Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures

Background  

Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment.     

Cause of kinematic differences during centrifugal and centripetal saccades

Measurements of eye movements have shown that centrifugal movements (i.e. away from the primary position) have a lower maximum velocity and a longer duration than centripetal movements (i.e. toward the primary position) of the same size. In 1988 Pelisson proposed that these kinematic differences might be caused by differences in the neural command signals, oculomotor mechanics or a combination of the two. By using the result of muscle force measurements that were made in recent years (Orbit 1.8 Gaze mechanics simulation, Eidactics, San Francisco, 1999) we simulated the muscle forces during centrifugal and centripetal saccades. Based on these simulations we show that the cause of the kinematic differences between the centrifugal and centripetal saccades is the non-linear force-velocity relationship (i.e. muscle viscosity) of the muscles.     

Bone marrow precursor of extranodal T-cell lymphoma

The development of extranodal lymphomas is thought to be initiated by the transformation event in peripheral organs. Lymphomatoid papulosis (LyP) is a low-grade cutaneous lymphoma and may progress into the cutaneous anaplastic lymphoma. We identified 2 patients who 3 and 4 years before the development of LyP were treated for an unrelated malignancy (Burkitt lymphoma and small-cell B-cell lymphoma). We analyzed the T-cell receptor (TCR) gene rearrangement pattern in their skin, blood, and bone marrow, including the archival bone marrow sampled years before the development of clinically evident LyP. In all samples we detected the unique monoclonal TCR rearrangements. This observation suggests that the initial malignant transformation in LyP occurred in bone marrow and not, as could be supposed, in the skin.     

Radio-frequency tumor ablation: internally cooled electrode versus saline-enhanced technique in an aggressive rabbit tumor model

PURPOSE: To compare two methods of radio-frequency (RF) ablation, saline enhancement technique and internally cooled electrodes, for the treatment of small breast cancers in an animal model--highly aggressive VX2 rabbit tumors surrounded by adipose tissue. MATERIALS AND METHODS: Twenty-seven tumors were implanted into retroperitoneal fat of 14 New Zealand White rabbits. RF ablation was performed with ultrasonographic (US) guidance after tumors had grown to 15 mm. Fourteen tumors in seven animals were treated with internally cooled electrodes (30-mm-tip single electrode, 60 W, 10 min); 13 tumors in seven animals, with saline enhancement (0.5 mL/min of saline, 25-mm tip, 30 W, 10 min). Autopsy and histopathologic assessment were performed 3 weeks after therapy. RESULTS: Real-time US of RF ablation was not possible with either method because of obscuration by the increasing hyperechogenicity of the tumor and the surrounding adipose tissue. Equivalent efficacy was demonstrated with the two methods. Significantly greater complications were observed with the saline technique: Free retroperitoneal fluid was detected in one of seven animals with internally cooled electrodes and in all seven animals with saline enhancement (P <.01). Damage to remote structures such as the kidney, spine muscle, and skin was observed at autopsy in one of seven animals with internally cooled technique versus five of seven with saline enhancement (P <.01). CONCLUSION: Given a lower complication rate and similar treatment efficacy in an animal tumor model, internally cooled RF electrode may be advantageous to adjuvant saline infusion for the minimally invasive treatment of breast tumors.     

Die psychomotorische Epilepsie im Kindesalter

Ohne Zusammenfassung     

Cerebello-oculo-cutane Teleangiektasien (Louis-Barsche Krankheit)

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Anti-oxidant vitamins reduce normal tissue toxicity induced by radio-immunotherapy

Our purpose was to determine whether the administration of anti-oxidant vitamins could reduce dose-limiting toxicity from radio-immunotherapy (RAIT) and thereby allow higher escalation of RAIT doses. Lipophilic vitamins A and E were administered i.p. and hydrophilic vitamin C was administered i.m. for 14 days (3 days pre-RAIT through 11 days post-RAIT) alone or with bone marrow transplantation (BMT) to either BALB/c mice for toxicity studies or to nude mice bearing s.c. GW-39 human colonic cancer xenografts for therapy studies. The maximal tolerated dose (MTD) of RAIT ((131)I-MN14 anti-CEA IgG) that results in no lethality was determined for mice that did not receive vitamins or BMT and those that did receive one or both interventions. Body weight, peripheral white blood cell (pWBC) and platelet (PLT) counts and tumor growth were also measured. Administration of vitamins (equivalent of 3.5 IU/day vitamin A, 0.107 IU/day vitamin E and 4.0 mg/day ascorbic acid) to mice along with BMT increased the MTD by 42% and reduced body weight loss associated with RAIT. Vitamins also reduced the magnitude of RAIT-induced myelosuppression. As early as day 7 after RAIT, vitamins increased WBC counts following both a 400 microCi and a 500 microCi dose. On day 14 after the 400 microCi dose of RAIT (day 7 post-BMT), the additive effect of BMT and vitamin could be detected. Tumor growth was not adversely affected by vitamin administration.     

Origin of macrophages in traumatic lesions and Wallerian degeneration in peripheral nerves

Summary The origin of the macrophages in peripheral nerves was investigated in newborn rabbits after labelling the blood monocytes with intravenous carbon suspensions.Carbon labelled lipid macrophages were observed at the site of trauma in the nerves but not in areas of Wallerian degeneration. It is suggested that in Wallerian degeneration, resorption of degenerate tissue is performed by endogenous cells only, while in traumatic lesions part of the phagocytosis is performed by migrated monocytes. The early increase in vascular permeability in traumatic lesions may be a prerequisite for the attraction of the monocytes.     

Evidence for glutamatergic neuronal dysfunction in the prefrontal cortex in chronic but not in first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study

Based upon pharmacological challenge and postmortem studies, schizophrenia has been hypothesized to be caused by decreased glutamatergic neurotransmission. We investigated the glutamatergic neuronal metabolism of the dorsolateral prefrontal cortex with localized 1H magnetic resonance spectroscopy in 18 first-episode patients, 21 chronic patients with schizophrenia, and 21 age-matched controls. Chronic patients had significantly lower levels of glutamate/glutamine (Glx) and N-acetylaspartate (NAA) compared to healthy controls and first-episode patients. Reduced metabolite levels were not correlated with duration of illness or medication. Our results indicate glutamatergic dysfunction in chronic schizophrenia that could be evidence of a progressive brain disorder.