Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen

BACKGROUND: Early growth response factor-1 (Egr-1) plays an important role in regulating multiple factors involved in the progression of vascular lesions. This study examined our hypothesis that Egr-1 plays a critical role in the early stage of chronic cardiac allograft rejection and in the proliferation of the smooth muscle cell response to alloantigen. MATERIALS AND METHODS: Antisense Egr-1 oligodeoxynucleotide (ODN) was ex vivo gene transfected into the donor hearts from DBA/2 mice, followed by heterotopic allografting into B10.D2 recipients. The allografts were harvested on day 30. Egr-1 and its target molecules, such as platelet-derived growth factor (PDGF)-A, basic fibroblastic growth factor (bFGF), vascular cell adhesion molecule (VCAM)-1, transforming growth factor (TGF)-beta and nonmuscle myosin heavy chain B (SMemb), were identified immunohistochemically, and the percentage of the lumen occluded by the intima was calculated. For the cell proliferation assay, sensitized T cells were harvested from B10.D2 recipients as stimulator and then added to the SMCs, which were harvested from DBA/2 mouse aorta. Cellular proliferation was measured and Egr-1 and its target gene expression were examined by real-time RT-PCR. RESULTS: Egr-1 and its target genes were expressed in the thickened intima from untreated recipients. Egr-1 antisense ODN inhibited not only Egr-1 expression but also its target genes and significantly suppressed intimal thickening of coronary arteries. Egr-1 antisense ODN also significantly inhibited cell proliferation and expressions of Egr-1 and Egr-1 target genes in a mixed cell culture model. CONCLUSION: We conclude that Egr-1 plays an important role in the formation of the cardiac allograft vasculopathy responding to alloantigens.     

fMRI study of recognition of facial expressions in high-functioning autistic patients

Autistic disorder is associated with deficits in social function. The disorder may be related to dysfunction in the brain regions that are involved in the process of recognising facial expressions of other persons. Using fMRI, we investigated whether autistic patients with relatively high IQ would have different brain activation on the tasks of recognition of facial expressions (i.e. faces expressing disgust, fear, and happiness) compared with normal control subjects. In disgust and fear recognition tasks, there were different patterns of brain activation in the cortico-limbic neural circuits qbetween autistic and normal groups. Patients with autistic disorder may have difficulty in grasping facially expressed qemotions in others, and thereby cannot manipulate the interpersonally derived information.     

Anatomical analysis of the human lacrimal drainage pathway under an operating microscope

Mesoscopic structures of the lacrimal drainage pathway were observed under an operating microscope in six cases of 5 adult cadavers. In all these cases the upper and lower canaliculi fused to form the common canaliculus. Two cases with a large common canaliculus showed large projections of mucosa which reduced the inner space of the common canaliculus. The remaining 4 cases with a small common canaliculus did not show any projections. These findings indicate that the human lacrimal system can function physiologically through a small narrow space of the common canaliculus.Abbreviation DSI direct silicone intubation     

Effects of Viscous Hyaluronate–Sodium Solutions on the Nasal Absorption of Vasopressin and An Analogue

The effects of viscous solutions of hyaluronate-sodium of various average molecular weights (MW) on the nasal absorption of vasopressin (AVP) and its analogue, l-deamino-8-D-arginine vasopressin (l-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 × 10⁵ daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 × 10⁴ daltons were not effective. The enhancing effects on the nasal absorption of AVP and l-d-8-DAVP were dependent on the concentration in the range of 0–1.5% (w/v) hyaluronate (MW 1.4 × 10⁶ daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and l-d-8-DAVP in hyaluronate solutions (MW 1.4 × 10⁶ and 2 × 10⁶ daltons) increased more than 2- and 1.6-fold as compared to nasal administration of AVP and 1-d-8-DAVP in buffer solutions (pH 7.0), respectively. Hyaluronate solution (MW 1.4 × 10⁶ daltons) did not affect the ciliary beat frequency of rabbit nasal mucosal membranes in vitro. Therefore, hyaluronate solution may be useful as a vehicle for nasal delivery of AVP and l-d-8-DAVP.     

Ablation therapy guided by contrast-enhanced sonography with Sonazoid for hepatocellular carcinoma lesions not detected by conventional sonography.

OBJECTIVE: We evaluated the usefulness of contrast-enhanced harmonic gray scale sonography with a newly developed sonographic contrast medium as a means of guidance for percutaneous ablation therapy of hepatocellular carcinoma lesions not detected by conventional sonography. METHODS: We examined 85 patients with 108 hepatocellular carcinoma lesions that were identified as hypervascular by multidetector-row computed tomography by using contrast-enhanced harmonic gray scale sonography after injection of Sonazoid (GE Healthcare, Oslo, Norway), a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent. We scanned the whole liver by this modality at a low mechanical index in the late phase to detect lesions not detected by conventional sonography and then scanned the lesions again by this modality at a high mechanical index to visualize tumor vessels and enhancement. We also performed percutaneous ablation therapy guided by this modality to treat viable hepatocellular carcinoma lesions that could not be detected by conventional sonography. RESULTS: Conventional sonography identified 90 (83%) of 108 hepatocellular carcinoma lesions; 15 (14%) additional viable lesions not detected by conventional sonography were detected in the late phase of contrast-enhanced harmonic gray scale sonography at a low mechanical index, and tumor vessels and enhancement were observed in the late phase at a high mechanical index. Contrast-enhanced harmonic gray scale sonography diagnosed 105 (97%) of the 108 viable hepatocellular carcinoma lesions, and 14 (93%) of the 15 lesions not detected by conventional sonography were successfully treated by percutaneous ablation therapy guided by this modality. CONCLUSIONS: Contrast-enhanced harmonic gray scale sonography is useful for guidance of percutaneous ablation therapy of hepatocellular carcinoma lesions not detected by conventional sonography.     

Clinical characteristics of Japanese reflux esophagitis patients as determined by Los Angeles classification

BACKGROUND: Recent studies have shown that the number of patients with reflux esophagitis is increasing in Japan, but the prevalence and risk factors associated with reflux esophagitis in Japanese patients are not well defined. METHODS: By using all endoscopic records in the Katta General Hospital from April through to September 1999, we identified 392 patients. We examined the Los Angeles classification, peptic ulcer, gastric mucosal atrophy, hiatal hernia and other medical variable factors for their contribution to esophagitis in the patients. RESULTS: Patients (13.8%) were diagnosed as having reflux esophagitis with a mucosal break. In a multivariate analysis, reflux esophagitis was associated with hiatal hernia (odds ratio (OR) 2.276, 95% confidence interval (CI) 1.164-4.450), with patients over 65 years of age (OR 2.521, 95% CI 1.238-5.134) and the open type of gastric mucosal atrophy (OR 0.420, 95% CI 0.225-0.785). There was no significant difference between esophagitis and Helicobacter pylori infection and peptic ulcer. CONCLUSIONS: We observed that age, hiatal hernia and a lower rate of gastric mucosal atrophy were associated with the proportion of mucosal breaks accompanying esophagitis.     

In vivo study on cross talk between inducible nitric-oxide synthase and cyclooxygenase in rat gastric mucosa: effect of cyclooxygenase activity on nitric oxide production

The integrity of gastric mucosa during endotoxemia is maintained by the balance of inflammatory mediators, such as prostanoids originated from cyclooxygenase-2 (COX-2) and nitric oxide (NO) from inducible nitric-oxide synthase (iNOS). Thus, we elucidated in vivo cross talk between prostanoids and NO in gastric mucosa during endotoxemia, using an iNOS-specific inhibitor, N-(3-(aminomethyl)benzyl)acetamidine (1400W); a nonspecific COX inhibitor, indomethacin; and a COX-2-specific inhibitor, N-(2-[cyclohexyloxy]-4-nitrophenyl)methanesulfonamide (NS-398). Gastric mucosal NO and prostaglandin E2 (PGE2), a predominant product of COX, expressed as mean +/- S.D. of five rats per group, were assayed by electron paramagnetic resonance spectrometry and enzyme immunoassay technique, respectively. The levels of NO and PGE2 increased gradually up to 6 h after administration of bacterial lipopolysaccharide (LPS) (NO: control, 0.35 +/- 0.16; 6 h, 13.3 +/- 3.3 nmol/g tissue/30 min; and PGE2: control, 288 +/- 16; 6 h, 806 +/- 15 pg/g tissue). Pretreatment with 1400W decreased the increase in NO level without any effect on the PGE2 level (NO, 4.0 +/- 0.4 nmol/g tissue/30 min; PGE2, 788 +/- 26 pg/g tissue). In contrast, treatment with indomethacin and NS-398 inhibited not only PGE2 level but also NO level in a dose-dependent manner without any significant effect on both iNOS and COX protein and mRNA expression. These results demonstrate that in the LPS-treated rat gastric mucosa, PGE2 enhances the release of NO after activation of iNOS, although NO produced by iNOS does not stimulate the release of PGE2 by COXs. The effect of COX activity on iNOS-NO pathway can be important in the regulation of gastric mucosal integrity in inflammatory states.     

The results of in situ saphenous vein bypass for infrainguinal arterial reconstruction: Comparison between two types of valvulotomes

PURPOSE:

To evaluate the authors’ experiences with in situ saphenous vein bypasses that were performed using two types of valvulotomes and to respectively compare their efficacy on the basis of the operative outcomes.

METHODS:

Between June 1993 and December 2008, 103 constructive in situ saphenous vein bypasses were performed, of which 53 were performed between 1993 and 2000 using an Insitucat valvulotome (B Braun Melsungen AG, Germany), and 50 were performed between 2000 and 2008 using a LeMaitre valvulotome (LeMaitre Vascular Inc, USA).

RESULTS:

There were no statistical differences with regard to age, sex and bypass procedures between the two groups. Critical limb ischemia (P=0.021) and diabetes (P=0.005) were more frequent in the LeMaitre group than the Insitucat group. Intraoperative graft revisions (P=0.079) and graft spasms (P=0.638) were less frequent in the LeMaitre group. Graft failures in the perioperative period or within the first year were less frequent in the LeMaitre group. The five-year cumulative primary patency rates were 63.2% and 59.8% in the LeMaitre and Insitucat groups, respectively (χ²=0.390, not significant). The five-year cumulative secondary patency rates were 91.9% and 81.7% in the LeMaitre and Insitucat groups, respectively (χ²=2.690, not significant).

CONCLUSIONS:

The results suggested that there were no significant differences in the outcome and adverse effects between the two types of valvulotomes for in situ saphenous vein bypass.