Angiostatin overexpression in Morris hepatoma results in decreased tumor growth but increased perfusion and vascularization.

Growth of malignant tumors is dependent on sufficient blood supply. Thus, inhibition of tumor angiogenesis is emerging as a promising target in the treatment of malignancies. Human angiostatin (hANG) is one of the most potent inhibitors of endothelial cell proliferation, angiogenesis, and tumor growth in vivo. However, its mechanisms operating in vivo are not well understood. METHODS: To obtain more information about functional changes in the angiogenic process, we established Morris hepatoma (MH3924A) cell lines expressing hANG (hANG-MH3924A). The effects of hANG expression on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) were measured in coculture experiments in vitro. To evaluate changes in tumor perfusion and blood volume, H2 15O and 68Ga-DOTA-albumin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) were used for PET studies in vivo. Additionally, immunohistologic quantification of vascularization, apoptosis, and proliferation as well as gene array analyses were performed. RESULTS: Our in vitro experiments demonstrate reduced proliferation and increased apoptosis in HUVECs when being cocultured with hANG-MH3924A. In support, tumor growth of hANG-MH3924A is diminished by 95% in vivo. However, tumor perfusion and blood volume are increased in hANG-MH3924A corresponding to an increased microvessel density. Furthermore, hANG-transfected tumors show changes in expression of genes related to apoptosis, stress, signal transduction, and metabolism. CONCLUSION: hANG expression leads to inhibition of tumor growth, increased apoptosis, and changes in the expression of multiple genes involved in stress reactions, signal transduction, and apoptosis, which indicates a multifactorial reaction of tumors. An enhanced microvessel density is seen as part of these reactions and is associated with increased perfusion as measured by PET.     

Schedule-induced cocaine drinking: choice between cocaine and vehicle

Rats were exposed to daily 3-hr schedule-induced polydipsia sessions (fixed-time 1-min food-pellet delivery) with two drinking fluids available: cocaine solution and water. Fluid position was alternated daily. Polydipsia occurred mostly from a preferred-side spout (position preference) until cocaine solution concentration was increased to between 0.52 and 1.04 mg/ml and animals drank mostly water. Within a lower concentration range (0.28-0.6 mg/ml) maximum session cocaine intakes ranged from 54.3 to 120.1 mg/kg. Postsession serum cocaine levels were about 200 ng/ml. At individually chosen cocaine solution concentrations, the addition of saccharin to the solution did not increase cocaine intake, but a compound solution (saccharin plus glucose) did. With progressive dilution of the compound vehicle, an almost complete preference for cocaine solution was maintained. But with a return to water as the vehicle, animals reverted to a position preference after a few sessions, although one maintained a clear cocaine preference. Schedule-induced polydipsia produced chronic, oral self-administration of cocaine resulting in pharmacologically significant intakes and serum levels.     

Brain tissue microarrays in dementia research: White matter microvascular pathology in Alzheimer's disease

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non‐neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well‐characterized materials (e.g. in quantitative mapping of white matter changes).     

A treadmill test of sprint running

Anaerobic power is characterized by a high degree of specificity regarding both the recruited muscles as well as the recruitment pattern. The popular Wingate Anaerobic Test (WAnT) is a cycling test that does not satisfy the need for a running-specific anaerobic test. We describe such a test, using a novel type of a commercially available treadmill (BRL 1800, Gymrol, France). The ergometer is equipped with a torque motor to neutralize the frictional resistance of the treadmill belt, and a hip-belt harness connected to a horizontal rod. Force applied to the harness is monitored by a strain gauge mounted on the rod, while vertical movement is monitored by a potentiometer at the posterior fixed end of the rod. These, in conjunction with the treadmill belt speed, enable the computation of horizontal and vertical power as well as the combined total output. Power is calculated both as 'peak' power (highest 2.5 s segment) and 'mean' power (20 s duration). Preliminary results of young athletes were generally consistent with the expected age-related changes in anaerobic power. Values obtained on the anaerobic treadmill were always higher than the corresponding WAnT values previously obtained in comparable age groups. The higher values were probably due to the larger muscle mass involved and the shorter peak and mean power durations (2.5 and 20 s versus 5 and 30 s in the WAnT, respectively). This test should enable not only running-specific anaerobic power monitoring but also the characterization of the relationship between the horizontal and vertical components of that power.     

The effect of major railway accidents on the psychological health of train drivers—I. Acute psychological responses to accident

The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8).

Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person.     

Thoraskopische Koronarchirurgie

Thorascopic coronary surgery has achieved great progress in the past few years. After computer-directed instrument systems were introduced, which enabled high precision and expanded mobility in close quarters, the limitations of conventional endoscopic instruments were largely overcome. Employing modern surgical telemanipulators and endoscopic stabilizers, entirely endoscopic myocardial revascularization of the anterior wall is being successfully performed during off-pump surgery. Longer operating times and conversion rates in about one-fifth of the patients due to technical and anatomical limitations still restrict the use of these new surgical techniques compared to conventional surgery. Development of further technologies and integration of video-assisted navigation systems will broaden the application of computer-assisted instrument systems in the near future.