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Biomedical subjects

M Sasada

Publications and source records attributed to M Sasada.

At least 55 records · Page 3Linked to original sources

Transient calcium elevation in polymorphonuclear leukocytes triggered by thrombin-activated platelets.

The effect of thrombin-activated platelets and their release products on the intracellular free calcium concentration ([Ca2+]i) of human polymorphonuclear leukocytes (PMNs) was studied by loading PMNs with a fluorescent indicator of calcium, fura-2. [Ca2+]i of PMNs was transiently elevated by thrombin-activated platelets. The supernatant of thrombin-activated platelets also elicited a transient elevation of [Ca2+]i in PMNs. Pretreatment of the supernatant with hexokinase caused a decrease in the transient [Ca2+]i elevation of PMNs, while hexokinase abrogated the [Ca2+]i elevation of PMNs elicited by 80 mumol/l adenosine triphosphate (ATP). Pretreatment of the supernatant with trypsin also decreased the magnitude of the elevation, while trypsin had no effect on the response to ATP. These findings suggest that thrombin-activated platelets induce a transient [Ca2+]i elevation in PMNs by releasing ATP and some trypsin-sensitive factor(s).

Adenosine Triphosphate↗

Probucol pretreatment enhances the chemotaxis of mouse peritoneal macrophages.

To investigate the effects of probucol on macrophage chemotaxis, we preincubated mouse peritoneal macrophages with probucol for 20 hours in vitro and using a modified Boyden chamber system compared their chemotactic responses with those of control macrophages that were preincubated with vehicle. Probucol pretreatment enhanced the macrophage chemotactic responses to zymosan-activated serum, acetylated low density lipoprotein (LDL), and native LDL. Probucol pretreatment also enhanced the basal migration observed when there was no stimulant in the lower chamber of a modified Boyden chamber. The chemoattracting potency of native LDL was weaker than that of zymosan-activated serum in control macrophages; however, both substances became equally potent when the macrophages were preincubated with probucol. The degree of the enhancement to native LDL after probucol preincubation reached fourfold to eightfold. The fashion of the enhanced migration of macrophages to native LDL after preincubation with probucol was predominantly chemotactic rather than chemokinetic. Time-course experiments revealed that it took more than 12 hours of probucol preincubation to show clearly enhanced macrophage chemotaxis to native LDL. Macrophages preincubated with probucol together with cycloheximide showed markedly reduced chemotaxis compared with macrophages preincubated only with probucol. Probucol pretreatment also enhanced macrophage chemotactic responses to high density lipoprotein, oxidized LDL, and lipoprotein-deficient serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Impaired polymorphonuclear leucocyte function in patients undergoing hepatectomy: adenylate energy charge and superoxide anion production in relation to hepatic mitochondrial redox state.

Patients undergoing hepatectomy have an increased susceptibility to infection. We therefore studied the energy metabolism of the polymorphonuclear leucocyte (PMN), focusing on energy charge and function, especially superoxide anion (O2-) generation, in relation to the hepatic mitochondrial redox state. By labelling the PMN adenine nucleotide pool with radioactive adenine and by superoxide dismutase-inhibitable reduction of ferricytochrome c, the energy charge and O2- production was measured in 18 patients with hepatoma (non-cirrhotic, seven; cirrhotic, 11) undergoing hepatectomy. Their arterial ketone body ratios (KBRs), reflecting the hepatic mitochondrial redox potential, were above 0.7 before operation. After surgery, the 18 patients were divided into two groups: group A, KBR greater than 0.7, n = 10; and group B, KBR less than 0.7, n = 8. The energy charge and O2- release in group B decreased significantly from preoperative values (P less than 0.001 and P less than 0.01 respectively) and when compared with group A (P less than 0.05 and P less than 0.01 respectively). These results suggest that impaired hepatic energy metabolism (KBR less than 0.7) in hepatectomized patients leads to impaired energy charge and O2- production in the PMNs.

Adenine Nucleotides↗

[Follow-up study on anti-HBs levels in vaccines after two and three doses of HB vaccine (1)].

UNLABELLED: An HB prophylaxis vaccination that included a primary and secondary vaccination was carried out on persons working at this university hospital. In the primary vaccination, the subjects were inoculated the second time with a vaccine derived from human blood plasma obtained from the Kitazato Therapeutic Research Institute. The third time, they were inoculated with a vaccine from the Chemo-Sero Therapeutic Research Institute derived from a second-generation vaccine organized ferment. The vaccine used for the second inoculation was obtained from the Chemo-Sero Therapeutic Research Institute. RESULTS: A total of 254 subjects were inoculated with the HB prophylaxis vaccination. 1. Of the 216 subjects inoculated with the primary vaccination, at the time of the second inoculation, 65 subjects (30%) tested positive for antibodies 3-4 months following inoculation. There was an especially high rate among females between 20 and 50 years. Thirty-two subjects (15%) tested positive 15-16 months following inoculation with a high rate among females. 2. Among 132 subjects inoculated the third time with the primary vaccination (those who tested negative in the second inoculation of the above vaccine), 76 subjects (58%) tested positive for antibodies 8-9 months following inoculation with a generally high rate among females. Thirty-five subjects (27%) tested positive 15-16 months after inoculation with a high rate among females between 20 and 30 years and among males between 40 and 60 years. 3. Among the 38 subjects who were inoculated the second time with the secondary vaccination, 8 subjects (21%) tested positive for antibodies 5 months following inoculation, with a high rate among females in their 20's.

Adult↗

[Follow-up study on anti-HBs levels in vaccinees after two and three doses of HB vaccine. (2)].

An HB prophylaxis vaccination that included a primary and secondary vaccination was carried out on persons working at the university hospital. In the primary vaccination group, the subjects were inoculated the second time with a vaccine derived from human blood plasma obtained from the Kitazato Therapeutic Research Institute. The third time, they were inoculated with a vaccine from the Chemo-Sero Therapeutic Research Institute derived from a second-generation vaccine organized ferment. The vaccine used for the second inoculation group was obtained from the Chemo-Sero Therapeutic Research Institute. Results were summarized as follows: 1) The primary vaccination group: (1) The number of the 153 subjects inoculated with the primary vaccination at the time of the second inoculation, 49 subjects (32%) tested positive for antibodies 3-4 months following inoculation. Thirty-two subjects (20%) tested positive 15-16 months following inoculation with a high rate among females. (2) Among 104 subjects inoculated the third time with the primary vaccination (those who tested negative the second inoculation of the above vaccine), 61 subjects (58.7%) tested positive for antibodies 8-9 months following inoculation with a generally high rate among females. Twenty-eight subjects (26%) tested 15-16 months after inoculation with a high rate among females between 20 and 30 years and among males between 40 and years. 2) The secondary group: Among the 38 subjects who were inoculated the second time with the secondary vaccination, 8 subjects (21%) tested positive for antibodies 5-6 months following inoculation, with a high rate among females in their 20's. 3) The rate of antibodies formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Basic investigation of saliva SIgA].

Saliva, which contributes to maintaining health in the oral environment, is affected by the physiological functions of the organism and their condition. Dental caries and periodontosis, both of which are oral diseases with frequent occurrence, require the presence of bacteria to occur. SIgA (secretory IgA), an immune globulin that is found in large quantities in substances secreted during salivation, has an antibacterial action. Thus, in conducting a basic investigation on the relationship between these factors, the author investigated what effect the speed of saliva secretion, a physiological factor of the saliva component, has on the SIgA value. Results showed that, regarding the relationship between the salivary SIgA value and the speed of salivary secretion, a negative correlation exists although this is weak in terms of relevance. The fact that the correlation displayed a tendency toward scattering indicates a need to pay attention when measuring the elements in the saliva to those factors that evidently have an effect on the composition of the saliva.

Humans↗

Clinical pharmacology of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine in patients with hematologic malignancies.

The pharmacokinetics of oral N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC), a lipophilic and deaminase-resistant derivative of 1-beta-D-arabinofuranosylcytosine (ara-C), were determined in patients with hematologic malignancies. The concentration of ara-C and 1-beta-D-arabinofuranosyluracil (ara-U), metabolites of PLAC, were measured by radioimmunoassay and gas chromatography-mass spectrometry-mass fragmentography, respectively. The concentration of PLAC was determined by measuring ara-C, which was derived from PLAC by hydrolyzation. In six patients given an oral bolus of PLAC (300 mg/m2), the plasma-disappearance curve of PLAC corresponded to a one-compartment open model, including first-order absorption. The peak plasma level was 22.9 +/- 6.4 ng/ml, and the predicted time to reach the peak level was 2.5 +/- 1.0 h. The elimination half-life was 3.8 +/- 2.7 h. The plasma ara-C level increased slowly to 6.9 ng/ml during the 1st 2-3 h after administration and remained over 1.0 ng/ml for 12 h. Plasma ara-U was detectable for at least 24 h, with a peak concentration of 376 ng/ml at 6 h. Urinary PLAC excretion was below the limit of detection (5 ng/ml) in all cases. Prolonged urinary ara-C and ara-U excretion was detected, but the total recovery rate was low (6.7% in 24 h) and varied between patients. In spite of the lipophilic nature of the drug, the PLAC concentration in the cerebrospinal fluid, measured at 3 or 6 h, was below the limit of detection in all four patients with no meningeal involvement. This study showed low but persistent levels of PLAC in plasma and tissues, with a continuous release of small amounts of ara-C, which demonstrated antitumor activity in patients with hematologic malignancies.

Adult↗

Lysis of human leukemic cells by monocyte-derived macrophages activated with interferon-gamma and interleukin-2.

Cytolysis of leukemic cells by peripheral blood-derived macrophages was examined by means of an in vitro 111In release assay. Monocytes prepared on culture dishes lyse YK-M2. However, when monocytes were cultured in vitro and transformed into macrophages, they lost most of their lytic activity. The addition of human recombinant interleukin-2 (rIL-2) on day 5 in culture enhanced the lytic activity significantly. Similarly, treatment of macrophages with human recombinant interferon gamma (rIFN-gamma) promoted the lysis of YK-M2 and K-562, although the extent of lysis was smaller than that by rIL-2. Macrophages activated with rIL-2 and rIFN-gamma also lysed human leukemic cells. Activated macrophages lysed leukemic cells of acute myelocytic leukemia more than acute lymphocytic leukemia cells. Macrophages derived from the peripheral blood of patients with leukemia were examined for their lytic activity against YK-M2. The patient's macrophages lysed more YK-M2 than did control macrophages when they were activated with rIL-2 and rIFN-gamma. The macrophages of two patients also demonstrated autologous leukemic cell lysis.

Adolescent↗

[Hepatitis B virus and epidemiological study on efficacy of HBIG and vaccine for the prevention of type B hepatitis after accidental exposures among medical staffs (2)].

The best method of preventing HBV is accurate perception on the part of the patient. There is a need for sufficient care regarding patient blood with HBsAg (+), HBeAg (+) and HBc high-antibody titer. The following is a report on a follow-up survey regarding antibody titer following dosages of HBIG 2 V and 1 V and administration of a vaccine along with dosage of HBIG 1 V. 1. Dosage of HBIG 2V: (Female) Antibody titer was recognized two days following dosage. It continued for two weeks and disappeared after four weeks. (2) (Male) Antibody titer was recognized one day following dosage but disappeared after two weeks. 2. Dosage of HBIG 1 V: (Female) Antibody titer (-) was recognized two days after dosage and nine days after dosage. It continued for about one month and disappeared after five months. 3. Administration of three vaccines and dosage of HBIG 1 V: (Female) Antibody titer was recognized two days after HBIG 1 V dosage and continued for 18 days but disappeared after three months. Antibody titer was recognized again after about eight months and showed signs of continuing for 13 months.

Female↗

[Basic investigation of saliva and serum SIgA].

The local immune mechanisms of which the IgA system is central are characterized by activity that is independent of the immune response of the body as a whole. Among these mechanisms, SIgA (secretory IgA) plays an important role. In measuring saliva/serum SIgA, the author used an EIA SIgA column set for saliva and for serum. Investigation of saliva SIgA concerned the correlation with saliva flow speed while investigation of serum SIgA concerned patients with oral dysfunctions and those inoculated with the HB preventive vaccine. A slightly negative correlation was observed between the saliva flow speed and the saliva SIgA value. Regarding serum SIgA, effect from the liver function was considered to be a factor among patients with oral dysfunctions. The antibody positive subjects among those inoculated with the HB vaccine are considered to reflect the response level of the antibody factor as well as individual differences in sensitivity and immune response. Among antibody negative subjects, however, there was a general tendency toward high values.

Humans↗

Candidacidal activity of monocyte-derived human macrophages: relationship between Candida killing and oxygen radical generation by human macrophages.

Freshly isolated human monocytes ingested and killed Candida albicans, and generated O2- H2O2 and .OH efficiently. When monocytes were cultured in vitro, these cells transformed into macrophages. Cultured monocytes retained their ingestive activity but lost their candidacidal activity almost completely after day 3. The release of O2- by monocytes decreased slightly with culture and that of .OH was markedly decreased on day 3 of culture. The activity of myeloperoxidase in the monocytes decreased with culture. These results suggested that the loss of candidacidal activity is due to the decrease of .OH generation and myeloperoxidase activity in cultured monocytes.

Blood Physiological Phenomena↗

The bactericidal mechanisms of polymorphonuclear leukocytes against Bacteroides fragilis: significance of the oxygen-dependent system.

The mechanism by which polymorphonuclear leukocytes (PMNs) kill ingested Bacteroides fragilis was examined using PMNs from patients with chronic granulomatous disease (CGD) which is an inherited disease characterized by the defect of their PMNs in oxygen-radical generation. The phagocytosis of B. fragilis by PMNs from CGD patients was comparable to that by normal PMNs. Although CGD cells killed B. fragilis to some extent, they did so less effectively than the normal PMNS. B. fragilis was killed by a xanthine oxidase system that generates oxygen radicals. When PMNs were incubated with opsonized B. fragilis, B. fragilis triggered the release of O2- and H2O2 from normal PMNs. Thus, normal PMNs appear to kill B. fragilis by both oxygen-dependent and oxygen-independent mechanisms.

Bacteroides fragilis↗

Oxygen radical generation by polymorphonuclear leucocytes of beige mice.

Oxygen radical generation was measured using peritoneal exudate polymorphonuclear leucocytes (PMN) from a strain of beige mice, an animal model of the Chediak-Higashi syndrome. These PMN have been shown to exhibit delayed microbial killing and impaired phagosome-lysosome fusion. The amount of superoxide anion released by the PMN of the beige mice was similar to that released by the PMN of the control mice. The PMN of beige mice generated slightly less hydrogen peroxide than the control. Hydroxyl radical (.OH) generation and luminol-dependent chemiluminescence were significantly lowered in beige PMN stimulated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA). Cytochalasin B-treated beige PMN showed a decreased ability to degranulate myeloperoxidase in response to OZ or PMA. We demonstrated the significant decrease in .OH generation and chemiluminescence in beige PMN, which might be one of the reasons to explain delayed microbial killing.

Animals↗

[Reproductive pharmacology of prostaglandins].

Effects of prostaglandins and their analogues in reproduction were investigated using rats and Japanese monkeys. Prostaglandin of the F series exerted uterine contractile, luteolytic, anti-nidation and abortifacient effects. Prostaglandins of the E series exhibited a potent uterine contractile effect, although their luteolytic, anti-nidation and abortifacient effects were much less potent than those of the PGF series. A comparison of animal and human data on prostaglandins and their analogues indicated a good cor-relationship between the uterine contractile effect in animals (rates and monkeys) and the abortifacient or labor inducing effect in humans.

Abortifacient Agents↗