Biomedical subjects
Publications and source records attributed to S Nozoe.
Terphenyl compounds, tentatively named Bl-I (1), Bl-II (2), Bl-III (3), Bl-IV (4) and Bl-V (5), showing 5-lipoxygenase inhibitory activity have been isolated from the mushroom Boletopsis leucomelas (Pers.) Fayod. On the basis of physico-chemical and spectral evidence, they were concluded to be a series of cycloleucomelone-leucoacetates.
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2' -Deoxymugineic acid (DMA), one of mugineic acid-family phytosiderophores (MAs), was synthesized in vitro both from l-methionine and from nicotianamine (NA) with a cell-free system derived from root tips of iron-deficient barley (Hordeum vulgare L.). The reactions producing DMA from NA needed an amino group acceptor (i.e. 2-oxoglutarate, pyruvate, or oxalacetic acid) and a reductant (i.e. NADH or NADPH). The activity of the enzymes to produce NA from l-methionine was the highest at about pH 9. This biosynthetic activity was markedly induced by iron-deficiency stress. The synthesis of NA from S-adenosyl-l-methionine was more efficient than from l-methionine. From the results with the cell-free system reported here, we propose a revised biosynthetic pathway of MAs.
The aporphine alkaloids, dicentrine, glaucine, corydine, and apomorphine were shown to have inhibitory activity against several mouse tumor cell lines, leukemia P388 and L1210, melanoma B16, bladder cancer MBC2, and colon cancer Colon 26 in culture. These aporphine alkaloids also inhibited the mitogen-induced lymphocyte proliferation as well as the growth of IL-2 dependent CTLL2 line in a dose-dependent way. Of the four alkaloids apomorphine proved to be most potent in the inhibitory action. Apomorphine treatment resulted in some prolongation of survival time of the mice inoculated i.p. with P388, although its activity was not enough to meet the standard criterion for antitumor activity.
Three bisbenzylisoqinoline alkaloids, chondocurine (Chon), berbamine (Ber), and cycleanine (Cyc) were tested for their protective effect on the quick death of mice primed with bacillus Calmette Guerin (BCG) and elicited with lipopolysaccharide (LPS). Seven-consecutive treatments with Chon or Cyc at a dose of 10 mg/kg following BCG priming resulted in significant improvement in the survival rate. A single dose of Chon also protected the BCG/LPS-treated mice from death if it was given immediately after, not 4 h after, LPS elicitation. These data show that bisbenzylisoquinoline alkaloids can protect mice from the lethal toxicity induced by the BCG/LPS combination treatment by inhibiting the priming with BCG or the elicitation with LPS.
To clarify the physical and mental symptoms of long-lasting anorexia nervosa (AN), we chose and examined 16 cases suffering from the disease for 10 years or more, among 138 cases admitted to our hospital with AN from 1972 to 1988. These prolonged cases almost changed into bulimic types and had various forms of abnormal eating behavior and physical symptoms. Frequency of abnormal eating behavior, other forms of abnormal behavior, physical and psychotic symptoms such as fear, were higher in the prolonged cases than in cases suffering for less than 3 years. In these prolonged cases, irreversible and life-threatening symptoms were especially common. Finally most of them experienced social withdrawal.
Three new fasciculol esters, fasciculic acids A (1), B (2) and C (3), having potent calmodulin antagonistic activity were isolated from the toxic mushroom Naematoloma fasciculare (Fr.) Karst. Their structures were elucidated on the basis of spectral and chemical evidence.
Analogues of glutamic acid were synthesized and evaluated for their inhibitory activity toward glutamine synthetase (EC 6.3.1.2; GS). The title compound, 4-N-hydroxy-L-2,4-diaminobutyric acid (NH-DABA), showed a potent inhibitory activity against GS from both sheep brain and soybean. The inhibition is competitive with respect to glutamic acid and the Ki values of sheep brain GS and soybean GS for NH-DABA are 0.007 mmol and 0.021 mmol, respectively. The activity of inhibition is comparable to those of L-methionine sulfoximine and 2-amino-4-(hydroxymethyl-phosphinyl)butyric acid (phosphinothricin).
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Five indolealkylamines (N,N-dimethyltryptamine, N-methyltryptamine, bufotenine, O-methylbufotenine, N,N,N-trimethyltryptamine iodide) were labeled with 11C by use of 11CH3I. The labeled compounds were synthesized with a radiochemical yield of 2-50% (based on trapped 11CH3I) in 20-35 min with radiochemical purities of more than 92%. The tissue distributions of these labeled compounds were investigated in rats. In all cases, the accumulations in the liver, lung and small intestine were high. [11C]DMT and [11C]OMB also accumulated to a large extent in the brain, where their accumulation was retained. Brain uptake of three other radiopharmaceuticals was low. [11C]DMT is the radiopharmaceutical of choice for the study of the serotonin action mechanism in the brain, because it has the highest radiochemical yield and the highest brain uptake of these 11C-labeled compounds.