Search PubMedSearch

Biomedical subjects

M S Cohen

Publications and source records attributed to M S Cohen.

At least 19 recordsLinked to original sources

Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.

Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter T1-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P less than 0.001) of 1.8% +/- 0.8% (GE) and 1.8% +/- 0.9% (IR) was observed in the primary visual cortex (V1) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 +/- 2.2 s for the GE images and 8.9 +/- 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (M1) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatial-temporal window onto individual brain physiology.

Animals

Spin trapping evidence for myeloperoxidase-dependent hydroxyl radical formation by human neutrophils and monocytes.

Using the electron spin resonance/spin trapping system, 4-pyridyl 1-oxide N-tert-butylnitrone (4-POBN)/ethanol, hydroxyl radical was detected as the alpha-hydroxyethyl spin trapped adduct of 4-POBN, 4-POBN-CH(CH3)OH, from phorbol 12-myristate 13-acetate-stimulated human neutrophils and monocytes without the addition of supplemental iron. 4-POBN-CH(CH3)OH was stable in the presence of a neutrophil-derived superoxide flux. Hydroxyl radical formation was inhibited by treatment with superoxide dismutase, catalase, and azide. Treatment with a series of transition metal chelators did not appreciably alter 4-POBN-CH(CH3)OH, which suggested that hydroxyl radical generation was mediated by a mechanism independent of the transition metal-catalyzed Haber-Weiss reaction. Kinetic differences between transition metal-dependent and -independent mechanisms of hydroxyl radical generation by stimulated neutrophils were demonstrated by a greater rate of 4-POBN-CH(CH3)-OH accumulation in the presence of supplemental iron. Detection of hydroxyl radical from stimulated monocyte-derived macrophages, which lack myeloperoxidase, required the addition of supplemental iron. The addition of purified myeloperoxidase to an enzymatic superoxide generating system resulted in the detection of hydroxyl radical that was dependent upon the presence of chloride and was inhibited by superoxide dismutase, catalase, and azide. These findings implicated the reaction of hypochlorous acid and superoxide to produce hydroxyl radical. 4-POBN-CH(CH3)OH was not observed upon stimulation of myeloperoxidase-deficient neutrophils, whereas addition of myeloperoxidase to the reaction mixture resulted in the detection of hydroxyl radical. These results support the ability of human neutrophils and monocytes to generate hydroxyl radical through a myeloperoxidase-dependent mechanism.

Electron Spin Resonance Spectroscopy

An aqueous gastrointestinal contrast agent for use in echo-planar MR imaging.

Four volunteers were imaged with echo-planar imaging before and after ingesting a dilute barium preparation. The contrast material improved bowel visibility by increasing lumen signal intensity, without increasing noise. Long T2 gastrointestinal contrast material can be used in T2-weighted imaging when motion artifacts are suppressed by ultrashort acquisitions.

Administration, Oral

Fracture-dislocation of the elbow with inferior radioulnar dislocation: a variant of the Essex-Lopresti injury.

We describe two patients with an Essex-Lopresti fracture dislocation in association with a dislocation of the elbow. This combination of injuries has not been previously reported. The Essex-Lopresti fracture is a rare injury, and the associated distal radioulnar dislocation is often missed. Meticulous radiographic evaluation of the wrist, including dynamic stress radiographs of the forearm, can lead to an earlier diagnosis and improved care of these patients.

Adult

Treatment of scapholunate dissociation by ligamentous repair and capsulodesis.

We believe that direct scapholunate ligamentous repair, supported by a dorsal radioscaphoid capsulodesis, should be considered for the treatment of most scapholunate dissociations when there is no osteoarthritis, regardless of the time that has elapsed since injury. We treated 24 patients by this technique between 1972 and 1988. The records of 21 were available for study. Average time from injury to surgical treatment was 17 months (range, 1 to 84 months). Results were evaluated clinically and by means of patient questionnaire and x-ray films. The significant change in range of motion was a loss of palmar flexion, which averaged 11.5 degrees. Grip strength, pain, and x-ray appearance improved in all cases. Only one patient had to change occupations after surgery because of wrist symptoms. Three had minimal x-ray degenerative changes, which did not result in increased pain or in loss of motion and grip strength. There were no complications.

Adolescent

Interaction of lactoferrin and lipopolysaccharide (LPS): effects on the antioxidant property of lactoferrin and the ability of LPS to prime human neutrophils for enhanced superoxide formation.

Lactoferrin is a 77-kDa iron-binding protein to which a wide variety of divergent biologic functions have been ascribed. It has recently been reported that lactoferrin interacts with bacterial lipopolysaccharide (LPS) in such a fashion as to affect the binding of lactoferrin to myeloid cells. Two other potential interactions of LPS and lactoferrin were explored. Lactoferrin prevents hydroxyl radical formation by binding iron, even at low pH. Lactoferrin inhibited iron-catalyzed formation of hydroxyl radical in the presence of LPS at pH 7.4 and 4.5. Low concentrations of LPS can be used to "prime" neutrophils toward enhanced function, such as formation of stimulated superoxide anion. Lactoferrin inhibited LPS priming of neutrophils if LPS contamination of the protein (provided by commercial suppliers) was first reduced. Inhibition of LPS priming was observed whether apolactoferrin or iron-saturated lactoferrin was used. Similar inhibition of LPS priming was observed when neutrophils were incubated with other serum proteins (e.g., albumin, apotransferrin, or iron-saturated transferrin). These results show that LPS should not be expected to affect the free radical biology of lactoferrin, which is a crucial physiologic function of this protein. However, lactoferrin inhibits LPS priming, and this effect requires consideration in experimental models of inflammation.

Apoproteins

The medical orbital strut in the prevention of postdecompression dystopia in dysthyroid ophthalmopathy.

Ocular dystopia with inferomedial displacement of the globe is an unusual but well-recognized complication of bony orbital decompression. It is caused by displacement of the muscle cone and orbital connective tissue system into the maxillary and ethmoidal sinuses. We illustrate a surgical variation of bony orbital decompression leaving intact a strut of bone at the maxillary-ethmoid junction. This bony strut reduces inferomedial displacement of the muscle cone and provides a medial supporting "ledge" in cases requiring late orbital reconstruction.

Eye Diseases

Eyelid reconstruction with hard palate mucosa grafts.

Hard palate mucosa grafts are an excellent replacement for tarsus and conjunctiva in eyelid reconstruction. Twenty-five eyelids from 18 patients underwent eyelid reconstruction using hard palate mucosa grafts. Patients were treated for a variety of disorders including postblepharoplasty lower eyelid retraction, cicatricial entropion, eyelid retraction secondary to thyroid eye disease, and lagophthalmos following surgery for paralytic ptosis. Surgical results were evaluated, grafts were measured for postoperative shrinkage, and donor site healing was recorded. Several patients had hard palate biopsy specimens evaluated. One of these patients also had a graft biopsied after it had been in place for 3 months. A review of hard palate anatomy and histology and a discussion of surgical technique are presented.

Adult

Magnetic resonance imaging mapping of brain function. Human visual cortex.

Magnetic resonance imaging (MRI) studies of human brain activity are described. Task-induced changes in brain cognitive state were measured using high-speed MRI techniques sensitive to changes in cerebral blood volume (CBV), blood flow (CBF), and blood oxygenation. These techniques were used to generate the first functional MRI maps of human task activation, by using a visual stimulus paradigm. The methodology of MRI brain mapping and results from the investigation of the functional organization and frequency response of human primary visual cortex (V1) are presented.

Brain Mapping

Efficacy of double gloving as a protection against blood exposure in dermatologic surgery.

Double gloving has been widely suggested as a means of decreasing exposure to blood and other body fluids. However, most dermatologists do not routinely follow this practice when performing surgical procedures because it reduces manual dexterity and increases costs. To determine whether double gloving should be routinely practiced in dermatologic surgery, pairs of sterile surgical gloves worn during weekly UCLA dermatologic surgery clinics were collected over a period of 3 months and examined for perforations. The procedures gloves were used for ranged from excision of benign lesions, lasting 15 minutes, to hair transplants, lasting 3 hours. Upon completion of the procedures, 8 (5.5%) of 144 pairs of single gloves, 2 (3.7%) of 54 pairs of double inner gloves, and 3 (5.5%) of 54 pairs of double outer gloves were found to have perforations. There were no instances of both the double outer and the double inner gloves having perforations when worn on the same hand. This suggests that double gloving offers a protective advantage by providing extra protection for both the surgeon and the patient during dermatologic surgery.

Blood

Response of Pseudomonas aeruginosa to pyocyanin: mechanisms of resistance, antioxidant defenses, and demonstration of a manganese-cofactored superoxide dismutase.

Pseudomonas aeruginosa produces a blue pigment, pyocyanin. Pyocyanin is a redox-active phenazine compound that kills mammalian and bacterial cells through the generation of reactive oxygen intermediates. We examined the mechanisms by which P. aeruginosa resists pyocyanin. [14C]pyocyanin was taken up by both Escherichia coli and P. aeruginosa, though more slowly by the latter. Cyanide-insensitive respiration, used as an indicator of intracellular superoxide and/or hydrogen peroxide production, was 50-fold less in pyocyanin-treated P. aeruginosa than in E. coli. P. aeruginosa showed less cyanide-insensitive respiration than E. coli upon exposure to other redox-active compounds (paraquat, streptonigrin, and plumbagin). Electron paramagnetic resonance spectrometry and spin trapping showed that P. aeruginosa generated less pyocyanin radical and superoxide than E. coli. Cell extracts from E. coli contained an NADPH:pyocyanin oxidoreductase which increased the rate of reduction of pyocyanin by NADPH. Conversely, cell extracts from P. aeruginosa contained no NADPH:pyocyanin oxidoreductase activity and actually decreased the rate of pyocyanin-mediated NADPH oxidation. Antioxidant defenses could also reduce the sensitivity of P. aeruginosa to pyocyanin. Under culture conditions of limited phosphate, both pyocyanin production and catalase activity were enhanced. Superoxide dismutase activity was also increased under low-phosphate conditions. When cells were grown in a high-phosphate succinate medium, P. aeruginosa formed a previously described iron-superoxide dismutase as well as a manganese-cofactored superoxide dismutase. These results demonstrate that P. aeruginosa resists pyocyanin because of limited redox cycling of this compound and that under conditions favoring pyocyanin production, catalase and superoxide dismutase activities increase.

Catalase

Techniques for high-resolution echo-planar MR imaging of the pancreas.

Recent technical advances in echo-planar magnetic resonance (MR) imaging prompted an investigation of these new techniques in pancreatic MR imaging and evaluation of bowel lumen enhancement with an aqueous bowel contrast agent. In 42 subjects (36 healthy, six with pancreatic disease), various T1-weighted inversion-recovery and T2-weighted spin-echo fat-suppressed pulse sequences were assessed with an echo-planar technique implemented with a modified clinical MR imager. Single-excitation imaging (echo time, 26 msec) provided a higher (P less than .05) signal-to-noise ratio than did conventional spin-echo and all other echo-planar techniques. In 13 (72%) of 18 healthy subjects who did not undergo administration of the contrast agent, the entire pancreas was distinguished from adjoining bowel. In all 18 subjects who underwent contrast-enhanced imaging, a significantly greater (P less than .05) intraluminal signal intensity was apparent with all echo-planar pulse sequences and the entire pancreas was identified. In six patients with pancreatic disease, lesions could be identified by their difference in signal intensity.

Barium Sulfate

Brain parenchyma motion: measurement with cine echo-planar MR imaging.

With echo-planar magnetic resonance (MR) imaging, the authors measured the intrinsic pulsatile motion of brain parenchyma. Phase-sensitive, electrocardiography-gated, two-dimensional cine images were acquired throughout the cardiac cycle by using a spin-echo, blipped echo-planar MR pulse sequence. Transverse and coronal planes were obtained in 14 healthy volunteers. Corrections were made for gross head motion. Brain motion consisted of a rapid displacement in systole, with a slow diastolic recovery. The motion occurred chiefly in the cephalocaudal and lateral directions; the anteroposterior motions were relatively small. Cephalocaudal velocities increase with proximity to the foramen magnum. The lateral motion is mainly a compressive motion of the thalami. Brain parenchymal velocities were as high as 2 mm/sec caudally in the brain stem and 1.5 mm/sec medially in the thalami. Net parenchymal excursions were at most 0.5 mm. Phase-based echo-planar velocity measurements agreed well with echo-planar Fourier velocity zeugmatography measurements and were consistent with reported values. Velocity mapping with echo-planar imaging offers a rapid and flexible method of assessing the pulsation velocities of the human brain.

Adult

Regulation of catalase in Neisseria gonorrhoeae. Effects of oxidant stress and exposure to human neutrophils.

We studied the effects of oxidant stress on the catalase activity and hydrogen peroxide sensitivity of Neisseria gonorrhoeae. N. gonorrhoeae is an obligate pathogen of man that evokes a remarkable but ineffective neutrophil response. Gonococci make no superoxide dismutase but express high catalase activity. Gonococcal catalase activity increased threefold when organisms were subjected to 1.0 mM hydrogen peroxide. This increase in catalase activity was marked by a parallel increase in protein concentration recognized by a rabbit polyclonal antibody raised against the purified gonococcal enzyme. Catalase was primarily localized to the gonococcal cytoplasm in the presence or absence of stress; only a single isoenzyme of catalase could be identified. Exposure of gonococci to neutrophil-derived oxidants was accomplished by stimulating neutrophils with phorbol myristate acetate or by using gonococcal Opa variants that interacted with neutrophils with different degrees of efficiency. Gonococci exposed to neutrophils demonstrated a twofold increase in catalase activity in spite of some reduction in viability. Exposure of gonococci to 1.0 mM hydrogen peroxide made the organisms significantly more resistant to higher concentrations of hydrogen peroxide and to neutrophils than control organisms. These results suggest that catalase is an important defense for N. gonorrhoeae during attack by human neutrophils. The rapid response of this enzyme to hydrogen peroxide should be taken into consideration in studies designed to evaluate the interaction between neutrophils and gonococci.

Catalase

Fracture of the trapezial ridge.

The trapezial ridge is a longitudinal projection of bone on the palmar surface of the trapezium and serves as an attachment for a portion of the transverse carpal ligament. It can be fractured from a fall onto the outstretched palm. Presented here is a case report of a young woman who sustained a fracture of the trapezial ridge. Point tenderness was a key initial symptom. Standard anteroposterior, lateral, and oblique roentgenograms did not demonstrate the fracture, and the diagnosis was repeatedly missed. The carpal tunnel view was obtained seven weeks after the original injury and showed a nondisplaced fracture through the trapezial ridge. Cast immobilization initiated at that time was not successful in obtaining fracture union. The delay in diagnosis and subsequent nonunion resulted in chronic discomfort and weakness of pinch and grasp. Careful clinical examination for point tenderness over the palmar surface of the trapezium and proper roentgenographic analysis should minimize delays in diagnosis and treatment of this fracture.

Adult

Uptake of lactoferrin by mononuclear phagocytes inhibits their ability to form hydroxyl radical and protects them from membrane autoperoxidation.

Human mononuclear phagocytes do not contain the iron-binding protein lactoferrin that we have previously demonstrated inhibits the potential for human neutrophils to generate hydroxyl radical in the presence of an exogenous iron catalyst of the Haber-Weiss reaction. Previous work by other investigators has suggested that mononuclear phagocytes (monocytes and monocyte-derived macrophages (MDM] have the capacity to bind exogenous lactoferrin via lactoferrin-specific membrane surface receptors. Accordingly, we examined the possibility that uptake of iron-free (apo) lactoferrin by human mononuclear phagocytes could play a role in limiting the potential for generation of hydroxyl radical during the monocyte/MDM respiratory burst. When monocytes or MDM were incubated in the presence of apo-lactoferrin, cell-associated lactoferrin increased in proportion to the concentration of lactoferrin provided. Similar results were obtained with iron-loaded (diferric) milk lactoferrin. Consistent with the in vivo importance of these findings, we found that lactoferrin was intimately associated with human alveolar macrophages obtained by bronchoalveolar lavage. The fucose polymer fucoidan inhibited lactoferrin uptake whereas exogenous transferrin or MDM exposure to IFN-gamma was without effect. Scatchard binding analysis confirmed the presence of a lactoferrin-specific receptor with a calculated kDa of 3.56 x 10(-6) M and 3.4 x 10(7) binding sites per cell. Subcellular fractionation studies indicated that twofold more of the lactoferrin which became cell-associated over the 1-h incubation time could be found in the cytoplasmic fraction compared to the plasma membrane-containing fraction, consistent with previous evidence by others for internalization of lactoferrin by mononuclear phagocytes. When lactoferrin-loaded monocytes/MDM were incubated in lactoferrin-free media, evidence for release of lactoferrin was obtained by SDS-PAGE and immunoblot analysis, suggesting the presence of a recyclable pool of cell-associated lactoferrin. To assess the impact of lactoferrin loading on monocyte/MDM hydroxyl radical formation, lactoferrin-loaded phagocytes were stimulated with PMA in the presence of catalytic iron. Hydroxyl radical generation by lactoferrin-loaded cells was decreased to about 50% of control cells. Similarly, monocytes that had been lactoferrin-loaded demonstrated a 28% decrease in autooxidation of their membrane when stimulated in the presence of catalytic iron. These data suggest that lactoferrin binding may play an important role in maintaining optimal mononuclear phagocyte function and protecting adjacent tissue from untoward phagocyte-associated hydroxyl radical generation.

Cell Membrane

Functional mapping of the human visual cortex by magnetic resonance imaging.

Knowledge of regional cerebral hemodynamics has widespread application for both physiological research and clinical assessment because of the well-established interrelation between physiological function, energy metabolism, and localized blood supply. A magnetic resonance technique was developed for quantitative imaging of cerebral hemodynamics, allowing for measurement of regional cerebral blood volume during resting and activated cognitive states. This technique was used to generate the first functional magnetic resonance maps of human task activation, by using a visual stimulus paradigm. During photic stimulation, localized increases in blood volume (32 +/- 10 percent, n = 7 subjects) were detected in the primary visual cortex. Center-of-mass coordinates and linear extents of brain activation within the plane of the calcarine fissure are reported.

Blood Volume