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Biomedical subjects

S Morikawa

Publications and source records attributed to S Morikawa.

At least 109 records · Page 6Linked to original sources

A new monoclonal antibody (IE8) reactive with dendritically shaped cells in the human tonsil.

A new monoclonal antibody (mAb), 1E8 (IgG1, kappa), was obtained from a hybridoma prepared by fusion of mouse myeloma cells (NS-1) with splenic cells of mice immunized with a human B blastic malignant lymphoma cell line, HPE-Ret-3 (Ret-3). The mAb showed a reactivity unrestricted to a specific cell lineage on flow cytometrical analysis of the reactivity with human lympho-hematopoietic cell lines. In peripheral blood, 1E8 reacted with the cells of all lineage, that is, lymphocytes, monocytes, granulocytes and platelets, even though its intensity was very low by immunohistochemistry. Immunohistochemical examination of human tonsil with 1E8 showed a characteristic staining pattern. Positive cells scattered in follicular (mantle zone and germinal center), parafollicular (T-dependent area), subepithelial and interstitial connective tissue areas. These positive cells seemed to be categorized into dendritically shaped cells (DSC), including dendritic cells (DC) and a subpopulation of macrophages in follicles, interdigitating cells (IDC) and irregularly shaped mononuclear cells. The localization of 1E8 antigen staining was similar to that of integrin CD11c, although its distribution on hematopoietic cell lines did not coincide with that of 1E8 antigen. Immunobiochemical studies showed that 1E8 bound two cell surface proteins with molecular size of 70,000-90,000 and 35,000 Da each. Consequently, 1E8 antigen might be a novel marker of DSC.

Animals↗

Evaluation of water molecules in the cold-preserved rat liver by proton magnetic resonance imaging.

Hypothermically preserved rat livers were studied with proton magnetic resonance imaging (1H-MRI) under proton density-, spin-lattice relaxation time-, spin-spin relaxation time- and diffusion-weighted (P-W, T1-W, T2-W and D-W) conditions. Relative signal intensities (RSI) of the liver to distilled water in terms of P-W, T1-W, T2-W and D-W increased time-dependently during 12 h hypothermic (4 degrees C) preservation with saline, while these parameters did not increase during preservation with University of Wisconsin (UW) solution. One-hour Wiggers' hypotensive treatment before the harvesting increased the RSIs of P-W, T2-W and D-W, and the subsequent 12-hour preservation with UW solution did not improve the increased RSIs. These results suggest that 1H-MRI has potential application in evaluating the biophysical changes of water molecules in the liver graft, which were measured by placing the harvested liver in a plastic bag under a magnetic field at a low temperature.

Adenosine↗

Distinct effect of G-CSF on the growth and differentiation of myeloid progenitor cells from chronic idiopathic neutropenia.

Chronic idiopathic neutropenia (CIN) is a disorder characterized by severe neutropenia and a maturational arrest of the neutrophil precursors in the bone marrow. We examined the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the growth and maturation of the myeloid progenitor cells from a patient with CIN. The patient's marrow cells showed poor colony forming activity, but a normal differentiating capacity to the stimulation with rhG-CSF, although they displayed a normal colony forming capacity in the presence of GM-CSF. Our observation indicates the distinct effect of rhG-CSF on the growth and maturation of the myeloid progenitors from a CIN patient.

Aged↗

A role for ferritin in hematopoiesis and the immune system.

Elevated serum ferritin levels have been reported in a number of pathological states. These observations indicate that cells of the immune system can participate in the prevention of potential tissue toxicity from iron accumulation, and iron and iron-binding protein have important effects on immune systems. Ferritin is generally regarded as an intracellular iron storage protein. However, small amounts of ferritin circulate in the serum of normal individuals, and the physiological role of serum ferritin remains obscure. Although the function of ferritin is inevitably linked to iron metabolism, a role for ferritin in hematopoiesis and the immune system has drawn attention for years. Ferritin has an inhibitory effect on the in vitro growth of human hematopoietic progenitor cells and on the proliferation of T lymphocytes in vitro. Recently we report that ferritin may directly suppress the differentiation of human B lymphocytes maturing into antibody producing cells in vitro. In the present review, we summarise this field of research.

B-Lymphocytes↗

Hantavirus infection among Rattus norvegicus in Japan.

Seroepizootiological study of hantavirus infection among 393 urban rats (Rattus norvegicus) captured in six regions in Japan during the period from 1990 to 1994 was carried out by the indirect fluorescent antibody (IFA) test and Western blot (WB). Fifteen out of 393 (3.8%) rat sera were antibody-positive by IFA, i.e., Tokyo Port (12.8%, 6/47), Shimizu Port (5.7%, 2/35), Otaru Port (1.5%, 1/65) and Nagoya City (3.6%, 6/167). In two other regions, i.e., Kasai Seaside Park and Haneda Airport, rat sera were antibody-negative. One serum with a lower IFA titer, 1:64, from Otaru Port was confirmed to be antibody-positive by WB, while two sera from Shimizu Port (IFA titer, 1:32 and 1:64) were not. In Nagoya City, one out of four sera (IFA titer, 1:32) and one of two sera (IFA titer, 1:64) were also confirmed to be antibody-positive by WB. Continuous hantavirus infection among rats in Tokyo Port, Shimizu Port and Nagoya City and the existence of hantavirus among rats in Otaru Port were demonstrated.

Animals↗

[Neonatal EEG findings soon after birth in the intrauterine growth retarded infant].

We performed electroencephalograms in 32 neonates of intrauterine growth retardation (IUGR) within seven days of birth. EEG findings were compared with those observed in neonatal brain damage. Seven EEGs had a dysmature pattern which is seen in the subacute and chronic stages of prolonged and mild neonatal brain depression, and five had a disorganized pattern which is seen in the subacute and chronic stages of severe neonatal brain depression. The other EEGs had a normal neonatal pattern. Seven neonates who had a dysmature pattern were severe IUGR (< or = 2.5 SD). Their head circumference was retarded at birth, and the S/D ratio of the umbilical artery increased, suggesting chronic brain damage in utero. On the other hand, five neonates displaying a disorganized pattern were preterm IUGR (< 37 weeks). They had NST abnormalities. The abnormal EEG pattern observed in IUGR was similar to that observed in postnatally injured neonates. The abnormalities in EEGs are correlated with the degree of later neurological sequelae. The present study suggested that the EEG of IUGR recorded immediately after birth was useful in evaluating their intrauterine environments and postnatal neurological outcome.

Brain Diseases↗

Central cord syndrome secondary to hyperflexion injury of the cervical spine in a child.

A 10-year-old girl sustained hyperflexion injury to the midcervical spine, i.e., wedge compression fractures of the C3, C4, and C5 vertebral bodies, when hit by an automobile, subsequently manifesting central cord syndrome below the C4 spinal cord level. Serial magnetic resonance imaging helped identify the spinal cord lesion at the corresponding levels. Conservative management combined with corticosteroid administration resulted in nearly full neurologic recovery approximately 3 months after the trauma, although a cystic lesion remained present within the spinal cord 11 months after trauma.

Cervical Vertebrae↗

Conformational changes of purine repressor DNA-binding domain upon complexation with DNA.

The purine repressor (PurR) consists of two functional domains: an N-terminal DNA-binding domain and a C-terminal corepressor-binding domain. Recently, the structure of PurR-corepressor-operator ternary complex was determined by X-ray crystallography. In the complex the DNA-binding domain, consisting of 56 amino acids, was composed of four helices. Here, we have determined the solution structure of the DNA-binding domain in its DNA free state by NMR. It consists of three helices and the fourth helix (the hinge helix) region is diordered. The architecture of the first three helices of its DNA free state is very similar to that of its DNA-bound form. The hinge helix is induced by the specific DNA binding and by the dimerization of PurR which is provided by the corepressor-binding domain.

Bacterial Proteins↗

Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices.

The DNA-binding region of Myb consists of three imperfect tandem repeats (R1, R2, and R3). We have determined the solution structure of a specific DNA complex of the minimum DNA-binding domain (R2R3) by heteronuclear multidimensional NMR. Both R2 and R3 contain three helices, and the third helix in each is found to be a recognition helix. R2 and R3 are closely packed in the major groove, so that the two recognition helices contact each other directly to bind to the specific base sequence, AACNG cooperatively; this is a significant arrangement of recognition helices. The three key base pairs in this sequence are specifically recognized by Asn-183 (R3), Lys-182 (R3), and Lys-128 (R2). In contrast, R1 has no specific interactions with DNA from our NMR study of the DNA complex of the full DNA-binding domain (R1R2R3).

Amino Acid Sequence↗

Molecular and biological characterization of fusion regulatory proteins (FRPs): anti-FRP mAbs induced HIV-mediated cell fusion via an integrin system.

Anti-FRP mAbs induced polykaryocyte formation of U2ME-7 cells (CD4+U937 cells transfected with the HIV gp160 gene). Anti-FRP-1 mAb immunoprecipitated gp80-85, gp120 and homodimers of these peptides, and anti-FRP-2 mAb reacted with gp135 identically to the alpha 3 subunit of integrin. Both anti-FRP-1 and anti-FRP-2 mAb-induced cell fusion was blocked by anti-beta 1 integrin antibody, fibronectin or inhibiting anti-FRP-1 antibody. Therefore, anti-FRP mAbs were thought to induce the fusion via an integrin system(s). FRP-mediated fusion was temperature, cytoskeleton, energy and Ca2+ dependent. These experiments showed a possible regulatory function of cell fusion by an integrin system(s).

Amino Acid Sequence↗

H- and L-rich ferritins suppress antibody production, but not proliferation, of human B lymphocytes in vitro.

The effect of human spleen(L-rich) and heart(H-rich) ferritins on the proliferation and differentiation of human B lymphocytes was studied in comparison with that of holo- and apo-transferrins. Ferritins rich in H and L chain, as well as the transferrins, did not inhibit the proliferative response of resting and activated B cells stimulated with polyclonal B-cell mitogen, Staphylococcus aureus Cowan strain I. In contrast, the ferritins, but not the transferrins, clearly suppressed the antibody production by B blasts in T-cell-independent as well as T-cell-dependent system. Kinetic study showed that inhibitory action of ferritins on immunoglobulin (Ig) production was caused at an early stage of B-cell differentiation. The cytoplasmic Ig-containing cells decreased in proportion to the reduction of Ig secretion. The evidence that ferritin inhibited Ig synthesis of Epstein-Barr virus-transformed human B-lymphoblastoid cell line also supported the idea that the effect of ferritin was directed toward the antibody-producing B lymphocytes. The molecular analysis showed that the inhibitory effect of ferritin was regulated at the transcriptional level of the Ig generation signal. Our results suggest that H- and L-rich ferritins exert their inhibitory action on the differentiation of B cells maturing into Ig-producing cells.

Antibody Formation↗

Fingertip replantation: pre-osteosynthesis vein graft technique.

Since 1985 we have been performing replantation of amputated fingertips using a pre-osteosynthesis vein graft technique. First, we locate an artery and vein at the distal part of the fingertip and perform a vein graft. After this, we perform osteosynthesis. Since there is sufficient vessel length, the anastomosis technique becomes easier than with the method previously used. In our department, between 1985 and 1990 we performed 11 Zone I replantations. Ten fingers survived and one failed. There were good results in seven cases and three had fair results. The pre-osteosynthesis vein graft technique is a reliable technique for amputated fingertip replantation.

Adolescent↗

Imaging of phosphoenergetic state and intracellular pH in human calf muscles after exercise by 31P NMR spectroscopy.

Phosphoenergetic and pH images in human calf muscles before and after ischemic exercise were generated by 31P NMR chemical shift imaging (CSI) with a 1.5 T standard clinical MR machine using a home-built volume coil. Acquisition of data was repeated four times with 8 x 8 phase-encoding steps and 1 s repetition time. The total acquisition time was 4 min 16 s. After 3-dimensional (3D) Fourier transformation with zero-filling, 2-dimensional (2D) images with 32 x 32 matrices of phosphocreatine (PCr), inorganic phosphate (Pi), PCr/(PCr + Pi) and pH were constructed. These metabolic images were overlaid with concurrently observed 1H MRI to locate the areas showing metabolic response. After 3 min exercise consisting of repeated plantarflexion of the foot under ischemic conditions, decreases in phosphoenergetic levels and acidosis were the most severe in the peroneus muscles, moderate in the tibialis anterior muscle, and slight in the triceps muscle of the calf. Under maintained ischemic conditions, phosphoenergetic level further decreased, but the acidosis in each muscle did not progress further. Heterogeneous metabolic and pH changes throughout the entire calf muscle were clearly demonstrated in detail by these images.

Acidosis↗

Lactate and pH mapping in calf muscles of rats during ischemia/reperfusion assessed by in vivo proton and phosphorus magnetic resonance chemical shift imaging.

RATIONALE AND OBJECTIVES: Metabolic images of phosphocreatine, inorganic phosphate (Pi), and pH formed by phosphorus 31 (31P) nuclear magnetic resonance (NMR) spectroscopy, that of lactate by proton (1H) NMR spectroscopy and 1H magnetic resonance imaging (MRI) were concurrently observed using the same ischemia/reperfusion model in the calf muscles of rats. From the multidimensional analyses, the correlation between tissue pH and lactate formation was examined. METHODS: Six rats were used in the study. For the selective detection of lactate by 1H NMR, a multiple quantum coherence filter was used. The localization of the metabolites and pH was achieved by three-dimensional chemical shift imaging technique. These observations were repeated in 1-hour cycles during 6 hours of ischemia and after reperfusion. RESULTS: The tibialis anterior and gastrocnemius muscles, which are mainly composed of fast-twitch muscle fibers, showed severe tissue edema and irreversible phosphoenergetic change. These muscles became more acidic than other portions of the calf. In contrast, the central part of the calf including soleus muscle (slow-twitch muscle) showed reversible phosphoenergetic changes. Lactate accumulated mainly between the muscles showing reversible and irreversible phospho-energetic changes. CONCLUSION: Discrepancy between acidosis and lactate accumulation in calf muscles was observed in this ischemia/reperfusion model, although the exact reasons for this phenomenon could not be explained by this study.

Animals↗

Immunosuppressive activity of bromocriptine on human T lymphocyte function in vitro.

Bromocriptine (BRC), a dopamine type 2 agonist, prevents secretion of pituitary prolactin (PRL). BRC has been shown to impair lymphocyte responsiveness toward antigenic stimulation by decreasing serum PRL levels. Hypoprolactinaemia induced by BRC produces a similar immunosuppressive effect, as observed in hypophysectomized rats, which is restored by the administration of PRL. Therefore, the immunosuppression induced by BRC has been interpreted as the result of hypoprolactinaemia. However, the direct mechanism of BRC in immune response has never been evoked. We recently reported that BRC has an immunosuppressive activity on human B lymphocyte function in vitro. In the present study we demonstrate that BRC suppresses T cell proliferation by means of blocking IL-2 production by T cells as well as mixed lymphocyte reaction (MLR) in a dose-dependent manner. We could not detect the immunoreactive PRL activity in the conditioned medium from polyclonal T cell mitogen-stimulated T cell cultures. Then, the immunosuppressive activity of BRC on human T cell function appeared to be independent of its hypoprolactinaemic effect. Treatment with low-dose cyclosporin A (CsA) or FK506 in combination with BRC has proved more effective than either drug alone in suppression of T cell proliferation and CD25 antigen expression. Thus, the therapeutic application of BRC in combination with immunosuppressants may enhance the immunosuppressive effect, while at the same time decreasing the toxicity.

Bromocriptine↗

An autopsy case of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia.

A case of acquired immunodeficiency syndrome (AIDS) with preceding aplastic anemia is reported. The patient was a 36 year old female who had been diagnosed as having aplastic anemia 10 years before and thereafter had received multiple transfusions. Human immunodeficiency virus (HIV)-seropositivity was revealed 10 months prior to her death, but no particular clinical signs indicating HIV infection, pre-AIDS or onset of AIDS were recognized before serological diagnosis, although the slow progression of leukopenia was noted along with thrombocytopenia. Her general condition deteriorated during the last 10 months accompanied by an acute decrease in the CD4/CD8 ratio. Autopsy revealed full-blown AIDS: systemic aspergillosis, progressive multifocal leukoencephalopathy, Epstein-Barr virus-related B cell lymphoma arising in the diaphragm and severe lymphocyte depletion in the lymph nodes and spleen. Markedly hypoplastic bone marrow was considered to be primarily attributable to the aplastic anemia but the affection of AIDS was not excluded. The possible transmission route of HIV and the effect of the preceding aplastic anemia on the infection and clinical course of AIDS are discussed.

AIDS-Related Opportunistic Infections↗

Immunoelectron microscopic localization of carcinoembryonic antigen in gastric adenocarcinoma cell lines.

The distribution of carcinoembryonic antigen (CEA) in human gastric adenocarcinoma cell lines (HPE-GAC-3 cells and HPE-GAC-2 cells) was determined immunohistochemically by indirect peroxidase-labeled antibody method at the light and electron microscopic levels. In GAC-3 cells that proliferated as non-adherent single cells, CEA was located in the perinuclear spaces, the endoplasmic reticulum, Golgi apparatus, vesicles, multivesicular body (MVB) and entire plasma membrane. Membrane CEA was shown to be internalized into MVB in GAC-3 cells. In GAC-2 cells that form an acinus, CEA was predominantly present along the microvilli of the luminal surface and in glycocalyceal bodies, the vesicles which bud from the microvilli into the lumen. These results suggest that in poorly differentiated cancer cells CEA is transported over the entire cell surface, retained on the membrane and accumulated into the cell by way of the MVB, but in well differentiated cancer cells the newly synthesized CEA is rapidly and predominantly transported to the luminal surface and rapidly released from the membrane into the lumen by way of the glycocalyceal body.

Adenocarcinoma↗