[Abnormality of cytoskeletons and their phosphorylation in Alzheimer's disease].
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Alzheimer Disease↗
Biomedical subjects
M Takeda
Publications and source records attributed to M Takeda.
The effects of repetitive mild brain injury on cytoskeletal protein and behavior.
The purpose of this study was to examine the hypothesis if repetition of mild mechanical brain injury induces the pathological process related to Alzheimer's disease. After defining the magnitude of the subthreshold brain injury which does not induce brain tissue damage by a single hit, the subthreshold mild impact (1.0 atm) was repeated 7 times every 24 h. One week after the last impact, abnormal accumulation of microtubule-associated protein 2 (MAP2) and phosphorylated neurofilament 200 kD (p-NFH) was observed in neuronal perikarya and dendrites. One month after percussion, the number of MAP2-and p-NFH-positive neuronal perikarya was increased and observed in remote areas including the contralateral cortex and the hippocampus. Tau-1 immunoreactivity was increased in deep cortical neurons of the ipsilateral side after dephosphorylation, indicating the accumulation of phosphorylated tau in neuronal perikarya. The abnormal accumulation of cytoskeletal proteins in neuronal perikarya may be due to impaired axonal transport caused by mechanical brain injury. The behavioral study revealed that after repetitive mild percussion, rats show less efficient habituation to a new environment. It is suggested that the repetition of subthreshold mechanical brain injury may trigger cytoskeletal alteration related to neuronal degeneration.
Alzheimer Disease↗
[Clinical studies of inverted papilloma of the bladder].
Clinical studies were conducted on 9 cases of inverted papilloma of the urinary bladder which were transurethrally resected between August, 1987 and July, 1995 at our hospital, in males between 29 and 81 years of age (mean:58.3). Six of the 9 inverted papillomas were localized at the bladder neck and 3 in the trigone. Cystoscopic examinations revealed that inverted papillomas were divided into two types, one with a thick and short stalk with a smooth surface and the other with a thin and long stalk with/without a partial papillary surface. The majority of the former was located in the trigone and all of the latter cases in the bladder neck, suggesting that the two types occurred at different sites. Pathological examination by Hematoxylin-Eosin staining demonstrated that 5 of the 9 cases were of the trabecular type and 4 were of the grandlar type. Immunohistochemically, none of the tumors were stained with the antiprostatic-specific-antigen antibody revealed. Follow-up periods after the operation were from 12 to 48 months(mean:26.6 months) and no recurrence was observed.
Adult↗
[Clinical and immunological effects of leukapheresis therapy using cotton-wool filter for patients with rheumatoid arthritis].
Remarkable clinical effectiveness of leukapheresis (LP) using a cotton-wool filter as a therapy for patients with rheumatoid arthritis (RA) was previously reported. To study the mechanism and indications for this therapy, 14 patients with RA were treated with this filter 6 times at 2 weeks intervals. The effects on clinical symptoms and subpopulations of peripheral blood mononuclear cells were evaluated on day 0, 3, 7, 14, 42 and 84. The Ritchie articular index, swollen joint counts, Lansbury index and health assessment questionnaire (HAQ), all showed improvements within the first week and the improvements were still observed 3 month later. Improvements in tender joint counts and visual analog pain scale (VAPS) were also observed on day 84. Eight patients showed remarkable improvements (responders) and 6 showed no apparent improvement (non-responders) according to the ACR core set criteria. Responders showed several characteristic features compared to non-responders as follows: the duration of RA was significantly shorter, the anatomical stage was earlier, the positive rate of susceptible HLA-DR4 haplotype associated with Japanese RA (DRB1*0405) was lower, and the proportion of CD4 + Leu8 + lymphocytes and the ratio of CD4+ cells to CD8+ cells (CD+/CD8 ratio) in the peripheral blood were higher throughout the treatment period and increased further even after the course of therapy. The proportion of CD4 + Leu8 + cells was inversely correlated with HAQ and VAPS, suggested that it is critically involved in the mechanism of this therapy. Blood leukocyte analysis at inlet and outlet of the filter showed increase of CD4 +, CD4 + Leu8 + cell percentages and CD4/CD8 ratio. These results suggested that patients with a shorter disease duration, less destruction of the joint, and without susceptible genes were more responsive to this therapy and that the mechanism of clinical improvement of RA by LP with cotton-wool involves immunological modification, such as immunosuppression by CD4 + Leu8 + lymphocytes.
Adult↗
[New surgical technique of anterior decompression for cervical disc disease: vertebral column autograft with the intervertebral disc after anterior cervical decompression].
The authors describe the surgical technique of vertebral column autograft with the intervertebral disc after anterior decompression for cervical disc disease. This series consisted of 41 patients with cervical disc disease suffering from cervical spondylotic radiculomyelopathy. There were 27 men and 14 women, ranging in age from 27 to 72 years (mean age 49 years). 33 patients were operated on at one level and 8 patients at two levels. The average postoperative follow-up period was one year 10 months and ranged from 6 months to 3 years 3 months. The patients were generally allowed out of bed wearing a soft collar within 1 day postoperatively. The collar was used for 2 months after surgery. The postoperative course of all patients was uneventful and neurological symptoms improved. Postoperative X-ray films showed some movement in the operated disc level in all patients. The authors think that this surgical procedure may be suitable for preserving mobility of the spine.
Adult↗
[Hemophagocytosis in a child with paroxysmal cold hemoglobinuria].
A 2-year and 5-month-old boy was admitted to Okaya municipal hospital because of low grade fever and reddish-brown urine soon after an outside walk in November, 1994. Direct Coombs test was negative, but indirect Coombs test positive. Both sugar water test and Ham test were negative. A diagnosis of paroxysmal cold hemoglobinuria (PCH) was made by Donath-Landsteiner (D-L) test which showed the presence of a high amount of anti-P specific IgG and IgM of D-L antibody. Serological tests for syphilis were negative. Cold agglutinin titer and mycoplasma antibody titer was X 128 and X 80, respectively. A bone marrow specimen exhibited pronounced hemophagocytosis. Serum INF-gamma and M-CSF level were normal (less than 5 pg/ml and 1007 units/ml, respectively). These results suggest that hemophagocytosis in this case is not due to hemophagocytic syndrome.
Bone Marrow↗
Cloning of cDNA for asparagine synthetase from rat Sertoli cell.
We have cloned and sequenced cDNA of asparagine synthetase (AS) from rat Sertoli cells. The nucleotide sequence was derived by analysis of cloned cDNA of reverse transcription-polymerase chain reaction (RT-PCR) product that spanned overall the cDNA coding region. The sequence contains three nucleotide differences when compared with that of rat Fao hepatoma cells (Hutson, R.G., and Kilberg, M.S. (1994) Biochem. J. 304, 745-750). Accordingly, amino acid residues Ser at position 330 and His at 491 of Sertoli cells were replaced by Pro and Tyr, respectively, in the sequence of the hepatoma cells. Mutational nucleotide changes may occur during carcinogenesis. The testis contained the most abundant AS mRNA among the tissues studied and others revealed by far a little amount of message. Expressions of AS mRNA in the liver and brain were high in fetal period and reduced rapidly after birth, showing importance of AS in cell proliferation.
Amino Acid Sequence↗
Development and applications of new technology for two-dimensional space-time characterization and correlation analysis of ultraweak biophoton information.
We describe the spatial distribution and temporal correlation analysis of ultraweak biophoton emission based on photoelectron pulse time series and position measurement techniques. Experimental results on the spatio-temporal variation of biophoton emission from soybean seedlings after physical and chemical stimulation to the root tip are analyzed. Our results suggest the potential usefulness of this technique to quantify the transmission mechanisms of biological signals in the living system by measuring the biophoton emission.
Photons↗
[Alzheimer's disease--the molecular biological mechanism and the therapeutic drug design].
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Alzheimer Disease↗
Translocation of loops regulates transport activity of mitochondrial ADP/ATP carrier deduced from formation of a specific intermolecular disulfide bridge catalyzed by copper-o-phenanthroline.
The cross-linking reagent copper-o-phenanthroline complex (Cu(OP)2) specifically caused a decrease in the amount of the 30-kDa ADP/ATP carrier in bovine submitochondrial particles associated predominantly with formation of a 60-kDa protein consisting of a cross-linked dimer of the carrier. However, Cu(OP)2 had no effect on mitochondria. The transport of ADP via the carrier through submitochondrial particle membranes was found to be inhibited in parallel with the progress of intermolecular cross-linking. Analysis of the cross-linked site showed that a disulfide bridge was formed only between two Cys56 residues in a pair of the first loops facing the matrix space. The transport inhibitor bongkrekic acid, which locks the m-state conformation of the carrier, had no effect on disulfide bridge formation catalyzed by Cu(OP)2, but carboxyatractyloside, which locks the c-state conformation by acting from the cytosolic side, completely inhibited the cross-linking. These results show that the ADP/ATP carrier functions as a dimer form, and a pair of the first loops protrudes into the matrix space in the m-state, but possibly intrudes into the membrane in the c-state. Thus, it is suggested that a pair of the first loops acts as a gate and that its opening and closing are regulated by their translocation.
Animals↗
Guanidinoacetic acid (GAA) synthesis in rat tubular suspension as a system for evaluating gentamicin (GM) nephrotoxicity.
Since guanidinoacetic acid (GAA), a precursor of creatine, is synthesized mainly in the proximal tubule of the kidney where gentamicin (GM) nephrotoxicity often occurs, GM-induced renal cell damage was investigated using GAA synthesis in tubular suspension as an indicator. Results obtained were as follows: (1) GAA synthesis was significantly suppressed with 1 mM GM; (2) GM-induced decrease in GAA synthesis was recognized during incubation longer than 15 min; (3) furosemide significantly enhanced the suppression of GAA synthesis by GM. The results obtained parallel with those in the whole animal thus making GAA synthesis in tubular suspension a valid system for evaluating the GM-induced proximal tubular damage.
Animals↗
Clinical efficacy of fluvastatin in the long-term treatment of familial hypercholesterolemia.
The long-term clinical efficacy of fluvastatin was assessed in 24 patients with familial hypercholesterolemia over a total treatment period of 104 weeks. Patients received an initial fluvastatin dose of 20 mg/day for 8 weeks, which was increased to 30 mg/day for a further 16 weeks. From week 24, if serum total cholesterol remained > or = 230 mg/dL, the fluvastatin dose could be increased to 40 or 60 mg/day, as necessary. By the end of treatment, 4 patients were receiving 30 mg/day fluvastatin, 1 patient was receiving 40 mg/day, and 19 patients were receiving 60 mg/day. Serum total cholesterol and low density lipoprotein cholesterol (LDL-C) levels showed a significant decrease from baseline at week 104 (total cholesterol, -26.8 +/- 2.4%; LDL-C, -33.1 +/- 3.3%; p < 0.001). The reductions in total cholesterol and LDL-C were dose-related. Statistically significant (p < 0.05) increases in serum high density lipoprotein cholesterol (HDL-C) were observed at week 24 (12.1 +/- 5.0%) and at week 76 (11.0 +/- 3.3%), although the effect was variable. Nevertherless, at the end of treatment the LDL-C: HDL-C ratio showed a 35% reduction from baseline. Changes in triglyceride levels failed to achieve statistical significance, with a reduction from baseline of -13.9 +/- 7.3% at week 104. Changes in apolipoprotein A-I were variable, with statistically significant (p < 0.01) increases observed at week 24 (7.6 +/- 2.3%) and week 76 (8.4 +/- 2.7%). By contrast, a significant reduction from baseline in apolipoprotein B was achieved by week 12 (-15.0 +/- 2.3%; p < 0.001) and was maintained throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Gastric mucosal protection by YM638, a novel leukotriene D4 receptor antagonist, in rats.
YM638 ([[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl] thio]-1,3,4-thiadiazol-2-yl]thio] acetic acid) is a novel leukotriene D4 receptor antagonist. We investigated the involvement of the leukotriene D4 receptor blocking activity of YM638 in the gastric mucosal protection of this drug in rats. YM638 significantly prevented gastric lesion formation induced by water-immersion restraint stress, indomethacin, absolute ethanol, 0.7 N HCl and the combination of 0.2 N HCl and hemorrhagic shock, with ED50 values of 26.4, 4.1, 4.7, 35.4 and 8.0 mg/kg p.o., respectively. Cetraxate and sofalcone showed inhibitory effects on most of these gastric lesions, but the inhibitory effects of these compounds were much weaker than those of YM638. In contrast, YM638 had no effect on gastric acid secretion and gastric lesion formation in pylorus-ligated rats, or on duodenal lesion formation in cysteamine-administered rats. YM638 competitively antagonized leukotriene D4-induced contraction of the isolated stomach, with a pA2 value of 7.63 +/- 0.18. In anesthetized rats, intravenous YM638 inhibited leukotriene D4-induced aggravation of gastric lesions caused by HCl, and leukotriene D4 and HCl-induced reduction of the potential difference. In addition, oral YM638 significantly increased gastric mucosal blood flow and prevented ethanol-induced increase in gastric vascular permeability. Endogenous prostaglandins, sulfhydryls and nitric oxides were not involved in this inhibitory effect on absolute ethanol-induced gastric lesion. YM638 did not react with the stable free radical 1,1-diphenyl-2-picrylhydrazyl in vitro, indicating that YM638 does not have potential as free radical scavenger. These results suggest that the preventive effect of YM638 on gastric lesions is attributable not only to its leukotriene D4 receptor blocking activity but also to the activation of gastric mucosal defensive mechanisms such as mucosal blood flow and vascular permeability.
Animals↗
Ischaemia-induced change in clathrin preceding delayed neuronal death.
The mechanism underlying the change in clathrin immunohistochemistry preceding delayed neuronal death (DND) was studied in gerbils. The ischaemic change observed with chc5.9 anti-clathrin antibody in hippocampal CA1 was initially ameliorated by pentobarbital, which blocks DND, but 1 day after ischaemia, no change in the immunoreactivity of the SDS-denatured clathrin molecule was detected by Western blotting and no change in the clathrin content in CA1 was detected by SDS-PAGE. No ischaemia-induced change in immunohistochemistry was observed with another monoclonal anti-clathrin antibody, X-22. The above results imply that some modifications that affect the structure of clathrin molecules around the chc5.9 specific epitope may be a crucial step in the course of DND.
Animals↗
Calcium signaling in cultured rat oligodendrocytes.
The syntax of neuronal-glial or axonal-glial interaction is frequently communicated through transient changes in internal calcium (Cai). We examined mechanisms for Cai signaling and intercellular propagation of Cai responses in cultured oligodendrocytes (OLGs) derived from adult spinal cord (SC), postnatal day 21 (P21) SC, and P21 brain. We found that (1) cultured OLGs exhibited a heterogeneous response to norepinephrine, carbachol, ATP, histamine, and glutamate; (2) receptor-mediated Cai increases were derived from both Ca2+ influx and intracellular Ca2+ release; (3) the percentage of responders to neuroligands varied as a function of cell origin; (4) cultured OLGs exhibited a thapsigargin-sensitive, but not a caffeine-sensitive, intracellular Ca2+ pool; and (5) gap junctional contacts between OLGs permitted limited intercellular propagation of mechanically stimulated Cai responses. Receptor-mediated Cai signaling appears to occur not only in cultured OLGs but also in acutely dissociated OLGs. The heterogeneity in Cai responses as a function of cell origin may reflect the existence of OLG subsets or differences in the maturation stage of OLGs.
Adenosine Triphosphate↗
Observations of aggressive, small, flat, and depressed colon cancer. Report of three cases.
Three cases of small, flat, and depressed colon cancers are reported. One lesion is less than 1 cm in diameter with lymphatic invasion in the submucosa; the other measures 0.8 cm in the longest dimension and penetrates through the muscular layers to the subserosa. The third one, 1.2 cm in diameter, has had liver metastasis. The endoscopic appearances of two lesions with a resected specimen are presented in color to demonstrate some difficulties in visualizing these lesions for endoscopists. The biologic aggressiveness of these three lesions appears due to their rapid growth, which is expressed by a high mitotic rate of the cancer cells. Their histogenesis is considered to derive from (1) flat adenoma, from (2) serrated adenoma, and (3) from hyperplastic epithelium (or de novo in origin), respectively.
Adenocarcinoma↗
Focal cortical hypoperfusion in corticobasal degeneration demonstrated by three-dimensional surface display with 123I-IMP: a possible cause of apraxia.
To clarify cortical lesions responsible for apraxia in cortico-basal degeneration (CBD), we reconstructed three-dimensional surface images from single-photon emission computed tomography (SPECT) data with N-isopropyl-p[I-123]-iodoamphetamine in two patients with CBD. Both had limb-kinetic apraxia (LKA) and one also had constructional apraxia (CA). Both showed asymmetrical cortical hypoperfusion in the perirolandic area. The patient with CA had unilateral hypoperfusion in the posterior parietal area. Thus, cortical hypoperfusion in the perirolandic area corresponded to LKA, and that in the posterior parietal area to CA.
Aged↗