RESUMO
We review our experience with 27 cases of pulmonary and meningeal cryptococcosis at the University Hospital, (Kuala Lumpar, Malaysia) where this is the most common cause of adult meningitis in patients without debilitating illnesses. Of the 27 cases analysed, six presented primarily with pulmonary symptomatology which usually were mainly cough, chest pain and low grade fever. The rest presented with primarily central nervous system (CNS) symptomatology of which headaches and fever were the most consistent symptoms although a third of these patients also had pulmonary lesions noted on chest radiographs. Treatment in all cases was with amphotericin B and 5-fluorocytosine and usually till a total cumulative dose of 1.5 g of amphotericin had been reached (an average of 10 weeks). Primary pulmonary presentations, if symptomatic, were treated as per CNS cryptococcosis due to the high likelihood of CNS dissemination. Incidental pulmonary cryptococcoma found on routine chest radiographs were confirmed by biopsy under ultrasound or fluoroscopy guidance and booked for surgical resection. Death usually occurred early in patients who presented late. Once patients responded to therapy, mortality was usually avoided. The only cause of morbidity in survivors was visual impairment or blindness, and this was attributed mainly to intracranial hypertension with residual deficits determined by the measures taken to lower intracranial pressures. Our experience suggests that: (i) symptomatic patients should have combination therapy with 5-fluorocytosine and amphotericin B till at least a cumulative dose of 1.5 g amphotericin B is reached irrespective of whether they have primary CNS or pulmonary symptomatology; (ii) non-symptomatic pulmonary cryptococcoma could be treated primarily by surgical resection; (iii) visual failure or papilloedema should be treated aggressively; and (iv) prognosis is good with adequate therapy and early presentation.
Assuntos
Criptococose , Pneumopatias Fúngicas , Meningite Criptocócica , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criptococose/complicações , Criptococose/diagnóstico , Criptococose/epidemiologia , Criptococose/terapia , Quimioterapia Combinada , Feminino , Flucitosina/uso terapêutico , Seguimentos , Humanos , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/terapia , Malásia , Masculino , Meningite Criptocócica/complicações , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/terapia , Pessoa de Meia-IdadeRESUMO
A genomic fragment encoding one (HMGR1) of the three 3-hydroxy-3-methylglutaryl coenzyme A reductases (HMGRs) from Hevea brasiliensis (H.B.K.) Mull. Arg. (M.-L. Chye, C.-T. Tan, N.-H. Chua [1992] Plant Mol Biol 19: 473-484) was introduced into Nicotiana tabacum L. cv xanthi via Agrobacterium transformation to study the influence of the hmg1 gene product on plant isoprenoid biosynthesis. Transgenic plants were morphologically indistinguishable from control wild-type plants and displayed the same developmental pattern. Transgenic lines showed an increase in the level of total sterols up to 6-fold, probably because of an increased expression level of hmg1 mRNA and a corresponding increased enzymatic activity for HMGR, when compared with the level of total sterols from control lines not expressing the hmg1 transgene. In addition to the pathway end products, campesterol, sitosterol, and stigmasterol, some biosynthetic intermediates such as cycloartenol also accumulated in transgenic tissues. Most of the overproduced sterols were detected as steryl-esters and were likely to be stored in cytoplasmic lipid bodies. These data strongly support the conclusion that plant HMGR is a key limiting enzyme in phytosterol biosynthesis.
RESUMO
A novel stress-induced gene, HEVER (Hevea ethylene-responsive) from the rubber tree, Hevea brasiliensis, has been isolated and characterised. HEVER is encoded by a multigene family. The HEVER transcript is expressed at basal levels in Hevea tissues and is developmentally regulated. In addition, the HEVER transcript and protein are induced by stress treatment with salicylic acid and ethephon. Sequence analysis shows that HEVER encodes a 33 kDa protein that has significant homology to the hypothetical protein SLEXORFA-1 from the plant, Stellaria longipes, and two bacterial proteins, BAC180K-75 from Bacillus subtilis and MVRNO3-1 from Methanococcus vannielii.
Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Árvores/genética , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Dados de Sequência Molecular , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos , Árvores/metabolismoRESUMO
The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) catalyses an important step in isoprenoid biosynthesis in plants. In Hevea brasiliensis, HMGR is encoded by a small gene family comprised of three members, hmg1, hmg2 and hmg3. We have previously described hmg1 and hmg2 (Plant Mol Biol 16: 567-577, 1991). Here we report the isolation and characterization of hmg3 genomic and cDNA clones. In comparison to hmg1 which is more highly expressed in laticifers than in leaves, the level of hmg3 mRNA level is equally abundant in laticifers and leaves. In situ hybridization experiments showed that the expression of hmg3 is not cell-type specific while hmg1 is expressed predominantly in the laticifers. Primer-extension experiments using laticifer RNA showed that hmg1 is induced by ethylene while hmg3 expression remains constitutive. The hmg3 promoter, like the promoters of most housekeeping genes, lacks a TATA box. Our results suggest that hmg1 is likely to encode the enzyme involved in rubber biosynthesis while hmg3 is possibly involved in isoprenoid biosynthesis of a housekeeping nature.
Assuntos
Genes de Plantas , Hidroximetilglutaril-CoA Redutases/genética , Plantas/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Southern Blotting , Clonagem Molecular , DNA/genética , DNA/isolamento & purificação , Regulação da Expressão Gênica , Biblioteca Genômica , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Células Vegetais , Plantas/enzimologia , Regiões Promotoras Genéticas , Conformação Proteica , RNA/genética , RNA/isolamento & purificação , RNA Mensageiro/análise , RNA Mensageiro/genética , Homologia de Sequência do Ácido NucleicoAssuntos
DNA/genética , Mitocôndrias/enzimologia , Plantas/genética , ATPases Translocadoras de Prótons/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Clonagem Molecular , DNA/isolamento & purificação , Substâncias Macromoleculares , Dados de Sequência Molecular , Plantas/enzimologia , RNA/genética , RNA/isolamento & purificação , Homologia de Sequência do Ácido NucleicoRESUMO
Hevea brasiliensis is the major producer of natural rubber which is cis-1,4-polyisoprene. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) is involved in the biosynthesis of rubber and other plant products. We have used a hamster HMGR cDNA clone as a heterologous hybridization probe to isolate and characterize cDNA and genomic clones of HMGR from H. brasiliensis. Sequence analysis revealed that these clones fall into two different classes, HMGR1 and HMGR2. Comparison of the two classes shows 86% nucleotide sequence homology and 95% amino acid homology. The carboxy-termini of Hevea HMGRs are highly homologous to those of hamster, yeast and Arabidopsis HMGR. The amino-terminus of Hevea HMGR contains two potential membrane-spanning domains as in Arabidopsis HMGR while seven such domains are found in the HMGRs of other organisms. The apparent molecular mass of Hevea HMGR was estimated in western blot analysis to be 59 kDa. Northern blot analysis indicated that the HMGR1 transcript of 2.4 kb is more highly-expressed in laticifer than in leaf. Genomic Southern analysis using 3'-end cDNA probes indicates the presence of at least two HMGR genes in Hevea.