Showing papers by "University of Texas Medical Branch published in 1994"
TL;DR: Six patients from northern Minnesota and Wisconsin with a febrile illness accompanied by granulocytic cytoplasmic morulae suggestive of ehrlichial infection were identified and were shown to be infected by an Ehrlichia species never previously reported to infect humans.
Abstract: Six patients from northern Minnesota and Wisconsin with a febrile illness accompanied by granulocytic cytoplasmic morulae suggestive of ehrlichial infection were identified. Two patients died, and splenic granulocytes of one patient contained cytoplasmic vacuoles with organisms ultrastructurally characteristic of ehrlichiae. From one patient, a 1.5-kb DNA product was amplified by PCR with universal eubacterial primers of 16S rDNA. Analysis of the nucleotide sequence of the amplified product revealed 99.9 and 99.8% similarities with E. phagocytophila and E. equi, respectively, neither of which has previously been known to infect humans. From the variable regions of the determined sequence, a forward primer specific for three organisms (human granulocytic ehrlichia, E. phagocytophila, and E. equi) and a reverse primer for these ehrlichiae and E. platys were designed. By nested PCR with amplification by the universal primers and then reamplification with the specific primers described above, the expected 919-bp product was generated from the blood of the index patient and three additional patients. Blood from these four patients and two more patients with granulocytic morulae contained DNA which was amplified by nested PCR involving a combination of a universal primer and the human granulocytic ehrlichia-E. phagocytophila-E. equi-E. platys group-specific primer. This apparently vector-borne human granulocytic ehrlichia has only 92.5% 16S rDNA homology with E. chaffeensis. Nested PCR with group-specific primers did not amplify E. chaffeensis DNA, and E. chaffeensis-specific primers did not amplify DNAs of the human granulocytic ehrlichia. Thus, six patients were shown to be infected by an Ehrlichia species never previously reported to infect humans.
962 citations
TL;DR: The RAD51 gene of Saccharomyces cerevisiae is required for genetic recombination and DNA double-strand break repair and it is demonstrated that RAD51 protein pairs circular viral single-stranded DNA from phi X 174 or M13 with its respective homologous linear double-Stranded form, indicating that RAD 51 can catalyze strand exchange.
Abstract: The RAD51 gene of Saccharomyces cerevisiae is required for genetic recombination and DNA double-strand break repair. Here it is demonstrated that RAD51 protein pairs circular viral single-stranded DNA from phi X 174 or M13 with its respective homologous linear double-stranded form. The product of synapsis between these DNA partners is further processed by RAD51 to yield nicked circular duplex DNA, which indicates that RAD51 can catalyze strand exchange. The pairing and strand exchange reaction requires adenosine triphosphate, a result consistent with the presence of a DNA-dependent adenosine triphosphatase activity in RAD51 protein. Thus, RAD51 is a eukaryotic recombination protein that can catalyze the strand exchange reaction.
866 citations
TL;DR: The treatment of bipolar illness could be enhanced by public health efforts to promote early diagnosis and treatment; ensuring adequate trials of mood-stabilizers for patients with frequent recurrences; further research on bipolar disorder with prominent anxiety symptoms; and improved access to mental health care.
853 citations
TL;DR: The results of the present study suggest that the animal model exhibits neuropathic pain behaviors including ongoing pain, heat hyperalgesia, mechanical allodynia and cold allodynian and that this model represents a model for sympathetically maintained pain.
Abstract: Previous studies by our laboratory established a rat model of neuropathic pain which displayed long-lasting heat hyperalgesia and mechanical allodynia that are sympathetically maintained The present study was undertaken to extend our earlier findings by examining additional behavioral signs of ongoing pain and cold allodynia in our animal model and testing their sympathetic dependency Neuropathic surgery was done by tightly ligating the L5 and L6 segmental spinal nerves of rats unilaterally In addition to the behavioral signs of heat hyperalgesia and mechanical allodynia observed before, these rats displayed signs of ongoing pain (lasting at least 10 weeks) and cold allodynia (lasting at least 16 weeks) These behaviors were reduced markedly after surgical lumbar sympathectomy The results of the present study, together with the previous study, suggest that our animal model exhibits neuropathic pain behaviors including ongoing pain, heat hyperalgesia, mechanical allodynia and cold allodynia Since all of these behavioral signs are sympathetically maintained, our model represents a model for sympathetically maintained pain
759 citations
TL;DR: Two ternary complexes of rat DNA polymerase beta, a DNA template-primer, and dideoxycytidine triphosphate have been determined at 2.9 A and 3.6 A resolution, suggesting that the polymerase-DNA-ddCTP interactions are not affected by crystal packing forces.
Abstract: Two ternary complexes of rat DNA polymerase beta (pol beta), a DNA template-primer, and dideoxycytidine triphosphate (ddCTP) have been determined at 2.9 A and 3.6 A resolution, respectively. ddCTP is the triphosphate of dideoxycytidine (ddC), a nucleoside analog that targets the reverse transcriptase of human immunodeficiency virus (HIV) and is at present used to treat AIDS. Although crystals of the two complexes belong to different space groups, the structures are similar, suggesting that the polymerase-DNA-ddCTP interactions are not affected by crystal packing forces. In the pol beta active site, the attacking 3'-OH of the elongating primer, the ddCTP phosphates, and two Mg2+ ions are all clustered around Asp190, Asp192, and Asp256. Two of these residues, Asp190 and Asp256, are present in the amino acid sequences of all polymerases so far studied and are also spatially similar in the four polymerases--the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, T7 RNA polymerase, and rat DNA pol beta--whose crystal structures are now known. A two-metal ion mechanism is described for the nucleotidyl transfer reaction and may apply to all polymerases. In the ternary complex structures analyzed, pol beta binds to the DNA template-primer in a different manner from that recently proposed for other polymerase-DNA models.
728 citations
TL;DR: The report that follows defines wound, acute wound, chronic wound, healing and forms of healing, wound assessment, wound extent, wound burden, and wound severity, broadly applicable to all wounds.
Abstract: Background: Chronic wounds represent a worldwide problem. For laboratory and clinical research to adequately address this problem, a common language needs to exist. Observation: This language should include a system of wound classification, a lexicon of wound descriptors, and a description of the processes that are likely to affect wound healing and wound healing end points. Conclusions: The report that follows defines wound, acute wound, chronic wound, healing and forms of healing, wound assessment, wound extent, wound burden, and wound severity. The utility of these definitions is demonstrated as they relate to the healing of a skin wound, but these definitions are broadly applicable to all wounds. (Arch Dermatol. 1994;130:489-493)
660 citations
TL;DR: Gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCIDs-like phenotype.
Abstract: Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.
637 citations
TL;DR: The report that follows defines wound, acute wound, chronic wound, healing and forms of healing, wound assessment, wound extent, wound burden, and wound severity, broadly applicable to all wounds.
Abstract: Chronic wounds represent a worldwide problem. For laboratory and clinical research to adequately address this problem, a common language needs to exist. This language should include a system of wound classification, a lexicon of wound descriptors, and a description of the processes that are likely to affect wound healing and would healing end points. The report that follows defines wound, acute wound, chronic wound, healing and forms of healing, wound assessment, wound extent, wound burden, and wound severity. The utility of these definitions is demonstrated as they relate to the healing of a skin wound, but these definitions are broadly applicable to all wounds.
574 citations
TL;DR: All 12 patients have been infected with a granulocytic Ehrlichia species, reflecting a recently described new disease entity, and early detection and treatment with tetracycline drugs appear to offer the best chance for complete recovery.
Abstract: Objective. —To characterize the clinical presentation and course, laboratory findings, and treatment outcome of 12 patients with human granulocytic ehrlichiosis. Setting. —The 12 patients were male, ranged in age from 29 to 91 years, and contracted their illness in Wisconsin or Minnesota. Methods. —Cases were recognized by the presence of intracytoplasmic inclusions (morulae) in peripheral neutrophils of patients presenting with temperature of 38.5°C or higher, chills, severe headache, and myalgias. All patients had a complete blood cell count and blood chemistry profile. Blood smears were examined by light microscopy. All available paired serum samples were analyzed for presence of indirect fluorescent antibodies againstEhrlichia chaffeensis, Ehrlichia phagocytophila, andEhrlichia equi. Blood samples from 12 patients were subjected to polymerase chain reaction analysis using primers specific for theE phagocytophila/E equigroup, primers that include the agent identified in our patients, as well asE chaffeensis. Results. —Varying combinations of leukopenia, anemia, and thrombocytopenia were found in all but one patient. All 12 patients demonstrated morulae in the cytoplasm of neutrophils, but not in mononuclear white blood cells. Serum assays failed to detect antibodies againstE chaffeensis, but eight of 10 patients and seven of 10 patients tested had antibody titers of 1:80 or more forE phagocytophilaandE equi, respectively. Polymerase chain reaction products obtained with primers forE phagocytophila, E equi, and the granulocytotropicEhrlichiarevealed that seven patients were infected with the same agent. The results of serological assays or polymerase chain reaction strongly suggest that all 12 patients were infected byE phagocytophila, E equi, or a closely relatedEhrlichiaspecies. Two of the 12 patients died. The other 10 patients improved rapidly with oral doxycycline treatment. Conclusions. —We believe that all 12 patients have been infected with a granulocyticEhrlichiaspecies, reflecting a recently described new disease entity. The infective organism appears to be closely related toE phagocytophilaandE equi. The geographic domain of human granulocytic ehrlichiosis is currently unknown. This novel granulocyticEhrlichiaspecies is capable of causing fatal infections in humans. Early detection and treatment with tetracycline drugs appear to offer the best chance for complete recovery. (JAMA. 1994;272:212-218)
519 citations
TL;DR: Data indicate that the residue in position 104 helps to define the geometry of the hydrophobic substrate-binding site, and may also influence activity by interacting with residues directly involved in substrate binding.
Abstract: Glutathione S-transferase P1-1 isoforms, differing in a single amino acid residue (Ile104 or Val104), have been previously identified in human placenta [Ahmad, H., Wilson, D. E., Fritz, R. R., Singh, S. V., Medh, R. D., Nagle, G. T., Awasthi, Y. C. & Kurosky, A. (1990) Arch. Biochem. Biophys. 278, 398-408]. In the present report, the enzymic properties of these two proteins are compared. [I104]glutathione S-transferase P1-1 has been expressed from its cDNA in Escherichia coli and purified to homogeneity by affinity chromatography; the cDNA has been mutated to replace Ile104 by Val104, and [V104]glutathione S-transferase P1-1 was expressed and isolated as described for [I104]glutathione S-transferase P1-1. The two enzymes differed in their specific activity and affinity for electrophilic substrates (KM values for 1-chloro-2,4-dinitrobenzene were 0.8 mM and 3.0 mM for [I-104]glutathione S-transferase P1-1 and [V-104]glutathione S-transferase P1-1, respectively), but were identical in their affinity for glutathione. In addition, the two enzymes were distinguishable by their heat stability, with half-lives at 45 degrees C of 19 min and 51 min, respectively. The resistance to heat denaturation was differentially modulated by the presence of substrates. These data, in conjunction with molecular modeling, indicate that the residue in position 104 helps to define the geometry of the hydrophobic substrate-binding site, and may also influence activity by interacting with residues directly involved in substrate binding.
TL;DR: The two invariant aspartates found in all polymerase sequences and implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicating that the polymerases have maintained, or possibly re-evolved, a common nucleotidyl transfer mechanism.
Abstract: Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom resolution, respectively. The 31-kilodalton domain is composed of fingers, palm, and thumb subdomains arranged to form a DNA binding channel reminiscent of the polymerase domains of the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, and bacteriophage T7 RNA polymerase. The amino-terminal 8-kilodalton domain is attached to the fingers subdomain by a flexible hinge. The two invariant aspartates found in all polymerase sequences and implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicating that the polymerases have maintained, or possibly re-evolved, a common nucleotidyl transfer mechanism. The location of Mn2+ and deoxyadenosine triphosphate in pol beta confirms the role of the invariant aspartates in metal ion and deoxynucleoside triphosphate binding.
TL;DR: Books and internet are the recommended media to help you improving your quality and performance.
Abstract: Inevitably, reading is one of the requirements to be undergone. To improve the performance and quality, someone needs to have something new every day. It will suggest you to have more inspirations, then. However, the needs of inspirations will make you searching for some sources. Even from the other people experience, internet, and many books. Books and internet are the recommended media to help you improving your quality and performance.
TL;DR: Whereas RAD6 has no affinity for DNA, RAD18 binds single-stranded DNA, and association of RAD6 with RAD18 could provide a means for targeting RAD6 to damage-containing DNA regions, where the RAD6 ubiquitin-conjugating function could modulate the activity of a stalled DNA replication machinery.
Abstract: The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme that is required for postreplication repair of UV-damaged DNA, DNA damage induced mutagenesis, sporulation, and amino-end rule protein degradation. RAD6 interacts physically with the UBR1 gene product in carrying out the multiubiquitination of amino-end rule proteolytic substrates. In mediating postreplication repair, it has remained unclear whether RAD6 acts in a pleiotropic manner distal from the site of DNA damage or is targeted to the damage site via interaction with another repair component. Here, we show that RAD6 forms a specific complex with the product of the DNA repair gene RAD18. The biological significance of this interaction is attested by the observation that overproduction of the rad6 Ala-88 mutant protein, which lacks ubiquitin-conjugating activity but retains the ability to interact with RAD18 protein, confers a high level of UV sensitivity on wild-type RAD+ cells that can be corrected by the concomitant overexpression of RAD18. We demonstrate that whereas RAD6 has no affinity for DNA, RAD18 binds single-stranded DNA. Thus, association of RAD6 with RAD18 could provide a means for targeting RAD6 to damage-containing DNA regions, where the RAD6 ubiquitin-conjugating function could modulate the activity of a stalled DNA replication machinery. We also show that RAD6 forms separate complexes with RAD18 and with UBR1, and the extremely conserved amino terminus of RAD6 that is required for complex formation with UBR1 is dispensable for complex formation with RAD18.
Book•
07 Sep 1994TL;DR: Information is provided for evaluating and using the Epidemiological Mental Health Literature with Multicultural Groups Using Culturally Biased Instruments Using Cultural Variables in the Diagnostic and Statistical Manual of Mental Disorders.
Abstract: Minority, Multicultural, Race, and Ethnicity Concepts General Guidelines for the Assessment and Treatment of Multicultural Groups Guidelines for the Assessment and Treatment of African American Clients Guidelines for the Assessment and Treatment of Hispanic Clients Guidelines for the Assessment and Treatment of Asian Clients Guidelines for the Assessment and Treatment of American Indian Clients Guidelines for the Prevention of Attrition of African American, American Indian, Asian and Hispanic Clients Guidelines for Evaluating and Using the Epidemiological Mental Health Literature with Multicultural Groups Using Culturally Biased Instruments Using Cultural Variables in the Diagnostic and Statistical Manual of Mental Disorders
TL;DR: Apoptosis and necrosis are two distinctly different forms of cell death, and both occur in the human heart as discussed by the authors, but unlike necrosis, apoptosis is not associated with inflammation for two reasons: the apoptotic cell does not swell or rupture before it is engulfed by either a macrophage or even a neighboring like cell.
Abstract: Apoptosis and necrosis are two distinctly different forms of cell death, and both occur in the human heart. In contrast to necrosis, apoptosis is not associated with inflammation for two reasons. First, the apoptotic cell does not swell or rupture before it is engulfed by either a macrophage or even a neighboring like cell. Second, the phagocytosis occurs with unusual rapidity. Apoptosis, also thought of as cell suicide, is a tidy way of removing cells no longer useful, in essence a form of selective deletion. These features make apoptosis a valuable component of morphogenesis, mediation of hormonal and immunologic responses, and the homeostatic balance between hypertrophy and atrophy or involution. In the human heart apoptosis has been found in the sinus node of patients with the long QT syndrome. It most likely participates in the important postnatal morphogenesis of the sinus node, AV node, and His bundle. Apoptosis may also participate in the genesis and pathophysiology of cardiomyopathy, paroxysmal arrhythmias, or conduction disturbances (some of which may be responsible for sudden death), focal fibromuscular dysplasia of small coronary arteries, hereditary medial degeneration of the tunica media of coronary arteries, and arrhythmogenic right ventricular dysplasia. The possible role apoptosis in numerous other changes in the human heart, among them the pathogenesis of atherosclerosis and mechanisms of aging in the myocardium, merits future investigation.
Journal Article•
TL;DR: The results suggest that resistance to epipodophyllotoxins in MCF7/VP cells is multifactorial, involving a reduction in intracellular drug concentration, possibly as a consequence of MRP overexpression, and an altered DNA topoisomerase II drug sensitivity.
Abstract: A human breast cancer cell line (MCF7/WT) was selected for resistance to etoposide (VP-16) by stepwise exposure to 2-fold increasing concentrations of this agent. The resulting cell line (MCF7/VP) was 28-, 21-, and 9-fold resistant to VP-16, VM-26, and doxorubicin, respectively. MCF7/VP cells also exhibited low-level cross-resistance to 4'-(9-acridinylamino)-methanesulfon-m-anisidide, mitoxantrone, and vincristine and no cross-resistance to genistein and camptothecin. Furthermore, these cells were collaterally sensitive to the alkylating agents melphalan and chlorambucil. DNA topoisomerase II levels were similar in both wild-type MCF7/WT and drug-resistant MCF7/VP cells. In contrast, topoisomerase II from MCF7/VP cells appeared to be 7-fold less sensitive to drug-induced cleavable complex formation in whole cells and 3-fold less sensitive in nuclear extracts than topoisomerase II from MCF7/WT cells. Although this suggested that the resistant cells may contain a qualitatively altered topoisomerase II, no mutations were detected in either the ATP-binding nor the putative breakage/resealing regions of either DNA topoisomerase II alpha or II beta. In addition, the steady-state intracellular VP-16 concentration was reduced by 2-fold in the resistant cells, in the absence of detectable mdr1/P-gp expression and without any change in drug efflux. In contrast, expression of the gene encoding the MRP was increased at least 10-fold in resistant MCF7/VP cells as compared to sensitive MCF7/WT cells. These results suggest that resistance to epipodophyllotoxins in MCF7/VP cells is multifactorial, involving a reduction in intracellular drug concentration, possibly as a consequence of MRP overexpression, and an altered DNA topoisomerase II drug sensitivity.
TL;DR: Initial tumor size and neck disease are the only predictors of distant metastases and Lung is the most common DM site, making chest x‐ray the most effective DM screen.
Abstract: Distant metastases (DMs) occurred in 83 (11.4%) of 727 retrospectively studied head and neck cancer patients. Primary tumor location and initial treatment did not influence DM development; larger primaries (P < .04) or more extensive neck disease (P < .007) more often caused DMs. Initial diagnosis to DMs averaged 11.7 months (range, 0 to 60 months), with 84% diagnosed within 24 months. With the exception of laryngeal primaries, no facet of tumor, host, or initial treatment influenced where or how rapidly DMs developed. Lung was the most common DM site (83.4%), then bone (31.1%) and liver (6.0%). Survival with DMs averaged 4.3 months (range, 1 day to 2.7 years); 86.7% died within 1 year. This report yields the following conclusions: 1. Initial tumor size and neck disease are the only predictors of DMs. 2. DMs usually occur within 2 years of the initial diagnosis. 3. Lung is the most common DM site, making chest x-ray the most effective DM screen. 4. Survival with DMs is usually less than a year.
TL;DR: The rapid metabolic inactivation of mutagenic flavonoids catalyzed by catechol-O-methyltransferase may be a major reason for the lack of their carcinogenic activities in vivo.
TL;DR: GST isoenzymes present in human tissues are dimers of subunits belonging to three distinct gene families namely alpha, mu and pi as discussed by the authors, and only the subunits within each class hybridize to give active dimers.
TL;DR: Reassurance seeking served as a vulnerability factor for the contagion effect: high-but not low-reassurance-seeking roommates of depressed target students became more depressed themselves over the course of the 3-week study.
Abstract: This study prospectively examined the phenomenon of contagious depression in 96 pairs of college roommates during 2 assessment sessions separated by 3 weeks. Depression, anxiety, negative and positive affect, negative life stress, and reassurance seeking were assessed. Consistent with prediction, roommates of depressed target students became more depressed themselves over the course of the 3-week study. The effect persisted when baseline levels of roommate depression and roommate negative life events were controlled. Furthermore, these findings were specific to depressed symptoms. Finally, as predicted, reassurance seeking served as a vulnerability factor for the contagion effect: High-but not low-reassurance-seeking roommates of depressed target students became more depressed themselves. However, the moderating effects of reassurance seeking were not specific to depressed symptoms.
TL;DR: The inhibitory action of L -arginine and 8-bromo-cyclic guanosine monophosphate was considerably lower during delivery and post partum, indicating that the nitric oxide system may contribute to the maintenance of uterine quiescence during pregnancy, when progesterone levels are elevated, but not during delivery.
TL;DR: It is concluded that highly trained male endurance runners use more fat as a fuel during low-intensity exercise than do untrained healthy men despite similar rates of lipolysis and FFA uptake from plasma.
Abstract: Whole body lipid kinetics were evaluated during basal resting conditions, 4 h of treadmill exercise eliciting an oxygen uptake of 20 ml.kg-1.min-1, and 1 h of recovery in five untrained and five endurance-trained men. Glycerol and free fatty acid (FFA) rate of appearance (Ra) values in plasma were determined by infusing [2H5]glycerol and [1-13C]palmitate, respectively, and lipid oxidation was determined by indirect calorimetry. The lipolytic response to 4 h of exercise, expressed as the average glycerol and FFA Ra values, was similar in both trained (9.85 +/- 1.02 and 24.64 +/- 3.76 mumol.kg-1.min-1, respectively) and untrained subjects (11.29 +/- 0.99 and 24.13 +/- 0.39 mumol.kg-1.min-1, respectively). However, mean triglyceride oxidation was greater during exercise in the trained than in the untrained group (7.51 +/- 0.26 and 5.67 +/- 0.51 mumol.kg-1.min-1, respectively; P < 0.001). During recovery, glycerol and FFA Ra values decreased more rapidly in trained than in untrained subjects. We conclude that highly trained male endurance runners use more fat as a fuel during low-intensity exercise than do untrained healthy men despite similar rates of lipolysis and FFA uptake from plasma. Therefore, the increase in fat oxidation must be related to an increased percentage of FFA uptake oxidized, a greater contribution from intramuscular triglyceride stores, or both. Additionally, lipid kinetics return to baseline more rapidly in trained than in untrained subjects after completing an exercise bout of the same absolute intensity.
TL;DR: It is imperative that the surgeon identify the elderly patient who is at increased risk for complications, and specific consideration must be given to proper management of fluid and electrolyte replacement, respiratory management to prevent atelectasis and pneumonia, and monitoring for possible cardiac complications.
TL;DR: Levels of cytokines found in these chronic wounds are much lower than those reported from acute wounds, and may help to explain the differences reported in recent wound healing trials with exogenous cytokines.
Abstract: ObjectiveThis study objectively characterized the microenvironment of indolent, chronic wounds by developing a method by which minute quantities of cytokines could be extracted from chronic wounds and separately identified.Summary Background DataRecombinant DNA technology and the ability to clone co
TL;DR: The purify RAD25 protein from S. cerevisiae is purified and shows that it contains single-stranded DNA-dependent ATPase and DNA helicase activities, indicating a direct and essential role of RAD25 in RNA polymerase II transcription.
Abstract: The RAD25 gene of Saccharomyces cerevisiae functions in nucleotide excision repair of ultraviolet-damaged DNA and is also required for cell viability. The RAD25 protein shows remarkable homology to the protein encoded by the human nucleotide-excision-repair gene XPB (ERCC3), mutations in which cause the cancer-prone disease xeroderma pigmentosum and also Cockayne's syndrome. Here we purify RAD25 protein from S. cerevisiae and show that it contains single-stranded DNA-dependent ATPase and DNA helicase activities. Extract from the conditional lethal mutant rad25-ts24 exhibits a thermolabile transcriptional defect which can be corrected by the addition of RAD25 protein, indicating a direct and essential role of RAD25 in RNA polymerase II transcription. The protein encoded by the rad25799am allele is defective in DNA repair but is proficient in RNA polymerase II transcription, indicating that RAD25 DNA-repair activity is separable from its transcription function. The rad25 Arg-392 encoded product, which contains a mutation in the ATP-binding motif, is defective in RNA polymerase II transcription, suggesting that the RAD25-encoded DNA helicase functions in DNA duplex opening during transcription initiation.
Journal Article•
TL;DR: A recent review suggests zinc deficiency is common among populations of developing countries, particularly those that are deficient in iron.
TL;DR: Extensive animal model data support the hypothesis that ventilator-driven alveolar overdistention can induce significant parenchymal lung injury, and avoidance of alveolars overdistsention through pressure or volume limitation has significant support based on animal models and computer simulation.
Abstract: Objective. —To evaluate the potential efficacy of pressure limitation with permissive hypercapnia in the treatment of acute respiratory failure/adult respiratory distress syndrome on the basis of current theories of ventilator-induced lung injury, potential complications of systemic hypercarbia, and available human outcome studies. Data Sources. —Articles were identified through MEDLINE, reference citations of published data, and consultation with authorities in their respective fields. Study Selection. —Animal model experimentation and human clinical trials were selected on the basis of whether they addressed the questions of pressure limitation with or without hypercapnia, the pathophysiologic effects of hypercapnia, or the concept of ventilator-induced parenchymal lung injury. Frequently cited references were preferentially included. Data Extraction. —Data were analyzed with particular emphasis on obtaining the following variables from the clinical studies: peak inspiratory pressures, tidal volumes, minute ventilation, and Pco2. Quantitative aspects of respiratory physiology were used to analyze the theoretical effects of permissive hypercapnia on ventilatory requirements in normal and injured lungs. Data Synthesis. —Extensive animal model data support the hypothesis that ventilator-driven alveolar overdistention can induce significant parenchymal lung injury. The heterogeneous nature of lung injury in adult respiratory distress syndrome, with its small physiologic lung volume, may render the lung susceptible to this type of injury through the use of conventional tidal volumes (10 to 15 mL/kg). Permissive hypercapnia is an approach whereby alveolar overdistention is minimized through either pressure or volume limitation, and the potential deleterious consequences of respiratory acidosis are accepted. Uncontrolled human trials of explicit or implicit permissive hypercapnia have demonstrated improved survival in comparison with models of predictive mortality. Conclusions. —Avoidance of alveolar overdistention through pressure or volume limitation has significant support based on animal models and computer simulation. Deleterious effects of the associated hypercarbia in severe lung injury do not appear to be a significant limiting factor in preliminary human clinical trials. Although current uncontrolled studies suggest benefit, controlled trials are urgently needed to confirm these findings before adoption of the treatment can be endorsed. (JAMA. 1994;272:957-962)
TL;DR: Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated and both groups receiving rhGH showed a significant reduction in donor site healing time compared with placebo.
Abstract: OBJECTIVE: Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated. SUMMARY BACKGROUND DATA: Growth hormone has been shown to reduce wound healing times in burned pediatric patients. Through genetic engineering, several different forms have been synthesized; however, not all are marketed currently. Two forms of growth hormone were used in these studies, Protropin (Genentech, Inc., San Francisco, CA), a commercially available product that possesses a N-terminal methionine residue not found in the second form Nutropin (Genentech, Inc., San Francisco, CA), which, as yet, is not commercially available. Through the use of recombinant human growth hormone, rapid wound healing may reduce the hypermetabolic period, the risk of infection, and accelerate the healing of donor sites used for grafting onto burned areas. The two structurally different forms of growth hormone were tested for their efficacy in healing donor sites in severely burned children. METHODS: Forty-six children, with a > 40% total body surface area and > 20% total body surface area full-thickness burn were entered in a double-blind, randomized study to receive rhGH within 8 days of injury. Twenty received (0.2 mg/kg/day) Nutropin or placebo by subcutaneous or intramuscular injection beginning on the morning of the initial excision. Eighteen patients who failed the entry criteria for receiving Nutropin received Protropin therapeutically (0.2 mg/kg/day). Donor sites were harvested at 0.006 to 0.010 inches in depth and dressed with Scarlet Red impregnated fine mesh gauze (Sherwood Medical, St. Louis, MO). The initial donor site healing time, in days, was reached when the gauze could be removed without any trauma to the healed site. RESULTS: Donor sites in patients receiving Nutropin (n = 20) or Protropin (n = 18) healed at 6.8 +/- 1.5 and 6.0 +/- 1.5 (mean +/- SD) days, respectively, whereas those receiving placebo (n = 26) had a first donor site healing time of 8.5 +/- 2.3 days. Both groups receiving rhGH showed a significant reduction in donor site healing time compared with placebo at p < 0.01. When subgroups were compared, no difference in healing times could be shown with regards to age or time of admission after injury. CONCLUSION: Our results indicate that both forms of rhGH are effective in reducing donor site healing time compared with placebo and suggest that accelerating wound healing is of clinical benefit because the patients' own skin becomes rapidly available for harvest and autografting. With this increase in the rate of wound healing, the total length of hospital stay can be reduced by more than 25%.