Shukuro Araki

Identification of amyloid prealbumin variant in familial amyloidotic polyneuropathy (Japanese type)

Structural studies on an amyloid fibril protein of 14 K daltons (AFj(INO] isolated from a Japanese patient who suffered from familial amyloidotic polyneuropathy were carried out to unambiguously identify its difference from normal human serum prealbumin. Sequence analyses performed by comparing peptide maps prepared from cyanogen bromide fragments and tryptic peptides of purified RCM-amyloid protein with those from RCM-prealbumin indicate that only a valine residue at position 30 in prealbumin is replaced by a methionine residue. Furthermore, it was also proved that AFj(INO) consists of four components; the prealbumin variant and its three related proteins, which are derived by successively accumulated deletion of the N-terminal three amino acid residues (Gly1, Pro2 and Thr3) from the prealbumin variant.

Cloning and sequence analysis of cDNA for human prealbumin.

A cDNA coding for human prealbumin has been cloned from a cDNA library prepared from human liver. The DNA sequence codes for a polypeptide which consists of 147 amino acids including a whole human prealbumin sequence and a putative signal sequence. The elucidation of this prealbumin cDNA sequence is expected to facilitate a prenatal diagnosis of familial amyloidotic polyneuropathy.

Type I familial amyloidotic polyneuropathy (Japanese type).

Our recent studies on familial amyloidotic polyneuropathy (FAP) were reviewed. Since the clinical picture of our FAP is slightly different from those of the Portuguese type, the Swedish type, and the Jewish type, structural identification of the amyloid fibril proteins should be clarified on a molecular basis. Further investigation on the effectiveness of dimethyl sulfoxide (DMSO) or a search for other useful new drugs is greatly required.

Familial amyloidotic polyneuropathy type 1 in Kumamoto, Japan: A clinicopathologic, histochemical, immunohistochemical, and ultrastructural study

Seventeen autopsy and five biopsy cases of familial amyloidotic polyneuropathy were examined clinicopathologically, histochemically, immunohistochemically, and ultrastructurally. In the autopsy cases, amyloid deposits were predominant in the peripheral nerve tissues, autonomic nervous system, choroid plexus, cardiovascular system, and kidneys. Amyloid involvements in the anterior and posterior roots of the spinal cord, spinal ganglia, thyroid, and gastrointestinal tract were also frequent. In the cardiac conduction system, amyloid deposition was prominent in the sinoatrial node and in limbs of the intraventricular bundle. In the sural nerve biopsy, besides amyloid deposits, degenerative changes of nerve fibers and Schwann cells were detected ultrastructurally, and the morphometric analysis showed a marked reduction in the number of myelinated fibers which correlated with the clinical stage. Amyloid deposits were resistant to pretreatment with potassium permanganate in Congo red staining, and transthyretin was confirmed immunohistochemically as a major component of amyloid deposits, along with the presence of serum amyloid P-component. Besides the amyloid deposits, transthyretin was proven in the liver cells, epithelial cells of the choroid plexus, and pancreatic islet A cells, suggesting that the transthyretin produced by these cells is secreted, transferred into tissues, and deposited in situ as the major component of amyloid in this disorder.

Revised analysis of amino acid replacement in a prealbumin variant (SKO-III) associated with familial amyloidotic polyneuropathy of Jewish origin.

Amyloid fibril protein (SKO-III) of 14K daltons associated with familial amyloidotic polyneuropathy of Jewish type was identified by Pras et al. as a prealbumin variant with a single amino acid substitution of a glycine for a threonine at position 49, mainly based on data obtained by automated sequence analyses. Structural re-investigation of SKO-III was performed by comparing tryptic peptide maps of SKO-III and normal human prealbumin. The present analysis reveals that the reported replacement at position 49 is not present in the molecule of SKO-III. SKO-III should be revised to be a prealbumin variant with one amino acid substitution of an isoleucine for a phenylalanine at position 33.

Identification of a prealbumin variant in the serum of a Japanese patient with familial amyloidotic polyneuropathy

Serum prealbumin isolated from a Japanese patient with familial amyloidotic polyneuropathy (FAP) has been found to consist of a mixture of normal prealbumin and a prealbumin variant which contains a methionine for valine substitution at position 30. The prealbumin variant in the serum is identical to the prealbumin variant derived from amyloid fibrils of a Japanese FAP patient. FAP likely results from the deposition of abnormal serum prealbumin in various organs as amyloid fibrils.

Differential regulation of IgA production by TGF-β and IL-5: TGF-β induces surface IgA-positive cells bearing IL-5 receptor, whereas IL-5 promotes their survival and maturation into IgA-secreting cells☆

Transforming growth factor beta (TGF-beta) and IL-5 have been shown to augment IgA production by LPS-stimulated murine B cells. We investigated the effect of TGF-beta on the expression of surface Ig-isotype and IL-5 receptor on LPS-stimulated B cells. TGF-beta increased the proportion of both surface IgA-positive (sIgA+) B cells and sIgG2b+ B cells and enhanced IgA and IgG2b production by LPS-stimulated B cells. TGF-beta synergized with IL-5 only for IgA production of the seven Ig-isotypes and in combination with IL-5 caused a significant increase in the proportion of sIgA+ B cells up to 17.4%. In contrast, IL-5 decreased the proportion of sIgG2b+ B cells and sIgG3+ B cells and inhibited the production of IgG2b and IgG3 by LPS-stimulated B cells. About 50% of sIgA+ cells induced by TGF-beta expressed IL-5 receptor. They secreted peak levels of IgA and seemed to maintain long viability in the presence of IL-5; whereas TGF-beta had the opposite effects on sIgA+ B cells and down-regulated the IL-5 receptor expression. These results indicate that TGF-beta increases the number of sIgA(+)- and IL-5 receptor-positive B cells which respond to IL-5 giving rise to IgA-secreting cells and also support the notions that TGF-beta preferentially induces switching to sIgA+ B cells and IL-5 induces the maturation of postswitch sIgA+ B cells into IgA-secreting cells in a stepwise fashion.

Toxic polyneuropathy due to glue-sniffing: Report of two cases with a light and electron-microscopic study of the peripheral nerves and muscles

Abstract Two patients with polyneuropathy following glue-sniffing are reported. They were 20- and 19-year-old painters in the same workshop who each developed a subacute, predominantly motor polyneuropathy after sniffing glue vapours for 3 and 2.5 years respectively. The polyneuropathy progressed for 3 months even after exposure ceased and marked weakness of the extremities with severe neurogenic atrophy of skeletal muscle was distinctive. The glue was proved by gas liquid chromatography to contain both n-hexane and toluene as volatile substances. While n-hexane seems likely to have been the major cause, toluene may have participated in producing the polyneuropathy. Sural nerve biopsies demonstrated extensive nerve damage due to axonal degeneration especially in large diameter fibres. There was no evidence of regeneration in the nerves even 3 months after exposure ceased. It is concluded that n-hexane plus toluene, but especially n-hexane, acted on the axis cylinders of the peripheral nerves, resulting in axonal degeneration, thus producing a predominantly motor polyneuropathy with marked neurogenic muscular atrophy.

Characterization of the antigen recognized by a monoclonal antibody MN9: unique transport pathway to the equatorial segment of sperm head during spermiogenesis.

SummaryMN9, a monoclonal antibody raised against mouse spermatozoa, specifically recognizes the equatorial segment of sperm head in several mammalian species, including humans. Colloidal gold-immuno-electron microscopy of mouse spermatozoa has shown that the antigen is localized in the space between the outer and inner acrosome membranes and on the acrosome membranes at the equatorial segment. Immunoblotting after electrophoresis of spermatozoa from the cauda epididymidis has identified two immunoreactive bands: 38 kDa and 48 kDa in mouse, and 48 kDa in rat. During spermiogenesis in rat, this antigen is transported to the equatorial segment via a unique pathway, first appearing in some cisternae of the endoplasmic reticulum and in the Golgi apparatus of spermatids at around step 3. The antigen can further be found on the vesicles at thetrans-side of the Golgi apparatus, in the matrix of the head cap, and on the head cap membrane in step-4 to step-7 spermatids. The antigen appears to be concentrated at the equatorial segment during late spermiogenesis. Neither the (pro-)acrosomic granule nor the surrounding membrane are required in this pathway. This pathway can be termed the ‘Golgi-head cap tract’.

Hydrocephalus, corneal opacities, deafness, valvular heart disease, deformed toes and leptomeningeal fibrous thickening in adult siblings : a new syndrome associated with -glucocerebrosidase deficiency and a mosaic population of storage cells

We describe three adult siblings with communicating hydrocephalus, corneal opacities, deafness, valvular heart disease, and deformed toes associated with glucosylceramide (glc‐cer)‐β‐glucosidase deficiency. The common manifestations of Gaucher disease were not evident. Supranuclear gaze palsies characteristic of type 3 were noted from early childhood, although the major signs were undeveloped until early adult life. Autopsy disclosed thickened leptomeninges with perivascular fibrosis, non‐rheumatic calcified aortic and mitral stenosis with marked fibrosis, and mild infiltration of Gaucher cells in the reticuloendothelial organs. In contrast to the slight accumulation of glc‐cer in the liver and spleen, the activity of glc‐cer‐β‐glucosidase was markedly decreased in the tissues, as much as in a patient with type 2 Gaucher disease. Common mutations were not found in the glucocerebrosidase gene.