Dihydropteroate synthase polymorphisms in Pneumocystis carinii

Sulfa drugs are widely used in the treatment and prophylaxis of Pneumocystis carinii pneumonia. The nucleotide sequences of the sulfa target enzyme, dihydropteroate synthase (DHPS), differed substantially in human-, rat-, and mouse-derived P. carinii. Sequence variation also existed in the DHPSs from human-derived isolates. Six nucleotide changes were found in 6 human isolates; each was nonsynonymous and resulted in an amino acid change. Several of these changes were in highly conserved regions and are similar to those that cause sulfa resistance in other organisms. These data suggest that the human-derived P. carinii DHPS may be evolving under positive selective pressure from sulfa drugs.     

Granulomatous Pneumocystis carinii in AIDS patients

Seven cases of Pneumocystis carinii pneumonia with granulomatous reaction in patients infected with the human immunodeficiency virus are described. The patients were all adult men between the ages of 32 and 45 years, with different high-risk factors. Clinically, all the patients presented with a history of non-productive cough and shortness of breath. Two of the patients had a past history of pulmonary pneumocystosis. Radiologically, six patients had diffuse pulmonary infiltrates and one nodular pulmonary infiltrate. Transbronchial lung biopsies were obtained in four patients and open lung biopsies in three. All presented a predominant granulomatous reaction composed of epithelioid and multinucleated giant cells. Several other special stains to detect the presence of other microorganisms to account for the granulomatous reaction were negative.     

The lipids of Pneumocystis carinii

Dissociative identity disorder (DID; called multiple personality disorder in DSMIII-R) is a psychiatric condition in which two or more identity states recurrently take control of the person's behavior. A characteristic feature of DID is the occurrence of apparently severe amnestic symptoms. This paper is concerned with experimental research of memory function in DID and focuses on between-identity transfer of newly learned neutral material. Previous studies on this subject are reviewed and a pilot study with four subjects is described. This study is specifically concerned with the question whether self-reported asymmetries in between-identity transfer can be replicated on experimental memory tests. A secondary aim was to examine whether, in the absence of explicit transfer, implicit transfer of information would occur. The results showed that the apparent amnestic asymmetry for explicit information was substantiated in the laboratory, although at least some leakage was present between the apparently amnestic identities. No evidence was found for better performance on implicit than on explicit memory tests in the apparently amnestic identities. In the discussion, parallels between apparent amnesia in DID and state-dependent memory are drawn, and the question of simulated amnesia is addressed.     

Uptake and metabolism of L-serine by Pneumocystis carinii carinii

Serine is an important amino acid that is utilized in the biosyntheses of proteins and lipids. It is directly incorporated into the head group of phosphatidylserine, which in turn can be converted to other phospholipids. Also, it is required for the formation of long chain bases, precursors of sphingolipids. Uptake and incorporation of radiolabeled serine into both lipids and acid-precipitable material were demonstrated in Pneumocystis carinii carinii organism preparations freshly isolated from infected rat lungs. Radioactivity in proteins was about double that observed in lipids. Liquid scintillation spectrometry of metabolically radiolabeled lipids separated by thin-layer chromatography showed 53% of the total radioactivity were in phosphatidylserine, 12% in phosphatidylethanolamine, 24% in ceramides, and 11% in long chain bases and other compounds. Four long chain bases were detected by thin-layer chromatography in hydrolyzed P. carinii ceramides metabolically labeled with radioactive serine. Phytosphingosine and dihydrosphingosine were tentatively identified by their migrations on thin-layer plates. Radiolabeled ethanolamine was incorporated into P. carinii phosphatidylethanolamine, but relatively low incorporation of radiolabeled choline into phosphatidylcholine occurred. The observations made in this study indicated that P. carinii has the biosynthetic capacity to metabolize phospholipid head groups and to de novo synthesize sphingolipids. L-Cycloserine and beta-Cl-D-alanine, inhibitors of long chain base synthesis, reduced the incorporation of serine into P. carinii long chain bases and ceramides, which supported the conclusion that the pathogen synthesizes sphingolipids.     

Pneumocystis carinii pneumonia in HIV-negative immunocompromised adults

OBJECTIVES: To identify patient populations at risk of Pneumocystis carinii pneumonia (PCP) and assess the potential role of chemoprophylaxis. METHODS: Review of cases of PCP among patients admitted to a tertiary referral hospital in Sydney between January 1990 and April 1993. Cases were identified by indirect immunofluorescent antibody microscopy performed on respiratory tract specimens. RESULTS: Ninety-two episodes of PCP were diagnosed in 64 HIV-positive patients and 28 others. All HIV-negative patients had received corticosteroids combined with other immunosuppressive agents before the onset of PCP symptoms, which occurred within six months of immunosuppression. The group included nine of 150 kidney transplant recipients (6%) six of 138 liver transplant recipients (4.3%) and three of 25 patients with Wegener's granulomatosis (12%). Mortality associated with PCP in HIV-negative patients was significantly higher than in those who were HIV-positive (32% v. 8%, P < 0.005). CONCLUSION: Solid organ transplant recipients and individuals receiving treatment for Wegener's granulomatosis have a significant risk of developing PCP. Given the high mortality associated with this disease in HIV-negative patients, primary PCP chemoprophylaxis should be considered during the first six months of immunosuppression.     

Lymphocytes in host defense against Pneumocystis carinii

To determine the neuroendocrine (NE) features of thymic epithelial tumor, immunohistochemistry and electron microscopy studies were performed on eight NE tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five atypical thymomas, and 12 thymomas other than lymphocytic thymoma). Immunohistochemical studies were performed with antibodies against general markers for NE cells (synaptophysin, alpha subunit of a guanine nucleotide-binding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a broad panel of antibodies for hormonal substances. Thymic carcinoid showed synchronous diffuse immunoreactivity for the three NE markers and contained cells that were positive for a variety of hormonal products: human chorionic gonadotropin (hCG) alpha-subunit (eight of eight), hCG beta-subunit (three of eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of eight), calcitonin gene-related peptide (two of eight), and serotonin (one of eight). Conversely, although positivity for NE markers was neither synchronous nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five atypical thymomas (focal or dispersed distribution), and none of the five thymomas were positive for at least two of these NE markers. A small number of neoplastic cells were positive for hCGalpha-subunit or ACTH in three thymic carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG) were much more frequent in thymic carcinoid, but several DCG-like granules were identified in 12 of 13 non-NE tumors with or without immunoexpression of NE markers. The presence of focal or dispersed NE cells in thymic carcinoma and atypical thymoma may reflect multidirectional differentiation within the tumor, which, like cytological atypia, epithelial CD5 expression, and lack of immature T cell infiltration, may be another feature of this group at thymic tumors.     

Pneumocystis carinii and parasitic infections in transplantation

Pneumocystis carinii remains an important pathogen in organ transplantation. New therapeutic options have been developed for the prevention and treatment of P. carinii pneumonia. Parasitic infections are recognized more frequently in potential organ donors or recipients as travel and technology for transplantation extend into endemic regions. Parasites important to transplantation are largely those that can replicate in humans and that cause infection, the intensity of which is regulated by immune mechanisms in the normal host. The spectrum of parasitic infections is likely to increase with improved diagnostic methods, expansion of intestinal transplantation, and xenotransplantation.     

Pneumocystis carinii pneumonia masquerading as tuberculosis

Recent laboratory studies indicate that genetic diversity exists in human strains of Pneumocystis carinii. Structural and functional variability in infecting strains could result in differences in host-parasite interactions and the natural history of P carinii pneumonia. We report 5 unusual cases in which the clinical presentation mimicked tuberculosis. All patients were cared for at a university-based public hospital clinic in Los Angeles, Calif, during a 2-year period. These patients were chronically ill, had lost weight, and each had cavities or cystic spaces as the primary radiographic findings. None were receiving aerosol pentamidine and only one had a history of smoking. Four patients were initially treated for tuberculosis and the fifth for disseminated Mycobacterium avium complex. Pneumocystis carinii was the only pathogen identified in each case. The unusual clinical presentations delayed the diagnosis of P carinii in all 5 cases. Practitioners must be aware of the variable presentations of P carinii pneumonia.     

DNA sequences identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora

Samples of ambient air collected with three different types of spore traps in a rural location were examined for the presence of Pneumocystis carinii by screening for P. carinii-specific DNA sequences by DNA amplification. Eleven spore trap samples were analyzed by nested PCR, using oligonucleotide primers designed for the gene encoding the mitochondrial large subunit rRNA of P. carinii f. sp. carinii and P. carinii f. sp. hominis. The samples were collected over a 3-year period during the months of May to September, with a range of sampling times from 9 to 240 h. One air sample from an animal facility housing P. carinii-infected rats was also examined. P. carinii-specific amplification products were obtained from samples from each of the spore traps. The amplification products from eight air samples were cloned and sequenced. The majority of the recombinants from each of these samples had sequences identical to those of P. carinii f. sp. carinii and P. carinii f. sp. hominis, and a number of clones had single-base differences. These data suggest that sequences identical to those of P. carinii f. sp. carinii and P. carinii f. sp. hominis can be detected in samples of air collected in a rural location and that P. carinii may be a component of the air spora of rural Oxfordshire.     

Pneumocystis carinii meningoradiculitis in a patient with AIDS

Pneumocystis carinii is a common opportunistic pathogen in patients infected with the human immunodeficiency virus (HIV). Pneumocystis carinii pneumonia is common, while extrapulmonary infections with Pneumocystis carinii have been reported sparingly. The clinical features are frequently nonspecific. The detection of Pneumocystis carinii in cerebrospinal fluid (CSF) has not been reported thus far. In this report, an unusual case of Pneumocystis carinii meningoradiculitis in an HIV-infected patient who had previously received primary prophylaxis with trimethoprim-sulfamethoxazole is presented.     

Pneumocystis carinii pneumonia in HIV primary infection]

We report a case of osteoid osteoma as a cause of hip pain in a young athlete. Excision of the lesion resulted in complete relief of the symptoms.     

Genetic heterogeneity in Pneumocystis carinii: an introduction

The molecular structure of free radicals formed in gamma-irradiated orthorhombic single crystals of hydrated testosterone was investigated by Electron Nuclear Double Resonance (ENDOR) spectroscopy. Only one kind of radical was observed, which is formed by addition of hydrogen atom to oxygen atom O(3). We observed interaction of the unpaired electron, which is delocalized on the carbons C(3), C(4) and C(5), with one alpha-proton in position 4 and with four unequivalent beta-protons connected with the carbon atoms C(2) and C(6). The matrices of the hyperfine couplings and the g-factor of the radical are given.