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Biomedical subjects

Kazuo Motoyoshi

Publications and source records attributed to Kazuo Motoyoshi.

At least 19 recordsLinked to original sources

M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: the critical role of the SDF-1-CXCR4 system.

OBJECTIVE: Since the macrophage colony-stimulating factor (M-CSF) has been shown to stimulate differentiation and proliferation of monocyte/macrophage lineage and to be involved in the process of neointimal formation after vascular injury, we tested the effects of M-CSF on the recruitment of bone marrow-derived progenitor cells in neointimal formation after vascular injury in mice. METHODS AND RESULTS: Wire-mediated vascular injury was produced in the femoral artery of C57BL/6 mice. Recombinant human M-CSF [500 microg/(kg x day)] or saline (control) was administered for 10 consecutive days, starting 4 days before the injury. Treatment with M-CSF accelerated neointimal formation in the early phase after injury, and this neointimal lesion mainly consisted of bone marrow-derived cells. M-CSF treatment had no effect on the mobilization of endothelial progenitor cells (EPCs: CD34+/Flk-1+) and reendothelialization after injury. The stromal cell-derived factor-1 (SDF-1) was markedly expressed in the neointima and media after injury, whereas CXCR4+ cells were observed in the neointima. Further, a novel CXCR4 antagonist, AMD3100, significantly attenuated the M-CSF-induced neointimal formation. CONCLUSIONS: These findings suggest that M-CSF accelerated neointimal formation after vascular injury via the SDF-1-CXCR4 system, and the inhibition of this system has therapeutic potential for the treatment of cardiovascular diseases.

Animals↗

Squamous Cell Carcinoma of the Lung Spreading Along the Alveolar Walls With a Bubblelike Appearance on HRCT.

On health examination, a nodular opacity of size of 25 mm was detected in a 54-year-old man. High-resolution computed tomography scans showed irregular-shaped ground glass opacity with bubble-like appearance in the right lung. The low-magnified histological findings after right upper lobectomy demonstrated squamous cell carcinoma that progressed along the alveolar septum and resembled the growing pattern of bronchioloalveolar carcinoma. As the mechanism of the formation of air density on computed tomography, the presence of check valve phenomenon was estimated. Squamous cell carcinoma of the lung that multiplies along alveolar walls shows localized ground glass opacity including air density areas similar to those in bronchioloalveolar carcinoma on high-resolution computed tomography.

Carcinoma, Squamous Cell↗

Clarithromycin delays progression of bronchial epithelial cells from G1 phase to S phase and delays cell growth via extracellular signal-regulated protein kinase suppression.

The nonsteroidal anti-inflammatory drugs have been shown to support cytoprotection of cells by shifting cells toward a quiescent state (G(0)/G(1)). Extracellular signal-regulated kinase (ERK) is required for cells to pass from G(1) phase into S phase, and macrolide antibiotics can inhibit ERK1/2 phosphorylation. However, previous reports suggest that macrolide antibiotics do not affect cell growth in bronchial epithelial cells. Therefore, we studied normal human bronchial epithelial (NHBE) cells to determine whether clarithromycin (CAM) suppresses ERK, delays bronchial epithelial cells from progressing to S phase, and delays cell growth. Exposure to CAM at 10 microg/ml daily over 4 days irreversibly decreased the cell proliferation with and without growth supplements (P < 0.0001). CAM also inhibited ERK1/2 phosphorylation over the first 90 min of exposure (P < 0.05 for 30 min, P < 0.0001 for 60 min, and P < 0.01 for 90 min) and decreased the ratio of phosphorylated ERK1/2 (pERK1/2) to total ERK1/2 (tERK1/2) (P < 0.0001). Incubation with CAM for 48 h increased the proportion of cells in G(1) phase (means +/- standard deviations) from 63.5% +/- 0.9% to 79.1% +/- 1.4% (P < 0.0001), decreased that in S phase from 19.8% +/- 1.2% to 10.0% +/- 2.1% (P < 0.01), and decreased that in G(2)/M phase from 16.7% +/- 0.4% to 11.0% +/- 0.8% (P < 0.001). In contrast, the ratio of pMEK1/2 to tMEK1/2 was not altered after exposure to CAM. These results suggest that macrolide antibiotics can delay the progression of NHBE cells from G(1) phase to S phase and can slow cell growth, probably through the suppression of ERK1/2.

Anti-Bacterial Agents↗

[Disseminated Mycobacterium avium infection in an immunocompetent aged patient].

We reported an immunocompetent elderly patient with disseminated Mycobacterium avium infection exhibiting bronchial, pulmonary, nodal, otitic and osteitic lesions. An 82-year-old man was initially hospitalized with cervical and mediastinal lymphadenopathy. M. avium was demonstrated in gastric juice and a lymph node. An endobronchial polypoid lesion was formed by perforation of mediastinal mycobacterial lymphadenitis into the right main bronchus. Combined treatment by CAM, RFP, EB, and SM caused the lesions to diminish and the treatment was continued for 18 months. One year after completion of treatment the patient was re-admitted with complaints of left ear pain, and a subcutaneous abscess on his back. M. avium was again demonstrated from external ear exudate and aspirated subcutaneous pus. Re-treatment with combined chemotherapy induced prompt resolution of the ear and bone lesions. It is unusual that immunocompetent patients suffer disseminated non-tuberculous mycobacterial infection, but chest physicians should pay attention to M. avium infection because of its worldwide dissemination.

Aged, 80 and over↗

[Radiological findings in initial pulmonary alveolar proteinosis detected in the post-treatment course of nocardiosis].

Chest CT detected a small localized ground glass opacity in the right upper lung in a 52-year-old woman being treated for nocardiosis. A PAS-stain positive material and elevated surfactant level were confirmed in bronchoalveolar lavage fluid, then a diagnosis of pulmonary alveolar proteinosis was established. In early pulmonary alveolar proteinosis with focal opacity, HRCT can demonstrate the substantial findings of alveolar proteinosis such as a crazy-paving appearance or geographic distribution. We should note that alveolar proteinosis in the early stage is easily overlooked and, in addition, nocardiosis might overlap with alveolar proteinosis.

Anemia, Hemolytic, Autoimmune↗

[BALF lymphocyte CD 4/8 ratio in a case of sarcoidosis with radiological resolution].

A 60-year-old man was given a diagnosis of pulmonary and ocular sarcoidosis. His radiological abnormalities and visual disturbance resolved after two years. Ten years later, at age 70, squamous cell carcinoma was detected in the right lower lobe of the lung. Lymphocyte CD4/8 ratio in bronchoalveolar lavage fluid has remained at a high level for the previous 10 years and was 7.41 immediately before the operation. Chest CT and gallium scintigram could not detect abnormalities in mediastinal or hilar nodes. The tumor and right lower lobe were resected with hilar and mediastinal lymph nodes. Histological examination revealed that there were numerous epithelioid cell granulomas in mediastinal and hilar lymph nodes. BALF analysis reflects residual granulomatous inflammation, even if the radiological findings do not show any abnormalities.

Aged↗

Myeloid/NK cell precursor acute leukemia lost both CD13 and CD33 at first diagnosis.

It has been reported that malignancies of natural killer (NK) cell precursors, which are present in both myeloid and lymphoid antigens, are characterized by immature lymphoblastoid morphology with CD7+, CD33+ and CD56+ phenotype. Here, we report a 18-year-old man who was diagnosed with CD33- and CD13- NK cell precursor acute leukemia at first diagnosis. Following a 3-year remission state, he had a relapse as a testicular tumor and CD33+ myeloid/NK cell precursor acute leukemia after allogenic BMT. This case suggests that myeloid antigens are not necessary for diagnosis of myeloid/NK cell precursor acute leukemia.

Adolescent↗

Acute fibrinous and organizing pneumonia: initial presentation as a solitary nodule.

A 55-year-old man complained of cough and dyspnea. His chest radiograph and CT scan revealed a solitary nodule with a diameter of 2 cm, which showed an air bronchogram and had a hazy contour. After 3 weeks, the radiologic findings changed to diffuse infiltration with small centrilobular nodules, alveolar consolidation, and bronchial wall thickening. The alveoli contained numerous fibrin balls and organizing tissue, which are typical pathologic features of acute fibrinous and organizing pneumonia (AFOP), on histologic examination. We report the initial radiologic features of AFOP and suggest that there are some radiologic similarities between this condition and cryptogenic organizing pneumonia.

Acute Disease↗

Harmful effects of anti-GalNAc-GD1a antibodies and TNF-alpha on rat dorsal root ganglia.

The clinical characteristics of five (22%) of 23 patients with Guillain-Barré syndrome (GBS), whose serum contained immunoglobulin G (IgG) antibodies to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a), included pure motor weakness of the axonal type. These patients had a relatively good prognosis, but displayed higher serum tumor necrosis factor-alpha (TNF-alpha) titers than the other GBS patients. We examined the effect of serum from these patients with IgG anti-GalNAc-GD1a antibodies on neurites from cultured rat dorsal root ganglia (DRG) and found it to damage the myelin in well-elongated DRG neurites and monolayer cultures of Schwann cells and neurons. In the regeneration model, serum from these patients delayed neurite extension and inhibited Schwann cell proliferation. Neurons in cultured monolayers showed vacuolation and decreased rapidly in number. Schwann cells were also vacuolated and readily detached from the substratum. The effects of IgG anti-GalNAc-GD1a antibodies purified from one of the patients, rabbit serum after immunization with GalNAc-GD1a, and recombinant TNF-alpha were also examined. IgG anti-GalNAc-GD1a antibodies mainly inhibited the regeneration and preservation of neurons, while TNF-alpha mainly induced morphological changes in well-proliferated Schwann cells and myelin.

Adolescent↗

Potential involvement of subclinical Sjögren's syndrome in various lung diseases.

OBJECTIVES: Sjögren's syndrome (SS) affects the respiratory system, but previous studies have not assessed the role of subclinical SS in lung disease. The aim of this investigation was to explore the potential role of subclinical SS as a factor in the pathogenesis of various diffuse lung diseases. METHODOLOGY: This single-cohort prospective study was performed over a 5-year period in 313 consecutive patients with diffuse lung disease, who had neither primary xerosis nor a diagnosis of SS. They were referred for the Saxon test and underwent additional tests for SS when decreased saliva production was detected. RESULTS: The subjects included 109 patients with sarcoidosis, 77 with various interstitial pneumonias, 49 with bronchiectasis, and 78 with other diseases. The incidence of decreased saliva production was 17.3% (54 out of 313). A total of 40 of the 54 patients completed further examinations, and definite or probable SS was diagnosed in 29 (9.3% of the original 313). Definite SS was diagnosed in six patients with interstitial pneumonia, three with bronchiolitis, three with sarcoidosis, and five with other diseases. CONCLUSIONS: The prevalence of decreased saliva production and SS without obvious symptoms of dryness was high among patients with diffuse lung disease. In these patients, it is important to screen for SS, even if symptoms are not apparent.

Adolescent↗

A case report of congenital isolated absence of the right pulmonary artery: bronchofibrescopic findings and chest radiological tracings over 9 years.

A 27-year-old man was admitted to hospital for investigation of haemoptysis. He was a serving member of the Japan Self-Defense Forces. A CXR showed absence of the right hilum, and the right hemithorax was smaller than the contralateral hemithorax. Pulmonary arteriography demonstrated complete absence of the right pulmonary artery. Right heart catheterisation did not show any concomitant cardiovascular malformations, and the patient was diagnosed as having isolated absence of the right pulmonary artery. Bronchial arteriograms demonstrated enlargement and proliferation of the small branches of the right bronchial artery. Bronchofibrescopic examination showed obvious enlargement of the bronchial mucosal vessels with submucosal eruptions and swelling in the right bronchial tree, but not on the left side. Re-examination of the patient's CXR from the previous 9 years revealed a chronological decrease of right lung volume and an increase of the cardiothoracic ratio. Isolated absence of the right pulmonary artery is generally considered to have a good prognosis, but close observation is necessary to monitor the pulmonary haemodynamics.

Abnormalities, Multiple↗

Exhaled ethane: an in vivo biomarker of lipid peroxidation in interstitial lung diseases.

BACKGROUND: Oxidative stress plays a role in the pathogenesis and progression of interstitial lung disease (ILD). Exhaled ethane is a product of lipid peroxidation that has been proposed as a biomarker of oxidative stress in vivo. OBJECTIVES: To determine whether the exhaled ethane level is elevated in patients with ILD and to compare it with other clinical parameters. METHODS: Breath samples were collected from 34 patients with ILD, including 13 with idiopathic pulmonary fibrosis (IPF), 9 patients with cryptogenic organizing pneumonia, 6 patients with collagen vascular disease-associated interstitial pneumonia, and 6 patients with pulmonary sarcoidosis. Gas samples were obtained at hospital admission and after 3 weeks. After each expired sample was concentrated using a trap-and-purge procedure, the ethane level was analyzed by gas chromatography. RESULTS: Exhaled ethane levels were elevated in ILD patients (n = 34, mean +/- SD, 8.5 +/- 8.0 pmol/dL) compared with healthy volunteers (n = 16, 2.9 +/- 1.0 pmol/dL; p < 0.001). Serial measurements revealed that increase and decrease of ethane levels were largely consistent with the clinical course. Four patients with IPF who had persistently high ethane levels died or deteriorated, whereas those with ethane levels < 5.0 pmol/dL remained stable or improved. Exhaled ethane concentrations were positively correlated with levels of lactate dehydrogenase (Spearman rank correlation coefficient [rs], 0.28, p = 0.026) and C-reactive protein (rs, 0.38, p = 0.025) and were inversely correlated with Pa(O2) (rs, - 0.40, p = 0.0026). Patients showing increased uptake on (67)Ga scintigraphy demonstrated higher ethane levels (n = 19, 7.5 +/- 5.7 pmol/dL) compared with those who did not show increased uptake on scintigraphy (n = 10, 3.0 +/- 2.4 pmol/dL; p < 0.01). CONCLUSIONS: Exhaled ethane is elevated in patients with ILD and is correlated with the clinical outcome, suggesting that it provides useful information about ongoing oxidative stress, and thereby disease activity and severity in ILD.

Adult↗

Paget-Schroetter syndrome and pulmonary thromboembolism: clinical follow-up over 5 years.

A scaffold constructor lost consciousness at work, leading to emergency admission to our hospital. He had noted gradual worsening of exertional dyspnea over the previous 1 month. Chest radiography showed localized oligemia and enlarged hilar vessels. Pulmonary perfusion scintigraphy confirmed the existence of multiple perfusion defects, so a diagnosis of pulmonary thromboembolism was made. Upper and lower limb venography disclosed interruption of the right subclavian vein (so-called Paget-Schroetter syndrome). However, there was no difference in appearance between the right and left upper extremities. Five years after starting anticoagulant therapy, his symptoms have resolved, but serial perfusion scintigraphy and upper extremity venography revealed the persistence of abnormalities. In patients with pulmonary thromboembolism, lifestyle factors (especially heavy manual labor) should be considered and the possibility of subclavian vein thrombosis should be kept in mind.

Adult↗

[Pulmonary nocardiosis complicated with multiple brain abscess].

A 52-year-old woman was taking 10 mg of prednisolone on alternate days for the treatment of autoimmune hemolytic anemia. She was informed of an abnormality on a chest X-ray film about 3 months previously and was admitted to our hospital with sudden onset of chest pain and fever. On the following day, she underwent transthoracic needle biopsy and the lung lesion was diagnosed as pulmonary nocardiosis. She showed improvement of fever and the lung lesion with administration of an antibacterial agent, but suddenly developed vomiting and headache. Brain MRI revealed multiple brain abscesses at more than 20 sites. A subsequent change of the antibacterial agent achieved control of the lung lesion and brain lesions. This case shows that prednisolone can cause nocardiosis as an opportunistic infection even at a low dose and that antibacterial agents act differently on the lung and brain lesions caused by this organism.

Anemia, Hemolytic, Autoimmune↗

A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene.

Female-to-male hemopoietic stem cell transplantation (HSCT) elicits T cell responses against male-specific minor histocompatibility (H-Y) Ags encoded by the Y chromosome. All previously identified H-Y Ags are encoded by conventional open reading frames, but we report in this study the identification of a novel H-Y Ag encoded in the 5'-untranslated region of the TMSB4Y gene. An HLA-A*3303-restricted CD8(+) CTL clone was isolated from a male patient after an HSCT from his HLA-identical sister. Using a panel of cell lines carrying Y chromosome terminal deletions, a narrow region controlling the susceptibility of these target cells to CTL recognition was localized. Minigene transfection and epitope reconstitution assays identified an 11-mer peptide, EVLLRPGLHFR, designated TMSB4Y/A33, whose first amino acid was located 405 bp upstream of the TMSB4Y initiation codon. Analysis of the precursor frequency of CTL specific for recipient minor histocompatibility Ags in post-HSCT peripheral blood T cells revealed that a significant fraction of the total donor CTL response in this patient was directed against the TMSB4Y epitope. Tetramer analysis continued to detect TMSB4Y/A33-specific CD8(+) T cells at least up to 700 days post-HSCT. This finding underscores the in vivo immunological relevance of minor histocompatibility Ags derived from unconventional open reading frame products.

5' Untranslated Regions↗