Peripheral neuropathy associated with hypereosinophilia.

Three patients with hypereosinophilia showed different forms of peripheral neuropathy: severe polyneuropathy of prevalently sensory type (case 1), mild sensory neuropathy (case 2), acute mononeuropathy of the median nerve with subclinical polyneuropathy (case 3). Hypereosinophilia was probably idiopathic, however the presence of atypical findings suggested transition to vasculitides or collagen disease. Sural nerve biopsy in cases 1 and 2 showed features of axonopathy in both, although of different severity, reflecting the variability of clinical involvement and, probably, heterogeneous pathogenic mechanisms. Peripheral nerve involvement associated with hypereosinophilia may be related to neurotoxicity of eosinophils, or to vascular damage.     

Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders

Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt-Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti-AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C-reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt-Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age-matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits.     

Evidence that 3α-hydroxy-5α-pregnan-20-one is a physiologically relevant modulator of gaba-ergic neurotransmission

3α-Hydroxy-5α-pregnan-20-one (HPO) is a progesterone metabolite which exhibits narcotic properties at high concentrations by interactions with the receptor for gamma-aminobutyric acid (GABA). The present investigation characterized low-dose effects of HPO on GABA_A receptor binding, by determining the allosteric properties of HPO on the in vitro binding of ³H-muscimol to membrane fractions from the cerebella of ovariectomized rats. A newly developed method for tissue preparation was used to wash out endogenous ligands interfering with the assay. HPO reduced the affinity of ³H-muscimol to GABA_A receptor sites by 52% and enhanced the number of accessible binding sites from 5.5±0.5 to 7.5±1.3 pmol/mg protein at subnanomolar (0.1 nM) HPO concentrations. The modulatory effects of HPO on GABA_A receptor binding provide evidence that this pregnane steroid might be a physiologically relevant modulator of GABAergic neurotransmission.     

Platelet 5-hydroxytryptamine increases with platelet age in dogs.

Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.     

Differences in the abilities of human tau isoforms to promote microtubule assembly.

Three isoforms of human tau protein were compared for their abilities to induce microtubule assembly. The three isoforms, tau 3 (tau containing three microtubule-binding domains), tau 4 (tau containing four microtubule-binding domains) and tau 4L (tau containing four microtubule binding domains plus a 58-amino-acid insert near the N-terminus) were expressed in E. coli and purified using ammonium sulfate precipitation, ion exchange, and size exclusion chromatography. All three isoforms induced microtubule assembly at micromolar concentrations and showed similar critical concentrations for assembly of 0.4-0.45 microM. However, tau 4 induced microtubule formation at a rate five- to tenfold faster than either tau 3 or tau 4L. The rate of microtubule elongation seen with tau 4 was twofold greater than with tau 3 or tau 4L, suggesting that the faster rate of microtubule assembly seen with tau 4 was due, at least in part, to faster elongation. Tau 4 induced a greater number of microtubules to form at steady state than did tau 3 or tau 4L. The microtubules generated with each tau isoform had similar steady-state length distributions and were equally susceptible to cold-induced disassembly. These results indicate that the additional microtubule-binding domain in tau 4 enhances microtubule assembly, while the 58-amino-acid insert negates the stimulatory effect of the fourth microtubule-binding domain.     

Development of rostrocaudal dendritic bundles in rat thoracic spinal cord: analysis of cholinergic sympathetic preganglionic neurons.

Using monoclonal antibodies to choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP), we have analyzed the development of the dendritic bundles formed by cholinergic sympathetic preganglionic neurons (SPNs) in relationship to changes in the organization of glial fibers. In adult rat thoracic spinal cord, SPNs in the intermediolateral (IML) and central autonomic (CA) regions extend dendrites in both the mediolateral and rostrocaudal directions, forming a ladder-like pattern in horizontal sections of thoracic spinal cord. We report that, while the mediolateral dendrites form prenatally, the rostrocaudal dendritic bundles are not detected until at least a week later, during early postnatal life. The rostrocaudal dendrites develop rapidly during the first postnatal week, and achieve an adult-like pattern by postnatal day 14. The observed ontogenetic arrangements of dendritic bundles were correlated with the developing organization of astroglial processes with which they are intimately associated. While the appearance of mediolateral dendrites is consistent with the radial organization of glial in the embryonic spinal cord, the developmental time course of the rostrocaudal dendritic bundles coincides with the transformation of glial cells from this predominantly radial or transverse orientation to the randomly-oriented, stellate pattern of mature astrocytes. This temporal association suggests that ontogenetic changes in the organization of glial cells may contribute to the differential development of mediolateral and rostrocaudal dendritic patterns in the spinal cord.     

Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum

The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.     

Submandibular sialolithiasis: transoral excision

In 17 cases the author has removed intraglandular submandibular calculi by an oral route utilizing blunt soft tissue dissection after an incision of the mucosa only. General anesthesia is used and the patient discharged after an overnight stay. No complications were encountered. All patients were back on full diet in 48 hours.     

Microscopic endonasal surgery of the paranasal sinuses and the parasellar region

The anatomic principles and operative techniques currently applied to functional endoscopic endonasal surgery have allowed for significant refinements in another approach to regional pathology that uses the operating microscope, newly designed sinus instruments, and a self-retaining nasal speculum system. The main benefits of this method are the superb widefield stereoscopic vision and the distinct freedom to work bimanually. Additionally, direct bipolar cautery of bleeders is afforded while use of the observer tube or video allows for excellent teaching. The precise nature of this surgery affords less fear of serious complications in the treatment of periorbital, paranasal sinus, and parasellar diseases. We describe technical aspects of the surgery and associated complications in 219 patients treated from 1984 to 1987.