Total synthesis of heterocyclic steroids,part IV: Mass spectrometry in stereochemical determination of the C/D ring fusion geometry in some heteroaromatic steroids

The mass spectral fragmentation pattern and the relative intensities of the fragment peaks of the D ring in some 8-dehydroheteroaromatic steroids were studied. Characteristic differences for the $\text{cis and trans}$ isomers were ascertained and were used for the determination of the stereochemistry of thiasteroids of which only one isomer was obtained.     

Side chain azasteroids and thiasteroids as sterol methyltransferase inhibitors in ergosterol biosynthesis

The synthesis of some novel azasteroids and thiasteroids based on a pregnan nucleus with a Δ7 double bond in two to five steps from the key aldehyde (3S,20S)-20-formylpregn-7-en-3-yl acetate has been disclosed herein. These compounds were evaluated as potential inhibitors of the enzyme Δ24-sterol methyltransferase (24-SMT), which is a key enzyme in the biosynthesis of ergosterol, and for their effects on the growth of the yeast Yarrowia lipolytica. Most of the side chain modified analogues were recognized as 24-SMT inhibitors, and in particular the 23-azasteroids 5f–5i and the 24-azasteroid 11 showed potent antifungal activity. The target enzyme could be identified unambiguously using an improved whole-cell assay combined with GC–MS analysis of the sterol pattern resulting upon incubation with the inhibitors.     

Characteristics of Symmetric Surface Plasmon Polariton Mode in Glass–Metal–Glass Waveguide

The propagation characteristics of symmetric surface plasmon polariton mode in a glass–metal–glass waveguide are presented. Gallium lanthanum sulfide has been taken as the glass and silver (Ag) has been used as the metal. The analysis has been done both numerically and analytically. A two-dimensional finite-difference time-domain-based simulation model has been developed in order to analyze the propagation characteristics numerically. The obtained results using numerical and analytical methods have been compared and a very good agreement has been found.     

Imaging erythrocytes under physiological conditions by atomic force microscopy

Since its invention in the mid 1980s atomic force microscopy has revolutionised the way in which surfaces can be imaged. Close to atomic resolution has been achieved for some materials and numerous images of molecules on surfaces have been recorded. Atomic force microscopy has also been of benefit to biology where protein molecules on surfaces have been studied and even whole cells have been investigated. Here we report a study of red blood cells which have been imaged in a physiological medium. At high resolution, the underlying cytoskeleton of the blood cell has been resolved and flaws in the cytoskeleton structure may be observed. Comparison of the normal 'doughnut' shaped cells with swollen cells has been undertaken. Differences in both the global properties of the cells and in the local features in cytoskeleton structure have been observed.     

Productivity improvement in xanthan gum fermentation using multiple substrate optimization

A novel and more comprehensive formulation of the optimal control problem that reflects the operational requirements of a typical industrial fermentation has been proposed in this work. This formulation has been applied to a fed-batch bioreactor with three control variables, i.e., feed rates of carbon source, nitrogen source, and an oxygen source, to result in a 148.7% increase in product formation. Xanthan gum production using Xanthomonas campestris has been used as the model system for this optimization study, and the liquid-phase oxygen supply strategy has been used to supply oxygen to the fermentation. The formulated optimization problem has several constraints associated with it due to the nature of the system. A robust stochastic technique, differential evolution, has been used to solve this challenging optimization problem. The infinite dimensional optimization problem has been approximated to a finite dimensional one by control vector parametrization. The state constraints that are path constraints have been addressed by using penalty functions and by integrating them over the total duration to ensure a feasible solution. End point constraints on final working volume of the reactor and on the final residual concentrations of carbon and nitrogen sources have been included in the problem formulation. Further, the toxicity of the oxygen source, H(2)O(2), has been addressed by imposing a constraint on its maximum usable concentration. In addition, the initial volume of the bioreactor contents and feed concentrations have been handled as decision variables, which has enabled a well-grounded choice for their values from the optimization procedure; adhoc values are normally used in the industry. All results obtained by simulation have been validated experimentally with good agreements between experimental and simulated values.     

Photomyoclonic seizures in the baboon, Papio papio.

The inborn seizure response of Papio papio to intermittent light stimulation has been reviewed as a model of human epilepsy. The electrographic and clinical features have been described and useful methodology has been outlined. A diurnal cyclicity in seizure responsiveness has been described with greatest seizure severity at 8 AM in parallel with a rise in urinary output of cortisol. Hormonal influences on the seizure response have been described for ethinyl estradiol, thyroxin, and triiodothyronine. Evidence regarding neurotransmitter involvement has been reviewed. Data regarding use of the animal for anticonvulsant testing in single and chronic doses has been discussed. Particular advantages of the model for study of age-related drug effects and the assessment of the effects of chronically administered anticonvulsant agents on learning and memory have been described.     

Cloning, mapping and gene product identification of rhaT from Escherichia coli K12

Rhamnose utilization requires the function of a specific rhamnose transport system. Rhamnose transport mutants have been isolated and characterized. The structural gene, rhaT, encoding the rhamnose permease has been cloned from Escherichia coli. rhaT has been mapped in the rha locus (87.7 min) by analysis of cotransduction with glpK and other rha markers. The precise location of the gene has been determined by complementation analysis of rhamnose transport mutants transformed with recombinant plasmids containing different fragments of the cloned region. Gene order (counterclockwise) is established as glpK . . . rhaT-rhaR-rhaS-rhaB-rhaA-rhaD. The gene product has been identified by expression of rhaT in a T7 RNA polymerase/promoter system. This 23 kDa protein has been assigned to the rhaT product and has been shown to be located in the cell membrane.     

Study of a comparative statistical analytical model for nucleotide sequences in the genome of viruses of the Papovaviridae family

In the present study a model for comparative analysis of nucleotide sequences has been developed, in order to evaluate statistical features of nucleotide distribution in DNA strands without any genetic relationship. Every DNA strand has been considered as a finite Markov chain; a matrix, whose elements represent the number of couplings between a nucleotide and the following one in 5'-3' direction, has been used for every DNA strand, and the statistical relationship has been detected by using Kendall's test. The genomes of Polyomavirus (strain A2) and DPV have been analysed by the proposed model; a substantial likeness between the behaviour of nucleotide distribution on all four DNA strands analysed has been shown; the strongest likeness concerned the complementary strands of Polyomavirus as well as the homologous sense strands of both viruses.     

pH-sensitive hydrogel based on a novel photocross-linkable copolymer

A pH sensitive hydrogel has been prepared by a UV irradiation technique. Starting polymer was the PHM (poly hydroxyethylaspartamide methacrylated) obtained from polyaspartamide (PHEA) partially derivatized with methacrylic anhydride (MA). This new copolymer has been further derivatized with succinic anhydride (SA) to obtain PHM-SA that has been cross-linked by UV irradiation to form a pH sensitive hydrogel. The network, recovered after washing as a powder, has been been characterized by FT-IR spectrophotometry and particle size distribution analysis. Moreover, to have information about water affinity of the prepared sample, swelling measurements have been carried out in aqueous media mimicking biological fluids. The possibility to employ the prepared hydrogel as a pH-sensitive drug delivery system (DDS) has been investigated. In particular, ibuprofen ((S)(+)4-isobutyl-alpha-methylphenyl-acetic acid), chosen as a model drug, has been entrapped into the PHM-SA hydrogel, and in vitro release studies have showed that its release rate depends on different swelling of the network as a function of the environmental pH.     

Methods of Therapy in Alcoholism

Although the philosophy of the community mental health center has been applied to alcoholism since the early part of this decade, it has been pursued much more intensively in recent years, and there has been a decentralization in the management of alcoholics in a series of stages from the jail or work-house to the state hospital and to the clinic and the community. The medical practitioner now has opportunity to treat the alcoholic in private practice.Advances have been made in two directions. Advances in medical management have included reinforcement of the importance of hydration and electrolyte balance, particularly magnesium. Psychopharmacology has contributed three drugs particularly important in the management of acute alcoholism and its complications. These drugs are chlordiazepoxide, chlorpromazine, and thioridazine. Another drug, Antabuse, when properly used, has proven extremely valuable as a deterrent.Equally important have been administrative advances. The importance of the environment and its manipulation has been recognized, and a series of institutional and non-institutional resources, such as clinics, half-way houses, foster homes, and Alcoholics Anonymous has made it less likely that a patient will be turned away without help.     

Morphometric analysis of the state of the intramural nervous apparatus of rat duodenum]

Structural organization of the intramural apparatus of the duodenum has been studied in normal white rats. By means of a planimeter, the area of the nerve cells and their nuclei has been estimated in serial sections of the cranial and caudal parts of the duodenum; a definite regularity on the nerve cell types distribution has been stated in different parts of the duodenum. Concentration of afferent nerve elements has been noted in the cranial part of the duodenum.     

Melanocyte-directed enzyme prodrug therapy (MDEPT): development of a targeted treatment for malignant melanoma.

A novel prodrug rationally designed to function as a tyrosinase substrate has been synthesised to allow targeted treatment of malignant melanoma. This agent has been evaluated for tyrosinase-mediated drug release, and has been shown to act in the desired manner. Furthermore, differential cytotoxicity has been demonstrated in cell lines which express tyrosinase and those which do not.     

Persistence of bacterial pathogens as a physiological phenomenon

The complex ecosystem of humans and microbes has been presented as an associative symbiosis based on a mutual support of symbionts with different consequences for them. Conditions for the persistence of bacteria have been defined: their resistance to environmental factors, antagonism in biocenosis, and stability to withstand host defense mechanisms. The key role of bacterial peptidoglycan has been defined for their survival in an infected organism, and the classification for persistent mechanisms of pathogens has been given. The group of bacterial secreted protease providing microbial resistance to defense factors of the organism has been described. Host colonizing resistance has been presented as a physiological regulatory system controlling bacterial penetration into an organism. Regulatory mechanisms for bacterial persistence have been discussed.     

Mechanism of prolactin action

Most experimental information regarding the mechanism of action of prolactin in its diverse array of target tissues has been discovered using mammary tissues. Evidence has recently been presented that suggests that prolactin may be "internalized" into its target cells and have intracellular actions. Accordingly, it has been reported that prolactin stimulates RNA synthesis in isolated nuclei from mammary tissues; and by immunoflorescent studies, prolactin has been located within its target cells. It has been further suggested from additional experimental studies that the primary action of prolactin may involve its initial interaction with fixed plasma membrane receptor sites. Subsequent actions of prolactin may involve the following: a) an increased intracellular concentration of potassium and a reduced level of sodium, b) an increased level of cGMP and a reduced level of cAMP, c) an enhanced rate of prostaglandin biosyntheesis mediated by a stimulation of phospholipase A2 activity, and d) a stimulation of polyamine synthesis. It has also been shown that the actions of prolactin require calcium ions in the extracellular environment. Laboratory studies have thus indicated that the actions of prolactin may be carried out by a number of processes; but a single, primary action of this hormone that accounts for all of its actions has not yet been proven.     

CESAREAN SECTION EXPERIENCE AT THE UNIVERSITY OF CALIFORNIA HOSPITAL

A review of the 746 cesarean sections performed at the University of California Hospital from 1907 through 1948 shows an overall cesarean section incidence of 3.91 per cent. The maternal mortality rate associated with these cesarean sections has been 1.61 per cent. There has been a steady decline in mortality over the 40-year period and there have been no deaths from cesarean section in the last ten years. The over-all incidence of morbidity associated with cesarean section has been 40.5 per cent and again there has been a significant improvement in recent years. The fetal mortality associated with cesarean section has been 6.1 per cent. In view of recent experience, standards based on figures collected 20 years ago are no longer tenable.     

Adenylate cyclase of the causative agent of plague: its purification and properties

Three forms of adenylate cyclase have been detected in Y. pestis: membrane-bound, cytoplasmic and extracellular. Extracellular adenylate cyclase has been purified so as to achieve a homogeneous state, and some of its physicochemical parameters have been investigated. In the process of purification the initial preparation of this enzyme has been subjected to heating at 100 degrees C for 15 minutes, fractionation with ammonium sulfate, and gel filtration on Sephadex G-100. The homogeneity of adenylate cyclase has been confirmed by electrophoresis in 7.5% polyacrylamide gel and precipitation by the plague agglutinating serum. The enzyme has been found to have a molecular weight of 30,000 daltons and to show the optimum activity at pH 7.0-7.2 and at a temperature between 37 and 40 degrees C. Monospecific rabbit serum to the homogeneous preparation of adenylate cyclase has been obtained.     

Mapping of phase response properties of monopolar ECG voltages

In the present investigation an attempt has been made to study the phase response properties of monopolar chest lead ECG voltages. Using a generator model of the heart an equivalent circuit of ECG network has been developed. The equivalent impedance between WCT and probe electrode has been determined by reduction techniques. From this equivalent impedance the phasor characteristics of monopolar ECG voltages have been analysed for change in probe electrode locations. The source of the generated voltage, i.e., the heart, will develop a different voltage for its different condition. There will also be a change in impedances. Thus for the normal subject the distribution of the phasor of the ECG voltages will be different from that of the abnormal one. A software tool has been developed to evaluate the relative phase response of ECG voltages. The data acquisition of monopolar ECG records of chest leads V1 to V6 from chart recorder has been done with the help of AutoCAD application package. The harmonic constituents of ECG voltages have been evaluated at each harmonic plane and the phase characteristics have been studied in polar coordinate for normal subjects as well as for a typical case. An interesting result has been observed in typical cases which are indicated in the paper.     

The organization of capsaicin-sensitive visceral afferent systems

It has become clear that a number of neuropeptides are found in sensory nerves, some of which have been identified in visceral afferents. The best studied peptide is substance P, which has been localized in a population of capsaicin-sensitive visceral afferents. It has been established that there are a varied proportion of substance P-containing afferents in different visceral structures. In general, the peripheral termination of these nerves is around blood vessels. The central terminations of visceral afferents are in laminae I and V in the dorsal horn of the spinal cord. Substance P has been localized in these laminae and appears to be capsaicin-sensitive and therefore of sensory origin. Recently, substance K, which is derived from the same gene as substance P, has been found in visceral structures. Calcitonin gene-related peptide has been found in certain viscera to be contained in capsaicin-sensitive nerves. The contribution that other peptides make to visceral afferent innervation is not known.     

Interactions in a mixed bacterial population growing on methane in continuous culture

The growth of a mixed methane-utilizing culture in a continuous flow fermenter has been studied under both methane and oxygen limitation. Small additions of methanol have been shown to inhibit the methane-utilizing moiety in the culture and it has been shown that the Hyphomicrobium sp. in the mixed culture removes any inhibitory methanol. The interaction between the methane-utilizing Pseudomonas sp., and the Hyphomicrobium sp. has been explained and a model of the continuous mixed culture under oxygen limitation has been formulated. Qualitative predictions of transient phenomena by the model have been verified experimentally.