Search PubMed⌕ Search

Biomedical subjects

K Tsuzuki

Publications and source records attributed to K Tsuzuki.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Relationship between SPECT and pathological alterations in Alzheimer's disease--a study of a case with left-hemisphere dominant lesions].

123I-IMP SPECT (SPECT) has been widely used in clinical neuropsychiatry for establishing the clinical diagnosis, and evaluating the course of the disease. However, little is known about the significance of alterations in SPECT. In this paper, we present comparative study between alterations in SPECT and neuropathological findings in the case of Alzheimer's disease (AD). The patient, a 59-year-old female, began to show memory disturbance and the left hemisphere disturbances, non-fluent aphasia, but right hemisphere disturbances, constructional apraxia, visuo-spatial dysfunctions were not notable at the early stage. The neuroimaging also revealed left-side dominant cerebral atrophy in MRI and left-side dominant hypoactive regions in SPECT (especially in parietal lobe). Memory disturbance and non-fluent aphasia gradually progressed after admission. Then, mirror phenomenon and Bálint's syndrome appeared at the age of 63 years. In the advanced stage, hypoactive regions in SPECT were expanded into temporal and frontal areas. The laterality observed at the early stage became unremarkable. The patient died from heart failure at 64 years. Pathological diagnosis was AD. Eleven ROI (region of interests) were determined on each hemisphere in transverse SPECT image. We calculated ROI% (each ROI count/ROI count at central cerebellum). Neuronal cell count (NCC) and amyloid beta protein deposited areas (BDA) were estimated using 3 serial sections stained with Nissl's method and immunostained for amyloid using monoclonal antibody raised against synthetic A beta, mcAb 90/12. Digitized images based on photographs were analyzed with NIH-image 1.45. NCC decreased in number in frontal, temporal, and parietal lobes. Significant asymmetrical reduction of NCC (lt. < rt.) was observed in orbital, superior temporal and angular gyri (p < 0.01). BDA in superior parietal lobule, superior temporal gyrus and superior, middle, inferior frontal gyri were larger than those in precentral gyrus and visual cortex. Asymmetry of BDA (lt. > rt.) was significant in middle temporal gyrus (p < 0.01). ROI% at the early stage was correlated with corresponding NCC (r = 0.49, p < 0.05) and BDA (r = -0.55, p < 0.01), but at the advanced stage was not significantly correlated with corresponding NCC (r = 0.26) and BDA (r = -0.20). It is evident that SPECT shows good correlation with clinical features and pathological alterations during the course of AD. Our observations imply that the changes in SPECT usually precede the appearance of the clinical symptoms. SPECT is very sensitive in detecting the functional decline in certain regions of the CNS. In the case of AD, the hypoactive regions in SPECT at the early stage may indicate functional decline of the neuronal cells, and at the advanced stage, these may indicate the degree of pathological changes, especially neuronal loss and amyloid beta protein deposition.

Alzheimer Disease↗
PubMed1996

Random errors in anthropometry.

In order to present basic information on the magnitude of and variance due to the random error in anthropometry, 219 measurement items were taken on 12 subjects twice by the same observer. The precision (i.e., consistency between the repeated measurements) was investigated for these measurement items. The reliability was quantified using mean absolute difference (MAD), technical error of measurement (TEM), and reliability coefficient (R). MAD and TEM are highly correlated with each other and both represent the magnitude of error. They are not correlated with R, which represents the proportion of error-free variance. Larger measurements tend to have absolutely larger but relatively smaller random errors and higher reliability in the size range of 1-10 cm. Imprecision is inherent in anthropometry of the living because of the fact that the human body is not rigid. This may be responsible for the above tendency. Relatively large MAD and low R may be due to small absolute size, landmarks difficult to locate precisely, soft tissue deformation, and the inconsistency of the posture of the subject.

Adult↗
PubMed1995

Amyloid beta protein in rat soleus muscle in chloroquine-induced myopathy using end-specific antibodies for A beta 40 and A beta 42: immunohistochemical evidence for amyloid beta protein.

Previous immunohistochemical studies from this laboratory demonstrated that monoclonal antibodies raised against various regions of amyloid precursor protein (APP) (i.e., N-terminus, amyloid beta protein (A beta), and C-terminus) strongly labeled vacuoles in chloroquine-induced myopathy-affected muscle in rats. In this study, we used antibodies end specific for the A beta 40 and A beta 42 species, and a monoclonal antibody to A beta 1-9 which reacts with APP and A beta. Most vacuoles clearly reacted with anti-A beta 1-9, while about half reacted with anti-A beta 42, and only a few reacted with anti-A beta 40. These results demonstrate that vacuoles in chloroquine-induced myopathy-affected muscle contain cleaved A beta, and that distribution of the two major A beta species is similar to what is observed in A beta deposition in Alzheimer's disease (AD)-affected brain. This provides further evidence that chloroquine-induced myopathy in rats provides a suitable model to understand APP processing into A beta, and the role of APP in terms of the pathogenesis of AD.

Amyloid beta-Peptides↗
PubMed1995

Co-localization of amyloid-associated proteins with amyloid beta in rat soleus muscle in chloroquine-induced myopathy: a possible model for amyloid beta formation in Alzheimer's disease.

Chloroquine, a potent lysosomotropic agent, induces myopathy in experimental animals similar to rimmed vacuole (RV) myopathy in humans. The abnormal accumulation of amyloid beta protein (A beta), which is the invariable pathological alterations in the brains affected by Alzheimer's disease (AD), has been demonstrated in denervated soleus muscle fibers in chloroquine-induced myopathy in rats. In AD affected brains, a variety of additional proteins are associated with the extracellular deposition of A beta, which leads to the intracellular accumulation of neurofibrillary tangles and finally to neuronal death. In this study, we demonstrate that amyloid-associated proteins, alpha 1-antichymotrypsin, apolipoprotein E, SP-40,40 and ubiquitin co-localize with A beta in vacuolated muscle fibers in chloroquine-induced myopathy. There are striking similarities in immunopathology between experimental RV myopathy and AD. Chloroquine-induced myopathy in rats provides a suitable model not only to obtain insight into the basic mechanisms underlying RV formation in muscle, but also to understand amyloid precursor protein processing into A beta, and the role of amyloid-associated proteins in terms of the pathogenesis of AD.

Alzheimer Disease↗
PubMed1995

Twenty-four hour monitoring of blood pressure and heart rate in patients with chronic renal failure or renal transplant recipients: analysis by the cosinor method.

Hypertension is a major problem of patients with chronic renal failure or renal transplant recipients. To clarify the characteristics of blood pressure, heart rate, and circadian rhythms of these patients we used an ambulatory blood pressure monitor (ABPM) for 24 h monitoring and analyzed the data by the cosinor method. In eight chronic renal failure patients without dialysis the midline estimating statistic of rhythm (MESOR) of diastolic blood pressure was higher than in controls, but the MESOR of systolic blood pressure was not. Of 11 patients on dialysis some had hypertension and some had hypotension. In 14 renal transplant recipients, especially those with chronic graft rejection, the MESOR of systolic and diastolic pressures were higher than controls, and the increase of blood pressure MESOR had a significant correlation with the elevation of serum creatinine levels. Circadian rhythms of blood pressure were frequently absent in the patients on dialysis, but circadian rhythms of heart rate were not. The use of an ABPM is a non-invasive method to monitor patients and allowed us to know changes of blood pressure and heart rate in the daytime as well as during the night. For the control of hypertension in chronic renal failure, monitoring with an ABPM seems to provide invaluable information.

Adolescent↗
PubMed1995

Low humoral responses to hepatitis C virus among pediatric renal transplant recipients.

Immunosuppressed patients infected with hepatitis C virus (HCV) are known to have a low prevalence of antibodies to the virus. We examined 12 HCV-infected renal transplant recipients and 18 immunocompetent patients in terms of viral markers. The renal patients had a lower prevalence of anti-C100-3 antibodies and lower titers of anti-p22 than the immunocompetents. Low titers of the antibodies seemed to be characteristic of HCV, because titers of anti-mumps and anti-cytomegalovirus antibodies were the same or even increased. Quantitation of HCV RNA showed approximately 200-fold more copies of mean HCV RNA in the sera of the kidney patients than in the immunocompetents. This indicates that the low humoral responsiveness to HCV is not due to the lower concentration of the virus. Immunosuppressive conditions seemed to suppress anti-HCV production with greater magnitude than other viral antibodies.

Adolescent↗
PubMed1994

Molecular construction of Clostridium botulinum type C progenitor toxin and its gene organization.

The 16S progenitor toxin of Clostridium botulinum type C is made up by conjugation of a neurotoxin with nontoxic components designated as nontoxic-nonHA and hemagglutinin (HA). The HA was found to be composed of subcomponents having 53, 33, 22-23, and 17 kDa molecular masses. Since we previously determined the whole nucleotide sequences of the genes for neurotoxin, nontoxic-nonHA, and HA-33, the cloning and nucleotide sequencing of the genes for the remaining HA subcomponents were performed. Two open reading frames coding for 16.7 kDa (HA-17) and 70.6 kDa proteins were identified. The N-terminal amino acid sequences of HA-53 and HA-22-23 indicated that the 70.6 kDa protein is split into 53 and the 22-23 kDa proteins after translation and that the 22-23 kDa protein consists of at least four proteins showing slightly different molecular weights.

Amino Acid Sequence↗
PubMed1994

Immunohistochemical evidence for amyloid beta in rat soleus muscle in chloroquine-induced myopathy.

Deposition of amyloid beta (A beta) is one of the pathological hallmarks of brains affected with Alzheimer's disease (AD). The accumulation of A beta have been observed in human myopathies with rimmed vacuoles (RVs) which might involve lysosomal function. Chloroquine, a potent lysosomotropic agent, induces muscle pathology in experimental animals similar to myopathy with RV. In this study, we demonstrate, for the first time, immunohistochemical evidence that A beta and cathepsin D, a lysosomal enzyme, accumulate in vacuolated rat soleus muscle due to chloroquine-induced myopathy. These data indicate that lysosomes are important in the metabolism of amyloid precursor protein to generate A beta. This experimental system seems to be useful not only to study basic mechanisms underlying RV myopathy but also to understand processing of amyloid precursor protein to A beta in AD.

Amyloid beta-Peptides↗
PubMed1994

Potentially amyloidogenic fragment of 50 kDa and intracellular processing of amyloid precursor protein in cells cultured under leupeptin.

The principal neuropathological feature of Alzheimer's disease is extracellular deposition of approximately 4-kDa proteinous fragment, designated as beta-amyloid peptides (beta/A4 peptides) derived by proteolytic cleavage from amyloid precursor protein (APP), a large cell-surface receptor-like protein. There has been evidence that APP is proteolytically degraded in the secretory and endosomal/lysosomal pathways. The pathway in which APP is cleaved to generate beta/A4 peptides is still not identified. To clarify the intracellular processing of APP into the generation of beta/A4 peptides, we detected and characterized potentially amyloidogenic or non-amyloidogenic fragments using newly established monoclonal and polyclonal antibodies in the cultured cells with or without leupeptin, potent lysosomal protease inhibitor of lysosome. APP fragments of 50 and 20 kDa containing full-length beta/A4 peptides were identified in the cultured cells. Immunoblot analysis, biochemical study for specific marker enzyme activity of the fractions obtained from subcellular fractionation, sucrose density gradient centrifugation indicated that the 50-kDa APP fragment was produced in the compartment closely related to endosomal/lysosomal system. Our data suggest that the endosomal/lysosomal pathway is involved in the processing and generation of beta/A4 peptides.

Amyloid↗
PubMed1994

U-92032, a T-type Ca2+ channel blocker and antioxidant, reduces neuronal ischemic injuries.

Several diphenylmethylpiperazine derivatives are potential therapeutic agents for prevention of ischemic injuries in the heart and brain, because of their ability to block Ca2+ currents and their antioxidant activity. In this study, the current lead compound, U-92032 ((7-((bis-4-fluorophenyl)methyl)-1-piperazinyl)-2-(2-hydroxyethylamin o)- 4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one), has been compared with flunarizine and nifedipine (well-known T- and L-type Ca2+ channel antagonists, respectively) for their effects on Ca2+ channels in a mouse neuronal cell line, N1E-115 cells, and their ability to preserve the phenomenon of long-term potentiation and to improve neurological symptoms in gerbil ischemic models. U-92032, like flunarizine, blocked transient Ba2+ currents (IBa) through T-type Ca2+ channels with no effect on nifedipine-sensitive non-inactivating currents. Transient IBa was reduced by U-92032 at a constant rate, the magnitude of which depended on the drug concentration, probably because of a time-dependent accumulation of the lipophilic drug in the membrane phase. For instance, the drug at 6 microM reduced IBa by 21% per min and abolished it in less than 5 min, about 3 times faster than flunarizine at the same concentration. Otherwise, U-92032 behaved like flunarizine, showing a use-dependent block without noticeable effects on the current-voltage relationship for transient IBa. Oral administration of U-92032 (1 and 25 mg/kg) or flunarizine (25 mg/kg), but not nifedipine (50 mg/kg), to gerbils 1 h prior to bilateral carotid artery occlusion, preserved long-term potentiation in hippocampal CA1 neurons, which were largely abolished by ischemia without the drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of glutathione depletion on formation of paramagnetic chromium in Chinese hamster V-79 cells.

Incubation of Chinese hamster V-79 cells with either buthionine sulfoximine (BSO) or diethylmaleate (DEM) prior to exposure to Na2CrO4 resulted in a depletion of GSH. ESR study shows that the depletion of GSH by BSO caused an increase in the cellular level of Cr(V) intermediate without affecting the level of Cr(III) complex, whereas the levels of Cr(V) and (III) were both suppressed by the depletion of GSH by DEM. GSH depletion by DEM decreased cellular uptake of chromate more than that by BSO. Glutathione reductase activity in cells, which is capable of reducing Cr(VI), was unaffected by BSO, however a strong inhibition was observed in cells treated with DEM, indicating that DEM affects not only GSH levels but also Cr(VI)-reducing enzyme activity. Thus, the depletion of GSH in cells increases Cr(V) formation, based upon the effect of BSO. The role of intracellular GSH in Cr(VI) reduction is discussed.

Animals↗
PubMed1994

Ion permeation properties of the cloned mouse epsilon 2/zeta 1 NMDA receptor channel.

The heteromeric mouse epsilon 2/zeta 1 N-methyl-D-aspartate (NMDA) receptor was expressed in Xenopus oocytes, and its channel properties were studied using both the outside-out patch-clamp and two-microelectrode voltage-clamp techniques. In the cloned receptor channel, permeation properties of monovalent and divalent cations, and voltage-dependent block by Mg2+ were similar to those reported previously in the native NMDA receptor channels. The sequence of single-channel conductances for alkali metals was Rb+ > Cs+ approximately K+ > Na+ > Li+, whereas the sequence of relative permeabilities was Cs+ > Rb+ > K+ approximately Na+ > Li+. The single-channel conductances measured in isotonic Ca2+, Sr2+ and Ba2+ solutions were almost equal, and approximately one-fifth of the value in the Na+ solution, although the permeabilities for these alkaline earth cations were higher than for Na+. It is likely that Ca2+, Sr2+ and Ba2+ would enter the NMDA receptor channel more easily than Na+, but would bind to a site in the channel more tightly, the net effect being a reduced value of the current.

Animals↗
PubMed1994

Subunit composition at the single-cell level explains functional properties of a glutamate-gated channel.

The diversity of known glutamate-gated channels has been markedly increased by the discovery of multiple subunits and their spliced and edited variants. These subunits can potentially form different oligomeric complexes with diverging properties. A crucial question is therefore to determine the actual subunit composition of naturally occurring glutamate receptors. We have coupled patch-clamp recordings and reverse transcription followed by PCR amplification to correlate the presence of mRNAs for each subunit and the functional properties of native glutamate receptors at the single-cell level. In a homogeneous population of functionally identified hippocampal neurons (type II) in culture bearing a glutamate receptor of the AMPA subtype with a high calcium permeability, we found that, among the multiple subunits, only two, the flop forms of GluR1 and GluR4, were expressed. In particular, GluR2 was never detected. This composition explains the uncommon properties of AMPA receptors in type II neurons.

Animals↗
PubMed1994

DNA single-strand breaks and cytotoxicity induced by chromate(VI), cadmium(II), and mercury(II) in hydrogen peroxide-resistant cell lines.

The induction of cytotoxicity and DNA single-strand breaks by chromium(VI), cadmium(II), and mercury(II) were compared in H2O2-resistant Chinese hamster ovary (CHO(R)) cells and parental (CHO(P)) cells. Using a colony-forming assay, CHO(R) cells were found to be significantly more resistant than CHO(P) cells to the cytotoxicity caused by CdCl2 and HgCl2, but not to that caused by Na2CrO4. However, the DNA single-strand breaks produced by each of these metals were significantly lower in the CHO(R) cells. With respect to chromium reduction, the level of chromium(V) in CHO(R) cells was decreased. The role of intracellular active oxygen in the heavy metal-induced DNA damage and cytotoxicity is discussed.

Animals↗
PubMed1994

Thermal responses affected by different underwear materials during light exercise and rest in cold.

The purpose of this study was to evaluate the effects of two types of underwear materials on thermophysiological responses during rest and light exercise. Two differently moisture-regaining underwear materials were tested: 100% cotton (COTTON) and 100% acrylic (ORLON). Nine female subjects participated in the experiments at an ambient temperature of -10 degrees C. The experiment comprised a 20-min of rest, a 40-min of walking exercise (6 km/h) and a 40-min of recovery. No significant differences could be found in the average values of core temperature, skin and clothing temperatures, amount of non-evaporated and evaporated sweat or subjective ratings of thermal sensations within the two different underwear ensembles. The amount of sweat accumulated into the underwear was very low (3 +/- 1g) and (5 +/- 3g) (mean +/- SE) in COTTON and ORLON, respectively. In both ensembles moisture was transferred towards outer layers of the clothing where the amount of moisture correlated significantly with the total sweat production. In a heavily sweating individual, however, the properties of COTTON underwear, such as wicking ability and high moisture regain, became apparent (accumulated sweat 71g) compared to ORLON (46g). It is concluded that the underwear materials have no significant influence on the thermophysiological responses or subjective sensations under the conditions studied, especially when the sweat rate is low. On the other hand, in individuals with a higher sweating rate the differences between materials may become evident even during light exercise.

Acrylic Resins↗
PubMed1994

Exogenous zinc ion is required for inhibitory activity of botulinum neurotoxin C1 against norepinephrine release and its endopeptidase activity toward substance P.

Botulinum neurotoxin C1 inhibited Ca(2+)-evoked norepinephrine secretion from digitonin-permeabilized PC12 cells. The inhibition by the neurotoxin was dependent on the presence of Zn2+ added exogenously. This zinc-dependent inhibition was neutralized by monoclonal antibodies that recognize the sites close to the putative zinc-binding motif in the light chain. The neurotoxin was found to have an endopeptidase activity toward small peptide, substance P. The presence of exogenous Zn2+ was also indispensable to the full expression of this endopeptidase activity. Thus both the inhibition of neurotransmitter release by the C1 neurotoxin and its endopeptidase activity are dependent on exogenous Zn2+, which suggests a strong link between the two activities.

Adrenal Gland Neoplasms↗
PubMed1994

Oxygen scavengers in simple bone cysts.

Simple bone cyst is a fluid-filled, cystic lesion that occurs in the metaphysis of the long bones of children and adolescents. The chemical characteristics of the cyst fluid of the simple bone cyst are similar to those of serum. The existence of the cyst fluid itself may be an obstacle to cyst healing, and, in part, this may be because the cyst fluid contains bone destructive factors. Oxygen-free radicals, which are cytotoxic and cause connective tissue damage, are known to be generated under ischemic conditions. Blockage to the drainage of interstitial fluid within the metaphysis has been suggested as the possible primary cause of simple bone cyst, thus causing an ischemic state in which free radicals are generated. The precise measurement of free radical levels is difficult to obtain because of their extremely short half-lives. High levels of oxygen-free radicals induce high levels of oxygen scavengers locally to protect cells from the harmful effects of the free radicals. Therefore, the activity of the oxygen scavengers, superoxide dismutase and catalase, was measured in the cyst fluid of 9 cases of simple bone cyst as an indicator of high oxygen-free radical content in the cyst. Serum from the patients with simple bone cyst and joint fluid from patients with osteoarthritis were used for comparison with the intracystic levels of oxygen scavengers. Superoxide dismutase activity was directly measured at room temperature using an electron spin resonance spin-trapping technique with 5,5'-dimethyl-1-pyrroline-N-oxide as a trapping agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗