Bone marrow transplantation (BMT) is the only known cure for a variety of inherited diseases and requires the administration of high doses of immunosuppressive and myeloablative therapy. Because the ...fetus is immunoincompetent early in gestation, in utero stem cell transplantation (IUT) could avoid the need for this toxic conditioning. A major limitation to date of IUT is the low level of engraftment and failure to induce tolerance. Dendritic cells (DC) are considered very potent antigen-presenting cells, but DC progenitors (pDC) are strongly tolerogenic.
We examined the effect of donor pDC on the degree of engraftment and tolerance induction after IUT. Bone marrow-derived pDC (CD80low, CD86-) from male C57BL/6 mice (H2b) were injected with and without donor bone marrow (BM) intraperitoneally into 13 to 15-day BALB/c (H2d) fetuses. Engraftment was determined by flow cytometry and quantitative polymerase chain reaction and tolerance by skin grafts and the mixed lymphocyte reaction.
At 1-month posttransplant, mice that received BM+pDC showed a higher degree of engraftment (29+/-46%) than mice that received pDC-enriched cells or BM cells alone (0.11+/-0.70% and 1.71+/-1.66%, respectively, P<0.001). However, 5/19 recipients of BM+pDC died within 6 weeks; 4/5 had significant donor cell engraftment in blood and/or tissues. Also, these mice had evidence of graft-versus-host disease (GVHD). Two mice out of 15 long-term survivors in the BM+pDC group had virtually complete replacement of host with donor hematopoietic cells. Skin grafts and mixed lymphocyte reaction studies showed no durable tolerance induction other than in the two fully engrafted recipients of BM+pDC.
These results suggest that donor pDC, along with donor BM, can have a significant impact on engraftment of MHC-mismatched donor cells associated with an increased incidence of GVHD. However, marrow-derived pDC do not result in an increase in tolerance induction in utero even when microchimerism is present.
Sclerosing mesenteritis is a rare condition that involves the small or large bowel mesentery. An unusual presentation of this condition, which led to difficult preoperative assessment and diagnosis, ...is described. This report is followed by a comprehensive review of the literature.
To evaluate the differences in sleep of women throughout pregnancy compared with those of nonpregnant control subjects.
Four pregnant women were studied longitudinally during their pregnancy using ...inpatient polysomnography. Measurements included electroencephalography, electrocardiography, and continuous-pulse oximetry. Four healthy nonpregnant women matched for age and weight were used as control subjects. The total sleep time was recorded, and percentages of each sleep stage were generated.
Qualitative differences in sleep between pregnancy patients and control subjects were evident. Control subjects displayed a normal appearance of slow-wave sleep in stages 3 and 4 (delta sleep). When pregnant patients did display delta sleep, it appeared abnormal secondary to extensive alpha-wave intrusion. Even when including this abnormal delta sleep in a quantitative comparison, the pregnant patients had a significantly shorter percentage of total sleep time in delta sleep (4.9+/-1.9% vs 21.9+/-6.0%, p=0.03).
Sleep in pregnancy is characterized by loss of normal slow-wave sleep. Thus, sleep stages 3 and 4 are shortened during pregnancy. This sleep alteration is persistent when followed longitudinally during pregnancy.
BACKGROUNDPoor linear growth frequently complicates chronic inflammatory bowel disease in children. Circulating inflammatory mediators may play a role in this growth delay. We evaluated the effect of ...experimental colitis on bone growth in a nutritionally controlled rat model.
METHODSExperimental colitis was induced in male Sprague-Dawley rats (125-150 g) by enema with trinitrobenzene sulfonic acid in 50% ethanol on day 1 and 11 of a 14-day protocol. Control animals were pair-fed and all animals received a liquid rat diet (1 kcal/ml). Twenty-four-hour urine, collected on days 2 and 12 and serum samples, collected at death, were analyzed for calcium, zinc, and magnesium. Serum samples from a separate set of animals were studied for serial interleukin-6 levels. Right proximal tibias were processed for growth-plate histo-morphometry, in which linear growth is proportional to the heights of the proliferative zone, and terminal hypertrophic chondrocyte, but inversely proportional to the height of the resting zone.
RESULTSHistology confirmed active inflammation in the animals given trinitrobenzene sulfonic acid. Weight gain and both urinary excretion and serum levels of zinc, calcium, and magnesium did not differ between treatment and nontreatment groups. Histologically, there was impaired linear bone growth. The resting zone was greater in the colitis group (94.5 ± 32.6 μm versus 3.9 ± 5.4 μm; p < 0.05); the proliferative zone was smaller in the colitis group (123.7 ± 18.2 μm versus 78.9 ± 11.2; p < 0.05 μm); the terminal hypertrophic chondrocyte was reduced in the colitis group (19.5 ± 1.4 μm versus 28.8 ± 3.6 μm; p < 0.05). At 6 and 24 hours after induction, the level of interleukin-6 was elevated in the colitis group.
CONCLUSIONSExperimental colitis results in a decreased linear bone growth, independent of nutritional intake. Circulating cytokines derived from intestinal inflammation may contribute to the suppression of bone growth.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The plasma polymerization of hexamethylcyclotrisiloxane (D3) and octamethylcyclotetrasiloxane (D4) over the microporous polypropylene membrane Celgard 2400, over polypropylene filter membranes, and ...over glass slides was investigated. The rate of polymer deposition was dependent upon the location of the substrate materials in the reaction vessel. The increase in weight of all the substrates was linear with the time of reaction, indicating a uniform polymerization rate. The rate of polymer deposition over polypropylene filters was found to be 2.27 micrograms/cm(2)/min for both D3, and D4, whereas over the glass slides it was 1.53 and 1.87 microgram/cm(2)/min for D3 and D4, respectively. The coated Celgard membranes showed better blood compatibility that Silastic sheeting or glass.
The specificity of vesicular transport is regulated, in part, by the interaction of a vesicle-associated membrane protein termed synaptobrevin/VAMP with a target compartment membrane protein termed ...syntaxin. These proteins, together with SNAP-25 (synaptosome-associated protein of 25 kDa), form a complex which serves as a binding site for the general membrane fusion machinery. Synaptobrevin/VAMP and syntaxin are ubiquitously expressed proteins and are believed to be involved in vesicular transport in most (if not all) cells. However, SNAP-25 is present almost exclusively in the brain, suggesting that a ubiquitously expressed homolog of SNAP-25 exists to facilitate transport vesicle/target membrane fusion in other tissues. Using the yeast two-hybrid system, we have identified a 23-kDa protein from human B lymphocytes (termed SNAP-23) that binds tightly to multiple syntaxins and synaptobrevins/VAMPs in vitro. SNAP-23 is 59% identical with SNAP-25. Unlike SNAP-25, SNAP-23 was expressed in all tissues examined. These findings suggest that SNAP-23 is an essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion in all mammalian cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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