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D Martin

Publications and source records attributed to D Martin.

At least 541 records · Page 30Linked to original sources
PubMed1992

Localization of conserved B-cell epitopes among encapsulated and non-encapsulated Haemophilus influenzae P2 porin proteins using synthetic peptides.

The P2 outer membrane protein of Haemophilus influenzae belongs to a class of apparently ubiquitous proteins in Gram-negative bacteria that function as porins. Murine hybridomas raised to the P2 protein and synthetic peptides were used to investigate the structural and antigenic relationships among P2 proteins of encapsulated and non-encapsulated H. influenzae. Three monoclonal antibodies (mAbs), P2-17, P2-18 and P2-19, recognizing epitopes on the P2 protein, as shown by Western immunoblotting of outer membrane preparations, and purified and recombinant P2 proteins are described. The epitopes reactive with the mAbs were widely distributed among H. influenzae strains since 70-100% of strains of encapsulated and non-encapsulated isolates collected worldwide were recognized by individual mAbs. None of the mAbs reacted with H. parainfluenzae or other bacterial species. The peptide composition of P2 epitopes was determined by analysis of mAb reactivity with a series of overlapping synthetic peptides that covered the amino acid sequences of H. influenzae type b. The domains recognized by these mAbs were completely distinct. mAb P2-18, reactive with an epitope conserved among all H. influenzae P2 porin molecules which were screened, recognized a peptide corresponding to the N-terminal segment (residues 1-14). The P2-17- and P2-19-specific epitopes were located between residues 28 and 55, and 101 and 129, respectively. None of the epitopes were exposed on the cell surface since no mAbs bound to intact live bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Haemodynamic effects of the calcium facilitator Bay K-8644 in rats following vascular calcium overload.

1. The haemodynamic effects of the Ca2+ facilitator Bay K-8644 (Bay) were studied in a model of calcinosis induced by acute treatment with vitamin D3 and nicotine administration over 4 days with 13 days of recovery. 2. Calcium content of the left ventricular myocardium increased 8-9 fold, while aortic Ca2+ levels increased up to 12-fold in treated animals. There were minimal changes in the ECG and no change in the level of plasma alpha-hydroxy-butyrate-dehydrogenase, a cardiac specific enzyme which increases during ischaemia. Significant increases in pulse pressure (PP) were seen in anaesthetized and conscious calcinotic rats, with no increase in cardiac output index (DABF) or systemic vascular resistance. However, aortic rigidity (AORI) was significantly elevated in the calcinotic group under anaesthesia. 3. In both control and calcinotic rats, pressor responses to i.v. Bay were exclusively mediated by an increase in aortic blood flow (DABF) as lower body vascular resistance (TLBVR) did not change. The increase in DABF at low doses (0.1-1 microgram kg-1) of Bay probably resulted from an increase in venous return induced by the agonist, as Bay had little effect on cardiac contractility over this dose range (as estimated by left ventricular dp/dtmax) and did not cause tachycardia. At higher doses (10-1000 micrograms kg-1), Bay significantly increased LV dp/dt. Bay caused dose-related increases in AORI in pithed calcinotic rats, but a decrease in AORI in control animals. 4. The calcinosis model, which incorporates a recovery period to obviate the acute effects of nicotine and/or vitamin D3 treatment, results in long-term tissue calcium accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Effects of prenatal ethanol exposure on hippocampal ionotropic-quisqualate and kainate receptors.

Previous studies from our laboratories have shown that the consumption of moderate quantities of ethanol by rat dams during pregnancy reduces N-methyl-D-aspartate (NMDA) agonist receptor binding and NMDA-mediated electrophysiological responses in the hippocampal formation of adult offspring. We hypothesized that prenatal ethanol exposure would produce similar effects on receptor number and agonist-mediated responses of two so-called "non-NMDA" subtypes of glutamate receptors, the ionotropic-quisqualate (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-sensitive and the kainate-sensitive receptors. Sprague-Dawley rats were fed either a liquid diet containing 3.35% ethanol, an isocalorically matched liquid diet, or lab chow ad libitum throughout gestation. No significant differences between offspring from these three groups in the agonist concentration-response curves for either AMPA-induced or kainate-induced depolarization of hippocampal CA1 pyramidal neurons were observed. Furthermore, no significant differences in the density of [3H]-AMPA or [3H]-vinylidene kainic acid binding sites in any of the apical dendritic field regions of dorsal or ventral hippocampal formation were observed between the groups. These results indicate that the ionotropic quisqualate and kainate receptors, located in the apical dendritic field regions of the principal hippocampal neurons, are not affected by the same degree of prenatal ethanol exposure, which is known to reduce NMDA receptor binding and function in these same regions.

Animals↗
PubMed1992

Use of event markers during exercise testing to optimize morphology criterion programming of implantable defibrillator.

The present generation implantable defibrillator introduced on-line event markers that can be used to evaluate tachycardia detection in the electrophysiological testing mode. These markers were used to assess the appropriateness of programming the morphology criterion for detection of ventricular tachycardia. Twenty-one consecutive patients (19 men, 2 women) performed 29 bicycle exercise tests with real-time recording of the electrocardiogram and the event markers on a multichannel recorder. Mean ejection fraction was 29% (range 15%-69%). Seven patients were taking antiarrhythmic agents. Twelve patients satisfied the morphology criterion at rest (n = 1) or during exercise (group I), and nine patients did not (group II). One patient was excluded from analysis because of continuous ventricular pacing. Mean peak heart rate was 130 beats/min in group I and 125 beats/min in group II. No statistical differences existed between the groups in relation to cycle length of ventricular tachycardia and mode of induction of arrhythmia, QRS duration on the electrocardiogram, during native rhythm, amplitude and duration of defibrillation patch R wave, calculated duty cycle at peak heart rate, and number of discharges of the automatic implantable cardioverter defibrillator at 2 to 14 months of follow-up time. It is concluded that clinical, electrocardiographic, and implantation data are unreliable in predicting satisfaction of the morphology criterion during high heart rates in native rhythm. Formal exercise testing in the electrophysiological mode enables a rational decision to be made about the appropriateness of the use of probability density function in each patient.

Algorithms↗
PubMed1992

Immunological characterization of the lipooligosaccharide B band of Bordetella pertussis.

Two structurally and immunologically different components of Bordetella pertussis endotoxin can be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining: a major A band and a faster-migrating minor B band. Certain mutant strains of B. pertussis express only the B band, while the wild-type strains produce both lipooligosaccharides (LOS). Two monoclonal antibodies (MAbs) directed against the minor LOS B band were generated, allowing the study of this surface molecule on different strains of Bordetella. These two MAbs, designated BL-8 and BL-9, reacted strongly with phenol-water-purified LOS obtained from a B. pertussis LOS B mutant strain. Sodium periodate treatment of the purified LOS prevented binding of the MAbs, indicating the carbohydrate nature of the epitope(s). Western immunoblotting experiments revealed that the epitope(s) recognized by these MAbs is conserved on all B. pertussis and Bordetella bronchiseptica Vir- (avirulent) variant strains tested but is not present on Bordetella parapertussis and B. bronchiseptica Vir+ (virulent) wild-type strains. Further studies showed that although present in the lipopolysaccharide B band expressed by Vir- strains, the epitope(s) recognized by the MAbs is not accessible on the surface of intact B. bronchiseptica cells. For B. pertussis, the density and accessibility of this epitope(s) are dependent on the virulence-associated or LOS phenotype expressed by the strain. Our data demonstrate that the expression and accessibility of the epitope(s) are significantly greater on the LOS B variant strains and LOS AB Vir- strains compared with fresh B. pertussis clinical isolates. For these latter strains, which are Vir+, this epitope(s) was barely detectable on the surface of intact bacteria, despite Western blot analyses that revealed specific reactions between the MAbs and the LOS B band. The two LOS B-specific MAbs had no bacteriolytic activity against a LOS AB wild-type strain, while the control MAb BL-2, which is specific for the B. pertussis LOS A band, significantly reduced the number of living bacteria in the same assay. Moderate lytic activity against a mutant strain expressing only the LOS B band was observed for MAb BL-8 but not for MAb BL-9 or BL-2. These data demonstrate that the type, amount, and surface exposure of the LOS are related to the phenotype expressed by a specific B. pertussis strain. In addition, the LOS B MAbs also reveal the antigenic conservation of carbohydrate epitopes among B. pertussis and B. bronchiseptica strains.

Animals↗
PubMed1992

Validity of pulse oximetry during exercise in elite endurance athletes.

Eleven highly trained male cyclists [maximal aerobic power (VO2max) = 70.6 +/- 4.2 ml.kg-1.min-1] performed both high intensity constant load (90-95% VO2max) and incremental cycle exercise tests with arterial blood sampling to evaluate the accuracy of pulse oximeter estimates (%SpO2) of arterial oxyhemoglobin fraction of total hemoglobin (%HbO2). Three subjects also performed an incremental exercise test in hypoxic conditions (inspired partial pressure of O2 = 89, 93, or 100 Torr). Arterial %HbO2 was determined via CO-oximetry and ranged from 72 to 99%. Three Ohmeda 3740 pulse oximeters were used to estimate %HbO2, one on each ear lobe and a finger probe. The finger probe tended to provide the best estimate of %HbO2 during exercise: the mean %SpO2 - %HbO2 difference for 232 exercise observations was 0.52 +/- 1.36% (SD). Finger probe %SpO2 and %HbO2 were highly correlated [r = 0.98, standard error of the estimate (SEE) = 1.32%, P less than 0.0001]. The accuracy of pulse oximeters has been questioned during high-intensity exercise. When aerobic power was greater than 81% of VO2max (n = 75), the finger probe's mean error was -0.01 +/- 1.40%. Finger probe %SpO2 and %HbO2 were highly correlated (r = 0.97, SEE = 1.32%, P less than 0.0001). These results indicate that this pulse oximeter is a valid predictor of %HbO2 in elite athletes during cycle exercise.

Adult↗
PubMed1992

Aging and respiratory muscle metabolic plasticity: effects of endurance training.

We examined the oxidative and antioxidant enzyme activities in respiratory and locomotor muscles in response to endurance training in young and aging rats. Young adult (4-mo-old) and old (24-mo-old) female Fischer 344 rats were divided into four groups: 1) young trained (n = 12), 2) young untrained (n = 12), 3) old trained (n = 10), and 4) old untrained (n = 6). Both young and old endurance-trained animals performed the same training protocol during 10 wk of continuous treadmill exercise (60 min/day, 5 days/wk). Compared with young untrained animals, the young trained group had significantly elevated (P less than 0.05) activities of 3-hydroxyacyl-CoA dehydrogenase (HADH), glutathione peroxidase (GPX), and citrate synthase (CS) in both the costal diaphragm and the plantaris muscle. In contrast, training had no influence (P greater than 0.05) on the activity of lactate dehydrogenase within the costal diaphragm in young animals. In the aging animals, training did not alter (P greater than 0.05) activities of CS, HADH, GPX, or lactate dehydrogenase in the costal diaphragm but significantly (P less than 0.05) increased CS, HADH, and GPX activities in the plantaris muscle. Furthermore, training resulted in higher activities of CS and HADH in the intercostal muscles in the old trained than in the old untrained animals. Finally, activities of CS, HADH, and GPX were significantly (P less than 0.05) lower in the plantaris in the old untrained than in the young untrained animals; however, CS, HADH, and GPX activities were greater (P less than 0.05) in the costal diaphragm in the old sedentary than in the young untrained animals.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1992

Biochemical modulation of bolus fluorouracil by PALA in patients with advanced colorectal cancer.

PURPOSE: N-(phosphonacetyl)-L-aspartic acid (PALA) is a pyrimidine synthesis inhibitor that modulates fluorouracil (FU) cytotoxicity. Two previous studies of patients with colorectal carcinoma documented complete response (CR) and partial response (PR) rates of 40% and 43% using weekly low-dose PALA followed by a 24-hour FU infusion. We investigated whether comparable results could be obtained with biochemical modulation by low-dose PALA using bolus instead of infusional FU. PATIENTS AND METHODS: Forty-five patients without prior chemotherapy who had advanced colorectal carcinoma were treated with PALA 250 mg/m2 followed 24 hours later by bolus FU at three dose levels, 600, 700, 800 mg/m2, repeated weekly for 6 weeks followed by a 2-week break. RESULTS: The CR and PR rate was 15 of 43 patients or 35% (95% confidence interval [CI], 21% to 49%), with an overall median survival of 18 months. Grade 3 or 4 diarrhea was the major toxicity observed in 24% of patients receiving FU at 700 mg/m2 and in 43% of patients receiving 800 mg/m2. Hematologic toxicity was observed only with an FU dose of 800 mg/m2, and 29% (four of 14) of patients developed grade 4 leukopenia. We also noted the development of ascites in six patients, mild hyperbilirubinemia in 16 patients, and a decreased albumin level in 22 patients; these abnormalities occurred more frequently in responding patients. CONCLUSIONS: The observed response rate, median survival, and toxicity in this study are similar to those obtained with PALA plus infusional FU and with other methods of FU modulation. Larger phase III studies are needed to compare bolus FU/PALA regimens with other PALA and non-PALA-containing combinations. Our future focus will be attenuate this regimen's toxicity while maintaining or improving its response rates and survival.

Adenocarcinoma↗
PubMed1992

Postcodes and the 1991 census of population: issues, problems and prospects.

"The decade between the 1981 and 1991 UK Censuses of Population has seen an enormous increase in the use of the postcode system for locational referencing. To date, no direct means have existed for linking postcoded data to census geography at the most detailed level, but the production of a new ED/postcode directory promises to offer a range of new opportunities for postcode applications following the release of the 1991 Census data. This paper reviews the characteristics of the postcode system, describes the new directory, and examines the methods which will be available for linking the Census and postcodes post-1991."

Censuses↗
PubMed1992

[Role of osteocutaneous external brachial flap in the treatment of composite loss of substance of the mandible].

The authors report on their research begun in 1987 on this flap and its uses in reconstruction of composite defects of the horizontal and symphysical parts of the mandible, regardless of the cause of the loss. For treatment of average sized defects (less than 7 centimeters), it is reliable flap, easy to remove and to model by osteotomies, giving a thin skin mobile with bone and the removal of which results in only moderate development of scar tissue at the donor site.

Arm↗
PubMed1992

Kindling enhances sensitivity of CA3 hippocampal pyramidal cells to NMDA.

Kindling is a form of experimental epileptogenesis in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. Previous studies suggested that kindling might be explained, at least in part, by an increased sensitivity of brain neurons to NMDA receptor agonists. This possibility was investigated with the use of grease-gap preparations for assaying the depolarizing responses of CA3 and CA1 hippocampal pyramidal cells to amino acid excitants. When studied 1-2 months after the last evoked seizure, CA3 pyramidal cells from kindled rats were five- to sixfold more sensitive to NMDA than CA3 pyramidal cells from controls. A similar, though smaller, effect of stimulation was observed 1 d after the last evoked seizure. The greater potency of NMDA in kindled rats can probably be explained by enhanced expression of NMDA receptors in the presence of a receptor reserve. The stimulation protocol did not alter the ability of Mg2+ to reduce NMDA potency. It also affected neither the response of CA3 pyramidal cells to AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate] nor the response of CA1 pyramidal cells to NMDA or AMPA. In area CA3, the potency of NMDA, but not of AMPA, declined 2.5-4-fold over the 1-2 month experimental period, apparently as a result of increasing age. This age-related loss of sensitivity to NMDA was completely prevented by kindling. These findings suggest that kindling prevents a loss of NMDA receptor function in CA3 pyramidal cells that normally occurs during early adulthood. Such a change could contribute to maintenance of the kindled state.

Aging↗
PubMed1992

Simultaneous patient-side measurement of hemoglobin, glucose, and cholesterol in finger-stick blood.

We describe a multianalyte assay system for patient-side use comprising single-use plastic cartridges and a small monitor. Hemoglobin, glucose, and cholesterol can be simultaneously measured in 3 min in an unmeasured volume of blood. The sample is drawn by capillary action into four channels for delivery to assay-specific stacks containing a set of closely apposed layers. The distal layer is a membrane that acts as the optical surface for reflectance optics. For glucose and cholesterol assays, erythrocytes are removed by a fibrous filter layer and oxidase-peroxidase chemical reactions contained in the optical membrane generate a colored product. For hemoglobin measurement, blood is lysed by detergent contained in a porous disk. The amount of color reaching the optical membrane is measured by fiber optics. To ensure fail-safe operation, sensors verify sample sufficiency and degree of hemolysis. The assays perform comparably with laboratory methods.

Blood Glucose↗
PubMed1992

MRI assessment of anterior callosotomy in the treatment of pharmacoresistant epilepsy.

Section of the anterior two-thirds of the corpus callosum is a well-known treatment of some forms of epilepsy of long duration resistant to anti-epileptic drugs and dangerous for the patient (tonic and atonic seizures). The aim of this functional surgery is to obtain the most complete rostral and caudal section of the corpus callosum without risk of disconnection syndrome. Callosotomy is seldom performed in Europe. We present our experience of magnetic resonance imaging (MRI) in the pre- and postoperative assessment of 6 patients who underwent anterior callosotomy and were followed up for more than six months. Our results were encouraging with considerable improvement of the patients' social life.

Adolescent↗
PubMed1991

A new syndrome: ascites, hyperbilirubinemia, and hypoalbuminemia after biochemical modulation of fluorouracil with N-phosphonacetyl-L-aspartate (PALA)

OBJECTIVE: To report a new syndrome of ascites, hyperbilirubinemia, and hypoalbuminemia after treatment with N-phosphonacetyl-L-aspartate (PALA) and fluorouracil for metastatic colorectal cancer. DESIGN: Retrospective analysis. SETTING: Regional cancer treatment center. PATIENTS: Forty-four previously untreated patients with metastatic colorectal cancer in a phase I-II trial of PALA-fluorouracil. MEASUREMENTS AND MAIN RESULTS: One or more transient hepatic abnormalities frequently occurred in 15 of the 17 responding patients. Within the first 10 weeks of treatment, 5 patients developed ascites, 12 had a decrease in the serum albumin level, 6 developed bilirubin elevations, and 7 had transaminase elevations, all in the presence of a complete or partial tumor response. Prolongations of the prothrombin time and elevations of serum glucose levels were also seen. CONCLUSIONS: An unusual syndrome of ascites, hyperbilirubinemia, and hypoalbuminemia is associated with a PALA-fluorouracil regimen. These abnormalities, which may be related to decreased hepatic protein synthesis, occurred more often in patients whose tumor was responding to chemotherapy. Clinicians must recognize that in patients undergoing chemotherapy with these agents, ascites and elevated liver function tests may be secondary to drug administration and are not necessarily due to disease progression.

Aged↗
PubMed1991

Ethanol inhibition of NMDA mediated depolarizations is increased in the presence of Mg2+.

The inhibitory potency of ethanol upon excitatory amino acid induced depolarizations of rat hippocampal CA1 pyramidal cells was assessed in the presence and absence of magnesium (Mg2+) using the grease-gap technique. Ethanol shifted the N-methyl-D-aspartate (NMDA) dose-response curves to the right in a non-parallel manner. In the presence of Mg2+, ethanol appeared to be a more effective NMDA antagonist (IC50 47 mM) than in the absence of Mg2+ (IC50 107 mM). The IC50 for ethanol upon non-NMDA mediated CA1 pyramidal cell depolarizations was in excess of 170 mM. These results strongly suggest a preferential inhibitory action of ethanol against NMDA, rather than non-NMDA, mediated responses. Experiments in which ethanol and Mg2+ were covaried indicated that these substances act by two distinct mechanisms to antagonize the action of NMDA. These effects of ethanol, at concentrations which elicit intoxication (less than 50 mM) but not anesthesia, suggest that the NMDA receptor complex may play an important role in the acute effects of ethanol.

Animals↗
PubMed1991

Grafts of syngenic cultured, adult dorsal root ganglion-derived Schwann cells to the injured spinal cord of adult rats: preliminary morphological studies.

Highly enriched cultures of Schwann cells were obtained from adult rat dorsal root ganglia and implanted (5 x 10(5) -9 x 10(5) cells) in the spinal cord of syngenic adult rats at the site of an acute compression lesion produced by a subdural inflatable microballoon. These autografts survived and invaded the host tissue, reducing central cavitation and astrocytic gliosis. They dramatically promoted ingrowth of axons, the majority of which appeared to come from the dorsal roots as judged by their neuropeptide content. Invasion of the transplants by descending, e.g. aminergic fibers, was negligible at survival times of up to 4 months. Nonetheless, autologous Schwann cells, which are readily available in the host, represent a promising material for grafts into the injured spinal cord.

Animals↗