparatus can reduce postoperative left ventricular dysfunction. On the basis of the concept, this randomized clinical trial comparing mitral valve replacement with preservation of mitral subvalvular apparatus and conventional mitral valve replacement performed in National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh, in the period of July 2010 to December 2011. We included 60 patients of mitral regurgitation and mitral stenosis, among them 30 patients underwent mitral valve replacement with preservation of mitral subvalvular apparatus (Group A) and 30 patients underwent conventional mitral valve replacement (Group B). There was no significant difference between two groups in terms of peri-operative variables. But there was significant higher incidence of Low cardiac output (LOS) syndrome [36.7% vs. 6.9% (p<0.05)] and congestive heart failure in Group B than Group A. The duration of ICU stay was also significantly higher in conventional mitral valve replacement group [113.23±11.30 hours vs. 96.23±20.02 (p=0.001)]. Additionally, there was significantly less fall of left ventricular ejection fraction in preservation of mitral subvalvular apparatus group [preop 65.27±5.45, at discharge 54.31±3.78, after 3 months 58.28±5.20 (p<0.0001)] than conventional group [preop 66.43±4.58, at discharge 46.43±3.87, after 3 months 46.55±3.63 (p<0.0001)]. In this study left ventricular ejection fraction was used as measure of left ventricular function. We postulate that, this relative preservation of left ventricular ejection fraction was likely the result of preservation of mitral subvalvular apparatus.

Home Based Pulmonary Rehabilitation on Oxygenation Status, Dyspnea and Fatigue in Stable Patients with COPD.

Pulmonary rehabilitation (PR) program of a sufficient duration has impact on consequence of COPD. To evaluate the effects of combination of pursed lip breathing (PLB), diaphragmatic breathing (DB) and lower extremity endurance training (LEET) as part of PR program in stable patients with COPD on oxygenation status, dyspnea and fatigue. This prospective interventional study was performed in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from July 2010 to June 2011 and was performed on 116 male stable moderate COPD patients aged 50 to 65 years. Among them, 56 patients were without PR (control group) and 60 patients were intervened with PR (experimental group). The experimental patients were advised to perform the home based PR program (PLB, DB and LEET) for 30 minutes duration per session at home twice per day, along with standard drug treatment of COPD for uninterrupted 60 days. The control patients continued their treatment of COPD with standard drug for successive 60 days were advised. To evaluate the effects of PR, Peripheral capillary oxygen saturation (SpO2, by pulse Oximeter), level of dyspnea and level of fatigue by Modified Borg Scale from baseline to end of six minute walk test (6MWT) of all subjects were recorded on day 0 and day 60 for both the groups. Independent sample 't' test and paired Student's 't' test were done with SPSS software. In the interpretation of results, p value of <0.05 was considered as statistically significant. In the present study, we found less decrement of SpO2 and less increment of level of dyspnea as well as level of fatigue after 6MWT in the COPD patients with PR on 60th day of follow up. The study reveals that oxygenation status, dyspnea and fatigue improve after execution of regular home based PR program in patients with moderate stable COPD.

Pattern of Casualties Attending in the Casualty Department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh.

Casualty, in relation to personnel, any person who is lost to his organization; by reason of being declared dead, wounded, diseased, detained, captured or missing. Casualty service or department is not well organized in the hospitals of our country. We have recently started functioning casualty department to manage casualties properly in spite of the increasing workload and emerging needs of this department. This study was conducted in the Casualty department, Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh to analyze the number of patients and pattern of casualties. A total number of 17435 patients were enrolled in this retrospective observational study. Data was collected from hospital records of all patients attending in the Casualty Department, MMCH between November 19, 2017 and May 18, 2018 and patients were categorized on the basis of their mode of injury. The demographic characteristics of patients with mode of Casualty were analyzed. Male were 75% and female 25%. Avergae per day patient attended in the Casualty department was 96, maximum was 176 and minimum 33. According to age sub-division, 11-20 years age group attended maxiumum was 48. One day attended Road traffic accident (RTA) maximum was 65 and minimum was 3, Non-RTA maximum was 83 and minimum 25, physical assaults maximum was 48 and minimum 1. Injury due to fall and RTA were the common mode of casualty especially in the young population in the study area. Study showed that injury caused by fall was 44% among the all patients. Patients due to fall from tree was highest (35%) in April-May. Incidents of fall were followed by RTA which was 25%. Physical assaults (17%), machinery injury (9%) and others were 5%.

Breastfeeding and cognitive development of children: assessment at one year of age.

Breastfeeding is the fundamental component of child survival strategy. It significantly influences neurological development of children. The study was conducted to assess whether exclusive and prolonged breastfeeding improves children's cognitive development, including low birth weight (LBW) babies, in a developing country setting like Bangladesh. This observational study was done on a cohort of newborn infants who were discharged from the special care baby unit of Dhaka Shishu Hospital during January 2006 to December 2008 with proper counseling about exclusive and prolonged breastfeeding. Their neuro-developmental follow-up was started at 4 weeks postnatal age and continued at 3-monthly intervals up to 1 year of age. At each visit, cognitive development was assessed using the Bayley Scales of Infant Development (BSID II). Cognitive development was compared between the babies of exclusive vs. non exclusive breastfeeding, normal weight vs. low birth weight and male vs. female babies. A total of 105 cases were successfully followed-up during this period. Out of these 47(44.8%) babies were exclusively breastfed up to 6 month of age and 58(55.2%) were in nonexclusive group. Overall Psychomotor Development Index (PDI) was slightly more (108.40 ± 23.06 vs. 103.23 ± 19.87) in the exclusive breast fed babies in comparison to nonexclusive breast fed babies, but was significantly more in babies having birth weight >2.5 kg in comparison to those having birth weight of <2.5 kg. Other parameters of cognitive development were more or less same in both normal and LBW groups. Mental and motor development was same in both boys and girls. In behavior ratings, cooperation was significantly high (5.89 ± 2.54 vs. 4.71 ± 3.13, p=0.05) and vocalization (5.89 ± 1.07 vs. 4.58 ± 1.16) was also high, though not significant, in girls than boys.

Comparison of haematological values among different groups of low birth weight babies and normal birth weight babies.

This prospective cross sectional study was carried out in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. This study was undertaken to compare the haematological value (reference range) among Small for gestational age-low birth weight (SGA-LBW), Appropriate for gestational age-low birth weight (AGA-LBW) and Normal birth weight (NBW) babies. Total 90 (ninety) newborn babies were enrolled in this study. They were ultimately divided into three groups as a) Group I (SGA-LBW), b) Group II (AGA-LBW), c) Group III (NBW). Study period was one year (December 2003 to December 2004), Relevant informations were collected from the guardian of the babies before inclusion in the study. In group I, 19(63.3%) were preterm and 11(36.7%) were term. In group II, 30(100%) were preterm and in group III, 30(100%) were term. Mean Hb, and HCT levels were highest in group I (SGA-LBW) and the value was 17.14+/-1.41 gm/dl (Hb) and 0.51+/-0.04 (HCT) respectively. Mean Hb and HCT value were lowest in group II (AGA-LBW) and the value was 14.57+/-1.78 gm/dl (Hb) and 0.43+/-0.05 (HCT) respectively. In between value was found in group III (NBW) and the value was 16.14+/-1.09 gm/dl (Hb) and 0.48+/-0.04 (HCT) respectively. Differences were statistically significant. On the contrary, MCV Values were highest in group II (AGA-LBW) and the value was 103.23+/-4.99 (fl). Lowest MCV value was in group III (NBW) and the value was 98.13+/-3.93 (fl). In between result of MCV value was found in group I (SGA-LBW) and the value was 99.27+/-10.73 (fl). Differences were also statistically significant. MCH and MCHC level was also highest in group I (SGA-LBW). Difference was also statistically significant. No significant differences of TC of WBC and platelet counts were not found among different groups. Hb and HCT level had significant positive correlation with gestational age. Other parameters had no Positive correlation with gestational age.

Characterisation of Triticum vavilovii-derived stripe rust resistance using genetic, cytogenetic and molecular analyses and its marker-assisted selection.

Stripe rust resistance was identified in Triticum vavilovii( T. vaviloviiAus22498)-derived Russian wheat aphid (RWA)-resistant germplasm. Inheritance studies indicated monogenic control of resistance. The resistance gene was tentatively designated as Yrvav and was located on chromosome 1B by monosomic analysis. A close association (1.5+/-0.9% recombination) of Yrvav with a T. vavilovii-derived gliadin allele ( Gli-B1vav) placed it in chromosome arm 1BS. Yrvavwas allelic with Yr10. Tests with Yr10 avirulent and virulent pathotypes showed that Yrvav and Yr10 possess identical pathogenic specificity. Yrvav and Yr10 showed close genetic associations with alternate alleles at the Xpsp3000(microsatellite marker), Gli-B1 and Rg1 loci. Based on these observations Yrvav was named as Yr10vav. The close association between Xpsp3000 and Gli-B1 was also confirmed. The Yr10vav-linked Xpsp3000 allele (285 bp) was not present in 65 Australian cultivars, whereas seven Australian wheats lacking Yr10 carried the same Xpsp3000 allele (260 bp) as Yr10carrying wheat cultivar Moro. Xpsp3000 and/or Gli-B1 could be used in marker-assisted selection for pyramiding Yr10vavor Yr10 with other stripe rust resistance genes. Yr10vav was inherited independently of the T. vavilovii-derived RWA resistance.

How the health care system can improve mammography-screening rates for underserved women: a closer look at the health care delivery system.

The way care is delivered has dramatic impact on the patient-provider interaction and the outcomes experienced by the patient. This article explores a deceptively simple but very powerful method for evaluating and improving care delivery. Mammography is a routine screening procedure. However, many factors can influence how frequently women seek and obtain mammograms. Twenty-five low-income women identified empowering factors and barriers they experienced when trying to obtain a mammogram.

Aberrant expression of MSG1 transcriptional activator in human malignant melanoma in vivo.

MSG1 was originally isolated as a candidate pigmentation-related gene. MSG1 mRNA transcripts were expressed strongly in cultured human and mouse normal epidermal melanocytes, and in highly pigmented mouse melanoma cells, while its expression was very weak in cultured non-pigmented human melanoma cells. Thus, MSG1 was initially proposed to be a melanocyte-specific gene, and its possible role in pigmentation has been speculated. It was found recently that the MSG1 protein interacts functionally with Smad4, which plays a pivotal role in signal transduction of transforming growth factor-beta. In this study, we analyzed MSG1 protein expression by immunohistochemistry using human tumor samples from nevus and malignant melanoma to reveal its role in pigmentation and melanoma development in vivo. A relatively strong but heterogeneous expression of MSG1 protein was seen in melanomas compared with weak expression in nevi. In nevi, MSG1 expression was mostly confined to the pigmented region, while it was expressed in both pigmented and non-pigmented regions in melanoma. Intracellularly, MSG1 protein was localized in the cytoplasm of nevus cells, but was seen in both nuclei and cytoplasm of melanoma cells. These results support a hypothesis that MSG1 plays a role in pigmentation. It is also suggested that MSG1 may be involved in malignant transformation of pigment cells. Alternatively, the aberrant expression of MSG1 in melanoma cells might be due to the abnormal environment, including aberrant cytokine or growth factor expression, associated with melanoma formation.

Protective effect of topically applied olive oil against photocarcinogenesis following UVB exposure of mice.

Reactive oxygen species have been shown to play a role in ultraviolet light (UV)-induced skin carcinogenesis. Vitamin E and green tea polyphenols reduce experimental skin cancers in mice mainly because of their antioxidant properties. Since olive oil has also been reported to be a potent antioxidant, we examined its effect on UVB-induced skin carcinogenesis in hairless mice. Extra-virgin olive oil was applied topically before or after repeated exposure of mice to UVB. The onset of UVB-induced skin tumors was delayed in mice painted with olive oil compared with UVB control mice. However, with increasing numbers of UVB exposures, differences in the mean number of tumors between UVB control mice and mice pretreated with olive oil before UVB exposure (pre-UVB group) were lost. In contrast, mice that received olive oil after UVB exposure (post-UVB group) showed significantly lower numbers of tumors per mouse than those in the UVB control group throughout the experimental period. The mean number of tumors per mouse in the UVB control, pre-UVB and post-UVB groups was 7.33, 6.69 and 2.64, respectively, in the first experiment, and 8.53, 9.53 and 3.36 in the second experiment. Camellia oil was also applied, using the same experimental protocol, but did not have a suppressive effect. Immunohistochemical analysis of DNA damage in the form of cyclobutane pyrimidine dimers (CPD), (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in samples taken 30 min after a single exposure of UVB showed no significant difference between UVB-irradiated control mice and the pre-UVB group. In the post-UVB group, there were lower levels of 8-OHdG in epidermal nuclei, but the formation of CPD and (6-4) photoproducts did not differ. Exposure of olive oil to UVB before application abrogated the protective effect on 8-OHdG formation. These results indicate that olive oil topically applied after UVB exposure can effectively reduce UVB-induced murine skin tumors, possibly via its antioxidant effects in reducing DNA damage by reactive oxygen species, and that the effective component may be labile to UVB.

Difficulty in reaching low-income women for screening mammography.

Low-income women have a high mortality from breast cancer. Yet, they participate in breast cancer early detection screening programs less than women in the general population. An intervention study to improve screening mammography rates of low-income women participating in Tennessee's TennCare program (state Medicaid and Medicare program) revealed significant barriers to reaching these women. Intervention methods included mail, telephone calls, and home visits. Results indicate that only 38 percent of the women could be contacted for a baseline survey. Reasons for noncontact included absence from home (39 percent), having moved (22 percent), refusal to participate (17 percent), having no physical domicile (15 percent), language barriers (4 percent), and miscellaneous other factors (4 percent). Women with telephones tended to have a relatively higher economic status and were more successfully reached than women without telephones. These findings provide useful insights for future program planning and research design.

Preventive effect of antioxidant on ultraviolet-induced skin cancer in mice.

Reactive oxygen species (ROS) have been shown to be responsible for inducing DNA damage after ultraviolet radiation (UV). Antioxidant, vitamin E and epigallocatechin gallate extracted from green tea, applied topically to the skin, delayed the onset of UV-induced skin cancer in mice. Since olive oil is reported to have a potent antioxidative effect in in vitro system, we asked whether, topical use of olive oil reduces the number and delays the onset of UV-induced skin cancer in mice. We found that super virgin olive oil painted immediately after UVB radiation significantly delayed the onset and reduced the number of skin cancer, but pretreatment of super virgin olive oil and pre- and/or post treatment by regular olive oil neither retarded nor reduced skin cancer formation in UV-irradiated mice. Further, 8-hydroxy-deoxyguanosine (8-OHdG) formation in mice epidermis was apparently reduced by super virgin olive oil painted immediately after UV radiation, although cyclobutane pyrimidine dimers and (6-4) photoproducts were not reduced by olive oil treatment. Our results suggest that daily topical use of super virgin olive oil after sun bathing may delay and reduce UV-induced skin cancer development in human skin, possibly by decreasing ROS-induced 8-OHdG which is responsible for gene mutation.

Induced expression of p16 and p21 proteins in UVB-irradiated human epidermis and cultured keratinocytes.

It has been suggested that p16INK4a, the product of the cyclin-dependent kinase inhibitor 2 or multiple tumor suppressor 1 gene, prevents phosphorylation of the retinoblastoma gene product, and thus acts as a negative cell cycle regulator. To elucidate an effect of ultraviolet B (UVB) radiation on p16 expression and its relation to p21, and proliferating cell nuclear antigen (PCNA), immunohistochemical and western blot analyses were performed on UVB-irradiated normal human epidermis and cultured keratinocytes, respectively. Little p16 protein was seen in the control epidermis or keratinocytes. Increases in the levels of p16 protein in both UVB-irradiated epidermis and keratinocytes occurred in a similar manner, in which p16 was induced at 24-48 h and peaked at 72-120 h after irradiation. The induced expression of p21 was observed relatively earlier than that of p16, with peaked expression at 24-48 h and a return to control level by 168 h. PCNA expression was increased slightly until 48 h but significantly increased during 48-168 h of post-irradiation with peak expression at 72 h. These results indicate that together with p21, p16 protein may play an important role for protective or adaptive response to UVB exposure of human skin.

The inhibitory effect of DL-alpha-tocopheryl ferulate in lecithin on melanogenesis.

Oral vitamin E (alpha-tocopherol) supplementation has been reported to improve facial hyperpigmentation. The compound of alpha-tocopherol and ferulic acid, also an antioxidant connected with an ester bond, alpha-tocopheryl ferulate (alpha-TF) can absorb ultraviolet (UV) radiation and thus maintain tocopherol in a stable state. Our aim was to determine whether alpha-TF can be applied to improve and prevent facial hyperpigmentation induced by UV as a whitening agent as well as an antioxidant. In this study, the effects of alpha-TF on melanogenesis were examined using cultured human melanoma cells and normal human melanocytes in vitro. alpha-TF solubilized in 0.5% lecithin inhibited melanization significantly at the concentration of 30 micrograms/ml compared with arbutin (100 micrograms/ml), kojic acid (100 micrograms/ml), ascorbic acid (600 micrograms/ml), and tranexamic acid (600 micrograms/ml). alpha-TF had no effect on the protein amounts of tyrosinase, TRP (tyrosinase related protein)-1, and TRP-2 of human melanoma cells exposed to UV radiation, but inhibited tyrosine hydroxylase activity. alpha-TF neither directly inhibited tyrosinase activity of the large granule fraction extracted from melanoma cells, nor modulated glycosylation of tyrosinase. These results suggest that alpha-TF may be a candidate for whitening agent which suppresses melanogenesis, possibly by inhibiting tyrosine hydroxylase activity in an indirect manner. Further, alpha-TF decreased the amount of 8-hydroxydeoxyguanosine produced indirectly through active oxygen species (AOS) in guinea pig skin exposed to 2 times the minimal erythema dose of UVB radiation, but did not suppress the direct formation of cyclobutane pyrimidine dimers and (6-4) photoproducts. Thus alpha-TF may reduce AOS-induced DNA damage and thereby contribute at least in part to suppressing or retarding skin cancer development.

High levels of 8-hydroxy-2'-deoxyguanosine appear in normal human epidermis after a single dose of ultraviolet radiation.

Major photoproducts induced by carcinogenic ultraviolet (UV) radiation are the cylobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4 PPs). 8-Hydroxy-2 -deoxyguanosine (8-OHdG) is also a DNA base-modified product generated by reactive oxygen species in conditions of ultraviolet stress, Although UVB-induced CPDs and 6-4 PPs have been investigated in animal and human skin, little is known about the role of 8-OHdG in UVB-induced human skin damage or carcinogenesis. Normal human skin from three volunteers was exposed to UV radiation, and the time course of induction and removal of 8-OHdG was examined by immunohistochemical analysis with catalysed signal amplification on formalin-fixed paraffin sections. Formation of CPDs and 6-4 PPs was also examined by immunostaining on the same skin specimens. Control epidermis with no exposure to UV radiation showed little nuclear staining of 8-OHdG, but an increased level of 8-OHdG was clearly observed in epidermis biopsied after irradiation. Induced 8-OHdG can rapidly be removed from nucleus during the first 24-48 h, as the staining intensity diminished gradually, almost reaching the control level by 72-96 h after irradiation. Staining for CPDs or 6-4 PPs revealed induction of these photoproducts in human skin, although 6-4 PP-positive cells disappeared more rapidly than those that stained for CPDs or 8-OHdG. Together with protective effect of antioxidants, our results indicate that not only CPDs and 6-4 PPs but also 8-OHdG may play a significant part in UV carcinogenesis.

Regulation of expression of MSG1 melanocyte-specific nuclear protein in human melanocytes and melanoma cells.

MSG1 is a nuclear protein and a possible transcriptional transactivator that is expressed strongly in melanocytes but very weakly, if at all, in most nonmelanocytic cells or adult mouse tissues. This strong expression of MSG1 in cultured normal human epidermal melanocytes was found to be dependent on both endothelin-1 and FGF-2. The phorbol ester TPA could be substituted for endothelin-1. The MSG1 mRNA transcripts were rapidly induced by either endothelin-1 or TPA. However, FGF-2 had no effects at the mRNA level, suggesting its contribution at the translational and/or posttranslational level(s). MSG1 (as well as its mRNA transcripts) was induced by TPA in human melanoma cells, which produce FGF-2 as an autocrine growth factor. Melanoma cells derived from primary tumors or tyrosinase-positive metastatic melanoma cells expressed MSG1 after TPA treatment, while tyrosinase-negative metastatic melanoma cells or nonmelanocytic cells did not. This TPA-induced MSG1 expression in melanoma cells correlated with the expression of the MSG1 mRNA transcripts and TPA-dependent transcriptional activation of the MSG1 promoter sequence, indicating its transcriptional regulation. In vivo, MSG1 protein was detected in human nevocytic nevus confined to the pigmented region, while MSG1 expression showed cell-level heterogeneity in pigmented melanoma tissues. These results demonstrate that MSG1 expression is regulated transcriptionally and posttranscriptionally by local growth factors as well as by the cellular status of differentiation.

Expression of fibroblast growth factor receptors in naevus-cell naevus and malignant melanoma.

In a previous study, we showed by immunohistochemical analysis that basic fibroblast growth factor (bFGF) is expressed strongly and homogeneously in naevus-cell naevus (NCN), while that in malignant melanoma (MM) is heterogeneous and sometimes non-existent. In order to elucidate the role of bFGF in these pigmented tumours, the expression of its receptors must be determined. In this study, we performed an immunohistochemical analysis of FGF receptors 1, 2 and 3 (FGFR-1, FGFR-2 and FGFR-3, respectively) in NCN and MM and compared their expression and localization with those of bFGF. The expression of bFGF and its three receptors was also examined in melanoma cell lines. None of the 10 NCN that showed strong, homogeneous staining for bFGF expressed FGFR-1 or FGFR-3 proteins; six weakly expressed FGFR-2 protein. Ten primary and 10 metastatic MM showed heterogeneous expression for the three receptors, with larger populations of FGFR-3-negative cells in the primary than in the metastatic tumours. Western blot analysis showed homogeneous expression of bFGF protein in all four melanoma cell lines tested, while FGFR proteins had a heterogeneous distribution in the different cell lines. Cultured NCN and normal melanocytes showed no immunoreactive band for FGFR-1 protein, the only protein tested. Our results suggested that tumour-derived bFGF is involved in melanoma formation through an autocrine mechanism, but is involved mostly through a paracrine or other mechanisms in NCN.

Increased level of c-erbB-2/neu/HER-2 protein in cutaneous squamous cell carcinoma.

Overexpression of c-erbB-2/neu/HER-2 oncoprotein, a receptor tyrosine kinase, has been demonstrated in a variety of human cancers. To elucidate the involvement of c-erbB-2 in human skin carcinogenesis, we examined expression of the protein in skin samples from five cases of keratoacanthoma (KA), 10 of actinic keratosis (AK), 24 of squamous cell carcinoma (SCC) and 10 of basal cell carcinoma (BCC) and five samples of normal epidermis, using an immunohistochemical method on formalin-fixed, paraffin-embedded sections. Expression of c-erbB-2 was also examined in cultured SCC cell lines, a premalignant cell line and in cultured normal keratinocytes. Normal epidermal cells showed no or very little c-erbB-2 protein, but the covering epidermal layer of some tumours showed a few strongly positive cells. Samples of KA and AK showed barely detectable c-erbB-2 protein in only a few cases. Twenty of the 24 cases of SCC had elevated expression of c-erbB-2 protein, with a tendency to more positive cells in metastatic lesions. Five of the 10 cases of BCC stained for c-erbB-2 but more weakly than those of SCC. Reaction products of the positive cells were seen in the cytoplasm. All three cultured SCC cell lines stained for c-erbB-2 protein more strongly than the premalignant HaCaT or normal keratinocytes. Our results indicate the possible involvement of c-erbB-2 overexpression in the malignant conversion of keratinocytes.

p21WAF1/CIP1 expression in non-melanoma skin tumors.

Abnormal control of the cell cycle is closely linked to carcinogenesis. p21WAF1/CIP1 protein is a universal inhibitor of G1 cyclin-dependent kinase and is induced by p53-dependent and -independent pathways. In order to elucidate the role of p21WAF1/CIP1 in human skin carcinogenesis, protein expression in squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), actinic keratosis (AK), keratoacanthoma (KA), seborrheic keratosis (SK), and normal skin was examined using an immunohistochemical method. In normal skin, a few positive cells were seen in some cases in the upper spinous layer of the epidermis; sebaceous glands also had positive cells. In cases of SK and KA, positive cells were found in the basal and suprabasal epidermal layers (proliferation pattern), and in cases of BD and AK, positive cells were seen mainly in the upper spinous layer (differentiation pattern). Cases of SCC had more positive cells and showed two staining patterns: proliferation, or mixed. Cases of BCC had no positive cells. p21WAF1/CIP1 has some unidentified role in keratinocyte tumorigenesis, which may not be related directly to carcinogenesis.

The expression of retinoblastoma protein in epidermis is induced by ultraviolet B exposure.

DNA damage induced by ultraviolet light (UV) can be repaired while cells are arrested in the cell cycle. Tumour suppressor gene p53 has been implicated as being involved in the G1 arrest after UV irradiation. Normal human skin from three volunteers was exposed to UVB and the expression of p53, Ki-67 and retinoblastoma gene product (pRb) was examined immunohistochemically, in addition to observation for sunburn cells. p53 protein started to be expressed at 6 h after UVB irradiation. It peaked at 12-48 h. Ki-67 expression was induced after 48 or 72 h of irradiation. pRb begun to be expressed at 24 or 48 h and peaked at 48-96 h. p53-positive cells were distributed throughout the epidermis, while Ki-67 and pRb positive cells were seen mainly at the lower epidermis. Finally, sunburn cells, which are presumably apoptotic cells, appeared at 24 h and peaked at 24-48 h and were seen at upper epidermis. The different and co-ordinated expression, although variable between individuals, indicates important roles for p53 and pRb on the maintenance of the homeostasis of the epidermis after UV irradiation.