The 3'-terminal sequence of mitochondrial 13S ribosomal RNA

We have examined the 3'-terminal sequence of the "small" structural ribosomal RNA ("13S") of hamster cell mitochondria, using a procedure involving [3H]isoniazide labeling of samples subjected to sequential periodate oxidation and beta-elimination. The terminus was found to be PyUAUUAOH, which is similar, but not identical, to the corresponding terminus of eukaryotic cytoplasmic 18S rRNA.     

Kleene Algebra and Bytecode Verification

Most standard approaches to the static analysis of programs, such as the popular worklist method, are first-order methods that inductively annotate program points with abstract values. In [6] we introduced a second-order approach based on Kleene algebra. In this approach, the primary objects of interest are not the abstract data values, but the transfer functions that manipulate them. These elements form a left-handed Kleene algebra. The dataflow labeling is not achieved by inductively labeling the program with abstract values, but rather by computing the star (Kleene closure) of a matrix of transfer functions. In this paper we show how this general framework applies to the problem of Java bytecode verification. We show how to specify transfer functions arising in Java bytecode verification in such a way that the Kleene algebra operations (join, composition, star) can be computed efficiently. We also give a hybrid dataflow analysis algorithm that computes the closure of a matrix on a cutset of the control flow graph, thereby avoiding the recalculation of dataflow information when there are cycles in the graph. This method could potentially improve the performance over the standard worklist algorithm when a small cutset can be found.     

A randomized phase-II study of BB-10010 (macrophage inflammatory protein- 1alpha) in patients with advanced breast cancer receiving 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy

BB-10010 is a variant of the human form of macrophage inflammatory protein-1alpha (MIP-1alpha), which has been shown in mice to block the entry of hematopoietic stem cells into S-phase and to increase their self-renewal capacity during recovery from cytotoxic damage. Its use may constitute a novel approach for protecting the quality of the stem cell population and its capacity to regenerate after periods of cytotoxic treatment. Thirty patients with locally advanced or metastatic breast cancer were entered into the first randomized, parallel group controlled phase II study. This was designed to evaluate the potential myeloprotective effects of a 7-day regimen of BB-10010 administered to patients receiving six cycles of 5-fluorouracil (5-FU), adriamycin, and cyclophosphamide (FAC) chemotherapy. Patients were randomized, 10 receiving 100 microgram/kg BB-10010, 11 receiving 30 microgram/kg BB-10010, and nine control patients receiving no BB-10010. BB-10010 was well-tolerated in all patients with no severe adverse events related to the drug. Episodes of febrile neutropenia complicated only 4% of the treatment cycles and there was no difference in incidence between the treated and nontreated groups. Studies to assess the generation of progenitor cells in long-term bone marrow cultures were performed immediately preceding chemotherapy and at the end of six dosing cycles in 18 patients. Circulating neutrophils, platelets, CD 34(+) cells, and granulocyte/macrophage colony-forming cell (GM-CFC) levels were determined at serial time points in cycles 1, 3, and 6. The results showed similar hemoglobin and platelet kinetics in all three groups. On completion of the six treatment cycles, the average pretreatment neutrophil levels were reduced from 5.3 to 1.7 x 10(9)/L in the control patients and from 4.3 to 1.9 and 4.5 to 2.5 x 10(9)/L in the 30/100 microgram/kg BB-10010 groups, respectively. Relative to their pretreatment values, 50% of the patients receiving BB-10010 completed the treatment with neutrophil values significantly higher than any of the controls (P = .02). Mobilization of GM-CFC was enhanced by BB-10010 with an additional fivefold increase over that generated by chemotherapy alone, giving a maximal 25-fold increase over pretreatment values. Bone marrow progenitor assays before and after this standard regimen of chemotherapy indicated little long-term cumulative impairment to recovery from chemotherapy. Despite the limited cumulative damage to the bone marrow, which may have minimized the protective value of BB-10010 during this regimen of chemotherapy, better recovery of neutrophils in the later treatment cycles with BB-10010 was indicated in a number of patients.     

Arthrodesis of the shoulder for synovial osteochondromatosis

OBJECTIVES: To identify the reasons for non-compliance with fecal occultblood test in the screening programme for colorectal cancer. DESIGN AND SETTING: The people who had never participated in the screening programme for colorectal cancer served as the subjects of this study. A structured questionnaire which included the reasons for rejection was sent to each of non-compliers. They were requested to choose two major reasons which were described in a best way that why they did not participate in the programme. The frequency of the stated reasons were analysed from the viewpoint of both sex and age effects. MAIN RESULTS:A total of 439 people was identified as non-compliers, and 356 (81.1%) people completed the questionnaire. No significant difference was noted in response to the questionnaire between male and female as well as aged 40-59 and those 60-79. The most commonest reason was felt well (47.8%) in male, fear or shyness of further examination (40.2%) in female, and also felt well (48.5%) in aged 40-59, fear or shyness of further examination (40.1%) in aged 60-79. Significant differences were observed in the frequencies of felt well (p<0.01), fear or shyness of further examination (p<0. 01), busy for work (p<0.01) and fear of cancer (p<0.01) between male and female, and also felt well (p<0.01), fear or shyness of further examination (p<0.01), busy for work (p<0.01) and coexistent disease (p<0.01) between aged 40-59 and those 60-79. CONCLUSIONS: These results suggest that public education about the concept of asymptomatic illness, the benefits of early detection, the safety and painless colonoscopy, and the effective treatment should be emphasised to increase compliance with screening for fecal occult blood.     

Involvement of CD14 and complement receptors CR3 and CR4 in nuclear factor-kappaB activation and TNF production induced by lipopolysaccharide and group B streptococcal cell walls

This study was undertaken to evaluate the role of CD14 and complement receptors type 3 (CR3) and 4 (CR4) in mediating TNF release and NF-kappaB activation induced by LPS and cell wall preparations from group B streptococci type III (GBS). LPS and GBS caused TNF secretion from human monocytes in a CD14-dependent manner, and soluble CD14, LPS binding protein, or their combination potentiated both LPS- and GBS-induced activities. Blocking of either CD14 or CD18, the common beta-subunit of CR3 and CR4, decreased GBS-induced TNF release, while LPS-mediated TNF production was inhibited by anti-CD14 mAb only. Chinese hamster ovary cell transfectants (CHO) that express human CD14 (CHO/CD14) responded to both LPS and GBS with NF-kappaB translocation, which was inhibited by anti-CD14 mAb and enhanced by LPS binding protein. While LPS showed fast kinetics of NF-kappaB activation in CHO/CD14 cells, a slower NF-kappaB response was induced by GBS. LPS also activated NF-kappaB in CHO cells transfected with either human CR3 or CR4 cDNA, although responses were delayed and weaker than those of CHO/CD14 cells. In contrast to LPS, GBS failed to induce NF-kappaB in CHO/CR3 or CHO/CR4 cells. Both C3H/OuJ (Lps[n]) and C3H/HeJ (Lps[d]) mouse peritoneal macrophages responded to GBS with TNF production and NF-kappaB translocation, whereas LPS was active only in C3H/OuJ macrophages. Thus, LPS and GBS differentially involve CD14 and CR3 or CR4 for signaling NF-kappaB activation in CHO cells and TNF release in human monocytes, and engage a different set of receptors and/or intracellular signaling pathways in mouse macrophages.     

Transurethral cystotomy repair

We present a novel transurethral technique for cystotomy repair. This method can be used for immediate bladder repair following limited bladder injury and avoids the morbidity associated with laparotomy.     

Laser in situ keratomileusis: literature review of a developing technique

We reviewed papers published in peer-reviewed journals describing techniques and results of laser in situ keratomileusis (LASIK) and summarized the instruments used, nomograms, preoperative and postoperative refractions, predictability, outcome, safety, and complications. We performed a similar review of abstracts published in the abstract books of the 1996 meeting of the International Society of Refractive Surgery, the 1997 meeting of the Association for Research in Vision and Ophthalmology, and the 1997 meeting of the American Society of Cataract and Refractive Surgery. The number of LASIK and photorefractive keratectomy (PRK) patients described in the abstracts were sorted by city. Mean weighted latitudes were calculated and compared for each procedure. The mean preoperative refraction in the papers was -12.59 diopters (D), which was statistically higher than that in the abstracts, -8.71 D (P < .001), and the mean postoperative refraction, -1.10 and + 0.93 D, respectively. The mean percentage of cases within +/- 1.00 D was 67.0% in the papers and 82.5% in the abstracts. Uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 49.2% of eyes in the papers and 83.2% of those in the abstracts; a UCVA of 20/20 or better was achieved in 22.0 and 56.6%, respectively. The portion of eyes that lost two or more lines of best corrected visual was 8.0% in the papers and 0.9% in the abstracts. Complications in the papers included irregular flap (4.0%), incomplete cut (2.5%), free cap (4.9%), perforated lenticule (2.6%), short flap (3.0%), sliding flap (1.4%), interface debris (6.8%), central island (5.3%), decentration (4.7%), epithelial ingrowth (4.3%), induced astigmatism (5.1%), wrinkles (5.9%), haze (8.7%), night vision problems (14.0%), and reoperation (8.2%), Mean latitude for LASIK cases (27.00 degrees +/- 13.73 [SD] was significantly lower than that for PRK cases (42.85 +/- 11.7 degrees). Visual outcomes of LASIK surgery show significant improvements when recent abstracts are compared with published papers. This may reflect continued improvement in the surgical techniques, surgeons' skills, and visual outcomes.     

Obstructive sleep apnea due to endogenous testosterone production in a woman

Quantitative buffy coat (QBC) analysis has been reported to have a high degree of methodical sensitivity in the detection of human filariasis. This study was conducted to evaluate its usefulness in the diagnosis of filariasis using a Dirofilaria immitis/dog model. By necropsy of 244 stray dogs, 40.6% of the animals were found to harbor 1-58 worms of D. immitis (mean 6.5 +/- 8.4 worms/infected dog). The QBC analysis and thick blood smear (TBS) method detected microfilaremia in 31.6% and 21.3% of these dogs, respectively. The results of these two methods were highly correlated with the presence of bisexual worms in the dogs. The QBC analysis was more sensitive (55% versus 39%) and efficient (79% versus 72%) than the conventional TBS method. However, accurate speciation of the microfilariae was impossible using the QBC analysis. Although this technique is more sensitive, simpler, and less time-consuming and does not require as much skill or experience in comparison with the conventional TBS method, the failure in speciation of the parasites may limit its usefulness.     

Gene therapy strategies for AIDS-related malignancies

AIDS-related malignancies (ARM) include AIDS-defining cancers such as Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical carcinoma. In addition, certain other malignancies are also increased with human immunodeficiency virus (HIV) infection. New antiretroviral agents and better prophylaxis and treatment of HIV-related opportunistic infections are prolonging the lives of HIV-infected individuals. There will thus likely be a continued rise in the incidence and prevalence of ARM in the long term, even if effective antiretroviral and other AIDS-related therapies reduce their appearance in the short term. There are presently no curative regimens for the common ARM, with the possible exception of some lymphomas. Survival is shortened by most, and treatment is often toxic and poorly tolerated. Gene therapies may thus offer a useful adjunct to conventional treatment strategies for selected ARM. Although some gene therapy strategies may work well in the HIV setting, the chronic viral infection, immunodeficient status of the host, the tendency for HIV-infected individuals to have altered drug metabolism and an increased rate of adverse drug reactions will likely present special challenges. This review summarizes the state-of-the-art in the fledgling field of gene therapy for ARM, and explores areas for future research.