Acute phase reactants in leprosy.

Serum levels of C-reactive protein (CRP) and plasma levels of fibronectin (Fn) were studied in 74 untreated leprosy patients. CRP was detected by latex agglutination in 25.6% of the patients. A significant increase in Fn levels was seen in all the groups of leprosy patients, as compared to the controls.     

Solid phase synthesis of quinolones.

Solid phase syntheses of ethyl 6-carboxyquinol-4(1H-)-one-3-carboxylate (5) and N-substituted 6-carboxyquinol-4(1H)-one-3-carboxamides 7a-d have been described. Antifilarial in vitro activities of 5,7a-d against Brugia malayi have also been delineated.     

Solid phase synthesis of polynucleotides. VIII. Synthesis of mixed oligodeoxyribonucleotides by the phosphotriester solid phase method.

A solid phase method for the simultaneous synthesis of mixed oligonucleotides using a phosphotriester approach has been developed. For this synthesis, a mixture of mono or dimeric coupling units is used, and a slight difference in the reactivity of those units is found. However, this difference does not hamper the simultaneous, mixed oligonucleotide synthesis, and the sequence analysis of a product demonstrates the existence of all desired sequences in the final mixture.     

Evidence for phase boundary lipid. Permeability of Tempo-choline into dimyristoylphosphatidylcholine vesicles at the phase transition.

The existence of distinct regions of mismatch in molecular packing at the interfaces of the fluid and ordered domains during the phase transition of dimyristoylphosphatidylcholine vesicles has been demonstrated by measuring the temperature dependence of the permeability to a spin-label cation and comparing this with a statistical mechanical calculation of the fraction of interfacial lipid. The kinetics of uptake and release of the 2,2,6,6-tetramethylpiperidinyl-1-oxycholine (Tempo-choline) spin label by single-bilayer dimyristoylphosphatidylcholine vesicles were measured using electron spin resonance spectroscopy to quantitate the amount of spin label present within the vesicles after removal of the external spin-label by ascorbate at 0 degrees C. Both the uptake and release experiments show that the Tempo-choline permeability peaks to a sharp maximum at the lipid-phase transition, the vesicles being almost impermeable to Tempo-choline below the transition and having a much reduced permeability above. The temperature profile of the permeability is in reasonable quantitative agreement with calculations of the fraction of interfacial boundary lipid from the Zimm and Bragg theory of cooperative transitions, which use independent spin-label measurements of the degree of transition to determine the cooperativity parameter. The relatively high intrinsic permeability of the interfacial regions (P approximately 0.2-1.0 X 10(-8) cm/s) is attributed to the mismatch in molecular packing of the lipid molecules at the ordered-fluid boundaries, which could have important implications not only for permeability in natural membranes (e.g., in transmitter release), but also for the function of membrane-bound enzymes and transport proteins.     

Frequency domain impedance measurements of erythrocytes. Constant phase angle impedance characteristics and a phase transition.

We report measurements of the electrical impedance of human erythrocytes in the frequency range from 1 Hz to 10 MHz, and for temperatures from 4 to 40 degrees C. In order to achieve high sensitivity in this frequency range, we embedded the cells in the pores of a filter, which constrains the current to pass through the cells in the pores. Based on the geometry of the cells embedded in the filter a circuit model is proposed for the cell-filter saline system. A constant phase angle (CPA) element, i.e., an impedance of the form Z = A/(j omega)alpha, where A is a constant, j = square root of -1, omega is angular frequency, and 0 less than alpha less than 1 has been used to describe the ac response of the interface between the cell surface and the electrolyte solution, i.e., the electrical double layer. The CPA and other elements of the circuit model are determined by a complex nonlinear least squares (CNLS) fit, which simultaneously fits the real and imaginary parts of the experimental data to the circuit model. The specific membrane capacitance is determined to be 0.901 +/- 0.036 microF/cm2, and the specific cytoplasm conductivity to be 0.413 +/- 0.031 S/m at 26 degrees C. The temperature dependence of the cytoplasm conductivity, membrane capacitance, and CPA element has been obtained. The membrane capacitance increases markedly at approximately 37 degrees C, which suggests a phase transition in the cell membrane.     

alpha-DNA. VII. Solid phase synthesis of alpha-anomeric oligodeoxyribonucleotides.

An efficient procedure for the synthesis of unnatural alpha-anomeric oligodeoxyribonucleotides is described. This solid-phase procedure is based on the use of alpha-nucleoside phosphoramidites and alpha-nucleoside derivatized solid supports corresponding to the four natural bases and allow rapid synthesis of oligonucleotides up to 20 alpha-deoxynucleotide units in length. After HPLC purification, a 15-mer: alpha-d(CCTCTCGTTCTTTAC) and a 20-mer: alpha-d(ATACTTGAGGAAGAGGTGTT) were obtained respectively in 27 and 29% overall yields. Their purity, nucleoside composition and primary structure were ascertained by HPLC and Maxam-Gilbert sequence analyses.     

Enzyme purification using temperature-induced phase formation.

A new type of aqueous two-phase system composed of an ethylene oxide and propylene oxide random co-polymer, UCON 50-HB-5100, as the upper phase polymer and either dextran or hydroxypropyl starch as the lower phase polymer has been characterized and used to purify 3-phosphoglycerate kinase (EC 2.7.2.3) and hexokinase (EC 2.7.1.1) from bakers' yeast. The UCON 50-HB-5100 polymer has a cloud point of 55 degrees C at which temperature it phase separates from water. This cloud point can be lowered to 40 degrees C by the addition of 0.2 M sodium sulfate salt. The low cloud point of this UCON polymer makes it possible to obtain the target enzymes in a water and buffer solution, and to recover and recycle the UCON 50-HB-5100 polymer. The phase diagrams for the systems UCON 50-HB-5100/Dextran T500 and UCON 50-HB-5100/hydroxypropyl starch have been determined. Yeast homogenate was first partitioned in a system composed of a top phase containing UCON 50-HB-5100 and a bottom phase containing either dextran or hydroxypropyl starch. The top phase containing the enzyme free of cell debris was removed and the temperature increased above the cloud point of the UCON until a new two phase system composed of water as the top phase and a concentrated liquid UCON 50-HB-5100 bottom phase was formed. The water phase containing the enzyme was removed and the bottom phase containing the UCON 50-HB-5100 could be recycled to perform a second extraction.     

Liquid phase parallel synthesis of guanidines.

Combinatorial synthesis of N,N'-di(Boc)-Protected guanidines containing piperazine and pyrrolidine scaffolds has been developed. We initiate a preliminary study on the reactivity of several guanylating reagents with soluble polymer-bound diamines in liquid phase. Guanidines are liberated from the polymer support under mild conditions in high yields and high purity by simple precipitation and washings. This combinatorial liquid-phase methodology proves to be a useful tool for constructing guanidine libraries containing diamine scaffolds.     

Luteal phase immunosuppression and meat eating.

Immunosuppression during pregnancy makes the mother vulnerable to pathogens. Because meat is the principal source of ingestible pathogens, pregnancy raises the costs of meat eating. Natural selection has crafted a mechanism involving changes in nausea susceptibility and olfactory perception that reduces meat consumption during pregnancy. Evidence is presented showing that the luteal phase is marked by both immunosuppression and changes in nausea susceptibility and olfaction; meat consumption may be reduced during this period, suggesting a mechanism similar to pregnancy sickness. Constraints on compensatory increases in meat consumption outside of the luteal phase explain why women eat less meat than men. Meat is the principal target of acquired aversions. Women possess more aversions than men, suggesting that prophylactic mechanisms sometimes result in longstanding dietary changes. Reproductive immunosuppression explains many aspects of dietary behavior and sheds light on factors that may have contributed to gender-based divisions of labor during hominid evolution.     

Diabetic cardiomyopathy: the preclinical phase.

Left ventricular function was assessed by measuring sytolic time intervals in insulin-requiring diabetics with and without significant microangiopathy. The results were compared with those in normal controls. Significant microangiopathy was defined as proteinuria over 3 g/24 h or proliferative retinopathy. Left ventricular function was also assessed one and a half years later by echocardiography in four patients with microangiopathy. Patients with angina, previous myocardial infarction, hypertension, and alcoholism were excluded. All had normal electrocardiograms and chest radiographs. Diabetics with microangiopathy had impaired left ventricular function, whereas those with uncomplicated diabetes had normal function. This finding supports the existence of a specific diabetic cardiomyopathy due to microangiopathy rather than the metabolic defect. The association of microangiopathy and impaired left ventricular function may explain the high immediate mortality and the high incidence of cardiogenic shock and congestive heart failure after myocardial infarction in diabetics.