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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 955 records · Page 53Linked to original sources

Radioimmunoscintigraphy of xenografted human thyroid carcinoma.

We developed monoclonal antibodies against human thyroid cancer-associated antigen by fusing mouse myeloma cells with mouse spleen cells immunized by insoluble fraction of homogenized thyroid papillary carcinoma cells. One monoclonal antibody (KTC-3, IgM) was selected to evaluate basic usefulness for radioimmunoscintigraphy in xenografted human thyroid carcinoma. KTC-3 was labeled with 131I by Iodogen method of 20 to 1 Iodogen to IgM molar ratio. It was also labeled with 111In by cyclic DTPA anhydride method of 20 to 1 DTPA to IgM molar ratio. The labeling efficiency and specific activity for 131I labeling were 16.5% and 0.66 mCi/mg IgM respectively, and those for 111In labeling were 12.7% and 1.6 mCi/mg IgM. Imaging and biodistribution of labeled KTC-3 were evaluated in nude mice bearing thyroid anaplastic carcinoma (THC-5-JCK). The tumors were well visualized 3 and 5 days after injection of 131I KTC-3. Tumor uptake of 131I KTC-3 on day 7 was 0.52 +/- 0.27% ID/g and tumor to blood ratio was 1.98 +/- 0.76 (n = 6). Those of 111In KTC-3 were 0.88 +/- 0.09% ID/g and 5.51 +/- 3.36 (n = 6). In conclusion, KTC-3 is promising for radioimmunoscintigraphy of thyroid cancer.

Animals↗

IgE antibody-forming cells in rats infected with Nippostrongylus brasiliensis and immunized with antigens.

The distribution of IgE antibody-forming cells was examined in rats infected with Nippostrongylus brasiliensis (Nb) or immunized with Nb antigen or with OA. The frequency of antigen-specific IgE antibody-forming cells was detected by a passive cutaneous anaphylactic (PCA) reaction using cell extract from lymphoid organs. In Nb-infected rats, anti-Nb and anti-4th stage larvae (L4) IgE-forming cells distributed mainly in the mesenteric and the bronchial lymph nodes (LN) near the parasite-harboring sites. After intraperitoneal (ip) immunization with Nb antigen mixed with Al(OH)3 and Bordetella pertussis (Bp) as adjuvants, anti-Nb IgE antibody-forming cells were detected in the mesenteric and the bronchial LN. Anti-Nb or OA IgE antibody-forming cells after subcutaneous (sc) immunization were found in the inguinal and the axillary LN. An effect of Bp on the distribution of IgE antibody-forming cells seems to be ruled out. The distribution of IgG2a antibody-forming cells was similar to that of IgE antibody-forming cells, indicating that the distribution of the IgE antibody-forming cells is not preferential. IgE antibody-forming cells were stimulated in the regional LN near the site of antigen administration. IgE antibody-forming cells induced by potentiated IgE antibody production were also examined. Rats were immunized ip or sc with OA and infected with Nb. Anti-OA IgE antibody-forming cells were found in all of the lymphoid organs and especially in the regional LN near the Nb parasite-harboring and antigen administration sites.

Adjuvants, Immunologic↗

Dual effects of histamine on spontaneous activity in isolated bovine mesenteric lymphatics.

The mode of action of histamine on spontaneous contractions is isolated bovine mesenteric lymphatics was investigated by recording isometric tensions. Histamine at lower concentrations between about 5 x 10(-8) and 10(-6) M caused a dose-dependent deceleration of the rhythm of spontaneous contractions. Higher concentrations of histamine (more than about 5 x 10(-6) M) produced a dose-related acceleration of the rhythm in association with a slight elevation of basal tone in 115 of 173 preparations. In 58 of 173 lymphatic preparations, histamine at concentrations ranging from about 5 x 10(-8) to 10(-5) M caused only the positive chronotropic effect. The histamine-induced positive and negative chronotropic effects were unaltered by pretreatment with alpha- and beta-adrenergic antagonists but were dose-dependently antagonized by pretreatment with H1- or H2-blockers (diphenhydramine or cimetidine). The specific H1- and H2-agonists, 2-pyridylethylamine (2PEA) and dimaprit caused dose-related positive and negative chronotropic effects, respectively, on spontaneous contractions of isolated bovine mesenteric lymphatics. The effect of 2PEA was significantly blocked by pretreatment with 10(-6) M diphenhydramine, whereas the effect of dimaprit was suppressed by 10(-6) M cimetidine. These results suggest that both H1- and H2-receptors are located on the plasma membrane of smooth muscle cells in bovine mesenteric lymphatics, and that the excitations of H1- and H2-receptors respectively produce an acceleration and a deceleration of the rhythm of spontaneous contractions in lymphatic smooth muscles.

Animals↗

Immunohistochemical identification of type I procollagen in tumour cells of scirrhous adenocarcinoma of the stomach.

Human gastric carcinomas were tested for their immunohistochemical reactivity with anti-type I procollagen antiserum. In all specimens of scirrhous carcinomas, staining of the tumour cells was strongly positive, while in medullary carcinomas staining of the tumour cells was generally poor. These results suggest that the tumour cells in scirrhous carcinomas produce collagen in their stroma.

Adenocarcinoma, Scirrhous↗

Protective immunity and eosinophilia in IgE-deficient SJA/9 mice infected with Nippostrongylus brasiliensis and Trichinella spiralis.

To elucidate the roles of IgE antibody in host responses to helminth infection, selective IgE-deficient SJA/9 mice were infected with the nematode parasites Nippostrongylus brasiliensis, which elicits remarkable potentiated IgE production, and Trichinella spiralis, which induces strong anti-Trichinella IgE antibody production in normal mice. The kinetics of blood eosinophilia, worm burden after primary infection, and resistance to secondary infection in SJA/9 mice were the same in both infections as those in congenic SJL/J mice used as an IgE-producing control. These results indicate that the host responses examined here operate under IgE-independent mechanisms.

Animals↗

Adenosine deaminase attenuates canine coronary vasodilatation during regional non-ischaemic myocardial hypoxia.

To test the hypothesis that adenosine contributes to the coronary hyperaemia produced by regional non-ischaemic myocardial hypoxia coronary blood flow and myocardial oxygen extraction and consumption were continuously monitored in 21 anaesthetised open chest dogs under the following conditions: control 1--postinstrumentation, steady state control; hypoxia 1--3-5 min of regional (LAD) hypoxaemia (partial pressure of oxygen, PO2, 21.4(2.0) mmHg (3.1(0.2) kPa), coronary arterial oxygen content, CaO2, 3.9(0.4) ml.100 ml-1 (39(4) ml.litre-1): control 2--repeat steady state control; and hypoxia 2--3-5 min repeat regional hypoxaemia (PO2 18.9(2.4) mmHg (2.5(0.3) kPa); CaO2 3.6(0.6) ml.100 ml-1 (36(6) ml.litre-1) blood). Left anterior descending artery perfusion pressure was held constant for all conditions. Control 2 and hypoxia 2 were performed in the presence of locally infused adenosine deaminase (n = 16) or saline vehicle (n = 5). The 16 dogs given adenosine deaminase were further subdivided into those perfused with blood deoxygenated by a donor canine lung (group 1, n = 11) and those perfused with blood from a paediatric oxygenator (group 2, n = 5). Systemic haemodynamics, heart rate, and coronary arterial PO2 and O2 contents were similar during the two control periods and during the two exposures to hypoxia in all three groups. Left anterior descending artery blood flow increased by approximately 400% (p less than 0.05) in all three groups during the first exposure to hypoxia. Myocardial oxygen consumption was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Dominant role of circulating catecholamines in the myocardial contractile response to intravenous nicotine.

Experiments were conducted in anesthetized dogs to determine the mechanism primarily responsible for the increase in myocardial contractile function during intravenous infusion of nicotine. Myocardial function was assessed regionally by measuring segment shortening using ultrasonic dimension gauges. The role of cardiac neural stimulation in the absence of direct effects of nicotine and other circulating factors was evaluated by perfusing a region of left ventricular myocardium with blood from a reservoir during systemic nicotine infusion. Segment shortening increased from 11 to 19% in normally perfused myocardium but deteriorated to nearly 0% in reservoir-perfused myocardium. To evaluate direct effects of nicotine on cardiac function, nicotine was infused directly into a perfused coronary artery. An intracoronary concentration of nicotine equivalent to that caused by intravenous administration (0.69 +/- 0.08 micrograms/ml plasma) had no effect on myocardial contractile function. An intracoronary nicotine concentration of 5 micrograms/ml was required to directly increase contractile function to approximately the same extent observed during intravenous nicotine. To evaluate the role of circulating catecholamines in the myocardial response to intravenous nicotine, observations were made before and after bilateral adrenalectomy. Adrenalectomy markedly attenuated the pressor response to intravenous nicotine and abolished the positive cardiac inotropic response. We conclude that the adrenal release of catecholamines is primarily responsible for increased myocardial contractile function during intravenous nicotine.

Adrenalectomy↗

Successful treatment of a VIPoma by continuous subcutaneous infusion of somatostatin analogue (SMS 201-995).

A case with WDHA syndrome due to VIPoma is reported. Injection of somatostatin analogue SMS 201-995 was followed by prompt suppression of vasoactive intestinal polypeptide levels (VIP), decreased stool volume, and restoration of the serum potassium concentration to normal. Long-term treatment with SMS 201-995 for up to 20 weeks produced excellent clinical control and a decrease in tumour size. No adverse effects were noted except for localized pain at the site of injection. This was overcome by using a continuous subcutaneous infusion pump which also enabled the effective daily dosage to be reduced and thereby adverse reactions to be avoided.

Female↗

In vitro evaluation of E1040, a new cephalosporin with potent antipseudomonal activity.

E1040 is a new parenteral cephalosporin with a broad antibacterial spectrum and potent antipseudomonal activity. The compound was four- to eightfold more active than ceftazidime and cefsulodin against Pseudomonas aeruginosa (MIC of E1040 for 90% of strains tested [MIC90], 3.13 micrograms/ml). E1040 also showed a potent activity against other glucose-nonfermentative rods, including Acinetobacter species. The activities of E1040 against most species of the family Enterobacteriaceae were roughly comparable to the activities of ceftazidime and cefmenoxime and exceeded that of cefotiam. Against Citrobacter freundii (MIC90, 0.78 micrograms/ml), Enterobacter cloacae (MIC90, 3.13 micrograms/ml), and Enterobacter aerogenes (MIC90, 0.2 micrograms/ml), E1040 was 16- to 256-fold more active than ceftazidime and cefmenoxime. The activities of E1040 against gram-positive cocci and anaerobes were comparable to those of ceftazidime, but the compound was less active than cefmenoxime. E1040 was at least as resistant as ceftazidime and cefmenoxime to hydrolysis by various beta-lactamases and showed high affinities for penicillin-binding protein 3 of both Escherichia coli and P. aeruginosa.

Bacteria↗

Adenosine deaminase attenuates norepinephrine-induced coronary functional hyperemia.

Responses to norepinephrine (NE) before and after treatment with adenosine deaminase (ADA) were examined in anesthetized dogs. In four dogs repeatable changes in coronary blood flow, myocardial oxygen extraction and consumption, left ventricular +dP/dtmax, and heart rate (HR) were demonstrated during two successive intracoronary infusions of 0.13 micrograms.kg-1.min-1 NE. In eight dogs, the NE-induced hyperemia was decreased from +150 to +67%, the change in myocardial oxygen consumption (MVo2) was attenuated from +177 to +101% by ADA, and the increase in HR was reduced from +28 to +16%. In six dogs, the increase in HR caused by NE before ADA was maintained after ADA by atrial pacing. The NE-induced hyperemia and the increase in MVo2 were again decreased by ADA. Similar results were observed in 12 other dogs with hearts paced at a constant, elevated rate during control as well as during both infusions of NE. In all groups, the O2 extraction response to increased MVo2 increased and the flow response decreased after ADA. In six dogs nitroprusside was infused during NE after ADA. When coronary flow was restored to the same level observed before deaminase, MVo2 was not diminished. These results support a role for adenosine in the coronary functional hyperemia accompanying NE activation of the canine myocardium.

Adenosine↗

Sensitivity of passive cutaneous anaphylaxis in rats. II. Suppression of passive cutaneous anaphylactic reactions in rats infected with Nippostrongylus brasiliensis.

The sensitivity of passive cutaneous anaphylactic (PCA) reaction was examined in rats infected with the nematode parasite, Nippostrongylus brasiliensis (Nb). PCA reactions with anti-DNP IgE antibody were remarkably suppressed by Nb infection already 10 days after infection and persisted for at least 28 weeks. 10 days after infection, no anti-Nb IgE antibody was present in the sera of infected rats, whereas 18 or 28 weeks after infection, circulating anti-Nb IgE antibody was present. It was concluded that two different mechanisms might explain the suppression. 10 days after infection, nonspecific IgE induced by potentiated IgE production inhibited passive sensitization with anti-DNP IgE antibody by occupying the IgE receptors on mast cells, whereas 18 or 28 weeks after infection, the mast cell IgE receptors were occupied by IgE antibody specific for the Nb antigen. The reactivity through non-immunological processes (skin sensitivity to compound 48/80) was not modified by Nb infection at any time after infection.

Animals↗

Comparison of guinea pig IgE antibodies estimated by ELISA with those estimated by passive cutaneous anaphylaxis.

Guinea pig IgE antibodies to ovalbumin or mite were measured by enzyme-linked immunosorbent assay (ELISA), and the levels of IgE antibodies to mite were compared with titers of passive cutaneous anaphylaxis (PCA). The results of ELISA were highly reproducible when the assays were done in the same microtiter plate and on the same day. The levels of IgE antibodies to mite determined by ELISA correlated well with the PCA titers (n = 29, r = 0.70, p less than 0.001). The measurement of IgE antibodies by ELISA saved much time in comparison with PCA which needs at least 7 days for getting results.

Animals↗

Transmural variation in autoregulation of right ventricular blood flow.

We examined transmurally the right coronary autoregulatory flow response to varied perfusion pressures in 11 anesthetized, open-chest dogs. Right coronary artery flow was measured electromagnetically, and its transmural distribution was defined with 15-micron radioactive microspheres. Heart rate, mean aortic blood pressure, right ventricular systolic pressure, end-diastolic pressure, and dP/dtmax were constant. At 100 mm Hg, subepicardial flow averaged 0.48 +/- 0.04 ml/min/g, and subendocardial flow averaged 0.56 +/- 0.05 ml/min/g. In contrast to the left coronary circulation, right coronary hypotension did not cause preferential subendocardial ischemia. As right coronary perfusion pressure was decreased from 100 to 40 mm Hg in five dogs, subepicardial and subendocardial flows were reduced similarly by 35-36%. As right coronary perfusion pressure was elevated from 100 to 150 mm Hg in six dogs, right ventricular subepicardial blood flow increased by 31%, whereas subendocardial blood flow increased by 70%. Right ventricular subendocardial-to-subepicardial flow ratios averaged 1.15-1.20 for perfusion pressures of 40 to 120 mm Hg, and they increased to 1.36 +/- 0.05 at 150 mm Hg. Right coronary artery autoregulatory closed-loop gain averaged 0.47 +/- 0.06 between 70 and 100 mm Hg and was greater than zero from 40 to 120 mm Hg. Between 120 and 150 mm Hg, gain fell to -0.15 +/- 0.10. Regional gain varied from 0.59 +/- 0.10 to 0.44 +/- 0.08 in subepicardium as pressure was decreased from 100 to 40 mm Hg. Subendocardial gains were similar to subepicardial gains over this pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Elevated immunoreactive-somatostatin levels in the brain of ataxic mutant mice].

Immunoreactive-somatostatin (IR-SRIF) levels were investigated in the brain of 4 types of ataxic mice (Rolling Mouse Nagoya, Weaver, PCD, Staggerer) with different cerebellar pathologies. IR-SRIF concentrations (ng/mg) were found to be significantly elevated in both cerebellum and cerebrum of all ataxic mutant mice, IR-SRIF (ng/organ) was found to be increased in the cerebellum and cerebrum in Rolling Mouse Nagoya and PCD compared with control mice. The gel-filtration profile (Sephadex G-50) in the cerebellar extracts of Rolling Mouse Nagoya proved to be identical to that of control mice. Three peaks of IR-SRIF were found to be uniformly elevated in Rolling Mouse Nagoya, with the highest peak coinciding with authentic somatostatin-14. The present results suggest that elevated levels of IR-SRIF in the brain may play a role in the mechanism underlying the manifestation of ataxia in ataxic mutant mice, especially in Rolling Mouse Nagoya and PCD.

Animals↗