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Biomedical subjects

M Fujimaki

Publications and source records attributed to M Fujimaki.

At least 55 records · Page 3Linked to original sources
PubMed1994

Low serum aminotransferase activity in patients undergoing regular hemodialysis.

Of 150 patients undergoing regular hemodialysis (HD), 14 (9.3%) and 12 (8.0%), respectively, showed low serum activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). An investigation was conducted to elucidate the underlying mechanisms in 20 patients with low serum AST and/or ALT activity. Fifty-five percent of the patients with low aminotransferase activity manifested serum levels of pyridoxal phosphate (PLP) that were lower than normal. Serum PLP levels correlated neither with AST nor with ALT activity. Oral administration of vitamin B6 to the cases with low aminotransferase activity resulted in an increase in pre-hemodialysis aminotransferase activity. Addition of vitamin B6 in vitro to the sera from the patients with low aminotransferase activity did not increase the values when the added vitamin B6 was within the physiological range, but did increase when added in larger (pharmacological) amounts. However, aminotransferase activity increased, but PLP levels remained unchanged when these values were compared before and after HD. On the other hand, guanase being within the normal range in all cases studied, did not change after HD. Although our study does not correlate with vitamin B6 deficiency, but rather with some uremic substance(s) which interfere(s) with the enzyme reaction as a cause of low aminotransferase activity, the fact that less than 10% of our patients showed low AST and/or ALT points to the latter possibility, suggesting the need of further study.

Adult↗
PubMed1994

TNF receptor number-dependent cytotoxicity to TNF-resistant human esophageal cancer cell lines by combination with recombinant human necrosis factor and hyperthermia.

The synergistic effect of recombinant human tumor necrosis factor (rh-TNF) and hyperthermia on five established cell lines of human esophageal cancer (SGF series) was analyzed by in vitro assays. The SGF cell lines were either resistant or slightly sensitive to rh-TNF. However, they became highly sensitive to rh-TNF even at as low a concentration as 10 U/ml and dose-dependently when combined with hyperthermia (43.5 degrees C, 60 min). This result was due to synergistic effects of rh-TNF and hyperthermia, and the degree of the effect increased with the hyperthermic temperature and TNF concentration. The number of TNF receptors per cell varied widely from cell line to cell line, from 4,400 to 23,100, which did not correlate to the extent of cytotoxicity by rh-TNF alone. The degree of synergistic effect of rh-TNF and hyperthermia was evaluated quantitatively in terms of a Synergistic Index (S. I. = Predicted cell viability/Experimental cell viability): A significant correlation was found between the logarithmic S. I. and the number of TNF receptors. These findings indicated that the combination of rh-TNF and hyperthermia produced a significant antitumor effect even on the cell lines poorly sensitive to TNF in a receptor-dependent manner, although the cellular sensitivity to TNF alone was not directly correlated to the number of TNF receptors.

Drug Screening Assays, Antitumor↗
PubMed1994

[Fluctuations of tissue-type plasminogen activator.plasminogen activator inhibitor-1 complex in patients with DIC].

Plasma levels of tissue-type plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor-1 antigen (PAI-1:Ag), the active form of PAI-1 (active PAI) and t-PA.PAI-1 complex (PAI-C) were analyzed in 7 patients with disseminated intravascular coagulation (DIC) syndrome. The levels of t-PA:Ag and PAI-C decreased after amelioration of DIC in 6 patients whose underlying disease improved, but their PAI-1:Ag and active PAI showed various fluctuations. The levels of t-PA:Ag and PAI-C showed a good correlation of r = 0.885. The levels of t-PA:Ag or PAI-C showed an inversed correlation with platelet counts, and correlations with the levels of plasmin.alpha 2PI complex, D dimer and E fragments of FDP. It was considered that plasma levels of PAI-C reflected levels of t-PA released from the endothelial cells, which was related to acceleration of fibrinolysis in DIC patients with improved underlying disease. On the other hand, these levels remained high in a patient whose underlying disease did not improve after recovering from DIC. It was considered that the stimulation of endothelial cells by cancer cells continued to exert an effect.

Disseminated Intravascular Coagulation↗
PubMed1993

Anti-idiotypes against an anti-haloperidol antibody bind to sigma receptors.

Anti-idiotypic monoclonal antibodies that interact with the binding site of sigma receptors were generated. First, BALB/c mice were immunized with a haloperidol-bovine serum albumin conjugate, and monoclonal anti-haloperidol antibodies that recognize the piperidinyl moiety of haloperidol molecule were obtained. Second, for generation of anti-idiotypic antibodies, BALB/c mice were immunized with the anti-haloperidol monoclonal antibodies coupled to keyhole limpet hemocyanin. Anti-idiotypic antisera and three hybridomas secreting anti-idiotypic monoclonal antibodies were obtained. All of them were shown to inhibit [3H]haloperidol binding to the anti-haloperidol antibodies. The anti-idiotypes were potent in displacing the binding of [3H]haloperidol to rat brain sigma receptors. Furthermore, they significantly immunoprecipitated the sigma receptors from a detergent-solubilized preparation. These findings demonstrate the generation of anti-idiotypic monoclonal antibodies specifically interacting with membrane-bound and solubilized sigma receptors.

Animals↗
PubMed1993

[Clinicopathological evaluation of high-range hyperthermia for advanced thoracic esophageal carcinoma].

The effectiveness of high-range hyperthermia over 45 degrees C for advanced esophageal carcinoma was clinicopathologically evaluated. Fifty-eight patients with advanced thoracic esophageal carcinoma were treated with radio-chemotherapy. They were divided into two groups: group I included 32 cases, all of whom received hyperthermia (13 cases: high-range hyperthermia); group II included the other 26 cases. The patients were given 2 Gy/day for a total of 15 sessions in 3 weeks. Bleomycin and cisplatin in combination with 5-fluorouracil have been employed as chemotherapy. Hyperthermia was performed twice a week for a total of 6 sessions. Intraluminal heating was done using Japan Crescent Inc. IH-500 T (RF, 13.56 MHz), with an intraesophageal applicator and two extra-corporeal applicators on the chest and the back. Concerning local effects, the efficacy rate was 81.3% in group I (high-range: 92.9%), and 42.3% in group II. The histologic effectiveness, when Grade 2 and 3 are determined as histologically effective, were 64.3% (high range: 85.7%) and 50.0% in group I and II, respectively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Immunological abnormalities in HIV-free haemophiliacs.

Since some haemophiliacs manifest profound immunodeficiency with no evidence of human immunodeficiency virus type 1 (HIV) infection, we measured the circulating immune complex (CIC) level in sera obtained from haemophiliacs and addressed the question of whether viral infection is associated directly or indirectly with enhanced CIC production. While more than 90% of HIV-positive individuals had a high level of CIC, around 60% of seronegative ones also showed CIC levels comparable to those of seropositive patients. These sera activated fresh complement in vitro. The patients infected with either HIV or Hepatitis C virus (HCV) or both showed higher frequency and concentration of serum CIC than those free of either pathogens. It is worth noting, however, that 64% of patients with no evidence of infection with HIV or HCV produced significant amounts of CIC. Among the infectious viruses examined, parvovirus is considered as one of the pathogens associated with CIC synthesis, since all the haemophiliacs including the HIV-free patients who had been supplied with heated coagulation factors for several years from birth carried antibodies to parvovirus B19. Strikingly, 60% of the children in this category were positive for CIC, suggesting the possible contribution of parvovirus infection to CIC formation.

Adolescent↗
PubMed1993

Establishment of HIV-1-producing cells from peripheral mononuclear cells cultured with normal human serum.

Normal human serum (NHS) contributed to the establishment of cells producing HIV-1 under the conditions of coculture of peripheral mononuclear cells (PMC) from HIV-1 seropositive patients and of PHA-prestimulated or -non-stimulated PMC from seronegative healthy donors. No addition of IL-2 and Polybrene was necessary. Since, in the case 90101, the mitochondrial displacement-loop DNA showed identical sequences in the established cells and the HIV-1 seropositive patient's cells, it can be asserted that the HIV-1-producing cells originated from the patient. These cells are still releasing HIV-1-virion more than one year after their establishment.

Adult↗
PubMed1993

[Fluctuation of plasma levels of fibrinogen degradation products, fibrin degradation products and total fibrin/fibrinogen degradation products in patients with DIC].

Ten patients with disseminated intravascular coagulation syndrome (DIC) were analyzed using three enzyme linked immunosorbent assays (ORGANON TEKNIKA, Belgium) for fibrin degradation products (FbDP), fibrinogen degradation products (FgDP) and total fibrin/fibrinogen degradation products (TDP). A significant elevation in each parameter and a significant depression of FgDP/FbDP (g/b) ratio were observed in the patients in early stage of DIC, comparing with normal individuals (p < 0.001 and p < 0.01). These results suggested that both fibrinolysis and fibrinogenolysis were marked accelerated, with a superiority in fibrinolysis in those patients. The levels of these parameters decreased and the g/b ratio increased with the passage of the clinical courses in five patients who were improved. Although in five deteriorated cases, the levels were kept high and their g/b ratio showed low continuously. These findings suggested that separated monitoring of fibrinolysis or fibrinogenolysis was useful to study patients with DIC and g/b ratio could be regarded as a helpful indication of therapeutic effects.

Disseminated Intravascular Coagulation↗
PubMed1993

[Evaluation of an enzyme-linked immunosorbent assay for the determination of prothrombin fragment F1.2 (Dade Prothrombin Fragment F1.2 ELISA: Baxter Diagnostics Inc., U.S.A.) using micro-titer plate].

Prothrombin fragment F1.2 (F1.2) is a new molecular marker indicating acceleration of blood coagulation. We evaluated a new assay of F1.2 measurement using a micro-titer plate (Dade Prothrombin Fragment F1.2 ELISA: Baxter Diagnostics Inc., U.S.A.). The assay obtained satisfactory results in intra-assay reproducibility test, inter-assay reproducibility test, dilution linearity test and in vitro recovery test. Normal values of plasma F1.2 were 0.16 +/- 0.09 nmol/l (mean +/- SD) in 108 healthy individuals. Differences in the levels between the sexes were not significant. In patients with DIC (n = 22), plasma F1.2 levels were significantly higher than in normal healthy individuals and were correlated with the levels of thrombin-antithrombin III complex. These findings suggest that this F1.2 assay using a micro-titer plate is clinically useful for the evaluation of the therapeutic effect and diagnosis of hypercoagulable states like DIC.

Adolescent↗
PubMed1993

[New useful parameters or makers in diagnosis and condition. Analysis of disseminated intravascular coagulation--mainly molecular markers].

New assays for thrombin-antithrombin III complex, plasmin-alpha 2-plasmin inhibitor complex, FDP-D-dimer, t-PA/PAI-1 complex and prothrombin fragment F1+2 are reviewed as molecular markers for disseminated intravascular coagulation (DIC). These are sensitive to early stage indication of DIC. Fluctuation of their levels was also relative to the state of DIC. It is therefore believed that they will play an important role in the diagnosis of DIC, as solid members of its parameter. On the other hand, t-PA/PAI-1 complex is suggested to be the complication marker of DIC, such as multiple organ failure (MOF), as its level was thought to reflect endothelial cell stimulation during DIC.

Antifibrinolytic Agents↗
PubMed1993

[Levels of serum lactate dehydrogenase and its isozymes with relation to clinical features of pneumocystis carinii pneumonia in acquired immunodeficiency syndrome patients].

The clinical courses of 9 patients with acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis carinii pneumonia (PCP) were followed to investigate the clinical significance of the measurement of various parameters such as serum lactate dehydrogenase (LDH). The mean duration of symptoms before diagnosis was 20 days, and the median duration of therapy was 29.5 days. Serum LDH activity increased in 8 of 9 cases. The isozyme pattern in all cases was characterized by high LDH3 values from the early stage. However, inflammatory markers did not increase in most cases. There were good correlations between the levels of LDH, clinical course, and PaO2.

AIDS-Related Opportunistic Infections↗
PubMed1992

Fluctuations in plasma levels of thrombomodulin in patients with DIC.

Plasma thrombomodulin (TM) has attracted considerable attention as a marker of endothelial cell membrane injury. We examined fluctuations in plasma TM levels in patients receiving therapy for the disseminated intravascular coagulation syndrome (DIC) using an enzyme immunoassay. Sixty healthy controls and 18 patients with DIC were studied. The mean +/- SD of the TM values initially measured immediately after the onset of DIC was 42.00 +/- 20.85 ng/ml, which was markedly increased as compared with the control value of 15.36 +/- 4.85 ng/ml (p < 0.001). Fluctuations in the TM levels over time were studied after dividing the patients according to the presence or absence of improvement in the underlying disease and improvement or lack thereof in the coagulation findings. Group I showed improvement in both categories, Group II showed improvement only in the latter, and Group III showed no improvement in either category. In Group I, the mean +/- SD of initial measured TM levels was 37.02 +/- 10.12 ng/ml and the mean of final values decreased to 58.9% of the initial value. This decrease was significant by paired Student's t-test (p < 0.01). The initial value in Group II was 45.86 +/- 18.86 ng/ml and the final values increased to 117.0% of the initial values, this difference was not significant. The initial value in Group III was 44.48 +/- 21.53 ng/ml and the final values increased to 143.4% of the former. This increase was significant by paired Student's t-test (p < 0.05). The difference in % fluctuations between Group I and Group III was significant by Wilcoxon's test (p < 0.01). These results suggest that the measurement of plasma TM can be useful in the management of DIC.

Adolescent↗
PubMed1992

Stereoselective disposition and tissue distribution of carvedilol enantiomers in rats.

After intravenous bolus injection of rac-carvedilol at 2 mg/kg to the rat, the (+)-(R)- and (-)-(S)-enantiomer levels in the blood and tissues (liver, kidney, heart, muscle, spleen, and aorta) were measured by stereospecific HPLC assay. As compared with the (+)-(R), the (-)-(S) had a larger Vdss (3.32 vs. 2.21 liter/kg), MRT (33.4 vs. 25.6 min), and CLtot (96.1 vs. 83.8 ml/min/kg). AUC comparison after iv and po administration showed systemic bioavailability of the (-)-(S) to be about half that of its antipode, explained by the fact that the free fraction of the (-)-(S) in blood was 1.65-fold greater than that of the (+)-(R). Tissue-to-blood partition coefficient values for the (-)-(S) were 1.6- to 2.1-fold greater than those for the (+)-(R) in all tissues, showing that the (-)-(S) accumulates more extensively in the tissues. These results were consistent with the greater Vdss for the (-)-(S) estimated from systemic blood data. The stereoselective tissue distribution of carvedilol enantiomers results from an enantiomeric difference in plasma protein binding rather than in tissue binding.

Animals↗
PubMed1992

[Evaluation of novel assays for the detection of crosslinked fibrin degradation products in whole blood by the agglutination of the red blood cells].

We evaluated the clinical significance of two novel assays for the detection of crosslinked fibrin degradation products (XDP) in whole blood using the agglutination of the red blood cells (SimpliRED D dimer and SimpliRED D dimer-500, AGEN, Australia). XDP made serially by plasmin in vitro, were detected by the SimpliRED D dimer assay, but fibrinogen degradation products showed weak reactivity. Ten of the fifty four clinical samples collected with EDTA-2K, changed to positive on these assays after overnight incubation at 4 degrees C. Anemia and hemolytic samples had no effect on the assay results. The results obtained by the SimpliRED D dimer were negative for the normal subjects (n = 50) without exception. In our study, 81% and 95% of the patients, who showed abnormal levels of XDP in plasma and E fragments in serum respectively, were positive on the SimpliRED D dimer assay. The assay was as sensitive as the Rapidia-D dimer assay. In conclusion, the SimpliRED D dimer assay was clinically useful as a screening assay for the diagnosis of hypercoagulable and fibrinolytic states, since it could be performed simply and quickly.

Adult↗
PubMed1992

Herpes simplex virus type 1 and human immunodeficiency virus type 1 antigens in platelets from a hemophilia B patient with human immunodeficiency virus type 1-related thrombocytopenia.

We analyzed platelet-associated antigens from a hemophilia B patient with human immunodeficiency virus type 1 (HIV-1)-related thrombocytopenia. Two bands appeared at 31,000 and 37,000 daltons in the platelet lysate after reaction with autologous serum in SDS-PAGE and Western blots. The band at 37,000 daltons was obtained using anti-herpes simplex type 1 (HSV-1) rabbit antiserum. Doublet bands at 36,000 and 37,000 daltons also appeared after reaction with HSV-1 seropositive human serum. The band at 31,000 daltons appeared after reaction with anti-HIV-1 rabbit serum. These results suggest that the platelet-associated antigens in this patient are components of both HSV-1 and HIV-1 antigens. In addition, acyclovir decreased his PAIgG level and increased his platelet count, and zidovudine increased his platelet count. Thus, we concluded that each of the platelet-associated antigens is partially responsible for the thrombocytopenia by causing deposition of immune complexes in this patient.

Acyclovir↗
PubMed1992

[Hyperthermia for cancer with dextran magnetite using tubular implants].

Dextran magnetite particles (Meito Sangyo Corp.) are an aqueous magnetite zol and a nanometer complex consisting of dextran chains surrounding a core of ultrafine iron oxide. The tubular implants were made with polyester tube (3 mm diameter, 20 mm length) filled with DM aqueous zol (29%w/v). The temperature of an agar phantom with implants was measured in the inductive field. Heating was effected by creating an electromagnetic field with a 7 kW generator operating at 500kHz (Yamamoto Vinyter). The temperature was elevated 3.4 degrees at a distance of 5 mm from the implant at an inductive power of 2.6 kW. An area of 20 x 20 mm was heated while changing the power, the number of implants, and their arrangement. Selective heating of cancer was considered possible by inductive heating at 500 kHz and DM implants. Since the DM aqueous zol configuration can be readily changed, treatment of various cancers is possible.

Dextrans↗
PubMed1992

[Activities of antithrombin III and heparin cofactor II in patients with pathologic blood coagulation conditions].

To investigate the physio-pathological functions of HC-II, assays for HC-II and AT-III were performed simultaneously on the samples from patients with DIC, liver dysfunction or renal disease from the three view points of consumption, production and loss of AT-III and HC-II. For the AT-III activity, two kinds of assays were applied: the automatic chromogenic substrate method and a newly developed clotting method which receives no effects from HC-II activity. The activity of HC-II was significantly lower than that of AT-III in patients with either DIC or liver dysfunction. However, no significant difference between HC-II and AT-III activities in patients with either thrombosis or renal disease. There were high correlations between HC-II and AT-III activities were found in the patients with liver dysfunction, suggesting that low activity was due to decreased production of HC-II and AT-III in the liver. It will be necessary that elucidation of the significant functions of HC-II not only in coagulation and hemostasis but also in regulation of local inflammation and invasion of neoplasm is necessary.

Adult↗