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Biomedical subjects

M Sakaguchi

Publications and source records attributed to M Sakaguchi.

At least 379 records · Page 21Linked to original sources

[On schizophrenic cases which present neurosis-like symptoms from early childhood--in relation to the prodromal signs and childhood schizophrenia].

The concept of "childhood schizophrenia" is ambiguous because of problems on the diagnostic level, especially in regard to symptomatology and prognosis. After studies which produced the description of "early infantile autism", childhood schizophrenia studies were even more confused. One reason for this was that there were not sufficient follow-up studies about the schizophrenia-like psychoses during occurring childhood, on the one hand, and the retrospective-anamnestic research was limited in the field of adult psychiatry, on the other hand. The author has focused on two points of view in order to discuss the problem of childhood schizophrenia. One is the non outbreak of childhood psychoses in children from 6 to 8 years old which was demonstrated by a couple of epidemiological research studies. The other is the concept of "Knick" (in Germany) which usually accompanies classical German theories of schizophrenia. "Knick" means that, at some point in the patient's history, there is an incident that is the indication of the onset of schizophrenia. The subjects were selected from the author's own cases. They continuously and insidiously developed schizophrenic symptoms during pre-puberty and puberty, presenting behavioral abnormalities or neurosis-like signs from early childhood. The diagnostic criteria for schizophrenia corresponds to DSM-III and with the German theory of Bleuler and Schneider. All cases have been treated for more than ten years. The acute onset cases, the mentally retarded cases (DSM-III .318) and the cases with suspected organic brain disorders were excluded because of the diagnostic problems. The author could differentiate these subjects into three groups based on the development in the infantile stage. The first was autistic group and the second mentally subnormal (DSM-III .317) or borderline group. Psychiatric problems of these two groups were already obvious in early childhood. The third group developed normally until they were 3-5 years old. After that they presented neurotic symptoms having some kind of intra-familiar problems. The author could confirm that these three groups manifested various kinds of neurosis-like symptoms, mainly obsessive-compulsive ones, from 3-5 years old. The so-called latent time, which is thought to be a non-outbreak time of childhood psychoses, may correspond to the prodromal stage of schizophrenia in these cases. This research is based on study of 31 children. An in-depth study has been done by the author of 6 of these children, 2 in each of the 3 categories described above. The "Knick"-points were not identifiable in these cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Lack of evidence for infection of or effect on growth of hematopoietic progenitor cells after in vivo or in vitro exposure to human immunodeficiency virus.

The pathogenesis of the hematologic abnormalities commonly observed in patients with acquired immunodeficiency syndrome (AIDS) is incompletely understood. We report here that in vitro growth of myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells from six patients with AIDS was not significantly different from that of normal human immunodeficiency virus (HIV) seronegative donors: 25.3 +/- 5 CFU-GM per 5 x 10(4) low density marrow cells and 33.5 +/- 5 BFU-E were observed in AIDS patients versus 32.7 +/- 5 CFU-GM and 42.1 +/- 5 BFU-E in controls. Furthermore, no HIV-DNA in individual colonies (CFU-GM and BFU-E) could be detected using the polymerase chain reaction (PCR) technique, although HIV-1 DNA was detected in peripheral blood mononuclear cells from the same patients. Similarly, normal bone marrow cells exposed in vitro to different isolates of HIV or recombinant purified HIV-1 envelope glycoprotein (gp) 120 did not exhibit any difference in growth of CFU-GM or BFU-E as compared with mock exposed bone marrow cells. HIV-1 DNA could not be detected by the PCR technique in individual colonies derived from HIV exposed marrow. This study suggests that committed myeloid and erythroid progenitors from AIDS patients are responsive to hematopoietic growth factors in vitro and do not appear to contain HIV-1 DNA. Also, HIV or its envelope gp did not alter the growth of hematopoietic progenitor cells in vitro. No evidence of HIV infection of progenitor cells could be demonstrated. Impaired hematopoiesis in patients with AIDS may not be related to direct effects of HIV on committed progenitor cells.

Acquired Immunodeficiency Syndrome↗

Aflatoxin B1-specific cytochrome P-450 isozyme (P-450-AFB) inducible by 3-methylcholanthrene in golden hamsters.

Hepatic microsomes of polychlorinated biphenyl (PCB)-treated Syrian Golden hamsters possessed a higher potency toward aflatoxin B1 activation, based on the Ames test, than other animal species. This activity was induced in hamsters preferentially by treatment with 3-methylcholanthrene rather than phenobarbital. The contribution of an isozyme of cytochrome P-450 (P-450-AFB) to the activity of hamster livers for aflatoxin B1 was studied. P-450-AFB, purified from 3-methylcholanthrene-treated hamster livers, was shown to possess the highest activation of aflatoxin B1 in the Ames test. The quantification of this isozyme by a fluorometric sandwich enzyme-linked immunosorbent assay (ELISA) demonstrated that P-450-AFB was induced mainly in Syrian Golden hamsters but not in Chinese hamsters, or in other species. This isozyme constitutes approximately 40% of the total cytochrome P-450 of the hepatic microsomes from 3-methylcholanthrene-treated Golden hamsters but only 1% in the microsomes of phenobarbital-treated hamsters. Thus, we conclude that the high activity of Golden hamster livers towards aflatoxin B1 activation was due presumably to this distinct and unique cytochrome P-450 isozyme which was induced mainly by 3-methylcholanthrene in Golden hamsters.

Aflatoxin B1↗

The amino-terminal structures that determine topological orientation of cytochrome P-450 in microsomal membrane.

We previously showed that the amino-terminal region of P-450 is responsible not only for targeting to endoplasmic reticulum (ER) membrane but also for stable anchoring to the membrane. In the present study, we introduced several mutations or deletions into the signal-anchor region of the chimeric proteins in which the amino-terminal regions of two forms of cytochrome P-450 were fused to the mature portion of interleukin 2. The amino-terminal acidic amino acid residues were replaced with basic amino acid residues or the hydrophobic core sequences were partially deleted, and these mutant proteins were assayed in vitro for their capacity to be inserted into or translocated across the ER membrane. The proteins that received the former manipulations were processed and the IL-2 portion was translocated across the membrane. In one case, the processing did not occur, thereby enabling the chimeric protein to anchor on the luminal side of the ER. Those that received the latter manipulation were also processed and the IL-2 portion translocated across the ER. These results strongly suggest that the signal-anchor function is determined both by the amino-terminal charged amino acid residues and by the length of the hydrophobic stretch.

Amino Acid Sequence↗

Reduced tumour growth of the human colonic cancer cell lines COLO-320 and HT-29 in vivo by dietary n-3 lipids.

Seventy-five nude mice received subcutaneous inoculation with 1 X 10(7) cells of the human colonic cancer cell lines COLO-320 or HT-29. Tumour growth was assessed over 4 weeks in animals given one of three iso-caloric diets; standard diet, high saturated fat (20% coconut) diet and high n-3 fat (20% Maxepa fish oil) diet. The n-3 diet produced significant tumour growth reduction compared to the other diets for COLO-320 at 3 to 4 weeks (P less than 0.05 at least) and similarly for HT-29 at 4 weeks (P less than 0.05). Significant incorporation of n-3 fatty acids occurred in red cell membranes, adipose tissue and both neutral lipid and phospholipid fractions of tumour lipids in animals fed Maxepa (P less than 0.01 at least). This was accompanied by reduction of linoleic acid and arachidonic acid in these tissues (P less than 0.01 at least) but was most marked in the metabolically labile phospholipid fraction. There was high mitotic activity in the tumours from all the groups but there was no difference according to diet.

Animals↗

Specific inhibitory effect of dietary eicosapentaenoic acid on N-nitroso-N-methylurea-induced mammary carcinogenesis in female Sprague-Dawley rats.

We have investigated the effects of two qualitatively different types of unsaturated fatty acids on N-nitroso-N-methylurea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats. Semipurified diets containing 4.7% eicosapentaenoic acid (EPA) plus 0.3% linoleic acid or 5% linoleic acid were prepared. Animals maintained on these diets were given an i.v. injection of NMU (50 mg/kg body wt) at 50 days of age and killed 20 weeks later. Both tumor incidence and tumor number per rat were significantly lower in the EPA diet group (60.0% and 2.3 +/- 2.5 versus 93.3% and 5.1 +/- 4.5 respectively) for the 5% linoleic acid diet. Furthermore, the average weight of tumor material (total) per rat was significantly lower in the EPA as compared to linoleic acid diet group (2.9 +/- 4.2 g and 11.4 +/- 12.2 g respectively). Analysis of phospholipid fatty acids in the mammary tumors in the EPA diet group showed a higher proportion of C16:0, C18:2, omega-3 fatty acids C20:5 and C22:6 and a lower proportion of C20:4. Furthermore, mammary tumors in rats fed the EPA diet demonstrated significant reduction in prostaglandins. The results thus suggest that inhibition by EPA of NMU-induced mammary carcinogenesis may be mediated via the modulation of lipid metabolism and associated reduction in prostaglandin synthesis.

Animals↗

Production of cytokines by peripheral blood monocytes/macrophages infected with human immunodeficiency virus type 1 (HIV-1).

The study of monocyte/macrophage functions after human immunodeficiency virus type 1 (HIV-1) infection may help in understanding the pathogenesis of AIDS. The production of four cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF), by peripheral blood monocytes/macrophages was evaluated after in vitro infection with HIV-1. HIV-1 infection of these monocytes/macrophages did not result in release of any of these cytokines. Similarly, treatment of uninfected cells with purified recombinant HIV-1 envelope protein did not result in cytokine production. After stimulation with endotoxin or endotoxin plus interferon-gamma, HIV-1-infected monocytes/macrophages produced amounts of TNF alpha, IL-6, GM-CSF, and IL-1 beta comparable to that of uninfected cells. HIV-1 infection does not appear to induce or alter cytokine production by mononuclear phagocytes, which retain the capacity to produce these cytokines after endotoxin stimulation.

Biological Factors↗

Structural requirements for interruption of protein translocation across rough endoplasmic reticulum membrane.

Co-translational translocation of proteins across the membrane of rough endoplasmic reticulum (ER) is interrupted by particular amino acid sequences, which are functionally termed "stop-transfer sequence." We analyzed the structural requirements for the interruption of the peptide translocation. By the manipulation of the cDNA of interleukin 2 (IL2), which passes through ER membrane co-translationally, the middle portion of the IL2 molecule was replaced with systematically altered hydrophobic segments, leucine, alanine, or leucine/alanine mixed clusters. Furthermore, charged amino acid residues were introduced just downstream of the hydrophobic segments. These modified IL2 peptides were synthesized with wheat germ cell-free system in the presence of rough microsomes and the topology of the peptides in the microsomes was assessed by post-translational digestion with proteinase K. We obtained the following results. (i) Each modified protein was processed to the mature form but the extent of stop-translocation varied widely. The ratio of the stopped to the translocated products increased as the length and hydrophobicity of the inserted segment increased. (ii) Shorter hydrophobic segments than naturally occurring native transmembrane segment promoted stop-translocation. (iii) Proteins with hydrophobic segments followed by positive charges were more efficiently stop-translocated than those having negative charges. (iv) If the hydrophobicity of the segment was sufficiently high, the positive charges after the segment were not essential for stop-translocation. We also suggest that the stop-transfer process includes protein-protein interaction between the hydrophobic segment and translocation channel.

Amino Acid Sequence↗

Identification of the second major allergen of Japanese cedar pollen.

We isolated and characterized the second major allergen (Cry j II) from Japanese cedar pollen. We found that most patients with this pollinosis had IgE antibody to this protein in addition to IgE antibody to Cry j I; however, some sera reacted only with Cry j I or Cry j II. IgE-ELISA inhibition studies revealed that Cry j I and Cry j II had no cross-allergenicity. Cry j II did not react with anti-Cry j I monoclonal antibodies. In SDS-PAGE under a non-reducing condition, Cry j II showed a band at the 37 kDa position, compared with the 45-50 kDa bands of Cry j I. N-terminal amino acid sequence of Cry j II was completely different from that of Cry j I.

Allergens↗

Human urinary erythropoietin: preparation with high potency.

Human urinary erythropoietin has been purified to homogeneity. The seven-step procedure yielded a preparation with a potency of 225,000 U/mg protein. SDS-polyacrylamide gel electrophoretic analysis of the purified hormone revealed a single protein band with a molecular weight of about 35,000 that migrated with the biological activity. As to its stability, the purified hormone retained its activity in the presence of 0.001% Tween 20.

Anemia, Aplastic↗

Subarachnoid hemorrhage and spinal root injury caused by acupuncture needle--case report.

The authors report a case of subarachnoid hemorrhage and spinal root injury caused by an acupuncture needle buried in the posterior neck about 30 years before onset. A 33-year-old female presented with sudden onset of severe occipital headaches. Plain x-ray films of the cervical spine revealed a fine gold needle, about 1.5 cm in length, between the C1 and C2 vertebrae. The needle was piercing the spinal nerve root through the dural vein, and was removed. Postoperatively, the pain exacerbated by neck movement disappeared.

Acupuncture Therapy↗

A retrospective clinical and neuroimmunohistochemical study of rheumatoid arthritic patients with atlanto-axial subluxation.

In a retrospective study of 87 RA patients with radiographically documented anterior atlanto-axial subluxation (AAS) in flexion-extension radiographs, 40 had been studied radiographically before they developed AAS. Of these 40 patients, 34 had had occipitocervical pain already before the subluxation. This shows that pain early in the course of the rheumatoid cervical spine is not caused by or associated with AAS itself. In a separate operatively treated group of 5 patients, ligament neuroanatomy in AAS was more closely studied, using specific heteroantisera to cytoskeletal neurofilaments and various transmitter neuropeptides as neural markers and the highly sensitive avidin-biotin-peroxidase complex (ABC) immunohistochemical staining procedure. These specimens were obtained from the ligamentous structures between the posterior arch of the atlas and the spinous process of C2, corresponding to the C1-C2 interspinal non-inflammatory ligament, during atlanto-axial stabilizing operations. This ligamentous tissue contained, in addition to focal inflammatory cell infiltrates, neurofilament and/or neuropeptide immunoreactive neural elements. This finding may suggest that pain early in anterior AAS could be caused not only by synovitis, for example, but also by local ligamentary involvement leading to irritation of local neural elements. This phenomenon may have contributed to the local occipitocervical pain experienced by 34/40 patients who later developed AAS.

Arthritis, Rheumatoid↗

[Effects of optokinetic stimulation on head movement and body sway of children].

We evaluated the effects of horizontal and vertical optokinetic stimulation on head movement (HM) and body sway (BS) in children and adults, using a Jung type optokinetic stimulator, a strain gauge-platform, and a encephalography. Twenty healthy children aged 7 to 9 years and twenty healthy adults aged 20 to 26 years were instructed to stand with feet close together on the platform with eyes open with and without optokinetic stimulation for 60 seconds. In all subjects, optokinetic stimulation significantly increased the total lengths of HM and BS. In addition, optokinetic stimulation significantly increased the areas of HM and BS in children, but not in adults. Although the ratio of the anteroposterior component to the lateral component in BS was significantly higher in children than in adults, the value of HM was not. Children exhibited a characteristic BS in which the anteroposterior swaying velocity was larger than the lateral swaying velocity. In the anteroposterior component, averaged divisional frequencies of BS were significantly larger in children than in adults. However, averaged divisional frequencies in the lateral component of BS and those in the anteroposterior and lateral components of HM did not differ between the two age groups. The ratio of the total length of HM to that of BS was significantly higher in children than in adults. These results suggest that HM and BS of children are readily affected by optokinetic stimulation, and that in children, the BS velocity in the anteroposterior direction is higher than that in the lateral direction.

Adult↗

[A new counting method for airborne Japanese red cedar and grass pollen allergens by the immunoblotting technique].

We devised a new counting method of pollen allergen particles which improved the fluorescence immunoblotting technique by Schumacher et al (1988). And by which airborne pollen allergens became visible under 10X magnifier or naked eyes. Airborne pollen allergens collected on the Burkard's sampling tape were transferred onto nitrocellulose membrane and were reacted with anti Cry j I rabbit serum or anti Lol p I rabbit serum, and then treated with alkaline phosphatase conjugated F(ab')2 anti rabbit IgG. Finally, bluish purple spots were obtained by staining with BCIP/NBT phosphatase substrate system. This technique does not require any skillful morphological observation, and is more suitable to measure the amounts of airborne pollen allergen for given pollinosis patients because total pollen allergen particles with common antigenicity are measured. In Japanese red cedar pollen counts, we could not count the spots more than 400 grains per 0.16 cm2 of the sample trapping area due to many overlapping spots. In this case, we tried to calculate the value from the ratio of bluish purple coloured area to one pollen area. However, a more suitable method for estimating the content of pollinosis caused airborne allergens may be colorimetric quantitation using densitometry and displaying the value as allergen content.

Allergens↗

Evaluation of countermeasures for reduction of mouse airborne allergens.

Three kinds of countermeasures for reduction of mouse airborne allergens were evaluated with use of an air sampler and immunochemical methods. Mouse cages and the sampler were placed inside a flexible-film isolator, and concentrations of mouse major allergens in the air were measured. The levels of the airborne allergens, prealbumin and albumin, generated by 10 males, were 3,050 and 492 pg/m3, respectively. Those by 10 females were lower, 317 and 270 pg/m3, respectively. When mouse cages were covered with a filter cap, the airborne allergens inside the isolator were decreased by 90%. When corncob was used as bedding in place of wood shavings, the airborne allergens were decreased by 57 and 77%, respectively. Therefore, for reduction of mouse airborne allergens, we recommend using female mice, covering the cages with filter caps, and using corncob bedding.

Air Pollutants, Occupational↗

A new method of screening for vertical atlantoaxial dislocation.

A new method for the screening and grading of vertical atlantoaxial dislocation is described. The Sakaguchi-Kauppi method is based on a pathologic process in the atlantoaxial joints and the grading system gives a reproducible (interobserver coefficient of variation = 0.062) tool for the screening of vertical dislocation and is also applicable to patients for whom earlier radiographs are not available. There were differences between the results obtained using Redlund's method and the new Sakaguchi-Kauppi method (chi 2 = 44.7, p less than 0.001). This difference stems from the variations in the height of the axis in the normal population and results in a sensitivity and specificity of 84.2% and 90%, respectively, for Redlund's method compared to the new method.

Arthritis, Rheumatoid↗

Measurement of antigen-specific mouse IgE by a fluorometric reverse (IgE-capture) ELISA.

A reverse, or IgE-capture, enzyme-linked immunosorbent assay (ELISA) for measuring ovalbumin-specific IgE antibody in the serum of immunized mice has been developed. Microplate wells were first coated with a commercial anti-mouse IgE rat monoclonal antibody, and then incubated with two-fold serial dilutions of test sera with 10% normal mouse serum as diluent for the capturing of only IgE class molecules. Biotinylated ovalbumin and then beta-D-galactosidase-conjugated streptavidin were added and, finally, 4-methylumbelliferyl-beta-D-galactoside was used as the enzyme substrate. The fluorescence intensity of the reaction product (4-methylumbelliferone) was determined on a microplate fluorescence reader. The sensitivity of this assay was equal to that of passive cutaneous anaphylaxis (PCA). In contrast to indirect ELISAs this IgE-capture assay is free from competition by non-IgE antibodies. Furthermore, it requires much less antigen than the PCA assay.

Animals↗