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Biomedical subjects

J D Allen

Publications and source records attributed to J D Allen.

At least 37 records · Page 2Linked to original sources
PubMed1999

The mouse Bcrp1/Mxr/Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin.

Mouse fibroblast cell lines lacking functional Mdr1a, Mdr1b, and Mrp1 genes were selected for resistance to topotecan, mitoxantrone, or doxorubicin. Each of the resulting drug-resistant lines showed marked gene amplification of Bcrp1, the mouse homologue of the human ATP-binding cassette transporter gene BCRP/MXR/ABCP, and greatly elevated expression of Bcrp1 mRNA. All three of the resistant cell lines were highly cross-resistant to topotecan and mitoxantrone and, to a variable extent, doxorubicin. All showed greatly reduced cellular accumulation and greatly increased efflux of mitoxantrone that was dependent on cellular ATP and efficiently reversed by the compound GF120918. The mouse Bcrp1 cDNA encodes a 657-amino-acid protein with 81% identity (86% similarity) to the human breast cancer resistance protein (BCRP) and a virtually superimposable hydrophobicity profile. Our data argue strongly that mouse Bcrp1 is functionally comparable with human BCRP, conferring multidrug resistance to topotecan, mitoxantrone, doxorubicin, and related compounds. Mouse models and cell lines should, therefore, be highly informative in understanding the clinical, pharmacological, and physiological roles of BCRP.

3T3 Cells↗
PubMed1999

Beliefs about Papanicolaou smears and compliance with Papanicolaou smear follow-up in adolescents.

OBJECTIVE: To explore qualitatively adolescent girls' understanding of Papanicolaou smears and barriers to compliance with Papanicolaou smear follow-up appointments. DESIGN: Qualitative analysis, using 3 focus groups and 15 in-depth, semistructured individual interviews. SETTING: Adolescent Clinic and Young Parents' Program at Children's Hospital, Boston, Mass. MAIN OUTCOME MEASURES: Beliefs and attitudes about Papanicolaou smears and barriers to compliance with Papanicolaou smear follow-up. RESULTS: The mean (+/- SD) age of the 15 interview participants was 18.7 (+/- 1.9) years. Knowledge about Papanicolaou smears and pelvic examinations was poor. Most participants believed that their peers receive Papanicolaou smear screening and perceived teenagers to be susceptible to cervical cancer. Perceived benefits to getting Papanicolaou smears were prevention and early detection or diagnosis, and reported barriers included pain or discomfort, embarrassment, fear of finding a problem, fear of the unknown, denial, poor communication or rapport with the provider, not wanting to look for trouble, lack of knowledge, and peers' advice. Participant-generated strategies for how providers could overcome barriers to Papanicolaou smear screening included education and the development of trusting, consistent relationships with providers. Participant-generated strategies for how providers could enhance appointment-keeping among adolescents included telephone and written reminders. CONCLUSIONS: These data support a behavioral theory-based model of adolescent compliance with Papanicolaou smear follow-up, which may help to develop strategies to enhance compliance with Papanicolaou smear follow-up appointments. These strategies include providing in-depth education about Papanicolaou smears, addressing barriers to Papanicolaou smear follow-up, focusing on appropriate provider behaviors, and instituting an appointment reminder system.

Adolescent↗
PubMed1999

The relationship between social network characteristics and breast cancer screening practices among employed women.

This study examined the relationship between social network characteristics and breast cancer screening practices among employed women. We hypothesized that larger social networks, higher levels of support from networks, and stronger social influences to undergo screening would be positively associated with regular utilization of mammograms and clinical breast examinations. Data were collected from women aged 52 and over who were employed in 27 worksites (N = 1,045). Social network characteristics, breast cancer screening practices, and sociodemographic factors were assessed in a self-administered survey. Bivariate analyses revealed that social influences were significantly associated with regular screening; social support was only marginally associated with regular screening; and social network size was not at all associated. In multivariate analyses, only the perception that screening is normative among one's peers was predictive of regular screening. Provider recommendation was the single most potent predictor of regular screening. These findings provide support for the importance of social norms in motivating women to adhere to screening guidelines. In addition, they underscore the potent impact of provider recommendations on women's screening practices.

Aged↗
PubMed1999

Effect of microcurrent stimulation on delayed-onset muscle soreness: a double-blind comparison.

OBJECTIVE: To examine the efficacy of microcurrent electrical neuromuscular stimulation (MENS) treatment on pain and loss of range of motion (ROM) associated with delayed-onset muscle soreness (DOMS). DESIGN AND SETTING: We assigned subjects to 1 of 2 groups. Group 1 received treatment with microcurrent stimulation (200 muA, 30 Hz, for 10 minutes, then 100 muA, 0.3 Hz, for 10 minutes) 24, 48, and 72 hours after DOMS induction. Group 2 served as a sham group and was treated using a machine altered by the manufacturer so that no current could flow through the electrodes. SUBJECTS: DOMS was induced in the biceps brachii of the nondominant arm of 18 subjects (3 males, 15 females: age = 20.33 +/- 2.3 years, ht = 170.81 +/- 7.3 cm, wt = 69.61 +/- 13.1 kg). Dominance was defined as the arm used by the subject to throw a ball. MEASUREMENTS: Subjective pain and active elbow extension ROM were evaluated before and after treatment each day. Two methods were used to assess pain: constant pressure using a weighted Orthoplast sphere and full elbow extension to the limit of pain tolerance. Subjective pain was measured with a graphic rating scale and active elbow extension ROM using a standard, plastic, double-armed goniometer. Three repeated-measures ANOVAs (between-subjects variable was group, within- subjects variables were day and test) were used to assess ROM and pain scores for the 2 groups. RESULTS: We found no significant difference in the measurement of subjective pain scores or elbow extension ROM when the MENS group was compared with the sham group. CONCLUSIONS: Our results indicate that the MENS treatment, within the parameters used for this experiment, was not effective in reducing the pain or loss of ROM associated with delayed-onset muscle soreness.

Journal Article↗
PubMed1998

Topographic differences in CNV amplitude reflect different preparatory processes.

Topographic differences in Contingent Negative Variation (CNV) were recorded while people were preparing for cognitive versus motor tasks in an S1-S2 paradigm. CNV had a frontal distribution when people prepared to encode words into long-term memory, whereas CNV was more centrally distributed when the tasks were predominantly motoric. These topographic differences appeared to be related to the type of task rather than the amount of information extracted from the S2, because a direct manipulation of the level of S2 processing had little effect on CNV amplitude. The topographic differences in CNV suggest that preparation for motor activity is a different psychological process from preparation for stimulus processing and that these two processes are subserved by different neural structures. This experiment also demonstrated that a recognition memory paradigm can be useful in the investigation of the psychological correlates of CNV.

Adolescent↗
PubMed1998

Functional dissociation of the prefrontal cortex and the hippocampus in timing behavior.

Using the peak procedure, rats with aspiration lesions to the medial prefrontal cortex (PFC) or the hippocampus were tested for the acquisition of timing behavior and temporal memory. After surgery, rats were 1st trained to discriminate a 40-s interval and then tested for temporal memory with gap trials. Results indicated that lesions to the medial PFC disrupted the acquisition of timing behavior. Medial PFC animals needed significantly more trials to reach criterion, and their temporal discrimination function was less uniform and steep, indicating a general deficit in timing ability. In hippocampal rats, the ability to estimate the duration of the discriminative stimulus was unaffected by the lesion. It was concluded that the hippocampus is not necessary for the acquisition of timing behavior in this task. Gap trials failed to produce a deficit in the memory for temporal events for either lesion. Thus, it was further concluded that neither the medial PFC nor the hippocampus is necessary for the memory of temporal events.

Analysis of Variance↗
PubMed1998

Ginseng supplementation does not enhance healthy young adults' peak aerobic exercise performance.

OBJECTIVE: To determine the short term effects (21 days) of 200 mg (7% standardized) Panax ginseng supplementation vs. placebo on peak aerobic exercise performance in healthy young adults, with unrestricted diets. METHODS: Twenty men and eight women (age = 23.2 +/- 3.2 years, height = 175.8 +/- 8.6 cm; weight = 75.2 +/- 15.3 kg) were randomly assigned to either a Panax ginseng or placebo group for a period of 3 weeks in a double blind design. Prior to and following treatment the subjects performed a symptom limited graded exercise test on a Schwinn Airdyne ergometer. The data were analyzed using an analysis of variance. RESULTS: No significant treatment effect was observed for the dependent variables of VO2, exercise time, workload, plasma lactate and hematocrit at peak levels, or for heart rate and rate of perceived exertion at 150 watts, 200 watts and peak. CONCLUSIONS: The results of this study do not support an ergogenic effect on peak aerobic exercise performance following a 3-week supplementation period of 200 mg 7% Panax ginseng in healthy young adults with moderate exercise capacities and unrestricted diets.

Adult↗
PubMed1998

Intention to have a mammogram in the future among women who have underused mammography in the past.

This study investigated associations between confidence in one's ability to discuss mammography with health providers and to obtain regular mammograms (self-efficacy), social network members' attitudes toward mammograms (social influence), mammography experiences, and intention to have a mammogram in the next 1 to 2 years among women who were not in adherence with screening guidelines. Data were collected as part of a baseline assessment for a work site intervention study. Women 52 years and older completed a self-administered survey. Those not in compliance with screening guidelines (n = 194) were included in the analyses. Logistic regression revealed that self-efficacy and strong supportive social influences were significantly associated with mammography intention (odds ratio [OR] = 2.50, OR = 2.22, respectively), adjusting for prior mammography use. Findings suggest that interventions designed to promote mammography should build women's confidence in their ability to discuss mammography with health providers and to obtain regular mammograms. Intervention among social networks may also be an effective means of promoting mammography.

Adult↗
PubMed1997

Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-myc.

Evidence from proviral tagging experiments has suggested that pim-2 is similar in oncogenic behavior to its well characterized relative pim-1. While the basal expression in tissues differs, both genes are highly expressed in mitogenically stimulated hematopoietic cells and their transcription is induced in response to the same cytokines. Expression of a pim-2 transgene in lymphoid cells predisposed mice to T-cell lymphomas like those promoted by pim-1 transgenes. Moreover, strong collaboration with an E mu-myc transgene was manifested as pre-B cell leukemia in neonate bi-transgenic animals. Remarkably, this collaboration was attenuated but not prevented by X-inactivation of one of the transgenes. The addition of pim-2 to the fold increases the prominence of the pim proto-oncogene family in tumorigenesis.

Age Factors↗
PubMed1997

Vasopressin and memory. I. The vasopressin analogue AVP4-9 enhances working memory as well as reference memory in the radial arm maze.

The present study examined the effects of vasopressin on memory. Healthy rats were injected with the arginine vasopressin fragment AVP4-9 and the AVP antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Et-Pyr 2,Val4,Arg8] and were tested in an eight-arm radial maze for 60 sessions. All injections were given s.c. 30 min prior to testing. AVP4-9 enhanced radial arm maze performance. AVP4-9 treated animals showed enhancement in performance as well as increases in the rate of learning, indicating that they learned the task faster. Furthermore, the overall memory enhancement was due to improved working memory as well as to improved reference memory. These results cannot be explained in terms of changes in locomotor activity because an open field test revealed no differences between groups for both of these compounds. The AVP antagonist did not impair performance in the radial maze. It is concluded that AVP4-9 has a more general effect on memory, one that is not limited to a specific type of memory.

Animals↗
PubMed1997

Vasopressin and memory. II. Lesions to the hippocampus block the memory enhancing effects of AVP4-9 in the radial maze.

Previous work has shown that the arginine vasopressin fragment AVP4-9 enhanced overall performance in the radial arm maze. This enhancement effect was due to improved working memory as well as to improved reference memory. The present study uses a behavioral approach to investigate whether these effects of vasopressin on memory are mediated by the hippocampus. Animals received either NMDA lesions to the hippocampus or sham operations and were then treated with AVP4-9 or saline. The testing was performed in an eight-arm radial maze for 60 sessions, and all injections were given s.c. 30 min prior to testing. The hippocampal lesioned animals showed a marked deficit in working memory that was not ameliorated by AVP4-9; however, the improvement in reference memory produced by the compound was as large as in healthy animals. Since the AVP treatment did not differentiate between the two hippocampal groups, the memory enhancing effects of AVP4-9 were blocked by hippocampal lesions. It is concluded that vasopressin has a more general effect on memory and that its site of action includes but is not limited to the hippocampus.

Animals↗
PubMed1997

Rounded biphasic waveform reduces energy requirements for transvenous catheter cardioversion of atrial fibrillation and flutter.

We postulated that reducing peak leading edge shock voltage and its rate of rise (waveform rounding) would reduce energy requirements for cardioversion of AF and AFl, and may therefore reduce patient discomfort. Transvenous defibrillating catheters (In-Control Inc.) were placed in the RAA (active fixation) and the CS of six anesthetized sheep. AF or AFl was induced by electrical stimulation (100 Hz, 2 V; Grass stimulator). A standard trapezoidal biphasic (S) waveform (3-ms duration each phase) was compared with a similar waveform that had the first phase rounded (R). Cardioversion was attempted after 30 seconds of arrhythmia, using a Ventritex HVS-O2 defibrillator modified to allow waveform rounding. Each waveform was randomly tested several times at 100-, 150-, and 200-V leading edges, and percentage cardioversion success calculated. Shock energy was calculated from delivered current and voltage using Flukeview (Fluke, Inc.) software. At 100-V leading edge R (64% success) and S (59%), shocks were similarly efficacious (P = 0.37). However, R delivered less current, voltage, and energy than the comparable S shock (means 1.30 A, 65.0 V, 0.33 J R vs 1.92 A, 94.2 V, 0.47 J S; P = 0.0001). Both waveforms were equally successful at 150 V (88% vs 100%; P = NS) and 200 V (100% vs 100%), but again R delivered less current, voltage, and energy (2.05 A, 102.5 V, 0.82 J R vs 2.78 A, 142.3 V, 1.11 J S at 150 V; 2.76 A, 141.2 V, 1.58 J R vs 3.77 A, 189.4 V, 2.03 J S at 200 V; both P = 0.0001). No arrhythmic or other complications occurred in the 174 shocks delivered. Waveform rounding reduces delivered peak voltage, current, and energy without reducing defibrillation efficacy. To determine if these changes are associated with a reduction in discomfort, patients with AF are currently being cardioverted with these waveforms during electrophysiological studies.

Animals↗
PubMed1997

Is the hippocampus involved in temporal discrimination and the memory of short intervals?

Rats with lesions to the hippocampus proper and the subiculum were tested for timing behavior and temporal memory. Using the peak procedure, they were trained to discriminate a 40 s interval and a retention gap tested the memory for time. Results were interpreted within the theoretical framework of the internal clock and with respect to current theories on hippocampal function. Timing behavior was unaffected by either lesion and no shifts in the temporal discrimination functions were observed. The lesions also failed to show a deficit in the memory for temporal events. For all groups, the retention gap increased the mean peak time by the time of the gap. This indicated that all rats used the stop rule which required the use of working memory. Thus, it was concluded that the hippocampus is neither necessary for accurate timing behavior nor for the memory of temporal events.

Animals↗
PubMed1996

Complementation tagging of cooperating oncogenes in knockout mice.

Gene disruption and overexpression in mice can be combined with proviral tagging to investigate the biochemical pathways in which oncogenes act. The phenomenon of oncogene collaboration permits a focussed genetic approach analogous to the strategies employed in suppressor screens in invertebrates and yeast. We illustrate here its application to investigating the action of the pim kinases in tumorigenesis. However, it should be possible to utilize this strategy for dissecting a much wider range of biochemical pathways in mammalian systems.

Animals↗
PubMed1996

Effects of selective dopamine D1- and D2-agonists and antagonists on timing performance in rats.

Dopamine (DA) D1- and D2-agonists and antagonists were administered at fixed doses to assess putative dopaminergic involvement in timing behavior in rats performing under a peak-interval schedule. Significant shifts in response distributions to the left (consistent with the overestimation of the passage of time) were observed after treatment with the D1- and D2-agonists SKF 38393 and quinpirole, respectively. Both DA antagonists, eticlopride (D2) and SCH 23390 (D1), shifted the response distributions to the right (consistent with the underestimation of the passage of time), but neither drug produced statistically significant shifts. Based on percent shift in peak time from predrug baseline values, no significant differences were detected between agents as a function of their reported affinities for the D1- or D2-receptors. Results indicate the need for a systematic evaluation of each drug at various doses and a more detailed examination of the use of temporal schedules in predicting the efficacy of psychotherapeutic agents.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Temporomandibular joint range of motion: a ratio of interincisal opening to excursive movement in a healthy population.

Range of motion is used in the examination and diagnosis of many joints. A simple method to measure and record temporomandibular joint range of motion is presented. Correlation of mandibular movement to excursive or lateral movements for a healthy population is described. The maximum incisal opening and lateral movements of 75 subjects, aged 20-50 years, were recorded. The average of maximum opening to lateral movements was found to be 4.4 to 1. A significant correlation or ratio of mandibular movement for use in diagnoses and treatment planning is discussed.

Adult↗
PubMed1996

Effects of blockade of fast and slow inward current channels on ventricular fibrillation in the pig heart.

OBJECTIVE: To determine the contribution of fast and slow inward channels to the electrocardiogram (ECG) of ventricular fibrillation. METHODS: Ventricular fibrillation was induced by endocardial electrical stimulation in pigs anaesthetised with pentobarbitone sodium (30 mg/kg intravenously). ECGs simultaneously recorded from the body surface (lead II) and from the endocardium were studied by power spectrum analysis (0-40 Hz). RESULTS: The mean (SEM) dominant frequency of fibrillation (9.0 (1.1) Hz in lead II at 0-40 s) did not change significantly with time in pigs given intravenous saline. However, the dominant frequency was significantly reduced by intravenous pretreatment with the class I antiarrhythmic drugs, lignocaine (3 mg/kg, 6.5 (0.5) Hz; 10 mg/kg, 4.2 (0.6) Hz), mexiletine (3 mg/kg, 6.2 (0.4) Hz; 10 mg/kg, 5.5 (0.4) Hz), and disopyramide (2.5 mg/kg, 5.4 (0.6) Hz). After flecainide (3 mg/kg, 6.9 (0.5) Hz) the reduction in frequency was not significant. Similar data were obtained with endocardial recordings. In contrast pre-treatment with verapamil (0.2 mg/kg, 11.7 (0.8) Hz; and 1.0 mg/kg, 12.9 (1.6) Hz) produced a significantly higher dominant frequency of fibrillation than saline and widened the bandwidth of frequencies around the dominant frequency. CONCLUSIONS: These results indicate that voltage-dependent sodium channel currents contribute to the rapid frequencies of ventricular fibrillation. Blockade of L-type inward calcium channel activity increases the fibrillation frequency and fractionates the frequencies of the fibrillation wavefronts.

Animals↗