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Biomedical subjects

L Irving

Publications and source records attributed to L Irving.

At least 19 recordsLinked to original sources

Differential protease, innate immunity, and NF-kappaB induction profiles during lung inflammation induced by subchronic cigarette smoke exposure in mice.

Cigarette smoke exposure is a major determinant of adverse lung health, but the molecular processes underlying its effects on inflammation and immunity remain poorly understood. Therefore, we sought to understand whether inflammatory and host defense determinants are affected during subchronic cigarette smoke exposure. Dose-response and time course studies of lungs from Balb/c mice exposed to smoke generated from 3, 6, and 9 cigarettes/day for 4 days showed macrophage- and S100A8-positive neutrophil-rich inflammation in lung tissue and bronchoalveolar lavage (BAL) fluid, matrix metalloproteinase (MMP) and serine protease induction, sustained NF-kappaB translocation and binding, and mucus cell induction but very small numbers of CD3+CD4+ and CD3+CD8+ lymphocytes. Cigarette smoke had no effect on phospho-Akt but caused a small upregulation of phospho-Erk1/2. Activator protein-1 and phospho-p38 MAPK could not be detected. Quantitative real-time PCR showed upregulation of chemokines (macrophage inflammatory protein-2, monocyte chemoattractant protein-1), inflammatory mediators (TNF-alpha, IL-1beta), leukocyte growth and survival factors [granulocyte-macrophage colony-stimulating factor, colony-stimulating factor (CSF)-1, CSF-1 receptor], transforming growth factor-beta, matrix-degrading MMP-9 and MMP-12, and Toll-like receptor (TLR)2, broadly mirroring NF-kappaB activation. No upregulation was observed for MMP-2, urokinase-type plasminogen activator, tissue-type plasminogen activator, and TLRs 3, 4, and 9. In mouse strain comparisons the rank order of susceptibility was Balb/c > C3H/HeJ > 129SvJ > C57BL6. Partition of responses into BAL macrophages vs. lavaged lung strongly implicated macrophages in the inflammatory responses. Strikingly, except for IL-10 and MMP-12, macrophage and lung gene profiles in Balb/c and C57BL/6 mice were very similar. The response pattern we observed suggests that subchronic cigarette smoke exposure may be useful to understand pathogenic mechanisms triggered by cigarette smoke in the lungs including inflammation and alteration of host defense.

Animals↗

Identification of Mycobacterium shimoidei by molecular techniques: case report and summary of the literature.

A 53-year-old woman from Melbourne, Australia, with squamous cell carcinoma of the oesophagus was shown by computed tomography (CT) scan to have a left apical cavity and inflammatory changes in the right lung consistent with aspiration. Acid-fast bacilli isolated from bronchial washings were identified biochemically first as Mycobacterium terrae, but later as M. shimoidei on the basis of 1) restriction fragment analysis and 2) sequencing of polymerase chain reaction (PCR) amplified 16S rDNA. Nine other descriptions of patients with M. shimoidei isolates were collated. The salient feature of isolates considered to be pathogenic was pulmonary cavitation. Most patients had underlying lung disease, including past tuberculosis or malignancy. Six of eight patients died of progressive respiratory illness, although the contribution of M. shimoidei was not always clear, and two patients improved. One patient with the acquired immune-deficiency syndrome (AIDS) died with Salmonella enteritidis and M. shimoidei isolated from blood cultures. One isolate was regarded as a coloniser. There are insufficient clinical or sensitivity data on which to base recommendations for therapy, but a combination of ethambutol, rifabutin and pyrazinamide could be considered.

AIDS-Related Opportunistic Infections↗

HIV-1 DNA and mRNA concentrations are similar in peripheral blood monocytes and alveolar macrophages in HIV-1-infected individuals.

OBJECTIVE: To determine the relative contribution of alveolar macrophages, peripheral blood monocytes (PBM) and peripheral blood lymphocytes (PBL) from HIV-infected individuals to HIV-1 viral load. METHODS: Alveolar macrophages were obtained by flexible bronchoscopy, and PBM and PBL by venipuncture from HIV-1-infected individuals. Alveolar macrophages and PBM were purified using immunomagnetic bead selection to deplete CD3+ and CD19+ cells from bronchoalveolar lavage and peripheral blood mononuclear cells, respectively. DNA and mRNA were extracted and gag copy number quantified using polymerase chain reaction (PCR) and reverse transcriptase PCR. The titres of infectious cell-associated HIV-1 in cells were determined by the endpoint dilution coculture technique for alveolar macrophages and PBM. RESULTS: Alveolar macrophages and PBM from HIV-1-infected subjects (n=11) contained equivalent concentrations of HIV-1 DNA and HIV-1 mRNA as determined by PCR and reverse transcriptase PCR, respectively. Antiretroviral therapy was associated with reduced viral DNA concentrations in alveolar macrophages but not in PBM. PBL had a significantly higher level of proviral DNA and mRNA than alveolar macrophages or PBM. CONCLUSIONS: Although alveolar macrophages infected in vitro are more permissive for HIV-1 replication than PBM, this difference could not be demonstrated in vivo.

Cells, Cultured↗

Blanket use of intranasal mupirocin for outbreak control and long-term prophylaxis of endemic methicillin-resistant Staphylococcus aureus in an open ward.

In December 1992, a thoracic ward in a Melbourne teaching hospital experienced an increase in patients infected with methicillin-resistant Staphylococcus aureus (MRSA). It was decided to attempt to control the outbreak by cohorting positive patients (infected and colonized), as well as nurse cohorting, emphasis on handwashing, and use of intranasal mupirocin initially three times a day for three days, then thrice weekly, for all patients in the ward (with or without MRSA). The campaign comprised for phases of 53, 45, 92 and 365 days, respectively. Patient and nurse cohorting stopped at the end of phase I. In phases I and II, surveillance nose swabs were taken on admission, then twice weekly; in phase III, on admission and weekly and in phase IV, on admission until the end of 1993. In phases I and II (98 days), only one patient acquired MRSA. When the frequency of mupirocin prophylaxis was decreased to once weekly (phase III), two patients acquired MRSA in 92 days (no significant difference): thrice weekly administration resumed (phase IV), during which there were three acquisitions in 365 days. The rates of nose colonization of admissions were 6.4%, 6.3%, 9.7% and 3.1% in phase I-IV, respectively. Only three patients were treated with vancomycin between July 1993 and June 1994 (significantly lower than historical rates, P = 0.0086). No mupirocin resistance was seen in MRSA isolates from this ward during phases I, II and III. In areas of low-level endemic MRSA, the blanket use of thrice-weekly intranasal mupirocin may be effective in decreasing serious infections with MRSA, and does not necessarily elicit mupirocin resistance.

Administration, Intranasal↗

Update on lung cancer.

Lung cancer is common, largely smoking related and thus preventable. Focal non small cell disease is surgically resectable but presentation with mediastinal and metastatic disease is common and has a poor prognosis. Small cell lung cancer is chemosensitive but has a very poor prognosis. Widespread screening programs are not currently considered cost-effective. New preventive and therapeutic approaches are the way forward and a multidisciplinary approach is clearly needed.

Humans↗

The kinetics of surface expression of CD11/CD18 integrins and CD54 on monocytes and macrophages.

Cells of the macrophage lineage mediate extremely important normal functions of the immune system. Such functions are in part related to interactions between cell-bound LeuCAMs and their ligands. MoAb staining and flow cytometric analysis were used to follow changes in surface expression of LeuCAMs and the LFA-1 ligand CD54 during maturation of peripheral blood monocytes (BM) in vitro. Surface expression of these molecules increased on BM following isolation, the greatest increase being in CD54 and CD11c. Following an initial increase, there was a reduction in CD11a expression after 2 weeks in culture, this being greater on adherent compared with suspension-maintained cells. Expression of CD11b remained high throughout the culture period. LeuCAM and CD54 expression was further compared on freshly isolated alveolar macrophages (AM) and BM paired donors. A reciprocal relationship was observed between CD11c and CD11b on AM and BM, in that BM expressed higher levels of CD11b than CD11c, whilst the converse was true for AM. CD54 expression was also higher on AM than on BM, whilst there was no significant difference in expression of CD11a on these cells. These data suggest that consistent changes occur in the surface expression of the LeuCAMs and CD54 as monocytes mature into macrophages, which may reflect the specific functions of these cells.

CD11 Antigens↗

Chromosome abnormalities in non-small cell lung cancer pleural effusions: cytogenetic indicators of disease subgroups.

A cytogenetic study of pleural effusions (PE) containing metastatic or invasive tumor cells from 11 patients with non-small cell lung cancer (NSCLC) (3 squamous cell carcinomas [SQC] and 8 adenocarcinomas [ADC] including 1 giant cell variant) was performed to identify non-random chromosome abnormalities. Numerical abnormalities seen in > or = 30% of cases included gain of chromosomes 7 and 20, and loss of chromosomes 4, 9, 10, 13, 15, 16, 18, 19, 21, and 22. The most frequent structural abnormality involved rearrangement in 1p with breakpoints clustering at 1p10-p13. Other recurrent breakpoint regions, seen in > or = 30% of cases, occurred in chromosome region 3p10-p21, 3q11-q25, 6p11-p25, 6q13-q23, 7q11-q36, 9q32-q34, 11p11-p13, 11q13-q24, 13p/14p and/or 15p, 17p and 19p, with, in particular, apparent loss of 6q21-q27, 3p21-p26, 7q21-q22, 9p22-p24 (shortest regions of common overlap) and 17p. There was also recurrent gain of 1q23-q44, 8q13-q24, and 11q13-q23. These abnormalities were not restricted to a particular histological subtype, with the exception of +8 and a breakpoint in 9q32-q34, which were seen only in ADC. The 9q32-q34 breakpoint observed in 4 ADC PE (including 1 giant cell variant) represents a new observation in NSCLC. These findings, when compared to those reported for primary NSCLC indicate cytogenetic differences between the two which may be associated with pleural invasion of NSCLC.

Adenocarcinoma↗

Pneumomediastinum after a transbronchial biopsy.

A pneumomediastinum occurred after a transbronchial biopsy in a woman with pulmonary fibrosis and was confirmed by computed tomography. Although pneumomediastinum has a pathogenesis similar to that of pneumothorax it has not been reported after transbronchial biopsy.

Biopsy↗

Cytogenetics of non-small cell lung cancer: analysis of consistent non-random abnormalities.

Cytogenetic analysis of ten primary non-small cell lung carcinomas (NSCLC), including five adenocarcinomas (ADC), three squamous cell (SQC), and two large cell (LCC) carcinomas has been carried out in an attempt to determine karyotype changes involved in the early stage of disease. The tumors were all aneuploid and exhibited complex karyotypes with multiple structural and numerical abnormalities. Clonal structural rearrangements were identified and in particular loss of material from the short arm of chromosome 9 had a 90% incidence. This loss was due to non-reciprocal translocation, deletion, or chromosome loss. Breakpoints were in the region 9q13 to p22. Other chromosome regions that were non-randomly involved are as follows: I cen to p13, 3p, 5q11 to q13, 6p, 6q15 to q27, 7p, 8p, 11q12 to q23, 13p, 14p, 15p, 17p, and 19p. While a primary cytogenetic change in NSCLC has not been identified conclusively, our findings implicate loss of material from 9p as a potentially important event.

Aneuploidy↗

Serum levels of beta-carotene, vitamin A, and zinc in male lung cancer cases and controls.

The mean serum levels of beta-carotene and vitamin A in a multivariate analysis of data from 64 histologically confirmed male lung cancer cases were statistically significantly lower than those from 63 randomly selected male hospital controls, who were admitted for small surgical operations (p values for both beta-carotene and vitamin A less than 0.001). The mean serum levels of zinc were not statistically significantly different between cases and controls (p = 0.10). The levels of beta-carotene, vitamin A, or zinc were not statistically significantly influenced by either the extent of the cancer (p = 0.45) or the cancer cell type (p = 0.06). The possible biological significance of these findings is discussed briefly.

Adenocarcinoma↗

Adenovirus eye infections in an Australian city, 1972-9.

A number of adenovirus serotypes have been associated with both sporadic cases and outbreaks of conjunctivitis and pharyngoconjunctival fever but only adenovirus type 8 and adenovirus type 19 have been responsible for wide-spread epidemic kerato-conjunctivitis. In Melbourne, Australia, in the past eight years these two serotypes have been prevalent, resulting in an outbreak of adenovirus type 8 kerato-conjunctivitis in 1976-7 followed by adenovirus type 19 kerato-conjunctivitis in 1978-9. During these two periods of peak incidence, 53 cases of adenovirus type 8 and 43 cases of adenovirus type 19 kerato-conjunctivitis were confirmed by isolation.

Adenoviridae Infections↗

Metabolism and temperature regulation in young harbor seals Phoca vitulina richardi.

Metabolism and the ability to regulate core and peripheral temperatures under a variety of ambient conditions were studied in five unrestrained pups (less than 5 wk old) and four 3- to 5-mo-old harbor seals. Pups born with nonlanugo (adultlike) hair and little fat were able to swim in 5 degrees C water for several hours without becoming hypothermic. They were also found to tolerate 5 degrees C air temperature with the fur wet and exposed to a 35-knot wind. Basal metabolism in pups averaged 0.8 ml O2 g-1 h-1, which is 2.6 times the predicted value for an adult mammal of the same weight. Lower critical temperature in air was about 3 degrees C. Oxygen uptake in 3- to 5-mo-old seals under basal conditions was 0.5 ml g-1 h-1. Minimal thermal conductance values were .02 and .015 ml O2 g-1 h-1 degrees C-1 in pumps and 3- to 5-month-old seals, respectively. Appendages, and to a lesser extent the skin on the torso, cooled appreciably at lower air temperatures, and the flippers were kept just above freezing in subzero air. Tissue insulation provided by low peripheral temperatures and a high resting metabolic rate enable newborn and developing harbor seals to tolerate the low temperatures encountered in their natural environment.

Animals↗

Motion of both mitral valve leaflets: a cineroentgenographic study in intact dogs.

Motion and position of both mitral leaflets were studied in five normal dogs 1-11 wk after radiopaque markers were sutured on the valve cusps and on the mitral annulus. Cinefluorograms and cineangiograms (100-120 frames/s) of left atrium and left ventricle were used to study cusp motion and intraventricular flow patterns, and to detect mitral regurgitation during sinus rhythm (42-184 beats/min) and during isolated atrial or ventricular contractions. Time-motion of both leaflets was similar throughout diastole with the exception of delayed posterior cusp opening. Peak opening and closing speeds, opening and closing times, and time of complete closure, measured from the Q wave of the ECG, were not significantly affected by the variations in heart rate. Diastolic leaflet closure began immediately after opening, while the ventricular cavity was small, and was caused by flow eddies behind the cusps. Isolated ventricular contractions closed the valve leaflets completely and symmetric valve closure was ensured by the different rates of leaflet edge approximation. In contrast, atrial closure was slow, partial, and of very short duration.

Animals↗