To the Editor: As of 2019 National Cancer Institute data show that melanoma is the fifth most common cancer in the United States.1National Cancer InstituteCancer Stat Facts: melanoma of the skin. SEER.https://seer.cancer.gov/statfacts/html/melan.htmlDate accessed: April 28, 2021Google Scholar There has been a recent push to include the histopathologic subtype of nodular melanoma as an independent prognostic classifier due to the identification of associated aggressive histopathologic characteristics and shorter recurrence-free times.2Lattanzi M. Lee Y. Simpson D. et al.Primary melanoma histologic subtype: impact on survival and response to therapy.J Natl Cancer Inst. 2019; 111: 180-188Crossref PubMed Scopus (34) Google Scholar,3Dessinioti C. Dimou N. Geller A.C. et al.Distinct clinicopathological and prognostic features of thin nodular primary melanomas: an international study from 17 centers.J Natl Cancer Inst. 2019; 111: 1314-1322Crossref PubMed Scopus (17) Google Scholar We used the population-based, Genes, Environment, and Melanoma (GEM) study,4Begg C.B. Hummer A.J. Mujumdar U. et al.A design for cancer case-control studies using only incident cases: experience with the GEM study of melanoma.Int J Epidemiol. 2006; 35: 756-764Crossref PubMed Scopus (60) Google Scholar to assess the levels of agreement between community pathologists, those who originally diagnosed the melanoma, and expert study dermatopathologists, who reviewed the lesion for complete histology, histopathologic subtype, and Breslow thickness. The salient components of the GEM study were that it was population-based, multi-country size, and included disease-specific mortality data and re-review of hematoxylin-eosin–stained tissues by dermatopathologists. We evaluated how histopathologic subtype misclassification might impact the reported disease-specific mortality. Our study included 1957 individuals with a first primary melanoma diagnosed in the year 2000, at centers of the GEM study in Australia, Canada, Italy, and the United States. The Institutional Review Board approval was obtained, and the subjects signed written consent. Each patient had their hematoxylin-eosin–stained slides read initially by a community pathologist, who reported Breslow thickness and histopathologic subtype followed by an independent review by a dermatopathologist, blinded to the community pathologist report. The vital status was obtained at an average of 7.4 years. Within the study population and lethal melanoma cases, descriptive statistics were calculated and the frequency tables that compared the kappa value for the readings of community pathologists and dermatopathologists were created for Breslow thickness and histopathologic subtype. All the tests were two-sided and P < .05 was considered significant. The data were analyzed using SAS 9.4 software and the interobserver variability was calculated with Fleiss' method.5Fleiss J.L. Levin B. Paik M.C. Statistical Methods for Rates and Proportions.3rd ed. John Wiley & Sons, Inc., 2003Crossref Google Scholar The mean age of the subjects at diagnosis was 55 years and 48.5% of them were women. The kappa for Breslow thickness was 0.72 (95% CI, 0.69-0.75), demonstrating a "substantial agreement." The kappa within lethal cases was 0.56 (95% CI, 0.45-0.66), suggesting a "moderate agreement." The overall kappa for the histopathologic subtype of 0.27 demonstrates only a "fair agreement" (Table I), whereas that for the reviewing dermatopathologists was 0.68, indicating a "substantial agreement." The kappa for nodular subtype had only 51.3% agreement. Within the lethal cases, the kappa value was "fair," 0.30 (Table II).Table IConcordance of histopathologic subtype between community pathologists and dermatopathologistsDermatopathologistsCommunity pathologistsSSMNMLMMALMSCNOSOtherTotalSSM919†Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed.337033523NM5596†Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed.712183LMM55472†Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed.1044ALM3113†Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed.100SC82001†Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed.23NOS35450462249†Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed.15Other1100100†Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed.Total (percent agreement)1395 (65.8)187 (51.3)196 (36.7)10 (0.30)10 (0.10)125 (39.2)28 (0.0)1951∗6 missing values.†Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed.Overall Correlation = 0.27 (95% CI, 0.24-0.30).ALM, Acral lentiginous melanoma; LMM, lentigo maligna melanoma; NM, nodular melanoma; NOS, not otherwise specified; SC, spindle cell; SSM, superficial spreading melanoma.∗ 6 missing values.† Numbers in bold represent the number of subjects for which community pathologists and dermatopathologists agreed. Open table in a new tab Table IIDeaths per histopathologic subtypeDermatopathologistsCommunity pathologistsSSMNMLMMALMSCNOSOtherTotalSSM34∗Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed.702130NM1222∗Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed.21051LMM422∗Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed.0001ALM1000∗Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed.000SC01000∗Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed.02NOS982109∗Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed.1Other0100100∗Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed.Total (percent agreement)60 (56.7)41 (53.7)6 (33.3)4 (0.0)2 (0.0)17 (52.9)5 (0.0)135∗Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed.Overall Correlation = 0.30, (95% CI, 0.19-0.40).ALM, Acral lentiginous melanoma; LMM, lentigo maligna melanoma; NM, nodular melanoma; NOS, not otherwise specified; SC, spindle cell; SSM, superficial spreading melanoma.∗ Numbers in bold represent the number of cases where community pathologists and dermatopathologists agreed. Open table in a new tab Overall Correlation = 0.27 (95% CI, 0.24-0.30). ALM, Acral lentiginous melanoma; LMM, lentigo maligna melanoma; NM, nodular melanoma; NOS, not otherwise specified; SC, spindle cell; SSM, superficial spreading melanoma. Overall Correlation = 0.30, (95% CI, 0.19-0.40). ALM, Acral lentiginous melanoma; LMM, lentigo maligna melanoma; NM, nodular melanoma; NOS, not otherwise specified; SC, spindle cell; SSM, superficial spreading melanoma. Our study illustrated a moderate-to-substantial agreement on Breslow thickness between the community pathologists and dermatopathologists. The decrease in Breslow-related kappa in fatal cases may represent less precision in measuring thicker tumors as lethal tumors tended to be deeper. We also observed higher rates of disagreement among pathologists for the histopathologic subtype. Considering that the subtype can indicate tumor characteristics, any misclassification might influence patients' counseling, treatment options, and their disease perception. The limitations of our study were that only the Breslow thickness and histopathologic subtype were measured due to the limited initial reporting by community pathologists and that the slide reviewed by the community pathologist may differ from the same slide reviewed by the dermatopathologist. Based on these results, we propose the judicious interpretation of nodular melanoma as a prognostic factor. The data on subtype without expert dermatopathology review should be used with caution until the interrater concordance improves. The patient prognosis should continue to be based on more reproducible characteristics such as Breslow thickness, ulceration, mitotic index, and metastasis. None disclosed. GEM Study Group: Coordinating Center, Memorial Sloan Kettering Cancer Center, New York, New York, Marianne Berwick (PI, currently at the University of New Mexico, Albuquerque, NM), Colin Begg, PhD (co-PI), Irene Orlow, PhD, MS (coinvestigator), Klaus J. Busam, MD (Dermatopathologist), Isidora Autuori, MS (Laboratory Member), Pampa Roy, PhD (Senior Laboratory Technician), Anne Reiner, MS (Biostatistician), University of New Mexico, Albuquerque, NM, Marianne Berwick, MPH, PhD (PI), Li Luo, PhD (Biostatistician), Tawny W. Boyce, MPH (Data Manager). Study Centers: The University of Sydney and The Cancer Council New South Wales, Sydney, Australia: Anne E. Cust, PhD (PI), Bruce K. Armstrong MD, PhD (former PI), Anne Kricker PhD, (former co-PI); Menzies Institute for Medical Research University of Tasmania, Hobart, Australia: Alison Venn (current PI), Terence Dwyer (PI, currently at University of Oxford, United Kingdom), Paul Tucker (Dermatopathologist); BC Cancer Vancouver, Canada: Richard P. Gallagher, M.A. (PI), Cancer Care Ontario, Toronto, Canada: Loraine D. Marrett, PhD (PI), Lynn From, MD (Dermatopathologist); CPO, Center for Cancer Prevention, Torino, Italy: Roberto Zanetti, MD (PI), Stefano Rosso, MD, MSc (co-PI); Lidia Sacchetto, PhD, (Biostatistician); University of California, Irvine, California: Hoda Anton-Culver, PhD (PI); University of Michigan, Ann Arbor, Michigan: Stephen B. Gruber, MD, MPH, PhD (PI, currently at City of Hope National Medical Center, California), Joseph D. Bonner, PhD (coinvestigator, joint at City of Hope-University of Michigan); University of North Carolina, Chapel Hill, North Carolina: Nancy E. Thomas, MD, PhD (PI), Kathleen Conway, PhD (coinvestigator), David W. Ollila, MD (coinvestigator), Pamela A. Groben, MD (Dermatopathologist), Sharon N. Edmiston, BA (Research Analyst), Honglin Hao (Laboratory Specialist), Eloise Parrish, MSPH (Laboratory Specialist), Jill S. Frank, MS (Research Assistant), David C. Gibbs, BS (Research Assistant, currently MD/PhD candidate at Emory University, Atlanta, Georgia); University of Pennsylvania, Philadelphia, Pennsylvania: Timothy R. Rebbeck, PD (former PI), Peter A. Kanetsky, MPH, PhD (PI, currently at Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute.); UV data consultants: Julia Lee Taylor, PhD, and Sasha Madronich, PhD, National Centre for Atmospheric Research, Boulder, Colorado.
CD36 is a multifunctional cell-surface receptor that binds adhesion molecules such as thrombospondin-1 and collagen and modified lipids and/or lipoproteins. It participates in cellular uptake of photoreceptor outer segments and scavenging of apoptotic cells and oxidized low density lipoprotein (Ox-LDL). Recognition and internalization of Ox-LDL by mononuclear phagocytes may play an important role in the development of atherosclerotic lesions. We have utilized a series of recombinant bacterial glutathioneS-transferase/CD36 fusion proteins that span nearly all of the CD36 molecule to characterize the structural domain on CD36 that recognizes Ox-LDL. We found that the Ox-LDL-binding domain is different from the thrombospondin-1-binding domain located at amino acids 93–120. A fusion protein containing the region extending from amino acids 5 to 143 formed specific, saturable, and reversible complexes with Ox-LDL. As with intact CD36, binding was blocked by excess unlabeled Ox-LDL and antibodies to CD36. The stoichiometry and affinity of the fusion protein for Ox-LDL were similar to those of the intact protein. We also demonstrated that this fusion protein competitively inhibited binding of Ox-LDL to purified platelet CD36 and to CD36 expressed on peripheral blood monocytes and CD36 cDNA-transfected melanoma cells. The use of smaller peptides and fusion proteins including those spanning amino acids 28–93 and 5–93 has further narrowed the binding site to a region from amino acids 28 to 93, although participation of a sequence in the noncontiguous region 120–155 cannot be excluded. This study, for the first time, demonstrates unique regions of the scavenger receptor CD36 that bind the Ox-LDL ligand. Our structural analysis of the receptor provides information as to potential control of the trafficking of modified lipoproteins into the blood vessel wall.
Background Mannose-binding Allium sativum leaf agglutinin (ASAL) is highly antinutritional and toxic to various phloem-feeding hemipteran insects. ASAL has been expressed in a number of agriculturally important crops to develop resistance against those insects. Awareness of the safety aspect of ASAL is absolutely essential for developing ASAL transgenic plants. Methodology/Principal Findings Following the guidelines framed by the Food and Agriculture Organization/World Health Organization, the source of the gene, its sequence homology with potent allergens, clinical tests on mammalian systems, and the pepsin resistance and thermostability of the protein were considered to address the issue. No significant homology to the ASAL sequence was detected when compared to known allergenic proteins. The ELISA of blood sera collected from known allergy patients also failed to show significant evidence of cross-reactivity. In vitro and in vivo assays both indicated the digestibility of ASAL in the presence of pepsin in a minimum time period. Conclusions/Significance With these experiments, we concluded that ASAL does not possess any apparent features of an allergen. This is the first report regarding the monitoring of the allergenicity of any mannose-binding monocot lectin having insecticidal efficacy against hemipteran insects.
OBJECTIVE:The present study was to find out effect of maternal body mass index (BMI) on obstetric behaviour and pregnancy outcome.METHOD: This was a hospital-based observational study ,based on 636 primigravid women delivering singleton live baby in May 2012 to June 2013 .We categorise the women into three groups .Obstetric and perinatal outcome were compared among three groups underweight (BMI<18.5kg/m2),normal(18.5-24.9kg/m2)and obese(BMI>25 kg/m2).RESULTS: Obese women were more prone to adverse maternal and perinatal outcome such as prolong pregnancy, gestational diabetes mellitus, preeclampsia, intrauterine growth restriction, operative vaginal delivery ,shoulder dystocia, induction of labour, caesarean section, post partum haemorrhage, puerperal pyrexia, low birth weight baby, preterm baby, post maturity, macrosomia and low Apgar score and no significance difference were found regarding anaemia in pregnancy, premature rupture of membrane comparing normal BMI pregnant mother.Underweight pregnant mother were more prone to develop anaemia in pregnancy, intrauterine growth restriction, premature rupture of membrane, post partum haemorrhage, puerperal pyrexia, low birth weight baby, preterm baby and low Apgar score compare to normal BMI pregnant mother.CONCLUSION: Both overweight and underweight are the definite risk factor for adverse maternal and perinatal outcome .This may be due to altered metabolic state in those cases.
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)