The use of tracheal implants in toxicology and carcinogenesis research

Tracheal implants have served as an important experimental pathology tool with which to study the toxic and/or carcinogenic effects of chemicals upon upper respiratory tract epithelium. Initial studies with this method utilized heterotopic rat tracheal transplants which were exposed to compounds of interest, and assessed for toxic and/or carcinogenic endpoints. Grafts containing rodent tissue have proved useful for studying the cellular and biochemical features of neoplastic progression at different time intervals following in vivo exposure to carcinogens. More recent studies have utilized epithelial denuded tracheal implants inoculated with respiratory cell populations, and xenografted into immunodeficient nu/nu mice. This technique permits the study of airway epithelium from a variety of species, including man. The advent of molecular pathology techniques such as in situ hybridization will further expand the uses of tracheal implant technology for studies with xenografted human tissues. Such implants should prove useful for the examination of species- and tissue-specific characteristics of growth and differentiation by providing a bridge between cell culture and whole animal studies.     

Differentiation between organic and functional psychiatric illness in the elderly: An evaluation of four cognitive tests

One hundred and sixty-four patients admitted to a psychogeriatric unit were given a combination of four different cognitive tests: the Mini Mental State Examination (MMSE), the Abbreviated Mental Test Score, The Felix Post Unit Score and the compilation of tests recommended by the MRC Alzheimer's Disease Workshop. The tests were compared with respect to their ability to sort accurately cases of dementia and depression, and the effects of age and education on test score and misclassification rate with diagnosis controlled for. The MMSE had a very high misclassification rate for the poorly educated and depressed group. The logistical discriminant functional analysis selected only eight items as the best discriminators between organic/ functional or dementia/depression groups. Only one of these eight was not either a memory or orientation test. The value of simply adding up tests of different aspects of cognitive function in dementia assessment or screening is questioned.     

Becoming a mother — an analysis of women's experience of early motherhood

This paper presents the results of a qualitative study conducted by midwife researchers into women's experience of new motherhood. Data were collected using focus groups involving 55 first-time mothers and analysed using grounded theory method. The analysis produced six categories: 'realizing', 'unready', 'drained', 'aloneness', 'loss' and 'working it out'. The core category, 'becoming a mother', integrates all other categories and encapsulates the process of change experienced by women. Also explained are factors mediating the often distressing experience of becoming a mother. The analysis provides a conceptualization of early motherhood enabling the development of strategies for midwives, nurses and others helping women negotiate this challenge.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Rodent model of reproductive tract leiomyomata. Establishment and characterization of tumor-derived cell lines.

Uterine myometrial tumors are the most commonly found gynecological neoplasm in women. The underlying causes of uterine leiomyomata are poorly understood, a result in part of the absence of a good animal model system in which to study these tumors. This report describes a novel rat model (Eker rat) in which spontaneous gynecological smooth muscle tumors arise with a high frequency. Leiomyomas are the predominant reproductive tract tumor that arise in these animals, although leiomyosarcomas have also been observed. Cell lines have been established from both the benign and malignant lesions. All of the lines express smooth muscle-specific actin, and leiomyoma-derived cell lines express desmin. Two of the cell lines are tumorigenic in nude mice, and the lines are variable for expression of estrogen and progesterone receptors. These lines are the first rodent tumor-derived lines to be established from leiomyomata and are the only lines available from a hereditary form of these tumors. Together with Eker rats that spontaneously develop leiomyomata, they constitute an in vitro/in vivo model system for gaining insights into the mechanism of transformation of uterine smooth muscle cells and the role of steroid hormones and hormone receptors in myometrial tumorigenesis.     

Occurrence of neuropeptide Y (NPY)-like immunoreactivity in catecholamine neurons in the human medulla oblongata

We report here the coexistence of a neuropeptide and catecholamines in neurons of the human brain. Using indirect immunofluorescence histochemistry, combined with elution and restaining experiments, neurons in the medulla oblongata of man were demonstrated to contain both a neuropeptide Y-like peptide and the catecholamine synthesizing enzyme tyrosine hydroxylase.