Biomedical subjects
Publications and source records attributed to M Hatori.
Streptomyces amphibiosporus R310-104 (ATCC 53964) produced a novel antibiotic lactimidomycin which showed inhibitory activity against fungi and prolonged the survival time of mice transplanted with experimental tumors. Structural studies clarified that lactimidomycin is a new glutarimide antibiotic having a unique unsaturated 12-membered lactone ring.
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Streptomyces cucumerosporus strain L703-4 (ATCC 53784) produces a new 4-methyl-3-hydroxyanthraniloylpentapeptide lactone for which we have proposed the name protactin, in addition to several actinomycin components. Protactin is rather resistant to air oxidation but it can be converted to a new actinomycin, actinomycin Zp by ferricyanide oxidation. Actinomycin Zp possesses in vitro antibacterial activity and in vivo antitumor activity against P-388 leukemia in mice.
In a multicenter clinical trial, the efficacy and usefulness of the BPAA Patch in the treatment of extremity trauma were evaluated in 64 patients and the safety was tested in 70 patients. In 89.1% of the patients studied, the final overall improvement was rated "moderate" or better, and no adverse reactions were reported. The results of this study indicate that the BPAA Patch is a highly useful topical antiinflammatory-analgesic agent for use in the treatment of pain and inflammatory symptoms following trauma.
The usefulness of prostatic specific antigen (PA) was compared with that of prostatic acid phosphatase (PAP). PA was determined in the serum of 2,183 patient examined by the mass screening for prostate cancer from 1987 to 1990. The serum samples of these patients were obtained from our serum bank. PA was measured by the E test "TOSOH" II (PA). The relationship of PA and PAP to prostate size estimated by digital rectal examination (DRE) and ultrasound tomography (US), and age was investigated. PA and PAP correlated with aging and prostate size estimated by DRE. However PA was more apparently related with these things. The correlation between PA and prostatic size estimated by US was relatively high (r = 0.53), but the correlation between PAP and prostate size estimated by US was low (r = 0.20). When the upper limit of normal range was set at 6.0 ng/ml, the sensitivity, specificity and efficiency was 64%, 97% and 62%, respectively. PA was more sensitive than PAP and could be more useful since none of the patients with prostate cancer was PAP positive and PA negative. We conclude that PA should be a reliable tumor marker in our mass screening system.
Melanostatin, a new antibiotic with melanin synthesis inhibitor activity, was isolated from the fermentation broth of Streptomyces clavifer No. N924-2. Its structure was determined by spectral analysis and degradation experiments. Melanostatin strongly inhibited melanin formation in Streptomyces bikiniensis NRRL B-1049 and B16 melanoma cells.
We described a transient low or non-selective proteinuria after forced lordosis as a characteristic of orthostatic proteinuria and the heteroporous theory and sieving function theory which might explain the mechanism of orthostatic proteinuria. The angiogenic action of the renin-angiotensin system played an important part in these theories. Angiotensin II was recognized as the key regulator of renal sodium excretion, because it reduced the urinary Na/K ratio. Since the purpose of this study is to investigate the influence of the renin-angiotensin system on the mechanism of orthostatic proteinuria, proteins and electrolytes in the urine were examined before and after lordosis in 9 healthy children (Group A) and in 6 children with orthostatic proteinuria (Group B). The urinary ratio of protein/creatinine (P/cre) in Group B was already significantly higher than that in Group A before lordosis and significantly increased after lordosis, while P/cre in group A did not increase after lordosis. The urinary Na/K ratio (Na/K) in Group B was already significantly lower than that in Group A before lordosis, and after forced lordosis, Na/K in Group A decrease with no difference between both groups observed. It is suggested that a significant increase on P/cre after lordosis was obtained only in Group A, whereas in both groups the renal vein may be compressed by forced lordosis and as a result angiotensin II may be stimulated. There might be a difference of the responsibility to angiotensin II in glomerular mesangium contraction between both groups.
Pradimicin FA-1 was produced via directed biosynthesis with substitution of D-serine for D-alanine in the 15-position of pradimicin A. This substitution was achieved by the addition of D-serine to the culture medium of Actinomadura hibisca P157-2. Likewise, pradimicin FA-2 was co-produced along with pradimicin FA-1 when the pradimicins A and C producing strain, A. hibisca A2493 was grown in D-serine-supplemented medium. The new pradimicin analogs share a common core structure of 5,6-dihydrobenzo[a]naphthacenequinone substituted by D-serine at C-15, but differ in the disaccharide moiety at C-5. Pradimicin FA-1 has an N-methylamino sugar and D-xylose. Pradimicin FA-2 is the des-N-methyl analog of pradimicin FA-1. The in vitro and in vivo antifungal activity of the analogs was comparable to that of pradimicin A.
New antifungal antibiotics pradimicins D and E were isolated from the culture filtrates of Actinomadura hibisca P157-2 (ATCC 53557) and its mutant A2660 (ATCC 53762). The structure of pradimicin D is N-[[(5S,6S)-5-O-[4,6-dideoxy-4-(methylamino)-3-O-(beta-D- xylopyranosyl)-beta-D-galactopyranosyl]-5,6,8,13-tetrahydro-1,6,9,14- tetrahydroxy-11-methoxy-3-methyl-8,13-dioxobenzo[a]naphthacen++ +-2-yl] carbonyl]glycine, based on spectral analyses compared to pradimicin A. Pradimicin E is the des-N-methyl analog of pradimicin D. Pradimicins D and E were equal in activity to pradimicin A in vitro against a variety of fungi and in vivo against Candida albicans A9540 in mice.
Streptomyces hygroscopicus No. P247-71(ATCC 53709)produced a novel antibiotic eponemycin which exhibited specific in vivo antitumor effect against B16 melanoma. Structural studies assigned (4S)-1,2-epoxy-2-hydroxymethyl-4-(N-isooctanoyl-L- serylamino)-6-methylhept-6-ene-3-one to eponemycin which is unrelated to the known antitumor antibiotics.
The study was carried out on 1466 subjects, whose ages ranged from 20 to 80 years of age, of whom 1181 were dentulous and 285 were complete dentures. We studied the frequency with which the 1466 cases partook of food. The results were as follows: 1) Ingested foods were classified into 10 groups along with the frequency with which they were ingested on a yearly seasonal basis. Food groups were classified as follows: vegetables, grain, sea food, beans, meat, seaweed, potatoes, fruits, etc. 2) The Ingested foods of the dentulous group were similar to those of the complete denture wearers. 3) In all age groups the foods most ingested were: steamed rice, wakame, tofu, bread, scallions, Japanese omelette, and tomatoes. 4) The younger subjects (20 to 39 years) statistically ate significantly lower amounts of steamed rice than did the older age groups. 5) The younger generation ate more meat, while the older groups ate more sea food.
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Bunazosin hydrochloride was administrated in 3-mg oral doses to the 10 patients (6 males and 4 females, average 49.9 years) with dilated cardiomyopathy (DCM) of class II in the NYHA functional classification. Then we observed the changes in their hemodynamics at rest, chest X-ray, echocardiography, humoral factors and symptom-limited exercise tolerance with treadmill testing before treatment and 4 and 8 weeks after administration. All but the left ventricular end-diastolic diameter after 8 weeks were unchanged. Of the humoral factors, only aldosterone decreased significantly during the treatment. On the other hand, the duration of symptom-limited exercise was prolonged significantly, and for a given exercise load, a reduction of heart rate and systolic blood pressure as well as a drop in the PRP occurred at 8 weeks after administration. Therefore, bunazosin appears to improve cardiac function and exercise tolerance in the patients with DCM, at dosages which do not affect hemodynamics at rest.
Bunazosin hydrochloride (Detantol) was administrated in 3-mg oral doses to 10 patients (6 males and 4 females, average 49.9 years) with dilated cardiomyopathy (DCM) of class II in the NYHA functional classification. The patients were observed for changes in their hemodynamics at rest, chest X-ray, echocardiography, humoral factors and symptom-limited exercise tolerance with treadmill testing before treatment and 4 and 8 weeks after administration. All but the left ventricular end-diastolic diameter after 8 weeks were unchanged. Of the humoral factors, only aldosterone decreased significantly during the treatment. On the other hand, the duration of symptom-limited exercise was prolonged significantly, and for a given exercise load, a reduction of heart rate and systolic blood pressure as well as a drop in the pressure-rate product occurred at 8 weeks after administration. Therefore, bunazosin appears to improve cardiac function and exercise tolerance in the patients with DCM, at dosages which do not affect hemodynamics at rest.
Polyangium brachysporum sp. nov. strain ATCC 53080 produces a novel type of antifungal and antitumor antibiotic complex, glidobactins A, B and C. Enhanced production of minor components, glidobactins B and C, was achieved by medium modification. The addition of soybean oil or corn oil, which are rich in unsaturated C18 fatty acids, to the fermentation medium led to an increased production of components B and C. Productivity of component C was selectively enhanced by the addition of oleic acid-rich oils, olive oil and Tween 80 (polyoxyethylene sorbitan mono-oleate). Furthermore, precursing palmitoleate, linoleate and oleate permitted the direct biosynthesis of components A, B and C, respectively. The fermentation with 3% addition of an appropriate oil at initial time provided an optimal production of component B or C.
A new antitumor antibiotic BMY-28438 was isolated from the cultured broth of Streptomyces tropolofaciens No. K611-97. The antibiotic showed potent cytotoxicity against cultured B16 melanoma cells and remarkable prolongation of life span of mice bearing B16 melanoma. The structure of BMY-28438 was determined as 3,7-dihydroxytropolone on the basis of spectral analyses and direct comparison with the authentic compound synthesized.
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An aminoglycoside hypersensitive mutant, Kp-126, was isolated from the aminoglycoside-resistant strain, Kp-8, of Klebsiella pneumoniae through selection using sorbistin, a non-aminocyclitol-aminoglycoside antibiotic. The mutant Kp-126 was approximately 100-fold more sensitive to sorbistin than the parent strain Kp-8. The mutant also showed hypersensitivity to various aminocyclitol-aminoglycoside antibiotics. K. pneumoniae Kp-126 was used in screening and a new aminoglycoside antibiotic, 3,3'-neotrehalosadiamine (BMY-28251), was discovered in the fermentation broths of soil isolate strain of Bacillus pumilus.