Biomedical subjects
Publications and source records attributed to R M Rose.
This article describes the epidemiology, transmission, and pathophysiology of viral infection of the lower respiratory tract. Current approaches to diagnosis, treatment, and prevention also are discussed.
From a prospective study of health changes in air traffic controllers, it was determined that high scores on self-report measures of work-related life change distress, other life changes outside the work setting, the type A behavior pattern, and dissatisfaction with management were positively related to future rates of injuries and physician-diagnosed acute illness episodes. Depending on the risk factor involved, high scorers on these psychosocial risk predictors incurred from 80% to 252% more future accidental injuries and from 38% to 69% more future total morbidity over a 27-month follow-up period than the men in the low scoring groups. Moreover, coworker-rated amicability, probably an indication of the amount of social support available to an individual, was significantly protective against these outcome variables, with the rarely or never chosen group experiencing 60% more total morbidity and 174% more injuries than the often chosen group. A multiple-regression equation revealed that stress, amicability, type A, and satisfaction with management had an additive effect on the outcome variables. Work- and non-work-related life change distress subscales were similar in their ability to predict later morbidity. Prediction was stronger for 27-month follow-up than for only the first 9-month period. The findings, if replicated, raise the possibility of screening programs to identify employees at high risk of future illness and injury.
A majority of pediatric patients and rare adult patients with the acquired immunodeficiency syndrome (AIDS) develop a chronic respiratory disorder referred to as "lymphocytic interstitial pneumonitis" (LIP). Efforts to identify an infectious agent responsible for this process so far have failed. In this study, frozen sections of lungs from patients with AIDS and pulmonary disease were tested by in situ molecular hybridization for the presence of cells infected with human T-cell lymphotropic virus type III (HTLV-III) and expressing viral RNA. In the case of an infant with LIP, a relatively high frequency (0.1%) of cells in the lung were found to be positive for HTLV-III RNA. This number is the lower limit of total cells infected since the in situ hybridization technique as applied in this study depends on expression of HTLV-III genes, and previous evidence indicates that a proportion of cells infected with HTLV-III may not express viral RNA. Moreover, this degree of infection of the lung is likely limited to LIP, since in ten patients with AIDS and pulmonary diseases other than LIP, only 0% to 0.002% of cells in lung were positive for viral RNA expression. Thus, HTLV-III may play a direct causal role in the development of LIP in infected patients, implicating its involvement in yet another of the diverse clinical diseases associated with this virus.
Based on experience with three cases of endobronchial non-Hodgkin's lymphoma and a review of cases previously reported, two patterns of lymphomatous involvement of airways are described. The Type 1 pattern is characterized by diffuse submucosal infiltrates occurring in the presence of intra- and extrathoracic lymphoma. In Type 2 cases, central airways are involved by a solitary mass in the absence of clinically apparent systemic lymphoma. The clinical-radiologic picture is characterized by signs of pneumonitis in Type 1 cases, while in Type 2 cases, signs of airway obstruction uniformly occur.
Guinea pigs were inoculated by the respiratory route with wild-type (Cyr) or vaccine (Oka) strain varicella zoster virus (VZV). Wild-type cell-free virus obtained by sonication produced neutralizing antibody responses in steroid-treated animals when given via the intratracheal route, and induced neutralizing antibody as well as a pneumonitis in normal animals when given via the intrabronchial (i.b.) route. A humoral response also followed i.b. instillation of cell-associated wild-type or vaccine strain VZV. Prior i.b. administration of thioglycollate or exposure to hyperoxia altered the number and function of pulmonary macrophages, respectively, but viral susceptibility of the guinea pigs was not enhanced. Both strains of VZV could be isolated from bronchial washings up to 48 hours after i.b. instillation of cell-associated virus, but neither strain was isolated thereafter from cultures of bronchial washings or explanted lung tissues.
Supernatants from concanavalin A-stimulated human peripheral blood mononuclear cells were fractionated by gel filtration and isoelectric focusing. A fraction with an isoelectric point of 2.2-3.3 containing macrophage migration inhibition factor activity inhibited the replication of herpes simplex virus type 1 in human pulmonary macrophages and U937 cells. This fraction did not inhibit the replication of herpes simplex virus in human fibroblasts. Moreover, the ability of this lymphokine fraction to inhibit viral growth in macrophages was not neutralized by antibody against interferon-gamma. These findings identify a macrophage specific antiviral lymphokine which is distinct biochemically and immunologically from interferon-gamma.
New methods for determination of specific concentration and molecular activity of monoamine oxidase (MAO) in platelets are described and evaluated in parallel with specific activity measures, performed in whole platelets and platelet extracts. Platelet MAO specific concentration is determined in platelet extracts by a radioimmunoassay, using a monoclonal antibody that recognizes human MAO B, the form that occurs in platelets, but not MAO A. All four platelet MAO measures are found to be reliable and stable, and thus are suitable for long-term comparisons of normal and clinical populations, such as those reported in Part II of this report. The new measures of enzyme concentration and molecular activity make available important information about the state of MAO B molecules in a given individual that reflects the genetic expression and control of the enzyme.
Platelet monoamine oxidase (MAO B) in 59 normal and 57 RDC-diagnosed medicated and unmedicated schizophrenic subjects was analyzed for whole platelet and extracted activities, specific concentration, and molecular activity. A novel radioimmunoassay using a monoclonal antibody elicited to human platelet MAO was used. Female schizophrenics showed no differences from female normals in MAO measures; however, these data could not be clearly evaluated because of confounding effects of age and drugs. Male schizophrenics treated with neuroleptics expressed significantly reduced whole platelet MAO activity, compared to untreated male patients. Compared with normal males, male schizophrenics showed significantly lowered molecular activities, along with elevated specific concentrations, which did not appear to be explained solely by drug usage. Additional mechanisms explaining the diminished molecular activity in male schizophrenics may be the presence of an endogenous irreversible inhibitor or a genetically determined, possibly structural, variant of MAO B.
The ability of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and gamma interferon (IFN-gamma) to modify human immunodeficiency virus (HIV; also called HTLV-III/LAV) infection in the monocytic cell line U-937 was examined. When added to persistently infected cell cultures, GM-CSF at 30-300 units per ml produced maximal reductions in reverse transcriptase activity of 37-55% 10-14 days after its addition, whereas IFN-gamma produced reductions of 64-68% 10-17 days after addition. When used prior to acute HIV infection and maintained in the cell culture system, these cytokines reduced reverse transcriptase activity 90-100% and nearly eliminated viral antigen expression but did not prevent return of productive infection after their removal. These results indicate that, in a monocyte model of HIV infection, GM-CSF and IFN-gamma substantially restrict HIV expression and that these cytokines deserve further evaluation as therapeutic alternatives in HIV-related disorders.
The antiviral function of pulmonary macrophages obtained by broncholavage of healthy smokers and nonsmokers was studied. Compared with nonsmokers' cells, smokers' macrophages produced significantly more virus during in vitro infection with herpes simplex virus type 1 (HSV-1). Exposure of macrophages to either antiviral macrophage-activating factor or interferon-gamma for 20 hr before infection resulted in diminished production of HSV-1 by both types of macrophages. However, in contrast to smokers' cells, exposure of nonsmokers' macrophages to these antiviral lymphokines totally prevented viral replication. This difference could not be attributed to diminished adsorption of virus to smokers' macrophages or to an increased proportion of extracellular to intracellular virus in smokers' cell cultures. The effect of smoking on viral infectivity did not appear to be mediated by secretion of a soluble factor by the macrophage because incubation of nonsmokers' cells with supernatant from smokers' cell cultures did not affect the growth of HSV-1.
Pulmonary complications following orthotopic liver transplantation (OLT) were prospectively evaluated in 18 individuals transplanted at the New England Deaconess Hospital. Of sixteen patients who survived the immediate postoperative period, 12 (75%) sustained a pulmonary complication. Of these complications, 64% were noninfectious--whereas 22% were infectious, and 14% probably infectious. Six of eight documented infections were caused by viruses of the herpes group. In four cases of viral pneumonitis other pulmonary pathogens were isolated (fungi-3, protozoan-1, bacteria-1). Unlike noninfectious complications, pulmonary infections were associated with a fatal outcome in five of six patients who died after OLT. Pulmonary complications are frequent and serious occurrences after OLT, and contribute to both the morbidity and mortality of this procedure. Compared with pulmonary complications seen after transplantation of other organs, OLT was associated with a higher proportion of noninfectious complications but a similar spectrum of pulmonary infections.
In a group of 61 patients admitted to New England Deaconess Hospital, Boston, with a diagnosis of acquired immune deficiency syndrome (AIDS), 25 were found to have Kaposi's sarcoma involving the skin and mucous membranes. Of these 25 patients, eight had lesions involving the respiratory system. Radiographically, patients with Kaposi's sarcoma had hilar and mediastinal adenopathy with perihilar parenchymal infiltration which progressed to diffuse bilateral infiltrates over a period of months. This pattern and the tempo of its evolution were distinctly different from the diffuse infiltrates seen in patients with Pneumocystis carinii pneumonia. Bronchoscopy was performed in seven of the eight patients, revealing characteristic lesions of Kaposi's sarcoma in the airways. We propose that parenchymal pulmonary Kaposi's sarcoma can be strongly suspected in a patient with AIDS who has the following features: a characteristic radiologic pattern; endobronchial Kaposi's sarcoma at bronchoscopy; and no evidence of opportunistic infection. In this subset of patients, further diagnostic intervention such as open lung biopsy, a procedure with potential morbidity in these ill individuals, may be unnecessary.
The human T-cell lymphotropic virus type III (HTLV-III) is the etiologic agent of the acquired immunodeficiency syndrome (AIDS) and preferentially infects T4 lymphocytes. Other cell types, notably B lymphocytes and other nonlymphoid cells, also have been reported to be infected in vitro by HTLV-III. We now report on the susceptibility of human pulmonary macrophages to infection with HTLV-III in vitro. Alveolar macrophages infected with HTLV-III produced low levels of virus that could be transferred to allogeneic human peripheral blood mononuclear leukocytes as long as 2 weeks after initiation of infection. Unlike HTLV-III infection of T lymphocytes, macrophages appeared more resistant to viral-mediated cytopathic effects. Primary cultures of pulmonary macrophages from two of four patients with AIDS spontaneously produced low levels of virus detected as precipitable reverse transcriptase activity, suggesting that these cells were infected in vivo. Because tissue macrophages are long-lived cells, they may act as a reservoir of HTLV-III, capable of transmitting the virus to other susceptible cells such as T lymphocytes, causing periodic low-level viremia. Macrophage infection with HTLV-III may be one mechanism for the establishment of viral persistence in infected hosts.
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Osteoarthrosis is a physiologic imbalance, a "joint failure" similar to "heart failure," in which mechanical factors play a role. The initiation and progression of cartilage damage are distinct phenomena. One of the mechanisms of initiation may be a steep stiffness gradient in the underlying subchondral bone. Progression of cartilage lesions probably requires stiffened subchondral bone. In such situations, transverse stresses at the base of the articular cartilage could cause deep horizontal splits in that tissue. The most likely cause of subchondral stiffening in an otherwise congruent joint is repeated failure of the musculoskeletal peak dynamic force attenuation mechanisms. The health and integrity of the overlying articular cartilage depends on the mechanical properties of its bony bed. In certain models of osteoarthrosis, alterations of the bony bed occur before the cartilage changes and suggest that this can occur in clinical conditions. Stiffening of the subchondral bone also can effect joint conformation, which involves deformation of articular cartilage and bone to create maximum contact areas under load.
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Monoclonal antibodies specific for monoamine oxidase (MAO) A and MAO B, respectively, were used to localize these enzymes in primate brain. The reagents recognized different populations of neurons: those that recognized MAO A were located in cell groups containing catecholamines, including the substantia nigra, nucleus locus coeruleus, nucleus subcoeruleus, and the periventricular region of the hypothalamus, whereas those that recognized MAO B were observed in serotonin regions, including the nucleus raphe dorsalis and nucleus centralis superior. These data illustrate the physiological independence of MAO A and B and show that neurons may be specialized for their degradative as well as their synthetic functions.