BMP-2-producing L cells induce osteogenesis in vivo and in vitro

A high level of expression of the humanbone morphogenetic protein-2 (hBMP-2) gene was found in L cells under control of a cytomegalovirus enhancer and a chicken -actin promoter. The induction of osteogenesis in vitro was examined by treating the stromal cell lines MC3T3-E1, ST2, and OP9 with either conditioned medium (CM) from hBMP-2 L cell transfectants, or with retinoic acid. BMP-2 CM induced alkaline phosphatase (ALP) activity in all three cell lines at different levels, with ALP activity in the OP9 cell line being approximately one-tenth that in the other cell lines. Serum induced ALP activity synergistically with BMP-2 CM. Retinoic acid strongly induced ALP activity only in the ST2 cell line. The different responses of stromal cell lines to BMP-2 CM and retinoic acid characterized stromal and preosteoblastic cells. In an in vivo analysis, BMP-2-producing L cells were injected into the foreleg and thigh muscles of nude mice, resulting in ectopic bone formation.     

Determinants of Alcohol Consumption in Women Before and After Awareness of Conception

Maternal and Child Health Journal - We examined the socio-demographic and behavioral factors associated with alcohol consumption before and after pregnancy awareness in pregnant women. This...     

Impact of dementia on cancer discovery and pain

Background: Dementia is clinically noted to influence both reporting and experience of cancer pains. However, no systemic evaluation of this aspect has been reported. The aim of the present study was to retrospectively evaluate how dementia modified the cancer discovery process, frequency of cancer pain reports and analgesic‐narcotic use at a large psychiatric hospital. Methods: We reviewed all the records of cancer patients with and without dementia treated at the surgical ward of Matsuzawa Hospital from 1993 to 2004. Psychiatric diseases other than dementia, brain metastasis and alcoholism, as well as leukaemia and skin cancer, were excluded. Patients' communicativeness as to pain was ascertained from nursing records. Results: A total of 134 cancer patients with and without dementia (50 demented and 84 non‐demented) were included. Demented patients were accidentally discovered to have cancer (48%) or by an unexpected unfolding of clinical signs (44%), whereas most non‐demented patients (63%) voluntarily sought medical evaluation (P= 0.000). Overall, 76% of non‐demented patients had cancer pains (stages I and II, 64%; stages III and IV, 84%), whereas just 22% of demented patients had cancer pains (stages I and II, 16%; stages III and IV, 26%; P= 0.000). Non‐demented patients showed stage‐dependent requirements for both non‐narcotic analgesics (stages I and II, 64%; stages III and IV, 84%) and narcotics (stages I and II, 0%; stages III and IV, 41%). Demented patients required much less analgesics (stages I and II, 11%; stages III and IV, 13%), with only one stage IV patient requiring narcotics (P= 0.000). Conclusion: Dementia greatly modifies the cancer discovery process, reduces prevalence of cancer pain and analgesic requirement.     

Heterogeneous pulmonary vein myocardial cell repolarization implications for reentry and triggered activity

BACKGROUND: Myocardial cells in the pulmonary veins (PVs) are thought to play a major role in the initiation and maintenance of atrial arrhythmias, including atrial fibrillation. However, systematic single-cell microelectrode recordings from different regions in intact PV-atrial tissues are lacking. OBJECTIVES: The purpose of this study was to determine the transmembrane action potential properties of myocardial cells in different regions of the PV and the left atrium (LA) and assess their arrhythmogenic potential during perfusion with isoproterenol (ISO) and rapid atrial pacing. METHODS: Glass microelectrode recordings of action potentials were made from the left PV and the LA in Langendorff-perfused young (3-4 month) male rats (Fisher344) (n = 9). RESULTS: Action potential duration (APD) of atrial and PV cells had similar duration at a pacing cycle length (CL) of 200 ms. However, shortening of the pacing CL to 100 ms led to heterogeneous repolarization of PV cells. Mid-PV cells had a significantly higher maximum slope of APD restitution than atrial or other PV sites. Intra-PV conduction block developed at rates when LA and proximal PV cells manifested 1:1 capture. Perfusion of ISO and rapid atrial pacing promoted the emergence of early afterdepolarization (EAD) and triggered beats in two out of nine tissues, causing premature atrial activation. No difference in resting potential or AP amplitude could be detected among the PV and LA cells. CONCLUSIONS: PV myocardial cells develop marked heterogeneity in repolarization, and there is a slight ease of developing EAD and triggered activity in response to rapid pacing and ISO infusion.     

Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs

Cardiac nerve sprouting and sympathetic hyperinnervation after myocardial infarction (MI) both contribute to arrhythmogenesis and sudden death. However, the mechanisms responsible for nerve sprouting after MI are unclear. The expression of nerve growth factor (NGF), growth associated protein 43 (GAP43), and other nerve markers were studied at the infarcted site, the noninfarcted left ventricle free wall (LVFW), and the left stellate ganglion (LSG) at several time points (30 minutes to 1 month) after MI. Transcardiac (difference between coronary sinus and aorta) NGF levels were also assayed. Acute MI resulted in the immediate elevation of the transcardiac NGF concentration within 3.5 hours after MI, followed by the upregulation of cardiac NGF and GAP43 expression, which was earlier and more pronounced at the infarcted site than the noninfarcted LVFW. However, cardiac nerve sprouting and sympathetic hyperinnervation were more pronounced in the noninfarcted than the infarcted LVFW site and peaked at 1 week after MI. The NGF and GAP43 protein levels significantly increased in the LSG from 3 days (P<0.01 for all) after MI, without a concomitant increase in mRNA. There was persistent elevation of NGF levels in aorta and coronary sinus within 1 month after MI. We conclude MI results in immediate local NGF release, followed by upregulation of NGF and GAP43 expression at the infarcted site. NGF and GAP43 are transported retrogradely to LSG, which triggers nerve sprouting at the noninfarcted LVFW. A rapid and persistent upregulation of NGF and GAP43 expression at the infarcted site underlies the mechanisms of cardiac nerve sprouting after MI.     

Localization and expression pattern of amelotin,odontogenic ameloblast-associated protein and follicular dendritic cell-secreted protein in the junctional epithelium of inflamed gingiva

The purpose of this study is to elucidate the localization of amelotin (AMTN), odontogenic ameloblast-associated protein (ODAM) and follicular dendritic cell-secreted protein (FDC-SP) at the junctional epithelium (JE) in Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans infected mice and inflamed and non-inflamed human gingiva. We performed immunostaining to determine the localization and expression pattern of AMTN, ODAM and FDC-SP. AMTN, ODAM and FDC-SP in A. actinomycetemcomitans infected mice did not change dramatically compared with non-infected mice. AMTN and FDC-SP expressions were observed stronger in P. gingivalis infected mice at early stage. However, at the following stage, the coronal part of the AMTN expression disappeared from the JE, and FDC-SP expression decreased due to severe inflammation by P. gingivalis. ODAM expressed internal and external basal lamina, and the expression increased not only at early stage but also at the following stage in the inflammatory JE induced by P. gingivalis. In the human gingival tissues, AMTN was detected at the surface of the sulcular epithelium and JE in the non-inflamed and inflamed gingiva, and the localization did not change the process of inflammation. ODAM and FDC-SP were more widely detected at the sulcular epithelium and JE in the non-inflamed gingiva. In the inflamed gingiva, localization of ODAM and FDC-SP was spread into the gingival epithelium, compared to AMTN. These studies demonstrated that the expression pattern of AMTN, ODAM and FDC-SP at the JE were changed during inflammation process and these three proteins might play an important role in the resistance to inflammation.