APOE polymorphism and diabetic nephropathy

Epidemiological studies suggest the existence of a genetic susceptibility to the development of diabetic nephropathy. The apolipoprotein E gene (APOE), which is well known to have a polymorphism (ε2, ε3, and ε4) in exon 4, has been considered a candidate gene susceptible to this complication, because this variation was reportedly involved in lipid metabolism. To date, numerous case–control studies in patients with type 1 and type 2 diabetes have been reported. Although the ε2 allele of the APOE polymorphism tends to be associated with an increased risk for diabetic nephropathy, the results of these case–control comparisons are conflicting. However, a family-based study (the transmission/disequilibrium test) provided strong evidence that the ε2 allele was preferentially transmitted to patients with diabetic nephropathy but not transmitted to those without it. Several prospective follow-up studies also reported an increased risk for progression to higher stages of diabetic nephropathy for the ε2 carriers. Furthermore, two recent meta-analyses reported that the ε2 allele is associated with a risk for diabetic nephropathy. Based on the results of these studies, the ε2 allele of the APOE polymorphism seems to be a genetic risk factor for diabetic nephropathy susceptibility. However, this genetic effect only accounts for a small proportion of this complication, and the mechanism remains unclear at present. Further studies are needed to explore whether genotyping of the APOE polymorphism in patients with diabetes is of value for better management in clinical practice.     

Modified Cranialization and Secondary Cranioplasty for Frontal Sinus Infection after Craniotomy: Technical Note

Frontal sinus infection after incorrect treatment of an opened frontal sinus may require extended approaches. This article aims to introduce modified cranialization technique and secondary cranioplasty for frontal sinus infection involving the frontal sinus outflow tract after craniotomy. Eight patients with delayed onset frontal sinus infection involving frontal outflow tract after craniotomy were treated from 2008 to 2012. Debridement and cranialization involving the elimination of the frontal outflow tract was performed. Unilateral sinus cranialization combined with reduction of the non-affected contralateral sinus was carried out for the patients with unilateral sinusitis. A pericranial-frontalis muscle flap was used to separate the intracranial and extracranial spaces. Secondary cranioplasty with hydroxyapatite was performed approximately 3 months after the cranialization. The patients’ original conditions included brain tumors (n = 3), frontal sinus fractures (n = 2), and subarachnoid hemorrhage (n = 3). The mean interval between the initial treatment and the onset of sinus infection was 23 years. The frontal sinus infection was bilateral in six cases and unilateral in two cases. Frontal sinus outflow tract was involved in sinus infection in every case. None of the patients suffered recurrent rhinogenic infections within the follow-up period (mean = 35 months) after the secondary cranioplasty. Aesthetic results were satisfactory in every case. Modified cranialization involving elimination of the frontal outflow tract is an alternative method for the patients with pathology in the frontal outflow tract after frontal craniotomy. Secondary cranioplasty provides an esthetically pleasing appearance in such cases.     

Poor responses to tyrosine kinase inhibitors in a child with precursor B‐cell acute lymphoblastic leukemia with SNX2‐ABL1 chimeric transcript

In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2‐ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2‐ABL1 fusion exhibited a BCR‐ABL1+ ALL‐like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype‐based treatment stratification for patients with SNX2‐ABL1 fusion.     

The effects of low-level laser irradiation on bone tissue in diabetic rats

Diabetes mellitus (DM) leads to a decrease in bone mass and increase the risk of osteoporosis and in this context, many treatments have shown to accelerate bone metabolism. It seems that low-level laser therapy (LLLT) is able of stimulating osteoblast activity and produced increased biomechanical properties. However, its effects on bone in diabetic rats are not fully elucidated. The aim of this study was to evaluate the effects of LLLT on bone formation, immunoexpression of osteogenic factors, biomechanical properties and densitometric parameters in diabetic rats. Thirty male Wistar rats were randomly distributed into three experimental groups: control group, diabetic group, and laser-treated diabetic group. DM was induced by streptozotocin (STZ) and after 1 week laser treatment started. An 830-nm laser was used, performed for 18 sessions, during 6 weeks. At the end of the experiment, animals were euthanized and tibias and femurs were defleshed for analysis. Extensive resorptive areas as a result of osteoclasts activity were noticed in DG when compared to control. Laser-treated animals showed an increased cortical area. The immunohistochemical analysis revealed that LLLT produced an increased RUNX-2 expression compared to other groups. Similar RANK-L immunoexpression was observed for all experimental groups. In addition, laser irradiation produced a statistically increase in fracture force, bone mineral content (BMC) and bone mineral density compared to DG. The results of this study indicate that the STZ model was efficient in inducing DM 1 and producing a decrease in cortical diameter, biomechanical properties and in densitometric variables. In addition, it seems that LLLT stimulated bone metabolism, decreased resorptive areas, increased RUNX-2 expression, cortical area, fracture force, BMD, and BMC. Further studies should be developed to provide additional information concerning the mechanisms of action of laser therapy in diabetic bone in experimental and clinical trials.     

Advances in balloon endoscopes

In September 2003, a double-balloon endoscope (DBE) composed of balloons attached to a scope and an overtube was released in Japan prior to becoming available in other parts of the world. The DBE was developed by Dr. Yamamoto (1), and 5 different types of scopes with different uses have already been marketed. In April 2007, a single-balloon small intestinal endoscope was released with a balloon attached only to the overtube as a subsequent model. This article presents a detailed account of the development of these scopes up to the present time.     

Programmable cells: interfacing natural and engineered gene networks

Novel cellular behaviors and characteristics can be obtained by coupling engineered gene networks to the cell's natural regulatory circuitry through appropriately designed input and output interfaces. Here, we demonstrate how an engineered genetic circuit can be used to construct cells that respond to biological signals in a predetermined and programmable fashion. We employ a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: (i) the SOS signaling pathway responding to DNA damage, and (ii) a transgenic quorum sensing signaling pathway from Vibrio fischeri. The genetic toggle switch endows these strains with binary response dynamics and an epigenetic inheritance that supports a persistent phenotypic alteration in response to transient signals. These features are exploited to engineer cells that form biofilms in response to DNA-damaging agents and cells that activate protein synthesis when the cell population reaches a critical density. Our work represents a step toward the development of "plug-and-play" genetic circuitry that can be used to create cells with programmable behaviors.     

Age-related changes of NGF, BDNF, parvalbumin and neuronal nitric oxide synthase immunoreactivity in the mouse hippocampal CA1 sector

We investigated the age-related alterations in nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), parvalbumin and neuronal nitric oxide synthase (nNOS) immunoreactivity of the mouse hippocampal CA1 sector. NGF and BDNF immunoreactivity was unchanged in the hippocampal CA1 pyramidal neurons from 2 to 50-59 weeks of birth. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector from 40-42 to 50-59 weeks of birth. On the other hand, the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. Our results indicate that NGF and BDNF immunoreactivity was unaltered in the hippocampal CA1 pyramidal neurons during aging processes. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector during aging processes. The present study also shows that the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. These results demonstrate that the expression of glial NGF and BDNF may play a key role for helping survival and maintenance of pyramidal neurons and neuronal functions in the hippocampal CA1 sector during aging processes. Furthermore, our findings suggest that parvalbumin- and nNOS-positive interneurons in the hippocampal CA1 sector are resistant to aging processes. Moreover, our findings suggest that nitric oxide synthesized by the nNOS may play some role for neuronal growth during postnatal development.     

Molecular investigation of pathogenic factors of suspected-diarrheogenic Escherichia coli isolates from patients feces

One hundred fifty-one O serotypable Escherichia coli strains which were assumed diarrheogenic E. coli among 2,240 strains of E. coli isolated from the in- and outpatients stools with or without gastrointestinal symptoms at Kyorin University Hospital from February 1994 to September 1996 were examined for the relationship between the possession of eight pathogenic factor-related genes and gastrointestinal symptoms of the patients using the polymerase chain reaction (PCR) for these strains. The rate of possession of pathogenic factor-related genes in the E. coli examined was 20.5% (31 strains) and gastrointestinal symptoms were found in all the patients with these strains except one. In the patients without gastrointestinal symptoms, E. coli isolates that possesses these genes was detected in only one case during 61 cases. The respective genes detected were eaeA and astA in each 14 strains, VT1 in 6, VT2 in 5, ST1b in 4, aggR in 3 and LT in 2, ST1a and invE gene was not detected. In particular, the O157 strains were found in 55.6% (5/9 strains) for these genes, and individual strains had VT1, VT2, eaeA and astA genes simultaneously. In contrast, none of these related genes was found in 9 strains of enteroinvasive serotype but enteropathogenic E. coli-related genes were found in 3 strains. The rate of possession of the genes related to enterotoxigenic E. coli, O159 which was most frequently isolated was low as 2.3% (1/43 strains, astA gene) and there were strains showing low correlation to the state of possession of the genes with the O serotype. Since the prevalence of the gastrointestinal symptoms is clearly high for the case which possesses the strain of which the pathogenic factor-related gene was detected, it was suggested that detection of pathogenic factor-related genes in E. coli isolates from feces using the PCR could be an effective means to decide whether the bacteria concerned was a causal bacteria or not in clinical practice.