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Biomedical subjects

M A Watson

Publications and source records attributed to M A Watson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Three-site synapsis during Mu DNA transposition: a critical intermediate preceding engagement of the active site.

The chemical steps of bacteriophage Mu DNA transposition take place within a higher order nucleoprotein structure. We describe a novel intermediate that precedes the previously characterized transpososomes and directly demonstrates the interaction of a distant enhancer element with recombination regions. The transpositional enhancer interacts with the Mu left and right ends to form a three-site synaptic (LER) complex. Under normal reaction conditions, the LER complex is rapidly converted into the more stable Mu transpososomes. However, mutation of the Mu terminal nucleotides results in accumulation of the LER and a failure to form the type 0 transpososome. During the transition from LER to type 0, the Mu DNA termini and the active site of the transposase engage in a catalytically competent conformation.

Bacteriophage mu↗
PubMed1996

Rate and selectively of synapsis of res recombination sites by Tn3 resolvase.

Site-specific recombination catalysed by Tn3 resolvase requires the formation of an intermediate synaptic complex containing two res recombination sites and several resolvase subunits. Synaptic complexes were observed directly by chemical crosslinking of resolvase subunits followed by agarose gel electrophoresis. The highest yield of synaptic complex was from a "standard" substrate, a supercoiled plasmid with res sites in direct repeat, but complexes were also made between sites in inverted repeat, or in nicked or linear molecules, or in separate molecules. The substrate selectivity for synapsis is less stringent than for recombination; thus recombination selectivity is dependent on steps after synapsis. The stability of the synapse after its formation might be a key factor, since unproductive synapses are less stable than productive ones. In a standard substrate, synapsis is fast relative to the rate of recombination. Crosslinking in active reaction mixtures yields synaptic complexes derived from both the substrate and the catenane recombination product. Although catalysis of strand exchange is at binding site I of res, a pair of isolated site 1's do not synapse, whereas a synaptic complex is formed from a plasmid carrying two copies of res binding sites II and III. Our data are consistent with a model in which the formation of the synaptic intermediate is driven, and its structure defined, by the initial interaction of these accessory sites.

Cross-Linking Reagents↗
PubMed1996

Mammaglobin, a mammary-specific member of the uteroglobin gene family, is overexpressed in human breast cancer.

In this report, we describe a novel cDNA isolated from a primary human breast adenocarcinoma and differentially expressed in several breast carcinoma cell lines. The protein encoded by this cDNA, which we have named mammaglobin, is homologous to a family of secreted proteins that includes rat prostatic steroid-binding protein subunit C3, human Clara cell 10-kilodalton protein, and rabbit uteroglobin. Expression of the mammaglobin gene is restricted to the adult mammary gland. More significantly, in an analysis of 35 breast tumor biopsies, mammaglobin mRNA levels were increased at least 10-fold relative to normal breast tissue in 23% of cases. The breast-specific expression of this potentially secreted protein and its frequent overexpression in primary human breast tumors suggest that mammaglobin may be a novel marker for the management of breast cancer.

Adult↗
PubMed1996

Inadequate history as a barrier to immunization.

OBJECTIVES: To evaluate how lack of immunization history contributes to missed opportunities for immunization and to document the effort required to obtain immunization history. DESIGN: Cross-sectional. SETTING: Urban, inner-city primary care pediatric clinic serving a low-income, multiethnic population. PATIENTS: Ninety-five new patients seen for either well-child care (53 patients) or acute illnesses (42 patients) during a 4-month period in 1993. Fifty-nine patients were aged 3 to 59 months and 36 were aged 5 to 15 years. MEASUREMENTS: Efforts to obtain immunization history were documented by means of a standardized data collection form. RESULTS: Immunization history was obtained for only 26 (27%) of 95 patients during the initial visit. Caregivers of 74 (78%) of 95 patients did not bring immunization records to the initial visit; they were no more likely to bring records for well-child care than for acute care or for younger vs older children. Parents brought immunization records more often than did nonparents. A total of 145 telephone calls were made and 30 letters were sent in an attempt to obtain immunization histories. Immunization records were never found for 10 new patients (11%). Thirty-two patients (34%) were found to be lacking immunizations. Of these, only three patients had contraindications to immunization at the initial visit. Therefore, in one third of our new patients, opportunities to immunize were missed solely because their immunization records were unavailable at the initial visit. In another one third of cases, caregivers had incorrectly believed their child's immunizations to be up to date. CONCLUSIONS: Opportunities to immunize children were often missed because of a lack of immunization history. Our experience supports the need for improved documentation of immunization histories.

Adolescent↗
PubMed1996

Treatment of postrenal transplant erythrocytosis. Long-term efficacy and safety of angiotensin-converting enzyme inhibitors.

Fifty-two patients with postrenal transplant erythrocytosis were treated with an angiotensin-converting enzyme inhibitor (lisinopril or enalapril) for a median of 13 months (range 0-44). A significant fall in haemoglobin of 1.8 +/- 1.6 g dl-1 (range - 0.8 to 6.6) occurred over the first 3 months (p < 0.0001). The haemoglobin then remained stable for as long as 3 years. Both enalapril and lisinopril were equally effective. Therapy was withdrawn in 16 patients (31%) because of decline in renal function (6), anaemia (5), hypotension (3), hyperkalaemia (1) or erectile impotence (1) - complications which were all reversible. Angiotensin-converting enzyme inhibitors in low dose are a safe and effective long-term therapy for postrenal transplant erythrocytosis.

Adult↗
PubMed1996

Race, quality of care, and antipsychotic prescribing practices in psychiatric emergency services.

OBJECTIVE: The study examined whether the prescription practices of clinicians in psychiatric emergency services differed for African-American patients. Prescription of antipsychotic medications and its relation to quality of care was a particular focus. METHODS: Data from 442 independently observed evaluations of patients in psychiatric emergency services were examined using multivariate analyses. The observations were made during a five-year period at four urban general hospitals in California. RESULTS: Clinicians in the four emergency services, most of whom were Caucasian, prescribed more psychiatric medications to African Americans than to other patients and devoted significantly less time to their evaluations. African Americans received more oral doses and more injections of antipsychotic medications, and the mean 24-hour dosage of antipsychotics (1,321 milligrams) was significantly higher than for other patients (825 milligrams). The tendency to overmedicate African-American patients was lower when clinicians' efforts to engage the patients in treatment were rated higher. CONCLUSIONS: The results highlight the importance of efforts to engage African Americans in the treatment process and the need for clinical skills and training to help bridge cultural distances.

Adult↗
PubMed1996

Quality of care and use of less restrictive alternatives in the psychiatric emergency service.

OBJECTIVE: The study examined factors affecting clinicians' decisions in the psychiatric emergency service about referring patients to less restrictive alternatives to inpatient care. Indicators of quality of care and the severity of the patient's condition were a particular focus. METHODS: Trained mental health professionals observed the evaluations of 425 patients in seven California county general hospitals. Multivariate modeling was used to examine variables thought to predict disposition to alternative care. RESULTS: Less restrictive alternatives were available for 61 percent of the 425 patients and were used for 39 percent; they were overlooked by clinicians in 14 percent of cases and considered but not used in 8 percent. Patients' need for a controlled hospital setting, as indicated by the severity of their condition, was most important in determining use of hospital alternatives. Quality of care, especially the clinician's ability to engage patients in treatment at a level appropriate to their functioning, was also a significant predictor of whether alternative care was considered or used. CONCLUSIONS: Under managed care, clinicians are under extreme economic pressure to use less restrictive alternatives, thereby reducing costly inpatient care. To ensure quality of care in general hospital emergency services, the development of supervised hospital alternatives is crucial. Clinicians should be encouraged to engage patients in treatment if appropriate use of alternative care is a goal.

Adolescent↗
PubMed1996

Vectors encoding alternative antibiotic resistance for use in the yeast two-hybrid system.

We have altered the antibiotic resistance of the reporter plasmids and the pJG4-5 activation-domain and pEG202 DNA binding-domain plasmids used in the Brent interaction trap/two-hybrid system. These plasmids were each previously ampicillin-resistant, resulting in an inefficient purification of any one plasmid from a yeast strain containing all three plasmids that constitute the complete interaction trap. By creating derivatives of each of these plasmids expressing either kanamycin or chloramphenicol resistance, along with the parent plasmids, we now have the option to use the interaction trap in yeast with three E. coli differentially selectable vectors. This will allow isolation of any one plasmid by purifying all of the interaction trap plasmids from yeast simultaneously and plating E. coli transformed with the plasmids onto the appropriate antibiotic plate to select the particular plasmid of interest.

Ampicillin Resistance↗
PubMed1995

Regulation of neurotensin receptor mRNA expression by the receptor antagonist SR 48692 in the rat midbrain dopaminergic neurons.

In this study, we demonstrated that the tyrosine hydroxylase-like immuno-reactive (possibly dopaminergic) neurons express neurotensin receptor mRNA in the rat substantia nigra and in the ventral tegmental area. Additionally, 2 weeks treatment with the neurotensin receptor antagonist SR 48692 increased mRNA levels in the substantia nigra. These data suggest that neurotensin receptor expression in the perikarya and in the terminal regions of dopaminergic neurons is regulated by its endogenous agonist in vivo.

Animals↗
PubMed1995

N-acetylbenzidine and N,N'-diacetylbenzidine formation by rat and human liver slices exposed to benzidine.

The extent to which N-acetylbenzidine and N,N'-diacetylbenzidine are formed may influence benzidine-induced carcinogenesis. This study compared the formation of these metabolites by rat and human liver slices. The relationship between the NAT2 genotype and the formation of these acetylated products was also evaluated in humans. In rat liver slices incubated with 0.05 mM [3H]benzidine for 1 h (n = 3), N-acetylbenzidine and N,N'-diacetylbenzidine represented 8.8 +/- 3.6 and 73 +/- 2.5% respectively of the total radioactivity recovered by HPLC. No unmetabolized benzidine was observed. This suggests that an equilibrium exists between benzidine, N-acetylbenzidine and N,N'-diacetylbenzidine in rat liver slice incubations which favors N,N'-diacetylbenzidine formation. In the presence of 0.1 mM paraoxon, a deacetylase inhibitor, N-acetylbenzidine and N,N'-diacetylbenzidine increased to 13 +/- 0.6 and 79 +/- 0.3% respectively. Within 2 h after incubating human liver slices with 0.014 mM [3H]benzidine (n = 8), benzidine, N-acetylbenzidine and N,N'-diacetylbenzidine represented 19 +/- 5, 34 +/- 4 and 1.6 +/- 0.5%, respectively, of the total radioactivity recovered by HPLC. Thus in the human, conditions in liver slices favor N-acetylbenzidine rather than N,N'-diacetylbenzidine formation. With paraoxon, benzidine, N-acetylbenzidine and N,N'-diacetylbenzidine represented 2 +/- 0.4, 24 +/- 4 and 51 +/- 3%, respectively. This resulted in a 32-fold increase in N,N'-diacetylbenzidine formation. Individuals with rapid NAT2 genotypes formed 1.4-fold more N-acetylbenzidine than slow acetylators. However, this increase was not significant. There was no apparent correlation of N,N'-diacetylbenzidine formation with NAT2 genotype. Similar results were observed when human slices were incubated with 0.09 mM [3H]benzidine. Deacetylase, perhaps more than N-acetyltransferase, influences hepatic metabolism and subsequent carcinogenesis of benzidine in man. These results help explain the species and organ specificity of benzidine carcinogenesis.

Aged↗
PubMed1995

H-ras oncogene mutation spectra in B6C3F1 and C57BL/6 mouse liver tumors provide evidence for TCDD promotion of spontaneous and vinyl carbamate-initiated liver cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin which has been found to be non-genotoxic in short term in vitro tests but strongly carcinogenic in two stage models of hepatocellular carcinogenesis in female rats. Many recent studies have shown that after treatment of mice with various genotoxic or non-genotoxic compounds, the H-ras oncogene mutational patterns exhibited by hepatocellular tumors appear to vary specifically with the chemical. To gain insight into the mechanism of TCDD-associated carcinogenesis, susceptible B6C3F1 mice and resistant C57BL/6 mice were treated with a single dose of vinyl carbamate (VC) or vehicle, and TCDD was administered once every 2 weeks for 1 year to half of the animals in each group. Liver tumor prevalence was assessed and found to be highest in the VC + TCDD treatment groups, reaching nearly 100% at 600 days in both sexes and both strains of mice. DNA was isolated from 20 or more frozen liver tumors (if available) from each exposure group and analyzed for H-ras mutations in codon 61 by sequencing after PCR amplification of exon 2. Fifty-one percent of tumors analyzed from B6C3F1 mice treated with TCDD alone had H-ras codon 61 mutations with a pattern similar to that detected in spontaneous tumors. Seventy-eight percent of tumors from B6C3F1 mice treated with both VC and TCDD had codon 61 mutations, and most mutations were A-->T transversions in the second base as observed similarly with VC alone. In the C57BL/6 strain comparable results were found in the respective exposure groups. These data suggest that TCDD is acting as a promoter of lesions previously initiated either spontaneously or by VC. Moreover, the intrinsic resistance of both male and female C57BL/6 mice to liver tumor formation seemed to disappear after treatment with TCDD.

Animals↗
PubMed1995

Factors in the quality of patient evaluations in general hospital psychiatric emergency services.

OBJECTIVES: The study examined the usefulness of a three-perspective model for determining the quality of evaluations in psychiatric emergency services. The model was used to evaluate the hypothesis that the provision of high-quality care in emergency services is primarily influenced by service objectives related to patients' clinical characteristics rather than by institutional constraints, such as workload or physical facilities, or by social biases, such as clinicians' attitudes toward patients or perceptions of community expectations. METHODS: The evaluation of 683 persons assessed in nine California public facilities were independently observed. Multivariate techniques were used to test the relative importance of patients' clinical characteristics, possible sources of social bias among clinicians, and institutional constraints in influencing three quality-of-care dimensions: technical quality, the art of patient care, and optimum investment of time. RESULTS: The findings generally confirmed the hypothesis that patients' clinical characteristics have more influence on the quality of care provided than institutional constraints or social biases. However, one institutional constraint--increased workload demands--led to reduced technical quality and to less than optimal use of time. Further, social biases reflected in the clinician's like for and preconceptions about the patient also influenced the quality of their evaluations. CONCLUSIONS: The model is a useful tool for examining quality of care in the psychiatric emergency service. Increasing workload pressures negatively affect quality of care.

Attitude of Health Personnel↗
PubMed1995

The quality of psychiatric emergency evaluations and patient outcomes in county hospitals.

Quality of care is widely assumed to be related to patient outcomes, but little is known about care in relation to outcomes in county general hospital psychiatric emergency services. It was hypothesized that conformity to professional standards (technical quality) and engagement of the patient (artful care) in psychiatric emergency services evaluations would contribute to improved patient functioning (Global Assessment Scale score) and appropriate disposition. A total of 583 cases in seven facilities were analyzed. Conformity to technical standards of care was associated with retention even after constraints, biases, and admission criteria had been taken into account. Conversely, artful care was associated with lower probability of retention and improved functioning.

California↗
PubMed1995

Clinical utility of biochemical analysis of cerebrospinal fluid.

In addition to microbial culture, cytology, and immunological studies, physicians rely on the clinical chemistry laboratory for biochemical analysis of patients' cerebrospinal fluid (CSF). However, apart from routine glucose and protein determinations, the clinical value of other CSF analytes is often unclear. Here, we review the literature pertaining to the use of CSF biochemical measurements in managing patients with infectious disease, neoplasia, stroke and trauma, and dementia. Although a small number of studies demonstrate potential usefulness of some markers, we conclude that, without further study, the data are insufficient to support the routine clinical use of most of the analytes examined.

Central Nervous System Neoplasms↗
PubMed1994

Isolation of differentially expressed sequence tags from human breast cancer.

Identification of quantitative changes in gene expression that occur in the malignant mammary gland, if sufficiently characterized, may yield novel molecular markers which may be useful in the diagnosis and treatment of human breast cancer. Using modifications of a previously documented technique, the differential display polymerase chain reaction, we describe the isolation of differentially expressed sequence tags, short complementary DNA fragments corresponding to mRNAs that are differentially expressed in breast cancer biopsies, as compared to normal breast tissue controls. Direct sequencing and expression analysis of two sequence tags demonstrate that they represent sequences which are overexpressed in a number of breast carcinoma cell lines. A paradigm for generating a catalogue of these sequence tags is discussed.

Base Sequence↗
PubMed1994

p53 mutation hotspot in radon-associated lung cancer.

Mutations in gene p53 are the most common defects in lung cancer and may be a pathway through which environmental carcinogens initiate cancer. We investigated p53 mutations in lung cancers from uranium miners with high radon exposure. 16 (31%) of 52 large-cell and squamous-cell cancers from miners contained the same AGG to ATG transversion at codon 249, including cancers from 3 or 5 miners who had never smoked. This specific mutation has been reported in only 1 of 241 published p53 mutations from lung cancers. The codon 249 mutation may be a marker for radon-induced lung cancer.

Case-Control Studies↗
PubMed1994

Assignment of a locus for mouse lung tumor susceptibility to proximal chromosome 19.

Previous studies have hypothesized that at least three genetic loci contribute to differences in pulmonary adenoma susceptibility between mouse strains A/J and C57BL/6J. One gene that may confer susceptibility to lung tumorigenesis is the Kras protooncogene. To identify other relevant loci involved in this polygenic trait, we determined tumor multiplicity in 56 randomly chosen N-ethyl-N-nitrosourea-treated (A/J x C57BL/6J) N1 x C57BL/6 backcross (AB6N2) progeny and correlated it with genotypes at 77 microsatellite markers spanning the genome. A correlation of lung tumor multiplicity phenotypes with genotypes of microsatellite markers on distal Chromosome (Chr) 6 in the Kras region (Pas1) was confirmed, and a new region on Chr 19 (designated Pas3) was identified that also contributes to susceptibility. Linkage analysis on Chr 19 with 270 AB6N2 mice localized the region flanked by D19Mit42 and D19Mit19 that is most closely associated with lung tumor susceptibility. The Pas3 locus may be an enhancer of the susceptibility locus on Chr 6.

Adenoma↗