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Biomedical subjects

M Hosono

Publications and source records attributed to M Hosono.

At least 91 records · Page 5Linked to original sources
PubMed1995

Radioimmunodetection of human leukemia with anti-interleukin-2 receptor antibody in severe combined immunodeficiency mice.

Anti-Tac monoclonal antibody recognizes human interleukin-2 receptor, which is overexpressed in leukemic cells of most adult T-cell leukemia (ATL) patients. To examine the potency of anti-Tac for targeting of ATL, biodistributions of intravenously administered 125I- and 111In-labeled anti-Tac were examined in severe combined immunodeficiency (SCID) mice inoculated with ATL cells. Significant amounts of radiolabeled anti-Tac were found in the spleen and thymus. The trafficking of ATL cells in SCID mice was detected using 111In-oxine-labeled ATL cells. These results were coincident with the histologically confirmed infiltration of ATL cells. The radiolabeled anti-Tac seemed potent for targeting of ATL.

Adult↗
PubMed1995

Diagnostic value of Tc-99m (V) DMSA for chondrogenic tumors with positive Tc-99m HMDP uptake on bone scintigraphy.

Technetium-99m (V) DMSA scintigraphy was performed in 17 patients with 37 chondrogenic tumors (13 osteochondromas, 14 enchondromas, and 10 chondrosarcomas) that had previously shown uptake of Tc-99m HMDP. Technetium-99m (V) DMSA showed high uptake by all chrondrosarcomas, but low or no uptake always indicated benign chondrogenic tumors. Technetium-99m (V) DMSA scintigraphy may be superior to Tc-99m HMDP scintigraphy for distinguishing benign and malignant chondrogenic tumors, and could also be useful for diagnosing the malignant transformation of chondrogenic tumors.

Bone Neoplasms↗
PubMed1995

Comparison of the chase effects of avidin, streptavidin, neutravidin, and avidin-ferritin on a radiolabeled biotinylated anti-tumor monoclonal antibody.

Injection of avidin can decrease the background radioactivity due to a radiolabeled biotinylated monoclonal antibody. We compared the chase effects of avidin, streptavidin, neutravidin, and avidin-conjugated ferritin on a radiolabeled antitumor monoclonal antibody in tumor-bearing nude mice. A radioiodine-labeled biotinylated monoclonal antibody (OST7) was administered to athymic mice bearing osteogenic sarcomas. After 24 h, an avidin, streptavidin, neutravidin or avidin-conjugated ferritin chaser was intravenously injected into the mice. At 2 h after the chase, the biodistribution of the radiolabeled monoclonal antibody was determined. Clearance from the blood was dose-dependently accelerated by avidin and its effect was 10-fold stronger than that of neutravidin or avidin-ferritin. Streptavidin did not promote clearance of the biotinylated antibody. Avidin was the most effective chasing agent for improving the biodistribution of the radiolabeled biotinylated monoclonal antibody among the four avidin derivatives tested.

Animals↗
PubMed1995

Detection of homing, proliferation, and infiltration sites of adult T cell leukemia cells in severe combined immunodeficiency mice using radiometric techniques.

To clarify the mechanism of in vivo proliferation of adult T cell leukemia (ATL) cells, we examined the organ distribution of ATL-43T cell line cells derived from original leukemic cells in severe combined immunodeficiency (SCID) mice using radiometric techniques. First, we injected 111In-oxine-labeled ATL-43T cells into SCID and CB17 mice. On day 6, significant accumulation of radioactivity was found in the spleen and thymus of SCID mice (33.3 +/- 9.4 and 10.0 +/- 3.6% injected dose/g of tissue [%ID/g], respectively) in comparison with that in CB17 mice (19.1 +/- 2.5 and 3.7 +/- 0.9%ID/g, respectively). Next, we injected radiolabeled anti-Tac monoclonal antibody (MoAb) recognizing human interleukin-2 receptor (IL-2R) alpha chain or isotype-matched control MoAb RPC5 in SCID mice bearing ATL-43T cells 4 weeks after cell inoculation. The amounts of radioactivity found in the spleen and thymus of SCID mice injected with 125I-labeled anti-Tac MoAb (22.5 +/- 6.9 and 22.8 +/- 9.6 %ID/g, respectively) were significantly higher than those in the corresponding organs of SCID mice injected with 125I-labeled RPC5 MoAb (12.0 +/- 5.1 and 7.5 +/- 4.6 %ID/g, respectively). Similar results were obtained with 111In-labeled anti-Tac MoAb. These results were consistent with the histological findings of SCID mice bearing ATL-43T cells, indicating that ATL-43T cells infiltrated preferentially into the lymphoid organs, such as the spleen and thymus, and proliferated there. Thus, the radiometric techniques employed in this study were very useful to evaluate the proliferation sites of ATL-43T cells in SCID mice. Furthermore, this murine model could give us an opportunity to test the feasibility of therapeutic application of radiolabeled anti-Tac MoAb.

Animals↗
PubMed1995

Bronchodilator and cardiovascular effects of NKH477, a novel water-soluble forskolin derivative, in guinea pigs.

The bronchodilator and cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride) were evaluated. In anesthetized guinea pigs, i.v. bolus injections of NKH477 (1-100 micrograms/kg) inhibited the bronchoconstriction induced by inhaled leukotriene D4, increased the heart rate (HR) and decreased the diastolic arterial blood pressure (DBP) in a dose-dependent manner. The bronchodilator effect of NKH477 was 1500 times more potent than that of aminophylline and 17 times less potent than that of isoproterenol. The selectivity of NKH477 for bronchodilation vs an increase in HR was 15 times higher than that of isoproterenol and similar to that of aminophylline; and vs a decrease in DBP, the selectivity was 4 times higher than that of aminophylline and similar to that of isoproterenol. I.v. infusion of NKH477 (0.1-3 micrograms/kg/min) for 2 hr dose-dependently inhibited the bronchoconstriction induced by i.v. histamine. Isoproterenol (0.1 microgram/kg/min, i.v.) enhanced the bronchoconstriction after termination of the infusion, whereas NKH477 did not. In conscious guinea pigs, inhalation of NKH477 (0.1-5 mg/ml) concentration-dependently inhibited the bronchoconstriction induced by inhaled histamine, and a high concentration of NKH477 (35.4 mg/ml) increased the HR. The bronchodilator effect of inhaled NKH477 was 15 times less potent than that of isoproterenol. The selectivity of inhaled NKH477 was similar to that of isoproterenol. These results indicate that NKH477 may be useful as a bronchodilator.

Animals↗
PubMed1995

Inhibitory effect of cilnidipine on pressor response to acute cold stress in spontaneously hypertensive rats.

We investigated the effect of cilnidipine on cardiovascular and neuroendocrine responses to acute cold stress in conscious and unrestrained or moderately restrained spontaneously hypertensive rats (SHRs). Acute cold stress significantly increased mean blood pressure without marked change in heart rate. The acute cold stress-induced elevation in blood pressure was almost abolished by 1 mg/kg, p.o. of prazosin. The cold stress also elevated plasma norepinephrine and epinephrine levels. Cilnidipine at 3 mg/kg, p.o. significantly inhibited the pressor response to acute cold stress. Although 3 mg/kg, p.o. of nifedipine, nicardipine or manidipine lowered mean blood pressure to a similar extent as cilnidipine, none of these three drugs affected the pressor response. Cilnidipine also reduced the cold stress-induced increment in plasma norepinephrine but not the epinephrine level. These findings suggest that acute cold stress may induce the elevation in blood pressure due to an enhanced activation of the sympathoadrenal system in SHRs and that cilnidipine may suppress the pressor response by inhibiting the sympathetic nerve activity.

Animals↗
PubMed1995

Inhibitory effect of cilnidipine on vascular sympathetic neurotransmission and subsequent vasoconstriction in spontaneously hypertensive rats.

We reported previously that cilnidipine inhibited increases in blood pressure and plasma norepinephrine (NE) level in response to cold stress in spontaneously hypertensive rats (SHRs). In the present study, we investigated the effect of cilnidipine on sympathetic neurotransmission and subsequent vasoconstriction in SHRs. In pithed SHRs, electrical sympathetic nerve stimulation (ESNS) elevated blood pressure, and this pressor response was abolished by guanethidine. Cilnidipine at 10 micrograms/kg, i.v. and phentolamine at 1 mg/kg, i.v. suppressed the pressor response to ESNS by 28 +/- 6% and 67 +/- 3%, respectively. Neither nifedipine nor nicardipine inhibited it. The pressor response to exogenous NE was not influenced by cilnidipine. alpha, beta-Methylene ATP inhibited the pressor response to ESNS in the presence or absence of phentolamine. Cilnidipine also attenuated the phentolamine-resistant pressor response to ESNS. In SHR mesenteric vasculatures preloaded with [3H]-NE, cilnidipine (10(-7) M) as well as omega-conotoxin significantly inhibited the 3H overflow evoked by periarterial nerve stimulation. In radioligand binding experiments, cilnidipine inhibited [125I]-omega-conotoxin binding to rat synaptosomes, but it did not inhibit [3H]-prazosin binding to rat cortex membranes. These results suggest that cilnidipine may reduce electrically stimulated NE release from the sympathetic nerve endings of SHR vasculatures probably through its N-type Ca channel blocking action and that cilnidipine may also inhibit the vasoconstriction induced by ATP released concomitantly during nerve stimulation.

Animals↗
PubMed1995

Breakdown of self-tolerance by intrathymic injection of a T-cell line inducing autoimmune gastritis in mice.

Autoimmune gastritis (AIG) develops spontaneously in BALB/c mice thymectomized 3 days after birth (3d-Tx). We first confirmed our previous observations that CD4+ splenic T cells in AIG mice induced AIG in nu/nu mice, while those in normal mice suppressed the development of the disease. In addition, we found that a quantitative balance between these effector (Te) and suppressor (Ts) T cells determined either onset or prevention of the disease. Peripheralization of Ts seemed to begin around 3 days after birth, since the incidence of AIG in mice that underwent Tx 6 days after birth (6d-Tx) decreased markedly, compared with that of 3d-Tx mice; 12% in the former, while 79% in the latter. Notably, Ts existed in the 6d-Tx mice that escaped AIG. We next examined the target specificity of such Ts using syngeneic parietal cells known as autoantigens and two kinds of T-cell lines established from an AIG mouse; one is gastritis inducible in vivo, termed A-II, while another is not, named AC-II. Intrathymic injection of parietal cells into mice 3 days after birth followed by 6d-Tx completely prevented the development of AIG. In contrast, injection of irradiated A-II, but not AC-II cells resulted in AIG in 67% of the mice. No autoimmune oophoritis (AIO) was induced in female mice, implying that the breakdown of tolerance is organ specific. Taken together, peripheral tolerance for organ-specific autoantigens seems to be maintained by CD4+ Ts responding to Te, which induces the disease.

Animals↗
PubMed1994

Inhibition of cell proliferation by Rana catesbeiana and Rana japonica lectins belonging to the ribonuclease superfamily.

Two frog egg lectins [Rana catesbeiana lectin (SBL-C) and Rana japonica lectin] preferentially agglutinate a large variety of human and animal tumor cells but not blood cells, lymphocytes, or fibroblasts. These lectins belong to the superfamily of pyrimidine base-specific RNases. The two lectins bound to a heparin-Sepharose column and were eluted from the column by an increase of NaCl molarity. Both their tumor cell-agglutinating activity and RNase activity were inhibited by heparin, and also by polyamines, such as spermine. Both lectins inhibited P388 leukemia cell proliferation. The inhibitory activity of SBL-C was blocked by addition of heparin. SBL-C inhibited protein synthesis by P388 cells, but RNase A did not. No lectin-induced antiproliferative effect was observed after sialidase treatment of cells. The antiproliferative activity of SBL-C was also inhibited by ammonium chloride treatment. These results suggest that internalization of the lectins by lectin receptor (sialoglycoconjugate)-mediated endocytosis is followed by cell death due to inhibition of protein synthesis. Administration of SBL-C i.p. delayed time to death in mice receiving i.p. transplants of Sarcoma 180 and Mep II cells.

Agglutination↗
PubMed1994

Characterization of a Rana catesbeiana lectin-resistant mutant of leukemia P388 cells.

Sialic acid-binding lectin (SBL-C) from Rana catesbeiana eggs inhibits the growth of tumor cells such as P388 and L1210 leukemia cells (K. Nitta et al., Cancer Res., 54: 920-927, 1994). Here we report the establishment of an SBL-resistant P388 variant cell line, RC-150. Both P388 and RC-150 cells were agglutinated by SBL-C; however, growth of RC-150 cells was unaffected by SBL-C. Cytoplasmic free Ca2+ concentration and transglutaminase activity of RC-150 cells were 0.5 (110 nM) and 3 times (0.62 nmol/mg/min) as high as those of P388 cells, respectively. Microvilli and microplicae were observed on the surface of P388 cells by scanning electron microscopy but were rarely seen on RC-150 cells. Dansylcadaverine-labeled SBL-C bound to both P388 and RC-150 cells. Binding of SBL-C to these tumor cells appears to be mediated by two species of wheat germ agglutinin-stained cell membrane sialoglycoproteins. Labeled SBL-C entered P388 but not RC-150 cells, suggesting that internalized SBL-C acts as an inhibitor of cell proliferation.

Agglutination↗
PubMed1994

Influences of aging and sex on renal pelvic carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice.

Influences of aging and sex on renal pelvic carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined in 6-, 15 -and 45-week-old male and female NON/Shi mice. Histopathological examination revealed an age-related shortening of induction time for renal pelvic carcinomas in males, although actual incidences did not increase. The histological patterns of carcinomas induced in both renal pelvis and urinary bladder demonstrated male mice to be more prone to develop transitional cell carcinomas, while squamous cell carcinomas were more likely to arise in females. Moreover, the sex factor appeared to influence the progression of both renal pelvic and urinary bladder carcinomas.

Aging↗
PubMed1994

Effect of phenacetin pretreatment on renal pelvic carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice of both sexes.

Influences of phenacetin (PH) pretreatment on renal pelvic carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined in NON/Shi mice of both sexes. Histopathological examination revealed that PH pretreatment enhanced not only the induction of urinary tract carcinoma but also distant metastasis of renal pelvic carcinoma by BBN in male mice. The high incidence of urinary tract carcinoma by PH pretreatment might be due to hydronephrosis and epithelial proliferative lesions enhanced by PH, since a single treatment of PH induced hydronephrosis in all mice and simple hyperplasia in 70-80% of mice used.

Animals↗
PubMed1994

Defects of immune cells in the senescence-accelerated mouse: a model for learning and memory deficits in the aged.

We investigated immune characteristics of SAMP8 mice that have early learning and memory deficiencies and a short life span accompanied by normal growth and compared them to those of SAMR1 mice that have a normal aging process. The indexes of immune responsiveness used were natural killer (NK) cell activity, in vitro anti-SRBC (sheep red blood cells) antibody responses, cell proliferation, and interleukin 2 (IL-2)-producing activity in response to concanavalin A of spleen cells. As early as 2 months after birth, SAMP8 mice showed markedly low activity for all the indexes that was not due to a delay of their development. Endogenous NK cell activity in SAMP8 mice remained low or at the background level for a few months, but the trace level of this activity increased after treatment with an immune potentiator of polyinosinic-polycytidylic acid. Because the number of cells bearing an NK cell marker in SAMP8 mice was comparable to that for SAMR1 mice, the low NK cell activity found for SAMP8 mice may not be caused by a low number of precursor cells but by defects in the lytic mechanism or low competence. Flow cytometry analyses showed that the size of the lymphocyte fraction in the spleen is the same for both strains and that T cell fractions, especially of CD4+ T cells in SAMP8 mice are smaller than in SAMR1 mice. In contrast, a B cell fraction was somewhat larger in SAMP8 mice. Together with the fact that the spleen cells of both strains equally stimulated allogeneic T cells in the mixed lymphocyte reaction, the low helper T cell activity in antibody responses, even under the condition of cell-number equivalence, indicates a qualitative defect of CD4+ T cells in SAMP8 mice. This defect probably is closely related to the low endogenous activity of NK cells.

Aging↗
PubMed1994

Dissociation in serum CA125 concentrations measured by different monoclonal antibodies.

The new immunoradiometric assay for CA125 (CA125II assay) uses the monoclonal antibody M11 as an immunoadsorbent. The epitope recognized by M11 is different from the OC125 epitope. Monoclonal antibodies 130-22 and 145-9 recognize an epitope designated as CA130 on the molecule expressing the OC125 epitope. Similarity of M11 epitope to the epitope of anti-CA130 antibodies and dissociation of antigen levels measured by the original CA125 assay and new CA125II assay were examined. Anti-CA130 antibodies partially competed with M11 for the M11 epitope. Among more than 20,000 serum samples we found 12 patients in whom the serum CA125 concentration measured by the CA125II assay was different from that measured by the original assay. In 11 out of 12 patients the CA125 concentration was moderately or extremely high by the original assay but very low by the CA125II assay. Eight of the 11 patients had benign disease, one had no apparent disease and two had cancer. The antigen level determined by CA130 assay was very low in all the 11 patients. In one patient the CA125II assay showed a higher antigen level than the original assay or CA130 assay. The heterogeneity of the epitope expression could cause the dissociation of CA125 levels measured by the different monoclonal antibodies.

Adult↗
PubMed1994

Scintigraphic detection of neural-cell-derived small-cell lung cancer using glioma-specific antibody.

Radiolabeled GA-17, a murine monoclonal antibody that reacts specifically with glioma cells, bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in vivo. The affinity constant of GA-17 F (ab')2 fragment binding to NCI-H69 was 1.02 x 10(8)/M while that to the glioma cell line U87MG was 1.22 x 10(8)/M. Iodine-125-labeled GA-17 F(ab')2 fragments injected i.v. localized well in NCI-H69 cells xenografted in nude mice. The percentage of the injected dose per gram accumulated in the xenografted tumor was 6.87 +/- 1.34% g-1 (mean +/- SD, n = 5) 24 h after injection. On the other hand, control monoclonal F(ab')2 fragments accumulated in the xenografted tumor at 0.75 +/- 0.30% g-1. The tumor-to-blood ratio was 1.8 for NCI-H69, while that of control F(ab')2 was 0.60. In conclusion, the radiolabeled GA-17 F(ab')2 fragment is expected to be useful clinically to visualize the small-cell lung cancer and in radioimmunotherapy.

Animals↗
PubMed1994

131I-metaiodobenzylguanidine therapy for malignant pheochromocytoma.

131I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with malignant pheochromocytoma. The patients received 1-3 doses of 3.33-4.625 GBq (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two patients, the tumor was unchanged in two patients, and slow progression was noted in one patient. Marked improvement in clinical symptoms was achieved in four patients. The other patient had no symptoms before 131I-MIBG treatment, but the serum epinephrine and dopamine decreased. There were no severe untoward responses in four patients. However, one patient developed transient but severe orthostatic hypotension, hypertension, and hyperglycemia from 1 week to 1 month after 131I-MIBG administration. Although complete remission was not obtained, all the patients achieved some benefit from 131I-MIBG therapy. Thus, 131I-MIBG appears to be useful for the palliation of malignant pheochromocytoma.

3-Iodobenzylguanidine↗