Recent Publications by CFE Educators

Although there is considerable evidence that primary afferent-derived substance P contributes to the transmission of nociceptive messages at the spinal cord level, the population of neurons that expresses the substance P receptor, and thus are likely to respond to substance P, has not been completely characterized. To address this question, we used an antibody directed against the C-terminal portion of the rat substance P receptor to examine the cellular distribution of the receptor in spinal cord neurons. In a previous study, we reported that the substance P receptor decorates almost the entire dendritic and somatic surface of a subpopulation of spinal cord neurons. In the present study we have taken advantage of this labeling pattern to identify morphologically distinct subpopulations of substance P receptor-immunoreactive neurons throughout the rostral-caudal extent of the spinal cord. We observed a dense population of fusiform substance P receptor-immunoreactive neurons in lamina I at all segmental levels. Despite having the highest concentration of substance P terminals, the substantia gelatinosa (lamina II) contained almost no substance P receptor-immunoreactive neurons. Several distinct populations of substance P receptor-immunoreactive neurons were located in laminae III-V; many of these had a large, dorsally directed dendritic arbor that traversed the substantia gelatinosa to reach the marginal layer. Extensive labeling was also found in neurons of the intermediolateral cell column. In the ventral horn, we found that labeling was associated with clusters of motoneurons, notably those in Onuf's nucleus in the sacral spinal cord. Finally, we found no evidence that primary afferent fibers express the substance P receptor. These results indicate that relatively few, but morphologically distinct, subclasses of spinal cord neurons express the substance P receptor. The majority, but not all, of these neurons are located in regions that contain neurons that respond to noxious stimulation.

This study was designed to test the hypothesis that pulmonary artery pressure at rest and during exercise differs between patients with a transplanted heart and normal subjects and to determine the mechanisms responsible for the difference. Twenty-one patients who had undergone heart transplantation 1.5 to 27 months earlier without current evidence of acute cardiac rejection and 25 normal subjects were studied by exercise Doppler echocardiography. Systolic pulmonary artery pressure was higher at baseline in heart transplant patients than in normal subjects, at 31.6 +/- 9 mm Hg (mean +/- SD) versus 22.5 +/- 4, respectively (p = 0.0001). The increase in systolic pulmonary artery pressure with exercise was 1.4 times higher in heart transplant patients and correlated with pretransplantation pulmonary vascular resistances (r = 0.55; p = 0.01). In contrast, cardiac index at baseline or during exercise did not differ between the two groups. Diastolic parameters and ejection fraction at baseline or during exercise did not correlate with systolic pulmonary artery pressure. In conclusion, Doppler exercise echocardiography offers an alternative, safe method hemodynamic study of the transplanted heart. Although an abnormal increase in left ventricular filling pressure with exercise has been well documented, further studies are needed to investigate and characterize potential abnormalities in pulmonary vascular tone in the transplanted heart.

We report on the surprising loss of transganglionic and retrograde labeling in the spinal cord of the rat after co-injection of the tracers wheat germ agglutinin-HRP (WGA-HRP) and choleragenoid toxin-HRP (CTB-HRP) into the sciatic nerve. Injection of WGA-HRP alone produced a pattern of transganglionic label consistent with transport by small-diameter primary afferent fibers. Small cell bodies were labeled in the ipsilateral dorsal root ganglion (DRG) and there was dense terminal labeling in the superficial dorsal horn of the lumbar spinal cord. Injection of CTB-HRP alone produced a pattern of transganglionic labeling consistent with transport by large-diameter primary afferent fibers. Large cell bodies were labeled in the DRG and there was dense terminal labeling in the nucleus proprius (Laminae III-V) in the spinal cord. CTB-HRP also produced extensive retrograde labeling of ventral horn motor neurons. When the two tracers were co-injected, we found few labeled cells in the ipsilateral DRG and there was almost complete loss of transganglionic terminal labeling in the lumbar spinal cord. Retrograde labeling of motor neurons was also significantly reduced. Even when one of the tracers (e.g., WGA-HRP) was injected 24 hr after and up to 10 mm proximal to the site of the first tracer (e.g., CTB-HRP), an inhibitory interaction was detected. The labeling pattern was always characteristic of the first tracer injected.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar macrophages (AM) play a key role in local immunoregulation. The objective of these studies was to compare the production of the pro- and mature forms of both interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) by AM from nine nonsmoking control subjects, six asymptomatic smokers, and nine patients with interstitial lung disease (ILD). IL-1 alpha and IL-1 beta steady-state mRNA levels in AM cultured over 20 h were determined using specific cDNA probes. IL-1 alpha, 35-kD pro-IL-1 beta, and 17-kD mature IL-1 beta protein levels in cell lysates and supernatants were determined by individual specific ELISAs. Before culture, the isolated AM contained no IL-1 alpha or IL-1 beta mRNA. AM from nonsmoking control subjects and asymptomatic smokers produced comparable levels of IL-1 alpha protein, 5.01 +/- 1.02 ng/ml and 4.54 +/- 1.07 ng/ml, respectively, only after stimulation with lipopolysaccharide (LPS) and not with granulocyte-macrophage colony-stimulating factor (GM-CSF). The majority of the IL-1 alpha was present in the cell lysates as 35-kD pro-IL-1 alpha, as determined by Western blot analysis. AM from patients with ILD produced higher levels of LPS-induced cell-associated IL-1 alpha protein (9.78 +/- 1.80 ng/ml, p = 0.031). LPS-induced IL-1 beta production by AM from nonsmoking control subjects (5.22 +/- 1.89 ng/ml) and asymptomatic smokers (4.39 +/- 0.66 ng/ml) was equivalent to total IL-1 alpha protein production.(ABSTRACT TRUNCATED AT 250 WORDS)

The early stage of idiopathic pulmonary fibrosis (IPF) is thought to involve a smaller number of alveoli and to be characterized predominantly by cellularity and minimal fibrosis, whereas advanced disease involves a large number of alveoli and is characterized predominantly by fibrosis with minimal cellularity. In addition, correlative studies have indicated that prognosis and response to therapy is determined in part by the extent of fibrosis and cellularity. This study was undertaken to determine whether pulmonary function assessment would help distinguish between the cellular and fibrotic phases of this disorder, as determined by a semiquantitative pathology scoring system that comprised four factor scores: fibrosis, cellularity, granulation/connective tissue, and desquamation. Ninety-six untreated patients with biopsy-confirmed IPF (27 never smokers, 32 current smokers, and 37 ex-smokers) were evaluated. In the group as a whole, there was no significant relationship between the fibrosis or the connective/granulation tissue factor scores and any of the physiologic parameters. The DLCO correlated with the "desquamation" and the total pathology scores, whereas the TLC and FVC correlated with the cellularity factor score. In the current smokers, the coefficient of elastic retraction, DLCO/VA, and FEV1/FVC ratio were significantly lower than in never smokers and ex-smokers, and TLC and FVC were higher than in never smokers. Also, the mean cellularity and granulation/connective tissue factor scores were significantly lower, and the desquamation factor score was significantly higher than those in never smokers and ex-smokers. Both age and smoking status were significant for the cellularity factor score, whereas for the connective/granulation tissue factor score, age was not significant but smoking status was.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on cultured cells have shown that agonists induce several types of G protein-coupled receptors to undergo internalization. We have investigated this phenomenon in rat striatum, using substance P (SP)-induced internalization of the SP receptor (SPR) as our model system. Within 1 min of a unilateral striatal injection of SP in the anesthetized rat, nearly 60% of the SPR-immunoreactive neurons within the injection zone display massive internalization of the SPR--i.e., 20-200 SPR+ endosomes per cell body. Within the dendrites the SPR undergoes a striking translocation from the plasma membrane to endosomes, and these dendrites also undergo a morphological reorganization, changing from a structure of rather uniform diameter to one characterized by large, swollen varicosities connected by thin fibers. In both cell bodies and dendrites the number of SPR+ endosomes returns to baseline within 60 min of SP injection. The number of neurons displaying substantial endosomal SPR internalization is dependent on the concentration of injected SP, and the SP-induced SPR internalization is inhibited by the nonpeptide neurokinin 1 receptor antagonist RP-67,580. These data demonstrate that in the central nervous system in vivo, SP induces a rapid and widespread SPR internalization in the cell bodies and dendrites and a structural reorganization of the dendrites. These results suggest that many of the observations that have been made on the internalization and recycling of G protein-coupled receptors in in vitro transfected cell systems are applicable to similar events that occur in the mammalian central nervous system in vivo.

The purpose of this study was to determine the prevalence and progression of pulmonary hypertension over a 5-year follow-up period in 28 patients with systemic lupus erythematosus (SLE) who were originally enrolled in an echocardiographic study of pulmonary hypertension in 1985 and 1986. Twenty healthy volunteers without cardiac or pulmonary disease participated as normal controls. Each patient and control underwent a complete Doppler echocardiographic study. Doppler echocardiographic recordings of tricuspid insufficiency, with saline contrast enhancement when necessary, were used to calculate pulmonary artery systolic pressure according to the modified Bernoulli equation. Doppler echocardiographic measurement of cardiac output was performed at rest for each subject, and pulmonary resistance was calculated by dividing the pulmonary artery systolic pressure by the cardiac output. These results were compared to results of the original studies to detect serial changes in pulmonary pressure and pulmonary resistance; results were also compared to the group of normal controls. The prevalence of pulmonary hypertension increased from 14% at the first study to 43% at follow-up. A significant increase in mean systolic pulmonary artery pressure was detected in the SLE patients during the follow-up period: 23.4 vs 27.5 mm Hg (p 0.005). In addition, a significantly higher pulmonary artery pressure was detected in the SLE patients compared with the normal controls (p 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)