Variation in the amount of T antigen and N-acetyllactosamine oligosaccharides in human cervical mucus secretions with the menstrual cycle

It has been hypothesized that the carbohydrate portion of mucins present in the endocervical canal plays an important role in conferring specific physicochemical properties (e.g. viscosity and hydration) to the mucus gel through the menstrual cycle. Our recent finding showing an increase in the amount of MUC5B mucin protein at midcycle has raised the question of whether the mucin O-glycan content also varies to confer specific hydrodynamic properties to secreted mucins during ovulation. Using lectins as carbohydrate probes, we have identified two common mucin oligosaccharide structures, T antigen and N-acetyllactosamine, within secretory granules in human endocervical glands during the proliferative phase of the menstrual cycle. Analysis of endocervical secretions by enzyme-linked lectin assay revealed that the amounts of T antigen and N-acetyllactosamine are maximal at midcycle. Lectin blot assay of immunoprecipitated MUC5B demonstrated that the mucin is a carrier of the T antigen and N-acetyllactosamine oligosaccharides in cervical mucus secretions. The amounts of T antigen and N-acetyllactosamine oligosaccharides on MUC5B increased during the first half of the cycle, peaked at midcycle, and dramatically dropped at the end of the cycle. The peak in MUC5B mucin protein and carbohydrate content coincides with the change in mucus character that occurs at midcycle. The role of O-glycans on mucins may be to hold water within the endocervical canal during ovulation to facilitate sperm migration.     

Cancer anorexia and cachexia

Patients with cancer cachexia experience a profound wasting of adipose tissue and lean body mass. Anorexia, although often present, is insufficient to account for tissue wasting because 1) cachexia involves massive depletion of skeletal muscle that does not occur during anorexia, 2) nutritional supplementation cannot replenish the loss of lean body mass, 3) cachexia can occur without anorexia, and 4) food intake might be normal for the lower weight of the cancer patient. Anorexia can arise from 1) decreased taste and smell of food, 2) early satiety, 3) dysfunctional hypothalamic membrane adenylate cyclase, 4) increased brain tryptophan, and 5) cytokine production. Appetite stimulants such as cyproheptadine, medroxyprogesterone acetate, and megestrol acetate do not significantly improve lean body mass. Tumor products might be more important in the development of cachexia. Cachectic patients excrete in their urine a lipid-mobilizing factor that directly stimulates lipolysis in a cyclic AMP-dependent manner and increases energy expenditure. Loss of skeletal muscle in cachexia is caused by upregulation of the ubiquitin-proteasome catabolic pathway. Cachexia-inducing tumors elaborate a sulfated glycoprotein, which directly initiates protein catabolism in skeletal muscle. The action of this proteolysis-inducing factor is attenuated by the polyunsaturated fatty acid eicosapentaenoic acid, which is also effective in preventing loss of skeletal muscle in cancer patients. Antagonists of tumor catabolic factors will provide important new agents in the treatment of cancer cachexia.     

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

Fanconi's anemia treated by allogeneic marrow transplantation

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.