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Biomedical subjects

H Nakada

Publications and source records attributed to H Nakada.

At least 109 records · Page 6Linked to original sources
PubMed1988

Production of monoclonal antibodies directed against carbohydrate moieties of cell surface glycoproteins.

Through the use of a technique for raising monoclonal antibodies, coupled with a solid-phase radioimmunoassay utilizing immobilized glycopeptides prepared from the surface membranes of the colorectal cancer cells (LS 180) used for the immunization, carbohydrate-directed monoclonal antibodies were obtained. One of the monoclonal antibodies, MLS 102, reacted immunohistochemically intensely with the colorectal cancer cell surface and the mucinous glycoproteins secreted by the cancer cells, but only weakly with normal colon tissue. The antigenic determinant recognized by MLS 102 was the carbohydrate moiety of glycoproteins with terminal sialic acid. The antigens defined by other monoclonal antibodies, MLS 103 and 104, were immunohistochemically detected in both normal colonic epithelial and cancer cells. These antibodies seemed to recognize the carbohydrate moieties of both glycoproteins and glycolipids. The method described in this report can be generally applied to raise cell surface carbohydrate-directed antibodies.

Animals↗
PubMed1988

Superoxide anion production by neutrophils in myelodysplastic syndromes (preleukemia).

Superoxide anion (O2-) production by neutrophils from 14 untreated patients with acute nonlymphocytic leukemia (ANLL) was significantly less than that of healthy controls (4.93 +/- 1.99 vx 6.20 +/- 1.53 nmol/min/10(6) neutrophils, p less than 0.05). In 10 patients with myelodysplastic syndrome (MDS), however, it was not significantly different from the control level although 6 of the 10 patients had low levels, when individual patients were compared with the lower limit of the control range. An inverse correlation between the O2- production of neutrophils and the percentage of leukemic cells in the marrow existed in ANLL (r = -0.55, p less than 0.01), but not in MDS. Three of 4 MDS patients who died of pneumonia prior to leukemic conversion showed a low level of O2- production. The impaired O2- production by neutrophils from some MDS patients, probably due to the faulty differentiation from leukemic clones, may be one of the causes of enhanced susceptibility to infection.

Aged↗
PubMed1988

[Clinical effects of K-18 (IgG-melphalan) in hypoplastic leukemia: a case report].

Five cases of hypoplastic acute myelocytic leukemia were treated with an IgG-melphalan conjugate, K-18. Eight tablets of K-18, containing 30 mg per tablet, were given daily. One patient, a 68-year-old female, obtained complete remission with a duration of 1.5 + months. Among the four remaining patients without remission, one showed a decrease in leukemic cells in the peripheral blood. No side effects of K-18 were observed except in one patient, showing a slight increase in serum GOT and GPT levels. Further studies with a large group will be necessary to clarify the effect of this drug on hypoplastic leukemia.

Administration, Oral↗
PubMed1988

[Chemotherapeutic effects in hypoplastic leukemia].

Clinical effects of a low dose of behenoyl ara-C (LD-BHAC) and K-18, an IgG-melphalan conjugate, were studied in hypoplastic leukemia (HL). Among 8 cases of HL treated with LD-BHAC regimen, in which 50 mg BHAC was administered daily by one-hour drip infusion for 14 days, 4 achieved complete remission (CR) and 2, partial remission (PR). The response rate (CR + PR) was 75%. Hematological toxicities were observed in most of the cases. The peak level of serum ara-C concentration, 3.62-18.9 ng/ml (mean: 11.74 ng/ml), was observed at cessation of infusion, and an ara-C level of 2.75-48.9 ng/ml (mean: 3.45 ng/ml) was still present in the blood 6 hours after cessation of infusion. Six cases of HL were treated with K-18. Eight tablets of K-18, containing 30 mg per tablet, were given daily. Two of 6 cases achieved CR with little hematological toxicities. LD-BHAC and K-18 can be expected in the treatment of hypoplastic leukemia and its related diseases such as hypoplastic preleukemia in the aged.

Adult↗
PubMed1987

Mucin-carbohydrate directed monoclonal antibody.

To raise monoclonal antibodies recognizing cancer-associated alterations of the carbohydrate structure of glycoproteins, Balb/c mice were immunized with human colonic cancer cells (LS 180 from ATCC). One of the generated hybridomas produced a monoclonal antibody that bound to the carbohydrate moiety of mucin-type glycoproteins from LS 180. The antibody did not bind to glycoproteins from another colonic cancer cell line, SW 1116, or to glycolipids from any of the colonic cancer cell lines. The antibody bound to ovine and bovine submaxillary mucins (OSM and BSM). NeuAc alpha 2----6Ga1NAc seemed to be involved in the epitope.

Animals↗
PubMed1987

Immunoelectron microscopic localization of dopamine beta-hydroxylase and chromogranin A in adrenomedullary chromaffin cells.

Dopamine beta-hydroxylase (DBH) was purified from bovine adrenal medullae. Rabbit IgG raised against DBH inhibited its activity by 80%. In an immunoblot analysis, the IgG specifically recognized two subunits of DBH the 72 and 75 KD components. Chromogranin A (CGA) also was purified from bovine adrenal medullae, and rabbit IgG against CGA recognized this chromogranin A in the immunoblot analysis. The intracellular distribution of DBH and CGA in bovine chromaffin cells was determined quantitatively by immunoelectron microscopy using post-embedding protein A-gold technique. DBH and CGA were localized exclusively on chromaffin granules. The binding of gold particles to these granules was saturable. The maximum number of gold particles bound to the granules roughly corresponded to the number of DBH or CGA molecules in the granules estimated biochemically. DBH was observed evenly in the periphery and in the dense matrix of the chromaffin granules.

Adrenal Medulla↗
PubMed1987

[Therapeutic effects of a combination of intermediate-dose cytosine arabinoside, adriamycin and vincristine in relapsed acute leukemia].

Eleven cases of acute leukemia, 8 relapsed and 3 refractory to a conventional induction chemotherapy, were treated with a combination of intermediate-dose cytosine arabinoside (ara-C), adriamycin (ADM) and vincristine (VCR). They consisted of 9 ANLL and 2 ALL. The therapeutic regimen consisted of 1-hour infusion of ara-C of a dose of 500 mg/m2 every 12 hours for 6 days from days 3 to 8, ADM, 40 mg/m2, on day 1 and VCR, 1.4 mg/m2, on day 2. Among 11 cases in which an evaluation was possible, 7 obtained complete remission (CR). The CR rate was 77.8% in the 9 cases of ANLL. The toxicity of this regimen included the following: conjunctivitis in 4 of 11 cases (36%), nausea and vomiting in 9 of 11 cases (91%) and hair loss in all cases, although no toxicities of the central nervous system of liver were observed. The mean level of serum concentration of ara-C was above 10 microM at 15, 30 and 60 minutes after the initiation of infusion. The therapeutic effect of this regimen consisting of intermediate-dose ara-C is expected to be useful not only in induction of refractory and relapsed acute leukemia, but also in the postremission therapy of CR cases.

Acute Disease↗
PubMed1986

Three molecular forms of a rat asialoglycoprotein receptor.

It has been reported that a rat asialoglycoprotein receptor is composed of three polypeptide chains with molecular masses of 43, 54, and 64 kilodaltons (43, 54, and 64-Kd forms) and that the first has a different primary structure from the latter two forms. Incorporation of [3H]leucine into these forms showed that no precursor-product relationship is found between the 54-Kd and 64-Kd forms. The half-life of the 43-Kd form (25 h) was shorter than those of the 54-Kd and 64-Kd forms (66 and 70 h, respectively). Glycopeptides of the three forms were prepared from rat livers previously labeled in vivo with [3H]glucosamine. Gel filtration analysis of the glycopeptides before and after endo H treatment revealed that they were all resistant to endo H. Alkali treatment did not change the elution position appreciately. These results indicate that the three molecular forms contained only complex oligosaccharide chains. The receptor was prepared from rat livers previously treated with tunicamycin in vivo and subjected to SDS-PAGE. A distinct band with a molecular mass of 33 Kd was observed. The receptor was also immunoprecipitated from rat hepatocytes in primary culture previously labeled with [35S]methionine and analysed by SDS-PAGE and fluorography. In addition to the major 43-Kd form, a band with a molecular mass of 41 Kd was found and tunicamycin treatment gave rise to a 33-Kd component, which is in good agreement with the receptor purified from tunicamycin treated rats. It is suggested that the 43-Kd form is synthesized as a 33 Kd polypeptide, cotranslationally glycosylated to form the 41 Kd component and then processed to the final 43-Kd form. We also think that the 43-Kd form could bind to asialoorosomucoid-Sepharose 4B without its carbohydrate chains.

Animals↗
PubMed1986

Biosynthesis and secretion of amyloid P component in rat liver.

Amyloid P component was isolated from rat liver and serum; its properties, biosynthesis, and glycosylation in the liver were investigated. The molecular weights of intracellular and serum amyloid P component were estimated to be 28,000 and 30,500, respectively. The two forms were immunologically identical, and kinetic study revealed a clear precursor-product relationship between them. The total mRNA was prepared from rat liver with or without turpentine treatment, and the RNA content of amyloid P component was estimated by the incorporation of [35S]methionine into the in vitro translation products. The turpentine treatment induced a marked increase in the level of translatable mRNA of the amyloid P component (approximately 46 fold), while the serum level of the protein elevated only moderately (approximately 1.7 fold). Most of the intracellular amyloid P component was sensitive to endo H. Various subcellular fractions were prepared from rat livers previously labeled in vivo with [35S]methionine. The protein prepared from the rough and smooth microsomes and heavy Golgi fraction were all sensitive to endo H, whereas that from the light Golgi fraction was a mixture of forms sensitive to and resistant to endo H. This result suggests that the processing of the mannosyl oligosaccharide chains and the subsequent addition of terminal sugars to convert the liver amyloid P component (28,000 daltons) to serum counterpart (30,500 daltons) were performed in the trans-Golgi region just before secretion of the amyloid P component.

Amyloid↗
PubMed1986

The (Na+, K+)ATPase of rat kidney: purification, biosynthesis, and processing.

(Na+, K+)ATPase was purified from rat renal outer medulla by concanavalin A- and wheat germ agglutinin-lectin Sepharose affinity chromatographies. The antibody, which was raised in rabbits, markedly inhibited ATPase activity. The monospecificity of this antibody was assayed by the Ouchterlony double immunodiffusion and Western blotting tests. The endoplasmic reticulum (ER)-rich, and Golgi-rich subfractions were prepared from the rat kidney microsomal fraction by sucrose density gradient centrifugation. On the immunoblot, the molecular weight of the alpha subunit in both fractions was 95 kilodalton (Kd); whereas, that of the beta subunit was 50 Kd in the ER-rich fraction and 54 Kd in the Golgi-rich fraction. When treated with endoglucosidase H, the 50 Kd component was converted to 38 Kd, but the 54 Kd component was endoglucosidase H resistant. These results suggest that the beta subunit (38 Kd) is glycosylated cotranslationally in the ER (50 Kd) then is converted to the mature type subunit (54 Kd) in the Golgi apparatus.

Amino Acids↗
PubMed1986

Aclarubicin in the treatment of elderly patients with acute nonlymphocytic leukemia.

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.

Aclarubicin↗
PubMed1986

[Low-dose 4N-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC) in the treatment of atypical leukemia].

Four cases of hypoplastic leukemia, one of acute myelocytic leukemia (M2) and one of RAEB-t were treated with a low-dose 4N-behenoyl-1-beta-D-arabinofuranosylcytosine (LD-BHAC) regimen, in which 50 mg BHAC was administered daily intravenously by one-hour drip infusion for 14 days. Among the 6 cases, three (2 hypoplastic leukemia and one M2) obtained complete remission and one (hypoplastic leukemia), partial remission. Response rates were 66.6% of all cases, and 75% of cases of hypoplastic leukemia. During treatment, cytopenia was observed in all cases and a decrease in bone marrow nucleated cell counts was recognized in the aged M2 patient with remission. Although side effects of the drug on the digestive system such as anorexia and nausea were observed in some cases, they were all controllable by conventional treatments. The serum concentration of ara-C was measured in 4 cases. The peak level of serum ara-C concentration, 3.62-18.9 ng/ml (mean: 11.74 ng/ml), was observed at the time of cessation of infusion of BHAC, and an ara-C level of 2.75-4.89 ng/ml (mean: 3.54 ng/ml) was still present in the blood 6 hours after the cessation of infusion. It was concluded that LD-BHAC was useful in the clinical management of atypical leukemia and acute myelocytic leukemia in the aged.

Adult↗