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.     

Human immunodeficiency virus infection in disadvantaged adolescents. Findings from the US Job Corps

OBJECTIVE--To describe the human immunodeficiency virus (HIV) epidemic among socially and educationally disadvantaged young persons in the United States. DESIGN.-We analyzed demographic and geographic findings from the screening of Job Corps students for antibody to HIV. SETTING--The Job Corps is a federal training program for disadvantaged, out-of-school youth. POPULATION SCREENED--Residential students aged 16 to 21 years who entered the Job Corps from October 1987 through February 1990. MAIN OUTCOME MEASURE--Rates of observed HIV infection in entering students, stratified by demographic and geographic features. RESULTS--Of 137,209 Job Corps students screened, 488 were HIV seropositive (3.6 per 1000), a seroprevalence rate higher than that among military applicants of the same age. Overall seroprevalence was slightly higher in male (3.7 per 1000) than in female (3.2 per 1000) Job Corps students, but among those students aged 16 and 17 years, seroprevalence was higher among females (2.3 per 1000) than among males (1.5 per 1000) (P less than .05). For students aged 16 to 21 years, seroprevalence increased with year of age: 1.8 per 1000 per year for males and 0.7 per 1000 per year for females. Among those aged 21 years, HIV prevalence was 8.9 per 1000. For black and Hispanic students from large Northeastern cities, seroprevalence increased by 4.3 per 1000 per year of age and reached 24.8 per 1000 (one of 40) in students aged 21 years. However, among students from rural areas and small towns, HIV seroprevalence was disproportionately high in the Southeast. Compared with recently described US patients with the acquired immunodeficiency syndrome, HIV-infected students who entered the Job Corps were much more likely to be female. CONCLUSIONS--These findings show that disadvantaged, out-of-school adolescents are at high risk for HIV infection. The screening results identified surprisingly high seroprevalence in the southeastern United States and demonstrated a marked shift in the HIV epidemic to young women. Controlling the HIV epidemic among teenagers must include interventions that will reach adolescents early and outside of the formal educational system.     

Blood flow acceleration in the carotid and brachial arteries of healthy volunteers: respective contributions of cardiac performance and local resistance

Summary— The influence of local resistance and cardiac performance on peripheral blood acceleration was investigated in 14 healthy male volunteers. Steady and pulsatile flow was studied in the brachial and in the common carotid arteries, ie, two territories that exhibit marked differences in resistive characteristics. Instantaneous blood velocity (V), mean blood velocity (V_m) and artery diameter (D) were evaluated at rest by an ultrasonic range-gated pulsed Doppler flowmeter using a double transducer probe, thus allowing the calculation of mean blood flow (Q). Mean local resistance (R) was obtained by dividing the mean arterial pressure by Q. The peak value of the local acceleration of the blood was obtained by computer-assisted calculation of the first derivative of instantaneous blood velocity (G_max = +dV/dt_max). Peak aortic blood acceleration (GAo) was simultaneously measured from the suprasternal notch using a pulsed Doppler velocity meter. In the brachial and the common carotid arteries, G_max was of a similar magnitude (551 ±30 and 555 ± 44 cm/s², respectively) despite major differences in the respective D, V_m, Q and R values. In neither artery was there a relationship between G_max and either resting Q or R. At the brachial artery level, G_max was positively related to GAo ( r = 0.79, P = 0.0008). At the common carotid artery level, there was a weak, although non significant relationship between G_max and GAo ( P = 0.08). Our results indicate that the local acceleration of peripheral blood flow in the brachial artery is related rather to upstream central impulse than to downstream hemodynamics, and suggest some regional differences in the hemodynamic determinants of the local acceleration of peripheral blood flow.     

Monitoring left ventricular dilation in mice with PET.

Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.