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Biomedical subjects

Y Maeda

Publications and source records attributed to Y Maeda.

At least 685 records · Page 38Linked to original sources

Induction of demyelination by intraneural injection of antibodies against sulfoglucuronyl paragloboside.

Sulfoglucuronyl glycolipids (SGGLs) carry the glucuronyl 3-sulfate (HNK-1) epitope which is recognized by monoclonal IgM paraproteins from patients with demyelinating polyneuropathy. We report that intraneural injections of rat anti-SGGL antibodies induce demyelination in rat sciatic nerve, along with mild to moderate clinical symptoms. Morphologically, vesiculation and loosening of the myelin sheath were observed 3 h postinjection, followed by extensive demyelination and macrophage infiltration after 4 days. Since the anti-SGGL antibodies showed no cross-reactivity with other components in rat sciatic nerve, these results indicate that SGGLs alone can serve as the target antigens in demyelinating neuropathy.

Animals↗

Dynamic X-ray diffraction measurements following photolytic relaxation and activation of skinned rabbit psoas fibres.

1) The ATP binding and crossbridge dissociation in muscle fibres is as fast as in solution, has a Q10 ca. 2-3, and is not measurably strain sensitive. 2) The final ADP release from the AM.ADP state achieved by adding ADP to rigor fibres must be greater than or equal to 69 sec-1 at 10 degrees C, and the combination of this rate and the ADP rebinding rate at 1 mM ADP limits the ATP induced crossbridge dissociation rate at greater than 2 mM ATP, but these kinetics were not strain sensitive. The strain sensitive steps must occur earlier on the attached pathway. 3) On activation, the equatorial changes thought to reflect crossbridge attachment are faster than tension production. The 10 intensity may change slightly ahead of the 11. This rate was not very temperature sensitive unlike the tension producing step in the mechanism. 4) The re-equilibration of equatorial intensity levels was much faster on activation from the rigor state than from the relaxed state. We conclude that crossbridges do not necessarily move far from the thin filaments when they detach in a fully activated thin filament system. 5) The 14.3 nm meridional intensity increases greater than 200% on fibre activation at 24 degrees C. The structural reorganisation of the heads responsible for this increase is associated with the tension generating step in the ATPase mechanism rather than the initial binding of bridges.

Adenosine Diphosphate↗

X-ray diffraction studies on muscle regulation.

Using the intensity of the outer part of the second actin layer line as an indicator of thin filament conformation in vertebrate muscle we were able to identify the four different states of rest, and the three states induced by the presence of Ca2+ ions, rigor bridge attachment and actively cycling bridges, respectively. These findings are in qualitative agreement with a number of biochemical studies by Eisenberg and Greene and others, indicating that activation of the thin filament depends both on Ca2+ ions and crossbridge binding. Yet quantitatively, the biochemical data and our structural data are contradictory. Whereas the biochemical studies suggest a strong coupling between structural changes of the thin filament and the ATPase activity, the structural studies indicate that this is not necessarily the case. Troponin molecules also change their conformation upon activation depending on both Ca2+ ions and crossbridge binding as demonstrated by the early part of the time course of the thin filament meridional reflections in contracting frog muscle. Low ionic strength which has been shown by Brenner and collaborators to increase weakly binding crossbridges in relaxed rabbit psoas muscle does not influence the intensity of the second actin layer line in this muscle. Yet in contracting frog muscle the increase of the second actin layer line increases very rapidly in one step, suggesting that weak binding bridges which are attached to actin prior to force production may indeed influence the thin filament conformation. It therefore appears that weakly bound bridges in the low ionic strength state do not have the same effect on the thin filament conformation as weakly bound bridges in an actively contracting muscle. Arthropod muscles like the thin filament regulated lobster muscles differ from vertebrate muscle in not showing an increase of the second layer line during contraction, which may have to do with differences in crossbridge attachment. The myosin-regulated molluscan muscle ABRM shows a large increase on the second actin layer line upon phasic contraction and a much smaller increase in catch or rigor, indicating that actively cycling bridges influence the thin filament conformation differently than catch or rigor bridges. Several pieces of evidence which we have briefly outlined in this paper suggest that the thin filament conformational changes we have observed do not arise solely from tropomyosin movements and that conformational changes of actin domains should be considered.

Animals↗

Effects of subarachnoid hemorrhage and a thromboxane A2 synthetase inhibitor on intracranial prostaglandins.

The effects of subarachnoid hemorrhage (SAH) on intracranial prostaglandins (PGs) were studied in canines. Subarachnoid hemorrhage was produced by the "two hemorrhage" method. Basilar artery caliber and regional cerebral blood flow (rCBF) in the occipital cortex were reduced by 42% and 43% during delayed vasospasm, respectively. Once delayed vasospasm had developed, intravenous infusion of OKY-046, a selective inhibitor of thromboxane (TX) A2 synthetase, induced no significant change in angiographic vasospasm but caused a significant increase in rCBF. In delayed vasospasm, cortical levels of PGF2 alpha were significantly decreased, whereas plasma levels of PGF2 alpha and TXB2 in the transverse sinus were significantly increased. The intravenous infusion of OKY-046 in delayed vasospasm induced a significant increase in cortical PGF2 alpha and PGE in the occipital cortex, and caused a significant increase in plasma 6-keto-PGF1 alpha and a significant decrease in plasma TXB2 in the transverse sinus. In delayed vasospasm, decreased cortical levels of PGF2 alpha may reflect a decrease in rCBF and increased plasma PGF2 alpha and TXB2 levels may reflect enhancement of intravascular coagulation. These PGs have very strong and various biological activities. The results suggest that SAH induces complicated changes of intracranial PGs and OKY-046 can improve these pathological changes.

Animals↗

Induction of anti-idiotypic T cells through a network mechanism.

BALB/c mouse T cells that recognized the idiotype expressed on M104E(mu, lambda 1) were induced by immunization with Dextran B-1355. T cells derived from mice immunized with 1 mg of Dextran B-1355 showed a marked proliferative response against M104E, whereas T cells from mice immunized with Ficoll or smaller amounts of Dextran B-1355 did not. BCL1Id, which had an identical isotype, did not induce proliferation of T cells. The T cell proliferative response against the idiotype on M104E required macrophages as antigen-presenting cells. The proliferative response was inhibited when antigen-presenting cells were treated with NH4Cl or chloroquine, which are antigen-processing inhibitors. These results indicate that anti-idiotypic T cells which recognized processed idiotopes could be induced physiologically through a network mechanism.

Animals↗

Time-resolved changes in equatorial x-ray diffraction and stiffness during rise of tetanic tension in intact length-clamped single muscle fibers.

We report the first time-resolved x-ray diffraction studies on tetanized intact single muscle fibers of the frog. The 10, 11, 20, 21, 30, and Z equatorial reflections were clearly resolved in the relaxed fiber. The preparation readily withstood 100 1-s duration (0.4-s beam exposure) tetani at 4 degrees C (less than 4% decline of force and no deterioration in the 10, 11 equatorial intensity ratio at rest or during activation). Equatorial intensity changes (10 and 11) and fiber stiffness led tension (t1/2 lead 20 ms at 4 degrees C) during the tetanus rise and lagged during the isometric phase of relaxation. These findings support the existence of a low force cross-bridge state during the rise of tetanic tension and isometric relaxation that is not evident at the tetanus plateau. In "fixed end" tetani lattice expansion occurred with a time course similar to stiffness during the tetanus rise. During relaxation, lattice spacing increased slightly, while the sarcomere length remained isometric, but underwent large changes after the "shoulder" of tension. Under length clamp control, lattice expansion during the tetanus rise was reduced or abolished, and compression (2%) of the lattice was observed. A lattice compression is predicted by certain cross-bridge models of force generation (Schoenberg, M. 1980. Biophys. J. 30:51-68; Schoenberg, M. 1980. Biophys. J. 30:69-78).

Animals↗

The late waves of brainstem auditory evoked potentials in children with cerebrovascular diseases.

We examined brainstem auditory evoked potentials (BAEPs) in 28 children with cerebrovascular diseases and 38 normal control subjects and investigated the neuroanatomic correlations of the late waves (VI and VII) of the BAEPs. The patients included 19 patients with moyamoya disease and 9 with other cerebrovascular accidents. Wave VI was more consistently seen (only missing in 2 cases, 5%-2 ears, 3%) than wave VII (missing in 26 cases, 68%-40 ears, 53%) in the control group. Absent, depressed or prolonged wave VI correlated well with cerebral lesions involving internal capsule and basal ganglia, while wave VII had a less significant correlation with any cerebral lesions in children with cerebrovascular diseases.

Adolescent↗

Coexistence of fusion receptors for human T-cell leukemia virus type-I (HTLV-I) and human immunodeficiency virus type-1 (HIV-1) on MOLT-4 cells.

Human immunodeficiency virus type-1 (HIV-1) and human T-cell leukemia virus type-I (HTLV-I) have a similar tropism for target cell types, especially for CD4+ T cells. In this study, we provide evidence that receptors of these two viruses exist independently on the target cell. We established an HTLV-I-producing CD8+ T cell line (ILT-8M2) with a remarkable cell fusion capacity. When cocultured with MOLT-4 cells, ILT-8M2 cells induced giant syncytia more efficiently than any other tested HTLV-I-producer cell lines. In contrast to other HTLV-I-producers, ILT-8M2 cells were minimally susceptible to cytopathic effects of HIV-1 due to very low expression of CD4, although they were able to be persistently infected by HIV-1. The indicator MOLT-4 cells are known to respond well to HIV-1-induced cell fusion, but they lose this ability if they become persistently infected with HIV-1 because of the reduction of CD4 receptor expression. ILT-8M2 was, however, still capable of inducing syncytia with the MOLT-4 cells persistently infected by HIV-1 (MOLT-4/IIIB). This syncytium formation was dependent on the HTLV-I-envelope, as it was inhibited by HTLV-I-positive human sera or a monoclonal antibody to HTLV-I gp46 but not by monoclonal antibodies to HIV-1 gp120 or CD4. Moreover, ILT-8M2 cells persistently infected by HIV-1 (ILT-8M2/IIIB) induced both HTLV-I- and HIV-1-mediated syncytia with uninfected MOLT-4 cells. These results suggest that HTLV-I induces cell fusion utilizing receptors on the target cells independent of HIV-1-receptors.

CD8 Antigens↗

A case of epilepsy characterized by spike-wave stupor followed for long period.

A 34-year-old housewife with nonconvulsive status epilepticus was followed up for 20 years since the initial fit. She maintained some contact with reality during the stupor and recalled the episode to some extent, while the EEG showed continuous spike-wave complexes. During the clinical course, the main type of seizures was spike-wave stupor, of which the maximum frequency was several times a week in the hospital and the duration was many minutes to several hours, and also secondarily generalized convulsive seizures occurred approximately once a month. The lasting control of spike-wave stupor was not achieved in spite of the various medications for the long follow-up period. The ictal EEGs of spike-wave stupor always showed the frontal origin. The meaning of the term "nonconvulsive status epilepticus" in this case was briefly discussed.

Adult↗

Neuropathology of the central nervous system in acquired immune deficiency syndrome (AIDS) in Japan. With special reference to human immunodeficiency virus-induced encephalomyelopathies.

The neuropathological features of the central nervous system in 15 autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono- and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.

AIDS Dementia Complex↗

Malignant lymphomas in Japanese AIDS patients.

Seven non-Hodgkin's malignant lymphomas (MLs) were found in 25 Japanese AIDS (acquired immune deficiency syndrome) patients who died at two hospitals in Tokyo. All of these MLs originated from extranodal organs including the brain (three cases), skin (two cases) liver and adrenal gland. B cell markers were demonstrated in all of them. Epstein-Barr virus (EBV) capsid antigen (EBVCA) was demonstrated in 5/7, nuclear antigen (EBNA) in 2/2, the W fragment of EBV DNA by in situ hybridization in 5/7 and the same fragment by PCR in 6/7, indicating high association of these MLs with EBV. The adult T cell leukemia/lymphoma (ATL), endemic in south-west Japan and known to have a high association with HTLV-I, was not found in this series. The incidence of ML among the present AIDS cases is higher than in any other autopsy reports from western countries, although statistical analysis did not show this to be significant in comparison to some of these reports at a level of p less than 0.05. In spite of apparent higher incidence, the histopathologic and immunophenotypic characteristics of AIDS-associated MLs in Japan are in accordance with those in western countries.

Acquired Immunodeficiency Syndrome↗

[Cryptosporidium diarrhea developing in two Japanese adults--one in AIDS and the other in a normal host. Research Group for Infectious Enteric Diseases, Japan].

Case I: A middle-age homosexual male developed AIDS with Pneumocystis carinii pneumonia (PCP) and esophageal candidiasis in 1986 during his stay in an European country about five months prior to transfer to Tokyo Metropolitan Komagome Hospital, Tokyo, in 1987. He was also diagnosed as having cryptosporidiosis presenting with mild diarrhea a month following the diagnosis of PCP. Diarrhea was successfully treated with spiramycin. On transfer to Tokyo Metropolitan Komagome Hospital, he was febrile but had no diarrhea. Serum HIV and TPHA were positive and his blood lymphocyte subset T4a was markedly decreased. On the 13th day after transfer to the hospital, watery diarrhea appeared. Cryptosporidium oocysts were detected from the feces taken on the 17th hospital day. The patient died of Escherichia coli septicemia on the 38th hospital day. Autopsy finding yielded Cryptosporidium infection widely spread over the stomach, ileum, bile and pancreatic ducts. Case II: A 31-year-old previously healthy female presented with abrupt onset of mucous stool five times daily. Mucous passage continued on the subsequent days despite administration of loperamide, and the passage increased to 20 times daily with mucous to watery diarrhea associated with mild abdominal cramps and nausea on the 4th day after onset of illness. On the 6th day of illness, she visited Tokyo Metropolitan Komagome Hospital. She denied close contact with pet animals or contact with any person presenting diarrhea. She had no recent history of travelling anywhere outside Tokyo. On examination she was an apparently healthy woman except for a slightly distended abdomen with localized tenderness in the right upper quadrant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

[A case of Plasmodium vivax malaria with findings of DIC].

We reported a rare case of Plasmodium vivax malaria who showed findings of disseminated intravascular coagulation (DIC). A 50-year-old Japanese male was sent to our hospital with the diagnosis of Plasmodium vivax malaria on the 26th of April, 1990. He had stayed in the Solomon Islands from Oct. 1987 to Dec. 1989, and had febrile episodes during his stay in the island. On April 18, 1990, he complained of a high fever with chills, and showed the same episodes on the 20th, 22th and was diagnosed as malaria. He was treated successfully with the sulfadoxine 500 mg and pyrimethamine 25mg (Fansidar), following the normal temperature on the 4th day and disappearance of malarial parasites in the peripheral blood smear on the 6th day. Interestingly, he had thrombocytopenia and a high titer serum level of fibrin degradation product (FDP) supporting the questionable diagnosis of DIC. Even on the 12th day after improved thrombocytopenia by treatment with Gabexate (FOY), the serum level of FDP, D-dimer and thrombin-nati-thrombin (TAT)III complex still remained at high titer levels. One month later he was readmitted for a relapse of Plasmodium vivax malaria, when he showed thrombocytopenia but the serum level of FDP, D-dimer, TAT III complex and PM.alpha 2 PI complex were normal levels. We concluded that the thrombocytopenia and the high titer of FDP at his first admission was a manifestation of DIC.

Animals↗

Identification and mapping of neutralizing epitopes of human parvovirus B19 by using human antibodies.

We identified and mapped the regions responsible for neutralization in the human parvovirus B19 structural protein by using region-specific human antibodies derived from seropositive blood donors. The region-specific antibodies were purified by using affinity columns coupled with synthetic peptides of the hydrophilic regions including the beta-turn structure deduced by the predicted secondary structure of VP2. Fifteen highly specific antibodies against the synthetic peptides were obtained. Ten of them were able to precipitate the radiolabeled virus. Six of them proved to be able to protect the colony-forming unit erythroid cells in human bone marrow cell cultures from injury by the virus. The sequences recognized by the six neutralizing antibodies were sites corresponding to amino acids 253 to 272, 309 to 330, 325 to 346, 359 to 382, 449 to 468, and 491 to 515 from the amino-terminal portion of VP2. These observations suggest that the neutralizing epitopes were distributed in the region from amino acid 253 in the amino-terminal portion of VP2 to the carboxyl terminus of VP2.

Amino Acid Sequence↗

Identification of the region including the epitope for a monoclonal antibody which can neutralize human parvovirus B19.

In this study, we identified a region in the human parvovirus structural protein which involves the neutralization of the virus by a monoclonal antibody and site-specific synthetic peptides. A newly established monoclonal antibody reacted with both viral capsid proteins VP1 and VP2. The epitope was found in six strains of independently isolated human parvovirus B19. The monoclonal antibody could protect colony-forming unit erythroid in human bone marrow cell culture from injury by the virus. The monoclonal antibody reacted with only 1 of 12 peptides that were synthesized according to a predicted amino acid sequence based on nucleotide sequences of the coding region for the structural protein of B19 virus. The sequence recognized by the antibody was a site corresponding to amino acids 328 to 344 from the amino-terminal portion of VP2. This evidence suggests that the epitope of the viral capsid protein is located on the surface of the virus and may be recognized by virus-neutralizing antibodies.

Amino Acid Sequence↗

Effect of therapy with oxygen under high pressure on regional cerebral blood flow in the interval form of carbon monoxide poisoning: observation from subtraction of technetium-99m HMPAO SPECT brain imaging.

Changes in brain images with single photon emission computed tomography (SPECT) using 99mTc hexamethylpropyleneamine oxime (HMPAO) before and after therapy with oxygen under high pressure (OHP) were measured in a 66-year-old man with the interval form of carbon monoxide (CO) poisoning by a new technique, i.e., subtraction of brain images. This study was performed 187 days after acute CO poisoning, in a state of chronic akinetic mutism that followed a lucid interval. A diffuse, but frontal-dominant, hypoperfusion pattern involving both the gray and white matter was observed in the pre-OHP SPECT image. After OHP, regional cerebral blood flow increased in both the gray and white matter and markedly increased in the frontal cortical regions. The present finding suggests that OHP is effective against the chronic state of the interval form of CO poisoning.

Aged↗

Effects of insulin and myo-inositol on embryo growth and development during early organogenesis in streptozocin-induced diabetic rats.

We have previously shown that myo-inositol depletion in the embryonic tissue at a critical stage of organogenesis has a crucial role in hyperglycemia-induced embryopathy. This study tested whether myo-inositol depletion in early organogenesis contributes to the pathogenesis of streptozocin-induced diabetic embryopathy. Rats were made diabetic by streptozocin administration before conception, and the diabetic rats were treated with diet supplemented by 2% myo-inositol or insulin from 6 to 11 gestational days during the period of maximum teratological susceptibility. In each group on the 11th gestational day, growth retardation and incidence of malformations were recorded, and myo-inositol and sorbitol content in the embryonic and extraembryonic tissues were examined. In diabetic rats, the myo-inositol content of the embryos was decreased by 36% (P less than 0.01) compared with control rats, and there was growth retardation (crown-rump length 3.37 +/- 0.04 vs. 3.87 +/- 0.03 mm, P less than 0.01; somite no. 27.5 +/- 0.2 vs. 29.1 +/- 0.2, P less than 0.01) and a significantly increased incidence of the neural lesions (17.6 vs. 1.9%, P less than 0.01). Insulin treatment resulted in near normalization of maternal serum glucose and complete restoration of myo-inositol content in the embryos with significant improvement of the growth retardation (crown-rump length 3.55 +/- 0.06 vs. 3.37 +/- 0.04 mm, P less than 0.05; somite no. 28.2 +/- 0.13 vs. 27.5 +/- 0.2, P less than 0.05) and a significantly lowered incidence of neural lesions (2.5 vs. 17.6%, P less than 0.01) compared with those of the untreated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Basic studies on ursodeoxycholyl-para-aminobenzoic acid for evaluation of intestinal microflora.

A newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) was investigated to determine its suitability for evaluation of enteric bacteria. This compound, PABA-UDCA, was deconjugated by cholylglycine hydrolase to release free PABA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriologic experiments almost all the microorganisms that split glycocholic acid deconjugated PABA-UDCA. In rat experiments urinary excretions of PABA were measured during 6 h after oral administration of 10 mg PABA-UDCA (PABA-UDCA administration test). Ten control rats excreted 338.5 +/- 13.8 micrograms (mean +/- SE) of PABA; 10 rats with intestinal stagnant loop excreted more (673.6 +/- 70.2 micrograms; P less than 0.01); whereas 10 rats in each of 7 groups pretreated with oral administration of various antibiotics excreted less (P less than 0.001; polymixin B + tinidazole, 14.0 +/- 2.5 micrograms; polymixin B, 224.9 +/- 23.5 micrograms; tinidazole, 42.7 +/- 8.6 micrograms; kanamycin, 50.3 +/- 5.8 micrograms; clindamycin, 57.4 +/- 7.4 micrograms; vancomycin, 70.4 +/- 8.5 micrograms; and paromomycin, 160.4 +/- 16.4 micrograms). This result was reflected by the bacterial mean count of feces. In the PABA-UDCA administration test, after 2 months of feeding with different diets, rats with high-fiber diet (n = 10) excreted less PABA in urine (70.9 +/- 15.9 micrograms; P less than 0.001) than rats on a control diet (n = 10) and a high-protein-high-fat diet (n = 10) (288.9 +/- 34.5 micrograms and 386.7 +/- 61.2 micrograms, respectively). Fecal bacteriologic status was consistently altered. In human volunteers 250 mg PABA-UDCA was tested. Amounts of PABA excreted in urine during 6 h after dosing were 21.11 +/- 2.02 mg in controls (n = 5) and 12.20 +/- 1.01 mg in the group treated with polymixin B plus tinidazole (n = 5; P less than 0.01). No adverse effect was observed. These basic studies indicate that this compound is likely to offer a simple and rapid method for evaluation of the intestinal microorganisms without use of radioisotopes or expensive, special equipment.

4-Aminobenzoic Acid↗