scispace - formally typeset
Search or ask a question

Showing papers by "Oregon Health & Science University published in 1988"


Journal ArticleDOI
01 Dec 1988-Nature
TL;DR: This receptor has been characterized on the basis of three criteria: the deduced amino-acid sequence which reveals that it is a member of the family of G-protein-coupled receptors; the tissue distribution of the mRNA which parallels that of the D2 dopamine receptor; and the pharmacological profile of mouse fibroblast cells transfected with the cDNA.
Abstract: Dopamine receptors are classified into D1 and D2 subtypes on the basis of their pharmacological and biochemical characteristics. The D2 dopamine receptor has been implicated in the pathophysiology and treatment of movement disorders, schizophrenia and drug addiction. The D2 dopamine receptor interacts with guanine nucleotide-binding proteins to induce second messenger systems. Other members of the family of receptors that are coupled to G proteins share a significant similarity in primary amino-acid sequence and exhibit an archetypical topology predicted to consist of seven putative transmembrane domains. We have taken advantage of the expected nucleotide sequence similarities among members of this gene family to isolate genes coding for new receptors. Using the hamster beta 2-adrenergic receptor gene as a hybridization probe we have isolated related genes including a cDNA encoding the rat D2 dopamine receptor. This receptor has been characterized on the basis of three criteria: the deduced amino-acid sequence which reveals that it is a member of the family of G-protein-coupled receptors; the tissue distribution of the mRNA which parallels that of the D2 dopamine receptor; and the pharmacological profile of mouse fibroblast cells transfected with the cDNA.

1,148 citations


Journal ArticleDOI
TL;DR: Information is provided on how the properties of DHA-rich Membranes, including their biophysical properties, affect their ability to secrete non-volatile substances such as polyene and polymethine.
Abstract: INTRODUCTION 517 TISSUE DISTRIBUTION ........ ....... 519 ACCUMULATION DURING DEVELOPMENT 521 DIETARY DEFICIENCY 523 Studies in Rats . . . . . . . . . ... . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523 Studies in Nonhuman Primates. . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 526 Human Case Studies . . . . . . . . .. . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 528 FUNCTIONAL EFFECTS IN BIOLOGICAL MEMBRANES 528 Biophysical Properties of DHA-rich Membranes . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . 529 Effects on Enzyme Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530 Lipoxygenase Products of DHA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . 531 Lipid Peroxidation . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532 CONCLUSIONS AND IMPLICATIONS 532

748 citations


Journal Article
TL;DR: The efficacy of cryotherapy is supported in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP.
Abstract: We report the preliminary three-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied in one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30 degrees sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of \"plus\" disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined three months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP.

625 citations


Journal ArticleDOI
TL;DR: Investigation in the Rochester, Minnesota, population over the period 1950–1982 found that Torticollis was the most common focal dystonia; essential blepharospasm, oromandibular dySTONia, spasmodic dysphonia, and writer's cramp were less common and had roughly equal incidence and prevalence rates.
Abstract: The epidemiology of generalized and focal dystonias was investigated in the Rochester, Minnesota, population over the period 1950-1982. The crude incidence of generalized dystonia was 2 per million persons per year, and for all focal dystonias combined, 24 per million per year. The crude prevalence rate was 34 per million persons for generalized dystonia and 295 per million persons for all focal dystonias. Torticollis was the most common focal dystonia; essential blepharospasm, oromandibular dystonia, spasmodic dysphonia, and writer's cramp were less common and had roughly equal incidence and prevalence rates.

427 citations


Journal ArticleDOI
TL;DR: Risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages, and radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia.
Abstract: The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder (relative risk (RR) = 4.0), rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer wasmore » observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors.« less

389 citations


Journal ArticleDOI
TL;DR: It is concluded that gamma E evolved into gamma F in stem-simians and an elevated non-synonymous substitution rate characterizes this transition.

354 citations


Journal ArticleDOI
TL;DR: It is concluded that activation of both dopamine D2 and GABAB receptors may increase the same potassium conductance in rats injected with pertussis toxin.
Abstract: 1. Intracellular recordings were made from 193 substantia nigra zona compacta neurones in slices of rat mesencephalon. All cells were hyperpolarized by baclofen; this was accompanied by a fall in input resistance. Cells voltage clamped at -60 mV showed an outward current associated with a conductance increase in response to baclofen. The baclofen effects were concentration dependent (effective range 0.3-30 microM); the concentration producing half the maximal effect was 1.5 microM. (-)-Baclofen was 300-700 times more potent than (+)-baclofen. 2. The potential change or membrane current caused by baclofen reversed polarity at -108.8 +/- 1.1 mV (n = 10) when the potassium ion concentration was 2.5 mM, -96.0 +/- 2.8 mV (n = 3) in 4.5 mM-potassium and -76.6 +/- 1.7 mV (n = 5) in 10.5 mM-potassium. The relationship between reversal potential and potassium concentration conformed to the Nernst equation. 3. Dopamine was also applied to 119 of these neurones; all exhibited either a hyperpolarization or an outward current. 4. Baclofen and dopamine outward currents were reduced reversibly by barium (100-300 microM) and tetraethylammonium (10 mM). Superfusion for 5-10 min with solutions presumed to block calcium currents reduced, but did not abolish, responses to baclofen. The effect of baclofen persisted in tetrodotoxin (1 microM). 5. Superfusion of gamma-aminobutyric acid (GABA, 0.3-3 mM) caused either membrane depolarization or hyperpolarization, accompanied by a fall in input resistance. The depolarization was mimicked by muscimol (10 microM) and blocked by bicuculline methiodide (10-100 microM); the hyperpolarization was resistant to bicuculline. Nipecotic acid (500 microM) enhanced the effect of GABA, but was without effect upon the actions of muscimol and baclofen. 6. The effect of dopamine was enhanced by cocaine (10 microM) and antagonized by (-)-sulpiride (0.1-1 microM), whereas the actions of baclofen were unaffected by cocaine or (-)-sulpiride. The maximum outward current produced by dopamine was approximately half that produced by baclofen. 7. Outward currents produced by dopamine were reversibly occluded by maximal outward currents caused by baclofen. 8. Baclofen and dopamine hyperpolarizations were unaffected by intracerebroventricular injection of animals with pertussis toxin. 9. Cells impaled with electrodes containing guanosine 5'-O-(3-thiotriphosphate) (1 mM) were hyperpolarized by both baclofen and dopamine, but the membrane potential did not fully return to its original level when agonist application was discontinued. 10. It is concluded that activation of both dopamine D2 and GABAB receptors may increase the same potassium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

347 citations


Journal ArticleDOI
TL;DR: Spectroscopically characterize the oxidized states of MnP compounds I, II, and III and clarify the role of Mn in the catalytic cycle of the enzyme, indicating that Mn(II) serves as an obligatory substrate for MnP compound II, allowing the enzyme to complete its catalysttic cycle.
Abstract: Manganese peroxidase (MnP), an extracellular heme enzyme from the lignin-degrading fungus Phanerochaete chrysosporium, catalyzes the Mn(II)-dependent oxidation of a variety of phenols. Herein, the authors spectroscopically characterize the oxidized states of MnP compounds I, II, and III and clarify the role of Mn in the catalytic cycle of the enzyme. Addition of 1 equiv of H/sub 2/O/sub 2/ to the native ferric enzyme yields compound I, characterized by absorption maxima at 407, 558, 605, and 650 nm. Addition of 2 or 250 equiv of H/sub 2/O/sub 2/ to the native enzyme yields compound II or III, respectively, identified by absorption maxima at 420, 528, and 555 nm or at 417, 545, and 579 nm, respectively. These characteristics are very similar to those of horseradish peroxidase (HRP) and lignin peroxidase (LiP) compounds I, II, and III. Addition of 1 equiv of either Mn(II), ferrocyanide, or a variety of phenols to MnP compound I rapidly reduces it to MnP compound II. In contrast, only Mn(II) or ferrocyanide, added at a concentration of 1 equiv, reduces compound II. The Mn(III) produced by the enzymic oxidation of Mn(II) oxidizes the terminal phenolic substrates. This indicates that compounds I and II of MnP contain 2more » and 1 oxidizing equiv, respectively, over the native ferric resting enzyme and that the catalytic cycle of the enzyme follows the path native enzyme ..-->.. compound I ..-->.. compound II ..-->.. native enzyme. In addition, these results indicate that Mn(II) serves as an obligatory substrate for MnP compound II, allowing the enzyme to complete its catalytic cycle. Finally, the Mn(II)/Mn(III) redox couple enables the enzyme to rapidly oxidize the terminal phenolic substrates.« less

314 citations


Journal ArticleDOI
TL;DR: The results suggest that chronic (but not acute) intake of fish oil may inhibit the synthesis or secretion of chylomicrons from the gut, however, accelerated clearance due to decreased VLDL competition cannot be excluded.

306 citations


Journal ArticleDOI
TL;DR: The active participation of opioid neurons, especially those containing dynorphin, at the spinal level, in the modulation of sensory afferent input during peripheral inflammatory pain states is suggested.

275 citations


Journal ArticleDOI
TL;DR: Emotional disturbances and executive disorders associated with the site or nature of the lesion(s) affect patients' interaction with their families differentially creating distinctive patterns of family burden.
Abstract: Behavioral alterations due to brain damage that compromise the quality of patients' lives also affect the well-being of patients' families. Family distress following head injury has been well-documented. With other cerebral disorders, similar emotional burdens and family disruptions are experieneced by the immediate family. Most families suffer many of the core problems arising from the patient's dependency and cognitive inefficiency, and from social reactions to the patient's disability. Moreover, emotional disturbances and executive disorders associated with the site or nature of the lesion(s) affect patients' interaction with their families differentially creating distinctive patterns of family burden. Specific family problems may be relieved through education, counselling, and emotional support.


Journal ArticleDOI
TL;DR: The results indicate that a common potassium conductance is increased by 5-HT acting on 5- HT 1 receptors and baclofen acting on GABA-B receptors, which differs from the other form of inward rectification (IIR) in its voltage dependence and sensitivity to pertussis toxin.
Abstract: Intracellular recordings were made from neurons in rat dorsal raphe in the slice preparation maintained at 37 degrees C. The single-electrode voltage-clamp method was used to measure membrane currents at potentials more negative than rest (-60 mV). Three types of inward rectification were observed: 2 in the absence of any drugs and the third induced by 5-HT 1 and GABA-B receptor agonists. In the absence of any drugs, an inward current activated over 1–2 sec when the membrane potential was stepped to potentials more negative than -70 mV. This current was blocked by cesium (2 mM) and resembles IQ or IH. A second inward current (IIR) occurred at membrane potentials near the potassium equilibrium potential (EK). This inward current activated within the settling time of the clamp and was abolished by both barium (10–100 microM) and cesium (2 mM). 5-HT 1 agonists activated a potassium conductance that hyperpolarized the cells at rest. This potassium conductance was about 2 nS at -60 mV and increased linearly with membrane hyperpolarization to about 4 nS at -120 mV. Baclofen activated a potassium conductance identical in amplitude and voltage dependence to that induced by 5-HT 1 agonists. Both the baclofen- and 5-HT-induced currents were nearly abolished in animals pretreated with pertussis toxin. The results indicate that a common potassium conductance is increased by 5-HT acting on 5-HT 1 receptors and baclofen acting on GABA-B receptors. This potassium conductance rectifies inwardly and is distinct from the Q-current. The ligand-activated potassium conductance also differs from the other form of inward rectification (IIR) in its voltage dependence and sensitivity to pertussis toxin.

Journal ArticleDOI
TL;DR: The data indicate that the mean threshold irradiance for suppressing melatonin is between 1.6 and 5 microW/cm2, and individual variations in threshold responses to monochromatic light were observed among the volunteers.

Journal ArticleDOI
TL;DR: Serum and saliva could not discriminate between nonsmokers and passive smokers, and cotinine in all body fluids could separate active smokers from the other two groups.
Abstract: Cotinine was measured in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers. Serum and saliva could not discriminate between nonsmokers and passive smokers. Mean urine cotinine was higher in passive smokers than nonsmokers but there was a great deal of intersubject overlap. Cotinine in all body fluids could separate active smokers from the other two groups. Among smokers, light smokers had lower levels than heavier smokers.


Journal ArticleDOI
TL;DR: Data from this study are consistent with the concept of a receptor-mediated autocrine or paracrine role for progestins, but not estrogens in the gametogenic and endocrine functions of the primate ovary throughout the menstrual cycle.
Abstract: Both estradiol and progesterone may act locally to modulate ovarian function in various species. This study examined the distribution of estradiol and progesterone receptors (ER and PR, respectively) within the primate ovary throughout the menstrual cycle. Ovaries were collected from rhesus or cynomolgus monkeys during the early, mid-, and late (n = 3-6/stage) follicular and luteal phases of the cycle. The tissues were processed for indirect immunocytochemical localization of receptors with specific monoclonal antibodies against ER (H222 and D75) and PR (JZB39). Specific immunocytochemical staining, as determined by comparing adjacent tissue sections incubated with either receptor antibodies or a nonspecific antibody, was exclusively nuclear. Both ER and PR were localized in the germinal epithelium of ovaries at all stages of the cycle. ER was not detected in any other ovarian structure (i.e. stroma, follicles, interstitial tissue, or corpora lutea) regardless of the stage of development. However, ER was detected in other estrogen-responsive tissues, e.g. the oviduct of the monkey and corpora lutea of the pseudopregnant rabbit. In the monkey ovary, PR was detected in stromal and interstitial tissues as well as theca interna and externa of healthy and atretic follicles at all stages of the cycle. The granulosa cells of some primordial and primary follicles demonstrated staining for PR. However, the granulosa layer of follicles that developed beyond the primary stage were consistently negative for PR. Only the granulosa layer of large preovulatory follicles that showed signs of luteinization after the LH surge showed staining for PR equivalent to that in the theca. Monkey corpora lutea exhibited specific nuclear staining for PR. Moreover, the percentage of receptor-positive nuclei in the corpus luteum varied (P less than 0.05) between the early (28 +/- 3%), mid (48 +/- 1%)-, and late (4 +/- 2%) luteal phase of the cycle. Nonfunctional (serum progesterone less than 0.5 ng/ml) regressing corpora lutea did not exhibit for staining for PR. Luteal cells that were PR positive also contained histochemically detectable 3 beta-hydroxysteroid dehydrogenase. These data are consistent with the concept of a receptor-mediated autocrine or paracrine role for progestins, but not estrogens in the gametogenic and endocrine functions of the primate ovary throughout the menstrual cycle.

Journal ArticleDOI
TL;DR: Modified positioning for women with breast implants substantially improves both image quality and amount of breast tissue imaged.
Abstract: The breast containing an augmentation implant presents a challenge to the mammographer and is often considered unsuitable for adequate mammographic evaluation. A modified positioning technique is described. By displacing the implant posteriorly against the chest wall and pulling breast tissue over and in front of the implant, marked improvement in compression and visualization of substantially more breast tissue is achieved. Over 250 patients with augmentation implants have been successfully studied with this modified compression technique. After review of 50 consecutive cases, two experienced mammographers confirmed a significant improvement in image quality, amount of breast tissue visualized, and overall benefit of the modified technique. Modified positioning for women with breast implants substantially improves both image quality and amount of breast tissue imaged.


Journal ArticleDOI
TL;DR: This work hypothesized that a patient who regularly became depressed each year as daylength shortened had a seasonal rhythm that, like the rhythms of other animals, was regulated by photoperiod, and hypothesized that by exposing him to bright artificial light between 0600 and 0900 hr and between 1600 and 1900 hr, this could bring him out of his winter depression, similar to what normally happened to him in the spring.

Journal ArticleDOI
TL;DR: Molecular and physiological studies of the two receptors promise to yield important new insights into the mechanisms of drug-induced psychoses, and may yield clues about the pathogenesis of endogenous psychotic disorders.

Journal ArticleDOI
TL;DR: The molecular mechanisms involved in the regulation of expression of the rat CRH gene have been examined in rat pheochromocytoma (PC-12) cells transiently transfected with a chimeric gene containing 1.4 kilobases of ratCRH 5'-flanking DNA fused to the bacterial reporter gene encoding chloramphenicol acetyltransferase.
Abstract: The molecular mechanisms involved in the regulation of expression of the rat CRH gene have been examined in rat pheochromocytoma (PC-12) cells transiently transfected with a chimeric gene containing 1.4 kilobases of rat CRH 5′-flanking DNA fused to the bacterial reporter gene encoding chloramphenicol acetyltransferase. Cyclic AMP analogs and activators of adenylate cyclase positively regulate the expression of this chimeric gene in PC-12 cells, inducing chloramphenicol acetyltransferase activity more than 15-fold. The DNA sequence required for this response to cAMP has been localized to a 59 base pair region located between 238 and 180 base pairs 5′ to the putative CRH mRNA cap site. This sequence can confer cAMP-responsiveness on a heterologous promoter in an orientation independent fashion and has homology to cAMP regulatory regions from a number of other eukaryotic genes.

Journal ArticleDOI
TL;DR: The findings indicate that cyclobenzaprine is a useful adjunct in treating patients with the fibrositis syndrome, and a significant decrease in the severity of pain and the quality of sleep is experienced.
Abstract: The efficacy of cyclobenzaprine (Flexeril), as compared with placebo, was tested in a 12-week, double-blind, controlled trial of 120 patients with fibrositis. Of the patients who received placebo, 52% dropped out due to lack of efficacy of the drug, compared with 16% of patients taking cyclobenzaprine. The dropout rate due to adverse reactions was similar in the 2 groups. Patients taking cyclobenzaprine experienced a significant decrease in the severity of pain and a significant increase in the quality of sleep. There was a trend toward improvement in the symptoms of fatigue, but morning stiffness was not alleviated. These improvements in symptoms were associated with a significant reduction in the total number of tender points and in muscle tightness. Our findings indicate that cyclobenzaprine is a useful adjunct in treating patients with the fibrositis syndrome.

Journal ArticleDOI
08 Jul 1988-Science
TL;DR: The results suggest that the inability of any particular cell line to process a prohormone precursor is due to the absence of a suitable endogenous processing enzyme.
Abstract: Mammalian cell lines (BSC-40, NG108-15, and GH4C1) that cannot process the murine neuroendocrine peptide precursor prepro-opiomelanocortin (mPOMC) when its synthesis is directed by a vaccinia virus vector were coinfected with a second recombinant vaccinia virus carrying the yeast KEX2 gene, which encodes an endopeptidase that cleaves at pairs of basic amino acid residues. mPOMC was cleaved intracellularly to a set of product peptides normally found in vivo, including mature gamma-lipotropin and beta-endorphin1-31. In GH4C1 cells (a rat pituitary line), product peptides were incorporated into stored secretory granules. These results suggest that the inability of any particular cell line to process a prohormone precursor is due to the absence of a suitable endogenous processing enzyme.

Journal ArticleDOI
TL;DR: Contaminated, reusable ventilator support equipment may be a leading cause for the extent of A. anitratus in the sputum of intubated patients and this problem is potentially correctable by the use of terminal etyhlene oxide sterilization of reusable Ventilator circuits and resuscitation bags.

Journal ArticleDOI
TL;DR: The anatomical distribution of the haloperidol-sensitive sigma receptors is distinct from the pattern of phencyclidine receptors and suggests sigma compounds may effect endocrine, emotional and motor behavior.

Journal ArticleDOI
TL;DR: The additional membrane potassium conductance that developed when agonists at mu-opioid and alpha 2-adrenoceptors were applied also became larger with membrane hyperpolarization, and this voltage dependence was also reduced or blocked by rubidium, cesium, and barium.
Abstract: Intracellular recordings were made from rat locus coeruleus neurons in vitro, and membrane currents were measured at potentials from -50 to -130 mV. In the absence of any applied agonists, the slope conductance of the cells increased 3-fold when the cell was hyperpolarized from -60 to -120 mV. This conductance increase was complete within 5 msec of the onset of a hyperpolarizing command and was subsequently independent of time for several seconds. The conductance increase was blocked by cesium chloride (1-2 mM), rubidium chloride (1-2 mM), or barium chloride (1-100 microM). The membrane potential range over which the conductance increased was centered at the potassium equilibrium potential (EK; extracellular potassium concentration, 2.5-10.5 mM): the current/voltage (I/V) relation of the cell could be well described by supposing that there were 2 potassium conductances, one voltage independent (G1) and the other (inward rectifier, Gir) activated according to the expression Gir = Gir,max/(1 + exp[(V - EK)/k]), where k ranged from 15 mV in 2.5 mM potassium to 6 mV in 10.5 mM potassium. The additional membrane potassium conductance that developed when agonists at mu-opioid and alpha 2-adrenoceptors were applied also became larger with membrane hyperpolarization, and this voltage dependence was also reduced or blocked by rubidium, cesium, and barium; in the presence of these agonists the current also reached its final value within 5 msec. However, the conductance increased by the agonists (Gag) was not well expressed by simply increasing the values of G1 and Gir,max. It was best described by a potassium conductance that increased according to Gag,max/(1 + exp[(V - Vm)/k]), where Vm (the potential at which the conductance was half-maximum) was close to the resting potential of the cell.(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
TL;DR: The kinetics of change in the extent of hyperactivation and in acrosomal loss, although measured in different cell populations, are consistent with an association between these two events.
Abstract: The occurrence and time course of capacitation, acrosomal loss, and hyperactivated motility require quantitative definition in order to characterize fertile human sperm. In this study, video microscopy and digital image analysis were used to measure curvilinear (VCL) and straight line (VSL) velocity, average linearity of progression (UN [100 x VSL/VCUJ), maximum and mean amplitude of lateral head displacement (ALH), beat-cross-frequency (BCF), DANCE (VCL x meanALH) and DANCEMEAN (meanALH/(UIN/100)). These parameters were measured for sperm in semen and in the swim-up fraction of washed cells during incubation for up to 24 h under in vitro fertilization (IVF) conditions. Acrosomal loss was monitored in the same population of washed cells by an immunofluorescence end-point assay. The greatest increase in mean values of motility parameters was observed when seminal sperm were washed free of seminal plasma. Increases continued for up to 6 h of incubation. Two subpopulations of hyperactivated sperm were identified; one type, not found in semen, showed star-spin trajectories, and constituted 3.0, 3.8, 4.5, and 4.1% of the swim-up population after 0, 3, 6 and 24 h of incubation. The second type, termed transitional showed a more progressive trajectory and constituted less than 1% in semen. In total, hyperactivated cells constituted 0.8% of cells in semen, 14.5% of the swim-up population with no incubation, and 23.1, 22.7, and 19.4% after 3, 6, and 24 h of incubation, respectively. Acrosomal loss in the swim-up population was delayed during the first 3 h of incubation, then increased from near 5% at 3 h to 7 and 12% at 6 and 24 h, respectively. The kinetics of change in the extent of hyperactivation and in acrosomal loss, although measured in different cell populations, are consistent with an association between these two events.

Journal ArticleDOI
TL;DR: The hearing of 24 patients was tested before and after MR imaging, and the noise generated by MR imagers may cause temporary hearing loss, and earplugs can prevent this loss.
Abstract: To determine if the loud noise generated by magnetic resonance (MR) imaging equipment is capable of inducing hearing loss, the hearing of 24 patients was tested before and after MR imaging. Fourteen patients were imaged without ear protection, and six (43%) suffered a temporary, mild loss of hearing (less than or equal to 15 dB at at least one frequency). Ten patients were imaged with ear protection, and only one experienced any hearing loss. Therefore, the noise generated by MR imagers may cause temporary hearing loss, and earplugs can prevent this loss. All threshold changes had returned to within 10 dB of baseline by 15 minutes after completion of the second audiometric test.

Journal Article
TL;DR: Observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1.
Abstract: Many of the pathophysiologic effects of bacterial endotoxin have recently been attributed to a monokine, tumor necrosis factor (TNF). The rabbit eye is extremely sensitive to locally injected endotoxin. The authors have investigated the possible contribution of TNF to ocular inflammation in a rabbit model. The intravitreal injection of 10(5) to 5 X 10(5) units of recombinant human TNF produced a sustained disruption of the blood-aqueous barrier as manifested by elevated aqueous humor protein levels. In addition, 83% of rabbits receiving this dose of TNF developed hyperemia of limbal vessels and early neovascularization of the cornea. Many developed posterior synechiae (fibrous adhesions between the iris and the lens). TNF induced only a slight cellular response in the anterior chamber. Histologic studies confirmed the presence of new vessels and demonstrated a marked mononuclear infiltrate within and beneath the epithelium of the iris and ciliary body. Lower doses of TNF produced inconsistent results. Heating TNF completely destroyed its inflammatory effects. The time course of the ocular response to TNF and the quantity of recombinant protein needed to produce consistent effects were vastly different from effects observed with interleukin-1. For example, 24 hours after an intravitreal injection, 2.2 X 10(4) ng of TNF (5 X 10(5) units) produced significantly less protein extravasation and polymorphonuclear leukocyte infiltration than 4 ng of recombinant interleukin-1. Similarly, 24 hours after intravitreal injection, 1 ng of Escherichia coli endotoxin tended to be a more potent inflammatory stimulus than this quantity of TNF. These observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1.