Protein-calorie malnutrition impairs host defense against Candida albicans.

Protein-calorie malnutrition (PCM) impairs immune responsiveness predisposing to Candida albicans sepsis, but mechanisms are unclear. This study examined the effect of PCM on enteric-derived C. albicans intestinal translocation and the ability of in vivo interferon-gamma (IFN-gamma) to upregulate macrophage (MO) candidacidal mechanisms in PCM mice. Control (24% casein) and low protein (2.5%) diets were given for 4 weeks. Mice (n = 160) were fed C. albicans in their drinking water for 3 days and C. albicans translocation (mean colony-forming units (CFU)/g tissue +/- SEM) to the GI tract, liver, spleen, and kidney was assessed at 1 and 5 days following endotoxin challenge of 1, 5, and 10 mg/kg body wt. In a separate study (n = 100 mice), IFN-gamma (1000-10,000 U/day ip) vs saline was given for 3 days prior to harvesting peritoneal macrophages for assay of superoxide anion (O2-), percentage macrophage phagocytosis of C. albicans, and percentage killing of C. albicans. On Day 1, fungal translocation to the intestinal wall and systemic organs in the PCM group was significantly higher. On Day 5, mean CFU were significantly higher in the PCM group, indicating impaired organ clearance. Mean O2-, phagocytosis, and killing were significantly impaired in the PCM group (P less than 0.05), but IFN-gamma improved all functions. PCM significantly depressed host responses to C. albicans. IFN-gamma treatment enhanced candidacidal mechanisms, suggesting a therapeutic role in the malnourished host predisposed to C. albicans sepsis.     

Children's productions of the affix -ed in past tense and past participle contexts.

Children's productions of the affix -ed in past tense and past participle contexts (e.g., the boy kicked the ball vs. the ball was kicked) were examined in spontaneous conversations and elicited productions. The performances of 7 children with specific language impairment (SLI) were compared with those of 2 control groups of typically developing children (age matches, MLU matches). Children with SLI produced fewer obligatory contexts for both past tense and past participle forms than did the control children, and were more likely to omit past tense affixes. In contrast, few omissions of the past participle were observed across all 3 groups. Implications for theories regarding the morphological deficits associated with SLI are discussed.     

Uveitis and immune responses in primates immunized with IRBP-derived synthetic peptides

Monkeys immunized with bovine IRBP-derived synthetic peptides R4 (sequence 1158-1180) or R14 (1169-1191) developed EAU which was detected by both clinical and histological examinations. The inflammation localized mainly in the choroid, with only minor changes being noticed in the adjacent retinal tissue. EAU developed in only one of the two monkeys immunized with each of the peptides and the animals with disease also showed higher levels of cellular immunity toward the immunizing peptide than did the monkeys with no disease. The cellular immune responses, measured by the lymphocyte proliferation assay, were specific toward the immunizing peptides, with no cross responsiveness to whole IRBP. This finding suggests that the two uveitogenic peptides were non-immunodominant in the tested monkeys. In contrast, peptide R14 is highly immunodominant in the Lewis rat. Also, the fine specificity of the monkey response to R14 differed from that of the Lewis rat. The possible genetic control of the monkey susceptibility to EAU induction by the peptides is discussed and the unique finding of an autoimmune disease induction by a non-immunodominant peptide is underscored.     

A prospective study of the effectiveness of brief professionally-led support groups for infertility patients.

OBJECTIVE: This study prospectively evaluates the effectiveness and patient acceptability of professionally-led support groups in alleviating psychologic distress in infertility patients. METHOD: Sixty-four consecutive patients in a university hospital infertility program were administered a battery of psychologic tests before and after attendance at an 8 weekly session support group. The comparison group consisted of 35 consecutive infertility referrals to the same unit who were not initially offered the support group and were similarly tested over an 8 week period. RESULTS: Support group patients had significantly greater (p less than or equal to 0.01) entry than exit scores on several measures of psychologic distress and depression (the Beck Depression Inventory, the Hamilton Rating Scale for Depression, and the Global Severity Index, Anxiety, Depression, Hostility and Obsessive Compulsive Subscales of the Brief Symptom Inventory). The Avoidance Coping Style on the Moos Coping Responses Inventory was correlated with a higher Global Severity Index (p less than or equal to 0.01). Comparison group patients had similar psychometric scores to the support group patients at entry but showed no change over 8 weeks. Attenders expressed a high rate of satisfaction with the support group. CONCLUSIONS: Professionally-led support groups are a highly acceptable and effective intervention in self-referred patients in alleviating psychological distress related to infertility.     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Effects of laparotomy on systemic macrophage function.

Surgical trauma induces immunosuppression that may adversely influence survival. This study examined the effect of laparotomy on two different macrophage populations, peritoneal macrophages (PM phi) and Kupffer cells. Female, 6- to 8-week old, CFW/C3H-HeN mice (n = 160) were randomly allocated to one of three study groups: control, ether anesthetic only, or ether anesthetic and laparotomy. On postoperative days 1 and 3, PM phis and Kupffer cells were harvested and assayed for superoxide anion production (O2-), percent macrophage phagocytosis of Candida albicans (CAP), percent C. albicans killed by macrophages (CAK), percent major histocompatibility complex (MHC)-class II antigen expression, and antigen presentation. Macrophages isolated on postoperative day 1 were also cocultured with 100 units/10(6) cells/ml interferon-gamma (IFN-gamma). Laparotomy significantly impaired microbicidal activity (O2-, percent CAP, and percent CAK) and antigen presentation on postoperative day 1. On postoperative day 3, O2- and antigen presentation were increased significantly (p less than 0.05) over control values, indicating a rebound phenomenon. Kupffer cell microbicidal function was unchanged on postoperative days 1 and 3. The initial immune impairment (PM phis: O2-, CAP, and CAK) was abrogated by IFN-gamma treatment. In immunosuppressed hosts after injury, administration of macrophage-activating factors such as IFN-gamma could be of therapeutic benefit.     

Oxygen consumption following trauma: a reappraisal in severely injured patients requiring mechanical ventilation

Oxygen consumption (VO2) immediately following major injury in man has been said to be reduced. The evidence for this is poor. We have therefore measured VO2 soon after major injury in 16 patients. VO2 was reduced in only two patients, within the normal range in four and increased in ten. VO2 was maintained by increased oxygen extraction in six patients leading to low levels of mixed venous oxygen saturation. There is no evidence for an 'ebb phase' response in man.     

Bone disorders following total gastrectomy

Bone disorders following gastrectomy were studied by measuring absolute and relative bone mineral density of the Wards triangle, serum 1,25-(OH)₂-D, alkaline phosphatase, and total serum calcium. The subjects were 20 males who had undergone total gastrectomy not more than three months previously (group A₁). Seventeen of these patients were reviewed three years later (group A₂). Absolute and relative bone density were significantly lower in group A₂ than in A₁ (0.52 ± 0.011 g/cm² versus 0.6 ± 0.014 g/cm²,P<0.01 and 85.5 ± 1.4% age-matched control versus 95 ± 1.3%,P<0.01). 1,25-(OH)₂-D was significantly lower in group A₂ than in group A₁ (14.3 ± 0.97 pg/ml versus 20.6 ± 1.02 pg/ml,P<0.01). There was no difference in alkaline phosphatase and calcium serum concentration. The mean weight loss was 6.26 ± 0.57% over the follow-up period, and weight loss correlated with absolute and relative bone density (r=–0.74,P<0.01). There was a positive correlation between 1,25-(OH)₂-D and absolute or relative bone density (r=0.67,r=0.62 andP<0.01). These data suggest that bone density decrease has already occurred three years after total gastrectomy and is positively correlated to 1,25-(OH)₂-D deficiency. As no differences in serum alkaline phosphatase and serum calcium concentration were found, these factors are of little value for the early detection of postgastrectomy bone disorders, whereas weight loss is a valuable screening parameter.