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K L West

Publications and source records attributed to K L West.

11 recordsLinked to original sources
PubMed2000

Mutagenesis of E477 or K505 in the B' domain of human topoisomerase II beta increases the requirement for magnesium ions during strand passage.

A type II topoisomerase is essential for decatenating DNA replication products, and it accomplishes this task by passing one DNA duplex through a transient break in a second duplex. The B' domain of topoisomerase II contains three highly conserved motifs, EGDSA, PL(R/K)GK(I/L/M)LNVR, and IMTD(Q/A)DXD. We have investigated these motifs in topoisomerase II beta by mutagenesis, and report that they play a critical role in establishing the DNA cleavage-religation equilibrium. In addition, the mutations E477Q (EGDSA) and K505E (PLRGKILNVR) increase the optimal magnesium ion concentration for strand passage, without affecting the Mg(2+) dependence of ATP hydrolysis. It is likely that the binding affinity of the magnesium ion(s) specifically required for DNA cleavage has been reduced by these mutations. The crystal structure of yeast topo II indicates that residues E477 and K505 may help to position the three aspartate residues of the IMTD(Q/A)DXD motif for magnesium ion coordination, and we propose two possible locations for the magnesium ion binding site(s). These observations are consistent with a previous model in which the B' domain is positioned such that these acidic residues lie next to the active site tyrosine residue. A magnesium ion bound by these aspartate residues could therefore mediate the DNA cleavage-religation reaction.

Adenosine Triphosphate↗
PubMed2000

Concentrations of progesterone in milk from bottlenose dolphins during different reproductive states.

There are few published reports of an alternative, less invasive method than blood sampling to obtain reproductive hormone concentrations from captive dolphins. The aims of this study were to: (1) validate milk as an effective alternative to blood plasma for determining progesterone concentrations; and (2) utilize milk samples collected frequently to obtain progesterone concentration profiles and determine reproductive status. During the course of this study 16 plasma/milk sample pairs were collected from four adult bottlenose dolphins to correlate plasma and milk concentrations of progesterone. Milk samples were also collected approximately weekly for 4-5 months during three independent lactational periods. Additionally, milk samples were collected daily for approximately 1 year during three other independent lactational periods. A highly significant correlation was found between progesterone concentrations in plasma and milk (r(2) = 0.91, P < 0. 01). Progesterone contained in milk whey, fat, and solids were 3.95 +/- 1.3, 8.5 +/- 1.1, and 52.0 +/- 0.6%, respectively. Progesterone profiles from milk samples collected from two dolphins during 1995 indicated pregnancies (with progesterone concentrations between 8 and 46.5 ng/ml) which resulted in parturition. High progesterone concentrations in a third dolphin that did not give birth indicated a possible pseudopregnancy or fetal resorption. A possible ovulation not resulting in pregnancy was evident in one female in 1998, follicular activity in another female in 1998, and a year-long anestrous period in the third animal studied in 1998. It is confirmed that dolphins can become pregnant while lactating and that the approximate time of conception is identifiable in milk profiles, illustrating the potential application of this method in pregnancy detection and reproductive monitoring.

Anestrus↗
PubMed2000

Histone H1 is a specific repressor of core histone acetylation in chromatin.

Although a link between histone acetylation and transcription has been established, it is not clear how acetylases function in the nucleus of the cell and how they access their targets in a chromatin fiber containing H1 and folded into a highly condensed structure. Here we show that the histone acetyltransferase (HAT) p300/CBP-associated factor (PCAF), either alone or in a nuclear complex, can readily acetylate oligonucleosomal substrates. The linker histones, H1 and H5, specifically inhibit the acetylation of mono- and oligonucleosomes and not that of free histones or histone-DNA mixtures. We demonstrate that the inhibition is due mainly to steric hindrance of H3 by the tails of linker histones and not to condensation of the chromatin fiber. Cellular PCAF, which is complexed with accessory proteins in a multiprotein complex, can overcome the linker histone repression. We suggest that linker histones hinder access of PCAF, and perhaps other HATs, to their target acetylation sites and that perturbation of the linker histone organization in chromatin is a prerequisite for efficient acetylation of the histone tails in nucleosomes.

Acetylation↗
PubMed1999

Human DNA topoisomerase IIbeta binds and cleaves four-way junction DNA in vitro.

We have used gel retardation analysis to show that human DNA topoisomerase IIbeta can bind a 40 bp linear duplex containing a single DNA topoisomerase IIbeta cleavage site. Furthermore, we demonstrate for the first time that human DNA topoisomerase IIbeta binds to four-way junction DNA. This supports previous suggestions that topoisomerase II may be targeted to supercoiled DNA through the recognition of DNA cruciforms, helix-helix crossovers and hairpins. DNA topoisomerase IIbeta had a 4-fold higher affinity for the four-way junction than for the linear duplex, as demonstrated by protein titration and competition analysis. Furthermore, the DNA topoisomerase IIbeta:four-way junction complex was significantly more salt stable than the complex with linear DNA. The four-way junction contained potential topoisomerase IIbeta cleavage sites straddling the points of strand exchange, and indeed, topoisomerase IIbeta was able to cleave three of these four predicted sites. This indicates that topoiso-merase IIbeta can bind to the centre of the junction. Topoisomerase II has to bind both the transported and the gated DNA helices prior to strand passage, and it is possible that both helices are provided by the four-way junction in this case. The stable complex of DNA topoisomerase IIbeta with four-way junction DNA may provide an ideal substrate for further studies into the mechanism of substrate recognition and binding by DNA topoisomerase II.

Base Sequence↗
PubMed1988

The impact of education about schizophrenia on relatives varying in expressed emotion.

The demand for information by relatives and the success of family intervention programs with an initial didactic component has resulted in a proliferation of educational interventions in schizophrenia. The present study assesses the impact of a single educational session on relatives of recent-onset schizophrenic patients. Results suggest that relatives who participated in family education experience an increased sense of support from the treatment team and a nearly significant tendency toward a decrease in self-blame regarding the schizophrenic illness. Despite findings in previous studies suggesting information acquisition immediately after education and retention after 6 months, the present study found no information retention after a 2-month period. After family education, relatives rated as high in expressed emotion (EE) reported a significantly increased sense of understanding of the illness and expressed increased feelings of support from the treatment team, whereas low EE relatives did not change significantly in these attitudes as a function of the educational session. Low EE relatives demonstrated more actual information about the illness and were less likely to perceive the symptoms as being done intentionally to bother them.

Adult↗
PubMed1988

The subacute hospital treatment of the borderline patient. II: An integrated focus on splitting.

A psychiatric inpatient unit with expertise in family treatment has developed an integrated effort to provide a one to three month treatment program for hospitalized borderline patients. Treatment goals are more ambitious than those obtainable by simple crisis intervention. Appreciation of staff splitting is enhanced by an intergenerational family systems approach. Early and sustained focus on splitting is aided by the use of a 15 minute educational tape and a weekly therapy group required for all nonpsychotic patients and recommended for their families. Cases illustrating the family perspective and a group therapy session are presented in detail. The therapy group, run by an interdisciplinary team (the authors) requires active staff initiative and confrontation to avoid responsibility-evading patient coalitions. Diagnostic considerations and impact of the program on patients and on staff are discussed.

Adult↗
PubMed1981

Parental communication deviance and affective style. Predictors of subsequent schizophrenia spectrum disorders in vulnerable adolescents.

In an attempt to assess the contributory role of family factors to the development of schizophrenia-like disorders, measures of parental communication deviance and affective styles of communication were obtained for a sample of families of disturbed but nonpsychotic adolescents. Outcome was assessed five years later. Absence of a pathologic affective style was associated with a benign outcome, but neither parental variable alone allowed precise identification of the schizophrenia-spectrum cases. However, an index using a combination of both variables was statistically predictive of subsequent psychiatric status at follow-up. Thus, adolescents whose parents had both a pathologic affective style of communication and a high level of communication deviance had schizophrenia-like disorders develop in young adulthood. Adolescents of parents who had both lower levels of communication deviance and a benign affective style had offspring with healthier outcomes.

Adolescent↗
PubMed1977

Parental transactional style deviance as a possible indicator of risk for schizophrenia.

The presence of a pattern of parental transactional style deviance on the Thematic Apperception Test (TAT) (a significant attribute of parents of offspring with schizophrenia spectrum disorders) was used to identify a group of disturbed nonpsychotic adolescents hypothesized to be at high risk for subsequently developing schizophreniform psychopathology. High-risk male adolescents came from two symptom groups, withdrawn adolescents and adolescents in active family conflict, which are symptom patterns similar to the premorbid pictures of two schizophrenia subtypes. High-risk parents also tended to show transactional style deviance in direct interaction with their child and in a written statement describing their child's problem. The degree of risk was significantly related to the amount of therapy in which the family was subsequently engaged and, at a four-year follow-up, to the level of adjustment of the adolescents seen earlier in the project.

Adolescent↗
PubMed1970

Ethylene oxide resistance of nondesiccated and desiccated spores of Bacillus subtilis var. niger hermetically sealed in various polymeric films.

The resistance to destruction of spores of Bacillus subtilis var. niger hermetically sealed in various polymeric films and exposed to ethylene oxide with and without relative humidity was determined. The effect of desiccation was also determined. The order of increased resistance to sterilization with regard to type of polymeric film was found to be: polyethylene equal to polyvinyl chloride, less than nylon, less than cellophane/polyethylene laminate, less than phenoxy, less than mylar/polyethylene laminate. Desiccated spores sealed in various polymeric films were much more resistant to ethylene oxide sterilization than nondesiccated spores. Relative humidity was an important factor in ethylene oxide sterilization with spores not sealed in polymeric films. However, with spores hermetically sealed in polyethylene, added relative humidity was an insignificant factor in the sterilization process.

Bacillus subtilis↗