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Biomedical subjects

L R Johnson

Publications and source records attributed to L R Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1989

Induction of gastric and duodenal mucosal ornithine decarboxylase during stress.

The purpose of this study was to determine whether gastric and duodenal mucosal ornithine decarboxylase (ODC) activity increased during a period of ulcer-producing stress and whether changes in enzyme activity altered the severity of damage. Rats were fasted for 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for different times lasting from 2 to 8 h. After 6 h, stress slightly increased gastric mucosal ODC and caused a sevenfold increase in duodenal mucosal ODC activity. Macroscopic ulcers developed in the oxyntic gland mucosa but not duodenal mucosa. Interestingly, however, after 6 h microscopic inspection showed an absence of most villi from the duodenum. DNA, RNA, and protein content of both tissues decreased over the time rats were exposed to stress. DL-alpha-Difluoromethylornithine (DFMO, a specific ODC inhibitor) prevented the increase in ODC in both tissues and increased the loss of DNA and RNA from duodenal mucosa. The degree of damage was not altered by DFMO in either tissue in response to 6 h of stress. These results show that 1) stress causes microscopic damage to the duodenum, 2) stress increases ODC in both gastric and duodenal mucosa, and 3) the inhibition of ODC during 6 h of stress does not alter the severity of damage.

Animals↗
PubMed1988

Longitudinal versus cross-sectional estimation of lung function decline--further insights.

This paper explores the extent to which differences in longitudinal versus cross-sectional inference may be influenced by the choice of statistical models. Using lung function data on 524 working men, we first compare the goodness-of-fit and implication for longitudinal decline of a variety of cross-sectional models. We then compare the predicted longitudinal patterns from these models with those observed over a period of four years. In general, both approaches provide qualitatively, if not quantitatively, similar messages concerning the relative effects of smoking and age on lung function decline. Nonetheless, we acknowledge the existence of real selection and cohort effects. Although we recognize the utility of cross-sectional designs, we discourage quantitative comparisons between studies, especially longitudinal versus cross-sectional.

Adult↗
PubMed1988

Characteristics of putrescine uptake in isolated rat enterocytes.

Polyamines are necessary for the growth of eukaryotic cells and are supplied either by new synthesis or cellular uptake. To our knowledge, no information is available on polyamine uptake by gastrointestinal cells. In the current study, isolated villous enterocytes from the rat accumulated putrescine to an eightfold concentration gradient. Uptake was temperature dependent, saturable, and inhibited by 1 mM KCN. Kinetic analysis showed a Km of 1.23 X 10(-5) M and a Vmax of 2.60 X 10(-10) mol.10(6) cells-1.15 min-1. Enterocytes from the distal one-fourth of the gut showed the highest rate of uptake. Putrescine uptake was inhibited by cadaverine and spermine but not by the amino acids asparagine, AIB, or leucine. Sodium replacement by choline, lithium, N-methyl-D-glucamine, or tetramethylammonium significantly inhibited uptake, but replacement of Na+ by sucrose or mannitol was without effect. The inhibition observed was believed to be due to the ability of the cations to interact in some way with the carrier. Neither ouabain nor digitoxigenin had any effect on uptake. These data indicate that putrescine is accumulated by villous enterocytes by a carrier-mediated process that does not appear to involve Na+ contransport.

Animals↗
PubMed1988

Amiloride inhibits rat mucosal ornithine decarboxylase activity and DNA synthesis.

Refeeding fasted rats induces a dramatic trophic response in gastrointestinal mucosa and is associated with elevations in both the rate of DNA synthesis and ornithine decarboxylase (ODC) activity. The signal for these increases is unknown. Amiloride prevents cell alkalinization by blocking Na+-H+ exchange at apical epithelial cell membranes. In study 1, rats were fasted 48 h, treated with amiloride (0.5 to 500 mg/kg), and refed for 4 h. Refeeding increased ODC activities in the jejunal mucosa (X8) and liver (X19) but not in the oxyntic gland mucosa. In the jejunum, but not the liver, the activation of ODC was completely abolished by 100 mg/kg amiloride. In study 2, the rate of DNA synthesis was determined by measuring the rate of [3H]thymidine incorporation 16 h after refeeding. Refeeding resulted in significantly increased rates of DNA synthesis (dpm.microgram DNA-1.30 min-1) over fasted levels, and amiloride at 100 mg/kg significantly reduced the elevations in the jejunum and liver. In conclusion, amiloride inhibits the postprandial increases in jejunal ODC activity and DNA synthesis in the jejunum and liver. The results indicate that 1) the Na+-H+ antiport is essential to the increased ODC activity in the jejunum and the stimulation of DNA synthesis in the jejunum and liver after a meal and 2) increases in DNA synthesis and their suppression by amiloride are not necessarily linked to ODC activity.

Amiloride↗
PubMed1988

Gastric mucosal ornithine decarboxylase: localization and stimulation by gastrin.

Gastrin injection and refeeding fasted rats are effective trophic stimuli for the oxyntic gland mucosa of the stomach. Neither stimulus increases detectable ornithine decarboxylase (ODC) activity in the tissue. Difluoromethylornithine (DFMO), a potent inhibitor of ODC, blocks the mucosal growth response, indicating that ODC activity is necessary for growth. Elevated levels of spermidine and spermine are detectable in the mucosa after gastrin administration. Using a highly specific, polyclonal antiserum to ODC, we determined that the enzyme is present in oxyntic gland mucosa confined to a narrow band of cells at the base of the gastric pits and openings of the glands. In antral mucosa, ODC is present throughout the lower 20% of the mucosa, which consists of the necks and pyloric glands. Using antiserum dilution techniques, we show that gastrin administration increases immunoreactive ODC in the oxyntic gland area but not in the antral mucosa, where it has no trophic effect. Elevated cellular content of ODC is apparent within 2 h after injection of gastrin, peaks at 4 h, and declines to basal levels by 12 h. Gastrin-stimulated increase in ODC is confined to the narrow band of cells in which low levels of the enzyme protein were detected in control animals. The decarboxylating activity detectable in oxyntic gland mucosal extracts is not inhibited by administration of DFMO or cycloheximide, each of which inhibits ODC activity in other tissues. Addition of unlabeled lysine to the decarboxylation assay reaction of oxyntic gland mucosa extract inhibits the decarboxylation of radiolabeled ornithine substrate. Thus it is likely that the stomach possesses nonspecific decarboxylase activity, which accounts for most of the measured activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Does the single-breath N2 test identify the smoker who will develop chronic airflow limitation?

We report here the results of a 9- to 11-yr follow-up of 2 cohorts in which spirometry and the single-breath N2 test were used throughout the follow-up period to determine the usefulness of the single-breath N2 test in identifying the smoker who is experiencing a rapid decline in FEV1 and is therefore likely to be at risk of developing chronic airflow limitation. The analyses are based on 734 subjects tested from 3 to 5 times over the follow-up period; 82 smokers developed an abnormal FEV1 during the follow-up period. Of these, 71 (87%) had had an abnormal single-breath N2 test at some time prior to the FEV1 becoming abnormal. Of the single-breath N2 test variables, CC/TLC was the only one significantly associated with the rate of decline of FEV1 in both cohorts once adjustments were made for age, sex, height, and smoking. We conclude that the single-breath N2 test can be useful in identifying the smoker who is at risk of developing chronic airflow limitation. However, its usefulness is diminished by the high proportion of smokers who have mild functional abnormalities but do not progress to develop chronic airflow limitation. We also find that the single-breath N2 test does not appear to have a useful predictive value in nonsmokers.

Adult↗
PubMed1988

Reference values for FEV1 in Japanese-American men from 45 to 68 years of age.

Pulmonary function is known to vary by racial group, yet no standards have been published for Asian-Americans. The Honolulu Heart Program, a prospective epidemiologic study of cardiovascular disease, provided an opportunity to examine pulmonary function, specifically, forced expiratory volume in one second (FEV1), in Japanese-American men 45 to 68 yr of age. Of a cohort of 6,346 men, 1,490 were identified as healthy asymptomatic nonsmokers. Prediction equations and reference values were derived from this subgroup. When the prediction equation was compared with those derived from Caucasian and black populations, mean predicted FEV1 for Japanese-Americans was intermediate to higher values for Caucasians and lower values for blacks. In addition to age and height, skinfolds, dynamometry, and biacromial diameter were found to be independent predictors of FEV1. In summary, standards derived from Japanese-American populations should be used when measuring pulmonary function in this group and additional physical measurements make a small contribution to the accuracy of prediction equations.

Aged↗
PubMed1988

Correlates of FEV1 and prevalence of pulmonary conditions in Japanese-American men.

Correlates of forced expiratory volume in one second (FEV1) and the prevalence of pulmonary disease and symptoms were examined in 6,346 Japanese-American men 45 to 68 yr of age. There was a significant inverse dose-response relationship between FEV1 and cigarette smoking measured as pack-years, number of cigarettes, or number of years smoked. Ex-smokers had FEV1 values that were intermediate to the higher values for nonsmokers and the lower values for current smokers. Among current smokers, inhaling and starting to smoke at a younger age were associated with lower values of FEV1, independent of pack-years. FEV1 was also correlated with a variety of other biologic and sociobehavioral variables, even after removing the effects of smoking. These variables included skinfold thickness, dynamometry, hematocrit, triglycerides, and systolic blood pressure. When compared with Caucasian populations, these Japanese-American men had low prevalence rates of airflow obstruction and pulmonary disease symptoms.

Aged↗
PubMed1988

Prostaglandin-mediated trophic effects on the rat duodenum: the role of polyamines.

Ornithine decarboxylase (ODC) is the initial rate-limiting enzyme in polyamine biosynthesis. The relationship between ODC and polyamines and the trophic effect of prostaglandin in the rat gastrointestinal tract are unknown. In these studies we determined whether inhibition of ODC activity and subsequent polyamine biosynthesis with the specific enzyme inhibitor difluoromethyornithine (DFMO) would attenuate prostaglandin-mediated trophic effects in the rat duodenum. Significant increases in duodenal mucosal wet weight, RNA, DNA, and protein were found following treatment with 16,16-dimethyl-PGE2 (1 mg/kg) for 1 week. This trophic response was significantly reduced (P less than 0.01) in the duodenum of rats treated concomitantly with DFMO. In addition, this prostenoid significantly increased (4X) duodenal ODC levels, 2 hr following acute administration. These results suggest that polyamines are required for the prostaglandin-stimulated growth of the rat duodenal mucosa.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Effect of putrescine on oxyntic gland and colonic mucosal growth in rats.

The effect of putrescine on oxyntic gland and colonic mucosal growth was studied by measuring the rate of [3H]-thymidine incorporation into mucosal DNA in vitro (DNA synthesis) and DNA, RNA and protein content of the mucosa following intramuscular injections of the compound (50 mumoles/100g). Saline injected animals served as controls. Multiple injections of putrescine during a 2-day fast produced a significant enhancement of mucosal DNA synthesis in oxyntic gland and colonic mucosa, with no apparent change in DNA, RNA or protein content in either of the tissues, compared to the corresponding saline-controls, when measurements were made 12-24 h after the last injection. However, when the animals were killed after 4 days, DNA, RNA and protein content of oxyntic gland mucosa, and DNA and protein content of colonic mucosa were found to be significantly higher than in the respective saline-controls. We conclude that putrescine, taken up from the blood, can stimulate growth of gastrointestinal mucosa.

Animals↗
PubMed1987

Ultrastructure of degenerative changes following ricin application to feline dental pulps.

The ultrastructure of degenerative changes within the ipsilateral trigeminal ganglion, and partes caudalis and interpolaris of the spinal trigeminal nucleus in the cat is described following the application of the potent toxin ricin to the tooth pulps of unilateral maxillary and mandibular posterior teeth, including the cuspids. Survival times ranged from 6 to 10 days. Typical changes identified within the ipsilateral trigeminal ganglion included myelin fragmentation and 'compartmentalization' of the axoplasm of medium-sized myelinated axons, while small myelinated and unmyelinated axons underwent a more variable response ranging from electron-lucent to electron-dense changes. The affected cell body was characterized by the presence of swollen, electron-lucent mitochondria, a reduction of cytoplasmic ribosomes and a filamentous hyperplasia. Other changes often included an eccentric nucleus and satellite cell proliferation. Degenerative changes often occurred in isolated elements surrounded by normal profiles, suggesting specificity of ricin within the trigeminal ganglion. Changes within brainstem axons showed both an electron-dense and a lucent, fragmenting type of axonal alteration. Terminal changes ranged from electron-dense to lucent and also included filamentous hyperplasia and 'hyperglycogenesis'. The altered axonal knobs contained round synaptic vesicles that were presynaptic to dendritic profiles and postsynaptic to terminals containing flattened synaptic vesicles. The above brainstem alterations were identified specifically in the following areas: ventrolateral, medial and dorsomedial pars interpolaris; the ventrolateral and mid-dorsal to dorsomedial areas of the marginalis and outer substantia gelatinosa layers of pars caudalis; and in ventral pockets corresponding to lamina V of the medullary dorsal horn. Dense alterations within terminals containing flattened synaptic vesicles that are typically presynaptic to primary afferents in these areas were rare findings, but along with vacuolization of dendritic profiles suggest a trans-synaptic effect possibly due to the exocytosis of ricin. The results are discussed in relation to different reports of dental projections and with regards to patterns of transganglionic degeneration.

Animals↗
PubMed1987

Methodologic issues in the analysis of lung function data.

The forced expiratory volume in one second (FEV1) is routinely used in epidemiologic studies of lung function to assess the presence and severity of obstructive airways disease. Normative prediction equations developed using data from healthy, asymptomatic individuals may then be used both in a clinical setting and to adjust comparisons among risk subgroups for known demographic differences. Unfortunately no concensus has yet developed as to how best to model lung function data. This paper addresses this issue in a systematic manner using data derived from two cohorts followed over a period of 9-11 years. We compare a variety of cross-sectional and longitudinal models for FEV1, show how they may be expressed as members of a larger class of general linear models, and discuss goodness-of-fit procedures for comparing them. We found little objective evidence for discriminating among these models; only those fit to FEV1/ht3 performed poorly. We argue on subjective grounds for the use of models based on FEV1 as a function of age, height and their interactions.

Adult↗
PubMed1987

Effect of epidermal growth factor on polyamine-synthesizing enzymes in rat enterocytes.

A number of peptides having trophic activity on gastrointestinal mucosa and growth factors are known to induce small intestinal ornithine decarboxylase (ODC) activity. The effect of peptides on ODC and S-adenosylmethionine (SAMDC) activities (key enzymes in polyamine biosynthesis) in isolated enterocytes is unknown. Male Sprague-Dawley rats were fasted for 72 h and injected intraperitoneally with epidermal growth factor (EGF), pentagastrin, or glucagon, or intragastrically with EGF. A similar volume of water served as a control. Villus tip, midvillus, and crypt cell fractions were collected and identified. ODC and SAMDC activities were determined in these cells 4 h after peptide injection. EGF given intraperitoneally, but not intragastrically, stimulated ODC activity along the cryptvillus column. Pentagastrin and glucagon did not induce polyamine biosynthetic enzyme activity. ODC and SAMDC activities in intestinal mucosal scrapings from fasted animals also were increased 2-4 h after intraperitoneal EGF treatment. It is possible that EGF binding at the serosal surface of the crypt enterocyte and subsequent ODC induction is important in initiating the cellular proliferation that is known to occur after treatment with this peptide.

Adenosylmethionine Decarboxylase↗
PubMed1987

Role of ornithine decarboxylase in functional development of rat gastric mucosa.

The effects of inhibiting polyamine synthesis on the functional development of the gastric mucosa were studied in rats from 5 to 40 days old. They were treated from day 14 after birth with alpha-difluoromethylornithine (DFMO) at a concentration of 2% in the drinking water of mothers and pups. The rats were weaned on day 18. Basal acid and pepsin secretion, oxyntic gland mucosal pepsinogen content, and antral gastrin content followed similar developmental patterns in control animals. Levels of these parameters remained measurable but low until around the time of weaning, when dramatic log linear rises were observed. DFMO failed to delay the onset of the rises in any of these maturational indices. Ornithine decarboxylase (ODC) activity in the oxyntic gland mucosa was low but discernible in rats of every age studied. DFMO significantly reduced ODC activity at every age except 40 days, where there was no difference from control values. Our results suggest that ODC activity in the rat gastric mucosa does not change appreciably during neonatal development and that inhibiting putrescine synthesis from its precursor ornithine by DFMO treatment does not prevent or delay gastric mucosal maturation.

Age Factors↗
PubMed1987

Relationship between ornithine decarboxylase activity and gastric damage.

Hypertonic NaCl increases the activity of gastric mucosal ornithine decarboxylase (ODC). Intragastric administration of concentrated NaCl solution also induces ulcers in the glandular gastric mucosa. The relationship between ODC activity and gastric mucosal damage and the significance of ODC increases in hypertonic NaCl-treated rats are unknown. Rats were fasted 24 h before being given 1.0 ml of 3.4 M NaCl, 120 mM aspirin in 100 mM HCl or 50% ethanol intragastrically. The oxyntic gland mucosa was removed and assayed for ODC and in some experiments DNA, RNA, and protein content. DNA, RNA, and protein content were decreased by 3.4 M NaCl, and these decreases were much greater if ODC was inhibited by pretreatment with alpha-difluoromethylornithine (DFMO). Both aspirin and 3.4 M NaCl induced ODC activity 6 h later. However, DFMO increased the lesion index only in NaCl-treated rats. Although ethanol produced damage, it had no effect on ODC levels, and DFMO did not alter the severity of ethanol lesions. When different concentrations (0.4, 0.8, 1.6, 2.5, and 3.4 M) of NaCl were administered, ODC activities were increased 6 h later in rats receiving 1.6, 2.5, and 3.4 M NaCl but not lower concentrations. Gross lesions appeared in response to the 2.5 M dose and increased with increasing NaCl concentration. However, microscopic damage of the gastric mucosa occurred at all the concentrations tested. These data show that 1) ODC activation is not necessarily produced by damage, 2) in the case of NaCl, increasing damage increases ODC, and 3) ODC appears to have a role in the prevention of a recovery to damage caused by NaCl.

Animals↗