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L M Johnson

Publications and source records attributed to L M Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Specific repression of the yeast silent mating locus HMR by an adjacent telomere.

The yeast silent mating loci HML and HMR are located at opposite ends of chromosome III adjacent to the telomeres. Mutations in the N terminus of histone H4 have been previously found to derepress the yeast silent mating locus HML to a much greater extent than HMR. Although differences in the a and alpha mating-type regulatory genes and in the cis-acting silencer elements do not appear to strongly influence the level of derepression at HMR, we have found that the differential between the two silent cassettes is largely due to the position of the HMR cassette relative to the telomere on chromosome III. While HML is derepressed to roughly the same extent by mutations in histone H4 regardless of its chromosomal location, HMR is affected to different extends depending upon its chromosomal positioning. We have found that HMR is more severely derepressed by histone H4 mutations when positioned far from the telomere (cdc14 locus on chromosome VI) but is only minimally affected by the same mutations when integrated immediately adjacent to another telomere (ADH4 locus on chromosome VII). These data indicate that the degree of silencing at HMR is regulated in part by its neighboring telomere over a distance of at least 23 kb and that this form of regulation is unique for HMR and not present at HML. These data also indicate that histone H4 plays an important role in regulating the silenced state at both HML and HMR.

Binding Sites↗
PubMed1993

Pharmacokinetics of the enantiomers of verapamil in the dog.

The intravenous (0.5 mg/kg) and oral (5 mg/kg) dose kinetics of verapamil were studied in 6 dogs during steady-state oral verapamil dosing (5 mg/kg every 8 h for 3 days). Racemic verapamil and norverapamil, a metabolite of verapamil, were quantitated in plasma by HPLC-fluorescence detection. The verapamil peaks eluting off the column were collected and rechromatographed on an Ultron-OVM column, which resolved the two verapamil enantiomers. After intravenous administration, the systemic clearance and apparent volume of distribution of (-)-(S)-verapamil were nearly twice that of the (+)-(R)-isomer. There was no difference in the elimination half-lives between the two isomers. After oral administration, the oral clearance of (-)-(S)-verapamil was 20 times that of the (+)-(R)-isomer. The apparent bioavailability of (+)-(R)-verapamil was over 14 times that of (-)-(S)-verapamil. The plasma protein binding of the (+)-(R)-isomer was slightly higher by 5% than (-)-(S)-verapamil; however, this effect was not enough to account for the difference between the apparent volume of distribution of the enantiomers, indicating that the tissue binding of (-)-(S)-verapamil was greater than that of the (+)-(R)-isomer. This data on the disposition of the enantiomers of verapamil in the dog is similar to that reported for man and demonstrates that the dog may be an appropriate animal model for man in future studies on the disposition of the enantiomers of verapamil.

Administration, Oral↗
PubMed1993

Neurosarcoidosis with unusual MRI findings.

This 53-year-old white male presented with a 4-month-history of weakness and pain. Despite an initial partial response to steroid therapy, his neurologic deterioration progressed culminating in paraparesis, paresthesias, urinary incontinence, altered mentation and a 20 lb weight loss. A gadolinium-enhanced MRI study showed a pattern suggestive of perivascular involvement. A subsequent cerebral biopsy was diagnostic for neurosarcoidosis.

Brain↗
PubMed1992

Identification of a non-basic domain in the histone H4 N-terminus required for repression of the yeast silent mating loci.

We have shown previously that a stretch of four charged residues (16-19) at the histone H4 N-terminus is involved in repression of the yeast silent mating loci. One of these residues, Lys16, is a site for acetylation, which may prevent repression of the silent mating loci. In this paper we ask whether other sequences in histone H4, possibly in conjunction with H3 residues, are required for repression. We find that even in combination, the other seven acetylatable lysines in H3 and H4 do not function in repression. In contrast, we have found that an adjacent relatively uncharged domain (residues 21-29) is required for repression and that single amino acid insertions and deletions in this region are extremely detrimental. We propose that the basic and non-basic domains together form a DNA (or protein) induced amphipathic alpha-helix required in the formation of a repressive chromatin structure.

Acetylation↗
PubMed1992

Airway changes in relationship to mandibular posturing.

Comparison of posterior airway space was evaluated radiographically on patients with sleep apnea in a mandibular reposed position vs. a mandibular protruded position. This was performed at the Santa Barbara Sleep Disorders Medical Center to simulate the effect of anterior orthotic appliances on these patients. The overall effect of forward mandibular posturing was a mean increase of posterior airway space (PAS) by approximately 56%, but wide variations were seen.

Cephalometry↗
PubMed1991

Central arteriovenous malformations of the maxillofacial skeleton: case report.

Central arteriovenous malformation of the maxillofacial skeleton, though rare, is a well-documented entity. Past treatments have usually included some form of surgical intervention. Surgical resection as an attempt to cure has been effective but costly, ie, in relationship to patient morbidity and hospital expenditures. A case of vascular malformation is presented in which selective angiography and embolization as a primary treatment were used rather than ablative surgery. The patient tolerated the procedures well, with complete resolution of bleeding.

Adult↗
PubMed1991

The effects of schedule history and the opportunity for adjunctive responding on behavior during a fixed-interval schedule of reinforcement.

The effects of schedule history and the availability of an adjunctive response (polydipsia) on fixed-interval schedule performance were investigated. Two rats first pressed levers under a schedule of food reinforcement with an interresponse time greater than 11 s, and 2 others responded under a fixed-ratio 40 schedule. All 4 were then exposed to a fixed-interval 15-s schedule. Water was continuously available under these conditions, but after responding became stable on the fixed-interval schedule, access was experimentally manipulated. With water freely available, subjects did not display characteristic fixed-interval response rates and patterns (i.e., scalloping or break-and-run). Instead, they exhibited predictable, stable patterns of behavior as a function of their schedule histories: Subjects with the interresponse-time history exhibited low response rates, and those with the fixed-ratio history exhibited high rates. Manipulating the amount of water available resulted in marked changes in response rates for rats with the interresponse-time history but not for those with the fixed-ratio history. The results illustrate the multiple causation of behavior by its previous and current schedules of reinforcement and other concurrent factors.

Animals↗
PubMed1990

Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae.

Repression of transcription from the silent mating loci (HML alpha and HMRa) is essential for mating ability in Saccharomyces cerevisiae. This silencing is known to require at least five proteins (SIR1, SIR2, SIR3, SIR4, and histone H4) and is accompanied by a change in chromatin structure. We show here that four positions of histone H4 (N-terminal residues 16, 17, 18, and 19) are crucial to silencing. HML alpha and HMRa are efficiently repressed when these positions are occupied by basic amino acids but are derepressed when substituted with glycine. These results suggest that acetylation of Lys-16 would lead to derepression of the silent mating loci. Three strong extragenic suppressors of the latter H4 mutations were isolated and determined to be located in SIR3. These suppressors allow high mating efficiencies in cells expressing either wild-type H4 or H4 containing single amino acid substitutions. They did not allow efficient mating in a strain that contained an H4 N-terminal deletion. These results indicate that the SIR3 mutations do not bypass the requirement for the H4 N terminus but, rather, allow repression in the presence of a less than optimal H4 N terminus. This provides a link between one of the SIR proteins and a component of chromatin.

Amino Acid Sequence↗
PubMed1988

An inverse relationship between baseline fixed-interval response rate and the effects of a tandem response requirement.

Previous experiments examining the effects of adding a tandem fixed-ratio response requirement on fixed-interval schedule performance have reported inconsistent results. One variable that may account for such inconsistencies is the baseline response rate in the fixed-interval condition. This possibility was investigated in the present study. Rats were given histories with either interresponse times greater than 11 s or fixed-ratio 40 schedules of reinforcement, which engendered either relatively low or high rates of responding, respectively, in the subsequent fixed-interval condition. A tandem ratio response requirement (fixed-ratio 9) was then introduced. The effects of adding this tandem response requirement were inversely related to the baseline fixed-interval response rates; low rates of responding in the fixed-interval condition were markedly increased, whereas high rates of responding were relatively unaffected. This inverse relationship appears to be similar to the rate-dependent relations observed in behavioral pharmacology. These results may provide an explanation for the inconsistent findings reported in previous studies on tandem fixed-interval fixed-ratio schedules and suggest that principles of behavioral pharmacology research may be applicable to the study of the effects of nonpharmacological variables on schedule-controlled behavior.

Animals↗