Transluminal excimer laser angioplasty of experimentally-induced atheromatous plaque: morphologic changes and importance of proliferation of smooth muscle cells

To determine the time-course of morphological changes after excimer laser treatment of atherosclerotic carotid arteries, laser angioplasty was performed in 34 rabbits after production of an intimal plaque (13 +/- 6 cell layers, 30 +/- 9% stenosis) using electrical stimulations. The animals were sacrificed 3, 7, 14, 21, 28, and 42 days after laser treatment. A total or subtotal thrombotic occlusion was found in four cases. No perforation was observed, but in 10 animals histological examination evidenced a partial ablation of the medial layer with signs of local thrombus formation and local reduction of SMC in the media. In five animals a stenosis of more than 50% of luminal reduction was due to intimal proliferation of smooth muscle cells (SMC), as determined by a monoclonal antibody against alpha-actin. After the initial ablation, a continuous increase of intimal cell layers was found, from 7 +/- 6 cell layers (19 +/- 9% stenosis) at 7 days, to 28 +/- 5 cell layers (45 +/- 18% stenosis) at 28 days following excimer laser angioplasty (p less than 0.01). After 42 days no additional increase of intimal thickening occurred. Our data suggest that incidence and morphology is comparable to the proliferative response of SMC following conventional balloon angioplasty.     

The effects of menstrual phase and nicotine abstinence on nicotine intake and on biochemical and subjective measures in women smokers: a A preliminary report

Nicotine intake, menstrual and smoking withdrawal symptomatology, and baseline cortisol and MHPG were assessed in nine women smokers under conditions of ad lib smoking and overnight abstinence in three menstrual phases (early follicular, mid-to-late follicular, and late luteal). A trend towards higher nicotine intake p <0.100 was observed in the mid-to-late follicular phase. Although me menstrual symptomatology was not significantly elevated during the smoking abstinence condition overall, abstinence appeared to prevent the normal reduction in symptomatology during the mid-to-late follicular phase that occurred under conditions of ad lib smoking. Menstrual and withdrawal symptoms were highly correlated, and both were most pronounced during the late luteal/abstinence condition. The smoking-specific item “craving” reflected this pattern, though in attenuated form, suggesting that the observed exacerbation of withdrawal symptomatology was not simply due to generalized dysphoria, as queried in both instruments. MHPG was significantly elevated in the late luteal phase, whereas cortisol was significantly higher during ad lib smoking than during abstinence and tended to be highest in the mid-to-late follicular phase. Further investigation will be needed to determine the functional significance of these findings for understanding and treating smoking in women.     

Simultaneous occurrence of acute myelogenous leukemia and seminoma of the testis

Summary Simultaneous tumors are rarely encountered during the course of acute leukemias. We report on a case of seminoma of the testis that occurred during the evolution of acute myelogenous leukemia. To our knowledge, this stimultaneous association has not previously been described, but a causal relationship was not apparent in the present case. The likelihood of a common carcinogenesis existed, but direct exposure to carcinogens could not be established. Although the results of a physical examination and echography were normal at the time of diagnosis, we cannot exclude the presence of microscopic cancer of the testis. Since the dissemination pattern of seminoma is usually slower than that observed in this case and the disease remains limited to the lymph nodes for long periods following dissemination, the rapid development of the present case might have been attributable to the immunosuppression and the scrotal sepsis that occurred during the induction therapy. Immunosuppression might have stimulated the progression of a primary microscopic seminoma and the development of metastasis, whereas the scrotal sepsis and inflammation might have favored the occurrence of metastasis through bypass of the lymphatic barrier.     

Low sodium haemodialysis reduces interdialytic fluid consumption but paradoxically increases post-dialysis thirst.

BACKGROUND: Interdialytic weight gain (IDWG) can be reduced by lowering the dialysate sodium concentration ([Na]) in haemodialysis patients. It has been assumed that this is because thirst is reduced, although this has been difficult to prove. We compared thirst patterns in stable haemodialysis patients with high and low IDWG using a novel technique and compared the effect of low sodium dialysis (LSD) with normal sodium dialysis (NSD). METHODS: Eight patients with initial high IDWG and seven with low IDWG completed hourly visual analogue ratings of thirst using a modified palmtop computer during the dialysis day and the interdialytic day. The dialysate [Na] was progressively reduced by up to 5 mmol/l over five treatments. Dialysis continued at the lowest attained [Na] for 2 weeks and the measurements were repeated. The dialysate [Na] then returned to baseline and the process was repeated. RESULTS: Baseline interdialytic day mean thirst was higher than the dialysis day mean for the high IDWG group (49.9+/-14.0 vs 36.2+/-16.6) and higher than the low weight gain group (49.9+/-14.0 vs 34.1+/-14.6). This trend persisted on LSD, but there was a pronounced increase in post-dialysis thirst scores for both groups (high IDWG: 46+/-13 vs 30+/-21; low IDWG: 48+/-24 vs 33+/-18). The high IDWG group demonstrated lower IDWG during LSD than NSD (2.23+/-0.98 vs 2.86+/-0.38 kg; P<0.05). CONCLUSIONS: Our results indicate that patients with high IDWG experience more intense feelings of thirst on the interdialytic day. LSD reduces their IDWG, but paradoxically increases thirst in the immediate post-dialysis period.     

Role of 4-1BB in Allograft Rejection Mediated by CD8+ T Cells

Blockade of traditional costimulatory molecules fails to inhibit rejection in many models where CD8+ T cells are sufficient to mediate rejection. This observation demonstrates that in many settings CD8+ T cells are not dependent upon CD28 or CD154 signals to mediate rejection. 4-1BB (CD137) has been shown to be an important regulatory molecule for CD8+ T cells in a variety of nontransplant models. Here we show that blocking the 4-1BB pathway significantly inhibited rejection of intestinal allografts by CD8+ but not CD4+ T cells. This effect was associated with significantly decreased expression of the genes encoding TNFalpha and secondary lymphoid chemokine (SLC) within the spleens of recipient mice. Disruption of the 4-1BB pathway also impaired the priming of alloantigen-specific CD8+ T cells and the accumulation of recipient dendritic cells within the spleen. These data directly demonstrate an important role for 4-1BB in allograft rejection; particularly rejection mediated by CD8+ T cells. Our data suggest that in addition to providing a direct costimulatory signal to T cells, the 4-1BB pathway may regulate other important steps in the immune response such as the migration of T cells and dendritic cells.     

Structure of the BoLA-DRB3 gene and promoter.

The cattle major histocompatibility complex (MHC) class II DR gene product is a heterodimer encoded by the BoLA-DRA and -DRB3 genes. Several groups have isolated cDNA and genomic clones for these genes, but their full genomic organization has not been described. We used a combination of long-range polymerase chain reaction (PCR), cloning and sequencing to define the organization of the DRB3 gene on existing genomic clones and in genomic DNA. We estimate the size of the coding region to be 11.4 kbp. Sequencing of full-length PCR clones from two different haplotypes confirmed that they carried complete DRB3 genes and allowed the design of probes and primers to isolate and characterize the DRB3 promoter and 3' end. Fragments carrying the 5' end of the DRB3 gene and its promoter were identified on bacterial artificial chromosome (BAC) clones carrying the BoLA-DR genes. A 10-kbp promoter fragment was subcloned from one clone and a 1.7-kbp region including exon 1 and the promoter was sequenced. A 3-kbp fragment encoding exons 4-6 and the entire 3' untranslated region of the DRB3 gene was isolated from lambda clone A1 and sequenced. This provides us with improved characterization of the DRB3*0101 and DRB3*2002 alleles, and also subcloned 5' and 3' flanking regions of the polymorphic DRB3 gene for use in functional studies.