We propose a novel formalism, called Frame Logic (abbr., F-logic), that accounts in a clean and declarative fashion for most of the structural aspects of object-oriented and frame-based languages. These features include object identity, complex objects, inheritance, polymorphic types, query methods, encapsulation, and others. In a sense, F-logic stands in the same relationship to the objectoriented paradigm as classical predicate calculus stands to relational programming. F-logic has a model-theoretic semantics and a sound and complete resolution-based proof theory. A small number of fundamental concepts that come from object-oriented programming have direct representation in F-logic other, secondary aspects of this paradigm are easily modeled as well. The paper also discusses semantic issues pertaining to programming with a deductive object-oriented language based on a subset of F-logic.

HCN cation channel mRNA expression was determined in the rabbit heart and neonatal and adult rat ventricle using RNase protection assays. In the rabbit SA node, the dominant HCN transcript is HCN4, representing >81% of the total HCN message. HCN1 is also expressed, representing >18% of the total HCN mRNA. Rabbit Purkinje fibers contained almost equal amounts of HCN1 and HCN4 transcripts with low levels of HCN2, whereas rabbit ventricle contained predominantly HCN2. The SA node contained 25 times the total HCN message of Purkinje fibers and 140 times the total HCN message of ventricle. No reports of hyperpolarization-activated current (If) exist in rabbit Purkinje fibers, and we could not record If in rabbit ventricular myocytes. To investigate the possible role of isoform switching in determining the voltage dependence of If, we determined the prevalence of HCN isoforms in neonatal and adult rat ventricle. We had previously determined the threshold for activation of If to be approximately -70 mV in neonatal rat ventricle and -113 mV in adult rat ventricle. In both neonatal and adult rat ventricle, only HCN2 and HCN4 transcripts are present. The ratio of HCN2 to HCN4 is approximately 5:1 in the neonate and 13:1 in the adult. Taken together, these results suggest that different cardiac regions express different isoforms of the HCN family. The HCN1 and HCN4 isoforms are most closely associated with a depolarized threshold for If activation, whereas the HCN2 isoform is associated with a more negative activation curve.

To determine the incidence of nodal involvement and assess the role of elective lymph node (LN) exploration and/or dissection in staging of tumors and treatment of patients with papillary thyroid cancer.Design: Retrospective medical chart review.Setting: Academic tertiary care medical center.Patients: One hundred patients diagnosed with papillary thyroid cancer by fine-needle aspiration or intraoperative frozen section who underwent total thyroidectomy with central compartment cervical LN exploration.Main Outcome Measure: Incidence of positive LNs in patients 45 years or older (group A) vs those younger than 45 years (group B).Results: Sixteen (39%) of 41 patients in group A had positive LN status following LN exploration and/or dissection. Seventeen (29%) of 59 patients in group B were found to have positive LNs. According to the American Joint Committee on Cancer staging system, the tumors of 11 patients (28%) in group A would be restaged from stage I/II to stage III after establishment of the positive pathologic nodal status.Conclusions: Lymph node metastasis was present in the central compartment in 39% of patients in group A. Presence of LN metastasis in older patients has been reported to increase the risk of recurrence of papillary thyroid carcinoma. Furthermore, recurrence and reoperation in the central compartment is associated with a higher risk of vocal cord paralysis. In patients in group A diagnosed with papillary thyroid carcinoma, routine central compartment LN exploration and/or dissection at the time of thyroidectomy is advocated, which allows more accurate staging of tumors and appropriate treatment. Elective excision of central compartment LNs in this older age group may improve locoregional control and possibly reduce morbidity in the long run.

TNM, EORTC, AGES, AMES, and MACIS, all provided useful prognostic information about the survival in our 86 patients with follicular thyroid cancers. The MACIS classification, however, was the most accurate predictor using PVE as a method of evaluation. Future scoring systems considering additional prognostic factors, may obtain a higher PVE.

Approaching the nerve along its distal portion is safe and effective. The surgical topographical anatomy in this region is described in detail. Some of the potential advantages of identifying the nerve more distally include less chance of disrupting the blood supply to the inferior parathyroid gland, dissection along a shorter portion of the nerve, and less variability of the nerve.

We studied pacemaker current (i(f)), the inward current activated by hyperpolarization in rabbit sinoatrial (SA) node myocytes, with the permeabilized-patch-clamp technique. The tyrosine kinase inhibitors genistein (50 microM) or herbimycin A (35 microM) reduced the amplitude of i(f) in response to step hyperpolarizations in the diastolic range of potentials. A two-step voltage-clamp protocol revealed that the reduction in i(f) is due to a decrease in maximal i(f) conductance. The observed effects are due to tyrosine kinase inhibition since an inactive analog of genistein did not reduce i(f). To further examine the mechanism of action, we added 2 mM chlorophenylthio cAMP (CPTcAMP, a membrane-permeant cAMP analog) to the bathing Tyrode, which increased i(f). Genistein still reduced i(f) in the presence of CPTcAMP. This suggests that the pathway mediating the actions of tyrosine kinase inhibition on i(f) is independent of cAMP- or protein-kinase-A-mediated phosphorylation.

Our previous results have demonstrated that tyrosine kinase inhibition reduces i(f) in rabbit SA node myocytes, suggesting that tyrosine kinases regulate i(f). One receptor tyrosine kinase the EGF receptor kinase is known to increase heart rate. To determine if this action is mediated through changes in i(f), we examined the effect of epidermal growth factor (EGF) on i(f) with the permeabilized patch-clamp technique. 0.1 microM EGF increased i(f) amplitude in response to single-step hyperpolarizations in the diastolic range of potentials. This increase was 20+/-3%, n=11 at -75 mV. This effect is caused by activating a tyrosine kinase because 50 microM genistein, a tyrosine kinase inhibitor, eliminated this EGF action. A two-step pulse protocol showed that maximal i(f) conductance was increased by EGF. We further examined this conductance change by constructing the activation curve. The maximal i(f) conductance was increased by 23% with no change in midpoint, V(1/2), control=-74+/-2 mV, V(1/2) EGF=-74+/-1 mV. Thus EGF acts via a tyrosine kinase to increase maximal i(f) conductance with no change in the voltage dependence of activation. These results suggest that EGF effects on i(f) contribute to the positive chronotropic effect of EGF on SA node.

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