Biomedical subjects

G Gudmundsson

Publications and source records attributed to G Gudmundsson.

At least 19 recordsLinked to original sources

PubMed2006

20 years follow-up after the first microsurgical lumbar discectomies in Iceland.

BACKGROUND: Microsurgical discectomies are an established procedure in spinal surgery. This operating technique was first used in the Department of Neurosurgery in Iceland in 1981 and has become standard operative treatment for herniated lumbar discs. There is a great variability in outcome reports regarding recurrence rate and re-operation rate. Few articles are based on follow-up of more than 10 years. This article presents the results of a 20 years follow-up study. METHODS: A retrospective study of all patients undergoing microsurgical discectomy for herniated lumbar disc, from June 1, 1981 to December 31, 1984. Outcome, based on recurrence rate, return to work and patient satisfaction was determined by a self-evaluation questionnaire, phone interviews and patient medical records. FINDINGS: Of the 170 patients, 134 (78.8%) were included in the study (M:F, 58:42%). Preoperative symptoms: back pain with sciatica 108 (80.6%), sciatica 20 (14.9%), back pain 2 (1.5%). Mean follow-up time was 20.7 years (19.5-22.8). Recurrence rate was 12.7%. 19 patients (14.2%) underwent a subsequent lumbar operation at a different level or side. A majority of patients 108 (80.6%) returned to previous level of work, 26 (19.4%) lost some or all working capabilities. Patient satisfaction was high, 91.1% reporting excellent (68.7%) or good (22.4%) results. 5.2% of patients rated the outcome fair and 3.7% poor. Women reported worse outcome than men, excellent M:F 74.7:60.7%, and poor 7.1:1.3%. There was no significant difference in patient satisfaction in patients undergoing additional operations or those with recurrence of the herniated disc. CONCLUSIONS: Outcome was very good with 92.0% return to work and 91.1% patient satisfaction. The recurrence rate was 12.7% with a substantial number of cases occurring 10-20 years after operation. To conclude, microsurgical discectomies maintain a high success rate in the long-term.

Adolescent↗

PubMed2006

Epidemiology of organising pneumonia in Iceland.

BACKGROUND: Cryptogenic organising pneumonia (COP) has also been called idiopathic bronchiolitis obliterans organising pneumonia. In secondary organising pneumonia (SOP) the causes can be identified or it occurs in a characteristic clinical context. The aim of this study was to determine the incidence and epidemiological features of COP and SOP nationwide in Iceland over an extended period. METHODS: A retrospective study of organising pneumonia (OP) in Iceland over 20 years was conducted and the epidemiology and survival were studied. All pathological reports of patients diagnosed with or suspected of having COP or SOP in the period 1984-2003 were identified and the pathology samples were re-evaluated using strict diagnostic criteria. RESULTS: After re-evaluation, 104 patients fulfilled the diagnostic criteria for OP (58 COP and 46 SOP). The mean annual incidence of OP was 1.97/100 000 population (1.10/100 000 for COP and 0.87/100 000 for SOP). The mean age at diagnosis was 67 years with a wide age range. The most common causes of death were lung diseases other than OP, and only one patient died from OP. Patients with OP had a lower rate of survival than the general population, but there was no statistical difference between COP and SOP. CONCLUSIONS: The incidence of OP is higher than previously reported, suggesting that OP needs to be considered as a diagnosis more often than has been done in the past.

Adolescent↗

PubMed2005

Risk factors for rehospitalisation in COPD: role of health status, anxiety and depression.

The aim of the present study was to analyse the risk of rehospitalisation in patients with chronic obstructive pulmonary disease and associated risk factors. This prospective study included 416 patients from a university hospital in each of the five Nordic countries. Data included demographic information, spirometry, comorbidity and 12 month follow-up for 406 patients. The hospital anxiety and depression scale and St. George's Respiratory Questionnaire (SGRQ) were applied to all patients. The number of patients that had a re-admission within 12 months was 246 (60.6%). Patients that had a re-admission had lower lung function and health status. A low forced expiratory volume in one second (FEV1) and health status were independent predictors for re-admission. Hazard ratio (HR; 95% CI) was 0.82 (0.74-0.90) per 10% increase of the predicted FEV1 and 1.06 (1.02-1.10) per 4 units increase in total SGRQ score. The risk of rehospitalisation was also increased in subjects with anxiety (HR 1.76 (1.16-2.68)) and in subjects with low health status (total SGRQ score >60 units). When comparing the different subscales in the SGRQ, the closest relation between the risk of rehospitalisation was seen with the activity scale (HR 1.07 (1.03-1.11) per 4 unit increase). In patients with low health status, anxiety is an important risk factor for rehospitalisation. This may be important for patient treatment and warrants further studies.

Aged↗

PubMed2001

Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator.

Antibacterial peptides are active defense components of innate immunity. Several studies confirm their importance at epithelial surfaces as immediate barrier effectors in preventing infection. Here we report that early in Shigella spp. infections, expression of the antibacterial peptides LL-37 and human beta-defensin-1 is reduced or turned off. The downregulation is detected in biopsies from patients with bacillary dysenteries and in Shigella- infected cell cultures of epithelial and monocyte origin. This downregulation of immediate defense effectors might promote bacterial adherence and invasion into host epithelium and could be an important virulence parameter. Analyses of bacterial molecules causing the downregulation indicate Shigella plasmid DNA as one mediator.

Adult↗

PubMed2001

Cause-specific mortality in adults with unprovoked seizures. A population-based incidence cohort study.

PURPOSE: To determine the cause-specific mortality relative to that expected in a population-based incidence cohort of people with unprovoked seizures. METHODS: The cohort comprises 224 inhabitants of Iceland first diagnosed as suffering from unprovoked seizures during a 5-year period from 1960 to 1964. The expected number of deaths was calculated by multiplying person-years of observation within 5-year age categories for each year from diagnosis through 1995 by cause-specific and sex-specific national death rates for those aged 20 years and above. The standardized mortality ratio (SMR) and 95% confidence intervals (95% CI) were calculated. RESULTS: All-cause mortality was increased among men (SMR 2.25, 95% CI 1.56-3.14) but not women (SMR 0.79, 95% CI 0.38-1.46). Among men, there were 8 deaths from accidents, poisoning and violence observed versus 2.82 expected (SMR 2.84, 95% CI 1.22-5.59) and 4 deaths from suicide versus 0.69 expected (SMR 5.80, 95% CI 1.56-14.84). All-cause mortality for men was still elevated after restriction of analysis to those with seizures of unknown etiology (SMR 1.73, 95% CI 1.05-2.67) with the excess deaths attributable to suicide (SMR 5.26, 95% CI 1.06-15.38). Both males and females with remote symptomatic unprovoked seizures had an increase in all-cause mortality due to excess mortality from all cancers, cerebrovascular disease and accidents. CONCLUSION: When compared with the age-, time-period- and gender-specific mortality in the general population, there is excess mortality in men but not women. The increased mortality for men is partly attributable to excess mortality from accidents and suicides.

Accidents↗

PubMed2001

The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids.

A variant of the normal extracellular cysteine protease inhibitor cystatin C (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid angiopathy (HCCAA). It has been suggested that the mutation causes cellular entrapment of L68Q-cystatin C in vivo and that the variant protein is not secreted to extracellular fluids. In order to test this hypothesis, we used matrix-assisted laser desorption ionization time-of-flight mass spectrometry in an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in plasma and cerebrospinal fluid (CSF) of HCCAA-patients. Plasma from all five investigated HCCAA-patients contained both L68Q- and wildtype cystatin C. The presence of approximately equal amounts of cystatin C dimers and monomers was demonstrated in plasma from HCCAA-patients, whereas only monomers could be found in normal plasma. L68Q-wildtype-cystatin C heterodimers seem to be present in the dimeric cystatin C population. CSF from six HCCAA-patients also contained cystatin C-dimers and monomers, but the dimeric fraction was minute. CSF from control patients did not contain dimeric cystatin C. These results suggest that the milieu of L68Q-cystatin C is important for its stability and dimerization status and that certain milieus might hinder its further development into oligomers, amyloid fibrils and other precipitating aggregates.

Adult↗

PubMed2000

Copper, ceruloplasmin and superoxide dismutase (SOD) in amyotrophic lateral sclerosis.

In two previous studies we found copper dyshomeostasis in patients with Alzheimer's disease and in patients with Parkinson's disease. In this study, the levels of copper in plasma, of ceruloplasmin in serum, ceruloplasmin oxidative activity, ceruloplasmin specific oxidative activity (activity related to mass) as well as superoxide dismutase (SOD) activity in erythrocytes have been determined in 14 patients with amyotrophic lateral sclerosis and their healthy age- and gender-matched controls. Three of the patients had a familial form of the disease or were suspected of having it. The mean values of all parameters were found not to differ significantly between the patients and their controls (Student's t-test; P>0.05). By testing the equality of variances (F distribution) we found that the variances of individual results for ceruloplasmin specific oxidative activity and SOD activity differed significantly between the patients group and the controls group (P= 0.021 and P=0.003), but the individual results of these two activities were not correlated (P>0.05). We conclude that disturbances in ceruloplasmin specific oxidative activity and SOD activity could contribute to motor neurone death in amyotrophic lateral sclerosis, and since the two enzyme activities are not correlated it is uncertain which one is more closely related to the pathology of the disease.

Aged↗

PubMed2000

Risk of epilepsy in long-term survivors of surgery for aneurysmal subarachnoid hemorrhage: a population-based study in Iceland.

PURPOSE: Epilepsy is known to result from aneurysmal subarachnoid hemorrhage (SAH). There are no population-based estimates of the absolute risk or the duration for which this risk is elevated. We have conducted a population-based study in Iceland of the risk of epilepsy after a ruptured cerebral aneurysm to address these questions. METHODS: The index patients are all of the patients who presented with SAH caused by ruptured cerebral aneurysm in Iceland during an 11-year period (1958 to 1968) and survived more than 6 months. We determined the number of index patients who developed epilepsy. The observed number of cases of epilepsy was compared with that expected based on the incidence of epilepsy in Iceland. RESULTS: There were 44 index patients; 11 (25%) developed epilepsy, all within 4 years of the insult. Seven (70%) of 10 patients with acute symptomatic seizures (defined as seizures during the first 2 weeks after the hemorrhage) developed epilepsy (relative risk, 7.0; 95% confidence interval, 2.3-21.6). Epilepsy was more frequent in patients with severe neurological residua (48%) compared with patients without (20%) (relative risk, 2.5; 95% confidence interval, 0.9-6.3). CONCLUSIONS: The risk for epilepsy among survivors of SAH caused by ruptured cerebral aneurysm is substantially increased. Both acute symptomatic seizure and persistent neurological impairment are associated with a further increase in the risk of epilepsy.

Epilepsy↗

PubMed1999

Viral infection modulates expression of hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a granulomatous, inflammatory lung disease caused by inhalation of organic Ags, most commonly thermophilic actinomycetes that cause farmer's lung disease. The early response to Ag is an increase in neutrophils in the lung, whereas the late response is a typical Th1-type granulomatous disease. Many patients who develop disease report a recent viral respiratory infection. These studies were undertaken to determine whether viruses can augment the inflammatory responses in HP. C57BL/6 mice were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula (SR) for 3 consecutive days per wk for 3 wk. Some mice were exposed to SR at 2 wk after infection with respiratory syncytial virus (RSV), whereas others were exposed to SR after exposure to saline alone or to heat-inactivated RSV. SR-treated mice developed a typical, early neutrophil response and a late granulomatous inflammatory response. Up-regulation of IFN-gamma and IL-2 gene expression was also found during the late response. These responses were augmented by recent RSV infection but not by heat-inactivated RSV. Mice with a previous RSV infection also had a greater early neutrophil response to SR, with increased macrophage inflammatory protein-2 (MIP-2, murine equivalent of IL-8) release in bronchoalveolar lavage fluid. These studies suggest that viral infection can augment both the early and late inflammatory responses in HP.

Alveolitis, Extrinsic Allergic↗

PubMed1999

A phosphatidylcholine-specific phospholipase C regulates activation of p42/44 mitogen-activated protein kinases in lipopolysaccharide-stimulated human alveolar macrophages.

This study uses human alveolar macrophages to determine whether activation of a phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) is linked to activation of the p42/44 (ERK) kinases by LPS. LPS-induced ERK kinase activation was inhibited by tricyclodecan-9-yl xanthogenate (D609), a relatively specific inhibitor of PC-PLC. LPS also increased amounts of diacylglycerol (DAG), and this increase in DAG was inhibited by D609. LPS induction of DAG was, at least in part, derived from PC hydrolysis. Ceramide was also increased in LPS-treated alveolar macrophages, and this increase in ceramide was inhibited by D609. Addition of exogenous C2 ceramide or bacterial-derived sphingomyelinase to alveolar macrophages increased ERK kinase activity. LPS also activated PKC zeta, and this activation was inhibited by D609. LPS-activated PKC zeta phosphorylated MAP kinase kinase, the kinase directly upstream of the ERK kinases. LPS-induced cytokine production (RNA and protein) was also inhibited by D609. As an aggregate, these studies support the hypothesis that one way by which LPS activates the ERK kinases is via activation of PC-PLC and that activation of a PC-PLC is an important component of macrophage activation by LPS.

Bridged-Ring Compounds↗

PubMed1998

IL-12 modulates expression of hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a granulomatous, inflammatory lung disease caused by inhalation of organic Ags, most commonly thermophilic actinomycetes. Only a minority of individuals exposed to these Ags develops disease, suggesting that host factors are important for the expression of HP. We compared the expression of HP in a sensitive strain of mice, C57BL/6, and in a resistant strain of mice, DBA/2. They were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula (SR) or to saline alone for 3 consecutive days/week for 3 wk. After exposure to Ag, C57BL/6 mice, but not DBA/2 mice, developed granulomatous inflammation with an increase in lung index (lung weight). Both strains had similar amounts of Ag delivered to the lungs after intranasal installation, as determined with 14C-labeled Ag. Both also had similar increases in total bronchoalveolar cells after Ag exposure, but the C57BL/6 mice had more lymphocytes. Compared with the resistant strain, the sensitive strain had a significantly greater Ag-induced increase in IL-12 and IFN-gamma gene expression. DBA/2 mice resembled sensitive, C57BL/6 mice if they received IL-12 augmentation therapy at the time of Ag exposure. These findings were not limited to lung, since both unstimulated and SR-stimulated spleen cells from C57BL/6 mice released significantly more IL-12 than cells from DBA/2 mice. However, spleen cells from DBA/2 mice made more IFN-gamma when exposed to IL-12, than cells from C57BL/6 mice. These results suggest that the IL-12 response to Ag may modulate in part the expression of HP.

Adjuvants, Immunologic↗

PubMed1998

Hereditary cystatin C amyloid angiopathy: monitoring the presence of the Leu-68-->Gln cystatin C variant in cerebrospinal fluids and monocyte cultures by MS.

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant condition in which the patients suffer at an early age from repeated cerebral haemorrhages. The development of HCCAA is directly linked to a Leu-68-->Gln (L68Q) mutation in the cystatin C protein sequence. The concentration of cystatin C in cerebrospinal fluid (CSF) of HCCAA patients is markedly diminished and cultivated monocytes from affected individuals accumulate cystatin C. The goal of this work was to characterize cystatin C isolated from CSF and monocyte cultures originating from healthy persons and HCCAA patients with respect to the L68Q mutation. Cystatin C was isolated by carboxymethylpapain affinity chromatography. Proteins from CSF and monocyte cultures that bound specifically to the carboxymethylated papain column were resolved by reverse-phase HPLC chromatography and tryptic peptides were subsequently analysed by matrix-assisted laser desorption ionization MS. No evidence for mutated cystatin C protein was found in CSF samples from healthy subjects or HCCAA patients, but approx. 60% of the protein was found to be hydroxylated on Pro-3. No evidence was found for secretion of mutated cystatin C from HCCAA monocytes. However, we obtained evidence for the presence of mutated cystatin C in HCCAA monocytes. These results support the conclusion that the mutated cystatin C is retained in association with the monocytes and not secreted. An increased intracellular concentration would presumably promote the aggregation and denaturation of the mutated cystatin C, leading to the formation of amyloid fibrils and cell death.

Amino Acid Sequence↗

PubMed1998

Pregnancies of women with epilepsy: a population-based study in Iceland.

PURPOSE: Women with epilepsy who become pregnant are commonly considered to be at high risk for complications during pregnancy or delivery. The offspring are also considered to have increased risk of perinatal mortality, congenital malformations, and maturational delay. Because few of these studies are population based, potential bias exists because of selection. METHODS: We performed a historical population-based cohort study in Iceland to determine the prevalence of epilepsy among pregnant women, to identify pregnancy and delivery complications in women with epilepsy, and to determine the outcome of their pregnancies as compared with that in the general population of Iceland. We identified all women with active epilepsy who gave birth during a 19-year period in Iceland. RESULTS: In this population, 3.3 in 1,000 pregnancies involve mothers with active epilepsy. The frequency of adverse events (AE) during pregnancy in the women with epilepsy is similar to that observed among all live births in the population, but cesarean section was performed twice as frequently as in the general population. Perinatal mortality rate and mean birth weight are not significantly different in the offspring of women with epilepsy as compared with rest of the population. The risk of major congenital malformations (MGM) is increased 2.7-fold over that expected when a mother is treated with antiepileptic drugs (AEDs) during a pregnancy. CONCLUSIONS: Our study indicates that the rate of complications of pregnancy in mothers with active epilepsy is low and similar to that of the general population with epilepsy. Use of AEDs by the mother during pregnancy significantly increases the risk of MGM in the offspring.

Abnormalities, Drug-Induced↗

PubMed1998

Long-term survival of people with unprovoked seizures: a population-based study.

PURPOSE: Few population-based studies of long-term survival in people with seizures or epilepsy have been made. METHODS: Between January 1, 1960 and December 31, 1964, we identified 224 incidence cases of unprovoked seizures in Iceland and determined survivorship status and date of death for the cases as of January 1, 1996. We compared survivorship with that expected based on data from age-/sex-specific life tables from the country for 1961-1990 and calculated the standardized mortality ratio (SMR). RESULTS: By 30 years after diagnosis, there were 45 deaths among patients with unprovoked seizures as compared with an expected 28 deaths [standardized mortality ratio (SMR) 1.6; 95% confidence interval (CI) 1.2-2.2]. Patients with unprovoked seizures of unknown etiology did not have a significant increase in mortality overall (SMR 1.3, 95% CI 0.8-1.9) or in any time interval. For patients with remote symptomatic unprovoked seizures, mortality was increased (SMR 2.3, 95% CI 1.4-3.5). This increase was attributable to excess mortality for the first 15 years after diagnosis (SMR 4.1, 95% CI 2.4-6.6), and SMR was not different after that time. CONCLUSIONS: Survivorship was decreased for the population of patients with unprovoked seizures. The increased mortality was primarily due to excess mortality in patients with remote symptomatic seizures, occurring in the first 15 years after diagnosis. Overall mortality for idiopathic unprovoked seizures was not significantly increased.

Adult↗

PubMed1998

Changes in PKC isoforms in human alveolar macrophages compared with blood monocytes.

Alveolar macrophages play an important role in host defense and in other types of inflammatory processes in the lung. These cells exhibit many alterations in function compared with their precursor cells, blood monocytes. To evaluate a potential mechanism for these differences in function, we evaluated expression of protein kinase C (PKC) isoforms. We found an increase in Ca2+-dependent PKC isoforms in monocytes compared with alveolar macrophages. We also found differential expression of the Ca2+-independent isoforms in alveolar macrophages compared with monocytes. One consequence of the activation of PKC can be increased expression of mitogen-activated protein (MAP) kinase pathways. Therefore, we also evaluated activation of the MAP kinase extracellular signal-regulated kinase (ERK) 2 by the phorbol ester phorbol 12-myristate 13-acetate (PMA). PMA activated ERK2 kinase in both alveolar macrophages and monocytes; however, monocytes consistently showed a significantly greater activation of ERK2 kinase by PMA compared with alveolar macrophages. Another known consequence of the activation of PKC and subsequent activation of ERK kinase is activation of the transcription factor activator protein-1 (AP-1). We evaluated the activation of AP-1 by PMA in both monocytes and macrophages. We found very little detectable activation of AP-1, as assessed in a gel shift assay, in alveolar macrophages, whereas monocytes showed a substantial activation of AP-1 by PMA. These studies show that the differential expression of PKC isoforms in alveolar macrophages and blood monocytes is associated with important functional alterations in the cells.

Bronchoalveolar Lavage Fluid↗

PubMed1998

Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice.

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by granuloma formation. We recently showed that interferon-gamma (IFN-gamma) is essential for inflammation and granuloma formation in HP. Interleukin-10 (IL-10) counteracts many of the biologic effects of IFN-gamma, suggesting that IL-10 modulates inflammation and granuloma formation in HP. We compared the expression of HP in C57BL/6 mice that lack IL-10 (IL-10 knockout [KO]) with that in wild-type (WT) littermates. IL-10 KO and WT mice were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula or to saline alone for 3 wk. The IL-10 KO mice had higher cell counts in their bronchoalveolar lavage fluid (2.85 +/- 0. 43 x 10(6)) than did WT mice (1.4 +/- 0.3 x 10(6)/ml; P < 0.03), with a more prominent neutrophil response. They also had greater inflammation after antigen exposure than did the WT mice (P < 0. 0001). There was increased upregulation of IFN-gamma, IL-1, and tumor necrosis factor-alpha (TNF-alpha) mRNAs in the lungs of IL-10 KO mice. Adenovirus-mediated gene transfer of IL-10 to the liver of IL-10 KO mice reduced the inflammation from that seen in WT mice. These studies show that IL-10 has important anti-inflammatory properties in HP, and that lack of this cytokine leads to a more severe granulomatous inflammatory response.

Adenoviridae↗

PubMed1998

Fertility in patients with epilepsy: a population-based study.

OBJECTIVE: Several studies have suggested that people with epilepsy have altered fertility, but comparison groups have been imperfect. METHOD: A retrospective cohort study of all live births to 209 incident patients with epilepsy in Iceland from 1960 to 1964 and live births to 418 age- (to the closest day of birth) and gender-matched residents without epilepsy. RESULTS: Incident patients with epilepsy had an average of 2.0 children; the controls also had an average of 2.0 children. When people with idiopathic/cryptogenic epilepsy were compared with controls, there was no difference in number of children or number of partners overall, nor were there differences when stratified by seizure type or age at diagnosis. There was a deficit in the number of children among patients with remote symptomatic epilepsy. This was attributed to a reduced number of offspring of patients with mental retardation (MR) or cerebral palsy (CP) when compared with their controls. CONCLUSION: There is no evidence of altered fertility among people with idiopathic/cryptogenic epilepsy or remote symptomatic epilepsy (other than MR or CP) within this population-based incidence cohort.

Adolescent↗

PubMed1997

Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis.

Farmers lung disease is a common form of hypersensitivity pneumonitis (HP) and is characterized by inflammation and granuloma formation in the lung. Interferon-gamma is important for the expression of granulomatous diseases caused by infectious agents; however, the role this mediator in regulating expression of the granulomatous response to inhaled antigen is not known. To evaluate this, we compared the response to inhaled antigen of mice that do not express the gene coding for interferon-gamma (GKO) with that of their normal littermates (WT). GKO and WT mice on a BALB/c background were exposed to 150 microg of the thermophilic bacteria Saccharopolyspora rectivirgula or saline alone, for three consecutive days a week, for 3 wk. After exposure to antigen, WT mice developed a marked granulomatous inflammation associated with an increase in lung weight and numbers of cells in bronchoalveolar lavage fluid (BAL). Although GKO mice also exhibited an increase in lung weight and numbers of cells in BAL fluid, they developed minimal inflammation and no granulomas after a similar exposure to antigen. To further evaluate if the lack of a response to antigen in GKO mice was due to lack of IFN-gamma, we replaced this mediator via intraperitoneal injections. When given replacement IFN-gamma, the GKO mice developed granulomatous inflammation in the lung. These studies show that IFN-gamma is essential for the expression of hypersensitivity pneumonitis.

Alveolitis, Extrinsic Allergic↗