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PubMed1998

Structural responses of pulmonary intravascular macrophages in lentivirus-infected and/or recombinant ovine interferon-tau-treated lambs.

Ovine lentivirus (OvLV), a retrovirus, infects and disseminates to various tissue organs via monocytes. The differentiation of infected monocytes into macrophages is a prerequisite for viral replication, and the presence of infected macrophages in tissue organs induces chronic immunopathology such as lymphoid interstitial pneumonia. The pulmonary intravascular macrophage (PIM) is a recently identified mononuclear phagocyte in domestic animal species, including sheep. Recombinant ovine interferon-tau (roIFN-tau), a type I IFN originally named as the ovine trophoblast protein, has potent antiviral activity against OvLV and human immunodeficiency virus and prevents the development of OvLV-associated lung pathology. We investigated and compared the structural features of PIMs in OvLV-infected and/or roIFN-tau-treated 1-month-old lambs using transmission electron microscopy. The PIMs' numerical counts were performed in toluidine blue-stained sections of Epoxy-embedded lung tissues. A reduction in the number of PIMs was observed with OvLV infection and/or roIFN-tau treatment of lambs as compared to the control group (P < or = 0.05). The majority of the PIMs in OvLV-infected and/or roIFN-tau-treated groups were devoid of their surface coat. The PIMs of OvLV-infected lambs exhibited signs of biosynthetic activation such as expanded rough endoplasmic reticulum, prominent Golgi complexes, and accumulation of secretory vesicles. A few PIMs contained OvLV-like structures. In roIFN-tau-treated OvLV-infected lambs, the lymphocytes had ruffled plasma membranes and were in intimate contact with the PIMs, as is observed during cytotoxic cell-mediated killing of target cells. Most of the PIMs in roIFN-tau-treated OvLV-infected lambs appeared smaller in size. Ovine lentivirus and roIFN-tau, individually or in combination, alter the integrity of the surface coat of PIMs and cause their disappearance from the lungs. Ovine lentivirus infection induces morphological changes that correlate with cytotoxic cell behavior between lymphocytes and PIMs in roIFN-tau-treated or placebo-treated lambs. The loss of PIMs, probably infected with OvLV, either through direct killing by roIFN-tau or indirectly by roIFN-tau-activated cytotoxic T lymphocytes may represent different aspects of therapeutic actions of this cytokine.

Animals↗

PubMedDate not supplied

Lentiviral diseases of sheep and goats: chronic pneumonia leukoencephalomyelitis and arthritis.

This review describes the pathogenesis of a slowly progressive disease complex caused by naturally occurring nononcogenic retroviruses in sheep and goats. In nature, infections are usually clinically silent, but disease may manifest itself after prolonged incubation periods. Clinically, this is seen as dyspnea, progressive paralysis, and/or progressive arthritis. In all organs the basic lesion is inflammatory with infiltration and proliferation of lymphocytes, plasma cells, and macrophages. Other organ-specific pathologic changes such as primary demyelination in the central nervous system and degeneration of cartilaginous structures in joints accompany inflammation. The viruses infect tissue-specific macrophage populations in vivo. Viral replication in these cells is restricted to minimal levels but continues indefinitely in the animal as a result of either failure to induce specific neutralizing antibodies or antigenic drift when neutralizing antibodies develop. Consistent low-grade viral replication sets the pace for disease by providing continuous antigenic stimulation for the inflammatory cellular immune response or antibodies that localize in the target tissues. These cells and immune complexes may have adverse effects on indigenous cell populations.

Animals↗

PubMed1991

Cellular basis for the elevated gallium-67 computed lung index in a rheumatoid lung patient.

A patient with high levels of serum rheumatoid factor and an open lung biopsy which showed high-grade interstitial pneumonia with large numbers of lymphocytes and plasmocytes had intense gallium uptake in the lungs. Lymphocytes and/or plasmocytes might be responsible for the gallium uptake even though neutrophils are usually credited with high-level uptake. Differential cell counts demonstrated plasmocyte and lymphocyte preponderance, but neutrophil paucity. In vitro cell cultures of purified neutrophils, monocytes, leukemic plasmocytes, and resting and stimulated lymphocytes with 67Ga showed that plasmocytes take up comparatively low levels of 67Ga, but that activated lymphocytes take up levels that approach neutrophils. It is probable that both rheumatoid lung plasmocytes and activated lymphocytes are responsible for the pulmonary 67Ga concentration in this patient.

Aged↗

PubMed1986

Pulmonary and systemic consequences of localized acid aspiration.

Acid aspiration may recruit a generalized inflammatory reaction that can potentiate the local injury. After surgical isolation of bronchi in a group of 15 dogs, 1 milliliter per kilogram of 0.37 normal hydrochloric acid was instilled into either side. After five minutes, platelet and white blood cell counts fell to 10,000 and 1,000 per cubic millimeter (p less than 0.05). Platelet aggregates were noted in blood smears. 111Indium-platelet activity doubled over both the aspirated and nonaspirated lung (p less than 0.05). Physiologic dead space rose from 18 to 67 per cent and to 46 per cent in the aspirated and nonaspirated lung (p less than 0.05). Physiologic shunt increased from 12 to 47 per cent and to 43 per cent (p less than 0.05) on the two sides. Plasma thromboxane B2 levels at 30 minutes rose from 0.28 to 0.93 nanograms per milliliter (p less than 0.05). Edema fluid from the aspirated lung had thromboxane B2 values of 2.87 nanograms per milliliter, indicating pulmonary synthesis. Within five minutes of aspiration, systemic effects were prominent; mean arterial pressure fell from 114 to 46 milliliters of mercury (p less than 0.05), and the cardiac index fell 24 per cent from 106 to 81 milliliters per kilogram per minute (p less than 0.05) along with an 18 per cent decrease in contractility of a rat papillary muscle bathed in plasma from the aspirated dog. Mean pulmonary arterial pressure rose from 12 to 18 millimeters of mercury (p less than 0.05). Despite fluid infusion at 36 milliliters per kilogram per hour to keep wedge pressure constant at 5.5 millimeters of mercury, and sampling of one-third the blood volume, hemoglobin concentration rose 0.9 grams per cent (p less than 0.05) indicating increased microvascular permeability. At autopsy, the aspirated and nonaspirated lung were indistinguishable with congestion, interstitial hemorrhage, and white blood cell infiltrates. Systemic organs showed vascular congestion and edema. These data demonstrate that local aspiration leads to generalized inflammatory sequelae with cardiopulmonary failure.

Animals↗

PubMed1981

Ovine progressive pneumonia: experimental intrathoracic, intracerebral, and intra-articular infections.

Three groups of 4 lambs each were experimentally infected with an isolate of progressive pneumonia virus (PPV) by intracerebral, intra-articular, or intrathoracic routes of inoculation. An additional control group was sham-inoculated by all 3 routes with identically prepared, noninfected inoculum. Sheep were killed 12 to 42 days after inoculation. A mild generalized leptomeningitis was found in 2 of the 4 lambs inoculated intracerebrally. A severe, proliferative synovitis with massive infiltration of lymphocytes and plasma cells was found in the 4 lambs inoculated intraarticularly. Germinal center formation was found in the synovial membrane 42 days after inoculation. Appreciable differences in lung morphologic features were not observed among the 4 groups. The PPV was isolated from virus-inoculated sheep from the choroid plexus, synovium, and lungs from inoculated and noninoculated sites. Nine of the 12 virus-inoculated lambs developed serum antibody to PPV, and specific antibodies were found in the synovial fluid of virus-inoculated joints. Virus was not isolated, lesions were not found, and serum antibody was not demonstrated in sham-inoculated sheep.

Animals↗

PubMed1991

Surgical pathology of the lung in Wegener's granulomatosis. Review of 87 open lung biopsies from 67 patients.

We report the pulmonary pathologic features in 87 open lung biopsies from 67 patients with Wegener's granulomatosis (WG) who were treated at a single institution from 1968 to 1990. At the time of open lung biopsy, 48 patients (72%) had classical WG with renal involvement; 19 (28%) had limited WG without renal involvement. The pathologic features were divided into major and minor manifestations. In the 82 specimens demonstrating no infectious organism, the three major pathologic manifestations of classical WG observed were also useful diagnostic criteria and included: (a) parenchymal necrosis, (b) vasculitis, and (c) granulomatous inflammation accompanied by an inflammatory infiltrate composed of a mixture of neutrophils, lymphocytes, plasma cells, histiocytes, and eosinophils. Parenchymal necrosis was found in 84% of biopsy specimens either as neutrophilic microabscesses (65% of specimens) or as large (67%) or small (69%) areas of geographic necrosis. Areas of geographic necrosis were usually surrounded by palisading histiocytes and giant cells. Additional granulomatous lesions consisted of microabscesses surrounded by giant cells (69%), poorly formed granulomas (59%), and scattered giant cells (79%). Sarcoid-like granulomas were uncommon (4%), and in only one specimen (1%) appeared within an inflammatory lesion of WG. Vascular changes were identified in 94% of biopsy specimens. Vascular inflammation was classified as chronic (37% arterial, 64% venous), acute (37% arterial, 29% venous), non-necrotizing granulomatous (22% arterial, 9% venous), and necrotizing granulomatous (22% arterial, 10% venous). Fibrinoid necrosis was relatively uncommon (11% arterial, 6% venous). Cicatricial changes were found in arteries in 41% of biopsy specimens and in veins in 16%. Capillaritis was present in 31% of specimens. Minor pathologic lesions were commonly observed in biopsy specimens associated with classical WG lesions, but they were usually inconspicuous and not useful diagnostic criteria. These included interstitial fibrosis (26%), alveolar hemorrhage (49%), tissue eosinophils (100%), organizing intraluminal fibrosis (70%), endogenous lipoid pneumonia (59%), lymphoid aggregates (37%), and a variety of bronchial/bronchiolar lesions including acute and chronic bronchiolitis (51% and 64%), follicular bronchiolitis (28%), and bronchiolitis obliterans (31%). These minor lesions were often found at the periphery of typical nodules of WG. However, in 15 specimens (18%) a minor pathologic feature represented the dominant or major finding: pulmonary fibrosis (six specimens, 7%), diffuse pulmonary hemorrhage (six specimens, 7%), lipoid pneumonia (one specimen, 1%), acute bronchopneumonia (one specimen, 1%), and chronic bronchiolitis, bronchiolitic obliterans with organizing pneumonia (BOOP), and bronchocentric granulomatosis (one specimen, 1%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMedDate not supplied

Lung cyst formation in lymphocytic interstitial pneumonia: CT features.

OBJECTIVE: We performed this study to identify and characterize the CT findings of lymphocytic interstitial pneumonia (LIP). MATERIALS AND METHODS: The CT findings of two patients with LIP were reviewed and correlated with their histologic specimens. RESULTS: Chest CT of the two patients showed areas of increased attenuation in both lung fields which were associated with nodular and cystic lesions surrounding the peribronchovascular bundles. The most characteristic abnormality identified on CT was the presence of multiple cysts throughout both lungs. Macroscopic findings of lung biopsy specimens included multiple nodular and cystic lesions. CONCLUSION: This description of multiple pulmonary cysts formation in LIP is new.

Adult↗

PubMed1999

The role of busulfan in bone marrow transplantation.

High-dose busulfan is an important component in many conditioning protocols for hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) in both adults and children. During the past 12y several studies have reported the wide inter-individual variability in busulfan disposition. Age, disease status, hepatic function, circadian rhythmicity, drug interactions and bioavailability, were identified as factors contributing to the high inter-individual variability found in busulfan disposition. Traditionally, a standard busulfan dose of 4mg/kg/d for four days is used in most BMT/HSCT protocols. Many investigations have pointed out the pharmacodynamic relationship between a high busulfan systemic exposure and the occurrence of BMT related toxicity including hepatic veno-occlusive disease (VOD), interstitial pneumonia and alopecia in adult patients. However, studies in young patients have shown a high rate of graft failure and subsequently relapse which most probably is due to the low systemic exposure despite the standard dose schedule. In children and infants VOD was not observed with the standard doses. Increasing interest for the drug and new modification strategies for children led to higher rate of VOD and CNS toxicity when busulfan was administered according to the body surface area. More pharmacodynamic studies are required to establish the relation between the systemic exposure to busulfan and the therapeutic efficacy, especially in young children undergoing BMT or HSCT. In the present time an accurate and effective busulfan plasma level monitoring combined with dose adjustment based on the known pharmacological parameters may improve the clinical outcome for patients undergoing BMT.

Adult↗

PubMed1984

Lymphoid interstitial pneumonia associated with depressed cellular immunity and polyclonal gammopathy.

This report describes a case of lymphoid interstitial pneumonia (LIP) associated with polyclonal gammopathy and selective depression of cellular immunity. Enhanced humoral immunity is suggested because the patient exhibited increased levels of circulating immunoglobulin (chiefly IgG) and a positive test reaction for rheumatoid factor. When first examined, the patient displayed depressed cellular immunity in that the results of his skin test were negative to dinitrochlorobenzene and phytohemagglutinin (PHA), his peripheral lymphocytes responded suboptimally to PHA, and he had decreased numbers of circulating T cells. When examined 6 yr later, the patient was again hypergammaglobulinemic, but he had regained some of his cellular immune function. Eight years after the patient was initially seen, he showed further improvement in cellular immune function. Analysis of bronchoalveolar lavage cells showed that the patient had a normal proportion of OKT4+ (inducer/helper) cells, but a reduced number of OKT8+ (suppressor/cytotoxic) cells. Thus, his improvement may have been associated with a correction of an imbalance of immunoregulatory T cells. Furthermore, because the disease was active on initial examination but less active after the second evaluation, malfunction of his cellular immune functions may have been involved in the pathogenesis of LIP.

Humans↗

PubMed1996

Pilot study of combined cryosupernatant and protein A immunoadsorption exchange in the treatment of grade 3-4 bone marrow transplant-associated thrombotic microangiopathy.

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) ranges in severity from a self-limiting to a fatal disorder. There is no specific therapy for this condition to date. We have previously described a simple clinical grading system (grade 0-4) for BMT-TM; patients with grade 3-4 BMT-TM do poorly. A previous study in our institution suggested that a combination of exchange with cryosupernatant replacement and protein-A immunoadsorption (PAI) might be of benefit. Therefore we performed a pilot study to evaluate the effectiveness of cryosupernatant alternating with PAI exchange for 2 weeks in a series of 13 patients with grade 3-4 BMT-TM. Twelve of 13 patients had undergone allogeneic-BMT a median of 25 days (range of 5-458 days) prior to the onset of grade 3-4 BMT-TM. The thirteenth patient had undergone autologous peripheral stem cell transplant 11 days prior to grade 4 BMT-TM. Pre-therapy, 10 patients had grade 4 BMT-TM and three had grade 3. Eight (62%) showed a response to treatment. Post-therapy, four responders had grade 3, three had grade 2 and one had grade 0 BMT-TM. The median follow-up of the responders is 90 days (range 21 to 464). Three responders have died at 21, 44, and 226 days following the development of BMT-TM of interstitial pneumonia in one, aspergillus in one, and multiorgan failure syndrome (MOFS) in one. The remaining responders are alive 66-465 days post-TM. All non-responders died of MOFS at 6-31 days post-TM. These results suggest that combined exchange with cryosupernatant alternating with PAI is effective therapy for some patients with moderate to severe BMT-TM and may improve survival.

Adult↗

PubMed1995

Steroid-responsive pulmonary disorders associated with myelodysplastic syndromes with der(1q;7p) chromosomal abnormality.

We report three patients with pulmonary disorders associated with myelodysplastic syndromes (MDS). All three patients had symptoms of pyrexia and respiratory discomfort. One patient had pulmonary eosinophilia with bilateral pleural effusion, one had interstitial pneumonia, and one had bilateral pleural effusion caused by systemic vasculitis. Elevated C-reactive protein (CRP) levels, polyclonal hypergammaglobulinemia, and morphological abnormalities in peripheral blood were observed in all three patients. The bone marrow of these patients revealed trilineage dysplasia and eosinophilia. Cytogenetic analysis showed [46,XY,-7,+der(1q;7p)]. Antibiotic treatment was not effective. However, improvement was dramatic after corticosteroid treatment; CRP levels were reduced and the hypergammaglobulinemia was improved. These cases suggest that MDS with [-7,+der(1q;7p)] may be correlated with bone marrow eosinophilia and that an immunologic abnormality may be involved in the pulmonary disorders.

Adrenal Cortex Hormones↗

PubMed1985

Serum lactate dehydrogenase levels in adults and children with acquired immune deficiency syndrome (AIDS) and AIDS-related complex: possible indicator of B cell lymphoproliferation and disease activity. Effect of intravenous gammaglobulin on enzyme levels.

Twenty-seven of 33 patients with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex (16 adults and 17 children) demonstrated significant elevation of serum lactate dehydrogenase activity, occurring in the isomorphic distribution. Serum lactate dehydrogenase activity was the highest in all nine patients with acute Pneumocystis carinii pneumonitis, in seven of whom extensive interstitial pulmonary infiltrates with lymphocytes and plasma cells were documented. Lactate dehydrogenase activity was also significantly elevated on a long-term basis in all 17 pediatric patients with non-Pneumocystis lymphoid interstitial pneumonitis. Clinical resolution of Pneumocystis carinii pneumonitis was associated with a decline in lactate dehydrogenase activity. Periodic intravenous gammaglobulin was more effective than conventional therapy (trimethoprim/sulfamethoxazole and pentamidine) in achieving clinical and immunologic improvement and reduction of serum lactate dehydrogenase activity in patients with Pneumocystis carinii pneumonitis. Intravenous gammaglobulin was also more effective in patients with AIDS and non-Pneumocystis carinii pneumonitis and lymphoid interstitial pneumonitis. Lactate dehydrogenase activity declined to normal, at least temporarily, in nine of 12 intravenous gammaglobulin-treated patients as compared with only two of 12 untreated patients. Six adult patients with AIDS or AIDS-related complex and no interstitial pneumonitis exhibited normal lactate dehydrogenase levels. These findings suggest that serum lactate dehydrogenase activity in patients with AIDS or AIDS-related complex may be a useful indicator of pulmonary interstitial inflammation. As such, it may be utilized to predict disease course and monitor response to intravenous gammaglobulin treatment.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Bronchointerstitial pneumonia and respiratory distress in young horses: clinical, clinicopathologic, radiographic, and pathological findings in 23 cases (1984-1989).

Twenty-three foals, between 1 and 7 months old, with signs of acute respiratory distress, were examined at the Veterinary Medical Teaching Hospital (VMTH), University of California, Davis, between 1984 and 1989. Characteristic features included sudden onset of severe respiratory distress and tachypnea, cyanosis unresponsive to nasal oxygen, pyrexia, hypoxemia, hypercapneic respiratory acidosis, poor response to treatment, and histopathologic lesions of bronchiolitis and bronchointerstitial pneumonia. Seven of the 23 foals were normal before the onset of respiratory distress, 3 foals were found dead, and 13 foals were being treated for respiratory tract infections at the time of presentation. Laboratory data obtained for 13 horses showed increased plasma fibrinogen concentration (630.7 +/- 193 mg/dL), leukocytosis (18,607 +/- 7,784/microL), and neutrophilia (13,737 +/- 8,211/microL). Thoracic radiographs showed a diffuse increase in interstitial and bronchointerstitial pulmonary opacity and, in 5 foals, an alveolar pulmonary pattern of increased density was also seen. In 3 foals heavy interstitial infiltration proceeded to a coalescing nodular radiographic appearance. Microbiological culture of tracheobronchial aspirates (TBA) from 9 foals yielded bacterial growth, but no one bacterial species was consistently isolated. Microbiological culture of postmortem specimens of the lung from 6 foals yielded growth of bacteria that included Escherichia coli, Enterobacter spp., Proteus mirabilis, Klebsiella pneumoniae, Rhodococcus equi, or beta-hemolytic Streptococcus spp. Tracheobronchial aspirates from 4 foals and lung samples collected from a further 4 foals at necropsy yielded no bacterial growth. Cultures were not taken from two foals premortem or postmortem. Virologic examination of TBA, lung tissue, or pooled organ tissue from 12 foals was negative. Viral culture of TBA from 1 foal showed cytopathic effects and positive immunofluorescence for equine herpes virus type II (EHV-II). In addition to the 3 foals that were found dead, 11 foals died or were euthanatized. Pathologic lesions were limited to the lungs in 50% of the foals; the remainder also had bowel lesions suggestive of hypoxic injury. The predominant histopathologic pulmonary lesions included bronchiolitis, bronchiolar and alveolar epithelial hyperplasia, and necrosis. Many bronchioles were filled with mucoid and fibrinocellular exudate. The peribronchiolar interstitium and adjacent alveolar spaces were also infiltrated with inflammatory cells and contained proteinaceous edema fluid. Type II cell hyperplasia and hyaline membrane formation were observed in the majority of foals and in 2 foals alveolar multinucleate giant cells were also present.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2003

[Current views of tuberculosis inflammation].

The value of histological and histochemical studies in the diagnosis of a phase of tuberculosis progression or healing is shown. Electron microscopic study of tuberculous inflammation in different phases of its evolution evaluated the functional status of cellular elements of the lung and granuloma. The body's antituberculous resistance due to molecular genetic mechanisms is realized through intercellular interactions and macrophageal functions. Immune macrophages are characterized by a higher metabolic activity, they suppress the intracellular multiplication of Mycobacterium tuberculosis (MBT) and are more protected from their toxic action. The pathogenetic mechanisms responsible for caseous pneumonia were studied. Three stages of evolution of the process: Stage 1 is the breakdown of defense and adaptive mechanisms: disorganization of connective tissue and alveolar parenchyma; enhanced permeability of blood and lymphatic microvascular walls with developed interstitial and intraalveolar edema, plasma and fibrin exudation, fibrinoid swelling of collagenous fibers, and their lysis; occurrence of lung parenchymal microinfarcts and infarction-pneumonia; type 2 alveolocytic dysfunction with surfactant destruction; Stage 2 is the breakdown of local immunity; exudative and alterative tuberculous inflammation with involvement of immunocompetent organs; suppressed T-cellular immunity, a shift of a T helper/T suppressor ratio to the latter, lymphopenia; impaired intercellular interactions, cellular apoptosis in blood and inflammation areas, and suppressed granulomatous reaction; inhibited L transformation of Mycobacteria tuberculosis, intensive MBT multiplication in the foci of tuberculous inflammation, particularly those which are resistant to many antibiotic drugs, a larger number of associations of the nonspecific microflora and fungi. Stage 3 is caseous pneumonia and generalization of a tuberculous process: a predominance of an alterative reaction of inflammation; the presence of allergic and caseous and necrotic vasculitis, bronchiolitis, and endo-panbronchitis; depressed granulomatous reaction; the development of acute alterative sequestrating pneumoniogenic caverns. Histological, histochemical, and electron microscopic studies of tuberculous inflammation may specify the mechanisms of the pathogenesis of tuberculosis and may serve as the basis for early diagnosis of the disease and for timely correction of performed treatment in order to enhance its efficiency.

Giant Cells↗

PubMed1976

Cardiac pathologic findings in patients treated with bone marrow transplantation.

Cardiac pathologic findings were analyzed in 22 necropsy cases from a series of 29 patients with leukemia, aplastic anemia, or metastatic cancer who had been treated with ablative therapy followed by bone marrow transplantation. Some cardiac alterations were similar to those that occur in patients with hematologic and neoplastic diseases not treated with bone marrow transplantation, and consisted of cardiomegaly, cardiac atrophy, hemorrhage, foci of necrosis due to shock associated with sepsis or hepatic failure, myocardial abscesses secondary to systemic candidiasis or staphylococcal infection, fibrinous pericarditis, and hemosiderosis. Other cardiac alterations were more specifically related to factors associated with transplantation procedure. Six patients exhibited a distinctive interstitial reactive change characterized by the presence of (1) moderate to large numbers of Anitschkow cells, occurring alone or in small cellular aggregates and histiocytes, histiocytic cells with nuclei of the Anitschkow type, lymphoid cells, and plasma cells, and (2) nuclei of the Anitschkow type in cardiac vascular and endocardial smooth muscle, endothelial and Schwann cells, and occasional cardiac muscle cells. This alteration may have been induced by abnormal immune mechanisms, as suggested by the observation that five of the six patients with interstitial change had clinical evidence of graft-versus-host disease. Two patients developed fatal congestive cardiac failure in the early post-transplant period and exhibited myocardial damage with histologic and post-transplant period features indicative of severe acute injury. Findings in these two patients consisted of necrotic muscle cells, which exhibited multiple contraction bands, diastase-resistant PAS staining, and intracellular fibrin deposits; microthrombi, which were composed of fibrin and occasionally of fibrin and platelets; and extravasated erythrocytes and fibrin strands in the interstitium. One of the two patients also exhibited unusual nuclear alterations, which were characterized by replacement of normal chromatin by palely stained fibrous and filamentous material. Clinicopathologic analysis strongly suggested that the fatal cardiotoxicity in both patients resulted primarily from effects of high doses of cyclophosphamide, which were administered as part of a four drug regimen that provided tumor ablation and immunosuppression for bone marrow transplantation. Our findings emphasize the need for less toxic antineoplastic and immunosuppressive therapy for use in bone marrow transplantation procedures.

Abscess↗

PubMed1993

Early events in immune evasion by the lentivirus maedi-visna occurring within infected lymphoid tissue.

Infections caused by lentiviruses, including human immunodeficiency virus, are characterized by slowly progressive disease in the presence of a virus-specific immune response. The earliest events in the virus-host interaction are likely to be important in determining disease establishment and progression, and the kinetics of these early events following lentiviral infection are described here. Lymphatic cannulation in the sheep has been used to monitor both the virus and the immune response in efferent lymph after infection of the node with maedi-visna virus (MVV). Viral replication and dissemination could be detected and consisted of a wave of MVV-infected cells leaving the node around 9 to 18 days postinfection. No cell-free virus was recovered despite the fact that soluble MVV p25 was detected in lymph plasma. The maximum frequency of MVV-infected cells was only 11 in 10(6) but over the first 20 days of infection amounted to greater than 10(4) virus-infected cells leaving the node. There was a profound increase in the output of activated lymphoblast from the lymph nodes of infected sheep, characterized by an increased percentage of CD8+ lymphoblasts. All of the CD8+ lymphoblasts at the peak of the response expressed both major histocompatibility complex class II DR and DQ molecules but not interleukin-2 receptor (CD25). The in vitro proliferative response of efferent lymph cells existing the node after challenge with MVV to both recombinant human interleukin-2 and the mitogen concanavalin A was decreased between days 8 and 16 postinfection, and a specific proliferative response to MVV was not detected until after day 15. Despite the high level of CD8+ lymphoblasts in efferent lymph, direct MVV-specific cytotoxic activity was demonstrated in only one of the five MVV-challenged sheep. MVV-specific antibody responses, including neutralization and MVV p25 immune complexes in efferent lymph, were detectable during the major period of virus dissemination. The relationship of these findings to the evasion of the host's acute immune response by MVV is discussed.

Animals↗

PubMed1993

Immunofluorescent analysis of plasma fibronectin incorporation into the lung during acute inflammatory vascular injury.

Incorporation of plasma fibronectin into tissues is believed to influence endothelial cell-cell interaction, as well as endothelial cell adhesion to matrix. We used immunofluorescent microscopy coupled with tissue extraction of noncovalently incorporated fibronectin to delineate the time course for matrix incorporation of soluble plasma-derived fibronectin into the lung of sheep during postoperative bacteremia. Adult sheep were surgically prepared with both lung and peripheral lymph fistulas. Sheep were anesthetized 2 days following surgery and injected intravenously with a sublethal dose of live Pseudomonas aeruginosa, which consisted of 5 x 10(8) live organisms suspended in 0.9% saline. Bacterial infusion elicited a 300% increase in lung transvascular protein clearance but no increase in peripheral transvascular protein clearance. Purified dimeric human plasma fibronectin (hFn), used as an "immunologic marker," was then infused intravenously (100 mg/sheep) into two additional groups of sheep (nonbacteremic control group and bacteremic experimental group) and allowed to mix with the plasma pool of endogenous soluble sheep fibronectin (sFn). Incorporation of the plasma-derived hFn into the lung matrix and its distribution in relation to endogenous sheep fibronectin in the matrix was assessed by dual-label immunofluorescence using antibodies specific to either sFn or hFn. Human fibronectin from the vascular compartment codistributed with endogenous sheep fibronectin in the lung matrix. Moreover, its deposition into the lung was markedly increased in postoperative bacteremic sheep compared with nonbacteremic control sheep. Increased hFn deposition in the lung with bacteremia was clearly apparent within 2 h. The hFn deposited in the lung was nonextractable using a heparin-urea tissue extraction buffer, suggesting its rapid covalent cross-linking and incorporation into the lung matrix. Microscopic analysis of serial lung biopsies revealed focal areas of inflammation with an intense mononuclear infiltrate into the lungs by 2 h in the bacteremic sheep. Interstitial edema and vascular endothelial injury were observed by 4 h, with alveolar edema apparent over 6 to 8 h. Thus, postoperative bacteremia results in a rapid incorporation of plasma fibronectin into the lung matrix. This may be a physiologic mechanisms to stabilize the integrity of the lung vascular barrier.

Animals↗