Lung adenocarcinoma with bronchioloalveolar carcinoma component is frequently associated with foci of high-grade atypical adenomatous hyperplasia

We assessed the occurrence of atypical adenomatous hyperplasia (AAH) in whole lung lobes with primary cancer lesions. Following surgical resection, tissue specimens were sliced to a thickness of 4 mm (3,641 specimens from 61 cases; mean = 59.7 specimens per case). A total of 119 AAH foci were found and an association was evident in 25 (57%) of 44 adenocarcinomas, 3 (30%) of 10 squamous cell carcinomas, and 2 (29%) of 7 other lung cancers. Histologic evaluation showed that 108 AAH foci were categorized as low-grade and the other 11 as high-grade AAH. These 11 foci of high-grade AAH were present in 7 patients with adenocarcinoma, and in 1 patient there was a synchronous double primary lung adenocarcinoma. High-grade AAH was closely associated with bronchioloalveolar carcinoma (BAC) type adenocarcinoma, and low-grade AAH with non-BAC adenocarcinoma. The mean +/- SD Ki-67 labeling index in high-grade AAH (3.5%+/-2.9%) was significantly higher than for the low-grade index (1.4%+/-1.6%). We propose that foci of high- but not low-grade AAH may be potential precursor lesions of lung adenocarcinoma, especially with the BAC component.     

Role of apoptosis controlled by cytochrome c released from mitochondria for luteal function in human granulosa cells

PROBLEM: The aim of this study was to investigate the relationship between apoptosis by the mitochondrial pathway and luteal function in human granulosa cells. METHOD OF STUDY: Granulosa cells were obtained by ultrasound-guided follicular aspiration from patients undergoing in vitro fertilization and embryo transfer. After the addition of RU486, cells were stained with a mitochondria-specific fluorescent dye, MitoTracker Red CM x Ros. Using flow cytometry and National Institute of Health image, the mitochondrial fluorescent area was measured. After staining with Hoechst 33258 dye, the number of apoptotic bodies per 1000 cells were counted at random on photomicrographs. Homogenates were used for sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blot analysis using antibodies against cytochrome c or caspase-3. RESULTS: The incidence of apoptotic bodies increased and the mitochondrial membrane potential decreased time dependently. The opposite effect was observed dose dependently with RU486 treatment. Western blot analysis showed increased cytochrome c expression, after treatment with 1-2 microg/mL of RU486 which then decreased with 5-10 microg/mL of RU486. Caspase-3 expression increased dose dependently with RU486. CONCLUSIONS: These results suggest that the activation of caspase-3 caused by cytochrome c released from mitochondria plays an important role in apoptosis-related luteal function in human granulosa cells.     

Effects of dual-action genistein derivatives on relaxation in rat aorta.

Protein tyrosine kinases and nitric oxide (NO) play important roles in several cardiovascular diseases. In this study, we examined the actions of two compounds, each has structure of genistein (a tyrosine kinase inhibitor) and an NO donor, on endothelium-independent relaxation responses in the isolated rat aorta. By rational drug design, genistein was modified to acquire an NO donor, and we synthesized two such compounds (G-II, G-VI). These compounds and genistein induced dose-dependent relaxation responses in endothelium-denuded aortic strips, the rank order of potencies being G-VI > G-II > genistein. Incubation of endothelium-denuded strips with 1H-[1,2,4] oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ, 10 microM), a guanylyl cyclase inhibitor, inhibited both the G-II- and G-VI-induced relaxations, but not the genistein-induced relaxation. The residual relaxations induced by these two compounds were similar to the genistein-induced relaxation. Incubation of endothelium-denuded strips with lysophosphatidylcholine (LPC, 20 microM)-which is a major atherogenic lysophospholipid component of oxidized low-density lipoprotein and is known to activate tyrosine kinase-caused a significant rightward shift in the dose-response curve for genistein. LPC also shifted the G-II- and G-VI-induced relaxation curves to the right; however, these relaxations in the presence of LPC were greater than that induced by genistein. The sodium nitroprusside-induced relaxation in endothelium-denuded strips was similar between in the absence and presence of LPC. These results suggest that each of our newly developed G-II and G-VI compounds has a dual action, as an NO donor and a tyrosine kinase inhibitor. These compounds may be useful against certain cardiovascular diseases.     

Long-term inhibition of intimal hyperplasia using vascular photodynamic therapy in balloon-injured carotid arteries

Flexible treatments for intimal hyperplasia after angioplasty are still needed. The aim of this study was to demonstrate the long-term effects of vascular photodynamic therapy with talaporfin sodium on intimal hyperplasia following interventional injury. Intimal hyperplasia was induced by balloon distension injury to the carotid artery in 31 rabbits. Talaporfin, 5.0 mg/kg, was delivered systemically immediately after balloon injury. The injury site was irradiated with a diode laser light of wavelength 664 nm using a fluence of 50 J/cm² after 30 min. At day 3 and weeks 3, 6, 9, 15, and 25 after photodynamic therapy, the treated artery of each rabbit was excised and examined immunohistochemically. Thirty minutes after talaporfin administration, drug fluorescence was found only in the balloon-injured carotid artery wall. At 3 days, no smooth muscle cells were seen in the media of the photodynamic therapy-treated arterial segments. Intimal hyperplasia developed progressively in the balloon-injured and untreated segments; however, in the segments treated with photodynamic therapy, intimal hyperplasia was markedly suppressed until 25 weeks and the media was repopulated by smooth muscle cells without macrophages. Vascular photodynamic therapy with talaporfin may be used to inhibit restenosis after vascular intervention. An erratum to this article is available at .     

Expression of matrix Gla protein and osteonectin mRNA by human aortic smooth muscle cells.

BACKGROUND: Recent data indicate that matrix proteins such as matrix Gla protein (MGP) and osteonectin (ON) influence not only mineralization of vasculature but smooth muscle cell (SMC) differentiation. METHODS: We examined whether MGP and ON are expressed by human aortic SMCs in vivo using Northern blotting, in situ hybridization and immunohistochemistry. RESULTS: MGP and ON mRNAs were strongly expressed in the aorta without atherosclerosis from newborn and four young subjects up to 10 years old. In the aorta from 15 adult cases, MGP and ON mRNAs were decreased as atherosclerosis developed. We determined cell type and distribution of the MGP- and ON mRNA-expressing cells by in situ hybridization and immunohistochemistry. In the aorta obtained from newborn and young subjects, SMCs in the media and thin intima expressed MGP mRNA and, to a lesser extent, ON mRNA. In the adult aorta with fibrous thickening, MGP mRNA was expressed by intimal SMCs and subpopulation of medial SMCs. Osteonectin mRNA was expressed mainly by intimal SMCs and few medial SMCs. Double immunohistochemical staining revealed that both MGP- and ON protein-expressing cells were positive for anti-alpha-smooth muscle actin antibody, aortic SMCs. CONCLUSIONS: These results suggested that MGP and ON expression by aortic SMCs might be regulated by the degree of atherosclerosis and SMC differentiation in human aorta.     

Does action semantic knowledge influence mental simulation in sentence comprehension?

This research investigated whether action semantic knowledge influences mental simulation during sentence comprehension. In Experiment 1, we confirmed that the words of face-related objects include the perceptual knowledge about the actions that bring the object to the face. In Experiment 2, we used an acceptability judgment task and a word-picture verification task to compare the perceptual information that is activated by the comprehension of sentences describing an action using face-related objects near the face (near-sentence) or far from the face (far-sentence). Results showed that participants took a longer time to judge the acceptability of the far-sentence than the near-sentence. Verification times were significantly faster when the actions in the pictures matched the action described in the sentences than when they were mismatched. These findings suggest that action semantic knowledge influences sentence processing, and that perceptual information corresponding to the content of the sentence is activated regardless of the action semantic knowledge at the end of the sentence processing.     

Total hip arthroplasty using a Kerboull-type plate for rapidly destructive coxarthrosis: comparison with uncemented acetabular component

Introduction

Clinical outcomes of total hip arthroplasty (THA) to treat rapidly destructive coxarthrosis (RDC) have been reported, but to our knowledge, there have been no studies comparing implants. The aim of this study was to examine the effectiveness of acetabular reconstruction for RDC by comparing the clinical results of THA using a Kerboull-type plate with an uncemented cup.

Patients and methods

Among 921 primary THAs performed between 2006 and 2014, 27 were performed for the treatment for RDC using a Kerboull-type plate or a conventional uncemented cup. A Kerboull-type plate for acetabular reinforcement device was used in 13 hips and an uncemented cup in 14 hips. The mean follow-up period was 61.2 months.

Results

The duration of surgery was 156.8 ± 36.4 min in the Kerboull-type plate group and 103.3 ± 14.4 min in the uncemented cup group, being significantly longer in the former (P = 0.0002). In the Kerboull-type plate group and the uncemented cup group, the 5-year survival rates were 100 and 83.9 %, respectively. Recurrent dislocation was observed in two cases in which the posterior approach had been used.

Conclusions

In our study, the loosening of the acetabular components was noted in 14.3 % of uncemented cup-applied cases, but no loosening was noted in any Kerboull-type plate-applied case. Therefore, for RDC, in which objective evaluation of fragile bone quality is difficult, the use of the Kerboull-type plate, which disperses weight-bearing of the acetabular, may be an effective means to achieve early functional recovery as well as a long-term favorable outcome.

     

Bilateral subclavian steal associated with severe coarctation of the thoracic aorta and an aberrant right subclavian artery

A 10-year-old girl having bilateral subclavian steal associated with severe coarctation of the thoracic aorta and an aberrant right subclavian artery was found, on admission, to have no difference between upper and lower extremity blood pressure, but echocardiography revealed severe thoracic aorta coarctation and systolic blood pressure in the carotid arteries exceeding 200 mmHg estimated by Doppler ultrasonography. Magnetic resonance imaging and angiography demonstrated bilateral subclavian steal without esophageal compression. We reconstructed the aortic arch using the left subclavian artery and a reversed Blalock-Park procedure, then repaired the coarctation with a 14 mm woven double velor vascular graft. The girl was symptom-free following uncomplicated recovery from surgery. Doppler ultrasonography 2 weeks after surgery showed the pressure gradient across the aortic arch had decreased from 180 mmHg to 60 mmHg. This residual gradient at the anastomosis between the ascending aorta and left subclavian artery may improve as native vessels grow.     

Changes in the activity of the cerebral cortex relate to postural response modification when warned of a perturbation.

OBJECTIVE: To determine whether the cerebral cortex contributes to modifying upcoming postural responses to external perturbations when provided with prior warning of the perturbation. METHODS: Electroencephalographic (EEG) potentials were recorded from 12 healthy human subjects (21-32 years of age) before perturbing their balance with backward translations of a platform under their feet. The subjects responded with and without a visual cue that warned them 2s before the perturbation (the Cue and No Cue conditions, respectively). RESULTS: Contingent negative variation (CNV) was evident before perturbation onset in only the Cue condition. In the Cue condition, the subjects also produced smaller center of pressure (CoP) displacements than in the No Cue condition. The cue-related difference in the subjects' CNV potentials correlated with the cue-related difference in their CoP displacements. No significant associations existed among the CNV potentials and any cue-related postural adjustments made before the perturbation. CONCLUSIONS: Cortical activity before an externally triggered perturbation associates with modifications of the ensuing postural response. SIGNIFICANCE: This is the first study to demonstrate a cortical correlate for changes in central postural set that modify externally triggered postural responses based on anticipation.     

A case of successful resection of pulmonary arteriovenous fistula with a high shunt ratio

We report on a 25-year-old cyanotic man who was diagnosed as having a pulmonary arteriovenous fistula. His chief complaint had been shortness of breath since childhood. Polycythemia (Hb 21.4 g/dl) was detected during a health checkup at his company. A chest X-ray showed an abnormal mass in the left lung. Blood gas analysis showed severe hypoxia with PaO₂ of 38.6 mmHg at room air. Angio-CT showed a large aneurysmal lesion at S6 of the left lung with a large feeding artery and vein. Oxygen saturation was 75.2% in the radial artery and 62.5% in the right atrium. The right-to-left shunt ratio was therefore calculated as 62%. The aneurysmal lesion was resected by segmentectomy of the left S6 following division of A6 and V6. After a successful operation, the patient no longer had shortness of breath or cyanosis and blood gas analysis showed PaO₂ as 84.3 mmHg at room air. Pulmonary angiography showed no residual shunt lesion.