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Biomedical subjects

J L Moore

Publications and source records attributed to J L Moore.

At least 19 recordsLinked to original sources

Thermodynamics of cyclic nucleotide binding to the cAMP receptor protein and its T127L mutant.

The thermodynamics of the binding of cyclic adenosine monophosphate (cAMP) and its non-functional analog, cyclic guanosine monophosphate (cGMP), to cyclic AMP receptor protein (CRP) and its T127L mutant were investigated by isothermal titration calorimetry (ITC) in 0.2 and 0.5 M KCl phosphate buffer (pH 7.0) at 24 and 39 degrees C. Although, the binding of the first cAMP molecule to CRP is exothermic with an enthalpy change (delta Hb) of -6 kJ mol-1, a heat capacity change (delta Cp) of -0.300 kJ mol-1 K-1, and an entropy increase (delta Sb) of 72 J mol-1 K-1, the overall binding of cAMP to CRP is endothermic and positively cooperative: binding of the first cAMP molecule increases the affinity for the second one by more than an order of magnitude at 24 degrees C. The binding of the second cAMP molecule is accompanied by large changes of 48.1 kJ mol-1 in delta Hb, of -1.4 kJ mol-1 K-1 in delta Cp, and of 255 J mol-1 K-1 in delta Sb at 24 degrees C and 0.5 M KCl phosphate buffer. In contrast, the overall binding of cGMP to CRP is exothermic and non-cooperative with delta Hb, delta Cp, and delta Sb values close to the those values for binding of the first cAMP molecule to CRP. The point mutation, T127L, switches off the cooperativity between the cAMP ligated binding sites without affecting the binding constant of cAMP and changes the specificity of the protein so that transcription is now activated only upon cGMP binding. All the binding reactions to CRP and the mutant are mainly entropically driven at 24 degrees C.

Amino Acid Sequence

Clinical activity of leukotriene inhibitors.

Data from the emerging clinical trials with compounds such as zileuton, ICI 204,219, Bay X1005, MK571, MK679, and MK591 are demonstrating the importance of the leukotrienes as mediators of asthma and possibly other diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. One of the major questions facing the asthma community is how much improvement in the FEV1 is needed to improve the quality of life of the asthmatic patient. Comparing the various approaches to asthma treatment, there is typically 15-20% improvement in the lung function with inhaled steroids. Leukotriene interventions apparently will improve lung function to similar levels as with inhaled steroids, and thus may offer an alternative to steroids. Like the steroids, zileuton appears to also reduce the inflammatory cell influx into the antigen-challenged site, which may have the long-term effect of reversing some of the tissue alterations that occur as a result of the inflammation seen with asthma. Importantly, the reported experience to date has shown that the leukotriene modulators do not have the same side-effects as the current therapies, and thus offer the hope that both safe and effective treatment may be derived from this approach. The clinical data reported do not yet define a preferred approach to the modulation of leukotriene pathology. As more studies are published in other diseases the broad spectrum use of these inhibitors will become known.

Anti-Inflammatory Agents

Upper extremity injuries related to airbag deployments.

OBJECTIVE: Details on airbag injuries to the upper extremity are relatively unknown to clinicians. The injuries presented here should provide a clear understanding of the mechanisms of forearm, hand, and wrist injuries that may be seen by emergency room physicians. MATERIALS AND METHODS: From our crash investigations of 325 airbag-equipped passenger cars, a subset of upper extremity injuries are presented that are related to airbag deployments. MAIN RESULTS: Minor hand, wrist, or forearm injuries--contusions, abrasions, and sprains--are not uncommonly reported. Infrequently, hand fractures have been sustained and, in isolated cases, fractures of the forearm bones or of the thumb, wrist, and fingers. The close proximity of the forearm to the airbag module door is related to most of the fractures identified. Steering wheel airbag deployments can fling the hand-forearm into the instrument panel, rearview mirror, or windshield, as indicated by contact scuffs, tissue debris, or the star burst (spider web) pattern of windshield breakage in fron of the steering wheel. CONCLUSION: Minor injuries of the upper extremity can occur when contacted by the deploying airbag either directly or by flinging the hand-forearm into interior car structures. Fractures of the forearm are rare and usually are due to direct impact by the forceful opening of the airbag module door.

Accidents, Traffic

Effect of blood transfusion in patients with gynecologic malignancy.

OBJECTIVES: To determine the effect of blood transfusion on long-term outcome (disease-free interval, recurrence of disease after treatment, and survival) in women with invasive gynecologic malignancy. METHODS: In this retrospective study, 125 patients with gynecologic malignancy were assessed over a 36-month period. The variable of whether patients received blood transfusion during therapy was used to divide the sample into two groups. RESULTS: There were no differences in the age, ethnicity, and site-stage of tumor of the two groups. Treatments (surgery, radiotherapy, chemotherapy, or multimodal) were similar between the two groups, as were initial hematocrits. The disease-free interval was significantly better in women who did not receive homologous blood (P < 0.001). Life table analysis illustrated that more patients were alive and free of disease if they did not receive blood (P < 0.001). Likewise, persistence-recurrence of cancer was more common in the transfusion group (P < 0.001). Finally, overall survival time was adversely affected by transfusion (P = 0.045). CONCLUSIONS: The use of blood products in patients with invasive gynecologic cancer is associated with enhanced recurrence or persistence of malignancy, a decrease in the disease-free interval, and reduction in the probability of survival without evidence of disease.

Adult

EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness.

Subtypes of status epilepticus (SE) without tonic-clonic convulsions (nontonic-clonic SE) present as altered consciousness sometimes with subtle motor activity and are important to consider in the differential diagnosis of patients with unexplained altered consciousness. Other patients may have altered consciousness with intermittent ictal activity on electroencephalography (EEG) that represents probable SE, but have other medical conditions that may be contributing to altered consciousness. EEG is the only reliable way to make the diagnosis of nontonic-clonic SE and we make emergency EEG available on a 24-h basis at our hospital. To determine how often definite or probable nontonic-clonic SE was detected by EEG we prospectively collected data on all cases where physicians ordered EEG to evaluate altered consciousness or possible SE. Out of 198 cases with altered consciousness but no clinical convulsions, 74 (37%) showed EEG and clinical evidence of definite or probable nontonic-clonic SE. Forty-two episodes (57%) were probable or definite complex partial SE, 29 (39%) were probable or definite subtle generalized SE, and three (4%) were myoclonic SE. In 23 SE cases altered consciousness was the only clinical sign at the time of diagnosis; subtle motor activity was present in 36 others. Neither clinical signs nor prior history predicted which patients showed SE on EEG. Nontonic-clonic SE followed a cerebral infarction in 16 cases. Contrary to other reports, we found no relationship between duration of SE and EEG pattern. Subtle generalized SE occurred most commonly in the setting of a diffuse brain injury rather than evolving from convulsive SE. This study demonstrates that nontonic-clonic SE is a common finding in patients with unexplained altered consciousness and EEG is necessary in the evaluation of these patients.

Adolescent

Field investigations of the performance of air bag deployments in frontal collisions.

This paper documents field investigations of "air bag" crashes selected from a large group of air bag crashes in file at the University of Michigan Transportation Research Institute (UMTRI). A full range of crashes are presented with injury levels of AIS 1-2 to AIS 5-6. Most occupants sustained minor injuries. Those not wearing the lap-shoulder belt (3-point belt) had more minor injuries than the restrained. The occurrence of higher level injuries (AIS > or = 2) was found more often in the nonbelted.

Accidents, Traffic

A case of chronic depression.

The authors describe a case of chronic depression in a designated Naval Aviator with a concomitant history of hypothyroidism. The differential diagnosis of dysthymia is discussed and the associated therapeutic alternatives are reviewed. The case demonstrates the importance of comprehensive physical and psychiatric evaluation of those patients with complex or atypical presentations. Issues pertaining to the aeromedical disposition of such patients are discussed, with emphasis on the role of the flight surgeon.

Adult

Isolation and structural analysis of the rat MyoD gene.

We have cloned and determined the nucleotide (nt) sequence of a 6.5-kb genomic DNA fragment containing the rat MyoD gene (encoding a muscle regulatory factor, MyoD). Mouse fibroblasts transfected with this DNA display a high degree of conversion to a muscle phenotype, suggesting that this genomic clone contains sufficient sequence information to allow the production of the rat MyoD protein in these cells. The 6.5-kb genomic fragment contains the complete coding region of MyoD, distributed over three exons, plus 2.3 kb of 5'-noncoding sequence and 1.4 kb of 3'-noncoding sequence. Based on RNase protection assays, the major transcription start point of MyoD is located 210 nt 5' to a methionine start codon and 26 nt 3' to a TAAATA motif which bears similarity to a consensus recognition sequence (TATA) utilized by eukaryotic RNA polymerase II transcription complexes. The high degree of identity between the amino acid sequence of rat MyoD and the MyoD proteins isolated from other vertebrates indicates that this muscle regulatory protein has been evolutionarily conserved.

Amino Acid Sequence

Adjunctive antibiotic treatment of women with preterm rupture of membranes or preterm labor.

Subclinical infection is associated with preterm rupture of the membranes (PROM) and preterm labor (PTL) in many cases. It was hypothesized that antibiotic treatment might delay delivery and/or decrease infectious morbidity in those with PROM or PTL. Patients from 19 to 34 weeks with PROM and no labor or PTL with intact membranes (but not both) were separately randomized to receive ampicillin versus placebo in addition to usual therapy. There were 36 women with PTL (21 ampicillin/15 placebo) and 84 with preterm PROM (41 ampicillin/43 placebo). Demographically, the treatment and placebo groups were similar. Outcome variables analyzed included delivery delay after treatment, maternal chorioamnionitis/endometritis, Apgar score, neonatal infection, or respiratory distress, and hospital stay. There were no significant differences between the ampicillin and placebo groups in those with PTL or preterm PROM as it concerned outcome parameters. Adjunctive ampicillin used for treatment of idiopathic PTL or preterm PROM was not beneficial in this study.

Adult

Zidovudine-interferon-alpha combination therapy in patients with advanced human immunodeficiency virus type 1 infection: biphasic response of p24 antigen and quantitative polymerase chain reaction.

In an open-label dose-ranging pilot trial, 13 homosexual men with human immunodeficiency virus type 1 (HIV-1) p24 antigenemia after at least 6 weeks of zidovudine monotherapy were continued on zidovudine and given interferon-alpha, 1.25-7.5 x 10(6) units/m2 subcutaneously three times/week. Plasma p24 antigen levels demonstrated a biphasic response, falling initially in 11 patients by a mean of 50% (95% confidence interval, 36%-64%; P = .001) at a median of 11 weeks, but rising steadily thereafter (P = .001). CD4+ cell counts fell by a mean of 7.1 cells/mm3/week (P = .01). Higher initial CD4+ counts predicted greater p24 antigen reductions. At higher interferon doses no greater reductions in p24 antigen occurred, but side effects were more severe and CD4+ lymphocyte counts fell faster. Polymerase chain reaction quantification of HIV-1 DNA in 3 patients showed a biphasic pattern paralleling the p24 antigen response. In sum, although evidence of short-term effects was found, the combination showed no evidence of lasting antiviral activity beyond that achieved with zidovudine alone in patients with advanced HIV-1 infection.

AIDS-Related Complex

Air bag injuries and occupant protection.

Analysis of the investigations of crashes involving automobiles equipped with air bags verifies the estimations of the lifesaving and injury reduction benefits of this supplemental restraint system. Cases of air bag-associated injuries, primarily erythema, abrasions, and contusions of the lower face and anterior throat-upper chest, are identified as those most often observed. Corneal-scleral injuries were infrequently noted but are rarely found in crashes involving air bag deployments.

Accidents, Traffic

Cancer and pregnancy.

The diagnosis of cancer rarely complicates pregnancy. Despite the fact that advanced disease is often encountered, there is no scientific evidence that the pregnant state alters the neoplastic process. Only through careful attention to the patient can the clinician detect cancer at an early stage and offer the patient reasonable hope for a cure.

Female

Identification and categorization of the vascular patterns to muscles of the thoracic limb, thorax, and neck of dogs.

Vascular patterns to thoracic limbs, thorax, and neck muscles were studied in 10 dogs (20 limbs) to identify muscles most suitable for transposition in the treatment of large wounds. Gross dissection of injected specimens and angiography were used to identify vascular pedicles. Size and location of pedicles were generally consistent, and any variations would not interfere with most muscle transfers. The cutaneous trunci, latissimus dorsi, sternothyroideus, sternohyoideus, deep pectoral, anconeus, ulnaris lateralis, and ulnar head of flexor carpi ulnaris muscles were identified as suitable for transfer. The cranial trapezius, caudal omotransversarius, cleidobrachialis, and caudal sternocephalicus muscles also had potential for use. Other muscles, because of inaccessibility or unfavorable vascular pattern, were not suitable candidates for transfer.

Animals

Malignant hyperthermia.

Malignant hyperthermia is a rare syndrome that occurs in genetically susceptible individuals who are exposed to frequently used inhalation anesthetics. The disorder is most common in children and young adults. It is triggered through a defect in the ability of skeletal muscles to concentrate and release calcium. Signs of malignant hyperthermia include hypercarbia, muscle rigidity and tachycardia. Temperature elevation is often a late sign of the syndrome. Treatment begins with stopping all inhaled anesthetics at the earliest sign of the syndrome. The use of dantrolene has significantly reduced mortality from malignant hyperthermia. No simple screening test exists. Family members or those with a suspicious history need to be counseled and should consider muscle biopsy and testing prior to surgery.

Adult