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Biomedical subjects

H Sakagami

Publications and source records attributed to H Sakagami.

At least 109 records · Page 6Linked to original sources
PubMed1993

One-shot intravesical instillation of the mucous adhesive anticancer agent hydroxypropylcellulose-doxorubicin for the treatment of superficial bladder carcinoma is sufficient to determine antitumor effects.

A 20 mg/20 ml dose of the membrane adhesive anticancer preparation, hydroxypropylcellulose-doxorubicin (HPC-doxorubicin), was instilled into urinary bladders through a catheter for the treatment of superficial bladder carcinomas (Ta-T1). After 14-30 days, the effects of the drug on tumors was examined by cystoscopy, and the residual tumor tissue where reduction in size was observed was resected by transurethral resection (TUR). Therapeutic effects were as follows: a complete response (CR) was found in 6 cases (37.5%), a reduction in size of more than 50% (partial response = PR) in 4 cases (25%), and a less than 25% reduction (no change = NC) in 6 cases (37.5%). In no case was progression of the disease noted. In CR cases, cold cup punch biopsy revealed no tumor cells remaining at the site where the tumor was present before the instillation. Side effects such as bladder irritation were found in 4 cases, but they were only temporary in nature. The one-dose HPC-doxorubicin approach developed by ourselves allowed detection of antitumor effects between 14 and 30 days after the instillation and therefore determination of sensitivities at an earlier stage than with instillation of the conventional water-soluble type of doxorubicin hydrochloride.

Administration, Intravesical↗
PubMed1993

Lignified materials as medicinal resources. VI. Anti-HIV activity of dehydrogenation polymer of p-coumaric acid, a synthetic lignin, in a quasi-in-vivo assay system as an intermediary step to clinical trials.

After the dehydrogenation polymer of p-coumaric acid, a synthetic lignin, was intravenously injected into mice, the serum was collected immediately, 15 min, 1 h, 5 h, and 24 h after the injection. The serum thus obtained was added to the assay medium containing MT-4 cells infected with HTLV-IIIB (an HIV-1 strain). Inhibition of the cytopathogenicity of HIV by these serum preparations was assayed by the MTT method. The result revealed that lignins could be a promising class of anti-HIV agents with an unidentified unique mode of action.

Antiviral Agents↗
PubMed1993

Administration and dosage of iohexol, a nonionic contrast medium, for dynamic renal computed tomography.

We investigated the optimal method of administering iohexol, which contains 300 mg iodine/ml (Omnipaque 300), a nonionic contrast medium, to maintain adequate renal contrast while reducing artifacts during dynamic CT scanning. In this study, 76 patients with renal disease received 10-50 ml of iohexol as follows: group I (14 patients), 20 ml injected as an intravenous bolus for 5 sec, followed by 30 ml intravenous drip infusion for 5 min; group II (18 patients), bolus of 20 ml injected for 5 sec; group III (13 patients), 20 ml diluted with sterile water (total volume 40 ml), and injected as a bolus for 8 sec; group IV (15 patients), 20 ml injection for 5 sec followed by intravenous drip infusion of 200 ml of Hartmann-Ringer's solution given at maximum speed; and group V (14 patients), 10 ml diluted with sterile water (total volume 20 ml) injected as a bolus for 5 sec. We found that corticomedullary differentiation was most distinct on the images obtained from group IV. We concluded that a lower concentration of iohexol (150 mg iodine/ml) given by intravenous fluid loading can provide superior CT images.

Adult↗
PubMed1992

Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase.

Oligomeric ellagitannins (nobotanins B, E, and K) were found to be potent inhibitors of poly(ADP-ribose) glycohydrolase purified from mouse mammary tumor 34I cells. Kinetic analysis revealed that the inhibition of nobotanin B (dimer) was competitive with respect to the substrate poly(ADP-ribose), whereas nobotanin E (trimer) and nobotanin K (tetramer) exhibited mixed-type inhibition. These results suggest that the dimeric structure of ellagitannin may have a functional domain that competes with poly(ADP-ribose) on the poly(ADP-ribose) glycohydrolase molecule. To determine the inhibitory effects of oligomeric ellagitannins on poly(ADP-ribose) glycohydrolase in vivo, we examined their effects on de-poly(ADP-ribosyl)ation of some chromosomal proteins in intact 34I cells that was induced by glucocorticoid treatment. Nobotanin B caused concentration-dependent inhibition of glucocorticoid-induced de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in intact 34I cells. Interestingly, this inhibition was associated with suppression of the glucocorticoid-sensitive mouse mammary tumor virus (MMTV) mRNA synthesis. In contrast, nobotanin E and K had little inhibitory effect on either de-poly(ADP-ribosyl)ation of these proteins or induction of MMTV transcription after glucocorticoid treatment. Nobotanin B but not E and K was taken into 34I cells. These results may suggest that the suppression of glucocorticoid-sensitive MMTV transcription results from in vivo inhibition of poly(ADP-ribose) glycohydrolase by nobotanin B. These results also indicate the importance of de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in regulation of transcription of the glucocorticoid-sensitive MMTV gene.

Animals↗
PubMed1992

Stimulation of human monocyte and polymorphonuclear cell iodination and interleukin-1 production by epigallocatechin gallate.

(-)Epigallocatechin gallate (EGCg) stimulated iodination of human peripheral blood monocytes, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells, dependent on time, dose, and temperature. However, EGCg did not affect iodination of nonadherent peripheral blood mononuclear cells, red blood cells, or 11 other cultured cell lines. Although various immunoregulators such as lipopolysaccharide (LPS), opsonized zymosan, 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor stimulated PMN iodination to varying degrees, their ability to stimulate monocyte iodination was much lower than that of EGCg. Washout experiments demonstrated that contact with EGCg for less than 60 min irreversibly stimulated PMN and monocyte iodination. EGCg also potently stimulated the production of interleukin-1-like factor by monocytes. The data suggest that EGCg is a strong in vitro stimulant of human phagocytes.

Adjuvants, Immunologic↗
PubMed1992

Inhibition of human immunodeficiency viral replication by tannins and related compounds.

Among 87 chemically defined tannins and related compounds, several hydrolyzable tannins, but not condensed tannins or other lower molecular weight polyphenols, significantly inhibited both the cytopathic effect of human immunodeficiency virus (HIV) and the expression of HIV antigen in human lymphotropic virus type I (HTLV-1)-positive MT-4 cells. The 50% effective concentrations (2.0-4.8 micrograms/ml) of the active compounds were 13- to 15-fold lower than their 50% cytotoxic concentrations. Their anti-HIV activity was demonstrated to be mediated, at least in part, by inhibition of HIV adsorption to the cells.

Adsorption↗
PubMed1992

Localization of gene expression of calreticulin in the brain of adult mouse.

The localization of gene expression of calreticulin, a calcium-binding protein in the endoplasmic reticulum, was examined throughout the entire brain of adult mice by in situ hybridization. Calreticulin mRNA is expressed widely and heterogeneously in discrete neurons throughout the brain, but the white matters expressed it weekly or faintly. In the olfactory bulb, the mRNA is expresses moderately in the mitral cells, but weakly in the periglomerular cells and internal granule cells. In the cerebrum, the gene is expressed intensely in the piriform cortex, but weakly in neocortex, the entorhinal cortex and the amygdaloid nuclei. In the hippocampal formation, calreticulin mRNA is expressed intensely in the CA1-CA3 regions but less intensely in the granule cells of the dentate gyrus. The caudate-putamen, thalamic and hypothalamic nuclei, and mammillary nuclei express the mRNA weakly or faintly. In the mesencephalon, pons and medulla, moderate expression of the mRNA is detected in the pontine nuclei and the locus ceruleus. Weak expression of the mRNA is detected in several discrete nuclei and zones such as the substantia nigra, the superior colliculus and the central gray. Expression signals of calreticulin mRNA are faint in the inferior olive. In the cerebellum, calreticulin mRNA is expressed moderately in the Purkinje cells whereas no significant expression is detected in the granule cells. The plexus choroideus of the lateral, third and fourth ventriculi express calreticulin mRNA intensely although no distinct expression of the mRNA is discerned in the ependyma.

Animals↗
PubMed1992

Gene expression of Ca2+/calmodulin-dependent protein kinase of the cerebellar granule cell type or type IV in the mature and developing rat brain.

The localization and ontogenic changes of expression of the mRNA for Ca2+/calmodulin-dependent protein kinase of the cerebellar granule cell type or type IV (CaM kinase Gr or IV) in the rat brain were examined by in situ hybridization histochemistry. At the young adult stage, intense expression signals for this kinase mRNA were detected in the cerebellar granule cells, the hippocampal pyramidal cells, the dentate granule cells, and the piriform cortex. Moderate levels of the mRNA were expressed in the thalamic nuclei and the cerebral cortex. No distinct expression signals were detected in the Purkinje cells and most brainstem nuclei except for the pontine nuclei, locus ceruleus and inferior olive which showed weak expression. During development, two chronological patterns of changes in the gene expression for this kinase were discerned. The first was a high and persistent expression from the developing stages till the adult stage, which was observed in the cerebellar granule cells, the hippocampal pyramidal cells and the dentate granule cells. The other was a transiently high expression during limited developmental periods, which was observed in the Purkinje cells, neurons in the inferior olive, various brain stem nuclei, and the subventricular neuronal cells. These findings suggest that this Ca2+/calmodulin-dependent protein kinase is involved differentially in multiple Ca2+ signaling pathways in different developing and mature neurons.

Animals↗
PubMed1992

Renal cortical scarring in acute pyelonephritis.

A series of 14 patients with acute pyelonephritis was evaluated for the formation of renal scarring by serial computed tomography (CT) and intravenous urography. Although the urography results were normal, CT showed renal parenchymal atrophy (cortical scarring) in 6 patients. Cortical scarring was observed to occur after 61 to 187 days, and it was slower to develop in the patients with recurrent fever lasting for 2 weeks or more in total than in those with fever for less than 2 weeks. Scarring was significantly more frequent in patients with severe renal involvement than in those with mild involvement, and scars developed at the sites of the most extensive lesions seen on the initial CT scans. Cortical scars were detected in 6 of the 7 patients in whom the lesions occupied 30% or more of the renal parenchyma. We conclude that the extent of the initial renal parenchymal involvement was the most important determinant of eventual scar formation.

Adolescent↗
PubMed1992

Studies on the retention of the mucous-membrane-adhesive anticancer agent hydroxypropylcellulose doxorubicin.

Incorporation of hydroxypropylcellulose (HPC-)doxorubicin, which we developed as a mucous-membrane-adhesive drug preparation, was instilled into the urinary bladder in 10 clinical cases. Tumor of the urinary bladder was a single tumor in all 10 cases, and preclinical histology showed transitional cell carcinoma, grade 1 or 2, and a lower stage than T1. HPC-doxorubicin, 20 mg/20 ml, was administered in 5 cases, and the other 5 cases received the conventional aqueous doxorubicin, 20 mg/20 ml by way of a catheter and the urethra. Cold punch biopsy was performed after 3 days of instillation, and the incorporation of doxorubicin into both tumorous and normal tissue was measured by high-pressure liquid chromatography. After 3 days, it was found that in the HPC-doxorubicin-administered group, doxorubicin was detected in both tumorous and normal tissue, but it was not detected in either tissue after aqueous doxorubicin administration. In 5 cases of the HPC-doxorubicin group, doxorubicin levels in the tumorous and normal tissue were examined, and it was found that significantly more doxorubicin was detected in the tumorous tissues. Thus, it may be said that our HPC-doxorubicin remained longer within the urinary bladder than the conventional aqueous doxorubicin preparation. Instilled HPC-doxorubicin is more highly concentrated in the tumorous tissue than in the normal bladder tissue, and thus, HPC-compounded anticancer drugs may be therapeutically more useful.

Administration, Intravesical↗
PubMed1992

Lignified materials as medicinal resources. V. Anti-HIV (human immunodeficiency virus) activity of some synthetic lignins.

A class of synthetic lignins (dehydrogenation polymers of p-coumaric acid, ferulic acid, and caffeic acid) inhibited cytopathogenicity of HIV-1 and HIV-2 infection. The ratio of cytotoxic to anti-HIV (human immunodeficiency virus) doses depended strongly on conditions during polymer preparation. The activity increased when polymers were treated with reducing agent NaBH4, whereas it decreased when treated with oxidizing agent ceric ammonium nitrate. The polymers inhibited expression of HIV-specific antigen in the infected cells and also inhibited HIV-binding to the cells, but not completely, even at doses that almost completely inhibited the HIV-induced cytopathogenic effect. These results suggest that lignin structure, regardless of whether synthetic or natural, may inhibit HIV replication by an unidentified process, and thus prove to be a new class of anti-HIV agents possibly effective in the treatment of AIDS (acquired immunodeficiency syndrome).

Antiviral Agents↗
PubMed1991

Stimulation of human peripheral blood polymorphonuclear cell iodination by lignin-related substances.

Lignin is a heterogenous natural product composed of phenylpropane units and is usually associated with hemicellulose in its native state. Until now little attention has been paid to the potential therapeutic utility of lignified products. Natural lignified products are demonstrated in the present study to stimulate iodination significantly (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). This stimulation was significantly inhibited in the presence of myeloperoxidase inhibitors. These materials were almost completely deprived of their stimulation capacity by treatment with NaCIO2, but this capacity was not affected by severe treatment with H2SO4 or trifluoroacetic acid. Similar stimulating activity by chemically defined tannin-related polyphenolic compounds was observed. Degradation products or component units of lignin, and natural antitumor polysaccharides and their chemically modified derivatives (introduced with negatively or positively charged groups) and polysialoglycoproteins had little or no activity. The results indicate the importance of a polymerized phenolic structure for the stimulation of PMN iodination. Possible physiological relevance of the stimulation of iodination by lignified substances is discussed.

Antineoplastic Agents↗
PubMed1991

Possible involvement of lignin structure in anti-influenza virus activity.

Commercial lignins suppressed the growth of influenza A virus infecting MDCK cells, and the RNA-dependent RNA synthesis, as efficiently as the high-molecular weight fractions extracted from pine cone of Pinus parviflora Sieb. et Zucc. The anti-influenza A virus activity of both pine cone extract and commercial alkali-lignin was considerably reduced by treatment with sodium chlorite, but was not affected by sulfuric acid or trifluoroacetic acid. The degraded components of lignin, various synthesized polyphenols unrelated to lignin, and natural and chemically modified glucans, were not appreciably inhibitory. The data suggest that the polymerized phenolic structure of lignified materials is responsible for the anti-influenza A virus activity.

Animals↗
PubMed1991

Inhibition of human immunodeficiency virus forward and reverse transcription by PC6, a natural product from cones of pine trees.

We have previously shown that PC6, a natural product extracted from cones of Pinus parviflora Sieb et Zucc, can inhibit the replication of human immunodeficiency virus type 1 (HIV-1) in CD4+ T cells and in monocyte/macrophage cell lines. Here, we show by immunoprecipitation of HIV-1 proteins with a specific pooled serum that PC6 inhibited the expression of all HIV-1 proteins in CEM cells. PC6 did not affect the posttranslational processing of the HIV-1 proteins. Northern, Southern, and kinetics analyses revealed that PC6 inhibited HIV-1 reverse and forward transcription in CEM cells. Transient transfection of CEM cells with HIV-1 long terminal repeat (LTR) linked CAT DNA also showed that PC6 inhibited LTR-driven gene expression at the transcriptional level.

Antiviral Agents↗
PubMed1991

Late phase allergic reaction to a CT contrast medium (iotrolan).

A 46-year-old male developed wide-spread erythema and edema after intravenous injection of a CT contrast medium (iotrolan). The skin eruption appeared at 6 h, reached a maximum at 9 to 12 h, and faded within 36 h after injection. A challenge with an intradermal injection of the agent provoked the same reaction where the eruption had originally appeared, but had no effect on previously unaffected regions. Histopathologic examination revealed a perivascular infiltration of small round cells, and a few neutrophils, and eosinophils in the dermis and focal spongiosis in the epidermis. This is the first report of a late phase allergic skin reaction induced by iotrolan.

Contrast Media↗
PubMed1991

Effect of cacao husk extract on human immunodeficiency virus infection.

A sodium hydroxide extract from cacao husk inhibited the cytopathic effect of human immunodeficiency virus type 1 (HIV-1) against HTLV-1-transformed T-cell lines MT-2 and MT-4. It also inhibited syncytium formation between HIV-infected and uninfected lymphoblastoid T-cell line, MOLT-4. The anti-HIV activity was concentrated by membrane filter fractionation to a fraction with molecular weight of 100-300 KDa. Anti-HIV activity of the extract was attributable to interference with the virus adsorption, rather than to inhibition of the virus replication after adsorption.

Cacao↗