Cyclooxygenase-2 expression during allergic inflammation in guinea-pig lungs

Prostaglandins and thromboxanes are important modulators of airway physiology. The synthesis of these mediators depends on two isoforms of cyclooxygenase (COX), constitutive COX-1 and inducible COX-2. COX-2 expression has been observed in various inflammatory diseases, but not all aspects of the expression and the role of COX-2 in conditions of allergic inflammation such as asthma are clear. In the present study, we examined the 72-h kinetics of the expression of COX-isoform mRNA in ovalbumin-sensitized and -challenged guinea-pig lungs. The sensitized animals showed a robust and transient induction of COX-2 mRNA expression within 1 h after ovalbumin challenge, whereas their COX-1 mRNA levels remained unchanged. Upregulation of the level and activity of COX-2 protein followed the induction of COX-2 mRNA. Lung slices harvested from ovalbumin-challenged animals released more prostaglandin D(2) and prostaglandin E(2) spontaneously or in response to A23187 (10 microM) ex vivo than did those from unchallenged animals. This response was significantly blocked by the COX-2 selective inhibitors, NS-398 and JTE-522. In vivo administration of NS-398 significantly inhibited the accumulation of eosinophils and neutrophils in the lungs. In conclusion, de novo COX-2 expression during allergic inflammation modifies prostanoid synthesis in the lung and airway pathophysiology.     

Correlation of urine type I collagen-cross-linked N telopeptide levels with bone scintigraphic results in prostate cancer patients

The diagnostic potential of a new bone resorption marker, type I collagen-cross-linked N telopeptide (NTx), for bone metastasis of prostate cancer was evaluated. Ninty-one prostate cancer patients underwent bone scintigraphy, and urine NTx/creatinine (NTx/Cr) was measured. Urine NTx/Cr levels were compared with bone scintigraphic results. Urine NTx/Cr levels in the bone metastasis-positive group (n = 47) were 92.9 +/- 105.1 nmol/L of bone collagen, which is equivalent to per millimole of urinary creatinine (nmol/L BCE/mmol/L Cr), significantly higher than the level of the bone metastasis-negative group (n = 44) (59.0 +/- 41.6 nmol/L BCE/mmol/L Cr). When patients were classified by the extent of disease grade (EOD grade) nomenclature, the urine NTx/Cr level of the EOD (4+) group was 209.5 +/- 186.5 nmol/L BCE/mmol/L Cr. This level was significantly higher than those of the EOD (-) group (59.0 +/- 41.6 nmol/L BCE/mmol/L Cr), EOD (1+) group (59.0 +/- 47.8 nmol/L BCE/mmol/L Cr), and EOD (2+) group (81.1 +/- 41.3 nmol/L BCE/mmol/L Cr). However, no significant difference was observed between the EOD (-) and EOD (1+) groups. The mean change in urine NTx/Cr level 3 to 17 months after the first bone scintigraphy and urine NTx/Cr examination in the bone metastasis-progression group (n = 8) was 11.0 +/- 31.2 nmol/L BCE/mmol/L Cr, significantly higher than that in the bone metastasis-regression group (n = 15) (-26.8 +/- 40.7 nmol/L BCE/mmol/L Cr). In conclusion, urine NTx /Cr can be measured noninvasively and reflects the state of bone metastasis. However, the sensitivity of urine NTx/Cr is not as high as that of bone scintigraphy. Therefore, it may provide an auxiliary diagnostic index for bone scintigraphy.     

A case of hypersensitivity pneumonitis caused by Humicola fuscoatra

A 51-year-old housewife with hypersensitivity pneumonitis caused by Humicola fuscoatra is reported. The diagnosis was made by an inhalation challenge with H. fuscoatra antigen. She was admitted for diagnosis and treatment of a fever and productive cough. Auscultation of her lungs revealed inspiratory fine crackles. Her chest CT showed diffuse miliary nodules in a centri-lobular distribution with patchy ground glass opacities. Findings of transbronchial lung biopsy and BAL fluid were compatible with a hypersensitivity pneumonitis. Her symptoms worsened on returning home, which suggested the existence of some aetiological agent in the subject's house. H. fuscoatra, Penicillium decumbens and Aspergillus versicolor were isolated from a number of rooms. High titres of serum anti H. fuscoatra, P. decumbens and A. versicolor were detected. Inhalation challenge tests with both P. decumbens and A. versicolor antigen were negative, in contrast to that with H. fuscoatra which was positive. Based on these results, we advised the patient to cleanse her entire house. Since cleaning, her symptoms have not worsened upon returning home. This is the first report of hypersensitivity pneumonitis caused by H. fuscoatra antigen.     

Fas ligand expressing mononuclear cells around intrahepatic bile ducts co‐express CD68 in primary biliary cirrhosis

Abstract: Aims/Background: Apoptosis, including the Fas system, has been implicated in progressive bile duct loss in primary biliary cirrhosis (PBC). In this study, we attempted to analyze Fas ligand (FasL) expressing mononuclear cells infiltrating in the portal tracts of PBC. Methods: We immunohistochemically assessed co‐expression of leukocyte markers and FasL on infiltrating mononuclear cells in 18 patients with PBC. Twenty‐five patients with chronic hepatitis C (CH‐C) were used as controls. Results: In PBC, FasL expressing cells were scattered in the portal tracts, and some were accentuated around the damaged bile ducts. In addition, these cells co‐expressed CD68 (71%), a marker of monocytes, but not UCHL‐1, CD3 and CD57, markers of activated T cells and natural killer cells. By contrast, in CH‐C, the biliocentric pattern of FasL expression was not evident, and about half of FasL expressing cells (42–56%) co‐expressed UCHL‐1, CD3 or CD57. CD14, a receptor for bacterial products such as lipopolysaccharides, was also detected on a proportion of FasL expressing mononuclear cells around the damaged bile ducts in PBC. Conclusion: The results suggest that in PBC, FasL expressing CD68+ monocytes are at least partly involved in apoptotic bile duct loss mediated by the Fas system, and a surface molecule, CD14, participates in this process.     

Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis

Aim: In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3-positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians. Methods: We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16-79 years). Results: Forty-seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%). Conclusion: In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre-existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without.     

Long-term effectiveness of an inpatient pulmonary rehabilitation program for elderly COPD patients: comparison between young-elderly and old-elderly groups

OBJECTIVE: To evaluate the long-term effects of pulmonary rehabilitation in elderly COPD patients, we monitored patients for 1 year after they completed a 2-week inpatient pulmonary rehabilitation program. We also compared the effects of pulmonary rehabilitation on young-elderly (age 65-74 years) and old-elderly (age 75 years or over) COPD patients. METHODOLOGY: Fifty-nine elderly COPD patients (mean age 72.8 years) were studied. They underwent a comprehensive 2-week inpatient pulmonary rehabilitation program incorporating 10 exercise sessions, each of which included endurance training of the lower extremities, peripheral muscle conditioning training of the upper and lower extremities, and stretching, along with various education sessions. The effects of pulmonary rehabilitation were evaluated at 3, 6, and 12 months after completion of the program. RESULTS: Overall, patient health-related quality of life (HRQoL) as assessed by a QoL scale, and dyspnoea as assessed by an oxygen cost diagram, improved significantly over the 12-month period. Exercise capacity assessed by a 6-min walking distance test (6MWD) was similarly significantly improved. However, there was some fall-off in terms of the distance walked 12 months after pulmonary rehabilitation. The improvements in exercise capacity, dyspnoea, and HRQoL did not differ between the two groups, with the exception that the 6MWD (P < 0.01) and the QoL scale (P < 0.05) at 3 months post-pulmonary rehabilitation were significantly higher in the old-elderly group. CONCLUSIONS: Pulmonary rehabilitation is an effective treatment in terms of improving dyspnoea, exercise capacity and HRQoL in elderly COPD patients, and the benefits are almost comparable for young-elderly and old-elderly patients.     

Pancreatic arteriovenous malformation with pancreatitis involving a pancreatico-venous fistula

An arteriovenous malformation of the pancreas is a very rare disease, but its presentation is distinct and unique. In this report, we describe a patient who presented with this malformation which was localized in the tail of pancreas and demonstrated by abnormal angiography findings. The patient was a 60-year-old male with severe left hypochondralgia. Angiography revealed an increased blood volume in the tail of the pancreas with arteriovenous shunting. Secondary pancreatitis caused by the arteriovenous malformation was suspected by abnormal laboratory data, and confirmed by histology from the resected tail of the pancreas. This is a very rare report in which pancreatic arteriovenous malformation involving a pancreaticovenous fistula was confirmed by endoscopic retrograde cholangiopancreatography (ERCP).     

Cloning of serum RNA associated with hepatitis C infection suggesting heterogeneity of the agent(s) responsible for the infection

Fifty-six lambda gt11-random-primed-cDNA recombinants of which translation products react with antibodies in the serum drawn from patients with hepatitis C (blood-borne non-A, non-B hepatitis) were cloned from serum pooled from donors presumably infected with hepatitis C. The specificity of these clones for hepaitits C infection was determined using 3 test panels. Of these 29 clones were determined to be specific for Japanese hepatitis C infection. However one of the 29 clones was positive for 1 out of 5 normals in an American test panel while 12 clones were positive for the American panel as well. The remaining 28 clones reacted well with serum from transfusion associated chronic hepatitis C comparing to the sporadic cases in the Japanese panel. When they were tested with normal donors, another clone reacted with a distinct donor group with which the other clones did not react. These results may suggest the presence of heterogeneity in Japanese hepatitis C.