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Biomedical subjects

R B Darnell

Publications and source records attributed to R B Darnell.

42 records · Page 3Linked to original sources
PubMed1993

A novel antineuronal antibody in stiff-man syndrome.

Two-thirds of stiff-man syndrome (SMS) patients harbor an autoantibody specific for a 64-kD species of glutamic acid decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis. We assayed SMS antisera from two patients with SMS for the presence of anti-GAD antibodies using Western blot, immunohistochemical, and enzymatic analyses. Both SMS antisera recognized an 80-kD antigen present in human and rat neuronal extracts, and failed to recognize the 64-kD GAD species. Immunohistochemistry demonstrated neuronal binding identical to that reported with anti-GAD antibodies. Both sera depleted GAD activity from brain extracts. Our analysis indicates that these SMS antisera differ from previously reported SMS antisera by recognizing a novel 80-kD antigen, and suggests that they contain antibodies directed against either a species of GAD different in size from the 64-kD enzyme, or a protein that co-immunoprecipitates with GAD.

Adult↗
PubMed1993

Reversible diencephalic dysfunction: episodic hyperhidrosis due to a trapped third ventricle.

We present a patient with episodic hyperhidrosis (EH) who had 15 attacks per day for 3 years following placement of a lateral ventricular shunt. MRI revealed that she had an isolated third ventricle. Stereotactic shunting of the third ventricle resulted in immediate and complete resolution of her symptoms. We suggest that this patient had periodic rises in third ventricular pressure resulting in episodic diencephalic dysfunction and EH.

Aged↗
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↗
PubMed1985

Differential expression of the human gonadotropin alpha gene in ectopic and eutopic cells.

We have analyzed the regulation of the alpha gonadotropin gene in eutopic placental cells and ectopic tumor cells by constructing a series of plasmid vectors containing alpha genomic 5' flanking DNA placed upstream of the gene encoding the bacterial enzyme chloramphenicol acetyltransferase (CAT). These plasmid DNAs were transfected into a eutopic (JAr) and an ectopic (HeLa) cell line. Both cell types expressed the CAT gene from plasmid constructs containing as much as 1,500 base pairs (bp) and as little as 140 bp of alpha 5' flanking DNA; JAr cells were considerably more efficient than HeLa cells. Ectopic and eutopic cells differed qualitatively in their expression from these alpha-CAT constructs when cells were treated with cAMP or butyrate. Butyrate induced alpha expression in HeLa cells but not in JAr cells, while cAMP induced expression in JAr cells. These results are consistent with and extend previous observations suggesting that there are cell-specific differences in the regulation of alpha gene expression in ectopic and eutopic cells. However, by using deletion constructs of the alpha-CAT gene, we found that the basal expression and cell-specific induction of the alpha gene in ectopic and eutopic cells were dependent on the same 140 bp of alpha 5' flanking DNA. These 140 bp were sequenced and found to contain a 9-bp stretch of DNA homologous with the consensus viral enhancer sequence. Such features of alpha expression common to both ectopic and eutopic cells may be involved in the coordinate expression of the alpha gene and the tumorigenic phenotype observed in each cell type.

Acetyltransferases↗
PubMed1984

Independent regulation by sodium butyrate of gonadotropin alpha gene expression and cell cycle progression in HeLa cells.

Sodium butyrate alters the growth and gene expression of a variety of differentiating and neoplastic cell types. For example, addition of 5 mM butyrate to HeLa cells is reported to both induce gonadotropin alpha subunit biosynthesis and block cell cycling in G1. We have studied these two actions of butyrate on HeLa cells and found that they are regulated in distinct ways. The induction of alpha subunit synthesis was due to an increase in the rate of transcription of the alpha gene. Using synchronized populations of HeLa cells, we determined that butyrate stimulates alpha transcription throughout the cell cycle. In contrast, treated cells arrest in G1 only if exposed to butyrate for a discrete period during the previous S phase. We conclude that butyrate inhibits DNA synthesis through a cell cycle-specific action that is independent from its direct action to stimulate transcription of the gonadotropin alpha gene.

Butyrates↗