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Biomedical subjects

J Dalmau

Publications and source records attributed to J Dalmau.

At least 127 records · Page 7Linked to original sources
PubMed1994

Paraneoplastic opsoclonus-myoclonus associated with anti-Hu antibody.

We report a 74-year-old woman with opsoclonus, myoclonus, ataxia, and encephalopathy who had small-cell lung cancer and high titers of anti-Hu antibody in her serum. At autopsy, there were perivascular inflammatory infiltrates in the brainstem, putamen, and meninges overlying the orbital frontal cortex. Immunohistochemical studies showed the expression of the Hu antigens by the tumor and the presence of deposits of anti-Hu IgG in the patient's cortex, brainstem, and cerebellum, suggesting that anti-Hu immune response was related to the patient's clinical syndrome. This case of paraneoplastic opsoclonus, myoclonus, ataxia, and encephalopathy expands the spectrum of neurologic dysfunction associated with the anti-Hu antibody.

Aged↗
PubMed1993

The neuronal nuclear antigen recognized by the human anti-Ri autoantibody is expressed in central but not peripheral nervous system neurons.

Anti-Ri is a human autoantibody that recognizes a neuronal nuclear antigen (Ri). Biotinylated IgG from serum of two patients with high titers of anti-Ri antibodies was used to study the distribution of the Ri antigen in a panel of normal human tissues. the expression of the Ri antigen was evaluated by an avidin-biotin peroxidase technique and confirmed by immunoblotting. The Ri antigen was restricted to the neurons of the central nervous system (CNS) and some pituitary cells. Most neurons in dorsal root, Gasserian and sympathetic ganglia, and myenteric plexus were negative or, a few of them, very weakly positive. The functional implication of the different expression of the Ri antigen between neurons of the central and peripheral nervous system is presently unknown.

Antigens↗
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

Improved identification of heterozygotes for phenylketonuria using blood neopterin and biopterin.

A novel approach that combines information provided by the metabolism of pteridines and that of phenylalanine has been applied to the detection of heterozygotes for phenylketonuria. Phenylalanine, tyrosine, biopterin and neopterin have been measured in serum from normal controls and heterozygotes for classical phenylketonuria, before and after a phenylalanine oral load. Significant differences in neopterin and biopterin mean values in fasting serum and in the mean increase of biopterin induced by the phenylalanine load were found between groups. Inclusion of pteridine data in the discriminant analysis significantly improved the resolution of the classical phenylalanine loading test for the detection of heterozygotes for phenylketonuria.

Adult↗
PubMed1993

Paraneoplastic intestinal pseudo-obstruction associated with high titres of Hu autoantibodies.

Anti-Hu autoantibodies in high titres, as revealed with immunocytochemistry and Western blot, were present in a patient with gastrointestinal pseudo-obstruction and small-cell lung cancer (SCLC) bearing the Hu antigen. Marked neuron and nerve fibre loss were found in the myenteric plexus at postmortem. These findings show that neuronopathic Hu-associated gastrointestinal pseudo-obstruction can occur as the only paraneoplastic neurological symptom in patients with SCLC.

Antibodies, Neoplasm↗
PubMed1992

p53 gene mutations in primary lung tumors are conserved in brain metastases.

The p53 product is frequently mutated in human tumors. Both acquired and inherited mutations have been described. These mutations transform p53 from a growth suppressor gene to a transforming oncogene. We examined tissue from 6 patients with primary lung carcinoma and the corresponding brain metastases for the presence of p53 mutations by immunohistochemistry. We then confirmed and characterized the mutations by single strand conformation analysis and by direct sequence analysis. All 6 patients had primary and metastatic tumor expressing a mutant p53. The mutations were all G-T transversions and mapped to exons 5, 6, 7, and 8. The mutations in the primary tumors were precisely conserved in the brain metastases.

Aged↗
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↗
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↗
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

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↗
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↗
PubMed1990

Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer--a quantitative western blot analysis.

We looked for the presence of the anti-Hu antibody in the sera from 50 normal subjects; 44 patients with small cell lung cancer, not associated with paraneoplastic disease; and 25 patients with small cell lung cancer associated with paraneoplastic sensory neuropathy, encephalomyelitis, or both. Using the avidin-biotin immunoperoxidase method and a highly sensitive quantitative Western blot analysis, the anti-Hu antibody was not detected in the 50 normal human sera. Seven of the 44 patients with small cell lung cancer but no paraneoplastic syndrome had detectable levels (average titer, 76 U/ml) of anti-Hu antibody on Western blot. These levels are significantly lower than the average titer of the 25 patients who had small cell lung cancer and paraneoplastic sensory neuropathy or encephalomyelitis (average titer, 4,592 U/ml). In the group with nonparaneoplastic small cell lung cancer (low anti-Hu titer) there was a predominance of women (5 women: 2 men), and all patients had "limited" disease when diagnosed. In the antibody-negative group the sex ratio was 16 women to 21 men and 51% of the patients had "extensive" disease. None of the 7 patients with a low-titer anti-Hu antibody developed a paraneoplastic syndrome by the time of writing. The anti-Hu antibody appears, when present, to be a good marker for small cell lung cancer and, when present at high titer, for small cell lung cancer associated with a paraneoplastic syndrome.

Adult↗