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Biomedical subjects

L Gerhard

Publications and source records attributed to L Gerhard.

At least 19 recordsLinked to original sources

The expression of nerve growth factor receptor on Schwann cells and the effect of these cells on the regeneration of axons in traumatically injured human spinal cord.

To investigate the effects of Schwann cells and nerve growth factor receptor (NGFR) on the regeneration of axons, autopsy specimens of spinal cord from 21 patients with a survival time of 2 h to 54 years after spinal cord trauma were studied using immunohistochemistry and electron microscopy. Regenerating sprouts of axons could be observed as early as 4 days after trauma. At 4.5 months after trauma, many regenerating nests of axons appeared in the injured spinal cord. The regeneration nests contained directionally arranged axons and Schwann cells. Some axons were myelinated. In injured levels of the spinal cord, the Schwann cells exhibited an increased expression of NGFR within spinal roots. These results show that an active regeneration process occurs in traumatically injured human spinal cord. The NGFR expressed on Schwann cells could mediate NGF to support and induce the axon regeneration in the central nervous system.

Adolescent

Neuronal ceroid-lipofuscinosis--late-infantile or Jansky-Bielschowsky type--revisited.

The tissues from three patients with late-infantile NCL originally described by Max Bielschowsky became available to apply modern techniques such as fluorescence microscopy, electron microscopy and immunohistochemistry. While regular tinctorial preparations of the tissues documented a neuronal storage disorder in all three patients' tissues, the accumulated material proved to be autofluorescent, showed the ultrastructure of curvilinear lipopigments, and reacted strongly with an antibody against the subunit-C of mitochondrial ATP synthase, a major component of lipopigments in NCL and also with an antibody against sphingolipid activator proteins. Thus, these modern morphological techniques demonstrated that the originally described three siblings with late-infantile "amaurotic familial idiocy" really had neuronal ceroid-lipofuscinosis of the late-infantile or Jansky-Bielschowsky type, according to current diagnostic criteria. This type of archival study may also contribute to the mosaic of medical history.

Brain

[Optical and tactile hallucinosis as clinical onset of Creutzfeld-Jakob disease].

A patient suffering from Creutzfeld-Jakob disease (CJD) complained of optical hallucinations, followed by feelings of persecution. Clinical, encephalographic and neuropathological findings pointed towards a focalized beginning of the disease process in the right frontal and temporal lobe. The hypothesized further spread of the infectious agent, as indicated by electroencephalographic and neuropathological findings, was accompanied by periacute manifestation of dementia and an irreversible disturbance of vigilance. The diagnosis of CJE can be especially difficult in the early stages of the disease, with dementia, myocloni and typical electroencephalographic findings still absent.

Aged

Reexpression of nerve growth factor receptor in human traumatic injured spinal cord.

In this study, the reexpression of nerve growth factor receptor (NGFR) on paraffin sections of the human spinal cord was examined with immunohistochemical method in 18 cases with survival periods of 2 hours to 28 months after trauma. The results were as follow: the reexpression of NGFR in motoneurons of the ventral horn began on the fourth day after trauma and decreased within 30 days after trauma. However, it could still be observed in patients who survived up to 28 months. The axons in funiculus dorsalis reexpressed NGFR 7 hours to 9 weeks after injury, which may be interpreted as axoplasmic transport effect of NGFR in the spinal ganglion cells. NGFR labelled intraspinal microvessels were present in the injured spinal cord. Reexpression of NGFR in motoneurons after injury reflects an increased demand of neurotrophic factors, and an increased access exerting the physiological effects of trophic factors mediated by NGFR.

Adolescent

Operative treatment and prognosis of syringomyelia.

Twenty-two patients suffering from syringomyelia were treated operatively. Different shunt procedures were performed. Most often syringo-subarachnoid shunt (seven cases) and syringopleural shunt (eight cases) were used. Operative findings and complications were discussed. Postoperative improvement was observed in five patients, twelve were stable-unchanged, four showed further deterioration and one died. Operative treatment should be performed before gross neurological deficit is established.

Adolescent

Intravascular lymphomatosis of the CNS: clinicopathologic study and search for expression of oncoproteins and Epstein-Barr virus.

Five cases of intravascular lymphomatosis (IVL) are reported. Diffuse or focal cerebral signs suggestive of vascular disease occurred in four cases, but case 5 presented with symptoms similar to Creutzfeld-Jakob disease. Clinical course ranged from two to eight months and diagnosis was made in all cases by autopsy. Neoplastic lymphoid cells mainly lodged in lumina of small vessels in many organs, but infarction was confined to the CNS. Some extravascular tumor cells were regularly seen. All cases corresponded to high-grade Non-Hodgkin lymphomas of B-cell type and displayed high proliferation indices. Different from findings in primary cerebral and nodal lymphomas, neither p53 nor bcl-2 oncoproteins were detectable. Absence of EBV genome and EBV latent membrane protein from IVL was demonstrated for the first time.

Aged

A Golgi study on the red nucleus in man.

The different cell types comprising the human red nucleus (RN) from eight patients without neuronal diseases were investigated using the Golgi-Braitenberg method for long-stored autopsy material. No giant cells were found due to regression of the magnicellular part of the human RN. We found larger (40-50 microns) and smaller (30 microns perikaryon size) medium-sized multipolar neurons with long dendrites, mushroom spines and typical distal dendritic tufts. The larger medium-sized RN neurons had some brush-shaped dendritic end portions which could not be observed in the Golgi studies on various other mammals described in the literature. We additionally found small neurons with a perikaryon size of 15 microns. These cells were thought to be intrinsic neurons similar to those in animal investigations. The neuronal types found in the normal human RN corresponded to those in the parvicellular part of the mammalian RN. Dendritic end brushes, however, are typical only for the human RN.

Aged

A Golgi study of human locus coeruleus in normal brains and in Parkinson's disease.

The locus coeruleus (LC) of eight adults without neurodegenerative disease and eight patients with Parkinson's disease was investigated by means of the Golgi-Braitenberg method for formalin-fixed human autopsy material. As with Golgi studies in the rat and cat, two main neuronal classes could be demonstrated in the human LC: (i) medium-sized fusiform and multipolar LC neurons known to contain neuromelanin and (ii) smaller neurons of widely varying somatic shape and dendritic arborization which are considered to be intermingled neurons of adjacent brain stem nuclei not containing neuromelanin. In Parkinson's disease, the Golgi-impregnated medium-sized LC neurons were reduced in number. They showed marked reduction of dendritic length, severe loss of spines, dendritic varicosities and swollen perikarya. The last two findings could be due in part to Lewy-body inclusions. The smaller non-noradrenergic neurons did not show severe pathological changes by the Golgi impregnation technique, which is in line with the fact that only neuromelanin-containing LC neurons are affected in the pathological process of Parkinson's disease.

Aged

Clinical and cerebral blood flow studies in patients with intracranial hemorrhage and amyloid angiopathy typical of Alzheimer's disease.

Spontaneous intracerebral hemorrhages can occur in patients with severe amyloid angiopathy and other morphological signs of Alzheimer's disease (AD). We observed 15 patients in whom histological examination of brain tissue specimens obtained at surgery revealed characteristic congophilic amyloid deposits in subcortical arteries and/or nerve cells. Clinical follow-up examinations were carried out up to 9 years after diagnosis. In addition, three survivors from the operated group were investigated by neuropsychological testing and single photon emission computer tomography (SPECT) using Tc-99m-HMPAO for determination of regional cerebral blood flow (rCBF). SPECT could not differentiate between the "typical Alzheimer disease pattern" of bilateral temporo-parietal rCBF reduction and flow deficits resulting from previous hemorrhage. Intellectual functioning was found to be impaired to various degrees ranging from normal function to severe dementia (MMS test scores varied between 15 and 26 points); again, it was difficult to differentiate clinically between the nosologic entities mentioned above. On the basis of our present experience we cannot distinguish between brain dysfunction due to Alzheimer's disease and intracranial hemorrhage from amyloid angiopathy. This supports the idea that intracranial hemorrhage may only be one clinical manifestation of amyloid deposits, another one being "Alzheimer's disease" with varying preponderance.

Activities of Daily Living

Brain-restricted amyloidoma of immunoglobulin lambda-light chain origin clinically resembling multiple sclerosis.

Cerebral amyloid deposits restricted to the white matter and associated with intracerebral lymphoma were biochemically identified. The patient died at 58 years of age after 37 years of illness with progressive neurological symptoms clinically indicative of multiple sclerosis. Pathomorphologically, spongiform alteration and demyelinization of the white matter in the vicinity of the amyloid deposits was detected and systemic amyloidosis excluded. Immunohistochemically, the amyloid was found to be of immunoglobulin lambda-light chain origin. To establish the nature of this amyloid, its fibrils were extracted and the amyloid fibril proteins isolated by size exclusion chromatography. Immunochemically, the purified amyloid fibril proteins were shown to be of immunoglobulin lambda-light chain origin. This finding was substantiated chemically. Since the N-terminal amino acid was blocked, tryptic peptides were isolated by reversed phase HPLC. The amino-acid sequence of two major peptides revealed homology with the variable region of the immunoglobulin lambda-light chain. This report defines a novel local A lambda-amyloid disease restricted to the white matter of the brain.

Amyloid

Pathological changes in dendrites of substantia nigra neurons in Parkinson's disease: a Golgi study.

Neurons of the substantia nigra show severe morphological changes in Parkinson's disease. Pathological alterations of cell bodies have been described, whereas those of neuronal processes have hardly been investigated. Golgi impregnation has been the chosen method for demonstrating neuronal processes and dendritic and somatic spines. We therefore used the Golgi-Braitenberg method to qualitatively and semi-quantitatively study the substantia nigra of eight patients with Parkinson's disease compared with eight control cases. Golgi impregnation of substantia nigra neurons was good in all control cases. In full agreement with the analysis of Braak and Braak (1986) three neuronal types within the substantia nigra were found. In cases of Parkinson's disease, severe pathological changes such as decrease of dendritic length, loss of dendritic spines and several types of dendritic varicosities were found only in the melanin-containing pars compacta neurons. Pars reticulata nerve cells were intact. These findings support the predominant role played by the dopaminergic efferent pathway in the degenerative process. The afferent pathway was not affected. This suggests that the substantia nigra lesion is primary in Parkinson's disease. Loss of neurons found in H & E sections corresponded to a lesser amount of impregnated pars compacta neurons in cases with Parkinson's disease when compared to controls. Evidences exist that the duration of the disease may be related to the extent of pathologically altered Golgi-impregnated pars compacta cells. The amount of Lewy bodies in H & E sections corresponded to the quantity of round varicosities in impregnated pars compacta neurons. These round dendritic varicosities were considered to be Lewy body inclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Mycoses of the central nervous system].

The incidence of mycotic infections in the CNS has increased even outside those groups of patients with increased risk (AIDS, drug-addicts, etc.). These cases are secondary complications of other basic diseases favored by the influence of modern drug treatment and misinterpretation of modern diagnostic findings (radiology). A more frequent control of mycotic infections even in routine controls of chronic inflammations and a cautious individual handling of drugs (immunosuppressives, antibiotics, irradiation) should help to avoid these mainly lethal diseases.

Adult

[Syringomyelia from the neurosurgical viewpoint].

Indications for, and methods of, surgical treatment in patients with syringomyelia are described. In 16 patients a syringomyelic cavity was drained. Clinical, radiological and operative findings and results are reported and discussed. In six of twelve patients followed up, progressive deterioration was arrested by operation and two patients improved.

Adolescent

Neuritis cordis due to the acute polyneuritis of the Guillain-Barré syndrome.

Three patients with the Guillain-Barré syndrome which followed the course of Landry's acute ascending paralysis died a sudden cardiac death. Autonomic dysfunction had appeared clinically, consisting of sphincter disturbances in one patient and fluctuating blood pressure and bradycardia in the other. In a twenty-three year old female patient cardiac function had been inconspicuous, apart from tachycardia, but the ECG showed S-T segment depression and flat T waves. Postmortem examination revealed acute inflammatory demyelinating polyradiculoneuritis involving the peripheral autonomic nervous system and especially the nerves of the heart. Immunohistochemically, the inflammatory cell infiltrations of this neuritis cordis consisted of macrophages (MAC 387 positive) and T lymphocytes (UCHL1 positive). No indication of a direct viral infection of the inflamed cardiac nerves was detectable by immunohistochemistry (HSV, CMV, influenza virus) nor by electron microscopy. The neuritis cordis was classified as an inflammatory cardio-neuropathy secondary to a patchy acute polyneuritis of the Guillain-Barré syndrome, involving the autonomic nervous system. Myocarditis could be discounted, and the neuritis cordis was thought to be responsible for the sudden cardiac death.

Acute Disease

Preliminary experimental results with the nitrosourea derivative ACNU in the treatment of malignant gliomas.

Comparative studies were carried out to evaluate the cytotoxic effectiveness of the nitrosureas ACNU (Nimustine) and BCNU (Carmustine) at equitoxic dose levels in xenografts from two astrocytomas grades III/IV (Li, Re) and one oligodendroglioma grade III (Oe) on nude mice. Growth delay was measured as the endpoint. All tumours were characterized initially and at regular intervals in later passages as to their histomorphologic pattern, expression of glial fibrillary acid protein and DNA-content by means of flow cytometry. These characteristics were shown to be unchanged in our xenografts over more than 27 passages. Growth delays of 18.7 days (ACNU) and 2.4 days (BCNU) for the Li-xenograft (p less than 0.01) were observed at an LD10 for both drugs. For the Re- and Oe-xenografts, growth delays of 18.0 vs. 14.0 days (p less than 0.001) and greater than 27.0 vs. 14.2 days (p less than 0.02) were observed at an equitoxic dose of 33 mg/kg ACNU or BCNU i.p., respectively. These preclinical data suggest a therapeutic advantage with ACNU for these high grade gliomas and should encourage further experimental and clinical investigations.

Animals