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Biomedical subjects

A Probst

Publications and source records attributed to A Probst.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Anatomic characteristics pf the elbow joint of the cheetah (Acinonyx jubatus)].

Anatomical structures of elbow joints of six cheetahs were examined by dissection, corrosion casts and radiography. As a result, it was observed that the distal end of humerus is divided into the trochlea humeri for articulation with the ulna and the capitulum humeri for articulation with the radius. As the trochlea humeri is posed oblique and looks like a disc-shaped cone sector, flexion. Flexion of elbow joint is always combined with adduction of the distal parts of the limb, and, respectively, extension with abduction. The cylindrical but also in sagittal direction convex capitulum humeri enables the head of the radius all movements on a spheric sector. Furthermore, advantageous preconditions for rotation in the proximal radioulnar joint are the mighty medical coronoid process, the displacement of the radial tuberosity to the caudal surface of the radius and the insertion of the biceps brachii muscle exclusively on this elevation of the radius. Limiting factors are the insertions of collateral ligaments at the antebrachial skeleton. The lateral collateral ligament inserts only on the radius, the medial collateral ligament mainly on the ulna. The radial anular ligament directly connects the two coronoid processes of the ulna and moreover is intracapsular. The joint capsule is common for both the cubital and the proximal radioulnar joint and five pouches could be described. These were between the lateral epicondyle of humerus and the olecranon, underneath the tendon of origin of the extensor carpi ulnaris muscle, cranially in the bend of the elbow joint, between the head of the radius and the tendon of origin of supinator muscle and the lateral part of radial anular ligament, just as between the medial epicondyle of humerus and the tendons of origin of flexor muscles of the forearm.

Acinonyx↗
PubMed1998

Histological markers in nasal mucosa of patients with Alzheimer's disease.

Neuropathological changes such as dystrophic neurites and the presence of abnormal tau protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer's disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of tau or beta-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated. In these severe cases, tau immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and tau pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease.

Aged↗
PubMed1998

Primary progressive aphasia with glial cytoplasmic inclusions.

We report a 80-year-old woman who suffered from primary progressive aphasia for 3 years. Cranial CT and MRI studies showed moderate cerebral atrophy, more marked in the left frontal and temporal lobes, and SPECT brain scans revealed marked hypometabolism in the left frontal and temporal lobes. Neuropathologic examination of a temporal lobe biopsy demonstrated Gallyas-positive intracytoplasmic inclusions looking like fibrillary tangles and of Gallyas-positive cell processes, probably from glial cells. Glial intracytoplasmic inclusions were immunolabelled with antibodies to ubiquitin and with phosphorylion-dependent antitau antibodies, indicating the presence of hyperphosphorylated tau in the inclusions. There was only mild pathology of cortical neurons consisting in rare perikarya diffusely stained with antitau antibodies. There were no senile plaques, neurofibrillary tangles, 'achromatic' neurons, ballooned cells, Pick or Lewy bodies, nor microvacuoles or spongiform changes of the neuropil. The glial intracytoplasmic inclusions found in this case were similar to those found in multiple system atrophy, and differ from the cortical changes hitherto reported in primary progressive aphasia.

Aged↗
PubMed1997

Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology.

Mutations in the amyloid precursor protein (APP) gene cause early-onset familial Alzheimer disease (AD) by affecting the formation of the amyloid beta (A beta) peptide, the major constituent of AD plaques. We expressed human APP751 containing these mutations in the brains of transgenic mice. Two transgenic mouse lines develop pathological features reminiscent of AD. The degree of pathology depends on expression levels and specific mutations. A 2-fold overexpression of human APP with the Swedish double mutation at positions 670/671 combined with the V717I mutation causes A beta deposition in neocortex and hippocampus of 18-month-old transgenic mice. The deposits are mostly of the diffuse type; however, some congophilic plaques can be detected. In mice with 7-fold overexpression of human APP harboring the Swedish mutation alone, typical plaques appear at 6 months, which increase with age and are Congo Red-positive at first detection. These congophilic plaques are accompanied by neuritic changes and dystrophic cholinergic fibers. Furthermore, inflammatory processes indicated by a massive glial reaction are apparent. Most notably, plaques are immunoreactive for hyperphosphorylated tau, reminiscent of early tau pathology. The immunoreactivity is exclusively found in congophilic senile plaques of both lines. In the higher expressing line, elevated tau phosphorylation can be demonstrated biochemically in 6-month-old animals and increases with age. These mice resemble major features of AD pathology and suggest a central role of A beta in the pathogenesis of the disease.

Alzheimer Disease↗
PubMed1997

Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas.

We analyzed the biodistribution of the 111In-labelled murine anti-tenascin-C MAb BC-2 after intralesional injection in 15 glioblastoma patients. The activated ligand DTPA was conjugated via the isothiocyanato-benzyl group onto BC-2. Conjugates were labelled with 111In, displaying immunoreactivity greater than 90% and labelling efficiency of 99 +/- 1%. In contrast to i.v. injections, excellent tumor uptake was obtained by direct intralesional injection of conjugates that showed only slow systemic release. In serum, conjugates were found to be intact; in urine, only low-molecular-weight decay products were detected. In 8 patients, outflow from the site of injection into systemic circulation was low; daily activity in the serum and urine was found to be below 2% of the total injected radioactivity; most of the injected activity was retained within the tumor, resulting in effective half-lives of 58 +/- 5 hr. In contrast, higher outflow up to 10% of regionally injected 111In-DTPA-BC-2 MAb into systemic circulation resulted in considerable shortening of the effective half-lives to 20 to 40 hr in 7 patients. This outflow was found to correlate with tumor size and blood/brain barrier disruption. In one patient, HPLC analysis of tumor cyst fluid 3 and 6 days after intralesional injection revealed conjugates to be intact and allowed the estimate of about 70% of the total injected 111In-DTPA-BC-2 to be confined to tumor tissue. We conclude that different outflow patterns can be observed following locoregional injection of 111In-DTPA-BC-2, leading to considerable variations in the effective half-lives of isotopes within the tumor, requiring adjustment of the radiation dose in therapeutic trials.

Aged↗
PubMed1997

Pharmacological characterisation of human cerebral cortex somatostatin SRIF1 and SRIF2 receptors.

Radioligand binding studies were performed in membranes of human cerebral cortex using [125I]Tyr3-octreotide in the presence of 5 mM MgCl2, [125I]SRIF-14 ([125I]Tyr11-SRIF-14) and [125I]CGP 23996 ([125I]c[Asu- Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) both in the presence of 120 mM NaCl, to characterise the nature of the somatostatin (SRIF) receptors. The pharmacological profile of human brain SRIF recognition sites was compared with that of recombinant human SRIF1 (sst2-sst3-sst5) or SRIF2 receptors (sst1-sst4) and with that of native rat sst1, sst2, and sst4 receptors. [125I]Tyr3-octreotide labelled binding sites in human cerebral cortex: Bmax = 238 +/- 36 fmol/mg protein and pKd = 9.73 +/- 0.08. The pharmacological profile of [125I]Tyr3-octreotide labelled sites correlated very significantly with that of recombinant human sst2 receptors (r = 0.98) and much less with those of recombinant human sst3 (r = 0.65) or sst5 receptors (r = 0.72). The correlation between [125I]Tyr3-octreotide binding to native sst2 receptors in human and rat cerebral cortex was also highly significant (r = 0.97). [125I]SRIF-14 and [125I]CGP 23996 binding (performed in the presence of 120 mM NaCl) in the human cerebral cortex identified very similar populations of sites Bmax = 44 +/- 7 and 36 +/- 5 fmol/mg protein and pKd = 9.44 +/- 0.08 and 9.48 +/- 0.10, respectively. The pharmacological profiles of the sites labelled with [125I]SRIF-14 and [125I]CGP 23996 correlated highly significantly with those of recombinant human sst1 (r = 0.97-0.99) or sst4 receptors (r = 0.91-0.94). Similarly, the correlations between [125I]SRIF-14 or [125I]CGP 23996 binding in human cortex and [125I]SRIF-14 binding to native sst1 sites in rat cerebral cortex were also highly significant (r = 0.97 and 0.94, respectively). Finally, the pharmacological profile of native rat lung sst4 sites determined with [125I]LTT-SRIF-28 ([Leu8,D-Trp22, 125I-Tyr25]SRIF-28) correlated with [125I]SRIF-14 and [125I]CGP 23996 binding in human cortex; r = 0.91 and 0.87, respectively. The present data show that in human cerebral cortex, [125I]Tyr3-octreotide labels SRIF1 receptor sites which are best characterised as of the sst2 type, whereas [125I]SRIF-14 and [125I]CGP 23996 (both in the presence of 120 mM NaCl), label sites which fit almost equally well with sst1 or sst4 receptors and therefore are best described as of the SRIF2 type. Under the conditions used, there was no evidence that either of these ligands would label sst3 or sst5 receptors in human cerebral cortex.

Animals↗
PubMed1997

Autoradiographic analysis of somatostatin SRIF1 and SRIF2 receptors in the human brain and pituitary.

The distribution of somatostatin (SRIF) receptor sites was studied by in vitro receptor autoradiography in the human brain and pituitary using the SRIF1 (sst2) receptor selective [125I]Tyr3-octreotide, the non-subtype selective [125I]LTT-SRIF-28 ([Leu8,D-Trp22, 125I-Tyr25]SRIF-28) and the SRIF2-receptor selective [125I]CGP 23996 (c[Asu- Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) in buffer containing 120 mM Na+. SRIF receptor autoradiography was compared with mRNA expression of somatostatin receptors sst1-5 as studied by in situ hybridisation in human brain. High levels of [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide recognition sites were found in the deep layers of cerebral cortex and molecular layer of cerebellum of the human brain. The hypothalamus, choroid plexus, most areas of the brainstem and dentate nucleus were associated with low levels of binding. In contrast to [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide, no difference was observed for [125I]CGP 23996 labelling in the various layers of cerebral cortex. The choroid plexus, substantia nigra and molecular layer of the cerebellum presented high densities of [125I]CGP 23996 binding sites whereas no binding was observed in the hypothalamus and locus coeruleus using this radioligand. Both lobes of the human pituitary displayed low levels of [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide binding. By contrast, the anterior lobe of the pituitary displayed very high levels of [125I]CGP 23996 labelled sites whereas intermediate levels were found in the posterior lobe. There was a partial overlap between sst2 receptor mRNA and [125I]Tyr3-octreotide binding, although the distribution of the binding sites was much wider than that of receptor mRNA. The same observation was made for sst1 and/or sst4 receptor mRNA and [125I]CGP 23996 labelled sites. The present data show that SRIF1 and SRIF2 receptors are present in the human brain with different distributions, especially in the cerebral cortex and the pituitary. The very similar distribution of sites labelled with [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide suggests (i) that sst2 receptors are predominant within the SRIF1 family in the human brain and (ii) that [125I]LTT-SRIF-28 under the conditions used in the present study, does not significnatly label SRIF2 sites.

Autoradiography↗
PubMed1997

Argyrophilic grain disease: widespread hyperphosphorylation of tau protein in limbic neurons.

Argyrophilic grains (ArG) and coiled bodies of argyrophilic grain disease (AgD) and the neurofibrillary lesions of Alzheimer's disease (AD) share similar antigenic determinants, among them hyperphosphorylated microtubule-associated protein tau. Nothing is known about the mechanisms underlying tau hyperphosphorylation in AgD, the hyperphosphorylated sites or the intracellular distribution of abnormally phosphorylated tau. We have analysed brain tissue sections from 41 subjects with AgD with a panel of phosphorylation-dependent (AT270, AT8, Tau-1, AT180, 12E8, PHF-1 and AT100) and phosphorylation-independent anti-tau antibodies (N-tau 5, 304, 189 and 134). All antibodies labelled ArG, coiled bodies and neurofibrillary lesions, with the exception of antibody 12E8, which stained a subset of neurofibrillary tangles, but no ArG or coiled bodies. Most pyramidal neurons in areas rich in ArG showed diffuse granular tau labelling in cell bodies and dendrites. Only very few tau-positive cells also contained neurofibrillary tangles. Phosphorylation-dependent anti-tau antibodies also stained a felt-like network of Gallyas-negative filiform neurites in layer CA1 of the hippocampus and in layer pre-B of the transentorhinal cortex. These results demonstrate a widespread hyperphosphorylation of tau protein in the somatodendritic domain of neurons in AgD, in addition to silver grains in the neuropil. Unlike in AD, tau hyperphosphorylation in the somatodendritic domain in AgD does not appear to be followed by neurofibrillary tangle formation, even in the presence of widespread ArG in the neuropil. Furthermore, our data suggest that no strict correlation exists between the presence or density of ArG in the limbic area and the occurrence of dementia.

Aged↗
PubMed1997

Argyrophilic grain disease: distribution of grains in patients with and without dementia.

In a previous study we reported on a late onset dementia which occurred in only half of the patients with argyrophilic grain disease (AgD) investigated. To find a correlation between the distribution of argyrophilic grains (ArG) and the occurrence of a late onset dementia, we examined the limbic area in 35 subjects who had ArG as the main neuropathological finding. A retrospective clinical analysis was performed by collecting information from hospital charts supplemented by standardized interviews based on DSM IV criteria for dementia. Sections from the rostral and caudal hippocampal regions, including the entorhinal/transentorhinal and parahippocampal cortex on both sides, were strained by the Gallays method. Nineteen subjects were diagnosed as demented according to these criteria; 16 were considered to have been cognitively normal. High numbers of ArG were observed in the anterior part of the CA1 subfield in all cases. However, the posterior half of CA1 was involved significantly more often and more severely in demented than in non-demented individuals (P < 0.01). Moreover, the distribution of ArG in the entorhinal/transentorhinal and parahippocampal cortex was more widespread in the group of demented patients (P < 0.05). These results show that the intellectual status of patients with AgD was related to the extension of ArG in the limbic area. We suggest that AgD is a progressive neurodegenerative disorder with early subclincial lesions in the anterior part of the hippocampal formation. To provide a more accurate clinicopathological correlation, the rostrocaudal extension of ArG in the limbic area should be evaluated in AgD cases.

Aged↗
PubMed1997

Development and characterization of antibodies against the N terminus of the human dopamine D4 receptor.

The human dopamine D4 receptor (hD4R), which has been implicated in human diseases such as schizophrenia and in a personality trait called "novelty seeking," has not yet been characterized at the protein level. Following epitope scanning of the hD4R, we have produced a highly specific monoclonal antibody named DFR1 raised against an amino-terminal peptide in a predicted extracellular region of the receptor. DFR1 decorated recombinant hD4Rs on the surface of intact Chinese hamster ovary (CHO) cells by flow cytometry and fluorescence microscopy and also recognized recombinant hD4.2, hD4.4, and hD4.7 receptor isoforms by western blot analysis. When expressed stably in CHO cells, all three hD4R isoforms contained N-linked glycosylation and showed apparent molecular masses of 48, 55, and 67 kDa for hD4.2, hD4.4, and hD4.7, respectively. DFR1 immunoreactivity representing hD4R protein or dopamine D4 receptor-like antigens was observed in crude membrane extracts of postmortem human brain tissue by immunoblotting. The DFR1 antibody provides a new immunological tool with the potential to further our understanding of the human dopamine D4 receptor protein.

Amino Acid Sequence↗
PubMed1997

[Ambulatory surgery in the hospital: decision between national health insurance responsibility and personal job security].

The aim of outpatient surgery is to reduce costs in the health service. However, the number of surgeons working in a surgical department is dependent upon the numbers of occupied beds. This creates an existential conflict in which, by reducing the occupancy of beds in order to take on more outpatient cases, surgeons are putting their own jobs on the line. Possible solutions are here discussed.

Ambulatory Surgical Procedures↗
PubMed1996

[Frontal lobe dementia: a case report].

Frontal lobe dementia (FDL) is a disorder that has only been described in recent years. It is mainly characterized by language disturbances and personality changes. We describe the problems and the possible therapeutic approaches to FLD, using a single case which has been well documented for several years.

Aged↗
PubMed1996

Expression of five somatostatin receptor mRNAs in the human brain and pituitary.

The messenger RNA (mRNA) expression of somatostatin receptors sst1-5 was studied in human brain by in situ hybridization histochemistry using specific oligonucleotide probes. sst1 receptor mRNA was mainly found in the outer and intermediate layers of cerebral cortex, hippocampal formation (CA1, dentate gyrus, entorhinal cortex), hypothalamus, substantia nigra, medullary nuclei and dentate nucleus. sst2 transcripts were present in the deep layers of the cerebral cortex, amygdala, hippocampal formation (CA1, dentate gyrus, subiculum, entorhinal cortex), the granular layer of the cerebellum and pituitary. sst3 receptor mRNA was localized in the cerebral cortex, hippocampal formation (CA1, dentate gyrus), several medullary nuclei and the granule and possibly Purkinje cell layer of the cerebellum and at very low levels in the pituitary. sst4 receptor mRNA was absent in the cerebral cortex. Intermediate signals were observed in the dentate gyrus of the hippocampus and several medullary nuclei while an intense expression was found in the granule and Purkinje cell layer of cerebellum. sst5 transcripts were present in the pituitary and the granule layer of the cerebellum. The present results show that mRNAs of sst1-4 somatostatin receptors have distinct distribution patterns within the human brain, although there is overlap in several regions. sst5 receptor mRNA expression appears to be very low and restricted to the cerebellum and pituitary. The distribution pattern observed in the human brain was broadly similar to that reported previously in the rat brain. The high expression levels of at least two somatostatin receptor subtype mRNAs (sst2 and sst5) in the pituitary gland suggest that somatostatin may affect neuroendocrine functions via more than one receptor.

Adolescent↗
PubMed1996

Pick's disease: hyperphosphorylated tau protein segregates to the somatoaxonal compartment.

Pick bodies and ballooned cells of Pick's disease and the neurofibrillary lesions of Alzheimer's disease are characterized by the presence of hyperphosphorylated microtubule-associated protein tau. Little is known about the mechanisms underlying tau hyperphosphorylation in Pick's disease and the distribution of abnormal tau in affected neurons. We have used a panel of phosphorylation-dependent (AT270, AT8, AT180, 12E8, PHF-1, AT10 and Tau-1) and phosphorylation-independent anti-tau antibodies (N-tau 5 and 134) to stain brain tissue sections from subjects with Pick's disease and Alzheimer's disease. These antibodies labeled Pick bodies and neurofibrillary lesions in a similar way, with the exception of antibody 12E8, which stained a subset of neurofibrillary tangles, but no Pick bodies. Moreover, abundant AT8- and PHF-1-positive neuritic profiles were observed in cortical areas rich in Pick bodies, even in the complete absence of neurofibrillary lesions. Unlike the Gallyas-positive neuropil threads of Alzheimer's disease, which were of variable diameter and covered by spiny appendages, neuritic profiles of Pick's disease showed a regular diameter, appeared smooth and were Gallyas-negative. In contrast to Alzheimer's disease, dendritic branches of neurons containing Pick bodies were not labeled by anti-tau antibodies. In the hippocampus, numerous tau-positive axon terminals were found along dendrites of the polymorphic layer of the dentate gyrus. Our results indicate that tau proteins in Pick's disease and Alzheimer's disease share similar phosphorylated residues, with the exception of serine 262, which is phosphorylated in Alzheimer tangles but not in Pick bodies or neuritic profiles. Furthermore, we show that hyperphosphorylated tau segregates to different neuronal compartments in the two diseases, with a somatoaxonal distribution in Pick's disease and a somatodendritic distribution in Alzheimer's disease.

Aged↗
PubMed1996

Localization and pharmacological characterization of somatostatin recognition sites in the human cerebellum.

Radioligand binding studies were performed in membranes of human cerebellum using [125I][Tyr3]octreotide also known as [125I]204-090, [125I]LTT-SRIF-28 ([Leu8, D-Trp22, 125I-Tyr25]SRIF-28) and [125I]CGP 23996 ([125I]c[Asu-Lys-Asn-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) to characterize the nature of cerebellar somatostatin receptors. Saturation experiments performed with [125I]204-090 suggest the presence of a single class of binding sites with high affinity: Bmax = 55.7 +/- 9.7 fmol/mg protein, pKd = 9.57 +/- 0.04. The pharmacological profile of [125I]204-090 and [125I]LTT-SRIF-28 labelled sites in human cerebellar membranes was overlapping (correlation coefficient r = 0.998) and correlated very significantly with that of recombinant human sst2 receptors (r = 0.987). By contrast, there was very little correlation with those of recombinant human sst3 (r = 0.208) or human sst5 receptors (r = 0.547). In contrast to [125I]204-090 or [125I]LTT-SRIF-28 binding, [125I]CGP 23996 binding (in 5 mM MgCl2 buffer) in cerebellar membranes was heterogeneous as indicated by biphasic competition curves produced by sst2 receptor selective ligands such as seglitide or octreotide. The pharmacological profile of the major component was closely correlated with that of human sst2 receptors (r = 0.989), whereas the minor component correlated equally well with human sst1 or sst4 receptors (r = 0.902 and 0.941, respectively). In vitro autoradiographic studies performed in cerebellar slices using [125I]204-090 and [125I]LTT-SRIF-28 demonstrated the presence of binding sites predominantly in the molecular layer, whereas weaker labelling was detected in the granular layer. The distribution of sites labelled by both radioligands was very similar. Using [125I]CGP 23996 (in 120 mM NaCl buffer), no clear difference between labeling of the molecular and granular layers was detectable; the dentate nucleus demonstrated binding sites for [125I]CGP 23996, in contrast to the very low level of binding observed with both, [125I]204-090 and [125I]LTT-SRIF-28. Together, the present data demonstrate the presence of SRIF receptors in the adult human cerebellar cortex which are, for the major population, best characterized as sst2. The SRIF receptors in the minor populations of the cerebellar cortex and the dentate nucleus most probably represent sst1 and/or sst4 sites.

Aged↗
PubMed1996

Activation of meningeal 5-HT2B receptors: an early step in the generation of migraine headache?

Several pharmaceuticals are frequently dispensed to prevent or reduce the occurrence of migraine attacks. The prophylactic effect of these drugs has been suggested to be caused through blockade of serotonin (5-HT) receptors of type 5-HT2B or 5-HT2C. To elucidate which of these receptors is involved, we first used radioligand binding assays to determine the pharmacological profile of the human and rat-5-HT2B receptor. Furthermore, the potency of drugs used in migraine prophylaxis to stimulate or inhibit 5-HT2B or 5-HT2C receptor-mediated potency of drugs used in migraine prophylaxis to stimulate or inhibit 5-HT2B or 5-HT2C receptor-mediated phosphatidyl inositol hydrolysis was measured. All these drugs were found to block both human receptors. Correlation of the receptor affinities with the potencies used in migraine prophylaxis showed significant correlations, which were better for the 5-HT2B (P = 0.001) than for the 5-HT2C receptor (P = 0.005). Migraine headache is thought to be transmitted by the trigeminal nerve from the meninges and their blood vessels. Using the reverse transcription-polymerase chain reaction, the expression patterns of all cloned G-protein-coupled serotonin receptors were analysed in various human meningeal tissues. All tissues expressed 5-HT1Dbeta, 5-HT2A, 5-HT2B, 5-HT4 and 5-HT7 mRNAs. Only trace amounts of 5-HT2C receptor mRNA were found. With organ bath experiments we showed that the 5-HT2B receptor stimulated the relaxation of the pig cerebral artery via the release of nitric oxide. Our data support the hypothesis that 5-HT2B receptors located on endothelial cells of meningeal blood vessels trigger migraine headache through the formation of nitric oxide.

Animals↗
PubMed1996

Fatal vascular leak syndrome with extensive hemorrhage, peripheral neuropathy and reactive erythrophagocytosis: an unusual complication of recombinant IL-3 therapy.

A 39-year-old patient with severe aplastic anemia (AA), resistant to therapy, received recombinant human IL-3 (rhIL-3) on a phase I/II trial. During treatment she developed disseminated skin lesions, suggestive of vasculitis, and severe progressive peripheral neuropathy culminating in complete paralysis. She died 25 days after beginning treatment from profuse bleeding. On autopsy, evidence of vascular leaks with widespread bleeding and extensive hemorrhagic involvement of peripheral nerves was found. An additional feature was massive reactive erythrophagocytosis in lymph nodes, spleen and bone marrow. The coincidence between rhIL-3 administration and the dramatic events suggest a causal relation. As a possible pathogenic mechanism, an rhIL-3 induced excessive stimulation of macrophages and production of secondary cytokines such as tumor necrosis factor (TNF) is suggested. TNF is considered as a major factor in the development of both a vascular leak and reactive erythrophagocytosis. This case report can be regarded as an example of the possible unusual pathologic phenomena we may expect to see in the near future with increasing use of growth factors.

Adult↗