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Biomedical subjects

S Furusawa

Publications and source records attributed to S Furusawa.

At least 163 records · Page 9Linked to original sources
PubMed1987

A novel method to investigate the heterocliticity of antibodies.

Monoclonal and anti-dinitrophenyl and anti-trinitrophenyl IgE antibodies were used to measure heterocliticity using competitive inhibition assays with homologous and heterologous haptens. The antibodies or antibody-containing ascites fluids were diluted to give 50% of the maximum binding to wells of antigen-coated microtiter plates. The % inhibition of binding of the antibody to the antigen by various concentrations of homologous and heterologous haptens at a standard dilution of antibody can then be compared. The advantages of this method of determination of heterocliticity are that it is fast, simple, quantitative and does not need radiolabeled reagents.

Animals↗
PubMed1987

Regulation of murine IgE production in SJA/9 and nude mice. Potentiation of IgE production by recombinant interleukin 4.

Serum IgE levels were determined in different strains of mice with enzyme-linked immunosorbent assay by using rat monoclonal anti-murine IgE antibodies in normal and in Nippostrongylus brasiliensis-infected mice. After infection, serum IgE levels were high in BALB/c and CB-20, low in SJL/J and SJA/20 mice, and not detected at all in SJA/9 and nude mice. Surface IgE-positive cells were greatly increased in BALB/c and SJL/J mice after infection, but not in SJA/9 and nude mice. Most surface IgE-positive spleen cells were also surface IgM- and surface IgD-positive. When spleen cells from SJA/9 or nude mice were stimulated in vitro with lipopolysaccharide and recombinant interleukin 4 (formerly B cell-stimulating factor 1), IgE was produced and detected in the supernatants of these cultures. In addition, surface IgE-positive cells could be detected in these cultures. Most of the surface IgE-positive cells were surface IgM- and surface IgD-negative, unlike those seen in the spleens of Nippostrongylus-infected BALB/c and SJL/J mice. These observations show that SJA/9 and nude mice have IgE-producing precursor B cells, and after appropriate stimulation interleukin 4 can induce them to secrete IgE.

Animals↗
PubMed1987

Antitumor activity and mechanism of action of 6-thio-3-deazaguanine.

6-Thio-3-deazaguanine (TDG), a relatively new purine antimetabolite, exhibits significant antitumor activity against a variety of experimental animal tumor models including C3H mammary adenocarcinoma, Lewis lung carcinoma, adenocarcinoma 755, and leukemias L1210 and P388. However, the drug was ineffective against 3-deazaguanine-resistant L1210 (both in vitro and in vivo) and CEM cells (in vitro). The resistant cells appear to lack HGPRTase activity because the extracts from these cell lines failed to convert hypoxanthine to IMP. These data indicate that TDG needs to be activated by hypoxanthine guanine phosphoribosyltransferase prior to its growth inhibitory effects. Cytotoxicity of TDG was completely reversed by hypoxanthine and inosine. TDG inhibited the synthesis of DNA and RNA equally and effectively, whereas the inhibition of protein synthesis required a prolonged drug exposure and appears to be a consequence of the inhibition of DNA and RNA synthesis. Data from these studies suggest that TDG is an effective antitumor agent, and its spectrum of antitumor activity and mechanism of action appears to be different from that of 3-deazaguanine.

Animals↗
PubMed1987

Immunological and haematological changes during high-dose immunoglobulin therapy in an infant with autoimmune neutropenia.

High-dose immunoglobulin (HD-Ig) therapy was given to an infant with autoimmune neutropenia (AIN), and antineutrophil autoantibodies (ANAA). The patient's absolute neutrophil count in peripheral blood increased from 300/mm3 to 3000-4000/mm3 7 days after treatment. Although the neutrophil count gradually decreased thereafter, transient increases were observed after each single booster infusion repeated at 3-week intervals. By continuing this treatment, clinical symptoms were markedly alleviated, and the patient's susceptibility to infection was reduced. The increase in neutrophils showed a positive correlation with the increase in serum IgG, and with the increase in the ratio of the T helper/T suppressor cells. The neutrophil-bound IgG level and serum lysozyme level were decreased after HD-Ig therapy.

Agranulocytosis↗
PubMed1987

Study of insulin response to oral glucose load after acute and chronic glycemic control in type 2 diabetic subjects.

To investigate whether correction of fasting hyperglycemia per se improves the insulin secretion in type 2 diabetic subjects, plasma insulin response to 75 g oral glucose load has been studied after acute and chronic normalization of fasting plasma glucose levels in 7 overt type 2 diabetic subjects. For the acute normalization of elevated fasting plasma glucose levels, an artificial endocrine pancreas was employed. Although fasting plasma glucose concentrations were normalized before the oral glucose challenge, insulin response to oral glucose was not improved compared to those without normalization of fasting plasma glucose levels. After 1-3 month control of hyperglycemia, the insulin response to glucose in the subjects was significantly improved compared to those without treatments. Results indicate that chronic metabolic control is essential for the improvement of insulin response to glucose in type 2 diabetic subjects, and also suggest that the impaired insulin secretion in type 2 diabetes is not due to hyperglycemia per se, but due to the metabolic derangements which lead to chronic hyperglycemia.

Adult↗
PubMed1987

Studies on immunity in hybridoma-bearing mice. A. Immune response to antigens. II. inhibition of production of anti-dinitrophenyl antibodies in mice which have rejected the B 53 anti-dinitrophenyl-producing IgE hybridoma.

When BALB/c mice, which had rejected the anti-dinitrophenyl (DNP) IgE-producing hybridoma B 53, were immunized with DNP proteins, they produced much less anti-DNP antibodies than control (normal) mice. The anti-DNP plaque-forming cell (PFC) number was much less when spleen cells from mice immunized with DNP proteins were treated with sera of mice which had rejected the hybridoma B 53 than the PFC number from the same spleen cells not treated by the sera. The sera of mice which had rejected the hybridoma B 53 contained an inhibitor which was adsorbed and eluted from an anti-mouse immunoglobulin column and also a mouse anti-DNP IgG2a column. The inhibition of PFC was hapten-reversible. In Western blotting the eluates from the anti-DNP IgG2a column reacted as well with the blotted anti-DNP IgE B 53 as an anti-idiotypic antibody to anti-DNP IgE B 53. These criteria establish that the inhibitor in the sera of the mice which had rejected the B 53 tumor was an anti-idiotypic antibody of the type which mimics the epitope (DNP) of the immunizing antigen.

Animals↗
PubMed1987

Anti-idiotypic antibody as a mirror image of the paratope of the original antibody.

Immunization with 2,4-dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) produced antibodies with combining sites (paratope) which could accommodate not only the 2,4,6-trinitrophenyl (TNP) antigen but also the 4-hydroxy-3-nitrophenyl (NP) and 4-hydroxy-5-iodo-3-nitrophenyl (NIP) antigens, while immunization with NIP-KLH or TNP-KLH produced antibodies with combining sites which could accommodate only the homologous antigens. Utilizing these cross-reacting anti-hapten antibodies mentioned above, an anti-idiotypic antibody was investigated and characterized. Anti-DNP antibodies (Ab1) cross-reacted with the epitopes TNP, NP or NIP. It was also shown that heterologous anti-anti-DNP antibodies (Ab2) recognized not only the antibody which was produced by immunization with DNP-KLH, but also the antibodies produced by immunization with NIP-KLH, NP-KLH or TNP-KLH. The guinea pig anti-idiotypic antibody which we obtained using murine anti-DNP antibodies (Ab1) as antigen is therefore better defined not as an internal image of the antigen but as a mirror image of the paratope of the immunizing Ab1.

Animals↗
PubMed1987

Computerized glucose clamp method for the determination of insulin sensitivity in diabetic subjects.

A new, simplified computerized glucose clamp method was performed for estimation of glucose utilization at the insulin level of postprandial level. The program for the method is based on the mathematical algorithm using values of blood glucose, changes of its concentration and the desired glucose level. The coefficients of variation of the clamped blood glucose values during the last 60 minutes was 6.3 +/- 1.7(%) in normal, 3.7 +/- 0.3(%) in NIDDM, which was within satisfactory limit, and also indicated an attainment of steady state. Glucose infusion curves showed some bumps for the initial 60 min, which did not seriously affect the glucose utilization rate at steady state. In some cases, whose insulin sensitivity was high, CV was not low enough and occasional manual adjustment of K values was required. Average glucose infusion rate was 7.59 +/- 0.85 (mg/kg/min) in normal, and this was significantly lowered in NIDDM (42.3 +/- 3.4) at steady state, indicating a decreased insulin sensitivity for glucose utilization in NIDDM.

Adult↗
PubMed1987

Hairy cell leukemia in Japanese patients: a study with monoclonal antibodies.

Using a panel of monoclonal antibodies and three anti-hairy cell sera (alpha HC1 and alpha HC2 of Posnett and 4B122 prepared by the authors), hairy cells were phenotyped on frozen sections of cell pellets from blood and spleen of 11 Japanese patients with hairy cell leukemia (HCL). The results were quite similar to those reported for HCL of non-Japanese patients inasmuch as hairy cells in the majority of these patients were B1+, B2-, FMC7+, and IL-2R1+. However, they were more often than not J5+, Leu-1+, alpha HC1-, alpha HC2-, and 4B122+ in contrast to the pattern reported for non-Japanese patients. In conclusion, HCL in the Japanese constitutes a special variant of HCL because of its rareness, unusual immunophenotype, and atypical clinicohematologic features.

Aged↗
PubMed1987

Evaluation of antitumor activity of 1-beta-D-arabinofuranosyl-2-amino-1,4(2H)-4-iminopyrimidine in murine tumors.

1-beta-D-Arabinofuranosyl-2-amino-1,4(2H)-4-iminopyrimidine (ara-AIPy), a new deaminase-resistant analog of cytarabine, exhibited extremely potent antitumor activity against P388 leukemia [400 mg/kg on Days 1-5; increase in life span (ILS), 211%] and significant inhibition against Lewis lung carcinoma (inhibition of tumor weight, 68%) and mammary adenocarcinoma 755 (inhibition of tumor weight, 82%). Schedule-dependency studies indicate that this drug, unlike cytarabine, was effective irrespective of its treatment schedules. The drug exhibited therapeutic efficacy against established P388 tumor transplants (400 mg/kg on Days 3-7; ILS, 131%) and inhibited the tumor growth effectively even when administered as a single dose on Day 1 by both ip (2000 mg/kg; ILS, 150%) and iv (500 mg/kg; ILS, 68%) routes. Ara-AIPy was most effective when administered on Days 1, 3, 5, 7, and 9 after tumor transplantation (400 mg/kg; ILS, 210%, with 50% of animals 60-day survivors). Ara-AIPy inhibited the growth of L1210 leukemia when both the tumor transplantation and the drug treatment were administered by iv route (500 mg/kg on Days 1, 5, and 9; ILS, 181%). The routes of administration of ara-AIPy experiments showed that the drug was effective by both ip and iv routes of administration; however, better therapeutic values were obtained by ip schedules. These studies demonstrate that ara-AIPy exhibits highly significant and broad-spectrum antitumor activity against a variety of experimental animal tumor models and suggest a possible future role for this drug in the treatment of human neoplasia.

Adenocarcinoma↗
PubMed1986

Therapeutic potentials of pretazettine, standard anticancer drugs, and combinations on subcutaneously implanted Lewis lung carcinoma.

We reported previously that pretazettine hydrochloride (PTZ), a narcissus alkaloid, was found to be active against intraperitoneally implanted Lewis lung carcinoma. The therapeutic effectiveness of PTZ has now been investigated on the subcutaneously implanted Lewis lung carcinoma (LLC) which is a representative tumor, resistant to chemotherapy in mice. In syngeneic mice, PTZ therapy was inhibitory to the pulmonary metastasis although it was not effective on prolonging the life span of mice nor inhibitory to the growth of primary tumor implanted on the back of the mice. In allogeneic DBA/2 mice, PTZ was inhibitory to the pulmonary metastasis and also prolonged the life span. In allogeneic BALB/c mice, PTZ increased the number of tumor-free survivors. In syngeneic mice, combination of PTZ with standard cytotoxic drugs such as adriamycin, cis-diamminedichloroplatinum, 5-fluorouracil, methotrexate, or vincristine was found to be active against the subcutaneously implanted LLC. These agents were not effective when administered individually. The activity of cyclophosphamide was increased by a combination with PTZ. The combination of PTZ plus 6-thioguanine was not active. Standard cytotoxic drugs, except methotrexate and 6-thioguanine, were found to be active against subcutaneously implanted LLC in allogeneic DBA/2 mice (not in syngeneic mice) when administered individually. PTZ was also found to be active against subcutaneously implanted LLC in the tails in syngeneic mice on prolonging the life span.

Alkaloids↗
PubMed1986

Protective effect of partially purified human urinary colony-stimulating factor on granulocytopenia after antitumor chemotherapy.

We conducted a randomized crossover study comparing the hemopoietic effect of partially purified human urinary colony-stimulating factor (CSF-HU, an active drug) and human serum albumin (HSA, a control drug) in 24 patients with malignant lymphoma, solid tumors, or multiple myeloma who were receiving two consecutive courses of the same chemotherapeutic regimen. Patients received daily 2-4 X 10(6) units of CSF-HU or an equal amount of protein HSA for five days after the end of the courses of chemotherapy. Assignment to CSF-HU or HSA was determined by the envelope method. The average number of blood granulocytes of 24 cases on day 7 after chemotherapy was 2116 +/- 1649 in CSF-HU-infused courses, which was significantly higher than in HSA-infused courses (1520 +/- 1022) (p less than 0.05). The average time that patients had fewer than 2000 granulocytes/mm3 was 7.6 +/- 4.4 days in CSF-HU-infused courses and 10.3 +/- 5.0 days in HSA-infused courses (p less than 0.02). Fever greater than 38 degrees C was the most frequent side effect, occurring in 32% of the patients receiving CSF-HU infusions. A reduction in the neutropenic interval in CSF-HU-infused courses was observed in patients with fever, as well as in those without fever. Infusions of CSF-HU did not change the number of other hematological parameters, such as erythrocytes, platelets, monocytes, and lymphocytes. These results suggest that CSF-HU infusions may partially protect the patients from granulocytopenia after anticancer chemotherapy.

Agranulocytosis↗