Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q.

Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. The neuronal form of this disorder is referred to as Charcot-Marie-Tooth type II disease (CMT2). CMT2 is usually inherited as an autosomal dominant trait with a variable age at onset of symptoms associated with progressive axonal neuropathy.

Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B.

Multiple endocrine neoplasia type 2B (MEN 2B) is a human cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytomas, mucosal neuromas, ganglioneuromas of the intestinal tract, and skeletal and ophthalmic abnormalities. It appears both as an inherited disorder and as de novo disease. Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation in the RET protooncogene in 34 unrelated individuals.

Expression and function of TRK-B and BDNF in human neuroblastomas.

There is considerable interest in the role of the TRK family of neuotrophin receptors in regulating growth and differentiation in normal and neoplastic nerve cells. A neuroblastoma is a common pediatric tumor derived from the neural crest, and the majority of favorable neuroblastomas express a high level of TRK-A mRNA. However, little is known about the expression or function of TRK-B in these tumors.

Expression and function of the nerve growth factor receptor (TRK-A) in human neuroblastoma cell lines.

Nerve growth factor (NGF) is known to play a critical role in the differentiation and survival of normal sympathetic neurons through its interaction with a specific cell surface receptor. We analyzed ten well-characterized neuroblastoma cell lines for the expression and function of endogenous and exogenous p140TRK-A, and p75LNGFR. Exogenous LNGFR or TRK-A (or both) were introduced by transfection into three neuroblastoma cell lines.

Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma.

Background And Methods: The nerve growth factor receptor is expressed in some neuroblastomas, in which its primary component is encoded by the TRK protooncogene. To determine the relation of the expression of TRK messenger RNA in neuroblastomas to other clinical and laboratory variables, we studied frozen tumor samples from 77 patients. In addition, we tested two primary neuroblastomas that expressed TRK for responsiveness to nerve growth factor.

Neuroblastoma. Effect of genetic factors on prognosis and treatment.

BACKGROUND AND METHODS. Genetic analysis of tumor tissue has provided considerable insight into mechanisms of malignant transformation and progression. Neuroblastomas have been studied by cytogenetics, flow cytometry, and molecular genetic techniques, and these studies have identified several specific abnormalities that allow subclassification of these tumors into genetic/clinical subtypes.

Inverse relationship between trk expression and N-myc amplification in human neuroblastomas.

We examined the expression of the trk protooncogene in a series of 82 neuroblastomas to determine its relationship to N-myc amplification and expression, disease stage, patient age, and survival. We found that virtually all stage I, II, and IV-S patients had moderate to high levels of trk expression, whereas most advanced stage neuroblastomas had low or absent levels. All but one tumor with N-myc amplification had low or absent trk expression, and the one exception was regressing at the time it was resected.

Multiple defects of the nerve growth factor receptor in human neuroblastomas.

We hypothesized that defects in the nerve growth factor receptor (NGFR) pathway may play a role in maintenance of the undifferentiated state of neuroblastomas. To test this hypothesis, we examined the structure and function of the NGFR in a panel of 10 neuroblastoma cell lines. Southern blot analysis showed that all 10 cell lines possess apparently normal NGFR genes.

Multiple defects of the nerve growth factor receptor in human neuroblastomas.

Neuroblastoma is a tumor of postganglionic sympathetic origin, and nerve growth factor (NGF) is normally required for the survival and differentiation of sympathetic neuroblasts. Since the biological activity of NGF is mediated by the NGF receptor (NGFR), we hypothesized that defects in the NGF/NGFR pathway may play a role in maintenance of the undifferentiated state of neuroblastomas. To test this hypothesis, we examined the structure of the NGFR at the DNA, RNA, and protein levels in a panel of 10 neuroblastoma cell lines.

Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.

The deduced amino acid sequence of a Drosophila gene isolated with a vertebrate sodium channel complementary DNA probe revealed an organization virtually identical to the vertebrate sodium channel protein; four homologous domains containing all putative membrane-spanning regions are repeated in tandem with connecting linkers of various sizes. All areas of the protein presumed to be critical for channel function show high evolutionary conservation. These include those proposed to function in voltage-sensitive gating, inactivation, and ion selectivity.

Interspecific DNA transformation in Drosophila.

A DNA fragment that includes the wild-type rosy (ry+) gene of Drosophila melanogaster has been introduced by microinjection into the germ line of the reproductively isolated species Drosophila simulans and incorporated into the D. simulans genome. Transformation was mediated by the transposable element P, which occurs in the genome of most natural populations of D.

Drosophila locus with gene-dosage effects on rhodopsin.

Mutations that decrease the amplitude of the prolonged depolarizing afterpotential (PDA) in Drosophila melanogaster have been shown to have reduced rhodopsin content in the rhabdomeres of photoreceptor cells. In the present study, a genetic analysis of a class of third chromosome PDA-defective mutants localized the ninaE locus to the salivary band region 92A-B. In flies with only one copy of this region instead of the normal two copies, and in ninaE heterozygotes, the rhodopsin content of the major class of photoreceptors is reduced.

Effect of age and of screening pigment mutations on the phototactic behavior of Drosophila melanogaster.

Five different eye color mutations of Drosophila melanogaster have been tested for their effect on phototactic behavior. All five mutations seem to cause flies to be less photonegative than Canton-S control flies. The mutation sepia was found to produce this effect when heterozygous as well.