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Biomedical subjects

M Honda

Publications and source records attributed to M Honda.

At least 577 records · Page 32Linked to original sources

Antiviral potencies of BV-araU and related nucleoside analogues against varicella-zoster virus in different cell lines.

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and nine other antiherpesviral nucleoside analogues were compared for their potencies against four strains of varicella-zoster virus (VZV) on three different cell lines: HEL cells, Vero cells, and MS cells established from a human malignant schwannoma. In contrast to the activity against herpes simplex virus type 1 previously reported, BV-araU showed extremely marked antiviral activity against VZV even on Vero cells. ED50, 50% plaque reduction dose, of BV-araU for VZV was 0.20-3.1 and 0.14-0.63 ng/ml on Vero cells and on HEL cells, respectively. Potency of BV-araU on MS cells was similar to that on these cell lines. There was not significant variation in anti-VZV activities of other nucleoside analogues on these three different cell lines except a few combinations of VZV strain and test compound.

Animals↗

[Diagnosis of varicella-zoster virus (VZV) infection by using FITC-labeled monoclonal antibodies].

Anti-varicella zoster virus (VZV) mouse monoclonal antibodies conjugated with fluorescein isothiocyanate were evaluated for their usefulness as a practical diagnostic tool in the clinical field by examining cells infected with isolated herpes viruses and 431 clinical samples. The kit stained clearly the cells infected with 14 isolated VZV strains without cross reaction to 15 isolated herpes simplex virus type-1 strains (HSV-1) and 14 type-2 (HSV-2) strains. In clinical specimens, viral antigens of VZV were detected in 92/105 (87.6%) cases of varicella and in 176/190 (92.6%) cases of herpes zoster. Specific fluorescence of VZV was also observed in 5 out of 96 cases diagnosed as HSV infections, although these samples had no specific reaction to HSV when tested by the commercially available diagnostic kit. In 24 cases which could not be clinically diagnosed as herpes zoster or herpes simplex, the VZV antigen was demonstrated in 9 cases. All 109 VZV-positive cases in virus isolation by culture were also judged VZV-antigen positive by the kit, while all 69 HSV-positive cases in virus isolation were VZV-antigen negative. Furthermore, the VZV antigen was detected by the kit in 53/60 clinical diagnoses of varicella or herpes zoster without successful virus isolation. These results clearly indicate the usefulness of the kit as a practical VZV diagnostic reagent, especially in terms of specific sensitivity and easy technical manipulation.

Antibodies, Monoclonal↗

Hepatic neoplasms: detection with hepatoportal subtraction angiography--a new technique of DSA.

A new technique for hepatic intraarterial digital subtraction angiography (DSA)--hepatoportal subtraction angiography (HPSA)--that emphasizes the enhancement of tumors by suppressing liver parenchymal enhancement has been developed. The tumor detection sensitivity of HPSA was evaluated prospectively in comparison with that of conventional hepatic intraarterial DSA, unenhanced computed tomography (CT) or CT enhanced with iodine-containing contrast material (conventional CT), CT with iodized oil, and ultrasound (US). For 84 detected lesions of hepatoma, the sensitivity of HPSA was 92%, statistically superior to the 71% of hepatic intraarterial DSA (P less than .002), the 42% of US (P less than .001), and the 39% of conventional CT (P less than .001) and nearly the same as the 90% of CT with iodized oil. Among 33 lesions of metastasis, HPSA depicted 91%; conventional CT, 93%; US, 87%; and hepatic intraarterial DSA, 76%. HPSA was more sensitive than hepatic intraarterial DSA, but the difference was not statistically significant. Compared with hepatic intraarterial DSA, HPSA enabled detection of more faintly enhanced tumors, and this technique was considered useful for detecting small hypervascular hepatic tumors.

Adult↗

Infarction of the conus medullaris.

We encountered a patient with acute cauda equina syndrome. The clinical course, laboratory data and imaging study, including magnetic resonance imaging (MRI) strongly suggested that this episode was caused by a vascular disorder of the conus medullaris. We emphasized the diagnostic usefulness of MRI in the vascular disease of the conus medullaris as well as the clinical importance of this disease in the differential diagnosis of acute cauda equina syndrome.

Aged↗

Synthesis of platinum complexes of 2-aminomethylpyrrolidine derivatives for use as carrier ligands and their antitumor activities.

In order to study a new antitumor platinum complex, various platinum complexes were prepared from 2-amino-methylpyrrolidine derivatives synthesized to serve as carrier ligands and tested for their antitumor activity against Colon 26 carcinoma (s.c.-i.p. system) and P388 leukemia (i.p.-i.p. system) in mice. 2-Aminomethylpyrrolidine proved to be the most effective carrier ligand in its amine derivatives. The structure-activity relationships of the carrier ligands in the platinum complexes with dichloro, oxalato, 1,1-cyclobutanedicarboxylato and dichlorodihydroxo as leaving group were clearly shown on the Colon 26 carcinoma screen and were as follows: the antitumor activity of the platinum complexes with any leaving groups was considerably decreased by the substitution of hydrogen by alkyl group (Me, Et) on nitrogen of aminomethyl and the effects of 1,1-cyclobutanedicarboxylato Pt(II) complexes completely disappeared with the same substitution on nitrogen of pyrrolidine. In all the tested platinum complexes 2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platin um(II) (15) exhibited the most potent antitumor activity. 15 was superior to 1,1-cyclobutanedicarboxylatodiammineplatinum(II) (CBDCA) and similar to cis-diamminedichloroplatinum(II) (CDDP) on the Colon 26 carcinoma screen but it was inferior to CBDCA and CDDP on the P388 leukemia screen. Furthermore, 15 showed more potent antitumor activity than CBDCA against Colon 38 carcinoma (s.c.-i.p. system).

Animals↗

Effects of E-1020, a new cyclic AMP-specific phosphodiesterase inhibitor, on cyclic AMP and cytosolic free calcium of cultured vascular smooth muscle cells.

The purpose of this study is to clarify the pharmacological effects of E-1020 a new cAMP-specific phosphodiesterase (PDE) inhibitor, on cAMP or cytosolic free calcium (Ca) of cultured vascular smooth muscle cells (VSMC). VSMC were separated from the thoracic aorta of 2- to 3-month-old Wistar Kyoto rats (WKY). cAMP was measured by using the 125I-cAMP radioimmunoassay kit. The cytosolic free Ca of VSMC was measured by using the fluorescence Ca indicator, Fura-2/acetoxymethyl ester (Fura-2/AM). As a result, E-1020 increased the cAMP of VSMC in a dose-dependent manner, and about two fold increase in cAMP was observed by 10(-4) M E-1020. E-1020 decreased the cytosolic free concentration of Ca in a dose-dependent manner, and a significant decrease in cytosolic free Ca was observed by greater than 10(-6) M E-1020. These effects of E-1020 on cAMP and cytosolic free Ca were enhanced in the presence of low concentration (10(-8) M) of DL-noradrenaline. That is, a more prominent decrease in cytosolic free Ca than that of E-1020 alone was observed. Our results show that E-1020 decreases cytosolic free Ca of VSMC in parallel with increase in cAMP, and thereby suggest a potential vasodilating activity in vivo.

Animals↗

Adenylate cyclase activities of vascular smooth muscle in early and established DOCA/salt hypertensive rats.

It has been demonstrated that the adenylate cyclase activity of vascular smooth muscle regulates its tonus. The present study was undertaken to examine adenylate cyclase activity in early and established deoxycorticosterone acetate (DOCA)/salt hypertensive rats. Early and established DOCA/salt hypertensive rats were prepared by injecting 30 mg of DOCA weekly for 3 and 10 weeks, respectively, into male Wistar rats given drinking water with 1% saline. The membrane protein fraction medium containing the protein, 50 microM isoproterenol, 100 microM GTP, 50 microM forskolin or 25 microM calmodulin was applied. The adenylate cyclase activity was determined by a modified method developed in our laboratory using double isotope counting. The adenylate cyclase activity in the early DOCA/salt hypertensive rats was significantly higher (p less than 0.05) than that in the control rats in the basal condition, which was unaffected by additions of isoproterenol, GTP or forskolin. There was no significant difference in basal adenylate cyclase activity between the established DOCA/salt hypertensive and control rats. The adenylate cyclase activities in the established DOCA/salt hypertensive rats were significantly lower with GTP (p less than 0.02) and forskolin (p less than 0.01) as compared with the control rats. Calmodulin elevated the adenylate cyclase activity significantly (p less than 0.05) in the established DOCA/salt hypertensive rats as well as in the control rats. However, enzyme activity with calmodulin in the established DOCA/salt hypertensive rats was significantly lower (p less than 0.05) than that in the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

Effect of atrial natriuretic peptide on adrenal renin and aldosterone.

The effect of atrial natriuretic peptide (ANP) on adrenal renin and aldosterone was investigated in anesthetized rats. Under pentobarbital anesthesia 40 mg/kg), intravenous infusion of ANP (0.25 micrograms/kg/min) for 45 min failed to alter the adrenal renin, adrenal aldosterone, and plasma aldosterone (PA). In this condition, intraperitoneal injection of ACTH (10 micrograms/kg) significantly increased the adrenal renin (from 2.4 +/- 0.1 to 5.0 +/- 0.08 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 13.6 +/- 1.3 to 22.7 +/- 2.3 ng/mg protein, P less than 0.01) and PA (from 59.8 +/- 5.8 to 75.5 +/- 7.4 ng/dl, P less than 0.05), respectively. Under ACTH stimulation, ANP infusion induced significant decreases in adrenal renin (from 5.0 +/- 0.08 to 2.8 +/- 0.2 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 22.7 +/- 2.3 to 16.2 +/- 1.8 ng/mg protein, P less than 0.05) and PA (from 75.5 +/- 7.4 to 61.6 +/- 4.9 ng/dl). These results suggest a possible role for adrenal renin in the mechanism underlying the inhibitory effect of ANP on aldosterone production in vivo.

Adrenal Glands↗

Preventive effect of angiotensin I on weight reduction in the adrenal glands of DOCA/salt hypertensive rats.

We examined the effect of angiotensin I (AI), without the effect of angiotensin II (AII) converted from AI, on the weight of the adrenal glands, adrenal corticosterone (B) and adrenal aldosterone under conditions where the renin-angiotensin system was suppressed, since a reduction in the size of the adrenal glands is often observed in DOCA/salt hypertensive rats. Sixty male Wistar rats fed on a 1% NaCl solution were divided into 6 groups as follows: a) Salt group: received sesame oil and vehicle, b) Salt + C group: received sesame oil and MK422 (0.14 mg/day), an angiotensin converting enzyme inhibitor (CEI), c) DOCA group: received DOCA (30 mg/week) and vehicle, d) DOCA + A group: received DOCA and AI (0.5 mg/kg/day), e) DOCA + A + C group: received DOCA and AI with MK422, and f) DOCA + C group: received DOCA and MK422. After 4 weeks, the rats were sacrificed to sample their blood and remove their adrenal glands. There was no significant difference in adrenal B among the groups apart from the DOCA + C group. Adrenal aldosterone was lower in the groups of DOCA/salt hypertensive rats than in the Salt group and Salt + C group. Furthermore, the DOCA + A + C group and DOCA + C group had lower adrenal aldosterone levels than the DOCA group and DOCA + A group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Effect of cytokines on HIV release and IL-2 receptor alpha expression in monocytic cell lines.

A monocytic cell line, THP-1, was acutely infected with HIV, and the effects of various factors including INF-gamma, LPS, IL-2, and IL-6 were analyzed. While IFN-gamma suppressed HIV production, IL-2 and IL-6 augmented it. The suppressive effect of IFN-gamma was not overcome by IL-2 or by LPS. We studied whether the induction of IL-2 receptor alpha (IL-2R alpha) expression by those factors was related to HIV infection or not. By immunofluorescence analysis using monoclonal anti-IL-2R alpha antibody, we observed that HIV infection itself induced IL-2R alpha expression moderately in U937 and THP-1, and IL-6 as well as IFN-gamma highly induced IL-2R alpha expression both in uninfected and infected THP-1. Although induction of HIV production and IL-2R alpha expression by cytokines seem not to be directly correlated, these results suggest that soluble IL-2R alpha increased in AIDS patients might be at least partly derived from infected monocyte/macrophages activated by various cytokines, especially IL-6, which is mainly produced by themselves.

Cell Line↗

[A new ALS scale and prospective study of amyotrophic lateral sclerosis progression].

We developed a new ALS scale which is characterized by inclusion of as many check items as 77 which range from cranial nerve region to extremities and trunk. Despite of large number of items, it is neither time-consuming, nor poses much burden on patients or examiners as the activity tests are so devised and most of them can be done while the patient remains in supine position. In addition, an attempt is made that the total score obtained by the scale reflects not only the degree of disability of the patients but also the extent of motor neuron loss. Using the scale, ALS progression was prospectively studied in 13 patients and it was found that in older patients ALS progresses more rapidly than in younger patients.

Adult↗

The effects of maternal diabetes on placental transfer of essential and non-essential fatty acids in the rat.

Studies were performed on the transfer of essential and non-essential non-esterified fatty acids across the in-situ perfused placenta in normal and diabetic rats in late gestation. Results indicated that increasing maternal glycaemia is associated with a decrease in the unidirectional transfer of both essential and non-essential fatty acids. This reduced transfer is dependent upon the uteroplacental blood flow, which is compromised in the diabetic animals. The transfer of essential fatty acid was always twofold that of non-essential fatty acids regardless of the total amount of lipid transferred, indicating a selective mechanism for the transfer of these moieties.

Animals↗

Elevation of immunoreactive platelet prostaglandin E and plasma prostaglandin F2 alpha in diabetic pregnancy.

Platelet prostaglandin (PG) E and plasma PGF2 alpha concentrations were measured by radioimmunoassay methods and compared in non-pregnant and pregnant, normal and diabetic subjects. The blood samples were obtained in the follicular phase in the non-pregnant women and in the third trimester and after delivery in the pregnant women. The immunoreactive platelet PGE (IRPGE) levels were significantly higher in the pregnant diabetic women than in the normal non-pregnant and pregnant women and diabetic non-pregnant women. The immunoreactive plasma PGF2 alpha (IRPGF2 alpha) concentrations were significantly higher in the non-pregnant diabetic women than in the normal non-pregnant and pregnant women. During pregnancy, the plasma IRPGF2 alpha were further increased significantly in the diabetic subjects compared to the non-pregnant diabetics. Both the platelet IRPGE and plasma IRPGF2 alpha concentrations were higher in the pregnant diabetic subjects with retinopathy than in those without retinopathy. These findings suggest that pregnancy and diabetes influence the synthesis of PGE and PGF2 alpha in the platelets and plasma, respectively. The increased production of these prostaglandins are possible exacerbating factors of diabetic retinopathy during pregnancy.

Adult↗

[Host factors that changes the distribution of immunotoxin].

Mouse monoclonal antibody A 7, which was raised against human colon cancer, was used for preparing the conjugates with neocarzinostatin, mitomycin C and adriamycin. The tissue distribution of these three conjugates were examined in athymic nude mice transplanted with human colon cancer. The distribution in tumor was different in these three conjugates. The route of administration of the conjugate affected its distribution in tumor tissues. In the case of tumor transplanted in the back of mice, intravenous administration seemed to superior to intraperitoneal one. In clinical trials of immunoconjugate composed of A 7 and polypeptide anticancer drug neocarzinostatin (A 7-NCS), human anti-mouse antibody (HAMA) was observed in most cases without serious immune response such as anaphylactic shock. Human antibody against neocarzinostatin could not be detected in any case receiving A 7-NCS.

Animals↗

[Missile therapy of colorectal and pancreatic cancers--clinical trial of monoclonal antibody, A7-NCS, in 73 patients with colorectal and pancreatic cancers].

Monoclonal antibody-drug conjugate, A7-NCS, was applied for 73 patients with colorectal and pancreatic cancer, including metastasis of liver, lung and peritoneum. Monoclonal antibody A7, from a mouse splenocyte immunized against human colon cancer was bound covalently to Neocarzinostatin (NCS), Mitomycin C (MMC) and Adriamycin (ADM) to form A7-NCS, A7-MMC and A7-ADM, respectively. Fifty-four patients with colon cancer, fifteen patients with postoperative liver metastasis of colorectal cancer and one patient with advanced pancreatic cancer were given A7-NCS intra-arterially. Two patients with postoperative lung metastasis of colon cancer were injected intra-venously and one patient with postoperative peritoneal metastasis of colon cancer was given it intraperitoneally. Three patients with liver metastasis showed evidence of tumor reduction on CT scan and three claimed pain relief. Postoperative survival of the patients with distant metastasis exhibited slightly higher survival rate in the patients with A7-NCS, as compared with the patients without A7-NCS. There was no serious adverse effect in the patients given A7-NCS. Human anti-mouse antibody (HAMA) was detected in all patients given the conjugate. Repeated injections of A7-NCS for several consecutive days following the first injection brought about the same A7 pattern as the first injection.

Aged↗

[Immunoresponses and efficacy after arterial infusion of immunoconjugate A7-NCS in patients with colon cancer].

We prepared an immunoconjugate, A7-NCS, of a mouse-derived anti-human colon cancer monoclonal antibody A7 and the macromolecular protein anticancer agent neocarzinostatin (NCS), and evaluated changes in human anti-mouse antibody (HAMA) by ELISA in the serum of patients intraarterially administered this agent. IgG and IgM class HAMA were detected in all patients, but no IgE class HAMA. In patients with stage V disease, the survival rate was higher in a group treated with A7-NCS at an NCS dose of 4,000 units or more than in that treated at an NCS dose of less than 4,000 units. In these patients, the survival rate was higher in a group treated with A7-NCS at an NCS dose of 4,000 units or more than in one not treated with it. These results suggest the usefulness of A7-NCS administration at high dose for prolonging survival of patients with advanced colon cancer.

Animals↗

Three-dimensional observation on sarcoplasmic reticulum and caveolae in myocardium of spontaneously hypertensive rats.

Three-dimensional observation of intracellular membranous structures in myocardium was carried out in spontaneously hypertensive rats (SHR; a model of hypertrophied myocardium) under a scanning electron microscope (SEM) and compared with those of age- and sex-matched normotensive Wistar-Kyoto rats (WKY). There was no apparent difference in the ultrastructures of the myocardium between 5-week-old SHR (before the onset of hypertension but with mild cardiac hypertrophy) and age- and sex-matched control rats. Ten-week-old SHR in an early stage of hypertension with significant cardiac hypertrophy, showed a significant increase in the number of caveolae compared with those of 10-week-old WKY, and numerous abnormal caveolae aggregates connected by filamentous structures. Moreover the density of the network of sarcoplasmic reticulum (SR) was also increased, and some SR had a giant, squamous appearance. Accumulation of mitochondria with dense cristae was also observed in 10-week-old SHR. In 20-week-old SHR with established hypertension and cardiac hypertrophy, the caveolae and SR observed in 10-week-old SHR were no longer present, but caveolae were distributed in bands with variable width, parallel to the long axis of the myocardium. A wavy arrangement of mitochondria, fragmentation and stacks of mitochondrial cristae were observed in 20-week-old SHR. The changes of caveolae and giant squamous SR in cardiac hypertrophy observed in the present study have never been reported in previous studies. Our results suggest that the changes in caveolae, SR and mitochondria observed in SHR may be important morphological signs during development of cardiac hypertrophy in SHR.

Animals↗