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Biomedical subjects

R E Allen

Publications and source records attributed to R E Allen.

At least 73 records · Page 4Linked to original sources

Xanthine oxidoreductase is present in human synovium.

It is postulated that the mobile inflamed joint may be subject to cyclical ischaemic reperfusion injury. Xanthine oxidoreductase is an enzyme thought to contribute to oxidative reperfusion injury, and the detection of this activity in human synovium is described. Three normal and five rheumatoid tissues were assayed with a carbon-14 radioassay detecting the conversion of [14C]xanthine to [14C]uric acid. Rheumatoid synovia contained 0.67-305 microU/g tissue (n = 5), while normal synovia contained 1.2-5.0 microU/g tissue (n = 3).

Allopurinol↗

Interaction of ovine somatomedin and multiplication stimulating activity/rat insulin-like growth factor II with cultured skeletal muscle satellite cells.

The interactions of 125I-multiplication stimulating activity (MSA) and 125I-ovine somatomedin with receptors on skeletal muscle satellite cells are described. Specific binding of 125I-MSA/rIGF-II was inhibited by MSA/rIGF-II and oSm but not by insulin. Binding of 125I-oSm was inhibited by MSA/rIGF-II, oSm and insulin. In addition, 24-h pre-incubation of satellite cells with insulin increased the amount of 125I-MSA/rIGF-II bound, but insulin concentrations below 550 micrograms/l had no effect on the subsequent binding of 125I-oSm. Preincubation of cultures with oSm or MSA/rIGF-II decreased the subsequent binding of 125I-oSm and 125I-MSA/rIGF-II. These preliminary experiments suggest that oSm is similar to IGF-I in its binding characteristics and that primary cultures of skeletal muscle satellite cells possess type I and type II IGF receptors.

Animals↗

Cognitive disabilities: measuring the social consequences of mental disorders.

The disabilities associated with psychiatric illnesses can be separated into six cognitive levels that can be identified by functions the patient is able to perform, by the types of assistance required to compensate for dysfunctions, and by the social dysfunction observed in home and work environments. These cognitive levels can be used to measure the severity of mental disorders; changes in these levels reflect temporal changes in severity that are consequent to treatment and/or natural history of the condition. These cognitive levels can also be used to assess need for hospitalization and/or community placement, readiness for discharge from hospital, and effectiveness of treatment. A collaborative relationship between occupational therapists and psychiatrists is needed for the most effective use of these reliable and objective assessments of cognitive function levels in patients with psychiatric illness.

Activities of Daily Living↗

Muscle cell culture as a tool in animal growth research.

Muscle cell culture techniques have been used for several years in research on muscle growth and development. Several types of culture systems have been devised, including primary cultures from embryonic or postnatal muscle and myogenic cell lines. In addition, serum-free and serum-containing media have been developed to address specific muscle development questions. Many of these questions center around muscle cell differentiation and muscle cell physiology; and, more recently, muscle cell cultures have been used as bioassay tools for examining growth physiology in domestic animals. In our laboratory, skeletal muscle satellite cells have been studied in vitro to evaluate the effect of several protein hormones and growth factors on satellite cell proliferation and differentiation. Of the hormones examined, only the insulin-like growth factors/somatomedins and fibroblast growth factor have been shown to have a stimulatory effect on proliferation that could be physiologically significant. None of the major anterior pituitary hormones interacted directly with satellite cells to stimulate proliferation. With advances in serum-free medium formulations and cell separation techniques, more information can be obtained from experiments with muscle cell cultures. With appropriate design and interpretation, our knowledge of muscle growth in domestic animals will be expanded.

Age Factors↗

Satellite cell proliferation in response to pituitary hormones.

Proliferation of rat skeletal muscle satellite cells was studied in vitro, and their ability to respond to a variety of protein hormones was examined, including: growth hormone, prolactin, luteinizing hormone, thyrotropin and fibroblast growth factor. All experiments were conducted in serum-free medium to avoid complicating interactions with serum constituents such as other hormones or binding proteins. Dose-response curves were constructed for each protein and encompassed the physiological range plus concentrations two to three orders of magnitude greater than the physiological range. Of the proteins examined, the only one shown to have the ability to directly stimulate satellite cell proliferation was fibroblast growth factor. None of the anterior pituitary protein hormones had the ability to interact directly with satellite cells to stimulate proliferation in vitro. Therefore, satellite cells seem to be selective in their response to protein hormones, and the classes identified thus far are hormones in the insulin-like growth factor family and fibroblast growth factor. These two classes of protein hormones are quite different and would not be expected to act through a common pathway. Consequently, we have proposed a dual regulatory system that may allow for local as well as systemic stimulation of satellite cells.

Animals↗

Atropine and glycopyrrolate as ECT preanesthesia.

Twenty-four patients receiving ECT were systematically studied to compare the effects of two dosages of atropine and two dosages of glycopyrrolate as preanesthetic agents. Glycopyrrolate resulted in more cardiac arrhythmias, nausea and vomiting, and episodes of bradycardia than atropine (p = .4). More patients receiving atropine showed post-ECT confusion, but the clinical impact of this was minimal. Atropine appears to be preferable to glycopyrrolate for use in ECT preanesthesia.

Adolescent↗

A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma.

The pharmacokinetics of isolated limb perfusion were studied to see what melphalan concentrations were achieved and how effective the isolation was. Twenty-eight patients received 32 limb perfusions with heat and melphalan for locally recurrent or level V melanoma. Melphalan was given 0.75 mg/kg for axillary/popliteal or 1.2 mg/kg for femoral perfusions with heat (perfusate 42 degrees C, limb 40 degrees C) for 1 hour. Melphalan concentratives were measured by high-performance liquid chromatography in seven patients. Peak perfusate melphalan concentrations were 6.1 to 115 mg/ml, which was one to two logs higher than peak systemic concentratives of melphalan. Isolation of the perfusate circuit from the systemic circulation was better for axillary and popliteal perfusions than for femoral perfusions (P less than 0.05). Complete responses were seen in 81% of evaluable patients; long-term local control was achieved in most patients, although many developed hematogenous metastases. Toxicity included erythema and edema in all, mild leukopenia in two, neuropathy in two, and amputation was required in one patient. Improvements in surgical technique include regional anesthesia to reduce vasospasms and transcutaneous measurement of fluorescein to measure leak. Perfusion with heat and melphalan remains the treatment of choice for in-transit metastases from melanoma.

Chemotherapy, Cancer, Regional Perfusion↗

A serum-free medium that supports the growth of cultured skeletal muscle satellite cells.

A serum-free medium has been devised that supports the proliferation and differentiation of primary cultures of rat skeletal muscle satellite cells for up to 4 d. The medium consists of a mixture of Dulbecco's modified Eagle's medium and MCDB-104 plus insulin, dexamethasone, pituitary fibroblast growth factor, Deutsch fetuin, and linoleic acid. In addition to promoting the formation of myotubes from satellite cells, a decrease in fibroblast contamination of these cultures was observed when cultures grown in serum-free medium were compared to cultures grown in serum-containing medium.

Animals↗

Ovine somatomedin, multiplication-stimulating activity, and insulin promote skeletal muscle satellite cell proliferation in vitro.

Primary cultures of skeletal muscle satellite cells, the postnatal myogenic precursor cells, were induced to proliferate by exposure to physiological levels of somatomedins (Sms)/insulin-like growth factors (IGFs) and pharmacological levels of insulin. These polypeptides were included in medium containing horse serum as well as serum-free defined medium. Dexamethasone inclusion in the serum-containing medium facilitated the ovine Sm (oSm; P less than 0.05) and the multiplication-stimulating activity/rat IGF-II (MSA/rIGF-II; P less than 0.25) responses, but not the insulin proliferative response. In addition, data from defined medium studies indicate that satellite cells are more sensitive to both IGF moieties than insulin and that the proliferations induced by half-maximal concentrations of oSm and insulin were similar (P less than 0.05), but both were different from the proliferation induced by MSA/rIGF-II (P less than 0.05). In the presence of insulin concentrations that promote maximum proliferation, the addition of oSm did not produce an additive effect, whereas the addition of MSA/rIGF-II did produce a significant increase in satellite cell proliferation above that induced by insulin. MSA/rIGF-II may, therefore, be stimulating proliferation of satellite cells through a receptor system different from that serving insulin and oSm. Collectively, these data support the hypothesis that Sms/IGFs play an important role in the control of postnatal muscle growth by providing a link between these hormones and one of the significant target cells involved in this process.

Animals↗

Muscle growth and satellite cell proliferative activity in obese (OB/OB) mice.

Muscle growth of male obese (ob/ob) and lean mice at 2, 3, 5 and 8 wk were analyzed on the basis of weights of gastrocnemius, plantaris and soleus muscles from each hind leg. The carcasses (prepared by removing skin, viscera, head, feet and tail) were analyzed for fat content so that the effect of phenotype on the relationship between muscle weight and fat-free carcass weight could be assessed. For each age group the obese mice had less muscle relative to fat-free carcass weight than lean mice, with the difference being significant at 3 wk (P less than .05) and 8 wk (P less than .025). The proliferative activity of muscle satellite cells in 2- and 3-wk-old obese and lean mice was measured on isolated muscle fibers by autoradiography. Muscle fiber diameter and number of nuclei/unit length were unaffected by phenotype, but the proportion of muscle nuclei showing proliferative activity was lower (P less than .01) in obese than in lean mice at 2 wk (1.05 vs 1.93%, respectively) and 3 wk of age (.23 vs .59%, respectively). These results are consistent with the suggestion that muscle growth is limited by satellite-cell proliferative activity, although direct evidence for a cause and effect relationship is not provided.

Adipose Tissue↗

Effect of insulin and linoleic acid on satellite cell differentiation.

Differentiation of rat skeletal muscle satellite cells was studied in vitro. Linoleic acid and insulin, two unrelated compounds that reportedly stimulate differentiation of other types of myogenic cells, were used to examine the regulation of differentiation in satellite cell cultures. As in cultures of chick embryo muscle cells, linoleic acid stimulated fusion but only at low serum concentrations or in defined medium without fibroblast growth factor (FGF). The effects of insulin on differentiation were quite variable, however; at very low cell densities no stimulatory effect was observed. In intermediate and, to a lesser extent, high density satellite cell cultures, the addition of insulin at concentrations between .01 and 1.0 microM stimulated satellite cell fusion. Whenever increases in fusion were observed, however, a parallel increase in cell number was also found. A closer examination of the relationship between differentiation and the presence or absence of mitogenic agents in the medium suggested that a mitogenic signal and the resultant proliferation of cells prevented differentiation. Subsequent experiments indicated that fusion could be induced by lower serum concentration or by removal of FGF, as long as linoleic acid was present in the medium. Therefore, proliferation and differentiation appear to be antagonistic processes in cultured satellite cells. If the rate of proliferation is depressed, either by mitogen removal or by increasing cell density, differentiation is favored. Differentiation can, therefore, be regulated and applied to in vitro studies of satellite cell activity.

Animals↗

Developmental comparisons of boars and barrows: I. Growth rate, carcass and muscle characteristics.

The rate of gain, carcass measurements and three muscles were evaluated in 65 crossbred boars representing 13 litters that were allotted at 4 wk of age to slaughter weight and treatment groups as follows: 1) 105 kg, castrated; 2) 105 kg, intact; 3) 118 kg, intact; 4) 132 kg, intact and 5) 145 kg, intact. One barrow and four boars within a litter constituted a replicate and each replicate was penned separately. The growth rate of all boars to 105 kg constituted one group and was compared with the growth rate of barrows to 105 kg live body weight. Average daily gain from 4 wk until 105 kg did not differ significantly between boars and barrows. Growth rate of the boars continued at an increasing rate until they reached 87.3 kg live weight, while maximum daily gain of barrows occurred at 76.3 kg live weight or 11 kg less than that of boars. At 105 kg, boars had 31.3% less 10th rib backfat thickness and 2.9% greater carcass length than barrows, but longissimus muscle area did not differ. Barrows had greater backfat thickness at 105 kg than 145-kg boars. As live weight increased from 105 to 145 kg, carcass length, 10th rib backfat thickness and longissimus area of boars increased (P less than .01) linearly. Fat-free muscle weights of the brachialis (BR), semitendinosus (ST) and longissimus (L) did not differ between boars and barrows at 105 kg. Boars at 105 kg had 1.3 and 1.7% more moisture in the BR and ST, respectively, than barrows. Percentage protein, total intramuscular fat and fiber diameter in the BR, ST and L muscles did not differ between boars and barrows at 105 kg or with increasing live weight in boars. Total RNA increased linearly (P less than .05) in the BR and ST as boars increased in live weight from 105 to 145 kg.

Adipose Tissue↗

Developmental comparisons of boars and barrows: II. Body composition and bone development.

Differences in total carcass bone, muscle and fat, and linear measurements of the tibia and radius were evaluated in barrows at 105 kg and boars at 105, 118, 132 and 145 kg live body weight. The carcasses of five replicates were physically separated into skin, bone and soft tissues, and the linear measurements of the tibia and radius were obtained on seven replicates. At live weight of 105 kg, boars did not differ significantly in fat-free muscle, but they had 33.2% less fat, 11% greater bone weight and 14% greater skin weight than barrows. At 145 kg, boars had total carcass fat weight comparable with 105-kg barrows. Fat-free muscle, bone and skin weight of boars increased at linear rates of .41, .083 and .104 kg/kg of body weight increase from 105 to 145 kg, respectively. At 105 kg, density and length of the tibia and radius did not differ between boars and barrows. The tibia of boars were heavier than those of barrows at 105 kg, resulting in a greater ratio of tibia weight to length (indirect measure of bone thickness). As boars increased in live weight from 105 to 145 kg, total weight and length of the tibia and radius increased linearly. The ratio of weight to length of the tibia and radius increased during this 40-kg weight gain, indicating that weight of both bones increased at a greater rate than length. These results indicate that boars and barrows have the same weight of total carcass fat when boars are 40 kg heavier than the barrows. The greater bone weight of boar carcasses compared with barrows is due to greater bone thickness.

Adipose Tissue↗

Regulation of skeletal muscle satellite cell proliferation by bovine pituitary fibroblast growth factor.

Satellite cells in skeletal muscle have been implicated in muscle growth processes and regeneration. However, very little is known about the regulation of their proliferation and differentiation. The effect of fibroblast growth factor (FGF) on the proliferation of myogenic cells from adult rat skeletal muscle, presumably satellite cells, has been examined, and FGF has been found to be a potent mitogen for these cells. The mitogenic properties of serum were also documented and studied in conjunction with FGF. Even under conditions of maximal stimulation by serum, the addition of FGF caused a substantial increase in proliferation of satellite cells. The additive nature of the FGF and serum-stimulatory activity suggests that FGF-like molecules are not the active agents in serum and that more than one pathway may be involved in stimulating satellite cell proliferation.

Animals↗

Dexamethasone suppression in depressed elderly outpatients.

The dexamethasone suppression test (DST) was performed as part of the preliminary workup in 85 previously untreated outpatients with major affective disorder, unipolar depressive type, who were over age 60. All patients were given a systematic structured interview (NIMH-DIS), and all had scores over 20 on the 21-item Hamilton Depression Rating Scale (HAM-D). Only 12 patients (14%) had positive DSTs; more of the non-melancholic (6 of 25; 24%) than melancholic (6 of 60; 10%) patients failed to suppress serum cortisol following standard dexamethasone challenge (p less than .10). DST results did not correlate with patients' HAM-D or Zung depression scores, gender, response to treatment, or any other variable studied. These findings suggest that, in comparison to previous reports, a positive DST may be 1) less common in major depressive disorders, 2) no more common in more severely depressed patients, and 3) less relevant to indications for specific treatment.

Aged↗

Costing out a wage and benefit package.

Labor costs represent the largest single cost of operation for most organizations. For the unionized employer, the compensation package is determined during contract negotiations. It is important for both union and management negotiators to be able to identify the cost of a proposed agreement. Both parties to a contract should know whether a proposed compensation package is consistent with an organization's ability to pay. In addition, when "trading" demands, both parties should be aware of the cost of the demands being traded. An approach to costing out a labor agreement has been presented in this article. While it can be described as the standard approach, it is subject to several criticisms. Typically, it is applied in a way that assumes that history will repeat itself. In addition, it focuses on the direct cost of a proposed compensation package. While this is certainly relevant, the impact of the compensation package on organization profits is more important. Finally, the time value of money is not taken into account. This would be important if a multi-year contract is being negotiated. While there are legitimate concerns about the approach presented here, our objective is to provide the reader with a basic approach to costing out a wage and benefit package. Anyone involved in contract negotiations or, in the nonunion firm, anyone responsible for administering a wage and benefit program, should be aware of the problems that we have described and seek out reference materials to provide guidance in addressing them.

Costs and Cost Analysis↗

Effect of growth hormone, testosterone and serum concentration on actin synthesis in cultured satellite cells.

Because most of the DNA in a mature muscle accumulates during postnatal life and is derived from satellite cells, cellular regulation of protein accumulation in muscle fibers originating from satellite cells is an important aspect of muscle growth control. These experiments were designed to study the modulation of a alpha-actin accumulation in satellite cell-derived myotubes by serum and two anabolic hormones commonly assumed to be involved in muscle growth regulation; growth hormone and testosterone. Satellite cells were cultured from rats ranging in age from 5 d to 1 yr. After fusion into myotubes, various levels of pig serum, 3 to 20%, were added to culture medium, and the amount of alpha-actin per myotube nucleus was determined 4 d later. The quantity increased with increasing percentages of serum in the medium. For an assessment of the extent to which serum stimulatory activity was due to growth hormone or testosterone in the serum, similar experiments were conducted with medium containing 10% pig serum plus various levels of porcine growth hormone or testosterone. Neither of these hormones stimulated actin accumulation at concentrations from 10(-9) to 10(-6) M, a range encompassing physiological levels for each hormone. These experiments do not support the premise that either growth hormone and (or) testosterone are the blood-borne agents that interact directly with muscle to stimulate protein accretion, because neither growth hormone nor testosterone acted directly on muscle cells in vitro to stimulate muscle protein accumulation.

Actins↗