Satiety dysfunction in Prader-Willi syndrome demonstrated by fMRI.

The neurobiology relating to the insatiable appetite observed in Prader-Willi syndrome (PWS) has not been fully characterised. Two functional magnetic resonance imaging (fMRI) scans were performed on each of three adults with PWS. The scans were carried out pre- and post-treatment with the antiepileptic topiramate, which had little effect on body weight and appetite in these subjects. Subjects fasted overnight and drank a 75 g dextrose solution prior to fMRI scans for measurement of brain activation levels during/after glucose ingestion. Following glucose administration, there was a significant delay in activation at the hypothalamus and other brain regions associated with satiety compared with previous data on obese volunteers. These regions include the insula, ventromedial prefrontal cortex, and nucleus accumbens. Individuals with PWS showed a mean latency of 24 min while in a previous study obese volunteers had shown a latency of 15 min and lean volunteers a latency of 10 min in the hypothalamus. Our results provide evidence towards a satiety dysfunction in the central nervous system of PWS patients.

Circulating anti-p53 antibodies in esophageal cancer patients are found predominantly in individuals with p53 core domain mutations in their tumors.

Serum antibodies reacting with the tumor suppressor protein p53 have been detected previously in cancer patients with a variety of neoplasms. Two initial (although insufficient) prerequisites for a B-cell response to occur have been proposed: p53 protein accumulation in the tumor or a mutant p53 gene, or both. We have examined 65 esophageal cancer cases (42 from Guangzhou and Shenyang, People's Republic of China, and 23 from Paris, France) to obtain a prevalence estimate of anti-p53 antibodies for this type of cancer and to define the relationship of p53 tumor status to B-cell immune response. Sera were analyzed in a triplicate assay (enzyme-linked immunoassay, immunoprecipitation, and immunoblot) for anti-p53 antibodies. Tumor DNA was screened for mutations in exons 5-8, and tumor tissue was examined by immunohistochemistry for abnormal p53 protein accumulation. p53 mutations were found in 36 (58%) of 62 cases analyzed. Sixteen patients (25%) had circulating antibodies to the tumor suppressor protein. All but two (88%) of the tumors from seropositive cases had a mutation in the DNA binding region of the p53 gene, and with one exception, these tumors also showed nuclear accumulation of the p53 protein. In contrast, tumor mutations were found in just 22 (46%) of the 48 individuals in whom we did not detect anti-p53 antibodies. Among the 22 seronegative cases for which we found no tumor mutations, 11 revealed p53 protein accumulation by immunohistochemical analysis. Thus, circulating anti-p53 antibodies may be present in one-fourth of esophageal cancer patients, most of whom also would be expected to have a p53 gene mutation in their tumors. Patients without such mutations appear considerably less likely to mount a B-cell response to the p53 tumor suppressor protein than those that do (P < 0.01).

[The immunohistochemical study of p53 protein in primary lung cancer].

The expression of tumour suppressor gene P53 products-P53 protein in patients with primary lung cancer has been studied by ABC immunohistochemical method using McAb 1801 as probe. Abnormalities in P53 expression were found in 63 of 78 carcinomas, 23 of 26 squamous cell carcinomas, 23 of 29 adenocarcinomas, 7 of 11 large cell carcinomas, 7 of 9 small cell carcinomas and all 3 cases of adenoid cystic carcinomas showing abnormal P53 expression, whereas no expression of P53 was detectable in 11 normal lung samples. These findings suggest that the pathogenesis of lung cancer may also be related with abnormalities of P53 gene.

Long-term culture of hamster duodenal explants and cells.

Explants from adult Syrian hamster duodenum have been maintained in organ culture on gelatin sponges using CMRL 1066 serum supplemented media for 30 days. There was necrosis of the tall villi architecture during the 1st week in culture while columnar and mucous cells survived, migrated, and replicated along portions of the explant basement membrane and in the gelatin sponge matrix. Cells in the sponge multiplied and formed epithelial sheets which showed villus projections and cyst configurations. The cells in these epithelial structures were attached to one another by junctional complexes. Epithelial cells were isolated from the sponge matrix by collagenase digestion and were successfully grown in culture. These duodenal explants and cells show potential for use as in vitro models for experimental studies, involving acute and chronic response of cells to injury or carcinogen-induced transformation.