Potential for glucosyltransferase-based synthetic peptides in a dental caries vaccine.
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Amino Acid Sequence↗
Biomedical subjects
D J Smith
Publications and source records attributed to D J Smith.
Spinal nonadrenergic imidazoline receptors do not mediate the antinociceptive action of intrathecal clonidine in the rat.
The intrathecal administration of clonidine to rats results in profound antinociception which is thought to be mediated through an interaction of the agonist with spinal alpha-2 adrenergic receptors. However, clonidine has been shown to also interact with nonadrenergic imidazoline receptors. Consequently, this study was undertaken to determine if nonadrenergic imidazoline receptors are present in the rat spinal cord, and the extent to which they are involved in the antinociceptive action of spinally administered clonidine. By using the tail-flick test, the antinociceptive action of spinally administered clonidine was found to be blocked completely by the intrathecal administration of the imidazoline idazoxan. Similarly, yohimbine (a nonimidazoline alpha-2 adrenergic antagonist) also blocked completely the antinociceptive action of clonidine. Results of radioligand binding studies demonstrated that norepinephrine did not interact with approximately 20% of all specific spinal sites labeled by 4 nM [3H]clonidine, indicating the presence of nonadrenergic spinal sites. Affinity data obtained from competition binding assays demonstrated that the spinal nonadrenergic sites labeled by [3H]clonidine possess little affinity for yohimbine. Therefore, nonadrenergic imidazoline receptors are not involved in the antinociceptive action of spinally administered clonidine.
Adrenergic alpha-Antagonists↗
Immediate transverse rectus abdominis musculocutaneous flap reconstruction after mastectomy.
BACKGROUND: This study examines the early and long-term outcomes of immediate transverse rectus abdominis musculocutaneous (TRAM) reconstruction of the breast after mastectomy. STUDY DESIGN: The records of all patients undergoing mastectomy and immediate TRAM breast reconstruction between December 1989 and October 1993 were reviewed retrospectively using hospital and breast care center databases. RESULTS: Fifty-three patients underwent a total of 73 immediate TRAM breast reconstructions. Reconstruction was successfully completed in all patients, using 46 pedicle flaps and 27 free tissue transfers. There were no flap losses or cardiopulmonary complications. Overall, the complication rate was 26 percent (29 percent for pedicle TRAM and 22 percent for free TRAM flaps). The median follow-up period among the 53 patients was 22.6 months (range of three to 48 months). All patients employed preoperatively resumed their occupations postoperatively. CONCLUSIONS: Our experience indicates that immediate TRAM breast reconstruction is a safe and viable option for patients seeking reconstruction at the time of mastectomy.
Adult↗
Repetitive exposure to the hot-plate test produces stress induced analgesia and alters beta-endorphin neuronal transmission within the periaqueductal gray of the rat.
Repetitive exposure of rats to a hot plate induced a novel non-opioid form of stress induced analgesia. The exposure caused a persistent 1.5-2 s increase in tail flick latency which was not attenuated by systemic naltrexone, but was completely inhibited by systemic MK-801. Concomitantly, alterations occurred in the ability to pharmacologically distinguish multiple beta-endorphin receptors in the periaqueductal gray. Thus, in response to different forms of stress, different pathways may be activated by beta-endorphin, resulting in stress induced analgesias with varied pharmacological characteristics (e.g., opioid and non-opioid).
Amino Acid Sequence↗
Nuclei within the rostral ventromedial medulla mediating morphine antinociception from the periaqueductal gray.
The relative contributions of nuclei within the rostral ventromedial medulla (RVM) involved in mediating morphine induced antinociception from the periaqueductal gray (PAG) were examined. Lidocaine injections (4%) at the time of morphine's maximal response were used to provide a localized neural block and were administered in the nucleus raphe magnus/reticularis gigantocellularis pars alpha (RMg/GiA; commonly referred to as RMg), reticularis gigantocellularis (Gi) and reticularis paragigantocellularis lateralis (LPGi). Microinjection of morphine (6 nmol; 0.5 microliter) into the PAG of awake rats produced an inhibition of the tail-flick reflex that was maximal after 30 min. This response was unaffected by a single medial lidocaine injection (0.5 microliter) into the RMg/GiA or Gi, bilateral injections into the Gi or LPGi or triple injections that included both the RMg/GiA and LPGi. A partial, non-significant block of morphine's response was observed either by bilateral injections (0.5 microliter) into both the Gi and LPGi (% inhibition = 16.4 +/- 24.8) or by bilateral injections in the LPGi and a single medial injection into the Gi (% inhibition = 41.5 +/- 29.8). However, injection of a greater volume of lidocaine (1 microliter) into the RMg/GiA or bilaterally into the LPGi affected adjacent medial and lateral tissue, and completely inhibited morphine's response. Furthermore, triple injections of lidocaine (0.5 microliter) into the Gi or bilateral injections (0.5 microliter) into the Gi and a single medial injection into the RMg/GiA completely blocked morphine's antinociceptive response. These results indicate that morphine antinociception from the PAG is mediated by a large volume of tissue in the RVM containing nuclei located both medially and laterally. Additionally, the principal nuclei involved in this response appear to be the Gi and RMg/GiA.
Analgesics↗
Localization of the antinociceptive and antianalgesic effects of neurotensin within the rostral ventromedial medulla.
Triple microinjections of neurotensin (10 nmol each), which occupied a large volume of tissue within the nucleus reticularis gigantocellularis (Gi), produced an inhibition of the tail-flick reflex in awake rats. This effect was less than that previously observed by a single injection (10 nmol) into the nucleus raphe magnus (RMg) (see ref. [25]). Bilateral injections of neurotensin (10 nmol each) into the nucleus reticularis paragigantocellularis lateralis (LPGi) had no effect. The neurotensin antagonist [D-Trp11]-neurotensin (3 pmol) was previously found to enhance morphine, but not beta-endorphin antinociception from the periaqueductal gray (PAG) when injected into the RMg. A similar enhancement of morphine, but not beta-endorphin antinociception from the PAG was observed in the current study by [D-Trp11]-neurotensin injections into the bilateral LPGi, bilateral Gi, or medial Gi. These data suggest that neurotensinergic projections from the PAG function in an antianalgesic manner throughout the RVM during morphine, but not beta-endorphin antinociception. The antinociceptive effect of neurotensin, on the other hand, is more localized.
Analgesics↗
Crystallization and preliminary X-ray analysis of Candida albicans phosphomannose isomerase.
Crystals of recombinant phosphomannose isomerase from Candida albicans have been obtained in a form suitable for X-ray diffraction analysis. The enzyme plays a key role in the biosynthesis of the mannan component of the fungal cell wall. It crystallizes in monoclinic space group C2, with cell dimensions a = 124.9 A, b = 52.9 A, c = 85.9 A and beta = 127.4 degrees. The crystals diffract to Bragg spacings beyond 1.7 A, native data have been collected to 2.4 A and a search for heavy-metal derivatives is in progress. The asymmetric unit contains one molecule of the enzyme (M(r) approximately 49,000) with a Vm of 2.3 A3/Da.
Candida albicans↗
Purification, cDNA cloning and heterologous expression of human phosphomannose isomerase.
Phosphomannose isomerase catalyses the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions. Three classes of enzymes possessing phosphomannose-isomerase activity have been identified in bacteria and lower eukaryotes. We have purified human phosphomannose isomerase to homogeneity from placental tissue. Protein sequence information obtained from internal fragments of the protein was used to design degenerate oligonucleotides which were used to amplify a fragment of a human phosphomannose-isomerase cDNA. A full-length cDNA was isolated from a human testes lambda gt11 library using this fragment as a probe. The cDNA encoded a protein with significant sequence identity to fungal and some bacterial phosphomannose isomerases but was unrelated to those from other bacteria. Based on amino acid sequence identity we propose a classification system for enzymes with phosphomannose-isomerase activity. The cDNA, under the control of the GAL1 promoter, was expressed in a Saccharomyces cerevisiae strain from which the native gene encoding phosphomannose isomerase had been deleted. The human enzyme was found to be able to functionally substitute for the yeast enzyme. Phosphomannose-isomerase mRNA was found in all human tissues tested but was more highly expressed in heart, brain and skeletal muscle. The cDNA was expressed in Escherichia coli permitting the isolation of pure recombinant protein which will be used for kinetic and structural studies.
Amino Acid Sequence↗
Rigid internal fixation of the sternum in postoperative mediastinitis.
OBJECTIVE: The current standard treatment of mediastinitis following median sternotomy is radical sternal débridement and obliteration of anterior mediastinal dead space with muscle or omental flaps. This report describes and reviews our experiences with a new technique of sternal salvage based on osseous quantitative bacteriologic assessment and rigid fixation in patients with postoperative mediastinitis. DESIGN: A retrospective review of 29 patients treated with sternal rigid internal fixation. SETTING: Two tertiary care academic medical centers in Chicago, Ill, and Ann Arbor, Mich. PATIENTS: Patients with postoperative mediastinitis following median sternotomy who underwent rigid internal fixation of retained sternum. INTERVENTION: Following débridement, quantitative bacteriologic assessment and sternal vascularity were assessed. Sternal segments with good vascularity and in bacteriologic balance were anatomically reduced and rigidly fixed to each other with titanium miniplates in 24 patients with postoperative mediastinitis. Five of the 29 patients, at high risk for mediastinitis, underwent rigid internal fixation immediately after their cardiac procedure. MAIN OUTCOME MEASURES: Resolution of infection, wounds remaining closed, and stable sternums. RESULTS: Bony union was obtained in 27 (93%) of 29 patients. The postoperative hospital stay ranged from 5 to 84 days, with a mean stay of 17 days and a median stay of 7 days. Length of stay was directly related to pulmonary function, which correlated with preoperative intubation status. CONCLUSIONS: Radical sternal débridement may not be necessary in all patients with postoperative mediastinitis following median sternotomy. Sternal salvage can safely and reliably be performed with a combination of clinical assessment of vascularity and osseous quantitative bacteriologic assessment. Anatomic reduction of the viable sternal segments is possible even in severely osteoporotic bone.
Adolescent↗
Seroepidemiological associations between tuberculosis, malaria, hepatitis B, and AIDS in West Africa.
Serum samples from 51 patients with malaria, 35 patients with hepatitis B virus infection, 111 patients with tuberculosis, and 166 healthy controls were studied to determine any associations between tuberculosis, malaria, hepatitis B, and AIDS in Nigeria, West Africa. All serum samples were examined for the presence of HIV-1/HIV-2, hepatitis B virus surface antigen (HBsAg), and malaria antibodies. Only one patient was HIV-1 antibody-positive and none HIV-2 antibody-positive. Statistical associations were found between the presence of malaria antibody titres on the one hand and a diagnosis of hepatitis B virus infection (P < 0.05) or tuberculosis (P < 0.05). A stronger association (P < 0.001) was found between the presence of HBsAg and tuberculosis suggesting that HBsAg carriers are at higher risk of contracting tuberculosis.
Acquired Immunodeficiency Syndrome↗
The role of xanthine oxidase and xanthine dehydrogenase in skin ischemia.
The importance of sequential events which lead to skin necrosis has significant implications in trauma, vascular injury, and wound healing. In this series of experiments, we tested the hypothesis that xanthine oxidase (XO) activity was increased along an ischemic gradient of a skin flap and that the XO enzyme activity correlated with an increase in neutrophils. There were two animal groups in which the skin flaps were raised and assayed at 0, 1, or 6 hr. In the other group, they were created as bipedicle flaps for 7 days, before the distal attachment was divided and the tissue assayed. In the acutely raised flaps, some animals were treated with the XO inhibitor, allopurinol. Xanthine dehydrogenase (XD) and XO activity was measured with a fluorometric pterin assay and neutrophil concentration was measured using a myeloperoxidase marker. In this model, there was consistent skin necrosis in the distal end of the skin flap (48 +/- 8%). The data showed that both XD and XO activity in the distal ends was statistically significantly increased over the sham control or proximal ends of the skin flaps at 1 hr (P < 0.05). XO activity remained elevated in the distal ends at 6 hr. Allopurinol significantly reduced the neutrophil concentrations in the distal ends of the skin flaps when compared to untreated animals (P < 0.05). Moreover, allopurinol reduced skin necrosis to 12 +/- 1%. Preconditioning of the skin flap reduced the XO activity to sham control levels. The observations implicate XO activity as source of free radical injury in skin necrosis seen in random skin flaps.(ABSTRACT TRUNCATED AT 250 WORDS)
Allopurinol↗
dT diaphorase: increased enzyme activity and mRNA expression in oxidant stress of skin.
DT diaphorase is a flavoprotein that enzymatically transfers two electrons from quinones as intermediate substrates and has been reported to increase its activity in the liver after exposure to toxicants. In this series of experiments, we tested the hypothesis that DT diaphorase also increases its activity after exposure to oxidants following gradient ischemia in skin. Using dorsal rat flaps, oxidant stress was induced immediately or during a 7-day period of preconditioning as a bipedicle flap before the distal attachment was divided. DT diaphorase activity (delta Abs/min/100 g) or expression of message was measured during the period of preconditioning to determine the relationship between skin survival, enzyme activity, and expression of message. There was 4.7 +/- 0.8 cm of skin necrosis in the distal end of acute flaps while the preconditioned flaps had no skin necrosis after the distal attachment was divided. In the acute flaps, the DT diaphorase activity was equal throughout the flap for the first 6 hr. After 24 hr of ischemia, the DT diaphorase activity was significantly higher in the proximal end of the flap (1.83 +/- 0.21 delta Abs/min/100 g) than that in the distal end (0.005 +/- 0.01 delta Abs/min/100 g), which was significant (P < 0.05). In the preconditioned flaps, enzyme activity did not increase but there was as 50-fold increase in DT diaphorase activity at the distal end 24 hr after they were divided (P < 0.05). Maximal enzyme induction of DT diaphorase activity occurred after 4 days of preconditioning and correlated with the maximal expression of mRNA. These studies provide the first evidence that DT diaphorase enzyme activity is inducible after oxidant stress. The data also suggests that DT activity remains elevated for at least 6 hr of ischemia and may be a potential source of anti-oxidant activity in ischemic skin.
Animals↗
What is infection?
Wound colonization by bacteria is not always the same as invasive infection. Furthermore, the classic definition of infection does not always aid the clinician in determining whether a patient is in the process of developing life-threatening sepsis. Although research efforts have focused on identification and quantification of organisms involved, the predictive value of this variable is limited. Other variables, such as the nature of the organism, nature of the wound, and nature of the host's defense mechanisms must also be considered. For instance, large acute wounds have been found to react differently to skin flora organisms than small, chronic, ulcerative wounds. Careful and frequent patient and wound assessment is still required to predict if and when offending organisms, their toxins, or both reach sufficient concentrations to overwhelm their local host defenses.
Bacterial Physiological Phenomena↗
Burn wounds: infection and healing.
Early wound closure is the ultimate goal of burn care. While excisional therapy is necessary in the treatment of both large, full-thickness and deep, partial skin-thickness burns, the majority of burns are superficial partial skin-thickness injuries requiring a different clinical approach. In superficial wounds, cosmetic and functional restoration in conjunction with relief from pain and prevention of infection is as important as rapid wound closure. The moist wound healing associated with hydrocolloid dressings may provide an alternative treatment modality for certain partial-thickness injuries. In comparable wounds, these dressings produce good functional and cosmetic results, rapid reepithelialization, and improved patient comfort.
Burns↗
Donor site repair.
Delayed healing of skin donor sites may be costly and life threatening, especially in patients with large body-surface area burns. A donor site dressing should maximize the ability of the wound to heal without increasing the risk of local infection, systemic infection, or both. Specifically, the possibility of a secondary infection may either slow the healing process or ultimately convert the donor site to a full-thickness wound. A number of materials, ranging from gauze to biological agents, have been investigated for use as donor site dressings. The use of hydrocolloids for donor sites has been studied extensively, and, compared with conventional dressings, improved healing rates are reported. Our recent study using a hydrocolloid dressing confirmed earlier research showing fewer infections and more rapid donor site healing.
Bacterial Physiological Phenomena↗
Effects of high volume and/or intense exercise on selected blood chemistry parameters.
The goal of athletic training is to provide the body with a stimulus to adapt, increasing the capacity of the various systems to perform increased work loads. However, the magnitude of the stress must be large enough to induce the synthesis of new enzymes, tissues, and yet not so large that the biochemical and physiological processes of recovery are depressed. As each individual undergoes this process at a different rate, objective evaluation of the level of fatigue and adaptation is of enormous value in directing the training program of an athlete. The role of iron in the body is such that this element can be used as a marker of both adaptation to training and as an indicator of an acute inflammatory response to exercise. The various clinical measurements of iron in transport, storage, and in hematological parameters are discussed in this paper, relative to athletic populations. In addition expected changes in the level of the acute inflammatory protein, alpha 1-antitrypsin are also discussed relative to acute and chronic training protocols. Data is presented indicating that measurement of serum iron, transferrin, serum ferritin, and alpha 1-antitrypsin can be used to differentiate between an inflammatory response to tissue damage and infection. These parameters can also provide information as to the state of recovery, or lack thereof, experienced by an athlete to both acute and chronic training programs. The use of biochemical markers can help to avoid an overstress situation.
Acute-Phase Reaction↗
Atherosclerosis in mice: getting to the heart of a polygenic disorder.
The mouse is being increasingly used as a model system for understanding the common and complex polygenic condition of atherosclerosis. Mice have been created in which genes involved in this condition have been overexpressed or have been altered by gene targeting. Here, we concentrate on recent experiments that use transgenic and gene knockout mice as an in vivo assay system to unravel the interactions between various genes involved in atherogenesis. We focus in particular on examples in which unique insights into the human condition have been derived from studies in mice.
Animals↗
Laser and sound scanner for non-contact 3D volume measurement and surface texture analysis.
Non-invasive three-dimensional measurement of volume and analysis of surface texture is desired in various medical applications, particularly wound healing measurements. In this paper we present a PC-based non-contact laser scanner for volume measurements, and a sound scanner that can accurately measure volumes and analyse surface textures. The non-invasive laser and sound sensors, which are lightweight, are mounted inverted on an X-Y table and the sensor heads are held at a distance of 3 cm from the object to be scanned. Volumes of various shapes on different materials, simulating depth profiles and surfaces of wounds, have been measured accurately and surface textures of varying softness have been analysed. The ratios of measured to actual volume range between 0.8 for the sound sensor and 1.1 for the laser sensor. A linear relation between hardness of 50%-20% concentration gelatin gel surfaces and amplitude of reflected sound waves is also observed. The average time per pass of a scan, for a distance of 3 cm, is 4 s and the computation time for measuring volume and reconstruction of a 3D image using ten passes per scan is 1 min. The unique features of this scanner are its speed, portability, accuracy and simple operation as well as its ability to be used on both soft and hard surfaces.
Humans↗