[Treatment of acute pancreatitis].
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Biomedical subjects
Publications and source records attributed to K Umehara.
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Production of biphenomycin A by Streptomyces griseorubiginosus 43708 was stimulated by a mixed culture with a partner strain, Pseudomonas maltophilia 1928. This stimulatory effect on biphenomycin A accumulation by the mixed culture was caused by the enzyme activity which strain 1928 possessed. It is suggested that in a mixed culture strain 43708 produces a precursor of biphenomycin A in culture broth and that strain 1928 converts the precursor to biphenomycin A.
Differentiation-inducing activity of over 180 extracts of crude drugs and plants was tested using mouse myeloid leukemia cell line (M1). The methanol extracts of clove (Syzygium aromaticum Merrill et Perry, Myrtaceae) showed remarkable induction of differentiation of M1 cells into macrophage-like cells. From the extract, oleanolic acid (1) and crategolic acid (2) were isolated as the active components. We also tested other triterpenes, such as oleananes, ursanes and dammaranes, to investigate the structure-activity relationship. Some triterpene aglycones showed differentiation-inducing activity, but triterpene glycosides showed little activity. Furthermore, the differentiation-inducing activity of these triterpene compounds was tested against human acute promyelocytic leukemia cell line (HL-60).
An investigation was undertaken to study the effects of germfree (GF) status and mild food restriction on life span in GF and specific pathogen-free (SPF) male ICR mice either full-fed (ad libitum) or on a restricted diet of 4.5 grams per day (equivalent to approximately 80% of full-fed intake) from five-week-old. The mean life span of the full-fed SPF and GF mice was 75.9 and 88.9 weeks respectively, while the mean life span of the food-restricted SPF and GF mice was 117.5 and 109.6 weeks, respectively. Mice in both GF and SPF food-restricted groups were characterized by lower body weight and increased survival. These findings suggest that the cessation of growth may be importantly and perhaps causally related to longevity. The GF mice survived longer than the SPF mice, but the combination of GF status with food restriction did not seem to extend life span more than food restriction alone.
The effects of food restriction on immune function was investigated in germfree (GF) and specific pathogen-free (SPF) mice. They were maintained from five weeks of age under either full-fed or food-restricted conditions to 4.5 grams per day (equivalent to approximately 80% of full-fed intake) of a commercial diet. Longest survival rate was attained in food-restricted SPF mice followed by food-restricted GF, full-fed GF, and full-fed SPF animals. Food-restricted GF mice showed shorter survival rate than their SPF counterparts. This result suggests that food restriction may be just as effective as GF status for extending life span. Immune function declined significantly with age in full-fed groups of GF and SPF mice. In both food-restricted GF and SPF mice, mitogenic response to concanavalin A or lipopolysaccharide and antibody response to sheep red blood cells were lower early in life and became higher later in life as compared with full-fed mice. Hence, the maintenance of effective immunological function until old age may be the reason for food-restricted groups to live slightly longer than full-fed groups.
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In mice infected with a lethal dose of murine cytomegalovirus (MCMV) the serum immunoglobulin (Ig) levels and the Ig-bearing cells in the spleen dropped to barely detectable levels 2 days after infection. In mice with acute but non-lethal MCMV infection, the serum IgM was twice and the IgG 32 times that of the uninfected controls by Day 8 of infection; the numbers of spleen cells bearing IgM and the IgG subclasses (IgG1, IgG2a, IgG2b, IgG3) were also greatly increased. In the asymptomatically infected group, serum IgM remained unchanged but the IgG increased to 16 times that of uninfected controls by Day 11 of infection; the numbers of spleen cells bearing IgM and IgG subclasses were also increased, although to a lesser extent than in the acute, non-lethally infected mice. In the latter two groups, serum IgA and IgA-bearing cells in the spleen did not alter significantly. Complement-requiring neutralizing antibodies to MCMV were detected 8 days post infection.
The immunological response of spleen cells was examined during murine cytomegalovirus (MCMV) infection of germfree (GF) mice. GF mice were more susceptible to MCMV infection than specific pathogen-free (SPF) mice. Recovery from the acute phase of MCMV infection was delayed in GF mice as compared to SPF mice. During MCMV infection, the immune response of GF mice, measured in terms of mitogen and of antibody response to sheep erythrocytes, was more markedly depressed and the recovery from the depression was more delayed than in SPF mice. In MCMV-infected mice, natural killer (NK) cell activity was increased by day 1 and 2 post-infection, with similar kinetics in GF and SPF mice, suggesting that NK cells may be exerting the most potent antiviral effect during the early stage of MCMV infection.
The effects of concurrent murine cytomegalovirus (MCMV) and Klebsiella pneumoniae infections were studied in germfree (GF) mice. The mice received sublethal doses, 5 x 10(5) pfu, of MCMV. K. pneumoniae was injected in doses of 40 to 100 cfu, which by itself killed 0-33% of GF mice. When K. pneumoniae was given to GF mice infected with MCMV, the mortality increased up to 100%, with distinct enhancement persisting until day 10 of the MCMV infection. The virus titer in various organs did not change after superinfection with K. pneumoniae, while the viable counts of K. pneumoniae in organs remained remarkably high until death, suggesting the cause of death to be severe generalized infection by the bacteria. When compared to specific pathogen-free (SPF) mice, GF mice were more susceptible to both MCMV and K. pneumoniae infection, had higher titers of the virus for longer periods in various organs, and showed extension in the duration of enhanced mortality by the bacteria. Histopathologically, the spleen and liver were found to be the most severely affected tissues, more so in GF than in SPF mice, with recovery from the changes being slower in the GF animals.
The comparative abilities of various reagents to prime rabbit alveolar macrophages (AM) to produce reactive oxygen intermediates (ROI) in a chemiluminescent (CL) assay were investigated. It was noted that AM from normal rabbits cultured in a serum-free medium for 18 hr exhibited a "spontaneous" priming response following a challenge with phorbol myristate acetate (PMA); however, "spontaneous" priming was not evident when the AM were cultured for only 3 hr. It was further established that pretreatment of normal AM for 3 or 18 hr with MIF/MAF preparations (serum-free), fetal bovine serum (FBS), or bovine serum albumin (BSA) exhibited marked increases in their CL responses following challenge with PMA. When FBS was used in the culture medium, the priming activity of MIF/MAF was masked because of the high CL responses of controls due to the priming effects of FBS. BSA at concentrations approximately equivalent to the amount in FBS also displayed marked priming activity. Bacterial products (lipopolysaccharide and muramyl dipeptide), latex particles, rabbit IgG, PMA, and opsonized as well as nonopsonized zymosan and bacteria (BCG and Staphylococcus epidermidis) were inactive as priming agents. In comparison, AM from BCG-immune rabbits that were primed in vivo yielded a very large CL response when challenged with PMA. Opsonized zymosan and bacteria produced twofold increases in the CL responses in BCG-immune AM compared to nonopsonized preparations. The marked priming effect of serum on AM cultured for even a short period (3 hr) indicates that normal AM undergo marked changes in culture that complicate the interpretation of AM function when AM are cultured in vitro in media containing serum.
The effect of L-fucose on the priming of AM from normal adult rabbits and their subsequent chemiluminescent (CL) responses to phorbol myristate acetate (PMA) was investigated. It was observed that 12.5 mM L-fucose, but not D-fucose, blocked the "spontaneous" priming of normal AM during an 18-hr incubation period in serum-free RPMI 1640 medium by about 40% (P less than 0.01) as detected by their CL responses to a PMA challenge. In addition, the optimal concentration of L-fucose (12.5 mM) blocked MIF/MAF priming during the 3- or 18-hr incubation period by 71 or 93% (P less than 0.05), respectively, as determined by their CL responses following PMA challenge. It is of particular significance that D-fucose was inactive. These results, together with previously published data, indicate that L-fucose (a) blocks priming of AM for an oxidative response, (b) stimulates random migration of AM, and (c) reverses migration inhibition produced by migration inhibition factor.
Three strong alkaloidal monoamine oxidase (MAO) inhibitors, quinine (1), cinchonicinol ([ 1S,3'R,4'R]-3-(3-ethenyl-4-piperidinyl)-1-(4-quinolinyl)-1-propanol) (2) and cinchonaminone ([ 3'R,4'S]-2-[2-(3-ethenyl-4-piperidinyl)-acetyl]-1H-indole-3-ethanol) (3), were isolated from Cinchonae Cortex (Cinchona succirubra Pav., Rubiaceae). The structures of 2 and 3 were elucidated on the bases of spectral data and chemical evidence, and 3 is a new alkaloid. The inhibitory effects on MAO of 1, 2, 3 and related alkaloids were assayed. The type of inhibition by 1 with respect to benzylamine as a substrate was competitive.
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Streptomyces griseoflavus, a bicozamycin-producing wild type strain and its high-producing one derived from it by multiple (greater than 15) mutagenic treatments, were analyzed physiologically and biochemically. The high-producing strain was characterized by: (1) An increased pool size of amino acids including leucine and isoleucine, precursors for bicozamycin synthesis, (2) an earlier and greater accumulation of intracellular ppGpp, (3) a more accentuated decrease in GTP pool size, (4) a higher specific activity of ornithine transcarbamylase which produces citrulline, (5) an increased ability to form aerial mycelium, and (6) an increased resistance to its own antibiotic. We propose that (1), (2) and (4) may be responsible for the high yields of bicozamycin and, possibly, of some other antibiotics produced by Streptomyces sp.
Tooth movement in orthodontic treatment is achieved by a combination of mechanical and physiologic forces acting on the teeth and their supporting structures to effect the biologic changes that cause teeth to move through bone. Traditional orthodontic appliances using wires, springs, and elastic forces inevitably cause some degree of discomfort and pain. In the present study, a new magnetized edgewise bracket was designed. The magnet works to move teeth mesiodistally and is not merely a mechanical force. It is well adapted to the biophysical system of tooth and bone interrelationships. Therefore, it works effectively, gives less discomfort, and produces less stress for the patient. The new magnetic appliance provides a force system that approaches the ideal orthodontic requirements.
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Upon intestinal infection of heterozygous (nu/+) mice with mouse adenovirus, antiviral resistance can be seen in the form of negative-recovery of virus from feces 2-3 wks post infection. On the other hand, in similar infections in BALB/c nude (nu/nu) mice, the antiviral resistance is manifested as negative-recovery of virus from feces at a later stage, i.e., at around 6 wks post infection. This resistance was not accompanied by rises in interferon titer, rises in natural killer (NK) cell activity, nor was the resistance affected by the introduction of anti-asialo GM1 antibody. No distinct loss of resistance was observed upon administration of carrageenan, but the resistance in the group given carrageenan immediately before and after viral challenge seemed to be slightly reduced. In all infected nu/nu mice, neither neutralizing antibody (NT-Ab) nor complement-dependent NT-Ab could be detected by the usual tube method. On the other hand, a complete abolishment of the antiviral resistance was seen following cyclophosphamide administration. For clarification of the antiviral resistance factor in nu/nu mice, the analysis of antibody other than NT-Ab and complement-dependent NT-Ab, and the problem of resolution of antibody titration remain. Furthermore, it has been noted that the serum IgG titer is high in nu/nu mice and that this level is depressed by cyclophosphamide administration. It is believed that this may be in some way involved with the loss of antiviral resistance observed.