ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Human recombinant erythropoietin (r-HuEPO) was given i.v. to rhesus monkeys to compare its safety, erythropoietic effects, and pharmacokinetics in healthy adult and infant animals. Eighteen adult and 18 infant (9- to 15-d-old) monkeys were divided into three groups each of six animals. One group was given 250 U/kg twice weekly, another was given 100 U/kg twice weekly, and a control group was given the drug vehicle for 6 wk. All animals were healthy throughout this period, and for 10 wk after that. Administration of r-HuEPO at these dosages did not produce any changes in leukocytes, platelets, urea nitrogen, bilirubin, creatinine, alkaline phosphatase, alanine amino transferase, γ-glutamyl transferase, and blood pressure in either age group. At 6 wk, both adult treatment groups had statistically significant increases in Hb concentration. The same dosages that produced these increases in Hb concentration in adults produced no changes in Hb concentration in infant monkeys. Despite active erythropoiesis, as determined by reticulocytosis and increased total body Hb, Hb concentration decreased similarly in the infant treatment and control groups. Pharmacokinetic profiles were obtained at 5 wk of dosing. One h after administration, both doses of r-HuEPO produced significantly lower serum r-HuEPO concentration in the infant monkeys compared with the adults. These differences appeared to be due to a larger volume of distribution of r-HuEPO in the infant monkeys. The t½of r-HuEPO in circulation was the same in both age groups.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The cytolytic function of natural killer (NK) cells and their responsiveness to interferon-α and IL-2 were investigated in children with acute lymphoblastic leukemia (ALL) using51Cr-release and single-cell assays. For comparison, such NK cell functions were similarly assayed in neuroblastoma. NK activity in ALL children was extremely low at onset, but it increased gradually during remission and finally reached normal levels. At the single-cell level, their NK cells at onset were defective in the binding, lytic, and recycling abilities. Although the binding and lytic defects improved to normal levels during remission, the recycling, which increased gradually during remission, was still low even after the long-term remission in ALL: the maximal recycling capacity values were 1.9 ± 0.4 (p< 0.001) at onset and 4.6 ± 0.6 (p< 0.05) after 5 y of complete remission, as compared to the value in control children of 5.4 ± 0.7. On the other hand, children with neuroblastoma had no recycling defect after completing the therapy: their maximal recycling capacity value was 5.6 ± 0.7. Bone marrow cells in ALL were also depressed in their recycling ability at all stages. Interferon-α and IL-2 could enhance NK activity and IL-2 could generate lymphokine- activated killer activity at all stages of ALL; however, the recycling defect hardly improved with these treatments. Thus, NK cells in childhood ALL have a recycling defect as a functional characteristic.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We studied the numbers of T-cell receptor α/β- and γ/δ-bearing lymphocytes in 27 jejunal specimens from 19 celiac patients, 27 rectal and colonic specimens from 14 ulcerative colitis patients and four patients with Crohn's disease, and 24 control specimens. MAb and a three-layer peroxidase staining method were used. Only low numbers of γ/δ+ cells were seen in normal jejunum and rectum of controls, as well as in the specimens of patients with inflammatory bowel diseases. In the lamina propria of celiac patients, the mean number of γ/δ+ cells was significantly higher than in the controls before treatment, during gluten-free diet, and after the gluten challenge. Within the jejunal epithelium, the number of γ/δ+ cells was elevated before and during gluten elimination and after the challenge test. The absolute number of intraepithelial γ/δ+ cells remained constant during gluten elimination and provocation. We infer that the constantly elevated population of γ/δ+ T cells in the epithelium of celiac patients may play an important role in the pathogenesis of celiac disease.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Study was made of immune responses in cow's milk allergy by a new immunoassay that measures total Ig-secreting cells and specific antibody-secreting cells during their maturation cycle in peripheral blood. These primed gut-associated lymphoid tissue-derived lymphocytes are assumed to reflect the intestinal immune responses. During diagnostic milk provocation, 15 patients had acute urticarial skin eruptions, eight patients had slow onset of eczema, and 15 showed symptoms from the gastrointestinal tract. A significant increase in IgM-secreting cells (means with 95% confidence intervals) from 382.2 (265, 552) to 621.4 (381, 1013)/106cells,p< 0.01, but not IgA- and IgG-secreting cells was associated with acute urticaria. In patients with eczematous skin eruptions and gastrointestinal symptoms, the response involved all these Ig isotypes. The magnitude of the postchallenge Ig-secreting cell responses in patients with gastrointestinal symptoms in the IgM class [from 657.9 (428, 1012) to 3544.0 (1696, 7406)/106cells,p<0.001] and the IgA class [from 974.6 (590, 1610) to 2482.4 (1528, 4028)/106cells,p=0.001] significantly exceeded that of the patients with cutaneous symptoms. Notwithstanding the distinct increase in the total number of Ig-secreting cells, the specific antibody- secreting cell response specifically directed against β-lactoglobulin and α-casein was small and inconsistent. These findings indicate that immune exclusion of milk antigens is defective in cow's milk allergy. The quality and extent of the response varied in the three reaction types, suggesting that different immunopathogenic mechanisms are operative in cow's milk allergy.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Anion transport in sickle cells (SS RBC) mediated by the band 3 membrane protein was evaluated by three different measures in both oxygenated and deoxygenated conditions and compared to normal red cells. First, Cl-self-exchange measured as36Cl-efflux at 0°C was normal in SS RBC in both Vmaxand dependence on extracellular Cl-concentration. There was no effect of deoxygenation on either parameter. Second, stilbene-sensitive35SO=4:SO=4exchange, measured at 37°C where morphologic sickling occurred, was also unaffected by deoxygenation and was normal compared to normal red cells. Third, conductive Cl-flux was assessed by measuring the rates of Cl-limited K+efflux in valinomycin-treated cells at 37°C. Both the stilbene-sensitive and insensitive components of net Cl-flux were similar in SS RBC and normal red cells, and were unaltered by morphologic sickling. Thus, despite dramatic alterations in cation transport in SS RBC and the demonstration of interaction between band 3 protein and sickle cell, anion transport functions appear to be normal in SS RBC and are unaffected by deoxygenation. These data suggest that the majority of the anion exchangers in SS RBC are functionally normal.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Our studies were designed to characterize calcium transport by intestinal Golgi vesicles in spontaneously hypertensive rats (SHR) and their genetically matched control, Wistar-Kyoto rats (WKY). The biochemical purity of the intestinal Golgi in SHR and WKY was validated by marker enzyme studies. Calcium uptake by Golgi vesicles represented transport into the intravesicular space as evidenced by temperature dependency and by calcium ionophore A23187-induced calcium efflux experiments. ATP-driven calcium uptake was stimulated severalfold compared with uptake in the absence of ATP and adenylyl-(β-γ-methylendiphosphate) (nonhydrolyzable ATP) in both SHR and WKY. ATP-dependent calcium uptake was significantly higher in WKY compared with SHR at early times points, 15 s-5 min (p< 0.05–0.01). The initial rate of calcium uptake was linear up to 60 s. Kinetic parameters of calcium uptake at free calcium concentrations of 0.1 to 2.0 µM showed a Vmaxof 1.64 ± 0.06 and 1.2 ± 0.06 nmol.mg protein−1.15 s−1in WKY and SHR, respectively (p< 0.01), and the Km values were 0.17 ± 0.03 and 0.16 ± 0.04 µM, respectively. Kinetic analysis of ATP-dependent calcium uptake in 3-wk-old rats showed a Vmaxof 0.07 ± 0.005 and 0.36 ± 0.05 nmol/ mg protein−115 s−1(p< 0.01) and a Km of 0.26 ± 0.08 and 0.4 ± 0.2 nM in SHR and WKY, respectively. These results suggest that intestinal Golgi vesicles in SHR and WKY demonstrate an ATP-driven calcium uptake. This ATP-dependent process is significantly decreased in the weanling and adult SHR compared with WKY. Such an abnormality in intracellular calcium regulation may have a role in the development of hypertension.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Experimentally-induced oligohydramnios (oligo) produces lung hypoplasia. To determine if arginine vasopressin (AVP), a hormone known to decrease fetal lung fluid production, contributes to the pathogenesis of oligo-induced lung hypoplasia, the following experiment was performed. Brattleboro rats were mated to produce litters either with AVP [heterozygotes (HZ)] or without AVP [homozygotes (HO)]. On d 15 of gestation, half of each litter underwent amniocentesis to create persistent oligo. Littermates with intact membranes served as controls. Four groups of fetuses,i.e10 HO litters divided into control (44 fetuses) and oligo (25 fetuses), and eight HZ litters divided into control (35 fetuses) and oligo (18 fetuses), were killed at term for measurement of organ weights and biochemical determination of lung development. Significant differences between control and oligo groups were observed for body weight (HO,p= 0.008; HZ,p= 0.03), lung weight (<0.001 for both crossings), lung/body weight ratio (<0.001 for both), DNA per lung (HO,p= 0.02; HZ,p< 0.001), and lung dry/wet ratio (HO,p< 0.001; HZ,p= 0.001). Oligo groups with and without AVP were not found to be different for lung weight (p= 0.217), lung/body weight ratio (p= 0.209), and DNA per lung (p= 0.822). An analysis of variance confirmed the lack of any significant difference of the impact of oligo in the presence or absence of AVP. We conclude that AVP plays no role in the development of oligo-induced lung hypoplasia.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID