Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two different classes of 1,3-beta-glucan synthesis inhibitors, the echinocandins and papulacandins, have anti-Pneumocystis activity in an immunosuppressed rat model for acute P. carinii pneumonia (PCP). This activity combined with potent anti-Candida activity makes the echinocandins attractive agents for treating both Pneumocystis and candidiasis in the immunocompromised patient. Natural product echinocandin L-671,329 rapidly eliminates greater than 99% of the P. carinii cysts after 4 days of treatment at a dose of 1 mg/kg twice daily while 2-3 weeks of therapy with trimethoprimsulfamethoxazole (TMP-SMZ) or pentamidine was required to achieve the same degree of cyst clearance. Effects of L-671,329, TMP-SMZ and pentamidine on the trophozoite stage of P. carinii were also explored using a P. carinii-specific DNA probe to quantitate organism load. Although L-671,329 was not as effective as the known agents against the trophozoite stage, prophylactic use of L-671,329 at a daily dose of 1 mg/kg prevented the development of cysts and trophozoites in the rat model. The foamy exudate commonly seen in lungs of animals with PCP is also absent in rats receiving L-671,329 prophylaxis. In addition to demonstrating the potential of L-671,329 as a prophylactic agent these studies also help in elucidating the life cycle of P. carinii. The observation that L-671,329 prophylaxis prevents the appearance of trophozoites, while acute therapy does not directly affect trophozoites, provides the first evidence that the cyst stage is required for trophozoite proliferation. The rapid elimination of cysts by L-671,329 in animals with acute PCP also indicates that all cysts are turning over within 4 days since it is the development of new cysts which is prevented with this compound.
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PMID:Treatment and prevention of Pneumocystis carinii pneumonia and further elucidation of the P. carinii life cycle with 1,3-beta-glucan synthesis inhibitor L-671,329. 181 47

Pneumocystis pneumonia is the most serious opportunistic infection in immunocompromised patients, particularly those with AIDS. Approved therapy is limited to pentamidine and inhibitors of folic acid synthesis, but these drugs show a high rate of adverse reactions in AIDS patients emphasizing the urgent need for additional effective therapies. Progress has, however, been hindered by lack of knowledge about this parasite's cellular characteristics. Previously we reported that beta (1,3)glucan is a major component of the Pneumocystis carinii cyst wall. This study shows that administration of aculeacin A, an inhibitor of beta (1,3)glucan biosynthesis, affects cyst wall formation, inhibits cyst maturation, and prevents severe pneumonia in steroid-treated rats. Thus this study not only demonstrates that beta (1,3)glucan is indispensable for growth of the parasite in rats, but suggests a new therapeutic strategy for human pneumocystosis.
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PMID:Yeast glucan of Pneumocystis carinii cyst wall: an excellent target for chemotherapy. 181 5

Pneumocystis carinii pneumonia is a major cause of death in AIDS patients in the United States. The presently available treatments have limited use due to a high incidence of adverse reactions. Therefore, there is an urgent need for a safer method for treatment and prevention of this disease. Recent evidence has suggested that P. carinii is related to fungi and that the wall of the cyst form contains 1,3-beta-glucan as a major constituent. Based on this, several proposed 1,3-beta-glucan synthesis inhibitors were evaluated for their ability to control P. carinii pneumonia in vivo. Compounds from two classes of 1,3-beta-glucan synthesis inhibitors, the echinocandins and papulacandins, were found to be effective against P. carinii.
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PMID:Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors. 219 75

In a effect to prevent nosocomial pneumonia and sepsis, we treated patients with severe multiple trauma with an immunomodulator--beta 1-3 polyglucose (glucan). Forty-one patients with no infection at admission were stratified using Trauma Score and included in a randomized double-blind controlled trial. They were divided into a control group (n = 20) and a glucan group (n = 21). Pneumonia occurred in 11 of 20 patients in the control group and in two of 21 recipients of glucan (p < 0.01). Sepsis occurred in seven of 20 patients in the control group and in two of 21 patients treated with glucan (p < 0.05). Considering patients with pneumonia and sepsis, a decrease was observed in nosocomial infection from 65.0 to 14.4 percent (p < 0.001). The mortality rate related to infection was 30.0 percent in patients in the control group and 4.8 percent in the group treated with glucan (p < 0.05). The general mortality rate, cerebral deaths excluded, was 42.1 percent in the control group and 23.5 percent in the glucan group.
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PMID:Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan). 821 83

We detected (1 --> 3) beta-D-glucan (beta-glucan), which is one of the major components of the cyst wall of Pneumocystis carinii, in sera obtained from patients with P. carinii pneumonia (PCP). We confirmed that beta-glucan was detectable by a beta-glucan detection kit (G test; Seikagaku Corporation) in bronchoalveolar lavage fluids (BALFs). The mean concentration of beta-glucan in BALFs obtained from specific-pathogen-free nude mice infected with P. carinii (n = 7; mean, 2,631 [range, 1,031 to 9,095] pg/ml) was significantly higher (P < 0.001) than that in uninfected, specific-pathogen-free mice (n = 7; 6.5 [range, 4.0 to 8.3] pg/ml). The mean level of beta-glucan in BALFs from PCP patients was significantly higher (P < 0.05) than that in BALFs from patients with other lung diseases (7,268 [range, 1,355 to 15,500] pg/ml [n = 4] versus 242.5 [17 to 615] pg/ml [n = 4]). In sera from six of seven patients with PCP, significant levels of beta-glucan (494.1 [8.5 to 1,135] pg/ml) were detected, while it was undetectable in patients with other lung diseases and in a control group. In five patients at follow-up, the level of beta-glucan decreased with clinical improvement. These results suggest that beta-glucan is detectable in sera from patients with PCP and it is a practical serological marker for monitoring of the disease during treatment.
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PMID:(1-->3) beta-D-glucan as a quantitative serological marker for Pneumocystis carinii pneumonia. 899 35

The clinical features of invasive deep mycosis in the critical care center was studied and the usefulness for determinations of plasma (1-->3)-beta-D-glucan, one of the major structural components of fungi, in making the diagnosis of deep mycosis was evaluated in comparison with that of blood culture and candida antigen titer using CAND-tec kit. A total of 92 febrile patients (mean age = 54.5 yr., M/F = 70/22) in our critical care center were enrolled in this study. Seventeen out of the 92 febrile patients (18.5%) were those with deep mycosis. In the deep mycosis group, there were 10 patients with fungal panperitonitis, 5 with fungaemia, one with candidal pneumonia and one with candidal empyema. A total of 52 blood samples were obtained from 17 patients with deep mycosis. Forty five out of the 52 blood samples (86.5%) were positive for serum (1-->3)-beta-D-glucan while only 10 were culture-positive. In contrast, six (15.0%) out of the 40 blood samples were obtained from 17 patients with deep mycosis were positive for candida antigen by CAND-tec kit. In the critical care center, deep mycosis is a common infection and determination of serum concentration of (1-->3)-beta-D-glucan is found to be a very useful examination in screening of deep mycosis with high sensitivity and specificity.
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PMID:[Clinical features of deep mycosis in critical care center--comparison of serological tests and cultures for mycosis]. 1048 19

Pneumocystis carinii remains a persistent cause of severe pneumonia in immune compromised patients. Recent studies indicate that P. carinii is a fungal species possessing a glucan-rich cyst wall. Pneumocandin antagonists of beta-1,3-glucan synthesis rapidly suppress infection in animal models of P. carinii pneumonia. We, therefore, sought to define the molecular mechanisms of beta-glucan cell wall assembly by P. carinii. Membrane extracts derived from freshly purified P. carinii incorporate uridine 5'-diphosphoglucose into insoluble carbohydrate, in a manner that was completely inhibited by the pneumocandin L733-560, an antagonist of Gsc-1-type beta-glucan synthetases. Using degenerative polymerase chain reaction and library screening, the P. carinii Gsc-1 catalytic subunit of beta-1,3-glucan synthetase was cloned and characterized. P. carinii gsc1 exhibited homology to phylogenetically related fungal beta-1,3-glucan synthetases, encoding a predicted 214-kDa integral membrane protein with 12 transmembrane domain structure. Immunoprecipitation of P. carinii extracts, with a synthetic peptide anti-Gsc-1 antibody, specifically yielded a protein of 219.4 kDa, which was also capable of incorporating 5'-diphosphoglucose into insoluble glucan carbohydrate. As opposed to other fungi, the expression of gsc-1 mRNA is uniquely regulated over P. carinii's life cycle, having minimal expression in trophic forms, but substantial expression in the thick-walled cystic form of the organism. These results indicate that P. carinii contains a unique catalytic subunit of beta-1,3-glucan synthetase utilized in cyst wall formation. Because synthesis of beta-1,3-glucan is absent in mammalian cells, inhibition of the P. carinii Gsc-1 represents an attractive molecular target for therapeutic exploitation.
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PMID:Cell wall assembly by Pneumocystis carinii. Evidence for a unique gsc-1 subunit mediating beta -1,3-glucan deposition. 1101 31

Drugs induce a variety of pulmonary diseases including pulmonary infiltration with eosinophilia (PIE) syndrome. We report a case of PIE syndrome which was observed after neck dissection. An 83-year-old male patient attended our clinic complaining of upper neck swelling and was diagnosed as advanced lymph node metastasis related to previously resected oral carcinoma and underwent neck dissection. Despite administration of antibiotics (piperacillin sodium, PIPC; and tosufloxacin tosilate, TFLX), fever and an elevation of the c-reactive protein (CRP) level with neutrophilia appeared, and an infiltration shadow was observed in the right lower pulmonary field. With the suspicion of pneumonia, the antibiotics were exchanged for panipenem/betamipron. However, the pulmonary infiltration spread widely, CRP increased to 12.9 mg/dl and severe eosinophilia (23%) was observed a few days after changing the antibiotics. PIE syndrome was suspected, and the patient underwent steroid mini-pulse therapy consisting of methylprednisolone sodium succinate (500 mg) and prednisolone (60 mg). After steroid therapy, the pulmonary condition largely improved. However, about 2 weeks after the start of steroid administration, a fever and a further elevation of CRP were observed with an increase of beta-D-glucan in serum. Roentgenography revealed diffuse infiltration shadows throughout the lungs, and the patient died about 3 weeks after the onset from respiratory distress. In vitro, blastogenesis of patient's peripheral blood lymphocytes was strongly enhanced by PIPC and TFLX, and they generated a large amount of interleukin-5 in the presence of PIPC or TFLX. The clinical course and laboratory examination results revealed that PIE syndrome may have been induced by PIPC and TFLX and that PIE syndrome should be suspected in treatment of carcinomas when dyspnea and pulmonary infiltration are complicated with eosinophilia.
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PMID:Pulmonary infiltration with eosinophilia (PIE) syndrome induced by antibiotics, PIPC and TFLX during cancer treatment. 1137 37

This study was conducted to evaluate clinical features at the onset of pneumonia and the usefulness of methods for diagnosing pneumonia in patients who have undergone kidney transplantation. From January 1990 to December 1998. 174 kidney transplantations were performed, and were followed by 22 cases of pneumonia. Of the 22 pneumonia patients, 16 were male and 6 were female. The median age of the 22 patients was 37.2 +/- 13.3 years. All the patients received cyclosporin A and corticosteroids. In 11 cases, the organisms were identified in the microbiology or pathology laboratory, either during life or at autopsy. Six cases were due to Pneumocystis carinii (PC), three to PC and Cytomegalovirus (CMV), one to Aspergillus, and one resulted from miliary tuberculosis. Pneumonia occurred within 4 months after kidney transplantation in most cases. The mean interval between the transplantation and the appearance of pneumonia was 77.3 +/- 34.3 days, except in the cases of Aspergillosis and miliary tuberculosis, where the intervals were 46 and 50 months, respectively. The mean interval from the appearance of symptoms to the detection of pulmonary infiltration was 3.3 +/- 4.3 days. The clinical features present when pulmonary infiltration was detected by CT were fever (91%), cough (32%), and crackles (27%). However, at this time, 55% of the cases had no symptoms other than fever. Chest radiographs were positive for pulmonary infiltration in 64% of the cases at the same time that the pulmonary infiltrates were detected by CT. Eighty percent of the cases exhibited diffuse interstitial infiltrates. Organisms were detected in 7 of 9 cases examined with bronchofiberscopy (BF). But in only one of 13 cases that did not undergo BF. Increased values of serum beta-D-glucan were detected in the early phase of three PC pneumonia cases, suggesting that beta-D-glucan is useful as a marker of PC pneumonia. The use of bronchofiberscopy was more frequent in survivors of PC pneumonia than in non-survivors, whereas the mean age was higher and coexisting CMV infections were identified more frequently in the non-survivors. We concluded that fever is important as an initial symptom of pulmonary infection. In addition, we find that CT is very useful for the detection of interstitial infiltrates, and BF is an excellent method for detecting organisms in the pneumonia patient after kidney transplantation.
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PMID:[Opportunistic pneumonia after kidney transplantation]. 1143 8

The early diagnosis of 58 patients with hematological neoplasms accompanied by severe pulmonary infections of Pneumocystis carini (Pc), or Cytomegalovirus (CMV) pneumonia was made by polymerase chain reaction (PCR) using sputum samples, and of pulmonary mycosis by measuring blood beta-glucan levels by a Limulus test. The effectiveness of early treatment for opportunistic infection based on these early stage diagnosis was evaluated and the results of pathological analyses of the lung at autopsy were analyzed. PCR identified Pc pneumonia in 7 of the total 58 patients (12.1%), and early treatment was effective in all 7 patients (100%). PCR identified CMV pneumonia in 5 patients (8.6%), and early treatment was effective in 2 of the 5 patients. The level of beta-glucan confirmed mycotic pneumonia in 9 of these 58 patients (15.5%), and early treatment was effective in 7 of these (66.7%). These findings indicate that PCR and the beta-glucan method effectively enabled clinicians to diagnose pulmonary opportunistic infection in the early stage in 21 of the 58 patients (36.2%), and that early treatment was effective in 16 of the 21 patients (76.2%). The results of the pathological analyses of the lung at autopsy were: pulmonary tumor cell infiltration in a total of 5 patients (2 with ATL, 2 with NAE and 1 with AML); infection in a total of 6 patients (2 with ML and 4 with ATL); and diffused alveolar damage in a total of 4 patients (2 with ML, 1 with ATL and 1 with AML). CMV infection was confirmed in a total of 5 patients (2 with ML and 3 with ATL), and mucormycosis in a total of 2 patients (1 with ML and 1 with ATL). Despite these findings, Pc and other fungi or bacteria were not detected. Early diagnosis and treatment by the present PCR and beta-glucan method were useful, but the underlying disease and its disease state influenced the clinical outcomes of patients with terminal pulmonary infection caused by CMV or mucor, suggesting that prevention and early diagnostic measures for these infections remain to be established.
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PMID:Early diagnosis and treatment of pulmonary opportunistic infection by using polymerase chain reaction and beta-glucan in patients with hematological neoplasms. 1150 92


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