Biomedical subjects
Publications and source records attributed to M R Zamora.
Herein we report Lactobacillus pneumonia in a lung transplant recipient. The organism may have been normal flora in the donor but was a pathogen in the immunosuppressed recipient. Antibiotic therapy should include penicillin or clindamycin.
To investigate the role of endothelin-1 (ET-1) in the pathogenesis of hypoxic pulmonary hypertension, we studied the effects of a recently described endothelin-receptor antagonist (ETA), BQ123, on the development of this process. Intraperitoneal osmotic pumps were placed into 8-wk-old Sprague-Dawley rats that received either saline or BQ123 (0.15 mg/h). The rats were maintained in room air normoxia or placed in a hypobaric chamber (380 Torr) for 2 wk to induce hypoxic pulmonary hypertension. There were no hemodynamic differences between normoxic rats treated with either saline or BQ123. However, treatment with BQ123 attenuated the hypoxia-induced increase in pulmonary arterial mean pressure and total pulmonary resistance index by 60 and 87% respectively. There was also a reduction in hypoxia-induced right ventricular hypertrophy in the BQ123 group. Histological studies performed using a barium-gelatin fixation technique in hypoxic BQ123-treated animals demonstrated a decrease in medial wall thickness in arteries corresponding to the respiratory and terminal bronchioles, respectively. Similarly, there was a significant reduction in the degree of muscularization of more distal vessels at the level of alveolar ducts in BQ123-treated hypoxic rats. We conclude that the ETA-receptor antagonist BQ123 attenuates the development of hypoxic pulmonary hypertension in rats in vivo, thereby suggesting a possible contributing role for ET-1 and the ETA receptor in the pathogenesis of this process.
Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor that was recently shown to exhibit bronchoconstrictive properties in vitro. In asthmatic patients, the expression of ET-1 peptide was also shown to be increased in endobronchial biopsies. Thus, we postulated that ET-1 could be higher in subjects with nocturnal asthma. Bronchoalveolar lavage (BAL) fluid levels of ET-1 were measured in 10 subjects with nocturnal asthma and 6 normal volunteers at 0400 h (nighttime groups) and in an additional 7 subjects with nocturnal asthma and 6 control subjects at 1600 h (daytime groups). ET-1 levels were significantly lower in the nighttime asthmatic group (median 39.3 pg/mg protein, 7.3 to 44.0 IQ) than in the nighttime control group (median 77.4 pg/mg protein, 46.8 to 121.9 IQ; p = 0.01) or the daytime asthmatic group (median 56.8 pg/mg protein, 51.6 to 97.4 IQ; p = 0.04). ET-1 levels did not differ significantly between the daytime asthmatic and the daytime control groups or between control groups. Additionally, the overnight reduction in lung function was significantly correlated with lower BAL ET-1 levels (r = 0.57, p = 0.05). These results suggest that ET-1 plays a role in the overnight worsening of asthma and perhaps is more tightly tissue bound, resulting in lower levels of BAL fluid.
We describe a patient with type 3-C polyglandular autoimmune syndrome who presented with diffuse alveolar hemorrhage and normal renal function. The diagnosis of antibasement membrane antibody disease was established by immunofluorescent staining of transbronchial biopsy specimens. We suggest the incorporation of antibasement membrane antibody disease into the spectrum of diseases that define the polyglandular autoimmune syndromes.
Our data suggest that CMVIG in combination with ganciclovir effectively reduces the incidence, and delays the onset of CMV infections in seropositive lung transplant recipients. In addition, its use may be associated with less severe CMV infection and a lower incidence of bacterial or fungal opportunistic infection. Although the number of patients in the study is small, high-titer CMVIG may be more effective than standard titer immunoglobulin in the prevention of CMV disease in lung transplant recipients. Several questions remain in addition to these: What is the optimal dosage and duration of treatment with CMVIG for prophylaxis of CMV infection and disease in lung transplant recipients; Is this strategy cost-effective; Will it reduce the incidence of obliterative bronchiolitis following lung transplantation and enhance allograft survival? A prospective, random-assignment trial is warranted to answer these questions.
Endothelin-1 (ET-1) is a potent endogenous vasoactive peptide whose role in regulation of vascular tone is unclear. BQ123 is a recently described ETA receptor antagonist which may be useful in further investigation of the physiologic and pathophysiologic significance of ET-1. To test its efficacy in the pulmonary circulation, the vascular response to exogenous ET-1 with and without BQ123 was assessed in rat pulmonary artery (PA) rings and salt-perfused lungs. In both main and distal (250-350 microns ID) PA rings, BQ123 significantly attenuated ET-1-induced contractility, but was more effective in the larger vessels. Likewise, BQ123 significantly blunted ET-1-induced vasoconstriction in perfused lungs by > 80%. In addition, it had no effect on ET-3-mediated or U46619-mediated vasoconstriction, nor did it influence ET-1-induced vasodilation. Development of ET-1-associated hydrostatic edema was also unaffected by BQ123. We conclude that BQ123 effectively attenuates ET-1-induced vasoconstriction in both PA rings and in isolated perfused lungs. The absence of effect of BQ123 on ET-3 vasoconstriction, ET-1 vasodilation, or ET-1- and ET-3-induced hydrostatic edema formation suggests that these processes may be transduced through a non-ETA receptor.
The human epidermal-melanin unit exists as a complex interplay of cell-cell interactions. Melanocytes synthesize melanin and transfer it to the surrounding keratinocytes, which, in turn, produce factors that affect melanocyte homeostasis, growth, and melanization. Endothelin-1 (ET-1), a vasoconstrictor peptide produced by endothelial cells, has recently been shown to stimulate human melanocyte proliferation and tyrosinase activity. To investigate the possibility that keratinocytes synthesize and secrete ET-1, we grew human keratinocytes in a defined serum-free medium and measured ET-1 levels in the keratinocytes and the keratinocyte-conditioned medium. Northern analysis of keratinocyte total RNA also was performed. We found that human keratinocytes express preproET-1 mRNA and translate the message to ET-1 protein, which is secreted into the keratinocyte medium. Human keratinocytes produced ET-1 in a time-dependent manner with total production of 20.1 +/- 1.1 pg ET-1/10(6) cells at 24 h (n = 7). Although total ET-1 production (secreted plus cell-associated ET-1) was similar, the proportion of secreted versus cell-associated ET-1 varied widely among the different donors. We have found that human keratinocytes synthesize and secrete ET-1 in vitro. From these data we believe that the keratinocyte could be an in vivo epidermal source of this melanocyte growth and pigmentation factor.
Endothelin-1 (ET-1) is a potent vasoactive peptide that has been reported to cause lung edema. This study tested if the edemagenic effect of ET-1 is due to preferential venoconstriction and, if so, whether the site of resistance is similar with salt solution (PSS) and more physiologic blood perfusate. ET-1 caused concentration-dependent contraction of pulmonary arterial and venous rings, with an EC50 of 1.3 nM in artery and 0.6 nM in vein (p less than 0.05). In PSS-perfused lungs, 5 nM ET-1 caused a 7.0 +/- 0.8 torr pressor response that was associated with a 5.0 +/- 0.3 torr increase in microvascular pressure and a 530 +/- 20 mg increase in lung weight within 10 min. In contrast, KCl-treated lungs had an equivalent pressor response (7.4 +/- 1.1 torr), yet the microvascular pressure increased by only 2.5 +/- 0.4 torr (p less than 0.05 from ET-1) and the lung weight was unchanged. Meclofenamate did not prevent the effect of ET-1 on microvascular pressure or lung weight. In blood-perfused lungs, ET-1 caused a 7.3 +/- 0.1 torr pressor response but only a 2.0 +/- 0.5 torr increase in microvascular pressure and no increase in lung weight. ET-1 had no effect on permeability either of cultured endothelial cell monolayers or in the pulmonary microvasculature in vivo. We conclude that the edemagenic effect of ET-1 in PSS-perfused lungs is mediated through venoconstriction and an increase in microvascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine whether the vasoconstriction in Raynaud's phenomenon is associated with raised concentrations of the endothelium-derived vasoconstrictor endothelin (ET-1), responses to cold pressor testing were examined in 7 subjects with primary Raynaud's phenomenon and in 7 control subjects. Baseline serum ET-1 levels (pg/ml), as measured by radioimmunoassay, were three times higher in Raynaud's subjects (5.3 [SEM 1.7] pg/ml) than in controls (1.7 [0.3]). With progressive local cooling digital arterial pulsatility, as measured by plethysmography, fell earlier and to a greater extent in Raynaud's subjects than in controls, with a half-maximum decrement in pulsatility occurring at 27 [2.6] degrees C and 18 [0.5] degrees C, respectively. Temperature reduction sufficient to cause loss of pulsatility in the Raynaud's subjects produced increases in ET-1 concentrations in both groups that were greater in Raynaud's (10.3 [4.4] pg/ml) than in control subjects (2.7 [0.9] pg/ml). Serum ET-1 in the contralateral arm rose in parallel to but to a lesser extent than that in the cold-challenged arm. Increases in ET-1 concentrations were temporally related to loss of pulsatility but followed the onset of symptoms. Thus the increased basal and stimulated serum endothelin concentrations in Raynaud's disease are associated with the enhanced, prolonged vasospasm of this disorder.