Biomedical subjects
Publications and source records attributed to A M Clark.
An ethanolic extract of the aerial parts of Mitracarpus scaber demonstrated good antimicrobial activity. Bioassay directed fractionation of this extract led to the isolation of benz[g]isoquinoline-5,10-dione (1) as an active component. Compound 1 showed significant in vitro inhibitory activity against the AIDS-related pathogens.
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The aim of this study was to assess the effect of an acute bout of high-intensity intermittent exercise on saliva IgA concentration and alpha-amylase activity, since this type of training is commonly incorporated into the training programmes of endurance athletes and games players. Eight well-trained male games players took part in the study. They reported to the laboratory after an overnight fast and performed a 60-min cycle exercise task consisting of twenty 1-min periods at 100% VO2max, each separated by 2 min recovery at 30% VO2max. Unstimulated whole saliva was collected over a 5-min period into pre-weighed tubes and analysed for total protein, saliva IgA and alpha-amylase. The saliva flow rate ranged from 0.08 to 1.40 ml x min(-1) at rest and was not significantly affected by the exercise. The performance of the intermittent exercise bout did not affect the saliva IgA concentration, but caused a five-fold increase in alpha-amylase activity (P<0.01 compared with pre-exercise) and a three-fold increase in total protein concentration (P<0.01). These returned to pre-exercise values within 2.5 h post-exercise. It has been suggested that IgA concentration should be expressed as the ratio to total protein concentration, to correct for any concentrating effect due to evaporative loss of saliva water when breathing through the mouth (as in strenuous exercise). The present study clearly demonstrates that this is not appropriate, since there is an increase in salivary protein secretion rate immediately after exercise (571+/-77 microg x min(-1) compared with 218+/-71 microg x min(-1) pre-exercise; P<0.05). The increased saliva alpha-amylase activity after exercise may improve the protective effect of saliva, since this enzyme is known to inhibit bacterial attachment to oral surfaces. The saliva alpha-amylase secretion rate was lower immediately pre-exercise than at any other instant, which may have been due to anticipatory psychological stress, although the subjects were all familiar with interval exercise. This emphasizes the need for true resting non-stressed control conditions in future studies of the effects of exercise on saliva constituents.
We have characterized three cDNAs from a gene family encoding lipid transfer proteins, LTP, from Arabidopsis thaliana (Wassilewskija). In addition to the already characterized Ltp1, our analysis includes Ltp2 and Ltp3, two sequences previously known as expressed sequence tags (EST) only. The deduced amino acid sequences of the three cDNAs share 56 to 57% identity and show unique tissue- and cell-specific expression. Genes Ltp1 and LTp2 are located within approximately 1.4 kb of each other in tandem orientation. RNA hydridizations showed that all three LTP are expressed in flowering meristems, flowers and developing seeds. Ltp1 is expressed in leaves in addition. Ltp3, though not Ltp2, is also expressed in a short segment of the stem close to the flowering meristem. In contrast to the epidermis-specific Ltp1, both Ltp2 and Ltp3 are not restricted to the epidermis, but are also expressed in sub-epidermal layers of the organs in which they are found. In the upper stem segment, Ltp3 is predominantly cortical. It appears that the expression of these three cDNAs is sufficient to account for the formation of LTP in all meristematic and expanding cells of the aboveground plant. Evolutionary analysis allows the conclusion that each Ltp belongs to a different sub-family of genes. Additionally, parsimony analysis provides evidence that several copies of Ltp genes already existed in ancestors of the Brassicaceae family.
The utilization of microbes as models for mammalian metabolism of xenobiotics has been well established since the concept was first introduced by Smith and Rosazza in the early seventies. The core assumption of this concept rests on the fact that fungi are eukaryotic organisms that possess metabolizing enzyme systems similar to those present in mammalian systems. Hence, the outcome of xenobiotic metabolism in both systems is expected to be similar, if not identical, and, thus, fungi can be used to predict the outcome of mammalian metabolism of various xenobiotics, including drugs. Utilizing microbial models offers a number of advantages over the use of animals in metabolism studies, mainly reduction in use of animals, ease of setup and manipulation, higher yield and diversity of metabolite production, and lower cost of production. In a continuation to our contribution to this field, this review will outline the results of studies that were conducted over the last seven years to emphasize the similarities between the microbial and mammalian metabolic pathways of xenobiotics through the endorsement of the concept of microbial models of mammalian metabolism .
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Glutamine is an essential substrate for the proper functioning of cells of the immune system. Falls in plasma glutamine concentration after exercise may have deleterious consequences for immune cell function and render the individual more susceptible to infection. The purpose of the present study was to examine changes in plasma glutamine concentration (measured using a validated enzymatic spectrophotometric method) following an acute bout of intermittent high-intensity exercise. Eight well-trained male games players took part in the study. Subjects reported to the laboratory following an overnight fast and performed a 1-h cycle exercise task consisting of 20 1-min periods at 100% maximal O2 consumption (VO2max) each separated by 2 min of recovery at 30% VO2max. Venous blood samples were taken before exercise and at 5 min, 1 h, 2.5 h, 5 h and 24 h post-exercise. Glutamine was measured by enzymatic spectrophotometric determination of the ammonia concentration before and after treatment of the plasma with glutaminase (EC 3.5.1.2). Plasma glutamine concentration did not fall in the immediate post-exercise period [pre-exercise 681 (23) microM compared with 663 (46) microM at 5 min post-exercise, mean (SEM)], but fell to 572 (35) microM at 5 h post-exercise (P < 0.05 compared with pre-exercise). Plasma lactate concentration rose to 8.8 (1.0) mM at the end of exercise and fell to 1.8 (0.4) mM at 1 h post-exercise, but plasma concentrations of free fatty acids and beta-hydroxybutyrate both rose substantially in the post-exercise period (to 240% and 400% of pre-exercise levels, respectively). The circulating leucocyte count increased significantly during exercise (P < 0.01), continued to increase in the hours following exercise and peaked at 2.5 h post-exercise (mainly due to a neutrophilia). The fall in the plasma glutamine concentration at 5 h post-exercise could be due to increased renal uptake of glutamine, which generally occurs in conditions of metabolic acidosis or due to a greater removal of glutamine from the plasma resulting from the elevated circulating leucocyte count.
Ninety-two plants used in the traditional pharmacopoeia of the Pech and neighboring Mestizo peoples of central Honduras are reported. The results of in vitro antimicrobial screens showed that 19 of the extracts from medicinal plants revealed signs of antifungal activity while 22 demonstrated a measurable inhibitory effect on one or more bacterial cultures. Bioassay-guided fractionation of extracts from Mikania micrantha, Neurolaena lobata and Piper aduncum produced weak to moderately active isolates. The broad spectrum of activity of the extracts helps to explain the widespread use of these plants for wound healing and other applications.
Critiques of logical positivism form the foundation for a significant number of nursing research papers, with the philosophy being inappropriately deemed synonymous with empirical method. Frequently, proposing an alternative method to those identified with the quantitative paradigm, these critiques are based on a poor foundation. This paper highlights an alternative philosophy to positivism which can also underpin empirical inquiry, that of post-positivism. Post-positivism is contrasted with positivism, which is presented as an outmoded and rejected philosophy which should cease to significantly shape inquiry. Though some acknowledgement of post-positivism has occurred in the nursing literature, this has yet to permeate into mainstream nursing research. Many still base their arguments on a positivistic view of science. Through achievement of a better understanding of post-positivism and greater focus on explicating the philosophical assumptions underpinning all research methods, the distinctions that have long been perceived to exist between qualitative and quantitative methodologies can be confined to the past. Rather methods will be selected solely on the nature of research questions.
The quality and quantity of saliva may be important in defending against pathogens transmitted via the buccal cavity. The aim of the present study was to examine the effect of cycling to exhaustion at moderate and high intensity on various salivary parameters and the time course of recovery. Eighteen male subjects of mixed physical fitness took part in the study. Subjects performed two bouts of exercise on separate occasions at least one week apart. Following an overnight fast, subjects cycled on an electrically braked cycle ergometer at a work rate equivalent to 80% VO2max until exhaustion. On another occasion they cycled on the same ergometer at 55% VO2max for 3 h or to fatigue (whichever was sooner). The order of the rides was randomised. Timed, unstimulated saliva samples were collected pre-exercise, during exercise, at cessation of exercise and at 1, 2.5, 5 and 24 h post-exercise. Saliva samples were analysed for IgA, total protein and osmolality. Saliva flow rate was significantly reduced by exercise (P < 0.01). Saliva IgA concentration, secretion rate and ratio to osmolality increased during exercise (P < 0.01). IgA to protein ratio did not change significantly during exercise. Since saliva protein secretion rate increased during exercise (P < 0.01) it appears that correcting for loss of saliva water by expressing IgA relative to protein is misleading. IgA secretion rate and IgA to osmolality ratio are more appropriate measures and neither parameter was lowered by exercise. The results of this study indicate that exercise may detrimentally affect the quantity of saliva produced, but not the quality of saliva. Furthermore, when exercise is to exhaustion, the intensity of the bout does not appear to influence the saliva response. Neither exercise protocol had any long term effect on saliva as all variables recovered within 1 h post-exercise.
Obesity has significant consequences for the reproductive system, depending upon the amount and distribution of body fat. Epidemiological evidence clearly shows that being overweight contributes to menstrual disorders, infertility, miscarriage, poor pregnancy outcome, impaired fetal well-being and diabetes mellitus. Central adiposity is particularly important in clinical sequelae associated with an increased body mass index. The advent of assisted reproduction highlights the problems of being overweight, and the use of gonadotrophins in ovulation induction and in vitro fertilization is more difficult when the subject is overweight. Weight loss has marked effects on improving the menstrual cycle and promoting spontaneous ovulation and fertility. Results indicate that fertility is improved through exercise and sensible eating patterns when conducted in a group environment. The mechanisms for this are unclear but may be associated with changes in sensitivity to insulin.
Obesity affects ovulation, response to fertility treatment, pregnancy rates and outcome. In this prospective study, a weight loss programme was assessed to determine whether it could help obese infertile women, irrespective of their infertility diagnosis, to achieve a viable pregnancy, ideally without further medical intervention. The subjects underwent a weekly programme aimed at lifestyle changes in relation to exercise and diet for 6 months; those that did not complete the 6 months were treated as a comparison group. Women in the study lost an average of 10.2 kg/m2, with 60 of the 67 anovulatory subjects resuming spontaneous ovulation, 52 achieving a pregnancy (18 spontaneously) and 45 a live birth. The miscarriage rate was 18%, compared to 75% for the same women prior to the programme. Psychometric measurements also improved. None of these changes occurred in the comparison group. The cost savings of the programme were considerable. Prior to the programme, the 67 women had had treatment costing a total of A$550,000 for two live births, a cost of A$275,000 per baby. After the programme, the same women had treatment costing a total of A$210,000 for 45 babies, a cost of A$4600 per baby. Thus weight loss should be considered as a first option for women who are infertile and overweight.
BACKGROUND AND OBJECTIVES: An estimated 4 million new cases of chlamydial infection occur each year. This experiment assessed the effects of a vaginally applied gel formulation of 0.25% chlorhexidine gluconate on chlamydial infection and on the vaginal ecosystem. STUDY DESIGN: Twelve monkeys were treated with a single application of 0.25% chlorhexidine gluconate. These animals were assessed for changes in vaginal flora before and at 30 minutes, 1 day, and 2 days postapplication by microbiologic analysis. Cervical and vaginal tissues were assessed by colposcopy at each time point. Five monkeys received a single application of 0.25% chlorhexidine gluconate gel followed (30 minutes) by a cervical inoculation with Chlamydia trachomatis. Four monkeys were inoculated with Chlamydia only. Cervicovaginal tissues were assessed via modified colposcopy, vaginal swabs were collected for assessment of vaginal flora, and cervical swabs were collected for detection of Chlamydia (culture/ligase chain reaction) at baseline and days 1, 2, and 7 postinoculation. RESULTS: Changes in vaginal flora were minimal in all monkeys. Application of 0.25% chlorhexidine gluconate did not affect adversely vaginal colonization by lactobacilli. All chlamydial infection control monkeys were infected, whereas none of the five monkeys pretreated with chlorhexidine gluconate were positive for C. trachomatis by culture or ligase chain reaction. Colposcopic observations remained largely unchanged in all groups. CONCLUSIONS: A 0.25% chlorhexidine gluconate gel was protective against chlamydial infection in all animals tested, had no adverse effect on the vaginal flora, and had minimal effect on cervicovaginal tissues after a single application.
We examined the effects of a low-carbohydrate (CHO) diet on the plasma glutamine and circulating leukocyte responses to prolonged strenuous exercise. Twelve untrained male subjects cycled for 60 min at 70% of maximal oxygen uptake on two separate occasions, 3 days apart. All subjects performed the first exercise task after a normal diet; they completed the second exercise task after 3 days on either a high-CHO diet (75 +/- 8% CHO, n = 6) or a low-CHO diet (7 +/- 4% CHO, n = 6). The low-CHO diet was associated with a larger rise in plasma cortisol during exercise, a greater fall in the plasma glutamine concentration during recovery, and a larger neutrophilia during the postexercise period. Exercise on the high-CHO diet did not affect levels of plasma glutamine and circulating leukocytes. We conclude that CHO availability can influence the plasma glutamine and circulating leukocyte responses during recovery from intense prolonged exercise.
The myeloid transforming gene Evi-1 encodes a protein with two zinc finger domains, designated ZF1 and ZF2, with distinct DNA binding specificities. For the first time we demonstrate that Evi-1 has transcriptional repressor activity which is directly proportional to the amount of Evi-1 protein in cells. Repression has been observed with two distinct promoters: the minimal HSV-1 tk promoter and a VP16 inducible adenovirus E1b minimal promoter. Optimal repression is DNA binding dependent and is mediated by either ZF1 or a heterologous GAL4 DNA binding domain (GAL4DBD) but is significantly less efficient through the ZF2 binding site. Both GAL4DBD/Evi-1 fusion and non-fusion proteins have been used to map the repressor activity to a proline-rich region located within amino acids 514-724 between the ZF1 and ZF2 domains. Constitutive expression of mutant proteins lacking the repressor domain are defective for transformation of Rat1 fibroblasts demonstrating that this region is required for the oncogenic activity of the Evi-1 protein. These studies show that the Evi-1 gene encodes a transcriptional repressor and has important implications for the mechanism of action of the Evi-1 protein both in development and in the progression of some myeloid leukaemias.
PURPOSE: In a continuation of our search for novel antifungal compounds from higher plants, the standard extract of the bark of Pithecellobium racemosum was found to have good activity against important AIDS-related opportunistic yeasts. METHODS: The extract was subjected to bioguided fractionation using silica gel column chromatography which led to purification of triterpene glycosides. The structures of these compounds were determined by a combination of spectroscopic (IR, NMR, HRMS) and chemical methods. RESULTS: Compound 1 is a new glycoside, 3-O[alpha-L-arabinopyranosyl (1-2)][alpha-L arabinopyranosyl (1-6)]2-acetoamido-2-deoxy-beta-D-glucopyranosyl oleanolic acid and Compound 2 was identified as the known compound 3-O-[alpha-L-arabinopyranosyl (1-2)]alpha-L-arabinopyranosyl (1-6)] 2-acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic acid. CONCLUSIONS: Compound 1 is a new glycoside, 3-O-[alpha-L-arabinopyranosyl (1-2)]alpha-L-arabinopyranosyl (1-6)]-2-acetoamido-2-deoxy-beta-D-glucopyranosyl oleanolic acid and exhibits moderate antifungal activity against T. mentogrophytes, C. albicans and S. cerevisiae with MIC values of 6.25, 12.5 and 12.5 micrograms/ml respectively.
Sieve elements in the phloem of most angiosperms contain proteinaceous filaments and aggregates called P-protein. In the genus Cucurbita, these filaments are composed of two major proteins: PP1, the phloem filament protein, and PP2, the phloem lactin. The gene encoding the phloem filament protein in pumpkin (Cucurbita maxima Duch.) has been isolated and characterized. Nucleotide sequence analysis of the reconstructed gene gPP1 revealed a continuous 2430 bp protein coding sequence, with no introns, encoding an 809 amino acid polypeptide. The deduced polypeptide had characteristics of PP1 and contained a 15 amino acid sequence determined by N-terminal peptide sequence analysis of PP1. The sequence of PP1 was highly repetitive with four 200 amino acid sequence domains containing structural motifs in common with cysteine proteinase inhibitors. Expression of the PP1 gene was detected in roots, hypocotyls, cotyledons, stems, and leaves of pumpkin plants. PP1 and its mRNA accumulated in pumpkin hypocotyls during the period of rapid hypocotyl elongation after which mRNA levels declined, while protein levels remained elevated. PP1 was immunolocalized in slime plugs and P-protein bodies in sieve elements of the phloem. Occasionally, PP1 was detected in companion cells. PP1 mRNA was localized by in situ hybridization in companion cells at early stages of vascular differentiation. The developmental accumulation and localization of PP1 and its mRNA paralleled the phloem lactin, further suggesting an interaction between these phloem-specific proteins.
To evaluate the effects of antimicrobial and antiinflammatory drugs on oviductal pathology in chronic chlamydial upper genital tract infection, the fallopian tubes of 40 female Macaca nemestrina were inoculated with Chlamydia trachomatis and randomly assigned to treatment with doxycycline (n = 10), doxycycline plus ibuprofen (n = 10), doxycycline plus triamcinolone (n = 10), or placebo (n = 10). Before therapy, all animals were positive for culture or ligase chain reaction (or both), and laparoscopy demonstrated the presence of upper genital tract pathology. After therapy, cervical cultures remained positive in 5 animals given placebo versus 0 given doxycycline alone (P = .03), 0 given doxycycline plus ibuprofen (P = .03), and 1 given doxycycline plus triamcinolone (P = .14). At hysterectomy, neither gross nor histologic pathology was affected by any of the treatment regimens, but immunocytochemistry and in situ hybridization evidence of persistent tubal infection was significantly more frequent among animals given placebo or doxycycline plus antiinflammatory agents than among those given doxycycline alone.