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Biomedical subjects

M Hayden

Publications and source records attributed to M Hayden.

At least 55 records · Page 3Linked to original sources

Analysis in vivo of the bacteriophage P22 headful nuclease.

Bacteriophage P22 packages its double-stranded DNA chromosomes from concatemeric replicating DNA in a processive, sequential fashion. According to this model, during the initial packaging event in such a series the packaging apparatus recognizes a nucleotide sequence, called pac, on the DNA, and then condenses DNA within the coat protein shell unidirectionally (rightward) from that point. DNA ends are generated near the pac site before or during the condensation reaction. The right end of the mature chromosome is created by a cut made in the DNA by the "headful nuclease" after a complete chromosome is condensed within the phage head. Subsequent packaging events on that concatemeric DNA begin at the end generated by the headful cut of the previous event and proceed in the same direction as the previous event. We report here accurate measurements of the P22 chromosome length (43,400( +/- 750) base-pairs, where the uncertainty is the range in observed lengths), genome length (41,830( +/- 315) base-pairs, where the uncertainty represents the accuracy with which the length is known), the terminal redundancy (1600( +/- 750) base-pairs or 3.8( +/- 1.8)%, where the uncertainty is the observed range) and the imprecision in the headful measuring device ( +/- 750 base-pairs or +/- 1.7%). In addition, we present evidence for a weak nucleotide sequence specificity in the headful nuclease. These findings lend further support to, and extend our understanding of, the sequential series model of P22 DNA packaging.

DNA, Viral↗

Prenatal diagnosis of asplenia/polysplenia syndrome.

Complex congenital heart disease with atrioventricular block was detected prenatally in two fetuses at 34 and 28 weeks' gestation. The spleen was not seen on ultrasonographic examination in either fetus, suggesting polysplenia/asplenia syndrome. Both infants died shortly after delivery and the autopsies confirmed this diagnosis. Recommendations for sonographic screening of the fetal spleen in cases of prenatal detection of complex heart disease or cardiac dysrhythmia are discussed.

Abnormalities, Multiple↗

Comparison of gemfibrozil and clofibrate on serum lipids in familial combined hyperlipidemia. A randomized placebo-controlled, double-blind, crossover clinical trial.

A randomized double blind, placebo-controlled crossover design was used to determine the efficacy of gemfibrozil and clofibrate in the treatment of familial combined hyperlipidemia and to determine which one of these agents would be more effective. Sixteen patients, 12 men and 4 women, mean age 49.5 years (40-68 yrs), had the entry criteria of increased cholesterol and/or triglyceride with an increase in triglyceride and/or cholesterol in one or more first degree relatives and/or family history of premature cardiovascular disease. Patients received 6 weeks of placebo followed by clofibrate 1000 mg bid or gemfibrozil 600 mg bid for 12 weeks, placebo for 6 weeks and the other drug for 12 weeks. Plasma total cholesterol, triglycerides, HDL-C, LDL-C, apo B and apo A-I were measured every 6 weeks during the study. Gemfibrozil was associated with a significant (P less than 0.05) decrease in plasma triglyceride concentration compared to placebo but it was not significantly different compared to clofibrate. For ease of comparison, the mean value for serum triglycerides during gemfibrozil treatment (average of the 6 and 12 week measurements) was calculated and was 232 +/- 198 mg/dl (mean +/- 1 SD) compared to the average of the placebo treatment values of 381 +/- 410 mg/dl and the average value during the clofibrate treatment period of 217 +/- 178 mg/dl. HDL-C was significantly (P less than 0.05) increased with both drugs and to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Initiation of bacteriophage P22 DNA packaging series. Analysis of a mutant that alters the DNA target specificity of the packaging apparatus.

Bacteriophage P22 is thought to package its double-stranded DNA chromosome from concatemeric replicating DNA in a "processive" sequential fashion. According to this model, during the initial packaging event in such a series the packaging apparatus recognizes a nucleotide sequence, called pac, on the DNA, and then condenses DNA within the coat protein shell unidirectionally from that point. DNA ends are generated near the pac site before or during the condensation reaction. The opposite end of the mature chromosome is created by a cut made in the DNA after a complete chromosome is condensed within the phage head. Subsequent packaging events on that concatemeric DNA begin at the end generated by the headful cut of the previous event and proceed in the same direction as the previous event. We report here the identification of a consensus nucleotide sequence for the pac site, and present evidence that supports the idea that the gene 3 protein is a central participant in this recognition event. In addition, we tentatively locate the portion of the gene 3 protein that contacts the pac site during the initiation of packaging.

Base Sequence↗

Controlling for cerebral atrophy in positron emission tomography data.

This article outlines a simple method for estimating the degree of cerebral atrophy and subsequent experimental control for the effects of cerebral atrophy on regional metabolic values measured with positron emission tomography. It is suggested that rather than correcting derived values for atrophy, less potential error is introduced by experimentally controlling for regional atrophy when possible. By treating the derived metabolic rates and the measure of atrophy as two separate variables, it is also possible to establish whether there actually is a demonstrable relationship between the two measures.

Adolescent↗

Hypoalphalipoproteinemia resembling fish eye disease.

A 16-year-old boy presented with bilateral arcus cornealis and markedly decreased plasma high density lipoprotein cholesterol. The plasma lipoprotein abnormalities, as well as decreased mass and activity of lecithin:cholesterol acyltransferase (LCAT), were similar to those described in patients with fish eye disease. Increased number of target cells and decreased osmotic fragility of the proband's erythrocytes were noted. The proband's father and one of his brothers showed intermediate plasma lipoprotein and LCAT alterations. The father's erythrocytes also showed abnormal osmotic fragility. The mother of the propositus had normal plasma lipoproteins and erythrocyte osmotic fragility, but her LCAT activity was also low. Many of these features suggest a disorder similar to fish eye disease which is clinically and biochemically distinct from other hypoalphalipoproteinemias.

Adolescent↗

Interaction of high density lipoprotein with adipocytes in a new patient with Tangier disease.

A 56-year-old man, the offspring of a consanguineous first cousin marriage, presented with clinical, morphological, and biochemical features of familial deficiency of high-density lipoproteins (Tangier disease). Of 8 first- and second-degree relatives examined, 4 had either plasma apo A-I or HDL cholesterol concentrations 2 standard deviations below normal population mean on at least 1 occasion. The patient and a majority of his relatives also had high plasma apo B concentrations relative to their levels of cholesterol. Adipose tissue biopsy was undertaken to study HDL interaction with the patients' cells. Specific uptake of HDL3 was demonstrated in adipocytes of this patient, but was decreased relative to a control of similar fat cell size. However, no marked difference in fat cell cholesterol content was observed between the Tangier patient and the control. Thus it appears unlikely that adipocytes play a role in the etiology of Tangier disease.

Adipose Tissue↗

Plasmid vectors useful in the study of translation initiation signals.

The construction and characterization of plasmid vectors useful in the analysis of translation initiation signals in Escherichia coli and in the construction of lacZ gene hybrids are described. Transcription on the vectors proceeds from a cAMP-independent lac promoter through several restriction sites into a truncated lacZ structural gene lacking its first eight codons. Because this gene has no translation initiation signal, its level of expression is extremely low. A DNA fragment containing a translation start signal can be inserted between the promoter and truncated lacZ gene to produce a hybrid protein with functional beta-galactosidase activity. The vectors described here differ in sequence between the EcoRI cloning site and the lacZ gene to allow easy, in-frame joining of DNA containing a translation initiation signal to the lacZ gene. Cells containing plasmids can be screened directly for in-frame inserts by colony color on indicator plates.

Genetic Vectors↗

Bacteriophage L: chromosome physical map and structural proteins.

Restriction endonuclease cleavage site mapping was used to locate the regions of highest sequence homology in the chromosomes of Salmonella typhimurium bacteriophages L and P22. These lie in the DNA packaging, tail, early transcription antitermination, and perhaps integration "gene modules." Other regions of the two genomes are substantially less closely related. Phage L, which has no functional immunity I region, lacks approximately 1300 bp of DNA when compared to P22 in this section of the chromosome. At least some of the virion structural proteins are interchangeable between the two phages, which suggests that the two phage structural protein genes are very closely related. In addition, the apparent molecular weights of most P22 and L phage structural proteins are very similar. However, the phage L virion contains about 140 molecules of a 15K capsid protein which apparently has no P22 analog.

Chromosome Mapping↗

Additional restriction endonuclease cleavage sites on the bacteriophage P22 genome.

We present complete restriction endonuclease cleavage site maps of the bacteriophage P22 chromosome for 16 enzymes with six base recognition sequences, thereby positioning 116 new sites on the chromosome. Twenty-four such restriction maps for P22 DNA, containing 162 sites, have now been completed, and three enzymes were found that did not cut P22 DNA. Our results are consistent with the ideas that ClaI does not cleave the methylated recognition sequence ATCGA(me)T or A(me)TCGAT and StuI does not cleave the methylated recognition sequence AGGCC(me)T.

Base Sequence↗

On the sequential packaging of bacteriophage P22 DNA.

Bacteriophage P22 is thought to package daughter chromosomes serially along concatemeric DNA. We present experiments which show that the average DNA packaging series length increases with time after infection, which supports this model. In addition, we have analyzed the effect on average series length of lowering the amount of the various individual proteins involved in DNA packaging. These results support the notion that the protein products of gene 2 and gene 3 are both more stringently required for initiation of sequential DNA packaging series than for their extension, and they are compatible with a model for the control of series length in which that length is determined, at least in part, by a competition between series initiation events and extension events.

Coliphages↗

Q fever endocarditis: a report of 2 cases.

Two patients with Q fever endocarditis are described. Both patients demonstrated some of the characteristic features of Q fever endocarditis, i.e. the long course of the disease before diagnosis, persistently negative blood cultures, resistance to conventional antibiotic therapy and a dramatic response to tetracycline therapy. Complications included arteriovenous thrombo-embolism and hepatic enlargement, and 1 patient developed an immune complex form of glomerulonephritis. The possibility of Q fever endocarditis should be considered in all patients with infective endocarditis in whom blood cultures are negative and who fail to respond to conventional antibiotic therapy.

Adult↗

The fetal hydantoin syndrome. A case report.

A patient with the fetal hydantoin syndrome is described. The features include mild to moderate mental deficiency, craniofacial anomalies, prenatal onset of growth deficiency and varying limb abnormalities. Recognition of this spectrum of abnormalities in an infant should raise the possibility of maternal ingestion of hydantoin during pregnancy. The dangers of therapy with this drug during pregnancy are emphasized.

Abnormalities, Drug-Induced↗

Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts.

Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were acitve in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls.

Animals↗