Third heart sound in hospitalised patients with acute heart failure: insights from the ATTEND study.

BACKGROUND: Several previous studies have suggested that detection of a third heart sound (S3) in patients with chronic congestive heart failure is associated with adverse long-term outcomes. However, the short-term prognostic value of identifying an S3 on admission in patients with acute heart failure (AHF) is not well established. We therefore analysed the in-hospital prognostic value of detecting an S3 on admission in hospitalised patients with AHF. METHODS: The Acute Decompensated Heart Failure Syndromes (ATTEND) study investigators enrolled 4107 patients hospitalised with AHF. Investigators evaluated the presence or absence of an S3 during routine physical examination. RESULTS: On admission to hospital, 1673 patients (41%) had an S3. Patients with an S3 had a higher heart rate, higher serum level of B-type natriuretic peptide and higher creatinine levels than patients without an S3. However, there were no significant differences of systolic blood pressure, serum sodium, haemoglobin, C-reactive protein and total bilirubin between the two groups. Multivariate analysis adjusted for various markers of disease severity revealed that only the presence of an S3 was independently associated with an increase of in-hospital all cause death [adjusted odds ratio (OR), 1.69; 95% confidence interval (CI), 1.19-2.41; p = 0.003] and cardiac death (adjusted OR, 1.66; 95% CI, 1.08-2.54; p = 0.020) among the congestive physical findings related to heart failure (S3, rales, jugular venous distension and peripheral oedema). CONCLUSIONS: Detecting an S3 on admission was independently associated with adverse in-hospital outcomes in patients with AHF. Our findings suggest that careful bedside assessment is clinically meaningful.

Gingival metastasis of ovarian carcinoma: report of a case and review of the literature.

Diagnosing gingival metastases is difficult because clinically they can mimic benign oral lesions. The authors report an unusual case of metastatic ovarian carcinoma in the gingiva of a 46-year-old woman 5 years after ovariectomy. The tumor presented as an exophytic growth at the molar region of the mandible. Histological examination showed invasive proliferation of atypical glandular structures composed of mucin-producing cells laying in a fibrous stroma. Tumor cells were immunopositive for carcinoembryonic antigen, MUC1 mucin, and lysozyme, while stromal fibroblasts were immunopositive for vimentin and estrogen receptor. The diagnosis of metastatic ovarian mucinous cystadenocarcinoma was made. A review of the English literature revealed this to be the first report of gingival metastasis of an ovarian carcinoma.

Synthetic study of macquarimicins: highly stereoselective construction of the AB-ring system.

The highly stereoselective synthesis of the AB-ring system of macquarimicins, a novel class of microbial metabolites with inhibitory activity for neutral sphingomyelinase, has been achieved. The present synthesis features the highly stereocontrolled construction of the cis-tetrahydroindan structure via the intramolecular Diels-Alder reaction of an (E,Z,E)-1,6,8-nonatriene derived from D-glyceraldehyde acetonide. Reaction: see text.

Localization of cytosolic NADP-dependent isocitrate dehydrogenase in the peroxisomes of rat liver cells: biochemical and immunocytochemical studies.

Two types of NADP-dependent isocitrate dehydrogenases (ICDs) have been reported: mitochondrial (ICD1) and cytosolic (ICD2). The C-terminal amino acid sequence of ICD2 has a tripeptide peroxisome targeting signal 1 sequence (PTS1). After differential centrifugation of the postnuclear fraction of rat liver homogenate, approximately 75% of ICD activity was found in the cytosolic fraction. To elucidate the true localization of ICD2 in rat hepatocytes, we analyzed the distribution of ICD activity and immunoreactivity in fractions isolated by Nycodenz gradient centrifugation and immunocytochemical localization of ICD2 antigenic sites in the cells. On Nycodenz gradient centrifugation of the light mitochondrial fraction, ICD2 activity was distributed in the fractions in which activity of catalase, a peroxisomal marker, was also detected, but a low level of activity was also detected in the fractions containing activity for succinate cytochrome C reductase (a mitochondrial marker) and acid phosphatase (a lysosomal marker). We have purified ICD2 from rat liver homogenate and raised a specific antibody to the enzyme. On SDS-PAGE, a single band with a molecular mass of 47 kD was observed, and on immunoblotting analysis of rat liver homogenate a single signal was detected. Double staining of catalase and ICD2 in rat liver revealed co-localization of both enzymes in the same cytoplasmic granules. Immunoelectron microscopy revealed gold particles with antigenic sites of ICD2 present mainly in peroxisomes. The results clearly indicated that ICD2 is a peroxisomal enzyme in rat hepatocytes. ICD2 has been regarded as a cytosolic enzyme, probably because the enzyme easily leaks out of peroxisomes during homogenization. (J Histochem Cytochem 49:1123-1131, 2001)

[The effect of lymphocytapheresis on multiple sclerosis].

We studied the effect of lymphocytapheresis (LCP) on the expanded disability status scale (EDSS) clinical score, lymphocyte subsets and Interleukin-2 (IL-2) production by peripheral blood mononuclear cell (PBM) in 5 patients with multiple sclerosis (MS). The EDSS clinical score significantly decreased after LCPs (p < 0.05). PBM IL-2 production and CD 4/8 ratio significantly decreased (p < 0.05, p < 0.05), and the number of neutrocytes and CD 11 b+CD 8+ (%) significantly increased immediately after LCP (p < 0.05, p < 0.05). Down-regulation of PBM IL-2 production and CD 4/8 ratio and up-regulation of CD 11 b+CD 8+ may account for therapeutic effect of LCP on MS. However, similar changes were observed in patients with CIDP and MG during immunoadsorbent therapy (IAT). It is possible that down-regulation of PBM IL-2 production and CD 4/8 ratio and up regulation of CD 11 b+CD 8+ and the number of neutrocytes may commonly result from apheresis therapy using extra-corporeal circulation.

Intracellular transport of basement membrane-type heparan sulphate proteoglycan in adenoid cystic carcinoma cells of salivary gland origin: an immunoelectron microscopic study.

ACC3, a human adenoid cystic carcinoma cell system of salivary gland origin, is able to synthesize and secrete a large amount of basement membrane molecules in vitro. To define the ultrastructural secreting pathway of these molecules, we immunolocalized heparan sulphate proteoglycan (HSPG) in ACC3 for 7 days of culture. In the early stage of culture, the main compartments immunolabelled were rough endoplasmic reticulum (rER) and small secretory vesicles. From days 3 to 4 after plating, it was noticed that HSPG was localized in partially dilated spaces of the perinuclear, rER and Golgi cisternae and in lysosomes or those fused with multivesicular bodies and endosomes. On and after day 5, almost every Golgi apparatus showed marked dilatation of the cisternae and HSPG was immunolocalized in these dilated spaces. In the later stage of culture, autophagic vacuoles or secondary lysosomes, which were simultaneously labelled for HSPG and cathepsin D, were accumulated in the cytoplasm. HSPG deposition in the intercellular space was clearly demonstrated from day 1 and increased during the culture. The results indicate that ACC3 cells have an enhanced turnover cycle for HSPG: not only its biosynthesis but also degradation of both endogenous or exogenous HSPG. Such intracellular events may be reflected in the characteristic histology and biological behaviour of adenoid cystic carcinomas.

Spindle cell carcinoma of the gingiva: report of an autopsy case.

An autopsied case of an 80-year-old man with spindle cell carcinoma of the gingiva is reported. The tumor was polypoid and mostly composed of a sarcomatous proliferation of spindle cells with a small focus of squamous cell carcinoma at the stalk portion. The carcinoma metastasized to a cervical lymph node, lungs and pleura with extension to the diaphragm. In the metastatic lymph node, the squamous cell component was more prominent than the spindle cell one, while only anaplastic pleomorphic carcinoma cells were found in the lungs. The spindle or anaplastic cells were immunohistochemically positive for vimentin and carcinoembryonic antigen (CEA) but not for other epithelial antigens. We have concluded that the sarcomatoid component arose from the oral squamous cell carcinoma by a metaplastic process. This is the first case report of an oral spindle cell carcinoma examined by autopsy.

Pseudocyst formation by adenoid cystic carcinoma cells in collagen gel culture and in SCID mice.

In order to reconstruct the characteristic three-dimensional architecture of adenoid cystic carcinoma, we cultured ACC2 cells, a cell system established from a human adenoid cystic carcinoma of the palate, in collagen gel matrix and transplanted them in SCID mice. In the collagen gel culture, the cells formed spherical colonies measuring 75.6 +/- 14.6 microns in diameter by 6 days after seeding. The tumor cell nests contained vacuolar structures that were immunopositive for heparan sulfate proteoglycan, type III collagen, type IV collagen, and fibronectin. The rim of the nests was argyrophilic and immunopositive for type I collagen, type IV collagen, laminin, and fibronectin. Transplants of ACC2 cells in SCID mice grew to form tumor masses in which pseudocysts were formed. The results indicate that our collagen gel culture system provides physiological conditions for ACC2 cells to secrete particular extracellular matrix molecules and form pseudocystic spaces.

Weighted distributed feedback structure for all-optical bistable devices.

We proposed to use a distributed feedback structure with a weighted coupling coefficient (W-DPB) in an all-optical bistable device in order to improve on-state transmittance and to reduce threshold intensity. Through numerical calculations, characteristics of the W-DPB structure were discussed compared with those of a conventional DPB structure. The W-DPB optical bistable device exhibits high on-state transmittance and low-threshold input intensity. Fabrication of the W-DPB structure with a periodicity of 169.8 nm is demonstrated on a CdS(x)Se(1-x)-doped glass substrate by means of holographic exposure with a double-coated photoresist and reactive ion etching in CHP(3).

Biosynthesis of basement membrane molecules by salivary adenoid cystic carcinoma cells: an immunofluorescence and confocal microscopic study.

The biosynthesis of basement membrane molecules and fibronectin was studied in vitro in the two different human cell systems (ACC2 and ACC3) established from adenoid cystic carcinomas (ACC) of the salivary gland using immunofluorescence and confocal microscopy. When cells were attached and spread on dishes, fine granular immunofluorescence for type IV collagen, laminin, heparan sulphate proteoglycan, entactin, and fibronectin first appeared diffusely in the cytoplasm, and then changed in aggregation of coarse granules in the perinuclear area. With formation of colonies, these signals were present in the extracellular space, initially in the basal aspect of attached cells and consequently in the lateral intercellular space. After the cells formed a confluent monolayer, extracellular signals started to decrease in inverse proportion to the reappearance of intracellular ones. The results indicate that the parenchymal cells of ACC synthesize these five extracellular matrix molecules, secrete them into the extracellular milieu and remodel the extracellular deposits. It is suggested that the characteristic stromal architecture of ACC, represented by stromal pseudocysts, results from their own secretion of the basement membrane molecules and fibronectin.