Search PubMed⌕ Search

Biomedical subjects

H Araki

Publications and source records attributed to H Araki.

At least 163 records · Page 9Linked to original sources

[Combined chemotherapy with 5-FU and low dose CDDP for advanced or recurrent cancer of the digestive system and home anti-cancer chemotherapy].

We have performed combined chemotherapy with 5-FU, a biochemical modulator, and low dose CDDP for advanced or recurrent cancer of the digestive system. The therapy was effective in 37% of all cases and in 45.5% and 41.6% of esophageal and gastric cancer cases, respectively. In addition, few patients developed adverse side effects including renal disorders, one of the major side effects of CDDP. Therefore, we considered home anti-cancer chemotherapy feasible. For 27 outpatients with advanced cancer of the digestive system including 15 cases of esophageal cancer, 4 cases of gastric cancer, 3 cases of colon cancer, 4 cases of pancreatic cancer and 1 case of gall bladder cancer, 4 to 6 week home adjuvant chemotherapy was performed. The regimen comprised 1 week of oral administration of 300 mg/body/day of UFT-E granules and 5 days of continuous intravenous infusion of 25 mg/body/day of CDDP using an infusor pump. During the follow-up, 3 cases of catheter obstruction, 3 cases of catheter sepsis and 1 case of pneumothorax appeared. These complications all resulted from the catheter, and safe home anti-cancer chemotherapy could be continued because 5-FU and CDDP did not cause severe side effects.

Administration, Oral↗

Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe.

We cloned by phenotypic complementation a novel Saccharomyces cerevisiae's multicopy suppressor of the Schizosaccharomyces pombe cdc10-129 mutant which we call HAC1, an acronym of 'homologous to ATF/CREB 1'. It encodes a bZIP (basic-leucine zipper) protein of 230 amino acids with close homology to the mammalian ATF/CREB transcription factor and gel-retardation assays showed that it binds specifically to the CRE motif. HAC1 is not essential for viability. However, the hac1 disruptant becomes caffeine sensitive, which is suppressed by multicopy expression of the yeast PDE2 (Phosphodiesterase 2) gene. Although the mRNA level of HAC1 is almost constitutive throughout the cell cycle, it fluctuates during meiosis. The upstream region of the HAC1 gene contains a T4C site, a URS (upstream repression sequence) and a TR (T-rich) box-like sequence, which reside upstream of many meiotic genes. These results suggest that HAC1 may also be one of the meiotic genes.

3',5'-Cyclic-AMP Phosphodiesterases↗

A new variant Cu/Zn superoxide dismutase (Val7-->Glu) deduced from lymphocyte mRNA sequences from Japanese patients with familial amyotrophic lateral sclerosis.

We have identified a new mutant Cu/Zn superoxide dismutase (SOD1) deduced from the nucleotide sequences of peripheral blood lymphocyte mRNA from Japanese patients with familial amyotrophic lateral sclerosis (FALS). Sequence analysis of reverse transcriptase-initiated PCR amplified mRNA revealed a heterozygosity indicative of one normal allele and one variant allele with a T-->A transversion. This base change led to replacement of valine by glutamic acid at position 7 of 153-residue SOD1 molecule, and produced a new restriction site for Alu I in the exon 1. Restriction fragment length polymorphism analysis confirmed the linkage of this mutation with this type of FALS. Both enzymatic activity and protein of the SOD1 were reduced in red blood cells from the patient.

Adult↗

Effect of NE-100, a novel sigma receptor ligand, on phencyclidine-induced cognitive dysfunction.

N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) is a selective and potent sigma receptor ligand. We investigated the effects of NE-100 on phencyclidine (PCP)-induced cognitive dysfunction in rats in a water maze task. NE-100 significantly shortened the PCP-induced prolonged swimming latency as did 1-(cyclopropylmethyl)-4-[2'(4"-fluorophenyl)-2'-oxoethyl]- piperidine monohydrobromide (Dup 734), 4-[2'-(4"-cyanophenyl)-2'-oxoethyl]-1-(cyclopropyl-methyl)pi peridine (XJ 448), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY 14802) and rimcazole, all of which are sigma receptor ligands and possibly antagonists. Ritanserin, a 5-HT2 receptor antagonist, also showed a tendency to shorten swimming latencies. Latencies of haloperidol-, cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-2-methoxy-5-chloro-4-met hyl- aminobenzamide (YM-09151-2)- and sulpiride-, dopamine D2 receptor antagonists, treated groups did not differ from that seen in the PCP-treated group. Thus, PCP-induced cognitive dysfunction may be improved by sigma receptor ligands.

Animals↗

The RFC2 gene encoding a subunit of replication factor C of Saccharomyces cerevisiae.

Replication Factor C (RF-C) of Saccharomyces cerevisiae is a complex that consists of several different polypeptides ranging from 120- to 37 kDa (Yoder and Burgers, 1991; Fien and Stillman, 1992), similar to human RF-C. We have isolated a gene, RFC2, that appears to be a component of the yeast RF-C. The RFC2 gene is located on chromosome X of S. cerevisiae and is essential for cell growth. Disruption of the RFC2 gene led to a dumbbell-shaped terminal morphology, common to mutants having a defect in chromosomal DNA replication. The steady-state levels of RFC2 mRNA fluctuated less during the cell cycle than other genes involved in DNA replication. Nucleotide sequence of the gene revealed an open reading frame corresponding to a polypeptide with a calculated Mr of 39,716 and a high degree of amino acid sequence homology to the 37-kDa subunit of human RF-C. Polyclonal antibodies against bacterially expressed Rfc2 protein specifically reduced RF-C activity in the RF-C-dependent reaction catalyzed by yeast DNA polymerase III. Furthermore, the Rfc2 protein was copurified with RF-C activity throughout RF-C purification. These results strongly suggest that the RFC2 gene product is a component of yeast RF-C. The bacterially expressed Rfc2 protein preferentially bound to primed single-strand DNA and weakly to ATP.

Amino Acid Sequence↗

The survival of rat cerebral cortical neurons in the presence of trophic APP peptides.

One function of Alzheimer amyloid protein precursor (APP) is the regulation of growth and differentiation in several types of cells, including fibroblasts, PC12 cells, and neurons. This activity is represented by a small stretch of amino acids in the center of the molecule around RERMS. The APP 17-mer peptide containing the RERMS domain supported survival and neurite extension of rat cortical neurons in a dose-dependent and sequence-specific manner. The APP fragment synthesized in Escherichia coli supported the survival and neurite extension of rat cortical neurons, whereas the mutant APP fragment lacking the 30 amino acids around the RERMS domain had drastically reduced activity to support the survival and neurite extension. The current study established APP as a neuron survival factor and determined that the sequence around RERMS is important for this function.

Alzheimer Disease↗

Threshold of the soleus muscle H-reflex is less sensitive to the change in excitability of the motoneuron pool during plantarflexion or dorsiflexion in humans.

In the present study, we investigated whether weak (10% of maximal voluntary contraction) tonic dorsiflexion (DF) and plantarflexion (PF) affects the two conventional parameters used for evaluating the excitability of the soleus motoneuron (MN) pool, i.e. the ratio of the threshold of H-reflex to that of M-response (Hth:Mth) and the ratio of the maximal amplitude of H-reflex to that of M-response (Hmax:Mmax) in human subjects. The results showed that the Hmax:Mmax decreased during DF and increased during PF compared with that during rest, whereas no clear alteration was observed in Hth:Mth. These results are consistent with the scheme proposed by earlier workers, who have argued that neither inhibitory nor facilitatory effects of the conditioning stimulus apply to specific spinal reflex circuits occurring around the threshold of the test H-reflex. It is suggested, therefore, that the conventional use of the Hth:Mth ratio as a parameter reflecting the excitability of the MN pool should be reconsidered.

Adult↗

Effects of an apovincaminic acid derivative VA-045 on neuronal activity in rat brain stem reticular formation.

Extracellular single unit and spontaneous cortical electroencephalographic (ECoG) recordings were made in the brain stem reticular formation (RF) and the frontal cortex, respectively, of urethane-anesthetized rats. VA-045, an apovincaminic acid derivative had no significant effects on the spontaneous firing rate of the RF neurons and ECoG. Closed head injury (CHI) was induced by dropping a 400 g weight through a tube from 70 cm on a steel helmet placed on the vertex. CHI led to a reduction in the firing rate of RF neurons and ECoG synchronization. VA-045 dose-dependently reversed the CHI-induced decrease in the firing rate of RF and led to ECoG desyncronization. Clonidine, an alpha 2 adrenoceptor agonist, and scopolamine, a muscarinic receptor antagonist, also reduced the firing rate of RF neurons and led to ECoG synchronization. VA-045 dose-dependently antagonized the effects of clonidine, but not the effects of scopolamine on RF neuronal activity and ECoG. Thus, VA-045 has an ameliorating effect on the CHI-induced depression of neuronal activity in the RF. A central alpha 2 adrenoceptor antagonistic action may be involved.

Animals↗

A rat model of phencyclidine psychosis.

Phencyclidine (PCP)-induced behavior in rats was investigated in water maze and diving behavior tasks. The swimming and diving latencies of PCP-treated groups placed in a water maze apparatus were gradually shortened, and prolonged, respectively, while rats in a control group performed well. In all rats, stereotyped behavior and hyperlocomotion were absent. We propose that this animal model induced by lower doses of PCP may be useful for further studies to research schizophrenia.

Analysis of Variance↗

NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats, dogs and monkeys.

Phencyclidine (PCP)-induced psychosis is a useful animal model for studies on schizophrenia. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]- ethylamine monohydrochloride (NE-100) had no effect on conditioned avoidance responses (CAR) in rats, whereas, the PCP-induced impairment of avoidance inhibition was attenuated by NE-100. The PCP-induced ataxia or decreased attention in rhesus monkeys was to some extent overcome by NE-100. In dogs, PCP-induced either head-weaving behavior or ataxia, effects which were blocked by NE-100. Administration of PCP led to an increase in beta-2 and a decrease in delta relative power (RP) activity in cortical background spectral electroencephalographics (ECoG) in dogs. While NE-100 in itself showed no significant change in beta-2 and delta RP, NE-100 did block the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effect of PCP in experimental animals. This drug is being considered as a therapeutic for the treatment of patients in the schizophrenia.

Animals↗

Effects of VA-045, a novel apovincaminic acid derivative, on age-related impairment evidence in electroencephalograph, caudate spindle, a passive avoidance task and cerebral blood flow in rats.

1. The ability of VA-045 to improve aged-related impairment on electroencephalograph (EEG), caudate spindle, performance on a passive avoidance task and cerebral blood flow (CBF) were evaluated in rats. 2. The cortical EEG of the aged rats showed a higher incidence of spontaneous spindle burst (SSB) than seen in young rats. VA-045 decreased the incidence of SSB in aged rats. In contrast, vinpocetine increased the incidence of SSB in aged rats. 3. Electrical stimulation of the striatum in aged rats lead to a higher incidence of neocortical high voltage spindle (CS) than seen in young rats. In young rats, VA-045 had no effect on the CS, whereas an age-related increase in CS was blocked by VA-045, but was enhanced by vinpocetine. 4. There were no differences in the cortical EEG arousal response elicited by stimulation of the reticular formation of the brain stem in rats of all ages. VA-045 and vinpocetine had no effect on the cortical EEG arousal response in both young and aged rats. 5. VA-045, but not vinpocetine, attenuated the age-related decreased step through latency (STL) on a passive avoidance task. VA-045 and vinpocetine did not enhance the acquisition of learning behavior in a passive avoidance task in young rats. 6. VA-045 increased the cerebral blood flow (CBF) in both young and aged rats and the potency in aged rats was greater than that in young rats. Vinpocetine had no effect on CBF in either young or aged rats. 7. The pharmacological effects of VA-045 on age-related neuronal dysfunction are discussed.

Aging↗

Changes in the extracellular concentrations of amino acids in the rat striatum during transient focal cerebral ischemia.

Although considerable evidence supports a role for amino acids in transient global cerebral ischemia and permanent focal cerebral ischemia, effects of transient focal cerebral ischemia on the extracellular concentrations of amino acids have not been reported. Accordingly, our study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, GABA, taurine, glutamine, alanine, and phosphoethanolamine in the striatum of transient focal cerebral ischemia, as evidence to support their pathogenic roles. Focal ischemia was induced using the middle cerebral artery occlusion model, with no need for craniotomy. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. One hour of middle cerebral artery occlusion followed by recirculation caused neuronal damage that was common in the frontoparietal cortex and the lateral segment of the caudate nucleus. During 1 h of ischemia, the largest increase occurred for GABA and moderate increases were observed for taurine, glutamate, and aspartate. Alanine, which is a nonneuroactive amino acid, increased little. After recirculation, the levels of glutamate and aspartate reverted to normal baseline values right after reperfusion. Despite these rapid normalizations, neuronal damage occurred. Therefore, uptake of excitatory amino acids can still be restored after 1 h of middle cerebral artery occlusion, and tissue damage occurs even though high extracellular levels of glutamate are not maintained.

Amino Acids↗

Local cerebral blood flow and glucose metabolism in chronic focal ischaemia of stroke-prone spontaneously hypertensive rats.

The relationship between local cerebral blood flow (ICBF) and local cerebral glucose metabolism (ICGU) at the chronic stage of focal cerebral ischaemia was assessed in young stroke-prone spontaneously hypertensive rats (SHRSP) following occlusion of the distal middle cerebral artery (MCA). On day 7 following this occlusion, ICBF and ICGU were measured by autoradiographic methods using 14C-iodoantipyrine and 14C-2-deoxyglucose (2DG), respectively. The infarct was limited to the ipsilateral cerebral cortex. A narrow band of increased uptake of 14C-2DG was observed in the border zone at the periphery of infarcted areas. The ICBF in the ischaemic cortex revealed a graded reduction from the ischaemic centre to the surrounding tissues. A significant reduction in ICGU coupled to CBF was also observed in 4 of 13 selected noninfarcted regions ipsilateral to the MCA occlusion. The ischaemic regions had a significant increase in water content. The region with ischaemic oedema was limited to a narrow area compared with the findings regarding ICBF and ICGU. The SHRSP strain has more severe cerebral ischaemia, oedema formation, and metabolic derangement at the chronic stage of focal ischaemia, compared to normo-tensive animals.

Animals↗

A case of siblings with Meckel's diverticulum diagnosed before operation.

The authors encountered a sibling case of Meckel's diverticulum in 9 and 11 year old Japanese boys. They were diagnosed using contrast examination and 99mTc-pertechnetate scintigraphy before operation. The familial tendency is one in every 2500 families. Only 15 cases of familial occurrence have been reported by five authors.

Anastomosis, Surgical↗

[False positives and false negatives seen in anti-HIV-1 antibody tests].

From September 1986 to December 1993 31059 anti-HIV antibody tests were performed on the samples from our clinic, from 29 health centers and their branches of Osaka Prefecture, from a hospital and from high risk groups. Enzyme immune assay (EIA) was used up to 1988 and from 1989 particle agglutination (PA) has been employed. The indeterminates of Western blot (WB) were seen in 5 EIA positives and in 2 PA positives. False positive rate of EIA was 0.235% (11/467) and that of PA was 0.011% (2/17922). Two false negative cases of anti-HIV-1 antibody test due to window period were documented and the importance of co-use of antigen test at the time of confirmative antibody tests was discussed.

Agglutination Tests↗

Changes in locomotor activity and passive avoidance task performance induced by cerebral ischemia in Mongolian gerbils.

BACKGROUND AND PURPOSE: We investigated changes in locomotor activity, passive avoidance task performance, and hippocampal CA1 neurons induced by cerebral ischemia in Mongolian gerbils to examine the relation between these behavioral changes and CA1 neuronal damage. METHODS: Spontaneous locomotor activity was measured using the open field method before and 1, 3, 7, 14, or 28 days after 1- to 5-minute occlusion of the bilateral common carotid arteries. Locomotor activity after the second episode of 5-minute ischemia was also measured at 1-month intervals. The passive avoidance task was performed 7 or 28 days after induced ischemia. Histopathological changes in CA1 neurons after ischemia were assessed. RESULTS: Locomotor activity was increased 1 and 3 days after induced ischemia but not 14 and 28 days later. When the gerbils were again subjected to 5-minute ischemia 1 month after the initial 5-minute induced ischemia, locomotor activity even 1 day later was significantly increased. In contrast, passive avoidance impairment depended on the duration of ischemia, as determined 7 and 28 days after induced ischemia. Hippocampal CA1 neuronal damage was progressive, that is, changes in CA1 neurons were apparent even 1 day after 5 minutes of induced ischemia, and the CA1 neurons disappeared 7 days after 5 minutes of ischemia. CONCLUSIONS: Passive avoidance impairment after ischemia is related to damage of CA1 neurons. Changes in locomotor activity after induced ischemia do not seem to be linked to CA1 neuronal damage.

Animals↗

Increased heart rate and blood pressure response, and occurrence of arrhythmias in elderly swimmers.

Changes in the heart rate (HR) and blood pressure, and the occurrence of arrhythmias after swimming were examined in 52 members of swimming classes aged 40 to 76 years. After swimming 25 m twice at a usual intensity, HR increased markedly in the subjects to 87 +/- 11% of predicted maximal HR, while the rate of perceived exertion was modest. The systolic blood pressure (SBP) also increased significantly, and SBP of 200 mmHg or higher was exclusively observed in subjects 60 years or older. After entering the pool, immersing the face and swimming, 28 subjects (54%) developed various arrhythmias. Premature ventricular contraction (PVC) was provoked or aggravated by swimming in 19 subjects. The incidence of PVC provocation or aggravation increased as SBP at rest or age increased. Swimming causes marked rise in HR and SBP in elderly subjects, and frequently provokes or aggravates PVC in older subjects and/or in subjects with higher SBP at rest.

Adult↗

Structure-activity relationships of unsaturated long chain fatty acids in relation to the inhibition of gastric H+,K(+)-ATPase.

Structure-activity analyses of the effects of unsaturated fatty acids on the inhibition of gastric H+,K(+)-ATPase were carried out. Saturated fatty acids are poor inhibitors of H+,K(+)-ATPase, compared with unsaturated ones. Among the cis-unsaturated fatty acids with one double bond, there was an optimal carbon chain length for the inhibitory of the enzyme, and 10-nonadecenoic acid (C19:1) was the most potent inhibitor. The inhibitory activity was not altered by a change in the position of the double bond. The cis-fatty acids were more potent than the corresponding trans-fatty acids. Esterification of the acid moiety resulted in a decrease of the inhibitory activity. However, conversion of the acid moiety into alcohol and amide did not decrease the activity. These findings suggest that two moieties of unsaturated fatty acids are important in the interaction with the gastric H+,K(+)-ATPase, the carbon chain, which may have some hydrophobic interactions with the enzyme, and the terminal functional group (acid moiety), which may interact with hydrophilic interactions such as through hydrogen bonds with the enzyme.

Animals↗