Biomedical subjects

S A Johnson

Publications and source records attributed to S A Johnson.

At least 163 records · Page 9Linked to original sources

PubMed1988

Selective reduction of mRNA for the beta-amyloid precursor protein that lacks a Kunitz-type protease inhibitor motif in cortex from Alzheimer brains.

In poly(A) RNA from cerebral cortex obtained postmortem from victims of Alzheimer's disease (AD), an alternatively spliced mRNA for the amyloid precursor protein (APP-695 mRNA) was shown to be decreased by 65%. Another form (APP-751 mRNA) with an additional exon encoding a Kunitz-type (serine) protease inhibitor motif did not change appreciably (less than 30% decrease) in AD cortex. If this twofold increase in the APP-751 mRNA/APP-695 mRNA ratio results in a corresponding increase in the APP-751/APP-695 protein ratio, this would support the hypothesis that impaired proteolysis promotes the accumulation of abnormal proteins in the brain during AD. In the two previously known, major alternatively spliced forms of ca. 3.3 and 3.5 kb, we resolved doublet RNAs for each form that are consistent with sequence data showing multiple polyadenylation sites (J. Kang et al., 1987, Nature (London) 325, 733-736.). Smaller APP-related transcripts were also found (1.1, 1.0, 0.8, and 0.3 kb), some of which are selectively altered in AD.

Alzheimer Disease↗

PubMed1988

A concave annular array design, based on phasor summation--Part I: Design methodology.

A detailed method for the design of annular arrays based on phasor summation is developed. The net phase shift across each annulus obtained by phasor summation is a very important factor in the design of an annular array, and determines the strength of the signal received. The method presented in this paper allows the designer to evaluate the trade-offs in parameters such as the strength of the signal from each annulus, the efficiency of each annulus, and the depth of focus that would be achievable. A concave annular array has been fabricated according to this design method. A set of graphs are given for an actual design to illustrate how one may readily evaluate these trade-offs.

Equipment Design↗

PubMed1988

A concave annular array design, based on phasor summation--Part II: Beam profiles and resultant images by B-scan and synthetic focus methods.

A brief review of the synthetic focusing method is given. The theoretical limit of resolution that may be achieved with the synthetic focusing methods is demonstrated using experimental results on a thin thread obtained with an annular array whose design was given in Part I. The advantage of large aperture arrays is illustrated by an in vitro reflection image of a dog artery, made with this array, that has at least four times the spatial resolution of present clinical B-scanners operating in the same frequency range.

Animals↗

PubMed1988

Alterations in uterine epithelial tight junction structure during the oestrous cycle and implantation in the pig.

The structure of the pig uterine epithelium tight junction has been studied using freeze-fracture methods during oestrus and implantation. Compared with non-pregnant non-cyclic pigs, in both pregnancy and during the cycle the number of intersections per unit area of the tight junction ridges increases to a maximum 16 days after ovulation. There was no significant alteration in the depth or number of ridges in the tight junction band. The only significant difference between tight junctions in cyclic and pregnant pigs was a brief increase in the depth during the cycle (12-15 days after ovulation). The number of intersections is thought to be a far more important measure than depth in determining the permeability of the tight junction. It therefore seems unlikely that changes in tight junction structure play any direct role in the rescue of the corpus luteum or in establishing pregnancy but merely reflect the alterations in progesterone concentrations. However, the decrease in uterine permeability indicated by the increase in intersection frequency has been reported for other species and may reflect an important change in the uterine milieu in preparation for a possible pregnancy, apparently induced by alterations in progesterone concentration.

Animals↗

PubMed1988

Treatment of acute myeloid leukaemia with early intensive induction therapy.

Patients with primary acute myeloid leukaemia were treated with induction therapy consisting of daunorubicin 50 mg/m2 (days 1 and 2) and continuous cytosine arabinoside 400 mg/m2 (days 1-5) with a 7-10-day gap between courses. Consolidation therapy consisted of one further similar course and a final course of cytosine 1 g/m2 infusion (days 1-5). Patients were randomised to receive no further treatment or monthly maintenance therapy consisting of thioguanine 100 mg/m2 twice daily and etoposide 100 mg/m2 twice daily (days 1-5) alternating with CCNU 50 mg/m2 once to a total of 6 courses. 64 patients entered the study; median age was 54 years (range 18-74 years) and 51 patients entered complete remission (79.7%). Thirty-two patients completed consolidation and were randomised between maintenance therapy (n = 16) and no treatment (n = 16). 21 patients have relapsed with neither remission duration nor relapse rate being affected by maintenance therapy.

Adult↗

PubMed1988

Liposome-encapsulated hemoglobin: oxygen binding properties and respiratory function.

Lipid bilayer membranes have been used to encapsulate hemoglobin and organic phosphates, resulting in a synthetic red cell with oxygen-binding properties very similar to red blood cells (RBCs). In addition to the oxygen-binding parameters, we report here an improvement in the lipid formulation that confers upon the liposome-encapsulated hemoglobin (LEH) a circulation retention half-time of 15 to 20 hours in mice. Cooperative oxygen binding of the encapsulated hemoglobin is retained and the oxygen-binding affinity can be maintained at or below the level of fresh whole blood for many weeks by co-encapsulation of an appropriate concentration of pyridoxal-5-phosphate. A comparison of the kinetics of oxygen exchange across the membranes of the synthetic red cells and RBCs indicates that the increased surface to volume ratio of the much smaller synthetic red cells, coupled with their somewhat lower concentration of hemoglobin, results in more rapid rates of oxygen uptake and release than are seen with RBCs. Efficacy studies have begun and we report here the successful transfusion of rats with LEH. After greater than 90% exchange, LEH transfused rats were able to maintain activity with normal respiratory and cardiac function parameters.

Animals↗

PubMed1987

Rapid screening with indirect immunotoxin for monoclonal antibodies against human small cell lung cancer.

For the first time, a screening procedure for antitumor monoclonal antibodies (MOABs) has been developed in which the ability of MOABs to mediate the indirect action of another immunotoxin is the primary criterion for selection of hybridomas for expansion and cloning. Use of the indirect immunotoxin makes it possible to screen MOABs for cytotoxic potential without the necessity of covalently coupling toxin to each individual MOAB. Hybridomas derived from spleens of immunized mice were screened for the synthesis of monoclonal antibodies able to participate in the delivery of a pharmacologically active, indirect immunotoxin conjugate to H69 lung cancer cells. The indirect immunotoxin conjugate was goat anti-mouse immunoglobulin disulfide linked to pokeweed antiviral protein. There was no correlation between the results of the screening with the indirect immunotoxin and an enzyme-linked immunosorbent assay screen for binding of MOAB to tumor cell membranes. An indirect immunotoxin prepared from Fab' fragments of goat anti-mouse immunoglobulin was also effective as an indirect immunotoxin conjugate. Each screening of more than 300 hybridomas was performed in 3 days. The indirect immunotoxin screen detected antitumor MOABs which were not detected by the conventional enzyme-linked immunosorbent assay method. A MOAB selected by the indirect immunotoxin screen was conjugated to pokeweed antiviral protein; the conjugate mediated immunocytotoxicity in a standard direct toxicity assay.

Animals↗

PubMed1987

Isolation of the insoluble straight fibrils of Pick's disease.

This paper describes the isolation and partial purification of the straight fibrils that occur in the neurons of Pick's disease. Pick fibrils are highly insoluble in a variety of solvents. These fibrils were shown to be sodium dodecyl sulfate insoluble even in the presence of a reducing agent at elevated temperatures. This allowed the selective isolation of the fibrils using the SDS boiling procedure and sucrose gradient centrifugation that have been described for isolation of paired helical filaments of Alzheimer's disease. The isolated fibrils retained the native morphology seen in tissue sections, but some appeared to become unraveled to yield a paired helical appearance. These results indicate that the Pick fibrils have many chemical and structural characteristics in common with Alzheimer paired helical filaments, and suggest that these two diseases may be closely related.

Aged↗

PubMed1986

Extensive postmortem stability of RNA from rat and human brain.

The postmortem stability of brain RNA was measured in rat and human samples for up to 48 hr. Whole rat brains, cooled at a rate approximating that of human brains awaiting autopsy, were collected at intervals from 0 to 48 hr after death and frozen. These samples were compared with freshly obtained, unfrozen rat brains. Two potentially independent characteristics of these RNA populations were measured: the recovery or yield of RNA/gram tissue (quantity) and the integrity or extent of degradation (quality). Total RNA yields were similar after all postmortem delays. Hybridization of [32P]-labeled cDNA probes to nitrocellulose filter blots of electrophoretically separated rat brain RNA failed to reveal degradation of the specific rat brain mRNAs during the postmortem period. Similarly, in vitro translation of these same rat total RNA samples produced high molecular weight translation products with no differences between long and short postmortem times. Human cerebral cortex RNA was prepared by the same methods as those used for rat brain from a neurosurgical sample and four other donors with postmortem intervals from 7 to 36 hr. Typically, the yield of total RNA from human brain was 40-50% of the yield from rat brain. When analyzed by RNA gel blot hybridization studies, as for rat brain RNA, human cortical RNA appeared slightly degraded. However, the degree of apparent RNA degradation was not related to the postmortem interval. In vitro translation products of human cortical RNA revealed high molecular weight peptides at all postmortem intervals, but slightly less [35S]incorporation into these bands was found at the longer postmortem intervals relative to the shorter times. Together, these results demonstrate an extensive stability of brain RNA that invites aggressive use of molecular genetic techniques for the study of human neurodegenerative diseases.

Animals↗

PubMed1986

Adult acute lymphoblastic leukaemia: a study of prognostic features and response to treatment over a ten year period.

Between 1974 and 1984 69 adults with acute lymphoblastic leukaemia (ALL) were treated with two different protocols. Fifty-four (78%) of the patients entered complete remission (CR); 27 of these then received a consolidation protocol consisting of daunorubicin, cytosine arabinoside and 6-thioguanine, followed by two courses of intravenous methotrexate 500 mg m-2 with folinic acid rescue. All patients received intrathecal methotrexate and cranial irradiation (24 Gy) followed by maintenance therapy with 6-mercaptopurine and methotrexate for at least 2 years. The median survival for all patients was 23 months from the time of presentation with an actuarial 5-year survival of 21%. The actuarial chance of surviving 5 years in CR for patients receiving the consolidation protocol was 38% compared to 19% for patients receiving no consolidation (P = NS). Only patient age and white cell count at presentation were found to influence the chance of achieving CR and the chance of overall survival. The presence or absence of c-ALL antigen did not influence prognosis. Patients younger than 35 years with low white cell counts at presentation (less than 10 X 10(9)1(-1] had a particularly good prognosis but no patient with T-ALL and no patient older than 50 years old at diagnosis survived more than 18 months.

Adolescent↗

PubMed1985

Ventricular fibrillation during coronary angiography: reduced incidence in man with contrast media lacking calcium binding additives.

The intracoronary injection of contrast media during coronary angiography occasionally results in ventricular fibrillation. Experimental studies have implicated the calcium sequestering agents, sodium citrate and EDTA in Renografin 76 (RG76), as contributing to this complication. Angiovist 370 (AV370) is a contrast medium similar to RG76 except that it contains disodium calcium EDTA instead of EDTA and sodium citrate. To determine if contrast media lacking sodium citrate and EDTA will result in a lower incidence of ventricular fibrillation in man, this investigation compared the incidence of contrast media-induced ventricular fibrillation in patients undergoing coronary angiography with RG76 to that with AV370. Group A consisted of 2,500 consecutive patients undergoing coronary angiography with RG76 and group B consisted of 2,000 subsequent consecutive patients in whom AV370 was employed as the contrast medium. There was no significant difference between groups A and B with respect to the volume of contrast media used per patient (153 +/- 49 ml vs 154 +/- 45ml), age (58.4 +/- 10 vs 58.6 +/- 10 years), sex (70% male vs 70% male), ejection fraction (59 +/- 17 vs 60 +/- 20), history of mitral valve disease (5.8% vs 7.1%), history of aortic valve disease (6.7% vs 6.5%), prior coronary artery bypass graft surgery (6.6% vs 7.3%), or extent of coronary artery disease. Fifteen episodes of contrast media-induced ventricular fibrillation occurred in group A (incidence 0.6%) whereas two episodes occurred in group B (incidence 0.1%) (p less than 0.02). Each patient was successfully defibrillated and no adverse sequelae resulted. Thus the present investigation suggests that the incidence of ventricular fibrillation during coronary angiography can be significantly decreased by using contrast media lacking sodium citrate and EDTA.

Aged↗

PubMed1985

Evolutionary conservation of DNA sequences expressed in sea urchin eggs and early embryos.

DNA sequence divergence measurements indicate that Strongylocentrotus franciscanus is more distinct from S. purpuratus and S. drobachiensis than these two species are from each other, in agreement with paleontological and morphological evidence. The evolutionary divergence of several classes of expressed DNA sequences was compared with that of total single-copy DNA. Between S. franciscanus and S. purpuratus the divergence of cDNA made from gastrula cytoplasmic poly(A)+ RNA is about half that of total single-copy DNA. Similar results were obtained for cDNA made from unfertilized egg poly(A)+ RNA. In contrast, sequences expressed in gastrula nuclear RNA have diverged almost as much as total single-copy DNA.

Animals↗

PubMed1985

Solutions to the problems of chronic disease management in rural settings.

Recent changes in disease patterns in the United States from acute to chronic disorders and the maldistribution of medical manpower have disproportionately affected rural residents. Programmatic attempts to alter the medical care system in rural areas have traditionally centered on increasing the number of primary providers. In central Mississippi, two innovative alternative models of chronic disease management have been evaluated. The disease focus was high blood pressure and the two management models emphasized: the use of local residents as health facilitators or health counselors, and the use of self-help groups in family and church settings. Eighteen months of outcome data indicated that the health facilitator model was controlling 80 percent of the hypertensives participating; the family-based self-help groups were controlling 90 percent; and, the church-based self-help groups were controlling 79.9 percent. These community-based models of chronic disease management have broad implications for other geographic areas and other chronic disorders.

Chronic Disease↗

PubMed1985

A new nuclear magnetic resonance property of lung.

Inflated lung has a nuclear magnetic resonance (NMR) free-induction decay (FID) which is short compared with that of collapsed lung and those of other body tissues. An almost identically short FID is obtained from a slurry of 5-micron alumina particles in water. Interfaces between air and water in lung and between alumina and water in the slurry appear to be the source of spatial internal magnetic inhomogeneities which produce NMR line broadening and the short FID. Paired images that included lung, taken with paired symmetric and asymmetric NMR spin-echo sequences, permit the generation of an image, by subtraction, of the lung isolated from surrounding tissue. These new lung images are neither proton density, T1 (spin-lattice relaxation time), nor T2 (spin-spin relaxation time) images. They complement current NMR images and provide information about regional lung inflation. This previously unrecognized NMR property of lung tissue has potential application in NMR imaging, in quantitative determination of lung water and its distribution, and in the quantitation of regional lung inflation.

Animals↗

PubMed1985

Urgent surgery for ventricular septal rupture complicating acute myocardial infarction.

Medical treatment of postinfarction ventricular septal rupture carries a high mortality. Delayed surgery can be done with good results but many patients die awaiting operation. In 1978 we decided that all such patients presenting to us should undergo urgent cardiac catheterization and surgery. Since then we have seen 22 such patients. Two decided against surgery and died in the hospital. Twenty agreed to surgery; in 15 of these an intra-aortic balloon pump was inserted before catheterization and in another four at the time of operation. Catheterization was performed without complication, and surgery was performed within 2 days of septal rupture in all 20 patients. Twelve patients (60%) survived hospitalization. Three patients died of pump failure shortly after surgery; five died after a second operation for free wall rupture (n = 2) or persistent or recurrent septal defect (n = 3). Two other patients survived reoperation. Survivors were significantly younger than nonsurvivors and had a higher cardiac index and a lower shunt ratio. At a mean follow-up of 47.9 months, there has been one late noncardiac death. Eleven patients survive, all in class I or II. We conclude that in patients with septal rupture urgent surgery results in improved near-term survival compared with known survival rates in medically treated patients. Early recurrent rupture is common and often disastrous and requires refinement in operative technique. Age, cardiac index, and shunt volume are related to surgical outcome. Hospital survivors do very well on a long-term basis. We recommend continuation of this aggressive approach.

Age Factors↗

PubMed1984

Skin metastases confined to a field of previous irradiation. Report of two cases and review of the literature.

Two cases of tumor recurrence within a previously irradiated skin area are reported. Typical lesions evolve from an erythematous base and progress to induration and tumor papules. A review of clinical literature indicates that irradiation does not increase the frequency of metastases. Experimental data suggest that irradiation does increase metastases as a result of both local mechanical factors and increased tumor-cell survival.

Adenocarcinoma↗

PubMed1984

Insertion of a short repetitive sequence (D88I) in a sea urchin gene: a typical interspersed repeat?

A comparison has been made between the Sp88 gene regions of the DNAs of the sea urchins Strongylocentrotus purpuratus (Sp.) and Strongylocentrotus drobachiensis (Sd.). Examination of the 3' terminal part of the transcribed region revealed a short repetitive sequence present in Sd. but absent from Sp. A 12-nucleotide sequence present once in Sp. is almost perfectly duplicated at both ends of the repeat in Sd., suggesting that a mobile repeat was inserted in the Sd. genome. Other members of this family of repeated sequences occur in many interspersed locations in the genomes of both species. Except for the insertion duplication, the inserted sequence lacks direct or reverse repeats.

Animals↗

PubMed1984

Determination of lung water content and distribution by nuclear magnetic resonance.

The present study was designed to determine the value of nuclear magnetic resonance (NMR) imaging as a technique for quantifying lung water distribution and to estimate the degree of spatial resolution achieved by this technique. The spatial distribution of water was determined in six small (0.76 ml) rat lung tissue specimens by an NMR line-scan technique. After NMR imaging, each lung specimen was frozen and subdivided into slices; the gravimetric lung water content for each lung slice was compared with the integrated NMR water content over the volume corresponding to the same lung slice. In each tissue specimen, NMR and gravimetric lung water values were significantly correlated; the correlation coefficient for the pooled data for all six lung specimens was 0.91 (P less than 0.01). In two lung specimens, NMR values tended to be slightly higher than the gravimetric values. The magnitude of the difference between NMR and gravimetric values was generally less than 20% and only occasionally exceeded 25%. Our results suggest that the NMR-imaging method provides satisfactory estimates of lung water content and its distribution; the resolving power of the technique is excellent, as shown by its ability to detect water content differences between lung tissue slices of volume as small as 0.076 ml.

Animals↗