Showing papers by "University of Texas Medical Branch published in 1980"

Muscarinic suppression of a novel voltage-sensitive K + current in a vertebrate neurone

Abstract: Cholinergic excitation of vertebrate neurones is frequently mediated through the action of acetylcholine on muscarinic (atropine-sensitve) receptors. This type of excitation differs substantially from the better known nicotinic excitation. One difference is that, instead of an increased membrane conductance, a decreased conductance (to K+ ions) frequently accompanies muscarinic depolarisation. This has been detected in sympathetic, cortical and hippocampal neurones. Using voltage-clamped frog sympathetic neurones we have now identified a distinctive voltage-sensitive K+-current, separate from the delayed rectifier current, as the prime target for muscarinic agonists. We have termed this current the M-current, IM.

A Mechanism for the Amelioration by Hyperbaric Oxygen of Experimental Staphylococcal Osteomyelitis in Rabbits

Abstract: Although hyperbaric oxygen (HBO) is as effective as cephalothin against osteomyelitis due to Staphylococcus aureus in the rabbit, the effect is not by directing killing. To investigate the mechanism, argon washouts (perfusion) and oxygen tensions were measured by intramedullary probes placed in the metaphyses of infected and uninfected tibias. In vitro phagocytic killing activity for S. aureus was determined at oxygen tensions found in these bones under ambient and HBO conditions. Mean tibial oxygen tensions (mm Hg) under ambient conditions were 21 (infected) and 45 (uninfected); under HBO conditions, 104 (infected) and 321 (uninfected). Perfusion was decreased in osteomyelitic bone and was not acutely increased by HBO in either normal or infected bone. Phagocytic killing of S. aureus was markedly decreased at 23 mm Hg of O2, significantly improved at 45 and 109 mm Hg, and most effective at 150 mm Hg. Thus, in osteomyelitic bone, HBO increased intramedullary oxygen to tensions consistent with normal phagocytic function.

Covalent structure of human haptoglobin: a serine protease homolog

Abstract: The complete amino acid sequences and the disulfide arrangements of the two chains of human haptoglobin 1-1 were established. The alpha 1 and beta chains of haptoglobin contain 83 and 245 residues, respectively. Comparison of the primary structure of haptoglobin with that of the chymotrypsinogen family of serine proteases revealed a significant degree of chemical similarity. The probability was less than 10(-5) that the chemical similarity of the beta chain of haptoglobin to the proteases was due to chance. The amino acid sequence of the beta chain of haptoglobin is 29--33% identical to bovine trypsin, bovine chymotrypsin, porcine elastase, human thrombin, or human plasmin. Comparison of haptoglobin alpha 1 chain to activation peptide regions of the zymogens revealed an identity of 25% to the fifth "kringle" region of the activation peptide of plasminogen. The probability was less than 0.014 that this similarity was due to chance. These results strongly indicate haptoglobin to be a homolog of the chymotrypsinogen family of serine proteases. Alignment of the beta-chain sequence of haptoglobin to the serine proteases is remarkably consistent except for an insertion of 16 residues in the region corresponding to the methionyl loop of the serine proteases. The active-site residues typical of the serine proteases, histidine-57 and serine-195, are replaced in haptoglobin by lysine and alanine, respectively; however, aspartic acid-102 and the trypsin specificity, residue, aspartic acid-189, do occur in haptoglobin. Haptoglobin and the serine proteases represent a striking example of homologous proteins with different biological functions.

Responses of neurons in primate ventral posterior lateral nucleus to noxious stimuli

Abstract: 1. Recordings were made from the caudal part of the ventral posterior lateral (VPLc) nucleus of the thalamus in anesthetized macaque monkeys. In additon to many neurons that responded only to weak mechanical stimuli, scattered neurons were found that responded to both innocuous and noxious stimulation or just to noxious stimulation of the skin. A total of 73 such neurons were examined in 26 animals. 2. Noxious stimuli included strong mechanical stimuli (pressure, pinch, and squeezing with forceps) and graded noxious heat (from 35 degrees C adapting temperature to 43, 45, 47, and 50 degrees C). The responses of the VPLc neurons increased progressively with greater intensities of noxious stimulation. The stimulus-response function when noxious heat stimuli were used was a power function with an exponent greater than one. 3. Repetition of the noxious heat stimuli revealed sensitization of the responses of the thalamic neurons to such stimuli. The threshold for a response to noxious heat was lowered, and the responses to supra-threshold noxious heat stimuli were enhanced. 4. The responses of VPLc neurons to noxious heat stimuli adapted after reaching a peak discharge frequency. The rate of adaptation was slower for a stimulus of 50 degrees C than for one of 47 degrees C. 5. For the six neurons tested, responses to noxious heat were dependent on pathways ascending in the ventral part of the lateral funiculus contralateral to the receptive field (ipsilateral to the thalamic neuron). In two cases, the input to the thalamic neurons from axons of the dorsal column was also conveyed by way of a crossed pathway in the opposite ventral quadrant. In another case, access to the thalamic neuron by way of ascending dorsal column fibers was demonstrated. 6. The thalamic neurons had restricted contralateral receptive fields that were somatotopically organized. Neurons with receptive fields on the hindlimb were in the lateral part of the VPLc nucleus, whereas neurons with receptive fields on the forelimb were in medial VPLc. 7. Ninety percent of the VPLc neurons tested that responded to noxious stimuli could be activated antidromically by stimulation of the surface of SI sensory cortex. It was possible to confirm that many of these cells project to the SI sensory cortex by using microstimulation. Successful microstimulation points were either within the SI cortex or in the white matter just beneath the cortex. 8. We conclude that some neurons in the VPLc nucleus are capable of signaling noiceptive stimuli. The nociceptive information appears to reach these cells through the ventral part of the lateral funiculus on the side contralateral to the receptive field, presumably by way of the spinothalamic tract. The VPLc cells are somatotopically organized, and they are thalamocortical neurons that project to the VPLc nucleus and SI cortex play a role in nociception.

Studying programmer behavior experimentally: the problems of proper methodology

Abstract: The application of behavioral or psychological techniques to the evaluation of programming languages and techniques is an approach which has found increased applicability over the past decade. In order to use this approach successfully, investigators must pay close attention to methodological issues, both in order to insure the generalizability of their findings and to defend the quality of their work to researchers in other fields. Three major areas of methodological concern, the selection of subjects, materials, and measures, are reviewed. The first two of these areas continue to present major difficulties for this type of research.

The Marital Status Inventory: Development of a Measure of Dissolution Potential.

Abstract: The development of a 14-item intensity scale measuring likelihood of marriage dissolution is described. The Marital Status Inventory (MSI) forms a Guttman-like scale. Preliminary discriminant validity data are presented for the self-report scale indicating that couples presenting with marital problems score significantly higher than couples seeking parent-child related therapy. The predictive validity of the scale remains to be demonstrated, but the MSI is reported for use by researchers and clinicians.

The use of potassium ferricyanide in neural fixation

Abstract: The present study suggests a mixture of buffered osmic acid and 1.5% potassium ferricyanide as a post-fixation to improve the fixation of neural tissue. This procedure results in an improved preservation of membranes as well as cytoplasm and cytoplasmic organelles. It is to be emphasized that the quality of the initial perfusion is the primary determinant of quality of the fixation, but the addition of 1.5% potassium ferricyanide to post-fixation fluid makes good fixation better and allows data to be gathered from otherwise unusable material.

The Somatomedin C Binding Protein: Evidence for a Heterologous Subunit Structure*

Abstract: The binding of somatomedin C to serum proteins was investigated using Sephadex G-200 chromatography at pH 7.40. Under these conditions, immunoreactive somatomedin C in whole serum has a Stokes' radius of 43 A (Kd = 0.25). After ammonium sulfate precipitation and DEAE Sephadex chromatography, three protein peaks were obtained. The second peak contained the majority of the immunoreactive somatomedin C, but the somatomedin in this fraction has Stokes' radii of 36 and 14 A (Kd = 0.35 and 0.75, respectively). Recombining this fraction with the DEAE Sephadex peak 3 fraction resulted in the reappearance of the 43 A (Kd = 0.25) species. Chromatography of the 43 A somatomedin C species on Sephadex G-50 in 0.1 M acetic acid-0.15 M NaCl dissociated somatomedin C from its binding protein. The binding protein was recovered in the void volume fractions of the G-50 column. This acid-treated binding protein had a Stokes' radius of 36 A (Kd = 0.35), as determined by the binding of [l25I]somatomedin C at pH 7.40. When the ...

Neurological course and correlated computerized tomography findings after severe closed head injury

Abstract: ✓ This study includes 124 patients with closed head injuries and with Glasgow Coma Scale (GCS) scores of ≤ 8, who were admitted over a 7 1/2-month period. The time at which death occurred after injury was bimodal: deaths occurred either within 48 hours or after 7 days or longer after injury. Neurological deterioration, however, occurred with equal frequency on Days 2 to 7 after injury. Patients who survived the first 48 hours and then suffered neurological deterioration did not differ from the total population in age, sex, GCS scores on admission, or pupillary reactivity, but had a much higher incidence of intracranial hematomas of all types. Deterioration occurred three times more frequently in those with hematomas than in those with diffuse brain injury. Patients who deteriorated were rarely among the 35% of those who rapidly improved in the first 48 hours (4 points or more on the GCS). Computerized tomography (CT) scans of those deteriorating (24 patients) could be divided into four categories: 1) thos...

Neuronal increase in various areas of the nervous system of the guppy, Lebistes

Abstract: The numbers of 1) dorsal root ganglion cells in the 2nd spinal segment, 2) ventral horn cells in the 2nd spinal segment, 3) Purkinje cells of the cerebellum, and 4) neurons in the nucleus glomerulosus were counted and correlated with age and size in the guppy, Lebistes. The findings were that the neuronal numbers in all these areas increased throughout much of the life of the animal. These data, combined with the previously demonstrated increases in retinal neurons in goldfish and sensory and spinal neurons in stingrays, suggest that neurons are added to many areas of the nervous system of fish as the animal ages and grows. In this respect, the nervous systems of fish differ from the nervous systems of other vertebrates. We offer the suggestion that the comparatively greater ability of fish to regenerate their nervous system after injury may be related in part to their ability to add neurons to various parts of the nervous system throughout life.

Luteinizing hormone-releasing factor and muscarinic agonists act on the same voltage-sensitive K+-current in bullfrog sympathetic neurones.

Abstract: The effect of bath-applied luteinizing hormone-releasing factor (LHRF) was recorded in voltage-clamped bullfrog lumbar sympathetic neurones. At a holding potential of -- 30 mV, LHRF induced a steady inward (depolarizing) current and reduced membrane conductance; at -- 60 mV LHRF produced negligible inward current and much less conductance change. The effects of LHRF were accompanied by a reduced amplitude of the slow current relaxations following hyperpolarizing and depolarizing commands, without prominent change in their time-course. This suggests a selective depression of the voltage-sensitive outward K+-current which is suppressed by muscarinic agonists.

Common pathways of interferon and hormonal action.

Abstract: The action of interferon1 as well as polypeptide hormones2 has been shown to be transmissible between cells, possibly through gap-junctional transfer of secondary messenger molecules. This and other similarities between interferon and polypeptide hormones3 have led us to propose that there is a common cellular pathway of interferon and hormonal action. If correct, this hypothesis would predict that interferon should cause a species-specific hormonal response and a hormone should induce tissue-specific antiviral activity. If these two responses are mediated by similar secondary messengers, they should be transmissible and cross-activate cells. Here, we show that interferon caused a species-specific hormonal response (noradrenaline-like stimulation of the beat frequency of cultured mouse myocardial cells). Noradrenaline induced an interferon-like antiviral state in mouse myocardial cells but not human amnion (WISH) cells. In conditions which demonstrate interferon-induced transfer of viral resistance, exposure of co-cultures of mouse myocardial cells and WISH cells to either human interferon or noradrenaline caused an increased beat frequency in the myocardial cells and development of antiviral activity in WISH cells, respectively. These studies strongly suggest common pathways of interferon and hormonal stimulation that are transmissible between cells.

Segmental localization of sensory cells that innervate the bladder

Abstract: The present study labels the neuronal cell bodies that give rise to afferent fibers that innervate the bladder of cat and rat. The method used was the retrograde transport of horseradish peroxidase (HRP) from its injection site in the bladder to cells in the various dorsal root ganglia. In the rat, the labelled cells are located in the L1–L2 and L6–S1 dorsal root ganglia. In the cat, the labelled cells are located in the L2–L5 and S1–S4 dorsal root ganglia. This confirms older clinical findings, and for the first time directly demonstrates the afferent cell bodies for the bladder. The bladder afferents are small ganglion cells in both rat and cat, and because there is a correlation between the size of axon and the cell body from which it originates, we conclude that the great majority of bladder afferents are small myelinated or unmyelinated axons. In addition, by restricting the HRP to one side of the bladder, we were able to show that some afferent cell bodies send their distal processes across the midline. These results will be useful in considerations of the neural control of bladder function.

A sensitive radioenzymatic assay for catechol drugs.

Abstract: This assay measures picogram quantities of catechol drugs and endogenous catecholamines in body tissues and fluids. The catechols are converted to their 3H-O-methyl metabolites during incubation with 3H-S-adenosylmethionine then separated by solvent extraction and thin-layer chromatography. Most drugs containing the catechol structure can be radiolabeled and separated from norepinephrine and epinephrine by this technique to provide simultaneous measurement of endogenous and exogenously administered catechols. The disposition of isoproterenol in tissues and fluids of man and experimental animals is measured to illustrate the utility of this assay. The reactivity of several commonly administered catechol drugs with COMT is described and the possible implications discussed.

Leg 67: The Deep Sea Drilling Project Mid-America Trench transect off Guatemala

Abstract: Drill cores from a transect of the Mid-America Trench off Guatemala were obtained at three sites on the oceanic Cocos plate, and at four sites on the continental Caribbean plate. An ocean sub-bottom seismometer was successfully emplaced in the deepest hole in the trench landward slope where it was left to record data after departure of the drill ship. Drilling on the Cocos plate recovered a basal chalk sequence deposited during early and mid-Miocene time, a short interval of abyssal red clay, and an upper sequence of late Miocene and younger sediment deposited within an area influenced by a terrigenous source. In the trench, a mud and sand fill less than 400,000 yr old overlies the oceanic sequence. The entire section shows no evidence of compressive deformation even at holes drilled against the trench9s landward slope. In contrast, the section cored on the trench9s landward slope 3 km from the trench axis is affected by tectonism. The section contains a Cretaceous to Pliocene claystone sequence, broken by hiatuses but in a normal stratigraphic succession that is capped by Pliocene to Quaternary hemipelagic slope deposits. Seismic records show that the section overlies probable igneous oceanic crust from which it is separated by a few hundred metres. That thickness of undrilled section is insufficient to accommodate the potential offscraped volume of oceanic sediment carried into the trench during Neogene plate convergence. At the estimated 10 cm/yr rate of convergence, much of the oceanic sediment must have been subducted rather than tectonically accreted to the Guatemalan margin. Current models for convergent margin tectonics do not satisfactorily explain the surprising occurrence of Cretaceous to Miocene mudstone at the base of this trench slope. The recovery of gas hydrates prevented drilling to some landward-dipping reflections presumed to be imbricate thrust slices at two sites near the middle of the trench landward slope.

Baroreceptor Function and Changes in Strain Sensitivity in Normotensive and Spontaneously Hypertensive Rats

Abstract: SUMMARY Baroreceptor resetting during hypertension has been attributed to a reduction in the distensibility of the vessel wall in which the receptors are located. According to this hypothesis, a simple increase in pressure is all that is required to overcome the increase in vessel wall stiffness. However, previous work from our laboratory suggested a more complicated situation. Measurements of both vessel wall mechanical properties and baroreceptor discharge characteristics in spontaneously hypertensive rats (SHR) showed that distortion thresholds for the receptors also undergo changes. Here we have examined the time course of resetting, measuring both aortic distensibility and baroreceptor properties in SHR and mormotensive Wistar-Kyoto rats (WKY) from 5 to 30 weeks in age. An in vitro aortic arch-aortic nerve preparation was used. We found that for a given pressure the aortic radii of WKY were increasing much more rapidly than the aortic radii for SHR and, beyond 5 weeks of age, were much more distensible. The lower distensibility in SHR was accompanied by increased wall thickness. The discharge characteristics of single baroreceptors were expressed in terms of both pressure and distortion or circumferential wall strain. The change in distensibility of WKY aortas from 5 to 30 weeks was suitably matched by an increase in the strain threshold for discharge of WKY baroreceptors resulting in a constant pressure threshold for discharge. The lower distensibility of SHR aortas was accompanied by lower threshold strains in SHR baroreceptors, but the changes were not suitably matched, and progressive resetting of SHR baroreceptors to higher threshold pressures occurred. The two sets of receptors appear to be different as early as 5 weeks of age when blood pressures are similar and, futhermore, these differences are accentuated by age and hypertension. CircRes 47: 821-828, 1980

Inhibition and excitation of primate spinothalamic tract neurons by stimulation in region of nucleus reticularis gigantocellularis.

Abstract: 1. Electrical stimulation in the region of the nucleus reticularis gigantocellularis (NGc) in anesthetized monkeys inhibited or excited spinothalamic tract neurons in the lumbosacral and cervical enlargements. 2. The descending effects were generally more pronounced for activity evoked by cutaneous A-delta-fibers than for activity produced by large myelinated cutaneous afferents. Nevertheless, the responses to all types of natural stimuli used could be inhibited or facilitated. 3. The excitation from repeated brief stimulus trains to the NGc sometimes increased progressively, suggesting the existence of a positive feedback system. Occasionally, repeated stimulation of the NGc produced a progressively greater inhibition. 4. The threshold stimulus strength to elicit the inhibitory and excitatory actions was usually less than 50 microA, and in some cases less than 25 microA. The inhibition and excitation increased as the stimulus intensity was raised above the threshold value, or as the number and/or frequency of pulses in the stimulus train was increased. 5. The strongest inhibition and excitation was produced by stimulation within the NGc on either side of the brain stem. There was no obvious topographic organization of inhibitory and excitatory zones. 6. Dorsolateral tractotomies in the high cervical spinal cord did not prevent the effects of NGc stimulation, indicating that the inhibitory and excitatory pathways descend in the ventral parts of the white matter. 7. It is suggested that the inhibition and excitation are mediated by the medullary reticulospinal system.

Diminished Immune Response in Sun-Damaged Skin

Abstract: In previously sensitized volunteers, higher concentrations of 2,4-dinitrochlorobenzene were necessary to elicit positive patch test reactions on the sun-damaged skin of the neck than on the protected skin of the upper part of the back. This difference was not found in subjects without evidence of sun damage, and there was no difference between sun-damaged and nondamaged skin in response to a primary irritant. Responses to intradermally injected common antigens were also less intense in sun-damaged skin that in nonexposed skin. These findings suggest the existence of a local defect in cell-mediated immunity in skin altered by long-term sun exposure.

Potentiation of Antitumor Effect of Virus-Induced Interferon by Mouse Immune Interferon Preparations

Abstract: In inbred DBA/2 mice, the antitumor activities of separate and combined preparations of mouse immune interferon and mouse virus-induced interferon on the development of P388 tumors were studied. Immune interferon alone (25 U/day) did not affect tumor development. Virus-induced interferon alone (25,000 U/day) delayed tumor development and increased survival time. The mouse immune interferon preparations significantly enhanced or potentiated the antitumor effects of mouse virus-induced interferon when the interferons were used in combined therapy.

Efferent projections of the deep mesencephalic nucleus (pars medialis) in the rat.

Abstract: The projections of the medial part of the deep mesencephalic nucleus (DMN) were traced by autoradiography and retrograde horseradish peroxidase (HRP) techniques. No ascending projections were observed from the medial part of the DMN; however, two groups of descending fibers were observed. One group crossed the midline and coursed to the caudal part of the red nucleus. At this point, these fibers divided into two distinct bundles. One bundle of fibers passed caudally to terminate in the contralateral pontine reticular nucleus, superior olive-trapezoid body complex, gigantocellular nucleus, and upper cervical spinal cord. The other bundle entered the medial longitudinal fasciculus (MLF) and coursed through the pons and medulla without termination, to enter the cervical spinal cord where terminations were noted in the dorsal horn. The other group of fibers from the medial DMN descended through the ipsilateral pons and medulla, projecting to the pontine reticular nucleus, superior olive-trapezoid body complex, gigantocellular nucleus, and upper cervical spinal cord. These findings indicate that the medial part of the DMN is likely to be involved in complex sensorimotor events via reticulobulbar and reticulospinal connections.

Immune and virus-induced interferons may activate cells by different derepressional mechanisms.

Abstract: Virus-induced interferon (VIF), and immune interferon (IIF) produced by lymphocytes following activation by various mitogens (phytohaemagglutinin, concanavalin A, staphylococcal enterotoxin A) or by specific antigenic stimulation (tuberculin, bacterial toxoids, and viral antigens) show important functional differences. These include different antitumour1 and immunoregulatory activities2 and differential inhibition of activity by mercaptoethanol3. Another important difference has recently been shown: cells treated with IIF acquire the antiviral state much more slowly than those treated with VIF4. This may be due to (1) difference in cellular receptors, (2) presence of an inhibitor of antiviral activity in the IIF preparations, or (3) a different mechanism of activation of the antiviral state by the two types of interferon. The first two hypotheses seem unlikely, since (1) no difference between cell association by the two types of interferon has been detected4, and (2) the presence of the slow acting IIF preparation did not inhibit the rapid activation by VIF4. The present study shows that the different kinetics of induction of the antiviral state result from a major difference in the mechanism by which IIF and VIF activate cells.