Laser irradiation and balloon dilatation in experimental transluminal angioplasty

Percutaneous transluminal balloon angioplasty (PTA) is being currently used in patients with coronary artery disease. Laser irradiation (LI) has been effective in vaporizing atherosclerotic plaques. The purpose of this work was twofold: to compare PTA and LI techniques in the recanalization of experimental obstructive arterial lesions, and to evaluate the possibility of reducing the failures and local complications and increasing the success rate of PTA by the combined use of LI. Atherosclerotic iliac stenoses were induced in 27 rabbits; lesions were evaluated angiographically before and after intervention and were studied histologically and by electron microscopy. Argon-ion LI delivered through microlens-tip optic fibers reduced the stenotic area from 64.2 +/- 21.8% to 40.3 +/- 10.7% (n = 10, P less than .01) and PTA from 60.7 +/- 15.9% to 30.4 +/- 7.7% (n = 9, P less than .01). However, percentage reduction was higher in PTA-treated stenoses (48.4 +/- 10.1% vs 34.5 +/- 13.5%, P less than .0125). In eight more rabbits, low power LI (4.55 +/- 1.25 J) was delivered after PTA in dilated segments. Post-PTA LI further decreased stenoses (from 31.2 +/- 7.8% to 29.1 +/- 8.1%, P less than .0125); laser-irradiated segments showed diffuse carbonization of the disrupted intimal layer. The normalized transtenotic pressure gradient decreased significantly in all groups: LI reduced the gradient from .40 +/- .25 to .17 +/- .07 (P = .005); PTA from .37 +/- .14 to .11 +/- .04 (P = .001); LI after PTA from .40 +/- .16 to .12 +/- .06 (P = .001). Thus, LI is effective (less than PTA) in relieving experimental atherosclerotic stenoses and seems useful when combined with PTA.     

Treatment with para-chlorophenylalanine antagonises the emetic response and the serotonin-releasing actions of cisplatin in cancer patients.

To test the role of serotonin in chemotherapy-induced nausea and emesis, ten cancer patients were pretreated with the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA). PCPA (2 g 8 hourly for 2 or 3 days prior to cisplatin) reduced the spontaneous urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), inhibited the increase in urinary 5-HIAA induced by cisplatin and markedly attenuated the acute period of nausea and vomiting associated with the cytotoxic drug. These results indicate that gastrointestinal serotonin mediates cisplatin-induced emesis and that the amount of serotonin released by cisplatin is a major factor in determining the severity of the acute period of emesis experienced by the patient.     

Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.      

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.