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Biomedical subjects

K Fletcher

Publications and source records attributed to K Fletcher.

At least 19 recordsLinked to original sources
PubMed2000

A mathematical model for assessing changes in neurofilament protein levels in neurites and cell bodies of differentiating neuroblastoma cells.

A mathematical model which allows the calculation of the level of neurofilament protein in the cell body (x) and in the neurites (y) of differentiating SK-N-SH cells is presented. The model considers the changes in cell number (proliferating cells) and the number of cells with neurites (differentiating cells). It takes into account the fact that (i) when cells are cultured in differentiating conditions, an increase in cell number is initially observed and (ii) in a non-synchronized population of differentiating cells, the length of neurite extended by individual cells varies within the population. Total neurofilament protein levels in a population of cells were measured by enzyme-linked immunoabsorbant assay and application of the model to the data allowed values for x and y to be calculated. The validity of the model is supported by the fact that the predicted total neurofilament protein levels are highly correlated with the experimentally derived neurofilament protein levels. The model should be of use in temporal studies of cytoskeletal proteins involved in neuronal growth/differentiation and also in studies in which the system is a target of toxic insult.

Cell Differentiation↗
PubMed2000

Multimethod psychoeducational intervention for preschool children with disruptive behavior: two-year post-treatment follow-up.

This paper describes the 2-year post-treatment follow-up of preschool children identified as having high levels of disruptive behavior at kindergarten entry. They were assigned to four treatment conditions: A no-treatment group, parent-training only, treatment classroom only, and the combination of parent training with the treatment classroom. Interventions lasted the entire kindergarten academic year. Initial post-treatment results reported previously indicated no effects for the parent-training program but some efficacy for the classroom intervention program. For this report, the disruptive behavior (DB) children were subdivided into those who did (n = 74) and did not (n = 77) receive the treatment classroom. Two-year post-treatment follow-up results indicated no differences between the classroom treated and untreated DB groups. These groups also failed to differ in the percentage of children using available treatments across the follow-up period. The DB children in both groups had significantly more symptoms of ADHD and ODD than a community control group (N = 47) at follow-up. They also received higher ratings of externalizing problems on the parent Child Behavior Checklist, more severe ratings of behavior problems at home, and ratings of more pervasive behavior problems at school, and had poorer academic skills. Results suggested that early intervention classrooms for DB children may not produce enduring effects once treatment is withdrawn, and that better approaches are needed for identifying those DB children at greatest risk for later maladjustment.

Attention Deficit and Disruptive Behavior Disorder↗
PubMed2000

Multi-method psycho-educational intervention for preschool children with disruptive behavior: preliminary results at post-treatment.

Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive, hyperactive, impulsive, and inattentive behavior. These "disruptive" children were randomly assigned to four treatment conditions lasting the kindergarten school year: no treatment, parent training only, full-day treatment classroom only, and the combination of parent training with the classroom treatment. Results showed that parent training produced no significant treatment effects, probably owing largely to poor attendance. The classroom treatment produced improvement in multiple domains: parent ratings of adaptive behavior, teacher ratings of attention, aggression, self-control, and social skills, as well as direct observations of externalizing behavior in the classroom. Neither treatment improved academic achievement skills or parent ratings of home behavior problems, nor were effects evident on any lab measures of attention, impulse control, or mother-child interactions. It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening, it may not be a useful approach to treating the home and community behavioral problems of such children. The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children. Even so, most treatment effects were specific to the school environment and did not affect achievement skills. These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions.

Achievement↗
PubMed1999

EGF-Induced receptor autophosphorylation in primary hepatocytes isolated from phenobarbitone-treated mice.

Phenobarbitone (PB) treatment of mice causes a decrease in the growth factor responsiveness of hepatocytes. Here, epidermal growth factor receptor (EGFR) expression and receptor autophosphorylation was determined in hepatocytes isolated from control and PB-treated mice. There was a decrease in the level of EGFR expression in hepatocytes isolated from mice following PB administration when compared to controls. EGF caused an approximate 20-fold increase of the 170 kD phosphotyrosine band in control hepatocytes, which was inhibited by the EGFR specific tyrosine kinase inhibitor 4, 5-dianilinopthalamide. Following PB treatment, the degree of basal receptor phosphorylation (in the absence of EGF) was significantly greater and therefore the fold rise in EGFR phosphorylation in isolated hepatocytes was lower than in controls. However, the overall extent of EGF-induced receptor phosphorylation was not diminished in hepatocytes isolated from PB-treated mice. Therefore the reduction in responsiveness to growth factors seen in hepatocytes ex vivo or the cessation of proliferation observed in vivo following PB administration is unlikely to be attributed to a decrease in ligand binding and subsequent receptor autophosphorylation.

Animals↗
PubMed1999

The perceptions and practices of pediatricians: tobacco intervention.

OBJECTIVES: To investigate pediatrician self-reported intervention practices related to tobacco use and cessation. We queried about practices with three groups 1) children/adolescents who do not smoke; 2) children/adolescents who smoke; and 3) parents, and the relationship of counseling practices with the personal and professional practice-related factors of pediatricians. DESIGN: Mailed anonymous survey regarding their self-reported tobacco use prevention and cessation intervention practices. POPULATION: Random sample of 350 pediatricians in one state. RESULTS: A response rate of 75% was achieved. Pediatricians reported the greatest counseling practice in encouraging children/adolescents to not start smoking, followed by counseling adolescents who smoke. The lowest practice score was for intervening with parents who smoke. The age, gender, site of practice (eg, HMO, solo practice), and subspecialty status of the pediatricians were not related to practice. Pediatricians who reported at least some community involvement in local tobacco control efforts reported significantly higher levels of smoking cessation counseling with both children and adolescents and with parents who smoke. Pediatricians who reported previous training in counseling about tobacco issues also reported significantly higher levels of counseling of both adolescent smokers and parents who smoke but not of children and adolescents who do not smoke. Higher role perception, believing that smoking cessation counseling provided by pediatricians can be effective, and self-efficacy, were predictive of intervention with all three groups. The perceived barriers scale was not related to intervention with any group. CONCLUSIONS: Pediatricians are missing opportunities to help their patients to stop smoking and to prevent smoking initiation. Pediatricians are intervening least frequently with parents who smoke. Practices should be tailored to the specific target group.

Adolescent↗
PubMed1999

Hepatic gene mutations induced in Big Blue rats by both the potent rat liver azo-carcinogen 6BT and its reported noncarcinogenic analogue 5BT.

The potent rat liver carcinogen 6-p-dimethylaminophenylazobenzthiazole (6BT) and its reported noncarcinogenic analogue 5-p-dimethylaminophenylazobenzthiazole (5BT; evaluated for carcinogenicity under the similar limited bioassay conditions used for 6BT) have been studied in order to seek an explanation for their different carcinogenic activities. Both compounds act as DNA-damaging agents to the rat liver, and both have now been shown to induce lacI (-) gene mutations in the liver of Big Blue(trade mark) transgenic rats. Both compounds were mutagenic following ten daily gavage doses or following administration in diet for 10 days. Neither chemical induced cell proliferation in the liver following repeat gavage administrations. In contrast, dietary administration of 6BT, and to a lesser extent of 5BT, induced hepatic cell proliferation. The carcinogen 6BT, but not the noncarcinogen 5BT, caused proliferation of oval stem cells in the livers by both routes of administration. It is possible that mutations induced in oval cells by 6BT are responsible for its potent carcinogenicity, and that the comparative absence of these cells in 5BT-treated livers may account for the carcinogenic inactivity of 5BT. Equally, the proliferation of the oval cells may reflect changes in liver homeostasis associated with the liver toxicity observed at the dose level of 6BT used (which was, nonetheless, the dose level used in the positive cancer bioassays). It is concluded that the new data presented cannot explain the differing carcinogenic activities of 5BT and 6BT, and that the reported noncarcinogen 5BT may also be carcinogenic when adequately assessed for this activity.

Animals↗
PubMed1998

Mutagenicity of the human bladder carcinogen 4-aminobiphenyl to the bladder of MutaMouse transgenic mice.

The human carcinogen 4-aminobiphenyl (4AB) was evaluated in the MutaMouse transgenic mouse mutation assay. A single oral dose of 75 mg/kg induced 6.9-, 1.8- and 2.2-fold increases in the mutation frequency (MF) in the bladder, liver and bone marrow, respectively. Ten daily oral doses of 10 mg/kg 4AB increased the MF in the bladder, liver and bone marrow by 13.7-, 4.8- 2.4-fold the control value, respectively. The repeat dosing protocol was therefore more sensitive than the single dose protocol. Assessment of DNA samples prepared from pooled liver homogenates clearly indicated the increase in MF observed in the individual liver samples obtained from both groups of 4AB-treated mice.

Aminobiphenyl Compounds↗
PubMed1998

Psychiatric and psychological morbidity as a function of adaptive disability in preschool children with aggressive and hyperactive-impulsive-inattentive behavior.

Children with high levels of aggressive-hyperactive-impulsive-inattentive behavior (AHII; n = 154) were subdivided into those with (n = 38) and without (n = 116) adaptive disability (+AD/-AD) defined as a discrepancy between expected versus actual adaptive functioning. They were compared to each other and a control group of 47 normal children. Both AHII groups were more likely to have attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder than control children; more symptoms of general psychopathology; greater social skills deficits; more parental problems; and lower levels of academic achievement skills. Compared to AHII - AD children, AHII + AD children had (1) more conduct disorder; (2) greater inattention and aggression symptoms; (3) more social problems, less academic competence, and poorer self-control at school; (4) more severe and pervasive behavior problems across multiple home and school settings; and (5) parents with poorer child management practices. Thus, adaptive disability has utility as a marker for more severe and pervasive impairments in AHII children.

Achievement↗
PubMed1998

Mutagenicity of ethyl carbamate to lacZ- transgenic mice.

The mutagenicity of the rodent carcinogen ethyl carbamate (EC, urethane) has been assessed using the lacZ- transgenic mouse mutation assay (Muta Mouse). In two separate experiments a single i.p. dose of 900 mg/kg urethane followed by a 14-16 day expression period yielded statistically significant (approximately 2-fold) increases in mutation frequency (MF) in the lung and liver of the mice. In the second experiment MF in the spleen and bone marrow was also assessed and statistically significant increases in MF were observed in each case. Concomitantly conducted bone marrow micronucleus assays gave 15.8- and 8-fold increases respectively in the incidence of micronucleated polychromatic erythrocytes in the two studies.

Animals↗
PubMed1998

The geriatric resource nurse model of care: a vision for the future.

The geriatric resource nurse model of care is an innovative and effective method of integrating high quality, evidence-based geriatric nursing care into a clinical practice setting. The model creates expert bedside clinicians who recognize the vulnerability of older adults, who proactively educate and serve as consultants for peers, and who role model best practice geriatric nursing. This article describes the history and key features of this nursing model of care delivery with examples of how it was successfully implemented in a variety of hospitals around the country.

Aged↗
PubMed1997

Lack of activity of estradiol in rodent bone marrow micronucleus assays.

Estradiol has been evaluated in five independent rodent bone marrow micronucleus assays and has been found to be inactive. The dose-range evaluated extended from three daily doses of 20 micrograms/kg to the rat, a regimen that elicited a potent uterotrophic response from the animals, to single doses of between 10-150 mg/kg to the mouse. The mouse assays simulated and extended the conditions of test employed by earlier investigators who had found estradiol, and three structurally-related synthetic estrogens, to be active in mouse micronucleus assays over the dose range 1-10 mg/kg. It is concluded that estradiol is not genotoxic to the bone marrow of rodents. The top dose-level used in the present micronucleus assays (150 mg/kg) represented approximately 150,000 times the minimum estrogenic dose of this chemical to rodents, and that was considered to be above the dose at which useful genetic toxicity data would be generated for this potent estrogen. The maximum tolerated dose (MTD) of estradiol to rodents remains to be established.

Animals↗
PubMed1997

The response of hepatocytes isolated from phenobarbitone treated mice to mitogenic growth factors.

The ability was investigated of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) to stimulate DNA synthesis in hepatocytes isolated from C57B1/6J mice following 1, 3, 7, 30 and 90 days pre-treatment with the hepatomegalic drug, phenobarbitone (PB). A 3-fold increase in S-phase labelled hepatocytes was observed in the absence of growth factors after 3 days treatment with PB, which was not seen at other investigated time points. This suggests that the proliferative influence present in vivo at this time interval is maintained in the ex vivo model. Maximum labelling indices of > 5-fold the unstimulated control value were observed in hepatocytes isolated from control and 1 day PB pre-treated mice when cultured in the presence of 5 or 10 ng/ml EGF or HGF. Hepatocytes isolated from 3, 7, 30 or 90 day treated mice showed a considerably reduced responsiveness to growth factors; maximum labelling indices did not exceed by a factor of 2 the value obtained in the absence of growth factors. However, the apparent decrease in responsiveness to growth factors in hepatocytes isolated from 3 day pre-treated mice was due to an increased background level of proliferation and the attainment of a 'ceiling level' of DNA synthesis at approx. 35%. DNA synthesis was not further enhanced by addition of both EGF and HGF. This maximal level of stimulation may indicate that only a specific hepatocyte sub-population is capable of responding to growth factors under the conditions employed. The loss in sensitivity to mitogenic stimuli after 7 days PB pre-treatment correlates with a reported decrease in receptor protein and mRNA levels in rats and coincides with the in vivo shift from hyperplasia to hypertrophy.

Animals↗
PubMed1996

The mitogenic response to EGF of rat hepatocytes cultured on laminin-rich gels (EHS) is blocked downstream of receptor tyrosine-phosphorylation.

Hepatocytes cultured on type I collagen proliferate in response to mitogenic growth factors yet de-differentiate. By contrast, hepatocytes on laminin-rich gels (EHS) demonstrate stable differentiated functions, while DNA synthesis is negligible. Here we have confirmed that this lack of proliferation was not due to deterioration of the cells because albumin release was maintained for several weeks. Additionally it does not appear to be due to the presence of the growth inhibitor TGF beta within the gel since and anti-TGF beta antibodies did not reverse the growth blockade. The addition of EGF to cells cultured on either type I collagen or EHS gel induced increased tyrosine phosphorylation of a 180kDa protein which ran in a position identical to that of the EGF receptor detected by a specific EGF receptor antibody. We conclude that since functional EGF receptors were present, the mitogenic response of hepatocytes on EHS gels is blocked at some downstream signaling event beyond that of receptor tyrosine autophosphorylation.

Animals↗
PubMed1996

Use of restraints in the elderly.

Chronologic age older than 65 years is a predictor for restraint use in the acute care setting. The therapeutic effect of restraints has not been established. Geriatric patients in the hospital are more vulnerable to the risks associated with physical and chemical restraints. A framework is presented to guide the clinician in the decision making process on restraint use. Nursing homes have been successful in the implementation of restraint reduction programs, and these models might be reviewed for applicability to the acute care setting.

Accreditation↗
PubMed1995

Three-year follow-up and clinical implications of a mindfulness meditation-based stress reduction intervention in the treatment of anxiety disorders.

A previous study of 22 medical patients with DSM-III-R-defined anxiety disorders showed clinically and statistically significant improvements in subjective and objective symptoms of anxiety and panic following an 8-week outpatient physician-referred group stress reduction intervention based on mindfulness meditation. Twenty subjects demonstrated significant reductions in Hamilton and Beck Anxiety and Depression scores postintervention and at 3-month follow-up. In this study, 3-year follow-up data were obtained and analyzed on 18 of the original 22 subjects to probe long-term effects. Repeated measures analysis showed maintenance of the gains obtained in the original study on the Hamilton [F(2,32) = 13.22; p < 0.001] and Beck [F(2,32) = 9.83; p < 0.001] anxiety scales as well as on their respective depression scales, on the Hamilton panic score, the number and severity of panic attacks, and on the Mobility Index-Accompanied and the Fear Survey. A 3-year follow-up comparison of this cohort with a larger group of subjects from the intervention who had met criteria for screening for the original study suggests generalizability of the results obtained with the smaller, more intensively studied cohort. Ongoing compliance with the meditation practice was also demonstrated in the majority of subjects at 3 years. We conclude that an intensive but time-limited group stress reduction intervention based on mindfulness meditation can have long-term beneficial effects in the treatment of people diagnosed with anxiety disorders.

Adult↗
PubMed1989

Molecular cloning of DNA sequences from cervical intraepithelial neoplasia that hybridize to human cytomegalovirus DNA.

We have prepared EMBL3 libraries of DNA extracted from the cervix of a patient with cervical intraepithelial neoplasia (CIN) and isolated seven recombinant clones containing sequences that hybridize to human cytomegalovirus (HCMV) DNA. Restriction analysis of one clone with BamHI and SalI endonucleases revealed that the insert DNA showed a high degree of homology to the HCMV Ad169 genome over the region between the HindIII K/E site and the SalI site located within the BamHI P fragment. The HCMV insert in the CIN clone is integrated and flanked by cellular sequences. The major immediate early gene that encodes a polypeptide of approximately 69 kD was found to be conserved in the CIN clone. Transfection of clones encoding the immediate early region of HCMV resulted in cells that were positive in immunofluorescence studies with two monoclonal antibodies directed against the HCMV 69 kD immediate early polypeptide. Infection of human ectocervical cells with HCMV Ad169 revealed that they could express the 69 kD polypeptide encoded by the immediate early gene but could not replicate the virus, whereas HCMV was able to replicate productively in cultured endocervical cells. HCMV has been shown to activate endogenous retroviruses and also to transcriptionally activate the long terminal repeat of human immunodeficiency virus. Activation of virus and cellular genes by HCMV may be a means by which this virus is involved in the multistage process of oncogenesis and/or the activation of latent infections.

Animals↗