Disparities in Obesity, Physical Activity Rates, and Breast Cancer Survival.

The significantly higher breast cancer (BCa) mortality rates of African-American (AA) women compared to non-Hispanic (NHW) white women constitute a major US health disparity. Investigations have primarily focused on biological differences in tumors to explain more aggressive forms of BCa in AA women. The biology of tumors cannot be modified, yet lifestyle changes can mitigate their progression and recurrence. AA communities have higher percentages of obesity than NHWs and exhibit inefficient access to care, low socioeconomic status, and reduced education levels. Such factors are associated with limited healthy food options and sedentary activity. AA women have the highest prevalence of obesity than any other racial/ethnic/gender group in the United States. The social ecological model (SEM) is a conceptual framework on which interventions could be developed to reduce obesity. The SEM includes intrapersonal factors, interpersonal factors, organizational relationships, and community/institutional policies that are more effective in behavior modification than isolation from the participants' environmental context. Implementation of SEM-based interventions in AA communities could positively modify lifestyle behaviors, which could also serve as a powerful tool in reducing risk of BCa, BCa progression, and BCa recurrence in populations of AA women.

Plasma 5-S-cysteinyldopa differentiates patients with primary and metastatic melanoma from patients with dysplastic nevus syndrome and normal subjects.

To determine whether plasma 5-S-cysteinyldopa levels are useful in following up patients at risk for melanoma, we measured plasma 5-S-cysteinyldopa in patients with dysplastic nevus syndrome and/or malignant melanoma and in control subjects. In patients with dysplastic nevus syndrome, plasma 5-S-cysteinyldopa levels did not differ from those in control subjects. Conversely, patients with malignant melanomas had significantly higher plasma 5-S-cysteinyldopa levels than did controls. Those with localized cutaneous malignant melanoma and no distant metastases (Stage I and II disease) had 5-S-cysteinyldopa levels twofold greater than those of control subjects, whereas the levels of those with regional lymph node involvement (Stage III disease) were fourfold greater than those of control subjects. Levels of those with extraregional metastases (Stage IV disease) were 7- to 450-fold higher than those of control subjects. Moreover, plasma 5-S-cysteinyldopa levels correlated with the spread of disease and were useful in distinguishing primary melanoma and Stages III and IV melanoma. We conclude that plasma 5-S-cysteinyldopa may be an important tool for identifying melanoma at an earlier, more curable stage and for following up patients at risk for the development of melanoma, for example, those with dysplastic nervus syndrome.

Plasma 5-S-cysteinyldopa correlates with tumor size in melanoma-bearing mice.

A sensitive assay method employing high performance liquid chromatography with electrochemical detection (HPLC-ED) was used to compare 5-S-cysteinyldopa (CD) levels in plasma to tumor size in a murine melanoma model system. Plasma CD levels correlated with the sizes of primary tumor masses in mice, and the presence of metastatic tumors did not significantly affect the relationship. Elevated plasma CD levels appear to be directly related to tumor pigmentation: mice who had nonpigmented tumors induced by injections of amelanotic melanoma cells (NP) did not have elevated plasma CD levels. These studies indicate that plasma CD levels may serve as a marker for pigmented malignant melanomas and may be useful in following patients who are at high risk for these tumors.

Glucagonoma syndrome: in vitro evidence that glucagon increases epidermal arachidonic acid.

A 63-year-old white woman with perioral dermatitis, a sore tongue, and an erythematous dermatosis in the inframammary and perineal regions underwent surgical removal of a pancreatic glucagonoma. The patient's plasma and pooled normal human plasma containing Sigma glucagon were fed to human keratinocyte cultures and increased arachidonic acid levels by 300% and 200%, respectively, when compared to pooled normal human plasma with no added commercial glucagon. These experiments suggest that glucagon may increase inflammatory mediators such as arachidonic acid and its metabolites in the epidermis, causing the skin lesions seen in the glucagonoma syndrome.

Lentiginosis associated with a left atrial myxoma.

A 14-year-old white male patient with lentiginosis was in congestive heart failure. He was noted to be redheaded, and the lentigines were especially concentrated on the face, including the lips. A two-dimensional echocardiogram revealed an orange-sized mobile mass in the left atrium. Cardiac surgery for removal of the left atrial myxoma was successful, and a complete recovery was made. This is the second report of lentiginosis associated with a left atrial myxoma and the first in which the immediate family did not have similar pigmentary changes. Lentiginosis and associated cardiac manifestations are briefly reviewed.

Keratolinin: the soluble substrate of epidermal transglutaminase from human and bovine tissue.

Substrates of human and bovine epidermal transglutaminase (glutaminyl-peptide gamma-glutamyltransferase, R-glutaminyl-peptide:amine-gamma-glutamyltransferase, EC 2.3.2.13) were isolated and purified by ion exchange chromatography and preparative zone electrophoresis. These substrates of Mr 36,000, which we propose to call keratolinin, incorporated dansylcadaverine and were precipitated by antibody. Keratolinin is ultimately polymerized on the inner leaflet of the keratinocyte membrane to form the cornified envelope. Each Mr 36,000 substrate was dissociated by chaotropic agents or detergents into noncovalent subunits; the Mr of these subunits was 6,000-6,200 on electrophoresis in 15% acrylamide/1% NaDodSO4/6 M urea gels. Isoelectric focusing of human or bovine keratolinin revealed two moieties separated by 0.3-0.4 pH unit (human, 5.4/5.0; bovine, 6.3/6.0). The two proteins were readily resolved by chromatofocusing and each isoelectric moiety of bovine keratolinin incorporated dansylcadaverine by epidermal transglutaminase and calcium and reacted with identity to antiserum to soluble Mr 36,000 keratolinin. Antiserum to human keratolinin failed to crossreact with its bovine counterpart. Antiserum to involucrin did not crossreact with either keratolinin or epidermis by immunodiffusion. Human and bovine epidermal keratolinins are biochemically similar but immunochemically distinct proteins from the epidermis. Involucrin appears only in significant quantities in cell culture.

Biochemistry of transglutaminases and cross-linking in the skin.

Transglutaminase is a calcium-dependent enzyme found widely in nature. It catalyzes the formation of epsilon-(gamma-glutamyl)lysine bonds that participate in processes varying from fibrin clot formation to epidermal cell envelope formation. Epidermal transglutaminase is localized to the granular layer of the epidermis. It catalyzes the covalent cross-linking of a soluble cytoplasmic substrate into large polymers to form the cornified envelope that lines the inner membrane of keratinocytes in the stratum corneum. The soluble precursor from epidermis has been named keratolinin, and from keratinocyte culture, it has been named involucrin. Hair follicle transglutaminase is biochemically and immunochemically distinct from its epidermal counterpart. It has been localized to the inner root sheath and medulla of the hair follicle. The substrate of hair follicle transglutaminase has been poorly defined but appears to be rich in the amino acid citrulline. Transglutaminase has been shown to be an important marker of normal differentiation. There is a rise in its activity at the time of keratinization, and transglutaminase activity has been shown to be greatly decreased in basal cell epithelioma and in psoriasis. Keratinocyte cell culture has proven most helpful in delineating the processes of normal differentiation and keratinization, since the formation of the cell envelope in culture appears to parallel the formation in vivo.

In vitro and in vivo inhibition of [3H]imipramine binding by cadmium.

Chronic exposure of rats to CdCl2 altered the specific binding of [3H]imipramine to membranes from platelets and hypothalamus. There was a decrease in Bmax of 10-40% and a decrease in KD values of 30-40% as compared to the control group. In vitro studies on the inhibition of [ 3H ]imipramine binding to membranes from human and rat platelets and hypothalamus by CdCl2 corroborate the in vivo results which imply that the imipramine binding protein contains Cd2+-sensitive groups.