Expandable metal stents for the treatment of colonic obstruction: techniques and outcomes

Modulation of CD8(+) T-cell responses specific for an exogenous antigen by epitope variants would be advantageous to develop a novel means of antigen-specific immune regulation. We have analyzed CD8(+) T-cell responses to single amino acid-substituted variants of a peptide corresponding to residues 142-149 (p142-149; LAYFYPEL) of alphas1-casein, a major milk allergen, which is a dominant determinant restricted by H-2Kb. An analog peptide L142I with a substitution of Ile for Leu at the nonanchor N-terminal residue induced more IFN-gamma secretion than p142-149 from specific CD8(+) T cells. Furthermore, L142I could prime CD8(+) T cells more efficiently in vivo, and these L142I-primed cells secreted more IFN-gamma than p142-149-primed CD8(+) T cells upon stimulation with p142-149 in vitro. These findings are mainly explained by the greater ability of L142I to form stable Kb-peptide complexes. These findings indicate that appropriate analog peptides may be useful as efficient inducers of CD8(+) T cells which recognize the parent peptide and secrete IFN-gamma, a potent inhibitor of Th2-dependent events, including IgE production.     

Identification of residues in the cysteine-rich domain of Raf-1 that control Ras binding and Raf-1 activity

We have identified mutations in Raf-1 that increase binding to Ras. The mutations were identified making use of three mutant forms of Ras that have reduced Raf-1 binding (Winkler, D. G., Johnson, J. C., Cooper, J. A., and Vojtek, A. B. (1997) J. Biol. Chem. 272, 24402-24409). One mutation in Raf-1, N64L, suppresses the Ras mutant R41Q but not other Ras mutants, suggesting that this mutation structurally complements the Ras R41Q mutation. Missense substitutions of residues 143 and 144 in the Raf-1 cysteine-rich domain were isolated multiple times. These Raf-1 mutants, R143Q, R143W, and K144E, were general suppressors of three different Ras mutants and had increased interaction with non-mutant Ras. Each was slightly activated relative to wild-type Raf-1 in a transformation assay. In addition, two mutants, R143W and K144E, were active when tested for induction of germinal vesicle breakdown in Xenopus oocytes. Interestingly, all three cysteine-rich domain mutations reduced the ability of the Raf-1 N-terminal regulatory region to inhibit Xenopus oocyte germinal vesicle breakdown induced by the C-terminal catalytic region of Raf-1. We propose that a direct or indirect regulatory interaction between the N- and C-terminal regions of Raf-1 is reduced by the R143W, R143Q, and K144E mutations, thereby increasing access to the Ras-binding regions of Raf-1 and increasing Raf-1 activity.     

Long-term sweat collection using salt-impregnated pads

To facilitate a study of the pharmacokinetics of drugs dissolved in sweat, a technique was devised for collecting sweat at a steady rate over an 8-day period. Three normal subjects each wore 4 absorbent pads applied to their skin under waterproof dressings for 8 days. The absorbent pads were either plain cotton or cotton impregnated with sodium chloride crystals. Each pad (3 cm x 3 cm) was applied to an area of skin (2 cm x 2 cm) defined by an adhesive template, and was removed daily, weighed, and replaced, to determine progressive uptake of sweat. Sweat uptake by plain cotton pads reached a plateau value within 2 to 3 days and did not significantly increase thereafter; in contrast, uptake by the salt-impregnated pads continued at a steady rate for the full 8 days of the study (mean rate 0.79 mg/cm2/hr, SD = 0.16, N = 6). This effect may be related to an osmotic gradient across the skin, but the physiologic mechanisms are not completely clear. This appears to be a convenient tool for the collection of sweat over long periods at a steady rate.     

Radiographic evaluation of complications after jejunoileal bypass surgery

A retrospective analysis of 89 patients who underwent jejunoileal bypass surgery for morbid obesity disclosed 33 complications that were detected radiographically. Intestinal obstruction (10.1% of patients), cholecystitis (5.6%), renal stones (4.5%), peptic ulcer (3.4%), megacolon (6.7%), and elongation of the small intestine with hypertrophy of the mucosal folds of the jejunum (6.7%) were diagnosed solely by radiographic means.     

The response of transplants of cultured fetal mouse ovaries in kidneys of ovariectomized adult mice

Whole ovaries from 16-day fetal mice were cultured for 6 to 20 days and then transplanted to the kidneys of ovariectomized adult mice where they remained for one to four weeks. After three weeks in the host's kidneys, many follicles developed within the transplants and became vesiculated. Many of the oocytes within these follicles had formed the first metaphase spindle of meiosis and several had completed the first polar body. Host mice bearing transplants that contained vesiculated follicles showed uterine stimulation and keratinization of their vaginae. However, ovaries that had been in culture for more than ten days before transplantation showed a limited response to the gonadotropins and never matured sufficiently to stimulate the host's reproductive tract. No ovulations occurred in any of the transplants.