A computational model for glycogenolysis in skeletal muscle

A dynamic model of the glycogenolytic pathway to lactate in skeletal muscle was constructed with mammalian kinetic parameters obtained from the literature. Energetic buffers relevant to muscle were included. The model design features stoichiometric constraints, mass balance, and fully reversible thermodynamics as defined by the Haldane relation. We employed a novel method of validating the thermodynamics of the model by allowing the closed system to come to equilibrium; the combined mass action ratio of the pathway equaled the product of the individual enzymes' equilibrium constants. Adding features physiologically relevant to muscle—a fixed glycogen concentration, efflux of lactate, and coupling to an ATPase—allowed for a steady-state flux far from equilibrium. The main result of our analysis is that coupling of the glycogenolytic network to the ATPase transformed the entire complex into an ATPase driven system. This steady-state system was most sensitive to the external ATPase activity and not to internal pathway mechanisms. The control distribution among the internal pathway enzymes—although small compared to control by ATPase—depended on the flux level and fraction of glycogen phosphorylase a. This model of muscle glycogenolysis thus has unique features compared to models developed for other cell types. © 2002 Biomedical Engineering Society. PAC2002: 8719Ff, 8239Fk, 8718Bb, 8714Ee     

Pathogenic Yersinia DNA is detected in bowel and mesenteric lymph nodes from patients with Crohn's disease

Previously, we detected pathogenic (invasive) DNA in the appendices of two patients who later developed Crohn's disease (CD). This subsequent investigation is the first to evaluate a series of specimens from CD patients for the presence of pathogenic DNA. A total of 54 intestinal resection specimens from 52 patients with confirmed CD were evaluated. Lesional tissue was tested by polymerase chain reaction analysis for the presence of genes occurring only in pathogenic Primer pairs are specific for each species, with no known cross reactions with other bacteria. Forty normal bowel specimens, 30 cases of acute appendicitis, and 50 cases of various active colitides served as disease controls. Medical records were reviewed following polymerase chain reaction and histologic evaluation. A total of 17 of 54 resections (31%) contained DNA by polymerase chain reaction. Mesenteric lymph nodes were also positive in eight of these cases. All controls were negative. -positive patients had carried the diagnosis of CD for a median of 10 years before resection (range 1 month to 40 years). We report the first documentation of DNA in a series of CD cases. Further studies are needed, including serial study, over time, of -positive CD patients, as well as prospective studies of newly diagnosed CD patients for evidence of infection. Like previous studies associating infectious organisms with CD, much work remains to elucidate whether the presence of DNA is an epiphenomenon or actually a factor in the pathogenesis of CD.     

Neuropsychological effects of third ventricle tumor surgery

OBJECTIVE: This study assessed the neuropsychological outcome of patients after surgical treatment for third ventricle brain tumors. Neuropsychological consequences of surgical intervention can have a major impact on patients' quality of life and therefore have important implications for treatment planning. METHODS: A retrospective analysis of 33 patients' neuropsychological data was performed. All patients received a comprehensive neuropsychological evaluation after treatment for a primary brain tumor in the third ventricular region. Twenty-six patients underwent surgery, 14 via the transcallosal approach and 12 via a subfrontal, left transcortical, right pterional, or infratentorial supracerebellar approach. Seven patients were not treated by surgical intervention. RESULTS: There was a significantly elevated frequency of cognitive impairment relative to normative values in memory, executive functioning, and fine manual speed and dexterity. There were no differences in mean neuropsychological scores between patients who underwent surgery and those who did not. There were no differences in mean performance on the basis of surgical approach, tumor infiltration, or history of cranial irradiation. Repeated measures data available for two patients revealed memory impairment before and after surgery, and one patient experienced major improvement after surgery on a measure of mental flexibility and problem solving. CONCLUSION: Patients with third ventricle tumors are at risk for developing impairments in memory, executive function, and fine manual speed and dexterity, which are domains associated with frontal subcortical functions. In the current study, different types of treatment were not associated with differential cognitive sequelae, and surgical intervention did not account for cognitive deficits.     

Mammographic-pathologic correlation of apocrine metaplasia diagnosed using vacuum-assisted stereotactic core-needle biopsy: our 4-year experience

OBJECTIVE: To determine whether focal apocrine metaplasia of the breast has distinctive mammographic characteristics, we evaluated apocrine metaplasia diagnosed by vacuum-assisted stereotactic core-needle biopsy and correlated mammographic imaging and histopathologic findings. MATERIALS AND METHODS: We retrospectively reviewed our institutional database for records of all vacuum-assisted stereotactic core-needle biopsies performed during a 4-year period. Five hundred thirty-eight lesions were biopsied, of which 302 (56%) were benign. Apocrine metaplasia was diagnosed in 37 lesions. In 11 of these 37 lesions, apocrine metaplasia made up more than 50% of the lesion sampled. RESULTS: On mammography, eight cases (73%) appeared as new or increasing calcifications, and three cases (27%) appeared as new or enlarging equal-density masses (0.6-1.2 cm). Calcifications were heterogeneous in five lesions (63%), amorphous in two (25%), and punctate in one (12%); one heterogeneous cluster of calcifications (12%) also contained milk of calcium. The pattern of calcification distribution was clustered in five lesions (63%), multiple clusters in two (25%), and linear in one (12%). Two masses (67%) were lobular, and one (33%) was round. Two borders (67%) were microlobulated, and one (33%) was circumscribed. CONCLUSION: Apocrine metaplasia is a benign condition commonly associated with other fibrocystic changes. Lesions composed of more than 50% focal apocrine metaplasia are relatively uncommon. A new or enlarging lobular, microlobulated mass or heterogeneous calcification cluster may represent apocrine metaplasia. Because no distinguishing mammographic features are present to require follow-up by imaging, needle biopsy is required for definitive diagnosis.     

Ventricular constraint in severe heart failure halts decline in cardiovascular function associated with experimental dilated cardiomyopathy

BACKGROUND: We have shown that passive ventricular constraint during moderate heart failure can halt progressive deterioration in cardiac function in an experimental model of ovine pacing induced heart failure (HF). We report on ventricular constraint in severe heart failure. METHODS: Eighteen adult merino sheep were used. Severe heart failure was induced in two stages, ie, high rate ventricular pacing for 21 days to produce moderate HF and then for 42 days to induce severe HF. A custom-made polyester mesh cardiac support device ([CSD] Acorn Cardiovascular, St Paul, MN) was implanted snugly around both ventricles through a lower partial sternotomy in 9 sheep (group 1). Rapid ventricular pacing was continued for a further 28 days in all animals to induce advanced HF. Cardiovascular functional indicators were determined using echocardiography and a submaximal treadmill exercise protocol at base line, moderate, severe, and advanced stages. The 9 sheep in group 2 were used as controls. RESULTS: Cardiovascular function was significantly depressed in all animals in advanced heart failure compared with base line, with left ventricular ejection fraction (LVEF) falling from 50% to 25% (p < 0.05) and LV +dp/dt((max)) declining from 1,777 to 1,243 (p < 0.05). However after CSD implantation cardiovascular function during exercise improved significantly despite ongoing rapid pacing, with LVEF increasing to 30% and LV +dp/dt to 1,499 (p < 0.05) in group 1. There were no significant changes in left ventricular long axis area (157 to 151 cm(2)) and short axis (6.8 to 6.1 cm) dimensions at the termination of pacing compared with those at time of CSD implant. Mitral regurgitation improved slightly from 2.5 to 2.19 after containment (p < 0.05) in group 1 but increased to 2.83 in group 2. CONCLUSIONS: Ventricular constraint in advanced heart failure with a custom-made polyester mesh device halted the decline in cardiac function seen in untreated animals with this pacing-induced animal model of heart failure. These results indicate potential clinical implications for ventricular containment in the treatment of end-stage heart failure.