Analysis of somatostatin receptor subtype mRNA expression in human breast cancer.

Somatostatin is a widely distributed inhibitory peptide with growth-inhibitory effects in several human tumours, including breast cancer, raising the possibility that it may have therapeutic potential. The effects of somatostatin are mediated via a family of cell-surface receptors that differ in their tissue distribution, pharmacological properties and intracellular response mediators, suggesting that they mediate different functions of the peptide. We have analysed the expression of somatostatin receptor subtype (SSTR1-5) mRNA in normal and malignant breast tissue.

Epstein-Barr virus nuclear antigen (EBNA)3C is an immortalizing oncoprotein with similar properties to adenovirus E1A and papillomavirus E7.

Epstein-Barr virus (EBV) requires six genes to efficiently immortalize human B cells. We have shown that one of these, EBNA3C, can cooperate with activated (Ha-)ras in co-transfection assays to immortalize and transform rat embryo fibroblasts (REFs). EBNA3C also augmented transformation by (Ha-)ras and a mutant p53 to a similar extent as human papilloma virus E7.

Acute transverse myelitis associated with Chlamydia psittaci infection.

We report a case of transverse myelitis presenting with fever and rapidly deteriorating neurological signs associated with Chlamydia psittaci infection. It resolved with no long-standing neurological consequences. Only one previous report has described transverse myelitis in association with psittacosis, and this resulted in permanent neurological sequelae.

Sensitivity of p53 lysine mutants to ubiquitin-directed degradation targeted by human papillomavirus E6.

The activity of the p53 tumor suppressor protein is regulated, at least in part, through the stability of the protein. p53 degradation in normal cells is controlled by ubiquitin-dependent proteolysis, and activation of p53 following DNA damage is associated with an increase in the stability of the protein. The human papillomavirus-encoded E6 protein abrogates p53 function by targeting it for rapid degradation, also through the ubiquitin pathway.

Development of delta-opioid receptor subtypes and the regulatory role of weaning: radioligand binding, autoradiography and in situ hybridization studies.

Evidence from behavioral studies suggests that the process of weaning activates the development of a delta-opioid receptor subtype. We now report the influence of weaning on the development of delta receptors in the central nervous system assessed by membrane homogenate binding and autoradiography with selective delta radioligands and by in situ hybridization using a cRNA probe for the delta receptor. Binding was carried out by using [3H][D-Ala2]deltorphin I (DELT I), [3H]IIe5,6-deltorphin II (IIe5,6-DELT II) and [3H]naltrindole (NTI).

Viral infection and cancer.

Infection with specific viruses has a role in the pathogenesis of some cancers in human beings. However, the incidence of such cancers is much lower than the frequency of virus infection, suggesting either that infection alone does not result in cancer and that cellular events in addition to the presence of the virus must occur, or that cancer occurs only if viral proteins are expressed in an appropriate cell type or in an immunocompromised host. Molecular analysis of viruses found in association with cancer has revealed that they function, at least in part, by encoding proteins which can associate with and subvert the function of host cell-encoded tumour suppressor proteins which regulate pathways of growth arrest and apoptosis.

Aging and memory: corrections for age, sex and education for three widely used memory tests.

The associate learning subtest from the Wechsler Memory Scale; Benton's Visual Retention test and a Controlled Word Association Task (FAS) were administered to a random sample of normal, healthy individuals whose age ranged from 20 to 79 years, recruited within the Italian peninsula. The neuropsychological examination took place on a mobile unit and the tests were given by the same team of neuropsychologists to reduce variability among examiners. The Research Project was known as Progetto Memoria.

Transcriptional activation by p53 correlates with suppression of growth but not transformation.

The tumor suppressor protein p53 shows growth and transformation suppression functions that are frequently lost by mutant proteins detected in cancers. Using a large series of p53 mutants, we have demonstrated an excellent correlation between transcriptional activation and growth suppression in p53-null human cells. Not all transcriptionally active mutants retain the ability to suppress transformation in primary rodent cells, however, and two tumor-derived point mutants displayed some evidence of both transforming and transactivating activity.

Detergent extraction and enzymatic analysis for fecal long-chain fatty acids, triglycerides, and cholesterol.

We report a procedure for determining fecal long-chain fatty acids (LCFA), triglycerides, and cholesterol after detergent extraction with 10 mL/L Triton X-100, 6 mL/L Brij 30, and 0.1 mol/L HCl in isotonic saline by enzymatic analysis of the extraction supernates. Mean recoveries of calibrators ranged from 105% to 117%.

Structure of everyday memory in adults with Age-Associated Memory Impairment.

Everyday memory was tested in a group of adults manifesting Age-Associated Memory Impairment; a computerized battery of tests was constructed to simulate memory tasks of daily life. Confirmatory and other structural equation models were estimated for the entire sample of 273 Ss and for 3 age groups. A 4-factor model was found to fit the data well and was invariant across age and gender.

Interaction of p53 with MDM2 is independent of E6 and does not mediate wild type transformation suppressor function.

Using a new series of p53 mutants targeting the conserved regions we have analysed the relationship of various activities of the protein. Mdm-2 and human papillomavirus (HPV) E6, two proteins which interact with and abrogate p53 function, were shown to bind independently. Deletion of the conserved regions of the protein in which most of the naturally occurring mutations are found (boxes II-V) abrogated transcriptional activity and the ability to interact with E6, supporting the importance of this DNA binding domain to these activities.

Posttransplant skin cancer: a possible role for p53 gene mutation but not for oncogenic human papillomaviruses.

Background: Loss of p53 tumor suppressor function is a critical step in the development of diverse malignancies, including skin cancers in nonimmunosuppressed patients where UV-specific p53 gene mutations have been identified. In tumors associated with human papillomavirus (HPV), such as cervical carcinoma, p53 may be inactivated instead by binding to a viral oncoprotein.

Objective: Our purpose was to examine the hypothesis that HPV may play an analogous role in the development of posttransplant skin cancer.

Modulation of transcriptional regulatory properties of p53 by HPV E6.

The E6 protein encoded by human papillomavirus type 16 (HPV16), a genital virus with oncogenic potential, can target cellular p53 for rapid degradation following the formation of a complex including the two proteins. Some studies suggest that the E6 proteins encoded by HPV6 and 11, viral types which are normally limited to benign lesions, may also interact with p53, although the association is weaker than that seen with HPV16 E6. The present study demonstrates that E6 proteins from HPV16 and HPV6 can modulate the transcriptional regulatory functions of p53 in several cell types.

Evidence that weaning stimulates the developmental expression of a delta-opioid receptor subtype in the rat.

To study whether weaning stimulates the development of a subtype of the delta-opioid receptor we have measured antinociceptive activity of putative delta 1 (DELT I) and delta 2 (DSLET) agonists in weaned and non-weaned 25-day-old rats. In weaned rats, DSLET produced antinociception reversed by the delta 2-antagonist naltriben, but in non-weaned rats DSLET had no effect. Responses to DELT I were evident in both weaned and non-weaned rats and were not antagonised by naltriben.

HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of p107/E2F complexes.

HPV16 is a human tumour virus encoding two principal oncoproteins, E6 and E7. Expression of E7 can induce DNA synthesis in quiescent cells and this property coincides with its ability to bind to the cell proteins pRb and p107. As these cell proteins are regulators of the transcription factor E2F, we have investigated whether the interaction with E7 could result in induction of cell cycle regulated genes.

Memory self-report in Alzheimer's disease and in age-associated memory impairment.

We investigated memory self-report in Alzheimer's disease (AD) and age-associated memory impairment (AAMI). AD and AAMI patients and healthy elderly subjects were administered a self-report memory questionnaire, memory tests, a family-rated memory questionnaire, and a depression scale. The AD group reported worse memory than the control group, but many individual AD subjects reported normal memory.

Estimated prevalence of age-associated memory impairment derived from standardized tests of memory function.

Recent research on the prevalence of age-associated memory impairment (AAMI) has reflected considerable variability, with estimates ranging from 35% to 98%. This variability is attributed to (a) failure to employ the complete diagnostic criteria for AAMI and (b) failure to consider age as a variable in estimating prevalence. Analysis of published normative data on both standard clinical memory tests and computer-simulated everyday memory tests shows a clear increase in the percentage of persons meeting the AAMI memory performance criterion as a function of age.

Accelerated forgetting in Alzheimer-type dementia.

Accelerated forgetting of name-face associations and grocery list items within the first hour postpresentation is demonstrated in 80 persons with Alzheimer's disease (AD) compared to 80 control subjects matched on age, education, and gender. Differences in forgetting which exceeded statistical regression effects remained, even when AD and control subjects were matched on rate of acquisition during the learning trials of name-face associations. Results are discussed in relation to the neuropathology of AD, organic amnestic disorders, and methodological factors concerning previous research on forgetting in persons with AD.

Raven's colored progressive matrices: a normative study of a random sample of healthy adults.

Raven's Colored Progressive Matrices Test (RCPM) was administered to 894 normal healthy adults who were randomly selected in six Italian cities and in the Republic of San Marino. Gender, age, and education significantly influenced overall test performance, and performance on different RCPM subsets. Findings from this large random sample provide demographic corrections to test scores for use in clinical practice.

Learning, forgetting, and retrieval of everyday material across the adult life span.

Levels and rates of acquisition and amounts of forgetting of name-face associations and grocery list items were assessed in a sample of 1,921 normal participants that was divided into five age groups (i.e., 17-39, 40-49, 50-59, 60-69, and 70+).

Biological activities of p53 mutants in Burkitt's lymphoma cells.

Wild-type human p53 and a series of p53 point mutants isolated from Burkitt's lymphoma (BL) cell lines were tested for their ability to inhibit DNA synthesis in a p53-negative BL cell line and to bind and be degraded by the human papillomavirus type 16 E6 protein. All the mutants lost the wild-type ability to inhibit DNA synthesis, demonstrating that they are all functionally altered. Binding to E6 and consequent degradation of the p53 mutants frequently correlated with changed suppressor properties in BL cells.

Human papillomavirus type 16 E7 associates with a histone H1 kinase and with p107 through sequences necessary for transformation.

The transforming function of human papillomavirus type 16 (HPV16) E7 has been shown to depend on activities additional to the ability to bind RB. In this paper we describe two further properties of E7 which may also contribute to transformation, an association with a histone H1 kinase at the G2/M phase of the cell cycle and an ability to bind the RB-related protein p107. The region of E7 identified previously as important for RB binding was found to be involved in the association with the kinase and complex formation with p107, although analysis of E7 point mutants within this region revealed a difference in the precise sequence requirement for RB and p107 binding.