Modelling pH evolution and lactic acid production in the growth medium of a lactic acid bacterium: application to set a biological TTI.

Time temperature integrators or indicators (TTIs) are effective tools making the continuous monitoring of the time temperature history of chilled products possible throughout the cold chain. Their correct setting is of critical importance to ensure food quality. The objective of this study was to develop a model to facilitate accurate settings of the CRYOLOG biological TTI, TRACEO. Experimental designs were used to investigate and model the effects of the temperature, the TTI inoculum size, pH, and water activity on its response time. The modelling process went through several steps addressing growth, acidification and inhibition phenomena in dynamic conditions. The model showed satisfactory results and validations in industrial conditions gave clear evidence that such a model is a valuable tool, not only to predict accurate response times of TRACEO, but also to propose precise settings to manufacture the appropriate TTI to trace a particular food according to a given time temperature scenario.

An iterative sensory procedure to select odor-active associations in complex consortia of microorganisms: application to the construction of a cheese model.

The aim of this study was to develop and validate an iterative procedure based on odor assessment to select odor-active associations of microorganisms from a starting association of 82 strains (G1), which were chosen to be representative of Livarot cheese biodiversity. A 3-step dichotomous procedure was applied to reduce the starting association G1. At each step, 3 methods were used to evaluate the odor proximity between mother (n strains) and daughter (n/2 strains) associations: a direct assessment of odor dissimilarity using an original bidimensional scale system and 2 indirect methods based on comparisons of odor profile or hedonic scores. Odor dissimilarity ratings and odor profile gave reliable and sometimes complementary criteria to select G3 and G4 at the first iteration, G31 and G42 at the second iteration, and G312 and G421 at the final iteration. Principal component analysis of odor profile data permitted the interpretation at least in part, of the 2D multidimensional scaling representation of the similarity data. The second part of the study was dedicated to 1) validating the choice of the dichotomous procedure made at each iteration, and 2) evaluating together the magnitude of odor differences that may exist between G1 and its subsequent simplified associations. The strategy consisted of assessing odor similarity between the 13 cheese models by comparing the contents of their odor-active compounds. By using a purge-and-trap gas chromatography-olfactory/mass spectrometry device, 50 potent odorants were identified in models G312, G421, and in a typical Protected Denomination of Origin Livarot cheese. Their contributions to the odor profile of both selected model cheeses are discussed. These compounds were quantified by purge and trap-gas chromatography-mass spectrometry in the 13 products and the normalized data matrix was transformed to a between-product distance matrix. This instrumental assessment of odor similarities allowed validation of the choice of G312 as the best 10-strain ecosystem.

[HNPCC syndrome (hereditary non polyposis colon cancer): identification and management]. / Le syndrome HNPCC (hereditary non polyposis colon cancer): identification et prise en charge.

BACKGROUND: The hereditary non-polyposis colon cancer (HNPCC) syndrome is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for other organs tumors. HNPCC syndrome is responsible for 5% of colorectal cancers. MAJOR ASPECTS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a two-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. FURTHER DEVELOPMENTS: The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks; other organs being at low lifetime risk, no specific surveillance will be proposed.

Deacidification by Debaryomyces hansenii of smear soft cheeses ripened under controlled conditions: relative humidity and temperature influences.

Model smear soft cheeses were prepared from pasteurized milk inoculated with Debaryomyces hansenii (304, GMPA) and Brevibacterium aurantiacum (ATCC 9175) under aseptic conditions. Debaryomyces hansenii growth and curd deacidification were studied in relation to ripening chamber temperature and relative humidity (RH). A total of 9 descriptors, mainly based on kinetic data, were defined to represent D. hansenii growth (2 descriptors), cheese deacidification (5 descriptors), and cheese ripening (2 descriptors). Regardless of the temperature, when the RH was 85%, D. hansenii growth was inhibited due to limitation of carbon substrate diffusions; consequently, cheese deacidification did not take place. Debaryomyces hansenii growth was most prolific when the temperature was 16 degrees C, and the RH was 95%. Kinetic descriptors of lactate consumption and pH increase were maximal at 16 degrees C and 100% RH. Under these 2 ripening conditions, on d 14 (packaging) the creamy underrind represented a third of the cheese; however, at the end of ripening (d 42), cheese was too liquid to be sold. Statistical analysis showed that the best ripening conditions to achieve an optimum between deacidification and appearance of cheeses (thickness of the creamy underrind) were 12 degrees C and 95 +/- 1% RH.

Thyroid carcinomas after irradiation for a first cancer during childhood.

BACKGROUND: The thyroid gland is among the most radiosensitive organs. However, little is known about the long-term risk of developing a thyroid tumor after fractionated external radiotherapy for cancer during childhood. OBJECTIVE: To study the long-term risk of developing a thyroid tumor in 4096 three-year survivors of childhood cancer treated between May 1942 and December 1985 in 8 centers in France and the United Kingdom, 2827 of whom had received external radiotherapy. METHODS: A wide range of radiation doses were given to the thyroid: 1164 children received less than 0.5 Gy and 812 received more than 5.0 Gy, the average dose being 7.0 Gy. RESULTS: After mean follow-up of 15 years (range, 3-45 years), 14 patients-all of whom had received radiotherapy-developed a clinical thyroid carcinoma. Within the cohort, the relation between radiation dose to the thyroid and risk of thyroid carcinoma and adenoma was similar to that observed in patients who received radiotherapy during childhood for other reasons, such as an excess relative risk per gray of 4 to 8, up to a few gray. In contrast, compared with thyroid cancer incidence in the general population, the standardized incidence of thyroid carcinoma was much higher than expected from the dose-response relationship estimated within the cohort and from patients who received radiotherapy during childhood for other reasons: a dose of 0.5 Gy was associated with a standardized incidence ratio of 35 (90% confidence interval, 10-87) and a dose of 3.6 Gy with a standardized incidence ratio of 73 (90% confidence interval, 28-153). We did not show a reduction in excess relative risk per gray with use of an increasing number of fractions. CONCLUSION: Although we cannot estimate the exact proportion, it is probable that some or all children who are treated for cancer are predisposed to developing a thyroid carcinoma.

Four years analysis of cancer genetic clinics activity in France from 1994 to 1997: a survey on 801 patients. French Cooperative Network/Groupe Génétique et Cancer de la Fédération Nationale des Centres de Lutte Contre le Cancer.

AIM: In order to evaluate the characteristics and the evolution of cancer genetics activity in France, a survey was conducted at the national level during a period of 4 years from 1994 to 1997 through the French Cooperative Network, a multidisciplinary group formed to investigate inherited tumors. METHOD: A questionnaire was sent to all the 29 French non-specialized cancer genetic clinics to evaluate activity during a period of 4 consecutive weeks each year from 1994 to 1997. Items concerning the cancer genetic clinics, the consultees and the types of consultation were explored. RESULTS: A total number of 801 consultees were seen during the period of analysis. Some prominent characteristics of patients attending cancer genetic clinics were found. The majority of these are women (88%), and the mean age of consultees is 48 years. Fifty five percent of consultees are affected with cancer, and breast (personal and/or family history) is the most frequent site involved (63%). A genetic predisposition is certain or likely in about 53% of cases and unlikely in only 13% of consultations. The majority of consultations are devoted to new families (71%). The mean duration of consultations is 50 minutes, but 40% have a duration of at least 1 hour. Variations of several parameters during the 4 years period were observed and analyzed. Finally, since duration of consultations (more or equal to 1 hour) and personal or family history of breast/ovarian cancer appeared as pivotal elements in our study and consequently may affect the organization of clinics and the structuring as well as the evolution of cancer genetic activity in France, we analyzed more precisely the factors significantly associated with these 2 elements. CONCLUSION: Study compliance was fair (60% of centers) and these results give a good measure of cancer genetic activity in France. The variation of parameters from one year to another may reflect modifications in medical practice (medical orientation rather than research focus and content of cancer genetic clinics) and/or scientific breakthroughs in cancer genetics such as identification of genes predisposing to cancer.

Acute intermittent porphyria: prevalence of mutations in the porphobilinogen deaminase gene in blood donors in France.

OBJECTIVES: Acute intermittent porphyria (AIP) is an autosomal dominant disorder resulting from a 50% deficiency in porphobilinogen deaminase (PBG deaminase). The true prevalence in the general population of mutations in the PBG deaminase gene capable of causing AIP is unknown. However, it is important to identify asymptomatic carriers of AIP mutations because all are at risk to have an acute attack. DESIGN: We measured erythrocyte PBG deaminase from 3350 healthy blood donors. When a clear cut deficiency (< mean minus 2.5 SD) was found, the PBG deaminase gene was analysed by molecular biology technics. SUBJECTS: Four subjects with PBG deaminase deficiency were identified. Two had mutations in the PBG deaminase gene which are known to cause AIP. CONCLUSION: We conclude that, in France, the mutations of the PBG deaminase gene show a high prevalence in the healthy population. If only these two confirmed latent cases are used for the calculation, in France the minimal prevalence of the AIP gene is 1:1675.

Linkage analysis of five fibrillar collagen loci in a large French Marfan syndrome family.

Marfan syndrome consists of a group of dominantly inherited disorders of connective tissue with wide clinical variability. Using the candidate gene approach, we have attempted to map the gene defect in a large French Marfan syndrome family with no ocular manifestations. We performed linkage studies with polymorphic probes for five structural procollagen genes. The data obtained exclude linkage of Marfan syndrome to the two major fibrillar collagen (COL1A1, COL1A2, and COL2A1) genes. These results confirm previously published data obtained from smaller pedigrees. A small positive lod score (Z = 0.99, theta = 0.00) was obtained for the COL3A1-COL5A2 gene cluster located on chromosome 2.

Studies on an isolated West Indies population. III. Epidemiologic study of sensorineural hearing loss.

An epidemiologic study of hearing loss was undertaken on a small Caribbean island and revealed a high frequency of abnormal audiograms among the population of French origin. Since there is no clear-cut discrimination between hypoacusis and normal hearing, but rather a continuous spectrum, the degree of hearing loss was quantified by an audiometric index, using the results of audiograms performed on 70% of the inhabitants. No environmental factors could be identified, although the effect of such factors is highly suggested by several observations of deafness aggravated by, or appearing after, a small dose of ototoxic antibiotics, and also by a strong residual age effect after correction for physiological presbyacusis. Hearing loss was found to be sparsed all over the island. Familial aggregation was noticed for several severe cases.

Studies on an isolated West Indies population: IV. Genetic study of hearing loss.

Hearing troubles were found to be very frequent among inhabitants of French origin in a small Caribbean island. Segregation analysis of hearing loss was performed in 165 complete nuclear families and revealed that familial aggregation could be entirely explained by a single recessive gene with high frequency (0.40). Homozygous individuals for this gene would probably be more susceptible to ototoxic agents than other individuals. High frequency of this gene may be due to a founder effect.

Familial congenital heart disease: how are the various types related?

The distribution of congenital heart lesions was studied in 238 families with at least 2 affected members. A statistical analysis was performed. Concordant lesions were found in 48% of the affected first degree relatives and in 28% of the affected second and third degree relatives. The concordance rate is highly significant for all lesions studied in the first degree relatives, with the exception of ventricular septal defect (VSD). Among the discordant pairs of lesions, some occur significantly more often than expected (tetralogy of Fallot associated with VSD, pulmonary stenosis, and transposition of the great arteries); others, such as the association between VSD and pulmonary stenosis, are significantly less common than would be expected on a random hypothesis. An explanation is proposed suggesting that malformations anatomically dissimilar but resulting from the same heart segment disorder may have some common genes, and that interaction between genes may be responsible for "antagonism" between 2 defects. The embryologic segmental approach to congenital heart disease is reinforced by this genetic study.

An epidemiological and genetic study of facial clefting in France. I. Epidemiology and frequency in relatives.

The frequencies of cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) have been estimated in France to be 0.082% and 0.035%, respectively, after exclusion of malformation syndromes. A genetic and epidemiological study has been carried out on 468 patients with CL(P) and 163 with CP. The results are given in detail and some specific points are discussed: the apparently low incidence in France, the relationship between sex ratio and abortion rates, the maternal effects, and the possibility of an association between CL(P) and CP.

Segregation analysis of congenital glaucoma: approach by two differential models.

To determine the mode of inheritance of congenital glaucoma, segregation analysis was performed using two different models: the transmission probability model and the mixed model. Whereas the latter, testing for monogenic inheritance in the presence of both monogenic and polygenic components, results in strong evidence for a major locus, the former, testing for Mendelian segregation at one locus, rejects this hypothesis. The differences in the results of these two models are discussed and are attributed to the underlying structure of each. Genetic heterogeneity of congenital glucoma is proposed.