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Biomedical subjects

J L Moore

Publications and source records attributed to J L Moore.

At least 37 records · Page 2Linked to original sources

Hearing loss and automobile airbag deployments.

In an on-going research program, on the causation of injuries in motor vehicle accidents, at the University of Michigan Transportation Research Institute, crashes with airbags have been, and are continuing to be, investigated. In order to determine the occurrence, if any, of 'hearing problems' associated with airbag deployments, drivers and passengers who had been involved in 'airbag' automobile crashes were interviewed by telephone. From the crashes investigated, 225 attempts were made to contact drivers who were exposed to airbag deployments. From these telephone interviews, contacts were made with 177 car occupants. Only three reported that they had experienced any type of hearing-related problems subsequent to their crash. One other case is reported of a driver who had pre-crash hearing loss. It appears that permanent hearing deficit due to airbag deployment, both in cars with the steering wheel airbag alone, and in those with a passenger side airbag, is an infrequent event (1.7%) from the data of this study.

Accidents, Traffic↗

Arachnoid cysts: how do postsurgical cyst size and seizure outcome correlate?

Arachnoid cysts (ACs) are congenital cystic brain malformations associated with epilepsy. The purpose of this study was to determine the effect of surgical intervention of ACs on cyst size and seizure outcome. We reviewed the world's medical literature dealing with surgically treated ACs in epilepsy patients. Our study included only cases, in which the relationship between pre-and postoperative CT-size of the AC and seizure outcome was described. We also included six patients with ACs and epilepsy treated surgically at the University of Mainz. We analyzed postoperative AC size and seizure outcome with respect to mode of operation, cyst location, and patients' age. A total of 76 patients was reviewed. Sixty (79%) patients had a smaller AC postoperatively. Forty-six of those 60 (76.6%) experienced seizure improvement. Thirteen patients (21.6%) remained unchanged and one patient (1.8%) worsened. In 16 of the 76 patients (21%) the postoperative AC size was unchanged. Eight of those 16 patients improved. Six patients (37.5%) remained unchanged and two (12.5%) worsened. A positive correlation between postoperative AC size and seizure outcome was well demonstrated among patients treated by cyst fenestration, needle aspiration, or internal shunting. Among patients treated by cystoperitoneal shunting this direct correlation was less clear. Seizure outcome correlates directly with postoperative AC size. Seizure reduction is associated with decreased AC size postoperatively and depends on the mode of operation. Based on these data we would expect that patients with epilepsy secondary to ACs would demonstrate improved seizure control with lower AC volume. Conversely, we might expect increasing AC size to correlate with worse seizure control. This relationship may guide physicians in efficacy and timely patient management.

Adolescent↗

Fenestration of porencephalic cysts to the lateral ventricle: experience with a new technique for treatment of seizures.

BACKGROUND: Porencephalic cysts are brain cavities resulting from perinatal vascular occlusion and are commonly associated with severe neurological deficits and medically intractable epilepsy. Thirty-seven children presenting to the University of Münster with intractable seizures because of a porencephalic cyst were treated by uncapping and fenestration of these cysts to the lateral ventricle between 1978 and 1992. We conducted the following study to determine the efficacy and safety of the uncapping and fenestration procedure for the treatment of seizures. METHODS: We reviewed all cases retrospectively and assessed the outcome of these patients with regard to seizures, paresis, and perioperative complications. RESULTS: Of 37 children, 23 (62%) were seizure-free postoperatively. Nine patients (24%) had a reduction of seizures and five children (14%) remained unchanged. Of 30 patients with preoperative hemiparesis, 11 (30%) improved after the operation. The leading postoperative problem was a subcutaneous/subgaleal cushion of CSF, which affected 12 children (12 of 37). A dural patch covering the iatrogenic dural defect could not prevent or reduce postoperative CSF leakage, but prolonged the postoperative fever period. Postoperative fever occurred in 36 children (36 of 37) and was caused by an aseptic meningitis. CONCLUSIONS: Children with intractable seizures and porencephalic cysts benefit from uncapping and cyst fenestration to the lateral ventricle. Concomitant perioperative complications are mild and are easily treated.

Adolescent↗

Amnioinfusion-induced malpresentation.

Amnioinfusion is a valuable and common intrapartum procedure for the relief of cord compression and to dilute thick meconium. Like most procedures, it is not without risk and we report a case of malpresentation following amnioinfusion. Intrapartum fetal demise occurred after malpresentation during amnioinfusion resulting in a change of fetal presentation from vertex to unrecognized shoulder presentation. Further study is needed regarding changes in volume of amniotic fluid and saline as well as intrauterine manipulation and the effect on fetal presentation. Careful attention must be paid to infused volumes during amnioinfusion.

Adult↗

A descriptive analysis of "not aeronautically adaptable" dispositions in the U.S. Navy.

BACKGROUND: All aviation personnel in the U.S. Navy are evaluated for aeronautical adaptability (AA) in both initial and periodic examinations and for daily aeromedical disposition. By definition, all aviation personnel with a diagnosed personality disorder or those with maladaptive personality traits that have had a documented effect on safety of flight, crew coordination, or mission completion, are determined to be Not Aeronautically Adapted (NAA). METHODS: NAA dispositions were examined for demographic data, basis for disposition, and frequency of personality features. RESULTS: NAA dispositions were made on the basis of personality disorders and maladaptive personality traits in 29% and 35% of the cases, respectively. The officer and enlisted NAA dispositions were distinctly different in terms of frequency of personality features. Obsessive-compulsive features were present in 58% of officer and 10% of enlisted NAA dispositions. Dependent and avoidant features were present in excess in comparison to psychologically healthy aviators, suggesting the incompatibility of these features with aviation.

Adaptation, Psychological↗

Activation of the focal adhesion kinase signal transduction pathway in cervical carcinoma cell lines and human genital epithelial cells immortalized with human papillomavirus type 18.

The inappropriate activation of protein-tyrosine kinases (PTKs) has been associated with initiation and progression of several types of human cancers. We therefore postulated that immortalization by DNA tumor viruses results in the induction of PTKs fundamental to these processes. An RT-PCR-based screen was thus used to identify PTKs that were abundantly expressed in HPV-18-immortalized epithelial cells and HPV-containing carcinoma cell lines. One of the genes isolated in this screen was the focal adhesion kinase (FAK; pp125FAK), a cytoplasmic protein kinase that is activated in v-src transformed cells or by stimulation with mitogenic polypeptides. FAK also becomes catalytically active upon integrin engagement with extracellular matrix proteins, such as fibronectin. We found that FAK expression and activity were significantly elevated in HPV-18 E6/E7-immortalized human genital epithelial cells relative to their primary cell counterparts. Protein expression and tyrosine phosphorylation of the putative FAK substrate, paxillin, were also notably increased upon HPV-18 immortalization of genital epithelial cells and in HPV-containing cervical carcinoma cell lines. Most significantly, these cells expressed markedly higher levels of both intracellular and extracellular fibronectin, thus providing a mechanism for activation of FAK and increased tyrosine phosphorylation of paxillin. These findings suggest a role for the integrin/FAK-mediated signaling pathway in cervical carcinogenesis and represent one of the first demonstrations of a tyrosine kinase whose activity is elevated following viral immortalization.

Cell Adhesion Molecules↗

Structure-activity relationships of N-hydroxyurea 5-lipoxygenase inhibitors.

The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hydroxyure a (17c) was identified and selected for clinical development.

Animals↗

Panic with a twist: an unusual presentation of combined psychiatric and neurologic symptoms in a tactical jet aviator.

A 28-yr-old Naval F-14 aviator presented with complaints of flight-related anxiety occurring intermittently over an 18-mo period. Symptoms included sensation of strangeness, concern over the welfare of his radar intercept officer, flushing, nausea, and intense need to immediately land the aircraft. He also described a 6-mo history of episodes wherein he would see "shooting stars" in the periphery of his vision, accompanied by dizziness and disorientation. These latter attacks were always precipitated by head turning, usually in combination with positive Gz maneuvers, and were relieved by head straightening. The anxiety symptoms were consistent with a form of panic attack, but the neurological symptoms provoked further workup. Magnetic resonance cerebral angiogram demonstrated a dominant right vertebral artery and hypoplastic left vertebral artery. All symptoms resolved once the aviator was removed from flying the aircraft. After a year of follow-up with an aviation psychiatrist, he remained asymptomatic and was reassigned to maritime patrol aircraft. This case illustrates a difficult diagnostic, therapeutic, and disposition challenge. This aviator suffered from a complex interaction of neurologic and psychiatric manifestations having a common inciting stimulus, namely flying the F-14 Tomcat. A promising aviation career was preserved upon removal of that stimulus.

Adult↗

Lifelong self-directed learning using a computer database of clinical questions.

Physicians often have self-perceived knowledge gaps when they are seeing patients. Traditional continuing medical education is designed to meet the knowledge gaps of groups rather than individual physicians with specific patient problems. Physicians with clinical information needs are advised to critically evaluate high-quality original research in order to practice "evidence-based medicine." But this advice may be unrealistic for busy clinicians. We propose a system for documenting self-perceived information needs using a computer database. Concise answers to these needs are included in the database along with reference citations supporting the answers. The system tracks continuing education efforts, directs patient care decisions, and focuses lifelong learning on relevant topics. We emphasize the importance of being sensitive to personal information needs and the benefits of maintaining a record of these needs.

Clinical Medicine↗

Genetic dissection of vertebrate processes in the zebrafish: a comparison of uniparental and two-generation screens.

Genetic dissection is used to identify important genes in biological processes and is accomplished through the generation and study of mutations in model organisms. In diploid organisms, recessive mutations must be rendered hemizygous or homozygous for the mutant phenotype to be detected. In zebrafish (Danio rerio), this can be accomplished in two ways: (i) crosses between siblings who are potential carriers (in two-generation screens) and (ii) the generation of uniparental progeny. Two-generation screens have been the most productive to date but require substantial resources. However, uniparental screens involving haploids and half-tetrads (products of meiosis I) have also been productive, and require more modest resources. In genetic screens, the fraction of an average genome that is heterozygous (heterozygosity index) is inversely proportional to the likelihood that separate recessive mutations will be homozygous at the same time. Heterozygosity indices for haploid, half-tetrad, and two-generation screens are 0, 66, and 87.5%, respectively. Family sizes required to minimize bias in half-tetrad screens are also calculated. We conclude that gynogenetic half-tetrad screens are genetically robust and technically accessible to the independent researcher. The increasingly powerful genetic and experimental tools available for work with zebrafish can be used to address a broad range of questions in vertebrate biology.

Animals↗

Effect of cAMP binding site mutations on the interaction of cAMP receptor protein with cyclic nucleoside monophosphate ligands and DNA.

Although cAMP binding to wild type cAMP receptor protein (CRP) induces specific DNA binding and activates transcription, cyclic nucleoside monophosphate (cNMP) binding to the CRP mutant Ser128 --> Ala does not, whereas the double CRP mutant Thr127 --> Leu/Ser128 --> Ala activates transcription even in the absence of cNMP. Isothermal titration calorimetry measurements on the cNMP binding reactions to the S128A and T127L/S128A mutants show that the reactions are mainly entropically driven as is cAMP binding to CRP. In contrast to cAMP binding to CRP, the binding reactions are noncooperative and exothermic with binding enthalpies (DeltaHb) ranging from -23.4 +/- 0.9 kJ mol-1 for cAMP binding to S128A at 39 degrees C to -4.1 +/- 0.6 kJ mol-1 for cAMP binding to T127L/S128A at 24 degrees C and exhibit enthalpy-entropy compensation. To account for the inactivity of the S128A mutant, in vitro and in vivo DNA binding experiments were performed on the cAMP-ligated S128A mutant. The cAMP-ligated S128A mutant binds to the consensus DNA binding site with approximately the same affinity as that of cAMP-ligated CRP but forms a different type of complex, which may account for loss of transcriptional activity by the mutant. Energy minimization computations on the cAMP-ligated S128A mutant show that amino acid conformational differences between S128A and CRP occur at Ser179, Glu181, and Thr182 in the center of the DNA binding site, implying that these conformational changes may account for the difference in DNA binding.

Binding Sites↗

Recurrent granulosa cell tumor of the ovary 37 years after initial diagnosis: a case report and review of the literature.

Granulosa cell tumors of the ovary (GCTs) are uncommon neoplasms that are characterized by late recurrence and high survival rates. A case of recurrent GCT presenting 37 years after initial diagnosis is reported with a review of the literature. This case illustrates an example of a very late recurrence and emphasizes the importance of the extended follow-up required for these patients.

Aged↗

Periodic lateralized epileptiform discharges in multiple sclerosis.

We report an unusual cause of periodic lateralized epileptiform discharges (PLEDs) in a young man with a long history of multiple sclerosis. Two exacerbations of multiple sclerosis, 3 years apart, were complicated by complex partial status epilepticus. After each episode, serial electroencephalograms revealed PLEDs (right frontal PLEDs in the first episode and right frontotemporal and bifrontal PLEDs in the second one), which resolved within 2 weeks. With the first episode, magnetic resonance imaging revealed an enhancing white matter lesion in the right frontal area, which improved after 3 weeks. We concluded that in each instance an exacerbation of multiple sclerosis caused the seizures.

Adult↗

Endometrial stromal sarcoma with focal smooth muscle differentiation: recurrence after 17 years: a follow-up report with discussion of the nomenclature.

In 1977, a case report was published describing a 28-year-old women with an endometrial stromal tumor that showed foci of myogenic differentiation. The term "stromomyoma" was introduced to encompass both this type of neoplasm as well as "uterine neoplasms resembling ovarian sex-cord tumors" (UTROSCTs). More than 17 years later, the tumor recurred, involving the right ovary, sigmoid colon, small bowel, abdominal wall and omentum. The histologic and electron microscopic similarities between the recurrent tumor and the primary neoplasm were confirmed. Applying the recent classification and diagnostic criteria of endometrial mesenchymal neoplasms, we have concluded that this tumor was a low-grade endometrial stromal sarcoma (LGSS). The formerly proposed term "stromomyoma" implies a benign tumor, in contrast to the obviously malignant nature of this particular tumor. Focal myogenic differentiation of LGSS is not an uncommon finding and does not warrant a separate diagnostic or prognostic entity. UTROSCTs and endometrial stromal sarcomas are two separate diagnostic entities, and combining them under an inclusive terminology is not appropriate.

Abdominal Neoplasms↗

The rev-responsive element negatively regulates human immunodeficiency virus type 1 env mRNA expression in primate cells.

The human immunodeficiency virus type 1 (HIV-1) Rev protein mediates the accumulation of unspliced and singly spliced viral transcripts within the cytoplasm of infected cells, late in the infection cycle, leading to the expression of the viral structural proteins, Gag, Pol, and Env. Rev binds to a complex RNA structure, the Rev-responsive element (RRE), present in all Rev-responsive viral transcripts, relieving their nuclear sequestration. The precise mechanism by which RRE-containing transcripts are retained within the nucleus in the absence of Rev protein is not well understood. We previously demonstrated that the RRE alone plays a crucial role in the nuclear retention of RRE-containing env transcripts in stably transfected Drosophila cells. Here we extend our previous observations and demonstrate that the RRE is a principal determinant of nuclear retention for envelope transcripts in primate cells and, in particular, human CD4+ T cells.

Animals↗

A case of "eating disorder NOS": aeromedical implications of DSM-IV diagnostic criteria.

The authors describe a case of intermittent fasting and self-induced vomiting in a student aviator whose symptoms do not meet the full criteria for either anorexia or bulimia. The range of symptomatology and differential diagnosis of eating disorders is discussed. New DSM-IV diagnostic criteria for eating disorders, including Eating Disorder Not Otherwise Specified (NOS), and 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 in the early recognition of eating disorders.

Adult↗

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↗