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Biomedical subjects

M Boska

Publications and source records attributed to M Boska.

14 recordsLinked to original sources
PubMed2006

Valproic acid adjunctive therapy for HIV-associated cognitive impairment: a first report.

In vitro and animal model data demonstrate that valproic acid (VPA) can ameliorate HIV-associated neurotoxicity. The authors conducted a pilot 10-week placebo-controlled study of VPA 250 mg twice daily in 22 HIV-infected individuals with (n = 16) and without (n = 6) cognitive impairment. VPA was safe and well tolerated, with trends toward improved neuropsychological performance and brain metabolism in the impaired subjects.

AIDS Dementia Complex↗
PubMed2005

Coregistration of quantitative proton magnetic resonance spectroscopic imaging with neuropathological and neurophysiological analyses defines the extent of neuronal impairments in murine human immunodeficiency virus type-1 encephalitis.

Relatively few immune-activated and virus-infected mononuclear phagocytes (MP; perivascular macrophages and microglia) may affect widespread neuronal dysfunction during human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD). Indeed, histopathological evidence of neuronal dropout often belies the extent of cognitive impairment. To define relationships between neuronal function and histopathology, proton magnetic resonance spectroscopic imaging (1H MRSI) and hippocampal long-term potentiation (LTP) were compared with neuronal and glial immunohistology in a murine model of HIV-1 encephalitis (HIVE). HIV-1(ADA)-infected human monocyte-derived macrophages (MDM) were stereotactically injected into the subcortex of severe combined immunodeficient (SCID) mice. Sham-operated and unmanipulated mice served as controls. Seven days after cell injection, brain histological analyses revealed a focal giant cell encephalitis, with reactive astrocytes, microgliosis, and neuronal dropout. Strikingly, significant reductions in N-acetyl aspartate concentration ([NAA]) and LTP levels in HIVE mice were in both injected and contralateral hemispheres and in brain subregions, including the hippocampus, where neuropathology was limited or absent. The data support the importance of 1H MRSI as a tool for assessing neuronal function for HAD. The data also demonstrate that a highly focal encephalitis can produce global deficits for neuronal function and metabolism.

AIDS Dementia Complex↗
PubMed1999

T1 and magnetization transfer at 7 Tesla in acute ischemic infarct in the rat.

T1 and magnetization transfer at a field strength of 7 Tesla were used to discriminate between water accumulation and protein mobilization in tissue undergoing infarction. Twelve rats subjected to acute stroke via intralumenal suture occlusion of the middle cerebral artery, and 19 controls, were studied. In MRI studies to 6 hr post-ictus, serial data acquisition allowed the measurement of cerebral blood flow (CBF), apparent diffusion coefficient of water (ADCw), equilibrium magnetization (M0) and T1, and equilibrium magnetization and T1 under an off-resonance partial saturation of the macromolecular pool (Msat and T1sat). Using these parameters, the apparent forward transfer rate of magnetization between the free water proton pool and the macromolecular proton pool, k(fa), was calculated. Regions of interest (ROIs) were chosen using depressed areas in maps of the ADCw. T1 measurements in bovine serum albumin at 7T were not affected by the mobility of the macromolecular pool (P > 0.2), but magnetization transfer between free water and protein depended strongly on the mobility of the macromolecular pool (P < 0.001). For 6 hr after ictus, k(fa) uniformly and strongly decreased in the region of the infarct (P < 0.0001). Ratios (ischemic/non-ischemic) of parameters M0, Msat, T1, and T1sat all uniformly and strongly increased in the infarct. The ratio T1/T1sat in the region of infarction showed that a progressive accumulation of free water in the region of interest was the major (>80%) contribution to the decrease in k(fa). There also existed a small contribution due to changes at the water-macromolecular interface, possibly due to proteolysis (P = 0.005).

Acute Disease↗
PubMed1996

Optimal positioning for cervical immobilization.

STUDY OBJECTIVE: We hypothesized that optimal positioning of the head and neck to protect the spinal cord during cervical spine immobilization can be determined with reference to external landmarks. In this study we sought to determine the optimal position for cervical spine immobilization using magnetic resonance imaging (MRI) and to define this optimal position in a clinically reproducible fashion. METHODS: Our subjects were 19 healthy adult volunteers (11 women, 8 men). In each, we positioned the head to produce various degrees of neck flexion and extension. This positioning was followed by quantitative MRI of the cervical spine. RESULTS: The mean ratio of spinal canal and spinal cord cross-sectional areas was smallest at C6 but exceeded 2.0 at all levels from C2 to T1 (P < .05). At the C5 and C6 levels, the maximal area ratio was most consistently obtained with slight flexion (cervical-thoracic angle of 14 degrees) (P < .05). For a patient lying flat on a backboard, this corresponds to raising the occiput 2 cm. More extreme flexion or extension produced variable results. CONCLUSION: In healthy adults, a slight degree of flexion equivalent to 2 cm of occiput elevation produces a favorable increase in spinal canal/spinal cord ration at levels C5 and C6, a region of frequent unstable spine injuries.

Adult↗
PubMed1995

NMR imaging with shorted coaxial line probes.

At frequencies below 1 GHz, resonant sections of coaxial lines have long been used in CW-Electron Paramagnetic Resonance (EPR) with the sample placed at the position of maximum B1 at a short circuited end. Here, we show that because of the excellent separation of the B and E fields, the shield of the line can be removed in the region of the truncated end without greatly perturbing the RF properties of the line. The open region of the shield provides an aperture for local imaging in MRI. The B1 fields can be shaped by contouring the inner conductor and outer shield, and the image aperture is controlled by the shape of the shield cutout. The shield opening can range from a narrow longitudinal slit up to a full 360 degrees section that has only a few conducting strips of the shield remaining. Imaging with probes having shield diameters from 2 mm to 10 cm have been demonstrated. For imaging the useful depth is limited to approximately three to four times the probe's outer radius. Alternately, a relatively sharp cutoff at only a mm depth can be obtained by controlling the region of the shield removed, the RF power applied, and the probe diameter. The probes described here can be resonant or nonresonant. Because of the inherent broad bandwidth of the nonresonant truncated line probes, they have the potential for use in FT-EPR and FT-EPR imaging as well as other applications that require minimizing dead times.

Catheterization↗
PubMed1995

A novel topical probe for MRI: the flat, truncated line probe.

The construction and imaging characteristics of flat, truncated line probes (FTLPs) are described here. These probes illustrate a novel design of local probes for magnetic resonance imaging, with four major differences from conventional loop surface probes: (1) The B1 fields are directed perpendicular to the usual loop probes' direction. (2) The RF fringe electric fields are inherently shielded, which allows reduced loading from electrically lossy samples. (3) The homogeneity across the plane of the probe can be adjusted locally. And (4) when not used with tuning and matching circuits, a probe's local impedance can be set to match the RF line impedance. The probes are, in essence, a single loop significantly flattened with the outside conductor (away from the imaged object) wider than the inside conductor (against the imaged object). The probes are shaped so as to provide a homogeneous signal across the plane area of the probe. The signal intensity drops off faster than a loop of the same size. With a minimally loading phantom, along the midline normal to the surface, the S/N at the surface region is approximately 20% greater than a commercial probe (Phillips R2) of the same area dimensions, while at 5 cm depth, the S/N is lower. However, when used for imaging a body--again along the midline normal to the probe--the S/N at 5 cm depth is equal, and rises to approximately twice that of the Philips R2 probe at the surface.

Electric Impedance↗
PubMed1994

ATP production rates as a function of force level in the human gastrocnemius/soleus using 31P MRS.

Net forward adenosine triphosphate (ATP) production rates were calculated from 31P nuclear magnetic resonance spectroscopy (MRS) kinetic data collected with 1-8 s time resolution during isometric voluntary contractions of the human gastrocnemius/soleus muscle group. Volume normalized muscle output (Newtons/ml) was then divided by the calculated net ATP use (mM/s) to estimate the metabolic economy (ME) (Newtons.s/mumol ATP). The ATP production rates from anaerobic glycolysis (An Gly) and creatine kinase (CK) reactions are approximately half of the oxidative phosphorylation ATP production rates (Ox Phos) at the end of 90 s of isometric contractions for a series of force levels. However, ME was independent of the force level in these exercises. The correlation between MVC of healthy, trained subjects, and the maximal cross-sectional area of the gastrocnemius/soleus shows an average of 21.2 +/- 4.6 Newtons/cm2 (mean +/- SD, N = 15). This was measured using a foot pedal with a transducer measurement point 10.6 cm above the heel. [ADP] versus Ox Phos ATP production rate fits a Michaelis-Menten kinetic control equation with an offset (underestimation of Ox Phos) of 0.3 mM/s and a Km = 27 microM for ADP and a Vmax = 1.0 mM/s. This suggests that [ADP] is the controlling factor for mitochondrial function at the end of a 90 to 120 s isometric contraction in normal subjects at any force level. Quantitative measurements of the phosphorus metabolite concentrations were obtained from 20 individuals and these data are also reported.

Adenosine Triphosphate↗
PubMed1993

Dissociation of [H+] from fatigue in human muscle detected by high time resolution 31P-NMR.

Previous in vivo studies of skeletal muscle fatigue have demonstrated significant relationships between the decline of muscular force and changes in muscle metabolism. However, these studies performed measurements over relatively long time intervals or during steady state exercise, thereby obscuring rapid metabolic changes occurring at the onset of exercise and recovery. To overcome these limitations, fatigue of human calf musculature during sustained isometric foot plantar flexion was quantified continuously as the decline in maximal voluntary contraction force (MVC), while concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), intracellular free hydrogen ion (H+), and monovalent phosphate (H2PO4-) were simultaneously measured at 2-second intervals by 31P nuclear magnetic resonance. The first major finding was that [H+], which has been thought to be a mediator of muscle fatigue, actually declined during the first 10 seconds of exercise when force was declining and rose immediately postexercise, when force partially recovered. Second, the correlations of [H+], [H2PO4-] and Pi with MVC during the first minute of exercise were determined to be curvilinear and not linear as previously suggested. Furthermore, using either a linear or curvilinear regression model, [H2PO4-] and Pi demonstrated a closer correlation to MVC than [H+] during the first minute of exercise. Thus, these results reveal nuances in the relationships of MVC to metabolites previously undetected by low time-resolution measurements. These findings suggest that during sustained isometric exercise, rising [H+] is not likely to be the sole mechanism of muscle fatigue and are consistent with the view that a rise of Pi or [H2PO4-] is a major causation factor in force reduction.

Adolescent↗
PubMed1991

Estimating the ATP cost of force production in the human gastrocnemius/soleus muscle group using 31P MRS and 1H MRI.

Net ATP production rates in exercising human muscle were calculated from 31P MRS kinetic data collected with 1-8 s time resolution. During the exercise, the muscle output was measured using a force transducer. Muscle output (force/unit volume) is then divided by the calculated net ATP used to estimate the ATP cost of force production. These measurements have been performed using an exercise protocol of isometric maximum voluntary contraction of the gastrocnemius/soleus muscle group. Results show that by the end of 30 s of exercise, total ATP production and ATP cost of force production had stabilized and remained constant (within the measurement errors) until the end of the 2-min period. The results also demonstrate that either the ATP cost of force production in the human gastrocnemius/soleus is lower in the first second than at any other time in the 2-min window which was investigated, or that the ATP production is being underestimated at the later time points. These data on ATP production rates, and the data relating to ATP cost of force production in muscle will aid in understanding the causes of muscle failure as well as the progression and treatment of muscle disease.

Adenosine Triphosphate↗
PubMed1986

Reversible and irreversible effects of alkaline pH on Photosystem II electron-transfer reactions.

Incubation of highly active, O2-evolving PS II preparations at alkaline pH inhibits donor side electron-transfer reactions in two distinct fashions, one reversible the other irreversible. In both cases, O2 evolution is inhibited, with concomitant loss of the light-induced multiline and g = 4.1 EPR signals and an increased steady-state level of EPR Signal II induced by continuous illumination. However, the inhibition that is observed between pH 7.0 and 8.0 is readily reversible by resuspension at low pH, while above pH 8.0 the effect is irreversible. In addition, under repetitive flash conditions the ms decay kinetics remains largely unchanged at pH less than or equal to 8.0 but shows about a 2-fold increase in amplitude and is slowed at pH above 8.0. The irreversible component of inhibition most likely can be attributed to the loss of Mn and the 16, 24 and 33 kDa proteins. The reversible component may be mediated by displacement of Cl- from an anion-binding site by OH- or by titration of ionizable groups on the protein(s) associated with water-splitting. We propose that the reversible inhibition blocks electron transfer between the O2-evolving complex and an intermediate which serves as the direct donor to Signal II, while the irreversible inhibition blocks the reduction of Signal II by this intermediate donor species.

Chlorophyll↗
PubMed1985

The effect of mono- and divalent salts on the rise and decay kinetics of EPR signal II in Photosystem II preparations from spinach.

The rise and decay kinetics of EPR signal II have been used to probe the organization of the donor side of Photosystem II (PS II) before and after extraction of PS II preparations with high concentrations of salt. 800 mM NaCl or 500-800 mM NaBr substantially depletes the preparations of the 16 and 24 kDa proteins and decreases the steady-state rate of O2-evolution by 70-80% from control rates. These treatments do not largely alter the decay kinetics of Signal II; the rise kinetics remain in the instrument limited time range (2 microseconds or less) during the first 8-12 flashes. Treating PS II preparations with 800 mM CaCl2 removes the 16, 24 and 33 kDa proteins with at least 95% inhibition of the steady-state rates of O2 evolution. The additional removal of the 33 kDa polypeptide decreases the rates of oxidation and rereduction of Z, the species responsible for Signal II. Preparations treated with either mono- or divalent salts show a steady-state light-induced increase in Signal II similar to that seen in Tris-washed samples. Such a steady-state increase indicates that the rate of electron transport from water to Z is greatly decreased or blocked. The data are interpreted within a model in which there is an intermediate electron carrier between the O2 evolving complex and Z.

Calcium Chloride↗