Way paved for HIV settlement talks in Japan.
Explore the source record for details and available documents.
Drug Industry↗
Biomedical subjects
C Ross
Publications and source records attributed to C Ross.
Towards acceptance of organ transplantation?
Explore the source record for details and available documents.
Ethics, Medical↗
Cytokines and autoantibodies to cytokines.
Cytokines are essential components of our defense and repair systems but also potentially harmful mediators of infectious and immunoinflammatory reactions. Clinically important cytokines function systemically as pleiotropic hormones with overlapping effects on many cell types. All engage in a complex network of agonists and antagonists. Some immunoglobulin G (IgG) antibodies have been found to be potent and specific regulators of cytokines. These antibodies bind interleukin (IL-1)alpha, IL-6, IL-10, leukemia inhibitory factor (LIF), and interferon (IFN)-alpha/beta with exceptional force. They neutralize their corresponding cytokines ex vivo and perhaps in vivo, although they may also function as cytokine carriers. The biological role of autoantibodies to cytokines is not yet understood, but they may provide a level of regulation not appreciated at present. Inappropriate production/function of such antibodies could be pathogenetically involved in immunoinflammatory and other diseases. Cytokine antibodies may also contribute to the anti-inflammatory effects of human IgG therapy.
Adjuvants, Immunologic↗
High resolution structures of HIV-1 RT from four RT-inhibitor complexes.
We have determined the structures of four complexes of HIV-1 reverse transcriptase with non-nucleoside inhibitors, three fully refined at high resolution. The highest resolution structure is of the RT-nevirapine complex which has an R-factor of 0.186 and a root-mean-square bond length deviation of 0.015 A for all data to 2.2 A. The structures reveal a common mode of binding for these chemically diverse compounds. The common features of binding are largely hydrophobic interactions and arise from induced shape complementarity achieved by conformational rearrangement of the enzyme and conformational/configurational rearrangement of the compounds.
Amino Acid Sequence↗
Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors.
The structure of unliganded HIV-1 reverse transcriptase has been determined at 2.35 A resolution and refined to an R-factor of 0.219 (for all data) with good stereochemistry. The unliganded structure was produced by soaking out a weak binding non-nucleoside inhibitor, HEPT, from pregrown crystals. Comparison with the structures of four different RT and non-nucleoside inhibitor complexes reveals that only minor domain rearrangements occur, but there is a significant repositioning of a three-stranded beta-sheet in the p66 subunit (containing the catalytic aspartic acid residues 110, 185 and 186) with respect to the rest of the polymerase site. This suggests that NNIs inhibit RT by locking the polymerase active site in an inactive conformation, reminiscent of the conformation observed in the inactive p51 subunit.
Antiviral Agents↗
Immunohistochemical characterization of the cutaneous cellular infiltrate in different areas of chronic leg ulcers.
Current understanding of the immunological mechanisms involved in the pathogenesis of venous leg ulcers is insufficient. In this study the cellular composition of skin biopsies taken from the center, the edge, and 2 cm distant from the edge of venous leg ulcers was characterized quantitatively by immunohistochemical staining. In the epidermis the mean numbers of Langerhans cells (CD1a+) were four times lower at the edge of the ulcer compared to clinically intact epidermis 2 cm distant from the edge. In the dermis a statistically significant increase in the mean numbers of macrophages (CD68+) and neutrophils (NP57+) from the distant area towards the center of the ulcer was observed. No significant differences were observed in the distribution of T cells nor in the ratio of CD4+/CD8+ T-cell subsets between the different regions of the ulcer. About 30% of T lymphocytes were CD8+ in all microenvironments. The center and the edge of the ulcer were dominated by macrophages comprising 63% and 53% of the cells respectively, while T lymphocytes dominated the distant area. The area 2 cm distant from the edge was also heavily infiltrated by macrophages and neutrophils. B cells (CD22+) and NK cells (CD56+) were relatively rare in all areas, comprising less than 3% of the dermal infiltrate. In conclusion, local microenvironments each with a different cellular composition can be defined within venous leg ulcers.
Adult↗
Cytokine autoantibodies in rheumatoid arthritis.
Sera from 42 patients with rheumatoid arthritis (RA) and 40 healthy controls (HC) were examined for cytokine autoantibodies (CK-aAb) by accurate and sensitive radioimmunoassays. The prevalences of detectable CK-aAb in RA (HC) were: aAb-IL-1 alpha = 36% (38%); aAb-IL-6 = 29% (13%), p = 0.06; aAb-IL-8 = 0% (0%); aAb-IFN alpha = 12% (3%), p = 0.11. The levels of the individual CK-aAb did not correlate, and there were no correlations between CK-aAb levels and clinical or laboratory variables. CK-aAb levels remained constant in 8 RA patients tested over a period of 6 months. With regard to alterations in aAb-IL-1 alpha levels, 4/11 HC were consistently positive over 18-36 months; 2/11 converted and became highly positive. The levels of aAb-IFN alpha and aAb-IL-6, but not aAb-IL-1 alpha, tended to be increased in RA patients; aAb-IL-8 were undetectable in both RA and HC.
Adult↗
Desert Storm nursing.
Explore the source record for details and available documents.
History, 20th Century↗
What cost ritual?
Following the 1991 Nuffield Theatre Nurses Award, I was encouraged to pursue further research into the scrub procedure. My interest had originally started when looking at the possibility of installing electronic eye taps into the theatres. I reasoned that by reducing the amounts of heated water flowing unused during the scrub procedure I would be able to justify the cost of these taps. A pilot survey I undertook showed that on costs alone this was not proven. A more logical and research based approach to the subject was required. My main objectives were to ascertain costs and timings of the traditional scrub; compare the costs with other acceptable alternatives; explore 'costs' relating to wider environmental concerns; examine the effectiveness of current practice. I looked at the Government statistics for England during 1990/91. It showed an annual total of 741,393 operating sessions with a total of 3,353,797 operations performed. The total of cases in orthopaedic, opthalmic, general and gynaecological operations totalled 2,301,272 cases. These four categories were the ones I chose to research.
Clinical Nursing Research↗
Transcriptional inhibition of the bacteriophage T7 early promoter region by oligonucleotide triple helix formation.
We have identified a purine-rich triplex binding sequence overlapping a -35 transcriptional early promoter region of the bacteriophage T7. Triplex-forming oligonucleotide designed to bind this target was annealed to T7 templates and introduced into in vitro transcription systems under conditions favoring specific initiation from this promoter. These templates demonstrated significant transcriptional inhibition relative to naked genomic templates and templates mixed with non-triplex-forming oligonucleotide. It is suggested that triplex formation along this target interferes with transcriptional initiation, and this mechanism may hold potential to disrupt bacteriophage T7 early transcription in vivo.
Bacteriophage T7↗
Platelet-activating factor levels in human follicular and amniotic fluids.
Platelet-activating factor (PAF) was estimated in extracts of human follicular and amniotic fluids using a commercially available 125I-radioimmunoassay. Levels obtained before and after purification of the extracts by thin-layer chromatography were similar and PAF could be estimated with high accuracy and reproducibility over a wide dilution range. PAF levels in fluid aspirated from mature (17 mm average diameter) follicles from in vitro fertilization patients were 1005 +/- 129 fmol/ml in successful (clinical pregnancy) cycles and 949 +/- 75 fmol/ml in unsuccessful (failure of implantation) cycles. PAF levels were also similar in follicles containing eggs and those where no egg was found, and in fluid from follicular cysts characterised by low oestradiol and progesterone levels. PAF was detected in midtrimester amniotic fluid (60 +/- 20 fmol/ml). At term, PAF was low or undetectable in amniotic fluid obtained at elective caesarean section before the onset of labour, but increased to 102 +/- 28 fmol/ml in samples obtained following spontaneous labour and vaginal delivery. The data suggest that PAF may be involved in ovulation and parturition but further studies into the mechanism of action of PAF are necessary. The good performance of the radioimmunoassay and the convenience of gamma-counting are strong advantages of this method over the available bioassays, but its expense remains a drawback.
Amniotic Fluid↗
Thyroid screening tests in psychiatric inpatients.
This study reports on a retrospective evaluation of the current practice of screening for thyroid dysfunction in an adult psychiatric inpatient program. Sixty-four percent of 342 admissions were tested during their hospital stay. Although 13.7% of tests yielded abnormal values on one or more of the thyroid indices, only 0.9% resulted in a diagnosis of hypothyroidism. None of the other abnormal test results led to any specific action being taken. The present pattern of use of thyroid function screening as observed in this study does not appear optimal. Issues in the selection of thyroid screening tests, and the value of the results obtained are discussed.
Adult↗
Heterogeneity of peripheral blood monocyte populations in human immunodeficiency virus-1 seropositive patients.
Monocytes from human immunodeficiency virus (HIV) patients have an increased heterogeneity of phenotype and function. In a study of 120 HIV patients we have demonstrated that they have normal monocyte differential counts but that with progression of the disease an increasing proportion of monocytes show phenotypic and functional evidence for activation or maturation. A proportion of the monocytes are larger, with increased expression of CD11b, HLA-DR, CD45 and CD16. Concomitantly there was increased expression of TNF-alpha, high constitutive synthesis of PGE2 and high plasma IL-6 levels. This suggested that there exists a more dynamic situation of recruitment, activation and maturation of peripheral blood monocytes driven by HIV infection which results in a broader phenotypic profile.
Antigens, CD↗
Basal metabolic rate, body weight and diet in primates: an evaluation of the evidence.
The relationship between basal metabolic rate (BMR), body weight and diet is examined for primates. Contrary to the results reported in several recent works, there is no strong evidence that diet is directly linked to BMR, although a low BMR, relative to body weight, may be found in species with folivorous diets. There is some evidence that nocturnal haplorhine species have a relatively low BMR, but strepsirhines appear to have a uniformly low relative BMR regardless of their primary activity period. The evolution of BMR in primates is discussed in the light of these findings. Some predictions are made about the relative BMRs that should be found for other species whose BMR is, as yet, unknown.
Animals↗
Antisnakevenom: an over-used medication.
Fifty-five cases of snakebite were retrospectively analysed for the indications for the use of anti-snakevenom (ASV). Sixty-seven per cent of patients received treatment with ASV. Of these, 47% had features of systemic envenoming, 30% had features of local envenoming and 22% had no features of envenoming, either systemic or local. When WHO guidelines were strictly applied, it was found that in 44% of cases, ASV was used without adequate indication.
Antivenins↗
Large and rapid changes of myofibrillar total calcium during the cardiac cycle. Electron probe microanalysis of voltage-clamped guinea-pig ventricular myocytes.
At 36 degrees C and 2 mM [Ca2+]o, single guinea-pig ventricular myocytes were voltage clamped with patch electrodes. When paired pulsing had potentiated the contraction to the maximum, the cells were shock-frozen for electron probe microanalysis (EPMA). Shock-freezing was timed at the end of diastole (-80 mV) or at different times during systole (+5 mV). The same paired-pulse protocol was applied to another group of myocytes from which contraction was recorded and [Ca2+]i was estimated by microfluospectroscopy (50 microMNa-Indo-1). In potentiated cells, during the first pulse, contraction peaked within 128 +/- 25 ms after start of depolarization. [Ca2+]i peaked within 25 ms to 890 /+- 220 nM (mean +/- SEM) and fell within 100 ms to about 450 nM. sigma Camyo, the total calcium concentration in the overlapping myofilaments (A-band), was measured by EPMA in 17 potentiated myocytes. During diastole, sigma Camyo was 2.6 +/- 0.4 mmol/kg dry weight (dw), which can be converted to 0.65 mM (mmoles per liter myofibrillar space). Since [Ca2+]i was 180 nM, we estimate that 99.97% of total calcium is bound. A time-course for systolic sigma Camyo was determined by shock-freezing 13 cells at different times after start of depolarization to +5 mV. sigma Camyo was 5.5 +/- 0.3 mmol/kg dw (1.4 mM) after 15-25 ms, 4.6 +/- 0.5 mmol/kg dw (1.1 mM) after 30-45 ms, and 3.1 mmol/kg dw (0.8 mM) after 60-120 ms. The fast time-course of sigma Camyo suggests that calcium binds to and unbinds from troponin C at a fast rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Follicular monitoring and outcome of in vitro fertilization in gonadotropin-releasing hormone-agonist-treated cycles.
Previous investigations of in vitro fertilization (IVF) cycles stimulated with gonadotropins have shown that it is possible to predict IVF outcome on the basis of the pattern of estradiol (E2) production in the terminal phase of follicular growth. This analysis looked at endocrine and ultrasound parameters in the late follicular phase of 320 patients in their first cycle of IVF. All cycles were stimulated by an association of gonadotropin-releasing hormone agonists (GnRH-a) and human menopausal gonadotropins (hMG). The pregnancy rate (PR) was not related to the E2 pattern in the 5 days before ovulation induction and was 33% and 39% even when E2 values fell during hMG administration. The PR was independent of the E2 level and the number of follicles greater than 14 mm on the day of human chorionic gonadotropin administration (day 0). The incidence of multiple pregnancy increased when E2 levels were greater than 1,000 pg/mL. It is concluded that follicular phase parameters used for cycle cancellation in hMG-stimulated IVF cycles cannot be extrapolated to GnRH-a/hMG cycles.
Analysis of Variance↗
The human blastocyst: morphology and human chorionic gonadotrophin secretion in vitro.
Micromanipulation of human oocytes and embryos has provided new opportunities for both the treatment of infertility and the preimplantation diagnosis of genetic disease. It is important to determine whether manipulated embryos develop normally in vitro, as an indication of their suitability for transfer. However, at present there is little information on the development of non-manipulated embryos in vitro for comparison. We have therefore monitored morphological changes and human chorionic gonadotrophin (HCG) secretion in 36 non-manipulated human embryos, including 26 blastocysts and 10 cavitating morulae, daily from day 3 to day 14 of culture. Hatching was observed in 10 (38.5%) blastocysts and five of these adhered to the culture dish and appeared viable until day 14. The secretion of HCG was first detected on day 8, peaked at day 10 (51.11 +/- 8.7 mIU/ml) and then declined but was still detectable in four blastocysts on day 14. There was no overall difference in HCG secretion by hatched blastocysts and those which remained within the zona. However, those hatched blastocysts which showed adherence had significantly increased (P less than 0.05) HCG secretion. For individual blastocysts, the pattern of HCG secretion correlated well with the assessment of morphology. These data provide the basis for comparative studies of morphological changes and HCG secretion in manipulated embryos.
Blastocyst↗