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Biomedical subjects

J King

Publications and source records attributed to J King.

At least 325 records · Page 18Linked to original sources
PubMed1985

Assembly-controlled autogenous modulation of bacteriophage P22 scaffolding protein gene expression.

In the assembly of bacteriophage P22, precursor particles containing two major proteins, the gene 5 coat protein and the gene 8 scaffolding protein, package the DNA molecule. During the encapsidation reaction all of the scaffolding protein molecules are released intact and subsequently participate in further rounds of DNA encapsidation. We have previously shown that even though it lies in the center of the late region of the genetic map, the scaffolding protein gene is not always expressed coordinately with the remainder of the late proteins and that some feature of the phage assembly process affects its expression. We present here in vivo experiments which show that there is an inverse correlation between the amount of unassembled scaffolding protein and the rate of scaffolding protein synthesis and that long amber fragments of the scaffolding protein can turn down the synthesis of intact scaffolding protein in trans. These results support a model for scaffolding protein regulation in which the feature of the assembly process which modulates the rate of scaffolding protein synthesis is the amount of unassembled scaffolding protein itself.

Capsid↗
PubMed1985

Cortisone fails to affect levels of islet cell surface antibodies and incidence of diabetes in the BB rat.

Cortisone acetate (250 micrograms/kg X day) was given by im injections to 40 21-day-old diabetes-prone BB rats. The animals were followed longitudinally to determine islet cell surface antibodies (ICSA), as an expression of an abnormal immune reaction against the pancreatic islet cells and plasma glucose to estimate the degree of metabolic control. ICSA were detected 10-150 days before the diagnosis of diabetes. In the cortisone-treated group the diabetic rats showed significantly higher ICSA values compared to the nondiabetic ones, both in frequency of positive tests (P less than 0.05) and in mean binding values (P less than 0.02). In the control group, no difference in ICSA levels were seen between diabetic and nondiabetic rats. The cortisone regimen also failed to influence the degree of insulitis, commonly associated with diabetes in these rats. These experiments in well defined animals which spontaneously develop diabetes do not support the use of low dose cortisone treatment in attempts to improve or prevent insulin-dependent diabetes in human subjects.

Animals↗
PubMed1984

DNA injection proteins are targets of acridine-sensitized photoinactivation of bacteriophage P22.

Viruses and other nucleoprotein complexes are inactivated on exposure to white light in the presence of acridine and related dyes. The mechanism is thought to involve generation of singlet oxygen or related species, but the actual molecular targets of the inactivating event have not been well defined. We have re-examined the mechanism of dye-sensitized photoinactivation taking advantage of the well characterized bacteriophage P22. Though the inactivated phage absorb to their host cells, the cells are not killed and genetic markers cannot be rescued from the inactivated phage. These observations indicate that the chromosome is not injected into the host cell. However, the DNA of the damaged particles shows no evidence of double-stranded breaks or crosslinking. The DNA injection process of P22 requires three particle-associated proteins, the products of genes 7, 16 and 20. Gp16, which can act in trans during injection, is inactivated in the killed particles. Sodium dodecyl sulfate/polyacrylamide gel analysis reveals that gp16, gp7 and gp20 are progressively covalently damaged during photoinactivation. However, this damage does not occur in particles lacking DNA, indicating that it is DNA-mediated. Similar findings were obtained with acridine orange, acridine yellow, proflavin and acriflavin. These results indicate that the actual targets for inactivation are the DNA injection proteins, and that the lethal events represent absorption of photons by acridine molecules stacked in a region of DNA closely associated with the injection proteins.

Acridines↗
PubMed1984

Characterization of liposomes prepared using a microemulsifier.

A new type of device can prepare liposomes continuously, in large quantities and with excellent aqueous space capture efficiency. At initial lipid concentration of 300 mumol/ml these liposomes capture approx. 75% of cytosine arabinoside used as an aqueous space marker. Liposome size can be reduced by increasing the number of times the preparations are recycled through the microemulsifier. Liposomes less than 0.1 micron in diameter, as shown by electron microscopy, can be made easily. Liposomes prepared at 300 mumol/ml, composed of phosphatidylglycerol/phosphatidylcholine/cholesterol in a 0.1:0.4:0.5 molar ratio leaked less than 1% of entrapped cytosine arabinoside (Ara-C) at 4 degrees C, and less than 10% Ara-C at 37 degrees C plus serum, over a 48 h period. These liposomes could be useful for a number of applications including diagnostics, therapeutics and model membrane studies.

Biochemistry↗
PubMed1984

Steps in the stabilization of newly packaged DNA during phage P22 morphogenesis.

The protein products of three adjacent P22 genes, 4, 10 and 26, are required for the stabilization of DNA newly packaged into P22 phage capsids. We have isolated unstable DNA containing capsids from cells infected with mutants defective in these genes. All three classes could be converted into mature phage in vitro, confirming that they represent intermediates in particle maturation. The first of the three proteins to add to the newly filled capsids is gp4, followed by gp10 and gp26. The active form of gp4 sediments at 3 S, while the active forms of both gp10 and gp26 sediment at 5 S. These soluble subunits appear to polymerize onto the newly filled capsids to form the neck of the mature phage, the channel for DNA injection. Since gp4 is the first protein to act after DNA packaging, the unstable DNA containing capsids from 4- -infected cells must represent the direct product of the packaging of DNA into procapsids. The major fraction of these capsids lost activity with a half-life of 1.1 minutes at 23 degrees C, though they were much more stable at 0 degree C. Electron microscopic observations indicated that the loss of activity was due to the DNA exiting from the incomplete capsids. The marginal stability of the condensed DNA molecules within capsids is consistent with models of ATP-driven condensation and spontaneous DNA ejection. The basis of the stability of these highly condensed molecules remains to be determined.

Capsid↗
PubMed1984

Computed tomography of rhinocerebral mucormycosis.

Rhinocerebral mucormycosis is a rare fungal infection which is frequently fatal. Survival depends on early diagnosis and immediate aggressive treatment. Previously described radiological changes have been non-specific. The CT features of two cases are described. Non-enhancement of the superior ophthalmic vein and ophthalmic artery appears to be a CT sign specific to this disease.

Adolescent↗
PubMed1984

Phospholipids in tracheal effluent from infants with severe respiratory distress syndrome.

The physiologic aberration that causes abnormal alveolar surface tension in the lungs of infants with RDS was investigated by measuring relative quantities of surfactant-related phospholipids in tracheal effluent from infants with RDS. A preliminary study in premature lambs demonstrated that the percent DSPC (molar ratio of DSPC to total phospholipid) is similar in tracheal effluent and lung lavagate. The percent DSPC in tracheal effluent from human infants with RDS was similar to the percent DSPC in effluent from non-RDS infants on the first day of life (47.4% +/- 2.9 vs 46.7% +/- 1.2), and remained constant during the first 8 days of life. Phosphatidylglycerol (PG) was universally absent in effluent from RDS infants on the first and second day of life but appeared by the eighth day of life in all infants who remained intubated. PG was present in tracheal effluent from only 10 of 16 non-RDS infants on the first day of life. These findings suggest that, in regard to the surface-active lecithin content, surfactant from RDS infants is qualitatively normal and that the absence of RDS is not dependent on the presence of PG.

Animals↗
PubMed1984

Single amino acid substitutions influencing the folding pathway of the phage P22 tail spike endorhamnosidase.

Temperature-sensitive mutations in the gene for the thermostable tail spike of phage P22 interyFere with the folding and subunit association pathway at the restrictive temperature but not with the activity or stability of the protein once matured. The local sites of these mutations and the mutant amino acid substitutions have been determined by DNA sequencing. Of 11 temperature-sensitive folding mutations, 3 were replacements of glycine residues by polar residues, and three were replacements of threonine residues by residues unable to form a side-chain H-bond. There were no proline replacements. Two of the temperature-sensitive sites in which threonine residues were replaced by isoleucine residues were homologous. These sequences probably maintain the correct local folding pathway at higher temperatures. The temperature-sensitive amino acid substitutions appear to destabilize a thermolabile intermediate in the wild-type folding pathway or to increase the rate of a competing off-pathway reaction.

Amino Acid Sequence↗
PubMed1984

Family data on sixteen chromosome 1 loci.

Lod scores are presented from the published and unpublished data of the Galton Laboratory, and from published data on sixteen chromosome 1 loci, AMY, AT3, CAE, CMT1, EL1, ENO1, FUCA, Fy, GDH, PEPC, PGD, PGM1, Rh, Sc, UMPK and 1qh.

Chromosome Mapping↗
PubMed1984

A revised map of chromosome 1.

The genetic map of chromosome 1 reported by Keats, Morton & Rao (1981) has been updated using recent recombination data and regional assignments from the Galton Laboratory (King, 1982a) and from the current literature. A maximum likelihood mapping technique using pairwise recombination data without a chiasma map was developed, based on the principles of Rao et al. (1979) and Keats et al. (1981). The development of this new method was found to be necessary when inconsistencies were encountered using a method which combines recombination data and physical data through the chiasma map. These inconsistencies could be due to appreciable chiasma movement, incorrect physical assignments or technical and biological variation in lod scores.

Chromosome Mapping↗
PubMed1984

Mutagenic impurities in 1,3-dichloropropene preparations.

A widely used pesticide, 1,3-dichloropropene [(DCP) CAS: 542-75-6], has been reported to be mutagenic to Salmonella typhimurium TA100, but large variations in specific mutagenic activity have been observed among different preparations. The purposes of this investigation were to determine the probable cause of the interpreparational variation and to provide new information on the nature of the mutagenic activity. Four preparations were assayed for mutagenic activity before and after silicic acid chromatography. None of the preparations retained mutagenic activity after chromatography, but each contained direct-acting mutagenic polar impurities. The specific mutagenic activities of the unpurified DCP samples appeared to be determined by the mutagenic activities of their polar impurities. A mixture of mutagenic polar impurities could be regenerated by refluxing a purified DCP preparation for 6 hours. The fraction of polar impurities from one of the preparations was analyzed by gas chromatography-mass spectroscopy. Although its composition was too complex to characterize completely, two known mutagens, epichlorhydrin (CAS: 106-89-8; 1-chloro-2,3-epoxypropane) and 1,3-dichloro-2-propanol (CAS: 96-23-1), were tentatively identified. In view of these results, future studies are required to establish whether DCP itself is a chemical carcinogen or whether its previously observed carcinogenicity resulted from the presence of mutagenic impurities.

Allyl Compounds↗
PubMed1983

Further experience with long-term captopril therapy in severe refractory congestive heart failure.

Fifty patients in severe congestive heart failure (CHF) were treated with captopril (Capoten; Squibb), an oral angiotensin-converting enzyme inhibitor, over a 2-year period (range 3-24 months, mean 8,6 +/- 7,7 months). At entry, all patients were in New York Heart Association (NYHA) functional class IV despite high-dose diuretic and conventional vasodilator therapy. The overall cumulative survival at 6 and 12 months was 64% and 53% respectively. There were 22 deaths (18 during captopril therapy) including 8 sudden deaths. At 2-year follow-up (mean 14,6 +/- 6,9 months), there were 25 survivors on captopril; 18 in NYHA class I or IIS and 7 in class IIM or III. Diuretic requirements were decreased considerably in all. Side-effects were common but transient and in no case did captopril have to be withdrawn. We confirm our earlier conclusion that captopril has long-term beneficial effects and is a highly effective drug in the treatment of patients with CHF refractory to currently accepted therapy. Sudden death despite satisfactory clinical improvement continues to cause concern. Precautions which may reduce or avoid these are briefly discussed.

Adolescent↗
PubMed1983

Delayed onset of overt porphyria cutanea tarda in a patient on long-term haemodialysis. A case report.

After 7 years on haemodialysis, a 37-year-old anephric man developed cutaneous lesions of the hands, arms and face, shown by skin biopsy to be compatible with porphyria cutanea tarda (PCT) (symptomatic porphyria). Elevated levels of plasma uroporphyrin and 7-COOH porphyrin were detected alongside a predominant isocoproporphyrin fraction in the faeces by means of quantitative thin-layer chromatography, confirming the diagnosis of overt PCT. The plasma uroporphyrin did not pass into the dialysate, even after chloroquine therapy. There was no evidence of hereditary PCT, chronic liver disease or iron overload, although the patient had a history of excessive alcohol consumption. The overt PCT developed after 8 months of home dialysis using softened water with high aluminium concentrations and subsided clinically and biochemically when the softened water was replaced by deionized water.

Adult↗
PubMed1983

Treatment of caroticocavernous fistulae with detachable balloons introduced by percutaneous catheterization.

Five patients with caroticocavernous fistula were treated by new, interventional angiographic techniques. In four patients, latex balloons filled with a silicone polymer were introduced into the cavernous sinus via the transfemoral route and detached; this resulted in complete obliteration of the caroticocavernous fistula and preservation of the internal carotid artery flow in two of the four patients. In the fifth patient, stainless steel coils were introduced into the cavernous sinus via the superior ophthalmic vein which had previously been surgically exposed. These percutaneous, angiographic techniques of intervention should be considered the initial treatment of choice for caroticocavernous fistulae.

Adolescent↗