Cytolytic CD8+ T lymphocytes are the main cell type involved in the fatal lymphoproliferative-accelerated phase of the Chediak-Higashi syndrome (CHS). To generate a cellular tool to study the defects ...of this T cell subset in vitro, we have used Herpesvirus saimiri, a lymphotropic virus that transforms human T lymphocytes into extended growth and in addition, endows them with natural killer (NK) features. Transformed CHS CD8+ T cells were generated and characterized in comparison with healthy controls. The results showed that transformed CHS T cells maintained the defects described in primary CHS lymphocytes, such as giant secretory lysosomes and impaired NK and T cell receptor/CD3-induced, perforin-mediated cytolytic activity which, however, could be restored after extended culture in the presence of interleukin-2 (IL-2). Upon activation with phorbol ester plus calcium ionophore or upon extended culture with IL-2, transformed CHS T cells showed normal, perforin-independent plasma membrane CD178/CD95L/FasL-mediated cytolytic activity but negligible secretion of microvesicle-bound CD95L. Transformed (and primary) CHS T cells were otherwise normal for cytolysis-independent activation functions, such as proliferation, surface expression of several activation markers including major histocompatibility complex class II, and cytokine or surface activation-marker induction. Therefore, the CHS protein CHS1/LYST (for lysosomal traffic regulator) can be dispensable for certain NK and T cell cytolytic activities of activated CHS CD8+ T lymphocytes, but it seems to be required for microvesicle secretion of CD95L. We conclude that transformed CHS T cells may be useful as a tool to study in vitro the relative role of CHS1/LYST in NK and T lymphocyte cytolysis and antigen presentation.
A case is reported of a patient with hypoglycemia episodes secondary to a large sized malignant insulinoma with metastases to the liver. For the control of hypoglycemic episodes, both diet and ...octreotide were initially used but the response obtained was poor. Later, oral diazoxide was used and a good initial response was obtained but treatment was stopped due to severe adverse effects. To obtain a decrease in the tumoral size both adrimaycin and streptozotocin were administered but results were unsuccessful. Finally, embolization of the right hepatic artery was performed and no further hypoglycemic episodes occurred during the following 14 months. We conclude that selective hepatic embolization is a good therapeutic option to control hypoglycemic episodes in malignant insulinoma with metastases to the liver when other therapeutic options have proved unsuccessful.
To analyse risk factors for amputation in diabetic foot ulcers.
We have studied 152 diabetic patients (in 14 food ulcers treatment was amputation) who were attendance between January 1996 and June ...1998 in the diabetic foot Unit. Subjects with gangrene were excluded.
Risk factors for amputation were: previous history of amputation (odds ratio 3.7; 1.0113.7), proliferative retinopathy, osteomielitis, and independently clinical signs of peripheral vasculopathy (7.1; 1.88-27.2) and severe infection (14.4; 2.92-71.2).
Diabetic subjects with foot ulcers and previous history of amputation, proliferative retinopathy, osteomielitis, clinical signs of peripheral vasculopathy and/or severe infection were a high risk group for amputation and in this group aggressive therapeutical and preventive approaches should be done in order to prevent amputation.
Forty-three cases of intermittent acute porphyria (IAP) in 19 families grouped along the riverside of the Segura River in the region of Murcia (1,000,000) were collected. Twenty nine cases had the ...typical clinical manifestations of the disease, 22 with analytic confirmation. Fourteen asymptomatic disease carriers were detected by determination of the uro-synthetase activity. Out of 22 hospitalized patients, 18 presented neurologic manifestations, 13 with polyneuropathy mainly of the proximal type. In some cases weakness extended distally. In the few cases in whom the polyneuropathy was initially distal there was never a Landry type of ascent. The most severe cases of polyneuropathy left characteristic sequelae in the hands.