Discovery, production and purification of the Na+, K+ activated ATPase inhibitor, L-681,110 from the fermentation broth of Streptomyces sp. MA-5038

The maximum yield for the production of L-681,110 by Streptomyces sp. MA-5038 (ATCC 31587) was observed after 5 days' incubation at 28 degrees C and pH about 8.3. L-681,110 was isolated from the fermentation broth by acetone extraction of the mycelia, absorption to Amberlite XAD-2 resin and two separations by thin-layer chromatography. The structure of L-681,110 was found to consist of a sixteen-membered lactone with a new type of substitution. The inhibition of ATPase, activity against Caenorhabditis elegans and stimulation of gamma-aminobutyric acid release indicate that L-681,110 possesses some characteristics of both oligomycin and avermectin. L-681,110 was also active against tapeworm and ticks in an in vivo assay.     

HMS Illustrious, OCEAN WAVE 97 and the medical branch.

As can be seen from the statistics, the challenges to all medical staff involved in OW97 were considerable. It is to the combined credit of all RN and RFA medical staff that a high standard of medical care was provided throughout the deployment. All operational casualties were treated correctly and without delay and most have made full recovery. Moreover, the varied general naval experience, foreign travel, new colleagues and friends gained from Global deployments such as this is something to be recommended. The authors wish to extend their thanks to all medical staff involved in OW97. Their support and hard work contributed significantly to make the medical aspects of the deployment such a success.     

Cephamycins, a New Family of β-Lactam Antibiotics I. Production by Actinomycetes, Including Streptomyces lactamdurans sp. n

A number of actinomycetes isolated from soil were found to produce one or more members of a new family of antibiotics, the cephamycins, which are structurally related to cephalosporin C. The cephamycins were produced in submerged fermentation in a wide variety of media by one or more of eight different species of Streptomyces, including a newly described species, S. lactamdurans. These antibiotics exhibit antibacterial activity against a broad spectrum of bacteria which includes many that are resistant to the cephalosporins and penicillins.     

Relative Morphological Effects Induced by Cefoxitin and Other Beta-Lactam Antibiotics In Vitro

Cefoxitin, a new semisynthetic cephamycin antibiotic, induced filament formation at subinhibitory concentrations with a beta-lactamaseless strain of Enterobacter cloacae (HSC 18410 M66). The extent of filament induction by cefoxitin was similar to that seen with cephalothin, cefazolin, and benzylpenicillin. Filament induction by cefoxitin was markedly less than that seen with cephalexin, carbenicillin, ticarcillin, cephradine, and cephapirin. Antibiotics which failed to induce filaments at any level tested included cephaloridine, cephacetrile, cephalosporin C, the cephamycins, 6-aminopenicillanic acid, 7-aminocephalosporanic acid, A16884, A16886, and FL-1060. Those antimicrobial agents tested which lacked an aromatic substituent in the 7-position (for cephems) or in the 6-position (for penams) did not induce filaments. These observations suggest a possible relationship between filament induction of the test organism and the molecular nature of constituents in the 7- or 6-position of beta-lactams.     

The α-helix folds on the millisecond time scale

It has long been believed that nucleation of the alpha-helix is a very fast reaction, occurring in around 10(-7) s. We show here that helix nucleation, in fact, takes place on the millisecond time scale. The rate of alpha-helix nucleation in two polyalanine-based peptides and in lysine and glutamic acid homopolymers was measured directly by stopped-flow deep UV CD with synchrotron radiation as the light source. Synchrotron radiation CD gives far superior signal to noise than a conventional instrument. The 16-aa AK peptide folds with first-order kinetics and a rate constant of 15 s-1 at 0 degrees C. The rate-determining step is presumably the initiation of a new helix, which occurs at least 10(5) times slower than expected. Helix folding occurs in at least two steps on the millisecond time scale for the longer peptides, with a transient overshoot of helix content significantly greater than at equilibrium, similar to that seen in the folding of several proteins. We suggest that the overshoot is caused by the formation of a single long helix followed by its breakage into the two or more helices present at equilibrium.     

Consequences of Aroclor 1254 ingestion on the menstrual cycle of rhesus (Macaca mulatta) monkeys.

A group of 80 female rhesus (Macaca mulatta) monkeys were randomly distributed to four similar test rooms (20 monkeys/room) and then randomly allocated to one of five test groups (four females/test group/room). The objective of the study was to ascertain the toxicological and reproductive effects of Aroclor 1254 ingestion at dose levels of 0, 5, 20, 40 or 80 microg Aroclor 1254/kg body weight per day (Arnold et al., 1993a,b, 1995, 1996, 1997). It was deemed necessary to establish the menstrual patterns for all the monkeys both before and after the start of dosing so as to provide an appropriate baseline from which potential treatment effects could be ascertained. The data presented herein were obtained during the first 3 years after the start of dosing, or the study's pre-mating phase. At the end of the first 2 years of dosing, the monkeys attained a qualitative pharmacokinetic steady state regarding the levels of polychlorinated biphenyls in their adipose tissue. Upon termination of the study, a number of monkeys were found to have endometriosis, adenomyosis or uterine leiomyomas (Arnold et al., 1996, 1997). These monkeys were designated as having gynecological abnormalities which were considered to be a factor in the analysis of the menstrual data. The menstrual data (i.e. menses frequency, cycle length and menses duration) were subjected to a statistical assessment to see whether year, quarter, gynecological abnormalities or dose of Aroclor 1254 had any effect on menses frequency, menstrual cycle length (i.e. the first day of menses until the day prior to the start of the next menses) and/or menses duration (i.e. the number of days of haemorrhagic discharge). The only consistent statistically significant effect found was that gynecological abnormalities increased menses duration (P<0.05) in all 12 quarters of the premating observation period. This effect was significant during both the pre- (P=0.0004) and post- (P< or =0.0001) pharmacokinetic steady-state intervals. While there was some indication of seasonality regarding menstrual cycle length and menses duration when these data were compared on a quarterly basis during the first 2 years of the study (P=0.043; P< or =0.0001, respectively), this effect was not evident during the third year (P=0.21; P=0.31, respectively). In particular, the effect of quarter on menses cycle length was most evident during the first year, with the shortest cycles occurring during the first or spring quarter and the longest in the third or fall quarter. However, menses duration was shortest in the first quarter during the first 2 years and tended to peak in the second quarter of all 3 years, while generally diminishing in the third and fourth quarters. There was also an increase in menses duration with increasing time on test for all groups. In addition, Aroclor 1254 treatment appeared to have some effect on menses duration when menses duration was plotted against dose group, but the effect was not statistically significant (P>0. 05). It was concluded that the ingestion of Aroclor 1254 at dose levels up to 80 microg/kg body weight/day by rhesus monkeys did not have any appreciable biological effect on menstrual frequency, menstrual cycle length or menses duration. However, gynecological abnormalities significantly increased menses duration during the three-year observation period.     

Postural responses to unexpected perturbations of balance during reaching

To study the interaction between feedforward and feedback modes of postural control, we investigated postural responses during unexpected perturbations of the support surface that occurred during forward reaching in a standing position. We examined postural responses in lower limb muscles of nine human subjects. Baseline measures were obtained when subjects executed reaching movements to a target placed in front of them (R condition) and during postural responses to forward and backward support-surface perturbations (no reaching, P condition) during quiet stance. Perturbations were also given at different delays after the onset of reaching movements (RP conditions) as well as with the arm extended in the direction of the target, but not reaching (P/AE condition). Results showed that during perturbations to reaching (RP), the initial automatic postural response, occurring around 100 ms after the onset of perturbations, was relatively unchanged in latency or amplitude compared to control conditions (P and P/AE). However, longer latency postural responses were modulated to aid in the reaching movements during forward perturbations but not during backward perturbations. Our results suggest that the nervous system prioritizes the maintenance of a stable postural base during reaching, and that later components of the postural responses can be modulated to ensure the performance of the voluntary task.