Saburo Koshimura

Inhibition of HIV-reverse transcriptase activity by some phloroglucinol derivatives

Four phloroglucinol derivatives, named mallotophenone (5‐methylene‐bis‐2,6‐dihydroxy‐3‐methyl‐4‐methoxyacetophenone), mallotochromene (8‐acetyl‐5,7‐dihydroxy‐6‐(3‐acetyl‐2,4‐dihydroxy‐5‐methyl‐6‐methoxybenzyl)‐2,2‐dimethylchromene), mallotojaponin (3‐(3,3(dimethylallyl)S‐(3(acetyl‐2,4‐dihydroxy‐5‐methyl‐6‐methoxybenzyl)‐phloracetophenone) and mallotolerin (3‐(3‐methyl‐2‐hydroxybut‐3‐enyl)‐5‐(3‐acetyl‐2,4‐dihydroxy‐5‐methyl‐6‐methoxybenzyl)‐phloracetophenone), have been tested for their ability to inhibit the activity of human immunodeficiency virus (HIV)‐reverse transcriptase. Under the reaction conditions with (rA)n · (dT)12–18 as the template · primer, the enzyme activity was inhibited by approximately 70% in the presence of 10 μ/ml mallotochromene or mallotojaponin, whereas mallotophenone and mallotolerin were much less inhibitory to the enzyme. The enzyme activity was also inhibited, though to lesser extent, by these compounds under similar conditions with initiated MS‐2 phage RNA as the template · primer, The mode of inhibition was, as analyzed with mallotojaponin, competivite with respect to the template · primer, (rA)n · (dT)12–18, and non‐competitive with respect to the triphosphate substrate, dTTP, The K i value of mallotojaponin for HIV‐reverse transcriptase was determined to be 6.1 μM.

Augmentation of various immune reactivities of tumor-bearing hosts with an extract of Cordyceps sinensis

In order to enhance general reactivity of immune system in the tumor-bearing host, we employed extract ofCordyceps sinensis (CSE) as a biological response modifier.Cordyceps sinensis is an interesting material produced by a kind of mushroom parasitic to larval moths and was used to hasten recovery from exhaustion in ancient China.In this experiment, C57BL/6 mice implanted subcutaneously with syngeneic EL-4 lymphoma cells were employed as the host. Oral administration of the extract leads to a reduction of tumor size and prolongation of the host survival time. As judged by plaque-forming cells against T-dependent (sheep erythrocytes) and T-independent (bacterial lipopolysaccharide) antigens, CSE showed to augment the antibody responses. As for the activities of peritoneal macrophages, chemotaxis was dramatically depressed within a few days after EL-4 transplantation up to the end of life, but treatment with CSE at −14, −7, −4, +4, +7 and +10 days after the tumor transplantation augmented the activity about four times stronger than that of control. Phagocytic activity of macrophages was also decreased in tumor-bearing mice treated with cyclophosphamide (100 mg/kg) 3 and 5 days after tumor transplantation. But administration of CSE restored the activity to more than the normal level. The overall efficacy of CSE was tested with protective activity against systemic infection bySalmonella enteritides. The tumor-bearing mice receiving this medicine lived significantly longer than any other groups without CSE.

Phenoxazinone synthesis by human hemoglobin

We found that 2-amino-5-methylphenol was converted to the dihydrophenoxazinone with a reddish brown color by purified human hemoglobin, lysates of human erythrocytes, and human erythrocytes. The reddish brown compound was identified as 2-amino-4,4 alpha-dihydro-4 alpha,7-dimethyl-3H-phenoxazin-3-one by the measurement of NMR spectra, IR spectra, EI mass spectra, and absorption spectra. The changes in this phenoxazinone were studied under various conditions after mixing 2-amino-5-methylphenol with purified oxy- or methemoglobin, or with human erythrocytes. The production of 2-amino-4,4 alpha-dihydro-4 alpha,7-dimethyl-3H-phenoxazine-3-one from 2-amino-5-methylphenol was found to be tightly coupled with the oxidation of ferrous hemoglobin and reduction of ferric hemoglobin under aerobic conditions. By studying the production rates of the dihydrophenoxazinone and the oxido-reduction rates of ferrous and ferric hemoglobins during the reactions of ferrous or ferric hemoglobin with 2-amino-5-methylphenol under aerobic and anaerobic conditions, the reaction mechanism was extensively proposed.

Changes in immunological parameters in lung cancer patients undergoing immunotherapy with streptococcal preparation OK-432

SummaryWe have studied the immunological status of patients treated with streptococcal preparation OK-432. Two KE of OK-432 was injected intramuscularly once every week for more than three years unless the patients died. The natural killer (NK) activity in those patients who underwent curative surgery for lung cancer and had no sign of recurrence was significantly increased (P < 0.01) during the OK-432 treatment. However, the NK activity in the patients who had persistent disease (non-resected cases, incompletely resected cases or recurrent cases) was not significantly increased in comparison with that before the immunotherapy. Also, in the cases with no clinical symptoms of recurrence, both the lymphoblastogenetic reactions to the mitogens and the IL-2 production were significantly enhanced(P < 0.01) during the administration of OK-432. Reactions in the SU-PS (polysaccharide taken from the cell-wall fraction of theStreptococcus pyogenes SU strain and containing 7.2% of protein) skin-test appeared to significantly correlate with the immunological status of the patients under OK-432 therapy, but the PHA and PPD skin reactions showed no definitive enhancement. The survival rate of the patients whose SU-PS skin tests were positive during the OK-432 immunotherapy was significantly higher (P < 0.01) than that of the patients with negative reactions.

Complementary and Alternative Medicine in Japan

In recent years, complementary and alternative medicine (CAM) has grown in popularity worldwide. The World Health Organization (WHO) classifies 65–80% of the world’s health care services as “traditional medicine” 1. Therefore, from the viewpoint of the population ratio, more people use CAM than modern Western medicine.