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PubMed1994

[Thoracoscopic anatomy, significance of pathologic findings in thoracoscopic open lung biopsy, and pleural mesothelioma].

To better understand diseases of the thoracic space, pathologic findings of thoracoscopic open lung biopsy are described based on thoracoscopic anatomy and pleural mesothelioma. A positive colloidal iron stain in the plasma membrane of the mesothelial cells indicates the presence of hyaluronic acid, which appeared to decrease the friction between the lung and thoracic cavity. Excess fluid in the pleural cavity was removed from specific sites in the parietal pleura with stomas. We evaluated the pathologic features of 57 video-thoracoscopic open lung biopsies. Specific diagnoses were established in 89%, and of these half were pneumothorax. Nonspecific pathologic changes were found in 11%, of which interstitial pneumonia was the most common. This procedure is useful in taking a large number of specimens for diagnosis, and to evaluate the degree and progress of fibrosis. The differential diagnosis of mesothelioma from pulmonary adenocarcinoma, reactive mesothelial hyperplasia, and sarcoma of the pleura are described. Also, to understand mutations of the p53 tumor-suppressor gene in mesothelioma, mesothelial lesions were studied with immunostaining for p53 antibody (DO-7) and with in situ hybridization for p53 mRNA. In immunohistochemical staining for DO-7, all reactive mesothelial cells were positive, and 75% of mesotheliomas including epithelial, biphasic, and sarcomatous types were positive, and 75% of mesotheliomas including epithelial, biphasic, and sarcomatous types were positive. mRNA for p53 was expressed in all reactive mesothelial cells, and in 55% of allmesotheliomas.

Biopsy↗

PubMed1995

Quantitation of transforming growth factor-beta in plasma and pulmonary epithelial lining fluid of sheep experimentally infected with maedi-visna virus.

A model of experimental infection with EV1, a lytic British isolate of maedi-visna virus (MVV), was developed. Ten Texel sheep were allocated to two groups and inoculated by the respiratory route with different inocula. Six of the animals received 10(7.2) TCID50 (tissue culture infective dose) of EV1 strain, while four sheep were sham-inoculated with identically prepared virus-free buffer solution. Experimental infection was followed for 8 weeks post-inoculation (PI), with development of precipitating antibodies to MVV developed in the MVV-inoculated animals during the first 4 weeks PI. Transforming growth factor-beta (TGF-beta) levels, in both bronchoalveolar lavage fluid supernatant and plasma samples, were measured. Concentrations of pulmonary epithelial lining fluid (PELF) TGF-beta were calculated. TGF-beta concentrations in PELF were approximately 165-fold higher than in plasma. No significant differences in the concentrations of plasma or PELF TGF-beta, either within or between groups, were observed.

Animals↗

PubMed1975

[Rapidly debilitating disease with generalized lymphadenopathy, skin involvement and interstitial pulmonary infiltration (report of three cases)].

Generalized but well-circumscribed lymphadenopathy and rash-like skin changes were observed in three men, aged 58 to 75 years. There was a reticular appearance in the chest X-ray. Dyspnoea, weakness, marked weight loss, changing but marked lymphopenia, markedly increased blood-sedimentation rate, and an always negative Tine test were present in all three. Despite antibiotics, cytostatic drugs and prednisolone the disease quickly ended fatally with high fever, general debilitation and pneumonia. Post-mortem examination revealed diffuse lymphatic hyperplasia with plasma-cell infiltration in the lymph nodes, tonsils and lymphatic tissue of the intestines, and diffuse hyperplasia of the endothelial venules, together with basophilic blast cells, eosimophilic granulocytes and reticulum cells with broad nucleoli. The spleen was normal or enlarged. Spleen, lung tissue and lymphatics, the skin in the area of the small vessels, hair follicles and sweat glands contained lymphocytes, plasma cells and eosinophilic leucocytes. The spleen, if enlarged, also had focal necroses in its periarteriolar septa. In two cases electrophoresis revealed beta-globulin poorly demarkated from gamma-globulin, doubling and increase. In the third case, IgA was markedly increased with one each monoclonal IgG1 und IgA, and corresponding shift in the chi/lambda relationship in serum. Immunohistologically, lymphocytes were made up of about 20 percent IgG-containing and about 25 percent IgA-containing cells. Lymphopenia, if present, was associated with markedly reduced blast transformation of peripheral lymphocytes to phytohaemagglutinin. The granulocytes were defective (intracellular killing of Candida albicans and Staphylococcus aureus), while the nitrobluetetrazolium test was normal. There was RBC phagocytosis in the macrophages of bone marrow and in Kupffer cells of all three cases.

Aged↗

PubMed1992

Bronchiolitis obliterans organizing pneumonia (BOOP): the cytological and immunocytological profile of bronchoalveolar lavage.

The cytological and immunocytological profile of bronchoalveolar lavage (BAL) was studied in 10 patients with idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) and compared with the data in idiopathic pulmonary fibrosis (IPF) (n = 22), chronic eosinophilic pneumonia (CEP) (n = 9), and extrinsic allergic alveolitis (EAA) (n = 24). Lymphocyte subsets were enumerated using an immunoperoxidase slide assay. The BAL pattern in BOOP patients was characterized by several features: 1) colorful cell differentials with an increase in all cell types, most markedly in lymphocytes, and more moderately in neutrophils, eosinophils and mast cells, as well as the presence of foamy macrophages and, occasionally, of plasma cells; 2) decreased CD4/CD8 ratio; 3) normal percentage of CD57+ cells; and 4) increase in activated T-cells in terms of human leucocyte antigen-DR (HLA-DR) expression, and occasionally also interleukin-2 receptor (CD25) expression. The findings were most similar to those in EAA except for the CD25 expression, which was always normal, and the CD57+ cells, which were increased in EAA. The increase in lymphocytes discriminated best between BOOP and IPF. The eosinophils were significantly higher in CEP than in BOOP with little overlap. In conclusion, BAL may be of value to distinguish between BOOP and other interstitial lung disease.

Alveolitis, Extrinsic Allergic↗

PubMed2003

[Cytomegalovirus diseases after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and related risk factors].

OBJECTIVE: To analyze the incidence of cytomegalovirus (CMV) diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and related risk factors. METHODS: The clinical data of 131 patients undergoing allo-HSCT August 1999 to July 2001 were analyzed retrospectively. RESULTS: Twenty-eight of the 131 patients developed CMV interstitial pneumonia (IP) with an incidence rate of 21.35%, 9 patients developed CMV enteritis with an incidence rate of 6.87%; in total 37 of the 131 patients developed CMV disease with the accumulative one-year incidence rate of 32.54%. Thirteen patients (35.14%)died of CMV diseases. Univariate analysis showed that accumulative incidence of CMV disease was associated with unrelated donor, II-IV degrees acute graft versus host disease (aGVHD), additional immunosuppressive therapy for GVHD, chronic graft versus host disease (cGVHD), antilymphocyte globulin (ALG)/monoclonal antibody (MoAb) administration, high dose of methylprednisolone (MP), plasma viramia-PCR (PV-PCR) positivity of patients, blood transfusion and pre-emptive treatment. Multivariate analysis showed that risk factors for CMV disease included plasma CMV-DNA positivity, immense amount of blood transfused, and additional immunosuppressive therapy for aGVHD, and pre-emptive therapy capable of turning PV-PCR positive reduced the incidence of CMV disease (RR: 3.309, 1.046, 2.242, and 0.346). CONCLUSION: CMV disease has a high morbidity and mortality in allo-HSCT patients. Patients with positive plasma CMV-DNA should receive pre-emptive therapy till their plasma CMV-DNA turns to be negative, especially in condition of severe aGVHD, immense amount of blood transfused, or additional immunosuppressive therapy.

Adolescent↗

PubMed1977

Varied pulmonary lesions with intraalveolar large lamellar bodies in an autopsy case with busulfan therapy.

Characteristic pulmonary findings in an autopsy case of a 46-year-old female who presented heavy dyspnea as her chief complaint after 3 months of busulfan therapy for chronic myeloid leukemia were reported. The pulmonary findings were classified into four types: I. alveolar proteinosis type, II. intra alveolar fibrosis type, III. interstitial fibrosis type, and IV. lipid pneumonia type with cholesterol granuloma. No other case with various findings like this case has been previously reported. It was considered that type I is the basic type, type II is a type that developed from type I, type III is a type with interstitial cell infiltration and fibrosis and type IV is a lipidrich variant of type I. A large lamellar body was first found in the granular material of type I. It is supposed that such a body consists of osmiophilic body which originated from type B alveolar epithelial cells and blood plasma.

Busulfan↗

PubMed2000

Detection of porcine interleukin-18 by sandwich ELISA and immunohistochemical staining using its monoclonal antibodies.

We describe here the development of sandwich enzyme-linked immunosorbent assay (sandwich ELISA) and immunohistochemical staining for porcine interleukin-18 (PoIL-18) and their application to detection of PoIL-18 in vivo. Ten anti-PoIL-18 monoclonal antibodies (mAb), all of which were reactive with recombinant PoIL-18 by Western blotting, were established. Four (2-C-4, 9-H-6, 11-H-5, and 12-C-12) of 10 neutralized the biologic activity of PoIL-18 to induce interferon-y (IFN-gamma) from porcine peripheral blood mononuclear cells (PBMC). Four (2-C-4, 5-F-6, 9-H-6, and 12-C-12) of 10 were shown to be useful in immunohistochemical staining and detected PoIL-18 in Kupffer cells and macrophages in hepatic focal necrosis and macrophages in interstitial pneumonia in piglets with experimental endotoxemia using formalin-fixed, paraffin-embedded sections. A sandwich ELISA was developed using mAb 7-G-8 as a capture antibody and biotinylated mAb 5-C-5 as a detection antibody. This ELISA detected PoIL-18 with a minimum detectable concentration of 20 pg/ml and did not show cross-reactivity against PoIL-1beta, IL-8, IL-12, and IFN-gamma or murine and human IL-18. Using this ELISA, PoIL-18 was detected in the plasma and the bronchoalveolar lavage fluid (BALF) of pigs experimentally infected with Actinobacillus pleuropneumoniae. The availability of this ELISA and immunohistochemical staining for PoIL-18 may contribute to a further understanding of the role of this cytokine in various porcine immune responses and diseases.

Animals↗

PubMed1994

Experimental porcine reproductive and respiratory syndrome virus infection in one-, four-, and 10-week-old pigs.

One-, 4-, and 10-week-old pigs were exposed to porcine reproductive and respiratory syndrome virus (PRRSV) to determine the effect of age on clinical signs, hematologic alterations, the onset and duration of viremia, routes of virus shedding, antibody production, and microscopic lesions produced by PRRSV isolate ATCC VR-2332. The response to PRRSV infection was similar among age groups. Fever, usually prolonged, and a marked dyspnea with cutaneous erythema when restrained for sample collection were the most consistent clinical signs. Prolonged periocular edema was unique to the 1-week-old pigs. The white blood cell count was decreased on day 4 postexposure (PE) due to decreases in neutrophils and lymphocytes. The virus was isolated from buffy coats at day 1 PE and was isolated from serum, buffy coat, or plasma at each sample collection period through the end of the trial (day 28 PE). Virus was most consistently isolated from lung, lymph node, spleen, and tonsil on day 7 PE and exclusively from lymph node, spleen, and tonsil on day 28 PE. Virus was infrequently isolated from urine and fecal and nasal swabs. Consistent microscopic changes in all age groups included interstitial pneumonia and lymph node hypertrophy and hyperplasia on days 7 and 28 PE, lymph node necrosis on day 7 PE, and subacute mononuclear myocarditis on day 28 PE. Findings presented here indicate that interstitial pneumonia, lymphoid necrosis, and mononuclear myocarditis are characteristic lesions of PRRSV isolate ATCC VR-2332 infection in 1-, 4-, and 10-week-old pigs.

Aging↗

PubMed1990

Subcellular localization of rev-gene product in visna virus-infected cells.

The 1.4-kb mRNA of visna lentivirus is expressed early during the lytic infection of sheep choroid plexus cell cultures. It encodes for visna early gene 1 (VEG1) product, since renamed rev gene product (or Rev), based on significant amino acid sequence homologies between this protein and the proteins of simian immunodeficiency virus of macaque and human immunodeficiency virus type 2. In this report, we examined the subcellular localization and time course appearance of the Rev protein in visna virus-infected cells. Immunoprecipitation assays of [35S]methionine-labeled cell lysates with antisera raised against the Rev protein revealed a polypeptide of 19 kDa (p19rev). This protein was predominant early in the viral replication cycle and accumulated preferentially in the cytoplasmic/membrane fraction of infected cells. Indirect immunofluorescence staining of infected cells confirmed the cytoplasmic location of visna Rev protein and could reveal in some stained cells a higher concentration of Rev at the cellular plasma membrane. The regulating protein, still present late in the viral lytic cycle, is packaged into mature viral particles along with the structural gag and env gene products.

Animals↗

PubMed1976

Lymphoid interstitial pneumonia.

A 19-year-old man presented with dyspnea, cough and chest pains; he also complained of nausea, anorexia and postprandial vomiting and reported a 10-kg weight loss. Generalized lymphadenopathy and some rales over both lung bases were noted and a chest radiograph showed bilateral nodular lesions. Persistent leukocytosis, thrombocytosis, proteinuria and anergy to a series of natural antigens were found. The diagnosis of lymphoid interstitial pneumonia was made from material obtained at open lung biopsy. Rapid but incomplete clearing of the lung lesions resulted from steroid therapy; the other abnormalities were corrected gradually, except for the proteinuria, which persisted. The clinical improvement and the ability to work and play have been maintained for the past 20 months.

Adult↗

PubMed2002

Bronchoalveolar lavage fluid differential cell count. How many cells should be counted?

OBJECTIVE: To investigate the number of cells to be counted in cytocentrifuged bronchoalveolar lavage (BAL) fluid preparations in order to reach a reliable enumeration of each cell type. STUDY DESIGN: A total of 136 BAL fluid samples for patients with suspected pneumonia or interstitial lung disease were investigated. Differential cell counts were performed on May-Grünwald-Giemsa-stained cytocentrifuged preparations by 2 observers, each differentiating 500 cells. Reliability for the enumeration of each cell type was expressed as phi value, as calculated in generalizability theory. RESULTS: For polymorphonuclear neutrophils (PMNs), alveolar macrophages, lymphocytes and eosinophils, an acceptable phi value of > or = .95 was reached at a count of 300 cells by 1 observer. Mast cells reached a phi value of only .674 at a count of 500 cells by 1 observer, precluding a reliable count. At a count of 500 cells by 1 observer, squamous epithelial cells, bronchial epithelial cells and plasma cells displayed phi values of .868, .903 and .816, respectively. CONCLUSION: At a count of 300 cells, PMNs, alveolar macrophages, lymphocytes and eosinophils are reliably enumerated in cytocentrifuged BAL fluid samples.

Bronchoalveolar Lavage Fluid↗

PubMed1993

Localized inflammatory pulmonary disease in subjects occupationally exposed to asbestos.

In reviewing pathology materials from patients occupationally exposed to asbestos, we identified eight patients with either localized nodules in their lung or unusual pathologic changes. The chest radiographs of six patients showed isolated parenchymal nodules thought to represent primary neoplasms. In three cases, pathologic examination of these nodules showed intraluminal fibrosis and inflammation of the distal airways, a pattern of change frequently referred to as "bronchiolitis obliterans organizing pneumonitis." In each instance, asbestos bodies were present in association with the fibroinflammatory tissue. In one case, the nodule showed a desquamative interstitial pneumonitis type pattern, and asbestos bodies were present admixed with the alveolar macrophages and occasionally within their cytoplasm. In one case, the nodule was composed of nonspecific inflammation and fibrosis with focal bronchiolitis obliterans and frequent asbestos bodies scattered throughout the area of inflammation and fibrosis, and in another case, necrotizing inflammation association with Aspergillus fungal organisms was identified. Granulomatous inflammation was the dominant pulmonary pathologic change in one patient, and the other patient's lung biopsy specimen showed a diffuse lymphocyte-plasma cell interstitial pneumonitis. The cases reported suggest that asbestos may cause localized lesions in the lung that clinically and radiographically are misinterpreted as cancer and that pathologically show inflammation and fibrosis of the distal airways. In addition, our observations suggest that asbestos may cause granulomatous inflammation, a desquamative interstitial type pneumonitis, and a lymphocytic interstitial pneumonitis type pattern. Our conclusions that asbestos may cause these pathologic changes are supported by case reports in the clinical and pathologic literature, clinicopathologic studies, and by experimental studies.

Aged↗

PubMed1994

Comparison of plasma PCR and bronchoalveolar lavage fluid culture for detection of cytomegalovirus infection in adult bone marrow transplant recipients.

Plasma PCR for human cytomegalovirus (CMV) DNA was compared with bronchoalveolar lavage (BAL) fluid culture as an indicator for disseminated CMV infection. Thirteen (32.5%) of 40 consecutive bone marrow transplant (BMT) recipients were BAL fluid culture positive for CMV on day 35 post-BMT, and 9 (69%) of the 13 had positive plasma PCRs between days 28 and 49. Of the 27 with negative BAL fluid cultures, 2 (7%) had positive plasma PCRs (P < 0.001). Plasma CMV DNA in BMT recipients is a useful clinical marker for serious infection.

Adult↗

PubMed1988

Immunoglobulin G and its function in the human respiratory tract.

Immunoglobulin G--which can be subdivided into four classes, each with different functional characteristics--is an important component of the host defense system of the respiratory tract. An excessive amount can be produced or can accumulate after airway irritation (exposure to cigarette smoke) or from immunologic stimulus of B-lymphocyte-plasma cells in types of hypersensitivity and interstitial lung diseases. Specific antibody activity can be identified in organic dust-induced hypersensitivity pneumonitis and asthma that contributes to disease pathogenesis. The availability of opsonic antimicrobial antibodies is essential for optimal function of phagocytes in uptake and containment of bacteria. With an absolute or functional deficiency of IgG, recurrent and chronic types of sinopulmonary infections occur. These extremes of IgG availability, either high levels (presumably excessive) or deficient, are discussed in this review.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Expression of viral antigens in the central nervous system of visna-infected sheep: an immunohistochemical study on experimental visna induced by virus strains of increased neurovirulence.

Icelandic sheep were infected by intracerebral inoculation with visna virus strains of increased neurovirulence. The character and severity of pathological lesions were studied in brains from four sheep that developed clinical signs 5 to 12 weeks after infection. Viral antigens were identified by immunostaining using mouse monoclonal antibodies against two core proteins and the Avidin-Biotin method of detection. The pathological lesions were in general more severe than observed following infection with the parent strain K1514. Primary demyelination, a late manifestation of infection with K1514, was detected. Thus, in addition to causing more severe pathological lesions, these neurovirulent strains apparently have an increased potential to induce primary demyelination. Viral antigens were detected in lymphocytes, plasma cells, macrophages, endothelial cells, pericytes, fibroblasts and choroidal epithelial cells. Neurons and glial cells were antigen negative. The spectrum of infected cells in the brain was similar to that observed in infections with human immunodeficiency virus. These results do not support the view that the demyelination is caused by immunological damage to infected oligodendrocytes. A perturbation of the function of oligodendrocytes through a non-productive infection could be the underlying pathogenetic mechanism and/or a non-specific demyelination due to the intense inflammatory reaction.

Animals↗

PubMed1979

Microscopic characterization of rabbit lung damage produced by Pseudomonas aeruginosa proteases.

The intratracheal administration of highly purified Pseudomonas aeruginosa proteases (ca. 10 to 100 microgram) elicited extensive, grossly observable rabbit lung damage by 3 h postinjection. Light and electron microscopic characterization of the lesions revealed: (i) progressive injury and necrosis of type I epithelial cells and capillary endothelial cells from 3 h to 1 day postinjection, and progressively increasing accumulations of erythrocytes, plasma proteins, fibrin, and released type II epithelial cell lamellar bodies in alveolar lumina during that time period; (ii) progressively increasing accumulations of macrophages, but not of polymorphonuclear leukocytes, in alveolar lumina from 3 h to 6 days postinjection; (iii) progressive hyperplasia of type II epithelial cells from 12 h to 4 days postinjection; (iv) progressive infiltration of alveolar septa by mononuclear inflammatory cells (interstitial pneumonitis) from 2 to 6 days postinjection; (v) no loss of alveolar septal connective tissue and no damage to pulmonary arterioles and venules; and (vi) almost normal alveolar structure by ca. 8 days postinjection. The study revealed that the intra-alveolar hemorrhage, the injury and necrosis of alveolar septal cells, and the infiltration by mononuclear cells that have been reported to occur during human pseudomonas pneumonia can also be elicited by the experimental administration of pseudomonas proteases. Thus, the results support the idea that in vivo production and activity of P. aeruginosa proteases is important, at least in part, in eliciting the lung damage characteristic of pseudomonas pneumonia.

Animals↗

PubMedDate not supplied

Maedi-visna virus and its relationship to human immunodeficiency virus.

Maedi-visna is a slow virus infection of sheep leading to a progressing lymphoproliferative disease which is invariably fatal. It affects multiple organs, but primarily the lungs where it causes interstitial pneumonia (maedi). Infection of the central nervous system was commonly observed in Icelandic sheep (visna), infection of mammary glands (hard udder) in sheep in Europe and the USA, and infection of the joints in sheep in the USA. The name ovine progressive pneumonia (OPP) is commonly used in the USA and ovine lentivirus (OvLV) infection is also a name used for maedi-visna. A related infection of goats, caprine arthritis-encephalitis (CAE), is common in Europe and the USA. The natural transmission of maedi-visna is mostly by the respiratory route, but also to newborn lambs by colostrum and milk. Intrauterine transmission seems to be rare and venereal transmission is not well documented. Macrophages are the major target cells of maedi-visna virus (MVV), but viral replication is greatly restricted in the animal host, apparently due to a posttranscriptional block. The low-grade viral production in infected tissues can explain the slow course of the disease in sheep. The lesions in maedi-visna consist of infiltrates of lymphocytes, plasma cells, and macrophages, and are detectable shortly after experimental transmission. Several studies indicate that the lesions are immune mediated and that cytotoxic T-lymphocytes may be important effector cells. The persistence of the MVV infection is explained by a reservoir of latently infected blood and bone marrow monocytes, which migrate into the target organs and mature into macrophages with proviral DNA transcription, but limited replication of virus. The MVV particles are morphologically similar to those of other retroviruses and the mode of replication follows the same general pattern. The genome organization and gene regulation resembles that of other lentiviruses. In addition to gag, pol and env, MVV has three auxiliary genes (tat, rev and vif), which seem to have similar functions as in other lentiviruses, with a possible exception of the tat gene. A determination of the 9200 nucleotide sequence of the MVV genome shows a close relationship to CAE virus, but limited sequence homology with other lentiviruses, and only in certain conserved domains of the reverse transcriptase and possibly in the surface protein. MVV infection in sheep and HIV-1 infection in humans have a number of features in common such as a long preclinical period following transmission, and a slow development of multiorgan disease with fatal outcome. A brief early acute phase, which is terminated by the immune response, is also an interesting common feature. Like HIV-1, MVV is macrophage tropic and the early stages of the HIV-1 infection which affect the central nervous system and the lungs are in many ways comparable to maedi-visna. In contrast to HIV-1, MVV does not infect T-lymphocytes and does not cause T-cell depletion and immunodeficiency. This is responsible for the difference in the late stages of the HIV-1 and MVV infections and the final clinical outcome. Despite limited sequence homology, certain proteins of MVV and HIV-1 show structural and functional similarities. Studies of MVV may therefore help in the search for new drugs against lentiviruses, including HIV-1.

Animals↗

PubMed1989

Testicular lesions in rams infected by maedi/visna virus.

Pathological lesions were observed in the testicles of 5 out of 7 rams found to be infected by maedi virus serologically and by histopathological examination of the lungs. The interstitium of the testicles was infiltrated with lymphocytes, histiocytes and plasma cells. The infiltration was mainly perivascular and of varying severity, and was accompanied by fibrosis. The seminiferous tubules neighbouring the severely affected parts were atrophied and, as a result, in circumscribed areas of the testicles disturbances of spermatogenesis were observed. The epididymides were devoid of pathological changes. Studies are in progress to determine whether the testicular lesions are actually caused by maedi/visna virus. Transmission of the virus with infected rams' semen is possible.

Animals↗