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Biomedical subjects

K Adachi

Publications and source records attributed to K Adachi.

At least 379 records · Page 21Linked to original sources
PubMed1992

Enhancement of epidermal growth factor receptor expression on glioma cells by recombinant tumor necrosis factor alpha.

Recombinant tumor necrosis factor alpha (rTNF alpha; optimal dose 1000 U/ml) significantly increased the density of epidermal growth factor receptor (EGF-R) in three of four glioma cell lines in culture as determined by binding analysis of anti-EGF-R monoclonal antibody (mAb) 425. Since enhancement of EGF-R expression by rTNF-alpha was inhibited when cells were treated with the protein synthesis inhibitor cycloheximide, the effects of rTNF alpha may be protein-synthesis-dependent. The dose of rTNF alpha that was optimal for up-regulation of EGF-R on glioma cells did not inhibit the growth of these cells. 125I-labeled mAb 425 lysed glioma cells in culture following its internalization into the cells. After glioma cells had been treated with rTNF alpha, the growth-inhibitory effects of the mAb were significantly enhanced, probably a reflection of the increase in EGF-R density on the tumor cell surfaces. The rTNF alpha effects were specific to the EGF-R and did not affect unrelated glioma-associated antigens. In our previous clinical trials, 125I-labeled mAb 425 showed immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with 125I-labeled mAb 425 and rTNF alpha.

Antibodies, Monoclonal↗
PubMed1992

Location of neutralizing epitopes on the hemagglutinin-esterase protein of influenza C virus.

Neutralization-resistant variants of influenza C/Ann Arbor/1/50 virus were selected with monoclonal antibodies against four different antigenic sites on the hemagglutinin-esterase (HE) glycoprotein, and their HE genes were sequenced to identify amino acid residues important for the integrity of each site. Twelve different amino acid substitutions in a total of 18 antigenic variants were all located on the HE1 subunit. Although variants for antigenic site A-2 had a change at position 367, all substitutions in the variants for sites A-1, A-3, and A-4 occurred in the central region of the HE1 spanning amino acid positions 178 to 283. Furthermore, it was found that many of the substitutions in the variants selected with antibodies to sites A-1 and A-3 were clustered within or near one of the three variable regions revealed previously by comparing amino acid sequences of the HEs among various influenza C isolates (Buonagurio, D. A., Nakada, S., Fitch, W. M., and Palese, P., Virology 146, 221-232, 1985). The antigenic variants were also examined for their ability to agglutinate chicken and human erythrocytes in order to obtain information concerning the receptor-binding site on the HE molecule. The results suggested that the amino acid changes at residues 178, 186, 187, 190, 206, 212, and 226 decreased the hemagglutinating activity whereas those at residues 245, 266, and 283 produced an opposite effect.

Amino Acid Sequence↗
PubMed1992

Alteration in the immunoreactivity of the calcineurin subunits after ischemic hippocampal damage.

Dephosphorylation processes of target proteins are critical to the reversible regulation of intracellular signal transduction systems. Further, brain damage such as ischemic insult induces marked changes in protein kinase activity. To study these changes more thoroughly, specific monoclonal antibodies of the A and B subunits of calcineurin (protein phosphatase 2B) were raised, and regional alterations in the immunoreactivity of calcineurin in the rat hippocampus were investigated after a transient forebrain ischemic insult causing selective and delayed hippocampal CA1 pyramidal cell damage. In normal rats it was found that both the calcineurin A and the B subunits showed high immunoreactivity in the dendritic fields of the hippocampal formation. The immunoreactivity of subunit A in the strata oriens, the radiatum of the CA1 subfield and in the stratum lucidum of the CA3 subfield was most intense, whereas the immunoreactivity in the other CA3 subfields and in the dentate gyrus was relatively low. In contrast, the dendritic fields of the hippocampal formation were equally immunoreactive to calcineurin subunit B, although the stratum lucidum of the CA3, where the mossy fibers from the dentate granule cells terminate, showed a very high immunoreactivity of the B subunit. After transient forebrain ischemia in the CA1 subfield, where selective pyramidal cell death occurred two days after this ischemia, a marked loss of immunoreactivity in both subunits was observed, along with morphological pyramidal cell damage. A recovery of the immunoreactivity of A and B subunits in the strata oriens and radiatum was later noted 30 days after ischemia. In the stratum lucidum of the CA3, the immunoreactivity of both the A and B subunits was transiently depressed from 6 to 24 h, followed by a marked immunoreactivity enhancement from four to 30 days after ischemia. Further, in the histologically intact dentate gyrus, both the immunoreactivity of the A and B subunits in the molecular layer were transiently enhanced from four to 14 days after ischemia, particularly in the supragranular layer. The results clearly indicate that the protein dephosphorylation systems were markedly altered in the whole hippocampal formation during the recirculation period following ischemia. Further, the transient depression in the calcineurin immunoreactivity seen in the mossy fiber terminals may reflect modulated synaptic activity of the dentate granule cells, which may play a pivotal role in the delayed and selective death of the CA1 pyramidal cells. Thus, calcineurin appears to be an excellent marker enzyme for the detection of neuronal activity and synaptic plasticity after brain damage, such as an ischemic insult.

Animals↗
PubMed1992

Antigenic and genetic analyses of eight influenza C strains isolated in various areas of Japan during 1985-9.

Eight strains of influenza C virus isolated in various areas of Japan between January 1985 and January 1989 were compared using monoclonal antibodies to the haemagglutinin-esterase (HE) glycoproteins and by oligonucleotide mapping of total vRNA. Five of six strains isolated during 1986-9 were closely related to one another and also resembled the virus, C/Aichi/1/81, isolated in 1981 in Aichi prefecture. This suggests that the C/Aichi/1/81-related viruses had an epidemiological advantage over any co-circulating viruses at least during that period. One of two 1985 isolates (C/Nara/1/85) was antigenically indistinguishable from the C/Mississippi/1/80 strain though their oligonucleotide patterns were markedly different from each other. This raises the possibility that C/Nara/1/85 may be a recombinant virus which receives its HE gene from the C/Mississippi/1/80-related parent.

Antigens, Viral↗
PubMed1992

Evaluation of the in vitro antiproliferative properties of four novel anthracyclines YM1, 3, 4 and 6 in human leukemia cell lines.

The antitumor activity of novel doxorubicin analogues YM1, YM3, YM4 and YM6 was evaluated against drug sensitive U937 monocytic leukemia and CCRF-CEM lymphoid leukemia cell lines, as well as drug resistant CEM/VLB100 lymphoid multidrug resistant leukemia cell line by a [3H]thymidine incorporation assay. Different antileukemic activities of these new anthracyclines were observed in our studies. These novel anthracyclines produced a dose- and time-dependent inhibition in all the leukemic cell lines tested, while YM1 and YM3 were more effective than YM4 and YM6 against all the leukemic cell lines. The antitumor activity of all these novel analogues was lower than that of doxorubicin or epidoxorubicin in drug sensitive leukemic cells. The relative resistance values (IC50 of resistant cell line/IC50 of sensitive parental cell line) of YM1, 3, 4 and 6 were 27, 7, 5 and 14 respectively. These were lower than the resistance values for ADM and EDR which were 45 and 40 respectively. YM3 had a similar antileukemic activity against the CEM/VLB100 drug resistant leukemic cell line to ADM or EDR with a lower relative resistance value and a slightly increased IC50 value. Our results suggest that YM3 may be used in high dose for the clinical treatment of leukemias with possible less cardiotoxicity as well as less drug resistance.

Antineoplastic Agents↗
PubMed1992

Oxygen binding and other physical properties of human hemoglobin made in yeast.

Wagenbach et al. (1991, BioTechnology, 9, 57-61) have recently developed a system for producing soluble recombinant tetrameric hemoglobin in yeast: hemoglobin begins to appear 4-5 h after induction with galactose, alpha- and beta-globin chains fold in vivo and endogeneously produced heme is incorporated into hemoglobin tetramers. We have further characterized the oxygen-binding properties, as well as the tetramer stability, of recombinant human Hb A made in yeast. After purification by ion-exchange chromatography, a single band at the same position as normal human Hb A was obtained using cellulose acetate electrophoresis. Although the oxy and deoxy forms of purified recombinant Hb A made in yeast were spectrophotometrically identical to native human Hb A, the oxygen-binding curve was shifted slightly left of that for native human Hb A. Further purification of recombinant hemoglobin by FPLC revealed two fractions: one (fraction B) with low cooperativity and high oxygen affinity, and the other (fraction A) with almost identical cooperativity and oxygen affinity compared with native human Hb A. The Bohr effect of fraction A was also identical to native human Hb A. Hemoglobin in fraction B with lowered cooperativity precipitated approximately 1.5 times faster than normal human Hb A during mechanical agitation, while hemoglobin in fraction A with normal cooperativity precipitated with kinetics identical to native human Hb A. These results suggest that some of the recombinant molecules made in yeast fold improperly, and that these molecules may exhibit decreased cooperativity for oxygen binding and decreased stability.(ABSTRACT TRUNCATED AT 250 WORDS)

Allosteric Regulation↗
PubMed1992

Effects of alkyl alcohols and related chemicals on rat liver structure and function. III. Physiochemical properties of ethanol-, propanol- and butanol- treated rat liver mitochondrial membranes.

The physicochemical properties of mitochondria in liver tissue obtained from rats given 32% ethanol, 32% propanol or 6.9% butanol in drinking water for up to 3 months were investigated using differential scanning calorimetry and fluorescence polarization measurements. The results obtained were as follows: 1) Phospholipids extracted from mitochondria showed increases in the relative amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylserine, and a decrease in the relative amount of phosphatidylethanolamine. An increase in the unsaturated/saturated fatty acid ratio of phospholipids was also observed. 2) Elevation of the thermotropic lipid phase transition temperature with a decrease in the enthalpy value (delta H) was revealed by differential scanning calorimetry. 3) The elevation of the lipid phase transition temperature was detected also by fluorescence polarization measurements using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe. Elevation of mitochondrial membrane fluidity was found in some of the experimental animals, but most showed no changes in comparison with the control. A possible role of membrane fusion in the mechanism of formation of ethanol-, propanol- and butanol-induced hepatic megamitochondria is discussed on the basis of these results.

1-Propanol↗
PubMed1992

Negative regulation of catalase gene expression in hepatoma cells.

For an understanding of the molecular basis of the marked decrease in catalase activity of various tumor cells, expression of the catalase gene was studied in rat and human hepatoma cell lines and in rat liver, which was used as a control with high activity. RNA blot hybridization profiles and run-on assays indicated that the decrease in catalase activity was due to depression of catalase gene transcription. Chloramphenicol acetyltransferase (CAT) assays for the fragments with various lengths of the 5'-flanking region (up to -4.5 kb from the ATG codon) of the catalase gene revealed the presence of several cis-acting elements involved in the negative regulation of transcription. The most-upstream element with the strongest activity (-3504 to -3364 bp), when linked to the catalase promoter region (-126 bp) of the CAT construct and subjected to an in vitro transcription assay, did not yield transcripts in experiments with the hepatoma nuclear extract, whereas the unlinked template did yield transcripts. A gel shift competition assay using hepatoma nuclear extract showed the core sequence of the silencer element to be 5'-TGGGGGGAG-3'. A homology search found that the same core sequence was also present in 5'-flanking regions of the albumin gene and of some other liver enzyme genes, the expression of which has been reported to be down regulated in some hepatoma cells. Southwestern (DNA-protein) analysis demonstrated that an approximately 35-kDa nuclear protein bound to the silencer element was present in hepatoma cells but not in rat liver cells.

Animals↗
PubMed1992

Magnesium and calcium contents in CNS tissues of amyotrophic lateral sclerosis patients from the Kii peninsula, Japan.

To further elucidate the involvement of metals as a factor in the pathogenesis of amyotrophic lateral sclerosis (ALS) on the Kii peninsula of Japan, a well-known high incidence area of ALS with low calcium and magnesium contents in soil and drinking water, we determined concentrations of these metals in samples of central nervous system tissue taken from postmortem ALS cases. Calcium content was determined by neutron activation analysis and magnesium by inductively coupled argon plasma emission spectrometry. From 5 ALS cases and 5 neurologically normal controls, we examined tissues from the precentral gyrus, including the motor cortex, internal capsule, crus cerebri and spinal cord, and from 22 other areas. The average calcium content in precentral gyrus, internal capsule, crus cerebri and spinal cord in ALS cases was higher than that in the controls, and the mean value of all 26 areas in the ALS cases was also higher than that of the controls. The average magnesium content of each region as well as the mean value of the 26 regions in the ALS cases was significantly lower than that in the controls. The Ca/Mg ratio of the 26 ALS regions was significantly higher than that of controls. This study strengthens our hypothesis that an abnormal metal metabolism plays a responsible role in the Ca-hydroxyapatite formation observed in central nervous system tissue of ALS cases, leading to motor neuron death and degeneration of the pyramidal tracts.

Adult↗
PubMed1992

Effect of serotonin on the immunoreactive thyrotropin-releasing hormone concentrations of the rat stomach.

The effects of serotonin and its related compounds on immunoreactive thyrotropin-releasing hormone (ir-TRH) concentrations of the rat stomach wall and gastric juice were studied. Either serotonin, cyproheptadine or GR38032F was injected intraperitoneally, and the rats were decapitated at various times after the injection. ir-TRH concentrations of the stomach wall and gastric juice were measured by radioimmunoassay, and gastric serotonin concentrations were measured by HPLC. ir-TRH concentrations of the stomach wall decreased, and ir-TRH concentrations of gastric juice increased significantly after serotonin injection. On the other hand, both cyproheptadine and GR38032F did not affect ir-TRH concentrations of the stomach. The effects of serotonin on ir-TRH concentrations of the stomach were significantly blocked by the pretreatment of cyproheptadine and GR38032F. The reciprocal changes of gastric ir-TRH and serotonin concentrations were observed without changes in gastric juice pH. These findings suggest that serotonin stimulates ir-TRH release from the stomach wall into gastric juice, and the effects of serotonin on ir-TRH release may be partly mediated via 5-HT2- and 5-HT3-receptors.

Animals↗
PubMed1992

Induction of junB expression, but not c-jun, by granulocyte colony-stimulating factor or macrophage colony-stimulating factor in the proliferative response of human myeloid leukemia cells.

The proliferative effects of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) on human hematopoietic cells have been reported, but the intranuclear mechanism of early signal response to these mitogenic stimuli remains unknown. Using an established human myeloid leukemia cell line (NKM-1) which can grow in serum-free medium in response to G-CSF or M-CSF, we examined expressions of the jun family genes, c-jun, junB, and junD, which are coexpressed by various growth factors in many tissues. In parallel with regrowth from the G0/G1 resting state by addition of recombinant human G-CSF or M-CSF after serum deprivation, NKM-1 cells showed the transient expression of the junB gene with a peak of ninefold above the basal level between 40 and 60 min. In contrast, c-jun expression was not stimulated by these CSFs. JunD expression was constitutively observed at detectable levels. Furthermore, c-fos mRNA was rapidly induced to a peak of 14-fold after CSF stimulation. Transcriptional run-on assays revealed that treatment of serum-starved NKM-1 with 50 ng/ml G-CSF or M-CSF increased the transcription rate of the junB gene and the c-fos gene by 1.8-fold and 2.9-fold, respectively, but did not induce any transcript of the c-jun gene. The results indicate that the expression of the junB and c-fos genes is activated, at least in part, at the transcriptional level in response to these CSFs. These findings suggest that the signal activating c-jun expression might not be involved in the proliferative action of G-CSF and M-CSF but junB may be one of important elements in early response events of the signal transduction system in human CSF-responsive hematopoietic cells.

Cell Division↗
PubMed1992

Anti-erythrocyte membrane antibodies detected in sera of dogs naturally infected with Babesia gibsoni.

Due to the potential for anti-erythrocyte membrane antibodies as possible enhancers of erythrocyte destruction, the presence of serum anti-erythrocyte membrane antibodies in 31 dogs with Babesia gibsoni infection admitted to a veterinary hospital was investigated by an enzyme linked immunosorbent assay (ELISA) and immunoblotting analyses. This infection resulted in an increase of anti-erythrocyte membrane antibodies in 84% (IgG) and 74% (IgM) of 31 infected dogs, respectively. This was confirmed by the similarity in the protein profiles of the erythrocyte membrane antigens immunoblotted with rabbit antiserum to dog erythrocyte membrane antigens and infected dog serum. These results suggest the production of anti-erythrocyte membrane antibodies was induced by B. gibsoni infection.

Anemia↗
PubMed1992

Changes in anti-erythrocyte membrane antibody level of dogs experimentally infected with Babesia gibsoni.

To account for the conflict between the excessive destruction of erythrocytes and the number of parasitized erythrocytes in dogs infected with Babesia gibsoni, we examined the correlation between anti-erythrocyte membrane antibody level (AEMAL) and the number of erythrocytes (RBC count) in dogs with experimentally induced babesiosis using hematological examination and an enzyme linked immunosorbent assay (ELISA). In the infected dogs without splenectomy, more prominent reduction in RBC count accompanied with the elevated AEMAL was presented than anticipated from parasitemia until the 21st day. Furthermore, autoagglutinated erythrocytes and spherocytes were demonstrated in blood films. These results suggest that a humoral immunologic mechanism may be involved in a decrease in RBC count in dogs infected with B. gibsoni.

Anemia↗
PubMed1992

[Retrieval of faces from features described by eyewitnesses].

UNLABELLED: This experiment proposes a computer technique to find a witnessed one in the database of faces, from an eyewitness's feature description. The method is basically to choose the face with maximum likelihood for an eyewitness's description. The likelihood is derived from one of three models, in which the description of a features by a witness is based on either (i) judgement through all features, (ii) feature sampling with replacement, or (iii) feature sampling without replacement. Three models were assessed by free description task of facial features. RESULTS: these three models showed sufficient accuracy of retrieval, and the feature sampling without replacement model was superior to other two models.

Adult↗
PubMed1992

[Spastic paraparesis and sensory disturbance improved by prednisolone therapy].

We reported a 65-year-old man whose sister was suffering from HTLV-I-associated myelopathy (HAM) and who presented slowly progressive spastic paraparesis, sensory disturbance in the feet, tremors and cerebellar ataxia. He was also positive for serum anti-HTLV-I antibody. He first showed a head tremor at the age of 3 years. He developed a spastic and ataxic gait when aged 15 years, and it became difficult for him to walk at the age of 50 years. Examination at 65 years showed a spastic and ataxic gait and scanning speech. Hyper-reflexia and Bahinski's signs were observed. Sensation in the feet was decreased. The anti-HTLV-I antibody titer in the serum was 1:512 by the PA method, and Western blot analysis revealed bands of P19, P24, P28 and P32. Examination of the cerebrospinal fluid (CSF), including oligoclonal bands, gave normal results. The CSF was negative for anti-HTLV-I antibody. CT and MRI of the head showed cerebellar atrophy. His sister was 60 years old. She had developed a spastic gait at the age of 15 years. Sensory defects and bladder dysfunction developed when aged 35 years. Hyper-reflexia, Babinski's sign and foot clonus were observed. Sensation in the feet was decreased. The urinary residual volume was increased. Ataxia was not observed. The anti-HTLV-I antibody titer in the serum was 1:8,192 by the PA method, and Western blot analysis revealed bands of p24, p28 and p32. Examination of the CSF, including oligoclonal bands, gave only normal results.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Chlamydia trachomatis infection with symptoms and signs of the central nervous system damage--a case report].

A 32-year-old woman developed myalgia, fever, consciousness disturbance, mental disorder, pyramidal tract signs and meningeal irritation signs at about 2 months after a normal labor. Laboratory examination showed hypopituitarism (decreased ACTH, TSH), renal dysfunction and hypercalcemia. A variety of antibiotics, acyclovir and gamma-globulin failed to improve her symptoms. A diagnosis of Chlamydia trachomatis infection was considered from the elevated antibody titers. In this case, minocycline was very effective. Rarely Chlamydia trachomatis infection involved general organs, including the central nervous system. It was interesting that she had endocrine disorders. We must take a look for Chlamydia trachomatis infection because this infection infrequently involves general organs, including the central nervous system and minocycline is very effective for this infection.

Adult↗