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Biomedical subjects

J Jackson

Publications and source records attributed to J Jackson.

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

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Journal Article↗
PubMed1999

In vitro expansion of a multipotent population of human neural progenitor cells.

The isolation and expansion of human neural progenitor cells have important potential clinical applications, because these cells may be used as graft material in cell therapies to regenerate tissue and/or function in patients with central nervous system (CNS) disorders. This paper describes a continuously dividing multipotent population of progenitor cells in the human embryonic forebrain that can be propagated in vitro. These cells can be maintained and expanded using a serum-free defined medium containing basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), and epidermal growth factor (EGF). Using these three factors, the cell cultures expand and remain multipotent for at least 1 year in vitro. This period of expansion results in a 10(7)-fold increase of this heterogeneous population of cells. Upon differentiation, they form neurons, astrocytes, and oligodendrocytes, the three main phenotypes in the CNS. Moreover, GABA-immunoreactive and tyrosine hydroxylase-immunoreactive neurons can be identified. These results demonstrate the feasibility of long-term in vitro expansion of human neural progenitor cells. The advantages of such a population of neural precursors for allogeneic transplantation include the ability to provide an expandable, well-characterized, defined cell source which can form specific neuronal or glial subtypes.

Brain↗
PubMed1999

Impact of a new cervical pap smear screening guideline on member perceptions and comfort levels.

BACKGROUND: An evaluation was conducted to assess patient perceptions and comfort levels with a new triennial Pap smear screening guideline. METHODS: A random sample of women ages 20-69 (N = 673) was selected among members of three provider groups within a large health maintenance organization and mailed a survey. Questions pertained to Pap smear history and perceptions of the new guideline. RESULTS: The overall response rate was 63%. Over one-half of respondents had no recollection of being informed about the change in recommendation. Fourteen percent of subjects responded positively to the change, 16% were neutral, 20% were skeptical, and 50% made negative comments. Women significantly more likely to be negative or skeptical about the new guide line were those who reported more frequent prior Pap smears (P < 0.0001), those reporting a history of abnormal Pap smear (P < 0.01), and more educated women (P < 0.05). No statistical differences were found for those reporting a recent abnormal result, or based on provider group, age, or recollection of being informed. CONCLUSIONS: Regardless of patient knowledge and intellectual understanding of screening intervals, this new guideline raises patient concern about preventive care. More must be done to educate women regarding the change in recommended screening frequency and the reasons for it.

Adult↗
PubMed1999

Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT2A receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats.

5-Hydroxytryptamine2A (5-HT2A) receptor kinetics was studied in cerebral cortex and brain stem of streptozotocin (STZ) induced diabetic rats. Scatchard analysis with [3H] (+/-) 2,3dimethoxyphenyl-1-[2-(4-piperidine)-methanol] ([3H]MDL100907) in cerebral cortex showed no significant change in maximal binding (Bmax) in diabetic rats compared to controls. Dissociation constant (Kd) of diabetic rats showed a significant decrease (p < 0.05) in cerebral cortex, which was reversed to normal by insulin treatment. Competition studies of [3H]MDL100907 binding in cerebral cortex with ketanserin showed the appearance of an additional low affinity site for 5-HT2A receptors in diabetic state, which was reversed to control pattern by insulin treatment. In brain stem, scatchard analysis showed a significant increase (p < 0.05) in Bmax accompanied by a significant increase (p < 0.05) in Kd. Competition analysis in brain stem also showed a shift in affinity towards a low affinity State for 5-HT2A receptors. All these parameters were reversed to control level by insulin treatment. These results show that in cerebral cortex there is an increase in affinity of 5-HT2A receptors without any change in its number and in the case of brain stem there is an increase in number of 5HT2A receptors accompanied by a decrease in its affinity during diabetes. Thus, from the results we suggest that the increase in affinity of 5-HT2A receptors in cerebral cortex and upregulation of 5-HT2A receptors in brain stem may lead to altered neuronal function in diabetes.

Animals↗
PubMed1999

T cell proliferation, MHC class II restriction and cytokine products of gliadin-stimulated peripheral blood mononuclear cells (PBMC).

The immune response of PBMC to gliadin was investigated in patients with coeliac disease (CoD) by examining proliferation, MHC restriction and cytokine production. Gliadin induced low levels of proliferation in 63% of eight untreated patients, 32% of 28 treated patients and 35% of 31 healthy control subjects. In MHC restriction studies, the proliferative response to gliadin was inhibited (range 47-98% inhibition) in the presence of a MoAb to HLA-DR in each of three coeliac and three control donors studied. Using flow cytometry, increased expression of activation markers (HLA-DR and IL-2R) was demonstrated on gliadin-stimulated T cells from four of nine coeliac patients and three of seven healthy control donors. Cytokines were studied in culture supernatants using ELISA. Gliadin was a potent inducer of IL-6 and IL-10 in 100% of coeliac patients and controls, whereas IL-4 was not produced in either subject group. Gliadin induced IL-2 production in 40% of untreated patients, 42% of treated patients and 35% of healthy control donors. Interferon-gamma (IFN-gamma) in gliadin-stimulated cultures was found only in coeliac patients, observed in 33% of untreated patients and 25% of treated patients. Spontaneous secretion of both IL-2 and IFN-gamma was found more frequently in patients with untreated disease (87% of cases versus 21% of controls for IFN-gamma and 40% versus 0% for IL-2). These results suggest, as manifest by IFN-gamma production, that gliadin stimulates a Th1/Th0-like response in coeliac patients and a Th0-like response in healthy controls.

Adolescent↗