High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients

Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.     

Detection of HTLV-I/ATLV by using the culture of lymph node lymphocytes with adult T-cell leukemia/lymphoma

We cultured the cervical lymph node lymphocytes of a patient suffering from cutaneous T-cell lymphoma. His anti-ATLV antibody was positive by indirect immunofluorescent method (IF). ATLV was detected on these cultured cells by IF. Type C particles were observed in the cultured cells by electron microscopy. These particles were measured to be 60 to 120 nm in diameter with electron dense core, and were considered as ATLV. This case showed a possibility of detecting ATLV by culture of lymph node lymphocytes from such a patient.     

Kaposi's sarcoma in human T-cell leukemia virus type I-associated adult T-cell leukemia

Kaposi's sarcoma (KS) developed in a patient with human T-cell leukemia virus type I (HTLV-I)-associated adult T-cell leukemia who was treated with a short-term course of monoclonal antibody immunotherapy. The presentation was transient and temporally related to the underlying clinical course. The association of KS in an HTLV-I infected, but not human immunodeficiency virus (HIV)-infected, individual should alert investigators to the occurrence of KS in retroviral-associated diseases other than acquired immunodeficiency disease syndrome. Recognition of the similarities and differences between HTLV-I and HIV infections may provide insights concerning the angiopathogenesis of KS.     

Immunological studies on opportunistic infection and the development of adult T-cell leukemia.

Three patients with opportunistic infection preceding adult T-cell leukemia (ATL) are presented: a 66-year-old woman with cryptococcosis and Pneumocystis carinii pneumonia, a 46-year-old man with Pneumocystis carinii pneumonia, and a 55-year-old woman with cryptococcosis. Although, at the first examination, the first two had smoldering type ATL and the third case was an HTLV-I carrier, all three developed overt ATL 14-16 months after the onset of opportunistic infection. It is considered that there is immune suppression already present in HTLV-I carriers and in patients with smoldering ATL, and opportunistic infection is predictive of the development of ATL.     

Human T-cell leukemia/lymphoma virus: the retrovirus of adult T-cell leukemia/lymphoma

Human T (thymus-derived)-cell leukemia/lymphoma virus (HTLV) is a new retrovirus first isolated from T-cell lines from a patient with cutaneous T-cell lymphoma from the southeastern United States. Closely related viruses have since been isolated from several patients with adult T-cell leukemia and lymphoma (and some normal persons) from different areas of the world. HTLV is not a genetically transmitted endogenous virus of humans, but it rather is acquired by postzygotic infection. Natural antibodies to several purified viral proteins have been observed in infected individuals. HTLV is transmissible in vitro to human cord blood T cells, and infection results in an increased growth rate, a reduced requirement for (and often independence from) T-cell growth factor, and an abrogation of the crisis period that usually occurs a month after the establishment of normal T-cell cultures. These data suggest that HTLV is the etiologic agent in some human cases of leukemia and lymphoma.     

Familial adult T-cell leukemia/lymphoma

Clinical and laboratory data are described for two siblings who both developed adult T-cell leukemia/lymphoma resulting from infection by human T lymphotropic virus type I (HTLV-I). These findings suggest that genetic factors or virus-specific factors may determine which HTLV-I-infected individuals will develop leukemia.     

Expression of P-glycoprotein in adult T-cell leukemia cells

We have examined the expression of P-glycoprotein (P-gp) in adult T-cell leukemia (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the initial presentation. All 6 patients at the relapsed stage were P-gp positive, and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL cells was increased at the relapsed stage of one patient. P-gp of this patient was photolabeled with [3H]azidopine and the labeling was inhibited with nimodipine, vinblastine and progesterone. These results suggest that P-gp expressed in ATL cells from patients at relapsed stage has the same binding site(s) for the drugs as that in multidrug resistant cells, and is correlated with the refractory nature of the cells to chemotherapy.     

Association of HTLV-I with autoimmune thyroiditis in patients with adult T-cell leukaemia (ATL) and in HTLV-I carriers

OBJECTIVE There are few longitudinal data on the endocrine changes which occur after liver transplantation. We have therefore studied the impact of orthotopic liver transplantation (oLTX) on the hypothalamic–pituitary–gonadal hormone axis and sex steroid metabolism in men. PATIENTS AND STUDY DESIGN Ten male patients with end-stage liver failure due to alcohol induced cirrhosis (n = 2), virus-induced cirrhosis (n=5), primary biliary cirrhosis (n=1) and idiopathic cirrhosis (n=2) were included in a prospective study analysing the impact of oLTX on endocrine status. They were studied before and after oLTX with a mean follow-up of 11.6 months (range 4–23) following transplantation. MEASUREMENTS Serum levels of LH, FSH, testosterone (TE), free TE, PRL, cortisol, oestradiol (E₂) and sex hormone binding globulin (SHBG) were analysed with commercially available radioimmunoassays in all individuals before and after oLTX. Gonadotrophin releasing hormone stimulation tests were done in 5 patients before and after oLTX. Additionally, a complete urological assessment with a detailed questionnaire on sexual function was obtained from all individuals. RESULTS Prior to oLTX, endocrine status was invariably abnormal, the most prominent finding being a pathological decrease of TE in 90% and of free TE in all cases. After successful oLTX, all individuals had physiological levels of TE and of free TE which increased twofold (P<0.01) and tenfold (P<0.000 1), respectively. Additionally, serum gonadotrophin (LH/FSH) levels increased in the majority of patients, while E₂ decreased following oLTX. Endocrine changes extended beyond the hypothalamic–pituitary–gonadal hormone axis, as shown by a decrease in PRL (P<0.02) and SHBG (P<0.01) after transplantation. GnRH tests revealed normal stimulation of LH and FSH before and after oLTX in all cases. Libido, potency and frequency of sexual intercourse improved significantly after oLTX in the majority of patients. CONCLUSIONS These findings demonstrate the ability of the hypothalamic–pituitary–gonadal hormone axis and sex steroid metabolism to resume physiological function following orthotopic liver transplantation in men. Correspondingly, sexual function returns to normal in the majority of patients, despite significant alterations prior to orthotopic liver transplantation.