Showing papers by "Veterans Health Administration published in 1984"
TL;DR: It is concluded that the measurement of TAPSE offers a simple echocardiographic parameter which reflects RVEF and is not dependent on either geometric assumptions or traceable endocardial edges.
970 citations
TL;DR: The present review will concentrate on only one aspect of the interaction between the immune and reproductive systems and involves interactions of pituitary hormones, gonadal steroid hormones and thymic hormones.
Abstract: Introduction IN THE PAST 10 years there has been a significant increase in studies relating to the function of the immune system. The recent popularity of research in this area is due in part to the awareness by the medical and scientific community of the importance of immune function in the maintenance of a disease-free homeostasis, to technological advances in the field of immunological research, and to the increased availability of funds for investigation in this area. From the rapidly expanding literature in this field it has become increasingly apparent that the immune system interacts with most, if not all, of the body systems. One of the most intriguing of these interrelationships is that which occurs between the immune and reproductive systems and involves interactions of pituitary hormones, gonadal steroid hormones and thymic hormones. Because of the complexity of this area the present review will concentrate on only one aspect of the interaction between the two systems, namely the effects of gon...
675 citations
TL;DR: Intraventricular injection of NPY was shown to markedly stimulate feeding and drinking during the illuminated period of the light/dark cycle, a time when rats ingest small amounts of food, and to represent one of the most potent stimulators of feeding yet to be described.
575 citations
TL;DR: The pattern of results suggests that the effect of aerobic exercise training was on central rather than on peripheral function, and it is speculated that aerobic exercise promoted increased cerebral metabolic activity with a resultant improvement in neuropsychological test scores.
560 citations
TL;DR: It is concluded that data sources for determining patient functional ability are not interchangeable and that patients may overstate their functional abilities, whereas significant others may understate them, relative to judgments of skilled nursing personnel.
Abstract: Measuring functional status using specific instruments is an important part of geriatric assessment. These instruments, however, often rely on data sources different from those with which they were originally validated. To study possible biasing effects of different data sources on functional status scores, we examined scores for two widely used instruments (the Lawton Personal Self-Maintenance Scale, PSMS, and Instrumental Activities of Daily Living, IADL, Scale) on a group of hospitalized elderly (n = 61) using three different data sources (the patients themselves, the patients' nurses, and significant others). Analysis showed that PSMS scores derived from patients were significantly higher than scores derived from significant others (p less than .025) and that patient-derived IADL scores were significantly higher than both nurse-derived scores (p less than .001) and significant-other-derived scores (p less than .001). We also compared scores for a group of nursing home patients (n = 68) on the Katz Activities of Daily Living (ADL) Scale, using data obtained from patients and their nurses. Again, the patient-derived scores were significantly higher than those from nurses (p less than .001). We conclude that data sources for determining patient functional ability are not interchangeable and that patients may overstate their functional abilities, whereas significant others may understate them, relative to judgments of skilled nursing personnel.
350 citations
TL;DR: The results suggest that warfarin, as a single anticoagulant agent, may favorably modify the course of some, but not all, types of human malignancy, among which is small cell carcinoma of the lung.
Abstract: VA Cooperative Study #75 was established to test in a controlled, randomized trial the hypothesis that warfarin anticoagulation would favorably affect the course of certain types of malignancy. No differences in survival were observed between warfarin-treated and control groups for advanced non-small cell lung, colorectal, head and neck and prostate cancers. However, warfarin therapy was associated with a significant prolongation in the time to first evidence of disease progression (P = 0.016) and a significant improvement in survival (P = 0.018) for patients with small cell carcinoma of the lung, including the subgroup of patients with disseminated disease at the time of randomization (P = 0.013). A trend toward improved survival with warfarin treatment was observed for the few patients admitted to this study with non-small cell lung cancer who had minimal disease at randomization. These results suggest that warfarin, as a single anticoagulant agent, may favorably modify the course of some, but not all, types of human malignancy, among which is small cell carcinoma of the lung. Further trials of warfarin may be indicated in patients with limited disease who have cell types that failed to respond when advanced disease was present.
321 citations
TL;DR: A fine structural analysis ofLewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis with posterior column and spinocerebellar tract involvement.
Abstract: Lewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis (ALS) with posterior column and spinocerebellar tract involvement. A fine structural analysis of these two structures has been performed in two brothers from a family ("C" family) previously described by Kurland and Mulder in 1955. The perikaryal hyaline inclusions consisted of accumulations of randomly oriented neurofilaments interspersed with thick linear densities associated with granular material. Some of the accumulations showed a central condensation. Cord-like, swollen neuronal processes were composed, for the most part, of numerous neurofilaments arranged parallel to the long axes. Dense structures were sometimes observed within the large bundles of filaments. They were composed of ill-defined dense, granular and fibrillar material associated with scattered vesicles and mitochondria. These dense areas were sometimes surrounded by various amounts of fine filaments, approximately 5 nm in diameter.
301 citations
TL;DR: The right hemisphere seems to be dominant for comprehending emotional prosody but not propositional prosody, and both LHD and RHD groups had more impaired comprehension of propositional Prosody than controls.
Abstract: We studied patients with damage of either the right (RHD) or left hemisphere (LHD) and control subjects to determine whether the RHD patients had a global or limited prosodic defect. Compared with LHD patients and controls, RHD subjects had decreased comprehension of emotional prosody. Both LHD and RHD groups had more impaired comprehension of propositional prosody than controls, but the RHD and LHD groups did not differ. The right hemisphere, therefore, seems to be dominant for comprehending emotional prosody but not propositional prosody.
269 citations
TL;DR: The 3 Å electron density map of a co-crystalline recognition complex between EcoRI endonuclease and the oligonucleotide TCGCGAATTCGCG reveals that a tight, complementary interface between the enzyme and the major groove of the DNA is the major determinant of sequence specificity.
Abstract: The 3 A electron density map of a co-crystalline recognition complex between EcoRI endonuclease and the oligonucleotide TCGCGAATTCGCG reveals that a tight, complementary interface between the enzyme and the major groove of the DNA is the major determinant of sequence specificity. The DNA contains a torsional kink and other departures from the B conformation which unwind the DNA and thereby widen the major groove in the recognition site.
258 citations
TL;DR: The hypothesis that nicotine from smoking can produce psychological changes that are independent of the state of nicotine withdrawal is supported.
236 citations
TL;DR: Clinical and pathologic findings suggest that lesions limited to the hippocampus can cause profound amnesia.
Abstract: A patient developed an amnesic syndrome after cardiopulmonary arrest Neuropathologic examination revealed pronounced anoxic injury to both hippocampi with little damage to other hemisphere structures The clinical and pathologic findings suggest that lesions limited to the hippocampus can cause profound amnesia
Journal Article•
TL;DR: The use of radiolabeled antibodies that are directed against tumor-associated antigens holds future promise as a new therapeutic approach to solid tumors that are resistant to conventional therapy.
Abstract: Antibodies which are directed against human tumor-associated antigens can potentially be used as carriers of radioactivity for in vivo diagnosis (radioimmunodetection) or treatment (radioimmunotherapy) of solid tumors, including colon, hepatoma, cholangiocarcinoma, and melanoma. Murine monoclonal antibodies (MOAB), produced by the hybridoma technique of Kohler and Milstein, are replacing conventional heterosera as sources of antibodies, because MOAB can be produced in large quantities as reproducible reagents with homogeneous binding properties. We have studied human melanoma using MOAB IgG and Fab fragments that recognize the human melanoma-associated antigens p97 and ''high-molecular-weight antigen''. Both antigens are found in the membrane of melanomas at much larger concentrations than in normal adult tissues. We have performed radioimmunodetection studies with whole immunoglobulin and have detected 88% of lesions greater than 1.5 cm. We have used Fab fragments for radioimmunotherapy and have found that large doses of radiolabeled antibodies (up to 342 mCi) can be repetitively given to patients without excessive end-organ toxicity. Two of three patients treated with high-dose radiolabeled antimelanoma Fab showed an effect from the treatment. Although both technical and biologic problems remain, the use of radiolabeled antibodies that are directed against tumor-associated antigens holds future promise as a new therapeutic approach to solidmore » tumors that are resistant to conventional therapy.« less
TL;DR: It is observed that naloxone reversed human fibroblast interferon mediated enhancement of human blood lymphocyte natural killer function, suggesting that circulating endogenous opioid peptides may have a physiologic role in regulating human bloodymphocyte natural killing.
TL;DR: The experiments reported here provide a possible molecular mechanism for theactivated macrophage cytotoxic effect and are significant that mitochondrial respiration and DNA replication, both strongly inhibited in target cells by activated macrophages, are metabolic pathways with enzymatic activity vulnerable to inhibition by depletion of intracellular iron.
TL;DR: A method is presented for determining the breakpoint of a line which suddenly changes slope at some unknown point and a statistical test is given for testing whether the broken line is a significantly better fit to the data than a single straight line.
TL;DR: The phonatory abnormalities noted in Parkinson's disease are related to rigidity in the phonatory posture of the larynx, correlated with the symmetry of trunk and limb Rigidity in 100% of the patients.
Abstract: Thirty-two unselected male patients with Parkinson's disease were examined by telescopic cinelaryngoscopy. Correlation of vocal abnormality and general neurologic symptoms with the laryngoscopic examination leads to the conclusion that the phonatory abnormalities noted in Parkinson's disease are related to rigidity in the phonatory posture of the larynx. The described dysfunctions correlated with the symmetry of trunk and limb rigidity in 100% of the patients.
Journal Article•
TL;DR: A review of the 118 primary aortoduodenal fistulas in the world's literature reveals that pain, palpable abdominal mass, and bleeding are inconsistently present as initial symptoms and that routine abdominal films, barium studies, and endoscopy have been ineffective as diagnostic aids.
TL;DR: Properties of the action potential and subthreshold response were studied in large layer V neurons in in vitro slices of cat sensorimotor cortex using intracellular recording and stimulation, application of agents that block active conductances, and a single-microelectrode voltage clamp.
Abstract: Properties of the action potential and subthreshold response were studied in large layer V neurons in in vitro slices of cat sensorimotor cortex using intracellular recording and stimulation, application of agents that block active conductances, and a single-microelectrode voltage clamp (SEVC). A variety of measured parameters, including action-potential duration, afterpotentials, input resistance, rheobase, and membrane time constant, were similar to the same parameters reported for large neurons from this region of cortex in vivo. Action-potential amplitudes and resting potentials were greater in vitro. Most measured parameters were distributed unimodally, suggesting that these parameters are similar in all large layer V neurons irrespective of their axonal termination. The voltage response to subthreshold constant-current pulses exhibited both time and voltage dependence in the great majority of cells. Current pulses in either the hyperpolarizing or subthreshold depolarizing direction cause the membrane potential to attain an early peak and then decay (sag) to a steady level. On termination of the pulse, the membrane response transiently overshoots resting potential. Plots of current-voltage relations demonstrate inward rectification during polarization on either side of resting potential. Subthreshold inward rectification in the depolarizing direction is abolished by tetrodotoxin (TTX). The ionic currents responsible for subthreshold rectification and sag were examined using the SEVC. Steady inward rectification in the depolarizing direction is caused by a persistent, subthreshold sodium current (INaP) (54). Sag observed in response to a depolarizing current pulse is due to activation of a slow outward current, which superimposes on and partially counters the persistent sodium current. Both sag in response to hyperpolarizing current pulses and rectification in the hyperpolarizing direction are caused by a slow inward "sag current" that is activated by hyperpolarizing voltage steps. The sag current is unaltered by TTX, tetraethylammonium, (TEA), Co2+, Ba2+, or 4-aminopyridine. Fast-rising, short-duration action potentials can be elicited by an intracellular current pulse or by orthodromic or antidromic stimulation. Spikes are blocked by TTX. The form of the afterpotential following a directly evoked spike varies among cells with similar resting potentials. Biphasic afterhyperpolarizations (AHPs) with fast and slow components were most frequently seen. About 30% of the cells displayed a depolarizing afterpotential (DAP), which was often followed by an AHP. Other cells displayed a purely monophasic AHP.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: A study of 43 help-seeking Vietnam veterans revealed that a reliable assessment of war trauma, the Combat Exposure Scale, could be constructed from dichotomous questions about seven stressful events, related significantly to current diagnosis of PTSD and intensity of symptoms.
Abstract: Although symptoms of Post-Traumatic Stress Disorder are expected to persist for many years, there is often no systematic assessment of Vietnam veterans' combat experiences. A study of 43 help-seeking Vietnam veterans revealed that a reliable assessment of war trauma, the Combat Exposure Scale, could be constructed from dichotomous questions about seven stressful events. Scale scores related significantly to current diagnosis of PTSD and intensity of symptoms. The Guttman scaling technique resulted in an ordering of events that provides clinically relevant information about the nature of trauma in the Vietnam War.
Journal Article•
TL;DR: The results indicate that chronic ingestion of ethanol decreased the fluidity and the ethanol sensitivity of the synaptic membranes of DBA/2 mice and suggest that chronic ethanol treatment also produced changes in the lipid arrangement or lipid-protein interactions of the intact membranes.
Abstract: DBA/2 mice were made tolerant to and dependent on ethanol by administration of an ethanol-containing liquid diet for 7 days. Fluorescent probe molecules were used to estimate the fluidity and ethanol sensitivity of brain synaptic membranes from these mice. The fluorescence polarization of cis- parinarate , trans- parinarate , and 1,6-diphenyl-1,3,5-hexatriene (probes of the membrane core) and 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene (a probe of the membrane surface) was higher in membranes from ethanol tolerant-dependent mice than in membranes from control mice. The decrease in fluorescence polarization produced by in vitro exposure to ethanol was attenuated in membranes from ethanol tolerant-dependent mice when 1,6-diphenyl-1,3,5-hexatriene was used as the probe, but not when 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene was used. These results indicate that chronic ingestion of ethanol decreased the fluidity and the ethanol sensitivity of the synaptic membranes. In contrast to the alterations observed with intact membranes, liposomes of lipids extracted from synaptic membranes of control and ethanol tolerant-dependent mice did not differ in their physical properties. Analysis of membrane lipids demonstrated that chronic ethanol treatment selectively decreased the unsaturated acyl groups of phosphatidylserine without altering the acyl composition of other phospholipids or sphingolipids. The amount of each phospholipid was not changed, but membrane cholesterol was decreased by chronic ethanol ingestion. Use of 2-dimensional thin-layer chromatography allowed the quantitation of 10 different gangliosides. The concentrations of these lipids were unchanged in synaptic membranes from ethanol tolerant-dependent mice. Thus, the changes in membrane physical properties produced by chronic ingestion of ethanol may be due, at least in part, to altered acyl composition of phosphatidylserine. The differences observed between intact membranes and extracted lipids suggest, however, that chronic ethanol treatment also produced changes in the lipid arrangement or lipid-protein interactions of the intact membranes.
TL;DR: Results suggest that CGRP in high doses may be centrally active in regulating consummatory behaviors and treated animals rested more, groomed less and ate less.
TL;DR: Quantitative analysis indicated that firing rate during ramp stimulation cannot, in general, be described by a simple linear combination of separate amplitude- and rate-dependent terms.
Abstract: Input-output relations of large neurons from layer V of cat sensorimotor cortex were studied in an in vitro slice preparation using steps and ramps of intracellularly injected current Depolarization attained during the interspike interval (ISI) was compared to the voltage levels required to activate a previously described (29) persistent sodium current (INaP) INaP was studied using a single-electrode voltage clamp in the same cells tested for firing behavior Following an injected current step, firing rate declined smoothly to a steady level with a time course that was approximately exponential in most cells (tau, 9-43 ms) In most cells, the relation between firing rate and injected current (f-I relation) consisted of two linear segments, both for adapted, steady firing and for early intervals during adaptation The slope of the steeper, initial (or sole) linear segment of the f-I curve averaged 262 Hz/nA during steady firing and was steeper when plotted for early interspike intervals The variation of the depolarization at which spike initiation occurred (firing level) and the membrane potential between rhythmic spikes was examined during adaptation and steady firing In most cells, firing level rose rapidly during a rhythmic train to a steady value The steady firing level attained remained unchanged over a wide range of steady firing rates Nevertheless, the mean depolarization during the interspike interval (V) increased approximately linearly with steady firing rate Even at the slowest firing rates, V is sufficient to activate INaP The use of injected current ramps demonstrated that neocortical cells were sensitive to rate of change of stimulus current (dI/dt) as well as its amplitude (I) The use of ramps followed by steady currents demonstrated that the repetitive response lagged behind changes in stimulus parameters and did not reach a steady state even during slow ramps; ie, the response depended on time as well as on I and dI/dt Instantaneous firing rate during the ramp increased linearly with time for a wide range of ramp slopes (dI/dt) The instantaneous firing rate of early interspike intervals was also linearly related to ramp slope for small ramp slopes In spite of these linear relationships, quantitative analysis indicated that firing rate during ramp stimulation cannot, in general, be described by a simple linear combination of separate amplitude- and rate-dependent terms The repetitive firing properties of the in vitro neurons are compared to those of in vivo neocortical neurons and other cell types(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: The deferoxamine infusion test is noninvasive, well tolerated, and of value particularly in excluding the diagnosis of aluminum-related osteodystrophy.
Abstract: The accumulation of aluminum in bone can cause disabling osteodystrophy in patients with renal failure. Because the chelating agent deferoxamine can mobilize aluminum from tissues, we evaluated the effect of a standard intravenous dose of deferoxamine on plasma aluminum concentrations in 54 patients on hemodialysis. Stainable bone aluminum, bone histologic findings, and bone aluminum content were studied. Baseline plasma aluminum concentrations of greater than 200 micrograms/L were associated with aluminum-related osteodystrophy (specificity, 93%), but concentrations of less than 200 micrograms/L did not exclude the diagnosis (sensitivity, 43%). After administration of deferoxamine, the increase in plasma aluminum concentration was 534 +/- 260 (SD) and 214 +/- 92 micrograms/L in patients with and without aluminum-related bone disease, respectively (p less than 0.001), and correlated with the bone aluminum content (r = 0.64). An increment in plasma aluminum concentration of greater than 200 micrograms/L identified 35 of the 37 patients with aluminum-related osteodystrophy; sensitivity was 94% and specificity, 50%. The deferoxamine infusion test is noninvasive, well tolerated, and of value particularly in excluding the diagnosis of aluminum-related osteodystrophy.
TL;DR: An unusual small intestinal tumor was found in a 61-year-old male who complained of intermittent right lower quadrant burning pain, tenesmus, and bloody diarrhea as discussed by the authors, the tumor was located intramurally in the distal jejunum with no involvement of the overlying mucosa.
Abstract: An unusual small intestinal tumor was found in a 61-year-old male who complained of intermittent right lower quadrant burning pain, tenesmus, and bloody diarrhea. On gross examination, the tumor was located intramurally in the distal jejunum with no involvement of the overlying mucosa. Histologic examination revealed two elements: a spindle cell component with characteristics reminiscent of a Schwann cell neoplasm, and nests of larger epithelioid-like cells almost undistinguishable from the Zellballen of nonchromaffin paragangliomas. The neoplasm originated within the intestinal wall without apparent mucosal origin. Ultrastructural studies revealed features recapitulating the normal enteric plexus structure and quite unlike those described in normal or neoplastic smooth muscle, Schwann or paraganglion cells. On this basis, this neoplasm is considered as a malignant enteric plexus tumor or a plexosarcoma.
TL;DR: This rapid but transient reduction in lymphocyte protein kinase activity restricted to modulation frequencies between 16 and 60 Hz and to less than 30 min exposure is consistent with "windowing" with respect to modulation frequency and exposure duration.
Abstract: Cultures of human tonsil lymphocytes were exposed in a Crawford cell to a 450-MHz field (peak envelope intensity 1.0 mW/cm2), sinusoidally amplitude modulated (depth 80%) at frequencies between 3 and 100 Hz for periods up to 60 min. The Crawford cell was housed in a temperature-controlled chamber (35 degrees C) and control cultures were placed in the same chamber. Activity of cAMP-dependent protein kinase relative to controls remained unaltered by fields modulated at 16 or 60 Hz with exposures of 15, 30, and 60 min. By contrast, total non-cAMP-dependent kinase activity fell to less than 50% of unexposed control levels after 15 and 30 min exposures, but, despite continuing field exposure, returned to control or preexposure levels by 45 and 60 min. A smaller reduction (20-25%) also occurred with 60-Hz modulation and was also restricted to exposure durations of 15 and 30 min. CW 450-MHz fields were without effect. Reduced enzyme activity occurred with 16-, 40-, and 60-Hz modulation frequencies, but not with 3-, 6-, 80-, or 100-Hz modulation. The specific identity of this kinase is unknown. This rapid but transient reduction in lymphocyte protein kinase activity restricted to modulation frequencies between 16 and 60 Hz and to less thanmore » 30 min exposure is consistent with ''windowing'' with respect to modulation frequency and exposure duration.« less
TL;DR: It is demonstrated that peripheral axotomy of DRG neurons produces spontaneous activity distinct from ongoing neuroma activity in a proportion of fibers which are potentially nociceptive (A&dgr;) as well as abnormal mechanosensitivity of the DRG.
Abstract: In 28 Sprague-Dawley rats, unilateral division of the sciatic nerve at the level of the midfemur was performed. Animals were observed for behavioral changes for 1-21 days, and electrophysiological recordings were made from microfilaments dissected from the ipsilateral L5 dorsal rootlets and sciatic nerve from 1 to 14 days postoperatively. Spontaneous discharges of two types were recorded: (1) variable frequency (0-100 Hz) discharges which typically occurred in rhythmic bursts and could be driven by mechanical stimulation of the neuroma; and (2) lower frequency (0.25-14 Hz) irregular activity which persisted after either excision or local anesthesia of the neuroma. The latter activity could also be recorded from the proximal cut end of the sciatic nerve following removal of the neuroma. The first type of activity was felt to be produced from the neuroma while the second originated in the region of the dorsal root ganglion (DRG). Analysis of the conduction velocities of fibers involved in each type of discharge indicated that both involved smaller myelinated filaments. However, the DRG activity involved significantly smaller fibers with conduction velocities in the A delta range. Spontaneous activity was recorded at 3 and 4 days for the neuroma and DRG activity, respectively. Ongoing discharges maximized at 7-10 days and were rare by 14 days. Autotomy of the ipsilateral foot was found to occur over a similar time course. Tetanic electrical stimulation (100 Hz) produced either little change in the baseline firing rate or prolonged afterdischarges in fibers manifesting neuroma activity. In fibers with ongoing activity of DRG origin, stimulation produced a stereotyped, brief low-frequency afterburst and then prolonged inhibition of firing. Mechanical stimulation of the neuroma produced both brief increases in spontaneous discharges and prolonged afterdischarges. In fibers with spontaneous DRG activity, minimal mechanical stimulation of their ganglion of origin produced high-frequency firing. This study demonstrates that peripheral axotomy of DRG neurons produces spontaneous activity distinct from ongoing neuroma activity in a proportion of fibers which are potentially nociceptive (A delta) as well as abnormal mechanosensitivity of the DRG. Furthermore, electrical stimulation of these fibers produces prolonged inhibition of the discharge. This finding may partially explain the prolonged relief of symptoms patients with chronic pain of peripheral origin may experience following peripheral tetanic electrical stimulation.
TL;DR: Dietary calcium supplementation significantly protected against gentamicin-induced renal tubular cell injury and, consequently, gentamic in-induced acute renal failure.
Abstract: The divalent cations, Ca++ and Mg++, are known to competitively inhibit a large number of aminoglycoside-membrane interactions, so that Ca++ prevents both the neurotoxic and ototoxic effects of these antibiotics acutely in vitro. Since gentamicin-induced plasma and subcellular membrane damage appear to be critical pathogenetic events in gentamicin nephrotoxicity, Ca++ may play a similar protective role in gentamicin-induced acute renal failure. To test this possibility in vivo, rats (group 2) were given a 4% calcium (in the form of CaCO3) supplemented diet to increase delivery of Ca++ to the kidney and administered single daily subcutaneous injections of gentamicin, 100 mg/kg, for 10 d. Compared with a simultaneously studied group (group 1) of rats receiving identical gentamicin dosages and normal diets, Ca++ supplementation ameliorated gentamicin-induced acute renal failure. After 10 doses of gentamicin, blood-urea nitrogen values in group 1 averaged 213 +/- 15 (SE) and 25 +/- 3 (P less than 0.001) in group 2. The progressive decline in renal excretory function, as measured by BUN, in group 1 animals was accompanied by simultaneous declines in renal cortical mitochondrial function and elevations in renal cortex and mitochondrial Ca++ content, quantitative indices of the degree of renal tubular cell injury. Oral Ca++ loading markedly attenuated these gentamicin-induced derangements. After eight and 10 doses of gentamicin, mitochondria isolated from the renal cortex of group 2 rats had significantly higher rates of respiration supported by pyruvate-malate, succinate and N,N,N',N'-tetramethyl-p-phenyldiamine-ascorbate, higher rates of dinitrophenol-uncoupled respiration and greater acceptor control ratios than those measured in mitochondria isolated from the renal cortex of group 1 animals. Similarly, after 8 and 10 doses, renal cortex and renal cortical mitochondrial Ca++ content of group 2 was significantly lower than values observed in group 1. Thus, dietary calcium supplementation significantly protected against gentamicin-induced renal tubular cell injury and, consequently, gentamicin-induced acute renal failure. The mechanism for this protective effect of Ca++ may relate to the manner in which this polycationic antibiotic interacts with anionic sites, primarily the acidic phospholipids of renal membranes. In this regard, Ca++ was found to be a competitive inhibitor both of 125I-gentamicin binding to renal brush border membranes, the initial site of interaction between gentamicin and renal proximal tubule cells, with a composite inhibition constant (Ki) of 12 mM and of 125I-gentamicin binding to phosphatidic acid, an important membrane acidic phosph
TL;DR: It is suggested that macrophages participating in inflammatory reactions in vivo might release IL-1, which could function to expand fibroblast populations at sites of inflammatory reactions, by acting as a fibro Blast growth factor.
Abstract: Human interleukin-1 (IL-1), free of contaminating lymphokines, was isolated from cultures of purified monoblasts from a patient with acute monocytic leukemia. Partially purified IL-1 (diafiltration, ultrafiltration, and isoelectric focusing) stimulated proliferation of subconfluent human fibroblasts in vitro. Further purification of IL-1 by high-resolution gel filtration- and anion exchange-high performance liquid chromatography revealed that fibroblast proliferation activity could not be separated from IL-1 activity (thymocyte proliferation), suggesting that both activities are the properties of a single molecule. Fibroblasts and thymocytes exhibited a similar sensitivity to the proliferative effects of IL-1. These findings suggest that macrophages participating in inflammatory reactions in vivo might release IL-1, which could function to expand fibroblast populations at sites of inflammatory reactions, by acting as a fibroblast growth factor.
TL;DR: Emphysema severity and scores for peripheral airways disease, except for goblet cell metaplasia, better distinguished SM-CAO from SM than did measures of bronchiole lumenal caliber, and within this group no morphologic or pathologic feature of the small airways was an independent predictor of ventilatory function beyond that of emphysemma alone.
Abstract: Despite the established role of cigarette smoking in the causation of chronic air-flow obstruction (CAO), only a small proportion of regular cigarette smokers develop significant clinical disease. We compared emphysema severity as well as pathologic and morphometric features of the peripheral conducting airways and the muscular pulmonary arteries among 3 groups of older subjects. These groups included lifelong nonsmokers (NSM), regular smokers without severe disease (SM), and smokers with an established diagnosis of CAO (SM-CAO). For most pathologic features examined there was an orderly progression in severity when comparing SM to NSM and SM-CAO to SM. Emphysema severity and scores for peripheral airways disease, except for goblet cell metaplasia, better distinguished SM-CAO from SM than did measures of bronchiole lumenal caliber. Within the SM-CAO group, the premortem percent predicted forced expiratory volume in one second (FEV1) correlated significantly with emphysema severity (r = 0.74), with average bronchiole diameter (r = 0.54), with the proportion of bronchioles with diameters less than 400 mu (r = 0.51), but not with any of the scores for bronchiolar disease. However, within this group no morphologic or pathologic feature of the small airways was an independent predictor of ventilatory function beyond that of emphysema alone. When compared with those from NSM, histological sections from SM-CAO lungs contained approximately twice as many fully muscularized artery profiles 0 to 300 mu in diameter, the arterial medial muscle layer was doubled in thickness, and the amount of arterial intimal fibrosis was tripled.(ABSTRACT TRUNCATED AT 250 WORDS)