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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 685 records · Page 38Linked to original sources

Genetic variation in the M antigen of group A streptococci: reassortment of type-specific markers and possible antigenic drift.

The phylogenetic relationships of 73 strains of group A Streptococcus isolated over a six-year period from a population with a high prevalence of streptococcal infections were analyzed with use of four serotype-specific markers: the serum opacity factor (OF), the T antigen, the determinant of the M antigen that precipitates with antibody, and the M antiphagocytic determinant. OF inhibition tests divided the strains into five subtypes: a, b, c, d, and e. Strains within subtypes a, b, and c shared a previously unidentified M precipitin. The identification of this new common M precipitin was based on absorption studies, double agar immunodiffusion, and immunoelectrophoresis analysis. Antisera directed against representative strains from subtypes a, b, and c contained cross-reactive bactericidal antibody, and absorption studies indicated that determinants of the M precipitins were identical, whereas determinants of resistance to phagocytosis were closely related but not identical. The association of a common M precipitin with three different OF antigens, two different T antigens, and three different, yet similar, antiphagocytic determinants is discussed in light of the possibility that the genes that code for these antigens have reassorted or recombined. Moreover, the possibility that differences in the antiphagocytic determinants of these strains have resulted from antigenic drift in a common gene is considered.

Absorption↗

Estimation of gestational and skeletal age in Macaca mulatta.

Results of qualitative and quantitative studies of prenatal skeletal development in Macaca mulatta are presented. Longitudinal radiographic observations were carried out on 20 monkeys of known gestational age, beginning on 120 days of gestation until the neonatal stage of skeletal development. These studies were based on multiple uterotomies on each pregnant female. The technique described provides accurate data on prenatal bone ossification, and permits an accurate estimation of fetal age in pregnant rhesus monkeys with unknown conception dates.

Age Determination by Skeleton↗

Structural evidence for methionine at the reactive site of human alpha-1-proteinase inhibitor.

An unadecapeptide, obtained by papain digestion of denatured human alpha-1-proteinase inhibitor (alpha-1-PI), has been isolated and sequenced. The structure of this fragment overlaps with the NH2-terminal sequence of modified inhibitor (alpha-1-PI) prepared from dissociated complexes of alpha-1-PI with trypsin, chymotrypsin, and elastase. Furthermore, structural homology with the reactive centers of proteinase inhibitors from other sources is readily detectable. Methionine has been found to occupy the apparent P1 position in alpha-1-PI and the potential inactivation of the inhibitor by oxidation of this critical residue may be important in obtaining a biochemical link with the development of lung disease.

Amino Acid Sequence↗

Transformation of marmoset lymphocytes in vitro with Herpesvirus ateles.

Circulating lymphocytes from three species of marmoset monkeys were transformed in vitro with Herpesvirus ateles (HVA) either by co-cultivation with lethally X-irradiated HVA-producing lymphoblastoid cells or by infection with cell-free virus: 42 transformed lymphocyte cultures were obtained from 72 transformation attempts. Attempts to transform squirrel monkey lymphocytes were unsuccessful in 29 attempts. Association of HVA with each transformed culture was demonstrated by staining of antigen-positive cells in indirect fluorescent antibody (FA) tests and recovery of HVA after co-cultivation of the transformed cells with permissive monolayer cells. Cells of most transformed cultures possessed T lymphocyte properties: i.e. formation of E rosettes, reactivity with a specific anti-marmoset T lymphocyte serum and lack of surface Ig.

Animals↗

Unique structures formed by pyrimidine-purine DNAs which may be four-stranded.

Pyrimidine-purine DNAs with repeating sequences can be made to undergo a reversible transition to possibly a tetra-stranded complex. Physicochemical characterization of the new structures and model building are consistent with, in the case of d(TC)n-d(GA)n, a tetra-stranded complex forming by the addition of d(GA)n to the remaining space in the major groove of the triple-stranded complex d(TC)n-d(GA)n-d(CT)n. A possible role for tetra-stranded complexes in chromosome condensation is suggested by the natural occurrence of repeating sequence pyrimidine-purine DNAs and the properties of condensed chromosomes.

Base Sequence↗

Inactivation of human alpha 1-proteinase inhibitor by thiol proteinases.

Human plasma alpha1 proteinase inhibitor is the body's principal modulator of serine proteinases (such as those released from phagocytic cells). Cysteine-active-site proteinases, which are not inhibited, have now been found to inactivate this important inhibitor by proteolytic cleavage of a scissile peptide bond. Papain carries out this inactivation catalytically, whereas cathepsin B1 acts stoicheiometrically. Thus thiol proteinases could easily disrupt the delicately regulated balance between serine proteinases and alpha1 proteinase inhibitor.

Cathepsins↗

Treatment of rhabdomyosarcoma in children with surgery, radiotherapy and chemotherapy.

From May, 1970 through December, 1972, Children's Cancer Study Group entered 112 patients on an amended treatment program for rhabdomyosarcoma and undifferentiated sarcoma in children. These patients had Group II disease with residual tumor remaining after surgery, or metastatic disease at onset. Another group consisted of patients who previously had treatment with surgery and radiotherapy and had recurrent disease. Cyclophosphamide was added to a previously used drug regimen which consisted of actinomycin D and vincristine. The drugs were given sequentially in repeated cycles for 18 months. Of 97 evaluable patients, there were 24 with microscopic residual disease, 37 with gross residual disease, 22 with metastatic disease at onset, and 14 patients who were treated with chemotherapy for the first time with recurrent or metastatic disease. All patients have been followed for 3 or more years. Survival in each group was 70.8%, 43.2%, 27.2%, and 28.2%, respectively. Although the number of complete remissions was greater than with two-drug therapy, survival with three-drug therapy was not significantly different than that seen in the earlier study.

Adolescent↗

Antiviral activity of some beta-diketones. 1. Aryl alkyl diketones. In vitro activity against both RNA and DNA viruses.

The discovery that 4-[3-ethyl-6-[(3,4-methylenedioxy)phenyl]-3-hexenyl]-3,5-heptanedione (40) exhibited an in vitro inhibitory effect against equine rhinovirus led to a structure--activity study to establish the criteria for optimum activity. Modification of the bridge included removal of the ethyl group and reduction of the double bond. The heptanedione was replaced with hexanedione and pentanedione with a minimal effect. The effect of replacing the heptanedione with beta-keto esters and monoketones was also investigated. Maintaining the hexamethylene bridge and heptanedione, the methylenedioxy group was replaced with various substitutents. In general, most substituents did not adversely affect activity particularly against equine rhinovirus although there was some variation in activity against herpesvirus. Strongly hydrophilic groups significantly reduced activity. Finally, the effect of varying the length of the alkyl bridge was examined in the 4-hydroxyphenyl series, where peak activity was attained with n = 8.

Antiviral Agents↗

Bacteria in neonatal omphalitis.

A 6-year study of bacteria isolated from swabs taken from clinically apparent infections of the stump of the umbilical cord showed an overall infection rate of 0.7% (200/27,107), with a preponderance of Gram-negative organisms as compared with Gram-positive organisms (171/118), an excess which was statistically significant. When the data were broken down into premature and non-premature nurseries, the incidence of infection in the former was 2.08% (84/4028) and in the later 0.5% (116/23,079), a highly significant statistical difference. Most of the organisms isolated from the premature nurseries were Gram negative (83/120) and this finding too was statistically highly significant.

Bacteria↗

Hydroxylation of 5,5-diphenylhydantoin (phenytoin) by dog liver microsomes.

Chang and Glazko in 1972 had reported failure to demonstrate any production from 5-5-diphenylhydantoin (phenytoin, DPH) by dog liver microsomes of either 5-(m-hydroxyphenyl-5-phenylhydantoin (m-HPPH) or 5-(P-hydroxyphenyl-5-phenylhydantoin (p-HPPH), metabolites of DPH produced by the dog in vivo. We have incubated DPH with 9,000 X g supermatants of dog liver homogenates and with suspensions of separated microsomes with added NADPH generating system, Mg(2+), and nicotinamide and have demonstrated the production of both m-HPPH and p-HPPH. Both metabolities were detected by thin-layer chromatography of extracts of the incubation mixtures. Detection and roughly quantitative measurement of m-HPPH were also accomplished with gas chromatography.

Animals↗