Pulmonary fibrosis and lung carcinoma: a comparative study of metaplastic epithelia in honeycombed areas of usual interstitial pneumonia with or without lung carcinoma

Usual interstitial pneumonia (UIP), or idiopathic pulmonary fibrosis, has been considered to be associated with a high risk for lung carcinoma. To investigate this well-known but still equivocal relationship, we reviewed the clinical features of UIP autopsy cases with or without lung carcinoma (n = 32 and 38, respectively), and compared the morphology and cell kinetics of metaplastic epithelia in the honeycombed areas (n = 11, each group). Thirty-two of 70 UIP autopsy cases showed lung carcinomas. Clinically, UIP with lung carcinoma showed a male predominance (P = 0.001), a higher rate of smoking history (P = 0.001) and a later onset of UIP (P = 0.02), compared with UIP without lung carcinoma. Most of the carcinomas were peripheral in origin (90%), and 65% were topographically associated with honeycombed areas or the border between honeycombing and non-fibrotic areas. Quantitative assessment of the metaplastic epithelia in the honeycombed areas revealed that squamous metaplasia, but not cuboidal cell metaplasia or bronchial cell metaplasia, occurred more frequently in UIP with lung carcinoma than in UIP without lung carcinoma (P = 0.02). There were no significant differences between the two groups with regard to the labeling indexes of Ki-67 and p53 in the metaplastic epithelia, including squamous metaplasia. The degree of atypical squamous metaplasia was not different between the two groups. The quantitative predominance of squamous metaplasia in the honeycombed areas may not be a precursor for lung carcinoma, but might reflect a constitutional susceptibility of UIP patients to develop a lung carcinoma.     

Sequential respiratory syncytial virus cytomegalovirus pneumonia following bone marrow transplantation

A 6-month-old child with familial hemophagocytic lymphohistiocytosis (FHL) experienced early sequential pneumonia due to respiratory syncytial virus (RSV) and cytomegalovirus (CMV) following bone marrow transplantation (BMT). The patient was deficient in natural killer (NK) cell activity (as found frequently in patients with FHL), and this risk factor may have played a major role in the concomitant infection by the two viral pathogens. Rapid diagnostic methods for both viruses are essential and early specific treatment may serve to ameliorate RSV- and CMV-induced lung injury in these life-threatening infections. © 1995 Wiley-Liss, Inc.     

Cytokine responses to the native and recombinant forms of the major surface glycoprotein of Pneumocystis carinii

Pneumocystis carinii is a major opportunistic pathogen and leading cause of morbidity in patients with AIDS. The major surface glycoprotein (MSG) of P. carinii, represented by a family of related proteins encoded by unique genes, is highly immunogenic and contains T cell-protective epitopes. We undertook the present study to define the CD4 T helper (Th) response by cytokine secretion to native MSG and a recombinant form of the protein, MSG-B. Spleen cells were collected from Lewis rats and restimulated with both native MSG and MSG-B. Within 24 h, the CD4 cells secreted high levels of interferon-gamma (IFN-γ) in response to both types of antigen, indicative of a Th1 response; however, after 72 h of incubation, only the native MSG stimulated secretion of IL-4 (Th2 response) from the cells. We then investigated whether the presence of IL-4 could alter the predominant Th1 phenotype by the CD4 cells in response to MSG and MSG-B. Cells cultured with native MSG and IL-4 produced low levels of IFN-γ and elevated levels of IL-4. Interestingly, cells incubated with MSG-B and IL-4 reduced production of IFN-γ, but were not stimulated to produce increased levels of IL-4. The presence of anti-IFN-γ antibody in the MSG- or MSG-B-stimulated cultures did not effect the expression of IFN-γ mRNA, suggesting that the generation of Th1 cells in response to MSG or MSG-B was not dependent on IFN-γ. We conclude that native MSG, which contains multiple forms of this antigen, and recombinant MSG elicit different cytokine responses in vitro. These data are not only important to studies of MSG, but may also be relevant to the role of MSG in the immunopathogenesis of P.carinii infection in vivo.     

运用变性高效液相色谱对肺炎克雷伯菌产ESBL进行基因分型

目的 通过运用变性高效液相色谱（DHPLC）技术对前期研究已确认产超广谱β-内酰胺酶（ESBL）的肺炎克雷伯菌临床分离株TEM型质粒进行基因分型,试图建立一种方便快捷的用于ESBL分子诊断及其流行病学监测的新方法.方法 利用PCR技术从肺炎克雷伯菌临床分离株中扩增出TEM型质粒的编码序列,扩增产物运用DHPLC技术进行分析,分析提示,异常的样本通过测序确定其基因突变的类型,最后通过比对确定其基因型.结果 共分析了101例肺炎克雷伯菌临床分离株,全部样本均扩增出TEM型质粒的编码序列,经过DHPLC分析,52例（51.4%）样本表现为单一的洗脱峰,其形态与TEM-1标准菌株的峰型相一致,测序确定它们的碱基序列亦相一致,不存在变异,为TEM-1型;49例（48.6%）样本表现为异常的洗脱峰,它们均为双峰,形态一致,但异源双链峰的高度有差异,测序结果表明它们均存在四种相同的基因突变,在NCBI网站比对后确定为TEM-116;测序结果还提示,部分样本中TEM-1和TEM-116混合存在,其比例的不同表现为DHPLC时异源双链峰高度的差异;文献检索表明,本次确定的TEM-116为一新的基因亚型,为国内首次报道.结论 DHPLC具有简便快捷、高通量和自动化的特点,重复性好,不仅可对已知突变作出即时诊断,还可发现新的基因亚型,不失为一种较好的ESBL分子诊断方法及其流行病学监测手段.     

Drift of tetM determinant in urogenital microbiocenosis containing mycoplasmas during treatment with a tetracycline antibiotic

We studied the correlation between genetic transfer of tetM determinant in Tn916 conjugative transposon by urogenital mycoplasmas (Mycoplasma hominis and Ureaplasma urealyticum) and changes in the bacterial repertoire during treatment with a tetracycline antibiotic. Basic conditions favoring the nonspecific transfer of tetM determinant into mollicute cells are determined and the allele polymorphism of tetM determinant in clinical strains of M. hominis and U. urealyticum is evaluated. The structure of tetM gene in clinical mycoplasma and ureaplasma strains is characterized by a peculiar mosaic pattern and differs from all previously described alleles of this gene. The results suggest that tetracycline resistance in mollicutes is determined by mechanisms alternative to genetic transfer of tetM determinant.     

Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response to Pseudomonas aeruginosa lung infection

Polymorphonuclear neutrophils (PMNs) are crucial for the outcome of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis. We compared PMNs and inflammatory cytokines in the lungs and blood from susceptible BALB/c and resistant C3H/HeN mice 1 and 2 days after intratracheal challenge with alginate embedded P. aeruginosa. These parameters were correlated with the quantitative bacteriology and histopathology of the lungs. After challenge, the content of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein-2 (MIP-2) was increased in the lungs and the sera and the percentage of PMNs was increased in the blood. However, 2 days after challenge the concentration of G-CSF and MIP-2 was higher in the lungs and sera of BALB/c mice. CD11b expression was higher on the PMNs of the C3H/HeN mice. The expression of CD62L on PMNs of both strains of mice was decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow and the persistent chemotactic gradient provided by MIP-2 in the lungs.     

Subtyping of Mycoplasma pneumoniae isolates based on extended genome sequencing and on expression profiles

Mycoplasma pneumoniae isolates from patients, collected over a period of 12 years in Germany, were characterized by various methods (parameters) including multilocus sequence typing, restriction fragment length polymorphisms, Western blotting with mono-specific antibodies directed against selected proteins or with polyspecific antibodies directed against the Triton X-114-soluble protein fraction, and two-dimensional gel electrophoresis. The results for 91 isolates from Germany, which were complemented with 14 isolates from the USA and 10 isolates from France, clearly showed that M. pneumoniae is a highly uniform species and that most of the isolates could be assigned to one of the two subtypes 1 and 2. The members of one subtype differ from the other with respect to the sequence of the P1 gene, the ORF6 gene, the P65 gene, and by a typical DNA restriction fragment pattern. We observed four isolates (variants), which seemed identical by the above mentioned criteria, but did not belong to either one of the two subtypes. They showed most of the subtype 2-specific features, but differed in the sequence of the P1 gene and showed a variation in the restriction fragment pattern. The appearance of subtype 1 or 2 over the last 12 years in Germany showed a dominance of subtype 1 between 1989 and 1996 and a dominance of subtype 2 between 1997 and 1998. The variant (neither subtype 1 nor subtype 2) was only detected in 1991 and 1995 but it had no epidemiological consequences.     

Mixed microbial aetiology of community-acquired pneumonia in children

Seven paediatric studies on community-acquired pneumonia with serological methods for both viruses and bacteria have been published, allowing the evaluation of concomitant multiple etiological findings. In these studies, dual viral infection has been present in 0-14%, dual bacterial infection likewise in 0-14%, and mixed viral-bacterial infection in 3-30% of the pneumonia cases. The results confirm former clinical observations that respiratory viruses often pave the way for airway-colonising bacteria. The measured frequency of multiple infections has been dependent on the available test panel, mainly on the tests used for pneumococcal aetiology. Mixed viral-bacterial infections have been especially common in young children under 2 years of age, reflecting the high frequency of respiratory syncytial virus infections and their tendency to induce bacterial co-infections. No microbe-specific viral-bacterial associations have been demonstrated. The clinical implications of mixed viral-bacterial infections, compared with viral infections alone or bacterial infections alone, have so far remained unresolved. Current guidelines recommend antibiotic therapy for all community-acquired pneumonia cases in children.     

Antibodies to pneumococcal polysaccharides in pneumonia and response to pneumococcal vaccination in young children in Papua New Guinea.

Antibodies against pneumococcal polysaccharides were measured by ELISA in Papua New Guinean children with pneumonia aged 0-14 months, in age-matched healthy Papua New Guinean controls and in healthy expatriate children living in Papua New Guinea. At 0-5 months of age, the IgG antibody titres against six of the eight polysaccharides measured were significantly lower in pneumonia patients than in both control groups. Antibody titres in 6-14-month-old Papua New Guinean controls were significantly lower than in control Papua New Guineans aged 0-5 months for five of the eight polysaccharides tested. In the 6-14-months age group the antibody titre was significantly lower in pneumonia patients than in controls for only one polysaccharide. For seven of the eight serotypes tested, antibody levels in expatriate controls did not decline with age. Antibody responses of Papua New Guinean children aged 6-18 months to a 23-valent pneumococcal vaccine were serotype dependent. Fold increases in response to the vaccine were greatest for the IgA isotype. IgG antibody responses were greater than three fold to four of the eight serotypes tested.