Activation and detoxification of dinitropyrenes by cytosol and microsomes from Aroclor-pretreated rats in the Ames and umu assays

PURPOSE: To evaluate the efficacy of topical mitomycin C in treating conjunctival and corneal epithelial dysplasia and neoplasia. METHODS: Seven eyes of seven patients with conjunctival and corneal epithelial dysplasia and neoplasia were treated with one drop of topical mitomycin C 0.04% four times a day for 7 days in alternate weeks. The patients' charts were reviewed retrospectively. Patients with either multiple recurrences or extensive ocular surface involvement were treated. In all eyes, the diagnosis of epithelial dysplasia or neoplasia was confirmed by histopathology before the onset of therapy. Patients were examined at least every 14 days during treatment and examined at intervals after completion of treatment. RESULTS: With topical mitomycin C, six eyes of seven patients had complete clinical regression of their conjunctival and corneal epithelial dysplasia and neoplasia. One eye of one patient had partial clinical regression of conjunctival and corneal epithelial dysplasia. Follow-up after completion of topical mitomycin C therapy and excision of residual disease ranged from 2 to 16 months (mean, 9 months; SD, 4.3 months) and was without clinical sign of recurrence. Topical mitomycin C therapy was associated with transitory ocular discomfort, conjunctival injection, tearing, photophobia, and punctate epithelial keratopathy. CONCLUSION: In this small series of eyes, topical mitomycin C was effective as a treatment for conjunctival and corneal epithelial dysplasia and neoplasia.     

Effects of feeding different levels of dietary fiber through the addition of corn stover on nutrient utilization of dairy heifers precision-fed high and low concentrate diets

The objective of this experiment was to assess the effects of manipulating dietary fiber by replacing corn silage (CS) with lower quality forage as corn stover (CST) when used in high concentrate (HC) and low concentrate (LC) diets for precision-fed dairy heifers. Eight Holstein heifers (335.6 ± 7.41 kg of body weight) were randomly assigned to 2 levels of concentrate: HC (20% forage) and LC (80% forage), and to a forage type sequence [0% of forage as corn stover (CST), 100% corn silage (CS); 20% CST, 80% CS; 40% CST, 60% CS; and 60% CST, 40% CS] within concentrate level administered according to a split-plot, 4 × 4 Latin square design (21-d periods). Heifers fed HC had higher apparent total-tract dry matter digestibility (DMD). Increasing the fiber level by increasing the amount of CST in the diet resulted in a linear decrease of DMD and organic matter digestibility. Heifers fed LC diets had higher neutral detergent fiber (NDF) digestibility and tended to have lower acid detergent fiber (ADF) digestibility than those fed HC diets. Substituting CS with 20% CST resulted in the highest NDF and ADF digestibilities. Digestibility of N was not different, but N retention increased for HC and decreased quadratically for LC diets. Heifers fed HC diets decreased fecal output, and CST linearly increased these parameters. Urine volume tended to be higher for HC-fed heifers, and increasing dietary fiber through CST inclusion tended to decrease urine output. This shift in water excretion resulted in similar total manure output. Total purine derivative excretion did not differ between treatments, but interacted with CST addition, resulting in a linear increase in microbial protein flow to the duodenum in HC-fed heifers and in a linear decrease in LC diets as CST increased. In conclusion, increasing dietary fiber through CST decreased DMD and organic matter digestibility linearly, whereas NDF and ADF digestibility were maximized when 20% CST was added to HC and LC diets. Microbial protein synthesis increased and decreased linearly with CST addition in HC and LC diets, respectively. Retention of N increased and decreased quadratically with CST addition in HC and LC diets, respectively. Total manure excretion was not different between HC or LC diets.     

A retrospective study of changes in physical symptoms and body image after reduction mammaplasty

Reduction mammaplasty is performed typically to alleviate the painful physical symptoms of macromastia. Women who suffer from macromastia also frequently present to the plastic surgeon with heightened body image dissatisfaction and maladaptive behavioral changes in response to their breast size. Numerous investigations have demonstrated improvement in physical symptoms after breast reduction surgery. Studies have also suggested that psychological improvement occurs postoperatively; however, they have not used well-validated, standardized psychological measures. The present study is a retrospective analysis of the physical and psychological status of women who underwent reduction mammaplasty. One hundred ten patients who underwent a reduction mammaplasty between 1982 and 1996 were mailed a packet of questionnaires designed to assess current physical symptoms and body image. Sixty-one of the 110 patients (55 percent) responded. The vast majority reported substantial improvement or elimination of neck, back, shoulder, and breast pain, grooving from bra straps, poor posture, skin irritation, and social embarrassment. In addition, they reported significantly less dissatisfaction with their breasts as compared with a sample of breast reduction patients assessed preoperatively. Symptom relief and improved body image occurred independently of preoperative body weight, as we found few significant differences between obese and non-obese women concerning the resolution of physical symptoms or improvement in body image. Results provide further evidence of the efficacy of reduction mammaplasty not only for relief of physical symptoms but also for alleviation of body image dissatisfaction.     

Novel antitumor 2-cyanoaziridine-1-carboxamides

A set of 20 2-cyanoaziridine-1-carboxamides was synthesized from 2-cyanoaziridine and appropriate isocyanates. These compounds were active against a variety of solid and hematological tumor cells in culture, including strains resistant to doxorubicin and mitoxantrone. Their potencies in these assays correlated with the lipophilicity of substituents. The N-phenyl derivative was more potent and equally effective to imexon, a cyclized 2-cyanoaziridine-1-carboxamide of clinical interest, against cloned fresh human tumors.     

Directed mutagenesis studies of the metal binding site at the subunit interface of Escherichia coli inorganic pyrophosphatase

Recent crystallographic studies on Escherichia coli inorganic pyrophosphatase (E-PPase) have identified three Mg2+ ions/enzyme hexamer in water-filled cavities formed by Asn24, Ala25, and Asp26 at the trimer-trimer interface (Kankare, J., Salminen, T., Lahti, R., Cooperman, B., Baykov, A. A., and Goldman, A. (1996) Biochemistry 35, 4670-4677). Here we show that D26S and D26N substitutions decrease the stoichiometry of tight Mg2+ binding to E-PPase by approximately 0.5 mol/mol monomer and increase hexamer stability in acidic medium. Mg2+ markedly decelerates the dissociation of enzyme hexamer into trimers at pH 5.0 and accelerates hexamer formation from trimers at pH 7.2 with wild type E-PPase and the N24D variant, in contrast to the D26S and D26N variants, when little or no effect is seen. The catalytic parameters describing the dependences of enzyme activity on substrate and Mg2+ concentrations are of the same magnitude for wild type E-PPase and the three variants. The affinity of the intertrimer site for Mg2+ at pH 7.2 is intermediate between those of two Mg2+ binding sites found in the E-PPase active site. It is concluded that the metal ion binding site found at the trimer-trimer interface of E-PPase is a high affinity site whose occupancy by Mg2+ greatly stabilizes the enzyme hexamer but has little effect on catalysis.