Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.     

Differentiation of blast cells from a Down's syndrome patient with transient myeloproliferative disorder

A male neonate with Down's syndrome and congenital myeloproliferative disorder was studied. His blood picture showed the unique coexistence of leukocytosis with matured cells and a large number of blast cells. The in vitro proliferation and differentiation of blast cells into various lineages in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM) was examined by using a liquid culture and a methylcellulose culture system. The differentiation of blast cells into myeloid cells was confirmed by specific cytochemical stainings, electron microscopy, and an immunologic study. No specific factors in the plasma of the patient promoted the proliferation or differentiation of blast cells. The cellular composition of colonies grown in methylcellulose culture from single blast cells was studied by a micromanipulation technique. High plating efficiency was observed. Of 136 cultures, 78 showed colony growth. Half of the blast cells were colony-forming cells that could proliferate and differentiate into basophils, neutrophils, eosinophils, macrophages, and erythrocytes in the presence of PHA-LCM. Using the blast cells with a high differentiation capacity to the basophil pathway, we studied the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM- CSF). Recombinant GM-CSF support neutrophils, eosinophils, and macrophages but not typical basophils. These findings of the cell differentiation of blast cells into various kinds of cells in vitro were in agreement with the finding of neutrophilia, eosinophilia, basophilia, and thrombocythemia in this patient.     

Muscle strength in patients with gastrointestinal carcinoma--an important role of muscle strength as a nutritional parameter

The relationship between nutritional status and muscle strength was examined in 73 patients with gastrointestinal carcinoma preoperatively. Nutritional status was assessed by measuring various nutritional parameters. Muscle strength was determined by measurements of %grip strength and respiratory muscle strength expressed as %maximal expiratory and inspiratory pressure (%MEP and %MIP). The results were as follows: %GS was significantly low in the patients who showed low values in body weight (%ideal body weight: %IBW), mid-arm muscle circumference (%AMC), serum albumin (Alb), serum prealbumin (PA), total peripheral lymphocyte count (TLC), and/or nutritional surgical risk index (NRI). %MEP was significantly low in the patients who showed low values in %IBW, %AMC, triceps skin fold, Alb, PA, retinol binding protein, NRI, and/or nutritional assessment index (NAI). %MIP was significantly low in the patients who showed low values in %IBW, %AMC, creatinine height index, Alb, PA, NRI, and/or NAI. %MEP and %MIP were significantly correlated with %GS. Preoperative %GS value was significantly low in the esophageal cancer patients with postoperative pulmonary complications. It was suggested that %GS was a simple and useful nutritional parameter for detecting depletion of the muscle mass and visceral proteins, for respiratory muscle strength, and for functional capacity of muscle.     

Augmentation and subsequent attenuation of Ca2+ current due to lipid peroxidation of the membrane caused by t-butyl hydroperoxide in the rabbit sinoatrial node.

Cellular electrophysiological effects of membrane lipid peroxidation by t-butyl hydroperoxide (TBH) were studied in the rabbit sinoatrial (SA) node. Superfusion for 1-5 min with 300 microM TBH caused an initial increase and subsequent decrease in the spontaneous firing frequency of the SA node. Voltage clamp experiments revealed that TBH initially enhanced but later blocked the Ca2+ current. Thus, membrane lipid peroxidation appears to accelerate and then suppress physiological automaticity by causing biphasic changes in the Ca2+ current.     

Selectivity of cerebral vasodilators on basilar arteries

Ca-antagonistic activities of cerebral vasodilators, nicardipine and 1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100) were tested on basilar and renal arteries, thoracic aorta and portal vein of rabbit, and rat vas deferens. Both the cerebral vasodilators used herein had a selectivity to basilar arteries. The selectivity to the basilar arteries is considered to be one of the factors in deciding the pharmacological property of the cerebral vasodilators.