PET FDG studies of Wilms tumors

Oral sodium phosphate (NaP) has become an attractive alternative to polyethylene glycol (PEG) for colonic cleansing before colonoscopy, but it potentially has greater complications. This study surveyed members of the Canadian Association of Gastroenterology (CAG) to determine how these colonic lavage agents are used and what complications have been encountered. The Dillman survey technique produced responses from 67% of the 400 members who perform colonoscopy. For the larger out-patient group, respondents used NaP more frequently than PEG (46% versus 35%, respectively, P < 0.015). Respondents used NaP and PEG with similar frequencies for the in-patient group (44% versus 43%). Of respondents using NaP, 45% reported excluding its use in patients with renal failure, 30% with heart disease, 13% with incomplete bowel obstruction and 9% with extreme age. Symptoms suggestive of hypovolemia were reported in 9% of those using NaP compared with 3% using PEG (P < 0.02). Three patients receiving NaP developed acute renal failure. A greater proportion of those using NaP had small unexplained aphthous ulcers (16%) and excessive luminal bubbling (24%) compared with PEG users (3%, P < 0.00001 and 14%, P < 0.03, respectively). These data demonstrate that members of CAG use NaP more frequently than PEG as the colonic lavage solution before colonoscopy. A greater number reported complications with NaP versus PEG, and a significant proportion of the respondents appeared to be unaware of the potential for these complications in specific clinical circumstances.     

Frequent loss of the P16INK4a gene product in human pituitary tumors

Pituitary tumors develop at a high frequency in retinoblastoma (Rb)-knockout mice; however, defects in the Rb gene are not common in human pituitary tumors. The inverse correlation of Rb and p16 defects in certain human tumors has led us to investigate the expression of p16 in human pituitary tumors as an indirect mechanism of Rb inactivation. By Western blot analysis, the p16 gene product was undetectable in 25 human pituitary tumors, whereas high levels of p16 could be demonstrated in 10 normal human pituitary specimens under the same conditions of protein extraction and immunoblotting. Similar results were obtained at the mRNA level with low to undetectable levels of p16 mRNA in 13 of 14 pituitary tumors relative to 5 normal pituitary specimens. Single-strand conformation polymorphism analysis of p16 exons 1 and 2 revealed no mobility shifts in 25 tumors; however, a quantitative differential PCR analysis revealed diminished amplification of p16 relative to a control gene in 3 of 25 tumors, suggesting homozygous p16 gene loss. We conclude that altered expression of the p16 gene product occurs at a high frequency in human pituitary tumors. This altered expression is not associated with frequent p16 mutation or gene loss, suggesting that alternative mechanisms of gene inactivation and/or altered regulation occur in the majority of these tumors.     

Mapping of eight human chromosome 1 orthologs to cattle chromosomes 3 and 16

PTFE-e patches were used in nasal augmentation in 14 patients with a four-year follow-up. This material was chosen because it is inert and biologically compatible with human tissue. None of the patients in which this material was used had intolerance reaction, skin changes, material extrusion, or signs of infection. A review of the world literature showed no cases of poor results with PTFE-e. It is concluded that the best material for nasal augmentation is autologous material, but if not available or difficult to obtain, PTFE-e is the most acceptable synthetic material and produces good results.     

Classification of qh regions in human chromosomes 1, 9, and 16 by C-banding

The occurrance of polyps of the uterine cervix during childhood is described which is exceedingly rare according to the literature. A pediatric gynaecological outpatient department was established two years ago and among about 600 children examined by viginoscopy, nine children with polyps of the cervix were detected. All nine girls had similar symptoms and signs. There was vaginal bleeding with malodorous discharge which could also be characteristic of a malignant tumor. The vaginal introitus was rather larger with an almost absent hymen. It is important to recognize the conditions early and to treat it. The vaginal discharge was treated. The polyp was removed and the base of the polyp was coagulated to avoid a recurrence. It can be expected that polyps of the uterine cervix in childhood will be found more often as the interest in pediatric gynaecology increases.     

Alphoid repetitive DNA in human chromosomes

The thesis describes the first extensive DNA sequence analysis that demonstrated that the tandemly repeated alphoid DNA in the centromere of the human chromosomes consists of distinct subfamilies and in a number equal to or exceeding the number of chromosomes. The expected presence of only one or a few distinct subfamily on individual chromosomes was supported by the characterization of an extremely well-defined subfamily specific for chromosome 7 and represented in the original collection of subfamilies. The pattern of chromosome-specificity breaks down among the acrocentric chromosomes where chromosomes 13 and 21 were found to share one and chromosomes 14 and 22 to share another specific subfamily. By in situ hybridization these subfamilies were shown not to be shared by other chromosomes. The remarkable pairwise pattern of sequence homogenization was present also in the chimpanzee genome raising the question of its biological role. However, the subfamilies on these human and chimpanzee chromosomes are not orthologous but were shown to originate from two evolutionarily different repeat families. It follows that dramatic sequence evolution has occurred in one or both species during or after separation. The sequence evolution might even occur at a higher rate in humans. This possibility was studied in orthologous alphoid sequences on the X chromosome of humans and the great apes. The analysis supports the general view that our closest relative is the chimpanzee and indicates that the rate of recombination is increased in the human repeat DNA. A "molecular clock" running faster in this DNA may have evolutionary implications. Finally, the usefulness of alphoid subfamilies as chromosome-specific markers is illustrated in a cytogenetic dissection of the centromeric region of Robertsonian translocations. The breakpoints were located to satellite III DNA leaving these chromosomes dicentric. The order of the different tandem DNAs on the p-arm of the acrocentric chromosomes could also be established.     

Study of C-polymorphisms of chromosomes 1, 9 and 16 in lymphocytes of patients with laryngeal carcinoma

A case-control study of the C-bands of #1, 9 and 16 was performed on PHA-stimulated lymphocytes in 29 individuals, 16 of whom with laryngeal carcinoma. C-bands were revealed using Sumner's CBG staining technique. The assay for chromosomic markers was performed using traditional measuring methods and an image analysis system. The calculation of the heterochromatic index (HI) using Neeley's method was chosen to evaluate size heteromorphisms and was used for each homologue of chromosome pairs examined. No significant difference was found between patients and controls with regard to size polymorphisms. The comparison between patients and controls was significant when size polymorphisms at the level of #9 were taken into account. In fact, 9 out of 16 patients (56%) versus 2 out of 13 controls (15%) presented a partial pericentric inversion on one of the two homologues of chromosome pair 9 (chi 2 = 5.325; 0.05 > p > 0.01). The two measuring techniques produced broadly similar results. However, in our opinion, the classic method is preferable owing to its simplicity of use. In conclusion, we affirm that pericentric inversion of #9 may be regarded as a predisposing factor for the onset of laryngeal carcinoma whose manifestation is triggered by tobacco and alcohol consumption.     

Localization of human midisatellite and macrosatellite DNA sequences on chromosomes 1 and X in the great apes

We report the case of a 38-year-old man who, 2 weeks after a laparoscopic Nissen fundoplication, was referred to our Unit because of acute wrap herniation and intrathoracic gastric perforation. Although both of these complications have already been described, this is the first case in which they have occurred simultaneously and not as an immediate consequence of the operation. Intraoperative findings suggested that diaphragmatic crura had not been reapproximated and that the gastric wrap had not been fixed to them. This observation and the fact that immediately after hospital discharge the patient had sustained intense physical efforts can explain acute wrap herniation. Placement of full-thickness sutures may account for gastric perforation. These pathogenetic determinants and their preventive measures are discussed in the light of a review of the literature.     

The terminal DNA structure of mammalian chromosomes

In virtually all eukaryotic organisms, telomeric DNA is composed of a variable number of short direct repeats. While the primary sequence of telomeric repeats has been determined for a great variety of species, the actual physical DNA structure at the ends of a bona fide metazoan chromosome with a centromere is unknown. It is shown here that an overhang of the strand forming the 3' ends of the chromosomes, the G-rich strand, is found at mammalian chromosome ends. Moreover, on at least some telomeres, the overhangs are > or = 45 bases long. Such surprisingly long overhangs were present on chromosomes derived from fully transformed tissue culture cells and normal G0-arrested peripheral leukocytes. Thus, irrespective of whether the cells were actively dividing or arrested, a very similar terminal DNA arrangement was found. These data suggest that the ends of mammalian and possibly all vertebrate chromosomes consist of an overhang of the G-rich strand and that these overhangs may be considerably larger than previously anticipated.     

Retrotransposon-related DNA sequences in the centromeres of grass chromosomes

Several distinct DNA fragments were subcloned from a sorghum (Sorghum bicolor) bacterial artificial chromosome clone 13I16 that was derived from a centromere. Three fragments showed significant sequence identity to either Ty3/gypsy- or Ty1/copia-like retrotransposons. Fluorescence in situ hybridization (FISH) analysis revealed that the Ty1/copia-related DNA sequences are not specific to the centromeric regions. However, the Ty3/gypsy-related sequences were present exclusively in the centromeres of all sorghum chromosomes. FISH and gel-blot hybridization showed that these sequences are also conserved in the centromeric regions of all species within Gramineae. Thus, we report a new retrotransposon that is conserved in specific chromosomal regions of distantly related eukaryotic species. We propose that the Ty3/gypsy-like retrotransposons in the grass centromeres may be ancient insertions and are likely to have been amplified during centromere evolution. The possible role of centromeric retrotransposons in plant centromere function is discussed.     

Frequent loss of p16 expression and its correlation with clinicopathological parameters in pancreatic carcinoma

Expression of the p16 gene product in human primary pancreatic carcinoma (PC) was investigated in paraffin-embedded tissue using a monoclonal antibody against p16 protein, clone G175-405, by means of immunohistochemistry, and the correlation of results with various clinicopathological parameters was evaluated. All six cases of normal pancreas and all but 1 of 20 cases of chronic pancreatitis expressed p16 protein, whereas 37.5% (3 of 8) of cystadenomas and 41. 9% (26 of 62) of PCs lost p16 expression. There was a significant difference between chronic pancreatitis and PC for frequency of the loss of p16 expression (P < 0.01). Moreover, loss of p16 expression in pancreatic malignancy was significantly associated with histological grade (G1 versus G2 and G3, P < 0.01) but not with sex, age, clinical stage, tumor location, or resectability. The survival period was shorter and metastasis is more likely in those cases that did not show p16 expression than those that did.     

An important subgroup of phyllodes tumors of the breast is characterized by rearrangements of chromosomes 1q and 10q

From a study of 10 cases of our own and 13 cases of the literature, anomalies of chromosome 1q and 10q emerge as consistently occurring changes in an important subgroup of phyllodes tumors of the breast. Anomalies of chromosome 1 were the most frequent ones, with a gain of 1q material, and histologically the tumors in which these anomalies were found were low grade malignancies. Structural changes of 10q emerged as the second most frequent chromosome change.     

Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16

Benign infantile familial convulsions is an autosomal dominant disorder characterized by nonfebrile seizures, with the first attack occurring at age 3-12 mo. It is one of the rare forms of epilepsy that are inherited as monogenic Mendelian traits, thus providing a powerful tool for mapping genes involved in epileptic syndromes. Paroxysmal choreoathetosis is an involuntary-movement disorder characterized by attacks that occur spontaneously or are induced by a variety of stimuli. Classification is still elusive, and the epileptic nature of this movement disorder has long been discussed and remains controversial. We have studied four families from northwestern France in which benign infantile convulsions was inherited as an autosomal dominant trait together with variably expressed paroxysmal choreoathetosis. The human genome was screened with microsatellite markers regularly spaced, and strong evidence of linkage for the disease gene was obtained in the pericentromeric region of chromosome 16, with a maximum two-point LOD score, for D16S3133, of 6.76 at a recombination fraction of 0. Critical recombinants narrowed the region of interest to a 10-cM interval around the centromere. Our study provides the first genetic evidence for a common basis of convulsive and choreoathetotic disorders and will help in the understanding and classification of paroxysmal neurological syndromes.     

Proportionate representation of rDNA and Balbiani ring DNA in polytene chromosomes of Chironomus tentans

Thrombin is known to reduce the K+ content of human platelets, but the subcellular origin of the lost K+ is not known. The effect of aggregating agents on K+ release was studied in platelets labeled in plasma by preincubation with 42KCI. Platelets were separated from plasma by gel filtration through Sepharose 2B equilibrated with K+ -free Tyrode's buffer. Platelet K+ was 116nEq/10(8) platelets, of which 23% was found to be extracellular immediately after gel filtration. K+ influx was 65 nEq/10(8) platelets/hr at pH 7.5 and was more rapid at pH 7.9. About 70% of cell K+ exchanged with plasma in 4 hr with first-order kinetics, while a minor fraction of about 30% exchanged with a slower time course. This slowly exchanging fraction of platelet K+ was thought to arise from heterogeneity in the platelet population. Epinephrine and ADP aggregated gel-filtered platelets and released serotonin, but with loss of only 5%-10% of cell K+ and no beta-glucuronidase. In contrast, thrombin released up to 30% of platelet K+, whether aggregation occurred or was prevented by not stirring the cells. The specific activity of K+ released by all aggregating agents was identical to the specific activity of total platelet K+. Thrombin (0.01-0.2 NIH U/ml) released serotonin and also beta-glucuronidase (an enzyme of the alpha-granule), and there was a linear relation between release of K+ and this enzyme (r = 0.88). No lysis of platelets occurred, since lactic dehydrogenase was not detected. Pretreatment of platelets with aspirin in vitro inhibited thrombin-induced release of serotonin but had no effect on the loss of K+ or beta-glucuronidase. In contrast, the ingestion of aspirin by mouth inhibited the release of serotonin, beta-glucuronidase, and K+ by thrombin. The data suggested that the K+ loss induced by thrombin was primarily derived from release of alpha-granules and that these organelles contained about 20% of the total platelet K+ in a freely exchangeable and nonsequestered state.