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Biomedical subjects

D L Smith

Publications and source records attributed to D L Smith.

At least 235 records · Page 13Linked to original sources

Cardiovascular responses to sustained maximal isometric contractions of the finger flexors.

This study investigated cardiovascular responses to 2 min sustained submaximal (20% MVC) and maximal (100% MVC) voluntary isometric contractions of the finger flexors in healthy young women. Cardiovascular variables investigated were: heart rate (fc), mean arterial pressure (Pa), and stroke volume (SV). Doppler echocardiography was used to estimate SV from measures of aortic diameter (AD) and time-velocity integrals. Preliminary studies indicated that AD did not change significantly after 2 min sustained 100% MVC. Therefore, pre-exercise AD values were used to calculate SV before, during and after exercise. During the 2-min 100% MVC period, fc and Pa increased significantly during the first 30 s of contraction. fc then remained constant during the remainder of the 2-min contraction period, while Pa continued to rise. SV did not change significantly during the 100% MVC task but increased significantly during recovery from sustained 100% MVC. The data suggest that the magnitude of cardiovascular responses to isometric exercise is dependent on the specific task performed, and that there is a different pattern of response for fc, Pa, and SV during 20% and 100% MVC tasks. Unlike fc and Pa, SV did not change significantly during isometric exercise, but increased significantly after sustained 100% MVC.

Adult↗

Primary structure of rabbit lens alpha-crystallins.

The primary structure and posttranslational modifications of rabbit lens alpha-crystallins were examined using electrospray ionization mass spectrometry to determine the molecular weights of the intact proteins and fast atom bombardment mass spectrometry to analyze proteolytic digests of the alpha A- and alpha B-crystallins. The previously determined primary structure of alpha A-crystallin was confirmed. Posttranslational modifications detected included one phosphorylation site and the presence of a truncated form minus the five C-terminal residues. The previously undetermined amino acid sequence of rabbit alpha B-crystallin was determined to be the same as the bovine alpha B-crystallin sequence except at three residues: Thr 40, Thr 132, and Pro 153. Rabbit alpha B-crystallin showed evidence of phosphorylation at the same three sites as bovine alpha B-crystallin. The molecular weights of the intact proteins indicated that any one molecule had a maximum of two phosphorylations. Also, there was a truncated form which did not include the five C-terminal residues.

Amino Acid Sequence↗

Biologically active acetogenins from stem bark of Asimina triloba.

In continuing our research with cytotoxic and pesticidal components from the stem bark of the North American paw paw, Asimina triloba, the novel cytotoxic monotetrahydrofuran Annonaceous acetogenins, cis- and trans-annonacin-A-one, cis- and trans-gigantetrocinone and cis-isoannonacin, in addition to the known compounds, trans-isoannonacin and squamolone, have been identified. Brine shrimp lethality testing was used to direct the fractionation. The structures were elucidated by spectral analysis and/or chemical synthesis. These acetogenins have potent cytotoxicities against the human tumour cell lines of A-549 (lung carcinoma), MCF-7 (breast carcinoma) and HT-29 (colon adenocarcinoma).

Animals↗

Epidemiology of Pseudomonas aeruginosa infection in cystic fibrosis and the use of strain genotyping.

We describe a study of the epidemiology of Pseudomonas aeruginosa (PA) infection in a group of adults with cystic fibrosis who attended a week-long summer camp in the U.K. Sputum samples were collected from 17 patients at the beginning and at the end of the holiday period. Examination of previous sputum samples had identified 11 patients who were chronically colonised with PA. They shared accommodation during the holiday. The sputum samples from these 11 patients were analysed so as to identify the strains of PA by their genotypic characters. All patients were colonised by unique strains before the beginning of the holiday, with the exception of two pairs of patients whose isolates were indistinguishable. After the holiday, eight of the 11 patients harboured strains of the same genotype as was found in their pre-holiday specimens. In three patients, a strain present post-holiday was different from that found in the pre-holiday specimen. In addition, in the case of one patient, two different genotypes were found in the pre-holiday specimen, only one of which was present after the holiday. Evidence of cross-infection of PA during the holiday was not found. Even so, evidence of person-to-person transmission of PA both within the hospital environment and through social contact is presented and discussed.

Adolescent↗

A large Q fever outbreak in the West Midlands: clinical aspects.

In the spring of 1989 the largest outbreak of acute Q fever recorded in the United Kingdom occurred in Solihull and surrounding areas of the West Midlands. The diagnosis was confirmed in 147 people, mainly males of working age. Windborne spread from farmland to the south of the urban area was the most likely route of infection. Fever was the commonest symptom, seen in 101/102 (99%) cases, followed by weight loss reported by 83/101 (82%). Headache, often severe, was experienced by 69/101 (68%). The commonest respiratory symptom was breathlessness, 65/102 (64%), followed by cough, 52/102 (51%), and chest pain, 46/102 (45%). Neurological features, seen in 23% of cases, were more prominent in this outbreak than is commonly recognized. Persisting ill health 6 months following the acute episode not due to chronic Q fever was also a prominent feature of this largely urban outbreak.

Adolescent↗

30-, 31-, and 32-hydroxybullatacinones: bioactive terminally hydroxylated annonaceous acetogenins from Annona bullata.

From Annona bullata, three more pairs of new ketolactone Annonaceous acetogenins were isolated by bioactivity-directed isolation. They are hydroxylated adjacent bistetrahydrofuran (THF) acetogenins and are named (2,4-cis and trans)-32-hydroxybullatacinone (1 and 2), (2,4-cis and trans)-31-hydroxybullatacinone (3 and 4), and (2,4-cis and trans)-30-hydroxybullatacinone (5 and 6). The structures were elucidated by analysis of the 1H- and 13C-nmr spectra of 1-6 and their acetates and the ms of their tri-trimethylsilyl (TMSi) derivatives as compared with bullatacinone [7]. This is the first time that Annonaceous acetogenins with OH groups at successive positions near the end of the aliphatic chain have been reported. All of the new compounds showed potent activities in the brine shrimp lethality test and against human solid tumor cells in culture, with selectivities exhibited especially toward the colon cancer cell line (HT-29).

Animals↗

Diagnosis of myocardial contusion.

From July 1988 to July 1990, 159 consecutive cases of major blunt chest injury were evaluated prospectively for myocardial contusion with serial electrocardiographic monitoring, cardiac isoenzyme studies, and two-dimensional echocardiography. One hundred and forty-seven cases in the series were assessable; 97 of the patients were male, and 50 were female. They ranged in age from 2 to 97 years (average, 38.5 years). There were five deaths, none of cardiac origin. Total lactate dehydrogenase (LDH) values were elevated in 115 patients (78%); total creatine phosphokinase (CPK) values were elevated in 100 (68%). Cardiac isoenzyme patterns were consistent with myocardial contusion in 18 patients (12%). Seventy-five patients had abnormal electrocardiograms, and 10 of these had ectopic rhythms. Two-dimensional echocardiograms were completed in 58 cases; 12 of these (21%) were abnormal. Nineteen patients (25%) with abnormal rhythms had elevated LDH values, and 26 (35%) had elevated CPK values. One patient (10%) with ectopy had an abnormal echocardiogram. Two patients (11%) with abnormal isoenzyme patterns experienced dysrhythmias. Costs for hospitalization and studies amounted to $1,886 per patient. Given the poor predictive value of laboratory testing in patients with significant (ie, symptomatic) cardiac contusion, observation alone with electrocardiographic monitoring and treatment of symptomatic dysrhythmias is an adequate and cost-conscious treatment.

Adolescent↗

A versatile system for detecting transposition in Arabidopsis.

The maize transposable element Activator (Ac) has been shown to be active in a number of dicots, including Arabidopsis thaliana, whose small genome and short generation time have favored its wide adoption as a model organism for molecular genetic approaches to plant physiology and development. Using the Ac element and several bacterial and plant marker genes, we have devised a versatile system for identifying plants in which a transposon has excised and reinserted elsewhere in the genome. The transposons have been designed to facilitate the identification of insertions downstream of promoters and in the vicinity of enhancers by the inclusion of a beta-glucuronidase (GUS) gene either lacking a promoter or having a minimal promoter sequence. The system permits the transposon and the source of transposase to be maintained either stably in separate plants or in the same plant. Plants in which transposition is occurring can be identified by the frequent somatic activation of the GUS gene. The herbicide chlorsulfuron is used as a selective agent to identify progeny plants in which the transposon has excised from its original insertion site within a chlorsulfuron-resistant acetolactate synthase gene. Additional selectable markers permit the identification of plants containing a transposed element, but lacking transposase. Here we describe our initial characterization of the system and demonstrate its reliability and efficiency in identifying plants with transposed elements.

Acetolactate Synthase↗

Epidemic of Pseudomonas cepacia in an adult cystic fibrosis unit: evidence of person-to-person transmission.

An epidemic of Pseudomonas cepacia occurred in an adult cystic fibrosis center in the United Kingdom, despite a policy of segregation of infected and noninfected patients within the hospital. Investigation of the outbreak by ribotyping and pulsed-field gel electrophoresis to characterize P. cepacia strain genomes together with inquiry into social contacts between patients revealed evidence of person-to-person transmission outside the hospital environment. Segregation policies aimed at reducing the spread of this infection in the cystic fibrosis community need to encompass patient contacts outside the hospital environment.

Adolescent↗

Molecular aspects of Mg2+ transport systems.

The gram-negative bacterium Salmonella typhimurium possesses three distinct Mg2+ transport systems, encoded by the CorA, MgtA, and MgtB loci. The CorA transport system is the constitutive Mg2+ influx system but can also mediate efflux at high extracellular Mg2+ concentrations. The CorA protein lacks homology to any known protein, is an integral membrane protein containing 28% percent-charged amino acids, and has three carboxyl terminal membrane-spanning segments. Its properties indicate that it is a new class of membrane transport protein, likely found in all gram-negative bacteria and possibly other organisms. In contrast, the MgtA and MgtB Mg2+ transport systems are normally expressed only at low extracellular Mg2+ concentrations and can mediate only the influx of Mg2+. Both MgtA and MgtB system are P-type ATPases; they have relatively poor homology to other known prokaryotic P-type ATPases but are highly homologous to mammalian P-type ATPases, particularly reticular Ca(2+)-ATPases. Expression of both MgtA and MgtB is highly regulated by the concentration of extracellular Mg2+. Transcription of MgtB is increased about 1,000-fold by lowering Mg2+ from 1 mM to 1 microM, and, under growth conditions of limiting Mg2+, MgtB becomes the dominant Mg2+ influx system. However, it is unclear why the cells require the use of ATP to mediate the influx of Mg2+ down its electrochemical gradient. Study of these Mg2+ transport systems should lead to further understanding of cellular Mg2+ homeostasis and eventually to characterization of eukaryotic Mg2+ transport systems.

Animals↗

Rates of carbamylation of specific lysyl residues in bovine alpha-crystallins.

Previous investigations indicate that some forms of cataract may be due to the reactions of isocyanate with lens proteins. The present investigation was directed toward identifying the products of these reactions and determining rate constants for their formation. Bovine alpha-crystallins were incubated with isocyanate and separated into alpha A- and alpha B-crystallins by reversed-phase HPLC (high-performance liquid chromatography). Products of the reaction of isocyanate with alpha-crystallins were analyzed by mass spectrometry and isoelectric focusing. Proteolytic digests of carbamylated alpha A were analyzed by HPLC and fast atom bombardment mass spectrometry to determine the extent of reaction of each of the 7 lysyl residues present in alpha A. These results demonstrate that incubation of alpha-crystallins in 0.1 M KNCO leads to partial carbamylation of all 7 lysines of alpha A-crystallin. The extent of modification after 24 h of incubation varied from 7% at Lys 88 to 61% at Lys 11. Rate constants for the reaction of specific lysyl residues with isocyanate ranged from 5 to 54 x 10(-2) M-1 h-1. The distribution of reaction products, as determined by isoelectric focusing, indicates that the physiologically relevant initial stages of carbamylation of the 7 lysyl residues of alpha A proceed in a noncooperative manner.

Amino Acid Sequence↗