Carnosol Is a Potent Lung Protective Agent: Experimental Study on Mice.

INTRODUCTION: Oxidative stress has been implicated in various disease states and ischemia/reperfusion injury is a direct consequence of oxidative stress in lung transplantation. Because the success rate of organ transplantation in which ischemia/reperfusion is inevitable is highly influenced by oxidative stress, development of strategies to control oxidative stress would be beneficial. Here we identified natural compounds to reduce oxidative stresses in isolated mouse lungs. METHODS: We screened compounds associated with antioxidative stress in 200 plant extracts by monitoring the activities of nuclear factor erythroid 2-related factor 2 (NRF2). Compounds found to ameliorate antioxidative stress were enriched and mice were administered the extract orally every day for 1 week. Then, the lungs were isolated and cultured in the culture medium at 37 °C. Lung damage was monitored by lactate dehydrogenase (LDH) released in the culture medium. Arterial (left ventricle) blood gas levels were also monitored after hilar clamping. RESULTS: We found that Callicarpa longissima extract was rich in NRF2 activators. The responsible compounds were carnosic acid and its oxidative product, carnosol. Carnosol induced heme-oxygenase 1 (HO-1) expression, which is downstream of NRF2, more efficiently than carnosic acid. CONCLUSIONS: Lungs from mice treated with C longissima extract were less damaged than those from control mice and accompanied by HO-1 induction. These results suggest that carnosol is a candidate compound to increase the success rate of lung transplantation.

Lung Transplantation for Lymphangioleiomyomatosis in a Single Japanese Institute, With a Focus on Late-onset Complications.

BACKGROUND: Although late-onset complications are important factors related to inadequate outcomes of lung transplantation (LTx), little is known about them. The results of LTx for lymphangioleiomyomatosis (LAM) patients, which is a large cohort of LTx recipients in Japan, especially with late-onset complications, are reported. METHODS: Thirteen consecutive LTx cases with LAM at our institute were evaluated, and those with late-onset complications were identified. RESULTS: The 5-year survival rate was 69.2%. There were 4 cases with late-onset complications. Case 1: A 35-year-old woman who underwent right single LTx and sustained uncontrollable massive chylous ascites. She underwent placement of a peritoneal-venous shunt, and the ascites was controlled. Unfortunately, she died of small cell cervical cancer (SCCC) 43 months after the LTx. Case 2: A 50-year-old woman who underwent left single LTx had pneumothorax of the native lung 16 months after the LTx. She underwent operative repair of the right lung with a polyglycolic acid (PGA) sheet. She had no recurrence of pneumothorax 1 year after the operation. Case 3: A 33-year-old woman, who underwent left single LTx, had recurrence of LAM in the transplanted lung 2 years after the LTx. She was started on sirolimus. Case 4: A 47-year-old woman, who underwent right single LTx, developed repeated high fevers. She developed an acute abdomen, and swollen subcutaneous lymph nodes were found. After lymph node biopsy, she was diagnosed as having post-transplant lymphoproliferative disorder, and she died 8 months after the LTx. CONCLUSION: It is hoped that these reports and the knowledge gained from them help improve the outcomes of LTx recipients.

Results of surveillance bronchoscopy after cadaveric lung transplantation: a Japanese single-institution study.

BACKGROUND: The prevention and early detection of post-transplantation rejection and infection are key clinical points to achieve long-term survival after lung transplantation. Although surveillance bronchoscopy (SB) is performed in many transplantation centers, it is still controversial because of its undefined clinical significance and its possible complications. We evaluated the clinical utility of SB after cadaveric lung transplantation in Japan, where bilateral transplantation is officially limited to patients medically requiring bilateral grafts. PATIENTS AND METHODS: Twenty-eight patients who underwent cadaveric lung transplantation followed by SB were retrospectively analyzed with reference to the results of bronchoscopy. SB is routinely performed at 1, 2, 3, 6, and 12 months after lung transplantation and annually thereafter. Clinically indicated bronchoscopy (CIB) is considered in patients with suspected rejection or airway infection, and for follow-up examination after treatment for acute rejection. RESULTS: There were 206 bronchoscopies, including 189 SBs and 17 CIBs, performed in 28 patients who underwent cadaveric lung transplantation between 2000 and 2013 at Osaka University Hospital. Among SBs, 92 (49%) showed positive results of transbronchial lung biopsy (TBLB) or bronchoalveolar lavage (BAL), and intervention was applied following 34 SBs (18%). Among CIBs, 8 (47%) showed positive results of TBLB or BAL, with intervention performed in 3 patients (18%). A2-3 and B2R findings according to the revised International Society for Heart and Lung Transplantation (ISHLT) rejection score and airway infection/colonization were frequently observed within a year following lung transplantation. Cytomegalovirus infection was found in 7 SBs (6%) by TBLB only within 2 months after transplantation. Regarding complications, moderate bleeding occurred in 21 (11%), pneumothorax in 2 (1%), prolonged hypoxemia in 1 (0.5%), and pneumonia in 1 (0.5%) among the 189 SBs. CONCLUSION: SB frequently detects rejection and airway infection or colonization with minimum complications, especially within 12 months after cadaveric lung transplantation.

Usefulness of the long-acting insulin analogue glargine in basal-bolus therapy for Japanese children and adolescents with type 1 diabetes mellitus.

The aim of this study was to evaluate the efficacy of long-acting insulin analogue glargine (G) changing from NPH in basal-bolus therapy for Japanese children and adolescents with type 1 diabetes mellitus (DM1). Thirty patients (11 M, 19 F) with DM1 aged 13.3 +/- 4.5 years were included in the study. Mean fasting blood glucose level was significantly decreased (baseline: 142.5 +/- 39.3 vs 127.1 +/- 24.0, 129.0 +/- 29.1, 121.1 +/- 26.0 mg/dl at 3, 6, 12 months, respectively, p <0.01), and mean HbA(1c) was significantly decreased (baseline: 8.06 +/- 0.85 vs 7.69 +/- 0.89, 7.57 +/- 0.93, 7.36 +/- 0.95%, at 3, 6, 12 months, respectively, p <0.01) after changing to G from NPH. Severe hypoglycemia rarely occurred during the study period. In conclusion, basal-bolus therapy using G resulted in improved overall glycemic control with a low risk of severe hypoglycemia in Japanese pediatric patients with DM1.

[Ball thrombus in the right atrium: report of a case].

A 63-year-old man visited our hospital because of intermittent claudication due to an embolic episode in the left femoral artery. He had a long history of arterial fibrillation but had received no anticoagulant therapy. Echocardiography showed a large floating ball-shaped shadow in the right atrium, without any sign of tricuspid stenosis. Pulmonary perfusion scintigram was normal. At the operation, the thrombus which attached to the superior atrial septum with a thin string was removed. The thrombus was 54 x 40 x 25 mm in size and 23.8 g in weight, whose cut surface was in layers. There was neither atrial septal defect nor foramen ovale to suggest possibility of paradoxical embolism. The postoperative course was uneventful and he was discharged on the 9th postoperative day. Although the mechanism of the thrombus formations is unknown, it is considered to be important to continue anticoagulant therapy to avoid reccurence of intracardiac thrombus.

[Thoracoabdominal aortic aneurysm combined with inferior mesenteric artery aneurysm and occlusion of celiac and superior mesenteric arteries].

A 56-year-old man with thoracoabdominal aortic aneurysm combined with inferior mesenteric artery aneurysm and occlusion of celiac and superior mesenteric arteries is presented. Contrast-enhanced computed tomography (CT) and aortography revealed thoracoabdominal aortic aneurysm of 6 cm in diameter, accompanied by inferior mesenteric aneurysm of 3 cm in diameter. Severe calcification of the abdominal aorta and occlusion of the celiac and the superior mesenteric arteries were also noted, whose territories were perfused by collateral circulation of the inferior mesenteric artery. At the operation, orifice of the left renal artery was stenosed by severe calcification, which was resected. Because of severe adhesion around the origins of celiac and superior mesenteric arteries, they were left unrevascularized. The thoracoabdominal aortic aneurysm was replaced with an Dacron tube graft, whose side branch was anastomosed to the inferior mesenteric artery after resection of its aneurysm. The postoperative course was uneventful, and no symptoms of intestinal ischemia were noted. As blood supply to the abdominal viscera mostly depends on the inferior mesenteric artery, careful follow-up is necessary.

[Persistent hyperplastic primary vitreous--a case report of adult onset acute angle-closure glaucoma].

BACKGROUND: We report a patient with persistent hyperplastic primary vitreous(PHPV) who presented with acute angle-closure glaucoma in his adult life. CASE: A 30-year-old man had an attack of acute angle-closure glaucoma associated with retrolenticular fibrous tissue, atrophic retina, and elongated cilliary process in his right eye. RESULT: Ultrasound biomicroscopy(UBM) study showed iris bowing, shallow anterior chamber, and elongated cilliary body which were being pulled by the retrolenticular mass. The posterior chamber was normal. CONCLUSION: Although the mechanisms of secondary angle-closure glaucoma in PHPV are complicated, we suspected pupillary block resulting from constriction by the retrolenticular mass in this case.

Changing predictors of postoperative mortality in acute type A aortic dissection. Is only coronary artery compromise significant?

OBJECTIVES: Rapid emergency transport and early diagnosis and surgical treatment for acute type A aortic dissection have improved postoperative survival, which has, however, plateaued at about 80%. End-organ malperfusion is regarded as a strong predictor of postoperative mortality, replacing factors such as cardiac tamponade complications, aortic rupture, and left ventricular dysfunction due to aortic insufficiency. It is thus important to reevaluate risk factors for surgical death to assess current therapeutic strategies. METHODS: We statistically analyzed potential risk factors for perioperative death in 88 patients undergoing surgical repair for type A aortic dissection between January 1990 and December 1999. RESULTS: Univariate analysis showed that cardiopulmonary arrest (adjusted odds ratio: 13.78; p < 0.01) and malperfusion of more than 1 vital organ (adjusted odds ratio 4.97, p < 0.01), especially myocardial ischemia due to coronary artery dissection (adjusted odds ratio 3.21, p < 0.05), significantly increased the likelihood of operative death. Multivariate logistic regression analysis showed only cardiopulmonary arrest (p < 0.01) and concomitant coronary artery bypass grafting necessitated in cases complicated by evolving myocardial infarction (p < 0.05) to be independent predictors of postoperative mortality. CONCLUSION: Preoperative complication from coronary dissection was the most important predictor of early postoperative mortality in this series. In such cases, rapid surgical intervention before myocardial infarction develops is vital to saving lives.

[An ultrasound biomicroscopic study of eyes after non-penetrating trabeculectomy].

PURPOSES: We studied the control of intraocular pressure(IOP) by various types of blebs after non-penetrating trabeculectomy(NPT) and the difference between bleb formation after penetrating trabeculectomy(PT) and that after NPT. METHODS: The filtering blebs of 45 yeys from 40 patients after NPT were studied using ultrasound biomicroscopy. They were grouped into four types, and the space under the scleral flap was classified into three types. The filtering blebs and the space under the scleral flap were correlated with IOP level. RESULTS: Overall, 40% of the blebs were L(low-reflective) type, 16% H(high-reflective) type, 16% E (encapsulated) type, and 29% F(flattened) type, but in good IOP control cases 59% of the blebs were L type, 14% H type, 14% E type, and 14% F type. L type blebs were found in 94% of eyes with good IOP control. CONCLUSION: Though filtering blebs of the L type could produce sufficient IOP reduction, blebs after NPT showed a greater tendency to become flattened than after PT. Additional systematic therapy must be designed to maintain the L type of filtering blebs after NPT.

Expression and localization of angiogenic inhibitory factor, chondromodulin-I, in adult rat eye.

PURPOSE: To determine the role in the eye of chondromodulin (ChM)-I, which has been identified in cartilage as an angiogenic inhibitor, the expression and localization and a possible function of ChM-I were investigated. METHODS: Expression and localization of ChM-I in rat eyes were examined by RNase protection assay and in situ hybridization and by immunostaining, using an antibody against a synthetic peptide. The effect of recombinant ChM-I on tube morphogenesis of retinal endothelial cells was examined in culture. RESULTS: The rat ChM-I gene was determined to encode the open reading frame of 334 amino acid residues, and ChM-I mRNA was exclusively expressed in cartilage, eye, and cerebellum in rats. ChM-I mRNA expression was evident in the iris-ciliary body, retina, and scleral compartments, but not in other compartments of the eye. In situ hybridization revealed mRNA expression in the ganglion cells, inner nuclear layer cells, and pigment epithelium in the retina and in the nonpigment epithelium of the ciliary body. Immunoreactive ChM-I was present in these cells and also in the vitreous body. Western blot analysis detected an approximately 25-kDa band of ChM-I presumed as a secretory form in the aqueous humor and vitreous body and an approximately 37-kDa band as a precursor form in the retina. Recombinant human ChM-I inhibited tube morphogenesis of human retinal endothelial cells in vitro. CONCLUSIONS: These observations indicate a potential role for ChM-I in inhibition of angiogenesis in the rat eye.

Mathematical and optimal clustering of test points of the central 30-degree visual field of glaucoma.

PURPOSE: To determine a mathematically optimal sector pattern of the central 30 degree visual field for the follow-up of glaucomatous visual field change based on a large number of actual visual field test data of patients with glaucoma. METHODS: Visual field test data obtained from 1,039 eyes of 1,039 patients with open-angle glaucoma (OAG) using the 30-2 program of the Humphrey Field Analyzer were used for sectorization of the central 30 degree visual field. Of the 1,039 visual field data, 698 (modeling data) were used for determining the sector pattern and 341 (testing data) for checking the sector pattern. The modeling data were further divided into three groups according to the mean deviation (MD) (MD > or = -10 dB, -20 < or = MD < -10 dB, and MD < -20 dB), and the sector pattern was constructed from visual field data of each group using a clustering procedure called VARCLUS. The testing data were used for determining the optimal sector pattern. In a separate set of repeated visual field data of 303 patients with OAG, the fluctuation of MD, sector values of each sector determined, and total deviation of each test point were calculated and compared. RESULTS: The sector pattern constructed from visual field data of MD > or = -10 dB summarized the visual field performance most effectively. The fluctuation of the sector value of each sector was roughly 1.5 times smaller than the total deviation of each test point. CONCLUSION: The sector pattern determined may be useful in analyses of the visual field data of patients with glaucoma.

Surgically treated Swyer-James syndrome.

Because patients with Swyer-James syndrome have almost always been treated conservatively, few reports exist of pathological findings of the lung in this syndrome. We report a case of this rare disease treated surgically and discuss pathological findings. A 36-year-old woman repeatedly contracted bronchitis and pneumothorax since adolescence, until April 26, 1997, when she reported chest pain and dyspnea. Chest X-ray on admission showed left pulmonary collapse with a slight deviation of the mediastinum toward the right. Chest computed tomography showed an apical bulla and emphysematous change in the left upper lobe. Pulmonary arteriography at age 17 showed hypoplasia of left pulmonary artery branches in the left upper lobe. Based on a diagnosis of Swyer-James syndrome, we conducted left upper lobectomy on May 2, 1997. Pathological examination of the resected left upper lobe showed marked emphysematous change, including an emphysematous bulla with destruction of alveolar structure and peribronchiolar fibrosis. No vascular abnormality was recognized in histology. Emphysematous change secondary to repeated bronchiolitis is believed to have led to her repeated pneumothorax.

Measurement of microcirculation in optic nerve head by laser speckle flowgraphy in normal volunteers.

PURPOSE: To report blood flow in the optic nerve head between the right and left eyes or the superior and inferior neuroretinal rims in normal volunteers using laser speckle flowgraphy. METHODS: This prospective study included 120 eyes of 60 normal volunteers (mean age, 50.0 +/- 16.9 years; range, 21 to 77 years). The square blur rate was measured by laser speckle flowgraphy (Kyushu Institute of Technology, Iizuka, Japan). The sequence of eye measurements was randomized. In each eye, measurements were taken at the neuroretinal rim away from visible vessels. Linear regression analysis, paired two-tailed t test, and two-way analysis of variance were used for statistical analysis. P values less than.05 were accepted as statistically significant. RESULTS: There was a significant correlation in square blur rate between the right and left eyes (r = 0.587, P <.001). Square blur rate in the superior temporal neuroretinal rim significantly correlated with that in the inferior temporal neuroretinal rim in each of the right (r = 0.546, P <.001) and left (r = 0.465, P <.001) eyes. Square blur rate in the right eye was higher than that in the left eye (P =.049). Square blur rate in the superior neuroretinal rim was higher than that in the inferior neuroretinal rim in both the right (P =.035) and left (P =. 005) eyes. CONCLUSION: There were statistically significant differences of optic nerve head blood flow in normal volunteers using laser speckle flowgraphy between the right and left eyes and between the superior and inferior temporal neuroretinal rims. These normal data can be used for understanding physiological ocular hemodynamics.

Measurement of microcirculation in the optic nerve head by laser speckle flowgraphy and scanning laser Doppler flowmetry.

PURPOSE: To evaluate and compare blood flow measurements by laser speckle flowgraphy and scanning laser Doppler flowmetry in the optic nerve head of normal volunteers. METHODS: This prospective study included 60 eyes of 60 normal volunteers (50.0 years; range, 21 to 77 years). Measurements were taken at the temporal neuroretinal rim away from visible vessels. The square blur rate, a quantitative index of relative blood velocity, was measured by laser speckle flowgraphy. Using scanning laser Doppler flowmetry, volume, flow, and velocity were measured at the same neuroretinal rim locations. RESULTS: The average square blur rate, volume, flow, and velocity were 7.11 +/- 1.65, 7.74 +/- 3.19, 151.85 +/- 70.63, and 0.53 +/- 0. 23 arbitrary units, respectively (n = 60). Square blur rate correlated significantly with flow and velocity (r =.361, P =.005; r =.359, P =.005, respectively). However, there was no significant correlation between square blur rate and volume (r =.101, P =.441). Although square blur rate decreased significantly with increasing age (r = -.375, P =.003), volume, flow, or velocity showed no significant correlation with age (r = -.249, P =.054; r = -.166, P =. 205; r = -.143, P =.275, respectively). Square blur rate also decreased significantly with mean blood pressure (r = -.315, P =. 014), but volume, flow, or velocity showed no significant correlation with mean blood pressure (r = -.159, P =.225; r = -.059, P =.654; r = -.043, P =.742, respectively). CONCLUSION: We found only a weak correlation between the blood flow indexes, as measured by laser speckle flowgraphy and scanning laser Doppler flowmetry because of basic differences in the principles of measurement.

Structure and chromosomal localization of the RAE28/HPH1 gene, a human homologue of the polyhomeotic gene.

The Polycomb group of (Pc-G) genes and trithorax group of genes are known to play a crucial role in the maintenance of the transcriptional repression state of Hox genes, probably through modification of the chromatin configuration. The rae28/mph1 gene is a mammalian homologue of the Drosophila polyhomeotic gene, which belongs to the Pc-G genes. As reported previously, we established mice deficient in the rae28/mph1 gene and showed that these homozygous animals displayed the developmental defects compatible with a human congenital disorder, CATCH22 syndrome. In this study we analyzed the structural organization of the human counterpart of the rae28/mph1 gene (RAE28/HPH1) and its processed pseudogene (psiPH), which are located on, respectively, human chromosome 12p13 and 12q13. The HPH1 gene consists of 15 exons spanning approximately 26 kb and its structural organization is well conserved between mouse and human. These genetic information of the RAE28/HPH1 gene may provide an important clue for further examination of its involvement in human congenital disorders related to CATCH22 syndrome.

Relationship between age and the thickness of the retinal nerve fiber layer in normal subjects.

PURPOSE: To determine it there are any age-dependent changes in the thickness of the retinal nerve fiber layer (RNFL) in the peripapillary area. METHODS: Sixty normal volunteers (31 men, 29 women) (120 eyes) whose ages ranged from 23-75 years (mean 48.4 years) participated in this study. The thickness of the RNFL was determined using a scanning laser polarimeter along the peripapillary area with a 1.75 disc diameter and along another ring 0.8 mm away from the disc margin. RESULTS: The thickness of the RNFL was not significantly correlated with age in either of the two ring areas. However, the RNFL thickness ratio of total/nasal area decreased significantly with increase in age in both rings. There was an increase in the difference of RNFL thickness between the right and left eyes of the same individual with aging, in both rings. CONCLUSIONS: It was suggested that the RNFL thickness determined along both rings demonstrated almost identically the relationship between age and RNFL thickness in normal subjects.

Measurement of retinal nerve fibre layer by scanning laser polarimetry and high pass resolution perimetry in normal tension glaucoma with relatively high or low intraocular pressure.

AIMS: To determine whether any differences may exist in the relation between the neural capacity as determined by high pass resolution perimetry and the thickness of the retinal nerve fibre layer (RNFL) in patients having normal tension glaucoma (NTG) with a relatively high intraocular pressure (IOP) between 16 and 21 mm Hg (HNTG) v those with a lower IOP below 15 mm Hg (LNTG). METHODS: Scanning laser polarimetry and high pass resolution perimetry were performed in 20 eyes of 20 patients with HNTG and 21 eyes of 21 patients with LNTG. The correlation between total and regional thickness of the peripapillary RNFL and the corresponding total and regional neural capacity with linear regression analysis were evaluated. RESULTS: Overall, although the total RNFL thickness was not significantly correlated with the total neural capacity, the RNFL thickness in each of the superior and inferior quadrants was significantly correlated with the corresponding regional neural capacity (r = 0.44, p = 0.0045; r = 0.39, p = 0.0126 for each). The RNFL thickness in each of the superior and inferior quadrants in the HNTG group was significantly correlated with the corresponding regional neural capacity (r = 0.52, p = 0.0196; r = 0.49, p = 0.0286 for each). No significant correlation between neural capacity and the RNFL thickness was observed either globally or regionally in the LNTG group. CONCLUSION: The degree of the correlation between neural capacity as determined by high pass resolution perimetry and thickness of the RNFL as measured by scanning laser polarimetry appeared to differ in NTG patients with an IOP higher than 15 mm Hg v those with a lower IOP.

The organization of the thalamostriatal projection from the lateral posterior thalamic nuclear complex (LP) in the pigmented rat.

We investigated the thalamostriatal projection of the rat using biotinylated dextran amine (BDA) and wheat-germ agglutinin horseradish peroxidase (WGA-HRP). To obtain the patch/matrix compartments of the striatum (ST), we used mu-opioid receptor (MOR) immunoreaction labeling. Thus, an MOR-positive 'patch' was indicated by a darkly stained spot, while the MOR-negative 'matrix' was displayed as a non-immunoreactive region. A small injection of BDA was made in a subregion of the lateral posterior thalamic nucleus (LP). The LP-ST fibers originated in all subregions of LP and terminated in the dorsocaudal portion of ST, where the corticostriatal fibers from the visual cortex terminate (Serizawa et al. 1994). These LP-ST fibers and terminals were concentrated in the MOR-negative matrix compartment. Electron microscopic observations showed that the LP-ST terminals made asymmetrical synaptic contacts mainly (70%, n = 30) with the dendritic spines of the presumptive ST-output neurons, and fewer (30%) contacted dendritic shafts. The present results provide anatomical support for the contention that ST-output spiny neurons of the matrix that project to the pars reticulata of the substantia nigra or globus pallidus, may be influenced directly by the LP-ST projection.

[A case of progressive saccular aneurysm caused by localized dissection of descending aorta].

A fifty-three-year-old man was admitted because of chest pain. CT scan showed the localized dissection of the descending aorta which was partially thrombosed. The patient was followed by controlling of essential hypertension. He, however, complained of the second attack of chest pain after a year and 5 months. CT scan showed the increased dilatation of the false lumen as compared to that of previous examination. MR angiogram showed a saccular aneurysm localized in the middle portion of the descending aorta. An operation was performed through posterolateral thoracotomy in the 4th intercostal space with the aid of normothermic femoro-femoral bypass circulation. The aneurysm was located at the level of 5th thoracic vertebra with the size of 70 mm in length and 45 mm in diameter. Entry was observed in the posterior wall of the aorta, and the terminal end of the false lumen was occluded with the organized thrombus. The aneurysm was successfully replaced with a prosthetic graft. To the extent of our knowledge, only limited surgical cases of saccular aneurysm caused by localized dissection of the middle portion of the descending aorta have been reported.