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Biomedical subjects

S Josephson

Publications and source records attributed to S Josephson.

At least 73 records · Page 4Linked to original sources

Synthesis of mixed oligodeoxyribonucleotides following the solid phase method.

A method for the synthesis of mixed dimers, trimers and oligonucleotides on a solid support using monomeric protected nucleoside phosphochloridites (1a-d) has been developed and the different nucleoside reagents, and the results show that yields of different oligomers in a mixture could be directly correlated to the concentration of the four reagents. Separation of mixed oligomers on a reversed phase C18 column has also been studied.

Chromatography, High Pressure Liquid↗

Leader arrangement in the adenovirus fiber mRNA.

Four oligonucleotides, complementary to the adenovirus 2 (ad2) fiber mRNA were chemically synthesized and used as primers to study the 5' end of that messenger. The oligonucleotides which were 8, 10, 12, and 14 nucleotides long had a common 3'-terminal sequence, TAC, complementary to the initiating codon of the fiber mRNA. The 5'-32P-labeled oligonucleotides were hybridized to polyadenylated mRNA from ad2-infected cells and the primer was extended, using reverse transcriptase. When the resulting products were analyzed by polyacrylamide gel electrophoresis multiple distinct bands could be identified by autoradiography. The extension products were characterized by hybridization and sequence analysis. The most prominent band contained the well-known tripartite lead which is attached to many different late adenovirus mRNAs. In addition, four differently spliced leaders were characterized which, besides the three segments of the tripartite leader, contain one or two auxilliary segments. A kinetic analysis of the different leaders during lytic adenovirus infection shows no temporal variation.

Adenoviridae↗

Experimental obstructive hydronephrosis in newborn rats. II. Long-term effects on renal blood flow distribution.

Partial obstruction of one ureter was created in newborn rats. The weights and blood flows (using the 86Rb-extraction method) of the cortex and outer and inner medulla were examined nine weeks later, i.e., in the adult. The obstructed pelvis was found to be enlarged 7-fold. The whole kidney blood flow on the hydronephrotic side was reduced by 10%; this was compensated by an increase on the contralateral side. There was a tendency to redistribution of flow from the cortex to the outer medulla; no other effects on regional flow were observed. The weight of the hydronephrotic kidneys was the same as that of the kidneys in control rats; hence no apparent atrophy was present. In contrast, the contralateral intact kidney was hypertrophied. The weight distribution of the different regions remained unaltered. Thus, the inner medullary weight was unaffected also on the obstructed side, although it showed considerable deformation. In the discussion, it is proposed that atrophy of the hydronephrotic kidney was probably present, but it was not detected because of the biological variation and the small number of observations. This presumed atrophy was uniform in all the regions and parallel with the reduction of whole kidney blood flow; hence the regional flows were relatively unaffected. It is concluded that unilateral partial obstruction in the newborn rat causes (i) discrete, parallel reductions of hydronephrotic kidney weight and flow, which are (ii) unrelated to the size of the obstructed pelvis and (iii) completely compensated by increases in the contralateral intact kidney.

Animals↗

Renal function in dogs with chronic moderate unilateral ureteral obstruction.

Partial obstruction of the left ureter was created in seven dogs. Renal function was studied 3 weeks later. Total renal blood flow (RBF) and intrarenal blood flow distribution were studied using the microsphere technique. Glomerular filtration rate (GFR), effective renal plasma flow (CPAH) and the excretion of sodium and osmolar substances were determined using the clearance technique. RBF, GFR and CPAH in the hydronephrotic kidney were reduced to approximately 30% of the same parameters in the contralateral kidney. Urinary sodium excretion was consistently lower in the hydronephrotic than in the contralateral kidney. Volume expansion with isotonic saline solution revealed that this reduction of sodium excretion from the hydronephrotic kidney was out of proportion to the extent of GFR reduction. The contralateral unobstructed kidney did not compensate for this salt retention by increasing its sodium excretion.

Animals↗

Functional analysis of influenza RNA polymerase activity by the use of caps, oligonucleotides and polynucleotides.

The effects of caps, dinucleotides, oligonucleotides and polynucleotides on influenza virus RNA polymerase activity have been investigated. The results show that both methyl groups in a cap are necessary for optimal stimulation of polymerase activity. Both m7G(5')ppp(5')Am and ApG stimulated the influenza RNA polymerase activity and seemed to interact at different sites. Out of the 16 homopolynucleotides tested, seven inhibited influenza RNA polymerase by 50% at 2-10 micrograms/ml. Poly(G) gave a 90% reduction of influenza virus plaque formation at 10 micrograms/ml. An oligodeoxyribonucleotide complementary to the 12 terminal nucleotides of the 3' end of influenza virus RNA was synthesized. This oligonucleotide did not selectively inhibit influenza RNA polymerase.

DNA-Directed RNA Polymerases↗

Artificial carbohydrate antigens: the synthesis of a tetrasaccharide hapten, a Shigella flexneri O-antigen repeating unit.

The 8-methoxycarbonyloctyl glycoside of the tetrasaccharide hapten, O-alpha-L-rhamnopyranosyl-(1 leads to 2)-O-alpha-L-rhamnopyranosyl-(1 leads to 3)-O-alpha-L-rhamnopyranosyl-(1 leads to 3)-2-acetamido-2-deoxy-beta-D-glucopyranoside and the trisaccharide glycoside 8-methoxycarbonyloctyl O-alpha-L-rhamnopyranosyl-(1 leads to 3)-O-alpha-L-rhamnopyranosyl-(1 leads to 3)-2-acetamido-2-deoxy-beta-D-glucopyranoside were synthesized by sequential Koenigs-Knorr reactions from monosaccharide units. The tetrasaccharide represents the complete skeletal repeating unit of Shigella flexneri serogroup Y lipopolysaccharide. Both oligosaccharide haptens are functionalized for covalent attachment to proteins, cell surfaces, and solid supports. 1H-N.m.r. evidence for the conformations of these oligosaccharides in solution is presented and shown to be consistent with predictions based on the exo-anomeric effect.

Acetylglucosamine↗

Experimental obstructive hydronephrosis in newborn rats. I. Surgical technique and long-term morphologic effects.

Partial obstruction of one ureter was created in newborn rats and its effects were studied in the adult rat. The obstructed renal pelvis was found to be enlarged 10x. The parenchymal weight of this kidney was reduced by 8 per cent, primarily because of destruction of the papilla, and was completely compensated for by hypertrophy of the contralateral kidney. A high correlation was found between true volumes and areas on urography. The turnover time for urine in the hydronephrotic pelvis ranged from 47 to 473 min. The implications of this measurement for clearance values are discussed.

Animals↗