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Biomedical subjects

J C Owens

Publications and source records attributed to J C Owens.

At least 19 recordsLinked to original sources

Evidence that the Lore-1 region specifies ethanol-induced activation in addition to sedative/hypnotic sensitivity to ethanol.

BACKGROUND: Low-dose ethanol-induced activation (LDA) and initial sensitivity to alcohol are both predictors of alcohol abuse in human populations. Our hypothesis is that one or more genes specifying hypnotic sensitivity also specify LDA. We tested this hypothesis by using congenic mice derived from the inbred long-sleep (ILS) and inbred short-sleep (ISS) strains, which carry an ILS region introgressed onto an ISS background. METHODS: LDA was assessed by assigning mice randomly to receive one of five doses of ethanol ranging from 1.2 to 2.4 g/kg. On day 1, animals were injected with saline and placed in a brightly lit activity monitor for 30 min, after which they were returned to their home cages. On day 2, mice were injected with ethanol (20% w/v), their activity was monitored for a 30-min period, and LDA was determined by subtracting day 1 activity. The blood ethanol concentration of each animal was then assessed at 30 min by retro-orbital collection of 25 microl of blood. RESULTS: Ethanol had a significant effect on the activity of ISS mice, but ILS mice showed no activation at any dose, similar to the activities of the outbred lines. All three congenic strains were activated at several doses. Lore-2 and Lore-5 were not ILS-like (less active than ISS) at any dose. In contrast, ISS.ILS-Lore-1 congenics (carrying an ILS-derived Lore-1 allele on the ISS background) were significantly less activated than the ISS controls at 1.8 and 2.4 g/kg of ethanol. CONCLUSIONS: The Lore-2 and Lore-5 congenic regions do not affect LDA. In contrast, the Lore-1 congenic region carries one or more genes specifying both initial hypnotic sensitivity to ethanol and LDA.

Aging↗

Cell cycle control of Cdc7p kinase activity through regulation of Dbf4p stability.

In Saccharomyces cerevisiae, the heteromeric kinase complex Cdc7p-Dbf4p plays a pivotal role at replication origins in triggering the initiation of DNA replication during the S phase. We have assayed the kinase activity of endogenous levels of Cdc7p kinase by using a likely physiological target, Mcm2p, as a substrate. Using this assay, we have confirmed that Cdc7p kinase activity fluctuates during the cell cycle; it is low in the G1 phase, rises as cells enter the S phase, and remains high until cells complete mitosis. These changes in kinase activity cannot be accounted for by changes in the levels of the catalytic subunit Cdc7p, as these levels are constant during the cell cycle. However, the fluctuations in kinase activity do correlate with levels of the regulatory subunit Dbf4p. The regulation of Dbf4p levels can be attributed in part to increased degradation of the protein in G1 cells. This G1-phase instability is cdc16 dependent, suggesting a role of the anaphase-promoting complex in the turnover of Dbf4p. Overexpression of Dbf4p in the G1 phase can partially overcome this elevated turnover and lead to an increase in Cdc7p kinase activity. Thus, the regulation of Dbf4p levels through the control of Dbf4p degradation has an important role in the regulation of Cdc7p kinase activity during the cell cycle.

Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome↗

CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication.

The initiation of DNA replication in Saccharomyces cerevisiae requires the protein product of the CDC45 gene. We report that although Cdc45p is present at essentially constant levels throughout the cell cycle, it completes its initiation function in late G1, after START and prior to DNA synthesis. Shortly after mitosis, cells prepare for initiation by assembling prereplicative complexes at their replication origins. These complexes are then triggered at the onset of S phase to commence DNA replication. Cells defective for CDC45 are incapable of activating the complexes to initiate DNA replication. In addition, Cdc45p and Cdc7p/Dbf4p, a kinase implicated in the G1/S phase transition, are dependent on one another for function. These data indicate that CDC45 functions in late G1 phase in concert with CDC7/DBF4 to trigger initiation at replication origins after the assembly of the prereplicative complexes.

Carrier Proteins↗

Treatment of adenocarcinoma of the stomach with resection, intraoperative radiotherapy, and adjuvant external beam radiation: a phase II study from Radiation Therapy Oncology Group 85-04.

BACKGROUND: Fewer than 10% of patients presenting with adenocarcinoma of the stomach in the United States can expect to be cured. These discouraging results have led to trials of various adjuvant therapies. Some studies suggest a role for radiation in improving regional control. Radiation doses, however, are limited by the tolerance of abdominal organs. METHODS: Between 1985 and 1989, the Radiation Therapy Oncology Group conducted a phase II study to determine the feasibility of using intraoperative radiotherapy (IORT) in the treatment of adenocarcinoma of the stomach. Forty-three patients were entered into the study. Patients underwent maximal surgical resection (subtotal or total gastrectomy and regional node dissection) and IORT doses of 12.5-16.5 Gy were delivered in 27 patients. Adjuvant external beam radiation was given to 23 of the 27 patients with total doses ranging from 24 to 50 Gy. RESULTS: Two-year actuarial survival in the 27 patients receiving IORT was 47% and median survival was 19.3 months. Disease-free survival was 27%. Fifteen percent failed locally only, 26% with distant metastases only and 22% with both. Acute postoperative complications occurred in 14% with one fatality. Severe late complications occurred in 7% with one fatality. CONCLUSIONS: Intraoperative radiotherapy combined with surgical resection and postoperative radiotherapy appears to be feasible without excessive morbidity in a multiinstitutional study. Its ultimate value requires further study.

Adenocarcinoma↗

Mutational analysis of the DNA-binding domain of yeast heat shock transcription factor.

Both randomized oligonucleotide cassette mutagenesis and site-directed mutagenesis have been used in combination with a yeast genetic screen to identify critical residues in the DNA-binding domain of heat shock transcription factor from Saccharomyces cerevisiae. Most of the surface residues in this highly conserved domain can be changed to alanine with no observable effect on function. Of nine critical residues identified in this screen, five are within helix alpha 3, previously designated as the probable DNA recognition helix in the crystal structure of the Kluyveromyces lactis protein. The other four residues may be involved in DNA-binding or protein-protein interactions.

Alanine↗

A phase I/II study of intraoperative radiotherapy in advanced unresectable or recurrent carcinoma of the rectum: a Radiation Therapy Oncology Group (RTOG) study.

The Radiation Therapy Oncology Group (RTOG) initiated a phase I/II study of intraoperative radiotherapy (IORT) in advanced or recurrent rectal cancer to assess therapeutic efficacy, toxicity, and establish quality control guidelines prior to beginning a phase III trial. From October 1985 through December 1989, 87 patients with histologically proven adenocarcinoma of the rectum or rectosigmoid with recurrent/persistent disease after surgery or those primarily inoperable were entered by 14 institutions. Of 86 evaluable patients, 42 patients received IORT either alone (n = 15) or in combination with external beam (n = 27). Local control was dependent on the amount of residual disease prior to IORT, with 2-year actuarial local control of 77% if no gross residual disease remained vs. 10% with gross residual disease (P = 0.001). For the recurrent/residual group (n = 33), this observation was also significant with a 2-year actuarial local control rate of 64% if no gross residual remained vs. 10% with gross residual disease (P = 0.004). Local control translated into an improved survival for all patients and the recurrent/residual group with 2-year actuarial survival of 88% and 89% if no gross residual disease remained vs. 48% and 45% with gross residual disease, respectively (P = .0005, 0.006). Six patients (14.6%) experienced four grade 3 and three grade 4 complications as a possible result of IORT during follow-up with a 2-year actuarial risk of major complications of 16%. We conclude that IORT is feasible within a cooperative group and can be performed with acceptable complication rates. A phase III trial to demonstrate a therapeutic advantage for IORT over external beam alone is currently in progress.

Actuarial Analysis↗

A comparison of two approaches for identifying reinforcers for persons with severe and profound disabilities.

The development of effective training programs for persons with profound mental retardation remains one of the greatest challenges for behavior analysts working in the field of developmental disabilities. One significant advancement for this population has been the reinforcer assessment procedure developed by Pace, Ivancic, Edwards, Iwata, and Page (1985), which involves repeatedly presenting a variety of stimuli to the client and then measuring approach behaviors to differentiate preferred from nonpreferred stimuli. One potential limitation of this procedure is that some clients consistently approach most or all of the stimuli on each presentation, making it difficult to differentiate among these stimuli. In this study, we used a concurrent operants paradigm to compare the Pace et al. (1985) procedure with a modified procedure wherein clients were presented with two stimuli simultaneously and were given access only to the first stimulus approached. The results revealed that this forced-choice stimulus preference assessment resulted in greater differentiation among stimuli and better predicted which stimuli would result in higher levels of responding when presented contingently in a concurrent operants paradigm.

Child↗

Soft tissue sarcomas of the hand and foot.

A retrospective study was made of 82 soft tissue sarcomas of the hand and foot. Prognosis was related to histopathologic grade of malignancy and success or failure of local tumor control. After treatment with curative intent, low-grade tumors gave a 5-year survival rate of 90%, compared to 63% for high-grade tumors. Simple excision or limited amputation of the digit, hand, or foot yielded a 5-year survival rate of 68% (15/22) and a local recurrence rate of 32%. Amputation below the elbow or knee or higher resulted in a similar survival of 68% (19/28) but no local recurrences. All patients who developed local recurrences died, except for two with low-grade tumors and one patient lost to follow-up. These observations indicate the need for systemic chemotherapy to prevent death from metastasis, and for effective local tumor control. Conventional radiation therapy may be difficult to apply at these sites. Innovative local treatment approaches to preserve limb function without jeopardizing tumor control merit study.

Adolescent↗

Phase II study of etoposide (VP-16) in the treatment of advanced head and neck cancer.

Eighteen patients with advanced and heavily pretreated squamous cell carcinoma of the head and neck were treated with etoposide (VP-16). Of 16 patients evaluable for response, two (13%) achieved partial response lasting 3 to 4 months, and five (31%) achieved stable disease status lasting 2 to 7 months. One patient achieved a partial response in regional lymph nodes and the primary site, while a second patient achieved a partial response of a regional lymph node recurrence. Toxicity was significant but acceptable, consisting mainly of leukopenia and alopecia. Thrombocytopenia and mild nausea were also seen. VP-16 demonstrated modest activity in this disease and might be considered for further trials.

Alopecia↗

Continuing education for the rural physician.

A two-day continuing education course in emergency care was presented in small communities of Colorado and Wyoming to 349 rural physicians. Eighty percent of the physicians in those areas participated, indicating the interest of rural practitioners in updating their training if they can do so in their own communities. Continuity of care in the communities was provided by university residents covering local hospitals and clinics. The cost was comparable with other forms of continuing education; there was no tuition fee. The success of the program suggests that the special problems of providing education in rural areas require special solutions. Courses must be designed to reach all rural physicians to satisfy the increasing demand for continuing medical education.

Colorado↗

Ovicidal levels of 2.45 GHz electromagnetic energy for the southern corn rootworm.

Eggs of southern corn rootworm (Diabrotica undecimpunctata howardi Barber) were subjected to electromagnetic energy at 2.45 GHz in slotted waveguide applicators to determine ovicidal threshold levels. Ovicidal levels at different intensities and exposure times are presented. Infrared measurements of temperature changes and estimates of the heating produced at the mical.

Coleoptera↗