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Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 541 records · Page 30Linked to original sources

4-N-acylfortimicins B and the preparation of fortimicin A from fortimicin B.

Selective 4-N-acylation of fortimicin B (2) has been accomplished by 4-N-acylation of 1,2',6'-tri-N-benzyloxycarbonylfortimicin B (4) followed by hydrogenolysis of the N-protecting benzyloxycarbonyl groups. In this manner, fortimicin B was converted into fortimicin A (1), and a series of 4-N-acylfortimicins B (3) was prepared for antibacterial assay. The key intermediate, 1,2',6'-tri-N-benzyloxycarbonylfortimicin B, was prepared either directly from fortimicin B or by converting fortimicin A into 1,2',6',2''-tetra-N-benzyloxycarbonylfortimicin A (6a), followed by selective hydrolysis of the 4-N-(N-benzyloxycarbonyl)glycyl group of the latter.

Acylation↗

Transcription and processing of a yeast tRNA gene containing a modified intervening sequence.

The tRNA(3) (Leu) gene from yeast contains an intervening sequence of 32 nucleotides not present in mature tRNA. This sequence is transcribed and subsequently removed during the maturation of the RNA. To probe the involvement of this region of the gene in transcription and processing of the pre-tRNA(3) (Leu), the yeast DNA was cloned in plasmid pBR322 and a 21-base-pair DNA fragment corresponding to the lac operator was inserted into the intervening sequence. Insertion was done at a cleavage site for the restriction endonuclease Hpa I that occurs 19/20 base pairs from the 5' end of the intervening sequence. The parent and modified plasmids were then transcribed in a Xenopus germinal vesicle extract. RNA-fingerprint analysis of the transcription products revealed that both the tRNA(3) (Leu) gene and its modified counterpart were accurately transcribed. Transcription products corresponding to mature tRNA(3) (Leu) and pre-RNA(3) (Leu) with the normal and lac-containing intervening sequence were identified. Precursors extended at their 5' and 3' ends were also present. Both parent and modified genes were transcribed efficiently, and the various products accumulated in similar amounts, indicating that no deleterious effects on transcriptional competence, stability of the transcripts, or processing result from insertion of the 21-base-pair lac operator DNA. Incubation of pre-tRNA molecules that contained intervening sequences but were 5' and 3' mature with a yeast ribosomal wash fraction resulted in excision of the intervening sequence and, in the presence of ATP, ligation of the resulting half-tRNA molecules. The presence of RNA complementary to lac operator DNA neither inhibited the excision and splicing activities nor altered the site of the junction.

Base Sequence↗

The relative weightings of visual and nonvisual coding in a simple motor learning task.

A linear positioning task was used to examine the effects of visual and nonvisual inputs on motor learning. The experiment had three factors with two levels of each namely: sensory modality (visual-nonvisual), transfer at recall (changed-unchanged), size of movement (25.4 cm, 50.8 com). Three dependent variable were used: absolute error (AE), constant error (CE), and variable error (VE). The results suggest that visual dominance causes disruption of recall in the visual, changed conditions. No disruption of recall was found for the nonvisual condition other than in terms of CE with respect to movement sizes. The results are taken to follow Posner et al.'s (1976) theory of visual dominance, but some account of the spatial qualities of visual and kinesthetic information is needed.

Journal Article↗

Isolation and evaluation of clostridia from clinical sources.

During a two-year period, 133 isolates of clostridia from clinical courses were obtained. These isolates are reviewed as to clinical significance and antimicrobial susceptibility. Adequate charts were available on 63 patients, nine (14%) of whom had their clinical source significantly altered by the presence of clostridia. Clostridia of little or no clinical significance were isolated from blood cultures from six patients. The occurrence of clostridial infections is unpredictable, and adequate clinical information is necessary to determine the need for identification of clostridial isolates.

Clostridium↗

Fetal breathing.

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Animals↗

Synthesis of 3-O-demethylfortimicins.

Treatment of fortimicin B with lithium in ethylamine gave 3-O-demethylfortimicin B. The latter was converted by methodology developed with fortimicin B to 3-O-demethylfortimicin A, 4-N-sarcosyl-3-O-demethylfortimicin B, 4-N-beta-alanyl-3-O-demethylfortimicin B, and 4-N-(beta-aminoethyl)-3-O-demethylfortimicin B. 3-O-demethylfortimicin A and the 4-N-acyl-3-O-demethylfortimicins B had appreciably higher antibacterial activities than the corresponding parent fortimicins. Most significant was the increased activity of 3-O-demethylfortimicin A relative to fortimicin A against a variety of strains of Pseudomonas aeruginosa.

Aminoglycosides↗

Studies in normal pregnancy. III. Fatty acid composition of serum phosphoglycerides and cholesterol esters.

Metabolic and hormonal influences on liver lipid synthesis are reflected in the relative fatty acid composition of serum lecithin. Thus, a successive decrease in essential fatty acids (EFA), i.e. n-6 fatty acids, during pregnancy would indicate an incipient EFA deficiency at the time of delivery. Furthermore, reciprocal changes in linoleic and arachidonic acids during the 1st trimester with an increase in arachidonic acid would suggest an enhancement of the Greenbeg Pathway (Pathway II) in lecithin synthesis presumably caused by estrogen influence. During the 2nd and 3rd trimester, reciprocal changes in lecithin content of palmitic and stearic acids are similar to changes appearing under cholestasis. It is furthermore suggested that variations in the utilization of linoleic acid in cholesterol esters (expressed as cholesterol ester 18:2/lecithin 18:2) might reflect changes in plasma cholesterol esterification by the enzyme lecithin-cholesterol-acyl-transferase (LCAT). Then, in late pregnancy, in relation to a subclinical cholestatic liver engagement, LCAT activity would increase as judged from this ratio as well as the increased linoleic acid in cholesterol esters.

Adolescent↗

synthesis of 2-deoxyfortimicins and 1-deamino-2-deoxy-2-epi-aminofortimicins via 2-O-methanesulfonylfortimicin B.

The synthesis of 2-deoxyfortimicins A (15) and B (11) and 1-deamino-2-deoxy-2-epi-amino-fortimicins A (18) and B (12) is described. Two routes have been developed for synthesis of the key intermediate 2-O-methanesulfonylfortimicin B (7). One route involves selective blocking of fortimicin B with B-benzyloxycarbonyl groups followed by formation of a 4,5-salicylaldehyde oxazolidine derivative. Subsequent mesylation followed by deblocking gave 7. A more efficient route to 7 involves concomitant salicylaldehyde Schiff base and 4,5-oxazolidine formation followed by mesylation and hydrolysis. The formation of 1,2(R)-epiminofortimicin B (8) from 7 followed by RANEY nickel reduction gave 2-deoxyfortimicin B and 1-deamino-2-deoxy-2-epi-aminofortimicin B, which were converted to the corresponding fortimicin A derivative by selective N-blocking, N-acylation and subsequent deblocking. The antibacterial activities of the new fortimicin A derivatives are presented.

Aminoglycosides↗

A minimal injury restraining device for swine.

A device consisting of a sling and hoist was developed to restrain bleeder swine. The design enabled repeated restraint of animals without causing injury to the animals or operator. The restrainer was inexpensive, mobile and adaptable to small or large animals.

Animals↗

Non-operative arterial embolisation in primary liver tumours.

Three patients with primary hepatic tumours were treated by selective arterial embolisation with gelatin-foam fragments to induce necrosis. In the two with histologically proved hepatocellular carcinoma ultrasonography suggested that necrosis had been induced, as did the rapid initial falls in serum alpha-fetoprotein concentration by 95 and 81% of the original values respectively. Treatment was continued with a course of adriamycin, and both patients remained well and symptom free at 10 and 12 months. In the third patient, who had an expanding and highly vascular benign hepatic adenoma associated with use of a contraceptive pill, embolisation obliterated the tumour mass. Tumour embolisation should be regarded as only the first step in managing hepatocellular carcinoma and as a means of reducing appreciably the viable tumour mass before chemotherapy. It may be used as the primary and definitive treatment in patients with benign liver tumours.

Adenoma↗

Protein-protein interactions of proteolytic fragments of actin.

Proteolytic fragments of actin, prepared by removal of up to sixty-eight residues from the N-terminal end of the molecule, can form filamentous structures after denaturation in urea solution. The filaments have a diameter similar to F-actin filaments and interact with myosin and tropomyosin. A fragment comprising residues 1 to 207 of the actin sequence did not form filaments or interact with myosin after the urea treatment.

Actins↗

Regional distribution of amino acids in Friedreich's ataxia brains.

The distribution of amino acids in two Friedreich's ataxia brains is compared to 4 control brains. Glutamate and GABA were decreased in the cerebellar hemispheres and/or in the vermis. Taurine concentrations were uniformly elevated throughout the areas studied. Taurine/glutamate and taurine/GABA ratios were consistently elevated in Friedreich's ataxia brains, whereas glutamate/glutamine ratios were consistently decreased (with normal glutamine concentrations).

Amino Acids↗

Changes in serum creatine kinase isoenzyme activities after surgical procedures and cardioversion.

Serum activities of creatine kinase (CK) and its isoenzymes were monitored before and 16 to 20 hours after a variety of surgical procedures and cardioversion. Changes in total CK and CK MM activities in the surgical patients were consistent with the extent of trauma; changes in these activities in the cardioversion patients were more variable, ranging from -2 to 1829 U/l, and were unrelated to the applied electrical force. CK MB activity was unchanged after cystoscopy but rose moderately in 60% of patients after cholecystectomy, in 43% of patients requiring only implantation of a new pacemaker box, and in 87% of patients after implantation of an entire pacemaker system. No increase exceeded 6U/l. Fifty per cent of patients requiring cardioversion showed rises; the maximum value was 40.9 U/l.

Adult↗

4-N-Aminoacylfortimicins E.

The conversion of fortimicin E, a minor metabolite from the Micromonospora olivoasterospora fermentation which also produces fortimicin A and fortimicin B, to four 4-N-aminoacylfortimicins E was accomplished. The new 4-N-aminoacylfortimicins E showed only weak antimicrobial activity against several Gram-negative and Gram-positive microorganisms.

Aminoglycosides↗