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Excessive longitudinal segmentation of the radial portion of the limb bud results in the clinical presentation of duplicated and triphalangeal thumbs. These are common congenital problems with various possible associated anomalies and variable inheritance patterns. Reconstruction of a thumb with stable joints, muscle balance, and good alignment requires attention to each tissue component at the time of the initial surgery.

Three human pancreatic cancer cell lines, designated as KP-1N, KP-2 and KP-3 have been established in both tissue cultures and in nude mice. The KP-1N and KP-3 tumors were obtained from liver metastases of pancreatic tumors and the KP-2 tumors was of primary pancreatic origin. The patients' tumors from which KP-1N and KP-2 were derived showed characteristics of adenocarcinoma, and the KP-3 tumor had adenosquamous carcinoma characteristics. Inoculations of samples from surgical specimens into athymic nude mice resulted in tumor formation, with the tumors histologically closely resembling the original neoplasms. Subcutaneous injections of the established cell lines also induced tumor formation and the tumors histologically resembled the original lesion in the cases of KP-2 and KP-3 tumors, but the KP-1N tumors in the mice were histologically different from the surgical specimen. The KP-1N, KP-2 and KP-3 cell lines have been cultured continuously in a medium supplemented with 10% fetal calf serum for more than 20, 21 and 17 months, respectively. The KP-2 and KP-3 cell lines produced and released carbohydrate antigen 19-9 into the spent medium but the KP-1N cell line did not. KP-1N and KP-3, produced liver metastases after intrasplenic injection into nude mice, whereas KP-2 produced few liver colonies. Cell lines highly metastatic to the liver, KP-1NLs and KP-3Ls, were isolated from the liver colonies of KP-1N and KP-3, respectively.

Streptoverticillium fervens produced a new antibiotic, FR-900848, which has a high specific activity against filamentous fungi. Purified by solvent extraction and column chromatography, the compound appears as colorless crystals. Its structure is C32H43N3O6, which consists of 5'-amino-5'-deoxy-5,6-dihydrouridine with an unsaturated fatty acid having unprecedented four serial and one isolated cyclopropane rings.

FR112123 is a new oligopeptide antibiotic produced by Streptomyces viridochromogenes No. 7587. The structure of FR112123 is elucidated as N-(N6-(N2-glycyl-L-glutaminyl)-D-lysyl)-D-alanine (1) by spectroscopic and chemical evidence. It resembles a partial structure of peptidoglycan in bacteria. The compound has a superior activity against an Escherichia coli mutant sensitive to inhibitors of cell wall synthesis, although it has a weak activity against the parent strain. These suggest that FR112123 might act on the biosynthesis of bacterial cell wall.

FR109615, a new antibiotic active against Candida, was isolated from Streptomyces setonii No. 7562. Based on the spectroscopic data, the structure of FR109615 was elucidated as cis-2-aminocyclopentane-1-carboxylic acid (1). The compound showed the excellent in vivo efficacy in a generalized infection test of mice.

WS1358A1 (FR104007) and B1 (FR104008), new potent inhibitors of renal dehydropeptidase, were isolated from the culture broth of strain No. 1358 which was identified as Streptomyces parvulus subsp. In vitro inhibitory activities (IC50 value) of WS1358A1 and B1 against porcine renal DHP were 3 and 600 nM, respectively.

MCNU is a new derivative of nitrosourea and experimental studies have shown equal or superior activity to known nitrosourea compounds. Twenty one cases were entered into our clinical studies with a phase II study. Nineteen cases have had a several courses of prior chemotherapy. Four out of 21 cases achieved a partial response (each one of lymphoepithelioma, parotid gland cancer, recurrent uterine cancer and recurrent breast cancer). The major toxicity encountered during treatment was myelosuppression. Full recovery of myelosuppression was delayed and was seen six to eight weeks after each injections. These initial results justify further clinical investigations with MCNU.

Biphenomycin A, C23H28N4O8, and biphenomycin B, C23H28N4O7, were isolated from the cultured broth of Streptomyces griseorubiginosus No. 43708. The antibiotics are active in vitro and in vivo against bacteria, and are especially potent against Gram-positive bacteria. The acute toxicity of biphenomycin A is very low in mice.

Rat liver cytosol was previously shown to contain at least three NADPH-dependent enzymes which catalyze the hydrogenation of chloral hydrate. Two of them had previously been shown to catalyze the hydrogenation of long-chain aliphatic and aromatic aldehydes or aromatic ketones in addition to halogenated acetaldehydes. The present paper demonstrates that one of these enzymes also catalyzes the reversible hydrogenation of 3-oxosteroids to 3 alpha-hydroxysteroids. We confirmed that the enzyme catalyzes the reversible hydrogenation of C23, C24 and C26 3-oxo bile acids with a 1:1 stoichiometry. The substitution at C-12 with a hydroxyl group markedly decreased the reaction rate, and the rate of dehydrogenation of C20, C23, C26, C24, and C25 bile acids decreased in the descending order. In general, the conjugation with glycine or taurine increased the reaction rate, while the replacement of the terminal carboxyl group of the C24 compound with an isobutyl group markedly decreased it. 3 alpha-Hydroxy bile acids with A/B trans configuration were also preferable substrates for the enzyme, although the reaction rate was relatively low compared with that of those with A/B cis configuration. The enzyme may be involved in the biosynthesis of lithocholic acid from cholesterol through 3 alpha-hydroxy-5-cholen-24-oic acid, which was proposed by Mitropoulos and Myant (Mitropoulos & Myant (1967), Biochem. J. 103, 472--479).

A new antitumor antibiotic, FR900840, was isolated from a culture broth of Streptomyces strain No. 8727 as a pale yellowish prism and the molecular formula was determined to be C7H11N3O5. The antibiotic exhibited prominent antitumor effects on human tumor cell lines both in vitro and in vivo.

Recently, there has been an increasing interest in the diagnostic and prognostic usefulness of tumor-associated antigen of embryonic and fetal origin. Many approaches have been attempted to make an early diagnosis of the pancreatic cancer, where a specific screening blood test for the pancreatic cancer is required. By using antiserum to fetal pancreas, Banwo et al, discovered an oncofetal antigen that was present in human fetal pancreas, pancreatic tumor tissue, and sera from patients with the pancreatic cancer. Pancreatic oncofetal antigen (POA) was considered to be an oncofetal antigen for human pancreas, and its measurement seemed to be useful in the diagnosis of pancreatic cancer. But elevated levels of POA were also observed in the serum of some patients with cancer of the stomach, lung, colon, or liver as well as in the serum of some pregnant women and others with certain benign conditions. In summary, combined assay with various tumor markers was considered to be useful for the diagnosis of pancreatic cancer.

Lavendomycin, a new basic peptide antibiotic containing novel amino acids, has been isolated from the culture broth of a streptomyces designated as Streptomyces lavendulae subsp. brasilicus. The antibiotic obtained as colorless crystals (C29H50N10O8, MW 666) is active against Gram-positive bacteria in vitro and in vivo, however, inactive against Gram-negative bacteria and fungi. An acute toxicity of the antibiotic in mice was LD50 greater than 2 g/kg by subcutaneous injection.

The structures of biphenomycins A and B, novel peptide antibiotics produced by a strain of Streptomyces, have been established as 1 and 2, respectively, on the basis of spectroscopic and chemical evidence. They are unique in that they are cyclic peptides containing a biphenyl moiety included in a 15-membered ring and show potent antibacterial activities especially against Gram-positive bacteria.