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Biomedical subjects

J A Rollins

Publications and source records attributed to J A Rollins.

At least 19 recordsLinked to original sources

pH signaling in Sclerotinia sclerotiorum: identification of a pacC/RIM1 homolog.

Sclerotinia sclerotiorum acidifies its ambient environment by producing oxalic acid. This production of oxalic acid during plant infection has been implicated as a primary determinant of pathogenicity in this and other phytopathogenic fungi. We found that ambient pH conditions affect multiple processes in S. sclerotiorum. Exposure to increasing alkaline ambient pH increased the oxalic acid accumulation independent of carbon source, sclerotial development was favored by acidic ambient pH conditions but inhibited by neutral ambient pH, and transcripts encoding the endopolygalacturonase gene pg1 accumulated maximally under acidic culture conditions. We cloned a putative transcription factor-encoding gene, pac1, that may participate in a molecular signaling pathway for regulating gene expression in response to ambient pH. The three zinc finger domains of the predicted Pac1 protein are similar in sequence and organization to the zinc finger domains of the A. nidulans pH-responsive transcription factor PacC. The promoter of pac1 contains eight PacC consensus binding sites, suggesting that this gene, like its homologs, is autoregulated. Consistent with this suggestion, the accumulation of pac1 transcripts paralleled increases in ambient pH. Pac1 was determined to be a functional homolog of PacC by complementation of an A. nidulans pacC-null strain with pac1. Our results suggest that ambient pH is a regulatory cue for processes linked to pathogenicity, development, and virulence and that these processes may be under the molecular regulation of a conserved pH-dependent signaling pathway analogous to that in the nonpathogenic fungus A. nidulans.

Amino Acid Sequence↗

Minimizing the impact of community violence on child witnesses.

Child witnesses respond to violent events in two stages: an immediate reaction to the trauma followed by a response to the trauma and grief. The child's stage of development, circumstances surrounding the incident, and reactions of trusted adults affect responses. Secondary prevention measures during the first stage focus on protection and advocacy, while second stage interventions help the child acknowledge and tolerate the realities of the violent event. Child witnesses are at risk for posttraumatic stress disorder and other long-term social, emotional, and developmental problems. Individual characteristics, early life experiences, and protective factors in the environment contribute to children's resilience and ability to survive and grow into healthy adults.

Adolescent↗

Molecular characterization of the afl-1 locus in Aspergillus flavus.

An unusual mutation at the afl-1 locus, affecting aflatoxin biosynthesis in Aspergillus flavus 649, was investigated. The inability of strain 649 to produce aflatoxin was found to be the result of a large (greater than 60 kb) deletion that included a cluster of aflatoxin biosynthesis genes. Diploids formed by parasexual crosses between strain 649 and the aflatoxigenic strain 86 did not produce aflatoxin, indicating the dominant nature of the afl-1 mutation in strain 649. In metabolite feeding experiments, the diploids did not convert three intermediates in the aflatoxin pathway to aflatoxin. Northern (RNA blot) analysis of the diploids grown in medium conducive for aflatoxin production indicated that the aflatoxin pathway genes nor1, ver1, and omt1 were not expressed; however, there was low-level expression of the regulatory gene aflR. Pulsed-field electrophoresis gels indicated a larger (6 Mb) chromosome in strain 649 than the apparently homologous (4.9 Mb) chromosome in strain 86. The larger chromosome in strain 649 suggests that a rearrangement occurred in addition to the deletion. From these data, we proposed that a trans-sensing mechanism in diploids is responsible for the dominant phenotype associated with the afl-1 locus in strain 649. Such a mechanism is known in Drosophila melanogaster but has not been described for fungi.

Aflatoxins↗

A clinical therapeutic trial of cyclosporine in myasthenia gravis.

We randomly assigned 39 patients with steroid-dependent generalized myasthenia gravis to treatment with cyclosporine (5 mg/kg per body weight in divided doses) or placebo. Duration of treatment was 6 months. Patients were evaluated monthly. Primary measures of efficacy were quantified strength testing, antihuman acetylcholine receptor antibody titer, and dosage of corticosteroid medication. At the end of the study, patients in the cyclosporine group had significantly greater improvement in strength (p = 0.004) and a reduction in antireceptor antibody titer (p = 0.01). Percentage reduction of steroid medication was greater in the cyclosporine group, although the difference was not statistically significant (p = 0.12). There were no treatment failures, and there was one drug failure in the cyclosporine group. In the placebo group, there were three treatment failures. No significant nephrotoxicity was noted at this dosage during the first 6 months. During the subsequent 18 months of open-label therapy, continued reduction in steroid dosage occurred. Cumulative side effects, however, caused 35% of patients to discontinue the medication; 10% did so secondary to slowly progressive nephrotoxicity.

Adult↗

Cyclosporine-induced sympathetic activation and hypertension after heart transplantation.

BACKGROUND: Hypertension is a frequent complication of cyclosporine-induced immunosuppression, but the underlying mechanism is unknown. In anesthetized animals, the administration of cyclosporine increases sympathetic-nerve discharge, which may contribute to hypertension. METHODS: To determine whether cyclosporine-induced hypertension is accompanied by sustained sympathetic neural activation in patients, we recorded sympathetic action potentials using intraneural microelectrodes (in the peroneal nerve) in heart-transplant recipients receiving azathioprine and prednisone alone (n = 5) or in combination with cyclosporine (n = 14). We performed the same studies in eight patients with myasthenia gravis who were receiving cyclosporine and eight who were not, in five patients with essential hypertension, and in nine normal controls. RESULTS: Heart-transplant recipients receiving cyclosporine had higher mean arterial blood pressure (+/- SE) than those not receiving cyclosporine (112 +/- 3 vs. 96 +/- 4 mm Hg; P less than 0.05) and a 2.7-fold higher rate of sympathetic-nerve firing (80 +/- 3 vs. 30 +/- 4 bursts per minute; P less than 0.05). For patients with myasthenia gravis, similar doses of cyclosporine were associated with smaller elevations in mean arterial blood pressure (100 +/- 2 mm Hg, as compared with 91 +/- 4 mm Hg in those not receiving cyclosporine; P less than 0.05) and in the rate of sympathetic-nerve firing (46 +/- 3 bursts per minute, as compared with 25 +/- 4 bursts per minute; P less than 0.05). Sympathetic activity in patients with heart transplants or myasthenia gravis who were not being treated with cyclosporine was no different from that in patients with essential hypertension or in normal controls. CONCLUSIONS: Cyclosporine-induced hypertension is associated with sympathetic neural activation, which may be accentuated by the cardiac denervation that results from heart transplantation.

Action Potentials↗

Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporine in myasthenia gravis.

We randomly assigned 20 patients with progressively worsening generalized myasthenia gravis of recent onset whose illness was not controlled by anticholinesterase therapy to treatment with either cyclosporine (6 mg per kilogram of body weight per day) or placebo. Patients who had been treated with thymectomy, steroids, or other immunosuppressive agents were excluded. The duration of treatment was 12 months. Disease activity was assessed by quantified strength testing and by measurements of antihuman acetylcholine-receptor antibody. Patients were assessed at 6 months and 12 months, or at the following early end points: drug failure (doubling of creatinine), treatment failure (respiratory or swallowing difficulty), or protocol violation (stopping medication for more than five days). At six months, patients in the cyclosporine group had had significantly more objective improvement in strength; one early end point had been reached (drug failure; no treatment failures). In the placebo group, three early end points had been reached (all treatment failures). The decline in titers of acetylcholine-receptor antibody was larger in the treated group, although the difference was not statistically significant. At the end of the study (after 12 months of treatment or arrival at an earlier end point), improvement in strength and reduction in titers of anti-receptor antibody continued to be greater in the cyclosporine group. Nephrotoxicity occurred in three patients receiving cyclosporine but was nonprogressive with a reduction in dosage and reversible with discontinuation of the drug. These results are preliminary and need confirmation, but we conclude that cyclosporine is probably an effective therapy in some patients with myasthenia gravis.

Adult↗

Assessment of therapeutic plasmapheresis in demyelinating neurologic disorders.

Considerable controversy exists with regard to therapeutic efficacy of plasmapheresis in the immune-mediated demyelinating disorders of the peripheral and central nervous system: acute inflammatory polyneuropathy (Guillain-Barré syndrome), chronic inflammatory demyelinating polyneuropathy, and multiple sclerosis. In an effort to establish specific situations where plasmapheresis was of therapeutic value, we reviewed the experience at Southwestern Medical School, University of Texas Health Science Center at Dallas, and that published in the literature. In acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome), plasmapheresis may prevent progression of the illness, and it significantly increases the rate of recovery. For patients with chronic inflammatory polyneuropathy, plasmapheresis has produced clinical improvement in 50% of corticosteroid-refractory patients. The use of plasmapheresis in patients with acute or chronic progressive multiple sclerosis still remains controversial.

Adolescent↗

Childhood cancer: siblings draw and tell.

There is a growing awareness among health care professionals that the psychosocial needs of siblings of children with cancer are less adequately met than those of other family members. As part of a larger research study of 17 families of children with cancer, 20 healthy siblings, ages 3-11 years (7 males, 13 females), were tested using the Kinetic Family Drawing-Revised (Spinetta, McLaren, Fox, & Sparta, 1981) in one of two oncology clinics in a Southwestern state. Nine of the subjects participated in a sibling day. Data from the drawings and discussions with siblings confirm previous sibling research findings and reflect current social changes.

Art↗