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Host-parasite relations in cotton rat filariasis. III. The quantitative transmission of Litomosoides carinii to un-irradiated and irradiated golden hamsters and white mice.

The quantitative transmission of Litomosoides carinii by Liponyssus bacoti to un-irradiated and irradiated hamsters and mice is described. Both young and adult, un-irradiated and irradiated hamsters were highly susceptible to L. carinii but mice (un-irradiated or irradiated) were poor hosts. All hamsters (18 un-irradiated and seven irradiated) became infected. Seven out of nine mice in an un-irradiated series became infected. There was apparently 'age resistance' or 'young susceptibility' in the hamsters. The susceptibility of young hamsters appeared similar to that of new-born Carworth white rats and cotton rats. The pattern of infection in un-irradiated and irradiated hamsters was similar. Results from irradiated animals were insufficient to draw any clear conclusions on the effect of irradiation to susceptibility to infection with L. carinii. X-irradiation apparently did not affect the innate susceptibility cr resistance of hamsters and mice to worms. The duration and intensity of microfilaraemia was apparently higher in irradiated hamsters.

Animals

UN-1, a murine monoclonal antibody recognizing a human thymocyte undescribed antigen.

A monoclonal antibody (MoAb), UN-1, specific for a human thymocyte cell surface antigen was produced. The same MoAb recognized in immunofluorescence also cells of the human T line HPB-ALL, while did not bind human peripheral blood cells and cells of some T, B and myeloid lines. Western blotting analysis of thymocyte membranes with MoAb UN-1 revealed a structure with a molecular weight of 150 kDa. Therefore both the pattern of expression and the size of the antigen recognized by MoAb UN-1 did not correspond to any previously described cell surface molecule.

Animals

Swedish UN soldiers in Cyprus, UNFICYP: their psychological and social situation.

Two Swedish rifle batallions serving as UN soldiers in Cyprus (UNFICYP) have been investigated with respect to their demographic background and motives for application for UN service. The comparison of symptoms of stress in general, of posttraumatic stress disorder specifically, and some other variables of reaction with various studies of Swedish UN soldiers in different settings has given the following results. Very few interviewees experienced 'personal nervous breakdown' (0.5%). The soldiers reported in general very few psychological or psychosomatic complaints in the short time perspective. There seemed, however, to be two groups of persons at risk, namely those who were repatriated and those with a high consumption of alcohol.

Adult

Un-cross-matched blood for emergency transfusion. One year's experience in a civilian setting.

One year's experience (56 cases) in the use of un-cross-matched blood for emergency transfusion in a large civilian teaching hospital showed that 49 transfusions were given as un-cross-matched, group-specific (ABO and Rh) blood in emergencies. Seventy-seven percent (43) of blood requests were for patients with trauma, unexpected massive intraoperative hemorrhage, or ruptured aneurysm. The indications for emergency transfusion were questionable in ten cases. There were no adverse effects noted even though complete serologic testing had not been done. While the use of un-cross-matched blood is usually safe, the potential for serious reaction exists. Overuse should be discouraged.

ABO Blood-Group System

Quantitative analyses of hydrophobicity of di- to pentapeptides having un-ionizable side chains with substituent and structural parameters.

With experimental conditions established recently, we measured the partition ratio (P') of 124 di- to pentapeptides composed of amino acids having un-ionizable side chains in a 1-octanol:pH 7.0 aqueous phosphate buffer system as an approximate zwitterionized "molecular" partition coefficient (P). Empirical equations of good quality, correlating the variations in log P' value of peptides with free energy-related physicochemical parameters for the side chain substituents and substructures, were formulated. The significant side chain parameters were those representing the intrinsic hydrophobicity, the steric effect on the relative solvation of functional groups on the backbone, and the conformational potential index derived from the Chou-Fasman beta-turn potential parameters. For polar side chains, specific indicator variables were required for intramolecular hydrogen-bond formations and the "polar proximity effect" for reductions of hydrophilicity observed when polar groups are crowded together. The proline residue was shown to contribute to the log P' value depending not only on its location on the backbone but also on the number of residues in peptides. On the basis of the analyses, we proposed a new "effective" hydrophobicity index for un-ionizable side chains which could predict the secondary structure of oligopeptides.

Algorithms

pH gradients across phospholipid membranes caused by fast flip-flop of un-ionized fatty acids.

A central, unresolved question in cell physiology is how fatty acids move across cell membranes and whether protein(s) are required to facilitate transbilayer movement. We have developed a method for monitoring movement of fatty acids across protein-free model membranes (phospholipid bilayers). Pyranin, a water-soluble, pH-sensitive fluorescent molecule, was trapped inside well-sealed phosphatidylcholine vesicles (with or without cholesterol) in Hepes buffer (pH 7.4). Upon addition of a long-chain fatty acid (e.g., oleic acid) to the external buffer (also Hepes, pH 7.4), a decrease in fluorescence of pyranin was observed immediately (within 10 sec). This acidification of the internal volume was the result of the "flip" of un-ionized fatty acids to the inner leaflet, followed by a release of protons from approximately 50% of these fatty acid molecules (apparent pKa in the bilayer = 7.6). The proton gradient thus generated dissipated slowly because of slow cyclic proton transfer by fatty acids. Addition of bovine serum albumin to vesicles with fatty acids instantly removed the pH gradient, indicating complete removal of fatty acids, which requires rapid "flop" of fatty acids from the inner to the outer monolayer layer. Using a four-state kinetic diagram of fatty acids in membranes, we conclude that un-ionized fatty acid flip-flops rapidly (t1/2 < or = 2 sec) whereas ionized fatty acid flip-flops slowly (t1/2 of minutes). Since fatty acids move across phosphatidylcholine bilayers spontaneously and rapidly, complex mechanisms (e.g., transport proteins) may not be required for translocation of fatty acids in biological membranes. The proton movement accompanying fatty acid flip-flop is an important consideration for fatty acid metabolism in normal physiology and in disease states such as cardiac ischemia.

Biological Transport

Molecular characterization of the p(un) allele of the mouse pink-eyed dilution locus.

The mouse pink-eyed dilution locus, p, located on chromosome 7, mediates coat and eye color. The human correlate of this gene may underlie some forms of tyrosinase-positive oculocutaneous albinism. Mutations at the p locus result in a reduction in pigmentation of the eyes and coat. Although most mutant p alleles (including all spontaneous mutations) affect only pigmentation, several mutant alleles (all radiation induced) are also associated with a variety of other phenotypes. We have focused our attention on the p(un) mutant allele, a spontaneous mutation, exhibiting one of the highest reversion frequencies reported for a mammalian mutation. Using a new technique, genome scanning, we have cloned fragments of genomic DNA from the p locus that are associated with a DNA duplication in p(un) DNA. These fragments can now be used to locate the p gene-encoding sequences and aid in the molecular characterization of complex mutant p alleles.

Albinism, Oculocutaneous

[Synthesis and antiinflammatory and anticancer activities of 2-(E)-(un)substituted benzylidene cyclopentanones and their Mannich base hydro chlorides].

It has been known that non-steroidal antiinflammatory drugs (NSAIDs) act by preventing cyclooxygenase products of arachidonic acid. In recent years, research on non-steroid dual inhibitors of cyclooxygenase (CO) and 5-lipoxygenase (5-LO), which should represent a novel class of antiinflammatory drugs with a wider spectrum of activity than classical NSAIDs, has been carried out. In the present paper, a total of 29 compounds including 18 compounds of 2-(E)-(un) substituted benzylidene cyclopentanone (I) derivatives and 11 compounds of 2-(E)-(un)substituted benzylidene-5-dimethylaminomethyl cyclopentanone (II) derivatives were synthesized as dual inhibitors of CO/5-LO. Preliminary pharmacological test showed that I4, I12 and I13 given orally have significant inhibiting effect on carrageenan induced rat paw edema and most compounds of type II exhibited potent effect when given subcutaneously. In particular, II3, which inhibited by 95.8%, 70.34%, and 44.2% at 50, 25, and 12.5 mg/kg respectively, was similar to Ibuprofen. Some compounds of type II exhibited anticancer activity both in vitro (IC50 ranging from 2.93 to 18.06 mumol/L on L1210) and in vivo (maximum increase of life span was 97.5% on EAC in mice).

Animals

Immunoglobulin prophylaxis against hepatitis A among Swedish UN soldiers in an endemic region.

Six hundred and fifteen Swedish soldiers (X = 24.9 years) serving with the UN forces in Cyprus were tested for antibody against hepatitis A (anti-HAV) before and after six months' service. Before the service, a high susceptibility to hepatitis A was found, as only 2.3% (14/615) had anti-HAV. In comparison, the prevalence of anti-HAV among 124 native Cypriots (X = 23.9 years) was 97% (120/124), which showed Cyprus to be a region where hepatitis A is endemic. The soliders were given immunoglobulin (IG) prophylaxis (2 ml of 16.5% IG) against hepatitis A very third month. The incidence of subclinical seroconversion against hepatitis A among the Swedish soliders was 0.2% (1/615). It was concluded that the IG-prophylaxis scheme used seems to be highly effective and probably completely prevents even subclinical seroconversion against hepatitis A in non-immune persons in regions where hepatitis A is endemic.

Adolescent

Polyamine spider toxins are potent un-competitive antagonists of rat cortex excitatory amino acid receptors.

We examined the effect of argiopine and argiopinine 3, low molecular weight polyamine venom components of the spider Argiope lobata, on rat cortical excitatory amino acid (EAA) receptors expressed in Xenopus oocytes. Responses to 100 microM N-methyl-D-aspartate (NMDA) with 10 microM glycine were blocked by both of the polyamine toxins in a dose-dependent manner. Both compounds had similar potencies against 100 microM kainate or 50 microM (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (L-AMPA). Oscillatory responses to 2 microM quisqualate were unaffected by either polyamine toxin. Increasing concentrations of either NMDA, kainate or AMPA were unable to overcome the antagonism by either spider toxin. We were able to demonstrate a use-dependent phenomenon similar to that of phencyclidine; neither polyamine toxin affected the NMDA, kainate or AMPA response without the presence of the respective agonist.

Animals

Characterization of the papain active centre by using two-protonic-state electrophiles as reactivity probes. Evidence for nucleophilic reactivity in the un-interrupted cysteine-25-histidine-159 interactive system.

1.2,2'-Dipyridyl disulphide (2-Py-S-S-2-Py) and n-propyl 2-pyridyl disulphide (propyl-S-S-2-Py) were used as two-protonic-state reactivity probes to investigate the active centre of papain (EC 3.4.22.2).2. The existence of a striking rate optimum at pH approx. 4 in the reaction of papain not only with the symmetrical probe but also with the unsymmetrical probe is shown to constitute compelling evidence that the thiolate ion component of the cysteine-25-histidine-159 interactive system of papain possesses appreciable nucleophilic character. It is not a necessary requirement that the probe reagent should engage the imidazolium ion of histidine-159 in hydrogen-bonding for the sulphur atom of the interactive system to display nucleophilic character. The single proton-binding site of propyl-S-S-2-Py cannot simultaneously interrupt the active-centre ion pair and provide for rate enhancement as the pH is lowered towards 4. The possible implication of this for the mechanism of papain-catalysed hydrolysis is discussed. 3. The suspected difference in the active centres of papain and ficin (EC 3.4.22.3), which could be a lack in ficin of a carboxy group conformationally equivalent to that of aspartic acid-158 of papain is confirmed. The reactivity of the papain thiol group towards both probe reagents is controlled by two ionizations with pKa close to 4 that are positively co-operative. 4. In the reaction of papain with 2-Py-S-S-2-Py. the reactivity appears to be controlled also by an addition ionization with pKa approx. 5. Possible origins of this additional ionization are discussed. K. The spectral and ionization characteristics of propyl-S-S-2-Py are reported. 6. The reagent reacts rapidly with thiol groups at the sulphur atom distal from the pyridyl ring to provide, at pH values below 9, stoicheiometric release of 2-thiopyridone. This property, together with the ability of the reagent markedly to increase its electrophilicity consequent on protonation, suggests alkyl-2-pyridyl disulphides in general as valuable two-protonic-state reactivity probes with exceptional specificity for thiol groups.

2,2'-Dipyridyl

Treatment of infected un-united femoral shaft fractures.

Twenty patients treated for osteomyelitis following intramedullary fixation of fractures of the femoral shaft were assessed from the standpoint of antibiotics, internal fixation, drainage, sequestrectomy and external support. Analysis of intramedullary fixation in the form of Küntscher nailing with respect to the rate of union, duration of treatment and number of operative procedures, suggests that rigid intramedullary fixation is superior to plates and screws and plays an important role in development of union in the presence of infection.

Adolescent

Un-united fracture of the scaphoid.

The anterior approach as described by Matte and Russe for treatment of ununited fractures of the scaphoid was employed in 48 patients using autologous cortical cancellous pegs and chips. Operative intervention occurred in an average period of 14 months after fracture. The average time to radiological union was 3.5 months; the average follow-up was 2 years. Union occurred in 43 patients. The anterior approach is recommended because of its simplicity. Neither avascular necrosis nor a small proximal pole fragment are contraindications to the procedure.

Carpal Bones