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Biomedical subjects

K Campbell

Publications and source records attributed to K Campbell.

At least 109 records · Page 6Linked to original sources
PubMed1995

Regional incorporation and site-specific differentiation of striatal precursors transplanted to the embryonic forebrain ventricle.

The developmental potential of neural progenitors derived from the E13.5-E14 lateral or medial ganglionic eminences (LGE and MGE, respectively) or the E12 ventral mesencephalon (VM) was examined in cross-species transplantation model. After injection into the E15 rat forebrain ventricle, mouse LGE progenitors (unlike those of the MGE or VM) were consistently integrated into the host striatum, expressing neurochemical phenotypes and axonal projections characteristic of striatal projection neurons. Additionally, both LGE and MGE precursors displayed widespread incorporation into distinct forebrain and midbrain structures, whereas the more caudally derived VM cells were largely confined to midbrain structures. These results suggest that many LGE precursors are positionally specified for striatal incorporation, while a portion also possess greater potential reflected in more widespread integration following intraventricular injection.

Animals↗
PubMed1995

Role of alterations in Ca(2+)-associated signaling pathways in the immunotoxicity of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmental pollutants that are known to be carcinogenic and immunotoxic. The effects of PAHs on the immune system of various animals and models have been studied for at least 30 yr. Despite these efforts, the mechanism or mechanisms by which PAHs exert their effects on the immune system are still largely unknown. During recent years, the molecular events associated with lymphocyte activation and receptor-mediated signaling have become increasingly clear. Substantial progress has been made in understanding the molecular and cellular bases for toxicant-induced immune cell injury. Understanding mechanisms of drug or chemical effects on the immune system is an important area of research in the field of immunotoxicology, and indeed in all fields of toxicology. Mechanistic toxicology plays an important role in risk assessment and extrapolation of potential human health effects. In this review, we have summarized recent evidence that has examined the effects of PAHs on the immune system of animals and humans. In particular, we have focused on the effects of PAHs on cell signaling in lymphoid cells and have examined the hypothesis that PAHs alter lymphocyte activation via calcium-dependent mechanisms. Previously published reports are discussed, and new data obtained with murine B cells and cell lines are presented demonstrating the relationship between alterations in intracellular calcium and immune dysregulation. These data demonstrate a strong association between PAH-induced alterations in B- and T-lymphocyte activation and changes in calcium homeostasis.

Animals↗
PubMed1995

Integration of physical, breakpoint and genetic maps of chromosome 22. Localization of 587 yeast artificial chromosomes with 238 mapped markers.

Detailed physical maps of the human genome are important resources for the identification and isolation of disease genes and for studying the structure and function of the genome. We used data from STS content mapping of YACs and natural and induced chromosomal breakpoints to anchor contigs of overlapping yeast artificial chromosome (YAC) clones spanning extensive regions of human chromosome 22. The STSs were assigned to specific regions (bins) on the chromosome using cell lines from a somatic hybrid mapping panel defining a maximum of 25 intervals. YAC libraries were screened by PCR amplification of hierarchical pools of yeast DNA with 238 markers, and a total of 587 YAC clones were identified. These YACs were assembled into contigs based upon their shared STS content using a simulated annealing algorithm. Fifteen contigs, containing between 2 and 74 STSs were assembled, and ordered along the chromosome based upon the cytogenetic breakpoint, meiotic and PFG maps. Additional singleton YACs were assigned to unique chromosomal bins. These ordered YAC contigs will be useful for identifying disease genes and chromosomal breakpoints by positional cloning and will provide the foundation for higher resolution physical maps for large scale sequencing of the chromosome.

Chromosome Mapping↗
PubMed1995

Cisplatin and chronic oral etoposide as salvage therapy for advanced colorectal carcinoma.

Patients with metastatic colorectal carcinoma who have failed 5-fluorouracil-based chemotherapy have no effective second-line treatment available. Recent studies demonstrating clinical synergy between cisplatin and etoposide, and others exploring the efficacy of etoposide regimens utilizing chronic oral administration, suggested the utility of a new regimen incorporating these elements to treat refractory colorectal carcinoma. Fourteen patients were treated with weekly cisplatin and daily oral etoposide for 21 days in cycles of 28-35 days. Toxicity was significant, both hematologic and gastrointestinal in these pretreated patients. There were no objective responses, and median survival was 9.5 months. Weekly cisplatin and daily oral etoposide are poorly tolerated and ineffective in the treatment of refractory colorectal carcinoma. Further studies are needed to discover effective therapy for this disease.

Adenocarcinoma↗
PubMed1995

In vitro purging with BCR-ABL antisense oligodeoxynucleotides does not prevent haematologic reconstitution after autologous bone marrow transplantation.

We treated a patient with chronic myeloid leukaemia in accelerated phase with autologous bone marrow transplantation. Before reinfusion, cells were purged in vitro with a 26-mer phosphorothioate antisense oligodeoxynucleotide specific for the B2A2 junction. Incubation with antisense oligodeoxynucleotides produced a 24 and 41% reduction of CFU-GM and CD34+ cells, respectively. However, an in vitro test previously performed as a screening for patient inclusion in this procedure, revealed a 38 and 75% reduction of colony formation after 24-h and 168-h incubation, respectively. The patient showed bone marrow engraftment 15 days after reinfusion and haematological reconstitution after 17 and 25 days for platelets and neutrophils, respectively. Using fluorescence in situ hybridization in interphase nuclei, we demonstrated the presence of a proportion of Ph-negative cells in repeated controls after the autograft. The patient is now in unmaintained complete haematological remission 9 months after the autograft.

Antigens, CD↗
PubMed1995

CNS-derived neural progenitor cells for gene transfer of nerve growth factor to the adult rat brain: complete rescue of axotomized cholinergic neurons after transplantation into the septum.

A CNS-derived conditionally immortalized temperature-sensitive neural progenitor (CINP) cell line was used to generate NGF-secreting cells suitable for intracerebral transplantation. The cells were transduced by repeated retroviral infection, using a vector containing the mouse NGF cDNA under the control of the LTR promoter. Subcloning at the permissive temperature (33 degrees C) identified a highly NGF-secreting clone (NGF-CINP), which contained multiple copies of the transgene and released NGF at a rate of 2 ng/hr/10(5) cells in vitro, both at 33 and 37 degrees C, which was approximately 1 order of magnitude higher than what was possible to achieve in the heterogeneously infected cell cultures. After transplantation to the brain, the NGF-CINPs differentiated into cells with a predominant glia-like morphology and migrated for a distance of 1-1.5 mm from the implantation site into the surrounding host tissue, without any signs of overgrowth and tumor formation. Grafts of NGF-CINP cells implanted into the septum of adult rats with complete fimbria-fornix lesion blocked over 90% of the cholinergic cell loss in the medial septum and grafts placed in the intact striatum induced accumulation of low-affinity NGF receptor positive fibers around the implantation site. Expression of the NGF transgene in vivo was demonstrated by RT-PCR at 2 weeks after grafting. It is concluded that the immortalized neural progenitors have a number of advantageous properties that make them highly useful experimental tools for gene transfer to the adult CNS.

Animals↗
PubMed1994

Prefrontal corticostriatal afferents maintain increased enkephalin gene expression in the dopamine-denervated rat striatum.

The cortical contribution to the maintenance of preproenkephalin (PPE) and preprotachykinin (PPT) mRNA levels in the rat striatum was investigated using quantitative in situ hybridization histochemistry. The effects of knife-cut transections of the frontal cortical pole on the expression of PPE and PPT mRNA in rat striatal neurons was studied in intact striata and in striata previously denervated by a 6-hydroxydopamine (6-OHDA) lesion of the mesencephalic dopamine pathways. Lesions of the dopaminergic striatal afferents resulted in marked increases in the mRNA encoding PPE throughout the striatum, including the ventral striatum and nucleus accumbens, while the levels of PPT mRNA were considerably reduced in these structures. Knife-cut lesions of the frontal cortical pole, transecting the prefrontal corticostriatal projection at the level of the foreceps minor, displayed little or no effect on the expression of either PPE or PPT mRNA in the dopamine-intact striatum. Conversely, frontal cortical transections performed 4 weeks after the 6-OHDA lesions reversed the 6-OHDA-lesion-induced increase in PPE mRNA in the striatum as well as in the ventral striatum and nucleus accumbens. The down-regulation of PPE mRNA in the dopaminergically denervated striatum was most pronounced in the medial part, which is the area most densely innervated by the frontal cortical pole. Here, the level of PPE mRNA expression per striatal cell was similar to the intact striatum. In contrast, the cellular expression of PPE mRNA remained up-regulated in the lateral striatum, which receives more sparse innervation from the frontal cortical pole. Cortical transections did not significantly affect the 6-OHDA-lesion-induced down-regulation of PPT mRNA in any of the striatal regions analysed. The present results demonstrate that knife-cut transections of the frontal corticostriatal pathway are capable of reversing the increased striatal PPE mRNA levels, but not the decreased PPT mRNA levels, induced by a 6-OHDA lesion of the dopaminergic input. These observations suggest that in the absence of a functional striatal dopamine input, augmented glutamatergic transmission in corticostriatal afferents is necessary to maintain increased levels of PPE mRNA expression, and hence also enkephalin synthesis, in striatal projection neurons.

Animals↗
PubMed1994

Brain-derived neurotrophic factor enhances striatal neuropeptide expression in both the intact and the dopamine-depleted rat striatum.

In order to elucidate the importance of the striatal GABAergic neurones in mediating functional effects of exogenously applied brain-derived neurotrophic factor (BDNF) in the basal ganglia, we performed daily injections of BDNF or vehicle into the dopamine-depleted striatum of unilaterally 6-hydroxydopamine-lesioned rats for 1 week. In situ hybridization revealed that BDNF exacerbated the lesion-induced up-regulation of preproenkephalin (PPE) mRNA, and completely reversed the lesion-induced decrease of preprotachykinin (PPT) mRNA. In contrast, striatal levels of trkB mRNA were not significantly affected by BDNF administration. Up-regulation of PPE and PPT mRNA was also observed in unlesioned BDNF-injected animals. We conclude that exogenously applied BDNF increases neuropeptide mRNA expression in striatal neurones independently of the presence of a dopaminergic innervation.

Animals↗
PubMed1994

Personality traits are linked to crime among men and women: evidence from a birth cohort.

Is there a relationship between personality and criminal behavior? We addressed this question in a representative birth cohort of 862 male and female 18-year-olds. Personality was assessed with the Multidimensional Personality Questionnaire (MPQ). The MPQ measures 10 relatively independent personality traits and was not designed to identify offenders. Delinquency was assessed via 3 data sources: self-reports, informant reports, and official records. Variable-centered analyses revealed that MPQ scales indexing negative emotionality and behavioral constraint were consistent predictors of delinquency across the 3 data sources. Person-centered analyses revealed that youths abstaining from delinquency were uniquely characterized by low interpersonal potency. Youths involved in extensive delinquency were uniquely characterized by feelings of alienation, lack of social closeness, and risk taking. Advances in understanding criminal behavior can be made through research that places the personality-delinquency link in a developmental context.

Adolescent↗
PubMed1994

Structural barriers to the use of formal in-home services by elderly Latinos.

We examined data on elderly Latinos to identify structural barriers that influence the use of a visiting nurse, home health aide, and/or homemaker, and to investigate possible cultural influence on use. Data are from the 1988 Commonwealth Fund Commission's national survey of 2,299 Latinos age 65 and over. Logistic equations are estimated for all elderly Latinos, those with a hospitalization in the past year, and those without a hospitalization. Need factors consistently increase the odds of using services. The significance of Medicaid and poverty income demonstrates income barriers to community-based care. Living arrangements improve our models only for those with a hospitalization in the past year. Acculturation has no independent effect, although some other findings can be interpreted as cultural preferences. We conclude that a universal, public long-term care program would substantially reduce barriers faced by elderly Latinos, but that nonfinancial barriers are likely to continue.

Aged↗
PubMed1994

Effects of rate of tone-pip stimulation on the evoked K-Complex.

The effects of rate of presentation on the evoked K-Complex were examined. In different conditions, brief duration tone pips were presented every 5, 10 or 30 s. Trials were sorted into those on which a K-Complex was or was not elicited and averaged separately. The evoked K-Complex consisted of two different negative components peaking at approximately 350 and 550 ms (respectively), followed by a positive component peaking at approximately 900 ms. K-Complexes were elicited more often in Stage 2 early and 2 late than in slow-wave sleep although the differences were not significant. K-Complexes were elicited more often in the Long ISI compared to the Short and Medium ISI conditions. When a K-Complex was evoked, the amplitude of N350 and N550 was greater for the Long ISI than for the Short or Medium ISI conditions. P900 amplitude remained invariant regardless of the ISI. A micro-analysis was carried out whenever 3 consecutive occurring K-Complexes were elicited. During the Short and Medium ISI conditions, N350 and N550 following the second and third occurrence of the K-Complex were significantly attenuated compared to the first occurrence. There was no difference in N350 and N550 amplitudes among the 3 consecutive occurrences during the Long ISI condition. The decay in amplitude over consecutive occurrences of the K-Complex might be a reflection of either habituation or refractory processes.

Journal Article↗
PubMed1994

Prostacyclin production in acute, chronic, and long-term experimental portal hypertension.

BACKGROUND: Chronic portal hypertension (PHT) is characterized by a high portosystemic shunt (PSS) and increased splanchnic blood flow. It has been suggested that the splanchnic vasodilator, prostacyclin (PGI2), mediates this increased flow. We studied splanchnic PGI2 production both in normal rabbits and in three groups of rabbits after partial portal vein ligation (PVL-PHT): acute (within 30 minutes of ligation), chronic (3 weeks after ligation), and long-term (3 months after ligation) to determine whether increased splanchnic production is a mechanism for the elevated PGI2 in PHT. METHODS: Levels of 6-keto prostaglandin F1 alpha were determined by radioimmunoassay, and splanchnic hemodynamics were measured with Doppler flowmetry in four groups of rabbits: portal normotensive rabbits, and PVL-PHT rabbits 30 minutes, 3 weeks, or 3 months after partial PVL. Splanchnic PGI2 production (PGI2 PROD) was then calculated. RESULTS: Portal pressure and PSS in chronic and long-term groups were significantly elevated in all groups compared with normals (p < 0.001). Splanchnic blood flow initially fell from 84 +/- 4.8 to 37.4 +/- 7 ml/min/100 gm immediately and then rose to 144.7 +/- 9.6 ml/min/100 gm and 137 +/- 15 ml/min/100 gm at 3 weeks and 3 months after ligation, respectively. PGI2 production rose immediately after partial portal ligation from 62 +/- 10 to 164 +/- 4.1 ng/min/100 gm and remained elevated thereafter. CONCLUSIONS: The mechanism for elevated PGI2 in acute PHT is unclear, but in chronic and long-term PHT, it is probably due in part to increased splanchnic PGI2 production.

Acute Disease↗
PubMed1993

Nucleotide sequence of the gene coding for Clostridium botulinum (Clostridium argentinense) type G neurotoxin: genealogical comparison with other clostridial neurotoxins.

The neurotoxin gene from Clostridium botulinum type G was cloned as a series of overlapping DNA fragments generated using polymerase chain reaction (PCR) technology and primers designed to conserved regions of published botulinal toxin (BoNT) sequences. The 5'-end of the gene was obtained using a primer based on a conserved region of the nontoxic-nonhaemagglutinin gene lying upstream of the toxin gene. Translation of the nucleotide sequence derived from the cloned PCR fragments demonstrated that the gene encodes a protein of 1297 amino acid residues (rmm 149, 147). Comparative alignment of the determined BoNT/G sequence with those of other clostridial neurotoxins revealed highest sequence relatedness (approx. 58% amino acid identity) with BoNT/B of proteolytic and non-proteolytic C. botulinum. Tetanus toxin (TeTx) and other BoNT types revealed lower levels of relatedness with BoNT/G (approximate range 35-42% amino acid identity).

Amino Acid Sequence↗
PubMed1993

Signaling-defective mutants of the B lymphocyte antigen receptor fail to associate with Ig-alpha and Ig-beta/gamma.

The B cell receptor for antigen, the membrane immunoglobulin (mIg) molecule, is normally expressed in association with at least two other proteins, mb-1 (Ig-alpha) and B29 (Ig-beta/gamma). We have previously described a set of murine B cell clones transfected with wild-type and mutated forms of membrane-bound IgM (mIgM) that vary in their ability to transduce signals to the cell interior. Analysis of the B cell receptor complex in signaling and nonsignaling mutants of mIgM reveals complete concordance between intact signaling ability and ability of the mIgM to associate with Ig-alpha and Ig-beta/gamma. These results point to the importance of the mIgM transmembrane region in mediating binding to accessory molecules, and provide support for a role of Ig-alpha and Ig-beta/gamma that extends beyond surface expression to signal transduction in B lymphocytes.

Amino Acid Sequence↗
PubMed1993

An all age group study of the prevalence of asthma in Golden Bay.

AIMS: To determine the prevalence of asthma within the total population of a region defined by census and geographical boundaries. METHODS: Patients on the asthma register of the sole medical centre in the region of Golden Bay, during the period of six months before the March 1991 census, were compared by age and sex with the census figures for the whole population. The methods of verifying the numbers on the register are described. RESULTS: The total number of patients of all age groups under treatment for asthma was 260, giving a prevalence of asthma in the population of 4803 of 5.41% (males 5.67%, females 5.11%). In children between ages 1-14 years there were 9.21% with asthma. The prevalence, defined by percentage for each group, rises from infancy to peak in the mid teens at 10%, followed by a steady decline to the mid thirties to 3.4%, and thereafter a rather flat plateau between 3.5% and 4% into old age. CONCLUSIONS: Previous studies of the prevalence of asthma have been limited to schoolchildren. Whole population studies, within a defined region, are likely to offer more information for the planning of healthcare resources, and may give some clues to understanding the natural history of the disease.

Adolescent↗