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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 505 records · Page 28Linked to original sources
PubMed1992

[Analysis of the GPIIb and GPIIIa genes in patients with Glanzmann's thrombasthenia].

Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder due to a deficiency or abnormality of glycoproteins (GPs) IIb and IIIa, but its genetic basis remains to be determined. We analyzed the genes for GPIIb and 3'GPIIIa in 3 patients with GT and in 7 control subjects by Southern blot. No large deletions or insertions were detected in these genes in any patient with GT. Furthermore, the GPIIb and GPIIIa mRNAs derived from the platelets of patients with GT could be amplified using the reverse transcriptase-polymerase chain reaction (RT-PCR). This finding indicates that the mRNAs of the patients with GT are considered to be normally transcribed. The molecular defects of the GPIIb.

Blotting, Southern↗
PubMed1991

Suppressive effects of L-5-hydroxytryptophan in a feline model of photosensitive epilepsy.

We recently demonstrated that long-lasting photosensitivity is acquired as a result of kindling of the lateral geniculate nucleus (LGN), and that the LGN-kindled cat pretreated with D, L-allylglycine represents a useful model of epilepsy for drug studies. The present experiments studied anticonvulsant effects of a serotonin precursor, L-5-hydroxytryptophan (5-HTP), on photosensitivity in the LGN-kindled cat under D,L-allylglycine and on LGN-kindled seizures. 5-HTP suppressed both myoclonic responses and paroxysmal EEG discharges induced by photic stimulation in a dose-related manner. Photically-induced seizures were completely blocked 1.5-2 h after injection of 20 mg/kg 5-HTP. 5-HTP was also effective in reducing the afterdischarge duration and behavioral seizure stage in LGN-kindled seizures; following 40 mg/kg administration, no electroclinical seizures were elicited in the LGN-kindled cats. Serotonergic mechanisms may play an important role in epileptic photosensitivity; the 5-HTP suppressive effect on photosensitivity is at least partly due to reduced neuronal activity at the level of the LGN via serotonergic inhibition.

5-Hydroxytryptophan↗
PubMed1991

The complete primary structure of the human alpha 1 (VIII) chain and assignment of its gene (COL8A1) to chromosome 3.

Type VIII collagen molecules, expressed by corneal and vascular endothelial cells, appear to be heterotrimers composed of two genetically distinct polypeptides, alpha 1 (VIII) and alpha 2(VIII), in the ratio of 2:1. Characterization of the rabbit alpha 1(VIII) gene has demonstrated that it consists of only four exons, one of which is large and encodes the entire triple-helical and carboxyl non-triple-helical domains. A similar exon organization has been found for the chicken alpha 1(X) and the mouse and human alpha 2(VIII) collagen genes. The genes encoding alpha 1(VIII), alpha 2(VIII), and alpha 1(X) collagen chains are therefore homologous members of a unique class of genes within the collagen superfamily. In the present paper we describe for the first time the primary structure of the human alpha 1(VIII) collagen chain, based on isolation and sequencing of a genomic DNA fragment. The results indicate that the human alpha 1(VIII) chain has the same domain structure as the rabbit protein. We also demonstrate that the gene is localized on the long arm of the human chromosome 3. The availability of genomic DNA encoding the human alpha 1(VIII) collagen chain and information about its chromosomal location should make it possible to examine whether hereditary diseases are linked to abnormalities in the structure or expression of the alpha 1(VIII) gene.

Amino Acid Sequence↗
PubMed1991

Characterization of the human IL-5 receptors on eosinophils.

Interleukin 5 (IL-5) receptors on the cell surface of human eosinophils and other hematopoietic cells were characterized using radiolabeled recombinant IL-5. The binding of 35S-labeled murine IL-5 to eosinophils from normal human peripheral blood was rapid and saturable within a 30-min incubation at both 4 and 37 degrees C. The binding of 35S-labeled murine IL-5 to eosinophils was inhibited by an excess of unlabeled murine and human IL-5 or by an anti-murine IL-5 monoclonal antibody (NC17) but not by other human cytokines. Scatchard plot analysis revealed that human eosinophils have a single class of high affinity receptor (Kd 170-330 pM; number of binding sites: 260-380/cell). IL-5 receptors on eosinophils from four patients with eosinophilia displayed similar characteristics. Affinity cross-linking experiments resulted in the identification of human IL-5 receptor on eosinophils with a molecular mass of 55-60 kDa. Among the various cells besides eosinophils and cell lines that we could test, a subline of HL-60 (YY-1 cells) was found to display a significant number of IL-5 receptor. These results suggest that IL-5 may act on limited types of cells in the human system.

Aged↗
PubMed1991

The alpha 1 (VIII) collagen gene is homologous to the alpha 1 (X) collagen gene and contains a large exon encoding the entire triple helical and carboxyl-terminal non-triple helical domains of the alpha 1 (VIII) polypeptide.

We recently cloned and sequenced alpha 1 (VIII) collagen cDNAs and demonstrated that type VIII collagen is a short-chain collagen that contains both triple helical and carboxyl-terminal non-triple helical domains similar to those of type X collagen (Yamaguchi, N., Benya, P., van der Rest, M., and Ninomiya, Y. (1989) J. Biol. Chem. 264, 16022-16029). We report here on the structural organization of the gene encoding the rabbit alpha 1 (VIII) collagen chain. The alpha 1 (VIII) gene contains four exons, whose sizes are 69, 120, 331, and 2278 base pairs. The first and second exons encode only 5'-untranslated sequences, whereas the third exon codes for a very short (3 nucleotides) stretch of 5'-untranslated sequence, the signal peptide, and almost the entire amino-terminal non-triple helical (NC2) domain (109 1/3 codons). Interestingly, the last exon encodes the rest of the translated region, including 7 2/3 codons of the NC2 domains, the complete triple helical domain (COL1, 454 amino acid residues), the entire carboxyl-terminal non-triple helical domain (NC1, 173 amino acid residues), and the 3'-untranslated region. This exon-intron structure is in stark contrast to the multi-exon structure of the fibrillar collagen (types I, II, III, V, and XI) genes, but it is remarkably similar to that of the type X collagen gene (LuValle, P., Ninomiya, Y., Rosenblum, N. D., and Olsen, B. R. (1988) J. Biol. Chem. 263, 18278-18385). The data suggest that the alpha 1 (VIII) and the alpha 1 (X) genes belong to the same subclass within the collagen family and that they arose from a common evolutionary precursor.

Amino Acid Sequence↗
PubMed1991

Platelet factor 4 mRNA expression in cells from a patient with megakaryoblastic crisis of chronic myelogenous leukemia.

A 61-year-old man with Philadelphia chromosome-positive chronic myelogenous leukemia developed megakaryoblastic leukemia. In the blast phase, his blast cells showed undifferentiated megakaryoblastic characteristics with no alpha-granules or demarcation membranes but with detectable platelet peroxidase (PPO) activity and surface glycoprotein (GP) IIb/IIIa. The patient has remained reasonably well for at least 12 months after blastic crisis, and 6-mercaptopurine alone has been effective in controlling leukocytosis and megakaryoblast proliferation. The expression of mRNA for platelet-specific proteins, such as GPIIb and platelet factor 4 (PF4), was studied in the patient's blast cells by the Northern blot analysis. Both GPIIb and PF4 mRNA were detected in the blast cells. Cytoplasmic maturation occurs later than the synthesis of the surface GP during megakaryocyte maturation. Therefore, PF4 mRNA expression should be a marker of mature megakaryoblasts. The PF4 mRNA expression in megakaryoblastic leukemia may indicate that a patient will have long survival and a good response to chemotherapy.

Antibodies, Monoclonal↗
PubMed1991

Identification of the second subunit of the murine interleukin-5 receptor: interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor.

Murine interleukin-5 (IL-5) binds to its receptor with high and low affinity. It has been shown that the high affinity IL-5 receptor (IL-5-R) is composed of at least two membrane protein subunits and is responsible for IL-5-mediated signal transduction. One subunit of the high affinity IL-5-R is a 60 kDa membrane protein (p60 IL-5-R) whose cDNA was isolated using the anti-IL-5-R monoclonal antibody (mAb), H7. This subunit alone binds IL-5 with low affinity. The second subunit does not bind IL-5 by itself, and is expressed not only on IL-5-dependent cell lines but also on an IL-3-dependent cell line, FDC-P1. Expression of the p60 IL-5-R cDNA in FDC-P1 cells, which do not bind IL-5, reconstituted the high affinity IL-5-R. We have characterized the second subunit of the IL-5-R by using another anti-IL-5-R mAb, R52.120, and the anti-IL-3-R mAb, anti-Aic-2. The anti-Aic-2 mAb down-regulated binding of IL-5 to an IL-5-dependent cell line, Y16. Both R52.120 and anti-Aic-2 mAbs recognized membrane proteins of 130-140 kDa expressed on FDC-P1 and Y16 cells. The R52.120 mAb recognized both murine IL-3-R (AIC2A) and its homologue (AIC2B) expressed on L cells transfected with suitable cDNAs. The high affinity IL-5-R was reconstituted on an L cell transfectant co-expressing AIC2B and p60 IL-5-R, whereas only the low affinity IL-5-R was detected on a transfectant co-expressing AIC2A and p60 IL-5-R.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Evaluation of cancer prevention strategies by computerized simulation model: an approach to lung cancer.

A computerized simulation model was developed to evaluate the potential impact of primary and secondary prevention on lung cancer mortality in Japan. The natural history of lung cancer was modeled as a Markovian stochastic process from cancer-free to preclinical, clinical, and finally to terminal states. The increase in mortality rate of lung cancer among males aged 75 to 79 years has been the major force of increase in the total number of lung cancer deaths in Japan. The simulation showed that this tendency would continue until the late 1990s, presumably due to the increase in the proportion of ever-smokers in that cohort, who started smoking at an earlier age than did prior generations. It was shown that the number of lung cancer deaths can be reduced either by smoking cessation or screening programs, and that the reduction is proportional to the increase in the annual smoking-cessation rate and to the annual increment in the screening rate. However, only two to three percent reduction of lung cancer deaths in the year 2001 can be expected when the annual smoking-cessation rate is raised from the current value of 0.46 percent to five percent during the period from 1991 to 2000 or when the screening rate is increased by three percent annually for the same period.

Adult↗
PubMed1991

Membranous lipodystrophy (Nasu-Hakola disease) with thalamic degeneration: report of an autopsied case.

An autopsied case of membranous lipodystrophy (Nasu-Hakola disease, NHD) with thalamic degeneration was reported. A 34-year-old Japanese man was diagnosed as having NHD by bone biopsy prior to the onset of clinical symptoms. His maternal grandfather and paternal grandmother are cousins, but this family history is negative for NHD. He developed frontal lobe syndrome at the age of 35 with progressive dementia, and died of acute renal failure at the age of 46. Gross inspection of the brain detected atrophy and softening of the cerebral white matter, predominantly in the frontal lobe. Microscopically, numerous spheroids, predominant fibrillary gliosis with less prominent demyelination "dissociation glio-myélinique" and scanty sudanophilic lipid droplets were observed, indicating the sclerosing type of NHD. An unusual patholgoical finding in this case was selective involvement of the thalamic nuclei with preservation of the other gray matter except for focal cortical necrosis. The topography of the affected thalamic nuclei is similar to that of systemic thalamus degeneration. An association with thalamic degeneration in NHD has not been previously reported. The present case suggests that NHD also affects the thalamus.

Adult↗
PubMed1991

Visual dysfunction in treated schizophrenia suggested by visual evoked potentials from pattern-reversal stimulation.

Steady-state visual evoked potentials (steady-state VEPs) from pattern-reversal stimulations were compared in treated schizophrenic patients and normal subjects matched for sex and age. The VEP amplitudes were more variable in the patients than in the controls. Furthermore, the VEP amplitudes of the patients mostly showed little or no change when the check size was varied, in contrast to the controls who showed a marked check size effect. These results suggest that schizophrenics receiving drugs have dysfunction of the visual system, especially an inability to respond adequately to changes of visual information.

Adult↗
PubMed1991

Morphometric study on the CH4 of the nucleus basalis of Meynert in Alzheimer's disease.

Ch4 neurons were studied morphometrically in three normal controls and three patients with Alzheimer's disease (AD). Two series of preparations stained with cresyl violet and with the indirect immunoperoxidase method using a monoclonal antibody to acetylcholinesterase (AChE) counterstained with cresyl violet were morphometrically analyzed. The cholinergic neurons were identified as positive reaction products of AChE in the perikarya. The cross-sectional area of all the Ch4 neurons with clearly visible nucleoli in one preparation was measured using a computer imaging system. Evaluation of these data provided a mean value of the cross-sectional neuronal area (CNA), number of neurons, standard deviation of the CNA and coefficient of variation of the cholinergic and noncholinergic neurons. The cholinergic neurons were decreased in number but showed hypertrophy in the early stage of AD, and they gradually became atrophic in the advanced stage. The noncholinergic neurons showed only atrophy without definite neuronal cell depletion. These findings indicate that cholinergic neurons have a plasticity and remodeling property against the AD process and suggest that hypertrophy of the cholinergic neurons in the Ch4 is the result of the effect of neurotrophic factors.

Acetylcholinesterase↗
PubMed1991

Myocardial dysfunction and norepinephrine release in the isolated rat heart injured by electrolysis-induced oxygen free radicals.

In the present investigation, we used electrolysis as a source of oxygen free radicals to test their possible role in norepinephrine release, as well as in the mechanism of cellular injury, cardiac dysfunction and arrhythmias. In the isolated rat heart perfused under constant pressure, according to the Langendorff technique, electrolysis of the Krebs-Henseleit solution (10 mA d.c. current for 1 min) produced myocardial irreversible dysfunction within 5 min. Fifteen minutes after electrolysis, significant falls in the left ventricular pressure (from 87.5 +/- 6.8 to 33.7 +/- 5.2 mmHg), dP/dt max (from 1230 +/- 90 to 375 +/- 59 mmHg/s), heart rate (from 287 +/- 18 to 119 +/- 13.5 beats/min) and coronary flow (from 14.8 +/- 9 to 3.4 +/- 1.7 ml/min) were observed, along with an increase in left ventricular end diastolic pressure from 10 to 50 +/- 3.5 mmHg (n = 8, P less than 0.01). AV conduction block and/or sinus bradycardia were noted in all preparations. An increase in norepinephrine washout from 298.5 +/- 84 at baseline to 610 +/- 110 pg/min/g 5 min after electrolysis was measured (n = 8, P less than 0.05) and a 44.8 +/- 9.2% and 35 +/- 7.5% reduction, respectively in right and left ventricular tissue norepinephrine content was also found at 30 min (n = 5, P less than 0.05). Pretreatment of the hearts 10 min before electrolysis and throughout the experimental period by superoxide dismutase (SOD; 100 U/ml), catalase (150 U/ml), a combination of SOD + catalase or mannitol (50 mM) partially blocked the deleterious effect of free radicals and permitted a functional recovery of 50 to 60%, mannitol being the more potent protective agent. Furthermore, these scavengers also significantly reduced norepinephrine washout.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Inhibitory effect of MK-801 (noncompetitive NMDA receptor antagonist) on kindling-induced synaptic potentiation in acutely prepared rabbits.

We investigated effects of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, on potentiation of field potentials elicited in the dentate gyrus by single shocks to the perforant path after kindling to the pathway in acutely prepared rabbits. MK-801, which was intracortically injected after the establishment of kindling-induced potentiation, remarkably and dose-dependently reduced the potentiation. These results suggest that activated NMDA receptors contribute substantially to the expression of kindling-induced potentiation.

Animals↗
PubMed1991

In vivo administration of antibody to murine IL-5 receptor inhibits eosinophilia of IL-5 transgenic mice.

We investigated the in vivo role of interleukin 5 (IL-5) and its receptor (IL-5R) in eosinophil growth and differentiation. When mice were administered IL-5 i.p., an increase in the number of eosinophils was observed within 5 days in peripheral blood and the peritoneal cavity. Hypereosinophilia was observed in IL-5 transgenic mice who displayed constitutive production of IL-5. A binding assay with 35S-labeled IL-5 revealed the presence of two classes of IL-5 binding sites (low and high affinity) on the surface of eosinophils. IL-5Rs on eosinophils were recognized using mAbs against murine IL-5R. When the IL-5 transgenic mice were passively administered with anti-murine IL-5R mAbs, the number of recognizable eosinophils in peripheral blood dropped within 5 days to normal levels. The antibody treatment also prevented the increase in the number of eosinophils in IL-5-injected mice. The inhibition of the above experimental eosinophilia was also observed by the passive administration of anti-IL-5 mAb. The results of the in vivo experiments clearly demonstrate that IL-5 plays an essential role in in vivo eosinophilopoiesis and may be acting on eosinophils or their precursors directly through IL-5Rs, resulting in preferential growth of this lineage of hematopoietic cells. It can also be stressed that IL-5 regulates a specific lineage of hematopoietic cells (eosinophils).

Animals↗
PubMed1991

Molecular characterization of the beta chain of the murine interleukin 5 receptor.

Interleukin 5 (IL-5) is a multifunctional cytokine that regulates the proliferation and differentiation of hematopoietic cells including B cells and eosinophils. The murine IL-5 acts on target cells via an IL-5 specific high-affinity receptor (Kd approximately 150 pM) that has been proposed to be composed of at least two membrane polypeptide chains. The p60 component recognized by anti-murine IL-5 receptor mAbs H7 and T21 binds IL-5 with low affinity (Kd approximately 10 nM). The other component is p130, detectable by following cross-linking experiments with IL-5. Using H7, T21, and R52.120 mAbs specific to murine IL-5 receptor, we characterized the molecular nature of the p130 of the high affinity receptor for murine IL-5. R52.120 mAb did not recognize the IL-5 binding recombinant p60 expressed on COS7 cells, but reacted with p130/140 on IL-5-dependent cell lines. R52.120 mAb showed partial inhibition of the IL-5-induced proliferation of the IL-5-dependent early B cell line Y16 at high IL-5 concentrations. Addition of R52.120 mAb together with H7 or T21 mAb caused more striking inhibition of the IL-5-dependent proliferation than that caused by either of them alone. R52.120 mAb down-regulated the number and dissociation constant of IL-5 binding sites with high affinity without affecting the levels of these with low-affinity. It also preferentially inhibited the formation of the cross-linked complex of p130 with radiolabeled IL-5. These results indicate that p130/p140, recognized by R52.120 mAb, is indispensable, together with p60, for the formation of high affinity IL-5 receptor. We propose to designate p60 and p130/p140 as the alpha and beta chain of IL-5 receptor, respectively.

Animals↗
PubMed1991

Murine interleukin 5 receptor isolated by immunoaffinity chromatography: comparison of determined N-terminal sequence and deduced primary sequence from cDNA and implication of a role of the intracytoplasmic domain.

The murine interleukin 5 receptor (IL-5R) was identified by utilizing an immobilized IL-5 and an immobilized monoclonal antibody against the murein IL-5R (designated H7 mAb). The H7 mAb immunoaffinity-purified materials from the extract of cell-surface radioiodinated T88-M cells (an IL-5-dependent early B cell line) using 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) were reacted with an immobilized IL-5 matrix. SDS-PAGE of the adsorbed fraction revealed a single band at approximately 60 kDa. The binding of the 60 kDa protein to the immobilized IL-5 matrix was inhibited by the excess IL-5. The CHAPS-extract depleted of the 60 kDa protein by the absorption with H7 mAb did not contain any IL-5 binding proteins. Immunoaffinity procedure provided a final 7400-fold purification, based on an estimation of the content of the 60 kDa protein (approximate purity: 20%) from the silver-stained pattern of SDS-PAGE. Actin was copurified with the 60 kDa protein at an approximate ratio of 1:1, suggesting that the intracytoplasmic domain of the IL-5R may interact with actin. Furthermore, soluble IL-5R (molecular mass: 50 kDa) was purified by the H7 mAb-immunoaffinity chromatography. The purified soluble IL-5R was capable of inhibiting the binding of IL-5 to T88-M cells. Preparative SDS-PAGE followed by electroblotting onto a membrane permitted the determination of the N-terminal sequence of the IL-5R. The determined N-terminal sequence of the IL-5R and the deduced primary sequence from recently isolated cDNA were compared.

Actins↗
PubMed1991

Detection of human antibody against the human papillomavirus type 16 E7 protein.

We examined 500 human sera for the presence of antibody against the human papillomavirus type 16 E7 protein by enzyme-linked immunosorbent assay with bacterially expressed fusion protein lac-E7, and by radioimmunoprecipitation and immunofluorescence assays with the E7 protein expressed in monkey COS-1 cells. The anti-E7 antibody was detectable in 6 out of 54 cases of cervical carcinoma, but in none of the others, including patients with other gynecologic cancers, those with sexually transmitted diseases, and healthy adults. The data indicate that expression of the E7 protein is closely related to cervical carcinoma.

Animals↗