No abstract

Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61)

The ascidian larva is an excellent model for studies of the functional organization and neuronal circuits of chordates due to its remarkably simple central nervous system (CNS), comprised of about 100 neurons. To date, however, the identities of the various neurons in the ascidian larva, particularly their neurotransmitter phenotypes, are not well established. Acetylcholine, GABA, and glycine are critical neurotransmitters for locomotion in many animals. We visualized putative cholinergic neurons and GABAergic/glycinergic neurons in the ascidian larva by immunofluorescent staining using antibodies against vesicular acetylcholine transporter (VACHT) and vesicular GABA/glycine transporter (VGAT), respectively. Neurons expressing a cholinergic phenotype were found in the brain vesicle and the visceral ganglion. Five pairs of VACHT-positive neurons were located in the visceral ganglion. These putative cholinergic neurons extended their axons posteriorly and formed nerve terminals proximal to the most anterior muscle cells in the tail. VGAT-positive neurons were located in the brain vesicle, the visceral ganglion, and the anterior nerve cord. Two distinct pairs of VGAT-positive neurons, bilaterally aligned along the anterior nerve cord, extended axons anteriorly, near to the axons of the contralateral VACHT-positive neurons. Cell bodies of the VGAT-positive neurons lay on these nerve tracts. The neuronal complex, comprising motor neurons with a cholinergic phenotype and some of the GABA/glycinergic interneurons, has structural features that are compatible with a central pattern generator (CPG) producing a rhythmic movement of the tail. The simple CPG of the ascidian larva may represent the ancestral state of the vertebrate motor system.

Preoperative smoking abstinence of longer than 3 weeks reduces the incidence of impaired wound healing among patients who have undergone reconstructive head and neck surgery.