Biomedical subjects

D Alling

Publications and source records attributed to D Alling.

13 recordsLinked to original sources

PubMed1999

Physiologic events initiating REM sleep in patients with the postpolio syndrome.

BACKGROUND: We previously studied the occurrence of muscle tone reduction (MTR), sawtooth waves (STW), and REM in sleep, and found a stereotypical sequence of these events in normal subjects. Patients with the postpolio syndrome may have involvement of the reticular formation in the brainstem, an area known to mediate initiation of REM sleep. We hypothesized that such brainstem pathology might affect the stereotyped sequence of events initiating REM sleep. METHODS: We measured the latencies to the onsets of the first MTR, the first STW, and the first REM in 13 patients with postpolio syndrome, 7 of whom had bulbar involvement. All latencies were calculated from the last body movement before the onset of REM sleep. RESULTS: Using analysis of variance, we found highly significant differences among the overall mean latencies of the three types of onset (MTR, STW, REM) and also between the mean latencies of the two subgroups of patients (bulbar, nonbulbar). Although the latencies for the entire group were longer than those of the normal volunteers, the differences were not significant. However, when the bulbar and nonbulbar groups were compared, analysis of variance showed significantly longer latencies for the bulbar group than for the nonbulbar group (p < 0.0001). The values for the nonbulbar patients closely resembled those for the normal controls. Although the latencies differed, the slopes of the regressions of REM on STW, STW on MTR, and REM on MTR resembled each other closely (p = 0.924). CONCLUSION: Prolongation of these latencies may be due to prolonged recruitment time for neurons in the pontine tegmentum, following damage from polio. This may be a sensitive marker of a brainstem lesion, and may also represent a type of sleep pathology not previously explored.

Aged↗

PubMed1997

Genetic analysis of experimentally induced lupus in mice.

The DBA/2 and C57BL/6 mouse strains, as well as the BXD RI lines derived from these strains, were used to map the genes controlling experimentally induced systemic lupus erythematosus (SLE). SLE was induced using two immunologic approaches: (1) immunization with the human monoclonal anti-DNA antibody expressing the 16/6Id, to which the DBA/2 strain is susceptible (responder) and the C57BL/6 strain is resistant (nonresponder); and (2) induction of autoimmune GVHD in B6D2F1 hosts by inoculation of parental DBA/2 (induces SLE) or C57BL/6 (does not induce SLE) T cells. By both approaches the BXD RI lines could be divided into distinct DBA/2-like and C57BL/6-like categories. Concordance of SLE induced by both methods was observed for susceptibility and resistance in 13/15 BXD lines (P < 0.005). The results suggest that at least two non-H-2 genes control susceptibility and resistance to experimentally induced SLE, one mapping to chromosome 7 and the other mapping to chromosome 14.

Animals↗

PubMed1994

Subunit interaction in B19 parvovirus empty capsids.

B19 parvovirus is a small single-stranded DNA virus with a genome that encodes only two structural proteins, designated VP1 and VP2. 60 copies of the structural proteins assemble into the viral capsid, with approximately 95% VP2 and 5% VP1. Recombinant empty capsids composed of VP2 alone or of VP2 and VP1 self-assemble into particles that are morphologically indistinguishable from full virions. Empty capsids containing both VP2 and VP1 elicit a strong neutralizing antibody response when used to immunize rabbits. Capsids containing only VP2 are similarly antigenic but elicit only weak neutralizing activity. We performed fine structure epitope mapping by measuring the reactivity of antisera raised against capsids composed of VP2 and VP1 or VP2 alone against 85 overlapping peptides spanning the sequence of the two structural proteins. A profile of the antigenic difference between empty capsids with and without VP1 was produced from the resulting data. This profile divided the sequence of the structural proteins into four regions that correlated well with expected viral structures. Thus, the addition of a small number of VP1 residues altered the antigenicity of the entire capsid. The major area of enhanced antigenicity is homologous to the spike of canine parvovirus, an area known to contain both neutralizing and host-range determinants. Our data are consistent with a model in which the unique region of VP1 is necessary for the virus to assume its mature capsid conformation.

Amino Acid Sequence↗

PubMed1991

Lack of efficacy of tranexamic acid in thrombocytopenic bleeding.

A controlled, randomized, double-blind study was performed to assess the effect of the oral antifibrinolytic agent tranexamic acid in patients with amegakaryocytic thrombocytopenia as regards their need for platelet transfusions and the number of bleeding episodes experienced. Each patient served as his or her own control and received sequential, randomized courses of either tranexamic acid or an identical placebo. The need for platelet transfusions due to bleeding and the total number of bleeding episodes were compared for tranexamic acid and placebo courses. Patients received platelet transfusions at the discretion of their personal physician and kept detailed records of bleeding episodes. Of three patients who completed the full study, none had a reduction in the need for platelet transfusions. Moreover, in the eight patients who participated in the study, there was no reduction in number of bleeding episodes during tranexamic acid treatment as compared to the number with placebo. Our data indicate that the prophylactic administration of tranexamic acid does not decrease dependence on platelet transfusions or decrease bleeding episodes in patients with bleeding due to amegakaryocytic thrombocytopenia.

Anemia, Aplastic↗

PubMed1989

A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy.

Although prednisone has been used to treat patients with idiopathic dilated cardiomyopathy, its efficacy has not been rigorously studied. We therefore randomly assigned 102 patients to either treatment with prednisone (60 mg per day) or a control group. At three months, improvement, defined prospectively as an increase in the ejection fraction of greater than or equal to 5 percentage points, was observed in 53 percent of the patients receiving prednisone and 27 percent of the controls (P = 0.005). The mean (+/- SE) ejection fraction increased 4.3 +/- 1.5 percentage points (from 17.9 +/- 1.0 to 22.2 +/- 1.6 percent) in the prednisone group, as compared with 2.1 +/- 0.8 percentage points (from 17.1 +/- 1.1 to 19.3 +/- 1.4 percent) in the control group (P = 0.054). All patients were categorized prospectively in two separately randomized subgroups. "Reactive" patients (n = 60) were those who had fibroblastic (n = 36) or lymphocytic (n = 2) infiltration or immunoglobulin deposition (n = 16) on endomyocardial biopsy, a positive gallium scan (n = 7), or an elevated erythrocyte sedimentation rate (n = 18). "Nonreactive" patients (n = 42) had none of these features. At three months, 67 percent of the reactive patients who received prednisone had improvement, as compared with 28 percent of the reactive controls (P = 0.004). Nonreactive patients did not improve significantly with prednisone (P = 0.51). After three months, reactive patients who received prednisone daily were switched to alternate-day therapy (60 mg every other day), and after six months the improvement seen earlier was no longer present. These data suggest that patients with idiopathic dilated cardiomyopathy may have some improvement when given a high dose of prednisone daily. However, the increases in the ejection fraction that we observed during prednisone treatment were small, their duration was limited, and the side effects were important. Overall, prednisone was judged to have only marginal clinical benefit, and should not be administered as standard therapy for dilated cardiomyopathy.

Cardiomyopathy, Dilated↗

PubMed1989

Differential non-responsiveness in humans of candidate Plasmodium falciparum vaccine antigens.

Synthetic subunit vaccines to sporozoites, merozoites, and gametes are being developed for malaria. The vaccine strategy assumes that the population to be immunized will respond favorably to these vaccine antigens. Using sera of 35 adults and 50 children from the The Gambia, West Africa, where Plasmodium falciparum is highly endemic, we examined the humoral immune response to candidate malaria vaccine antigens from sporozoites, merozoites, and gametes. We observed widespread restricted immunogenicity to defined parasite antigens in children and adults. HLA typing of adult lymphocytes demonstrated a marked diversity in HLA haplotypes in this population. Our results and those from our studies in mice suggest that genetic factors may partly explain the immunological non-responsiveness. This may necessitate re-evaluation of the malaria vaccine strategy.

Adult↗

PubMed1987

Determining the size of non-A, non-B hepatitis virus by filtration.

The approximate size of the H strain of non-A, non-B (NANB) hepatitis virus was determined by filtration through polycarbonate membranes. The accuracy and reproducibility of such filtrations were monitored by filtering selected reference viruses. These studies indicate that strain H, representative of the principal blood-borne NANB hepatitis virus, is 30-60 nm in diameter. It is therefore highly unlikely that NANB hepatitis virus is a retrovirus, as has been suggested.

Animals↗

PubMed1987

Large numbers of primitive stem cells are active simultaneously in aggregated embryo chimeric mice.

The possibility has been repeatedly raised that erythropoiesis results from clonal succession--the differentiation of one or a very small number of the most primitive stem cells that are sequentially activated to proliferate forming clones of differentiated cells and then eventually decline, to be replaced by new stem cell clones. We studied this possibility in chimeric mice made by combining embryos from two different strains so that they would have two distinct stem cell populations, each of which produces a different hemoglobin type (d and s). These were compared with F1 hybrids in which every stem cell produces both types. We measured the percentage of type d in seven to ten serial samples of circulating reticulocytes taken at three- to seven-day intervals and found that the variability in percent of this hemoglobin was only slightly higher in the chimeric mice than in F1 controls; SD ranged from 2.7% to 5.5% in the chimeric mice and from 3.4% to 3.9% in the controls. Using the binomial formula, the numbers of new clones formed during the reticulocyte life span, approximately three days, ranged from 33 to 118 in the individual chimeric mice. However, these numbers are underestimates because estimated numbers of clones depend inversely on variabilities, and the calculations did not exclude the contribution of experimental error to the overall variability. Total percentages of type d hemoglobin were also measured in seven to nine successive serial samples at 60- to 136-day intervals. These gave mean values similar to measures of newly synthesized hemoglobin in the same mice, but SD were larger, ranging from 5.3% to 8.4%. This reflects experimental error, both because of excess day-to-day variability found in this type of measurement and because there could not be fewer primitive stem cells activated to form clones of erythrocytes during the 45-day erythrocyte life span than during the three-day life span of reticulocytes. Since most and maybe all of the variation between successive samples in the same chimeric mouse appear to result from experimental error, many or even all of the primitive stem cells may simultaneously contribute to erythropoiesis.

Animals↗

PubMed1984

The effects of corticosteroids on mucous glycoprotein secretion from human airways in vitro.

In order to examine the mechanisms by which corticosteroids may benefit some patients with bronchorrhea, cultured human airways releasing [3H]glucosamine labeled mucous glycoproteins were exposed to corticosteroids, and mucus release was examined. Both dexamethasone and methylprednisolone produced dose-related suppression of the spontaneous release of radiolabeled mucous glycoproteins. The inhibitory effects of dexamethasone were maximal after 18 to 24 h and returned to control levels by 34 h. In order to study the effects of dexamethasone on stimulated mucus release, airways were exposed to dexamethasone and to the mucus secretagogues, histamine or 5-monohydroxyeicosatetraenoic acid. Both of these secretagogues stimulated radiolabeled mucous glycoprotein release from airways that had never been exposed to corticosteroids, as well as in a reduced fashion from corticosteroid-treated airways. The reduced mucus release caused by secretagogues from dexamethasone-treated airways appeared to reflect a lowered baseline secretion rate rather than a specific inhibition of either secretagogue.

Arachidonic Acids↗

PubMed1982

Heterogeneity of immunoregulatory T-cell subsets in systemic lupus erythematosus. Correlation with clinical features.

Immunoregulatory T-cell subsets as defined by differentiation antigens were studied in 32 patients with systemic lupus erythematosus (SLE) and 16 healthy persons using the monoclonal antibodies OKT 3 or anti-Leu 4 (T cells), anti-Leu 2a (suppressor/cytotoxic cells) and anti-Leu 3a (helper/inducer cells). Compared with the 95 percent confidence limits in control subjects, decreases or increases of Leu 3a+ cells were observed in 23 patients, whereas abnormal percentages of Leu 2a+ cells were observed in only 10 patients (p less than 0.002). The ratio of Leu 3a+ to Leu 2a+ cells varied over a much broader range (0.31 to 4.14) in patients with SLE than in control subjects (95 percent confidence limit 1.04 to 2.20). Furthermore, the helper:suppressor ratio correlated significantly (p less than 0.001) with a numerical clinical characterization of the patients. A low helper: suppressor ratio was observed in patients with severe renal disease, thrombocytopenia and onset of SLE by 20 years of age. Patients with a high helper:suppressor ratio had multisystem disease including lymphadenopathy, but only rarely SLE renal disease. Patients with a normal helper:suppressor ratio had the most widespread multisystem disease, often involving the kidneys and the central nervous system. The ratio was not correlated with duration of illness, disease activity or corticosteroid dosage in the patients examined. The study suggests that SLE is not one disease entity, but rather a symptom complex with different immunoregulatory abnormalities and associated manifestations.

Adult↗

PubMed1980

Comparison of four electrolyte instruments using the proposed NCCLS protocol for evaluation of precision and accuracy of automated instruments.

We compared four instruments, [Sequential Multiple Analyzer Computer (SMAC), AutoAnalyzer II (AAII), StatLyte and PVA-4] for the determination of Na, K, Cl and CO2 using the National Committee for Clinical Laboratory Standard's (NCCLS) protocol (PSEP-1) for evaluation of precision and accuracy of automated instruments. The protocol was applied concurrently to all four instruments. The repeatability results showed SMAC to have the highest precision among-days for K, Cl, and CO2 whereas StatLyte showed the highest precision among-days for Na. The PVA-4 had the best within-run precision for Na and Cl while the AAII and SMAC had the best within-run precision for K and CO2 respectively. Systematic biases among the instruments were small for Na and K. The AAII exhibited a nearly constant bias at all concentrations of Cl relative to the other three instruments. For CO2 the SMAC showed a large proportional bias compared with the other three instruments.

Autoanalysis↗

PubMed1980

Carriage rate of Staphylococcus aureus among patients receiving allergy injections.

The relative frequency of positive cultures for Staphylococcus aureus was studied among healthy young patients undergoing desensitization for allergies to determine whether the administration of repeated injections under aseptic conditions had any effect on the carriage rate of S. aureus. Three groups of patients were considered: group I, 11 patients receiving injections for the first time; group II, 20 patients already receiving injections; and group III, 20 control patients who did not receive any injections. Skin, nose and throat cultures were obtained once every two weeks for four months. Among group I patients the rate increased from 18% to 55% following the first injection, after which it fell to a 30-35% level. A rate of 25-35% was found in group II patients as compared to 15-20% in group III. Skin carriage of Staphylococcus aureus was found only among group I and group II patients. No local or systemic staphylococcal infections were found during the course of the study. The initial increase in carriage rate of staphylococcus among the healthy young adults in group I is unexplained. Thus, the results of this study further support our initial theory than regular use of needles alone increases the carriage rate of S. aureus, even under strict aseptic conditions.

Adult↗

PubMed1979

Severe malaria and glucose-6-phosphate-dehydrogenase deficiency: a reappraisal of the malaria/G-6-P.D. hypothesis.

Nigerian children with convulsions and Plasmodium falciparium parasitaemia above 100,000/microliter did not show a decreased frequency of glucose-6-phosphate-dehydrogenase (G.-6-P.D.) deficiency. A re-evaluation of earlier studies has led to the conclusion that clinical evidence of protection against falciparum malaria in G.-6-P.D.-deficient individuals is lacking. Evidence for the possible role of malaria in selecting for G.-6-P.D.-deficient genes consists solely of the geographical association of high frequencies of G.-6-P.D. deficiency with endemic malaria.

Child↗