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Biomedical subjects

J B Posner

Publications and source records attributed to J B Posner.

At least 91 records · Page 5Linked to original sources
PubMed1992

Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients.

We reviewed the clinical findings in 55 patients with cerebellar degeneration associated with the anti-Yo antibody (an anti-Purkinje cell antibody identified in this study by histochemistry and Western blot). The patients were all women, 26 to 85 years old. Fifty-two of them proved to have malignancies, almost exclusively breast or gynecologic cancers and usually confined to the involved organs and local lymph nodes. One woman had adenocarcinoma of the lung, and in three no malignancy has yet been identified. In 34 of 52 patients with cancer, the neurologic syndrome preceded the diagnosis of cancer and in many led to that diagnosis. Patients subacutely developed a pancerebellar disorder that was substantially disabling in most, with 37 of 48 assessable patients being unable to walk or sit unassisted. Laboratory evaluation revealed lymphocytic pleocytosis in 35 patients, with eventual cerebellar atrophy on imaging studies in seventeen. The disabling neurologic syndrome generally did not respond to treatment, but the cancer was often successfully treated. The presence of the anti-Yo antibody in patients with cerebellar symptoms warrants an aggressive approach to diagnosis and treatment of the underlying cancer, as many are curable at the time neurologic symptoms develop.

Adult↗
PubMed1992

Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin's disease.

We reviewed clinical findings and serologic data on 18 men and three women with paraneoplastic cerebellar degeneration (PCD) associated with Hodgkin's disease (HD). The patients were 20 to 77 years old (median, 44). The lymphoma preceded neurologic symptoms by 1 to 54 months in 17/21 patients, but stage or activity did not correlate with severity of neurologic disease; six developed PCD while in HD remission. PCD evolved subacutely (over weeks to months) and was pancerebellar in most. Ten had downbeat nystagmus. Thirteen stabilized in a disabled state (wheelchair- or bed-bound), five stabilized ambulatory, and three, who had progressed to a nonambulatory state, recovered. The clinical findings were usually only cerebellar but one patient had an encephalopathy, three long-tract signs, and two sensory neuropathy. Plasmapheresis (seven patients) and corticosteroids or other immunosuppressant medication (eight patients) did not help; one improved dramatically after treatment with clonazepam. Two patients improved spontaneously. Six patients had serum antibodies that reacted specifically with Purkinje cells. The pattern was distinct from that of PCD with gynecologic cancer (anti-Yo) or small-cell lung cancer (anti-Hu). Western blotting failed to identify a discrete Purkinje cell antigen. Seropositive patients did not differ clinically from their seronegative counterparts. HD-associated PCD is more common in men and in a younger age group than in PCD with other malignancies.

Adult↗
PubMed1992

Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.

Aged↗
PubMed1992

Ataxia in epidural spinal cord compression.

Nine patients presented with ataxia as the primary manifestation of epidural spinal cord compression. Eight had known cancer, the ninth an epidural abscess. Lower-extremity dysmetria, gait ataxia, or both, were the only neurologic signs in five patients. An incorrect initial diagnosis led to delay in treatment and subsequent neurologic deterioration in six patients. Failure to recognize isolated, painless ataxia as the initial manifestation of spinal cord compression and appropriately treat the disorder can result in irreversible spinal cord deterioration.

Abscess↗
PubMed1992

Vasogenic brain edema induced by arachidonic acid: role of extracellular arachidonic acid in blood-brain barrier dysfunction.

The effects of free arachidonic acid on the capillary permeability of normal rat brains were studied by measuring the regional uptake of [14C]aminoisobutyric acid by a quantitative autoradiographic technique. Intracerebral infusion of sodium arachidonate increased capillary permeability in a dose-dependent manner up to a concentration of 2 mmol/L. A high dose of arachidonic acid (more than 5 mmol/L) produced marked tissue destruction around the injection site (needle track) and increased capillary permeability less than 2 mmol/L arachidonic acid did. A time-course study demonstrated that about 80% of the maximum increase in capillary permeability produced by arachidonic acid was observed within 2 hours after the infusion was initiated. In addition, capillary permeability gradually increased with time up to 24 hours, after which it declined to about half of the maximum increase 48 hours after infusion. These effects of arachidonic acid on capillary permeability were localized within about 1.6 mm around the injection site. Pretreatment with dexamethasone did not completely, but did significantly, inhibit the arachidonic acid-induced increase in capillary permeability. The inhibitory effect of dexamethasone was completely suppressed by the administration of actinomycin D, which inhibits de novo protein synthesis, 1 hour before the treatment with dexamethasone. These results suggest that arachidonic acid, which is released and accumulated in the extracellular space, increases the capillary permeability of the brain in at least two different ways. One is the direct action of the arachidonic acid itself, which can stimulate perturbation of the membrane of the capillary endothelial cells, thus promoting an increase in capillary permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Pathogenesis of central nervous system paraneoplastic syndromes.

The pathogenesis of central nervous system paraneoplastic syndromes has not been established. Increasing evidence supports the hypothesis that CNS paraneoplastic syndromes are immune disorders arising from an immune response to the underlying neoplasm. The hypothesis is that antigens or epitopes shared between the tumor and the nervous system are recognized as foreign by the host and elicit an immune response. The immune response is directed appropriately against the tumor leading to a more indolent course in those patients with paraneoplastic syndromes but is misdirected against the nervous system often leading to severe nervous system destruction. The evidence for this hypothesis consists of: 1) The finding of high titer autoantibodies that react with antigens in both tumor and central nervous system. 2) Intrathecal synthesis of the antibody. 3) The presence of the antibody in the central nervous system at autopsy. The development of animal models will be required to determine the exact nature of the pathogenesis of these disorders.

Autoantibodies↗
PubMed1992

The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues.

Using immunohistochemistry or Western blot analysis, the authors have studied the expression of the Hu antigen (a neuronal protein identified by the serum of patients with small cell lung cancer and paraneoplastic encephalomyelitis/sensory neuronopathy) in normal human tissues and 115 tumors of different histologic types. In normal tissue, the Hu antigen is highly restricted to the nervous system. In lung tumors, the Hu antigen is restricted in its expression to all small cell carcinomas. A few other neuroendocrine-related tumors, especially neuroblastomas (50%), also express the antigen.

Carcinoma, Small Cell↗
PubMed1992

Management of brain metastases.

Brain metastases are common and often occur in patients whose systemic cancer is quiescent. When brain metastases occur, they considerably decrease the quality of life in patients who otherwise might be functional. An early diagnosis and vigorous treatment of the brain metastasis, while only rarely curative, may lead to a useful remission of the brain symptoms and may both enhance the quality of the patient's life and prolong survival. Patients with known cancer and neurological symptoms should all undergo appropriate diagnostic tests which include either CT scan or magnetic resonance imaging and, if a lesion is found and a definitive diagnosis can not be established, biopsy. Single or solitary brain metastases in patients with good systemic performance status should be strongly considered for surgical extirpation which will both make the diagnosis and deliver definitive treatment to the lesion. Patients with poor systemic performance status and/or multiple brain metastases are candidates for whole brain radiation therapy. Whole brain radiation therapy is also indicated in patients after successful surgical extirpation of a single metastasis. The role of focal radiation therapy and chemotherapy in the treatment of brain metastases is still being evaluated. Preliminary evidence suggests that focal radiation therapy is probably useful for the treatment of relapsed metastases and that chemotherapy may be useful in the primary treatment of small or asymptomatic brain metastases. Appropriate use of therapeutic modalities directed at brain tumors will ameliorate symptoms in most patients and usually increase survival and enhance the quality of the patient's life.

Adrenal Cortex Hormones↗
PubMed1991

HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal.

A neuronal antigen (HuD) recognized by the sera of patients with antibody-associated paraneoplastic encephalomyelitis has been isolated by screening a lambda cerebellar expression library. The recombinant antigen provides an unambiguous assay for this rare condition associated with small cell lung cancer. The recombinant antigen has been used to identify specific infiltrating lymphocytes in tumors and affected brain tissues of patients with antibody-associated paraneoplastic encephalomyelitis and sensory neuronopathy. HuD mRNA is uniquely expressed in brain tissue. The HuD protein shows a remarkable homology to the Drosophila proteins Elav and Sex-lethal and is likely to play a role in neuron-specific RNA processing.

Amino Acid Sequence↗
PubMed1991

Cloning of a leucine-zipper protein recognized by the sera of patients with antibody-associated paraneoplastic cerebellar degeneration.

Antibody-associated paraneoplastic cerebellar degeneration (the Yo syndrome) is an uncommon disorder in which an immune response is specifically directed against tumor tissue and the cerebellum. Screening of a lambda expression library has resulted in the isolation of cDNA clones that encode the major antigen recognized by serum from these patients. The fusion protein produced by the cDNA clones provides the basis of a simple diagnostic assay for this neurological syndrome. The occurrence of leucine-zipper and zinc-finger motifs in the predicted open reading frame suggests that this protein plays a role in the regulation of gene expression.

Amino Acid Sequence↗
PubMed1991

Increased capillary permeability in rat brain induced by factors secreted by cultured C6 glioma cells: role in peritumoral brain edema.

To investigate whether brain tumors secrete a factor(s) responsible for peritumoral brain edema, we studied the effect of conditioned medium from cultured C6 glioma cells on rat brain capillary permeability. Three different fractions of conditioned medium were obtained. SUP-N was a culture supernatant incubated 4 hours in serum-free medium. SUP-C was the 60-100 fold concentrated fraction obtained by dialysis-concentration of SUP-N; it contained 950 micrograms/ml of protein greater than 10 k-daltons from 3 x 10(8) cells. SUP-L was a water-dispersible lipid fraction from SUP-N; the major components of SUP-L were neutral lipids and free fatty acids. The supernatant fractions and their corresponding control solutions were infused into normal rat brain, and capillary permeability was determined using quantitative autoradiography by measuring the unidirectional entry constant, K (micrograms l/g.min), of 14C-alpha-aminoisobutyric acid (14C-AIB) into brain tissue. SUP-C and SUP-L significantly increased capillary permeability of normal brain; the effect of SUP-C was more intense and extensive than that of SUP-L. The highest mean K value (Kmax) of SUP-C was 10.83 +/- 0.99 and that of the control was 2.53 +/- 0.22 (p less than 0.001). The Kmax of SUP-L was 5.61 +/- 0.23 and that of the control was 2.67 +/- 0.36 (p less than 0.01). A time-course study after infusion of SUP-C demonstrated that more than 1.5 hours is required for the supernatant fraction to open the barrier and that the effect of SUP-C was reversible. The increase of capillary permeability induced by SUP-C was significantly inhibited by pretreatment of rats with dexamethasone (10 mg/kg, ip) 1 hour before intracerebral infusion of SUP-C (Kmax (untreated): 8.30 +/- 0.82, Kmax (treated): 1.33 +/- 0.64, p less than 0.001). These results indicate that experimental brain tumors secrete at least two different diffusible factors responsible for capillary endothelial leakage in normal brain. One is a protein of molecular weight greater than 10 k-daltons, whose effect is inhibited by glucocorticoids, and the other is a waterdispersible lipid.

Animals↗
PubMed1991

Primary leptomeningeal lymphoma: report of 9 cases, diagnosis with immunocytochemical analysis, and review of the literature.

We describe 9 patients who presented with a neoplastic meningitis of lymphomatous origin. No evidence of parenchymal central nervous system or systemic tumor was identified either at the time of presentation or throughout the course of their disease. We have chosen to call this entity "primary leptomeningeal lymphoma" (PLML). This unusual form of neurologic lymphoma must be differentiated from the more common clinical situations of primary parenchymal lymphoma with meningeal involvement and systemic lymphoma complicated by lymphomatous meningitis.

Adult↗
PubMed1991

Detection of the anti-Hu antibody in specific regions of the nervous system and tumor from patients with paraneoplastic encephalomyelitis/sensory neuronopathy.

We studied the nervous systems and tumors of five patients with anti-Hu-positive paraneoplastic encephalomyelitis/sensory neuronopathy (PEM/PSN) to determine if the autoantibody found in the serum and CSF was also present in those tissues. Immunohistochemical studies of the nervous system revealed the presence of IgG bound predominantly to the nuclei of most of the neurons and the cytoplasm of some glial cells. IgG was also present to a lesser degree in the neuropil. In brains of patients who died of cancer without the paraneoplastic syndrome, IgG was present in the immediate perivascular areas and to a very limited degree in the neuropil. There was no IgG in neurons, and in only some of the controls a few glial cells showed IgG immunoreactivity in the cytoplasm. The amount of anti-Hu IgG relative to total IgG in various brain regions and tumor was determined by quantitative Western blot analysis. The proportion of anti-Hu IgG was greater in some areas of the brain and tumor than in serum and CSF. Control brains did not contain anti-Hu IgG. There was a limited correlation among (1) the principal clinical symptoms, (2) regions of major tissue injury, and (3) the quantitative anti-Hu IgG distribution. We conclude that although the role of the antibody in the pathogenesis of the disease is still uncertain, its specific localization in the nervous system and tumor suggests an immunologic etiology of this paraneoplastic syndrome.

Aged↗
PubMed1991

Paraneoplastic syndromes.

The neuromuscular complications of systemic cancer include direct effects (compression or infiltration of peripheral nerve tissues by tumor cells), effects of radiation and chemotherapy, and remote effects. Remote effects constitute the paraneoplastic syndromes--a heterogeneous group of disorders that include motor neuron disease, axon-loss and demyelinating polyneuropathies, Lambert-Eaton myasthenic syndrome, and inflammatory myopathies.

Diagnosis, Differential↗
PubMed1991

Antiserum from a patient with cerebellar degeneration identifies a novel protein in Purkinje cells, cortical neurons, and neuroectodermal tumors.

The serum and cerebrospinal fluid of a patient (NB) with subacute cerebellar degeneration were found to contain a novel antineuronal autoantibody (anti-Nb). Using this antibody, we have identified and characterized antigens present in a subset of neurons in the CNS and in some neuroectodermal tumor lines. Anti-Nb antibody bound to antigens of Mr 150, 120, and 65 kDa in Western blots using extracts of human cerebellar Purkinje cells or human cerebral cortical neurons. Immunohistochemistry demonstrated relatively specific binding of anti-Nb IgG to Purkinje cells in sections of human cerebellum and to some neocortical neurons, especially those in layer VI. Because of the association of cerebellar degeneration with occult malignancies, we screened a number of tumor cell lines for immunoreactivity to anti-Nb antibody; only tumor lines of neuroectodermal origin (melanoma, small-cell lung cancer, and neuroblastoma) expressed the Nb antigen. Anti-Nb antibody thus identifies neuronal and tumor cell antigens that appear to be unique in size and distribution of expression.

Adult↗
PubMed1990

Selective expression of Purkinje-cell antigens in tumor tissue from patients with paraneoplastic cerebellar degeneration.

Paraneoplastic cerebellar degeneration is a rare syndrome that occurs in patients with gynecologic cancer and is characterized by widespread loss of Purkinje cells. To determine whether Purkinje-cell antigens are selectively expressed in the tumors of patients with the syndrome, we examined tumor tissue from 10 patients whose serum contained anti-Purkinje-cell (anti-Yo) antibodies. The origins of the cancers were the breast (five patients), ovary (three), endometrium (one), and fallopian tube (one). We used as controls tumor tissue from 11 patients with ovarian cancer and 10 patients with breast cancer who were neurologically normal. Using immunohistochemical and Western blot analysis, we found that Purkinje-cell antigens were expressed in all the tumors from the 10 patients with paraneoplastic cerebellar degeneration but in none of the tumors from the 21 neurologically normal patients. When IgG from patients with paraneoplastic cerebellar degeneration was affinity-purified to cerebellar Purkinje-cell antigen, immunohistochemical analysis showed that it reacted specifically with the tumor tissue from those patients. We conclude that in patients with paraneoplastic cerebellar degeneration, the anti-Yo antibody results from an immune response to neural antigens expressed by the gynecologic tumors in the patients.

Antigens, Neoplasm↗