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Biomedical subjects

H Nagata

Publications and source records attributed to H Nagata.

At least 307 records · Page 17Linked to original sources

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↗

Light and electron microscopic studies of localized laryngeal amyloidosis.

We performed light and electron microscopic studies in a case of localized supraglottic laryngeal amyloidosis involving a 55-year-old woman. Tissue specimens were stained with hematoxylin and eosin, and alkaline Congo red with or without permanganate (KMnO4) treatment, and were also examined with peroxidase-antiperoxidase immunohistochemistry. Biopsy specimens from the epiglottis showed diffuse replacement of the subepithelial region by amyloid, which showed a typical green birefringence under polarized light. Tissue affinity for Congo red was persistent after the KMnO4 treatment. However, the tissue sections showed a positive reaction only to the anti-P component antibody. Electron microscopic studies revealed some disorders of the plasma cells, suggesting that these cells play an important role in focal production of amyloid fibrils.

Amyloid↗

Clinical evaluation of basic fetoprotein in testicular cancer.

We attempted to determine the efficacy of basic fetoprotein as a marker in testicular cancer. The levels of serum basic fetoprotein were studied in 58 patients (31 with seminoma and 27 with nonseminoma). Elevated levels were observed in 22 seminoma (71 per cent) and 15 nonseminoma (56 per cent) patients, while the levels of other markers (beta-subunit of human chorionic gonadotropin, alpha-fetoprotein and lactic dehydrogenase) remained normal in 6 seminoma (19 per cent) and 2 nonseminoma (7 per cent) patients. The levels of basic fetoprotein changed in relation to the clinical courses and they elevated again in 3 of 4 patients with recurrence. The concentration of basic fetoprotein in testicular cancer tissue was significantly higher than in the normal testis. Histological localization of basic fetoprotein in testicular cancer tissue was demonstrated immunohistochemically. Thus, basic fetoprotein was considered to be a useful serum marker for testicular cancer.

Antigens, Neoplasm↗

Increased lymphocyte transport by lipid absorption in rat mesenteric lymphatics.

The effect of olive oil administration on lymphocyte transport through mesenteric lymphatics was examined to see the possible involvement of nutritional absorption in lymphocyte traffic from the intestinal mucosa. After the olive oil administration to rats, remarkable increase in lymphocyte flux was observed within 2 h in lymph samples collected from rats with lymphatic fistula. The use of a high-speed microscopic video system made it possible to analyze accurately the lymphocyte transport in rapid movement that could not be detected by any of the ordinary video systems. The direct observation of mesenteric collecting lymphatics by this system showed an increment of lymphocyte transport from the intestinal mucosa by lipid absorption in 2 h. The contraction frequency of intestinal collecting lymphatics was also enhanced by olive oil administration. The densitometric analysis on video image was applied to estimate the extent of lipid absorption. The combination of a high-speed video system and the densitometric analysis revealed that the increase in lymphocyte flux occurred before lipid absorption reached its maximum and also demonstrated that the lymphocyte transport returned to control levels under the maximal absorptive condition. The results suggest that the fat absorption could be an important factor influencing the lymphocyte transport in the lymphatic system of intestine.

Absorption↗

[A study of the use of methotrexate, vincristine, cis-platinum, cyclophosphamide, adriamycin, bleomycin (MVP-CAB) in metastatic transitional cell carcinoma].

Eight patients with metastatic transitional cell carcinoma of the urinary tract were treated with the MVP-CAB regimen. All of them had bidimensionally measurable lesions. The MVP-CAB regimen consisted of cyclophosphamide 500 mg/m2, methotrexate 20 mg/m2, adriamycin 20 mg/m2, bleomycin 30 mg/body, and vincristine 1 mg/body on day 1, cis-platinum 50 mg/m2 on day 2, and prednisolone 20 mg/body on days 1-3, given every 3-4 weeks. A partial response was seen in five patients, minor response in one patient and no change in two patients. The response rate was 63% (5/8). The main toxic effect of the MVP-CAB regimen was leucopenia. In 75% of the patients there was a decrease in white blood cell count by not more than 2,000/mm3, but no severe complication was noted. In addition, mild nausea, vomiting, mild anorexia, alopecia and fever were found. However, these symptoms were transient. One patient died of pulmonary fibrosis induced by bleomycin after 3 cycles.

Adult↗

Sulfasalazine and its metabolites attenuate respiratory burst of leukocytes--a possible mechanism of anti-inflammatory effects.

The effects of sulfasalazine and its metabolites, 5-amino salicylic acid and sulfapyridine on respiratory burst of polymorphonuclear leukocytes were investigated by determining not only luminol-dependent chemiluminescence for the detection of myeloperoxidase-mediated active oxidants, but also lucigenin-dependent chemiluminescence for the detection of superoxide anion. The present study showed that sulfasalazine, 5-amino salicylic acid and sulfapyridine attenuated active oxygen species from polymorphonuclear leukocytes at the concentrations comparable to clinical doses. Therefore, it was concluded that anti-inflammatory effects of sulfasalazine can be explained by the ability of sulfasalazine and its degraded compounds to scavenge active oxidants from polymorphonuclear leukocytes.

Aminosalicylic Acids↗

Increased respiratory burst of leukocytes in inflammatory bowel diseases--the analysis of free radical generation by using chemiluminescence probe.

Respiratory burst of leukocytes was determined in Crohn's disease, intestinal Behçet's disease and ulcerative colitis by using chemiluminescence assay. Oxygen-derived free radicals of monocytes in Crohn's disease and those of polymorphonuclear leukocytes in intestinal Behçet's disease were significantly raised as compared with those of controls. In ulcerative colitis, respiratory burst activities of both polymorphonuclear leukocytes and monocytes were found to be highly associated with the disease activities. These results suggest that active oxygen species from leukocytes may participate in the formation of intestinal mucosal lesions in inflammatory bowel diseases via auto-oxidative process.

Adult↗

Action of 7-ethylcamptothecin on tumor cells and its disposition in mice.

Some biological effects of camptothecin (CPT) and its new derivative 7-ethylcamptothecin (ECPT) were studied. The drugs were effective against murine leukemia; ECPT was more effective than CPT. Ip administration of ECPT or CPT gave maximum treated/control values of 325% and 232%, respectively. The drugs also inhibited the growth of KB cells in vitro, 50% effective doses of 3.5 ng/ml of ECPT and 8.6 ng/ml of CPT, indicating the stronger activity of ECPT. Pharmacokinetic studies of the drugs in mice showed that ECPT had a longer biological half-life in the terminal phase and a larger amount remained in the plasma compared with CPT. After iv administration of ECPT, the drug accumulated in the intestine, suggesting that the main route of excretion of the drug is through the biliary tract. The study on cell cycle progression by flow cytometry suggested that the main effect of both drugs on L1210 cells was the blocking of G2-M phase. These results suggest that the main reasons for the superior antitumor activity of ECPT compared with CPT are as follows: (a) ECPT had a stronger growth-inhibiting activity against tumor cells, and (b) ECPT remained in the intestinal tract for a longer time and in higher amounts when administered in vivo.

Animals↗

Neurotoxicity of halogenated phenylacetylureas is linked to abnormal onset of rapid axonal transport.

A structure-activity study was performed to investigate the mechanism of neurotoxicity induced in rats by treatment with p-bromophenylacetylurea (BPAU). Phenylacetylurea and 7 derivatives were tested for their ability to induce hindlimb weakness after twice weekly administration in doses of 200 mg/kg, up to a cumulative maximum of 2000 mg/kg. In this test, BPAU and its chloro- analog were about equipotent, but none of the other analogs displayed any evidence of neurotoxicity. Since BPAU toxicity was believed to involve abnormalities in rapid axonal transport, selected analogs were examined in a transport experiment. None of the compounds led to alterations in the maximal rate of rapid anterograde transport, as measured after intraspinal injections of [35S]methionine in rats treated with 400 mg/kg of toxicant, 7 days earlier. However, both BPAU and its chloro- analog caused marked shortening of the delay between isotope injection and transport onset, an effect not seen with either of the two non-neurotoxic analogs tested. It is hypothesized that the accelerated transport onset is a key step in development of the neuropathy, possibly causing organelle abnormalities that interfere with turnaround and recirculation of transported particles.

Animals↗

Axonal transport in the motor neurons of rats with neuropathy induced by p-bromophenylacetylurea.

Axonal transport was studied in sciatic motor neurons of rats with neuropathy induced by p-bromophenylacetylurea (BPAU) in dimethylsulfoxide solution. Control rats were treated with the vehicle alone. To label rapidly transported proteins, the rats received an injection of 35S-methionine into the ventral horn of the spinal cord at the L1 vertebral level. Radiolabeled protein was collected at ligatures applied on the sciatic nerve at intervals thereafter. In animals with severe motor weakness owing to treatment with BPAU, 400 mg/kg, there was evidence of increased delivery of labeled protein into the axon during the early period after isotope injection, but reduced delivery later. A dose-dependent decrease in the amount of labeled protein recirculated by retrograde axonal transport was also noted. A significant reduction in the amount of protein transported retrogradely was also detected during the latent subclinical phase of the neuropathy. The velocity of rapid anterograde transport, examined in unligated sciatic nerves, was unaffected by BPAU treatment. However, the lag time between precursor injection and the onset of transport was shorter in BPAU-treated rats than in controls. This effect was not explainable on the basis of fluctuations in core body temperature. The results are consistent with the view that disturbances of rapid anterograde and retrograde transport play a role in the peripheral neurotoxicity of BPAU. Attention is directed to the possibility that the transport disturbances and the subsequent neuropathy are related to alterations in the processing of rapidly transported membrane-limited organelles in the nerve cell bodies.

Animals↗