ABSTRACT
BACKGROUND: Adrenal ganglioneuroma (GN) is seldom considered in the differential diagnosis of adrenal lesions, and its clinical presentation is not well known. OBJECTIVE: Our aim was to describe the clinical, biochemical, and radiological features of adrenal GNs in adults. METHODS: Seven adults underwent endocrine investigation for adrenal lesions that were confirmed to be adrenal GNs. RESULTS: Mean age of the seven patients was 49 yr (range, 23 to 71 yr). Average tumor diameter was 5.0 cm (range, 1.5 to 10.4 cm). In five patients, the adrenal lesions were found incidentally. A 49-yr-old female carried a germline mutation in MSH2 gene. A 57-yr-old female presented with mild virilization and increased testosterone levels. Bilateral adrenal venous sampling revealed testosterone production from her right adrenal lesion. All tumors showed nonenhanced attenuation between 25 and 40 Hounsfield units on computed tomography scan. Magnetic resonance imaging revealed low- to iso-signal intensity on T1-weighted imaging and high-signal intensity on T2-weighted imaging. [(18)F]-2-Fluoro-deoxy-d-glucose-positron emission tomography scan (n = 5) disclosed a mean standard uptake value of 2.4. Three tumors were composite pheochromocytoma-GN. Microsatellite instability study and immunohistochemical analysis of MSH2 protein in a patient carrying a MSH2 mutation showed normal MSH2 protein expression and low microsatellite instability, indicating that the adrenal GN was not related to the patient's MSH2 germline defect. CONCLUSIONS: We describe one of the largest series of adult adrenal GNs. Adrenal GNs may secrete testosterone or be part of a composite tumor with pheochromocytoma. The association of adrenal GN with MSH2 mutation seems to be a coincidental finding.
Subject(s)
Adrenal Gland Neoplasms/pathology , Adrenal Glands/pathology , Ganglioneuroma/pathology , Pheochromocytoma/pathology , Adaptor Proteins, Signal Transducing/metabolism , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/metabolism , Adrenal Glands/diagnostic imaging , Adrenal Glands/metabolism , Adult , Aged , Diagnosis, Differential , Female , Ganglioneuroma/diagnostic imaging , Ganglioneuroma/metabolism , Humans , Immunohistochemistry , Incidental Findings , Magnetic Resonance Imaging , Male , Microsatellite Instability , Middle Aged , MutL Protein Homolog 1 , MutL Proteins , Neoplasm Proteins/metabolism , Nuclear Proteins/metabolism , Pheochromocytoma/diagnostic imaging , Pheochromocytoma/metabolism , RadiographyABSTRACT
In many haematological diseases, and more particularly in B-cell chronic lymphocytic leukaemia (B-CLL), the existence of a tumour suppressor gene located within the frequently deleted region 13q14.3, has been put forward. A wide candidate region spanning from marker D13S273 to D13S25 has been proposed and an extensive physical map has been constructed by several teams. In this study, we sequenced a minimal core deleted region that we have previously defined and annotated it with flanking available public sequences. Our analysis shows that this region is gene-poor. Furthermore, our work allowed us to identify new alternative transcripts, spanning core regions, of the previously defined candidate genes DLEU1 and DLEU2. Since their putative involvement in B-CLL was controversial, our present study provide support for reconsidering the DLEU1 and DLEU2 genes as B-CLL candidate genes, with a new definition of their organisation and context.
Subject(s)
B-Lymphocytes/metabolism , Genes, Tumor Suppressor , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Sequence Deletion/genetics , Alternative Splicing/genetics , Base Sequence , Chromosome Mapping , Databases, Nucleic Acid , Exons/genetics , Expressed Sequence Tags , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Repetitive Sequences, Nucleic Acid/genetics , Sequence Analysis, DNAABSTRACT
This study examines a population of spouse abusers undertaking a treatment program. Its purpose was to identify the variables associated with dropout and completion of treatment and to build a predictive model. Data were collected on 286 men who began group treatment in one of eight community programs in the province of Quebec, Canada. Results show that men who complete treatment are older, better educated and have better economic conditions than men who drop out. They also have a more stable family life, have been in a relationship for a longer period of time and have more children with their actual spouse. Men who completed treatment showed more commitment, better working capacities and a higher level of agreement with their therapists, thus developing a stronger therapeutic alliance. Support provided by people in the environment was significantly related to treatment completion. Social and judicial pressures were not related to completion.
Subject(s)
Patient Dropouts/psychology , Psychotherapy, Group , Spouse Abuse/rehabilitation , Adult , Age Factors , Educational Status , Female , Humans , Male , Quebec , Social Support , Socioeconomic Factors , Spouse Abuse/prevention & control , Spouse Abuse/psychologyABSTRACT
Deletion of the 13q14 chromosomal region is frequent in B cell chronic lymphocytic leukemia (B-CLL) and is believed to inactivate a tumor supressor gene (TSG) next to RB1. We studied microsatellite markers spanning the 13q14 chromosomal region in 138 children with acute lymphoblastic leukemia (ALL). Allelic loss was demonstrated in six cases (4.3%). Deletion did not include RB1 in two cases. In five patients, the deleted region overlapped that described in B-CLL. A sixth patient harbored a smaller deletion, slightly more telomeric than minimal deleted regions reported in B-CLL. Apparent differences in the delineation of the minimal deleted region could be due to the fact that the putative TSG is a very large gene, with some deletions affecting only a part of it. Our present findings suggest that at least some of its exons lie within a region of less than 100 kb more telomeric that previously thought.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 13 , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Base Sequence , Child , Child, Preschool , DNA Primers , Genotype , Humans , In Situ Hybridization, Fluorescence , Infant , Polymerase Chain ReactionABSTRACT
The chromosomal region 13q14.3 is frequently deleted in B cell chronic lymphocytic leukemia (B-CLL) and it is supposed that a tumor suppressor gene, involved in this leukemogenesis, is located in this area. The first exons of two genes, Leu1 and Leu2, mapped in a minimally deleted 13q14.3 region, are systematically lost in B-CLL sharing a 13q14.3 deletion. These two genes have been proposed as strong tumor suppressor gene candidates. However, in a study on 15 13q14.3 deleted B-CLL, we found three patients in which this critical region was not involved. Because of these results and that no mutations were detected on the two genes in a previous study, we think that Leu1 and Leu2 can be excluded as tumor suppressor genes.
Subject(s)
CD5 Antigens/genetics , CD8 Antigens/genetics , Chromosome Deletion , Chromosomes, Human, Pair 13 , Genes, Tumor Suppressor , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Humans , Loss of Heterozygosity , Polymerase Chain ReactionABSTRACT
We report the characterization of a new gene mapped at chromosome band 13q14.3 telomeric to the retinoblastoma gene. This gene, designated CHC1L (for chromosome condensation 1-like), is composed of 14 exons spanning 30 kb of genomic DNA and encodes a ubiquitously expressed 3-kb mRNA. The N-terminal half of the deduced amino acid sequence shows strong homology with the seven tandem repeat structure of the regulator of chromosome condensation RCC1, which acts as a guanine nucleotide exchange factor (GEF) protein for the Ras-related GTPase Ran. CHC1L appears to be a new member of the RCC1-related GEF family.
Subject(s)
Cloning, Molecular , Proteins/genetics , Amino Acid Sequence , Base Sequence , Chromosome Mapping , Chromosomes, Human, Pair 13/genetics , DNA, Complementary , Guanine Nucleotide Exchange Factors , Humans , Molecular Sequence Data , Proteins/chemistry , Proteins/metabolism , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Tumor Cells, Cultured , ras Guanine Nucleotide Exchange FactorsABSTRACT
An expression map containing 48 ESTs was constructed to identify a tumor-suppressor gene involved in B-cell chronic lymphocytic leukemia (B-CLL), which was previously assigned to chromosome band 13q14.3 close to genetic markers D13S25 and D13S319. Thirty-nine of these 48 ESTs, together with 11 additional ones listed in databases, were initially assigned to chromosome 13q14 between markers D13S168 and D13S176. Nine others have recently been located in the D13S319 region. Our results indicate that 48 of the 59 ESTs analyzed belong to a YAC contig of chromosome 13 band q14, and 22 are contained on YAC 933e9, which encompasses the B-CLL critical region. Ten of these 22 ESTs were accurately assigned on a PAC, BAC, and cosmid contig encompassing the smallest minimal deletion area described so far in B-CLL, and 20 were tested for their expression on 27 normal or tumor tissues. One EST appears to be a likely candidate for the tumor-suppressor gene involved in B-CLL.
Subject(s)
Chromosomes, Human, Pair 13/genetics , Gene Expression Regulation, Neoplastic/genetics , Genes, Tumor Suppressor/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Chromosome Mapping , Chromosomes, Artificial, Yeast/genetics , Databases, Factual , Expressed Sequence Tags , Humans , RNA, Messenger/genetics , Sequence Deletion/geneticsABSTRACT
A putative tumor suppressor gene involved in B cell chronic lymphocytic leukemia (B-CLL) was mapped to human chromosome 13q14.3 close to the genetic markers D13S25 and D13S319. We constructed a 780-kb-long contig composed of cosmids, bacterial artificial chromosomes, and bacteriophage P1-derived artificial chromosomes that provides essential information and tools for the positional cloning of this gene. The conting contains both flanking markers as well as several additional genetic markers, three ESTs, and one potential CpG island. In addition, using one B-CLL patient, we characterized a small internal deleted region of 550 kb. Comparing this deletion with other recently published deletions narrows the minimally deleted area to less than 100 kb in our physical map. This deletion core region should contain all or part of the disrupted in B cell malignancies tumor suppressor gene.
Subject(s)
Chromosomes, Human, Pair 13 , Cosmids/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Sequence Deletion , Bacteriophages/genetics , Chromosomes, Artificial, Yeast , Chromosomes, Bacterial , Genetic Markers , Heterozygote , Humans , In Situ Hybridization, Fluorescence , Sequence Tagged SitesABSTRACT
: This research, which was carried out in the spring of 1989 and 1990 in seven balsam fir (Abies balsamea) plantations in southeastern Quebec, examines potential deleterious effects of three insecticides (i.e. dimethoate, diazinon and insecticidal soap) on breeding American Robins (Turdus migratorius) (n=87 nests) and Song Sparrows (Melospizsa melodia) (n=41 nests). Through analyses of blood serum cholinesterases (AChE and BChE) activity both prior to and the second day following applications of the two organophosphorus insecticides, we showed that adult American Robins, Song Sparrows and Chipping Sparrows (Spizella passerina) breeding in the treated plantations were exposed to diazinon and dimethoate (p<0.05). Signs of exposure to diazinon (p<0.05) were also found in young American Robins. However, despite sharp reductions in blood ChE (and, in some cases, marked inhibition confirmed by 2-PAM reactivation), no cases of adult mortality were recorded following the treatments. Cases of complete or partial mortality were recorded in American Robin and Song Sparrow nests, even among control birds (non-exposed birds). No mortality was recorded for broods exposed to the insecticidal soap. Abandonment of nests and egg infertility were ruled out as possible causes of mortality. The cases of total mortality observed in American Robin and Song Sparrow broods exposed to dimethoate were similar to those recorded for control nests (18 and 25% compared to 14 and 21%, respectively). However, among American Robin and Song Sparrow nestlings exposed to diazinon, essentially twice as many cases of total mortality (31 and 38%, respectively) were recorded as for the control nests. It appears that American Robin eggs are sensitive to diazinon and dimethoate, particularly when spraying is carried out early in the incubation stage. In the case of the Song Sparrow, it is mainly the nestlings that succumb after diazinon is sprayed on them or when dimethoate applications are made during the egg stage.