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Biomedical subjects

R E Fisher

Publications and source records attributed to R E Fisher.

At least 19 recordsLinked to original sources

The primate appendix: a reassessment.

The presence of a vermiform appendix is often cited as a shared, derived character uniting the Hominoidea (apes and humans). However, appendix-like structures have been reported for many other primate taxa. A review of the literature reveals that the confusion arises because several different, and sometimes contradictory, criteria are enlisted to distinguish an appendix. The measures most frequently used to define this structure are gross shape and certain aspects of histology (e.g., lymphoid concentration). Unfortunately, descriptions of shape lack quantification, and histological thin-sections have not been studied for many primate taxa. In addition, although lymphoid concentration in the human appendix is known to vary considerably with age, this information is rarely reported in the primate literature. Given these complications, additional studies on the morphology and ontogeny of this region are warranted. This research will lead to a more accurate definition of the vermiform appendix. Most authors currently describe this feature as a narrow diverticulum of the cecum with thick walls and concentrated lymphoid tissue. However, the presence of thick mucosal layers and appreciable lymphoid tissue in taxa lacking appendices (e. g., Saguinus, Cercocebus) suggests that these features may be primitive primate traits. If so, wall thickness and lymphoid concentration cannot be used to define the vermiform appendix. These results suggest that a more rigorous definition of the appendix is requisite for this feature to be used in primate systematics.

Animals↗

Prognostic value of myocardial perfusion imaging in patients with high exercise tolerance.

BACKGROUND: Although high exercise tolerance is associated with an excellent prognosis, the significance of abnormal myocardial perfusion imaging (MPI) in patients with high exercise tolerance has not been established. This study retrospectively compares the utility of MPI and exercise ECG (EECG) in these patients. METHODS AND RESULTS: Of 388 consecutive patients who underwent exercise MPI and reached at least Bruce stage IV, 157 (40.5%) had abnormal results and 231 (59.5%) had normal results. Follow-up was performed at 18+/-2.7 months. Adverse events, including revascularization, myocardial infarction, and cardiac death, occurred in 40 patients. Nineteen patients had revascularization related to the MPI results or the patient's condition at the time of MPI and were not included in further analysis. Seventeen patients (12.2%) with abnormal MPI and 4 (1.7%) with normal MPI had adverse cardiac events (P<0.001). Cox proportional-hazards regression analysis showed that MPI was an excellent predictor of cardiac events (global chi2=13.2; P<0.001; relative risk=8; 95% CI=3 to 23) but EECG had no predictive power (global chi2=0.05; P=0.8; relative risk=1; 95% CI=0.4 to 3.0). The addition of Duke's treadmill score risk categories did not improve the predictive power of EECG (global chi2=0.17). The predictive power of the combination of EECG (including Duke score categories) and MPI was no better than that of MPI alone (global chi2=13.5). CONCLUSIONS: Unlike EECG, MPI is an excellent prognostic indicator for adverse cardiac events in patients with known or suspected CAD and high exercise tolerance.

Adult↗

Neural networks in ventilation-perfusion imaging.

PURPOSE: To optimize the performance of artificial neural networks in the prediction of pulmonary embolism from ventilation-perfusion (V-P) scans. MATERIALS AND METHODS: Neural networks were constructed with a set of V-P scan criteria that included sharpness and completeness of perfusion defects and involved quantification of abnormalities by using a continuous numeric scale. Several network parameters were systematically varied. Networks were trained with 150 cases and tested with 30 different cases. Findings were compared with those of pulmonary angiography. RESULTS: Networks capable of performing as well as experienced nuclear medicine physicians could be constructed with few V-P scan features. A brief training period was optimal (50-100 iterations). Further training diminished network performance. CONCLUSION: Effective neural networks can be constructed by using a limited number of unconventional V-P scan features. Several parameters can be adjusted to optimize performance.

Adolescent↗

Neural networks in ventilation-perfusion imaging. Part II. Effects of interpretive variability.

PURPOSE: To evaluate the usefulness of a neural network developed by one physician and used by another. MATERIALS AND METHODS: Intra- and interobserver variability were analyzed in image categorization of ventilation-perfusion (V-P) scans. This information was used to estimate network performance when it was used by a physician who did not train the network. RESULTS: Network training was optimized by using input parameters that demonstrated both individually high correlations with pulmonary embolism and good reproducibility in multiple interpretations. CONCLUSION: Potential variability exists in the performance of a network when it is supplied with input data by different physicians. The clinical usefulness of a network depends heavily on the similarity of interpretive styles between the network trainer and the user.

Humans↗

Epidemiology and etiology of leukemia.

New clinical and epidemiologic studies provide information about the possible causes of human leukemia. Evidence for a viral etiology continues to appear, and the relationship between myelodysplastic syndrome and the leukemias is now linked through molecular genetic studies. Molecular mechanisms of leukemogenesis are being understood through evaluation of preleukemic conditions and predisposing medical illnesses. Epipodophyllotoxins and, to a lesser extent, cisplatin are being linked causally to secondary leukemia. Potential environmental causes of leukemia are being intensively investigated with both positive and negative results. The literature on the epidemiology of leukemia is growing rapidly, and important leads toward a more complete understanding of its etiology are emerging.

Alkylating Agents↗

The evolution of defective and autonomous parvoviruses.

Because of the small size and genetic simplicity of small DNA viruses, parvoviruses would appear to be excellent models for studying viral evolution and adaptation. In an earlier publication we hypothesized the evolution of sequences of cellular "junk" DNA into protective interfering transposons. These transposons would interfere with invading pathogenic viruses by competing with the pathogen DNA for replicative enzymes. We speculated that a small, defective parvovirus, the adeno-associated virus (AAV), which usually requires the presence of a pathogenic helper virus to replicate, may have evolved from such a piece of cellular "junk" DNA. Our theory predicted that AAVs, as a consequence of their defective nature, developed under pressures favoring maintenance of their transposon like qualities. In contrast, disease-causing, autonomous, non-defective parvoviruses such as the B19 agent of humans and the canine parvovirus, even though their origins may have been in cellular DNA, would appear to have developed under totally different evolutionary pressures. In this paper we will present evidence for a common ancestry for the defective and autonomous parvoviruses and discuss the divergent paths this evolution may have taken in establishing the two genera.

Base Sequence↗

Properties and distribution of single voltage-gated calcium channels in adult hippocampal neurons.

1. The properties of single voltage-gated calcium channels were investigated in acutely exposed CA3 and CA1 pyramidal neurons and granule cells of area dentata in the adult guinea pig hippocampal formation. 2. Guinea pig hippocampal slices were prepared in a conventional manner, then treated with proteolytic enzymes and gently shaken to expose the somata of the three cell types studied. Standard patch-clamp techniques were used to record current flow through calcium channels in cell-attached membrane patches with isotonic barium as the charge carrier. 3. Single-channel current amplitudes were measured at different membrane potentials. Single-channel current-voltage plots were constructed and single-channel slope conductances were found to fall into three classes. These were (approximately) 8, 14, and 25 pS, and were observed in all three cell types. 4. The three groups of channels differed from each other in voltage dependence of activation: from a holding potential of -80, the small-conductance channel began to activate at about -40 to -30 mV, the medium-conductance channel at about -20 mV, and the large-conductance channel at approximately 0 mV. 5. Ensemble averages of single-channel currents during voltage steps revealed differences in voltage-dependent inactivation. The small-conductance channel inactivated completely within approximately 50 ms during steps from -80 to -10 mV or more positive. Steps to less positive potentials resulted in less inactivation. The medium-conductance channel displayed variable inactivation during steps from -80 to 0 mV. Inactivation of this channel during a 160-ms step ranged from virtually zero to approximately 100%. The large-conductance channel displayed no significant inactivation during steps as long as 400 ms. 6. The large-conductance channel was strikingly affected by the dihydropyridine agonist Bay K8644 (0.5-2.0 microM), resulting in a high probability of channel opening, prolonged openings, and an apparent increase in the number of channels available for activation. The medium and small-conductance channels were not noticeably affected by the drug. 7. The large-conductance channel could be induced to open at very negative membrane potentials by holding the patch for several seconds at 20 or 30 mV and stepping to -30 or -40 mV. This process was enhanced by Bay K8644, resulting in prolonged openings at potentials as negative as -100 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

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

Evolution of a defective virus from a cellular defense mechanism.

Adeno-associated virus is a defective DNA virus, requiring the presence of a helper virus in order to replicate. In this paper we consider its origin in light of several observations, most notably the following: its own replication inhibits that of the helper virus; its DNA structure resembles that of transposable (moveable) elements; and extrachromosomal circles of DNA, about the size of adeno-associated virus DNA, have been found recently in eukaryotic cells. We have arrived at a hypothesis consisting of two main ideas: (1) that cells may use transposable DNA as a mechanism of defense against viral attack, and (2) that adeno-associated virus may have evolved directly from this cellular defense mechanism.

Biological Evolution↗

Death penalty.

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Capital Punishment↗

Keratoacanthoma.

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Carcinoma, Squamous Cell↗