Successful coronary angioplasty in two patients with cardiogenic shock using the Nimbus Hemopump support device.
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Aged↗
Biomedical subjects
A M Kelly
Publications and source records attributed to A M Kelly.
Stability properties of two supports for immobilization of enzymes.
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Ceramics↗
ski can cause selective growth of skeletal muscle in transgenic mice.
We have created several lines of mice that contain a truncated chicken c-ski cDNA linked to an MSV LTR promoter. Adult mice from three independent lines show large increases in skeletal muscle. All three lines of mice express high levels of c-ski mRNA and protein in skeletal muscle. All other tissues examined show little or no expression of the c-ski transgene. The muscles of one of the three lines were examined in more detail. Type II fast fibers undergo selective hypertrophy in affected muscles of this line.
Animals↗
Isoform-specific cDNAs for human embryonic, neonatal, and slow skeletal myosin heavy chains.
A series of cDNA fragments encoding immunodetectable portions of the human slow/beta, neonatal, and embryonic isoforms of myosin heavy chain (MHC) were isolated from a human fetal muscle cDNA expression library. A 6 kb fragment isolated on a secondary screen represents the first cloned cDNA encoding a full-length vertebrate MHC (the human embryonic isoform). In the 3'-untranslated regions, 70-80% nucleotide sequence homology exists among orthologous human and rat cDNAs, whereas the homology is less than 65% among the paralogous cDNAs. Furthermore, approximately the same level of untranslated sequence conservation is observed at the 5'-terminus of the embryonic transcript. These results suggest that for both the 3'- and the 5'-untranslated domains, the rate of evolutionary sequence divergence is limited by functional constraints.
Amino Acid Sequence↗
Histamine stimulates proliferation of airway smooth muscle and induces c-fos expression.
Although chronic severe asthma is characterized by increased smooth muscle mass in the airways, the physiological stimuli that promote airway smooth muscle (ASM) proliferation (hyperplasia) or increase ASM protein expression (hypertrophy) are unknown. We examined the effects of histamine, an autocoid associated with airway hyperresponsiveness, on protein synthesis, myosin heavy chain expression, and cell proliferation in cultured canine ASM cells. In confluent ASM cells, histamine significantly increased incorporation of [35S]-methionine in protein. Maintenance of the proportion of smooth muscle-specific myosin heavy chain to total myosin heavy chain suggested a nonspecific increase in contractile protein expression. DNA synthesis, as measured by [3H]thymidine incorporation, was significantly increased by histamine in a concentration-dependent manner. Cell proliferation paralleled [3H]thymidine incorporation; histamine significantly increased cell numbers at 24 and 48 h of stimulation. Because growth of mesenchymal-derived cells is associated with transcription of c-fos mRNA, we examined whether histamine altered expression of this proto-oncogene. Histamine-treated cells showed marked increases in expressions of steady-state c-fos mRNA, with a time course of mRNA induction similar to cells exposed to platelet-derived growth factor or serum, known smooth muscle and fibroblast cell mitogens. Therefore, histamine is an ASM mitogen with an action similar to other mesenchymal cell growth factors and may play a role in the hyperplasia of ASM in asthma.
Animals↗
Human embryonic myosin heavy chain cDNA. Interspecies sequence conservation of the myosin rod, chromosomal locus and isoform specific transcription of the gene.
A 3.6 kilobase cDNA clone coding for the human embryonic myosin heavy chain has been isolated and characterized from an expression library prepared from human fetal skeletal muscle. The derived amino acid sequence for the entire rod part of myosin shows 97% sequence homology between human and rat and a striking interspecies sequence conservation among the charged amino acid residues. The single copy gene is localized to human chromosome 17 and its expression in fetal skeletal muscle is developmentally regulated. The sequence information permits the design of isoform-specific probes for studies on the structure of the gene and its role in normal and defective human myogenesis.
Amino Acid Sequence↗
Nucleotide sequence of full length human embryonic myosin heavy chain cDNA.
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Base Sequence↗
Fibre types in Limulus telson muscles: morphology and histochemistry.
Using a variety of techniques, we have demonstrated the presence of at least two fibre types in Limulus median telson levator muscle. By light and electron microscopy, large (2,156 microns 2 mean cross-sectional area) fibres have A-bands of 4.1 microns, one-half I bands of 2.15 microns and Z lines less than or equal to 0.5 microns in width. Few mitochondria are found in these fibres, which comprise 54% of those present in a given microscope field and which occupy 82% of the total cross-sectional area. Small fibres (484 microns 2 mean cross-sectional area) have A bands of 6.3 microns, one-half I bands of 3.1 microns and Z lines between 0.5 and 1.0 microns in width and are rich in mitochondria. Although small fibres comprise nearly one-half (46%) of the fibres in a field, they occupy only 18% of the total cross-sectional area. Histochemical staining for alkaline-stable myofibrillar ATPase activity and mitochondrial reduced beta-nicotinamide adenine nucleotide (beta-NADH) tetrazolium reductase activity confirms the presence of two fibre types. The large fibres react positively for the myofibrillar ATPase activity and negatively for the mitochondrial enzyme activity. The reverse is seen with the small fibres. Some fibres of intermediate size, having intermediate staining characteristics, were also observed. Native gel electrophoresis of both myofibrillar and purified myosin preparations supports the observed differences in myofibrillar ATPase activity in that two myosin isozymes are resolved on pyrophosphate gels. Although the thick filaments isolated from unstimulated small fibres are longer (greater than 6.0 microns) than those isolated from unstimulated large fibres (4.26 microns), all have a similar appearance with respect to the arrangement of myosin heads on their surfaces, and similar diameters. The implications of the observed heterogeneity of fibre types is discussed with reference to previously reported phenomena in Limulus telson muscle, including changes in length of thick filaments on fibre stimulation and the shape of the length-tension curve obtained from fibre bundles.
Animals↗
Metabolic specialization in fast and slow muscle fibers of the developing rat.
Individual fibers of prospective fast (extensor digitorum longus; EDL) and slow (soleus) muscles of rats have been analyzed to determine the profiles of key energy-generating enzymes at successive stages of postnatal development. Mean activities of lactate dehydrogenase (LDH) and adenylokinase (AK), 2 enzymes associated with contractile function, are significantly different in the 2 fiber populations at birth; furthermore, wide variations in enzyme activities exist among the individual fibers. There is a progressive refinement of enzyme levels in the soleus into a more uniform fiber population, while the fibers in the EDL progressively diverge into 2 distinct phenotypes. Changes in EDL and soleus are punctuated by periods of rapid change, with the period between 10 and 21 d being most eventful. Generally, the maturation profiles of LDH and AK coincide with the transition from neonatal to adult fast myosins and closely reflect the timing of energy demands imposed by contractile activity patterns. In contrast, activities of the oxidative enzymes malate dehydrogenase and beta-hydroxyacyl CoA dehydrogenase are similar in both muscles at birth and steadily increase during the first 3 weeks, suggesting a progressive adaptation to the aerobic extrauterine environment. After 30 d, there are differential changes in the oxidative profiles of enzymes for fatty acid and glucose metabolism. The profiles follow dietary changes associated with weaning, which suggests a phenotypic dependence of neonatal muscle on the particular available energy substrate. All enzymes are low in all fibers of EDL and soleus at birth, indicating their modest metabolic capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxyacyl CoA Dehydrogenases↗
Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women.
The effect of long-term L-thyroxine (L-T4) therapy on axial skeleton bone density was studied in 31 premenopausal women; the bone densities of these women were compared with the bone densities of 31 age- and weight-matched women without thyroid or bone abnormalities. The women receiving L-T4 therapy had been receiving the medication for a minimum of five years. There was no difference in calcium intake or excretion between the L-T4-treated women and the controls. Women receiving L-T4 had increased serum thyroxine concentrations (134 +/- 5 vs 95 +/- 3 nmol/L [10.4 +/- 0.4 vs 7.4 +/- 0.2 micrograms/dL]), an increased free thyroxine index (9.4 +/- 0.4 vs 6.8 +/- 0.2), and decreased serum thyroid-stimulating hormone concentrations (0.9 +/- 0.2 mU/L vs 2.1 +/- 0.3 mU/L [0.9 +/- 0.2 vs 2.1 +/- 0.3 microU/mL]). Serum triiodothyronine concentrations were normal and were similar in both groups. Women treated with L-T4 had a 12.8% lower bone density at the femoral neck and a 10.1% lower bone density at the femoral trochanter compared with matched controls. In contrast, lumbar spine bone density was similar in the two groups. The data suggest that long-term L-T4 therapy, which is often given at supraphysiologic dosages, may predispose patients to decreased bone density in the hip and may increase the risk of age-related bone loss. It is advisable, therefore, to employ a dosage of L-T4 that is carefully monitored to avoid the long-term use of dosages that are excessive for the thyroid condition being treated.
Adult↗
Hormonal control of myosin heavy chain genes during development of skeletal muscles.
A pattern of myosin heavy chain (MHC) switching is a hallmark of developing muscles. Factors responsible for these changes in gene expression include endogenous signals, motoneurons and hormones, especially thyroid hormones. After perturbing the innervation and/or thyroid hormone levels we have examined the neonatal-IIb MHC transition during rat development. First, denervation does not qualitatively affect the transition at either the transcriptional or translational level. Second, hypothyroidism prevents the appearance of IIb MHC and its mRNA in the innervated limb; in the denervated hypothyroid limb IIb MHC is synthesized at moderately high levels. Third, hyperthyroidism causes a precocious increase in IIb MHC in both innervated and denervated muscles. These results suggest that the transition from neonatal to adult IIb myosin synthesis is endogenously programmed during development, but is closely orchestrated by the changing neuronal and hormonal status of the animal. Thyroid hormone may exert its influence by effects both on the muscle fibre and on the developing motoneuron. In the guinea-pig the temporalis muscle is sexually dimorphic: it contains a fast-red MHC in the female but a fast-white MHC in the male. This dimorphism has been shown to be mediated by testosterone, since the castrated male synthesizes the fast-red MHC while the testosterone-supplemented female contains the fast-white MHC. During development male and female muscles initially synthesize the fast-red isoform. The male switches to the fast-white form at puberty.
Animals↗
Ultrasound attenuation of the os calcis in women with osteoporosis and hip fractures.
Bone ultrasound attenuation of the calcaneus, and vertebral and femoral bone density measured by dual photon absorption were determined in 22 women with osteoporosis, 10 women with hip fractures, and 29 normal, age-matched controls to determine the utility of the ultrasound technique as an indicator of axial osteopenia. Vertebral and femoral neck density and bone ultrasound attenuation were significantly decreased (P less than 0.01) in the women with osteoporosis and those with hip fractures. The sensitivity and specificity of bone ultrasound attenuation was 80% at a value of 50 dB/MHz. At 90% specificity the sensitivity of bone ultrasound attenuation was 65%. The results of this pilot study suggest that ultrasound attenuation, a safe, simple, and radiation-free procedure, may be utilized as an indicator of decreased axial bone mass.
Aged↗
Dermatologic lesions in a transplant population.
Many authors have reported an increase in the incidence of skin neoplasia in renal transplant patients. Two hundred and twenty-three patients, who received a renal transplants between 1965 and 1984, were examined for the presence of skin lesions. There was a high incidence of simple warts (24%) and hyperkeratoses (21%). Frank malignancy had developed in 9 patients; this is more than 4 times the expected incidence for the population of Northern Ireland.
Adolescent↗
Biochemical studies of canine muscle phosphofructokinase deficiency.
Skeletal muscle from four dogs with erythrocyte phosphofructokinase (PFK; EC 2.7.1.11) deficiency were studied in vitro. Muscle PFK activities were severely decreased to 1% of the normal mean. The residual activities had a high Km for fructose-6-phosphate (F6P). Anaerobic lactate production of PFK-deficient muscle was minimal with the addition of glycogen and hexose-monophosphates, but was normal with fructose-1,6-diphosphate (FDP). Muscle glycogen concentration was twice normal, indicating a glycogen storage disorder. Histochemical studies for muscle PFK activity showed no enzymatic staining with F6P as substrate. In two muscle biopsies from asymptomatic related dogs, intermediate PFK activities were found. These data characterize canine muscle PFK deficiency in vitro.
Animals↗
Lysophosphatidylinositol: a potential mediator of 1,25-dihydroxyvitamin D-induced increments in hepatocyte cytosolic calcium.
Recent studies in our laboratory demonstrate that 1,25-dihydroxyvitamin D [1,25-(OH)2D] increases hepatocyte cytosolic calcium in the absence of extracellular calcium and activates phospholipase-A-induced deacylation of phosphatidylinositol within 5 min. To determine whether inhibition of phospholipase-A affects D-induced increments in cytosolic calcium and which metabolite of phosphatidylinositol mediates these increments, cytosolic calcium is measured in cultured hepatocytes, loaded with Fura 2AM. Cellular fluorescence is determined at excitation wavelengths of 340 and 380 nm, and cytosolic calcium is calculated. 1,25-(OH)2D treatment for 5 min increases cytosolic calcium levels in the cultured hepatocyte. Inhibition of phospholipase-A with bromophenacylbromide blocks the vitamin D effect on cytosolic calcium, indicating that phospholipase-A activation precedes increments in cytosolic calcium. Neither arachidonic acid nor sodium arachidonate affects cytosolic calcium. In contrast, LPI increases hepatocyte cytosolic calcium in the presence and absence of extracellular calcium. The effect is not blocked by bromophenacylbromide. Neither cell viability nor supernatant fluorescence is altered by LPI, indicating that LPI is increasing fluorescence within the cell. 1,25-(OH)2D treatment for 5 min increases cytosolic pH in cultured hepatocytes. Inhibition of cell alkalinization with amiloride blocks the vitamin D effect on both cytosolic pH and cytosolic calcium, but not the effect of LPI on calcium. NH4Cl increases hepatocyte pH but not cytosolic calcium. The results indicate that phospholipase-A activation is necessary for 1,25-(OH)2D-induced increments in hepatocyte cytosolic calcium and that LPI, a deacylation product of phosphatidylinositol, mediates these increments. Furthermore, inhibition of Na+/H+ exchange, while not blocking the ability of the cell to increase cytosolic calcium in response to LPI, prevents the 1,25-(OH)2D-induced increments in both pH and calcium. The data suggest that the rapid effects of 1,25-(OH)2D on hepatocyte calcium are preceded by cell alkalinization and phospholipase-A activation, and these effects appear to be linked to the Na+/H+ antiport system and not nonspecific cell alkalinization.
Acetophenones↗
Biological effect of epidermal growth factor on the in vitro growth of human tumors.
The effect of epidermal growth factor (EGF) on the in vitro growth of 186 malignant human tumor specimens (45 melanomas, 32 sarcomas, and 56 lung, 16 gynecological, 14 breast, 12 genitourinary, and 11 gastrointestinal carcinomas) was evaluated in the cellular adhesive matrix human tumor culture system supplemented with transferrin, insulin, hydrocortisone, and estradiol. EGF increased tumor growth by at least 50% in 81% of the 186 tumors and by over 100% in 54%. The enhanced growth induced by EGF was related to an accelerated cellular division independent of tumor type and not to an increase in the actual number of clonogenic units. The drug concentrations of cell cycle-independent Adriamycin and cisplatin needed to achieve a 90% tumor cell kill were not altered by the responsiveness of the tumor to EGF.
Antineoplastic Agents↗
Slow myosin in developing rat skeletal muscle.
Through S1 nuclease mapping using a specific cDNA probe, we demonstrate that the slow myosin heavy-chain (MHC) gene, characteristic of adult soleus, is expressed in bulk hind limb muscle obtained from the 18-d rat fetus. We support these results by use of a monoclonal antibody (mAb) which is highly specific to the adult slow MHC. Immunoblots of MHC peptide maps show the same peptides, uniquely recognized by this antibody in adult soleus, are also identified in 18-d fetal limb muscle. Thus synthesis of slow myosin is an early event in skeletal myogenesis and is expressed concurrently with embryonic myosin. By immunofluorescence we demonstrate that in the 16-d fetus all primary myotubes in future fast and future slow muscles homogeneously express slow as well as embryonic myosin. Fiber heterogeneity arises owing to a developmentally regulated inhibition of slow MHC accumulation as muscles are progressively assembled from successive orders of cells. Assembly involves addition of new, superficial areas of the anterior tibial muscle (AT) and extensor digitorum longus muscle (EDL) in which primary cells initially stain weakly or are unstained with the slow mAb. In the developing AT and EDL, expression of slow myosin is unstable and is progressively restricted as these muscles specialize more and more towards the fast phenotype. Slow fibers persisting in deep portions of the adult EDL and AT are interpreted as vestiges of the original muscle primordium. A comparable inhibition of slow MHC accumulation occurs in the developing soleus but involves secondary, not primary, cells. Our results show that the fate of secondary cells is flexible and is spatially determined. By RIA we show that the relative proportions of slow MHC are fivefold greater in the soleus than in the EDL or AT at birth. After neonatal denervation, concentrations of slow MHC in the soleus rapidly decline, and we hypothesize that, in this muscle, the nerve protects and amplifies initial programs of slow MHC synthesis. Conversely, the content of slow MHC rises in the neonatally denervated EDL. This suggests that as the nerve amplifies fast MHC accumulation in the developing EDL, accumulation of slow MHC is inhibited in an antithetic fashion. Studies with phenylthiouracil-induced hypothyroidism indicate that inhibition of slow MHC accumulation in the EDL and AT is not initially under thyroid regulation. At later stages, the development of thyroid function plays a role in inhibiting slow MHC accumulation in the differentiating EDL and AT.(ABSTRACT TRUNCATED AT 400 WORDS)
Aging↗
Skeletal muscle ventricles in circulation. One to eleven weeks' experience.
Skeletal muscle ventricles were constructed from canine latissimus dorsi and connected to the thoracic aorta in six dogs. These ventricles were stimulated to contract synchronously during diastole. The skeletal muscle ventricles were capable of continuous stroke work when placed within the arterial circulation for several weeks. Effective synchronous diastolic counterpulsation was produced. These results demonstrate that diastolic counterpulsators can be constructed from skeletal muscle and in the future may provide a feasible therapeutic alternative for the treatment of end-stage cardiac failure.
Animals↗