Biomedical subjects
Publications and source records attributed to E A Smith.
Four portable carbon dioxide monitors were assessed by a mobile intensive therapy team during interhospital transfer of critically ill patients. Particular attention was paid to practical considerations such as size, battery life and ease of use. All the monitors performed well in terms of accuracy but problems with size and battery life made some less suitable for use outside hospital.
At 600 kb, the genome of Mycoplasma genitalium is among the smallest known for cellular organisms capable of independent replication. As such, elucidation of the genetic makeup and chromosome architecture of this organism is of considerable interest. We have located 631 markers on the physical map of M. genitalium. The clones have been mapped by hybridizing 20 overlapping cosmid and lambda clones which encompass the entire M. genitalium chromosome to replica filters containing 856 genomic DNA clones. Three hundred fifty-six of these clones represent sequence tag sites, which were previously characterized by database searches. The remaining markers represent clones with an average size of 2.5 kb derived from Sau3A1 partial digestion of genomic DNA. The hybridization data can be divided into three classes: clones which hybridized to only one cosmid; clones which hybridized to two adjacent and overlapping cosmids; and clones which hybridized to several cosmids, which represent repetitive DNA. This rapid approach for placing clones on the physical map has allowed useful comparisons to be made with other bacterial chromosomes, especially that of the closely related organism M. pneumoniae, and has provided insight to the types of events which may have led to the reduction in size of this genome. Future use of these data is discussed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Systemic sclerosis (scleroderma) is a disease of unknown cause whose pathogenesis involves interaction between the vasculature, the immune system, and connective tissue cells. Although specific therapy awaits a better understanding of its pathogenesis, proper management may enhance not only the duration, but the quality of life for most scleroderma patients. Presently, controlled prospective trials of therapeutic agents are lacking. Published reports of drug therapy for skin, kidney, cardiac, pulmonary, and gastrointestinal complications, as well as management of Raynaud's phenomenon, are critically reviewed in this article, and the authors' approach to management of difficult clinical problems is presented.
OBJECTIVE: Systemic sclerosis (scleroderma, SSc) frequently affects the lungs, and interstitial pulmonary fibrosis is one of its major complications. The pathophysiology of SSc lung disease s poorly understood, but recent studies document an inflammatory process resembling that of idiopathic pulmonary fibrosis with increased numbers of activated alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid). We determined levels of 2 potentially important mediators of fibroproliferative repair in BAL fluid from patients with SSc. METHODS: Using Western blot and ELISA techniques we measured levels of platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta in BAL fluid from patients with SSc and healthy controls. The mitogenic effect of these cytokines on SSc lung myofibroblasts was determined by [3H]thymidine incorporation. RESULTS: SSc BAL fluid contains significantly elevated levels of PDGF-AA and PDGF-BB. Where TGF-beta 1 was significantly elevated in SSc lavage fluid, the amount of TGF-beta 2 was significantly less than that observed in normal lavage fluid. Myofibroblasts cultured from SSc lavage fluid exhibited enhanced [3H]thymidine incorporation upon exposure to the growth factors present in SSc BAL fluid: PDGF and TGF-beta 1. SSc lung myofibroblasts pretreated with TGF-beta 1 exhibited an enhanced mitogenic effect upon stimulation by PDGF, due in part to the induction of the PDGF alpha receptor. CONCLUSION: Our studies support a role for PDGF and TGF-beta 1 in the pathogenesis of SSc lung disease.
Extracellular aspartic proteinases have been implicated for some time as virulence factors associated with Candida opportunistic fungal infections. Our present knowledge of the enzymatic properties of these proteinases is rather limited. Information on their substrate specificity is important for understanding their roles in invasive Candida infections. We have isolated aspartic proteinases from each of the three Candida yeasts, Candida albicans, Candida tropicalis, and Candida parapsilosis, and investigated the specificities of these proteinases using a library of synthetic substrates and testing inhibition by pepstatin A. The specificities of these aspartic proteinases are different from those of major human proteinases, including gastric pepsins, renal renin, and cathepsin D. For the peptide substrate, Lys-Pro-Ala-Leu-Phe*Phe(p-NO2)-Arg-Leu, the values of kcat/Km were 2.95 x 10(6) M-1 s-1 for cleavage by Candida albicans proteinase, 1.60 x 10(6) M-1 s-1 for cleavage by Candida tropicalis proteinase, and 0.59 x 10(6) M-1 s-1 for Candida parapsilosis proteinase. Substantial differences in specificity among the Candida yeast proteinases were identified. For example, Candida tropicalis shows large changes in the kcat/Km value depending on the acidobasic character of the residue occupying the P2 position (1.6 x 10(6) M-1 s-1 for Leu, 0.47 x 10(6) M-1 s-1 for Lys, and 0.05 x 10(6) M-1 s-1 for Asp at P2, respectively). Candida parapsilosis by comparison is tolerant of these substitutions at P2 and is highly restrictive at position P4.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitogen-activated protein kinase (MAPK) is activated in many cell types in response to growth factors during the G0-G1 transition in the cell cycle. We investigated the effects of platelet-derived growth factor (PDGF) AA and PDGF BB on activation of MAPK in human dermal fibroblasts, and asked whether its activation correlates with proliferative responses of human fibroblasts to PDGF AA and PDGF BB. Treatment with either PDGF isoform for 20 min resulted in equal phosphorylation of MAPK as visualized by gel shifts in Western blotting with anti-MAPK polyclonal antibody. This finding was confirmed by measurements of MAPK activity in response to increasing doses (2-20 ng/ml) of PDGF AA and PDGF BB in in vitro assays with myelin basic protein as a substrate. PDGF AA was slightly less potent than PDGF BB, but both growth factors induced similar maximal activations. Kinetics of activation were also similar for both isoforms, with maximal induction of MAPK at 10-20 min after growth factor addition followed by a gradual decline to control levels at 1 h. Activation of MAPK by both PDGF isoforms was also confirmed by measuring myelin basis protein phosphorylation in MAPK immunoprecipitates. Thus both PDGF AA and PDGF BB are potent activators of MAPK in human dermal fibroblasts. In contrast, PDGF BB elicited a strong mitogenic response, while PDGF AA had no significant effect on DNA synthesis in human dermal fibroblasts. These data indicate that acute activation of MAPK is not sufficient to stimulate cells to progress through cell cycle. PDGF AA may have other biologic functions or may play a co-stimulatory role in proliferation of human dermal fibroblasts.
A review of 54 consecutive cases of ectopic ureterocele treated at our institution in the last 15 years revealed 4 cases of the cecoureterocele variant. Although the diagnosis of ectopic ureterocele was made preoperatively, the more accurate diagnosis of cecoureterocele was not suggested by preoperative radiographic studies. The cecocele component was disclosed only at endoscopy or during open resection of the ureterocele. A review of the presentation, preoperative assessment, intraoperative management and outcome of each case of unsuspected cecoureterocele suggests that optimal surgical management of the cecocele itself does not require total removal.
Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/myokymia can result from mutations in this gene.
Variations in haematocrit are known to affect the accuracy of reagent strip tests for glucose. We have investigated 10 patients during cardiopulmonary bypass, where intra-operative decreases in haematocrit occur. Whole blood glucose concentrations were measured on five occasions at 30 min intervals during the procedure using the Glucometer II, One Touch II and Reflolux II meters as well as a reference instrument (YSI Model 23 AM). Haematocrits were recorded simultaneously. Overall, for every 10% fall in haematocrit, Glucometer II measurements rose by 22% (r = 0.74, p < 0.00001), One Touch II measurements fell by 3% (r = 0.44, p < 0.002) and the Reflolux II measurements showed no significant variation. The One Touch II showed closer agreement to the reference (mean bias 0.3 mmol.l-1 (95% between +0.86 and -0.26)) than the Reflolux II (bias 1.58 (+3.40 to -0.24)) or the Glucometer II (bias 3.25 (+6.18 to 0.32)). Thus, depending on the meter used, spuriously large intraoperative changes in blood glucose may seem to arise where patient haematocrit varies.
Spinal needles with a pencil-point tip and those of a finer gauge are known to be associated with a lower incidence of postdural puncture headache. This study set out to determine if fine pencil-point needles were acceptably easy to use in routine clinical practice. Two hundred and twelve women undergoing elective Caesarean section were randomly allocated to receive a subarachnoid block using either a 25 G or 27 G Whitacre needle. Factors determining ease of needle use, adequacy of block, incidence of postdural puncture headache, backache and neurological sequelae were assessed. Successful intrathecal injection was achieved in all patients in the 25 G group. Using the 27 G needle, the anaesthetist failed to reach the subarachnoid space in eight patients of which seven subsequently had a successful intrathecal injection with a larger needle. These failures were attributed to excessive needle flexibility which was the only significant difference in ease of use between the 25 G and 27 G needles. In the 25 G group, there was one severe postdural puncture headache which required an epidural blood patch and three mild headaches which resolved spontaneously. There were no postdural puncture headaches in the 27 G group. We conclude that the final choice of needle is a compromise between the ease of use and lower failure rate of the 25 G needle and the, as yet unproven, possibility of a lower incidence of postdural puncture headache with the 27 G needle.
A study was conducted to assess the effect of changes in sample pH and pO2 on the Accutrend, ExacTech Companion, Glucometer II, One Touch II, and Refloflux II blood glucose meters. Venous blood was tonometered after the addition of strong acid or alkali to produce 10 samples with a pH range of 6.54 to 7.73 but with a similar mean pO2 (9.09 +/- 0.096 (SEM) kPa) and pCO2 (5.52 +/- 0.024 kPa). The ExacTech showed a > 15% deviation from the value obtained at pH 7.40 below pH 6.95 and above pH 7.85 (r = 0.69, p = 0.026). Ten further samples were made with a pO2 range of 2.0 to 33.6 kPa but mean pH (7.28 +/- 0.012) and pCO2 (7.98 +/- 0.25 kPa) kept alike. The ExacTech was accurate at pO2 = 11.5 kPa but deviated by > 15% below pO2 = 5.8 kPa and above 22.9 kPa (r = -0.95, p = 0.00002). The Accutrend and One Touch II required a pO2 change of 42 and 45 kPa to achieve the same error (r = -0.82 and r = -0.67 respectively). Thus caution is required in the interpretation of ExacTech glucose measurements in severely acidotic or hypoxic patients.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have isolated and characterized a second aspartic proteinase secreted by the CHUV E-18 strain of Candida parapsilosis. This proteinase is produced at a level corresponding to approximately 25% of the production of the main proteinase described earlier [1]. This minor proteinase has similar molecular weight and pH optimum but differs in the isoelectric point and in the specificity when compared with the major secreted form. The determination of the amino terminal amino acid sequence identified this minor form of Candida parapsilosis aspartic proteinase as a protein which corresponds to the sequence deduced from genomic DNA originally reported as a pseudogene [1]. We conclude that strain CHUV E-18 of Candida parapsilosis expresses and secretes two different aspartic proteinases.
This presentation offers historical and sociolinguistic perspectives regarding the origins of the language used by African-Americans. U.S. descendants of slaves of West and Niger Congo African origin should not be thought of as native speakers of English. To the extent that they have lived in de jure or de facto social isolation from Euro-American English-speaking persons, they have retained a West and Niger Congo African thought process or substratum in the phonology and morphosyntax of their speech. Their mother tongue has been described by several African-American linguists, psychologists, and ethnologists as Ebonics. In a sense, Ebonics refers to the paralinguistic verbal and non-verbal sounds, cues, and gestures that are systematically used in the process of communication by many African-Americans. As one consequence of historical social isolation, African-Americans invariably score poorly on nationally standardized scales of "Standard American" English competence. Therefore, worker notification intended for African-Americans, especially among the blue- and no-collar levels, that does not contain an Afro-centric perspective will likely not prove successful. The linguistic factors, which can severely impede or tremendously enhance the effectiveness of worker notification to these groups, are therefore vital and should not be ignored. Worker notification targeted for limited English-speaking or unlettered populations should include the development of materials and presentations in the language or primary medium best understood by the audience. Based upon research findings on the psycholinguistics of learning modal preference, the development of notification materials that target a learning channel that is audio oral or aural-oral is promoted.
Differences in the responses to growth factors of normal fibroblasts and scleroderma fibroblasts have been demonstrated previously. Because human dermal fibroblasts are heterogeneous populations, whether known differences between papillary and reticular dermal fibroblasts could account for the noted differences between normal and scleroderma fibroblasts was investigated. Papillary dermal fibroblasts were grown from a dermatome section of normal skin from an adult donor. Reticular dermal fibroblasts were cultured from punch biopsy specimens taken from the same location. In vitro, papillary dermal fibroblasts proliferated more rapidly, had a higher mitotic index and reached greater density at confluence, confirming previous observations. The reticular dermal fibroblasts were more dendritic. Reticular dermal fibroblasts had higher rates of tritiated thymidine uptake and larger increases in mitotic index in response to isoforms of platelet-derived growth factor (PDGF). The characteristic response of scleroderma fibroblasts, potentiation of the mitogenicity of PDGF AA by transforming growth factor-beta (TGF-beta), was not observed in either cell type. Therefore, the phenotypic characteristics of scleroderma fibroblasts cannot be explained by an unusual admixture of papillary and reticular fibroblasts.