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Biomedical subjects

L R Johnson

Publications and source records attributed to L R Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effects of smoking and smoking cessation on longitudinal decline in pulmonary function.

Effects of cigarette smoking and smoking cessation on rate of FEV1 decline over 6 yr were examined in 4,451 Japanese-American men from the Honolulu Heart Program who were 45 to 68 yr of age at baseline (1965-1968). Within-person regression was used to calculate annual change in FEV1. Rates of FEV1 decline varied strongly with smoking status and increased significantly with age. Overall, men who continued to smoke experienced steeper rates of decline compared with men who never smoked (-33 ml/yr versus -22 ml/yr, respectively; p = 0.0001). Rates of decline for those who quit smoking during the first 2 yr (-32 ml/yr) were nearly the same as those who continued smoking (-34 ml/yr). After quitting, their rates of decline diminished to a level (-19 ml/yr) similar to that of men who had never smoked (-21 ml/yr). FEV1 decline in continuing smokers was significantly associated with duration of smoking, whereas associations with intensity and pack-years were of borderline significance. Among 216 men with impaired pulmonary function, those who quit smoking had significantly slower rates of FEV1 decline than did those who continued smoking. Potential reasons for quitting included respiratory conditions and stroke. These results extend previous reports of accelerated rates of FEV1 decline in the persons who continue to smoke, and they indicate that smoking cessation leads to less steep rates of decline in pulmonary function over a short period of time in middle-aged men, as well as in men with established pulmonary impairment.

Aging↗
PubMed1995

Structural requirements of analogues of polyamines for migration and growth of IEC-6 cells.

Healing of gastrointestinal mucosal lesions occurs through two processes: an early one involving cell migration and a later one in which cell division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown. In the present study, we examined the ability of analogues of spermidine and spermine to support migration and growth of IEC-6 cells that have been grown in alpha-difluoromethylornithine to inhibit polyamines. All analogues of spermidine with the general formula x-3 (referring to the numbers of carbon atoms on either side of the central nitrogen), where x = 2-12, competed with spermidine for entry into the cells. However, in addition to spermidine (x = 4), only compounds for which x = 2, 3, or 6 supported migration and only those for which x = 2 or 7 supported growth. Spermine analogues 3-x-3, for which x = 3, 6, 9, or 12, competed for entry into the cells, but only compounds for which x = 3 or 6 supported migration and only the compound for which x = 3, in addition to spermine (x = 4), supported growth. In addition, analogues 2-3-2, 3-2-3, and 2-(3)2, a branched compound, supported both migration and growth but entered the cell via a mechanism different than that for spermidine and spermine. These data define some of the specific structural requirements for polyamines to produce their physiological effects.

Animals↗
PubMed1995

Inhibition of ornithine decarboxylase activity but not expression of the gene by cimetidine in intestinal mucosal cells.

Cimetidine has been shown to inhibit normal and carcinoma cell growth but the mechanism of the antiproliferative action is incompletely understood. The current study determined the influence of cimetidine on ornithine decarboxylase (ODC) activity, which is the initial rate-limiting enzyme in polyamine biosynthesis, in rat duodenal mucosa and IEC-6 cells (a line of normal rat intestinal crypt cells). Rats were fasted 22 hr before the various treatments and ODC activity was measured in scraped duodenal mucosa. Administration of pentagastrin and epidermal growth factor (EGF) and refeeding fasted rats significantly increased ODC activity in duodenal mucosa. Cimetidine completely inhibited increases in ODC activity in the mucosa stimulated by pentagastrin and EGF, but not by refeeding. Ranitidine and H1-receptor antagonist chlorpheniramine had similar inhibitory effects on ODC activity induced by gastrin. In cultured IEC-6 cells, cimetidine caused a linear and significant inhibition of the stimulation of ODC activity in response to pentagastrin, EGF, 5% dialyzed fetal bovine serum (FBS) and asparagine. ODC messenger RNA (mRNA) levels in IEC-6 cells were significantly increased after exposure to 5% dialyzed FBS and asparagine. Although cimetidine almost completely prevented the induction of ODC activity in IEC-6 cells exposed to serum or asparagine, the increases in ODC mRNA levels were not inhibited by the compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Phototoxicology. 1. Light-enhanced toxicity of TNT and some related compounds to Daphnia magna and Lytechinus variagatus embryos.

Many environmental pollutants interact with solar near-ultraviolet (nuv) light in a manner which greatly increases their toxic effects. The phenomenon of light-mediated toxicity (phototoxicity) is only now becoming generally recognized to any significant degree. Manufacture of, and loading munitions with, the explosive 2,4,6-trinitrotoluene (TNT) in past decades caused contamination of soils and sediments at levels exceeding 1000 ppm and of waters at levels near saturation (100 ppm). Manufacture of TNT produces numerous nitrated by-products, and most of these compounds, including TNT, can be metabolized by many species, including bacteria, fungi, plants, and mammals. This study investigated the phototoxicity of TNT, and 2,3-, 2,4-, 2,6-, and 3,4-dinitrotoluene (DNT) and -diaminotoluene (DAT), and the major metabolites 2-amino-4,6-dinitrotoluene (2A) and 4-amino-2,6-dinitrotoluene (4A), to Daphnia magna (acute toxicity) and Lytechinus variagatus (sea urchin) embryos (subacute, developmental toxicity). Most of the compounds were weakly toxic or nontoxic in the dark. All were phototoxic to sea urchins. In D. magna, 2,3- and 3,4-DNT/DAT and 4A were not toxic but were phototoxic, and 2A was toxic and phototoxic; the other isomers were not toxic or phototoxic to this species.

Animals↗
PubMed1994

Phototoxicology. 2. Near-ultraviolet light enhancement of Microtox assays of trinitrotoluene and aminodinitrotoluenes.

Coexposure of 2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2A), or 4-amino-2,6-dinitrotoluene (4A) to near-ultraviolet (nuv) light (lambda max-354 nm) significantly enhanced their toxicity toward Photobacterium phosphoreum (Microtox bioassay) during 30 min but not 15 min. Based on the slopes of the dose-response lines, the nuv coexposure and dark toxic mechanisms of action for TNT, 2A, and 4A appeared to be similar. nuv coexposure of binary mixtures significantly enhanced (supraadditivity) the toxicity of these compounds to P. phosphoreum. Under normal laboratory lighting, the toxicity of TNT + 2A and 2A + 4A mixtures were supraadditive but the toxicity of TNT + 4A mixtures could be explained by simple addition. Supporting these conclusions, the response curves of alpha-terthienyl, a compound known not to require nuv for toxicity, were similar in the dark and with nuv coexposure. In contrast, angelicin and psoralen, compounds known to require nuv coexposure to damage DNA, gave response curves having different slopes in the dark and with nuv coexposure. The nuv coexposure Microtox assay was able to detect and quantify phototoxicity in psoralen, angelicin, alpha-terthienyl, anthracene, TNT, and aminodinitrotoluenes.

Aniline Compounds↗
PubMed1994

Phototoxicology. 3. Comparative toxicity of trinitrotoluene and aminodinitrotoluenes to Daphnia magna, Dugesia dorotocephala, and sheep erythrocytes.

2,4,6-Trinitrotoluene (TNT) and compounds associated with its production are toxic and phototoxic to a wide range of biota. The planarian Dugesia dorotocephala, but not Daphnia magna, metabolized TNT (1 mg/liter) to 4-amino-2,6-dinitrotoluene (4A; 0.4 mg/liter) and 2-amino-4,6-dinitrotoluene (2A; 0.2 mg/liter). Coexposure to near-ultraviolet (nuv) light enhanced the toxicity of 2A more than that of TNT and 4A. The toxicities of TNT, 4A, and 2A to Du. dorotocephala were all decreased by glutathione (GSH) conjugation. This suggests that all had mechanisms of toxic action involving formation of quinone-GSH conjugates. Dark and light mechanisms for TNT and 2A depended on GSH conjugation, but the specific mechanisms may be different for each compound. The dark and light mechanisms of toxic action for 4A appeared to be fundamentally different in that the dark toxic mechanism of action was less dependent on GSH conjugation. Hemolysis studies using sheep erythrocytes showed that the light-enhanced toxic mechanism of action for TNT, 2A, and/or 4A did not involve cellular membrane damage in response to nuv-induced anions.

Abnormalities, Drug-Induced↗
PubMed1994

Input from the amygdala to the rat nucleus accumbens: its relationship with tyrosine hydroxylase immunoreactivity and identified neurons.

Both tyrosine hydroxylase-positive fibres from the mesolimbic dopamine system and amygdala projection fibres from the basolateral nucleus are known to terminate heavily in the nucleus accumbens. Caudal amygdala fibres travelling dorsally via the stria terminalis project densely to the nucleus accumbens shell, especially in the dopamine rich septal hook. The amygdala has been associated with the recognition of emotionally relevant stimuli while the mesolimbic dopamine system is implicated with reward mechanisms. There is behavioural and electrophysiological evidence that the amygdala input to the nucleus accumbens is modulated by the mesolimbic dopamine input, but it is not known how these pathways interact anatomically within the nucleus accumbens. Using a variety of neuroanatomical techniques including anterograde and retrograde tracing, immunocytochemistry and intracellular filling, we have demonstrated convergence of these inputs on to medium-sized spiny neurons. The terminals of the basolateral amygdala projection make asymmetrical synapses predominantly on the heads of spines which also receive on their necks or adjacent dendrites, symmetrical synaptic input from the mesolimbic dopamine system. Some of these neurons have also been identified as projection neurons, possibly to the ventral pallidum. We have shown a synaptic level how dopamine is positioned to modulate excitatory limbic input in the nucleus accumbens.

Amygdala↗
PubMed1994

Polyamines influence transglutaminase activity and cell migration in two cell lines.

Transglutaminases (TGAs) catalyze the cross-linking of proteins through formation of gamma-glutaminyl-epsilon-lysine bonds and incorporation of small-molecular-weight amines, including polyamines, into the gamma-glutamine sites of proteins. Tissue TGA has been shown to establish covalent cross-links between cytoskeletal proteins using polyamines as substrates, and protein-polyamine conjugates have been identified in a variety of cells. We have shown previously that polyamines are required for cell migration in IEC-6 cells [S. A. McCormack, M. J. Viar, and L. R. Johnson. Am. J. Physiol. 264 (Gastrointest. Liver Physiol. 27): G367-G374, 1993]. In this study, we explored the relationship between cell migration, polyamines, and tissue TGA activity in two cell lines and found that while both IEC-6 and Caco-2 cells required normal levels of polyamines to migrate across a denuded surface, tissue TGA activity responded differently to polyamine deficiency brought about by treatment with alpha-difluoromethylornithine (DFMO). DFMO is a specific and irreversible inhibitor of ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis. In IEC-6 cells, tissue TGA activity decreased significantly with DFMO treatment concurrent with a rise in inactive TGA protein as measured by Western blot analysis. On the other hand, in Caco-2 cells, tissue TGA activity and protein increased significantly with DFMO treatment. In both cell lines, addition of polyamines to the DFMO treatment restored cell migration, tissue TGA activity, and protein to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Polyamine deficiency causes reorganization of F-actin and tropomyosin in IEC-6 cells.

In earlier work we have shown that polyamine-deficient IEC-6 cells lose most of their ability to migrate. In this report we describe the effect of polyamine deficiency on the cytoskeleton of migrating IEC-6 cells. Cells were grown on cover slips for 4 days. One-third of the monolayer was removed, and the remainder was incubated for 6 h. The monolayers were fixed and stained with rhodamine phalloidin for actin filaments and by immunocytochemistry for tropomyosin. In control cells, actin filaments were found as stress fibers traversing the cell, in a thin actin cortex often visible on only one edge of the cell, and in fine fibers extending into the lamellipodia. Tropomyosin was found in the same distribution. A Western blot showed that tropomyosin was present as 35- and 37-kDa isoforms. In polyamine-deficient cells, actin stress fibers were less dense, whereas the actin cortex was greatly increased in density and lamellipodia were less extensive. Tropomyosin distribution was similar and included a 30-kDa isoform not seen previously. In spite of the obvious changes in the distribution of these cytoskeletal proteins, the concentrations of filamentous actin, beta-actin mRNA, and the higher molecular weight tropomyosin isoforms did not change. In all cases the addition of putrescine to polyamine-deficient cells prevented the changes described. We conclude that polyamines are essential for migration in this system because of their effects on the organization of cytoskeletal actin, tropomyosin, and perhaps other proteins as well.

Actins↗
PubMed1994

Expression of protooncogenes c-fos and c-myc in healing of gastric mucosal stress ulcers.

The current study determines the hypothesis that expression of protooncogenes c-fos and c-myc is involved in the mechanism of polyamine-stimulated healing in gastric mucosal stress ulcers. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 2-6 h. Animals were killed either immediately after stress or at 2-h intervals up to 24 h after 6 h of stress. Stress caused both visible lesions and induction of ornithine decarboxylase (ODC) activity in the oxyntic gland mucosa after 2 h. Increased ODC activity was paralleled by increases in the mucosal polyamines putrescine, spermidine, and spermine. Exposure to stress led to appearance of c-fos mRNA and oncoprotein in the gastric oxyntic gland mucosa at 2 h and its disappearance by 4 h. Baseline expression of c-myc was enhanced significantly after 6 h of stress and remained elevated for 4 h. This change in the expression of c-fos and c-myc mRNA and oncoprotein preceded an increased rate of [3H]thymidine incorporation into mucosal DNA. Administration of alpha-difluoromethylornithine (DFMO, 500 mg/kg ip) totally prevented the marked increases in ODC activity and polyamine levels. DFMO also completely inhibited the expression of c-fos and significantly decreased c-myc mRNA and oncoprotein in the gastric mucosa of stressed rats. The healing process, which was significant by 12 h, was markedly inhibited by DFMO. These results show that 1) mucosa exposed to stress exhibits increased expression of c-fos and c-myc following increased polyamine synthesis and 2) inhibition of polyamine biosynthesis by DFMO decreases both protooncogene expression and mucosal healing.

Animals↗
PubMed1994

Secretin inhibits induction of ornithine decarboxylase activity by gastrin in duodenal mucosa and IEC-6 cells.

Ornithine decarboxylase (ODC) catalyzes the first rate-limiting step in polyamine biosynthesis, and increased ODC activity is one of the earliest biochemical events associated with the induction of cellular proliferation. The current study examines the regulation of ODC activity in rat duodenal mucosa and IEC-6 cells (a line of normal rat intestinal crypt cells) in response to the trophic hormone, gastrin, and its inhibitor, secretin. Rats were fasted 22 h before the various treatments, and ODC activity was measured in scraped duodenal mucosa. Gastrin significantly increased ODC activity within 3 h to 4.3 times control levels. The effect of gastrin was totally inhibited by 5 micrograms/kg secretin. In doses of 5 or 10 micrograms/kg, secretin had no effect on basal ODC. Epidermal growth factor (EGF) and refeeding fasted rats also significantly increased ODC activity in duodenal mucosa, but the effects of EGF and refeeding were not prevented by secretin. In cultured IEC-6 cells, ODC activity was significantly increased after exposure to gastrin, 5% dialyzed fetal bovine serum (FBS), EGF, and asparagine. Secretin in doses ranging from 10(-10) to 10(-6) M caused a linear and significant inhibition of the stimulation of ODC activity by gastrin. No dose of secretin affected basal ODC activity or enzyme activity stimulated by 5% dialyzed FBS, EGF, or asparagine in IEC-6 cells. The ODC mRNA levels in IEC-6 cells were also increased after exposure to gastrin. Administration of secretin significantly prevented the stimulated expression of the ODC gene in cells treated with gastrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Volume spirometers need automated internal temperature sensors.

Spirometer temperature was measured automatically during all years of the Lung Health Study. Short- and long-term changes in temperature were analyzed for the 23 dry-rolling-seal volume spirometers used at the 10 clinical centers involved in the study. Within-test-session spirometer temperature increased a mean of 0.3 degrees C, and as much as 3.0 degrees C during methacholine challenge testing. The maximal change in spirometer temperature during a test day exceeded 4 degrees C more than 5% of the time. Month-to-month changes of more than 15 degrees C were not uncommon. If ambient temperature had been assumed to apply to all maneuvers and used for BTPS corrections, FEV1, and FVC measurement errors of up to 6% would have occurred. When using volume spirometers, the temperature of air inside the spirometer should be measured accurately during each breathing maneuver.

Bronchial Provocation Tests↗
PubMed1994

Regulation of transglutaminase activity by polyamines in the gastrointestinal mucosa of rats.

Transglutaminases catalyze the covalent cross-linking of protein and are involved in the mechanism of polyamine-dependent mucosal healing. The current study examined the effect of polyamines on transglutaminase activity in gastrointestinal mucosa. Rats were fasted 22 hr before experiments and enzyme activity was measured as the Ca(++)-dependent covalent incorporation of [3H]-putrescine into acid-precipitable protein. In some of the experiments, mucosal ornithine decarboxylase (ODC) activity and polyamine levels were also examined. Transglutaminase activity in both gastric and duodenal mucosa increased significantly after polyamine administration. Treatment with alpha-difluoromethylornithine (DFMO) decreased both basal ODC activity and putrescine levels in the duodenal mucosa. DFMO also significantly decreased mucosal transglutaminase activity. In stress or hypertonic NaCl-induced gastric mucosal injury models, increased polyamine biosynthesis was associated with increased transglutaminase activity, which was completely prevented by DFMO. Exogenous polyamines returned transglutaminase activity toward control levels in the presence of DFMO. In conclusion, these results indicate that: (i) luminal polyamines increase transglutaminase activity in gastric and duodenal mucosa; (ii) polyamine depletion caused by the inhibition of ODC is accompanied by a significant decrease in transglutaminase activity; and (iii) exogenous polyamines significantly reverse the decrease in transglutaminase activity caused by polyamine depletion.

Animals↗
PubMed1994

Cultivating expertise in oncology nursing: methods, mentors, and memories.

PURPOSE: To explore the development of clinical expertise and the role of mentoring experiences in this process for oncology nurses involved in direct patient care. DESIGN: Multi-institutional, descriptive, qualitative. SETTING: Six sites in different regions of the United States; rural and urban cancer and noncancer centers. SAMPLE: 38 oncology nurses (mean age = 35 years; average time in nursing = 10 years and in oncology = 7 years; 47% bachelor of science in nursing, 29% diploma, 13% associate degree in nursing, and 11% master's prepared). METHODS: Phenomenological; content analysis of interviews. FINDINGS: Development of clinical expertise and professional commitment requires a combination of protégée- and mentor-initiated behaviors. Protégée learning included reading, watching, attending, doing, asking questions, seeking peer support, seeking new opportunities, and associating with others. Mentor contributions included modeling standards and beliefs, coping effectively, explaining knowledge, and believing in, challenging, and supporting the protégée personally and professionally. The absence of mentoring also was of concern to nurses. True mentoring required on interpersonal connection and commitment between the protégée and mentor. IMPLICATIONS FOR NURSING PRACTICE: Mentoring enhances the development of expert nurses who combine competent clinical practice with strong interpersonal commitment to their patients and the oncology nursing profession. The benefits of mentoring outcomes for individual oncology nurses, their patients, the institutional setting, and the profession need further exploration, especially given the focus on advanced practice and healthcare reform.

Adult↗
PubMed1993

Surgical management of atypical lateral tracheal collapse in a dog.

Tracheal collapse is often diagnosed in small-breed dogs through use of conventional radiography or fluoroscopy, by which the dorsoventral orientation of the collapse can be seen. In the dog of this report, an unusual lateral form of tracheal collapse was diagnosed by means of bronchoscopy after multiple radiographic procedures had failed to define a cause for cough and dyspnea. Surgical reinforcement of the abnormal region of the trachea resulted in resolution of clinical signs and in reduction in dynamic airway collapse, which was documented on follow-up bronchoscopy.

Animals↗
PubMed1993

Nerve growth factor receptor (p75)-immunoreactivity in the normal adult feline trigeminal system and following retrogasserian rhizotomy.

The 75 kDa protein nerve growth factor receptor [NGFr(p75)] is a neurotrophin receptor that is able to bind different members of the neurotrophin family of molecules implicated in affecting neuronal survival. Here we describe the light microscopic distribution of NGFr(p75)-immunoreactivity (IR) within the feline trigeminal brainstem sensory nuclear complex and trigeminal ganglion of normal adult subjects and in subjects 10 and 30 days following retrogasserian rhizotomy. Within the trigeminal ganglion of normal subjects, numerous fibers and most of the neuronal cell bodies showed NGFr(p75)-IR that varied in intensity, while cells and fibers with NGFr(p75)-IR were less numerous within the mesencephalic trigeminal nucleus. Within the main sensory and spinal trigeminal nuclei, NGFr(p75)-IR formed a reproducible pattern that varied between the different subnuclei. The NGFr(p75)-IR consisted both of dense pockets and a low level NGFr(p75)-IR that was selective to the trigeminal neuropil. Following rhizotomy, most of the NGFr(p75)-IR was lost from the main sensory and spinal trigeminal nuclei, except in regions where the upper cervical roots and cranial nerves VII, IX, and X project. In contrast, examination of the central root that was still attached to the trigeminal ganglion showed increased NGFr(p75)-IR in fibers and supporting cells, as did the motor root within the peripheral mandibular division. These results indicate that the majority of the NGFr(p75)-IR within the main sensory and spinal trigeminal nuclei originates from primary trigeminal afferents and that retrogasserian rhizotomy leads to an up-regulation of NGFr(p75)-IR in the part of the central root that is contiguous with the ganglion.

Animals↗
PubMed1993

t haplotypes in the mouse compromise sperm flagellar function.

The t haplotypes are variant forms of the proximal portion of chromosome 17 in the mouse. The t haplotypes alter spermatogenesis and many also contain lethal factors. Although the lethal factors vary between t haplotypes, all t haplotypes have the same effect on sperm, that of altering sperm function in fertilization. It is not clear, however, whether the nature of the sperm dysfunction is the same in all t haplotypes. Studies to date have focused on only one or two aspects of sperm function or have not examined sperm from males carrying different t haplotypes. In addition, factors within the t haplotypes interact with the genetic background, so that comparisons to sperm from t/+ or +/+ mice having different alleles at loci outside the t haplotypes may not be valid. To determine the nature of the sperm dysfunction caused by the t haplotypes, we have studied sperm from mice of the same genetic strain carrying none, one, or two t haplotypes. Sperm from tw32/+, tw5/+, and tw32/tw5 mice exhibited premature hyperactivation, a type of vigorous but nonprogressive motility correlated with fertility, while their rates of capacitation (the ability to undergo the acrosome reaction in response to zona proteins) and spontaneous acrosome reaction were similar to those of wild-type sperm. In addition, sperm flagellar curvature was abnormal: flagella from heterozygotes had an acute bend in the midpiece, giving the sperm a "fishhook" appearance, while the entire flagellum of sperm from tw32/tw5 mice was curled. Also, fewer sperm from tw32/tw5 mice were initially motile. Since all of these motility defects were dependent on exogenous calcium, the t haplotypes could specify an abnormal, calcium-sensitive component of the flagellum. The motility defects could also contribute to the dysfunction of these sperm by inhibiting their passage to the site of fertilization in vivo.

Acrosome↗