Cultural factors related to the peer review of teaching

Since 1994, the American Association for Higher Education Peer Review of Teaching Project has sought to popularize the notion that teaching is both a scholarly activity and community property to be shared with and critiqued by the larger academic community. In order to accomplish these goals, each of the three academic units at the twelve participating universities developed a pilot project that conformed to its own institutional, academic unit, and disciplinary culture. At a large Midwestern university, the academic units of mathematics, history, and nursing developed different projects. Each of these projects took account of the unit's specific culture, and this fact helps to account, in large part, for each project's success.     

A Mg(2+)-dependent endonuclease is responsible for internucleosomal DNA fragmentation in human B lymphoblastic IM9 cells

We have identified a Mg(2+)-dependent endonuclease activity from human B lymphoblastic IM9 cell lysates and nuclei using autodigestion method and DNA-native-polyacrylamide gel electrophoresis (DNA-native-PAGE) nuclease assay system. The level of the endonuclease activity in cell lysates was significantly decreased at certain stage by treatment of the cells with cycloheximide. However, the enzyme activity consistently remained for over 12 hours in the isolated nuclei of the apoptotic IM9 cells. The Mg(2+)-dependent endonuclease isolated from the nuclei by native-PAGE elution was able to catalyze the conversion of supercoiled plasmid DNA into linear form. This particular endonuclease activity was not detected in cycloheximide treated-U937 cells. Several lines of experimental evidence suggest that the Mg(2+)-dependent endonuclease localized in the nucleus may be responsible for the DNA fragmentation of apoptotic IM9 cells.     

Association of glyceraldehyde-3-phosphate dehydrogenase expression with cell motility and metastatic potential of rat prostatic adenocarcinoma

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression is increased in Dunning R-3327 rat prostatic adenocarcinoma cell lines relative to normal rat ventral prostate tissue. GAPDH expression closely correlates with cell motility of Dunning prostate cancer cell lines and accurately distinguishes cell lines with high metastatic potential from those with low metastatic potential. Increased GAPDH expression in the cancer cell lines is not simply related to increased growth rate, since rapidly proliferating normal prostate tissue did not exhibit elevated GAPDH expression.     

Risk factors associated with mucositis in cancer patients receiving 5-fluorouracil

Oral mucositis is a dose-limiting toxicity of 5-fluorouracil (5-FU). This prospective cohort study investigated factors associated with mucositis in patients receiving 5-FU for cancer of the digestive tract. Sixty-three patients (mean age 65 years) completed self-administered questionnaires and had interviews, oral examinations and unstimulated whole salivary flow measurements at baseline and follow-up appointments. The duration of follow-up was 2 months. Predictor variables included sociodemographic data, body surface area, diabetes, smoking, alcohol consumption, salivary flow, oral hygiene, presence of prostheses, performance status, regimen of cytotoxic drugs, hematological data, and herpes simplex virus antibody titer. Forty-six per cent of patients developed at least one episode of oral mucositis during cytotoxic treatment. Pearson's chi-square analysis showed that mucositis was significantly associated with xerostomia at baseline, xerostomia during chemotherapy, and lower baseline neutrophil counts (P < or = 0.05). Multiple logistic regression analysis indicated that xerostomia at baseline (odds ratio, OR = 10.0), or baseline neutrophil level under 4000 cells/mm3 (OR = 3.9) were significant predictors of mucositis. Taking into account the effect of neutrophil level at baseline, xerostomia during chemotherapy (OR = 4.5) was also a significant predictor of mucositis. The results showed that xerostomia and lower baseline neutrophil levels are significantly associated with oral mucositis. These variables should be taken into consideration in the design of intervention studies to reduce the frequency and severity of mucositis. More research is required to investigate the role of saliva and neutrophils in the pathogenesis of chemotherapy-induced mucositis.     

Carcinoids of unknown origin: comparative analysis with foregut, midgut, and hindgut carcinoids

The purpose of this study was to analyze our results of surgical treatment of arthrogryposis of the elbow and to compare our tendon transfer results using range of motion (ROM) criteria versus functional use criteria. Eighteen tendon transfers for elbow flexion in 14 children with arthrogryposis with an average follow-up period of 4 years (range, 1-14 years) and 6 elbow capsulotomies with triceps lengthening in 6 children with arthrogryposis with an average follow-up period of 5 years (range, 2-9 years) were evaluated. Each child was assessed by a questionnaire regarding functional use of the upper extremity, physical examination of ROM and strength, and a videotaped activities of daily living evaluation. Tendon transfer results were classified and compared using 2 methods of evaluation: postoperative strength and ROM and effective functional use of the tendon transfer to perform activities of daily living. The 6 elbow capsulotomies improved from an average preoperative arc of 17 degrees of motion (average extension, -2 degrees; average flexion, 19 degrees) to an average final follow-up arc of 67 degrees (average extension, -25 degrees; average flexion, 92 degrees). The 18 tendon transfers evaluated by strength and ROM criteria showed 9 triceps to biceps transfers in 9 arms (7 good, 1 fair, and 1 poor), 5 pectoralis to biceps transfers in 4 arms (1 good, 3 fair, and 1 poor), and 4 latissimus dorsi to biceps transfers in 3 arms (2 good and 2 fair). Evaluation by functional use criteria gave the same result in 13 transfers and downgraded the result in 5; the downgraded results were due to resultant flexion contracture or limited functional use because the transfer was in the nondominant arm. Based on this review, optimal surgical candidates for tendon transfer are children older than 4 years, who have full passive ROM of the elbow in the dominant arm, and at least grade 4 strength of the muscle to be transferred.     

Use of digitalis glycosides to identify the mechanisms of amantadine transport by renal tubules

The mechanism(s) for uptake of organic cations by renal cortical tubules was (were) examined further. Renal cortical tubules were purified from rat kidneys by a Percoll gradient centrifugation technique. Bicarbonate buffer (Krebs-Henseleit, KHS) conditions were altered, and chemical modulators were used which affect the activity of the basolateral Na+/K+-ATPase. Renal tubule uptake of the achiral organic cation amantadine was determined. The cardiac glycosides digoxin and acetylstrophanthidin and ouabagenin did not alter amantadine uptake by either proximal or distal tubule fragments in KHS. However, ouabain inhibited proximal tubule amantadine uptake in a dose-dependent manner with lower potency than distal tubule amantadine uptake in KHS. Ouabain did not inhibit amantadine tubule uptake in phosphate buffer. However, inhibition of amantadine uptake by ouabain returned in a time-dependent manner upon addition of bicarbonate to the phosphate buffer. Low extracellular sodium or potassium did not alter amantadine uptake by proximal tubules. Hypokalemic and hypokalemic/ hyponatremic conditions decreased the inhibitory potency of ouabain for amantadine uptake by proximal tubules. For distal tubules, both hyponatremic and hypokalemic conditions, alone and together, decreased the inhibitory potency of ouabain, but did not affect amantadine uptake in the absence of ouabain. Hypochloremic conditions decreased affinity for amantadine uptake by distal, but not proximal tubules. No change in maximal transport capacity for amantadine uptake was observed under hypochloremic conditions for either tubule fragment. These studies challenge the widely accepted concept of Na+/ K+-adenosine triphosphatase activity and maintenance of the basolateral membrane potential as rate-limiting steps for the energy-dependent renal tubule uptake of organic cations. Furthermore, these studies suggest a mechanism for ouabain inhibition of organic cation renal tubule uptake that may not involve the Na+/K+-adenosine triphosphatase and may be possibly bicarbonate-dependent.     

Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma

PURPOSE: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 ((131)I). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of (131)I-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. MATERIALS AND METHODS: Twenty patients with advanced NHL entered the study a total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. (131)I-Lym-1 was given after Lym-1 and (131)I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m2 body surface area. RESULTS: Mean radiation dose to the bone marrow from body and blood (131)I was 0.34 (range, 0. 1 6 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/ MBq). Dose-limiting toxicity was grade 3 to 4 thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two doses of (131)I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71 %) of 14 entries who received at least two doses of (131)I-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of (131)I-Lym-1. CONCLUSION: (131)I-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).     

Inhibition of host RNA polymerase II-dependent transcription by vesicular stomatitis virus results from inactivation of TFIID

The present study tested the hypothesis that one or more tyrosine kinase(s) are downstream of protein kinase C (PKC) in the signal transduction pathway responsible for the cardioprotective effect of ischemic preconditioning (PC). Isolated rabbit hearts were subjected to 30 min of regional ischemia followed by 2 h of reperfusion. Infarct size was measured by triphenyltetrazolium staining and expressed as a percentage of the area at risk. Infarction in control hearts was 32.9+/-1.8%. Ischemic PC with 5-min ischemia/10-min reperfusion reduced infarct size to 11.5+/-1.5% (P<0.05). Infusion of the tyrosine kinase inhibitors, genistein (50 microM) or lavendustin A (0.5 microM), alone did not affect the level of infarction. When infused around the 5-min PC ischemia genistein failed to block protection (13.7+/-1.0%). However, when present at the onset of the 30-min ischemia both genistein and lavendustin A completely aborted protection (31.4+/-2.0 and 28.1+/-1.5%, respectively). Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 0.05 nmol) was as protective is ischemic PC (14.9+/-3.0%; P<0. 05). Similar to PC, PMA-induced protection was completely prevented by both genistein and lavendustin A. Conversely, anisomycin (50 ng/ml), an activator of MAP kinase kinases (dual tyrosine and threonine kinases), was very protective (7.5+/-1.6%; P<0.05) and this protection was still present when PKC was inhibited by 5 microM chelerythrine (12.1+/-1.6%; P<0.05). In conclusion, activation of a tyrosine kinase during the long ischemia appears to be required for cardioprotection in the rabbit heart. Furthermore, the ability of tyrosine kinase inhibitors to block PMA-induced protection in conjunction with the failure of PKC inhibition to prevent anisomycin-induced protection suggests that the tyrosine kinase is downstream of PKC and that the tyrosine kinase may be a MAP kinase kinase.