Infiltrating micropapillary carcinoma of the breast. Cytologic findings

OBJECTIVE: To examine the cytologic features of infiltrating micropapillary carcinoma (IMPC). METHODS: Using the histopathology files of one of the authors (I.J.B.), we retrospectively identified 20 IMPC cases (pure, 12; partial micropapillary carcinoma differentiation, 8) with corresponding cytology. We evaluated the cases for cellularity, atypia, architecture and background. RESULTS: All cases were diagnostic of malignancy, characterized by atypical cells present predominantly in three-dimensional clusters and single cells, facilitating the diagnosis. The clusters had cell ball and papillarylike arrangements, like the morular growth pattern seen on histopathology. Apocrine cytology was present in 12 cases, focal mucin background in 5 and psamomma bodies in 2. The differential diagnosis includes primary papillary neoplasms of the breast, metastatic ovarian papillary serous carcinoma, apocrine and colloid carcinoma of the breast, and intraductal carcinoma (micropapillary type). CONCLUSION: As in histopathology, the cytologic features of IMPC are unique and should be recognized due to its aggressive behavior.     

The variability of the hepatitis B virus genome: statistical analysis and biological implications

A statistical analysis of the nucleotide sequence variability in 14 published hepatitis B virus (HBV) genomes was carried out using parametric and nonparametric methods. A parametric statistical model revealed that the different regions of the genome differed significantly in their variability. The conclusion was supported by a nonparametric kernel-density model of the HBV genome. Genes S, C, and P, region X, the precore region, and the pre-S2/pre-S1 regions were ranked in order of increasing variability. In many instances, conserved regions of the genome identified with sequences of known function in HBV biology. However, other characterized regions (such as pre-S) showed much variability despite the involvement of their encoded peptides in specific functions. Point mutations that may result in the formation of stop codons and amino acid changes may affect the clinical picture of HBV infection and may be reflected in atypical serological patterns.      

Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients.

Based on breast cancer families with multiple and/or early-onset cases, estimates of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may be as high as 85%. The risk for individuals not selected for family history or other risk factors is uncertain. We determined the frequency of the common BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268 anonymous Ashkenazi Jewish women with breast cancer, regardless of family history or age at onset. DNA was analyzed for the three mutations by allele-specific oligonucleotide hybridization. Eight patients (3.0%, 95% confidence interval [CI] 1.5%-5.8%) were heterozygous for the 185delAG mutation, two (0.75%, 95% CI 0.20-2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT mutation. The lifetime risk for breast cancer in Ashkenazi Jewish carriers of the BRCA1 185delAG or BRCA2 6174delT mutations was calculated to be 36%, approximately three times the overall risk for the general population (relative risk 2.9, 95% CI 1.5-5.8). For the 5382insC mutation, because of the low number of carriers found, further studies are necessary. The results differ markedly from previous estimates based on high-risk breast cancer families and are consistent with lower estimates derived from a recent population-based study in the Baltimore area. Thus, presymptomatic screening and counseling for these common mutations in Ashkenazi Jewish women not selected for family history of breast cancer should be reconsidered until the risk associated with these mutations is firmly established, especially since early diagnostic and preventive-treatment modalities are limited.     

Mimicry on the QT(L): genetics of speciation in Mimulus

Ecological studies suggest that hummingbird-pollinated plants in North America mimic each other to increase visitation by birds. Published quantitative trait locus (QTL) data for two Mimulus species indicate that floral traits associated with hummingbird versus bee pollination results from a few loci with major effects on morphology, as predicted by classical models for the evolution of mimicry. Thus, the architecture of genetic divergence associated with speciation may depend on the ecological context.     

Novel chromatic and structural biomarkers of diet in carotenoid-bearing plumage

Previous attempts to establish a link between carotenoid-based plumage reflectance and diet have focused on spectral features within the human visible range (400-700 nm), particularly on the longer wavelengths (550-700 nm) that make these plumages appear yellow, orange or red. However, carotenoid reflectance spectra are intrinsically bimodal, with a less prominent but highly variable secondary reflectance peak at near-ultraviolet (UV; 320-400 nm) wavelengths visible to most birds but not to normal humans. Analysis of physical reflectance spectra of carotenoid-bearing plumages among trophically diverse tanagers (Thraupini, Emberizinae, Passeriformes) indicated that both the absolute and relative (to long visible wavelengths) amounts of short waveband (including UV) reflectance were lower in more frugivorous species. Striking modifications to the branched structure of feathers increased with frugivory. These associations were independent of phylogenetic relatedness, or other physical (specimen age, number of carotenoid-bearing patches) or ecological (body size, elevation) variables. By comparison, reflectance at longer visible wavelengths ('redness') was not consistently associated with diet. The reflectance patterns that distinguished frugivores should be more apparent to UV-sensitive birds than to UV-blind humans, but humans can perceive the higher plumage gloss produced by modified gross feather structure. Basic aspects of carotenoid chemistry suggest that increases in pigment concentration and feather dimensions reduce short waveband reflectance by the plumages of frugivores.     

Asymmetrical expression of transsexual phenotypes in hummingbirds

I present evidence for asymmetry in the expression of transsexual traits in adult hummingbirds. Among females, individuals with male-like plumage are common and define a continuous range of variation. Among males, individuals with female-like plumage are rare and define discontinuous plumage morphs. Quantitative characters also distinguish transsexuals from other members of their sex, but the characters involved differ for male-like females (bill length) and female-like males (bill, wing and tail length). Gonadal development is correlated with transsexuality only in males; female-like males have significantly smaller testes than male-like males. Both sexes demonstrate a significant negative association between plumage brightness and bill length. This association suggests an ecological basis for transsexuality because differences in plumage and bill morphology are associated with differences in foraging behaviour within and between hummingbird species. Morphological differences between transsexuals and non-transsexuals imply that plumage sexual dimorphism is more likely to evolve through changes in the frequency of female, rather than male, transsexual variants.     

On the ecological basis of interspecific homoplasy in carotenoid-bearing signals

Evidence that similar color patterns occur in unrelated animals with different habits undermines the traditional view that homoplasy evolves through shared ecological selection pressures. Carotenoid pigments responsible for many yellow to red signals exhibit two related properties that could link ecology with appearance by nontraditional means. Ecologic homoplasy could arise through ecophenotypy because all animals must obtain carotenoids through their diet. Such homoplasy also could be hidden from view because increased carotenoid levels are more strongly encoded by decreased reflectance over ultraviolet (UV) wavelengths invisible to humans. To explore these possibilities, I examined apparent matches or mismatches between color and ecology among insectivorous (low carotenoid diet) and frugivorous (high carotenoid diet) bird species in relation to the typical yellow and black plumage pattern of insectivorous, UV-sensitive titmice (Paridae). Diagnostic features of reflectance spectra indicated that all yellow plumages resulted from carotenoids, black plumages from melanins, and olive green plumages from codeposition of both pigments. However, reflectance by carotenoid-bearing plumages correlated with diet independent of plumage pattern; compared to the insectivores, frugivores had reduced amounts of UV reflectance, and to a lesser extent, "red shifts" in longer-wavelength reflectance. Furthermore, an asymptotic decrease in amount of UV with increased redness implied that plumage reflectance of insectivorous species differed more over UV wavelengths, whereas that of frugivorous species differed more over longer wavelengths. I verified that dietary links to plumage reflectance resulted from greater amounts of plumage carotenoids in frugivores, presumably due to their carotenoid-rich diets. All of these ecological associations transcended post-mortem or post-breeding color change, and phylogeny. Thus, predictable associations between avian-visible plumage reflectance, pigmentation, and diet across evolutionary scales may arise directly (diet per se) or indirectly (honest signaling of diet) by ecophenotypy, although various genetic factors also may play a role.     

Submerged growth of the cultivated mushroom,Agaricus bisporus

Agaricus bisporus grew well in submerged culture in a medium containing malt extract, phosphate, and casein. Moderate growth occurred in defined media containing glucose, asparagine, phenylalanine, vitamins and minerals. Other amino acids did not stimulate growth. Growth was stimulated by vegetable oils, partly due to utilization of the oils, and partly to a more complex mechanism. Oleates had the same effect as vegetable oils; palmitates a lesser one. In shaken flasks maximum yield was reached after 22–24 days and in stirred and aerated fermentors after 8–10 days. Besides dry weight of mycelium, laccase activity was determined. The latter determination is suitable for a rapid estimation of the growth in routine experiments. The flavour of the mycelium was like that of mushrooms but weaker. It was strongest in standing liquid cultures and on solid media. The mycelium grown in submerged culture was suitable as spawn for mushroom culture. Presented at the First International Mycological Congress, Exeter, 7–16 September 1971, and at the Meeting of the Netherlands Society for Microbiology, Rotterdam, 8 December 1971. We thank the Mushroom Experiment Station, Horst, the Netherlands, for kindly supplying the compost for fructification experiments and Mr. P. Arntz, M.Sc., for advice in the fermentor work. F. IJ. Dijkstra is indebted to the Royal Netherlands Fermentation Industries (Gist-Brocades), Delft, for a research grant.