Use of stem cells from mismatched related donors

Mismatched haploidentical bone marrow transplantations from a related donor have been the topic of clinical and laboratory research for more than 20 years. During that time, new treatment strategies have been designed based on animal experiments, and, since our group introduced the megadose inoculum which combines T-cell-depleted bone marrow cells with a large number of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells and a more intensive conditioning regimen, have done much to overcome the problems of graft-versus-host disease and graft rejection. As most patients have a full haplotype mismatched relative available, this technique means that a far greater number of patients with hematologic malignancies can be offered a T-cell-depleted transplantation as curative therapy.     

Nitric oxide synergistically enhances DNA strand breakage induced by polyhydroxyaromatic compounds, but inhibits that induced by the Fenton reaction

This paper deals with the muscle force of the cervical spine in patients with cervical syndrome compared to the muscle activity in non-patients. It has thus been observed that both the flexors' and the extensors' force of the cervical spine is much greater in non-patients (the flexors' P < 0.01 and the extensors' P < 0.01). The precise measurements having been carried out by a dynamometer. The groups being tested comprised 50 persons each, 25 men and 25 women. The average age of the patients group was 43.1 years, namely between 21 and 57 years, while that of the non-patients group was 42.3 years, between 24 and 56 years. As regards the professional engagement of both groups and, accordingly, the strain on the cervical spine and the corresponding musculature, they were approximately the same.     

New fault locating system for air-insulated substations usingoptical current detector

The authors present the basic philosophy, construction, design features, and test results of a new fault locating system. This fault locating system helps to shorten the time required for restoration of service after the occurrence of a busbar fault in an air-insulated distribution substation. Recent optical and electronic technologies allow the design of a highly accurate and compact fault locating system which consists of optical current detectors using the Faraday effect and a fault locating processor using a digital data processing technique. The fault location is carried out by discriminating between the directions of zero-sequence currents. Through various tests and field operations, it has been confirmed that the system has sufficient performance for practical applications     

Pulmonary vascular disease and operative indications in complete atrioventricular canal defect in early infancy

Pulmonary vascular disease was morphometrically analyzed in 67 patients (mean age, 19 months) with isolated complete atrioventricular canal defect. Complete obstruction of the small pulmonary arterial lumen resulting from acute fibrous proliferation and atrophy of the peripheral arterial media, which were considered absolute operative contraindications, were characteristic in six patients with Down's syndrome. Morphometric analysis of medial thickness revealed that thinning of the media of the small pulmonary arteries is generally observed at around 6 months of age in patients with complete atrioventricular canal defect and that the media in patients who have complete atrioventricular canal defect and Down's syndrome was thinner than that in such patients without Down's syndrome. These results suggest that thinning of the media as a result of two factors--Down's syndrome and aging--facilitates the rapid occurrence of fibrous intimal proliferation. Therefore intracardiac repair is desirable within 6 months of life, before medial thinning, in patients with complete atrioventricular canal defect and Down's syndrome. Excluding patients with absolute operative contraindications, the scores of the index of pulmonary vascular disease in operative survivors were below 2.0 and death occurred when scores were more than 2.2. The pulmonary vascular resistances measured in room air and by the oxygen inhalation and tolazoline tests in patients with operative contraindications were more than 7.3, 3.8, and 6.6 units.m2, respectively. We thus conclude that lung biopsy should be undertaken for patients in whom pulmonary vascular resistance is beyond these values to determine the appropriateness of surgical intervention.     

Competitive inhibition by procaine of carbachol-induced stimulus-secretion coupling in rat pancreatic acini

1. Procaine (0.03-10 mM) inhibited carbachol (CCh)-induced amylase release from rat isolated pancreatic acini in a competitive manner. Kinetic analysis of the relation between CCh concentrations and the amount of amylase released in the presence of various procaine concentrations indicated that procaine caused competitive inhibition with the affinity constant (pA2) value of 5.00 +/- 0.08. 2. Receptor binding assay confirmed that procaine (0.01-10 mM) competitively inhibited [N-methyl-3H]-scopolamine chloride ([3H]-NMS) binding to its receptor with binding affinity (pKi) of 4.63 +/- 0.10. 3. Procaine transformed CCh-evoked [Ca2+]i dynamics: the initial rise in [Ca2+]i followed by a gradual decay during continuous stimulation with 3 microM CCh was transformed by 0.3 mM procaine to the oscillatory [Ca2+]i dynamics, which resembled the response to 0.3 microM CCh in the absence of procaine. The initial phase of [Ca2+]i oscillation corresponded to the initial phase of CCh-induced amylase release in isolated perfused acini. 4. Procaine (0.3-3 mM) did not inhibit the secretory response to cholecystokinin octapeptide (CCK-8) in isolated incubated acini. A higher concentration of procaine (10 mM) caused weak but significant inhibition of the response to only limited concentrations of CCK-8, 30 and 100 pM. Procaine lower than 10 mM was ineffective on [125I]-BH-CCK-8 binding, although procaine (10 mM) caused weak but significant inhibition of the binding.     

Overgrowth and DNA synthesis of neuroepithelium in embryonic stages of induced Long-Evans rat myeloschisis

Overgrowth of the myeloschisis, namely the excessive amount of the neural plate tissue, has been reported in the human myeloschisis. However, it is still debatable how the overgrowth develops and whether the overgrowth is the cause, or the secondary effect of spinal dysraphism. The author induced myeloschisis in the fetuses of Long-Evans rats by the administration of ethylenethiourea (ETU) to pregnant rats on day 10 of gestation. The fetuses were removed 1 hour after the treatment with bromodeoxyuridine (BrdU) to the dams on day 14 and 21. The fetuses were fixed in alcohol and embedded in paraffin. H-E staining and the immunohistologic examination were performed on the staining patterns to anti-neurofilament (NFP), anti-glial fibrillary acidic protein (GFAP) and anti-BrdU antibody by ABC method. On day 14, the lateral portion of everted neural plate showed a loose arrangement of cells and there was rosette formation in the mesoderm. On day 21, cell necrosis was observed at the dorsolateral portion of myeloschisis, although the ventral portion showed almost normal cytoarchitecture and was positive to NFP and GFAP. The cause of myeloschisis in this model is supposed to be the local and direct cytotoxic effect of ETU to neuro-ectodermal junction. On day 14, control animals contained few BrdU-incorporated cells at the basal plate of neural tube. In contrast, everted neural plate showed an active uptake of BrdU diffusely in the subependymal matrix layer cells. Overgrowth was not yet identified. On day 21, overgrowth of myeloschisis was found in spite of a few positive cells to BrdU which was identical to the control animals. These findings seem to suggest that cells in the myeloschisis retain their ability of DNA synthesis for longer periods of development and overgrowth found on day 21 is possibly a secondary effect of spinal dysraphism in this model.     

A rapid dot-blot method for species identification of bloodstains

A very simple and rapid test for species identification is reported. Extracts of bloodstains were applied to a synthetic porous membrane and dried. The membrane was then quenched with glycine buffered saline containing BSA and Tween 20. A suspension of colloidal gold particles (GP) coated with rabbit antiserum to human IgG was poured onto, gently whirled and aspirated through the membrane. Spots from the human and monkey bloodstains became red, whereas those from other species of animals remained unstained. This test was completed within 3 to 4 min, and the antibody-coated GP reagent was prepared within 20 min using a very small quantity of antiserum. Cellulose acetate membranes of 0.45 microns or more in pore size were appropriate to this test.     

Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2

Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.