Biomedical subjects
Publications and source records attributed to A Morrison.
This investigation of the differences between men's and women's attitudes toward war and endorsement of militaristic solutions to conflict counters the commonly held belief that men always endorse war more readily than do women. The present study reveals a more complex set of attitudes and responses, calls into question the findings of past research, and suggests directions for future study.
We have cloned the REV3 gene of Saccharomyces cerevisiae by complementation of the rev3 defect in UV-induced mutagenesis. The nucleotide sequence of this gene encodes a predicted protein of Mr 172,956 showing significant sequence similarity to Epstein-Barr virus DNA polymerase and to other members of a class of DNA polymerases including human DNA polymerase alpha and yeast DNA polymerase I. REV3 protein shows less sequence identity, and presumably a more distant evolutionary relationship, to the latter two enzymes than they do to each other. Haploids carrying a complete deletion of REV3 are viable. We suggest that induced mutagenesis in S. cerevisiae depends on a specialized DNA polymerase that is not required for other replicative processes. REV3 is located 2.8 centimorgans from CDC60, on chromosome XVI.
Fifty-four patients with acute lymphoblastic leukemia (ALL: 1 relapse, 21 high risk first complete remission (CR 1), 29 second CR (CR 2), and 3 third CR (CR 3) were treated by autologous bone marrow transplantation at three centers. Before storage, the marrows were purged ex vivo with appropriate MAbs RFAL3 (CD10), SB4 (CD19), and RFT2 (CD7), with rabbit serum as the source of complement. All patients received total body irradiation either 750 cGy (middose 15 cGy/min) as a single fraction or 6 x 200 cGy over 3 days (midline dose 16 cGy/min) with lung shielding from 1,100 cGy. The patients who received 750 cGy also received cyclophosphamide or the same drug combined with ara-C or prednisone, teniposide, vincristine, ara-C, and dauno-rubicin. Patients receiving 200 cGy x 6 also received either cyclophosphamide, melphalan, or ara-C and cyclophosphamide. Three patients died of post transplantation complications (interstitial pneumonia, hepatitis B liver necrosis, or encephalitis). This gives a procedure related mortality of 5%. Nonfatal complications were 10 cases of septicemia, 4 interstitial pneumonia, 2 interstitial nephritis, 1 veno-occlusive disease (VOD), and 1 case of hemolytic uremic syndrome. The patient autografted in relapse died of relapse within 2 months. In CR 1 6 or 21 patients have had a relapse, and the actuarial leukemia free survival from CR is 65% (median follow-up 16 months). In CR 2-3 18 of 32 patients have relapsed, and the actuarial leukemia free survival is 31% (median follow-up 18.5 months) from CR. Twelve patients have achieved an inversion, (i.e., present CR longer than previous CR), with a further seven with the potential to achieve inversion. We conclude that ABMT in high risk ALL has a low procedure related mortality (5%), and there are few other complications. The in vitro purging with MAbs had no adverse effect on bone marrow reconstitution, but this study was not designed to demonstrate its antileukemic efficacy. The actuarial leukemia free survival time in the present study for patients with high risk CR 1 and the inversions in CF 2-3 are promising and indicate a potential beneficial effect of ABMT.
Between 1978 and 1982, 205 anencephalic infants weighing more than 2,500 g were born alive in California. Although typically none were offered significant support, almost 9% lived more than one week. It seems reasonable to assume that modern intensive care would have increased survival times dramatically. In fact, preliminary data from centers specializing in neonatal organ transplantation demonstrate that seven to 14 days of ventilatory support can be accomplished for anencephalic infants without occurrence of brainstem death. Given these data and medical information that clearly establishes anencephalic infants as a "special case" of children who have not suffered brain death but could reasonably be used as organ donors, we believe that parents who wish to do so should be allowed to continue ventilatory support for their anencephalic children for whatever period of time is necessary to find organ recipients and arrange for organ donation. Arbitrary cutoff points for intensive care and artificial criteria for brain death should not be necessary to allow the use of anencephalic infants as organ donors. We believe that current laws should be changed to permit this scenario.
The RAD6 gene of Saccharomyces cerevisiae, which is required for normal tolerance of DNA damage and for sporulation, encodes a 172-residue protein whose 23 carboxyl-terminal residues are almost all acidic. We show that this polyacidic sequence appends to RAD6 protein as a polyanionic tail and that its function in vivo does not require stoichiometry of length. RAD6 protein was purified to near homogeneity from a yeast strain carrying a RAD6 overproducing plasmid. Approximately the first 150 residues of RAD6 protein composed a structural domain that was resistant to proteinase K and had a Stokes radius typical of a globular protein of its calculated mass. The carboxyl-terminal polyacidic sequence was sensitive to proteinase K, and it endowed RAD6 protein with an aberrantly large Stokes radius that indicates an asymmetric shape. We deduce that RAD6 protein is monomeric and comprises a globular domain with a freely extending polyacidic tail. We tested the phenotypic effects of partial or complete deletion of the polyacidic sequence, demonstrating the presence of the shortened proteins in the cell by using antibody to RAD6 protein. Removal of the entire polyacidic sequence severely reduced sporulation but only slightly affected survival after UV irradiation or UV-induced mutagenesis. Strains with deletions of all but the first 4 or 15 residues of the polyacidic sequence were phenotypically almost wild type or wild type, respectively. We conclude that the intrinsic activity of RAD6 protein resides in the globular domain, that the polyacidic sequence has a stimulatory or modifying role evident primarily in sporulation, and that only a short section apparently functions as effectively as the entire polyacidic sequence.
Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.
Previous studies have demonstrated alterations in plasma free fatty acid content in Reye's syndrome (RS). We have therefore studied erythrocyte membrane lipids to determine if there are concomitant structural and functional modifications attributable to RS. Erythrocyte lipids were measured in children with RS and in critically ill children also requiring intensive care (ICU). In comatose RS patients erythrocyte phospholipid arachidonate was increased 2-fold relative to control ICU patients: 20.46 +/- 2.14 versus 10.41 +/- 2.32% of total erythrocyte phospholipid, p less than 0.05. RS coma patients also demonstrated an increased ratio of erythrocyte phospholipid polyunsaturated/saturated fatty acids (0.76 +/- 0.10) compared to ICU controls (0.48 +/- 0.08, p less than 0.05). Erythrocyte cholesterol was higher in RS patients (79.00 +/- 6.61 micrograms/mg protein) than in ICU controls (59.74 +/- 6.09, p less than 0.05). Erythrocyte malondialdehyde generation was decreased in comatose RS patients (404 +/- 28 nmol malondialdehyde/g hemoglobin) versus ICU (517 +/- 29, p less than 0.05). Although plasma vitamin E was depressed in RS patients, the erythrocyte vitamin E concentrations were no different in RS patients than in ICU patients. All RS patients had a typical viral prodrome and either a history of aspirin intake and/or measurable serum salicylate on admission. All of the biochemical abnormalities in RS patients listed above returned to values comparable to those of healthy RS siblings on recovery. The transient nature of these phenomena suggests that they were related to viral infection and/or aspirin rather than to intrinsic differences in lipid metabolism between RS patients and controls.
In recent years there has been a dramatic increase in the number of patients transferred to public hospitals in the United States. We prospectively studied 467 medical and surgical patients who were transferred from the emergency departments of other hospitals in the Chicago area to Cook County Hospital and subsequently admitted. Eighty-nine percent of the transferred patients were black or Hispanic, and 81 percent were unemployed. Most (87 percent) were transferred because they lacked adequate medical insurance. Only 6 percent of the patients had given written informed consent for transfer. Twenty-two percent required admission to an intensive care unit, usually within 24 hours of arrival. Twenty-four percent were in an unstable clinical condition at the transferring hospital. The proportion of transferred medical-service patients who died was 9.4 percent, which was significantly higher than the proportion of medical-service patients who were not transferred (3.8 percent, P less than 0.01). There was no significant difference in the proportion of deaths on the surgical service between patients who were transferred and those who were not (1.5 vs. 2.4 percent). We conclude that patients are transferred to public hospitals predominantly for economic reasons, in spite of the fact that many of them are in an unstable condition at the time of transfer.
Peripheral blood and/or bone marrow lymphoblasts from 25 patients with acute lymphoblastic leukemia (ALL) were tested with a panel of monoclonal antibodies (MoAbs) and conventional hematopoietic markers by three different laboratories. The results were analysed to evaluate the reproducibility of ALL phenotype determinations. Specimens were transported between laboratories by 24-h courier service and were classified on the basis of indirect immunofluorescence MoAb reactivities as follows: B-lineage ALL (BA-1+T-MCS-2-); T-lineage ALL (T+BA-1-MCS-2-); myeloid antigen ALL (MCS-2+BA-1-CALLA-T-) and unclassified ALL (BA-1-MCS-2-CALLA-T-). Conventional marker studies for surface immunoglobulin (sIg), cytoplasmic immunoglobulin (cIg), sheep erythrocyte rosette formation (E) and nuclear terminal deoxynucleotidyl transferase (TdT) were also performed. In the cases with sufficient marker data to permit classification, 90% (18/20) were identically classified by different laboratories and this concordance was statistically significant (p less than 0.05). The agreement between laboratories for individual MoAb and conventional marker analyses was statistically significant (p less than 0.05) for all markers with the exception of BA-2, cIg and TdT determinations. Six of 7 discordant BA-2 cases represented BA-2+ evaluations which had subsequent BA-2- results following specimen transportation. These findings suggest instability of the BA-2 antigen to transport conditions. A similar pattern of positive to negative evaluations following transportation was observed in 5/5 discordant results involving other MoAbs. Disagreement between laboratories for cIg and TdT determinations implies that the detection of cytoplasmic or nuclear antigens may be more prone to subjective interpretation than cell surface antigen marker analyses. Our findings suggest that immunofluorescence marker studies employing MoAbs to cell surface antigens are in general highly reproducible. Our results also indicate that specimen storage conditions and the cellular location of target antigens are important variables which may affect the reproducibility of ALL phenotype determinations.
The role of the alpha 2-adrenergic system in regulating prolactin release has been studied in vivo in male rats. Yohimbine administration alone, at doses ranging from 0.2 to 5.0 mg/kg, resulted in a dose-related elevation of plasma prolactin levels from a basal level of 8 +/- 2 to 65 +/- 6 ng/ml at the highest dose. In the same experiment clonidine, 0.2 mg/kg, suppressed basal prolactin levels to 4 +/- 1 ng/ml and returned prolactin levels of all animals receiving 0.2-5.0 mg/kg yohimbine to basal levels. Rats were treated with increasing doses of clonidine (0.05-1.0 mg/kg) in the presence or absence of a constant dose (1.0 mg/kg) of yohimbine. Clonidine alone at doses of 0.05 and 0.2 mg/kg again significantly suppressed prolactin levels, while a dose of 1.0 mg/kg did not (failure of high dose clonidine to suppress prolactin levels suggests an additional effect of clonidine on prolactin secretion unrelated to alpha 2-adrenergic agonist action). All three doses of clonidine completely reversed yohimbine-induced prolactin release. Basal prolactin levels were also significantly reduced by the selective alpha 2-adrenergic agonist UK-14,304 at a dose of 0.2 mg/kg. Yohimbine-induced prolactin release was reversed by UK-14,304 at doses of 0.2 and 1.0 mg/kg, but not at the lowest dose studied, 0.05 mg/kg. The lower potency of UK-14,304 than clonidine in this assay is consistent with the lower potency of UK-14,304 as an alpha 2-adrenergic-agonist antihypertensive agent. Several alpha 2-antagonists in addition to yohimbine were studied.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in human urine is considered to be a reflection of renal prostacyclin production. Because of the large amounts of unidentified eicosanoid metabolites in urine that may potentially bind to 6-keto-PGF1 alpha antisera, most radioimmunoassays include chromatographic purification of urine. A comparison of chromatographic techniques and of antisera to 6-keto-PGF1 alpha for the assay of human urine is described. Gas chromatography--negative-ion chemical-ionization mass spectrometry (GC--NICI-MS) was used as the reference method. Radioimmunoassays were performed with each of four antisera combined with each of three chromatographic purification systems (silicic acid, Sephadex LH-20, reversed-phase high-performance liquid chromatography). There was marked variability in the results; however, there was at least one chromatographic method for each antiserum that yielded results comparable to GC--NICI-MS. Direct radioimmunoassay of urine without chromatography yielded markedly elevated and variable results for the four antisera. In contrast, the four antisera gave very similar results with direct assay of media from isolated perfused organs. Thus, for the radioimmunoassay of 6-keto-PGF1 alpha in human urine, each antiserum is sensitive to different contaminants in urine and must be individually matched to a chromatographic purification system.
Ablation of greater than 70% of renal mass in the rat results in hypertension, proteinuria, and glomerular sclerosis of the remnant kidney. Rats with a remnant kidney have increased excretion of thromboxane in the urine when compared with normal rats. Chronic oral administration of OKY 1581, an inhibitor of thromboxane synthesis, in rats with a remnant kidney increases renal blood flow and glomerular filtration rate (GFR), decreases protein and thromboxane excretion in the urine, lowers blood pressure and cardiac index, and improves renal histology. The degree of hypertrophy of the remnant kidney was unaffected by administration of OKY 1581. Calculated values for single nephron plasma flow and GFR were significantly greater in rats with remnant kidneys given OKY 1581 than in rats given saline. Acute i.v. administration of OKY 1581 increased renal plasma flow and GFR in rats with a remnant kidney but not in normal rats or rats with a remnant kidney previously treated with acetylsalicyclic acid. OKY 1581 markedly inhibited platelet aggregation. We suggest that in this model of renal disease platelet aggregation and intraglomerular thrombosis play a key role in the development of glomerulosclerosis. Inhibition of platelet aggregation prevents development of glomerulosclerosis, hypertension, and cardiac hypertrophy. We suggest that hyperperfusion and hyperfiltration per se occurring in remnant glomeruli are not directly responsible for the development of glomerulosclerosis.
We have compared the anti-inflammatory efficacy of 5% tolmetin sodium dihydrate, 0.5% prednisolone disodium phosphate, and 0.1% betamethasone disodium phosphate in 71 consecutive patients presenting with acute endogenous non-granulomatous uveitis randomly assigned to one of these treatment groups. Inflammatory symptoms and signs were scored during the course of the 21-day trial period. There was no statistically significant difference in the effect on the signs or symptoms of the three drugs tested. 90% of the Betnesol (betamethasone sodium phosphate, benzalkonium chloride) treated group were clinically judged cured compared with 68% of the Predsol (prednisolone sodium phosphate, benzalkonium chloride) treated group, and 57% of the tolmetin treated group.
An unabridged series of 73 thumb amputations subjected to replantation or revascularization surgery in the years 1971 to 1980 has been examined in detail as a combined prospective and retrospective study to determine the factors playing a role in survival and failure. The causes of failure and complications are demonstrated. The overall failure rate was 27%. The factors influencing the outcome were: the injury--mechanical type and degree of amputation; the patient--age and amputation level; and the surgeon--frequency of utilization of vein grafts. The highest failure was seen in the complete amputation with avulsion/diffuse crush injury group (63%). Incomplete amputations had the lowest failure rate, particularly if the injury type was guillotine/local crush and at a level proximal to the metacarpophalangeal joint. Patients aged 11 to 20 years had a low failure rate (18%) whereas children under 5 years had a high failure rate (40%). Arterial thrombosis was the most frequent complication and cause of failure. The surgeon could modify the result by frequent use of vein grafts for arterial reconstruction and by reoperation for thrombotic complication. Five thumbs failed to revascularize at the primary operation and were removed at this primary operation.
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DNA gyrase supercoils DNA by passing one DNA segment through another by means of a reversible double-strand break at specific DNA sites. We determined the nucleotide sequence of two highly preferred gyrase binding sites and analyzed the grip of gyrase on the DNA by using protection from nuclease attack. The DNA-breakage site of gyrase was centered in about 50 base pairs (bp) of DNA that was completely protected from DNase I and flanked by DNA regions cut at average intervals of 9.9 bases. The same pattern of protection from DNase I was observed with topoisomerase II', an enzyme that shares structural homology with gyrase. The gyrase site of DNA breakage was off-center in the 140 bp of DNA protected from exonuclease III digestion. ATP or inhibitors of gyrase had little specific effect on DNase I protection. On addition of a nonhydrolyzable analogue of ATP, previously stable barriers to exonuclease III were invaded and new barriers appeared. We discuss a detailed model uniting these results with previous data on gyrase structure and mechanism.