Combination cytotoxic effects of cis-diamminedichloroplatinum(II) and 5-fluorouracil with and without leucovorin against human non-small cell lung cancer cell lines

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.     

Ultrastructural and immunocytochemical features of a case of neuroendocrine carcinoma developing in a prior ileostomy site

A patient who developed a mixed neuroendocrine carcinoma and adenocarcinoma at the site of a previous long-standing ileostomy is reported. The neuroendocrine features are documented by both ultrastructural and immunocytochemical findings. Carcinoma arising in an ileostomy site is rare but has been recorded in patients with long-standing ileostomies after colectomy for chronic inflammatory bowel disease, as in this patient. Neuroendocrine carcinoma developing in this setting apparently has not been described before, however.     

Progressive scoliosis with vertebral rotation after lumbar intervertebral disc herniation in a 10-year-old girl

A case report of a 10-year old girl with a herniated disc is presented. The most significant symptoms were progressive scoliosis with a flat back and paravertebral muscle spasm. An absent H reflex on the left and an increased latency of the somatosensory-evoked potentials of the left posterior tibial nerve were found. The computed tomographic scan of the lumbar spine showed a large central left-sided disc protrusion at the L5-S1 level. Our case presents the youngest patient with documented intervertebral disc herniation and the only one with severe scoliosis and vertebral rotation. The curve was not structural because it improved with surgery and an orthosis was not necessary.     

Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog

An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.     

Hyaluronic acid induced hyaluronic acid binding protein phosphorylation and inositol triphosphate formation in lymphocytes

In this report, the role of 34 kDa HA-binding protein in hyaluronic acid-induced cellular signalling in lymphocytes has been examined. The binding of 125I-HA to lymphocytes in vivo was found to be inhibited by pre-incubation of the cells with anti-34 kDa HA-binding protein antibodies, thus confirming 34 kDa HA-binding protein as the specific HA-receptor in lymphocytes. This observation was substantiated by anti-34 kDa HA-binding protein antibodies immunoblotting and 125I-HA ligand blotting of lymphocytes cell lysate. The HA-induced cell aggregation, tyrosine phosphorylation and cytoskeletal protein phosphorylation demonstrate the HA-induced early cellular signalling events in lymphocytes. Further, to study the involvement of 34 kDa HA-binding protein in mitogen induced lymphocyte signalling, we studied in vivo phosphorylation and secondary messenger formation. The enhanced 34 kDa HA-binding protein phosphorylation by HA and the inhibition of cellular aggregation and IP3 formation by anti-HA-binding protein antibodies revealed that 34 kDa HA-binding protein is one of the potential mediators in HA-induced signal transduction.     

Membranous duodenal stenosis

The experience of our 16 patients treated for membranous duodenal stenosis is reported. Their treatment and course was analysed in a retrospective study. Eight patients were operated on within the first 16 days of life and in the remaining group surgery was performed at 1 month to 4 y of age. The presenting symptom leading to diagnosis was, in all but one case, non-bile-stained vomiting. Associated malformations were found in all but four patients, mostly morbus Down. The operative procedure performed was a partial excision of the duodenal membrane and a duodenoplasty in 10 patients, a duodenojejunostomy in 5 patients, and a duodenoplasty only in 1 patient. The postoperative course was without lethal complications. One late stricture in an anastomosis occurred. We conclude that in its presentation, duodenal stenosis differs from duodenal atresia, and can often be misinterpreted, resulting in a late diagnosis, and should be reported as a separate entity.     

In vivo validation of a thermodilution system designed to measure peripheral blood flow

A 5F triple-lumen thermodilution catheter was evaluated in a canine vena cava model to determine whether this catheter and the thermodilution technique provide valid in vivo determinations of blood flow. Our ultimate goal is to develop methods for studying limb blood flow in humans. Seven dogs were studied. Blood flow was provided and regulated by a calibrated roller pump. Flow rate determinations by thermodilution were made over a range of 0.5 to 5.01 1/minute. Excellent correlation (r = 0.98, r2 = 0.96, P less than 0.01) was found between actual flow and flow measured by thermodilution. The mean (+/- SD) coefficient of variation for the thermodilution method was 9.97 +/- 5.72 per cent over the flow range tested. The coefficient of variation tended to be higher at low flow rates. The thermodilution technique with this catheter provides valid in vivo determinations of blood flow through large vessels. This technology can be rationally applied to the study of limb blood flow in humans.     

Correction factors for water-proofing sleeves in kilovoltage x-ray beams

This paper investigates the effect of the waterproofing sleeve on the calibration of kilovoltage photon beams (50-300 kV). The sleeve effect correction factor, ps has been calculated using the Monte Carlo method as the ratios of the air kerma in an air cavity of a cylindrical chamber without the waterproofing sleeve to that with a sleeve. Three sleeve materials have been studied, PMMA, nylon and polystyrene. The calculations were carried out using the EGS4 (Electron Gamma Shower version 4) code system with the application of a correlated-sampling variance-reduction technique. The results show that the sleeve correction factor for 1-mm thick nylon and polystyrene sleeves, ps varies from 0.992 to 1.000 and from 0.981 to 1.000, respectively, for the same beam quality range. The ps factor varies with sleeve thickness, beam quality and phantom depth. No significant dependence of the ps factor on field size and source-surface distance has been found. Measurements for PMMA, nylon and polystyrene sleeves of various thicknesses have also been carried out and show excellent agreement with Monte Carlo calculations.     

The murine Tcl1 oncogene: embryonic and lymphoid cell expression

In human leukemias and lymphomas nonrandom chromosomal rearrangements cause changes in cell growth and/or survival in such a way as to promote malignancy. The detailed study of the biochemical and genetic pathways altered in human cancer requires the identification or development of models to allow the study and manipulation of cancer gene function. Recently, the breakpoint gene TCL1, involved in chromosome translocations observed mostly in mature T-cell proliferations and chronic lymphocytic leukemias (CLL), was isolated and characterized, and showed to be part of a new gene family of proteins involved in these tumors. The murine Tcl1 gene, is similar in sequence to the murine and human MTCP1 gene also involved in T cell leukemias. The murine Tcl1 gene was shown to reside on mouse chromosome 12 in a region syntenic to human chromosome 14. Furthermore, we show that the murine Tcl1 gene is expressed early in mouse embryonic development and demonstrates expression in fetal hematopoietic organs as well as in immature T and B cells. Characterization of the murine Tcl1 gene will help in developing a mouse model of CLL and would provide the best opportunity to study and decipher the role of TCL1 in malignant transformation.