Very low doses of X-rays can cause human lymphocytes to become less susceptible to ionizing radiation

Cultured human lymphocytes exposed to very low doses of X-raysbecome less susceptible to subsequent higher doses of X-rays.Cells exposed to doses as low as 0.5 rad (cGy) or 1 rad of X-raysat 32–34 h of culture become adapted so that less cytogeneticdamage in the from of chromosome breakage is induced by 150rad administered at 48 h. This response, which does not occurafter high inital doses of X-rays, can be eliminated by 3-aminobenzamide,an inhibitor of poly(ADP-ribose) polymerase.     

Sister chromatid exchange induced by short-lived monoadducts produced by the bifunctional agents mitomycin C and 8-methoxypsoralen

To see if DNA crosslinks are involved in the induction of sister chromatid exchange (SCE), Chinese hamster ovary cells were exposed to two bifunctional alkylating agents, mitomycin C and 8-methoxypsoralen, and their monofunctional derivatives, decarbamoyl mitomycin C and angelicin. The data indicate that monoadducts, rather than crosslinks, are responsible for SCE formation. Furthermore, all agents but angelicin produced short-lived lesions that led to SCEs in the first period of DNA replication after treatment (twin SCEs), but not in the second (single SCEs). In contrast, angelicin, like methyl methanesulfonate and N-acetoxyacetylaminofluorene, produced lesions that lasted more than one cycle, indicating that several different types of DNA lesions are capable of SCE induction.     

Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow

Twenty-seven patients with malignant lymphoma in whom primary chemotherapy had failed and the prognosis was poor were treated with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. The median time to recovery of more than 500 neutrophils per microliter and more than 10,000 platelets per microliter was 18 and 24 days, respectively. Complete remission was achieved in 15 patients (56 per cent), five of whom were in continuous remission at this writing 19 to 71 months after transplantation without further therapy and one of whom was alive in a subsequent remission at 20 months. Fifteen patients died of lymphoma, three of interstitial pneumonitis, two of sepsis, and one of congestive heart failure. This experience shows that intensive therapy and autologous-marrow transplantation can produce prolonged remissions in patients with malignant lymphoma in whom conventional chemotherapy has failed.     

Leucocyte chemotaxis: physiological considerations and abnormalities.

Expression of the inflammatory process is dependent on mobilisation of leucocytes, which require leucocyte chemotaxis. Recent technological advances have enabled extensive in vitro biological characterisation of the chemotatic stimuli (factors) and the cellular events of migration. The chemotatic stimuli include products of complement activation, fibrinolytic and kinin generating systems, collagen products as well as products of bacterial growth and products released from virus-infected tissues. Chemotatic factors are also released as a result of lymphocyte activation and phagocytosis by neutrophils. Other neutrophils products released during phagocytosis activate the complement system. A complex mechanism for limiting production or activity of chemotactic factors has been identified. These antichemotatic agents include serum and cell-derived chemotactic factor inactivators as well as specific inhibitors of leucocyte migration and complement inactivators released from neutrophils during the phagocytic process. The mechanism by which cells respond to chemotatic factors is poorly understood by cell adherence to the substratum, cell deformability, random migration, and directed migration are required. These processes are complex and require modifications of the leucocyte surface, calcium and magnesium, activation of esterases, function of contractile elements and assembly of a cytoskeleton, which is probably modulated by cyclic nucleotide metabolism.     

Chronic periodontal disease is associated with single-nucleotide polymorphisms of the human TLR-4 gene

Periodontitis is an inflammatory disease affecting the connective tissue surrounding the teeth leading to tooth loss. Pathogens associated with periodontitis interact with Toll-like receptors (TLRs) to induce cytokines causing and aggravating disease. We screened 197 individuals suffering from generalized periodontitis for the presence of Asp299Gly and Thr399Ile of TLR-4 as well as Arg753Gln of TLR-2 in comparison to matched controls. Single-nucleotide polymorphisms (SNPs) of TLR-4 were elevated among patients (odd's ratio 3.650, 95% CI 1.573-8.467, P < or = 0.0001), while no difference was observed for TLR-2. TLR-4 SNPs were correlated with chronic periodontitis (odd's ratio 5.562, 95% CI 2.199-14.04, P < or = 0.0001), but not with aggressive periodontitis. This observation was confirmed employing a group of periodontally healthy probands over 60 years of age. These data demonstrate that genetic variants of TLR-4 may act as risk factors for the development of generalized chronic periodontitis in humans.