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Biomedical subjects

A H Koeppen

Publications and source records attributed to A H Koeppen.

At least 37 records · Page 2Linked to original sources
PubMed1991

The Purkinje cell and its afferents in human hereditary ataxia.

The cerebellar cortex in patients with autosomal dominant and recessive ataxia was studied by Golgi impregnation and immunocytochemistry in order to gain further insight into the pathogenesis of neuronal atrophy which accompanies these disorders. Monoclonal antisera were used to visualize phosphorylated and non-phosphorylated neurofilament proteins, and a synapse-specific protein (P38; synaptophysin). Golgi stain and immunocytochemistry for non-phosphorylated neurofilament protein revealed partial or complete loss of distal Purkinje cell dendrities in the dominant cases and in one recessive case. Many preserved parallel fibres were shown by the monoclonal antibody to phosphorylated neurofilament protein. This antibody also gave strong reaction product in torpedoes. Axosomatic and axodendritic terminals on Purkinje cells were reduced in number, and loss of mossy fiber terminals was revealed by monoclonal anti-P38. The described methods provided additional morphological evidence of the heterogeneity of the hereditary ataxias. Purkinje cell atrophy progressed from loss and simplification of the dendritic tree to disappearance of the cell body. While these cells appeared to be especially vulnerable, other neurons of the molecular and granular layers were not exempt. There was evidence that at least some extracerebellar afferents, such as mossy fibers, were also affected by the disease process.

Adult↗
PubMed1991

Experimental superficial siderosis of the central nervous system. I. Morphological observations.

Autologous washed red blood cells were injected weekly over a period of three to six months into the cisterna magna of adult New Zealand white rabbits. After three months, the surface of the brain stem, cerebellum, and piriform cortex showed a distinct brown color, and staining of the gross specimens for iron produced an intense blue color which extended for a distance of 1-2 mm into the brain parenchyma. Enhanced iron stains of vibratome sections revealed the accumulation of reaction product in microglia and Bergmann glia of the cerebellar cortex, and in microglia and astrocytes of the piriform cortex. Ferritin immunocytochemistry revealed reaction product in cerebellar microglia and Bergmann glia which strongly resembled that obtained by the enhanced iron stain. In the piriform cortex, only microglia were reactive with anti-ferritin. Electron microscopy confirmed the accumulation of electron-dense ferritin granules only in the cytoplasm of microglia. Bergmann glia in the cerebellum and astrocytic processes in the piriform cortex were replete with intermediate filaments and contained an excess of glycogen. After six months, small granules of hemosiderin began to appear in cerebellar and piriform cortices. The observations support that the sequence of conversion of hemoglobin to ferritin and hemosiderin occurs in brain as in other organs.

Animals↗
PubMed1990

Familial amyloid polyneuropathy: alanine-for-threonine substitution in the transthyretin (prealbumin) molecule.

A previously reported family with amyloid polyneuropathy (FAP) was reinvestigated to determine the type of mutation in the transthyretin (prealbumin) molecule. Transthyretin was isolated from amyloid-laden myocardium and serum, and tryptic peptides were resolved by high-performance liquid chromatography. Amino acid sequencing of an anomalous peptide revealed an alanine-for-threonine substitution corresponding to position No. 60 of the transthyretin monomer. Detection of the FAP gene in asymptomatic carriers was accomplished by hybrid isoelectric focusing of transthyretin in the presence of dithiothreitol and high concentrations of urea, and by Southern blotting of Pvull-digested leukocyte deoxyribonucleic acid. This type of FAP was found to be identical to the previously described Appalachian amyloid. Patients with FAP and their asymptomatic gene-carrying offspring had significantly reduced levels of serum transthyretin and retinol-binding protein.

Adult↗
PubMed1989

The nucleus pontis centralis caudalis in Huntington's disease.

Slow saccadic eye movements occur in some patients with Huntington's disease (HD), and minor defects of supranuclear eye movement control can be demonstrated in the majority by neuroophthalmological laboratory methods. In the pathogenesis of slowed saccades, a lesion of the paramedian pontine reticular formation and specifically the nucleus pontis centralis caudalis was considered likely due to similar eye movement disturbances in well documented degenerative and vascular lesions of the lower pontine tegmentum. A systematic morphometric study was performed on the nucleus pontis centralis caudalis in 9 patients with HD. Two of them had grossly defective saccades during life, and 7 had normal eye movements on routine examination. In 8 patients, the nucleus was reduced in size, revealed a higher than normal neuronal density, and a striking loss of large neurons. One patient with HD and normal morphometric results had died 2 years after the onset of chorea from an unrelated illness. It is proposed that the nucleus pontis centralis caudalis is regularly affected in HD and that progressive loss of large neurons is the cause of saccadic slowing.

Adult↗
PubMed1988

Familial oculoleptomeningeal amyloidosis. Report of a new family with unusual features.

A family had a dominantly inherited amyloid angiopathy that involved the meninges of the brain and spinal cord, retina, vitreous humor, peripheral nerves, and systemic organs. Clinical features included hemiplegic migraine, periodic obtundation, psychosis, seizures, intracerebral hemorrhage, myelopathy, visual impairment, deafness, and peripheral neuropathy. Pathological findings consisted of amyloid deposition in the leptomeningeal and retinal vessels, in the vitreous humor, and in perivascular tissue throughout the body. Evaluation of the amyloid showed it to be a transthyretin (prealbumin). A brief course of plasmapheresis produced a short-lived decrease concentration in circulating transthyretin.

Adult↗
PubMed1988

Comparative immunocytochemistry of Pelizaeus-Merzbacher disease, the jimpy mouse, and the myelin-deficient rat.

Patients with Pelizaeus-Merzbacher disease (PM), hemizygous mice with the jimpy mutation (jp/Y), and hemizygous rats with X-linked myelin deficiency (md/Y) share a profound lack of proteolipid protein (PLP) in their central nervous systems (CNS). The peripheral nervous system is normal. These X-linked disorders are associated with or actually caused by the lack of normal oligodendrocytes. Vibratome sections of brain were incubated with antisera to myelin basic protein (MBP), myelin-associated glycoprotein (MAG), 2':3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) (EC 3.1.4.37), PLP, a synthetic PLP-peptide, glial fibrillary acidic protein (GFAP), and transferrin. Reaction product was developed by sequential incubation with biotinylated second antibodies, the avidin-biotin-peroxidase complex (ABC), and diaminobenzidine (DAB) plus hydrogen peroxide as chromogenic substrates. In PM, jp/Y and md/Y, islands of myelin-like structures were revealed by antisera to MBP, MAG, and CNP. Reaction product after application of anti-PLP was absent. Reaction product after anti-PLP-peptide was restricted to infrequent bizarre cells possibly representing abnormal oligodendroglia. The lack of oligodendrocytes in jp/Y and md/Y could also be confirmed by immunocytochemistry for transferrin.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1988

Amyloid fibril protein in familial amyloidosis with cranial neuropathy and corneal lattice dystrophy (FAP type IV) is related to transthyretin.

Immunocytochemical methods were used to study the nature of the amyloid deposits in the Finnish type-familial amyloid polyneuropathy (FAP) type IV, which is characterized by cranial neuropathy and corneal lattice dystrophy. Commercial antisera to human plasma transthyretin (prealbumin) did not stain the amyloid deposits, but in every case a positive staining was obtained with antibodies raised against transthyretin-related amyloid fibril whole protein isolated from the myocardium of a patient with familial amyloid polyneuropathy from the state of New York. The FAP type IV amyloid deposits stained also with antiserum to serum amyloid P component, but did not stain with antisera to retinol-binding protein, amyloid A protein, gamma-trace protein, beta 2-microglobulin, or immunoglobulin light chains. The serum level of serum transthyretin was significantly decreased in FAP type IV patients (256 +/- 75 (SD) mg/L, n = 15) as compared with Finnish control subjects (360 +/- 56 mg/L, n = 30, P less than 0.001), whereas the level of retinol-binding protein was within the normal range. The results of this study strongly suggest that the amyloid fibril protein in FAP type IV amyloidosis is related to transthyretin.

Adult↗
PubMed1988

Brain hemosiderin and superficial siderosis of the central nervous system.

Brain tissue from five patients with superficial siderosis of the central nervous system was examined by immunocytochemistry for ferritin, glial fibrillary acidic protein (GFAP), alpha 1-antitrypsin, and alpha 1-antichymotrypsin, and by lectin affinity cytochemistry with biotinylated Ricinus communis agglutinin-1 (RCA-1). The sections were pretreated with 2,2'-dipyridyl and sodium hydrosulfite to remove iron and to reveal the antigenic sites. In siderotic cerebellar cortex, ferritin reaction product occurred in the hemosiderin matrix, the cell bodies and processes of Bergmann glia, and in microglia. Astrocytes other than Bergmann glia did not contain ferritin reaction product. RCA-1 stained microglia and hemosiderin whereas antisera to alpha 1-antitrypsin and alpha 1-antichymotrypsin only reacted with iron-depleted granules. The selective vulnerability of the eighth cranial nerve was explained by the presence of ferritin-reactive and lectin-positive microglia. Hemosiderin isolated from frozen cerebellum contained ferritin, GFAP, and vimentin. The presence of the intermediate filament proteins was likely due to co-localization with hemosiderin granules in Bergmann glia. The ability of the brain to biosynthesize ferritin in response to prolonged contact with hemoglobin iron is thought to be the most important factor in the pathogenesis of superficial siderosis. The great severity of the lesion in the exposed cerebellar cortex is readily explained by accelerated ferritin biosynthesis in Bergmann glia.

Adult↗
PubMed1987

Defective biosynthesis of proteolipid protein in Pelizaeus-Merzbacher disease.

The brain of an 18-year-old patient with Pelizaeus-Merzbacher disease was examined by standard neuropathological and biochemical methods and by immunocytochemical and immunochemical techniques. Analysis revealed a lack of myelin-specific lipids, but showed a residual immunoreactivity for myelin basic protein, myelin-associated glycoprotein, and 2',3'-cyclic nucleotide-3'-phosphodiesterase. Examination by immunocytochemistry and enzyme-linked immunosorbent assay showed an absence of proteolipid apoprotein (lipophilin). The peripheral nervous system was normal. Pelizaeus-Merzbacher disease in humans shares many neuropathological and biochemical features with X-linked mutations in animals, e.g., the jimpy mouse and myelin-deficient rat. The specificity of this protein deficiency in Pelizaeus-Merzbacher disease gains additional support from the recent mapping of the lipophilin gene to the human X chromosome.

Adolescent↗
PubMed1987

Effect of free malonate on the utilization of glutamate by rat brain mitochondria.

Malonate is an effective inhibitor of succinate dehydrogenase in preparations from brain and other organs. This property was reexamined in isolated rat brain mitochondria during incubation with L-glutamate. The biosynthesis of aspartate was determined by a standard spectrofluorometric method and a radiometric technique. The latter was suitable for aspartate assay after very brief incubations of mitochondria with glutamate. At a concentration of 1 mM or higher, malonate totally inhibited aspartate biosynthesis. At 0.2 mM, the inhibitory effect was still present. It is thus possible that the natural concentration of free malonate in adult rat brain of 192 nmol/g wet weight exerts an effect on citric acid cycle reactions in vivo. The inhibition of glutamate utilization by malonate was readily overcome by the addition of malate which provided oxaloacetate for the transamination of glutamate. The reaction was accompanied by the accumulation of 2-oxoglutarate. The metabolism of glutamate was also blocked by inclusion of arsenite and gamma-vinyl-gamma-aminobutyric acid but again added malate allowed transamination to resume. When arsenite and gamma-vinyl-gamma-aminobutyric acid were present, the role of malonate as an inhibitor of malate entry into the mitochondrial interior could be determined without considering the inhibition of succinate dehydrogenase. The apparent Km and Vmax values for uninhibited malate entry were 0.01 mM and 100 nmol/mg protein/min, respectively. Malonate was a competitive inhibitor of malate transport (Ki = 0.75 mM).

Animals↗
PubMed1986

Olivopontocerebellar atrophy: immunocytochemical and Golgi observations.

Brain tissue was obtained promptly after death from a patient with autosomal dominant olivopontocerebellar atrophy and studied by immunocytochemistry and a Golgi technique. Antiglutamic acid decarboxylase showed severe loss of Purkinje cells and their terminals in the dentate nucleus. Stains for neuron-specific enolase (NSE) and microtubule-associated proteins (MAP) confirmed the integrity of the dentate nucleus. Basket and stellate cells revealed secondary changes, but Golgi neurons were intact. Methods for NSE and MAP disclosed dendritic alterations and loss of neurons in the basis pontis and inferior olivary nuclei. Golgi impregnation of Purkinje cells showed loss of major dendrites, paucity of spiny branchlets, and axonal expansions.

Aged↗
PubMed1984

Malonate, malonyl-coenzyme A, and acetyl-coenzyme A in developing rat brain.

Free malonate, malonyl-coenzyme A (malonyl-CoA), and acetyl-CoA were assayed in rat brain at developmental ages from the 20th day of gestation to 60 days of postnatal life. The determination of malonate was based on its conversion to malonyl-CoA and decarboxylation to acetyl-CoA by enzyme extracts from Pseudomonas fluorescens. The resulting acetyl-CoA reacted with [4-14C]oxaloacetate to form [5-14C]citrate, which was isolated by TLC. Malonyl-CoA in perchloric acid extracts from brain was converted to acetyl-CoA by rat liver mitochondrial malonyl-CoA decarboxylase (EC 4.1.1.9). Acetyl-CoA derived from this step was assayed by a modified CoA-cycling procedure. Brain acetyl-CoA was also assayed by CoA cycling. Prenatal brain contained no free malonate but malonyl-CoA was present. The acetyl-CoA level was relatively high just prior to birth and declined slightly with growth. Malonate concentrations after birth rose rapidly to reach 192 nmol/g wet weight at 60 days. Adult levels for malonyl-CoA and acetyl-CoA were 1.83 and 1.90 nmol/g wet weight, respectively. The origin and natural role of free malonate in brain are not known but deacylation of malonyl-CoA by reversal of the malonyl-CoA synthetase reaction is postulated. Rat liver and kidney also contain substantial concentrations of free malonate.

Acetyl Coenzyme A↗
PubMed1982

Fine structure of neurons of the hypertrophied human inferior olive.

Ultrastructural study of hypertrophied inferior olives from three cases of palatal myoclonus revealed tha nerve cells not infrequently contained numerous round, homogeneously electron-dense granules (mean diameter, 360 nm) located within expanded cisternal profiles of rough endoplasmic reticulum (RER). Control tissue did not contain similar structures. These granules may consist of proteinaceous secretion of the RER which, for reason unknown, accumulates during transsynaptic degeneration of the inferior olive. Additional noteworthy electron microscopic features of neurons of the hypertrophied olive were as follows: 1. neurofilamentous hyperplasia, greater in dendrites than in perikarya; 2. vacuoles in intermediate and large (up to 15 mum) size, derived from RER; and 3. prominent intracytoplasmic protrusions by boutons containing dense core vesicles (mean diameter, 98 nm). Glomeruloids were identified ultrastructurally and consisted of numerous boutons interspersed among neurofilament-rich dendrites and occasional, filament-packed astrocytic profiles. Frequently, these boutons also contained dense-core vesicles. It seems possible that the boutons mentioned may arise from collateral axonal sprouts.

Adult↗
PubMed1981

Hereditary ataxia and the sixth chromosome.

Possible linkage of the gene or genes for dominant hereditary ataxia and three genetic markers on the short arm of the sixth chromosome (HLA, properdin factor B [Bf], and glyoxalase I) was investigated in five families. Logarithmic odds (lod scores) were calculated for the linkages and found to be either inconclusive or in favor of nonlinkage. Caution is advised in the summing of lod scores for separate families because of the wide spectrum of clinical and anatomical manifestations of dominant hereditary ataxia. Three families with recessive hereditary ataxia were also studied. Identical haplotypes occurred in affected and unaffected siblings. It did not appear likely that the recessive genes of the parents were transmitted in linkage with the markers on the short arm of the sixth chromosome.

Ataxia↗
PubMed1981

Oligodendroglioma of the medulla oblongata in a neonate.

A 4-month-old boy had recurrent attacks of apnea before progressive quadriparesis, ocular motility disturbance, and depressed corneal reflexes led to the discovery of a posterior fossa mass. Death occurred postoperatively during prolonged apnea. Necropsy disclosed an oligodendroglioma of the medulla oblongata. A review of this rare neoplasm in the neonatal period is given.

Apnea↗