Search PubMed⌕ Search

Biomedical subjects

J B Posner

Publications and source records attributed to J B Posner.

At least 73 records · Page 4Linked to original sources
PubMed1994

Paraneoplastic sensorimotor neuropathy associated with breast cancer.

Paraneoplastic sensorimotor neuropathy occurs in association with many different types of cancer. The clinical findings are heterogeneous, and the pathogenesis is unknown. We have encountered 9 women with breast cancer and shared neurological features that suggest a distinct paraneoplastic syndrome. The syndrome is characterized by upper and lower extremity paresthesias and numbness, itching, muscle weakness and cramps, and in some, radicular symptoms and signs. Serum and CSF inflammatory changes suggested an immune pathogenesis but none had detectable antibodies directed at nervous system elements. Six patients presented with neuropathy 2 months to 8 years before the discovery of the breast cancer. In 7 the neoplastic disease was localized to the breast and axillary lymph nodes. The neurologic course was chronic in all, and while symptoms were annoying, disability was minimal until late. One improved transiently with plasmapheresis, and three had mild transient improvement with treatment of the cancer. Recognition of this paraneoplastic syndrome may forewarn the physician of an underlying breast malignancy.

Adenocarcinoma↗
PubMed1994

Mutant herpes simplex virus induced regression of tumors growing in immunocompetent rats.

Herpes simplex virus (HSV) mutants kill dividing tumor cells but spare non-proliferating, healthy brain tissue and may be useful in developing new treatment strategies for malignant brain tumors. Two HSV mutants, a thymidine kinase deficient virus (TK-) and a ribonucleotide reductase mutant (RR-), killed 7/7 human tumor cell lines in tissue culture. The TK-HSV killed Rat RG2 glioma and W256 carcinoma lines but not the rat C6 glioma in culture. TK-HSV replication (12 pfu/cell) was similar to wild-type HSV (10 pfu/cell) in rapidly dividing W256 cells in tissue culture, but was minimal (< 1 pfu/cell) in serum-starved cells, suggesting that the proliferative activity of tumor cells at the site and time of TK-HSV injection may influence efficacy in vivo. Subcutaneous W256 tumors in male Sprague-Dawley rats were injected with TK-HSV or free inoculum. A significant effect of TK-HSV therapy on W256 tumor growth was demonstrated compared to controls (p = 0.002). Complete regression was observed in 4/9 experimental tumors, with no recurrence over 6 months. Tumor growth in the remaining 5/9 animals was attenuated during the first 3 to 5 days after treatment, but not beyond 5 days compared to 9 matched control animals; no tumor regression was observed in any of the control animals. These results suggest that HSV mutants are potentially useful as novel therapeutic agents in the treatment of tumors in immunocompetent subjects.

Animals↗
PubMed1994

Mapping of the gene coding for a paraneoplastic encephalomyelitis antigen (HuD) to human chromosome site 1p34.

A cDNA clone coding for a human brain protein (HuD), which is highly homologous to the Drosophila neuronal determination protein Elav and elicits antibody formation in a high proportion of patients with paraneoplastic encephalomyelitis, was used to isolate a lambda phage recombinant clone, including a large fragment of the relevant human genomic region. The fragment proved to be an efficient probe for the precise subregional mapping of the gene by molecular in situ hybridization onto extended human prometaphase chromosomes. Analysis of banded metaphases with clear hybridization signals pointed unequivocally to the localization of the HuD gene to human chromosome band 1p34.

Chromosome Mapping↗
PubMed1994

Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis.

Using immunohistochemistry, we studied the IgG subclass distribution of the anti-Hu antibody in serum, nervous system, and tumor of patients with anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN). The nervous system was also examined for deposits of complement and the distribution and type of inflammatory cells. IgG1 and IgG3 were the predominant isotypes of the anti-Hu IgG in serum, nervous system, and tumor. A few patients also had anti-Hu IgG2, but this isotype was not consistently present in all the regions of the nervous system studied. There was no correlation between neurologic symptoms and specific anti-Hu isotype, nor was there evidence that different anti-Hu isotypes recognized specific brain regions. Although IgG1 and IgG3 can activate complement, only weak complement reactivity was found, and that only in a few areas of the nervous system. This finding, in addition to the absence of natural killer (NK) cells, suggested that complement-mediated toxicity and antibody-dependent cell cytotoxicity mediated by NK cells are not pathogenic in PEM/PSN. Inflammatory infiltrates included CD19+ (B cells) and CD4+ (helper/inducer) cells in the perivascular spaces, and lymphocytes bearing CD8+CD11b- markers (cytotoxic T cells) in the interstitial spaces. Infiltrates of EBM11+ (monocyte/macrophage) cells were identified in the perivascular spaces (macrophage phenotype) and in those interstitial regions (microglial phenotype) with severe pathologic changes. The ability of the IgG1 and IgG3 isotypes to bind Fc receptors may have played a role in the recruitment of these monocyte/macrophage cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1994

Paraneoplastic temporal lobe epilepsy with testicular neoplasm and atypical amnesia.

We report a patient who, at age 38, presented with temporal lobe seizures and an atypical memory disorder 3 years before the discovery of a testicular tumor. Detailed neuropsychological testing revealed a relatively isolated amnestic syndrome. The amnesia was atypical as the patient could retain information for hour-long periods, only to lose it later. Serologic studies revealed the presence of a circulating autoantibody that demonstrated an unusual affinity for the nucleolus of cerebral cortical neurons. Western blot analysis of cortical neurons revealed that this antibody reacted with proteins different from other previously identified paraneoplastic neurologic antigens (Hu, Yo, Ri). We believe this to be a case of paraneoplastic limbic encephalitis secondary to the testicular tumor. This patient presents unique characteristics with respect to the mode of presentation, features of the amnesia, and the presence of a circulating antibody with an unusual reactivity pattern.

Amnesia↗
PubMed1993

Cloning and characterization of a Lambert-Eaton myasthenic syndrome antigen.

Lambert-Eaton myasthenic syndrome is a paraneoplastic neuromuscular disorder in which an immune response directed against a small-cell lung tumor crossreacts with antigens in the neuromuscular junction. To isolate and characterize the antigens, we screened a human fetal brain expression library with a high-titer serum from a patient with Lambert-Eaton myasthenic syndrome. This screening resulted in the isolation of a complementary DNA clone encoding an antigen we call myasthenic syndrome antigen B (MysB). Approximately 43% (3 of 7) of Lambert-Eaton myasthenic syndrome sera specifically recognized MysB fusion protein, whereas none of 34 control sera did. The predicted amino acid sequence of this clone shows a high degree of homology to the beta subunit of calcium channel complexes. The MysB pre-messenger RNA is alternatively spliced to yield 3 forms of the protein differing in the domain between two highly conserved alpha-helical segments.

Antigens↗
PubMed1993

Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system.

Paraneoplastic opsoclonus-ataxia, a disorder of motor control, develops in breast or lung cancer patients who harbor an antibody (Ri) that recognizes their tumors and a nuclear neuronal protein of 55 kd. We have characterized a gene, Nova, encoding an antigen recognized by the Ri antibody. Nova encodes a novel, highly conserved protein, homologous to the RNA-binding protein hnRNP K, the yeast splicing protein MER1, and a motif in several retroviral proteases. Northern blot analysis detects Nova transcripts only in brain, and several alternatively spliced forms are present in brain and tumor cells. Nova expression is restricted to the ventral brain stem and spinal cord in E18 mice. Since Nova encodes a target antigen in the motor disorder paraneoplastic opsoclonus-ataxia that is expressed in the developing subcortical motor system, it is a likely participant in both the pathogenesis of paraneoplastic opsoclonus-ataxia and the developmental biology of the motor system. The homology between Nova and hnRNP K suggests that Nova regulates RNA splicing or metabolism in a specific subset of developing neurons.

Amino Acid Sequence↗
PubMed1993

Effect of brain irradiation on demyelinating lesions.

Demyelinating lesions, such as those in multiple sclerosis, may resemble primary or metastatic brain tumors on CT or MRI, and even be mistaken for neoplasms on biopsy. We encountered five such patients in whom an incorrect diagnosis of CNS neoplasm was made on the basis of radiologic appearance (five) and biopsy (four). All five received radiation therapy, and three chemotherapy. Review of the pathologic findings indicated that the original lesions were not neoplastic but demyelinative. The four patients who received radiation in full tumoricidal doses had unexpectedly poor clinical outcome, suggesting that radiation is especially injurious to patients with demyelinating disease.

Adult↗
PubMed1993

Novel brainstem syndrome associated with prostate carcinoma.

Two patients successfully treated for prostatic cancer developed a progressive neurologic syndrome beginning with loss of voluntary horizontal eye movements followed by severe, persistent muscle spasms of the face, jaw, and pharynx. Both had mild gait unsteadiness, and one exhibited facial and abdominal myoclonus. Extensive diagnostic studies, including MRIs of the brainstem (with and without contrast), were normal. CSF examination showed mild pleocytosis and elevated IgG. Quantitative eye movement recordings documented selective involvement of voluntary horizontal saccades with sparing of horizontal slow eye movements. Neither patient had antineuronal antibodies in the blood. Postmortem examination revealed perivascular chronic inflammatory cells and microglial infiltration of the pons and medulla. One patient also had perivascular infiltrates in both mesial temporal lobes. Neuronal loss was localized to the pontine tegmentum, the medullary sensory nuclei, and the cerebellum. Brainstem motor nuclei were preserved. The clinical and pathologic findings suggest an autoimmune process (probably paraneoplastic) with selective damage to a subpopulation of brainstem neurons critical for horizontal eye movements and recurrent inhibition of bulbar nuclei.

Adenocarcinoma↗
PubMed1993

MRI changes in intracranial hypotension.

We report seven patients with the syndrome of intracranial hypotension who were referred to Memorial Sloan-Kettering, primarily because of suspicion of meningeal tumor or infection raised by the finding of meningeal enhancement on MRI. In three patients, symptoms occurred after lumbar puncture; in four, there was no clear precipitating event. Lumbar puncture after MRI in six patients revealed low CSF pressure (six patients) and pleocytosis or high protein, or both (four patients). Three patients had subdural effusions. Six patients had measurable descent of the brain on midsagittal images. Postural headache resolved in all seven patients, six of whom had follow-up MRIs. Meningeal enhancement resolved or diminished in all six. Subdural effusions resolved spontaneously in two and were evacuated (but were not under pressure) in one. Downward brain displacement improved or resolved in all patients. The clinical syndrome and MRI abnormalities generally resolve on their own. An extensive workup is not helpful and may be misleading. Patients should be treated symptomatically.

Adult↗
PubMed1993

Headaches in patients with brain tumors: a study of 111 patients.

We examined 111 consecutive patients with primary or metastatic brain tumors identified by CT or MRI to characterize brain tumor headache. The median age was 44 years; 34% had primary and 66% metastatic tumors. Headaches were present in 48%, equally for primary and metastatic brain tumors. Headaches were similar to tension-type in 77%, migraine-type in 9%, and other types in 14%. The typical headache was bifrontal but worse ipsilaterally, and was the worst symptom in only 45% of patients. Unlike true tension-type headaches, brain tumor headaches were worse with bending over in 32%, and nausea or vomiting was present in 40% of patients. The "classic" early morning brain tumor headache is uncommon. Nausea, vomiting, an abnormal neurologic examination, or a significant, change in prior headache pattern suggest that the headache may be caused by a tumor.

Brain Neoplasms↗
PubMed1993

Paraneoplastic cerebellar degeneration.

Paraneoplastic cerebellar degeneration is a rare complication of a number of cancers, particularly small cell lung cancer, gynecologic cancers and Hodgkin's disease. The disorder is clinically characterized by rapid development of pancerebellar dysfunction, which usually does not improve, and pathologically characterized by loss of Purkinje cells with or without inflammatory infiltrates. In some but not all patients, an autoantibody that reacts with the tumor and Purkinje cells can be found in the serum and spinal fluid of patients with paraneoplastic cerebellar degeneration. The presence of the autoantibody suggests, but does not prove, that the disorder has an autoimmune mechanism for its pathogenesis.

Humans↗
PubMed1992

The spectrum of neurological disease in patients with systemic cancer.

To ascertain the range of neurological problems in patients with systemic cancer, we prospectively evaluated neurological symptoms, neurological diagnoses, and primary tumors in all patients with a history of systemic cancer examined by the Department of Neurology at the Memorial Sloan-Kettering Cancer Center, from Jul 1, 1990, to Dec 31, 1990. Of the 815 patients seen for neurological symptoms, less than half (45.2%) had metastatic involvement of the nervous system. The three most common symptoms were back pain (18.2%), altered mental status (17.1%), and headache (15.4%). The most common neurological diagnosis was brain metastasis (15.9%), followed by metabolic encephalopathy (10.2%), pain associated with bone metastases only (9.9%), and epidural extension or metastasis of tumor (8.4%). Of 133 patients with undiagnosed back or neck pain, 44 (33%) had epidural extension or metastases from tumor and 40 (30%) had pain associated with vertebral metastases only. In 15 (11%) the cause for the back pain was unrelated to metastatic disease. Of 132 patients seen on initial consultation for altered mental status, metabolic encephalopathy was the major neurological diagnosis (80; 61%); 20 (15%) had intracranial metastases. Of 97 patients with undiagnosed headache, 59 (61%) had a nonstructural cause. Fifty-three of these patients had either migraine, tension headache, or headache related to systemic illness (e.g., fever, sepsis). These results indicate that even in patients with systemic cancer, a group particularly prone to developing neurological disease that can be diagnosed radiologically, the role of clinicians remains important in helping distinguish noncancer-related and nonmetastatic neurological problems.

Adult↗
PubMed1992

P-glycoprotein expression in brain tumors.

Overexpression of P-glycoprotein (P-gp) in cancer cells can result in resistance to several chemotherapy agents (multidrug resistance) including doxorubicin and vincristine. The drugs to which resistance develops also penetrate the blood brain barrier poorly. P-gp expression in brain capillary endothelial cells suggests that P-gp may restrict drug entry into brain tumors and thus be another mechanism of drug resistance. To seek evidence for either of these roles in the drug resistance of brain tumors, we examined the location of expression of P-gp in 49 brain tumors, using an anti-P-gp mouse monoclonal antibody and immunohistochemistry. P-gp expression was observed in tumor cells of two glioblastomas and a meningeal sarcoma but not in low-grade primary or metastatic tumors. In low-grade primary tumors, P-gp was present in all vascular endothelial cells. In the vascular endothelial cells of anaplastic primary brain tumors and brain metastases, P-gp expression was heterogeneous or absent. These findings are consistent with a role for P-gp in the resistance of some brain tumors to chemotherapy agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

In situ mapping of the gene coding for a leucine zipper DNA binding protein (CDR62) to 16p12-16p13.1.

A cDNA clone encoding the major antigen (CDR62) associated with the antibody-induced paraneoplastic cerebellar degeneration has been used to identify the chromosomal location of the corresponding structural gene(s) by screening for its retention in a panel of rodent-human somatic cell hybrids. Having established the synteny of the gene with the autosome 16, we proceeded to its precise subregional mapping by in situ fluorescence hybridization with a recombinant lambda phage containing the genomic region homologous to the cDNA gene. The latter studies pin-pointed the chromosomal localization of the structural CDR62 gene within the interval 16p12-16p13.1.

Chromosome Banding↗
PubMed1992

Anti-Hu--associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients.

We studied 71 patients with "paraneoplastic" encephalomyelitis, sensory neuronopathy, or both associated with the presence of the anti-Hu antibody in their serum. Most (78%) had small-cell lung cancer. In 9 patients no tumor was detected. Fifty-two patients (73%) had signs and symptoms of multifocal involvement of the nervous system; in 28 (39%), 2 areas, and in 24 (34%), 3 or more areas were clinically affected. Sensory neuronopathy was present in 52 patients (74%), but in only 44 (62%) did it dominate the course of the disease. Other predominant findings were: motor neuron dysfunction (14 patients, 20%), limbic encephalopathy (14, 20%), cerebellar symptoms (11, 15%), brainstem encephalopathy (10, 14%), and autonomic nervous system dysfunction (7, 10%). The presence of the anti-Hu antibody prompted a search for the tumor in 60% of the patients; the tumor when found was usually small and remained localized until death, or was demonstrated only at autopsy. Treatment using steroids and plasmapheresis, immunosuppressants, or both, did not improve the paraneoplastic symptoms. Autonomic and respiratory failure, either of central origin or secondary to neuromuscular weakness, were the principal causes of death. Patients with rapidly developing sensory neuropathy or symptoms of encephalomyelitis should be studied for the presence of the anti-Hu antibody; if the antibody is found, the possibility of small-cell lung cancer should be investigated. If a tumor is not found in the initial search, one may become evident in several months.

Adolescent↗