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HTLV-III Antibodies in a Patient With Mycosis Fungoides
1078
METABOLISM, ENDOCRINOLOGY AND IMMUNOLOGY
Division of Urology, Department of Surgery, UCLA School of Medicine, Harbor- UCLA Medical Center, Torrance, California
J. Clin. Endocr. Metab., 63: 1193-1198 (Nov.) 1986
Ketoconazole is a broad-spectrum antifungal agent that is known to be a potent inhibitor of human gonadal and adrenal steroidogenesis. The purpose of this study is to determine the antisteroidogenic effect of ketoconazole in the human testis. Two groups of men were studied. Group 1 consisted of 3 men with previously untreated metastatic prostatic cancer. The levels of 7 intratesticular steroids (plasma Li5 -pregnenolone, Li 5 -1 7a-hydroxypregnenolone, dehydroepiandrosterone, progesterone, testosterone, l 7a-hydroxyprogesterone and androstenedione) were measured before and after administration of oral ketoconazole. The adrenal glands in all 3 patients were suppressed with dexamethasone, which was begun 7 days before and continued during the study. After 6 doses of ketoconazole bilateral orchiectomy was performed, and the intratesticular concentration of the aforementioned 7 steroids and the intratesticular activities of 17a-hydroxy lase, 17,20-desmolase and l 7a-hydroxysteroid dehydrogenase enzymes in the b. 4 -steroidogenic pathway were determined. Group 2 consisted of 5 men with previously untreated prostatic cancer who underwent orchiectomy as primary treatment for the disease. The levels of the 7 intratesticular steroids and the 3 intratesticular enzymes were determined in all subjects. Plasma androstenedione, dehydroepiandrosterone and testosterone levels were decreased significantly during ketoconazole therapy in group 1, while there was no significant change in the other 4 plasma steroids. In the testis b. 5 -pregnenolone, Li 5 -17 a-hydroxypregnenolone and 17 a-hydroxyprogesterone were elevated significantly in all patients. Intratesticular dehydroepiandrosterone, androstenedione and testosterone were decreased significantly in only the 3 ketoconazole-treated patients. The levels of dehydroepiandrosterone, androstenedione and testosterone were not affected in group 2. There was a significant decrease in the activity of the enzymes 17a-hydroxolase and 17,20-desmolase but no change was noted in the l 7a-hydroxysteroid dehydrogenase levels in patients who received ketoconazole compared to those who did not. Based on these data it is concluded that ketoconazole inhibits testicular steroidogenesis by inhibiting 17,20-desmolase activity. This enzyme is cytochrome P-450-dependent. R. C. N. 2 figures, 1 table, 22 references
HTLV-III Antibodies in a Patient With Mycosis Fungoides
B. I.
SAHAI SRIVASTAVA,
J. P.
GETCHELL AND
H. L.
STOLL,
JR., Roswell Park Memorial Institute, Buffalo, New York and
Center for Infectious Diseases, Center for Disease Control, Atlanta, Georgia
J. Med., 17: 57-63, 1986 Among human T-lymphotropic viruses (HTL V) HTL V-I has been associated with adult T cell leukemia, HTL V-II was isolated from a T cell variant of hairy cell leukemia and HTL VIII has been identified as the etiologic agent of the acquired immunodeficiency syndrome. Although HTL V-I was isolated originally from patients believed to have an aggressive form of mycosis fungoides and the Sezary syndrome, the patients with
these malignancies generally do not have HTLV-I antibodies and in 1 study 4 of 5 with positive results showed only partial specificity of HTLV-I antibodies in an enzyme-linked immunosorbent competition assay. The authors document a patient with mycosis fungoides who had strongly positive results for HTL V-I antibodies in the enzyme-linked immunosorbent screening assay but these antibodies could not be completed out by absorption of sera with acetone-fixed MT-2 cells positive for HTLV-I, RPMI-8402 negative for HTL V or normal peripheral blood leukocytes. Furthermore, by immunofluorescence the serum did not stain fixed MT-2 cells and the peripheral blood leukocytes could not be stained with HTLV-I p-24 monoclonal antibodies before or after short-term culture. Since the patient was a prison inmate and an intravenous drug abuser with a markedly lowered T cell helper-to-suppressor ratio (he denied homosexuality), the serum was examined for HTL V-III antibodies and it was strongly positive in the enzyme-linked immunosorbent assay. Western blot analysis showed the serum to be strongly positive for HTL V-III antibodies but negative for HTLV-I antibodies. Southern blot analysis of deoxyribonucleic acid (DNA) isolated from peripheral blood leukocytes with HTL V-I and HTL V-III viral probes showed leukocytes negative for DNA sequences for both viruses. Since 1986 this 33-year-old white man had had mycosis fungoides confirmed by a skin biopsy. Although it was not possible to determine when HTL V-III infection took place owing to lack of earlier sera, it is possible that an aggressive turn of the mycosis fungoides could be associated with HTL V-III infection. Also, considering the lack of significant cross-reactivity between HTLV-III and HTLV-1 antibodies, the nature of antibodies strongly cross-reacting with HTL V-I in the enzyme-linked immunosorbent assay that could not be absorbed out by cellular or HTL V-I antigens remains uncertain. W. W. H. 3 figures, 7 references
Guidelines for the Protection of Health Care Workers in Caring for Persons Who Have Some Form of HTL VIII/LAV Infection United States Public Health Service Centers for Disease Control N. Y. State J. Med., 83: 587~591 (Nov.) 1986 The information and recommendations contained in this report have been developed with particular emphasis on health care workers and others in related occupations in which exposure might occur to blood from persons infected with human T-lymphotropic virus type 111/lymphadenopathy-associated virus (HTLV-III/LAV), the acquired immunodeficiency syndrome (AIDS) virus. The report contains detailed recommendations for precautions appropriate to prevent transmission of all blood-borne infectious diseases to people exposed in the course of their duties to blood from those who may be infected with HTLV-III/LAV virus. They emphasize that health care workers should take all possible precautions to prevent a needle puncture injury. The recommendations are based on the well documented modes of HTLV-III/LAV transmission and also incorporate a "worst case" scenario, the hepatitis B model of transmission. Because the hepatitis B virus also is blood-borne, and is hardier and more infectious than HTL V-III/LAV, recommendations that would prevent transmission of hepatitis B also will prevent transmission of AIDS. W. W. H.
METABOLISM, ENDOCRINOLOGY AND IMMUNOLOGY
Division of Urology, Department of Surgery, UCLA School of Medicine, Harbor- UCLA Medical Center, Torrance, California
J. Clin. Endocr. Metab., 63: 1193-1198 (Nov.) 1986
Ketoconazole is a broad-spectrum antifungal agent that is known to be a potent inhibitor of human gonadal and adrenal steroidogenesis. The purpose of this study is to determine the antisteroidogenic effect of ketoconazole in the human testis. Two groups of men were studied. Group 1 consisted of 3 men with previously untreated metastatic prostatic cancer. The levels of 7 intratesticular steroids (plasma Li5 -pregnenolone, Li 5 -1 7a-hydroxypregnenolone, dehydroepiandrosterone, progesterone, testosterone, l 7a-hydroxyprogesterone and androstenedione) were measured before and after administration of oral ketoconazole. The adrenal glands in all 3 patients were suppressed with dexamethasone, which was begun 7 days before and continued during the study. After 6 doses of ketoconazole bilateral orchiectomy was performed, and the intratesticular concentration of the aforementioned 7 steroids and the intratesticular activities of 17a-hydroxy lase, 17,20-desmolase and l 7a-hydroxysteroid dehydrogenase enzymes in the b. 4 -steroidogenic pathway were determined. Group 2 consisted of 5 men with previously untreated prostatic cancer who underwent orchiectomy as primary treatment for the disease. The levels of the 7 intratesticular steroids and the 3 intratesticular enzymes were determined in all subjects. Plasma androstenedione, dehydroepiandrosterone and testosterone levels were decreased significantly during ketoconazole therapy in group 1, while there was no significant change in the other 4 plasma steroids. In the testis b. 5 -pregnenolone, Li 5 -17 a-hydroxypregnenolone and 17 a-hydroxyprogesterone were elevated significantly in all patients. Intratesticular dehydroepiandrosterone, androstenedione and testosterone were decreased significantly in only the 3 ketoconazole-treated patients. The levels of dehydroepiandrosterone, androstenedione and testosterone were not affected in group 2. There was a significant decrease in the activity of the enzymes 17a-hydroxolase and 17,20-desmolase but no change was noted in the l 7a-hydroxysteroid dehydrogenase levels in patients who received ketoconazole compared to those who did not. Based on these data it is concluded that ketoconazole inhibits testicular steroidogenesis by inhibiting 17,20-desmolase activity. This enzyme is cytochrome P-450-dependent. R. C. N. 2 figures, 1 table, 22 references
HTLV-III Antibodies in a Patient With Mycosis Fungoides
B. I.
SAHAI SRIVASTAVA,
J. P.
GETCHELL AND
H. L.
STOLL,
JR., Roswell Park Memorial Institute, Buffalo, New York and
Center for Infectious Diseases, Center for Disease Control, Atlanta, Georgia
J. Med., 17: 57-63, 1986 Among human T-lymphotropic viruses (HTL V) HTL V-I has been associated with adult T cell leukemia, HTL V-II was isolated from a T cell variant of hairy cell leukemia and HTL VIII has been identified as the etiologic agent of the acquired immunodeficiency syndrome. Although HTL V-I was isolated originally from patients believed to have an aggressive form of mycosis fungoides and the Sezary syndrome, the patients with
these malignancies generally do not have HTLV-I antibodies and in 1 study 4 of 5 with positive results showed only partial specificity of HTLV-I antibodies in an enzyme-linked immunosorbent competition assay. The authors document a patient with mycosis fungoides who had strongly positive results for HTL V-I antibodies in the enzyme-linked immunosorbent screening assay but these antibodies could not be completed out by absorption of sera with acetone-fixed MT-2 cells positive for HTLV-I, RPMI-8402 negative for HTL V or normal peripheral blood leukocytes. Furthermore, by immunofluorescence the serum did not stain fixed MT-2 cells and the peripheral blood leukocytes could not be stained with HTLV-I p-24 monoclonal antibodies before or after short-term culture. Since the patient was a prison inmate and an intravenous drug abuser with a markedly lowered T cell helper-to-suppressor ratio (he denied homosexuality), the serum was examined for HTL V-III antibodies and it was strongly positive in the enzyme-linked immunosorbent assay. Western blot analysis showed the serum to be strongly positive for HTL V-III antibodies but negative for HTLV-I antibodies. Southern blot analysis of deoxyribonucleic acid (DNA) isolated from peripheral blood leukocytes with HTL V-I and HTL V-III viral probes showed leukocytes negative for DNA sequences for both viruses. Since 1986 this 33-year-old white man had had mycosis fungoides confirmed by a skin biopsy. Although it was not possible to determine when HTL V-III infection took place owing to lack of earlier sera, it is possible that an aggressive turn of the mycosis fungoides could be associated with HTL V-III infection. Also, considering the lack of significant cross-reactivity between HTLV-III and HTLV-1 antibodies, the nature of antibodies strongly cross-reacting with HTL V-I in the enzyme-linked immunosorbent assay that could not be absorbed out by cellular or HTL V-I antigens remains uncertain. W. W. H. 3 figures, 7 references
Guidelines for the Protection of Health Care Workers in Caring for Persons Who Have Some Form of HTL VIII/LAV Infection United States Public Health Service Centers for Disease Control N. Y. State J. Med., 83: 587~591 (Nov.) 1986 The information and recommendations contained in this report have been developed with particular emphasis on health care workers and others in related occupations in which exposure might occur to blood from persons infected with human T-lymphotropic virus type 111/lymphadenopathy-associated virus (HTLV-III/LAV), the acquired immunodeficiency syndrome (AIDS) virus. The report contains detailed recommendations for precautions appropriate to prevent transmission of all blood-borne infectious diseases to people exposed in the course of their duties to blood from those who may be infected with HTLV-III/LAV virus. They emphasize that health care workers should take all possible precautions to prevent a needle puncture injury. The recommendations are based on the well documented modes of HTLV-III/LAV transmission and also incorporate a "worst case" scenario, the hepatitis B model of transmission. Because the hepatitis B virus also is blood-borne, and is hardier and more infectious than HTL V-III/LAV, recommendations that would prevent transmission of hepatitis B also will prevent transmission of AIDS. W. W. H.