Prolonged survival of rat hepatic allografts after total-body irradiation of the donors.

The effect of total-body irradiation of the donor on hepatic allograft survival was studied in the rat, with ACI(RT1a) as the donor and LEW(RT1(1)) as the recipient. LEW recipients of ACI liver transplants experienced severe acute rejection, with a mean survival of only 10.2 +/- 0.3 days. The doses of irradiation were 450, 750, and 1000 rads administered 24 hr prior to harvesting or subsequent transplantation. TBI with a dose of 750 rads significantly prolonged the survival of the hepatic allograft to 30.3 +/- 1.7 days, without concomitant immunosuppression. However, neither 450 rads nor 1000 rads of TBI resulted in successful suppression of graft rejection. TBI appeared to have a beneficial effect on hepatic allograft survival and to have no deleterious effect on isograft survival, suggesting a possible modulation of the immunogenicity of the donor organ. Although the cause of this beneficial effect is not clear, TBI with a dose of 750 rads 24 hr prior to organ harvest seems to be optimal to eliminate-antigen presenting cells in the donor organs.     

Management of polyuria subsequent to pituitary surgery based on the diurnal pattern of urinary excretion

Polyuria subsequent to pituitary surgery was studied in 64 cases. Most cases of postoperative polyuria were due to diabetes insipidus. These cases showed a triphasic pattern in daily urinary volume. Observation of hourly urinary volume in polyuria revealed four diurnal patterns of urinary excretion: rhythmic, continuous, transient, and unspecific. Clinical observation of diurnal patterns has an advantage, in terms of simplicity of procedure, in immediately determining the nature of the polyuria, prognosticating diabetes insipidus, and eliminating inappropriate procedures in treatment. Indomethacin suppository is considered to be a favorable agent in reducing polyuria without disturbing the diurnal pattern in diabetes insipidus.     

Hemoglobin values in adult women of various occupational groups in the community

In 1966 and 1971, the authors studied hemoglobin values of about 2,000 women of 10 different occupational groups and different social classes in the same district. The mean values of hemoglobin and serum iron were highest in nursing students followed by urban housewives and nutritionists and lowest in 3 groups of farm wives and shoe factory laborers. The difference in the mean values of hemoglobin observed among occupational groups was in principle assumed to be due to the difference of frequency in levels of 11-12 g/dl. Hemoglobin levels between 1966 and 1971 tended to improve as a whole and the differences among occupational groups have been reduced. In this study, some kinds of social conditions as well as some physiological factors related to hemoglobin values were investigated. In the same occupational group, unmarried women had a higher level of hemoglobin than married women. Further, married women with infants showed a relatively lower level than those with no infants. This suggests that hemoglobin values of female workers may be significantly influenced not only by work conditions but also by social conditions including family circumstances.     

Single-membrane–bounded peroxisome division revealed by isolation of dynamin-based machinery

Peroxisomes (microbodies) are ubiquitous single-membrane–bounded organelles and fulfill essential roles in the cellular metabolism. They are found in virtually all eukaryotic cells and basically multiply by division. However, the mechanochemical machinery involved in peroxisome division remains elusive. Here, we first identified the peroxisome-dividing (POD) machinery. We isolated the POD machinery from Cyanidioschyzon merolae, a unicellular red alga containing a single peroxisome. Peroxisomal division in C. merolae can be highly synchronized by light/dark cycles and the microtubule-disrupting agent oryzalin. By proteomic analysis based on the complete genome sequence of C. merolae, we identified a dynamin-related protein 3 (DRP3) ortholog, CmDnm1 (Dnm1), that predominantly accumulated with catalase in the dividing-peroxisome fraction. Immunofluorescence microscopy demonstrated that Dnm1 formed a ring at the division site of the peroxisome. The outlines of the isolated dynamin rings were dimly observed by phase-contrast microscopy and clearly stained for Dnm1. Electron microscopy revealed that the POD machinery was formed at the cytoplasmic side of the equator. Immunoelectron microscopy showed that the POD machinery consisted of an outer dynamin-based ring and an inner filamentous ring. Down-regulation of Dnm1 impaired peroxisomal division. Surprisingly, the same Dnm1 serially controlled peroxisomal division after mitochondrial division. Because genetic deficiencies of Dnm1 orthologs in multiperoxisomal organisms inhibited both mitochondrial and peroxisomal proliferation, it is thought that peroxisomal division by contraction of a dynamin-based machinery is universal among eukaryotes. These findings are useful for understanding the fundamental systems in eukaryotic cells.Peroxisomes are single-membrane–bounded organelles found in nearly all eukaryotic cells. In plant cells, peroxisomes are involved in a variety of metabolic pathways essential for development associated with photorespiration, lipid mobilization, and hormone biosynthesis (1, 2). In animals, abnormalities in peroxisome proliferation are associated with carcinogenesis, neurodegeneration, and cerebrohepatorenal syndrome (1, 3). Peroxisomes are thought to basically proliferate by division, although they do not contain DNA (1). Because the cells of multiperoxisomal organisms, such as yeasts, plants, and animals, contain irregularly shaped peroxisomes that divide randomly, their proliferation has been examined by analyzing peroxisome abundance and distribution (4, 5). Therefore, the division machinery (ring) that is essential for proliferation and plays a central role is unclear. Cyanidioschyzon merolae offers unique advantages for studying peroxisomal division, because each cell contains a minimal set of basic eukaryotic organelles, comprising one chloroplast, one mitochondrion, one cell nucleus, and one peroxisome, the divisions of which occur in that order and can be synchronized by light/dark cycles (6–9) (Fig. 1 A and B and Fig. S1). In C. merolae, peroxisomes do not form de novo from the endoplasmic reticulum in the peroxisomal division cycle but divide by binary fission (6, 7, 10). In addition, the complete sequence of the genome has enabled proteomic analyses (7, 11).Open in a separate windowFig. 1.Identification of Dnm1 from the dividing-peroxisome fraction. (A) Immunofluorescence and schematic images of mitochondrial and peroxisomal divisions of C. merolae. Peroxisomal (red) division occurred after mitochondrial (yellow) division. Chl, chloroplast; Mt, mitochondrion; Nu, nucleus; PC, phase-contrast image; Po, peroxisome. (B) Frequencies of dividing cell nuclei (Nu), dividing chloroplasts (Chl), dividing mitochondria (Mt), and dividing peroxisomes (Po) in non–oryzalin-treated cells (control) and oryzalin-treated cells (Orz+) at the indicated times after synchronization (n > 100). (C) Proteomic analysis of peroxisomal fractions in control and oryzalin-treated cells at 20 h after synchronization. The major bands specific to oryzalin-treated cells were identified as catalase (black arrowhead), Dnm1 (red arrowhead), and others. (D) Immunoblot analyses of Dnm1, catalase, mitochondria division protein (Mda1), porin, and chloroplast division protein (PDR1). Cell, whole cell; Mt/Chl, isolated mitochondria and chloroplast; Po, isolated peroxisomes. (Scale bars: 1 μm.)     

A novel age-related venous amyloidosis derived from EGF-containing fibulin-like extracellular matrix protein 1

Most intractable tissue-degenerative disorders share a common pathogenic condition, so-called proteinopathy. Amyloid-related disorders are the most common proteinopathies and are characterized by amyloid fibril deposits in the brain or other organs. Aging is generally associated with the development of these amyloid-related disorders, but we still do not fully understand how functional proteins become pathogenic amyloid deposits during the human aging process. We identified a novel amyloidogenic protein, named epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1), in massive venous amyloid deposits in specimens that we obtained from an autopsied patient who died of gastrointestinal bleeding. Our postmortem analyses of additional patients indicate that EFEMP1 amyloid deposits frequently developed in systemic venous walls of elderly people. EFEMP1 was highly expressed in veins, and aging enhanced venous EFEMP1 expression. In addition, biochemical analyses indicated that these venous amyloid deposits consisted of C-terminal regions of EFEMP1. In vitro studies showed that C-terminal regions formed amyloid fibrils, which inhibited venous tube formation and cell viability. EFEMP1 thus caused a novel age-related venous amyloid-related disorder frequently found in the elderly population. Understanding EFEMP1 amyloid formation provides new insights into amyloid-related disorders occurring during the aging process. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.