Ex vivo identification of atherosclerotic plaque calcification by a 31P solid-state magnetic resonance imaging technique.

Calcified tissue is a common component of atherosclerotic plaques, and occurs most often in mature plaques. The process of calcification is a poorly understood risk factor that may contribute to a plaque's vulnerability to sudden rupture. In this study a solid-state imaging sequence, termed single-point imaging (SPI), was used to observe calcification directly in ex vivo atherosclerotic plaques. Standards were used to validate the ability of (31)P SPI to detect and differentiate calcification from crystalline cholesterol, phospholipids, and other plaque components. After suitable experimental parameters were found, human carotid specimens obtained by endarterectomy were imaged ex vivo by (31)P solid-state imaging and standard (1)H methods. In contrast to (1)H imaging methods, (31)P imaging detected only the calcification in the plaque.     

Cervical nerve root stimulation. Part I: technical aspects and normal data.

OBJECTIVE: Cervical nerve root stimulation (CRS) is a technique of assessing the proximal segments of motor axons destined to upper extremity muscles. Few studies report normal values. The objective was to determine CMAP onset-latencies and CMAP amplitude, area, and duration changes in healthy controls for the abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps, and riceps muscles. In addition, to determine the tolerability of CRS, as measured by the visual analog scale (VAS). METHODS: We studied 21 healthy volunteers prospectively with CRS using four target muscles (APB, ADM, biceps, and triceps) bilaterally. Collision studies were used in all APB recordings. VAS was obtained in all subjects. RESULTS: Mean CMAP onset-latencies were: APB 14 +/- 1.5 ms; ADM 14.2 +/- 1.5 ms; biceps 5.4 +/- 0.6 ms; triceps 5.4 +/- 1.0 ms. Onset-latency significantly correlated with height for all nerves. The mean change in CMAP amplitude and area (%) between most distal stimulation and CRS was: APB reduction of 15.1 +/- 11.6 and 4.9 +/- 3.6%; ADM reduction of 21.1 +/- 10.7 and 17.2 +/- 8.8; biceps reduction of 10 +/- 11.5 and reduction of 8.7 +/- 6.8; triceps increase of 3.3 +/- 5.2 and 11.0 +/- 9.9% respectively. Mean CMAP duration change between most distal stimulation and CRS was: APB, increase of 20.4 +/- 7.4%; ADM, increase of 14.4 +/- 8.5%; biceps, increase of 13.9 +/- 10.8%; triceps, increase of 7.7 +/- 6.7%. The mean VAS score was 3.8 +/- 1.2, and all subjects completed the study. CONCLUSIONS: The present study establishes normative data and indicates that CRS is a well-tolerated technique. SIGNIFICANCE: The normal values may be used as reference data for the needle CRS technique in the assessment of proximal conduction abnormalities.     

The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing

Wound healing involves a number of cellular and molecular events, many of which are controlled by soluble growth factors. In the process of healing, hepatocyte growth factor, a cytokine known to act as mitogen, motogen, and morphogen, has been postulated to play multiple roles during several stages of this complex biological process. Produced primarily by stromal fibroblasts, hepatocyte growth factor regulates angiogenesis, vascular permeability, cell migration, matrix deposition and degradation, and other biological processes. The current article discusses recent progress in understanding the multiple roles played by this growth factor in tissue repair.     

IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Angiodysplasia as the cause of massive lower gastrointestinal hemorrhage in a young adult

PURPOSE: This study was undertaken to clarify the importance of bleeding vascular ectasia of the colon as the etiology of massive lower gastrointestinal hemorrhage in patients 40 years of age or younger. METHODS: An otherwise healthy 21-year-old male was admitted to a tertiary medical center with massive lower gastrointestinal hemorrhage. Technetium-labeled red blood cell scan, selective visceral angiography, and colonoscopy identified the source of bleeding as vascular abnormality of the descending colon. Segmental colonic resection was performed. RESULTS: Histologic review of the specimen demonstrated a vascular ectasia. The patient recovered uneventfully and has had no further stigmata of hemorrhage. A review of the literature was undertaken to make clear the significance of vascular ectasia as the source for massive colonic hemorrhage in the young adult. CONCLUSION: This is the first report that documents histologically a vascular ectasia as the source of massive lower gastrointestinal hemorrhage in an otherwise healthy patient less than 40 years of age. Vascular ectasia is an uncommon cause of lower gastrointestinal hemorrhage in the young adult.The Chief, Bureau of Medicine and Surgery, Navy Department, Washington, DC, Clinical Investigation Program sponsored this report #84-16-1968-532, as required by HSETCINST 6000.41A. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.     

Membrane properties of an unusual intrinsically oscillating, wide-field teleost retinal amacrine cell

In the retina, amacrine cells modulate the transfer of information from bipolar to ganglion cells. The nature of the modulation depends on the synaptic input and the membrane properties of the cells. In the retina of white bass, we identified a class of bistratified, wide-field amacrine cell characterized by immunopositive labelling for GABA and calmodulin. In isolation, the cells presented resting membrane potentials averaging -69 mV although some cells settled at more depolarized values (-30 mV). Injection of depolarizing current pulses induced oscillatory membrane responses. When elicited from depolarized cells, the oscillations were short-lived (< 40 ms). For the most part, the oscillatory potentials of hyperpolarized cells remained unattenuated throughout the depolarizing pulse. The frequency of the oscillations increased logarithmically with mean membrane potential, ranging from 74 to 140 Hz. Cells exhibiting depolarized membrane potentials oscillated at twice that rate. When the membrane potential of these cells was hyperpolarized to -70 mV, the oscillations became unattenuated and slowed. We found the cells expressed voltage-gated sodium, potassium and calcium currents and calcium-dependent potassium currents. We demonstrate that the oscillatory potentials arose as a result of the interplay between calcium and potassium currents. The cells responded to local application of GABA and glycine, both of which modulate the oscillatory potentials. Glutamate and its analogues depolarized the cell and induced oscillatory potentials. Our results indicate that oscillatory responses of a type of wide-field amacrine cell are an intrinsic feature of the cell and not due to circuit properties.