Comparison of sensitivity of lung nodule detection between radiologists and technologists on low-dose CT lung cancer screening images.

OBJECTIVES: The objective of this study was to compare the sensitivity of detection of lung nodules on low-dose screening CT images between radiologists and technologists. METHODS: 11 radiologists and 10 technologists read the low-dose screening CT images of 78 subjects. On images with a slice thickness of 5 mm, there were 60 lung nodules that were ≥5 mm in diameter: 26 nodules with pure ground-glass opacity (GGO), 7 nodules with mixed ground-glass opacity (GGO with a solid component) and 27 solid nodules. On images with a slice thickness of 2 mm, 69 lung nodules were ≥5 mm in diameter: 35 pure GGOs, 7 mixed GGOs and 27 solid nodules. The 21 observers read screening CT images of 5-mm slice thickness at first; then, 6 months later, they read screening CT images of 2-mm slice thickness from the 78 subjects. RESULTS: The differences in the mean sensitivities of detection of the pure GGOs, mixed GGOs and solid nodules between radiologists and technologists were not statistically significant, except for the case of solid nodules; the p-values of the differences for pure GGOs, mixed GGOs and solid nodules on the CT images with 5-mm slice thickness were 0.095, 0.461 and 0.005, respectively, and the corresponding p-values on CT images of 2-mm slice thickness were 0.971, 0.722 and 0.0037, respectively. CONCLUSION: Well-trained technologists may contribute to the detection of pure and mixed GGOs ≥5 mm in diameter on low-dose screening CT images.

Detectability of peripheral lung cancer on chest radiographs: effect of the size, location and extent of ground-glass opacity.

The purpose of this study was to evaluate the effect of the size and location of lung tumour and the extent of ground-glass opacity (GGO) on thin-section CT for the detection of peripheral lung cancer on chest radiographs. 100 posteroanterior chest radiographs of peripheral lung cancer 20 mm in diameter or smaller were reviewed retrospectively by two chest radiologists individually. Lung cancer was detectable on chest radiographs in 51 (51%) cases. However, in six cases, the tumour was recognized not as a nodular opacity but as a subpleural linear or localized hazy opacity. The median size of detectable lung cancer (17 mm) was larger than that of undetectable lung cancer (14 mm; p<0.001). The frequency of tumours with extent of GGO less than 70% was 94% in detectable cases and 59% in undetectable cases (p<0.001). The frequency of tumours located in unobscured lung was 94% in detectable cases and 59% in undetectable cases (p<0.001). The detectability of peripheral lung cancer on chest radiographs is influenced by tumour size, location and extent of GGO seen on thin-section CT. It should also be noted that some tumours may not be recognized as a nodular opacity even if they are detectable.

Regulation of acrosome reaction of fowl spermatozoa: evidence for the involvement of protein kinase C and protein phosphatase-type 1 and/or -type 2A.

The signal transduction pathways involved in the regulation of the acrosome reaction and motility of fowl spermatozoa were investigated. The motility and acrosomal integrity of fowl spermatozoa in TES/NaCl buffer, with or without homogenised inner perivitelline layers (IPVL), prepared from laid fowl eggs, was almost negligible at 40 degrees C. In the presence of 2 mmol CaCl(2)/l at 40 degrees C, motility became vigorous and the acrosome reaction was stimulated when IPVL was added. In the absence of Ca(2+), motility was stimulated by the addition of calyculin A and okadaic acid, both specific inhibitors of protein phosphatase-type 1 (PP1) and -type 2A (PP2A), but Okadaic acid, which is a weaker inhibitor of PP1, did not completely restore motility at 40 degrees C. However, the acrosome reaction was significantly and equally stimulated in a dose-dependent manner by both inhibitors in the range of 10-1000 nmol/l, when spermatozoa were incubated with IPVL but without Ca(2+). These inhibitors did not stimulate the acrosome reaction in the absence of IPVL. The vigorous motility of spermatozoa, stimulated by the addition of Ca(2+), was reduced gradually as the concentrations of SC-9, a selective activator of protein kinase C (PKC), were increased and a similar SC-9-induced inhibition was observed in the acrosome reaction in the presence of Ca(2+) and IPVL. These results confirm that IPVL is necessary for the activation of the acrosome reaction in fowl spermatozoa and that Ca(2+) plays an important role in the stimulation of motility and acrosomal exocytosis. Furthermore, it appears that the intracellular molecular mechanisms for the regulation of acrosome reaction of fowl spermatozoa are different from those for the restoration of motility, i.e., protein dephosporylation involving PP1 and/or PP2A in the former, and PP1 alone in the latter case. In addition, the activation of PKC may contribute to a decrease in the flagellar movement and acrosome reaction of fowl spermatozoa.

Effects of calpain and Rho-kinase inhibitors on the acrosome reaction and motility of fowl spermatozoa in vitro.

At the avian body temperature of 40 degrees C, intact fowl spermatozoa require Ca(2+) for the initiation of motility and a combination of both Ca(2+) and homogenized inner perivitelline layer (IPVL) together to induce the acrosome reaction. Within the range of 1-100 micromol/l, neither PD 150606 (a Ca(2+)-dependent calpain inhibitor) nor Y-27632 (an inhibitor of Ca(2+)-dependent Rho-kinase) were able to inhibit the acrosome reaction induced by the presence of Ca(2+) and IPVL. However, PD 150606, although not Y-27632, was able to inhibit sperm motility initiated by Ca(2+), as well as motility initiated by calyculin A -- a specific inhibitor of protein phosphatases, which also initiates sperm motility at 40 degrees C. The addition of PD 150606 did not reduce the ATP concentrations of intact spermatozoa, nor the motility of demembranated spermatozoa. Immunoblot analysis of sperm extract using a polyclonal antibody against calpain 12 revealed a cross-reacting protein of approximately 80 kDa. These results suggest that Rho-kinase is not involved in the regulation of the acrosome reaction or of motility in fowl spermatozoa. In contrast, calpain appears to be involved in the regulation of flagellar movement, but not izn that of the acrosome reaction. Furthermore, it seems that endogenous calpain is present in the cytoplasmic matrix and/or the plasma membrane, but not retained in the axoneme and/or accessory cytoskeletal components.

Coexistence of lung cancer and tuberculoma in the same lesion: demonstration by high resolution and contrast-enhanced dynamic CT.

We report a case of coexistence of lung cancer and tuberculoma in the same lesion. The component parts of lung cancer and tuberculoma were identified on the basis of morphology on high-resolution CT as well as enhancement patterns and time-attenuation curves by contrast-enhanced dynamic CT.

A case of solitary pulmonary lymphangioma.

Solitary pulmonary lymphangiomas are rare benign lesions thought to result from the development of abnormally proliferating lymphatic vessels. This report describes a case of solitary pulmonary lymphangioma resected under video assisted thoracoscopic surgery and diagnosed using histological and immunohistochemical investigations.

Pulmonary lesions associated with Sjögren's syndrome: radiographic and CT findings.

The aim of this study was to analyse and compare the chest radiographic and CT findings in patients with primary and secondary Sjögren's syndrome. We retrospectively evaluated the frequency of abnormality and findings of both the chest radiography (n=107) and CT (n=59) in patients with Sjögren's syndrome. Abnormal cases were classified into five patterns based on predominant CT findings. Chest radiographic and CT abnormalities were seen in 24 (22%) and in 34 (58%) patients, respectively. Most frequently observed abnormal findings were linear and reticular opacities on chest radiograph, and ground-glass opacity, interlobular septal thickening and intralobular interstitial thickening on CT in both primary and secondary Sjögren's syndrome. Centrilobular abnormalities were significantly more common in patients with primary Sjögren's syndrome (p=0.018). According to our CT classification, interstitial pneumonia (IP) pattern was the most common in patients with both primary and secondary Sjögren's syndrome. Bronchiolitis pattern was more common in patients with primary Sjögren's syndrome and lymphoproliferative disorder (LPD) pattern was only observed in primary Sjögren's syndrome. In conclusion, although the most frequently observed pattern in our CT classification was IP pattern in both primary and secondary Sjögren's syndrome, centrilobular abnormalities and LPD pattern were relatively characteristic in patients with primary Sjögren's syndrome.

Anterior mediastinal bronchogenic cyst: demonstration of complicating malignancy by CT and MRI.

A case is presented of anterior mediastinal bronchogenic cyst associated with adenocarcinoma arising from the cyst wall. The presence of a solid component in the lower portion of the mass was suspected from CT and confirmed by MRI.

Radiographic and CT appearances of the major fissures.

The major fissure is an important anatomic landmark in the interpretation of chest radiographs and computed tomographic (CT) scans. At radiography, the major fissures normally appear as hairlines of soft-tissue density; at conventional CT, they typically appear as lucent, hypovascular bands; and at high-resolution CT, they most often appear as sharp lines. The superolateral major fissure usually manifests as a curving edge at the upper lateral lung field with lateral opacity and medial lucency. The vertical fissure line appears as a fine, linear shadow, commencing in or near the costophrenic angle and coursing upward. The superomedial major fissure manifests as a short, obliquely oriented straight line. Progressive widening of the major fissure inferiorly manifests as a triangular area of increased opacity and represents intrafissural fat. Various inflammatory, granulomatous, neoplastic, and abnormal hemodynamic conditions involving the major fissure can affect its imaging appearance. Oblique orientation of the major fissure may complicate radiographic interpretation. The fissure may be incomplete or absent, complicating identification of various diseases. An incomplete major fissure may lead to disease spread, collateral air drift, or the "incomplete fissure sign," a sign that may, however, also be present in cases of complete fissure. Knowledge of the anatomy and normal variants of the major fissures is essential for recognizing their variable imaging appearances as well as related abnormalities.

Fas/FasL mediated apoptosis of thyrocytes in Graves' disease.

We examined in the present study the possible involvement of Fas and its ligand (FasL) in the process of Graves' disease. Immunohistochemical analysis showed that few normal thyrocytes expressed Fas but many thyrocytes in Graves' disease expressed this molecule. The percentage of FasL-positive thyrocytes in Graves' thyroids was, however, less than in normal thyroids. Several apoptotic thyrocytes and infiltrating mononuclear cells (MNCs) were detected scattered throughout Graves' thyroid tissues and abundant proliferating cell nuclear antigen (PCNA)-positive thyrocytes were present. Apoptotic cells, as well as PCNA-positive cells, were scarcely detectable in normal thyroid glands, however. In vitro treatment of thyrocytes by IL-1beta a cytokine found to be expressed in Graves' thyroid glands, increased Fas but reduced FasL expression. IL-1beta-stimulated thyrocytes became sensitive to apoptosis by anti-Fas IgM monoclonal antibody (mAb). Activated T cells, which strongly expressed FasL, showed cytotoxic activity toward IL-1beta-stimulated thyrocytes but not toward unstimulated thyrocytes. This cytotoxic activity involved the Fas/FasL pathway. Importantly, unstimulated thyrocytes could kill activated, but not resting, T cells. IL-1beta-stimulated thyrocytes, with down-regulated FasL expression, could not efficiently kill activated T cells. The cytotoxic activity of unstimulated thyrocytes toward activated T cells was inhibited by anti-FasL mAb. Interestingly, unstimulated thyrocytes induced apoptosis in IL-1beta-stimulated thyrocytes but not in unstimulated thyrocytes. These interactions were also blocked by anti-FasL mAb. Our results suggest that the apoptotic cell death of both thyrocytes and infiltrating MNCs found in Graves' thyroid glands is regulated by IL-1beta through Fas/FasL interactions.

[A case of primary racemose hemangioma of bronchial artery with recurrent hemoptysis].

A 42-year old man was admitted to our hospital because of hemoptysis. Bronchial arteriography revealed a tortuous and dilated left bronchial artery with a shunt formation between the bronchial and pulmonary arteries. Bronchial artery embolization using a sponge was performed three times to treat the hemoptysis, but all attempts failed. The patient therefore underwent left lower lobectomy, after which no hemoptysis was observed. Histopathologically, the resected tissue showed no inflammatory change. Interestingly, abnormal vessels resembling arteriovenous malformations were also found. Although the embolization therapy was effective in several reported cases, we concluded that surgery was required for this patient with persistent hemoptysis because of the development of collaterals and a bronchial-pulmonary artery shunt.

[CT-guided needle biopsy of the lung: factors affecting risk of complications].

PURPOSE: To analyze factors influencing the risk of complications associated with CT-guided percutaneous needle biopsy for lung lesions. MATERIALS AND METHODS: Sixty patients, aged 24-85 years (37 men and 23 women), underwent CT-guided needle biopsy. A definite diagnosis was made in 49 of 60 cases (81.7%), including 38 of 43 malignant lesions (88.4%) and 11 of 17 benign lesions (64.7%). Complications associated with biopsy were observed in 35 patients (58.3%). Major complications included pneumothorax (n = 26) and pulmonary hemorrhage (n = 20). Chest tube placement was needed in 5 (19.2%) of 26 pneumothorax cases (8.3% of all biopsies). RESULTS: The high frequency of pneumothorax (43.3%) in this series had several contributing factors, including the presence of pulmonary emphysema, lesion size, and traversal of aerated lung. Chest tube replacement was necessary more frequently in patients with pulmonary emphysema. The number of pleural passes, location of lesions, and size of needles were not correlated with the incidence of pneumothorax. CONCLUSION: The presence of pulmonary emphysema, lesion size, and traversal of aerated lung are the predominant risk factors for pneumothorax in patients with CT-guided lung biopsy.

Lobar atelectasis: diagnostic pitfalls on chest radiography.

This pictorial review looks at the pitfalls in the diagnosis of lobar atelectasis on chest radiographs. Lobar atelectasis with marked volume loss is hard to recognize and may be easily missed. Lobar atelectasis presenting as a mass-like opacity may be misdiagnosed as mediastinal or lung tumour. Lobar atelectasis in an unusual location may also be misdiagnosed as other entities. Familiarity with such manifestations and consideration of anatomical alterations as the signs of lobar atelectasis are important in making the correct diagnosis.

Elevation of serum pro-gastrin-releasing peptide in patients with medullary thyroid carcinoma and small cell lung carcinoma.

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid gland and produces a variety of peptides such as calcitonin (CT) and gastrin-releasing peptide (GRP). Here we measured serum levels of pro-gastrin-releasing peptide (Pro-GRP), a more stable precursor of GRP, in 15 patients with MTC (4 males, 11 females) who did not show any clinical or radiologic signs of small cell lung cancer. Serum Pro-GRP levels were elevated in 80% (12/15) patients. Significant correlation was observed between serum Pro-GRP and CT (r = 0.52) and carcinoembryonic antigen (CEA) (r = 0.56). Serum Pro-GRP levels also correlated with tumor size (r = 0.70). Serum Pro-GRP levels also decreased below the cut-off range in one patient after surgical resection. Our data suggest that Pro-GRP, which is considered to be a specific marker for small cell lung carcinoma, seems to be also helpful and additional marker for the diagnosis and monitoring the response to therapy in patients with MTC in addition to calcitonin as the main tumor marker.

Anaplastic changes associated with p53 gene mutation in differentiated thyroid carcinoma after insufficient radioactive iodine (131I) therapy.

Thirty-two patients with differentiated thyroid carcinomas with distant metastasis were examined using a radioactive iodine (131I) tracer dose prior to 131I therapy and followed up for 10 years or until death (whichever occurred first). Nineteen patients who received 131I therapy had an accumulation of 131I in the metastases (group I) and 15 of those patients were alive more than 10 years after the first 131I treatment. In contrast, all 13 patients in whom the metastases did not show accumulation of 131I died within 10 years. Of the latter group, eight patients had received 131I therapy (group II), four of whom died with anaplastic changes within 5 years of treatment. p53 gene mutation was identified by immunohistochemistry in primary thyroid carcinoma tissue from patients with anaplastic changes that were evident during total thyroidectomy. Five patients did not receive 131I therapy (group III), of whom one, who also had a p53 gene mutation in the original tumor, died with anaplastic change 10 years after thyroidectomy. Seven patients in group I had p53 gene mutations in their thyroid carcinoma tissues, but none showed anaplastic changes. Our results suggest that 131I therapy may be useful for patients with distant metastases, with or without p53 gene mutations, which show accumulation of 131I from tracer and therapeutic doses. In contrast, 131I therapy is apparently not effective in patients who do not show sufficient accumulation of 131I, but rather, may cause early anaplastic changes with a p53 gene mutation.

Etidronate inhibits human osteoblast apoptosis by inhibition of pro-apoptotic factor(s) produced by activated T cells.

Humoral factors produced by activated T cells are thought to be important in the development of bone loss in patients with rheumatoid arthritis (RA). We investigated the inhibitory effect of etidronate disodium (EHDP) on apoptosis of human osteoblasts induced by supernatants from in vitro activated T cell cultures. Human osteoblastic cell line MG63 cells and human primary osteoblast-like cells were used in the present study as human osteoblasts. T cells were incubated with interleukin-2 and further activated with 1 2-o-tetradecanoyl-phorbol 13-acetate and ionomycin, either in the presence or absence of EHDP. After we carried out the cultivation, we examined the cytotoxicity of cultured T cell supernatants toward MG63 cells and human primary osteoblast-like cells. Supernatants from activated but not resting T cell cultures efficiently induced apoptosis of MG63 cells and primary osteoblast-like cells. Supernatants from activated T cell cultures, incubated with EHDP, exhibited significantly less cytotoxicity than did supernatants incubated in the absence of EHDP. In contrast, the cytotoxicity of activated T cell culture supernatants was not affected by direct treatment of human osteoblasts with EHDP. The concentration of soluble Fas ligand in activated T cell culture supernatants was actually increased by EHDP. However, EHDP did not influence soluble Fas and tumor necrosis factor-alpha concentrations in the supernatant. Furthermore, treatment of human osteoblasts with EHDP did not alter their expression of Bcl-2/Bcl-xL or their sensitivity to anti-Fas immunoglobulin M-induced apoptosis. Our results suggest that EHDP inhibits the production of soluble factor that induces apoptosis of human osteoblasts and thus exhibits a protective action toward human osteoblast apoptosis induced by activated T cell culture supernatants. Although the exact EHDP-regulated molecule that induces apoptosis of human osteoblasts is unknown at present, our study may explain part of the therapeutic action of bisphosphonates in RA complicated by bone loss.

In vitro effects of beta-carotene for the motility, ATP, and intracellular free Ca(2+) concentrations of fowl spermatozoa.

The motility of intact fowl spermatozoa was vigorous at 25 degrees C, but decreased gradually following the addition of 0-100 microM beta-carotene in a dose-dependent manner. Even in the presence of stimulators of fowl sperm motility, such as Ca(2+) or calyculin A, the motility of intact spermatozoa at both 25 and 40 degrees C remained inhibited following the addition of beta-carotene. Under all of these circumstances, sperm ATP concentrations were not reduced by the addition of beta-carotene. Moreover, the motility of demembranated spermatozoa was not inhibited by the addition of the same concentrations of beta-carotene. No changes in intracellular free Ca(2+) concentrations, measured by means of a fluorescent Ca(2+) indicator, fura-2, were observed in intact beta-carotene -treated spermatozoa. These results suggest that beta-carotene is involved in the inhibition of the flagellar movement of fowl spermatozoa without change in energy production, and that the target of beta-carotene might be present in the cytoplasmic matrix and/or the plasma membrane, but not retained in the axoneme and/or accessory cytoskeletal components.

The possible role of protein-carboxyl methylation in the regulation of flagellar movement of fowl spermatozoa.

Both intact and demembranated fowl spermatozoa were incubated at 30 degrees C and 40 degrees C with adenosine, 3-deazaadenosine and homocysteine thiolactone. This combination of products is known to block intracellular protein-carboxyl methylation reaction. The motility of intact spermatozoa incubated at 30 degrees C was vigorous but decreased markedly after the addition of 100 microM adenosine+100 microM 3-deazaadenosine+100 microM homocysteine thiolactone. During this incubation period, the intracellular ATP concentrations of spermatozoa were maintained at approximately 40 nmol ATP/10(9) cells, in spite of the inhibition of motility. The motility of demembranated spermatozoa at 30 degrees C was not inhibited by the same concentrations of blocker. At 40 degrees C, the motility of intact spermatozoa without any effectors was almost negligible. The addition of blocker did not appreciably affect the motility of spermatozoa, which remained almost negligible. In contrast, motility became vigorous even at 40 degrees C when intact spermatozoa were suspended in fluid to which had been added 1 mM CaCl(2) or 100 nM calyculin A, a specific inhibitor of protein phosphatase-type 1 and -type 2. Stimulation of motility by Ca(2+) or calyculin A was inhibited by the presence of a blocker. Contrary to that of intact spermatozoa, the motility of demembranated spermatozoa stimulated by protein phosphatase inhibitor at 40 degrees C was not inhibited by the presence of a blocker. These results suggest that protein-carboxyl methylation may be involved in the regulation of fowl sperm motility. Furthermore, it appears that the methylating enzyme may be present in the cytoplasmic matrix and/or the plasma membrane but not retained in the axoneme and/or accessory cytoskeletal components.

Computerized analysis of the likelihood of malignancy in solitary pulmonary nodules with use of artificial neural networks.

PURPOSE: To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) to assist radiologists in the distinction of benign and malignant pulmonary nodules. MATERIALS AND METHODS: Fifty-six chest radiographs of 34 primary lung cancers and 22 benign nodules were digitized with a 0.175-mm pixel size and a 10-bit gray scale. Eight subjective image features were evaluated and recorded by radiologists in each case. A computerized method was developed to extract objective features that could be correlated with the subjective features. An ANN was used to distinguish benign from malignant nodules on the basis of subjective or objective features. The performance of the ANN was compared with that of the radiologists by means of receiver operating characteristic (ROC) analysis. RESULTS: Performance of the ANN was considerably greater with objective features (area under the ROC curve, Az = 0.854) than with subjective features (Az = 0.761). Performance of the ANN was also greater than that of the radiologists (Az = 0.752). CONCLUSION: The computerized scheme has the potential to improve the diagnostic accuracy of radiologists in the distinction of benign and malignant solitary pulmonary nodules.