Regulation of calcitonin release from the 6.23 rat C-cell line by cyclic nucleotide analogues and pharmacological mediators

Calcitonin release from 6.23 rat medullary thyroid carcinoma C-cells was stimulated by dibutyryl cyclic AMP and inhibited by dibutyryl cyclic GMP in concentration dependent fashion. Histamine, isoproterenol, prostaglandin E₂ and Bay K 8644 stimulated calcitonin release, while acetylcholine and serotonin had no significant effect on CT release.     

The importance of non-linearities in large forecasting models with stochastic error processes

This paper considers the consequences of the stochastic error process in large non-linear forecasting models. As such models are non-linear, the deterministic forecast is neither the mean nor the mode of the density function of the endogenous variables. Under a specific assumption as to the class of the non-linearity it is shown that the deterministic forecast is actually the vector of marginal medians of the density function. Stochastic simulation techniques are then used to test whether one large forecasting model actually lies within this class.     

Morphological integration in the cranium during anuran metamorphosis

We examined the role of thyroid hormone in mediating morphological integration between cranial cartilage and bone during anuran metamorphosis. Exogenous T3 applied to premetamorphic tadpoles (Bombina orientalis) via intracranial implants of plastic micropellets precociously induced typical metamorphic changes in both tissues, but also dissociated the relative timing of developmental events between them. Morphological integration between the two primary cranial tissues is achieved in part by each tissue responding independently to endocrine factors and does not reflect a tight developmental coupling between them.     

Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels

Mutations in the period (per) gene of Drosophila melanogaster affect both circadian and ultradian rhythms. Levels of per gene product undergo circadian oscillation, and it is now shown that there is an underlying oscillation in the level of per RNA. The observations indicate that the cycling of per-encoded protein could result from per RNA cycling, and that there is a feedback loop through which the activity of per-encoded protein causes cycling of its own RNA.     

Different antiviral spectra of human macrophage interferon activities

The antiviral activity of alpha-interferon (IFN-alpha) produced by human leukocytes in response to viral infection has been considered to be independent of the virus which induced its production. Recently, however, IFN-alpha has been found to include at least eight different subtypes, as indicated by measurement of antigenic variability, DNA hybridization and amino acid sequencing. We considered the possibility that interferon heterogeneity may play a part in enhancing host antiviral defence and now present data suggesting that purified human macrophages, when exposed to different viruses, produce interferons having differing spectra of antiviral activity. These findings may provide a functional correlation for IFN-alpha heterogeneity.     

Chromosome 5 allele loss in human colorectal carcinomas

That the sporadic and inherited forms of a particular cancer could both result from mutations in the same gene was first proposed by Knudson. He further proposed that these mutations act recessively at the cellular level, and that both copies of the gene must be lost for the cancer to develop. In sporadic cases both events occur somatically whereas in dominant familial cases susceptibility is inherited through a germline mutation and the cancer develops after a somatic change in the homologous allele. This model has since been substantiated in the case of retinoblastoma, Wilms tumour, acoustic neuroma and several other tumours, in which loss of heterozygosity was shown in tumour material compared to normal tissue from the same patient. The dominantly inherited disorder, familial adenomatous polyposis (FAP, also called familial polyposis coli), which gives rise to multiple adenomatous polyps in the colon that have a relatively high probability of progressing to a malignant adenocarcinoma, provides a basis for studying recessive genes in the far more common colorectal carcinomas using this approach. Following a clue as to the location of the FAP gene given by a case report of an individual with an interstitial deletion of chromosome 5q, who had FAP and multiple developmental abnormalities, we have examined sporadic colorectal adenocarcinomas for loss of alleles on chromosome 5. Using a highly polymorphic 'minisatellite' probe which maps to chromosome 5q we have shown that at least 20% of this highly heterogeneous set of tumours lose one of the alleles present in matched normal tissue. This parallels the assignment of the FAP gene to chromosome 5 (see accompanying paper) and suggests that becoming recessive for this gene may be a critical step in the progression of a relatively high proportion of colorectal cancers.