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The structures of the antibiotics FR-900098 (II) and FR-33289 (III), isolated from Streptomyces rubellomurius, have been established as 3-(N-acetyl-N-hydroxyamino)-propylphosphonic acid and 3-(N-acetyl-N-hydroxyamino)-2 (R)-hydroxypropylphosphonic acid, respectively, on the basis of spectroscopic and chemical evidence and, finally, by synthesis.

Various compounds related to the hypocholesterolemic alkaloid eritadenine (I) were synthesized for the evaluation of structure-activity relationships in this series. 6-Sub-stituted purine analogs were prepared by reacting the 6-chloro-purine intermediate (II) with the corresponding nucleophilic reagents. 2, 6-Di-substituted purine derivatives were prepared by utilizing a route involving an imidazole ring closure step, starting from the appropriately substituted pyrimidine precursors and the amino-acid (VI). The preparation of 6, 8-di-substituted purine analogs was achieved by cyclization of the 5-amino-pyrimidine intermediate (XXIX) derived for the synthesis of I.

The synthesis three stereoisomers of eritadenine (I) ; D-threo-(II), L-threo-(III) and L-eritadenine (IV), described. D-threo-Eritadenine (II) was derived from eritadenine by utilizing a novel ■thro-threo epimerization. L-threo-Eritadenine (II) was synthesized, starting from L-threonolactone dibenzoate (IX), through the route involving an imidazole ring closure. The synthesis of L-eritadenine (IV) was achieved conveniently by direct condensation of adenine and L-erythronolactone acetonide (XX).

Summary Objective Superficial zone protein (SZP) has been shown to function in the boundary lubrication of articular cartilages of the extremities. However, the expression of SZP has not been clarified in mandibular cartilage which is a tissue that includes a thick fibrous layer on the surface. This study was conducted to clarify the distribution of SZP on the mandibular condyle and the regulatory effects of humoral factors on the expression in both explants and fibroblasts derived from mandibular condyle. Methods The distribution of SZP was determined in bovine mandibular condyle cartilage, and the effects of interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β) on SZP expression were examined in condyle explants and fibroblasts derived from the fibrous zone of condyle cartilage. Results SZP was highly distributed in the superficial zone of intact condyle cartilage. The SZP expression was up-regulated by TGF-β in both explants and cultured fibroblasts, whereas the expression was slightly down-regulated by IL-1β. A significant increase in accumulation of SZP protein was also observed in the culture medium of the fibroblasts treated with TGF-β. Conclusions These results suggest that SZP plays an important role in boundary lubrication of mandible condylar cartilage, is synthesized locally within the condyle itself, and exhibits differential regulation by cell mediators relevant to mandibular condyle repairing and pathologies.

We have studied the effects of urokinase (UK) on concentration changes of alpha 2 antiplasmin (alpha 2 AP) and on fibrino(geno)lysis. Medium dose (480,000 u) or large dose (960,000 u) of UK was given to each of seven normal volunteers by intravenous drip infusion within six hours, and then blood and urine analyses were carried out. Total alpha 2 AP, which includes free alpha 2 AP and alpha 2 AP-plasmin complex, decreased to about 50% of the original value with large dose of UK. alpha 2 AP-plasmin complex appeared in the plasma one hr after UK infusion and increased up to 50% of total alpha 2 AP at the end of UK infusion. B beta peptides, which are liberated from fibrin(ogen) at the very early stage of fibrino(geno)lysis, increased significantly with UK infusion, and was 65 times as much as the normal range at the end of UK infusion. Urinary B beta peptides increased as well as plasma B beta peptides. On the other hand, fibrin(ogen) degradation products (FDP) measured with enzyme immunoassay (EIA) increased only slightly, and moreover, urinary FDP was not detectable at any time. Plasma fibrinogen levels did not decrease and changed within the normal range in both groups. We then gave 960,000 u of UK to four patients with deep vein thrombosis and blood analyses were carried out as with normal volunteers. The most significant observation different from that of normal volunteers was shown in FDP levels. Serum FDP levels of four patients increased significantly in comparison with normal volunteers. Urinary FDP increased as significantly as plasma FDP. In conclusion, the infusion of 960,000 u of UK caused only very early stage of fibrinogenolysis without advanced fibrinogenolysis in normal volunteers, but in thrombotic patients, advanced fibrinolysis was observed.

The structures of the antibiotics FR-900098 (II) and FR-33289 (III), isolated from Streptomyces rubellomurius, have been established as 3-(N-acetyl-N-hydroxyamino)-propylphosphonic acid and 3-(N-acetyl-N-hydroxyamino)-2 (R)-hydroxypropylphosphonic acid, respectively, on the basis of spectroscopic and chemical evidence and, finally, by synthesis.

The synthesis of analogs of 3-(N-acetyl-N-hydroxyamino) propylphosphonic acid (FR-900098, Ia) and an analysis of their structure-activity relationship are described. Among them, compounds Ib (FR-31564) and XIIb (FR-32863) have recently been found to be produced naturally by Streptomyces lavendulae. The antibacterial activity of Ib against Pseudomonas species is especially significant.

The ankle systolic pressure was measured by the Doppler flow detector during the postoperative course after arterial reconstructive surgery in 61 limbs. The ankle systolic pressure was expressed as a pressure index (PI). There were 2 patterns in the recovery of PI after successful reconstructions. In one of these patterns, PI returned to the normal level within 24 hours. The other group represented a delayed recovery of PI. A comparative study between these 2 groups indicated that the delay in the recovery of PI may be chiefly related to a poor distal run-off. There was no relationship between the recovery pattern of PI and the late patency of reconstructed arteries. On the other hand, follow-up examination by means of the ankle pressure measurement was useful to detect new occurrences of stenotic lesions in the postoperative period.

A nocardicin derivative was prepared from penicillin G, confirming that nocardicins have the same configuration as penicillins at C-3 of the β-lactam ring.