Search PubMed⌕ Search

Biomedical subjects

K Tsuzuki

Publications and source records attributed to K Tsuzuki.

At least 55 records · Page 3Linked to original sources
PubMed1997

Molecular and physiological diversity of cortical nonpyramidal cells.

The physiological and molecular features of nonpyramidal cells were investigated in acute slices of sensory-motor cortex using whole-cell recordings combined with single-cell RT-PCR to detect simultaneously the mRNAs of three calcium binding proteins (calbindin D28k, parvalbumin, and calretinin) and four neuropeptides (neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, and cholecystokinin). In the 97 neurons analyzed, all expressed mRNAs of at least one calcium binding protein, and the majority (n = 73) contained mRNAs of at least one neuropeptide. Three groups of nonpyramidal cells were defined according to their firing pattern. (1) Fast spiking cells (n = 34) displayed tonic discharges of fast action potentials with no accommodation. They expressed parvalbumin (n = 30) and/or calbindin (n = 19) mRNAs, and half of them also contained transcripts of at least one of the four neuropeptides. (2) Regular spiking nonpyramidal cells (n = 48) displayed a firing behavior characterized by a marked accommodation and presented a large diversity of expression patterns of the seven biochemical markers. (3) Finally, a small population of vertically oriented bipolar cells, termed irregular spiking cells (n = 15), fired bursts of action potentials at an irregular frequency. They consistently co-expressed calretinin and vasoactive intestinal polypeptide. Additional investigations of these cells showed that they also co-expressed glutamic acid decarboxylase and choline acetyl transferase. Our results indicate that neocortical nonpyramidal neurons display a large diversity in their firing properties and biochemical patterns of co-expression and that both characteristics could be correlated to define discrete subpopulations.

Action Potentials↗
PubMed1997

Amyloid beta protein and transthyretin, sequestrating protein colocalize in normal human kidney.

The localization of amyloid beta protein (A beta), A beta 40, A beta 42, and transthyretin (TTR) was investigated immunohistochemically in the autopsied human kidney, using polyclonal antibodies against TTR, A beta and C-terminal end-specific antibodies against A beta 40 and 42. Immunoreactivities of A beta and A beta 40 were found both in the proximal and distal tubular epithelial cells. But the immunolocalization of A beta 40 was observed predominantly in the distal tubules whereas that of A beta 42 was predominantly recognized in the proximal tubules. TTR, sequestrating protein for A beta, was present in the proximal tubules. The mechanism by which A beta does not form amyloid in Alzheimer's disease outside the brain remains unknown. The tubular epithelial cells in the kidney may provide a useful system to shed light on this issue.

Amyloid beta-Peptides↗
PubMed1997

Permeation properties of Na+ and Ca2+ ions through the mouse epsilon2/zeta1 NMDA receptor channel expressed in Xenopus oocytes.

Ion permeation properties of the mouse e2/zeta1 NMDA receptor channel expressed in Xenopus oocytes were studied using the outside-out patch-clamp technique. In symmetrical Na+ solutions, the single-channel I-V relations were almost linear at low electrolyte concentrations, but rectified inwardly for Na+ concentrations above 50 mm. In symmetrical Na+ solutions, the "zero-current conductance" increased with Na+ concentration and saturated according to a hyperbolic curve, the half-maximal saturating activity, KM(Na), being 14.2 mm and the maximal conductance, Gmax(Na), 53.9 pS. When Ca2+ was present with Na+ in the external solution, the single-channel current was lower than in pure Na+, although the reversal potential indicated a higher permeability for Ca2+ than for Na+. Using ion activities, PCa/PNa was found to be about 17. The I-V data were fitted with a model based on the Eyring's rate theory, assuming a one-ion pore with three energy barriers and two sites. The KM(Ca) and Gmax (Ca) were 76.5 microm and 21.2 pS, respectively. According to the estimated rate constants, KM for Ca2+ is mainly determined by the binding strength of a site located 80% away from the channel opening at the external membrane-solution interface, a position similar to that postulated previously for the Mg2+ blocking site.

Animals↗
PubMed1997

Snake coiled fibres in rat soleus muscle in chloroquine induced myopathy share immunohistochemical characteristics with amyloid depositions in Alzheimer's disease brain tissue.

Pathological and immunopathological studies were carried out on snake coiled fibres (SCF) which occurred in affected soleus muscle in chloroquine treated rats. The SCF began to appear in denervated soleus muscle by 8 days after chloroquine injection. By day 14, typical SCF were observed with an unusual swirling pattern of the myofibrils, presenting a bizarre appearance. By day 21 or later, the SCF became less remarkable, and were fragmented and broken apart to form large vacuoles. Immunopathological studies demonstrated that the amyloid beta (A beta) and N and C-terminal regions of amyloid precursor protein (APP), and the amyloid associated proteins tested, apolipoprotein E (apoE), SP-40,40, alpha 1-antichymotrypsin (alpha 1-ACT), and ubiquitin, which are known to be components of amyloid depositions found in Alzheimer's disease (AD) affected brains, were present in the SCF. ApoE, SP-40,40, alpha 1-ACT, and ubiquitin are induced following certain cell challenges (e.g. heat shock, various drugs and injury). The significance of APP, A beta, and amyloid associated proteins are discussed in respect to snake coiled fibre formations in chloroquine rat myopathy and in the amyloidogenesis of AD.

Alzheimer Disease↗
PubMed1997

Epitope regions in the heavy chain of Clostridium botulinum type E neurotoxin recognized by monoclonal antibodies.

Seventeen monoclonal antibodies (MAbs) were previously established against the heavy chain (Hc) of botulinum type E neurotoxin in BALB/c mice immunized with the type E toxoid. Five MAbs (LE15-5, LE34-6, EK19-7, EK21-4, and AE27-9) showed toxin-neutralizing activity in mice. Two of the five MAbs, EK19-7 and EK21-4, recognized the regions located at amino acid positions 731 to 787 and 811 to 897, respectively. One of the remaining three antibodies (LE34-6) reacted with the amino acid sequence VIKAIN, at amino acid positions 663 to 668, closed by the ion channel-forming domain. It is suggested that the ion channel-forming domain may also be associated with the blocking of acetylcholine release. Furthermore, the amino acid sequence YLTHMRD within 30 residues of the C-terminal region of the Hc component seemed to be recognized by LE15-5. It has been reported that the binding domain of the type E toxin is located on the C-terminal half of the Hc component. Therefore, the neutralizing activity of LE15-5 antibody may be attributed to its ability to block the binding of neurotoxin to the receptor of target cells.

Amino Acid Sequence↗
PubMed1997

Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism.

Familial hypocalciuric hypercalcemia (FHH) is characterized by lifelong asymptomatic hypercalcemia without PTH hypersecretion and is inherited as an autosomal dominant trait with near 100% penetrance. In contrast, neonatal severe hyperparathyroidism (NSHPT) is a life-threatening disorder characterized by marked hypercalcemia and PTH hypersecretion. FHH/NSHPT results from inactivating mutations of the human calcium-sensing receptor (Casr) gene on chromosome 3q13.3-24. Nearly 30 different mutations of the Casr gene associated with FHH/NSHPT have been reported previously. In this report, genetic analysis of 1 Japanese NSHPT family revealed 2 novel mutations at codon 185 (CGA-->TGA/Arg-->Ter) in exon 4 of the Casr gene and at codon 670 (GGG-->GAG/Gly-->Glu) in exon 7. The Arg185Ter change was shown to occur in the proband's unaffected father and paternal grandmother as well as in the proband. The other mutation in exon 7 was shown in the proband's unaffected mother of Philippine origin as well as in the proband. This family is the first case of manifestation of more than 1 mutation in a proband's chromosomes; 1 mutation was obtained from the unaffected father, and the other was from the unaffected mother. Our observations have given us important keys to help elucidate the structure-function relationships of the Casr.

Arginine↗
PubMed1997

A prospective trial of steroid cessation after renal transplantation in pediatric patients treated with cyclosporine and mizoribine.

We conducted a multi-center prospective study to evaluate the safety and efficacy of steroid withdrawal after renal transplantation in children. In 52 children (51 living-related donor transplants and 1 cadaver donor transplant), immunosuppressive therapy was started with cyclosporine (CyA), mizoribine (MZ), methylprednisolone (MPL) and anti-lymphocyte globulin. Administration of MPL was reduced to alternate days more than 6 months after transplantation, and attempts were made to withdraw it. Acute rejection was noted in 19 patients (36.5%) by 1 month after transplantation. The whole-blood CyA trough level using monoclonal antibody was 175.0+/-17.0 ng/ml in patients who developed acute rejection and 282.0+/-25.3 ng/ml in those who did not show acute rejection (p<0.01). During the 37 attempts at alternate-day MPL administration, clinical acute rejection was observed in only 1 patient and chronic rejection in 3. During 10 attempts to withdraw MPL, acute rejection was noted in 3 patients, but graft function recovered to the pre-rejection level after treatment of the acute rejection. At the last observation, graft function was lost in 3 patients, 22 were receiving MPL on alternate days, and MPL had been withdrawn from 7 for a mean period of 16.7 months. The survival rate of the patients and the grafts was 100% and 94% after an average follow-up period of 4 years. Evaluation of growth showed catch-up growth in all patients during the withdrawal period.

Anti-Inflammatory Agents↗
PubMed1997

[Recent advances in Alzheimer's disease research--amyloid precursor protein trafficking, processing, and mutations in Alzheimer's disease linked genes].

Recent advances in Alzheimer's disease (AD) research were briefly reviewed. The AD affected brain is characterized by numerous amyloid plaques, neurofibrillary tangles, and neuronal losses. The amyloid is composed of amyloid beta peptide (A beta), a 40-42 amino acid fragment of large membrane protein, amyloid precursor protein (APP). A beta is cleaved by proteolytic enzyme, beta, and gamma secretase yielding N and C terminus of the A beta. Considerable effort has been directed to identify these enzymes, and to find the intracellular compartments where A beta is generated. Endosome, lysosomal pathway, or related acidic compartment is one of the candidates for A beta generation. Biochemical and immunopathological data implicate that A beta 42 is more important than A beta 40 in the pathogenesis of AD. On the other hand, many missence mutations in APP gene and other gene, S182 (presenilin1), and STM2 (presenilin2) were identified in familial AD. Neuropathology in these FAD appear basically quite similar, and AD is regarded as cerebral A beta amyloidosis. It was established that missense mutations in the genes encoding APP, presenilin1, and presenilin2, all treated APP processing, leading to increased production of A beta 42. AD amyloid is composed of many other proteins than A beta, designated as amyloid associated proteins, It should be a key issue to determine the precise mechanism, by which A beta is generated, and the alteration of APP trafficking resulting in increased A beta 42 generation with these mutant genes.

Alzheimer Disease↗
PubMed1997

[Binocular functions in amblyopia and strabismus].

Regarding the changing trends in the concept, definition, etiological classification, and criteria for diagnosis of amblyopia, we reviewed a total of 4,693 cases of amblyopia seen during the past 37 years. The amblyopia was divided into four types: strabismic, anisometropic, ametropic, and form vision deprivative. There was a definite trend for the incidence to decrease and for the diagnosis to be made during earlier age in recent years. Although favorable recovery of visual acuity is obtained after treatment of amblyopia and strabismus, there are difficulties in obtaining good binocular functions in early-onset amblyopia and strabismus. This feature was evaluated in regard to motion perception asymmetry (MPA) and binocular depth from motion (DFM). Many cases of early-onset amblyopia and strabismus showed no disparity stereopsis, or position stereopsis, in spite of the presence of DFM. The MPA appeared to be closely related to early-onset esotropia regardless of age, while it disappeared and motion perception became symmetric 4 to 5 months after birth in normal infants. The DFM seemed to play an important role in maintaining good motor alignment for several years after surgery. I developed a checkerboard pattern stimulator in 1978. This method proved to be useful in developing binocular functions and motor alignment by applying simultaneous bifoveolar stimulation and anti-suppression. Extensive exposure to the stimulation was essential for therapeutic success.

Adolescent↗
PubMed1996

Distribution of neurones expressing inwardly rectifying and Ca(2+)-permeable AMPA receptors in rat hippocampal slices.

1. Current-voltage (I-V) relationships and Ca2+ permeability of receptor channels activated by bath application of kainate, a non-desensitizing agonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were examined in various types of neurones in hippocampal slices of 5- to 13-day-old rats by using the tight-seal patch clamp recording technique. 2. Three types of responses were observed: type I response with outwardly rectifying I-V relationship, type II response with I-V relationship of marked inward rectification, and intermediate response with I-V relationship of weaker inward rectification. Neurones with type I, type II and intermediate I-V relationships of kainate responses were referred to as type I, type II and intermediate neurones, respectively. 3. Permeability of Ca2+ ions was estimated by the reversal potential of kainate response in the outside-out patch in Na(+)-free extracellular solution containing 100 mM Ca2+. The reversal potentials were -44.4 +/- 14.0 mV (mean +/- S.D.) for type I (n = 7), +11.8 +/- 3.6 mV for type II (n = 5), and -8.7 +/- 7.4 mV for the intermediate neurones (n = 7). The values of PCa/PCs, the ratios of the permeability coefficients of Ca2+ and Cs+, estimated according to the constant-field equation were 0.08 for type I, 1.71 for type II, and 0.50 for the intermediate neurones. 4. Type II and intermediate responses were observed mainly in non-pyramidal neurones in various areas of the hippocampus, most frequently observed in the stratum molecular of the dentate gyrus and in the stratum radiatum and the stratum lacunosum-molecular of both the CA1 and CA3 regions. Both type II and intermediate neurones stained with biocytin had round- or ellipsoidal-shaped somata and issued divergent axonal projections to the surrounding structures. 5. Excitatory postsynaptic currents (EPSCs) recorded in type II neurones had 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive fast and D-2-amino-5-phosphonovalerate (APV)-sensitive slow components. The I-V relationship of the fast component showed a strong inward rectification, indicating that inwardly rectifying AMPA receptors are involved in excitatory synaptic transmission.

2-Amino-5-phosphonovalerate↗
PubMed1996

Effects of the thermal conditions of the dressing room and bathroom on physiological responses during bathing.

The effects of the thermal conditions of the dressing room and bathroom on the physiological responses during bathing were assessed. Six female students participated in this experiment. Three climate chambers were used as a living room, a dressing room and a bathroom. The living room was thermoneutral and maintained at 25 degrees C, while the thermal conditions of the dressing room and bathroom were as follows: (A) cold (10 degrees C), (B) cool (17.5 degrees C) thermoneutral (25 degrees C). The subjects wore standard clothing (0.65 clo). Heart rate (HR), blood pressure, rectal (Tre) and skin temperature, and subjective thermal sensation were recorded. 1) Marked increases in systolic blood pressure (SBP) after undressing and redressing in the dressing room and during washing were observed under the cold conditions. 2) A significant negative correlation was found between the dressing room temperature and increased SBP compared to before bathing (r = -0.684, p < 0.01, n = 18). 3) After exposure, mean skin temperature (Tsk) showed marked differences among the three conditions despite the rest taken under the same thermal conditions. 4) A significant negative correlation was found between Tsk and the increase in SBP of after undressing relative to that before bathing (r = -0.695 p < 0.01, n = 18). These findings suggested that 25 degrees C was the most appropriate temperature for the bathroom and dressing room, since the increase in blood pressure was minimum and subjective thermal sensation was neutral (neither cool nor warm) to warm under this thermal condition, and 17.5 degrees C at which the increase in blood pressure was within the physiological fluctuation range (+/- 10 mmHg) is the minimum tolerable temperature.

Adult↗
PubMed1996

[Aging brains and the dementias].

Dementia has been defined generally as an acquired persistent impairment of intellectual function caused by organic brain diseases. The rapidly increasing incidence of dementias has been claimed on the basis of epidemic studies in Japan as well as in Western developed countries. These observations are justified by the facts that most dementias are found in people over the age of 65 years, and that the elderly population is increasing rapidly resulting in both absolute numbers and percentage of the population. In Japan, it is estimated that 1.5 million of demented persons are present. The purpose of this paper is to describe clinical manifestations and morphological alterations of aged and demented individuals, diagnostic process to differential diagnosis to provide knowledgeable approach to management, and adequate care of the demented individuals. In aged brain, there are a variety of morphological changes. Some of these are usually observed in aged brains; atrophy of the brains, loss of neurons, accumulations of lipofuscin. Others observed in pathologically aged brains, or accelerated aging brains are Alzheimer's neurofibrillary tangles, senile plaques, and granulovacuolar degeneration. Psychiatric manifestations associated with aging and dementing diseases are described. It should be realized that clinical manifestations of the demented reflect primarily the topography of the organic lesions in the brain, and functional alterations, and are influenced by psychological and socio-environmental factors.

Aging↗
PubMed1996

[Biological characteristics of amyloid precursor protein and Alzheimer's disease].

Recent advances in Alzheimer's disease (AD) research were briefly reviewed. AD is the most common cause of progressive intellectual decline in the aged in the Western world and also in Japan. The AD-affected brain is characterized by numerous amyloid plaques, neurofibrillary tangles, and neuronal losses. The amyloid deposition is considered to be more important because it appears first, and is followed by NFTs. The amyloid is composed of amyloid beta peptide (Abeta), a 40 approximately 42 amino acid fragment of the large membrane protein, amyloid precursor protein (APP). Abeta is cleaved by the proteolytic enzymes, beta, and gamma secretase. Considerable effort has been directed to identify these enzymes, and to find the intracellular compartments where Abeta is generated. The lysosome, or related acidic compartment is one of the candidates. The N and C terminis of the Abeta is known to vary slightly. Biochemical and immunopathological studies implicate that Abeta42 is more important than Abeta40 in the pathogenesis of AD. On the other hand, many missense mutations in APP gene and other genes, e.g. S182, and STM 2 have been identified in familial AD. Neuropathologically, AD is regarded as cerebral Abeta amyloidosis. The AD amyloid is composed of many proteins other than Abeta, designated as amyloid associated proteins. These proteins may play important roles in amyloid formation, since Abeta itself is soluble. Transgenic mice and chloroquine myopathy rat are available as animal models for AD. Elucidation of the roles of these missense mutations, and amyloid associated proteins in the cascade of AD, may provide a breakthrough to therapeutics for AD.

Alzheimer Disease↗