Ventilation and perfusion imaging by electrical impedance tomography: a comparison with radionuclide scanning

Cytokine gene transfer into tumor cells has been shown to mediate tumor regression and antimetastatic effects in several animal models via immunomodulation. Therefore, clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumor cells. We inserted the genes coding for the p35 and p40 chain of interleukin-12 (IL-12) in two independent eukaryotic expression vectors and transduced melanoma cells of 15 different primary tumor cultures with both plasmids by a ballistic gene transfer approach. Secreted IL-12 demonstrated strong bioactivity by inducing interferon-gamma release from peripheral blood lymphocytes upon coculture with cell culture supernatants after IL-12 gene transfer which could at least partly be blocked by IL-12-specific antisera. Further enrichment of transduced tumor cells by magnetic separation directly after gene transfer increased cytokine secretion from a mean of 119 pg in the unsorted to 507 pg IL-12 (24 h/10(8) cells) in the magnetically enriched cell fraction. Irradiation of these cells led to a further elevation of secreted IL-12 (mean 987 pg). Elevated IL-12 levels were detected over 7 days after irradiation in vitro. In a subsequent first clinical phase I study six patients with metastatic melanoma were vaccinated with autologous, interleukin-12 gene-modified tumor cells. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by ballistic gene transfer, irradiated and were then injected subcutaneously (s.c.) at weekly intervals. Clinically, there was no major toxicity except for mild fever. All patients completed more than four s.c. vaccinations over 6 weeks and were eligible for immunological evaluation. Post-vaccination, peripheral mononuclear cells were found to contain an increased number of tumor-reactive proliferative as well as cytolytic cells as determined by a limiting dilution analysis in two patients. Two patients developed DTH reactivity against autologous melanoma cells and one had a minor clinical response. Biopsies taken from that patient's metastases revealed a heavy infiltration of CD4+ and CD8+ T lymphocytes. In conclusion, vaccination induced immunological changes even in a group of advanced, terminally ill patients. These changes can be interpreted as an increased antitumor immune response.     

Human coenurosis in North America: case reports and review

To validate the use of mood induction with older adults, 22 older participants receiving a depressed mood induction were compared with 20 controls and 17 older persons with high Center for Epidemiologic Studies-Depression Scale (CES-D) scores. The mood induction procedure, using self-referent statements and music, changed Depressive Adjective Checklist and CES-D scores in each of 2 sessions 1 week apart. Findings indicated that the use of mood induction procedures with older adults can provide experimental control of mood.     

The papillomavirus minor capsid protein, L2, induces localization of the major capsid protein, L1, and the viral transcription/replication protein, E2, to PML oncogenic domains

Periodontitis and atherosclerosis have complex etiologies, genetic and gender predispositions, and potentially share many risk factors-the most significant of which may be smoking status. These diseases also have many pathogenic mechanisms in common. It is becoming increasingly clear that infections and chronic inflammatory conditions such as periodontitis may influence the atherosclerotic process. The severity and chronicity of periodontal disease provides a rich source of subgingival microbial and host response products and effects over a long time period. The objective of this review is to consider the mechanisms whereby diseases such as periodontitis, which is chronic and Inflammatory In nature and initiated by microbial plaque, can predispose to atherosclerosis. In common with periodontal disease. the pathogenesis of atherosclerosis is not completely understood and both diseases are currently under Intensive investigation. Two main processes in particular are worthy of consideration and may provide the link between these 2 diseases, namely the lipopolysaccharide-related responses and the hyperresponsive monocyte phenomenon. Insufficient experimental evidence exists, however, to further support these hypotheses at present and clearly more research is needed on both of these processes and the interrelationships between both diseases.     

Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies

Rats exposed to trichloroethylene, either by gavage or by inhalation, excreted large amounts of formic acid in urine which was accompanied by a change in urinary pH, increased excretion of ammonia, and slight increases in the excretion of calcium. Following a single 6-h exposure to 500 ppm trichloroethylene, the excretion of formic acid was comparable to that seen after a 500 mg/kg dose of formic acid itself, yet the half-life was markedly different. Formate excretion in trichloroethylene treated rats reached a maximum on day 2 and had a half-life of 4-5 days, whereas urinary excretion was complete within 24 h following a single dose of formic acid itself. Formic acid was shown not to be a metabolite of trichloroethylene. When rats were exposed to 250 or 500 ppm trichloroethylene, 6 h/day, for 28 days, the only significant effects were increased formic acid and ammonia excretion, and a change in urinary pH. There was no evidence of morphological liver or kidney damage. Long-term exposure to formic acid is known to cause kidney damage suggesting that excretion of this acid may contribute to the kidney damage seen in the long-term studies with trichloroethylene.     

The role of staging laparoscopy for multimodal therapy of gastrointestinal cancer

BACKGROUND: This prospective study was conducted to evaluate the accuracy and the therapeutic relevance of staging laparoscopy. METHODS: Between June 1993 and February 1997 staging laparoscopy was performed in 389 patients with various neoplasms. Additionally, 144 selected patients of this group were examined with laparoscopic ultrasound using a semiflexible ultrasound probe (7.5 MHz). RESULTS: Compared to conventional imaging methods, laparoscopy and laparoscopic ultrasound improved the accuracy of staging in 158 of 389 patients (41%). Statistical subgroup analysis of 131 patients with gastric cancer showed that the accuracy of staging laparoscopy in the detection of distant metastases (68%) was significantly higher (p < 0.01) than that of ultrasound (63%) or computed tomography (58%). In the whole group, laparoscopy alone disclosed intraabdominal tumor dissemination or nonresectable disease in 111 patients. Laparoscopic ultrasound displayed additional metastases-i. e., liver metastases (n = 9), M1 lymph nodes (n = 15), or nonresectable tumors (n = 6) in 30 patients. Although metastastic disease was suggested by preoperative imaging, benign lesions were found in five patients with laparoscopy and in a further 12 patients with ultrasonography. The findings of staging laparoscopy changed the treatment strategy in 45% of the patients. Conversion to open surgery was necessary in 5% of the cases, and complications related to laparoscopy occured in 4% of the patients. CONCLUSIONS: Laparoscopy with laparoscopic ultrasound improves the staging of gastrointestinal tumors and has a significant impact on a stage-adapted surgical therapy.     

Specific detection and quantification of palmitoyl-stearoyl-phosphatidylserine in human blood using normal-phase liquid chromatography coupled with electrospray mass spectrometry

We have made an immunohistochemical study of the vomeronasal (VN) complex of 12-day-old rats to characterize the innervation of its blood vessels. The VN complex can be subdivided into rostral, middle and caudal segments, each one with a particular vascularization pattern. Several small vessels were associated with the rostral segment, whereas a large venous sinus ran along the middle and caudal segments. Immunostaining for alpha-smooth muscle actin demonstrated that the muscular sheath was asymmetric, with more cells layers in its lateral than in its medial walls. Nerves were demonstrated with antisera against protein gene product 9.5 (PGP), and against several molecules associated with specific classes of nerve fibers: the C-terminal peptide of neuropeptide Y (CPON), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (NOS). The latter, was also studied with NADPH-diaphorase. Vascular associated fibers exhibited NOS-, CPON-, GAL-, CGRP-, SP- and VIP-immunoreactivity. Only the vessels of the rostral segment showed VIP-immunoreactive fibers. Each wall of the venous sinus exhibited different types of nerve fibers. CPON-, GAL-, CGRP- and SP-immunoreactive fibers concentrated in the medial wall, whereas NOS-immunoreactive ones concentrated in the lateral wall. This distribution of vascular fibers, plus the presence of sensory fibers exhibiting CGRP-, SP- and GAL-immunoreactivity within the pseudostratified epithelium of the VN tube, would be relevant to understand the operation of the pumping mechanism regulating influx and efflux from the VN tube.     

Effects of adenosine, ATP, and UTP on chloride secretion by epithelia explanted from fetal rat lung

To determine the role of intensive chemotherapy and allogeneic bone marrow transplantation (BMT) in treatment of refractory anemia with excess of blasts (RAEB) or RAEB-t (in transformation), the outcome of 37 consecutive children, 12 with RAEB and 25 with RAEB-t, diagnosed between 1985 and 1995 was analyzed. Fourteen patients received intensive chemotherapy according to the AML-BFM protocols 83, 87, or 93 (group 1). Seven patients were treated less intensively with the 6-week consolidation phase as induction (group 2). Allogeneic BMT was performed in 10 children of group 1 and 2 after, and in eight (group 3) without prior chemotherapy. Eight children received minimal or no chemotherapy (group 4). Of 21 children (groups 1 and 2) 17 (81%) achieved complete or partial remission after chemotherapy, 12 of them (10 of group 1) remained in remission, eight after BMT. Five-year survival in 29 children treated intensively (groups 1-3) was 46%, SE 12%. Two of the other eight children (group 4) remained alive, one after spontaneous remission. Outcome after BMT was related to the blast count in the bone marrow prior to BMT. None of 10 children (including two with minimal or no chemotherapy) with < or = 12% blasts before BMT relapsed, in contrast to five of eight patients with a higher blast count (P log rank 0.02). We conclude that a substantial number of children with RAEB or RAEB-t can achieve remission with intensive AML-specific chemotherapy. In patients responding to intensive chemotherapy an increase in long-term survival after allogeneic BMT can be expected.