Genetically determined chromosome instability syndromes

Spontaneously increased chromosomal instability is well documented in the three autosomal recessive diseases, Fanconi's anemia (FA), Bloom's syndrome (BS), and ataxia telangiectasia (AT). Other conditions have been reported to be associated with chromosomal breakage. Some are still single observations: in Werner's syndrome only fibroblasts are affected, and systemic sclerosis may not be an inherited disease. Various aspects of FA, BS, and AT are discussed which have emerged since recent reviews have been published. The differential diagnosis in FA has become more important than it was in the past. Proven heterogeneity in FA demands definition of what to name FA and FA variants. The analysis of cancer frequencies and types in FA and AT lacks important clues. This should stimulate all of us to mutual exchange of data and creation of registries not only of patients and follow-ups, but also of characterized cell strains. A synopsis of results from cell and cytogenetic studies demonstrates similarities and differences in detail of the general phenomenon of chromosomal instability which FA, BS, and AT share. Results from biochemical studies at the DNA level together with cytogenetic findings indicate different but still undefined failures in DNA metabolism or DNA repair mechanisms due to the different genes. A new approach to analyzing the impairment of DNA repair in FA is briefly described. DNA related enzymes are produced in the cytoplasm and have to be transported to the nucleus. The subcellular distribution of topoisomerase activity was found to be unusual in three placentas of FA patients. Other DNA enzymes were distributed normally. Thus, a specific mechanism for movement of the enzyme through the nuclear membrane seems to be defective.     

Use of substance P fragments to differentiate substance P receptors of different tissues

The C- and N-terminal fragments of substance P were compared to the parent molecule with respect to their ability to: (a) contract the isolated guinea pig ileum, (b) induce salivation in the rat, (c) excite single cat dorsal horn neurones, and (d) induce scratching by intracranial injections in mice. C-terminal fragments as small as the heptapeptide were potent SP agonists on all assay systems. C-terminal fragments containing five amino acids or less were, at most, only weakly active. The C-terminal hexapeptide was a potent SP receptor stimulant on the isolated guinea pig ileum and, when directly applied by microiontophoresis, on cat dorsal horn neurons. However, the same compound was only 2-5% as potent as substance P in eliciting salivation and scratching in vivo, an indication that this fragment may be especially labile to enzymatic degradation. N-terminal fragments were totally inactive on the isolated guinea pig ileum. On the rat salivation and central nervous system assays, however, N-terminal fragments were capable of weak SP-like activity. It is concluded that SP receptors exist in multiple forms which we have labelled SP1 and SP2 receptors for those insensitive or sensitive to N-terminal fragments, respectively.     

The jelly canal marker of polarity for sea urchin oocytes, eggs, and embryos

The jelly coat of a sea urchin egg possesses a narrow conical channel which identifies the animal pole. This rarely seen structure was first reported by Boveri in 1901 and is easily demonstrated by immersing freshly ovulated eggs into an ink suspension. The jelly canal, as this feature is called, fills with ink particles as the jelly swells. The jelly canal occurs on full-sized primary oocytes and unfertilized eggs. When filled with ink it serves as a useful marker of the animal pole during fertilization and early development when it is not otherwise visible. A common synonym for the jelly canal is ‘micropyle’, but this is a misnomer because sperm do not selectively pass through it for fertilization. The presence of the jelly canal on oocytes suggests how it might form and does not prove that the animal-vegetal polar axis in sea urchin eggs is defined before meiotic maturation.     

Oocyte-follicle cell relationships in a starfish

Summary The follicle cells which surround the oocytes of starfish are known to both release the hormone 1-methyladenine and to respond to it by an active movement which forms a component of the spawning response to the hormone. In Patiria miniata these flagellated cells are located peripheral to the oocyte and have long cytoplasmic processes which penetrate the vitelline layer to the egg surface to form an adhering zonule-like junction. Within the follicle cell cytoplasm are located elongate filamentous bands which appear to represent a component of the contractile mechanism that mediates follicle cell response to 1-methyladenine. These bands do not resemble the filaments of vertebrate smooth muscle cells (quantity, distribution and size of filaments; lack of dense bodies in the filament mass), nor the contractile units of the superficial epithelium of lower vertebrate follicles.This investigation was supported by grants HD-07194 and HD-12499 from the National Institutes of Health. We are indebted to Mr. James D. Huber for able technical assistance     

Epithelial differentiation and taste buds in the soft palate of the monkey,Macaca irus

A combination of light, transmission and scanning electron microscopy was employed to demonstrate the occurrence, arrangement and structure of taste buds in the oral mucosa of the soft palate of monkeys (Macaca irus). Taste buds are found in aggregates confined to 0.15 to 0.3 mm wide, round islands of keratinizing epithelium embedded in the normally non-keratinizing integument. Topography, configuration and structure of these epithelial islands and their taste buds are described, and the question of a developmental and functional interrelationship between epithelial differentiation and properties, and taste bud function is discussed.     

Dentist phobia

This study analyzes so-called hopeless gaggers, i.e., patients in whom dental treatment and wearing of a prosthesis produced a retching or vomiting reaction, in order to investigate the sources and properties of this pathologic reaction. In 35 patients, an anamnestic inquiry, a determination of the reflexogenic zone, a recording of the peripheral pattern of the pathologic reflex, and extinction training were performed. A group of six normal persons served as a comparison group. It was shown that patients, in comparison with normals, had an enlarged receptive field, were sensitive to a broader population of stimuli, and showed precursors and aftereffects of the retching-vomiting not found in normals. This pathologic reaction was the symptom of different psychopathologic processes, such as specific fear, repugnance-fear-based disturbances, diffuse anxiety, goal-directed behavior, depressive states and, at least in one case, visceral pathology. The various patients differed with respect to properties of the reaction as well as in the sensitivity to the extinction procedure. It is discussed that different integrative nervous processes play a role in the origin and development of the syndrome: activation of unconditional reflexes, activation of classic and instrumental conditional reflexes, activation of such reflexes by an increase of the reactivity level of specific and unspecific structures of the brain, generalization of stimuli, etc.     

A correlation between BCL-2 modifying factor,p53 and livin gene expressions in cancer colon patients

Accumulating evidence has revealed that livin gene and BCL-2 modifying factor (BMF) gene are closely associated with the initiation and progression of colon carcinoma by activating or suppressing multiple malignant processes. Those genes that can detect colon - cancer are a promising approach for cancer screening and diagnosis. This study aimed to evaluate correlation between livin, BMF and p53 genes expression in colon cancer tissues of patients included in the study, and their relationship with clinicopathological features and survival outcome in those patients. In this study, 50 pathologically diagnosed early cancer colon patients included and their tissue biopsy with 50 matched adjacent normal tissue, and 50 adenoma tissue specimens were analyzed for livin gene and BMF gene expressions using real time PCR. The relationship of those genes expressions with clinicopathological features, tumor markers, Time to Progression and overall survival for those patients were correlated in cancer colon group. In this study, there was a significant a reciprocal relationship between over expression of livin gene and down regulation of BMF and p53 genes in colon cancer cells. Livin mRNA was significantly higher, while BMF and p53 mRNA were significantly lower in colorectal cancer tissue compared to benign and normal colon tissue specimens (P < 0.001), however, this finding was absent between colon adenomas and normal mucosa. There was a significant association between up regulation of livin and down regulation of BMF and p53 expressions with more aggressive tumor (advanced TNM stage), rapid progression with metastasis and decreased overall survival in cancer colon patients, hence these genes can serve as significant prognostic markers of poor outcome in colon cancer patients. This work highlights the role of livin, BMF and p53 genes in colorectal tumorigenesis and the applicability of using those genes as a diagnostic and prognostic markers in patients with colon carcinoma and as a good target for cancer colon treatment in the future.