A PCR-based method for uniform 13C/15N labeling of long DNA oligomers

p53 is very often mutated in human cancers. The majority of alterations are missense mutations located within the DNA-binding domain of the protein. Many reports have characterized such mutant proteins. Little is known, however, about the properties of proteins that have a missense mutation outside this domain. We investigated here the properties of 8 mutant proteins identified in human tumors as having a missense mutation in the tetramerization domain. The Arg342Gln, Glu349Asp and Gln354Arg proteins behaved like wild-type both in vitro and in cells. Two mutants, Arg342Pro and Leu344Pro, were inactive in all assays. Finally, the 3 mutant proteins Leu330His, Arg337Cys and Arg337Leu, which are inactive in vitro, showed no activity at low expression levels in cells but became active at higher expression levels. Our results reveal new phenotypes for p53 mutants and suggest that sequencing of the p53 gene from patients with tumors should be extended to exons 9 and 10 in clinical investigations.     

Interrelationships of clinical outcome, length of resection, and energy cost of walking after prosthetic knee replacement following resection of a malignant tumor of the distal aspect of the femur

An automated method for analysis of in vivo proton magnetic resonance (MR) spectra and reconstruction of metabolite distributions from MR spectroscopic imaging (MRSI) data is described. A parametric spectral model using acquisition specific, a priori information is combined with a wavelet-based, nonparametric characterization of baseline signals. For image reconstruction, the initial fit estimates were additionally modified according to a priori spatial constraints. The automated fitting procedure was applied to four different examples of MRS data obtained at 1.5 T and 4.1 T. For analysis of major metabolites at medium TE values, the method was shown to perform reliably even in the presence of large baseline signals and relatively poor signal-to-noise ratios typical of in vivo proton MRSI. Identification of additional metabolites was also demonstrated for short TE data. Automated formation of metabolite images will greatly facilitate and expand the clinical applications of MR spectroscopic imaging.     

Decision making in detecting abnormal Semmes-Weinstein monofilament thresholds in carpal tunnel syndrome

Both hands of 39 patients who had symptoms of pain and/or numbness in one or both hands were tested by two hand therapists using the full kit of Semmes-Weinstein monofilaments (SWMFs). The SWMF thresholds were obtained for the thumb, the index finger, and the long and small fingers. These thresholds were classified as normal or abnormal based on four decision rules and two criterion measures. Decision rules were based on whether SWMF 2.83 or 3.22 would be the best limit of normality, and whether the small finger should be used for within-subject comparisons. The criterion measures were the highest threshold of all three radial digits and the highest threshold of the long finger alone. Intertherapist agreement on normality was fair to moderate (kappa = 0.22-0.51), varying according to decision rules and criterion measures. Reliability was higher when the additional comparison with the small finger was omitted. High accuracy in identifying cases of carpal tunnel syndrome (CTS) was possible, but accuracy varied moderately between testers and greatly according to decision rules and criterion measurements. The best overall accuracy (81%-82% sensitivity and 57%-86% specificity) was achieved when SWMF 2.83 was used as the upper limit of normality and the small finger was used for within-subject comparison, and when data from the long finger alone were used for decision making.     

Meniscal replacement using a porous polymer prosthesis: a preliminary study in the dog

A porous polyurethane prosthesis was used to replace the lateral meniscus in the dog. After an initial ingrowth of fibrous tissue, the prostheses became filled with tissue strongly resembling normal meniscal fibrocartilage. Although less severe than seen after total meniscectomy, cartilage degeneration was frequent, possibly because tissue ingrowth in the prostheses occurred too slowly. Porous polymers can be useful for replacement of the meniscus, provided that chemical and physical properties are optimized.     

The role of diet for development of renal cell carcinoma]

Dietary risk factors for renal cell cancer were investigated in a population based case-control study of incident cases. A total of 351 cases and 340 controls matched for age and sex were interviewed about dietary habits as well as exposure to other known or suspected risk factors. An association was found between risk of renal cell cancer and energy intake, especially fats. There was no protective effect of fruits but a weak protective effect of cruceferous vegetables. The association with diet was present after adjusting for the effect of cigarette smoking, socioeconomic status and body mass index, all of which have been identified as risk factors for renal cell cancer.     

Eradication of Helicobacter pylori in patients with duodenal ulcer lowers basal and peak acid outputs to gastrin releasing peptide and pentagastrin

BACKGROUND: Patients with duodenal ulcer (DU) have high basal (BAO) and peak (PAO) acid outputs. The effect of Helicobacter pylori eradication on these variables is unclear. AIM: To discover if gastric acid hypersecretion in patients with DU is caused by H pylori. PATIENTS AND METHODS: BAO, gastrin releasing peptide (GRP), and pentagastrin stimulated PAO in 10 H pylori negative controls, and in 10 H pylori positive patients with DU was measured before and six months after H pylori eradication. H pylori status was determined by histology, culture, and by the 13C-urea breath test. After collecting a 30 minute basal aspirate, GRP 40 pmol/kg/h was infused for 45 minutes, and after a 30 minute washout, pentagastrin 6 micrograms/kg was injected intramuscularly. RESULTS: Basal and stimulated acid output (PAOGRP and PAOPg) were significantly higher in H pylori positive DU than in H pylori negative controls. Six months after H pylori eradication, basal and stimulated acid outputs were all significantly lower than before H pylori eradication. CONCLUSIONS: This study has shown that BAO, PAOGRP, and PAOPg are higher in H pylori positive DU than in H pylori negative controls. All decreased significantly six months after H pylori eradication, to fall within the range of controls. These results are compatible with a hypothesis that acid hypersecretion in duodenal ulcer disease is caused by H pylori infection.     

Effect of levamisole on pokeweed mitogen stimulation of immunoglobulin production in vitro

The effects of levamisole (LMS) on immunoglobulin (Ig) production were studied in vitro using peripheral blood lymphocytes from normal subjects stimulated with pokeweed mitogen (PWM). Cells were cultured for 9 days with varying concentrations of LMS and PWM, and immunoglobulin secretion in the supernatants was quantified by solid phase radioimmunoassay. The results showed that 1) the effect of LMS in vitro depends upon the degree of lymphocyte stimulation by PWM. When PWM stimulation is optimal, typical pharmacologic concentrations of LMS (0.5 micro/ml) decrease both IgM and IgG production by 50%. However, at lower suboptimal doses of PWM, LMS, at similar concentrations, enhances immunoglobulin production by 24% (p less than 0.01). Unstimulated lymphocytes are not affected by LMS. 2) The target cell upon which LMS acts is present among a T subpopulation that lacks the Fc receptor for aggregated rabbit IgG (T gamma -negative). We suggest that the diverse effects of LMS on autoimmune disease in vivo may depend upon both the size and degree of activation of the T gamma -negative lymphocyte pool.