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Biomedical subjects

J B Walker

Publications and source records attributed to J B Walker.

At least 19 recordsLinked to original sources

Enzymatic synthesis of aminocyclitol moieties of aminoglycoside antibiotics from inositol by Streptomyces spp.: detection of glutamine-aminocyclitol aminotransferase and diaminocyclitol aminotransferase activities in a spectinomycin producer.

Extracts of stationary-phase mycelia of the spectinomycin producer Streptomyces flavopersicus ATCC 19756 catalyzed inositol dehydrogenase, L-glutamine:inosose aminotransferase, 2-epi-streptamine:inosose aminotransferase, streptamine:inosose aminotransferase, N3-methyl-2-deoxystreptamine:inosose aminotransferase, and aminodeoxy-scyllo-inositol:inosose aminotransferase reactions, as detected with a new rapid assay procedure. These results suggest that one or both amino groups of the N1,N3-dimethyl-2-epi-streptamine moiety of spectinomycin are derived by transamination from the alpha-amino group of L-glutamine. An enzymatic procedure for distinguishing among N1- and N3-monomethyl diaminocyclitol derivatives and their diaminocyclitol biosynthetic precursors is described. A scheme showing key roles of glutamine-aminocyclitol aminotransferases in biosynthesis of major aminoglycoside antibiotics is presented.

Glutamine

Rhipicephalus interventus sp. nov. (Acari: Ixodidae), a new tick species closely related to Rhipicephalus tricuspis Dönitz, 1906 and Rhipicephalus Iunulatus Neumann, 1907, from east and central Africa.

Descriptions of the adults of this new species are given, together with information on its hosts and distribution. Previously it was referred to briefly by Walker, Keirans, pegram & Clifford (1988), who noted that in many respects it is intermediate in appearance between R. tricuspis and R. Iunulatus.

Africa, Central

GM-1 ganglioside administration combined with physical therapy restores ambulation in humans with chronic spinal cord injury.

In a randomized double-blind cross-over study, humans with chronic spinal cord injury received ganglioside GM-1 or placebo for 2 months. GM-1, administered intravenously at a dose of 100 mg, 6 days a week, resulted in a statistically significant improvement of motor scores (P < 0.05), whether administered before or after 2 months of placebo. There was no placebo effect on motor scores. Subjects who received GM-1 before placebo maintained their improvement during the placebo phase. Subjects who received GM-1 ambulated with a reciprocal gait, using orthotics, for longer distances and at a faster rate whether the drug was administered before or after placebo. These results constitute the first finding that any chemical substance improves locomotion in human chronic spinal cord injury.

Adult

Quality assurance of ultrasound imaging instruments by monitoring the monitor.

Ultrasound quality assurance (QA) is a means of assuring the constant performance of an ultrasound instrument. A novel 'ultrasound image analyser' has been developed to allow objective, accurate and repeatable measurement of the image displayed on the ultrasound screen, i.e. as seen by the operator. The analyser uses a television camera/framestore combination to digitize and analyse this image. A QA scheme is described along with the procedures necessary to obtain a repeatable measurement of the image so that comparisons with earlier good images can be made. These include repositioning the camera and resetting the video display characteristics. The advantages of using the analyser over other methods are discussed. It is concluded that the analyser has distinct advantages over subjective image assessment methods and will be a valuable addition to current ultrasound QA programmes.

Humans

Rhipicephalus aquatilis sp. nov. (Acari: Ixodidae), a new tick species parasitic mainly on the sitatunga, Tragelaphus spekei, in east and central Africa.

This tick, originally referred to as Rhipicephalus species III by Yeoman & Walker (1967), was first collected from a sitatunga, Tragelaphus spekei, and then occasionally from cattle, in Tanzania. Further collections, mostly from sitatunga, have since been seen from Uganda and Zambia. Descriptions of the adults of this species are given, together with information on their hosts and their distribution.

Africa, Central

Rhipicephalus exophthalmos sp. nov., a new tick species from southern Africa, and redescription of Rhipicephalus oculatus Neumann, 1901, with which it has hitherto been confused (Acari: Ixodida: Ixodidae).

Rhipicephalus exophthalmos sp. nov., a species which has in the past been confused with Rhipicephalus oculatus Neumann, 1901, is described and illustrated from laboratory-reared specimens. Preferred hosts for the adults of this tick are various domestic and wild ungulates and hares. It is widely distributed in Namibia and in the southeastern Cape Province, South Africa, with only scattered records from elsewhere. The adults of R. oculatus are redescribed and illustrated, and the immature stages are described and illustrated for the first time. All stages feed virtually exclusively on leporids. It is common in parts of the eastern and southern Cape Province, with few records as yet from other parts of South Africa and Namibia.

Africa, Southern

Improving practice through research: the case of heparin vs. saline for peripheral intermittent infusion devices.

Peripheral intermittent infusion devices are commonly used to administer periodic doses of medications to adults and children. Research findings provide a strong base for changing practice to using saline instead of heparin to flush these devices in children over 28 days old and in adults. This research-based change in practice will enhance the quality of care that patients receive and decrease the costs of their care.

Adolescent

A review of the ixodid ticks (Acari, Ixodidae) occurring in southern Africa.

Eighty-three species of ixodid ticks, as well as several entities that have yet to be described, occur in the Republic of South Africa plus the 4 independent states lying within its borders (Bophuthatswana, Venda, Transkei and Ciskei) and in Namibia, Botswana, Lesotho and Swaziland. They belong to the following genera: Amblyomma (8 spp.); Aponomma (3 spp.); Boophilus (2 spp.); Cosmiomma (1 sp.); Dermacentor (1 sp.); Haemaphysalis (10 spp.); Hyalomma (2 spp., one of them with 2 subspp.); Ixodes (25 spp.); Margaropus (1 sp.); Rhipicentor (2 spp.), and Rhipicephalus (28 spp). The history of tick research in this region is reviewed briefly and advances made by the major contributors to our knowledge are highlighted. Short comments on each genus are given. These are followed by information on every species known to occur in the region, presented under the following headings: Species diagnosis, under which references to relevant descriptions are listed and, where appropriate, notes on commonly used synonyms, related species and identification problems are included; hosts, indicating whenever possible the preferences of both the adults and the immature stages, as well as differentiating between common and incidental hosts, and distribution in terms of political (not ecological) divisions.

Africa, Southern

Geographical information systems for studying the epidemiology of cattle diseases caused by Theileria parva.

Data on selected variables which influence the epidemiology of cattle diseases caused by Theileria parva were assembled and entered in a computerised geographical information system. Variables studied included the distributions of major hosts (cattle and buffalo), the vector ticks (Rhipicephalus appendiculatus and related species) and the reported presence of East Coast fever, corridor disease and January disease. In addition, the distribution of climatic suitability for R appendiculatus was assessed using the model CLIMEX run on an interpolated climate database developed for Africa. Distribution maps of each variable were produced. The potential value of geographical information systems in studies of disease epidemiology and control is discussed, with examples of how sensitivity may be enhanced by the inclusion of additional variables. In addition, subject areas in which poor data quality and inadequate data standardisation may limit the use of these systems are identified and discussed.

Africa

Randomized, double-blind comparison of the efficacies, costs, and vaginal flora alterations with single-dose ceftriaxone and multidose cefazolin prophylaxis in vaginal hysterectomy.

A comparison of efficacies, costs, and effects on vaginal microflora of one preoperative and three postoperative 1-g doses of cefazolin versus those of one preoperative 1-g dose of ceftriaxone was done with 65 and 73 women, respectively, undergoing elective vaginal hysterectomy. Patient infection rates were not statistically different between the cefazolin group (six events in 6 of 73 patients [8.2%]) and the ceftriaxone group (11 events in 9 of 65 patients [13.8%]). Side effects, including diarrhea, were minimal and similar between the two groups. Significant shifts in the cervicovaginal microflora of the patients occurred postoperatively, with a marked increase in enterococci and a drop in nonenterococcal streptococci. No shifts among aerobic, facultative gram-negative rods and staphylococci were observed. Among the anaerobes, a significant decrease in the number of patients harboring nonsporulating, gram-positive rods and a less striking concomitant increase in Bacteriodes species and members of the family Peptococcaceae were noted. No qualitative differences were noted between the two groups that received prophylactic therapy. Aside from enterococci, cefazolin or ceftriaxone resistance among vaginal isolates (greater than or equal to 10(3)/ml) was minimal. Selection of resistant isolates was not different between the treatment groups. We could not detect a difference between a single 1-g dose of ceftriaxone and multidose cefazolin for infection prophylaxis in patients undergoing a vaginal hysterectomy. However, the total acquisition, preparation, and administration costs were greater for the ceftriaxone regimen than they were for the cefazolin regimen. Cefazolin should therefore remain the drug of choice for infection prophylaxis in uncomplicated vaginal hysterectomies.

Bacteria

Possible evolutionary relationships between streptomycin and bluensomycin biosynthetic pathways: detection of novel inositol kinase and O-carbamoyltransferase activities.

Bluensomycin (glebomycin) is an aminocyclitol antibiotic that differs structurally from dihydrostreptomycin in having bluensidine (1D-1-O-carbamoyl-3-guanidinodeoxy-scyllo-inositol) rather than streptidine (1,3-diguanidino-1,3-dideoxy-scyllo-inositol) as its aminocyclitol moiety. Extracts of the bluensomycin producer Streptomyces hygroscopicus form glebosus ATCC 14607 (S. glebosus) were found to have aminodeoxy-scyllo-inositol kinase activity but to lack 1D-1-guanidino-3-amino-1,3-dideoxy-scyllo-inositol kinase activity, showing for the first time that these two reactions in streptomycin producers must be catalyzed by different enzymes. S. glebosus extracts therefore possess the same five enzymes required for synthesis of guanidinodeoxy-scyllo-inositol from myo-inositol that are found in streptomycin producers but lack the next three of the four enzymes found in streptomycin producers that are required to synthesize the second guanidino group of streptidine-P. In place of a second guanidino group, S. glebosus extracts were found to catalyze a Mg2(+)-dependent carbamoylation of guanidinodeoxy-scyllo-inositol to form bluensidine, followed by a phosphorylation to form bluensidine-P. The novel carbamoyl-P:guanidinodeoxy-scyllo-inositol O-carbamoyltransferase and ATP:bluensidine phosphotransferase activities were not detected in streptomycin producers or in S. glebosus during its early rapid growth phase. Free bluensidine appears to be a normal intermediate in bluensomycin biosynthesis, in contrast to the case of streptomycin biosynthesis; in the latter, although exogenous streptidine can enter the pathway via streptidine-P, free streptidine is not an intermediate in the endogenous biosynthetic pathway. Comparison of the streptomycin and bluensomycin biosynthetic pathways provides a unique opportunity to evaluate those proposed mechanisms for the evolutionary acquisition of new biosynthetic capabilities that involve gene duplication and subsequent mutational changes in one member of the pair. In this model, there are at least five pairs of enzymes catalyzing analogous reactions that can be analyzed for homology at both the protein and DNA levels, including two putative pairs of inositol kinases detected in this study.

Biological Evolution

Two new species of ticks from southern Africa whose adults parasitize the feet of ungulates: Rhipicephalus lounsburyi n. sp. and Rhipicephalus neumanni n. sp. (Ixodoidea, Ixodidae).

Theiler & Robinson (1953) described, as Rhipicephalus follis Dönitz, 1910, a tick species originating from Dordrecht, Eastern Cape Province. A comparison of this tick with the syntypes of R. follis has now shown, though, that these 2 entities are different and it is therefore redescribed below as Rhipicephalus lounsburyi n. sp. Its adults parasitize sheep and various wild ungulates, attaching primarily on their feet. The hosts of the immature stages are still unknown. It has now been recorded from several places in the Eastern Cape; once in Natal, at Impendle, and in the Western Cape near Swellendam and between Clanwilliam and Graafwater. A second species, which has in the past been confused with the dassie parasite, Rhipicephalus distinctus Bedford, 1932, is described as Rhipicephalus neumanni n. sp. Its adults also attach on the feet of sheep and goats. The hosts of the immature stages are unknown. It has been widely recorded in the Bethanien and Keetmanshoop Districts of Namibia and, in South Africa, from scattered localities in the Karoo.

Animals

Reactions catalyzed by purified L-glutamine: keto-scyllo-inositol aminotransferase, an enzyme required for biosynthesis of aminocyclitol antibiotics.

Dialyzed extracts of the gentamicin producer Micromonospora purpurea catalyze reactions which represent transaminations proposed for 2-deoxystreptamine biosynthesis. To determine whether these transaminations were catalyzed by a single aminotransferase or by multiple enzymes, we purified and characterized an L-glutamine:keto-scyllo-inositol aminotransferase from M. purpurea. This enzyme was purified 130- to 150-fold from late-log-phase mycelia of both wild-type M. purpurea and a 2-deoxystreptamine-less idiotroph. The cofactor pyridoxal phosphate was found to be tightly bound to the enzyme, and spectral analysis demonstrated its participation in the transamination reactions of this enzyme. The major physiological amino donor for the enzyme appears to be L-glutamine; the keto acid product derived from glutamine was characterized as 2-ketoglutaramate, indicating that the alpha amino group of glutamine participates in the transamination. We found that crude extracts contained omega-amidase activity, which may render transaminations with glutamine irreversible in vivo. The substrate specificity of the aminotransferase was shown to be restricted to deoxycyclitols, monoaminocyclitols, and diaminocyclitols, glutamine, and 2-ketoglutaramate, which contrasts with the broader substrate specificity of mammalian glutamine aminotransferase. The appearance of the enzyme in late-log phase, coupled with its narrow substrate specificity, indicates that it participates predominantly in 2-deoxystreptamine biosynthesis rather than in general metabolism. The enzyme catalyzes reactions which represent both transamination steps of 2-deoxystreptamine biosynthesis. Although copurification of two aminotransferases cannot be ruled out, our data are consistent with the participation of a single aminotransferase in the formation of both amino groups of 2-deoxystreptamine during biosynthesis by M. purpurea. We propose that this aminotransferase participates in a key initial step in the biosynthesis of most aminocyclitol antibiotics.

Amidohydrolases

Utilization of the synthetic phosphagen cyclocreatine phosphate by a simple brain model during stimulation by neuroexcitatory amino acids.

The ability of 1-carboxymethyl-2-imino-3-phosphonoimidazolidine (cyclocreatine-P), accumulated by a simple brain model, to function as a supplemental synthetic phosphagen and respond to the decreases in cytosolic ATP/free ADP ratios that occur during prolonged stimulation by various excitatory amino acids was investigated. Suspensions of chopped whole brain from 11- to 14-day-old chick embryos were incubated with 30 mM cyclocreatine for 90 min, resulting in accumulation of 100 mumol/g dry weight of cyclocreatine-P, and then incubated for up to 1 h with a series of excitatory amino acids of widely differing potencies. Under these conditions net utilization of cyclocreatine-P was detected in response to stimulation by the following neuroexcitatory compounds at the indicated threshold concentrations: kainate (20 microM), N-methyl-DL-aspartate (20 microM), L-homocysteate (20 microM), L-glutamate (200 microM), D-glutamate (200 microM), L-aspartate (2 mM), DL-2-amino-3-phosphonopropionate (2 mM), and DL-2-amino-4-phosphonobutyrate (2 mM). Significant increases in water content of chick embryo brain minces accompanied stimulation by excitatory amino acids. It is suggested that changes in water content or cyclocreatine-P levels in this sensitive brain model might be utilized in automatable screening procedures for detecting novel antagonists and/or new agonists of excitatory amino acids.

Adenosine Diphosphate

Enhanced ability of skeletal muscle containing cyclocreatine phosphate to sustain ATP levels during ischemia following beta-adrenergic stimulation.

Breast muscle of young chicks fed chow diets containing the creatine analog 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine) accumulated up to 40 mumol/g wet weight of the synthetic phosphagen 1-carboxymethyl-2-imino-3-phosphonoimidazolidine (cyclocreatine-P2-). ATP levels were sustained at high values substantially longer in breast muscle of cyclocreatine-fed chicks, compared to control-fed chicks, during total ischemia initiated 2 h after injection of both groups with the beta-adrenergic agonist isoproterenol (5 mg/kg subcutaneous). For example, in chicks fed 0.5% cyclocreatine for 10-19 days ATP levels in isoproterenol-stimulated breast muscles after 1 h of ischemia at 37 degrees C were 6.1 mumol/g, compared to 1.9 mumol/g for the control-fed group, and after 2 h of ischemia were 3.5 mumol/g compared to 0.6 mumol/g for controls. Creatine-P reserves in isoproterenol-stimulated breast muscles of all dietary groups were essentially exhausted within the first hour of ischemia. In contrast, breast muscle of chicks fed either 1 or 0.5% cyclocreatine still contained 28 and 19 mumol/g of cyclocreatine-P, respectively, after 1 h of ischemia; after 2 h of ischemia, the respective cyclocreatine-P values were 20 and 13 mumol/g. Isoproterenol-stimulated chick breast muscle provides the first skeletal muscle model system for studying the molecular mechanisms by which dietary cyclocreatine helps sustain ATP levels during ischemia. Although adaptive factors are also involved, it is suggested that a significant portion of the ATP-sustaining activity of dietary cyclocreatine in ischemic breast muscle can be attributed to the unique thermodynamic properties of the accumulated cyclocreatine-P. These properties enable cyclocreatine-P to continue to thermodynamically buffer the adenylate system and transport high energy phosphate throughout the long muscle fibers at cytosolic pH values and phosphorylation potentials well below the range where the creatine-P system can function effectively. Synergism between glycolysis and this long-acting synthetic phosphagen might well help delay depletion of ATP levels in skeletal muscles during ischemia. Cyclocreatine feeding provides a unique experimental tool for quantitative evaluation of the proposed protective role of ATP against irreversible cellular damage in skeletal and cardiac muscles during ischemic episodes.

Adenosine Triphosphate

The tick vectors of Cowdria ruminantium (Ixodoidea, Ixodidae, genus Amblyomma) and their distribution.

Twelve species of Amblyomma are presently known to be capable of transmitting Cowdria ruminantium. Of these A. variegatum is the most important and widely distributed vector in Africa. It has also extended its range considerably outside this continent, eastward to the Yemen Arab Republic and to the islands of Madagascar, Réunion and Mauritius, and westward to the Cape Verde islands and to some of the West Indian islands. A. hebraeum is probably the only field vector in most parts of southern Africa. A 3rd species, A. lepidum, is known to have been involved in field outbreaks of heartwater in the Sudan. Two other species are also currently regarded as field vectors of Cowdria: A. astrion on the islands of São Tomé and Principe, and A. pomposum in Angola. Another 5 African species (A. cohaerens, A. gemma, A. tholloni, A. sparsum and A. marmoreum) have proved to be capable of transmitting heartwater in the laboratory, as have 2 American species (A. maculatum and A. cajennense), but none of these ticks have been implicated in field outbreaks of the disease.

Africa