Search PubMed⌕ Search

Biomedical subjects

T Akashi

Publications and source records attributed to T Akashi.

At least 91 records · Page 5Linked to original sources

Gene expression of CD24 core peptide molecule in developing brain and developing non-neural tissues.

CD24 is a signal transducing molecule on the surface of most human B cells, murine immature T cells, myeloid and erythroid lineage cells. We isolated rat CD24 gene from embryonic brain cDNA library and characterized the gene expression during rat embryogenesis. Rat CD24 cDNA is homologous to murine and human CD24 gene with respect to the structure of signal peptide, N-glycosylation sites, and possible glycosyl phosphatidylinositol (GPI) linker attaching site, suggesting that rat CD24 is a transducing glycoprotein anchoring membrane via GPI linker. In the developing embryo, in situ hybridization analyses revealed that CD24 transcript was detected in primitive ectoderm, mesoderm, and ventral endoderm of day 9 postcoitum (p.c.) embryo. In central nervous systems CD24 transcript was strongly expressed in postmitotic cells of spinal cord, hindbrain, midbrain, and forebrain from day 11 p.c. embryo to day 21 p.c. embryo but was dramatically down regulated in adult brain. Furthermore, expression was also detected in epithelium during development of non-neural tissues, such as intestinal mucosal epithelium, nasal epithelium, ductal epithelium of salivary gland, bronchial epithelium, renal tubular epithelium, and hair follicles. In tooth development, where correct epithelium requires epithelial-mesenchymal interactions, CD24 mRNA was specifically induced in mesenchymal cells differentiating into odontoblast in dental papilla, suggesting the pivotal role of CD24 molecule in cell differentiations in vivo. We suggest that CD24 gene may encode the core peptide molecule of 31 kDa GPI linked molecule which has been known to be important in the migration of neurons on astroglial processes during development.

Amino Acid Sequence↗

Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self-superantigens and processed DR alpha-derived peptide.

We have established a set of transgenic mouse lines in which the HLA-DRA gene was expressed in different cell types. In one line (DR alpha-24), DR alpha E beta b molecules were expressed on thymic medullary and cortical epithelial cells and all lineages of bone marrow-derived antigen-presenting cells (APC) except for thymic macrophages. By contrast, expression of the molecules in another line (DR alpha-30) was found on thymic medullary and cortical epithelial cells but not on bone marrow-derived APC in the thymus and periphery. To evaluate the role of thymic epithelial cells in acquisition of T cell tolerance, comparative analysis of DR alpha-24 and DR alpha-30 was performed. In DR alpha-30, T cells expressing TcR V beta 5 and V beta 11 were eliminated to comparable levels to those in DR alpha-24, suggesting that expression of the DR alpha E beta b molecules on thymic epithelial cells are sufficient for clonal deletion of the self-superantigen-reactive T cells. In addition, CD4+ T cells from DR alpha-30 as well as those from DR alpha-24 were tolerant to DR alpha-derived peptide/I-Ab complex expressed on spleen cells from DR alpha-24 even in the presence of exogenous interleukin-2. These observations suggest that expression of the DR alpha chain in thymic epithelial cells could induce T cell tolerance directed toward naturally processed DR alpha-derived peptide bound to I-Ab molecules, probably via clonal deletion of the self-reactive T cells.

Animals↗

Ultrastructure of proteinase-secreting cells of Candida albicans studied by alkaline bismuth staining and immunocytochemistry.

The ultrastructure of Candida albicans cells induced to secrete extracellular proteinase (EPR) has been studied. Electron microscopy employing alkaline bismuth staining, a method which stains polysaccharides, clearly revealed Golgi-like bodies and secretory vesicles in C. albicans cells. After EPR induction, there was no apparent increase in the number of these structures. Instead, many flocculent granules appeared at the periphery of induced cells. The granules were similar to secretory vesicles in size, but were more irregular in shape. Similar granules were observed in non-induced cells, though less frequently than in induced cells. Brefeldin A, a specific inhibitor of membrane transport in the secretory pathway, caused the accumulation of EPR and Golgi-like bodies in EPR-induced cells, but did not affect the accumulation of the granules. These results suggest that the granules are unrelated to EPR secretion. Electron microscope immunocytochemistry with affinity-purified anti-EPR antibodies showed that the granules in EPR-induced cells were recognized by the antibodies. This recognition was completely inhibited by the presence of glycogen, suggesting that antibodies cross-react with glycogen-like polysaccharides in the granules. Although the location of EPR within the cells remains unclear, the results suggest that EPR might be secreted via the constitutive secretory pathway, and that EPR is glycosylated to give a structure with some similarity to glycogen.

Bismuth↗

Enhancement of extracapsular polysaccharide synthesis in Klebsiella pneumoniae by RmpA2, which shows homology to NtrC and FixJ.

We determined the complete nucleotide sequence of a 2.1-kb HindIII-EcoRI fragment that was cloned from a resident large plasmid of Klebsiella pneumoniae Chedid, a highly virulent and mucoviscous strain of the O1:K2 serotype. This fragment encoded an ability to enhance K2 capsular polysaccharide synthesis in K. pneumoniae, and a 636-bp open reading frame (rmpA2) was found. The 411-bp rmpA reported to be involved in the virulence and mucoid phenotypes of K. pneumoniae by Nassif et al. (Mol. Microbiol. 3:1349-1359, 1989) was a part of rmpA2. Eighty percent homology in nucleotide sequence was found between rmpA2 and rmpA in the corresponding regions. The central domain of the deduced amino acid sequence of RmpA2 showed considerable homology to the central domains of NtrC of K. pneumoniae and Escherichia coli, to which the sigma factor of RNA polymerase binds. The C-terminal domain of RmpA2 also demonstrated considerable homology with the putative helix-turn-helix motifs of LuxR of Vibrio fischeri and FixJ of Rhizobium meliloti. Moreover, RmpA2 also showed some homology in its N- and C-terminal regions to those of RcsA, a transcriptional activator for colanic acid synthesis in E. coli. On the other hand, a sequence upstream of rmpA2 was found to be highly homologous to insertion sequence 3 of members of the family Enterobacteriaceae. Southern hybridization analysis suggested that rmpA2 exists on the large plasmids of all mucoviscous virulent K2 strains but not on those of the slightly mucoviscous avirulent strains. Freeze substitution electron microscopy and fluorescent-antibody staining with anti-K2 serum revealed that K. pneumoniae Chedid has a dense and thick capsule (180 nm) with dense extracapsular substance, whereas K. pneumoniae K2-215, one of the slightly mucoviscous and avirulent strains, has a capsule which is looser and thinner (120 nm) than that of strain Chedid and no extracapsular substance. Introduction of rmpA2 into K2-215 as well as reference strains K. pneumoniae K9 and K72 resulted in a change of the colony phenotype to highly mucoviscous through abundant production of extracapsular substance which reacted with anti-K2, -K9, or -K72, respectively, as did their parental strains. From these results, it is suggested that RmpA2 belongs to the family of transcriptional regulators and confers a highly mucoviscous phenotype on cells of various serotypes of K. pneumoniae by enhancing extracapsular polysaccharide synthesis.

Amino Acid Sequence↗

Ca2+ sensitivity of contractile machinery and Ca2+ handling energy. Simulation.

Myocardial Ca2+ handling during excitation-contraction coupling has been modelled mathematically to gain a better insight into the expectation that Ca2+ sensitization of contractile machinery may save myocardial energy utilization for Ca2+ handling. The basic model of myocardial Ca2+ kinetics and mechanoenergetics involved the sarcoplasmic reticulum (SR), sarcoplasm, troponin C (Tn) and crossbridges (CB). The relations among the released Ca2+ ions from the SR, peak concentrations of sarcoplasmic free Ca2+ ([Ca2+]i) and Ca(2+)-bound troponin ([TnCa]) and peak contractile force were computed, based upon the assumptions that the released Ca2+ ions diffuse as free Ca2+ in sarcoplasm, bind kinetically with Tn with an association rate constant of k1, dissociate from TnCa with a dissociation rate constant of k2, and are sequestered into the SR with consumption of ATP. TnCa was associated with CB cycling to develop force with a set of given on and off rate constants. The association constant Ka (= k1/k2) of TnCa as an index of Ca2+ sensitivity of Tn was varied 32-fold from 0.25 to 8/microM. Results showed that Ca2+ sensitization from a lower Ka level could most sharply decrease the total Ca2+ release required to develop the same contractile force. Thus, it would reduce the total Ca2+ handling energy that the SR uses to maintain the same contractility.

Calcium↗

Left ventricular ORS widening decreases Emax without lowering VO2-PVA relation in dog hearts.

We observed a few rare spontaneous cases of a suddenly widened QRS wave of left ventricular ECG associated with a simultaneous decrease in left ventricular (LV) contractility (Emax, end-systolic pressure-volume ratio) in excised cross-circulated dog heart experiments. The decreased Emax was not associated with a descent of the relation between cardiac oxygen consumption (VO2) and LV systolic pressure-volume area (PVA, a measure of total ventricular mechanical energy). This result is intriguing because ventricular VO2-PVA relation generally changes its elevation in proportion to Emax under various inotropic interventions. We suspected the unusual observation to reflect no change in myocardial contractility despite ventricular asynchrony augmented by an intraventricular conduction defect.

Animals↗

[Physiology of cardiac performance].

We previously proposed i) Emax (end-systolic maximum elastance of the ventricle) as an index of contractility independent of preload and afterload and ii) PVA (systolic pressure-volume area of the ventricle) as a measure of the total mechanical energy generated by the ventricular contraction. Emax is defined as the slope of the end-systolic pressure-volume relation, which is relatively linear within the normal working range of the left ventricle. A working pressure-volume point starts from the end-diastolic pressure-volume curve, comes close to or slightly exceeds the end-systolic pressure-volume line, and returns to the end-diastolic curve. Thus, the end-diastolic and end-systolic pressure-volume curves envelop a family of pressure-volume trajectories of variously loaded contractions in a stable contractility. Emax increases with enhanced contractility and decreases with depressed contractility. PVA is an area between the end-diastolic and end-systolic pressure-volume curves on the origin side of the systolic pressure-volume trajectory. PVA linearly correlates with myocardial oxygen consumption regardless of ventricular loading conditions in a given Emax and this load-independent oxygen consumption-PVA relation is elevated with an enhanced Emax. Consequently, Emax and PVA have proved to be key measures and concepts in the physiology of cardiac performance.

Echocardiography↗

Presenile dementia with progressive supranuclear palsy tangles and Pick bodies: an unusual degenerative disorder involving the cerebral cortex, cerebral nuclei, and brain stem nuclei.

Degeneration of heterogeneous systems in the central nervous system, with widespread distribution of argyrophilic neuronal fibrillary inclusions, was found in a patient with presenile dementia. Atrophy was circumscribed in the frontal and temporal lobes. Neuronal loss was severe in the basal ganglia, subthalamic nucleus, and substantia nigra. Immunocytochemical study using anti-phosphorylated tau and anti-ubiquitin antibodies in conjunction with ultrastructural observations revealed two types of inclusions: neurofibrillary tangles (NFTs) of progressive supranuclear palsy (PSP) in the Edinger-Westphal nucleus, locus coeruleus, cerebellar dentate nucleus, inferior olivary nucleus, and posterior horn of the spinal cord; and Pick bodies (PBs) in the atrophied cerebral cortex and red nucleus. PSP-type NFTs and PBs have been demonstrated in a single case for the first time. Despite their pathognomonic significance in certain disorders, we suggest that these inclusions may reflect a form of cytoskeletal disorganization, which is not entirely restricted to a single disease entity.

Adult↗

[A study to clarify the mechanism of the usefulness of the macrolides--the influence of clarithromycin to biofilm with P. aeruginosa].

Clarithromycin (CAM) was administered long-term to patients with diffuse panbronchiolitis (DPB) to clarify the mechanism of the usefulness of the macrolides (MLs). 1. A tendency for clinical improvement was observed in 17 patients with DPB. Bacteria were eradicated in 7 of 9 patients with P. aeruginosa found in sputum. 2. A biofilm experimental model with P. aeruginosa was found to be destructed through constant contact with CAM and formed into a single cell with a smooth surface. 3. It was believed that the new lesion forming capability of P. aeruginosa that had been in contact with CAM was reduced due to a significant decrease in adherence to tissue. P. aeruginosa was principally eradicated by the host factors. These results suggested that the improvement in the prognosis of DPB with P. aeruginosa in the sputum after adding MLs was closely related to the destructive effect of the MLs on the biofilm.

Animals↗

[The usefulness of the emergency hepatobiliary scintigraphy to rule out acute cholecystitis--43 patients report].

We studied emergency hepatobiliary scintigraphy in the 43 patients to rule out acute cholecystitis. After injection of 185-222 MBq (5-6 mCi) of 99mTc-EHIDA or 99mTc-HIDA, serial static scintigraphic images were obtained up to 7 hours in maximum. Of 43 patients in this study, 20 had a normal scan and finally in all of them cholecystitis was ruled out. Of the 43 patients, 14 had an abnormal scan (nonvisualized gall bladder). In 10 of them the diagnosis of acute cholecystitis was confirmed after emergency cholecystectomy. The other 9 patients of 43 had an incomplete scan mainly due to liver dysfunction. Four of them had acute cholecystitis in the cholecystectomy. These results indicate that acute cholecystitis can be excluded by the findings of gall bladder visualization in hepatobiliary scintigram. We concluded that emergency hepatobiliary scintigraphy is very useful to rule out acute cholecystitis.

Acute Disease↗

[An autopsy case of untreated systemic lupus erythematosus with death from acute pulmonary hemorrhage].

An autopsy case of SLE died from acute and diffuse pulmonary hemorrhage is presented. A 50 year-old woman with SLE was admitted to our hospital because of high fever, butterfly rash, discoid skin lesions and renal dysfunction. She died from acute respiratory failure before initiation of the therapy with corticosteroid. Autopsy findings revealed a massive acute intrapulmonary hemorrhage. Histological study demonstrated a pulmonary arterial vasculitis with prominent fibrinoid necrosis at muscular pulmonary artery. No remarkable deposit of immunoglobulins and complements was found within the alveolar walls and pulmonary vessels by immunofluorescence and electron microscopy. Renal histology revealed diffuse proliferative glomerulonephritis with fibrinoid necrosis, crescent formation and wireloop lesions compatible with type IVb according to the WHO classification. The granular deposit of IgM, C3 and Clq, and electron dense deposit was found by immunofluorescence and by electron microscopy, respectively, in the kidney. The small arteries and veins in other organs, such as liver, spleen, bladder, ovary and rectum also revealed fibrinoid vasculitis. Acute infectious lesion was not observed in any tissue examined. The diffuse pulmonary hemorrhage in SLE could be one of the manifestations of active and severe systemic vasculitis.

Acute Disease↗

[An autopsy case of idiopathic parkinsonism with numerous Lewy bodies in the cerebral cortex--diffuse Lewy body disease].

We report an autopsy case of a 73 year-old female with idiopathic parkinsonism, characterized pathologically by the wide spread appearance of Lewy bodies (LBs) not only in the pigmented neurons in the midbrain and brainstem but also in the cerebral cortex. Initial symptoms at the age of 62 were finger tremor and gait disturbance, which were followed mainly by mental deterioration, such as regression, dependency, auditory hallucination, depression, emotional incontinence, and a personality change. In the terminal stage, nuchal stiffness in extension, one of the hallmarks of progressive supranuclear palsy, and slow and generalized tremor in all 4 extremities were noted. She died of aspiration pneumonia. The brain was somewhat small and weighed 1100 g after the fixation by formalin. Macroscopical findings included mild cerebral atrophy with mild pial thickening both in the frontal and temporal lobes and slight expansion of the ventricular system. Histopathologically, severe loss of neuronal cells in both the pallidum and Luy's body and moderate loss of large cells in the putamen were noted in addition to the typical findings of Parkinson's disease in the substantia nigra and locus caeruleus including neuronal cell loss, depigmentation, and gliosis. These findings in the basal ganglia were more conspicuous than the two controls of classical Parkinson's disease. The distribution, stainability in the routine methods of staining, and shape of Lewy bodies in the cerebral cortex conformed to those of previous reports. The similar case reports in the literatures do not seem to have paid much attention to the findings of the basal ganglia observed in our case.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease.

We investigated sequence variation in the human immunodeficiency virus type 1 (HIV-1) env gene region that encodes the fourth disulfide-bonded domain of the external membrane glycoprotein, gp120, among three HIV-1 isolates from patients with AIDS-related neurologic disease. The sequences of HIV-1 isolated directly from brain tissue, blood cells, and in vitro cell cultures were compared. The results suggest that there may be many closely related HIV-1 genomes of several distinct subtypes in an HIV-1-infected individual. Differences were observed in the frequency distribution of sequence variants obtained from brain versus blood of the same individuals. Overall, the proportion of silent mutations is much lower than expected by random occurrence. Taken together, these results favor the possibility that selective forces may play a role in the tissue distribution of certain HIV-1 strains.

AIDS Dementia Complex↗

Developmental expression of autoimmune target antigens during organogenesis.

A common factor existing among autoimmune target antigens was sought in association with their developmental expression during organogenesis. Autoimmunity against a certain organ was experimentally induced in rats by deliberate immunization with whole tissue extract of the respective organ. Histopathological changes in a target organ of the immunized rats were recorded, and tissue specificity of the raised autoantibodies was immunohistologically examined with tissue sections of normal adult rats. These immune sera were also reacted with tissue sections of a target organ in each stage of organogenesis, and the time of first expression of the target antigen was determined for each immune serum. As a result, induced autoantibodies were directed only to a limited number of tissue antigens, such as thyroid follicular antigens [gestation day 17 (17 GD)], salivary ductal antigens (18 GD), anterior pituitary antigens (21 GD), gastric parietal cell antigens (22 GD), neural myelin antigens (2 days after birth), retinal photo-receptor cell antigens (3 days after birth) and testicular germ cell antigens (4 weeks after birth). They were first expressed on the day indicated in parentheses. Comparing with the development of the immune system, which was monitored by demonstrating CD4- and/or CD8-positive cells in the developing thymus and spleen, a common feature of these potential autoimmune target antigens was found to be that they were expressed either in parallel with, or after, but never before, the development of the immune system. This observation might suggest why only a limited number of self antigens can be autoimmune target antigens among the enormously large number of antigen determinants existing in the whole extract of each organ.

Animals↗

Involvement of the locus coeruleus in Pick's disease with or without Pick body formation.

Brains affected by the fronto-temporal type of Pick's disease were classified into two subgroups according to whether Pick bodies (PBs) were detectable in cerebral cortex (PB-positive group, six cases) or not (PB-negative group, eight cases), and examined neuropathologically. Controls included seven patients with non-degenerative diseases. The neuronal population in the locus coeruleus (LC) was estimated quantitatively in preparations from the middle part of the LC. The data were analyzed statistically by the Mann-Whitney U-test. Histological and ultrastructural studies were also carried out. The following results were obtained: (1) there were no appreciable differences between the PB-positive and PB-negative groups with regard to age at onset, age at death, duration of illness, clinical stage at death, and brain weight; (2) the mean nerve cell counts in the LC were 43.7 +/- 5.2 in the controls, 28.8 +/- 11.7 in the PB-positive group, and 42.9 +/- 7.6 in the PB-negative group. The nerve cell count in the PB-positive group was significantly lower (P less than 0.05) than those in the controls and the PB-negative group; and (3) in each of the PB-positive cases, PBs were disclosed in the LC, in medium-sized melanin-laden neurons and small neurons. PBs were globular or lobulated, and their fine structure was identical to that of typical PBs in the cerebral cortex. In conclusion, PB formation may play an important role in neuronal decrease in the LC of PB-positive cases, whereas the LC may not be affected in PB-negative cases. In this respect, Pick's disease with PB formation appears distinct from that without PB formation.

Aged↗