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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 379 records · Page 21Linked to original sources
PubMed1993

Propentofylline (HWA285) inhibits the release of dopamine during transient ischemia and modulates its metabolism in rat striatum.

Propentofylline (HWA285) has been reported to protect neuronal cells through the inhibition of glutamate release during transient ischemia. We studied whether HWA285 inhibits dopamine (DA) release, and how HWA285 modulates DA metabolism in the rat model. HWA285 was perfused through a microdialysis probe placed in the rat striatum during 20 min transient ischemia. In rats perfused by HWA285, ischemic DA release was significantly inhibited, and DA metabolism showed better recovery in contrast with unperfused rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Human recombination activating gene-1 in leukemia/lymphoma cells: expression depends on stage of lymphoid differentiation defined by phenotype and genotype.

The recombination activating gene, RAG-1, which is supposed to encode a molecule regulating V(D)J recombination, has been isolated. In the current study, the distribution of RAG-1 expression in human neoplastic hematopoietic cells was compared with the phenotypic and genotypic status of differentiation. Thirty-one hematopoietic cell lines (16 B-lineage, 9 T-lineage, 2 Hodgkin's disease, and 4 nonlymphoid cell lines) were investigated for the expression of human RAG-1 using the reverse-transcriptase polymerase chain reaction (RT-PCR). RAG-1 was not expressed in nonlymphoid, Hodgkin's disease, or mature-stage lymphoid cell lines, but was present in some acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) cell lines. The investigation was extended to 45 cases of fresh ALL/LBL cells. The patterns of RAG-1 expression found in the cell lines and fresh ALL/LBL cells were similar. In B-lineage cells, the product of RAG-1 RT-PCR was detected in CD19+ CD10- CD20- CD5- stage (stage II, Nadler's classification) and was at the highest level in CD19+ CD10+ CD20- CD5- stage (stage III), but was absent or limited in CD19+ CD10+ CD20-+ CD5- (stage IV) or CD19+ CD10+ (or CD10-) CD5+. In stage II, monoclonal gene rearrangements of only the immunoglobulin heavy chain (IgH) were found, whereas monoclonal gene rearrangements of both IgH and T-cell receptor (TCR)-beta chain were frequently noted in stages III and IV. The expression of CD20 or CD5 antigen apparently correlated with the decline of RAG-1 expression. In T-lineage cells, RAG-1 was highly expressed in CD3- CD4+ CD8+/CD3+ CD4+ CD8+ thymic stages, but was negative or only weakly expressed in the CD3- CD4- CD8- prothymic or early thymic stage, in which the TCR-beta gene was often germline, or the CD3+ CD4+ CD8- mature thymic stage. The relative levels of RAG-1 mRNA give an additional delineating frame to the schemes of lymphoid differentiation based on phenotypic and genotypic status. RAG-1 is exhibited by cells of the thymic stage capable of synthesizing TCR or expressing it on the cell surface. The weak or absent expression of RAG-1 in the prothymic or early thymic stage suggests that the contribution of RAG-1 to the gene rearrangement may differ quantitatively between TCR-delta/TCR-gamma and TCR-beta.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗
PubMed1993

Visualization of the morphology of purple membrane surfaces by monoclonal antibody techniques.

A monoclonal antibody technique for determining the surface morphology of the purple membrane (PM) has been developed. Two types of antibodies for distinguishing the extracellular surface and the cytoplasmic surface of PM were produced by immunizing the corresponding synthetic peptides to mice. The Langmuir-Blodgett (LB) method was employed to form a single-layer two-dimensional array of PM fragments on an electron microscope grid. The LB film was then treated with the antibodies which had been labeled with colloidal gold particles. Electron microscope observations visualized the morphology of the two surfaces of PM to be rough and smooth regions, respectively; thus the orientation of PM fragments was determined.

Amino Acid Sequence↗
PubMed1993

Increased tumor localization by monoclonal antibody A7 after F(ab')2 fragmentation in athymic nude mice bearing human pancreatic carcinomas.

Much recent research has been directed toward the use of monoclonal antibodies (MoAbs) for the immunodetection of solid tumors. In pancreatic cancer, conventional immunoscintigraphy using intact MoAbs remains disappointing. In this study, 125I-labeled F(ab')2 fragments produced by pepsin digestion of MoAb A7 were injected intravenously into nude mice bearing human pancreatic cancer, HPC-YS, xenografts that have previously been shown to react specifically with MoAb A7. The tumor tissue/blood ratio of 125I-labeled F(ab')2 fragments of MoAb A7 increased with time and was much higher than those for normal tissues. Moreover, the tumor tissue/blood ratio of 125I-labeled F(ab')2 fragments was greater than that of intact MoAb A7, although the F(ab')2 accumulation was less than that of intact MoAb A7 in the tumor. These results suggest that F(ab')2 fragments of MoAb A7 may be suitable carriers of radionuclides for immunodetection of human pancreatic cancer.

Animals↗
PubMed1993

Intratumoral administration of neocarzinostatin conjugated to monoclonal antibody A7 in a model of pancreatic cancer.

We investigated the following in athymic nude mice with xenografts of a human pancreatic carcinoma: 1) clearance of the murine monoclonal antibody A7 from the carcinoma; and 2) the antitumor effect of neocarzinostatin conjugated to MAb A7 (A7-NCS) on the carcinoma following intratumoral injection. Compared with 125I-labeled normal mouse IgG, a significantly larger amount of 125I-labeled A7 remained in the tumor after intratumoral injection. Neocarzinostatin conjugated to MAb A7 showed a greater antitumor activity against human pancreatic cancer than neocarzinostatin alone after intratumoral administration. The conjugate completely suppressed tumor growth macroscopically during the experiment. Tumor tissue in mice became necrotic 32 days after injection with A7-NCS. These observations suggest that the intratumoral injection of A7-NCS offers promise in treating pancreatic carcinoma.

Animals↗
PubMed1993

The Gogi (word-meaning) syndrome with impaired kanji processing: alexia with agraphia.

Two cases, one with probable Pick's disease and one with herpes simplex encephalitis, are presented, focusing on Gogi (word-meaning) aphasia-like syndrome as their salient clinical feature. Their aphasic symptoms were characterized by impaired kanji processing and preserved kana processing in writing and oral reading known as a defining feature of Gogi aphasia, but little evidence of so-called "phonetic use of kanji in writing" and "confusion between on- and kun-readings of kanji in oral reading" often observed in Gogi aphasia. Systematic neuropsychological test batteries administered to them showed that the selective impairment of kanji processing did not always arise from a disturbance of a specific ability known to be essential to Gogi aphasia (i.e., failure in comprehending the semantic content of spoken and written language), but rather from an amnestic disruption in the ability to access the correct orthographic and phonological forms of kanji words. This selective impairment of kanji processing may be compatible with "alexia with agraphia of kanji," recently known to be attributable to left posterotemporal lesions. These results suggest that Gogi aphasia (or similar syndromes) is not necessarily a real syndrome but a polytypic constellation of symptoms.

Adult↗
PubMed1993

Deletion analysis of a replication origin of human cytomegalovirus by a novel assay system with a combination of microinjection and polymerase chain reaction.

We have developed a sensitive assay for DNA replication in mammalian cells that enables us to detect replicated DNA fragments of human cytomegalovirus. A 1/100 portion of DNA extracted from 1000 microinjected cells was subjected to polymerase chain reaction after digestion with appropriate restriction enzymes to differentiate replicated from nonreplicated plasmids. A portion of the amplified DNA was electrophoresed to detect replicated DNA. Subfragments of the HindIII fragment A (24 kb, map units 0.37-0.47) of strain Towne, which contains a previously identified origin of DNA replication (oriLyt), were analyzed by the assay system. A 4.3-kb subfragment (AatII-SacI) replicated as efficiently as the HindIII fragment A. Efficient replication ability was lost with a 1.3-kb deletion from the AatII end or a 0.9-kb deletion from the SacI end. These results suggest that the boundaries of oriLyt of Human cytomegalovirus strain Towne lie within the 1.3- and the 0.9-kb regions of the 4.3-kb fragment.

Base Sequence↗
PubMed1993

A quantitative magnetic resonance imaging study of patients with schizophrenia.

Twenty patients with schizophrenia and ten normal control subjects underwent magnetic resonance imaging of the brain. The volumes of several brain structures were measured using a computer image analysing system. The schizophrenic patients had significantly smaller left parahippocampal volume and larger left temporal horn volume than the control subjects. A larger body of the right lateral ventricle could be estimated in the schizophrenics, but this difference was not significant. In the patient group a non-significant negative correlation was established between the presence of positive symptoms and the left temporal horn volume. There was no significant correlation between the temporal horn and temporal lobe or medial temporal structures. Our results indicate that the left medial temporal structure or left temporal lobe may be involved in schizophrenia and that temporal horn enlargement does not simply represent volume loss of the surrounding tissue.

Adult↗
PubMed1993

Antioxidant protection against oxidant-induced damage in cultured gastric mucosal cells.

Gastric epithelium is exposed not only to oxidants generated within the lumen, but also to those produced by ischemia/reperfusion. This study examined the mechanism(s) of oxidant-induced injury to cultured rat gastric mucosal cells, and characterized the antioxidant profile of these cells. Hydrogen peroxide (H2O2), generated by glucose oxidase, damaged cells dose-dependently, as assessed by increased leakage of labeled 51Cr. Glucose oxidase-induced damage was prevented by exogenous catalase (but not by exogenous superoxide dismutase). Chelation of cellular iron with desferrioxamine or phenanthroline specifically protected cells against H2O2, whereas binding of extracellular iron with apotransferrin failed to. Disruption of the glutathione redox cycle at three independent sites rendered cells less resistant to H2O2, whereas inhibition of cellular catalase did not result in sensitization of cells to H2O2. In conclusion, (1) oxidant injury induced by extracellular H2O2 is mediated by intracellular iron; (2) extracellular superoxide is not involved in the damaging process; and (3) the glutathione redox cycle plays a principal role in detoxifying H2O2 as a cellular antioxidant in cultured gastric mucosal cells.

Animals↗
PubMed1993

Haloperidol-induced blockade of induction of long-term potentiation in perforant path-dentate gyrus pathway in chronically prepared rabbits.

We investigated the effects of the representative neuroleptic and dopamine receptor antagonist haloperidol (HPD) on the induction of long-term potentiation (LTP) or on the previously induced LTP in the perforant path-dentate gyrus pathway in chronically prepared rabbits. The IP HPD injection of 0.8 mg/kg blocked the induction of LTP when it was given before LTP-inducing tetanic stimulations, although this dose showed virtually no effect on the baseline control responses in the perforant path-dentate gyrus pathway to single shocks. However, neither 0.8-mg/kg nor 1.6-mg/kg HPD doses affected the previously induced LTP. The possible mechanisms underlying these results, notably the HPD-induced blockade of LTP induction, are discussed, especially in association with the inhibitory action of HPD on calmodulin-mediated events rather than dopaminergic function.

Animals↗
PubMed1993

SPECT analysis of regional cerebral blood flow changes in patients with schizophrenia during the Wisconsin Card Sorting Test.

Single photon emission computed tomography (SPECT) images were obtained in 10 right-handed neuroleptic-treated schizophrenic patients and 10 healthy volunteers using Tc-99m-hexamethyl-propylenamine oxime (Tc99m-HMPAO) during performance of the Wisconsin Card Sorting Test (WCST) and at rest. None of the patients showed severe impairment on the WCST. The patient group showed a statistically insignificant trend to incur more unique errors. In both the patient and control groups, the left lateral prefrontal blood flow significantly increased during the WCST, as compared to during resting conditions. Only during the WCST, the patient group showed a significant regional cerebral blood flow (rCBF) decline in the left medial prefrontal cortex, as well as in the right side under both the test and resting conditions. This left medial prefrontal rCBF during the WCST correlated positively with the number of unique errors, although this correlation was statistically insignificant. The right fronto-parietal rCBF was significantly increased in the patient group under both the test and resting conditions. Moreover, in the left hippocampal region, the patient group showed a significant rCBF increase under resting conditions.

Adult↗
PubMed1993

Pattern of expression of CD45 RA/RO isoformic antigens in acute myeloblastic leukemia cells.

The authors used cell surface immunofluorescence to investigate the expression of CD45 RA (4KB5)/RO (UCHL1) antigen by acute myeloblastic leukemia (AML) cells from 78 patients. Four types--RA+/RO- (RO < 15%), RA-/RO+ (RA < 15%), mixed (20% RA and 20% RO), and RA-/RO- (RA < 10% and RO < 10%)--were observed. The number of cases with RA+/RO-, RA-/RO+, mixed, and RA-/RO- types in each French-American-British subclass of AML were as follows: M1 (n = 22): 18, 4, 0, 0; M2 (n = 21): 16, 0, 5, 0; M3 (n = 14): 11, 0, 0, 3; M4: 2, 2, 1, 0; and M5: 5, 5, 6, 0, respectively. The M1 RA-/RO+ type, which was always CD7- CD34- HLA-DR-, constituted a rare and distinct M1 subtype because there was no mixed type among the M1 cases. All CD7+ AML cells were the RA+/RO- type and HLA-DR+ except one. The expression of CD45 RO antigen, found in patients with M2, M4, and M5 subtypes of AML, was thought to be associated with the maturity of blasts as monocyte or granulocyte lineage cells. CD45 antigen has tyrosine phosphatase activity in association with nonreceptor-type tyrosine kinases. It was speculated that the functional status and stage of differentiation of the granulocyte/monocyte lineage determine which type of nonreceptor-type tyrosine kinases will operate, which then select the pattern of expression of the CD45 isoform. Thus, the determination of tyrosine kinases associated with CD45 isoforms seems to be important in understanding the AML subsets defined by the pattern of CD45 RA/RO expression.

Adolescent↗
PubMed1993

Role of presynaptic beta 2-adrenergic facilitation in the development and maintenance of DOCA-salt hypertension.

The present study evaluated the contribution of the presynaptic beta 2-adrenergic facilitation in the increase of plasma norepinephrine levels observed in deoxycorticosterone acetate (DOCA)-salt hypertension. Epinephrine is thought to be the major endogenous activator of this presynaptic mechanism and although basal epinephrine levels were similar in normotensive and DOCA-salt hypertensive rats, the sensitivity of the presynaptic beta 2-adrenergic facilitatory mechanism was found to be increased in hypertensive animals. This was shown in vivo by the enhanced plasma norepinephrine increases induced by a direct presynaptic stimulation with a selective beta 2-adrenergic receptor agonist. Furthermore, the adrenal medulla was hyperreactive in response to a hemorrhagic hypotension of 50 mm Hg, as shown by a greater plasma epinephrine increase in DOCA-salt-treated rats, and tissue concentrations of epinephrine were found to be greatly increased in the aorta of hypertensive animals. The possible contribution of epinephrine activation of the presynaptic beta 2-adrenergic mechanism on the development and maintenance of DOCA-salt hypertension was assessed by evaluating the effects of chronic or acute adrenalectomy, respectively. Acute adrenalectomy decreased significantly the blood pressure only in hypertensive animals, whereas chronic adrenalectomy abolished the plasma norepinephrine and blood pressure differences between normotensive and DOCA-salt-treated rats. The present results therefore suggest that the presynaptic beta 2-adrenergic facilitation is exaggerated in DOCA-salt hypertension, mainly due to an increased sensitivity of this mechanism and to a hyperreactivity of the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1993

Purification and characterization of UDP-N-acetylglucosamine: alpha-6-D-mannoside beta 1-6N-acetylglucosaminyltransferase (N-acetylglucosaminyltransferase V) from a human lung cancer cell line.

A beta 1-6N-acetylglucosaminyltransferase (GnT-V) [EC 2.4.1.155] which catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to alpha-D-6-mannoside has been purified up to 20,000-fold from the cultured supernatant of the QG small lung cancer cell line with a 37% yield. The isolation procedure included chromatography on phenyl-Sepharose, hydroxylapatite, UDP-hexanolamine Sepharose, and a biantennary sugar substrate (GnGn-bi-Asn) coupled to activated CH-Sepharose 4B. Sodium dodecyl sulfate gel electrophoresis under non-reducing conditions showed a single band of 73 kDa. Under reducing conditions, however, an additional component of 60 kDa was seen. Peptide mapping analysis indicated that both of these proteins were essentially identical, indicating that the 60-kDa component is probably a proteolytically cleaved form of the 73-kDa protein. Studies on the activity of the enzyme toward a variety of pyridylaminated sugars showed that the enzyme is most active toward triantennary (GnGnGn-tri-PA) and biantennary (GnGn-bi-PA) sugars. The Km values for GnGn-bi-PA and UDP-GlcNAc were 133 microM and 3.5 mM, respectively. These studies represent the first report of the enzymatic properties of a highly purified human GnT-V.

Acetylglucosamine↗
PubMed1993

Lung cancer incidence rate for male ex-smokers according to age at cessation of smoking.

Lung cancer incidence rate after the cessation of smoking was assessed for male ex-smokers according to the age at cessation, using the results from a case-control study for ex-smoker versus continuing smoker, and the lung cancer incidence rate function for continuing smoker estimated from Japan Vital Statistics and the "Six-prefectural Cohort Study" in Japan. This hospital-based case-control study consisted of 776 lung cancer cases (553 current smokers and 223 ex-smokers) and 772 controls (490 current smokers and 282 ex-smokers) who started smoking at ages 18-22. The odds ratio of developing lung cancer for ex-smokers compared to continuing smokers according to years since the cessation of smoking was estimated for four age groups (55-64, 60-69, 65-74 and 70-79). Given that the number of years since cessation of smoking is the same, reduction of the odds ratio appeared to be greater for the younger age group than for the older age group, reflecting the shorter period of exposure for the younger age group. Lung cancer incidence rate (per 100,000) was assumed to be expressed by the following function; 1.7 x 10(-5) x (age -24.3) for continuing smokers and 0.15 x 10(-5) x (age) for nonsmokers. Lung cancer incidence rate among ex-smokers according to years since cessation was then estimated to be the above function multiplied by the odds ratio from the case-control study for each age group. In contrast to the greater reduction of the odds ratio among younger ex-smokers, reduction of the incidence rate, in terms of rate difference, was considerably greater for older ex-smokers due to a high incidence rate of lung cancer for older continuing smokers. This indicates that the absolute magnitude of reduction of the lung cancer incidence rate after cessation of smoking is greater for older ex-smokers, although the relative magnitude of reduction is greater for younger ex-smokers.

Age Factors↗
PubMed1993

Enhanced tumor localization of radiolabeled Fab fragments of monoclonal antibody A7 in nude mice bearing human pancreatic carcinoma xenografts.

Much recent research has been directed toward the use of monoclonal antibodies (MAb) for the immunodetection of solid tumors. In pancreatic cancer, the results of conventional immunoscintigraphy using intact MAb remain disappointing. Clear immunoscintigraphy with radiolabeled MAb requires a high tumor tissue/blood ratio of radioactivity and a low normal tissue/blood ratio of radioactivity. In this study, 125I-labeled Fab fragments produced by papain digestion of MAb A7 were injected intravenously into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft previously shown to react specifically with MAb A7. The radioactivity of tumors and normal organs was subsequently measured. The tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was 1.00 +/- 0.24 and 9.68 +/- 2.54 at 2 and 24 h after injection, respectively. The tumor tissue/blood ratio of radioactivity was significantly higher than those of normal organs at 24 h after injection. Moreover, the tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was greater than that of intact MAb A7, although the 125I-labeled Fab accumulation level was much less than that of 125I-labeled intact MAb A7 in the tumor. When mice bearing tumors which did not react with MAb A7 were studied, 125I-labeled Fab fragments did not specifically localize to the tumors. These results suggest that Fab fragments of MAb A7 may be suitable carriers of radionuclides for the immunodetection of human pancreatic cancer.

Animals↗
PubMed1993

Paradoxical GABAergic facilitation on seizure development observed from bicuculline-induced effects on visual cortical kindling at short interstimulus intervals in chronically prepared rabbits.

To investigate the influence of GABAergic function on seizure development, the effects of bicuculline, a GABAa receptor antagonist, on visual cortical and hippocampal kindling were examined in chronically prepared rabbits. Kindling-inducing stimulations were repeated at 5-min intervals. The changes in afterdischarge (AD) durations were compared before and 30 min after a low (2 mg/kg) and high dose (5 mg/kg) i.p. injection of bicuculline solution. In the visual cortical kindling group, the AD durations were markedly shortened after the low dose bicuculline injection, while bicuculline produced a prolongation of the AD durations in the visual cortical with the high dose injection and hippocampal kindling groups. The low dose bicuculline-induced inhibition of visual cortical kindling suggests facilitative GABAergic action on seizure development, while the drug-induced enhancement in the other groups reflects the well-known inhibitory GABAergic action.

Animals↗