PubMed Health⌕ Search

Biomedical subjects

H von Holst

Publications and source records attributed to H von Holst.

At least 19 recordsLinked to original sources
PubMed2001

Patients with Primary brain tumours have elevated serum titres of antibodies to the myelin glycolipid sulphatide.

Primary and metastatic brain tumours may result in an altered exposure of normal cellular components to the immune system inducing an immune response measurable in autoantibodies. One potential immunogenic molecule is sulphatide, the major acidic glycolipid in myelin. Thirty-eight sera from 31 patients with primary and metastatic brain tumours have, therefore, been analyzed for the presence of antisulphatide antibodies by an ELISA performed on thin layer chromatography plates. Twenty-eight of the thirty-eight sera (74%) showed a positive antibody titre to sulphatide. The antibody titres were significantly higher (p < 0.01) in sera from patients with primary brain tumours than in sera from those with metastases. The study lends support to the possibility that antisulphatide antibodies could contribute to tissue damage and this might facilitate the invasive growth in primary brain tumours by demyelination. However, the pathogenic significance of these autoantibodies remains to be further elucidated.

Adolescent↗
PubMed1999

Expression of the GM1-species, [NeuN]-GM1, in a case of human glioma.

Altered glycosylation is a common feature in tumors of various kind and particular interest has been focused on the expression of tumor-associated gangliosides. We have previously identified some human glioma-associated gangliosides and in this study yet another, not previously described, ganglioside has been isolated. The ganglioside was prepared from human glioma tissue taken at autopsy. The new ganglioside bound cholera-toxin B-subunit and its structure was confirmed by fast atom bombardment-mass spectrometry to be NeuN-GM1 (II3NeuNH2-GgOse4Cer). In the dissected tumor specimen, the concentration of NeuN-GM1 was 0.1 micromol/g wet weight and accounted for approximately 20% of the monosialoganglioside fraction. Normal human brain tissue specimens (n = 10) did not contain detectable (>0.5 nmol/g wet weight of tissue) amounts of NeuN-GM1, indicating that this ganglioside might be associated with human glioma. However, none of the 17 other tumour specimens reveal any detectable amounts of this ganglioside. In conclusion, NeuN GM1 is a glioma-associated ganglioside but its exceptional expression limits its relevance as a molecule involved in general tumor biology.

Brain↗
PubMed1998

An experimental head restraint concept for primary prevention of head and neck injuries in frontal collisions.

The Experimental Head Restraint Concept (EHRC), a 'safety belt' for the head, is designed to reduce forces to the head and neck, in frontal car crashes. The EHRC was evaluated experimentally in frontal collision for a crash severity of 11 m/s, and numerically in frontal collision for a crash severity of 11 and 15 m/s. Experimental data obtained from a frontal barrier test (11 m/s) showed a 67% reduction of the HIC value from 411 (without EHRC) to 136 (with EHRC). The same level of reduction was also obtained for the higher speed in the numerical simulation. The moment in the neck was shown in experimental configuration to increase a few percent using the EHRC, but as presented in a numerical analysis, the moment was reduced by stiffening the EHRC. The EHRC clearly has a potential role in the search for primary prevention of neurotrauma injuries in frontal related car crashes. However, there is a strong need for more advanced injury criteria for the neck in order to optimize such complex safety systems.

Accidents, Traffic↗
PubMed1997

The presence of foetal ganglioside antigens 3'-isoLM1 and 3'6'-isoLD1 in both glioma tissue and surrounding areas from human brain.

Glioma-associated gangliosides, in particular the expression of foetal gangliosides 3'-isoLM1 and 3'6'-isoLD1, have been investigated in biopsies from 44 patients with astrocytoma grade II, anaplastic astrocytoma, anaplastic oligodendrogliomas, oligodendrogliomas, and glioblastoma multiforme. The total ganglioside content decreased in proportion to the estimated number of tumour cells present in the biopsy. Ganglioside GD3 was increased in 17 of the tumour tissues and in 6 of the surrounding area specimens. In agreement with our previous studies, tumour specimens contained the lactoseries ganglioside 3'-isoLM1 and, as demonstrated for the first time, the disialylated form of the ganglioside, 3'6'-isoLD1. These gangliosides are in normal brain tissue restricted to the developmental period. Most frequent was the expression of ganglioside 3'-isoLM1 which was detected in 92% of the tumour specimens in concentrations varying between just detectable amounts to 13 nmol/g wet weight. In the area surrounding the macroscopic tumour tissue 78% of the specimens expressed 3'-isoLM1 and the values varied between just detectable amounts to 24 nmol/g wet weight. Ganglioside 3'6'-isoLD1 was found in 47% of the tumour biopsies and in only 17% of the specimens taken outside macroscopic tumour tissue. The values varied between non-detectable amounts to 40 nmol/g wet weight of tissue. The expression of 3'-isoLM1 correlated significantly (p < 0.01) to malignancy grade. For 3'6'-isoLD1 a significant (p < 0.05) difference was found between tumour and surrounding tissue. Likewise, 3'6'-isoLD1 correlated significantly (p < 0.05) to malignancy grade. The correlation between 3'-isoLM1 and 3'6'-isoLD1 to malignancy grade and the frequent expression of these gangliosides both in the tumour itself and in its surrounding area should encourage additional studies concerning their biological role in tumour disease.

Adolescent↗
PubMed1997

Increased activity of lysosomal glycohydrolases in glioma tissue and surrounding areas from human brain.

Increased metabolic activity represented by an increase in both anabolism and catabolism in tumours, including gliomas, is a well known phenomenon and utilised in positron emission tomography imaging of tumours. In this study lysosomal enzyme activities of some glycohydrolases were investigated in glioma tissue from human brain. Tumour tissue (ten cases) and brain tissue surrounding the tumour tissue (seven cases) from patients with a histopathological diagnosis of glioblastoma multiforme or anaplastic astrocytoma were analysed for activity of the lysosomal enzymes galactosylceramidase, glucosylceramidase, beta-galactosidase, beta-N-acetyl-glucosaminidase, beta-glucuronidase and acid phosphatase. All of the investigated lysosomal enzymes except galactosylceramidase showed increased activity compared with that in normal brain tissue. Moreover, despite sparsity of tumour cells the specimens taken from surrounding areas showed elevated activities of the same enzymes. The findings indicate an upregulation of the activity not only in tumour but also in normal cells of the surrounding area.

Adolescent↗
PubMed1997

Serious brain injury from traffic-related causes: priorities for primary prevention.

This study evaluated the incidence and outcome of serious brain injury from traffic-related causes in 695 patients admitted to the Department of Neurosurgery at Karolinska Hospital during 1981-1992. A total of 37.3% of patients were car occupants, 28.1% pedestrians, 12.9% bicyclists, 12.2% car-bicycle/car-moped and 9.5% motorcycle riders. The dominating injury was brain contusion (61.6%) verified with computerized tomography. The level of consciousness was evaluated by the Glasgow Coma Scale (GCS) and outcome by the Glasgow Outcome Scale (GOS) at discharge and 6-36 months thereafter. The final outcome was 67.5% good recovery (GOS 4-5), 11.5% severely disabled (GOS 2-3) and 21.0% GOS 1 or brain dead. Patients with GOS < 4 (32.5%) were severely disabled and motivate priorities for injury prevention. Car occupants represent 40.7% of the total, followed by pedestrians at 33.6% and bicyclists at 18.2%. Much remains to be done in the primary prevention of disabling brain injury to car occupants and pedestrians. In order to achieve a more-effective primary prevention, future research should be directed toward biomechanical aspects of brain contusion as a dominating brain injury.

Accidents, Traffic↗
PubMed1997

Increased levels of cholesterol esters in glioma tissue and surrounding areas of human brain.

The proliferation of glioma cells requires cholesterol, which could be provided by synthesis within the cells or by uptake of cholesterol esters in particles of Low Density Lipoprotein (LDL). Cholesterol esters and cholesterol were therefore analysed in human glioma tissue, its surrounding areas and serum from 40 patients. The analyses revealed an increased concentration of cholesterol esters up to 100 times (0.1-10 mumol/g) in both tumour-tissue and surrounding areas compared with control material (< 0.1 mumol/g). The analyses also demonstrated that cholesterol esters in tumour tissue eminated mainly from serum. The cholesterol concentrations were significantly lower in tumour tissue compared with surrounding areas as expected. These results indicate that tumour cell proliferation utilises serum derived cholesterol esters presumably carried by LDL particles.

Adolescent↗
PubMed1996

Increase of insulin-like growth factor (IGF)-1, IGF binding protein-2 and -4 mRNAs following cerebral contusion.

The insulin-like growth factor (IGF) system has a role in repair following hypoxic-ischemic injury in many tissues including the brain. To study the involvement of the IGF system following head trauma, we used a rat contusion model, which produces a focal lesion of the cerebral cortex. Molecules in the IGF system were analyzed using in situ hybridization at different times following impact. We observed a dramatic up-regulation of insulin-like growth factor binding protein-2 (IGFBP-2) mRNA in cortical areas adjacent to the injury 24 h after impact, with a peak 10-fold increase engaging most of the ipsilateral cortex 2 and 3 days post-contusion. Seven days after the contusion, IGFBP-2 expression was only moderately up-regulated and again concentrated around the injury. IGFBP-4 mRNA levels increased 4-fold ipsilateral to the site of injury, with retained pattern of cortical expression. IGFBP-3, IGFBP-5 and IGFBP-6 mRNA all displayed distinct expression patterns in the brain but no significant changes were observed following injury. In contrast, IGF-1 mRNA levels were very low prior to contusion, but increased markedly at the site of injury with a peak at day 3. We were unable to detect any changes in the type 1 IGF-receptor or IGF-2 mRNA following contusion. The neuropeptide cholecystokinin (CCK) mRNA was clearly up-regulated following contusion, with an even distribution over the ipsilateral cortex. The expression pattern of molecules in the IGF system post-contusion differs in part to changes observed following hypoxic-ischemia or ischemia alone, perhaps reflecting different regulatory mechanisms depending on the type of injury.

Animals↗
PubMed1996

Activation of the complement cascade and increase of clusterin in the brain following a cortical contusion in the adult rat.

The aim of the present study was to examine the glial cell response and the possible involvement of the complement cascade following a cerebral cortical contusion. The lesion was produced using a standardized weight-drop technique in adult rats. The blood-brain barrier was damaged, as demonstrated by a decrease of immunoreactivity for a tight junction protein normally expressed by endothelial cells of small vessels in the central nervous system. Increased immunoreactivity for microglial (OX42) and astroglial cells (glial fibrillary acidic protein), as well as macrophages expressing ED1-immunoreactivity (IR) were found in the vicinity of the lesion at all postoperative survival times (2-14 days). In the present study complement factor C3d- and C9-IR was found around the lesion, indicating that activation of the complement cascade had taken place. Furthermore, immunoreactivity for the putative complement inhibitor clusterin (sulfated glycoprotein-2) was found in some of the injured neurons. The contralateral hemisphere showed no evidence of the reaction found in the ipsilateral hemisphere. The balance between complement activation and complement inhibitors may have an impact on the degenerative components in the brain following traumatic injury and in particular on the events leading to nerve cell death.

Animals↗
PubMed1995

Outcome of head injury in 2298 patients treated in a single clinic during a 21-year period.

Between 1968 and 1988, 2298 head-injured patients of all grades of severity were registered in the data bank of a single clinic. The majority of patients were admitted to a community hospital and transferred later to the neurosurgical clinic. The data included mechanism of injury and clinical status at admission, including the level of consciousness according to the Glasgow Coma Score (GCS) before and after resuscitation. After admission, nearly all patients below a score of 8 were intubated and treated with controlled ventilation until the patient awakened, died, or had remained in a steady state for approximately 3 weeks. Assessment of the final outcome was made according to the Glasgow Outcome Scale (GOS) both at discharge and again after the patient's status was stabilized. The results show a stable yearly outcome during the 21 years of recording but a significantly improved good recovery and mortality rate when compared with our previous results. Outcome was significantly correlated to age and type and severity of lesion, as judged by the postresuscitation GCS. The outcome of the 1264 most severely injured, comatose patients (GCS < 9) shows a good recovery rate of 55%, a severely disabled rate of 14%, a vegetative rate of 7%, and a mortality rate of 24%. We attribute these results, which compare favorably with others, to prompt airway control and controlled ventilation in unconscious patients.

Accidental Falls↗
PubMed1995

Intracranial traumatic and non-traumatic haemorrhagic complications of warfarin treatment.

An increased referral of patients with anticoagulation related haemorrhages necessitated an analysis of causes and outcome of these complications in a patient group that reflected Swedish therapeutic traditions of anticoagulation treatment. Prospectively, all patients from Stockholm evaluated for warfarin related intracranial haemorrhage occurring during 1987 were analysed and their 6 month outcome recorded. Sixty-eight patients were included. The results of intracranial haemorrhagic complications were catastrophic with a 77% mortality rate. Their incidence was much higher than expected. Forty-one patients had non-traumatic intracerebral haematomas, 1 had a non-traumatic subarachnoid haemorrhage and 26 had traumatic injuries. In the 42 patients with non-traumatic haemorrhages, the indications for anticoagulation were cerebral ischaemic events in a majority (27/42). The remaining 15 patients had different indications for anticoagulation. They also had an increased frequency of hypertension (p < 0.05). In the 26 patients with traumatic haematomas, only 6/26 patients had previous cerebral ischaemic injuries (p < 0.01). Valvular heart prosthesis was their most common indication (11/26) for anticoagulation. Caution in instituting anticoagulation therapy in patients with hypertension or cerebrovascular disease, which is an important indication for anticoagulation in Sweden, is mandatory. Adherence to strict treatment regimens and their continuous reevaluation may help to avoid complications. The finding of more patients than expected with haemorrhagic complications is not compatible with the risk evaluations used to justify anticoagulation therapy in the patient groups studied. Clinical practice must have changed with time, showing that risk evaluations from controlled trials or retrospectively collected clinical data from selected patients are not necessarily applicable for long-term clinical practice.

Adult↗
PubMed1993

Intracranial infusion of purified nerve growth factor to an Alzheimer patient: the first attempt of a possible future treatment strategy.

We report on the clinical outcome of a first case of intracranial infusion of nerve growth factor (NGF) to an Alzheimer patient. The therapeutic attempt is based on animal research showing that NGF stimulates central cholinergic neurons of the type known to be lost during the development of Alzheimer's disease (AD). Furthermore, our own previous clinical experience of infusing NGF to support the survival of intracranially transplanted adrenal chromaffin cells to Parkinsonian patients indicate this approach to be technically possible and safe and clinically of significant potential. Our first case was a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF over three months resulted in a marked transient increase in uptake and binding of [11C]nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF infusion, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects of the NGF infusion were found. The results of this single case indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.

Aged↗
PubMed1993

Characterization of insulin-like growth factor 1 in human primary brain tumors.

Insulin-like growth factor 1 (IGF-1) is involved in the regulation of brain development and has been suggested as an autocrine stimulator of brain tumor cell proliferation. This study demonstrates the expression of IGF-1 in tumor tissue from human gliomas and one esthesioneuroblastoma. Using immunohistochemistry, expression of an IGF-1-like peptide was localized in tumor cells of 6 of the 9 gliomas examined as well as the esthesioneuroblastoma. From one anaplastic oligodendroglioma (which showed strong IGF-1 immunostaining) the IGF-1 transcripts were characterized after isolation of mRNA followed by amplification using the reverse transcriptase-polymerase chain reaction. Two IGF-1 complementary DNAs resulting from alternative splicing of the IGF-1 primary transcript were identified. These transcripts encode two different precursor proteins which correspond to Ea IGF-1 and Eb IGF-1. The significance of IGF-1 alternative mRNA splicing pathways remains to be determined.

Amino Acid Sequence↗
PubMed1993

Synthesis of [1-11C]D-glucosamine and evaluation of its in vivo distribution in rat with PET.

D-Glucosamine is a structural unit of many biologically interesting macromolecules. To investigate the feasibility of using labelled D-glucosamine as a tracer for anabolic processes, a two-step synthetic procedure for specifically labelling D-glucosamine in position 1 with carbon-11 was developed. [11C]Cyanide was reacted with an imine precursor, N-benzyl-D-arabinosylamine, to generate the [1-11]alpha-amino nitrile. Reduction to [1-11C]D-glucosamine was accomplished by catalytic hydrogenation using PdCl2 and the N-benzyl group was simultaneously removed. The total synthesis time from end-of-trapping of [11C]cyanide was 40-45 min and the decay-corrected radiochemical yield was 5-10% after HPLC isolation. The biodistribution of [1-11C]D-glucosamine in rat following i.v. bolus injection was investigated using positron emission tomography and showed that the availability of this substance for CNS anabolism is low with the primary limitation being the intact blood-brain barrier.

Animals↗
PubMed1993

Expression of gangliosides GD3 and 3'-isoLM1 in autopsy brains from patients with malignant tumors.

Three autopsy brains from patients who succumbed to malignant gliomas have been analyzed in various regions with regard to their ganglioside content. The study focused on the gangliosides GD3 and 3'-isoLM1, which in a previous study of biopsies were found to be associated with these tumors. In particular, 3'-isoLM1, was suggested to be a marker for malignant gliomas. The highest concentrations (200-1,000 nmol of sialic acid/g wet weight) of GD3 was found in specimens of macroscopically pure tumor, where the proportion of GD3 was, at the most, 78% (range, 11-78%) of the total ganglioside sialic acid compared with < 10% in normal brain tissue. The proportion of the total ganglioside sialic acid made up by GD3 was also elevated in the periphery of the tumor and in the same region in the opposite hemisphere, where no tumor cells were detected. In four of eight brain metastases of various carcinomas, GD3 was > 10% of the total ganglioside sialic acid (range, 3-37%). The ganglioside 3'-isoLM1, as determined by TLC-enzyme-linked immunosorbent assay using a specific monoclonal antibody (SL-50), was not present at detectable levels in any of the macroscopically homogenous tumor areas. It was, however, found in the periphery of the tumor, in the corpus callosum, and at highest concentrations in the region of the opposite hemisphere corresponding to the tumor. The concentration varied between 0.1 and 6.0 nmol/g wet weight of tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage.

Serum and cerebrospinal fluid (CSF) samples from 12 patients were analyzed for interleukin (IL)-6, soluble IL-2 receptor (IL-2R), and soluble CD8 levels in order to determine the immune activation profile following subarachnoid hemorrhage (SAH). Dramatically increased levels of IL-6 and moderate increases of soluble IL-2R were detected in the CSF in 11 of the 12 patients; slightly elevated levels of soluble CD8 were observed in six patients. The IL-6 levels were higher on Day 6 than on Days 3 and 9. The increases in IL-6, soluble IL-2R, and soluble CD8 levels in the CSF samples were not paralleled by increased values in the serum samples, and thus probably reflected an intrathecal synthesis of the cytokine. Passive transfer of IL-6 across the blood-brain barrier seemed not to occur since the serum and CSF levels of IL-6 showed a negative correlation. The findings suggest a severe inflammatory affection of the central nervous system that could be of importance in understanding the clinical course in patients following SAH.

Adult↗
PubMed1993

High recurrence rate following aspiration of colloid cysts in the third ventricle.

Sixteen patients treated between 1969 and 1989 for a colloid cyst of the foramen of Monro by stereotactically guided aspiration (not stereotactic extirpation) were evaluated to assess the long-term outcome of the procedure. Thirteen of these patients required reoperation due to an acute comatose state, failure to achieve permanent reduction of the cyst, or symptomatic hydrocephalus. Of these 13, six were treated twice and two were treated three times by stereotactic aspiration. Five patients underwent microsurgical extirpation and three had a shunt placed following a failed aspiration. Failure of the first procedure was detected within the first 2 months after treatment in eight patients and after more than 6 years in seven. Following stereotactic aspiration, three patients experienced a temporary memory deficit and confusion and one patient suffered a central pain syndrome. Eleven of the 26 procedures were followed by a recurrence 6 to 15 years after treatment; seven recurrent cysts were detected after more than 8 years. Of the patients with recurrences, three did not undergo repeat surgery but showed an increase in cyst size at the latest follow-up examination. It is suggested that radical removal by open or stereotactically guided microsurgery is the method of choice since stereotactic aspiration fails to offer a radical or permanent treatment for colloid cysts of the third ventricle.

Adolescent↗