After autologous stem cell transplantation (ASCT) the immunological B cell compartment recovers slowly. Delays on the recovery of B cell function after autologous stem cell transplantation are due to the low lymphocytes count and to their intrinsic dysfunction.
Methods
We studied the in vivo B cell reconstitution after ASCT examining the independent effect of polyclonal IgG (PolyIg), Fab or Fc fragments infusions in a murine animal model during a period of 12 weeks. These molecules were used in low doses, mimicking the recommended use of IVIg in the case of hypogammaglobulinemia in humans. Flow cytometry analysis and ELISA tests were conducted to monitor the reconstitution of B cells and serum immunoglobulin production. Panama blot and PCA factor 1 analysis were used to study the kinetics of immunoglobulin repertoires reconstitution. Mechanistic studies were also performed using in vitro cell culture.
Results
During follow-up after ASCT, peripheral B cells expand independently of treatment, correcting the immediate increase in sBAFF (soluble B cell activating factor) induced by previous intense myeloablation. Treatments with Fab and Fc fragments infusions promote significant IgM and IgG production comparing to control. Although the complete recovery of antibody repertoire is only achieved at the end of follow-up after ASCT, there is an earlier and significantly stronger recovery in the treated mice, which is evident at 9 weeks after ASCT. At 30 weeks after ASCT, normal values of antibody repertoire were detected in all individuals. Mechanistic studies show that Fab and Fc fragments promote IgG1 production by indirect pathways.
Conclusions
The results presented here demonstrate that polyclonal immunoglobulin indirectly improves the function of the reconstituted B cells and their IgG production by means of Fc-mediated effects on bystander cells. These results further stimulate the discussion about the advantages of IVIg therapy during immune reconstitution after human ASCT. 相似文献
Abstract Thirty-six men and women who experienced a documented myocardial infarction, half of whom ultimately died from their disease and half of whom survived over a six-year period, provided longitudinal recent life changes and ballistocardiographic data. The 18 patients who died from their coronary disease indicated a significant buildup in life changes which peaked approximately one year prior to death; their serial ballistocardiograms indicated a significant buildup in average force of contraction which was seen to peak approximately six months prior to death. The 18 post-infarction patients who survived the six-year follow-up showed neither a buildup in life change nor a buildup in the ballistocardiographic index of cardiac contraction force. These findings of a life change peak preceding ballistocardiographic evidence of an “overworked” heart are discussed in terms of their possible medical and psychophysiological significances. 相似文献
The anti-inflammatory activity of Canavalia seed lectins (Canavalia gladiata [CGL], Canavalia maritima [ConM] and Canavalia brasiliensis [ConBr]) was evaluated by intravenous administration in rats. In non-sensitized rats, cellular edema elicited by carrageenan was reduced (45–51 %) by ConM and (44–59 %) by CGL. Osmotic edema elicited by dextran was reduced by ConM and CGL in 27 % and 29 %. ConM and CGL reduced the edema elicited by l-arginine in 53 % and that of prostaglandin E2 in 48 % and 36 %. Leukocyte migration elicited by carrageenan was reduced in 49 % by ConM and in 55 % by CGL (attenuated in 4× by glucose) and peritoneal TNF-α content in 82 %. In rats sensitized, ConM inhibited the paw edema and leukocyte migration elicited by ovalbumin in 34 % and 70 %. ConM and CGL are anti-inflammatory, mainly in cellular events mediated by prostaglandin E2, nitric oxide and TNF-α in non-sensitized rats. However, only ConM is anti-inflammatory in sensitized rats. CGL effect involves the lectin domain. 相似文献
BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations.MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV).ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher.ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis. 相似文献
This study aimed to evaluate the effects of chronic consumption of cachaça, a Brazilian beverage containing alcohol, on submandibular glands (SM) of rats by using histomorphometric and biochemical parameters.
Materials and methods
Twenty-four male rats (40 days of age) were assigned into the following four groups (n = 6): two control groups for 75 days (C75) and 105 days (C105), and two experimental groups of cachaça ingestion with ascending concentrations for consecutive 75 days (CA75) and 105 days (CA105). On the right SM glands, the striated, granular and acini ducts were processed for histomorphometric analysis. The left SM glands were weighed and stored at − 80 °C, to evaluate through biochemical tests carried out by spectrophotometric methods, the functional activity of total acid phosphatase (TAP), tartrate-resistant acid phosphatase (TRAP), and alkaline phosphatase (ALP) and to determine the mucin levels.
Results
The absolute and relative weights of the SM glands in both experimental groups were reduced in relation to the controls (p < 0.05). The histomorphometric analysis showed a significant reduction of the acini area (p < 0.05) and non-relevant reduction of striated ducts (p > 0.05). The granular ducts did not show a significant increase of the area (p > 0.05). The TAP and TRAP activities were significantly decreased in the experimental groups (p < 0.05), while the ALP functional activity decreased moderately (p > 0.05). Mucin levels also had a significant reduction when compared with the control groups (p < 0.05).
Conclusions
Chronic consumption of cachaça can cause morphological changes associated with glandular atrophy, loss of biochemical functionality of phosphatases, and the reduction of mucin synthesis.
Clinical relevance
The consumption of cachaça can compromise the functions of the submandibular glands by altering their morphology and enzymatic activity.
Summary We have presented an unusual case of benign lymphoid hyperplasia, which manifested as a cecal deformity in a 15-year-old boy.
The clinical manifestation may have been related to partial occlusion of the appendiceal orifice. In future cases of benign
lymphoid hyperplasia, colonoscopy may be diagnostic, and if it is used for continuing observation, may avert unnecessary surgical
procedures in children and young adults. 相似文献