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Biomedical subjects

H A Hartmann

Publications and source records attributed to H A Hartmann.

At least 19 recordsLinked to original sources
PubMed1992

Regional mRNA changes in brain stem motor neurons from patients with amyotrophic lateral sclerosis.

An antisense oligonucleotide (54 mer) from the mRNA to the midsize neurofilament protein (NFM) was labeled with 35S on the 3' end and purified by polyacrylamide gel electrophoresis (PAGE). In situ hybridization was performed on sections from medulla oblongata of patients with amyotrophic lateral sclerosis (ALS). The slides were dipped in photographic emulsion, developed, and stained. Neurons from both nucleus hypoglossus and nucleus ambiguous showed a marked reduction of silver grains when compared to normal. This indicates a reduction of mRNA, which may precede the reduction of ribosomal RNA and the changes in neurofilament proteins that have been described by several investigators in ALS. It does not settle the question of whether the reduction of mRNA is owing to reduced transcription or increased decay of mRNA.

Aged↗
PubMed1992

Deficiency of copper can cause neuronal degeneration.

The aim of this article is to emphasize the important role that copper plays in the function of nerve cells. We are reporting preliminary data which suggest that the swelling of axons which we produce in rats by iminodipropionitrile, IDPN, is due to its chelating action on copper, and how conversely supplementation with copper abolishes both symptoms and lesions. The copper values we obtained by atomic absorption spectrophotometry of the spinal cord and brain from the animals fully support this contention. In comparing these results with the diseases that are known to be due to copper deficiency, namely Menkes disease in man, swayback in lambs and several neurological mutant mice, we find not only similar axonal swellings, but also amelioration of symptoms and lesions by early administration of copper. Considering the main forms in which copper is present, we discuss the cuproproteins, i.e. ceruloplasmin and metallothionein, and their role in transport and delivery of copper to various organs. Further, the many cuproenzymes i.e. superoxide dismutase, tryptophan-2,3-dioxygenase, lysine oxidase, cytochrome oxidase, monoamine oxidases, tyrosinase, dopamine-beta-hydroxylase and d-amino levulinate dehydratase are noted for their roles in the nervous system. Finally, we suggest that neuronal copper deficiency should be more fully investigated as a possible etiological factor in the more common neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis, ALS.

Animals↗
PubMed1992

Differences between the deep pores of K+ channels determined by an interacting pair of nonpolar amino acids.

The pore of a chimeric K+ channel, CHM, differed from its parental host channel, Kv2.1, by 9 amino acids. Four were located in a putative deep region and 5 in a nearby outer mouth. Point reversions were without restorative effects, and reversions V369I or L374V in the deep pore produced novel phenotypes. Among double mutations, only V369I and L374V were effective in restoring the Kv2.1 pore phenotype. Adding a change in charge at Q382K in the outer pore fully restored the parental phenotype. Thus, the pore appears to have an inner, deep region where ions such as K+ and TEA+ may be regulated by nonpolar residues and an outer region where ions may be regulated by charged residues.

Amino Acid Sequence↗
PubMed1992

A single nonpolar residue in the deep pore of related K+ channels acts as a K+:Rb+ conductance switch.

K+ and Rb+ conductances (GK+ and GRb+) were investigated in two delayed rectifier K+ channels (Kv2.1 and Kv3.1) cloned from rat brain and a chimera (CHM) of the two channels formed by replacing the putative pore region of Kv2.1 with that of Kv3.1. CHM displayed ion conduction properties which resembled Kv3.1. In CHM, GK+ was three times greater than that of Kv2.1 and GRb+/GK+ = 0.3 (compared with 1.5 and 0.7, respectively, in Kv2.1 and Kv3.1). A point mutation in CHM L374V, which restored 374 to its Kv2.1 identity, switched the K+/Rb+ conductance profiles so that GK+ was reduced fourfold, GRb+ was increased twofold, and GRb+/GK+ = 2.8. Quantitative restoration of the Kv2.1 K+/Rb+ profiles, however, required simultaneous point mutations at three nonadjacent residues suggesting the possibility of interactions between residues within the pore. The importance of leucine at position 374 was verified when reciprocal changes in K+/Rb+ conductances were produced by the mutation of V374L in Kv2.1 (GK+ was increased threefold, GRb+ was decreased threefold, and GRb+/GK+ = 0.2). We conclude that position 374 is responsible for differences in GK+ and GRb+ between Kv2.1 and Kv3.1 and, given its location near residues critical for block by internal tetraethylammonium, may be part of a cation binding site deep within the pore.

Amino Acid Sequence↗
PubMed1992

Differential expression of the alpha 2 and beta messenger RNAs of Na,K-ATPase in developing brine shrimp as measured by in situ hybridization.

We used in situ hybridization histochemistry with synthetic oligonucleotide probes to localize the mRNAs encoding the alpha 2- and beta-mRNAs of Na,K-ATPase during development of the brine shrimp Artemia. The mRNAs of the alpha 2- and beta-subunit were of low abundance in the cysts; in addition, less mRNA of the beta-subunit was localized. During emergence (12 hr), there was an increase in alpha 2-subunit mRNA in the gut mucosa, but there was a burst in beta-subunit mRNA throughout. As development progressed, the mRNAs of both the alpha 2- and beta-subunits showed a distinct pattern of expression in which the mRNA in the salt gland was of greatest abundance, followed by epidermal cells and gut mucosa. After 36 hr the alpha 2-subunit mRNA began to decrease in all positive cells but still remained highest in the salt gland and the brain region, while the mRNA of the beta-subunit kept increasing in the gut mucosa. Finally, the greatest abundance of the beta-subunit mRNA shifted from the salt gland to the antenna gland and the epidermal cells in the tail region, but the alpha 2-subunit mRNA did not. The more widespread distribution of the beta-mRNA than alpha 2-mRNA at certain stages (e.g., there was no alpha 2-mRNA in the antenna gland at the adult stage) is in all likelihood due to the marked drop in the alpha 2-subunit and a rise in alpha 1-subunit previously seen by Peterson et al. on polyacrylamide gel electrophoresis, as development progresses.

Animals↗
PubMed1991

Exchange of conduction pathways between two related K+ channels.

The structure of the ion conduction pathway or pore of voltage-gated ion channels is unknown, although the linker between the membrane spanning segments S5 and S6 has been suggested to form part of the pore in potassium channels. To test whether this region controls potassium channel conduction, a 21-amino acid segment of the S5-S6 linker was transplanted from the voltage-activated potassium channel NGK2 to another potassium channel DRK1, which has very different pore properties. In the resulting chimeric channel, the single channel conductance and blockade by external and internal tetraethylammonium (TEA) ion were characteristic of the donor NGK2 channel. Thus, this 21-amino acid segment controls the essential biophysical properties of the pore and may form the conduction pathway of these potassium channels.

Amino Acid Sequence↗
PubMed1991

Na,K-ATPase expression in the developing brine shrimp Artemia. Immunochemical localization of the alpha- and beta-subunits.

Developing brine shrimp are a good experimental model for study of gene expression during development. Development is initiated on suspension of brine shrimp cysts in seawater. Only 48 hr are required for progression from cyst to the larval stage. We have localize the alpha- and beta-subunits in different cells by immunostaining as development progresses. Both alpha- and beta-subunits are first detected in epidermal cells in the trunk region at the emergence 2 stage (16-hr incubation). At the nauplius 1 stage (24 hr) the enzyme appears in the brain and epidermal regions, as well as in mesenchymal cells, with weaker staining in the salt gland. After further development (nauplius 2 stage, 36 hr) stronger staining appears in the salt gland and in the epidermal region. At the nauplius 3 stage (48 hr) the enzyme appears in the midgut mucosa. Co-localization of the alpha- and beta-subunits appears in all positive cells during development. In the epidermal and salt gland cells the enzyme is mainly localized on the basolateral membrane. The basolateral localization of the Na,K-ATPase in epidermal and salt gland cells suggests that Na+ is actively transported into the epidermal and salt gland cells and passively diffuses out from the apical region.

Animals↗
PubMed1989

Neuronal RNA in nucleus ambiguus and nucleus hypoglossus of patients with amyotrophic lateral sclerosis.

To establish objectively the involvement of neurons in the medulla oblongata in patients with amyotrophic lateral sclerosis (ALS), ribonucleic acid (RNA) content was determined in neurons of the hypoglossal nucleus and the nucleus ambiguus. Neurons from those two nuclei showed a significant loss of RNA content in patients with ALS; only 57% and 38% of the normal RNA content was found in hypoglossal and ambiguus neurons, respectively. This marked loss of neuronal RNA suggests changes in functional states of neurons, which may contribute to fasciculations in the tongue and difficulties in swallowing often associated with ALS.

Adult↗
PubMed1988

Effects of phenylephrine on calcium current and contractility of feline ventricular myocytes.

Previous studies on numerous cardiac preparations have shown that stimulation of alpha 1-receptors produces a positive inotropic effect. The cellular basis for this effect is not well understood. Isolated feline ventricular myocytes were used in the present study to examine the idea that the increase in contractility induced by stimulation of alpha 1-receptors is produced by an increase in inward Ca2+ current and that this event is caused by the stimulation of protein kinase C (PKC). These experiments showed that phenylephrine (10(-4) M) increased Ca2+ current from 0.56 +/- 0.02 (control) to 1.12 +/- 0.25 nA and increased contractile magnitude by 201 +/- 28%. The effect on Ca2+ current was completely blocked by propranolol (10(-7)M), whereas after beta-receptor blockade, contractile state was still 130 +/- 8% of control levels. alpha 1-Receptor blockade by prazosin eliminated this residual inotropic component of phenylephrine. Lower concentrations of phenylephrine (10(-7)M) were without effect on Ca2+ current and contractility as was stimulation of PCK with 150 nM of a phorbol ester. These results suggest that the positive inotropic effect of alpha 1-receptor stimulation in adult feline ventricular myocytes is not produced by increasing inward Ca2+ current and that this response is also not associated with stimulation of PKC.

Animals↗
PubMed1987

Drowning of a Friedreich's ataxia patient.

We here report an unusual, apparently accidental death, in which weakness associated with a progressive neuromuscular disease, Friedreich's ataxia, apparently resulted in the drowning of the deceased. The possibility of neuromuscular disease as a rare cause of drownings should not be overlooked.

Adult↗
PubMed1986

Multiple myeloma with unusual intracranial manifestations.

We report a unique case of meningeal involvement of multiple myeloma in a 49-year-old man. The patient developed weakness late in the course of his disease, and a computed tomographic scan revealed intracranial masses. At postmortem examination these tumors were the predominant extramedullary manifestation of the patient's anaplastic myeloma. To our knowledge this is the first case of intracranial myeloma composed of multiple, discrete masses.

Adult↗
PubMed1978

RNA content and volume of nerve cell bodies in human brain. I. Prefrontal cortex in aging normal and demented patients.

The age-related change in the neuronal RNA content, volume, and the RNA concentration of 2,160 single cell bodies was examined from the prefrontal cortex. Human brains from 15 normal and 3 demented patients of ages ranging from 8 months to 94 years were obtained at post-mortem examination. The neuronal RNA showed an adult level at age 9 years and remained unchanged until age 66; the mean RNA content was 27.15 pg during this period of time. A decline in the RNA content followed with increasing ages, but it leveled off to an average of 17.97 pg after the age of 80 years. A comparative observation of morphological changes of normal and demented patients reveal the quantitative spectrum of senile plaques. In spite of the presence of significantly more senile plaques, patients with senile dementia showed the RNA content and the volume of the cell body like those of normal patients of similar age. There seems to be no criterion which is characteristic of senile dementia in terms of the RNA content in cortical cell bodies.

Adolescent↗
PubMed1975

Generalized gangliosidosis type II (juvenile GM1 gangliosidosis). A pathological, histochemical and ultrastructural study.

Pathological, histochemical and ultrastructural studies on 3 siblings with GM1 gangliosidosis type II are reported. These studies support a biochemical defect with profound deficiency of beta-galactosidases which results in widespread accumulation of the GM1 ganglioside and its asialo derivative in brain and to a lesser extent in viscera, as well as in storage of a keratan sulphate-like mucopolysaccharide. Striking valvular changes in the heart without myocardial involvement were seen in all cases. The histochemical and ultrastructural changes are similar to those seen in GM1 gangliosidosis type I, though less severe. Autosomal recessive inheritance without apparent ethnic predilection seems likely.

Autopsy↗