Serum hepatocyte growth factor levels are increased in patients with congestive heart failure

BACKGROUND: Hepatocyte growth factor (HGF) is a potent endothelial cell-specific mitogen. We investigated the clinical importance of HGF in congestive heart failure (CHF). METHODS AND RESULTS: Thirty-five patients with acute exacerbation of CHF and 7 control subjects were examined. Serum and peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood on days 1, 7, and 14 after admission. PBMCs were cultured at a density of 1 x 10(7) cells/mL for 24 hours. HGF levels in serum and the PBMC culture medium and serum interleukin 6 (IL-6) levels were measured by enzyme-linked immunosorbent assay. Serum HGF levels in patients with CHF were markedly increased at admission compared with those in control subjects and gradually returned to control levels during hospitalization. HGF levels in the PBMC culture medium were also significantly increased in CHF patients compared with control subjects. There was a positive correlation between HGF levels in serum or those in the PBMC culture medium and serum IL-6 levels. HGF levels in serum and the culture medium were not notably different between CHF patients regularly treated with and without angiotensin-converting enzyme inhibitors. CONCLUSIONS: HGF levels in serum are increased in patients with acute exacerbation of CHF.     

Home environment and suspected atopic eczema in Japanese infants: The Osaka Maternal and Child Health Study

Atopic eczema is most commonly diagnosed in children under the age of 5 yr. Environmental factors during pregnancy or in early life may confer risk for childhood atopic eczema. The present prospective study examined the relationship of the perinatal home environment and the risk of suspected atopic eczema among Japanese infants under the age of 1. Study subjects were 865 parent-child pairs. The term 'suspected atopic eczema' was used to define an outcome based on our questionnaire at 2-9 months postpartum. Adjustment was made for maternal age, gestation, family income, maternal and paternal education, maternal and paternal history of asthma, atopic eczema, and allergic rhinitis, time of delivery before the second survey, baby's older siblings, baby's sex, and baby's birth weight. A high mite allergen level from maternal bedclothes and mold in the kitchen during pregnancy were significantly associated with an increased risk of suspected atopic eczema. Frequent vacuuming practices during pregnancy and giving the infant a bath or shower at least once a day were significantly inversely related to the risk of suspected atopic eczema. Maternal smoking, maternal use of a synthetic duvet and pillow, carpet use in the living room and maternal bedroom, indoor domestic pets, no ducted heating appliance, and gas use for cooking during pregnancy and household smoking in the same room as the infant, infant's synthetic duvet, carpet use in the infant's room, or vacuuming the infant's room were not related to the risk of suspected atopic eczema. High house dust mite allergen levels and mold in the kitchen during pregnancy may increase the risk of infantile atopic eczema, whereas frequent vacuuming practices during pregnancy and giving the infant a bath or shower at least once a day may protect against infantile atopic eczema.     

Comparison of the sensitive screening kit with two ELISA sets for detection of anti-Toxocara antibodies

Three serological tests (ELISA NOVUM, ELISA PU and ToxocaraCHEK) were compared using excretory-secretory (ES) antigen of second stage larvae of Toxocara canis on two sets of sera from patients aged 1-15 years, living in town and in the country, suspected of having larval toxocarosis. Of 60 serum samples examined for the presence of anti-Toxocara IgM and IgG antibodies 35 (58.3%) were positive with ELISA NOVUM, 30 (50.0%) with ELISA PU and 37 (61.6%) with ToxocaraCHEK. A significantly higher seropositivity with all the tests was detected in group of patients from the village (test chi2, p < 0.005) when compared with patients from the town. The highest sensitivity (100%) was detected for a rapid qualitative ToxocaraCHEK. Compared with this screening test, both ELISA sets showed higher specificity but a lower sensitivity. Consistent findings (+;-) with ELISA NOVUM and ELISA PU were 88.3%; ELISA NOVUM and ToxocaraCHEK 96.7% and ELISA PU and ToxocaraCHEK 86.7%. This comparison indicates the suitability of ToxocaraCHEK set for screening for its simplicity and rapidity in detecting anti-Toxocara antibodies.     

Pharmacological activities of crocin in saffron

The effect of crocin on improving ethanol-induced impairment of learning behaviors of mice in passive avoidance tasks is reported. Based on these results, it became evident that crocin prevents the inhibitory effect of ethanol on long-term potentiation (LTP) in the dentate gyrus in vivo. We confirmed that crocin inhibits tumor necrosis factor (TNF)-α-induced apoptosis of PC-12 cells. PC-12 cells showed a rapid increase in cellular ceramide levels, followed by an increase in the phosphorylation of c-Jun kinase (JNK), leading to apoptosis by serum/glucose deprivation in the medium. The production of ceramide was dependent on the activation of magnesium-dependent neutral sphingomyelinase (N-SMase), but not on de novo synthesis. The oxidative stress also decreased the cellular levels of glutathione (GSH), which is the potent inhibitor of N-SMase. Crocin treatment resulted in the prevention of N-SMase activation, ceramide production and JNK phosphorylation. Exploration of the crocin’s preventive mechanism in oxidative stress-induced cell death revealed that the activities of GSH reductase and γ-glutamylcysteinyl synthase (γ-GCS) in the γ-glutamyl cycle affected the stable GSH supply that blocks the activation of N-SMase. These results strongly support the importance of the proposed GSH-dependent inhibitory mechanism in oxidative stress-mediated cell death.     

Eastern blotting and use of anti-saikosaponin a monoclonal antibodies for detection of saikosaponins

Immunochemical assays using anti-saikosaponin a monoclonal antibody (MAb) and so-called Eastern blotting have been established for semi-quantitative analysis of the saikosaponins (SS) SSa, SSb₂, SSc, and SSd, which are active constituents of the Bupleuri radix. After crude separation of saikosaponins by TLC, compounds were transferred from the TLC plate to a PVDF membrane where they were oxidized with NaIO₄ and, finally, conjugated with bovine serum albumin (BSA). Clear and specific detection and identification of the immobilized saikosaponin–BSA conjugates were achieved by use of the MAbs. Compared with TLC, the Eastern blotting technique for analysis of saikosaponin compounds is a simple method for quality-control monitoring of Bupleuri radix and of Kampo formulations containing Bupleuri radix.     

Clonal and parallel evolution of primary lung cancers and their metastases revealed by molecular dissection of cancer cells.

PURPOSE: Several models of cancer progression, including clonal evolution, parallel evolution, and same-gene models, have been proposed to date. The purpose of this study is to investigate the authenticity of these models by comparison of accumulated genetic alterations between primary and corresponding metastatic lung cancers. EXPERIMENTAL DESIGN: A whole-genome allelic imbalance scanning using a high-resolution single nucleotide polymorphism array and mutational analysis of the p53, EGFR, and KRAS genes were done on eight sets of primary and metastatic lung cancers. Based on the genotype data, the natural history of each case was deduced, and candidate metastasis suppressor loci were determined. RESULTS: Five to 20 chromosomal regions showed allelic imbalance in each tumor. Accumulated genetic alterations were similar between primary and corresponding metastatic tumors, and the majority(>67%) of genetic alterations detected in metastatic tumors was also detected in the corresponding primary tumors. On the other hand, in seven of the eight cases, there were genetic alterations accumulated only in metastatic tumors. Among these alterations, allelic imbalances at chromosome 11p15 and 11p11-p13 regions were the most frequent ones (4 of 8, 50%). Likewise, four cases showed genetic alterations detected only in primary tumors. CONCLUSIONS: The natural history of each case indicated that the process of metastasis varies among cases, and that all three models are applicable to lung cancer progression. According to the clonal and parallel evolution models, it is possible that a metastasis suppressor gene(s) for lung cancer is present on chromosome 11p.     

In Vivo Molecular Imaging to Diagnose and Subtype Tumors through Receptor-Targeted Optically Labeled Monoclonal Antibodies

Molecular imaging of cell surface receptors can potentially diagnose tumors based on their distinct expression profiles. Using multifilter spectrally resolved optical imaging with three fluorescently labeled antibodies, we simultaneously imaged three different cell surface receptors to distinguish tumor types noninvasively. We selected tumors overexpressing different subtypes of EGFR receptor: HER-1 (A431) and HER-2 (NIH3T3/HER2⁺), or interleukin-2 receptor α-subunit receptor (IL-2Rα; SP2/Tac). After tumor establishment, a cocktail of three fluorescently labeled monoclonal antibodies was injected: cetuximab-Cy5 (targetingHER-1), trastuzumab-Cy7(HER-2),anddaclizumab-AlexaFluor-700 (IL-2Ra). Optical fluorescence imaging was performed after 24 hours with both a red filter set and three successive filter sets (yellow, red, and deep red). Spectrally resolved imaging of 10 mice clearly distinguished A431, NIH3T3/HER2⁺, and SP2-Tac tumors based on their distinct optical spectra. Three-filter sets significantly increased the signal-to-background ratio compared to a single-filter set by reducing the background signal, thus significantly improving the differentiation of each of the receptors targeted (P < .022). In conclusion, following multifilter spectrally resolved imaging, different tumor types can be simultaneously distinguished and diagnosed in vivo. Multiple filter sets increase the signal-to-noise ratio by substantially reducing the background signal, and may allow more optical dyes to be resolved within the narrow limits of the near-infrared spectrum.