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Biomedical subjects

C Collins

Publications and source records attributed to C Collins.

At least 37 records · Page 2Linked to original sources

Isolation of new nonsense and frameshift mutants in the immunoglobulin mu heavy-chain gene of hybridoma cells.

In order to expand the experimental material available for genetic and biochemical analyses of the natural immunoglobulin genes, we have isolated a variety of mutant mouse hybridoma cell lines. Some of these mutants have partial or complete deletions of the mu gene. Other mutants have nonsense or frameshift mutations in the exons encoding the variable and the second and third constant region domains of the mu heavy chain. When combined with earlier mutant data, this collection of genotypically and phenotypically tight mutants of known sequence spans most of the 10 kb of the mu gene, providing material for a variety of studies of genetic recombination and mRNA metabolism.

Amino Acid Sequence

Local infusion balloon angioplasty to obviate restenosis compared with conventional balloon angioplasty in an experimental model of atherosclerosis.

Balloon angioplasty is an accepted treatment for arterial obstruction; however, a substantial percentage of initially successfully treated lesions recur in the first 4 to 6 months. There is increasing interest in local treatment of lesions undergoing angioplasty to prevent restenosis, and an infusion catheter has been developed for this purpose. This study compared infusion balloon angioplasty by means of saline solution with conventional balloon angioplasty in atherosclerotic iliac arteries of 18 cholesterol-fed New Zealand white rabbits. Values for minimum stenosis diameter assessed angiographically immediately after maximum infusion balloon angioplasty (2.1 +/- 0.6 mm) and after conventional balloon angioplasty (2.3 +/- 0.3 mm, p = NS) were similar. In follow-up studies up to 5 weeks after angioplasty, the angiographic minimum stenosis diameter remained similar in the two treatment groups, but the histologically assessed intimal area was greater after infusion angioplasty (1.54 +/- 0.92 mm vs 1.02 +/- 0.75 mm in conventionally treated arteries, p = 0.0001). Infusion balloon angioplasty merits further evaluation as a treatment strategy for the simultaneous dilatation of atherosclerotic lesions with delivery of therapeutic agents to minimize restenosis.

Animals

Pacemaker function during irradiation: in vivo and in vitro effect.

With an ageing population in Australia, one would expect the probability of treating cancer patients who have a cardiac pacemaker to increase. In this paper the effect of ionizing radiation and electromagnetic interference on pacemaker function is discussed. A case of a cancer patient, with pacemaker, treated with radiotherapy without ill effect, is described. Concurrently, four pacemakers were tested in vitro with gamma radiation from a 60 Cobalt machine and no adverse effect was found. A list of precautions is recommended.

Aged

Quantification of melanin and iron content in uveal malignant melanomas and correlation with magnetic resonance image.

Eleven patients with uveal malignant melanomas (MM) were studied by magnetic resonance (MR) imaging before enucleation. The MR appearances varied, but often were different from those previously reported to be characteristic of these tumours. Using an image analyser to assess quantitatively the melanin and iron content of each tumour, a wide range of tumour melanin concentrations was found, but universally low tumour iron concentrations. These values were compared with MR appearances that were quantified and expressed as contrast to noise ratios. The correlation between T1 and T2 shortening and increasing melanin content did not reach statistical significance. There was no correlation between MR appearances and iron content. The theories postulated to explain the diverse MR appearances of uveal MMs are discussed and variations in tumour melanin content and differences in scanner strengths are suggested as the most likely explanations.

Adult

Contribution of melanogenic proteins to the heterogeneous pigmentation of human melanocytes.

Human melanocytes from individuals with different skin types, as well as from the skin of the same individual, are heterogeneous in their melanin content. This heterogeneity may be attributed to differences in the activity and expression of the three melanogenic proteins: tyrosinase and tyrosinase-related proteins 1 and 2 (gp75 and DOPAchrome tautomerase, respectively), which in turn are affected by certain regulatory factors. Established melanocyte strains that exhibited intrinsic melanogenic heterogeneity could be separated into subpopulations according to density and melanin content by Percoll density gradient centrifugation. The least melanotic subpopulation consisted of melanocytes that contained an active tyrosinase enzyme and a low amount of melanin. Tyrosinase activity and the quantities of tyrosinase enzyme, tyrosinase-related protein-1 and DOPAchrome tautomerase gradually increased with increased melanin content and Percoll density of the isolated melanocyte subpopulations. We have found a direct correlation between melanin content, tyrosinase activity and the expression of the three melanogenic proteins in melanocyte strains established from different skin types. Addition of the two epidermal cytokines, tumor necrosis factor-alpha or interleukin-1 alpha, to cultures of human melanocytes from different skin types caused decreased proliferation, tyrosinase activity and expression of tyrosinase, tyrosinase-related protein-1 and DOPAchrome tautomerase. Similar results were obtained when Percoll-derived melanocyte subpopulations were treated with tumor necrosis factor-alpha and interleukin-1 alpha. These results indicate that the variation in melanin content in human melanocytes is due to differences in the activity and expression of the melanogenic proteins, which are influenced by autocrine and paracrine factors.

Cell Separation

Penetration of the Kilkenny Health Project Education Programme.

The Kilkenny Health Project (KHP) was established in 1985 as a community-based research and demonstration programme for cardiovascular disease in County Kilkenny, Ireland, and as a pilot programme for future national initiatives. This article examines the penetration of the Project into the community, the extent of knowledge of, contact with, or participation in its activities.

Adult

Samarium-153-EDTMP biodistribution and dosimetry estimation.

Fifty-two patients were treated with single doses of 153Sm-EDTMP in a Phase I escalating dose protocol for palliation of bone pain from metastatic prostate carcinoma. Samarium-153 (T1/2 46.3 hr), maximum beta-particle energies 810 keV (20%), 710 keV (30%), 640 keV (50%), gamma photon 103 keV (28%), was complexed to the tetraphosphonate chelate, EDTMP. Five groups of patients were treated at doses of 1.0, 1.5, 2.0, 2.5, and 3.0 mCi/kg to evaluate toxicity from treatment. Patients were screened prior to treatment and followed after treatment with 99mTc-MDP bone scans. Biodistribution data on this group of patients were acquired and showed rapid uptake of 153Sm-EDTMP into bone with complete clearance of nonskeletal radiotoxicity by 6-8 hr. Also included are complete sets of dosimetry estimations on an additional seven patients who received 0.5 mCi/kg 153Sm-EDTMP Ca++ as part of a multiple dose therapy trial. Estimated radiation absorbed doses to bone surfaces averaged 25,000 mrad/mCi (6686 Gy/MBq), and urinary bladder doses averaged 3600 mrad/mCi (964 Gy/MBq).

Bone Neoplasms

Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial.

Samarium-153-ethylenediaminetetramethylene phosphoric acid (EDTMP), a bone-seeking radiopharmaceutical, was given to prostate cancer patients in a dose escalation protocol for pain palliation to determine the maximally tolerated dose. Fifty-two patients with hormone refractory prostate cancer with bony metastases were treated with doses beginning at 0.5 mCi/kg (18.5 MBq/kg), escalating in 0.5-mCi (18.5 MBq) increments to 3.0 mCi/kg (111 MBq/kg). Pain response after treatment was assessed as well as hematologic and serum chemistry parameters. Pain palliation with a mean duration of 2.6 mo was present in 74% of the patients. Toxicity was exclusively hematologic at the highest dose levels. No infectious or bleeding complications occurred, with 45 of the 52 (86%) patients demonstrating complete hematologic recovery. Patients receiving higher doses had significantly greater reductions in serum prostate specific antigen and serum prostatic acid phosphatase levels. The patients receiving greater doses also showed a trend toward improved survival.

Aged

Evaluation of routine diabetes and lipid screening after age 35 in candidates for or current users of oral contraceptives.

OBJECTIVE: To evaluate the efficacy of a diabetes and lipid screening program in women aged 35 or older who either were currently using a low-estrogen-dose oral contraceptive (OC) (0.03-0.04 ethinyl estradiol) or who desired to initiate low-dose OC therapy after using a non-OC method or following a recent pregnancy. METHODS: Healthy women with no history of abnormal glucose tolerance, hypertension, or hyperlipidemia aged 35 years and older were routinely screened for diabetes (fasting and 2-hour values after 75 g glucose) and dyslipidemia (fasting total cholesterol, high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol, and triglycerides). Three groups of women were studied: women currently using low-dose OCs (OC group), women desiring to change to OC therapy (non-OC group), and women within 3 months post-pregnancy (postpartum group). RESULTS: The three groups were similar in age, parity, body mass index (BMI), and mean arterial pressure. The mean months of contraceptive use were not different between the OC group (30.2 months; 95% confidence interval [CI] 26.6-33.8) and the non-OC group (38.4 months; 95% CI 32.0-44.8). The mean fasting serum glucose, after adjusting for age and BMI, was significantly lower in the OC group (82.4 +/- 9.4 mg/dL) than in the non-OC and postpartum groups (87.2 +/- 12.5 and 86.8 +/- 13.0 mg/dL, respectively; P = .01). After adjustments, no differences between the groups were found in the 2-hour post-glucose levels, triglycerides, or HDL or LDL cholesterol levels. The non-OC group was found to have a significantly lower total cholesterol level (188.7 +/- 32.4 mg/dL) than the OC and postpartum groups (202.7 +/- 38.1 and 204.4 +/- 41.0 mg/dL; P = .02) after adjusting for age and BMI. This association lost its significance after applying multiple range tests, maintaining an alpha error of 0.05. CONCLUSION: The absence of significant adverse metabolic markers in longer-term OC users over the age of 35, in comparison to similar-age control groups, does not support the routine use of lipid and diabetes screening before initiating or during the use of low-dose OCs.

Adult

The caregiver reaction assessment (CRA) for caregivers to persons with chronic physical and mental impairments.

The development and testing of a multidimensional instrument to assess the reactions of family members caring for elderly persons with physical impairments, Alzheimer's disease, and cancer is reported. Forty items were administered to a sample of 377 caregivers of persons with physical impairments and Alzheimer's disease. Five dimensions of caregivers' reactions were identified through exploratory factor analysis. Using confirmatory factor analysis on an independent sample (N = 377), these dimensions were tested for factorial invariance across spouse and nonspouse caregivers and between caregivers of persons with cancer and those caring for persons with Alzheimer's disease. The subscales also had a high level of factorial invariance across a three-wave panel study (N = 185). The subscales appeared consistent with first order tests of construct validity.

Aged

Squamous cell carcinoma of the cervix: HPV 16 and DNA ploidy as predictors of survival.

In this study, the hypothesis that DNA ploidy and the presence of HPV 16 and HPV 18 DNA affects survival of patients with squamous cell carcinoma of the cervix was tested. Archival paraffin blocks from biopsy and surgical specimens were obtained from 127 women diagnosed in 1977-1984. Determination of DNA ploidy was by flow cytometry and HPV 16 and HPV 18 DNA status by polymerase chain reaction with subsequent dot-blot hybridization. For each patient, age, stage, treatment modality, and 5-year survival were correlated with ploidy and HPV status. HPV 16 DNA was present in 53% of the tumors. HPV 18 was not detected in this population. HPV 16 DNA was found twice as often in Stages IB and IIA than in advanced-stage disease (III and IV). These advanced-stage tumors were more commonly aneuploid. Neither HPV status nor DNA ploidy were predictive of survival for any stage of disease or therapeutic modality.

Adult

The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain.

We have identified and sequenced cDNA clones that encode for the human beta-subunit of rod cGMP phosphodiesterase (PDEB). A single 2565-bp open reading frame that codes for an 854-amino-acid protein was identified. The human beta-subunit protein is 90% identical to the bovine beta-subunit and 91% identical to the mouse protein. Northern blot analysis indicates that the gene is expressed as an abundant 3.5-kb transcript in retina and as a rare 2.9-kb transcript in brain. The isolation of cDNAs from human brain cDNA libraries confirms the brain as a site of expression for this gene. The molecular defect underlying retinal degeneration in the rd mouse has been found to be a nonsense mutation in the beta-subunit of the mouse cGMP PDE, resulting in a truncated protein (Pittler et al., 1991b, Proc. Natl. Acad. Sci. USA. 88: 8322-8326). The molecular cloning of the cDNA encoding for the PDEB represents the first step in establishing whether this gene plays a causative role in any one of the several human hereditary retinopathies or, based on its localization to chromosome 4p 16.3, in the pathogenesis of Huntington disease.

3',5'-Cyclic-GMP Phosphodiesterases

Exclusion of DNA changes in the beta-subunit of the c-GMP phosphodiesterase gene as the cause for Huntington's disease.

To identify expressed sequences within candidate regions for the Huntington's disease (HD) gene in 4p16.3, we isolated the gene encoding the beta subunit of the human cGMP phosphodiesterase (PDEB). We formally assessed this as a candidate gene for HD based on it's expression in brain, the demonstration of linkage disequilibrium between intragenic DNA markers and HD, and the demonstration that mice with a mutation in this gene have a reduction of neurons in particular brain regions. We investigated all 22 exons of PDEB and 5'-flanking region for point mutations in 16 HD patients of different ethnic origins using single strand conformational polymorphism analysis. The underlying DNA changes found initially exclusively in HD patients were excluded as the cause for HD.

3',5'-Cyclic-GMP Phosphodiesterases

Delineation of a 50 kilobase DNA segment containing the recombination site in a sporadic case of Huntington's disease.

No detectable rearrangements involving chromosome 4p16.3 have been observed in patients with Huntington's disease (HD). New mutations for HD could involve structural alterations which might aid the localization of the defective gene. We have reinvestigated a well documented sporadic case of HD. DNA haplotyping with markers between D4S10 and the telomeric locus D4S141 reveals a recombination event in one chromosome of the sporadic HD patient. The site of recombination maps within a 50 kilobase (kb) region, about 700 kb from the 4p telomere. Based on the extremely low HD mutation rate and significantly decreased recombination in the distal region of 4p, we hypothesize a direct link between the site of the recombination and HD in this patient.

Adult

Surveying University of Arizona students' health.

The authors sampled more than 600 University of Arizona students to determine how student attitudes, beliefs, and practices should be considered by healthcare personnel in planning campus health education programs. The survey found that students worried more about diet, exercise, and weight than they did about more serious health problems and that, although generally positive and optimistic, the students frequently felt anxious and overwhelmed. Two thirds of the students were sexually active, 74% of those who were active used various contraceptive methods. More than three quarters of those surveyed indicated they currently drank alcoholic beverages; one quarter of the drinkers said they frequently downed three or more drinks on one occasion, and 44% of the drinkers reported driving while under the influence of alcohol.

Arizona

Radiochemical assay to measure the biofilm produced by coagulase-negative staphylococci on solid surfaces and its use to quantitate the effects of various antibacterial compounds on the formation of the biofilm.

A firmly adherent mass of slime plus organisms (biofilm) accumulates on the sides of culture tubes when some strains of coagulase-negative staphylococci are grown in a chemically-defined medium containing [14C]glucose. This mass was washed (to remove labelled medium) and then counted after adding scintillation fluid. Organisms from the liquid culture were also washed and counted to check that [14C]glucose had been utilised to label the bacteria. Nine strains were examined in this way, and the results were compared with those obtained with four older techniques for recognising slime production or adherent bacteria. The new method is quick, and has advantages of reproducibility and good discrimination between strains; there was a 15-fold difference in counts in the biofilm between slime-producing and non-producing strains respectively. With the new radiolabel assay, the effects of several antibacterial compounds on the build-up of the biofilm were investigated with four slime-producing strains. Tunicamycin, chloramphenicol and 5-fluorouracil, at levels below their minimum growth-inhibitory concentrations, each greatly diminished biofilm formation; several other drugs had less effect.

Adenosine Triphosphate