Influence of human T lymphotrophic virus type I on cryptogenic fibrosing alveolitis - HTLV-I associated fibrosing alveolitis: proposal of a new clinical entity.

Human T lymphotrophic virus type-I (HTLV-I), a human retrovirus, infects CD4+ lymphocytes and is thought to modify their function; a possible association with pulmonary diseases has also been suggested. However, little is known about the influence of HTLV-I on cryptogenic fibrosing alveolitis (CFA), a chronic inflammatory interstitial lung disease of unknown aetiology. In order to clarify the influence of HTLV-I infection on CFA, 72 CFA patients with and without HTLV-I infection were examined. HTLV-I positive CFA patients were likely to have larger affected areas and to show traction bronchiectasis with honeycombing change. An imbalance of matrix metalloproteinases and tissue inhibitor of metalloproteinases were also observed in the BALF of HTLV-I positive CFA patients. CD3+/CD25+ lymphocyte percentage was significantly higher in the BALF of HTLV-I positive patients compared to negative patients. MIP-1alpha, IP-10 and sICAM levels in BALF were also significantly higher in HTLV-I positive patients than in negative patients. The levels of MCP-1 and IL-8 were not significantly different. In HTLV-I positive patients, the MIP-1alpha and IP-10 levels showed a significant positive correlation with percentage of CD3+/CD25 lymphocytes. HTLV-I positive CFA patients showed a larger lesion than negative patients and exhibited increased levels of certain cytokines that correlated with activated T cells in the BALF. We suggest that HTLV-I infection may contribute to the development of CFA via activation of T cells. We also propose that these features should be taken into consideration in the treatment of CFA in HTLV-I infected individuals.

Enhanced inhibition of lymphocyte activation by Mycobacterium avium complex in human T lymphotrophic virus type I carriers.

BACKGROUND: We have previously reported that disseminated pulmonary Mycobacterium avium complex (MAC) infection is more common in human T lymphotrophic virus type I (HTLV-I) carriers than in non-carriers. However, the reason for this remains unclear. It has been shown that glycopeptidelipid (GPL), one of the lipid components of the cell envelope of MAC, is able to reduce the lymphocyte blastogenic response to mitogens. The purpose of this study was to clarify whether or not the inhibitory effect of GPL differs between HTLV-I carriers and non-carriers. METHODS: Peripheral blood lymphocytes were obtained from 29 patients who had recovered from pulmonary MAC infection (10 of whom also had HTLV-I infection) and the lymphocyte counts and T cell subpopulations of the peripheral blood lymphocytes in HTLV-I carriers and non-carriers were compared. The inhibitory effect of GPL on the lymphocyte blastogenic response to phytohaemagglutinin (PHA) was tested in these 29 cases and in 15 healthy controls who had never suffered from MAC (seven of whom also had HTLV-I infection). All HTLV-I positive cases were carriers. RESULTS: There was no significant difference in the numbers or subset proportions of T cells between HTLV-I carriers and non-carriers. Lymphocyte activation by PHA was significantly inhibited by GPL in MAC positive and negative HTLV-I carriers compared with MAC negative non-carriers and MAC negative healthy controls (p<0.001). CONCLUSIONS: We suggest that MAC infection leads to strong inhibition of lymphocyte activation in HTLV-I carriers. This may account, in part, for the severity of pulmonary MAC infection in HTLV-I carriers.

Expression of vascular endothelial growth factor in pulmonary aspergilloma.

OBJECTIVE: Vascular endothelial growth factor (VEGF), a cytokine associated with malignant neoplasms, is increased in a number of inflammatory and infectious disorders. But little is known about VEGF in pulmonary aspergilloma (PA). In order to clarify the predictive value of VEGF in PA, we examined serum VEGF levels in PA patients as well as expression of VEGF in the PA lesion. Patients Twenty-one patients with PA (6 with hemoptysis and the rest without hemoptysis) were investigated. METHODS: In all patients, serum VEGF levels were measured by enzyme-linked immunosorbent assay. We examined the statistical correlations of serum VEGF levels with the ratio of affected area to total lung volume and VEGF with PaO2 levels. In patients with hemoptysis, we measured the serum VEGF levels three months after the initiation of therapy. We examined the expression of VEGF in the resected lung tissue of 4 patients with PA using immunohistochemistry. RESULTS: Serum VEGF levels showed a significant positive correlation with the ratio of affected to total lung area and a significant negative correlation with PaO2 levels. Serum VEGF levels in patients with hemoptysis were significantly higher than in those without hemoptysis. The serum levels of VEGF in patients with hemoptysis decreased significantly in parallel with the alleviation of hemoptysis. Immunohistochemical staining demonstrated the expression of VEGF in alveolar macrophages in the lesion of PA patients. CONCLUSION: We suggest that VEGF can be used as a serum marker to determine the extent of the lesion, hypoxia and hemoptysis in PA.

Clinical investigation of pulmonary Mycobacterium avium complex infection in human T lymphotrophic virus type I carriers.

BACKGROUND: Little is known about pulmonary Mycobacterium avium complex (MAC) infection in human T lymphotrophic virus type I (HTLV-I) carriers. A study was undertaken to investigate and clarify the characteristics of pulmonary MAC infection in these subjects. METHODS: Twenty nine patients with pulmonary MAC infection without any underlying pulmonary disorder were investigated. The clinical features and radiographic appearance of HTLV-I carriers and non-carriers were compared and the bronchoalveolar lavage (BAL) fluid of these 29 patients and eight normal female control subjects was analysed. RESULTS: The prevalence of the HTLV-I carrier state in patients with pulmonary MAC infection was 34.5% (10/29) compared with 16.7% (529/3169) among all patients admitted to our department between 1994 and 1998 (odds ratio (OR) 2.63, 95% confidence interval (CI) 1.21 to 5.68). The HTLV-I carriers were all women and all had clinical symptoms, but they did not show systemic dissemination. Peripheral multifocal bronchiectasis with nodular shadowing was seen frequently on the chest computed tomographic (CT) scans of HTLV-I carriers. The area of the pulmonary lesions was more extensive than in non-carriers (p<0.05). White blood cell (WBC) counts and C reactive protein (CRP) levels on admission were significantly lower in HTLV-I carriers than in non-carriers (WBC: difference (D) = 1565/microl, 95% CI -68.9 to 3198.4/microl; CRP: D = 1.8 mg/dl, 95% CI -0.35 to 3.89 mg/dl). The concentrations of neutrophil elastase (NE) and interleukin (IL)-8 in BAL fluid were significantly higher in HTLV-I carriers than in non-carriers (NE: D = 1342 microg/l, 95% CI 704 to 1980.3 microg/l; IL-8: D = 304.5 pg/ml, 95% CI 89.7 to 519. 4 pg/ml). CONCLUSIONS: Pulmonary MAC infection causes more diffuse and widespread lesions in HTLV-I carriers than in non-carriers.

Bronchiectasis with myeloperoxidase antineutrophil cytoplasmic antibody and bactericidal/permeability-increasing protein antineutrophil cytoplasmic antibody.

A 56-year-old woman was hospitalized for recurrent hemoptysis. She had been suffering from bronchiectasis for 4 years. Pseudomonas aeruginosa was persistently detected in her sputum. Serum was positive for Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) and bactericidal/permeability-increasing protein antineutrophil cytoplasmic antibody (BPI-ANCA). She underwent lung resection. Histopathologically, the resected lung showed bronchiectasis with pulmonary fibrosis but did not show vasculitis. Her serum became negative for the ANCAs after the operation. To date, she has no recurrence of hemoptysis. We discuss this case of bronchiectasis with MPO-ANCA and BPI-ANCA and suggest a possible role for ANCAs in chronic airway infection.

Two cases of idiopathic CD4+ T-lymphocytopenia in elderly patients.

We present 2 cases of idiopathic CD4+ T-lymphocytopenia (ICL) in elderly patients. Case 1, a 73-year-old man, with pneumonia had received several antibiotics with unsuccessful results at another hospital. On admission, his CD4+ T-lymphocyte count was 109/microl and Pneumocystis carinii was detected by bronchoalveolar lavage fluid staining. No evidence of human immunodeficiency virus (HIV) infection was found. Despite therapy, the patient died of respiratory failure. Case 2, a 72-year-old man, contracted severe pneumonia, and Hemophillus influenzae was believed to be the pathogen. On admission, his CD4+ T-lymphocyte count was 238/microl. No evidence of HIV infection was found. He received antibiotics and improved successfully. We suggest that ICL may currently be incubating in a number of elderly pneumonia patients.

An autopsy case of peripheral neuroepithelioma in posterior mediastinum with p53 point mutation.

An 18-year old male was admitted to our hospital complaining of back pain. His chest computed tomography showed a tumor in the posterior mediastinum. Open biopsy was performed, and a diagnosis of peripheral neuroepithelioma was made. No genetic abnormalities were detected in the DNA obtained from the biopsy specimen. He received chemotherapy and radiation several times. These treatment regimens were effective, but he relapsed 14 months later and died of respiratory failure due to tumor growth. Autopsy examination revealed a large tumor which occupied almost the entire right thoracic cavity, but there was no evidence of metastasis to other organs. Chromosomal translocation t(14;17) (q24;p12.2) and point mutation of exon 5 of the p53 gene were detected.

[Advanced stage of giant axonal neuropathy].

A woman has appeared normal during her neonatal and childhood period except for a short stature. Her parents were healthy and non-consanguineous. At the age of 8, she noticed difficulty in climbing stairs and had tendency to fall. In her 13th year, she developed marked scoliosis and genu valgum. Physical examination at 14 years of age revealed a gentle and shy child of short stature with brown-black kinky hair. Neurological examinations revealed progressive mental retardation, optic nerve atrophy, moderate and coarse nystagmus on lateral and vertical gaze, atrophic tongue with fasciculations, slow and scanning speech, distal muscular weaknesses with diffuse atrophies in the four extremities and sensory deficiencies in all modalities with a glove-stocking type distribution. At the age of 15, she was unable to walk without a wheelchair. During the course she showed slowly progressive muscular weakness, ataxia and decreasing sensation especially in the lower extremities. She died of infection of the respiratory and urinary tracts at the age of 25. Pathologically the abnormalities in the biopsied and autopsied sural nerve were characterized by an advanced stage of nerve fiber degeneration without giant axons. The phrenic nerve obtained at autopsy at 1 to 10 cm from axon terminal revealed the presence of several large focal axonal swelling of 15-20 microns in diameter. On the other hand, sections of the phrenic nerve at 15 cm from axon terminal displayed a mild to moderate reduction in the number of myelinated fibers without giant axons. The difference of pathological findings among these specimens seems to depend on the time as well as the site of the examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased accumulation of iodine-123-IMP in the pulmonary inflammatory lesion surrounding a lung cancer.

In a patient with primary lung cancer, increased accumulation of I-123-IMP was observed in a pulmonary inflammatory lesion surrounding a lung cancer which was delineated as a photon deficient area. Ga-67-citrate uptake was observed in both the inflammatory and cancerous areas. These findings suggest that I-123-IMP may have the potential to accumulate differently in a variety of pathological conditions of the lung and thus may be a clinically useful lung imaging agent.

Juvenile secretory carcinoma and juvenile papillomatosis.

Two cases of juvenile secretory carcinoma associated with juvenile papillomatosis are reported. One patient's disease was initially diagnosed at the age of 13 and she died 12 years later with extensive metastases. The contralateral breast at autopsy showed findings indicative of juvenile papillomatosis. The second case is that of an 18-year-old girl who had multiple juvenile secretory carcinomas in the left breast associated with juvenile papillomatosis.