Search PubMed⌕ Search

Biomedical subjects

J Jackson

Publications and source records attributed to J Jackson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Polymeric micellar paclitaxel phosphorylates Bcl-2 and induces apoptotic regression of androgen-independent LNCaP prostate tumors.

BACKGROUND: Paclitaxel has been difficult to evaluate in preclinical tumor model systems because its poor solubility requires a Cremophor EL formulation, which results in lethal anaphylaxis. We tested the effectiveness of a novel polymeric micellar paclitaxel on androgen-independent tumor growth in the LNCaP tumor model. METHODS: Athymic male mice bearing LNCaP tumors were castrated and allowed to grow until their PSA levels increased to three times above precastration levels. The animals were then treated with 0.5 mg intravenous polymeric micellar paclitaxel once daily for the first 5 days of a 3-week cycle. In total, three cycles were given. Tumor volume and serum PSA levels were measured weekly to monitor tumor progression. RESULTS: In vitro mitogenic assays demonstrated that polymeric micellar paclitaxel was effective in inhibiting LNCaP cell growth with an IC(50) of 5 nM. Paclitaxel precipitated apoptosis in vitro at a concentration of 1 nm and higher, confirmed by DNA laddering. Western blotting demonstrated that paclitaxel treatment phosphorylated and inactivated Bcl-2. In mice bearing LNCaP tumors treated with micellar paclitaxel, tumors regressed rapidly with the commencement of micellar paclitaxel treatment. Tumor size decreased 91% and PSA level decreased 96% after three cycles of treatment. TUNEL immunostaining of the tumor treated with micellar paclitaxel showed marked apoptosis when compared with the control. No significant side effects or mortality was observed in the micellar paclitaxel group (n = 7). In contrast, all (n = 7) mice treated with conventional Cremophor EL paclitaxel died within 1 day of injection. CONCLUSIONS: The polymeric micellar paclitaxel formulation is water-soluble and capable of inducing complete response in mice bearing androgen-independent LNCaP tumors. The lack of toxicity of polymeric micellar paclitaxel permits in vivo preclinical testing of paclitaxel-based combination regimens.

Animals↗
PubMed2000

The good physician

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Locoregional first recurrence after mastectomy: prospective cohort studies with and without immediate chemotherapy.

PURPOSE: To evaluate prospectively the impact of combination chemotherapy in the combined modality treatment of isolated first locoregional recurrence (LRR) following mastectomy for breast cancer. METHODS AND MATERIALS: Between 1979 and 1989, 120 chemotherapy-naive women with isolated LRR as first failure after mastectomy were prospectively identified, uniformly staged, and systematically followed. Treatment consisted of excision if feasible, radical locoregional radiotherapy, and a hormonal maneuver (unless estrogen receptor negative). The initial chemotherapy cohort also received 8 cycles of doxorubicin and cyclophosphamide. This was compared to a subsequent control cohort. RESULTS: For all patients, the 10-year actuarial relapse-free survival +/- 95% confidence interval was 42.1+/-9.2%, and overall survival was 56.8+/-9.1%. No difference was seen in locoregional control between cohorts. At 5 years, distant recurrence-free survival for chemotherapy and control cohort respectively was 75.4+/-10.8% and 60.7+/-12.5% (p = 0.33) and overall survival was 81.9%+/-9.6 and 74.3%+/-11.2 (p = 0.24). Univariate analysis showed no prognostic importance for any imbalance between cohorts. Cox modeling confirmed that complete resection was strongly associated with fewer LRR (hazard ratio [HR] 0.32, p = 0.001) and also with better overall survival (HR 1.82, p = 0.019). Chemotherapy produced a substantial reduction in risk of death (HR 0.72 CI 0.421-1.235, p = 0.23). CONCLUSIONS: In this prospective but nonrandomized study of treatment for first LRR, the risk of death in the later control cohort was 1.39 times the risk in the chemotherapy cohort but failed to reach statistical significance. The results justify further study.

Adult↗
PubMed2000

Genetic variation within the ticks Ixodes holocyclus and Ixodes cornuatus from south-eastern Australia.

Ticks from mainland Australia (Victoria, New South Wales and Queensland) and Tasmania, identified morphologically as either Ixodes holocyclus or Ixodes cornuatus, were compared genetically using 24 enzyme loci. The results showed that ticks from three localities in Victoria were genetically similar to I. cornuatus in Tasmania, but both groups had fixed genetic differences at >45% of loci compared with other ticks on the mainland. In addition, there were fixed genetic differences at 0-60% of loci among I. holocyclus from different localities on the mainland. Ixodes holocyclus samples could be divided into four distinct clusters (with fixed genetic differences >15%), three of which were represented by one or two specimens. Nonetheless, these electrophoretic data suggest that I. holocyclus represents a species complex. The results also showed that the morphological criteria used to identify specimens were not always accurate because several specimens had been mis-identified morphologically. Despite limitations with the morphological identification, this study has demonstrated that I. cornuatus can be distinguished from the I. holocyclus species complex using six enzyme loci, providing the foundation for a re-examination of morphological characteristics. The present study has shown that I. cornuatus and the I. holocyclus complexes have a greater distribution than previously reported, with both occurring in sympatry at Cape Patterson, on the southern coastline of Victoria.

Alleles↗
PubMed2000

Risks of intravenous administration of hypotonic fluids for pediatric patients in ED and prehospital settings: let's remove the handle from the pump.

Fluid resuscitation of infants and children is a common management problem in prehospital and emergency department care. We present two cases of children who received 5% dextrose in water as the initial resuscitation fluid. Bolus administration of hypotonic fluid contributed to fatal outcomes in these cases. Recommendations are made for eliminating hypotonic fluids as stock items in both the prehospital and emergency department settings.

Brain Edema↗
PubMed2000

Expression of mRNAs encoding for two different olfactory receptors in a subset of olfactory receptor neurons.

Evidence has accumulated to support a model for odorant detection in which individual olfactory receptor neurons (ORNs) express one of a large family of G protein-coupled receptor proteins that are activated by a small number of closely related volatile chemicals. However, the issue of whether an individual ORN expresses one or multiple types of receptor proteins has yet to be definitively addressed. Physiological data indicate that some individual ORNs can be activated by odorants differing substantially in structure and/or perceived quality, suggesting multiple receptors or one nonspecific receptor per cell. In contrast, molecular biological studies favor a scheme with a single, fairly selective receptor per cell. The present studies directly assessed whether individual rat ORNs can express multiple receptors using single-cell PCR techniques with degenerate primers designed to amplify a wide variety of receptor sequences. We found that whereas only a single OR sequence was obtained from most ORNs examined, one ORN produced two distinct receptor sequences that represented different receptor gene families. Double-label in situ hybridization studies indicated that a subset of ORNs co-express two distinct receptor mRNAs. A laminar segregation analysis of the cell nuclei of ORNs labeled with the two OR mRNA probes showed that for one probe, the histogram of the distribution of the cell nuclei along the depth of the epithelium was bimodal, with one peak overlapping the (unimodal) histogram for the other probe. These results are consistent with co-expression of two OR mRNAs in a population of single ORNs.

Amino Acid Sequence↗
PubMed2000

A model that reproduces syndromes associated with human multiple myeloma in nonirradiated SCID mice.

A human myeloma line was used to create a model of human multiple myeloma in vivo that would reproduce the pathophysiology of the disease, including the cachexia associated with cancer. Unirradiated severe combined immunodeficient (SCID) mice were used as surrogate hosts for in vivo experiments that allowed the effects of autocrine (human) verus paracrine (murine) cytokines on the development of myeloma to be studied. Serum levels of human paraprotein increased over time and with the number of cells transplanted. Transplanted mice developed major syndromes, cachexia and paralysis (due to invasion of bones by myeloma cells), associated with multiple myeloma. Analyses of serum samples obtained from transplanted mice revealed that when the mice were terminal, total serum protein decreased on average by 20%, whereas serum triglycerides decreased on average by 50%. These data indicate the mice were cachectic, which was confirmed by necropsy. The mice had low but measurable levels of both human and murine interleukin (IL)-6, soluble IL-6 receptor, and murine IL-10 in their sera. The presence of these cytokines and the IL-6 receptor in sera are also characteristics of human myeloma in patients. Since human cells do not respond to murine IL-6, it was possible to demonstrate clearly the importance of autocrine IL-6 in establishing myeloma in situ. By reproducing both the hallmarks of a cancer as well as the accompanying paraneoplastic syndromes, this model should be useful in designing more effective therapies for both the primary cancer as well as the accompanying secondary diseases.

Animals↗
PubMed2000

Coxsackievirus expression of the murine secretory protein interleukin-4 induces increased synthesis of immunoglobulin G1 in mice.

We cloned the sequence encoding murine interleukin-4 (mIL-4), including the secretory signal, into the genome of CVB3/0, an artificially attenuated strain of coxsackievirus B3, at the junction of the capsid protein 1D and the viral protease 2Apro. Two strains of chimeric CVB3 were constructed using, in one case, identical sequences to encode 2Apro cleavage sites (CVB3/0-mIL4/47) on either side of the inserted coding sequence and, in the other case, nonidentical sequences that varied at the nucleotide level without changing the amino acid sequences (CVB3-PL2-mIL4/46). Transfection of HeLa cells yielded progeny viruses that replicated with rates similar to that of the parental CVB3/0 strain, although yields of mIL-4-expressing strains were approximately 10-fold lower than those of the parental virus. Western blot analysis of viral proteins isolated from HeLa cells inoculated with either strain of chimeric virus demonstrated that the chimeric viruses synthesized capsid protein 1D at approximately twofold-higher levels than the parental virus. mIL-4 protein was detected by enzyme-linked immunosorbent assay (ELISA) in HeLa cells inoculated with either strain of chimeric virus. Lysates of HeLa cells inoculated with either chimeric virus induced the proliferation of the mIL-4-requiring murine MC-9 cell line, demonstrating biological activity of the CVB3-expressed mIL-4. Reverse transcription (RT)-PCR analysis of viral RNA derived from sequential passaging of CVB3/0-mIL4/47 in HeLa cells demonstrated deletion of the mIL-4 coding sequence occurring by the fourth passage, while similar analysis of CVB3-PL2-mIL4/46 RNA demonstrated detection of the mIL-4 coding sequence in the virus population through 10 generations in HeLa cells. mIL-4 protein levels determined by ELISA were consistent with the stability and loss data determined by RT-PCR analysis of the passaged viral genomes. Studies of insert stability of CVB3-PL2-mIL4/46 during replication in mice showed the presence of the viral mIL-4 insert in pancreas, heart, and liver at 14 days postinfection. Comparison of the murine antibody responses to CVB3-PL2-mIL4/46 and the parental CVB3/0 strain demonstrated an increased level of CVB3-binding serum immunoglobulin G1 in mice inoculated with CVB3-PL2-mIL4/46.

Amino Acid Sequence↗
PubMed2000

Relationship between tumor location and relapse in 6,781 women with early invasive breast cancer.

PURPOSE: To explore the independent prognostic impact of medial hemisphere tumor location in early breast cancer. PATIENTS AND METHODS: A comprehensive database was used to review patients referred to the British Columbia Cancer Agency from 1989 to 1995 with early breast cancer. Patients were grouped according to relapse risk (high or nonhigh) and adjuvant systemic therapy received. Multiple regression analysis was used to determine whether the significance of primary tumor location (medial v lateral hemisphere) was independent of known prognostic factors and treatment. RESULTS: In the adjuvant systemic therapy groups, medial location was associated with a 50% excess risk of systemic relapse and breast cancer death compared with lateral location. Five-year systemic disease-free survival rates were 66.3% and 74.2% for high-risk medial and lateral lesions, respectively (P <.005). Corresponding 5-year disease-specific survival rates were 75.7% and 80.8%, respectively (P <.03). No significant differences were observed between medial and lateral location for low-risk disease regardless of adjuvant therapy or for high-risk disease with no adjuvant therapy. Local recurrence rates were similar for all risk and therapy groups. CONCLUSION: The two-fold risk of relapse and breast cancer death associated with high-risk medial breast tumors may be due to occult spread to internal mammary nodes (IMNs). Enhanced local control, such as with irradiation of the IMN chain, may be one way to reduce the excess risk. Ongoing randomized controlled trials may provide prospective answers to the question of the optimal volume of radiotherapy.

Adolescent↗
PubMed2000

Evaluation of a sexuality education program for young adolescents in Jamaica.

Despite their increasing numbers, few of the sexuality education and pregnancy prevention programs in developing countries have been evaluated. This study, conducted in 1995-1997, assesses the impact of a school-based sexuality education program, the Grade 7 Project, on 945 Jamaican seventh graders (aged 11-14) and their initiation of sexual activity and use of contraception at first intercourse, as well as the knowledge and attitudes that influence their behaviors. Using a quasi-experimental design, the study measured the effects of the Grade 7 Project when the nine-month intervention was completed (short term) and one year after that (long term). Multivariate logistic regression analysis indicated that the project had no effect on initiation of sexual activity, but it had a positive short-term impact on use of contraception at first intercourse (P = .08); adolescents in the intervention group were more than twice as likely to use contraception. The project also had a positive short-term influence on several aspects of the adolescents' knowledge of and attitudes about sexuality and pregnancy. The modest impact of the Grade 7 Project is encouraging, as school-based sexuality education programs of limited duration rarely have a long-term impact. Moreover, competing socioeconomic and cultural forces in Jamaica encourage early sexuality and parenthood among adolescents. The use of more participatory teaching methods and smaller class sizes might strengthen the Grade 7 Project and enhance its impact.

Adolescent↗
PubMed2000

Acquisition of arbitrary conditional discriminations by young normally developing children.

Three experiments investigated conditions designed to facilitate acquisition of arbitrary conditional discriminations in 3- to 6-year-old normally developing children. In Experiment 1, 6 subjects failed to master the arbitrary match-to-sample task under conditions of differential reinforcement alone, but 7 subjects did so when instructions or instructions and sample naming were added. In Experiment 2, sample naming introduced in a blocked-trial arrangement resulted in acquisition, but only when the sample name was a nonsense syllable provided by the experimenter (5 of 7 subjects) and not when the sample name was generated by the subject (0 of 5 subjects). Experiment 3 demonstrated the effectiveness of a training sequence involving thematically related stimuli as an intermediate step facilitating the transition from identity to novel arbitrary relations. The difficulties in mastering arbitrary conditional discriminations shown here imply that further analyses with young children will be particularly important in efforts to investigate the development of theoretically important stimulus relations.

Child↗
PubMed2000

Derivation and pilot assessment of a health promotion program for Mandarin-speaking Chinese older adults.

As the percentage of older adults of diverse ethnicities increases in the United States, the call for culturally sensitive health care service strategies that target the special needs of older people grows. The present report describes methods used to adapt a health care program so that it would better meet the needs of a group of well, older Mandarin-speaking Chinese residents of Los Angeles. The specific qualitative research procedures that we used to adapt the treatment program are described, along with the particular adaptations that emerged. Additionally, outcomes from a randomized pilot experiment are presented that are consistent with the notion that the adapted program was effective in reducing health-related declines among older Mandarin-speaking men and women. The overall outcome of this project is in agreement with other reports in the health care literature that address the importance of providing culturally sensitive health care service for elders.

Aged↗
PubMed2000

Good test--retest reliability for standard and advanced false-belief tasks across a wide range of abilities.

Although tests of young children's understanding of mind have had a remarkable impact upon developmental and clinical psychological research over the past 20 years, very little is known about their reliability. Indeed, the only existing study of test-retest reliability suggests unacceptably poor results for first-order false-belief tasks (Mayes, Klin, Tercyak, Cicchetti, & Cohen, 1996), although this may in part reflect the nonstandard (video-based) procedures adopted by these authors. The present study had four major aims. The first was to re-examine the reliability of false-belief tasks, using more standard (puppet and storybook) procedures. The second was to assess whether the test-retest reliability of false-belief task performance is equivalent for children of contrasting ability levels. The third aim was to explore whether adopting an aggregate approach improves the reliability with which children's early mental-state awareness can be measured. The fourth aim was to examine for the first time the test-retest reliability of children's performances on more advanced theory-of-mind tasks. Our results suggest that most standard and advanced false-belief tasks do in fact show good test-retest reliability and internal consistency, with very strong test-retest correlations between aggregate scores for children of all levels of ability.

Aptitude↗
PubMed2000

Unfair treatment, neighborhood effects, and mental health in the Detroit metropolitan area.

Why do racial differences in many indicators of mental and emotional well-being show inconsistent patterns? We propose that mental and emotional well-being are influenced by aspects of the social context, including experiences of unfair treatment and the concentration of households with incomes below the poverty level, and that differential exposure to these factors influences racial differences in mental well-being. We analyze the reporting of psychological distress and life satisfaction in a multistage area probability sample of 1,139 African American and white residents of the Detroit metropolitan area aged 18 and older. Both psychological distress and life satisfaction are significantly associated with exposure to unfair treatment and with the proportion of households in the census block group that were below the poverty level. Racial differences in psychological distress and life satisfaction were eliminated or reversed once differentials in the percent of households living below the poverty line and exposure to unfair treatment were accounted for. These findings contribute to a growing body of evidence that "race" effects operate through multiple pathways that include race-based residential segregation and its attendant economic disinvestment at the community level, and interpersonal experiences of unfair treatment.

Adolescent↗
PubMed2000

Heterogeneous recognition of beta 2-glycoprotein I by antibodies from antiphospholipid syndrome patients.

Beta 2-glycoprotein I plays a pivotal role in the binding of antiphospholipid antibodies to phospholipid in patients with antiphospholipid syndrome. In this study the nature of the epitopes on beta 2-glycoprotein I (beta2-GPI) recognised by sera from antiphospholipid syndrome (APS) patients (n = 15) was investigated and compared to rabbit polyclonal and mouse monoclonal anti-beta2-GPI antibodies. beta2-GPI was only recognised when bound to a high affinity binding support. The antigenic epitope on beta2-GPI recognised by all APS patients was also dependent on disulphide bond integrity. Digestion of beta2-GPI with elastase rapidly destroyed the epitope(s) on beta2-GPI recognised by antibodies in 91% of APS patients. The main cleavage occurred at tryptophan316-lysine317 in the fifth domain. Digestion with staphylococcal V8 protease resulted in a 50% reduction in antibody binding in 81% of patients and the cleavage sites mainly involved the first domain of the molecule. There was considerable variability in the recognition of six different species of beta2-GPI by serum from APS patients. The epitopes on beta2-GPI bound by APS sera appear conformationally determined in all patients but are quite heterogeneous in the regions of beta2-GPI that are recognised.

Adsorption↗
PubMed1999

Who Shall Lead Us?

Explore the source record for details and available documents.

Journal Article↗