Vascular Endothelial Growth Factor–Bound Stents: Application of In Situ Capture Technology of Circulating Endothelial Progenitor Cells in Porcine Coronary Model

Objectives

We evaluated the in vivo performance of a newly devised vascular endothelial growth factor (VEGF)‐bound stent in a porcine coronary model.

Background

An anti‐CD34 antibody‐bound stent, which captures endothelial progenitor cells (EPCs) to accelerate tissue formation, did not reduce intimal hyperplasia. By targeting the VEGF receptor, which is expressed on endothelial‐lineage cells, we developed VEGF‐bound stents that may enable selective capture of EPCs followed by rapid endothelialization.

Methods

Metallic stents were first coated with poly‐(ethylene‐co‐vinyl alcohol), and then chemically bound with either VEGF or anti‐CD34 antibody. These stents were placed in porcine coronary arteries for up to 14 days. Stent surface was evaluated by immunohistochemistry and by scanning electron microscope (SEM).

Results

After 2‐day stenting with VEGF‐bound stents, small populations of KDR (VEGF receptor‐2)‐positive cells adhered to the stent struts. After 7‐ and 14‐day stenting, struts were fully covered with newly regenerated tissue. SEM images showed that the uniform tissue formed on struts was morphologically similar to native endothelium and was continuously connected with adjacent native endothelium. On the other hand, for the anti‐CD34 antibody‐bound stents, stent struts were rapidly covered by newly generated tissue that consisted of multicellular aggregates.

Conclusions

Compared with anti‐CD34 antibody‐bound stents, VEGF‐bound stents provide highly selective capture of EPCs, followed by rapid formation of intact endothelium tissue at an early period of stenting. These results suggest that VEGF‐bound stents could represent a promising therapeutic option for cardiovascular stenting, although further long‐term follow‐up experiment with double‐blinded fashion is needed prior to clinical application. (J Interven Cardiol 2014;27:63–72)

     

Job Demands,Job Resources,and Job Performance in Japanese Workers: A Cross-sectional Study

This study investigated the cross-sectional association of job demands (i.e., psychological demands) and job resources (i.e., decision latitude, supervisor support, co-worker support, and extrinsic reward) with job performance. A total of 1,198 workers (458 males and 740 females) from a manufacturing company in Japan completed a self-administered questionnaire that included the Job Content Questionnaire, Effort-Reward Imbalance Questionnaire, World Health Organization Health and Work Performance Questionnaire, and demographic survey. Hierarchical multiple regression analyses were conducted. After adjusting for demographic characteristics, decision latitude (β=0.107, p=0.001) and extrinsic reward (β=0.158, p<0.001) were positively and significantly associated with job performance while supervisor support (β=−0.102, p=0.002) was negatively and significantly associated with job performance. On the other hand, psychological demands or co-worker support was not significantly associated with job performance. These findings suggest that higher decision latitude and extrinsic reward enhance job performance among Japanese employees.     

Prognosis and pathological characteristics of five children with non-Shiga toxin-mediated hemolytic uremic syndrome

BACKGROUND: The three major signs of hemolytic uremic syndrome (HUS) are hemolytic anemia, thrombopenia and acute renal failure. HUS is classified into Shiga toxin-mediated HUS (Stx-HUS) and non-Shiga toxin-mediated HUS (nStx-HUS). The prognosis of nStx-HUS is reported to be less favorable than that of Stx-HUS. Although the association between the prognosis and pathological characteristics of HUS have been reported such that the prognosis was considered to be poor for thrombotic microangiopathy (TMA) with predominant arterial involvement (arterial TMA), good for TMA with predominant glomerular involvement (glomerular TMA) and dependent on the extent of necrosis in cases of renal cortical necrosis, it is not yet clear whether pathological findings are also related to the renal prognosis of nStx-HUS cases. Therefore the purpose of the present paper was to analyze renal biopsy findings and prognosis for five children with nStx-HUS. METHODS: Clinical records of five cases of nStx-HUS among 74 cases of diagnosed HUS were reviewed, and information and data were summarized. RESULTS: Histological examination of the kidney led to the diagnosis of arterial TMA in three cases, and glomerular TMA and severe renal cortical necrosis in one case each. Analysis of the relationship between renal histological findings and the prognosis found that three patients with arterial TMA and one patient with severe renal cortical necrosis later developed end-stage renal failure while one patient with glomerular TMA has continued to show normal renal function. CONCLUSIONS: These findings indicate that pathological findings are closely related to the prognosis in cases of nStx-HUS.     

Perspectives on phantom boarder symptom

Phantom boarder symptom (PBS) is a hallucinatory and delusional syndrome that tends to occur in the elderly, in which the patient imagines that someone uninvited is living in their home. This article provides an overview of the historical background that has led to the current focus on PBS as a single symptom, from its classification as late paraphrenia to its being recognized as a type of misidentification, and discusses classification problems and PBS subclassifications. In addition, the results of our own investigation of PBS, which focused on PBS in senile dementia, support the findings of previous studies, such as the absence of a relationship between dementia severity and the occurrence of delusion. The discussion therefore focuses on the psychosocial factors that serve as the mechanism of PBS onset, and directions and possibilities for therapy are suggested.     

Peritoneoscopic Findings of Autoimmune Hepatitis

Abstract: To clarify the morphologic differences between hepatitis C virus (HCVI-negative autoimmune hepatitis (AIH) and HCV-positive AIH, peritoneoscopic findings were studied. Among twenty three patients with AIH according to the Japanese criteria (1992), 15 were HCV-negative and 8 were HCV-positive. The terms grooved depression, coarse depression, coarse elevation, coarse undulation, and round-shaped reddish marking (RM) were used in this study to evaluate the peritoneoscopic findings. Grooved depressions, coarse depressions, coarse elevations, coarse undulations and round-shaped RMs were all common findings (53%, 87%, 73%, 80%, and 80%, respectively) in HCV-negative AIH patients, but they were less common (13%, 25%, 13%, 13%, and 0%, respectively) in HCV-positive AIH patients. This study revealed that HCV-negative AIH patients had different peritoneoscopic findings from HCV-positive AIH patients. Thus HCV-negative AIH may be typical AIH, and HCV-positive AIH may essentially be a subset of type C chronic hepatitis.     

Defective suppressor function of spleen cells by neonatal thymectomy and persistence of experimental auto-immune hepatitis in mice

The effects of neonatal thymectomy on a model of auto-immune hepatitis prepared by immunizing A/J mice with syngeneic crude liver proteins were studied. Hepatitis was more severe in neonatally thymectomized mice (Group B) than in non-thymectomized controls (Group A). Changes in the hepatic lobules were reduced in both groups 3 months after the final immunization, but inflammation around the portal areas tended to persist in Group B; only this group showed frequent infiltration of mononuclear cells accompanied by destruction of the limiting plate in the portal area. The serum level of auto-antibody to liver-specific membrane lipoprotein complex (LSP) and delayed-type hypersensitivity (DTH) to LSP were higher in Group B than in Group A. The auto-antibody to LSP was positive in both groups 3 months after the final immunization. Although it was significantly reduced in Group A compared with the level 3 days after the final immunization, it remained high in Group B. Liver damage, production of the auto-antibody to LSP and DTH to LSP were reduced by adoptive transfer of normal murine spleen cells, but the spleen cells of neonatally thymectomized mice showed no such effects. These results suggest that normal spleen cells possess the capability of suppressing auto-immune hepatitis, and the defect of this capability due to T-cell dysfunction by neonatal thymectomy contributes to the promotion and persistence of auto-immune hepatitis.     

Point mutation in precore region of hepatitis B virus: Sequential changes from 'wild' to 'mutant'

One point mutation to make a stop codon in the precore (pre-C) region of the hepatitis B virus DNA in anti-HBe-positive patients has been reported recently. This mutation disturbs the formation of the pre-C protein that is processed to make HBeAg. The relationship between the point mutation and HBe antigen antibody status was investigated in B-viral liver diseases. The pre-C region was amplified by a polymerase chain reaction (PCR) method and the nucleotide sequences were determined by a direct sequencing method. In seven cases who were persistently HBeAg-positive, the wild type (no mutation in pre-C region) was detected in all. In 20 cases who were anti-HBeAg-positive at diagnosis, the mutant type (point mutation at nucleotide 1896 in pre-C region, which makes a stop codon) was detected in 16 cases and the wild type in two cases. In HBe seroconversion (SC) cases, the types of virus were investigated in serial blood samples. No mutant type was detected in initial sera during the HBeAg-positive period. In two ‘natural’ SC cases, the mutant type appeared before anti-HBe formation. However, in three anti-viral ‘drug-induced’ SC cases, the mutant type appeared after the formation of anti-HBe. In two ‘reversed’ seroconversion cases only the wild type was detected throughout the follow-up period. These data suggest that the appearance of a pre-C mutant may help to predict seroconversion from HBeAg to anti-HBe and may help distinguish ‘natural’ and ‘drug-induced’ seroconversion of HBeAg.     

Synthesis and stabilization of amino and carboxy terminal constrained collagenous peptides

Short collagenous peptides cross-linked at their amino and carboxy termini with Lys-Lys-dimer template(s) were synthesized, and the effect of the cross-linking on their stabilities was investigated by thermal denaturation experiments. Two chemoselective ligations were used for the construction of the amino and the carboxy cross-linked peptides. The thermal transition temperature (T_m) and the standard free energies (ΔG°) of the cross-linked collagenous peptides increased, and the thermal stabilization effect corresponded to an elongation by two units of the Gly-Pro-Hyp triad. The van't Hoff enthalpy (ΔH°) and the entropy (ΔS°) values of the cross-linked peptides increased with chain elongation, although the increments were smaller than those of the linear peptides. When the same chain lengths were compared, the ΔH° was increased and the ΔS° was nearly the same or increased by the cross-linking. These results suggest that the cross-linking of the collagenous peptides with the Lys-Lys-dimer template(s) for stabilization contributes to the enthalpic effect, rather than the entropic effect.     

Two types of left ventricular wall motion abnormalities with distinct clinical features in patients with hypertrophic cardiomyopathy

During the long-term follow-up of patients with hypertrophiccardiomyopathy (HCM), some patients develop left ventricular(LV) wall motion abnormalities in the absence of fixed coronaryartery disease. The purpose of this study is to clarify whichclinical features in patients with HCM seem to influence gradualdevelopment of LV wall motion abnormalities over an extendedperiod of time. The study investigates the incidence, mechanismand predictors of these abnormalities. In this retrospectivestudy of 162 patients with HCM, followed-up for an average of13.3 years, we focused our attention on 16 patients who graduallydeveloped two different forms of LV wall motion abnormality.In 11 of these 16 patients, apical segmental dysfunction withmidzone obstruction was recognized; the remaining five patientsshowed generalized hypokinesis, as seen in dilated cardiomyopathy.The 11 patients with apical segmental dysfunction presentedwith extensive apical hypertrophy reaching the midventricularlevel at first examination. The five patients with generalizedhypokinesis showed a slight decrease in LV contractility andreduced localized antero-apical wall motion even at initialexamination. None of the patients in either group developedthe other group's features during their clinical course. These two groups had different initial manifestations and pursueddifferent clinical courses, suggesting that the underlying mechanismscausing wall motion abnormalities are different.