Hepatocyte growth factor attenuates cerebral ischemia-induced learning dysfunction

Hepatocyte growth factor (HGF) acts as an organotropic factor for regeneration and protection in various organs and has the ability to attenuate cerebral ischemia-induced cell death. However, the effect of HGF on learning and memory function after a cerebral ischemic event is unknown. We demonstrate here that administration of human recombinant HGF (hrHGF) into the ventricle reduced the prolongation of the escape latency in the acquisition and retention tests in the water maze task on days 12-28 after microsphere embolism-induced cerebral ischemia. In addition, disruption of the blood-brain barrier at the early stage after microsphere embolism, which was determined by FITC-albumin leakage, was markedly reduced by treatment with hrHGF. We demonstrated that this effect of hrHGF on the blood-brain barrier was associated with protection against the apoptotic death of the cerebral endothelial cells at the early stage after the ischemia. These results suggest that hrHGF can prevent the learning and memory dysfunction soon after sustained cerebral ischemia by protecting against injury to the endothelial cells. The use of HGF may be a potent strategy for the treatment of cerebrovascular diseases, including cerebral infarct and vascular dementia.     

Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection.     

Evaluation of absolute configuration of naphthylphenyl-substituted oligosilanes by CD exciton chirality method

Absolute configurations of methylnaphthylphenyl-substituted oligosilanes, MeNpPhSi*SiMeR(1)R(2) [2 (R(1), R(2)=Me), 3 (R(1)=Me, R(2)=Ph), 4 (R(1), R(2)=Ph), and 5 (R(1)=Me, R(2)=SiMe(3))] were predicted by circular dichroism (CD) exciton chirality method. The sigma-pi conjugation effect of oligosilylene units (sigma-linkage) with pi-electron systems caused an intense red-shift of (1)L(a,Ph) transition band of the oligosilanes as shown in UV/VIS and made it possible to observe clear CD exciton chirality between the two aromatic chromophores on chiral silicon atom.     

Impact of Human Genome Project on treatment of frail and edentulous patients

Objective: Because of ongoing increases in life expectancy and deferment of edentulousness to older age, dentists are facing a different challenge to satisfy elderly denture wearers with a higher prevalence of chronic diseases. This discussion introduces the Human Genome databases as novel and powerful resources to re‐examine the core problems experienced by frail and edentulous patients. Background: Recent studies demonstrated that mandibular implant overdentures do not necessarily increase masticatory function, perception and satisfaction in denture wearers with adequate edentulous residual ridges. It has been demonstrated that the rate of edentulous residual ridge resorption significantly varies among individuals. The prognosis and cost‐effectiveness of denture treatment, with or without implants, may largely depend on how the edentulous ridge is maintained. However, reliable clinical methods permitting dentists to predict the long‐term health of the edentulous residual ridge are lacking. Materials and methods: With the completion of the Human Genome Project, the genomic sequence database from this multinational consortium will provide a unique resource to determine the genetic basis of similarity and diversity of humans. Results: One base pair in every 100 to 300 base pairs of the genome sequence varies among humans, suggesting that genetic diagnosis using the single nucleotide polymorphisms (SNPs) may provide a novel opportunity to differentiate our edentulous patients. Conclusions: Future dental service for the elderly will require a personalized care paradigm, using highly sensitive diagnostic technology such as SNP genomic analysis, for recommending the treatment with greatest potential benefit.     

T cells of atopic asthmatics preferentially infiltrate into human bronchial xenografts in SCID mice

T cells play an important role in the pathogenesis of bronchial asthma. However, it is not completely known how circulating lymphocytes infiltrate into the airways of asthmatic patients. Because SCID mice are unable to reject xenogenic transplants, many xenotransplant models using various human tissues have been developed. Therefore, to examine the interaction between bronchi and T lymphocytes of asthma, it may be possible to use the human bronchial xenograft and PBMC xenograft in SCID mice. We transplanted human bronchi into the subcutaneum of SCID mice and i.p. injected PBMCs that were obtained from patients with atopic asthma, atopic dermatitis and rheumatoid arthritis, and normal subjects (asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice). There was no difference in the percentage of CD3-, CD4-, CD8-, CD25-, CD45RO-, CD103-, and cutaneous lymphocyte Ag-positive cells in PBMCs among the patients with asthma, dermatitis, rheumatoid arthritis, and normal subjects, and CD3-positive cells in peripheral blood of asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice. The number of CD3-, CD4-, and CD8-positive cells in the xenografts of asthmatic huPBMC-SCID mice was higher than those of dermatitis, rheumatic, and normal huPBMC-SCID mice. IL-4 mRNA and IL-5 mRNA were significantly higher in the xenografts of asthmatic huPBMC-SCID mice than those in the xenografts of normal huPBMC-SCID mice, but there were no significant differences in the expressions of IL-2 mRNA or IFN-gamma mRNA between them. These findings suggest that T cells, especially Th2-type T cells, of asthmatics preferentially infiltrate into the human bronchi.