Late-gestation prediction of outcome in tricuspid valve dysplasia and Ebstein's anomaly using fetal tricuspid regurgitation waveform analysis.

OBJECTIVE: To investigate the criteria, based on fetal TR waveforms in late gestation, to predict biventricular circulation (BV) after birth in cases of tricuspid valve dysplasia (TVD) or Ebstein's anomaly diagnosed during the fetal period. METHODS: We included 35 consecutive cases diagnosed with TVD or Ebstein's anomaly during the fetal period between January 2008 and December 2021 at Kanagawa Children's Medical Center, Kanagawa, Japan. The maximum velocity and change in pressure over time of tricuspid regurgitation (TR) jet (dP/dt), estimated using TR waveforms obtained during the late-gestation period (gestational age ≥ 28 weeks), were collected from patient records. dP/dt was calculated by dividing the change in estimated right ventricular pressure obtained using Bernoulli's principle by the time taken for the TR maximum velocity to change from one-third to two-thirds of its peak value. The outcome was divided into four categories: BV, single ventricular circulation, neonatal death and fetal death. Patients with BV were included in the BV group, while patients with single ventricular circulation, neonatal death or fetal death were included in the non-BV (NBV) group. RESULTS: Overall, 19 and 16 patients were included in the BV and NBV groups, respectively. The median TR maximum velocity was 3.3 (range, 2.4-3.6) m/s in the BV group and 1.9 (range, 1.0-3.3) m/s in the NBV group. There were no cases of postnatal BV in fetuses with TR maximum velocity < 2.4 m/s; cases with TR maximum velocity of 2.4-3.3 m/s were observed in both BV and NBV groups. Receiver-operating-characteristics-curve analysis was performed on the 11 patients in the BV group and five patients in the NBV group with a TR maximum velocity of 2.4-3.3 m/s. dP/dt ≥ 350 mmHg/s and TR maximum velocity ≥ 2.9 m/s were identified as criteria for predicting the outcome in such cases. The performance of dP/dt ≥ 350 mmHg/s in predicting BV after birth in fetuses with TVD or Ebstein's anomaly was higher compared to that of TR maximum velocity ≥ 2.9 m/s (sensitivity, 90.9% vs 72.3% and specificity, 80.0% vs 80.0%, respectively). CONCLUSIONS: In fetuses with TVD or Ebstein's anomaly, the postnatal outcome may be BV or NBV when the TR maximum velocity is 2.4-3.3 m/s. In such cases, by combining the TR maximum velocity with dP/dt ≥ 350 mmHg/s, BV after birth may be predicted with greater accuracy. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration.

INTRODUCTION: Mesenchymal stromal/stem cells (MSCs) are multipotent, self-renewing cells that are extensively used in tissue engineering. Dedifferentiated fat (DFAT) cells are derived from adipose tissues and are similar to MSCs. Three-dimensional (3D) spheroid cultures comprising MSCs mimic the biological microenvironment more accurately than two-dimensional cultures; however, it remains unclear whether DFAT cells in 3D spheroids possess high osteogenerative ability. Furthermore, it is unclear whether DFAT cells from 3D spheroids transplanted into calvarial bone defects are as effective as those from two-dimensional (2D) monolayers in promoting bone regeneration. METHODS: We compared the in vitro osteogenic potential of rat DFAT cells cultured under osteogenic conditions in 3D spheroids with that in 2D monolayers. Furthermore, to elucidate the ability of 3D spheroid DFAT cells to promote bone healing, we examined the in vivo osteogenic potential of transplanting DFAT cells from 3D spheroids or 2D monolayers into a rat calvarial defect model. RESULTS: Osteoblast differentiation stimulated by bone morphogenetic protein-2 (BMP-2) or osteogenesis-inducing medium upregulated osteogenesis-related molecules in 3D spheroid DFAT cells compared with 2D monolayer DFAT cells. BMP-2 activated phosphorylation in the canonical Smad 1/5 pathways in 3D spheroid DFAT cells but phosphorylated ERK1/2 and Smad2 in 2D monolayer DFAT cells. Regardless of osteogenic stimulation, the transplantation of 3D DFAT spheroid cells into rat calvarial defects promoted new bone formation at a greater extent than that of 2D DFAT cells. CONCLUSIONS: Compared with 2D DFAT cells, 3D DFAT spheroid cells promote osteoblast differentiation and new bone formation via canonical Smad 1/5 signaling pathways. These results indicate that transplantation of DFAT cells from 3D spheroids, but not 2D monolayers, accelerates bone healing.

Bioclimatic zoning and trend analysis applied to broilers / Zoneamento bioclimático e análise de tendência aplicados a frangos de corte

The objective of the present study was to establish the bioclimatic zoning by the temperature and humidity index (THI), considering a historical period and a future scenario, in order to represent the thermal environment for broiler breeding in the State of Minas Gerais. A historical series (1976 - 2014) of THI minimum, average and maximum calculated based on data from 48 conventional meteorological stations was used, belonging to the National Institute of Meteorology of the State of Minas Gerais. The analysis of the temporal series was based on the Mann-Kendall test and linear regression. A geostatistical analysis was also carried out to determine the comfort zoning of broilers as a function of the THI intervals. In this way, the THI spatial mapping methodologies and trend analysis for the prediction of a possible future climate scenario can help in the development of risk maps for monitoring thermal comfort of broilers, being indispensable in the planning of actions for the mitigation of the climatic change impacts on the productive chain of the State of Minas Gerais.(AU)

O objetivo do presente trabalho foi estabelecer o zoneamento bioclimático por meio do índice de temperatura e umidade (ITU), considerando-se um período histórico e um cenário futuro, de forma a representar o ambiente térmico para criação de frangos de corte no estado de Minas Gerais. Foi utilizada uma série histórica (1976 - 2014) de ITU mínimo, médio e máximo, que foram calculados com base em dados oriundos de 48 estações meteorológicas convencionais, pertencentes ao Instituto Nacional de Meteorologia do Estado de Minas Gerais. A análise da série temporal se baseou no teste de Mann-Kendall e na regressão linear. Procedeu-se, também, à análise geoestatística para determinação do zoneamento do conforto de frangos de corte segundo os intervalos de ITU. Dessa forma, as metodologias de mapeamento espacial do ITU e a análise de tendência para predição de um possível cenário climático futuro podem auxiliar no desenvolvimento de mapas de risco para o monitoramento do conforto térmico de frangos de corte, sendo indispensáveis no planejamento de ações para mitigação dos impactos das mudanças climáticas sobre a cadeia produtiva do estado de Minas Gerais.(AU)

Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes.

OBJECTIVE: Previous studies have shown that enolase-1 (ENO1) in the stratum corneum (SC) is more highly expressed in patients with atopic dermatitis (AD) than in healthy individuals, suggesting that it is a novel biomarker for evaluating skin condition in patients with AD. However, the mechanism underlying high ENO1 expression in the SC and its pathological relevance in AD are unclear. In this study, the relationship between ENO1 expression and keratinization of epidermis was investigated, and the role of high ENO1 expression in keratinocytes was characterized. METHODS: ENO1 expression and morphological characteristics were examined in SC from the cheeks of 24 patients with AD. Additionally, the localization of ENO1 in the excised human epidermis was observed. Moreover, to analyse the role of ENO1 in cellular barrier function, tight junction proteins (TJs) and transepithelial electrical resistance (TEER) in keratinocytes with ENO1 overexpression were evaluated. Furthermore, the localization of ENO1 and plasminogen in keratinocytes was evaluated by immunostaining, and the cellular barrier function in keratinocytes was examined after treatment with tranexamic acid (TXA). RESULTS: ENO1 expression was substantially correlated with the rate of nucleated corneocytes in AD. In addition, ENO1 localized in the basal to spinous layers, but was its expression dramatically decreased in healthy human SC. ENO1 overexpression in human epidermal keratinocytes reduced the expression of TJs (claudin-4, E-cadherin, tricellulin, and occludin) and TEER, and treatment with anti-ENO1 IgG reversed these effects. ENO1 colocalized with plasminogen in keratinocytes. Treatment with TXA rescued the ENO1-induced reductions in TJ and TEER expression. CONCLUSION: We found a substantial correlation between ENO1 expression and the rate of nucleated corneocytes in AD and decreased ENO1 expression with nuclear disappearance. These results suggest that high ENO1 expression in the SC of AD is caused by deficient keratinization, which is an AD characteristic. Moreover, ENO1 overexpression in keratinocytes promoted dysfunction of TJ dynamics, leading to reduced integrity of the cellular barrier, and these effects might be mediated by plasmin activity. We propose that ENO1 is a useful indicator of parakeratosis and might have a potential role in cellular TJ barrier function in the epidermis.

MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation.

Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO)7-Cre/Mob1aflox/flox/Mob1b-/-; termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth. Their alveolar epithelial cells showed increased proliferation, impaired YAP1/TAZ-dependent differentiation and decreased surfactant protein production, all features characteristic of human respiratory distress syndrome. Intriguingly, mutant mice that received Dox postnatally (luMob1DKO (P21-41) mice) did not develop spontaneous lung adenocarcinomas, and urethane treatment-induced lung tumour formation was decreased (rather than increased). Lungs of luMob1DKO (P21-41) mice exhibited increased detachment of bronchiolar epithelial cells and decreased numbers of the bronchioalveolar stem cells thought to initiate lung adenocarcinomas. YAP1/TAZ-NKX2.1-dependent expression of collagen XVII, a key hemidesmosome component, was also reduced. Thus, a MOB1-YAP1/TAZ-NKX2.1 axis is essential for normal lung homeostasis and expression of the collagen XVII protein necessary for alveolar stem cell maintenance in the lung niche.

One-year follow-up of transgene expression by integrase-defective lentiviral vectors and their therapeutic potential in spinocerebellar ataxia model mice.

We examined integrase-defective lentiviral vectors (IDLVs) with a mutant (D64V) integrase in terms of their residual integration capability, the levels and duration of transgene expression and their therapeutic potential in comparison to wild-type lentiviral vectors (WTLVs) with a wild-type integrase gene. Compared with WTLVs, the IDLV-mediated proviral integration into host-cell chromosomes was approximately 1/3850 in HeLa cells and approximately 1/111 in mouse cerebellar neurons in vivo. At 2 months, transgene expression by IDLVs in the mouse cerebellum was comparable to that by WTLVs, but then significantly decreased. The mRNA levels at 6 and 12 months after injection in IDLV-infected cerebella were approximately 26% and 5%, respectively, of the mRNA levels in WTLV-injected cerebella. To examine the therapeutic potential, IDLVs or WTLVs expressing a molecule that enhances the ubiquitin-proteasome pathway were injected into the cerebella of spinocerebellar ataxia type 3 model mice (SCA3 mice). IDLV-injected SCA3 mice showed a significantly improved rotarod performance even at 1 year after-injection. Immunohistochemistry at 1 year after injection showed a drastic reduction of mutant aggregates in Purkinje cellsfrom IDLV-injected, as well as WTLV-injected, SCA3 mice. Our results suggest that because of the substantially reduced risk of insertional mutagenesis, IDLVs are safer and potentially effective as gene therapy vectors.

Characterization of urinary peptide biomarkers of acute rejection in renal allografts.

We previously demonstrated that 4.7 kDa and 4.4 kDa peptides are useful in diagnosing acute rejection in renal transplant recipients. The aim of this study was to characterize these polypeptides and assess their potential as biomarkers. The polypeptides were identified as human beta-Defensin-1 (4.7 kDa) and alpha-1-antichymotrypsin (4.4 kDa), by tandem mass spectrometry and ProteinChip immunoassay. The urinary abundance of both polypeptides, assessed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), revealed a reduction in beta-Defensin-1 while alpha-1-antichymotrypsin increased in patients with rejection (p < 0.05) compared with clinically stable transplants. The area under the curve (AUC) for the receiver operator characteristic (ROC) curve for the diagnosis of rejection for the ratio of both peptides combined was 0.912. Longitudinal analysis confirmed a reduction in beta-Defensin-1 with a reciprocal increase in alpha-1-antichymotrypsin as rejection developed. The difference in urinary beta-Defensin-1 levels quantified by radioimmunoassay was 176.8 +/- 122.3 pg/mL in stable patients compared with 83.2 +/- 52.2 pg/mL in patients with acute rejection, with an ROC AUC of 0.749 (p < 0.01). Immunohistochemistry (IHC) confirmed reduced beta-Defensin-1 expression in the renal parenchyma of patients experiencing acute rejection. In conclusion, the ratio of beta-Defensin-1 and alpha-1-antichymotrypsin excretion in the urine is a novel, potentially useful candidate biomarkers of acute rejection.

Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections.

Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.

Flutolanil and carboxin resistance in Coprinus cinereus conferred by a mutation in the cytochrome b560 subunit of succinate dehydrogenase complex (Complex II).

A gene that confers resistance to the systemic fungicide flutolanil was isolated from a mutant strain of the basidiomycete Coprinus cinereus. The flutolanil resistance gene was mapped to a chromosome of approximately 3.2 Mb, and a chromosome-specific cosmid library was constructed. Two cosmid clones that were able to transform a wild-type, flutolanil-sensitive, strain of C. cinereus to resistance were isolated from the library. Analysis of a subclone containing the resistance gene revealed the presence of the sdhC gene, which encodes the cytochrome b560 subunit of the succinate dehydrogenase (SDH) complex (Complex II) in the mitochondrial membrane. Comparison between the sdhC gene of a wild-type strain and that of a mutant strain revealed a single point mutation, which results in the replacement of Asn by Lys at position 80. Measurements of succinate-cytochrome c reductase activity in the transformants with mutant sdhC gene(s) suggest that flutolanil resistance of the fungus is caused by a decrease in the affinity of the SDH complex for flutolanil. This sdhC mutation also conferred cross-resistance against another systemic fungicide, carboxin, an anilide that is structurally related to flutolanil. In other organisms carboxin resistance mutations have been found in the genes sdhB and sdhD, but this is the first demonstration that a mutation in sdhC can also confer resistance. The mutant gene cloned in this work can be utilized as a dominant selectable marker in gene manipulation experiments in C. cinereus.

Immunohistochemical demonstration of salmon olfactory glutathione S-transferase class pi (N24) in the olfactory system of lacustrine sockeye salmon during ontogenesis and cell proliferation.

In mammals, glutathione S-transferase (GST) in the olfactory epithelium is involved in assistance of the olfactory reception by the xenobiotic metabolism. We previously reported the protein and gene expressions of salmon olfactory GST class pi (soGST) in the olfactory receptor cells (ORCs) of the salmonid fish. However, the chronological appearances of soGST in ORCs during ontogeny and cell proliferation are still unknown in this species. In this study, we performed immunohistochemistry of soGST using an antibody specific to soGST in the olfactory system (olfactory placode, olfactory pit, olfactory epithelium, olfactory nerve and olfactory bulb) of lacustrine sockeye salmon ( Oncorhynchus nerka) embryos and 5-bromo-2'-deoxyuridine (BrdU) experimental fish. The projection of olfactory nerve bundles from the olfactory pit to the presumptive olfactory bulb was identified at embryonic day 28 after fertilization. The olfactory cilia were first detected on the apical surface of ORCs at day 43. soGST-immunoreactivity was first detected within the olfactory pit cells at day 55. At 58 day, the number of soGST-immunoreactive cells increased markedly in the olfactory epithelia, and soGST-immunoreactive fibers were observed in the olfactory nerves and olfactory bulbs. By in vivo uptake of BrdU in 1-year-old fish, we observed for the first time at day 7 after labeling that the olfactory epithelia showed ORCs in which both soGST-immunoreactivity and BrdU coexisted. These results indicate that soGST is synthesized in the mature ORCs of lacustrine sockeye salmon after cell formation and differentiation.

[Surgical treatment for ruptured aneurysm of a coronary artery to pulmonary artery fistula; report of a case].

We reported a successful operative case of ruptured coronary artery aneurysm associated with coronary artery to pulmonary artery fistula. The patient was a 74-year-old woman who was admitted for syncope and chest oppression. Echocardiogram and chest CT scan revealed cardiac tamponade. Ruptured coronary aneurysm, 3 cm in diameter, was found at emergent operation. After emergent coronary angiography, which demonstrated an aneurysm arising from the left anterior descending coronary artery and draining into the pulmonary artery, orifice of draining artery to the aneurysm was closed and coronary artery fistula was ligated. She recovered smoothly and post operative angiogram revealed disappearance of the aneurysm.

Adhesion preventive effect of a novel hyaluronic acid gel film in rats.

This study evaluated the efficacy of a novel hyaluronic acid (HA) gel for preventing adhesions in a rat caecal model. The gel was manufactured from an acidic HA solution using a freezing procedure. HA gel films with four different half-lives (50-200 h) in physiological buffered saline at 37 degrees C were prepared, by regulating the freezing time, and tested. The HA gel film was applied as a barrier on the injured caecal surface after standardized treatment with a rotary abrasion apparatus. A control group of 20 animals were abraded in the same way but not treated. Seven days after the initial operation, the incidence and severity of any adhesions were recorded. Application of the HA gel film significantly reduced the incidence and severity of adhesion formation in all treatment groups compared with the control group. This novel HA gel film is effective for reducing post-operative adhesions in this rat model and the resorption rate is optimum for adhesion prevention on the caecal surface.

A simple method for evaluating abnormal lengthening of the QT interval during the face immersion test.

The slope of the relation between the unadjusted QT interval and heart rate during the face immersion test has been reported to be useful as an index for predicting an abnormal lengthening of the QT interval for children with nonfamilial long QT syndrome. Our goals were to determine whether we can replace the slope of the QT/heart rate relation calculated from all data with that calculated from fewer data and to determine whether we can replace the slope with the corrected QT value by heart rate (QTc value) at the minimum heart rate. We studied 19 children with a prolonged QT interval and 54 control children by using statistical analysis. The slope calculated from the selected data points (at least four) was in agreement with the slope calculated from all data, and the relationship between the slope and the QTc value at the minimum heart rate showed a high correlation. It was determined that we can replace the slope calculated from all data with that calculated from at least four data points and replace the slope with the QTc value at the minimum heart rate as an index for predicting an abnormal lengthening of the QT interval.

[Two cases of visceral larva migrans due to Ascaris suum showing a migratory nodular shadow].

The number of cases of visceral larva migrans caused by the pig ascarid, Ascaris suum has recently been increasing. We have encountered two cases of visceral larva migrans due to A. suum with a nodular shadow on the chest radiograph and eosinophilia in the peripheral blood. Patient 1 was a 26-year-old man who had been admitted to our hospital for an elective minor operation. His chest radiology and chest computed tomography revealed a nodule in the left lung field. Peripheral blood eosinophil counts and serum IgE values were elevated. Radiological abnormality disappeared without treatment. Patient 2 was a 57-year-old man who had been admitted to our hospital because of a migratory nodule on chest radiography and eosinophilia in the peripheral blood. The diagnosis of visceral larva migrans caused by A. suum was made because the serum of both patients was positive for an antibody against A. suum. Patient 1 and patient 2 were accustomed to eating the raw flesh of wild boar and deer, and of chicken and turkey, respectively. Treatment with albentazole was effective in these patients.

Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice.

Mice deficient in the Syk tyrosine kinase showed severe petechiae in utero and died shortly after birth. The mechanism of this bleeding, however, remains unknown. Here it is shown that this bleeding is caused by morphologic defects of Syk-deficient endothelial cells during embryogenesis. Immunoblot and reverse transcriptase-polymerase chain reaction Northern blot analysis indicated that Syk is expressed in several endothelial cell lines. Immunocytochemical analysis also confirmed that Syk is expressed in the normal embryonic endothelial cells and is absent in Syk-deficient mice. Furthermore, electron microscopic analysis of Syk-deficient mice revealed an abnormal morphogenesis and a decreased number of endothelial cells. The results indicate a critical role for Syk in endothelial cell function and in maintaining vascular integrity in vivo.

Syk expression and novel function in a wide variety of tissues.

Syk protein-tyrosine kinase has been implicated in a variety of hematopoietic cell responses, in particular immunoreceptor signaling events that mediate diverse cellular responses including proliferation, differentiation, and phagocytosis. On the other hand, Syk exhibits a more widespread expression pattern in nonhematopoietic cells like fibroblasts, epithelial cells, breast tissue, hepatocytes, neuronal cells, and vascular endothelial cells and has been shown to be functionally important on these cell types. Thus, Syk appears to play a general physiological function in a wide variety of cells. In this article, we briefly review the current literature regarding the expression and novel function of Syk in various cells and tissues.

Adhesion via CD43 induces Syk activation and cell proliferation in TF-1 cells.

The effect of adhesion via CD43 (leukosialin, sialophorin) on cell proliferation and phosphorylation signaling were examined in a growth factor-dependent hematopoietic progenitor cell line, TF-1. TF-1 cells promptly resulted in death after withdrawal of growth factors. However, the viable cell number increased when TF-1 cells were cultured on anti-CD43 monoclonal antibody-coated plates. In this case, sustained activation of protein tyrosine kinase Syk and extracellular signal-regulated kinase (Erk) 1/2 were detected. Overexpression of exogenous Syk on TF-1 cells by the adenovirus vector system induced enhancement of the cell proliferation accompanied with enhancement of the Erk activation by a dominant-positive effect. The signal transducer and activator of transcription (STAT) 5 seemed not to be associated with the CD43-mediated cell proliferation. These results indicated that adhesion via CD43 induces the proliferation of TF-1 cells in the absence of growth factors in part by Syk-dependent Erk 1/2 signaling.

Solitary fibroleiomyomatous hamartoma of the lung in a patient without a pre-existing smooth-muscle tumor.

A solitary well-demarcated tumor was found in the left lung of a 53-year-old man. It was located in the posterior region of the lower lobe just adjacent to, but apart from, the pleura. It was resected by video-associated thoracic surgery. Macroscopically, the tumor was a whitish solid nodule without hemorrhage or necrosis, and it was 1.5 cm in diameter. Histologically, the tumor consisted of a proliferation of fibromuscular tissue in interlacing fascicles in which many tubular or cleft-like epithelial inclusions were involved. The epithelial inclusions showed cystic changes with goblet cell metaplasia in part, but no atypical changes. Other mesenchymal components such as cartilaginous, myxomatous or adipose tissues were not seen. The patient had no history of neoplasm, including smooth-muscle tumor. Thus, we diagnosed this tumor as a "true" fibroleiomyomatous hamartoma, as distinct from so-called fibroleiomyomatous hamartoma or benign metastasizing leiomyoma, which are usually found in the lungs of women who have had hysterectomies, as multiple fibromuscular nodules. We report here this rare case and we review and discuss published reports of fibromuscular tumors of the lung.

A critical role for Syk in endothelial cell proliferation and migration.

Syk is a protein-tyrosine kinase that is widely expressed in haematopoietic cells and involved in coupling activated immunoreceptors to downstream signaling. On the other hand, Syk-deficient mice showed severe petechiae in utero and died shortly after birth. Recently we have shown the expression of Syk in endothelial cells and morphological defects of these cells in embryonic Syk-deficient mice. Here we report that both proliferation and migration of human umbilical vein endothelial cells were severely impaired by adenovirus-mediated expression of Syk dominant negative mutants. Furthermore, a close relationship between Syk kinase activity and extracellular signal-regulated kinase activation was suggested. Our results indicate that Syk plays a critical role in endothelial cell functions, including morphogenesis, cell growth, migration, and survival, and contributes to maintaining vascular integrity in vivo.

Structure and function of Syk protein-tyrosine kinase.

Non-receptor type of protein-tyrosine kinase Syk contains 2 Src homology 2 (SH2) domains in tandem and multiple autophosphorylation sites. Syk is activated upon binding of tandem SH2 domains to immunoreceptor tyrosine-based activating motif (ITAM) and plays an essential role in lymphocyte development and activation of immune cells. Syk is critical for tyrosine phosphorylation of multiple proteins which regulate important pathways leading from the receptor, such as Ca(2+) mobilization and mitogen-activated protein kinase (MAPK) cascades. Recent findings reveal that expression of Syk appears to be involved in a wide variety of cellular functions and pathogenesis of malignant cancer. These observations have demonstrated that Syk is a key molecule that controls multiple physiological functions in cells.