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J F Tomera

Publications and source records attributed to J F Tomera.

At least 37 records · Page 2Linked to original sources
PubMed1994

Multiple stepwise regression analysis of physiologic tension and secondary messengers in chronic burn trauma.

In this report, we have used a multiple stepwise regression analysis to determine the best derived multivariate equation between a dependent and multiple independent parameters. All parameters were derived from harvested gastrocnemius muscle subjected to chronic burn trauma. Correlations between seven different parameters were tested. Physiologic tension, calcium, adenosine 3':5' cyclic monophosphate (cAMP), inositol 1,4,5-triphosphate (IP3) and its catabolites comprised one large data matrix. From it, the various parameters were substituted as the dependent variable. The remaining parameters all comprised a multiple independent group. From such a format, the stepwise regression was run. The simultaneous co-governing of independent parameters over one dependent parameter provides a means of mathematically proving multiple correlations. Such findings provide a new perspective in interpreting chemical signalling.

Animals↗
PubMed1993

Myocardial [3H]polyinositol phosphates and their response to burn trauma.

Polyinositol phosphates comprise a portion of the phosphatidyl signal transducing system. The most well known is IP3 which stimulates Ca2+ release from Ca2+ sequestering organelles within cells. In this study, polyinositol phosphate changes in the heart subjected to the systemic effects of burn trauma were examined. The hypothesis was that systemic trauma induced by large body surface area (% BSA) burn may perturb the phosphatidylinositol signal transducing system. At postburn day 21 left ventricular tissues were harvested from mice with varying burn sizes (i.e. 0, 20 and 50 per cent). Levels of the polyinositol phosphates were measured by incorporation of myo-[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for statistical evaluation. Multivariate relationships between the independent polyinositol forms (inositol, Il,4P2 and I1P) existed for control (r2 = 0.71 and 50 per cent burn groups (r2 = 0.78). Numerous interdependent relationships existed within each of the multivariate tests. These analyses confirm that several independent polyinositol phosphates contribute to changes in the second messenger IP3 in ventricular tissue subjected to the systemic effects of burn trauma. Disruption of the polyinositol phosphates may underlie either the cause, or exacerbation, of heart dysfunction and cellular damage in burn patients.

Animals↗
PubMed1993

Changes in diaphragm polyinositol phosphates caused by a large body surface area burn.

Respiratory problems are common among burn patients, and an understanding of the changes that occur in the phosphatidyl inositol signal transducing system (s.t.s.) in diaphragm muscle may identify pharmacological agents that would be useful in the treatment of these patients. This report examines changes that occur in polyinositol phosphates of diaphragm muscle due to the systemic effects of large (> 30 per cent) body surface area (per cent BSA) burns. Burn injury was applied to specific per cent BSA of the dorsal and ventral skin surfaces of mice. At postburn day 21, polyinositol phosphate levels were measured in the diaphragm by the incorporation of myo-[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. All data were analysed using analysis of variance and curve fitting. In the diaphragm, levels of [3H]inositol, inositol-1,4,5 trisphosphate (IP3), inositol-1,4 bisphosphate (I1,4P2) and inositol-1 phosphate (I1P) increased with increasing burn size. Furthermore, a variety of independent relationships existed between the various phosphates in each burn group (i.e. control, 20 per cent and 50 per cent BSA burn). These data indicate that the systemic effects of burn trauma result in changes in the polyinositol phosphate part of the phosphatidyl inositol signal transducing system of diaphragm muscle.

Animals↗
PubMed1993

Multivariate influence of inositol phosphates on cAMP: interrelationships between signal transduction mechanisms in burn trauma.

The systemic effects of burn trauma impact on multiple systems of the body, affecting cell metabolism and function. This work examines the multivariate dependency of adenosine 3':5' cyclic monophosphate (cAMP) on three different forms of polyinositol phosphates in burn trauma. Burn injury was achieved by scalding predefined areas corresponding to 0, 20 and 50 per cent of the body surface area (BSA) on the dorsal and ventral surfaces of mice. At day 21, following twitch studies, cAMP levels in the gastrocnemius muscle were measured by 125I-labelled radioimmunoassay procedures. The levels of various polyinositol phosphates (inositol 1 phosphate (I1P), inositol 1,4 biphosphate (I1,4P2) and inositol 1,4,5 triphosphate (I1,4,5P3 or IP3)) were measured using myo-[2-3H]inositol. Through multivariate analysis, the dependency of cAMP was determined with respect to these three polyinositol forms as the independent factors. The contribution of each of these independent parameters was assigned to three-dimensional axes. Vector analysis determined the relationship of cAMP to each of the independent parameters in control, 20 per cent and 50 per cent burn groups. This vector analysis clearly illustrated the changing relationship that existed between the two signal transduction systems (sts) in control and burn groups. An understanding of these changing interrelationships may be useful in developing new means of treatment of a number of the systemic effects of burn trauma.

Animals↗
PubMed1993

Calcium and skeletal muscle: a multiple regression on signal transduction mechanisms in burn trauma.

The novelty of applying three-dimensional graphic capabilities involving area and vector changes was used to understand variations in inositol derivatives and their comodulating influence on calcium (Ca2+) in skeletal muscle under the duress of burn trauma. Burn injury was achieved by scalding of predefined areas (0, 20% and 50%) on the dorsal and ventral surfaces of mice. At day 21, 45Ca2+ influx and efflux procedures were performed. Through multiple regression, the dependency of intracellular Ca2+ was determined with respect to three polyinositol forms each representing independence simultaneously. The contribution of each of these parameters was assigned to a three-dimensional axis. Vector analysis determined the relationship of intracellular Ca2+ to each of the independent parameters in control, 20% and 50% burn groups. Such vector analysis allows for a clear visualization of the interrelationships that exist between secondary (viz, IP3) and tertiary (viz, Ca2+) messenger systems. This clear visualization may allow for a greater understanding of messenger systems that may lead to more effective treatment of the systemic effects of severe burn trauma.

Animals↗
PubMed1993

Multivariate influence of polyinositols on IP3 in diaphragm: individually applied matrix and vectorial analysis of trauma from small and large body surface area burn groups.

In this report, we have used multivariate and vectorial analyses to aid in understanding perturbations in diaphragmatic signal transduction in consequence to burn trauma. This trauma results from shock emanating from skin scald burn. Its respiratory complications are well-known. Relational matrices derived from experimental animal groups of varying body surface area (% BSA) burn size were subjected to individual multiple linear regression and vectorial analyses. Such individual matrices tested the simultaneous dependency of inositol 1,4,5-triphosphate (IP3) on inositol 1,4-biphosphate (I1,4P2), inositol 1-phosphate (I1P) and inositol. Understanding the contribution of multiple independent parameters simultaneously co-governing the dependency of IP3 offers new insight in regulating signal transduction mechanisms under the duress of burn trauma.

Analysis of Variance↗
PubMed1993

Cross-talk of second messengers during the systemic trauma response following burn injury: how, when, and where.

The systemic effects of trauma from large body surface area (% BSA) burns were evaluated in terms of second messenger levels involving polyinositol phosphates as they related to adenosine 3':5'-cyclic monophosphate (cAMP), myoplasmic Ca2+, and active tension. Gastrocnemius muscles were harvested after muscle twitch at postburn day 21. Levels of polyinositols were measured by incorporation of myo-[2-3H]-inositol, with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for statistical evaluation. Multivariate relationships between the: 1) independent polyinositol forms (3H-inositol, I1P, and I1,4,P2) and dependent I1,4,5,P3 existed for control (R2 = 0.71) and 20% BSA burn (R2 = 0.67) groups; 2) the independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent cAMP for control (R2 = 0.73), 20% BSA (R2 = 0.99), and 50% BSA (R2 = 0.99) groups; 3) independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent 45Ca2+ for the control (R2 = 0.99), 20% BSA (R2 = 0.44), and 50% BSA (R2 = 0.82) groups; and 4) independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent active tension for 20% BSA (R2 = 0.97) and 50% BSA (R2 = 0.64) burn groups. Numerous interrelationships existed with each of the multivariate tests. These analyses confirm that several independent polyinositols contribute to changes in the second messengers of I1,4,5,P3, cAMP, and Ca2+ in skeletal muscle as a result of the systemic trauma of burn injury.

Animals↗
PubMed1993

Multiple regression of skeletal muscle tension on inositol phosphates: cross-talk between signal transduction mechanisms in burn trauma.

Skeletal muscle weakness associated with burn trauma prolongs the time of rehabilitation of burn patients. Understanding the underlying chemical changes that impact on physiological tension may provide new therapeutic options for the treatment of burn patients. This report demonstrates the novelty of applying 3-dimensional graphic capabilities, involving area and vector changes to understand variations in inositol derivatives and their co-modulating influence on physiological tension in skeletal muscle. This muscle was distant from the primary anatomical burn site. It was subjected to circulatory shock emanating from burn trauma. Burn injury was achieved by scalding of predefined areas (0, 20% and 50%) on the dorsal and ventral surfaces of mice. At day 21, tension studies via muscle twitch analyses were performed. Through multiple regression, the dependency of physiologic tension was determined with respect to three poly-inositol forms each representing independent parameters simultaneously. The contribution of each of these parameters was assigned to a three-dimensional axis. Relationships of tension on three fixed independent parameters were found only for the 20% and 50% burn groups. Vector analysis on a plane in three-dimensional space determined the relationship of tension to each of the independent parameters in 20% and 50% burn groups. No significant relationship of tension dependency on three fixed poly-inositol variables was found in the control group. Such vector analysis, using solid and differential analytical geometry, allowed for a clear visualization of the interrelationships that existed between secondary messenger systems (viz, IP3) and a resulting physiologic manifestation (viz, tension). This clear visualization allows for a greater understanding of messenger systems that may lead to more effective treatment of skeletal muscle weakness associated with the systemic effects of severe burn trauma.

Animals↗
PubMed1992

Formation of gastrocnemius [3H]polyinositol phosphates in response to burn trauma.

The purpose of this report was to see if changes in polyinositol phosphates occurred with increasing percentage body surface area (% BSA) burn. Burn injury was applied to predefined areas of the dorsal and ventral skin surface of mice. After a 10-min stimulation period involving muscle twitch, polyinositol phosphate levels at 3 weeks postburn were measured by the incorporation of myo[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for all statistical evaluations. In gastrocnemius muscle an increase (P < 0.001) occurred for levels of [3H]inositol, inositol-1, phosphate (I1P), and inositol-1,4,5-trisphosphate (I1,4,5P3) for the 50 per cent BSA burn group. However, levels of inositol-1;4,biphosphate (I1,4P2) decreased (P < 0.001). Positive correlations were found between [3H]inositol, I1P and IP3 and 50 per cent BSA burn. A negative correlation between I1,4P2 and percentage BSA burn was found. These data provide evidence that polyinositol phosphate metabolism in skeletal muscle was altered due to large burn size.

Animals↗
PubMed1991

Gastrocnemius acetylcholinesterase activity in response to burn trauma in the mouse.

In this study we examined the effect of increasing size of body surface area (BSA, 20, 30 and 50 per cent) burn on distally located gastrocnemius acetylcholinesterase (AChE) activity. Burn injury was applied to predefined areas of the dorsal and ventral skin surfaces of mice. AChE activity at 3 weeks postburn was measured by differential extraction and velocity sedimentation on sucrose gradients. Analysis of variance was used for all statistical evaluation. Within the sham-treated controls most of the AChE activity consisted entirely (92 per cent) of the globular forms (S1 and S2). Asymmetric (S3 and S4) and non-extractable (H5) forms were 2 and 5 per cent, respectively. The total globular, asymmetric and non-extractable forms were not significantly different in gastrocnemius among the burn groups. However, individual forms (6.5S, 10S) of the soluble globular group (S1) were decreased (P less than 0.05) by half for all burn groups. Some molecular forms (4S, 10S) of residual globular group (S2) were decreased (P less than 0.05) in the 20 per cent and 50 per cent burn groups. In the asymmetric group (S3) the molecular forms (4S, 10S, 12S and 16S) were increased (P less than 0.001) for the 20 and 30 per cent groups. Within and between extraction groups interrelationships of the molecular forms were apparent. These data provide evidence that in response to burn trauma AChE activity of the gastrocnemius showed a decrease in soluble globular and an increase in asymmetric forms with multimeric dependence.

Acetylcholinesterase↗
PubMed1990

Thermal trauma alters myocardial cyclic nucleotides and protein content in mice.

1. This study tested the hypothesis that the systemic effects of burn include altered metabolic activity in the heart. Metabolic activity was studied by measuring alterations in cyclic nucleotide levels and protein concentrations in atrial and ventricular muscle in mice at 14 and 22 days after a 20% body surface area (BSA) burn. Thermal injury was produced on the dorsal surface of anesthetized male CD mice by immersion in water at 95 degrees C for 8 s. This resulted in a full-thickness, 3 degrees scald burn. In atrial and ventricular tissues, levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and guanosine 3':5'-cyclic monophosphate (cyclic GMP) were analyzed by 125I-radioimmunoassay. 2. The protein content (mg prot g-1 dry wt) increased in the atria. The cyclic AMP content (nmol g-1 dry wt) was significantly increased fourfold and ninefold at 14 and 22 days, respectively, in atria from burned animals compared to controls. The cyclic AMP/cyclic GMP ratios were similarly increased. 3. In the ventricle, the protein content and cyclic AMP levels were not altered, but the cyclic AMP/cyclic GMP ratios (nmol g-1 dry wt) were increased at both 14 and 22 days. These changes both in atria and ventricles were less prominent when cyclic nucleotide concentrations or ratios were expressed as pmol mg-1 protein. 4. The data confirm the hypothesis that a 20% BSA thermal injury evokes effects in sites remote from burn injury such as in the atria and ventricles. These effects include total body weight loss, elevated cyclic AMP, cyclic AMP/cyclic GMP ratios, and protein levels in the atria, and elevated cyclic AMP/cyclic GMP ratios in both atrial and ventricular tissues at 2 and 3 weeks after thermal injury. To prevent underestimation of cyclic nucleotide levels such changes should preferably be expressed on a prot g- dry weight basis.

Animals↗
PubMed1990

Effects of endotoxin infection on cyclic nucleotides in ventricular and gastrocnemius muscle.

The systemic effects of endotoxicosis were evaluated in terms of cyclic nucleotide levels within left ventricular and gastrocnemius tissue. Endotoxicosis was induced in mice by repeated intraperitoneal injection of Escherichia coli endotoxin on days 1, 7, and 14. Tissues were harvested at the end of 1 and 2 weeks of endotoxicosis. Levels of cAMP and cGMP were monitored by 125I-radioimmunoassay. There was a significant total body weight loss associated with markedly decreased cAMP levels in both ventricular (P less than 0.025) and gastrocnemius (P less than 0.025) muscle. The cGMP levels were unchanged in the ventricular muscle. When relationships between the cyclic nucleotides and total body weight loss were examined, differences were obtained between cAMP and cGMP. There was a direct correlation between increase in cGMP in the ventricular muscle and weight loss and an indirect correlation between decreased cAMP levels and weight loss. These relationships show that the respective role of each nucleotide was similar in each of the tissues. Furthermore, when the data were evaluated through multiple linear regression analysis, improved correlation coefficients were obtained. These analyses confirm that several independent factors contribute to the change in cyclic nucleotide metabolism in differing muscle types as a result of endotoxin infection.

Animals↗
PubMed1989

Mediators of burn-induced neuromuscular changes in mice.

1. Muscle paresis and aberrant pharmacological responses are two important pathophysiological changes that have been observed at the neuromuscular junction following thermal injury. By use of the mouse model of 20%, 30% and 50% total body surface area (BSA) burn, we examined the significance of intracellular mediators, adenosine 3':5'-cyclic monophosphate (cyclic AMP) and prostaglandin E2 (PGE2) in perturbing the physiological function of tension development and the pharmacological response to (+)-tubocurarine (+)-Tc at day 21 post-burn. 2. Cyclic AMP levels increased with the size of burn. The relationship between mean cyclic AMP levels and burn size was significant (R2 = 0.96, r = 0.98). Significant (P less than 0.05) reductions in tension development (g) were observed for the 30% and 50% BSA burn group compared to controls (30.3 +/- 8.3 and 34.1 +/- 5.9 vs 59.1 +/- 1.0, respectively). Tension alterations were associated with increased cyclic AMP levels; the relationship between increased cyclic AMP levels and tension decrease was significant (R2 = 0.82, r = 0.91). The dose of (+)-Tc required to inhibit twitch tension increased in proportion to burn size and was statistically significant in the 50% BSA burn group compared to controls (0.3320 +/- 0.09 vs 0.1093 +/- 0.11 mg kg-1, P less than 0.05). The alterations in the effective dose of (+)-Tc were significantly correlated to increases in cyclic AMP levels (R2 = 0.70, r = 0.83). Although PGE2 levels were elevated in the 30% and 50% burn groups, no relation was seen to either tension or (+)-Tc doses. 3. These studies, therefore, support the hypothesis that cyclic AMP plays a significant role in physiological and pharmacological responses in skeletal muscle following thermal injury.

Animals↗
PubMed1989

Intraperitoneal endotoxin but not protein malnutrition shifts d-tubocurarine dose-response curves in mouse gastrocnemius muscle.

Burn injury-induced changes at the neuromuscular junction include muscle weakness and altered response to neuromuscular blocking drugs. Protein malnutrition and sepsis can concomitantly occur with burn trauma. The role of pure malnutrition or sepsis, in the absence of burn injury, in inducing neuromuscular changes was studied in the mouse gastrocnemius muscle. Additionally, cAMP levels in muscle were evaluated to reflect metabolic activity. Sepsis was studied using doses of endotoxin at one-fourth or one-third the dose evoking 50% lethality. Diets of 5% protein and 5% protein + 35% fiber achieved protein and protein/calorie malnutrition, respectively. In each model neuromuscular function was evaluated by maximal tension developed. Pharmacologic responses were measured through effective dose to paralyze active tension by either 50 or 95%. Protein and protein/calorie malnutrition leading to an approximate 8% body weight loss caused a depression of maximal tension developed; this depression in tension was associated with a 10-fold increase in cAMP levels. Effective doses of d-tubocurarine for twitch inhibition during malnutrition were not significantly different from controls. Sepsis at 2 weeks caused an approximate 8% body weight loss, a significant decrease in maximal tension and at least a 3- to 5-fold shift to the right in dose-response curves to d-tubocurarine. In contrast to malnutrition, cAMP levels were significantly decreased (P less than .001) in sepsis to 1/400 of controls. The altered neuromuscular function and pharmacology observed in sepsis are similar to changes observed in burn injury. Protein malnutrition common to these two states may be important in functional but not pharmacological changes at the neuromuscular junction.

Animals↗
PubMed1988

Systemic effects of single hindlimb burn injury on skeletal muscle function and cyclic nucleotide levels in the murine model.

This study tested the hypothesis that a single hindlimb burn has both local and distant effects. Male CF1 anaesthetized mice were given a full thickness scald burn of 3 per cent total body surface area (BSA) by immersion of their left hindlimb in water at 95 degrees C for 5 s. Muscle tension was measured through twitch analysis. Levels of cyclic adenosine 3'-5' monophosphate (cAMP) and cyclic guanosine 3'-5' monophosphate (cGMP) were analysed by 125I-radioimmunoassay. Measurements were made in gastrocnemei of the ipsilateral burned and contralateral unburned limbs over a 28-day postburn period. Within 1 week the burned limb showed an increase in both tension and a 100-fold increase in levels of cAMP. However, by the end of the second week muscle tension in the burned limb dropped to one-seventh of control values despite persistence of high levels of cAMP. In contrast, the systemic effects were manifested in the unburned contralateral limb which showed tension to undergo a six-fold compensatory increase at the end of the second week with a 75-fold increase in cAMP. By the end of 4 weeks, tension levels of both burned and unburned limbs were attenuated to one-half control values indicating neuromuscular (NM) dysfunction. Nevertheless, cAMP levels remained elevated in both limbs. Levels of cGMP were reduced throughout the 4-week postburn period. Subsequent to the single hindlimb injury both ipsilateral and contralateral gastrocnemei muscles showed elevated levels of total protein content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Azathioprine fails to alter the dose-response curve of d-tubocurarine in rats.

Cyclic 3':5' adenosine monophosphate (cAMP) mediated facilitation of neuromuscular (NM) transmission was previously implicated in the mechanisms of the reversal of nondepolarizing NM relaxants by azathioprine (AZA). This interaction of d-tubocurarine (dTC) with AZA was re-examined in rats and correlated to changes in cAMP in the same muscle. Three groups of animals were studied: controls, low-dose AZA (5 mg/kg), and high-dose AZA (50 mg/kg). After AZA or saline administration, dose-response (DR) curves for inhibition of gastrocnemius twitch tension by dTC were constructed. Contralateral gastrocnemius muscle was sampled for cAMP levels. In another group of animals, the response to 5- and 50-mg/kg boluses of AZA was recorded during a steady-state twitch depression maintained with an infusion of dTC. No significant shift in the DR curve of dTC was observed following low- and high-dose AZA. During steady-state twitch depression, high-dose AZA, however, caused a transient reversal of twitch lasting 5-10 min. High-dose AZA caused a significant (P less than 0.006) elevation of cAMP levels (340 +/- 49 pmol/mg prot) compared to control (120 +/- 18) and low-dose (163 +/- 24) AZA groups. These studies, therefore, document transient reversal of twitch tension by 50 mg/kg doses of AZA during a steady-state dTC infusion. On the other hand, AZA administered prior to dTC in low (5 mg/kg) and high (50 mg/kg) doses failed to cause a significant shift in the dTC DR curve. A three-fold increase in skeletal muscle cAMP induced by high-dose AZA does not alter dTC DR curves.

Animals↗
PubMed1988

Neuromuscular dysfunction in burns and its relationship to burn size, hypermetabolism, and immunosuppression.

The etiology of neuromuscular (NM) dysfunction following burn injury has not been characterized. NM deficits, together with hypermetabolism and immunosuppression, are debilitating processes which play a key role in the morbidity and mortality of burned patients. This study examined the usefulness of the murine model to replicate clinically observed NM dysfunction. Systemic effects of graded increases in burn size were studied in the acute phase (3 weeks) of burn trauma. Metabolic rates, immune response to dinitrofluorobenzene (DNFB), maximum tension developed by gastrocnemius muscle, and the response of its NM junction to d-tubocurarine (dTc) were the parameters analyzed. Groups of male CF1 mice were given a 20%, 30%, and 50% total body surface area burn and compared to controls. By Day 21 postburn, all the burn groups showed elevated metabolic rates and immunosuppression to the inflammatory antigen DNFB. NM dysfunction evidenced as a significant depression of maximal tension development was observed in the 30% and 50% groups. A threefold increase in the effective dose (ED95) values of dTc was seen only in the 50% burn group. No NM junctional changes were seen in the 20% burn group. These findings are consistent with clinical observations. We conclude that the mouse is a useful model for evaluating NM dysfunction of burns.

Animals↗