Loss of heterozygosity for the short arm of chromosome 11 (11p15) in human milk epithelial cells immortalized by microinjection of SV40 DNA.

We have developed, by microinjection of SV40 DNA into human milk epithelial cells, a new mammary cell line, Hu-MI, which exhibits the phenotype of luminal cells or so-called "breast cancer precursor cells." This cell line retains the phenotype of primary cells as demonstrated by the expression of keratins 18 and 19 and of polymorphic epithelial mucins. However, the cells do not grow in agar after more than 80 passages, nor do they form tumors in nude mice. Established cells contain 2 copies of SV40 DNA integrated into the cellular genome and up to 14 copies of free SV40 DNA. A deletion of the short arm of chromosome 11 (11p15) including the c-Ha-ras and the beta-globin genes was found in the immortalized cells when the DNA from these cells was compared to the DNA from peripheral blood mononuclear cells obtained from the same donor. In addition, this cell line showed a good transfection efficiency for other DNA sequences using classical transfection and selection techniques with a neomycin resistance gene (pKOneo). Selective microinjection of DNA into tumor precursor cells may prove useful for the study of the molecular mechanisms involved in breast carcinogenesis. The possible significance of the loss of 11p13-15 in malignant progression of breast cancer is discussed.     

Is verbal recognition memory really different in Huntington's and Alzheimer's disease.

Verbal recall and recognition were examined in Huntington's disease (HD) and Alzheimer's disease (AD) patients. Subgroups of HD and AD patients were matched for overall severity of dementia. Subjects were administered the Hopkins Verbal Learning Test, a list-learning task with three free-recall trials followed immediately by one yes/no recognition trial with semantically related and unrelated distractors. The matched AD and HD groups did not differ in the number of words recalled, although the HD patients showed slightly greater improvement over trials. Recognition performance was evaluated with measures of accuracy and response bias that are independent of each other. The matched groups did not differ in overall recognition accuracy, but the AD patients tended to have a more liberal ("yea-saying") response bias than did the HD patients. In addition, only the AD patients were differentially enticed to false-positive responding by semantically related distractors. The results suggest that the rule for making decisions when uncertain, rather than memory strength per se, distinguishes the recognition memory performance of AD and HD patients.     

Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study

Summary Magnetic resonance imaging and a comprehensive cognitive evaluation were carried out in a series of 29 patients with mild to moderate Huntington's disease (HD). A factor analysis of the neuropsychological test scores provided three factors: a memory/speed-of-processing factor, a frontal factor, and a response inhibition factor. The memory/speed factor correlated significantly with measures of caudate atrophy, frontal atrophy, and atrophy of the left (but not the right) sylvian cistern. There were no significant correlations between the frontal or response inhibition factors and measures of cortical or subcortical brain atrophy. Our findings confirm that subcortical atrophy is significantly correlated with specific cognitive deficits in HD, and demonstrate that cortical atrophy also has important association with the cognitive deficits of patients with HD.     

Quantification of doses to mediastinal lymph nodes in Hodgkin's disease.

Hodgkin's disease is highly curable today. Radiotherapy (RT) is the treatment of choice in the early stages. A mantle field is often used in the RT of Hodgkin's disease, and the technique and dosimetry are quite complex. We used computerized tomography (CT)-based dosimetry to determine doses delivered to different mediastinal nodes with the commonly used technique in Hodgkin's disease that was originally described by Kaplan. We used dose-volume histograms to determine doses to various groups of nodes in nine patients. Significant inhomogeneity (30%, 30%, 35%, 35%, 30%, 40%, 35%, 35%, and 30% in the nine patients) in dose distribution was found within the mediastinum. With the advent of 3-dimensional CT-based treatment planning, we are able to quantify such inhomogeneities. The question arises whether a homogeneous, lesser dose can achieve equal results. Average doses and "effective doses" were also calculated. The "effective doses" in eight patients (for a prescribed dose of 44 Gy) with a midline posterior spinal cord block added at 20 Gy were 37.3 Gy, 34.3 Gy, 36.0 Gy, 38.4 Gy, 35.8 Gy, 38.1 Gy, 36.7 Gy, and 36.7 Gy, respectively. A homogeneous dose equivalent to effective dose may achieve the same control as an inhomogeneous dose delivery. Prospective 3-D dosimetric studies are required to confirm this concept.     

Visuelle Prävention der Bewegungskrankheit im Auto

Zusammenfassung Mit Hilfe von Autoversuchen wurde die früher im Labor für Winkelbeschleunigungen gefundene visuelle Modulation vestibulären Schwindels auf ihre praktische Bedeutung zur physikalischen Prävention von Bewegungskrankheit, vorwiegend durch Linearbeschleunigungen auf der Straße, überprüft.Achtzehn freiwillige Versuchspersonen wurden an drei nicht aufeinanderfolgenden Tagen als Beifahrer in einem Kraftfahrzeug auf einer geraden Autobahn-Teststrecke über 4 × 1,7 km einem festgelegten Muster richtungswechselnder Linearbeschleunigungen (0,1–1,2 g) unter Variation der gleichzeitigen visuellen Reizbedingungen ausgesetzt: I) Augen auf, visuelle Kontrolle der Fahrzeugbeschleunigungen; II) Augen zu; III) Augen auf, künstlicher stationärer Ganzfeldreiz (Kartenlesen).Die Stärke der durch die alternierenden Beschleunigungen ausgelösten Bewegungskrankheit (magnitude estimation 1–10) wurde signifikant durch simultane visuelle Reizbedingungen bestimmt: a) geringe Übelkeit (<1) unter adäquater visueller Bewegungswahrnehmung; b) mittlere Übelkeit (2) bei rein vestibulärer Reizung und geschlossenen Augen; c) starke Übelkeit (>5), wenn die visuelle Information scheinbarer Unbewegtheit den labyrinthären Beschleunigungsreizen widerspricht. Bewegungskrankheit in Autos entsteht vorwiegend durch visuell-vestibuläre Reizkonflikte und läßt sich wirkungsvoll durch visuelle Kontrolle der auftretenden Fahrzeugbeschleunigungen unterdrücken.Mit Unterstützung der Deutschen Forschungsgemeinschaft Br639/3 Bewegungskrankheit und der DFVLR Biomedizinische Untersuchungen des Experiments Space-Sled     

The effect of bacterially produced vitamin B12 analogues (cobamides) on the in vitro absorption of cyanocabalamin.

An incubation system containing rat jejunoileum was used to determine whether analogues of cyanocabalamin (CNCbl) inhibited the in vitro absorption of CNCbl. The naturally occurring analogues "pseudo B12," "factor A," and the nonnaturally occurring analogue desdemethyl B12, were produced by guided biosynthesis with Propionibacterium arabinosum. Factor B was produced by acid cleavage of cyanocabalamin. Inhibition of Co57-CNBbl uptake was demonstrated for cold CNCbl and for desdemethyl B12, although statistical significance was achieved only for cold CNCbl at 40X and 100X the molar quantity of the radiolabeled CNCbl. However, a trend towards progressive inhibition of specific CNCbl binding was shown as increasing concentrations of CNCbl or desdemethyl B12 were used. No inhibition of specific CNCbl binding could be demonstrated for any of the naturally occurring cobamides tested.     

Posttraumatic stress two years after the Oklahoma City bombing in youths geographically distant from the explosion

This article describes Posttraumatic Stress Disorder (PTSD) symptomatology in 69 sixth-grade youths who resided within 100 miles of Oklahoma City at the time of the 1995 bombing of the Alfred P. Murrah Federal Building. These youths neither had any direct physical exposure nor personally knew anyone killed or injured in the explosion. A survey conducted two years after the bombing assessed exposure, PTSD symptoms, and functioning. PTSD symptom frequency was measured with the Impact of Event Scale--Revised. Our BCD criteria for defining PTSD caseness was modeled after DSM-IV B, C, and D criteria requiring one reexperiencing, three avoidance/numbing, and two arousal symptoms for diagnosis. Those who met our BCD criteria had significantly higher PTSD symptom scores than those who did not. Both increased mean PTSD symptom score and meeting our caseness definition were associated with increased functioning difficulties. Media exposure and indirect interpersonal exposure (having a friend who knew someone killed or injured) were significant predictors of symptomatology. These findings suggest that children geographically distant from disaster who have not directly experienced an interpersonal loss report PTSD symptoms and functional impairment associated with increased media exposure and indirect loss.     

Vom Antigen zum Tumormarker Forschungsergebnisse zu PSA und ihre klinische Umsetzung

The determination of prostate-specific antigen is credited with dramatic advances in the early detection of men with prostatic carcinoma. This report summarizes the history of biochemical research and current status of prostate-specific antigen in tumor diagnostics.     

Use of artificial neural networks in evaluating prognostic factors determining the response to dendritic cells pulsed with PSMA peptides in prostate cancer patients

BACKGROUND: Our purpose was to compare the importance of over 22 measurements used in evaluating the clinical responses of patients with metastatic or locally recurrent prostate cancer, treated by dendritic cell (DC) infusions with prostate-specific membrane antigen (PSMA) peptides. METHODS: Artificial neural networks (ANNs) were employed for assessment, as well as the traditional methods of logistic regression. RESULTS: Twenty-six patients with metastatic disease and 37 patients with local recurrence were available for evaluation and comparison. ANN evaluation ranked the collective effects of DC infusion, immune responses (CD3+ cells, CD16+ cells, zeta chain+ cells), and cytokines, e.g., IL-6 and PSMA levels, very highly. Logistic regression identified all of these parameters to some degree, but in a different rank order. Patients with metastases showed a sharp rate of response secondary to the level of DC infusion, in contrast to those patients with local recurrence, in which it was more gradual. CONCLUSIONS: ANN analysis emphasizes the importance of level of DC infusion, immune parameters, cytokines, and markers such as PSMA in determining the response to PSMA peptide immunotherapy. The criteria of response were judged to be correct in 86% of metastatic patients and 83% of locally recurrent patients evaluated in this study.     

Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies.

Intervention trials with supplemental beta-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7-16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. beta-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87-1.11; highest versus lowest quintile). The RRs for alpha-carotene, lutein/zeaxanthin, and lycopene were also close to unity. beta-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67-0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in beta-cryptoxanthin, such as citrus fruit, may modestly lower the risk.