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51.
52.
BACKGROUND: X-linked severe combined immunodeficiency (SCIDXI) is an inherited immune defect which leads to death in infancy from severe infections. The defect is caused by mutations of the IL-2RG gene that encodes for the common gamma chain shared by several cytokine receptors. The disease is characterised by lack of T and NK cells with normal numbers of B cells. SCIDXI can be cured by bone marrow transplantation (BMT) or prevented by abortion after prenatal diagnosis. METHODS: A male fetus was diagnosed as having SCIDXI by molecular, immunophenotypic, and functional analyses. The fetus was injected intraperitoneally under ultrasound guidance with CD34 haematopoietic progenitor cells purified from paternal bone marrow and T-cell depleted by E rosetting. Chimerism analysis was by HLA-DQ alpha typing and gamma-chain staining on cord blood. FINDINGS: A healthy 3.6 kg boy was delivered by caesarean section at 38 weeks of gestation with no clinical or laboratory signs of graft-versus-host disease. Engraftment of donor-derived CD2 cells was found at birth. At 3.5 months of age the infant is well and his T-cell counts and function are normal. INTERPRETATION: In-utero transplantation of haematopoietic progenitor cells allowed immune reconstitution of a fetus with SCIDXI and may be an alternative to elective abortion. Our report should encourage applications of this method to other inherited disorders curable by BMT.  相似文献   
53.
The objective of this study was to examine the immunotoxicological effects of the methyl-carbamate pesticide carbaryl via the oral, dermal, or inhalation routes. Male CD rats were exposed to carbaryl 5 d/wk for a 2-wk period. During nose-only inhalation exposures, rats received either 36, 137, or 335 mg/m3 carbaryl in acetone for 6 h. Air only and acetone/air controls were run concurrently. Orally exposed animals received either 1 ml corn oil or 10, 25, or 50 mg/kg carbaryl, while dermally exposed animals received either 2 ml acetone or 100, 500, or 1000 mg/kg carbaryl on their dorsal flank for 6 h. Four days prior to sacrifice, animals from all exposure groups were injected iv with 2 x 10(8) sheep red blood cells (SRBC). The primary immunoglobulin M (IgM) humoral immune response to SRBC was then assessed by measuring SRBC-specific antibody-forming cells (AFC) and levels of serum anti-SRBC IgM antibody, respectively, using the hemolytic plaque assay and an enzyme-linked immunosorbent assay. Individual body weights, spleen, thymus, and liver weights, spleen cell number, and red and white blood cell (RBC, WBC) counts were obtained for each animal. Following nose-only inhalation exposures, dose-dependent decreases in thymus weights, spleen cell number, AFC/spleen, AFC/10(6) splenocytes, and serum levels of SRBC-specific IgM antibody were observed. Significant decreases of 33, 57, and 22% in spleen cell number, AFC/spleen, and thymus weight, respectively, were found at the 335 mg/m3 exposure level. Animals exposed orally to 25 mg/kg carbaryl had a 34% decrease in WBC counts. A 34% decrease in WBC and a 13% increase in RBC counts were observed at the 50 mg/kg oral dose. Significant decreases in liver weights ranging from 11 to 13% were found at all oral exposure levels. Dermal exposure to carbaryl revealed no significant toxicological effects. Results indicate that humoral immune suppression was observed following inhalation, but not following oral or dermal exposures to carbaryl. Immunotoxicological studies evaluating pesticides need to consider relevant exposure routes and dosages for appropriate risk assessment procedures and exposure limits to be established.  相似文献   
54.
This retrospective study examined the clinical course of 18 prepubertal boys (aged 6 to 12) who had dual diagnoses of attention deficit hyperactivity disorder and conduct disorder and who received clonidine on an inpatient basis after failed trials of conventional drug therapy, consisting predominantly of psychostimulants. The effects of clonidine were assessed during inpatient treatment and after discharge at intervals of 1 to 2 months. Eleven (61%) of the children had marked improvement as measured by clinical impression. Transient sedation lasting 2 to 3 days occurred after initial administration or dosage increase; otherwise, clonidine was well tolerated. Our findings suggest that clonidine may prove to be an alternative treatment of comorbid attention deficit hyperactivity disorder and conduct disorder.  相似文献   
55.
We performed precise reticulocyte counts and a reticulocyte maturation study according to ribosomal RNA (rRNA) content, in normal cord blood. For this purpose we analyzed 35 cord blood specimens corresponding to a mean gestational age of 39.2 weeks (range 38-41). In all specimens complete blood counts were performed with the H*1 (Technicon, Bayer) analyzer. Reticulocyte maturation study and counts were conducted by the R-1000 (Sysmex) reticulocyte analyzer. We obtained the following measurements (mean +/- 1 SD): reticulocyte percentage 3.11 +/- 0.75% and reticulocyte absolute count 137.3 +/- 33.3 x 10(9)/l. There was no correlation between the reticulocyte counts and the duration of gestation or the type of labor (normal, forceps assisted or cesarean section). Reticulocyte subpopulations with different rRNA content and maturation were expressed as reticulocytes with high (HFR), median (MFR) and low (LFR) fluorescence of the fluorochrome auramine bound to rRNA. Normal cord values were: HFR% = 13.6 +/- 2.4, MFR% = 22.5 +/- 2.4 and LFR% = 63.9 +/- 4.3. Reference maturation subpopulations were assessed for comparison in 180 samples of healthy adults (90 males and 90 females) and were found HFR% = 1.0 +/- 0.8, MFR% = 9.7 +/- 3.3 and LFR% = 89.2 +/- 3.4. The HFR% and MFR% were significantly higher while LFR% was significantly lower (p < 0.001) in cord compared to adult blood, denoting a shift to more immature reticulocyte forms. The above values are provided as normal reference data of the reticulocyte maturation profile in full-term cord blood.  相似文献   
56.
BACKGROUND: The effects of hypothermic injury to the liver were investigated on an isolated perfusion circuit by comparing porcine livers with varying degrees of preservation injury. METHODS: A group of unstored livers (n = 5) were compared to livers stored in University of Wisconsin (UW) solution for 18 h (n = 5), and a group of livers stored in Hartmann's solution for 18 h (n = 5). RESULTS: We observed that the degree of platelet sequestration was directly related to the severity of the preservation injury. After 2 h of isolated liver perfusion, the perfusate platelet count fell from 148 +/- 14 x 10(9)/L to 84 +/- 13 x 10(9)/L for control livers. In comparison for livers stored in UW solution, the platelet count fell from 173 +/- 43 x 10(9)/L to 61 +/- 14 x 10(9)/L representing a 64.8% fall, while for those stored in Hartmann's solution, an even more profound fall from 152 +/- 36 x 10(9)/L to 19 +/- 9 x 10(9)/L (87.5% fall) was observed. The difference between the UW-stored and Hartmann's-stored livers was significant (P < 0.05). However, using this model, the degree of leukocyte sequestration did not differentiate the groups. Both histological and ultrastructural examination of liver biopsies taken immediately following revascularization demonstrated that for mild degrees of preservation injury following hypothermic storage, changes occur to the sinusoidal lining cells well before changes to the parenchymal elements. CONCLUSIONS: These findings substantiate the hypothesis that the primary injury associated with hypothermia involves the sinusoidal lining cells (non-parenchymal elements), that it is predominantly a reperfusion phenomenon and that efforts at improving preservation should therefore be targeted primarily at these cells and not the hepatocytes.  相似文献   
57.
BACKGROUND AND OBJECTIVE: Spectroscopic guidance of laser angioplasty has been attempted using a diagnostic He-Cd laser in addition to the therapeutic laser system. This study evaluated a single-laser approach for simultaneous ablation and fluorescence excitation. STUDY DESIGN/MATERIALS AND METHODS: A spectroscopy system was coupled to a clinical XeCl excimer laser. Ablation of 162 human aortic samples in saline and blood with 45 mJ/mm2 per pulse yielded 676 fluorescence spectra validated histologically. The same equipment was used in 16 patients for angioplasty of 18 coronary stenoses applying 500 to 1,725 pulses with 45 to 60 mJ/mm2 under saline flushing. A total of 783 spectra were recorded and validated by intracoronary ultrasound (categories: atheroma, fibrous plaque, calcified lesion). RESULTS: In vitro, 5 types of spectra could be differentiated: (1) atheroma, (2) fibrous plaque, (3) calcified lesion in saline, (4) media, and (5) calcified lesion in blood. Discriminant analysis prospectively classified 576 validation spectra with the following sensitivity and specificity for each type: (1) 83.5 and 97.1%, (2) 85.7 and 96.8% (3) 100 and 98.5%, (4) 98.1 and 99.3%, (5) 98.9 and 100%, respectively. In vivo type 1, 2, 3, and 5 spectra were also observed, but not the media spectrum. The predominant sonographic category also prevailed in spectroscopy. Calcified lesions yielded type 3 and 5 as well as mixed spectra. CONCLUSIONS: Using an excimer laser for angioplasty allows combining ablation and fluorescence excitation without a diagnostic laser. Principal types of atherosclerotic lesions and the media can be differentiated spectroscopically with this approach.  相似文献   
58.
Autoantibodies to the thyrotropin receptor (TSHR) can act as thyrotropin agonists or antagonists, or can cause thyroid hypertrophy. Neither the autoantibody-binding sites on the TSHR nor the intracellular mechanisms by which the autoantibodies mediate their diverse functional effects are completely understood. This article reviews how cloning of the TSHR has contributed to our understanding of its structure and function, and has allowed induction of experimental autoimmunity to the TSHR.  相似文献   
59.
Four B. fragilis strains were examined: one nonenterotoxigenic (NTBF) and three producing enterotoxin (ETBF). The growth of cultures was determined and enterotoxin, which is released to the culture medium during growth of strains, was detected. BHI broth and BHI broth with addition of subinhibitory doses (sub-MIC) of clindamycin were applied. Bacterial cultures were incubated at 37 degrees C for 48 hours. After 4, 8, 16, 24, 48 hours of cultivation, samples of bacterial cultures were collected and the optical density was measured. Then the samples were centrifuged, supernatants were filtered through 0.45 micron filters and concentrated three times with 5000 D ultrafilters. Prepared samples were kept frozen at -70 degrees C until used. The titre of enterotoxin in samples was determined on human colon adenocarcinoma cell line HT 29/C1. Neutralization assay was performed with culture filtrates, which were enterotoxin-positive and with rabbit anti-enterotoxin serum. The results of the experiments indicate that enterotoxin is detected after 16 hours of incubation of ETBF strains. Clindamycin at subinhibitory concentrations (sub-MIC) inhibits the growth of B. fragilis cultures. The antibiotic causes also delay and decrease in enterotoxin production by ETBF strains.  相似文献   
60.
In rats carbaryl undergoes extensive biotransformation involving both albumin-mediated hydrolysis and cytochrome P-450-mediated metabolism; studies have suggested that approximately one-half of a carbaryl dose is hydrolysed and one-half is metabolized. Fluosol is known to be an inducer of cytochrome P-450, and Fluosol haemodilution reduces plasma albumin concentrations. The disposition of carbaryl was, therefore, determined in rats for 72 h after 40 mL kg-1 haemodilution with Fluosol or normal saline (0.9% NaCl). Volumes of distribution were significantly reduced after saline haemodilution for 72 h but only at 48 h after Fluosol haemodilution. Fluosol and saline haemodilution had little influence on carbaryl total body clearance (CL). These results indicate that both hepatic and non-hepatic clearance pathways were not influenced by the haemodiluents or the haemodilution procedure.  相似文献   
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