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Biomedical subjects

D A Kristt

Publications and source records attributed to D A Kristt.

At least 19 recordsLinked to original sources
PubMed1996

Differences between phosphotyrosine accumulation and Neu/ErbB-2 receptor expression in astrocytic proliferative processes. Implications for glial oncogenesis.

BACKGROUND: Previous work has shown that enhanced growth potential of malignant astrocytomas correlates with increased expression of growth factor receptor tyrosine kinases. The functional implications of increased receptor expression were addressed by analyzing possible accumulation of phosphotyrosyl proteins in neoplastic and nonneoplastic astrocytic proliferative processes. The results were compared with the expression of Neu receptor protein (also called ErbB-2 or HER-2). METHODS: Western immunoblots and immunocytochemistry were utilized to evaluate glioma and carcinoma cell lines, neonatal astrocytic cultures, and human brain biopsies of graded gliosis and astrocytomas. The effects of three tyrosine kinase inhibitors on 3H-thymidine uptake and cell proliferation and viability were examined in cultured glioma cells. RESULTS: Phosphotyrosine was conspicuously elevated in all three grades of astrocytoma, but remained at low levels in nonneoplastic astrocytic proliferations. Dose-dependent decreases in DNA synthesis and proliferation of cultured glioma cells occurred after inhibition of tyrosine kinase. Neu receptor protein showed increased expression in malignant astrocytomas (including glioblastomas) and severe reactive gliosis. CONCLUSIONS: Upregulation of tyrosyl protein phosphorylation enables differentiation of neoplastic from nonneoplastic astrocytic proliferative states. Inhibition of this phosphorylation impairs growth of cells. Increased Neu receptor protein expression can distinguish malignant from low grade astrocytomas. We speculate that genetic events leading to stably increased phosphotyrosine may be critical for neoplastic transformation of astrocytes, whereas increased receptor tyrosine kinase expression could be a factor in the aggressive growth associated with malignancy.

Adolescent↗
PubMed1996

Pathologic evaluation of fresh tissue from neurosurgical biopsies: technical and interpretational aspects.

A number of rapid techniques are available for intraoperative consultations on neurosurgical biopsies. The press preparation, introduced in this report, is a less traumatizing variation of smash/smear/crush techniques for fresh tissue. It can be prepared in less than 5 min. The purpose of the present report is to describe the technique and its key applications. An additional goal of this study was to identify novel differential diagnostic possibilities that may arise in these preparations. It was found that press preparations clearly maintain the tissues' cytologic features, while key histologic components are preserved in larger fragments. To exemplify the findings using this approach, the features of astrocytomas are described. It is concluded that the press preparation is a rapid and informative means to facilitate pathologic evaluation of fresh tissue from neurosurgical biopsies.

Astrocytoma↗
PubMed1995

Radiologic appearance of the dysembryoplastic neuroepithelial tumor.

PURPOSE: To evaluate the computed tomographic (CT) and magnetic resonance (MR) imaging features of dysembryoplastic neuroepithelial tumor (DNT). MATERIALS AND METHODS: Six CT studies (four with contrast material enhancement) and 10 MR imaging studies (seven with gadolinium enhancement) obtained in 10 patients with a history of seizures and pathologically proved DNT were retrospectively reviewed. RESULTS: All tumors were intracortical or subcortical. CT showed a low-attenuation mass in all cases except one of mixed isoattenuation and low attenuation. The DNT had decreased signal intensity on T1-weighted MR images and well-demarcated increased signal intensity on T2-weighted images without peritumoral edema. Prominent MR imaging features were a gyriform configuration on T1- or T2-weighted images in 10 patients (100%), well-demarcated lobular tumor margins on T2-weighted images in eight (80%), and a high rate of bone remodeling of the adjacent calvaria on MR (60% [n = 6]) and CT (67% [n = 4]) images. CONCLUSION: Diagnosis of DNT with imaging modalities alone may be difficult, but these radiologic features may aid in differentiating DNT from other gliomas.

Adolescent↗
PubMed1995

Posterior fossa glioblastoma multiforme: MR findings.

PURPOSE: To characterize the MR findings of glioblastoma multiforme in the posterior fossa. METHODS: MR studies of nine patients with surgically proved posterior fossa glioblastoma multiforme were retrospectively evaluated. MR characteristics studied included tumor location, signal intensity, enhancement pattern, and presence of intratumoral hemorrhage, as well as presence of secondary hydrocephalus or metastatic spread. RESULTS: The tumors were located in the median portion of the cerebellum or brain stem in eight cases. Six extended into the fourth ventricle. Hydrocephalus was seen in four cases. Six cases demonstrated decreased T1- and increased T2-weighted signal intensities. Three cases demonstrated mixed signal intensities suggesting intratumoral hemorrhage. All of the eight patients who received contrast showed moderate to marked heterogeneous ringlike enhancement suggesting intratumoral necrosis. Multicentric/multifocal lesions or extraaxial metastases were identified in three of the nine cases, and there was extracranial extension into the cervical region in one case. CONCLUSION: Glioblastoma multiforme is a rare tumor in the posterior fossa. Differentiating it from metastatic tumor or malignant astrocytoma was difficult. However, combination of heterogeneous and ringlike enhancement, midline location, poorly defined margin, tumoral hemorrhage, concomitant multicentric/multifocal lesions, and extraaxial or extracranial metastasis may be clues for the prospective diagnosis of glioblastoma multiforme.

Adult↗
PubMed1994

Melanoma arising in a cervical spinal nerve root: report of a case with a benign course and malignant features.

A 20-year-old caucasian woman with a 5-year history of right arm, neck, and back pain sought treatment when an automobile accident (4 months before admission) exacerbated her pain. Magnetic resonance imaging revealed an intra- and extradural mass compressing the spinal cord at the C5-C6 level. It also extended into and widened the neural foramen, mimicking a neurofibroma. A single cafe-au-lait spot was discovered in the inguinal region. A two-staged surgical resection was performed on an apparent hemorrhagic C6 nerve root mass. The mass exhibited diagnostic features of a malignant melanoma histologically, immunocytochemically, and ultrastructurally. A search for a primary lesion outside the nervous system or other metastases during an 8-year period from the onset of symptoms has been negative. The patient's chronic history, evidence of neural foraminal enlargement, and the absence of other malignant melanoma lesions or subsequent metastases indicates that this lesion may be a primary melanoma of the nerve root with a benign course.

Adult↗
PubMed1994

Fourth ventricular hemangioblastoma associated with pheochromocytoma and renal medullary fibroma.

Intraventricular hemangioblastomas are exceptionally rare. Of the cases described in the literature, very few were associated with von Hippel-Lindau disease. We present a highly unusual case of a fourth ventricular hemangioblastoma associated with a pheochromocytoma and a renal medullary fibroma. This may represent a forme fruste of the von Hippel-Lindau complex. A workup for papilledema resulted in the discovery of this rare finding.

Adrenal Gland Neoplasms↗
PubMed1993

Receptor tyrosine kinase expression in astrocytic lesions: similar features in gliosis and glioma.

The purpose of this study was to determine if the expression of receptor tyrosine kinases would distinguish astrocytosis from astrocytoma. Because the expression of this family of receptor proteins is greater in higher-grade tumors, a graded series of both reactive and neoplastic astrocytic lesions in humans was evaluated. The reactive processes included both mild gliosis and severe (intense) gliosis. The two immunocytochemically detected membrane receptor proteins, p145 and p185, are those encoded by the kit and neu genes, respectively. Semi-quantitative assessments were made independently for the frequency and intensity of astrocytic immunostaining together with corollary immunocytochemical staining to detect glial fibrillary acidic protein. It was found that both mild gliosis and low-grade astrocytomas only minimally express these receptors. In contrast, severe gliosis and high-grade neoplasms consistently express these receptors at much higher levels. In both astrocytosis and astrocytomas, a cell with abundant perikaryal cytoplasm is most likely to be immunoreactive, often with dense reaction product concentrated at the periphery of the somal cytoplasm. The extent and pattern of immunoreactivity in high-grade astrocytomas preclude the interpretation that all immunoreactive cells were merely reactive astrocytes. We conclude that the expression of these receptors per se does not differentiate astrocytic neoplasia from reactive astrocytosis. Second, we conclude that immunocytochemically detectable levels of neu or kit receptor expression is not constitutive in normal astrocytes and in some stages of astrocytic neoplasia. On the basis of these findings, we speculate that some neoplastic astrocytes maintain and manifest the capacity to respond to transitory exogenous stimuli, as do reactive astrocytes. This reaction could include the elaboration of receptor tyrosine kinases. Alternatively, even if the function of these receptors in gliosis differs from that in gliomas, the common expression could still reflect an "active" state shared by astrocytes in these two processes.

Adolescent↗
PubMed1991

Penetration and internalization of plasma proteins in the human spinal cord.

In animal studies, motoneurons take up plasma proteins including immunoglobulins at their terminals. These proteins are then transported back to cell bodies in the spinal cord. To determine if these processes also occur in humans, we localized several different plasma proteins in autopsied spinal cords from 13 patients without neurological disease. As in animals, plasma proteins are associated with vascular and pial structures. Motoneurons, particularly large cervical and lumbar motoneurons, frequently showed immunoreactivity within their cytoplasm to several plasma proteins. Motoneuron labeling was more consistent with antisera against plasma proteins of lower molecular weights such as IgG, IgA and transferrin, than with antisera against higher molecular weight proteins such as IgM and alpha-2-macroglobulin. Other large neurons without connections outside the blood-brain barrier such as those of Clarke's column also occasionally labeled with antisera against all plasma proteins tested. Our results are compatible with the concept that motoneurons take up and transport plasma proteins. These neurons can be distinguished from cells which internalized extravasated serum proteins before and after death. Uptake of pathogenic antibodies by motoneuron terminals may play a role in the pathogenesis of motoneuron disease.

Adult↗
PubMed1991

Organization and development of the cingulum: laminar arrangement of acetylcholinesterase-rich components in rat.

The cingulum of the rat is seen to be composed of several distinct fiber and neuronal somal components. In histochemical preparations, three acetylcholinesterase (AChE)-rich fiber zones are noted. The most dorsal originates in the cholinergic cell groups of the basal forebrain, (BF). There is a second, poorly reactive region subjacent to the BF afferent zone. The third, and most ventral zone, has not been described previously. It is operationally dubbed the entocingular fasciculus, ECF. It consists of a moderately dense plexus of AChE-reactive axons and dendrites. In contrast to the regularity and coherence of BF afferents, ECF fibers run in all directions in relation to adjacent cortical (cingulate, sensory-motor), subcortical and transcallosal sites. Knife cut lesions indicate the presence of a substantial proportion of fibers that travel either rostrally or caudally within the ECF itself. The small number of neuronal somata within the cingulum are mostly localized to the ECF. Ultrastructurally, these cells appear to synthesize AChE and form a single type of axo-somatic synapse; synapses are not common in the ECF. Altogether, these observations suggest that the ECF is a conduit for AChE-rich fibers directed towards targets outside of this structure. The AChE reactivity within the ECF first becomes apparent in the second postnatal week, lagging somewhat behind the enzymological maturation of BF afferents. It is concluded that in addition to BF afferents, other AChE-rich fibers travel in the cingulum. A distinctive population of fibers appears to bridge between various cerebral sites via the ECF. These latter observations raise the speculative possibility of a role for the ECF in limbic and sensorimotor cortical interactions.

Acetylcholinesterase↗
PubMed1991

Myelopathic neurosarcoidosis: diagnostic value of enhanced MRI.

Neurosarcoidosis is an underdiagnosed variant of the systemic disease. We report a case of myelopathic neurosarcoidosis, noting the contribution made by MRI in establishing the diagnosis, and we discuss the possibility that the disease is differentially responsive to various steroid formulations.

Adult↗
PubMed1990

Internalization of plasma proteins by cerebellar Purkinje cells.

Animal studies suggest that Purkinje cells internalize proteins from the blood and CSF. This process may relate to the pathogenesis of paraneoplastic cerebellar degeneration in patients with anti-Purkinje cell antibodies. To determine if human Purkinje cells may also internalize plasma proteins, cerebellar tissue was taken from routine autopsies of eight patients without neurologic or neoplastic disease. Several plasma proteins including IgG, IgA, IgM, transferrin, albumin and alpha-2-macroglobulin were detected by immunohistochemistry within the cytoplasm of Purkinje cells. Internalized proteins frequently filled the entire soma and major dendrites, sparing the nucleus. Vascular structures were also immunolabeled, while glia internalized plasma proteins differentially, with oligodendrocytes selectively internalizing transferrin. Purkinje cells were the most numerous and heavily labeled neuronal cell type in spite of their small numerical representation in the cerebellar neuronal population. Our results are compatible with previous animal studies, and suggest that internalization of specific antibodies could contribute to the pathogenesis of Purkinje cell loss in paraneoplastic cerebellar degeneration.

Aged↗
PubMed1989

Acetylcholinesterase in immature thalamic neurons: relation to afferentation, development, regulation and cellular distribution.

The transient appearance of intense acetylcholinesterase reactivity in some immature, noncholinergic neurons has not been adequately explained. In this study two questions were investigated that relate to several possible roles for acetylcholinesterase. First, what factors influence the onset and maintenance of reactivity? Second, what are the temporal and spatial features of the cellular expression in relation to stages of neuronal development? Using light- and electron-microscopic histochemical methods, the non-cholinergic ventrobasal complex in thalamus of the immature rat was examined. Ultrastructural observations on fetal ventrobasal complex demonstrated that the onset of acetylcholinesterase reactivity precedes ingrowth of most extrinsic afferents. These inputs are, therefore, unlikely to provide the signal for onset. In transplants and explants, acetylcholinesterase persisted in ventrobasal complex neurons independent of their principal afferents. However, afferentation can affect reactivity. The patterned variation in intensity, characteristic of infant ventrobasal complex, was dramatically altered by unilateral interruption of its afferentation. The changes in intensity patterning could reflect changes in acetylcholinesterase metabolism, since postnatal treatment with an irreversible inhibitor (diisofluorophosphate) in vivo demonstrated resynthesis of acetylcholinesterase. The period of peak intensity of acetylcholinesterase reactivity normally began abruptly at 18 days of gestation +/- 12 h and continued until 4-6 days postnatally. This period follows neurogenesis and migration, but precedes active synaptogenesis. It coincides with outgrowth and initial contacting of cell processes in the ventrobasal complex. The timing complements the ultrastructural finding that acetylcholinesterase-dependent reaction product most commonly is localized to small patches of surface membrane, where distal processes contact each other, non-synaptically. Together these data suggest three points. First, that the expression of acetylcholinesterase in the immature ventrobasal complex neuron is probably under active metabolic control, responsive to both intrinsic and environmental factors. Second, that acetylcholinesterase expression is unlikely to result from a transient cholinergic input. Third, that the temporal and spatial characteristics of histochemical reactivity enable exclusion of several previously suggested explanations for the occurrence of acetylcholinesterase in the ventrobasal complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
PubMed1989

Inhibition of amino acid transport and protein synthesis by HgCl2 and methylmercury in astrocytes: selectivity and reversibility.

The previously reported observation that submicromolar concentrations of HgCl2 inhibit glutamate uptake reversibly in astrocytes, without effect on 2-deoxyglucose uptake, suggested that elemental mercury vapor, which is oxidized to mercuric mercury in the brain, might cause neurodegenerative change through the mediation of glutamate excitotoxicity. Here, selectivity is explored further by measuring the inhibition of other amino acid transporters and protein synthesis as a function of HgCl2 concentration. The properties of MeHgCl were compared under identical conditions, and some morphological correlates of function were examined. Inhibition of amino acid transport by HgCl2 was selective, whereas MeHgCl was nonselective. The 50% inhibitory concentrations of HgCl2 for uptake of alpha-aminoisobutyric acid by system A, uptake of alpha-aminoisobutyric acid or kynurenine by a system L variant, and uptake of gamma-aminobutyric acid were all two- to fourfold greater than that for uptake of glutamate. The submicromolar concentrations of HgCl2 that inhibited glutamate transport also inhibited protein synthesis, but in a rapidly reversible fashion, and elicited only discrete ultrastructural changes (heterochromatin, increased numbers of lysosomal bodies, and increased complexity of cell surface). In contrast, inhibition of protein synthesis by MeHgCl was acutely (1-h) irreversible and became marked only at concentrations higher than those that elicited gross morphologic change in the form of "bleb"-like swellings. The results lend support to the proposed excitotoxic mediation of mercury vapor neurotoxicity and reveal a sharp contrast between the effects of HgCl2 and MeHgCl on astrocytes.

Amino Acids↗
PubMed1989

Pituitary hyposecretion and hypersecretion produced by a Rathke's cleft cyst presenting as a noncystic hypothalamic mass.

A 53-year-old man presented with polydipsia, polyuria, lightheadedness on standing, and syncope. Visual field deficits suggesting left optic tract compression and pituitary dysfunction consisting of diabetes insipidus, hyperprolactinemia, and anterior pituitary insufficiency were diagnosed. On the computed tomography scan, an isodense, ring-enhancing, parasellar mass was localized primarily in the suprasellar region and also extended into the sella. It was believed that the pituitary hormone hypersecretion and hyposecretion were due to hypothalamic dysfunction from the mass which was initially believed to be a craniopharyngioma. At surgery a Rathke's cleft cyst was resected. The unusual presentation of this Rathke's cleft cyst presenting as a hypothalamic lesion is discussed.

Craniopharyngioma↗
PubMed1987

Morphological responses to local CNS trauma: sprouting and synaptogenesis within membranes implanted into mature cerebral cortex of the rat.

The purpose of this study was to document in vivo neuronal sprouting in response to local trauma of the mature cerebral neocortex. The experimental approach enabled direct and unequivocal ultrastructural identification of newly sprouted neuronal processes and their synaptic relationships. Morphologically detectable factors that influence neuronal sprouting were also assessed. Tiny fragments of porous, synthetic membrane were implanted into the mature neocortex of the rat. After one week, axons, dendrites, growth cone-like structures, synapses, and processes from astrocytes and microglia were present deep within the interstices of the implant. Morphometric analysis of synapses within the implant, support the qualitative impression of active neuronal ingrowth and de novo synaptogenesis by these sprouted elements. Astrocytic processes appear to comprise the major barrier to neuronal invasion of the implant. Several observations suggested that glia sometimes may facilitate neuronal ingrowth. These findings provide direct morphological documentation of axonal and dendritic plasticity in the mature rat neocortex. The work demonstrates a strategy that could be useful for further evaluating the cellular mechanism of in vivo neuronal regeneration.

Animals↗
PubMed1986

Late postnatal changes in rat somatosensory cortex. Temporal and spatial relationships of GABA-T and AChE histochemical reactivity.

Temporal and spatial developmental relationships between AChE and GABA-T reactivity in the sensory-motor cortex of rat were evaluated histochemically. Special attention was given to the barrels in layer IV of SmI that stain intensely for both enzymes. In the first and second postnatal weeks very low levels of diffuse GABA-T reactivity are seen in cortex, although cells and neuropil in the neostriatum are already clearly positive neonatally. There is little change until 16-18 days postnatal (dpn), when a steady increase in overall cortical reactivity for GABA-T has begun. In layer IV of SmI cortex, relatively intense foci of GABA-T staining begin to appear then, that overlap the barrel centers. GABA-T reactive non-pyramidal neurons at the periphery of these stained foci have distinctly stained processes that may enter the barrel centers. The intensity of GABA-T staining increases until 28 dpn when adult levels were reached. In contrast, AChE staining in cortex begins to appear at 2-3 dpn with prominent barrel staining seen by 6 dpn. When adult AChE reactivity levels are being achieved throughout all regions of neocortex, between 16-19 dpn, the barrel centers progressively lose demonstrable AChE-staining of their fiber plexus. Hence, the onset of GABA-T staining in the barrels during the third week postnatally coincides with the initiation of the progressive reduction in intensity of AChE staining in the same cortical zones. These observations on GABA-T correlate well with biochemical information on the time course of the maturation of the cortical GABAergic system.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobutyrate Transaminase↗
PubMed1985

Basal forebrain innervation of rodent neocortex: studies using acetylcholinesterase histochemistry, Golgi and lesion strategies.

Acetylcholinesterase (AChE)-rich projections from basal forebrain to neocortex cerebri were characterized in the present study. The purpose was to investigate 3 aspects of these projections in rats and mice that have been incompletely described in previous work: intracortical organization of the fibers, subcortical pathways and axonal branching patterns of individual basal forebrain neurons. AChE histochemistry, lesions and Golgi impregnations were the principal strategies employed in this light microscopic study. The moderately dense, AChE-stained innervation of neocortex can be altered by intracortical lesions. The results depended on the region involved and the orientation of the lesion. Sagittal knife cuts had barely detectable effects, regardless of sites. Coronal knife cut lesions in medial cortex resulted in substantial loss of staining in cingulate and medial occipital fields. In contrast, coronal lesions of lateral or anterior cortex produce only small zonal reductions in staining. The interpretation of the latter findings that we favor is that AChE-rich basal forebrain fibers enter lateral/anterior cortex and branch densely there, but in tangentially limited and overlapping terminal domains. Observations on the topography and targets of AChE-rich basal forebrain cortical afferents revealed that the fibers could be grouped based on certain characteristics. Three sets of fibers were distinguishable: anterior pathway innervating cortex of the frontal pole. These fibers were traceable to the region of the substantia innominata/nucleus basalis. They crossed the neostriatum and external capsule in the sagittal plane, forming in 3 dimensions an orderly sheet-like array of fibers bridging the anteroventral surface of the neostriatum with nearby polar cortex medial pathway innervating cingulate and medial occipital cortex. Emerging predominantly from the region of the diagonal band, the fibers run caudally as a triangular bundle in deep layer VI of cingulate cortex. lateral pathway innervating most of remaining lateral neocortex. The fibers radiate out from substantia innominata/nucleus basalis with a complex 3-dimensional organization. In all pathways, fibers enter and initially run within layer VI before ascending pialward, although the intracortical course in layer VI differs between pathways. These fibers primarily terminate in layer V with a secondary concentration in layer I. However, the latter appears to receive substantial AChE-stained inputs from other sources, possibly intracortical, as well. The pathways overlap at their respective boundary zones. This system is comparably organized in rats and mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗