Attitudes of subjects at risk and their relatives towards genetic counselling in Huntington''s chorea.

Ninety-two patients suffering from Huntington's chorea (HC) and their spouses, and 91 subjects with an affected parent and their spouses, living in three counties of industrial South Wales, have been studied regarding their knowledge of their inheritance of the disorder. Particular attention was paid to its influence on their attitudes towards child-bearing, telling their children of the risks, and predictive tests. Only 12% of the patients were known to have received professional advice before completing their families, in contrast to 68% of the sample at risk. It is estimated that 82% of the patients and 60% of the subjects at risk had, or might have, restricted their family size had they known in time. The majority found genetic counselling helpful, but did not necessarily wish to alter their child-bearing plans in consequence. It was clear that information provided by the family alone was usually inadequate and that this applied to the present generation at risk as well as to previous generations. It was concluded that the burden of telling children the risks is too great for most parents and that professional help is needed. The long term impact of genetic counselling on the incidence of the disease is impossible to assess without continued monitoring, but preliminary results are encouraging. Attitudes towards a predictive test reflected much conflict: although 56% overall wished to take one, only 40% of those who were parents wished to know if they were at risk of passing the gene on to their children. Few subjects reported severe social stress on learning of their genetic risks, but about one in four reported experiencing significant anxiety.     

Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

Mechanisms of enhanced prevalence of asthma and atopy in developed countries

Atopy — a T helper 2 cell driven hypersensitivity to innocuous antigens (allergens) which causes most cases of asthma — is of complex genetic and environmental origins. There is compelling epidemiological evidence for a rise in atopic disease in ‘westernised’ communities. The changing pattern of microbial exposure in early childhood is suggested to be the principal candidate mechanism for this rise.     

Cardiac and respiratory patterns in normal infants and victims of the sudden infant death syndrome

Victims of the sudden infant death syndrome (SIDS) have higher overall heart rates prior to death than do control infants (1). The objective of this study was to partition these heart rate differences by state and to identify any state-dependent differences in heart rate variability and respiratory rate and variability. Twenty-two recordings of electrocardiogram (ECG) and respiration from 16 infants who subsequently died of SIDS were compared with 66 recordings of age-matched control infants. Median cardiac and respiratory rate and variability were computed for each sleep state in each recording, and one-way analysis of variance tests were performed for each variable for infants less than 1 month and for infants greater than 1 month of age. Heart rate was higher in SIDS victims less than 1 month of age than in age-matched controls during all sleep-waking states. SIDS victims greater than 1 month showed higher heart rates during rapid eye movement sleep only. Heart rate variability was also diminished during waking in victims less than 1 month, but much of this difference could be attributed to increased heart rate. These results suggest that, as a group, SIDS victims differ physiologically from control infants and that these differences may be especially prominent during particular sleep-waking states.     

Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.

Loss of the cell adhesion molecule E-cadherin has been observed in a variety of human carcinomas, and germline E-cadherin mutations have been found in several familial cases of diffuse gastric cancer. We sought to determine the prevalence and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We performed comprehensive sequencing of the coding region, loss of heterozygosity (LOH) analysis, and immunohistochemical protein expression determination on 40 sporadic gastric adenocarcinomas. In total, 7 of 25 diffuse-type cancers harbored genetic alterations in the E-cadherin gene. Novel mutations predicted to significantly compromise protein function were found within 4 of these cancers, 2 of which harbored alterations resulting in biallelic inactivation of the gene product. Three diffuse cancers failed to amplify Exon 8 of E-cadherin, suggesting the presence of a homozygous abnormality. Notably, one germline E-cadherin mutation was also identified within these "sporadic" diffuse cancers. Significant gene mutations were not found in the 14 intestinal-type or histologically mixed cancer. Immunohistochemistry revealed aberrant or negative protein expression in seven diffuse-type tumors, four of which correlated with the genetic alterations. Both diffuse and intestinal-type tumors exhibited low rates of LOH, suggesting that allelic loss at the locus is not a common mechanism for E-cadherin inactivation during gastric tumorigenesis. Our observations suggest that inactivation of the E-cadherin gene occurs only in a subset of diffuse-type gastric cancers, as the majority of cases did not contain genetic alterations or identifiable protein abnormalities. Germline E-cadherin alterations, although rare, may underlie some diffuse gastric cancer cases that have important biologic and practical implications     

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.