Cancer culture: Epidemics, human behaviour and the dubious search for new risk factors

The rise of melanoma and the almost complete decline of stomach cancer clearly reflect disturbances of human culture during the 20th century. Environmental factors play a dominant role in the epidemiology of melanoma and many other malignancies.

The toxins of Lyngbya majuscula and their human and ecological health effects

Lyngbya majuscula is a benthic filamentous marine cyanobacterium, which in recent years appears to have been increasing in frequency and size of blooms in Moreton Bay, Queensland. It has a worldwide distribution throughout the tropics and subtropics in water to 30m. It has been found to contain a variety of chemicals that exert a range of biological effects, including skin, eye and respiratory irritation. The toxins lyngbyatoxin A and debromoaplysiatoxin appear to give the most widely witnessed biological effects in relation to humans, and experiments involving these two toxins show the formation of acute dermal lesions. Studies into the epidemiology of the dermatitic, respiratory and eye effects of the toxins of this organism are reviewed and show that Lyngbya induced dermatitis has occurred in a number of locations. The effects of aerosolised Lyngbya in relation to health outcomes were also reported. Differential effects of bathing behaviour after Lyngbya exposure were examined in relation to the severity of health outcomes. The potential for Lyngbya to exhibit differential toxicologies due to the presence of varying proportions of a range of toxins is also examined. This paper reviews the present state of knowledge on the effects of Lyngbya majuscula on human health, ecosystems and human populations during a toxic cyanobacterial bloom. The potential exists for toxins from Lyngbya majuscula affecting ecological health and in particular marine reptiles. (C) 2001 Elsevier Science Ltd. All rights reserved.

Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors

Using differential display-polymerase chain reaction, we identified a novel gene sequence, designated solid tumor-associated gene 1 (STAG1), that is upregulated in renal cell carcinoma (RCC). The full-length cDNA (4839 bp) encompassed the recently reported androgen-regulated prostatic cDNA PMEPA1 and so we refer to this gene as STAG1/PMEPA1, Two STAG1/PMEPA1 mRNA transcripts of approximately 2.7 an 5 kb, with identical coding regions but variant 3' untranslated regions, were predominantly expressed in normal prostate tissue and at lower levels in the ovary. The expression of this gene was upregulated in 87% of RCC samples and also was upregulated in stomach and rectal adenocarcinomas. In contrast, STAG1/PMEPA1 expression was barely detectable in leukemia and lymphoma samples, Analysis of expressed sequence tag databases showed that STAG1/PMEPA1 also was expressed in pancreatic, endometrial, and prostatic adenocarcinomas. The STAG1/PMEPA1 cDNA encodes a 287-amino-acid protein containing a putative transmembrane domain and motifs that suggest that it may bind src homology 3- and tryptophan tryptophan domain-containing proteins. This protein shows 67% identity to the protein encoded by the chromosome 18 open reading frame 1 gene. Translation of STAG1/PMEPA1 mRNA in vitro showed two products of 36 and 39 kDa, respectively, suggesting that translation may initiate at more than one site. Comparison to genomic clones showed that STAG1/PMEPA1 was located on chromosome 20q13 between microsatellite markers D20S183 and D20S173 and spanned four exons and three introns. The upregulation of this gene in several solid tumors indicated that it may play an important role in tumorigenesis. (C) 2001 Wiley-Liss, Inc.

MUC13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells

Transmembrane mucins are glycoproteins involved in barrier function in epithelial tissues. To identify novel transmembrane mucin genes, we performed a tblastn search of the GenBank(TM) EST data bases with a serine/ threonine-rich search string, and a rodent gene expressed in bone marrow was identified. We determined the cDNA sequence of the human orthologue of this gene, MUC13, which localizes to chromosome band 3q13.3 and generates 3.2-kilobase pair transcripts encoding a 512-amino acid protein comprised of an N-terminal mucin repeat domain, three epidermal growth factor-like sequences, a SEA module, a transmembrane domain, and a cytoplasmic tail (GenBank(TM) accession no. AF286113), MUC13 mRNA is expressed most highly in the large intestine and trachea, and at moderate levels in the kidney, small intestine, appendix, and stomach, In situ hybridization in murine tissues revealed expression in intestinal epithelial and lymphoid cells. Immunohistochemistry demonstrated the human MUC13 protein on the apical membrane of both columnar and goblet cells in the gastrointestinal tract, as well as within goblet cell thecae, indicative of secretion in addition to presence on the cell surface. MUC13 is cleaved, and the beta -subunit containing the cytoplasmic tail undergoes homodimerization, Including MUC13, there are at least five cell surface mucins expressed in the gastrointestinal tract.

Relationship between endosomes and lysosomes

Delivery of endocytosed macromolecules to lysosomes occurs by means of direct fusion of late endosomes with lysosomes. This has been formally demonstrated in a cell-free content mixing assay using late endosomes and lysosomes from rat liver. There is evidence from electron microscopy Studies that the same process occurs in intact cells. The fusion process results in the formation of hybrid organelles from which lysosomes are reformed. The discovery of the hybrid organelle has opened up three areas of investigation: (i) the mechanism of direct fusion of late endosomes and lysosomes, (ii) the mechanism of re-formation of lysosomes from the hybrid organelle, and (iii) the function of the hybrid organelle. Fusion has analogies with homotypic vacuole fusion in yeast. It requires syntaxin 7 as part of the functional trans-SNARE [SNAP receptor, where SNAP is soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein] complex and the release of lumenal calcium to achieve membrane fusion. Reformation of lysosomes from the hybrid organelle occurs by a maturation process involving condensation of lumenal content and probably removal of some membrane proteins by vesicular traffic. Lysosomes may thus be regarded as a type of secretory granule, storing acid hydrolases in between fusion events with late endosomes. The hybrid organelle is predicted to function as a 'cell stomach', acting as a major site of hydrolysis of endocytosed macromolecules.

Cloning and functional analysis of the Sry-related HMG box gene, Sox18

The Sox gene family (Sry like HMG box gene) is characterised by a conserved DNA sequence encoding a domain of approximately 80 amino acids which is responsible for sequence specific DNA binding. We initially published the identification and partial cDNA sequence of murine Sox18, a new member of this gene family, isolated from a cardiac cDNA library. This sequence allowed us to classify Sox18 into the F sub-group of Sox proteins, along with Sox7 and Sox17. Recently, we demonstrated that mutations in the Sox18 activation domain underlie cardiovascular and hair follicle defects in the mouse mutation, ragged (Ra) (Pennisi et al., 2000. Mutations in Sox18 underlie cardiovascular and hair follicle defecs in ragged mice. Nat. Genet. 24, 434-437). Ra homozygotes lack vibrissae and coat hairs, have generalised oedema and an accumulation of chyle in the peritoneum. Here we have investigated the genomic sequences encoding Sox18. Screening of a mouse genomic phage library identified four overlapping clones, we sequenced a 3.25 kb XbaI fragment that defined the entire coding region and approximately 1.5 kb of 5' flanking sequences. This identified (i) an additional 91 amino acids upstream of the previously designated methionine start codon in the original cDNA, and (ii);ln intron encoded within the HMG box/DNA binding domain in exactly the same position as that found in the Sox5, -13 and -17 genes. The Sox18 gene encodes a protein of 468 aa. We present evidence that suggests HAF-2, the human HMG-box activating factor-2 protein, is the orthologue of murine Sox18. HAF-2 has been implicated in the regulation of the Human IgH enhancer in a B cell context. Random mutagenesis coupled with GAL4 hybrid analysis in the activation domain between amino acids 252 and 346, of Sox18, implicated the phosphorylation motif, SARS, and the region between amino acid residues 313 and 346 as critical components of Sox18 mediated transactivation. Finally, we examined the expression of Sox18 in multiple adult mouse tissues using RT-PCR. Low-moderate expression was observed in spleen, stomach, kidney, intestine, skeletal muscle and heart. Very abundant expression was detected in lung tissue. (C) 2001 Elsevier Science B.V. All rights reserved.

Characterization of the mouse hnRNP A2/B1/B0 gene and identification of processed pseudogenes

The mouse hnRNP A2/B1/B0 gene has been cloned using a PCR-based strategy and sequenced. Analysis of this sequence showed that the gene organization closely follows that of the human orthologue with 12 exons and 11 introns. The hnRNP A2/B1/B0 gene gives rise to four splice variants through alternative splicing of exons 2 and 9. RT-PCR assays indicated that all splice variants were expressed in mouse brain, skin, and stomach tissues of varying ages, although their ratios to one another varied with age and tissue type. We also identified a small subset of all polyadenylated splice variants that included intron 11, which shows 94% sequence identity between human and mouse. Several processed pseudogenes were identified in the mouse genome. A search of the mouse genome databases located five pseudogenes, four of. which are presumed to be non-functional because of the presence of premature stop codons, large deletions or rearrangements within the coding region. The fifth, which possesses putative promoter elements and has a coding sequence identical to that of the hnRNP A2 mRNA, variant, may be functional. (C) 2002 Elsevier Science B.V. All rights reserved.

Reproductive biology of the eastern shovelnose ray, Aptychotrema rostrata (Shaw & Nodder, 1794), from Moreton Bay, Queensland, Australia

The eastern shovelnose ray, Aptychotrema rostrata (Rhinobatidae), is an endemic batoid common to the east coast of Australia. The reproductive cycle was studied in Moreton Bay, south-eastern Queensland, over a 14-month period. Aptychotrema rostrata is an aplacental yolksac viviparous species with an annual, seasonal reproductive cycle in Moreton Bay. Females mature at 54-66 cm total length, and males at 60-68 cm total length. Gravid females were observed during September-November and parturition occurred in November-December. Vitellogenesis does not proceed in parallel with gestation. Ovulation and copulation probably occur during July-September, resulting in a gestational period of 3-5 months. Uterine fecundity ranges from 4 to 18, with a significant positive relationship between uterine fecundity and maternal body length. In mature males, a peak in the proportion of mature spermatocysts in the testes was observed in July, whereas gonadosomatic index peaked in April.

A case of myoepithelial carcinoma displaying biallelic inactivation of the tumour suppressor gene APC in a patient with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene. It is characterised by the appearance of hundreds to thousands of colorectal adenomas in adolescence and the subsequent development of colorectal cancer. Various extracolonic malignancies are associated with FAP, including desmoids and neoplasms of the stomach, duodenum, pancreas, liver, and brain. We present a family affected by FAP with an exon 14 APC mutation displaying two rare extracolonic lesions, a hepatoblastoma and a myoepithelial carcinoma. The hepatoblastoma was found in a male patient aged 2 years. The second lesion, a myoepithelial carcinoma of the right cheek, was found in a female patient aged 14 years. Inactivation of the normal APC allele was demonstrated in this lesion by loss of heterozygosity analysis, thus implicating APC in the initiation or progression of this neoplasm. This is the first reported case of this lesion in a family affected by FAP.

Trichostome ciliates from Australian marsupials. III. Megavestibulum gen. nov. (Litostomatea : Macropodiniidae)

A new macropodiniid ciliate genus, Megavestibulum, is described which is endocommensal in the stomach of macropodid marsupials. Two new species, M. morganorum and M. kuhri, are described from Macropus dorsalis and Wallabia, bicolor respectively. Megavestibulum is holotrichous, the somatic ciliation arranged into meridional, curving kineties between broad ridges. The interkinetal ridges are lined apically by thick-walled vacuoles similar to those lining the longitudinal grooves of Macropodinium. The conical vestibulum is apical and very large, occupying up to 1/3 of the cell volume. The vestibular lip appears closable and has a cleft which may allow distention of the vestibullum to ingest large food items. The vestibular ultrastructure is similar to that of Macropodinium including the presence of vestibular vacuoles and the hemispherical differentiation of the distribution of small nematodesmata. Many specimens contained ingested whole ciliates of the genera Amylovorax and Polycosta. The structure of the vestibulum suggests that Megavestibulum is adapted for life as an active predator of other stomach ciliates as well as sweeping in small particulates. The morphology of Megavestibulum suggests that it represents the plesiomorphic body plan within the family Macropodiniidae.

Trichostome ciliates from Australian marsupials. IV. Distribution of the ciliate fauna

Trichostome ciliates are associated with many different lineages of herbivorous mammals but there are few comparative studies of these associations in each lineage of herbivores. Here the occurrence of the ciliate fauna in a range of herbivorous marsupials (diprotodonts) is investigated and compared with that of ruminants. A total of 371 potential host animals, representing 33 species and 7 families, were examined for the presence of ciliates. The prevalence of endocommensal ciliates within individual host species varied between 0 and 100%. Of the different dietary groups of marsupials examined, only foregut (macropodids) and hindgut (vombatids) fermentative herbivores were found to harbour ciliates; carnivorous (dasyurids), omnivorous (peramelids) and midgut fermenting herbivores (phalangeroids) all lacked ciliates. The majority of ciliate species were oioxenic, several occurred in closely related hosts and some were able to colonise unnatural hosts in captive populations. Ciliate prevalences were found to vary at all levels: between hosts of different species, between conspecific hosts collected at different localities or seasons and between conspecific hosts at one collecting locality. The faunal composition of the 2 marsupial families which harboured ciliates differed greatly: the vombatid fauna was composed exclusively of amylovoracids whereas the macropodids harboured amylovoracids, polycostids and macropodiniids. In comparison to the ciliate fauna of ruminants, the fauna of macropodids is both depauperate and much more host specific. Low species richness in each host may be due to the large numbers of stomach nematodes in macropodids which compete with and may prey upon the ciliates within the stomach. The high levels of host specificity are probably due to different patterns of ciliate transmission in macropodids as they do not ruminate, eructate or feed indiscriminantly on pasture contaminated with saliva containing ciliates.

Como reagimos e interpretamos os latidos dos cães de acordo com a variação acústica?

Os cães dividem o ambiente com os humanos há milhares de anos e essa relação se torna cada vez mais estreita. Estudos mostram que há comunicação intraespecífica entre os cães e interespecífica entre os cães e os humanos, tanto vocal quanto não-vocal. Os latidos se apresentam hipertrofiados nos cães e acredita-se que isso se deva ao processo de domesticação. Neste estudo, investigamos como os humanos percebem o conteúdo emocional dos latidos e como respondem aos latidos quanto ao grau de irritação percebido, em função das características acústicas de cada chamado. Sessenta participantes, divididos de acordo com a experiência com cães e com o sexo, ouviram 27 sequências de latidos gravadas anteriormente. As sequências de latidos foram montadas artificialmente e categorizadas de acordo com a frequência fundamental, harmonicidade e intervalo entre latidos. Os resultados confirmaram o pressuposto de que tais parâmetros acústicos são importantes para a percepção humana de um conteúdo emocional na vocalização de cães e que causam um impacto emocional em nós, a irritação. Os resultados também foram consistentes com as regras de estrutura-motivação de Morton (1977). Quanto mais baixa a frequência fundamental, maior a agressividade percebida e sons mais agudos e tonais estão relacionados ao medo e ao desespero; quanto mais baixa a harmonicidade, ou seja, quanto mais áspero ou rouco, maior a motivação agressiva. O intervalo entre latidos se mostrou significativo apenas na atribuição da agressividade, quanto mais curtos os intervalos, maior a agressividade percebida. A correlação entre o grau de irritação causado pelos latidos e a percepção das emoções mostrou que quanto maior a percepção de agressividade, medo e desespero, maior o grau de irritação e quanto maior a percepção de brincadeira e felicidade, menor o grau de irritação causado pelos latidos. Esses resultados sugerem que a irritação gerada pelos latidos dos cães está associada a emoções negativas. Quanto ao sexo, os homens obtiveram valores médios significativamente maiores do que as mulheres na avaliação da irritação, o que sugere que os homens possam ter uma menor tolerância com os chamados caninos. Os resultados deste estudo nos levam a concluir que os humanos são capazes de identificar os estados emocionais dos cães através de emissões sonoras. Isto sugere que há uma comunicação interespecífica entre estas espécies e que ambas dividem as mesmas regras acústicas de motivação-estrutural de Morton.

Proportional cancer incidence according to selected sites: comparison between residents in the City of S. Paulo, Brazil: Japanese and Brazilian/Portuguese descent

The percentual distributions of selected sites of cancer cases according to origin, sex and age are compared. Data were obtained from the Registry of Cancer of S. Paulo (School of Public Health of the University of S. Paulo, Brazil). The reference period for inhabitants of Japanese descent was 1969/78 and for those of Brazilian descent, the period was 1969/75. Standardized Proportionate Incidence Ratios (SPIR) with approximate 95% Confidence Intervals (CI) were evaluated using age specific Incidence Ratios of S. Paulo, 1973, as standards. The results agree with findings of previous works on mortality, but show different patterns according to origin. The well known fact that some sub-groups of a population may be different from the overall group is once again brought to the fore. Attention should be drawn to the differences detected for stomach, skin and prostate, in males, and for stomach, skin, cervix and uterus in females.

Geographical patterns of proportionate mortality for the most common causes of death in Brazil

Mortality due to chronic diseases has been increasing in all regions of Brazil with corresponding decreases in mortality from infectious diseases. The geographical variation in proportionate mortality for chronic diseases for 17 Brazilian state capitals for the year 1985 and their association with socio-economic variables and infectious disease was studied. Calculations were made of correlation coefficients of proportionate mortality for adults of 30 years or above due to ischaemic heart disease, stroke and cancer of the lung, the breast and stomach with 3 socio-economic variables, race, and mortality due to infectious disease. Linear regression analysis included as independent variables the % of illiteracy, % of whites, % of houses with piped water, mean income, age group, sex, and % of deaths caused by infectious disease. The dependent variables were the % of deaths due to each one of the chronic diseases studied by age-sex group. Chronic diseases were an important cause of death in all regions of Brazil. Ischaemic heart diseases, stroke and malignant neoplasms accounted for more than 34% of the mortality in each of the 17 capitals studied. Proportionate cause-specific mortality varied markedly among state capitals. Ranges were 6.3-19.5% for ischaemic heart diseases, 8.3-25.4% for stroke, 2.3-10.4% for infections and 12.2-21.5% for malignant neoplasm. Infectious disease mortality had the highest (p < 0.001) correlation with all the four socio-economic variables studied and ischaemic heart disease showed the second highest correlation (p < 0.05). Higher socio-economic level was related to a lower % of infectious diseases and a higher % of ischaemic heart diseases. Mortality due to breast cancer and stroke was not associated with socio-economic variables. Multivariate linear regression models explained 59% of the variance among state capitals for mortality due to ischaemic heart disease, 50% for stroke, 28% for lung cancer, 24% for breast cancer and 40% for stomach cancer. There were major differences in the proportionate mortality due to chronic diseases among the capitals which could not be accounted for by the social and environmental factors and by the mortality due to infectious disease.

Human case of gastric infection by a fourth larval stage of Pseudoterranova decipiens (Nematoda, Anisakidae)

Only three cases of human infection by anisakid nematodes have been reported in Chile since 1976. In the present case, an anisakid worm, identified as a fourth-stage Pseudoterranova decipiens larva, was removed with a gastroendoscopic biopsy clipper from the stomach of a 45 year-old man from southern Chile. The patient, who presented acute epigastric pain and a continuous sensation of having an empty stomach, reported having eaten smoked fish. The worm was fixed in 70% ethanol and cleaned in lactophenol for morphological study. The morphometric characteristics of the worm are described and drawn. Anisakid larvae in fish flesh can be killed by freezing or cooking.