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J Donegan

Publications and source records attributed to J Donegan.

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Variability in the proliferative potential of human gliomas.

One hundred forty-three patients with gliomas of astrocytic origin (61 with glioblastomas multiforme (GM) and 82 with astrocytomas) received an intravenous infusion of bromodeoxyuridine (BUdR), 150-200 mg/m2 at the time of surgery, to label tumor cells undergoing DNA synthesis. BUdR-labeled cells were identified by the indirect immunoperoxidase method using anti-BUdR monoclonal antibodies. The percentage of BUdR-labeled cells, or BUdR labeling index (LI), was calculated by microscopic examination of selected viable areas of the tissue sections. The GMs had a median LI of 7.5%, and three quarters of these tumors had LIs greater than 5%. Highly anaplastic astrocytomas (HAAs) and moderately anaplastic astrocytomas (MoAAs) had median LIs of 2.3% and less than 1%, respectively. Among the HAAs, the LI was 1% to 5% in 56% of tumors, greater than 5% in 26%, and less than 1% in 18%. More than 60% of MoAAs had LIs less than 1%, which agrees with the slow clinical progression of this type of tumor, and the remainder had LIs of 1.4% to 9.3%. These results show that histopathologically similar tumors may have different proliferative potentials. Measuring the proliferative potential of individual gliomas is therefore crucial for predicting the prognosis more accurately and for devising more tumor-specific treatment regimens for individual patients.

Astrocytoma

CPR 1986.

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Adult

The ilvB locus of Escherichia coli K-12 is an operon encoding both subunits of acetohydroxyacid synthase I.

The ilvB locus of Escherichia coli K-12 encloses two open reading frames defining polypeptides of 60,000 and 11,200 molecular weight. The entire locus, about 2.3 kb, is co-transcribed as an operon. The molecular weights and amino acid compositions of the presumptive operon polypeptides agree with those of the large and small subunit polypeptides of acetohydroxyacid synthase (AHAS) I, for which ilvB is the structural locus. We reserve the designation ilvB for the promoter proximal (longer) cistron and designate the promoter distal cistron ilvN. The molecular weight and amino acid sequence of the ilvB polypeptide are strikingly similar to those of the I1vI (larger subunit of AHAS III) and I1vG (larger subunit of AHAS II) polypeptides. There is less size uniformity among the I1vN, I1vH (smaller subunit of AHAS III), and I1vM (smaller subunit of AHAS II) polypeptides. Nevertheless, there is significant amino acid sequence homology among the three small subunit polypeptides. Thus, all three AHAS isozymes of E. coli K-12 probably have a common evolutionary origin.

Acetolactate Synthase

Characterization of a ts mutant of BALB/3T3 cells and correction of the defect by in vitro addition of extracts from wild-type cells.

ts20 is a temperature-sensitive mutant cell line derived from BALB/3T3 cells. DNA synthesis in the mutant decreased progressively after an initial increase during the first 3 h at the restrictive temperature. RNA and protein synthesis increased for 20 h and remained at a high level for 40 h. Cells were arrested in S phase as determined by flow microfluorimetry, and DNA chain elongation was retarded as measured by fiber autoradiography. Infection with polyomavirus did not bypass the defect in cell DNA synthesis, and the mutant did not support virus DNA replication at the restrictive temperature. After shift down to the permissive temperature, cell DNA synthesis was restored whereas virus DNA synthesis was not. Analysis of virus DNA synthesized at the restrictive temperature showed that the synthesis of form I and replicative intermediate DNA decreased concurrently and that the rate of completion of virus DNA molecules remained constant with increasing time at the restrictive temperature. These studies indicated that the mutation inhibited ongoing DNA synthesis at a step early in elongation of nascent chains. The defect in virus and cell DNA synthesis was expressed in vitro. [3H]dTTP incorporation was reduced, consistent with the in vivo data. The addition of a high-salt extract prepared from wild-type 3T3 cells preferentially stimulated the incorporation of [3H]dTTP into the DNA of mutant cells at the restrictive temperature. A similar extract prepared from mutant cells was less effective and was more heat labile as incubation of it at the restrictive temperature for 1 h destroyed its ability to stimulate DNA synthesis in vitro, whereas wild-type extract was not inactivated until incubated at that temperature for 3 h.

Animals

Clinical cerebral blood flow measurement with inhaled xenon and CT.

Cerebral blood flow measurement has not yet been attempted with xenon and CT in patients. Xenon washout was studied in three patients receiving subanesthetic concentrations of xenon. Cerebral enhancement after 30%--50% inhaled xenon was demonstrated without serious side effects. Clinical cerebral blood flow measurements with xenon and CT may be feasible.

Cerebrovascular Circulation

Training in advanced cardiac life support.

The nationally recognized training and certification program in Advanced Cardiac Life Support consists of lecture material and a new concept in training and testing for the practical skills of Advanced Cardiac Life Support. The course content follows closely the concepts of advanced life support as explained in the standards on cardiopulmonary resuscitation and emergency cardiac care.

Allied Health Personnel