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Biomedical subjects

M Paine

Publications and source records attributed to M Paine.

16 recordsLinked to original sources
PubMed2002

Perceiving an entire object and grasping only half of it.

A single case study is presented of an unusual dissociation between the sensory perception of an object and the grasping action towards the same object. The patient IW was found at age 74 to have spent all his life without the left parietal lobe, as a result of a congenital peri-natal insult. IW does not show any signs of sensory dysfunction, but he has a persistent motor bias that arises during movement towards objects. When IW was required to reach and grasp stationary and rotating objects, he consistently grasped the objects to the left side. Thus, it appears that information that is available at a sensory level can nevertheless be unavailable at a motor level. Our findings not only help to clarify the functions of the parietal lobe, but also show that lesions in this area are linked specifically to a process of response performance, which is fundamental for our understanding of visuomotor control.

Aged↗
PubMed2001

Steroid management in giant cell arteritis.

AIM: Ocular involvement in giant cell arteritis (GCA) is an ophthalmic emergency which, if untreated, can progress to permanent blindness. There is little evidence in the literature to support current protocols for the acute treatment of GCA with steroids. The authors sought to review the effects of intravenous and oral steroids in GCA. METHODS: This retrospective study reviewed the records of 100 consecutive patients with biopsy proved giant cell arteritis. 73 patients with visual loss who were treated at the Royal Victorian Eye and Ear Hospital (RVEEH) and St Vincent's Hospital were included in the final series. The authors studied the management of the patients in the first week after presentation, analysing types of treatment, dose, effect on visual acuity, and complications. RESULTS: All the patients except one had visual loss due to anterior ischaemic optic neuropathy (AION). 17 patients (23%) had bilateral eye involvement. Visual acuity improved in 21 of 73 patients (29%) by a mean of two Snellen chart lines after commencement of steroids. There was an increased likelihood of improved vision in the group who had intravenous steroids (40%) compared with those who received oral steroids (13%). In all except four patients (95%) vision remained stable at 1 month review. CONCLUSIONS: Prompt treatment of GCA with steroids leads to improvement of visual acuity in a significant number of cases. Intravenous steroids may offer a greater prospect of improvement compared with oral steroids. A prospective trial comparing intravenous with oral steroids is needed to validate these findings and would not expose elderly patients to unacceptable risks.

Administration, Oral↗
PubMed2000

Trp-676 facilitates nicotinamide coenzyme exchange in the reductive half-reaction of human cytochrome P450 reductase: properties of the soluble W676H and W676A mutant reductases.

The kinetics of flavin reduction in two mutant forms of human cytochrome P450 reductase have been studied by stopped-flow spectroscopy with absorption and fluorescence detection. The mutant enzymes were altered at the position of Trp-676, which, by analogy with the structure of rat CPR, is close to the isoalloxazine ring of the enzyme-bound FAD. We show that mutant CPRs in which Trp-676 has been changed to histidine (W676H) and alanine (W676A) can be reduced by NADPH only to the two-electron level in single mixing stopped-flow experiments. The concentration dependence of the rate of hydride transfer indicates that the second, noncatalytic NADPH-binding site present in wild-type CPR is retained in the mutant enzymes. Detailed studies of W676H CPR indicate that further reduction of the enzyme beyond the two electron level is prevented due to the slow release of NADP(+) from the active site following the first hydride transfer from NADPH, owing to the stability of a reduced enzyme-NADP(+) charge-transfer complex. Reduction to the four-electron level is achieved in a sequential mixing stopped-flow experiment. In this procedure, W676H CPR is reacted first with a stoichiometric amount of NADPH, and then, following a delay of 100 ms, with excess NADPH. The data indicate that occupancy of the noncatalytic coenzyme site also hinders NADP(+) release from reduced enzyme. Fluorescence stopped-flow studies of the W676H and wild-type CPR enzymes reveal that the complex signals associated with reduction of wild-type CPR by NADPH are attributable to changes in the environment of residue W676. From these studies, a model is proposed for nicotinamide binding in wild-type CPR. In this model W676 serves as a trigger to release NADP(+) from the active site following hydride transfer. In the W676H enzyme, the slow release of NADP(+) is a consequence of the combined effects of (i) removing W676 by mutagenesis (thus removing the trigger for displacement) and (ii) the binding of NADPH in the noncatalytic site, thus trapping NADP(+) in the catalytic site.

Alanine↗
PubMed2000

Susac syndrome: microangiopathy of the retina, cochlea and brain.

BACKGROUND: Susac syndrome is characterized by the triad of branch retinal arterial occlusions, encephalopathy and cochlear microangiopathy. The underlying process is believed to be a small vessel vasculitis causing microinfarcts in the retina, brain and cochlea. METHODS: Analysis of two male and two female cases of Susac syndrome recognized in Australia. RESULTS: In this series the epidemiology, mode of presentation, ophthalmologic features, neurologic and cochleo-vestibular features, radiologic characteristics, cerebrospinal fluid findings, therapeutic interventions, clinical course and outcome of Susac syndrome is examined. Key ophthalmologic differential diagnoses include systemic lupus erythematosis (SLE), Behçet's syndrome and other vasculitides such as sarcoidosis, tuberculosis, syphilis and lymphoma. Neuro-otologic features are most frequently misdiagnosed as multiple sclerosis. CONCLUSION: Susac syndrome, first described in 1979, is becoming an increasingly recognized condition. Early recognition of the syndrome is important because treatment with systemic immunosuppression may minimize permanent cognitive, audiologic and visual sequelae.

Adult↗
PubMed1999

Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution.

The crystal structure of the FMN-binding domain of human NADPH-cytochrome P450 reductase (P450R-FMN), a key component in the cytochrome P450 monooxygenase system, has been determined to 1.93 A resolution and shown to be very similar both to the global fold in solution (Barsukov I et al., 1997, J Biomol NMR 10:63-75) and to the corresponding domain in the 2.6 A crystal structure of intact rat P450R (Wang M et al., 1997, Proc Nat Acad Sci USA 94:8411-8416). The crystal structure of P450R-FMN reported here confirms the overall similarity of its alpha-beta-alpha architecture to that of the bacterial flavodoxins, but reveals differences in the position, number, and length of the helices relative to the central beta-sheet. The marked similarity between P450R-FMN and flavodoxins in the interactions between the FMN and the protein, indicate a striking evolutionary conservation of the FMN binding site. The P450R-FMN molecule has an unusual surface charge distribution, leading to a very strong dipole, which may be involved in docking cytochrome P450 into place for electron transfer near the FMN. Several acidic residues near the FMN are identified by mutagenesis experiments to be important for electron transfer to P4502D6 and to cytochrome c, a clear indication of the part of the molecular surface that is likely to be involved in substrate binding. Somewhat different parts are found to be involved in binding cytochrome P450 and cytochrome c.

Animals↗
PubMed1998

Fast eye movement initiation of ocular torsion in mesodiencephalic lesions.

Three patients with episodic ocular torsion and skew deviation due to mesodiencephalic lesions were studied by using binocular three-dimensional scleral search coils. The conjugate ocular torsion (upper pole of each eye rotating toward the side of the brainstem lesion) was initiated by a torsional fast eye movement. During prolonged episodes, torsional nystagmus was also present. Cessation of the ocular torsion and skew deviation occurred by slow eye movements with exponentially decreasing velocities in 2 patients, and by multiple fast torsional movements in 1 patient. In 1 patient, the abnormal eye movements were temporally linked to dystonic movements in the limbs on the side opposite the brainstem lesion. The occurrence of skew deviation with conjugate ocular torsion in brainstem lesions has been attributed to functional asymmetry in vestibular pathways responsible for the slow-phase compensatory eye movement response to roll. In comparison, the findings in our patients show that in mesodiencephalic lesions conjugate ocular torsion with skew deviation may be generated by torsional fast eye movements, indicating activation of the burst cells of the rostral interstitial nucleus of the medial longitudinal fasciculus.

Adult↗
PubMed1997

Problem-based learning at the University of Southern California School of Dentistry.

Responding to the recent Institute of Medicine report on dental education, the Center for Craniofacial Molecular Biology (CCMB) of the University of Southern California School of Dentistry has developed a parallel track program in dental education leading to the D.D.S. degree. This program was proposed in May of 1995, and the first class of twelve students was admitted in September of that year. Currently two classes are enrolled and plans to admit a further twelve students (Class of 2001) are in place. The educational strategy for this program is totally problem-based. Students work in groups of six with a faculty facilitator, not necessarily a content expert. Facilitators are largely drawn from the multidisciplinary pool of research faculty at the center. All learning is mediated through biomedical and biodental problem cases. No formal lectures or classes are scheduled. The learning of clinical dental skills is promoted through focussed dental patient simulations in which students review clinical charts, radiographs, medical reports and then explore identified, hands-on learning needs using patient simulators in a clinical context. Early patient exposure is obtained through dental office visits and other special patient clinics. Initial experience with this program suggests that the problem-based learning (PBL) students learn as well (if not better) than their traditional program peers and develop excellent group and cognitive analytical skills. The absence of a pool of dentally related biomedical cases suitable for a PBL program has necessitated the use of innovative approaches to their development and presentation. It is believed that this educational approach will produce dental clinicians equipped with the self-motivated, life-long learning skills required in the ever-changing world of bio-dental sciences in the twenty-first century.

California↗
PubMed1995

Trauma centers in a managed care environment.

Health care reform will affect the relationship of trauma centers to health maintenance organizations and other managed care plans. We studied Kaiser Permanente Medical Center (Kaiser) members admitted to the Trauma Center at San Francisco General Hospital (SFGH) to determine: (1) variables predicting transfer from SFGH to a Kaiser Hospital (repatriation), (2) the length of hospital stay (LOS), and (3) the cost of their care. The SFGH trauma registry provided data on 7,794 patients admitted before 1994. To investigate LOS, 89 Kaiser patients over 1 year were matched with non-Kaiser patients on age, maximum Abbreviated Injury Scale score (MAIS) by body region, Injury Severity Score (ISS), head injury severity, and blunt or penetrating injury and disposition. Kaiser patients were significantly younger, more likely to have blunt injury, and had a lower death rate. Significant predictors of repatriation were an MAIS score > or = 3, abdominal or extremity injury, and an ISS score of 26 to 40. The mean LOS for all Kaiser patients was 7.6 days, compared with 4.8 for controls (p = 0.20). However, mean LOS was significantly longer in repatriated Kaiser patients compared with controls (16 vs. 7.8 days, p < 0.0005). Kaiser reimbursement rates were comparable with commercial payors, but higher than others. A relatively small number of severely injured patients account for a large percentage of costly trauma care. Analyses of patient subsets are necessary for trauma centers to negotiate suitable relationships with managed care plans. A prospective study is needed to examine the cost efficiency of early transfer of managed care patients.

Adult↗
PubMed1993

Daytime alertness in patients with primary insomnia.

OBJECTIVE: In the absence of clear distinctions in alertness between patients with primary insomnia and normal subjects, the goal of this study was to identify psychometric and electrophysiological measures that would distinguish these two groups. METHOD: The daytime alertness of 20 primary insomnia patients and 20 normal subjects was investigated through their scores on a 26-item hyperarousal scale and measurement of auditory evoked potentials and alpha and nonalpha band EEG activity. Statistical analysis of the data included correlation of the hyperarousal scores and the electrophysiological measures. RESULTS: The hyperarousal scores showed clearly higher daytime alertness in the insomnia patients compared with the normal subjects. In addition, during wakefulness, the insomnia patients showed greater amplitudes of P1N1, a durable, intrinsic, late (cortical) component of the auditory evoked potential, as well as greater EEG activity across the frequency spectrum. The hyperarousal scores correlated positively with the amplitude of P1N1 at each of three sound intensities. CONCLUSIONS: To the authors' knowledge, this is the first study to offer evidence that patients with primary insomnia have objectively definable features during wakefulness that clearly distinguish them from normal subjects. The measurement of hyperarousal might be used to refine descriptions of insomnia populations in experimental studies.

Adult↗
PubMed1993

Apparent hydrocephalus and chronic multiple sclerosis: a report of two cases.

Generalised ventricular dilatation with or without cerebral atrophy is common in longstanding multiple sclerosis. This has been widely assumed to be due to periventricular white matter atrophy rather than true communicating hydrocephalus although it can be difficult to distinguish between these on radiological grounds. Here we report 2 chronic MS patients who had progressive dementia, gait disturbance and urinary incontinence and in whom neuroimaging, and in one case CSF infusion studies, suggested hydrocephalus. Both significantly improved following shunting procedures. We suggest that further study is required to investigate whether a significant proportion of patients with chronic MS and dilated ventricles have shunt-responsive hydrocephalus.

Cerebrospinal Fluid Shunts↗
PubMedDate not supplied

Crystallization and preliminary X-ray diffraction studies of human cytochrome P450 reductase.

The two functional domains of a cloned human fibroblast NADPH-cytochrome P450 reductase have been expressed in Escherichia coli and purified on the milligram scale for crystallization studies. One domain contains the cofactor FMN-binding site and the other contains the binding sites for cofactor FAD and substrate NADPH. Crystals of both domains have been obtained by the microbatch method. The crystals of the FMN domain belong to the monoclinic space group P21, with unit cell dimensions of a = 39.3 A, b = 51.5 A, c = 47.8 A, and beta = 105.7 degrees and have one molecule in the asymmetric unit. Diffraction data up to 2.3 A were collected with a merging residual on intensity of 9.3%. The crystals of the FAD/NADPH domain belong to the ortho-rhombic space group P212121 with unit cell dimensions of a = 55.9 A, b = 58.6 A, c = 131.1 A and have one molecule in the asymmetric unit. Diffraction data up to 2.6 A were collected with a merging residual on intensity of 8.0%.

Amino Acid Sequence↗