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Biomedical subjects

J T Keller

Publications and source records attributed to J T Keller.

At least 19 recordsLinked to original sources

Tumors of the lateral wall of the cavernous sinus.

The lateral dural wall of the cavernous sinus is composed of two layers, the outer dural layer (dura propria) and the inner membranous layer. Tumors arising from the contents of the lateral dural wall are located between these two layers and are classified as interdural. They are in essence extradural/extracavernous. The inner membranous layer separates these tumors from the venous channels of the cavernous sinus. Preoperative recognition of tumors in this location is critical for selecting an appropriate microsurgical approach. Characteristics displayed by magnetic resonance imaging show an oval-shaped, smooth-bordered mass with medial displacement but not encasement of the cavernous internal carotid artery. Tumors in this location can be resected safely without entering the cavernous sinus proper by using techniques that permit reflection of the dura propria of the lateral wall (methods of Hakuba or Dolenc). During the last 5 years, the authors have identified and treated five patients with interdural cavernous sinus tumors, which included two trigeminal neurinomas arising from the first division of the fifth cranial nerve, two epidermoid tumors, and one malignant melanoma presumed to be primary. The pathoanatomical features that make this group of tumors unique are discussed, as well as the clinical and radiological findings, and selection of the microsurgical approach. A more favorable prognosis for tumor resection and cranial nerve preservation is predicted for interdural tumors when compared with other cavernous sinus tumors.

Adult

Peptidergic and serotoninergic innervation of the rat dura mater.

The peptidergic and serotoninergic innervation of the rat dura mater was investigated by reacting dural wholemounts immunohistochemically with antibodies to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and serotonin (5-HT). CGRP and SP innervations of the dura were robust and the patterns of distribution of these neuropeptides were essentially the same. The majority of the fibers were perivascular and distributed to branches of the anterior and middle meningeal arteries and to the superior sagittal and transverse sinuses. Other CGRP/SP fibers appeared to end "free" within the dural connective tissue. NPY-immunoreactive fibers were extremely numerous and also distributed heavily to the branches of the meningeal arteries, the venous sinuses, and to the dural connective tissue. The pattern of NPY innervation resembled in many ways that of CGRP/SP; however, NPY innervation of the sinuses was greater and NPY perivascular fibers supplying the meningeal arteries formed more intimate contacts with the walls of the vessels. The pattern of VIP innervation was, in general, similar to that observed for the three previous neuropeptides; however, the overall density was considerably less. Small to moderate numbers of serotoninergic nerve fibers were observed in some, but not all, of the duras processed for 5-HT. The latter fibers were almost exclusively perivascular in distribution. Dural mast cells were prominently stained in the 5-HT preparations because of their serotonin content. Mast cells were also labeled in a nonspecific fashion in some of the tissues reacted immunohistochemically for neuropeptides; some of them were located in close apposition to passing nerve fibers. This study represents, to our knowledge, the first comprehensive work on the peptidergic and serotoninergic innervation of the mammalian dura mater. The results should increase our understanding of the roles that these fibers play in normal dural physiology and of their potential interactions in the pathogenesis of vascular headache.

Animals

Somatotopic distribution of corneal afferent neurons in the guinea pig trigeminal ganglion.

The size and somatotopic distribution of corneal afferent neurons in the guinea pig trigeminal ganglion were determined using a retrograde axonal tracing technique. Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was applied to the central cornea of the guinea pig and the animals were perfusion-fixed 48 h later. In addition, a preliminary study examined corneal afferent neurons in two animals latently infected with the herpes simplex virus by corneal inoculation. The majority of WGA-HRP-labelled neurons were located in the ophthalmic division of the ipsilateral ganglion. A clear dorsoventral somatotopic arrangement of labelled corneal afferent neurons was noted. The size of the neurons averaged 23 microns and the number of cells per ganglion averaged 205. By contrast, the number of labelled neurons in latently infected ganglia averaged less than 50. No size or morphological distinctions could be made between neurons from uninfected or latently infected ganglia. The results of this study have provided for the first time the precise location and somata diameter of primary afferent corneal neurons within the guinea pig trigeminal ganglion.

Animals

Linear arrays of homogeneous mast cells in the dura mater of the rat.

Using fluorescence histochemistry, 5-HT, histamine and heparin were colocalized in a large population of cells in the dura mater thereby identifying them as mast cells. In addition, because these cells were highly sensitive to compound 48/80 and were densely packed with granules of a consistent density, they were identified specifically as 'connective tissue' mast cells. Other types of mast cells, i.e. 'mucosal' or 'neurolipomastocytes', were not present in the rat dura mater. 5-HT immunohistochemistry was the best technique for demonstrating that there were populations of mast cells, one associated with each of the two layers of dura. Although shaped differently the type of mast cell in each layer was the same. It was observed that mast cell shape is dependent on the contiguity, density and orientation of its surrounding elements, not its type. In general, mast cells in the outer layer were aligned parallel to the middle meningeal artery and those in the inner layer were parallel to trigeminal nerve branches that coursed obliquely across the middle meningeal artery. Examination of cross-sections of dura revealed that most mast cells also were aligned at the interface between the two dural layers. The linear orientation of mast cells in two planes of each layer suggests a programmed lamellar seeding of these cells during development of the dura. This study also demonstrated that the majority of dural mast cells were more closely related to other connective tissue elements than to blood vessels and nerves. These results (1) are compatible with the suggestion that dural mast cells play a non-obligatory role in the neuroinflammatory response, (2) leave open to question the role of the dural mast cell in headache or the regulation of blood flow, and (3) support evidence that dural mast cells play an important role in connective tissue related functions, e.g. development, inflammatory response to injury and wound repair.

Animals

Influence of the sympathetic nervous system as well as trigeminal sensory fibres on rat dural mast cells.

The dura mater has attracted considerable attention as an exquisitely sensitive tissue implicated as playing a role in various cephalalgias including vascular headache. Because of the potential clinical impact of the relationship/interaction of neural elements and mast cells the influence of sensory and autonomic nerve fibres on mast cells of the rat dura mater was studied. The trigeminal or superior cervical ganglion was electrically stimulated and the mast cells were examined. Wholemount supratentorial dural preparations were stained using berberine sulphate and the number of mast cells with intact vs dispersed granules counted. Unilateral stimulation of either ganglia resulted in a statistically significant increase in the percentage of mast cells with dispersed granules ipsilateral to the side of stimulation. These results support our idea that in addition to the trigeminal system the sympathetic nervous system must be considered as playing a role in the oedema pathophysiology of vascular headache.

Animals

The Dolenc technique for cavernous sinus exploration (cadaveric prosection). Technical note.

This report describes a surgical approach to the cavernous sinus. Based on the work of Parkinson, Dolenc, and other pioneering investigators, a comprehensive surgical approach for the treatment of lesions of the cavernous sinus is distilled and presented in 12 simple steps. The approach to surgical exploration of this region is divided into an extradural and intradural phase, each with six steps. The bony, neural, and/or vascular structures of each step are discussed. These steps may be used in their entirety for total exploration of the cavernous sinus, but also in part for lesions that involve only limited regions of the cavernous sinus. Either by design or circumstance, every intracranial neurosurgeon will eventually be led to the cavernous sinus region, and a clear understanding of cavernous sinus anatomy should be part of their armamentarium.

Cadaver

Sympathetic innervation of the supratentorial dura mater of the rat.

The origin, density, and distribution of sympathetic nerve fibers in the supratentorial dura mater of the rat were examined in detail in the current study by using wheat germ agglutinin horseradish peroxidase (WGA-HRP) retrograde tracing procedures, glyoxylic acid-induced fluorescence, and dopamine beta-hydroxylase (DBH) immunocytochemical staining of dural whole mount preparations. Application of WGA-HRP to the superior sagittal sinus and adjacent areas of the supratentorial dura mater labeled numerous neurons in each of the left and right superior cervical ganglia. Glyoxylic acid and DBH immunocytochemical staining of fixed dural whole mount preparations revealed prominent plexuses of sympathetic nerves about the middle meningeal artery and its branches, about the superior sagittal and transverse sinuses, and "free" within the dura mater, i.e., apparently unassociated with any vasculature. Significantly, in all of these areas, the density of sympathetic innervation revealed in this study was considerably greater than that previously demonstrated by other workers. An impressive population of mast cells also was observed within the dura mater of the glyoxylic acid-treated preparations. The majority of these cells were perivascular; however, a significant number were also present within the dura unrelated to the vasculature, and occasional cells were seen in close apposition to fluorescent sympathetic nerve fibers. Taken together, the identification of a robust sympathetic plexus and prominent mast cell population associated with a dura mater that also receives significant sensory projections from the trigeminal system raises interest regarding the functional interactions of these elements. These observations warrant further consideration regarding their role in the pathogenesis of vascular headache and head pain.

Adrenergic Fibers

Repair of spinal dural defects with vicryl (polyglactin 910) mesh.

This study examined and compared the effectiveness of woven vicryl (polyglactin 910) mesh and lyophilized cadaver dura (Lyodura) for the repair of spinal dural defects. A woven vicryl mesh was used to repair spinal dural defects in 16 mongrel dogs. As an internal control, all animals had a separate dural incision that was closed with 9-0 vicryl suture. Animals were killed, and results were evaluated at 4, 8, 12, and 24 weeks. The repair of dural defects was achieved in all animals, and there were no cases of pseudo-meningocele formation, cerebrospinal fluid leakage, or postoperative infection. The vicryl mesh served as a latticework for formation of a neodural membrane. Inflammatory or reactive response to vicryl mesh was minimal, and no adhesion to underlying neural structures was noted. The neodural membrane formed in the animals in which lyophilized dura was employed was usually thicker than those in which vicryl mesh was used and was associated with thick arachnoid-neural adhesions in two of eight animals. We believe vicryl mesh is a suitable dural substitute and offers promise for use in clinical situations.

Animals

Secondary structure of 11 S globulin in aqueous solution investigated by FT-IR derivative spectroscopy.

Secondary structure of 11 S globulin, a major storage protein of soybean seeds, has been investigated in aqueous solution by FT-IR spectroscopy. Conformational changes in the native protein upon thermal and chemical denaturation have been monitored by observing changes in the frequency position and peak intensity of the various bands. The frequency of the Amide I band of the native protein shifts by 4 cm-1 from 1,643 cm-1 to 1,647 cm-1 when denatured, while the corresponding intensity of the Amide I band compared to the native protein, decreases by 30 and 67%, respectively, for the urea and thermally denatured proteins, indicating gross conformational changes in the secondary structure. Trifluoroethanol, an alpha-helix promoter shifts the Amide I band from 1,643 cm-1 to 1,651 cm-1, typical of alpha-helix, with a corresponding increase in intensity by 14% relative to the native protein. Derivative spectroscopy, allowing resolution of overlapping bands, shows that the native protein mainly consists of beta-sheet, beta-turns and disordered structure with very little alpha-helix. On denaturation, beta-sheet disappeared almost completely with urea, while this is less so with thermal denaturation.

Amides

A technique for monitoring mammalian cell growth and inhibition in situ via Fourier transform infrared spectroscopy.

A single culture of Chinese hamster ovary cells was grown on germanium attenuated total reflectance (ATR) crystals and continuously monitored in situ via ATR/Fourier transform infrared (FT-IR) spectroscopy for approximately 60 h. The cells were seeded into a specially designed flow cell which controlled physiological conditions, flow rate, and addition of growth medium or metabolic inhibitors. Infrared spectra were taken at 20-min intervals until a confluent monolayer was formed. Several strong bands are evident in the spectra which can be generally ascribed to molecular features of cellular components. Cell growth kinetics were measured as a function of infrared band intensity over time and exhibited the normal lag phase, logarithmic growth, and stationary phase on reaching confluence. Spectra of growing cells, normalized to the area under the spectral region 1800-1000 cm-1, were subtracted from reference spectra of confluent cells at 60 h. Difference spectra showed that the largest differences were observed between confluent cells and cells in early growth stages. Differences may reflect cell morphological changes, biochemical activity, and degree of ATR crystal exposure to the bulk medium. ATR/FT-IR spectroscopy of living Chinese hamster ovary cells was also used in a toxicological study to monitor the effects of hydroxyurea, an inhibitor of DNA synthesis. Delayed growth was observed in the cell growth curve of the hydroxyurea-treated cells during the course of treatment as compared to the control culture.

Animals

Central brainstem projections of the superior vagal ganglion of the cat.

The central projections of the cat superior vagal (jugular) ganglion (SVG) cells were determined using anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). WGA-HRP was injected into the SVG of 5 cats, 3 of which had the vagal nerve sectioned distal to the jugular ganglion several days previously. Following 72 h, the animals were sacrificed and the brainstem and rostral cervical spinal cord sectioned and processed with tetramethylbenzidine (TMB) and examined for anterograde transport. The vagal root afferent fibers entered the brainstem at the level of the caudal facial motor nucleus and bifurcated into descending tracts. Terminal label was identified in: the dorsal lateral subnucleus of the nucleus tractus solitarius (NTS); nucleus interpolaris and nucleus caudalis of spinal V; the ventrolateral aspect of the cuneate nucleus and; the superficial laminae (I, II) of the rostral C1-dorsal horn. To our knowledge this is the first report describing central vagal afferent terminations following injection of current axonal tract tracing substances into the isolated superior vagal ganglion. The projection of jugular ganglion cells to a region of the NTS associated with cardiovascular function is of particular interest, and may be related to ganglion cells known to innervate the cerebral vasculature and meninges.

Animals

Synovial cyst of the cervical spine.

A case of acute posttraumatic myelopathy resulting from hemorrhage into synovial cysts bilaterally at the C-6, C-7 facet joints is presented. The pathogenesis of synovial cysts remains unclear, although reports in the literature have implicated trauma leading to cyst enlargement. Hemorrhage into the cavity of the synovial cysts resulted in epidural compression of the spinal cord in this patient. Because spinal synovial cysts cannot be unequivocally diagnosed preoperatively, other more common conditions must be considered in the differential diagnosis. Radiographic analysis including plain films, computed axial tomography, and metrizamide myelography are of value in establishing a neurological diagnosis. Surgical decompression and excision of the lesion may result in significant neurological improvement.

Hemorrhage

Projections of cervical nerves to the rat medulla.

The central course of dorsal root ganglia (DRG) fibers from C1, C2 and C3, and particularly, their brainstem terminations were studied in rats using anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). WGA-HRP was injected into the exposed DRG, and after 3 days the animals were sacrificed and sections of spinal cord and brainstem were processed with tetramethylbenzidine and examined for anterograde transport. Labeled fiber terminals were identified in the dorsal horn and the central cervical nucleus in the spinal cord, and in the intermediate nucleus, cuneate nucleus, external cuneate nucleus and the caudal portion of the nucleus of the solitary tract (NTS) in the brainstem. The projection of primary sensory fibers to the visceral NTS is suggestive of a functional relationship between upper cervical and vagal nerve afferents. The potential association of these nerves with clinical problems of headache and other cephalgias is of interest.

Afferent Pathways