Clinical usefulness of urinary diacetylpolyamines as novel tumor markers

N1,N12-Diacetylspermine(DiAcSpm) and N1,N8-diacetylspermidine(DiAcSpd) are excreted in the urine of healthy persons as minor components of urinary polyamine, with small individual variations in amount. They are promising tumor markers, since their excretion is frequently elevated in patients with various types of cancers. DiAcSpm is sensitive in cancer detection, while DiAcSpd is highly specific for cancer. Diacetylpolyamines were initially characterized and determined by HPLC fractionation, followed by enzymatic detection. More recently, antibodies highly specific for DiAcSpm and DiAcSpd were developed, and an ELISA system applicable to the determination of urinary DiAcSpm was established. Measurement of urinary DiAcSpm using this ELISA system revealed that DiAcSpm is a more sensitive tumor marker than CEA, CA19-9 and CA15-3 for colon and breast cancers. More importantly, DiAcSpm efficiently detects patients at early stages. On the other hand, CEA, CA19-9 and CA15-3 are quite insensitive for early stage cancers. The urinary DiAcSpm level tends to remain low even in tumor-bearing individuals when their cancerous lesions remain static, while it rises rapidly concomitant with recurrence. DiAcSpm may serve as a prognostic indicator and marker for recurrence of prostate and colon cancers. Diacetylpolyamines may turn out to be general tumor markers, since active proliferation of any cancer tissues would likely be accompanied by activation of polyamine metabolism.     

Alterations in Nonspecific Cross-reacting Antigen Localization during Cell Culture

Nonspecific cross reacting antigen (NCA), a constituent of the carcinoembryonic antigen family, was localized ultra-structurally in a human lung adenocarcinoma cell line, PC 9. NCA was distributed predominantly on the plasma membrane in the early phases of cell culture. Deletion of fetal bovine serum (FBS) from the culture medium suppressed cell division without significantly altering cell viability, and induced a dramatic but reversible change in NCA localization. Under these conditions, NCA was localized to membrane degradation products within cytoplasmic vesicles and vacuoles. Acid phosphatase activity was also present in some of these intracellular structures. Similar changes in NCA localization were seen in cells cultured with FBS at day 6 when the cells reached a plateau stage of growth. These findings strongly suggest that plasma membrane degradation is accelerated by the cessation of cell growth. Cytoplasmic reactivity for NCA in cancer cells may therefore reflect degradation of plasma membrane-associated NCA and may not necessarily be correlated with increased systhesis of this glycoprotein. Acta Pathol Jpn 39: 772 778, 1989.     

Vinyl polymerization by metal complexes, 11. Formation of polyvinylamine-copper(II) chelates

In order to clarify the mechanism of catalysis of polyvinylamine-copper(II) chelates on the initiation of vinyl polymerizations, stability constants of these chelates were measured by applying a modification of BJERRUM'S method, and each concentration of the chemical species was estimated on the basis of the chelate theory. From these results, the activity of the polyvinylamine-copper(II) chelates for the polymerization of acrylonitrile and methyl methacrylate at different pH values was discussed.     

Electron-dense deposition patterns and the outcomes of idiopathic membranous nephropathy in Japanese

A considerable diversity in prognosis is seen with membranous nephropathy (MN). In terms of pathological findings, the presence of tubulointerstitial lesions was emphasized as a poor prognostic factor. However, the glomerular factors affecting the long-term outcome of idiopathic human MN have remained unclear. We reviewed the initial clinicopathological factors affecting the primary and secondary outcomes in 105 patients with primary MN, as well as reviewing previous reports. Based on electron microscopic (EM) findings, we could divide patients into two subtypes and one subgroup; i.e., homogeneous type with a synchronous phase of electron-dense deposits, with large dense deposits (deep subgroup) and heterogeneous type with various phases of dense deposits. The homogeneous type showed no endstage renal failure, and had earlier remission as compared with the heterogeneous type. For the secondary outcome, heterogeneous type and deep subgroup were also independent risk factors. However, there was no significant difference in the final primary or secondary outcome for any treatment subgroups. These results indicated that our category of EM findings was a beneficial marker of the primary and secondary outcomes in MN; the homogeneous type of MN with synchronous phase of electron-dense deposits (except for the "deep" subgroup) had a good outcome.     

Vinyl polymerization by metal complexes, 20. Initiation by vinylamine/vinyl alcohol copolymer · copper(II) systems

The polymerization of acrylonitrile (AN) and of methyl methacrylate (MMA) initiated by various copper(II) chelates was studied in the presence of carbon tetrachloride. Several vinylamine (VAm)/vinyl alcohol (VA) copolymers with different contents of NH₂ and OH bearing monomeric units were chosen as polymer ligands as well as polyvinylamine (PVAm)/poly(vinyl alcohol) (PVA) mixtures (of equal NH₂ and OH group contents as the corresponding copolymers), PVAm, and PVA. The activity of the used polymer chelates to initiate the AN and the MMA polymerization was compared at various pH values of the reaction systems. For the polymerization of MMA, the VAm/VA copolymer systems showed a higher activity than the PVAm chelate containing the same amount of NH₂ groups, contrary to the case of the polymerization of AN, where the polymerization activity showed a reverse behavior. The initiation mechanism is discussed.     

Vinyl polymerization by metal complexes, 19. Formation of copper(II) chelates of vinylamine/vinyl alcohol copolymers

Chelate formation of vinylamine/vinyl alcohol copolymers with copper(II) was studied both by the spectrophotometric and by titrimetric methods. For comparison, polyvinylamine/poly(vinyl alcohol) mixtures were also taken up for measurements. In the case of the copolymer systems, copper(II) ions were found to be coordinated exclusively by nitrogen atoms of the copolymer ligand. The complexation constants of the chelates were determined by applying the modified Bjerrum method, in neglect of the acid dissociation of hydroxy groups in the copolymers. It was found that the copolymer/Cu(II) chelates tend to be unstable with decreasing contents of NH₂ groups in the copolymers. In the homopolymer mixture systems, copper(II) ions are not coordinated by the oxygen atoms of poly(vinyl alcohol), but only by the nitrogen atoms of polyvinylamine.     

Comparative anatomical study of the m. retractor bulbi with special reference to the nerve innervations in rabbits and dogs

Detailed dissection was performed on eight head halves of four rabbits and six head halves of three dogs in order to investigate the nerve distributions to the m. retractor bulbi. Our observations indicated that the muscle was innervated by the branches of the abducens nerve in all sides which were examined in the present study. In addition, we observed that the ventral ramus of the oculomotor nerve gave rise to branches to the m. retractor bulbi in three sides of the rabbits, and in two sides of the dogs, which suggests that the innervation pattern of the muscle is variable even in the identical species. Considering these observations, we propose that the anlage of the m. retractor bulbi is mainly composed of the anlage innervated by the abducens nerve, and occasionally the anlage innervated by the ventral ramus of the oculomotor nerve is added to it, because the anlage of the m. retractor bulbi may be formed near the border region between the anlages innervated by the oculomotor and abducens nerves.     

Three-dimensional helical coiling structures and band patterns of hydrous metaphase chromosomes observed by low vacuum scanning electron microscopy

Helical coiling structures and band patterns of hydrous metaphase chromosomes were documented three-dimensionally by low vacuum scanning electron microscopy (SEM). Fixed or unfixed isolated Chinese hamster metaphase chromosomes were stained with platinum blue (Pt blue) and observed in the backscattered electron mode for low vacuum SEM without any hypotonic treatment or drying processes. Fibrous structures were shown both in the fixed and unfixed hydrous chromosomes; helical chromatid coils and their subcoils were clarified especially in the fixed chromosomes having contrasting alternative bands of light and darkness, while the translucent perichromosomal matrix and compact fibrous structures were recognized in the unfixed chromosomes. The helical coils were more clearly represented in a loosened chromatid of metaphase chromosomes. Treatment with a tris-HCl buffer solution and Pt blue staining in a hydrous condition successfully produced banding patterns similar to G-bands on metaphase chromosomes. These banded chromosomes observed by low vacuum SEM were also analyzed stereoscopically by field emission SEM after critical point drying. These findings indicate that: 1) native or unfixed chromosomes maintain the compact arrangement of high-order helical structures covered with the peri-chromosomal matrix; 2) helical coiling appearances of chromatids frequently observed in previous papers might be caused by loosening of the final level of the high-order structure of the metaphase chromosome; and 3) banding patterns might be produced by the rearrangement or reorganization of chromatin fibers at the 30 nm fiber level after the extraction of some chromosomal components including the peri- or intra-chromosomal materials during the banding procedure.     

Immune aspects of intestinal metaplasia of the stomach: An immunohistochemical study

Summary Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.