Multiple sclerosis of the spinal cord: magnetic resonance appearance

OBJECTIVE: To determine the MR appearance of spinal cord multiple sclerosis (MS) plaques in patients presenting with myelopathy by using a high-field (1.5 T) imager. MATERIALS AND METHODS: We studied 119 patients who underwent high-field (1.5 T) MR studies of the spinal cord for evaluation of myelopathy. All 119 patients were thought to have possible findings of spinal cord MS at the time of the MRI interpretation. RESULTS: Sixty-four plaques were studied in 47 patients with clinically definite MS and adequate quality MRI. Of these patients 68% had a single spinal cord plaque, 19% had two plaques, and 13% had three or more plaques. Sixty-two percent of the plaques occurred in the cervical spinal cord and most frequently involved the posterior (41%) and lateral (25%) aspects of the spinal cord. None of the 64 lesions involved the entire thickness of the spinal cord. The lesion length varied from 2 to 60 mm, with 84% of the lesions < 15 mm in length. The spinal cord diameter was unchanged in 84% of plaques, enlarged at the level of the lesion in 14%, and atrophic in 2%. Just over half (55%) of the plaques enhanced with intravenously administered gadolinium. Of the patients who received synchronous head and spinal cord examinations on the same day, 24% had normal findings on the MR study of the head. Follow-up spinal cord studies were available in nine patients. New lesions developed in two patients, while previously described lesions resolved. In three patients only new lesions developed. In four patients no change occurred in the existing number of cord plaques. CONCLUSION: Spinal cord demyelinating plaques present as well-circumscribed foci of increased T2 signal that asymmetrically involve the spinal cord parenchyma. Knowledge of their usual appearance may prevent unnecessary biopsy. An MR examination of the head may confirm the imaging suggestion of spinal cord demyelinating disease, because up to 76% of patients have abnormal intracranial findings. In the remaining 24% of cases in which the clinical diagnosis is not certain and MR findings in the head are negative, a follow-up spinal cord study is recommended, because these lesions evolve and change over time.     

Cyclophosphamide induced nail pigmentation

Cyclophosphamide therapy may occasionally cuase black pigmentation of the nails. We report five cases with this side effect and review the data on eleven cases in the literature. These changes start in the proximal nail beds and progress distally; on withdrawal of cyclophosphamide, clearing of the nail pigmentation proceeds in a similar fashion. The development of the nail pigmentation does not bear any relation to the primary condition for which cyclophosphamide was prescribed. The dose of the drug before the onset of pigmentation ranged from 1.2 to 12.3 g; the duration of treatment ranged from 10 days to 26 weeks. The mechanism of the nail pigmentation is unknown.     

Autoactivation of spore germination in mutant and wild type strains of Dictyostelium discoideum

Freshly formed wild type Dictyostelium discoideum spores are constitutively dormant, and thus require an activation treatment to germinate. Wild type spores may germinate without an activation treatment (autoactivate) after a period of ageing (maturation) in the intact fruiting body. Mutants have been isolated which autoactivate without the need for ageing. Autoactivation of mutant and aged wild type spores appears to occur by identical mechanisms; thus the mutation may involve premature maturation. Autoactivation is mediated by autoactivator substances released from spores as they spontaneously swell. These factors are readily chromatographed, and elute from a Biogel P2 column in three peaks of activity. One activity peak appears only after spores have begun to germinate. No autoactivator substances are released from heat activated spores. Autoactivation is sensitive to cychloheximide, and may result from altered spore permeability. Autoactivation is likely to be the mechanism of D. discoideum spore germination in nature.     

Massive air embolus to the left ventricle: diagnosis and monitoring by serial echocardiography

Air embolization is an unusual but potentially dangerous complication in left heart catheterization. Microbubbles can be detected with two-dimensional echocardiography, which is often used for this purpose during open heart and bypass surgeries. Permanent neurologic sequelae and hemodynamic collapse can result from embolization of air bubbles to the cerebral and coronary circulations, respectively. Hyperbaric oxygen is the treatment of choice for cerebral air embolization. We present a 39-year-old man who had air embolization during left ventriculography in the form of a large pocket of "pooled" air. The patient was treated with conservative therapy successfully. Two-dimensional transthoracic echocardiography was used to document the presence of the air and follow its dissolution.     

In vivo bone strain patterns in the zygomatic arch of macaques and the significance of these patterns for functional interpretations of craniofacial form

It has been proposed that the mammalian facial skeleton is optimized for countering or dissipating masticatory stress. As optimized load-bearing structures by definition exhibit maximum strength with a minimum amount of material, this hypothesis predicts that during chewing and biting there should be relatively high and near uniform amounts of strain throughout the facial skeleton. If levels of strain in certain areas of the facial skeleton are relatively low during these behaviors, this indicates that the amount of bone mass in these areas could be significantly reduced without resulting in the danger of structural failure due to repeated masticatory loads. Furthermore, and by definition, this indicates that these areas are not optimized for countering masticatory stress, and instead their overall morphology and concentration of bone mass has most likely been selected or influenced mainly by factors unrelated to the dissipation or countering of chewing and biting forces. An analysis of in vivo bone strain along the lateral aspect of the zygomatic arch of macaques indicates the clear absence of a high and near uniform strain environment throughout its extent. Instead, there is a steep strain gradient along the zygomatic arch, with the highest strains along its anterior portion, intermediate strains along its middle portion, and the lowest strains along its posterior portion. These data, in combination with earlier published data (Hylander et al., 1991), indicate that levels of functional strains during chewing and biting are highly variable from one region of the face to the next, and therefore it is unlikely that all facial bones are especially designed so as to minimize bone tissue and maximize strength for countering masticatory loads. Thus, the functional significance of the morphology of certain facial bones need not necessarily bear any important or special relationship to routine and habitual cyclical mechanical loads associated with chewing or biting. Furthermore, the presence of these steep strain gradients within the facial skeleton suggests that the amount of bone mass in the low-strain areas may be largely determined by factors unrelated to processes frequently referred to as "functional adaptation," or conversely, that the "optimal strain environment" of bone varies enormously throughout the facial skeleton (cf., Rubin et al., 1994). Based solely on anatomical considerations, it is likely that the zygomatic arch is bent in both the parasagittal and transverse planes and twisted about its long axis. Due to constraints on rosette position, the strain data are incapable of determining if one or more of these loading conditions predominate. Instead, the strain data simply provide limited support for the possible presence of all of these loading regimes. Finally, as the masseter muscle is concentrated along the anterior portion of the zygomatic arch and as the arch has fixed ends, the largest shearing forces and the largest bending and twisting moments are located along its anterior portion. This in turn explains why the largest strains are found along the anterior portion of the zygomatic arch.     

Organized cell swimming motions in Bacillus subtilis colonies: patterns of short-lived whirls and jets

The swimming motions of cells within Bacillus subtilis colonies, as well as the associated fluid flows, were analyzed from video films produced during colony growth and expansion on wet agar surfaces. Individual cells in very wet dense populations moved at rates between 76 and 116 microm/s. Swimming cells were organized into patterns of whirls, each approximately 1,000 microm2, and jets of about 95 by 12 microm. Whirls and jets were short-lived, lasting only about 0.25 s. Patterns within given areas constantly repeated with a periodicity of approximately 1 s. Whirls of a given direction became disorganized and then re-formed, usually into whirls moving in the opposite direction. Pattern elements were also organized with respect to one another in the colony. Neighboring whirls usually turned in opposite directions. This correlation decreased as a function of distance between whirls. Fluid flows associated with whirls and jets were measured by observing the movement of marker latex spheres added to colonies. The average velocity of markers traveling in whirls was 19 microm/s, whereas those traveling in jets moved at 27 microm/s. The paths followed by markers were aligned with the direction of cell motion, suggesting that cells create flows moving with them into whirls and along jets. When colonies became dry, swimming motions ceased except in regions close to the periphery and in isolated islands where cells traveled in slow whirls at about 4 microm/s. The addition of water resulted in immediate though transient rapid swimming (> 80 microm/s) in characteristic whirl and jet patterns. The rate of swimming decreased to 13 microm/s within 2 min, however, as the water diffused into the agar. Organized swimming patterns were nevertheless preserved throughout this period. These findings show that cell swimming in colonies is highly organized.     

Identification of PLCgamma-dependent and -independent events during fertilization of sea urchin eggs

At fertilization, sea urchin eggs undergo a series of activation events, including a Ca2+ action potential, Ca2+ release from the endoplasmic reticulum, an increase in intracellular pH, sperm pronuclear formation, MAP kinase dephosphorylation, and DNA synthesis. To examine which of these events might be initiated by activation of phospholipase Cgamma (PLCgamma), which produces the second messengers inositol trisphosphate (IP3) and diacylglycerol, we used recombinant SH2 domains of PLCgamma as specific inhibitors. Sea urchin eggs were co-injected with a GST fusion protein composed of the two tandem SH2 domains of bovine PLCgamma and (1) Ca2+ green dextran to monitor intracellular free Ca2+, (2) BCECF dextran to monitor intracellular pH, (3) Oregon Green dUTP to monitor DNA synthesis, or (4) fluorescein 70-kDa dextran to monitor nuclear envelope formation. Microinjection of the tandem SH2 domains of PLCgamma produced a concentration-dependent inhibition of Ca2+ release and also inhibited cortical granule exocytosis, cytoplasmic alkalinization, MAP kinase dephosphorylation, DNA synthesis, and cleavage after fertilization. However, the Ca2+ action potential, sperm entry, and sperm pronuclear formation were not prevented by injection of the PLCgammaSH2 domain protein. Microinjection of a control protein, the tandem SH2 domains of the phosphatase SHP2, had no effect on Ca2+ release, cortical granule exocytosis, DNA synthesis, or cleavage. Specificity of the inhibitory action of the PLCgammaSH2 domains was further indicated by the finding that microinjection of PLCgammaSH2 domains that had been point mutated at a critical arginine did not inhibit Ca release at fertilization. Additionally, Ca2+ release in response to microinjection of IP3, cholera toxin, cADP ribose, or cGMP was not inhibited by the PLCgammaSH2 fusion protein. These results indicate that PLCgamma plays a key role in several fertilization events in sea urchin eggs, including Ca2+ release and DNA synthesis, but that the action potential, sperm entry, and male pronuclear formation can occur in the absence of PLCgamma activation or Ca2+ increase.