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Biomedical subjects

S Matsuda

Publications and source records attributed to S Matsuda.

At least 523 records · Page 29Linked to original sources

Seronegative virus carriers in the infection of rabbits with human T lymphotropic virus type I.

Six HTLV-I-transformed T cell lines were prepared from PBL of three rabbits each of B/J and Chbb:HM strains, and were inoculated into newborn rabbits of these two strains, and of their F1 hybrid. None of three B/J cell lines induced anti-HTLV-I antibody response in newborn B/J rabbits, whereas all three Chbb:HM cell lines did induce a response in newborn Chbb:HM rabbits. These B/J cell lines however could induce antibody response in adult B/J as well as newborn Chbb:HM rabbits, and a Chbb:HM cell line could induce a response in a newborn B/J rabbit. Similar unresponsiveness was observed in (B/J x Chbb:HM)F1 hybrids neonatally inoculated with B/J cells. Unresponsiveness was abrogated by reinoculation of some but not other cell lines. Viral antigen-positive cell lines harboring HTLV-I provirus genomes were established from such seronegative B/J and F1 rabbits. Simultaneous inoculation of HTLV-I-transformed cells and SPV resulted in the induction of papilloma and antibody against SPV, but not antibody against HTLV-I. The present findings thus reveal that neonatal infection of HTLV-I could result in immunological tolerance to the virus antigens, thereby leading to a persistent infection without antibody induction.

Animals↗

A morphometric analysis of extracellular space in the developing spinal cord of the chick embryo.

The developmental changes in the amount and distribution of the expanded extracellular space (ECS) (i.e. wider than 100 nm) were analyzed in the cervical spinal cord of chick embryos between stage 9 and 29, using electron micrograph montages, which cover one half of the cross-sectional area of the cord. The percentage of the ECS expansion to the whole cross-sectional area of the cord was 11.0% at stage 9, 7.7% at stage 11, 7.8% at stage 15, and 9.7% at stage 17. It decreased markedly to 3.0% at stage 22 and 1.3% at stage 29. The highest percentage at stage 9 may reflect the dynamic structural changes associated with neural groove closure which takes place around this time. The marked decrease after stage 22 is associated with the rapid overall growth of the cord. Until stage 19, the ECS expansions were mostly elongated and arranged radially with respect to the central canal. The ECS became scarce and arranged randomly thereafter. Throughout the stages examined, especially between stages 17 and 19, percentage was higher in the outer half of the cord than in the inner half. The outer glial limiting membrane was not established by stage 29. Between stages 17 and 22, the percentage was higher in the dorsal region than in the ventral region. This appears to be associated with the regional difference in neuronal maturation. The first blood vessels penetrated the ventromedial portion of the cord around stage 22, where the ECS expansions were relatively scarce. The successive rapid decrease in the amount of ECS expansions can be correlated to the development of vascularization.

Animals↗

Nerve fibres with myelinated and unmyelinated portions in dorsal spinal roots.

Series of 312-605 consecutive sections were prepared from apparently normal dorsal spinal roots of lizard (Lacerta muralis). Two axons which showed a segment enveloped by a compact myelin sheath and a segment devoid of myelin were followed in these serial sections. These provided the opportunity of analysing the structural features that an individual axon presents when it is myelinated and when it is devoid of myelin. Some structural features (e.g., axon calibre and microtubule density) were significantly different in the myelinated segment and in the unmyelinated segment. The factors which possibly influence these features are briefly discussed.

Animals↗

Binding of IgA to erythrocytes from patients with IgA nephropathy.

Primate erythrocytes (RBCs) may be involved in the transport and processing of C3b-containing immune complexes (IC). Compared to RBCs from healthy controls, increased amounts of IgA were detectable on RBCs from 7 of 17 patients with IgA nephropathy (IgA NP). There was no difference in the amount of IgG or IgM. The highest amount of RBC-bound IgA corresponded to 6 ng IgA/10(8) cells. The mechanisms involved in the binding of IgA to RBCs were investigated in vitro. Isolated IgA1 or IgA2 did not bind to RCBs from a patient with IgA deficiency. In contrast, incubation of RBCs with a polyethyleneglycol (PEG) precipitate of serum from a patient with IgA NP which contained IgA-IC resulted in IgA1 binding. However, this binding was not inhibited by monoclonal anti-CR1 or by an excess of IgG or IgM. Factor I did not cause release of IgA from RBCs from patients with IgA NP. Heat-aggregated IgA1 also bound to RBCs and this binding was not affected by the presence of complement. We conclude that minute amounts of IgA-IC are bound to RBCs by a complement- and Fc receptor-independent mechanism. The quantity of IgA-IC associated with RBC is so small that it is unlikely to represent an important in vivo route of IgA-IC transport or processing.

Antigen-Antibody Complex↗

Production of granulocyte colony-stimulating factor by acute myelomonocytic leukemia cells.

Two patients with acute myelomonocytic leukemia (AMMoL) were tested to determine whether or not their cells produced granulocyte colony-stimulating factor (G-CSF). Using the NFS-60 bioassay method, relatively high levels of G-CSF were demonstrated in the serum pre-treated with acid-dialysis and in the media conditioned by leukemia cells. Northern blot analysis for G-CSF using cDNA as a probe revealed that G-CSF production was increased at the mRNA level in the cells. No rearrangement at the DNA level, however, was observed by genomic Southern analysis. Our data indicate that the leukemic cells in AMMoL probably have the capacity to synthesize and secrete G-CSF.

Aged↗

Effect of indomethacin, aspirin, and acetaminophen on in vitro antiviral and antiproliferative activities of recombinant human interferon-alpha 2a.

The effects of indomethacin, aspirin, and acetaminophen on the antiviral and antiproliferative activities of recombinant human interferon-alpha 2a (rIFN-alpha 2a) were studied in vitro. None of the drugs inhibited the antiviral activity of rIFN-alpha 2a in human amnion FL cells against vesicular stomatitis virus, or interfered with its antiproliferative activity against acute lymphoblastic leukemia MOLT-4 cells or renal cell carcinoma NC 65 cells. Although, at high concentrations, aspirin (1 mM) or indomethacin (0.1 mM) alone inhibited the cell growth, rIFN-alpha 2a showed clear additive growth inhibition. It was concluded that neither indomethacin, aspirin, nor acetaminophen directly inhibited the antiviral and antiproliferative activities of rIFN-alpha 2a. The possible use of these three drugs to reduce the adverse effects of rIFN-alpha 2a without spoiling its profitable efficacy in clinical practice is suggested.

Acetaminophen↗

Ca2+-binding of S-100 protein in the presence of K+ and Mg2+.

Ca2+-binding of S-100 protein was studied using a Ca2+ electrode at pH 6.80. In the presence of 0.1 M KCl and 10 mM MgCl2 (ionic strength 0.13), Ca2+-binding to S-100 protein occurred in three steps with positive cooperativity. The numbers of bound Ca2+ ions in the three steps were 2, 2, and 4. The Ca2+-binding constants were 6.9 x 10(3) M-1, 2.9 x 10(3) M-1, and 3.7 x 10(2) M-1, respectively. The Ca2+-binding constants of the first and second steps obtained in the presence of 33.3 mM MgCl2 or 0.1 M KCl (ionic strength 0.10) were 1.4 times larger than those described above. This suggests that Mg2+ does not inhibit Ca2+-binding of S-100 protein. The increase of KCl concentration from 0.1 to 0.2 M caused a decrease of the Ca2+-binding constants to ca. 50%.

Animals↗

Suppression of HBsAg production in PLC/PRF/5 human hepatoma cell line by interferons.

Recombinant human interferon alpha 2a as well as natural human interferons alpha and beta significantly suppressed the production of hepatitis B surface antigen by PLC/PRF/5 cells (which have been established from a human primary hepatocellular carcinoma and proven to carry the hepatitis B virus DNA) and inhibited proliferation of these cells in vitro. However, the production of alpha-fetoprotein by PLC/PRF/5 cells was less significantly affected by any of the interferons. These results suggest that these interferons not only suppress cellular proliferation but also selectively inhibit the action of the HBV gene which is persistently present in these cells.

Carcinoma, Hepatocellular↗

Adult T cell leukemia-like disease experimentally induced in rabbits.

An HTLV-I-transformed T cell line, obtained from the peripheral blood of a virus-infected (B/J X Chbb:HM) F1 rabbit, was able to kill syngeneic newborn rabbits within 7 days, when inoculated intraperitoneally at a dose of 1 X 10(8) cells. Inoculation of 1 X 10(7) cells killed or rendered moribund 50% of inoculated animals, while surviving animals exhibited cell-mediated cytotoxic activities against the transformed cells. The peripheral blood leukocyte counts increased in all surviving animals, in association with appearance of abnormal lymphocytes with convoluted or lobulated nuclei. Pathological examination of animals that died one week post-inoculation revealed no tumors in the abdominal cavity, but accumulation of ascites containing abnormal lymphocytes. Histological examination showed leukemic infiltration in the liver, lungs, spleen and mesenteric lymph nodes. The same cell line was also able to kill syngeneic adult rabbits in 8-10 days when inoculated intravenously, but not intraperitoneally, at a dose of 1 X 10(8) cells. Leukemic infiltration was observed in the major organs of these animals. Adult animals which were already virus carriers were resistant to this lethal inoculation. This rabbit ATL-like disease may prove to be useful as an experimental model for acute adult T cell leukemia.

Aging↗

Megakaryocytopoiesis in polycythemia vera: characterization by megakaryocytic progenitors (CFU-Meg) in vitro and quantitation of marrow megakaryocytes.

Megakaryocytopoiesis in polycythemia vera (PV) was characterized by in vitro growth of marrow megakaryocytic progenitors (CFU-Meg) and quantitation of megakaryocyte numbers in marrow biopsy specimens in 14 patients with PV. Megakaryocyte numbers and CFU-Meg numbers in the 14 patients were variable, with values from the control range to markedly increased numbers. Nine of the 14 patients showed spontaneous CFU-Meg growth, and the presence or absence of spontaneous CFU-Meg growth was found to be related to the degree of marrow megakaryocyte increase, i.e., those with spontaneous CFU-Meg had higher megakaryocyte numbers. None of the plasmas from the PV patients contained detectable levels of megakaryocyte colony-stimulating activity (Meg-CSA), assayed using the culture with nonadherent normal marrow cells and tested plasma without phytohemagglutinin-stimulated leukocyte-conditioned medium as an exogenous source of Meg-CSA. Increased megakaryocyte numbers and resultant thrombocytosis in PV are likely based on the abnormal population of CFU-Meg.

Adult↗

Ferrokinetic evaluation of erythropoiesis in patients with myelodysplastic syndromes.

Erythropoietic activity in patients with myelodysplastic syndrome (MDS) was evaluated by ferrokinetic measurements. Since the conventional plasma iron turnover of MDS patients increased with plasma iron levels after multiple blood transfusions, erythron transferrin uptake was chosen as a parameter of erythroid marrow activity. Although a correlation was shown between plasma iron level and plasma iron turnover (r = 0.50, 0.01 less than p less than 0.02), no correlation existed between the plasma iron level and erythron transferrin uptake (r = 0.25, p greater than 0.1). Erythron transferrin uptake, independent of plasma iron, was significantly higher in MDS patients than in normal subjects (110.6 +/- 67.6 and 67.6 +/- 18.8 mumol/l/dl, respectively; 0.01 less than p less than 0.02). An increased erythropoiesis occurring concomitantly with morphologically normal or increased erythroid cellularity was demonstrated in patients with MDS. The measurement of erythron transferrin uptake might be valuable as an accurate expression of erythroid activity in the hyperferremic state.

Erythropoiesis↗

Nonvisual eye position control in a patient with ocular lateropulsion.

For elucidating the nonvisual eye position control system, we studied the accuracy of saccades toward the remembered position (memory-guided saccades) in a patient with ocular lateropulsion having tonic bias of the eye position. Although the saccadic dysmetria caused by ocular lateropulsion was recorded during memory-guided saccades in the same manner as visually guided saccades, the eyes reached precisely the intended position by corrective saccades. The mean latency of corrective saccades was significantly longer than that of corrective saccades observed for visually guided saccades. This long latency of corrective saccades supports the assumption that feedback information of the eye position is a signal generated by orbital afferents rather than a copy of the motor command.

Eye Movements↗

Bone lengthening in rabbits by callus distraction. The role of periosteum and endosteum.

The histology and mechanics of leg lengthening by callus distraction were studied in 27 growing rabbits. Tibial diaphyses were subjected to subperiosteal osteotomy, held in a neutral position for 10 days and then slowly distracted at 0.25 mm/12 hours, using a dynamic external fixator. Radiographs showed that the gap became filled with callus having three distinct zones. Elongation appeared to occur in a central radiolucent zone; this was bounded by two sclerotic zones. Histologically, the radiolucent zone consisted of longitudinally arranged cartilage and fibrous tissue while the sclerotic zones were formed by fine cancellous bone. New bone occasionally contained islands of cartilage, suggesting it had been formed by endochondral ossification. After completion of distraction, the two sclerotic zones fused, shrank and were eventually absorbed, leaving tubular bone with a new cortex. When the periosteum had been removed at the operation, callus formation was markedly disturbed and there was failure of bone lengthening. Scraping of endosteum, in contrast, did not have a pronounced effect. These results suggest that the preservation of periosteum is essential if bone lengthening by callus distraction is to succeed, and that preservation of the periosteum is more important than careful corticotomy.

Animals↗