Biomedical subjects
Publications and source records attributed to R L Jones.
Monoclonal gammopathy associated with plasmacytic gastroenterocolitis was diagnosed in a dog. Treatment consisted of immunosuppressive drugs and dietary manipulation. The gammopathy resolved. Fifteen months after initial diagnosis, the dog had a relapse of intestinal disease and recurrence of the gammopathy. After inducing a second remission, the gammopathy again resolved.
The effects of gibberellic acid (GA3) and abscisic acid (ABA) on the temporal and spatial dynamics of cytosolic calcium concentration ([Ca2+]i) in aleurone protoplasts of barley (Hordeum vulgare L. cv. Himalaya) were measured by using fluorescence ratio analysis and confocal microscopy. After 4-6 h of treatment, GA3 induced a sustained increase in [Ca2+]i from 50 to 150 nM in aleurone protoplasts. The increase in [Ca2+]i preceded the GA3-induced increase in alpha-amylase synthesis and secretion by 4 h. The elevation of [Ca2+]i was highest in the peripheral cytoplasm and may play a role in coordinating the secretory events there. Reducing Ca2+ levels in the incubation medium to below 500 microM inhibited the increase in [Ca2+]i and the GA3-induced stimulation of alpha-amylase synthesis and secretion. These data suggest that GA3 may increase [Ca2+]i by increasing the influx of Ca2+ at the plasma membrane. ABA reversed the effect of GA3 on [Ca2+]i within 3 h, 2 h before its effect on alpha-amylase production could be detected. Thus changes in [Ca2+]i may play a role in mediating the effects of GA3 and ABA on the synthesis and secretion of alpha-amylase in the aleurone cell.
Overall lung volumes, regional residual volume to total lung capacity ratio (RVr/TLCr), regional ventilation (V/V) and perfusion (Q/V) were measured at 670 m in six Quechua Indians on days 2 and 37 after leaving their high-altitude homes (3500-4500 m). On day 2 the lung volumes averaged between 124 and 137% of those predicted for low-altitude residents (LAR) and there were no significant changes on day 37. Although overall RV/TLC was not different from the predicted value for LAR, RVr/TLCr on day 2 was higher at the top and lower at the bottom of the lungs compared to LAR. Regional Q/V and V/V were not different from LAR on day 2, or on day 37. However, the ratio of Q/V at the bottom to Q/V at the top was 2.36 on day 2 and 2.84 on day 37 (P less than 0.05). On day 2 hemoglobin- and volume-corrected diffusing capacity was 145% of the value predicted for LAR and this fell to 135% predicted on day 37 (P less than 0.05). Natives of high altitude reportedly have more alveoli that LAR and this could explain the greater vital capacity toward the bottom of the lung if the alveolar proliferation is concentrated there. This might also lower pulmonary vascular resistance at the bottom which would explain the normal Q/V distribution, even though pulmonary artery pressure may be increased.
Induction of hyperploidy in germ cells of male Chinese hamsters treated with vincristine at dose levels of 0.25, 0.50 or 0.75 mg/kg of body weight was investigated. Animals were killed at 6, 24, 48, 72 and 96 h after administration of the chemical by a single intraperitoneal injection. The testes were removed and processed for spermatogonial, meiotic I, and meiotic II metaphases. Significantly increased frequencies of hyperploidy were obtained in meiotic II cells harvested 6, 24 and 48 h but not 72 and 96 h after treatment, indicating the importance of multiple sampling times. Analysis of spermatogonial cells shows that the frequencies of hyperploidy in the treated samples were comparable to those of controls. Limited sampling times used in the present study as well as small sample size or possible loss of hyperploid cells may be responsible for the negative findings for spermatogonial cells. Examination of meiotic I cells from 53 animals reveals the presence of one animal with an elevated level of hyperploidy unrelated to the vincristine treatment.
1. Prostaglandin E2 (PGE2) relaxes circular smooth muscle of the rabbit isolated jugular vein at very low concentrations (mean pIC50 against histamine-induced contraction = 9.34). This effect is not blocked by the EP1-receptor antagonist, AH 6809 (2 microM). 2. From a group of prostaglandin E analogues examined, 16,16-dimethyl PGE2, misoprostol, 11-deoxy PGE2-1-alcohol and 11-deoxy PGE1 were highly potent relaxant agents, whereas 17-phenyl-omega-trinor PGE2, MB 28767 and butaprost had low potency and sulprostone and oxoprostol were virtually inactive. 3. Comparison of the jugular vein data with published data for inhibitory agonist potencies on the cat trachea (EP2 preparation) and the field-stimulated guinea-pig vas deferens (EP3) indicates that the EP-receptor in the rabbit jugular vein is closest to the EP2 subtype. However, the correlation is not entirely convincing. For example, butaprost, 16,16-dimethyl PGE2 and 11-deoxy PGE1 are of similar potency on the cat trachea, whereas butaprost is about 300 times less potent than the other two analogues on the jugular vein. The existence of more than one EP2-receptor appears possible. 4. It was felt that the activity of butaprost required further investigation in view of the claim that it is a specific EP2-receptor agonist. We have shown that butaprost has very low inhibitory activity on the guinea-pig vas deferens, a very sensitive EP3-receptor containing preparation. However, on the chick ileum, the original EP3 preparation, butaprost showed potent contractile activity (pEC25 approximately 8.0).In addition, its maximum response was lower than that of PGE2; lower maxima were also found for sulprostone, MB 28767 and oxoprostol, but not for ICI 80205, 16,16-dimethyl PGE2 and 17-phenyl-omega-trinor PGE2. The maximal response to a combination of either sulprostone and butaprost or sulprostone and PGE2 was similar to that achieved by PGE2 alone. Analysis of the interaction between sulprostone and PGE2 appears to exclude a partial agonist action for sulprostone. Furthermore neither sulprostone nor butaprost appear to have inhibitory activity on the ileum. AH 6809 at 2 pM produced only a small shift of the PGE2 log concentration-response curve.5. It is likely that contraction of the longitudinal smooth muscle of the chick ileum is mediated by (at least) two EP-receptor subtypes; activation of only one receptor system does not induce the maximum response (i.e. the acetylcholine maximum) of the preparation. One receptor could be an EP3 subtype, at which sulprostone exerts a selective agonist action. The other receptor is unlikely to be an EP, subtype, because of the high agonist potency of butaprost, the low agonist potency of iloprost, and the low antagonist potency of AH 6809. An alternative hypothesis is that the chick ileum contains a novel EP-receptor subtype in addition to an EP3-receptor.
1. A study of the effects of prostaglandin E2 (PGE2) and eleven synthetic analogues on the guinea-pig isolated ileum preparation has revealed three distinct contractile actions, each associated with a different prostaglandin E (EP-) receptor subtype. In addition, PGI2 (prostacyclin) and its stable analogues can activate prostaglandin I (IP-) receptors to elicit both contraction and relaxation of the ileum. 2. Two of the PGE actions involve direct stimulation of the smooth muscle, being unaffected by 1 microM morphine treatment. One action is blocked by AH 6809 at micromolar concentrations and ICI 80205 and 16,16-dimethyl PGE2 are particularly potent agonists. Activation of EP1-receptors appears to be involved. The second action is unaffected by AH 6809; sulprostone and MB 28767 are potent agonists. Comparison with agonist potency rankings on the guinea-pig vas deferens indicates that EP3-receptors may be involved. 3. The third PGE effect and the stimulant PGI effect are blocked by morphine, indicating enteric neurones and/or sensory nerve terminals as sites of action. EP2-receptors may be involved in the PGE action, in view of the marked effect of morphine on the contractile actions of misoprostol, 11-deoxy PGE2-1-alcohol, 11-deoxy PGE1 and butaprost, all of which show some selectivity for EP2-receptors. The PGI action is most easily studied with cicaprost (EC25 = 1.3 nM), since iloprost, carbacyclin and to a lesser extent PGI2 also have agonist activity at EP1-receptors. 4. The contractile action of 17-phenyl-omega-trinor PGE2 on the ileum is unaffected by morphine. Since this analogue shows only weak agonist activity on the rabbit jugular vein (EP2 preparation) and guinea-pig vas deferens (EP3), it may be a more useful standard agonist than PGE2 in EPl1-receptor studies.5. In the presence of morphine and AH 6809, cicaprost inhibits histamine-induced contractions (IC25 = 22 nM). PGI2 and iloprost show mixed inhibitory/potentiating actions, whereas carbacyclin only potentiates histamine contractions. This IP-receptor-mediated inhibition may account for the bell-shaped log concentration-response curve of cicaprost (no inhibitors present) and the very marked block of iloprostinduced contractions by AH 6809.6. We have found no evidence for either IP-receptors mediating direct contraction or EP-receptors mediating inhibition of the ileum longitudinal smooth muscle, as has been suggested in the literature.7. In view of the complexity of prostanoid action on the guinea-pig ileum we feel that the preparation must be used with caution to ascertain the EPl agonist or antagonist potencies of novel compounds.
The message of the Streptomyces fradiae aph gene lacks a leader sequence and therefore is translated in the absence of a conventional Shine-Dalgarno interaction between mRNA and 30S ribosomal subunits. Insertion mutations generating short leaders of 2 or 4 nucleotides on the 5' end of the aph transcript reduced translational efficiency. A 4-base leader (5'-AUGC-3') placing a potential out-of-frame start codon immediately upstream of the aph coding sequence prevented detectable translation in the aph reading frame. The upstream AUG in this mutant was able to drive the expression of a reporter gene in a translational fusion vector, implying that this start codon was utilized in favor of the downstream AUG. Additional leaders (5'-AUAUGC-3' or 5'-CAUAUGC-3') placing 2 or 3 nucleotides 5' to the upstream AUG relieved this apparent discrimination, permitting translation of the APH protein from the downstream AUG. These results suggest that the position of a start codon with respect to the 5' terminus of aph mRNA is a determinant of translational efficiency and start site selection.
We evaluated the efficacy of 3 treatments for chronic obstructive pulmonary disease in horses: prednisone (400 mg/horse, PO, daily; n = 7), methyl sulfonmethane (10 g/horse, PO, q 12 h; n = 6), and clenbuterol hydrochloride (0.4 mg/horse, PO, q 12 h; n = 7). A fourth group acted as controls (n = 6) and was not treated. The treatment period lasted 10 days. Each horse was a member of 2 different groups for 10 days, separated by an 18-day interval of no treatment. All horses were housed together in an outdoor pen without bedding. Horses were fed alfalfa/grass hay mix ad libitum from a large feeder. The same batch of hay was fed throughout the study. Multiple physical and laboratory variables were monitored prior to, during, and at the end of each 10-day trial period. Changes in lung sounds, respiratory effort, degree of anal movement, nasal discharge, temperature, respiratory rate, or heart rate were not significant. Changes in arterial blood gas tensions, tracheal wash or bronchoalveolar lavage cytologic findings, or phagocyte function were not significant. All horses were tachypneic and most were tachycardic. The median value for PaO2 was below normal for all horses. All tracheal wash and most bronchoalveolar lavage cytologic findings represented a suppurative response. Negative linear correlation was observed between PaO2 and degree of respiratory effort in these horses (eg, as PaO2 decreased, the degree of respiratory effort increased).
The abomasa of 1,949 slaughtered feedlot cattle, 45 necropsied feedlot cattle that died 2 to 45 days after arrival, and 45 necropsied pastured cattle were opened and examined. Of these organs, 484, 1, and none, respectively, contained erosions. The slaughtered cattle were fattened at 3 locations: 1,305 with 430 eroded abomasa were fed a ration of corn in northeastern Colorado; 144 cattle with 4 affected abomasa fed a ration of milo in south-central Arizona; and 500 cattle with 50 affected abomasa fed a ration of milo and corn in northwestern Texas. The red-brown lesions developed late during the second semester of fattening and were located mostly on fundic folds. Those on fold edges were linear and were 2 to 15 cm long, whereas those on fold sides were punctate and were 2 to 15 mm in diameter. Normal fold edges contained fewer goblet cells and less surface mucus than did fold sides. Eroded folds had disruption of surface epithelium, damage to endothelial cells, and dilated, thrombosed, congested, and ruptured capillaries. Mean pH values of 16 normal and 17 eroded abomasa were 4.7 and 3.9, respectively. Necrosis of all tissue toward the mucosal surface of erosions was extensive. The cause of gastric erosion in cattle is not known.
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Secondary cataract growth commonly occurs after extracapsular cataract extraction. The proliferation of this regrowth occurs at rates related to many factors. In this study, the authors analyzed the amount of lens regeneration after endocapsular lens extraction that leaves the anterior and posterior capsules relatively intact. The analysis was performed in New Zealand albino rabbits with the aid of image analysis measurements in young and adult animals. The effect of low vacuum suction of the anterior capsule on the growth was determined. Lens regeneration was used as a measure of the growth potential of the leftover epithelial cells in the capsule bag. The results showed that lens regeneration was significantly faster in younger rabbits. However, low vacuum suction had no effect on the growth rate. Potential therapeutic agents for preventing secondary cataracts may be better analyzed with image analysis processing of lens regeneration, a precise and rapid measurement technique.
There are 300,000 to 1,215,000 high-school football injuries each year in the United States. These injuries have an important effect on player participation and health care costs. This study investigates what portion of injuries occur during the third quarter of a game, and if completing a warm-up and stretching routine after halftime reduces the incidence of third-quarter injuries. Intervention-group teams participated in a prescribed three-minute warm-up and stretching routine following the halftime break. The control group received no warm-up and stretching intervention. Fifty-five games with 108 total injuries were examined. Overall, ligament sprains and muscle strains were the most common type of injury (38%). In the nonintervention group, injuries occurred most often in the third quarter. Intervention teams sustained significantly fewer third-quarter sprains and strains per game (p less than 0.05), although no significant difference in total third-quarter injuries was noted. These findings suggest an association between post-halftime warm-up and stretching and reduced third-quarter sprain and strain injuries. We suggest a larger-scale, randomized confirmatory study.
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Two alpha-D-glucans, produced from amylopectin by an oral isolate Streptococcus sanguis 1 MC 204, were shown to contain both (1----4) and (1----6) linkages. The first alpha-D-glucan (amyloglucan) was adherent and highly insoluble, and methylation analysis, i.r. spectroscopy, and enzymic analyses showed it to be similar to amylopectin but less branched with longer interior and exterior chains. The second polymer was a non-adherent soluble alpha-D-glucan that was similar to amyloglucan but with long exterior chains. These alpha-D-glucans were not synthesised de novo, but were the products of the modification of amylopectin.
Full-unit transfusions of RBC enzymatically converted from group B to group O by treatment with alpha-galactosidase (ECO RBC) to group O and A normal healthy individuals exhibit excellent in vivo survival times (24-hour survival 95.1% +/- 2.3%, T50 36.9 +/- 4.6 days). These results confirm our earlier findings describing ECO RBC in vitro viability and normal in vivo survival time after small-volume infusions. No significant increase in pretransfusion anti-B titer or score is observed in either group O or A subjects provided that sufficient enzyme is used to treat the cells: Cells transfused to group O recipients require higher levels of enzyme (185 to 200 U/mL RBC) than those infused to group A (90 U/mL RBC). Two separate single-unit transfusions of ECO RBC to one group O recipient (4.5 months apart) also survived normally (24-hour survival 96% and 92%, T50 40 and 36 days) and did not increase preexisting anti-B levels in this subject. ECO RBC were not agglutinated or lysed by recipient sera before or after transfusion. Similarly, no antibody development to the alpha-galactosidase used in cell treatment (and washed from the product before transfusion) could be detected in any subject. The sustained increase in hemoglobin levels after transfusion of ECO RBC suggests that this product will be useful in treatment of acute and chronic anemia.
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Bacterial translocation is proposed as an explanation for sepsis associated with hemorrhagic shock. This study attempted to document these events in a large animal model. Male swine were randomly assigned to control (n = 10) or experimental (n = 10) groups. Animals were anaesthetized, and the bladder, portal vein, and a mesenteric lymphatic vessel cannulated. Experimental animals were bled 40% of blood volume. Over the next six hours maintenance fluids were given, and cultures of portal blood and mesenteric lymph taken. Before the swine were killed, cultures were taken from portal and systemic blood, mesenteric lymph, and lymph nodes, and a portion of terminal ileum was resected for histologic study. Experimental animals experienced significant shock as demonstrated by changes in hemodynamic and biochemical variables. Cultures and histologic examination of the terminal ileum showed no significant difference between control and experimental animals. In an unresuscitated swine model, significant bacterial translocation was not demonstrated within six hours of hemorrhagic shock.