UMLS:C0021051 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
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A 26-year-old Libyan woman presented with asymptomatic nodulo-ulcerative skin lesions present for 1 year. Three years prior to presentation, she had experienced a nasal discharge followed by the development of a nodule in the nasal cavity and a plaque on the hard palate. These lesions had gradually increased in size and ulcerated, resulting in perforation of the nasal septum and palate. Two years later, the patient noticed the appearance of skin lesions: a nodule on the right thumb and numerous nodulo-ulcerative lesions on the extremities. General physical examination was normal with no significant lymphadenopathy. Examination of the oral cavity revealed perforation of the distal nasal septum, with a perforated nodular plaque involving the entire palate, associated with subluxation of the upper incisors (Fig. 1a). On skin examination, multiple firm nodules and nodulo-ulcerative lesions with a central eschar and raised margins were observed. The lesions ranged in size from 0.5 to 5 cm and were distributed on the right hand and fingers, left upper arm (Fig. 1b), left calf, and right thigh. Routine laboratory investigations (liver function tests, serum calcium, electrolytes, lipid profile, urine and stool culture studies) were normal. Immunoelectrophoresis disclosed normal levels of immunoglobulins IgG, IgA, and IgM. Serologic studies for human immunodeficiency virus (HIV) and syphilis, and a tuberculin test, were all negative. A Giemsa-stained tissue smear was negative for Leishmania tropica organisms. Radiological studies disclosed a slight haziness of the maxillary sinuses with perforation of the nasal septum. A chest X-ray was normal. Histopathologic examination of biopsies taken from both the palate and from ulcerated and nonulcerated skin lesions was performed, and all showed similar findings. The biopsy of a nonulcerated skin lesion showed pseudoepitheliomatous epidermal hyperplasia with neutrophilic microabscesses (Fig. 2a). A dermal diffuse and nodular granulomatous mixed infiltrate of lymphocytes, histiocytes, giant cells, numerous eosinophils, and neutrophilic microabscesses was seen in all tissues examined. Septate hyphae were present both within giant cells and free in the dermis (Fig. 2b). The hyphae were branching at a 45 degrees angle and were positive on periodic acid-Schiff and Grocott methenamine silver stains (Fig. 2c). Fungal culture studies of material taken from an ulcerated skin lesion grew Aspergillus flavus. Blood cultures were negative for Aspergillus sp. or other microorganisms. The patient was treated with intravenous amphotericin B, but the medication was discontinued due to her intolerance to the drug. She was subsequently lost to follow-up.
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PMID:Cutaneous and paranasal aspergillosis in an immunocompetent patient. 1112 49

A debilitated 9-yr-old female red panda (Ailurus fulgens fulgens) with a recent history of corticosteroid administration displayed anorexia, depression, and diarrhea for 2 days. Blood work revealed a moderate nonregenerative anemia, leukocytosis, hypokalemia, hyperbilirubinemia, and mildly elevated alanine aminotransferase and aspartate aminotransferase. Serology was negative for occult heartworm, Toxoplasma gondii, feline leukemia virus, feline infectious peritonitis, feline immunodeficiency virus, and canine distemper virus. Electron microscopy of the feces demonstrated corona-like virus particles. The panda died 3 days after initial presentation. Histologic findings included multifocal, acute, hepatic necrosis and diffuse, necrotizing colitis. Liver and colon lesions contained intracellular, curved, spore-forming, gram-negative, silver-positive rods morphologically consistent with Clostridium piliforme. This panda most likely contracted Tyzzer's disease subsequent to having a compromised immune system after corticosteroid administration and concurrent disease.
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PMID:Tyzzer's disease in a red panda (Ailurus fulgens fulgens). 1142 5

The effect of severe protein deficiency at weaning has been studied in bone marrow, which is a primary lymphoid organ. Our experimental model of secondary immunodeficiency in Wistar rats has shown: (1) a decreased number of viable bone marrow cells (P <.0001); (2) diminished percentage of mitosis (P <.01); and (3) severe alteration in the percentage of chromosome pairs 3, 11, and 12 bearing nucleolar organizer regions (NORs) (P <.05). This last finding indicates a poor ribosomal gene activity. These alterations were reverted after the oral administration of a 20% casein diet during 5 to 9 days. However, there were no karyotype variations between the experimental groups. We conclude from these results that severe protein deficiency at weaning alters several aspects of bone marrow cell proliferation and ribosomal gene activity as determined by the number of silver stained nucleolus organizer regions.
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PMID:Cytogenetic studies in bone marrow cells from Wistar rats in protein malnutrition. 1155 33

A 33-year-old Hispanic woman with newly diagnosed human immunodeficiency virus (HIV) infection, a CD4 T-lymphocyte count of 2, viral load of 730,000 copies/mL, candidal esophagitis, seizure disorder, a history of bacterial pneumonia, and recent weight loss was admitted with tonic clonic seizure. On admission, her vital signs were: pulse of 88, respiration rate of 18, temperature of 37.7 degrees C, and blood pressure of 126/76. Her only medication was phenytoin. On examination, the patient was found to have multiple umbilicated papules on her face, as well as painful, erythematous, large, punched-out ulcers on the nose, face, trunk, and extremities of 3 months' duration (Fig. 1). The borders of the ulcers were irregular, raised, boggy, and undermined, while the base contained hemorrhagic exudate partially covered with necrotic eschar. The largest ulcer on the left mandible was 4 cm in diameter. The oral cavity was clear. Because of her subtherapeutic phenytoin level, the medication dose was adjusted, and she was empirically treated with Unasyn for presumptive bacterial infection. Chest radiograph and head computed tomography (CT) scan were within normal limits. Sputum for acid-fast bacilli (AFB) smear was negative. Serologic studies, including Histoplasma antibodies, toxoplasmosis immunoglobulin M (IgM), rapid plasma reagin (RPR), hepatitis C virus (HCV), and hepatitis B virus (HBV) antibodies were all negative. Examination of the cerebrospinal fluid was within normal limits without the presence of cryptococcal antigen. Blood and cerebrospinal cultures for bacteria, mycobacteria, and fungi were all negative. Viral culture from one of the lesions was also negative. The analysis of her complete blood count showed: white blood count, 2300/microl; hemoglobin, 8.5 g/dL; hematocrit, 25.7%; and platelets, 114,000/microl. Two days after admission, the dermatology service was asked to evaluate the patient. Although the umbilicated papules on the patient's face resembled lesions of molluscum contagiosum, other infectious processes considered in the differential diagnosis included histoplasmosis, cryptococcosis, and Penicillium marnefei. In addition, the morphology of the ulcers, particularly that on the left mandible, resembled lesions of pyoderma gangrenosum. A skin biopsy was performed on an ulcer on the chest. Histopathologic examination revealed granulomatous dermatitis with multiple budding yeast forms, predominantly within histiocytes, with few organisms residing extracellularly. Methenamine silver stain confirmed the presence of 2-4 microm fungal spores suggestive of Histoplasma capsulatum (Fig. 2). Because of the patient's deteriorating condition, intravenous amphotericin B was initiated after tissue culture was obtained. Within the first week of treatment, the skin lesions started to resolve. Histoplasma capsulatum was later isolated by culture, confirming the diagnosis. The patient was continued on amphotericin B for a total of 10 weeks, and was started on lamivudine, stavudine, and nelfinavir for her HIV infection during hospitalization. After amphotericin B therapy, the patient was placed on life-long suppressive therapy with itraconazole. Follow-up at 9 months after the initial presentation revealed no evidence of relapse of histoplasmosis.
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PMID:Disseminated histoplasmosis presenting as pyoderma gangrenosum-like lesions in a patient with acquired immunodeficiency syndrome. 1170 24

3'-Azido-3'-deoxythymidine (AZT) is the most widely used and evaluated chemotherapeutic agent for the treatment of persons with acquired immune deficiency syndrome (AIDS) and persons seropositive for human immunodeficiency virus (HIV). The National Cancer Institute nominated AZT for toxicity and carcinogenicity studies because of the impending large-scale use of AZT in the treatment of adult patients with AIDS or AIDS-related complex. alpha-Interferon A/D, which displays antiviral activity in mice, is a hybrid molecule composed of the N-terminal portion of human alpha-interferon A and the C-terminal portion of human alpha-interferon D. AZT and alpha-interferon A/D combination studies were conducted because in vitro studies of AZT and alpha-interferon have demonstrated that the combination is more effective in blocking HIV infection than either agent alone. Male and female B6C3F1 mice received AZT (approximately 98% pure) in 0.5% aqueous methylcellulose by gavage for 14 weeks or 2 years. In addition, male and female B6C3F1 mice received alpha-interferon A or alpha-interferon A/D by subcutaneous injection for 2 years, and male and female B6C3F1 mice received AZT in 0.5%% aqueous methylcellulose by gavage in combination with alpha-interferon A/D by subcutaneous injection for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, mouse bone marrow erythrocytes, and mouse peripheral blood erythrocytes. 14-WEEK AZT STUDY: Groups of 10 male and 10 female mice received AZT in 0.5% methylcellulose by gavage at doses of 0, 50, 100, 200, 800, or 2,000 mg/kg daily for 14 weeks. Additional groups of 10 male and 10 female mice received AZT in 0.5% methylcellulose by gavage at doses of 0, 100, 800, or 2,000 mg/kg daily for 14 weeks and then were held without treatment for an additional 4 weeks before necropsy. One female receiving 100 mg/kg and two females receiving 200 mg/kg died during week 1 as a result of gavage trauma; one female receiving 2,000 mg/kg also died prior to the end of the 14-week dosing period. One female receiving 2,000 mg/kg in the recovery study also died from gavage trauma during week 1. The final mean body weights of dosed mice were similar to those of the vehicle control groups at the end of the dosing period and at the end of the recovery period. Female mice receiving 200, 800, or 2,000 mg/kg gained less weight than the vehicle controls during the 14-week dosing period. Exposure to AZT was toxic to the bone marrow, resulting in significant changes in the peripheral blood (decreased hematocrit values, erythrocyte counts, and hemoglobin concentrations, and increased mean cell volume and mean cell hemoglobin) and bone marrow (erythroid hypoplasia) characteristic of a dose- and time-dependent, minimal to moderate, poorly regenerative macrocytic anemia. At the end of the 4-week recovery period, the hematology parameters had returned to normal, indicating that the hematotoxicity was reversible. 2-YEAR STUDIES: AZT Groups of 95 male and 95 female mice received AZT in 0.5% methylcellulose by gavage at daily doses of 0, 30, 60, or 120 mg/kg body weight, administered as two equal doses at least 6 hours apart, 5 days per week for 105 weeks. Each group of 95 animals was composed of a core group of 50 animals for evaluation of carcinogenic response, a group of 30 animals for evaluation of hematology and bone marrow cellularity, and a group of 15 animals from which blood was drawn for determination of plasma AZT concentrations at week 54. alpha-Interferon A/D and AZT/alpha-Interferon A/D Studies Groups of 80 male and 80 female mice received AZT in 0.5% aqueous methylcellulose by gavage at daily doses of 0, 30, 60, or 120 mg/kg body weight, given in two equal doses, 5 days per week for 105 weeks. Those groups receiving AZT also received sub-cutaneous injections of 500 or 5,000 U alpha-interferon A/D three times per week for 105 weeks. Additional groups of 80 male and 80 female mice received subcutaneous injections of the vehicle, 500 U alpha-interferon A/D, 5,000 Uutaneous injections of the vehicle, 500 U α-interferon A/D, 5,000 U α-interferon A/D, or 5,000 U α-interferon A, three times per week for 105 weeks. Each group of 80 animals was composed of a core group of 50 animals for evaluation of carcinogenic response and a group of 30 animals for evaluation of hematology and bone marrow cellularity. Because of the large number of animals involved, the 2-year studies were started in four phases and, for clarity, are presented as follows: the AZT study, the α-interferon A/D study, the AZT/500 U α-interferon A/D study, and the AZT/5,000 U α-interferon A/D study. Design of the 2-year AZT, AZT/α-Interferon A/D, and α-Interferon A/D Studies AZT Dose AZT Study AZT/500 U α-Interferon A/D Study AZT/5,000 U α-Interferon A/D Study 500 or 5,000 U α-Interferon A/D or 5,000 U α-Interferon A Study Vehicle Control 95 male and 95 female micea 80 male and 80 female miceb 80 male and 80 female miceb 80 male and 80 female miceb 30 mg/kg AZT 95 male and 95 female mice 80 male and 80 female mice 80 male and 80 female mice none 60 mg/kg AZT 95 male and 95 female mice 80 male and 80 female mice 80 male and 80 female mice none 120 mg/kg AZT 95 male and 95 female mice 80 male and 80 female mice 80 male and 80 female mice none aFor the AZT study, there were 95 male and 95 female mice; these were divided into 50 males and 50 females in the core groups, 30 males and 30 females in the clinical pathology groups (hematology and bone marrow analyses only), and 15 males and 15 females for plasma AZT concentration determinations. bFor the α-interferon A/D study and the AZT/α-interferon A/D studies, there were 80 male and 80 female mice for each study; these were divided into 50 males and 50 females in the core groups and 30 males and 30 females in the clinical pathology groups (hematology and bone marrow analyses only). Survival and Body Weights Survival and mean body weights of mice exposed to AZT, α-interferon A, α-interferon A/D, or AZT plus α-interferon A/D were generally similar to those of the vehicle control groups. Hematology and Bone Marrow Analyses All groups of male and female mice receiving AZT exhibited changes in peripheral blood and bone marrow characteristic of a dose- and time-dependent, minimal to mild, macrocytic, nonresponsive anemia. In females, these changes were evident throughout the study. In males, the macrocytic anemia had resolved by week 80 in the 30 mg/kg group; at study termination erythrocyte macrocytosis was present only in males receiving 60 or 120 mg/kg AZT or AZT plus α-interferon A/D. There were no treatment-related alterations in hematology or bone marrow parameters in groups that received only α-interferon A or A/D. Pathology Findings Incidences of squamous cell carcinoma and squamous cell papilloma or carcinoma (combined) of the vagina occurred with a positive trend and were significantly increased in groups of female mice receiving 60 or 120 mg/kg AZT alone or in combination with α-interferon A/D. Epithelial hyperplasia was observed in all dosed groups of females, and the incidence was significantly increased in the 120 mg/kg AZT group. Three renal tubule adenomas and one renal tubule carcinoma were observed in male mice receiving 120 mg/kg AZT; the combined incidence in this group exceeded the range in historical controls. A renal tubule adenoma was observed in one male receiving 60 mg AZT/kg and 500 U α-interferon A/D; how ever, none were observed in other groups. Evaluation of step sections revealed a few more renal tubule hyperplasias but no additional neoplasms. The incidence of harderian gland adenoma was increased in male mice receiving 120 mg/kg AZT and exceeded the range in historical controls. Harderian gland neoplasms were observed in other groups but did not follow a treatment-related pattern. Overall Incidences of Vaginal Neoplasms and Hyperplasia of the Vaginal Epithelium in Female Mice in the 2-Year Gavage Studies of AZT and AZT/α-Interferon A/Da Vehicle Control 30 mg AZT/kg 60 mg AZT/kg 120 mg AZT/kg AZT alone 2/197 (1&percnt;)b 1/197 0/49 (0&percnt;) 3/49 5/45 (11%&percnt;) 4/45 11/49 (22%&percnt;) 11/49 500 U α-Interferon A/D 0/49 (0%&percnt;) 0/49 0/44 (0&percnt;) 4/44 5/48 (10&percnt;) 8/48 6/48 (13&percnt;) 12/48 5,000 U α-Interferon A/D 1/50 (2&percnt;) 1/50 1/48 (2&percnt;) 4/48 5/48 (10&percnt;) 8/48 4/50 (8&percnt;) 15/50 aData are presented as number of vaginal neoplasms/number of animals microscopically examined (first line) and number of vaginal hyperplasias/number of animals microscopically examined (second line) bCombined incidences of controls from the AZT alone study and the AZT/α-interferon A/D studies; incidences in the vehicle control group from the AZT alone study are 0/50 (0%&percnt;) (neoplasms) and 0/50 (hyperplasia) Overall Incidence of Harderian Gland Neoplasms in Male Mice in the 2-Year Gavage Studies of AZT and AZT/α-Interferon A/Da Vehicle Control 30 mg AZT/kg 60 mg AZT/kg 120 mg AZT/kg AZT alone 13/200 (6%&percnt;)b 5/50 (10%&percnt;) 2/50 (4&percnt;) 10/50 (20%&percnt;) 500 U α-Interferon A/D 3/50 (6&percnt;) 3/50 (6&percnt;) 1/50 (2%&percnt;) 4/50 (8%&percnt;) 5,000 U α-Interferon A/D 3/50 (6&percnt;) 9/50 (18%&percnt;) 4/50 (8%&percnt;) 4/50 (8&percnt;) aData are presented as number of harderian gland neoplasms/number of animals necropsied bCombined incidences of controls from the AZT alone study and the AZT/α-interferon A/D studies; incidence in the vehicle control group from the AZT alone study is 3/50 (6&percnt;) Male mice had a pattern of nonneoplastic liver lesions along with silver-staining helical organisms within the liver consistent with an infection with Helicobacter hepaticus. An organism compatible with H. hepaticus was confirmed by polymerase chain reaction-restriction fragment length polymorphism-based assays. Detection of dose-related differences in neoplasm incidences in these studies was not considered to have been significantly impacted by the infection with H. hepaticus or its associated hepatitis. GENETIC TOXICOLOGY: AZT is mutagenic in vitro and in vivo. It induced gene mutations in Salmonella typhimurium strain TA102, with and without S9; no increases in mutations were noted in the other tested strains of S. typhimurium. AZT induced sister chromatid exchanges, but not chromosomal aberrations, in cultured Chinese hamster ovary cells, with and without S9. In vivo studies with male mice administered AZT by gavage showed highly significant increases in micronucleated erythrocytes in bone marrow and peripheral blood after exposure periods that ranged from 72 hours to 14 weeks. CONCLUSIONS: Under the conditions of these 2-year gavage studies there was equivocal evidence of carcinogenic activity of AZT in male mice based on increased incidences of renal tubule and harderian gland neoplasms in groups receiving AZT alone. There was clear evidence of carcinogenic activity of AZT in female mice based on increased incidences of squamous cell neoplasms of the vagina in groups that received AZT alone or in combination with α-interferon A/D. Hematotoxicity occurred in all groups that received AZT. Treatment with AZT alone and AZT in combination with α-interferon A/D resulted in increased incidences of epithelial hyperplasia of the vagina in all dosed groups of females. Synonyms: AZT; 3'-azido-2',3'-dideoxythymidine; azidodeoxythymidine; azidothymidine; 3'-azidothymidine; 3'-deoxy-3'-azidothymidine; 3'-deoxy-(8CI) (9CI); BW A509U; Compound S; ZDV; zidovudine Trade name: Retrovir®
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PMID:NTP Toxicology and Carcinogenesis Studies of AZT (CAS No. 30516-87-1) and AZT/alpha-Interferon A/D B6C3F1 Mice (Gavage Studies). 1257 4

A 6-month-old, castrated male domestic cat with progressive neurological signs of 2-3 weeks duration was necropsied. Macroscopic findings were restricted to the brain and included irregularly shaped, well-delineated but unencapsulated areas of intense black pigmentation involving the rostral portion of both cerebral hemispheres. Microscopically, numerous brown, oblong, segmented branching hyphae and conidial-like structures and extensive pyogranulomatous inflammation were identified throughout the cerebral lesion and in adjacent blood vessels. Hyphae and oval conidia were best demonstrated with either Gomori methenamine silver or periodic acid-Schiff stain. Fungal infection in the brain of this cat was unrelated to any concurrent immunodeficiency syndrome or immunosuppressive treatment. This report deals with a case of cerebral phaeohyphomycosis from which a different species of dematiaceous fungus, Cladophialophora bantiana, was isolated and identified.
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PMID:Pyogranulomatous meningoencephalitis associated with dematiaceous fungal (Cladophialophora bantiana) infection in a domestic cat. 1268 Jun 50

95 patients suffering from chronic pyelonephritis in active inflammation phase received antibacterial therapy with adjuvant drinking of silver-containing mineral water Serebryany klyuch (21 patients) or without such drinking (17 patients). Spa treatment with mineral water Serebryany klyuch in combined therapy of chronic pyelonephritis is shown to relieve clinical symptoms, decontaminate urine completely in 88.6% cases, to eliminate signs of immunodeficiency and endotoxicosis and to produce a 25.6% decrease in the recurrences for the nearest 2 years.
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PMID:[Silver-containing hydrocarbonate-calcium-magnesium mineral water in complex treatment of patients with chronic pyelonephritis]. 1294 41

The HB autoantigen, a 10-kDa DNA-binding protein recognized by autoantibodies only when bound to DNA, was identified by two-dimensional electrophoresis. Silver-stained protein spots corresponding to the antigen were excised from two-dimensional electrophoresis gels, digested with trypsin, and analyzed by matrix-assisted laser desorption/ionization-reflectron time of flight and nano-electrospray ionization-ion trap/mass spectrometry. Data base search identified the HB antigen as the barrier-to-autointegration factor, a cellular protein implicated in the cellular cycle that blocks autointegration and promotes intermolecular integration of retrovirus such as the Moloney murine leukemia and the human immunodeficiency type 1 virus. The physicochemical characteristics described for these proteins, their ability to bind double-stranded DNA but not single-stranded DNA, and their nuclear localization confirm that HB and barrier-to-autointegration factor are the same protein.
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PMID:Identification of the autoantigen HB as the barrier-to-autointegration factor. 1452 12

The usual method for detecting spirochetes in tissue sections is the silver stain; however, they are often difficult to detect due to marked background staining commonly seen with this technique. In certain clinical settings, such as neurosyphilis, congenital syphilis, and immunosuppressive conditions including human immunodeficiency virus (HIV) infection, a better method of detecting spirochetes in tissue sections is needed. We compare immunohistochemistry (IHC) with a monoclonal antibody to Treponema pallidum to silver staining in 19 biopsies from 17 patients with serologic evidence of secondary syphilis. IHC demonstrated a sensitivity of 71%, which was superior to the 41% sensitivity of the silver stain (p = 0.084). Furthermore, specificity was improved with IHC, as background artifacts were markedly reduced. Dermal spirochetes were visualized in all 12 positive cases, while epidermal organisms were seen in only eight cases. This finding lies contrary to accepted teaching that organisms are most commonly seen at the dermal epidermal junction. Of interest, perineural plasmacellular infiltrates were frequently seen in our cases (74%). Spirochetes were not seen in any of 14 control cases with similar histopathologic patterns. Although serologic studies remain the gold standard, IHC is more sensitive and specific than silver stain for detecting T. pallidum in biopsies of secondary syphilis.
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PMID:Secondary syphilis: a histologic and immunohistochemical evaluation. 1533 Sep 90

Dysfunction of the dopaminergic system accompanied by loss of dopamine in the striatum is a major feature of human immunodeficiency virus-1-associated dementia. Previous studies have shown that human immunodeficiency virus-1-associated dementia patients with a history of drug abuse have rapid neurological progression, prominent psychomotor slowing, more severe encephalitis and more severe dendritic and neuronal damage in the frontal cortex compared with human immunodeficiency virus-1-associated dementia patients without a history of drug abuse. In a previous study, we showed that methamphetamine and human immunodeficiency virus-1 protein Tat interact to produce a synergistic decline in dopamine levels in the rat striatum. The present study was carried out to understand the underlying cause for the loss of dopamine. Male Sprague-Dawley rats were administered saline, methamphetamine, Tat or Tat followed by methamphetamine 24 h later. Two and seven days later the animals were killed and tissue sections from striatum were processed for silver staining to examine terminal degeneration while sections from striatum and substantia nigra were processed for tyrosine hydroxylase immunoreactivity. Striatal tissue was also analyzed by Western blotting for tyrosine hydroxylase protein levels. Compared with controls, methamphetamine+Tat-treated animals showed extensive silver staining and loss of tyrosine hydroxylase immunoreactivity and protein levels in the ipsilateral striatum. There was no apparent loss of tyrosine hydroxylase in the substantia nigra. Markers for oxidative stress were significantly increased in striatal synaptosomes from Tat+methamphetamine group compared with controls. The results indicate that methamphetamine and Tat interact to produce an enhanced injury to dopaminergic nerve terminals in the striatum with sparing of the substantia nigra by a mechanism involving oxidative stress. These findings suggest a possible mode of interaction between methamphetamine and human immunodeficiency virus-1 infection to produce enhanced dopaminergic neurotoxicity in human immunodeficiency virus-1 infected/methamphetamine-abusing patients.
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PMID:Methamphetamine and human immunodeficiency virus protein Tat synergize to destroy dopaminergic terminals in the rat striatum. 1633 84

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