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Biomedical subjects

D L Morgan

Publications and source records attributed to D L Morgan.

At least 37 records · Page 2Linked to original sources

Passive mechanical properties of the medial gastrocnemius muscle of the cat.

1. This is a report on the history dependence of the passive mechanical properties of the medial gastrocnemius muscle of the anaesthetised cat. 2. The muscle was conditioned with an isometric contraction at the test length, or at 3 mm longer than the test length and then returned to the test length, where the level of resting tension was measured, as well as tension changes during a slow stretch. 3. The level of resting tension depended on the form of conditioning and, at the optimum length for active tension, the history-dependent component was 9 % of the total passive tension. 4. During a slow stretch, tension initially rose steeply up to a yield point, beyond which it rose more gradually. The shape of the tension rise depended on the form of conditioning. The level of tension at the yield point consisted of a stretch-dependent component, the 'short-range tension' plus the resting tension for that length. 5. The short-range tension increased with muscle length to peak close to the optimum for active tension. The slope of the tension rise during a stretch, the short-range stiffness, peaked at 2 mm beyond the optimum. 6. The short-range tension was small immediately after a conditioning contraction but grew in size as the interval was increased up to 60 s, with a time constant of 9.9 +/- 0.6 s. After a series of conditioning movements, it recovered more rapidly, with a time constant of 6.6 +/- 0.5 s. 7. The history-dependent changes in passive tension and the response to stretch are interpreted in terms of the presence, in sarcomeres of resting muscle fibres, of crossbridges between actin and myosin which have very slow formation rates, both at rest and during movements.

Actins↗

Changes in passive tension of muscle in humans and animals after eccentric exercise.

1. This is a report of experiments on ankle extensor muscles of human subjects and a parallel series on the medial gastrocnemius of the anaesthetised cat, investigating the origin of the rise in passive tension after a period of eccentric exercise. 2. Subjects exercised their triceps surae of one leg eccentrically by walking backwards on an inclined, forward-moving treadmill. Concentric exercise required walking forwards on a backwards-moving treadmill. For all subjects the other leg acted as a control. 3. Immediately after both eccentric and concentric exercise there was a significant drop in peak active torque, but only after eccentric exercise was this accompanied by a shift in optimum angle for torque generation and a rise in passive torque. In the eccentrically exercised group some swelling and soreness developed but not until 24 h post-exercise. 4. In the animal experiments the contracting muscle was stretched by 6 mm at 50 mm s(-1) over a length range symmetrical about the optimum length for tension generation. Measurements of passive tension were made before and after the eccentric contractions, using small stretches to a range of muscle lengths, or with large stretches covering the full physiological range. 5. After 150 eccentric contractions, passive tension was significantly elevated over most of the range of lengths. Measurements of work absorption during stretch-release cycles showed significant increases after the contractions. 6. It is suggested that the rise in passive tension in both human and animal muscles after eccentric contractions is the result of development of injury contractures in damaged muscle fibres.

Adult↗

On the branching of motoneurons.

Innervation ratios were estimated for motor units supplying superficial lumbrical muscles of the cat after assigning units to one of three types, FF/FI, FR, and S, and estimating their axonal conduction velocity, based on published data. Similarly, unit tensions were converted to muscle fiber number using published values for specific tension and fiber cross-sectional area. A relation was established between axonal area of cross-section and number of fibers innervated which was matched reasonably well by a model of a branching motoneuron with preterminal diameter of 4.28 microm and a daughter-to-parent ratio of 1.48 at each level of branching. It is proposed that the main features of the model are likely to apply to all motoneurons.

Animals↗

Inhalation toxicity studies of the alpha,beta-unsaturated ketones: ethyl vinyl ketone.

The National Toxicology Program is conducting a chemical class study to investigate the structure-activity relationships for the toxicity of alpha,beta-unsaturated ketones. Ethyl vinyl ketone (EVK) was selected for study because it is a representative straight-chain aliphatic alpha,beta-unsaturated ketone with extensive use and widespread exposure. Short-term inhalation studies of EVK were conducted to provide toxicity data for comparison with the related alpha,beta-unsaturated ketones 2-cyclohexene-1-one (CHX) and methyl vinyl ketone (MVK). These data will be used in designing chronic toxicity and carcinogenicity studies of these ketones. Male and female F344 rats and B6C3F1 mice were exposed to 0, 2, 4, or 8 ppm EVK 6 h/day, 5 days/wk for 13 wk. The nasal cavity was the major target organ of EVK in both rats and mice. Pathologic findings in both the olfactory and respiratory epithelium were observed. Lesions consisted primarily of olfactory epithelial necrosis, atrophy and regeneration, and/or hyperplasia and squamous metaplasia of the respiratory epithelium. Squamous metaplasia of the respiratory epithelium was present in all rats and mice exposed to 4 and 8 ppm EVK, and these lesions were more severe in rats than in mice. Few systemic effects were observed in rats and mice exposed to EVK. A transient decrease in total leukocytes due to decrements in lymphocyte and monocyte populations was present in male rats after exposure to 8 ppm for 3 and 21 days; however, this effect was not present after exposure for 13 wk. There were no chemical-related effects on micronucleus formation in mice, or on sperm motility and vaginal cytology in either species. EVK, like other alpha,beta-unsaturated ketones, is a reactive, direct-acting gaseous irritant with toxicity limited primarily to the upper respiratory tract.

Administration, Inhalation↗

Inhalation toxicity studies of the alpha,beta-unsaturated ketones: 2-cyclohexene-1-one.

2-Cyclohexene-1-one (CHX) is a cyclic alpha,beta-unsaturated ketone with broad human exposure. CHX is an environmental pollutant and is present in tobacco smoke and in soft drinks sweetened with cyclamate. Interest in the toxicity of this class of compounds is due to their structural similarity to the cytotoxin acrolein. In a pilot study, rats and mice were exposed to 0, 20, 40, or 80 ppm CHX for 6 h/day. The study was terminated after 4 days due to acute toxicity in the high-dose groups. In a subsequent 14-day study, mice and rats were exposed to 0, 2.5, 5, or 10 ppm CHX for 6 h/day. All animals survived exposure until terminal sacrifice. Body weights were not significantly different from controls after 14 days of exposure. Liver/body weights were increased in male and female mice exposed to 5 and 10 ppm, and in male and female rats exposed to 10 ppm CHX. Ninety-day toxicity studies were conducted to provide data required to design chronic toxicity and carcinogenicity studies of CHX if it is determined such studies are necessary. Groups of 10 male and female F-344 rats and B6C3F1 mice were exposed to 0, 2.5, 5, or 10 ppm CHX for 6 h/day for 13 wk. All animals survived until sacrifice. Body weights were not significantly different from controls after 13 wk of exposure. Liver weights were increased in male and female mice exposed to 5 and 10 ppm and in male and female rats exposed to 10 ppm CHX. No adverse effects on bone-marrow micronuclei, sperm motility, or vaginal cytology were observed. Microscopic lesions included hyperplasia, and squamous metaplasia in the nasal cavity in rats and mice of both sexes at all doses. Nasal-cavity erosion and suppurative inflammation also occurred in high-dose mice. Larynx and lung were not affected in either sex or species. Dose-related hepatic centrilobular cytoplasmic vacuolation was seen in male rats only. These data suggest that CHX acts as an alkylating agent primarily producing toxicity at the exposure site.

Administration, Inhalation↗

Mercury vapor and female reproductive toxicity.

Epidemiological studies finding menstrual cycle abnormalities among women occupationally exposed to Hg degrees prompted us to investigate the mechanisms of reproductive toxicity of Hg degrees in the female rat. Nose-only Hg degrees vapor inhalation exposures were conducted on regularly cycling rats 80-90 days of age in dose-response and acute time-course studies, which have previously proven useful as a model to identify ovarian toxicants. Vaginal smears were evaluated daily and serum hormone levels were correlated with cycle and with ovarian morphology at necropsy. Exposure concentration-related effects of Hg degrees were evaluated by exposing rats to 0, 1, 2, or 4 mg/m3 Hg degrees vapor 2 h/day for 11 consecutive days. Tissue Hg levels correlated with exposure concentration and duration. Exposure of rats to 4 mg/m3 (but not 1 or 2 mg/m3) Hg vapor for 11 days resulted in significant decreases in body weights relative to controls. Estrous cycles were slightly prolonged in the 2 and 4 mg/m3 dose groups, and serum estradiol and progesterone levels were significantly different in the 4 mg/m3 group compared to controls. The alterations in cycle and hormones at the 4 mg/m3 exposure concentration were attributed to body weight loss and generalized toxicity. In the time-course study, rats were exposed to 2 mg/m3 Hg degrees or air beginning in metestrus and evaluated daily for 8 days. A lengthening of the cycle was detected and morphological changes were observed in the corpora lutea (CL) after exposure for 6 days. To determine if changes in the CL and cyclicity correlated with a functional defect, rats were exposed to Hg degrees vapor and evaluated for pregnancy outcome. There were no significant effects on pregnancy rate or numbers of implantation sites when rats were exposed to 1 or 2 mg/m3 Hg degrees for 8 days prior to breeding, or when exposed for 8 days after breeding. These studies indicate that exposure to Hg degrees vapor altered estrous cyclicity, but had no significant effect on ovulation, implantation, or maintenance of first pregnancy during exposure of short duration in female rats.

Administration, Inhalation↗

Human hamstring muscles adapt to eccentric exercise by changing optimum length.

PURPOSE: It is now established that unaccustomed eccentric exercise leads to muscle fiber damage and to delayed-onset muscle soreness (DOMS) in the days after exercise. However, a second bout of eccentric exercise, a week after the first, produces much less damage and soreness. The purpose of this study was to provide evidence from muscle mechanical properties of a proposed mechanism for this training effect in human hamstring muscles. METHODS: The eccentric exercise involved 12 sets of 6 repetition "hamstring lowers," performed on specially designed equipment. Hamstring angle-torque curves were constructed for each of 10 subjects (8 male and 2 female) while they performed maximum voluntary knee extension and flexion movements on an isokinetic dynamometer. Testing sessions were performed over the week before eccentric exercise, immediately post exercise, and daily, up to 8 d post exercise. Subject soreness ratings and leg girth measurements were also made post exercise. Six subjects performed a second bout of eccentric exercise, 8 d after the first, and measurements were continued up to 10 d beyond that. RESULTS: There was a significant shift in the optimum angle for torque generation (Lo), to longer muscle lengths immediately post exercise (7.7 degrees +/- 2.1 degrees, P < 0.01), indicating an increase in series compliance within some muscle fibers. Subsequent measurements showed increases in leg girth and some muscle soreness, suggesting muscle damage. The shift in Lo persisted, even after other injury parameters had returned to normal, consistent with a training effect. Subjects also showed fewer signs of muscle damage after the second exercise bout. CONCLUSION: This is the first study to show a sustained shift in optimum angle of human muscle as a protective strategy against injury from eccentric exercise. Implications of this work for athletes, particularly those prone to hamstring strains are discussed.

Adaptation, Physiological↗

Fatigue in mammalian skeletal muscle stimulated under computer control.

Functional electrical stimulation (FES) is used to provide paralyzed human subjects with postural support and a limited range of movements. Problems encountered with FES include jerky movements from tension oscillations during stimulation and rapid muscle fatigue. In this paper, we report experiments on anesthetized cats that test a new, computer-controlled method of stimulation of the muscle nerve supply, distributed across several inputs, which reduces these problems. After 5 min of continuous, distributed stimulation of the medial gastrocnemius muscle at 6 pulses per second (pps) across 6 channels, tension fell to 55.9 +/- 3.9% (SE) of its original value. In comparison, after 5 min of synchronous stimulation of one muscle portion at 36 pps, tension fell to 11 +/- 3.7%. At higher stimulation rates, 10 pps per channel (distributed) and 60 pps (synchronous), the differences in fatigue were even greater. Similar results were obtained when an intermittent, rather than a continuous, stimulation protocol was used. These findings indicate that distributed stimulation has important advantages over other methods for applications such as FES.

Animals↗

Myeloperoxidase-positive intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBL) is an uncommon form of non-Hodgkin lymphoma that is also known as malignant angioendotheliosis, intravascular lymphomatosis, and angiotropic large-cell lymphoma. The disease is characterized by a bizarre population of neoplastic cells, which are found systemically within vascular lumina. Although originally thought to be a neoplastic process of the endothelial cells, it has since been demonstrated, by molecular techniques and immunohistochemistry, that the neoplastic cells are of lymphoid origin. The differential diagnosis of these lesions includes granulocytic sarcomas that can be distinguished from IVLBL or other lymphomas by the presence of immunohistochemical positivity for myeloperoxidase. We describe a patient with a history of a myelodysplastic syndrome who subsequently developed IVLBL, which demonstrated immunohistochemical positivity for myeloperoxidase. To our knowledge, this represents the first case of a malignant lymphoma to demonstrate such findings.

Diagnosis, Differential↗

Single-participant research design. Bringing science to managed care.

The ongoing transition to managed health care continues to have repercussions for health care providers, perhaps the most important of which is an emphasis on accountability for demonstrating the usefulness of clinical interventions. This requirement places a premium on intervention research and highlights the historically strained relationship between psychological research and professional practice. In the midst of this challenge, researchers have increasingly criticized the logic and practice of traditional null hypothesis significance testing. This article describes the history, epistemology, and advantages of single-participant research designs for behavioral scientists and professionals in clinical settings. Although its lack of correspondence with the Fisherian tradition has precluded widespread adoption, the single-participant alternative features a design power and flexibility well suited to both basic science and applied research.

Behaviorism↗

Tension changes in the cat soleus muscle following slow stretch or shortening of the contracting muscle.

1. The permanent extra tension after a stretch and the deficit of tension after a shortening in the soleus muscle of the anaesthetised cat were measured using distributed nerve stimulation across five channels. At low rates of stimulation the optimum length for a contraction was several millimetres longer than that when higher rates of stimulation were used, so that movements applied over the same length range could be on the descending limb of the full activation curve but on the ascending limb of the submaximal activation curve. 2. The extra tension after stretch and the depression after shortening were present only near the peak and on the descending limb of the length-tension curve. Effects on final tension of changing the speed and amplitude of stretches or shortenings were found to be small. 3. Statistical analysis showed that variations in the tension excess or deficit due to changing stimulus rate could be entirely attributed to the effect of stimulus rate on the length-tension relation, as when length was expressed relative to optimum for each rate, stimulus rate was no longer a significant determinant of the tension excess or deficit. 4. The extra tension after stretch and the depression after shortening disappeared if stimulation was interrupted and tension briefly fell to zero. 5. These effects were explained in terms of a non-uniform distribution of sarcomere length changes at long muscle lengths. During stretch some sarcomeres are stretched to beyond overlap while others lengthen hardly at all. During shortening some sarcomeres shorten much further than others. 6. These mechanisms have important implications for exercise physiology and sports medicine.

Analysis of Variance↗

The National Academy of Sciences offers a new framework for addressing global warming issues.

The recent landmark report by the National Academy of Sciences reviewed the science on which the Kyoto Protocol was based. NAS concluded that the policy choices and the mandatory reductions in greenhouse gases by the developed nations were based on incomplete science with significant uncertainties. In view of these uncertainties the NAS report developed a comprehensive strategic 10-year research program to address the basic issue of whether human activity that results in environmental changes is responsible for climate changes. The report provides a new framework for consideration of global warming issues. The UN International Panel on Climate Change (the UN science advisor) in its 1997 report to the Kyoto parties pointed out the confusing difference between scientific usage of the term "climate change" that distinguishes human from natural causes of change and the official usage that combines natural and human causes of changes in climate. The conclusion of the UN panel on human causes is equivocal. The 1999 report of the U.S. Global Science Research Committee also reached an equivocal conclusion on human causes and announced a 10-year research program to be developed in consultation with NAS. The precautionary measures provided in the 1992 UN Framework Convention differ from the ill-defined "precautionary principle" based on fear of uncertainty, and are consistent with the objectives of the NAS proposed research program. These developments together with the third report of the UN Intergovernmental Science Panel on developments in climate science due in 2001 merit consideration by the convention of the parties under the Kyoto Protocol.

Climate↗

Effects of body orientation, load and vibration on sensing position and movement at the human elbow joint.

Experiments were carried out to study the ability of human subjects to match the position of their forearms relative to the horizontal. The normal, arms-in-front position with the hands aligned and little forward flexion at the shoulder was called the reference position. When the arms were rotated to the side, one arm was raised, or both arms were raised, matching ability deteriorated compared with the reference position, when expressed as an increase in the standard deviation of matching errors. It was concluded that particular significance was assigned by the brain to the arms-in-front position, with the hands in their normal working space. Increases in errors were also observed when the reference arm was made weightless or its weight was increased by means of an adjustable load. This suggested that lifting the arm against gravity provided additional positional information. In a second experiment, dependence of the illusion of muscle lengthening evoked by vibration was tested after two different forms of muscle conditioning, a co-contraction of elbow muscles with the arm held flexed or with it held extended. The speed of the illusory extension of flexor muscles during their vibration increased three-fold after flexion conditioning compared with extension conditioning. Since after flexion conditioning, muscle spindles in flexor muscles are expected to be more sensitive to vibration than after extension conditioning, this observation provides additional support for the view that muscle spindles make an important contribution to kinaesthesia at the elbow joint.

Adult↗

Duplication of 1q in a child with down syndrome and myelodysplastic syndrome.

Cytogenetic analysis of bone marrow cells was performed on a 2-year-old African-American male with Down syndrome (DS) and myelodysplastic syndrome (MDS), specifically refractory anemia with excess blasts in transformation (RAEB-T). Chromosome analysis showed, in addition to the constitutional trisomy 21, a trisomy of chromosome 11 and a dup(1)(q23q31). This duplication of 1q is apparently a new chromosomal abnormality in a child with MDS. Partial trisomy of the long arm of chromosome 1 has been reported by several authors and appears to represent a nonrandom chromosomal anomaly in patients with MDS/acute myelogenous leukemia and DS.

Anemia, Refractory, with Excess of Blasts↗

Occurrence of monomethylarsonous acid in urine of humans exposed to inorganic arsenic.

Monomethylarsonous acid (MMA(III)) has been detected for the first time in the urine of some humans exposed to inorganic arsenic in their drinking water. Our experiments have dealt with subjects in Romania who have been exposed to 2.8, 29, 84, or 161 microg of As/L in their drinking water. In the latter two groups, MMA(III) was 11 and 7% of the urinary arsenic while the monomethylarsonic acid (MMA(V)) was 14 and 13%, respectively. Of our 58 subjects, 17% had MMA(III) in their urine. MMA(III) was not found in urine of any members of the group with the lowest level of As exposure. If the lowest-level As exposure group is excluded, 23% of our subjects had MMA(III) in their urine. Our results indicate that (a) future studies concerning urinary arsenic profiles of arsenic-exposed humans must determine MMA(III) concentrations, (b) previous studies of urinary profiles dealing with humans exposed to arsenic need to be re-examined and re-evaluated, and (c) since MMA(III) is more toxic than inorganic arsenite, a re-examination is needed of the two hypotheses which hold that methylation is a detoxication process for inorganic arsenite and that inorganic arsenite is the major cause of the toxicity and carcinogenicity of inorganic arsenic.

Adolescent↗

Upper respiratory tract toxicity of inhaled methylvinyl ketone in F344 rats and B6C3F1 mice.

The National Toxicology Program is conducting a chemical class study to investigate the structure-activity relationships for the toxicity of alpha,beta-unsaturated ketones. Methylvinyl ketone (MVK) was selected for study because it is a representative straight-chain aliphatic alpha,beta-unsaturated ketone and because of its extensive use and widespread exposure. Short-term inhalation studies of MVK were conducted to provide toxicity data for comparison with other alpha,beta-unsaturated ketones and for use in designing chronic toxicity and carcinogenicity studies. In 2-week studies, rats and mice were exposed to 0, 0.25, 0.5, 1, 2, 4, or 8 ppm MVK 6 h/day, 5 days/week for 12 exposures. Morbidity and early deaths occurred in all male and female rats after 1 exposure and in 2 male mice after 10 exposures to 8 ppm. Rats exhibited nasal cavity toxicity and lung necrosis at 4 ppm. No toxicity was observed in animals exposed to less than 2 ppm. Based on these results a 13-week study was conducted at 0, 0.5, 1, and 2 ppm MVK. As observed in the 2-week study, the nasal cavity was the main target organ and rats were more sensitive than mice. Respiratory and olfactory epithelial necrosis were prominent by day 21 in the rat. At study termination these lesions were still evident but not as severe as noted earlier. Additionally, changes such as olfactory epithelial regeneration and metaplasia (respiratory) as well as respiratory epithelial hyperplasia and metaplasia (squamous) were clearly evident. Nasal lesions in mice were limited to a subtle squamous metaplasia of transitional and/or respiratory epithelium covering predominantly the tips of naso- and maxilloturbinates in Levels I and II. A transient, leukopenia was observed in rats exposed to 2 ppm, however, this effect was not present after 13 weeks of exposure. In mice, leukocyte counts were significantly decreased at all exposure concentrations after 13 weeks of exposure. Absolute testicular and epididymal weights and sperm counts were decreased at the high dose only. MVK can be characterized as a reactive, direct-acting gaseous irritant. MVK exposure causes the same nasal cavity lesions as the cyclic alpha,beta-unsaturated ketone, 2-cyclohexen-1-one, although at lower exposure concentrations.

Administration, Inhalation↗

Airway fibrosis in rats induced by vanadium pentoxide.

Vanadium pentoxide (V(2)O(5)) is a cause of occupational asthma and bronchitis. We previously reported that intratracheal instillation of rats with V(2)O(5) causes fibrosis of the lung parenchyma (J. C. Bonner, P. M. Lindroos, A. B. Rice, C. R. Moomaw, and D. L. Morgan. Am. J. Physiol. Lung Cell. Mol. Physiol. 274: L72-L80, 1998). In this report, we show that intratracheal instillation of V(2)O(5) induces airway remodeling similar to that observed in individuals with asthma. These changes include airway smooth muscle cell thickening, mucous cell metaplasia, and airway fibrosis. The transient appearance of peribronchiolar myofibroblasts, which were desmin and vimentin positive, coincided with a twofold increase in the thickness of the airway smooth muscle layer at day 6 after instillation and preceded the development of airway fibrosis by day 15. The number of nuclear profiles within the smooth muscle layer also increased twofold after V(2)O(5) instillation, suggesting that hyperplasia accounted for thickening of the smooth muscle layer. The majority of cells incorporating bromodeoxyuridine at day 3 were located in the connective tissue surrounding the airway smooth muscle wall that was positive for vimentin and desmin. These data suggest that myofibroblasts are the principal proliferating cell type that contributes to the progression of airway fibrosis after V(2)O(5) injury.

Animals↗