Showing papers by "Eli Lilly and Company published in 1971"
TL;DR: This study investigates factors that normally cause variation in zone diameters in conventional disc plate diffusion assay procedures and forms the basis for a test protocol which is presented in a following paper.
Abstract: Several factors are investigated that normally cause variation in zone diameters in conventional disc plate diffusion assay procedures. Of these factors the most serious is the unequal exposure of the individual plates at top or bottom of stacks to temperatures above and below room temperature. This unequal temperature exposure is avoided by novel handling and incubation procedures. A major variable, but one which can be controlled, is the varying time interval between pouring seeded agar and the time of applying the pads with antibiotic to the plates. This influence of time of setting and the effects of several other sequential operations are combined into a composite variable. This variable is then accounted for and normalized by interposing “external” reference plates set with a reference solution in the sequence of approximately 100 plates. No “internal” reference zones are employed. Such factors as volume of agar poured, wedge shape of agar in a dish, volumetric errors in dilutions, and timing considerations are studied and discussed. The results of this study form the basis for a test protocol which is presented in a following paper.
214 citations
TL;DR: Bacillus subtilis was most commonly employed, but other organisms may be employed in the present procedure, which is economical, uses simple facilities, and provides good accuracy of test results.
Abstract: A detailed disc plate procedure is introduced for assay of antibiotics. The procedure is based on a previous study by the authors and deviates from conventional procedures in several respects: selected plastic petri dishes are employed; critical temperature control is simply provided at all stages of the test with refrigeration of the plates never used; all dilution is done with displacement microburettes; six pads (6.3 mm diameter) per dish are employed, all filled with the same unknown or reference solution; the sequence of all plates handled on 1 day is made a part of the protocol which allows accounting for the influence of the order of pouring and setting the plates; external reference plates are set at specified locations in the sequence; and, by averaging the diameters of all zones on a plate, most of the consequence of wedge shape of agar in plates, which is common and almost unavoidable, is removed. The present method is economical, uses simple facilities, and provides good accuracy of test results. Bacillus subtilis was most commonly employed, but other organisms may be employed in the present procedure.
140 citations
TL;DR: In submerged cultures, Cephalosporium acremonium exists in four morphological forms: hyphae, arthrospores, conidia, and germlings, which exhibit enhanced synthesis of beta-lactam antibiotics and appear to be a determining factor in high-yielding mutants.
Abstract: In submerged cultures, Cephalosporium acremonium exists in four morphological forms: hyphae, arthrospores, conidia, and germlings. The phase of hyphal differentiation into arthrospores coincides with the maximum rate of beta-lactam antibiotic synthesis. Furthermore, arthrospores, separated by density-gradient centrifugation, possess 40% greater antibiotic-producing activity than any other morphological cell type. In a series of mutants, each with an increased potential to produce beta-lactam antibiotics, differentiation into arthrospores was proportional to the increased titer of these antibiotics. Thus, arthrospores exhibit enhanced synthesis of beta-lactam antibiotics and appear to be a determining factor in high-yielding mutants. Since a non-antibiotic-producing mutant readily differentiated into arthrospores, antibiotic synthesis and cellular differentiation are not obligately related.
81 citations
76 citations
TL;DR: The human differs from the rat and dog in that propoxyphene metabolites are eliminated primarily in urine rather than bile, and the half-life of norpropoxymhene is also substantially longer than that of prop oxyphene.
75 citations
TL;DR: Differences in plasma concentrations following the 2 salts were small in comparison with those among subjects and among doses and it was concluded that these differences had little, if any, therapeutic importance.
73 citations
65 citations
TL;DR: The significant difference in latency for onset of hormone secretion suggests that LH and FSH may be controlled by 2 separate neuronal networks which could not be resolved by the stimulus employed in this study.
Abstract: Plasma levels of LH and FSH were determined by radioimmunoassay following electrochemical stimulation of various brain areas. Stimulation of many sites in an area of the brain beginning in the medial septum and extending through the preoptic area (POA) and anterior hypothalamic area (AHA) and terminating in the median eminence arcuate complex (MEAC) resulted in highly significant increases in plasma LH levels. Approximately 80 % of the sites in-the POA, AHA and MEAC which were found to be stimulatory to LH were also stimulatory to FSH secretion. Plasma LH levels were highest 0.5 hr after stimulation of the POA, AHA and MEAC, while FSH levels did not increase until 3.0 hr after stimulation. The significant difference in latency for onset of hormone secretion suggests that LH and FSH may be controlled by 2 separate neuronal networks which could not be resolved by the stimulus employed in this study. It was also noted that medial septal stimulation caused a much more prolonged increment in LH secretion than ...
37 citations
TL;DR: In these studies several pregnancies were followed in which methadone maintenance was initiated before or during pregnancy with no apparent effect, and although women experienced abnormal menses during heroin addiction, regular menstruation and ovulation resumed with daily methadones treatment.
Abstract: METHADONE maintenance was reported as a treatment for heroin addiction in 19651, and more than 10,000 patients are now maintained on the drug at more than 100 centres throughout the United States (unpublished Lilly Survey, 1970). Wallach et al.2 observed that although women experienced abnormal menses during heroin addiction, regular menstruation and ovulation resumed with daily methadone treatment. In these studies several pregnancies were followed in which methadone maintenance was initiated before or during pregnancy with no apparent effect.
34 citations
TL;DR: A portion of the fermentation research program was directed towards isolating analogue-resistant mutants which were insensitive to feedback regulation and induced from the wild-type pyrrolnitrin strain (Pseudomonas fluorescens A1033).
Abstract: Pyrrolnitrins are a group of closely-related phenylpyrrole antibiotics synthesized from D-tryptophan by several species of Pseudomonas (Elander et al., 1968). The bacterium first shown to synthesize pyrrolnitrins in our laboratories was reported to be closely related to Pseudomonas aureofaciens (Lively et al., 1967). The strain has now been more properly classified as Pseudomonas f luorescens (Biotype E) following the system of classification proposed by Stanier et al. (1966). Biosynthetic studies have shown that D-tryptophan is a direct precursor of the antibiotic and that additions of Dtryptophan stimulate pyrrolnitrin synthesis (Lively et al., 1967; Hamill et al., 1967). However, the amounts of Dtryptophan required for maximal synthesis and the high cost of the amino acid made exploitation of this interesting discovery in large-scale production fermentors virtually impossible. With these facts in mind, a portion of our fermentation research program was directed towards isolating analogue-resistant mutants which were insensitive to feedback regulation. A number of strains resistant to 5-fluorotryptophan (5-FT) and 6-fluorotryptophan (6-FT) were induced from the wild-type pyrrolnitrin strain (Pseudomonas fluorescens A1033.8). The mutants were examined for their capacity to synthesize pyrrolnitrin in both tryptophan-supplemented and non-tryptophan-supplemented media. The results of these studies a r e described in this report.
33 citations
TL;DR: Simplified culture techniques and an automated system for monitoring both the chronotropic and inotropic effects of chemical and physical agents are developed.
Abstract: IN recent studies with cultured beating heart cells1–5 data have usually been acquired by intermittent microscopic observations of the contractions of the cells. The more laborious method involving measurement of intracellular electrical depolarization is too expensive for routine use6. We therefore set out to develop simplified culture techniques and an automated system for monitoring both the chronotropic and inotropic effects of chemical and physical agents.
TL;DR: While depression was a more persistent state among patients than controls, it was not found to be age-related among either patients or controls and the implication of these findings in planning strategies of therapeutic intervention to circumvent the cumulative effects of anxiety and depression is discussed.
Abstract: A Markov process analysis was applied in a study of anxiety and depression patterns among 31 male patients with coronary heart disease and 46 healthy male controls. Anxiety and depression were measured at six- to eight-week intervals over a period of 15 months by the subjects' completion of shortened versions of the Bendig Anxiety and Welsh Depression subscales of the MMPI. The sequence of anxiety and depression states for each subject at each examination was used as input to the Markov analysis system. Patients had significantly higher anxiety scores over time than the controls. Patients under age 50 showed a fivefold greater incidence of anxiety and a higher degree of retention of high anxiety over time than controls in the same age group. The anxiety level of controls was low irrespective of age. While depression was a more persistent state among patients than controls, it was not found to be age-related among either patients or controls. The implication of these findings in planning strategies of therapeutic intervention to circumvent the cumulative effects of anxiety and depression is discussed.
TL;DR: The objective of this investigation was to compare the number ofHeparin units neutralized by protamine sulfate as a function of heparin source, potency, and manufacturing process.
TL;DR: It was concluded that differences in plasma concentrations following these salts were small in comparison with those among subjects and among doses, and had little, if any, therapeutic importance.
TL;DR: Comparative acute oral toxicity tests on the 2-naphthalene sulfonate (napsylate) salt of propoxyphene indicated that the differences in the acute oraloxicity of prop oxyphene HCl and propoxylate were due to the more gradual absorption of the latter salt.
TL;DR: It was concluded that the POA may be an important mediator of the often encountered reciprocal relationship between gonadotropin and prolactin release.
Abstract: Plasma levels of LH and prolactin were measured by radioimmunoassay after stimulation of the preoptic area (POA) and basal medial hypothalamus (BMH) Stimulation of the BMH resulted in increased plasma levels of LH and prolactin In contrast, stimulation of the POA elicited increased plasma LH but produced a decrement in prolactin levels It was concluded that the POA may be an important mediator of the often encountered reciprocal relationship between gonadotropin and prolactin release
TL;DR: Fenoprofen, administered orally as the sodium or calcium salt, was readily absorbed from the GI tract; however, absorption after the calcium salt was delayed slightly compared to the sodium salt.
TL;DR: Guinea pigs sensitized with zonal-centrifuged purified duck embryo vaccine (with AlPO(4) adjuvant) did not exhibit anaphylactic shock reactions when challenged with homologous vaccine, and these vaccines also induced good sero-conversion in adult rabbits after a single 1-ml dose of vaccine.
Abstract: Rabies virus produced in duck embryo cell culture was concentrated from volumes of 14 to 30 liters to 400 to 800 ml by zonal centrifugation. Virus titers of peak fractions were from 100- to 1,000-fold greater than those of the starting material. Vaccines were prepared by combining fractions with peak virus titers and diluting back to 10 times concentration. The resulting β-propiolactone-inactivated vaccines, when prepared as lyophilized vaccines with AlPO4 adjuvant diluents, were low in protein nitrogen (0.01 mg/ml), and three of four lots passed the National Institutes of Health potency test when tested as equivalent to a standard 10% suspension of duck embryo or mouse brain tissue vaccine. These vaccines also induced good sero-conversion in adult rabbits after a single 1-ml dose of vaccine. Guinea pigs sensitized with zonal-centrifuged purified duck embryo vaccine (with AlPO4 adjuvant) did not exhibit anaphylactic shock reactions when challenged with homologous vaccine. Also, no anaphylactic shock reactions were observed when guinea pigs were sensitized with either a 10% experimental duck embryo vaccine or cell culture vaccine and then challenged with the zonal-purified vaccine. However, guinea pigs sensitized with cell culture or zonal-purified vaccine and then challenged with the 10% experimental vaccine did show slight transitory congestion. The 10% experimental whole duck embryo vaccine was responsible for all observed anaphylactic shock reactions whether homologous or heterologous.
Patent•
14 Jun 1971TL;DR: New 3-(substituted) vinyl cephalosporin compounds, e.g., 3-(2'-ethoxycarbonylvinyl)-7-phenoxyacetamido-3-cephem-4-carboxylic acid, which are useful as antibiotics, were proposed in this article.
Abstract: New 3-(substituted) vinyl cephalosporin compounds, e.g., 3-(2'-ethoxycarbonylvinyl)-7-phenoxyacetamido-3-cephem-4-carboxylic acid, which are useful as antibiotics, and 3-(substituted) vinyl cephalosporin compounds which are useful as intermediates in preparing antibiotic substances.
TL;DR: For example, at the level of 0.5 mg/ml of free hexosamine, d -glucosamine gave an apparent protein level of 1.055 mg/m and d -galactosamine 0.070 mg/mm as mentioned in this paper.
TL;DR: Claviceps purpurea has been shown to produce extracellular l-tryptophan from indole in stirred fermentors, and the substrate specificity of this conversion was investigated by using substituted indoles, anthranilic acid, and 4-chloro-anthranilic acids.
Abstract: Claviceps purpurea has been shown to produce extracellular l-tryptophan from indole in stirred fermentors. The substrate specificity of this conversion was investigated by using substituted indoles, anthranilic acid, and 4-chloro-anthranilic acid. Addition of 2-, 4-, 5-, 6-, and 7-methyl indole or 6-chloroindole to C. purpurea C1M produced the corresponding substituted l-tryptophan. In contrast, addition of l-methyl, 6-trifluoromethyl, 6-nitro-, or 4-benzyloxy-substituted indoles, or anthranilic and 4-chloroanthranilic acids did not produce detectable amounts of the corresponding tryptophan.
TL;DR: An assay procedure for quantitating aminoglycosidic or polymyxin antibiotics after enzymatic degradation of a coexisting beta-lactam antibiotic is described.
Abstract: Monitoring of serum concentrations of aminoglycosidic or polymyxin antibiotics when administered concurrently with cephalosporins or penicillins requires a special assay technique. Selective enzymatic degradation of the β-lactam antibiotic from the serum specimen allows subsequent assay of the antibiotic being monitored. This report gives details of a simple procedure for laboratory production of a crude enzyme capable of degrading cephalosporins or penicillins. An assay procedure for quantitating aminoglycosidic or polymyxin antibiotics after enzymatic degradation of a coexisting β-lactam antibiotic is described. Images
TL;DR: Tritium from C-2 of the side chain of L-, although not of D-tryptophan, is retained in the biosynthesis, suggesting that formation of the double bond at this carbon atom occurs simultaneously with or subsequent to the removal of the carboxyl group.
TL;DR: Progesterone may have raised the threshold for excitation of neurons in the CNS which are capable of eliciting prolactin release in response to stress and EB may have a direct action on the pituitary to amplify the effects of small changes in hypo- thalamic inhibiting and/or stimulating factor secretion.
Abstract: A study was performed to deter- mine the influence of ovarian steroids on the ability of an electrochemical stimulus or sham stimulus placed in the median eminence arcuate area to elicit prolactin release in ovariectomized rats. Both sham stimulation and electrochemical stimulation caused prolactin release in rats treated with 2 \ig of estradiol benzoate (EB). Rats receiv- ing simultaneous administration of 4 mg of pro- gesterone and 2 u,g of EB developed high serum prolactin levels in response to electrochemical stimulation, but had unchanged levels after sham stimulation. The reasons for this may be that the urethane anesthesia combined with stereotaxic immobiliza- tion and surgery created a stressful condition that influenced prolactin secretion in these animals. Estrogen appeared to act by lowering the threshold for excitation of neurons that respond to stressful stimuli, and also lower thresholds of neurons that inhibit prolactin inhibiting factor (PIF) secreting neurons or stimulate prolactin stimulating factor (PSF) neurons. Progesterone may have raised the threshold for excitation of neurons in the CNS which are capable of eliciting prolactin release in response to stress. The possibility also exists that EB may have a direct action on the pituitary to amplify the effects of small changes in hypo- thalamic inhibiting and/or stimulating factor secretion. (Endocrinology 89: 1317, 1971) T>ROLACTIN concentration in the anterior •*• pituitary (AP) of the rat markedly increases
TL;DR: Two salts of d -propoxyphene, the hydrochloride and the 2-naphthalene sulfonate (napsylate), were compared in short-term toxicity studies in rats and dogs and the effects produced by daily administration of equimolar doses of these salts were indistinguishable.