Increased expression of HDJ-2 (hsp40) in carotid artery atherosclerosis: a novel heat shock protein associated with luminal stenosis and plaque ulceration.

PURPOSE: Evidence suggests that both humoral and cellular autoimmune processes directed toward heat shock proteins (hsp) contribute to the pathogenesis of atherosclerosis. We characterized a human hsp distinct from those previously characterized in atherosclerotic lesions, termed HDJ-2. METHODS: To determine the role of HDJ-2 in atherosclerosis, we compared the level of HDJ-2 mRNA expression with the level of hsp60 and hsp70 mRNA expression in 26 carotid endarterectomy specimens and 17 normal arteries. The level of expression of HDJ-2 mRNA was also correlated to the presence of plaque ulceration and the degree of luminal stenosis associated with the lesion. RESULTS: The expression of HDJ-2 and hsp70 was significantly higher in carotid artery plaques as compared with normal arteries: HDJ-2, 6.7 +/- 1.6 vs 0.1 +/- 0.04, (P =.001); hsp70, 9.5 +/- 0.9 vs 3.7 +/- 0.8, (P =.002). There was no significant difference in hsp60 expression between carotid artery plaques and normal arteries (21.0 +/- 0.9 vs 20.6 +/- 0.8, P =.65). Increased HDJ-2 expression in carotid artery plaques was independent of hsp70 (Pearson correlation, r = 0.11; Bartlett chi(2) analysis, P =.71). Within the ulcerated plaque group, there was a correlation between degree of stenosis and high HDJ-2 mRNA expression (r = 0.896, P =.016). However, there was no correlation between degree of stenosis and high HDJ-2 mRNA expression within the nonulcerated plaque group (r = 0.530, P =.076) or within the entire group of patients (r = 0.0085, P =.97). CONCLUSION: These results demonstrate that expression of HDJ-2 is significantly increased in atherosclerotic carotid artery plaques as compared with hsp60 and hsp70 and correlates with luminal stenosis in ulcerated atherosclerotic carotid artery plaques.

Transrectal ultrasound assessment of murine aorta and iliac arteries.

Recent research in arterial aneurysm formation has focused on animal model development. Mice are an ideal experimental organism due to their short life cycle, prolific progeny, and extensively studied genome. Most experiments require the sacrifice of the mice to observe and assess any morphological changes. Noninvasive or minimally invasive imaging is limited due to the relatively small size of the structures. The development of such a technique, therefore, is especially useful for allowing repeated measurement without sacrificing the mice. We introduce a novel technique of imaging and measuring the aorta, the aorta/inferior vena cava complex, and the right and the left common iliac artery/vein complex by the use of an intravascular ultrasound catheter. The catheter is inserted through the anus and rectum and into the sigmoid and left colon, where the aorta can be observed to fluctuate at approximately 500 beats/min. The aortic bifurcation can also be observed. The diameters of the aorta and the inferior vena cava were measured first with the transrectal ultrasound technique and then with direct visualization upon laparotomy for 10 mice. This revealed a percentage error between 13.7 and 14.2% for this novel technique. Fifteen more sets of vessel measurements were also made with 8 male and 7 female mice. The results demonstrated a correlation between vessel size and body weight in male but not female mice and suggested an intersex difference in vessel growth rate. We conclude that transrectal ultrasound is a useful tool in imaging and measuring the murine aorta and its bifurcation.

Intercellular adhesion molecule-1/leukocyte function associated antigen-1 blockade inhibits alloantigen specific human T cell effector functions without inducing anergy.

BACKGROUND: Intercellular adhesion molecule (ICAM-1) is important in leukocyte adhesion-dependent events and some data suggest that ICAM-1 provides T cell costimulation. We anlayzed the role of the ICAM-1 and leukocyte function associated antigen-1 (LFA-1) interaction in human T cell alloreactivity in vitro. METHODS: Allo-antigen-induced T cell proliferation and cytotoxic T lymphocyte lytic activity were assessed by mixed lymphocyte reaction assay and 51 Chromium release assay, respectively. Immunostaining and flow cytometry were used to assess the expression of receptors on activated T cells. RESULTS: Alloantigen-induced T cell proliferation and cytotoxic T lymphocyte activity were markedly inhibited by antibodies to ICAM-1 and LFA-1. These antibodies had to be present at the time of initial T cell receptor/antigen engagement to inhibit proliferation. Neither IL-2 nor IL-4 were involved in the observed inhibition by antibodies. Inhibition was not associated with altered cell surface expression of receptors such as CD3, CD4, ICAM-1, LFA-1, CD25, and HLA-DR however, these antibodies did impede the ability of generation of functionally active T cells. Interestingly, these antibodies inhibited soluble, but not immobilized OKT3-induced proliferation of peripheral blood leukocytes. Antibody-mediated inhibition of proliferation failed to impair the ability of T cells to subsequently proliferate in response to stimulation by the original or third party alloantigen or mobilize [Ca++]i in response to CD3 or LFA-1 receptor ligation. CONCLUSIONS: These data demonstrate that blockade of ICAM-1/LFA-1 binding at the time of allorecognition potently blocks initial T cell effector functions that could be due to lack of effective T cell/APC engagement.

Intravascular ultrasound-guided vena cava filter placement.

PURPOSE: To report a technique for the insertion of an inferior vena cava (IVC) filter under intravascular ultrasound (IVUS) guidance. TECHNIQUE: Using a Seldinger technique, a single groin puncture provides the access for IVUS interrogation of the IVC. After the anatomy is defined with IVUS, the same guidewire is used for percutaneous IVC filter insertion. Intraoperative fluoroscopy, used as a backup, corroborates the proposed insertion location before deployment of the device. Postoperative flat-plate abdominal radiographs are used to confirm satisfactory position. IVC filters have been successfully placed in 9 patients with no complications related to IVUS-guided insertion. CONCLUSIONS: Intraluminal IVC interrogation using IVUS is ideally suited for the proper deployment of an IVC filter. The deployment of IVC filters under IVUS has the potential to further simplify an established therapy for deep venous thrombosis and pulmonary embolism.

Natural history of composite sequential bypass: ten years' experience.

BACKGROUND: We previously reported 48-month patency rates of composite sequential bypass (CSB) approaching 60%. Yet, extended patency and limb salvage rates are unknown. HYPOTHESIS: Long-term patency and limb salvage rates of CSB are affected by sex, bypass configuration, and warfarin therapy. DESIGN: Medical records of all patients who underwent CSB during a 10-year period were retrospectively reviewed. SETTING: A referral center for the Chicago, Ill, region. PATIENTS: One hundred consecutive patients (mean age, 68.8 years; 57% were men and 49% had diabetes) undergoing 102 CSBs for limb salvage (ulcer, 43%; rest pain, 39%; and gangrene, 18%) from January 1986 to January 1996 were identified. INTERVENTIONS: Warfarin was used after surgery by 72% of patients and aspirin was used by the remainder of them. MAIN OUTCOME MEASURES: Life table primary patency and limb salvage rates were compared for sex, diabetes mellitus status, location of distal prosthetic anastomosis (above knee vs. below knee), and anticoagulation drug therapy (warfarin sodium vs aspirin) with log-rank statistics. RESULTS: Primary patency of CSB was 56% at 24 months, 29% at 48 months, and 20% at 84 months (SE <10%; mean follow-up, 19.6 months [range, 1.0-110.0 months]). Limb salvage rates were 64% at 24 months, 30% at 48 months, and 23% at 84 months (SE <10%); 66% and 90% of patients had failed grafts requiring amputation by 3 months and 1 year, respectively. CONCLUSIONS: Composite sequential bypass for limb salvage provides reasonable 2-year patency. However, patency rates steadily declined from year 2 to year 5. After CSB failure, limb salvage rates are poor, with 90% of patients progressing to amputation within 1 year.