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Biomedical subjects

J J Gilbert

Publications and source records attributed to J J Gilbert.

At least 19 recordsLinked to original sources
PubMed1998

Antagonistic roles for phospholipase D activities in B cell signaling: while the antigen receptors transduce mitogenic signals via a novel phospholipase D activity, phosphatidylcholine-phospholipase D mediates antiproliferative signals.

Cross-linking of the Ag receptors on B cells induces DNA synthesis and proliferation. Butanol trap experiments suggest that one or more phospholipase D activities play a key role in this process. Although phosphatidylcholine-phospholipase D has been shown to play a central role in the transduction of proliferative responses for a wide variety of calcium-mobilizing receptors, we show that the Ag receptors are not coupled to this phospholipase. In addition, phosphatidylcholine-phospholipase D is not stimulated under conditions that mimic T cell-dependent B cell activation. In contrast, ATP, which inhibits surface Ig (sIg)-mediated DNA synthesis in murine B cells via P2-purinoceptors, activates phosphatidylcholine-phospholipase D. Phosphatidylcholine-phospholipase D is therefore associated with antiproliferative signal transduction in mature B cells, but it does not transduce early signals associated with sIg-mediated growth arrest or apoptosis in immature B cells. Mitogenic stimulation of sIg is, however, coupled to a novel nonphosphatidylcholine-hydrolyzing phospholipase D activity. The resultant sIg-generated phosphatidic acid, unlike the phosphatidylcholine-derived phosphatidic acid generated via the purinoceptors, is converted to diacylglycerol. These data provide the first evidence that while the novel sIg-coupled phospholipase D and resultant diacylglycerol generation may play a role in B cell survival and proliferation, phosphatidylcholine-phospholipase D may transduce, via phosphatidic acid, negative immunomodulatory signals in mature B lymphocytes.

1-Butanol↗
PubMed1996

Antigen receptors on immature, but not mature, B and T cells are coupled to cytosolic phospholipase A2 activation: expression and activation of cytosolic phospholipase A2 correlate with lymphocyte maturation.

The Ag receptors on mature B and T cells are not coupled to the activation of cytosolic phospholipase A2 (cPLA2) and arachidonic acid release. Moreover, phorbol esters such as PMA, which can activate cPLA2 via mitogen-activated protein (MAP) kinase in most cell types, also failed to induce the release of arachidonate from mature cells, suggesting that the cPLA2 pathway may not be functional in mature lymphocytes. Interestingly, Western blot analysis revealed that cPLA2, which had previously been thought to be expressed ubiquitously, is not expressed in mature B or T cells and that cytosolic phospholipase A2 expression could not be up-regulated in lymphocytes following culture with a range of cytokines most likely to be involved in an immune response such as IL-1 alpha, IL-3, or TNF-alpha. In contrast, cPLA2 was shown to be expressed and activated in thymocytes and immature B cells under conditions in which ligation of the Ag receptors led to growth arrest and/or apoptosis. Taken together, these data suggest that cPLA2 does not play a role in Ag receptor-mediated lymphocyte activation, but may be involved in the molecular mechanisms underlying lymphocyte maturation and/or self tolerance by clonal deletion.

Animals↗
PubMed1994

Nerve biopsy findings in Niemann-Pick type II (NPC)

The severe infantile form of Niemann-Pick disease type II was diagnosed in a 4-year-old girl and confirmed by demonstrating in cultured skin fibroblasts a deficiency of low-density lipoprotein-stimulated cholesterol ester synthesis of < 5% of normal. Electrodiagnostic studies revealed changes of a predominantly demyelinating motor and sensory polyneuropathy. Light microscope and ultrastructural examination of a peroneal nerve biopsy showed unique changes. Compacted myelin sheaths were disproportionately thin with marked globular irregularities in single teased nerve fibres and evidence of chronic demyelination. The majority of axons were preserved but axonal spheroids and cytoskeletal abnormalities akin to neuroaxonal dystrophy were noted. Membrane-bound multi-lobulated lysosomal inclusions of floccular and electron-dense material were present in Schwann cells (SC), endoneurial fibroblasts, macrophages, pericytes and endothelial cells. SC of myelinated fibres were stuffed with whorls of concentric osmiophilic membraneous profiles and electron-lucent material. The findings are diagnostic and differ from those of classical Niemann-Pick disease.

Axons↗
PubMed1993

Primary cerebral fibrosarcomas. Clinicopathologic study and review of the literature.

BACKGROUND: Primary of the brain and meninges are uncommon tumors. Information regarding optimum treatment is limited due to their rarity, and the best form of therapy is not yet known. METHODS: Nine patients between the ages of 22 and 61 years with primary fibrosarcomas confined to the brain and meninges were studied clinicopathologically. Tumors were superficially located in five patients and intracerebrally or deep in four patients. Treatment consisted of maximum feasible surgical resection (seven patients, gross total; one, subtotal; one, no surgery before death) and radiation therapy (45-60 Gy conventional fractionation) in eight of nine patients. RESULTS: Fibrosarcomas were moderate or high grade in seven of nine patients (78%). Immunohistochemical reactions with antisera to glial fibrillary acid protein (GFAP), cytokeratin, vimentin, desmin, and S-100 demonstrated vimentin positivity in five of nine patients and cytokeratin positivity in two of nine patients. Individual GFAP-positive cells were seen in two cases, thought to represent trapped reactive astrocytes. None were S-100-positive or desmin-positive. Eight patients have died, with a median survival time of 7.5 months (range, 1 day-96 months). Local recurrence developed in eight patients and distant recurrence in six patients. Systemic metastases developed in four patients (50%) and meningeal seeding in four patients (50%). Longer survival was observed in superficially located tumors (range, 7.5 months-96 months) compared with intracerebral tumors (range, 1 day-9 months). CONCLUSIONS: Primary fibrosarcomas of the brain are uncommon tumors, usually of high histologic grade, with a high rate of local recurrence. Their propensity for meningeal and distant relapse distinguishes them from tumors of glial origin. Immunohistochemistry is of limited diagnostic value, although it may facilitate exclusion of other diagnoses. Because the prognosis after conventional surgery with 50-60 Gy external beam radiation therapy is relatively poor, the authors recommend more aggressive therapy with maximal feasible resection followed by external beam radiation therapy to doses of 64-66 Gy. When effective chemotherapy is established for soft tissue sarcomas of the extremities, this should be evaluated in view of the high incidence of distant metastases.

Adult↗
PubMed1993

Severe axonal degeneration in acute Guillain-Barré syndrome: evidence of two different mechanisms?

Four cases of severe acute Guillain-Barré syndrome (GBS) characterized by severe axonal degeneration are presented. All had electrically inexcitable motor nerves as early as 4 days after onset. The disease was rapid in onset and the residual disability was severe. Two different types of pathology were seen. Nerve biopsies in 3 cases showed severe axonal degeneration without inflammation or demyelination. Autopsy in one of these cases showed that the dorsal and ventral roots were also significantly affected. These cases illustrate the primary axonal form of GBS. Nerve biopsy in the fourth case at day 15 showed marked inflammation and demyelination with axonal degeneration. Contralateral nerve biopsy at day 75 showed almost complete loss of axons. This case illustrates another type of axonal degeneration, that which occurs secondary to inflammation and demyelination.

Aged↗
PubMed1992

Effect of anti-interferon-gamma and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse.

SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-interferon-gamma (IFN-gamma) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-gamma to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-gamma. These findings support the notion that IL-2 is required for disease induction whereas IFN-gamma plays a disease-limiting role early in the development of EAE.

Animals↗
PubMed1991

Cysts of the neuraxis of endodermal origin.

Five colloid cysts of the third ventricle were compared with two spinal enterogenous cysts to examine the hypothesis that these entities have the same origin from primitive endodermal tissue. All the lesions showed cuboidal and columnar epithelium with mucus containing goblet cells and cilia. Immunohistochemistry for cytokeratin, EMA and CEA was positive in all the colloid cyst and enterogenous cyst epithelium. S-100 was focally positive in three of the colloid and one of the enterogenous cysts while vimentin and GFAP were negative in both. The anatomical distribution of both colloid and enterogenous cysts is reviewed. An illustrative case of an identical cyst within the fourth ventricle is presented. This suggests that the similarities between colloid and enterogenous cysts and the presence of identical lesions along the neuroaxis indicate that these structures are derived from primitive foregut endoderm.

Adult↗
PubMed1990

NMR studies in experimental allergic encephalomyelitis: factors which contribute to T1 and T2 values.

To determine the factors which may alter NMR relaxation times in multiple sclerosis (MS) lesions we measured the proton T1 and T2, specific gravity (SG), and histology in the central nervous system (CNS; 13-19 levels per animal) in the myelin basic protein (MBP) and CNS-induced acute and relapsing EAE models in 44 juvenile Hartley guinea pigs. In the MBP model, T1 is unchanged but T2 is prolonged before symptoms and pathological changes occur. T2 remains prolonged during the acute phase of MBP-induced EAE. In the acute CNS model, T1 and T2 were not different from control despite advanced pathological changes of inflammation and demyelination and changes in specific gravity, indicating a marked change in tissue water content. No single variable, pathological or SG, could predict T1 or T2 values in the CNS-induced model. In active disease in the MBP model, when edema occurs in the presence or absence of parenchymal infiltration, T2 values are increased. However, as the factors which influence tissue NMR characteristics are complex in these MS models, it is likely difficult to infer specific pathological events from MRI findings in patients with MS.

Acute Disease↗
PubMed1990

Treatment of spinal cord-induced experimental allergic encephalomyelitis in the Lewis rat with liposomes presenting central nervous system antigens.

Chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) in the Lewis rat, induced by the injection of spinal cord tissue in complete Freund's adjuvant (SC/CFA), was studied in vivo by treatment with liposomes containing central nervous tissue antigens, and in vitro by lymphocyte proliferation assays. Intracardiac administration of myelin basic protein (MBP) liposomes, galactocerebroside (GC) liposomes, or MBP + GC liposomes substantially reduced the clinical severity and/or delayed the onset of the initial phase of disease. Liposomes prepared from whole myelin provided even greater protection, and were effective at suppressing both the first disease episode and the relapses. These results indicate that while GC and MBP may play significant roles in the development of CR-EAE in the Lewis rat, immune responses to other antigens are probably also involved. Splenic and lymph node lymphocytes from MBP-GC liposome-treated rats, and splenic lymphocytes from cytochrome-GC (CYT-GC) liposome-treated rats, showed drastically reduced abilities to proliferate in response to MBP in culture. Spleen cells from both the MBP-GC- and CYT-GC-liposome-treated donors were able to actively suppress antigen-induced proliferation of MBP-primed lymphocytes. These findings suggest participation of both clonal anergy, and active suppressor cells in the liposome-mediated suppression of CR-EAE in the Lewis rat.

Animals↗
PubMed1990

Some clinical and pathologic observations on chronic myelopathy: a variant of multiple sclerosis.

Four patients with progressive demyelinating myelopathy with symptoms spanning six to 25 years are described. There was no clinical evidence of dissemination of lesions in the central nervous system. Radiological evidence of dissemination was present in two cases; in one this was absent at the time of presentation and was only demonstrated after six years of progressive unifocal disease. In one case, pathological examination revealed a solitary area of chronic demyelination. In all cases but one, oligoclonal bands were detected on cerebrospinal fluid (CSF) electrophoresis. Some cases of chronically progressive myelopathy result from focal demyelination in the absence of a second lesion demonstrable by clinical, radiographic or necropsy examination.

Aged↗
PubMed1990

The significance of myoclonic status epilepticus in postanoxic coma.

We report 11 adults who exhibited myoclonic status epilepticus (MSE) after cardiac arrest. Based on pathologic, electroencephalographic, and clinical evidence, we conclude that our patients died from the initial anoxic-ischemic insult rather than as a result of MSE. We suggest that the seizures in these nonsurvivors were self-limited events arising from lethal damage to neurons. Thus, in patients with bilaterally synchronous facial myoclonus, bilateral loss of pupillary or oculovestibular reflexes, and suppression and burst-suppression on EEG, it is not warranted to use anesthetic barbiturates to treat MSE.

Adult↗
PubMed1989

Chronic-relapsing experimental allergic encephalomyelitis in strain-13 guinea pigs: cell-mediated immunity and IgG isoelectric focusing in myelin basic protein-liposome-treated and untreated animals.

Juvenile strain-13 guinea pigs challenged with whole central nervous system (CNS) tissue in complete Freund's adjuvant (CFA) developed chronic-relapsing (CR) experimental allergic encephalomyelitis (EAE). The animals that recovered from the first clinical episode were divided into three groups. One group was left untreated, one group was treated with three intracardiac injections of 100 micrograms glutaraldehyde-fixed myelin basic protein (MBP)-liposomes (MBP-L-GA) given once a week, and one group was treated with cytochrome c-liposomes (CYC-L-GA). The animals treated with MBP-liposomes were very well protected against further relapses. In vitro proliferative responses of peripheral blood lymphocytes (PBL) were performed repeatedly on most animals. The lymphocytes exhibited excellent proliferative responses to MBP, proteolipid apoprotein (PLP) and whole myelin, as well as to purified protein derivative (PPD) and concanavalin-A (ConA). High proliferative responses were recorded over the entire period of observation which lasted 12-22 months, each time the animals were tested in remission or in full relapse. However, a sharp decrease in proliferative responses was observed in most animals when the assay was performed 24-48 h before to 24 h after entering a relapse. The results demonstrate the presence of long-term and sustained cell-mediated responses to two distinct neuroantigens, and show fluctuations of both neuroantigen-specific and nonspecific responses concordant with a well-defined phase of the disease. Isoelectric focusing and immunofixation was performed on sera and cerebrospinal fluids obtained at the time of sacrifice. The pattern showed clear oligoclonal IgG bands (OB) in the samples obtained from untreated, CYC-L-GA-treated as well as in the MBP-L-GA-treated animals.

Animals↗
PubMed1989

Jugular venous bulb catheterization in infants and children.

Cross-brain oxygen extraction may be altered by coma, hyperventilation, hypothermia, or barbiturates, and has been demonstrated in adults and more recently in children to be related to functional neurologic recovery after a variety of brain injuries. However, measurement of cross-brain oxygen extraction in children is currently not a part of routine clinical care, partly because there have been no published attempts relating the technique of jugular venous bulb (JVB) catheterization and its complication in children. We catheterized the JVB to measure cerebral venous oxygen content and calculate cross-brain oxygen extraction in 26 deeply comatose neonates and children ranging in age from a few hours to 14 yr. Bedside catheterization using the Seldinger technique was successful in 25 children, with standard venous cutdown necessary in the remaining child. All JVB catheterizations were performed with parental consent and during continuous monitoring of the intracranial (ICP) or fontanelle, as well as arterial, pressure. ICP was not significantly altered by the cannulation procedure in any of the children studied, although the cannulation occurred early in the child's course when ICP was well controlled. Inadvertent carotid artery puncture with bleeding controlled by local pressure occurred in four children, and catheter malposition was confirmed on lateral skull xray in two others. Jugular venous bulb catheters remained in place for 2 to 7 days (average 3) and malfunction or obstruction of the catheter did not occur. Organisms were grown from three of 26 catheter tips submitted for culture, with peripheral blood cultures also positive for the same organisms in two of these.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Metastatic anaplastic oligodendroglioma.

We report 7 patients, ages 21 to 49 years, with systemic metastasis from anaplastic oligodendroglioma. Metastases developed in the scalp, cervical lymph nodes, bone, and other organs 1 to 76 months after the most recent surgery and 18 to 86 months after diagnosis. Systemic metastases responded to focal radiotherapy or nitrosourea-based chemotherapy for 6 to 18 months. Five patients have died, 4 to 24 months after the appearance of systemic metastases, all with progressive cerebral and systemic tumor. We observed 2 distinct patterns of spread of oligodendroglioma. Pattern 1, initial scalp or regional lymph node involvement followed by distant metastasis, was associated with multiple craniotomies. Pattern 2, distant metastasis without scalp or regional lymph node spread, was associated with early radiotherapy and chemotherapy. Longer-than-expected survival was not essential to metastasis. We speculate that anaplastic oligodendrogliomas possess special characteristics favoring metastasis and that early aggressive treatment alters the biology of this disease.

Adult↗
PubMed1988

Effect of treatment with glutaraldehyde-fixed myelin basic protein-liposomes on active induction and passive transfer of experimental allergic encephalomyelitis in Lewis rats.

Guinea pig myelin basic protein (MBP)-liposomes were prepared and fixed with 0.2% glutaraldehyde (GA). Lewis rats were treated with glutaraldehyde-fixed MBP-liposomes (MBP-L-GA) or with cytochrome-c-liposomes (CYC-L-GA), 7 days before and 7 days after challenge with MBP in CFA. Rats treated with MBP-L-GA, but not with CYC-L-GA, were very well protected against the clinical manifestations of EAE. The protection was better than that obtained after treatment with conventional MBP-liposomes (without glutaraldehyde). Furthermore, when grown in vitro for 72 hr in the presence of MBP, lymphocytes from rats treated with MBP-L-GA and challenged with MBP in CFA exhibited a marked decrease in their ability to transfer EAE to normal syngeneic recipients.

Animals↗
PubMed1988

Dementia, parkinsonism, and motor neuron disease: neurochemical and neuropathological correlates.

The neurochemical markers for the major neurotransmitter systems were measured in the brain of a patient who died with a dementia-parkinsonism-motor neuron disease (DPMN) syndrome complex. Moderate neuronal loss in the substantia nigra, spongiform changes in the frontal cortex, and moderate anterior horn cell loss throughout the spinal cord were observed. A severe nigrostriatal dopamine deficiency provides the basis for the observed parkinsonian features. The dementia is unexplained.

Caudate Nucleus↗