Choline acetyltransferase (ChAT), the enzyme responsible for the biosynthesis of acetylcholine, is presently the most specific indicator for monitoring the functional state of cholinergic neurones in the central and peripheral nervous systems. ChAT is a single-strand globular protein. The enzyme is synthesized in the perikaryon of cholinergic neurones and transported to the nerve terminals probably by both slow and rapid axoplasmic flows. ChAT exists in at least two forms in cholinergic nerve terminals: (i) soluble; and (ii) non-ionically membrane-bound forms. Multiple mRNA species of ChAT (R-, N-and M-types) are transcribed from different promoter regions and produced by different splicing in the mouse, rat, and human. All transcripts encode the same ChAT protein in rodents, while in human M-type mRNA has the capability to generate both large and small forms of ChAT proteins and R-and N-types ChAT mRNA generate a small form, which corresponds to the rodent ChAT. The genomic structure of ChAT is unique compared with other enzymes for neurotransmitters. The first intron of the ChAT gene encompasses the open reading frame encoding another protein, vesicular acetylcholine transporter (VAChT), which is responsible for the transportation of acetylcholine from the cytoplasm into the synaptic vesicles. The expressions of ChAT and VAChT appear to be coordinately regulated by multiple regulatory elements in cholinergic neurones. Immunohistochemical and in situ hybridization studies have revealed the localization of cholinergic neurones in the central nervous system: the medial septal nucleus, the nucleus of the diagonal band of Broca, the basal nucleus of Meynert, the caudate nucleus, the putamen, the nucleus accumbens, the pedunculopontine tegmental nucleus, the laterodorsal tegmental nucleus, the medial habenular nucleus, the parabigeminal nucleus, some cranial nerve nuclei, and the anterior horn of the spinal cord. Focally distributed cholinergic neurones project fibers to many areas in the central nervous system and construct a complicated cholinergic network, playing an important role in neuropsychic activities, such as learning, memory, arousal, sleep and movement. Central cholinergic neurones are involved in several neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis, in which disturbance of the central cholinergic system does not appear to be closely related to the etiology, but rather to the development of clinical symptoms. In addition, abnormalities of ChAT in the brain have been recently demonstrated in schizophrenia and sudden infant death syndrome.

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This study represents a systematic analysis of the distribution of collagen types in human atherosclerotic lesions. Formalin-fixed, paraffin-embedded aortic tissues of 40 lesions from 16 different individuals ranging in age from 1 month to 84 years were examined immunohistochemically using antibodies to type I, III, IV, V, and VI collagens. Preembedding immunoelectron microscopy was used to simultaneously localize type V and VI collagens within the lesions. Localization of type HI collagen was very similar to that of type L and type VI collagen appeared together with these two types of collagen in the thickened intlmas of all stages of the lesion. Type V collagen was not detected in either fatty streaks or the mild Intimal thickening of the aortas of children. With advancing age and lesion progression, the immunoreactivity with anti-type V collagen antibody became more intense. Type IV collagen was detected in the basement membrane region of intimal cells. In advanced lesions thick deposits of type IV collagen were found around the elongated smooth muscle cells. Using immunoelectron microscopy, type V collagen was found to be localized to cross-banded collagen fibers, and type VI collagen was found to be localized to beaded filaments present throughout the interstitium of the thickened intima. These findings suggest that collagens preserve the pathophysiological and functional integrity of the vascular wall by providing mechanical support as well as assuring the proper interaction of cells during the formation of atherosclerotic lesions. (Arteriosclerosis and Thrombosis 1992;12:494-502) KEYWORDS • atherosclerosis • collagen • immunohistochemistryA therosclerosis is a disease of large and medium-/ \ sized arteries and is characterized by focal X A . thickening of the inner portion of the artery wall in association with fatty deposits.1 -2 The common underlying events responsible for lesion formation are intimal smooth muscle cell proliferation, formation of new extracellular matrix by these cells, and the possible accumulation of lipid. Collagens are regarded as important in this disease not only because they represent the major extracellular component in the atherosclerotic plaque and thereby contribute to the occlusive nature of the disease but also because they may play an important role in hemostasis and thrombosis through stimulation of blood platelets. 3 In addition, recent studies have indicated that collagens can influence the proliferation and state of differentiation of smooth muscle cells in vitro.4 -6 Thus, it seems likely that collagens could play a vital role in the pathogenesis of this disease.Collagen is now recognized as a family of proteins of at least 13 genetically distinct subtypes, each of which has a unique tissue specificity. -9 Of these 13 collagen types, six (I, III, IV, V, VI, and VIII) are present in blood vessels. 10 All of these collagen types except type VIII collagen are known to be synthesized by smooth From the Department of Pathology, School of Medicine, Kanazawa University, K...

Marginal halo and relatively higher echogenicity on EUS might suggest GIST. Marginal lobulation and a short doubling time may be signs of a malignant GIST.

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