HPA-alloimmunization is a major factor in refractoriness to HLA-matched platelet transfusion. Retrospective studies indicate that although HPA-matched platelet transfusion is effective in such cases, ...it is extremely difficult to deal with such situations prospectively. We report a case of successful transfusion of HPA-matched platelets selected by HPA-DNA typing with frozen lymphocytes of HLA-matched donors. The patient was a 51-year-old male with CML who developed HLA antibodies after multiple trnasfusion of random platelets. However, HLA-matched platelets were ineffective. Further serological tests including monoclonal antibody-specific immobilization of platelet antigens (MAIPA) revealed that he also possessed HPA-3a antibody, which appeared to be responsible for the refractoriness. HPA-DNA typing by the PCR-SSP method indicated that his HPA-3 type was b/b and those of refractory donors were HPA-3a/a or HPA-3a/b. By HPA-3 typing with 122 frozen lymphocytes of HLA-matched donors, 14 donors were found to be HPA-3b/b. HLA-HPA matched platelets from these donors were shown to be effective, indicating that refractoriness in this patient was due to HPA-3a-alloimmunization. The method described here for selection of HLA-HPA matched donors is effective under the following circumstances: 1) a considerable number of HLA-matched donors and their frozen lymphocytes are available; 2) HPA matching frequency of a given case is not rare; and 3) transfusion of matched platelets is expected to be terminated in a limited period.
Preventive effects of whey mineral concentrate which contained most of the milk minerals and low molecular weight whey protein on the development of hypertension in spontaneously hypertensive rats ...(SHR) were investigated. SHR after weaning were fed the experimental regimen (whey mineral diet or control diet) and maintained on these diets for approx. 10 weeks. A significant inhibition of development of hypertension was observed in the 4th week with male SHR fed the whey mineral diet compared with sex-matched SHR fed the control diet supplemented with a NaCl equivalent. The decrease in blood pressure became more pronounced as the period proceeded. The average blood pressure in male SHR at the end of the experiment was 213mmHg (whey mineral group) and 236mmHg in the control group. A similar result was obtained with female SHR. Accompanying attenuation of blood pressure, urinary excretion of Na and retention of Ca were enhanced by ingestion of the whey mineral concentrate. Blood pressure correlated inversely with urinary Na excretion (r=-0.62), and positively with urinary Ca excretion (r=0.78). Which factor in whey mineral concentrate mainly contributes to these effects, remains unclarified.
Aggregation and secretion of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP) were greatly reduced by the development of the hypertension compared with those of platelets ...from agematched normotensive Wistar-Kyoto rats (WKY). Concomitantly, thrombin-induced phosphorylation of the 47 kDa protein in SHRSP platelets was significantly decreased. However, TPA-induced aggregation, secretion and 47 kDa protein phosphorylation in SHRSP platelets were similar to those in WKY platelets. These results suggest that protein kinase C activity and its substrate were normally present in SHRSP platelets and that defects in the receptor-mediated activation of protein kinase C. This defective protein phosphorylation may be an underlying mechanism for the dysfunction of SHRSP platelets.
We have previously reported that intratracheal instillation of diesel exhaust particles (DEP) to rats caused an increase of protein concentration in broncho-alveolar lavaged fluid (BALF) and ...migration of neutrophils. In addition, alveolar cells from intratracheally DEP-instilled rats expressed inducible NO synthase (iNOS) mRNA and formed peroxynitrite at resting and TPA (12-O-tetradecanoylphorbol 13-acetate)-stimulated states. To clarify the underlying mechanisms for pathophysiological effects of DEP on the lung, the mechanism of the formation of peroxynitrite which plays an important role in pulmonary inflammation, was investigated in this study. DEP (1 mg/kg) was intratracheally instilled to Sprague Dawly rats and alveolar cells were collected from BALF 24 hours after the instillation. Macrophages and neutrophils in BALF were separated from each other by Percoll density gradient centrifugation. Peroxynitrite formation was analyzed using luminol-mediated chemi-luminescence by Luminoskan (Labsystems). Alveolar neutrophils released a much greater amount of peroxynitrite on TPA-stimulation than macrophages. At resting, neutrophils and macrophages produced a less amount of peroxynitrite. These results suggested that migrated neutrophils in airway by DEP-instillation are a main source of peroxynitrite and play a critical role in DEP-caused pulmonary inflammation. Expression of iNOS mRNA by RT-PCR in migrated neutrophils, and iNOS expression and nitrotyrosine formation in the lung are now being examined in DEP-instilled rats.
We investigated the opsonic activity of the serum factors affecting phagocytosis of Cryptococcus neoformans in vitro to elucidate the role of humoral factors in the host defense mechanisms against ...cryptococcosis. Two strains of C. neoformans, one heavily and one weakly encapsulated, were used. Guinea pig peripheral blood leukocytes (PBLs) were used for phagocytosis. The viable weakly encapsulated cells were ingested effectively by PBLs, in the presence of guinea pig normal fresh serum, while the heavily encapsulated cells were not ingested. Neither immune serum, its IgG fraction alone, nor heated serum promoted the phagocytosis of either the weakly or heavily encapsulated strain. On the other hand, immune serum promoted adherence of PBLs to viable cells of the heavily encapsulated strain, forming rosettes in the presence of fresh serum. A substantial amount of C3b component was detected on yeast cells when weakly encapsulated cells were incubated with human fresh serum, or heavily encapsulated cells were incubated with rabbit immune serum together with human fresh serum. Serum chelation experiments also indicated that the factors involved in the alternative complement pathway are opsonins for the weakly encapsulated strain. These results suggest that the alternative pathway plays an important normal opsonic role for weakly encapsulated strains and that specific antibody plays an immune opsonic role for heavily encapsulated strains of C. neoformans via the classical pathway of complement activation.
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