Search

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33-Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural necrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.

Hydrogel-based scaffolds have been widely used to fabricate artificial tissues capable of replacing tissues and organs. However, several challenges inherent in fabricating tissues of large size and complex morphology using such scaffolds while ensuring cell viability remain. To address this problem, we synthesized gelatin methacryloyl (GelMA) based bioink with cells for fabricating a scaffold with superior characteristics. The bioink was grafted onto a Z-stacking bioprinter that maintained the cells at physiological temperature during the printing process, without exerting any physical pressure on the cells. Various parameters, such as the bioink composition and light exposure time, were optimized. The printing accuracy of the scaffolds was evaluated using photorheological studies. The internal morphology of the scaffolds at different time points was analyzed using electron microscopy. The Z-stacked scaffolds were fabricated using high-speed printing, with the conditions optimized to achieve high model reproducibility. Stable adhesion and high proliferation of cells encapsulated within the scaffold were confirmed. We introduced various strategies to improve the accuracy and reproducibility of Z-stack GelMA bioprinting while ensuring that the scaffolds facilitated cell adhesion, encapsulation, and proliferation. Our results demonstrate the potential of the present method for various applications in tissue engineering.

Differential diagnosis of an intracardiac mass is difficult when detected only by echocardiography before a biopsy is completed. However, treatment cannot be postponed until the biopsy results are obtained. We report the case of a 12-year-old girl who presented with an intracardiac mass in the mitral valve mimicking infective endocarditis and severe mitral regurgitation. The mass was finally diagnosed as valvulitis associated with systemic juvenile idiopathic arthritis, which was complicated with macrophage activation syndrome. After careful exclusion of acute infectious disease, we started steroid pulse therapy and administered tocilizumab to treat the cytokine storm before performing the surgery. Finally, we performed mass excision and mitral valve replacement after immunosuppressant therapy.

We reviewed the anatomical characteristics of the conduction system in the ventricles of human and ungulate hearts and then raised some questions to be answered by clinical and anatomical studies in the future. The ventricular conduction system is a 3-dimensional structure as compared to the 2-dimensional character of the atrial conduction system. The proximal part consisting of the atrioventricular node, the bundle of His and fascicles are groups of conducting cells surrounded by fibrous connective tissue so as to insulate from the underlying myocardium. Their location and morphological characters are well established. The bundle of His is a cord like structure but the left and right fascicles are broad at the proximal and branching at the distal part. The more distal part of fascicles and Purkinje system are linear networks of conducting cells at the immediate subendocardium but the intra-mural network is detected at the inner half of the ventricular wall. The papillary muscle also harbors Purkinje system not in the deeper part. It is hard to recognize histologically in human hearts but conducting cells as well as Purkinje cells are easily recognized in ungulate hearts. Further observation on human and ungulate hearts with myocardial infarct, we could find preserved Purkinje system at the subendocardium in contrast to the damaged system at the deeper myocardium. Further studies are necessary on the anatomical characteristics of this peripheral conduction system so as to correlate the clinical data on hearts with ventricular arrhythmias.

Background Adults with unoperated congenitally corrected transposition of the great arteries are rare but form a distinct group among adults with congenital heart disease. Patients with congenitally corrected transposition of the great arteries often have one or more associated cardiac anomalies that dictate the need for, and timing of, surgical intervention in childhood. However, in a proportion of patients, the hemodynamics does not require surgical attention during childhood, and, in some patients, a correct diagnosis is not established until adulthood. Here we report an adult case of unoperated congenitally corrected transposition of the great arteries with a large ventricular septal defect and probable pulmonary arterial hypertension. Case presentation Our patient was a 46-year-old Korean man. Transthoracic echocardiography and cardiac catheterization demonstrated hemodynamically balanced ventricles with a non-regurgitant systemic atrioventricular valve, normal pulmonary arterial pressure, and a reasonable difference between the oxygen saturation values of the aorta and pulmonary trunk, even with the presence of a large ventricular septal defect. Further morphological assessments using cardiac computed tomography and three-dimensional modeling/printing of his heart revealed that the mitral valve was straddling over the posteriorly positioned ventricular septal defect, which could explain the functional and anatomical subvalvular pulmonary stenosis and a small amount of shunt flow through the large ventricular septal defect. We interpreted this combination of cardiac defects as able to sustain his stable cardiac function. Thus, we decided to maintain his unoperated status. Conclusion A detailed anatomical understanding based on transthoracic echocardiography, cardiac computed tomography, and three-dimensional printing can justify a decision to not operate in cases of congenitally corrected transposition of the great arteries with hemodynamically balanced pulmonary stenosis and a ventricular septal defect, as observed in the present case. Electronic supplementary material The online version of this article (10.1186/s13256-019-2145-1) contains supplementary material, which is available to authorized users.

The Palsangjeon Pagoda is a five-story wooden building in the Beopjusa Temple area in the Songnisan national park in Chungcheongbuk-do, Korea. According to historical records, it was constructed in either AD 1605 or AD 1626. To specify the construction year more precisely, we took 41 wood samples for tree-ring analysis during repair actions in 2013; 28 from red pine (Pinus densiflora S. et Z.), 12 from oak (Quercus spp.), and 1 from fir (Abies spp.). The tree-ring boundaries became clearly visible by smoothing their cross-sectional surface and the tree-ring widths were measured under a stereo microscope. All tree-ring series were compared with each other to establish mean chronologies, which we then compared with local master chronologies established using tree rings collected from wooden elements of the Daeungjeon Hall which is the main building in the Beopjusa Temple area. As a result, it was verified that the red pines were felled in AD 1624 and in AD 1851. Moreover, it was verified that the oaks were also felled in AD 1624 based on cross-dating with the red pine chronology. We concluded that the Palsangjeon Wooden Pagoda was constructed in AD 1626, as mentioned in the historical record (Daeungdaekwangmyeongjeonbulsangki, 1630) and the letters on a purlin on the 4th story, using oak and red pine felled in AD 1624 and repaired later on using red pine felled in AD 1851.

Background Although ganglionated plexi (GPs) are important in the pathogenesis of arrhythmia, their patterns of atrial innervation have remained unclear. We investigated patterns of GP innervation to cardiac atria and the neuroanatomical interconnections among GPs in an animal model. Methods Atrial innervation by GPs was evaluated in 10 mongrel dogs using a retrograde neuronal tracer (cholera toxin subunit B [CTB] conjugated with fluorescent dyes). In Experiment 1, CTB was injected into the atria. In Experiment 2, CTB was injected into the major GP, including the anterior right GP (ARGP), inferior right GP (IRGP), superior left GP (SLGP), and ligament of Marshall (LOM). After 7 days, the GPs were examined for the presence of tracer-positive neurons. Results GPs in either right or left-side were innervating to both the same and opposite sides of the atrium. In quantitative analysis, right-sided GPs, especially ARGP, showed numerical predominance in atrial innervation. Based on the proportion of CTB-labeled ganglion in each GP, atrial innervation by GPs showed a tendency of laterality. In Experiment 2, CTB that was injected to a particular GP widely distributed in different GP. ARGP projected the largest number of innervating neurons to the IRGP, SLGP and LOM. Conclusion This study demonstrated that GPs project axons widely to both the same and opposite sides of atria. ARGP played a dominant role in atrial innervation. Furthermore, there were numerous neuroanatomical interconnections among GPs. These findings about neuronal innervation and interconnections of GPs could offer useful information for understanding intrinsic cardiac nervous system neuroanatomy.

Lung cancer is the leading cause of cancer-related death in Korea, accounting for approximately 20% of all cancer deaths [1]. Non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers, and the majority of patients with NSCLC present at an advanced cancer stage (stage III or IV) [2]. In the last decade, several studies have been performed on the molecular stratification of NSCLC in order to provide targeted treatment based on activating or driver mutations in these tumors. Activating mutations in the epidermal growth factor receptor gene (EGFR) can be used as therapeutic targets for treatment of NSCLC. In the Iressa Pan-Asia Study, tumors with EGFR mutations showed a 71.2% clinical response to first-line treatment with gefitinib, while tumors with wild-type EGFR showed only a 1.1% response [3]. Since then, several randomized control studies have shown an association between activating EGFR mutation and response to EGFR tyrosine kinase inhibitors (TKIs) [4-9]. Patient selection is important for using EGFR TKIs as the first-line treatment. At present, analysis of EGFR mutations is the accepted method for identifying patient response to EGFR TKIs. Direct DNA sequencing is a standard method for identifying mutations and is commonly used in the Asia-Pacific region [10]. Any routinely available pathological specimen can be used for analyzing EGFR mutations, including formalin-fixed, paraffin-embedded tissues from surgical resections; small tissue biopsies; or cell block preparations. Several publications have reported the prevalence of EGFR mutations in patients with NSCLC [10-14]. The rates of EGFR mutations are higher in Asian countries than in Western countries. Further, rates of EGFR mutations in Korean patients range from 17.4% to 51.3% [10,15-22]. Therefore, we performed a nationwide study of EGFR mutations in Korean patients with NSCLC in order to provide reliable information on the incidence and characteristics of EGFR mutations. This study was led by the Korean Cardiopulmonary Pathology Study Group.

Background Atrial fibrillation (AF) in adult patients with atrial septal defect (ASD) accompanies an enlarged right atrium (RA) with a less enlarged left atrium (LA), which is the opposite situation in patients with AF and mitral valvular disease. This study was to compare the histopathological change in the atrium of patients with AF of two different etiologies: ASD and mitral disease. Methods Twenty-four patients were enrolled. Group 1 included patients with ASD (8), Group 2 included patients with ASD with AF (6), and Group 3 included patients with mitral disease with AF (10). Preoperative atrial volumes were measured. Atrial tissues were obtained during surgical procedures and stained with periodic acid-Schiff, smooth muscle actin, Sirius red, and Masson’s trichrome to detect histopathologic changes compatible with AF. The severity of histopathological changes was represented with “positivity” and “strong positivity” after analyzing digitalized images of the staining. We investigated the relationship between the degree of atrial dilatation and severity of histopathological changes according to the groups and tissues. Results Group 2 and Group 3 patients showed a tendency toward an enlarged RA volume and enlarged LA volume, respectively, compared with each others. However, in the histopathologic analysis, “positivity” and “strong positivity” showed no significant positive correlations with the degree of atrial volume in special staining. Conclusions A similar degree of histopathologic changes was observed in both atria in patients with AF (Group 2 and 3) regardless of the degree of dilatation of atrial volume and disease entities.

The existence of myofibroblasts (MFBs) and the role of subendocardial smooth muscle (SSM) layer of human atrial tissue in atrial fibrillation (AF) have not yet been elucidated. We hypothesized that the SSM layer and MFB play some roles in atrial structural remodeling and maintenance of valvular AF in patients who undergo cardiac surgery.We analyzed immunohistochemical staining of left atrial (LA) appendage tissues taken from 17 patients with AF and 15 patients remaining in sinus rhythm (SR) who underwent cardiac surgery (male 50.0%, 54.1 ± 14.2 years old, valve surgery 87.5%). SSM was quantified by α-smooth muscle actin (α-SMA) stain excluding vascular structure. MFB was defined as α-SMA+ cells with disorganized Connexin 43-positive gap junctions in Sirius red-positive fibrotic area.The SSM layer of atrium was significantly thicker in patients with AF than in those with SR (P=.0091). Patients with SSM layer ≥ 14 μm had a larger LA size (P=.0006) and greater fibrotic area (P=.0094) than those patients whose SSM layer14 μm. MFBs were found in 7 of 17 (41.2%) patients with AF and 2 of 15 (13.3%) in SR group (P=.0456) in SSM area, colocalized with Periodic Acid-Schiff (PAS) stain-positive glycogen storage cells (95.5%).SSM layer was closely related to the existence of AF, degrees of atrial remodeling, and fibrosis in patients who underwent open heart surgery. We found that MFB does exist in SSM layer of human atrial tissue co-localized with PAS-positive cells.

MicroRNA (miRNA) has a critical effect on tumorigenesis through post-transcriptional modification and is considered to be potential biomarkers for cancer diagnosis and treatment monitoring. We evaluated the expression pattern of three selected miRNAs (miR-21, miR-155, and let-7a) to evaluate their potential roles by quantitative reverse transcription-polymerase chain reaction using formalin-fixed and paraffin-embedded tissues of 63 surgically resected pulmonary neuroendocrine (NE) tumors (19 typical carcinoids (TCs), 6 atypical carcinoids (ACs), 19 large cell NE carcinomas (LCNECs), and 19 small cell lung carcinomas (SCLCs). Control amplification for U6 small nuclear RNA (U6) was performed in all samples. Normalized Ct values were calculated (CtExperimental miRNA-CtU6) for each case and recorded. The expression levels of miR-21 and miR-155 were significantly higher in high-grade NE carcinomas (LCNECs and SCLCs) than in carcinoid tumors (TCs and ACs) (each P < 0.001). The expression level of miR-21 in carcinoid tumors with lymph node metastasis was significantly higher than in carcinoid tumors without lymph node metastasis (P= 0.010). To the best of our knowledge, the present study is the first to examine the expression patterns of miR-21 and miR-155 as an adjunctive diagnostic tool or clinically relevant biomarkers for pulmonary NE tumors.

Aims Additional linear ablation lesions are created to improve the outcomes of pulmonary vein (PV) isolation during atrial fibrillation (AF) ablation. We aimed to evaluate the safety and feasibility of additional ablation sites in terms of anatomical characteristics. Methods and results Multi-detector computed tomography (MDCT) data from 140 consecutive patients (40 with AF, 84 males, 59 ± 11 years old) and additional 10 heart specimens were analysed for their anatomical characteristics at three types of mitral isthmus lines: anteromedial (AM), anterolateral (AL), and posterolateral (PL) lines (from right superior, left superior, and left inferior PV to 10, 12, and 4 o'clock position of the mitral annulus, respectively). The data demonstrated that the length was shortest at the PL lines (MDCT, 36.4 ± 8.6 mm; specimens, 31 ± 6 mm) and the maximal myocardial thickness was greatest at the AL lines (MDCT, 3.2 ± 1.0 mm; specimens, 5.0 ± 0.9 mm). Ridge, cord-like structure, or diverticulum was found most frequently at the AM lines (MDCT, 20%; specimens, 20%). Sinus nodal artery (SNA) was found near the AM (MDCT, 100%; specimens, 90%) and AL lines (MDCT, 46.3%; specimens, 30%), while left coronary artery (LCA) and cardiac vein were closest to the PL lines. The trend of these findings was not significantly altered with the presence of AF. Conclusions The PL lines were shortest among the three mitral isthmus lines, but closest to LCA. Myocardium was thickest at the AL line, and SNAs were frequently found on the anterior lines. Multi-detector computed tomography provided detailed information, and further studies are required to clarify the clinical impact of these findings.

Structured abstract Objectives The "lower versus upper leg saphenous vein (SV) composite graft based on the left internal thoracic artery (ITA) for coronary artery bypass grafting" trial was designed to compare the histologic, immunohistochemical and angiographic findings of lower versus upper leg SV composite grafts. Methods Twenty-six patients with multi-vessel coronary artery disease were prospectively randomized to undergo revascularization using a lower leg (group LLV, n =13) or upper leg (group ULV, n =13) SV composite graft based on the in situ left ITA. The SV was harvested with a "no-touch" technique, and two excess segments were removed from the distal and proximal portions of each SV conduit. Another proximal segment was removed from the reversed SV composite graft, which had been dilated by the native ITA pressure. Hematoxylin-eosin staining, immunohistochemistry, and early and 1-year postoperative angiographic results were compared. Results The histologic study showed that the proximal and dilated proximal SV conduit lumen diameters were smaller in group LLV than in group ULV (proximal, 623±143 μm vs. 858±266 μm, P =0.008; dilated proximal, 1138±419 μm vs. 1477±353 μm, P =0.047). However, there were no differences in the lumen diameters of the distal SV segments in terms of immunohistochemical comparisons, diameters, patency rates, or filling frame counts of the SV conduits on early and 1-year postoperative angiograms between the two groups. Conclusions Although the proximal segment luminal diameters were smaller in the lower leg SV, there were no differences in the immunohistochemical results or patency rates on early and 1-year postoperative angiograms between the lower and upper leg "no-touch" SV conduits.

This paper reports the results of tree-ring dating and accelerator mass spectrometry (AMS) wiggle-matching for wooden Buddhist statues stored at the Eungjindang Hall of Neunggasa Temple, South Korea. Among 23 statues, 10 were successfully dated by tree rings. The cutting date of logs used for the statues was determined as some time between late fall 1684 and early spring 1685 when the bark ring (AD 1684) completed latewood formation. The 95.4% confidence interval of a radiocarbon date (cal AD 1688–1713, 2 σ), which was obtained by wiggle-matching 7 samples of a statue, is similar to the dendro-date (AD 1684). A historical document recorded that the statues in the Eungjindang of Neunggasa were dedicated in July 1685. The dendro-date and written record indicate that Eungjindang statues were made within 3–8 months after log cutting. This seems rather short if we consider the period required for natural drying to avoid defects such as cracking and crooking.

We report a case of bilateral pulmonary agenesis (BPA), which was suspected during a prenatal US examination and diagnosed by fetal magnetic resonance imaging (MRI). BPA is an extremely rare congenital anomaly and, although many fetal structural defects can be detected with a high degree of confidence after introducing high-resolution US, the prenatal diagnosis of BPA remains problematic. Other thoracic abnormalities, such as a congenital diaphragmatic hernia, congenital cystic adenomatoid malformation, and pulmonary sequestration, should be excluded from the list of possible diagnoses before coming to the conclusion of BPA, because BPA is absolutely incompatible with extrauterine life, and an accurate internal diagnosis can prevent a futile intervention from being performed.

Sudden unexpected deaths due to cardiovascular diseases make up almost half of all natural deaths. Practical guidelines are needed for forensic autopsy practice in cases of natural unexpected deaths due to ischemic heart disease or other cardiovascular diseases in Korea. An evaluation of the clinical history is the first step, including the collection of all available information on the subject. As a standard autopsy procedure, every subsystem of the heart and vessels should be thoroughly studied including the coronary arteries, the myocardium, the cardiac valves, and the conducting system. In addition, histological, toxicological, biochemical and molecular analysis need to be applied to the detection of myocardial infarction from the medico-legal point of view. Also important is the assessment of risk factors for natural unexpected cardiac death (NUCD) in order to establish a cause–effect relationship. There are three groups of ischemic conditions of heart leading to NUCD, those being acute myocardial infarction, atherosclerotic heart disease and critical coronary atherosclerosis. Additionally, there are practical concerns on formulating the report. Pathologists may use sudden cardiac death or NUCD as a main diagnosis when there is no alternative diagnosis, though they would do better to comment on conditions contributing to the death. Finally, pathologists should be encouraged to suspect unexplained causes of death in order to find clearer answers.

Background and aims: The systemic effects associated with mechanical ventilation of lungs injured by hydrochloric acid (HCl) aspiration are unexplored. We hypothesize that low dose acid aspiration will predispose the lung and the kidney to damage from large tidal volumes through activation of inducible nitric oxide synthase (iNOS). Materials and methods: Hydrochloric acid (HCl; pH 1.25, 1 mL/kg), or an equal amount of 0.9% sodium chloride (NaCl), were inserted into the trachea of rats immediately prior to mechanical ventilation. Rats were then ventilated with room air at 85 breaths per minute for 2 hours, either with a tidal volume (VT) of 7 mL/kg or 14 mL/kg (VT7, VT14) and zero end expiratory pressure. Kidney microvascular leak, which was assessed by measuring urine protein over 24 hours and by Evans blue dye (EBD) technique, was used as an indicator of systemic microvascular leak. Results: A significant microvascular leak occurred in both lung and kidney exposed to VT14 with HCl compared to those exposed to either VT7 with HCl or the NaCl control group. iNOS activity was significantly increased in the lung and the kidney tissue in VT14 with acid aspiration. The relatively selective iNOS inhibitor, l-N6-(1-iminoethyl)lysine (l-NIL), attenuated the EBD microvascular leak in lung and kidney and the proteinuria in the VT14 with acid aspiration group. Conclusion: iNOS may have mediated the systemic microvascular leak in the present model.

Introduction: the cause of thromboangiitis obliterans (TAO) still remains unknown. We have reported that immunologic injury associated with T lymphocytes infiltration might be the initial etiologic mechanism in TAO. The present study was undertaken to examine further the mechanism of immune injury. Methods: arterial walls affected by TAO were obtained from eight patients with eight non-pulsatile arteries and one patent artery. Immunohistochemical and TUNEL studies were performed for phenotyping of the infiltrating cells with CD4 (helper T cell), CD8 (cytotoxic T cell), CD56 (natural killer cell), and CD68 (macrophage), for identification of cell activation with VCAM-1 and i -NOS, for the presence of cell death with TUNEL analysis, and for inflammatory cytokine detection with RT-PCR. Results: the characteristic features were luminal obliteration, together with a varying degree of recanalization. T cells infiltrated mainly in thrombus, intima, and adventita. Among infiltrating cells, CD4 T cells greatly outnumbered CD8 cells. VCAM-1 and i -NOS were expressed in endothelial cells around the intima (patent segment) or vaso vasorum (occluded segment). Endothelial cells in vaso vasorum stained positive with TUNEL. Interferon-γ mRNA was detected in two specimens. Conclusions: our results suggest that T cell mediated immune inflammation is a significant event in the development of TAO. Eur J Vasc Endovasc Surg 25 , 451-457 (2003)

A 12-day-old female baby underwent a Norwood procedure for hypoplastic left heart syndrome. The left superior vena cava (LSVC), which was found incidentally during the operation, was divided to facilitate surgical exposure. After the operation, she developed signs of low cardiac output and died 7 hours afterward. Autopsy findings showed that the coronary sinus was atretic at the orifice without unroofing into both atria, rendering the LSVC the sole route of coronary sinus drainage. In patients with incidentally-found LSVC during surgery, special care should be taken to leave the LSVC intact because the LSVC may be the exclusive drainage vein of the coronary venous system. (Korean J Thorac Cardiovasc Surg 2010;43:161-163)

Abstract —To verify that apoptosis is one of the possible mechanisms of neonatal vascular remodeling during the transition from fetal to neonatal circulation, we assayed for apoptosis and evaluated the expression of apoptosis-regulatory proteins in umbilical vessel versus ascending aorta, ductus arteriosus (DA) versus adjacent pulmonary artery and aorta, or aorta versus its branching arteries. Twenty-two umbilical cords (UCs), 6 DAs with adjacent aortas and pulmonary arteries, and 4 aortic arches with their branching great arteries were obtained from neonates. Smooth muscle cell (SMC) apoptosis in umbilical vessels was identified in all UCs. The expressions of Bax and Bcl-X were stronger in umbilical artery than in the neonatal aorta, but Bcl-2 was weak in both arteries in immunohistochemistry. In the immunoblot analysis of UCs, the expression of the proapoptotic short isoform of Bcl-X was stronger than in other tissue, and caspase-3 was selectively activated, whereas it was not in the other components of the cardiovascular system. In contrast, the expression patterns of the FasAg and Fas ligand were similar in umbilical artery and aorta. Regulation of Bcl-2 family proteins was also observed in other vascular sites at which SMCs undergo apoptosis on hemodynamic changes during birth, such as the DA and the branching points of the great arteries from the aortic arch. Apoptosis is involved in the regression of human umbilical vessels and the DA and in the remodeling of the branching great arteries during the neonatal period, when Bcl-2 family proteins are likely to play a key role.

OBJECTIVE: The objective of our study was to analyze MR images of vascular leiomyoma of the extremity and to compare these images with histopathologic findings to determine if a correlation exists. CONCLUSION: T2-weighted MR images of vascular leiomyoma of an extremity showed a mass with mixed areas that were both hyper- and isointense to skeletal muscle and also revealed a hypointense rim; these images correlate with histopathologic findings of smooth muscle, vessels, fibrous tissue, an intravascular thrombus, and a fibrous capsule.

Pulmonary atresia with intact ventricular septum (PAIVS) is a rare congenital cardiac anomaly that has been classified into two types: one is a more frequent type having dysplasia of tricuspid valve (TV) with a small annulus, underdeveloped right ventricle (RV) with a hypoplastic cavity and a hypertrophic wall; the other type has severe dysplasia of TV and dilatation of RV, right atrium (RA), and right atrioventricular junction with thinning of the RV wall. We performed a morphologic study on 11 autopsied hearts with PAIVS, giving particular emphasis to the variation of morphology of the TV. We could classify these hearts into 3 groups according to the degree of right ventricular development. In the first group of 7 cases (type I), the RVs were underdeveloped. Thick leaflets, restricted valve apparatus with short chordae, and small annuli were characteristics of the TV. In the second group of 3 cases (type II), the RVs showed marked enlargement of the cavity and thinning of the wall. The TV showed redundant, dysplastic, sail-like anterior leaflets, and the downward displacement of septal leaflet and/or posterior leaflet, which are the findings frequently observed in Ebstein's malformation. The RVs were dilated and with partially unguarded tricuspid orifice. The septal leaflet of the TV was dysplastic and, in two cases, the septal leaflet showed chordal structure at the upper surface facing the RA, which is a peculiar finding that has not been described in the literature. The remaining case was a heart with a moderately developed RV (type III). The TV showed mildly dysplastic appearance and we classify this as a separate type, because we could expect the best surgical results in this type. This type had optimal size of RV and the mildest degree of dysplasia of TV. In PAIVS, the morphology of TV correlates well with the type of the right ventricular development.

Each of the two minimally united livers of thoracopagus conjoined twins occupied an epigastrium on opposite aspects of the conjoined abdomen, straddling the plane of conjunction, instead of being located beneath the domes of the diaphragm. Whereas the hepatic artery and portal vein of the right twin supplied only the larger “anterior” liver, the same vessels in the left twin divided to provide blood for both the “anterior” and the “posterior” liver. Thus the “posterior” liver had only one porta hepatis while the “anterior” liver had two. In addition, the hepatic veins of both ectopic livers were found to drain into the inferior vena cava of only the left twin. All of these anomalies have been reported, albeit rarely, among 477 cases of thoracopagus and omphalopagus twins recently reviewed. A theory explaining the abnormal embryology of the liver is proposed.

Background The cranial base is not only an end result of complex segmental growth of rostral end of axial skeleton but also has a tremendous impact on the development of the brain and facial structure. However, little is known about the method for the systematic analysis of the shape of the cranial base in the developing human fetus. We used roentgenograms of the cranial base and eviscerated bones for the assessment of the development of the cranial bony complex. Methods The cranial base was removed from 64 normal human fetuses after 18–40 weeks of gestation. Roentgenograms were taken perpendicular to the cranial base. Major anatomical landmarks are defined as follows: the center of pituitary fossa of sphenoid bone (point S), the growth center of zygomatic bone, the anterior point of nasal septum, otic cartilage, and anterior and posterior growth centers of maxilla. The anterior cranial base angle, the middle cranial base angle, the posterior cranial base angle, the maxillary trapezoid area, the horizontal middle face area, and the occipital cranial base triangle area are defined from the landmarks, and the growth of each parameter was analyzed by gestational age. Results The proportional growth of the anterior, middle, and posterior cranial fossae could be assessed by the angles around the center of the pituitary fossa (point S) and by the anterior, middle, and posterior cranial base angles. The anterior cranial base angle was relatively constant during the fetal period at 107.4–112.5°, whereas the middle cranial base angle gradually increased, and the posterior cranial base angle decreased. With increasing gestational age, the horizontal middle face area increased rapidly, in contrast to those of the maxillary trapezoid area, occipital cranial base triangle area, or foramen magnum area. Conclusions The important keys in the structural development of the normal human cranial base are anterior, middle, and posterior cranial base angles. We could define the developmental pattern of human cranial base, which in turn provides a model of a standard growth pattern applicable to the study of the different malformations in the craniofacial structure. © 1996 Wiley-Liss, Inc.

Summary Background There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma. Objective This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histologicai abnormalities in asthmatics according to the severity ot asthma. Methods Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and eosinophils in BALF were significantly increased in asthmatics and showed significant correlations with PC20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inllammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultra-structural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickeness of basal lamina. Conclusion These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.

We have experienced 7 cases of giant lymph node hyperplasia in the chest from 1981 to 1992. The ages of the 1 male and 6 female patients ranged from 9.9 to 40.4 years (mean age, 29.2 +/- 10.4 years). In 4 patients, a mass was discovered in routine radiographs. Focal calcification suggesting continual enlargement over a long time was noted in 1 patient. The sites of lesions were unusual in 2 patients (intercostal space and intrapulmonary fissure). All patients underwent surgical removal of the mass. Five cases had typical features of the hyaline-vascular type, and 2 cases revealed a mixture of the hyaline-vascular type and the plasma-cell type. Follow-up was available in all patients (mean follow-up, 31.9 months). In 1 patient, recurrence was observed 9 years after surgical removal. In general, giant lymph node hyperplasia can occur anywhere in the chest, grow without symptoms, and recur in spite of complete resection. Surgical resection and close follow-up are advised.

An echocardiographic study was performed on seven patients with twisted atrioventricular connections (criss-cross heart) relative to the usual atrial arrangement. The atrioventricular connections were concordant in five patients and discordant in two. The ventriculoarterial junction was either doubleoutlet right ventricle (n = 6) or discordant connections (n = 1). Associated cardiac defects were ventricular septal defect (n = 7), pulmonary stenosis (n = 5), straddling tricuspid valve (n = 2), and straddling mitral valve (n = 1). Malalignment between the atrial and ventricular septum was the most important feature of this disease and resulted in altered spatial orientation of the trabecular ventricular septum, and recesses in the ventricles and the right atrium. When assessed by echocardiography, these anatomical features were not invariably recognized in every case, but they were dependent upon the type of atrioventricular connections and the presence of straddling of the atrioventricular valves. Left ventricular recess was the most consistent feature and was present in every patient, regardless of the atrioventricular connections. Right atrial recess was found in four of five patients with concordant atrioventricular connections but was not present in patients with discordant atrioventricular connections. Right ventricular recess was recognized as such in a single patient with concordant atrioventricular connection and straddling mitral valve. The trabecular septum was oriented in a horizontal plane in hearts with concordant atrioventricular connections and without atrioventricular valve straddling. The trabecular septum was oriented semivertically in all other hearts. Echocardiography is a reliable diagnostic tool, not only for making a diagnosis of twisted atrioventricular connections but also for identifying altered orientation of the ventricular septum and abnormal recesses in the left ventricle and the right atrium.

A variety of experiments of endothelial cell seeding on artificial vessels have been performed. To improve endothelialization, one or two extracellular matrix components have been used as an underlying matrix. Although these methods have succeeded in in vitro experiments, they have not performed well in vivo. In this study, the authors used the whole extracellular matrix (ECM) excreted from fibroblasts as an underlying matrix. Fetal human fibroblasts were cultured on a polyurethane (PU) sheet. After confluence was attained, the cytoskeleton and the nuclei of the fibroblasts were destroyed using Triton-X, mitomycin, and irradiation. Omental microvascular endothelial cells from adult humans were seeded on various supports. After 12 days in culture, the cells were counted. The authors found that the ECM treated by irradiation had the highest cell number. In addition, the cells on this support exhibited the best morphologic appearance. Finally, the authors performed preliminary animal experiments. The PU vessels (inner diameter: 1.5 mm) treated with ECM were implanted in the arteries of rats. After the vessels had been implanted for 5 weeks, the authors found that the surface of the PU vessels were completely covered with endothelial cells. On the basis of these results, the authors conclude that the whole ECM makes a better underlying substrate for the endothelialization of small diameter artificial vessels.

The morphological variation in the recognized landmarks for the atrioventricular conduction system was studied grossly in 94 hearts with atrioventricular septal defect, assessing 20 hearts with normal atrioventricular septation as a control. In all the hearts with intact atrioventricular septal structures, the tendon of Todaro demarcated the superior boundary of the triangle of Koch. In hearts with atrioventricular septal defect, however, the landmarks for the conduction axis made up a separate nodal triangle. The tendon of Todaro, along with a bridging tendon not found in the normal heart, were variably developed in hearts with atrioventricular septal defect and formed a further triangle unrelated to the axis for atrioventricular conduction. The opening of the coronary sinus was also variable in its location and size. It was the location of the inferior bridging leaflet as it crossed the ventricular septum that was the best surgical landmark to the site of penetration of the atrioventricular conduction axis.

We studied the postmortem vascular anatomy of four patients with total anomalous pulmonary venous connection (TAPVC) with obstruction using a silicone rubber casting method. Two patients were studied clinically but died before therapeutic intervention, one died after corrective surgery, and another was not diagnosed before death. The morphologic types were supracardiac (2), infracardiac (1), and mixed (1). One of the supracardiac forms had a stenosis at the left vertical vein by a bronchoarterial vise, and a collateral channel to the right superior caval vein was also present. In the other supracardiac case, a left upper pulmonary vein was connected to the left vertical vein above the stenotic portion, resulting in postoperative pulmonary hemorrhage into the left upper lobe. The patient with infracardiac TAPVC had a tree-shaped descending vertical vein and small opening at the inferior caval vein. In the mixed type, a right upper pulmonary vein ran between the pulmonary artery and bronchus draining into the superior caval vein, and the rest of the drainage was to the portal vein.

Mucous gland adenoma of the bronchus is a truly benign, well defined, intraluminal mass that manifests on CT with air-meniscus sign or abutting the bronchus. We report the CT findings of mucous gland adenoma in two patients.

This study was performed to evaluate the clinical feasibility of use of immunologically nontreated xenogenic valves, using a porcine-to-goat pulmonary valved conduit implantation model. Porcine pulmonary valve conduits were prepared with no specific immunological treatment and implanted in the right ventricular outflow tract of goats under cardiopulmonary bypass. The goats were assigned at predetermined intervals (1 day, 1 week, and 3, 6, and 12 months) as two animals for each interval. Echocardiographic examinations of the valves were performed before sacrifice. Upon retrieving the xenograft specimens, they were inspected visually and microscopically. Ten of the 12 animals survived the predetermined observation periods. Variable degrees of pulmonary regurgitation were the main findings on echocardiographic evaluations. On gross examination of the explanted specimens, all leaflets, except in one animal that prematurely died, were fairly well preserved. They were slightly shortened but free of thrombosis or vegetation. Aneurysmal dilatations of the anterior wall of the implanted pulmonary artery were observed in one of 12-month-survival animals and in another one of 3-month-survival animals. Microscopically, the three components of implanted xenografts (the pulmonary artery, valve, and infundibulum) were shown to be gradually replaced with host cells in time, while maintaining structural integrity. The nuclei of the donor tissue disappeared through pyknosis and karyolysis. In conclusion, immnunologically untreated xenogenic pulmonary valved conduits can be an alternative potential as valve substitutes with distinctive advantages of providing self-healing potential, despite a few problems observed in the current study such as occurrences of pulmonary regurgitation and sporadic cases of aortic aneurysm.

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent. Graphical Abstract

An experiment to study the role of contact-activation leukocyte sequestration in the formation of ischaemia-reperfusion injury (I-R injury) was carried out. The study was conducted using light and electron microscopic analyses in an ovine cardiopulmonary bypass (CPB) model using a membrane oxygenator. Five adult sheep were used in the study. The CPB circuitry consisted of a roller pump and a membrane oxygenator. During CPB, flow rates ranged from 50 to 60 ml/kg/min with mild hypothermia. The CPB time was fixed at 120 min. Ten minutes after the start of CPB, total CPB was established. Thereafter, total CPB was performed for 100 min, followed by another 10 min of partial CPB. Lung biopsy specimens for light and electron microscopy were obtained from the upper lobe of the right lung before CPB, 109 min after the start of CPB (just before reperfusion) and 30 min after weaning (after reperfusion). A portion of the lung biopsy specimen was taken for a water content measurement at the same time intervals. For measuring the left and right atrial leukocyte counts, blood samples were taken before thoracotomy, 5 and 109 min after the start of CPB, and 30 and 120 min after weaning. C3a was measured before thoracotomy, 109 min after the start of CPB, and 30 and 120 min after weaning. Plasma malondialdehyde (MDA) was checked before thoracotomy, 109 min after the start of CPB and 30 min after weaning. On both light and electron microscopic examination, mild to moderate acute lung change was observed after ischaemia-reperfusion. Interstitial oedema, leakage of erythrocytes into the alveolar space and endothelial cell swelling were the main findings. However, few neutrophils were seen. Water content of the lung showed a slight increase after the start of CPB, but there was no statistical significance. Neither significant differences in the transpulmonary gradients of leukocytes nor a significant complement activation, expressed by C3a levels, was observed. The MDA level did not display a significant change related to lung reperfusion despite an increase in MDA after the start of CPB. These findings indicate that I-R injury during CPB may not be from complement-activation leukocyte sequestration, but from another source of oxygen free radicals related to CPB.

Castleman's disease represents an atypical lymphoproliferative disorder, infrequently associated with various immunologic abnormalities or subsequent development of malignancy such as Kaposi sarcoma, malignant lymphoma and plasmacytoma. Its clinicopathologic features depend on various etiologic factors such as Kaposi sarcoma herpesvirus (KSHV), oversecretion of IL-6, adhesion molecule and follicular dendritic cell dysplasia, etc. To investigate the relationship of Castleman's disease (CD) and the above factors, we reviewed 22 cases of CD. Four cases of KSHV positive CD were detected, all multicentric, plasma cell type, and these cases displayed prominent vascular proliferation, characteristic 'Kaposi-like lesion'. IL-6 and CD54 positive mononuclear cells were scattered in interfollicular areas of KSHV positive cases. Follicular dendritic cell hyperplasia, vascular proliferation, expression of IL-6 and CD54 did not show any significant difference between solitary vs multicentric type, and plasma cell type vs hyaline vascular type. Our study suggests that KSHV positive CD reveals unique pathologic features, and the probable relationship of KSHV and IL-6 and CD54 is discussed.

BackgroundThe morphological definition of atrial chambers, and the determination of atrial laterality, are based on analysis of the structure of the atrial appendages. The systemic and pulmonary venous connections to the heart, nonetheless, are important in the management of patients having isomeric appendages. In this study, therefore, we analysed the morphology of the postero-superior walls of the atrial chambers so as to provide evidence concerning the morphogenetic background of those hearts, and to improve operative management.MethodsWe reviewed 15 autopsied specimens with isomeric right appendages, and 10 with isomeric left appendages, paying particular attention to the morphology of the systemic and pulmonary venous connections. The postero-superior walls of the atrial chambers can be made up of the atrial body, the systemic venous components, or the pulmonary venous component. We analysed the contributions made by each of these components.ResultsThe postero-superior walls of the atrial chambers were markedly variable, but could be grouped into five patterns. Bilaterally well-developed systemic venous components and absence of the pulmonary venous component within the hypoplastic atrial body were present in 9 hearts with extracardiac pulmonary venous connections in the setting of right isomerism. Bilaterally well-developed systemic venous components, and a hypoplastic pulmonary venous component within the hypoplastic atrial body, were present in 5 hearts with intracardiac pulmonary venous connections in right isomerism. Bilaterally well-developed systemic venous components, and a hypoplastic pulmonary venous component within the sizable atrial body, were present in 1 heart with an intracardiac pulmonary venous connection in right isomerism. A well-developed pulmonary venous component within the atrial body, and hypoplasia of one systemic venous component, were present in 7 hearts with left isomerism. A well-developed pulmonary venous component within the atrial body, and hypoplasia of bilateral systemic venous components, were present in 3 hearts with left isomerism.ConclusionsThe postero-superior walls of the atrial chambers in hearts with isomeric atrial appendages can be analysed on the basis of a compound structure made of bilateral systemic venous components, a central pulmonary venous component, and the body of the atrium. Hearts with isomeric right appendages have absence or hypoplasia of the pulmonary venous component, while hearts with isomeric left appendages have hypoplastic systemic venous components.

In this study of the inhibitory effects of angiopeptin and aspirin on the development of accelerated graft atherosclerosis (AGAS), 22 B10.BR mice received intra-abdominal heterotopic heart transplants from B10.A mice, without immunosuppression. Group 1 (n = 5) received no pharmacological intervention, Group 2 (n = 6) was treated with angiopeptin, Group 3 (n = 5) with aspirin, and Group 4 (n = 6) with both. There was no significant difference in the incidence of AGAS among these groups. The magnitude of intimal lesion development showed less narrowing of large vessels (> 100 microns in diameter) in groups 2 and 4--i.e. the groups received angiopeptin (Group 1 = 46.9 +/- 9.3%, Group 2 = 28.5 +/- 9.2%, Group 3 = 44.1 +/- 10.9%, Group 4 = 24.2 +/- 5.9%; p < 0.01). Comparison of the fraction of tropomyosin-positive staining cells in the intima revealed a lesser degree of staining in Group 2 (p < 0.01). No intervention was effective in preventing smooth muscle cell proliferation in the media or inflammatory cell infiltration in the adventitia. In conclusion, our data suggest that angiopeptin is effective in the direct inhibition of intimal smooth muscle cell proliferation in relatively large vessels, whereas aspirin exhibits no inhibitory role in the progression of AGAS. Angiopeptin appears to be a potential therapeutic agent for inhibiting the progression of postoperative AGAS in clinical heart transplantation.

SummaryAnatomic data are presented of a female abortus with the unusual combination of Ebstein's malformation and atrioventricular septal defect with right isomerism of the atrial appendages, left-hand ventricular topology and discordant ventriculoarterial connection. The common atrioventricular orifice was guarded by an effectively common valve, the right half being guarded by a well-formed three-leaflet valve, but the posterior and left lateral wall of the orifice being deficient of valvar leaflet tissue. The right ventricular inlet was a blind chamber, an imperforate dimple being seen which was surrounded by valvar remnants. The apical trabecular and outlet components of the right ventricle communicated with the left ventricle through an outlet ventricular septal defect in front of the anterosuperior leaflet of the atrioventricular valve, giving the potential clinically for the lesion to be misdiagnosed as double inlet left ventricle.

BACKGROUND--The location of the sinus node is known to be at best abnormal, or at worst unknown, in patients with isomerism of the morphologically left atrial appendage. In contrast, the sinus node is known to be an excellent histological marker of the morphologically right appendage, being duplicated in those with right isomerism. The aim of the study was to investigate this condition further in fetal human and mouse hearts. METHODS--Serial histological sections of the area anticipated to contain the sinus node were studied in hearts with isomerism of the atrial appendages taken from 14 human fetuses and 13 iv/iv mice, using 12 mouse hearts with normally arranged or mirror imaged atrial chambers for controls. RESULTS--All hearts with isomerism of the right appendages (two human and four mouse) had bilateral sinus nodes. The cases with isomerism of the left appendages (12 human and nine mouse) showed absence of a recognisable sinus node except in four cases (19%) in which a small remnant of the node was found. In three of these cases, it was related postero-inferiorly to the superior cavoatrial junction. CONCLUSIONS--The concept of isomerism of the atrial appendages is endorsed by findings on the morphology of the sinus node, this being the most reliable histological criterion for existence of a morphologically right atrium. A small proportion of hearts with left isomerism had a structure resembling the sinus node, but it was hypoplastic and displaced postero-inferiorly, distant from its expected position had the hearts possessed an incompletely formed morphologically right appendage.

Thirty-six pairs of conjoined twins are reviewed from the joint experience of the authors. The external forms of conjunctions were 18 thoracopagus (joined at chest), eight cephalothoracopagus (joined at head and chest), eight dicephalus (single trunk and two heads), one craniopagus (joined at head), and one omphalopagus (joined at abdomen). There was one case with a single conventional heart in association with isomerism of the left lungs and absence of the heart in the left-side twin. Six cases had two conventional hearts. All of them had associated lesions, which were more severe in three cases (50%) with abnormal laterality. All of the cephalothoracopagus (eight cases) had two shared hearts. Cardiac lesions were commonly seen in the posterior heart, but the arrangement of atrial appendages were normal in every heart. Twenty-one cases of either dicephalus or thoracopagus had a compound heart. Three cases (14%) had fusion only at the level of venous sinus; three others (14%) were fused at the atrial level only, but 15 cases (71%) had fusion at both atrial and ventricular levels. Abnormal laterality was an associated lesion in ten cases (48%) with a compound heart. The fusion at the atrial level always occurred between right atriums, but ventricular fusion was more commonly between two left ventricles. Four atrial or ventricular chambers, if fused, were arranged in a cruciate arrangement. Mode of conjunction was as important, in the formation of the cardiovascular system, as was the degree of fusion. Abnormal laterality, which is commonly associated in lateral or mixed lateral/facing conjunction, was the most important factor affecting the general morphology of the cardiovascular system.

BACKGROUND In the management of hearts with deranged laterality, it is essential that the left and right atrial chambers are correctly identified. There are two major approaches, which are based on venous connections or on the morphology of the atrial appendages, and there is no consensus as to which is the most useful. We used the iv/iv mouse mutant, which is known to be pertinent to this problem, to evaluate the relations of cardiac defects with atrial, venous, and other visceral morphologies. METHODS AND RESULTS The morphology of the heart and other organs was examined in 275 iv/iv mice using criteria based on abnormal laterality in humans. The arrangement of the atrial appendages was determined by morphological examination of the junction between the appendage and the venous component of the atrium. On this basis, 45.1% of cases were shown to have usual atrial arrangement, 50.2% had mirror imagery, 1.5% had right isomerism, and 3.3% had left isomerism. Every case of atrial isomerism had a cardiac lesion; the morphological types were similar to those seen in human cases. Of cases with either usual or mirror-image arrangement of the appendages, 33.2% had abnormal spleens, but only 3.1% had cardiac defects. Similarly, venous abnormalities were much more common (30.1%) than cardiac defects. CONCLUSIONS Study results endorse the importance of the morphology of atrial appendages in predicting cardiac abnormalities and point to the marked inconsistency of the arrangement of other organs, including the spleen and the connections of the systemic veins.

Background Acute kidney injury frequently accompanies sepsis. Endotoxin is known to reduce tissue levels of cAMP and low levels of cAMP have been associated with renal injury. We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP and that amrinone an inhibitor of PDE3 would prevent the renal injury. Methods Animals were divided into three groups (n = 7/group): 1) Control (0.9% NaCl infusion without LPS); 2) LPS (0.9% NaCl infusion with LPS); 3) Amrinone+LPS (Amrinone infusion with LPS). Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and the rats followed for 3 hours. We explored the expression of PDE3 isoenzymes and the concentrations of cAMP in the tissue. Results The PDE3B gene but not PDE3A was upregulated in the kidney of LPS group. Immunohistochemistry also showed that PDE3B was expressed in the distal tubule in the controls and LPS caused PDE3B expression in the proximal as well. However, PDE3A was not expressed in the kidney either in the control or LPS treated groups. Tissue level of cAMP was decreased after LPS and was associated with an increase in blood urea nitrogen, creatinine, ultrastructural proximal tubular changes, and expression of inducible nitric oxide synthase (iNOS) in the endotoxemic kidney. In septic animals the phosphodiesterase 3 inhibitor, amrinone, preserved the tissue cAMP level, renal structural changes, and attenuated the increased blood urea nitrogen, creatinine, and iNOS expression in the kidney. Conclusion These findings suggest a significant role for PDE3B as an important mediator of LPS-induced acute kidney injury.

A superior and anterior location of the tricuspid valve in the setting of malalignment between the atrial and ventricular septal structures was the characteristic unifying morphologic feature of seven autopsied hearts with twisted atrioventricular connections. The peculiar angiocardiographic appearances of this lesion could be readily explained by the findings of unusual recesses in the right atrium, in the right ventricle, and in the left ventricle. The recess in the morphologically left ventricle was seen in each case at the right posterior part (or, in the hearts with left-handed ventricles, at the left part) of the chamber. Displacement of the right-sided atrioventricular valve far from the inferior caval vein (vena cava) had produced the recess in the morphologically right atrium; this feature was most prominent in the heart in which the atrioventricular connections were discordant. The recess within the right ventricular outflow tract was seen in four hearts, in all of which the inlet and apical trabecular components of the right ventricle were hypoplastic.

흡연은 만성 폐쇄성 폐질환의 가장 흔하고 중요한 원인이며 발생기전으로 단백분해효소 및 그 억제제의 불균형에 의한 폐조직 파괴가 중요한 역할을 한다고 알려져 있다. 생체내의 여러 단백분해효소 중 matrix metalloproteases (MMPs) 의 역할에 대한 연구가 최근 활발한데, 이들의 다수는 젤라틴 분해능을 보인다. 연구자들은 흡연에 의한 MMPs의 발현 및 폐기종 발생과의 관련성을 규명하기 위한 첫 단계로 기니픽에서 흡연에 의한 젤라틴 분해 단백분해효소의 발현 양상을 알아보고자 하였다. 방 법 : 500gm 가량의 건강한 기니핀 15마리를 대조군 5마리, 6주 흡연군 5마리, 12주 흡연군 5마리 씩 배정한 후, 하루에 5시간 씩, 담배 20개피를 간접 흡연시키는 과정을 일주일에 5회 반복하였다. 흡연력의 정도에 따른 폐조직 내 세포 침윤의 증가를 알아보기 위해, 폐조직을 H&E 염색한 후 400배 확대 시야에서 보이는 폐포벽의 세포 수를 계산하여 일반선형모델을 이용한 통계 분석법으로 처리하였다. 흡연에 의한 젤라틴 분해 단백분해효소의 발현 양상을 알아보기 위해 기관지폐포세척술을 시행하여 폐포내 세포를 얻은 다음 이를 배양접시에 $1{\times}10^6$ 개 씩 분주하였는데, 한 배양접시에는 아무 처치도 하지 않았고 다른 한쪽은 0.1mM의 EDTA를 첨가하였다. 48시간의 배 양 후 얻은 상층액으로 'gelatin zymography'를 시행하여 젤라틴 분해 단백분해효소의 발현 및 EDTA에 의한 억제 여부를 관찰하였다. 결 과 : 대조군의 혈중 평균 COHb 농도는 4.1g/dl인 반면, 흡연 노출군의 혈중 평균 COHb 농도는 5시간 노출 직후에는 24g/dl, 노출 후 30분에는 18g/dl, 노출 후 1 시간 후에는 15g/dl 로 측정되어 충분한 흡연노출이 이루어졌다. 400배 시야에서 보이는 폐포벽의 세포 수는 대조군은 $121.4{\pm}7.2$ , 6주 흡연군은 $158.0{\pm}20.2$ . 12주 흡연군은 $196.8{\pm}32.8$ 로 측정되어 선형회귀관계가 관찰되었다(p=0.001, $r^2=0.675$ ). 또한 침윤된 세포의 대부분은 염증 세포였다. 한편, 대조군에서는 젤라틴 분해 단백분해효소가 발현되지 않은 반면에, 6주 흡연군 및 12주 흡연군에서는 젤라틴분해 단백분해효소가 여러 개 관찰되었다. 또한 이 중의 일부는 EDTA에 의해 효소 활성도가 억제되었다. 결 론 : 흡연에 의해 기니픽의 폐조직에서 여러 젤라틴 분해 단백분해효소 발현이 증가하며 이 중의 일부는 MMPs의 억제제인 EDTA 에 의해 억제된다. 이는 흡연에 의해 MMPs의 발현이 증가할 가능성을 시사한다고 하겠다. 【Background : Chronic obstructive pulmonary disease(COPD) is one of the major contributors to morbidity and mortality among the adult population. Cigarette smoking(CS) is undoubtedly the single most important factor in the pathogenesis of COPD. However, its mechanism is unclear. The current hypothesis regarding the pathogenesis of COPD postulates that an imbalance between proteases and antiproteases leads to the destructive changes in the lung parenchyma. This study had two aims. First, to evaluate the effect of CS exposure on histologic changes of the lung parenchyme, and second, to evaluate the effect of CS exposure on the expression of the gelatinolytic enzymes in BAL fluid cells in guinea pigs. Methods : Two groups of five guinea pigs were exposed to the whole smoke of 20 commercial cigarettes per day, 5 hours/day, 5 days/week, for 6weeks, and 12 weeks, respectively, using a smoking apparatus. Five age-matched guinea pigs exposed to room air were used as controls. Five or more sections were microscopically extamined( ${\times}400$ ) and the number of cellular infiltration of the alveolar wall was measured in order to evaluate the effect of CS exposure on the histologic changes of lung parenchyme. The statistical significance was analyzed by a linear regression method. To evaluate the expression of the gelatinolytic enzymes in intraalveolar cells, BAL fluid was obtained and the intraalveolar cells were separated by centrifugation (500 g for 10 min at $4^{\circ}C$ ). Two sets of culture plates were loaded with $1{\times}10^6$ intraalveolar cells. One plate, contained O.1mM EDTA, a inhibitor of matrix metalloproteases(MMPs), and the other plate had no EDTA. Both plates were incubated for 48 hours at $37^{\circ}C$ . After incubation, gelatinolytic protease expression in the supernatants was analyzed by gelatin zymography. Results : At the end of CS exposure, the level of blood carboxy Hb had increased significantly(4.1g/dl in control group, 24g/dl immediately after CS exposure, 18g/dl 30 min after CS exposure, 15g/dl 1 hour after CS exposure). Alveolar inflammatory cells were identified in the CS exposed guinea pigs. The number of alveolar cellular cells observed in a microscopic field ( $400{\times}$ ) was $121.4{\pm}7.2$ , $158.0{\pm}20.2$ , $196.8{\pm}32.8$ , in the control, the 6 weeks, and the 12 weeks group, respectively. The increased extent of inflammatory cellular infiltration of the lung parenchema showed a statistically significant linear relationship with the duration of CS exposure(p=0.001, $r^2=0.675$ ). Several types of gelatinolytic enzymes in the intraalveolar cells of CS exposed guinea pigs were expressed, of which some were inhibited by EDT A. However, the gelatinolytic enzymes were not expressed in the control groups. Conclusion : CS exposure increases inflammatory cellular infiltration of the alveolar wall and the expression of gelatinolytic proteases in guinea pigs. EDTA inhibits some of the gelatinolytic proteases. These findings suggest a possibility that CS exposure may increase MMP expression in the lungs of guinea pigs.】

A 72 year old man with simultaneously occurring squamous cell and neuroendocrine carcinomas in association with cryptogenic fibrosing alveolitis is reported. The tumours were separate and both were in the fibrotic area of the right lower lobe.

To establish the early morphogenetic mechanism in retinoid induced cardiac lesions, we investigated the morphology of the heart in cultured rat embryos treated with retinoic acid (RA) at 9.0 and 9.5 days post coitum (d.p.c). Wistar rat embryos were treated with RA (2 x 10(-7) M) for 6 hours from the embryonic day equivalent of 9.0 or 9.5 d.p.c. After further culture in an RA free medium for 2.5 days, embryos were fixed and examined with a stereomicroscope and a scanning electron microscope. Sixty three embryos were treated at 9.0 d.p.c., 14 embryos were treated at 9.5 d.p.c. and 30 embryos were used as control. Abnormal ventricular looping was seen in 31 embryos (49.2%) from the group treated at 9.0 d.p.c., and isomerism of right appendages occurred in 15 (23.8%). Embryos treated with RA at 9.5 d.p.c. showed a low incidence of abnormal ventricular looping (14.3%). We could summarize those abnormal looping as three variants of each looping. The mildest form was hypoplasia of the right ventricle observed in 20 cases. Both the right and left ventricles in the second variant were shifted far to the left or right (10 cases). The third variant was a heart with generalized hypoplasia of both ventricles (3 cases). The incidence of branchial arch anomalies was higher at 9.5 d.p.c. than at 9.0 d.p.c. (71.4% and 30.2%, respectively). Abnormalities in the ventricular looping and the atrial laterality at 9.0 d.p.c. suggest that RA induces derangement in the development of laterality, while at 9.5 d.p.c., the abnormality of the migration of neural crest cells is the principal mechanism.

We studied the biological effect of a magnetic field on murine brain and kidney. Magnetic field we used was generated by Magno-DR apparatus (Hanil Co., Korea) which produced a high density unipolar square pulsating magnetic field, about 0.3 approximately 0.5 Tesla at 7 Hertz. Animals were placed in the chamber of the machine for various times from 4 hours to 24 hours. Histological sections of brain and kidney were made after perfusion fixation with paraformaldehyde. The light microscopic examination showed eosinophilic change of cytoplasm and positive immunohistochemical reaction to amyloid precursor protein in the neurons of the cerebral cortex. However, the thalamus and brain stem were less affected. The changes in the brain was seen in the mouse exposed more than 12 hours. The renal tubular epithelium showed degenerated tubules scattered in cortical area but little change was noted in glomeruli in the cortex and collecting tubules in the medulla. Immunohistochemistry of the kidney showed weakly positive reaction for the amyloid precursor protein in the distal tubular epithelium after 4 hours of exposure. These data suggest that strong pulsating magnetic fields could induce deleterious effect on the murine brain tissue and renal cortical tubules.