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Biomedical subjects

J G King

Publications and source records attributed to J G King.

18 recordsLinked to original sources

Time responses of cancellous and cortical bones to sciatic neurectomy in growing female rats.

Effects of unilateral sciatic neurectomy on the responses of both cancellous and cortical bones were studied in growing female rats at 0, 1, 4, 8, and 12 weeks after operation. Using double-fluorescent labeling techniques, histomorphometric analyses were performed on longitudinal sections of proximal tibial metaphyseal secondary spongiosa (PTM) and on cross sections of tibial shaft (TX). In PTM, sciatic neurectomy not only inhibited the age-related bone gain, but also reduced the trabecular bone mass by 46%, which was accompanied by decreases in trabecular number, thickness, and node to node density, and an increase in trabecular separation and free end to free end density. The bone loss occurred mainly between 1 and 4 weeks after operation. A sharp increase in bone formation indices was observed during the first week after nerve section. However, these endpoints quickly dropped to levels lower than those of sham-operated controls at 4 weeks, and were not different from the control levels at 8 weeks after operation. Eroded surface increased progressively after sciatic neurectomy during the 12 weeks experimental period. In TX, sciatic neurectomy inhibited the age-related increase in total tissue area that maintained it at the basal control level. However, the cortical bone area in neurectomized legs was lower than that in sham-operated controls. Sciatic neurectomy also stimulated the bone formation indices on both periosteal and endocortical surfaces during the first week after operation. These endpoints declined sharply between 1 and 4 weeks and then maintained at control levels between 8 and 12 weeks post surgery. Endocortical eroded surface increased 1 week after neurectomy, reached the peak at 8 weeks, and then decreased thereafter. These findings suggest that (1) sciatic neurectomy not only inhibited age-related bone gain but also induced marked bone loss in cancellous bone site and inhibited age-related bone gain in cortical bone site, which mainly resulted from the decrease in bone formation and the increase in bone resorption; (2) the changes in both cancellous and cortical bones responded to sciatic neurectomy occurred mostly within the first 4 weeks and stabilized between 8 and 12 weeks after surgical intervention. In conclusion, the unilateral sciatic neurectomized rat is a complex model in which to study osteopenia. Despite sciatic neurectomy being a simple operation, the interactions of skeletal responses to postsurgical regional acceleratory phenomenon (RAP) and disuse and adaptation changes cannot be clearly differentiated. Furthermore, the complications from growth and aging should be avoided.

Animals

Endogenous natriuretic factors 3: isolation and characterization of human natriuretic factors LLU-alpha, LLU-beta 1, and LLU-gamma.

A low molecular weight endogenous substance believed to be responsible for extracellular fluid homeostasis in mammals has been sought for many years. Our goal is to isolate and structurally characterize this putative "natriuretic hormone." We have developed an assay using the conscious rat to measure prolonged natriuresis (Benaksas et al (1993) Life Sciences, 52, 1045-1054), the activity originally described for this putative substance. Using this assay we have identified a number of natriuretic compounds isolated from human uremic urine. The collected urine is processed by ultrafiltration (< or = 3 kDa), gel filtration chromatography (G-25) and extraction with isopropanol and diethyl ether. The organic soluble material is then subjected to sequential high-performance liquid chromatography. We report here the initial characterization of two pure isolates (LLU-alpha and LLU-gamma) obtained by this method, and the structural elucidation of a third pure compound, LLU-beta 1, a natriuretic and previously unreported metabolite of the drug diltiazem.

Animals

Abnormalities of the breast caused by biopsy: spectrum of mammographic findings.

It is important for radiologists to be familiar with the spectrum of mammographic abnormalities caused by postbiopsy changes in the breast. Although many breast biopsies leave no residual abnormality, occasionally an atypical manifestation of a biopsy scar may produce a radiologic finding suspicious enough to mandate a biopsy. Problem-solving maneuvers recommended to increase confidence that a change is related to a recent biopsy include (1) skin markers; (2) comparison with preoperative films; (3) correlation with physical examination; (4) tailored mammographic views, including focal spot compression, magnification, and tangential views; and (5) postoperative and follow-up mammograms.

Biopsy, Needle

Determination of normal transverse mediastinal width and mediastinal-width to chest-width (M/C) ratio in control subjects: implications for subjects with aortic or brachiocephalic arterial injury.

We measured transverse mediastinal width and mediastinal-width to chest-width (M/C) ratio on supine films of 100 nontraumatized controls. In 95% the transverse mediastinal width was less than 7.5 cm and the M/C ratio was less than 0.38. Thus a transverse width of 7.5 cm or more or an M/C ratio of 0.38 or more can be defined as abnormal with 95% confidence. Application of these values to determine abnormality in 32 patients with proven aortic or brachiocephalic injury showed that the transverse mediastinal width was within normal limits in 41% and M/C ratio was normal in 69%. Utilizing smaller values that would identify all abnormals resulted in false positive rates in the controls of 74% and 87%, respectively. However, one or more of eight specific signs of mediastinal abnormality related to hemorrhage or pseudoaneurysm formation were present in 94% of abnormals compared to only 11% of controls. Because of extreme overlap of transverse mediastinal width and M/C ratio between normals and abnormals, precise measurement of the mediastinum cannot reliably separate the two groups. The subjective assessment of anatomic mediastinal abnormality remains a superior plain film method in determining the need for aortography.

Adolescent

The potential effects of radiographic criteria to exclude aortography in patients with blunt chest trauma. Results of a study of 32 patients with proved aortic or brachiocephalic arterial injury.

The purpose of this study was to test the effectiveness, in patients with known aortic or brachiocephalic arterial injury, of five previously published radiographic criteria for excluding aortography in patients with blunt chest trauma. These criteria were (1) normal findings on erect chest radiograph; (2) normal aortic arch and left subclavian artery; (3) normal aortic arch, descending aorta, aortopulmonary window, tracheal position, and left paraspinal interface; (4) normal right paratracheal stripe and nasogastric tube position, and (5) normal aortic arch and tracheal and nasogastric tube position. One or more of these criteria were met in 6% to 25% of patient with major thoracic arterial injury, depending on the criteria used. Interestingly, two (6%) patients had radiographs that showed no specific signs of mediastinal hemorrhage, which indicates that the chest radiograph is limited in its sensitivity to detect major thoracic arterial injury. Because of these results, we do not believe that attempts to limit aortography in patients with supine film evidence of mediastinal abnormality, based on the absence of certain signs of mediastinal hemorrhage, are warranted. Furthermore, an abnormal radiograph cannot be relied on as the sole criterion for aortography if the goal of care is to detect as close to 100% of vascular injuries as possible.

Aorta, Thoracic

A scanning micropipette molecule microscope.

A movable quartz micropipette, whose tip is sealed with a polymer plug, is used as a liquid-vacuum interface to a mass spectrometer. A light microscope allows observation of, and positioning of, the micropipette tip on the surface of a sample mounted in a perfusion chamber. This forms the basis of an instrument which enables one to study, in vitro, the localization of transepithelial transport of water and other molecules. Some preliminary results from the use of this instrument are presented.

Animals

Time course of active Na transport and oxidative metabolism following transepithelial potential perturbation in toad urinary bladder.

The use of an Ussing chamber with well-defined mixing characteristics coupled to a mass spectrometer permits the concurrent evaluation of transepithelial current and oxidative metabolism with improved temporal resolution. The time-course of the amiloride-sensitive current Ia and the rate of suprabasal CO2 production JsbCO2 were observed in 10 toad urinary bladders at short-circuit and after clamping delta psi at 100 mV, serosa positive. Following perturbation of delta psi (0 leads to 100 mV), Ia declined sharply within 1/2 min, remaining near constant approximately 15 min, and then increased slightly. JsbCO2 declined more gradually, remained near constant at approximately 4-7 min, and then declined further. Detailed analysis revealed an early quasi-steady state with near constancy of JsbCO2 starting at 2.9 +/- 1.1 (SD) min and lasting 4.7 +/- 1.8 (SD) min, followed by relaxation to a later steady state at about 15 min. During the early quasi-steady state, Ia was also nearly constant. Considering that in steady states Ia/F approximately or equal to JaNa, the rate of transepithelial active Na transport, during the early quasi-steady state mean values +/- SE of JaNa, JsbCO2 and (JaNa/JsbCO2) were, respectively, 29.9 +/- 1.7%, 59.4 +/- 3.2%, and 56.4 +/- 5.7% of values at short-circuit. Corresponding values during the late steady state were 41.4 +/- 6.0%, 38.2 +/- 6.1%, and 111.3 +/- 8.6%. Thus the flow ratio JaNa/JsbCO2 was depressed significantly during the early quasi-steady state, but returned later to the original value. The results of measurements of Ia and JsbO2 in three hemibladders were qualitatively similar. In terms of a phenomenological "black-box" treatment the findings are consistent with earlier studies indicating incomplete coupling between transport and metabolism. Further studies will be required to clarify the molecular basis for these observations.

Adenosine Diphosphate

A mass spectrometer to measure transepithelial unidirectional labeled water fluxes.

A sealed quartz micropipette forms a liquid-vacuum interface that together with a uranium reduction element and a mass spectrometer functions as an in vitro real-time labeled water-selective microelectrode. Its performance is demonstrated by monitoring unidirectional fluxes across toad urinary bladder. This instrument has direct applicability to studies of water flux across epithelial membranes and could also be useful in monitoring water fluxes across such preparations as isolated tubules or capillaries.

Animals

Use of mass spectrometer to measure CO2 and O2 fluxes in voltage-clamped epithelia.

A quadrupole mass spectrometer was coupled to an Ussing chamber in order to evaluate rates of oxidative metabolism in voltage-clamped epithelia. Well-defined mixing characteristics of the continuously perfused chamber allowed CO2 and O2 concentrations to be related to rates of CO2 efflux, JCO2, and oxygen influx, JO2. The use of a model tissue to simulate step changes in JCO2 validated the treatment, with response within a minute. Monitoring of metabolism was facilitated by use of a desk-top computer, which evaluated JCO2 at 6-s intervals. Concurrent measurements of electrical current and JCO2 were made in the toad urinary bladder in order to relate active sodium transport to metabolism; the use of amiloride to eliminate active transport and the associated metabolism then allowed evaluation of the rates of active Na transport (JNa) and suprabasal metabolism (JsbCO2), and their ratio JNa/JsbCO2. We report the ability to resolve a 5 pmol/s change in CO2 efflux or an 11 pmol/s change in O2 influx rates.

Animals

The molecule microscope: a new instrument for biological and biomedical research.

We describe a new instrument, the molecule microscope, which reveals directly spatial variations in the rate of evaporation of molecules from surfaces by using neutral molecules instead of light or charged particles used in existing kinds of microscopes. The surface composition of the sample determines the binding energy of the evaporating molecules and, hence, the rate of evaporation, which also depends on permeability of the sample when the molecules come either from within or from the other side. We show first results obtained with our apparatus, discuss the design of an instrument now under construction with approximately 1-mum resolution, and describe briefly some more advanced versions under consideration with approximately 100-A resolution.

Animals