Kikuchi disease presenting as a flu-like illness with rash and lymphadenopathy.

Kikuchi-Fujimoto disease (Kikuchi Disease) is a self-limited and benign systemic lymphadenitis of unknown cause, originally described by Kikuchi and Fujimoto and coworkers in 1972. Although relatively uncommon, it is increasingly discussed in the medical literature. Clinical presentation typically includes adenopathy, particularly cervical, with fever and flu-like symptoms. This constellation of symptoms, in the presence of a characteristic histiocytic necrotizing lymphadenitis, provides the clinicopathologic diagnosis. The immunopathogenesis of Kikuchi disease may lie in a hyperactive response to viral infection. We describe an African American man with Kikuchi disease, unusual in the extent of his rash and debilitation, and in the relapse of his clinical symptoms.

Unusual neurofilament composition in cerebellar unipolar brush neurons.

During antibody screening on sections of rat cerebellum, we noticed a group of small neurons which exhibited unusual staining properties. They were robustly immunopositive for the high molecular weight neurofilament protein, moderately immunostained with antibodies to the low molecular weight neurofilament protein and alpha-internexin, but only faintly immunoreactive (in PAP sections) or essentially immunonegative (in immunofluorescent sections) with all members of a panel of antibodies directed against the middle molecular weight neurofilament protein. Since neurons generally react equally well with phosphate-independent, (antibodies to) low, middle and high molecular weight neurofilament protein, we conclude that middle molecular weight neurofilament protein is present in these cells in an unusually low relative amount. These cells are found in the granular layer and appear concentrated in the flocculus, ventral paraflocculus, and vermis, particularly in the ventral uvula and nodulus (lobules IXd and X). Previous studies performed by Hockfield defined a population of neurons of similar appearance and distribution using the monoclonal antibody Rat-302, which recognized an uncharacterized 160 kDa protein. We show here that the cells described by Hockfield are identical to those we have found and furthermore that the Rat-302 antibody specifically recognizes the dephosphorylated form of the lysine-serine-proline repeated sequences of high molecular weight neurofilament protein. These cells were studied by pre-embedding immunoelectron microscopy. The nucleus is deeply indented and shows little condensed chromatin. The cytoplasm contains scattered microtubules and a larger number of neurofilaments than expected in a small cell. There are numerous large dense core vesicles, an unusual organelle consisting of ringlet subunits, and relatively little granular endoplasmic reticulum. A thin axon and a single stout dendritic trunk emanate from the perikaryon. Although the cell body and the dendritic shaft may form either complex contacts with mossy fibres (resembling those previously termed en marron synapses) or simple symmetric synapses with small boutons containing pleomorphic vesicles, most of the synaptic relations are established on the shafts of brush-like branchlets that form at the tip of the dendrite and enter one or two glomeruli. Each branchlet forms an extraordinarily extensive asymmetric synapse with the mossy fibre rosette and the subsynaptic region shows a microfibrillar web connected to the postsynaptic density. In addition to other organelles, the branchlets contain numerous mitochondria and large dense core vesicles. Short, non-synaptic appendages with few cytoplasmic organelles emanated from the cell body, dendritic shaft and branchlets.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence for GABAergic interneurons in the red nucleus of the painted turtle.

Immunocytochemical and electrophysiological evidence supporting the presence of GABAergic interneurons in the turtle red nucleus is presented. Injections of HRP into the spinal cord produced labeling of large neurons in the contralateral red nucleus. The peroxidase-antiperoxidase (PAP) method revealed smaller cells immunoreactive to an antibody against glutamate decarboxylase (GAD), the synthetic enzyme for the inhibitory neurotransmitter GABA, that were interspersed among larger immunonegative neurons. Similar small neurons were densely immunostained by antibodies to GABA-glutaraldehyde conjugates obtained from different sources and applied according to pre-embedding and postembedding protocols. Rubrospinal neurons retrogradely labeled with HRP measured 16 and 27 microns in mean minor and major cell body diameters, while GABA-like immunopositive neurons situated within the red nucleus measured 7 and 13 microns. There was very little overlap in soma size between the two cell populations. Therefore, we suggest that the GAD- and GABA-positive neurons may be local inhibitory interneurons. This notion is further supported by observations of pre-embedding immunostaining for GAD and postembedding immunostaining for GABA showing that the turtle red nucleus is amply innervated by immunoreactive axon terminals. These puncta are closely apposed to cell bodies and dendrites of both immunonegative large neurons and immunopositive small neurons. Moreover, immunogold staining at the electron microscopic level demonstrated that GABA-like immunoreactive axon terminals with pleomorphic synaptic vesicles formed symmetric synapses with cell bodies and dendrites of the two types of red nucleus cells. These ultrastructural features are commonly assumed to indicate inhibitory synapses. A moderately labeled bouton with round vesicles and asymmetric synapses was also observed. In addition, the two types of red nucleus neurons received asymmetric axosomatic and axodendritic synapses with GABA-negative boutons provided with round vesicles, features usually associated with excitatory functions. To obtain electrophysiological evidence for inhibition, intracellular recordings from red nucleus neurons were conducted using an in vitro brainstem-cerebellum preparation from the turtle. Small, spontaneous IPSPs were recorded from 7 out of 14 red nucleus cells studied. These morphological and physiological results provide strong support for concluding that the turtle red nucleus, like its mammalian counterpart, contains GABAergic inhibitory interneurons. While we have not identified the main source of input to these interneurons, in view of the scarce development of the reptilian cerebral cortex, this input is unlikely to come from the motor cortex as it does in mammals.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebellin and related postsynaptic peptides in the brain of normal and neurodevelopmentally mutant vertebrates.

The rat cerebellum was previously shown to contain two polypeptides, a hexadecapeptide termed cerebellin and an apparent metabolite des-Ser1-cerebellin. The cerebellins have a high degree of sequence homology with residues 625-641 of the polyimmunoglobulin (polyIg)-receptor adjacent to its membrane-spanning domain. Since the cerebellins are localized in Purkinje cells and enriched in synaptosomes, this might indicate that cerebellin is a specific proteolytic cleavage fragment of a synaptic protein involved in the transcytosis of an unknown ligand. Using a specific cerebellin radioimmunoassay described here combined with high-performance liquid chromatography, cerebellin immunoreactivity could be demonstrated in the cerebella of all vertebrates examined from man to chicken. Cerebellin immunoreactivity is localized to Purkinje cells in the rat, mouse, and chicken. Furthermore, cerebellin expression is under developmental regulation in both the chicken and mouse. In addition, neurodevelopmental mutations of mice that eliminate granule cells cause a large deficit in cerebellin levels, suggesting some form of transneuronal regulation.

The polypeptide PEP-19 is a marker for Purkinje neurons in cerebellar cortex and cartwheel neurons in the dorsal cochlear nucleus.

This light and electron microscopic immunocytochemical study shows that the polypeptide PEP-19, a presumptive calcium binding protein specific to the nervous system, represents an excellent marker for cerebellar Purkinje cells and dorsal cochlear nucleus (DCoN) cartwheel cells. The polypeptide clearly reveals the entire populations of both types of neurons, including their complete dendritic and axonal arborizations. Other PEP-19 containing neurons in the two regions display weak immunoreactivity restricted to the cell body or to cell body and principal dendrites. Electron microscopic localization of PEP-19-like immunoreactivity reveals similarities between this polypeptide, parvalbumin, and a 28K vitamin D-dependent calcium binding protein. However, calmodulin, which is expressed in both Purkinje and granule cells, may differ from PEP-19. Similarities between the organization of the cerebellar cortex and the DCoN superficial layers have been known for some time, with several types of neurons in one system having their presumed homologue in the other. These data provide further support for the proposed structural and functional homology between Purkinje and cartwheel neurons, and establishes PEP-19 as a useful marker for examining degeneration of these two neuronal populations in murine cerebellar mutants.

Two-color immunohistochemistry for dopamine and GABA neurons in rat substantia nigra and zona incerta.

Dopaminergic and GABAergic neurons were visualized in the same section of rat substantia nigra (SN) and zona incerta (ZI) by a two-color double immunoperoxidase procedure or by double immunofluorescence. Rabbit antiserum to tyrosine hydroxylase (TH) and sheep antiserum to glutamic acid decarboxylase (GAD), markers for catecholaminergic and GABAergic neurons, respectively, were used as primary antisera. These techniques rely on species difference of primary antisera and non-crossreactivity of linking antisera. In normal and colchicine pretreated rats, SN pars compacta (SNC), SN pars lateralis (SNL), and ZI pars medialis (area A13) contained high densities of TH-positive neurons. Relatively few TH-positive cells were scattered in SN pars reticulata (SNR) and ZI pars lateralis (ZIL). In normal rats, GAD-positive boutons were more numerous throughout SNR and ZIL than in SNC, SNL, and area A13. In colchicine pretreated rats, the majority of neurons in SNR and ZIL and few neurons in SNC, SNL, and area A13 were GAD-positive and TH-negative. This study suggests a dichotomy of both SN and ZI into a predominantly dopaminergic and a predominantly GABAergic part.

Central GABAergic innervation of neurointermediate pituitary lobe: biochemical and immunocytochemical study in the rat.

Activity of glutamic acid decarboxylase GluDCase, the biosynthetic enzyme of gamma-aminobutyric acid (GABA) was measured in low-speed homogenate supernatant of the neural and intermediate (neurointermediate) lobe (28--30 pmol of CO2 per microgram of protein per hr) and of the anterior lobe (2--4 pmol of CO2 per microgram of protein per hr). In the neurointermediate lobe, stalk transection reduced the GluDCase activity by more than 95%. By using an antiserum to rat brain GluDCase and the unlabeled antibody--peroxidase method of Sternberger, GluDCase immunoreactivity was localized in many terminals within the neurointermediate lobe of the hypophysis. In pars intermedia, immunoreactive terminals occurred in apposition to secretory cells and to glial cells and were near nonimmunoreactive axonal profiles; in pars neuralis they were apposed to pituicytes and to unlabeled axons including the neurosecretory terminals and were along fenestrated portal capillaries. GluDCase immunoreactive axons terminals exhibited diverse morphological features and would not have been identified as a distinct population without the GluDCase antiserum. No GluDCase-immunoreactivity was found in the anterior pituitary lobe. Stalk transection abolished GluDCase immunoreactivity in the neurointermediate lobe. These data provide biochemical and morphological evidence for a central GABAergic innervation of neural and intermediate lobes of the hypophysis.