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C J Anderson

Publications and source records attributed to C J Anderson.

At least 19 recordsLinked to original sources
PubMed2007

Sex steroids modulate alpha 1-adrenoceptor-stimulated Ca2+ elevation in human cultured prostatic stromal cells.

BACKGROUND: Benign prostatic hyperplasia is an age- and androgen-dependent condition of urethral compression caused by prostatic contractility and glandular enlargement. In this study we investigate whether testosterone, dihydrotestosterone and estradiol modulate the ability of human cultured prostatic stromal cells (HCPSCs) to respond to the adrenoceptor agonists, noradrenaline (30 microM) and phenylephrine (100 microM), the protein kinase C activating phorbol ester, phorbol diacetate (PDA, 10 microM), and the L-type Ca(2+) channel activator, (-)-Bay K8644 (Bay K, 10 microM) with elevations of intracellular Ca(2+) ([Ca(2+)](i)). METHODS: Cells were loaded with the Ca(2+) sensitive fluorophore, FURA-2AM (10 microM) and changes in intracellular Ca(2+) determined before and 8-12 min after ligand addition. RESULTS: Compared to steroid-free (SF) controls, the incubation of HCPSC with testosterone (30 and 300 pM) significantly increased responses to both noradrenaline and phenylephrine. Responses to Bay K were significantly reduced between 30 nM to 300 pM but responses to PDA were not greatly affected. Compared to SF the addition of estradiol (E(2), 100 pM) did not affect responses to phenylephrine. The concomitant addition of dihydrotestosterone (DHT) and E(2) (to give ratios from 1:1 to 1,000:1) elevated the responses to noradrenaline and phenylephrine at the extreme ranges. Responses to PDA and Bay K generally increased as DHT:E(2) approached unity. CONCLUSIONS: These results indicate that sex steroids modulate the activities of HCPSCs through the regulation of both receptors and signal transduction processes.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2006

Hypoxic regulation of telomerase gene expression by transcriptional and post-transcriptional mechanisms.

Basal telomerase activity is dependent on expression of the hTERT and hTR genes and upregulation of telomerase gene expression is associated with tumour development. It is therefore possible that signal transduction pathways involved in tumour development and features of the tumour environment itself may influence telomerase gene regulation. The majority of solid tumours contain regions of hypoxia and it has recently been demonstrated that hypoxia can increase telomerase activity by mechanisms that are still poorly defined. Here, we show that hypoxia induces the transcriptional activity of both hTR and hTERT gene promoters. While endogenous hTR expression is regulated at the transcriptional level, hTERT is subject to regulation by alternative splicing under hypoxic conditions, which involves a switch in the splice pattern in favour of the active variant. Furthermore, analysis of the chromatin landscape of the telomerase promoters reveals dynamic recruitment of a transcriptional complex involving the hypoxia-inducible factor-1 transcription factor, p300, RNA polymerase II and TFIIB, to both promoters during hypoxia, which traffics along and remains associated with the hTERT gene as transcription proceeds. These studies show that hTERT and hTR are subject to similar controls under hypoxia and highlight the rapid and dynamic regulation of the telomerase genes in vivo.

Alternative Splicing↗
PubMed2003

Domain-specific satisfaction in adults with pediatric-onset spinal cord injuries.

STUDY DESIGN: Interview using a structured questionnaire and standardized measures. OBJECTIVES: To determine domain-specific satisfaction levels in adults with pediatric-onset spinal cord injuries (SCI), to determine factors associated with these levels of satisfaction, and to determine the relationship of domain-specific satisfaction to overall life satisfaction in this population. SETTING: US and Canada. METHODS: The participants were adults who sustained SCI at age 18 years or younger and were 24 years of age or older at the time of interview and did not have significant head injury. In addition to providing information about themselves, including education level, employment, marital status, and community participation, they were asked to rate their level of satisfaction in seven domains: transportation in the community, educational achievement, employment opportunities, income, social/recreational opportunities, dating opportunities, and sexual experience. They also completed the satisfaction with life scale (SWLS), the Craig handicap assessment and reporting technique, the functional independence measure, and the short-form-12 perceived health scale. RESULTS: A total of 216 individuals were interviewed. The mean age at injury was 14 years and the mean age at interview was 29 years. From most satisfied to least satisfied, the domains were ranked in the following order: satisfaction with transportation in the community, educational achievement, social and recreational opportunities, sexual experiences, dating opportunities, job opportunities, and income. Age at interview, gender, and perceived health were identified in regression analyses as predictors of some of the domain-specific satisfactions, but the primary predictive factors were in the area of participation. Neither severity of neurologic impairment nor level of functional independence were predictors for any of the domains. Satisfaction in each of the domains was significantly associated with SWLS and satisfaction with dating, job opportunities, education, and income were identified as predictive factors in a regression analysis. CONCLUSIONS: Dating opportunities, job opportunities, and income are the three domains in which adults with pediatric-onset SCI are least satisfied and those domains have a significant impact on overall satisfaction.

Activities of Daily Living↗
PubMed2003

Imaging matrix metalloproteinase expression in tumors.

metastatic Matrix metalloproteinases (MMPs) are zinc-dependent secreted or transmembrane enzymes constituting a family of over 21 proteolytic members that are capable of selectively digesting a wide spectrum of both extracellular matrix (ECM) and nonmatrix proteins. MMPs play a critical role in tumor growth, angiogenesis, and metastatic processes. MMP inhibitors (MMPIs) have been extensively investigated as anti-tumor drugs, although the clinical trials thus far have been disappointing. In order to better understand the role of MMPs in cancer growth and metastasis, as well as improve the therapeutic efficacy of MMPIs, there is a need to develop new procedures to assess and/or monitor MMP activity in vivo. In addition to determining whether MMPs are present in tumors, it would be desirable to have an imaging agent that better probes other processes associated with MMP overproduction, including angiogenesis and the establishment of the growth of metastatic lesions in distant organ sites. In this paper we review the studies relating to the recent development of in vivo imaging of MMP expression. One of the purposes of this review is to discuss the current status of imaging MMP expression, which includes the types of tracers being developed and the types of imaging modalities available. Although imaging MMP expression is a relatively new area of research, the progress thus far is highly promising.

Animals↗
PubMed2002

Self-injurious behavior in children and adolescents with spinal cord injuries.

STUDY DESIGN: A case report of self-injurious behavior in four children and adolescents with spinal cord injuries (SCI). OBJECTIVES: To report a relatively unusual complication of pediatric-onset SCI, focusing on the potential role that dysesthesia may play in self-injurious behavior. SETTING: A Spinal Cord Injury Program in a Children's Hospital in Chicago that serves children from midwestern and south-central United States of America. METHOD: Case reports and literature review. RESULTS: Case reports are presented of four children or adolescents with SCI who exhibited self-injurious behavior. Two of the subjects had symptoms consistent with dysesthesia. The self-injurious behavior in these two subjects and a very young child responded to treatment with anticonvulsants. The self-injurious behavior in the fourth patient was probably the result of poor technique of using his mouth to move his hands, which responded to conservative management including education, occupational therapy and gloves. CONCLUSION: Self-injurious behavior is a relatively unusual complication of pediatric onset SCI, and may be a manifestation of dysesthesia and be responsive to treatment with anticonvulsants.

Acetates↗
PubMed2001

Toxicity and dosimetry of (177)Lu-DOTA-Y3-octreotate in a rat model.

Radiolabeled somatostatin analogs have demonstrated effectiveness for targeted radiotherapy of somatostatin receptor-positive tumors in both tumor-bearing rodent models and humans. A radionuclide of interest for cancer therapy is reactor-produced (177)Lu (t(1/2) = 6.64 d; beta(-) [100%]). The high therapeutic efficacy of the somatostatin analog (177)Lu-DOTA-Tyr(3)-octreotate (DOTA-Y3-TATE, where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was previously demonstrated in a tumor-bearing rat model (Erion et al., J. Nucl. Med. 1999;40:223P; de Jong et al., Int. J. Cancer, 2001; 92:628-633). In the current study, the toxicity and dosimetry of (177)Lu-DOTA-Y3-TATE were determined in both normal and tumor-bearing rats. Doses of (177)Lu-DOTA-Y3-TATE ranging from 0 to 123 mCi/kg were administered to rats and complete blood counts (CBCs) and blood chemistries were analyzed out to 6 weeks. No overt signs of toxicity were observed with (177)Lu-DOTA-Y3-TATE (i.e., lethargy, weight loss, scruffy coat or diarrhea) at any of the dose levels. Blood chemistries and CBCs were normal except for the white blood cell counts, which showed a dose-dependent decrease. The maximum tolerated dose was not reached at 123 mCi/kg. The biodistribution of (177)Lu-DOTA-Y3-TATE was determined in CA20948 rat pancreatic tumor-bearing rats, and the data were used to estimate human absorbed doses to normal tissues. The dose-limiting organ was determined to be the pancreas, followed by the adrenal glands. The absorbed dose to the rat CA20948 tumor was estimated to be 336 rad/mCi (91 mGy/MBq). These data demonstrate that (177)Lu-DOTA-Y3-TATE is an effective targeted radiotherapy agent at levels that show minimal toxicity in this rat model.

Animals↗
PubMed2001

Autoantibodies to the 20-kDa ribosomal proteins: identification, characterization, and new aspects on prevalence in systemic Lupus erythematosus.

Autoantibodies to the 20-kDa ribosomal proteins (L12/S10) are not well studied, especially in juveniles with systemic lupus erythematosus (SLE). Randomly selected sera from American juveniles and adults with SLE were screened for antibodies to either 20-kDa protein and P proteins and then assayed for anti-L12 and anti-S10 by immunoblot assays. In a pilot study of patients with anti-P (Cohort 1), IgG antibodies to either 20-kDa protein and, specifically, to L12 were observed in 72 and 42% of juveniles and adults, respectively. IgG antibodies to S10 were detected less frequently. In Cohort 2 patients who were chosen irrespective of autoantibody status, twice as many juveniles as adults had IgG antibodies to either 20-kDa protein. Prevalences of IgG anti-L12 and IgG anti-S10 antibodies in the juveniles were 28 and 16% and in the adults were 13 and 12%, respectively. Anti-L12 were strongly but not invariably associated with anti-P, and usually arose temporally to these antibodies. Anti-S10 activity was due to anti-Sm antibodies. We conclude that IgG anti-L12 are more prevalent in SLE than previously reported, and are responsible for the majority of activity toward the 20-kDa ribosomal proteins, especially in juveniles.

Adolescent↗
PubMed2001

A murine monoclonal anti-idiotype to anti-ribosomal P antibodies: production, characterization, and use in systemic lupus erythematosus.

Overt anti-ribosomal P (anti-P) autoantibodies are restricted to a subset of systemic lupus erythematosus (SLE) patients, and are potentially pathogenic. Covert anti-P are detected in all other individuals. An idiotype (Id) network is nonoperational in those with overt anti-P, whereas it is functional in all others. The aim of this study was to produce a murine monoclonal (mAb) anti-Id to characterize the anti-P Id network in SLE. BALB/c mice were immunized with F(ab')(2) fragments of IgG anti-P from a patient with a broadly cross-reactive Id. One mAb was chosen (mAb41) that reacted preferentially to the immunogen. This IgG1 mAb bound comparably in ELISAs to affinity-purified anti-P from 11 SLE patients with overt anti-P. This binding was partially inhibited with ribosomal P antigen. In contrast, it did not bind to affinity-purified control autoantibodies, nor to normal human IgG. mAb41 inhibited anti-P binding to ribosomal P antigen in immunoassays and on Jurkat cells. No change was detected in patients' anti-P antibodies over time when mAb41 was used in Id-specific ELISAs. We conclude that mAb41 is an anti-Id that recognizes a public idiotope within the antigen-combining site of anti-P antibodies. Thus, it is analogous to its human counterparts, and potentially, would modulate the pathogenicity of anti-P autoantibodies in vivo.

Animals↗
PubMed2001

Conjugation of monoclonal antibodies with TETA using activated esters: biological comparison of 64Cu-TETA-1A3 with 64Cu-BAT-2IT-1A3.

A simple method for conjugation of monoclonal antibodies (mAbs) with the chelating agent 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA), has been developed using commercially available reagents. This method involved activation of a single carboxyl group of TETA with N-hydroxysulfosuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide. The resulting activated ester of TETA was reacted with the anti-colorectal carcinoma mAb 1A3 at molar ratios ranging from 10:1 to 100:1 to give immunoconjugates modified with an average of 0.4 to 2.0 functional chelators per antibody molecule. The TETA-1A3 conjugate was labeled with 64Cu at specific activities as high as 15.4 microCi/microgram, and the radiolabeled mAb exhibited high in vitro serum stability and minimal loss of immunoreactivity. The biodistribution of 64Cu-labeled TETA-1A3 in hamsters bearing GW39 human colon carcinoma xenografts was compared to that of 64Cu-BAT-2IT-1A3 (BAT = 6-(p-bromoacetamidobenzyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8,11- tetraacetic acid; 2IT = 2-iminothiolane). Both conjugates showed high tumor uptake (6.60-9.05% injected dose/gram) from 24 to 48 h post-injection and generally similar blood clearance and non-target organ uptakes. Human absorbed dose estimates derived from the hamster biodistribution data showed the critical organs for both conjugates to be the large intestine and the red marrow. Our results suggest that the in vitro and in vivo performance characteristics of 64Cu-TETA-1A3 compare favorably with those of 64Cu-BAT-2IT-1A3 and that further evaluation of the diagnostic and therapeutic efficacy of 64Cu-TETA-1A3 is warranted.

Animals↗
PubMed2001

64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors.

UNLABELLED: 64Cu (half-life, 12.7 h; beta+, 0.653 MeV [17.4%]; beta-, 0.579 MeV [39%]) has shown potential as a radioisotope for PET imaging and radiotherapy. (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1-octreotide (OC) was developed for imaging somatostatin-receptor-positive tumors using conventional scintigraphy. With the advantages of PET over conventional scintigraphy, an agent for PET imaging of these tumors is desirable. Here, we show that 64Cu-TETA-OC (where TETA is 1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid) and PET can be used to detect somatostatin-receptor-positive tumors in humans. METHODS: Eight patients with a history of neuroendocrine tumors (five patients with carcinoid tumors and three patients with islet cell tumors) were imaged by conventional scintigraphy with (111)In-DTPA-OC (204-233 MBq [5.5-6.3 mCi]) and by PET imaging with 64Cu-TETA-OC (111 MBq [3 mCi]). Blood and urine samples were collected for pharmacokinetic analysis. PET images were collected at times ranging from 0 to 36 h after injection, and the absorbed doses to normal organs were determined. RESULTS: In six of the eight patients, cancerous lesions were visible by both (111)In-DTPA-OC SPECT and 64Cu-TETA-OC PET. In one patient, (111)In-DTPA-OC showed mild uptake in a lung lesion that was not detected by 64Cu-TETA-OC PET. In one patient, no tumors were detected by either agent; however, pathologic follow-up indicated that the patient had no tumors. In two patients whose tumors were visualized with (111)In-DTPA-OC and 64Cu-TETA-OC, 64Cu-TETA-OC and PET showed more lesions than (111)In-DTPA-OC. Pharmacokinetic studies showed that 64Cu-TETA-OC was rapidly cleared from the blood and that 59.2% +/- 17.6% of the injected dose was excreted in the urine. Absorbed dose measurements indicated that the bladder wall was the dose-limiting organ. CONCLUSION: The high rate of lesion detection, sensitivity, and favorable dosimetry and pharmacokinetics of 64Cu-TETA-OC indicate that it is a promising radiopharmaceutical for PET imaging of patients with neuroendocrine tumors.

Adenoma, Islet Cell↗
PubMed2000

Labeling and in vivo evaluation of novel copper(II) dioxotetraazamacrocyclic complexes.

64Cu shows promise as both a positron emission tomography imaging and radiotherapeutic radionuclide due to its half-life (T(1/2) = 12. 7 h), decay characteristics (beta(+) [19%]; beta(-) [40%]), and the capability to produce it on a large-scale with high specific activity on a biomedical cyclotron. Macrocyclic chelators are generally used as bifunctional chelators to attach Cu(II) to antibodies and peptides due to their relatively high in vitro stability. To investigate neutral Cu(II) complexes, we performed labeling experiments with six tetraazamacrocyclic ligands with different chelate ring sizes. 1,4,8,11-Tetraazacyclotetradecane-3, 9-dione (1), 1,4,8,11-tetraazacyclotetradecane-5,7-dione (2), 1,4,7, 10-tetraazacyclotridecane-11,13-dione (3), 1,4,7, 10-tetraazacyclotridecane-2,9-dione (4), 1,4,7, 10-tetraazacyclododecane-2,9-dione (5), and 1,4,7, 10-tetraazacyclotridecane-3,8-dione (6) were radiolabeled with (64)Cu. Only (64)Cu-labeled 1 readily formed a complex in high purity, and therefore was evaluated in vivo. The rapid blood, liver, and kidney clearance of (64)Cu-labeled 1 suggest that ligand 1 may be useful as a macrocyclic structure to design new bifunctional chelators for copper radionuclides in diagnostic or radiotherapeutic studies and is a potential alternative to currently used macrocyclic bifunctional chelators.

Animals↗
PubMed2000

Work experience in adolescents with spinal cord injuries.

The purpose of this study is to compare the work experiences of adolescents with spinal cord injuries (SCI) to peers without disabilities. Twenty-eight adolescents with SCI and 25 age-matched individuals without disabilities (controls) took part in the study.A structured telephone questionnaire was used to assess their experience of household chores, volunteer jobs, and paid work. The mean age at interview was 16.2 years for those with SCI and 16.0 years for control participants. There was no significant difference between the individuals with SCI and the control participants in chores or volunteer work experiences, but the individuals with SCI were significantly less likely to have paid work experience than control participants (chi2 = 13.670, p<0.001). Of the older adolescents, aged >15 to 19 years, five of 15 individuals with SCI and 16 of 16 control participants had paid work (Fisher exact test p<0.001). Of individuals with SCI, those with milder injuries and those injured at a younger age were more likely to have work experience.

Activities of Daily Living↗