Biomedical subjects

C M Lucas

Publications and source records attributed to C M Lucas.

At least 19 recordsLinked to original sources

PubMed1994

Efficacy of 28-day and 40-day regimens of sodium stibogluconate (Pentostam) in the treatment of mucosal leishmaniasis.

The efficacy and toxicity of two regimens of antimony, 28 and 40 days of 20 mg of antimony/kg/day, were compared in the treatment of culture-positive mucosal leishmaniasis involving more than one anatomic site. Forty consecutive eligible Peruvians with infiltrative or ulcerative mucosal disease of the lips, nose, palate-uvula-pharynx, or larynx-epiglottis were randomized to receive either 28 days (P28) or 40 days (P40) of sodium stibogluconate (Pentostam). Treatment was prematurely terminated due to thrombocytopenia in three patients and two patients did not complete six months of follow-up. At one month post-treatment, 13% (2 of 16) of the P28 patients and 16% (3 of 19) of the P40 patients no longer had infiltrates or ulcers and were initially considered cured. During a further 11 months of follow-up, infiltrated lesions healed in eight more P28 patients and in 10 more P40 patients. The cure rate after 12 months of follow-up was therefore 63% for both groups (10 of 16 in the P28 group and 12 of 19 in the P40 group). The total of 13 patients who had infiltrates or ulcers at the 9-12-month follow-up were considered failures. All seven patients (three in the P28 group and four in the P40 group) whose lesions were culture-positive for Leishmania at some point in the 12 months after treatment, and who were thereby parasitologic failures, were also clinical failures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Leishmania (Viannia) lainsoni: first isolation in Peru.

Surveys were conducted from 1986 through 1992 to define the etiology and geographic distribution of human leishmaniasis in Peru. Lesion aspirates and skin biopsies were obtained from clinically diagnosed cases of leishmaniasis and tested for promastigotes by standard culture techniques. The isozyme profile of the isolates was determined by the cellulose acetate electrophoresis technique. Data indicated that the isozyme profiles for Leishmania isolates from six patients were similar to that of reference strains of L. lainsoni. These results are the first reported evidence of L. lainsoni and the first association of this parasite with human cases of cutaneous leishmaniasis in Peru.

Adolescent↗

PubMed1993

A new stimulation protocol for cardiac assist using the latissimus dorsi muscle.

When treating severe cardiac failure with dynamic cardiomyoplasty, knowledge about the optimal way of stimulating the latissimus dorsi (LD) muscle is of obvious importance. We evaluated a new stimulation protocol in four goats using in situ electrical stimulation of the left LD muscle. Stimulation was started using a burst of two pulses with an interpulse interval of 100 msec for 50 bursts/min. The number of pulses was increased every 2 weeks concomitant with a decrease in interpulse interval. This resulted after 12 weeks in 60 bursts/min using bursts of six pulses with an interpulse interval of 20 msec after 12 weeks. Force measurements, which were done every 2 weeks, showed an early decrease in contraction and relaxation speed as reflected in the ripple (= interstimulus amplitude/peak force amplitude measured at 10 Hz). Fatigue resistance increased significantly within 4 weeks of conditioning as indicated by preservation of force, positive dF/dt, and negative dF/dt. Full preservation of these variables was seen even during a 1-hour fatigue test at the end of the conditioning period. Skeletal muscle enzyme activity as an indicator of muscle damage showed a significant rise in creatine kinase enzyme activity only on the first day following the start of LD stimulation. LD muscle biopsies revealed almost complete transformation to type I muscle fibers with a significant increase in capillary/fiber ratio when compared to the nonstimulated LD muscle. However, some biopsies, in particular near the electrodes, did show some signs of skeletal muscle damage. Contraction characteristics of the fully transformed LD muscles were tested by increasing the number of bursts of six pulses from 50/min to 100/min. Interpulse intervals of 20 and 33 msec were used. These tests revealed that maximal force, positive dF/dt, and negative dF/dt was reached with 50 bursts/min using a six pulse burst with interpulse intervals of 20 msec.

Animals↗

PubMed1992

Adaptation of energy metabolism of canine latissimus dorsi muscle in response to chronic electrical stimulation.

Transformation of the latissimus dorsi (LD) muscle from a fast-twitch, fatigue-prone to a fatigue-resistant ("heart-like") muscle, necessary to allow its application in cardiac assist devices, can be induced by chronic electrical stimulation. In adult dogs we studied the nature and time course of myofibrillar and metabolic adaptations in the LD muscle when exposed in situ to 24 weeks of continuous electrical stimulation. In addition, the metabolic properties of the stimulated muscle were compared with those of canine cardiac muscle. The proportion of immunohistochemically identified type I fibres increased on stimulation from 28% to 80%, while that of type II fibres decreased from 69% to 16%. Fibres of intermediate type (IIC and IC) appeared transiently; the highest levels were found between 4 and 8 weeks of stimulation. The activities of fructose-6-phosphate kinase and lactate dehydrogenase (LDH), which before stimulation were similar to those in heart, decreased to 18% and 34% of their initial values respectively. However, the LDH isozyme pattern changed towards that typical for cardiac muscle. These changes indicate a markedly decreased flux capacity through the glycolytic pathway which, however, is directed more towards the oxidative conversion of substrates. The mitochondrial capacity (maximal palmitate oxidation and pyruvate dehydrogenase complex activities) of the muscle did not change and remained at a level less than half of that of cardiac ventricular muscle. Contents of adenine nucleotides and endogenous substrates were maintained during stimulation. No further changes in the observed adaptations occurred after week 12 of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1992

Imipramine induced heart failure in the dog: a model to study the effect of cardiac assist devices.

OBJECTIVE: The value of intravenous imipramine in creating a reversible model of short term heart failure was evaluated in anaesthetised dogs. METHODS: Acute effects of imipramine were studied in 11 dogs using invasive haemodynamic pressure measurements and two dimensional echo evaluation. RESULTS: After a 30 min imipramine infusion (7.5 mg.kg-1.h-1), positive left ventricular dP/dtmax decreased from 1368(SEM 108) to 909(119) mm Hg.s-1 (p < 0.05), left ventricular end diastolic pressure increased from 8(1) to 12(2) mm Hg (p < 0.05), while left ventricular pressure decreased from 106(4) to 87(6) mm Hg (p < 0.05). Cessation of imipramine administration resulted within 60 min in partial restoration of cardiac function. This deterioration and subsequent recovery was also demonstrated with echocardiographic measurements, which showed a decrease in ejection fraction from 54(3)% to 28(2)% (p < 0.05). During administration of imipramine neither significant electrophysiological changes nor supraventricular/ventricular arrhythmias were seen. Repeated infusions of imipramine in three anaesthetised dogs with a two week interval showed the reproducibility of the haemodynamic effects and the recovery of ventricular function. Since the model was developed to evaluate the use of cardiomyoplasty in heart failure, the effect of imipramine was also evaluated on latissimus dorsi muscle contraction. Administration of imipramine did not affect skeletal muscle force development at the dosage used to create heart failure. CONCLUSIONS: This model can be used to produce short term reversible heart failure in anaesthetised animals to test the efficacy of supportive interventions like dynamic cardiomyoplasty, intra-aortic balloon pumping, and mechanical cardiac assist devices.

Animals↗

PubMed1992

The importance of muscle relaxation in dynamic cardiomyoplasty.

During the last decade dynamic cardiomyoplasty has been introduced as a new method to treat patients with severe heart failure. This procedure consists of the wrapping of the latissimus dorsi (LD) muscle around the heart with electrical stimulation of the muscle synchronous to cardiac contraction. The optimal pacing mode of the muscle, during the conditioning and working period of the LD muscle, is still unclear. The pace protocol, currently used worldwide, has a maximal number of muscle tetanic contractions of 100 per minute. Data are presented on the LD muscle contraction characteristics using that protocol. Both force measurements from six in situ stimulated goat LD muscles and x-ray evaluation of the movement of metallic clips on wrapped LD muscles in two patients were used. Results demonstrate that LD muscle force is well maintained at the maximal rate of 100 contractions per minute but relaxation is severely hampered. This may lead to diminished support of the failing heart and damage of the wrapped muscle. A pacing protocol is proposed using a lower maximal stimulation rate.

Animals↗

PubMed1992

Changes in canine latissimus dorsi muscle during 24 wk of continuous electrical stimulation.

To study functional, structural, and biochemical adaptations to electrical stimulation of striated muscle in a large animal, the canine latissimus dorsi (LD) muscle was conditioned continuously for 24 wk with an increasing number of pulse bursts (burst duration 250 ms, burst frequency 30 Hz). Force measurements in vivo after 12 wk showed a significant decrease in the ripple, the ratio of interstimulus to peak force amplitude, from 0.94 +/- 0.03 to 0.13 +/- 0.08 (SE; n = 8, P less than 0.05), indicating reduction in contractile speed. Also the steep part of the force-frequency relation shifted to lower frequencies. A significant change in fiber-type composition was seen with both enzyme- and immunohistochemistry, manifested by an increase of type I fibers from 29.5 +/- 2.9 to 83 +/- 8% (SE; n = 8, P less than 0.05). During this period a transient rise in the number of type IIc/Ic fibers (from 3 to 10%) was seen. In the stimulated muscle, capillary-to-fiber ratio increased from 1.9 +/- 0.4 to 2.7 +/- 0.1 (P less than 0.05). A significant increase in mitochondrial volume was also seen, especially in the peripheral part of the fiber. Both creatine kinase and lactate dehydrogenase revealed a significant decline in activity within 12 wk. At the same time a shift in lactate dehydrogenase-isozyme pattern was observed toward the cardiac composition. No additional changes occurred after 12 wk of stimulation, indicating that conversion of the canine LD muscle was complete within this period.

Adaptation, Physiological↗

PubMed1992

Differences in metabolic response of dog and goat latissimus dorsi muscle to chronic stimulation.

The latissimus dorsi (LD) muscle is considered suitable to assist ventricular mechanical function in either cardiomyoplasty or extra-aortic-assist devices. Such application requires that this mixed-type skeletal muscle be transformed into a fatigue-resistant muscle, the adaptation of which can be elicited by chronic stimulation. In this study the LD muscles of dog and goat were subjected in situ to 12 wk of continuous electrical stimulation through intramuscular electrodes, and their myofibrillar and metabolic adaptations were compared. A gradual increase in the contraction rate of the muscle (in 10 wk from 30 to 80 contractions/min) caused the proportion of immunohistochemically identified type I fibers to increase in dog muscle from 30 to 74% and in goat muscle from 21 to 99%. Correspondingly, the anaerobic-glycolytic activity (fructose-6-phosphate kinase and lactate dehydrogenase activities) decreased by approximately 75% in both dog and goat muscles, whereas the oxidative capacity (fatty acid oxidation and citrate synthase activity) increased two- to threefold in goat LD muscle but remained unaltered in dog LD muscle. Muscular contents of high-energy phosphates and endogenous substrates were maintained, but the L-carnitine content decreased by 43% in both dog and goat. Our data further indicate that, for the monitoring of the metabolic adaptation of skeletal muscle, the ratio of activities of the oxidative and anaerobic-glycolytic pathways (e.g., citrate synthase to fructose-6-phosphate kinase activities) is a useful parameter in both dog and goat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1992

Antibody response to the circumsporozoite protein of Plasmodium vivax in naturally infected humans.

The circumsporozoite (CS) protein of Plasmodium vivax consists of a central repeat region flanked by highly conserved non-repeat regions. Serum samples from 33 individuals with naturally acquired infections of P. vivax were tested for antibodies to four antigens representing the vivax CS protein. Three recombinant proteins containing different overlapping sequences in the non-repeat regions and either the entire central repeat region (vivax-1 and vivax-2) or two of the repeat sequences (vivax-3) were used as antigens in an enzyme-linked immunosorbent assay (ELISA). Antibodies to two other proteins, one (NS1(81)V20) containing the entire predominant repeat region (GDRAA/DGQPA) and the other (Pvk247) containing the variant repeat sequence (ANGAGNQPG) that was recently reported from Thailand were also measured by ELISA. Immunoglobulin G antibodies to the antigen representing the predominant repeat were present in 15% of the patients on the first day of treatment (day 0) and in 24% of the patients two weeks later (post-treatment). Six and 12% of the patients had IgG antibodies to the antigen containing the variant repeat on day 0 and post-treatment, respectively. A larger proportion of the sera had antibodies to the three antigens containing the non-repeat sequences; on the first day of treatment and two weeks later, 79 and 97% of the patients, respectively, had antibodies to vivax-1, vivax-2, and vivax-3. In this sample of Peruvians naturally infected with P. vivax, the most prevalent antibody responses were targeted to epitopes in the non-repeat region of the CS protein rather than to epitopes in the repeat region.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Prevalence of antibody to the variant repeat of the circumsporozoite protein of Plasmodium vivax in Peru.

Individuals living in a malaria-endemic area in northern Peru were found to have antibodies to the variant repeat sequence of the circumsporozoite (CS) protein of Plasmodium vivax. The presence of IgG antibody to the predominant repeat sequence GDRAA/DGPA represented by the recombinant protein NS1(81) V20 (V20), and the variant repeat sequence ANGAGNQPG contained in the synthetic peptide Pvk247, was determined by enzyme-linked immunosorbent assay. IgG antibodies to the repeats were present in 78 (26%) of 298 serum samples; 56% of the positive serum samples had antibodies to V20 and 60% had antibodies to Pvk247. These findings stress the importance of considering the variant epitope in designing a vaccine based on the repeat region of the vivax CS protein. In a malaria-endemic area such as the one in this study, in which exposure to the variant repeat epitope may be as frequent as exposure to the predominant repeat, a vaccine based solely on the predominant repeat epitope may be ineffective against the variant form.

Adolescent↗

PubMed1991

Individual embryonic fibroblasts express multiple beta chains in association with the alpha v integrin subunit. Loss of beta 3 expression with cell confluence.

The alpha chain of the vitronectin receptor, alpha v, has been found in association with the integrin subunits beta 1, beta 3, or beta 5 on different cell types. We show here that cultured embryonic fibroblasts simultaneously display alpha v beta 3, alpha v beta 1, and alpha v in association with two other beta subunits, one of which is probably beta 5. Polymerase chain reaction analysis of single cells isolated by micromanipulation identified mRNA for alpha v, beta 1, beta 3, and beta 5 in six of eight clones. Immunoprecipitation of iodinated cell surface proteins with a monoclonal antibody to alpha v indicated that the relative proportions of the different beta chains in association with alpha v varied, particularly between two different cell lines. The cytokines platelet-derived growth factor, transforming growth factor beta 1, and tumor necrosis factor alpha did not appear to alter this ratio although tumor necrosis factor alpha increased the surface expression of the alpha v-associated integrins; but overnight culture in basic fibroblast growth factor caused a lower expression of alpha v beta 1 and alpha v beta 5 with no reduction in alpha v beta 3 expression. When the cell cultures were grown to complete confluence, surface expression of beta 3 was abolished, and the expression of an unknown beta chain (beta u) became more prominent. This effect was not overcome by culturing confluent cells with basic fibroblast growth factor. Affinity column chromatography showed that alpha v beta 5 bound to vitronectin but alpha v beta 1 did not, whereas alpha v beta 1 but not alpha v beta 5 bound to fibronectin. These results suggest that, on individual cells, the beta subunits found in association with alpha v may vary according to the proliferative capacity of the cell and that the promiscuous beta 3 subunit is progressively replaced by beta subunits of individual ligand specificity.

Base Sequence↗

PubMed1991

GMP-140 binding to neutrophils is inhibited by sulfated glycans.

GMP-140 is a 140-kDa granule membrane glycoprotein localized to the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells. Expression of GMP-140 on the activated cell surface has been shown to mediate the adhesion of thrombin-activated platelets to neutrophils and monocytes and the transient adhesion of neutrophils to endothelium. In contrast, fluid-phase GMP-140 strongly inhibits the CD18-dependent adhesion of tumor necrosis factor alpha-activated neutrophils to endothelium suggesting that GMP-140 can also serve an anti-adhesive function. In the present report, it is demonstrated that fluid-phase GMP-140 which exists predominantly as a tetramer binds to a single class of high affinity receptor on neutrophils and HL60 cells. Binding of 125I-labeled GMP-140 to neutrophils and HL60 cells and the rosetting of neutrophils and HL60 cells by thrombin-activated platelets were inhibited by EDTA, excess unlabeled fluid-phase GMP-140, Fab fragments of an affinity-purified rabbit anti-GMP-140 antibody, and by the murine anti-GMP-140 monoclonal antibody, AK 4. Both neutrophil and HL60 GMP-140 binding and platelet rosetting were strongly inhibited by heparin, fucoidin, and dextran sulfate 500,000, were partially inhibited by dextran sulfate 5,000 and lambda- and kappa-carrageenan, but were not inhibited by chondroitins 4- and 6-sulfate. Since this sulfated glycan specificity is identical to that previously reported by us for GMP-140, the present results suggest that the sulfated glycan binding site and the neutrophil receptor binding site on GMP-140 are either identical or proximal.

Antibodies, Monoclonal↗

PubMed1991

Adhesion protein GMP140 inhibits superoxide anion release by human neutrophils.

The respiratory burst of blood neutrophils has a critical role in the destruction of microorganisms and tissue damage in inflammation. Neutrophils adhere in a dose-dependent fashion to granule membrane protein 140 (GMP140), a member of the LEC-CAM (lectin/epidermal growth factor/complement-binding domain cell adhesion molecule) family of adhesion proteins when it is immobilized onto plastic surfaces. Adherence to GMP140 was associated with less superoxide anion generation than adherence to other surfaces, an effect that is especially remarkable after activation of neutrophils with tumor necrosis factor alpha, an agent that on other surfaces promotes adhesion and spreading. However, on GMP140 the cells fail to spread and instead remain rounded and refractile. Neutrophils adhering to GMP140 were also deficient in superoxide anion generation to formylmethionylleucylphenylalanine. Furthermore, fluid-phase GMP140 also inhibited the superoxide generation by neutrophils stimulated by tumor necrosis factor alpha. The effect of GMP140 was reversible by washing and was inhibited by anti-GMP140 Fab antibody. GMP140 appears to be a natural antiinflammatory molecule that may prevent the inappropriate activation of neutrophils in the circulation.

Antibodies↗

PubMed1991

What is the ideal pulse frequency for skeletal muscle stimulation after cardiomyoplasty?

Routinely the latissimus dorsi (LD) muscle is stimulated with bursts of pulses at 30 pulses/sec after cardiomyoplasty to assist the failing heart. At a lower pulse frequency the contractile force decreases and at higher frequencies the energy demand of the pacemaker increases rapidly. We investigated the effect of the stimulus frequency variation on contractile force in untrained LD muscles and in muscles after 12 weeks of continuous cyclic electrical stimulation. In six dogs, two electrodes (Medtronic SP5528) were implanted in the left LD muscle together with an Itrel muscle stimulator. The LD muscle was stimulated with 30 pulses/sec in bursts to deliver initially 30 and after 10 weeks 80 contractions per minute. Both before and after training of the LD muscle maximum force was observed by stimulating with a frequency of 36 to 130 pulses/sec in a burst. However, training induced a shift in the steep part of the force-frequency relation to lower frequencies. In particular, at 15 pulses/sec 60% of the maximal force was obtained in contrast to 40% before training. A fatigue test of 8 minutes duration was performed specified by 100 bursts/min and a burst duration of 0.25 sec at pulse frequencies of 30, 36, 50, and 85 pulses/sec. The contractile force decreased significantly during the course of the test at all frequencies. However, the force obtained with 30 pulses/sec stimulation was lower during the initial phase and approximately 10% higher at the end of the fatigue test as compared to 36, 50, and 85 pulses/sec stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Canine-specific adaptation of energy metabolism of latissimus dorsi muscle in response to chronic electrical stimulation.

Continuous electrical stimulation ot canine latissimus dorsi (LD) muscle in situ during 24 weeks induced an increase of immunohistochemically assayed type I fibers from about 30 to 80%. Concomitantly, the activity of fructose-6-phosphate kinase, a key enzyme of the glycolytic pathway, declined markedly, but the capacity for fatty acid oxidation remained unaltered. With respect to myofibrillar and metabolic properties the dog LD muscle initially resembled soleus muscle, and after 24 weeks of stimulation had acquired the properties of gastrocnemius muscle. It is concluded that in the dog, unlike the rat, the LD muscle has an inherently fixed capacity for oxidative energy production. Further expansion of its resistance to fatigue, as induced by chronic stimulation, most likely results mainly from a more efficient coupling between tension development and energy production.

Adaptation, Physiological↗

PubMed1991

The effect of L-carnitine on force development of the latissimus dorsi muscle in dogs.

Using the latissimus dorsi (LD) muscle of the dog in situ, the effect of carnitine was tested for increase of force in the first period after stimulation. Carnitine administration resulted in an increase of force of 31 +/- 6% (mean +/- SEM). It is hypothesized that, during muscle stimulation, a relative carnitine deficiency occurs in cells of the vascular compartment. The previously observed lesser effect of carnitine in the trained muscle than in the untrained muscle is in line with this hypothesis, since the number of capillaries is known to increase by training. Also in agreement with this hypothesis is the observation that carnitine increased flow during exercise of the muscle.

Animals↗

PubMed1991

Antibody response of humans to the circumsporozoite protein of Plasmodium vivax.

We studied the interaction of sera from residents of an area in northern Peru where vivax malaria is endemic with four recombinant DNA-derived circumsporozoite (CS) proteins of Plasmodium vivax. The antigens used in the enzyme-linked immunosorbent assay included one Escherichia coli-produced and three Saccharomyces cerevisiae-produced recombinant proteins. Three of the proteins (NS1(81)V20, Vivax-1, and Vivax-2) contain the entire central repeat region of the P. vivax CS protein, and one protein (Vivax-3) contains only two repeat sequences. Vivax-1, Vivax-2, and Vivax-3 contain different lengths of sequences flanking the repeats. A higher percentage of the sera had antibodies to Vivax-2 and Vivax-3, the two proteins containing the longest nonrepeat sequences, than to NS1(81)V20 or Vivax-1. Children less than 5 years of age did not have immunoglobulin G antibodies to NS1(81)V20; however, they had antibodies to Vivax-1, Vivax-2, and Vivax-3. The finding that individuals living in a malaria-endemic area produce antibodies to peptides containing nonrepeat regions of the CS protein emphasizes the need to characterize the immune response to these regions in naturally exposed and experimentally immunized humans.

Adolescent↗

PubMed1991

Acute effect of L-carnitine on skeletal muscle force tests in dogs.

Using the mixed type musculus latissimus dorsi of the dog in the present work, we show the effect of carnitine on an in situ fatigue test. L-Carnitine appears to improve force of this muscle by 34% while stimulated in situ. This effect of carnitine is acute and (stereo)specific, since neither D-carnitine nor the structural analogue choline (also a tertiary amine) has a positive effect on contractile force. Because skeletal muscle is rich in carnitine and because carnitine transport is slow, its effect must be exerted outside the striated muscle cells. Insulin (with glucose) administration abolished the carnitine effect. It is speculated that facilitation of fatty acid oxidation in the blood vessel wall is the basis for this positive effect of carnitine.

Blood Glucose↗