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Biomedical subjects

H Sakagami

Publications and source records attributed to H Sakagami.

At least 127 records · Page 7Linked to original sources

Lignified materials as a potential medicinal resource. IV. Dehydrogenation polymers of some phenylpropenoids and their capacity to stimulate polymorphonuclear cell iodination.

Based on our recent finding regarding diverse biological activities of natural lignified materials, synthetic dehydrogenation homo- and copolymers were prepared using 3 p-hydroxylated cinnamic acids and coniferyl alcohol in order to explore the role of lignin skeleton in the activities displayed by natural lignins. The synthetic polymers stimulated polymorphonuclear cell iodination as potently as the natural lignified materials.

Electron Spin Resonance Spectroscopy↗

Effects of chemically defined tannins on poly (ADP-ribose) glycohydrolase activity.

Three classes of chemically defined tannins, gallotannins, ellagitannins and condensed tannins were examined for their inhibitory activities against purified poly (ADP-ribose) glycohydrolase. Ellagitannins showed higher inhibitory activities than gallotannins. In contrast, condensed tannins, which consist of an epicathechin gallate (ECG) oligomer without a glucose core were not appreciably inhibitory. Kinetic analysis revealed that the inhibition of ellagitannins was competitive with respect to the substrate poly(ADP-ribose), whereas gallotannins exhibited mixed-type inhibition. These results suggest that conjugation with glucose of hexahydroxy-diphenoyl (HHDP) group, which is a unique component of ellagitannins, potentiated the inhibitory activity, and that the structure of ellagitannins may have a functional domain which competes with poly(ADP-ribose) on the poly(ADP-ribose) glycohydrolase molecule.

Glycoside Hydrolases↗

[Current status of the conservative treatment of urinary bladder for invasive bladder cancer].

During the 3 years from 1987 to 1990, we gave hyperthermia to 11 of the patients who visited our department for the treatment of invasive bladder cancer. Results and prognosis are reported. Stage and grade of the cancer before the treatment in 11 cases were T2 in 5 cases, T3 in 3 cases, T4 in 3 cases, transitional cell carcinoma (TCC) grade 2 in 8 cases, TCC grade 3 in 2 cases, and TCC grade 3 + anaplastic carcinoma in 1 case. Complications were observed in 8 of the 11 cases, such as severe heart disease and others. Pretreatment of radiation therapy, transurethral resection or chemotherapy was given in all cases. Hyperthermia was performed combined with hydroxypropyl cellulose-(HPC)-adriamycin, or radiation therapy, and the following results were obtained: complete response (CR) in 4 cases, partial response (PR) in 4 cases, no change (NC) in 2 cases and progressive disease (PD) in 1 case. Among 4 cases of PR, total cystectomy was performed in 3 cases. These 3 cases and the 4 cases of CR are alive now, but the other 4 patients died.

Carcinoma↗

Anti-influenza virus activity of synthetically polymerized phenylpropenoids.

Various dehydrogenation polymers (the so-called synthetic lignins) were synthesized from four different phenylpropenoids by endwise and bulk polymerizations and investigated for their anti-influenza virus activity. All of these materials suppressed the plaque formation of influenza virus infecting MDCK cells and the RNA-dependent RNA synthesis as effectively as the high molecular weight lignin-related extract (Fr. VI) of pine cone of Pinus parviflora Sieb. et Zucc. The structural simplicity and higher solubility of the synthesized polymers suggest that they might be regarded as potential candidates for medicinal antiviral resources.

Antiviral Agents↗

Inhibition of influenza virus infection by pine cone antitumor substances.

The anti-influenza virus activity of polysaccharides and other high molecular weight fractions from pine cone extract (PCE) of Pinus parviflora Sieb. et Zucc. was investigated. None of the fractions affected the growth of MDCK cells. The acidic PCE substances markedly suppressed the growth of the influenza virus in MDCK cells. Significant inhibition of both the viral protein synthesis in infected cells and virion-associated RNA-dependent RNA polymerase activity was observed with these acidic fractions. Although amantadine inhibited virus plaque formation as effectively as PCE fractions, it was less effective in inhibiting the RNA polymerase activity. These results suggest that PCE, which has been shown to contain antitumor substance(s), also contains anti-influenza virus substance(s).

Amantadine↗

Computerized tomography in acute pyelonephritis: the clinical correlations.

Computerized tomography was performed on 19 patients diagnosed as having uncomplicated acute pyelonephritis. The relationship was investigated among the laboratory findings, presence of flank pain, clinical course and severity of the lesions detected by computerized tomography. In patients febrile for less than 2 weeks healing as assessed by computerized tomography took an average of 76 days. However, in patients with repeated febrile episodes occurring for longer than 2 weeks healing was delayed until an average 232 days after onset. Computerized tomography findings generally correlated well with the erythrocyte sedimentation rate, C-reactive protein level, and presence of pyuria and flank pain. However, in patients with a prolonged course computerized tomography proved to be a more reliable indicator of progress than either the results of laboratory tests or the symptoms. In conclusion, computerized tomography was useful in the diagnosis, assessment of severity and evaluation of healing of acute pyelonephritis.

Blood Sedimentation↗

Modification of human immunodeficiency viral replication by pine cone extracts.

We have shown previously that two fractions (PC6 and PC7) extracted from cones of the Japanese white pine Pinus parvifloria Sieb. et Zucc have potent immunopotentiating effects. Here, we show that PC6 and PC7 inhibited HIV-1 replication (greater than 95%), in a dose-dependent manner, in chronically infected CR10/HIV-1 cells and in acute cytolytic HIV-1 infection of CEM cells. Treatment of CEM cells, prior to or after acute infection with HIV-1, reduced subsequent viral production, but the best inhibitory effect was obtained with treatment before and after infection: an 80% inhibition was achieved with as little as 3 micrograms/ml of PC6. Comparable results were also obtained when PC6 was used to inhibit HIV-1 replication in the U937 human histiocytic lymphoma cell line. Both PC6 and PC7 were relatively nontoxic to cells. The anti-HIV-1 effect of PC6 and PC7 we observed in this report, coupled with earlier reports of their immunopotentiating properties suggest their potential as ideal therapeutic agents for the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗

Lignified materials as potential medicinal resources. III. Diversity of biological activity and possible molecular species involved.

Diverse biological activities of hot-water and alkali extracts of lignified materials were reviewed and the molecular species involved are discussed. Materials tested included pine cone of Pinus parviflora SIEB. et Zucc., wood chips of slash pine, Douglas fir, and tallow wood, and two basidiocarps, in addition to their partially degraded preparations and commercial lignins. As a tentative conclusion, the lignin structure of these extracts might be responsible for the potent stimulation of granulocytic cell iodination, inhibition of viral infection and/or proliferation in vitro, and inactivation of viral ribonucleic acid (RNA)-dependent RNA polymerase and (adenosine diphosphate-ribose)n glycohydrolase. Other activities displayed by some of these extracts, such as antibacterial and antitumor activities, induction of hemolytic plaque-forming-cells in mice, and stimulation of deoxyribonucleic acid synthesis of isolated splenocytes, remain to be investigated.

Animals↗

[A combined treatment with 8 MHz radiofrequency hyperthermia, HPC-adriamycin, immunotherapy, radiation, systemic chemotherapy and irradiation for invasive bladder carcinoma].

Hyperthermia was induced for the treatment of invasive bladder carcinoma in order to study its usefulness. The subjects were 12 cases of invasive bladder cancer; including 5 cases of T2, 3 cases of T3, 2 cases of T4, and 2 cases of recurrence after total cystectomy. As previous treatment, 4 patients received radiotherapy and the other received TUR, systemic chemotherapy, and intravesical injection of anticancer drugs. For hyperthermia treatment, a Thermotron RF-8 was used for heating a deep seated tumor. Each case received hyperthermia 2 to 10 times. Combined therapy included injection of HPC-adriamycin into the urinary bladder in 5 cases, immunotherapy in 3 cases, M-VAC therapy in one case, radiotherapy in one case, radiotherapy and intra-arterial injection in one case, and Peplomycin and OK-432 local injection in one case. The treatment results showed a 75% effectiveness; with CR in 4 cases, PR in 5 cases, MR in 2 cases and PD in one case. Three patients died and 9 survived. Of four patients who had received radiotherapy as a previous treatment 3 cases obtained CR and one case MR. Therefore, it was considered that a favorable treatment effect with hyperthermia could be obtained after radiotherapy.

Aged↗

Decrease in asparagine synthetase activity during cell differentiation of mouse and human leukemia cell lines.

The activity of asparagine synthetase decreased almost 50% during dexamethasone-induced mouse myeloid leukemia M1 cell differentiation. This enzyme activity also declined significantly during differentiation of the human myelogenous leukemic cell lines, HL-60 and U-937, induced by either macrophage culture supernatant or retinoic acid. The decline of asparagine synthetase activity closely paralleled the expression of various maturation markers, but could also be induced by serum starvation. These results suggest that asparagine synthetase or L-asparagine has some biological function in growth regulation of these leukemia cell lines.

Animals↗

[Clinical effects of hyperthermia treatment for recurrent bladder cancer].

The usefulness of the application of thermotherapy for cases of recurrent bladder cancer was investigated. We encountered 7 cases of which intravesical recurrent bladder cancer was found to occur in 5 cases. The involvement of the lymph node was found in one case and recurrence in intrapelvic cavity was observed in another case after total cystectomy. As a treatment method, thermotherapy was applied for the above 5 cases between 2 and 7 times in conjunction with an intrabladder injection of hydroxy propyl cellulose-adriamycin following M-VAC treatment for one case; the combined use of OK 432 and 5Fu was administered for another case together with thermotherapy applied 4 to 5 times, respectively. Results; Three of the above 5 cases were found to be CR including 2 cases of PR. One case was MR with another case of NC. Shrinkage of the tumor by more than 50% was recognized in one case of NC after five months.

Adult↗

Stimulation of tumor necrosis factor-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction.

The mouse macrophage-like cell line, J774.1, spontaneously released differentiation-inducing factor(s). When these cells were treated with a protein-bound polysaccharide, PSK, significantly higher amounts of differentiation-inducing activity were accumulated in the culture supernatant. PSK directly stimulated human myelogenous leukemic cell differentiation induced by J774.1 conditioned medium or by tumor necrosis factor. Among four subfractions of PSK, only the highest molecular weight fraction (MW greater than 200 kD) exerted such a stimulating effect.

Animals↗

Stimulation of granulocytic cell iodination by pine cone antitumor substances.

Antitumor substances (Fractions VI and VII) prepared from the NaOH extract of pine cone significantly stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood adherent mononuclear cells, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells. In contrast, these fractions did not significantly increase the iodination of nonadherent mononuclear cells, red blood cells, other human leukemic cell lines (U-937, THP-1, K-562), human diploid fibroblast (UT20Lu), or mouse cell lines (L-929, J774.1). Iodination of HL-60 cells, which were induced to differentiate by treatment with either retinoic acid or tumor necrosis factor, were stimulated less than untreated cells. The stimulation of iodination of both PMN and HL-60 cells required the continuous presence of these fractions and was almost completely abolished by the presence of myeloperoxidase inhibitors. The stimulation activity of these fractions was generally higher than that of various other immunopotentiators. Possible mechanisms of extract stimulation of myeloperoxidase-containing cell iodination are discussed.

Adjuvants, Immunologic↗

[A study on accumulation of cholesterol in rat prostate].

An experimental model of prostatic hypertrophy was created by freezing the urethra at the opening of the ventral prostate in rats and administering a cholesterol-rich diet to induce cholesterol accumulation. Four-week-old Fisher rats were divided into a control group, a cholesterol-rich diet group (by adding 1% cholesterol to the diet), a frozen group, and a frozen and cholesterol-rich diet group, and were reared for 5 months. The animals were killed, and the ventral prostate was removed, weighed, and the lipid was extracted. Cholesterol content was measured by an enzymatic method. A cholesterol-rich diet without freezing had no effects on the ventral prostate, and after freezing alone, the weight of the prostate was smaller than that of the control group. However, in the group cholesterol-rich diet after urethral freezing, the cholesterol content per mg of tissue increased. This indicates that cholesterol accumulation can be induced in the prostate by administering a cholesterol-rich diet after creating the proper secretory disturbance.

Animals↗

Lignin inhibits (ADP-ribose)n glycohydrolase activity.

(ADP-ribose)n glycohydrolase activity was inhibited in vitro by lignin, a naturally occurring polymethoxyphenolic compound. However, coniferyl alcohol, which is a main component of lignin, was not inhibitory even at 100 micrograms/ml. Lignin caused competitive inhibition with respect to the substrate (ADP-ribose)n and its Ki value was 18 micrograms/ml. These results suggest that lignin with a polymerized structure has a functional domain that interacts with the (ADP-ribose)n glycohydrolase molecule at the same site as (ADP-ribose)n.

Binding, Competitive↗

Inhibitory effect of tannin on poly(ADP-ribose) glycohydrolase from human placenta.

Tannin, a naturally occurring polyphenolic compound, was found to inhibit the activity of purified poly(ADP-ribose) glycohydrolase from human placenta. The inhibition was dose-dependent and half maximal with 2.8 micrograms/ml of tannin. The inhibitory effect of tannin was two and three orders of magnitude more than those of ADP-ribose and cAMP, respectively. Kinetic analysis revealed that the inhibition by tannin was competitive with respect to the substrate poly(ADP-ribose).

Binding Sites↗