Mechanism of increased collateral airway resistance during inhomogeneous inflation of excised dog lungs

Collateral airway resistance was measured during inflation of an excised lung lobe or a segment within the lobe. Gas blown into the outer lumen of a double lumen catheter (Vcoll) inflated the segment and exited via collateral airways. Pressure at the catheter tip (Pct) was measured through the inner lumen of the catheter, and transpulmonary pressure (Pao) was measured at the lobar bronchus. A pleural capsule measured pressure in the segmental subpleural alveoli (Ps). The segment was inflated with helium (He), air, or sulfurhexafluoride; the lobe was ventilated with air. Collateral airway resistance [Rcoll = (Pct-Pao)/Vcoll], intrasegmental airway resistance [Rs = (Pct-Ps)/Vcoll], and resistance of airways passing through the segment-lobar interface [Ri = (Ps-Pao)/Vcoll] were calculated. Rcoll, Rs, and Ri were decreased by lobar inflation and increased by segment inflation. The latter increase was due to nonlaminar flow in intrasegmental airways. The major resistance was Ri when Vcoll was laminar or transitional. Moody plots suggested that lobar inflation caused intrasegmental airway dilation whereas segment inflation did not affect segment airway geometry.     

Generation and characterization of a human monoclonal antibody that neutralizes diverse HIV-1 isolates in vitro.

OBJECTIVE: The purpose of this study was to develop and characterize human monoclonal antibodies (HuMAb) that neutralize HIV-1. DESIGN: Based upon previous studies involving the generation of HuMAb that neutralize other enveloped viruses, we thought it feasible to generate HuMAb that might neutralize HIV-1. METHODS: A HuMAb was generated by fusing splenic B-cells from an HIV-positive patient with a mouse myeloma cell line. Flow cytometry was used to determine surface reactivity of the HuMAb on HIV-infected and non-infected cells. Radioimmunoprecipitation was employed to elucidate the antigen recognized by the HuMAb. A cell survival assay was used to determine the ability of the HuMAb to neutralize divergent isolates of HIV-1 in the presence or absence of complement. A gp120-CD4 inhibition enzyme-linked immunosorbent assay (ELISA) was developed in order to initiate studies to determine the mechanism of neutralization by the HuMAb. RESULTS: An anti-HIV HuMAb was generated that neutralized two HIV-1 isolates (IIIB and MN) without complement and which neutralized one divergent isolate (RF) and one clinical isolate in the presence of complement. This HuMAb, designated S1-1, was found, by flow cytometric analysis, to react with the surface of HIV-1-infected but not with uninfected cells. Radioimmunoprecipitation analysis demonstrated that S1-1 binds to native HIV gp120, but not dithiothreitol (DTT)-treated gp120. In addition, HuMAb S1-1 did not bind to denatured HIV antigens in Western blot analysis. HuMAb S1-1 effectively inhibited the binding of gp120 to soluble CD4 in ELISA. CONCLUSIONS: These results suggest that the epitope recognized by S1-1 is conformational and conserved among diverse HIV-1 isolates and may represent an uncharacterized HIV neutralizing domain within or close to the CD4 binding domain on gp120. HuMAb S1-1 might have a role to play in vaccine development or passive immunotherapy.     

Fetal heart rate response to milk predicts expression of the stretch response.

On the day before birth, rat fetuses respond to an intraoral infusion of milk with a stretch response that resembles the behavior of suckling pups at the nipple. Unlike the postnatal response, which occurs coincident with milk ejection, the fetal stretch occurs 3-5 min after milk infusion. Measurement of fetal heart rate (HR) is useful as a predictor of the fetal stretch response. Expression of the stretch response was preceded by a reduction in HR variability and a transient episode of bradycardia. Fetuses that did not stretch showed a delayed reduction in HR variability and no evidence of HR deceleration. Systematic changes in fetal HR may be indicative of changes in fetal state associated with milk infusion and the stretch response.     

The effect of cocaine on hippocampal cholinergic and noradrenergic metabolism

Rats treated with L-cocaine HCl exhibited an increase in hippocampal acetylcholine turnover, as measured by a mass fragmentographic technique. Furthermore, the ratio of hippocampal 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine increased significantly. Possible mechanisms of the increased cholinergic activity are discussed.     

Rising mortality from motor neurone disease in Sweden 1961–1990: the relative role of increased population life expectancy and environmental factors

Recent studies of mortality from motor neurone disease (MND) in Sweden have demonstrated rising levels of mortality from the disease, especially amongst older age groups. Case-control investigations have suggested that certain environmental factors are significantly related to variations in mortality from the disease, and are associated with a probable individual susceptibility to MND. This study applies an innovative epidemiological technique to longitudinal and cohort analysis of Swedish mortality from MND during the period 1961 to 1990. Survival modelling shows that a subpopulation susceptible to MND exists in Sweden, as has been demonstrated in other countries. The increased life expectancy of the Swedish population since 1961 has resulted in more of that susceptible population living to the ages at which MND is expressed, explaining the majority of the increase in mortality from the disease. However, environmental factors may play a role in accelerating the course of MND and may affect the timing of death within the susceptible sub-population.     

Dynamic and steady-state ventilatory and gas exchange responses to arm exercise.

Previous studies have suggested that, for the same power output, arm exercise requires higher oxygen uptake (VO2), carbon dioxide output (VCO2), and ventilation (VE) than leg exercise and that response kinetics are slower. To evaluate these differences, four healthy subjects performed a total of 95 arm cranking tests. Each subject performed several tests at each of three or four power outputs spaced evenly below the maximum the subject could sustain (average = 53 W). Breath-by-breath responses to identical stimuli were averaged. End-exercise blood lactate was determined at each power output. Responses were compared to leg exercise responses in these subjects (J. Appl. Physiol. 67:547-555, 1989). For power outputs unassociated with lactic acidosis, differences between steady-state VO2, VCO2, and VE responses for arm and leg exercise were not significant. At higher power outputs, the higher VO2, VCO2, and VE during arm exercise were well correlated with higher lactate. For power outputs not engendering lactic acidosis, the time constants (tau) for VO2, VCO2 and VE were not greatly different for arm than for leg exercise. For each variable, at higher power outputs tau became longer by an amount correlated with higher lactate level. Like leg exercise, the slower kinetics of VO2 and VE (but not VCO2) at higher power outputs were well described as a superimposed slower component. We conclude that both dynamic and steady-state responses of VE and gas exchange to arm exercise do not differ substantially from those to leg exercise so long as the power output does not elevate blood lactate.     

Anulus fibrosus in bulging intervertebral disks

In this investigation the association of radial tears of the anulus fibrosus and bulging of the intervertebral disk was studied. An index of disk bulging was measured in sagittal anatomic sections in 149 lumbar disks from 31 cadavers. The indexes of disk bulging were correlated with stages of disk development and the presence of an annular tear. The largest disk-bulging indexes were always associated with radial tears of the anulus. Eighty-four percent of the disks with radial tears had disk-bulging indexes greater than 2.5 mm. Most normal adult disks had an index of less than 2.5 mm. The results challenge the concept that the anulus fibrosus is intact in bulging disks, although ruptured in herniated disks.