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Biomedical subjects

Mark A King

Publications and source records attributed to Mark A King.

13 recordsLinked to original sources

The cytoskeletal organizing protein Cdc42-interacting protein 4 associates with phosphorylase kinase in skeletal muscle.

Phosphorylase kinase is a key enzyme in regulating glycogenolytic flux in skeletal muscle in response to changing energy demands. In the present study, we sought to identify interacting proteins of phosphorylase kinase by yeast two-hybrid screening. Screening a rabbit skeletal muscle cDNA library with the exposed C-terminus of the alpha subunit (residues 1060-1237), we identified eight independent, yet overlapping, constructs of cdc42-interacting protein 4 (CIP4). Immunocytochemistry indicated that CIP4 colocalized with phosphorylase kinase in vivo, and the cognate binding domain on CIP4 was determined to lie between residues 398 and 545. While this region of CIP4 does contain a known src homology 3 domain, transient transfections and coimmunoprecipitation experiments showed that this domain is not responsible for the dimeric interaction. Based upon sequence analysis the association is inferred to be mediated by two proline-rich sequences in CIP4, residues 436-439 and 441-444, that bind to a cognate WW domain found between residues 1107 and 1129 of PhKalpha.

Animals↗

Correlation of magnetic resonance imaging with histopathology in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C).

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an asymptomatic cardiac disease characterized by fatty infiltration of the right ventricular myocardium and often results in sudden cardiac death. ARVD/C diagnosis includes the assessment of fatty infiltration, which can be achieved noninvasively with cardiovascular magnetic resonance (CMR). The standard CMR protocol places the signal-generating coil directly on the anterior chest wall and produces a nonspecific high intensity signal that obscures the high signal from fatty infiltration. The aim of this study was to determine whether increasing the coil-to-chest distance would improve identification of fatty infiltration. Thoraces from seven embalmed cadavers were imaged on a conventional 1.5 Tesla CMR scanner using the control protocol and an experimental protocol, with a 6 cm coil-to-chest distance. A representative axial MR image and corresponding gross section of the heart were analyzed in each case. Fatty infiltration was graded in a blinded fashion on the MR images with independent histopathologic assessment. In five of the seven cases, the experimental protocol provided a correlation between CMR and histopathology that was as good as or better than the control protocol. The experimental protocol was also better in preventing false positive diagnosis in cases of minimal infiltration. Thus, the experimental protocol showed a stronger correlation with histopathology than did the control protocol. Increasing the distance between the anterior surface coil and chest wall may improve classification of presence or absence of fatty infiltration in the right ventricular myocardium, potentially improving the noninvasive detection of ARVD/C with CMR.

Adipose Tissue↗

Modelling the maximum voluntary joint torque/angular velocity relationship in human movement.

The force exerted by a muscle is a function of the activation level and the maximum (tetanic) muscle force. In "maximum" voluntary knee extensions muscle activation is lower for eccentric muscle velocities than for concentric velocities. The aim of this study was to model this "differential activation" in order to calculate the maximum voluntary knee extensor torque as a function of knee angular velocity. Torque data were collected on two subjects during maximal eccentric-concentric knee extensions using an isovelocity dynamometer with crank angular velocities ranging from 50 to 450 degrees s(-1). The theoretical tetanic torque/angular velocity relationship was modelled using a four parameter function comprising two rectangular hyperbolas while the activation/angular velocity relationship was modelled using a three parameter function that rose from submaximal activation for eccentric velocities to full activation for high concentric velocities. The product of these two functions gave a seven parameter function which was fitted to the joint torque/angular velocity data, giving unbiased root mean square differences of 1.9% and 3.3% of the maximum torques achieved. Differential activation accounts for the non-hyperbolic behaviour of the torque/angular velocity data for low concentric velocities. The maximum voluntary knee extensor torque that can be exerted may be modelled accurately as the product of functions defining the maximum torque and the maximum voluntary activation level. Failure to include differential activation considerations when modelling maximal movements will lead to errors in the estimation of joint torque in the eccentric phase and low velocity concentric phase.

Humans↗

Parameter determination for a computer simulation model of a diver and a springboard.

This study used kinematic data on springboard diving performances to estimate viscoelastic parameters of a planar model of a springboard and diver with wobbling masses in the trunk, thigh, and calf segments and spring dampers acting at the heel, ball, and toe of the foot segment. A subject-specific angle-driven eight-segment model was used with an optimization algorithm to determine viscoelastic parameter values by matching simulations to four diving performances. Using the parameters determined from the matching of a single dive in a simulation of another dive resulted in up to 31% difference between simulation and performance, indicating the danger of using too small a set of kinematic data. However, using four dives in a combined matching process to obtain a common set of parameters resulted in a mean difference of 8.6%. Because these four dives included very different rotational requirements, it is anticipated that the combined parameter set can be used with other dives from these two groups.

Acceleration↗

Determination of subject-specific model parameters for visco-elastic elements.

The determination of subject-specific model parameter values is necessary in order for a computer simulation model of human motion to be evaluated quantitatively. This study used an optimisation procedure along with a kinematically driven simulation model of the contact phase in running jumps to determine the elastic parameters of segmental wobbling masses and the foot-ground interface. Kinetic and kinematic data were obtained on running jumps for height and distance performed by an elite male high jumper. Stiffness and damping coefficients of the visco-elastic elements in the model were varied until the difference between simulation and performance was minimised. Percentage differences of 6% and 9% between the simulated and recorded performances were obtained in the jumps for height and distance, respectively. When the parameters obtained from the jump for height were used in a simulation of the jump for distance (and vice versa), there was poor agreement with the recorded jump. On the other hand, a common set of visco-elastic parameters were obtained using the data from both recorded jumps resulting in a mean difference of only 8% (made up of 7% and 10%) between simulation and performance that was almost as good as the individual matches. Simulations were not overly sensitive to perturbations of the common set of visco-elastic parameters. It is concluded that subject-specific elastic parameters should be calculated from more than a single jump in order to provide a robust set of values that can be used in different simulations.

Biomechanical Phenomena↗

Factors influencing performance in the Hecht vault and implications for modelling.

This paper investigated the factors that influence Hecht vault performance and assessed the level of model complexity required to give an adequate representation of vaulting. A five-segment planar simulation model with a visco-elastic shoulder joint and a torque generator at the shoulder joint was used to simulate the contact phase in vaulting. The model was customized to an elite gymnast by determining subject-specific segmental inertia and joint torque parameters. The simulation model was matched to a performance of the Hecht vault by varying the visco-elastic characteristics of the shoulders and the arm-horse interface and the activation time history of the shoulder torque generator until the best match was found. Perturbing the matching simulation demonstrated that appropriate initial kinematics are necessary for a successful performance. Fixing the hip and knee angles at their initial values had a small effect with 3 degrees less rotation. Applying shoulder torque during the contact phase also had a small effect with only a 7 degrees range in landing angles. Excluding the hand segment from the model was found to have a moderate effect with 15 degrees less rotation and the time of contact reduced by 38%. Removing shoulder elasticity resulted in 50 degrees less rotation. The use of a five-segment simulation model confirmed that the use of shoulder torque plays a minor role in vaulting performance and that having appropriate initial kinematics at touchdown is essential. However, factors such as shoulder elasticity and the hands which have previously been ignored also have a substantial influence on performance.

Biomechanical Phenomena↗

Endobronchial histoplasmosis: a masquerade of primary endobronchial neoplasia--a clinical study of four cases.

BACKGROUND: Histoplasma capsulatum is a dimorphic fungus with both hyphal and microconidial elements and is endemic in certain areas of the central United States. Most clinically recognized syndromes are self-limited, presenting in more than 80% of cases as an influenza-like acute pulmonary illness. We encountered four patients with an endobronchial presentation of histoplasmosis masquerading as a bronchogenic malignancy. METHODS: The patient files from one of the authors (PR) uncovered four patients diagnosed with, and treated for, endobronchial histoplasmosis; all cases were referred for a presumptive diagnosis of endobronchial neoplasia. RESULTS: The case study group comprised three women, ages 52, 68, and 81 years, respectively, and one man age 29 years, all presenting with recurrent hemoptysis. An obstructing adherent lesion was apparent on bronchoscopy in three, involving the right upper lobe bronchus in two, and right mainstem bronchus in one. In one patient, blood was observed in the bronchus intermedius; there was no gross lesion. Recurrent hemoptysis necessitated a right upper sleeve lobectomy in one, a right upper lobe lobectomy and right lower wedge resection in one, a right middle lobectomy in one, and wedge resection of the right upper lobe in one. CONCLUSIONS: Endobronchial histoplasmosis may mimic primary bronchogenic carcinoma, presenting as a fixed obstructing endobronchial lesion associated with hemoptysis; the latter potentially necessitating surgical intervention. Endobronchial histoplasmosis should be considered in the differential diagnosis of obstructing endobronchial lesions associated with hemoptysis, especially when prior and(or) concurrent biopsies fail to disclose malignancy.

Adult↗

Atypical thymoma: a report of seven patients.

BACKGROUND: Most thymic neoplasms fall under the designation of thymoma, consisting of well-differentiated epithelial cells, resembling normal thymus. At the opposite spectrum are thymic carcinomas; the cell of origin while similar is malignant. Recently a third category of thymic neoplasms, atypical thymomas, has been recognized representing thymic neoplasms manifesting atypia although without overt cytomorphologic criteria of malignancy. METHODS: Seven patients with a diagnosis of atypical thymoma were encountered over a 6-year period from the patient files of the cardiothoracic division of The Ohio State Medical Center. RESULTS: In all patients there was gross or light microscopic invasive disease with involvement of the capsule, phrenic nerve, diaphragm, chest wall, and lung. Surgical extirpation/de-bulking along with radiation therapy in six and chemotherapy in one led to complete disease regression. Intrathoracic recurrences developed in 4 involving lung, pleura, chest wall and diaphragm. All patients are well. CONCLUSIONS: Atypical thymomas are locally aggressive tumors with a high incidence of intrathoracic recurrence; extrathoracic spread is not seen. Our study corroborates other reports that death attributable to atypical thymoma is uncommon.

Adult↗

EEG in adult-onset idiopathic generalized epilepsy.

PURPOSE: It remains controversial whether adult-onset idiopathic generalized epilepsy (IGE) is a distinct syndrome or a continuum among IGE syndromes. EEG is the only known biologic marker of IGE and helps differentiate many of its classic subsyndromes. In this study, we looked for the differences in the EEG findings of IGE of classic adolescent onset versus adult onset that may suggest syndromic heterogeneity. METHODS: Seventy-six patients (47 adolescent-onset IGE, 29 adult-onset IGE) with a clinical and EEG diagnosis of IGE were included. We defined IGE with age at onset of 11-20 years as adolescent-onset IGE and age at onset of 20 years or after as adult-onset IGE. Patients with first-decade onset of seizures, delayed EEGs, and no EEG available for review were excluded. The first EEG was performed within 24 h of the seizure, and if negative, a sleep-deprived EEG was done. All EEGs were reviewed in detail with respect to the background activity and the generalized spike-wave (GSW) characteristic. RESULTS: EEGs (87; 56 adolescent-onset IGE, 31 adult-onset IGE) were systematically reviewed. Background was normal in all patients. The morphology, amplitude, duration, frequency, occurrence, or activation of the GSW pattern did not differ between these two groups. CONCLUSIONS: No differences of EEG features were found between the classic adolescent-onset and the adult-onset IGE. This supports the hypothesis that they share common biologic determinants and exist along a life-long age spectrum of classic IGE.

Adolescent↗

Mature teratoma within the posterior mediastinum.

Mature teratomas in the chest are typically located within the anterior mediastinum. The authors report a case of a mature teratoma in a young adult male with characteristic imaging features except for its location: the posterior mediastinum. On review of the literature, 3% to 8% are reported as confined to the posterior mediastinum and 13% have extension into other mediastinal compartments.

Adult↗

Seizure-associated hippocampal volume loss: a longitudinal magnetic resonance study of temporal lobe epilepsy.

This longitudinal quantitative magnetic resonance imaging study of 24 patients with mild temporal lobe epilepsy shows an ipsilateral hippocampal volume decrease of 9% (range, -30 to +0.5%; p = 0.002, paired t test) over a period of 3.5 +/- 0.7 years. The hippocampal volume loss was correlated to the number of generalized seizures between the scans (p = 0.0007, r = 0.6), suggesting seizure-associated hippocampal damage.

Adolescent↗

The eosinophilic pneumonias.

Acute and chronic eosinophilic pneumonia can be distinguished by their clinical, laboratory, and radiographic features. Patients with both acute and chronic eosinophilic pneumonia present with cough, dyspnea, and fever. Patients with chronic eosinophilic pneumonia present subacutely over weeks to months but patients with acute eosinophilic pneumonia present within 5 days of symptom onset. Chest radiographs in chronic eosinophilic pneumonia show peripheral alveolar infiltrates. In contrast, radiographs in acute eosinophilic pneumonia show mixed interstitial and alveolar infiltrates, Kerley B lines, and pleural effusions. Both disorders are characterized by high percentages of bronchoalveolar lavage eosinophils, but high numbers of blood eosinophils accompanies only chronic eosinophilic pneumonia. The diagnosis of both disorders can usually be made based on clinical and radiographic findings; however, lung biopsy is occasionally necessary to distinguish the eosinophilic pneumonias from other eosinophilic lung diseases. In both conditions, patients will respond rapidly and completely to corticosteroids but patients with chronic eosinophilic pneumonia usually relapse if less than 6 months of treatment is given, whereas patients with acute eosinophilic pneumonia do not relapse after a brief course of treatment.

Journal Article↗

Missed cervical spine fracture-dislocations: the importance of clinical and radiographic assessment.

OBJECTIVE: To review the case of a patient who suffered a cervical spine fracture-dislocation missed at a hospital emergency department. CLINICAL FEATURES: A 77-year-old man involved in a motor vehicle accident was transported to a local emergency hospital where cervical spine x-ray films taken were reported as demonstrating no evidence of acute injury. The patient visited a chiropractic clinic 6 days later, where x-ray films were again obtained, finding that the patient sustained fractures of C5 and C6, as well as a bilateral facet dislocation at C5/C6. Computed tomography confirmed the fractures, and magnetic resonance imaging findings demonstrated cervical spinal cord compression and posterior spinal cord displacement. INTERVENTION AND OUTCOME: The patient was referred for preoperative medical evaluation. He underwent C5-6 closed reduction and anterior/posterior fusion surgery and was released without complication. Patient follow-up indicated full recovery with minimal neurologic symptoms. CONCLUSION: Cervical spine fracture-dislocations are often missed during standard radiographic examinations in emergency department settings. Chiropractors are encouraged to perform a comprehensive evaluation of patients presenting with cervical trauma even if they have had prior x-ray films reported as normal. Standard x-ray films taken at emergency department facilities are not entirely reliable for detecting or revealing cervical spine fracture-dislocations. This case stresses the importance of careful clinical assessment and imaging procedures on patients who have encountered cervical spine trauma.

Aged↗