Tumor necrosis factor-alpha downregulates protein S secretion in human microvascular and umbilical vein endothelial cells but not in the HepG- 2 hepatoma cell line

Protein S deficiency, which is associated with thrombosis, can either be inherited or acquired. Recently, we reported that a decrease in free protein S was observed in 19 of 25 persons with HIV/AIDS. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been reported to be elevated in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and has been shown to induce a procoagulant state on the surface of endothelial cells. We report here that recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the SV-40T transfected human microvascular endothelial cell line (HMEC-1) model system by approximately 70% and in primary human umbilical vein and dermal microvascular endothelial cell cultures by approximately 50%. Using the HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at 24 hours that was corroborated by Western blot analysis and enzyme- linked immunosorbent assay (ELISA) quantification. Evidence supporting the specificity of the TNF-alpha effect included the following: (1) TNF- alpha down-regulation of protein S was completely blocked by TNF neutralizing antibody; (2) the effect was transient, and protein S was restored to near normal levels after TNF was removed from cell cultures; (3) an antibody directed to the TNF RI (55-kD receptor) was shown to mimic the action of TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines, interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S secretion. However, TNF-alpha showed no regulatory control over protein S synthesis in the human hepatocellular carcinoma cell line HepG-2. We suggest that TNF-alpha downregulation of protein S may be a mechanism for localized procoagulant activity and thrombosis recently reported in some AIDS patients with associated protein S deficiency.     

Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction

A murine model of bone marrow (BM) transplantation in which donor (B10.D2) and recipient (BALB/c) mice were major histocompatibility complex (MHC) (H-2d) and Mls-1 identical, but incompatible at multiple non-MHC minor histocompatibility (H) antigens, and at Mls-2,3 was used to examine regeneration of B-cell development during the minor H antigen graft-versus-host reaction (GVHR). Mice that received T-cell- depleted allogeneic BM regained significant pre-B cells (sIg- 14.8+) in their BM. Mice undergoing GVHR after transplantation with allogeneic BM + T cells had less than 2% pre-B cells in their BM at day 7 and only 12% to 14% pre-B cells at days 21 and 28 compared with greater than 20% pre-B cells in the allogeneic controls. After partial recovery, the pre- B cells in the BM of GVH mice again decreased to less than 3% by day 42. This abnormal pattern of pre-B cell development in mice undergoing GVHR was associated with a reduced response to interleukin-7 (IL-7) in vitro. The delay in B-lineage cell reconstitution in mice with GVHR correlated with the expansion of donor V beta 3+ T cells in both the spleen and BM. BM T cells from mice with GVHR as well as isolated V beta 3+ T cells inhibited IL-7 colony-forming units from normal BM in co-culture assays. This inhibition could be reversed with anti- interferon gamma (IFN gamma) antibody. These data suggest that the delay in appearance and the reduction in proportion and number of pre-B cells observed early during the GVH reaction in this model is caused, in part, by the inhibitory actions of IFN gamma derived from donor V beta 3+ T cells on B-lineage cell development.     

Metabolic and energy balance in small- and appropriate-for-gestational-age, very low-birth-weight infants

This study compared nutrient utilization and postnatal weight gain composition in eight appropriate for gestational age (AGA: birth weight 1293 ± 107 g; gestational age 28.8 ± 1.4 weeks) and eight symmetrically growth-retarded (SGA: birth weight 1110 ± 230 g; gestational age 32.7 ± 1.9 weeks), very low-birth-weight (VLBW) infants. There was no significant difference in protein, mineral and energy intake between AGA and SGA infants. Nitrogen absorption (84 ± 3 and 83 ± 4%) and nitrogen retention (356 ± 48 and 352 ± 43 mg/kg/day) were similar in both groups. Fat absorption tended to be lower in AGA (78 ± 15%) than in SGA (87 ± 4%) infants. Calcium, phosphorus and magnesium absorptions were similar in AGA and SGA infants. Metabolizable energy utilization was similar in both groups; about 55% was expended and 45% stored in new tissues. Energy expenditure was 58 ± 4 kcal/kg/day in SGA infants and 61 ± 9 kcal/kg/day in AGA infants. Weight gain and its composition were similar in both groups. We conclude that nutrient and energy utilization are similar in AGA and symmetrically growth-retarded, VLBW infants.     

Whole body bone mineral content in healthy children and adolescents

Data from healthy children are needed to evaluate bone mineralisation during childhood. Whole body bone mineral content (BMC) and bone area were examined by dual energy x ray absorptiometry (Hologic 1000/W) in healthy girls (n = 201) and boys (n = 142) aged 5-19 years. Centile curves for bone area for age, BMC for age, bone area for height, and BMC for bone area were constructed using the LMS method. Bone mineral density calculated as BMC/bone area is not useful in children as it is significantly influenced by bone size. Instead, it is proposed that bone mineralisation is assessed in three steps: height for age, bone area for height, and BMC for bone area. These three steps correspond to three different causes of reduced bone mass: short bones, narrow bones, and light bones.     

Community-acquired Staphylococcus aureus bacteraemia in patients who do not abuse intravenous drugs

Despite advances in antimicrobial therapy and intensive care support, Staphylococcus aureus continues to cause significant morbidity and mortality. We studied community-acquired S. aureus bacteraemia in a population where intravenous drug abuse is extremely uncommon, prospectively reviewing all such patients (n = 113) admitted to Groote Schuur Hospital from February 1986 to January 1991. Overall mortality was 35%. Factors associated with poor outcome were: confusion on presentation, failure to mount a febrile response, acute renal failure, adult respiratory distress syndrome, shock, endocarditis, disseminated intravascular coagulation and platelet count of < 100 x 10(9)/l. Only confusion, acute renal failure and shock were independently associated with death by stepwise regression analysis. Skin infections were the most commonly identified source of bacteraemia (22%), but in 58% of patients the source was not determined. Twenty-six percent of patients were diabetic. Almost all patients (90%) developed one or more complications. In those who survived, therapy was generally prolonged, with a median of 70 days and range of 7-393 days, depending on the associated complications. Community-acquired S. aureus bacteraemia is a serious condition associated with a high complication rate and mortality.      

Diffuse pulmonary opacification in infants undergoing extracorporeal membrane oxygenation: clinical and pathologic correlation

Diffuse pulmonary opacification is commonly seen on chest radiographs from infants with severe respiratory failure treated with extracorporeal membrane oxygenation (ECMO). The chest radiographs and clinical records of 18 such infants were reviewed to determine the correlation among degree of abnormality on chest radiograph (as determined by a radiographic score), clinical severity of disease (as measured by ECMO requirements [ECMO flow rate]), and dynamic lung compliance determinations. Increasing lung compliance and decreasing ECMO flow rates correlated well with decreasing (improving) radiographic score. Pathologic changes were mainly those associated with intensive respiratory support and the underlying pulmonary condition. One patient had diffuse pulmonary hemorrhage. Other than bleeding, no distinctive pathologic features could be attributed to therapy with ECMO. We conclude that the degree of pulmonary opacification seen in infants undergoing ECMO therapy is an accurate reflection of markedly decreased lung compliance and lung volumes caused by hyaline membrane formation, pulmonary edema, and atelectasis associated with the various causes of severe respiratory failure.     

Postoperative hysterosalpingogram: radiographic-surgical correlation

The hysterosalpingograms of 46 patients who underwent previous uterine or tubal surgery were reviewed. Surgical procedures performed included cesarean section, myomectomy, uterine septal repair, tubal reimplantation and reanastomosis, and fimbrioplasty/cuff salpingostomy. The procedures and their resulting hysterosalpingographic appearances are discussed.