Biomedical subjects

K Hiroshima

Publications and source records attributed to K Hiroshima.

At least 19 recordsLinked to original sources

PubMed2006

Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosis.

Pycnodysostosis is a rare hereditary disease, characterized by systemic bone sclerosis. The most important orthopedic problem in this condition is the recurrent pathological fracture of long bones. In this paper, the surgical results for fractures of six limbs (three femurs and three tibias) in five cases of pycnodysostosis are reported. Five limbs achieved fracture union and union is developing in one tibia after intramedullary nail (IM) nailing or Ilizarov external fixation (IEF), although fracture line tends to persist for longer periods of time. One femoral fracture was treated by IM nailing, and one femoral and one tibial fracture were treated by IEF leading to final bone union. One femoral and one tibial fracture were initially treated by IEF, and were treated by IM nailing after re-fracture. One tibial fracture was initially treated by IEF leading to a failure of union, and was converted to IM nailing. All cases are able to walk; one case requires a single crutch. Infection was noted in two limbs after IM nailing following IEF. Fixation with IM nail was effective in preventing re-fracture as well as in alignment correction. Although the surgical technique is more difficult, IM nailing in the initial surgery may be a better choice for achieving successful union while reducing the risk of re-fracture or infection.

Adult↗

PubMed2006

Transbronchial fine needle aspiration cytological examination: a useful tool for diagnosing primary lung cancer.

BACKGROUND: Obtaining a definitive preoperative diagnosis plays a critical role in deciding upon the treatment approach for lung carcinoma. However, success in making definitive diagnoses of small primary lung cancers will require new approaches because these cancers are difficult to detect using standard biopsy procedures. METHODS: We evaluated the results of morphologic definitive diagnosis together with various clinical factors in 1003 primary lung cancers resected surgically. Patients underwent transbronchial brushing, fine needle aspiration cytology, forceps biopsy, and/or forceps biopsy-stamp cytology for preoperative diagnoses, in conjunction with the use of Diff-Quik to confirm that hits had been made on the radiographic shadows before terminating the examinations. RESULTS: Sensitivities of the diagnostic procedures for primary lung cancers were as follows: 64.8% for brushing, 56.1% for transbronchial forceps biopsy, 72.0% for transbronchial forceps biopsy-stamp cytology, and 86.4% for transbronchial fine needle aspiration. The four transbronchial biopsy procedures had a combined overall sensitivity of 92.7%. In patients with peripheral lung cancers of 2 cm or less in diameter, transbronchial fine needle aspiration had a sensitivity of 75.9%, which was the highest sensitivity for all transbronchial examinations. In the subset of 296 patients who underwent all four transbronchial biopsy examinations, transbronchial fine needle aspiration had the highest sensitivity of preoperative diagnosis of all the transbronchial examination methods. CONCLUSIONS: The sensitivity of preoperative cytological diagnosis for primary lung cancers, especially transbronchial aspiration cytology, is high. Transbronchial fine needle aspiration cytology is useful for the preoperative diagnosis of primary lung cancer.

Adolescent↗

PubMed2005

Aberrant methylation of SPARC in human lung cancers.

SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca2+-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinicopathological features. We observed loss of SPARC expression in 12 of 20 (60%) lung cancer cell lines. Treatment of expression-negative cell lines with a demethylating agent restored expression in all cases. Methylation frequencies of SPARC gene were 55% in 20 lung cancer cell lines. Primary tumours had methylation at a rate of 69% (119 of 173), while nonmalignant lung tissues (n=60) had very low rates (3%). In lung adenocarcinomas, SPARC methylation correlated with a negative prognosis (P=0.0021; relative risk 4.65, 95% confidence interval 1.75-12.35, multivariate Cox's proportional-hazard model). Immunostaining revealed protein expression in bronchial epithelium (weak intensity) and in juxtatumoral stromal tissues (strong intensity) accompanied by frequent loss in cancer cells that correlated with the presence of methylation (P<0.001). Our findings are of biological interest and potentially of clinical importance in human lung cancers.

Adenocarcinoma↗

PubMed2005

Frequency of loss of heterozygosity at 3 p, 9 p, 13 q, and 17 p is related to proliferative activity in smokers with stage I non-small cell lung cancer.

BACKGROUND: Tumor cells of lung cancer exhibit genetic abnormalities as well as high proliferative activity. The purpose of this study was to evaluate the relationship of genetic abnormalities and smoking status, histological type, and tumor proliferative activity in resected samples of stage I non-small cell lung cancer (NSCLC). METHODS: We evaluated 126 samples of stage I NSCLC from patients who underwent complete resection between 1988 and 1993. Loss of heterozygosity (LOH) was assessed using primers that amplified polymorphic microsatellite markers at D3S1300, D3S643, D3S1317, D9S171, IFNA, D13S153, and TP53. Expression of Ki-67 nuclear antigen was examined using immunohistochemical methods to assess tumor proliferative activity. RESULTS: The Fractional Regional Loss index (FRL) was significantly higher in squamous cell carcinoma samples than in adenocarcinoma samples (p < 0.0001). In smokers, Ki-67 labeling index (LI) in high-FRL cases was significantly higher than in low-FRL cases (p < 0.0001). CONCLUSION: The frequency of LOH at 3 p, 9 p, 13 q, and 17 p was related to proliferative activity in smokers with stage I non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

A comparison of video and autofluorescence bronchoscopy in patients at high risk of lung cancer.

The aim of this study was to compare the diagnostic yield of flexible video bronchoscopy (FVB) and autofluorescence bronchoscopy (i.e. lung imaging fluorescence endoscopy (LIFE)) in 151 patients at a high risk of lung cancer and with moderate dysplasia or worse on sputum cytology mass screening. Findings from FVB and LIFE were classified as either normal, abnormal or suspicious for cancer. Endobronchial biopsies (EBX) were obtained from abnormal or suspicious areas on FVB and/or LIFE, or randomly when FVB and LIFE were normal. Moderate dysplasia and worse were defined as pathologically positive. Overall, 83 out of 343 (24%) EBX were pathologically positive. The sensitivity of FVB was 72% and LIFE 96%. Relative sensitivity of LIFE over FVB was 1.33. Specificities of FVB and LIFE were 53 and 23%, respectively. The numbers of pathologically positive EBX from sites designated normal, abnormal or suspicious were: from FVB, 23 out of 162 (14%), 37 out of 151 (25%) and 23 out of 30 (77%); from LIFE, three out of 69 (4%), 44 out of 212 (21%) and 36 out of 62 (58%). In normal or abnormal areas at FVB, there was a significant increase in the yield of EBX guided by abnormal and suspicious sites noted at LIFE. In conclusion, endobronchial biopsies of suspicious findings from lung imaging fluorescence endoscopy and flexible video bronchoscopy have a good diagnostic yield. Lung imaging fluorescence endoscopy is more useful when flexible video bronchoscopy is either normal or abnormal.

Adult↗

PubMed2005

Ulnar focal cortical indentation: a previously unrecognised form of ulnar dysplasia.

Deformity of the forearm due to growth disturbance of the ulna occurs in a number of conditions such as ulnar deficiency, multiple exostoses, and neurofibromatosis. We report a previously unrecognised form, caused by focal cortical indentation. We have treated five children with this condition, three girls and two boys; the mean age at presentation was 5 years (2 to 8). The deformity was first recognised about the age of two years, and progressed gradually. The radiological findings were the same in all cases. The focal cortical indentation was seen at the distal end of the ulna with anteromedial bowing and dysplasia. The radial head was dislocated posterolaterally. In one patient the histological findings at the site of indentation were of a fold of tissue resembling periosteum, which interfered with enchondral ossification. Treatment by ulnar lengthening using an external fixator and osteotomy which corrected both the ulnar deformity and reduced the dislocated radial head in two cases gave the best results.

Bone Diseases, Developmental↗

PubMed2005

Dynamics of airborne pollen particles from inhalation to allergic reaction in the nose.

BACKGROUND: Pollinosis is common worldwide, and has been frequently studied. However, the intranasal dynamics of pollen grains have not yet been documented. The purpose of this study is to elucidate for the first time the dynamics of Japanese cedar pollen (JCP) in the human nose at consecutive steps from inhalation to allergic reaction together with release of Cry j 1 (a major allergenic component of JCP) in the nose. METHODS: A personal sampler collected airborne pollens at head height outdoor on the street, while intranasal pollens after natural or experimental inhalation were collected by irrigation with 200ml saline. Cry j 1 in the supernatant after in vitro incubation with phosphate buffered saline or lavage was determined by enzyme-linked immunoassay. RESULTS: Head-height pollen was 183.0 +/- 43.1/300L/h, with 99% of the inhaled pollens deposited on the nasal surface. Eighty eight% of the inhaled pollen was transported to the out-side of the nose by ciliary function within 3 hours. During this process, considerable amounts of Cry j 1 were released in the nose reaching its plateau within 30 min. When the number of pollen deposited exceeded more than approximately 65 particles, symptoms may occur, leading presumably up to a 74% reduction of the intra-nasal pollen. CONCLUSION: The majority of inhaled airborne pollens was deposited on the nasal mucosal surface and moved out from the nose by mucociliary transportation. During this process, when allergenic substances are released up to a critical concentration, allergic reactions occur leading to expelling of pollen from the nose followed by subsiding of the symptoms.

Adult↗

PubMed2004

Clinicopathological analysis of clinical N0 peripheral lung cancers with a diameter of 1 cm or less.

BACKGROUND: The appropriateness of limited resection for small-sized lung cancer continues to be debated. It is not yet clear whether tumor size alone is a reliable indicator for limited resection. METHODS: From 1980 to 2002, 27 patients with clinical N0 peripheral lung cancers having diameters of 1 cm or less underwent pulmonary resection. Clinicopathological features of these cases were reviewed retrospectively. RESULTS: Histological analysis showed that there were 23 cases of adenocarcinoma (81.5 %), two large cell carcinomas (7.4 %), and two carcinoid tumors. Twenty-two cases were classified as pathological stage 1, one was stage II, and four were stage III. Four patients (14.8 %) had lymphatic vessel invasion, three (11.1 %) had lymph node metastasis, and two (7.4 %) had intrapulmonary metastasis. The 5-year disease-free survival rate was 76.6 %. CONCLUSIONS: It is impossible to predict the effectiveness of an intentional limited resection for lung cancer using only tumor size.

Adenocarcinoma↗

PubMed2003

High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer.

BACKGROUND: We investigated the use of high magnification bronchovideoscopy combined with narrow band imaging (NBI) for the detailed examination of angiogenic squamous dysplasia (ASD). This was carried out in relation to bronchial vascular patterns with abnormal mucosal fluorescence in heavy smokers at high risk for lung cancer. METHODS: Forty eight patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light and fluorescence bronchoscopic examination was first performed. Observations by high magnification bronchovideoscopy with conventional white light were made primarily at sites of abnormal fluorescence, and then repeated with NBI light to examine microvascular networks in the bronchial mucosa. Spectral features on the RGB (Red/Green/Blue) sequential videoscope system were changed from the conventional RGB broadband filter to the new NBI filter. The wavelength ranges of the new NBI filter were B1: 400-430 nm, B2: 420-470 nm, and G: 560-590 nm. ASD tissues were also examined using a confocal laser scanning microscope equipped with argon-krypton (488 nm) and argon (514 nm) laser sources. RESULTS: The microvessels, vascular networks of various grades, and dotted vessels in ASD tissues were clearly observed in NBI-B1 images. Diameters of the dotted vessels visible on NBI-B1 images agreed with the diameters of ASD capillary blood vessels diagnosed by pathological examination. Capillary blood vessels were also clearly visualised by green fluorescence by confocal laser scanning microscopy. There was a significant association between the frequency of dotted vessels by NBI-B1 imaging and tissues confirmed as ASD pathologically (p=0.002). CONCLUSIONS: High magnification bronchovideoscopy combined with NBI was useful in the detection of capillary blood vessels in ASD lesions at sites of abnormal fluorescence. This may enable the discrimination between ASD and another pre-invasive bronchial lesion.

Adult↗

PubMed2002

Subepithelial vascular patterns in bronchial dysplasias using a high magnification bronchovideoscope.

BACKGROUND: We have developed a method of high magnification bronchovideoscopy that enables improved observation of subepithelial vascular patterns of the bronchial mucosa. A study was undertaken to investigate the value of high magnification bronchovideoscopy in the detailed examination of dysplasia in the bronchial mucosa of patients with abnormal mucosal fluorescence. METHODS: Thirty one patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light examination was first performed under local anaesthesia and fluorescence bronchoscopy was also carried out using a light induced fluorescence endoscopy (LIFE) lung system. A high magnification bronchovideoscope (XBF 200HM2) was then used to examine the microvascular network in the bronchial mucosa at sites of normal and abnormal fluorescence and the images obtained were compared with pathological diagnoses from bronchial biopsy specimens. Vascular area ratios were calculated using image analysing apparatus. RESULTS: Vascular networks with regular patterns were observed at 20 of 22 abnormal fluorescence sites in biopsy specimens from patients with bronchitis. However, vascular networks with increased vessel growth and complex networks of tortuous vessels of various sizes were observed in 15 of 21 abnormal fluorescence sites in dysplasia specimens. There was a significant difference between bronchitis and dysplasia specimens (OR=25, 95% CI 5.5 to 113, p<0.0001). Mean vascular area ratios from 16 normal bronchial epithelium specimens with normal fluorescence, and 22 bronchitis and 21 dysplasia specimens with abnormal fluorescence were 0.054 (95% CI 0.039 to 0.07), 0.095 (95% CI 0.072 to 0.118), and 0.173 (95% CI 0.143 to 0.203), respectively. The results indicate a statistically significant increase in vascular area in the three groups (p<0.0001). CONCLUSION: Areas of increased vessel growth and complex networks of tortuous vessels in the bronchial mucosa detected using a high magnification bronchovideoscope at sites of abnormal fluorescence may enable discrimination between bronchitis and dysplasia.

Aged↗

PubMed2002

Ehlers-Danlos syndrome type IV with few extrathoracic findings: a newly recognized point mutation in the COL3A1 gene.

Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutation within the COL3AI gene, resulting in the disorder of type III procollagen. The diagnosis is confirmed by demonstrating the synthesis of abnormal type III procollagen molecules from cultured dermal fibroblasts or by identifying the mutation in the COL3A1 gene. The authors report a case of EDS IV caused by a novel point mutation in the COL3A1 gene in a 16-yr-old female. Recurrent haemoptysis and cavitary formation of the lung were evidence of pulmonary involvement. However, extrathoracic manifestations of EDS IV were mostly absent. To the best of the authors' knowledge, all previously reported Ehlers-Danlos syndrome IV patients with respiratory disease had the characteristic findings or histories of Ehlers-Danlos syndrome IV. In the present case, connective tissue friability was suspected due to tissue laceration observed in the biopsied lung specimen, and the diagnosis was made beginning from this pivotal finding.

Adolescent↗

PubMed2001

Hypermutable change of human UV(r)-1 cells by p53 overexpression.

The p53 protein has been reported to regulate cellular responses to genetic stress such as far-ultraviolet light (UV), protecting human cells from mutation. Levels of p53 protein in hypermutable RSa cells were found here to increase soon after UV irradiation, while those in UV(r)-1 cells, a hypomutable variant of RSa cells, showed a delayed increase. Three cell lines overexpressing wild-type p53 in UV(r)-1 cells exhibited higher sensitivity to UV mutagenicity than did control U-V-7 cells transfected with vector alone, assessed using the ouabain-resistance phenotypic mutation test and identification of K-ras codon 12 base substitution mutation. On the other hand, U-V-7 cells showed UV-induced elevation of antipain-sensitive protease activity, but p53 transfectants did not. Moreover, antipain treatment to U-V-7 cells was increased susceptibility to UV mutagenicity. Thus, p53 protein overproduction may sensitize human cells, at least those tested, to UV mutagenicity, in association with inhibition of protease activity.

Cell Division↗

PubMed2001

Apoptosis and proliferative activity in mature and immature teratomas of the mediastinum.

BACKGROUND: Mediastinal teratomas are the most frequent mediastinal germ cell tumor. Whereas mature teratomas are benign tumors, immature teratomas are malignant. The purpose of this study was to find characteristics that could be used to distinguish between the growth and prognosis of the two teratoma types. METHODS: Twenty-four mediastinal teratomas (18 mature and 6 immature) were examined for apoptosis by 3'-end labeling of DNA and stained immunohistochemically for proliferating cell nuclear antigen, Bcl-2, Bax, p53 protein, and alpha-fetoprotein (AFP) expression in formalin fixed, paraffin embedded specimens. RESULTS: AFP was expressed in both immature teratomas and mature teratomas. Whereas p53 protein was expressed by most teratomas, p53 gene mutation was observed in only one patient with an immature teratoma in which the same mutation occurred in all tumor tissue components tested. Bax protein expression was relatively diffuse in mature teratomas but was focally expressed in immature teratomas. Bcl-2 protein was expressed focally in both mature and immature teratomas. Although the proliferative index was significantly higher in immature teratomas compared with mature teratomas (P < 0.001), the apoptotic index (AI) was significantly higher in mature teratomas compared with immature teratomas (P < 0.05). All patients except one in this study remain alive and disease free after undergoing tumor resection. CONCLUSIONS: The relatively high AI in mature teratomas may be due to the overexpression of the p53 protein. In contrast, immature teratomas exhibited higher proliferative activity and lower rates of apoptosis, which may explain the more aggressive behavior of these tumors. However, patients with immature mediastinal teratomas have a good prognosis if the tumor is resected completely after chemotherapy.

Adolescent↗

PubMed2001

Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features.

BACKGROUND: In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma, large cell carcinoma with neuroendocrine differentiation, and large cell carcinoma with neuroendocrine morphology as a variant of large cell carcinoma. Patients with large cell carcinoma with neuroendocrine features have poor prognoses, comparable to those for small cell lung carcinoma. Small cell lung carcinoma is sensitive to chemotherapy; however, it is still unclear whether large cell carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy. METHODS: The authors analyzed 73 patients with large cell carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. RESULTS: In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small cell lung carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy. In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with large cell carcinoma with neuroendocrine features in early stage.

Adult↗

PubMed2001

Increased telomerase activity and elevated hTERT mRNA expression during multistage carcinogenesis of squamous cell carcinoma of the lung.

BACKGROUND: Telomerase activation is believed to play a critical role in the immortalization of cells and carcinogenesis. Telomerase activity is undetectable in normal somatic cells (except for those cells undergoing proliferation) but is expressed in the majority of human tumors including lung carcinoma. The expression of hTERT mRNA has been found to be correlated with telomerase activity. In the current study, the authors analyzed telomerase activity and hTERT mRNA expression in preinvasive bronchial lesions using biopsy specimens obtained by fluorescence bronchoscopy. METHODS: The authors studied 150 bronchial biopsy specimens obtained by fluorescence bronchoscopy. The intensity of telomerase activity was determined by the fluorescence-based telomeric repeat amplification protocol method in 74 bronchial biopsy specimens (22 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 23 dysplasia cases, and 14 squamous cell carcinoma cases), and the level of hTERT mRNA was analyzed in another 76 specimens (24 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 20 dysplasia cases, and 17 squamous cell carcinoma cases) by real-time polymerase chain reaction. RESULTS: The mean values (+/- the standard deviation [SD]) of telomerase activity in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 6.2 +/- 7.5, 13.9 +/- 14.8, 18.5 +/- 20.8, and 54.5 +/- 22.3 U/microg protein, respectively. The upper limit of telomerase activity in normal bronchial epithelium or bronchitis was 21 U/microg protein (mean + 2SD). It is interesting to note that, 5 of 15 squamous metaplasia biopsies (33%), 8 of 23 dysplasia biopsies (35%), and all squamous cell carcinoma biopsies (100%) exhibited levels of telomerase activity that were > 21 U/microg protein. The mean levels of hTERT mRNA in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 891 +/- 840, 1936 +/- 1704, 3019 +/- 2607, and 12965 +/- 18008 copies/microg total RNA, respectively. Telomerase activity and hTERT mRNA expression were found to increase in proportion to the severity of histologic change from normal bronchial epithelium or bronchitis to squamous cell carcinoma. CONCLUSIONS: These results suggest that an increase in telomerase activity and hTERT mRNA expression are features of the early stages of the development of squamous cell carcinoma of the lung, with strong telomerase activity and hTERT mRNA expression being prominent during the latter stages.

Adult↗

PubMed2001

Temporal and spatial distribution of Fos protein in the parabrachial nucleus neurons during experimental tooth movement of the rat molar.

The present study was undertaken to reveal spatio-temporal changes in the distribution of Fos-like immunoreactive (-IR) neurons in the parabrachial nucleus (PBN), one of the important relay nuclei for processing autonomic and somatosensory information from the oro-facial regions, following the induction of experimental tooth movement in rat upper molars. The experimental tooth movement was induced by the insertion of elastic rubber between the first and second upper molars. In normal animals, the PBN contained a smaller number of Fos-IR neurons. Following experimental tooth movement, the Fos-IR neurons increased in number significantly on both the ipsilateral and contralateral PBN, reaching a maximum at 4 h (about 10 times that of normal animals), and then decreased gradually. However, a significant number of Fos-IR neurons remained at 24 h post-operation. Remarkable side-by-side differences in the number of Fos-IR neurons were recognized at 1 to 4 h following the experimental tooth movement. Their number returned to normal (basal) levels at 5 days post. All subnuclei of PBN showed similar temporal changes in the number of Fos-IR neurons, this being particularly apparent in lateral PBN. Administrations of morphine (3 and 10 mg/kg, i.p.) drastically reduced the induction of Fos-IR neurons in all subnuclei of both the ipsilateral and contralateral PBN in a dose-dependent manner, and its effect was antagonized by pretreatment with naloxone (2 mg/kg, i.p.). The reduction of Fos-IR neurons by morphine pretreatment suggests that the appearance of Fos-IR neurons in the PBN may be partly due to the noxious stimulation and/or stress arising from tooth movement. The bilateral expression of Fos-IR neurons in the PBN indicates that the experimental tooth movement causes the activation of PBN neurons for the processing of somatosensory as well as autonomic information. The prolonged expression of Fos-IR neurons in all the subnuclei of bilateral PBN reflects clinical features of the transient discomfort and/or abnormal sensations, which many patients often complain about during orthodontic treatment.

Afferent Pathways↗

PubMed2001

Plasma monocyte chemoattractant protein-1 and pulmonary vascular resistance in chronic thromboembolic pulmonary hypertension.

The pathogenesis of severe pulmonary hypertension seems to be related to inflammatory response in diseased sites. Monocyte chemoattractant protein-1 (MCP-1) has been reported to play a role in the development of congestive heart failure. In this immunological response, activation and migration of leukocytes including macrophages to the inflammatory region are important factors. We hypothesized that the severity of pulmonary hypertension may be related to MCP-1, which is thought to be upregulated by blood pressure or shear stress in pulmonary vasculature as well as by immunological and inflammatory reactions in chronic thromboembolic pulmonary hypertension (CTEPH). Circulating levels of MCP-1, interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) were measured by sandwich ELISA in 14 patients with CTEPH. The plasma level of MCP-1 was significantly correlated with pulmonary vascular resistance. In IL-1beta and TNF-alpha, on the other hand, there was no correlation between cytokines and pulmonary hemodynamics. Pathological specimens obtained from the patients with CTEPH undergoing thromboendarterectomy demonstrated immunoreactivity of MCP-1 in endothelium, smooth muscle cells, and macrophages within neointima in the hypertensive large elastic pulmonary artery. We conclude that MCP-1 is upregulated in the remodeling of pulmonary arteries in close association with increased pulmonary vascular resistance in CTEPH.

Adult↗

PubMed2001

Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology.

BACKGROUND: Large cell carcinoma has been classified as four potential types based on its neuroendocrine morphology and evidence of neuroendocrine differentiation discernible by immunohistochemistry or electron microscopy. However, the clinical relation among these four categories has not been clearly defined. In 1999, the World Health Organization (WHO) categorized large cell neuroendocrine carcinoma as a variant of large cell carcinoma. MATERIAL AND METHODS The authors analyzed 119 cases of large cell carcinoma from a total of 2070 primary lung carcinoma cases resected surgically between 1969-1999. Using light microscopy, electron microscopy, and immunohistochemical staining, the authors reclassified these cases into large cell neuroendocrine carcinoma (LCNEC), large cell carcinoma with neuroendocrine differentiation (LCCND), large cell carcinoma with neuroendocrine morphology (LCCNM), and classic large cell carcinoma (CLCC). RESULTS: In multivariate analyses, the authors found that large cell carcinoma with neuroendocrine features, which combined LCNEC, LCCND, and LCCNM, impacted both the overall survival and disease-free survival of patients. The clinical behavior of LCCNM was similar to that of LCNEC. CONCLUSIONS: Large cell carcinomas with neuroendocrine features appear to be more clinically aggressive than CLCCs. The authors' findings suggest that the histologic identification of neuroendocrine features in tumor tissue from patients diagnosed with large cell carcinoma of the lung may have clinical relevance.

Adult↗