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Biomedical subjects

T Kokawa

Publications and source records attributed to T Kokawa.

50 records · Page 3Linked to original sources

[Analysis of adhesive proteins on the surface membrane of platelet in malignant neoplasm].

Flow cytometry was used to detect fibrinogen (platelet associated fibrinogen: PAFbg) and fibronectin (PAFn) on the surface membrane of platelets in leukemia (9 cases), lung cancer (15 cases) and hepatoma (8 cases) patients (by one color analysis method), and simultaneously to investigate the binding of monoclonal anti-glycoprotein (GP) IIb/IIIa and anti-GP Ib antibodies (by two color analysis). All patient groups showed higher Fbg values than the normal control group, but no differences were found between patient groups. The values of Fbg and Fn showed a correlation, but the pattern of binding did not show a regular tendency in any patient group. There also was no significant correlation between Fbg values and the positive percentage of monoclonal anti-GPIIb/IIIa and anti-GPIb antibodies, and the binding of Fbg did not inhibit that of monoclonal antibody. The results suggest the following. 1. There are no differences in platelet activation in leukemia, lung cancer and hepatoma patients, and the degree of platelet activation is decided by the degree and the kind of stimulation. 2. The increase of both PAFbg and PAFn prove to the existence of activated platelet.

Blood Platelets↗

[Chronic ITP with a remarkable response to vitamin C administration after splenectomy].

This report deals with a case of 23-year-old woman with chronic idiopathic thrombocytopenic purpura (ITP) showing a favorable response to vitamin C (VC) administration. She was treated with glucocorticoids and immunosuppressants, whereas inadequately controlled with its tolerable dosage. Next, she underwent splenectomy. However, there were only transient effects on platelet counts, so the therapy with ascorbate was carried out according to the report by Brox et al. The platelet counts increased to 20 x 10(4)/microliters after 4 months. Side effects of VC therapy did not occur.

Adult↗

[Analysis of anti-platelet antibody and platelet volume in idiopathic thrombocytopenic purpura].

We investigated platelets and plasma from patients with idiopathic thrombocytopenic purpura (ITP) to elucidate the antigenic determinants at which their autoantibodies are directed, and studied the relationship between anti-platelet antibody and platelet volume. We used flow cytometry to detect platelet-associated IgG (PAIgG), C3 (PAC3), IgM (PAIgM) and platelet volume, and also to determine the binding rate of monoclonal anti-platelet antibodies in patients with ITP. The following results were obtained. 1. Both anti-GPIIb/IIIa autoantibodies (21 of 71 patients) and anti-GPIb autoantibodies (3 of 71 patients) were found in ITP. 2. The decrease in platelet count in patients without anti-GPIIb/IIIa autoantibodies was significant. 3. The increase in platelet volume was found more frequently in patients with a platelet count less than 50,000 and in untreated patients. 4. There was a positive correlation between the platelet volume and PAIgM in patients with a platelet count less than 30,000 and high levels of PAIgM.

Adolescent↗

Effects of EDTA on the membrane glycoproteins IIb-IIIa complex--analysis using flow cytometry.

We developed new monoclonal antibodies (NNKY1-32, NNKY2-6, NNKY2-18) that react with a determinant specific to the GPIIb-IIIa complex, and studied the distribution of GPIIb/IIIa on the platelet surface in vivo and some factors that influence the structure of GPIIb/IIIa using flow cytometry. 1. The surface of large platelets is richer in GPIIb/IIIa than that of small platelets. 2. Incubation of intact platelets with EDTA at 37 degrees C causes progressive dissociation of GPIIb-IIIa complexes, and this influence is marked in small platelets. 3. Addition of Ca2+ or Mg2+ to dissociated GPIIb-IIIa complexes causes reassociation, and additionary ADP after the cation treatment further increases the binding of monoclonal antibodies. 4. Prolonged incubation of intact platelets with EDTA at 37 degrees C induces a peculiar change of structure in the GPIIb/IIIa.

Antibodies, Monoclonal↗

[Coenzyme Q10 in cancer chemotherapy--experimental studies on augmentation of the effects of masked compounds, especially in the combined chemotherapy with immunopotentiators].

Immunopotentiators may mitigate the depression of immunological function caused by the cancer itself or by chemotherapeutics. However, it has been found that these immunopotentiators reduce the metabolic activity of the host against drugs, including "masked" chemotherapeutics, which might be activated by metabolization in the body. Reported here is the result of serial experiments carried out on the activation of cyclophosphamide (CPM) in tumor-bearing animals, pretreated with phenobarbital, a drug-metabolizing enzyme inducer, and coenzyme Q10, a physiological activator of the electron transfer system in mitochondrias, in combination with immunopotentiators. Female Donryu rats (120 g body weight) implanted with Yoshida Sarcoma cells (YS) (2.5 X 10(6) i.p.) were treated with CPM (160 mg/kg X 1 i.p.), 84 hrs after implantation; the levels of the normustard-like substances (active metabolites of CPM) were serially measured. Some of the animals were also treated with PSK (125 mg/kg X 5 i.p.), a proteinpolysaccharide immunopotentiator obtained from mycelia of the Coriolus vesicolor, or with OK-432 (10 KE/kg X 5 i.m.), a streptococcal immunopotentiator. The results obtained were as follows: The blood levels of the normustard-like substances were lowered, i.e. the CPM activation was depressed in the YS-bearing rats and the depression was markedly intensified by PSK or OK-432 administration. Phenobarbital (40 mg/kg X 3 i.p.) or coenzyme Q10 (5 mg/rat X 5 i.p.) administration could mitigate the depression of the blood levels caused by the immunopotentiators, and the combination of phenobarbital with coenzyme Q10 could recover the blood levels up to those of the YS-bearing control rats, or even higher. YS-implanted (i.p.) rats treated with CPM+ immunopotentiators+coenzyme Q10 survived longer than those treated with CPM+immunopotentiators. These findings suggest the usefulness of coenzyme Q10 for the enhancement of cancer immunochemotherapy using masked compounds combined with immunopotentiators; all the more so, because coenzyme Q10 has also an immuno-stimulating effect, moreover, it presents almost no side effects in clinical application.

Animals↗

[Laboratory and clinical studies of ceftizoxime in pediatrics (author's transl)].

Laboratory and clinical studies were performed as follows on ceftizoxime (CZX), a new cephalosporin antibiotic. 1. Susceptibility of clinically isolated bacteria to CZX and cefotiam (CTM) or sulbenicillin (SBPC). Antibacterial activities of CZX and CTM were compared against S. aureus, E. coli, K. pneumoniae, E. cloacae, H. influenzae and E. aerogenes; CZX was compared with SBPC against Ps. aeruginosa. CZX and CTM were nearly equal in activity against S. aureus, but CZX was found to be more active than CTM by 1--10 tubes against E. coli, K. pneumoniae, E. cloacae, H. influenzae and E. aerogenes. Against Ps. aeruginosa, CZX and SBPC were nearly equal in activity. 2. Serum concentration and urinary recovery. Serum concentrations of CZX were measured in 6 patients given CZX for prophylactic purpose during cardiac catheterization. In 2 patients given 20 mg/kg of CZX intravenously, the average serum concentration was 38.9 micrograms/ml at 30 minutes after intravenous bolus injection. In 3 patients given 10 mg/kg of CZX by intravenous drip infusion, the peak average serum concentration was 28.1 micrograms/ml at the end of infusion. Urinary recovery in 2 patients tested was 81.1% and 92.5% until 6--7 hours after intravenous bolus injection. 3. Clinical efficacy. CZX was given intravenously to 24 patients in doses of 30--111 mg/kg (57.1 mg/kg on an average) t.i.d. or q.i.d. for 3--16 days (5.5 days on an average): 1 with lacunar tonsillitis, 4 with acute bronchitis, 12 with pneumonia, 2 with enterocolitis, 2 with soft tissue infection, 2 with lymphadenitis and 1 with UTI. The overall efficacy rate was 95.8%, i.e., efficacy was excellent in 10 (41.7%), good in 13 (54.2%), and poor in 1 (4.2%). Bacteriological efficacy was excellent, i.e. 21 of the 23 strains disappeared. One patient had mild and transient diarrhea, but no other laboratory abnormalities were observed during treatment. The above results suggest that CZX is 1 of the most useful antibiotics for treating pediatric infections, especially due to Gram negative bacteria.

Age Factors↗

[Laboratory and clinical studies of cefmenoxime in the pediatric field].

Laboratory and clinical studies were performed on cefmenoxime (CMX), a new cephalosporin antibiotic, and the following results were obtained. 1. Susceptibility of clinically isolated bacteria to CMX and cefotiam (CTM) or cefazolin (CEZ) Antimicrobial activity of CMX was compared with that of CTM and CEZ against S. aureus, S. epidermidis, S. pneumoniae, H. influenzae and E. coli. CEZ and CTM were more active than CMX against S. aureus, S. epidermidis and S. pneumoniae. But CMX was found to be more active by 1-10 tubes than CEZ and CTM against H. influenzae and E. coli. 2. Clinical efficacy. CMX was intravenously administered to 19 patients; 3 with lacunar tonsillitis, 2 with acute bronchitis, 8 with bronchopneumonia, 3 with UTI, 1 with septicemia, 1 with acute panperitonitis, 1 with S.S.S.S. at daily doses of 30-115 mg/kg (64.6 mg/kg on an average) t.i.d. or q.i.d. for 3-17 days (6.1 days on an average). The overall efficacy rate was 94.7%, i.e., efficacy was excellent in 10 cases (52.6%), good in 8 cases (42.1%), and poor in 1 case (5.3%). Bacteriological efficacy was good, i.e. 16 of the 19 strains disappeared. Transient eosinophilia was observed in 1 patient, but no other laboratory abnormality was observed during treatment. The above results suggest that CMX is 1 of the useful antibiotics in treatment of pediatric infections, especially due to Gram negative bacteria.

Adolescent↗

Increased body movements during sleep in Gilles de la Tourette syndrome.

Overnight sleep polygrams were recorded form 9 patients with Gilles de la Tourette syndrome (GTS). Six of 9 patients had abnormal electroencephalograms, but no specific abnormalities were detected. Body movements and twitch movements during sleep were analyzed. At all stages of sleep, body movements during sleep were more frequent in cases of GTS than those in normal controls. Twitch movements in stage REM of sleep were significantly increased in GTS. These results are consistent with the idea that GTS is due to an imbalance between the central neurotransmitters, catecholamine and serotonin.

Child↗

[Clinical experience with cefroxadine in bacterial infection of children (author's transl)].

In order to evaluate effectiveness of cefroxadine (CXD) in the treatment of bacterial infections of children, the clinical studies were carried out. CXD was orally administered to 30 patients at daily dose of 27.5 approximately 50.0 mg/kg (average 32.3 mg/kg) in 3 approximately 4 divided dose for 3 approximately 10 days (average 4.9 days). The overall efficacy rate in 30 cases was 93.3%, i.e., excellent 22 (73.3%), good in 6 (20.0%), fair in 1 (3.3%) and poor in 1 case (3.3%). Drug eruption and transient eosinophilia were observed in 1 case each out of 30 cases (6.7%), but any other abnormality was not observed throughout this series. Based on the above results, CXD was thus considered to be a useful antibiotic in treatment of pediatric infections.

Bacterial Infections↗

Characterization of a novel activation-specific antiplatelet monoclonal antibody.

We developed a murine monoclonal antibody (KmT-50) which binds to a protein expressed on the surface of human platelets after activation. KmT-50 is an immunoglobulin G1 monoclonal antibody that recognizes a 50-kD antigen localized in intracellular organelles and the open canalicular system of unstimulated platelets. After platelets were stimulated, the antigen was secreted via the surface-connected canalicular system and exposed on the platelet membrane. KmT-50 bound not only to human platelets, but also to rabbit and monkey platelets. This new antibody may be useful for experimental studies on thrombosis and hemostasis.

Animals↗