Online prediction tools for melanoma survival: A comparison.

BACKGROUND: Breslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that accurately considers these and other predictors could be valuable for clinicians managing melanoma patients. OBJECTIVE: To compare online melanoma survival prediction tools that request user input on clinical and pathological features. METHODS: Search engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared. RESULTS: Three tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival. LIMITATIONS: The authors did not have access to the base data used to compile various prediction tools. CONCLUSION: The LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects.

Merkel cell carcinoma update: the case for two tumours.

Merkel cell carcinoma (MCC) is an aggressive tumour with neuroendocrine differentiation. Clinically significant differences within the entity we know as MCC are apparent. This review aims to evaluate the evidence for differences in tumours within Merkel cell carcinoma and to stratify these. A literature search of research pertaining to various characteristics MCC was undertaken from 1972, when Merkel cell carcinoma was first described, to 2018, using PubMed and similar search engines. A total of 41 papers were analysed, including clinical trials, laboratory-based research and reviews. A proportion of MCC has Merkel cell polyomavirus genome integrated (MCPyV+) while others do not (MCPyV-). Both types have a different mutation burden. MCPyV+ tumours are likely true neuroendocrine carcinomas, with a dermal origin, probably from fibroblasts which have been transformed by integration of the viral genome. MCPyV-tumours are likely derived from either keratinocytes or epidermal stem cells, are probably squamous cell carcinomas with neuroendocrine differentiation, and are related to sun damage. Prognostic factors (apart from tumour stage) include the MCPyV status, with MCPyV+ tumours having a better prognosis. P63 expression confers a worse prognosis in most studies. CD8+ lymphocytes play an important role, providing a possible target for PD1/PD-L1 blockade treatment. The incidence of MCC varies from country to country. Countries such as Australia have a high rate and a far greater proportion of MCPyV- tumours than places such as the United Kingdom. MCC doubtlessly encompasses two tumours. The two tumours have demonstrated differences in prognosis and management. One is a neuroendocrine carcinoma related to MCPyV integration likely derived from fibroblasts, and the other is a UV-related squamous cell carcinoma with neuroendocrine differentiation, presumptively derived from either keratinocytes or epidermal stem cells. We propose naming the former Merkel type sarcoma and the latter squamous cell carcinoma, Merkel type.

Purification and characterization of gamma-glutamyltransferase from rat pancreas.

gamma-Glutamyltransferase ((5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2.) from rat pancreas has been purified to homogeneity and shown to be a glycoprotein of apparent molecular weight 68000, composed of one heavy and one light subunit, with respective molecular weights 43000 and 25000. At the optimum pH 8.0 the specific activity of the purified enzyme is 630 units/mg protein, with L-gamma-glutamyl-p-nitroanilide as substrate (Km = 0.9 mM) and 20 mM glycylglycine as acceptor. The enzyme is inactivated by the active-site modifying agent and glutamine analogue, 6-diazo-5-oxo-L-norleucine, through a specific and stoichiometric reaction with the light subunit (Ki = 1.2 mM); both the inactivation and the modification of the light subunit are accelerated by maleate and prevented by S-methylglutathione. The enzyme is also inactivated by the fluorescent alkylating agent 5-iodoacetamidofluorescein, by specific and stoichiometric incorporation of the fluorescent moiety into the light subunit, which is likewise prevented by S-methylglutathione, but is unaffected by maleate. Antiserum to rat kidney gamma-glutamyltransferase cross-reacts with the pancreas enzyme in immunodiffusion and inhibits its activity in the p-nitroanilide assay. Despite structural, enzymological and immunological similarities between the pancreas and kidney enzymes, their amino acid compositions are markedly different. The rat pancreas enzyme shows an interesting ontological development, being present in minimal amounts in the fetus, and increasing dramatically on birth and during the following 2 days.

A comparison of the structure of hamster pancreatic insulin and insulin extracted from a transplantable hamster islet-cell carcinoma.

Insulin has been isolated from pancreases of the Syrian hamster and from a transplantable islet-cell tumor of the hamster. Acid/ethanol extraction, ether precipitation, ion exchange and gel filtration chromatography gave preparations of suitable purity for structural studies. Using trypsin cleavage, automatic Edman degradation and manual Edman degradation, a complete sequence of the pancreatic insulin B chain was determined. By automatic Edman degradation, the amino-terminal 10 residues of the pancreatic A chain were assigned and the sequence of carboxy-terminal eleven residues could be deduced by homology to other mammalian and avian insulins. The sequence assigned to hamster insulin A chain is identical to that of the rat, mouse and spiny mouse. The sequence of hamster insulin B chain is identical to rabbit and spiny mouse B chain. In terms of protein evolution, hamster insulin thus appears to occupy an intermediate position between rabbit and rat insulins. Amino acid composition, tryptic peptide composition and partial sequence analysis of the hamster tumor insulin showed no differences from hamster pancreatic insulin.

Crystallographic characterization of a Cu,Zn superoxide dismutase from Photobacterium leiognathi.

Crystals of a copper-zinc superoxide dismutase from Photobacterium leiognathi, a luminescent marine bacterium that is the species-specific symbiont of the ponyfish, have been obtained from 2-methyl-2,4-pentanediol solutions. The space group was determined using screenless small-angle precession photographs, and was confirmed by analyzing area detector diffraction data with the XENGEN programs for indexing and refinement. The crystals are monoclinic, space group C2 (a = 126.4 A, b = 87.0 A, c = 44.4 A, beta = 92.8 A), and have two 32,000 Mr dimers per asymmetric unit. The crystals diffract to at least 2.7 A resolution, are resistant to radiation damage, and are suitable for determination of the structure by X-ray diffraction.

Hemidesmosomes, collagen VII, and intermediate filaments in basal cell carcinoma.

We have undertaken an analysis of hemidesmosomes (HD) and their associated structures, intermediate filaments (IF) and anchoring fibrils (AF), in various types of basal cell carcinoma (BCC). Using a combination of electron microscopy and immunofluorescence microscopy we show that there is a correlation between the loss of HD and tumor type (i.e., in solid and infiltrative BCC hemidesmosomes are present, sometimes in reduced numbers), while there appears to be a lack of hemidesmosomes in cells of sclerosing specimens. Moreover, even though there is a loss of cytoplasmic constituents of the HD in sclerosing forms of BCC, this is not the case with regard to collagen VII, a component of AF, which are normally associated with the extracellular side of the HD. Collagen VII is localized to the basement membrane zone of tumor cells in the absence of the cytoplasmic constituents of HD. Furthermore, deposits of collagen VII occur in the connective tissue close to tumor cell populations in all but one of the BCC specimens we analyzed. In addition to modifications in HD and AF in BCC tissue, there are changes in the cytoskeletal elements of both tumor cells and the normal appearing epidermis that overlies tumor areas. In sclerosing BCC microfilaments are commonly observed along the basal portions of tumor cells where they abut the connective tissue. IF are often found interacting with these microfilaments. Indirect immunofluorescence analysis of tumor tissue using a monoclonal keratin antibody preparation, AE1, which in normal epidermis stains basal cells, reveals that AE1 antibodies only weakly stain tumor cells. Moreover, in the epidermis that overlies tumor cell regions AE1 antibodies stain suprabasal cells and not basal cells. This change in staining pattern generated by AE1 antibodies appears to depend upon the proximity of tumor cells. These results are discussed in relation to the organization of the HD and its associated AF and IF. The possibility that HD, IF, and AF antibody preparations may be of diagnostic use is raised.

Water-induced itching without cutaneous signs. Aquagenic pruritus.

Aquagenic pruritus is now a well-recognized symptom complex, usually of unknown origin. A few prove to have polycythemia rubra vera. We describe an important and distinct subset, termed aquagenic pruritus of the elderly, in which old age, dry skin, and seasonal weather conditions are major factors. Unlike other varieties, aquagenic pruritus of the elderly responds to appropriate local measures.

Inflammatory linear verrucous epidermal nevus. Epidermal protein analysis in four patients.

Inflammatory linear verrucous epidermal nevus (ILVEN) may be difficult to differentiate clinically from psoriasis. We report four cases of ILVEN that confirm the observation that the analysis of epidermal proteins by sodium lauryl sulfate-polyacrylamide gel electrophoresis (SLS-PAGE) discloses a pattern different from that seen in psoriasis. We have also found, however, that the SLS-PAGE epidermal protein pattern is not identical in each case of ILVEN.

Changes in cochlear antioxidant enzyme activity after sound conditioning and noise exposure in the chinchilla.

Exposure to low level noise prior to a high level exposure reduces noise-induced hearing loss in mammals. This phenomenon is known as sound conditioning or 'toughening'. Reactive oxygen intermediates have been implicated in noise-induced cochlear damage. To evaluate if in situ antioxidant processes may play a role in the toughening phenomenon initiated by low level noise exposure we analyzed glutathione reductase, gamma-glutamyl cysteine synthetase, and catalase in stria vascularis and organ of Corti fractions from cochleae of chinchillas exposed to a sound conditioning paradigm. Chinchillas were either (A) kept in quiet cages (control), (B) exposed to conditioning noise of a 0.5 kHz octave band (90 dB for 6 h/day for 10 days), (C) exposed to high level noise (105 dB for 4 h) or (D) exposed to conditioning noise (B) followed by exposure to the higher level noise (C). Each of the noise exposure conditions (B, C, D) induced changes in the levels of these three antioxidant enzymes. The enzyme-specific activity data for the four subject groups support the following two hypotheses. (1) Changes in glutathione reductase, gamma-glutamyl cysteine synthetase, and catalase play a role in attenuating hearing loss associated with sound conditioning followed by high level noise. (2) Hair cells in the organ of Corti are protected from noise-induced damage by increasing stria vascularis levels of catalase, a hydrogen peroxide scavenging enzyme, and of enzymes involved in maintaining glutathione in the reduced state. The model formulated by these hypotheses suggests that agents that protect or augment the glutathione system in the cochlea may be protective against noise-induced hearing loss.

Multiple organ failure - death of consumer protection?

The enormously profitable complementary medicines, dietary supplements and traditional medicines markets are largely unregulated internationally and South Africa. Attempts to ensure that consumers are not exposed to harmful or ineffective products have met with varying success around the world.