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Biomedical subjects

Y Hatakeyama

Publications and source records attributed to Y Hatakeyama.

At least 37 records · Page 2Linked to original sources
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

[The disturbance of reversible operation in space in the early stage of Alzheimer's disease].

Constructional apraxia is one of the neuropsychological findings frequently observed in the early stage of the Alzheimer's disease, which may result from the visuo-spatial disturbances. The visual space consists of a variety of visual information processing, viewer-centered coordinate system, objects-centered coordinate system, integration of both coordinate systems, and verifying visual representation with the knowledge in the memory. The reversible operation in space, or mental rotation appears to play an important role in visuo-spatial functions, which refers to the operation of the visual representation at one orientation in viewer-centered coordinate system to construct the representation in object-centered coordinate system so that one can look like if it were presented at another orientation. To the present, little is known about reversible operation or mental rotation in patients with Alzheimer's disease. In this present paper, we attempted to investigate the ability of reversible operations in space so as to understand the mechanisms underlying constructional apraxia, or visuo-spatial disturbances in the early stage of Alzheimer's disease. The subjects were 12 patients with Alzheimer's disease in early stage (AD group), 12 patients with multi-infarcts dementia as disease control (MID group), 12 age matched persons as healthy control (HC group). In perspective taking tasks, that requires the subjects to imagine the spatial arrangement of the objects at the different view points from the subjects' one, AD group showed more severe deficits than MID group and HC group. Moreover, in a task that the subjects were asked to assume the photo-angle of the photograph taken of the model which was in front of them, AD group was imparied compared to the control groups. These disturbances were closely associated with deficits in Block Design test of WAIS. These results clearly demonstrate that the patients with Alzheimer's disease have disturbance in reversible operation in space and that the disturbance may be responsible for visuo-spatial dysfunctions, not only the constructional apraxia, but also a variety of performance deficits in the early stage of Alzheimer's disease.

Aged↗
PubMed1996

A pyrroline glucoside ester and steroidal saponins from Lilium martagon.

A new phenylpropanoid ester of a pyrroline derivative and two new steroidal saponins were isolated from the fresh bulbs of Lilium martagon, along with several previously known compounds. The structures of the new compounds were determined by spectroscopic data, hydrolysis, and by comparison with spectral data of known compounds to be (-)-5-hydroxy-3-methyl-3-pyrrolin-2-one 5-O-(6-O-p-coumaroyl-beta-D- glucopyranoside), (25S)-spirost-5-ene-3 beta,17 alpha, 27-triol 3-O-[O-beta-D-glucopyranosyl-(1-->2)-O-beta-D-glucopyranosyl- (1-->4)-beta-D-glucopyranoside] and (25S)-5 alpha-spirostane-3 beta,17 alpha,27-triol 3-O-[O-beta-D-glucopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->4)-bet a-D- glucopyranoside], respectively. Lilium martagon crosses well with L. hansonii to produce a valuable garden hybrid lily. In this study, the secondary metabolites of L. martagon were revealed to be closely related to those of L. hansonii, giving a good example of the correlation between the secondary metabolites and cross-compatibility.

Carbohydrate Sequence↗
PubMed1996

Implication of sensory neurons in the diverse mechanisms of adaptive cytoprotection in the rat stomach.

Adaptive cytoprotection is mediated by diverse mediators and mechanisms. We investigated the implication of capsaicin-sensitive afferent neurons in the adaptive cytoprotection in the rat stomach, taking special notice of nitric oxide, prostaglandins and luminal dilution. Sensory deafferentation abolished the protective effect of capsaicin against 0.6 N HCl-induced gastric injury but not the indomethacin-resistant or NG-nitro-L-arginine-resistant adaptive cytoprotection conferred by 0.1 N NaOH. Nor did it attenuate the protection by 0.35 N HCl which accompanied luminal dilution. These findings suggest that certain mild irritants do not require sensory neurons to provide nitric oxide- and prostaglandins-mediated adaptive cytoprotection and, furthermore, that capsaicin-sensitive afferent neurons are not crucial, either, so long as there is a contribution of luminal dilution in the adaptive cytoprotection.

Animals↗
PubMed1996

Detection of HIV-1 and HIV-2 antibodies among Chlamydia trachomatis infected pregnant women in Japan.

An anonymous unlinked HIV antibody test was conducted on 1632 Chlamydia trachomatis (C. trachomatis) antibody positive women from 10 institutes of 7 prefectures in Japan. All the sera were negative for both HIV-1 and HIV-2 antibodies. The result may support the suggestion that HIV prevalence is low among general population in Japan. Such a test as this study will be useful not only for developing a reliable HIV surveillance system but also for the study of sexual behavior of general population, since C. trachomatis infection is sensitive to reflect sexual contact.

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↗
PubMed1995

Luminal dilution caused by certain mild irritants and capsaicin contributes to their gastric mucosal protection.

We have recently shown that certain mild irritants caused the increase in fluid volume in the rat stomach. The present study was conducted to investigate 1) whether standing fluid in the gastric cavity can prevent gastric mucosal injury caused by 0.6 N HCl and 2) the mechanisms by which certain mild irritants increase the gastric fluid volume. One milliliter of water administered immediately before irritants greatly inhibited gastric lesion formation. Sodium chloride and capsaicin induced a profound enhancement of gastric fluid volume, as acid mild irritants did also. Sensory denervation completely abolished the volume increase caused by capsaicin but hardly influenced that caused by mild irritants. Capsaicin increased the amount of Evans blue in the gastric fluid, but mild irritants did not. On the other hand, HCl and capsaicin significantly inhibited the emptying of phenol red. From these results, we conclude that mild irritants and capsaicin can induce volume increase that by itself is enough to afford protection through luminal dilution. Capsaicin but not mild irritants requires sensory neurons to increase the gastric fluid volume. Certain mild irritants may provide a fluid pooling effect partly by inhibiting gastric emptying.

Animals↗
PubMed1995

Change in membrane permeability induced by amyloid beta-protein fragment 25-35 in brain neurons dissociated from rats.

Effects of amyloid beta-protein fragment 25-35, A beta P(25-35), on the membrane permeability of organic molecules were examined in the brain neurons dissociated from rats by using an argon laser (equipped in flow cytometer and laser microscope) and a combination of two fluorescent dyes, fluo-3-AM and ethidium bromide. A beta P(25-35) at concentrations of 1 microM or greater induced both leakage of fluo-3 from the neurons and permeation of ethidium across the membrane in a dose-dependent manner, although both dyes are highly impermeant to the intact plasma membrane. Thus, A beta P(25-35) seems to increase not only membrane permeability of inorganic ions such as Ca2+, Na+ and K+, as previously suggested, but also that of organic molecules. Therefore, the brain neuron membrane is suggested to lose its integrity in the presence of A beta P(25-35) that leads to neuronal death.

Amyloid beta-Peptides↗
PubMed1994

Flow cytometric analysis on cytotoxic action of amyloid beta protein fragment 25-35 on brain neurons dissociated from the rats.

Effects of amyloid beta protein fragment 25-35, A beta P(25-35), on membrane permeability and cell viability were examined in the brain neurons dissociated from the rats using a flow cytometer and two fluorescent dyes, fluo-3 to monitor intracellular Ca2+ concentration ([Ca2+]i) of neurons and ethidium which is impermeant to membranes of intact neurons to stain dead and dying neurons. A beta P(25-35) augmented fluo-3 fluorescence of some neurons at concentrations greater than 1 microM, indicating an increase in [Ca2+]i although other neurons (about 80% of total neurons) did not respond to A beta P(25-35) even at 10 microM. A beta P(25-35) at 1 microM or greater increased dose-dependently the number of ethidium-stained neurons, suggesting a dose-dependent increase in number of dead and dying neurons. Results suggest that A beta P(25-35) increases the membrane permeability of brain neurons, resulting in a destabilized intracellular homeostasis that leads to neuonal death.

Amyloid beta-Peptides↗
PubMed1994

Effect of N,N-diethyldithiocarbamate on ionomycin-induced increase in oxidation of cellular 2',7'-dichlorofluorescin in dissociated cerebellar neurons.

Effect of N,N-diethyldithiocarbamate (DDC), an inhibitor for cytosolic superoxide dismutase, on an ionomycin-induced increase in oxidative metabolism was examined in cerebellar neurons dissociated from the rats, using a flow cytometer and 2',7'-dichlorofluorescin diacetate and fluo-3-AM, fluorescent dyes for intracellular hydrogen peroxide and Ca2+, respectively. DDC reduced the ionomycin-induced augmentation of 2',7'-dichlorofluorescin fluorescence in a dose-dependent manner. DDC did not affect cellular content of 2',7'-dichlorofluorescin and ionomycin-induced increase in intracellular Ca2+ concentration. Results indicate that ionomycin increases the formation of superoxide anion in brain neuron.

Aniline Compounds↗
PubMed1994

Phenthoate metabolites in human poisoning.

Five metabolites were detected in the plasma and urine of a patient following ingestion of the organophosphate insecticide, phenthoate. Intact phenthoate was detected only in gastric lavage fluid. After methylation of acidic extracts of plasma and urine, phenthoate acid, demethyl phenthoate, demethyl phenthoate oxon acid, demethyl phenthoate S-isomer, and demethyl phenthoate acid S-isomer were identified with synthesized phenthoate analogues by gas chromatography and gas chromatograph-mass spectrometry. The main metabolites were phenthoate acid and demethyl phenthoate oxon acid. Although demethyl phenthoate oxon acid was a significant metabolite, no phenthoate oxon, phenthoate oxon acid or demethyl phenthoate oxon were detected. If the oxon was formed in the patient, it may have been rapidly degraded by carboxylesterase or glutathione transferase to demethyl phenthoate oxon acid.

Chromatography, Gas↗
PubMed1994

[An experimental study of the efficacy of platelet aggregating inhibitor on hepatic metastasis].

To investigate whether OKY-046 (an inhibitor of thromboxane A2 synthetase) and TCV-309 (an antagonist of platelet activating factor) can inhibit VX-2 tumor metastasis, the following studies were performed. Study 1 animal experiment: VX-2 tumors were inoculated and OKY-046 or TCV-309 was administered into the portal vein with or without combination of adriamycin (ADR). The number of tumor nodules on the whole liver surface were counted at three weeks after tumor cells inoculation. The combination of OKY-046 and ADR significantly reduced the number of tumor nodules compared to control and TCV-309. Study 2 in vitro experiment: Human breast cancer cells (MCF-7) overlayed confluently cultured human endothelial cells (HUVEC) in vitro with or without OKY-046 and TCV-309 for 3 days; MCF-7 cells invaded the endothelial cells and built-up colonies. The number of colonies built up were counted. OKY-046 significantly decreased the number of colony formations, but TCV-309 did not. These results suggest that OKY-046 has an inhibitory effect on extravasation of tumor cells.

Animals↗
PubMed1994

[Efficacy of intrahepatic arterial chemotherapy to prevent recurrence of residual liver in metastatic liver cancer patients after hepatectomy].

Five-year overall survival rates in 17 cases who underwent the hepatectomy for metastatic liver cancer from digestive tract averaged 43%. Postoperative intrahepatic arterial infusion in combination with Farmorubicin and 5-FU was performed in 9 cases (i.a group). Survival and recurrence rate on cases (i.a group) were compared with that of 8 cases without chemotherapy (control group). The 5-year survival rate was superior in the i.a group to that in the control group. There was no residual liver recurrence in the i.a group, but two cases had recurrence in the residual liver in the control group. These results suggest that the post-hepatectomized intrahepatic arterial infusion of anticancer drugs is useful to prevent recurrence in the residual liver and may prolong the survival time of patients with metastatic liver cancer from GI tract.

Aged↗
PubMed1994

[Studies on compensation in medicinal plants. Compensative effects in leaves of Papaver somniferum L. on photosynthetic and transpiration rates].

To investigate compensative effects in leaves of Papaver somniferum L., the relation between photosynthetic rate and light density and leaf temperature, and the influences on photosynthetic and transpiration rates of removal of the three upper leaves were examined under field conditions. The light saturation point in leaves of P. somniferum was about 900 micro molm-2sec-1 and the photosynthetic rate at the light saturation point was about 13.5 micro molm-2sec-1 between 23 and 28 degrees C in leaf temperature. The light compensation point in leaves was nearly 50 micro molm-2sec-1. The influence of leaf temperature on photosynthetic rate was significant, so that the latter showed a remarkable decrease when the leaf temperature was above 30 degrees C. When the three upper leaves were removed, the photosynthetic and transpiration rates in the 4th leaf tended to increase as compared with control level, although the increases were not significant.

Light↗
PubMed1993

Establishment and characterization of a monoclonal antibody recognizing the Dewar isomers of (6-4)photoproducts.

We established a monoclonal antibody (DEM-1) that recognizes UV-induced DNA damage other than cyclobutane pyrimidine dimers or (6-4)photoproducts. The binding of DEM-1 antibody to 254 nm UV-irradiated DNA increased with subsequent exposure to UV wavelengths longer than 310 nm, whereas that of the 64M-2 antibody specific for the (6-4)photoproduct decreased with this treatment. Furthermore, the increase in DEM-1 binding was inhibited by the presence of the 64M-2 antibody during the exposure. We concluded that the DEM-1 antibody specifically recognized the Dewar photoproduct, which is the isomeric form of the (6-4)photoproduct. The DEM-1 antibody, however, also bound to DNA irradiated with high fluences of 254 nm UV, suggesting that 254 nm UV could induce Dewar photoproducts without subsequent exposure to longer wavelengths of UV. Furthermore, an action spectral study demonstrated that 254 nm was the most efficient wavelength for Dewar photoproduct induction in the region from 254 to 365 nm, as well as cyclobutane dimers and (6-4)photoproducts, although the action spectrum values in the UV-B region were significantly higher compared with those for cyclobutane dimer and (6-4)photoproduct induction.

Animals↗
PubMed1993

[Prevalence of bacterial pathogens and antimicrobial susceptibility: a multicenter study in Akita prefecture].

We report the prevalence of bacterial pathogens isolated from various clinical specimens in 17 medical centers in Akita during the period of December 1990 to February 1991, and their antimicrobial susceptibility. The results were as follows: 1. The total number of isolates was 8,929 and common bacteria were Staphylococcus aureus (18.7%), Pseudomonas aeruginosa (11.8%), Escherichia coli (10.1%), coagulase negative staphylococcus (6.7%) and Enterococcus faecalis (5.0%). This is similar to our previous result which was reported in the same season in 1987. 2. S. aureus was a common isolate from sputum, throat swab, pus, and blood. 53% of isolated S. aureus were methicillin-resistant. Arbekacin (ABK) had a high degree of activity (99%) against methicillin-resistant S. aureus (MRSA). Minocycline (MINO) retained activity against 70% of MRSA strains, and quinolones only 20%. 3. P. aeruginosa and E. coli were frequently found in urine from the patients in the small hospitals. More than 80% of the P. aeruginosa strains were sensitive to imipenem (IPM), cefsulodin (CFS) and amikacin (AMK). The susceptibility of P. aeruginosa to ceftazidime (CAZ) and piperacillin (PIPC) had been decreasing for the last 3 years. 4. CNS were frequently found in blood, pus, and pleural effusion from the patients in the large hospitals. The isolates were resistant to most antibiotics. 5. Enterococcus was common isolates from urine and ascites, the susceptibility to cephem was low. 6. We conclude that attention should be specially paid to S. aureus, P. aeruginosa CNS and E. Faecalis.

Bacteria↗
PubMed1993

Multiple mediators and mechanisms are involved in the adaptive cytoprotection provided by certain mild irritants.

We investigated the participation of prostaglandins (PG) and nitric oxide (NO) in adaptive cytoprotection using 0.6 N HCl-induced gastric lesions in the rat stomach. Indomethacin reversed the protective effect of 0.2 N HCl more strongly than that of 0.35 N HCl, both of which markedly inhibited HCl ulcer. NG-Nitro-L-arginine (L-NNA) did not affect the protective effect afforded by either 0.2 N HCl or 0.35 N HCl. Combined pretreatment with indomethacin and L-NNA did not diminish the protective action induced by 0.35 N HCl, but almost completely abolished the indomethacin-resistant protection afforded by 0.1 N NaOH. Acid mild irritant increased the gastric fluid volume concentration-dependently, whereas alkaline mild irritant had little or no effect on the volume. These results suggest that: 1) The mediators involved in adaptive cytoprotection afforded by 0.1 N NaOH may be fully ascribed to PG and NO; 2) PG is a major mediator in the protection induced by 0.2 N HCl; 3) In the case of 0.35 N HCl, the mediators remain to be determined since increased gastric fluid volume could contribute to the protection through dilution. These findings thus may indicate that multiple mediators and mechanisms are implicated in adaptive cytoprotection.

Animals↗