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Biomedical subjects

S Palmer

Publications and source records attributed to S Palmer.

At least 163 records · Page 9Linked to original sources

Control of forelimb muscle activity by populations of corticomotoneuronal and rubromotoneuronal cells.

We review and synthesize evidence on the activity of corticomotoneuronal (CM) and rubromotoneuronal (RM) cells and single motor units in forearm muscles in monkeys performing alternating wrist movements. The CM and RM cells were identified by post-spike facilitation of rectified forelimb EMG activity. RM cells facilitated more muscles per cell (mean: 3.0 of 6 synergist muscles) than CM cells (2.4/6). Both groups had "reciprocal" cells which also suppressed antagonists of their facilitated target muscles. Unlike CM cells, some RM cells cofacilitated flexor and extensor muscles (5.8 or 12 muscles). During performance of a standard ramp-and-hold force tracking task the firing patterns of CM and RM cells, as well as single motor units, fell into distinct response types. Each population had phasic-tonic and tonic cells. Unique to the CM population were cells whose discharge increased during the static hold period; unique to RM cells were bidirectionally responsive and unmodulated neurons. Many motor units showed decrementing discharge. To estimate the ensemble activities of these populations the response histograms of different cells were summed (with force ramps aligned) in proportion to the relative frequency of each cell type. The population response histogram of CM cells was phasic-tonic, consistent with the predominant response type. The population response of RM cells was also phasic-tonic, but showed a shallower phasic modulation relative to discharge that was sustained during both directions of movement. The population histogram of motor units of a muscle was proportional to the average of rectified multiunit EMG, and typically exhibited decrementing activity during the static hold. The effects of excitatory postsynaptic potentials (EPSPs) on firing probability of motoneurons previously documented in intracellular studies are combined with the mean firing rates in the population histograms and the known amplitudes of CM-EPSPs and RM-EPSPs to infer the relative contributions of the supraspinal cells to tonic discharge of active motoneurons. This analysis suggests that for intermediate levels of force, the CM cells would increment motoneuron discharge by about 9 impulses/second (i.p.s.) and RM cells by about 2.4 i.p.s. The analysis also reveals differences in the population activity of CM and RM cells compared to their target motoneurons, which may be due to other input cells and to recruitment properties of motoneurons.

Animals↗

HTLV-1 infection in Papua New Guinea: evidence for serologic false positivity.

Serum samples from 557 individuals participating in studies from four separate lowland and highland populations in Papua New Guinea exhibited consistently false-positive results for human T lymphotropic virus (HTLV) type 1 (10%) and human immunodeficiency virus (HIV) type 1 (5%) antibody in direct antiglobulin and agglutination assays. All serum samples were negative in competitive ELISAs and radioimmunoassays for HTLV-1 and HIV-1; selected samples of reactive sera were negative in an HTLV-2 competitive ELISA. Immunofluorescent antibody tests using HTLV-1 infected cells correlated poorly with ELISA results. None of the sera from Papua New Guinea neutralized vesicular stomatitis virus pseudotypes of HTLV-1. By Western blot analysis, only three serum samples were weakly reactive to HTLV-1 gag proteins. These studies suggest there is as yet no firm evidence of HTLV-1, HTLV-2, or HIV-1 infection in Papua New Guinea, although there may be a low prevalence.

Acquired Immunodeficiency Syndrome↗

Bone marrow transplantation for severe aplastic anaemia using cyclosporin: long-term follow-up.

Between 1980 and 1986 we transplanted 49 patients from genotypically identical sibling donors for severe aplastic anaemia (SAA). Patients were predominantly adults, median age 22 years (3-47). Forty-six were multiply transfused prior to referral. The median pre-transplant disease duration was 4 months (1-72). Pre-transplant conditioning was with cyclophosphamide (CY) 200 mg/kg. Cyclosporin A (CSA) was given from 1 day before the transplant and continued for 9-12 months. Eight of 48 evaluable patients did not achieve initial engraftment (early graft failure). Six of these episodes occurred in the eight cases transplanted more than 1 year after diagnosis, four of whom died. Thirteen of 44 (30%) evaluable patients (with stable engraftment after one or two transplants) had grade III-IV acute graft-versus-host disease (GVHD). Only three of 35 patients surviving more than 100 days with sustained engraftment developed generalized chronic GVHD; two died. An additional 10 patients developed localized chronic GVHD, which was very mild, transient and related to CSA withdrawal. Four long-term survivors are known to have autologous marrow function. All survivors have Karnofsky scores of greater than 90%. We conclude that the use of CSA after bone marrow transplantation for SAA is associated with good long-term survival and minimal on-going chronic GVHD. Early graft failure was frequent when transplantation was delayed beyond 1 year from diagnosis.

Anemia, Aplastic↗

Regulation of in vitro translation by double-stranded RNA in mammalian cell mRNA preparations.

Polyadenylated mRNA has been purified from a variety of human and mouse cell sources. These preparations are actively translated in the wheat germ cell-free system but have only poor ability to stimulate the nuclease-treated reticulocyte lysate. The translation of endogenous and exogenous globin mRNA is strongly inhibited by the poly(A)+ RNA preparations in reticulocyte lysates. Both polysomal and non-polysomal RNA have similar effects but poly(A)+ RNA is almost 2000-fold more inhibitory than poly(A)-RNA on a weight basis. The inhibition is abolished in the presence a high concentration of poly(I).poly(C). Analysis of endogenous eIF-2 in the lysate reveals that the subunit becomes extensively phosphorylated in the presence of the inhibitory poly(A)+ RNA. Prolonged incubation of lysate with poly(A)+ RNA also causes some nucleolytic degradation of polysomal globin mRNA. These characteristics suggest that some eukaryotic cell mRNAs contain regions of double-stranded structure which are sufficiently extensive to activate translational control mechanisms in the reticulocyte lysate.

Animals↗

Postnatal changes in lung phospholipids and alveolar macrophages in term newborn monkeys.

In order to better understand the postnatal sequence of surfactant secretion and establishment of the alveolar macrophage (AM) population in newborn primates, healthy Macaca nemestrina monkeys were sacrificed during fetal life at term gestation (n = 5), or at 2 days (n = 5) or 3-4 weeks (n = 5) after term vaginal delivery. Excised lung tissue and left lung lavage were analyzed for phospholipid (PL) content, surface active material (SAM) extract, PL components, surface activity, pressure-volume characteristics, and AM number. Compared to term fetal animals, 2 day old term newborn monkeys were found to have a several-fold increase in lavage PL and SAM, and this was associated with greater maximal lung volume and drier lungs, but not improved deflation stability. During the subsequent 3-4 weeks of life, a 42% reduction in lung tissue stores of PL and SAM, and an 87% reduction in lavage PL and SAM were noted. Despite these major changes in quantity, there were relatively minor changes in the composition of the PL synthesized and released. The reduced quantity of SAM in the 3-4 week old animals led to a small decline in deflation stability. The several-fold increase in lavage PL and SAM during the first 2 days of life was accompanied by a 33-fold increase in AM; there was an additional 4-fold increase in AM number by 3-4 weeks of age. The abundance of lavage surfactant at 2 days of age may play a role in the influx of AM.

Animals↗

Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study.

Single fraction radiotherapy can be used effectively to palliate painful bone metastases. The optimal single dose of radiotherapy required for pain relief is unknown. Twenty-six patients have been treated with a single fraction of 4 Gy to the site of the bone pain. Partial pain relief was seen in 9/21 (5%). Response occurred within 3 weeks of radiotherapy. These results question the mechanism of pain relief following radiotherapy and suggest a method of pain control using single repeatable low dose treatments.

Aged↗

Reference frame effects on shape perception in two versus three dimensions.

Three experiments are reported in which it is tested whether the Gestalt effect of configural orientation on shape perception operates on two-dimensional (2-D) or three-dimensional (3-D) representations of space. It is known that gravitationally defined squares and diamonds take longer to discriminate in diagonal arrays than in horizontal or vertical arrays. In the first experiment it is shown that this interference effect decreases dramatically in magnitude when pictorial depth information is added so that subjects perceive the target shapes in different depth planes. In the second experiment this difference is shown not to be due to relative size of the target shapes or to occlusion of a background plane. It is also shown, in the final experiment, that this difference is not due to linear perspective information or merely to perception of the target figures in a 3-D scene. The overall pattern of results supports the position that this configural reference frame effect arises primarily when the elements of the configuration are coplanar, and that the principal organization underlying it is the structure of the perceived 3-D environment rather than that of the 2-D image. In all three experiments, however, there is also a small interference effect in the noncoplanar 3-D conditions. This might be due either to some aspect of reference frame selection operating on the 2-D image representation or to the failure of subjects to see depth in the 3-D stimuli on some proportion of the trials.

Attention↗

A prospective comparative study of the extended nonstress test and the nipple stimulation contraction stress test.

The nonstress test and the nipple stimulation contraction stress test were performed at the Medical College of Georgia and the University of Mississippi Medical Center, with the use of common maternal state protocols, minimum criteria for baseline fetal heart rate reactivity, and follow-up of abnormal test results. At the Medical College of Georgia, 656 patients were studied with nonstress tests used as the primary test, whereas at the University of Mississippi Medical Center, 614 patients were managed with the nipple stimulation contraction stress test used as the primary test. Both populations were comparable in regard to pregnancy complications, gestational age, birth weight, perinatal outcomes, cesarean section rates, and the incidence of positive contraction stress tests. Specificity and positive and negative predictive values were similar for both tests. The extended nonstress test had higher sensitivity but also required significantly longer mean duration of testing. The corrected perinatal mortality rate for a reactive nonstress test or negative nipple stimulation contraction stress test was zero within one week of the last test. We conclude that both tests provide excellent primary methods of fetal surveillance and that the decision to use one test rather than the other should be made on the basis of considerations of cost, convenience, time availability, and the presence of specific test contraindications or pregnancy complications.

Breast↗

Dietary considerations for risk reduction.

In the last two decades, the potential role of dietary factors in the etiology and prevention of cancer has gained considerable attention. Using an in-depth assessment performed in 1982 by the National Research Council's (NRC) Committee on Diet, Nutrition, and Cancer as the basis, this paper compares dietary guidelines to lower cancer risk issued by the NRC committee with those of other major scientific and voluntary health organizations in the United States and abroad. In general, the public has been advised to decrease total fat intake, maintain appropriate body weight, emphasize consumption of certain fruits and vegetables and complex carbohydrates, and to drink alcohol only in moderation. The guidelines proposed by the National Cancer Institute, the American Cancer Society, and the NRC committee are in agreement with those made in Japan and some European countries, and are similar to those proposed for health promotion by the United States Departments of Agriculture and Health and Human Services. Individual scientists and organizations have both criticized and endorsed these guidelines. Additional research to strengthen the data base and better agreement among scientists about the criteria for acceptability of evidence are needed for arriving at more definitive dietary recommendations to the public.

American Cancer Society↗

The labelling of polyphosphoinositides with [32P]Pi and the accumulation of inositol phosphates in vasopressin-stimulated hepatocytes.

When hepatocytes were incubated with [32P]Pi, the kinetics for the labelling of the monoester phosphate groups of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate were similar to each other and slightly slower than that for the labelling of the gamma-phosphate of ATP. Analysis of the water-soluble 3H-labelled materials derived from [3H]inositol-labelled hepatocytes revealed that, in addition to inositol and its mono-, bis- and tris-phosphates (Ins, InsP, InsP2 and InsP3), these cells contained two unidentified radioactive compounds which co-eluted with InsP on anion-exchange chromatography. When [3H]inositol-labelled hepatocytes were stimulated with 0.23 microM-vasopressin in the presence of 10 mM-Li+, there was an accumulation of radioactivity in InsP, InsP2 and InsP3 but not in Ins or the two unidentified compounds. Further analysis of these inositol phosphates by h.p.l.c. revealed that vasopressin also stimulates the accumulation of inositol tetrakisphosphate (InsP4) in these cells. Vasopressin-stimulated InsP and InsP2 accumulations were maximal in the presence of 1-10 mM-Li+ but InsP3 accumulation continued to increase up to 50 mM-Li+. Accumulated inositol phosphates were retained within the cell. Li+ from 1 to 50 mM did not influence the extent of vasopressin-stimulated inositol lipid degradation in hepatocytes. In the absence of Li+, radioactivity in vasopressin-stimulated hepatocytes accumulated almost entirely in free inositol. The vasopressin-stimulated accumulation of inositol phosphates in the presence of 10 mM-Li+ was abolished by a V1-vasopressin antagonist. Inositol phosphate accumulation was not influenced by ionophore A23187, dimethyl sulphoxide or indomethacin.

Adenosine Triphosphate↗

The role of non-nutritive dietary constituents in carcinogenesis.

Very low levels of a large variety of non-nutritive chemicals occur in the diet. Among those that occur naturally are metabolites of molds (for example, mycotoxins) and bacteria (for example, nitrosamines) and natural constituents of plants (for example, pyrrolizidine alkaloids). Many of these are occasional contaminants, whereas others are normal components of relatively common foods. Some compounds (for example, aflatoxin, nitrosamines, and hydrazones) have been found to be carcinogenic in laboratory animals and mutagenic in bacterial and other systems, thereby posing a potential risk to humans. However, there have been very few definitive epidemiologic studies. Therefore, further investigations are necessary to determine the significance of these experimental findings for humans. It is apparent that many foods naturally contain substances with mutagenic properties and that some substances found in foods can enhance or inhibit the mutagenic activity of other compounds. Furthermore, mutagens can be formed during the cooking or processing of foods. However, caution is needed in the interpretation of these findings. Although mutagens by definition are "suspect" carcinogens, many mutagens detected in foods have not been adequately tested for carcinogenicity, and therefore their significance for human health cannot be fully assessed. With the exception of studies on non-nutritive sweeteners like saccharin and cyclamate, or those on nitrate and nitrite, very few epidemiologic studies have been conducted to examine the effect of food additives on cancer risk. Of the few direct food additives that have been tested and found to be carcinogenic in animals, all except saccharin have been banned from use in the food supply. Minute residues of a few indirect additives that are known either to produce cancer in animals (for example, vinyl chloride and acrylonitrile) or to be carcinogenic in humans (for example, vinyl chloride) are occasionally detected in foods. Thus far, the increasing use of food additives does not seem to have contributed significantly to the overall cancer risk for humans. However, the relatively short duration of use of many of these substances and the inadequacy of the data base preclude definitive conclusions. Very low levels of a large and chemically diverse group of substances--environmental contaminants (for example, residues of pesticides, polycyclic aromatic hydrocarbons, and traces of toxic metals)--may be present in foods.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Surfactant quantity and composition during recovery from hyaline membrane disease.

The appearance of phosphatidylglycerol in the tracheal wash of infants with hyaline membrane disease (HMD) has been reported to be associated with clinical signs of recovery. We analyzed lung tissue and bronchoalveolar lavage surfactant in an animal model of HMD to determine whether phosphatidylglycerol or some other component is necessary for recovery. The amount and composition of phospholipid (PL) was determined in the premature Macaca nemestrina monkey (140 days' gestation) during an acute stage of HMD, and in two stages of recovery. These changes were compared to observations made in healthy premature controls (140 days), gestational age-matched fetuses (140 days), and fetuses of 150 days' gestation (term = 168 days). The amount of PL and its surfactant composition in lung homogenates of the right lower lobe and in lavage of the excised left lung was determined. Compared to 140-day fetuses, the healthy controls had a several-fold increase in lavage PL and disaturated phosphatidylcholine (DSPC) during the first few days of life (p less than 0.05). Prior to recovery, animals with HMD had no such increase in lavage PL or DSPC and demonstrated poor deflation stability. Recovery was associated with increased tissue and lavage PL (p less than 0.05) and increased fractions of phosphatidylinositol and DSPC (p less than 0.05), but not phosphatidylglycerol. The tissue compositional changes observed during recovery reflected maturational changes observed in the fetal animals studied at 10 days' greater gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differential response of normal rat mammary epithelial cells to mammogenic hormones and EGF.

A simple dissociation procedure and the collagen gel culture system have been utilized to determine the effects of mammogenic hormones and epidermal growth factor (EGF) on the proliferation of normal rat mammary epithelial (RME) cells in serum-free culture. Epithelial fragments, isolated from normal virgin F344 rat mammary glands by enzyme digestion followed by Percoll density gradient centrifugation, were embedded within a rat tail collagen matrix. A three- to four-fold increase in cell number was observed when ovine prolactin (PRL) and progesterone (P) were present in the basal medium during 7 days of culture. Mouse EGF stimulated one cell doubling during the same culture period. Isolated mammary organoids produced a 'stellate' type colony when PRL + P were present in the culture medium. These colonies were composed of small, tightly packed cuboidal cells. The addition of EGF to the basal medium produced a diffuse 'basket' type colony which was composed of large, elongate cells. When the complete hormonal and growth factor combination (PRL + P + EGF) was present, a 'mixed' type colony was observed which contained both the large and small epithelial cell types. Immunocytochemical analysis revealed that both the cuboidal and elongate cells present in the two colony types stained with antibodies to keratin indicating that these cells were epithelial in nature. The small cuboidal cells also expressed thioesterase II and alpha-lactalbumin, both specific for secretory mammary epithelial cells. The large, elongate cell type, however, was positive for actin but did not stain for either secretory epithelial specific marker. The results reported here suggest that normal rat mammary tissue may contain two epithelial populations, one which responds to PRL + P and the other which responds to EGF.

Animals↗

Cyclosporine and graft failure following bone marrow transplantation for severe aplastic anaemia.

Thirty-nine patients with severe aplastic anaemia were transplanted from HLA identical sibling donors. Irradiation was not used in the pre-transplant immunosuppressive protocol and cyclosporine was used as the post graft immunosuppressive agent. The incidence of primary graft failure (no take) was low occurring in 3/38 evaluable patients. Late graft failure 4-7.5 months post BMT occurred in five patients and was associated with withdrawal of cyclosporine therapy. Mixed lymphocyte chimaerism was demonstrated in 3/5 cases at the time of late graft failure and subsequent marrow recovery was autologous in four patients. Mortality from graft failure was low with 2/38 evaluable patients (5%) dying from this complication.

Adolescent↗

Pyoderma gangrenosum in myelodysplasia and acute leukaemia.

Pyoderma gangrenosum is a rare occurrence in patients with haematological malignancy. This characteristic but nonspecific inflammatory process with skin destruction occurred in 4 patients with myelodysplasia, in one with acute leukaemic transformation of myelofibrosis, and in de novo acute myeloblastic leukaemia in another. Clinically, the cutaneous lesion in these patients differed from that associated with inflammatory bowel disease, arthritis, or the idiopathic type of pyoderma gangrenosum by having the vesiculo-bullous borders. Histopathological differences were also evident since more superficial layers of the skin were involved in the ulceration than typically encountered in patients with non-malignant systemic disease. Despite the less penetrating nature of this variant, treatment of the pyoderma gangrenosum is unsatisfactory and in the absence of effective therapy for the underlying disease, healing occurred only in the patient with acute leukaemia who achieved complete remission in response to chemotherapy.

Acute Disease↗

Changes in lung volume and deflation stability in hyaline membrane disease.

Total lung capacity (TLC), inspiratory capacity, functional residual capacity, and deflation stability of prematurely delivered Macaca nemestrina primates were measured serially during development of, and recovery from, hyaline membrane disease (HMD) to relate changes in lung volumes to changes in deflation stability. Gestational age-matched primates that did not develop HMD served as controls. TLC, measured by N2 washout, fell at 2-12 h of age (P less than 0.0001) in animals with HMD and remained lower than controls for at least 48 h (P less than 0.005). However, deflation stability, defined as the fraction of TLC remaining upon deflation to 10 cm H2O, improved from 2 to 12 h of age (P less than 0.001). Postmortem studies confirm the measurements of TLC and deflation stability and provide evidence that interstitial thickening and obstruction of air spaces with debris may be partially responsible for the observed changes in TLC in primates that develop HMD. It has been assumed that TLC is reduced in HMD because of atelectasis from elevated alveolar surface tension, but the sequential measurements in these animals suggest that other mechanisms also contribute.

Animals↗