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PubMed1979

Nocturnal and diurnal sleep in Macaca sylvana.

In Macaca sylvana restrained in chairs, continuous 24 h recordings were obtained of scalp EEG, neck EMG, bilateral EOG, motility of the head and lever manipulation. A total of 32 days were studied in 8 monkeys. Recordings were divided into epochs of 30 sec and analyzed in a PDP-12 computer. Four stages of sleep and 5 stages of wakefulness were identified by combination of the above data. Results were as follows: (1) During the night, there was 21% wakefulness and during the day 20% sleep, including a considerable amount of REM. (2) Recordings of spontaneous motility of head and hands proved an excellent indicator of sleep-wakefulness cycles. (3) Spectral analysis revealed the cyclic characteristics of non-REM sleep, with peaks at 360, 149, 72, and 55 min. (4) Stages of wakefulness had ultradian cycles, and stage W-2 was the most important in number and duration of occurrences. (5) Night wakefulness had characteristics different from day wakefulness. (6) Study of sequences showed that stage II was the least differentiated being transitional among the other stages, while stage III-IV was never preceded by wakefulness or REM, and almost always it followed stage II (99.0% of the time). (7) The high statistical significance of results obtained under restraint in different monkeys suggests that this situation has great potential value in the investigation of physiological mechanisms of ultradian rhythms.

Animals↗
PubMed1987

Transcriptionally defective nucleocapsids of vesicular stomatitis virus from cells treated with indomethacin.

Indomethacin blocks the biosynthesis of vesicular stomatitis virus (VSV) at the level of primary transcription, RNA replication, and protein synthesis (P. K. Mukherjee and R. W. Simpson (1985), Virology 140, 188-191). Nucleocapsids of infecting virus particles recovered from indomethacin-treated cells were analyzed for in vitro transcriptase activity. Incorporation of [3H]UTP in mixtures containing nucleocapsids from HEp-2 cells pretreated with 10(-3) M indomethacin was inhibited approximately 80% compared to control reactions containing nucleocapsids from untreated infected cells. The level of inhibition of in vitro transcriptase activity of viral nucleocapsids from drug-treated cultures varied according to the cell line used for infection. After indomethacin removal, cells regained their ability to produce enzymatically competent viral-transcribing complexes unless they were subsequently exposed to metabolic inhibitors such as actinomycin D or alpha-amanitin. Enzymatically defective nucleocapsids from indomethacin-treated cells showed enhanced in vitro transcriptase activity in the presence of modulators of prostaglandins and cyclic nucleotides. Electrophoretic analysis of product from in vitro transcriptase reactions revealed that these defective nucleocapsids are unable to synthesize VSV messenger RNA or normal size leader RNA species but only smaller transcripts of undetermined identity.

Animals↗
PubMed2005

Ontogeny and effects of thyroid hormone on beta1-adrenergic receptor mRNA expression in ovine fetal kidney cortex.

OBJECTIVE: Previous studies indicate that thyroidectomy (TX) decreases renin gene expression in ovine fetal renal cortex in late gestation. Fetal ovine renin-containing renocortical cells become increasingly responsive to beta-adrenergic stimulation as gestation proceeds. Increases in plasma thyroid hormone concentrations parallel this change, suggesting that there is a positive developmental relationship between the two. To examine this hypothesis, we determined the ontogeny of beta1-adrenergic receptor (beta1R) mRNA expression, and the effect of thyroid hormone on in vivo and in vitro expression in fetal sheep. METHODS: Renocortical tissue was obtained from naive, TX, and sham-operated fetuses to determine beta1R mRNA levels. Renin-containing renocortical cells from TX or sham fetuses were treated with isoproterenol (Iso) or forskolin (FSK) for analysis of cellular cyclic adenosine monophosphate (cAMP) levels. Renocortical cells from naive fetuses were treated with triiodothyronine (T3) to assess cellular beta1R mRNA levels. Fetal plasma thyroxine (T4) level was determined. RESULTS: Renocortical beta1R mRNA expression increased significantly between 100 and 140 days' gestational age (dGA), while TX attenuated this increase (P <.01). Renocortical cellular cAMP levels were higher in sham compared to TX fetuses following incubation with Iso or FSK (P <.05). Cells incubated with T3 exhibited significantly increased beta1R mRNA expression (P <.05). CONCLUSION: The data suggest that thyroid hormone may be involved in modulating ovine fetal renocortical beta1R gene expression during development. We speculate that the increased beta1R mRNA expression in renal cortical cells as development progresses may mediate the increases in renin gene response to beta-adrenergic stimulation in late gestation.

Adrenergic beta-Agonists↗
PubMed2006

Reproduction and embryonic diapause in a marsupial: insights from captive female Honey possums, Tarsipes rostratus (Tarsipedidae).

The reproductive physiology of the polyoestrous Honey possum (Tarsipes rostratus) is virtually unknown except that it shares with the kangaroos and wallabies the phenomenon of embryonic diapause. Its tiny size necessitates an alternate approach to study their reproductive cycle. We have accordingly utilised faecal steroid analysis. Baseline faecal cortisol levels in the Honey possum, at 4.1+/-0.3 mug g-1, are approximately 100-fold those of other mammals and are associated with adrenal glands that, on a mass-specific basis, are almost 10 times larger than the adrenals of other mammalian, including marsupial, species. Histological examination of the adrenal glands revealed no abnormalities, however, but their hypertrophy and the peaks recorded in faecal levels following disturbance suggest that the Honey possum is vulnerable to chronic stressors in the captive situation. Mean faecal progestagens (124.4+/-107.3 ng g-1) and oestradiol-17beta (4.1+/-1.1 ng g-1) in 4 non-pregnant females maintained long term were not different from those of 5 pregnant females (101.4+/-61.0 ng g-1 and 4.3+/-1.5 ng g-1, respectively) and, on analysis, revealed a cyclicity of 24+/-1.2 days. We would predict from this evidence that the gestation period, in the absence of lactation, is approximately 23 days. Four of the pregnant females, monitored from July to November under conditions of 10:14 L:D photoperiod, showed a fall in levels of progestagens from 175.9+/-10.8 ng g-1 in July and August to 30.9+/-9.4 ng g-1 in October, while mean faecal levels of oestradiol-17beta increased from 3.8+/-0.4 ng g-1 in July to 5.7+/-0.3 ng g-1 in October. September and October are months of peak reproductive activity in the wild and we suggest that these hormonal modulations may represent an entrained reproductive rhythm. Blastocysts appear to develop at varying rates, both within the one uterus, and between the two uteri of a single female. In addition, the time taken to reach the blastocyst stage may be longer than in any other marsupial studied to date. An association of the age of the pouch young with the stage reached by the developing blastocyst does not support the conclusion that blastocysts, once formed, grow slowly during lactation or diapause. Contrary to previous reports, we have documented what appears to be a lactational inhibition on blastocysts in diapause and have estimated the length of the 'delayed' reproductive cycle in two females as less than 2 weeks. Reactivation of blastocysts in Tarsipes has been shown to be stimulated by shortening day lengths after the summer solstice, a response similar to the annual breeding period of macropodid marsupials. Results from studying Honey possums in captive conditions suggest that the control of diapause in Tarsipes appears to be three-fold; lactational, photoperiodic and an entrained rhythm.

Animals↗
PubMedDate not supplied

Panic disorder patients have reduced cyclic AMP in platelets.

Little is known about the intracellular mechanisms involved in the pathophysiology of panic disorder (PD). Abnormalities in the cyclic AMP system have been described in several psychiatric disorders but there are no studies in panic patients. We evaluated not only the levels of platelet cyclic AMP, but also cyclic GMP and nitric oxide synthase (NOS) activity in patients with PD at baseline and after treatment with clomipramine and in healthy volunteers. Platelet cyclic AMP was determined by enzymeimmunoassay, cyclic GMP by radioimmunoassay and NOS activity by the conversion of (3)H-arginine to (3)H-citruline in 17 PD patients before treatment with clomipramine, after remission of panic attacks and in 22 healthy volunteers. Average baseline cyclic AMP of PD patients was lower than after remission of panic attacks (P<0.005) and lower than in healthy volunteers (P<0.005). Average cyclic AMP after remission of panic attacks was not significantly different than in healthy volunteers. There were no significant differences in cyclic GMP and NOS analysis. Our results suggest that PD patients without treatment have lower platelets cyclic AMP levels than healthy volunteers and that this decrease may be corrected by clomipramine.

Adolescent↗
PubMed1983

Determination of the alpha, beta-adrenoceptor blocker YM-09538 in urine by gas chromatography with a nitrogen-sensitive detector.

A gas chromatographic method for the quantitative determination of the alpha, beta-adrenoceptor blocker YM-09538 in urine is described. YM-09538 was extracted from alkalinized urine with ethyl acetate and converted to its cyclic methylboronate derivative. Analysis by gas chromatography using a nitrogen-sensitive detector allowed quantitation of the drug over a concentration range of 0.2-5.0 micrograms/ml. Urinary excretion of YM-09538 was determined in humans after oral administration of 50 mg.

Adrenergic alpha-Antagonists↗
PubMed1998

Somnolence syndrome in adults following cranial irradiation for primary brain tumours.

The purpose of this study was to assess the incidence, pattern and severity of somnolence and fatigue in patients treated with cranial irradiation for primary brain tumours and to identify factors that may influence or mediate symptoms. A detailed prospective study was carried out of 19 patients who received high-dose (45-55 Gy) cranial irradiation as treatment for primary brain tumours. Data were collected for each patient over a 3 month period using a prospective diary utilizing visual analogue scales of common somnolence symptoms and fatigue, and detailed interviews at 2, 6 and 12 weeks following the completion of treatment. Sixteen patients developed somnolence syndrome following treatment. Time series analysis identified a cyclical pattern to the symptoms, with a period of drowsiness and fatigue occurring from day 11 to day 21 and from day 31 to day 35 after radiotherapy. The principal symptoms were those of excessive drowsiness, feeling clumsy, an inability to concentrate, lethargy, being mentally slow and fatigue. Patients treated with accelerated (n = 11) compared with more conventional (n = 8) fractionation experienced more severe drowsiness and fatigue (P < 0.01), although there was no difference in the pattern or the incidence of symptoms. Interview data suggested that patients frequently attributed their symptoms of somnolence to 'flu or other ailments. The unexplained and overwhelming nature of the symptoms was a cause of anxiety. The prospective assessment of symptoms following radiotherapy highlighted a more detailed definition of the symptom complex and pattern of occurrence. Somnolence syndrome is a collection of symptoms consisting of drowsiness, lethargy and fatigue. Forewarning patients and planning supportive management around times of drowsiness and fatigue can help to reduce the anxiety that these symptoms cause.

Adult↗
PubMed2025

Discovery of Isonitrile Lipopeptide Chalkophores from Pathogenic Mycobacteria.

The virulence-associated isonitrile lipopeptide (INLP) biosynthetic gene cluster is conserved across Mycobacterium tuberculosis and many nontuberculous mycobacteria (NTM) pathogens, yet the corresponding mycobacterial metabolites have not been fully characterized, and their biological functions are still debated. Here, we report a precursor neutral loss chromatography based mass spectrometry strategy that enables the targeted discovery of INLPs from Mycobacterium fortuitum, a fast-growing NTM pathogen. By monitoring a characteristic neutral loss of 27.1 Da corresponding to hydrogen cyanide, we identified a family of INLPs directly from bacterial culture extracts. Structural elucidation of a representative compound using NMR and high-resolution MS revealed a distinctive terminal methylated carboxyl group, contrasting with previously reported INLPs bearing linear alcohol, acetal, or cyclic motifs. Bioinformatic analysis and in vitro enzymatic assays identified a methyltransferase encoded within the INLP BGC responsible for methyl ester formation. Furthermore, metal-binding assays demonstrated selective chelation of Cu(I) and Cu(II) by the isolated INLP, but no detectable interaction with Zn(II), suggesting a role in copper homeostasis. These findings represent the first full structural characterization of an INLP from pathogenic mycobacteria, expand our understanding of the enzymes involved in INLP modification, and unequivocally support the copper-binding activity of INLPs from these pathogens.

Lipopeptides↗
PubMed2006

Novel biscapped and monocapped tris(dioxime) Mn(II) complexes: x-ray crystal structure of the first cationic tris(dioxime) Mn(II) complex [Mn(CDOH)3BPh]OH (CDOH2= 1,2-cyclohexanedione dioxime).

This report describes the synthesis and characterization of a series of novel biscapped and monocapped tris(dioxime) Mn(II) complexes [Mn(dioxime)3(BR)2] and [Mn(dioxime)3BR]+ (dioxime = cyclohexanedione dioxime (CDOH2) and 1,2-dimethylglyoxyl dioxime (DMGH(2)); R = Me, n-Bu, and Ph). All tris(dioxime) Mn(II) complexes have been characterized by elemental analysis, IR, UV/vis, cyclic voltammetry, ESI-MS, and, in the cases of [Mn(CDOH)3BPh]OH.CHCl3 and [Mn(CDO)(CDOH)2(BBu(OC2H5))2], X-ray crystallography. It was found that biscapped Mn(II) complexes [Mn(dioxime)3(BR)2] are not stable in the presence of water and readily hydrolyze to form monocapped cationic complexes [M(dioxime)3BR]+. This instability is most likely caused by mismatch between the size of Mn(II) and the coordination cavity of the biscapped tris(dioxime) ligands. In contrast, monocapped cationic complexes [M(dioxime)3BR]+ are very stable in aqueous solution even in the presence of PDTA (1,2-diaminopropane-N,N,N',N'-tetraacetic acid) because of the kinetic inertness imposed by the monocapped tris(dioxime) chelators that are able to completely "wrap" Mn(II) into their N6 coordination cavity. [Mn(CDO)3BPh]OH has a distorted trigonal prismatic coordination geometry, with the Mn(II) being bonded by six imine-N donors. The hydroxyl groups from three dioxime chelating arms form very strong intramolecular hydrogen bonds with the hydroxide counterion so that the structure of [Mn(CDOH)3BPh]OH can be considered as being the clathrochelate with the hydroxide counterion as a "cap".

Cations↗
PubMed2002

Synthesis and characterization of 2,6-Dipp(2)-H(3)C(6)SnSnC(6)H(3)-2,6-Dipp(2) (Dipp = C(6)H(3)-2,6-Pr(i)(2)): a tin analogue of an alkyne.

The reaction of Sn(Cl)C(6)H(3)-2,6-Dipp(2) (Dipp = C(6)H(3)-2,6-Pr(i)()(2)) with a stoichiometric amount of potassium in benzene affords 2,6-Pr(i)()(2)-H(3)C(6)SnSnC(6)H(3)-2,6-Pr(i)()(2) (1) as dark blue-green crystals. The compound 1 is a tin analogue of an alkyne. It was characterized by (1)H and (13)C NMR and UV-vis spectroscopy, cyclic voltammetry, combustion analysis and X-ray crystallography. The structural data show that 1 has a trans-bent, planar C(ipso)SnSnC(ipso) skeleton with a Sn-Sn bond distance of 2.6675(4) A and a Sn-Sn-C angle of 125.24(7) degrees. The Sn-Sn distance, which is ca. 0.15 A shorter than a conventional Sn-Sn single bond, and the trans-bent structure indicate the presence Sn-Sn multiple bond character unlike the related singly bonded ArPbPbAr species.

Journal Article↗
PubMed2003

Thermal and electrochemical C-X activation (X = Cl, Br, I) by the strong Lewis acid Pd3(dppm)3(CO)2+ cluster and its catalytic applications.

The stoichiometric and catalytic activations of alkyl halides and acid chlorides by the unsatured Pd(3)(dppm)(3)(CO)(2+) cluster (Pd(3)(2+)) are investigated in detail. A series of alkyl halides (R-X; R = t-Bu, Et, Pr, Bu, allyl; X = Cl, Br, I) react slowly with Pd(3)(2+) to form the corresponding Pd(3)(X)(+) adduct and "R(+)". This activation can proceed much faster if it is electrochemically induced via the formation of the paramagnetic species Pd(3)(+). The latter is the first confidently identified paramagnetic Pd cluster. The kinetic constants extracted from the evolution of the UV-vis spectra for the thermal activation, as well as the amount of electricity to bring the activation to completion for the electrochemically induced reactions, correlate the relative C-X bond strength and the steric factors. The highly reactive "R(+)" species has been trapped using phenol to afford the corresponding ether. On the other hand, the acid chlorides react rapidly with Pd(3)(2+) where no induction is necessary. The analysis of the cyclic voltammograms (CV) establishes that a dissociative mechanism operates (RCOCl --> RCO(+) + Cl(-); R = t-Bu, Ph) prior to Cl(-) scavenging by the Pd(3)(2+) species. For the other acid chlorides (R = n-C(6)H(13), Me(2)CH, Et, Me, Pr), a second associative process (Pd(3)(2+) + RCOCl --> Pd(3)(2+.....)Cl(CO)(R)) is seen. Addition of Cu(NCMe)(4)(+) or Ag(+) leads to the abstraction of Cl(-) from Pd(3)(Cl)(+) to form Pd(3)(2+) and the insoluble MCl materials (M = Cu, Ag) allowing to regenerate the starting unsaturated cluster, where the precipitation of MX drives the reaction. By using a copper anode, the quasi-quantitative catalytic generation of the acylium ion ("RCO(+)") operates cleanly and rapidly. The trapping of "RCO(+)" with PF(6)(-) or BF(4)(-) leads to the corresponding acid fluorides and, with an alcohol (R'OH), to the corresponding ester catalytically, under mild conditions. Attempts were made to trap the key intermediates "Pd(3)(Cl)(+)...M(+)" (M(+) = Cu(+), Ag(+)), which was successfully performed for Pd(3)(ClAg)(2+), as characterized by (31)P NMR, IR, and FAB mass spectrometry. During the course of this investigation, the rare case of PF(6)(-) hydrolysis has been observed, where the product PF(2)O(2)(-) anion is observed in the complex Pd(3)(PF(2)O(2))(+), where the substrate is well-located inside the cavity formed by the dppm-Ph groups above the unsatured face of the Pd(3)(2+) center. This work shows that Pd(3)(2+) is a stronger Lewis acid in CH(2)Cl(2) and THF than AlCl(3), Ag(+), Cu(+), and Tl(+).

Journal Article↗
PubMed2002

(R)-(+)-palasonin, a cantharidin-related plant toxin, also occurs in insect hemolymph and tissues.

Gas chromatographic and mass spectroscopic analyses of extracts of cantharidin-containing meloid, clerid, and staphylinid beetles revealed the presence of minor to significant amounts of palasonin, previously only known from seeds and fruits of the Indian shrub Buteafrondosa (Leguminaceae). Unlike (S)-(-)-palasonin (> 99% ee) from B. frondosa, the insects produce palasonin of low ee with the (R)-(+)-enantiomer (0-50% ee) prevailing. The ee of palasonin from individual specimens of predatory insects (Trichodes apiarius), which acquire their chemical protection from cantharidin-producing insects, may vary considerably. The absolute configuration of (S)-(-)-palasonin, previously deduced from indirect chemical and spectroscopic methods, was confirmed by X-ray crystal structure analysis of a cyclic imide derived from (S)-(-)-palasonin and (S)-(-)- 1 -(4-nitrophenyl)-ethylamine.

Animals↗
PubMed2005

Mechercharmycins A and B, cytotoxic substances from marine-derived Thermoactinomyces sp. YM3-251.

A new cytotoxic substance named mechercharmycin A was isolated from marine-derived Thermoactinomyces sp. YM3-251. The structure of mechercharmycin A was determined by an X-ray crystallographic analysis to be cyclic peptide-like and bearing four oxazoles and a thiazole. Mechercharmycin B, a linear congener of mechercharmycin A, was also isolated from the same bacterium. Mechercharmycin A exhibited relatively strong antitumor activity, whereas mechercharmycin B exhibited almost no such activity.

Antibiotics, Antineoplastic↗
PubMed2006

The Ni2+O2 reaction: the IR spectrum and structure of Ni2O2. A combined IR matrix isolation and theoretical study.

The formation of Ni2O2 can be observed from the condensation of effusive beams of Ni and O2 in neon or argon matrices. Observation of 58Ni(2)16O2, 58Ni60Ni16O2, 60Ni2(16)O2, Ni(2)18O2 and Ni(2)16O18O isotopic data for five fundamental transitions enable a discussion of structural parameters for matrix-isolated Ni2O2 in its cyclic ground state. Analysis of the nickel isotopic effects on the 58,60Ni2(16)O18O fundamentals suggest an elongated rhombic structure with a Ni-O bond force constant (240+/-10 N m-1) and NiONi bond angles around 79 degrees. The latter points to a Ni-Ni internuclear distance shorter than the O-O one. Low-lying singlet, triplet and quintet states have been studied using density functional theory with an unrestricted wave function and broken symmetry formalism. The high spin states and closed shell singlet states have been also investigated at the CCSD(T) level. The Ni2O2 ground state is calculated to be an antiferromagnetic singlet state with all the hybrid functionals. The first order properties (energies, geometry) calculated with a hybrid functional are very similar when different exchange-correlation functionals with different exact exchange fractions are used and the calculated ground state geometry (NiONi bond angle near 80 degrees, NiO bond distance around 179.5 pm) is in good agreement with the experimental estimate. Nevertheless, a correct reproduction of the experimental vibrational properties is found only when a hybrid functional containing an exact exchange fraction in the 0.4-0.5 range is used. The orbital and topological bonding analyses of Ni2O2 reveal that the relatively short Ni-Ni internuclear distance within the molecule should not be interpreted as a remaining metal-metal bonding interaction, but clearly indicate that the bonding driving force is due to the formation of four strong and highly polarized Ni-O bonds. Even in such an early stage of metal oxidation, the Ni-Ni interaction has virtually disappeared.

Journal Article↗
PubMed2001

Seasonality of birth for cancer in Northern England, UK.

Environmental factors operating around the time of birth may influence the subsequent development of childhood cancer, particularly leukaemia. Certain factors may vary with season (e.g. infections), and we therefore investigated whether there was any evidence of seasonality of month of birth, based on data from 4199 children diagnosed with cancer under the age of 15 years. We extracted details of (i) children born 1960-95 and diagnosed 1968-95 from two population-based registries, covering the Northern (n = 2053) and Yorkshire (n = 1977) Regional Health Authority and (ii) children born in Cumbria 1950-93 and diagnosed anywhere in the UK before 1994 from a birth cohort database (n = 397). The following diagnostic categories were analysed: 0-14 years--all cancers, leukaemias, acute lymphoblastic leukaemias, central nervous system tumours, all other solid tumours; 1-6 years--leukaemias, acute lymphoblastic leukaemias. Seasonal variation was tested using Walter and Elwood's test, and logistic regression analysis allowing for cyclical variation in month of birth. No evidence of seasonality was present for any group except acute lymphoblastic leukaemia diagnosed among 1- to 6-year-olds. Seasonal trends varied by region: in the Northern and Cumbrian datasets, seasonality patterns were significant and similar (P < 0.05) with a predicted peak in early spring, whereas in Yorkshire there was less strong evidence of seasonality (P = 0.08) with a peak predicted in late summer. These findings suggest that local seasonal environmental factors operating around the time of birth are not associated with the totality of childhood cancer, but possible links with acute lymphoblastic leukaemia are supportive of a hypothesis of an infectious aetiology.

Adolescent↗
PubMed2001

An analysis of 6 decades of hygiene-related advertising: 1940-2000.

OBJECTIVES: To describe and analyze trends in hygiene-related advertisements and examine potential social and regulatory changes that might be associated with these trends. METHODS: From 1940 to 2000, advertisements in January issues of 2 widely read magazines were analyzed every fifth year, and 2 additional magazines only available from 1960 to 2000 were also analyzed every fifth year. In a content analysis, the total number of advertisements were determined and specific advertisements were grouped into categories (personal hygiene, dishwashing, laundry, and house cleaning) and further examined for the presence of 4 key claims (aesthetics, health effects, time-saving, and microbial effects). RESULTS: From 1940 to 2000 for all magazines combined, 10.4% of the advertisements were devoted to hygiene products. After 1960 there were significantly fewer hygiene advertisements as compared with 1940 to 1955, and there was a significant increase after 1980 (P <.00001). Throughout all 6 decades, most advertisements related to personal hygiene. There were no significant differences over time in the proportion of advertisements that made claims related to health, microbial effects, or aesthetics, but significantly more advertisements before 1960 made time-savings claims (P =.009). CONCLUSIONS: This content analysis reflects a cyclical attention in consumer advertising to personal and home hygiene products during the past 6 decades, with a waning of interest in the decades from 1960 to 1980 and an apparent resurgence of advertisements from 1985 to 2000. The potential contributions of federal regulatory bodies and societal changes (e.g., new marketing strategies and options, product development, new and re-emerging infectious diseases, increasing concern about antimicrobial resistance, and increasing recognition that infectious diseases are unlikely to be eradicated) to these marketing trends are discussed.

Advertising↗
PubMed1971

Conformation of cyclolinopeptide a observed by circular dichroism.

A stereochemical investigation, by circular dichroism, of a synthetic nonapeptide (cyclolinopeptide A) in several organic and organic-sulfuric acid solvents is presented. From this examination, and results found for a conformationally rigid model compound, 1,7,7-trimethyl-3-azabicyclo [2.2.1] heptan-2-one(camphorolactam), it is concluded that cyclolinopeptide A may exist in several conformations in solution. None of these conformations is believed to be stabilized by intramolecular hydrogen bonds. Some details on an x-ray analysis of the cyclic nonapeptide are also presented.

Journal Article↗
PubMed1981

Obligatory separation of hormone binding and biological response curves in systems dependent upon secondary mediators of hormone action.

A mathematical model is presented that describes the effects of hormone concentration on receptor saturation and biological response in systems dependent upon the generation of a secondary mediator such as cyclic AMP. The analysis makes the following assumptions: (i) the binding of hormone to its receptor is a reversible, second-order reaction; (ii) the concentration of mediator that is generated is directly proportional to the number of membrane binding sites occupied by hormone; and (iii) the binding of the mediator with its intracellular receptor to generate an effector complex is also second-order and results in a proportionate biological response. It follows from this treatment that the hormone concentration required for half-maximal biological response is formally lower than that required for half-maximal receptor saturation and that the difference between these two concentrations will depend upon the ratio of total mediator generated at full receptor occupancy to the dissociation constant of the mediator with its receptor. Without invoking concepts of negative cooperativity, this model offers a simple explanation for discrepancies between receptor occupancy and biological response curves that are often observed. Moreover, the mathematical form of the predicted biological response curves conforms to the shape of the response curves observed experimentally in a wide variety of systems.

Animals↗