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C Sapienza

Publications and source records attributed to C Sapienza.

At least 19 recordsLinked to original sources
PubMed1994

Articulatory, developmental, and gender effects on measures of fundamental frequency and jitter.

Fundamental frequency (Fo) and jitter were measured in digitized live-voice productions of sustained vowels [a], [i], and [u] from women, men, and 6- through 9-year-old children. Results showed (a) significant developmental differences for mean Fo and for the pattern of jitter by vowel type, (b) significant gender differences in Fo and jitter only for adults, (c) significant differences in Fo and jitter according to vowel type for all subjects, and (d) similar amounts of mean absolute jitter for children and women for all vowels with nonsignificantly different values of jitter for boys and men on [i] and [u] productions. Results are related to Honda's theory of intrinsic Fo for vowels and to Titze's neurologic model of jitter.

Adult↗
PubMed1994

Preferential amplification of the paternal allele in neuroblastomas with N-myc amplification.

There is increasing evidence that imprinting plays an important role in influencing the parental origin of genes involved in cancer-specific rearrangements. In advanced stage neuroblastomas, both allelic loss of the short arm of chromosome 1 (1p) and amplification of the proto-oncogene N-myc are often seen. Therefore, we analyzed 22 human neuroblastomas with N-myc amplification to determine the parental origin of the N-myc allele that is amplified and the 1p allele that is deleted. We used at least three polymorphisms for both the 1p and the N-myc locus to analyze blood and tumor samples from neuroblastoma patients, as well as blood samples from their parents. We determined that the paternal allele of N-myc was amplified in 12 of 15 informative cases (P = 0.02), and the paternal allele on 1p was lost in 6 of 11 informative cases (P > 0.2). These results suggest that parental imprinting does not appear to affect the 1p allele that is deleted, at least in the cases that we have examined. However, imprinting has an important influence on determining the N-myc allele that is amplified in these tumors, suggesting that the paternal allele is either more highly expressed or more likely to undergo amplification.

Alleles↗
PubMed1994

The genetics of retinoblastoma, revisited.

Our epidemiological and genetic analyses of sporadic and familial retinoblastoma indicate that an X-chromosome-linked gene is involved in the genesis of a significant fraction of new bilateral cases of the disease. The activity of this gene results in sex-ratio distortion in favor of males among patients with bilateral sporadic disease. Among the offspring of these males, both sex-ratio distortion in favor of males and transmission-ratio distortion in favor of affecteds are observed. We propose that these phenomena are due to the inability of these males to erase the genome imprint established on the half of the genome inherited from their mothers.

Female↗
PubMed1993

Preferential amplification of the paternal allele of the N-myc gene in human neuroblastomas.

Genomic imprinting plays a role in influencing the parental origin of genes involved in cancer-specific rearrangements. We have analysed 22 neuroblastomas with N-myc amplification to determine the parental origin of the amplified N-myc allele and the allele that is deleted from chromosome 1p. We analysed DNA from neuroblastoma patients and their parents, using four polymorphisms for 1p and three for the N-myc amplicon. We determined that the paternal allele of N-myc was preferentially amplified (12 out of 13 cases; P = 0.002). However, the paternal allele was lost from 1p in six out of ten cases, consistent with a random distribution (P > 0.2). These results suggest that parental imprinting influences which N-myc allele is amplified in neuroblastomas, but it does not appear to affect the 1p allele that is deleted in the cases that we have examined.

Adrenal Gland Neoplasms↗
PubMed1993

Respiratory and laryngeal measures of children during vocal intensity variation.

Simultaneous aerodynamic, acoustic, and kinematic measurements from the laryngeal and respiratory systems were made in order to study mechanisms for changing vocal intensity. Aerodynamic and acoustic measures include an approximation of open quotient, maximum flow declination rate, alternating glottal airflow, estimated tracheal pressure, sound pressure level, and fundamental frequency. Respiratory measures included lung volume, rib cage, and abdominal displacements. Adults were used as a comparison group to twenty 4-year-olds and twenty 8-year-olds. Laryngeal and respiratory results indicate that speech production differences between the children and adults are based both on size and function. For example, children's absolute anteroposterior diameters of the rib cage are smaller than adults, but their rib cage movement is larger and encompasses a different range during speech breathing. Since children are functionally different than adults, age specific speech production models need to be developed.

Adult↗
PubMed1992

Loss of heterozygosity for chromosomes 1 or 14 defines subsets of advanced neuroblastomas.

Neuroblastomas have been characterized genetically by N-myc amplification and by deletions or loss of heterozygosity (LOH) for the short arm of chromosome 1. However, recent studies have suggested deletion or allelic loss involving at least three other chromosome arms, 11q, 14q, and 17p. Therefore, we undertook an analysis of allelic loss for these respective chromosomal arms to determine the frequency and pattern of LOH as well as the correlation of these findings with other biological and clinical variables. A group of 24 pairs of normal and tumor DNAs was chosen that were representative of patients of different ages and stages. A substantial frequency of LOH (greater than or equal to 20%) was found only for 1p and 14q, whereas LOH for the other chromosome arms occurred in less than or equal to 5% of cases. On the basis of these results, we extended the analysis to a total of 59 neuroblastomas, and we found 1p LOH in 15 of the 59 cases (25%) and 14q LOH in 10 of 43 informative cases (23%). N-myc amplification was found in 15 of the 59 cases (25%). This analysis confirmed that 1p LOH and 14q LOH occurred almost exclusively in patients with advanced stages of disease. Furthermore, LOH for 1p and 14q usually occurred independent of each other, and 1p LOH frequently was associated with N-myc amplification, whereas 14q LOH was not. Thus, our results demonstrate that neuroblastomas are complex genetically and that there are at least two distinct loci for putative suppressor genes that are deleted independently in this tumor, both of which are associated with advanced stages of disease.

Blotting, Southern↗
PubMed1992

A reliable method for the use of oligonucleotides as probes in blot-hybridization experiments.

We have developed a ligation and specific-primer radiolabeling method that allows the use of oligonucleotides as probes in blot-hybridization experiments. The major advantage of the protocol is that standard hybridization and washing conditions may be used and yield high signals and low background. The observed increase in the stability and intensity of the hybridization signals appears to result from both increased length and specific radioactivity of the hybridization probe.

Base Sequence↗
PubMed1992

The polar-lethal Ovum mutant gene maps to the distal portion of mouse chromosome 11.

Genome imprinting is the process by which identical alleles at a particular locus may be rendered functionally different depending on the sex of the parent contributing the allele. While several mutations in imprinted genes have been defined, no variants in the regulatory system that gives rise to imprinting have been described. Here we report our genetic analysis of the behavior of the interstrain, polar, embryonic-lethal phenotype known as the "DDK syndrome." We have mapped the interstrain, polar-lethal region of the genome to the distal portion of mouse chromosome 11, near the Xmv-42 locus. We propose that the lethal phenotype is not caused by a standard mutation, but by aberrant imprinting of a gene within this region.

Animals↗
PubMed1992

Genome imprinting and cancer genetics.

Parent-of-origin-dependent modification of the genome (genome imprinting) is thought to be involved in the formation of several types of human cancer. Simple modifications of Knudson's two-hit model give rise to two types of predictions with respect to the genetic behavior of such diseases. In the first, rare alleles of modifier genes will give rise to the retention of the same parent's tumor suppressor alleles in sporadic cases. In the second, other variants of the modifier genes will result in failure to establish linkage between tumor suppressor genes and disease predisposition in familial cases. Both of these predictions are fulfilled by experiment. Additional modifications of existing models are predicted to result in more complex patterns of inheritance. The demonstration of such patterns in human pedigrees will require an extremely sophisticated level of genetic analysis.

Genome, Human↗
PubMed1991

Genome imprinting and carcinogenesis.

The preferential retention of paternal tumor suppressor alleles in sporadic tumors and the failure to demonstrate genetic linkage between disease predisposition and tumor suppressor loci in familial cases indicates that genome imprinting may be involved in the genesis of some pediatric cancers. A genetic model that invokes the activity of modifier loci (imprinting genes) on alleles to be modified (imprinted genes) is able to account for these data. Genome imprinting may be viewed as a special case of dominance modification, differing from other examples only in that the modification of dominance is dependent on gamete-of-origin. Data from human pediatric tumors, transgenes in the mouse and variegating position-effects in Drosophila, indicate that the net effect of modifier loci is the inactivation of alleles at affected loci. Polymorphism at the level of the modifier loci will result in different degrees of modification between individuals. With respect to tumors, the most important mechanism by which these differences are manifested is cellular mosaicism for the expression of a modified allele. Such characteristics are reminiscent of the behavior of variegating position-effects in Drosophila and the application of this paradigm to human disease phenotypes provides both a mechanism by which differential genome imprinting may be accomplished as well as genetic models that may explain the clinical association of syntenic diseases, the association between tumor progression and specific chromosomal aneuploidy and the unusual inheritance characteristics of many diseases.

Alleles↗
PubMed1990

Sex-linked dosage-sensitive modifiers as imprinting genes.

It is proposed that differential genome imprinting is the result of dosage-sensitive modifier genes located on the sex chromosomes. Parallels between variegating position-effects in Drosophila, the phenotype elicited by transgenes in the mouse and data from several pediatric tumors indicate that the net result of the activity of such modifier genes is often cellular mosaicism in the expression of affected alleles. The mechanism by which inactivation of affected alleles is achieved is proposed to be through the formation of heterochromatic domains. Because the relevant sex-linked modifying loci are dosage sensitive in their activity, differential imprinting will occur even within homogeneous genetic backgrounds. The presence of allelic variants at these loci in non-inbred populations will give rise to variation in the observed expressivity and mode of inheritance of affected traits.

Animals↗
PubMed1989

A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting.

Embryonal rhabdomyosarcomas (malignant pediatric tumors of striated muscle origin) have been shown to arise from cells that are clonally isodisomic for loci on chromosome 11p. We determined the parental origin of alleles in this genomic region in familial and sporadic cases of this disease and found that isodisomic chromosome 11p alleles in each tumor were of paternal origin. We have developed a modification of Knudson's two-hit model from these data that is capable of explaining the preferential allele retention and of resolving the apparent contradiction between such specific and early events in several embryonal tumors and discrepancies in the inheritance of predisposition in some of these diseases.

Alleles↗