Induction of HLA-specific CTL to nonimmunogenic, heat-inactivated lymphocytes by interleukin 2

Human lymphocytes that have been heat-inactivated (1 hr, 45 degrees C) were used as stimulator cells in a model system to study the requirements of allogeneic T cell activation in vitro. Cytotoxic T lymphocytes were not generated in either primary or secondary mixed lymphocyte cultures after exposure to heated stimulator cells. Successful reconstitution of cytolytic activity in primary cultures was achieved by the addition of rIL-2. Further, cytotoxic T cell lines could be maintained in culture for several weeks by stimulation with heated allogeneic cells and periodic addition of exogenous IL-2. The cytotoxic T cells generated in primary cultures or in the T cell lines were specific for the HLA class I antigens of the stimulating cells. Thus, the combination of heated cells and IL-2 stimulated antigen-specific cytotoxic cells, and not merely lymphokine-activated killers. Although IL-2 production appeared to be a crucial missing component of MLCs with heated lymphocytes, the addition of IL-1, a factor known to act as a second signal for stimulating IL-2 production, did not reconstitute cytolytic activity. These results indicate that (1) heat treatment does not appreciably affect class I structure; (2) HLA class I/T cell receptor interactions are intact, resulting in responsiveness to IL-2 but not IL-1; and (3) heating creates a defect that has a minimal effect on CTL precursor activation but does disrupt a T helper cell/stimulator cell interaction critical for IL-2 production.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression

Fluoxetine is the first selective serotonin reuptake inhibitor antidepressant to be marketed in the U.S. In this double-blind trial fluoxetine was compared with imipramine and placebo among 198 outpatients with DSM-III major depression, of whom 145 completed at least 2 weeks of active treatment and were evaluated for efficacy. Significantly fewer patients in each active drug group terminated early due to lack of efficacy compared to placebo. Both imipramine and fluoxetine were significantly superior to placebo on most measures. There were no consistently significant differences between the two active drugs although a trend favored imipramine on a number of measures. Fluoxetine was generally well tolerated. Significantly more imipramine than placebo patients terminated early due to side-effects while the fluoxetine-placebo difference was not significant. The results support previous studies which suggest fluoxetine's superior side-effect profile and the approximate antidepressant equivalence of fluoxetine and TCAs.     

Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen

Summary We report a case of a male patient suffering from a severe hemorrhagic radiation proctitis which gradually ceased with hyperbaric oxygen. We discuss the mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen. This therapy is proposed as an alternative to surgical intervention for this abnormality.     

Failure to thrive and intestinal diseases in congenital disorders of glycosylation]

Congenital disorders of glycosylation type I (GDG-I) is a class of genetic multisystem disorders characterised by defective glycosylation of glycoproteins. The characteristics and mechanisms of failure to thrive and intestinal diseases present in CDG-I are anectodal. PATIENTS AND METHODS: The aim of this study was to analyse 7 CDG-I (4 CDG-Ia, 2 CDG-Ib and 1 CDG-Ix) with important digestive symptoms and failure to thrive in order to characterise the mechanisms implied. RESULTS: Four children had no skin abnormality or dysmorphia (1 CDG-Ia, 2 CDG-Ib, 1 CDG-Ix). An encephalopathy with cerebellar hypoplasia was present only in the 4 CDG-Ia. Failure to thrive and diarrhea were present during the first month of life in 6 and appeared at 5 years in one CDG-Ia associated to mild or severe hepatopathy in all patients. One CDG-Ia, 1 CDG-Ib, 1 CDG-Ix had an exsudative enteropathy. A positive steatorrhea was present in 3 patients. Five patients had an abnormal small bowel biopsy. Abnormalities were variable: moderate inflammation of the chorion without villous atrophy in 2, intra-enterocyte fat accumulation without villous atrophy in 2, and partial villous atrophy with lymphangectasia in 1. In 2 CDG-Ia the intestinal biopsy was normal. Enteral nutrition in 4 and parenteral nutrition in 2 were effective in 4 patients and 1 patient with an exsudative enteropathy respond to a free fat diet (CDG-Ix). CONCLUSION: The digestive symptoms with failure to thrive is a common feature of CDG-I and could be the first symptoms. The diagnostic should be suspected if no other cause is found. Mechanisms of the intestinal symptoms appear to be multiple such as inflammation, abnormal enterocyte lipid transport or intestinal permeability related to the abnormal glycosylation of intestinal mucosa glycoproteins.     

Fibronectin is an immunosuppressive substance associated with epithelial ovarian cancer.

BACKGROUND. Although the ascites of patients with ovarian cancer has been reported to contain immunosuppressive factors, the identity and source of this activity has not been determined. Previously, the authors showed that conditioned media from two of four epithelial ovarian cancer cell lines inhibits proliferation of mitogen-stimulated human lymphocytes. The physical characteristics of the inhibitory substance are unlike those of peptide growth factors but closely resemble those of fibronectin. METHODS AND RESULTS. In the current study, it was found that the two ovarian cancer cell lines that produce the inhibitory substance have more fibronectin on the cell surface and secrete significantly more immunoreactive fibronectin into their culture media than the other two ovarian cancer cell lines. In addition, the immunosuppressive activity was bound to a gelatin-Sepharose affinity column, known to bind fibronectin. Finally, in ascites from 20 patients with advanced epithelial ovarian cancer, fibronectin levels correlated with the ability to inhibit proliferation of lectin-stimulated lymphocytes (P < 0.001). CONCLUSIONS. Fibronectin is produced by some ovarian cancer cell lines and acts to inhibit proliferation of mitogen-stimulated lymphocytes. Additional studies are needed to clarify the role of fibronectin in ovarian cancer.     

Local fibrinolysis for superior mesenteric artery thromboembolism

A 66-year-old man with atrial fibrillation was referred soon after developing left lower limb and abdominal pain with rectal bleeding. An immediate flush aortogram showed embolic occlusion of the left distal superficial femoral artery and superior mesenteric artery (SMA), 3 cm from its ostium. Recombinant tissue plasminogen activitor (rtPA) 40 mg was selectively in stilled in the SMA in two boluses. Abdominal symptoms resolved within 48 h, and complete recanalization of the SMA was shown on angiography. Exploratory laparotomy after 72 h showed a normal small bowel and right colon, and was completed by femoropopliteal embolectomy. Six months later, the patient remained asymptomatic.