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S L Kinsman

Publications and source records attributed to S L Kinsman.

5 recordsLinked to original sources
PubMed1994

RNA editing of a human glutamate receptor subunit.

AMPA receptors are comprised of individual subunits, and the divalent cation permeability of assembled AMPA receptors is determined by a single amino acid residue in the second transmembrane region of the GluR-B subunit. At this site, GluR-B subunits contain an arginine while other AMPA receptor subunits contain glutamine. Interestingly, the murine gene for GluR-B actually specifies a glutamine at the divalent cation permeability site. The appearance of arginine and not glutamine in the mature GluR-B protein is thought to be a result of RNA editing of the GluR-B messenger RNA. In that AMPA receptors are thought to mediate the bulk of fast excitatory signalling within the mammalian central nervous system, this process of RNA editing may play a pivotal role in normal neural function by mediating divalent cation permeability of AMPA receptors. Disruptions of RNA editing could lead to phenotypically altered AMPA receptors, with implications for pathogenic brain processes. We report that the human GluR-B gene sequence is also edited such that there is a difference between the human GluR-B gene and the complementary DNA (cDNA), as demonstrated both with allele-specific polymerase chain reaction (PCR) and restriction enzyme digestion of PCR products. Thus, as in the rodent brain, RNA editing of an AMPA receptor subunit appears to be an important process in the human brain. Disruptions of RNA editing may have neuropathological consequences.

Base Sequence↗
PubMed1994

A reverse transcription-polymerase chain reaction study of p75 nerve growth factor receptor gene expression in developing rat cerebellum.

The actions of the neurotrophins are mediated through specific receptors. Nerve growth factor (NGF), the prototypic neurotrophin, binds to receptors of both high and low affinity. A protein 75 kDa in size (p75NGFR) binds NGF, as well as brain-derived neurotrophic factor and neurotrophin 3, with low affinity. Recent investigations suggest that this protein may also be a component of the high affinity NGF receptor complex. To study gene expression of the p75NGFR molecule, we used a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay to measure levels of its messenger RNA (mRNA) in small samples of total RNA. The assay is based on using a shortened p75NGFR cRNA as an internal RNA standard to control for variability in reverse transcription and polymerase chain amplification. We measured p75NGFR mRNA levels in the rat cerebellum during ontogeny to further study the transient developmental increase in receptor gene expression known to occur in this brain region during the early postnatal period. We found that p75NGFR mRNA levels were most abundant at postnatal day 2, and then declined to lower levels throughout postnatal development and in the adult. Northern blot analysis of the same total RNA samples used in our RT-PCR assay verified that p75NGFR expression is highest in the early postnatal period. These results confirm those of previous studies accomplished with much larger amounts of RNA using ribonuclease protection or northern blot assays. The use of an RT-PCR assay that utilized an internal standard also controls against changes in RNA complexity which can affect the measurement of message abundance across developmental stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1981

Mauthner axon diameter and impulse conduction velocity decrease with growth of goldfish.

Conduction velocities of antidromically evoked impulses along the goldfish Mauthner axon were found to be inversely correlated with body length. To test the hypothesis that such a relation is accompanied by a reduction in axonal diameter with increasing fish size, Mauthner axon diameters were measured. A parabolic relationship with respect to body length was obtained, axonal diameter being maximal in 9.5 cm fish. To our knowledge, this is the first report of a decrease in conduction velocity and axonal size during growth of an organism were functioning of the cell is maintained.

Aging↗
PubMedDate not supplied

Efficacy of the ketogenic diet for intractable seizure disorders: review of 58 cases.

The ketogenic diet was developed in the 1920s as a treatment for intractable childhood seizures when few antiepileptic drugs (AEDs) were available. There are still children whose seizures are refractory even to modern therapy, but use of the ketogenic diet appears to be waning. At Johns Hopkins, we continue to believe that the diet is very effective and well accepted by patients and families. To reevaluate our opinion of the efficacy and acceptability of this form of therapy in patients cared for in the 1980s with the newer AEDs, we analyzed the records of 58 consecutive patients who had been started on the diet. Before using the diet, 80% of the patients had multiple seizure types and 88% were treated with multiple AEDs; these children were among our most intractable patients. Despite this, seizure control improved in 67% of patients with the ketogenic diet, and actuarial analysis indicated that 75% of these improved patients continued the diet for at least 18 months. Sixty-four percent had AEDs reduced, 36% became more alert, and 23% had improved behavior. The improvement in these patients with intractable seizures and the length of time that families maintained the regimen indicate that the ketogenic diet continues to have a very useful therapeutic role in selected patients and their families.

Adolescent↗