The crown-gall potato disk bioassay as a primary screen for compounds with antitumor activity.

A variety of samples consisting of purified compounds (of various origins) and ethanol extracts from plants were assayed for their activity on the growth and initiation of crown-gall tumors on potato disks. The results demonstrated a high correlation between the ability of these compounds to inhibit the initiation and growth of crown-gall tumors on potato disks and their corresponding activity on the mouse P388 leukemia protocol. Of the 21 compounds tested to date, there were two false-positives and one false-negative.

Preparation and antitumor activity of a rearranged ester of cephalotaxine.

For further evaluation of structure-activity relationships among the Cephalotaxus alkaloids, a "rearranged" ester (2b) of cephalotaxine was prepared, one which is an isomer of deoxyharringtonine (5a). The parent alkaloid, cephalotaxine (1a), was allowed to react with thionyl chloride to replace its hydroxyl group with chlorine. The resulting chloro compound 1b, on treatment with the silver salt of half ester 6, yielded 2b via an allylic rearrangement followed by further double bond migration. The new "rearranged" deoxyharringtonine isomer 2b proved to be inactive in the P-388 lymphocytic leukemia system and thus further delineated the structural requirements for antitumor activity in this series of alkaloids.

Cerebrospinal fluid eosinophilia and sterile shunt malfunction.

Cerebrospinal fluid (CSF) eosinophilia is a rare finding most often associated with central nervous system inflammatory processes, including parasitic, bacterial, and mycotic infections. It has also been seen as an allergic phenomenon. We present two cases of CSF eosinophilia occurring concurrently with sterile shunt malfunction. We speculate that CSF eosinophilia in our patients might have resulted from an allergic response to a foreign material such as suture, surgical glove powder, hair, cotton fibers, antibiotics, or silicone rubber. The incidence of sterile CSF eosinophilia after shunting is not known. Information concerning the role of eosinophilia in the development of shunt malfunctions is also lacking. An increased awareness of this possibility and further investigation are warranted.

Lenticonus in spina bifida. A case report.

A previously unreported association between spina bifida and anterior lenticonus is noted. The significance of this finding to the aetiology of some cases of spina bifida is discussed.

Postural response of intraocular pressure following traumatic hyphaema.

Twenty patients with previous unilateral traumatic hyphaema and 25 age-matched controls were studied. There was a progressive rise in intraocular pressure when the patient changed from the standing to the sitting position and then to the lying position in both groups. No control eye showed a rise greater than 2 mmHg when the subject changed from sitting to lying. However, 14 (70%) of the injured eyes and 12 (60%) of the fellow eyes showed an exaggerated response. We suggest that the presence of an abnormal postural response may indicate a predisposition to post-traumatic glaucoma. Our findings are compatible with a linked control of postural intraocular pressure response between the two eyes.

Postural response of intraocular pressure in chronic open-angle glaucoma following trabeculectomy.

Forty-six eyes with chronic open-angle glaucoma (COAG) and 24 eyes which had previously undergone trabeculectomy for COAG were studied and the postural response of the intraocular pressure compared with that of 70 normal eyes. In all three groups the greatest rise in intraocular pressure (IOP) occurred when the subject changed from the sitting to the lying position. In the control group this was never more than 2 mmHg in any subject. The rise was greater than 2 mmHg in 93% of the patients suffering from COAG who were treated medically and in 100% of the eyes of those on which trabeculectomy had been performed. The well recognised abnormal postural response of intraocular pressure in COAG appears both to be retained and to be unaffected in those eyes which have undergone trabeculectomy.

cis-5,cis-9,cis-12-octadecatrienoic and some unusual oxygenated acids inXeranthemum annuum seed oil.

Seed oil ofXeranthemum annuum (family Compositae) contains a number of unusual fatty acids in addition to palmitic, stearic, oleic, linoleic and linolenic. These acids includecis-5,cis-9,cis-12-octadecatrienoic, 5%;cis-9-L: ,10-L: -epoxyoctadecanoic, 3%;cis-9-L: ,10-L: -epoxy-cis-12-octadecenoic (coronaric), 8%; andcis-12-D: ,13-D: -epoxy-cis-9-octadecenoic (vernolic), 2%; as well as a mixture of two hydroxy acids, 11%. The absolute configurations of the two 9,10-epoxy acids are established for the first time.

The effect of alkaloids and seed extracts of endophyte-infected tall fescue on prolactin secretion in an in vitro rat pituitary perfusion system.

The objective of this research was to measure the effects of endophyte-infected tall fescue seed extract and various alkaloids associated with the endophyte on in vitro prolactin secretion by rat hemipituitaries. Rat anterior pituitaries (AP) were dissected into halves and placed in temperature-controlled culture chambers (37 degrees C). The tissue was perfused with culture media at a flow rate of 12 mL/h. After perfusion for at least 90 min with control media, AP halves were exposed to their respective treatments for 15 min before they were returned to the control media. The treatments for Exp. 1 were .01 micrograms of alpha-ergocryptine/mL of culture medium, .01 microgram of ergonovine/mL of culture medium, .01 gram-equivalents of endophyte-infected tall fescue seed/mL of culture medium, and .01 gram-equivalents of endophyte free tall fescue seed/mL of culture medium. Treatments for Exp. 2 consisted of 10(-4), 10(-6), and 10(-8) M concentrations of perloline, N-formyl loline, N-acetyl loline, N-methyl loline, and alpha-ergocryptine. alpha-Ergocryptine suppressed (P less than .10) prolactin secretion in both experiments. Ergonovine and perloline both stimulated (P less than .10) prolactin secretion. The loline alkaloids (N-formyl loline, N-acetyl loline, N-methyl loline) had no effect on prolactin secretion. The endophyte-infected seed extract treatment suppressed (P less than .10) prolactin secretion. The endophyte-free seed extract treatment had no effect on prolactin secretion. In Exp. 2, prolactin secretion from AP responded to alpha-ergocryptine treatment in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloid toxins in endophyte-infected grasses.

Grasses infected with clavicipitaceous fungi have been associated with a variety of diseases including classical ergotism in humans and animals, fescue foot and summer syndrome in cattle, and rye-grass staggers in sheep. During the last decade it has been recognized that many of these fungal infections are endophytic; a fungal endophyte is a fungus that grows entirely within the host plant. Inspection of field collections and herbarium specimens has revealed that such infections are widespread in grasses. The chemistry associated with these grass-fungal interactions has proved to be interesting and complex, as each grass-fungal pair results in a unique "fingerprint" of various alkaloids, of which some are highly toxic to herbivores. In many cases the presence of an endophyte appears to benefit the plant by increasing drought resistance, or by increasing resistance to attack by insects, thus improving the overall survivability of the grass. This review will focus on alkaloids that have been reported in endophyte-infected grasses.

Interrelation of the common congenital malformations: some aetiological implications.

Analysis of congenital defects in a population of 90 921 singleton births revealed a strong interrelation between malformations: for example, 84% of lung defects, 70% of kidney defects, 34% of eye defects, 19% of cleft palate, and 15% of spina bifida coexisted with other defects which could not be designated as subsequently derived structural changes. The strength and intimacy of these interrelations casts doubt on the notion that multiple external factors are involved in the causation of human malformations.

An investigation of the antitumor activity of Sesbania drummondii.

Extracts of Sesbania drummondii (Rydb.) Cory seed are active in vivo in the P-388 lymphocytic leukemia system and cytotoxic in the KB assay. Systematic fractionation of S. drummondii has yielded sesbanine (1), a novel spirocyclic alkaloid based on the 2,7-naphthyridine nucleus, and drummondol (2), a new abscisic acid (5) metabolite. Sesbanine and drummondol are present in highly cytotoxic fractions; however, these purified compounds are essentially devoid of antitumor activity

Prostaglandin generation by separated human blood mononuclear cell fractions.

Prostaglandins (PGs) have been widely implicated as modulators of immuno-inflammatory reactions. The cellular source of such immunoregulatory PGs has generally been thought to be the macrophage/monocyte, however several workers have suggested that adherent T-lymphocytes may be involved. We have attempted to resolve this question and have assayed PGE2 and thromboxane B2 release by purified sub-populations of human blood lymphocytes. Separated lymphocyte populations produce little PGEs when compared to monocytes and we concluded that the levels of PGs generated could be explained by monocyte contamination. In conclusion, we feel that the monocyte/macrophage acts as the source of immunoregulatory prostaglandins.