Fabry's Disease Mimicking an Undifferentiated Connective Tissue Disease.

We describe a patient with Fabry's disease who for many years was seen in other clinics and was thought to have an undifferentiated connective tissue disease or an incomplete form of CREST syndrome. He presented with polyarthralgias; multiple telangiectasia-like lesions in his oral mucosa, hands, and periumbilical area; mild dysphagia; Raynaud's phenomenon; bilateral leg lymphedema; renal insufficiency; and aseptic bone necrosis at both knees. The diagnosis of Fabry's disease was first suspected when ultrastructural studies on his kidney revealed the typical inclusions characteristic of glycosphingolipidosis. Diagnosis of Fabry's disease was later confirmed by finding similar inclusions in skin endothelial cells and demonstrating a low alpha-galactosidase A activity in plasma. Fabry's disease, although rare, must be considered in the differential diagnosis of patients considered to have "atypical undifferentiated connective tissue diseases," even in the absence of classic angiokeratomas.

A clonal CD4-positive T-cell line established from the blood of a patient with Sézary syndrome.

The reported inability to establish long-term T-cell lines from the blood of cutaneous T-cell lymphoma patients with circulating neoplastic T cells has hindered the development of an in vitro system to investigate Sézary syndrome. We have established a rapidly proliferating T-cell line from the peripheral blood of a patient with Sézary syndrome, which expresses a mature helper T-cell phenotype and contains cytogenetic abnormalities and T-cell receptor gene rearrangements identical to those in the patient's blood. The method of establishment and characteristics of this line are described.

Effect of heparin on the in vivo release and clearance of human platelet factor 4.

Intravenous injection of heparin (100 U/kg) into normal volunteers resulted in an increase of platelet factor 4 (PF4) level in platelet-poor plasma from a mean value of 18.1 +/- 6.6 ng/ml before the injection to 257.9 +/- 68.3 ng/ml at 5 min after injection. PF4 antigen isolated from "postheparin plasma" by adsorption on heparin-agarose and elution with 2.0 M NaCl and "authentic PF4" isolated from human platelets showed identical patterns of migration as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Material released by washed human platelets was injected intravenously into rats. The clearance of PF4 followed a biphasic exponential pattern. The half-lives (T1/2) for the fast and slow components for control rats were 1.2 and 17.1 min. Heparin significantly extended the half-life of human PF4 in rat circulation. The clearance of PF4 injected together with heparin followed a single component model with a half-life of 27.6 min. Administration of heparin to rats that had been previously injected with human platelet releasate resulted in a 30-fold increase of plasma PF4 level in their circulation. The clearance of PF4 from the circulation of these rats (T1/2 = 45 min) fitted a single component model. We propose that PF4 is originally secreted by platelets into circulation and subsequently bound reversibly to vascular sites from which it can be released back into the circulation by heparin. The fast component of PF4 clearance that is abolished by heparin may reflect binding of this protein to the endothelial cells.

An islet cell carcinoma containing glucagon and insulin. Chronic glucagon excess and glucose homeostasis.

Described here is a patient who had an islet cell carcinoma containing both glucagon (glucagonoma) and insulin (insulinoma). Complete removal of the tumor was possible. Immunoreactive glucagon (IRG) could be extracted from all parts of the tumor (approximately 50 mug./gm.) and was shown to be fully bioactive. Immunoreactive insulin (IRI) could be extracted only from one section of the tumor (approximately 30 mug./gm.). The clinical and biochemical manifestations of the disease were dermatitis, diabetes, weight loss, anemia, hypoaminoacidemia, and hyperketonemia. The diabetes was characterized by low or normal fasting blood glucose concentrations and by impaired glucose tolerance (Kg = 0.4). After complete removal of the tumor, the dermatitis cleared, the catabolic state changed into an anabolic state, blood amino acid concentrations increased, and blood ketone-body concentrations decreased. Fasting blood glucose concentrations, however, rose above 200 mg./dl., and glucose tolerance declined further (Kg = 0.15). Hourly blood sampling for 24 hours, intravenous and oral glucose tolerance tests, intravenous arginine and tolbutamide tolerance tests with serial determinations of IRG, IRI, and blood glucose were performed preoperatively and again two weeks and two months postoperatively. The results of these studies demonstrated marked abnormalities in the stimulation and suppression of glucagon and insulin release. In addition, they failed to demonstrate a glycemic effect on the chronically elevated glucagon concentrations in this patient, while identifying insulin as the dominant factor determining blood glucose homeostasis.